PMID- 9633405
TI - Hungry for peace.
PMID- 9633406
TI - Nurses who blow he whistle need more support.
PMID- 9633407
TI - Vile bodies.
PMID- 9633408
TI - Priceless.
PMID- 9633409
TI - Taking effect.
PMID- 9633410
TI - Taking the lead.
PMID- 9633412
TI - The great escape.
PMID- 9633411
TI - Florence revisited.
PMID- 9633413
TI - Men: the hidden crisis.
PMID- 9633414
TI - Will two become one?
PMID- 9633415
TI - Hearing aid.
PMID- 9633416
TI - To err is human to forgive is divine, as one nurse found out.
PMID- 9633417
TI - Clinical supervision: what's going on? Results of a questionnaire.
AB - This paper presents data obtained from a questionnaire sent to trust nurse
executives in England and Scotland. While the data indicates a great deal of
enthusiasm for clinical supervision, some concern must be shown for the lack of
preparation and support for those involved in its implementation, a fact that
will undoubtedly reflect badly in any evaluation exercise.
PMID- 9633418
TI - Major incidents at large sporting venues.
PMID- 9633419
TI - A behavioural approach to obsessive compulsive disorder.
PMID- 9633421
TI - Reducing risks in lifting and handling.
PMID- 9633420
TI - Managing systemic lupus erythematosus.
PMID- 9633422
TI - Thoroughly modern leaders.
PMID- 9633423
TI - It's tough at the top.
PMID- 9633424
TI - Climbing frame.
PMID- 9633425
TI - [The concept of paradigm in nursing science].
AB - This paper critically analyses the use of the term paradigm in nursing science.
The essay consists of two main sections. The "prekuhnian" meaning of the paradigm
term is described in the first section. The developments in the philosophy of
science are presented in conjunction with the rise of the "antipositivist turning
point" and Kuhn's historical approach with its central terms (paradigm,
revolution, normal science). Some central points of criticism regarding Kuhn's
approach close the first section. The second section gives attention to the
application of the term paradigm in nursing science, at first describing the
situation in the USA and subsequently referring to Germany. The insufficient
extent of discussions on questions and problems regarding the philosophy of
science is elucidated in the following criticism. The examination comes to the
conclusion that the application of the paradigm term to nursing science is
neither possible nor is it sensible. A brief review of the prospects for nursing
science concludes the essay.
PMID- 9633426
TI - [Reading: a source of information. Study of motivational factors, influencing the
reading of professional literature in nursing].
AB - A qualitative research among 13 Dutch nurses working in different areas of
nursing investigated which factors might influence nurses' motivation (not) to
read specialist literature. Two central subjects were identified: nurses'
personal interests and the influence of the environment at work. Analysis of the
data shows a great influence of the work environment on the individual nurse's
choice to read specialist literature: the more stimulating the environment is
towards developing and discussing knowledge, the more nurses make use of
specialist literature. An individual reason to consult such literature is formed
by the presence of "search questions", based on incidents in a person's actual
work situation. Informants report little or no interest in research or studies:
they only incidentally read abstracts of research findings, and only concerning
subjects directly linked with their own practice situation. Influence of the work
environment seems to play an important role on the choice made.
PMID- 9633427
TI - [Disruptive behavior of elderly residents and the use of nursing methods].
AB - This study is the first part of a larger research project concerned with
disruptive behaviour and the use of physical restraints on elderly nursing home
residents. This paper is focused on the types and prevalence of disruptive
behaviour among elderly residents, nurses' experiences and the types of nursing
interventions employed. Data was collected from nurses of varying qualifications
(n = 173) in seven Swiss nursing homes by using a questionnaire. The most
frequent behavioural problems reported by nurses were mobility, incontinence,
getting dressed, verbal communication, passivity, withdrawal and continual
requests. Nurses found physical aggression, continual shouting and verbal abuse
the most difficult to manage with. The results also indicated that experiences
varied between nurses. In particular, nursing staff always considered disruptive
behaviour more disruptive against other residents rather then against themselves.
The most frequently used interventions against disruptive behaviour were
considering residents' wants and needs, getting close, adjustment to residents'
background and organisation of activities. Physical and chemical restraints were
also used.
PMID- 9633428
TI - [Eating and drinking in patients with Alzheimer dementia. A study of
interactions].
AB - Eating and drinking become difficult for people afflicted with dementia. We have
therefore analysed the mealtime constellation in five cases of institutionalised
people suffering from Alzheimer using video in an open technique. The process of
eating and drinking entailed intensive interaction between patients and their
nurses. The demented were apparently in possession of extensive nonverbal
communicative ability to both transmit and receive signals. It proved possible to
identify behavioral factors that hinder or benefit the mealtime procedure of the
analysed cases.
PMID- 9633429
TI - [Decisions and attitudes of nurses in the care of chronically ill elderly
patients].
AB - Data of 182 nurses from two teaching hospitals regarding their attitudes to
determinants of the decision-making process in elderly patients in general and
decisions in the treatment of an moderately demented, incompetent elderly man
with a potentially reversible life-threatening illness using a scenario were
analyzed. 68.1 percent complied to the patient's will when an advance directive
existed. One fifth reported that the patient's directive was supportive for the
decision. The more important the wishes of the patients were evaluated, the more
frequent a less aggressive treatment choice was preferred and the less frequent
the decision was for resuscitation in the case of a cardiac arrest. The increased
use of advance directives is desirable to reduce the number of conflicts in
decision-making for healthcare professionals and to reduce the patients' fears of
over- or undertreatment and for increasing their possibilities of self
determination. A more intensive integration of topics such as death and dying,
treatment of the chronically ill elderly as well as possibilities and limitations
of patient directives and their use in the education of nurses is required.
PMID- 9633430
TI - [Expectations of the nursing profession at the beginning of nursing education and
their realization at the end of the 2 year (longitudinal study)].
AB - When young people start a career in nursing, they have certain expectations about
the profession. The intrinsic motivation of wanting to help plays the most
important role. Does the nursing profession actually fulfill these expectations
or will the everyday-routine of the profession soon disappoint the students? In
the study presented, 166 nursing students were tested twice, once at the
beginning of their education (Veit, 1996) and after having completed their second
year of training. The comparison of the results of both surveys enables us to
determine to which extent the expectations connected with the choice of a career
were actually fulfilled. On the whole, the students participating in the survey
were satisfied with their career choice. The degree to which their expectations
were fulfilled, however, vary according to the different groups of students.
PMID- 9633431
TI - [When antiquated methods change].
PMID- 9633432
TI - [50 years of Pflegezeitschrift. "Contemplations on the restlessness of everyday
life"].
PMID- 9633433
TI - [The owner of an old-age home defends himself against the dictates of the nursing
insurances: the new culture of assistance before the Kadi].
PMID- 9633434
TI - [Introducing juridic opinion for the nursing profession: the opinion is marking
the entrance into the labyrinth of the juridic system].
PMID- 9633436
TI - [Conference "Hommage to Sister Liliane Juchli in Kassel/Baunatal: "Harness your
chariot to the stars"] [In Process Citation]
PMID- 9633435
TI - [The neonatologic intensive care unit at the Stuttgart Olga Hospital. A cheerful,
childlike outfit next to extensive high-tech equipment].
PMID- 9633437
TI - [Microbial infections from the water bottle: still waters can give you a
bellyache].
PMID- 9633438
TI - [Local anesthetics and their use: special anesthetic measures are available for
the extremities].
PMID- 9633439
TI - [Sexuality and disease: sometimes taboos are broken].
PMID- 9633440
TI - [Surgical interventions in the aged. 1. Old age is no contraindication].
PMID- 9633441
TI - [The unit work place, supported by electronic data processing: which requirements
do hardware and software have to meet?].
PMID- 9633442
TI - [Evaluation of co-workers. 2. Sources of error must be recognized and avoided].
PMID- 9633443
TI - [Quality features and standards for personnel developing measures:
interprofessional discipline and professionality are the focus].
PMID- 9633444
TI - [Professional fatigue: a review of literature and implications for nurses].
AB - The objective of this paper is to present literature revision of the factors
which contribute to the professional hospital nurse fatigue. Burnout Syndrome,
which is specific of the professionals who work directly with clients, like the
hospital nurses, was chosen as a focus of study. The Burnout Syndrome is
characterized by three fundamental symptoms: the sentiment of emotional fatigue,
personal withdrawal and the reduction of professional achievement. In addition,
the main associate variables were studied, and grouped in three categories:
personal, organization and the work structure variables.
PMID- 9633445
TI - [Notes about the historical evolution of health policies in Brazil].
AB - This paper is an historical review of the health policy in Brazil. Ranged since
the arrival of the real portuguese family to Brazil until nowadays. The review
intent to contextualize present facts based on historical, social and political
facts for the needed foundation to give best comprehension of the ways in which
is organizing the health policy in Brazil.
PMID- 9633446
TI - [Relationship between gender and holistic representations of health and illness].
AB - The article examines the relations that may exist between gender and holistic
representations of health and illness having medicine flower as approach's
parameter. It presents a short traditional medicine history and the appearance of
alternative therapeutic practice. By understanding gender like a process of
social construction it suggests a theoretical account proposition that explains
the majority presence of women between users and flower therapists.
PMID- 9633447
TI - [Paternity in the perspective of a group of fathers].
AB - Looking upon occidental silence which involves the paternity, we performed this
research with the intention to conceive some associated aspects: the family role,
birth of son expectation and father social role. For that, 7 fathers have been
interviewed with ages between 21 and 45 years. This study allowed us observed
that the paternity of the interviewed fathers is experienced by the father-son
relationship preoccupation, kids education and the constant search of ways to
experience the paternity as a form to be near of the kids and the wife.
PMID- 9633448
TI - [How nurses evaluate home nursing and family caregivers].
AB - The aim of this study was to assess the way used by nurses for evaluate the
family care and the caregiver. The method used was a quali-quantitative one. A
semi-structure interview was the instrument chosen to collect data. It was
applied to 20 (twenty) nurses from a University Hospital within the months of
April and May, 1996. Data analysis was based on the Bardin's Content Analysis
Technique (1994). The results demonstrated that nurses are not systematic in
evaluating family care and the caregiver, but they use their intuition, based on
momentaneous decisions. This reveal a difficulty of integration between the
formal and the informal care caused by lack of interaction or effective
valorization of the family care process.
PMID- 9633449
TI - [Professional fatigue: empirical study with hospital nurses].
AB - This is a empirical approach about professional fatigue of the hospital nurse.
The fatigue concept was based on the Burnout Syndrome and some hospital variables
associated. The sample consisted of 341 nurses of whom demographic data is
available. Results of the application of the psychometric analysis of Burnout
Inventory, as well as statistic correlation between the three scales and
demographic data are presented. Considerable presence of emotional exhaustion and
cognitive weariness as a consequence of the working atmosphere in the hospital
critical sectors and the nursing chief responsibility were found.
PMID- 9633450
TI - [Students opinion about the administration of adult assistance].
AB - This article describes the student's opinion about the discipline Administration
of Adult Nursing Assistance, developed in the 7th term of nursing graduation
course in UFRGS Nursing School. The aspects evaluated were: organization,
objectives, theoretical framework, subjects relevance, teaching strategies, field
of practice learning and supervision. It's a qualitative study, the instrument
used is a questionary with open questions, which allows the students write their
points of view about the discipline. The population selected was all students of
7th term of course in 1996/1 and 1996/2 (77 students), but only 34 students
answered the instrument. The data were analyzed by Bardin (1977) conteud analysis
approach.
PMID- 9633451
TI - [Violence: a social ill or the coded expression of an expectation].
PMID- 9633452
TI - [Aggression, violence, how to deal with them].
PMID- 9633453
TI - [The violent interlocutor and the professional].
PMID- 9633454
TI - [Institutional policies on violence].
PMID- 9633455
TI - [The Public Assistance--Hospitals of Paris: an institution fighting violence.
Interview by Isabelle Levy].
PMID- 9633456
TI - [Violence in psychiatric emergencies. Improving and making the best of the care
of a violent patient].
PMID- 9633457
TI - [Violence as a counter attitude].
PMID- 9633458
TI - [Establishment of accreditation. The patient's expectations].
PMID- 9633459
TI - [A booklet on patient admission in ophthalmology].
PMID- 9633460
TI - [In order to be happy, let us relax].
PMID- 9633461
TI - [Esthetic care in a Center for the Fight Against Cancer].
PMID- 9633462
TI - [The responsibility of nursing students within the facilities who accept them
during their training].
PMID- 9633463
TI - [Effects of drug distribution, entero-hepatic cycle, bioavailability].
PMID- 9633464
TI - [Critical ischemia of the legs and vascular rehabilitation. Holistic care].
PMID- 9633465
TI - [Nursing spring. Seasonal temperatures lower than normal].
PMID- 9633466
TI - [Parkinson's disease].
PMID- 9633467
TI - [Falls in the elderly].
PMID- 9633468
TI - [Psychogeriatric emergencies in the general hospital].
PMID- 9633469
TI - [Glaucoma in the elderly].
PMID- 9633470
TI - [Treatment of malnutrition].
PMID- 9633471
TI - [The Program for Medical Information Systems. After care or rehabilitation.
Example of organization in a geriatric services].
PMID- 9633472
TI - [Familiarity in addressing institutionalized patients].
PMID- 9633473
TI - [Dementia, memory and identity].
PMID- 9633474
TI - [The team is like a living being].
PMID- 9633475
TI - [Preparing a meal. Improving the utensils].
PMID- 9633476
TI - [Psychomotor practice in geriatric psychiatry].
PMID- 9633477
TI - [Living places. Admission of the elderly into families].
PMID- 9633478
TI - [Malaise in newborns].
PMID- 9633479
TI - [Gastroesophageal reflux. Nursing surveillance].
PMID- 9633480
TI - [Gastroesophageal reflux. pH measurement].
PMID- 9633481
TI - [Gastroesophageal reflux. Surgical treatment using laparoscopy. Indications and
principles].
PMID- 9633482
TI - [Gastroesophageal reflux. Pre- and postoperative care].
PMID- 9633483
TI - [Psychological stress of professionals].
PMID- 9633484
TI - [The temptation of a sacrificial position].
PMID- 9633485
TI - [Tracheotomy and nursing care in children].
PMID- 9633487
TI - [Rowing against stress].
PMID- 9633489
TI - Technological infusion! Medical diffusion. Personal confusion?
PMID- 9633488
TI - [Secure plan in maternity hospitals].
PMID- 9633490
TI - The role of video-assisted vascular surgery.
PMID- 9633491
TI - A scoring system to predict the outcome of long femorodistal arterial bypass
grafts to single calf or pedal vessels.
AB - OBJECTIVES: The aim of this study was to develop a scoring system to predict the
outcome of long femorocrural and femoropedal bypass grafts performed for critical
limb ischaemia. SETTING: Teaching hospital. METHODS: An analysis of 109
consecutive femorodistal bypass grafts performed for critical lower limb
ischaemia between June 1991 to December 1994. Factors shown to affect the outcome
were: inflow, number of patent calf vessels, graft material, straight flow to the
foot and patent pedal vessels. These variables were weighted according to their
relative significance (multivariate Cox regression) and a scoring system (ranging
from 0 to 10) was developed. RESULTS: Patients with a preoperative score of 0-4
(n = 35) showed a secondary patency of 36% at 1 month, 12% at 3 months and 0% at
10 months (Cum SE = 6.90/0.0). Secondary patency rates for the 46 patients with
score 5-7 were 88.7% at 3 months, 56.3% at 12, and 45.1% at 2 and 3 years (Cum SE
= 9.82), while the respective values for the 28 patients with score 8-10 were
92.7%, 88.5% and 81.7% (Cum SE = 8.08). The difference was highly significant (p
= 0.000) in all tests of equality. In addition, the median total hospital cost
was 12,600 Pounds for the group 0-4 compared with 8100 Pounds (group 5-7) and
4400 Pounds (group 8-10) (p = 0.0085). CONCLUSIONS: This preoperative scoring
system appears to correlate well with the outcome of distal revascularisation to
single calf or pedal vessels. If applied to patient selection, it could
significantly reduce the total hospital cost per leg saved. A prospective testing
of its predictive ability is needed and is in progress.
PMID- 9633492
TI - Intraoperative high resolution duplex imaging during carotid endarterectomy:
which abnormalities require surgical correction?
AB - OBJECTIVES: This study evaluates high resolution, duplex ultrasound imaging for
quality control of carotid endarterectomy in order to determine which technical
factors were linked to residual stenosis and to define duplex criteria for re
exploration. DESIGN, MATERIAL AND METHODS: A consecutive series of 100 patients
undergoing carotid endarterectomy were evaluated. Duplex imaging was performed
prior to wound closure and repeated at 6-8 weeks postoperatively. Stenoses were
classified as non-significant, moderate or severe based on duplex criteria.
Intimal flaps, shelves, kinks, clamp damage and fronds were identified by
ultrasound imaging. RESULTS: Five moderate stenoses were noted in the proximal
endarterectomy site (PES), and at follow-up three had resolved. Adherent fronds
were detected in 83% of vessels and resolved in all but three cases. At the
distal endarterectomy site there were 10 severe and 12 moderate stenoses. Intimal
flaps were associated with an increased incidence of residual stenosis (p =
0.010). CONCLUSIONS: We conclude that severe stenoses with an intimal flap should
be corrected immediately. Further data is required to establish the significance
of kinks. Residual intimal flaps in the PES appear to remodel. The role of
completion duplex may lie in the modification of surgical technique to eradicate
anatomical and haemodynamic imperfections.
PMID- 9633493
TI - The progression and correction of duplex detected velocity shifts in
angiographically normal vein grafts.
AB - OBJECTIVES: To review the sensitivity of duplex scanning and angiography at
detecting vein graft stenoses in patients on a graft surveillance programme.
DESIGN: Prospective, open, non-randomised study. PATIENTS AND METHODS: Since
February 1993, 143 patients with 148 grafts (70% in situ, 30% reversed) have
attended postoperative infrainguinal vein graft surveillance for a minimum of 6
weeks. Fifty-seven graft stenoses in 57 grafts were identified by duplex scanning
as a localised high velocity jet. Angiography was performed in all except 12
patients. RESULTS: Angiography confirmed a duplex abnormality in all but 10
patients. Of these, five patients remain stable and asymptomatic with a
persisting duplex abnormality. The remaining five patients, although
asymptomatic, exhibited disease progression on duplex and surgical intervention
confirmed significant stenoses, which were successfully treated. CONCLUSION: The
results suggest that duplex scanning is a reliable imaging modality for detecting
vein graft stenoses. Selection for surgical correction can be made, in some
circumstances on the basis of clinical and ultrasound criteria alone.
PMID- 9633494
TI - Postoperative fever, bowel ischaemia and cytokine response to abdominal aortic
aneurysm repair--a comparison between endovascular and open surgery.
AB - OBJECTIVES: To study bowel ischaemia in transfemorally placed endoluminal
grafting (TPEG) for abdominal aortic aneurysms, and any relation to cytokine
response or postoperative fever. DESIGN: Prospective not randomised. University
hospital setting. MATERIAL: Fourteen cases of conventional surgery and 23 cases
of endovascular technique for infrarenal abdominal aortic aneurysm repair.
METHODS: Tonometry was used for sigmoid colon pH, and ELISAs for serum IL-6.
RESULTS: Mucosal pH in the sigmoid colon fell significantly during clamping and
reperfusion in both groups. Lowest measured sigmoid colon pH was 7.10 in the open
group, compared to 7.22 in the TPEG group (p < 0.05). The IL-6 levels in serum
peaked after 4 h of reperfusion; 249 pg/ml in the open group, compared to 89
pg/ml in the TPEG group (p < 0.05). High levels of IL-6 in the postoperative
period and persisting low sigmoidal pH were associated with serious
complications. Postoperative temperature did not differ significantly between the
groups, and no significant correlation could be found with sigmoid colon pH or IL
6 levels. CONCLUSIONS: The less pronounced perioperative bowel ischaemia in TPEG
patients indicates an advantage of the TPEG technique. Splanchnic ischaemia was
not related to postoperative fever, nor the IL-6 or TNF response.
PMID- 9633495
TI - Importance of graft configuration in outcome of endoluminal aortic aneurysm
repair: a 5-year analysis by the life table method.
AB - AIM: The aim of this study was to determine the influence of graft configuration
on the outcome of endoluminal repair of abdominal aortic aneurysm (AAA). METHODS:
The 5-year study period extended from May 1992 to May 1997 and included analysis
of patients undergoing endoluminal AAA repair in the first 4.5-year period with a
minimum follow-up period of 6 months. Between May 1992 and November 1996 136
patients underwent endoluminal AAA repair. Two patients who had endoluminal
repair of anastomotic AAA and six patients who had secondary endoluminal repair
of AAA were excluded, leaving 128 patients in the study group. There were 117
males and 11 females with a mean age for the group of 71 years. The configuration
of the grafts was tubular aortic (T) (n = 50), tapered aortoiliac/femoral (AI) (n
= 24) and bifurcated (B) (n = 54). Patient characteristics and co-morbidities
were similar in the three groups. The procedures were performed in the operating
room under radiographic control. Follow-up was complete and consisted of regular
physical examination and contrast enhanced computed tomography. Outcome measures
were perioperative mortality rate, need for conversion to open repair, presence
of early and late endoleaks, successful exclusion of AAA from the circulation,
and survival. Data were analysed by the life table method. RESULTS: There was no
significant difference in perioperative mortality for T (4%), AI (4%) and B
(5.5%) configuration of endograft. Outcome for T, AI, and B configurations was
respectively: primary conversion (%) 8, 12, 13; early endoleaks (n =) 5, 0, 1;
late endoleaks (n =) 7, 0, 1. The overall incidence of failed procedures
throughout the study period was higher in tube grafts compared with non-tube
(aortoiliac and bifurcated) grafts (p < 0.05). Kaplan-Meier curves demonstrated a
success probability at 40 months of 50% for tube grafts and 80% for non-tube
grafts. However, a comparison of the time to procedure failure between tube
versus non-tube after adjusting for competing risks (death without prior graft
failure) was non-significant (p = 0.14). CONCLUSIONS: The poor mid-term outcome
for tube prostheses requires a reassessment of the criteria for selecting this
configuration. It would be unwise to abandon the use of tube prostheses entirely
in endoluminal repair. With increasing information on mid and long-term outcome
of endoluminal AAA repair it is likely that there will be an increasing
acceptance of treating smaller AAA while they are still suitable for treatment by
the endoluminal method and most likely with tube grafts. A tightening of the
criteria for using tube prostheses would seem sensible. In particular, the
minimum length of distal neck required for endoluminal tube graft repair should
be increased to the 2-2.5 cm range.
PMID- 9633496
TI - Clinicopathological evidence that neovascularisation is a cause of recurrent
varicose veins.
AB - OBJECTIVES: Recurrent varicose veins may result from poor initial surgical
technique or progression of varicosities in collateral veins. In some cases new
veins may develop at the saphenofemoral junction (neovascularisation) and cause
recurrent saphenofemoral incompetence. This was a histological study of recurrent
varicose veins. DESIGN: This clinicopathological study included 20 patients
(median age 55 years) who had surgery for recurrent saphenofemoral incompetence.
MATERIALS AND METHODS: A total of 28 legs had groin re-exploration with repeat
flush saphenofemoral ligation. The venous tissue block from the saphenofemoral
region (including the proximal thigh varicosity) was excised and orientated for
histological analysis. Evidence of neovascularisation was sought using routine
histological sections and S100 immunohistochemistry. RESULTS: At operation, thin
walled, serpentine neovascular veins were detected clinically as the principal
cause of recurrence in 19 groins. In five groins recurrence was due to a residual
missed vein at the saphenofemoral junction, and in four recurrence was caused by
cross groin collaterals. On histological sections, evidence of neovascularisation
was present in 27 of 28 groins. In eight it co-existed with the veins missed at
the original operation but it was the sole identified cause of recurrent
saphenofemoral incompetence in 19 (68%) groins. CONCLUSIONS: Neovascularisation
was the principal cause of recurrent saphenofemoral incompetence in this series.
PMID- 9633497
TI - Physical and mechanical properties of ePTFE stretch vascular grafts determined by
time-resolved scanning acoustic microscopy.
AB - OBJECTIVES: Determination of physical and mechanical characteristics and
properties of thin-walled (0.39 mm) expanded polytetrafluoroethylene stretch
vascular prostheses by time-resolved scanning acoustic microscopy (TR-SAM).
MATERIALS AND METHODS: Samples of Stretch Gore-Tex were mounted on
polymethylmethaacrylate substrate, and ethyl alcohol was used as acoustic
couplant. A 10 MHz ultrasound transducer mounted on a SAM50 scanning acoustic
microscope generated short, pulsed sound waves. Reflected signals were used for
imaging and for computer analysis of time resolved wave forms acquired by a
digital sampling oscilloscope to calculate physical and mechanical
characteristics of the material. RESULTS: Graft wall thickness: 0.395
(0.352/0.401) mm; graft wall sound wave penetration velocity: 1111 (1083/1129) ms
1; acoustic impedance: 3.685 (2.975/4.370) 10(6) kg m-3s-1; attenuation
coefficient: 0.144 (0.096/0.229) dB mm-1 MHz-1; material density: 3360
(2712/3982) kg m-3; elastic stiffness: 4.06 (3.35/4.83) GPa (median and (25/75)
percentiles; n = 8 samples, 10 measurements spaced 100 microns apart in each
sample). CONCLUSIONS: TR-SAM can effectively quantify ePTFE graft wall
properties, and new data on graft properties have been provided. The acoustic
impedance and elastic stiffness of the ePTFE graft wall are 2.2 and 1.6 times
higher, respectively, than in human coronary arteries, and it is highly
reflective of ultrasound.
PMID- 9633498
TI - Early carotid endarterectomy after non-disabling ischaemic stroke: adequate
therapeutical option in selected patients.
AB - OBJECTIVE: To evaluate neurological outcome and long-term results of early
carotid endarterectomy (CEA) after non-disabling stroke. MATERIALS: Retrospective
study between 1980 and 1995 of 56 patients undergoing CEA within 4 weeks of a
transient (n = 15) or a permanent non-disabling (n = 41) ischaemic stroke.
METHODS: Analyses of preoperative cerebral CT imaging, neurological outcome (mod.
Rankin-scale) and long-term results (life-table analyses according to Kaplan
Meier). RESULTS: Incidence of early CEA increased from 1.7% (27 out of 1636) in
the period 1980-1993 to 7.8% (29 out of 374) between 1994 and 1995. CEA was
indicated after a neurological plateau phase was established (median interval 14
days). Fifty-seven per cent of the CEA patients had a minor ischaemic infarction
(area < 2 cm), 18% showed a large territorial ischaemic infarction (area 2-5 cm)
in cerebral CT imaging. Two patients deteriorated postoperatively (minor stroke
rate 4%) but no major stroke or death occurred. Life-table probability of stroke
free survival (mean follow-up 42.7 months) was 94%, 90% and 84%, respectively,
after 1, 2 and 5 years. Kaplan-Meier survival rates were 96%, 91% and 86% after
1, 2 and 5 years. CONCLUSIONS: Early CEA after non-disabling stroke is a safe
procedure in selected patients.
PMID- 9633499
TI - A seasonal variation in the incidence of ruptured abdominal aortic aneurysms.
AB - OBJECTIVE: To discover whether there is a seasonal variation in the incidence of
rupture of abdominal aortic aneurysms. DESIGN: Deaths per month due to rupture of
abdominal aortic aneurysm were analysed retrospectively using a cosinor
regression model. SETTING: England and Wales. SUBJECTS: 19,599 patients who died
from rupture of abdominal aortic aneurysm between January 1991 and December 1995
according to death certification data. INTERVENTIONS: None. RESULTS: A seasonal
variation in the incidence of rupture of abdominal aortic aneurysm occurs, with a
peak in winter (p = 0.003). The ratio of rupture of abdominal aortic aneurysm in
males and females decreased from more than 12 to 1 below age 60 years to less
than 5 to 1 over age 80 years. CONCLUSIONS: There is a seasonal variation in the
incidence of recorded deaths from abdominal aortic aneurysm in England and Wales,
with a peak of deaths in the cold winter months. The underlying cause is unknown,
but hypertension and tobacco smoking are predisposing factors to aortic aneurysm
rupture. Exposure to tobacco smoke is known to be greater indoors in cold weather
and there is a winter peak of blood pressure in hypertensive patients.
PMID- 9633500
TI - Economising vein-graft surveillance programs.
AB - OBJECTIVES: To investigate the effectiveness of two alternative vein-graft
surveillance strategies. In the first strategy surveillance was restricted to
patients with a possible higher risk of significant stenosis development, i.e.,
those with a moderate stenosis identified early after the operation. In the
second strategy the effects of reducing the number of duplex tests per patient
was examined. PATIENTS AND METHODS: In a prospective study in three vascular
surgical departments 300 patients (300 femoropopliteal or distal grafts)
underwent duplex surveillance during the first year after the operation. The
duplex-derived PSV-ratio was considered to represent the degree of stenosis.
Arteriographic confirmation of suspected stenoses was routinely obtained, and
patients without a suspected graft stenosis underwent a consented arteriogram
during the first postoperative year. The decision to perform a graft revision was
taken on the basis of an arteriographic stenosis of at least 70% diameter
reduction. In the first strategy graft categories were defined on the basis of
the first postoperative duplex examination: grafts with a PSV-ratio < 1.5, grafts
with a PSV-ratio < 1.5-2.0, grafts with a PSV-ratio of 2.0-2.5, grafts with PSV
ratios 2.5-3.0, and grafts with PSV-ratios > 3.0. The primary patency rate at 12
months was compared for these categories. In the second alternative strategy the
number of examinations and the percentage of event causing de novo stenoses were
analysed per surveillance interval. RESULTS: The presence of moderate
abnormalities at the initial duplex scan did not identify patients with a high
risk of an event, as initial PSV-ratios of 1.5-2.0 and 2.0-2.5 (early mild
moderate lesions) had comparable 12-month primary patencies to patients with a
PSV-ratio < 1.5 (completely normal grafts): (63%, 73%, and 71%, respectively).
The interval incidence of event causing de novo stenoses was 8% of the total
number of duplex tests performed at 3 months, and 8% at 6 months after the
operation. In patients who had no previous intervention for stenosis and had a
normal bypass during the first 6 months postoperatively, a sharp drop in this
incidence was seen at 9 and 12 months, with event causing de novo stenoses
observed in only 2% and 1% of all duplex tests. CONCLUSIONS: All patients should
be included in a surveillance program, as the presence of a normal vein graft at
the first duplex examination does not rule out the subsequent development of
graft stenosis. The duration of the surveillance period may be restricted to the
first 6 months after operation in patients who have a normal bypass during that
time period, as only few stenoses will be missed by this policy.
PMID- 9633501
TI - Management of iliac occlusions with a new self-expanding endovascular stent.
AB - OBJECTIVES: To determine the patency and acceptability of the Memotherm
endovascular stent in the treatment of iliac arterial occlusions. MATERIALS AND
METHODS: Twenty-two patients (12 males and 10 females) underwent stenting of
iliac occlusions of the aortoiliac bifurcation, the common iliac artery and the
external iliac artery. All patients were reassessed at 3, 6 and 12 month
intervals and then yearly to evaluate their symptoms and Doppler pressure
measurements. Comparison was made with results from other studies treating iliac
occlusions by angioplasty alone or combined with stenting. RESULTS: Out of 22
patients, 21 had an immediate and sustained improvement over the whole of the
follow-up period. The Ankle-brachial Index (ABI) increased from a mean value of
0.49 to 0.81 3-months postprocedure and improved to 0.85 at 12 months (paired t
test p < 0.001). At 6 and 12 months the stent patency remained at 95.5%, which
compares favourably with other studies. There were four minor and one major
complication associated with the stenting procedure. CONCLUSIONS: The Memothern
self-expanding stent is a useful, safe and effective device suitable for the
majority of iliac occlusions. Further long-term evaluation is warranted to
confirm its advantages over open surgery.
PMID- 9633502
TI - Venous allografts prepared from stripped long saphenous vein. Is there a need for
antibiotic sterilisation?
AB - AIM: Can useful lengths of vein be retrieved from varicose vein stripping
procedures; is it necessary to sterilise this tissue prior to use as vein
allografts? METHOD: Stripped long saphenous vein was retrieved at operation. Vein
samples were cultured using direct plate inoculation and enrichment culture.
Further samples were immersed in two low concentration antibiotic solutions and
recultured. Smooth muscle viability was assessed after antibiotic immersion and
storage by cryopreservation. RESULTS: High quality vein could be retrieved by
vein stripping. Vein segments grew skin commensals on enrichment culture despite
negative cultures with standard media plate inoculation (Chi-squared = 53.34 1
d.f. p < 0.001). Low concentration antibiotic solutions sterilised processed
vein. Smooth muscle cell viability was reduced by cryopreservation, Mann-Whitney
p = 0.008 (control 98% S.E. 0.93 vs. cryopreserved 64% S.E. 6.58), but prior
exposure to antibiotics did not compound this effect. CONCLUSION: Useful lengths
of vein grafts can be retrieved from varicose vein stripping procedures. Venous
segments are frequently contaminated by skin commensals. Enrichment culture is
required to detect contamination. Low concentration antibiotics sterilise venous
tissue without affecting smooth muscle cell viability.
PMID- 9633503
TI - Polytetrafluoroethylene (PTFE) femorodistal grafts with a distal vein cuff for
critical ischaemia.
AB - OBJECTIVE: To analyse the results of PTFE femorodistal bypass grafts using a
distal anastomotic vein cuff in the treatment of critical ischaemia. DESIGN:
Prospective study of consecutive patients under the care of a single Vascular
Surgeon. SETTING: A dedicated Vascular Surgical Unit in a University teaching
hospital. SUBJECTS: Fifty-one consecutive femorodistal PTFE grafts were performed
on 50 patients (median 74 years, range 58-94 years, 25 men; median ankle:brachial
index 0.4). In 28 (55%) a common ostium arteriovenous fistula (AVF) was fashioned
at the distal anastomosis. RESULTS: The 30-day postoperative mortality was 8%,
with 10 (21%) major complications. The 1 and 2 year primary patency was 64% and
51%, respectively, with corresponding limb salvage rates of 85% and 80%. The
presence of an AVF did not significantly affect graft patency or patient
survival, but appeared to hinder limb salvage. The latter effect may be due to
bias in patient selection. CONCLUSION: PTFE femorodistal grafts with a distal
vein cuff are a suitable alternative to autogenous saphenous vein in distal
reconstructions for critical ischaemia. No conclusions can be made about the
efficacy of an AVF in this context.
PMID- 9633504
TI - Primary repair of ruptured aortitis.
PMID- 9633505
TI - Cystic adventitial disease.
PMID- 9633506
TI - A superficial femoral artery aneurysm in a patient with Marfan's syndrome.
PMID- 9633507
TI - Superficial femoral artery mycotic aneurysm following appendicectomy.
PMID- 9633508
TI - Sequential progression of the differentiation program by bone morphogenetic
protein-2 in chondrogenic cell line ATDC5.
AB - During embryonic development of long bones, chondroprogenitor cells exhibit the
transitions of phenotype, i.e., from type I collagen-expressing cells to type II
collagen-expressing chondrocytes through cellular condensation (early-phase
differentiation) and then to type X collagen-expressing mineralizing chondrocytes
(late-phase differentiation). The chondrogenic cell line ATDC5 displays the
sequential transitions of phenotype in a synchronous manner in vitro. Taking
advantage of the sequential differentiation, the effects of growth factors were
evaluated at each differentiation step of ATDC5 cells. Among the factors
examined, bone morphogenetic protein-2 (BMP-2) specifically stimulated a
progression of the early-phase differentiation. Rounded chondrocytic cells were
formed all over the culture plates by skipping out a cellular condensation stage.
Fibroblast growth factor-2 stimulated growth of undifferentiated ATDC5 cells, but
failed to stimulate overt chondrogenesis. The proliferation of differentiated
cells ceased as cartilage nodules became maturated. At this stage, BMP-2 markedly
up-regulated expression of type X collagen mRNA (a 9.1-fold increase) and
alkaline phosphatase mRNA (a 7.5-fold increase) within 48 h. On the other hand,
it down-regulated expression of type II collagen and parathyroid hormone
(PTH)/PTH-related peptide (PTHrP) receptor mRNAs, markers of the early
differentiation. BMP-2 stimulated the formation of calcified matrix, an end
product of terminally differentiated chondrocytes. These results indicated that
BMP stimulated the sequential progression of early- and late-phase
differentiation of ATDC5 cells.
PMID- 9633509
TI - PD 98059 prevents establishment of the spindle assembly checkpoint and inhibits
the G2-M transition in meiotic but not mitotic cell cycles in Xenopus.
AB - Most chemotherapeutic agents block DNA replication, damage DNA, or interfere with
chromosome segregation. The existence of checkpoints, which monitor these events,
indicates that mechanisms exist to avoid death when essential cellular events are
inhibited. A molecular understanding of cellular checkpoints should therefore
provide opportunities for the development of inhibitors of checkpoint controls
which may increase the potency of chemotherapeutic drugs by inducing catastrophic
cell cycle progression. The molecular dissection of cell cycle arrest points is
facilitated in the Xenopus egg/oocyte system, in which cell-free systems retain
both S/M and spindle assembly checkpoints. Members of the MAP kinase family have
been shown to play a role in the induction of G2 to M transition during oocyte
maturation and have been implicated in the maintenance of either cytostatic
factor- or spindle assembly checkpoint-induced M-phase arrest. Here, we have
examined the effects of the inhibitor of MAP kinase kinase activation, PD 98059,
on cell cycle progression in Xenopus oocytes and in cell-free extracts. This
inhibitor is highly specific for the kinase which activates the classical p42/p44
MAP kinase, having no effect on upstream activators of stress-activated protein
kinases. We have found that PD 98059 inhibits oocyte maturation, consistent with
a role for p42 MAP kinase as a rate-limiting component in the induction of
meiosis, but had no effect on the timing of G2-M transition in cell-free extracts
indicating that, unlike meiosis, p42 MAP kinase activation is not limiting for
normal mitotic M phase entry. However, we found that cytostatic factor-induced
metaphase arrest, as well as the spindle assembly checkpoint, were both abolished
in the presence of the drug. These results demonstrate that p42 MAP kinase, and
not some other member of the MAP kinase family, is responsible for both CSF- and
checkpoint-induced metaphase arrest and suggest that PD 98059 and similar agents
may have considerable therapeutic potential for the potentiation of
chemotherapeutic regimes.
PMID- 9633510
TI - Myristoyl-coA:protein N-myristoyltransferase from bovine cardiac muscle:
molecular cloning, kinetic analysis, and in vitro proteolytic cleavage by m
calpain.
AB - Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes the attachment of
myristate onto the amino terminal glycine residue of select polypeptides. Cardiac
tissue expresses high levels of cAMP-dependent protein kinase whose catalytic
subunit is myristoylated; however, cardiac muscle extracts were found to contain
low NMT activities. Northern blot analysis of bovine heart poly(A)+ RNA probed
with bovine spleen NMT cDNA revealed a 1.7-kb mRNA. Western blot analysis of
cardiac muscle extracts with human NMT antibody indicated a prominent
immunoreactive band with a molecular mass of 50 kDa. The expression of mRNA and
protein levels in cardiac muscle is not correlated with NMT activities,
suggesting the presence of regulators of the enzyme activity. We have isolated
the cDNA encoding bovine cardiac muscle NMT (cNMT) by reverse transcription
polymerase chain reaction. The single long open reading frame of 1248 bp of
bovine cNMT specifies a protein of 416 amino acids with a predicted mass of
46,686 Da. The cDNA clone expressed in Escherichia coli resulted in the
production of functionally active 50-kDa NMT. Ultrastructural and
immunolocalization of NMT utilizing the immunogold labeling technique
demonstrated cytoplasmic distribution with occasional mitochondrial and
myofilaments localization of the NMT antibody. Cardiac muscle NMT has a higher
affinity for myristoyl-CoA than toward palmitoyl-CoA. Substrate specificity
indicated that cNMT has a higher affinity toward pp60src and M2 gene segment of
reovirus type 3-derived peptide substrates than toward cAMP-dependent protein
kinase-derived peptide. Primary translational product of cNMT sequence contained
several regions rich in proline, glutamic acid, serine, and threonine, which are
known as "PEST" regions. PEST-FIND analysis of the amino acid sequences indicated
eight PEST regions were present in the cNMT. These PEST regions are suggested to
be recognized by specific proteases, particularly Ca(2+)-dependent neutral
proteases, calpains, which are responsible for the degradation of PEST-containing
proteins. We have demonstrated the abolishment of NMT activity and NMT protein
degradation in vitro by m-calpain. The proteolysis of cNMT by m-calpain and the
abolishment of NMT activity was prevented by the calpain inhibitor, calpastatin.
These observations indicate that calpains may regulate NMT activity.
PMID- 9633511
TI - Entactin-2: a new member of basement membrane protein with high homology to
entactin/nidogen.
AB - Using the new signal sequence trap (SST) method, we isolated several clones
encoding secreted and transmembrane proteins from KUSA cells, a murine osteoblast
like cell line. One isolated novel clone, termed entactin-2, exhibited a high
similarity to mouse entactin/nidogen, a basement membrane protein. Although
deduction of the amino acid sequence of entactin-2 revealed only 27.4% homology
to entactin, many structural similarities were seen between both proteins.
Entactin-2 contains five EGF-like and two thyroglobulin-like motifs, which are
both cysteine-rich. Comparison of both proteins clearly revealed that entactin-2
also contains related domain structures. The rod-like domain of entactin-2,
containing the RGD integrin recognition sequence, fused to glutathione-S
transferase (GST), revealed a cell surface-binding activity similar to that of
entactin. In addition, the tissue distribution of entactin-2 mRNA resembled that
of entactin. Furthermore, mRNA expression of both genes decreased as osteoblastic
differentiation progressed. These results suggest that entactin-2 is a member of
the entactin gene family, may have entactin-related functions, and might act as a
basement membrane component.
PMID- 9633512
TI - Major changes in chromatin condensation suggest the presence of an apoptotic
pathway in plant cells.
AB - A large decrease in fluorescence intensity of propidium iodide (PI)-stained
nuclei is observed during senescence of plant cells. The phenomenon reflects a
decrease in accessibility of DNA to this fluorochrome and is a consequence of
chromatin condensation. This decrease is substantially greater than usually found
in animal nuclei whose chromatin undergoes condensation, e.g., during
differentiation or quiescence. Chromatin condensation was confirmed by analyses
of (i) DNA accessibility to DNase I, (ii) histone disassociation induced by HCl,
(iii) saturation of binding sites by the PI fluorochrome (iv), and (v) visual
inspection by fluorescence and confocal microscopy. The extent of changes
revealed by these assays was used to map progressive changes in chromatin
condensation which allowed us to identify different stages in an apoptosis-like
pathway in plants. The initial step of chromatin condensation which occurred
prior to endonucleolytic DNA degradation was detected by fluorescence and
confocal microscopy and confirmed by a variety of assays employing flow
cytometry. The initial chromatin condensation appears to be a reversible step in
the early stage of apoptosis. The loss of reversibility of chromatin condensation
observed subsequently may be a critical point in the cascade of apoptotic events,
leading to further irreversible changes during apoptosis in plants.
PMID- 9633513
TI - Embryonic stem cells and embryoid bodies express lymphocyte costimulatory
molecules.
AB - Despite the importance of the costimulatory proteins B7-1 (CD80), B7-2 (CD86),
and their counterreceptors CD28 and CTLA-4 (CD154) in the regulation of T cell
proliferation in the adult immunological system, the initial appearance of these
proteins during embryonic development has not been investigated. Using in vitro
cultures of undifferentiated mouse embryonic stem (ES) cells and differentiating
embryoid bodies as a model of very early embryonic development, we examined these
cells for the presence of mRNA and protein corresponding to the B7 and CD28
families of costimulatory molecules. By flow cytometry, a stochastically
regulated subpopulation of B7-1+ cells comprising 33% of total cells was detected
in ES cell cultures, while negligible staining was found for B7-2, CTLA-4, and
CD28. When ES cells were differentiated into embryoid bodies for 12 days, a CD45+
subpopulation of embryoid body cells were found to stain positively for B7-1, B7
2, and CD28. RT-PCR confirmed cell staining data by revealing amplification
products corresponding to B7-1, B7-2, and CD28 in corresponding samples. Very low
levels of CTLA-4 amplification products were found in all samples; however,
surface staining of CTLA-4 was never detected. The functional capacity of ES cell
B7-1 to bind its ligand was verified by the ability of the soluble fusion protein
CTLA-4-Ig to bind ES cells and the ability of this reagent to block anti-B7-1
antibody binding in cell based competition assays. These results demonstrate that
expression of costimulatory molecules arises very early during in vitro
development and suggests that the early embryonic environment may utilize
cellular signaling systems analogous to those seen in the immune system.
PMID- 9633514
TI - S- and G2-phase cell cycle arrests and apoptosis induced by ganciclovir in murine
melanoma cells transduced with herpes simplex virus thymidine kinase.
AB - Mechanism of cell killing by transfer of Herpes simplex virus type-1 thymidine
kinase (HSVtk) and subsequent ganciclovir (GCV) treatment was examined in B16F10
murine melanoma model. While parental B16F10 melanoma cells were resistant to GCV
at 100 microM or higher, HSVtk-transduced B16F10 melanoma cell clones became
susceptible to GCV with IC50 of 0.1 to 0.3 microM. By means of various parameters
including characteristic morphological changes, in situ DNA end-labeling, DNA
ladder pattern, flow cytometric detection of sub-G1 DNA content, and annexin V
binding of inverted cell surface phosphatidylserine, apoptosis was shown to be
associated with the cell killing of ganciclovir on HSVtk-transduced melanoma
B16F10 cells. Kinetic analysis showed that the signs of apoptosis were observed
not until 60 h of continued GCV treatment and preceded first by a rise in p53
protein level in 12 h and then by S-phase/G2-phase cell cycle arrest associated
with corresponding increases in the level of cyclin B1 protein but no apparent
change in protein level of Bax or Cdc2. These results suggest that apoptosis
occurred as a result of ganciclovir-induced cell cycle arrests rather than direct
chemical effect on HSVtk-transduced B16F10 melanoma cells.
PMID- 9633515
TI - The human papillomavirus type 16 E5-protein modulates ligand-dependent activation
of the EGF receptor family in the human epithelial cell line HaCaT.
AB - The E5 open reading frame of the human papillomavirus type 16 encodes a
transmembrane protein associated with the Golgi, ER, and plasma membranes. We
have analyzed the effect of E5 expression on the activation of the EGF receptor
family. We find that expression of the E5-protein strongly enhances EGFR
activation in a ligand-dependent manner. This activation takes place immediately
after addition of ligand, demonstrating that increased tyrosine phosphorylation
cannot solely be due to an impaired downregulation of the receptors. Furthermore,
this activation is not a result of impaired activity of EGFR-specific phosphatase
through the E5-protein, as demonstrated by using inhibitors specifically blocking
EGFR activation. In addition, treatment with EGF results in an enhanced
activation of the ErbB2 receptor in E5-expressing cells. This superactivation
must be a result of heterodimer formation between EGFR and ErbB2, since EGF is
not a ligand for ErbB2. Finally, treatment of E5-expressing cells with HB-EGF
shows no increased phosphorylation of the ErbB4 receptor, suggesting a specific
effect of E5 on the activation of the different members of the EGFR family.
PMID- 9633516
TI - KH domain integrity is required for wild-type localization of Sam68.
AB - The protein Sam68 (Src-associated in mitosis, 68 kDa) has been found to bind to
SH2 and to SH3 domain-containing proteins and to RNA. Although its protein
protein interactions implicate Sam68 in cell signaling, the significance of its
RNA binding remains obscure. In most cells, Sam68 shows diffuse nucleoplasmic
staining. Upon treatment with transcription inhibitors, however, Sam68 localize
into punctate nuclear structures. Mutant forms of mouse Sam68 were overexpressed
in human cells to test the importance of the KH domain, which is required for RNA
binding, in the intracellular localization of Sam68. A small deletion within the
KH domain (delta 206-218) or point mutation I184N had no effect upon the
localization of overexpressed Sam68. Sam68 that contained a deletion of the
entire KH domain (delta KH, delta 157-256) or point mutation G178E, however,
localized to distinct nuclear spots. Furthermore, delta KH Sam68, unlike wild
type Sam68 and several other mutant Sam68 proteins, did not relocalize upon
poliovirus infection and caused the normally cytoplasmic viral polymerase to
localize to the nuclear spots. Thus both ongoing transcription and an intact KH
domain are crucial determinants of the dynamic intracellular localization of
Sam68.
PMID- 9633517
TI - Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity
to paclitaxel by inducing G2/M arrest and apoptosis.
AB - Paclitaxel-induced cytotoxicity, cell cycle perturbation, and apoptosis were
determined in a human ovarian cancer cell line expressing wt p53 (A2780) and in a
subclone (A2780/E6) obtained upon transfection with the product of the E6 gene of
the human papilloma virus HPV16. The inactivation of wt p53 in A2780/E6 was
verified by measuring the inability of the clone to induce p53 and p21 expression
after paclitaxel treatment. The p53-negative clone (A2780/E6) was approximately
50-fold more sensitive to paclitaxel than wt p53-expressing A2780 cells. This
increased sensitivity was related to the ability of paclitaxel to induce a strong
arrest of cells in the G2/M phase of the cell cycle in A2780/E6 but not in A2780
cells. This different cell cycle arrest was accompanied by increased frequency of
paclitaxel-induced p53-independent apoptosis. Initial studies on proteases
activation tend to exclude a direct role of ICE and CPP32 in the induction of
apoptosis in these cells and show a paclitaxel-dependent increase in FLICE
levels, whose biological relevance is however at present not defined.
PMID- 9633518
TI - Oxidative stress leads to a rapid alteration of transferrin receptor
intravesicular trafficking.
AB - Several studies have demonstrated that perturbations of intracellular oxidative
balance play a key role in numerous physiological as well as pathological
conditions leading to various morbidity states. In previous studies we have shown
that the free radical inducer menadione rapidly and specifically downmodulates
the membrane transferrin receptor (TfR) by blocking receptor recycling. This
modulation is due to receptor redistribution and not to receptor loss. Here we
show that other oxidant compounds, such as hydrogen peroxide, also induce a rapid
downmodulation of membrane TfR and that pretreatment of cells with the
antioxidant, thiol supplier, N-acetylcysteine inhibits the downmodulation of
these receptors elicited by either menadione or hydrogen peroxide. This
observation suggests that intracellular thiol redox status may be a critical
determinant of TfR downmodulation induced by oxidative stress. Furthermore,
immunocytochemical results show that, in menadione-treated cells, TfRs are
associated with the Golgi complex, where normally only 20% of total cellular TfRs
is found and is mainly detected in the cytoplasm as scattered punctuations.
Accordingly, menadione and hydrogen peroxide also elicited a downmodulation of
low density lipoprotein receptor (LDLR) which mediates, like TfR, the transport
of nutrients to the cell and is endocytosed through clathrin-coated pits.
Finally, experiments carried out using okadaic acid, an inhibitor of
phosphatases, suggest that H2O2 and menadione downmodulate surface TfR via
different biochemical pathways. Taken together these results suggest the
existence of a potentially important protective mechanism through which iron
uptake is prevented in oxidatively imbalanced cells. Iron uptake can in fact give
rise to the formation of highly toxic hydroxyl radicals reacting with hydrogen
peroxide and leading to cytotoxicity. Downmodulation of surface TfR may thus
represent the physiological control mechanism for reducing iron uptake in diverse
pathological conditions including hypoxia-reperfusion injury, acquired
immunodeficiency syndrome, and aging.
PMID- 9633519
TI - Disruption of the lama2 gene in embryonic stem cells: laminin alpha 2 is
necessary for sustenance of mature muscle cells.
AB - Mutations in the gene coding for the alpha 2 chain of laminin-2 and -4 (merosin)
cause a severe form of congenital muscular dystrophy in humans and mice. To
establish a defined model for in vitro and in vivo studies of the role of laminin
alpha 2/merosin in development and cell and tissue function, we generated several
lines of mutant embryonic stem (ES) cell with disruption of the laminin alpha 2
chain gene. We find that homozygous mutant ES cells differentiate normally in
vitro, giving rise to cardiomyocytes, myotubes, and smooth muscle cells in
addition to many other cell types. However, the myotubes that are formed are
unstable. They detach, collapse, and degenerate, a process which is initiated at
the appearance of the mature, contractile phenotype of the cells. We propose that
the detachment and death of contracting myotubes in vitro has its counterpart in
vivo and that contraction-induced myofiber damage, along with the lack of
survival cues provided by laminin alpha 2/merosin, is a significant contribution
to muscle degeneration in merosin-deficient muscular dystrophy.
PMID- 9633520
TI - FR901228, a potent antitumor antibiotic, is a novel histone deacetylase
inhibitor.
AB - Screening for microbial metabolites that induce transcriptional activation of the
SV40 promoter resulted in the identification of two known compounds, FR901228 and
trichostatin A (TSA). FR901228 is a potent antitumor drug that is currently under
clinical investigation. TSA is a specific inhibitor of histone deacetylase.
Despite structural unrelatedness, both FR901228 and TSA greatly enhanced the
transcriptional activity of the SV40 promoter in an enhancer-dependent manner.
The effects of FR901228 on the cell cycle, chromatin structure, and histone
acetylation were examined and compared with those of TSA. Both compounds caused
arrest of the cell cycle at both G1 and G2/M phases and induction of
internucleosomal breakdown of chromatin. FR901228, like TSA, inhibited
intracellular histone deacetylase activity, as a result of which marked amounts
of acetylated histone species accumulated. FR901228 is therefore a new type of
histone deacetylase inhibitor, whose chemical structure is unrelated to known
inhibitors such as trichostatins and trapoxins.
PMID- 9633521
TI - Antisense wnt-5a mimics wnt-1-mediated C57MG mammary epithelial cell
transformation.
AB - The disruption of the normal expression of wnt-5a in cell lines and in tumors is
becoming increasingly recognized as important in cell transformation and
tumorigenesis. For example, in endometrial cancer wnt-5a is downregulated
compared to normal tissue. Our laboratory has recently found that the ectopic
expression of wnt-5a in human RCC23 renal carcinoma cells missing wnt-5a gene
expression suppresses in vitro cell growth and telomerase enzyme activity.
Furthermore, ectopic wnt-5a in MC-T16 uroepithelial cancer cells missing the
region of chromosome 3p where wnt-5a has been mapped reverts uroepithelial cell
tumorigenesis in athymic nude mice. These studies were based upon the previous
finding that wnt-1 and wnt-2 transform C57MG mammary epithelial cells by
downregulating the endogenous expression of wnt-5a. We now report that
transfecting C57MG cells with a mammalian expression vector carrying antisense
wnt-5a results in a cell phenotype that mimics cell transformation by ectopic wnt
1 or wnt-2. Correspondingly, wnt-1-transformed cells are partially reverted in
the presence of ectopic wnt-5a. We conclude from this that wnt-5a is an important
regulator of cell growth and differentiation and its loss of expression leads to
cell transformation.
PMID- 9633522
TI - Effect of type II collagen in chondrocyte response to TGF-beta 1 regulation.
AB - The in vivo role of the extracellular matrix and the manner in which it
interfaces with soluble regulators remains unknown. This study reports the
modulation by extracellular type II collagen of TGF-beta 1-stimulated DNA
synthesis, proteoglycan synthesis, and mRNA expression for alpha 1(II)
procollagen and aggrecan core protein in the adult articular chondrocyte. Bovine
chondrocytes were isolated and resuspended in alginate beads which contained
increasing amounts of type II collagen from 0 to 1.5% (w/v). Cultures were
maintained for 7 days in basal, DMEM, TGF-beta 1 (10 ng/ml), or FBS (10%)
supplemented medium. DNA and proteoglycan synthesis were determined by
radiotracer incorporation. The relative amounts of mRNA were analyzed by Northern
blot analysis. Exogenous collagen increased DNA synthesis in all culture
conditions beginning at concentrations of 0.75% (w/v). We observed that
extracellular type II collagen augments both TGF-beta 1 stimulated increases of
aggrecan gene expression up to 400% and alpha 1(II) procollagen gene expression
up to 180% in a dose-dependent fashion. This is distinct from cultures which were
either basal or FBS supplemented medium which lacked a dose-dependent change in
aggrecan gene expression and demonstrated a decrease in alpha 1(II) procollagen
gene expression. Exogenous collagen above 0.75% (w/v) increased proteoglycan
synthesis significantly in FBS and TGF-beta 1-stimulated cultures but not in
basal cultures. We have demonstrated that the alterations in gene expression that
occur in response to TGF-beta 1 are modulated by extracellular type II collagen.
This modulation is possible through both transcriptional and posttranscriptional
regulatory mechanisms.
PMID- 9633523
TI - The conventional transforming growth factor-beta (TGF-beta) receptor type I is
not required for TGF-beta 1 signaling in a human prostate cancer cell line,
LNCaP.
AB - LNCaP is an androgen-responsive human prostate cancer cell line that has a
defective gene for ALK-5, the conventional TGF-beta receptor type I. Yet, these
cells respond to exogenous TGF-beta 1 under appropriate concentrations of
dihydrotestosterone (DHT). Because a heteromeric complex composed of type I and
type II receptor is required for TGF-beta signaling, the expression of these
receptors was investigated in LNCaP cells at following concentrations of DHT-0,
0.1, and 100 nM. These concentrations were selected because they represent the
zero DHT control in which LNCaP cells are not sensitive to TGF-beta 1, the
proliferative dose of DHT in which these cells are sensitive to exogenous TGF
beta 1, and the growth-arrest dose of DHT in which LNCaP exhibits signs of TGF
beta signaling but are insensitive to exogenous TGF-beta 1, respectively. Results
of Western blot analysis showed that LNCaP cells express an increased level of
type II receptor at 0.1 nM DHT, the TGF-beta 1-sensitive dose. However, results
of competitive quantitative RT-PCR demonstrated that DHT did not significantly
change the level of type II receptor mRNA, suggesting that DHT modulates the
level of type II receptor at the posttranscriptional level. In contrast, ALK-5
was not detected in these cells by either Western blot analysis or RT-PCR at all
concentrations of DHT used in this study. Subsequently, the expression of ALK-1,
2, and -4 in LNCaP cells was examined because these proteins have been shown to
bind TGF-beta 1 in vitro. ALK-1 and -2 were detected in these cells. Further
analysis by competitive quantitative RT-PCR and Western blot demonstrated that
DHT did not affect the level of expression of ALK-1 and -2 in LNCaP cells. These
observations, taken together, demonstrate that ALK-5 is not required for TGF-beta
1 signaling and that there may be alternative mechanism(s) for TGF-beta 1 signal
transduction in some systems.
PMID- 9633524
TI - Differential binding characteristics and cellular inhibition by soluble VEGF
receptors 1 and 2.
AB - The FLT-1 and KDR genes encode transmembrane tyrosine kinases which function as
high-affinity receptors for vascular endothelial growth factor (VEGF). We have
used the baculovirus system to express the extracellular parts of the FLT-1
receptor and KDR receptor in soluble form (sFLT-1 and sKDR), for in vitro binding
and competition assays. Here, we show that the binding of VEGF165 to sKDR but not
sFLT-1 is dependent on heparin, regardless of whether VEGF165 or sKDR is
immobilized. Further, only sFLT-1 acts as a receptor antagonist in solution and
sKDR can neither compete with the binding of VEGF165 to human endothelial cells
carrying both receptors nor block VEGF165 induced mitogenicity. Soluble KDR only
partially inhibits cell migration even at high concentrations, in contrast to
sFLT which can almost completely block (82%) VEGF-induced cell proliferation and
migration. Taken together these results show that the two soluble VEGF receptor
proteins, sFLT-1 and sKDR, despite binding the same ligand, behave very
differently when immobilized with regard to their dependence on heparin for VEGF
binding. In solution their respective ability to function as receptor antagonists
is also strikingly different, possibly a reflection of their different dependency
on heparin.
PMID- 9633525
TI - HB-GAM/pleiotrophin but not RIHB/midkine enhances chondrogenesis in micromass
culture.
AB - The heparin-binding growth-associated molecule HB-GAM (also named pleiotrophin)
and the retinoic acid-induced heparin-binding protein RIHB (chicken midkine) are
developmentally regulated proteins forming a new family of heparin-binding
molecules with putative functions during cell growth and differentiation. A
direct involvement of these molecules during chondrogenesis in vivo was suggested
by their patterns of expression. The putative chondrogenic activity of these
molecules was investigated in vitro using micromass cultures from chicken limb
bud mesenchymal cells. Exogenous HB-GAM, not RIHB, was found to enhance
chondrogenesis in this system. These results provide a strong incentive for
considering and further investigating the role of this protein in the control of
limb cartilage differentiation.
PMID- 9633526
TI - The role of the hydrophobic domain in orienting natural signal sequences within
the ER membrane.
AB - The orientation of signal sequences during insertion into the endoplasmic
reticulum membrane is largely determined by the charged residues flanking the
apolar domain. Using recombinant and mutant proteins, also length and
hydrophobicity of the apolar segment were shown to affect the orientation:
translocation of the N-terminus was found to be favored by long hydrophobic
sequences, and translocation of the C-terminus, by short ones. Here, we tested
the physiological significance of this phenomenon by mutagenesis of the
hydrophobic portion of two natural signals with unusual flanking charges.
Extending the hydrophobic domain of the short, cleaved Ncyt/Cexo signal of pre
provasopressin-neurophysin II and shortening that of the Nexo/Ccyt signal anchor
of microsomal epoxide hydrolase resulted in a significant fraction of
polypeptides inserting in the opposite orientation to that of the wild-type
proteins. The topogenic contribution of the hydrophobic domain is thus important
for the correct and uniform orientation of natural proteins and can explain the
behavior of some of the signals with unusual flanking charges.
PMID- 9633527
TI - Mechanisms of increased NGF production in vascular smooth muscle of the
spontaneously hypertensive rat.
AB - The spontaneously hypertensive rat (SHR) was developed as a genetic model of
essential hypertension. In vivo and in vitro evidence demonstrates that vascular
smooth muscle cells (VSMCs) from the SHR produce more nerve growth factor (NGF)
than the normotensive Wistar-Kyoto (WKY) control strain. This increased NGF
production is accompanied by excessive innervation of target tissues in the SHR.
In the present study, a sensitive, competitive, quantitative, reverse
transcriptase polymerase chain reaction (C Q RT-PCR) assay is characterized and
used to analyze levels of NGF mRNA in cultured VSMCs derived from the SHR and WKY
strains as well as bladder tissue. Differences in NGF secretion rates between SHR
and WKY VSMCs were partially due to an increased stability of NGF mRNA in SHR
VSMCs. Following treatment with platelet-derived growth factor (PDGF) and
transforming growth factor-beta (TGF-beta 1) to elevate NGF production, the half
life of the NGF mRNA was 104.5 +/- 18.0 min in SHR VSMCs, compared to only 36.5
+/- 11.6 min in WKY VSMCs. Sequence analysis of the 3' untranslated region (UTR)
revealed no strain differences in cis-acting sequences potentially involved in
determining mRNA stability. Thus, it seems unlikely to be a 3'UTR mutation that
prolongs mRNA lifetime. Rather, differential regulation of an RNA-binding protein
may play a role in the abnormal NGF mRNA stability in SHR VSMCs. SHR VSMCs also
demonstrate an increased translational efficiency of NGF protein; more NGF
protein is synthesized per unit of NGF mRNA. The use of a C Q RT-PCR assay has
allowed the determination that abnormal NGF mRNA stabilization as well as altered
translational efficiency may contribute to excess NGF synthesis and progressive
hypertension in the SHR.
PMID- 9633528
TI - Differentiation-related pathways of 1 alpha,25-dihydroxycholecalciferol
metabolism in human colon adenocarcinoma-derived Caco-2 cells: production of 1
alpha,25-dihydroxy-3epi-cholecalciferol.
AB - We used the human colon adenocarcinoma-derived cell line Caco-2, which
spontaneously differentiates in vitro, as a model system to investigate the
metabolism of 1 alpha,25-dihydroxycholecalciferol in colon cancer cells.
Subconfluent proliferating and confluent differentiating cells were incubated
with 1 microM 1 alpha,25-dihydroxycholecalciferol for a period of 24 to 48 h.
HPLC analysis of the lipid extract of both cells and media was performed to
isolate and identify the various metabolites of 1 alpha,25
dihydroxycholecalciferol. Undifferentiated, highly proliferating Caco-2 cells
metabolized 1 alpha, 25-dihydroxycholecalciferol into several side chain modified
metabolites formed through the C-24 oxidation pathway. In contrast, no
metabolites of the C-24 oxidation pathway were identified in differentiated Caco
2 cells. However, differentiated cells produced significant amounts of a
metabolite which was less polar than 1 alpha, 25-dihydroxycholecalciferol on a
straight phase HPLC system. This metabolite was identified as 1 alpha,25
dihydroxy-3alpha-cholecalciferol by comigration with a synthetic standard on two
different HPLC systems and gas chromatography--mass spectrometry. Thus, we were
able to demonstrate that the state of differentiation has a profound influence on
1 alpha,25-dihydroxycholecalciferol metabolism in colon cancer cells.
PMID- 9633529
TI - Repositioning of human interphase chromosomes by nucleolar dynamics in the
reverse transformation of HT1080 fibrosarcoma cells.
AB - An experimental system which should be valuable for studying the role of spatial
positioning of the nuclear genome in human cell function has been developed.
Reverse transformation of the malignant HT1080 fibrosarcoma cell line upon
treatment with 8-chloro-cAMP results in growth inhibition, cytoskeletal
reorganization, changes in nuclear shape and chromatin accessibility, and
formation of prominent nucleoli. Fluorescent in situ hybridization was used to
study DNA positioning during nuclear remodeling. Morphometric analysis of the
hybridization sites for both repetitive sequences and "painting probes" for whole
chromosomes indicated dispersal of acrocentric chromosomes in untreated cells and
a highly organized central location of these ribosome gene-containing chromosomes
in association with one or a few large nucleoli in nondividing treated cells. The
results suggest that there was a directed movement of interphase chromosomes
during a response which normalized a malignant cell line. These large-scale
repositionings may serve two functions in restoring a normal transcriptional
setup to the nucleus. First, ribosome genes are placed in the nucleolus, their
transcriptional suborganelle. Second, nucleolar anchorings together with
additional perinucleolar centromeric associations orient the domain shapes of
entire chromosomes, installing gene-rich chromosomal regions into pockets of
(accessible) DNAse I-sensitive chromatin populated by spliceosomes.
PMID- 9633530
TI - Suppression of fibroblast growth factors 1 and 2 by antisense oligonucleotides in
embryonic chick retinal cells in vitro inhibits neuronal differentiation and
survival.
AB - As retinal histogenesis proceeds there is a pronounced increase in the expression
of fibroblast growth factor (FGF), reaching its maximum in the mature retina and
largely in terminal differentiated retinal neurons. Recent in vivo evidence
suggests that exogenous FGF functions as a differentiation and survival factor
for a wide variety of cell types including CNS neurons and that endogenous FGF
may perform similar functions. We have examined the consequences of selectively
and independently inhibiting FGF1 or FGF2 expression using antisense
oligonucleotides in embryonic chick retinal cells, differentiating in vitro.
Whether FGF1 or FGF2 expression was inhibited the results were the same: a marked
reduction in neuronal photoreceptor cells differentiation, an increase in
programmed cell death, but no effects on cell proliferation. Even although these
two related factors promote the same final effect on retinal cells, namely,
neuronal differentiation and survival, their normal combined activities or levels
appear to be important in achieving this effect. Stimulation with either
exogenous FGF1 or FGF2 served to increase endogenous levels of both FGF1 and FGF2
and reversed the effects of antisense blockade of either FGF1 or FGF2. Our data
suggest that although other sources of FGF exist within the eye, the function of
endogenous FGF in differentiating retinal neurons may be to stimulate their
differentiation and promote their survival.
PMID- 9633531
TI - Differential regulation of cyclooxygenases 1 and 2 by interleukin-1 beta, tumor
necrosis factor-alpha, and transforming growth factor-beta 1 in human lung
fibroblasts.
AB - In the present studies we found that incubation of human lung fibroblasts with
transforming growth factor-beta 1 (TGF-beta 1) potentiated the interleukin-1 beta
(IL-1 beta) and/or tumor necrosis factor-alpha (TNF-alpha)-stimulated production
of prostaglandin E2 (PGE2). Analysis of fibroblast proteins showed the induction
of cyclooxygenase-1 (Cox-1) by TGF-beta 1 and the induction of Cox-2 by IL-1 beta
and TNF-alpha. The levels of transcripts for Cox-1 were minimally modified by IL
1 beta or TNF-alpha, however, they were increased by 12-fold by TGF-beta 1.
Transcripts for Cox-2 were induced by IL-1 beta or TNF-alpha and their induction
was potentiated by TGF-beta 1. TGF-beta 1 alone did not induce Cox-2 transcripts.
In vitro transcription assays showed that IL-1 beta and TNF-alpha increased the
transcription of the Cox-2 gene, whereas TGF-beta 1 had no effect. Addition of
TGF-beta did not increase further the transcription of Cox-2 in IL-1 beta-treated
cells, but increased the stability of the corresponding transcripts. The
transcription rate of the Cox-1 gene was not increased by any of the cytokines
studied. In summary, we demonstrate that the potentiation of PGE2 production by
TGF-beta 1 in IL-1 beta and TNF-alpha-treated fibroblasts is the result of
transcriptional stimulation of the Cox-2 gene by IL-1 beta and TNF-alpha and the
stabilization of the resulting transcripts by TGF-beta 1.
PMID- 9633532
TI - Type VI collagen increases cell survival and prevents anti-beta 1 integrin
mediated apoptosis.
AB - Cell-matrix interactions are important in the development of the avian cornea.
Type VI collagen is present within the periocular mesenchyme prior to the
migration of cells into the corneal stroma and is abundant in the mature stroma.
Whether the interaction of cells with type VI collagen is essential for cellular
survival in the cornea is not known. In the present study, we examined the
interaction of corneal cells with type VI collagen in vitro to determine if it
can increase cell proliferation and decrease apoptosis. In vivo analysis
demonstrated that apoptosis occurs in the periocular region during early stages
of avian corneal development, but in fully mature corneas apoptosis only occurs
in the corneal epithelium and not in the stroma. In vitro analysis examined the
importance of beta 1 integrin interactions with type VI collagen in mature
corneal fibroblasts and the precursor cells. Using an anti-beta 1 integrin
blocking antibody, CSAT, integrin/matrix interactions were disrupted. Results
indicated that viability of both corneal fibroblasts and periocular mesenchyme
cells was greater on type VI collagen than on type I collagen or BSA-blocked
glass. In addition, less apoptosis was observed for both cell types on type VI
collagen when beta 1 integrin--matrix interactions were disrupted. These data
indicated that these cells require intact beta 1 interactions with type I
collagen and with BSA-coated glass controls to remain viable. Thus, type VI
collagen may play a role in the rescue of corneal cells from anti-beta 1 integrin
induced apoptosis by increasing cell survival, probably via a non-beta 1 integrin
dependent mechanism.
PMID- 9633533
TI - Cytoplasmic localization of LIM-kinase 1 is directed by a short sequence within
the PDZ domain.
AB - LIM-containing protein kinase 1 (LIMK1) is a serine/threonine kinase with a
structure composed of two LIM domains, a PDZ domain, and a protein kinase domain.
We examined the subcellular localization of LIMK1 and its variously deleted
mutants in HeLa cells by transfection with these cDNAs. Immunofluorescence
analysis revealed that the full-length LIMK1 and its mutants deleted with LIM
domain or protein kinase domain preferentially localized in the cytoplasm, while
the mutants deleted with the PDZ domain or a 52 amino acid region (B region)
within the PDZ domain localized mainly in the nucleus. When the normally nuclear
cyclin A was fused with the PDZ domain or the B region of LIMK1, it was localized
in the cytoplasm of transfected cells. The corresponding region of the PDZ domain
of postsynaptic density protein (PSD)-95 had no such function. Additionally, the
PDZ domain of LIMK1 had no potential to bind to the C-terminal S/TXV peptides, to
which the PSD-95 PDZ domain can bind. Taken together these results suggest that
the PDZ domain, particularly the B region, of LIMK1 has a specific function to
localize the protein in the cytoplasm. When glutathione S-transferase (GST) fused
with the PDZ domain of LIMK1 (GST-PDZ) or GST-PDZ deleted with the B region (GST
PDZ delta B) was microinjected into the nucleus of COS cells, GST-PDZ was almost
completely excluded from the nucleus within 30 min, whereas GST-PDZ delta B
remained in the nucleus. These findings suggest that the B region of LIMK1
probably has nuclear export signal activity.
PMID- 9633534
TI - Structure-function relationships of pheromones of the ciliate Euplotes raikovi
with mammalian growth factors: cross-reactivity between Er-1 and interleukin-2
systems.
AB - Diffusible protein signals of the ciliate Euplotes raikovi, denoted as
pheromones, have functionally been linked with prototypic growth factors of
animal cells by the demonstration that they not only induce a temporary cell
union in mating pairs, by acting in a paracrine-like fashion, but can also bind
to cells in autocrine fashion and promote their vegetative (mitotic)
proliferation. It is now shown that pheromone Er-1 is capable of binding to the
alpha and beta chains of the multimeric IL-2 receptor on mammalian cells and that
IL-2 can, in turn, bind to the putative cell receptor of this pheromone.
Similarities in the IL-2 and Er-1 structures support these findings and raise
controversial implications with regard to their evolutionary significance.
PMID- 9633535
TI - Stability of the replicative Mcm3 protein in proliferating and differentiating
human cells.
AB - Mcm proteins are abundant nuclear proteins involved in the regulation of genome
replication. Previous experiments had shown that levels of Mcm-specific mRNAs
increase at the G1/S phase transition of the cell cycle, but that the amounts of
Mcm proteins do not change much during the cell cycle. To learn more about the
stability of an Mcm protein we performed experiments which showed that: (i) more
than 60% of [35S]methionine pulse-labeled Mcm3 protein appears to be degraded
during a 24-h chase in HeLa cells; (ii) the amount of Mcm3 protein significantly
decreases during the differentiation of HL60 cells in vitro (whereas another
replication-initiation protein, hOrc2, remains fairly constant); and (iii)
according to immunohistochemical staining, Mcm3 protein is present in nuclei of
cells in the proliferating zone of human epidermal tissue, but in decreasing
amounts in nuclei of differentiating cells of the upper cell layers. Our
interpretation is that Mcm3 protein is no longer synthesized after initiation of
differentiation and slowly disappears at a half-life of approximately 24 h.
PMID- 9633536
TI - Sex steroids do not prevent amylin-induced apoptosis in human cells.
AB - Formation of amylin-containing islet amyloid deposits may contribute to the
progressive deterioration of beta cell function in non-insulin-dependent diabetes
mellitus. As diabetes mellitus occurs in male, but rarely in female transgenic
mice expressing human amylin in their pancreatic beta cells, it is of interest to
study the influence of estradiol (E2) and testosterone (T) on amylin-induced
cytotoxicity in human cells. The insulinoma cell line CM, thyroid epithelial
cells (TEC) in primary culture, and nontransformed fibroblast lines were used.
The occurrence of apoptotic cell death was assessed by nuclear labeling with
propidium iodide. Amylin was cytotoxic on all cell types tested, but had the most
pronounced effect on TEC and the weakest on the CM cell line. Although both E2
and T decreased the proportion of apoptotic cells in cultures kept in the absence
of amylin, neither of the two hormones was able to counteract amylin-induced
cytotoxicity. beta cell death and hyperglycemia can thus presumably not be
prevented by the neutralization of amylin effects by sex steroids.
PMID- 9633537
TI - Estrogen treatment induces elevated expression of HMG1 in MCF-7 cells.
AB - The high mobility group (HMG) 1 protein is a highly conserved and ubiquitous
chromosomal protein found enriched in active chromatin. In this study, we have
investigated the effect of estrogen on the expression of the human high mobility
group protein HMG1 gene and found that the HMG1 mRNA level in MCF-7 cells was
sharply increased 2.5-fold after 30 min of estrogen treatment. Under continuous
estrogen treatment, the HMG1 mRNA level decreased to a 1.5 times that of the
basal level at 90 min and remained at this elevated level under estrogen
treatment for up to 24 h. These results support the recent finding by Verrier et
al. (C.S. Verrier, 1997, Mol. Endocrinol. 11, 1009-1019) that HMG1 promotes the
binding of the estrogen receptor to the estrogen response element and further
reinforce our believe that HMG1 plays a significant role in estrogen-induced gene
expression.
PMID- 9633538
TI - Preventing the preventable. Undervalued and underfunded screening is undermining
primary care.
PMID- 9633539
TI - Cultural changes in healthcare.
PMID- 9633540
TI - Cultural changes in healthcare.
PMID- 9633541
TI - The elusive diagnosis of appendicitis.
PMID- 9633542
TI - Update on upper gastrointestinal bleeding. Basing treatment decisions on
patients' risk level.
AB - Acute upper gastrointestinal bleeding is a common reason for hospitalization.
Mortality rates range from 5% to 15%; patients with severe comorbidities and
those with persistent or recurrent bleeding are at highest risk. Accurate
preliminary risk assessment and resuscitation can proceed simultaneously at
initial presentation. Risk assessment can guide treatment decisions. Early upper
gastrointestinal endoscopy, a cornerstone of management, allows for rapid
diagnosis, application of endoscopic therapy, and completion of risk assessment.
Endoscopic therapy can alter the natural history of upper gastrointestinal
bleeding by reducing rates of further bleeding and, consequently, mortality.
Complete risk assessment of both clinical and endoscopic factors can likely
result in shorter hospital stays and improved outcomes. Early assessment helps
identify low-risk patients in whom discharge on the day of presentation is
appropriate.
PMID- 9633543
TI - Newer oral antimicrobials for resistant respiratory tract pathogens. Which show
the most promise?
AB - As antimicrobial resistance to tried-and-true drugs continues to build, an
arsenal of new drugs aimed at resistant respiratory tract pathogens is needed.
Penicillin is now ineffective against several common pathogens, including many
pneumococcal organisms. Newer antimicrobials, including macrolides,
cephalosporins, and fluoroquinolones, have been developed to take its place. The
authors of this article present a progress report of the fight against
respiratory tract infection and an assessment of the most promising newer agents
for use against multidrug-resistant pathogens.
PMID- 9633544
TI - Bites and stings of the arthropod kind. Treating reactions that can range from
annoying to menacing.
AB - Bites and stings from arthropods are largely inevitable because of the number of
offending species and their distribution throughout our environment. Wasps, bees,
ants, mosquitoes, gnats, chiggers, and fleas are found all across the United
States. Thus far, Africanized honeybees are limited to southwestern states and
fire ants to southern states. Brown recluse spiders are found most often in the
Midwest and south central region, but the black widow spider is found in all 48
contiguous states. The dangerous Centruroides species of scorpion live mostly in
southern states and California. Fortunately, in most people, bites and stings
from arthropods produce only self-limited reactions, which can usually be managed
with cold packs, analgesics, and topical agents. In the few encounters that
produce serious reactions, prompt diagnosis and appropriate treatment result in a
good outcome in nearly all cases. The number of stings and bites can be reduced
with use of a few basic avoidance and protection measures.
PMID- 9633545
TI - Heat-related illness. Plan ahead to protect your patients.
AB - Environmental heat illnesses range from irksome to devastating. People at
particular risk are the elderly, the chronically mentally ill, the community
dwelling developmentally delayed, people without social contacts, athletes, and
those without access to air-conditioning. Because heat-related deaths are
preventable, community-wide response to heat emergencies, together with
individual and community education programs, could greatly decrease morbidity and
mortality.
PMID- 9633546
TI - Food poisoning. Causes, remedies, and prevention.
AB - Food producers and consumers must continue to take precautions against foodborne
diseases, and early diagnosis and appropriate treatment of these illnesses are
essential. Food products and water can become contaminated with microorganisms
and toxins that make people ill, and the very young, the elderly, and
immunocompromised individuals are especially susceptible. Education of healthcare
providers, food handlers, and the public is critical in reducing the incidence
and spread of foodborne illness. Changes in eating habits and lifestyle and
increased availability of both domestic and imported foods have made food hazards
a more complex public health issue. Although most foodborne illnesses can be
avoided by safe food handling procedures (see box on page 134), risk reduction is
very important at every step from source to table. A concerted effort is needed
to ensure continuing safety of the food supply in the United States while also
assuring access to a wide variety of healthful foods. Time will tell whether
consumers will accept irradiation of meats. If accepted, irradiation could rank
in importance with pasteurization of milk and chlorination of water as a public
health measure.
PMID- 9633547
TI - Near drowning. Rescuing patients through education as well as treatment.
AB - Optimal prehospital care of near-drowning victims requires bystanders and
emergency-response personnel who are knowledgeable in CPR and proper rescue
techniques. Primary care physicians can play an important role when asked to
teach CPR, first-responder, or emergency-care classes or to serve as medical
director for a local ambulance group. Rapid response and appropriate ventilation
and airway protection by prehospitalization providers can improve the condition
of near-drowning victims on arrival in the emergency department and their chances
for neurologically intact survival. With knowledge of the local risks of
drowning, proper emergency treatment, appropriate referral, and conscientious
efforts at prevention conducted in the office and the community, primary care
physicians can have maximum impact on this summer-time killer.
PMID- 9633548
TI - Acute sinusitis in adults. The Institute for Clinical Systems Integration.
PMID- 9633549
TI - Valvular and coronary heart disease. When is it time for surgical referral?
AB - Decisions about when to refer patients for cardiac surgery remain dynamic in the
face of rapidly advancing technology. Coexisting health problems obviously play
an important role, as do the natural history of the cardiovascular disorder, the
indications for surgery, and the risks associated with the operative procedure.
Nonetheless, many patients can be offered the possibility of improved
cardiovascular function and survival through cardiac interventions.
PMID- 9633550
TI - Evaluating facial paralysis. Expensive diagnostic tests are often unnecessary.
AB - In most cases, the cause of facial paralysis can be determined on the basis of
the clinical evaluation, and expensive diagnostic tests can be avoided. Because
Bell's palsy is not always the cause, physicians need to be able to identify
critical findings on history and physical examination that indicate an
alternative diagnosis. Once identified, these findings can lead to a specific and
directed evaluation.
PMID- 9633551
TI - The case of the confusing cardiogram. Multifocal atrial tachycardia.
PMID- 9633552
TI - Thrombotic thrombocytopenic purpura that is refractory to therapeutic plasma
exchange in two patients with occult infection.
AB - BACKGROUND: The etiology of thrombotic thrombocytopenic purpura (TTP) remains
undetermined. TTP has been associated with a number of secondary causes including
infections, drugs, menses, pregnancy, autoimmune diseases, and bone marrow
transplantation. Regardless of the inciting factors, it is widely accepted that
endothelial injury and platelet aggregation are integral components. The
morbidity and mortality have been significantly reduced with the use of
plasmapheresis. However, refractory forms of TTP remain a clinical management
challenge. Refractory TTP has not previously been associated with occult
bacterial infection. CASE REPORT: Two patients had classic TTP that was
refractory to daily plasma exchange with fresh-frozen plasma. Multiple attempts
over a period of months to wean these patients off plasma exchange resulted in
exacerbations of disease activity, as indicated by increased schistocytosis,
decreased hematocrit, increased serum lactate dehydrogenase, and decreased
platelet counts. Both patients were empirically treated for infections during
hospitalization, although microbial cultures failed to isolate an organism.
Discontinuation of antimicrobial therapy on multiple occasions in one patient was
associated with recurrence of disease. In the other patient, dental extraction
with drainage of an occult periodontal abscess resulted in sustained remission of
disease. CONCLUSION: Occult bacterial infection may play a role in triggering and
sustaining TTP that is refractory to conventional treatment. A careful search for
such an infection and appropriate antimicrobial therapy should be considered in
the management of these patients.
PMID- 9633553
TI - Effect of 24-hour storage at 25 degrees C on the in vitro storage characteristics
of CPDA-1 packed red cells.
AB - BACKGROUND: Packed red cells (RBCs) warmed above 10 degrees C are generally
discarded. Few data exist on the degree of accelerated metabolism and increased
hemolysis of packed RBCs allowed to warm. STUDY DESIGN AND METHODS: Twenty-four
CPDA-1 packed RBC units were combined in 3-unit pools and subdivided into 2 test
units and a control unit. One test unit from each pool was warmed to 25 degrees C
for 24 hours on Day 6 and the other test unit was warmed on Day 20; control units
were maintained at 1 to 6 degrees C. RBC and supernatant chemistries and RBC
morphology were measured weekly (Days 0, 7, 14, 21, and 28) and on the day before
warming (Days 6 and 20). RESULTS: Warming CPDA-1 packed RBCs accelerated the
catabolism of glucose 10-fold and produced concentrations of glucose, lactate,
and ATP after 25 days of storage that were equivalent to those in unwarmed units
at 35 days. Supernatant sodium and potassium concentrations were corrected
partially with warming. RBC morphology transiently normalized with warming and
without increased hemolysis; no bacteria growth was detected. CONCLUSION: One day
of 25 degrees C storage of CPDA-1 packed RBCs accelerates essential metabolite
break-down equivalent to 10 days of storage at 1 to 6 degrees C. It does not
appear to matter whether the packed RBCs are warmed on Day 6 or Day 20. This
information may be useful in determining the acceptability of blood allowed to
warm above 10 degrees C.
PMID- 9633554
TI - Quality control of white cell-reduced red cells: white cell preservation and
simplified counting.
AB - BACKGROUND: White cell (WBC) degradation restricts the interval between the
filtration process and the assay for residual WBCs. Maintaining WBC integrity
would permit extended sample storage for batching and/or shipment to centralized
laboratories. The usual quality control assay for WBC-reduced red cell units
requires determining the number of WBCs in the entire counting area of a Nageotte
hemocytometer, which consists of 40 rows. Reducing the counting area would
simplify the quality control procedure. STUDY DESIGN AND METHODS: Adsol red cell
units were prepared either on the day of collection (Day 0) or on Day 1 and WBC
reduced by filtration on the same day. By using prefiltration and postfiltration
red cells, samples containing WBC concentrations of 15, 10, and 3 WBCs per microL
were prepared by serial dilution. Identical samples were treated with
glutaraldehyde and stored at either 20 to 24 degrees C or 1 to 6 degrees C. All
samples were assayed on the day of component preparation and on Days 7 and 14.
The numbers of WBCs corresponding to 10- and 40-row areas of the Nageotte
hemocytometer were determined. RESULTS: For the conditions and WBC concentration
range studied, no significant changes in WBC concentrations were observed through
Day 14 for glutaraldehyde-treated samples stored at either temperature, although
there were substantial decreases in untreated samples. A 10-row measurement was
determined to be sufficient for identifying WBC-reduced red cell units passing
the present limit of 5 x 10(6) residual WBCs. CONCLUSION: Glutaraldehyde
treatment can preserve WBCs in red cell samples at least up to Day 14, which
provides increased efficiency in quality control for laboratories. Current red
cell WBC-reduction filters produce components that, when assayed, contain fewer
than 10 WBCs per full counting area. The simplified procedure would allow
reduction of the counting area by 75 percent.
PMID- 9633555
TI - RHD genotyping in weak D phenotypes by multiple polymerase chain reactions.
AB - BACKGROUND: Weak D phenotypes involve a quantitative variation of D. The genomic
basis in weak D has been disputed, however. STUDY DESIGN AND METHODS: Five
sequence-specific polymerase chain reactions (SSP-PCRs) on exons 2, 5, and 7 of
the RHD gene were evaluated in 248 white and 98 Japanese blood donors and
compared with the results obtained by amplification of intron 4 and serology. All
methods and SSP-PCR testing on the 3' non-coding region of the RHD gene were
applied to the genotyping of 94 DNA samples derived from individuals expressing
weak D phenotypes. RESULTS: Concordant results were obtained with all genotyping
and phenotyping methods in testing 201 D-positive and 145 D-negative donors. Four
of 94 weak D samples were typed as D-negative by amplification of intron 4 and
SSP-PCR on exon 5. Phenotyping with monoclonal antibodies revealed a DVI category
in one of these cases and DFR phenotype in three of these cases. One weak D
sample, which reacted like normal D-positive cells with all applied monoclonal
antibodies, was typed falsely negative by SSP-PCR on exon 5 because of a point
mutation at nucleotide 667 (T-->G) that resulted in a Phe223Val amino acid
substitution. In this individual, heterozygosity was found at two other amino
acid positions (Glu233Gln and Val238Met) by restriction fragment length
polymorphism analysis. CONCLUSION: Genetic diversity in weak D phenotypes is
rare. Only 1 of 90 true weak D phenotypes (1.1%) had a genetic variation in
testing on seven gene regions of the RHD gene.
PMID- 9633556
TI - An Israeli family with six cisAB members: serologic and enzymatic studies.
AB - BACKGROUND: The cisAB blood type is a rare phenomenon in which both the A and B
blood types are inherited from a single parent. Several forms of this phenotype
have been characterized that differ with respect to serologic reactions and the
activities of the gene-encoded blood group A and B transferases. STUDY DESIGN AND
METHODS: The cisAB blood type was suspected when a baby typed as blood group O
was born to a mother whose blood group was AB. Family studies revealed four
generations in whom the pattern of inheritance could be explained only by the
inheritance of the cisAB genotype. Blood and saliva samples from the family were
tested serologically and assayed for the relevant glycosyltransferases. Samples
suitable for DNA analysis were not available. RESULTS: Six family members were
shown serologically to be of the cisAB type. The A and B transferases in the sera
of these individuals were 20 to 35 and 25 to 50 percent of those obtained for A
and B individuals, respectively. The enzymic characteristics of the A and B
transferases were determined. The A transferase in the sera of the cisAB persons
did not bind to agarose beads. CONCLUSION: The family described carries the cisAB
gene, which encodes production of A and B transferases that differ from those of
"normal" A, AB, and B controls. This variant has properties that are distinctly
different from those described in other reports.
PMID- 9633557
TI - Increase in endogenous thrombopoietin in healthy donors after automated
plateletpheresis.
AB - BACKGROUND: Thrombopoietin (TPO) is a key cytokine involved in the regulation of
megakaryocytopoiesis and platelet production. The aim of the present study was to
test whether platelet donation is associated with changes in the serum TPO levels
in healthy donors undergoing plateletpheresis. STUDY DESIGN AND METHODS: The
study group consisted of 23 healthy donors undergoing single-donor
plateletpheresis for the first time. Serum TPO levels and platelet counts were
determined before platelet collection, at the end of apheresis, and for 4 days
thereafter. Serum TPO levels were determined by a TPO-specific enzyme-linked
immunosorbent assay. RESULTS: In relationship to platelet donation, serum TPO
levels showed a temporary increase from baseline levels of 69.2 +/- 7.1 pg per mL
to 117 +/- 6.8 pg per mL 2 days after plateletpheresis (p < 0.05). Further
evaluation revealed a decline in serum TPO levels as platelet counts increased.
Female donors showed a delayed normalization of circulating platelet numbers and
serum TPO levels as compared to male donors. There was no significant correlation
between serum TPO levels and the absolute platelet number during normalization of
the donors' platelet counts after plateletpheresis. CONCLUSION: Single-donor
plateletpheresis results in a temporary increase in serum TPO levels in healthy
platelet donors, which may be part of a compensatory response-boosting
megakaryocytopoiesis after platelet collection.
PMID- 9633558
TI - Measurement of the levels of reticulated platelets after plateletpheresis to
monitor activity of thrombopoiesis.
AB - BACKGROUND: Little is known about the effects of long-term plateletpheresis on
the donors' health. The aim of this study was to examine the effect of
plateletpheresis on the time course of reticulated platelet counts as an estimate
for thrombopoiesis. STUDY DESIGN AND METHODS: The effect of moderate platelet
depletion on the thrombopoietic capacity was evaluated prospectively by the
measurement of reticulated platelets before and after plateletpheresis and on the
following 4 days. Donors undergoing plateletpheresis for the first time were
compared to those donating platelets every other week for more than 18 months.
RESULTS: The median levels of reticulated platelets were significantly lower in
frequent donors than in new donors. In new donors, there was a transient increase
in the median levels of reticulated platelets on Day 3 after apheresis, and
baseline values were reached again on Day 4. On the contrary, in repeat donors,
there was a sustained rise in the percentage of reticulated platelets from Days 1
through 4. However, this increase in reticulated platelet counts was still less
than that seen in new donors. There was no difference in the peripheral blood
platelet counts in the two groups at any time point. CONCLUSION: These findings
suggest that repeat platelet donation might lead to a relative exhaustion of
thrombopoiesis, as evidenced by the low levels of reticulated platelets exhibited
by repeat donors. The reticulated platelet count can be used to monitor the
thrombopoietic capacity of long-term platelet donors.
PMID- 9633559
TI - Release of mediators of systemic inflammatory response syndrome in the course of
a severe delayed hemolytic transfusion reaction caused by anti-D.
AB - BACKGROUND: In vitro studies suggest that mediators of systemic inflammatory
response syndrome are generated in the course of hemolytic transfusion reactions.
Evidence for the in vivo significance of these findings is given by the present
clinical and laboratory analysis of a severe delayed hemolytic transfusion
reaction (DHTR). CASE REPORT: A 67-year-old patient (blood group O, D-negative)
with a negative pretransfusion antibody screen received a massive transfusion
because of arterial bleeding (Day 1). The transfusion of group O, D-positive red
cell concentrates was unavoidable because of limited supplies. At Day 10, the
patient developed a DHTR with symptoms of septic-toxic syndrome and signs of
hemolysis; he received an exchange transfusion. Serologic markers, as well as
proinflammatory and anti-inflammatory mediators, were monitored at the onset of
the DHTR and during the exchange transfusion. RESULTS: At Day 10, the direct
antiglobulin test was positive; anti-D was present, most likely as the result of
an anamnestic immune response. Interleukin (IL)-1 was not detectable; all other
mediators monitored were elevated: IL-1 receptor antagonist, tumor necrosis
factor, IL-6, IL-8, IL-10, neopterin, elastase, C3a-desArg, C-reactive protein,
and fibrinogen. Most of the values declined during the exchange transfusion,
which was followed by an improvement of the clinical presentation. CONCLUSIONS:
Mediators of systemic inflammatory response syndrome were released in the course
of a DHTR caused by anti-D. Severe clinical symptoms could be treated
successfully by exchange transfusion.
PMID- 9633560
TI - The effects of dilution on the outcome of pooled plasma testing with HIV type 1
(HIV-1) RNA genome amplification as compared to the outcome of individual-unit
testing with other HIV-1 markers.
AB - BACKGROUND: Proposed testing of large plasma pools with genome amplification
technology (GAT) for detection of transfusion-transmissible viruses may have
unanticipated complications not associated with individual unit testing. One such
potential complication, the effect of dilution resulting from pool formation, was
the subject of the present study. STUDY DESIGN AND METHODS: Specimens from three
plasma donor HIV type 1 (HIV-1) seroconversion panels were tested with a
quantitative HIV-1 RNA GAT assay (lower detection limit, 400 copies). GAT results
were compared to HIV-1 p24 antigen and anti-HIV-1/2 enzyme immunoassay results.
Effects of dilution on the detection of GAT-positive panel specimens were
assessed by terminal dilution with pooled volunteer-donor EDTA plasma samples.
RESULTS: Low HIV-1 RNA copy numbers (755 and 890 copies/0.1-mL input) that were
detectable in two individual plasma specimens before HIV-1 p24 antigen were
subsequently undetectable by GAT upon dilution with an equal volume of
nonreactive plasma from a single donor. HIV-1 RNA at higher copy numbers (15,500
copies/0.1-mL input) in an HIV-1 p24 antigen-reactive and anti-HIV-1/2
nonreactive specimen was undetectable when diluted to 1-in-50 (1-in-50). Terminal
dilution of seven HIV-1 RNA-containing plasma panel specimens indicated a
proportional loss of HIV-1 RNA detectability with increasing dilution.
CONCLUSION: GAT for detection of HIV-1 RNA in individual specimens was more
sensitive than other HIV markers. For pooled plasma testing, GAT-independent
constraints, such as effects of dilution, may preclude the use of GAT detection
as a replacement for individual unit testing with HIV serologic assays.
PMID- 9633561
TI - Acute normovolemic hemodilution should replace the preoperative donation of
autologous blood as a method of autologous-blood procurement.
PMID- 9633562
TI - Acute normovolemic hemodilution is a legitimate alternative to allogeneic blood
transfusion.
PMID- 9633563
TI - Uses of antithrombin III concentrate in congenital and acquired deficiency
states.
PMID- 9633564
TI - New human leukocyte clusters of differentiation.
PMID- 9633565
TI - Science, lawyers, and "the Europeans": testing requirements in transfusion
medicine.
PMID- 9633566
TI - Factors influencing the availability of umbilical cord blood for banking and
transplantation.
PMID- 9633567
TI - DNA typing of patients with potentially modified patterns in peripheral blood.
PMID- 9633568
TI - Antibody screening for recent Yersinia enterocolitica infection in blood donors.
PMID- 9633569
TI - Intranasal drug use among volunteer whole-blood donors: results of survey C.
PMID- 9633570
TI - Platelet activation and interval between plateletpheresis.
PMID- 9633571
TI - The pathophysiology of UPJ obstruction. Current concepts.
AB - It took more than half of a century for urologists to recognize that
hydronephrosis is not necessarily equivalent to obstruction. Keeping this
important truism in mind, particularly when dealing with antenatal
hydronephrosis, one must also remember that hydronephrosis is not a normal
condition. It is conceivable that although the initial intrinsic stenosis or
ureterovascular obstruction may not be clinically significant in terms of renal
functional damage, as compensatory renal pelvic dilatation develops, secondary
obstructive elements may be recruited to create an insertional anomaly and
peripelvic fibrosis. The individual types of UPJ obstruction that are seen in
diagnostic studies or on the operating table may represent isolated "snapshots"
of evolving pathophysiologic processes. If this is true, patients with
asymptomatic congenital hydronephrosis, although lacking obvious renal function
loss, require long-term follow-up.
PMID- 9633572
TI - Prenatal diagnosis. Therapeutic implications.
AB - Prenatal diagnosis of structural anomalies provides the opportunity to influence
the postnatal outcome. The greatest value of antenatal screening is, in fact, the
awareness of the urogenital abnormalities, such as presumed UPJ obstruction, so
that appropriate investigation and treatment can be offered immediately after
birth and before permanent damage occurs owing to obstruction or infection.
Crombleholme and coworkers reported that prenatal consultation impacted favorably
on outcomes by preventing early termination of pregnancy owing to misconceptions
about the existing condition. It also permitted delivery of complex cases in a
tertiary care setting, thereby preventing a delay in postnatal management. A
systematic approach to the infant in the prenatal and postnatal periods is
important. The natural history of prenatally detected hydronephrosis continues to
be defined, and there is no ideal test to predict the outcome of UPJ obstruction.
Several investigators are evaluating various markers in urine that may help to
identify fetuses who require early postnatal intervention. More complete
understanding regarding the natural history of unilateral pediatric UPJ
obstruction and its response to surgery will not be available until several
randomized, prospective clinical studies are completed. The collaborative effort
of obstetricians, neonatologists, geneticists, radiologists, and pediatric
urologists should provide answers to many questions surrounding prenatally
diagnosed UPJ obstruction.
PMID- 9633573
TI - Neonatal management of unilateral hydronephrosis. Role for delayed intervention.
AB - Hydronephrosis should be managed no differently in the newborn than in any other
age group: UPJ obstruction should be surgically corrected as soon as the
diagnosis is made. Unfortunately, the diagnosis of obstruction in the newborn
with hydronephrosis is difficult and the traditional tests used in the older
child or adult are not valid. Because newborn hydronephrosis is a relatively
benign condition, surgical intervention should be delayed until the diagnosis of
obstruction is proven. A protocol for evaluating the newborn with hydronephrosis
is presented.
PMID- 9633574
TI - Neonatal management. Role for early intervention.
AB - Although performing pyeloplasty on an infant with a relatively healthy kidney
prior to the onset of renal damage is not as well-accepted as "aggressive
observation," the authors argue that early intervention is the more
"conservative" or safe method of treatment for infants with ureteropelvic
junction (UPJ) obstruction. Using experimental and clinical data, the authors
demonstrate that prolonged partial UPJ obstruction in the developing kidney
causes significant renal morbidity with time.
PMID- 9633575
TI - Endourologic options for management of ureteropelvic junction obstruction in the
pediatric patient.
AB - Endourologic intervention is becoming a more widely accepted modality in the
management of pediatric UPJ obstruction. The authors present five factors that
are important in selecting patients that will lead to a successful treatment and
outline techniques for antegrade and retrograde endopyelotomy and balloon
dilation. This article also reviews the recent literature on endourologic
interventions in the management of pediatric UPJ obstruction. The authors
conclude that pediatric endopyelotomy has an 86% success rate and should be
offered as treatment for select pediatric patients with UPJ obstruction.
PMID- 9633576
TI - Ureteropelvic junction obstruction in children. Unique considerations for open
operative intervention.
AB - The treatment of UPJ obstruction in children should be approached in a fashion
that recognizes the differences between children and adults. Radiographic
definition of the urinary tract is different in children than in adults because
of the size of the child and technical difficulties with instrumentation.
Retrograde pyelography, in general, is not necessary in children, although this
decision must be individualized. The surgical incision should be chosen based on
the size of the child and the unique considerations of individual renal anatomy
and pathology, as well as the surgeon's experience. In children, tubeless surgery
may be performed with excellent results, however, diversion with nephrostomies
and stents may be necessary in selected cases. With attention to technical
details and the unique considerations in children, the results of repair of the
UPJ should be excellent and reproducible.
PMID- 9633577
TI - Ureteropelvic junction obstruction in anomalous kidneys.
AB - UPJ obstructions occurring in anomalous kidneys require special consideration.
Many anomalous kidneys are dysmorphic with extrarenal pelves, making the
distinction between obstructed and nonobstructed hydronephrosis crucial. The
radiographic evaluation must be thorough because there are often other associated
anomalies of the ipsilateral or contralateral kidney. Operative intervention must
be tailored to the specifics of the case. Although most UPJ obstructions in
anomalous kidneys can be reconstructed successfully with dismembered pyeloplasty
or treated with newer minimally invasive techniques, issues regarding access,
operative detail, and adjunct procedures make these cases challenging for the
urologic surgeon.
PMID- 9633578
TI - Provocative imaging. Diuretic renography.
AB - Diuretic renography remains the noninvasive functional study of choice in
patients with hydronephrosis resulting from apparent UPJ obstruction. Meticulous
attention to proper patient preparation, radiopharmaceutical selection,
furosemide dosage and administration, and image interpretation and an awareness
of potential pitfalls are essential for accurate diagnosis. For most patients,
the F + 20 protocol is sufficient, however; the F-15 protocol allows
clarification in cases of equivocal baseline F + 20 studies. Invasive antegrade
techniques such as the Whitaker pressure/perfusion test are best reserved for
patients in whom the diagnosis remains equivocal after diuretic renography, or in
patients with massive hydronephrosis or renal insufficiency. New standardized
protocol guidelines should help to ensure studies that are reproducible in
different nuclear medicine laboratories.
PMID- 9633579
TI - Vascular anatomy at the ureteropelvic junction.
AB - In 65% of the cases regarding the ventral surface of the UPJ, there was a
prominent artery, vein, or both in close relation to the ventral surface of the
UPJ. In only 6.8% there was an inferior polar artery crossing anteriorly to the
UPJ. Therefore, many of the vessels visualized close to the UPJ and described as
anomalous and etiologic in obstruction are normal segmental arteries that do not
cause UPJ obstruction. In 26.7% of cases regarding the dorsal surface of the UPJ,
there was a vessel crossing at or lower than 1.5 cm above the posterior surface
of the UPJ. On the basis of our anatomic findings, we advise that in
endopyelotomy, the incision along the stenotic UPJ be created only at its lateral
aspect.
PMID- 9633580
TI - Helical CT and CT angiography for the identification of crossing vessels at the
ureteropelvic junction.
AB - In comparison with pyeloplasty, endourologic procedures for the treatment of
ureteropelvic junction obstruction offer good success rates with less morbidity
and a shorter hospitalization; however, studies have found lower success rates
and increased complications in patients with crossing vessels. Conventional
diagnostic angiography and intravenous urography have both been used to identify
crossing vessels at the UPJ; but, a reliable, less invasive, less costly, and
simpler preoperative procedure to identify crossing vessels is needed. Helical CT
with CT angiography is a promising noninvasive technique for the identification
of crossing vessels at the ureteropelvic junction, which can be used for surgical
planning of endourologic treatment of UPJ obstruction.
PMID- 9633581
TI - Endoureteral sonography to define the anatomy of the obstructed ureteropelvic
junction.
AB - Endoluminal ultrasound of the obstructed ureteropelvic junction (UPJ) provides
accurate anatomic information not available through other studies. Endoluminal
ultrasonography in the evaluation of the obstructed UPJ can be extremely valuable
and its use can be expected to expand with increasing experience with the
techniques. The anatomy demonstrated through the fine resolution of this
technique may ultimately provide the key to the selection of optimal therapy for
the obstructed UPJ.
PMID- 9633582
TI - Endopyelotomy. Prognostic factors and patient selection.
AB - Although clearly a valid alternative to dismembered pyeloplasty for ureteropelvic
junction obstruction in adults, endo(uretero)pyelotomy has not been universally
accepted in the general urologic community because of the 10% to 30% inferior
success rate and the concern regarding hemorrhagic complications. Identification
of prognostic factors for success and complications are therefore of primary
importance. The length of stricture, the grade of hydronephrosis, and the level
of renal function are well recognized prognostic factors. Crossing vessels also
play a role, and in association with the grade of hydronephrosis, they seem to be
a major prognosticator of outcome. With attention to such prognostic factors, and
appropriate patient selection, results can now approach the gold standard of
dismembered pyeloplasty.
PMID- 9633583
TI - Crossing vessels. Endourologic implications.
AB - The controversy regarding the functional significance of vessels crossing at the
ureteropelvic junction is not a new one, though this debate has been resurrected
in recent years because of application of endourologic techniques to manage
ureteropelvic junction (UPJ) obstruction. The principle limitation of endoscopic
treatment of UPJ obstruction is the inferior success rate compared to open
dismembered pyeloplasty. The influence crossing vessels may have in affecting
both the success rates and complications of endoscopic treatment of UPJ
obstruction has yet to be resolved. Crossing vessels may be important for two
reasons: (1) they are a potential source of hemorrhage following endoscopic
incision, and (2) they may play an etiologic role in UPJ obstruction and
therefore may be a reason for failure of endoscopic techniques. This article
reviews some of the historical aspects of crossing vessels and explores recent
studies that are starting to shed some light on this controversial topic.
PMID- 9633584
TI - Retrograde balloon cautery incision of ureteropelvic junction obstruction.
AB - Retrograde balloon endopyelotomy has produced durable success rates of
approximately 80% for all patients with UPJ obstruction. Patients with poor renal
function, high-grade hydronephrosis, or stricture lengths of more than 2 cm fair
worse, and these factors should be considered prior to balloon endopyelotomy. The
debate concerning the functional significance of crossing vessels continues.
However they are probably more important in terms of the risk of postoperative
bleeding than in regards to overall success rates. With the use of endoluminal
ultrasound, angiography, or spiral CT, patients with significant size crossing
vessels can be identified preoperatively. The retrograde approach to UPJ
obstruction using a cutting balloon is a quick and relatively inexpensive
(shorter operative time and hospital stay, and no percutaneous nephrostomy)
method for accomplishing an endopyelotomy incision. With the development of the 5
F balloon catheter and the use of a 7-F post-endopyelotomy stent, the need to
stent the ureter for 7 days prior to the procedure is overcome. In this regard,
the entire retrograde endopyelotomy may be performed in a one-step outpatient
procedure.
PMID- 9633585
TI - Endopyelotomy. Retrograde ureteroscopic approach.
AB - Ureteroscopy is a natural extension of a urologist's practice. This article
describes technical details and results using the ureteroscopic approach to treat
ureteropelvic junction obstruction. With a variety of treatment options
available, this approach compared favorably.
PMID- 9633586
TI - Antegrade endopyelotomy.
AB - Antegrade endopyelotomy has become the procedure of choice for patients with UPJ
obstruction. Overall success rates of 85% can be expected when the procedure is
used in a broad spectrum of patients. Contraindications include an uncorrected
bleeding diathesis, untreated infection, and any anatomic abnormality precluding
safe percutaneous access.
PMID- 9633587
TI - Ureteropelvic junction obstruction and renal calculi. Pathophysiology and
implications for management.
AB - Ureteropelvic junction (UPJ) obstruction is a well-studied phenomenon in terms of
its etiology, implications for renal function, and clinical management. The
presence of concomitant ipsilateral calculus disease, however, introduces a
confounding variable into the understanding of this entity. This article
discusses the relationship between renal calculi and UPJ obstruction as it
pertains to their pathophysiology and clinical management as combined entities.
PMID- 9633588
TI - Laparoscopic pyeloplasty. Indications, technique, and long-term outcome.
AB - Laparoscopic pyeloplasty is one of several minimally invasive treatment options
for UPJ obstruction. In fact, several endoscopically and fluoroscopically
controlled methods of incising the obstructed UPJ are now available that are
significantly less invasive and less morbid in comparison with open pyeloplasty.
However, the long-term success rates of these incisional techniques are less than
the rates reported for open pyeloplasty. Several causes of obstruction may be
present in the primarily obstructed UPJ, including kinking or compression related
to crossing vessels or intrinsic narrowing at the UPJ. One potential reason for
the inferior success rates of incisional methods in comparison with open
pyeloplasty is that the former techniques address the intrinsically narrowed UPJ
but may not address extrinsic problems such as kinking of the ureter associated
with fibrotic bands or compression from crossing vessels. Laparoscopic
pyeloplasty addresses all potential causes of obstruction. Any fibrotic bands
kinking the ureter are divided, and the ureter is spatulated through the level of
the UPJ prior to completion of the anastomosis. If a crossing vessel is
encountered, a dismembered pyeloplasty is performed, the ureter and renal pelvis
are transposed to the opposite side of the vessels, and the anastomosis is
completed. An additional disadvantage of incisional techniques is the significant
risk of hemorrhage following incision of the UPJ, with as many as 3% to 11% of
patients requiring blood transfusion. Hemorrhage may occur owing to an errant
anterior incision, the presence of a crossing vessel, incision into the renal
parenchyma adjacent to the UPJ, or as the result of bleeding from the
percutaneous access site. In contrast, mean estimated blood loss in the authors'
series of 57 laparoscopic pyeloplasties was 139 mL, and none of the patients
required blood transfusion. Although it is more morbid in comparison with
retrograde or fluoroscopically controlled endopyelotomy, laparoscopic pyeloplasty
seems at least comparable to antegrade percutaneous endopyelotomy in terms of the
length of hospitalization and patient convalescence. Laparoscopic pyeloplasty,
however, offers a higher success rate than with incisional techniques, not only
from a radiographic standpoint but from a subjective standpoint as determined by
the results of the analogue pain and activity questionnaire. The major
disadvantage of laparoscopic pyeloplasty is the need for proficiency in
laparoscopic techniques and for a longer operative time. As a result, the
literature on laparoscopic pyeloplasty consists primarily of small series.
Janetschek and co-workers reported on a series of 17 patients who underwent
laparoscopic pyeloplasty, including 14 via a transperitoneal approach and 3 via a
retroperitoneal approach. Procedures performed included ureterolysis alone,
dismembered pyeloplasty, and nondismembered (Fenger) pyeloplasty. "Fenger-plasty"
is similar to Y-V pyeloplasty and is performed by incising the UPJ longitudinally
and closing the incision transversely in a Heineke-Mikulicz fashion. Janetschek
and colleagues reported a 100% success in the eight patients who underwent
dismembered pyeloplasty but believed that this technique was too cumbersome and
should be reserved for patients with long stenoses, dorsally crossing vessels, or
large renal pelvis. Because two of the four patients undergoing ureterolysis
alone failed treatment, Janetschek and colleagues have abandoned this technique.
They now prefer the Fenger-plasty technique, even in the setting of ventrally
crossing vessels, because the technique can be performed quickly with one to
three sutures, and the anastomosis can be sealed with fibrin glue and a flap of
Gerota's fascia. Their experience with this technique, however, remains
relatively limited. Technologic advances such as the Endostitch device have
facilitated reconstructive laparoscopic procedures such as pyeloplasty. (ABSTRACT
TRUNCATED)
PMID- 9633589
TI - Ureteropelvic junction obstruction. Open operative intervention.
AB - The indications to intervene for ureteropelvic junction (UPJ) obstruction have
not changed despite the introduction of newer, less invasive techniques for
definitive management. In contemporary practice, open operative intervention is
still appropriate for those patients in whom alternative management has failed or
is contraindicated, or for those in whom an unobstructed UPJ needs to be assured
with the highest certainty--both immediately and with long-term follow-up.
Although several techniques have been described for open operative reconstruction
of an obstructed UPJ, a dismembered pyeloplasty has proven to be the most
versatile, and should be a part of every urologist's treatment armamentarium.
Alternative primary and salvage techniques for open operative reconstruction of
the UPJ are also described in this article.
PMID- 9633590
TI - Retroperitoneal laparoscopic nephrectomy.
AB - When removal of a kidney is indicated for symptomatic end-stage renal disease of
benign etiology, laparoscopic nephrectomy by the retroperitoneal approach is
increasingly being employed as the technique of choice at many centers. Emerging
data indicate that, in select patients with T1-T3aN0M0 renal tumors < 8 cm,
retroperitoneal laparoscopic radical nephrectomy may be a viable treatment
option.
PMID- 9633591
TI - Unfolding/folding studies on cobrotoxin from Taiwan cobra venom: pH and GSH/GSSG
govern disulfide isomerization at the C-terminus.
AB - Refolding of cobrotoxin was assessed by the exposure degree of its single Trp
determined by an acrylamide quenching study. The change in the accessibility of
Trp for acrylamide quantitatively reflected the formation of folded cobrotoxin,
and the data were confirmed by HPLC and gel electrophoresis analyses. However,
the site-specific information provided by quenching Trp fluorescence revealed
that the ordered structure in the neighborhood of Trp was attained prior to the
complete formation of the tertiary structure of cobrotoxin. HPLC analyses showed
that, in addition to refolded cobrotoxin, two novel species (cobrotoxin II and
cobrotoxin III) with isomerization of disulfide bonds at the C-terminus of the
toxin molecule were produced along the folding reaction. The disulfide pairings
in cobrotoxin II and cobrotoxin III were Cys43-Cys55 and Cys54-Cys60 and Cys43
Cys60 and Cys54-Cys55, respectively. Among the three possible two-disulfide
species at the C-terminus, the disulfide linkages Cys43-Cys60 and Cys54-Cys55 of
cobrotoxin III caused a marked decrease in lethality and resulted in a
conformation which was notably different from that observed with the native toxin
molecule as evidenced by CD spectra. The refolding reaction was accelerated by
the addition of GSH/GSSG, and the resulting products were mostly folded
cobrotoxin. However, if GSH/GSSG was not added into the initial folding
materials, the yields of cobrotoxin II and cobrotoxin III greatly increased. The
conversion of cobrotoxin to its isomers was to be irreversible and pH-dependent:
the higher the pH, the faster the rate of conversion. However, this conversion
could be partly inhibited by GSH/GSSG. Cobrotoxin II and cobrotoxin III were
purified from Taiwan cobra venom as well, and their yields in comparison to that
of cobrotoxin in venom were similar to that noted with the folded products in the
presence of GSH/GSSG. Moreover, the rate of disulfide isomerization was expected
to be slow in venom fluid in which the pH was approximately pH 6.2. Thus, the
finding that cobrotoxin represents the predominant neurotoxin species in Taiwan
cobra venom is probably associated with the synergistic effects of GSH/GSSG and
pH.
PMID- 9633592
TI - Endotoxin pretreatment in vivo increases the mitochondrial respiratory capacity
in rat hepatocytes.
AB - Administration of sublethal doses of endotoxin produces tolerance to subsequent
oxidative stress in diverse animal models. Although endotoxin induces antioxidant
enzymes, particularly manganous superoxide dismutase (Mn-SOD), the phenomenon of
tolerance remains incompletely understood. Previously I determined that endotoxin
treatment in rats increased lung mitochondrial respiration-dependent (i.e.,
independent of Mn-SOD) scavenging of superoxide anion. Because nonenzymatic
scavenging of superoxide anion correlates with the mitochondrial membrane energy
gradient, I hypothesized that endotoxin increases the mitochondrial transmembrane
potential. Endotoxin treatment (500 micrograms/kg intraperitoneally 48 h earlier)
increased the hepatocyte mitochondrial transmembrane potential as determined by
two separate methods: the intramitochondrial sequestration of
triphenylmethylphosphonium (electrical potential or delta psi) and the
fluorescence intensity of the hepatocyte mitochondria when stained with rhodamine
123 and examined by confocal microscopy. These findings suggest that endotoxin
treatment increased the total mitochondrial membrane potential per hepatocyte. In
parallel, endotoxin treatment increased the fluorescence intensity of hepatocyte
mitochondria after staining with 10-N-nonyl-acridine orange, a dye that binds to
the mitochondrial inner membrane independently of the transmembrane potential.
This suggests that an increase in mitochondrial inner membrane mass is
responsible for the net increase in inner membrane potential per cell following
endotoxin pretreatment. These findings complement previous studies in which
endotoxin treatment increased the mitochondrial-specific antioxidant Mn-SOD and
support the more recent finding that endotoxin treatment also increased
nonenzymatic scavenging of superoxide by lung mitochondria. Taken, together,
these observations suggest that mitochondrial biogenesis, and the subsequent
increase in both enzymatic and nonenzymatic scavenging of superoxide anion, is a
central feature of endotoxin-mediated tolerance to oxidative stress.
PMID- 9633593
TI - Oxidation of dilinoleoyl phosphatidylcholine by lipoxygenase 1 from soybeans.
AB - Soybean lipoxygenase-1 is able to oxidize dilinoleoyl phosphatidylcholine at pH
7.5 and 10. The reaction could be followed spectrophotometrically from the
increase of the absorbance at 234 nm. An intermediate product and a final product
were detected. In the intermediate product only one of the linoleoyl chains
(either sn1 or sn2) was oxidized. In the final product, both linoleic acid units
were converted into hydroperoxides. Apparently, oxidation of one of the linoleoyl
chains leads to a disruption of the structure of the mixed bilayer disk, making
the remaining fatty acid unit more accessible to the action of the enzyme. The
specificity of lipoxygenase-1 when acting on phospholipids is not affected by pH.
The exclusive production of 13-hydroperoxyoctadecadienoic acid derivatives of
dilinoleoyl phosphatidylcholine at pH 7.5 and 10 may result from the blockage of
the carboxylic end of the fatty acid.
PMID- 9633594
TI - The fibronectin-like domain is required for the type V and XI collagenolytic
activity of gelatinase B.
AB - Gelatinase B (matrix metalloproteinase-9) is able to degrade several
extracellular matrix proteins, including gelatin, elastin, and collagen types IV,
V, XI, and XIV. This enzyme contains a "fibronectin-like" domain which is
composed of three tandem copies of a fibronectin type 2 homology unit inserted
into its catalytic domain. We have studied the involvement of this domain in the
substrate specificity of gelatinase B by expressing a mutant of the enzyme, in
Escherichia coli, in which this domain has been deleted. This mutant enzyme
retained its ability to cleave the peptide substrate Mca-PLGL(Dpa)AR-NH2,
possessing K(m) and kcat values similar to those of the wild-type enzyme. In
addition, the NH2-terminal, 14-kDa, inhibitory domain of recombinant tissue
inhibitor of metalloproteinase-2 was able to inhibit the mutant and the wild-type
enzymes with the same potency. The mutant's gelatinolytic activity was also
retained but reduced in comparison to that of the wild-type enzyme. However,
contrary to the wild-type enzyme, the mutant was not able to digest or bind
fibrillar collagen types V and XI. These data indicate that the fibronectin-like
domain of gelatinase B is an important determinant of the enzyme's fibrillar
collagen substrate specificity. It allows the enzyme to bind to and cleave
collagen types V and XI, events which are thought to be involved in several
normal physiological and pathological processes such as metastasis and arthritis.
PMID- 9633595
TI - Polysaccharide lyase: molecular cloning of gellan lyase gene and formation of the
lyase from a huge precursor protein in Bacillus sp. GL1.
AB - A bacterium, Bacillus sp. GL1, produced constitutively the extracellular
polysaccharide-degrading enzyme (gellan lyase) with a molecular mass of 140 kDa.
A genomic DNA library of the bacterium was constructed in Escherichia coli using
the cosmid vector, Charomid 9-36. The gene encoding the lyase was cloned by
screening for a gellan-degrading phenotype in E. coli cells and the nucleotide
sequence of the gene was determined. The gene contained an open reading frame
consisting of 7425 base pairs coding a polypeptide with a molecular mass of 263
kDa. The polypeptide contained the same amino acid sequence as N-terminal amino
acid sequence of the enzyme and exhibited no homology with any previously
published protein sequences. E. coli cells transformed with the gene exhibited
gellan lyase activity and produced a protein with a molecular mass of about 260
kDa intracellularly. The protein was purified and shown to have the closely
similar enzymatic properties to those of the native enzyme from Bacillus sp. GL1
with respect to optimal pH and temperature for activity, substrate specificity,
and the mode of enzyme action. These results suggest that, in Bacillus sp. GL1,
gellan lyase is first produced as a huge precursor protein (263 kDa) and then the
protein is posttranslationally processed into extracellular mature form (140 kDa)
through excising C-terminal peptide of about 120 kDa.
PMID- 9633596
TI - Purification and characterization of monomeric lysine decarboxylase from soybean
(Glycine max) axes.
AB - Lysine decarboxylase (EC 4.1.1.18) was purified 364-fold from 2-day-old soybean
(Glycine max) axes. The enzyme was a monomeric protein having a molecular mass of
95,000 Da and an isoelectric point of 4.0. The K(m) for L-lysine was 1.17 mM. The
optimal temperature and pH of the enzyme were 37 degrees C and 7.5, respectively.
Storage of the enzyme at temperature ranging from 0 to 4 degrees C caused a 50%
loss of the activity in 24 h. The enzyme was competitively inhibited by Cl- with
a Ki value of 1.46 mM. However, the activity of the purified enzyme was not
inhibited by F-, Br-, I-, H2PO4-, HPO4(2-), or SO4(2-). Cadaverine at 1 mM
inhibited the enzyme activity by 35%.
PMID- 9633597
TI - Purification, properties, and multiple forms of a manganese-activated inorganic
pyrophosphatase from Bacillus subtilis.
AB - The hydrolysis of magnesium pyrophosphate by inorganic pyrophosphatase from
Bacillus subtilis required its specific, time-dependent, and prior activation by
Mn2+ ions. This was reversed when Mn2+ ions were removed with EDTA. Free Mn2+
ions were not required for catalysis. Pyrophosphatase purified to near
homogeneity gave a single main band of apparent M(r) 36,000 by SDS-PAGE, but of
M(r) 34,000 by matrix-assisted laser desorption ionization-mass spectrometry. The
native enzyme equilibrated at pH 7 between three distinct molecular forms.
Exposure to Mn2+ generated a catalytically active trimer of specific activity
about 5000 mumol pyrophosphate hydrolyzed/min/mg protein. Exposure to EDTA
generated two catalytically inactive forms, a dimer at low ionic strength and a
separate form, of uncharacterized multimeric nature, at molar concentrations of
Na2SO4 or Li2SO4. The latter form was an intermediate in the dimer-trimer
transition caused by addition or removal of manganese ions. Mn2+ reacted with
this "intermediate" form, apparently by reversible association with two
noninteracting binding sites of Kd approximately 0.005 and 0.35 microM,
respectively. The properties of this enzyme may account in part for the unusual
manganese requirements of B. subtilis and related species.
PMID- 9633598
TI - Aldehyde dehydrogenase (CoA-acetylating) and the mechanism of ethanol formation
in the amitochondriate protist, Giardia lamblia.
AB - The so far unelucidated pathway of formation of ethanol, one of the major end
products of the fermentative metabolism of the amitochondriate protist, Giardia
lamblia, was examined. Two NAD-dependent enzymatic activities, an acetaldehyde
dehydrogenase (CoA-acetylating) (EC 1.2.1.10) and an alcohol dehydrogenase (EC
1.1.1.1) were detected. These are assumed to catalyze the formation of ethanol
from acetyl-CoA via acetaldehyde. The first activity, present on a 95-kDa
protein, was purified. It catalyzed the reversible interconversion of acetyl-CoA
to acetaldehyde and CoA-SH with NAD but not NADP as cofactor. In the direction of
aldehyde formation acetyl-CoA was the preferred substrate. Propionyl-CoA and
isobutyryl-CoA were reduced with lower efficiency while succinyl-CoA and benzoyl
CoA were not. In the direction of acyl-CoA formation, acetaldehyde was the
preferred substrate. Propionaldehyde and isobutyraldehyde were utilized at a
lower efficiency while formaldehyde, benzaldehyde, and acetone were not. The
second activity, a primary alcohol dehydrogenase, was also NAD-specific and used
preferentially ethanol as substrate. Sequencing data of peptides from the
purified protein and Northern and Southern analysis indicated that the same
polypeptide, which belongs to the bifunctional aldehyde/alcohol dehydrogenase
enzyme family, carried both activities. These activities define the pathway to
ethanol in G. lamblia as a two step-processes: (i) acetyl-CoA + NADH<-
>acetaldehyde + CoA-SH + NAD+ and (ii) acetaldehyde + NADH<-->ethanol + NAD+. In
contrast to most eukaryotes in which ethanol formation proceeds from pyruvate via
acetaldehyde, the G. lamblia pathway departs from acetyl-CoA, a more distal
product of extended glycolysis.
PMID- 9633599
TI - Reactions of pyridine coenzyme dimers and monomers with viologens.
AB - DCMV++ (1,1'-dimethyl-2,2'-dicyano-4,4'-bipyridinium, bis-methylsulfate) promotes
the aerobic oxidation of the NAD(P) dimers (NADP)2 and (NAD)2 with the formation
of 2 mol of NADP+ or NAD+ per mole of dimers. The reaction appears to follow a
pseudo-first-order kinetics with respect to the dimer concentration. One mole of
oxygen was consumed in the reaction per mole of NAD(P) dimer oxidized and
hydrogen peroxide was produced. The monomers NADPH and NADH under the same
reaction conditions were not oxidized by DCMV++. In anaerobiosis NAD(P) dimers
but not NAD(P)H rapidly reduced DCMV++ to its radical cation DCMV++, which was
rapidly back-oxidized by air to its parent dication. Paraquat (MV++) was also
able to catalyze the aerobic oxidation of NAD(P) dimers and, at a much lower
extent, NADPH and NADH, but only under light irradiation. In anaerobiosis and
upon light irradiation all the above nucleotides were able to convert paraquat to
its radical cation MV++, reoxidized to MV++ by air admission. This study shows
the different ability of NAD(P) dimers and NAD(P)H to undergo one-electron and
two-electron oxidation reactions, with different viologens.
PMID- 9633600
TI - pH dependence of the reaction rate of p-bromophenacyl bromide and of the binding
constants of Ca2+ and an amide-type substrate analog to bovine pancreatic
phospholipase A2.
AB - pH dependence of the chemical reaction rates of p-bromophenacyl bromide (BPB) and
of the binding constants of Ca2+ to bovine pancreatic active- and pro
phospholipases A2 (PLA2s) was studied at 25 degrees C and ionic strength 0.2. The
pH dependence curves of the reaction rates of BPB with both enzymes were
biphasic. The amino acid residues participating in the two transitions were
ascribed to His 48 and the N-terminal alpha-amino group for the active enzyme and
to His 48 and Arg -1 for the proenzyme. The pH dependence curve of Ca2+ binding
to the active enzyme was interpreted in terms of participation of Asp 49, His 48,
and the alpha-amino group. On the other hand, the curve for the proenzyme was
interpreted in terms of participation of Asp 49, His 48, and Arg -1. The Ca2+ and
pH dependence of the binding constant of a potent competitive inhibitor,
monodispersed (R)-2-dodecanoylamino-1-hexanol-phosphocholine (amide-PC), to
bovine pancreatic active-PLA2 was also studied. The binding of amide-PC was
markedly facilitated by Ca2+ binding to the enzyme, whereas that of a genuine
substrate, monodispersed 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC),
was independent of Ca2+ binding. The pH dependence curve of the binding constant
of the amide-PC showed one transition, and this was interpreted in terms of
participation of His 48, whereas the binding of the diC6PC was independent of the
ionization state of His 48. The difference in the Ca2+ dependence for the
bindings of the diC6PC and amide-PC was considered to arise from the fact that
the amide group of amide-PC can form a hydrogen bond with His 48, whereas the
genuine substrate cannot form such a hydrogen bond.
PMID- 9633601
TI - Chromatographic assay and peptide substrate characterization of partially
purified farnesyl- and geranylgeranyltransferases from rat brain cytosol.
AB - A simple method for partially purifying both farnesyltransferase and
geranylgeranyltransferase from rat brain cytosol is presented. Each of the final
protein preparations contains one single transferase activity. A common method of
measurement of both activities is described. The assay, which follows substrate
prenylation, is also convenient for the measurement of the concomitant decrease
in cosubstrates during the two transfer reactions. The quantitative HPLC
detection of the prenylated substrates and of the cosubstrate consumption is used
here to follow the purification processes. The same method is also used for
substrate-specificity studies of the two enzymes performed on 18 synthetic
hexapeptides derived from the C-terminus of proteins known to be prenylated in
vivo. These studies partially confirm the reported differences in the substrate
specificities of the two prenyltransferases. However, the observed recognition of
overlapping sequences by the two enzymes might have important consequences for
the inhibition of either of the enzymes in vivo and for the design of specific
inhibitors.
PMID- 9633602
TI - A conserved tryptophan at the ferredoxin-binding site of ferredoxin:nitrite
oxidoreductase.
AB - Treatment of spinach leaf ferredoxin-dependent nitrite reductase with N
bromosuccinimide (NBS), under conditions where slightly less than 1 mol of
tryptophan is modified per mole of nitrite reductase, inhibits the catalytic
activity of the enzyme by ca. 80% without any effect on substrate binding or
other enzyme properties. Complex formation between nitrite reductase and
ferredoxin completely protects the enzyme against this inhibition. Transient
kinetic measurements show that the second-order rate constant for reduction of
NBS-modified nitrite reductase by reduced ferredoxin is approximately four-fold
larger than that observed for the native, unmodified enzyme. Also, reduction of
NBS-modified nitrite reductase by the 5-deazariboflavin radical shows a different
kinetic pattern than that observed with the native enzyme, suggesting that
tryptophan modification increases access of the radical to the low-potential [4Fe
4S] cluster of the enzyme, decreases the accessibility to the siroheme group of
the enzyme, or both. The tryptophan that is modified has been identified as the
absolutely conserved W92. A methionine, M73, that is also modified by NBS, has
been identified. The ferredoxin-binding site on spinach nitrite reductase thus
appears to include W92 and perhaps M73, in addition to the previously identified
R375, R556, and K436.
PMID- 9633603
TI - An unassembled subunit of NAD(+)-dependent isocitrate dehydrogenase is insoluble
and covalently modified.
AB - The NAD(+)-dependent isocitrate dehydrogenase of Saccharomyces cerevisiae is an
octamer composed of four Idh1p subunits and four Idh2p subunits. Isocitrate
dehydrogenase functions in the tricarboxylic acid cycle and has also been
reported to bind to the 5' nontranslated region of mitochondrially encoded mRNAs.
Mutants defective in either or both of these subunits are unable to grow on the
nonfermentable carbon source, acetate, but will utilize glycerol or ethanol.
Mutant strains lacking Idh2p maintain normal if not elevated levels of
mitochondrial Idh1p. In addition to the mature unassembled Idh1p subunit, a
complex of bands in the 85- to 170-kDa range (Idh1p-Cpx) is observed using NAD
IDH antiserum. Both Idh1p and Idh1p-Cpx are insoluble within the mitochondrion
and are associated with the mitochondrial inner membrane. A histidine-tagged form
of Idh1p was expressed in yeast strains. Chemical amounts of the Idh1p-Cpx could
be purified from strains lacking Idh2p but not from strains containing normal
levels of Idh2p. The data indicate that Idh1p-Cpx is an aggregated and cross
linked form of Idh1p that may be oxidized within the mitochondrion as a
consequence of its aborted assembly.
PMID- 9633604
TI - Di- and oligosaccharide substrate specificities and subsite binding energies of
pig intestinal glucoamylase-maltase.
AB - The substrate specificity of pig intestinal glucoamylase-maltase was
investigated. The alpha-1, beta-2-glycosidic bond of the disaccharide sucrose was
not hydrolyzed. Various substrates with alpha-1,4-glycosidic bonds (maltose,
maltooligosaccharides) were hydrolyzed with high maximal reaction velocities.
Reduction lowered the rate of hydrolysis drastically: k'0 decreases from 75 s-1
for maltose to 3 s-1 for maltitol while the K(m) value increases from 4.2 to 50
mM. Leucrose with alpha-1,5-glycosidic bond was hydrolyzed with a k'0 value of 8
s-1 and a K(m) value of 74 mM. Disaccharides with alpha-1,6-glycosidic bonds were
hydrolyzed with extremely low rates: for isomaltose and isomaltulose k'0 values
of 5 and 3 s-1, respectively, and K(m) values of 90 and 42 mM, respectively, were
observed. Again reduction lowers the k'0 values: The corresponding disaccharide
alcohols alpha-D-glucopyranosyl-1,6-sorbitol and alpha-D-glucopyranosyl-1,6
mannitol, like isomaltooligosaccharides, were not hydrolyzed. Regarding the
conformation of sucrose, leucrose, and maltose previously determined by molecular
dynamics simulations, a reasonable explanation for the different rates of
hydrolysis could be postulated. Based on the enzyme kinetic parameters for the
series of maltooligosaccharides, subsite affinities (A1) according to the subsite
theory were calculated as 7.5 (A1), 17 (A2), 3.4 (A3), and 1.3 kJ/mol (A4) for
subsites 1, 2, 3, and 4, respectively. The intrinsic rate constant k'int was
estimated at 76 s-1.
PMID- 9633605
TI - Structural characterization of the covalent attachment of leukotriene A3 to
leukotriene A4 hydrolase.
AB - Leukotriene A4 (LTA4) hydrolase catalyzes the conversion of the unstable epoxide
LTA4 [5(S)-trans-5,6-oxido-11,14-cis-eicosatetraenoic acid] into proinflammatory
LTB4. During the process of catalyzing this reaction, the enzyme is suicide
inactivated by its substrate. In addition, LTA3, and analogue of LTA4 that lacks
the C14-C15 double bond, is a potent suicide inhibitor of LTA4 hydrolase. We have
synthesized [3H]LTA3 and used this ligand to demonstrate that LTA3 can covalently
label LTA4 hydrolase and that this labeling is specifically competed for by
bestatin and LTA4. Incubation of recombinant human LTA4 hydrolase with LTA3
followed by proteolysis (endoproteinase Lys-C) resulted in a peptide map with a
single modified peptide defining the location of the LTA3 covalent attachment
region. This modified 21-amino-acid peptide had a UV absorption spectrum
corresponding to a conjugated triene chromophore which established conservation
of this structural unit after covalent interaction of LTA3 with LTA4 hydrolase.
MALDI-TOF mass spectrometric analysis of the 21-amino-acid peptide adduct
revealed an abundant MH+ at m/z 2658, consistent with the predicted nominal mass
of the sequenced peptide with the addition of a single LTA3 moiety. Proteolysis
of LTA4 hydrolase modified with LTA3 was performed sequentially with endo-Asp-N
and endo-Lys-C. The resulting peptide isolated by reverse-phase high-performance
liquid chromatography was analyzed by mass spectroscopy revealing two related
peptides, D371-K385 (m/z 2018.0) and D375-K385 (m/z 1577.8), both of which
retained the elements of LTA3. Postsource decay of m/z 1577.8 resulted in an
abundant ion at m/z 536 and an ion of lesser abundance at m/z 856 consistent with
cleavage between V381 and P382 that supported assignment of the modified tyrosine
residue at Y383. These results suggest nucleophilic attack of a tyrosine residue
(Y383) at the conjugated triene epoxide of LTA3 resulting in a triene ether
carbinol covalent adduct.
PMID- 9633606
TI - Tungstate: a potent inhibitor of multifunctional glucose-6-phosphatase.
AB - The insulin-like action of tungstate in diabetic rats (A. Barbera et al., 1994,
J. Biol. Chem. 269, 20047-20053) prompted us to examine the effects of tungstate
on the glucose-6-phosphatase system. Our results indicate that tungstate is a
potent inhibitor of glucose-6-phosphatase, with a Ki in the 10-25 microM range
determined with native microsomes and in the 1-7 microM range determined with
detergent-treated microsomes. With both preparations, simple linear competitive
inhibition was observed versus glucose 6-phosphate (glucose-6-P) as substrate
with the glucose-6-P phosphohydrolase activity of the enzyme. Tungstate was a
simple linear competitive inhibitor versus carbamyl phosphate (carbamyl-P) and a
linear noncompetitive inhibitor versus glucose with the carbamyl-P:glucose
phosphotransferase activity of the glucose-6-phosphatase system. These findings,
in addition to the observation that tungstate protected the enzyme against
thermal inactivation, indicate that tungstate binds with high affinity and
competes at the active site of the enzyme where the substrates glucose-6-P and
carbamyl-P bind prior to catalysis. Our results suggest that potent inhibition of
glucose-6-P hydrolysis by tungstate is likely responsible, at least in part, for
the normalization of glycemia and the rebound in hepatic glucose-6-P levels
observed in earlier studies in which tungstate exhibited insulin-like action in
diabetic rats.
PMID- 9633607
TI - Semisynthetic flavocytochromes based on cytochrome P450 2B4: reductase and
oxygenase activities.
AB - A synthetic flavocytochrome with the reductase and oxygenase activities was
obtained by covalent binding of riboflavin to cytochrome P450 2B4. The reactions
catalyzed by the newly synthesized flavocytochromes were studied. Formation of
carbon monoxide complex with the reduced form of hemoprotein led to 60-80%
inhibition of oxygenase reactions, indicating the leading role of reduced heme
iron in generating active oxygen species by flavocytochromes.
PMID- 9633608
TI - Quantitative trait loci on chromosomes 1 and 4 affect lipid phenotypes in the
rat.
AB - The spontaneously hypertensive rat (SHR/Mol) and the spontaneously diabetic BB/OK
rat were crossed, and the F1 hybrids were backcrossed onto the BB/OK rat in order
to search for quantitative trait loci (QTL) affecting serum total cholesterol and
triglycerides on chromosomes 1, 3, 4, 10, 13, 18, and X. On chromosome 4 a QTL
for triglyceride levels (lod score 3.3) was found within the region flanked by
the D4Mit9 and Il-6 markers. Suggestive linkage (lod score 1.9) was found for
total cholesterol on chromosome 4 at the Spr locus. Also, on chromosome 1
suggestive linkage for both investigated traits was found at marker D1Mit14 (lod
score 1.9 for triglycerides, 2.1 for total cholesterol). The results of the study
could contribute to the explanation of the genetic basis of lipid abnormalities,
which are a common feature of pathological disorders such as coronary heart
disease, hypertension, or non-insulin-dependent diabetes.
PMID- 9633609
TI - Exocytotic stimulation promotes association of the ADP-ribosylation factor with
PC12 cell membranes.
AB - ADP-ribosylation factors (ARFs) are a family of small molecular, monomeric GTP
binding (G) proteins, initially identified by their ability to enhance cholera
toxin (CTX) ADP-ribosyltransferase activity. ARFs have been implicated in protein
transport and vesicle and endosome fusion. Although several reports show that
synthetic peptides of the N-terminus of ARF inhibited Ca(2+)-dependent exocytosis
in permeabilized adrenal chromaffin cells, the role of ARFs in exocytosis has not
been established. In this study, we investigated the translocation of ARFs to the
membrane fraction from the cytosol fraction in PC12 cells after exocytotic
stimulation by measuring the immunoreactivity of ARFs (with anti-ARF anti-serum
and with anti-ARF3 antibodies) and enzymatic ARF activity, which enhances the CTX
effect. Both the immunoreactivity and the enzymatic activity of ARF in the
membrane fraction increased about twofold, significantly, after exocytotic
stimulation with ATP and KCl. The translocation of ARF and noradrenaline release
was observed in the presence of extracellular CaCl2, but not in the absence of
CaCl2. The ARF translocated to the membrane fraction after stimulation in intact
cells seemed to be an inactive, perhaps is the GDP form, because ARF did not
activate CTX in the absence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S).
As previously reported, ARF in the active, GTP gamma S-bound state bound to the
membrane fractions. Thus ARF may have been active during translocation and
inactivated later. The immunoreactivity of Gs alpha, one of the trimeric G
proteins, was not changed before or after stimulation. These findings suggest
that ARFs translocate to membranes from the cytosolic fraction after exocytotic
stimulation in PC12 cells, and raise the possibility that ARFs regulate
exocytosis.
PMID- 9633610
TI - 3,5,3'-triiodothyronine induces mitochondrial permeability transition mediated by
reactive oxygen species and membrane protein thiol oxidation.
AB - Ca(2+)-loaded rat liver mitochondria treated with 3,5,3'-triiodothyronine (T3)
undergo nonspecific inner membrane permeabilization, as evidenced by
mitochondrial swelling, a decrease in membrane potential (delta psi), and an
increase in the rate of oxygen uptake. T3 analogues thyroxine (T4), 3',5'
diiodothyronine (T2), and 3,5',3'-triiodothyronine (reverse T3), in decreasing
order of potency, resulted in a similar but less extensive effect.
Permeabilization induced by T3 is dependent on Ca2+ (1 microM) and T3 (0.5-25
microM) concentrations and is inhibited by cyclosporin A, a known inhibitor of
mitochondrial permeability transition. Catalase or dithiothreitol also prevents
membrane permeabilization, suggesting the participation of membrane protein thiol
group oxidation induced by reactive oxygen species. The determination of the
mitochondrial membrane protein thiol group content after treatment with Ca2+ and
T3 shows a significant decrease, due to thiol oxidation. When mitochondria are
incubated in the presence of inorganic phosphate and the protonophore carbonyl
cyanide p-trifluoromethoxyphenylhydrazone, mitochondrial swelling still occurs
after treatment with T3 and high Ca2+ concentrations, suggesting that
mitochondrial permeabilization is not dependent on T3-induced delta psi or matrix
pH alterations. Under these experimental conditions, when no oxygen is present in
the incubation medium, no permeabilization occurs, suggesting that the
permeabilization is dependent on mitochondrial-generated reactive oxygen species.
Confirming this hypothesis, superoxide generation in a suspension of
submitochondrial particles is increased when T3 is present. Our results lead to
the conclusion that T3 induces a situation of oxidative stress in isolated liver
mitochondria, with Ca(2+)-mediated membrane protein thiol oxidation and
nonspecific inner membrane permeabilization.
PMID- 9633612
TI - Evidence for a protein-protein complex during iron loading into ferritin by
ceruloplasmin.
AB - The formation of a protein-protein complex for the loading of iron into ferritin
by ceruloplasmin was investigated. Ferritin stimulated the ferroxidase activity
of ceruloplasmin unless the ferritin was fully loaded, in which case it inhibited
the ferroxidase activity of ceruloplasmin. The apparent association constant for
the interaction of ferritin and ceruloplasmin was 24 nM. Isothermal titration
calorimetry indicated that the interaction of ceruloplasmin and ferritin was
endothermic, driven by positive changes in entropy. The association constants for
complex formation between ferritin and ceruloplasmin were 4.5 +/- 0.7 x 10(5) and
9.5 +/- 0.3 x 10(4) M-1 for the reduced and oxidized forms of ceruloplasmin,
respectively. The oxidized form of ceruloplasmin was retained on an affinity
column with ferritin immobilized as the ligand and remained bound to the column
with mobile phases of increased hydrophobicity, but was eluted with increased
ionic strength. The ability of ceruloplasmin to remain bound to the affinity
resin was affected by the species from which ceruloplasmin was isolated. Gradient
ultracentrifugation also provided evidence that the two proteins were associated,
since ferritin promoted migration of ceruloplasmin through the gradient.
Including ferrous iron in the gradient resulted in reduction of ceruloplasmin and
increased the mobility of ceruloplasmin with ferritin. These data provide
evidence that ferritin and ceruloplasmin form a protein-protein complex during
iron loading into ferritin, which may limit redox cycling of iron in vivo.
PMID- 9633611
TI - Cross-linking and disulfide bond formation of introduced cysteine residues
suggest a modified model for the tertiary structure of URF13 in the pore-forming
oligomers.
AB - URF13 is a mitochondrially encoded protein in the inner mitochondrial membrane of
maize (Zea mays L.) carrying the cms-T cytoplasm. This protein is responsible for
Texas-type cytoplasmic sterility and is a ligand-gated, pore-forming receptor for
the pathotoxins of fungal pathogens Bipolaris maydis race T and Phyllosticta
maydis. URF13 contains three transmembrane alpha-helices, with amphipathic
helices II and III likely involved in pore formation, and is present as oligomers
in cms-T maize mitochondria and when expressed in Escherichia coli cells. To
study tertiary and quaternary structures of URF13 oligomers, we employed
combinations of site-directed mutagenesis and chemical cross-linking. We
introduced Cys residues individually into consecutive positions 78-82, believed
to be in helix III. We expressed these proteins in E. coli cells and tested for
cross-linking through disulfide bond formation or by using Cys-Cys cross-linkers.
URF13-R79C, URF13-R81C, and URF13-T82C were cross-linked using Cys-Cys-specific
cross-linkers, as were double mutants URF13-C27R/R79C, URF13-C27R/R81C, and URF13
C27R/T82C, indicating that the cross-linking was between introduced Cys residues
on adjacent URF13 molecules. Disulfide bond formation, induced by diamide, was
seen only in URF13-T82C and URF13-C27R/T82C, indicating that Cys residues
introduced into position 82 are closely juxtaposed in the oligomers. Based on
these observations, we modified the models for the secondary structure of URF13
and the tertiary structure of the URF13 oligomers. Sequential cross-linking of
URF13-R81C oligomers with bismaleimidohexane (Cys-Cys cross-linker) and N,N'
dicyclohexylcarbodiimide (Lys-Asp/Glu cross-linker) suggests that URF13 oligomers
consist of an even number of monomers.
PMID- 9633613
TI - Osmolyte strategy in human monocytes and macrophages: involvement of p38MAPK in
hyperosmotic induction of betaine and myoinositol transporters.
AB - Betaine and myoinositol are compatible organic osmolytes which are specifically
accumulated by cells exposed to hyperosmotic medium. A role for compatible
organic osmolytes in the regulation of immune function for rat liver macrophages
has been described recently. This report describes an osmolyte strategy in human
peripheral blood monocytes and human peripheral blood-derived macrophages.
Hyperosmotic (405 mOsm) exposure of monocytes and macrophages led to an
upregulation of betaine/gamma-amino-n-butyric acid (GABA) transporter BGT-1 and
sodium-dependent myoinositol transporter SMIT in mRNA levels within 6 to 12 h.
Induction of BGT-1 and SMIT mRNA occurred regardless of whether hyperosmolarity
was induced by addition of NaCl (50 mM) or raffinose (100 mM). Betaine (5 mM)
inhibited upregulation of BGT-1 as well as SMIT mRNA. After hyperosmotic (405
mOsm) exposure uptake of betaine and myoinositol was increased up to 10-fold
compared to normoosmotic conditions. Hypoosmotic exposure led to a rapid efflux
of betaine and myoinositol. Treatment of cells with the pyridinyl imidazole SB
203580 (10 microM), a specific inhibitor of p38 MAP kinase, inhibited the
hyperosmolarity-induced increase in BGT-1 and SMIT mRNA as well as betaine and
myoinositol uptake by 45-70%. The data show that human peripheral blood monocytes
and human peripheral blood-derived macrophages use betaine and myoinositol are
compatible organic osmolytes when exposed to osmotic stress and that p38MAPK is
involved in hyperosmolarity-induced upregulation of osmolyte transporters BGT-1
and SMIT.
PMID- 9633614
TI - Involvement of the mevalonic acid pathway and the glyceraldehyde-pyruvate pathway
in terpenoid biosynthesis of the liverworts Ricciocarpos natans and Conocephalum
conicum.
AB - The incorporation of 13C-labeled glucose into borneol, bornyl acetate, the
sesquiterpenes cubebanol and ricciocarpin A, phytol, and stigmasterol has been
studied in axenic cultures of the liverworts Ricciocarpos natans and Conocephalum
conicum. Quantitative 13C NMR spectroscopic analysis of the resulting labeling
patterns showed that the isoprene building blocks of the sesquiterpenes and
stigmasterol are built up via the mevalonic acid pathway, whereas the isoprene
units of the monoterpenes and the diterpene phytol are exclusively derived from
the glyceraldehyde-pyruvate pathway. These results indicate the involvement of
both isopentenyl diphosphate biosynthetic pathways in different cellular
compartments.
PMID- 9633615
TI - Guinea pig liver Mu-class glutathione S-transferase M1-2 cross-reacts with
antibodies to both rat Mu- and theta-class glutathione S-transferases.
AB - Two novel major heterodimeric Mu-class glutathione (GSH) S-transferases (GSTs),
designated M1-2 and M1-3*, were isolated from guinea pig (gp) liver cytosol and
purified to homogeneity together with a known major homodimeric Mu-class gpGSTM1
1 (reported as GST b by R. Oshino, K. Kamei, M. Nishioka, and M. Shin, 1990, J.
Biochem. 107, 105-110). These three gpGSTs were quantitatively retained on an S
hexyl-GSH affinity column and separated as homogeneous proteins by
chromatofocusing. Subunits of the heterodimers were inseparable on sodium dodecyl
sulfate-polyacrylamide gel electrophoresis, but could be completely separated by
reverse-phase partition high-performance liquid chromatography. A molecular
cloning study demonstrated that the gpGST subunit M2 consisted of 217 amino acid
residues with a calculated molecular mass of 25,562 and shared 84% identity in
overall amino acid sequence with gpGSTM1-1. N-terminal amino acid sequences of
peptides from the gpGST subunit M3* with a blocked N-terminus strongly suggested
that it should belong to the Mu class. Western blot analysis using antisera
raised against purified rat (r) GSTsA1-2 (Alpha), M1-1, P1-1 (Pi), and T2-2
(Theta) indicated that gpGSTsM1-1 and M1-3* cross-reacted only with anti-rGSTM1
antibody. However, gpGSTM1-2 cross-reacted intensely to almost the same extent
with antibodies to both rGSTsM1-1 and T2-2. A homodimeric gpGSTM2-2, artificially
constructed from native gpGSTM1-2 by treatment with guanidine hydrochloride
followed by dialysis, intensely cross-reacted with antibodies to both the rat Mu-
and Theta-class GSTs. Thus, the gpGST subunit M2 provided the first evidence for
the double immuno-cross-reaction of a GST with polyclonal antibodies to two
different classes of GSTs.
PMID- 9633617
TI - [Use of the micronucleus test in the evaluation of cytogenetic state of persons
living in the polluted area of the Siberian chemical plant].
AB - We have carried out analysis of the number of blood erythrocytes and lymphocytes
with micronuclei in the inhabitants of four settlements located near the place of
the accident, which happened at the atomic power station of the Siberian chemical
plant (Tomsk-7) on April 6, 1993. In all cases, the people examined showed a
considerable increase in the number of cells with micronuclei as compared with
the control. We observed the same people for two years and found a gradual
decrease in the number of cells with micronuclei. It has been shown in this work,
that people born in 1963-1970 have a much higher level of cells with micronuclei,
which we tend to regard as a result of the radiation accident at the Siberian
chemical plant in 1963. The data we have obtained allow us to conclude that
penetration of radionuclides into the human organism in the prenatal and early
postnatal periods can lead to the formation of stable clones of erythroid cells
with micronuclei and a higher level of erythrocytes with micronuclei, which can
remain in the blood for a long time.
PMID- 9633616
TI - [Interactions of inhibitor of free radical reactions and 2-deoxyribosyl
macroradicals].
AB - By steric computer modelling of five types of 2-deoxyribosyl radicals and their
molecular products generated in DNA by radiation as a result of R + InH = RH + In
reaction the displacement of DNA bases (maximum--for C'1 atoms and minimum for
C'3 ones) has been determined. Literature data on the DNA decay in the irradiated
cells, and in DNA frozen solutions as well as the data on radiolysis of compounds
modelling separate DNA fragments allowed to offer a general scheme of the every 2
deoxyribosyl radical transformation and to calculate a balance between the
intermediate and final molecular products (processes) of the 2-deoxyribosyl
radiolysis. The DNA conformation change due to the 2-deoxyribosyl stereoisomers
formation at C'3 and C'4 atoms is discussed as one of the suggested reasons for
genetic radiation mutation.
PMID- 9633618
TI - [Determination of mutation frequency at loci of glycophorin A and T-cell
receptors: informativeness for biological dosimetry of acute and prolonged
irradiation].
AB - The frequencies of somatic mutations at loci of glycophorin A (GPA) and T-cell
receptor (TCR) were determined in persons exposed professionally to ionizing
radiation or a result of accidents at nuclear power plants and in control donors.
Dependence of glycophorin A mutant (NO) cell frequency on doses of acute (up to
3.5 Gy) and prolonged (up to 15.0 Gy) irradiation was shown. The slope of linear
regression corresponded to increase of NO-mutant frequency by 31.1 x 10(-6)/Gy (r
= 0.87, p < 0.0001) for acute irradiation and by 6.3 x 10(-6)/Gy (r = 0.61, p <
0.0001) for prolonged one. The 5-fold decrease of the linear regression slope in
the case of prolonged irradiation makes significantly worse permissive ability of
the GPA test. Therefore its use for biological dosimetry of prolonged irradiation
is not expedient in dose interval up to 1 Gy. The frequency of mutations in genes
of T-cell receptor significantly correlated with dose of irradiation only in
group of donors with recent radiation exposure (r = 0.75, p = 0.0002). Meanwhile,
the TCR method is more sensitive and informative for biological dosimetry of
recent radiation, than the GPA test.
PMID- 9633622
TI - [Effects of prolonged gamma irradiation and hypoxia on bioelectrical activity of
myocardial cells].
AB - It was established that prolonged gamma-irradiation of rats leads to the decrease
of amplitude and duration of action potentials of right atrial cells, attenuation
of the dependence of these electrophysiological characteristics upon the
stimulation frequency, depression of the interval of cardiomyocytes reaction on
the hypoxia. The revealed post-radiation changes determine the reduction of
function resistance of heart cells bioelectrical activity and promote the
initiation of arrhythmias.
PMID- 9633619
TI - [Determination of mutation frequency at loci of glycophorin A and T-cell
receptor: study of Chernobyl AES accident cleanup workers].
AB - The frequencies of somatic mutations at loci of glycophorin A (GPA) and T-cell
receptor (TCR) were determined in control unexposed donors and Chernobyl clean up
workers, who received low doses of irradiation up to 0.25 Gy. High variability of
mutant rates for two investigated genes was shown in the clean up workers. No
significant difference in the GPA (NO) mutant frequencies was observed between
the clean up workers and control donors (p > 0.05), though there is a tendency
for increasing the GPA mutation rate in the clean up workers. Meanwhile, the TCR
mutation rate was significantly increased the clean up workers (p < 0.01),
perhaps because of acceleration of spontaneous mutagenesis and possible genome
instability. Persons with elevated levels of mutations at two loci can present a
group at high risk in respect to oncological diseases.
PMID- 9633621
TI - [Morphological characteristics of central and peripheral organs of rat immune
system in time course of adaptation to external low-dose gamma irradiation].
AB - The morphohistochemical changes in immune system lymphoid organs and skin of
rats, exposed to single and fractionated gamma-radiation (0.35 Gy) were studied
during 1 month. It has been revealed that single irradiation didn't significantly
influence, while the fractionated irradiation in equal dose resulted in lymphoid
cells elimination from thymus and spleen and changes in skin and bone marrow
cells subsets, inducing the increase of lymphoid cells number and activation of
tissue basophils and macrophages reaction.
PMID- 9633620
TI - [Study of physical properties of the apical membrane of enterocytes of rat small
intestine under the effects of ionizing radiation].
AB - The effect of X-ray radiation in doses of 1.0 and 3.0 Gy (1 day after
irradiation) on physical properties of the apical membrane of rat small intestine
enterocytes is studied. It is shown that the fluidity of the bulk lipids doesn't
change but the fluidity of the boundary lipids increases after irradiation. The
data on quenching of the tryptophane fluorescence by pyrene and magnesium ions
indicates apparently the irradiation--induced protein aggregation in membrane.
PMID- 9633625
TI - [Forming of memory (imprinting) in chicks after prior low-level exposure to
electromagnetic fields].
AB - EMF of power density from 0.4 to 10 mW/cm2 can influence forming the memory
(imprinting). Showed the possibility to fix EMF modulated in embryonic brain
during the natal period and conservation of this information after birth.
PMID- 9633624
TI - [Study of immune status indices, levels of alpha-1-thymosin and autoantibodies to
thymic epithelial cells in persons who worked in the 30-kilometer zone of the
Chernobyl AES depending on the radiation dose].
AB - The indices of immune status, concentration of alpha 1-thymosin and level of
thymus epithelial cell autoantibodies in human blood of persons, who had worked
in 30-km zone Chernobyl NPP were studied. The decrease in mean number of
leukocytes, lymphocytes, CD5+, CD4+, CD8+ cells, content of serum alpha 1
thymosin and increased level of autoantibodies were detected in workers, whose
dose rates irradiation were greater than 25 cSv. So, the quality differences in
the changes of immune system, which were induced by low dose chronic irradiation
were obtained.
PMID- 9633623
TI - [Hemo- and immunostimulating effect of an extract from blood cells of the Central
Asian tortoise].
AB - Radiotherapeutic efficacious of the compounds from major organs and tissues of
Central Asian tortoise--the animal known for its unique radioresistance, has been
checked up. Along with the so well-known compounds as the plasma ones, tortoise
spleen extracts (TSE) and the ones from the liver of adult animals and embryos,
extracts from kidneys and muscles have been shown to increase the survivability
rate of irradiated rats and mice. The compound, that called "Tortezin" shows the
highest blood cell cytosol effect. The specific activity and the output are 4 and
12 times higher, than the ones of TSE, respectively. Dose increase factor (DIF)
reaches as far as 1.41. The compound possesses considerable immunostimulating
activity. The detailed physico-chemical characteristics of the compound, quite
sufficient for its identification has been made.
PMID- 9633626
TI - [Features of modifications of cytotoxic consequences of microwave and thermal
heating].
AB - The incubation of bacteria Escherichia coli B/r and Escherichia coli Bs-1,
preliminarily heated by microwave (frequency 7 GHz) or equal usual heat in water
isotonic (0.9%) or hypertonic (10%) solution of sodium chloride resulted in
decrease or increase of the cell lethality independently from heating manner.
Hypertonic solutions of this compound, as was established, protected the cells
against heat damages during the microwave heating less effectively than during
thermal heating.
PMID- 9633627
TI - [Biomedical and economic consequences of stratosphere ozone depletion].
AB - Information on possible human health-changes associated with stratosphere ozone
depletion and amplification factor (% increase of the stick rate by 1% decrease
of ozone) values for acute (erythema, keratitis, cataract, immunosuppression) and
chronic (skin cancer, cataract) effects of natural UV-radiation was analysed.
Amplification factor (AF) values for acute UV-effects increase with degree of
ozone depletion. For degrees less than 12.5% they are independent of latitude and
equal to 1.9 for erythema, 1.3-1.5 for keratitis, 1.7-2.3 for cataract and 0.9
1.1 for immunosuppression. AF values for incidence of non-melanoma skin cancer
are independent of age, higher in males than females, and higher for squamous
cell carcinoma, than for basal cell carcinoma. Their optimal estimations for
whites equal to 2.7 for basal cell and 4.6 for squamous cell carcinoma. AF values
for incidence of cutaneous malignant melanoma range between 1 and 2, for melanoma
mortality--between 0.3 and 2. AF values for incidence of cataract range between
0.3 and 1.2 with optimal estimations between 0.6 and 0.8. Prognosis of non
melanoma skin cancer and cataract incidences, melanoma mortality and economic
loss for different scenarios of stratosphere ozone depletion are presented.
PMID- 9633628
TI - [Dynamics of decrease of the transfer coefficient of Cs-137 to agricultural
plants after the Chernobyl AES accident].
AB - Data on the dynamics of the decrease of 137Cs transfer factors to agricultural
plants after the accident at the ChNPP are presented. The ecological half-life
periods of decrease in transfer factors in the first period after the accident
(1987-1989) have been shown to vary between 1.2 and 2.9 years. Subsequently the
decrease slowed down and in 1990-1994 the half-life periods amounted to 4-11
years depending on plant species peculiarities and soil properties.
PMID- 9633629
TI - Histidine carboxylase of Leuconostoc oenos 9204: purification, kinetic
properties, cloning and nucleotide sequence of the hdc gene.
AB - Histidine decarboxylase (HDC) was purified to homogeneity from Leuconostoc oenos
9204, a wine lactic acid bacterium. Histidine decarboxylase comprised two
subunits, respectively alpha and beta. The hdc gene was cloned and sequenced. The
gene encodes a single polypeptide of 315 amino acids, demonstrating that Leuc.
oenos 9204 HDC was synthesized as a precursor proHDC pi 6 (Mr 205,000). A
cleavage between Ser-81 and Ser-82 generated the alpha (Mr 25,380) and beta (Mr
8840) chains, which suggested that the holoenzyme exists as a hexameric structure
(alpha beta)6. At the optimal pH of 4.8, the HDC activity exhibited a simple
Michaelis-Menten kinetic (K(m) = 0.33 mmol l-1, Vmax = 17.8 mumol CO2 min-1 mg
1), while at pH 7.6 it was sigmoidal (cooperativity index of 2). Histamine acted
as a competitive inhibitor (Ki = 32 mmol l-1). The similarities of these results
with those described for other bacterial HDC support the assumption that the
pyruvoyl enzymes evolved from a common ancestral protein and have similar
catalytic mechanisms. These results also confirmed that the main lactic acid
bacterial species responsible for malolactic fermentation in red wine is able to
produce histamine. Bacteria carrying the HDC activity must be avoided during
selection of strains for the production of malolactic starters.
PMID- 9633630
TI - The effect of essential oils of basil on the growth of Aeromonas hydrophila and
Pseudomonas fluorescens.
AB - Basil essential oils, including basil sweet linalool (BSL) and basil methyl
chavicol (BMC), were screened for antimicrobial activity against a range of Gram
positive and Gram-negative bacteria, yeasts and moulds using an agar well
diffusion method. Both essential oils showed antimicrobial activity against most
of the micro-organisms examined except Clostridium sporogenes, Flavimonas
oryzihabitans, and three species of Pseudomonas. The minimum inhibitory
concentration (MIC) of BMC against Aeromonas hydrophila and Pseudomonas
fluorescens in TSYE broth (as determined using an indirect impedance method) was
0.125 and 2% (v/v), respectively; the former was not greatly affected by the
increase of challenge inoculum from 10(3) to 10(6) cfu ml-1. Results with resting
cells demonstrated that BMC was bactericidal to both Aer. hydrophila and Ps.
fluorescens. The growth of Aer. hydrophila in filter-sterilized lettuce extract
was completely inhibited by 0.1% (v/v) BMC whereas that of Ps. fluorescens was
not significantly affected by 1% (v/v) BMC. In addition, the effectiveness of
washing fresh lettuce with 0.1 or 1% (v/v) BMC on survival of natural microbial
flora was comparable with that effected by 125 ppm chlorine.
PMID- 9633631
TI - Immunodot detection of nisin Z in milk and whey using enhanced chemiluminescence.
AB - A highly specific antisera was produced in New Zealand white rabbits against
nisin Z, a 3400 Da bacteriocin produced by Lactococcus lactis ssp. lactis biovar.
diacetylactis UL 719. A dot immunoblot assay was then developed to detect nisin Z
in milk and whey. As few as 1.5 10(-1) international units per ml (IU ml-1),
corresponding to 0.003 microgram ml-1 of pure nisin Z, were detected in carbonate
bicarbonate buffer within 6 h using chemiluminescence. When milk and whey samples
were tested, approximately 0.155 microgram ml-1 (7.9 IU ml-1) of nisin Z was
detected. The detection limit obtained was lower than that of traditional methods
including microtitration and agar diffusion.
PMID- 9633632
TI - Mathematical modelling of the heat resistance of Listeria monocytogenes.
AB - The heat resistance of Listeria monocytogenes phagovar
2389/2425/3274/2671/47/108/340 (1992 French outbreak strain) in broth was studied
at 55, 60 and 65 degrees C. Experiments were carried out on bacterial cultures in
three different physiological states: cultures at the end of the log phase,
cultures heat-shocked at 42 degrees C for 1 h, and subcultures of cells resistant
to prolonged heating. Survivor curves were better fitted using a sigmoidal
equation than the classical log-linear model. This approach was justified by the
existence of heat resistance distributions within the bacterial populations.
Peaks (log10 of heating time) of heat resistance distributions of untreated, heat
shocked, and selected cultures at 55, 60 and 65 degrees C were 0.34, -0.90 and
1.84 min, 0.74, -0.51 and -1.24 min, and 0.17, -0.94 and -1.45 min, respectively.
The widths of the distributions are proportional to 0.29, 0.36 and 0.41 min0.5,
0.26, 0.36 and 0.41 min0.5, and 0.34, 0.44 and 0.41 min0.5. An increase in the
thermal tolerance could then be induced by sublethal heat shock or by selection
of heat resistant cells.
PMID- 9633635
TI - Sensitivity of food pathogens to garlic (Allium sativum).
AB - The inhibitory activity of garlic (Allium sativum) against Staphylococcus aureus,
Salmonella typhi, Escherichia coli and Listeria monocytogenes was measured by the
'turbidity' method. Minimum inhibitory concentration (MIC) of garlic at 80%
inhibition level was calculated for these bacteria. All bacterial pathogenic
strains tested were inhibited by garlic; E. coli was most sensitive and Listeria
monocytogenes was least sensitive. Therefore, garlic has potential for the
preservation of processed foods.
PMID- 9633634
TI - QSARs for the effect of benzaldehydes on foodborne bacteria and the role of
sulfhydryl groups as targets of their antibacterial activity.
AB - Quantitative structure activity relationships (QSARs) were obtained describing
the activity of a series of benzaldehydes against three different foodborne
bacteria, Listeria monocytogenes F6861, serotype 4b, Salmonella enteritidis,
Phage type 4, P167807 and Lactobacillus plantarum INT.L11. MIC values at pH 6.2
and 35 degrees C were obtained for 11 phenolic benzaldehydes to produce multiple
linear regression and artificial neural network models. For each organism, the
models contained a steric parameter Vw and an electronic-steric parameter for
ortho substituents Es degree. The benzaldehydes did not require to partition to
produce their effect, shown by the lack of a lipophilic parameter in the models.
This strongly suggests that they act on the outside of the cells. Substitution
ortho to the carbonyl group increased their antibacterial action. Cells were
treated with 2,3-dihydroxy benzaldehyde and examined for their ability to bind
radiolabelled iodoacetate to envelope sulfhydryl groups that remained available.
It was shown that the accumulation of radiolabelled iodoacetate was lower after
treatment, indicating possible competition between these two compounds for the
same target. The order of the sensitivity to benzaldehydes (Salmonella > Listeria
> Lactobacillus) correlated with the number of surface sulfhydryl groups
available, being highest for Salmonella.
PMID- 9633637
TI - Colonization of Vibrio pelagius and Aeromonas caviae in early developing turbot
(Scophthalmus maximus L.) larvae.
AB - Polyclonal antisera made in rabbits against whole washed cells of Vibrio pelagius
and Aeromonas caviae were used for detection of these bacterial species in the
rearing water and gastrointestinal tract of healthy turbot (Scophthalmus maximus)
larvae exposed to V. pelagius and/or Aer. caviae. The results demonstrated that
this method is suitable for detection of V. pelagius and Aer. caviae in water
samples and larvae at population levels higher than 10(3) ml-1 and 10(3) larva-1.
Populations of aerobic heterotrophic bacteria present in the gastrointestinal
tract of turbot larvae, estimated using the dilution plate technique, increased
from approximately 4 x 10(2) bacteria larva-1 on day 3 post-hatching to
approximately 10(5) bacteria fish-1 16 days post-hatching. Sixteen days after
hatching, Vibrio spp. accounted for approximately 3 x 10(4) cfu larva-1 exposed
to V. pelagius on days 2, 5 and 8 post-hatching. However, only 10(3) of the
Vibrio spp. belonged to V. pelagius. When larvae were exposed to Aer. caviae on
day 2 post-hatching, the gut microbiota of 5-day old larvae was mainly colonized
by Aeromonas spp. (10(4) larva-1), of which 9 x 10(3) belonged to Aer. caviae.
Later in the experiment, at the time when high mortality occurred, 9 x 10(5) Aer.
caviae were detected. Introduction of V. pelagius to the rearing water seemed to
improve larval survival compared with fish exposed to Aer. caviae and with the
control group. It was therefore concluded that it is beneficial with regard to
larval survival to introduce bacteria (V. pelagius) to the rearing water.
PMID- 9633638
TI - Heat resistance of Listeria monocytogenes in dairy products as affected by the
growth medium.
AB - Listeria monocytogenes strains 1151 and Scott A were grown in broth at 30 degrees
C and transferred to half cream, double cream and butter stored at 5 degrees C to
determine the influence of dairy product composition on heat resistance at 52,
56, 60, 64 and 68 degrees C. Strain 1151 showed a higher heat resistance than
strain Scott A. The heat resistance of both strains was higher in the dairy
products than in broth, particularly at lower temperatures. A significant
difference was observed between log 10 of the D-values in the different dairy
products. The D-values obtained for both strains resuspended in all the dairy
products would result in efficient elimination of the pathogen at 72.7 degrees C
for 15 s. The highest D-value was 11.30 s at 68 degrees C and by using a z-value
of 6.71 degrees C it can be determined that at 72.7 degrees C the D-value would
be 1.5 s. The 15 s process would therefore achieve 10 log reductions. The effect
of growth conditions on the heat resistance at 60 degrees C of L. monocytogenes
Scott A was also investigated. When the cells were grown in the diary products
themselves, and particularly butter, the heat resistance of Scott A was enhanced;
for example, the D-values were 7.15 times higher than in broth. Further studies
are required to investigate if this protection against heating exists at higher
temperatures, in which case the efficiency of pasteurization treatments or other
heat treatments would be considerably lowered.
PMID- 9633640
TI - Polymorphism of Listeria monocytogenes and Listeria innocua strains isolated from
short-ripened cheeses.
AB - Thirty isolates of Listeria monocytogenes and 18 of L. innocua obtained from
different short-ripened cheeses manufactured in Asturias (northern Spain), were
compared with each other and with reference strains using serotype, phage type
and pulsed-field restriction endonuclease digestion profiles analysis of the
total DNA. Restriction enzymes ApaI and SmaI defined five clusters in L.
monocytogenes (m1 to m5) and two main clusters in L. innocua (i1 and i2). Cluster
i2 was further arranged into three subclusters (i2a, i2b and i2c) based on the
different Eco52I (XmaIII) and Crf42I (SacII) patterns of its isolates. Clusters
of L. innocua were clearly different whereas those of L. monocytogenes were more
closely related to each other. In this latter species, serotype 4b isolates (m4
and m5) constituted a more homogeneous group than serogroup I isolates (m1, m2
and m3). Cluster m3 contained two strains of serotype 1/2a whereas m1 and m2
harboured strains of both serotypes, 1/2a and 1/2b. Therefore, the combined use
of restriction patterns and serotype may be useful to differentiate L.
monocytogenes strains showing identical restriction profiles but differing in
serotype. The cheese source of Listeria strains proved that isolates from cluster
m1 were repeatedly detected as a contaminant in the same type of cheese.
Comparison of L. monocytogenes ApaI profiles showed a genetic proximity of m4 and
m5 to the recognized pathogenic strains ATCC 13932 and NCTC 11994, responsible
for meningitis cases in other countries. Finally, bacteriophage typing data
indicated that m4, the sole phage typable group, had a phage type resembling that
of strains causing the Auckland (New Zealand) outbreak of listeriosis in 1969.
These data suggest a wide distribution of closely related types which might
cause, under several circumstances, sporadic cases of listeriosis.
PMID- 9633641
TI - Biocidal activity in plant pathogenic Acidovorax, Burkholderia, Herbaspirillum,
Ralstonia and Xanthomonas spp.
AB - Antibacterial and antifungal activity was investigated for strains of Acidovorax
spp., Burkholderia spp., Herbaspirillum rubrisubalbicans and Ralstonia
solanacearum; strains representing 118 species and pathovars of Xanthomonas were
also tested for phytotoxic capacity. Antibacterial activity was present in all
Burkholderia spp. except B. andropogonis, in biovars II and III of R.
solanacearum but not in biovars I and IV, and in two strains of Xanthomonas.
Little antibacterial activity was recorded for Acidovorax spp. Antifungal
activity was expressed by most strains of A. avenae ssp. avenae and A. avenae
ssp. cattleyae. Weak or variable antifungal reactions were given by strains of A.
avenae ssp. citrulli and no activity was expressed by A. konjaci. Most strains of
B. caryophylli, B. cepacia, B. gladioli pv. agaricicola, B. gladioli pv.
alliicola, B. gladioli pv. gladioli, B. glumae and B. plantari produced extensive
inhibition zones against Rhodotorula mucilaginosa. Strains of H. rubrisubalbicans
and R. solanacearum gave negative, weak or variable reactions. Strains of
Xanthomonas spp. exhibited no antifungal activity. In all cases antifungal
activity was caused by a low molecular weight toxin. Three Xanthomonas strains
exhibited phytotoxic activity. The ecological implications of these data are
discussed.
PMID- 9633642
TI - Detection of pathogenic Yersinia enterocolitica using a digoxigenin labelled
probe targeting the yst gene.
AB - A 145 base pair digoxigenin-d-UTP-labelled probe, specific for pathogenic
Yersinia enterocolitica heat-stable enterotoxin yst gene, was prepared by PCR.
The probe was used in DNA-DNA colony hybridization and dot-blot hybridization
assays. The specificity of the probe was confirmed using 52 strains representing
all Yersinia spp., except Y. pestis. Out of a total of 25 Y. enterocolitica
strains screened, the probe correctly identified all 18 pathogenic strains. Among
the other Yersinia spp. screened, only one strain of Y. kristensenii was
positively detected by the yst probe but could be differentiated by its weak
signal response as compared with that obtained by pathogenic strains of Y.
enterocolitica.
PMID- 9633643
TI - Heterogeneity of plant-associated streptococci as characterized by phenotypic
features and restriction analysis of PCR-amplified 16S rDNA.
AB - Thirty-five strains of streptococci isolated from forage grasses were examined by
restriction analysis of PCR-amplified 16S rDNA. Using a set of seven
endonucleases, five 16S rDNA genotypes were obtained. The isolates could be
identified as belonging to the species Enterococcus faecium, Ent. mundtii, Ent.
faecalis, Ent. casseliflavus and Lactococcus lactis ssp. lactis, respectively. To
assign the isolates to one of these species, digestion with the endonuclease
HinfI was sufficient. Data obtained from whole-cell protein analysis were in
accordance with the species identification. Additionally, three of the five
species found were subdivided into two related subgroups. Both methods are
suitable for a rapid and unequivocal identification of plant-associated
streptococci. The phenotypic characters showed a high diversity and were in some
cases contrary to the expected features usually given in genus and species
descriptions. The results demonstrated the close relatedness of the determined
species in contrast to their high phenotypic heterogeneity.
PMID- 9633645
TI - Development of a risk assessment for BSE in the aquatic environment.
AB - Bovine spongiform encephalopathy (BSE) is believed to be transmitted by the
ingestion of proteinaceous agents called prions which accumulate in the brain and
spinal cord of infected bovines. Concern has been expressed about the risks of
transmission of BSE to humans through BSE prions discharged to the aquatic
environment from rendering plants, abattoirs and landfills. The disease-related
form of the prion protein is relatively resistant to degradation, and infectivity
decays rather slowly in the environment. Levels of disinfection used for drinking
water treatment would have little effect. This paper presents the assumptions
which were used to model the risks from a rendering plant disposing of cull
cattle carcasses in the catchment of a chalk aquifer which is used for a drinking
water abstraction. The risk assessment approach focused on identifying the
hydrogeological and physical barriers which would contribute to preventing BSE
infectivity gaining entry to the aquifer. These barriers included inactivation of
BSE agent by the rendering process, removal from the effluent by treatment at the
plant, filtration and adsorption in the clay and chalk, and dilution in the
ground water. The importance in environmental risk assessment of the cow-to-man
species barrier is considered. Two key conclusions about the environmental
behaviour of the BSE agent are that prion proteins are 'sticky' and bind to
particulates, and that the millions of BSE prion molecules comprising a human
oral ID50 are subject to some degree of dispersion and hence dilution in the
environment. Assuming the rendering plant processes 2000 cull cattle carcasses
per week, the risks to drinking water consumers were estimated to be remote.
Indeed, even using worst case assumptions an individual would have to consume 21
d-1 of tap water for 45 million years to have a 50% chance of infection through
drinking water drawn from the aquifer.
PMID- 9633646
TI - Radiation inactivation of some food-borne pathogens in fish as influenced by fat
levels.
AB - The influence of low (0.39-1.1%), medium (4.25%) and high (7.1-32.5%) fat levels
in fish on radiation inactivation of four food-borne pathogens was investigated.
Cells of Listeria monocytogenes 036, Yersinia enterocolitica F5692, Bacillus
cereus and Salmonella typhimurium at logarithmic phase were inoculated in 10%
fish homogenates and subjected to gamma irradiation at ice temperature (0-1
degree C) with doses ranging from 0.05 to 0.8 kGy. The radiation survival curves
of L. monocytogenes and B. cereus were characterized by shoulders, while a
tailing effect was depicted by cells of Y. enterocolitica and B. cereus. The D10
values in kGy calculated on the exponential part of the curve ranged from 0.2 to
0.3, 0.15 to 0.25, 0.1 to 0.15 and 0.09 to 0.1 for L. monocytogenes 036, B.
cereus, Salm. typhimurium and Y. enterocolitica F5692, respectively. This order
(D10) of radiation resistance of each organism was not affected by the fat
content of the fish. Inoculated pack studies carried out separately with each
pathogen in fatty (Indian sardine, 7.1%) and lean (Golden anchovy, 0.39%) fish
showed no difference in their survival after exposure to 1 kGy and 3 kGy doses,
which corroborated the above observation. The practical significance of these
results in the application of the technology is discussed.
PMID- 9633647
TI - Characterization of axenic Pseudomonas fragi and Escherichia coli biofilms that
inhibit corrosion of SAE 1018 steel.
AB - Corrosion inhibition of SAE 1018 steel by Pseudomonas fragi and Escherichia coli
biofilms has been evaluated using batch cultures in rich medium (LB) and seawater
mimicking medium (VNSS) at 23 degrees C and 30 degrees C with or without daily
medium replenishment. Biofilm components have been stained simultaneously for
polysaccharide (calcofluor) and live and dead cells (Live/Dead Baclit viability
kit) and visualized using confocal scanning laser microscopy (CSLM). Image
analysis was used to quantify the relative proportions of live cells, dead cells,
polysaccharide and void space in the biofilm. This staining technique and
examination of the architecture of biofilms responsible for inhibiting metal
corrosion revealed that both Ps. fragi and E. coli produce polysaccharide only in
the seawater medium; in rich medium, the biofilm consisted mainly of a layer of
sessile cells near the biofilm-metal interface and sparse thick clumps of cells
at the biofilm-liquid interface. Biofilms of both strains had a higher proportion
of live cells in the rich medium than in the seawater-mimicking medium at the
higher temperature, and more live cells were present at the higher temperature
for LB medium. The corrosion inhibition observed (2.3-6.9-fold in 8 d) was not
significantly affected by medium type or replenishment. Increase in the cellular
content of the biofilms, as a result of increasing temperature, led to a
reduction in corrosion.
PMID- 9633648
TI - delta-Endotoxin proteins associated with spherical parasporal inclusions of the
four Lepidoptera-specific Bacillus thuringiensis strains.
AB - Four Lepidoptera-specific reference strains of Bacillus thuringiensis, belonging
to serovars sumiyoshiensis (H3a:3d), fukuokaensis (H3a:3d:3e), darmstadiensis
(H10a:10b) and japonensis (H23), which produce spherical parasporal inclusions,
were examined for comparative characterization of delta-endotoxins. SDS-PAGE
profiles of the alkali-solubilized parasporal inclusions revealed the presence of
single major protein bands of 130 kDa in the four strains. Chymotrypsin and
trypsin treatment of the proteins gave profiles different from those of the
strains HD-1 (serovar kurstaki, H3a:3b:3c) and T84 A1 (serovar sotto, H4a:4b).
Also, minor variations were observed in proteolysis profiles among the four
strains. The LC50 values of purified parasporal inclusions for the silkworm
(Bombyx mori) larvae were 7.35, 6.45, 3.08 and 2.63 micrograms g-1 diet,
respectively, showing that their toxicity levels were 5-15 times lower than that
of the strain HD-1 (0.49 microgram g-1 diet). Analysis by immunodiffusion and
immunoblotting with polyclonal antisera revealed that parasporal inclusion
proteins of the four strains are highly related, whereas they shared few or no
common antigens with those of the strains HD-1, T84 A1 and Buibui (serovar
japonensis).
PMID- 9633649
TI - Effect of glucose on glycerol metabolism by Clostridium butyricum DSM 5431.
AB - The levels of 1,3-propanediol dehydrogenase and of the glycerol dehydrogenase in
Clostridium butyricum grown on glucose-glycerol mixtures were similar to those
found in extracts of cells grown on glycerol alone, which can explain the
simultaneous glucose-glycerol consumption. On glycerol, 43% of glycerol was
oxidized to organic acids to obtain energy for growth and 57% to produce 1,3
propanediol. With glucose-glycerol mixtures, glucose catabolism was used by the
cells to produce energy through the acetate-butyrate production and NADH, whereas
glycerol was used chiefly in the utilization of the reducing power since 92-93%
of the glycerol flow was converted through the 1,3-propanediol pathway. The
apparent K(m)s for the glycerol dehydrogenase was 16-fold higher for the glycerol
than that for the glyceraldehyde in the case of the glyceraldehyde-3-phosphate
dehydrogenase and fourfold higher for the NAD+, providing an explanation for the
shift of the glycerol flow toward 1,3-propanediol when cells were grown on
glucose-glycerol mixtures.
PMID- 9633650
TI - The microstructure and distribution of micro-organisms within mature Serra
cheese.
AB - The distribution of micro-organisms in mature Serra, a traditional Portuguese
cheese made from unpasteurised ewes' milk without added starter culture, was
examined by light microscopy and electron microscopy. Four populations of micro
organisms were recognized according to their position within the cheese: (i)
those present as apparently axenic colonies within the curd matrix; (ii) bacteria
growing along curd junctions; (iii) yeasts and bacteria present in the smear on
the surface of the cheese and (iv) bacteria found in cracks which penetrated the
outer part of the cheese from the rind. Two types of crystals were observed,
together with contaminants of vegetable origin and somatic cells originating from
the milk.
PMID- 9633651
TI - A new method for determining the minimum inhibitory concentration of essential
oils.
AB - A new microdilution method has been developed for determining the minimum
inhibitory concentration (MIC) of oil-based compounds. The redox dye resazurin
was used to determine the MIC of a sample of the essential oil of Melaleuca
alternifolia (tea tree) for a range of Gram-positive and -negative bacteria. Use
of 0.15% (w/v) agar as a stabilizer overcame the problem of adequate contact
between the oil and the test bacteria and obviated the need to employ a chemical
emulsifier. A rapid version of the assay was also developed for use as a
screening method. A comparison of visual and photometric reading of the
microtitre plates showed that results could be assessed without instrumentation;
moreover, if the rapid assay format was used, rigorous asepsis was not necessary.
Accuracy of the resazurin method was confirmed by plate counting from microwells
and MIC values were compared with results obtained using an agar dilution assay.
The MIC results obtained by the resazurin method were slightly lower than those
obtained by agar dilution.
PMID- 9633652
TI - Rapid identification of diverse Campylobacter lari strains isolated from mussels
and oysters using a reverse hybridization line probe assay.
AB - Campylobacters isolated from mussels and oysters in The Netherlands were analysed
by a novel assay, based on DNA amplification with primers, based on semiconserved
GTP-binding sites of a putative GTPase gene. Polymerase chain reaction (PCR) was
followed by a single step reverse hybridization line probe assay (PCR-LiPA). This
permits identification of Campylobacter jejuni, C. coli, C. lari and C.
upsaliensis. Among a group of 44 isolates, three C. jejuni, one C. upsaliensis,
one double infection with C. jejuni and C. coli, and 38 C. lari strains were
identified. These results were in complete agreement with conventional
identification methods and whole cell protein analysis. One C. hyointestinalis
isolate was not identified by the PCR-LiPA, since the reverse hybridization assay
does not comprise specific probes for this particular species. PCR products from
36 C. lari isolates were sequenced and phylogenetic analysis revealed the
presence of two major C. lari subgroups: one comprised 11 highly homologous
sequences, whereas the 25 sequences in the other subgroup were more
heterogeneous. This confirmed earlier findings that C. lari isolates comprise a
more heterogeneous group of isolates as compared with C. jejuni, C. coli and C.
upsaliensis. Based on the sequence information, a novel PCR-LiPA was developed
that permits specific and rapid detection of the different C. lari variants.
PMID- 9633653
TI - The survival and growth of acid-adapted mesophilic pathogens that contaminate
meat after lactic acid decontamination.
AB - Lactic acid decontamination (LAD) may adapt pathogens to lactic acid. Such
organisms may have an increased resistance to acid and can contaminate meat after
LAD. The survival and growth of acid adapted Campylobacter jejuni, Salmonella
typhimurium. Escherichia coli O157:H7 and Staphylococcus aureus inoculated on
skin surface of still warm pork belly cuts 2 h after LAD was examined during
chilled (4 degrees C) storage and refrigeration abuse equivalent to 12.5 degrees
C. Lactic acid decontamination included dipping in 1, 2 or 5% lactic acid
solutions at 55 degrees C for 120 s. Lactic acid decontamination brought sharp
reductions in meat surface pH, but these recovered with time after LAD at
approximately 1-1.5 pH units below that of water-treated controls. A sharp
decrease in the number of cfu of pathogens occurred on chilled 2-5% lactic acid
treated pork belly cuts when the skin surface was less than pH 4.8-5.2. The
reductions ranged from 0.1-0.3 log10 cfu cm-2 for E. coli O157:H7 to over 1.7-2.4
log10 cfu cm-2 for Camp. jejuni, respectively. Increase in storage temperature
from 4 to 12.5 degrees C reduced delayed decrease in numbers of all pathogens
except Camp. jejuni by a factor of two. Deaths in Camp. jejuni at 12.5 degrees C
slightly exceeded those at 4 degrees C. After the initial sharp decline, the
number of cfu of mesophilic pathogens decreased gradually at a rate similar to
that on water-treated controls. Growth of all mesophilic pathogens except Camp.
jejuni on 2-5% LAD meat occurred during storage at 12.5 degrees C when the meat
surface pH exceeded 4.8-5.2, and was slower than on water-treated controls. Low
temperature and acid-adapted E. coli O157:H7, Salm. typhimurium and Staph.
aureus, and acid adapted Camp. jejuni that contaminate skin surface after hot 2
5% LAD, did not cause an increased health hazard, although microbiota and
intrinsic parameters (lactic acid content, pH) were created that could advantage
their survival and growth.
PMID- 9633654
TI - Purification and characterization of thermophilin T, a novel bacteriocin produced
by Streptococcus thermophilus ACA-DC 0040.
AB - ACA-DC 0040 produced an antimicrobial agent, which was named thermophilin T,
active against several lactic acid bacteria strains of different species and food
spoilage bacteria, such as Clostridium sporogenes C22/10 and Cl. tyrobutyricum
NCDO-1754. The crude antimicrobial compound is sensitive to proteolytic enzymes
and alpha-amylase, heat-stable (100 degrees C for 30 min), resistant to pH
exposure at pH 1-12 and demonstrates a bactericidal mode of action against the
sensitive strain Lactococcus cremoris CNRZ-117. The production of bacteriocin was
optimized approximately 10-fold in an aerobic fermenter held at constant pH 5.8
and 6.2. Ultrafiltration experiments with culture supernatant fluids containing
the bacteriocin, and further estimation of molecular weight with gel filtration
chromatography, revealed that bacteriocin in the native form has a molecular
weight in excess of 300 kDa. SDS-gel electrophoresis of partially purified
thermophilin T showed that bacteriocin activity was associated with a protein
band of approximately 2.5 kDa molecular mass.
PMID- 9633655
TI - Improved detection of bacteria by flow cytometry using a combination of antibody
and viability markers.
AB - A proprietary fluorogenic marker for cell viability (Chemchrome) was investigated
for the detection of bacteria using flow cytometry. This marker was used in
combination with fluorescently labelled monoclonal antibodies (against Salmonella
typhimurium). Owing to the former's broad band emission spectrum, it was
necessary to use the novel dye RED613 for the antibodies. This combined protocol,
being sensitive only to the live Salm. typhimurium cells, reduced errors due to
intrinsic fluorescence and non-specific binding. Detection of the order of 100
cells ml-1 was achieved in 30 min. This level was achieved even in the presence
of large numbers of non-target or dead organisms.
PMID- 9633657
TI - Characterization of natural isolate Lactobacillus acidophilus BGRA43 useful for
acidophilus milk production.
AB - Lactobacillus acidophilus BGRA43 was selected from a set of human origin isolates
of Lact. acidophilus strains for the highest growth rates and antagonistic effect
against both Gram-positive and Gram-negative bacteria. The strain BGRA43 also
exhibited an inhibitory effect on the growth of Clostridium sporogenes.
Inhibition of this strain seems to be due to lactic acid production rather than
hydrogen peroxide or bacteriocin. Growth of Lact. acidophilus BGRA43 in non-fat
skim milk for 6 h at 37 degrees C resulted in a lowering of the pH value to 4.53.
Besides the fast acidification, this strain generated a high viscosity of skim
milk. These characteristics make the strain BGRA43 attractive for acidophilus
milk production. Lactobacillus acidophilus BGRA43 produces an extracellular
proteinase. Whole cells efficiently degraded casein for 3 h at 37 degrees C
especially alpha- and beta-casein fractions. Total DNA isolated from the strain
BGRA43 did not show any hybridization with lactococcal proteinase probes
indicating that this strain produces a distinctive proteinase.
PMID- 9633656
TI - Development and use of a multiplex PCR system for the rapid screening of heat
labile toxin I, heat stable toxin II and shiga-like toxin I and II genes of
Escherichia coli in water.
AB - Enterotoxigenic Escherichia coli (ETEC) may produce heat-labile toxin (LT) I and
LTII and heat-stable toxin (ST) I and STII, while shiga toxin producing E. coli
(STEC) strains, including enterohaemorrhagic E. coli (EHEC), may produce shiga
like toxin (SLT) I and/or SLTII. Both ETEC and STEC are pathogenic to humans,
pigs and cattle. As contamination of environmental water by any of these
pathogenic E. coli cells is possible, a multiplex polymerase chain reaction (PCR)
system for the rapid screening of LTI, STII, and SLTI and SLTII genes of E. coli
was developed. The PCR primers used were the SLTI and SLTII genes specific
primers developed by the present authors and the LTI and STII genes specific
primers reported by other laboratories. The detection specificity of this
multiplex PCR system was confirmed by PCR assay of ETEC, STEC and other E. coli
cells as well as non-E. coli bacteria. Its detection limit was 10(2)-10(3) cfu
each of the target cells per assay. When this multiplex PCR system was used for
the rapid screening of LTI, STII ETEC and STEC in water samples such as tap,
underground and lake waters, it was found that after the enrichment step, as few
as 10(0) cells 100 ml-1 of the water sample could be detected. Therefore, this
PCR system could be used for the rapid monitoring of ETEC and/or STEC cells
contaminating water samples.
PMID- 9633658
TI - Characterization of Lactobacillus sake isolates from dry-cured sausages by
restriction fragment length polymorphism analysis of the 16S rRNA gene.
AB - Lactobacillus sake strains originally isolated from dry-fermented sausages were
characterized by phenotypic and genotypic methods, including DNA-DNA
hybridization, restriction fragment length polymorphism (RFLP), and 16S rDNA
sequencing analysis, in order to establish their taxonomic position and relation
to well defined reference species. Initially, isolates of Lact. sake showing a
characteristic phenotype (melibiose-positive, maltose- and arabinose-negative)
were identified by DNA-DNA hybridization. Subsequently, RFLP studies using EcoRI
and HindIII as restriction enzymes, and cDNA from Escherichia coli or 16S rDNA
from Lact. sake strains as probes, showed distinct polymorphism levels. Thus,
EcoRI-digested DNA probed with cDNA from E. coli disclosed the presence of a
unique cluster for the meat isolates tested, allowing their differentiation from
the reference type strain. When HindIII-digested DNA was hybridized with the cDNA
probe, strain-specific patterns were obtained, showing a higher discrimination
power. Considerable strain differentiation was also observed when EcoRI and
HindIII digests were hybridized with 16S rDNA probes. Finally, sequence analysis
of the 16S rDNA from one isolate also revealed a certain degree of genetic
variability with respect to the reference strain of Lact. sake.
PMID- 9633659
TI - Bacterial-fungal biofilms in flowing water photo-processing tanks.
AB - A complex seven species model community, including bacteria and fungi, was
selected from organisms isolated from the walls of an industrial flowing water
system. Growth rates of the species were determined in single and mixed batch
culture growth. The rates were found to be significantly higher in mixed culture
for Pseudomonas alcaligenes and Flavobacterium indologenes and higher in single
culture for Xanthomonas maltophilia, Rhodotorula glutinis and Fusarium solani,
whereas no significant difference was recorded for Alcaligenes denitrificans and
Fusarium oxysporum. All species attached to PVC in single and mixed culture to
form biofilms. Xanthomonas maltophilia, Alc. denitrificans, Ps. alcaligenes and
F. solani biofilm cell densities cm-2 were significantly higher than attachment
of the component species in mixed culture. Statistical analyses showed a
significant difference in rate of colonization between single and mixed cultures
for some species. No significant difference was noted between mixed culture cell
densities cm-2 at laminar flows of Reynolds number 2.7 and 5.4.
PMID- 9633660
TI - Water quality in rural Australia.
AB - Grab samples of drinking water collected from reservoirs and from creeks flowing
over pristine land, farmland or land having mixed use were analysed for their
physicochemical and microbiological characteristics. A significant difference
between sites for conductivity and sites for pH was noted using a two-way ANOVA.
No significant interactions were detected between any of the other parameters:
Giardia, Cryptosporidium, Escherichia coli, coliforms, plate count, turbidity or
rainfall.
PMID- 9633661
TI - Sensitivity to commercial disinfectants, and the occurrence of plasmids within
various Listeria monocytogenes genotypes isolated from poultry products and the
poultry processing environment.
AB - The European Suspension Test was used to assess the relative resistance of 19
individual Listeria monocytogenes genotypes, isolated from the poultry processing
environment, to three commercially used disinfectants employed in the plant at
the time of their isolation. To establish the relative resistance between the
strains, the concentration of each disinfectant was reduced until inter-strain
variation became apparent. For Darasan 214 and 7058, variation was detected at
0.1% and 0.5% v/v, respectively, while Daraclean 7361 had to be reduced to only
2.5% v/v. At these concentrations, the mean microbiocidal effect (ME) of each
disinfectant ranged between 4.3 and 3.1 log10 reduction in cfu ml-1. Significant
differences between the strains were obtained with respect to their resistance to
the disinfectants employed (P < 0.01), but the overall log10 reduction for
genotypes 'A1' and 'A2', which were found to persist in the poultry processing
environment, were not found to be significantly different from the genotypes
which had been isolated on a more sporadic basis (P > 0.05). The L. monocytogenes
strains fell into four groups with respect to incidence and size of plasmids
isolated. The first group contained strains which carried two plasmids (5 and 40
MDa) and the other three (groups 2, 3 and 4) comprised strains which carried a
single plasmid (14, 47 and 52 MDa, respectively). There was no correlation
between persistent and sporadic strains with respect to incidence and size of
plasmids isolated. Moreover, the strains which carried no plasmids were found to
be as resistant to the disinfectants as those which did carry plasmids,
suggesting that the plasmids isolated did not confer resistance of L.
monocytogenes planktonic cells to the disinfectants tested. Therefore, it is
unlikely that the strains which had been found to persist in the poultry
processing environment did so by means of plasmid-mediated resistance to the
commercial disinfectants used.
PMID- 9633662
TI - Evaluation of the extent and type of bacterial contamination at different stages
of processing of cooked ham.
AB - In an attempt to determine the composition and origin of the spoilage flora of
refrigerated vacuum-packed cooked ham, the changes in microbial numbers and types
were followed along the processing line. Results revealed Lactobacillus sake and
Leuconostoc mesenteroides ssp. mesenteroides as the major causative agents of
spoilage of sliced ham stored at 4 degrees C and 12 degrees C, due to
recontamination in the cutting room. On the contrary, the progressive
deterioration of whole ham under the same storage conditions was associated with
a non-identifiable group of leuconostoc-like bacteria. Except for lactic acid
bacteria, no other organism grew in vacuum packs of either sliced or whole ham.
Although atypical leuconostocs could not be detected among isolates recovered
from freshly produced whole ham, they appeared to survive cooking and proliferate
during storage. Neither these organisms however, nor Lact. sake and Leuc.
mesenteroides were important in curing and tumbling as carnobacteria, mainly
Carnobacterium divergens, and Brochothrix thermosphacta dominated at this stage.
A progressive inversion of the ham microflora from mostly Gram-negative at the
beginning of processing to highly Gram-positive prior to cooking was noted.
Listeria monocytogenes cross-contaminated ham during tumbling. However, the
pathogen was always absent from the vacuum-packed product provided that heating
to a core temperature of 70 degrees C occurred and recontamination during slicing
and packing was prevented. The percentage distribution of different species of
lactic acid bacteria as well as the uncommon phenotypic characteristics of some
strains were discussed.
PMID- 9633663
TI - Specific assays for bacteria using phage mediated release of adenylate kinase.
AB - A sensitive and rapid assay method for the specific detection of bacteria was
developed using Escherichia coli and Salmonella newport as the test organisms.
Bacteriophages were used to provide specific lysis of the bacteria and then the
release of cell contents was measured by ATP bioluminescence. Increased
sensitivity was obtained by focusing on the bacteria's adenylate kinase (AK) as
the cell marker instead of ATP as conventionally used. Fewer than 10(3) E. coli
cells could be readily detected in less than 1 h. Salmonella newport assays,
although as sensitive, were slower and took up to 2 h. The effects of the culture
medium, the phage, and the presence of non-specific bacteria were examined.
PMID- 9633664
TI - Airborne movement of anthrax spores from carcass sites in the Etosha National
Park, Namibia.
AB - Tests for airborne movement of anthrax spores downwind from three heavily
contaminated carcass sites were carried out under a range of wind conditions.
Anthrax spores were detected in just three of 43 cyclone or gelatin filter air
samples taken at distances of 6, 12 and 18 m from the sites. In addition, nine
positives resulted during sampling sessions in which the site was mechanically
disturbed, with a further five positives being found in sessions subsequent to
those in which the site had been disturbed. The three positive samples not
related to man-made disturbance were associated with the highest winds
experienced during the study. Despite colony counts exceeding 100 on the culture
plates in three instances, calculations showed that these represented very low
worst case probable spore inhalation rates for animals or humans exposed to such
levels. The low number of positives, the clear pattern of rapidly declining
numbers of anthrax spores with distance downwind from the centres of the sites
apparent on settle plates, and the persisting levels of contamination despite
wind and rain, collectively suggest that the anthrax spores were associated with
fairly heavy particles, although this was not seen by electron microscopy on soil
samples from the sites. Overall, the findings are interpreted as indicating that
it is very unlikely that Etosha animals contract anthrax by the inhalation route
while simply in transit near or across a carcass site. The significance of the
observations in relation to weather conditions in the Etosha, other studies on
particulate aerosols in the region, and reports of long-distance airborne
movement of microbes, is discussed.
PMID- 9633665
TI - Heat shock and thermotolerance of Escherichia coli O157:H7 in a model beef gravy
system and ground beef.
AB - Duplicate beef gravy or ground beef samples inoculated with a suspension of a
four-strain cocktail of Escherichia coli O157:H7 were subjected to sublethal
heating at 46 degrees C for 15-30 min, and then heated to a final internal
temperature of 60 degrees C. Survivor curves were fitted using a linear model
that incorporated a lag period (TL), and D-values and 'time to a 4D inactivation'
(T4D) were calculated. Heat-shocking allowed the organism to survive longer than
non-heat-shocked cells; the T4D values at 60 degrees C increased 1.56- and 1.50
fold in beef gravy and ground beef, respectively. In ground beef stored at 4
degrees C, thermotolerance was lost after storage for 14 h. However, heat-shocked
cells appeared to maintain their thermotolerance for at least 24 h in ground beef
held to 15 or 28 degrees C. A 25 min heat shock at 46 degrees C in beef gravy
resulted in an increase in the levels of two proteins with apparent molecular
masses of 60 and 69 kDa. These two proteins were shown to be immunologically
related to GroEL and DnaK, respectively. Increased heat resistance due to heat
shock must be considered while designing thermal processes to assure the
microbiological safety of thermally processed foods.
PMID- 9633666
TI - The structure of psychosis: latent class analysis of probands from the Roscommon
Family Study.
AB - BACKGROUND: The nosologic structure of psychotic illness, still influenced as
much by historical as empirical perspectives, remains controversial. METHODS:
Latent class analysis was applied to detailed symptomatic and outcome assessments
of probands (n=343) with broadly defined schizophrenia and affective illness
ascertained from a population-based psychiatric registry in Roscommon County,
Ireland. First-degree relatives (n=942) were assessed by personal interview
and/or review of hospital record. RESULTS: Six classes were found, all of which
bore substantial resemblance to current or historical nosologic constructs. In
order of decreasing frequency, they were (1) classic schizophrenia, (2) major
depression, (3) schizophreniform disorder, (4) bipolar-schizomania, (5)
schizodepression, and (6) hebephrenia. These classes differed on many historical
and clinical variables not used in the latent class analysis. Compared with
relatives of controls, significantly increased rates of major depression were
seen in relatives of depressed and schizodepressed probands. Significantly
increased rates of bipolar illness were restricted to relatives of bipolar
schizomanic probands. The risks for schizophrenia and schizophrenia spectrum
disorders were significantly increased in relatives of all proband classes except
major depression. This increase was moderate for bipolar-schizomanic probands,
substantial for schizophrenic, schizophreniform, and schizodepressed probands,
and marked for hebephrenic probands. CONCLUSIONS: These results suggest a
relatively complex typology of psychotic syndromes consistent neither with a
unitary model nor with a Kraepelinian dichotomy. The familial vulnerability to
psychosis extends across several syndromes, being most pronounced in those with
schizophrenialike symptoms. The familial vulnerability to depressive and manic
affective illness is somewhat more specific.
PMID- 9633667
TI - From Kraepelin to Kretschmer leavened by Schneider: thextransition from
categories of psychosis to dimensions of variation intrinsic to homo sapiens.
PMID- 9633668
TI - The structure of psychosis: syndromes and dimensions.
PMID- 9633669
TI - Sympathetic activity in patients with panic disorder at rest, under laboratory
mental stress, and during panic attacks.
AB - BACKGROUND: The sympathetic nervous system has long been believed to be involved
in the pathogenesis of panic disorder, but studies to date, most using peripheral
venous catecholamine measurements, have yielded conflicting and equivocal
results. We tested sympathetic nervous function in patients with panic disorder
by using more sensitive methods. METHODS: Sympathetic nervous and adrenal
medullary function was measured by using direct nerve recording (clinical
microneurography) and whole-body and cardiac catecholamine kinetics in 13
patients with panic disorder as defined by the DSM-IV, and 14 healthy control
subjects. Measurements were made at rest, during laboratory stress (forced mental
arithmetic), and, for 4 patients, during panic attacks occurring spontaneously in
the laboratory setting. RESULTS: Muscle sympathetic activity, arterial plasma
concentration of norepinephrine, and the total and cardiac norepinephrine
spillover rates to plasma were similar in patients and control subjects at rest,
as was whole-body epinephrine secretion. Epinephrine spillover from the heart was
elevated in patients with panic disorder (P=.01). Responses to laboratory mental
stress were almost identical in patient and control groups. During panic attacks,
there were marked increases in epinephrine secretion and large increases in the
sympathetic activity in muscle in 2 patients but smaller changes in the total
norepinephrine spillover to plasma. CONCLUSIONS: Whole-body and regional
sympathetic nervous activity are not elevated at rest in patients with panic
disorder. Epinephrine is released from the heart at rest in patients with panic
disorder, possibly due to loading of cardiac neuronal stores by uptake from
plasma during surges of epinephrine secretion in panic attacks. Contrary to
popular belief, the sympathetic nervous system is not globally activated during
panic attacks.
PMID- 9633670
TI - Catecholamines and pathogenesis in panic disorder.
PMID- 9633671
TI - Effects of tryptophan depletion vs catecholamine depletion in patients with
seasonal affective disorder in remission with light therapy.
AB - BACKGROUND: Although hypotheses about the therapeutic mechanism of action of
light therapy have focused on serotonergic mechanisms, the potential role, if
any, of catecholaminergic pathways has not been fully explored. METHODS: Sixteen
patients with seasonal affective disorder who had responded to a standard regimen
of daily 10000-lux light therapy were enrolled in a double-blind, placebo
controlled, randomized crossover study. We compared the effects of tryptophan
depletion with catecholamine depletion and sham depletion. Ingestion of a
tryptophan-free amino acid beverage plus amino acid capsules was used to deplete
tryptophan. Administration of the tyrosine hydroxylase inhibitor alpha-methyl
paratyrosine was used to deplete catecholamines. Diphenhydramine hydrochloride
was used as an active placebo during sham depletion. The effects of these
interventions were evaluated with measures of depression, plasma tryptophan
levels, and plasma catecholamine metabolites. RESULTS: Tryptophan depletion
significantly decreased plasma total and free tryptophan levels. Catecholamine
depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol
and homovanillic acid levels. Both tryptophan depletion and catecholamine
depletion, compared with sham depletion, induced a robust increase (P<.001,
repeated-measures analysis of variance) in depressive symptoms as measured with
the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version.
CONCLUSIONS: The beneficial effects of light therapy in the treatment of seasonal
affective disorder are reversed by both tryptophan depletion and catecholamine
depletion. These findings confirm previous work showing that serotonin plays an
important role in the mechanism of action of light therapy and provide new
evidence that brain catecholaminergic systems may also be involved.
PMID- 9633672
TI - Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with
remitted depression on serotonin reuptake inhibitors.
AB - BACKGROUND: In previous studies, depletion of brain serotonin by administration
of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the
antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in
euthymic patients who had a history of major depression, and (2) enhanced rapid
eye movement (REM) sleep in normal volunteers. In this study, we hypothesized
that the TFD would not only increase depressive symptoms but also the propensity
for REM sleep in euthymic patients treated with SSRIs. METHODS: Ten fully
remitted, medicated male patients who had a history of major depressive episode
ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the
control drink) in double-blind, random order on separate days. The effects were
assessed with mood ratings, plasma tryptophan concentrations, and an all-night
sleep electroencephalogram. RESULTS: The TFDs produced a dose-dependent reduction
in plasma tryptophan concentrations, sleep latency, and REM latency, as well as
increased REM percentage, REM minutes, REM density, and total sleep time. Neither
strength of TFD altered mood to a clinically significant degree. CONCLUSIONS:
Although the TFD affected plasma tryptophan concentrations and various sleep
measures, our study did not confirm previous reports that TFD temporarily
reversed the antidepressant effects of SSRIs in euthymic patients. Our patients,
however, had been treated for a longer period with SSRIs and were more fully
remitted at the time of the study. Our results suggest that TFD-induced relapse
in SSRI-treated patients in remission decreases as a function of treatment
duration, degree of remission, or both.
PMID- 9633673
TI - Cerebral gray matter volume deficits in first episode psychosis.
AB - BACKGROUND: Structural brain differences including decreased gray matter and
increased cerebrospinal fluid volumes have been observed in the brains of
chronically ill patients with schizophrenia. We hypothesized that deficits in
gray matter volume would be present in patients presenting with a first episode
of nonaffective psychosis. METHODS: We used magnetic resonance imaging to compare
the brains of 77 patients assessed as having a first episode of psychosis
(meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder,
schizoaffective disorder, delusional disorder, or psychotic disorder not
otherwise specified) with those of 61 healthy controls matched for age, sex,
race, and parental socioeconomic status. Axial, dual-echo scans of the whole
brain were segmented into gray matter, white matter, and cerebrospinal fluid
compartments using a computerized volumetric approach. These measures were
corrected for the significant effects of intracranial volume and age prior to
performing between-group comparisons. RESULTS: The first episode psychosis group
had significantly smaller gray matter volume (t[136] = -2.2; P = .03) and greater
cerebrospinal fluid volume (t[136] = 2.5; P = .02) than normal controls. In the
patient group, gray matter volumes were positively correlated with estimates of
IQ but not with age of onset, duration of illness, or measures of premorbid
functioning. CONCLUSIONS: Deficits in gray matter volume are present in patients
experiencing first episode nonaffective psychosis. The magnitude of these
differences is smaller than has been described in more chronically ill patients.
PMID- 9633674
TI - Expressed emotion and psychiatric relapse: a meta-analysis.
AB - BACKGROUND: Expressed emotion (EE) is a measure of the family environment that
has been demonstrated to be a reliable psychosocial predictor of relapse in
schizophrenia. However, in recent years some prominent nonreplications of the EE
relapse relationship have been published. To more fully address the question of
the predictive validity of EE, we conducted a meta-analysis of all available EE
and outcome studies in schizophrenia. We also examined the predictive validity of
the EE construct for mood disorders and eating disorders. METHODS: An extensive
literature search revealed 27 studies of the EE-outcome relationship in
schizophrenia. Using meta-analytic procedures, we combined the findings of these
investigations to provide an estimate of the effect size associated with the EE
relapse relationship. We also used meta-analysis to provide estimates of the
effect sizes associated with EE for mood and eating disorders. RESULTS: The
results confirmed that EE is a significant and robust predictor of relapse in
schizophrenia. Additional analyses demonstrated that the EE-relapse relationship
was strongest for patients with more chronic schizophrenic illness.
Interestingly, although the EE construct is most closely associated with research
in schizophrenia, the mean effect sizes for EE for both mood disorders and eating
disorders were significantly higher than the mean effect size for schizophrenia.
CONCLUSION: These findings highlight the importance of EE in the understanding
and prevention of relapse in a broad range of psychopathological conditions.
PMID- 9633675
TI - A prospective study of heart rate response following trauma and the subsequent
development of posttraumatic stress disorder.
AB - BACKGROUND: Physiological arousal during traumatic events may trigger the
neurobiological processes that lead to posttraumatic stress disorder (PTSD). This
study prospectively examined the relationship between heart rate and blood
pressure recorded immediately following a traumatic event and the subsequent
development of PTSD. METHODS: Eighty-six trauma survivors who presented at the
emergency department of a general hospital were followed up for 4 months. Heart
rate and blood pressure were recorded on arrival at the emergency department.
Heart rate, anxiety, depression, and PTSD symptoms were assessed 1 week, 1 month,
and 4 months later. The clinician-administered PTSD scale defined PTSD status at
4 months. RESULTS: twenty subjects (23%) met PTSD diagnostic criteria at the 4
month assessment (PTSD group), and 66 (77%) did not (non-PTSD group). Subjects
who developed PTSD had higher heart rates at the emergency department (95.5+/
13.9 vs 83.3+/-10.9 beats per minute, t=4.4, P<.001) and 1 week later (77.8+/
11.9 vs 72.0+/-9.5 beats per minute, t=2.25, P<.03), but not after 1 and 4
months. The groups did not differ in initial blood pressure measurement. Repeated
measures analysis of variance (ANOVA) for heart rate showed a significant group
effect (P<.02), time effect (P<.001), and group x time interaction (P<.001). The
time effect and group x time interaction remained significant when adjusted for
sex, age, trauma severity, immediate response, and dissociation during the
traumatic event. CONCLUSION: Elevated heart rate shortly after trauma is
associated with the later development of PTSD.
PMID- 9633676
TI - Psychotherapy and managed care.
PMID- 9633677
TI - The role of psychotherapy: psychiatry's resistance to managed care.
PMID- 9633678
TI - Current and emerging drug therapies in the management of Parkinson's disease.
PMID- 9633679
TI - History of levodopa and dopamine agonists in Parkinson's disease treatment.
AB - Striatal dopamine deficiency in Parkinson's disease (PD), first described in
1960, was a key event that led to the era of levodopa therapy. In 1961, levodopa
was first tried in PD patients, but throughout most of the 1960s the results were
inconsistent. In 1967, questions about the effectiveness of levodopa in PD were
finally set aside when Cotzias and colleagues reported dramatic improvement in PD
patients with oral administration of levodopa in increasing amounts over long
periods. The major side effects of levodopa administration, i.e., dyskinesias and
motor fluctuations, also became apparent at this time. In the early 1970s, the
advantages of adding a dopa decarboxylase inhibitor to treatment were discovered-
reducing side effects and gaining better symptom control--and the first levodopa
combination, carbidopa/levodopa, became commercially available in 1975. Since
then, PD researchers have attempted to overcome complications with such
techniques as continuous levodopa infusion and, most recently, long-acting
levodopa combinations. A dopamine agonist, apomorphine, was used in 1970 as a
means to overcome side effects and loss of levodopa efficacy. However, side
effects and difficulty of administration limited its use. Dopamine agonists began
to find a place in routine treatment of PD after the discovery of bromocriptine's
benefits in PD in 1974. Since then, new approaches have been tried, such as
dopamine agonist monotherapy and early therapy in combination with levodopa. The
development of new dopamine agonists has led to characterization of dopamine
receptor subtypes and agonists targeted to stimulation of specific receptors.
PMID- 9633680
TI - Mechanism of action of dopaminergic agents in Parkinson's disease.
AB - As the substantia nigra degenerates in Parkinson's disease (PD), the
nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD
symptoms. Although dopamine does not readily cross the blood-brain barrier, its
precursor, levodopa, does. Levodopa is absorbed in the small bowel and is rapidly
catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O
methyltransferase (COMT). Because gastric AADC and COMT degrade levodopa, the
drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors
of COMT will also enter clinical use. Although the exact site of decarboxylation
of exogenous levodopa to dopamine in the brain is unknown, most striatal AADC is
located in nigrostriatal dopaminergic nerve terminals. Newly synthesized dopamine
is stored in the terminals and then released, stimulating postsynaptic dopamine
receptors and mediating the antiparkinsonian action of levodopa. Dopamine
agonists act directly on postsynaptic dopamine receptors, thus obviating the need
for metabolic conversion, storage, and release. How the actions of dopaminergic
drugs produce side effects and how these side effects should be managed are
discussed.
PMID- 9633681
TI - Implications of the 5-year CR FIRST trial. Sinemet CR Five-Year International
Response Fluctuation Study.
AB - Almost since the introduction of levodopa for Parkinson's disease (PD), its side
effects have concerned clinicians. One strategy to avoid side effects has been to
delay levodopa therapy; an alternative has been to use early therapy but to avoid
fluctuations in plasma levodopa levels. This latter strategy led to the
development of sustained-release carbidopa-levodopa, which was compared with
immediate-release carbidopa-levodopa in the CR Five-Year International Response
Fluctuation Study (FIRST), a 5-year multicenter study of early, levodopa-naive PD
patients. The incidence of motor fluctuations was lower than expected for both
groups, and patients receiving sustained-release carbidopa-levodopa fared better
on the activities of daily living portion of the Unified Parkinson's Disease
Rating Scale and on portions of the Nottingham Health Profile. The trial
demonstrated the value of low-dose therapy, the lack of toxicity of this low-dose
approach over 5 years in early PD.
PMID- 9633682
TI - Initiating therapy for Parkinson's disease.
AB - Accurate diagnosis and individualized assessment of the risks and benefits of
available antiparkinsonian medications should guide initiation of treatment for
patients with early Parkinson's disease (PD). In general, the goals of treatment
for younger patients (less than age 60 years) are control of impairing symptoms,
sparing of levodopa to minimize long-term complications, and consideration of
neuroprotection. The primary initial medication choices for patients under age 50
years include selegiline, amantadine, and anticholinergic agents. Patients in
their fifties may require a dopamine agonist in addition to or instead of
selegiline to achieve adequate symptom control. If the desired response is still
not achieved, sustained-release carbidopa-levodopa should be added, followed by
adjunctive amantadine or anticholinergic therapy. For older patients (60 years
and over), improvement of functional impairment is the primary goal. For these
patients, a special concern is to avoid inducing or exacerbating cognitive
impairment. Sustained-release carbidopa-levodopa is considered first-line
treatment for these patients. Inadequate response can be handled by a trial of
immediate-release carbidopa-levodopa and then addition of a dopamine agonist when
maximum levodopa doses are reached. Anticholinergic agents, amantadine, and
selegiline should be avoided because of their CNS effects.
PMID- 9633683
TI - Adjuncts to levodopa therapy: dopamine agonists.
AB - The classical role of dopamine agonists in Parkinson's disease (PD) therapy is
adjunctive treatment to levodopa once "wearing-off" fluctuations or more
malignant types of "on-off" swings have developed. Dopamine agonists reduce the
frequency, severity, and duration of "off" periods while allowing the levodopa
dose to be reduced. Interest is growing in the role of dopamine agonists as
primary monotherapy in PD. Studies of early monotherapy have shown that, even
with sustained treatment, drug-induced dyskinesias rarely develop. However, this
approach is successful for more than 3 years in only about 30% of all PD
patients. Continuous dopaminergic stimulation via subcutaneous dopamine agonist
infusions is being investigated as a way to control levodopa-associated peak-dose
dyskinesias. Early combined treatment with levodopa has been suggested as
effective while avoiding long-term complications, but the therapy remains
controversial. Despite the entry of several new dopamine agonists into clinical
practice, the ideal agonist, with long duration of action and efficacy equal to
that of levodopa, is still lacking. The clinical pharmacology of dopamine
agonists is reviewed.
PMID- 9633684
TI - Extending levodopa action: COMT inhibition.
AB - Degradation of levodopa in the periphery is known to be associated with motor
fluctuations and dyskinesia in Parkinson's disease (PD) patients. The enzyme
catechol-O-methyltransferase (COMT) is responsible for much of this degradation.
Therefore, inhibiting COMT activity is one method of extending the action of
levodopa. The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and
tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity
centrally. COMT inhibitors increase patients' duration of response to levodopa
and reduce response fluctuations. Administration may prolong levodopa-induced
dyskinesia, but peak-dose dyskinesia does not appear to increase. To reduce
dyskinesia, the total daily dose of levodopa can be reduced.
PMID- 9633685
TI - Managing the neuropsychiatric symptoms of Parkinson's disease.
AB - Neuropsychiatric symptoms frequently complicate the treatment of Parkinson's
disease (PD). Approximately 27% of PD patients are demented, and approximately
19% are cognitively impaired without being demented. These 46% of patients are
prone to development of delirium when they take antiparkinsonian drugs.
Approximately 40% of PD patients are depressed. The depression may be endogenous
or exogenous, apathetic or agitated. Approximately 40% of PD patients are anxious
or have panic attacks. The attacks may or may not be associated with depression.
This article reviews the diagnosis of these symptoms and discusses their
management.
PMID- 9633686
TI - Levodopa neurotoxicity: experimental studies versus clinical relevance.
AB - Levodopa therapy remains the major form of treatment for the symptoms of
Parkinson's disease (PD). However, there has been a suspicion that its use may
hasten the progression of nigral cell degeneration. This concept is based on the
ability of levodopa to generate reactive oxygen species and the apparent
involvement of oxidative stress as a component of the degenerative process that
occurs in PD. Indeed, in vitro autoxidation of levodopa causes oxidative stress,
leading to neuronal destruction by necrosis or apoptosis. However, its chronic
administration to normal rats or primates has not been associated with clear
evidence for destruction of the nigrostriatal pathway. In contrast, in situations
in which the nigrostriatal tract is already damaged, there is some evidence to
suggest that levodopa treatment can produce further cell destruction associated
with oxidative processes. However, levodopa does not appear to be toxic to the
development of fetal nigral neurons or to the survival of fetal cell transplants.
There is no clinical evidence to suggest that levodopa has adverse effects on
dopamine cells in normal humans or on the viability of remaining dopaminergic
cells in patients with PD. However, it is only now that specific clinical trials
designed to examine the potential neurotoxicity of levodopa are being undertaken.
PMID- 9633687
TI - Intravenous diphenylhydantoin in treatment of acute repetitive seizures. 1968.
PMID- 9633688
TI - Genotypes, phenotypes, and frontotemporal dementia: take your pick.
PMID- 9633689
TI - The use and cost of medical resources: what will we pay for neurologic health?
PMID- 9633690
TI - Tourette's syndrome and 'PANDAS': will the relation bear out? Pediatric
autoimmune neuropsychiatric disorders associated with streptococcal infection.
AB - Despite strong evidence of the importance of hereditary factors in the etiology
of Tourette's syndrome (TS), research findings have consistently pointed to a
role of environmental influences. A recent line of research has suggested that
tic disorders and associated behavioral disturbances, such as obsessive
compulsive disorder, might develop following streptococcal infection by the
process of molecular mimicry, whereby antibodies directed against bacterial
antigens cross-react with brain targets. Such investigations have given rise to
the notion that there is a spectrum of childhood neurobehavioral disorders
(termed pediatric autoimmune neuropsychiatric disorders associated with
streptococcal infection [PANDAS]) that arise by postinfectious autoimmune
mechanisms. This article reviews research results supporting the concept of
PANDAS and discusses their limitations. Well-designed and adequately controlled
studies are needed to determine whether there is a true etiologic relation
between streptococcal infection and the onset or exacerbation of childhood
neuropsychiatric disorders and whether the use of immune-modifying therapies for
these conditions is rational.
PMID- 9633691
TI - The behavioral neurology of cerebral white matter.
AB - Behavioral neurology has primarily focused on brain-behavior relations as
revealed by disorders of the cerebral cortex and subcortical gray matter.
Disorders of cerebral white matter have received less attention. This article
considers the contribution of cerebral white matter to normal behavioral function
and the effects of white matter disorders on behavior. Diffuse dysfunction is
more common than focal impairment, and the term white matter dementia has been
proposed as a clinical entity. Conventional neuroimaging has enabled more
accurate identification of white matter regions participating in neurobehavioral
operations, and newer imaging techniques may define white matter connectivity
within and between the hemispheres. As an essential component of neural networks,
cerebral white matter contributes to cognitive and emotional functions, and
lesions of white matter disconnect these networks to produce neurobehavioral
syndromes.
PMID- 9633692
TI - Familial aggregation in frontotemporal dementia.
AB - OBJECTIVE AND BACKGROUND: Frontotemporal dementia (FTD) is a common, non
Alzheimer's dementia. Its familial occurrence has been reported, but the
frequency of positive family history is unknown. METHODS: We carried out a
nationwide genetic-epidemiologic study of FTD in the Dutch population of 15
million people. The family history of dementia was analyzed in 74 FTD patients
and 561 age- and gender-matched control subjects. RESULTS: We found one or more
first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD
patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD
patients had two or more first-degree relatives with dementia compared with 0.9%
of the control subjects. Seven percent of FTD patients showed the ApoE4E4
genotype versus 2.3% of the control subjects. The first-degree relatives of FTD
had a risk of 22% for dementia before age 80 compared with 11% in relatives of
control subjects. The age of onset of dementia in affected first-degree relatives
of FTD patients (60.9+/-10.6 years) was significantly lower than among affected
relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of
FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing
dementia before age 80 than relatives of control subjects. The hazard ratio in
the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7).
CONCLUSION: This study documents the importance of genetic factors in a
proportion of FTD patients with the age at onset of dementia in first-degree
relatives being 11 years earlier than in the general population.
PMID- 9633693
TI - Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to
17q21-22.
AB - OBJECTIVE: The clinical and pathologic features of hereditary dysphasic
disinhibition dementia (HDDD) are described to determine whether it is a variant
of known dementias. BACKGROUND: Several dementing disorders have clinical and
pathologic similarities with AD, Pick's disease, and the "nonspecific" dementias.
A detailed description of clinical and pathologic presentation will aid
classification, but ultimately the discovery of causative gene(s) will define
these disorders. METHODS: The authors performed a clinical assessment: gross and
microscopic pathologic evaluation of brain tissue, genetic linkage studies, and
sequence analyses. RESULTS: HDDD is an autosomal-dominant frontotemporal dementia
with many similarities to Pick's disease. Salient clinical features are global
dementia with disproportionate dysphasia and "frontotemporal" symptoms. A linkage
between HDDD and 17q21-22 was shown, with a maximum lod score of 3.68 at zero
recombination. CONCLUSIONS: Several dementias have been linked to the same region
and have been termed frontotemporal dementia with parkinsonism linked to
chromosome 17. These disorders may represent phenotypic variants arising from
mutations within a common gene.
PMID- 9633694
TI - Association of CYP2D microsatellite polymorphism with Lewy body variant of
Alzheimer's disease.
AB - OBJECTIVE: To examine the genetic association of CYP2D6 locus with Lewy body
variant (LBV) and Parkinson's disease (PD). METHODS: Allelic association was
studied in patients with pure AD, LBV, and PD by using the CYP2D microsatellite,
the (dG-dT)n dinucleotide repeat (n=16 to 27) located between CYP2D8P and CYP2D7
genes, and the CYP2D6 B and D mutations. RESULTS: We found overrepresentation of
the alleles longer than 21 repeat (the long-type alleles) in LBV (allele
frequency, 0.313) (odds ratio=1.99, p=0.019 by chi2 test) and in PD (0.298) (odds
ratio=1.86, p=0.037), but not in pure AD (0.196), compared with the age-matched
control (0.186). Strong association was noted of the long-type alleles with the
CYP2D6 B mutation (odds ratio=88.50, p < 0.001 by Fisher's exact test), but not
with the D mutation or the deletion of CYP2D6 gene. CONCLUSIONS: The CYP2D locus
is closely associated with LBV and PD. The CYP2D6 B mutation may be involved in
pathogenesis of LBV and PD in a dominant-negative manner, or in the linkage
disequilibrium of the CYP2D microsatellite to another pathogenic gene locus.
PMID- 9633695
TI - Preclinical prediction of Alzheimer's disease using SPECT.
AB - BACKGROUND: Regional cerebral perfusion measured by single photon emission
computed tomography (SPECT) was examined as a preclinical predictor of the
development of Alzheimer's disease (AD). METHODS: Singular value decomposition
was used to produce 20 SPECT factors (known as vectors) (n=152). Vector scores
were then computed for four groups (n=136), differing in cognitive status: Group
1--normal controls at both baseline and follow-up; Group 2--subjects with
"questionable" AD at both baseline and follow-up; Group 3--subjects with
questionable AD at baseline who converted to AD on follow-up (Converters); Group
4--subjects with AD at baseline. All SPECT data in the analyses were gathered at
baseline. RESULTS: The four groups could be distinguished on the basis of their
baseline SPECT data (p < or = 0.00005; hit rate=83%). Regional decreases in
perfusion were most prominent among Converters in the hippocampal-amygdaloid
complex, the posterior cingulate, the anterior thalamus, and the anterior
cingulate. Inclusion of apolipoprotein E status did not significantly improve the
discrimination. CONCLUSIONS: SPECT data gathered and analyzed in this manner may
be useful as one aspect of the preclinical prediction of AD. Three of the four
brain regions important for discriminating Converters from normal controls
involve a distributed brain network pertaining to memory, suggesting that this
network may be selectively affected in the earliest stages of AD.
PMID- 9633696
TI - Incidence and subtypes of dementia in southern Taiwan: impact of socio
demographic factors.
AB - OBJECTIVE: To determine the incidence rate (IR) and subtypes of dementia in
southern Taiwan. METHODS: From a cohort of 2,915 community inhabitants aged 65
years and over, 2,507 and 2,175 subjects participated in the first- and second
year follow-up surveys, respectively. A two-phase study used the Mini-Mental
State Examination in phase I and the Consortium to Establish a Registry of
Alzheimer's Disease (CERAD) neuropsychological battery and the neurobehavioral
examination in phase II. We applied International Classification of Diseases
(ICD)-10NA criteria for dementia, National Institute of Neurological and
Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders
Association (NINCDS-ADRDA) guidelines for Alzheimer's disease (AD), and National
Institute of Neurological Disorders and Stroke-Association Internationale pour la
Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular
dementia (VaD). RESULTS: The annual IR for total dementia was 1.28%, which
increased with age from 0.77% for 65- to 74-year-olds to 6.19% for persons aged
85 years or older. AD (25 cases, 41.7%, IR=0.54%) was the most common cause of
dementia, followed by VaD (19 cases, 31.7%, IR=0.41%) and mixed dementia (9
cases, 15.0%). After adjusting for sex, increasing age was significantly
associated with total dementia and AD (p < 0.01). Illiteracy was associated with
a marginally increased risk for total dementia (aRR=1.59, p < 0.1) as was being
female for AD (aRR = 1.92, p < 0.1). The 2-year mortality rate was high among the
demented (48% in total dementia, 38% in AD, and 60% in VaD). CONCLUSIONS: The age
specific incidence of dementia in Taiwan is approaching that of developed
countries and the low prevalence of dementia (especially VaD) may be mainly due
to the high mortality. Age was the major risk factor for total dementia and AD.
Being female was probably a risk factor for AD, as was illiteracy for total
dementia.
PMID- 9633697
TI - Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male
twins.
AB - OBJECTIVE: To investigate the combined effect of the apolipoprotein E epsilon4
(ApoE*4) allele and midlife cardiovascular risk factors on cognitive decline.
METHODS: Data are from the National Heart, Lung, and Blood Institute Twin Study-a
longitudinal cardiovascular epidemiologic study of World War II male veteran
twins currently in its 27th year of follow-up. Subjects were assessed for
cardiovascular risk factors, including BP and glucose levels, at mean ages 48,
58, and 63 years. Participants in the current study are 410 individual twin
subjects for whom cognitive function was measured twice, at ages 63 and 73 years.
Ten-year change scores in performance on neuropsychological test examinations
were adjusted for age, education, baseline score, and incident cardiovascular
disease. RESULTS: For the sample as a whole, we observed a significant decline (p
< 0.01) in cognitive performance over the 10 years of follow-up. ApoE*4 carriers
with midlife hyperglycemia experienced the greatest decline in performance, which
was also greater than expected from the separate effects combined. Midlife
hypertension and ApoE*4, were each associated with excess decline in performance
on tests of psychomotor speed. Their joint effect, however, was not greater than
expected from the separate effects combined. CONCLUSIONS: ApoE*4 and midlife
cardiovascular risk factors may have a synergistic effect on decline in cognitive
function. This effect may be due to greater vascular or degenerative damage among
subjects with ApoE*4.
PMID- 9633698
TI - Regional glucose metabolic abnormalities are not the result of atrophy in
Alzheimer's disease.
AB - OBJECTIVE: To determine whether the hypometabolism observed in PET images of
patients with Alzheimer's disease (AD) is due entirely to brain atrophy.
BACKGROUND: Reduced brain glucose metabolism in AD patients measured using PET
has been reported by numerous authors. Actual glucose metabolic values in AD may
be reduced artificially because of brain atrophy, which accentuates the partial
volume effect (PVE) on data collected by PET. METHODS: Using segmented MR images,
we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate
the effect of atrophy on uncorrected values for brain metabolism in AD patients
and healthy control subjects. RESULTS: Global glucose metabolism was reduced
significantly before and after correction in AD patients compared with controls.
Before PVE correction, glucose metabolic values in patients were lower than in
control subjects in the inferior parietal, frontal, and lateral temporal cortex;
in the posterior cingulate; and in the precuneus. These reductions remained
significantly lower after PVE correction, although in the posterior cingulate the
difference in metabolism between AD patients and control subjects lessened.
Regional glucose metabolism of these areas with PVE correction was lower in
moderately-severely demented patients than in mildly demented patients.
CONCLUSION: Reduced glucose metabolism measured by PET in AD is not simply an
artifact due to an increase in CSF space induced by atrophy, but reflects a true
metabolic reduction per gram of tissue.
PMID- 9633699
TI - Health care utilization in multiple sclerosis: a population-based study in
Olmsted County, MN.
AB - OBJECTIVE: The authors sought to determine acute ambulatory- and hospital-billed
charges for the Olmsted County, Minnesota Multiple Sclerosis (MS) Disability
Prevalence Cohort and compare them to those incurred by the general population.
METHODS: Billed charges for 155 people with clinically definite or laboratory
supported MS were compared with those of age- and gender-matched non-MS controls.
Billing data, including all inpatient and outpatient acute and rehabilitative
medical care charges over a 5-year period surrounding a December 1, 1991
prevalence date, were analyzed. Data were correlated with level of disability
using the Minimal Record of Disability for MS. RESULTS: Median total annual
billed charges for most individuals with MS, including those with less severe
($1,277) and relapsing-remitting illness ($1,348), did not differ from those for
controls ($1,327, p=0.075). Only those with severe MS (22.6%) had median annual
medical charges higher than controls ($5,440, p < 0.001). Male patients with MS
had higher median annual total charges ($2,353) than male controls ($762,
p=0.003). Total charges for female patients with MS ($1,440) were not different
from those for female controls ($1469). Median annual outpatient charges were 15%
more for the MS group ($1,418) than for controls ($1,231). Patients with MS had a
mean of 0.2 hospital admissions annually compared with 0.1 annual admissions per
control patient. Among variables collected on persons with MS, the Expanded
Disability Status Scale was the strongest predictor of level of charges (p <
0.001). CONCLUSION: Acute ambulatory- and hospital-billed charges for most
patients with MS do not differ from those of the general population.
PMID- 9633700
TI - Relation between MR abnormalities and patterns of cognitive impairment in
multiple sclerosis.
AB - OBJECTIVE: This study correlated the extent of abnormalities detected by
different magnetic resonance imaging (MRI) techniques [proton density (PD)
weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall
cognitive, frontal lobe, and memory impairments in patients with MS. PATIENTS:
There were 30 clinically definite MS patients, with different disease courses.
EXCLUSION CRITERIA: psychoactive/steroid treatments, mood disorders, acute
relapse phase. MAIN OUTCOME MEASURES: Neuropsychological test results. Total
(TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22
patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and
analysis of the MTR histograms from brain tissue axial slabs on MTI scans.
RESULTS: Patients with frontal lobe deficits (n=15) or memory impairment (n-17)
had a higher TLL on PD scans (p=0.04 and p=0.01, respectively). Patients with
frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03)
scans. No significant relationships between the extent of T1-weighted lesion
loads and the presence of any neuropsychological impairment. Mean MTR of both MS
lesions and whole brain tissue was lower in patients with frontal lobe impairment
(p=0.04). MRI lesion loads correlated significantly with some neuropsychological
test scores. CONCLUSIONS: Lesion loads on PD-weighted MRI and MTI-derived
measures are associated with cognitive decline in MS patients. Overall
macroscopic and microscopic brain damage is more important than the corresponding
regional brain disease in determining deficits of selective cognitive domains.
PMID- 9633701
TI - Correlation of volumetric magnetization transfer imaging with clinical data in
MS.
AB - We examined the relations between quantitative volumetric estimates of cerebral
lesion load based on magnetization transfer imaging (MTI), clinical data, and
measures of neuropsychological function in 44 patients with clinically diagnosed
MS. In this population we assessed the correlation between several volumetric MTI
measures, measures of neurologic function (Kurtzke Expanded Disability Status
Scale and Ambulation Index), and disease duration using Spearman's correlation
coefficient. Patients were classified on the basis of neuropsychological test
performance as severely impaired, moderately impaired, and normal. We assessed
differences between these groups with respect to MTI results using the Kruskal
Wallis test. MTI measures corrected for brain volume were found to correlate with
disease duration (p < 0.01) and showed suggestive correlations with measures of
neurologic impairment (p < 0.05). Individual neuropsychological tests correlated
with MTI measures corrected and not corrected for brain volume (p < 0.001). An
MTI measure not corrected for brain volume differed (p < 0.05) between severely
impaired, moderately impaired, and normal patients. These preliminary results
suggest that volumetric MTI analysis provides new measures that reflect more
accurately the global lesion load in the brain of MS patients, and they may serve
as a method to study the natural course of the disease and as an outcome measure
to evaluate the effect of drugs.
PMID- 9633702
TI - Antibodies against human putamen in children with Tourette syndrome.
AB - BACKGROUND: Similar to the model for Sydenham's chorea, antineuronal antibodies,
which develop in response to a preceding streptococcal infection, have been
speculated to have a role in the development of Tourette syndrome (TS). METHODS:
Serum antibodies against human caudate, putamen, and globus pallidus (interna and
externa) were assayed by enzyme-linked immunosorbent assay (ELISA) and Western
blot techniques and results were correlated with clinical characteristics and
markers of streptococcal infection. SUBJECTS: A total of 41 children with TS
(mean age, 11.3 years) and 39 controls (mean age, 12.1 years) were included.
RESULTS: Compared with controls, TS subjects had a significant increase in the
mean (p=0.006) and median (p=0.002) ELISA optical density (OD) levels of serum
antibodies against putamen, but not caudate or globus pallidus. Western blots on
20 control and 20 TS serum samples showed that specific antibodies to
caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa;
antigens were present in a synaptosomal fraction. TS subjects with a positive
family history of tics had higher OD values (p < or = 0.04), but no association
was shown with age of tic onset, tic severity, sudden onset of tics, or presence
of attention-deficit hyperactivity disorder or obsessive-compulsive disorder.
Risk ratio calculations in TS and control groups and in study subjects
dichotomized for high and low putamen OD values were similar for titers of
antistreptolysin O > or = 166 or antideoxyribonuclease B > or = 170. A subgroup
analysis limited to subjects with elevated streptococcal titers, however, showed
a significantly (p < or = 0.004) larger number of TS subjects with elevated OD
levels. CONCLUSION: Children and adolescents with TS had significantly higher
serum levels of antineuronal antibodies against putamen than did controls, but
their relation to clinical characteristics and markers for streptococcal
infection remains equivocal.
PMID- 9633703
TI - Mouse bioassay versus Western blot assay for botulinum toxin antibodies:
correlation with clinical response.
AB - OBJECTIVE: To compare the mouse protection bioassay (MPB) to the Western blot
assay (WBA) in detecting antibodies against botulinum toxin A (BTX-A) and to
correlate the assay results with clinical responses to BTX-A injections. METHODS:
MPB and WBA assay results were compared in 51 patients (34 nonresponders and 17
responders) who received BTX-A injections, most commonly for cervical dystonia. A
subset of patients received a "test" injection into either the right eyebrow (14)
or right frontalis (12). RESULTS: Twelve patients with antibodies against BTX-A
(Ab+) detected by WBA did not demonstrate antibodies (Ab-) by MPB. Conversely,
five patients were Ab+ by MPB but Ab- by WBA. Specificity of the MPB was 100% on
all three parameters (clinical, eyebrow, and frontalis injections), whereas WBA
specificity was only 71% for clinical response but 100% for both eyebrow and
frontalis responses. Sensitivities for both assays were low (33 to 53%). Of the
16 patients previously Ab+ by MPB, seven became negative on retesting after a
mean interval of 33 months (range, 6 to 93 months). CONCLUSIONS: The lower
specificity of the WBA compared to the MPB suggests that the WBA detects
nonblocking antibodies. Eyebrow and frontalis "test" injections correlated well
with MPB and WBA results and with clinical responses and may be useful in the
evaluation of BTX nonresponders.
PMID- 9633704
TI - Parkinson's disease: improved function with GM1 ganglioside treatment in a
randomized placebo-controlled study.
AB - BACKGROUND/OBJECTIVE: Studies in animal models of Parkinson's disease (PD)
suggest that GM1 ganglioside treatment can restore neurologic and dopaminergic
function. In view of positive preclinical findings and the results of a previous
open-label study demonstrating efficacy of GM1 in PD patients, this study
compared effects of GM1 ganglioside and placebo on motor functions in PD
patients. METHODS: Forty-five patients with mild to moderate PD were studied. The
primary efficacy measure was change in the Unified Parkinson's Disease Rating
Scale (UPDRS) motor score. After three independent baseline assessments, patients
received IV infusion of the test drug (1,000 mg GM1 or placebo) and then self
administered either GM1 or placebo twice daily (200 mg/day, subcutaneously) for
16 weeks. Patients were examined during monthly follow-up visits. RESULTS: There
was a significant difference between groups in UPDRS motor scores at 16 weeks
(p=0.0001). The activities of daily living portion of the UPDRS (off-period
assessment) also showed a significant effect in favor of the GM1-treated patients
(p=0.04). GM1-treated patients also had significantly greater mean improvements
than placebo-treated patients in performance of timed motor tests including tests
of arm, hand, and foot movements, and walking. GM1 was well tolerated and no
serious adverse events were reported. CONCLUSIONS: This study demonstrates that
GM1 ganglioside treatment enhances neurologic function significantly in PD
patients. Further study is warranted to evaluate long-term effects of GM1 in PD
patients and to elucidate further the mechanisms underlying patient improvements.
PMID- 9633705
TI - Progressive supranuclear palsy: a survey of the disease course.
AB - BACKGROUND: The most accurate knowledge about progressive supranuclear palsy
(PSP) comes from small sample studies that preclude precise estimation of the
proportion of PSP patients affected with various symptoms and the examination of
factors predicting survival time. OBJECTIVE: To describe the course of PSP in a
large clinically diagnosed sample of PSP patients and to identify factors
predicting survival time. METHODS: We surveyed the caregivers of 318 living and
119 deceased patients with progressive supranuclear palsy. The main outcome
measures were a principal symptom severity questionnaire and a signs and symptoms
questionnaire. RESULTS: The estimated age of PSP symptom onset depends critically
on how symptom onset is defined, with estimates differing by as much as 1.5
years. Men and women were represented equally (51.6% versus 48.4%) in the living
sample, but men formed 61.8% of the deceased sample. Men were diagnosed later
than women following symptom onset (33.4 versus 24.1 months) and died earlier
following the diagnosis (37.0 versus 47.6 months). Motor and visual symptoms
appeared first, followed by emotional and personality problems, cognitive
impairment, and sleep changes. Whereas motor symptoms eventually affected almost
every patient, emotional/personality and cognitive symptoms did not. The early
onset, presence of falls, slowness, and inability to move eyes downward early in
the development of the disease predicted survival time. CONCLUSION: PSP is a
rapidly progressive disease dominated by motor symptoms, and it affects men more
frequently than women.
PMID- 9633706
TI - Visuomotor control abnormalities in patients with unilateral parkinsonism.
AB - Visuomotor performance is known to be disturbed in patients who have advanced
Parkinson's disease (PD). The degree of impairment in the early stages of PD was
investigated in both the symptomatic and asymptomatic hand of patients with
unilateral disease. We examined the visuomotor performance of 10 early unilateral
parkinsonian patients and 15 control subjects by using several tracing and
tracking tasks that were performed with unseen hands, in which feedback was given
through a screen cursor. Significant impairment in control of movement direction
was found in tracing of screen paths but not in tracking. Significant slowing of
movement was found in target tracking, whereas tracing velocity was normal.
Although all patients were judged by standard clinical criteria to be
unilaterally affected, visuomotor functions were found to be impaired equally in
both hands. Visuomotor control of movement direction and movement velocity is
performed independently. Performance along both control dimensions is impaired in
the mild stages of parkinsonism, even before the appearance of motor symptoms.
PMID- 9633707
TI - Effects of voluntary contraction on tibial nerve somatosensory evoked potentials:
gating of specific cortical responses.
AB - We evaluated vertex-parietal P37, N50, and contralateral N37 somatosensory evoked
potentials (SEPs) to posterior tibial nerve stimulation during weak (20 to 30%)
and strong (80 to 90%) ipsilateral gastrocnemius-soleus contraction. The results
were compared with data obtained during full relaxation. P37 and N50 were
attenuated significantly during weak contraction and then abolished during strong
contraction, whereas the contralateral N37 was not. The N37 potential spreads
over the vertex and over the ipsilateral parietal region during strong
contraction. The Cz'-F3 montage was not appropriate for detecting these SEP
patterns. These findings suggest that thalamic or cortical gating mechanisms
affect specific cortical responses. P37 and N50 could reflect the arrival of the
afferent volley into the motor areas from thalamic and cortical (subareas 1 and 2
of S1) projections. N37 could be generated in subarea 3b. Differential analysis
of N37 and P37 is required in clinical practice, mainly in those conditions that
involve the motor system and in those conditions in which tonic muscular activity
is increased.
PMID- 9633708
TI - Practice styles of US compared to UK neurologists.
AB - OBJECTIVE: This study assessed variation between neurologists in the United
States and United Kingdom in their diagnostic and treatment decisions for
commonly encountered neurologic presentations, and identified explanatory factors
for any observed variation. METHODS: All 210 consultant neurologists in the
United Kingdom and a nationally representative sample of 595 US neurologists
received mailed surveys containing three detailed clinical scenarios depicting
patients with (1) a single unprovoked seizure occurring 3 days previously, (2)
early Parkinson's disease, and (3) dementia. The main study outcome measures were
self-reported decisions regarding diagnostic test ordering and treatment, which
were assessed after each scenario. Neurologists' practice characteristics,
certainty about the diagnosis, and attitudes toward uncertainty were also
measured. Survey response rates were 92% of US and 63% of UK neurologists.
RESULTS: A higher proportion of US than UK neurologists indicated they would
order additional diagnostic tests for all three scenarios (all p < 0.05); 77% of
UK compared with 26% of US neurologists would manage a single unprovoked seizure
without antiepileptic medication (p < 0.0001), but treatment of early Parkinson's
disease was not different. Nearly all US and UK neurologists would obtain a
neuroimaging study in the evaluation of dementia. International differences
persisted after adjustment for differences in demographic and practice
characteristics and for attitudes toward test use and clinical uncertainty.
CONCLUSIONS: We identified large international variation in clinical decisions
across three common neurologic conditions. Cross-country collaboration should
explore these differences to develop consensus on standards of care.
PMID- 9633709
TI - Ischemic stroke: outcomes, patient mix, and practice variation for neurologists
and generalists in a community.
AB - A variety of methods was used to compare patient mix, practice variation,
survival, and recurrence after first ischemic stroke among Rochester, MN
residents. The significance of the results for neurologists and generalists was
examined. Age, stroke severity, congestive heart failure (CHF), and the
interaction between atrial fibrillation and patient groups were determinants of
survival. Without atrial fibrillation, patients on neurology services and
patients on general services with neurology consultation had better survival than
those without neurology consultation, adjusting for age, stroke severity, and
CHF. With atrial fibrillation, patients on general services with neurology
consultation had no better survival compared with those without neurology
consultation; patients on neurology services had worse survival (p=0.002). There
was no difference in stroke recurrence. Evaluation by a neurologist is associated
with better survival for most patients with ischemic stroke but not those with
atrial fibrillation. Only a randomized trial can determine whether this
association is causal.
PMID- 9633710
TI - Cognitive screening examinations for silent cerebral infarcts in sickle cell
disease.
AB - OBJECTIVE: In children with sickle cell disease (SCD), silent cerebral infarcts
are the most frequent cause of neurologic injury. We determined the sensitivity
and specificity of selective neurocognitive measures when separating children
with silent cerebral infarcts and SCD from sibling controls. Additionally, we
tested the validity of the same cognitive measures to identify patients with
overt strokes. METHODS: We examined performance on a neuropsychologic battery
containing measures of attention/executive, spatial, language, memory, and motor
functioning for seven children with SCD and silent cerebral infarct, 21 children
with SCD and overt stroke, and 17 normal siblings. Diagnosis of cerebral infarct
was based on results of MRI. RESULTS: Measures from the attention and executive
domains were the most useful for identifying children with silent cerebral
infarct. The Test of Variables of Attention was the most robust measure and
yielded a sensitivity rate of 86% and a specificity rate of 81%. This measure
also showed a sensitivity rate of 95% in identifying overt stroke. CONCLUSIONS:
Brief cognitive screening measures, if properly constructed, may be an effective
means of identifying children with silent cerebral infarct. Future prospective
studies should be pursued to assess the utility of cognitive screening for silent
cerebral infarcts in SCD.
PMID- 9633711
TI - Pneumatic sequential compression reduces the risk of deep vein thrombosis in
stroke patients.
AB - OBJECTIVE: To determine if pneumatic sequential compression devices (SCDs)
combined with subcutaneous heparin and antiembolic hose reduce the risk of deep
vein thrombosis (DVT) and pulmonary embolism (PE) in stroke patients. BACKGROUND:
DVTs and PEs are serious complications among hospitalized stroke patients.
Subcutaneous heparin and SCDs have both been used to prevent DVT. It is not known
if SCDs combined with subcutaneous heparin can improve the protection afforded by
heparin alone. METHODS: The study group was comprised of nonhemorrhagic stroke
patients admitted to the neurology service from October 1988 through June 1996.
From October 1988 through April 1991 (233 patients), and during February 1993 (16
patients), patients received 5,000 U subcutaneous heparin twice daily and
antiembolic hose. From June 1991 through January 1993 and from March 1993 through
June 1996 (432 patients) all nonambulatory stroke patients had SCDs applied to
both legs in addition to subcutaneous heparin and antiembolic hose. RESULTS:
Twenty-three of 249 patients (9.2%; 21 of 233 and two of 16 patients) treated
with heparin alone developed DVT and six patients (2.4%) developed PE (six of 233
and zero of 16). Half the PE cases (three of six) were fatal and all PEs were in
patients with DVT. Eighty-three of the 249 patients were nonambulatory. Twenty
two of the 23 DVTs and all the PEs developed in nonambulatory patients. Only one
DVT (0.23%) and no PEs occurred among the 432 patients (148 nonambulatory)
treated with SCDs as well as heparin. The addition of SCDs resulted in more than
a 40-fold reduction in the risk of DVT. CONCLUSIONS: Nonambulatory stroke
patients have an increased risk for DVT and PE. Adding SCDs to treatment with
subcutaneous heparin and antiembolic hose reduced the risks of DVTs and PEs. SCDs
should be considered for adjunctive DVT prophylaxis in nonambulatory stroke
patients.
PMID- 9633712
TI - Illicit drug-associated ischemic stroke in the Baltimore-Washington Young Stroke
Study.
AB - BACKGROUND: Limited information exists on the frequency, trends in occurrence,
risk factors, mechanisms, and outcome of ischemic stroke associated with illicit
drug use among young adults in a geographically defined population. METHODS: We
reviewed ischemic stroke in young adults (aged 15 to 44 years) in 46 regional
hospitals for 1988 and 1991. We examined stroke mechanisms and outcome in
patients with recent drug use. RESULTS: Recent illicit drug use was noted in
51/422 (12.1%) stroke patients. Patients with drug use were more likely than
other stroke patients to be black (p=0.01), aged 25 to 39 years (p=0.004), and
smokers (p=0.006), and were less likely to have hypertension (p=0.004) or
diabetes mellitus (p=0.004). Drug use was the probable cause of stroke in 20
(4.7%) patients. Among 31 (7.3%) patients with drug use as a possible stroke
mechanism, more likely diagnoses included cardioembolic stroke in 18,
hematologic/collagen vascular in 6, nonatherosclerotic vasculopathy in 5, and
atherosclerosis in 3. There was no difference in outcome between drug-associated
and non-drug associated stroke. CONCLUSIONS: Recent illicit drug use occurs in
12.1% of young adult stroke patients. Drug-associated young adult stroke seems to
relate to vascular mechanisms other than those related to hypertension or
diabetes. Case-control studies are needed.
PMID- 9633713
TI - Dolichoectasia of the intracranial arteries in patients with first ischemic
stroke: a population-based study.
AB - OBJECTIVE: The objective of this study was to estimate the frequency of
intracranial arterial dolichoectasia among patients with first ischemic stroke
and to compare clinical characteristics, survival, and recurrence in those with
and without the abnormality. BACKGROUND: Dolichoectasia may cause cerebral
infarction by thrombosis, embolism, stenosis, or occlusion of deep penetrating
arteries. METHODS: The chi-square, Fisher's exact, and logrank tests were used to
compare clinical characteristics, survival, and recurrence for patients with and
without dolichoectasia among the 387 residents of Rochester, MN, who had brain CT
or MRI for first cerebral infarction from 1985 through 1989. RESULTS: Twelve
patients (3.1%) had dolichoectasia. Patients with dolichoectasia were more likely
to have had stroke fitting a clinical and radiographic pattern of lacunar
infarction than those without (42% and 17% respectively; p=0.04). Dolichoectasia
was detected in the vertebrobasilar system in eight patients (66.7%), in the
carotid system in two patients (16.7%), and in both circulatory systems in two
patients (16.7%). There were no significant differences in the following
characteristics among those with and without dolichoectasia: age, sex,
hypertension, diabetes, smoking, and preceding transient ischemic attack.
Patients with dolichoectasia had better survival (relative risk [RR] for death,
0.26; p=0.04) after first cerebral infarction but higher rates of stroke
recurrence (RR, 2.4; p=0.02). CONCLUSIONS: Dolichoectasia is detected in 38 of
patients with first cerebral infarction and is associated with better survival
but higher rates of stroke recurrence.
PMID- 9633714
TI - Arterial territories of the human brain: cerebral hemispheres.
AB - The development of neuroimaging has allowed clinicians to improve clinicoanatomic
correlations in patients with stroke. Anatomic structures are well delineated on
MRI, but there is a lack of standardization in their arterial supply. As in our
previous study depicting the arterial supply of the brainstem and cerebellum, we
present a system of 12 axial sections of the hemispheres depicting the dominant
arterial territories, the most important anatomic structures, and Brodmann's
areas. The area of variation of the cortical territory of the anterior, middle,
and posterior cerebral arteries is also represented. These sections may be used
as a practical tool to determine arterial territories on CT or MRI, and may help
establish consistent clinicoanatomic correlations in patients with supratentorial
stroke.
PMID- 9633715
TI - A longitudinal study of patients with venous malformations: documentation of a
negligible hemorrhage risk and benign natural history.
AB - BACKGROUND: The natural history of cerebral venous malformations has not been
well documented, and the clinical significance of these common lesions remains
controversial. OBJECTIVE: The objective of this study was to follow
longitudinally the clinical course of patients with cerebral venous malformations
to document the natural history of the lesion. METHODS: Ninety-two patients with
radiographically confirmed venous malformations were entered into the study
between 1987 and 1996. Annual follow-up was maintained by clinic visits and/or
phone interviews. Sixty-three patients (25 men and 38 women) with more than 1
year of follow-up were analyzed. McNemar's test and logistic regression analysis
was applied to prevalence of presenting symptoms over time. An average per
patient follow-up of 4.2 years yielded 2,721 retrospective and 301 prospective
lesion-years for analysis. RESULTS: Average age at diagnosis was 39.1 years (SD,
18.7 years; range, 2 to 73 years). The most frequent lesion locations included
the frontal lobe (55.6%, n=35) and the cerebellum (27%, n=17). The most frequent
presentations included headache (50.8%, n=32), focal neurologic deficits (39.7%,
n=25), and seizure (30.2%, n=19). Prevalence of headache (p=0.048) and seizure
(p=0.016) decreased over time without treatment of the lesion. A second
cerebrovascular lesion was identified in 12 patients (19%). Two patients had a
symptomatic intracerebral hemorrhage attributable to their venous malformation.
Risk of hemorrhage was 0.15% per lesion-year (95% CI, 0.06 to 0.38%).
CONCLUSIONS: This study establishes that the natural history of venous
malformations is benign, that the risk of hemorrhage from these lesions is
negligible, and that conservative therapy is warranted.
PMID- 9633716
TI - SPECT study of a German CADASIL family: a phenotype with migraine and progressive
dementia only.
AB - OBJECTIVE: We describe the clinical, molecular, genetic, MRI, and SPECT features
of a German family with autosomal dominant migraine and dementia, mapping to the
cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL) locus. We studied the correlation of cerebral blood
flow, MRI, and cognitive function. BACKGROUND: CADASIL is a small-vessel disease
of the brain mapped to chromosome 19p13.1. Mutations of the Notch3 gene cause
this disorder. Most phenotypes are characterized by transient ischemic attacks
(TIAs) and lacunar strokes leading to dementia. Migraine is frequent. A single
photon emission computed tomographic (SPECT) study of this disorder has not yet
been published. METHODS: We studied 13 individuals clinically and performed
neuroimaging studies with MRI and SPECT. RESULTS: Genetic analysis strongly
supported linkage to the CADASIL locus, and the disease haplotype was found in
six individuals. Analysis by single-strand confirmation polymorphism did not
identify Notch3 mutations. All affected individuals had MRI white matter
hyperintensities and four individuals had additional basal ganglial signal
abnormalities. Four affected individuals had migraine, two of whom had slowly
progressive dementia. TIAs, stroke, and focal neurologic signs were absent.
Cerebral blood flow reduction in SPECT studies of affected individuals matched
with MRI signal abnormalities. Cognitive impairment was linked to signal
abnormalities and hypoperfusion in the basal ganglia. Demented patients had a
pattern of frontal, temporal, and basal ganglial hypoperfusion. CONCLUSIONS: We
describe a CADASIL phenotype that is characterized by the absence of focal
neurologic symptoms and present the first SPECT study of this disorder.
PMID- 9633717
TI - Persistent inflammatory response in stroke survivors.
AB - OBJECTIVE: Goals were to determine how long acute-phase markers remain elevated
after ischemic stroke and how marker levels relate to stroke risk factors, stroke
mechanism, and subsequent vascular events. METHODS: Fibrinogen (FIB), C-reactive
protein (CRP), leukocytes (WBC), neutrophils (PMN), interleukin-6, and
interleukin-1 receptor antagonist were measured at stroke onset and at 6 weeks, 6
months, and 1 year after enrollment, or until a vascular event occurred in 136
acute ischemic stroke patients, 76 patients with comparable risk factors for
stroke, and 48 age-balanced healthy subjects. RESULTS: Multivariate logistic
analysis showed that prior stroke and FIB level predicted new events in stroke
patients (p < 0.04 for both), whereas congestive heart failure (p < 0.02) and
creatinine level (p < 0.006) were predictive in at-risk patients. After
controlling for infection, FIB, CRP, and PMN levels at baseline were higher in at
risk but not in stroke patients with recurrent events (p < 0.05 for all). At 1
year, FIB levels remained elevated in event-free stroke survivors compared with
levels in the risk and control groups (p < 0.001 for both). FIB also remained
higher in stroke survivors who had atheroembolism (AE) compared with non-AE
stroke survivors (381+/-72 versus 342+/-78 mg/dL, p < 0.02). Peripheral vascular
disease was an independent predictor (p < 0.0001) of longitudinal FIB in stroke
survivors. Of note, both WBC and PMN levels were chronically elevated in patients
with stroke risk factors and in stroke survivors (p < 0.0001 for both) compared
with healthy elderly subjects. CONCLUSIONS: Most acute-phase markers decline
gradually after stroke, but FIB remains significantly elevated and is associated
with increased risk for recurrent vascular events.
PMID- 9633718
TI - Childhood headache at school entry: a controlled clinical study.
AB - OBJECTIVE: Our objective was to study the prevalence of different headache types,
characterizations, and triggers of headache in Finnish children starting school.
METHODS: Questionnaires were sent to 1,132 families with 6-year-old children.
Children with headache disturbing their daily activities (n=96) and an
asymptomatic control group of children (n=96) participated in a clinical
interview and examination. RESULTS: Children with headache had significantly more
bruxism (odds ratio [OR], 1.9; 95% CI, 1.0 to 3.4), tenderness in the occipital
muscle insertion areas (OR, 4.8; 95% CI, 1.8 to 12.7), and tenderness in the
temporomandibular joint areas (OR, 2.8; 95% CI, 1.3 to 6.0). They also had more
travel sickness (OR, 3.4; 95% CI, 1.7 to 6.7) than control children. Eating ice
cream (OR, 5.3; 95% CI, 1.4 to 20.3), fear (OR, 3.7; 95% CI, 1.2 to 11.2), and
anxiety (OR, 3.2; 95% CI, 1.0 to 10.8) triggered headache more often in
migraineurs than in children with tension-type headache. Children with migraine
also reported more frequently abdominal (OR, 5.6; 95% CI, 1.7 to 18.1) and other
(OR, 3.5; 95% CI, 1.2 to 9.8) pain concurrently with headache, and they used
medication for pain relief more often (OR, 3.1; 95% CI, 1.0 to 9.5). CONCLUSIONS:
Headache classification in children may be improved by palpation of occipital
muscle insertions and temporomandibular joint areas, and by discerning a history
of triggering events and concurrent symptoms.
PMID- 9633719
TI - Global cerebral blood flow, blood volume, and oxygen metabolism in patients with
migraine headache.
AB - OBJECTIVE: Migraine headaches with and without aura are representative of
vascular headache states traditionally thought to be mediated by alterations in
vascular tone. Validation of this theory has been hampered in part by technical
difficulties inherent in the measurement of cerebral blood flow (CBF). The
purpose of this study was to compare CBF measured during migraine and migraine
free states using PET. METHODS: Patients with a minimum of one migraine headache
without aura per month (International Headache Society [IHS] criteria) underwent
measurement of CBF, cerebral blood volume (CBV), oxygen extraction, and
metabolism during an episode of spontaneous migraine headache. Imaging was
repeated during a migraine-free period of at least 48 hours. PET radiotracers
used were: CBF, H(2)15O; CBV, C15O; oxygen metabolism, 15O2. RESULTS: In nine
patients (seven female and two male), global CBF (mL/min/100 g [SD]) was measured
as 52.70 (6.9) during migraine and 59.65 (10.6) in the migraine-free state;
p=0.028. CBV (mL/100 g [SD]) was 3.6 (0.43) during the symptomatic state and 3.8
(0.55) after the migraine; p=0.047. Oxygen metabolism (mL/min/100 g [SD]) was
3.68 (0.9) during migraine and 3.38 (1.02) without headache; p=0.211. The oxygen
extraction ratio was 0.48 (0.15) and 0.41 (0.12) during migraine and migraine
free states, respectively; p=0.132. CONCLUSIONS: In patients experiencing
migraine without aura, CBF and CBV are reduced during the headache phase.
Cerebral oxygen metabolism and oxygen extraction are not significantly affected.
PMID- 9633720
TI - Migraine and reduced work performance: a population-based diary study.
AB - OBJECTIVE: This article estimates lost work days and lost work day equivalents in
a population sample of migraineurs, differentiating work loss due to headache
episodes that met criteria for migraine from migrainous headaches not meeting
full criteria and nonmigrainous headaches. METHODS: A random digit dialing survey
of 5,071 adults identified 800 subjects with migraine headaches. By clinical
examination, a subsample of 225 met migraine diagnostic criteria; 174 of these
patients completed at least 11 weeks of daily diaries. This report concerns the
subgroup of 122 individuals with regular paid employment. Subjects completed a
daily diary over a 3-month period to assess the occurrence of headaches and
International Headache Society (IHS) criteria for each headache occurrence. We
report estimates of lost work days and lost work day equivalents by type of
headache. RESULTS: Participants reported headaches on 8.1 work days, of which 2.2
headache days met criteria for migraine (IHS 1.1, 1.2), and an additional 2.1
headache days were migrainous without meeting full migraine criteria (IHS 1.7).
On average, migraineurs missed 1.1 days of work due to headache in 3 months, of
which 0.7 lost work days were due to migraine and 0.3 were due to migrainous
headaches. When at work with headache, work effectiveness was reduced 41% for
migraine headaches, 28% for migrainous headaches, and 24% for other headaches.
Over 3 months, migraineurs experienced an average of 3.0 lost work day
equivalents, of which 1.4 were due to migraine and an additional 0.7 were due to
migrainous headaches. The most disabled 20% of the participants accounted for 77%
of the lost work days; 40% of subjects accounted for 75% of the lost work day
equivalents. CONCLUSIONS: Employed migraine sufferers experienced considerable
work loss and reduced work performance due to headache. The most severely
affected migraineurs accounted for most of the reduced work performance.
Targeting the most severely affected persons may be necessary to reduce work loss
among migraineurs substantially.
PMID- 9633721
TI - Quantitative analysis of cerebral vasculopathy in patients with Fabry disease.
AB - OBJECTIVE: This study's purpose was to obtain a quantitative natural history of
the cerebrovascular involvement in Fabry disease. BACKGROUND: Fabry disease is an
X-linked recessive disorder due to alpha-galactosidase A deficiency. Progressive
accumulation of ceramidetrihexoside within the intima and media of cerebral blood
vessels causes ischemic lesions in the majority of affected patients.
Determination of the natural history of the cerebral vasculopathy in Fabry
disease is important to assess the effects of therapeutic intervention in this
disorder. METHODS: A longitudinal MRI study of 50 patients who had a total of 129
MRI scans was performed. The burden of cerebrovascular disease was determined
using direct linear measurement. RESULTS: On T2-weighted MRI scans, 32% of the
patients had no lesions (mean age, 33 years), 16% had gray matter lesions only
(mean age, 36 years), 26% had lesions in white matter only (mean age, 43 years),
and 26% had lesions in white and gray matter (mean age, 47 years). Disease burden
increased with age, but no patient younger than 26 had lesions on MRI. All
patients older than 54 had cerebrovascular involvement. The distribution of MRI
detectable lesions was typical of a small-vessel disease. Only 37.5% of patients
with cerebral lesions had neurologic symptoms. CONCLUSION: These findings provide
a predictable outcome measure to assess the effect of molecular interventions on
the cerebrovascular circulation in Fabry disease.
PMID- 9633722
TI - Duplication of the proteolipid protein gene is the major cause of Pelizaeus
Merzbacher disease.
AB - BACKGROUND/OBJECTIVE: Pelizaeus-Merzbacher disease (PMD), an X-linked recessive
dysmyelination disorder, is caused by mutations in the proteolipid protein (PLP)
gene. However, missense mutations were only found in a fraction of PMD patients,
even in families that showed linkage with the PLP locus on Xq22. Here we describe
the use of an extended protocol that includes screening for both missense
mutations and duplications. METHOD: Two groups of patients were analyzed, one
group with 10 independent PMD families and one group with 24 sporadic patients
suspected of PMD. Missense mutations in the PLP gene were identified by
sequencing. PLP gene duplications were detected by quantitative polymerase chain
reaction and/or Southern blot analysis. RESULTS: Sequencing of the PLP gene
revealed four mutations in group 1 and one mutation in group 2. However,
inclusion of duplication analysis in the screening protocol raised the amount of
mutations found in group 1 from 40 to 90%, and in group 2 from 4 to 25%.
CONCLUSIONS: These results demonstrate that duplications of the PLP gene are the
major cause of PMD. Furthermore, it appears that the phenotype resulting from PLP
duplications is relatively mild, and that many probands are nontypical PMD
patients.
PMID- 9633723
TI - CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform
lesions.
AB - OBJECTIVE: The authors examined the incidence and radiologic characteristics of
plexiform neurofibromas in neurofibromatosis-1 (NF-1) to define a cohort at
greatest risk for malignant nerve-sheath tumors. BACKGROUND: Plexiform
neurofibromas are a frequent complication of NF-1. They can impair function,
produce disfigurement, and be the site for the development of malignant nerve
sheath tumors. The incidence and natural history of plexiform neurofibromas is
unknown. METHODS: CT imaging of the chest, abdomen, and pelvis was performed in
91 of 125 consecutive adults (age, > or = 16 years) with NF-1. RESULTS: Twenty
percent of patients had plexiform neurofibromas of the chest in the paraspinal,
mediastinal, or supraclavicular area. Approximately 40% of patients had abnormal
abdominal/pelvic scans. The paraspinal, sacral plexus, sciatic notch, and
perirectal regions were the most common sites. Most plexiform neurofibromas were
asymptomatic. Imaging also revealed a number of tumors, including malignant nerve
sheath tumors, adrenal tumors, carcinoids, and schwannomas. CONCLUSIONS: The
frequency of plexiform lesions and other tumors in NF-1 indicates that clinicians
should monitor young adults carefully; however, imaging characteristics alone
cannot reliably distinguish benign from malignant lesions.
PMID- 9633724
TI - Tethered cord syndrome in occult spinal dysraphism: timing and outcome of
surgical release.
AB - OBJECTIVE: To investigate the influence of neurosurgical intervention on the
appearance of upper motor neuron (UMN) signs in newborns diagnosed with occult
spinal dysraphism and tethered cord (TC) during the first month of life. METHODS:
A prospective study (1990 to 1996) of 22 consecutive newborns with occult spinal
dysraphism monitored for the appearance of UMN signs. Untethering was performed
when neurologic or urodynamic investigation indicated the presence of UMN
dysfunction. RESULTS: Of 22 patients, 10 remained free of UMN symptoms during
follow-up (mean, 67+/-22 months). Untethering was performed in 12 of 22 patients
because of the presence of UMN symptoms. In 7 of these 12 patients, there was a
documented asymptomatic period of 13+/-11 months before the onset of UMN
symptoms. Untethering at a mean age of 18+/-17 months restored normal neurologic
and urinary function in all patients (mean postoperative follow-up, 25+/-16
months). Of the 12 children, 5 presented with UMN signs at birth. In these
children, untethering was performed at a mean age of 9+/-5 months. In two of
these five patients, UMN symptoms did not resolve after surgery, and ongoing
conservative bladder treatment was required (mean follow-up, 37+/-14 months). In
none of the 12 operated children did signs of retethering occur. CONCLUSIONS: A
significant number (10/22) of children born with occult spinal dysraphism and TC
did not develop UMN symptoms during follow-up; neurosurgical correction after the
appearance of an UMN sign restored normal neurologic and urinary function in all
children; and untethering in children presenting at birth with UMN symptoms
resulted in poorer outcome.
PMID- 9633725
TI - EEG findings in frontal lobe epilepsies.
AB - As a group, epilepsies of frontal lobe origin are thought to be poorly localized
using surface EEG recordings. This finding may depend on the specific areas of
frontal lobe from which the seizures originate or the pathologic substrate. We
reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who
underwent epilepsy surgery. The specific area of the frontal lobe where seizures
originated was determined by 1) intracranial ictal EEG recordings, or 2) the
presence of a structural lesion, identified by imaging studies in patients who
achieved complete seizure control following surgery. We differentiated patients
whose seizures began in the dorsolateral frontal convexity from those whose
seizures began in the medial frontal region, and we correlated EEG findings in
the interictal, postictal, and ictal states with seizure semiology, pathologic
substrate, and surgical outcome. Four of nine patients had seizures originating
in the dorsolateral frontal convexity and five had medial frontal onset seizures.
Patients whose seizures originated from the dorsolateral convexity had focal
interictal epileptiform abnormalities that localized to the region of seizure
onset. Patients whose seizures began in the medial frontal region had either no
interictal epileptiform abnormality or had multifocal epileptiform discharges.
Patients whose seizures began in the dorsolateral convexity showed focal
electrographic seizure activity that was localizing. This rhythmic fast activity
did not appear to be substrate-specific. Patients whose seizure onset localized
to the medial frontal region did not show focal electrographic seizure at
clinical onset. We conclude that the scalp EEG recordings of frontal lobe
epilepsies contain features that enable differentiation of seizures originating
from two different regions of the frontal lobe.
PMID- 9633726
TI - Nocturnal temporal lobe epilepsy.
AB - OBJECTIVE: To analyze clinical, electrophysiologic, and neuroradiologic
characteristics and prognostic factors in a group of patients with temporal lobe
epilepsy (TLE) and complex partial seizures (CPS) occurring exclusively or
predominantly after they fall asleep or before they awaken. BACKGROUND: CPS
arising during sleep are classically identified with frontal lobe epilepsy. TLE
associated with seizures occurring only or predominantly during sleep (nocturnal
TLE) is less common. METHODS: From a series of patients with refractory TLE
studied between 1980 and 1996, the authors identified 26 patients (15 men) with
nonlesional nocturnal TLE (mean age, 40 years). Clinical and laboratory
characteristics of these individuals were studied and compared with a group of 72
age-matched, randomly selected patients with nonlesional TLE and predominantly
diurnal seizures (diurnal TLE). RESULTS: Mean age at seizure onset was similar
for both groups (16.3 versus 18.7 years). In the nocturnal TLE group, 2 of 26
patients had a positive family history of epilepsy, 18 reported an aura, 4
presented with CPS in clusters, 11 had unilateral and 15 bilateral temporal EEG
abnormalities, and 14 of 21 studied had unilateral mesial temporal atrophy. None
of these factors differed significantly in the two groups except for higher
frequency of the following in the diurnal TLE group compared with the nocturnal
TLE group: positive family history for epilepsy (33% versus 8%, p=0.01),
estimated frequency of seizures (median, 14 versus 2 per month; p < 0.01), and
presence of antecedent febrile convulsions (33% versus 11%, p=0.04). In the
nocturnal TLE group, eight patients underwent surgical therapy and became seizure
free (follow-up, > 12 months). Only two were seizure free on medication.
CONCLUSIONS: Infrequent and nonclustered seizures, rare family history of
epilepsy, and low prevalence of childhood febrile convulsions characterize
nocturnal TLE. Within the TLEs, the nocturnal TLE form seems to have a better
surgical prognosis.
PMID- 9633727
TI - A randomized double-blind trial of prednisolone alone or with azathioprine in
myasthenia gravis. Myasthenia Gravis Study Group.
AB - We compared prednisolone (PRED) and azathioprine (AZA) versus prednisolone alone
in the treatment of MG. Prednisolone alone or combined with azathioprine is
widely used in the treatment of MG, but no randomized placebo-controlled
comparative trial data are available. The prednisolone dose and clinical outcome
were compared in a multicenter randomized double-blind study of 34 MG patients
who were followed up for 3 years. One group (PRED + AZA) received prednisolone
(on alternate days) plus azathioprine (2.5 mg/kg); the other group received
prednisolone on alternate days plus placebo (PRED + PLAC). Initial high-dose
prednisolone (1.5 mg/kg on alternate days) was tapered at remission to the
minimal dose required to maintain remission. The prednisolone dose did not differ
significantly between the two groups at 1 year (median values: PRED + AZA, 37.5
mg on alternate days; PRED + PLAC, 45 mg on alternate days) but was reduced at 2
and 3 years in the PRED + AZA group (median value at 3 years: PRED + AZA, 0 mg on
alternate days; PRED + PLAC, 40 mg on alternate days; p=0.02). Relapses and
failures to remit over the 3 years were more frequent in the PRED + PLAC group.
There was a sharp rise in the anti-acetylcholine receptor (AChR) titers in the
PRED + PLAC group at 2 years. Incidence of side effects was slightly less in the
PRED + AZA group. Azathioprine as an adjunct to alternate day prednisolone in the
treatment of antibody-positive generalized MG reduces the maintenance dose of
prednisolone and is associated with fewer treatment failures, longer remissions,
and fewer side effects.
PMID- 9633728
TI - Clinical manifestations of mitochondrial DNA depletion.
AB - OBJECTIVE: We studied five new patients with mitochondrial DNA (mtDNA) depletion
to better define the clinical spectrum of this disorder. BACKGROUND: mtDNA
depletion has been associated with myopathy or hepatopathy, or both, in infants
and young children. Involvement of the CNS and peripheral nervous system has not
been clearly established. METHODS: We reviewed the clinical course and performed
morphologic, biochemical, and genetic analyses of muscle samples from five
patients. RESULTS: Age at onset ranged from 3 months to 5 years, and one patient
survived until age 10 1/2 years. Two patients had laboratory and clinical
features reminiscent of dystrophinopathy, two had evidence of brain involvement,
and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed
abundant ragged-red fibers. Biochemistry showed cytochrome c oxidase deficiency
in all patients tested and decreased activities of other respiratory chain
complexes in some. CONCLUSIONS: Inheritance appeared to be autosomal recessive,
suggesting that mutations in nuclear DNA are responsible for mtDNA depletion.
mtDNA depletion should be considered in children with mitochondrial disorders of
uncertain etiology, and criteria for diagnosis are proposed.
PMID- 9633729
TI - Epilepsy and mental retardation in a subset of early onset 4q35
facioscapulohumeral muscular dystrophy.
AB - The gene for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to
chromosome 4q35. In most patients with FSHD, a deletion of 3.3 kb tandemly
repeated units within the EcoRI fragment that can be detected by probe p13E-11 is
associated with the disease. To elucidate the relation between the phenotype and
the genotype in FSHD, we examined 91 Japanese unrelated families with a clinical
diagnosis of FSHD (140 patients, 205 healthy individuals). Of these, 78 families
(86%) had 4q35-FSHD (127 patients), in which 20 patients (20/127, 16%) were
classified as early onset FSHD. We found that all nine patients with the smallest
EcoRI fragments (10 to 11 kb) were classified among the early onset group (9/20,
45%), and these patients showed a high frequency of both epilepsy (4/9, 44%) and
mental retardation (8/9, 89%). In contrast, none of the remaining patients with
4q35-FSHD had epilepsy or mental retardation. We conclude that FSHD patients with
a large gene deletion in the FSHD gene region tend to have a higher chance of
showing severe clinical phenotypes with CNS abnormalities. This finding may have
practical implications for genetic counseling, although the molecular genetic
background remains unclear.
PMID- 9633730
TI - Primary hyperparathyroidism and ALS: is there a relation?
AB - BACKGROUND: An association between primary hyperparathyroidism (PHP) and
amyotrophic lateral sclerosis (ALS) has been noted; however, a causal relation
between these disorders has not been confirmed. PATIENTS/METHODS: We report five
patients (three men, two women) meeting El Escorial criteria for ALS who also had
PHP. In three patients, the diagnosis of PHP was made during the laboratory
evaluation for motor neuron disease, and in one patient, the diagnosis of PHP
preceded the onset of weakness by 5 months and in another by 2 years. Serum
calcium levels in all five patients were elevated, ranging from 11.2 to 12.8
mg/dL (normal, <10.4 mg/dL), as were levels of parathyroid hormone (PTH).
RESULTS: All five patients underwent parathyroid adenoma resection with
subsequent normalization of serum calcium and PTH levels. Each patient had
progressive weakness resulting in death 1 to 3 years following parathyroidectomy.
CONCLUSION: Resection of parathyroid adenomas in patients meeting El Escorial
criteria for ALS did not alter the course of ALS. PHP and ALS appear to be
coexisting but unrelated disorders.
PMID- 9633731
TI - Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS.
AB - The primary objectives of this study were to test whether 1) N-acetylaspartate
(NAA), a neuronal marker, is reduced in motor cortex and corticospinal-tract
(CST) brain regions of ALS patients; and 2) motor cortex NAA correlates to a
clinical measurement of upper motor neuron function in ALS patients. Ten probable
or definite ALS patients and nine neurologically normal control subjects were
studied. Three axial planes of two-dimensional 1H MRSI data were collected, using
a single spin-echo multislice sequence (TE140/TR2000). Two of the 1H MRSI planes
were positioned superior to the lateral ventricles, and one plane was positioned
at the level of the internal capsule. Spectroscopy voxels were selected from
motor cortex, frontal cortex, parietal cortex, medial gray matter, centrum
semiovale white matter, anterior internal capsule, and posterior internal
capsule. Peak integrals were obtained for the three major 1H MRSI singlet
resonances, NAA, creatine and phosphocreatine (Cr), and cholines (Cho). Maximum
finger-tap rate was used as a clinical measurement of upper motor neuron
function. In ALS, brain NAA/(Cho+Cr) was reduced 19% (p=0.024) in the motor
cortex and 16% (p=0.021) in the CST (centrum semiovale and posterior internal
capsule) regions. NAA/ (Cho+Cr) was not reduced in frontal cortex, parietal
cortex, medial gray matter, or anterior internal capsule. There was a significant
relation between ALS motor cortex NAA/(Cho+Cr) and maximum finger-tap rate
(r=0.80; p=0.014). NAA/(Cho+Cr) was reduced in motor cortex and CST regions and
unchanged in other brain regions of ALS patients when compared with controls.
These findings are consistent with the known distribution of neuronal loss in
ALS. The positive correlation between motor cortex NAA/(Cho+Cr) and maximum
finger-tap rate suggests that reduced NAA/(Cho+Cr) is a surrogate marker of motor
cortex neuron loss in ALS. These findings support the study of 1H MRSI NAA
measurement as an objective and quantitative measurement of upper motor neuron
dysfunction in ALS.
PMID- 9633732
TI - Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and
cancer-related syndromes.
AB - BACKGROUND: Autoantibodies specific for the acetylcholine receptor (AChR) of
skeletal muscle (containing the alpha1 subunit) impair neuromuscular transmission
in myasthenia gravis (MG). AChRs mediating fast synaptic transmission through
autonomic ganglia are structurally similar to muscle AChR, but contain the alpha3
subunit. We propose that ganglionic AChR autoimmunity may cause dysautonomia.
OBJECTIVE: To test serum of patients with autonomic neuropathy for autoantibodies
of neuronal ganglionic AChR specificity. METHODS: We developed an
immunoprecipitation radioassay by complexing epibatidine (125I-labeled high
affinity agonist) to a Triton X-100-solubilized AChR antigen from peripheral
neuroblastoma membranes. Monoclonal rat immunoglobulins (IgG) specific for muscle
or neuronal AChRs validated the assay's specificity. We tested serum from 52
healthy subjects, 12 patients with subacute autonomic neuropathy, and 248
patients with other neurologic disorders. RESULTS: Twelve patients had antibodies
that bound unequivocally to ganglionic AChR. Five had subacute autonomic
neuropathy, and three (of six tested) had Isaacs' syndrome; four of these eight
had a carcinoma (lung, bladder, rectum, thyroid). The remaining four seropositive
patients (two Lambert-Eaton syndrome, one dementia, one sensory neuronopathy) all
had Ca2+ channel antibodies and three had small cell lung carcinoma. No healthy
subject had ganglionic AChR antibodies, nor did 62 patients with MG and muscle
AChR antibodies. CONCLUSION: Neuronal AChR antibodies are a novel serologic
marker of neurologic autoimmunity. The pathogenicity of neuronal AChR
autoantibodies in autonomic neuropathy, Isaacs' syndrome, or other neurologic
disorders remains to be shown, as has been demonstrated for muscle AChR
antibodies in MG. An autoimmune and potentially paraneoplastic etiology is
implicated in seropositive patients.
PMID- 9633733
TI - Variable progression of HIV-associated dementia.
AB - A consecutive series of 71 patients diagnosed with HIV-associated dementia (HAD)
(1984-1994) were studied to characterize the clinical course of HAD, and to
identify predictive markers of rapid neurologic progression. Neurologic
progression rate was determined from the change in the Memorial Sloan Kettering
(MSK) dementia severity score from diagnosis to death. Those with the most rapid
progression in neurologic disability were compared with those with slow or no
progression. Autopsy material was immunostained for macrophage activation markers
and gp41 in 30 individuals. Median survival was 3.3 months and 6.1 months for
rapid-progression and no-progression patients, respectively. Rapid progression
was associated with injection drug use but not with race, gender, or age. CD4+
cell counts were lower at diagnosis among rapid-progression than no-progression
patients but no differences in AIDS-defining illnesses or patterns of
antiretroviral therapy were found. At presentation, rapid-progression patients
had more prominent symptoms of mental slowing than those with no progression;
however, no other clinical features, CSF, or imaging features distinguished the
groups. Less abundant macrophage activation in both basal ganglia and midfrontal
gyrus regions, as judged by HAM56 immunostaining, was noted in 9 no-progression
patients, compared with 12 rapid-progression patients. Neurologic progression and
survival with HAD is highly variable. A significant proportion of individuals
with dementia have prolonged survival of more than 12 months and remain
cognitively stable. A history of injection drug use and presentation with
prominent psychomotor slowing is associated with more rapid neurologic
progression, and these patients tend to show more abundant macrophage activation
within the CNS.
PMID- 9633734
TI - Increased cerebral blood volume in HIV-positive patients detected by functional
MRI.
AB - OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection.
BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection.
Physiologic changes in the HIV brain may precede structural changes and may be
detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to
measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7
healthy control subjects. RESULTS: Significant increases in dynamic CBV were
found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive
(HIV+) patients. Patients with definite cognitive impairment showed significantly
greater increases in CBV in the deep gray matter (DGM) compared with those
without impairment. In one patient with rapidly progressive cognitive impairment,
these abnormalities reversed and paralleled clinical improvement after initiation
of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that
HIV infection is associated with significant cerebral hemodynamic changes,
particularly in the DGM, that may contribute to cognitive dysfunction in AIDS.
Functional MRI may be useful for early detection of cerebral injury and for the
assessment of novel therapies.
PMID- 9633735
TI - M. tuberculosis molecular variation in CNS infection: evidence for strain
dependent neurovirulence.
AB - OBJECTIVE: To determine the molecular diversity among Mycobacterium tuberculosis
isolates associated with central nervous system tuberculosis (CNS TB) in a
defined cohort of HIV uninfected patients. DESIGN/METHODS: A retrospective
analysis was performed of clinical and laboratory data for all patients with CNS
TB diagnosed in Manitoba, Canada, between 1979 and 1996. Restriction fragment
length polymorphisms (RFLP) of archival isolates of M. tuberculosis from CNS TB
patients were determined and interpreted against the frequency of different
isolates from all TB patients in the years 1992 to 1996. RESULTS: Among 2,334
patients with active TB, CNS TB was diagnosed in 42 (1.8%); meningitis with or
without tuberculoma in 76%; and tuberculoma alone in 24%. CNS TB patients were
significantly more likely to be young (<40 years old), female, and of Aboriginal
origin. Morbidity (fixed/recurrent CNS deficit) rate was 29% and mortality rate
was 26%. An adverse outcome, either morbidity or mortality, was significantly
more common in those with meningitis. RFLP analysis of isolates (n=19) from CNS
TB patients revealed 13 distinct restriction patterns with a predominance of the
type 1 pattern (n=6). The frequency of type 1 restriction pattern was
significantly greater in patients with CNS TB compared to all TB patients in
Manitoba. CONCLUSIONS: CNS TB continues to have a high morbidity and mortality
despite modern methods of detection and treatment. Although several strains of M.
tuberculosis cause CNS TB, the current study suggests that the occurrence of CNS
TB may be strain-dependent.
PMID- 9633736
TI - Randomized trial comparing two different high doses of methylprednisolone in MS:
a clinical and MRI study.
AB - OBJECTIVE: To assess the efficacy of two different high doses of intravenous
methylprednisolone (IVMP) for the treatment of relapses in MS. BACKGROUND: IVMP
is the treatment of choice for MS relapses, but it is unknown whether its effects
are dose related. METHODS: We conducted a double-blind, randomized study. Follow
up included serial clinical and MRI recordings at baseline and at 7, 15, 30, and
60 days after the beginning of treatment. Outcome measures were the number of
brain and cervical spinal cord MRI contrast-enhancing lesions, and the Expanded
Disability Status Scale score. RESULTS: Both treatment regimens improved clinical
scores and reduced the number of MRI enhancing lesions during the follow-up
period. The higher dose of IVMP was significantly more effective than the lower
dose in reducing the number of MRI contrast-enhanced lesions at 30 and 60 days,
mainly by decreasing the rate of new lesion formation. CONCLUSIONS: The higher
dosage of IVMP has a more powerful and prolonged action in maintaining blood
brain barrier integrity after a clinical relapse.
PMID- 9633737
TI - Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic
neuralgia.
AB - OBJECTIVE: Although opioid analgesics are used in the management of neuropathic
pain syndromes, evidence of their efficacy remains to be established. We
evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using
postherpetic neuralgia as a model. METHODS: Patients with postherpetic neuralgia
of at least moderate intensity were randomized to controlled-release oxycodone 10
mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover
design. The dose was increased weekly up to a possible maximum of 30 mg every 12
hours. Pain intensity and pain relief were assessed daily, and steady (ongoing)
pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were
recorded at weekly visits. Clinical effectiveness, disability, and treatment
preference were also assessed. RESULTS: Fifty patients were enrolled and 38
completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic
neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone
dose during the final week was 45+/-17 mg per day. Compared with placebo,
oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p=0.0001) and
reductions in steady pain (34+/-26 versus 55+/-27 mm, p=0.0001), allodynia (32+/
26 versus 50+/-30 mm, p=0.0004), and paroxysmal spontaneous pain (22+/-24 versus
42+/-32 mm, p=0.0001). Global effectiveness, disability, and masked patient
preference all showed superior scores with oxycodone relative to placebo (1.8+/
1.1 versus 0.7+/-1.0, p=0.0001; 0.3+/-0.8 versus 0.7+/-1.0, p=0.041; 67% versus
11%, p=0.001, respectively). CONCLUSIONS: Controlled-release oxycodone is an
effective analgesic for the management of steady pain, paroxysmal spontaneous
pain, and allodynia, which frequently characterize postherpetic neuralgia.
PMID- 9633738
TI - Double-blind randomized trial of tramadol for the treatment of the pain of
diabetic neuropathy.
AB - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of
diabetic neuropathy is a major cause of morbidity among these patients and
treatment, as with other small-fiber neuropathies, is often unsatisfactory.
Tramadol is a centrally acting analgesic for use in treating moderate to
moderately severe pain. METHODS: This multicenter, outpatient, randomized, double
blind, placebo-controlled, parallel-group study consisted of a washout/screening
phase, during which all analgesics were discontinued, and a 42-day double-blind
treatment phase. A total of 131 patients with painful diabetic neuropathy were
treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered
as identical capsules in divided doses four times daily. The primary efficacy
analysis compared the mean pain intensity scores in the tramadol and placebo
groups obtained at day 42 of the study or at the time of discontinuation.
Secondary efficacy assessments were the pain relief rating scores and a quality
of life evaluation based on daily activities and sleep characteristics. RESULTS:
Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more
effective than placebo for treating the pain of diabetic neuropathy. Patients in
the tramadol group scored significantly better in physical (p=0.02) and social
functioning (p=0.04) ratings than patients in the placebo group. No statistically
significant treatment effects on sleep were identified. The most frequently
occurring adverse events with tramadol were nausea, constipation, headache, and
somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that
tramadol was effective and safe in treating the pain of diabetic neuropathy.
PMID- 9633739
TI - Philadelphia Infirmary for Nervous Diseases: America's original model of
institutional neurology.
AB - The role and contributions of the Philadelphia Orthopedic Hospital and Infirmary
for Nervous Diseases in the development of neurology in 19th-century America are
described. American neurology was largely born during the Civil War through the
work of S.W. Mitchell at Turner's Lane Hospital. With the closing of this
military facility, the United States was left without an institution dedicated to
neurologic research and the treatment of nervous system diseases. Nineteenth
century archival data, including original Trustees' minutes, annual board of
managers reports, patient case books, and published research from the
Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases were studied.
The Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases promoted
the development of neurology in the United States through three main activities.
First, it offered patients with primary nervous system diseases, arthritis, and
orthopedic disorders specialized care that was unavailable at medical
universities. Second, its medical staff, especially Mitchell, provided
opportunities for advanced neurologic education. Postgraduate physicians
interested in neurologic disease attended formal lectures and directly
participated in the operation of outpatient clinics and inpatient rounds.
Finally, its formalized record system in the form of case books facilitated
neurologic research. These records formed the basis of landmark publications by
Mitchell, Sinkler, Osler, and others on rest therapy, spastic palsies, chorea,
and other topics. As America's first and comprehensive peacetime neurologic
facility, the Philadelphia Orthopedic Hospital and Infirmary for Nervous Diseases
fostered the evolution of neurology as a separate, viable specialty in the post
Civil War period and provided a particular focus for the study of interactions
among orthopedic, nutritional, and neurologic disorders.
PMID- 9633740
TI - Spontaneous intracranial hypotension resulting in stupor caused by diencephalic
compression.
AB - A 51-year-old man had a 4-month history of progressive headache and gradual onset
of somnolence. MRI suggested spontaneous intracranial hypotension (SIH) with
diencephalic compression, but he did not improve after three epidural blood
patches. He became alert following intrathecal saline infusion that normalized
his CSF pressure. A CSF leak was noted on spinal MRI and confirmed with CT
contrast myelography. Surgical ligation of a torn dural root sleeve isolating a
ruptured Tarlov's cyst resulted in permanent cure.
PMID- 9633741
TI - Hemopericardium and cardiac tamponade after thrombolysis for acute ischemic
stroke.
AB - Hemorrhage is the major complication of IV recombinant tissue plasminogen
activator (rt-PA) treatment for stroke. We report three patients with mild or
indistinct cardiac symptoms prior to thrombolysis in whom hemodynamically
significant cardiac tamponade occurred after treatment with rt-PA. Acute ischemic
stroke patients may have undetected myocardial or pericardial disease that may
pose a risk for hemopericardium and life-threatening tamponade after treatment
with rt-PA.
PMID- 9633742
TI - Isolated voluntary facial paresis due to pontine ischemia.
AB - We describe a patient with isolated voluntary facial paresis due to a unilateral
lacunar lesion in the contralateral mediodorsal middle base of the pons.
Transcranial magnetic stimulation confirmed the involvement of supranuclear
corticofacial tract fibers and sparing of the corticolingual and corticospinal
connections. This observation demonstrates that the fibers conveying voluntary
orofacial activation descend mediodorsally at the level of the middle pons and
that the fibers conveying emotional activation may be assumed to converge below
this level.
PMID- 9633743
TI - Giant cell arteritis and Vernet's syndrome.
PMID- 9633744
TI - Upper cervical myelopathy associated with low CSF pressure: a complication of
ventriculoperitoneal shunt.
AB - A patient who had undergone ventriculoperitoneal shunting developed upper
cervical myelopathy. His CSF pressure was markedly low, and deformation of the
spinal cord and shrinkage of the subarachnoid space at the upper cervical level
were found in radiologic examinations. Ligation of the shunt tube resulted in
almost complete recovery. The effect of excessive drainage may have caused the
abnormalities.
PMID- 9633745
TI - Congenital bilateral perisylvian polymicrogyria presenting as congenital
hemiplegia.
AB - We report three children with pure congenital hemiplegia found to have congenital
bilateral perisylvian polymicrogyria (CBPP). None of our patients had the
seizures, oromotor dysfunction, or cognitive impairment usually associated with
CBPP. CBPP may be more common and heterogeneous than previously thought, is
easily recognized by MRI, and should be included in the differential diagnosis of
the young child presenting with congenital hemiplegia.
PMID- 9633746
TI - CSF levels of carnitine in children with meningitis, neurologic disorders, acute
gastroenteritis, and seizure.
AB - Carnitine concentrations in CSF, serum, and urine in normal febrile children and
children with meningitis, neurologic disorders, and dehydration were studied.
Carnitine levels in CSF were 1/10 compared with serum in normal febrile children.
These levels increased two- to three-fold in the pathologic conditions studied.
Since damage to the blood-brain barrier occurs in these conditions, higher blood
brain barrier permeability might explain CNS carnitine accumulation.
PMID- 9633747
TI - Creutzfeldt-Jakob disease (CJD) after blood product transfusion from a donor with
CJD.
AB - We report a second case of an association between an albumin transfusion and
Creutzfeldt-Jakob disease. On balance, we believe our case represents a chance
and not a causal relation.
PMID- 9633748
TI - Cefuroxime-induced encephalopathy.
AB - We describe four patients who developed an encephalopathic syndrome characterized
by obtundation or stupor, myoclonic jerks, and asterixis in association with
cefuroxime therapy. Three patients had renal failure. These cases suggest that
cefuroxime in overdose or in conventional doses in patients with renal failure
can cause a reversible encephalopathy. This syndrome may have been unrecognized
because it usually occurs in severely ill patients with additional causes for
encephalopathy.
PMID- 9633749
TI - A new mitochondrial tRNA(Met) gene mutation in a patient with dystrophic muscle
and exercise intolerance.
AB - A 30-year-old woman with a novel heteroplasmic U4409C mtDNA mutation in the
tRNA(Met) gene presented with growth retardation, muscle weakness, severe
exercise intolerance, and lactic acidosis. Muscle biopsy showed unusually severe
dystrophic features. The mutation was not present in maternal relatives or 25
healthy subjects. Single-fiber PCR-RFLP analysis of mtDNA showed higher
proportion of the mutation in COX-negative than in COX-positive muscle fibers.
PMID- 9633750
TI - MRI in juvenile ALS: a patient report.
AB - We describe the MR images of a patient with juvenile ALS. MRI of the brain showed
bilateral hyperintensities along the corticospinal tracts extending from the
corona radiata to the brainstem on T2-weighted images. These findings should be
differentiated from the slight hyperintensities seen in the posterior limbs of
the internal capsules in normal subjects.
PMID- 9633751
TI - Electrophysiological aids in distinguishing organic from psychogenic tremor.
AB - The clinical differentiation of tremors of organic and psychogenic origin can be
difficult. We describe a patient with unilateral upper limb tremor that was
initially considered to have a psychogenic cause, but subsequent frequency
analysis of EMG signals and accelerometer recordings indicated that the tremor
was organic in nature. An ischemic lesion in the contralateral lentiform nucleus
found on MRI supported this conclusion. Quantitative electrophysiologic studies
may thus be useful in distinguishing organic from psychogenic tremor.
PMID- 9633752
TI - High prevalence of parkinsonism after occupational exposure to lead-sulfate
batteries.
AB - Seven of nine postal workers exposed to lead-sulfate batteries over a period of
up to 30 years developed parkinsonian symptoms. One of the remaining two showed
left-hand bradykinesia and one was not available for examination. The high
prevalence and cause of parkinsonism in these patients remains unexplained. Lead
intoxication may play a role in the occurrence of parkinsonian symptoms, but
involvement of sulfate and other sulfur compounds must also be considered.
PMID- 9633753
TI - The brainstem and thalamic lesions in dentatorubral-pallidoluysian atrophy: an
MRI study.
AB - We studied the frequency and characteristics of brainstem and thalamic lesions in
dentatorubral-pallidoluysian atrophy using MRI. Of 15 subjects diagnosed by DNA
analysis, 13 had lesions in the pontine base, nine in the midbrain, and five in
the thalamus. Lesions were correlated positively with the patient's age, but not
with neurologic features or numbers of CAG repeats. Patients with Machado-Joseph
disease or spinocerebellar ataxia 1 did not show these characteristic lesions.
PMID- 9633754
TI - Mood response to levodopa infusion in early Parkinson's disease.
AB - Mood response to levodopa infusion was studied in 18 Parkinson's disease (PD)
patients during the first year of levodopa therapy before and after 2-hour (1.0
mg/kg/h) levodopa infusions at baseline and 6- and 12-month follow-up. Mood
elevation was greatest after a 2-day levodopa holiday at the 6- and 12-month
assessments. Age, sex, duration and severity of PD, and ongoing oral levodopa
dose did not correlate with mood response. Mood response in these patients
differs from that seen in advanced patients, possibly because of sensitization to
levodopa's mood effects.
PMID- 9633755
TI - Unusual ocular motility disturbances with increased intracranial pressure.
AB - We evaluated nine patients with external ophthalmoparesis and increased
intracranial pressure. The eye movements normalized when the intracranial
pressure was controlled. Investigations for an underlying cause of elevated
cerebrospinal fluid pressure are warranted when ocular motility disorders are
present.
PMID- 9633756
TI - Visual activation patterns in patients with optic neuritis: an fMRI pilot study.
AB - We studied the use of functional MRI (fMRI) with visual stimulation in nine
patients with unilateral optic neuritis. Eight healthy subjects served as
controls. Patients showed reduced activation upon stimulation of the affected
eye, on average 33% (range 0 to 156%) of the average monocular activation in the
control group. Decreased activation was also seen for the unaffected eye (61% of
control values, range 3 to 133%). We conclude that fMRI with visual stimulation
is feasible in patients with optic neuritis and deserves future study.
PMID- 9633757
TI - Alpha tocopherol in CSF of subjects taking high-dose vitamin E in the DATATOP
study. Parkinson Study Group.
AB - Alpha-Tocopherol concentrations were determined in the CSF of patients with early
untreated Parkinson's disease receiving 2,000 IU vitamin E orally per day. After
treatment the concentrations increased significantly (p < 0.001) by 76+/-10
(SE)%. The net increases in CSF alpha-tocopherol concentrations after treatment
showed a significant positive correlation with the number of days of vitamin E
ingestion (p < 0.001). Thus, high-dose vitamin E treatment results in elevating
CSF vitamin E levels and possibly brain vitamin E levels.
PMID- 9633758
TI - Unilateral neglect: a common but heterogeneous syndrome.
AB - The neglect syndrome is a cluster of neurologic symptoms commonly found after
right hemisphere damage. This study investigates the degree of association
between the main components in a representative sample of 69 patients at 2 to 3
days poststroke. Despite evidence of statistically significant associations
between components, many dissociations were found, indicating that neglect is a
highly heterogeneous condition.
PMID- 9633759
TI - Confirmation of an association between a polymorphism in exon 3 of the low
density lipoprotein receptor-related protein gene and Alzheimer's disease.
AB - C766T, a polymorphism in exon 3 of the gene for the low-density lipoprotein
receptor-related protein (LRP), was found to be associated with late-onset
Alzheimer's disease (AD). We developed a PCR-restriction enzyme-based assay to
analyze this allele in 234 AD patients and 103 controls. We confirmed that the
LRP C766T polymorphism was in disequilibrium with AD--the C/C genotype was
present in 76% of AD patients and 60% of controls (p < 0.01); however, the LRP
polymorphism did not influence age at onset of AD.
PMID- 9633760
TI - Root stimulation studies in the evaluation of patients with motor neuron disease.
AB - Nerve root stimulation may be employed in patients with motor neuron disease
(MND) to rule out motor neuropathy with conduction block. The diagnostic utility
of these studies is unknown, in part because the range of amplitude changes
across nerve root segments in patients with active neuronal degeneration has not
been well studied. We reviewed root stimulation studies in 32 patients (59
nerves) with MND and found segmental amplitude reduction from 0 to 45%, a range
similar to values reported for normal subjects; there was no suggestion of
conduction block based on our usual criteria.
PMID- 9633761
TI - Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in
relapsing-remitting MS.
AB - To determine whether low-dose prednisone reduces flu-like symptoms at the
initiation of interferon beta 1-b (IFNbeta-1b), we studied 71 patients with
clinically definite, relapsing-remitting multiple sclerosis who were started on
IFNbeta-1b. Patients were randomized to receive prednisone plus paracetamol or
only paracetamol and were monitored for side effects. Systemic side effects were
minimal in the steroid group compared with the nonsteroid group during the first
15 days of treatment (p=0.005). At 3 months, both groups showed a similar
frequency of flu-like symptoms. No differences in local reaction between the two
groups were observed throughout the study.
PMID- 9633762
TI - Neuroacanthocytosis and aprebetalipoproteinemia.
AB - A 30-year-old woman presented with a progressive neurologic disorder
characterized by seizures, buccolingual dyskinesias, orofacial tics, choreiform
movements, atrophy, and areflexia. Investigations revealed normal lipid profile
except for aprebetalipoproteinemia. Phase-contrast and electron microscopy showed
35 to 40% acanthocytes. MRI and 18fluorodeoxyglucose-PET studies showed caudate
atrophy and hypometabolism. The phenotype of this patient is neuroacanthocytosis
and its association with aprebetalipoproteinemia may represent a new subentity of
the disorder.
PMID- 9633763
TI - Progressive facial hemiatrophy: abnormality of intracranial vasculature.
AB - Progressive facial hemiatrophy (PFH) or Parry-Romberg syndrome is associated with
ipsilateral brain lesions and neurologic symptoms. We describe a 35-year-old man
with PFH and frequent hemiplegic migraine. On cerebral angiography, reversible
vessel caliber changes were seen within the symptomatic hemisphere. An
abnormality of the intracranial vasculature may be present in some patients with
PFH and neurologic manifestations.
PMID- 9633764
TI - Petroclival meningioma presenting with pathological laughter.
PMID- 9633765
TI - Absence of HuD gene mutations in paraneoplastic small cell lung cancer tissue.
PMID- 9633766
TI - Matrix metalloproteinase 9 (gelatinase B) in cerebrospinal fluid of HTLV-1
infected patients with tropical spastic paraparesis.
PMID- 9633767
TI - Levodopa in human breast milk: clinical implications.
PMID- 9633768
TI - Acute transverse myelitis associated with tuberculin skin test (PPD).
PMID- 9633769
TI - Possible postherpetic neuralgia first occurring seven years after herpes zoster.
PMID- 9633770
TI - Wegener's granulomatosis presenting with bulbar palsy and bilateral jugular vein
compression.
PMID- 9633771
TI - Delayed diagnosis of Friedreich's ataxia due to coexisting recessive deaf/blind
syndrome.
PMID- 9633772
TI - Facial weakness in hereditary inclusion body myopathies.
PMID- 9633773
TI - Hypoglossal nerve palsy associated with deep cervical lymphadenopathy.
PMID- 9633774
TI - Are carotid endarterectomy complication rates being monitored?
PMID- 9633775
TI - Resolution of a brainstem abscess through antituberculosis therapy.
PMID- 9633776
TI - Medicare's resource-based relative value scale.
PMID- 9633777
TI - Anticytokine antibodies in beta-interferon-treated patients.
PMID- 9633778
TI - Anticytokine antibodies in beta-interferon-treated patients.
PMID- 9633779
TI - A 44-month clinical-brain MRI follow-up in a patient with B12 deficiency.
PMID- 9633780
TI - Acute intermittent porphyria.
PMID- 9633781
TI - Association of Ginkgo biloba with intracerebral hemorrhage.
PMID- 9633782
TI - Electrocerebral inactivity associated with obstructive sleep apnea.
PMID- 9633783
TI - Radiotherapy at tumor recurrence in primary CNS lymphoma.
PMID- 9633784
TI - Benign paroxysmal positioning vertigo.
PMID- 9633785
TI - Electrophysiologic findings in multifocal motor neuropathy.
PMID- 9633786
TI - Lack of association between blood pressure variability and left ventricular mass
in essential hypertension.
AB - Blood pressure (BP) variability could induce detrimental effects on left
ventricular (LV) structure in hypertension. We investigated the association
between short-term BP variability, assessed with 24-h noninvasive ambulatory BP
monitoring, and LV mass at echocardiography in 1822 untreated subjects (953 men,
869 women) with essential hypertension (EH). The standard deviation (SD) of
daytime and night-time systolic BP (SBP, r = 0.13/0.10; both P < .001), but not
of diastolic BP, showed a weak correlation with LV mass. Because the SD of
daytime SBP showed a direct association with average 24-h SBP (r = 0.27),
subjects were ranked into quartiles of the distribution of 24-h SBP. For each
quartile, the subjects with SD of daytime (and night-time) SBP below or above the
median were classified at low or high BP variability. In both genders, subjects
with high daytime SBP variability were older than those at low variability (both
P < .01). Within each quartile, LV mass did not differ between the groups at low
v those at high SBP variability. Overall, age-adjusted LV mass index was 115 and
115 g/m2 in men at low and high daytime SBP variability (P = .84), and 116 and
114 g/m2 in men at low and high nighttime SBP variability (P = .31). The
corresponding values in women were 98 and 99 g/m2 (P = .53) and 98 and 99 g/m2 (P
= .64). In conclusion, when the effects of age, gender, and average 24-h BP are
taken into account, short-term BP variability assessed with noninvasive
monitoring is unrelated to LV mass in subjects with EH.
PMID- 9633787
TI - Heart rate variability and baroreflex sensitivity in hypertensive subjects with
and without metabolic features of insulin resistance syndrome.
AB - Both abnormal autonomic control of heart rate, assessed by heart rate variability
(HRV) and baroreflex sensitivity (BRS), and insulin resistance syndrome are
common in hypertensive patients. It is not known, however, whether abnormalities
in HRV and BRS in hypertension are related to the insulin-resistance syndrome.
Therefore, we compared HRV and BRS in hypertensive subjects with and without
metabolic features of the insulin-resistance syndrome. HRV was analyzed using the
autoregressive method from a 45-min electrocardiographic recording (15 min lying,
sitting, and standing) and BRS using the Valsalva maneuver. The groups were
matched for age, sex, and antihypertensive medication, and age- and sex-matched
normotensive subjects served as a control group (n = 69 in each group). The
insulin-resistance syndrome was defined using the criteria of 1) hypertension
(blood pressure >160/90 mm Hg), 2) hypertriglyceridemia (fasting serum
triglycerides > or =2.0 mmol/L), and 3) hyperinsulinemia (fasting serum insulin >
or =12 mU/L). Standard deviation of RR intervals, total, very-low-, and low
frequency power of HRV were significantly lower in hypertensive subjects with
insulin-resistance syndrome compared to hypertensive subjects without the
syndrome and to normotensive controls (P < .001 for all), but the hypertensive
group without the syndrome did not differ from the normotensive group. High
frequency power of HRV (P < .01) and BRS (P < .05) were reduced in both
hypertensive groups compared to the normotensive group. In multiple regression
analysis, systolic blood pressure (P < .01) and serum triglyceride level (P <
.001) were independent predictors of reduced total power of HRV, but BRS was
related only to systolic blood pressure (P < .01). Thus, most of the
abnormalities in overall HRV seem to be confined to the subgroup of hypertensive
subjects with insulin-resistance syndrome, but baroreflex and respiratory
modulation of heart rate are impaired also in hypertensive subjects without
metabolic features of insulin-resistance syndrome.
PMID- 9633788
TI - Relationship between blood pressure variability and serum dehydroepiandrosterone
sulfate levels.
AB - Decreased diurnal blood pressure variability and low dehydroepiandrosterone
sulfate (DHEAS) levels are important predictors of cardiovascular morbidity and
mortality. The aim of the study was to determine the relationship between DHEAS
levels and diurnal blood pressure variability in normotensive subjects and in
patients with essential hypertension of both genders. An ambulatory blood
pressure monitor (ABPM), Meditech O2 device and radioimmunoassay were used for
ambulatory blood pressure monitoring and the determination of DHEAS levels,
respectively. A close correlation (P < .001) was found between the diurnal
indices and plasma DHEAS levels of the 387 subjects (86 normotensive and 301
hypertensive patients) participating in the study. Decreased plasma DHEAS levels
were associated in both genders, and in both normotensive and hypertensive
patients with significantly (P < .001) lower diurnal indices. There was a close
correlation (P < .001) between the age-related decrease in plasma DHEAS levels
and diurnal indices in both genders. Systolic and diastolic blood pressure
variability changed parallel to plasma DHEAS levels in both genders, whether
hypertension was present or not. Additional investigations are needed to find out
whether reduced DHEAS levels play a role in decreased diurnal indices or whether
both can be traced back to one and the same cause.
PMID- 9633789
TI - Blood pressure and heart rate in young thalassemia major patients.
AB - The analysis of blood pressure (BP) and heart rate (HR) variability is currently
used to investigate the mechanisms responsible for cardiovascular control;
therefore, we assessed whether an impairment of 24-h BP and HR profiles and
sympathovagal interaction modulating cardiovascular function was present in
patients with thalassemia major (TM) in preclinical phase of heart disease. Nine
beta-thalassemic patients 18 years old without clinical signs of cardiac failure
and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP
and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series
with four harmonics was used to describe the diurnal blood pressure profile. Mean
24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were
significantly lower in TM patients than in normal subjects (P < .05). A
significantly higher nighttime HR value was found in TM patients (P < .05). More
than 40% of the TM patients did not show a significant diurnal BP and HR rhythm.
In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was
significantly lower than in controls (P < .01). The night/day differences of
systolic BP, diastolic BP, and HR were significantly lower in TM patients than in
normals (P < .01). Furthermore, we performed power spectral analysis on short
term continuous finger BP and HR data in supine position and during passive head
up tilt. Total spectral power of systolic BP was significantly lower in patients
than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP
and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM
patients compared to controls (P < .05). High-frequency power of HR was
significantly higher in patients than controls (P < .05). The baroreflex gain
assessed by alpha-index was the same in supine position but was higher in TM
patients during passive tilt (P < .05). An inverse relationship between LF/HF
ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma
norepinephrine levels were significantly lower in thalassemics (P < .005). In
young TM patients in a preclinical stage of heart disease, these findings
demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term
variability of BP and HR, in particular in the LF range, showing a diminished
sympathetic activity.
PMID- 9633790
TI - Changes of plasma endothelin and growth factor levels, and of left ventricular
mass, after chronic AT1-receptor blockade in human hypertension.
AB - The stimulation of autocrine and paracrine factors such as basic fibroblast-
(bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth
promoting actions of angiotensin II. The aim of this study was to evaluate the
effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth
factors levels, and on left ventricular mass, in essential hypertension (EH). The
study population consisted of 16 patients with mild-moderate EH, and 25
normotensive controls. In the EH patients under basal conditions, and after 3 and
6 months of chronic therapy with Losartan 50 mg/day, we measured serum levels of
ET-1, bFGF and PDGF, and tumor necrosis factor (TNF). At the same time, all
patients underwent 24-h ambulatory blood pressure monitoring and an
echocardiographic evaluation to measure the thickness of the posterior wall (PWT)
of the left ventricle and of the interventricular septum (IVS). The healthy
controls underwent the same analyses, under basal conditions, at baseline and
after 3 and 6 months of observation. In the EH patients, after 3 months of AT1
receptor blockade bFGF was reduced from 13.6 +/- 0.7 to 10.9 +/- 0.7 pg/mL (P <
.004), and both TNF and PDGF were significantly decreased (P < .006 and P < .007,
respectively). After 6 months of therapy, ET-1 was significantly diminished in
comparison with baseline (6.9 +/- 0.8 v 5.5 +/- 0.1 fmol/mL; P < .05), and the
reduction in the levels of growth factors were even more significant than at 3
months of treatment. Both PWT and IVS were significantly changed after 6 months
of therapy with losartan after basal evaluation (P < .05, respectively). Systolic
and diastolic 24-h blood pressures declined significantly after 3 and 6 months of
therapy with losartan (P < .01, respectively). It seems likely that the
inhibition of the action of angiotensin II by the specific AT1-receptor blockade,
by reducing circulating levels of ET-1 and those of some growth factors, may
offer an advantage regarding the effect on hypertensive cardiovascular changes in
human hypertension.
PMID- 9633791
TI - Effect of chronic treatment with two different ET(A) selective endothelin
receptor antagonists on blood pressure and small artery structure of
deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
AB - Chronic treatment with a combined ET(A) and ET(B) endothelin receptor antagonist
blunts hypertension development and small artery hypertrophy in
deoxycorticosterone acetate (DOCA)-salt treated rats, in which endothelin-1 is
overexpressed in endothelial cells of blood vessels. To determine whether ET(A)
receptor antagonism played a predominant role in these findings, in this study
the effects of two orally active ET(A) selective endothelin receptor antagonists,
A-127722.5 and LU 135252, were evaluated on blood pressure and small artery
structure in DOCA-salt hypertensive rats. Rats received A-127722.5 (30 mg/kg/day)
or LU 135252 (50 mg/kg/day) in their drinking water since induction of
hypertension. Whereas three of 10 untreated DOCA-salt hypertensive rats died, in
the two treated groups none died and all appeared healthier. Systolic blood
pressure of treated DOCA-salt hypertensive rats, measured with the tail cuff
method, was lower than that of untreated DOCA-salt hypertensive rats by a mean of
20 mm Hg (P < .01) after 4 weeks of treatment with A-127722.5 and by 14 mm Hg (P
< .01) with LU 135252. Cardiac and aortic relative weights were unaffected by
treatment with either agent. Small arteries of the mesenteric, coronary, renal,
and femoral vasculature, examined under standardized conditions after mounting on
a wire myograph, were found to exhibit significant inward hypertrophic remodeling
in DOCA-salt hypertensive rats. DOCA-salt hypertensive rats treated with A
127722.5 had a significantly smaller media width and media-to-lumen ratio in the
four vascular beds examined, and rats treated with LU 135252 showed these
findings in mesenteric and renal small arteries. These results demonstrate that
chronic ET(A) selective antagonism induces similar effects to those of combined
ET(A)/ET(B) receptor antagonists in DOCA-salt hypertensive rats; namely, mild
reduction in development of hypertension and blunting of small artery
morphological changes, and also appears to improve survival. These results
suggest a role of ET(A) receptors in the endothelin dependent component of blood
pressure elevation in DOCA-salt hypertensive rats, and in the small artery
morphological changes present in this model of experimental hypertension.
PMID- 9633792
TI - Reduction of capillary permeability in the fructose-induced hypertensive rat.
AB - Impaired insulin transcapillary transport and the subsequent decrease in insulin
delivery to target organs have been suggested to play a role in insulin
resistance. These defects were studied in fructose-fed rats, an animal model with
insulin resistance. For this study, male Sprague-Dawley rats were fed with either
a 60% fructose enriched (F) or a standard chow diet (N) for a total of 2, 4, or 8
weeks. Capillary permeability to albumin was assessed at the end of each dietary
period by quantifying the extravasation of albumin-bound Evans blue (EB) dye in
different organs. Unanesthetized animals were injected with Evans blue dye (20
mg/kg) in the caudal vein 10 min before being killed and EB dye was extracted by
formamide from selected organs collected after exsanguination. As expected, rats
had an increase in blood pressure upon feeding with fructose at 4 and 8 weeks (F,
149 +/- 3 mm Hg; N, 139 +/- 3 mm Hg; P < .05). Using this technique, we showed a
56% and a 51% reduction in capillary permeability in skeletal muscles at 4 and 8
weeks of fructose feeding, respectively (4 weeks: N, 44.5 +/- 5.0 microg/g of dry
tissue; F, 19.8 +/- 4.2 microg/g of dry tissue; P < .01 and 8 weeks: N, 23.3 +/-
3.7 microg/g of dry tissue; F, 11.3 +/- 4.0 microg/g of dry tissue; P < .05).
Similar changes were observed at 4 weeks in the thoracic aorta (N, 82.8 +/- 8.8
microg/g of dry tissue; F, 53.0 +/- 5.1 microg/g of dry tissue; P < .02) and skin
(N, 36.0 +/- 5.3 microg of dry tissue; F, 15.0 +/- 2.3 microg/g of dry tissue; P
< .02) and at 8 weeks in the liver (N, 107.5 +/- 4.3 microg/g of dry tissue; F,
80.9 +/- 3.2 microg/g of dry tissue; P < .01). In conclusion, fructose feeding is
accompanied by a significant and selective reduction of Evans blue leakage
primarily in skeletal muscle and liver, and transiently in the skin and aorta,
consistent with a role for decreased tissue insulin delivery in insulin
resistance.
PMID- 9633793
TI - Renal uptake of circulating angiotensin II in Val5-angiotensin II infused rats is
mediated by AT1 receptor.
AB - Previous studies have demonstrated that augmentation of intrarenal angiotensin II
(ANG II) levels during ANG II induced hypertension involves both endogenous
formation and accumulation of circulating ANG II. The present work extends these
findings and determines whether accumulation of infused ANG II in the kidney
requires AT1 receptor activation by using Val5-ANG II as the infused peptide.
Male Sprague-Dawley rats were uninephrectomized and divided into three groups:
control (n = 6), Val5-ANG II (exogenous form) infused (n = 8), and Val5-ANG II
infused rats treated with losartan (n = 8). Val5-ANG II, which has the same
biological and immunoreactive properties as endogenous ANG II, was infused at 40
ng/min via an osmotic minipump implanted subcutaneously. By day 12, systolic
blood pressure (SBP) increased significantly in Val5-ANG II infused rats (197 +/-
7 mm Hg). As previously shown, the development of hypertension in ANG II infused
rats was prevented by losartan treatment. Blood and kidney samples were
harvested, subjected to HPLC to separate Val5-ANG II (exogenous) from Ile5-ANG II
(endogenous) and the fractions were measured by radioimmunoassay. In the Val5-ANG
II infused rats treated with losartan, total plasma ANG II levels were elevated
to a greater extent than in rats not treated with losartan (289 +/- 20 v 119 +/-
14 fmol/mL). However, losartan markedly decreased by 88% the enhancement of
intrarenal Val5-ANG II content that occurred in the rats infused with Val5-ANG II
alone. These results demonstrate that AT1 receptor blockade markedly reduces the
intrarenal uptake of circulating ANG II that occurs in ANG II induced
hypertension.
PMID- 9633794
TI - Inhibition by (-)-cicletanine of the vascular reactivity to angiotensin II and
vasopressin in isolated rat vessels.
AB - In pithed rats, the levorotatory (-)-enantiomer of cicletanine reduces the
pressor responses to angiotensin II (AII) and also, to a lesser extent, those to
arginine-vasopressin (AVP). Here we have attempted to characterize further these
inhibitory effects by studies of isolated perfused rat kidney and mesenteric
vascular beds. In the isolated rat kidney, (-)-cicletanine behaves as a
noncompetitive antagonist of AII- and AVP-receptor stimulation, with Ki values of
9.6 and 208 micromol/L respectively. In the isolated mesenteric vascular bed, (-)
cicletanine antagonized both AII dependent contractions with an inhibitory
concentration (IC50) of 54.0 +/- 20.5 micromol/L (n = 6), and AVP dependent
contractions with an IC50 of 31.6 +/- 5.0 micromol/L (n = 8). In conclusion, (-)
cicletanine antagonizes AII more effectively in rat kidney than in mesenteric
vascular beds. Moreover, in rat kidney vascular beds (-)-cicletanine is more
potent in blocking the pressor responses to AII than in blocking those to AVP. A
selective blockade of AII induced contractions in kidney vascular beds can be one
factor explaining both the greater antagonistic potency of (-)-cicletanine
against AII compared with AVP in pithed rats, and the renal protective properties
of cicletanine in both hypertensive and aged rats.
PMID- 9633795
TI - Increased tissue neutral endopeptidase 24.11 activity in spontaneously
hypertensive hamsters.
AB - The purpose of this study was to determine whether tissue neutral endopeptidase
(NEP) 24.11 activity, a membrane-bound metalloenzyme widely distributed in the
peripheral circulation that cleaves and inactivates vasodilator peptides, is
increased in spontaneously hypertensive hamsters relative to genetically/age
matched normotensive hamsters. Mean arterial pressure and heart rate were 163 +/-
11 mm Hg and 312 +/- 7 beats/min in spontaneously hypertensive hamsters and 99 +/
3 mm Hg and 302 +/- 10 beats/min in normotensive hamsters, respectively (mean +/
SEM). NEP 24.11 activity is significantly increased in the kidney, cheek pouch,
and spinotrapezius muscle, and significantly decreased in the heart and aorta of
spontaneously hypertensive hamsters relative to controls (P < .05). Lung and
brain NEP 24.11 activity is similar in both groups. Renal NEP 24.11 activity
increases and to a similar extent in spontaneously hypertensive and normotensive
hamsters as chloride anion concentration in the assay buffer is increased.
Substituting citrate for chloride anion significantly attenuates renal NEP 24.11
activity. Taken together, these data indicate that NEP 24.11 activity in
spontaneously hypertensive hamsters is increased in two organs that contribute
appreciably to peripheral vascular resistance, skeletal muscle, and kidney. We
suggest that the spontaneously hypertensive hamster is a suitable model to study
the role of skeletal muscle and renal NEP 24.11 in regulating vasomotor tone in
essential hypertension.
PMID- 9633796
TI - Effect of octreotide on 24-h blood pressure profile in acromegaly.
AB - The aim of the study was to investigate the effect of octreotide, a somatostatin
analog drug potentially able to inhibit growth hormone (GH), on the circadian
blood pressure profile in a group of patients with acromegaly. Ten patients with
GH-secreting pituitary adenoma were studied before and 6 months after treatment
with subcutaneous octreotide 0.2 to 0.6 mg/day. Twenty-four hour blood pressure
and heart rate were measured every 15 min at daytime (07:00 to 22:59) and every
30 min at nighttime (23:00 to 06:59) using a TM-2420 recorder. No correlation was
found between GH levels and 24-h blood pressure in baseline conditions. Untreated
patients had a significant nocturnal decrease of both systolic and diastolic
blood pressure (P < .01), and all showed a circadian systolic or diastolic blood
pressure rhythm. During octreotide treatment, 24 h as well as nighttime systolic
and diastolic blood pressures significantly increased (P < .05), whereas daytime
systolic and diastolic blood pressures did not change. Treated patients did not
have a nocturnal decline in both systolic and diastolic blood pressures (P = NS),
and eight lost their systolic or diastolic blood pressure rhythm. In conclusion,
blood pressure circadian rhythm seems to be maintained in acromegaly. Octreotide
treatment is associated with an increase of 24-h and nighttime blood pressure,
and with loss of circadian blood pressure rhythm. Splanchnic vasoconstriction by
this drug, shifting blood to peripheral vessels, may explain this phenomenon.
PMID- 9633797
TI - Comparison of effects of antihypertensive drugs on heart rate: changes from
baseline by baseline group and over time. Department of Veterans Affairs
Cooperative Study Group on Antihypertensive Agents.
AB - Baseline heart rate is becoming recognized as a predictor of cardiovascular risk.
Various antihypertensive drugs have differing effects on heart rate. A randomized
controlled clinical trial of 1292 ambulatory men with stage 1 or 2 hypertension
was conducted in 15 Veterans Affairs medical centers. Patients were treated with
hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or
placebo for up to 2 years. Heart rates were measured at baseline, the end of
titration, 1 year, and 2 years. Data were also stratified by baseline heart rate.
A subset of patients had heart rate also determined by electrocardiogram. All
drugs except prazosin reduced heart rate from baseline; additional small
decreases were obtained over time with hydrochlorothiazide and placebo. The
decrease initially achieved with clonidine was attenuated over time. The overall
reduction in heart rate was greatest for atenolol (-12.2 beats/min) and least for
prazosin (+3.8 beats/min). Only atenolol effected a further reduction of heart
rate for patients whose baseline rate was < or =65 beats/min. All drugs reduced
heart rate when the baseline was > or =85 beats/min. Data derived by
electrocardiogram yielded similar results. The drugs used in this study differ in
their ability to reduce heart rate, sustain that reduction over time, and to
change heart rate in groups with high or low rates at baseline. The importance of
these comparative changes as independent cardiac risk factor variables remains to
be determined.
PMID- 9633798
TI - No relevant seasonal influences on office and ambulatory blood pressure: data
from a study in borderline hypertensive primary care patients.
AB - Our objective was to study seasonal influences on office and ambulatory blood
pressure. We therefore designed a prospective 7-month study of 47 borderline
hypertensive patients in a primary care setting. We used no interventions. Our
main outcome measures were the differences between summer and winter office and
ambulatory blood pressures and 95% confidence intervals. Results showed that
winter minus summer differences ranged from 0 to 3 mm Hg. Only one significant
difference was found: ambulatory systolic daytime pressure was significantly
higher (3 mm Hg) in winter than in summer. Our results do not confirm the data of
earlier studies in hypertensives. In view of the small and clinically irrelevant
winter-summer differences, it seems unnecessary to modify antihypertensive
treatment of borderline hypertensives according to the season.
PMID- 9633799
TI - How reliable is nighttime blood pressure dipping?
AB - This report examines the reliability of nighttime blood pressure dipping. Twenty
one individuals were studied twice with ambulatory blood pressure monitoring. On
one occasion they were studied as outpatients, and on the other as inpatients on
a clinical research ward. Blood pressure monitoring revealed the expected dip in
blood pressure at nighttime. However, there was little test-retest reliability
across the two settings. The test-retest correlations for the dip in blood
pressure across the two settings were nonsignificant for systolic, diastolic, and
mean arterial blood pressure. Caution is advised before diagnosing dipping or
nondipping on the basis of one 24-h ambulatory blood pressure recording.
PMID- 9633800
TI - Training students in education of the hypertensive patient: enhanced performance
after a simulated patient instructor (SPI)-based exercise.
AB - The process whereby a physician explains to the ill patient what has gone wrong
and what can be done about it can be taught and evaluated by simulated patients
(SPIs). This study was designed to determine whether a training experience in
educating a diabetic SPI improves subsequent performance with a hypertensive SPI.
Competence in educating a hypertensive SPI by students who had no prior training
experience (n = 26) was compared to that of an experimental group (n = 20) that
had a prior training session. Performance was assessed with a counseling skills
scale and a case-specific content checklist (1 = poor to 5 = excellent). Students
in the experimental group performed better than controls in both counseling
skills (4.46 v 3.86, P < .01) and completeness of coverage of content (3.28 v
2.65, P < .01). Students in both groups focused more on clinical features and
treatment than on laboratory testing and follow-up. The ability to counsel
"patients" with hypertension can be enhanced by a prior learning experience with
a diabetic SPI. Clinical application of knowledge about hypertension can be
assessed by SPIs.
PMID- 9633801
TI - Hemodynamic differences between metoprolol and carvedilol in hypertensive
patients.
AB - Resting hemodynamics were measured before, at 2 and 24 h after the first dose,
and after 4 weeks of monotherapy with either metoprolol or carvedilol in a
randomized single-blind study. We analyzed results from 24 hypertensive patients
(30-68 years of age) with adequate blood-pressure lowering on monotherapy.
Acutely, both drugs lowered systolic blood pressure and heart rate. Whereas
metoprolol reduced cardiac output and increased both systemic and femoral artery
resistance, carvedilol did not alter cardiac output but led to reductions in the
systemic and regional resistances. After 4 weeks of therapy, cardiac output
remained reduced and vascular resistances increased in the metoprolol group,
whereas in carvedilol patients cardiac output continued to be unchanged and the
trend for vascular resistances to be decreased persisted. Acutely and chronically
the differences in the hemodynamic effects of the two medications were
statistically significant. The study results indicate that carvedilol's
vasodilatory action is not subject to tolerance development. Chronic afterload
reduction associated with the decrease in systemic vascular resistance may lead
to additional savings in myocardial oxygen consumption, a beneficial feature
particularly in those patients with concomitant ischemic heart disease. It may
also have a favorable influence on concentric cardiac hypertrophy and changes in
the walls of arteriolar resistance vessels.
PMID- 9633802
TI - Cost-minimization and the number needed to treat in uncomplicated hypertension.
AB - The goal of this study was to compare the direct costs associated with the
prescription of thiazide diuretics, beta-receptor blockers (beta-blockers),
angiotensin converting enzyme inhibitors (ACEI), a-receptor blockers (alpha
blockers), and calcium channel blockers (CCB) for the prevention of stroke,
myocardial infarction (MI) and premature death in uncomplicated hypertension. We
performed a cost-minimization analysis based on numbers-needed-to-treat (NNT)
derived from the metaanalysis of 15 major clinical trials of hypertension
treatment, and the average wholesale prices of both the most commonly prescribed
and the least expensive drugs in each class. The inclusion criteria for clinical
trials were that they be randomized, controlled trials of drug therapy of
uncomplicated mild-to-moderate hypertension with stroke, MI, or death as
endpoints. The wholesale drug costs and the total direct outpatient treatment
costs to prevent a stroke, MI or death among middle-aged and elderly
hypertensives were our outcome measures. The estimated wholesale drug acquisition
cost to prevent one major event (MI or stroke or death) ranged from $4730 to
$346,236 among middle-aged patients, and from $1595 to $116,754 in the elderly;
generic diuretic or beta-blocker therapy was more economical than treatment with
an ACEI, alpha-blocker, or CCB. The associated 5-year NNT was 86 for middle-aged
patients and 29 for elderly patients. Diuretic therapy remained more cost
effective even under the unlikely assumption that the newer drugs were 50% more
effective than diuretics at preventing these major events. The costs associated
with potassium supplementation did not eliminate the advantage of diuretics.
Treatment costs to prevent major hypertensive complications are much lower with
diuretics and beta-blockers than with ACEI, CCB, or alpha-blockers, especially in
middle-aged patients.
PMID- 9633803
TI - Differential effects of central and peripheral nerves on macrophages and
microglia.
AB - The poor ability of injured central nervous system (CNS) axons to regenerate has
been correlated, at least partially, with a limited and suppressed postinjury
inflammatory response. A key cell type in the inflammatory process is the
macrophage, which can respond in various ways, depending on the conditions of
stimulation. The aim of this study is to compare the activities of macrophages or
microglia when encountering CNS and peripheral nervous systems (PNS), on the
assumption that nerve-related differences in the inflammatory response may have
implications for tissue repair and thus for nerve regeneration. Phagocytic
activity of macrophages or of isolated brain-derived microglia was enhanced upon
their exposure to sciatic (PNS) nerve segments, but inhibited by exposure to
optic (CNS) nerve segments. Similarly, nitric oxide production by macrophages or
microglia was induced by sciatic nerve segments but not by optic nerve segments.
The previously demonstrated presence of a resident inhibitory activity in CNS
nerve, could account, at least in part, for the inhibited phagocytic activity of
blood-borne macrophages in CNS nerve as well as of microglia resident in the
brain. It seems that the CNS microglia are reversibly immunosuppressed by the CNS
environment, at least with respect to the activities examined here. It also
appears from this study that the weak induction of early healing-related
activities of macrophages/microglia in the environment of CNS might explain the
subsequent failure of this environment to acquire growth-supportive properties in
temporal and spatial synchrony with the needs of regrowing axons.
PMID- 9633804
TI - Visualization of mitotic radial glial lineage cells in the developing rat brain
by Cdc2 kinase-phosphorylated vimentin.
AB - Although accumulating data reveal patterns of proliferation, migration, and
differentiation of neuronal lineage cells in the developing brain, gliogenesis in
the brain has not been well elucidated. In the rat brain, vimentin is selectively
expressed in radial glia and in their progeny, not in oligodendrocytes or neurons
from embryonic day 15 (E15) until postnatal day 15 (P15). Here we examined
mitotic radial glial lineage cells in the rat brain E17-P7, using the monoclonal
antibody 4A4, which recognizes vimentin phosphorylated by a mitosis-specific
kinase, cdc2 kinase. In the neocortex, mainly radial glia in the ventricular
zone, but not their progeny, underwent cell division. In contrast, not only
radial glia but also various types of radial glial progeny including Bergmann
glia continued to proliferate in the cerebellum. Radial glia in the neocortex
divided horizontally, obliquely, and vertically against the ventricular surface.
The percentage of the vertical division increased with progress in the stage of
development, concurrently with the decrease of the population of horizontal
divisions. Thus, the monoclonal antibody 4A4 provides an useful tool to label
mitotic glia in the developing brain and revealed different patterns of
gliogenesis in the neocortex and cerebellum. A possibility is discussed that the
dynamics of mitotic orientation observed here may be related to the change of the
pattern of gliogenesis during development.
PMID- 9633805
TI - Glial cells have heart: rH1 Na+ channel mRNA and protein in spinal cord
astrocytes.
AB - Astrocytes in vitro express several distinct voltage-sensitive sodium currents,
including tetrodotoxin (TTX)-resistant in non-stellate astrocytes and TTX
sensitive currents in stellate astrocytes. However, the molecular identity of the
underlying channels, and the mechanisms that regulate their expression, have yet
to be identified. Since spinal cord astrocytes in vitro express sodium currents
that are nearly ten-fold greater that those of astrocytes derived from other
regions, we used reverse transcription polymerase chain reaction (RT-PCR), in
situ hybridization, and immunocytochemistry to search for a sodium channel mRNA
and protein corresponding to a TTX-resistant channel in these cells. RT-PCR did
not detect transcripts for SNS, which is known to encode a TTX-resistant current
in dorsal root ganglion neurons. However, RT-PCR demonstrated the presence of rH1
mRNA in cultured spinal cord astrocytes derived from postnatal day 0 (P0) Sprague
Dawley rats at 7 days in vitro and in also intact spinal cords of P0 and P7 rats.
Hybridization signal for rH1 mRNA was detected by in situ hybridization
cytochemistry in most non-stellate and, at varying levels, in stellate astrocytes
in these cultures. Immunocytochemical studies, utilizing a polyclonal antibody (R
12) generated against a conserved polypeptide sequence of sodium channels,
demonstrated sodium channel immunoreactivity in non-stellate and stellate
astrocytes in these cultures. Spinal cord cultures reacted with a rH1-specific
polyclonal antibody also showed rH1 immunostaining in non-stellate and stellate
astrocytes, although the intensity of the rH1 immunoreactivity in both astrocyte
morphologies was attenuated compared to that observed with the R-12 generic
sodium channel antibody. The presence of rH1 mRNA and protein in non-stellate
astrocytes in vitro provides a possible correlate for the TTX-resistant current
that has been recorded in these cells. Since TTX-resistant current is not present
in stellate astrocytes, the presence of rH1 mRNA and protein in these cells
suggests, in addition, that post-translational mechanisms participate in the
control of sodium channel expression in these cells.
PMID- 9633806
TI - Spermine/spermidine is expressed by retinal glial (Muller) cells and controls
distinct K+ channels of their membrane.
AB - There is recent evidence that polyamines such as spermine (spm) and spermidine
(spd) may act as endogenous modulators of the activity of inwardly rectifying K+
channels. This type of K+ channels is abundantly expressed by retinal glial
(Muller) cells where they are involved in important glial cell functions such as
the clearance of excess extracellular K+ ions. This prompted us to study the
following questions, i) do mammalian Muller cells contain endogenous spm/spd?;
ii) do Muller cells possess the enzymes (e.g., ornithine decarboxylase, ODC)
necessary to produce spm/spd?; and iii) does application of exogenous spm/spd
exert specific effects onto inwardly rectifying K+ channels of Muller cells?
Immunocytochemical studies were performed on histological sections of guinea-pig,
rabbit, porcine, and human retinae, and on enzymatically dissociated Muller
cells. Whole-cell and patch-clamp recordings were performed on enzymatically
dissociated porcine and guinea-pig Muller cells. All above-mentioned questions
could be answered with "yes." Specifically, the majority of Muller cells were
labeled with antibodies directed to spm/spd, both within retinal sections and
enzymatically isolated from retinal tissue. Muller cells in normal retinae
express low levels of ODC but increase this expression markedly in cases of
retinal pathology such as experimental epiretinal melanoma. Externally applied
polyamines (1 mM) reduce (predominantly inward) whole-cell K+ currents, with the
efficacies being spm > spd > put. If applied at the inside of membrane patches,
spm (1 mM) blocks completely the outward currents through inwardly rectifying K+
channels but fails to affect the activity of large conductance, Ca2+-activated K+
channels. It is concluded that Muller cells contain endogenous channel-active
polyamines, the synthesis of which may be up-regulated in pathological
situations, and which may be involved in the control of both glial function and
cell proliferation.
PMID- 9633807
TI - Glial cell responses, complement, and clusterin in the central nervous system
following dorsal root transection.
AB - We have examined the glial cell response, the possible expression of compounds
associated with the complement cascade, including the putative complement
inhibitor clusterin, and their cellular association during Wallerian degeneration
in the central nervous system. Examination of the proliferation pattern revealed
an overall greater mitotic activity after rhizotomy, an exclusive involvement of
microglia in this proliferation after peripheral nerve injury, but, in addition,
a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with
the phagocytic cell marker ED1 gradually became very prominent after rhizotomy,
possibly reflecting a response to the extensive nerve fiber disintegration.
Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG)
deposition or complement expression in the spinal cord dorsal horn, dorsal
funiculus, or gracile nucleus. This is in marked contrast to the situation after
peripheral nerve injury, which appears to activate the entire complement cascade
in the vicinity of the central sensory processes. Clusterin, a multifunctional
protein with complement inhibitory effects, was markedly upregulated in the
dorsal funiculus in astrocytes. In addition, there was an intense induction of
clusterin expression in the degenerating white matter in oligodendrocytes,
possibly reflecting a degeneration process in these cells. The findings suggest
that 1) complement expression by microglial cells is intimately associated with
IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central
fibers, undergo changes which induce such deposition; and 3) clusterin is not
related to complement expression following neuronal injury but participates in
regulating the state of oligodendrocytes during Wallerian degeneration.
PMID- 9633808
TI - Lesion-induced changes in the expression of ciliary neurotrophic factor and its
receptor in rat optic nerve.
AB - There is evidence that ciliary neurotrophic factor (CNTF) is involved in reactive
changes following lesions of the nervous system. To investigate, whether
differences in the regulation of CNTF and CNTF receptor alpha (CNTFRalpha)
contribute to the differences in PNS and CNS responses to injury, we have studied
their expression on the mRNA and protein level in the rat optic nerve following a
crush lesion to compare them with the situation in peripheral nerve. Seven days
after the lesion, CNTF mRNA and protein levels were markedly decreased at the
lesion site, concommitant with the disappearance of GFAP- and CNTF-immunopositive
astrocytes. CNTF levels in proximal and distal parts were less affected. This was
in contrast to the situation in the PNS, where CNTF was downregulated at and
distal to the lesion site. Different from other CNS regions, optic nerve
astrocytes expressed CNTFRalpha mRNA under normal conditions. Following lesion,
CNTFRalpha was reduced substantially only in distal and proximal parts of the
optic nerve but continued to be expressed at high levels at the lesion site,
suggesting that GFAP-negative, CNTF-responsive cells are present there. Our
results suggest that differences in lesion-induced changes in the optic and
sciatic nerve reflect differences in the response to injury of astrocytes and
Schwann cells. In the light of the known actions of CNTF in inducing
astrogliosis, the expression pattern observed in the optic nerve indicates that
CNTF and CNTFRalpha are involved in glial scar formation in the lesion area.
PMID- 9633809
TI - Relationship of microglial and astrocytic activation to disease onset and
progression in a transgenic model of familial ALS.
AB - Transgenic mice that highly over-express a mutated human CuZn superoxide
dismutase (SOD1) gene [gly93-->ala; TgN(SOD1-G93A)G1H line] found in some
patients with familial ALS (FALS) have been shown to develop motor neuron disease
that is characterized by motor neuron loss in the lumbar and cervical spinal
regions and a progressive loss of motor activity. The mutant Cu,Zn SOD exhibits
essentially normal SOD activity but also generates toxic oxygen radicals as a
result of an enhancement of a normally minor peroxidase reaction. Consequently,
lipid and protein oxidative damage to the spinal motor neurons occurs and is
associated with disease onset and progression. In the present study, we
investigated the time course of microglial (major histocompatibility-II antigen
immunoreactivity) and astrocytic (glial fibrillary acidic protein
immunoreactivity) activation in relation to the course of motor neuron disease in
the TgN(SOD1-G93A)G1H FALS mice. Four ages were investigated: 30 days (pre-motor
neuron pathology and clinical disease); 60 days (after initiation of pathology,
but pre-disease); 100 days (approximately 50% loss of motor neurons and
function); and 120 days (near complete hindlimb paralysis). Compared to non
transgenic littermates, the TgN(SOD1-G93A)G1H mice showed significantly increased
numbers of activated astrocytes (P < 0.01) at 100 days of age in both the
cervical and lumbar spinal cord regions. However, at 120 days of age, the
activation lost statistical significance. In contrast, microglial activation was
significantly increased several-fold at both 100 and 120 days. We hypothesize
that astrocytic activation may exert a trophic influence on the motor neurons
that is insufficiently maintained late in the course of the disease. On the other
hand, the sustained, intense microglial activation may conceivably contribute to
the oxidative stress and damage involved in the disease process. If true, then
agents which inhibit microglia may help to limit disease progression.
PMID- 9633810
TI - E587 antigen is upregulated by goldfish oligodendrocytes after optic nerve lesion
and supports retinal axon regeneration.
AB - The properties of glial cells in lesioned nerves contribute quite substantially
to success or failure of axon regeneration in the CNS. Goldfish retinal axons
regenerate after optic nerve lesion (ONS) and express the L1-like cell adhesion
protein E587 antigen on their surfaces. Goldfish oligodendrocytes in vitro also
produce E587 antigen and promote growth of both fish and rat retinal axons. To
determine whether glial cells in vivo synthesize E587 antigen, in situ
hybridizations with E587 antisense cRNA probes and light- and electron
microscopic E587 immunostainings were carried out. After lesion, the goldfish
optic nerve/tract contained glial cells expressing E587 mRNA, which were few in
number at 6 days after ONS, increased over the following week and declined in
number thereafter. Also, E587-immunopositive elongated cells with ultrastructural
characteristics of oligodendrocytes were found. Thus, glial cells synthesize E587
antigen in spatiotemporal correlation with retinal axon regeneration. To
determine the functional contribution of E587 antigen, axon-oligodendrocyte
interactions were monitored in co-culture assays in the presence of Fab fragments
of a polyclonal E587 antiserum. E587 Fabs in axon-glia co-cultures prevented the
normal tight adhesion of goldfish retinal growth cones to oligodendrocytes and
blocked the preferential growth of fish and rat retinal axons on the
oligodendrocyte surfaces. The ability of glia in the goldfish visual pathway to
upregulate the expression of E587 antigen and the growth supportive effect of
oligodendrocyte-associated E587 antigen in vitro suggests that this L1-like
adhesion protein promotes retinal axon regeneration in the goldfish CNS.
PMID- 9633811
TI - [U-13C] aspartate metabolism in cultured cortical astrocytes and cerebellar
granule neurons studied by NMR spectroscopy.
AB - The metabolism of [U-13C]aspartate was studied in cultured cortical astrocytes
and cerebellar granule neurons in the presence of glucose and during inhibition
of glycolysis. Redissolved, lyophilized cell extracts and incubation media were
analyzed by 13C nuclear magnetic resonance spectroscopy for the determination of
metabolites labeled from aspartate. Uniformly labeled lactate was prominent in
control media of astrocytes and cerebellar granule neurons. In both cell types,
aspartate entered the tricarboxylic acid (TCA) cycle, as shown by labeling
patterns in glutamate and, in astrocytes, in glutamine. From the complex labeling
patterns in aspartate in astrocytic perchloric acid extracts it was clear that
acetylcoenzyme A (acetyl-CoA) derived from aspartate via oxaloacetate and
pyruvate could enter the TCA cycle. Such "recycling," however, could not be
detected in cerebellar granule neurons. Inhibition of glycolysis reduced
aspartate uptake and metabolism in both cell types. Most notably, lactate derived
from aspartate showed a large reduction, and in astrocytes, incorporation of
labeled acetyl-CoA into the TCA cycle was significantly reduced. Thus, astrocytes
and cerebellar granule neurons differ in their handling of aspartate.
Furthermore, inhibition of glycolysis clearly affected aspartate metabolism by
such cells.
PMID- 9633812
TI - Oligodendroglial reaction following spinal cord injury in rat: transient
upregulation of MBP mRNA.
AB - The reaction of oligodendrocytes in response to traumatic injury of the CNS are
poorly understood. In the present report we studied changes in the expression of
a major constituent of CNS myelin, myelin basic protein (MBP), by
immunohistochemistry and in situ hybridization from 6 h up to 2 weeks following
partial transection of the spinal cord in adult rats. MBP immunohistochemistry
showed degeneration of myelin at the lesion center and signs of myelin breakdown
in necrotic foci in the dorsal and ventral funiculi proximal and distal to the
lesion. In situ hybridization revealed that mRNA for MBP was downregulated at the
local lesion site within the first day following injury, probably reflecting
oligodendrocytes to undergo cell death. From 2 days on, however, MBP mRNA was
conspicuously upregulated at the border of the lesion area. This "reactive"
response of surviving oligodendrocytes, as indicated by increased levels of MBP
mRNA, peaked around 8 days. At this time, oligodendrocytes displaying strong MBP
in situ signal formed stripe-like structures which were oriented radially toward
the lesion center and arranged in parallel to neurofilament-positive axons. At
around 2 weeks post-injury, MBP mRNA at the border of the lesion area was again
downregulated to levels comparable to uninjured controls. These results show that
traumatic injury of the spinal cord induces a "reactive" response of surviving
oligodendrocytes adjacent to lesion sites. This response might represent an
important component of local repair mechanisms.
PMID- 9633813
TI - Proof of "disease causing" mutation.
PMID- 9633814
TI - Pooled analysis of p53 mutations in hematological malignancies.
AB - A computerized database is described that contains information about 507
mutations in the p53 gene of hematologic tumors and corresponding cell lines.
Analysis of these mutations indicated the following findings: First, mutational
spectrum analysis in these tumors was found to be similar to the pattern found
for other solid tumors. However, when the patterns of base substitutions were
examined separately according to the types of hematologic malignancies, followed
by subgroup analysis, notable differences (in some cases of statistical
significance) emerged. Second, mutational pattern analysis indicates that about
48% of base substitutions in hematologic tumors are suspected to be associated
with carcinogen exposure. Third, deletions and insertions are localized mainly to
exons 5-8 and repeated DNA sequences. However, the unusual profile of variations
in frequency within each type of tumor suggests that, in addition to endogenous
damage to template DNA, there is the factor of exposure to environmental physical
and chemical carcinogens/mutagens. Fourth, p53 protein alterations analysis
indicate that most of the changes in the amino acids are "semiconservative,"
presumably in order to avoid disrupting the structure of the p53 monomer.
Consistent with this notion, structural mutations are more conservative than the
binding mutations. Finally, molecular mechanisms that lead to p53 mutations,
etiological factors that play a role in their formation, and the
pathophysiological significance of consequent p53 protein alterations are
discussed.
PMID- 9633815
TI - Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia
type 1 patients in northwestern Europe and Mediterranean countries.
AB - Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a
deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the
molecular heterogeneity of tyrosinemia, the geographic distribution and the
genotype-phenotype relationship, we have analyzed the FAH genotype of 25 HT1
patients. Mutation screening was performed by PCR amplification of exons 1-14 of
the FAH gene, followed by SSCP analysis and direct sequencing of the amplified
exons. Fourteen different mutations were found, of which seven were novel, viz.
three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides
causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g
t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g
a) were frequently found in countries around the Mediterranean and northwestern
Europe, respectively. No clear correlation between the genotype and the three
major HT1 subtypes could be established.
PMID- 9633816
TI - Molecular diagnosis of McArdle disease: revised genomic structure of the
myophosphorylase gene and identification of a novel mutation.
AB - McArdle disease is a rare autosomal recessive disorder of the muscle glycogen
metabolism caused by mutations in the muscle glycogen phosphorylase gene. Until
now, a total number of 11 different mutations in the coding region or splice
sites of the myophosphorylase gene have been identified. In contrast to a wealth
of data on the RNA and protein level, little information is available on the
genomic sequence of the corresponding gene. To facilitate molecular diagnosis of
McArdle disease, we reinvestigated the genomic structure of the myophosphorylase
gene and sequenced about 9.8 kilobases (kb) on the genomic level. By choosing 14
intronic primer pairs, we were able to amplify the complete human coding sequence
as well as the adjacent splice sites of the 20 exons. Direct sequencing of the
amplification products of a consanguineous Turkish family with typical McArdle
disease revealed a novel single base pair deletion in exon 18, which predicts a
frameshift and a premature termination of the protein. In summary, we established
a system for molecular diagnosis of McArdle disease based on a revised genomic
structure of the myophosphorylase gene and demonstrated its feasibility by
identification of a novel mutation.
PMID- 9633817
TI - Deletion analysis of Bulgarian SMA families.
AB - All three types of autosomal recessive spinal muscular atrophy map to chromosome
region 5q13. Recent reports suggest that they are associated with deletions of
two adjacent genes: SMN and NAIP. Here we report the first deletion analysis of
Bulgarian SMA families. Homozygous deletion of exons 7 and 8 of the SMN gene were
found in 85% of our patients, but the NAIP gene (exons 5 and 6) was deleted in
only 26% of patients. To our knowledge, these frequencies are some of the lowest
reported so far. The NAIP gene was deleted predominantly in severely affected
patients (type I), while in the group with milder types SMA only deletions of the
SMN gene were detected. Our phenotype-genotype correlation study confirmed that
larger deletions are associated with more severe clinical course. The Bulgarian
data support the thesis that the telomeric SMN gene could play a major role in
determining SMA, while the NAIP or the centromeric SMN copy have a modifying
effect on the phenotype.
PMID- 9633818
TI - Mutations of the cationic trypsinogen in hereditary pancreatitis.
AB - Hereditary pancreatitis (OMIM 167800) is thought to be associated with a mutation
of the exon 3 of cationic trypsinogen (Nature Genet (1996): 14:141-145). This
paper reports sequence data of two independent families suffering from this
disease. PCR amplificates from leukocyte or buccal swab DNA showed no mutation of
exon 3 of cationic trypsinogen. Instead, in exon 2, an A-to-T tranversion was
found that led to the substitution of Asn by Ile in the sixth amino acid of the
active trypsin. In exons 4 and 5, silent mutations were found. In the other
expressed trypsinogens, several homozygous alterations not associated to
hereditary pancreatitis were identified. As a model of pathogenesis, we
hypothesize that mutation of trypsinogen in exon 2 could lead to premature
cleavage of the activation peptide of trypsinogen or to altered intracellular
transport.
PMID- 9633819
TI - Different missense mutations in histidine-108 of lysosomal acid lipase cause
cholesteryl ester storage disease in unrelated compound heterozygous and
hemizygous individuals.
AB - Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both
autosomal recessive disorders associated with reduced activity of lysosomal acid
lipase (LAL), that leads to the tissue accumulation of cholesteryl esters in
endosomes and lysosomes. WD is caused by genetic defects of LAL that leave no
residual enzymatic activity, while in CESD patients a residual LAL activity can
be identified. We have analyzed the LAL cDNA in three CESD patients from two
nonrelated families and identified the mutations responsible for the disease. The
associated genetic defects characterized revealed compound heterozygosity for a
splice defect leading to skipping of exon 8, due to a G-->A transition at
position -1 of the exon 8 splice donor site, and a point mutation leading to a
Hisl08Pro change (CAT-->CCT) in two patients (siblings) with mild CESD phenotype.
A further CESD patient was hemizygous for a His108-->Arg missense mutation (CAT-
>CGT) in combination with a partial deletion of the LAL gene and was affected
more severely. Expression of the LAL enzymes with the His108-->Pro and His108-
>Arg mutation in insect cells revealed residual enzymatic activities of 4.6%
versus 2.7%, respectively, compared with controls. Therefore, His108 seems to
play a crucial role in folding or catalytic activity of the lysosomal acid
lipase. This is the first description of two different, naturally occurring
mutations involving the same amino acid residue in the lysosomal acid lipase in
unrelated CESD patients. Moreover, our results demonstrate that the variable
manifestation of CESD can be explained by mutation-dependent, variable
inactivation of the LAL enzyme.
PMID- 9633820
TI - Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age
at onset of diabetes and deafness.
AB - The mitochondrial mutation A3243G has been shown to be associated with a syndrome
of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based
sequencing method we have investigated the relation between the proportion of
mutant mitochondrial genomes and the time of disease onset among members of three
families where the mutation segregates. A striking association was observed
between the level of heteroplasmy and time of onset of disease, particularly
hearing loss. Accordingly, this syndrome shares features of diseases caused by
dynamic mutations in that variable transmission of the level of heteroplasmy
between generations influences disease severity.
PMID- 9633821
TI - Spectrum of mutations in Finnish patients with Charcot-Marie-Tooth disease and
related neuropathies.
AB - Our patient material included families and sporadic patients of Finnish origin
with the diagnosis of Charcot-Marie-Tooth (CMT) disease types 1 and 2, Dejerine
Sottas syndrome (DSS), and hereditary neuropathy with liability to pressure
palsies (HNPP). We screened for mutations in the peripheral myelin protein genes
connexin 32 (Cx32), myelin protein zero (P0) and peripheral myelin protein 22
(PMP22) by direct sequencing. All patients chosen for mutation screening were
negative for the 1.5 Mb duplication/deletion at 17p11.2-p12. Eleven Cx32
mutations were found in 12 families, six with a CMT2 diagnosis, three with a CMT1
diagnosis and three with unclassified CMT. The total number of patients in these
12 CMTX families was 61, giving a minimum prevalence of 1.2/100,000 for CMTX in
Finland. Four of the mutations, Pro58Arg, Pro172Leu, Asn175Asp and Leu204Phe,
have not been previously reported. One male patient with an early onset CMT had a
double Cx32 mutation, Arg22Gln and Val63Ile. The double de novo mutation was
found to be of maternal grandpaternal origin. In the P0 gene a Ser78Leu mutation
was found in one family with severe CMT1 and a de novo Tyr82Cys mutation was
found in one DSS patient. Both mutations have been previously reported in other
CMT1 families. A novel PMP22 mutation, deletion of Phe84, was found in one
sporadic DSS patient. Our mutation screening results show the necessity of
molecular diagnosis, in addition to clinical and electrophysiological evaluation,
for proper subtyping of the disease and for accurate genetic counseling.
PMID- 9633823
TI - Calcium mediated proteolysis enhances calcium release in skinned L6 myotubes.
AB - The mechanism for calcium (Ca2+) release in heart and skeletal muscle during
excitation-contraction coupling is currently unknown. A widely held hypothesis is
that a small amount of Ca2+ enters the cell and elicits a larger intracellular
release of Ca2+ from the sarcoplasmic reticulum (SR), termed "Ca2+-induced Ca2+
release" (CICR). In addition to its role in excitation-contraction coupling, Ca2+
is also known to activate the cysteine protease calpain, which has been recently
found to specifically cleave the ryanodine receptor in vitro. The authors
investigated the question of whether Ca2+ sensitive protease activation could
account for an apparent CICR. The authors first reproduced the phenomenon of CICR
using detergent treated L6 myotubes ("skinned cells"). Leupeptin, a cysteine
protease inhibitor, reduced the initial velocity and extent of Ca2+ release from
the SR; a similar result was obtained when skinned cells were treated with
iodoacetate, a sulfhydryl alkylating agent. Dithiothreitol enhanced both the rate
and extent of Ca2+ release. Caffeine-induced Ca2+-release was unaffected by the
thiol protease inhibitors or activators. This suggests that a cysteine protease
may be responsible, in part, for CICR in vitro. The authors also found that
vesicles exposed to Ca2+ to induce CICR were unable to fully reaccumulate Ca2+ a
second time. Yet, when caffeine released comparable amounts of Ca2+, the initial
Ca2+ level was fully restored. Similarly, leupeptin protected the vesicles from
the reaccumulation deficit induced by Ca2+. The authors' findings suggest that
proteolysis activated by a Ca2+-sensitive protease may account for the direct in
vitro demonstration of CICR; such an effect may more likely reflect a role in
apoptosis than excitation-contraction coupling.
PMID- 9633822
TI - Fibroblast growth factor-2 and TPA enhance prostate-cancer-cell proliferation and
activate members of the Ras and PKC signal transduction pathways.
AB - Rat prostate-cancer-cell stable-transfectants expressing either antisense
fibroblast growth factor (FGF-1) or antisense-FGF-2 transcripts that respectively
have either undetectable FGF-1 or profoundly diminished FGF-2 protein content,
were used for analyses of FGF-2 and/or 12-O-tetradecanoylphorbol 12-acetate (TPA)
modulation of cell proliferation. Antisense-FGF-2 transfectant doubling-time was
2.6-fold greater than that of vector-control transfectants. FGF-2 and TPA
respectively caused 2.5- and 3.0-fold reductions in antisense-FGF-2 transfectant
doubling-time. Culture of antisense-FGF-2 transfectants in medium containing both
FGF-2 and TPA further reduced their doubling time; however, this effect was not
statistically different from that achieved by TPA treatment alone. Antisense-FGF
1 transfectant doubling-time was 2.2-fold greater than that of vector-control
transfectants and was reduced 2.0- or 2.3-fold, respectively, when these cells
were cultured in medium containing FGF-2 or TPA. In contrast to the results for
antisense-FGF-2 transfectants, culture of antisense-FGF-1 transfectants in medium
containing both FGF-2 and TPA caused a 2.6-fold reduction in transfectant
doubling-time that was significantly greater than that caused by independent
treatment with either FGF-2 or TPA. FGF-2 promoted rapid activation of rat
prostate-cancer-cell PKCalpha and PKCepsilon, as assessed by isozyme
translocation from the soluble to particulate cell fraction, and only moderately
altered PKCdelta distribution. By contrast, TPA promoted rapid activation of all
three PKC isozymes. Both the TPA- and FGF-2-mediated PKC activation were
prolonged and possibly involved cyclic redistribution of isozymes between soluble
and particulate cell fractions. FGF-2 also caused rapid phosphorylation of
prostate-cancer-cell Shc, the adapter protein that mediates FGF-receptor
modulated ras signaling. The results of these studies indicate that FGF-2 and TPA
independently and conjointly modulate rat prostate-cancer-cell antisense
transfectant doubling time and suggest that effector modulation of rat prostate
cancer-cell proliferation is achieved by processes involving PKC and/or ras
mediated signaling.
PMID- 9633824
TI - IGF-I receptor protection from apoptosis in cells lacking the IRS proteins.
AB - The type I insulin-like growth factor receptor (IGF-IR) plays a crucial role in
cell growth, transformation and protection from apoptosis. Although the mitogenic
function of the IGF-IR may require the activation of insulin receptor substrate-1
(IRS-1) or IRS-2, an overexpressed IGF-IR is able to protect 32D cells, which
lack IRS-1 and IRS-2, from apoptosis caused by Interleukin-3 (IL-3) withdrawal.
Here, using mutational analysis, the authors identify domains of the IGF-IR
necessary to protect from apoptosis without downstream signaling from IRS-1 and
IRS-2. A receptor mutant of the tyrosine kinase (TK) domain only partially
inhibited antiapoptotic signaling, whereas a mutant displaying constitutive
autophosphorylation of the receptor did not show enhanced survival activity.
Surprisingly, survival signaling was dependent upon tyrosine 950, the binding
site for IRS-1, IRS-2, and Shc proteins. Yet, overexpressed Shc and/or IRS-1
could not replace the IGF-IR survival signal, suggesting the existence of other
critical substrates. Finally, the C-terminus may encode a proapoptotic signal, as
receptors truncated at C-terminal residues 1229 or 1245 were found to inhibit
apoptosis better than the wild type (WT) IGF-IR.
PMID- 9633825
TI - Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung
fibroblast cell line WI-38.
AB - Protein tyrosine phosphatases are important components of signal transduction
pathways. The authors have used reverse transcription/polymerase chain reactions
to accomplish a comprehensive examination of the RNA expression for 58 distinct
mammalian protein tyrosine and dual specificity phosphatase (PTPase) and PTPase
like genes in the normal human diploid fibroblast cell line WI-38. Thirty-seven
of these PTPase genes express easily measurable RNA, and four simultaneously
express the RNA for two or more isoforms. Messages for an additional eight PTPase
genes are detectable at low levels. Only 14 known PTPase genes do not express
measurable RNA under our conditions. For purposes of comparison, the authors also
assessed the PTPases expressed in the WI-38 cell line using highly degenerate
primers to conserved motifs found in the classical tyrosine-specific PTPases.
Only eight of the 22 classic tyrosine-specific PTPases detected using the
specific primers were detected using these degenerate primers. Our panel of
specific PTPase primers should be very useful for semiquantitatively assessing
the repertoire of PTPases expressed by cells.
PMID- 9633826
TI - Limited proteolysis for assaying ligand binding affinities of nuclear receptors.
AB - The binding of natural or synthetic ligands to nuclear receptors is the
triggering event leading to gene transcription activation or repression. Ligand
binding to the ligand binding domain of these receptors induces conformational
changes that are evidenced by an increased resistance of this domain to
proteases. In vitro labeled receptors were incubated with various synthetic or
natural agonists or antagonists and submitted to trypsin digestion. Proteolysis
products were separated by SDS-PAGE and quantified. The amount of trypsin
resistant fragments was proportional to receptor occupancy by the ligand, and
allowed the determination of dissociation constants (kDa). Using the wild-type or
mutated human retinoic acid receptor alpha as a model, kDa values determined by
classical competition binding assays using tritiated ligands are in agreement
with those measured by the proteolytic assay. This method was successfully
extended to human retinoic X receptor alpha, glucocorticoid receptor, and
progesterone receptor, thus providing a basis for a new, faster assay to
determine simultaneously the affinity and conformation of receptors when bound to
a given ligand.
PMID- 9633827
TI - Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts
from pathological human parathyroid glands.
AB - Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic
properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and
ETB subtypes) display expression in numerous tissues and possibly mediate
autocrine/paracrine actions. The present investigation shows that ET-1 triggers
biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in
pathological human parathyroid cells. Both the peak and sustained [Ca2+]i
increase, as well as the proportion of responding cells, are dose-dependent in
the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1
induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating
functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers
parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+
concentrations, and parathyroid cell ET release is inhibited by increases of
external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during
monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive
[Ca2+]i spikes, but show no response to elevation of external Ca2+. These
findings imply that ET secretion and ET receptor expression may constitute an
autocrine/paracrine mechanism in the regulation of human PTH secretion.
PMID- 9633828
TI - Signaling pathways in the induction of c-fos and c-jun proto-oncogenes by 3
methylcholanthrene.
AB - 3-methylcholanthrene (MC), a potent promutagen and procarcinogen, is also an
inducer of mammalian CYPIAI (cytochrome P1-450) gene. The CYPIAI enzyme is
responsible for the detoxification of MC and its oxidation into reactive epoxide
intermediates. Through its epoxide metabolites, MC functions also as an inducer
of drug-metabolizing enzyme glutathione S-transferase (GST) gene expression.
Induction of murine GST Ya gene by MC and a variety of other chemical agents is
mediated by a regulatory element composed of two adjacent AP-1-like sites, and
activated by the Fos/Jun heterodimeric complex (AP-1). In cultured cells, MC
causes the induction of AP-1 activity, which is the result of an increased
expression of c-Fos and c-Jun proteins. The mechanisms involved in MC activation
of c-fos and c-jun gene expression were examined in the present study. Evidence
is presented that stimulation of c-fos transcription by MC involves a signal
transduction pathway, which includes activation of the small G protein Ras, Raf-1
kinase, and the mitogen-activated protein (MAP) kinases, ERK1 and ERK2.
Furthermore, we find that phorbol 12-myristate 13-acetate, which uses both
protein kinase C and protein-tyrosine kinase activities to induce c-fos promoter,
may share a common pathway with MC downstream of Ras. The signal transduction
pathway induced by MC to stimulate c-jun promoter involves Ras activation and the
JNK group of MAP-kinases.
PMID- 9633829
TI - Responsiveness of vaginal cells to estradiol during postnatal development of rat.
AB - Ontogeny of responsiveness to hormones is mainly regulated by the presence of
receptors; their type, number, and location in the hormone target cells. Some of
these parameters have been used to study the responsiveness of rat vagina to
estradiol. The estrogen binding sites (EBS) in the cytosol of rat vagina are
present immediately at birth, however the animal becomes responsive to the
hormone only after 25 +/- 5 d of age. The authors demonstrate how the serum and
tissue levels of estradiol affect the EBS in this tissue during the postnatal
development of the rat. The various responses observed after a single i.p.
injection of estradiol in the immature rats are explained based on the status of
the binding sites for estrogen in this tissue.
PMID- 9633830
TI - Demonstration of complimentarity between monoclonal antibodies (MAbs) to human
chorionic gonadotropin (hCG) and polyclonal antibodies to luteinizing hormone/hCG
receptor (LH-R) and their use in better understanding hormone-receptor
interaction.
AB - We have earlier reported that polyclonal antisera raised in rabbits to a
luteinizing hormone/chorionic gonadotropin receptor (LH-R) purified from sheep
luteal tissue has antibodies exhibiting hormone agonistic and antagonistic
activities. Western blot analysis showed this antibody (LHR-anti IgG) to be
highly specific to sheep luteal LH receptor (LH-R) (Jeyakumar and Moudgal, 1991).
Using this, along with a battery of mouse monoclonal antibodies (MAbs) to hCG, an
attempt has been made to better understand the interaction of LH/hCG with its
receptor. Of the eight hCG MAbs screened, three (B14/B7, B52/18 and A7/G4) were
specific to the beta-subunit; while a second set of three (G10/F7, H9/E9 and
B52/21) were specific to the alpha-subunit. Two additional MAbs (B52/28 and
F9/G8) did not recognize individual subunits, but bound like the rest intact hCG.
Both 125I hCG and 125I anti LHR-IgG bound specifically to ovine luteal membrane
LH-R. Assuming that a certain degree of similarity should exist between hCG and
LHR-anti IgG, different hCG MAbs were tested for their ability to block the
binding of either 125I hCG or 125I LHR-anti IgG to sheep luteal LH-R. It appears
that hCG and LH-R share a minimum of four sites that are complementary to each
other and these are recognized by the hCG MAbs B14/B7, G10/F7, A7/G4, and H9/E9.
Whereas two of the MAbs B14/B7 and G10/F7 blocked the binding of both 125I
labeled hCG and LHR-anti IgG to the receptor, MAbs A7/G4 and H9/E9 only inhibited
the binding of 125I LHR-anti IgG to the LH-R. Although individually B14/B7 and
G10/F7 blocked the binding of 125I LHR-anti IgG to LH-R to a maximum extent of
43%, together they inhibited binding by as much as 80%. The ability of B14/B7 to
inhibit binding of 125I LHR-anti IgG to the receptor was also significantly
increased by the addition of A7/G4. Finally, by demonstrating direct binding of
the immobilized hCG MAbs B14/B7, G10/F7, A7/G4, and H9/E9 to LHR-anti IgG, we
have been able to establish that the receptor binding sites of hCG and LHR-anti
IgG are complementary and that a set of four sites are recognizable by the hCG
MAbs. From the degree of interaction, it appears that two sites recognized by
MAbs B14/B7 and G10/F7 (representing a site each in the beta- and alpha-subunit
of hCG) have a prominent role in the interaction of hCG with its receptor. Thus,
this study has provided us with an opportunity to investigate the interaction of
LH/hCG with its receptor by an indirect approach of monitoring the binding of
their respective antibodies with each other.
PMID- 9633831
TI - The New York High-Risk Project: social and general intelligence in children at
risk for schizophrenia.
AB - Social deficits, as well as low performance on intelligence tests, are known
early symptoms of schizophrenia. We studied whether impairment of social
intelligence can be detected before the outbreak of the disorder. In the New York
High-Risk Project, children at risk for schizophrenia (HRSz) or affective
disorder (HRAff) and a normal control group (NC) were studied over the past 26
years. The children are now in mid-adulthood, with known psychiatric outcomes.
Developmental and clinical data from childhood can now be related to adulthood
diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from
childhood and adolescence, and change of IQ, between the risk groups, as well as
between the adulthood outcomes. We were specifically interested in the
development of social intelligence (the Picture Arrangement and Comprehension
subtests). We used logistic regression analyses to generate a model predicting
adulthood schizophrenia. RESULTS: IQ at age 9,7 was lower in children with HRSz
than with HRAff. Adulthood schizophrenia, compared with major depressive disorder
and no psychiatric diagnosis could not be related conclusively to low IQ. This
may be a result of the study design, since children with IQ below 70 or
behavioral problems were not eligible as study subjects. There was no evidence of
lower scores or more decline in social intelligence related to age or group
membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the
differences between all subtests and Vocabulary, reflecting a lesser difference
between crystallized and fluid intelligence, was identified as a significant
predictor of adulthood schizophrenia, in the whole group as well as in the HRSz
group alone.
PMID- 9633832
TI - No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic
patients studied with PET.
AB - To investigate putative abnormalities of cortical 5-HT2A receptor density in
schizophrenia, we used positron emission tomography and [18F]setoperone, a high
affinity 5-HT2A receptor radioligand, in 14 neuroleptic-free or -naive
schizophrenic patients and in 15 normal controls. No significant difference
between the groups was observed in the whole or regional cortical binding
potential of [18F]setoperone, indicating an absence of major 5-HT2A receptor
cortical density abnormalities in schizophrenics.
PMID- 9633833
TI - Psychomotor slowing, negative symptoms and dopamine receptor availability--an
IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients.
AB - Anhedonia and psychomotor slowing in schizophrenia have been attributed to a
dysfunction of dopaminergic neurotransmission. To differentiate between disease
and drug-induced negative symptoms, we examined eight drug-free and eight
neuroleptic-treated schizophrenic patients. Positive and negative symptoms and
extrapyramidal side effects were assessed using standardized rating scales (PSAS,
AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer
aided system and striatal dopamine D2/D3 receptor availability was assessed using
[I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening
and avolition were increased in treated patients relative to the untreated cohort
and were negatively correlated with dopamine D2/D3 receptor availability.
Significant positive correlations were found between parkinsonism and affective
flattening and between psychomotor slowing and avolition. Positive symptoms were
not significantly associated with striatal IBZM binding. These findings support
the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum
can mimic certain negative symptoms, such as affective flattening and avolition,
and indicates that psychomotor testing may be helpful in differentiating between
disease and drug-induced negative symptoms.
PMID- 9633834
TI - Neuropeptide Y-mediated enhancement of NMDA-stimulated [3H]dopamine release from
rat prefrontal cortex is reversed by sigma1 receptor antagonists.
AB - Sigma (sigma) receptors are located in limbic areas, including the prefrontal
cortex, where decreased dopamine levels have been linked to negative symptoms.
Although the endogenous ligands for sigma receptors are unknown, neuropeptide Y
(NPY) has been named as the potential endogenous agonist at these receptors. NPY
enhanced NMDA-stimulated [3H]dopamine release in rat prefrontal cortex. This was
in contrast to the inhibition produced by the sigma agonists (+)pentazocine and
BD737. However, four sigma antagonists, including one which is sigma1 selective,
that reverse (+)pentazocine- or BD737-mediated inhibition all reversed the NPY
mediated enhancement. In addition, PYX-1, a Y receptor antagonist, reversed both
the (+)pentazocine- and BD737-mediated inhibition and the NPY-mediated
enhancement of release. Peptide YY (PYY), [Leu31,Pro34]NPY and NPY(13-36) did not
mimic the effect of NPY. Our findings are consistent with NPY acting as an
endogenous ligand for a subtype of sigma receptor with characteristics different
from Y1, Y2 and Y3 receptors but sensitive to PYX-1. These findings suggest a
role for NPY, via sigma receptors, as a modulator of dopamine levels in the
prefrontal cortex.
PMID- 9633835
TI - High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort
Test performance in controls, not in schizophrenics: a 31phosphorus magnetic
resonance spectroscopic and neuropsychological investigation.
AB - In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS)
studies on the frontal lobe of schizophrenics have been performed, reporting
alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b)
recently found positive correlations between left frontal phosphomonoester%
(PME%) levels and the performance of a specific frontal lobe task, the Wisconsin
Card Sorting Test (WCST), in schizophrenics. In the present paper, the
correlations between phospholipids and high-energy phosphates in the frontal lobe
of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS
method were investigated. Overall, we could not find any correlations between
WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and
PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test
performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is
consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr%
values and, moreover, increased PCr/ATP ratios point to a decreased ATP
consumption. Thus, the correlations found between PCr% and PCr/ATP and test
performance in controls point to an association between reduced performance in a
specific frontal lobe task and decreased energy demanding processes at rest. This
association was not found in schizophrenics, possibly due to the influence of
neuroleptic medication or the disease process per se.
PMID- 9633836
TI - Increased levels of CD8+ and CD4+ 45RA+ lymphocytes in schizophrenic patients.
AB - Peripheral blood (PB) lymphocyte subpopulations, IgG, IgM, IgA and IgE serum
immunoglobulins and C3 and C4 complement fractions were evaluated in 29
schizophrenic patients, 31 of their relatives and 20 healthy subjects. The
patients fulfilled DSM-III criteria for schizophrenia, and were unmedicated for 3
months prior to the PB sample collection. When compared to healthy controls and
their own relatives, the schizophrenic patients showed a lower level of CD4+
cells, while the CD4+ 45RA+ (naive) subset was significantly higher. Conversely,
the number of CD4+ 45RA- (memory) lymphocytes was significantly lower in
schizophrenic patients in comparison to their relatives and controls, while the
CD8+ supressor/cytotoxic T-cell percentage was significantly higher. No
significant differences were observed for the IgG, IgM, IgA, IgE and C3 and C4
complement fraction levels among the three groups. The present data confirm the
presence of immunological abnormalities in schizophrenic patients and suggest a
possible role of environmental factors in the triggering of an autoimmune
pathogenic mechanism.
PMID- 9633837
TI - The structure of schizophrenic symptoms: a meta-analytic confirmatory factor
analysis.
AB - To quantitatively review all presently available evidence about the
interrelations between positive and negative schizophrenic symptoms, we created
an aggregate matrix of the intercorrelations among schizophrenic symptoms by
combining data from 28 independent samples using meta-analytic procedures (net
bivariate dfs ranging from 683 to 1657). Using confirmatory factor analyses, we
then statistically compared four theoretically derived models of the structure of
schizophrenic symptoms. Although a three-factor model (Liddle, 1987) best fit the
data, results suggest that either more factors or different symptoms are required
to account well for the latent structure underlying schizophrenic symptomatology.
The nature of such augmented approaches, the opportunities and constraints
inherent to multifactorial models, and the limitations of current instruments are
discussed.
PMID- 9633838
TI - Clinical pathways and treatment algorithms in oncology patients: "not bad" but
are they beneficial?
PMID- 9633839
TI - Epidemiology and risk assessment for ovarian cancer.
AB - The incidence of ovarian cancer varies internationally with higher rates among
women of North America and northern Europe. In the United States, there has been
relatively little change in the incidence of ovarian cancer in recent decades.
The incidence rate of ovarian cancer is highest among white and Hawaiian women,
intermediate among African-American, Hispanic and Asian-American women, and
lowest among Native American women. The most intensively studied risk factors
have been family history, pregnancy history, and oral contraceptive use.
Multiparity, lactation, oral contraceptive use, and tubal ligation/hysterectomy
all decrease a woman's risk of ovarian cancer. One exposure that has been
consistently associated with increased ovarian cancer risk is cosmetic talc
applied to the perineum.
PMID- 9633840
TI - Genetics and ovarian carcinoma.
AB - Ovarian cancer is a disease that will affect approximately 1% of American women
during their lifetime, and contributes to more than 14,000 deaths annually. If
not detected early, this disease has a 5-year survival rate of less than 20%.
Ovarian cancer develops predominantly from the malignant transformation of a
single cell type, the surface epithelium. Although the biological mechanisms of
transformation remain unclear, it is probably a multistep process requiring an
accumulation of genetic lesions in a number of different gene classes. Several
proto-oncogenes, such as AKT2 and Ki-RAS, are activated during ovarian cancer
development, with putative oncogene-containing chromosomal regions showing
imbalances and DNA amplifications. A number of chromosomal regions are also lost
in ovarian tumors, indicating that the inactivation of tumor suppressor genes,
such as TP53, may also contribute to cancer development. An important recent
advancement in the field of ovarian cancer research is the identification of the
breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2. Mutations in these
two tumor suppressor genes are responsible for the majority of heritable forms of
epithelial ovarian cancers. A second class of genes involved in DNA mismatch
repair (MMR) are responsible for most cases of hereditary nonpolyposis colorectal
cancer (HNPCC). HNPCC or Lynch II cancer syndrome patients are also at an
increased risk for developing ovarian cancer. Individuals in cancer-prone
kindreds are currently being screened for germline mutations in BRCA1, BRCA2, and
several MMR genes (eg, MSH2, MLH1), and mutant allele carriers counseled for
cancer risks. Issues related to counseling and management of women at high risk
for developing ovarian cancer are discussed. Although BRCA1, BRCA2, and a number
of MMR genes have been identified, many more genes involved in gynecologic
malignancies remain to be discovered and the clinical significance of the cancer
genes already known is still in its infancy.
PMID- 9633841
TI - The biology of ovarian cancer.
AB - The biology of ovarian cancer broadly defined covers essentially all aspects of
the disease from how it arises to how it responds to chemotherapy, often becomes
refractory to treatment, and ultimately kills the patient. In this article, we
take the liberty of discussing many of these issues to some degree in context of
the "natural/clinical" history/biology of the disease. We focus on concepts of
how the disease develops, efforts to identify histologic changes that may precede
the development of overt ovarian cancer, efforts to define how the growth and
function of the normal ovarian surface epithelium are regulated to gain insights
into how aberrant function of these pathways may contribute to the initiation of
the disease, molecular biological studies on clinical ovarian cancer specimens,
efforts to experimentally induce the malignant transformation of ovarian surface
epithelial cells, and efforts to understand why ovarian cancer is often initially
responsive to chemotherapy but ultimately becomes refractory.
PMID- 9633842
TI - Prognostic factors in ovarian cancer.
AB - There is obvious merit in being able to accurately predict outcome and tailor
treatment according to individual risk and potential for benefit. Epithelial
ovarian cancers are characterized by a broad spectrum of biological behavior
ranging from tumors that have an excellent prognosis and high likelihood of cure
to those that progress rapidly and have a very poor prognosis. This wide clinical
spectrum is partly reflected by a number of clinicopathological prognostic
variables which include International Federation of Gynecology and Obstetrics
stage, histologic subtype and grade, volume of residual tumor remaining after
surgical resection, performance status, and age. There has been increasing
interest by many groups to incorporate the independent prognostic variables into
multivariate models that could better predict outcome. This approach does appear
to allow the identification of different prognostic subsets and requires
confirmation in prospective studies. There has been, and there continues to be a
lot of effort in identifying new prognostic factors that have a biologic
rationale and these will be discussed. Most of these new prognostic factors have
not been subjected to rigorous testing and this will be clearly necessary before
they find clinical application. This is an area that is rapidly evolving with the
increased understanding of the molecular basis for ovarian carcinogenesis and
progression coupled with technological advances such as DNA arrays and automated
polymerase chain reaction. We are at the threshold of developing a new and more
objective as well as rational approach to predict prognosis and response to
therapy.
PMID- 9633843
TI - Ovarian cancer screening.
AB - Despite advances in molecular biology, surgical oncology, and chemotherapy, the
prognosis for ovarian cancer remains poor. The excellent survival rates for stage
I disease provide the rationale for efforts to screen for early-stage ovarian
cancer. However, there are doubts about the feasibility of screening related to
the natural history of the disease, the performance of the available tests, and
health economic considerations. The investigators use the World Health
Organization criteria for a screening program as a framework for discussing
current issues in ovarian cancer screening. These include screening modalities
and strategies, high- and low-risk populations, and the acceptability,
psychological impact, and cost of screening. As a result of developments during
the last decade, there are now real prospects for practical and effective ovarian
cancer screening programs. Research to date has made important progress, but
information about the impact of screening on mortality from ovarian cancer is
still awaited. Three large randomized controlled trials of ovarian cancer
screening are currently recruiting volunteers and will yield important results in
the next few years.
PMID- 9633844
TI - The role of surgery in the management of ovarian cancer: primary and interval
cytoreductive surgery.
AB - Ovarian cancer remains the number one cause of mortality in gynecologic
malignancies and the fifth most common cause of death among all malignancies in
women. Unfortunately, recent data confirm that only approximately 90% of
"apparent" early ovarian cancer are inadequately staged, and only approximately
80% of patients with advanced-stage disease are adequately staged. Interval
debulking surgery, a newer treatment modality, appears to have a promising role
for patients who cannot be adequately debulked at their initial surgery. Second
look laparotomy continues to be the most accurate way to document responses to
chemotherapy in protocol settings, but additional clinical trials with newer
second-line chemotherapy will be necessary before definitive statements can be
made with regard to survival advantages in patients who undergo second-look
laparotomy.
PMID- 9633845
TI - Management of early ovarian cancer.
AB - About one third of the women diagnosed with ovarian cancer present with localized
disease. Accurate surgical staging is required to properly evaluate these
patients, define appropriate treatment, and establish prognosis. A series of
recent studies have clarified which patients can be managed with comprehensive
surgical staging and disease removal alone, and which may benefit from adjuvant
therapy. A series of national and international prospective randomized trials are
evaluating a variety of adjuvant treatments that may enhance long-term survival
in those patients with early ovarian cancer who do require additional therapy.
PMID- 9633846
TI - Chemotherapy of advanced ovarian cancer.
AB - Combination chemotherapy with paclitaxel plus a platinum compound (carboplatin or
cisplatin) is the current regimen of choice for the treatment of advanced
epithelial ovarian cancer. The two most widely used combinations are paclitaxel
(135 mg/m2, 24-hour infusion) plus cisplatin (75 mg/m2) or paclitaxel (175 mg/m2,
3-hour infusion) plus carboplating dosed to an area under curve of 7.5.
Randomized trials are in progress comparing these two regimens. Numerous other
clinical issues remain regarding how to maximize the effectiveness of this
therapy, including dose and schedule, duration of treatment, route of
administration, and incorporation of other agents with novel mechanisms of
cytotoxicity. New agents currently undergoing evolution as part of novel
induction regimens have been shown to have significant activity in recurrent
ovarian cancer and include topotecan, gemcitabine, oral etoposide, and
encapsulated doxorubicin.
PMID- 9633847
TI - Multiple cycles of high-dose chemotherapy for ovarian cancer.
AB - Recent advances in hematopoietic support have extended the application of high
dose chemotherapy in the treatment of malignancy. The use of colony-stimulating
factors and peripheral blood progenitor cells significantly have decreased the
morbidity and mortality of such treatment compared with traditional autologous
bone marrow transplantation. These innovations facilitate the use of multiple
cycles of high-dose chemotherapy as consolidation after achieving best response
to conventional chemotherapy or as initial treatment. Developing data suggest
that this approach in both of these settings merit further evaluation for the
treatment of epithelial ovarian carcinoma.
PMID- 9633848
TI - Intraperitoneal therapy of ovarian cancer.
AB - During the past decade, intraperitoneal chemotherapy has evolved from a
theoretical concept into a rational therapeutic strategy for a select group of
individuals with ovarian cancer. Patients who may potentially benefit from this
approach include those with small volume intraperitoneal disease at the
initiation of initial chemotherapy and individuals with microscopic and very
small volume macroscopic cancer after the completion of front-line systemic
treatment. Further exploration to define an ultimate role for regional
antineoplastic drug delivery in the management of ovarian cancer is warranted.
PMID- 9633849
TI - Update on the role of radiotherapy in ovarian cancer.
PMID- 9633850
TI - Management of borderline tumors of the ovary: state of the art.
AB - Evidence published during several decades has shown that there is a group of
epithelial ovarian tumors having histological and biological features between
those of clearly benign and frankly malignant tumors. In 1963, FIGO accepted an
intermediate group of ovarian carcinomas of low malignant potential. In 1973, WHO
adopted the term borderline malignancies to describe these tumors. Borderline
tumors represent approximately 10% to 15% of all epithelial ovarian malignancies.
There are considerable discrepancies in the reported incidence of ovarian tumors
of borderline malignancies. Some centers do not recognize tumors of this type and
include them among invasive cancers. The prognosis for patients with borderline
tumors is generally considered to be excellent. Although the standard treatment
for older patients is abdominal hysterectomy and bilateral salpingo-oophorectomy,
many young patients who have not completed childbearing can be safely treated
with unilateral salpingo-oophorectomy coupled with comprehensive surgical
staging, thereby preserving fertility potential. Even ovarian cystectomy has been
reported, but the recurrence rate in the ovary approximates 15%. Many experts
strongly believe that surgery is the only effective treatment for borderline
tumors. Others routinely use postoperative chemotherapy for at least some subsets
of patients with peritoneal implants. Currently, insufficient information is
available to make a definitive statement regarding the efficacy of postoperative
therapy. Nevertheless, clinicians are faced with the difficult task of making
treatment recommendations to anxious patients. In the past, extensive application
of automated methods for analytical cytology has resulted in large quantities of
data on ploidy abnormalities in different types of human cancers. The main
purpose has been to obtain additional parameters for the characterization of
various types of malignancy to give more precise information on their biological
behavior. Data from the Norwegian Radium Hospital showed that the majority of
borderline tumors have DNA diploid tumors and good prognosis, DNA aneuploidy
indicates high risk. Several other investigators have shown the same results on
DNA ploidy as a predictor of recurrence and survival, but a few others have shown
conflicting results. Early studies suggest that p53 mutation does not appear to
play a role in the pathogenesis of these tumors. Studies on other molecular
markers have not yet uncovered a reliable predictor of biologic behavior.
However, it is hoped that future studies of genetics and molecular biology of
these tumors will lead to useful laboratory tests.
PMID- 9633851
TI - Biological therapy of ovarian cancer: current directions.
AB - Despite recent advances in the chemotherapy of ovarian cancer, the development of
alternative therapies that retain activity against drug-resistant tumors remains
a high priority. Our knowledge regarding growth factors, cytokines, and the
immune response continues to expand, and molecular biology has provided an
increased diversity of reagents for clinical evaluation. This review focuses on
regulatory targets in ovarian cancer, including Her2/neu (c-erbB2) and other
growth factor receptors; interferons, interleukins, and other immunoregulatory
cytokines; cellular adhesion molecules; antigen-specific T lymphocytes and
adoptive immunotherapy; choice of monoclonal antibody reagents and advances in
antibody engineering, including recombinant single-chain binding sites, chimeric
proteins, radioconjugates, cytotoxic drug conjugates, immunotoxins, and
bispecific antibodies. Although specific roles for biologic therapy in the
management of ovarian cancer have yet to be defined, current priorities for
clinical research are reviewed.
PMID- 9633852
TI - Gene therapy for ovarian carcinoma.
AB - Originally conceived and applied for the treatment of inherited monogenetic
defects such as adenosine deaminase deficiency and cystic fibrosis, gene therapy
was later applied to the treatment of cancer. Such a genetic strategy seemed
rational given the recognition that cancer typically develops in a multistep
process involving alterations of a number of different genes as demonstrated in
familial polyposis and colorectal cancer through the work of Vogelstein et al.
Because of the numerous alterations that may result in the eventual development
of cancer, there is no obvious single choice for a therapeutic gene. Although one
may view this as an obstacle, it also allows for a variety of possible
therapeutic interventions. This review focuses on the known genetic defects that
occur in ovarian cancer, the gene therapy strategies suggested by such defects,
and the approaches under current development for the treatment of this disease.
As such, this work also describes some of the approved human gene therapy
protocols. Finally, an overview of the problems and directions for future growth
and research is presented.
PMID- 9633853
TI - Ovarian germ cell tumors: an update.
AB - Ovarian germ cell tumors, while very rare, are important beyond their incidence
because they occur in young people and they are highly responsive to appropriate
treatment. Since 1991, when this topic was last discussed in Seminars in
Oncology, there have been a few important publications specifically devoted to
ovarian germ cell tumors. In addition, a number of important studies have added
to the knowledge base of chemotherapy in testis cancer. This article reviews and
updates progress made in this field.
PMID- 9633854
TI - Multi-ethnicity.
PMID- 9633855
TI - Smoking estimate correction.
PMID- 9633856
TI - WHO announces flu vaccine formula for 1998-1999.
PMID- 9633857
TI - Surveillance for avian influenza continues.
PMID- 9633858
TI - Vaccines under development could save up to eight million lives yearly.
PMID- 9633860
TI - U.S. and Russia cooperate in infectious disease research.
PMID- 9633859
TI - Comprehensive survey of working women's health issued.
PMID- 9633861
TI - Ways to stop family violence need to be evaluated.
PMID- 9633862
TI - Children's health insurance.
PMID- 9633863
TI - Public Health Service: on the job for 200 years.
PMID- 9633864
TI - Health cost containment: what it will mean for workers and local economies.
AB - After decades of rapid growth, the rate of increase in health services spending
appears to be moderating. Although a slowdown in health expenditure growth would
release resources for other uses in the economy, concerns have been raised about
the effects of a spending slowdown on health workers and regional economies.
Based on projections carried out by the Bureau of Labor Statistics during the
health reform debate and on state health sector employment data, the author
concludes that health workers may experience costly dislocation as health
spending growth slows, and some regions may be more affected than others.
However, the appropriate response is a general economic policy supporting
economic growth and full employment policy with regard to health expenditure
growth cannot be held hostage to concerns about employment effects.
PMID- 9633866
TI - Poisoning mortality, 1985-1995.
AB - Poisoning was reported as the underlying cause of death for 18,549 people in the
United States in 1995 and was ranked as the third leading cause of injury
mortality, following deaths from motor vehicle traffic injuries and firearm
injuries. Poisoning was the leading cause of injury death for people ages 35 to
44 years. Poisoning death rates were higher in 1995 than in any previous year
since at least 1979. From 1990 to 1995, the age-adjusted rate of death from
poisoning increased 25%; all of the increase was associated with drugs. About
three-fourths of poisoning deaths (77%) in 1995 were caused by drugs. The age
adjusted rate of drug-related poisoning deaths for males (7.2 per 100,000) in
1995 was more than twice that for females (3.0 per 100,000). From 1985 to 1995,
poisoning death rates for males ages 35-54 years nearly doubled to 20.4 per
100,000, and the drug-related poisoning death rate for males ages 35-54 years
nearly tripled, reaching 16.1 per 100,000. From 1990 to 1995, death rates
associated with opiates and cocaine more than doubled among males ages 35-54
years. The numbers of opiate and cocaine poisoning deaths for 1995 more than
doubled when all multiple cause of death codes were examined instead of only the
underlying cause of death codes.
PMID- 9633868
TI - Should the vaccine injury compensation program be expanded to cover adults?
AB - In 1996, the National Vaccine Advisory Committee (NVAC) asked for a review of the
pros and cons of including adult influenza and pneumococcal vaccines in the
Vaccine Injury Compensation Program (VICP). The authors, as staff to the
subcommittees charged with undertaking this assessment, looked at the following
questions: (a) Would inclusion in VICP of these two vaccines, used primarily for
adults, increase adult vaccination levels? (b) Is this Federal involvement
warranted based on the liability burden for these vaccines? (c) Does the risk of
adverse events following vaccinations warrant inclusion of these vaccines? (d) Is
there a consensus among stakeholders favoring their inclusion? To address these
questions, the authors reviewed information on adult vaccines, including data on
l lawsuits filed and reports of injuries, and sought input from interested
groups. They found no evidence that the use of influenza and pneumococcal
vaccines would increase if they were included in VICP. They found a low liability
burden for these vaccines, that serious adverse events were rare, and that no
consensus existed among stakeholders. After considering the staff report, NVAC
chose, in 1996, not to advise the Department of Health and Human Services to
include adult vaccines in VICP.
PMID- 9633870
TI - Defining the rabies problem.
PMID- 9633871
TI - The cost of rabies postexposure prophylaxis: one state's experience.
AB - OBJECTIVE: This study was undertaken to evaluate trends in the use of rabies
postexposure prophylaxis (PEP) before, during, and following an epidemic of
raccoon rabies in Massachusetts. METHODS: The authors reviewed initiation of PEP
as reported to the Massachusetts Department of Public Health (MDPH) from August
1994 to December 1995 and surveyed hospital pharmacies to determine the number of
vials of Human Rabies Immune Globulin (HRIG) dispensed from 1991 through 1995 and
charges to patients per vial. RESULTS: PEP use increased dramatically, from 1.7
per 100,000 population in 1991 (pre-epidemic) to 45 per 100,000 in 1995 (after
the first stages of the epidemic). The median costs per patient for biologics was
$1646 (range: $632-$3435). Including physician and emergency room charges, per
patient median costs were $2376 (range: $1038-$4447). Total health care charges
for PEP in Massachusetts in 1995 were estimated at $2.4 million to $6.4 million.
CONCLUSIONS: Given the rapid increase in use of PEP, further studies should be
undertaken to determine the appropriateness of use, and other alternatives, such
as oral wildlife vaccines, should be considered.
PMID- 9633872
TI - Dog and cat bites: epidemiologic analyses suggest different prevention
strategies.
AB - OBJECTIVE: To examine the characteristics of reported dog and cat bite incidents
in El Paso, Texas, and their implications for local bite prevention programs.
METHODS: The authors reviewed a random sample of reported dog bites and all
reported cat bites in El Paso, Texas, in 1995 using existing animal control
surveillance data. RESULTS: The majority of cat bites (89.4%) were provoked, with
females (57.5%) and adults (68.3%) more likely to be victims than males or
children. In contrast, just under half of dog bites (44.6%) were provoked, with
males (65.6%) and children (63%) more likely to be victims than females or
adults. Dogs that had not been vaccinated for rabies were involved in 65% of dog
bites and cats that had not been vaccinated for rabies were involved in 92% of
cat bites. CONCLUSION: Effective bite prevention programs should address the
finding that both restrained and unrestrained dogs may bite even when unprovoked
and that unrestrained cats usually bite when provoked.
PMID- 9633873
TI - Potential rabies exposures in a Virginia county.
AB - OBJECTIVE: Although records of animal bites and scratches are kept at most local
health departments, little is known about the epidemiology and characteristics of
these potential rabies exposures on a local level. Bite and scratch records for a
four-and-a-half-year period from Montgomery County, Virginia, were examined in
order to identify preventable trends. METHODS: The author retrospectively
reviewed animal bite and scratch records from the Montgomery County Health
Department dating from January 1992 through July 1996. RESULTS: Cat bites or
scratches involved stray or feral animals more than eight times as often as dog
bites or scratches. Cats were involved in the majority of incidents in which
rabies postexposure prophylaxis (PEP) was recommended. Overall, PEP was
recommended following 5.9% of reported incidents. The records also indicated that
65% of owned cats were unvaccinated at the time of the incident, while only 28%
of owned dogs were unvaccinated. Children under the age of 18 were significantly
more likely to be involved in a potential exposure than adults. CONCLUSIONS:
Potential exposures should be analyzed periodically by local health departments.
Suggestions for minimizing the number of potential rabies exposures in Montgomery
County based on the results of the study reported here include: reducing the
stray and feral cat population, targeting educational programs to children, and
encouraging owners to vaccinate their pets.
PMID- 9633874
TI - The effect of using "race of child" instead of "race of mother" on the black
white gap in infant mortality due to birth defects.
AB - OBJECTIVE: For at least 20 years, birth defects have been the leading cause of
infant mortality in the United States. Some studies have reported higher rates
for black infants than white infants of mortality due to birth defects, while
other studies have reported no black-white differences. The authors analyzed the
effect on these rates of a change in the way the National Center for Health
Statistics (NCHS) tabulates "race" for newborns. METHODS: The authors calculated
infant mortality rates due to birth defects for 1980-1993 using two standard
methods of assigning newborns to "racial" categories: a "race of child" algorithm
and the "race of mother" approach currently used by NCHS. RESULTS: From 1980
through 1993, birth defect-specific infant mortality rates (BD-IMRs) were
significantly higher for black infants than white infants 12 of the 14 years by
"race of mother" and only 5 of 14 years by "race of child." Calculation of BD
IMRs by "race of mother" reduced the rate for white infants and increased the
rate for black infants in each of the 14 years. The choice of method for
assigning newborns to "racial" categories had a progressively greater effect over
time on the black-white gap in BD-IMRs. CONCLUSIONS: Calculations of trends in
"race"-specific BD-IMRs by may vary substantially by whether "race of mother" or
"race of child" is used. Identifying the method of tabulation is imperative for
appropriate comparisons and interpretations.
PMID- 9633875
TI - The use of infrared ear thermometers in pediatric and family practice offices.
AB - OBJECTIVE: To describe the use of infrared (IR) ear thermometers in pediatric and
family practice offices. METHODS: The authors mailed a questionnaire to 350
randomly selected members of the American Academy of Pediatrics and to 355
randomly selected members of the American Academy of Family Physicians. RESULTS:
Of respondents in clinical practice, 78% had used IR ear thermometers at least
once in the past; 65% of pediatricians and 64% of family practice physicians were
current users. Seventeen percent of pediatric offices and 18% of family practice
offices that had used IR ear thermometers had discontinued use, most citing
inaccuracy or lack of staff trust in the device. Pediatric offices were less
likely than family practice offices to use the device in well neonates and sick
neonates and more likely to use it in sick children. Advantages cited included
rapid readings, ease of use, and accuracy. Seventy-five percent of current users
reported at least one problem, including low readings and lack of staff trust.
CONCLUSIONS: IR ear thermometers are widely used in pediatric and family practice
offices. Some offices limit use of these devices to older children and adults,
and most of the offices surveyed report using other devices as a check on the
accuracy of IR thermometers. Statements by professional organizations that
provide user guidelines and establish appropriate age cut-offs would be helpful.
PMID- 9633876
TI - Prevalence and correlates of dementia: survey of the last days of life.
AB - OBJECTIVES: To estimate the prevalence and correlates of dementia at death and to
assess the usefulness of death certificate data in the reporting of dementia.
METHODS: The authors analyzed next-of-kin interviews for 599 male and 628 female
decedents using data from the National Institute on Aging's Survey of the Last
Days of Life. RESULTS: Death certificate data in this population show the
prevalence of dementia to be less than 1%, consistent with previous reports based
on death certificates but a substantial underestimate compared to the 11.9%
reported in a national survey. Using a dementia index based on the informant's
report of whether the decedent had been diagnosed with a dementing illness and
the extent of her or his cognitive and functional limitations, this study found a
prevalence of dementia of 8.5%. A high score on the dementia index was
significantly associated with older age, Parkinson's disease, and incontinence.
Lower relative odds for dementia at death were found for people with either a
lifetime history or a death certificate report of cancer. Similarly, people with
a lifetime history of coronary heart disease were found to have lower relative
odds for dementia at death. CONCLUSION: These results suggest that informant
interviews may be a useful source of data to examine factors associated with
dementia and to estimate the prevalence of dementia in the last year of life.
PMID- 9633877
TI - Iron chelators for thalassaemia.
PMID- 9633878
TI - Red cell morphology and malaria anaemia in children with Southeast-Asian
ovalocytosis band 3 in Papua New Guinea.
AB - Southeast-Asian ovalocytosis (SAO) was diagnosed in children from Madang, Papua
New Guinea, by detection of the SAO band 3 gene variant using the polymerase
chain reaction. SAO band 3 was present in 16/241 (6.6%) children living in the
community and 32/389 (8.2%) children with acute Plasmodium falciparum malaria
(P=0.42). SAO band 3 was detected in 8.2% (23/281) of alpha+-thalassaemia
homozygotes, 9.4% (20/214) of heterozygotes and 2.4% (2/85) of children with a
normal alpha-globin genotype (P=0.12). The most consistent feature of SAO band 3
on microscopy of thin blood films was red cells with two or more linear or
irregularly-shaped pale regions. In children living in the community, these were
present in 15 with SAO band 3 (sensitivity 93.8%) and only two normals
(specificity 99.1%). The presence of > or = 20% ovalocytosis was a poorer
indicator of SAO band 3 (sensitivity 68.8% and specificity 100%). Haematological
data were similar in SAO band 3 and normal children. However, in children with
acute malaria, haemoglobin levels and red cell counts were significantly lower in
SAO band 3 than normal children. The degree of ovalocytosis was lower in children
with SAO band 3 during acute malaria, suggesting that a selective loss of
ovalocytes may contribute to malaria anaemia in Southeast-Asian ovalocytosis.
PMID- 9633879
TI - Liver iron and fibrosis during long-term treatment with deferiprone in Swiss
thalassaemic patients.
AB - Serum ferritin levels, hepatic histology and iron concentration were studied in a
'veteran' group of seven Swiss beta-thalassaemic patients after 93-99 months of
treatment with the oral iron chelator deferiprone (L1), and another four patients
who had received 54-82 months of L1 therapy. Despite continuous compliance,
unexplained resurgence of serum ferritin levels occurred in 4/7 patients of the
'veteran' group after 4-5 years on L1. In three of these a concomitant increase
of liver iron was also observed. Hepatic histology revealed significantly higher
degrees of fibrosis in 6/11 hepatitis C (HC)-positive patients (fibrosis scores 1
5, mean 3.0) than in the HC-negative group (fibrosis score 0-2, mean 0.8). Two HC
negative patients had no detectable fibrosis after 98 and 93 months on
deferiprone. Therefore the hepatic pathology in these patients cannot definitely
be attributed as a side-effect of deferiprone. Chronic active hepatitis C and the
accumulation of iron are the major causative factors to be considered.
PMID- 9633880
TI - Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin
concentration during hydroxyurea therapy in beta thalassaemia.
AB - Hydroxyurea increases fetal haemoglobin in many patients with sickle cell
anaemia, but its effectiveness in thalassaemia appears to be less consistent. We
describe the response to hydroxyurea in an adult male with homozygous beta
thalassaemia, symptomatic paraspinal extramedullary haemopoiesis, bone pain, and
progressive tissue iron loading. Prior to therapy with hydroxyurea the
circulating haemoglobin (Hb) concentration was 7.0 g/dl and absolute fetal
haemoglobin concentration was 5.0 g/dl. Administration of sodium phenylbutyrate
had induced no increase in either parameter. Subsequent therapy with hydroxyurea
was associated with increases in total haemoglobin to 9.0 g/dl, and in fetal
haemoglobin to 7.6 g/dl. Ineffective erythropoiesis was reduced and
extramedullary haemopoiesis regressed during therapy.
PMID- 9633881
TI - Plasma thrombopoietin levels in thrombocytopenic states: implication for a
regulatory role of bone marrow megakaryocytes.
AB - To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand)
measurements, and clarify the regulatory mechanisms of TPO in normal and in
thrombocytopenic conditions, the plasma TPO concentration was determined in
normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic
thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3),
chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome
(MDS; n = 11), and sequentially during peripheral blood progenitor cell
transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples
were used for the analysis. The plasma TPO concentration in the normals and
umbilical cord blood were 52 +/- 12 pg/ml and 66 +/- 12 pg/ml, respectively. The
corresponding values in patients with SAA and chemotherapy-induced bone marrow
hypoplasia were 1514 +/- 336 pg/ml and 1950 +/- 1684 pg/ml, respectively, and the
TPO concentration, measured sequentially after myeloablative chemotherapy and
peripheral blood progenitor cell transplantation, was inversely related to the
platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 +/-
20 pg/ml) and MDS (68 +/- 23 pg/ml) were only slightly higher than normal levels.
In conclusion, TPO levels were significantly elevated in patients in which bone
marrow megakaryocytes and platelets in circulation were markedly reduced, whereas
TPO levels were normal in ITP patients, and only slightly increased in the MDS
patients. These latter patients displayed a preserved number of megakaryocytes in
bone marrow biopsies. Our data support the suggestion that megakaryocyte mass
affects the plasma TPO concentration. In thrombocytopenic patients a
substantially increased plasma TPO implies deficient megakaryocyte numbers.
However, TPO measurements do not distinguish between ITP and thrombocytopenia due
to dysmegakaryopoiesis, as seen in MDS patients.
PMID- 9633882
TI - Effects of thrombopoietin on the proliferation and differentiation of primitive
and mature haemopoietic progenitor cells in cord blood.
AB - Thrombopoietin (TPO) is considered to be the primary growth factor for regulating
megakaryopoiesis and thrombopoiesis. In this study we investigated the in vitro
effect of TPO on relatively immature and mature CD34+ progenitor cells in cord
blood. Cells were cultured in both liquid and semi-solid cultures containing 50
ng/ml TPO. The CD34+/CD45RA- and CD34+/CD38- subfractions in cord blood were both
enriched for megakaryocyte progenitors as determined in a semisolid CFU-meg
assay. Progenitor cells derived from the CD34+/CD45RA- and CD34+/CD38-
subfractions showed high proliferative capacity in liquid cultures. We observed a
mean 19-fold expansion of the total CD34+ cell fraction, whereas in the
CD34+/CD45RA- and CD34+/CD38- subfractions the mean expansion was 23- and 50-fold
respectively. The expansion of the immature progenitor cell subfractions resulted
in a highly purified megakaryocyte suspension containing > 80% megakaryocytes
after 14 d in culture. However, these expanded megakaryocytes remained in a
diploid (2N) and tetraploid (4N) state. Maturation could not be further induced
by low concentration of TPO (0.1 ng/ml). The majority of the cells were 2N (80%)
and 4N (15%) and only 5% of the cells had a ploidy of more than 4N. These results
indicate that megakaryocyte progenitor cells in cord blood residing in the
immature stem cell fraction exhibit a high proliferative capacity when cultured
in the presence of TPO as the single growth factor, without maturation to
hyperploid megakaryocytes.
PMID- 9633883
TI - Evidence for differences in the mechanisms by which antibodies against CD44
promote adhesion of erythroid and granulopoietic progenitors to marrow stromal
cells.
AB - Adhesive interactions between haemopoietic progenitor cells and stromal elements
involve a number of different molecules, some of which may be progenitor- lineage
and stage-specific. CD44 is one such molecule, although little is known about
the mechanism(s) by which it is involved. In this study, several anti-CD44
monoclonal antibodies (mAb) increased the adherence of clonogenic cells, without
affecting the total number of types of progenitors recoverable from the adhesion
cultures. All of these mAb recognized epitopes on the globular head of CD44. In
contrast, two mAb that recognized other regions of CD44 reduced progenitor
adhesion to stroma. The mechanism by which one of the anti-CD44 mAb (L178)
enhanced progenitor adhesion did not involve CD44-crosslinking, and was
independent of VLA-4-, VLA-5- or LFA-1-mediated interactions, Ca or Mg cations,
or accessory cells. In addition, CD44 expression on both progenitors and stromal
cells contributed to L178-enhanced progenitor adhesion. Baseline adherence of
erythroid progenitors to stroma required tyrosine kinase activity, whereas that
of granulopoietic progenitors did not. However, the increase in adhesion did
require tyrosine kinase activation. Additional experiments suggested that
enhanced adhesion of CFU-GM to stroma may also be adenylate cyclase-dependent.
Taken together, the present studies indicate both similarities and differences in
the mechanisms of CD44-mediated adhesion of erythroid and granulopoietic
progenitors to stromal cells.
PMID- 9633884
TI - Interferon alpha activates the tyrosine kinase Lyn in haemopoietic cells.
AB - We investigated whether the src-family tyrosine kinase Lyn is involved in the
generation of interferon alpha (IFN alpha) signals in haemopoietic cells. In
vitro kinase assays using IFN alpha-sensitive cells of B-cell origin demonstrated
the presence of IFN alpha-dependent kinase activity in anti-Lyn
immunoprecipitates. Further studies demonstrated that Lyn associates via its src
homology 2 (SH2) domain with the Janus family tyrosine kinase Tyk-2. This
interaction was IFN alpha-dependent and involved direct binding of the SH2 domain
of Lyn to the IFN alpha-activated form of Tyk-2. Thus, during binding of IFN
alpha to its receptor in malignant haemopoietic cells, Lyn is engaged in an IFN
alpha-signalling pathway, probably downstream of Tyk-2.
PMID- 9633885
TI - A warfarin induction regimen for out-patient anticoagulation in patients with
atrial fibrillation.
AB - Currently available protocols for induction of warfarin anticoagulation employ
initial doses of 10 mg and are best suited to in-patient use. However, with the
increasing number of elderly patients with atrial fibrillation requiring
anticoagulation, there is a need for a less intense regimen which could be used
for out-patients. We have established such a regimen and report on its
prospective evaluation in 3 7 patients referred for out-patient initiation of
warfarin, and a non-randomized comparison with 37 in-patients, with similar
diagnoses, commenced on a traditional warfarin protocol. After exclusion of five
patients on amiodarone, all of whom experienced supratherapeutic International
Normalized Ratio (INR) results, the new out-patient regimen, employing an initial
5 mg dose, resulted in a lower maximum INR during the first 21 d therapy (median
2.9 v 4.0; P = 0.0001) and fewer INRs >4.5 (2/36 v 9/33) compared to the
traditional 10 mg regimen. Time to reach stable anticoagulation was similar with
each regimen; however, the 5 mg regimen gave a more accurate prediction of
maintenance dose (correlation coefficient for predicted versus actual maintenance
dose, r = 0.985). In comparison to a traditional 10 mg protocol, the proposed 5
mg warfarin induction regimen proved both safer and more reliable for initiation
of prophylactic anticoagulation in patients with atrial fibrillation.
PMID- 9633886
TI - Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary
bypass.
AB - The relative contribution of full-dose aprotinin, used with heparin-bonded
surfaces, to contact activation during cardiopulmonary bypass was examined. In
vitro Carmeda-bonded cardiopulmonary bypass circuits were perfused with whole
blood anticoagulated with heparin (3.3 U/ml). Aprotinin (300 kIU/ml) was added to
the circuits of one set of experiments. Samples were taken prior to perfusion and
at 30, 60, 120 and 360 min. The activated coagulation time was extended in the
aprotinin experiments, significantly at 30 min (P=0.003) and 120 min (P=0.001).
Thrombin-antithrombin complexes and prothrombin fragment F1+2 were both higher in
the non-aprotinin experiments at 120 min (P=0.02 each) and 360 min (P=0.005 and
0.001, respectively). Plasma leucocyte elastase was raised in the non-aprotinin
experiments in comparison to the aprotinin experiments at each timepoint (30 min,
P=0.04; 60 min, P=0.006; 120 min, P=0.001; 360 min, P=0.0001), as was interleukin
8 at 120 min (P=0.05) and 360 min (P=0.0001). No differences were found for the
platelet activation marker P-selectin. Platelet and white blood cell counts fell
significantly in the non-aprotinin experiments compared with the aprotinin
experiments at 360 min (P=0.05 and 0.03, respectively). It would appear that the
use of aprotinin has additional haemostatic beneficial effects to those found
with heparin-bonded circuits in terms of effects on contact activation and
inflammation.
PMID- 9633887
TI - A comparison of artificially-depleted, lyophilized coumarin and fresh coumarin
plasmas in thromboplastin calibration. European Concerted Action on
Anticoagulation.
AB - Artificially-depleted lyophilized plasmas and lyophilized coumarin plasmas were
prepared and compared with fresh coumarin plasmas to assess their comparative
reliability in local thromboplastin calibration using the manual prothrombin time
(PT) technique. Their certified PT values were inserted in turn on the vertical
axis in place of the PT obtained with fresh coumarin plasmas. PT results were
obtained at eight ECAA national laboratories ('test centres') and inserted on the
horizontal axis. The resulting thromboplastin calibration slopes were compared
with conventional fresh coumarin plasma calibration slopes at the same 'test
centres'. When 60 artificially-depleted plasmas were substituted for 60 fresh
plasmas, the mean calibration slopes with the human plain International Reference
Preparation (IRP) were 4.2% higher. For comparison with 20 lyophilized coumarins,
three sets of 20 artificially-depleted plasmas were selected in sequential order
from the 60. The lyophilized coumarin plasmas gave a mean deviation of 9.6% from
the fresh plasma calibration slopes compared with values of 2.0%, 6.1% and 11.7%
for the three sets of 20 depleted plasmas. Although both types of lyophilized
plasma calibration slopes give measurable differences from conventional fresh
plasmas, these may be regarded as acceptable in clinical terms.
PMID- 9633888
TI - Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and
anti-prothrombin antibodies in chronic hepatitis C.
AB - Antiphospholipid antibodies have been demonstrated in chronic hepatitis C, but
their clinical and pathogenetic significance remains elusive. We prospectively
studied 115 patients (85 men, mean age 36.9 years) with chronic hepatitis C
without cirrhosis and treated by alpha-interferon (alpha-IFN). Antiphospholipid
determinations comprised anticardiolipin (ACA), anti-beta2-glycoprotein I and
anti-prothrombin antibodies of the IgG and IgM classes. At entry, 24 patients
(21%) were found to possess low to moderate ACA levels (18 IgG, two IgM and four
both isotypes) compared with only 4/115 age- and sex-matched control subjects
(3.5% P=0.001). ACA positivity rate increased to 31% (P=0.01) after a 6-month
course of alpha-IFN treatment. In contrast, the prevalence of anti-beta2
glycoprotein I and anti-prothrombin antibodies was not significantly different
from controls at either time point. The presence of ACA correlated with that of
antinuclear antibodies (P=0.0002), but was not associated with parameters such as
histological activity, viral burden and response to alpha-IFN, nor with a history
of thrombosis or pregnancy loss. However, a non-significant trend of higher
incidence of mild thrombocytopenia among ACA-positive patients was observed. We
conclude that low-titre ACA positivity is a common finding in patients with
chronic hepatitis C, especially following alpha-IFN treatment, but does not
select a category with different clinical features. These data are in keeping
with the absence of associated anti-beta2GPI and anti-prothrombin antibodies, and
do not support a role for HCV infection in the pathogenesis of the
antiphospholipid syndrome.
PMID- 9633889
TI - Successful use of protease inhibitors in HIV-infected haemophilia patients.
AB - The haemophilias are a group of inherited haemostatic disorders that require
regular clotting factor replacement therapy in the severe and moderately severe
subgroups. Prior to the introduction of adequate viral inactivation methods in
1985, haemophilia patients were at exceptionally high risk of contracting blood
borne viruses from factor concentrates as each batch was derived from the plasma
of thousands of donors. As a result, approximately 60% of these patients were
infected with HIV between 1979 and 1985, and HIV infection now contributes
significantly to the morbidity and mortality seen in this group. Protease
inhibitors (PIs) have been shown to significantly log reduce viral loads and
increase CD4 cell counts in HIV-infected individuals. Recently, there has been
concern about their use in HIV-infected haemophilia patients following increased
bleeding episodes in some patients during PI therapy. We prospectively studied
the effect of PI therapy in 20 HIV-infected haemophilia patients at our centre
over a 6-month period. The mean increase in CD4 cell count was 70 x 10(6)/l and
the mean log decrease in viral load was 1.59 over the study period.
Gastrointestinal side-effects (nausea and vomiting in five, diarrhoea in two)
were the most frequent and resulted in discontinuation of the medication in two
patients. Factor concentrate usage for the group on and off study was similar.
One severe FVIII patient reported a single episode of an unusual bleed which
responded promptly to FVIII concentrate infusion. The significant clinical and
laboratory benefits in terms of HIV disease and the paucity of added bleeding
complications suggest that PI therapy should not be withheld from HIV-infected
haemophilics. Further prospective studies evaluating the efficacy and possible
haemostatic complications related to these promising inhibitors of the HIV
protease are needed.
PMID- 9633890
TI - A common polymorphism in the tumour necrosis factor-alpha gene associated with
high TNF levels is not a risk factor for venous thromboembolism.
AB - The odds ratio of homozygosity or heterozygosity for the TNF2 polymorphism in 575
patients with venous thromboembolism compared to controls was found to be 1.0
(95% CI 0.4-2.1) and 1.1 (95% CI 0.8-1.4) respectively. Comparing subgroups of
patients and controls with the factor V Leiden mutation the odds ratio for the
TNF2 polymorphism was 0.7 (95% CI 0.2-2.2). Despite evidence of a link between
high tumour necrosis factor (TNF) levels and hypercoagulability, our results do
not indicate a link between the genetic regulation of TNF production and venous
thromboembolic disease.
PMID- 9633891
TI - Prevention of central venous catheter associated thrombosis using minidose
warfarin in patients with haematological malignancies.
AB - Thrombosis is a well-recognized complication following insertion of central
venous catheters and is associated with significant morbidity. In an attempt to
reduce line-associated thrombosis, 108 consecutive patients with haematological
malignancies were commenced on prophylactic 'minidose' warfarin, 1 mg/d, at the
time of line insertion. This group of patients were compared with a historic
group of 115 consecutive patients who had not received warfarin. Clinically
suspected venous thrombosis was confirmed by Doppler ultrasound or venography.
Patients taking prophylactic warfarin had their prothrombin time measured three
times per week with the aim of maintaining an INR <1.6. Five (5%) of the 108
patients who received minidose warfarin developed a thrombosis, at a median of 72
d (range 5-166) from the time of catheter insertion. In the 115 patients who were
not anticoagulated 15 (13%) developed a catheter-associated thrombosis at a
median of 16 d (range 1-35). There was a significant reduction in line-associated
thrombosis in patients receiving warfarin (P=0.03). These data suggest that
minidose warfarin reduces the incidence of central venous catheter related
thrombosis in patients with haematological malignancies.
PMID- 9633892
TI - Gain of chromosome 7 marks the progression from indolent to aggressive follicle
centre lymphoma and is a common finding in patients with diffuse large B-cell
lymphoma: a study by FISH.
AB - Gain of chromosome 7 represents one of the most frequent cytogenetic findings in
B-cell lymphomas with a follicular growth pattern. We used fluorescence in situ
hybridization (FISH) and a probe specifying chromosome 7 on lymph node imprints
and/or bone marrow (BM) and peripheral blood (PB) smears from six consecutive
patients with follicle centre lymphomas (FCLs) grade I or II (low-grade
lymphomas), four patients with FCLs grade III and 11 patients with diffuse large
B-cell lymphomas (DLBCLs) (high-grade lymphomas). We found gains of chromosome 7
in 14/18 successfully analysed cases (i.e. 2/6 FCLs grade I-II, 3/3 FLCs grade
III and in 9/9 DLBCLs) using lymph node imprints. Moreover, the FISH technique
demonstrated gains of chromosome 7 in 1/4 BM and 0/4 PB samples from FCLs grade I
II, in 2/4 BM and 2/4 PB specimens from FCLs grade III and in 4/9 BM and 2/9 PB
samples from the DLBCLs. In contrast, morphologically recognizable lymphoma cells
were seen in only 1/4 BM and 0/4 PB samples from the FCLs grade III and in 1/11
BM and 1/11 PB samples from the DLBCLs. We conclude that: (i) gain of chromosome
7 marks the progression from indolent to aggressive FCL and would appear to be a
common finding in patients with FCLs grade III and in DLBCLs, (ii) clonal
lymphoid cells occur frequently in BM and PB in high-grade lymphomas, making
traditional staging by cytomorphology uncertain, and (iii) using gains of
chromosome 7 as a marker of lymphoma cells, FISH is a useful method to detect
minimal residual disease in FCLs grade III and DLBCLs.
PMID- 9633893
TI - Human herpesvirus type 7 in Hodgkin's disease.
AB - Several lines of evidence have pointed to the involvement of a viral agent in the
pathogenesis of Hodgkin's disease (HD). Therefore we investigated the presence of
human herpesvirus type 7 (HHV-7) in 53 cases of HD by polymerase chain reaction
(PCR), DNA in situ hybridization (ISH) and immunohistochemistry. HHV-7 DNA was
frequently detected (68% of the cases) in HD biopsies by PCR independently of the
histological type, whereas only 32% (P<0.05) of positive cases were found in 19
reactive lymph nodes. However, by applying the quantitative PCR technique, the
majority of the samples showed a low level of viral load. Moreover, ISH for HHV-7
DNA was positive in a low number of small T lymphocytes and consistently negative
in Hodgkin and Reed-Sternberg (HRS) cells, which appeared negative for HHV-7 also
at immunohistochemistry. These results indicate that the high frequency of HHV-7
infection in HD: (i) is probably non-productive, (ii) mainly involves small
lymphocytes belonging to the T-lineage, and (iii) is probably due to the
recruitment of non-malignant reactive cells in HD tissue.
PMID- 9633894
TI - Oligoclonal proliferation of human T-cell leukaemia virus type 1 bearing T cells
in adult T-cell leukaemia/lymphoma without deletion of the 3' provirus
integration sites.
AB - We report a new case of an asymptomatic carrier with a deletion of a 3' HTLV-1
integration site. We further investigated whether these 3' deletions of flanking
sequences may explain the oligoclonal pattern of HTLV-1 replication, evidenced by
inverse PCR (IPCR) analysis of tumourous samples from patients with adult T-cell
leukaemia (ATLL). 48 HTLV-1 3' integration sites, derived from tumourous DNA of
five ATLL patients were sequenced. One dominant flanking sequence was obtained in
the four samples harbouring a unique band after Southern-blotting. In one sample,
which harboured two signals after Southern-blotting, IPCR amplification of
diluted tumourous DNA revealed that these two sequences corresponded to one clone
harbouring two integrated proviruses rather than to two distinct cellular clones,
a result consistent with superinfection of the tumourous sample. In addition to
integration sites corresponding to malignant clones, two to six oligoclonal forms
were sequenced in four samples. No flanking sequence homology was found between
clones derived from each patient, indicating that integration sites deletion in
the vicinity of the provirus is a rare event in ATLL. The oligoclonal pattern of
HTLV-1 replication in ATLL may result from clonal expansion of non-malignant HTLV
1-bearing clones within the sample and partly from HTLV-1 superinfection of
monoclonal tumour cells.
PMID- 9633895
TI - Large granular lymphocyte leukaemia occurring after renal transplantation.
AB - Post-transplantation lymphoproliferative disorders (PTLD) are a
clinicopathologically heterogeneous group of lymphoid proliferations. The
majority are of B-cell origin and associated with Epstein-Barr virus (EBV)
infection. In contrast, the development of T-cell PTLD is much less common and
EBV does not appear to be involved in pathogenesis. In this report we describe
three patients who developed large granular lymphocyte (LGL) leukaemia after
renal transplantation. These patients had clonal expansion of CD3+, CD8+, CD57+,
CD56- LGL. We were unable to detect CMV antigen or find evidence for EBV or human
T-cell leukaemia/lymphoma virus genome in the LGL from these patients. These data
show that LGL leukaemia should be included as one of the types of T-cell
proliferations which can occur post transplant.
PMID- 9633896
TI - Clinical characteristics of patients with de novo acute myeloid leukaemia and
isolated trisomy 11: a Cancer and Leukemia Group B study.
AB - Isolated trisomy 11 is the third most common sole trisomy in de novo acute
myeloid leukaemia (AML). However, only 49 cases have been published, and for only
a fraction of these cases has full description of clinical and haematological
features been provided. As a result, little is known about the clinical
characteristics of de novo AML patients with solitary trisomy 11. We have
identified 13 patients (0.9%) with isolated trisomy 11 among a total of 1496
consecutive adult patients successfully karyotyped as part of a prospective
Cancer and Leukemia Group B (CALGB) cytogenetic study (CALGB 8461). Nine patients
(69%) were over the age of 60 (range 29-73 years). Eight patients (62%) were
diagnosed with AML of FAB M2 subtype, three patients (23%) had FAB M1 AML and one
patient each had AML of FAB M0 and M7, respectively. Seven patients (54%) had
high, >100 x 10(9)/l, platelet counts (median 102 x 10(9)/l; range 17-207 x
10(9)/l). All patients received CALGB induction therapy with standard doses of
cytarabine and daunorubicin. Six patients (46%) achieved a complete remission
(CR). The median CR duration was 17.5 months (range 8.7-49.8). Only one patient,
who underwent bone marrow transplantation in first CR, continues in initial CR.
The median survival was 14.3 months (range 0.5-50.7); only one patient survives.
We conclude that de novo AML with isolated trisomy 11 is predominantly associated
with older age, M2 and M1 FAB subtypes, high platelet count and few long-term
disease-free survivals, although it is currently unknown whether isolated trisomy
11 constitutes an independent prognostic factor.
PMID- 9633897
TI - Differential constitutive activation between STAT-related proteins and MAP kinase
in primary acute myelogenous leukaemia.
AB - Many cytokines and growth factors stimulate multiple signal transduction pathways
essential for proliferation in human acute leukaemia cells, including a mitogen
activated protein (MAP) kinase pathway and a Janus kinase (JAK)-STAT (signal
transducers and activators of transcription) pathway. We have previously shown
constitutive activation of MAP kinase in approximately 50% of acute myelogenous
leukaemia (AML) samples. Recently, STAT proteins have been reported to be
constitutively activated in 10-20% of AML cases. STAT3 and STAT5 are the main
STAT proteins activated in haemopoietic progenitors in response to cytokines such
as IL-3, GM-CSF, erythropoietin and thrombopoietin. Although the possibility of
STAT1 protein as a substrate for MAP kinase at a serine residue has been
suggested, the cross-talk between STATs and MAP kinase pathways in vivo,
especially in leukaemia cells, remains unknown. We examined the phosphorylation
of STAT 3 and STAT 5 at the tyrosine residues in AML samples in which MAP kinase
activity had already been found. 40/50 primary AML cases (80%) exhibited
constitutive tyrosine phosphorylation of STAT5. Electrophoretic mobility shift
assay showed DNA binding activity of STAT5 correlated with tyrosine
phosphorylation of STAT5. Similarly, with respect to STAT3, 17/23 cases examined
(74%) showed constitutive tyrosine phosphorylation of STAT3. In addition, we
examined the tyrosyl-phosphorylation of STAT5 isoforms, STAT5A and STAT5B, in 20
AML cases, and found selective STAT5B phosphorylation in the absence of STAT5A
phosphorylation in three cases. Furthermore, in certain AML cases, constitutive
activation of MAP kinase and STAT proteins occurred independently. No significant
correlation of MAP kinase activation was observed with either tyrosine
phosphorylation of STAT3/STAT5 or positive DNA binding of STAT proteins. These
results suggest that constitutive activation of STAT proteins occurs commonly and
that the causes of constitutive activation of these two major cascades are
heterogeneous in AML.
PMID- 9633898
TI - Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in
human acute myeloid leukaemia cells.
AB - The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo
has been improved by the synthesis of monosaccharide stable pro-drugs of butyric
acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D
mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O
isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines
HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute
myeloid leukaemia (AML). AML cell maturation was measured by surface antigen
expression, morphology and cytochemistry. Toxicology in mice was also evaluated
(DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and
CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary
AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a
dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by
flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1
and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1
(27%). The persistence of maturative and apoptotic activity in these new pro
drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a
possible use in differentiation therapy of myelodysplastic syndromes and AMLs.
PMID- 9633899
TI - Chemotherapeutic drug-induced apoptosis in human leukaemic cells is independent
of the Fas (APO-1/CD95) receptor/ligand system.
AB - The potential role of the Fas (CD95/APO-1) receptor/ligand system in
chemotherapeutic drug-induced apoptosis was examined in a number of human
leukaemic cell lines. Flow cytometric profiles of doxorubicin-treated HL-60,
K562, U937 and Jurkat cells failed to show any significant increase in Fas or Fas
ligand expression over 24 h, despite the induction of significant levels of
apoptosis in these cells. Although preincubation of human leukaemic cells with a
neutralizing anti-Fas IgG antibody blocked anti-Fas IgM-induced apoptosis, this
strategy failed to inhibit chemotherapeutic drug-induced apoptosis. To determine
whether recruitment of the Fas/Fas ligand complex during drug-induced apoptosis
was a cell-specific event we utilized the CEM cell line. Doxorubicin treatment of
CEM cells over 24 h failed to show any up-regulation in Fas or Fas ligand protein
levels as detected by flow cytometry. Furthermore, neutralizing anti-Fas IgG Ab
failed to inhibit chemotherapeutic drug-induced apoptosis in CEM cells. The
present studies do, however, demonstrate a role for anti-Fas IgM Ab in producing
a cytotoxic synergistic effect when used in combination with chemotherapeutic
drugs. Low-dose anti-Fas IgM treatment in combination with doxorubicin,
methotrexate, camptothecin and etoposide produced an augmented cytoxicity in CEM
cells. Taken together these observations demonstrate that although recruitment of
the Fas/APO-1/CD95 receptor/ligand system is not a necessary requirement for
chemotherapeutic drug-induced apoptosis, combination of anti-Fas IgM and drug
treatment produces a synergistic cytotoxic effect which may prove useful in the
treatment of human leukaemias.
PMID- 9633900
TI - Evidence for a critical role of DNA topoisomerase IIalpha in drug sensitivity
revealed by inducible antisense RNA in a human leukaemia cell line.
AB - To examine the role of human DNA topoisomerase IIalpha (topo IIalpha) in drug
resistance, we selectively inhibited topo IIalpha gene expression in U937 human
monocytic leukaemia cells stably transfected with a plasmid that allowed for Zn
mediated conditional expression of a human alpha-topo IIalpha antisense sequence.
Expression of topo IIalpha mRNA was reduced to <30%, whereas no significant
alteration of topo IIbeta mRNA expression was observed. Under these conditions,
drug sensitivity to the topo-II-directed agents, etoposide and daunorubicin, was
reduced to approximately 50%, whereas sensitivity to 4-hydroperoxy
cyclophosphamide (4-HC) was not altered. This suggests that a reduced amount of
topo IIalpha mRNA may be sufficient for the resistance to topo II inhibitors in
leukaemia cells.
PMID- 9633901
TI - Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in
patients with chronic myeloid leukaemia during interferon-alpha therapy.
AB - There is a need for fast and sensitive methods to evaluate the response of
patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha)
therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome
positive metaphases. We have used interphase FISH (fluorescence in situ
hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain
reaction) techniques for detection of BCR-ABL-positive cells to measure
suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML
patients undergoing IFN-alpha treatment. Interphase FISH analysis of the
malignant clone in bone marrow using BCR and ABL probes was found to be highly
correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR
quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of
concordance with the proportion of Ph-positive metaphases (r = 0.93). In
addition, the degree of cytogenetic response did not influence the equivalence
between karyotype analysis and molecular methods. We concluded that interphase
FISH and competitive RT-PCR provide reliable information on residual tumour
burden and response to IFN-alpha in CML patients. These molecular methods may
significantly improve the efficiency of residual disease monitoring during IFN
alpha therapy of CML.
PMID- 9633902
TI - Methylation of the p16INK4A gene in multiple myeloma.
AB - The p16INK4A (p16) binds to both cyclin D-CDK4 and cyclin D-CDK6 and inhibits the
progression of the cell cycle from G1 to S phase. Loss of expression of this
protein can occur by several mechanisms including structural alterations. Recent
studies have suggested that the loss of expression of p16 can occur by
hypermethylation of the gene. The methylation status of the p16 gene in multiple
myeloma was examined in three myeloma cell lines (U266, RPMI8226 and IM9) and 16
primary myeloma samples using methylation-specific polymerase chain reaction
(MSP). The U266 and RPMI8226 cell lines contained a completely methylated p16
gene and the IM9 line had a partially methylated p16 gene. Identical results were
obtained by another polymerase chain reaction (PCR)-based methylation assay
system as well as Southern blotting after using a methylation-sensitive
restriction enzyme. The U266 cell line expressed no p16, and the IM9 had weak
expression as determined by reverse transcript (RT-)PCR. The U266 cells began to
express, and IM9 increased the accumulation of, the p16 RNA after treatment with
the demethylating agent 5'-aza-2-deoxycytidine (10(-6)-10(-5) M). This suggested
that the levels of methylation of the p16 gene detected by the MSP technique
correlated with the regulation of transcription of this gene. Examination of the
primary myeloma samples showed that eight of 16 (50%) contained a methylated p16
gene. We have previously found that alterations of the p16 gene, such as
deletions and point mutations, are rare in primary multiple myeloma; none of the
16 samples included in this study had p16 gene alterations. Our results suggest
that methylation of the p16 gene may contribute to the development and/or
progression of multiple myeloma.
PMID- 9633903
TI - Specific depletion of alloreactive T cells in HLA-identical siblings: a method
for separating graft-versus-host and graft-versus-leukaemia reactions.
AB - Accumulating evidence indicates that alloreactive donor T cells confer both graft
versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following
allogeneic bone marrow transplantation. We have developed a method to deplete
alloreactive donor T cells with an immunotoxin targeting the alpha chain of the
IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical
sibling donors, we measured donor helper T-lymphocyte precursor frequencies
(HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus
host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC,
before and after the depletion. In seven pairs there was a 4.3-fold reduction of
donor-versus-host HTLPf (P=0.017), without a significant change in the donor
frequencies against third party (P=0.96). In eight further donor-recipient pairs,
immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000
before and 1/839,000 after depletion, P=0.007). There was a smaller non
significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to
1/334,000 (P=0.19). These results suggest that selective T-cell depletion can
significantly deplete donor anti-host reactivity while conserving anti-leukaemia
reactivity in HLA-matched donor-recipient pairs.
PMID- 9633904
TI - Haemopoietic defect and decreased expansion potential of bone marrow autografts
from patients with acute myeloid leukaemia in first remission.
AB - Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in
complete remission (CR) is frequently followed by a slow haemopoietic recovery.
We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and
progenitor cell (CD34+ DR+) populations from patients with AML in CR, and
compared these data with those of normal BM. The feasibility of ex vivo expansion
in stroma-conditioned medium supplemented with cytokines was also investigated.
The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased
compared to normal, whereas these values were similar to normal for CD34+ DR+
cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and
CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction
was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was
poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed
for patient cells. LTC-IC were below the level of detection after 14-21 d of
expansion culture of CD34+ DR- patient cells, whereas they were variably
maintained or expanded for normal cells. After expansion culture, cytogenetic
and/or FISH analyses did not reveal the anomalies present at diagnosis,
regardless of the cell subpopulation analysed. In conclusion, BM cells of
patients with AML in CR show a profound defect at the level of a stem cell
enriched population. No meaningful ex vivo expansion could be obtained in culture
conditions allowing for a significant expansion from a normal stem cell
population.
PMID- 9633905
TI - The dose of granulocyte colony-stimulating factor administered following
cytotoxic chemotherapy is not related to the rebound level of circulating CD34+
haemopoietic progenitor cells during marrow recovery.
AB - We report on the RmetHuG-CSF (filgrastim)-related mobilization efficiency in 120
patients with multiple myeloma who received cytotoxic chemotherapy. Three
schedules of G-CSF administration starting 24h after the end of chemotherapy were
used: (1) a standard dose of 300 microg/d until the completion of PBSC
collection; (2) dose escalation from 300 to 600-1200 microg/d during marrow
recovery; (3) 600 or 1200 microg/d starting 24 h after cytotoxic chemotherapy. As
a result, the individual dose per kg bodyweight varied between 2.83 and 23.08
microg. No relationship was found between the dose of G-CSF administered and the
peak level of circulating CD34+ cells or the CD34+ cell counts recorded over the
entire collection period.
PMID- 9633906
TI - Mutation analysis by a non-radioactive single-strand conformation polymorphism
assay in nine families with X-linked severe combined immunodeficiency (SCIDX1).
AB - X-linked severe combined immunodeficiency (SCIDX1) is an inherited disease
characterized by profound abnormalities of cell-mediated and humoral immunity.
Patients with SCIDX1 have defects in the common cytokine receptor gamma chain
gene (IL2RG) that encodes a shared, essential component of the receptors for
interleukin-2 (IL-2), IL-4, IL-7, IL-9 and IL-15. We have characterized nine
SCIDX1 families by using a DNA-based, non-radioactive screening method and DNA
sequencing. Nine different mutations were found, scattered from exon 1 to exon 5
of the IL2RG gene. Two of these mutations have been previously identified in
other unrelated patients; the other seven are novel mutations that differ from
all of the 95 already reported in the IL2RG mutation data base. In addition to
describing novel mutations in the IL2RG gene, this study shows that the knowledge
of the genetic defect and the use of an efficient, non-radioactive, and rapid
screening approach have important implications for prenatal and postnatal
diagnosis, carrier female identification, and possibly prenatal therapy.
PMID- 9633907
TI - Intravenous immunoglobulin therapy and renal dysfunction.
PMID- 9633908
TI - Infectious complications after CD34-selected autologous peripheral blood stem
cell transplantation.
PMID- 9633909
TI - Screening for factor V Leiden and a prothrombin gene polymorphism in patients
with Glanzmann's thrombasthenia.
PMID- 9633910
TI - G-CSF after PBSC transplantation.
PMID- 9633911
TI - Methotrexate therapy to alleviate anaemia in a patient with large granular
lymphocytosis.
PMID- 9633912
TI - Apoptosis: basic mechanisms and implications for cardiovascular disease.
PMID- 9633913
TI - Role of apoptosis in the disappearance of infiltrated and proliferated
interstitial cells after myocardial infarction.
AB - Myocardial infarction (MI) progresses from the acute death of myocytes and the
infiltration of inflammatory cells into granulation, followed by scars. During
the healing process, the myocardial interstitial cell population in the infarcted
tissues increases markedly and then decreases. We postulated that apoptosis is
responsible for this process. Twenty-four male Japanese white rabbits underwent a
30-minute occlusion of the left coronary artery followed by reperfusion for 2
days, 2 weeks, or 4 weeks (n=8 each). The histological features consisted of dead
cardiomyocytes and marked leukocyte infiltration at 2 days after MI and
granulation consisting of numerous alpha-smooth muscle actin-positive
myofibroblasts, macrophage antigen-positive macrophages, and neovascularization
at 2 weeks. At 4 weeks, the cellularity decreased markedly, and scars were
evident. Interstitial cells with positive nick end labeling were significantly
more frequent at the light microscopic level in the 2-day MI samples (5.3+/-3.6%
in the center and 6.9+/-3.3% in the periphery of the infarct region) than in the
2-week (2.5+/-1.0%) and 4-week (0.5+/-0.5%) samples. DNA electrophoresis showed a
clear ladder in tissues from the ischemic areas at 2 days after MI but not at 2
and 4 weeks after MI. Ultrastructurally, typical apoptotic figures, including
apoptotic bodies and condensed nuclei without ruptured plasma membranes, were
detected in leukocytes from all hearts with 2-day MI and in myofibroblasts,
endothelial cells, and macrophages from all hearts with 2-week MI. In the
electron microscopic in situ nick end labeling, immunogold particles intensely
labeled the condensed chromatin of the typical apoptotic nuclei. These particles
were also accumulated on nuclei of the interstitial cells showing homogeneous
density but not definite condensation as typical apoptotic nuclei, suggesting an
early stage of apoptosis. Thus, apoptosis plays an important role in the
disappearance of both the infiltrated leukocytes and the proliferated
interstitial cells after MI. This finding may have therapeutic implications for
postinfarct ventricular remodeling through apoptosis handling during the healing
stage of MI.
PMID- 9633914
TI - Effect of vacuolar proton ATPase on pHi, Ca2+, and apoptosis in neonatal
cardiomyocytes during metabolic inhibition/recovery.
AB - Recently, we found that vacuolar proton ATPase (VPATPase) operates in
cardiomyocytes as a complementary proton-extruding mechanism. Its activity was
increased by preconditioning with resultant attenuation of intracellular
acidification during ischemia. In this study, we examined whether VPATPase
mediated proton efflux during metabolic inhibition/recovery may spare Na+
overload via Na+-H+ exchange, attenuate Na+-Ca2+ exchange, and decrease
apoptosis. Neonatal rat cardiomyocytes were subjected to 2- to 3-hour metabolic
inhibition with cyanide and 2-deoxyglucose and 24-hour recovery. The effect of
VPATPase inhibition by 50 nmol/L bafilomycin A1 on apoptosis, pHi, and [Ca2+]i
was studied by flow cytometry with propidium iodide, seminaphthorhodafluor
(SNARF)-1-AM, and indo-1-AM staining, respectively. VPATPase inhibition increased
the amount of apoptosis measured after 24 hours of recovery and abrogated the
protective effect of inhibition of Na+-H+ exchange by (5-N-ethyl-N
isopropyl)amiloride (EIPA). Dual blockade of VPATPase and Na+-H+ exchange was
additive in effect with EIPA on pHi during metabolic inhibition/recovery and
recovery from the acid challenge with sodium propionate. VPATPase blockade
increased the rate of accumulation of intracellular Ca2+ at the beginning of
metabolic inhibition and abrogated the delaying effect of EIPA on intracellular
Ca2+ accumulation. These results indicate that VPATPase plays an important
accessory role in cardiomyocyte protection by reducing acidosis and Na+-H+
exchange-induced Ca2+ overload.
PMID- 9633915
TI - Angiotensin II stimulation in vitro induces hypertrophy of normal and
postinfarcted ventricular myocytes.
AB - To determine whether angiotensin II (Ang II) stimulation of adult ventricular
myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume
and protein content per cell were examined by confocal microscopy. Moreover, the
possibility was considered that the upregulation of Ang II receptors on myocytes
after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth.
Left ventricular myocytes isolated from control and failing hearts 3 days after
infarction were cultured for 3 and 7 days in the presence of Ang II. Normal
myocytes did not show an increase in volume and protein content at 3 days, but a
16% and 20% increase in these respective parameters was found at 7 days. Cell
growth was faster and greater in myocytes from postinfarcted hearts. In these
cells, myocyte volume increased 23% and protein content increased 28% at 3 days
after Ang II administration. The higher hypertrophic reaction of myocytes from
infarcted hearts occurred in spite of a 19% larger volume at isolation. In both
groups of myocytes, the AT1 receptor blocker losartan completely inhibited the
consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no
effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte
growth through the activation of AT1 receptors, which modulate the time and
magnitude of this cellular response.
PMID- 9633916
TI - Beta1 integrins participate in the hypertrophic response of rat ventricular
myocytes.
AB - Multiple signaling pathways have been implicated in the hypertrophic response of
ventricular myocytes, yet the importance of cell-matrix interactions has not been
extensively examined. Integrins are cell-surface molecules that link the
extracellular matrix to the cellular cytoskeleton. They can function as cell
signaling molecules and transducers of mechanical information in noncardiac
cells. Given these properties and their abundance in cardiac cells, we evaluated
the hypothesis that beta1 integrin function is involved in the alpha1-adrenergic
mediated hypertrophic response of neonatal rat ventricular myocytes. The
hypertrophic response of this model required interaction with extracellular
matrix proteins. Specificity of these results was confirmed by demonstrating that
ventricular myocytes plated onto an anti-beta1 integrin antibody supported the
hypertrophic gene response. Adenovirus-mediated overexpression of beta1 integrin
augmented the myocyte hypertrophic response when assessed by protein synthesis
and atrial natriuretic factor production, a marker gene of hypertrophic
induction. DNA synthesis was not altered by integrin overexpression. Transfection
of cultured cardiac myocytes with either the ubiquitously expressed beta1A
integrin or the cardiac/skeletal muscle-specific beta1 isoform (beta1D) activated
reporter expression from both the atrial natriuretic factor and myosin light
chain-2 ventricular promoters, genetic markers of ventricular cell hypertrophy.
Finally, suppression of integrin signaling by overexpression of free beta1
integrin cytoplasmic domains inhibited the adrenergically mediated atrial
natriuretic factor response. These findings show that integrin ligation and
signaling are involved in the cardiac hypertrophic response pathway.
PMID- 9633917
TI - Increased protein kinase C activity in myotrophin-induced myocyte growth.
AB - Myotrophin, a novel protein that has been shown to stimulate myocyte growth, has
been isolated, purified, and sequenced from the hearts of spontaneously
hypertensive rats and dilated cardiomyopathic human tissue. Recently, the cDNA
clones encoding myotrophin have been isolated and expressed in Escherichia coli,
and the recombinant myotrophin was found to be as biologically and
immunologically active as natural myotrophin. The mechanism by which myotrophin
stimulates protein synthesis and initiates myocardial hypertrophy is not known.
To evaluate the involvement of protein kinase C (PKC) in myotrophin-induced
hypertrophy, PKC activity and its distribution in the subcellular fraction were
determined in cultured neonatal and adult myocytes. PKC activity was determined
by measuring the incorporation of 32P into histone type III-S and PKCepsilon
substrate peptide (epsilon(pep)) from [gamma-32P]ATP in neonatal myocytes.
Myotrophin significantly stimulated PKC activity in neonatal myocytes and was
associated with a significant increase in protein synthesis. The effect of
myotrophin on the stimulation of PKC activity and [3H]leucine incorporation was
abolished by pretreatment with either staurosporine or H-7, two selective,
pharmacological PKC inhibitors. Pretreatment of myocytes with staurosporine also
reduced the myotrophin-induced mRNA levels of c-fos and beta-myosin heavy chain.
To evaluate the subcellular events whose occurrence was due to myotrophin and
translocation of PKC, we studied the effect of genistein, a tyrosine kinase
inhibitor, on myotrophin-induced neonatal myocyte growth. Genistein attenuated
the [3H]leucine incorporation induced by myotrophin. To define the specificity of
the PKC isoform(s) involved in myotrophin-stimulated myocyte growth, both
neonatal and adult myocytes were treated with myotrophin, and Western blot
analyses were performed by using the antibodies of different PKC isoforms.
Results showed that both PKCalpha and PKCepsilon isoforms participated in the
myotrophin-induced neonatal myocyte growth, whereas only the PKCepsilon isoform
was involved in myotrophin-induced adult myocyte hypertrophy. PKCdelta and
PKCzeta do not seem to participate in either neonatal or adult myocyte growth
induced by myotrophin. Treatment with antisense oligonucleotides specific for
PKCalpha and PKCepsilon isoforms further supported this result. PKCalpha is the
major PKC isoform in neonatal myocytes and needs Ca2+ and phospholipids for its
activation, and PKCepsilon (the Ca2+-independent PKC isoform) is present in both
neonatal and adult myocytes; the 15-mer antisense oligodeoxynucleotides of each
were used for this study. Treatment of neonatal myocytes with the PKCalpha and
PKCepsilon antisense oligodeoxynucleotides for 5 days significantly reduced Ca2+
dependent and Ca2+-independent PKC activity, respectively, as well as the
[3H]leucine incorporation induced by myotrophin. Furthermore, myotrophin-induced
PKC activity was primarily located in the particulate fraction and did not result
in a concomitant decrease in the cytosolic fraction. Myotrophin does not change
PKC isoform expression (both Ca2+ dependent and independent PKC isoforms used in
this study) in rat neonatal cardiac fibroblasts. Our data suggest that myotrophin
exerts its action on protein synthesis, possibly through a tyrosine kinase
coupled pathway and translocation of PKC from the cytosol to the cell membrane.
PMID- 9633918
TI - Regulation of mitochondrial [NADH] by cytosolic [Ca2+] and work in trabeculae
from hypertrophic and normal rat hearts.
AB - Pressure overload hypertrophy has previously been shown to reduce contractility
but paradoxically to increase O2 consumption rates at a given force. Because O2
consumption rates are related to mitochondrial [NADH] ([NADH]m), we tested the
hypothesis that with hypertrophy, control of [NADH]m may be altered. Left
ventricular trabeculae were isolated from banded and control rat hearts, and
fluorescence spectroscopy was used to monitor [NADH]m and cytosolic [Ca2+]
([Ca2+]c). The hearts from banded rats developed hypertrophy (heart-to-body
weight ratio increased from 4.1+/-0.1 to 4.9+/-0.1 mg/g) and hypertension
(systolic arterial pressure increased from 117+/-4 to 175+/-5 mm Hg). Muscle
workload was increased by stepwise increases in pacing frequency (up to 2 Hz).
After increased work, [NADH]m fell and then slowly recovered toward control
levels. When work was decreased, [NADH]m overshot control values and then slowly
returned. The Ca2+-independent initial fall was larger for trabeculae from rats
with hypertrophied hearts than from control rats (eg, 17+/-2% versus 11+/-1% when
work was increased by increasing the frequency from 0.25 to 1 Hz). At 1 Hz,
average [Ca2+]c was approximately 280 nmol/L, and the Ca2+-dependent [NADH]m
recovery was larger for trabeculae from rats with hypertrophied hearts (17+/-4%
versus 10+/-2%) despite similar average [Ca2+]c. At steady state after Ca2+
dependent recovery, there was no difference in [NADH]m (fall of 1+/-2% versus 1+/
1%). Furthermore, the Ca2+-dependent overshoot was larger for trabeculae from
hypertrophied than from control hearts (increase of 14+/-2% versus 9+/-2% when
frequency was decreased from 1 to 0.25 Hz). We conclude that (1) there is
initially a larger imbalance in NADH production versus consumption rate in
hypertrophy (because NADH fell more) and (2) the Ca2+-dependent recovery
mechanism is enhanced in hypertrophy (because NADH recovered and overshot more),
thus compensating for the larger imbalance.
PMID- 9633919
TI - Ineffective perfusion-contraction matching in conscious, chronically instrumented
pigs with an extended period of coronary stenosis.
AB - Several models purported to represent hibernating myocardium involve a coronary
stenosis (CS) to reduce blood flow (BF) and function without eliciting necrosis
in anesthetized pigs. The goal of the present study was to determine whether
sustained moderate reduction in coronary BF in conscious pigs induced hibernating
myocardium, ie, perfusion-contraction matching with no necrosis. These
experiments were conducted in conscious pigs chronically instrumented with a
coronary artery BF probe and hydraulic occluder, left ventricular (LV) pressure
gauge, and wall thickening (WT) crystals in the potentially ischemic and
nonischemic zones. The hydraulic occluder was inflated to induce a stable 41+/-4%
reduction in BF for 24 hours. Ischemic zone systolic WT fell initially with CS
and then continued to decline during the period of CS even though blood flow did
not change further, suggesting the induction of myocardial stunning. At 2 days
after release of CS, WT was still depressed by 48+/-15%. Assessment of necrosis
by histology or triphenyltetrazolium chloride showed 40+/-5% multifocal patchy
necrosis interspersed with normal tissue involving the inner one third to one
half of the ventricular wall. Regional myocardial BF (radioactive microsphere
technique) was assessed by dividing the entire LV into an average of 488+/-59
pieces and examining the spatial distribution of BF within the area at risk
(AAR). BF in the samples in the area of patchy necrosis was reduced (-66+/-4%
from a baseline of 1.55+/-0.27 mL x min(-1) x g(-1)), whereas BF was maintained
in samples in the AAR without necrosis (-2+/-7% from a baseline of 1.25+/-0.22 mL
x min(-1) x g(-1)). These findings indicate that when hypoperfusion induced by CS
in conscious pigs is sustained, the result is necrosis rather than hibernating
myocardium. The remainder of the AAR, which lacked necrosis, might have been
mistaken for hibernating myocardium had only histology been evaluated and BF not
been measured and found to be at normal levels.
PMID- 9633920
TI - Simulation study of cellular electric properties in heart failure.
AB - Patients with severe heart failure are at high risk of sudden cardiac death. In
the majority of these patients, sudden cardiac death is thought to be due to
ventricular tachyarrhythmias. Alterations of the electric properties of single
myocytes in heart failure may favor the occurrence of ventricular arrhythmias in
these patients by inducing early or delayed afterdepolarizations. Mathematical
models of the cellular action potential and its underlying ionic currents could
help to elucidate possible arrhythmogenic mechanisms on a cellular level. In the
present study, selected ionic currents based on human data are incorporated into
a model of the ventricular action potential for the purpose of studying the
cellular electrophysiological consequences of heart failure. Ionic currents that
are not yet sufficiently characterized in human ventricular myocytes are adopted
from the action potential model developed by Luo and Rudy (LR model). The main
results obtained from this model are as follows: The action potential in
ventricular myocytes from failing hearts is longer than in nonfailing control
hearts. The major underlying mechanisms for this prolongation are the enhanced
activity of the Na+-Ca2+ exchanger, the slowed diastolic decay of the [Ca2+]i
transient, and the reduction of the inwardly rectifying K+ current and the Na+-K+
pump current in myocytes of failing hearts. Furthermore, the fast and slow
components of the delayed rectifier K+ current (I(Kr) and I(Ks), respectively)
are of utmost importance in determining repolarization of the human ventricular
action potential. In contrast, the influence of the transient outward K+ current
on APD is only small in both cell groups. Inhibition of I(Kr) promotes the
development of early afterdepolarizations in failing, but not nonfailing,
myocytes. Furthermore, spontaneous Ca2+ release from the sarcoplasmic reticulum
triggers a premature action potential only in failing myocytes. This model of the
ventricular action potential and its alterations in heart failure is intended to
serve as a tool for investigating the effects of therapeutic interventions on the
electric excitability of the human ventricular myocardium.
PMID- 9633921
TI - Complement gene expression by rabbit heart: upregulation by ischemia and
reperfusion.
AB - Activation of the complement system has been implicated in the pathogenesis of
myocardial ischemia/reperfusion injury. It has always been assumed that liver is
the primary source of complement components. In the present study, we used the
reverse-transcriptase polymerase chain reaction technique to establish that the
mRNAs for complement proteins C3 and C9 are expressed in rabbit heart. Rabbit
liver, brain, spleen, and kidney were also shown to express C3 and C9 mRNAs. We
used Western blotting to establish that these mRNAs in heart are translated into
the corresponding proteins. We further established that dramatic upregulation of
the mRNAs occurred in Langendorff-perfused isolated hearts subjected to ischemia
and reperfusion. C3 mRNA was always expressed at higher levels than was C9 mRNA,
but C9 mRNA showed greater upregulation under stress. Compared with levels in
control hearts subjected to 5 minutes of normoxic perfusion, hearts subjected to
0.5 hours of ischemia followed by 1 hour of reperfusion had a 4.72-fold increase
in C3 mRNA and a 19.5-fold increase in C9 mRNA. By contrast, C3 mRNA in hearts
subjected to 3.5 hours of normoxic perfusion showed no change, and those
subjected to 3.5 hours of ischemia showed only a 1.72-fold increase, whereas C9
mRNA levels increased by 5.17-fold after 3.5 hours of normoxic perfusion and 12.5
fold after 3.5 hours of ischemia. The results of this study demonstrate for the
first time that heart tissue is capable of expressing genes and proteins of the
complement system, although it is not yet known which cell types are responsible.
They further demonstrate that ischemia and reperfusion of the heart promotes a
rapid upregulation of the mRNAs encoding the complement proteins C3 and C9 and
that these abnormal levels considerably exceed those of normal liver. These
observations are consistent with the hypothesis that local production of
complement proteins may contribute significantly to the degree of ischemic injury
to the myocardium and that complement expression is augmented by reperfusion.
PMID- 9633922
TI - Myocyte cell death in the diseased heart.
PMID- 9633923
TI - Development of compartmental models in stable-isotope experiments: application to
lipid metabolism.
AB - Kinetic experiments are of great importance in lipid research because they
further the understanding of lipid metabolism in vivo and help to explain the
physiopathology of lipid disorders in humans. At present, due to species
specificity, no valid animal model can efficiently replace a study in humans to
explore lipid metabolism, and the use of radioactive tracers is restricted in
humans. Thus, stable-isotope tracer kinetic studies have become an important
component of research programs to achieve in humans a quantitative understanding
of the dynamics of metabolic processes in vivo. The aim of this review is to
describe the practical aspects of compartmental model development in stable
isotope experiments. The recent development of computer hardware and modeling
software has dramatically facilitated the task of the modeler in his or her
calculations. In the current review, we show that the model may be considered an
integral component of the experimental design and that model development must
obey strict rules to provide a rigorous solution. The main difficulties of model
development in tracer experiments, such as experiment design, model
identifiability, data expression, comparison of models, or tracer recycling, are
presented with extensive references. We have paid particular attention to kinetic
modeling in stable-isotope experiments because they have shown the greatest
development in recent years.
PMID- 9633924
TI - HDL3-mediated inhibition of thrombin-induced platelet aggregation and fibrinogen
binding occurs via decreased production of phosphoinositide-derived second
messengers 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate.
AB - We demonstrate that physiological concentrations of HDL3 inhibit the thrombin
induced platelet fibrinogen binding and aggregation in a time- and concentration
dependent fashion. The underlying mechanism includes HDL3-mediated inhibition of
phosphatidylinositol 4,5-bis-phosphate turnover, 1,2-diacylglycerol and inositol
1,4,5-tris-phosphate formation, and intracellular calcium mobilization. The
inhibitory effects of HDL3 on inositol 1,4,5-tris-phosphate formation and
intracellular calcium mobilization were abolished after covalent modification of
HDL3 with dimethylsuberimidate. Furthermore, they could be blocked by calphostin
C and bis-indolylmaleimide, 2 highly selective and structurally unrelated protein
kinase C inhibitors. However, the inhibitory effects of HDL3 were not blocked by
H89, a protein kinase A inhibitor. In addition, HDL3 failed to induce cAMP
formation but stimulated the phosphorylation of the protein kinase C 40- to 47-kD
major protein substrate. We observed a close temporal relationship between the
HDL3-mediated inhibition of thrombin-induced inositol 1,4,5-tris-phosphate
formation, intracellular calcium mobilization, and fibrinogen binding and the
phosphorylation of the protein kinase C 40- to 47-kD major protein substrate.
Taken together, these findings indicate that the HDL3-mediated inhibition of
thrombin-induced fibrinogen binding and aggregation occurs via inhibition of
phosphatidylinositol 4,5-bis-phosphate turnover and formation of 1,2
diacylglycerol and inositol 1,4,5-tris-phosphate. Protein kinase C may be
involved in this process.
PMID- 9633925
TI - Relationship between plasma viscosity and the severity of coronary heart disease.
AB - Several studies have indicated that plasma viscosity contributes to
cardiovascular risk in men. So far, a significant relationship between plasma
viscosity and the severity of coronary heart disease has not been found. Thus,
the present study is the first to report on the relationship of plasma viscosity
and the severity of coronary heart disease. In a collective of 1142 male
myocardial infarction patients, plasma viscosity and additional laboratory
parameters were determined. Atherosclerotic changes were quantified by coronary
angiography. Patients were divided into groups without any, and with one to three
stenosed vessels. We found a positive relationship between plasma viscosity and
the severity of coronary heart disease, even after adjusting groups for age,
fibrinogen, and use of diuretics. Mean plasma viscosity ranged from 1.141+/-0.035
mPa s in patients without stenosed vessels to 1.162+/-0.044 mPa s in patients who
had three coronary vessels with stenoses >50%. Differences between the groups
were significant (P<0.001 to 0.05), with two exceptions: differences between
patients without any and with one stenosed vessel, as well as between patients
with one and two stenosed vessels, did not reach the significance level. On the
whole, we can give further support to the hypothesis that cardiovascular risk
factors and coronary heart disease may be linked by plasma viscosity.
PMID- 9633926
TI - Sialic acid content of LDL in coronary artery disease: no evidence of
desialylation in subjects with coronary stenosis and increased levels in subjects
with extensive atherosclerosis and acute myocardial infarction: relation between
desialylation and in vitro peroxidation.
AB - We recently showed that sialic acid content of LDL was not a marker of early
cardiovascular disease (Arterioscler Thromb Vasc Biol. 1995;15:334-339). Here, we
investigated this parameter in patients with advanced coronary artery disease
(CAD). We first examined 100 patients having undergone coronary angiography. The
distribution of LDL sialic acid values was very similar in subjects with no
coronary stenosis (31.3+/-3.7 nmol/mg LDL protein, mean+/-SD) and those with > or
= 75% stenosis in at least one main coronary artery or > or = 50% stenosis in at
least two main coronary arteries (32.1+/-5.5 nmol/mg LDL protein). In contrast,
LDL sialic acid content was significantly increased in patients with both
coronary stenosis and peripheral arterial atherosclerotic lesions compared with
those with either no lesion or only one or the other type of lesion. We then
examined LDL sialic acid content in 20 patients with acute myocardial infarction.
LDL sialic acid content was significantly higher (35.9+/-3.2 nmol/mg LDL protein)
than that in the CAD(-) control group. These data suggest that LDL sialic acid
content increases with the extension of atherosclerosis and its progression to
acute complications. To explain the discordance with Orekhov and coworkers
(Atherosclerosis. 1991;86:153-161), who showed that LDL sialic acid content in
patients with advanced CAD was lower than that in healthy subjects, we studied
the time courses of sialic acid, TBARS, and vitamin E levels in LDL dialyzed in
different experimental conditions. A continuous decrease in both sialic acid and
vitamin E levels and an increase in TBARS levels were observed in LDL samples
containing less than 1 mmol/L EDTA, the intensity and rapidity of which varied
with the EDTA concentration in the buffer. Our data support the idea that
desialylation may result from in vitro peroxidation of LDL.
PMID- 9633927
TI - An animal model to study local oxidation of LDL and its biological effects in the
arterial wall.
AB - Oxidized LDL (oxLDL) is present in atherosclerotic lesions and is believed to
play a key role in atherogenesis. Mainly on the basis of cell culture studies,
oxLDL has been shown to produce many biological effects that influence the
atherosclerotic process. To study LDL oxidation in vivo, we have established a
model in which Sprague-Dawley rats are given a single injection of unmodified
human LDL (> or = 4 mg/kg body weight). Within 6 hours, an accumulation of
apolipoprotein B and epitopes present on oxLDL are detected in the arterial
endothelium and media. The presence of oxLDL is associated with activation of the
transcription factor nuclear factor-kappaB in the endothelium as well as
endothelial expression of intercellular adhesion molecule-1. Injection of LDL
enriched with the antioxidant probucol resulted in arterial accumulation of
apolipoprotein B, but the expression of oxLDL-specific epitopes was reduced at 24
hours. Thus, this simple model has the potential to analyze the mechanisms behind
and biological effects of LDL oxidation in vivo.
PMID- 9633928
TI - Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic
and activating factor/monocyte chemoattractant protein-1 in human endothelial
cells.
AB - In vivo, vascular walls are exposed to mechanical stretch, which may promote
atherogenesis. This study was designed to investigate the effect of mechanical
stretch on the production and gene expression of cytokines in endothelial cells
(ECs) of human umbilical veins. ECs were cultured on flexible silicone membranes
and exposed to cyclic mechanical stretch. Although the secretion levels of
interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, granulocyte (G)
colony stimulating factor (CSF), G and macrophage (M) -CSF, and M-CSF were not
affected by cyclic stretch over 24 hours, the levels of IL-8 and monocyte
chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP
1) were significantly increased by cyclic stretch. Northern blot analysis
indicated that the mRNA levels of IL-8 and MCAF/MCP-1 were upregulated by cyclic
stretch as a function of its intensity. Cytochalasin D, which disrupts the actin
cytoskeleton, abolished the stretch-induced gene expression of IL-8 and MCAF/MCP
1. In contrast, neither inhibition of stretch-activated ion channels nor
disruption of microtubules affected the induction of these chemokines by cyclic
stretch. Northern blot analysis using enzyme inhibitors showed that phospholipase
C, protein kinase C, and tyrosine kinase were involved in the stretch-induced
gene expression of IL-8 and MCAF/MCP-1, whereas cAMP- or cGMP-dependent protein
kinase was not. In conclusion, cyclic stretch enhanced the secretion and gene
expression of IL-8 and MCAF/MCP-1 in a stretch-dependent fashion, and the
integrity of the actin cytoskeleton and activities of phospholipase C, protein
kinase C, and tyrosine kinase may be essential in the process of stretch-induced
gene induction of IL-8 and MCAF/MCP-1.
PMID- 9633929
TI - Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a
secondary prevention study of aortic atherosclerosis in ovariectomized
cholesterol-fed rabbits.
AB - The influence of progestogens in combination with 17beta-estradiol (E2) on
cardiovascular disease remains controversial. This study investigated the effect
of norethindrone acetate (NETA) combined with E2 on aortic atherosclerosis.
Eighty mature female rabbits were ovariectomized, then fed a cholesterol-rich
diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were
randomized to four equally large groups for the following 38-week intervention
period. One group received placebo, another group oral E2 4 mg daily (E2), and
the last two groups oral E2 4 mg daily combined with either NETA 1 mg (E2NETA1)
or NETA 3 mg (E2NETA3). The cholesterol intake was reduced to a "maintenance"
level of 80 mg/d during the intervention period. Total serum cholesterol and
ultracentrifuged lipoproteins were analyzed enzymatically throughout the study.
The cholesterol content in the aortic wall was 2.76+/-0.44 micromol/cm2 (mean+/
SEM) in the E2NETA1 group, 1.77+/-0.37 micromol/cm2 in the E2NETA3 group, 5.46+/
0.77 micromol/cm2 in the E2 group, and 7.20+/-0.94 micromol/cm2 in the placebo
group (ANOVA P<0.0001). The difference (in the aortic cholesterol accumulation)
between the E2 and each of the combined E2/NETA groups was statistically
significant (P<0.01) but could only partly be explained by the differences in
serum lipids and lipoproteins. In conclusion, NETA enhances the antiatherogenic
effect of E2 in cholesterol-fed rabbits. This effect is only partially mediated
through changes in serum lipids and lipoproteins.
PMID- 9633930
TI - Inhibition of repetitive thrombus formation in the stenosed canine coronary
artery by enoxaparin, but not by unfractionated heparin.
AB - Experiments were designed to compare the antithrombotic efficacy of enoxaparin
and unfractionated heparin (UH) in a model of platelet-dependent cyclic flow
reductions (CFRs) in the stenosed canine circumflex coronary artery. Low
molecular-weight heparins (LMWHs) are safe and effective in the prevention and
treatment of venous thromboembolism. The present experiments were designed to
evaluate the potential use of LMWHs in arterial thrombotic indications by
comparing the antithrombotic effect of an LMWH with that of UH in an animal model
of unstable angina. After establishment of consistent CFRs by experimentally
induced vascular stenosis and damage, vehicle (saline), enoxaparin, or UH was
administered intravenously as a loading dose plus a continuous infusion for 1
hour. The inhibition of CFRs was taken as an indicator of antithrombotic
efficacy. Enoxaparin inhibited repetitive platelet thrombus formation in a dose
dependent manner, with significant inhibition of CFRs achieved at 0.5 mg/kg + 5
microg/kg per minute. This dose of enoxaparin resulted in anti-Xa levels of 0.9
to 1.0 IU/mL, anti-IIa levels of 0.2 to 0.3 IU/mL, activated partial
thromboplastin time (APTT) of 1.3-fold over baseline, and a 1.4-fold increase
(NS) in template bleeding time. Near-complete abolishment of CFRs was achieved
with enoxaparin at 1.0 mg/kg + 10 microg/kg per minute. This dose of enoxaparin
produced anti-Xa levels of 2 to 2.2 IU/mL, anti-IIa levels of 0.5 to 0.6 IU/mL,
an increase in APTT of 1.4- to 1.5-fold over baseline, and a 1.9-fold increase
(P<0.05) in template bleeding time. In contrast, UH had no significant effect on
CFRs at a dose (100 U/kg + 10 U/kg per minute) that resulted in anti-Xa levels of
1.2 to 1.6 IU/mL, anti-IIa levels of 1.8 to 2.4 IU/mL, an increase in APTT
greater than 10-fold over baseline, and a 2.5-fold increase (P<0.05) in template
bleeding time. Compared with the vehicle group, circulating platelet count and
hematocrit were not changed significantly by any dose of enoxaparin or UH tested.
Enoxaparin, unlike UH, prevented repetitive platelet-dependent thrombus formation
in the dog, thereby supporting the potential use of enoxaparin as a replacement
for heparin in the treatment of arterial thrombotic disorders such as unstable
angina.
PMID- 9633931
TI - Role of polymorphonuclear leukocytes in collar-induced intimal thickening in the
rabbit carotid artery.
AB - In this study, the involvement of polymorphonuclear leukocytes (PMNs) in the
development of intimal thickening was investigated. A fibromuscular intima was
induced by placing a silicone collar around the rabbit carotid artery for 3 days
or 2 weeks; the contralateral artery was sham operated. Rabbits received placebo
treatments (groups 1 and 3), granulocyte-colony stimulating factor (group 2; G
CSF, 20 microg x kg(-1) x d(-1), delivered by subcutaneous osmotic pumps), or an
anti-CD18 monoclonal antibody (group 4; 1.5 mg/kg i.v.). The G-CSF treatment
raised the peripheral PMN count 5- to 12-fold but had no effect on intimal
thickening on day 3, 12, or 14. A single injection of anti-CD18 prevented PMN
extravasation 6 hours after collar implantation without influencing intimal
hyperplasia on day 14. Repeated daily administration of anti-CD18 strongly bound
to CD18 on peripheral PMNs and inhibited both PMN-dependent plasma extravasation
in the skin and accumulation of CD14-immunoreactive leukocytes in the intima and
media. However, anti-CD18 did not suppress early intimal thickening or
accumulation of alpha-smooth muscle actin-immunoreactive cells by day 3. It thus
appears that the PMN influx in the intima and media evoked by the perivascular
collar is of little functional relevance to the subsequent smooth muscle cell
migration and intimal thickening in this model.
PMID- 9633932
TI - Intraluminal pressure is essential for the maintenance of smooth muscle caldesmon
and filamin content in aortic organ culture.
AB - Different forms of mechanical stimulation are among the physiological factors
constantly acting on the vessel wall. We previously demonstrated that subjecting
vascular smooth muscle cells (VSMCs) in culture to cyclic stretch increased the
expression of high-molecular-weight caldesmon, a marker protein of a
differentiated, contractile, VSMC phenotype. In the present work the effects of
mechanical factors, in the form of circumferential stress and shear stress, on
the characteristics of SM contractile phenotype were studied in an organ culture
of rabbit aorta. Application of an intralumininal pressure of 80 mm Hg to aortic
segments cultured in Dulbecco's modified Eagle's medium containing 20% fetal calf
serum for 3 days prevented the decrease in high-molecular-weight caldesmon
content (70+/-4% of initial level in nonpressurized vessel, 116+/-17% at 80 mm
Hg) and filamin content (80+/-5% in nonpressurized vessel, 100+/-2% at 80 mm Hg).
SM myosin and low-molecular-weight caldesmon contents showed no dependence on
vessel pressurization. Neither endothelial denudation nor alteration of
intraluminal flow rates affected marker protein content in 3-day vessel culture,
thus excluding the possibility of any shear or endothelial effects. Maintenance
of high high-molecular-weight caldesmon and filamin levels in the organ cultures
of pressurized and stretched vessels demonstrates the positive role of mechanical
factors in the control of the VSMC differentiated phenotype.
PMID- 9633933
TI - Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.
AB - In humans, production of the adipocyte-derived peptide leptin has been linked to
adiposity, insulin, and insulin sensitivity. We therefore considered that
alterations in plasma leptin concentrations could constitute an additional
component of a metabolic syndrome of cardiovascular risk. To explore this
hypothesis, we employed factor analysis, a multivariate statistical technique
that allows reduction of large numbers of highly intercorrelated variables to
composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3
years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of
coronary heart disease and diabetes underwent anthropometric measurements
(subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness
ratios, measurement of fasting plasma leptin, and an intravenous glucose
tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin
concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003),
S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24,
P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35,
P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and
IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between
leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations
emerged between plasma leptin concentrations and age, high density lipoprotein
cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI
(standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23,
P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors
of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI,
only IVGTT insulin emerged as a significant predictor of plasma leptin
concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma
leptin concentrations and the variables that are considered relevant to the
insulin resistance syndrome revealed a clustering of plasma leptin concentrations
with a factor dominated by insulin resistance and high IVGTT insulin, separate
from a high IVGTT glucose/central obesity factor and a high triglyceride/low high
density lipoprotein cholesterol factor. Together, these factors accounted for
55.9% of the total variance in the dataset. In conclusion, interindividual
variations in plasma leptin concentrations are strongly related to the principal
components of the insulin resistance syndrome. Further studies are needed to
determine whether the insulin-leptin axis plays a coordinating role in this
syndrome and whether plasma leptin concentrations could provide an additional
measure of cardiovascular risk.
PMID- 9633934
TI - IL-1beta-induced monocyte chemoattractant protein-1 gene expression in
endothelial cells is blocked by proteasome inhibitors.
AB - Human monocyte chemoattractant protein-1 (MCP-1) is expressed by a variety of
cell types in response to various stimuli. MCP-1 expressed by the endothelium
plays an important role in cell migration and activation. MCP-1 is a major
chemoattractant for monocytes, T lymphocytes, and basophils. In the present
study, we present evidence that the proteasome complex is involved in mediating
the interleukin (IL)-1beta induction of MCP-1 in endothelial cells. We present
evidence that a proteasome inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal
(norLeu), and the protease inhibitor tosyl-Phe-chloromethylketone (TPCK) block IL
1beta induction of MCP-1 protein expression. norLeu and TPCK also blocked IL
1beta-induced MCP-1 promoter-driven reporter gene expression as well as nuclear
factor (NF)-kappaB-mediated reporter gene expression. The effects of norLeu were
due to its inhibition of the proteasome rather than calpain, because other
calpain inhibitors had no effect on MCP-1 expression. In contrast to TPCK, which
blocked NF-kappaB translocation to the nucleus, norLeu had no effect on NF-kappaB
nuclear translocation or IL-1beta-induced phosphorylation of p65. This study
demonstrates that the proteasome pathway is involved in IL-1beta-induced MCP-1
gene expression in human endothelial cells.
PMID- 9633935
TI - Clinical features associated with the homozygous Trp64Arg mutation of the beta3
adrenergic receptor: no evidence for its association with obesity in Japanese.
AB - To characterize the clinical features associated with the Trp64Arg mutation of
the beta3-adrenergic receptor (beta3-AR), the effects of this mutation, in
particular the homozygous state (Arg/Arg), on obesity, blood pressure, and plasma
lipoproteins were investigated in 2 populations: subjects residing on a small
isolated island (group 1; n=746) and patients residing in Tokyo who attend a
clinic for metabolic diseases (group 2; n=371). The allelic frequency of the
Trp64Arg mutation was 23.4% in group 1 and 18.3% in group 2. No significant
difference in the body mass index was observed between subjects with 3 different
genotypes in each group. There was a trend that the Arg/Arg had higher systolic
blood pressure than the Trp/Trp in both groups, but the differences were not
statistically significant. The plasma LDL cholesterol levels were significantly
lower in Arg/Arg than in Trp/Trp in men from the group 1 cohort (2.82+/-0.84
versus 3.19+/-0.7 mmol/L, P<0.05). These results suggest that the homozygous
Trp64Arg mutation is not a major contributing factor for obesity, but potentially
contributed to higher systolic blood pressure and low plasma levels of LDL
cholesterol in Japanese men.
PMID- 9633936
TI - Interaction of diabetes and hypertension on determinants of endothelial
adhesiveness.
AB - Epidemiological studies have established that diabetes mellitus and hypertension
are independent risk factors for atherosclerosis. One of the earliest
abnormalities seen in atherogenesis is enhanced monocyte adherence to the
endothelium. The mechanisms by which diabetes mellitus or hypertension enhances
monocyte-endothelial cell interactions are incompletely characterized. It is not
known whether there are additive interactions between these risk factors on
endothelial adhesiveness for monocytes. Male Wistar-Kyoto (WKY) and spontaneously
hypertensive (SHR) rats were fed a normal or fructose-enriched diet. In some
cases, animals were injected with streptozotocin (35 mg/kg body weight) to induce
diabetes. After 2 weeks, plasma was drawn for biochemical measurements, and
thoracic aortas were harvested, opened longitudinally, and exposed to
fluorescently labeled mouse monocytoid cells (WEHI 78/24, 2 x 10(6)/mL) for 30
minutes on a rocking platform. Adherent cells were counted by epifluorescence
microscopy. WEHI 78/24 binding to aortic segments from SHR animals was elevated
compared with segments from WKYs. Fructose feeding alone had no effect on
endothelial adhesiveness. When WKYs were made hyperglycemic by STZ injection,
monocyte binding was 160% of the control value. Elevated monocyte binding was
also observed in aortas derived from SHR animals injected with STZ, indicating an
additive effect of hypertension and hyperglycemia. To determine whether
alterations in oxidative state played a role in the endothelial adhesiveness,
aortic segments were exposed to lucigenin (250 micromol/L) for measurement of
superoxide anion. Aortic segments from SHR elaborated 120% more superoxide anion
than did controls. Elevated free-radical production was also observed in aortas
from diabetic WKYs. Furthermore, thoracic aortas derived from diabetic SHR
animals elaborated more superoxide anion than did any of the other groups (374%,
P<0.05). Immunohistochemical staining for monocyte chemotactic protein-1
demonstrated increased expression in aortas isolated from diabetic WKY and SHR
compared with control vessels. These studies demonstrate that both diabetes and
hypertension lead to increased monocyte adherence to the endothelium. This
abnormality is associated with increased vascular superoxide production and
monocyte chemotactic protein-1 expression. Furthermore, there appears to be an
additive interaction between hyperglycemia and hypertension in their effects on
endothelial adhesiveness and its determinants.
PMID- 9633937
TI - In vivo efficacy of SM-20302, a GP IIb/IIIa receptor antagonist, correlates with
ex vivo platelet inhibition in heparinized blood but not in citrated blood.
AB - We tested the hypothesis that the in vivo antithrombotic efficacy of SM-20302, a
GP IIb/IIIa receptor antagonist, correlates with the ex vivo platelet inhibition
in heparinized platelet rich plasma (hPRP) but not in citrated PRP (cPRP). The
studies were performed in a canine model of carotid artery thrombosis in which
thrombus formation was induced by electrolytic injury. Thrombosis of the right
carotid artery was induced immediately after the administration of saline (n=12).
Thirty minutes after persistent occlusive thrombosis was obtained, the vessel
segment was ligated, and the time to occlusion and thrombus weight were noted.
Subsequently, thrombosis of the left carotid artery was initiated in the presence
of SM-20302 (100, 300, 600, or 1000 microg/kg i.v.; n=4 to 6). All the doses of
SM-20302 inhibited (by > or = 90%) the ex vivo platelet aggregation induced by
ADP and arachidonic acid (AA) in cPRP. In hPRP, a dose-dependent inhibition of ex
vivo platelet aggregation was observed. The maximal inhibition produced by 100 to
1000 microg/kg SM-20302 ranged from 18% to 80% for ADP and 44% to 88% for AA.
Maximal prolongation of the template bleeding time induced by the 100-, 300-, 600
, and 1000-microg/kg doses were 2.5-, 9.5-, 10-, and > 10-fold, respectively. All
the injured carotid arteries (n=12) in the saline-treated group occluded. SM
20302 pretreatment produced a dose-dependent maintenance of the carotid artery
patency, and the incidence of occlusion at 4 hours was 5/6, 3/6, 0/6, and 0/6 for
the 100-, 300-, 600-, and 1000-microg/kg doses, respectively. The results
indicate that SM-20302 prevents carotid artery thrombosis in response to
electrolytic arterial wall injury and that its in vivo antithrombotic efficacy
can be correlated accurately with the ex vivo platelet inhibition in PRP prepared
from heparinized blood but not from citrated blood.
PMID- 9633938
TI - Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is
mediated by an increase in NO synthesis.
AB - The low prevalence of coronary heart disease in premenopausal women and its
increase after menopause are well established. Although estrogen is thought to
play a role in protecting the vasculature, the mechanism has not been fully
clarified. The contribution of platelets to atherosclerotic cardiovascular
diseases is well recognized. The present study focused on the still-controversial
effect of estrogen on platelet function. We investigated the in vitro effects of
estrogen on human platelets, including their aggregation, Ca2+ metabolism, the
synthesis of cyclic nucleotides, and NO (nitrite/nitrate) synthesis after
stimulation with thrombin or ADP. Pretreatment of platelets with 17beta-estradiol
reduced the platelet aggregation induced by thrombin or ADP, whereas 17alpha
estradiol had no effect. 17Beta-estradiol accelerated the recovery of [Ca2+]i
after the agonist-induced peak and reduced the area under the curve of
accumulated platelet [Ca2+]i but did not alter the baseline [Ca2+]i, Ca2+ influx
induced by thrombin or ADP, the release of Ca2+ from internal stores, or the size
of internal Ca2+ stores. Pretreatment of platelets with 17beta-estradiol had no
effect on the intracellular concentration of cAMP but increased that of cGMP in
agonist-stimulated platelets. Additionally, 17beta-estradiol increased the
platelet concentration of nitrite/nitrate in a dose-dependent manner. These
effects of 17beta-estradiol on platelet aggregation, Ca2+ metabolism, and NO
synthesis were abolished by exposure to N(G)-monomethyl-L-arginine, an NO
synthesis inhibitor. These results suggest that 17beta-estradiol plays an
important role in inhibiting platelet aggregation by promoting Ca2+ extrusion or
reuptake activity that is dependent on the production of cGMP by increasing NO
synthesis.
PMID- 9633939
TI - Apolipoprotein B-48 or its apolipoprotein B-100 equivalent mediates the binding
of triglyceride-rich lipoproteins to their unique human monocyte-macrophage
receptor.
AB - Studies in animals and humans have demonstrated uptake of plasma chylomicrons
(triglyceride-rich lipoprotein [TGRLP] of Sf>400) by accessible macrophages in
vivo. One potential mechanism is via a unique receptor pathway we previously
identified in human blood and THP-1 monocytes and macrophages for the lipoprotein
lipase (LpL)- and apolipoprotein (apo) E-independent, high-affinity, specific
binding of plasma chylomicrons and hypertriglyceridemic VLDL (HTG-VLDL) to cell
surface membrane-binding proteins (MBP 200, 235; apparent Mr 200, 235 kD on SDS
PAGE) that leads to lipid accumulation in vitro. Competitive binding studies
reported here demonstrate that anti-apoB antibodies specifically block the high
affinity binding of TGRLP to this receptor on THP-1 cells and on ligand blots.
LpL, which binds to an N-terminal domain of apoB, also inhibits TGRLP binding
both to this site on THP-1s and to MBP 200, 235 by binding to apoB. Chylomicrons
of Sf>1100 that contain apoB-48, but not apoB-100, bind specifically to MBP 200,
235, and this binding is blocked by anti-apoB IgG. In contrast, lactoferrin and
heparin do not inhibit TGRLP binding. We conclude that the receptor-binding
domain is within apoB-48 (or an equivalent in apoB-100) near the LpL-binding
domain, but not a heparin-binding domain. Uptake of TGRLP by this mechanism could
provide essential nutrients or, in HTG, cause excess lipid accumulation and foam
cell formation.
PMID- 9633940
TI - Oxidized cholesterol in the diet accelerates the development of aortic
atherosclerosis in cholesterol-fed rabbits.
AB - Oxidized lipoproteins may play a role in atherosclerosis. Recently, we have
demonstrated that the levels of oxidized fatty acids in the circulation correlate
directly with the quantity of oxidized fatty acids in the diet and that dietary
oxidized fatty acids accelerate atherosclerosis in rabbits. The present study
tests the hypothesis that oxidized cholesterol in the diet accelerates the
development of atherosclerosis. Rabbits were fed a diet containing 0.33%
nonoxidized cholesterol (control diet) or the same diet containing 0.33%
cholesterol of which 5% was oxidized (oxidized diet). Serum cholesterol levels
increased to a similar extent in both groups, with the majority of cholesterol in
the beta-VLDL fraction. Moreover, in the serum beta-VLDL fraction and liver,
there was a significant increase in the oxidized cholesterol levels. Most
importantly, feeding a diet enriched in oxidized cholesterol resulted in a 100%
increase in fatty streak lesions in the aorta. Western diets contain high
concentrations of oxidized cholesterol products, and our results suggest that
these foods may be a risk factor for atherosclerosis.
PMID- 9633941
TI - Dominant negative effect of TGF-beta1 and TNF-alpha on basal and IL-6-induced
lipoprotein(a) and apolipoprotein(a) mRNA expression in primary monkey hepatocyte
cultures.
AB - Lipoprotein(a) [Lp(a)] consists of apolipoprotein(a) [apo(a)] disulfide linked to
apolipoprotein B-100 of LDL. Elevated plasma Lp(a) is an independent risk factor
for a variety of vascular diseases. Lp(a) has been reported to be an acute-phase
reactant, suggesting that cytokines may regulate its levels. To determine whether
Lp(a) expression was subject to modulation by cytokines, primary monkey
hepatocytes that endogenously express Lp(a) were used. Hepatocytes were treated
with interleukin (IL)-6, the major mediator of the acute-phase response, and
several other cytokines. IL-6 treatment (0.3 to 10 ng/mL) resulted in a marked,
dose-dependent, 2- to 4-fold enhancement of Lp(a) accumulation in the hepatocyte
culture media that was highly correlated with changes in apo(a) mRNA levels
(r>0.9). Several other cytokines, such as IL-2, IL-8, and hepatocyte growth
factor, had no significant effect on Lp(a) levels; however, transforming growth
factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) were very
active in inhibiting Lp(a) accumulation in the culture media, with IC50s of
approximately 0.3 and 1 ng/mL, respectively. Both TGF-beta1 and TNF-alpha also
decreased the apo(a) transcript. Mixing experiments, in which hepatocytes were
treated with 10 ng/mL of IL-6 and 0.3 to 10 ng/mL of TGF-beta1 or TNF-alpha,
demonstrated that the IL-6-mediated induction of Lp(a) and apo(a) mRNA was
ablated with very low levels of either inhibitory cytokine, suggesting a dominant
negative effect of TGF-beta1 and TNF-alpha. These results show that Lp(a) and
apo(a) mRNA expression in primary monkey hepatocytes is subject to both positive
(IL-6) and negative (TGF-beta1 and TNF-alpha) regulation by physiological levels
of cytokines. Thus, in vivo Lp(a) levels may be dependent on the balance between
stimulatory and inhibitory cytokines.
PMID- 9633942
TI - Hormone-sensitive lipase overexpression increases cholesteryl ester hydrolysis in
macrophage foam cells.
AB - Atherosclerosis is a complex physiopathologic process initiated by the formation
of cholesterol-rich lesions in the arterial wall. Macrophages play a crucial role
in this process because they accumulate large amounts of cholesterol esters (CEs)
to form the foam cells that initiate the formation of the lesion and participate
actively in the development of the lesion. Therefore, prevention or reversal of
CE accumulation in macrophage foam cells could result in protection from multiple
pathological effects. In this report, we show that the CE hydrolysis catalyzed by
neutral cholesterol ester hydrolase (nCEH) can be modulated by overexpression of
hormone-sensitive lipase (HSL) in macrophage foam cells. For these studies, RAW
264.7 cells, a murine macrophage cell line, were found to be a suitable model of
foam cell formation. HSL expression and nCEH activity in these cells and in
peritoneal macrophages were comparable. In addition, antibody titration showed
that essentially all nCEH activity in murine macrophages was accounted for by
HSL. To examine the effect of HSL overexpression on foam cell formation, RAW
264.7 cells were stably transfected with a rat HSL cDNA. The resulting HSL
overexpression increased hydrolysis of cellular CEs 2- to 3-fold in lipid-laden
cells in the presence of an acyl coenzyme A:cholesterol acyltransferase (ACAT)
inhibitor. Furthermore, addition of cAMP produced a 5-fold higher rate of CE
hydrolysis in cholesterol-laden, HSL-overexpressing cells than in control cells
and resulted in nearly complete hydrolysis of cellular CEs in only 9 hours,
compared with <50% hydrolysis in control cells. Thus, HSL overexpression
stimulated the net hydrolysis of CEs, leading to faster hydrolysis of lipid
deposits in model foam cells. These data suggest that HSL overexpression in
macrophages, alone or in combination with ACAT inhibitors, may constitute a
useful therapeutic approach for impeding CE accumulation in macrophages in vivo.
PMID- 9633943
TI - Estradiol stimulates apolipoprotein A-I- but not A-II-containing particle
synthesis and secretion by stimulating mRNA transcription rate in Hep G2 cells.
AB - Estrogen therapy increases plasma HDL levels, which may reduce cardiovascular
risk in postmenopausal women. The mechanism of action of estrogen in influencing
various steps in hepatic HDL and apolipoprotein (apo) A-I synthesis and secretion
are not fully understood. In this study, we have used the human hepatoblastoma
cell line (Hep G2) as an in vitro model system to delineate the effect of
estradiol on multiple regulatory steps involved in hepatic HDL metabolism.
Incubation of Hep G2 cells with estradiol resulted in the following statistically
significant findings: (1) increased accumulation of apoA-I in the medium without
affecting uptake/removal of radiolabeled HDL-protein; (2) accelerated
incorporation of [3H]leucine into apoA-I; (3) selective increase in [3H]leucine
incorporation into lipoprotein (LP) A-I but not LP A-I+A-II HDL particles (HDL
particles without and with apoA-II, respectively); (4) increased ability of apoA
I-containing particles to efflux cholesterol from fibroblasts; (5) stimulated
steady state apoA-I but not apoA-II mRNA expression; and (6) increased newly
transcribed apoA-I mRNA message without effect on apoA-I mRNA half-life. The data
indicate that estradiol stimulates newly transcribed hepatic apoA-I mRNA,
resulting in a selective increase in LP A-I, a subfraction of HDL that is
associated with decreased atherosclerotic cardiovascular disease, especially in
premenopausal women.
PMID- 9633944
TI - Association of specific LDL receptor gene mutations with differential plasma
lipoprotein response to simvastatin in young French Canadians with heterozygous
familial hypercholesterolemia.
AB - In familial hypercholesterolemia (FH), the efficacy of the inhibitors of 3
hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase shows considerable
interindividual variation, and several genetic and environmental factors can
contribute to explaining this variability. A randomized, double-blind, placebo
controlled clinical trial with simvastatin, an HMG-CoA reductase inhibitor, was
conducted in 63 children and adolescents with heterozygous FH. The patients were
grouped according to known LDL receptor genotype. After 6 weeks of treatment with
20 mg/d simvastatin, the mean reduction in plasma LDL cholesterol in patients
with the W66G mutation (n=14) was 31%, whereas in the deletion>15 kb (n=23) and
the C646Y mutation groups (n=10), it was 38% and 42%, respectively (P<0.05).
After treatment with simvastatin, HDL cholesterol levels were increased in all
groups, and triglyceride concentrations were significantly reduced. Multiple
regression analyses suggested that 42% of the variation of the LDL cholesterol
response to simvastatin can be attributed to variation in the mutant LDL receptor
locus, apolipoprotein E genotype, and body mass index, while 35% of the variation
in HDL cholesterol response was explained by sex and baseline HDL cholesterol.
These results show that simvastatin was an effective and well-tolerated therapy
for FH in the pediatric population for all LDL receptor gene mutations. Moreover,
the nature of LDL receptor gene mutations and other genetic and constitutional
factors play a significant role in predicting the efficacy of simvastatin in the
treatment of FH in children and adolescents.
PMID- 9633945
TI - Low expression of the apolipoprotein B mRNA-editing transgene in mice reduces LDL
levels but does not cause liver dysplasia or tumors.
AB - Hepatic expression of apolipoprotein (apo) B mRNA-editing enzyme catalytic
polypeptide 1 (APOBEC-1) has been proposed as a gene therapy approach for
lowering plasma low density lipoprotein (LDL) levels. However, high-level
expression of APOBEC-1 in transgenic mouse and rabbit livers causes liver
dysplasia and hepatocellular carcinoma. To determine the physiological and
pathological effects of low-level hepatic expression of APOBEC-1, we used a 52-kb
rat APOBEC-1 genomic clone (RE4) to generate transgenic mice expressing low
levels of APOBEC-1 (2 to 5 times those in nontransgenic mice). Liver function,
liver histology, editing of apoB mRNA at the normal editing site (C6666), and
abnormal editing at multiple sites (hyperediting) in these mice were compared
with those in transgenic mice expressing intermediate (I-20) or high (I-28)
levels of APOBEC-1 in the liver. Hyperediting of mRNA coding for the novel APOBEC
1 target 1 (NAT1) was also examined. In the high-expressing I-28 line, 50% of the
mice had palpable tumors at 15 weeks of age, whereas in the intermediate
expressing I-20 line, 50% of the mice had evidence of liver tumors after 1 year.
In contrast, low-expressing RE4 mice had normal liver function and histology and
did not develop liver tumors when examined at 3 to 17 months of age. Moreover,
hyperediting of apoB and NAT1 mRNA in the liver was robust in the I-20 mice but
barely detectable in the RE4 mice. The low-level expression resulted in
sufficient APOBEC-1 to edit essentially all apoB mRNA at the normal editing site,
virtually eliminating apoB-100 and LDL in the plasma of RE4 mice. When RE4 mice
were crossed with human apoB transgenic mice, which possess high plasma LDL
concentrations, plasma LDL levels in the offspring were reduced to very low
levels. These results indicates that long-term hepatic expression of APOBEC-1 at
low levels sufficient to eliminate LDL does not cause apparent liver damage or
liver tumors in transgenic mice. RE4 APOBEC-1 transgenic mice should prove
valuable for studying the roles of apoB-containing lipoproteins in lipid
metabolism and atherosclerosis.
PMID- 9633946
TI - Applications of the FIB lift-out technique for TEM specimen preparation.
AB - A site-specific technique for cross-section transmission electron microscopy
specimen preparation of difficult materials is presented. A focused ion beam was
used to slice an electron transparent membrane from a specific area of interest
within a bulk sample. Micromanipulation lift-out procedures were then used to
transport the electron-transparent specimen to a carbon-coated copper grid for
subsequent TEM analysis. The FIB (focused ion beam) lift-out technique is a fast
method for the preparation of site-specific TEM specimens. The versatility of
this technique is demonstrated by presenting cross-sectioned TEM specimens from
several types of materials systems, including a multi-layered integrated circuit
on a Si substrate, a galvanized steel, a polycrystalline SiC ceramic fiber, and a
ZnSe optical ceramic. These specimens have both complex surface geometry and
interfaces with complex chemistry. FIB milling was performed sequentially through
different layers of cross-sectioned materials so that preferential sputtering was
not a factor in preparing TEM specimens. The FIB lift-out method for TEM analysis
is a useful technique for the study of complex materials systems for TEM
analysis.
PMID- 9633947
TI - Superior preservation of the staphylococcal glycocalyx with aldehyde-ruthenium
red and select lysine salts using extended fixation times.
AB - The utility of lysine-based aldehyde-ruthenium red fixatives for the preservation
and/or staining of the fibrous staphylococcal glycocalyx was improved by
substitution of alternative forms of lysine for the free amino form.
Paraformaldehyde-glutaraldehyde fixatives containing alternative lysines, with or
without ruthenium red, were compared at short 20-minute prefixation times and at
extended overnight fixation times. Although inclusion of paraformaldehyde made
longer fixation times possible, the length of time for "safe" fixation varied per
sample and could not be predicted. All alternative lysine forms permitted
fixation of at least 24 hours without sample loss. The L-lysine monohydrochloride
or L-lysine acetate forms permitted longer fixation times than the L-lysine free
amino form, and they had comparable or better preservation of the staphylococcal
glycocalyx. Thus, the usefulness of aldehyde-lysine-based fixatives with minor
changes has been enhanced.
PMID- 9633948
TI - Lack of topography in the ventral nucleus of the lateral lemniscus.
AB - In contrast to the ease of finding tonotopicity in other nuclei, both anatomical
and electrophysiological methods have failed to demonstrate a clear and simple
tonotopic map within the ventral nucleus of the lateral lemniscus (VLL). The
present study was undertaken in cat with the hope that methods not used
previously in studies of VLL might succeed in demonstrating an orderliness in its
exiting fibers (i.e., efferents) or its incoming fibers (i.e., afferents). Since
the same organization of ascending frequencies present in the cochlea is
maintained in these fibers as well as in all main auditory nuclei, demonstration
of a similar organization of frequencies in VLL would be evidence of the cochleo-
or tono-topicity of this nucleus. Using triple injection of 3 different
fluorescent dyes in inferior colliculus to study efferents, orderly and tonotopic
cell-labeling is found in each of the brainstem auditory nuclei, with the notable
exception of VLL. Instead, labeling of cell clusters, each cluster containing a
small number of cells, is found randomly distributed throughout VLL in all 3 of
its spatial dimensions. Using the 2-deoxyglucose (2-DG) method, during
stimulation at 6 different frequencies, afferent orderliness, indeed,
tonotopicity is found in all major brainstem auditory nuclei, again with the
notable exception of VLL. Rather, each frequency evokes 2-DG label throughout
VLL. In agreement with the results based on electrophysiological methods,
therefore, the anatomical methods used here also yield no evidence of
tonotopicity in VLL. Thus, if there is orderliness in VLL's efferents or
afferents, it is based on an auditory dimension incommensurate with frequency.
PMID- 9633949
TI - Morphological examination of bone synthesis via direct administration of basic
fibroblast growth factor into rat bone marrow.
AB - Woven bone induced by direct injection of basic fibroblast growth factor (bFGF)
into rat bone marrow was examined. On the first day after injection, fibrous
tissues formed in the treated region of the bone marrow. Tissue-nonspecific
alkaline phosphatase (TNAPase)-immunopositive osteoblastic cells and osteopontin
immunopositive-extracellular matrices were observed in the fibrous tissues,
indicating bone induction. On the fifth day, the bFGF-induced bone was found
broadly in the bone marrow. In the originally existing bone, osteopontin
immunoreactivity was observed at cement lines, but not in the fully calcified
matrix, whereas the woven bone displayed immunoreactivity throughout the matrix.
Numerous TRAPase-positive osteoclasts were present on the surfaces of the woven
bone, but no obvious cement line was observed. Therefore, both bone formation and
resorption appeared highly active, without normal cellular coupling equilibrated
between bone formation and resorption performed by osteoblasts and osteoclasts.
On the tenth day, the bFGF-induced bone was almost replaced by bone marrow. Thus,
bone formation actively occurred in the first half of the experimental period,
whereas bone resorption came to be predominant thereafter. This study
demonstrated that bFGF stimulates bone formation, which, however, is subject to
subsequent resorption, probably due in part to the absence of coordinated
cellular coupling between osteoclasts and osteoblasts.
PMID- 9633950
TI - Photochemically induced focal cochlear lesions in the guinea pig: I. DAB staining
and SEM study.
AB - A photochemical reaction was used to produce focal microcirculation disorders in
the guinea pig cochlea. Temporal bones were removed at various intervals between
5 minutes and 1 month after infusion of rose bengal (RB) and illumination.
Infused but unilluminated contralateral cochleae served as controls. Dissected
cochlear structures were stained by 3,3'-diaminobenzidine (DAB) peroxidase
substrate medium. After observation by light microscopy (LM), the same specimens
were processed and observed by scanning electron microscopy (SEM). Dilation of
strial capillaries and destruction of strial epithelial cells became apparent at
1 hour after illumination. Tightly packed red blood cells were found filling the
severed end of markedly dilated strial capillaries at 24 hours after the
procedure. DAB staining of the osseous spiral lamina indicated vascular change
with vessel dilation in the illuminated area. At 1 week after illumination, the
lesion area of the stria vascularis and spiral prominence was replaced by a layer
of larger, flat cells. At 1 month after illumination, all vascular supply to the
cochlear lateral wall disappeared at the site of illumination. All lesions
remained focal and showed no sign of expansion or reduction throughout the
observation period. The cochlear duct of the guinea pig appears to be segmentally
nourished by the capillary system. Observation of DAB stained tissue by LM and
SEM proved to be informative in the study of microcirculation disorders of the
inner ear.
PMID- 9633951
TI - Photochemically induced focal cochlear lesions in the guinea pig: II. A
transmission electron microscope study.
AB - Photochemically induced focal lesions in guinea pig cochleas were studied by
light microscopy and transmission electron microscopy. The lesions were induced
in the second cochlear turns of 35 adult guinea pigs by illumination for 10
minutes with a focused green light immediately after a rose bengal solution was
injected into the jugular vein. The cochlear lateral wall and organ of Corti were
examined 5, 10, 20, 30, and 90 minutes, 12 and 24 hours, and 3, 7, and 30 days
after the procedure. Aggregations of platelets and red blood cells were found in
strial capillaries at 5 minutes after illumination. After 30 minutes, marginal
cell surfaces protruded into the endolymphatic space; surface membranes were
ruptured and the cytoplasm was expelled into the space. In outer hair cells,
disruption of the cellular membrane was found near the cuticular plate 12 hours
after the procedure. All cellular elements of the lateral wall and organ of Corti
were markedly degenerated in the 30-day specimens. Histological changes found in
the stria vascularis were consistent with cell damage caused by active oxygen
species. It is likely that the stria vascularis is more sensitive to the
photochemical reaction than other parts of the cochlea. Cell damage in other
parts of the cochlea seemed to have been caused by local microvascular ischemia
in addition to the action of active oxygen species induced by the photochemical
reaction.
PMID- 9633952
TI - Biplane color flow duplex intravenous intravascular ultrasound for arterial
visualization.
AB - PURPOSE: To describe a feasibility study in a sheep model using an intravascular
ultrasound (IVUS) instrument in an intravenous position to produce color flow, B
mode images of arterial segments along with Doppler blood flow velocities.
METHODS: Four healthy adult male sheep were anesthetized for surgical exposure of
the right external jugular vein. A 9.0F sheath was also introduced in the common
femoral artery for arteriography and device insertion. A 7.5-MHz ultrasound probe
with 1-cm graduation markers was passed into the jugular vein. B-mode and color
flow pictures were captured at aortic branches in cross and longitudinal
sections. Length measurements between aortic branches and Doppler spectral
velocities were obtained. Guidewire, balloon, and stent maneuvers were monitored
by the stationary intravenous IVUS probe. RESULTS: High-quality visualization of
the entire abdominal aorta and its branches was achieved in all animals. With the
probe stationary in the vena cava, a 1.5-cm linear segment of the aorta could be
continuously observed in both B-mode and color flow ultrasound scans. Insertion
and implantation of a Palmaz balloon-expandable stent was guided by intravenous
IVUS alone. Selective catheterization of the right renal artery was followed
visually by moving the intravenous IVUS probe sequentially. CONCLUSIONS:
Intravenous IVUS appears feasible as a guidance and monitoring tool for
endovascular interventions. While conventional IVUS provides only cross-sectional
images in B-mode, intravenous IVUS captures color flow and Doppler velocity data
as well. These added ultrasound modalities may offer potential advantages for
guidance of endovascular procedures and endoleak detection.
PMID- 9633953
TI - Intravascular ultrasound in endovascular stent-grafts for peripheral aneurysm: a
clinical study.
AB - PURPOSE: To evaluate the potential diagnostic information of intraprocedural
intravascular ultrasound (IVUS) in patients undergoing endovascular stent
grafting for peripheral aneurysm. METHODS: IVUS was used in 17 patients
preprocedurally to measure the diameter of the proximal and distal neck and the
length of the aneurysm. Balloon and stent-graft sizes were selected based on
these measurements. Following stent-graft deployment, angiography and IVUS were
used to document stent apposition and the configuration and diameter of the stent
graft. RESULTS: Stent-graft insertion was considered successful in 8 patients
based on angiography and IVUS images. In 9 others, both imaging modalities showed
inadequate results, necessitating 12 additional procedures: balloon angioplasty
for stent-graft stenosis (2) and inadequate stent-graft apposition (1); an
additional stent-graft (4); an extra stent (1); thrombectomy (2); and conversion
(2) for inadequate stent-graft position and a graft rupture. In these patients,
intraprocedural IVUS was superiorto angiography in contributing vital information
to aid in the selection of the additional interventions. CONCLUSIONS: During
management of peripheral aneurysms with endovascular stent-grafts, IVUS
monitoring was a useful adjunct when the initial procedure was unsatisfactory
and/ or when intraprocedural angiographic studies were inconclusive.
PMID- 9633954
TI - Diameter of large balloons used in endoluminal graft deployment varies with
inflation pressure.
AB - PURPOSE: To evaluate the characteristics of large-diameter balloon catheters used
during endoluminal repair of aortic aneurysms. METHODS: Thirty-three large
balloon dilatation catheters in the diameter range of 15 to 30 mm were measured
at controlled pressures from 1 to 4 atm. The balloons were inflated with water
using an inflation syringe connected to a pressure transducer. Diameters at
stable pressure and pressure changes against time were recorded for each balloon.
RESULTS: Dilation catheters in the range of 15 to 20 mm in diameter were
significantly smaller (p < 0.005) than their nominal diameter at 1 and 2 atm;
they reached nominal diameter only at the relatively high pressure of 4 atm. Most
larger diameter balloons (25 and 30 mm) did not attain their nominal diameter
even with pressures up to 4 atm. All sizes of balloon catheters tested became
relatively compliant at pressures > 3 atm. CONCLUSIONS: The large balloon
catheters tested in this study were designed for arterial angioplasty or
valvuloplasty. They attained a significantly smaller size than their nominal
diameter at pressures < 3 atm and became compliant at pressures exceeding 3 atm.
Interventionists should be aware of these characteristics when using balloon
catheters such as these during endoluminal graft deployment. Large balloons that
reach predictable diameter at lower pressures should be designed specifically for
use in endoluminal graft procedures.
PMID- 9633955
TI - Treatment of traumatic false aneurysm of the thoracic aorta with endoluminal
grafts.
AB - PURPOSE: Traumatic false aneurysms of the thoracic aorta presenting at a time
remote from the original injury are a rare but complex problem. The treatment of
a traumatic false aneurysm by endovascular techniques may offer many advantages
over conventional open surgery. METHODS AND RESULTS: Two male patients presented
with traumatic false aneurysm of the thoracic aorta after being treated
emergently for visceral injuries from a gunshot wound in one and an automobile
accident in the other. In both cases, the aneurysm was situated so that only the
T11 intercostal artery would be sacrificed by endoluminal exclusion. Commercially
available endoluminal stent-grafts (Talent) were deployed successfully. Recovery
in both patients was rapid and uneventful with no neurological sequelae. Spiral
computed tomographic scans at 1 year indicated sustained aneurysm exclusion and
satisfactory endograft position. CONCLUSIONS: A customized endoluminal stent
graft can be used with great accuracy to exclude thoracic false aneurysms,
avoiding the potential complexity and morbidity of an open thoracic approach.
PMID- 9633956
TI - The effect of angulation on intravascular ultrasound imaging observed in vascular
phantoms.
AB - PURPOSE: To quantify the error introduced by noncoaxial intravascular ultrasound
(IVUS) imaging and to evaluate the use of a balloon-tipped catheter in
compensating for intraluminal angulation and subsequent dimensional inaccuracy.
METHODS: The effect of noncoaxial IVUS imaging was investigated in both a
polyvinyl chloride phantom and an in vitro canine aorta using a calibrated setup
to measure angulation off axis. Imaging was performed at increasing angulation
(creating an elliptical image) in both phantoms, with the transducer centered and
off center. Diameters were compared to the original coaxial diameter, as well as
calculated diameters based on specific angles off axis. The percentage change
(error) was also calculated at these angles. The measurements were repeated using
a balloon-tipped catheter to center the transducer. RESULTS: The measured
diameters and percentage changes compared closely with their calculated
counterpart. Up to 25 degrees off axis, the apparent increase in diameter
measurement was nearly 10%. Angulation from 30 degrees to 70 degrees resulted in
an increase of 15% to 192%. Use of the centering balloon reduced the amount of
error by 70% to 85% but was limited to angles < or = 25 degrees due to the design
of the test apparatus. CONCLUSIONS: The error introduced by noncoaxial IVUS
imaging can be significant and may be partially corrected by the use of a
centering balloon. Further studies in the clinical application of a centering
device are warranted.
PMID- 9633957
TI - Emergent endoluminal repair of delayed abdominal aortic rupture after blunt
trauma.
AB - PURPOSE: To report the emergency repair of a traumatic abdominal aortic rupture
using endoluminal techniques. METHODS AND RESULTS: A 25-year-old female sustained
multiple head, chest, and abdominal injuries in a motorcycle accident. Six days
after emergency treatment (including splenectomy and repair of a superficial
hepatic rupture and lacerations to the stomach, small bowel, and colon), she
became hemodynamically unstable. A massive retroperitoneal hematoma had evolved
from a distal aortic rupture. Owing to a hostile abdomen and possibility of
bacterial contamination, a self-expanding stent-graft was inserted transfemorally
to repair the aortic injury. The patient recovered uneventfully and continues in
good health with a patent endograft repair 2 years after treatment. CONCLUSIONS:
This experience would support the efficacy of endograft implantation for emergent
repair of trauma aortic injuries; however, proper facilities, an experienced
interventional team, and an assortment of endografts and stents must be
available.
PMID- 9633958
TI - Transluminal stent-graft repair for pseudoaneurysm of PTFE hemodialysis grafts.
AB - PURPOSE: To report the use of endovascular techniques to treat two cases of
nonanastomotic pseudoaneurysm of a bridge graft fistula (BGF). METHODS AND
RESULTS: Two men with fully functional polytetrafluoroethylene (PTFE) BGFs both
presented with an enlarging mass adjacent to their arteriovenous shunt. The false
aneurysm in both instances was located by ultrasound and confirmed by shunt
angiography at the time of surgery. Both fistulas were repaired by transluminally
introducing a stented graft composed of a balloon-expandable Palmaz stent covered
with a PTFE graft. Completion arteriography confirmed normal flow through the
graft with no communication between the lumen and the aneurysmal cavity. Both
patients recovered without complications and were discharged on the day of the
procedure. Follow-up data reveal that both fistulas remain fully functional up to
5 and 6 months, respectively. CONCLUSIONS: Endovascular repair using stent-grafts
can be a safe and effective method of excluding pseudoaneurysms associated with
PTFE BGFs.
PMID- 9633959
TI - Iliofemoral venous thrombosis caused by compression of an internal iliac artery
aneurysm: a minimally invasive treatment.
AB - PURPOSE: To report the success of a minimally invasive treatment for phlegmasia
cerulea dolens without gangrene caused by compression from an internal iliac
artery aneurysm. METHODS AND RESULTS: An 81-year-old male with a 1-month history
of paralysis owing to a hemorrhagic stroke presented with massive edema and skin
mottling of the right lower extremity. Imaging confirmed right iliofemoral deep
vein thrombosis caused by compression from a 4-cm internal iliac artery aneurysm.
With thrombolysis ruled out, a minimally invasive treatment plan was undertaken,
featuring percutaneous coil embolization of the aneurysm and surgical venous
thrombectomy with proximal arteriovenous fistula creation and iliac vein stent
placement. Failure of the coils to embolize the iliac aneurysm prompted the use
of an endovascular graft to exclude the aneurysm. The patient's symptoms
subsided, and he has a patent right iliofemoral venous system and internal iliac
artery at his latest (16-month) follow-up. CONCLUSIONS: This case demonstrates
that minimally invasive endovascular and open techniques can be combined to
achieve an optimum outcome in patients at high risk for standard surgical
approaches.
PMID- 9633960
TI - The vascular laboratory: a critical component required for successful management
of peripheral arterial occlusive disease.
PMID- 9633961
TI - Type I and Type II endoleaks: a more useful classification for reporting results
of endoluminal AAA repair.
PMID- 9633962
TI - Combined endovascular/laparoscopic approach to aortic pseudoaneurysm repair.
PMID- 9633963
TI - Understanding tracheomalacia.
AB - Tracheomalacia is an abnormality of the trachea that probably is present to some
degree in all infants and children with oesophageal atresia. It causes the
trachea to collapse during breathing, leading to obstruction of the upper airway.
Our knowledge of the structural abnormalities underlying tracheomalacia is
limited, mainly because patients with oesophageal atresia usually survive.
Recently, the Adriamycin-induced rat model of oesophageal atresia and
tracheomalacia has clarified some aspects of its pathology and the factors which
may influence its development. The rat model suggests that the same detrimental
factors that cause oesophageal atresia might also affect the development of the
trachea, and that anomalous great vessels may exacerbate the severity of
tracheomalacia locally.
PMID- 9633964
TI - Medical student education in paediatrics and child health: where are we going?
AB - In most undergraduate medical curricula, learning is becoming less content based
and the emphasis is changing to problem based learning, continuing self directed
learning, and the use of a wide range of learning resources. Particular needs in
paediatrics and child health are an increasing emphasis on learning in ambulatory
care and community based health facilities, and on assessment processes which are
formative and reflect the learning objectives appropriately. A wide range of
resources is needed for learning at a time when teaching hospital and health
system facilities face significant financial restraints.
PMID- 9633965
TI - Reducing the risk of sudden infant death syndrome: a review of the scientific
literature.
AB - In March 1997 a multidisciplinary forum was convened by the National SIDS Council
of Australia to review recent evidence concerning risk factors of sudden infant
death syndrome (SIDS) and to revise and refine the current guidelines for
reducing the risk of SIDS. The forum provided an assessment of the evidence for
recommendations to reduce the risk of SIDS using an evidence-based process.
Strong evidence has now accumulated that the intervention campaigns to reduce
prone sleeping during infancy have been followed by SIDS rate declines. Recent
data indicate that the supine position is not associated with an increase in
significant morbidity outcomes and provides greater protection for SIDS than the
side position, which may be unstable. Covering of the baby's head by bedding is
strongly related to SIDS. The infant's sleeping environment should be carefully
set up to ensure that the baby's head, including the face, cannot be obstructed
during sleep. Parental smoking is strongly associated with SIDS. Structural
supportive interventions for parental smoking cessation are required. Bedsharing
increases the risk of SIDS amongst smokers and the data are currently not
sufficient to provide complete reassurance to nonsmoking parents that bedsharing
is safe. Infants should be maintained in a comfortable temperature zone. The
evidence for a protective effect of breast-feeding is conflicting, so breast
feeding cannot be promoted strongly as reducing the risk of SIDS. Immunisation
has not been associated with SIDS. Parents and carers should be aware of the
current guidelines. Health professionals should also be aware of the evidence on
which the current recommendations are based. Effective health education
programmes should lead to a further decline in SIDS mortality in Australia.
PMID- 9633966
TI - Education for children with disabilities: the rationale for inclusion.
AB - OBJECTIVE: To discuss issues in the education of children with disabilities,
particularly with respect to inclusion in mainstream classes. METHODOLOGY: Review
of the literature on education for children with disabilities, focusing on the
inclusion versus segregation debate. RESULTS: The literature provides no support
for segregation and some support for the view that segregated children are
disadvantaged. What seems to be important is the way the child is educated rather
than where the education takes place. In addition, there are ethical,
sociological, and legal arguments in favour of an inclusive educational system.
CONCLUSIONS: There are good arguments to encourage inclusive education for
children with disabilities. In advising parents, doctors should focus on how
rather than where the child with a disability should be educated.
PMID- 9633967
TI - Urinary calcium excretion in Chinese adolescents.
AB - OBJECTIVES: To obtain normative reference values for urinary calcium excretion in
Chinese adolescents. METHODOLOGY: A random group of 425 healthy Chinese
adolescents aged 12-19 years were recruited from secondary schools in Hong Kong.
Each subject provided a sample of morning urine for the assessment of calcium and
creatinine excretion. A subgroup of 80 subjects provided a 24-h urine sample for
assessment of daily calcium excretion. RESULTS: The mean (+/-S.D.) and median
urinary calcium/creatinine concentration ratios (UCa/Cr) expressed in mmolmmol
creatinine were 0.18 (+/-0.16) and 0.12. Girls had a higher UCa/Cr than boys (P <
0.0001). The mean+/-S.D. 24-h urinary calcium excretion was 0.043+/-0.025 mmol kg
day(-1) (1.71+/-1.01 mg kg day(-1)). CONCLUSION: The UCa/Cr ratio and 24-h
urinary calcium excretion are low when compared with published values for
Caucasian children. The apparent rarity of nephrolithiasis and microscopic
haematuria associated with hypercalciuria may be related to the low urinary
calcium excretion in this population.
PMID- 9633968
TI - Humoral immune and clinical responses to food antigens following acute diarrhoea
in children.
AB - OBJECTIVE: To investigate the effect of acute watery diarrhoea in children upon
humoral immune responses to food antigens and the subsequent development of food
allergy. METHODOLOGY: Serum antibodies to cows' milk, beta-lactoglobulin, alpha
lactalbumin, bovine serum albumin and ovalbumin were measured in 30 children with
acute diarrhoea in the acute phase and 1 month after recovery. The children were
followed for 1 year to assess the development of food allergy. RESULTS: IgG
antibeta-lactoglobulin titres for the study group increased 1 month after
recovery compared to the titres during the acute phase (P = 0.02). Antibody
concentration for the other antigens studied did not rise. Four children
developed positive IgE antibodies to one or more of the allergens after the
diarrhoeal episode, although the titres were very low. None showed evidence of
allergy to cows' milk or egg during the year-long follow-up. CONCLUSIONS: Acute
diarrhoea in children resulted in increased production of IgG antibody to beta
lactoglobulin and had a priming effect for development of positive IgE antibody
to cows' milk. Clinical food allergy was not observed in any of the children
during the year-long follow-up.
PMID- 9633969
TI - Congenital malformations in Victoria, Australia, 1983-95: an overview of infant
characteristics.
AB - OBJECTIVE: To provide an overview of the characteristics of Victorian infants
born between 1983 and 1995 who are affected by one or more of 27 sentinel birth
defects. METHODOLOGY: Using data on congenital malformations supplied to the
Victorian Perinatal Data Collection Unit from multiple sources between 1983 and
1995, information was summarised for 25231 infants (born at 20 weeks or more) and
1566 terminations of pregnancy before 20 weeks' gestation. RESULTS: During the 13
year study period in Victoria, 3.2% of babies had at least one malformation.
Congenital dislocation of the hip was the most common defect with a prevalence of
28.9 per 10000 pregnancies or 1/346. Increase in birth prevalence between 1983
and 1995 is greatest in obstructive defects of the renal pelvis, hypospadias and
the trisomies 21,13 and 18. Nearly 50% of pregnancies affected by anencephaly
were terminated before 20 weeks compared to 26% affected by spina bifida. The
perinatal mortality of infants born at 20 weeks or more with congenital
malformations is more than 10 times greater than that of infants without any
malformations. Males are more at risk of being born with a malformation than
females. Congenital malformations are more common in infants of multiple
pregnancies and those of low birthweight. CONCLUSION: This large data collection
is a valuable source of information for perinatal epidemiologists, for providers
of prenatal diagnostic services and for the care of the disabled. In addition,
the continued reporting and monitoring of birth defects will allow for targeted
research that may lead to a better understanding of their aetiology.
PMID- 9633970
TI - Is a paediatrician needed at all Caesarean sections?
AB - OBJECTIVE: The need for a skilled neonatal resuscitator in the form of a
paediatrician or paediatric registrar to attend a vaginal delivery or Caesarean
section (CS) is not clearly defined. This study was undertaken in order to
ascertain the level of resuscitation a neonate might require dependent on the
delivery mode and type of anaesthesia used. METHODOLOGY: We analysed the
Tasmanian Obstetric Audit from 1980 to 1989 for the need for intubation and Apgar
scores at 1 min of term singleton deliveries by the mode of delivery. RESULTS:
The number of singleton term deliveries was 64739. When the data were analysed
annually there was a trend for a reduction in the need for intubation in CS
deliveries during the first 5 years, although this was not paralleled by an
improvement in Apgar scores. Thus the intubation rate data are also presented for
the last 5 years of the study. The intubation rate, Apgar score at 1 min of < 4,
and Apgar score at 1 min of > or = 4 < 7 for repeat CS under epidural anaesthesia
were 0.55% (0.26% for 1985-89) 0.83% and 3.58%, respectively, with relative risks
when compared with spontaneous normal vaginal delivery of 1.8 (1.2 for 1985-89),
0.7 and 0.5, respectively. The relative risk of these outcomes was higher than
for normal vaginal delivery for all other modes of delivery including repeat CS
under general anaesthesia. CONCLUSION: It is concluded that a paediatrician or
paediatric registrar is not required to routinely attend repeat CS under epidural
anaesthesia, but should be present for repeat CS under general anaesthesia.
PMID- 9633971
TI - Developmental-behavioural problems in general paediatrics.
AB - OBJECTIVE: To determine the current role of private general paediatrics in the
care of children with problems of development and behaviour. METHODS: We surveyed
all general paediatricians registered with the Australian College of Paediatrics
to assess their current role in developmental-behavioural (DB) problems--their
rate of referrals, their role in the continuing management, and opinions
regarding duration of training in this area. RESULTS: Of 394 questionnaires sent,
284 replies were received (72%). From these 284 we analysed results for all 172
who spent more than 25% of their time in private general paediatric practice. On
average, 32% of new referrals were for DB problems. With 10 DB clinical vignettes
presented, paediatricians chose to continue to manage in conjunction with allied
health services in 65% of cases. Other management choices included referral to a
multidisciplinary team (16%), referral elsewhere (10%) and manage alone (7%). For
training to be a general paediatrician, they indicated 3 months should be spent
during basic training in each of the three areas of; DB paediatrics,
developmental disabilities and child psychiatry (separately or concurrently); and
6 months of each during advanced training. Free comments highlighted lack of
public allied health and psychosocial services. CONCLUSION: Private community
based general paediatricians are deeply involved in this area of work. The
results raise questions about services for training and for clinical
collaboration between public and private child health providers.
PMID- 9633972
TI - Iron status and dietary iron intake of 6-24-month-old children in Adelaide.
AB - OBJECTIVE: Chronic iron deficiency in children is associated with anaemia and
impaired mental and psychomotor development. The aim of this study was to assess
the iron status and dietary intake of 6-24-month-old Caucasian and Asian children
living in metropolitan Adelaide. METHOD: A total of 234 healthy children (82%
Caucasian and 18% Asian) aged 6-24 months were studied. Dietary iron intake of
children was estimated from semiquantitative diet recall questionnaire
administered to their parents. Blood samples for full blood count, serum ferritin
(SF), serum iron (SI) and transferrin (TF) level estimations were obtained by
venesection. Based on the laboratory test results, infants were classified as
iron sufficient (IS) if the haemoglobin (Hb) concentration was > 110 g L(-1), SF
> or = 15 microg L(-1), TF2 3.0 g L(-1), SI > or = 8 micromol L(-1) and iron
saturation (ISAT) > or = 12%; or nonanaemic iron deficiency (NAID) if the Hb
concentration was > 110 g L(-1) and SF < 15 microg L(-1) or SI < 8 micromol L(
1), TF > 3.0 g L(-1), and ISAT < 12%; or as iron deficiency anaemia (IDA) if the
Hb concentration was < 110 g L(-1) in association with SF < 15 microg L(-1) or
with SI < 8 micromol L(-1), TF > 3.0 g L(-1) and ISAT < 12%. RESULTS: Sixty-nine
per cent of Caucasian children were classified IS, 25% as NAID and 6% were IDA;
while 72% of Asian children were classified IS, 14% as NAID and 14% were IDA.
Multivariate analysis demonstrated that factors associated with iron deficiency
(SF 5 microg L(-1)) included age, duration of breast-feeding and cows' milk
intake. CONCLUSION: Iron deficiency is common in our young population. Additional
strategies to prevent IDA need be developed and evaluated in Australian infants.
PMID- 9633973
TI - Children's understanding of sun protection behaviours: a comparative analysis.
AB - OBJECTIVE: To investigate awareness of sun protection behaviours in a sample of
primary school children in New Zealand. METHODOLOGY: Information was collected
from 824 primary school children in New Zealand using a drawing and writing
technique. RESULTS: The data revealed a bias towards sunscreen as a method of sun
protection compared with other methods such as clothing and the use of shade.
Comparisons between results obtained from children resident in Australia and
England indicated a greater awareness of sun protection methods amongst the
children from Australia and New Zealand compared with those children living in
England. CONCLUSIONS: Children as young as 5 and 6 can describe the consequences
of overexposure to the sun, and can illustrate methods of sun protection.
Sunscreen is seen as the main method of sun protection.
PMID- 9633974
TI - Sleep deprivation or postnatal depression in later infancy: separating the
chicken from the egg.
AB - OBJECTIVES: To explore the association between maternal distress and depression
in the first years of a newborn's life and the child's sleeping behaviour and
problems associated with this behaviour. To asses the effectiveness of an
outpatient-based individualised behaviour modification programme to modify
children's sleep behaviour and to decrease levels of maternal distress and
depression. METHOD: Families were referred to an outpatient childhood sleep
problems clinic. Intervention consisted of an individualised management programme
including recognised modes of child sleep behaviour management ('controlled
crying', 'cold turkey,' rewards) together with occasional use of short-term (less
than 2 weeks) tapering dose sedating medication for the child. Two months after
the initial contact with the clinic, families completed a second questionnaire
collating similar data to that collected at time of enrolment. RESULTS: A total
of 114 consecutive families referred to the clinic provided initial data. Follow
up questionnaires were returned by 70 (61%). Significant change was recorded in
children's sleep parameters including reduction in mean number of night time
awakenings (4.1-1.3, P < 0.001), proportion of children requiring longer than 30
min to settle at night (49% to 21%, P < 0.01) and in the proportion of children
settling after 8 pm (51% to 33%, P < 0.01). Sleep problem rating on a 0-10 scale
decreased from a mean of 8.1-3.1 (P < 0.001). On initial assessment, 40% of
mothers had Edinburgh Postnatal Depression Scale (EPNDS) scores greater than 12
(screening cut-off point). At repeat assessment, 4.3% had scores greater than 12.
The mean score on the EPNDS fell from 11.2 to 5.8 (P < 0.001). CONCLUSIONS: An
outpatient-based individualised approach to modifying children's problematic
sleep behaviour using recognised behaviour management techniques is effective.
Modification of problematic childhood sleep behaviour is associated with
significant improvement in maternal mood. Given the high incidence of childhood
sleep problem and diagnosed postnatal depression, it is likely significant
numbers of mothers being diagnosed as having postnatal depression are suffering
the effects of chronic sleep deprivation. Management of postnatal mood disorder
and childhood sleep behaviour must occur with due recognition to their close
association.
PMID- 9633975
TI - Childhood sleep problems: association with prenatal factors and maternal
distress/depression.
AB - OBJECTIVE: To determine whether problems with childhood sleep behaviour are
associated with either maternal sleep patterns and emotional status during the
pregnancy period, or levels of maternal distress and depression during the
postnatal period. METHODOLOGY: A case/control comparison study. Cases were
families presenting for admissions to a mother/baby hospital in Brisbane with the
major presenting problem being the child's sleep behaviour. The control group
consisted of families presenting for well child health care to one of four child
health centres in suburban Brisbane. Each participating mother provided
information by way of a self-report questionnaire on social and demographic
variables, children's sleep patterns, maternal emotional adjustment and maternal
sleep pattern during the pregnancy, and current problem with child's sleep
behaviour. Current level of maternal distress/depression, was measured using the
Edinburgh Postnatal Depression Scale. Cases were compared with controls on all
these variables. RESULTS: Significant differences were found between groups in
childhood sleep parameters, degree of problem related to childhood sleep,
maternal sleep variables during the entire pregnancy, and current levels of
maternal distress/depression. CONCLUSION: The origins of problematic childhood
sleep behaviour may lie in the pregnancy period. Levels of maternal distress and
depression are associated with problematic childhood sleep behaviour. The issue
of whether childhood sleep problem predisposes to maternal distress/depression
needs exploration. Assessment of maternal mood disorder or childhood sleep
problems should be comprehensive and involve both the maternal infant dyad and
the family network.
PMID- 9633976
TI - Paediatric assessment in a residential child and adolescent psychiatry unit.
AB - OBJECTIVE: To document the health status, comorbidity and functional impairments
experienced by a group of psychiatrically disturbed children and adolescents.
METHODOLOGY: A detailed study of consecutive admissions to a residential unit
over a two-year period was undertaken. All admissions had a comprehensive
paediatric, speech pathology and psychiatric assessment. RESULTS: Compared to the
general population, there was a significant history of developmental delay and
low birthweight, but only a slightly greater prevalence of antenatal problems.
Clumsiness (37%), severe speech and language disorder (32%), and hearing loss
(15%) were prominent. Only 25% had no history of comorbid medical or neurological
disorders. CONCLUSION: Children and adolescents presenting with moderate to
severe mental health morbidity may have pre-existing comorbid medical problems,
as well as unrecognised difficulties and impairments in other skills areas.
Multidisciplinary assessment and intervention should be an integral part of the
residential programme.
PMID- 9633977
TI - Carrier identification in X-linked immunodeficiency diseases.
AB - OBJECTIVE: Carrier identification in X-linked immunodeficiency disorders can be
based on the demonstration of non-random X inactivation (NRXI) in affected blood
cell lineages when growth is impaired in cells expressing the abnormal gene. We
examined the utility of seeking evidence of NRXI to test the carrier status of
women in families affected by X-linked severe combined immunodeficiency (XSCID)
and X-linked hypogammaglobulinaemia (XLH), to identify as carriers the mothers of
boys with SCID or hypogammaglobulinaemia whose phenotype suggested X-linkage and
to infer X-linkage in boys with SCID or hypogammaglobulinaemia whose disease was
not clearly X-linked on the basis either of family history or clinical and
immunological characteristics. METHODOLOGY: A polymerase chain reaction-based
method was used to amplify a polymorphic CAG repeat in the first exon of the
androgen receptor gene after selective digestion of the active X chromosome with
a methylation-sensitive enzyme, HpaII to distinguish between the paternal and
maternal alleles and to identify their methylation status. RESULTS:
Heterozygosity was found in 24 of 31 female subjects (77%). As anticipated, NRXI
could be demonstrated in all lymphoid cells studied from obligate carriers of
XSCID and an obligate carrier of XLH but not on a carrier of X-linked
immunodeficiency with hyper-IgM. The finding of NRXI in the mother of a boy with
a SCID variant showed her to be a carrier of XSCID and establishes that her son
has XSCID, not otherwise evident from available data. CONCLUSIONS: This PCR assay
provides a rapid method for carrier detection of X-linked immunodeficiencies, and
has allowed us to expand the phenotype of XSCID
PMID- 9633978
TI - Clonidine poisoning--an emerging problem: epidemiology, clinical features,
management and preventative strategies.
AB - OBJECTIVE: To ascertain whether the incidence of clonidine poisoning in children
has increased given the probable increase in clonidine use for treatment of
childhood behavioural disorders. METHODS: Cases of clonidine poisoning requiring
hospital admission between 1985-95 inclusive were reviewed and demographic data
pertinent to each admission were recorded. A literature review was also
performed, with particular emphasis on incidence, clinical presentation and
management of clonidine poisoning. RESULTS: There were 14 cases of clonidine
poisoning during the specified period eight cases presenting in the last 2 years.
These eight children or their siblings had been prescribed clonidine for
behavioural disorders. The most common signs at presentation were alteration of
conscious state (71%) and bradycardia (50%). Nine children were given activated
charcoal while seven cases underwent gastric lavage or induced emesis. Although
six children were admitted to intensive care, length of hospital stay was less
than 24 h in all cases and all had a favourable outcome. CONCLUSION: We concluded
that the incidence of clonidine poisoning had increased over the specified period
and that, based on our results, this was likely to be due to an increase in
clonidine use in childhood behavioural disorders. Based on our data and that from
literature review it was evident that there are inconsistencies in the management
of clonidine poisoning and that safety measures, namely packaging and education,
are inadequate given the increasing profile of clonidine use.
PMID- 9633979
TI - Cardiac manifestations in tuberous sclerosis: a 10-year review.
AB - OBJECTIVE: Tuberous sclerosis is a genetic disorder with multisystem involvement.
The aim of this study was to focus primarily on the cardiac aspects of this
condition. METHOD: This review included 10 children with tuberous sclerosis
presenting to our department during a 10-year period. RESULTS: From our data, 80%
were found to have cardiac involvement. There was an equal prevalence of
neurologic complications. CONCLUSIONS: Cardiac tumours and seizures were the most
common problems encountered. Whereas most patients had no symptoms referable to
the cardiovascular system and required no active intervention, many of those with
neurologic involvement needed appropriate treatment.
PMID- 9633980
TI - Child and parent perceptions of stimulant medication treatment in attention
deficit hyperactivity disorder.
AB - OBJECTIVE: To evaluate child and parent perceptions of treatment with stimulant
medication in a sample of children with attention deficit hyperactivity disorder
(ADHD). METHODOLOGY: Child and parent perceptions questionnaires were completed
for 102 subjects participating in a double-blind, crossover trial of
methylphenidate (MPH) and dexamphetamine (DEX). RESULTS: Most children viewed
medication effects favourably, although 12.7% and 18.8% of children reported
feeling worse than usual when taking MPH and DEX, respectively. There was
disagreement between the child's and parents' perceptions of response in over one
quarter of cases. Most disagreements involved parents viewing the child's
response favourably, but the child rating reporting an unfavourable outcome. Side
effects were the main determinant of children's perceptions of adverse response.
CONCLUSIONS: A substantial proportion of children with ADHD experience treatment
with stimulant medication adversely. Side-effects are the principal determinant
of negative child perceptions. Parental report is usually in agreement with child
report; however, parental report alone is not infallible in providing reliable
information regarding effects as experienced by the child.
PMID- 9633981
TI - Renal tuberculosis in an Australian-born child.
AB - This report describes a case of renal tuberculosis, complicated by hypertension
and ureteric obstruction, in a previously well Australian born child. Despite
antituberculous chemotherapy and ureteric stenting, there was a progressive loss
of renal function in the right kidney until surgical nephrectomy allowed full
recovery. A high level of clinical suspicion is necessary for a diagnosis of
genitourinary tuberculosis. Ureteric cicatrisation and obstruction occasionally
may occur with healing, and therefore serial renal tract imaging during treatment
is necessary to detect this complication.
PMID- 9633982
TI - Massive subdural haematoma: an unusual complication of septicaemia in preterm
very low birthweight infants.
AB - Non-traumatic massive subdural haematoma is a rare condition in newborn infants
and is usually associated with hereditary coagulation disorders or congenital
vascular malformation. Its occurrence in preterm very low birthweight infants
secondary to systemic bacterial infection has not been reported. We describe two
extremely preterm neonates who developed massive subdural haematoma as a result
of gram-negative septicaemia and disseminated intravascular coagulation. Both
infants suffered severe parenchymal cerebral injury and hydrocephalus. Clinicians
should be aware of this unusual and catastrophic complication if a very low
birthweight infant with severe sepsis and disseminated intravascular coagulation
suddenly deteriorates despite successful treatment with antibiotics. Radiological
imaging by cranial ultrasound or computed tomography scanning should be routinely
considered in all such infants for the detection of intracranial bleeding.
PMID- 9633983
TI - Transient erythroblastopenia of childhood associated with transient neurologic
deficit: report of a case and review of the literature.
AB - OBJECTIVE: Patients with transient erythroblastopenia of childhood (TEC) may also
have a transient neurologic disorder. We present a case history and propose a
mechanism for this syndrome. PATIENT AND METHODOLOGY: We describe a 20-month-old
girl with TEC and transient hemiparesis. Records from the period January 1993
through December 1994 were reviewed to identify other patients with TEC and to
determine whether neurologic deficits were noted in these cases. RESULTS: Of
seven patients diagnosed with TEC over a 2-year period, only one had a neurologic
deficit. This child's hemiparesis resolved within 24 h after the appearance of
her symptoms. Her TEC resolved within 4 weeks, without long-term sequelae. Our
experience and review of the literature suggest that focal neurologic deficits in
TEC patients are uncommon, transient, lack long-term sequelae, and usually
resolve prior to hematologic recovery. CONCLUSIONS: Previous reports suggested
that the anaemia resulting from TEC might induce neurologic deficits. We suggest
an alternative mechanism in which viral infection triggers a host immune response
that independently leads to both TEC and neurologic abnormalities. Future studies
should address the role of viral infection in TEC patients with focal
neuropathies.
PMID- 9633984
TI - Glutaric aciduria type 1: an underdiagnosed cause of encephalopathy and dystonia
dyskinesia syndrome in children.
AB - Two cases of glutaric aciduria type 1 (GA 1) are presented. GA 1 is probably
underdiagnosed and misdiagnosed, and may explain a proportion of cases of
extrapyramidal and 'postencephalitic' cerebral palsy. Most cases of GA 1 present
with a severe dystonic-dyskinetic syndrome following an acute encephalopathy.
Asymptomatic cases have also been described, complicating genetic counselling and
prenatal diagnosis. We raise awareness of GA 1 and stress that if clinically
suspected, immediate institution of therapy may reduce late morbidity. Moreover,
if recognised in the presymptomatic stage, early institution of treatment may
prevent the onset of neurological symptoms. GA 1 is an inborn error of lysine and
tryptophan catabolism, caused by deficiency of the enzyme, glutaryl coenzyme-A
dehydrogenase. Urine organic acid analyses may be negative. Blood acylcarnitine
profile has recently been employed as a more sensitive test but was negative in
both our patients. Enzyme assay remains the definitive diagnostic test.
PMID- 9633985
TI - Mycoplasma encephalitis--should we be thinking more about it?
PMID- 9633986
TI - Thyroglossal duct cyst or ectopic thyroid gland?
PMID- 9633987
TI - Emergency management skills of south Australian paediatric trainees.
PMID- 9633988
TI - Lest we forget acute epiglottitis.
PMID- 9633989
TI - Mechanism of action of diazaborines.
AB - The diazaborine family of compounds have antibacterial properties against a range
of gram-negative bacteria. Initially, this was thought to be due to the
prevention of lipopolysaccharide synthesis. More recently, the molecular target
of diazaborines has been identified as the NAD(P)H-dependent enoyl acyl carrier
protein reductase (ENR), which catalyses the last reductive step of fatty acid
synthase. ENR from Mycobacterium tuberculosis is the target for the front-line
antituberculosis drug isoniazid. The emergence of isoniazid resistance strains of
M. tuberculosis, a chronic infectious disease that already kills more people than
any other infection, is currently causing great concern over the prospects for
its future treatment, and it has reawakened interest in the mechanism of
diazaborine action. Diazaborines only inhibit ENR in the presence of the
nucleotide cofactor, and this has been explained through the analysis of the x
ray crystallographic structures of a number of Escherichia coli ENR-NAD+
diazaborine complexes that showed the formation of a covalent bond between the
boron atom in the diazaborines and the 2'-hydroxyl of the nicotinamide ribose
moiety that generates a noncovalently bound bisubstrate analogue. The
similarities in catalytic chemistry and in the conformation of the nucleotide
cofactor across the wider family of NAD(P)-dependent oxidoreductases suggest that
there are generic opportunities to mimic the interactions seen here in the
rational design of bisubstrate analogue inhibitors for other NAD(P)H-dependent
oxidoreductases.
PMID- 9633990
TI - Selective depletion of DNA precursors: an evolving strategy for potentiation of
dideoxynucleoside activity against human immunodeficiency virus.
AB - Human immunodeficiency virus type 1 (HIV-1) is wholly dependent on its host cell
for a variety of essential metabolites. Among the latter are the deoxynucleoside
5'-triphosphates (dNTPs) required for reverse transcription of the single
stranded RNA viral genome into double-stranded viral DNA. Since viral DNA
synthesis has an absolute requirement for all four dNTPs, restriction of a single
one of these is sufficient to inhibit HIV-1 replication. To date, this
therapeutic strategy has been most successful when depletion of the individual
dNTP is coupled with exposure to its corresponding chain-terminating
dideoxynucleoside (ddN). While several examples of such combined therapy have
been defined and studied in vitro, that which has been investigated most
extensively at both the laboratory and the clinical level is ddATP exposure
combined with dATP depletion [with dATP restriction being induced by the
ribonucleotide reductase inhibitor hydroxyurea (HU) and ddATP generated from its
prodrug 2',3'-dideoxyinosine (ddI)]. Several long-term clinical trials of the
hydroxyurea/2',3'-dideoxyinosine combination have been completed, with plasma
viral RNA being reduced to undetectable levels in a substantial fraction (one
third to one-half) of the patients treated. The major advantages of this and
analogous combinations discussed in this review are their low cost relative to
other current multiple drug protocols and their potential for retention of
activity against drug-resistant HIV mutants.
PMID- 9633991
TI - Alcohol-mediated increases in acetaminophen hepatotoxicity: role of CYP2E and
CYP3A.
AB - This commentary focuses on the roles of CYP3A and CYP2E in alcohol-mediated
increases in acetaminophen hepatotoxicity. CYP2E has been considered to be the
main form of P450 responsible for such toxicity in animals and humans. However,
CYP3A, which is also induced by alcohol, has been shown to have a greater
affinity for acetaminophen than CYP2E. Previous experiments implicating CYP2E in
alcohol-mediated increases in acetaminophen hepatotoxicity have used inhibitors
of this form of P450 that are now proving to be non-specific.
Triacetyloleandomycin (TAO) is a potent inhibitor of CYP3A that maintains
specificity in vitro over a large concentration range. In rats treated with
ethanol or the combination of ethanol and isopentanol, the major higher chain
alcohol in alcoholic beverages, TAO protects animals from increases in
acetaminophen hepatotoxicity, suggesting a major role of CYP3A. CYP2E may not
have a major role due to the rapid loss of induced levels in the absence of
continued exposure to ethanol. Knockout mice, which are being used to define the
role of particular proteins in biological responses, have been developed for
CYP2E1 and CYP1A2 but not CYP3A. Cyp2e1(-/-) and Cyp1a2(-/-) mice are more
resistant to acetaminophen hepatotoxicity than wild-type strains, even though the
amounts of the other forms of P450s are unaltered in the liver. These findings
suggest that the relative amounts of P450s and not just kinetic characteristics
determine their role in acetaminophen hepatotoxicity. The clinical implications
of the findings that CYP3A can have a major role in acetaminophen-mediated
hepatotoxicity are discussed.
PMID- 9633992
TI - Role of additional mutations outside the YMDD motif of hepatitis B virus
polymerase in L(-)SddC (3TC) resistance.
AB - L(-)SddC (3TC) has been shown to be the most promising nucleoside analogue used
for the treatment of hepatitis B virus (HBV) infection. Unfortunately, it has
been reported that about 12% of HBV-infected patients experience a recurrence of
HBV after a period of treatment with 3TC. Point mutations were detected in the
HBV polymerase of those viruses from 3TC-resistant patients. A common mutation
occurred at methionine in the YMDD motif. In this report, we present mutants that
were generated from the HBV genome (adr subtype) by site-directed mutagenesis
based on clinical reports from other investigators. With the transient
transfection system, it was found that by changing methionine to valine or
isoleucine at the YMDD motif, the viral DNA replication would be more than 100
fold less efficient than that of the wild-type virus. Some additional mutations
outside the YMDD motif could enhance the replication of the virus containing a
YMDD mutation. Various levels of resistance to 3TC were observed in HBV mutants
containing point mutations both inside and outside the YMDD motif. These results
suggest that the mutations outside the YMDD motif compensate the YMDD mutation to
some extent for the viral replication and may also contribute to clinical viral
resistance to 3TC.
PMID- 9633993
TI - Elevation of endogenous nucleophiles in rat lung by cysteine and glutathione
esters in vitro.
AB - In this study, we have compared the uptake of L-cysteine (L-CySH), D-cysteine (D
CySH), L-cysteine isopropyl ester (L-CIPE) and D-cysteine isopropyl ester (D
CIPE) in rat lung slices and tracheal sections and determined the effectiveness
of glutathione (GSH), GSH isopropyl monoester, GSH isopropyl diester, gamma
glutamylcysteine (gamma-glu-cys) isopropyl monoester and gamma-glu-cys isopropyl
diester to elevate and prolong intracellular GSH concentrations in rat lung
slices. Lung slices were incubated with 1.0 mM of thiol and the concentrations
determined intracellularly and extracellularly with time. Slices incubated with
GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester had cellular GSH
concentrations increased by up to 60%, 95% and 58%, respectively, whereas GSH
isopropyl monoester and gamma-glu-cys isopropyl monoester did not increase the
intracellular GSH concentration. Extracellularly, the GSH concentration had
decreased by 15%, GSH isopropyl diester by 27%, gamma-glu-cys isopropyl diester
by 66% and both isopropyl monoesters by over 90% at 120 min. Lung slices and
tracheal sections incubated with L- or D-CySH at 37 degrees had increased
cellular concentrations of L- and D-CySH which ranged between 0.88-1.25 nmol mg(
1) and 1.35-2.25 nmol mg(-1) , respectively. Reducing the incubation temperature
to 4 degrees had little effect on the accumulation of D-CySH; however, L-CySH
concentrations increased progressively in the trachea and lung to reach 2.73 and
2.63 nmol mg(-1) at 90 min, respectively. Lung slices incubated with L- or D-CIPE
had increased L- or D-CySH concentrations up to a max of 13.7 and 11.1 nmol mg(
1) and tracheal sections up to a max of 5.56 and 11.09 nmol mg(-1). In the lung
slice medium, L- and D-CIPE levels had decreased by 75.2% and 74.0% at 90 min,
respectively, and from the tracheal section medium, L- and D-CIPE concentrations
had decreased by 66.7% and 32.7%, respectively. Preincubation of lung slices and
tracheal sections with the carboxylesterase inhibitor, bis (p-nitrophenyl)
phosphate (BNPP), almost completely prevented the disappearance of L- and D-CIPE
extracellularly and greatly reduced the appearance of cellular L- and D-CySH.
GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester elevated and
prolonged GSH concentrations in rat lung slices, but GSH isopropyl monoester and
gamma-glu-cys isopropyl monoester did not increase GSH levels. The uptake of L
CySH, but not D-CySH, is temperature sensitive in rat lung slices and tracheal
sections and carboxylesterases appear to have a major influence on the uptake and
metabolism of L- and D-CIPE by rat lung slices and tracheal sections.
PMID- 9633994
TI - In vivo radioprotective effects of oltipraz in gamma-irradiated mice.
AB - Previous studies in this laboratory have shown that oltipraz (Olt), a
chemopreventive agent, enhances radiation(Rad)-inducible glutathione S
transferase (GST) and microsomal epoxide hydrolase (mEH) expression in the liver.
The present study was designed to investigate the in vivo radioprotective effect
of Olt in ICR mice exposed to a lethal dose of Rad. The 30-day survival rate of
mice irradiated at the dose of 8 Gy was substantially increased to 91% by Olt
pretreatment (100 mg/kg/day for 2 days), compared with 48% in animals irradiated
alone. Light microscopic examinations revealed that exposure of mice to 8 Gy of
gamma-ray Rad resulted in hepatocyte degeneration in the surviving animals from
Day 1 through Day 22 after irradiation with certain degrees of necrosis observed
at early times, whereas Olt treatment provided protection of the liver against
irradiation with no hepatic necrosis noted. Mice irradiated at the dose of 8 Gy
exhibited time-related decreases in the white blood cell (WBC), red blood cell
(RBC), and platelet counts with maximal reduction noted at Day 10. Animals
irradiated with Olt treatment showed no difference in peripheral blood cell
counts or in the ratio of myeloid to erythroid bone marrow cells, compared with
those irradiated alone. Northern RNA blot analysis showed that treatment of mice
with Olt at the dose of 100 mg/kg in combination with 8 Gy irradiation resulted
in 12-fold increases in hepatic mEH and mGSTA3 mRNA levels at 24-hr post
treatment, whereas mGSTP1 mRNA levels were not altered. The mRNA levels for mEH
and mGSTA3 were elevated after exposure of animals to both Olt and 8 Gy-gamma ray
to a greater extent than after irradiation alone. The enhanced survival rate
(91%) in 8 Gy-irradiated animals after treatment with Olt (100 mg/kg/day for 2
days) was completely reversed by concomitant pretreatment with dexamethasone
(Dexa) (0.1 and 1 mg/kg/day for 2 days), a known inhibitor of mEH and GST
expression, resulting in a 42% and 28% survival rate, respectively. Mice
irradiated after dexamethasone treatment at a dose of 1 mg/kg showed a reduced
mean survival time compared with those treated with 0.1 mg/kg of dexamethasone (9
vs 14 days). The current study demonstrates that Olt is effective in increasing
the survival rate of mice against ionizing Rad and that protective effects of Olt
associated with enhanced expression of mEH and GST genes may represent its
radioprotective efficacy.
PMID- 9633995
TI - Effects of iodotyrosines, thyronines, iodothyroacetic acids and thyromimetic
analogues on in vitro copper-induced oxidation of low-density lipoproteins.
AB - We studied the effect of different thyroid compounds [(I2, monoiodo-L-tyrosine
(MIT), diiodo-L-tyrosine (DIT), L-thyronine (T0), 3,5-diiodo-L-thyronine (T2),
3,5,3'-triiodo-L-thyronine (T3), 3,3',5'-triiodo-L-thyronine (rT3), 3,5,3',5'
tetraiodo-L-thyronine (T4), 3,5-diiodothyroacetic acid (TA2), 3,5,3'
triiodothyroacetic acid (TA3) and 3,5,3',5'-tetraiodothyroacetic acid (TA4)] or
thyromimetics [(3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'
isopropyl-thyroacetic acid (IpTA2)] on in vitro copper-induced oxidation of low
density lipoproteins (LDL). Human native LDL (0.05 g protein/L) oxidation was
induced by 2.5 micromol/L of CuCl2. Conjugated dienes were measured
spectrophotometrically for up to 10 hr. The length of the lag phase (Tlag),
maximum velocity of the reaction (Vmax) and the maximum amount of generated
dienes were obtained from kinetic data. T3 increased Tlag and decreased Vmax with
a dependence upon concentration (0 to 3 micromol/L). There was no difference
between the Dmax obtained with Cu2+ alone or in the presence of the various
compounds (1 micromol/L). I2, MIT and DIT did not modify any parameter of the
oxidation kinetic. T0 and T2 had the same antioxidant efficiency as T3, whereas
T4 only decreased Vmax. rT3 increased Tlag less than did T3, whereas DIMIT was
the thyronine that had the most important effect. TA2 and TA, were the most
efficient antioxidant compounds. TA4 decreased Tlag less than TA3 did, whereas
IpTA2 had an effect weaker than that of the physiological acetic derivatives. The
data suggest that thyroid hormones and derivatives have LDL-antioxidant
properties, their importance being related to their 4'-hydroxy diphenyl ether
structure and depending upon the nature and the position of substituents in this
structure.
PMID- 9633996
TI - Differential effects of monensin on asialoglycoprotein receptor function after
short-term ethanol administration.
AB - Chronic ethanol consumption is associated with multiple impairments in receptor
mediated endocytosis (RME) by the hepatic asialoglycoprotein receptor (ASGP-R).
Previous work on this receptor has shown that its activity can be perturbed by
the carboxylic ionophore monensin. This agent has been shown to preferentially
affect receptor-ligand dissociation and receptor redistribution of one subset
(State 2) of ASGP-R, while receptor function in a second subset (State 1
receptors) is unaffected. In the present study, we examined the effect of
monensin on ASGP-R activity and intracellular receptor-ligand dissociation after
7-10 days of ethanol feeding, a time when we have shown altered ASGP-R function
in ethanol-fed animals. Hepatocytes from male Wistar rats (fed an ethanol
containing or control diet) were utilized. Ethanol administration decreased total
ligand binding by 35-40% (P < 0.01) without a change in receptor protein content.
After monensin treatment, surface receptors on cells from control animals were
inactivated and redistributed to the cell interior. In cells from ethanol-fed
animals, a similar pattern of monensin-induced inactivation was shown, but no
redistribution occurred. Intracellular receptor-ligand dissociation was impaired
in both cell types, although the monensin-induced effect on dissociation was
significantly less dramatic (two-fold) in the hepatocytes from ethanol-fed
animals as compared with controls. Thus, although receptors on both cell types
were susceptible to monensin, cells from the ethanol-fed animals were less
vulnerable to the added effects of this agent. Since monensin affects functioning
of State 2, but not State 1 receptors, a very early effect of ethanol may be a
preferential impairment in the State 2 receptor population.
PMID- 9633997
TI - 19F NMR study of the uptake of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil
in erythrocytes: evidence of transport by facilitated and nonfacilitated
pathways.
AB - The 19F NMR resonances of intra- and extracellular 2'-fluoro-5-methyl-beta-L
arabinofuranosyluracil (L-FMAU) in suspensions of human erythrocytes are well
resolved. This phenomenon allows its transport behavior to be monitored in a 19F
NMR time-course experiment. The rate of L-FMAU uptake at 25 degrees in a
suspension containing L-FMAU at an initial extracellular concentration of 4 mM
was 7.6 +/- 1.0 x 10(-7) pmol cell(-1) sec(-1) (N = 5). Concentration-dependent
uptake studies of L-FMAU indicate the existence of both saturable and
nonsaturable transport mechanisms, with a Km for the saturable uptake of
approximately 1 mM. Although the transport of L-FMAU at 25 degrees was inhibited
significantly (54-65%) by nitrobenzylthioinosine (NBTI) and dipyridamole,
consistent with the participation of the nucleoside transporter, these inhibitors
did not achieve complete blockage of L-FMAU uptake. The participation of the
nucleobase transporter in L-FMAU uptake was ruled out by the absence of
competition with uracil uptake, and by the lack of inhibition by papaverine. In
addition, the NBTI-insensitive uptake of L-FMAU was not affected by pretreatment
of the cells with the sulfhydryl reagent, p-chloromercuriphenylsulfonic acid
(pCMBS). However, the NBTI- and dipyridamole-insensitive transport of L-FMAU was
found to increase upon treatment of the erythrocytes with butanol, an agent that
affects membrane fluidity. The partition coefficient of L-FMAU in
octanol/phosphate-buffered saline determined by absorption spectrophotometry was
0.31. These data indicate that under the conditions of the studies, L-FMAU uptake
by erythrocytes proceeds by both the nucleoside transporter and nonfacilitated
membrane diffusion.
PMID- 9633998
TI - Regulation of cyclo-oxygenase gene expression in rat smooth muscle cells by
catalase.
AB - We have studied, in detail, the effect of catalase, one of the naturally
occurring antioxidant enzymes, on the expression of cyclo-oxygenase (COX) mRNA
and protein in rat aortic smooth muscle cells (RASMC). The activity of COX enzyme
within the cells was also determined. Catalase either alone or in combination
with interleukin-1beta (IL-1beta) enhanced mRNA and protein expression for cyclo
oxygenase 2 (COX-2) in a concentration-dependent manner. However, it did not
affect the expression of mRNA or protein for cyclo-oxygenase 1 (COX-1). The
expression of mRNA for COX-2 induced by catalase was blocked completely by
actinomycin D (ACT) or cycloheximide (CHX). In comparison, expression of mRNA for
COX-2 stimulated by IL-1beta was inhibited by actinomycin D, but not by
cycloheximide. This suggests that induction of the synthesis of mRNA for COX-2 by
catalase and IL-1beta involves different mechanisms. In particular, the induction
of mRNA for COX-2 by catalase requires on-going protein and RNA synthesis, but
the induction following exposure to IL-1beta does not. The increase in expression
of mRNA for COX-2 induced by catalase may be related to the ability of catalase
to stimulate cyclic AMP response element (CRE) and NF-IL6 transcription factors,
but not nuclear factor kappa B (NF-kappaB), for electrophoretic mobility shift
assays (EMSA) showed that catalase enhanced nuclear factor binding to cyclic AMP
response element and NF-IL6 but not to NF-kappaB. Catalase exerted a biphasic
effect on prostaglandin synthesis. At low concentrations it enhanced
prostaglandin production, but at high concentrations it tended to inhibit it.
These findings suggest that catalase has differential and multiple effects on COX
expression and activity in rat aortic smooth muscle cells.
PMID- 9633999
TI - Inhibitory monoclonal antibody to human cytochrome P450 2B6.
AB - The human cytochrome P450 2B6 metabolizes, among numerous other substrates,
diazepam, 7-ethoxycoumarin, testosterone, and phenanthrene. A recombinant
baculovirus containing the human 2B6 cDNA was constructed and used to express 2B6
in Sf9 insect cells. The 2B6 was present at 1.8 +/- 0.4% of the total cellular
protein and was purified to a specific content of 13.3 nmol/mg protein. Mice were
immunized with the purified 2B6, and a total of 811 hybridomas were obtained from
the fusion of NS-1 myeloma cells and spleen cells of the immunized mice.
Monoclonal antibodies (MAbs) from 24 of the hybrids exhibited immunobinding to
2B6 as determined by ELISA. One of the MAbs, 49-10-20, showed a strong
immunoblotting activity and was highly inhibitory to 2B6 enzyme activity. MAb 49
10-20 inhibited cDNA-expressed 2B6-catalyzed metabolism of diazepam,
phenanthrene, 7-ethoxycoumarin, and testosterone by 90-91%. MAb 49-10-20 showed
extremely high specificity for 2B6 and did not bind to 17 other human and rodent
P450s or inhibit the metabolism of phenanthrene catalyzed by human 1A2, 2A6, 2C8,
2C9, 2D6, 2E1, 3A4, and 3A5. MAb 49-10-20 was used to determine the contribution
of 2B6 to the metabolism of phenanthrene and diazepam in human liver. In ten
liver samples, MAb 49-10-20 inhibited phenanthrene metabolism variably by a wide
range of 8-42% and diazepam demethylation by 1-23%. The degree of inhibition by
the 2B6 specific MAb 49-10-20 defines the contribution of 2B6 to phenanthrene and
diazepam metabolism in each human liver. This technique using inhibitory MAb 49
10-20 determines the contribution of 2B6 to the metabolism of its substrates in a
human tissue containing multiple P450s. This study is a prototype for the use of
specific and highly inhibitory MAbs to determine individual P450 function.
PMID- 9634000
TI - Increased concentrations of methylated 6-mercaptopurine metabolites and 6
thioguanine nucleotides in human leukemic cells in vitro by methotrexate.
AB - The effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism was
studied in four human leukemic cell lines in vitro. CCRF-CEM, WI-L2, TBJ, and HL
60 all expressed thiopurine methyltransferase (TPMT) activity. The cells were
grown in horse serum-supplemented RPMI 1640 medium to which was added 4 microM of
6-MP or 4 microM of 6-MP and 20 nM of MTX. The presence of MTX resulted in a 2.1
, 1.7-, 2.4- and 8-fold increase in the concentrations of methylmercaptopurine
ribonucleotides (MMPRP) in CEM, WI-L2, TBJ, and HL-60 cells, respectively (P <
0.0008). The concentrations of 6-thioguanine nucleotides (6 TGN) increased 1.9-,
1.4-, 2.4- and 1.9-fold in the same cell lines (P < 0.02). The four cell lines
differed with respect to the effect of MTX on the consumption of 6-MP from the
medium; CEM consumed more 6-MP and WI-L2 less 6-MP from media containing MTX than
from media containing 6-MP only (P = 0.005 and 0.02, respectively). MTX did not
affect the consumption of 6-MP by TBJ cells (P = 0.17). Media in which HL-60
cells had been grown did not contain detectable amounts of 6-MP at the end of the
experiment. The simultaneous increase in methylated 6-MP metabolites and 6-TGN
represents a possible explanation for the synergism of MTX and 6-MP; however, the
clinical importance of increased MMPRP remains to be elucidated.
PMID- 9634001
TI - Suppression of C/EBPalpha and induction of C/EBPbeta by 2,3,7,8
tetrachlorodibenzo-p-dioxin in mouse adipose tissue and liver.
AB - We examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on two
transcription factors, CAAT/enhancer binding protein-alpha (C/EBPalpha) and beta
(C/EBPbeta), involved in the coordination of gene expression in adipose and
liver. A single dose of TCDD (100 microg/kg) to male C57BL mice resulted in a
time- and dose-dependent decrease in the level of C/EBPalpha mRNA in adipose
tissue and liver, and a reciprocal increase in C/EBPbeta mRNA. Gel shift analysis
using hepatic nuclear extracts from control and TCDD-treated mice and an
oligonucleotide containing a C/EBP recognition element revealed a time-dependent
change in DNA-protein complexes formed. Bands corresponding to C/EBPalpha, as
determined by supershift analysis, diminished in TCDD-treated animals over a 7
day time period, whereas two new bands corresponding to C/EBPbeta, not present in
control extracts, were increased significantly in treated samples. TCDD induced
C/EBPbeta mRNA in wild-type mouse hepatoma cells, but not in aryl hydrocarbon
receptor (AhR) nuclear translocator-deficient hepatoma cells. Induction in wild
type hepatoma cells was antagonized effectively by a molar excess of alpha
naphthoflavone. These results showed that TCDD caused rapid, reciprocal changes
in C/EBPalpha and C/EBPbeta mRNAs and DNA binding in the adipose and liver of
male C57BL mice and induced C/EBPbeta in hepatoma cells in an AhR-dependent
manner. C/EBPs play vital roles in the coordination of energy homeostasis, and
their alteration by TCDD may provide insight into the mechanism by which TCDD
perturbs energy storage and utilization in vivo.
PMID- 9634002
TI - Determination of deoxyribonucleoside triphosphate pool sizes in ribonucleotide
reductase cDNA transfected human KB cells.
AB - Ribonucleotide reductase (RR) is a rate-limiting enzyme in DNA synthesis, which
is responsible for controlling deoxyribonucleoside triphosphate (dNTP) pool size.
It has been shown that transfection of RR M2 cDNA in human KB cells (M2-D clone)
results in overexpression for the M2 subunit and resistance to hydroxyurea (HU).
In this study, dNTP pool assays were performed to measure the pool sizes in six
cell lines: two controls, three transfectants, and drug-induced HU-resistant
(HUR) cells. Total dNTP levels among the six cell lines rose in the following
order: KB wild-type, KB vector-only transfectant, M1 cDNA transfectant, M2 cDNA
transfectant, M1/M2 cDNA transfectant, and HU-induced resistant clone. The dCTP
levels of the cells mimicked the total dNTP pools on a smaller scale. The
significant increases in the dCTP pool sizes of the M2-D, X-D, and HUR clones
were proportional to their respective increases in RR activity. Relative to all
other transfectants, the M1-D clone demonstrated lower dCTP levels but increased
dATP pools. The M1-D clone demonstrated a significant resistance to dNTP
inhibition of RR activity compared with the control KB wild-type cells. In
contrast, a profound inhibition of dCTP and a decreased sensitivity to dATP
inhibition was observed in M2-D, X-D, and HUR clones. In summary, M2 cDNA
transfectants and HUR clones had increased RR activity as well as expanded dNTP
pools, particularly dCTP, when compared with wild-type KB cells. These data
provide evidence for the intertwined relationship between RR activity and dNTP
pools.
PMID- 9634003
TI - In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate.
AB - Aminoguanidine (AG) is considered to be a promising compound for the treatment of
diabetic complications. We examined the in vitro and in vivo formation of Schiff
bases of AG with pyridoxal 5'-phosphate (PLP) and pyridoxal (PL). AG reacted in
vitro far more rapidly with PLP to form a Schiff base (PLP-AG) than with PL to
form another Schiff base (PL-AG). Administration of AG at 7 mM in drinking water
for 18 weeks caused the formation of PLP-AG in the liver and kidney of mice (12.1
+/- 1.6 and 3.8 +/- 0.64 nmol/g of tissue, respectively, mean +/- SD, N = 6). The
amount of PLP in the liver of mice AG administered was significantly lower than
that of control mice (4.0 +/- 1.4 vs 17.4 +/- 1.3 nmol/g of wet tissue, mean +/-
SD, N = 6). Simultaneous administration of pyridoxine (1 mM in drinking water)
with AG (7 mM in drinking water) did not ameliorate the decrease in tissue PLP
and caused the excess formation of PLP-AG. The results suggest that attention
should be paid to the deficiency of tissue PLP in the clinical use of AG.
PMID- 9634004
TI - Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human
cells.
AB - Activation of purine nucleoside analogs by Escherichia coli purine nucleoside
phosphorylase (PNP) is being evaluated as a suicide gene therapy strategy for the
treatment of cancer. Because the mechanisms of action of two toxic purine bases,
6-methylpurine (MeP) and 2-fluoroadenine (F-Ade), that are generated by this
approach are poorly understood, mechanistic studies were initiated to learn how
these compounds differ from agents that are being used currently. The
concentration of F-Ade, MeP, or 5-fluorouracil required to inhibit CEM cell
growth by 50% after a 4-hr incubation was 0.15, 9, or 120 microM, respectively. F
Ade and MeP were also toxic to quiescent MRC-5, CEM, and Balb 3T3 cells.
Treatment of CEM, MRC-5, or Balb 3T3 cells with either F-Ade or MeP resulted in
the inhibition of protein, RNA, and DNA syntheses. CEM cells converted F-Ade and
MeP to F-ATP and MeP-ribonucleoside triphosphate (MeP-R-TP), respectively. The
half-life for disappearance of HeP-ribonucleoside triphosphate from CEM cells was
approximately 48 hr, whereas the half-lives of F-ATP and ATP were approximately 5
hr. Both MeP and F-Ade were incorporated into the RNA and DNA of CEM cells. These
studies indicated that the mechanisms of action of F-Ade and MeP were quite
different from those of other anticancer agents, and suggested that the
generation of these agents in tumor cells by E. coli PNP could result in
significant advantages over those generated by either herpes simplex virus
thymidine kinase or E. coli cytosine deaminase. These advantages include a novel
mechanism of action resulting in toxicity to nonproliferating and proliferating
tumor cells and the high potency of these agents during short-term treatment.
PMID- 9634005
TI - Concentrating capacity of the human reduced folate carrier (hRFC1) in human ZR-75
breast cancer cell lines.
AB - Human RFC1 (hRFC1) transfected in transport-deficient methotrexate MTXR(R)ZR-75-1
human breast carcinoma cells (MTX(R)ZR-75/RFC) were used to investigate the
impact of hRFC1 overexpression on influx and concentrative transport of
methotrexate (MTX). Eight-fold overexpression of hRFC1, as determined by northern
analysis, resulted in a 4-fold increase in MTX influx accompanied by a 2.4-fold
increase in the steady-state level of free drug as compared with wild-type ZR-75
1 cells when the extracellular MTX level was 0.5 microM. When extracellular MTX
was increased to 10 microM, the increase in influx equaled the increase in the
transmembrane chemical gradient for MTX in the transfectant relative to wild-type
cells. By 50 min, approximately 16-20 and 25% of the intracellular 3H represented
MTX polyglutamates by HPLC analysis at [MTX]e = 0.5 and 10 microM in wild-type
and transfected cells, respectively. Overexpression of hRFC1 enhanced sensitivity
to MTX in MTX(R)ZR-75-1 cells by more than 250-fold. The data indicate that
overexpression of hRFC1 in human cells results in comparable increases in influx
and transmembrane gradients. This is different from what was reported when mouse
RFC1 was transfected into murine leukemia cells, resulting in large, more
symmetrical increases in the MTX bidirectional transport kinetics with a much
smaller change in steady-state levels. The changes in the human cells transfected
with hRFC1 however, were similar to what has been observed by other investigators
when RFC1 expression is increased by low folate selective pressure.
PMID- 9634006
TI - Stimulation of melanogenesis in a human melanoma cell line by bistratene A.
AB - The polyether toxin, bistratene A, induced morphological and functional
differentiation of a human melanoma cell line (MM96E). The cells became blocked
at the G2/M transition and elaborated a number of processes. Tyrosinase activity
and melanin content were substantially increased. Northern blot analysis showed
up-regulation of mRNA for several genes known to be involved in melanin
biosynthesis (pmel17, pmel34, and tyrosinase related proteins, TRP-1 and TRP-2).
Bistratene A induced the phosphorylation of several proteins as assessed by 2D
gel electrophoresis and one of these was identified as stathmin (oncoprotein 18),
a cell-cycle regulated phosphoprotein. Bistratene A specifically induced the
translocation of protein kinase Cdelta (PKCdelta) from a soluble to a particulate
fraction without affecting other isoforms. These results implicate a role for
protein kinase Cdelta in the induction of differentiation of this human melanoma
cell line.
PMID- 9634007
TI - O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6
benzylguanine derivatives and their rate of hydrolysis by cellular esterases.
AB - To modulate the bioavailability and perhaps improve the tumor cell selectivity of
O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester
derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT
inactivators and as substrates for cellular esterases. The potential prodrugs
examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7-
and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9
esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8
bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure
AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at
least 75 times less potent than the corresponding benzylated purine against the
pure human AGT. In contrast, the activities of esters and their respective
benzylated purine were similar in crude cell extracts and in intact cells. The
increase in potency of esters in cellular extracts could be explained by a
conversion of the respective prodrug to the more potent benzylated purine in the
presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of
liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater
than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor
cell hydrolysis of the esters varied considerably as a function of cell type and
prodrug structure. These data suggest that these or related prodrugs may be
advantageous for selective AGT inactivation in certain tumor types.
PMID- 9634008
TI - Induction of apoptosis in glioblastoma cells by inhibition of protein kinase C
and its association with the rapid accumulation of p53 and induction of the
insulin-like growth factor-1-binding protein-3.
AB - Increased protein kinase C(alpha) (PKC(alpha)) expression in glioblastoma cells
is associated with proliferation and resistance to drug-induced apoptosis by an
undefined anti-apoptotic pathway. To clarify the role of PKC in apoptosis, we
have investigated the effect of the selective PKC inhibitor Ro 31-8220 (3-[1-[3
(amidinothio)propyl]-3-indolyl]-4-(1-methyl-3-indolyl)-1H -pyrrole-2,5-dione
methanesulfonate) in two glioblastoma cell lines whose proliferation is dependent
on high levels of PKC(alpha). U-87 and A172 cells treated with an IC50 of Ro 31
8220 exhibited nucleosomal DNA fragmentation that coincided with an increase in
the number of apoptotic cells. This effect was preceded by the rapid nuclear
accumulation of wild-type p53 within 2 hr, and an increased level of the pro
apoptotic protein, insulin-like growth factor-1-binding protein-3, (IGFBP3) but
not other p53-regulated proteins such as p21WAF1 or Bax. Accumulation of p53 was
also associated with the hypophosphorylated and activated form of the
retinoblastoma tumor suppressor protein (RB) at later times after treatment.
These results suggest that PKC(alpha) suppresses apoptosis in glioblastoma cells
primarily by restricting the accumulation of p53 and the expression of insulin
like growth factor-1-binding protein, as well as by maintaining RB in an inactive
hyperphosphorylated state.
PMID- 9634009
TI - Transport of quercetin and its glucosides across human intestinal epithelial Caco
2 cells.
AB - There is mounting evidence from human epidemiological, animal in vivo, and in
vitro studies to suggest beneficial effects related to the consumption of
quercetin and its glucosides. However, there is limited knowledge on the oral
bioavailability of these natural products. This study examined the intestinal
epithelial membrane transport of quercetin, quercetin 4'-glucoside, and quercetin
3,4'-diglucoside, using the Caco-2 human colonic cell line, a model of human
intestinal absorption. The apparent permeability (Papp) of each agent was
measured in both apical to basal and basal to apical directions. The apical to
basolateral flux of quercetin, Papp 5.8 +/- 1.1 x 10(-6) cm x sec(-1) (mean +/-
SEM), was more than 10-fold higher than for the paracellular transport marker
mannitol, 0.48 +/- 0.09 x 10(-6) cm x sec(-1) (P < 0.01). Under identical
conditions, the Papp for the transcellular marker propranolol was about 5-fold
higher than for quercetin (P < 0.001). Interestingly, the reverse, basolateral to
apical, flux of quercetin (Papp 11.1 +/- 1.2 x 10(-6) cm x sec(-1)) was almost 2
fold higher than the apical to basolateral flux (P < 0.001). In similar
experiments, quercetin 4'-glucoside demonstrated no absorption, Papp < 0.02 x 10(
6) cm x sec(-1) in the apical to basal direction, but did demonstrate basal to
apical flux, Papp 1.6 +/- 0.2 x 10(-6) cm x sec(-1). Quercetin 3,4'-diglucoside
showed a low apical to basolateral transport (Papp 0.09 +/- 0.03 x 10(-6) cm x
sec(-1)); its reverse, basolateral to apical, transport was, however, 4-fold
higher (P < 0.05). In these cells, glucose was actively transported with an
apical to basolateral Papp of 36.8 +/- 1.1 x 10(-6) cm x sec(-1). These
observations suggest facile absorption of quercetin through the human intestinal
epithelium, but contrary to a previous proposal, they do not support an active
transport process for quercetin glucosides.
PMID- 9634010
TI - Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS
mice as a model of human carnitine transporter deficiency.
AB - Recently, the marked decline in renal carnitine reabsorption has been thought to
account fotr the systemic carnitine deficiency in juvenile visceral steatosis
(JVS) mice. We have conducted a kinetic analysis using embryonic fibroblasts
derived from normal, heterozygous, and homozygous jvs mice and found that the
high-affinity carnitine transporter (Km = 5.5 microM), which shows Na+ and
temperature dependency and stereospecificity, is defective in homozygous jvs
mice. Moreover, a gene dose-dependent decrease of carnitine transport activity,
which was due to a decrease in the number of the transporter molecules, was found
in heterozygous jvs mice. Similar phenomena have been observed in human primary
carnitine deficiency. Therefore, JVS mice may be useful for understanding this
extremely rare human hereditary disorder.
PMID- 9634011
TI - Inhibition of cholinesterase-associated aryl acylamidase activity by
anticholinesterase agents: focus on drugs potentially effective in Alzheimer's
disease.
AB - The potency of a series of anticholinesterase (anti-ChE) agents and serotonin
related amines as inhibitors of the aryl acylamidase (AAA) activity associated
with electric eel acetylcholinesterase (AChE) (EC 3.1.1.7) and horse serum
butyrylcholinesterase (BuChE) (EC 3.1.1.8) was examined and compared with the
potency of the same compounds as ChE inhibitors. Neostigmine, physostigmine, BW
284C51, (+/-)-huperzine A, E2020, tacrine, edrophonium and heptyl-physostigmine
were, in that order, the most potent in inhibiting eel AChE-associated AAA
activity, their inhibitor constant (Ki) values being in the range 0.02-0.37
microM. The rank order of the same compounds as AChE inhibitors basically
paralleled that of AAA, although they were in general stronger on AChE (Ki =
0.001-0.05). The peripheral anionic site inhibitors propidium and gallamine were
inactive on AChE-associated AAA. Serotonin and its derivatives were slightly
stronger on AAA (Ki = 7.5-30 microM) than on AChE (Ki = 20-140 microM). Tacrine
(IC50 = 0.03 microM), diisopropylfluorophosphate (IC50 = 0.04 microM), heptyl
physostigmine (IC50 = 0.11 microM), physostigmine (IC50 = 0.15 microM) and tetra
iso-propylpyrophosphoramide (iso-OMPA) (IC50 = 0.75 microM) were the most potent
in inhibiting horse serum BuChE-associated AAA activity. Serotonin and related
amines were very weak on BuChE-associated AAA activity. These results indicate
that the inhibitory potencies of the active site anti-ChE agents on the AAA
activity associated with eel AChE and horse serum BuChE are closely correlated
with their action on the respective ChE. In addition, the efficacy of tacrine,
E2020, heptyl-physostigmine and (+/-)-huperzine A in the treatment of Alzheimer's
disease is unlikely to be related to the action of these drugs on ChE-associated
AAA.
PMID- 9634012
TI - Standardization and definitions in lower urinary tract dysfunction in children.
International Children's Continence Society.
PMID- 9634013
TI - Desmopressin in the treatment of severe nocturnal enuresis in adolescents--a 7
year follow-up study.
AB - OBJECTIVES: To evaluate the role of long-term oral desmopressin (over a 7-year
follow-up) in refractory enuretics, particularly in assessing the potential
curative effect, and to analyse the results for specific types of patient to
obtain clues about possible mechanisms of cure. PATIENTS AND METHODS: The effect
of oral desmopressin was investigated in 25 adolescents (aged 11-21 years) with
severe monosymptomatic nocturnal enuresis. The long-term study consisted of two
12-week treatment periods, with the efficacy of the drug assessed as the
reduction in the number of wet nights per week. Subsequently, the patients were
followed-up for up to 7 years. Close contact was maintained with the families
over this period ('good doctoring' approach). At 3-, 5- and 7-year intervals
after completing the study, patients were assessed for dryness, frequency,
treatment and sleeping habits, using postal questionnaires and telephone follow
up. RESULTS: At the end of the long-term study, 35% of the patients remained dry
without therapy. Within 2 years of ending treatment, 15 patients were dry,
compared with an expected estimate of six by spontaneous resolution, and after 7
years, 19 patients were cured. Nocturia occurred in 75% of the enuretic patients
but in only 5% of the healthy controls. CONCLUSIONS: Active treatment of primary
nocturnal enuresis with oral desmopressin has a clinically significant effect on
the cure rate, which is maintained after ceasing therapy. The cure rate was
higher than would be expected from spontaneous recovery alone during the first 2
years of the study and there was a significant further increase in the cure rate
7 years after ending therapy, again greater than the expected spontaneous cure
rate. There also seemed to be a better response to treatment when it was
prolonged. Furthermore, this therapy is safe when administered in the long-term.
PMID- 9634014
TI - Long-term use and tapered dose reduction of intranasal desmopressin in the
treatment of enuretic children.
AB - OBJECTIVE: To determine the time taken to achieve complete dryness, the
management of desmopressin dosage to reduce the relapse rate, the mean dosage in
those responding and any side effects of long-term treatment. PATIENTS AND
METHODS: Enuretic children (155, 68% boys and 32% girls, mean age 8 years, range
5-19) were treated with desmopressin and assessed. Treatment (intranasal spray)
was started with 20 microg desmopressin and titrated to 40 microg (maximum 50
microg) after 2 days if the child did not become dry within 48 h. The maximum
dosage was maintained for at least 4-6 weeks. After 4 weeks of complete dryness,
the dosage was reduced by 10 microg initially, and after each additional 4 dry
weeks, by a further 10 microg; medication was stopped only after 4 dry weeks at
10 microg. RESULTS: Of the children, 85% responded to intranasal desmopressin
therapy; 71% achieved complete dryness with no relapses, remaining dry with no
further treatment, 7% achieved dryness after relapses during or after therapy, 7%
improved (no more than two wet nights per week) and 15% did not respond to
therapy or improved only slightly (> 2 wet nights per week). The mean duration of
therapy was 28 weeks, the mean dose of desmopressin was 30 microg and the median
follow-up 18 months. There were no significant side-effects. CONCLUSION: This
study indicates that rapid titration until dryness within 1-3 days, a long
maintenance therapy of at least 4-6 weeks and a slow stepwise reduction of dose
decreases the frequency of relapse and improves the outcome.
PMID- 9634015
TI - Combination therapy in the treatment of persistent nocturnal enuresis.
AB - OBJECTIVE: To evaluate, in a retrospective study, the response rate of older
children to combination therapy using a sustained-release anticholinergic agent,
hyoscyamine, and a synthetic analogue of antidiuretic hormone, desmopressin
acetate. PATIENTS AND METHOD: Twenty-eight patients (20 males and eight females,
aged 9-18 years) diagnosed with nocturnal enuresis were evaluated using a
questionnaire, history and physical examination. None had success with single
agent pharmacological therapy. All were begun on 0.375 mg of hyoscyamine and 20
microg of desmopressin intranasally at bedtime. The response rate was monitored
at 2 and 4 weeks, and then every 3 months by recording dry nights on a calendar.
To improve efficacy, the dosage of medication was adjusted up to 0.750 mg of
hyoscyamine and 60 microg of desmopressin. Upon achieving dryness and spontaneous
awakening to void, medication doses were tapered. RESULTS: Within 6 months 16
(57%) patients were completely dry and six (21%) were dry at least 80% of nights.
Nine patients relapsed during dose tapering and therapy was reinstituted.
Presently, 17 (60%) patients are off medication (after a mean of 8 months of
medication). Eight patients are still on medication and are dry at least 80% of
nights. Combination therapy failed in three patients and they have transferred to
a different regimen. None experienced untoward side-effects from the medications.
CONCLUSION: Most older children with nocturnal enuresis responded to combination
therapy. These children require long-term follow-up and may need medication for
up to 6 months because the relapse rate is fairly high. Combination therapy
appears safe and reliable in treating nocturnal enuresis in older children who
have had no success with other treatment modalities.
PMID- 9634016
TI - The effectiveness of desmopressin in the treatment of childhood nocturnal
enuresis: predicting response using pretreatment variables.
AB - OBJECTIVE: To determine the factors that predict the effectiveness of
desmopressin in the treatment of childhood nocturnal enuresis. PATIENTS AND
METHOD: Sixty-six children with monosymptomatic nocturnal enuresis were treated
with intranasal or oral desmopressin for a 4-week period. starting with a
standard dose of 20 microg (0.2 mg oral) and increasing after 2 weeks where no
progress was apparent to 40 microg (0.4 mg oral). Before treatment a range of
variables (demographic, situational, enuretic history, physiological, parental
attitude and child) were recorded. Three parameters of success acted as dependent
variables, with stepwise linear regression models used to determine pretreatment
predictors of success with desmopressin. RESULT: Each outcome variable produced a
very similar model of predictors. Success, as assessed by the most dry nights
over a 14-night period, was associated with less severe enuresis before
treatment, a parental belief that the child's enuresis was unstable and higher
birthweight. CONCLUSION: From the analysis, a model of arginine vasopressin
release is proposed and the clinical implications of the findings addressed.
PMID- 9634017
TI - Molecular genetic, clinical and psychiatric associations in nocturnal enuresis.
PMID- 9634018
TI - Persistent enuresis caused by nocturnal polyuria is a maturation defect of the
nyctihemeral rhythm of diuresis.
PMID- 9634019
TI - Monosymptomatic primary enuresis: differences between patients responding or not
responding to oral desmopressin.
AB - OBJECTIVES: To evaluate the 24-h diuresis, urinary osmolality, plasma arginine
vasopressin (AVP) and urinary prostaglandin E2 (PGE2) before and during
desmopressin treatment in patients with monosymptomatic primary enuresis (MPE),
and to investigate the possible depressor effect of desmopressin on the detrusor
in such patients with urodynamically confirmed bladder instability. PATIENTS AND
METHODS: Seven healthy children (control group) and 11 consecutive patients with
MPE (mean age 10.4 years, range 7-15) were assessed using laboratory tests, renal
and bladder ultrasonography, and video-urodynamic investigations. A 24-h
inpatient assessment with a controlled water intake of 20 mL/kg per day included
determinations of diuresis, urinary osmolality, AVP and PGE2 in both normal
children and those with MPE. After 30 days of treatment at optimal doses of
desmopressin, all children were hospitalized and re-evaluated during desmopressin
treatment; all completed 3 months of treatment at optimal doses. At the end of
this period, patients whose symptoms improved by > or = 80% were defined as
'responders' while those in whom they did not were defined as 'non-responders'.
RESULTS: After treatment, six of the 11 patients with MPE were 'responders' and
five 'non-responders'. Urodynamic evaluation showed bladder instability in seven
of the 11 patients with MPE but in those with bladder dysfunction, urodynamic
studies carried out during desmopressin treatment showed no changes in detrusor
activity. There were significant differences in the morning values of AVP between
normal children and responders (P < 0.03), and between responders and non
responders (P < 0.02); none of the non-responders had AVP levels of < 2.5 pg/mL,
while none of the responders exceeded this value. At midnight, responders had the
lowest mean AVP and non-responders the highest; this correlated with the highest
PGE2 value in the nonresponders at 00.00-08.00 hours. Non-responders had an
overnight mean PGE2 level greater than that in normal subjects or responders.
CONCLUSIONS: Polyuria occurred in all patients with MPE, independently of the
response to desmopressin. Responders had the lowest AVP values over the 24 h; the
morning AVP levels differentiated normal subjects from enuretic patients and
responders from non-responders. In patients with MPE, clinically undetected
bladder instability was unrelated to the results of treatment and there were no
urodynamic changes during desmopressin treatment. The differences between
enuretic patients suggested a different aetiology of MPE, probably related to an
increase in PGE2 concentration and an antagonistic mechanism of action of AVP or
desmopressin.
PMID- 9634020
TI - Primary enuresis: a urodynamic evaluation.
AB - OBJECTIVE: To assess urodynamic and clinical data in patients with primary
enuresis for potential prognostic indicators of detrusor instability. PATIENTS
AND METHODS: The records of 33 patients (mean age 8.8 years, range 5-14) with
monosymptomatic primary enuresis (MPE, bedwetting as the sole symptom) and 47
patients (mean age 7.1 years, range 5-12) with complicated primary enuresis (CPE,
bedwetting associated with diurnal urinary loss, squatting and urge incontinence)
were reviewed. The children underwent urodynamic studies to detect detrusor
instability and the prevalence was compared with the type of enuresis. RESULTS:
Of 33 patients with MPE, 17 (49%) showed either typical unstable detrusor
contractions (16) or low-compliance bladders (one); in the remaining 16 patients,
filling cystometry was normal and micturition was normal in all. Of the 47
patients with CPE, 35 (79%) showed detrusor instability and two decreased bladder
compliance; the remaining 10 had stable bladders and micturition was also normal
in all patients. CONCLUSION: The type of primary enuresis and the maximum
cystometric bladder capacity were good indicators of bladder dysfunction.
PMID- 9634021
TI - Evaluation of antidiuretic hormone before and after long-term treatment with
desmopressin in a group of enuretic children.
AB - OBJECTIVE: To determine the effect of long-term desmopressin therapy in enuretic
patients on the levels of antidiuretic hormone (ADH) during and after the end of
therapy. PATIENTS AND METHODS: The study comprised 25 outpatients (18 boys and
seven girls) aged 8-12 years at the start of therapy and 12-16 years at the end.
The morning (08.00 hours) plasma ADH level was determined before treatment (T0)
with desmopressin and 2 years after (T1) ending the therapy. Seven of the 25
patients evaluated had monosymptomatic (simple enuresis, SE) and 18 had other
symptoms (complex enuresis, CE). RESULTS: In the patients with SE, the mean (SD)
duration of therapy was 305 (183) days and they were reevaluated 2.5 (0.67) years
later. Of 18 patients with CE, eight were treated only with desmopressin for 204
(117) days. In 10 with an incomplete response after 30 days with only
desmopressin, oxybutynin (5 mg twice daily) was added; the duration of their
therapy was 255 (152) days and they were re-evaluated 3.9 (0.6) years later. The
mean (SD) ADH level in those with SE and CE was 2.14 (0.93) ng/L and 2.53 (1.16)
ng/L), respectively, both significantly lower (P < 0.001) than in controls, at
5.1 (1.6) ng/L. On re-evaluation at T1, there was a significant (P < 0.001)
increase in ADH levels over those at T0 in both groups, at 5.2 (0.8) and 5.3
(1.9) ng/L, respectively. CONCLUSION: These results seem to confirm the role
played by ADH in the pathophysiology of enuresis.
PMID- 9634022
TI - Parents' and young people's attitudes towards bedwetting and their influence on
behaviour, including readiness to engage in and persist with treatment.
PMID- 9634023
TI - Sleep and night-time behaviour of enuretics and non-enuretics.
AB - OBJECTIVE: To investigate connections between nocturnal enuresis and sleep
factors such as the subjective depth of sleep and classical parasomnias.
PATIENTS, SUBJECTS AND METHODS: One hundred school children aged 6-10 years
answered a questionnaire, with their parents, and the same questions were asked
of a group of 29 children of the same age suffering from severe nocturnal
enuresis. RESULTS: There were significant differences in arousability, with the
enuretic group being 'deep sleepers', and in the prevalence of onset insomnia,
nightmares, interrupted sleep and bedtime struggles, which were all less common
among the enuretics. The prevalence of classical parasomnias did not differ
between the groups. CONCLUSION: A high arousal threshold is one of the
pathogenetic factors underlying nocturnal enuresis and we propose that this group
of therapy-resistant enuretic children might not only sleep more deeply than
their nonenuretic peers, but perhaps have 'better' sleep.
PMID- 9634024
TI - Changes in the structure of sleep spindles and delta waves on
electroencephalography in patients with nocturnal enuresis.
AB - OBJECTIVE: To evaluate the mechanism of the dysfunction of arousal in patients
with Type I and Type IIa enuresis. PATIENTS AND METHODS: The numbers of sleep
spindles and delta waves were analysed during electroencephalography in 19
patients with enuresis (17 male, two female, mean age 9.7 years, range 8-14).
RESULTS: In four patients with Type I enuresis, who awoke spontaneously and
remained dry as a result of urinary sensation, the numbers of sleep spindles and
delta waves diminished gradually and finally disappeared just before the patients
awoke completely. In the remaining nine patients with Type I enuresis, there was
no decrease in the number of sleep spindles and delta waves, and enuresis
occurred without the subjects awakening. In the six patients with Type IIa
enuresis, there was no arousal reaction or generation of sleep spindles on
urination while asleep. CONCLUSIONS: An immaturity in the function of the
thalamus might be a cause of the arousal dysfunction in patients with Type I
enuresis. In Type IIa enuresis, a possible abnormal or immature arousal mechanism
in the pons or the lower tract may be responsible.
PMID- 9634025
TI - Continuous real-time ambulatory urodynamic monitoring in infants and young
children using infrared telemetry.
AB - OBJECTIVE: To assess the feasibility of continuous real-time ambulatory bladder
monitoring in infants and young children using a specially developed ambulatory
urodynamic data logger with built-in infrared telemetric on-line facilities.
PATIENTS AND METHODS: Twenty-nine infants and young children (mean age 3.9 years,
range 7 weeks to 9.5 years) with various types of bladder dysfunction underwent
urodynamic studies performed using an ambulatory urodynamic recorder with a
specially developed integral transmitter that converts digital pressure signals
to modulated infrared waves (935 nm). A receiver mounted on the ceiling of the
room receives the signals emitted from the recorder. During the investigation,
the infant can conduct normal activities, be totally mobile and be accompanied by
the mother undisturbed in a private cubicle. The urodynamicist in the next room
can observe all the patient's activities through a one-way mirror while
continuous real-time on-line pressure signal displays are recorded and monitored
using a computer, with event markers placed as necessary. For security, the data
recorded during ambulatory investigation are stored in the internal memory of the
ambulatory recorder. RESULTS: All 29 infants and young children completed the
urodynamic studies using the new system; the results were satisfactory and
reliable, with no data lost during ambulatory recording. The results obtained
using infrared telemetry were not significantly different from conventional
natural-filling urodynamic studies performed with a cabled on-line urodynamic
recorder. CONCLUSION: The infrared telemetry system provides a reliable and
effective way of performing continuous real-time ambulatory urodynamic monitoring
in infants and young children. With the development of more powerful telemetric
data transmission technologies, such a method could be extended in the near
future to a truly ambulatory urodynamic recording with real-time on-line
facilities, either at home or in the clinic, both for adults and for children.
PMID- 9634026
TI - Detrusor hypocontractility in children with posterior urethral valves arises
before puberty.
AB - OBJECTIVES: To assess prepubertal boys with posterior urethral valves (PUV) using
an analysis of pressure-flow studies to evaluate the voiding phase and thus
determine if myogenic failure (hypocontractility) arises before puberty and if it
can be detected early. PATIENTS AND METHODS: Eleven boys (8-13 years old) with
PUV underwent urodynamics and the results were analysed using pressure-flow
mathematical analysis (PFA) of the following variables of detrusor activity:
contraction velocity (Vdet), detrusor contractile power expressed as power factor
(WF) and Schafer's diagram, which differentiates a 'strong', 'normal' and 'weak'
detrusor. Vdet and WF were compared with normal values previously determined in
boys of similar age and considered 'low' if more than 2 SDs below the mean. The
results of PFA were compared with standard pressure-flow studies and the three
classical urodynamic patterns in boys with PUV, as determined by voiding
symptoms. The subsequent PFA of seven of the 11 boys were also assessed as they
had undergone previous urodynamics when < 8 years old. RESULTS: As assessed by
the three patterns of dysfunction, two boys had bladder instability, two had low
compliance and three had hypocontractility, with four boys being normal. From the
PFA, the Vdet and WF were lower than normal, respectively, in seven and nine of
the 11 boys; Schafer's nomogram showed a 'weak' detrusor in seven boys. The PFA
suggested a pathology in four of five boys with symptoms and in three of six with
no symptoms (two of the six showing a 'low' WF). Moreover, in older (11-13 years)
boys, all five had a 'weak' detrusor, a 'low' WF and four a 'low' Vdet. Of the
seven patients who underwent repeat PFA, three had a stable WF 3 years later, one
(normal) worsened slightly and two were clearly worse, while one, who underwent
late (at 3 years old) valve ablation, had an increased WF. CONCLUSIONS: The PFA
showed hypocontractility in two-thirds of prepubertal boys with PUV, including
asymptomatic patients. These findings confirm the hypothesis that bladder
dysfunction in boys with PUV eventually causes detrusor myogenic failure and
finally a postpubertal overdistended bladder.
PMID- 9634027
TI - An Italian epidemiological multicentre study of nocturnal enuresis.
AB - OBJECTIVE: To estimate the prevalence of enuresis in schoolchildren in Italy.
SUBJECTS AND METHODS: The Italian Club of Nocturnal Enuresis promoted a
prevalence study of nocturnal enuresis using a self-administered questionnaire in
seven cities in Northern, Central and Southern Italy. The association between
enuresis and potential risk factors, e.g. a family history of enuresis, stress,
socio-economic status and abnormal diurnal voiding habits, was investigated. The
perceived impact on the child and on the family was also evaluated. A random
cluster sampling scheme was used to obtain a sample of primary and secondary
schoolchildren from each city. One primary school and one secondary school for
each socio-economic level was sampled in each city, giving a total of 42 schools
surveyed; 9086 children were covered by the survey. In a cluster sampling method,
the variance of prevalence is divided into two components, binomial and extra
binomial variability. Both the DSM III and DSM IV definitions of enuresis were
used because at present, there is no consensus on the diagnostic criteria.
RESULTS: Completed questionnaires were received from 7012 children, an overall
response rate of 77.2%. Those aged 6-14 years were analysed, restricting the
sample to 6892 children. There were 250 enuretic children using the DSM III
definition of enuresis and 112 using the DSM IV definition. The overall
prevalence was 3.88% and showed a decreasing trend with increasing age.
Bedwetting was more frequent in boys than in girls. The prevalence of enuresis
was higher when the child was from a family of low socio-economic status despite
the child's age group. The logistic analysis showed that familiality, stress,
birthweight, age of attaining diurnal continence, soiling and, for girls,
menstruation, were statistically significant variables and thus contributed to
predicting the probability of bedwetting, confirming the findings of previous
studies. There was a large difference in prevalence using the two DSM
definitions; a high percentage of DSM III enuretic children had more than two wet
nights per week. CONCLUSION: It is important that a consensus about the 'working
definitions' of enuresis is reached to avoid bias in the recruitment step, to
carry out comparable epidemiological studies and to obtain adequate therapeutic
responses.
PMID- 9634028
TI - The natural history of urinary symptoms during adolescence.
AB - OBJECTIVE: To determine the prevalence and natural history of urinary symptoms
and incontinence among healthy adolescent schoolchildren. SUBJECTS AND METHODS: A
prospective longitudinal study using a confidential questionnaire administered to
an original cohort of 1176 local schoolchildren at 11-12 years and again at 15-16
years old. RESULTS: There was a decrease in the prevalence of urinary symptoms
with age. Daywetting was reported by 12.5% of children aged 11-12 years and 3.0%
of children aged 15-16 years. Nocturnal enuresis was reported by 4.7% of children
at 11-12 years and 1.1% at 15-16 years. Some of the children reporting daywetting
and nocturnal enuresis at 15-16 years old had not reported these symptoms at 11
12 years old. CONCLUSION: Urinary symptoms become less prevalent with age, but
are reported by a significant number of healthy schoolchildren.
PMID- 9634029
TI - A follow-up of enuresis from childhood to adolescence.
AB - OBJECTIVE: To determine the prevalence and treatment of enuresis in a national
population-based follow-up study of children aged 8-14 years, to evaluate
possible factors that enhance or hamper the attainment of continence and to
examine the relationships between enuresis and psychiatric disturbance. SUBJECTS
AND METHODS: An initial study was carried out in 1989 as part of the Finnish
Child Psychiatric National Epidemiological Study. Three types of questionnaires
were used; the Rutter Scale A for completion by parents, including a question
about enuresis, the Rutter scale B for completion by teachers and the Children's
Depression Inventory (CDI), completed by the children. Parents were also asked
about demographic and family issues, teachers about school achievements and
children about additional psychosomatic symptoms. In a follow-up in 1995, the
target population comprised all previous enuretics and their controls, matched by
age, gender, class and school, in the first phase of the study. Replies were
received from 315 enuretic boys and 186 girls, with the corresponding values for
controls being 310 and 183. The parents were asked about the adolescents' present
enuresis and for permission for a treatment trial, if needed. The adolescents
completed the CDI, and a questionnaire about enuresis, previous treatments and
possible willingness for a treatment trial. They also reported basic somatic
data, their life events and living habits. RESULTS: In the initial study, the
enuretic children had higher total and subscores as reported by parents, teachers
and themselves, except for emotional items reported by the teachers.
Additionally, a significantly greater proportion of these children soiled, had
sleeping difficulties and difficulties in falling asleep. Enuretic boys had more
frequent nightly arousal and early morning waking, while the enuretic girls had
more nightmares than non-enuretic girls. At 14 years old, the parents reported
that 13 adolescents were enuretic; from the children's replies, nine boys and
seven girls were enuretic. CONCLUSIONS: The prevalence of enuresis in those
previously enuretic was surprisingly low, probably because of the efficient
treatment methods, conditioning and medication. There were evident connections
between childhood enuresis and mental well-being.
PMID- 9634030
TI - Perceived stress of nocturnal enuresis in childhood.
PMID- 9634031
TI - Behavioural problems in children with urge incontinence and voiding postponement:
a comparison of a paediatric and child psychiatric sample.
AB - OBJECTIVE; To analyse prospectively the incidence of behavioural disorders and
the subjective views of children with urge incontinence (defined by detrusor
instability, sudden urge symptoms and frequent micturitions) and voiding
postponement (characterized by delayed micturition in typical situations and a
low voiding frequency) according to an identical protocol in a paediatric and a
child psychiatric unit. PATIENTS AND METHOD: Ninety-four consecutive or randomly
selected children aged 5.0-10.9 years with either voiding postponement (52) or
urge incontinence (42) were examined prospectively using an intelligence test
(CFT1 or CFT20), the Child Behaviour Checklist (CBCL 4/18), the ICD-10 child
psychiatric diagnoses and a structured interview. RESULTS: In the groups from
both centres combined, those postponing voiding had a significantly higher
incidence of externalizing behavioural symptoms (31% vs. 8%; P < 0.01) and total
problems (37% vs. 13%; P < 0.05) in the clinical range (CBCL), and a higher rate
of at least one ICD-10 child psychiatric diagnosis (54% vs. 29% P < 0.05) and of
expansive disorders (31% vs. 5%; P < 0.01). The incidence of children with
behavioural symptoms was lower in the paediatric centre, being exceptionally low
among urge incontinent children (only 6%, CBCL). In contrast, from the children's
subjective appraisal, there were no significant differences in concepts,
explanations and implications of wetting; 79% of urge incontinent children and
64% of those postponing voiding suffered emotionally from the adverse effects of
wetting. Only a minority (3% vs. 6%) saw any advantages at all. CONCLUSION:
Children with voiding postponement had a significantly higher incidence of
behavioural problems, especially expansive/externalizing behaviour, 3-4 times
higher than in the normal population. Children with urge incontinence had a
significantly lower incidence of behavioural problems, mainly emotional/
internalizing behaviour, that was only slightly higher (1-2 times) than that in
the normal population. Because of selection, similar trends but lower incidences
were found in the paediatric setting, with very few problems among urge
incontinent children. In contrast, the children's subjective views did not
differ; disadvantages associated with emotional suffering were reported by all
children.
PMID- 9634032
TI - The objective assessment of urinary incontinence in children.
AB - OBJECTIVE: To assess urinary incontinence objectively in children. PATIENTS AND
METHODS: Thirty-three children (mean age 8.2 years, range 5-12) were examined, of
whom 23 suffered from incontinence and 10 did not. The first method of assessing
incontinence was the 1-h pad-weighing test proposed by the International
Continence Society in 1983 and the second was a test in which the pad was weighed
between one urination and the next. At the end of the tests the volume of
normally voided urine was measured and the total voided volume during the test
calculated. The volume of urine lost during incontinence and the ratio
[incontinence volume/(incontinence volume + voided volume)] were evaluated; the
ratio was used because the bladder capacity in children differed with age.
RESULTS: In both tests, no wetting occurred in any of the 10 patients not
complaining of incontinence. In the 1-h pad-weighing test, no wetting occurred in
14 of the 23 patients complaining of incontinence but did in the nine remaining
patients, the loss being 1-30 g, and the incontinence ratio 0.5-14.8%. In the
second test, no wetting occurred in 12 of the 23 patients complaining of
incontinence but did so in the 11 remaining patients, with losses of 2-50 g and
incontinence ratios of 1.5-80.6%. CONCLUSIONS: There was no significant
difference between the tests in the incidence of incontinence. However, the
second method seemed to be more closely related to the clinical symptoms than was
the 1-h pad-weighing test and may be useful in the assessment of incontinence in
children.
PMID- 9634033
TI - Pelvic-floor therapy in girls with recurrent urinary tract infections and
dysfunctional voiding.
AB - OBJECTIVE: To analyse the treatment of girls with recurrent urinary tract
infections (UTIs, at least two periods confirmed) and urodynamically confirmed
dysfunctional voiding with pelvic-floor therapy. PATIENTS AND METHODS: Forty-two
girls with recurrent UTIs were treated prospectively during a study period of 18
months. Training consisted of an individually adapted voiding and drinking
schedule, pelvic-floor relaxation biofeedback, instructions on toilet behaviour
and biofeedback uroflowmetry; residual urine was estimated by ultrasonography.
All the girls received prophylactic antibiotics during treatment and those girls
with urodynamically proven detrusor instability (33) received anticholinergics.
Therapy was considered successful when the girls remained free of infection with
no further prophylactic antibiotics for at least 6 months. RESULTS: Four girls
younger than 6 years all suffered nocturnal and diurnal incontinence and two had
reflux. Treatment was effective for recurrent UTI in all and the reflux resolved
in two. All four girls became dry during the day and one became dry at night. In
the 38 girls older than 6 years, the treatment was successful for recurrent UTI
in 24 from the out-patient and in all three from the clinical programme. Reflux,
which was seen in six of these girls, resolved in five; one girl underwent
bilateral reimplantation. Incontinence was treated in all 23 girls with
incontinence problems before treatment (four of whom were initially dry). Twelve
girls needed a wetting alarm to become dry during the night. In four girls the
treatment was effective for recurrent UTI but the incontinence persisted; in
seven the treatment was considered unsuccessful as they all had UTIs after
treatment; all remained incontinent. Reflux persisted in all four girls in this
group who had reflux before treatment. CONCLUSION: The training programme was
effective in treating recurrent UTI in 35 of 42 girls (83%). The persistence of
incontinence problems is a bad prognostic factor for the recurrence of UTI after
the training programme. Pelvic-floor therapy seems a reasonable and meaningful
component in the treatment of recurrent UTIs in which detrusor-sphincter
dyssynergia plays a role.
PMID- 9634034
TI - Bladder autoaugmentation in myelodysplastic children.
AB - OBJECTIVE: To present the long-term results of bladder autoaugmentation in
myelodysplastic children with low compliance neurogenic bladders who failed
attempts at medical management, including clean intermittent catheterization
(CIC) and pharmacological bladder relaxation. PATIENTS AND METHODS: Twenty-one
patients with a neurogenic bladder after myelomeningocele operations (mean age
9.5 years, range 3-16) underwent autoaugmentation; 12 children were paraplegic
and hydrocephalic, and were treated by insertion of a ventriculoperitoneal valve.
All patients had low-compliance neurogenic bladders confirmed urodynamically. Ten
patients had vesico-ureteric reflux (VUR) and eight had dilated upper urinary
tracts with no reflux. All patients had been treated pre-operatively using CIC
and anticholinergic agents, with no success. RESULTS: Of 21 children treated
surgically, 17 were assessed urodynamically and examined to determine the
condition of the upper and lower urinary tract. The follow-up ranged from 3
months to 8 years (mean 6 years). In 13 patients the bladder capacity increased
by approximately 60 mL and in 14 the intravesical pressure decreased by
approximately 65 cmH2O. Fourteen children were continent using CIC (from 3- to 4
hourly); in the six patients with VUR the reflux resolved in two, decreased in
two and remained unchanged in two. Of eight patients with dilated upper tracts
but no reflux, seven improved. There was no improvement in bladder capacity in
four patients and no reduction in intravesical pressure in three. Two patients
underwent enterocystoplasty (one ileocystoplasty and one colocystoplasty) with
good results. Two children needed anticholinergic agents after autoaugmentation.
CONCLUSIONS: Autoaugmentation effectively reduces high intravesical pressure and
provides a sufficient increase in bladder capacity with a concomitant improvement
in urodynamic values. The present method allows the extent of the surgical
procedure to be limited to the extraperitoneal space and thus maintains all of
other options. Bladder autoaugmentation is a reasonable alternative to
enterocystoplasty in selected patients.
PMID- 9634035
TI - Colorectal dysfunction and faecal incontinence in children with spina bifida.
AB - OBJECTIVES: To quantify colorectal neurogenic dysfunction in children with spina
bifida and to evaluate the clinical efficacy of appropriate rehabilitation
performed by the coloproctologist in the spina bifida team. PATIENTS AND METHODS:
The bowel function of 73 patients with congenital (67) and acquired (six) spinal
lesions (age 7-25 years) was evaluated by one physician. Evacuation habit was
classified as full bowel control, mild and severe constipation or incontinence.
Fifty-two children had mild or severe incontinence or constipation, 22 of whom
were treated by the coloproctologist using biofeedback or conventional therapy;
30 were not treated. The outcome was compared between the groups RESULTS: Bowel
constipation remained stable in 90% and was complicated in 10% of the untreated
patients, while it ameliorated in 59% of patients who received specialist
treatment. CONCLUSION: Neurogenic bowel dysfunction needs specialist management
to achieve better results, using the concept of controlled incontinence. There
was no significant difference between conventional therapy and biofeedback
methods.
PMID- 9634036
TI - Using multimedia for patient information--a program about nocturnal enuresis.
AB - OBJECTIVES: To identify the information needs of children with nocturnal
enuresis, and to design, produce and evaluate an interactive computer program to
provide this information. SUBJECTS AND METHODS: The program was developed over an
18-month period using information provided by children, parents and
professionals, and was evaluated in a hospital-based enuresis clinic in 65
children. Usability and knowledge gained were also evaluated in 43 healthy
children aged 8-10 years attending a local inner-city primary school. RESULTS: An
interactive program about nocturnal enuresis was developed, which runs on a
personal computer and uses sound, voice, cartoon drawings and animation in a
modular design. Knowledge scores increased in clinic attendees and in
schoolchildren after using the program (Wilcoxon matched pairs test, P < 0.001).
This improvement was maintained when the program was re-tested 6-10 months later.
CONCLUSION: This interactive computer program holds children's attention and
increases their understanding of enuresis. Interactive multimedia may be useful
to complement the information provided by health professionals. This method of
communication may be particularly useful for children with a low level of
literacy.
PMID- 9634037
TI - The value of family screening for patients with cystine stone disease in northern
Jordan.
AB - OBJECTIVE: To assess the prevalence of cystinuria and cystine stone disease among
families of patients with cystine stones, and to determine their distribution by
age, sex and associated morbidity. SUBJECTS AND METHODS: The study comprised 180
relatives (87 males and 93 females, mean age 43 years) descended from two
brothers over four generations who live in two areas in northern Jordan. Data
were collected using a questionnaire and home visits, by urinary cystine testing
and radiology to detect stone, and assessing hypertension and renal impairment.
RESULTS: Of the 180 subjects, 104 (58%) had a positive reaction for cystine in
urine; 33 (32%) of these were younger than 15 years. Twenty members (11%) of the
families had evidence of renal cystine stone disease. Hypertension and renal
impairment were detected in a significant proportion of individuals with cystine
stone disease. CONCLUSION: Cystinuria is a major risk factor for cystine stone
formation. Family screening is valuable in detecting the cystinuric population
and in assessing individuals with stones. Early recognition, treatment and
counselling result in better management and prevention. The establishment of a
cystine study group in our region is essential.
PMID- 9634038
TI - Gene expression of prothrombin in the human kidney and its potential relevance to
kidney stone disease.
AB - OBJECTIVE: To determine whether urinary prothrombin fragment 1 (UPTF1), which
shows considerable promise as a critical determinant of calcium oxalate (CaOx)
stone formation, is manufactured by the human kidney. MATERIALS AND METHODS:
Ribonucleic acid was isolated from eight kidneys, two spleens and one liver.
Using reverse transcriptase-polymerase chain reaction, mRNA corresponding to the
UPTF1 portion of prothrombin was analysed by agarose-gel electrophoresis and
Southern blotting. RESULTS: Six kidney specimens showed clear evidence of
prothrombin gene expression; expression in the kidney was less than that in the
liver. CONCLUSION: This is the first demonstration of prothrombin gene expression
within the human kidney, a finding that not only has implications for CaOx stone
disease but also potentially for blood coagulation.
PMID- 9634039
TI - Nephroplication and nephropexy as an adjunct to primary surgery in the management
of giant hydronephrosis.
AB - OBJECTIVE: To study the role of nephroplication and nephropexy as an adjunct to
primary surgery in the management of giant hydronephrosis, with an aim to reduce
stasis and improve drainage, thus preventing consequent complications. PATIENTS
AND METHODS: Adjunctive nephroplication and nephropexy were performed in 20 renal
units of 16 patients with giant hydronephrosis treated between January 1992 and
March 1997. Twelve patients had unilateral and four had bilateral pelvi-ureteric
junction obstruction. Four patients had elevated serum creatinine levels. All
patients were treated with definitive surgery for the underlying disease and an
adjunctive nephroplication and nephropexy was performed at the same time.
RESULTS: Eighteen of the 20 renal units with giant hydronephrosis showed an
improvement in function and drainage as well as in pelvicalyceal system
dilatation, while one remained unchanged and one deteriorated. None of the
patients developed renal stones or pyelonephritis. Of the four patients with
azotaemia, three showed definite improvement to normal levels while one
stabilized. CONCLUSIONS: Nephroplication and nephropexy of giant hydronephrotic
kidneys are useful adjunctive procedures to reduce pelvicalyceal system stasis
and to improve drainage, thereby preventing subsequent stone formation, infection
and deterioration in renal function.
PMID- 9634040
TI - Rigid ureteroscopy in pregnant women.
AB - OBJECTIVE: To report our experience with rigid ureteroscopy in pregnant women.
PATIENTS AND METHODS: Ten pregnant women (mean age 25 years, SD 4.5, range 22-33)
with ureteric stones were treated by ureteroscopy. The mean (SD, range) gestation
time was 24 (6.5, 19-33) weeks. A standard rigid ureteroscope of 11.5 F was used
in eight patients and 9.5 F in two. The procedure was carried out with no
ureteric dilatation in three patients and with easy dilatation in seven.
Fluoroscopy was not used before or during ureteroscopy in any case.
Ultrasonography was available throughout the procedures for constant renal and
obstetric monitoring. RESULTS: Mid and lower ureteric stones were extracted by
basket or forceps in three patients and had to be disintegrated by ultrasound in
two. Upper ureteric stones were displaced to the kidney, with placement of double
pigtail ureteric stents, in three patients who were subsequently treated after
delivery. Ureteric oedema was seen in one patient and the endoscopic findings
were normal in the remaining patient. There were no obstetric complications. Two
patients had a urinary tract infection and one complained of stent-induced
bladder irritation. CONCLUSIONS: Rigid ureteroscopy is a safe and reliable method
in the diagnosis and treatment of ureteric calculi during pregnancy. The
procedure can be performed with ultrasonographic monitoring and without using
fluoroscopy.
PMID- 9634041
TI - The relevance of parity to ureteric dilatation.
AB - OBJECTIVE: To assess whether the mild dilatation of the right ureter in women
that is sometimes seen on intravenous urography (IVU) represents persistent
dilatation after a previous pregnancy. PATIENTS AND METHODS: The intravenous
urograms of 71 men, 63 parous and 27 nulliparous women were evaluated
prospectively. The two groups of women were divided into those with and without a
confirmed history of urinary tract infection (UTI) as the indication for IVU.
producing five groups in all. Measurements were taken on both the 5-min and the
compressed or release films on each side. RESULTS: There were no significant
differences in ureteric diameters among the five groups for the uncompressed
right ureter (P=0.23), the left ureter uncompressed (P=0.32) or compressed
(P=0.87). For the compressed right ureter, the difference was significant, with
the diameters in the parous women with proven UTIs being larger than in the other
groups (P=0.043). CONCLUSION: There is a significant increase in the diameter of
the compressed right ureter in the group of parous women with a history of proven
UTI. Infection or parity alone do not produce this effect: the combination of the
two factors is required.
PMID- 9634042
TI - Evaluation of clinical staging before cystectomy in transitional cell bladder
carcinoma: a long-term follow-up of 276 consecutive patients.
AB - OBJECTIVE: To evaluate retrospectively the clinical staging in a consecutive
series of patients selected for cystectomy and to define its limitations with a
view to possible improvements. PATIENTS AND METHODS: From 1979 to 1988, 276
patients with newly detected or recurring transitional cell carcinoma (TCC) of
the bladder, were offered pre-operative irradiation (20 Gy) and cystectomy. The
patients were assessed during 1995 and the outcome related to both clinical and
surgical data. Survival was analysed on the basis of 'intention to treat'.
Estimates of survival probabilities were calculated by the method of Kaplan and
Meier. Differences in survival among subgroups were assessed using the log rank
test and Cox stepwise regression analysis. RESULTS: Cancer-specific actuarial
survival for the whole series was 68% at 5 years and 63% at 10 years. Survival
was closely related to the depth of invasion found at surgery, clearly
discriminating those with tumours confined to the bladder wall (< or = P3A) from
those with extravesical extension (> or = P3B). The cancer-specific survival at 5
years for patients with < or = P3A tumours was 85% and for those with > or = P3B
tumours was 50%. This important distinction was anticipated accurately using
bimanual palpation before surgery, those patients with no palpable mass after
transurethral resection of bladder tumour (TURBT) having an actuarial survival of
83%, and those with a residual mass a survival of 50% at 5 years. In the
multivariate analysis, increasing clinical stage was the only pretreatment
variable with significant prognostic value for survival. However, this variable
was highly dependent on the palpatory findings after TURBT, the presence of a
residual mass being a prerequisite for the clinical stage T3 in case of muscle
invasive tumour. CONCLUSION: Bimanual palpation remains crucially important in
clinical staging, and there is a need for further standardization and refinement
of this procedure.
PMID- 9634043
TI - The early clinical course of primary Ta and T1 bladder cancer: a proposed
prognostic index.
AB - OBJECTIVE: To develop a simple prognostic index for anticipating more precisely
the early clinical course of primary superficial bladder cancer. PATIENTS AND
METHODS: The prognostic value of patient and tumour characteristics was examined
in 333 patients with primary Ta or T1 bladder cancer who participated in a
multicentre prospective study already completed. Primary tumour multiplicity, a
diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of
earlier recurrence in a multivariate analysis. A simplified prognostic index
consisted of the number of adverse tumour characteristics (ATCs) initially
present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free
of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and
69%, respectively, and none experienced progression. Recurrence outcomes
deteriorated consistently as the number of ATCs increased among the other three
groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free
probability was as low as 30% and 19%, and recurrence and tumour rates were about
2.6 times higher than in patients free of ATCs; 7% of these patients experienced
progression within 35 months of follow-up. CONCLUSION: A prognostic index based
on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1,
and grade 2 or 3) is a strong indicator of the clinical course of superficial
bladder cancer within 3 years of the first endoscopic resection. This proposal is
suggested for discussion and for validation in future studies but if confirmed,
this simple prognostic index may greatly help to identify indicators for adjuvant
intravesical therapy and to determine the optimal periodicity of control
cystoscopy regimens.
PMID- 9634044
TI - An evaluation of quality of life in patients with continent urinary diversions
after cystectomy.
AB - OBJECTIVE: To determine the long-term results and assess the quality of life in
patients with continent urinary diversions after cystectomy. PATIENTS AND
METHODS: Eighty-six consecutive patients who received a continent urinary
diversion from 1988 to 1994 at the Vancouver Hospital and Health Sciences Center
were evaluated. The evaluation comprised a review of their hospital charts and
clinic visits at 3 months and then yearly. Quality of life issues were assessed
using a postal questionnaire pertaining to the patient's urinary symptoms.
activity level and overall well-being while living with a continent urinary
diversion. Two separate questionnaires were sent, addressing heterotopic or
orthotopic diversions. RESULTS: There was an acceptable rate of complications,
with stone formation and urinary tract infection as the most common morbidities.
Continence was rated as good in most patients, with no patient reporting complete
incontinence. Undesirable urinary symptoms occurred less often than 20% of the
time in most patients. Although there was a significant effect on sex life, the
overall quality of life appeared to be very good, as 70% of the patients had no
limitations to their activities. CONCLUSIONS: The techniques currently evolved
for urinary diversion produce good long-term results and quality of life. These
diversions should be considered in a well selected patient population.
PMID- 9634045
TI - The impact of a modified ileal neobladder on the lifestyle and voiding patterns
in Asian patients.
AB - OBJECTIVE: To evaluate the impact of the modified ileal neobladder reconstruction
on lifestyle, voiding habits and functional outcome in Asian patients. PATIENTS
AND METHODS: Twenty-seven Asian patients (25 men and two women, mean age 59
years, range 41-76) underwent modified ileal neobladder reconstruction after
radical cystectomy for carcinoma of the bladder. The mean (range) follow-up was
21 (3-75) months. All patients were evaluated retrospectively using case notes,
reviews, interviews and voiding charts; 18 patients underwent urodynamic studies.
RESULT: Twenty-five patients (93%) achieved diurnal and 23 (85%) nocturnal
continence within 6 months. Of the 19 patients who were in employment before
surgery, 15 continued to be economically active afterward; 26 patients (96%)
reported no change in their daily living activities. Of 16 men who reported being
potent pre-operatively only four retained some residual erectile function. Twenty
three patients were interviewed about their voiding habits and satisfaction with
the outcome of surgery. Fourteen patients had no sensation of reservoir fullness
and of the 21 men, 13 had to squat or sit to void effectively. The mean (range)
voiding frequency was 5 (4-8) during the day and 2 (0-4) during sleep. Twenty-two
patients were satisfied with the overall outcome. CONCLUSIONS: The modified ileal
bladder provides a high urinary continence rate with minimal changes in daily
living activities and occupational status. The functional outcome was very
satisfactory and accepted well, despite some changes in reservoir sensation,
voiding posture and erectile function. The method is a viable option for
reconstruction after cystectomy in Asian patients.
PMID- 9634046
TI - The accuracy of the frequency-volume chart: comparison of self-reported and
measured volumes.
AB - OBJECTIVE: To assess the accuracy of frequency-volume charts recorded by patients
with voiding symptoms by comparing self-reported voiding data with the volumes of
urine collected in same period. PATIENTS AND METHODS: The study comprised 18
patients (median age 63 years, range 20-80) and lasted 3 days, during which the
patients recorded their fluid intake and voided volumes, and collected 24 h urine
samples. RESULTS: The recorded volumes exceeded or underestimated the collected
volume in 49% and 51%, respectively, of the samples, but the agreement between
the accumulated daily voiding volumes on the charts and the volumes collected was
acceptable. The median difference between volumes recorded on the charts and
collected as samples was 100 (0-1450) mL per 24 h or 10 (0-117) mL per voiding
(not significant). The median daily variation of creatinine in the urine was 1.1
(0.1-9.4) mmol (not significant), indicating that the 24 h collection periods
were respected. CONCLUSION: Recordings on frequency-volume charts are valid and
useful in the investigation of patients with voiding symptoms.
PMID- 9634047
TI - The management of men with acute urinary retention. National Prostatectomy Audit
Steering Group.
AB - OBJECTIVES: To determine the outcome of men with acute urinary retention
undergoing prostatectomy and to assess whether discharge with a catheter before
subsequent planned re-admission for prostatectomy had an adverse effect on
outcome. PATIENTS AND METHODS: A prospective cohort study was conducted of all
men undergoing prostatectomy in five health care regions over a 6-month period in
56 hospitals where prostatectomies were performed under the care of 103 surgeons.
The study included 3966 men undergoing prostatectomy, of whom 1242 presented with
acute urinary retention; the complication rates and symptomatic outcome were
assessed. RESULTS: Compared with those who underwent elective prostatectomy for
symptoms alone, men presenting with acute retention had an excess risk of death
at 30 days (relative risk [RR], 26.6, 95% confidence interval [CI], 3.5-204.5)
and at 90 days after operation (RR 4.4, 95% CI 2.5-7.6), and an increased risk of
perioperative complications. Although men with retention were older, had larger
glands and had more comorbidity, these factors did not totally explain the excess
risk. The final symptomatic outcome of men with acute retention was no different
from that of men presenting for elective treatment. Men with retention who were
managed by initial catheterization, sent home and subsequently re-admitted for
planned operation had similar pretreatment characteristics, post-operative
complications and outcomes to those who were kept in hospital throughout,
although the men kept in hospital had a total increased length of stay.
CONCLUSIONS: Men with acute retention have a high risk of developing
complications after undergoing prostatectomy. We were unable to confirm that a
short-term period of catheter drainage at home before re-admission for planned
surgery carried increased risks of peri-operative complications.
PMID- 9634048
TI - Transurethral electrovaporization of the prostate--a possible alternative to
transurethral resection: a one-year follow-up of a prospective randomized trial.
AB - OBJECTIVE: To compare the efficacy, safety and durability of transurethral
electrovaporization of the prostate (TUVP) with standard transurethral resection
(TURP) in a prospective randomized trial. PATIENTS AND METHODS: The study
included 104 consecutive men with symptomatic benign prostatic hyperplasia (BPH)
admitted for surgery who were randomized to TUVP or TURP. The variables evaluated
included the duration of surgery, catheterization and hospital stay, the
International Prostate Symptom Score (IPSS), a quality-of-life assessment (QOL),
the maximum urinary flow rate (Qmax) and the postvoid residual urine volume
(PVR). RESULTS: Both groups showed a comparable significant and maintained
decline in the mean IPSS, from 26.5 to 4.4 (TUVP) and from 26.6 to 5.9 (TURP),
and increase in mean Qmax, from 8.6 to 20.8 mL/s [corrected] (TUVP) and 8.6 to
22.8 mL/s (TURP) after 1 year. However, there were significant differences in the
mean duration of catheterization (TUVP 20.9 h, TURP 46.6 h, P<0.001), hospital
stay (TUVP 2.2 day, TURP 3.1 days, P<0.001), and the duration and volume of post
operative irrigation (TUVP none, TURP 18.1 h with 17.5 L of saline). Two patients
in each group developed urethral strictures (4%) and two patients in each group
required re-operation for residual adenoma (4%); two patients undergoing TURP had
a bladder neck stricture (4%). CONCLUSION: The results suggest that TUVP is as
effective as standard TURP in the treatment of moderate-sized BPH. TUVP offers
the advantage of using established instruments, has excellent peri-operative
haemostasis and requires a shorter hospital stay.
PMID- 9634049
TI - Interstitial radiofrequency therapy of the prostate in the management of acute
urinary retention.
AB - OBJECTIVE: To evaluate in a prospective study the efficacy of interstitial
radiofrequency therapy (IRFT) of the prostate in relieving acute urinary
retention in patients with benign prostatic hyperplasia. PATIENTS AND METHODS:
Twenty-seven patients presenting in acute urinary retention who failed at least
one trial of voiding one week after presentation were treated with IRFT of the
prostate. During the 6-month follow-up, the International Prostate Symptom Score
(IPSS), urinary flow rate, post-void residual volume (PVR) and serum creatinine
were determined and changes in erectile and ejaculatory functions recorded. The
treatment was considered successful if the patient resumed normal voiding,
without compromising renal function and without troublesome lower urinary tract
symptoms necessitating further treatment. RESULTS: Of the 26 evaluable patients,
77% resumed normal voiding. At 6 months after treatment, the mean (SD) IPSS had
decreased from 15.0 (8.3) to 8 (5.4), the PVR from 950 (203) to 88 (60) mL and
the maximum flow rate was 10.5 (4.36) mL/s. CONCLUSION: IRFT of the prostate is a
safe and effective treatment, at least in the short-term, for relieving acute
urinary retention in patients with benign prostatic hyperplasia. The longer term
follow-up is continuing.
PMID- 9634050
TI - Decreased incidence of prostate cancer with selenium supplementation: results of
a double-blind cancer prevention trial.
AB - OBJECTIVE: To test if supplemental dietary selenium is associated with changes in
the incidence of prostate cancer. PATIENTS AND METHOD: A total of 974 men with a
history of either a basal cell or squamous cell carcinoma were randomized to
either a daily supplement of 200 microg of selenium or a placebo. Patients were
treated for a mean of 4.5 years and followed for a mean of 6.5 years. RESULTS:
Selenium treatment was associated with a significant (63%) reduction in the
secondary endpoint of prostate cancer incidence during 1983-93. There were 13
prostate cancer cases in the selenium-treated group and 35 cases in the placebo
group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843
patients with initially normal levels of prostate-specific antigen (< or = 4
ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases
were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26
P=0.009). There were significant health benefits also for the other secondary
endpoints of total cancer mortality, and the incidence of total, lung and
colorectal cancer. There was no significant change in incidence for the primary
endpoints of basal and squamous cell carcinoma of the skin. In light of these
results, the 'blinded' phase of this trial was stopped early. CONCLUSIONS:
Although selenium shows no protective effects against the primary endpoint of
squamous and basal cell carcinomas of the skin, the selenium-treated group had
substantial reductions in the incidence of prostate cancer, and total cancer
incidence and mortality that demand further evaluation in well-controlled
prevention trials.
PMID- 9634051
TI - Urethroplasty for balanitis xerotica obliterans.
AB - OBJECTIVE: To review the results of different methods of urethroplasty for
anterior urethral strictures caused by balanitis xerotica obliterans (BXO).
PATIENTS AND METHODS: Twenty-eight patients underwent urethroplasty for BXO; 12
had a one-stage pedicled penile skin-flap urethroplasty and 16 excision and a two
stage free-graft urethroplasty using nongenital skin. RESULTS: The treatment
failed in all patients undergoing a one-stage pedicle penile skin urethroplasty
because the disease recurred with BXO, whereas the treatment failed in only one
patient using a two-stage free graft procedure. CONCLUSION: A two-stage free
graft urethroplasty using nongenital skin is recommended for anterior urethral
strictures caused by BXO.
PMID- 9634052
TI - Early experience with the use of buccal mucosa for substitution urethroplasty.
AB - OBJECTIVE: To evaluate the early results of anterior urethroplasty using a one
stage free graft with buccal mucosa. PATIENTS AND METHOD: Thirty-nine patients
(aged 23-59 years) underwent a one-stage urethroplasty using buccal mucosa, 28 as
a patch and 11 as tube grafts. All patients were evaluated by post-operative
urethrography at 6 months and were followed using urinary flow rates and symptoms
for 2-5 years. RESULT: There was one recurrent stricture (3%) in the group with a
patch urethroplasty but five of the 11 patients with tube grafts had a recurrent
stricture. CONCLUSION: The early results using buccal mucosa for patch
urethroplasty are encouraging. Although the results from tube grafts are poor,
they are similar to those from other methods of single-stage urethroplasty.
PMID- 9634053
TI - Managing many patients with a urethral stricture: a cost-benefit analysis of
treatment options.
AB - OBJECTIVES: To report a management method in a community where there are many
patients with urethral stricture and where the short-term goal of providing some
treatment to most may override the sometimes conflicting long-term aim of
minimizing recurrence rates. PATIENTS AND METHODS: Over a 3-year period, using
optical urethrotomy in 76 patients followed by intermittent self-dilatation (ISD)
in 29, urethroplasty in 28 and dilatation in three, 92 of 134 patients with a
urethral stricture were treated and the outcome compared. RESULTS: The overall
recurrence rate was 22%; a combination of urethrotomy plus ISD had a recurrence
rate of 17% and gave a mean duration of follow-up without recurrence similar to
that after urethroplasty. ISD significantly increased both the time before
recurrence and the duration of follow-up without recurrence after urethrotomy. In
addition to providing lasting treatment to many patients, urethrotomy was also 10
times cheaper, 10 times faster to perform and offered the surgeon better
protection from infection with human immunodeficiency virus than did
urethroplasty. CONCLUSION: Because wrongly selecting urethrotomy (resulting in a
failed procedure) wastes valuable operating time and resources, the pre-operative
recognition of strictures unsuitable for urethrotomy and their treatment by
urethroplasty is important for overall efficiency.
PMID- 9634054
TI - Histological changes associated with long-term urethral stents.
AB - OBJECTIVE: To assess the histological changes found in patients with long-term
external sphincter, prostatic and urethral stents. PATIENTS AND METHODS: Eighteen
patients with long-term stents (mean time since insertion 3.5 years) were
investigated. Three had external sphincter stents for detrusor-sphincter
dyssynergia secondary to spinal injury, eight had prostatic stents for
obstruction secondary to benign prostatic hyperplasia and seven had urethral
stents for recurrent strictures. Nine stents were occluded at investigation, of
which seven were entirely removed. The mucosae overlying the remaining two were
biopsied, as were mucosae over the nine patent stents, at urethroscopy. RESULTS:
The changes observed included polypoid hyperplasia (11 of 18 patients) between
and around the stent mesh wires, nonkeratinizing squamous metaplasia (two) or
hyperkeratotic squamous metaplasia (seven), chronic inflammation (15) with
prominent plasma cell infiltrates (11), variable foreign-body granuloma (two) and
microabscess formation (five), usually associated with clefts formed around the
stent wires (three of five). CONCLUSION: Stents become incorporated into the
urethral wall by a process of polypoid hyperplasia through the stent mesh, with
at least focal covering of the stent in most cases, and with variable
inflammatory infiltrates, most of which are rich in plasma cells. The urothelial
and connective tissue proliferation resulted in obstruction of the stent lumen in
nine of the patients studied. Further long-term study is necessary to exclude the
development of carcinoma in patients with keratinizing squamous metaplasia,
although no malignancy was seen in this study.
PMID- 9634055
TI - The outcome of varicocelectomy in subfertile men with an absent or atrophic right
testis.
AB - OBJECTIVES: To determine the effects of varicocelectomy on semen quality,
testicular volumes and serum hormone levels in subfertile men with an absent or
atrophic right testis. PATIENTS AND METHODS: Seventeen patients whose wives were
gynaecologically normal were evaluated with at least two semen analyses and
measurements of serum hormone levels and antisperm antibodies. Scrotal
ultrasonography was used to determine testicular volumes and spermatic vein
diameters. Varicocelectomy was performed by high ligation via an inguinal
approach. All patients were seen at a follow-up 3 months later, and after 6, 9
and 12 months the scrotal ultrasonography, hormone assessment and semen analyses
were repeated. Any pregnancies in their wives were recorded over a median follow
up of 19 months. RESULTS: After surgery, all patients had significant
improvements in sperm motility, morphology and concentration (P<0.01) but the
differences in pre- and post-operative testicular volumes and plasma hormone
levels were not statistically significant (P>0.01). No patients had immunological
infertility. Eleven of the wives became pregnant during the follow-up.
CONCLUSION: Higher pregnancy rates can be achieved by left varicocelectomy in
subfertile men with an absent or atrophic right testis. Sperm concentration,
motility and morphology are significantly improved by varicocelectomy.
PMID- 9634056
TI - Epididymectomy in the management of intrascrotal disease: a critical reappraisal.
AB - OBJECTIVE: To assess the outcome of epididymectomy as a method of treating
epididymal pathology. PATIENTS AND METHODS: Forty-one patients who underwent
epididymectomy between 1990 and 1995 were analysed retrospectively; their
clinical records were reviewed and their satisfaction with the outcome and relief
of symptoms assessed using a questionnaire and/or telephone interview. RESULTS:
Twenty-nine patients with pain were subdivided into three categories depending on
the indication for epididymectomy, i.e. post-vasectomy epididymal engorgement
(eight patients), complex cystic disease (11) or 'chronic epididymitis' (10). The
outcome was satisfactory in 27 of the 29 patients. The best results were obtained
in the group who underwent epididymectomy after vasectomy, where seven of eight
improved after the procedure. Those with chronic epididymitis had the least
favourable outcome, with only seven reporting any improvement in symptoms.
CONCLUSIONS: Epididymectomy has a valuable role in the management of epididymal
pathology in appropriately selected patients.
PMID- 9634057
TI - Endoscopic removal of a complex foreign body from the bladder.
PMID- 9634058
TI - Ureteroscopic retrieval of proximally displaced ureteric stents using triradiate
grasping forceps.
PMID- 9634059
TI - Benign teratoma of the urachus.
PMID- 9634060
TI - Exstrophic abdominal wall defect without bladder exstrophy (pseudo-exstrophy)
PMID- 9634061
TI - Urinary bladder rupture: laparoscopic repair.
PMID- 9634062
TI - Urinary incontinence: an unusual manifestation of a forgotten stent.
PMID- 9634063
TI - Retroperitoneal fibrosis: an unusual complication of intra-arterial stents and
angioplasty.
PMID- 9634064
TI - 'Stones, gas and gaiters': gas-filled matrix calculi of the renal pelvis.
PMID- 9634065
TI - Renal angiomyolipoma associated with inferior vena caval tumour thrombus.
PMID- 9634066
TI - A peculiar case of granulomatous prostatitis: a cause for concern.
PMID- 9634067
TI - Metastatic prostatic carcinoma in a male-to-female transsexual.
PMID- 9634068
TI - Spontaneous anticoagulant-induced testicular haemorrhage mimicking a testicular
tumour.
PMID- 9634069
TI - Safety and efficacy of transurethral needle ablation of the prostate for
symptomatic outlet obstruction.
PMID- 9634070
TI - Clinical review of 100 consecutive surgically treated patients with upper tract
transitional tumours.
PMID- 9634071
TI - The use of the bladder-tumour associated analyte test to determine the type of
cystoscopy in the follow-up of patients with bladder cancer.
PMID- 9634072
TI - Viral proteins that regulate cellular signalling.
PMID- 9634073
TI - Retrovirus mutation rates and their role in genetic variation.
PMID- 9634074
TI - A proline-to-histidine substitution at position 225 of human immunodeficiency
virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U
90152.
AB - Two mutant virus strains in which the novel P225H mutation appeared in a V106A
reverse transcriptase (RT)-mutated genetic background upon treatment of human
immunodeficiency virus type 1 (HIV-1) with quinoxaline S-2720 were isolated.
Surprisingly, the addition of the P225H mutation to the V106A RT mutant genetic
background resensitized the V106A RT mutant virus to the non-nucleoside RT
inhibitor (NNRTI) BHAP U-90152, but not to other NNRTIs. Construction of both
recombinant viruses and recombinant RTs containing the V106A, P225H and
V106A+P225H mutations revealed that P225H was indeed responsible for the marked
potentiation of the antiviral activity of BHAP against the P225H single-mutant
virus and the V106A+P225H double-mutant virus when compared to wild-type and
V106A single-mutant viruses, respectively. An explanation for the markedly
increased sensitivity of the P225H mutant HIV-1 RT to BHAP and not to the other
NNRTIs was provided by the unique features of the X-ray structure of the RT-BHAP
complex.
PMID- 9634075
TI - Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB
dependent activation of human immunodeficiency virus type 1 long terminal repeat
in T cells.
AB - Tuberculosis has emerged as an epidemic, extended by the large number of
individuals infected with human immunodeficiency virus type 1 (HIV-1). The major
goal of this study was to determine whether the mycobacterial cell wall component
mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M.
tuberculosis) could activate transcription of HIV-1 in T cells with the use of an
in vitro cell culture system. These experiments are of prime importance
considering that CD4-expressing T lymphocytes represent the major virus reservoir
in the peripheral blood of infected individuals. Using the 1G5 cell line
harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it
was first found that culture protein filtrates (CFP) from M. tuberculosis or
purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike
similarly prepared CFP extracts devoid of ManLAM. The implication of protein
tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by
the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene
expression using herbimycin A and H7. It was also determined, using
electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the
nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis
ManLAM resulted in clear induction of the luciferase gene placed under the
control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally,
the ManLAM-mediated activation of HIV-1 LTR transcription was found to be
independent of the autocrine or paracrine action of endogenous TNF-alpha. The
results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells
and could thus have the potential to influence the pathogenesis of HIV-1
infection.
PMID- 9634076
TI - Dependence on host cell cycle for activation of human immunodeficiency virus type
1 gene expression from latency.
AB - Human immunodeficiency virus type 1 (HIV-1) establishes latent infection of a
certain population of CD4+ host cells which could be long-term reservoirs for HIV
1. The expression of viral genes in such long-term infected cells is strongly
regulated by cellular status, such as the phase of the cell cycle or stage of
cell differentiation. Here, viral gene expression in synchronized U1 cells, a
monocytic cell clone latently infected with HIV-1, was characterized. The
expression of HIV-1 antigens was detected exclusively at G2/M phase in U1 cells,
irrespective of phorbol myristate acetate (PMA) treatment. The induction of HIV-1
gene expression in PMA-treated cells was due to the recruitment of NF-kappaB with
DNA-binding activity at G2/M phase. Activated NF-kappaB was induced only by PMA
treatment during the late G1 to S, but not after entering G2 phase, indicating
that the transcriptional factor(s) involved in viral gene expression is also
largely regulated by the host cell cycle. In contrast, the enhancement of antigen
expression by treatment with tumour necrosis factor-alpha (TNF-alpha) was cell
cycle-independent. In fact, NF-kappaB was activated 2 h after TNF-alpha treatment
at all stages of the cell cycle. Thus, the mechanisms of HIV-1 activation from
latency in U1 cells by PMA and TNF-alpha treatment are different. The model
system using U1 cells shown here may provide insight into the mechanisms
responsible for HIV-1 gene expression from latency.
PMID- 9634077
TI - Sequence analysis of the NS5A protein of European hepatitis C virus 1b isolates
and relation to interferon sensitivity.
AB - Japanese studies have defined the discrete 2209-2248 amino acid region of the non
structural 5A protein (NS5A(2209-2248)) of hepatitis C virus genotype 1b (HCV 1b)
isolates as the interferon sensitivity determining region (ISDR). European
studies did not confirm these results since most of the ISDR sequences harboured
an intermediate profile. Recently, a direct interaction between the NS5A protein,
involving the ISDR, and the interferon-induced protein kinase (PKR) has been
reported and presented as a possible explanation of HCV interferon resistance. In
the present study, the entire NS5A amino acid sequence from 11 resistant and
eight sensitive strains from European HCV 1b isolates was inferred from direct
sequencing. The previously described important amino acid stretches and positions
in NS5A were compared between the resistant and sensitive groups. Although some
variations were observed, no clear differences could be directly correlated with
the interferon sensitivity. However, sensitive strains were different, owing to
more amino acid changes when compared to a consensus sequence from all strains.
The carboxy-terminal region and especially the previously reported NS5A/V3 region
showed most of the variations. Moreover, the conformational analysis of NS5A by
secondary structure prediction allowed the differentiation of most sensitive
strains from resistant ones. It was concluded that other regions different from
ISDR were involved in resistance to interferon maybe via the interaction between
NS5A and PKR.
PMID- 9634078
TI - Infection of a chimpanzee with hepatitis C virus grown in cell culture.
AB - Culture supernatant harvested from Daudi cells, a lymphoplastoid cell line, after
58 days of infection with the H77 strain of hepatitis C virus (HCV), was
inoculated into a chimpanzee. HCV RNA, as detected by RT-PCR, first appeared in
the serum and liver 5 and 6 weeks, respectively, after inoculation. Peripheral
blood mononuclear cells (PBMC) collected on week 7 were also positive for HCV
RNA. The major sequences of hypervariable region 1 (HVR1) of the viral genome
recovered from the inoculated chimpanzee were the ones which were the majority in
the original H77 inoculum and not those which were in the majority in the culture
supernatant. Only the sequence recovered from PBMC was the same as the major one
found in the cell culture.
PMID- 9634079
TI - Characterization of determinants involved in the feline infectious peritonitis
virus receptor function of feline aminopeptidase N.
AB - Feline aminopeptidase N (fAPN) is a major cell surface receptor for feline
infectious peritonitis virus (FIPV), transmissible gastroenteritis virus (TGEV),
human coronavirus 229E (HCV 229E) and canine coronavirus (CCV). By using chimeric
molecules assembled from porcine, human and feline APN we have analysed the
determinants involved in the coronavirus receptor function of fAPN. Our results
show that amino acids 670-840 of fAPN are critically involved in its FIPV and
TGEV receptor function whereas amino acids 135-297 are essential for the HCV 229E
receptor function. We also demonstrate that a chimeric molecule assembled from
human and porcine APN is able to act as a receptor for FIPV. This is surprising
as neither human nor porcine APN by themselves mediate FIPV infection. These
results suggest that different determinants in the APN protein are involved in
mediating the coronavirus receptor function.
PMID- 9634080
TI - The ectodomains but not the transmembrane domains of the fusion proteins of
subtypes A and B avian pneumovirus are conserved to a similar extent as those of
human respiratory syncytial virus.
AB - The fusion glycoprotein (F(B)) gene of five strains of the B subtype of avian
pneumovirus (APV; turkey rhinotracheitis virus) has been sequenced. The length of
the F(B) protein was 538 amino acids, identical to that of the F protein of
subtype A virus, with which it had 74% and 83% overall nucleotide and deduced
amino acid identities, respectively. The F(B) and F(A) ectodomains had 90% amino
acid identity, very similar to the 91% identity between the ectodomains of the F
proteins of subtype A and B human respiratory syncytial virus (HRSV). As with
HRSV, the F2 polypeptide was less conserved (83% identity) than F1 (94%). In
contrast to the ectodomain, the transmembrane and cytoplasmic domains of the two
APV subtypes were much less conserved (30% and 48% identity, respectively) than
those of HRSV (92% and 87%, respectively). Comparisons within all the genera of
the Paramyxoviridae (Pneumovirus, Morbillivirus, Paramyxovirus and Rubullavirus)
show that low amino acid identity between F protein transmembrane domains is a
feature of different species of virus rather than of strain differences. This may
indicate that the two subtypes of APV have evolved in different geographical
regions and/or different avian species. This is the first report of an F gene
sequence from a subtype B APV.
PMID- 9634081
TI - Identification of regions of bovine respiratory syncytial virus N protein
required for binding to P protein and self-assembly.
AB - The interaction of bovine respiratory syncytial virus (BRSV) nucleocapsid protein
(N) with itself and phosphoprotein (P) was investigated using the yeast two
hybrid system. N-P interaction was abolished by any of a series of internal
deletions or deletions at the C terminus. In contrast, removal of up to 32 amino
acids from the N terminus had little effect. Interestingly, while removal of the
C-terminal 32 amino acids ablated interaction, it was largely restored by a
second deletion removing up to 32 amino acids from the N terminus. Many of these
interactions of the BRSV N protein demonstrated a pattern that was similar to
those occurring in the N protein of related viruses. N-N interaction was
abolished by any of the internal deletions; however, removal of up to 32 amino
acids from the N terminus or C terminus was tolerated and increased the strength
of the interaction between the two N proteins.
PMID- 9634082
TI - A host restriction-based selection system for influenza haemagglutinin
transfectant viruses.
AB - During the 1996 influenza epidemic in Vienna we obtained influenza A virus
specimens (Vienna/47/96, Vienna/81/96) which grow efficiently in African green
monkey kidney (Vero) cells but not in embryonated chicken eggs. Amplification of
the specimens in Vero cells resulted in progeny that agglutinated human but not
chicken erythrocytes. Reassortment analysis suggested that the haemagglutinin
(HA) might be responsible for the host restriction. Vero cells were infected with
the Vienna/47/96 virus and then transfected with reconstituted ribonucleoprotein
complexes containing HA genes from egg-adapted strains. Subsequent selective
passages in embryonated chicken eggs resulted in selection of transfectant
viruses, growing in eggs and containing the transfected HAs. The results
demonstrate that host restriction of the Vero-adapted Vienna/47/96 virus is due
to its HA. Moreover, the experiments showed that the Vienna/47/96 strain can be
used as helper virus for reverse genetics experiments.
PMID- 9634083
TI - Identification and characterization of RNA-binding activities of avian reovirus
non-structural protein sigmaNS.
AB - Cytoplasmic extracts prepared from avian reovirus (ARV) strain S1133-infected
chicken embryo fibroblasts were examined for the presence of RNA-binding proteins
in order to identify and characterize ARV RNA-binding proteins. Analysis of
binding activity to poly(A)-Sepharose indicated that infected cells contained
significant amounts of a protein that co-migrated with ARV protein sigmaNS
present in total virus-infected cell extracts. Determination of the N-terminal
amino acid sequence of several peptide fragments generated by V8 protease
digestion of the poly(A)-Sepharose-purified protein confirmed that this viral
protein was sigmaNS. Competition assays showed that single-stranded RNA from the
unrelated avian pathogen infectious bursal disease virus was able to compete for
binding of sigmaNS to poly(A)-Sepharose. These data suggest that ARV sigmaNS
binds to single-stranded RNA in a nucleotide sequence non-specific manner and is
functionally similar to its counterpart specified by mammalian reovirus.
PMID- 9634084
TI - Roles of vaccinia virus EEV-specific proteins in intracellular actin tail
formation and low pH-induced cell-cell fusion.
AB - During vaccinia virus (VV) morphogenesis intracellular mature virus (IMV) is
wrapped by two additional membranes to form intracellular enveloped virus (IEV).
IEV particles can nucleate the formation of actin tails which aid movement of
IEVs to the cell surface where the outer IEV membrane fuses with the plasma
membrane forming cell-associated enveloped virus (CEV) which remains attached to
the cell, or extracellular enveloped virus (EEV) which is shed from the cell. In
this report, we have used a collection of VV mutants lacking individual EEV
specific proteins to compare the roles of these proteins in the formation of IEV
and IEV-associated actin tails and fusion of infected cells after a low pH shock.
Data presented here show that p45-50 (A36R) is not required for IEV formation or
for acid-induced cell-cell fusion, but is required for formation of IEV
associated actin tails. In contrast, gp86 (A56R), the virus haemagglutinin, is
not required for formation of either IEV or IEV-associated actin tails. Data
presented also confirm that p37 (gene F13L), gp42 (B5R) and gp22-24 (A34R) are
needed for formation of IEV-associated actin tails and for cell-cell fusion after
low pH shock. The phenotypes of these mutants were not affected by the host cell
type as similar results were obtained in a range of different cells. Lastly,
comparisons of the phenotypes of VV strains Western Reserve, deltaA34R and
deltaA36R demonstrate that actin tails are not required for low pH-induced cell
cell fusion.
PMID- 9634085
TI - African swine fever: a disease characterized by apoptosis.
AB - The cell tropism, organ distribution and resultant pathology of African swine
fever were compared in domestic pigs infected with lethal (Malawi) and sublethal
(Malta) isolates of African swine fever virus (ASFV). After infections with both
isolates, ASFV was predominantly localized in cells of the mononuclear phagocytic
system and was not observed in endothelial cells in lymphoid tissue. More severe
tissue destruction and cell depletion, associated with high levels of infected
macrophages, were seen in lymphoid tissues from domestic pigs infected with the
virulent Malawi isolate compared to the less virulent Malta isolate of ASFV. The
abundant lymphocyte death was caused by apoptosis and not necrosis. In the
spleen, as early as 3 days post-infection (p.i.), many lymphocytes in the B and T
cell areas of the white and red pulp were apoptotic. Apoptosis in the T cells of
the periarteriolar lymphoid sheaths in the spleen, however, occurred later, at 5
7 days p.i. In lymph nodes apoptosis was observed in T lymphocytes as early as 4
days p.i. and extended to B lymphocytes in the follicles later in infection. In
pigs recovered from infection with the sublethal Malta isolate, virus was found
to persist in lymph nodes and tonsils for up to 48 days p.i. and was located in
cells, surrounded by apoptotic lymphocytes, in the paracortex of lymph nodes up
to 32 days p.i. Taken together, these observations suggest that apoptosis of
uninfected lymphocytes was induced by cytokines or apoptotic mediators released
from ASFV infected macrophages.
PMID- 9634086
TI - The pathogenesis of African swine fever in the resistant bushpig.
AB - Bushpigs and warthogs are natural reservoir hosts of African swine fever virus
(ASFV) in the wild, showing no clinical signs of disease when infected with the
same highly virulent isolates of ASFV that induce rapid, haemorrhagic death in
domestic pigs. In contrast to domestic pigs, infection of bushpigs with Malawi
isolate results in low levels of virus replication and lymphocyte apoptosis
within the spleen, and a relatively low spread of virus to other lymphoid
tissues. However, at 10 days post-infection, a high degree of apoptosis was seen
in B lymphocytes of the B cell follicles in bushpig lymph nodes. Virus infected
cells were present amongst the apoptotic B cells of these follicles, suggesting
that indirect factors released from ASFV infected macrophages signal surrounding
lymphocytes to enter apoptosis. The susceptibility/resistance of domestic
pigs/bushpigs to ASFV may serve as a unique veterinary model for the recently
emerging haemorrhagic disease of man.
PMID- 9634087
TI - Restricted expression of Epstein-Barr virus (EBV)-encoded, growth transformation
associated antigens in an EBV- and human herpesvirus type 8-carrying body cavity
lymphoma line.
AB - A body cavity lymphoma-derived cell line (BC1), known to carry both Epstein-Barr
virus (EBV) and human herpes virus type 8 (HHV-8; or Kaposi's sarcoma-associated
herpesvirus, KSHV), was analysed for the expression of EBV-encoded, growth
transformation-associated antigens and cellular phenotype by immunofluorescence
staining, Western blotting, RT-PCR and flow cytometry. A similar phenotypic
analysis was also performed on another body cavity lymphoma line, BCBL1, that is
singly infected with HHV-8. Phenotypically, the two lines were closely similar.
Although both lines are known to carry rearranged immunoglobulin genes, they were
mostly negative for B-cell surface markers. Both expressed the HHV-8-encoded
nuclear antigen (LNA1). Similarly to Epstein-Barr nuclear antigen type 1 (EBNA1),
LNA1 was associated with the chromatin in interphase nuclei and the mitotic
chromosomes in metaphase. It accumulated in a few well-circumscribed nuclear
bodies that did not co-localize with EBNA1. BC1 cells expressed EBNA1, LMP2A and
EBV-encoded small RNAs but not EBNA2-6, LMP1 and LMP2B. They were thus similar to
type I Burkitt's lymphoma cells and latently infected peripheral B-cells.
Analysis of the splicing pattern of the EBNA1-encoding message by RT-PCR showed
that BC1 cells used the QUK but not the YUK splice, indicating that the mRNA was
initiated from Qp and not from Cp or Wp.
PMID- 9634088
TI - Analysis of the hexon gene sequence of bovine adenovirus type 4 provides further
support for a new adenovirus genus (Atadenovirus).
AB - The putative hexon gene of bovine adenovirus type 4 (BAV-4), encoding 910 amino
acid residues, has been identified and sequenced. A characteristic codon usage
biased towards the use of AT-rich triplets was observed. Comparative analysis
with other hexon sequences detected a high level of amino acid identity in the
regions corresponding to the pedestals of the hexon. Substitutions, insertions
and deletions were identified mainly in the variable regions forming the loops
which are exposed on the outer surface of the virion. In these variable regions,
BAV-4 shared similarity only with egg drop syndrome (EDS) virus and ovine
adenovirus isolate 287 (OAV287). The close relationship of these viruses was also
demonstrated by phylogenetic analysis of the hexon gene. In addition to the two
groups of the Mastadenovirus and Aviadenovirus genera, a third cluster appeared
comprising BAV-4, OAV287 and EDS virus.
PMID- 9634089
TI - Complementation of a fibre mutant adenovirus by packaging cell lines stably
expressing the adenovirus type 5 fibre protein.
AB - Adenovirus-based gene therapy vectors now in use cannot be targeted to specific
cell types in vivo and are immunogenic, properties which limit their clinical
utility. Improved vectors lacking the genes for viral structural proteins may
overcome these limitations. We have developed cell lines which stably express the
adenovirus type 5 (Ad5) fibre protein in its native trimeric form. These cells
can complement an Ad5 mutant with a defect in the fibre gene, and are capable of
incorporating the Ad5 fibre into particles of a different Ad serotype. As the
fibre protein is responsible for the initial binding of virus to cells, packaging
cell lines expressing different or modified fibre proteins will be useful in
studying the mechanism by which adenovirus infects different cell types.
PMID- 9634090
TI - MHC class I molecules are enriched in caveolae but do not enter with simian virus
40.
AB - Simian virus 40 (SV40) binds to MHC class I molecules anywhere on the cell
surface and then enters through caveolae. The fate of class I molecules after
SV40 binding is not known. Sensitivity of 125I-surface-labelled class I molecules
to papain cleavage was used to distinguish internalized class I molecules from
class I molecules remaining at the cell surface. Whereas the caveolae-enriched
membrane microdomain was found to also be enriched for class I molecules, no
internalized papain-resistant 125I-surface-labelled class I molecules could be
detected at any time in either control cells or in cells preadsorbed with
saturating amounts of SV40. Instead, 125I-surface-labelled class I molecules, as
well as preadsorbed 125I-labelled anti-class I antibodies, accumulated in the
medium, coincident with the turnover of class I molecules at the cell surface.
The class I heavy chains that accumulated in the medium were truncated and their
release was specifically prevented by the metalloprotease inhibitor 1,10
phenanthroline. Thus, whereas class I molecules mediate SV40 binding, they do not
appear to mediate SV40 entry.
PMID- 9634091
TI - Taxonomic characteristics of fijiviruses based on nucleotide sequences of the oat
sterile dwarf virus genome.
AB - Sequence determination of full-length cDNA clones of genomic segments 7-10 (S7
S10) of oat sterile dwarf fijivirus (OSDV) revealed that the 5' and 3' ends of
the plus strands of these segments had the same conserved terminal sequences, 5'
AACGAAAAA and UUUUUUUAGUC 3'. These sequences are similar, but not identical, to
the conserved terminal nucleotide sequences of the genomic segments of rice black
streaked dwarf fijivirus (RBSDV) and maize rough dwarf fijivirus (MRDV). The
coding strands of S7 and S10 each contained two large nonoverlapping open reading
frames (ORFs), as do RBSDV S7 and S9, MRDV S6 and S8 and Nilaparvata lugens
reovirus (NLRV; a putative member of Fijivirus) S9. These results strongly
suggest that the dicistronic nature of certain genomic segments is characteristic
of fijiviruses. Computer analyses revealed sequence homology between RBSDV S7
ORF2, MRDV S6 ORF2 and OSDV S7 ORF2, suggesting that this protein is conserved
among plant fijiviruses. No counterparts were found in the genome of NLRV, which
is a nonphytopathogenic insect reovirus. Furthermore, phylogenetic trees derived
from multiple sequence alignments of each of the homologous proteins from OSDV,
RBSDV, MRDV and NLRV suggest that NLRV did not evolve from either Fijivirus group
2 (RBSDV and MRDV) or group 3 (OSDV).
PMID- 9634092
TI - Detection and assignment of proteins encoded by rice black streaked dwarf
fijivirus S7, S8, S9 and S10.
AB - The proteins encoded by rice black streaked dwarf fijivirus (RBSDV) genomic
segments 7-10 (S7-S10) were characterized. Open reading frames (ORFs) from these
segments were expressed as fusion proteins in Escherichia coli. Antibodies raised
against the expressed products were used as probes to determine whether the viral
ORFs encode structural proteins. In Western blots, antibodies to the expressed S8
and S10 products reacted with a core capsid (65 kDa) and a major outer capsid (56
kDa) protein, respectively, while none of the antibodies to S7 and S9 products
reacted with structural proteins. Antisera to RBSDV S7 ORF1 and S9 ORF1 each
detected a single protein of the predicted size in total protein extracts from
infected rice plants and viruliferous Laodelphax striatellus. Immunoelectron
microscopy revealed that antibodies to RBSDV S7 ORF1 and RBSDV S9 ORF1 reacted
with tubular structures and viroplasm, respectively, in sections of both infected
maize plants and viruliferous L. striatellus. Antisera to ORF2 of S7 and S9
failed to detect any proteins in the infected tissue using either Western
blotting or immuno-electron microscopic techniques.
PMID- 9634093
TI - Characterization of cis-acting elements affecting strength and phloem specificity
of the coconut foliar decay virus promoter.
AB - During replication in its host plant, coconut foliar decay virus (CFDV) remains
restricted to the phloem tissue. Previous in vivo studies on subgenomic CFDV DNA
had provided evidence for the phloem specificity of the CFDV promoter. Here, new
promoter constructs are described which are distinguished by the presence or
absence of various cis-acting signals and which gave rise to a 16-fold higher
reporter gene (beta-glucuronidase) activity (reaching 30% of the cauliflower
mosaic virus 35S promoter) in tobacco protoplasts, while the phloem specificity
in transgenic tobacco plants was conserved. Surprisingly, the CFDV stem-loop
structure dramatically influenced transcriptional efficiency. From these studies
and sequence comparisons with other phloem-specific promoters, cis-signals
involved in CFDV promoter strength and tissue specificity were identified.
PMID- 9634094
TI - Defective forms of cotton leaf curl virus DNA-A that have different combinations
of sequence deletion, duplication, inversion and rearrangement.
AB - Tobacco and tomato plants inoculated at least 9 months previously with a
Pakistani isolate of cotton leaf curl virus (CLCuV-PK), a whitefly-transmitted
geminivirus, contained substantial amounts of circular dsDNA molecules that were
mostly about half the size of CLCuV-PK dsDNA-A. They appeared to be derived from
CLCuV-PK DNA-A by various combinations of sequence deletion, duplication,
inversion and rearrangement and, in a few instances, insertion of sequences of
unknown origin. Each of ten tobacco plants contained a different predominant form
of such a defective molecule; however, all the forms contained the intergenic
region and part of the AC1 (Rep) gene. Some of the forms contained novel open
reading frames and might have a role in the evolution of variant geminiviruses.
The defective components were not detected at 3 months after the original culture
of CLCuV-PK was transmitted by whiteflies (Bemisia tabaci) from cotton to tomato
but were present after a further 6 months. They were transmitted, along with full
length DNA-A, between tobacco and tomato plants by grafting and by B. tabaci.
PMID- 9634095
TI - Use of modified plum pox virus coat protein genes developed to limit
heteroencapsidation-associated risks in transgenic plants.
AB - Aphid transmission of a non-aphid-transmissible strain of zucchini yellow mosaic
virus (ZYMV-NAT) occurs in transgenic plants expressing the plum pox potyvirus
(PPV) coat protein (CP) gene. Heteroencapsidation has been shown to be
responsible for this modification in the epidemiological characteristics of the
infecting virus. In order to prevent this biological risk, several modified PPV
CP constructs were produced that were designed to interfere with
heteroencapsidation itself or to block aphid transmission of heteroencapsidated
virions. These constructs were first expressed in Escherichia coli in order to
check for the accumulation of pseudo-particles by electron microscopy. Virus-like
particles (VLPs) were found with the full-length CP and with a PPV CP lacking the
DAG amino acid triplet involved in aphid transmission. However, no VLPs were
observed with CP lacking R220, Q221 or D264, amino acids known to be essential
for the assembly of other potyvirus CPs. Transgenic Nicotiana benthamiana lines
expressing the different PPV CP constructs were infected with ZYMV-NAT. Aphid
transmission assays performed with these plants demonstrated that the strategies
developed here provide an effective means of minimizing the biological risks
associated with heteroencapsidation.
PMID- 9634096
TI - Role of the helper component in vector-specific transmission of potyviruses.
AB - Four aphid species were tested for their ability to transmit tobacco etch (TEV)
and turnip mosaic (TuMV) potyviruses. Myzus persicae and Aphis gossypii
transmitted both viruses efficiently from infected plants, whereas Lipaphis
erysimi transmitted only TuMV and Myzus ascalonicus was a poor or non-transmitter
of either virus. Similar electrically monitored probing patterns were produced by
M. persicae, L. erysimi and M. ascalonicus, ruling out behavioural differences as
the cause of differential transmission. Transmission results similar to those
from infected plants were obtained when these aphids acquired homologous
virus/helper component (HC) mixtures through membranes. With heterologous
virus/HC mixtures, M. persicae remained a highly efficient vector and M.
ascalonicus a non-vector, but L. erysimi became an efficient vector of TEV if
acquired in the presence of TuMV HC and A. gossypii transmitted both viruses less
efficiently when acquired with TuMV HC. Transmission was highly correlated with
the retention of virus in the stylets, as determined by autoradiography of 125I
labelled virions. The results show that constituent(s) of or in the food canal of
different aphid species differ in their ability to interact with specific HCs,
leading to qualitative or quantitative differences in ability to retain and
subsequently transmit specific potyviruses.
PMID- 9634097
TI - Evidence that assembly of a potyvirus begins near the 5' terminus of the viral
RNA.
AB - A search for the first region in the genomic RNA of a potyvirus to be
encapsidated during the assembly of virus particles in vivo has been undertaken.
Protoplasts were collected at various times after inoculation and fragments of
viral RNA that were protected from nuclease degradation were isolated from
extracts and identified by RT-PCR procedures. Nuclease-resistant fragments of
viral RNA were not detected in protoplasts that had been infected for 30 min.
However, such fragments were present in protoplasts collected 40 min after
inoculation and these contained a region at or near the 5' terminus of the viral
RNA. Protoplasts that had been infected for 45 min or longer contained full
length viral RNA in a nuclease-resistant form. These results suggest that
assembly of virus particles begins with the interaction of coat protein subunits
with the 5' terminal region of progeny viral RNA molecules.
PMID- 9634098
TI - Citrus psorosis virus: nucleotide sequencing of the coat protein gene and
detection by hybridization and RT-PCR.
AB - Citrus psorosis virus (CPV) is a multicomponent ssRNA virus with a coat protein
of approximately 48 kDa. The viral genome is encapsidated in short and long
particles that are readily separated by sucrose density-gradient centrifugation.
CPV particles are spiral filaments that are referred to as spiroviruses (SV). A
cDNA library of purified short particles from isolate CPV-4 was prepared in a
Lambda vector and screened for expression of the coat protein gene (CPG) with a
monoclonal antibody to the coat protein. Sequencing of immunopositive clones
indicated a single ORF encoding a 49 kDa protein. This ORF, when expressed in E.
coli, gave a protein identical in size and immunoreactivity to the CPV coat
protein. A full-length clone of the CPG was transcribed and used in Northern
hybridization assays to establish that short particle RNA of CPV is negative
sense and contains the CPG. Moreover, the CPG was not found on RNA extracted from
long particles or on the sedimentable dsRNA from CPV infected tissue. RT-PCR
assays were developed for the amplification of a 600 bp fragment of CPG and for
the complete CPG (1317 bp). The 600 bp fragment from a biologically and
serologically different isolate, CPV-6, was cloned, sequenced and found to share
86% (nucleotide) and 96% (amino acid) identity with CPV-4. BLAST analysis of
sequences from CPV-4 and CPV-6 detected no significant nucleic acid or protein
similarity with any known viral sequences.
PMID- 9634099
TI - The nucleotide sequence of satellite tobacco necrosis virus strain C and helper
assisted replication of wild-type and mutant clones of the virus.
AB - The complete nucleotide sequence of satellite tobacco necrosis virus strain C
(STNV-C) was determined. The genome has a similar overall organization to two
STNV isolates studied previously but differs significantly from them in the
secondary structure of the translated and untranslated regions (UTRs). STNV-C RNA
is naturally uncapped and contains 1221 nt: 101 nt in the 5' UTR, 606 nt in the
capsid protein (CP) coding region and 514 nt in the 3' UTR. Using the known
sequences of STNV-C and tobacco necrosis virus strain D (TNV-D) RNAs, full-length
cDNA clones of both RNAs were constructed. Synthetic transcripts derived from
STNV-C cDNA clones only replicated in plants and protoplasts when co-inoculated
with TNV-D transcripts. A number of mutant clones in both the 3' and the 5' STNV
C RNA UTRs were constructed which disrupted putative cis-acting elements
recognized by helper virus polymerase. Deletion analysis revealed an essential
requirement of all 3' and 5' proximal sequences in the STNV-C UTRs for
replication. However, an internal region in the 3' UTR could be deleted without
loss of infectivity. Likewise, the entire STNV-C CP-encoding region could be
deleted and replaced with a marker gene of a similar size without loss of
transcript accumulation in plants.
PMID- 9634100
TI - The ecdysteroid UDP-glucosyltransferase gene of Autographa californica
nucleopolyhedrovirus alters the moulting and metamorphosis of a non-target
insect, the silkworm, Bombyx mori (Lepidoptera, Bombycidae).
AB - The Autographa californica nucleopolyhedrovirus (AcMNPV) does not infect the
silkworm and molecular studies on silkworm insusceptibility have not been
performed. In cultured cells of the silkworm, the expression of viral genes has
been reported. The expression of AcMNPV genes and their effect in vivo and in
vitro was studied. In this study, the early gene, the ecdysteroid UDP
glucosyltransferase (egt) gene of AcMNPV, which inactivates the insect moulting
hormone by sugar conjugation, was examined to determine whether it would alter
the growth of the silkworm. Using wild-type (wt) AcMNPV, the egt gene deletion
virus (vEGTDEL), and the virus carrying the egt promoter-lacZ cassette in vEGTDEL
(vEGTZ), the egt promoter-driven expression in cultured cells and in
nonproductive infection of the silkworm was characterized. Infection of cultured
cells with vEGTZ at three different doses occurred in a single cell manner. When
budded wt AcMNPV was injected into the fourth and fifth instar larvae, an
increase in the amount of virus occurred and caused abnormal larval growth, which
resulted in the prolongation or skipping of the larval instar, premature
pupation, or death during the pupal stage. For infection of the fourth instar
larvae, precocious metamorphosis was observed. When the same amount of vEGTDEL
was injected, the alteration of growth did not occur. These results suggest that
the egt gene was expressed in the primary infected cells of the silkworm, and
that the EGT was secreted into the haemocoel, which significantly altered larval
growth.
PMID- 9634101
TI - The single-nucleocapsid nucleopolyhedrovirus of Buzura suppressaria encodes a P10
protein.
AB - The p10 gene of Buzura suppressaria single-nucleocapsid nucleopolyhedrovirus
(BusuNPV) was identified by virtue of its localization downstream from the
Autographa californica (Ac) MNPV p26 homologue. The BusuNPV p10 gene encodes a
protein of 94 amino acids. The amino acid sequence contains domains
characteristic of baculovirus P10 proteins, e.g. a coiled-coil domain, a proline
rich motif and a positively charged C terminus. The highest amino acid homologies
were found with the Spodoptera littoralis (Spli) NPV and Spodoptera exigua (Se)
MNPV P10 proteins. An AcMNPV recombinant expressing the BusuNPV P10 formed
fibrillar structures in the cytoplasm of Spodoptera frugiperda cells. BusuNPV P10
could not fully replace AcMNPV P10 in its nuclear disintegration function, since
polyhedra were not efficiently liberated from infected cells late in infection.
The BusuNPV p26 gene encodes a protein of 263 amino acid residues with 70% amino
acid similarity with SeMNPV P26. Downstream of the BusuNPV p10 gene, the gene for
the occlusion-derived virus protein ODVP-6e is located. This is unlike the
situation in many other NPVs, including SeMNPV, where the p10 gene neighbours the
p74 gene. The data presented here suggest that although the p10 gene is not
conserved in sequence, evolutionary pressure preserves the structure of P10 and
hence its function. These data also indicate that all NPVs, MNPVs as well as
SNPVs, contain this gene.
PMID- 9634102
TI - Specificity of multiple homologous genomic regions in Spodoptera exigua
nucleopolyhedrovirus DNA replication.
AB - The region upstream of the Spodoptera exigua multicapsid nucleopolyhedrovirus
(SeMNPV) ubiquitin gene contains four near-identical 68-bp-long palindromic
repeats. This region, named Sehr6 and located at map unit (m.u.) 88 of the SeMNPV
genome on pSeEcoRI-2.2, showed structural homology to previously identified
homologous regions (hrs) in a number of other baculoviruses. Hrs function as
enhancers of transcription and as putative origins (oris) of baculovirus DNA
replication. Five additional hrs (Sehr1-Sehr5) were identified on the SeMNPV
genome by Southern blot hybridization with an 18-bp-long oligonucleotide
complementary to a sequence conserved within the arms of the four palindromic
repeats of Sehr6. Sehr1-Sehr6 were dispersed on the SeMNPV genome at m.u. 8.0,
30.0, 38.5, 51.0, 77.0 and 88.0, respectively. Sequence analysis of these hrs
confirmed the presence of palindromic repeats, highly similar to those found in
pSeEcoRI-2.2. The number of palindromes varied from one (Sehr4) to nine (Sehr1)
per hr. The Sehrs are all present in non-coding regions of the SeMNPV genome and
also contain multiple putative transcription recognition sequences. Plasmids
containing either of the Sehrs replicated in an SeMNPV-dependent DNA replication
assay. The Sehrs were unable to replicate in an AcMNPV-dependent DNA replication
assay. This was in contrast to the previously observed SeMNPV non-hr type ori,
which replicated in the presence of both AcMNPV and SeMNPV. These data suggest
that the replication of SeMNPV and the role of hrs in this process is highly
specific.
PMID- 9634103
TI - Alcoholism in the later years.
PMID- 9634104
TI - Geriatrics photo quiz. Meningioma.
PMID- 9634105
TI - Purple patches on the legs.
PMID- 9634106
TI - Atrial fibrillation: drug therapies for ventricular rate control and restoration
of sinus rhythm.
AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and its
prevalence increases with age. Etiologies include coronary artery disease,
hypertension, valvular heart disease, thyrotoxicosis, and other cardiac and
noncardiac conditions. AF can lead to reversible impairment of left ventricular
(LV) function, LV dilatation, clinical heart failure, angina pectoris, stroke,
and increased mortality. Digoxin, beta blockers, or calcium channel blockers are
used to control ventricular rate in new-onset AF with hemodynamically stable
rhythm and in chronic AF where rhythm cannot be restored. These drugs can be used
alone or in combination, depending on the clinical situation. The most complete
relief of symptoms occurs when sinus rhythm is restored. Class IA, IC, and III
antiarrhythmic agents can be used to restore and maintain sinus rhythm in
selected patients.
PMID- 9634107
TI - PACE: a model for integrated care of frail older patients. Program of All
inclusive Care for the Elderly.
AB - The Program of All-inclusive Care for the Elderly (PACE) is a model of care that
pools Medicare and Medicaid funds to provide acute and long-term care services
for older patients through the use of interdisciplinary teams. Services include
physician visits, prescription drugs, rehabilitation services, personal care
workers, hospitalization, and nursing home care, if needed. PACE programs may
also offer social services intervention, case management, respite care, or
extended home care nursing. The PACE site assumes financial responsibility for
all services. Now that PACE programs can become permanent providers under
Medicare, their number is expected to grow.
PMID- 9634108
TI - Geriatric rhinitis: what it is, and how to treat it.
AB - In the nose, normal physiologic changes of aging include loss of nasal tip
support, atrophy of mucus-producing mucosal glands, and decreased olfaction.
These changes contribute to geriatric rhinitis, the symptoms of which are often
attributed by the older patient to "allergies" or "sinus trouble." An
understanding of these anatomic changes, linked with a thorough history and
physical examination, allows the physician to properly manage geriatric rhinitis.
Medical management most often involves liquifying--not drying--nasal secretions
with oral and topical preparations. Conservative surgical treatment is
occasionally indicated.
PMID- 9634109
TI - Chilaiditi's syndrome: an unusual cause of chest or abdominal pain.
PMID- 9634110
TI - Benefits of screening mammography: a review for the primary care physician.
AB - BACKGROUND: Screening mammography, particularly for women in their 40s, has
become a confusing issue for many physicians. Recent scientific and political
controversies regarding screening guidelines have added to this confusion.
METHODS: Many randomized clinical trials have shown the benefits of mammographic
screening for women over the age of 50, and recent studies show a statistically
significant benefit for women in their 40s as well. Understanding the screening
controversy requires an understanding of the principle of screening for disease,
the epidemiology of breast cancer, and the results of the many randomized
clinical trials, particularly recent data from the Swedish two-county trials. An
appreciation of the improvements in mammographic quality in recent years, and in
the education of the radiologists who interpret these studies, will also heighten
clinical acceptance of this screening technique. RESULTS: Both the American
Cancer Society and American College of Radiology endorse annual mammographic
screening for women over age 40, and there is compelling evidence to support
these recommendations. CONCLUSION: Radiologists, primary care providers,
surgeons, and pathologists should work together to enhance the benefits of and
access to screening mammography.
PMID- 9634111
TI - Disability law: problems and proposals.
AB - BACKGROUND: Medically disabled persons have traditionally encountered obstacles
when seeking and maintaining employment. Integration of the medically disabled
worker is the goal of recent legislation that directs removal of physical
barriers and protects disabled workers from discrimination. The major force
driving this social policy is the Americans With Disabilities Act (ADA). METHODS:
Current disability laws and related judicial opinions are reviewed. Primary
attention is focused on the ADA. RESULTS: Legislation addressing employment
discrimination has serious deficiencies. Medical support of this important social
policy is hampered by vague statutory definitions and seemingly capricious
judicial opinions. CONCLUSION: Disability laws require precise language
identifying specific, qualifying medical conditions. The laws should require
comprehensive medical assessment that objectively establishes a connection
between a medical disorder and severe, sustained impairment. Some currently
included conditions, such as personality disorders, should be considered for
exclusion.
PMID- 9634112
TI - Does the proven benefit of mammography extend to breast cancer patients over age
70?
AB - BACKGROUND: Prospective randomized studies show reduced breast cancer mortality
among women offered mammographic screening; yet, few women 70 or older were
represented in these trials. We examine the impact of mammography on stage at
diagnosis of breast cancer, over the years when mammography came into general
use, comparing women aged 40 to 69 with those aged 70 and older. METHODS: We
reviewed the records of 1,001 consecutive patients 40 and older treated for
invasive or in situ breast cancer in the surgical practice of one of us (H.S.C.)
between 1979 and 1993, comparing trends in mammography use, means of diagnosis,
tumor size, axillary node status, and pathology. RESULTS: The proportion of cases
diagnosed by mammography increased over time to a comparable degree in both age
groups, as did the proportion of T1 and DCIS or microinvasive cancers. This trend
toward earlier stage appears entirely due to an increasing use of mammography.
CONCLUSION: The potential benefit of regular mammography to healthy women aged 70
and older may equal that observed in their younger counterparts.
PMID- 9634113
TI - Dynamic magnetic resonance imaging in evaluating suspicious breast lesions:
correlation with pathologic findings.
AB - BACKGROUND: We used dynamic magnetic resonance imaging (MRI) to study breast
lesions in 13 women. METHODS: We observed differences in contrast uptake between
benignancy and malignancy in 14 suspicious breast lesions. Three-dimensional (3D)
gradient echo sequences were obtained before and after administration of
gadolinium-based contrast medium (0.16 mmol/kg). The percentage of signal
increase in lesions was measured in a series of five 90-second sequences, and
time-enhancement patterns were correlated with pathologic diagnoses. RESULTS:
Seven benign lesions and three breast cancer recurrences showed less than 185%
signal increase at 90 seconds after contrast administration. Three new breast
cancers and one recently biopsied benign lesion showed more than 185% signal
increase at 90 seconds. CONCLUSION: Using this MRI technique, we can discriminate
between new breast cancers (more than 185% early signal increase) and breast
cancer recurrence and/or benign lesions (less than 185% early signal increase)
but cannot distinguish recurrent from benign lesions.
PMID- 9634114
TI - Risk factors for hip fracture among southern older women.
AB - BACKGROUND: Older women are considered at risk for hip fracture; fracture rates
are highest in the southern region of the United States. The purpose of this
study was to develop a predictive model for osteoporotic hip fracture among a
national sample of southern women aged 50 years and older. METHODS: Subjects were
participants in the Third National Health and Nutritional Examination Survey,
Phase 1. Data were collected by the National Center for Health Statistics.
Predictors examined included age, race, heredity, body mass index, physical
activity, smoking status, alcohol use, and dairy product use. RESULTS: The sample
consisted of 953 women aged 50 years and older. The predictive model included
older age, black race, Hispanic race, and low body mass index. CONCLUSIONS:
Recommendations emphasize weight gain for underweight women and promotion of
healthy body weights for women of all ages.
PMID- 9634115
TI - Implementation of early discharges after uncomplicated vaginal deliveries:
maternal and infant complications.
AB - BACKGROUND: Short-stay obstetric stays have been the recent focus of many social
and medical debates. We did a retrospective study of a large community teaching
hospital's experience in making a safe transition to short-stay obstetrics.
METHODS: Over a 10-month period, a multidisciplinary committee developed an
intrapartum and postpartum education program to allow short hospital stays after
uncomplicated vaginal deliveries. Computerized data were then retrieved on all
uncomplicated spontaneous vaginal deliveries (DRG 373) from January 1994 to March
1995. RESULTS: During the study period, 554 women were discharged on the first
postpartum day, resulting in three maternal readmissions and nine pediatric
readmissions (combined readmission rate of 2.2%). This low readmission rate
compared favorably with our experience with 2,563 uncomplicated vaginal
deliveries from January 1991 to December 1993, immediately before the institution
of the short-stay obstetrics program (combined readmission rate of 3.9%). The
average hospital cost for a 1-day stay was $1,714 compared with $2,477 for a 2-
to 3-day stay, representing a saving of only 31%. CONCLUSIONS: Early obstetric
discharges after an uncomplicated spontaneous vaginal delivery can be safe and
effective with appropriate patient selection and support.
PMID- 9634116
TI - HIV-1-associated Kaposi's sarcoma in a predominantly black population at an inner
city hospital.
AB - BACKGROUND: Kaposi's sarcoma (KS) associated with human immunodeficiency virus
type 1 (HIV-1) is the most common malignancy in patients with AIDS. It has been
most commonly reported in white homosexual men, though a few cases have been
reported in blacks. METHODS: We conducted a retrospective analysis of all HIV-1
seropositive patients with biopsy-proven KS seen at Howard University Hospital
between February 1985 and June 1995. RESULTS: Of the 73 patients identified, 66
(90%), 4 were white, 2 were Hispanic, and 1 was of unidentified race. The median
age was 32 years. Forty-eight (66%) were homosexual or bisexual men, and 10 (14%)
were homosexual or bisexual with a history of intravenous drug use (IDU). A
history of IDU or blood transfusion was the only risk factor in 7 (9%) and 2
(3%), respectively. The other 6 (8)% were heterosexual. The median survival was
2.2 years. A CD4 count <200 and the presence of an opportunistic infection were
associated with shortened survival. CONCLUSIONS: The predominant risk factor for
HIV-1-associated KS was homosexual or bisexual activity. Only a few women with KS
were identified, and they also reported sexual transmission from male bisexuals
and/or drug users. Poor survival was associated with CD4 <200, stage III and IV
KS at presentation, and opportunistic infections.
PMID- 9634117
TI - The level of preventive health care in an internal medicine residency clinic:
still only an ounce of prevention?
AB - BACKGROUND: Clinical prevention is a critical component of primary care residency
training. How well residents do preventive services is one measure of the
adequacy of their training. METHODS: To assess the level of preventive health
care in a university internal medicine residency clinic, we conducted a
randomized retrospective review of 225 patient records. RESULTS: We documented
preventive services in only 39% of potentially appropriate instances. Cholesterol
screening occurred in 53% of eligible cases, breast examination in 41%, mammogram
in 69%, Papanicolaou's smear in 53%, estrogen replacement therapy (ERT) in 41%,
fecal occult blood testing in 30%, flexible sigmoidoscopy in 18%, influenza
vaccination in 65%, pneumococcal vaccination in 44%, and tetanus immunization in
only 9%. Male residents were significantly less likely than females to order
mammograms or offer ERT. CONCLUSIONS: Compared to earlier studies of similar
design, we found that the level of preventive health care has improved during
residency training, but remains unacceptably low.
PMID- 9634118
TI - Maternity care practices of navy family practice residency graduates after
leaving the military.
AB - BACKGROUND: Nationwide, 32% of residency-trained family physicians deliver babies
compared with 73% to 90% in the military. This study describes and defines issues
that could ultimately help revive family practice maternity care. METHOD: We
surveyed 112 family physicians who had left the navy. RESULTS: Ninety-one percent
had delivered babies in the navy, 45% since leaving the military, and 25%
currently. Principal maternity care incentives both in and out of the military
were personal and professional satisfaction. Reasons for not providing civilian
maternity care included malpractice risks, insurance costs, and lifestyle issues.
The decision for providing maternity care was usually made before or during
residency, whereas the decision against was most often made upon leaving the
military. Among more recent graduates (1990-1995), 48% continued to deliver
babies in civilian practice. (This is about 20% more than recent civilian
graduates.) Malpractice concerns were less important to this group than to
earlier graduates. CONCLUSIONS: Factors discouraging family physicians from
providing maternity care arise from their practice environment and are not easily
overcome with improved training and experience. Recent navy residency graduates
are not as easily discouraged.
PMID- 9634119
TI - Patient-controlled anesthesia for colonoscopy using propofol: results of a pilot
study.
AB - BACKGROUND: We studied the feasibility of using patient-controlled anesthesia
(PCA) for conscious sedation during colonoscopy. METHODS: Patients having
elective colonoscopy had medications delivered in bolus fashion by PCA pump
(Abbot Lifecare Provider 5500 Infusion System). Four patients received propofol
as 20 mg/dose boluses, and four patients received propofol in a 0.3 mg/kg/dose.
Twelve patients received propofol at 0.2 mg/kg/dose with alfentanil at 4
microg/kg/dose. RESULTS: There were no clinically unacceptable changes in
continuously monitored blood pressure, pulse rate, ECG, or respiratory rate.
There were no adverse effects from the sedation and no complications due to
colonoscopy. Recovery time was rapid, but recall persisted in most subjects. Pain
and overall discomfort in patients given propofol only were rated as moderate by
most subjects. CONCLUSION: Patient-controlled anesthesia is feasible for use in
endoscopic sedation. Propofol alone did not allow adequate pain relief, but
propofol and alfentanil together seemed to provide good control of pain.
PMID- 9634120
TI - The red eye revisited: ophthalmia nodosa due to tarantula hairs.
AB - We present the case of a 17-year-old girl who came to our center with a red
irritated eye from exposure to tarantula hairs. An ophthalmology literature
search revealed six reported cases. There have been no reports of these cases in
the general medical and pediatric literature. Due to the increasing popularity of
tarantulas as pets, we present the following case report and discussion to bring
attention to this potential complication of tarantula handling.
PMID- 9634121
TI - Colonic strictures induced by nonsteroidal anti-inflammatory drugs.
AB - Long-term use of nonsteroidal anti-inflammatory drugs has been reported to cause
small bowel and colonic ulcerations and strictures. Abdominal pain, change in
bowel habits, and anemia are frequently present, mimicking other inflammatory and
neoplastic diseases of the gut. We report two cases of drug-induced colonic
stricture that illustrate two different spectrums of this disease. The first is a
case of ascending colon ulcerated strictures and severe anemia managed
conservatively, and the second is a chronic variant with obstructive-type
symptoms and a tight nonulcerated colonic stricture that necessitated right
hemicolectomy.
PMID- 9634122
TI - Prolonged prostate-specific antigen response in flutamide withdrawal syndrome
despite disease progression.
AB - Flutamide withdrawal syndrome is characterized by a decrease in prostate-specific
antigen (PSA) after flutamide withdrawal in a subset of patients with progressing
metastatic carcinoma of the prostate. It is generally hypothesized to be due to a
point mutation in the androgen receptor that allows the antiandrogen to function
as an agonist, leading to a dramatic and rapid PSA response. We describe a
patient with androgen-independent prostate cancer in whom PSA continued to
decrease for a period of 15 months after flutamide withdrawal. With continuing
fall in PSA, the patient had unequivocal progression of disease seen on bone
scan. This case illustrates the potential decoupling of PSA response from disease
status in flutamide withdrawal. It also illustrates the need for continued
clinical evaluation of patients with metastatic prostate cancer, even in the face
of PSA response.
PMID- 9634123
TI - Cavernous sinus syndrome due to metastatic renal cell carcinoma.
AB - We describe a 49-year-old woman with a history of metastatic renal cell carcinoma
and classic signs and symptoms of left-sided cavernous sinus syndrome. Magnetic
resonance imaging showed a lesion in the left cavernous sinus consistent with
metastatic renal cell carcinoma. The patient received radiation therapy totaling
4,600 cGy, with complete resolution of symptoms. This represents the first case
report of renal cell carcinoma metastatic to the left cavernous sinus.
PMID- 9634124
TI - Schistosomiasis of the urinary bladder in an African immigrant to North Carolina.
AB - A 30-year-old black man came to the emergency department with gross hematuria,
prostatitis, and urethritis 4 months after immigrating to this country from the
Sudan in Africa. Urinalysis revealed hematuria and no ova or parasites. An
intravenous urogram showed normal kidneys and ureters. The patient had cystoscopy
with biopsies of an inflamed and ulcerated bladder mucosa. The nematode
Schistosoma haematobium and schistosome eggs were identified without evidence of
urothelial malignancy. The patient was treated with praziquantel and is currently
asymptomatic. Over 200 million people are infected with schistosomiasis
worldwide, yet this disease is rarely encountered in this country. The
differential diagnosis and assessment of patients must include exposure to
uncommon diseases that are endemic to other geographic regions.
PMID- 9634125
TI - CD5 negative diffuse mantle cell lymphoma with splenomegaly and bone marrow
involvement.
AB - We report the case of a 78-year-old man in whom routine physical examination
revealed cervical adenopathy and splenomegaly. Peripheral blood showed a normal
white blood cell count with an absolute lymphocytosis, which included a
population with slightly indented nuclei. Lymph node biopsy showed morphology
compatible with mantle cell lymphoma. Bone marrow biopsy showed replacement by a
lymphoid proliferation composed of lymphocytes with features similar to those
found in the peripheral blood. Immunophenotypic analysis of both peripheral blood
and lymph node showed positivity for CD19, CD20 and CD22, with lambda light chain
restriction. Tests for CD5 and CD10 were negative. Cytogenetic analysis and
polymerase chain reaction studies confirmed the presence of t(11,14) supporting a
diagnosis of mantle cell lymphoma. This unusual case of CD5-negative mantle cell
lymphoma exemplifies the importance of combined molecular, cytogenetic, and
morphologic evaluation when confronted with a lymphoma having an atypical
phenotype.
PMID- 9634126
TI - Laryngeal manifestations of vasculitic disease.
AB - Vasculitis can involve the larynx in 4% to 10% of cases and can cause arthritis,
edema, or upper airway obstruction within the larynx. Since most of these
laryngeal manifestations are nonspecific, the clinician needs to keep a high
index of suspicion when a patient complains of hoarseness or laryngeal discomfort
and chronic constitutional symptoms. We present a case of crescentic
glomerulonephritis associated with antineutrophil crytoplasmic autoantibody
(ANCA). In addition, we discuss the usefulness and indications of ANCA serology
and review multiple laryngeal manifestations that have been associated with
common vasculitides and reported in the medical literature.
PMID- 9634127
TI - Endometrial stromal sarcoma with sex cord-like differentiation associated with
tamoxifen therapy.
AB - Low-grade endometrial stromal sarcoma with sex cord-like differentiation occurred
in two postmenopausal patients who had received tamoxifen for more than 3 years
after surgical resection for breast cancer. Uterine sarcomas have been described
in association with the use of tamoxifen. Only two cases of endometrial stromal
sarcoma with sex cord-like features associated with tamoxifen use have been
reported previously. This report adds an additional two cases of this tumor.
Immunohistochemical and ultrastructural examinations of the tumor support the
concept of smooth muscle differentiation in the sex cord-like areas. This
observation proposes that the low-grade endometrial stromal sarcoma with sex cord
like elements may be a consequence of tamoxifen ingestion, but the exact
mechanism of tamoxifen in the development of this tumor remains speculative.
PMID- 9634128
TI - Sunscreens and skin cancer.
PMID- 9634129
TI - Intermittent fever and pancytopenia.
PMID- 9634130
TI - Giant skin cancers.
PMID- 9634131
TI - Social anxiety among adolescents: linkages with peer relations and friendships.
AB - This study examined the utility of modifying the Social Anxiety Scale for
Children-Revised (SASC-R) for use with adolescents, and examined associations
between adolescents' social anxiety (SA) and their peer relations, friendships,
and social functioning. Boys (n = 101) and girls (n = 149) in the 10th through
12th grades completed the Social Anxiety Scale for Adolescents (SAS-A) and
measures of social support, perceived competence, and number and quality of their
best friendships. Factor analysis of the SAS-A confirmed a three-factor
structure: Fear of Negative Evaluation, Social Avoidance and Distress in General,
and Social Avoidance Specific to New Situations or Unfamiliar Peers. Girls
reported more SA than boys, and SA was more strongly linked to girls' social
functioning than boys'. Specifically, adolescents with higher levels of SA
reported poorer social functioning (less support from classmates, less social
acceptance), and girls with higher levels of SA reported fewer friendships, and
less intimacy, companionship, and support in their close friendships. These
findings extend work on the SASC-R to adolescents, and suggest the importance of
SA for understanding the social functioning and close friendships of adolescents,
especially girls.
PMID- 9634132
TI - The development of early externalizing problems among children from low-income
families: a transformational perspective.
AB - The present study examined pathways leading to early externalizing problems from
age 1 to 3 1/2 in a design that took advantage of our knowledge of normative
progression and normative socialization as well as findings from research on
risk. A sample of 130 low-income participants was followed longitudinally from 12
to 42 months using observational measures of developmentally salient parenting
and child disruptive behavior to predict early externalizing problems. Results
are best accommodated by concepts such as transformation and transaction from
developmental psychology. For boys, both child and parent variables predicted
later externalizing. For girls and boys, the interaction between child
noncompliance and maternal rejection was significant.
PMID- 9634133
TI - Racial differences on the Conners Teacher Rating Scale.
AB - Factor congruence and mean differences on the Conners Teacher Rating Scale were
assessed across African-American and Caucasian school children. Factor analyses
conducted separately by gender revealed similar factors across races for males
and females. The main differences in factor structure within gender were the
presence of an Antisocial factor in black males and an Inattention factor in
white females. Across both males and females, teachers tended to rate black
children higher than white children on factors relating to externalizing
behaviors. Whether mean differences are a result of teacher bias or actual
behavioral differences in the classroom needs further research.
PMID- 9634134
TI - Cumulative risk across family stressors: short- and long-term effects for
adolescents.
AB - This study examined the relationship between number of family risk factors during
adolescence and three areas of psychosocial adjustment (internalizing problems,
externalizing problems, and academic achievement) in adolescence and 6 years
later in young adulthood. Risk factors examined included parental divorce,
interparental conflict, maternal physical health problems, maternal depressive
mood, and mother-adolescent relationship difficulties. The findings indicated
both concurrent and long-term associations between number of family risk factors
and psychosocial adjustment; however, the results differed based on area of
adjustment examined and whether concurrent or longitudinal data were considered.
Furthermore, a steep increase in adjustment difficulties occurred when number of
risk factors increased from three to four. The results are discussed in the
framework of four hypotheses which were tested, and clinical implications are
delineated.
PMID- 9634135
TI - Determinants of harsh parenting in Mexico.
AB - This paper presents a structural model of the determinants of harsh parenting
among Mexican mothers. One hundred five mothers (46 from the community; 59
referred to agencies for child maltreatment) were recruited from Sonora
(Northern) Mexico and interviewed. In this model the use of physical punishment
was explained by (1) authoritarian parenting style (mothers' beliefs concerning
the effective use of physical punishment and mothers' lack of disciplinary
skills) and (2) family dysfunction (a latent variable constructed from reports of
interspousal violence and the parents' use of alcohol and drugs). In addition,
the indirect effects of demographic and historical variables on harsh parenting
was included. The findings show that the most important factor influencing the
use of physical punishment in these families was authoritarian parenting style,
exerting a significant direct effect on the mothers' reports of their use of
harsh punishment. Family dysfunction had an indirect effect through parenting
style. Some sociodemographic variables also indirectly influenced the use of
beliefs maternal punishment It is concluded that cultural beliefs play a major
role in parenting within the framework of Mexican family relations.
PMID- 9634136
TI - Obtaining systematic teacher reports of disruptive behavior disorders utilizing
DSM-IV.
AB - This study examines the psychometric properties of the Vanderbilt AD/HD
Diagnostic Teacher Rating Scale (VADTRS) and provides preliminary normative data
from a large, geographically defined population. The VADTRS consists of the
complete list of DSM-IV AD/HD symptoms, a screen for other disruptive behavior
disorders, anxiety and depression, and ratings of academic and classroom behavior
performance. Teachers in one suburban county completed the scale for their
students during 2 consecutive years. Statistical methods included (a) exploratory
and confirmatory latent variable analyses of item data, (b) evaluation of the
internal consistency of the latent dimensions, (c) evaluation of latent structure
concordance between school year samples, and (d) preliminary evaluation of
criterion-related validity. The instrument comprises four behavioral dimensions
and two performance dimensions. The behavioral dimensions were concordant between
school years and were consistent with a priori DSM-IV diagnostic criteria.
Correlations between latent dimensions and relevant, known disorders or problems
varied from .25 to .66.
PMID- 9634137
TI - The relationship between peer status and depressive symptoms in children and
adolescents.
AB - The purpose of this study was to examine the relationship between specific
symptoms of depression and particular styles of peer difficulties. Participants
were 1687 students in fourth, sixth, seventh, eighth, ninth, and eleventh grades
from a midsized Midwestern city. Based on previous studies, it was hypothesized
that rejected and neglected youths would report greater depressive symptomatology
than other peers. In addition, aggressive-rejected youth were predicted to report
more Interpersonal Problems while submissive-rejected youths were expected to
report more Anhedonia. There were no sociometric group differences on global
scores of depression as measured by the Children's Depression Inventory; however,
the aggressive- and submissive-rejected youths did report specific differences.
Aggressive-rejected youths reported more Interpersonal Problems and feelings of
Ineffectiveness, while the neglected and submissive-rejected youths reported more
Anhedonia. Taken together, such differences provide support for differentiating
among types of rejected students and suggest that different interventions may be
necessary to address the needs of these youths.
PMID- 9634138
TI - Anatomical and neurochemical definition of the nucleus of the stria terminalis in
Japanese quail (Coturnix japonica).
AB - This study in birds provides anatomical, immunohistochemical, and hodological
data on a prosencephalic region in which the nomenclature is still a matter of
discussion. In quail, this region is located just dorsal to the anterior
commissure and extends from the level of the medial part of the preoptic area at
its most rostral end to the caudal aspects of the nucleus preopticus medialis. At
this caudal level, it reaches its maximal elongation and extends from the ventral
tip of the lateral ventricles to the dorsolateral aspects of the paraventricular
nucleus. This area contains aromatase-immunoreactive cells and a sexually
dimorphic population of small, vasotocinergic neurons. The Nissl staining of
adjacent sections revealed the presence of a cluster of intensely stained cells
outlining the same region delineated by the vasotocin-immunoreactive structures.
Cytoarchitectonic, immunohistochemical, and in situ hybridization data support
the notion that this area is similar and is probably homologous to the medial
part of the nucleus of the stria terminalis of the mammalian brain. The present
data provide a clear definition of this nucleus in quail: They show for the first
time the presence of sexually dimorphic vasotocinergic neurons in this region of
the quail brain and provide the first detailed description of this region in an
avian species.
PMID- 9634140
TI - Dual morphology and topography of the corticothalamic terminals originating from
the primary, supplementary motor, and dorsal premotor cortical areas in macaque
monkeys.
AB - In the motor, somatosensory, and auditory systems of rodents and cats, the
corticothalamic connection is composed of a main projection formed by small
endings and a minor projection terminating with giant endings. To establish
whether the corticothalamic projection originating from motor cortical areas in
primates exhibits the same duality, the anterograde tracer biotinylated dextran
amine was injected in eight macaque monkeys in the primary motor (M1; n = 3), the
supplementary motor (SMA; n = 3) and the dorsal premotor (PMd; n = 2) cortical
areas to label corticothalamic axons. The corticothalamic projection originating
from these three motor cortical areas was characterized by the presence of axon
terminals constituting the same two types of endings, observed both as boutons en
passant and terminaux. The population of small endings exhibited a mean cross
sectional maximum diameter of 0.95 microm (S.D. = 0.23), a range of diameters not
overlapping that of giant endings (mean diameter = 3.46 microm, S.D. = 0.74
microm). Topographically, the giant endings originating from M1 were located in
the same thalamic nucleus (ventroposterolateral nucleus, oral part) in which the
small endings were found. In contrast, the giant endings originating from SMA and
PMd were located in a thalamic nucleus (mediodorsal nucleus) distinct from the
main termination zone formed by small endings. Along the rostrocaudal axis, the
giant endings were distributed in a restricted zone, irrespective of the origin
of the projection (M1, SMA, PMd). The dual morphology of corticothalamic endings,
previously found in rodents and cats, is present in the motor system of subhuman
primates for both primary and nonprimary motor cortical areas.
PMID- 9634139
TI - Characterization of spinal motoneuron degeneration following different types of
peripheral nerve injury in neonatal and adult mice.
AB - Experimental lesions have been used widely to induce motoneuron (MN) degeneration
as a model to test the ability of different trophic molecules to prevent lesion
induced alterations. However, the morphological mechanisms of spinal MN death
following different types of lesions is not clear at the present time. In this
study, we have characterized the morphological characteristics of MN cell death
by examining DNA fragmentation and the ultrastructural and light microscopic
morphological features of MNs following different types of spinal nerve injury
(i.e., axotomy and avulsion) in the developing and adult mouse. In neonatal mice,
axotomy induced cell death as well as the atrophy of MNs that survived the
injury. DNA fragmentation could be detected by using the terminal
deoxynucleotidyl transferase (TUNEL) method during the cell death process
following neonatal axotomy, whereas TUNEL labeling was not observed following
either neonatal or adult avulsion. However, with the exception of TUNEL labeling,
the morphological characteristics of MN death following neonatal axotomy and
avulsion were similar, and both resembled most closely the form of programmed
cell death termed cytoplasmic or type 3B, which exhibits similarities as well as
differences with currently accepted definitions of apoptosis. By contrast, adult
avulsion resulted in a type of degeneration that resembled necrosis more closely.
However, even there, the morphology was mixed, showing characteristics of both
apoptosis and necrosis. These results indicate that the mode of MN degeneration
is complex and is related to developmental age and type of lesion.
PMID- 9634141
TI - Seasonal plasticity and sexual dimorphism in the avian song control system:
stereological measurement of neuron density and number.
AB - Differences in neuron density and number are associated with seasonal plasticity
and sexual dimorphism in the avian song control system. In previous studies,
neuron density and number in this system have been quantified primarily through
nonstereological approaches in thick tissue sections by using the nucleolus as
the unit of count. The reported differences between seasons and sexes may be
inaccurate due to biases introduced by neuron splitting during sectioning. We
used the unbiased optical disector technique on tissue from three previous
studies (two investigations of seasonal plasticity and one investigation of
sexual dimorphism in avian song nuclei) to assess seasonal and sex differences in
neuron density and number. In two song nuclei, HVc and the robust nucleus of the
archistriatum (RA), the optical disector yielded intergroup differences in neuron
density and number that coincided well with the three previous reports. We also
estimated neuron number and density with a random, systematic, nonstereological
counting protocol that used the neuronal nucleolus as the unit of count. We
compared this method directly to the optical disector. In all cases, the two
neuron-counting methods produced similar estimates of neuron number and density;
the differences between treatment groups were equally discernible regardless of
the counting method used. This study confirms previously reported seasonal and
sex differences in the HVc and the RA by use of stereology and indicates that a
random, systematic, nonstereological neuron-counting protocol is accurate and is
well suited to the study of these phenomena in the avian song control system.
PMID- 9634142
TI - Induction of MAP1B phosphorylation in target-deprived afferent fibers after
kainic acid lesion in the adult rat.
AB - We have previously shown that the phosphorylated form of microtubule-associated
protein 1B (MAP1B-P), which is located in growing axons during development and
regeneration, remains detectable in the adult central nervous system only in
areas that undergo morphologic plasticity (Nothias et al. [1996] J. Comp. Neurol.
368:317-334). Our objective in the present study was to determine whether lesion
induced axonal remodeling, in the adult rat, is associated with reinduction of
MAP1B phosphorylation. MAP1B-P was not detectable in intact adult thalamic
ventrobasal complex (VB), although low levels of MAP1B and its mRNA were present.
A neuron-depletion of VB by in situ injection of kainic acid was followed by an
induction of MAP1B phosphorylation by 24 hours postlesion. MAP1B-P was detected
in fibers originating from undamaged neurons that were not located in the lesion,
as demonstrated by the absence of hybridized MAP1B-mRNA. Ultrastructural analysis
confirmed the exclusive location of MAP1B-P in axons in a proximodistal gradient.
MAP1B phosphorylation appeared to be regulated by posttranslational modification
of existing protein because the levels of MAP1B-mRNA did not change. The number
of MAP1B-P-labeled fibers increased during the first month postlesion and
remained high for a long period. Double staining by using axonal tracing with
dextran-biotin and tyrosine hydroxylase immunohistochemistry, showed the presence
of MAP1B-P in VB afferents from somatosensory relays and the locus coeruleus.
This study supports the hypothesis that MAP1B, at a particular state of
phosphorylation, is correlated with axonal remodeling in the adult central
nervous system (CNS). We suggest that the interaction of MAP1B-P with
microtubules allows the modulation of their dynamic properties during periods of
increased axonal plasticity.
PMID- 9634143
TI - Loss of primary sensory neurons in the very old rat: neuron number estimates
using the disector method and confocal optical sectioning.
AB - Loss of neurons has been considered to be a prime cause of nervous disturbances
that occur with advancing age. However, the notion of a constitutive aging
related loss of neurons has been challenged recently in several studies that used
up-to-date methods for counting neurons. In this study, we have applied
stereological techniques with the objective of obtaining quantitative data on
total neuron numbers and the distribution of neuron cross-sectional areas in the
fifth cervical (C5) and fourth lumbar (L4) dorsal root ganglion (DRG) of 3- and
30-month-old Sprague-Dawley rats. Tissue data were recorded on a confocal laser
scanning microscope with the use of the optical-disector technique and random,
systematic sampling. Aged rats of both sexes disclosed only a small decrease
(approximately 12%) in the number of cervical and lumbar DRG neurons.
Furthermore, there was no significant correlation between the degree of neuron
loss and the extent of behavioral deficits among the aged individuals. The DRG
neurons of aged rats had a smaller mean cross-sectional area (approximately 15%;
P < 0.001) at both DRG levels. Further analysis of the male cohorts was carried
out by using isolectin B4 and neurofilament subunit (phosphorylated 200 kDa;
RT97) immunoreactivity (IR) as selective markers for unmyelinated and myelinated
axons, respectively, and disclosed no significant change in the relative
frequencies of immunoreactive neuron profiles in the old rats. However, RT97-IR
DRG neurons of the aged rats had significantly smaller cross-sectional areas
(approximately 9% in C5; approximately 16% in L4; P < 0.001) than the young adult
rats, indicating a selective cell body atrophy among myelinated primary afferents
during aging. The results indicate that loss of primary sensory neurons cannot
exclusively explain the functional deficits in sensory perception among senescent
individuals. It seems likely that other factors at the subcellular level and/or
target interaction(s) contribute substantially to the sensory impairments
observed with advancing age.
PMID- 9634144
TI - Dendritic spines containing mu-opioid receptors in rat striatal patches receive
asymmetric synapses from prefrontal corticostriatal afferents.
AB - Prefrontal corticostriatal afferents to the caudate-putamen nucleus (CPN) have
been implicated in motor and cognitive functions that are subject to opioid
modulation through the mu-opioid receptor (MOR). We examined the cellular basis
for this modulation by combining anterograde transport of biotinylated dextran
amine (BDA) following injections into the rat prefrontal cortex with
immunocytochemical detection of MOR in patch compartments of the CPN. The BDA
labeled neurons in deep layer V and layer VI of the dorsal part of the anterior
cingulate cortex and the medial agranular cortex projected bilaterally, with an
ipsilateral predominance, to MOR-enriched patches in the dorsomedial and
dorsocentral CPN, respectively. BDA-labeled terminals often apposed MOR
immunoreactive dendrites and perikarya but formed exclusively asymmetric,
excitatory-type synapses mainly with dendritic spines. Of the total anterogradely
labeled axon terminals forming asymmetric synapses, 40% (151 of 377) were with
MOR-labeled spines, and 58% (220 of 377) were with unlabeled dendritic spines. In
addition, immunogold-silver particles for MOR were seen in 14% (134 of 938) of
all BDA-labeled axons and axon terminals. These dually labeled axon terminals
also formed asymmetric synapses with dendritic spines that contained MOR
immunoreactivity. The proportions of BDA-labeled axon terminals forming
asymmetric synapses with MOR-labeled or unlabeled spines were similar in the CPN
ipsilateral and contralateral to the cortical injections. These results suggest
that, in patch compartments of the CPN, MOR plays a critical role in postsynaptic
response to, but also in presynaptic modulation of, prefrontal corticostriatal
excitation.
PMID- 9634145
TI - Metamorphic control of cyclic guanosine monophosphate expression in the nervous
system of the tobacco hornworm, Manduca sexta.
AB - During metamorphosis of Manduca sexta, defined sets of neurons show a dramatic
accumulation of cyclic guanosine monophosphate (cGMP). Although many of these
cells show low but detectable levels of cGMP during specific developmental
windows, these levels are enhanced dramatically during dissection of the central
nervous system (CNS). The ability of these neurons to show this induced cGMP
expression depends on the developmental stage. Larvae do not show this capacity
but it appears during the transition from the larval to the pupal stage. There
are two different classes of response: the early expressing neurons start to show
a cGMP response at the beginning of the prepupal stage while the late expressing
cGMP neurons start at different times during the pupal-adult transition. The
former set includes larval neurons that will likely be remodeled during
metamorphosis, and a number of them are serotonergic. The late-expressing group
also includes some larval cells, but most are adult-specific neurons. At least
for one adult-specific cluster, the antennal lobe neurons, the cGMP expression
parallels the maturation phase of these cells.
PMID- 9634146
TI - Sequence and expression of glutamic acid decarboxylase isoforms in the developing
zebrafish.
AB - We describe the isolation two glutamic acid decarboxylase (GAD) cDNAs from
zebrafish with over 84% identity to human GAD65 and GAD67. In situ hybridization
studies revealed that both GAD65 and GAD67 were expressed in the early zebrafish
embryo during the period of axonogenesis, suggesting a role for GABA prior to
synapse formation. Both GAD genes were detected in the telencephalon, in the
nucleus of the medial longitudinal fasciculus in the midbrain, and at the border
regions of the rhombomeres in the rostral hindbrain. In the caudal hindbrain,
only GAD67 was detected (in neurons with large-caliber axons). In the spinal
cord, both GAD genes were detected in dorsal longitudinal neurons, commissural
secondary ascending neurons, ventral longitudinal neurons, and Kolmer-Agduhr
neurons. Immunohistochemistry for gamma-aminobutyric acid (GABA) revealed that
GABA is produced at all sites of GAD expression, including the novel cells in the
caudal hindbrain. These results are discussed in the context of the hindbrain
circuitry that supports the escape response. We conclude that fish, like mammals,
have two GAD genes. The zebrafish GAD65 and GAD67 are present in identified
neurons in the forebrain, midbrain, hindbrain, and spinal cord, and they catalyze
the production of GABA in the developing embryo.
PMID- 9634147
TI - Regeneration of the newt retina: order of appearance of photoreceptors and
ganglion cells.
AB - The adult newt regenerates a functional retina following removal or destruction
of the original retina. We studied the order of appearance of cell types in the
regenerating retina by using immunohistochemical techniques. An antibody that
recognizes the alpha subunit (260 kDa) of voltage-dependent Na+ channels was
found to label a 255-kDa band in Western blots of crude membrane fractions from
the normal retina. Cryosections of normal retina revealed intense Na+ channel
immunoreactivity in somata and axons of ganglion cells, weaker immunoreactivity
in somata of amacrine cells, and no immunoreactivity in the inner plexiform
layer. In the same sections, immunoreactivity to a monoclonal antibody (RB-1)
specific to newt cones was intense in the photoreceptor layer. In regenerating
retinas, double staining with the Na+ channel antibody as a possible marker of
ganglion cells and RB-1 antibody first revealed immunoreactive cells at the
intermediate stage (three to five cells thick), which does not exhibit segregated
synaptic layers. Na+ channel-immunoreactive ganglion cells appeared before the RB
1-immunoreactive photoreceptors. Because ganglion cells also appear before
photoreceptor cells in normal development, common mechanisms may control both the
generation and the regeneration of the newt retina.
PMID- 9634148
TI - The need for depot atypical antipsychotics in the U.S.
PMID- 9634149
TI - Maryland's Medicaid reform: design and development.
PMID- 9634150
TI - Maryland's Medicaid reform: a provider's perspective.
PMID- 9634151
TI - Maryland's Medicaid reform: Will the gain outweigh the pain?
PMID- 9634152
TI - The structure of psychiatrists' outpatient practice.
PMID- 9634153
TI - The downside of the family-organized mental illness advocacy movement.
PMID- 9634154
TI - Why consumers and family advocates must work together.
PMID- 9634155
TI - Cultural sensitivity and aging.
PMID- 9634156
TI - Policy reform dilemmas in promoting employment of persons with severe mental
illness.
AB - Recent evaluations by the U.S. General Accounting Office and the National
Alliance for the Mentally Ill of reemployment efforts of the federal-state
vocational rehabilitation program found that services offered by state vocational
rehabilitation agencies do not produce long-term earnings for clients with
emotional or physical disabilities. This paper examines reasons for these poor
outcomes and the implications of recent policy reform recommendations. Congress
must decide whether to take action at the federal level to upgrade programs
affecting persons with severe mental illnesses or to continue to rely on state
decision making. The federal-state program largely wastes an estimated $490
million annually on time-limited services to consumers with mental illnesses.
Rechanneled into a variety of innovative and more appropriate integrated services
models, the money could buy stable annual vocational rehabilitation funding for
62,000 to 90,000 consumers with severe mental illnesses. Larger macrosystem
problems involve the dynamics of the labor market that limit job opportunities
and the powerful work disincentives for consumers with severe disabilities now
inherent in Social Security Disability Insurance, Supplemental Security Income,
Medicare, and Medicaid.
PMID- 9634157
TI - A randomized controlled study of the effectiveness of intensive outpatient
treatment for cocaine dependence.
AB - OBJECTIVE: A randomized controlled study design was used to compare the
effectiveness of intensive outpatient treatment with individual outpatient
counseling and a combination of individual and group outpatient counseling for
cocaine-dependent patients. METHODS: Volunteers for this study were recruited
from among first admissions to an inner-city, public-sector outpatient substance
abuse clinic. In-treatment, end-of-treatment, and nine-month follow-up
assessments were compared for participants randomly assigned for 12 weeks to one
of three treatment modalities--weekly individual outpatient counseling, weekly
individual counseling plus one weekly group session, or a newly designed
intensive group treatment program consisting of three hours of group treatment
three days a week. RESULTS AND CONCLUSIONS: Patients who completed the intensive
program showed significant improvement from intake to end-of-treatment scores on
the Addiction Severity Index, the Beck Depression Inventory, and the Symptom
Checklist. At nine-month follow-up, patients who had remained in treatment longer
had fewer drug problems, a smaller proportion of positive urine drug screening
tests, a better employment status, and fewer psychological problems compared with
patients who left treatment earlier. Patients who remained in treatment were also
more likely to be attending self-help meetings, continuing in outpatient
treatment, or attending school. However, for the 447 patients randomly assigned
to the three conditions, there were no significant differences between treatment
modalities on any of the variables at nine-month follow-up. The new intensive
treatment program was not shown to be superior to more traditional treatment
programs.
PMID- 9634158
TI - Prevalence of physical illness among psychiatric inpatients who die of natural
causes.
AB - OBJECTIVE: The state psychiatric hospital is experiencing an increase in
medically sick and aging patients who die of natural causes while hospitalized.
This study explored the "medicalization" of the state hospital by examining the
prevalence of medical illness and its relationship with psychiatric illness and
age among state hospital psychiatric inpatients who died of natural causes-
deaths that were not accidents, homicides, or suicides. METHODS: A total of 179
inpatients who died of natural causes at Western State Hospital in Washington
State between 1989 and 1994 were studied retrospectively through case file
review. Their demographic and institutional characteristics and psychiatric
diagnoses were compared with those of others treated at the hospital (N=9,258).
The medical diagnoses of patients who died were analyzed by age and psychiatric
condition. RESULTS: The patients who died were much older than the other patients
treated during the study period. Two-thirds of those who died had organic mental
disorders, mostly dementia, whereas only a fifth of the other patients had these
disorders. The patients who died had a mean of eight physical illnesses, with a
range from none to 21. Circulatory and respiratory conditions were most
prevalent, affecting half to two-thirds of patients; these conditions had high
rates of comorbidity with organic mental disorders. CONCLUSIONS: The
characteristics of the state hospital population and the services provided are
shifting in response to mental health reform and new policies on patient self
determination. Increased emphasis on medical care added to traditional
psychiatric services will require increased financial and personnel resources.
PMID- 9634159
TI - Assessing the quality of psychiatric hospital care: a German approach.
AB - OBJECTIVE: The German Ministry of Health commissioned a nonprofit organization to
develop a tool for assessing the quality of psychiatric hospital care. METHODS:
The authors were members of an expert group established to develop an assessment
tool that could be used by professional caregivers, patients, patients'
relatives, managers, purchasers, and mental health care planners. RESULTS: A
three-dimensional model was developed in which 23 quality standards may be
applied to 28 areas of practice. For each application, questions can be asked at
four levels to stimulate ongoing quality management: the individual treatment
process, the individual outcome, the treatment unit, and the hospital as a whole.
The authors provide sample questions to illustrate the approach. CONCLUSIONS: The
approach to quality assessment embodied in the model is comprehensive and
addresses ethical issues, but it is also complicated and difficult to handle.
Unlike models developed in the United States, it is not intended to be objective
or standardized, and it does not yield a score. To some extent, the model's
approach to assessment may reflect German cultural values and traditions.
PMID- 9634160
TI - The effects of animal-assisted therapy on anxiety ratings of hospitalized
psychiatric patients.
AB - OBJECTIVE: Animal-assisted therapy involves interaction between patients and a
trained animal, along with its human owner or handler, with the aim of
facilitating patients' progress toward therapeutic goals. This study examined
whether a session of animal-assisted therapy reduced the anxiety levels of
hospitalized psychiatric patients and whether any differences in reductions in
anxiety were associated with patients' diagnoses. METHODS: Study subjects were
230 patients referred for therapeutic recreation sessions. A pre- and
posttreatment crossover study design was used to compare the effects of a single
animal-assisted therapy session with those of a single regularly scheduled
therapeutic recreation session. Before and after participating in the two types
of sessions, subjects completed the state scale of the State-Trait Anxiety
Inventory, a self-report measure of anxiety currently felt. A mixed-models
repeated-measures analysis was used to test differences in scores from before and
after the two types of sessions. RESULTS: Statistically significant reductions in
anxiety scores were found after the animal-assisted therapy session for patients
with psychotic disorders, mood disorders, and other disorders, and after the
therapeutic recreation session for patients with mood disorders. No statistically
significant differences in reduction of anxiety were found between the two types
of sessions. CONCLUSIONS: Animal-assisted therapy was associated with reduced
state anxiety levels for hospitalized patients with a variety of psychiatric
diagnoses, while a routine therapeutic recreation session was associated with
reduced levels only for patients with mood disorders.
PMID- 9634161
TI - Outcome for people with schizophrenia before and after Medicaid capitation at a
community agency in Colorado.
AB - OBJECTIVE: To investigate the effect of a capitated funding mechanism for the
psychiatric care of Medicaid recipients, a study of outcome, satisfaction, and
service utilization among adults with schizophrenia and schizoaffective disorder
was conducted at a Colorado agency before and after the introduction of the new
funding mechanism. METHODS: Two random samples of 100 clients each were selected,
one a year before capitation was introduced and one a year after. Subjects were
interviewed about their quality of life, needs, and service satisfaction.
Psychopathology and service utilization were also measured. RESULTS:
Psychopathology was lower after capitation in most dimensions. The number of
subjects admitted to the hospital during a six-month period beginning a year
after capitation was 57 percent lower than in the equivalent period before
capitation, with no increase in the amount of outpatient treatment provided.
Subjects reported improved quality of life in the domains of work, finances, and
social relations. Significant changes in needs or service satisfaction were not
detected. CONCLUSIONS: No evidence was found that Medicaid capitation had an
adverse effect on the client population after one year. Findings suggested that
capitation led to an efficient use of treatment resources.
PMID- 9634162
TI - Cost-effectiveness of television, radio, and print media programs for public
mental health education.
AB - Mass media campaigns to influence public attitudes and behaviors in the area of
mental health must consider cost-effectiveness, which is based on actual costs,
the number of people reached (exposures), and the impact of the program on the
individual. Cost per exposure is a critical factor. The authors review their
experience in developing media programs in several broadcast formats and in
print. Their experience suggests that an effective television production has a
very high per-exposure cost and that radio is a more cost-effective way to
present health messages. Radio programs also have the advantage of reaching
people in their homes or cars or at work. Brief segments may be particularly cost
effective because they can be can be inserted between programs during prime-time
hours. Print media--newspapers, magazines, and newsletters--can be cost-effective
if magazine or newspaper space is free, but newsletters can be costly due to
fixed postage costs. One advantage of print is that it can be reread, clipped
out, copied, and passed on.
PMID- 9634163
TI - Treatment of inhalant-induced psychotic disorder with carbamazepine versus
haloperidol.
AB - OBJECTIVE: The efficacy and adverse effects of carbamazepine and haloperidol were
compared in the treatment of inhalant-induced psychotic disorder. METHODS: Forty
male patients admitted to an acute psychiatric unit for treatment of inhalant
dependence and inhalant-induced organic mental disorder, as diagnosed by DSM-III
R, were randomly assigned to receive five weeks of treatment with carbamazepine
or haloperidol in identical-appearing capsules. The Brief Psychiatric Rating
Scale and the DiMascio Extrapyramidal Symptoms Scale were administered weekly.
RESULTS: Both treatment groups improved significantly over time. A reduction of
symptom severity of 48.3 percent in the carbamazepine group and 52.7 percent in
the haloperidol group was observed. Approximately half the patients in each group
were considered treatment responders at the end of the study. Adverse effects
were significantly more common and more severe in the haloperidol group.
CONCLUSIONS: Carbamazepine appears to have comparable efficacy but fewer adverse
effects than haloperidol for the treatment of inhalant-induced psychotic
disorder.
PMID- 9634164
TI - Content and curriculum in psychoeducation groups for families of persons with
severe mental illness.
AB - OBJECTIVE: The study compared problems identified by participants in a workshop
for families with a relative who had severe mental illness with topics addressed
in published descriptions of multifamily psychoeducational interventions to
determine whether the problems and needs of family members differed from those
covered in professionally prepared psychoeducational materials. METHODS:
Participants in a one-day psychoeducational workshop were asked to identify and
rank in order of importance the problems they faced in managing mental illness.
Most workshop participants were family members who did not have a severe mental
illness, but family members with a severe mental illness and mental health
service providers also attended. Lists of problems generated by 86 participants
containing a total of 355 items were analyzed for content, and 11 problem
categories were identified and ranked. These categories were then compared with
the content of multifamily psychoeducation programs described in the literature.
RESULTS: Although the methodology limited generalizability of findings, the
results suggest important distinctions between content developed by professionals
and the needs identified by family members, particularly in families' greater
emphasis on negative symptoms and on family relationships. CONCLUSIONS: The
findings suggest that input from the family, the ill family member, and mental
health providers is necessary for developing psychoeducation curricula that will
meet families' needs. Professionals who design multifamily psychoeducation
curricula are encouraged to incorporate enough flexibility to accommodate the
specific needs of members of particular groups and to provide general information
that is useful for all groups.
PMID- 9634165
TI - HIV-related risk behaviors among psychiatric inpatients in India.
AB - The study explored patterns of risk behavior and knowledge about HIV and AIDS
among patients in an inpatient psychiatric facility in south India. Fifty-nine
consecutive patients admitted to a state psychiatric hospital were interviewed
using a semistructured questionnaire. Fifty-one percent had a history of recent
risk behavior, and 86 percent had inadequate knowledge about AIDS. The most
common high-risk behavior was unprotected heterosexual intercourse with a high
risk partner. There was no correlation between knowledge and high-risk behavior.
The findings underscore the need to specifically tailor intervention programs.
PMID- 9634166
TI - A comparison of psychotic and nonpsychotic substance users in the psychiatric
emergency room.
AB - Current illicit drug and alcohol users were identified by laboratory evaluation
of urine samples from nonpsychotic patients without a primary clinical diagnosis
of a substance use disorder seen in a psychiatric emergency room. Urine screens
revealed that 32 of 93 nonpsychotic patients (34 percent) had used a substance
just before visiting the emergency room. Compared with nonusers, users were more
often Caucasian females with adjustment disorders who admitted their previous
substance use. The prevalence of concurrent use among nonpsychotic patients was
higher than among psychotic patients. Nonpsychotic and psychotic users differed
in gender, marital status, level of suicidality, self-report of use, the
clinician's suspicion of use, use of seclusion during the visit, admitting
status, level of care, and disposition.
PMID- 9634167
TI - Cost-effectiveness of clozapine therapy for severe psychosis.
AB - The cost-effectiveness of using the atypical antipsychotic medication clozapine
for severe psychosis was examined in a rural public-sector community mental
health setting in Virginia. Based on a sample of 20 patients, use of clozapine
resulted in estimated cost savings of between $3,000 and $9,000 per patient per
year, including the costs of dropouts from treatment. Savings were mainly due to
a decline in hospitalization from 47.7+/-59.8 days per patient in the year before
clozapine treatment to 4.6+/-11.3 days in the year after. Although this study had
methodological limitations, the results suggest that clozapine may be cost
effective in this setting.
PMID- 9634168
TI - Outcomes of ultrarapid opiate detoxification combined with naltrexone maintenance
and counseling.
AB - Combining naltrexone and clonidine under general anesthesia is being used to
shorten opiate detoxification. This study determined the one-year relapse rate of
persons detoxified using this ultrarapid method in conjunction with naltrexone
maintenance and counseling. Structured telephone interviews were held with 83 out
of a random sample of 113 male patients who were detoxified via the ultrarapid
method more than one year before the interview (average 1.5 years) and their
significant others. Relapse was defined as at least two weeks of daily opiate
use. According to patients and significant others, 57 percent of patients had not
relapsed. This rate is better than rates obtained in studies of other
detoxification methods.
PMID- 9634169
TI - Efficacy vs. effectiveness in psychiatric research.
PMID- 9634170
TI - Dealing with illiteracy.
PMID- 9634171
TI - Interindividual variability in body composition and resting oxygen consumption
rate in breeding tree swallows, Tachycineta bicolor.
AB - Basal metabolic rate is one of the most widely measured physiological traits.
Previous studies on lab mice and field-caught lizards suggest that individuals
with relatively high basal metabolic rates or standard metabolic rates have
relatively large masses of metabolically active tissues (e.g., heart, kidney,
liver). As these are energetically expensive organs, there may be variability
between breeding seasons dependent on, for example, availability of prey and
capacity for energy intake. We present data from breeding tree swallows
(Tachycineta bicolor) collected over two successive seasons. There was no
difference between years in resting oxygen consumption rates, although there were
significant interannual differences in the masses of all organs and tissues
except the pectoralis. Interindividual differences in the masses of the kidney
and small intestine explained 21% of the variation in oxygen consumption rates.
Although individuals with relatively high resting oxygen consumption rates had
relatively large, metabolically active kidneys, they had relatively small
intestines and pectoral muscles. This is in contrast to all previous studies on
mammals and to the single interspecific study of birds. Oxygen consumption rate
also correlated positively with hematocrit. Our results suggest that assumptions
of consistent positive relationships between resting oxygen consumption rate and
organ masses cannot be extended intraspecifically for birds.
PMID- 9634172
TI - Behavior and muscle performance in heterothermic bats.
AB - Body temperatures of winter-resident Korean bats typically range from 10 degrees
to 40 degrees C between August and September and from 3 degrees to 15 degrees C
between January and April. To learn how behavior and the motor systems of
heterothermic bats respond to this body-temperature variation, we examined whole
organism performance and the temperature-dependence of contractile properties of
flight muscle in Murina leucogaster ognevi. In winter and midspring, the lowest
limits of body temperature were 8 degrees C for biting and crawling, 16 degrees C
for visually observable shivering, 22 degrees C for wing flapping (without
powered flight), and 28 degrees C for aerial flight. In summer, the lowest
temperature limits changed little for biting and wing flapping, but the
temperature limits increased about 3 degrees C for crawling, shivering, and
flight. Maximum isometric tetanic tension of the isolated biceps brachii muscle
was almost insensitive to tissue temperatures between 10 degrees and 40 degrees
C, with an average temperature coefficient of 1.02 in summer and of 0.96 in
winter. Rate of tetanic tension production between 10 degrees and 40 degrees C
and shortening velocity and power between 15 degrees and 25 degrees C were
temperature sensitive, with average temperature coefficients of 1.3-2.3. Seasonal
differences in contractile properties within each temperature were not
significant, except for maximum tetanic tension at 30 degrees - 40 degrees C.
Thus, the motor system of the bats had functional capacity over the range of body
temperature experienced in winter to summer. The temperature-dependence of
behavior was consistent with muscle physiology. The defensive behaviors, like
biting and crawling, observed at 8 degrees - 12 degrees C body temperature could
be exerted by using temperature-independent tetanic tension, whereas activities,
such as flight, that require power generation would be restricted to higher body
temperatures by temperature-sensitive rate properties. Some rate processes
appeared to be more temperature sensitive in summer than in winter.
PMID- 9634173
TI - The effects of environmental temperature, hypoxia, and hypercapnia on the
breathing pattern of saltwater crocodiles (Crocodylus porosus).
AB - This study aimed to describe the effects of change in environmental temperature,
hypoxia, and hypercapnia on the breathing pattern of Crocodylus porosus.
Increased environmental temperature, hypoxia, and hypercapnia each caused an
increase in minute ventilation and changes in breathing pattern. Breathing
frequency increased and the duration of the nonventilatory period decreased in
response to all three conditions. Under hypercapnia tidal volume also increased,
with no change in rate of inspiration. The number of breaths per breathing burst
decreased with increased temperature but remained unaltered under hypoxia.
Hypercapnia reduced the number of breaths per burst at 20 degrees C, but the
number did not decrease further at 30 degrees C. The results support the idea
that the responses to increased temperature, hypoxia, and hypercapnia are under
separate control but that some effects of hypercapnia and temperature may involve
a common regulatory pathway.
PMID- 9634174
TI - Performance limits of low-temperature, continuous locomotion are exceeded when
locomotion is intermittent in the ghost crab.
AB - Since a decline in temperature decreases aerobic capacity and slows the kinetics
of exercise-to-rest transitions in ectotherms, we manipulated body temperature to
better understand the performance limits of intermittent locomotion. Distance
capacity (i.e., the total distance traveled before fatigue) of the ghost crab,
Ocypode quadrata, was determined during acute exposure to 15 degrees C inside a
treadmill-respirometer. Instead of exacerbating the near-paralyzing effects of
low body temperature resulting from the frequent transitions, intermittent
locomotion allowed animals to exceed the performance limits measured during
steady-state locomotion. At low temperature, distance capacity for continuous
locomotion at 0.04 m s(-1) (83% maximum aerobic speed) was 60 m. When 30 s of
exercise at 0.08 m s(-1) (166% maximum aerobic speed) was alternated with 30 s of
rest, distance capacity increased to 271 m, 4.5-fold greater than continuous
locomotion at the same average speed (83% maximum aerobic speed). A 30-s pause
following a 30-s exercise period was sufficient for maintaining low lactate
concentrations in muscle and for partial resynthesis of arginine phosphate. A
greater dependency on nonoxidative metabolism due to slowed oxygen uptake
kinetics at low temperature resulted in a decreased duration of the critical
exercise period, which increased performance relative to that measured at higher
temperatures (30 s at 15 degrees C vs. 120 s at 24 degrees C). Despite the ghost
crab's limited aerobic capacity at 15 degrees C, distance capacity during
intermittent locomotion at low temperature can be comparable to that of a crab
moving continuously at a body temperature 10 degrees C warmer. While endurance
capacity is generally correlated with maximum aerobic speed, we have demonstrated
that both locomotor behavior and body temperature must be considered when
characterizing performance limits.
PMID- 9634175
TI - Glucose, lactate, and beta-hydroxybutyrate utilization by rainbow trout brain:
changes during food deprivation.
AB - In order to evaluate the normal (fed conditions) substrate utilization rates of
rainbow trout (Oncorhynchus mykiss) brain, CO2 production from glucose, lactate,
and beta-hydroxybutyrate was tested in pooled brains. Oxidation rates, as well as
the capacity for metabolism of carbohydrate and ketone bodies, were also
evaluated in brain of rainbow trout that were food-deprived for 14 d. Under
normal (fed) conditions, rainbow trout brain oxidized glucose and lactate at
rates higher than those described for mammals; oxidation rates of beta
hydroxybutyrate were lower in rainbow trout brain than those observed for lactate
and glucose, and also lower than those described for mammals. Under food
deprivation conditions, glucose and lactate oxidation rates decreased in brains,
suggesting the existence of brain metabolic depression, and beta-hydroxybutyrate
oxidation rates sharply increased, suggesting increased utilization of ketone
bodies.
PMID- 9634176
TI - Carbon release from purified chemoautotrophic bacterial symbionts of the
hydrothermal vent tubeworm Riftia pachyptila.
AB - The gutless hydrothermal tubeworm Riftia pachyptila Jones relies mainly on its
chemoautotrophic bacterial symbionts to supply nutrients in the form of secreted
organic compounds resulting from fixation and incorporation of CO2. In this
study, symbionts were purified, tested for viability, and incubated in the
presence of labeled CO2. We demonstrated that purified symbionts can be used as a
viable alternative to experiments with bacterial cultures. Several organic acids,
sugars, and amino acids were labeled, but their fraction of the total label
stayed generally constant during the incubation times used. However, increasing
fractions of succinate and, to a lesser degree, glutamate were excreted into the
incubation medium, indicating that these are probably the main carbon-containing
compounds transferred from the symbionts to the host. Glutamate could also
account for the transport of nitrogen from the symbionts to the host.
PMID- 9634177
TI - Daily and seasonal rhythms in selected body temperatures in the Australian lizard
Tiliqua rugosa (Scincidae): field and laboratory observations.
AB - This study examined daily and seasonal activity and thermoregulatory behaviour of
the sleepy lizard, Tiliqua rugosa, a large, diurnally active temperate-dwelling
Australian lizard, in the field and laboratory. Activity temperatures in the
field were compared with those selected by lizards in laboratory thermal
gradients in order to assess the extent to which endogenous versus exogenous
factors contribute to seasonal variations in thermoregulatory behaviour. In the
field, lizards are most active in late winter-spring (August-November), during
which their activity varies from mostly unimodal on days of mild temperature to
bimodal on hot days. In late spring-summer (November-January), activity is
largely restricted to early morning, and at all other seasons sleepy lizards are
rarely active. The winter-spring activity of sleepy lizards is constrained by low
environmental temperatures, as lizards at these seasons have low body
temperatures in the field but higher temperatures in laboratory thermal
gradients. The lower temperatures selected in the laboratory in the summer-autumn
months suggest the avoidance of high ambient temperatures and general inactivity
in the field at these times. Thermal selection in the laboratory at the eight
times of year tested showed that the phase of the minimum and maximum temperature
selected and the amplitude of the rhythm of temperature selected varied
continuously with the time of year. These daily and seasonal shifts in
thermoregulatory behaviour may be regulated by endogenous physiological
mechanisms coupled with seasonal ecological constraints such as food
availability.
PMID- 9634178
TI - Limits to milk flow and energy allocation during lactation of the hispid cotton
rat (Sigmodon hispidus).
AB - Energy allocation for maternal maintenance and milk production was examined in
lactating hispid cotton rats (Sigmodon hispidus) supporting three to seven
offspring at 10 degrees or 24 degrees C. Lactating mothers obtained most of their
energy from dietary intake (ca. 90%), and the remainder was withdrawn from
maternal stores. There was no indication that a central limit to maternal energy
assimilation constrained lactational performance. Maternal energy assimilation
increased with a larger litter size (a higher production cost) and a decline in
ambient temperature (a higher thermoregulatory cost) during lactation, without
reaching an apparent limit. Further, there was no evidence of competitive energy
allocation, which might occur if maternal energy assimilation were limited.
Hence, increases in maternal thermoregulatory expenditure during lactation did
not decrease the energy allocation for milk production. Lactating mothers had a
capacity to increase milk production. Nonetheless, the milk flow did not fully
satisfy the energy requirements of dependent offspring in larger litters or at
the lower ambient temperature (growth rates of offspring declined in both cases).
Local physiological constraints and behavioral effects appear to limit maternal
allocation during lactation. Constraints to allocation may be favored by
selection because they reduce maternal risk or reproductive cost.
PMID- 9634179
TI - Effects of ambient temperature, diet quality, and food restriction on body
composition dynamics of the prairie vole, Microtus ochrogaster.
AB - We manipulated diet quality, food availability, and ambient temperature to
investigate the role of these variables in fat deposition by growing prairie
voles (Microtus ochrogaster) and fat use by adult voles. Exposure to either 5
degrees C or a high-fiber diet reduced fat deposition by growing voles and also
reduced growth as measured by body length. Adult voles on the high-fiber diet
reduced fat content, but exposure to 5 degrees C had no effect on body
composition. Both the high-fiber diet and exposure to 5 degrees C caused
increased food intake and reduced diet digestibility for adult voles. Restricting
access to food resulted in reduced lipid mass of all adult voles and reduced fat
free mass of those held at 5 degrees C. When faced with poor food quality or cold
ambient temperature, voles will increase food intake rather than catabolize lipid
tissue. When food availability is limited, however, voles will use fat stores to
meet the balance of their energy requirements.
PMID- 9634180
TI - Estimation of total body water in pinnipeds using hydrogen-isotope dilution.
PMID- 9634181
TI - Low-field magnetic resonance imaging of early subchondral cyst-like lesions in
induced cranial cruciate ligament deficient dogs.
AB - Six healthy adult male mongrel dogs underwent cranial cruciate ligament
transection in the left stifle. Survey radiography of both stifles and low-field
(0.064 T) MRI of the left stifle were performed preoperatively and at 2, 6, and
12 weeks postoperatively. Focal changes in signal intensity were seen with MRI in
the subchondral bone of the medial tibial condyle at 2 and 6 weeks
postoperatively. At 12 weeks postoperative, a cyst-like lesion was detected using
MRI in the subchondral bone of the medial tibial condyle in 4 of 6 dogs and a
less defined lesion at this site in the remaining 2 dogs. The cyst-like lesion
was spherical in shape and showed typical characteristics of fluid with low
signal intensity on T1-weighted images, high signal intensity on T2-weighted
images and high signal intensity on inversion recovery images. The lesion was
seen in the subchondral bone of the caudal medial and/or middle region of the
tibial plateau slightly cranial to the insertion of the caudal cruciate ligament.
No subchondral cysts were seen in the tibia on radiographs. Histopathologically,
the tibia was characterized by a loose myxomatous phase of early subchondral cyst
formation.
PMID- 9634182
TI - Contrast radiography of the lower urinary tract in the management of obstructive
urolithiasis in small ruminants and swine.
AB - Contrast radiographic visualization of the small ruminant and porcine lower
urinary tract is an infrequently used modality for the evaluation and management
of obstructive urolithiasis. The administration of contrast medium through a tube
cystostomy catheter used to divert urine flow until the resolution of the
obstruction may provide an easy method to evaluate the status of the urethral
obstruction. Contrast fluoroscopy is utilized to monitor and visualize
therapeutic flushing of the urethra. A review of 26 patients seen at the
Veterinary Medical Teaching Hospital suggested that among the radiographic
techniques used, positive contrast normograde cystourethrography through the tube
cystostomy catheter allowed the best visualization of the lower urinary tract
structures and enabled assessment of the resolution of the obstructive lesion.
PMID- 9634183
TI - Radiographic diagnosis--granulomatous pneumonia with intralesional acid-fast
bacilli in an Amazon parrot (Amazona aestiva).
PMID- 9634184
TI - Developmental change of lateral ventricular volume and ratio in Beagle-type dogs
up to 7 months of age.
AB - Eighteen healthy Beagle-type dogs were studied using magnetic resonance (MR)
imaging from a few days after birth up to 7 months of age. We evaluated the onset
of lateral ventricular expansion, the developmental change of lateral ventricular
volume and the ratio of the largest to the smallest lateral ventricular volume.
The onset of lateral ventricular expansion was defined as the day that the
expansion by cerebrospinal fluid (CSF) was first visible in unilateral or
bilateral lateral ventricles on the transverse images at the level of the
intraventricular foramen. It was found that the expansion of lateral ventricles
were first detectable at 3-4 weeks. Lateral ventricular volume ratio varied most
from the onset of lateral ventricular expansion to 75 days of age and stabilized
after that, although absolute brain and lateral ventricular volumes continued to
increase.
PMID- 9634185
TI - Radiographic diagnosis--gastroesophageal intussusception in a cat.
PMID- 9634186
TI - Hydrothorax secondary to a perinephric pseudocyst in a cat.
AB - Hydrothorax was identified in a 14-year-old Siamese cat with a pre-existent
perinephric pseudocyst. The pleural fluid was classified as a low-protein
transudate. Intrapseudocystic scintigraphy confirmed a direct communication
between the pseudocyst and the pleural space. The hydrothorax resolved following
pseudocystectomy and unilateral nephrectomy, demonstrating that the pseudocyst
caused the hydrothorax.
PMID- 9634187
TI - Transesophageal ultrasonography of the normal canine mediastinum.
AB - The mediastinum of eight normal research dogs was examined by transesophageal
ultrasonography with a 5 MHz frequency transducer to establish a baseline for
future use of this new imaging modality as a diagnostic tool. Each examination
consisted of 360 degree scans in both transverse and sagittal planes from the
thoracic inlet to the esophageal hiatus. Dissections of four of these research
dogs were then performed to confirm transesophageal ultrasonography findings.
Transesophageal ultrasonography of the mediastinum was a good imaging modality
for the evaluation of the heartbase, the major cranial mediastinal vessels, the
descending aorta, and occasionally part of the azygos vein. Anatomic orientation
was best obtained by beginning the examination at the heart base. Lymph nodes and
smaller caliber vessels could not be distinguished from surrounding tissues;
however, Doppler ultrasound was useful for identifying the smaller vessels.
Although a 5 MHz frequency transducer is preferred for transesophageal
echocardiography, a higher frequency transducer would improve the resolution of
the images of small near-field structures and may be more appropriate for
mediastinal imaging.
PMID- 9634188
TI - Prevalence of gallbladder sludge in dogs as assessed by ultrasonography.
AB - Ultrasonography of the gallbladder was performed in 3 groups of dogs: 30
clinically healthy dogs, 50 dogs with hepatobiliary disease, and 50 dogs with
diseases other than hepatobiliary disease. The gallbladder was evaluated for the
presence of sludge (echogenic material without acoustic shadowing). Maximal
gallbladder length, width, height, and area were measured as well as the
gallbladder wall thickness. The relative sludge area was calculated as the ratio
of sludge area over gallbladder area on longitudinal images. No significant
difference was found in the prevalence of gallbladder sludge among healthy dogs
(53%), dogs with hepatobiliary diseases (62%), and dogs with other diseases
(48%). The mean age of dogs with sludge was higher than the mean age of dogs
without sludge in dogs with hepatobiliary disease and dogs with other diseases (p
< 0.05). The mean relative sludge area did not differ significantly among the 3
groups. A trend to larger gallbladder dimensions in dogs with sludge compared to
dogs without sludge was detected within the 3 groups. The gallbladder wall
thickness was not different between dogs with and without sludge within the 3
groups. However, the gallbladder wall was more frequently isoechoic than
hyperechoic to the liver in dogs with sludge than in dogs without sludge. The
results of this study indicate that gallbladder sludge, in dogs, is not
particularly associated with hepatobiliary disease and should be considered an
incidental finding.
PMID- 9634189
TI - Ultrasonographic evaluation of the prostate in healthy intact dogs.
AB - Sagittal and transverse ultrasonographic images of the prostate gland were
obtained in 100 healthy adult intact male dogs. Prostatic length, width, and
height on transverse and sagittal images as well as the presence of prostatic
cysts were determined. Linear regression and correlation analysis were performed
between prostatic parameters (length, width, height on sagittal and transverse
images, and estimated volume) and parameters related to body size (body weight,
body height, left kidney length and aortic diameter) and age of the dogs.
Significant positive correlations were found between all prostatic parameters and
parameters related to body size and age. Maximum predicted values for prostatic
parameters for a given body weight and age were determined based on the upper
limit of the 95% confidence interval of the mean predicted values. Such values
should represent a useful tool for ultrasonographic evaluation of the prostate in
the dog. Prostatic cysts were found in 14% of the dogs.
PMID- 9634190
TI - Ultrasonographic findings in 14 dogs with ectopic ureter.
AB - To evaluate ultrasonography as an alternative to contrast radiography for
diagnosis of ectopic ureter in dogs, ultrasonography of the urinary tract was
performed prospectively in a series of urinary incontinent dogs anesthetized for
contrast radiography. Fourteen dogs had ectopic ureter based on surgical,
necropsy or unequivocal contrast radiographic findings. There were eight females
and six males of a variety of breeds; five were Labrador retrievers. Mean (range)
age at the time of diagnosis was 1.2 (0.2-4) years for females and 3.5 (0.3-5)
for males (p < 0.05). Ectopic ureters were unilateral in five dogs (2 left; 3
right) and bilateral in nine dogs. Both ultrasound images and contrast
radiographs were positive for 21 (91%) ectopic ureters; the same two ectopic
ureters were not detected using either modality. The termination of each of the
five normal ureters was visible on ultrasound images; two (40%) were visible on
radiographs. Other ultrasonographic findings included dilatation of the ectopic
ureter and/or ipsilateral renal pelvis in ten (43%) instances, evidence of
pyelonephritis in two dogs (with enlargement of the contralateral kidney in one
dog), and urethral diverticuli in one dog. Ultrasonography is a practical
diagnostic test for ectopic ureter in dogs. In this series there was close
correlation between the ultrasonographic and contrast radiographic findings for
each ectopic ureter, but ultrasonography enabled more accurate determination of
normal ureteral anatomy.
PMID- 9634191
TI - Ultrasound corner--attenuation: the clinical utility of subjective sonographic
assessment.
PMID- 9634192
TI - Ultrasonographic appearance of ovarian tumors in 10 dogs.
AB - Signalment, clinical history, physical examination, clinicopathologic,
radiographic and ultrasonographic findings of 10 female dogs with histologically
confirmed ovarian neoplasms were reviewed. Ultrasonographic images and reports
were reviewed for (1) location, size, outer margins, and echogenicity of the
mass(es), (2) presence of free abdominal fluid, (3) evidence of uterine
abnormalities, and (4) signs of metastatic disease. The masses were classified
according to their ultrasonographic pattern in solid, solid with cystic
component, and cystic. The masses were ultrasonographically reported as being of
ovarian origin in eight dogs, and this origin was included in the list of
differentials in the remaining two dogs. When present, abdominal effusions and
uterine abnormalities were diagnosed by means of ultrasound.
PMID- 9634193
TI - Detection of portal blood flow using per-rectal 99mTc-pertechnetate scintigraphy
in normal cats.
AB - This study reports data obtained from per-rectal 99mTc-pertechnetate portal
scintigraphy in normal cats. It examines the effects of chemical restraint and
the methods employed in defining regions of interest (ROIs) on the shunt index
derived from this data. Six normal cats were used for the study; all six were
chemically restrained for imaging using propofol and later four of them were
manually restrained for comparison. Portal blood flow was studied and the mean
shunt index was found to be 5.9% +/- 3.9 when ROIs were operator defined and 9.2%
+/- 4.4 when ROIs were defined using an isocontour program. In cats that were
restrained using propofol and operator defined ROIs, the mean value for the time
between detection of radioactivity in the liver and in the heart was 14 +/- 1
seconds.
PMID- 9634194
TI - Effect of advanced glycosylation end products on the activity of integrins
expressed on U937 cells.
AB - Advanced glycosylation end products (AGEs) are formed both in healthy old persons
and diabetic patients by nonenzymatic glycosylation. However, AGEs are supposed
to be a major factor in the vascular damages associated with diabetes. The aim of
this study was to assess the effect of AGEs on the activity of cell adhesion
molecules expressed on lymphoid cells. Human serum albumin (HSA) was glycosylated
in vitro and used as a specific stimulating agent with U937 cells. The effect of
glc-HSA was evaluated by the method of homotypic adhesion and adhesion to
immunoplate coated with fibronectin. Specific monoclonal antibodies against
integrins and ICAM-1 were applied in these studies. It was shown that glc-HSA
enhanced the homotypic adhesion. The latter was mediaced via beta2-integrins as
the effect was recorded after 15 min. incubation. The homotypic adhesion for the
cells treated with glc-HSA followed the same kinetics as the cells incubated with
phorbol myriastate acetate, which was used as a positive control. An anti-CD18
antibody inhibited the adhesion of U937 cells which indicated that the glc-HSA
had a positive effect on the activity of beta2-integrins. Treatment with glc-HSA
did not interfere with the adhesion of the referent cells to fibronectin coated
plate. Based on these results the conclusion was drawn that the advanced
glycosylation end products have a differential effect on the activity of integrin
subfamilies expressed on cells of monocyte-macrophage origin.
PMID- 9634195
TI - Activated human T-cells bestow T-cell antigens to non-T-cells by intercellular
antigen transfer.
AB - The mechanism of the appearance of T-cell antigens on B-cells, following in vitro
activation of peripheral blood lymphocytes, was analyzed using the following
model: Purified T-cell suspensions were activated by exposure to
phytohemagglutinin (PHA) for 3 days, and then incubated for one hour in the
presence of cells of either Raji or K562 cells. The expression of T-cell antigens
on the cell lines was determined using immunofluorescent F(ab)2 fragments of
monoclonal antibodies (mAbs). Following exposure of the CD19+ Raji cells to
activated T lymphocytes, 87.6% of the CD19+ cells coexpressed CD2. A large
proportion of the CD19+ cells also expressed CD4, CD5, and CD8 antigens. Similar
results were obtained with Raji cells that were prelabeled with calcein AM. In
Raji cells, which were rendered CD5+ following incubation with activated T cells,
only a negligible level of CD5 mRNA was detected with a sensitive RT-PCR
technique, probably attributable to contamination with T cells. K562 cells
incubated with activated T cells acquired CD2 but not the CD4 and CD8 antigens.
Exposure of either Raji or K562 cells to mAb against CD58 inhibited the transfer
of CD2. The present study indicates that following their activation, T-cells gain
the capacity to transfer T-cell antigens to non-T cells and that CD2 and CD58
molecules are involved in this process.
PMID- 9634196
TI - Efficient induction of human CD4+ T cell lines reactive with a self-K-ras-derived
peptide in vitro, using a mAb to CD29.
AB - In recent studies, we analyzed effects of a large series of mAbs submitted to T
cell and adhesion structure sections of 6th International Workshop on Human
Leukocyte Differentiation Antigens, on proliferative responses of a human CD4+ T
cell clone. We found that certain mAbs to CD27, CD28, CD29, CD43 and CD44
markedly restore T cell responsiveness, only in the presence of the natural
peptide ligand at low concentrations and even in the absence IL-2. To set up
efficient strategies for developing T cell lines and clones reactive with self
peptides in vitro, we stimulated PBMC with a K-ras-derived peptide in the
presence of these mAbs and found that: (a) anti-CD29 mAb MAR4 is effective for in
vitro expansion of K-ras (residue 3-20)-reactive T cells from PBMC; (b) indeed,
DR8 (DRB*0802)-restricted and DR51 (DRB5*0102)-restricted CD4+ T cell clones were
established from the T cell lines; (c) MAR4 inhibits anti-CD3-induced apoptosis
of PBMC; and (d) MAR4 is effective in enhancing anti-CD3- and antigen-induced
proliferative responses of PBMC. Therefore, mAb MAR4 increased efficiency in
establishing T cell clones from PBMC, both by suppressing antigen-driven
activation-induced cell death and by enhancing the T cell proliferation, only in
the presence of TCR/CD3-mediated stimulation. Possible application of MAR4 for
establishing self-reactive T cell lines and expanding T cells ex vivo for anti
cancer immunotherapy, is discussed.
PMID- 9634197
TI - The regulation of phenotype and function of human liver CD3+/CD56+ lymphocytes,
and cells that also co-express CD8 by IL-2, IL-12 and anti-CD3 monoclonal
antibody.
AB - The regulation of phenotype and function of human liver infiltrating lymphocytes
(LIL) by in vitro culture with IL-2, IL-12 and anti-CD3 monoclonal antibodies
(mAb) was investigated. The CD3+ LIL which express 50% less CD3 molecules per
cell than peripheral blood T lymphocytes, exhibited a 6-fold reduction in
proliferation when stimulated through the CD3 complex by anti-CD3 mAb. LIL
freshly isolated or cultured in medium did not suppress MLR response, nor were
they cytotoxic. However, treatment of the LIL cells with IL-2, IL-12 and anti-CD3
induced these cells to suppress autologous responding cells in MLR (ca. 70%) and
to kill autologous or allogeneic cells. Low level cytotoxicity could be induced
by cytokines IL-2, IL-12 or anti-CD3 alone. However, the development of optimum
MLR suppression and cytotoxicity induction was dependent upon stimulation of the
LIL cells through the CD3 complex. The co-expression of CD3 and CD56 on LIL was
also up-regulated by anti-CD3 stimulation in the combination of IL-2 and IL-12.
Most of the CD3+/CD56+ cells, also expressed CD8. After the magnetic bead
separation procedure, the cytotoxic activity was found mainly in the
CD3+/CD56+/CD8+ population. These results suggest that CD3+/CD56+/CD8+ cells can
be expanded by stimulation through the TCR/CD3 complex in the presence of IL-2
and IL-12, which results in the suppression of autologous responding cells by a
cytotoxic mechanism. The proliferative response of the CD3+/CD56+/CD8+ population
was enhanced by the induction of CD1 molecules on the stimulating cells, and anti
CD1 mAb were able to block the response in a dose-dependent manner. The
CD3+/CD56+/CD8+ cells were examined for cytokine production by flow cytometry.
Cytokines IL-4, TNF-alpha, and IFN-gamma were produced by 91.7%, 29.2%, and 27.4%
of the cells, respectively.
PMID- 9634198
TI - DR non-B1 mismatches influence allogeneic MLR-induced TH1- or TH2-like cytokine
responses in rhesus monkeys.
AB - Human and nonhuman primates have multiple DR B1 and non-B1 alleles. However, the
role of mismatched DR non-B1 alleles in primary alloimmune responses is not well
understood. Macaques, which share close DNA homologies with human MHC genes and
have a high number of beta-chain genes in the DR subregion, are preeminent
preclinical models for immunologic studies of transplant tolerance and
immunosuppression. In this study, we examined the effect of allogeneic MHC Class
II DRB mismatches in Th1- and Th2-like cytokine responses elicited in one-way MLR
cultures in rhesus macaques. An ELISPOT method was used to estimate cytokine
secretion at the single cell level. Molecular typing for DRB1 and DR non-B1
alleles was performed by a moderate-high resolution PCR-SSP method using a panel
of 55 primer pairs covering 74 DRB alleles and clusters. Of 35 unrelated
combinations, 66% had multiple (> or = 2) allelic MM at DRB1 and DR non-B1 with
no significant correlation between numbers of DRB1 and DR non-B1 mismatches.
Pairs with 1 or 0 MM were assigned to a mono/null MM group to obtain sufficient
numbers for statistical analysis. The pairs differing by multiple vs. mono/null
DRB1 MM showed no significant difference in cytokine prevalence (P = 0.69). In
contrast, high IFN-gamma/ IL4 SFC ratios were noted in pairs with multiple vs.
mono/null DR non-B1 MM (p = 0.0009). IFN-gamma/IL-10 spot forming cell (SFC)
ratios were consistent with IFN-gamma/IL-4 SFC ratios (r = 0.98). Multiple DR non
B1 mismatches showed a trend towards higher MLR proliferative responses, although
the stimulation index did not reflect the dominant cytokine response. These
observations suggest a bias towards Th1-like cytokine production under
allostimulation with multiple DR non-B1 gene products. Further study of the
primary structure of DR non-B1 determinants may be helpful in understanding the
fine molecular mechanisms governing the regulation of cytokine profiles during
allostimulation in primates.
PMID- 9634199
TI - Studies on functional status of circulating lymphocytes in unaffected members
from cancer families.
AB - That the inheritance of mutations in tumor susceptibility genes alone cannot
determine risk for developing cancer is now well accepted. Immune functions have
long been recognized as one of the important risk modifying factors in this
regard. In an attempt to develop a multiparametric approach to identify high risk
individuals from cancer families, we have examined NK cell function in unaffected
members from familial breast cancer families. We have also carried out a parallel
study of T lymphocyte functions in these individuals. Our studies demonstrate a
significantly lower NK cell activity in members from cancer families. T
lymphocyte activity also showed a similar trend, with the unaffected members
demonstrating a notably lowered T lymphocyte function. In addition the data from
patients reveals differential sensitivity of NK and T lymphocyte function to the
disease phenotype. Implications of these observations are discussed.
PMID- 9634200
TI - HLA and complement factors alleles sharing in Italian couples with recurrent
spontaneous abortions.
AB - Recurrent Spontaneous Abortion (RSA) is postulated to be due to several factors
including immunogenetic mechanisms. Many studies have been conducted on the
effect of the MHC region in the reproductive phenomena suggesting an
immunological or genetic involvement in RSA. We studied couples with 3 or more
abortions among a larger group of couples in which female partners were anti
cardiolipin antibodies negative, resulting in a population of 43 couples typed
for HLA-A, B, C, DR, DQ. In 16 of these 43 couples, complement factors C4A, C4B,
and Bf were typed. The data shows a statistically significant increase of C4B*Q0
in RSA patients (N = 32) compared with the control population (N = 44) (pc =
.00147) and also a statistically significant increase of C4B*Q0 sharing in
aborting couples (43.75%) against the expected sharing rate in the control
population (1.86%) (p < .001). Frequency increase of C4B*Q0 allele in aborting
population leads to the hypothesis that an imbalance of complement factors
expression and activity can have detrimental effects on implantation and embryo
survival. Additionally, the significant sharing rate of C4B*Q0 in couples with
RSA could indicate the existence of a gene in linked to this allele predisposing
to RSA and acting in a recessive manner if present in double copies in the fetus.
PMID- 9634201
TI - Phenotype analysis in neurological models of human disease.
PMID- 9634202
TI - Myelin disorders.
PMID- 9634203
TI - Modelling motor neuron degenerative disease.
PMID- 9634204
TI - Genetic modelling of muscular dystrophies.
PMID- 9634205
TI - Transgenic models for Alzheimer's disease.
PMID- 9634206
TI - Amyotrophic lateral sclerosis: current issues in classification, pathogenesis and
molecular pathology.
AB - The classification of amyotrophic lateral sclerosis (ALS) is reconsidered in the
light of developments in the molecular pathogenesis and histopathology of the
condition. A current view is encapsulated in the El Escorial World Federation of
Neurology criteria for the diagnosis of ALS. While intended for research
purposes, use of these criteria for entry into clinical trials may result in the
exclusion of some patient groups with related disorders that are likely to share
aetiological mechanisms but which are not classified as 'definite ALS' or
'probable ALS'. The relationship between ALS and the more restricted motor
disorders of progressive lateral sclerosis and progressive muscular atrophy,
together with cerebral degenerations including ALS-dementia and ALS-related
frontal lobe dementia, are reviewed. The possibility is raised that they all
represent syndromic manifestations of a similar pathogenetic cascade whose
clinical phenotype depends upon the anatomical selectivity of involvement in each
individual. The new evidence regarding the central role of oxidative stress and
abnormal glutamatergic neurotransmission in familial and sporadic ALS seem
applicable across these disorders. New evidence regarding the molecular pathology
of inclusion bodies in these various syndromes, including ubiquitinated
inclusions and hyaline conglomerate inclusions, shows striking similarities
between them. Marked differences in the anatomical distribution of lesions
determine the predominance and type of motor and cognitive features in each
syndrome. This concept of a clinicopathological spectrum is potentially of equal
relevance to other late onset neurodegenerative disorders including multisystem
atrophies, the Lewy body disorders and various manifestations of Alzheimer's
disease. It will gain increasing importance as therapies evolve from the
symptomatic to those directed at underlying pathogenetic events.
PMID- 9634207
TI - HIV-associated brain pathology: a comparative international study.
AB - Little is known about the frequency and variation of HIV-associated brain
pathology in different geographical centres. To assess whether there is an
association between the frequency of disease and demographic factors we examined
the neuropathological findings in four European and two American cities. The
cities included London, Edinburgh, Paris, Budapest, Baltimore and Newark.
Information was collected on a total of 1144 cases. HIV encephalitis was the most
common observation in all the centres. although its frequency varied between them
(P < 0.01). Furthermore, there were significant differences (P < 0.001) between
the various categories of exposure and the frequency of HIV encephalitis in
Edinburgh and other centres. The occurrence of toxoplasmosis, progressive
multifocal leukoencephalolpathy (PML) and cryptococcal infection also differed
between the various centres (P < 0.01). None of the findings was attributable to
age, sex, or ethnic origin, but the introduction of anti-retroviral treatment,
such as Zidovudine, may have been important. Overall, this study highlights
geographical variability and the potential importance for group of exposure and
anti-retroviral medication as factors affecting the development of various HIV
associated brain lesions.
PMID- 9634208
TI - Prion encephalopathy with insertion of octapeptide repeats: the number of repeats
determines the type of cerebellar deposits.
AB - We studied modifications of the molecular layer of the cerebellum in three
patients with octapeptide repeat insertion (OPRI). Two brothers carrying a six
OPRI showed only spongiosis in haematoxylin & eosin preparations (H&E), whereas
immunocytochemical examination (ICC) with an antiprion protein (PrP) antibody
revealed numerous elongated PrP deposits. The third patient from a family with an
eight-OPRI had numerous plaques visible in H&E preparations and had been
diagnosed as Gerstmann-Straussler-Scheinker syndrome. So far, 15 other cases from
seven families and three individual cases with OPRI have undergone
neuropathological examination. Characteristic PrP deposits were seen in six other
cases, two isolated cases with a four- and a seven-OPRI, whereas four cases with
a six-OPRI came from three different families. Such deposits have never been
reported in other cases of prion encephalopathy, without OPRI. Genuine plaques
were observed in five out of the 15 other patients. Interestingly, four had an
eight-OPRI and one a nine-OPRI. Cases with OPRI are prone to develop different
PrP deposits: those only visible on ICC are not to be confused with genuine
plaques visible in H&E preparations. Elongated PrP deposits are present in cases
with a four- to seven-OPRI, whereas plaques are present when there is an eight-
or a nine-OPRI. All these cases should be termed prion encephalopathy with OPRI.
PMID- 9634209
TI - Intracellular pH and chemoresponse to NH4+ in Paramecium.
AB - Paramecium are attracted to ammonium chloride solutions relative to sodium
chloride control solutions, but little is known about the mechanisms by which
attraction is evoked. A known effect of ammonium solutions in other cell types is
an alteration of intracellular pH. We show here that intracellular pH is elevated
upon initial exposure to 5 mM NH4Cl, but appears to decline within 10 minutes,
both in wild type cells and in two mutants which do not show sustained attraction
to NH4Cl using the standard behavioral assay, the T-maze. We also present
quantitative values of swimming parameters that underlie the response to NH4Cl.
PMID- 9634211
TI - Regulation of flagellar length in Chlamydomonas.
AB - The length of eukaryotic cilia and flagella depends on the cell cycle-regulated
assembly and disassembly of at least 9 doublet and 2 central microtubules, their
associated proteins, and the surrounding membrane. In light-synchronized
Chlamydomonas cells, flagella assembled to 10-14 microm in length near the
beginning of the light period and they disassembled prior to cell division,
during the dark period. Flagella on light-synchronized pf18 Chlamydomonas mutants
grew to 10-12 microm near the beginning of the light period but shortened by 50%
or more by the end of the light period. Flagellar length was cell-cycle
regulated: when flagella were amputated at various times during the light period,
new flagella regenerated to the lengths of control cells at that time of the
light cycle. The later in the cycle pf18 cells were deflagellated, the shorter
were the regenerated flagella. Flagellar shortening was not affected, in either
pf18 or wild-type (wt) cells, by inhibitors of protein synthesis or of
microtubule assembly, so flagellar length cannot depend on protein turnover.
Shortening in pf18 was attenuated by Li+, which stimulated flagellar growth in wt
cells, by red light, by protein kinase inhibitors, and by the Ca2+ channel
blockers La3+ and Cd2+. Shortening was increased by cAMP, Na+, K+, and EGTA. Ca2+
CAM blockers did not affect pf18 shortening but they increased shortening in wt
and fa1 cells. We propose that flagellar length is regulated by a signal
transduction pathway that is sensitive to Ca2+ levels and red light.
PMID- 9634210
TI - Changes in the F-actin cytoskeleton during neurosensory bristle development in
Drosophila: the role of singed and forked proteins.
AB - Drosophila neurosensory bristle development provides an excellent model system to
study the role of the actin-based cytoskeleton in polarized cell growth. We used
confocal fluorescence microscopy of isolated thoracic tissue to characterize
changes in F-actin that occurred during macrochaete development in wild type
flies and mutants that have aberrant bristle morphology. At the earliest stages
in wild type bristle development, cortical patches of F-actin were present, but
no bundles were observed. Actin bundles began to form at 31% of pupal development
and became more prominent as development progressed. The F-actin patches
gradually disappeared and were no longer present by 38% of pupal development. The
distribution of F-actin in singed3 mutant macrochaetae was indistinguishable from
wild type bristles until 35% of development when the actin bundles began to splay
and appear ribbon-like. In forked36a bristles, the mutant phenotype was evident
at earlier stages of development than the singed3 mutant. Wild type tissue
stained with antibodies against the forked protein demonstrated that the forked
protein colocalized with F-actin structures found in early and late stage
developing macrochaetae. Antibodies against the singed protein showed it appeared
to localize with F-actin structures only at later stages in development. These
data suggested that the forked gene product was required for the initiation of
fiber bundle formation and the singed gene product was required for the
maintenance of fiber bundle morphology during bristle development. Similar
analyses of singed3/forked36a double mutants provided additional genetic evidence
that the forked gene product was required before the singed gene product.
Further, the analyses suggested that at least one additional crosslinking protein
was present in these bundles.
PMID- 9634212
TI - Visualization of kinetochores and analysis of their refractility in crane-fly
spermatocytes after aldehyde fixation.
AB - Glutaraldehyde and formaldehyde were used to fix crane-fly spermatocytes for
observation with differential interference contrast (DIC) microscopy. In aldehyde
fixed cells, kinetochores exhibit contrast not normally observed in living cells.
Although the mechanism underlying this result is not understood, the
visualization of kinetochores as distinct refractile objects opens the way for
analysis of unstained kinetochores with the light microscope. The analysis of
kinetochore refractility reported in this paper is made possible by the finding
that the refractility of chromosomes in formaldehyde-fixed cells decreases as the
concentration of formaldehyde is increased. In 4% formaldehyde, the refractility
of chromosomes is matched with that of its surround, chromosomes appear
invisible, and kinetochores may be analyzed as if chromosomes were not present.
Kinetochores were imaged with DIC optics, and then digital image analysis was
performed. Gray-level scans through the highlight and shadow of an individual
kinetochore parallel to the axis of shear resulted in a curve having a slope
proportional to the DIC optical path gradient. Curves from autosomal kinetochores
imaged in anaphase had slopes approximately one-half those recorded at metaphase
under identical optical conditions. By contrast, kinetochore thicknesses (defined
as the distance between the peak and the valley of a gray-level scan) at those
two stages were not significantly different. These data suggest a loss of dry
mass from autosomal kinetochores during anaphase. Neither the refractility nor
thickness of lagging sex kinetochores varied as autosomes went through anaphase.
The conclusion drawn from these findings is that the decreased refractility of
autosomal kinetochores in anaphase is movement-related.
PMID- 9634213
TI - Actin-dependent anterograde movement of growth-cone-like structures along growing
hippocampal axons: a novel form of axonal transport?
AB - In time-lapse video recordings of hippocampal neurons in culture, we have
identified previously uncharacterized structures, nicknamed "waves," that exhibit
lamellipodial activity closely resembling that of growth cones, but which
periodically emerge at the base of axons and travel distally at an average rate
of 3 microm/min. In electron micrographs of identified waves, the cortical region
of the axon appears expanded to either side, forming lamellipodia like those at
growth cones. No other gross differences were noted in the ultrastructural
features of the axon shaft at the site of a wave. Immunocytochemistry revealed
that waves contain a marked concentration of F-actin, GAP-43, cortactin, and
ezrin or a related protein, constituents that are also concentrated in growth
cones. Treatment with the actin-disrupting agent cytochalasin B caused a
reversible collapse of lamellipodia and cessation of the forward movement of
individual waves along the axon, indicating that their anterograde transport is
dependent on intact actin filaments. Treatment with the microtubule
depolymerizing agent nocodazole led to a rapid disorganization of wave structure
and a subsequent suppression of wave activity that may reflect a role of
microtubules in actin organization. The results suggest that actin and other
cytoskeletal components concentrated in growth cones may be transported together
as growth-cone-like structures from the cell body to the axon tip via an actin
dependent mechanism.
PMID- 9634214
TI - Rigor-type mutation in the kinesin-related protein HsEg5 changes its subcellular
localization and induces microtubule bundling.
AB - HsEg5 is a human kinesin-related motor protein essential for the formation of a
bipolar mitotic spindle. It interacts with the mitotic centrosomes in a
phosphorylation-dependent manner. To investigate further the mechanisms involved
in targetting HsEg5 to the spindle apparatus, we expressed various mutants of
HsEg5 in HeLa cells. All these mutants share a mutation of Thr-112 in the N
terminal motor domain, resulting in the inactivation of the ATP binding domain.
In vitro, the HsEg5-T112N mutant motor domain showed a nucleotide-independent
microtubule association, typical of a kinesin protein binding to microtubules in
a rigor state. In vivo, overexpression of the HsEg5 rigor mutant in HeLa cells
induced, in interphase, microtubule bundling, and, in mitosis, the formation of
monopolar mitotic spindles similar to those observed after microinjection of anti
HsEg5 antibodies. Localization of the HsEg5 rigor mutant on cytoplasmic
microtubules did not require the C-terminal tail domain but was lost when the
stalk domain was also deleted. Sucrose gradient centrifugation experiments showed
that microtubule bundling was most likely caused by the binding of HsEg5 mutants
in a dimeric state. These results demonstrate that the precise subcellular
localization of HsEg5 in vivo is regulated not only by the phosphorylation of the
tail domain but also by the oligomeric state of the protein.
PMID- 9634215
TI - Altered drug resistance of microtubules in cells exposed to infrared light
pulses: are microtubules the "nerves" of cells?
AB - This article describes the first quantitative assay of the response of an entire
population of cultured mammalian cells to a pulsating near-infrared signal. The
assay measures the change of resistance to nocodazole of reconstituted
cytoplasmic asters of irradiated cells. Using this assay on CV1 cells, I obtained
results suggesting that pulsating near-infrared signals of 1 s pulse length
reduced the stability of the radial microtubules around the centrosome. The
results are consistent with the interpretation that the centrosome responded to
the light by sending signals along its radial array of microtubules whose
stability was then altered. The results may be an example of a more general
function of the centrosome to integrate exogenous signals and send response
signals along microtubules to various sites within the cell.
PMID- 9634216
TI - Pharmacological and genetic evidence for a role of rootlet and phycoplast
microtubules in the positioning and assembly of cleavage furrows in Chlamydomonas
reinhardtii.
AB - In Chlamydomonas reinhardtii, specialized cytoskeletal structures known as
rootlet microtubules are present throughout interphase and mitosis. During
cytokinesis, an array of microtubules termed the phycoplast is nucleated from
rootlet microtubules and forms coincidentally with the cleavage furrow [Johnson
and Porter, 1968: J. Cell Biol. 38:403-425; Holmes and Dutcher, 1989: J. Cell
Sci. 94:273-285; Gaffel and el-Gammel, 1990: Protoplasma 156:139-148; Schibler
and Huang, 1991: J. Cell Biol. 113:605-614]. We have obtained two independent
lines of evidence that support the hypothesis that the rootlet and phycoplast
microtubules play a direct role in cleavage furrow placement and assembly. First,
the destabilization of spindle and phycoplast microtubules by pharmacological
agents was accompanied by the aberrant distribution of actin and a failure of
cytokinesis. Second, we characterized mutant strains that failed to complete
cytokinesis properly. Actin and myosin were mislocalized to additional rootlet
microtubules in the cyt2-1 strain, and this mislocalization was correlated with
the presence of additional cleavage furrows. This evidence suggests that
microtubules are necessary for the correct positioning and assembly of functional
cleavage furrows in C. reinhardtii.
PMID- 9634217
TI - When moderation turns to greed.
PMID- 9634218
TI - Espionage verdict prompts call for retraction of polymerase paper.
PMID- 9634219
TI - NIH 'should help sharing of research tools'.
PMID- 9634220
TI - French researchers reject reform plans...as medical agency agrees to a
compromise.
PMID- 9634221
TI - Harvard's 'oncomouse' fails to win Canadian patent.
PMID- 9634222
TI - Swiss reject curbs on genetic engineering.
PMID- 9634223
TI - British biotech responds to allegations.
PMID- 9634224
TI - Ethical discourse by science-in-fiction.
PMID- 9634225
TI - Blueprint for the white plague.
PMID- 9634226
TI - Evolutionary biology. Help and you shall be helped.
PMID- 9634227
TI - Brain, heart and stress.
PMID- 9634228
TI - Chemokines beyond inflammation.
PMID- 9634229
TI - Sound localization and neurons.
PMID- 9634230
TI - Deciphering the biology of Mycobacterium tuberculosis from the complete genome
sequence.
AB - Countless millions of people have died from tuberculosis, a chronic infectious
disease caused by the tubercle bacillus. The complete genome sequence of the best
characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined
and analysed in order to improve our understanding of the biology of this slow
growing pathogen and to help the conception of new prophylactic and therapeutic
interventions. The genome comprises 4,411,529 base pairs, contains around 4,000
genes, and has a very high guanine + cytosine content that is reflected in the
biased amino-acid content of the proteins. M. tuberculosis differs radically from
other bacteria in that a very large portion of its coding capacity is devoted to
the production of enzymes involved in lipogenesis and lipolysis, and to two new
families of glycine-rich proteins with a repetitive structure that may represent
a source of antigenic variation.
PMID- 9634231
TI - Chemical processing in the coma as the source of cometary HNC.
AB - The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance
(relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar
clouds raised the possibility that these molecules might be surviving
interstellar material. The preservation of material from the Sun's parent
molecular cloud would provide important constraints on the processes that took
place in the protostellar nebula. But another possibility is that HNC is produced
by photochemical processes in the coma, which means that its abundance could not
be used as a direct constraint on conditions in the early Solar System. Here we
show that the HNC/HCN ratio determined for comet Hale-Bopp varied with
heliocentric distance in a way that matches the predictions of models of gas
phase chemical production of HNC in the coma, but cannot be explained if the HNC
molecules were coming from the comet's nucleus. We conclude that HNC forms mainly
by chemical reactions in the coma, and that such reactions need to be considered
when attempting to deduce the composition of the nucleus from observations of the
coma.
PMID- 9634232
TI - Evolution of indirect reciprocity by image scoring.
AB - Darwinian evolution has to provide an explanation for cooperative behaviour.
Theories of cooperation are based on kin selection (dependent on genetic
relatedness), group selection and reciprocal altruism. The idea of reciprocal
altruism usually involves direct reciprocity: repeated encounters between the
same individuals allow for the return of an altruistic act by the recipient. Here
we present a new theoretical framework, which is based on indirect reciprocity
and does not require the same two individuals ever to meet again. Individual
selection can nevertheless favour cooperative strategies directed towards
recipients that have helped others in the past. Cooperation pays because it
confers the image of a valuable community member to the cooperating individual.
We present computer simulations and analytic models that specify the conditions
required for evolutionary stability of indirect reciprocity. We show that the
probability of knowing the 'image' of the recipient must exceed the cost-to
benefit ratio of the altruistic act. We propose that the emergence of indirect
reciprocity was a decisive step for the evolution of human societies.
PMID- 9634233
TI - Selective representation of relevant information by neurons in the primate
prefrontal cortex.
AB - The severe limitation of the capacity of working memory, the ability to store
temporarily and manipulate information, necessitates mechanisms that restrict
access to it. Here we report tests to discover whether the activity of neurons in
the prefrontal (PF) cortex, the putative neural correlate of working memory,
might reflect these mechanisms and preferentially represent behaviourally
relevant information. Monkeys performed a 'delayed-matching-to-sample' task with
an array of three objects. Only one of the objects in the array was relevant for
task performance and the monkeys needed to find that object (the target) and
remember its location. For many PF neurons, activity to physically identical
arrays varied with the target location; the location of the non-target objects
had little or no influence on activity. Information about the target location was
present in activity as early as 140ms after array onset. Also, information about
which object was the target was reflected in the sustained activity of many PF
neurons. These results suggest that the prefrontal cortex is involved in
selecting and maintaining behaviourally relevant information.
PMID- 9634234
TI - Gli/Zic factors pattern the neural plate by defining domains of cell
differentiation.
AB - Three cell types differentiate in the early frog neural plate: neural crest at
the lateral edges, floorplate at the midline and primary neurons in three
bilateral stripes. Floorplate cells and ventral neurons are induced by Sonic
hedgehog (Shh) and neural crest and dorsal neurons are induced by epidermal
factors such as bone morphogenetic proteins (BMPs). Neurogenesis in a subset of
cells within the stripes involves lateral inhibition. However, the process by
which pools of precursors are defined in stereotypic domains in response to
inductive signals is unknown. Here we show that frog Zic2 encodes a zinc-finger
transcription factor of the Gli superfamily which is expressed in stripes that
alternate with those in which primary neurons differentiate and overlap the
domains of floorplate and neural crest progenitors. Zic2 inhibits neurogenesis
and induces neural crest differentiation. Conversely, Gli proteins are widely
expressed, induce neurogenesis and inhibit neural crest differentiation. Zic2 is
therefore a vertebrate pre-pattern gene, encoding anti-neurogenic and crest
inducing functions that counteract the neurogenic but not the floorplate-inducing
activity of Gli proteins. We propose that the combined function of Gli/Zic genes
responds to inductive signals and induces patterned neural cell differentiation.
PMID- 9634235
TI - Molecular identification of a hyperpolarization-activated channel in sea urchin
sperm.
AB - Sea urchin eggs attract sperm through chemotactic peptides, which evoke complex
changes in membrane voltage and in the concentrations of cyclic AMP, cyclic GMP
and Ca2+ ions The intracellular signalling pathways and their cellular targets
are largely unknown. We have now cloned, from sea urchin testis, the
complementary DNA encoding a channel polypeptide, SPIH. Functional expression of
SPIH gives rise to weakly K+-selective hyperpolarization-activated channels,
whose activity is enhanced by the direct action of cAMP. Thus, SPIH is under the
dual control of voltage and cAMP. The SPIH channel, which is confined to the
sperm flagellum, may be involved in the control of flagellar beating. SPIH
currents exhibit all the hallmarks of hyperpolarization-activated currents (Ih),
which participate in the rhythmic firing of central neurons, control pacemaking
in the heart, and curtail saturation by bright light in retinal photoreceptors.
Because of their sequence and functional properties, Ih channels form a class of
their own within the superfamily of voltage-gated and cyclic-nucleotide-gated
channels.
PMID- 9634236
TI - A family of hyperpolarization-activated mammalian cation channels.
AB - Pacemaker activity of spontaneously active neurons and heart cells is controlled
by a depolarizing, mixed Na+/K+ current, named Ih (or I(f) in the sinoatrial node
of the heart). This current is activated on hyperpolarization of the plasma
membrane. In addition to depolarizing pacemaker cells, Ih is involved in
determining the resting membrane potential of neurons and provides a mechanism to
limit hyperpolarizing currents in these cells. Hormones and neurotransmitters
that induce a rise in cyclic AMP levels increase Ih by a mechanism that is
independent of protein phosphorylation, and which involves direct binding of the
cyclic nucleotide to the channel that mediates Ih. Here we report the molecular
cloning and functional expression of the gene encoding a hyperpolarization
activated cation channel (HAC1) that is present in brain and heart. This channel
exhibits the general properties of Ih channels. We have also identified full
length sequences of two related channels, HAC2 and HAC3, that are specifically
expressed in the brain, indicating the existence of a family of hyperpolarization
activated cation channels.
PMID- 9634237
TI - The chemokine receptor CXCR4 is essential for vascularization of the
gastrointestinal tract.
AB - Vascularization of organs generally occurs by remodelling of the preexisting
vascular system during their differentiation and growth to enable them to perform
their specific functions during development. The molecules required by early
vascular systems, many of which are receptor tyrosine kinases and their ligands,
have been defined by analysis of mutant mice. As most of these mice die during
early gestation before many of their organs have developed, the molecules
responsible for vascularization during organogenesis have not been identified.
The cell-surface receptor CXCR4 is a seven-transmembrane-spanning, G-protein
coupled receptor for the CXC chemokine PBSF/SDF-1 (for pre-B-cell growth
stimulating factor/stromal-cell-derived factor), which is responsible for B-cell
lymphopoiesis, bone-marrow myelopoiesis and cardiac ventricular septum formation.
CXCR4 also functions as a co-receptor for T-cell-line tropic human
immunodeficiency virus HIV-1. Here we report that CXCR4 is expressed in
developing vascular endothelial cells, and that mice lacking CXCR4 or PBSF/SDF-1
have defective formation of the large vessels supplying the gastrointestinal
tract. In addition, mice lacking CXCR4 die in utero and are defective in vascular
development, haematopoiesis and cardiogenesis, like mice lacking PBSF/SDF-1,
indicating that CXCR4 is a primary physiological receptor for PBSF/SDF-1. We
conclude that PBSF/SDF-1 and CXCR4 define a new signalling system for organ
vascularization.
PMID- 9634239
TI - Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals.
AB - In female mammals one of the X chromosomes is rendered almost completely
transcriptionally inactive to equalize expression of X-linked genes in males and
females. The inactive X chromosome is distinguished from its active counterpart
by its condensed appearance in interphase nuclei, late replication, altered DNA
methylation, hypoacetylation of histone H4, and by transcription of a large cis
acting nuclear RNA called Xist. Although it is believed that the inactivation
process involves the association of specific protein(s) with the chromatin of the
inactive X, no such proteins have been identified. We discovered a new gene
family encoding a core histone which we called macroH2A (mH2A). The amino
terminal third of mH2A proteins is similar to a full-length histone H2A, but the
remaining two-thirds is unrelated to any known histones. Here we show that an
mH2A1 subtype is preferentially concentrated in the inactive X chromosome of
female mammals. Our results link X inactivation with a major alteration of the
nucleosome, the primary structural unit of chromatin.
PMID- 9634238
TI - Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar
development.
AB - Chemokines and their receptors are important in cell migration during
inflammation, in the establishment of functional lymphoid microenvironments, and
in organogenesis. The chemokine receptor CXCR4 is broadly expressed in cells of
both the immune and the central nervous systems and can mediate migration of
resting leukocytes and haematopoietic progenitors in response to its ligand, SDF
1. CXCR4 is also a major receptor for strains of human immunodeficiency virus-1
(HIV-1) that arise during progression to immunodeficiency and AIDS dementia. Here
we show that mice lacking CXCR4 exhibit haematopoietic and cardiac defects
identical to those of SDF-1-deficient mice, indicating that CXCR4 may be the only
receptor for SDF-1. Furthermore, fetal cerebellar development in mutant animals
is markedly different from that in wild-type animals, with many proliferating
granule cells invading the cerebellar anlage. This is, to our knowledge, the
first demonstration of the involvement of a G-protein-coupled chemokine receptor
in neuronal cell migration and patterning in the central nervous system. These
results may be important for designing strategies to block HIV entry into cells
and for understanding mechanisms of pathogenesis in AIDS dementia.
PMID- 9634240
TI - A piece of my mind. Tribute.
PMID- 9634241
TI - Medical groups say physicians can help keep kids from killing.
PMID- 9634242
TI - Compensation for injured research subjects.
PMID- 9634243
TI - RAID teams to respond to terrorism threat. Rapid assessment and initial
detection.
PMID- 9634244
TI - From the Centers for Disease Control and Prevention. Boat-propeller-related
injuries--Texas, 1997.
PMID- 9634245
TI - From the Centers for Disease Control and Prevention. Nosocomial Ralstonia
pickettii colonization associated with intrinsically contaminated saline solution
-Los Angeles, California, 1998.
PMID- 9634246
TI - From the Centers for Disease Control and Prevention. Corneal decompensation after
intraocular ophthalmic surgery--Missouri, 1998.
PMID- 9634247
TI - From the Centers for Disease Control and Prevention. Pregnancy-related death
associated with heparin and aspirin treatment for infertility, 1996.
PMID- 9634248
TI - What price survival? The future of Blue Cross and Blue Shield.
PMID- 9634249
TI - Rapid opioid detoxification.
PMID- 9634250
TI - Rapid opioid detoxification.
PMID- 9634251
TI - Rapid opioid detoxification.
PMID- 9634252
TI - Risk of fetal anomalies with exposure to selective serotonin reuptake inhibitors.
PMID- 9634253
TI - Risk of fetal anomalies with exposure to selective serotonin reuptake inhibitors.
PMID- 9634254
TI - Use of serotonin reuptake inhibitors by women of childbearing potential.
PMID- 9634255
TI - Antiretroviral therapy and improving AIDS survival.
PMID- 9634256
TI - Space medicine in peer-reviewed journals.
PMID- 9634257
TI - Merck-sponsored simvastatin (Zocor) compliance program for patients using Wal
Mart Pharmacy: of benefit to whom?
PMID- 9634258
TI - Management of pain in elderly patients with cancer. SAGE Study Group. Systematic
Assessment of Geriatric Drug Use via Epidemiology.
AB - CONTEXT: Cancer pain can be relieved with pharmacological agents as indicated by
the World Health Organization (WHO). All too frequently pain management is
reported to be poor. OBJECTIVE: To evaluate the adequacy of pain management in
elderly and minority cancer patients admitted to nursing homes. DESIGN:
Retrospective, cross-sectional study. SETTING: A total of 1492 Medicare-certified
and/or Medicaid-certified nursing homes in 5 states participating in the Health
Care Financing Administration's demonstration project, which evaluated the
implementation of the Resident Assessment Instrument and its Minimum Data Set.
STUDY POPULATION: A group of 13 625 cancer patients aged 65 years and older
discharged from the hospital to any of the facilities from 1992 to 1995. Data
were from the multilinked Systematic Assessment of Geriatric Drug Use via
Epidemiology (SAGE) database. MAIN OUTCOME MEASURES: Prevalence and predictors of
daily pain and of analgesic treatment. Pain assessment was based on patients'
report and was completed by a multidisciplinary team of nursing home personnel
that observed, over a 7-day period, whether each resident complained or showed
evidence of pain daily. RESULTS: A total of 4003 patients (24%, 29%, and 38% of
those aged > or =85 years, 75 to 84 years, and 65 to 74 years, respectively)
reported daily pain. Age, gender, race, marital status, physical function,
depression, and cognitive status were all independently associated with the
presence of pain. Of patients with daily pain, 16% received a WHO level 1 drug,
32% a WHO level 2 drug, and only 26% received morphine. Patients aged 85 years
and older were less likely to receive morphine or other strong opiates
[corrected] than those aged 65 to 74 years (13% vs 38%, respectively). More than
a quarter of patients (26%) in daily pain did not receive any analgesic agent.
Patients older than 85 years in daily pain were also more likely to receive no
analgesia (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.13-1.73). Other
independent predictors of failing to receive any analgesic agent were minority
race (OR, 1.63; 95% CI, 1.18-2.26 for African Americans), low cognitive
performance (OR, 1.23; 95% CI, 1.05-1.44), and the number of other medications
received (OR, 0.65; 95% CI, 0.5-0.84 for 11 or more medications). CONCLUSIONS:
Daily pain is prevalent among nursing home residents with cancer and is often
untreated, particularly among older and minority patients.
PMID- 9634259
TI - Physicians disciplined for sex-related offenses.
AB - CONTEXT: Physicians who abuse their patients sexually cause immense harm, and,
therefore, the discipline of physicians who commit any sex-related offenses is an
important public health issue that should be examined. OBJECTIVES: To determine
the frequency and severity of discipline against physicians who commit sex
related offenses and to describe the characteristics of these physicians. DESIGN
AND SETTING: Analysis of sex-related orders from a national database of
disciplinary orders taken by state medical boards and federal agencies. SUBJECTS:
A total of 761 physicians disciplined for sex-related offenses from 1981 through
1996. MAIN OUTCOME MEASURES: Rate and severity of discipline over time for sex
related offenses and specialty, age, and board certification status of
disciplined physicians. RESULTS: The number of physicians disciplined per year
for sex-related offenses increased from 42 in 1989 to 147 in 1996, and the
proportion of all disciplinary orders that were sex related increased from 2.1%
in 1989 to 4.4% in 1996 (P<.001 for trend). Discipline for sex-related offenses
was significantly more severe (P<.001) than for non-sex-related offenses, with
71.9% of sex-related orders involving revocation, surrender, or suspension of
medical license. Of 761 physicians disciplined, the offenses committed by 567
(75%) involved patients, including sexual intercourse, rape, sexual molestation,
and sexual favors for drugs. As of March 1997, 216 physicians (39.9%) disciplined
for sex-related offenses between 1981 and 1994 were licensed to practice.
Compared with all physicians, physicians disciplined for sex-related offenses
were more likely to practice in the specialties of psychiatry, child psychiatry,
obstetrics and gynecology, and family and general practice (all P<.001) than in
other specialties and were older than the national physician population, but were
no different in terms of board certification status. CONCLUSIONS: Discipline
against physicians for sex-related offenses is increasing over time and is
relatively severe, although few physicians are disciplined for sexual offenses
each year. In addition, a substantial proportion of physicians disciplined for
these offenses are allowed to either continue to practice or return to practice.
PMID- 9634260
TI - Physicians disciplined by a state medical board.
AB - CONTEXT: State medical boards discipline several thousand physicians each year.
Although certain subgroups, such as those disciplined for malpractice, substance
use, or sexual abuse, have been studied, little is known about disciplined
physicians as a group. OBJECTIVE: To assess the offenses, contributing factors,
and type of discipline of a consecutive series of disciplined physicians. DESIGN:
Case-control study on publicly available data matching 375 disciplined physicians
with 2 groups of control physicians, one matched solely by locale, and a second
matched for sex, type of practice, and locale. SUBJECTS: All disciplined
physicians publicly reported by the Medical Board of California from October 1995
through April 1997. MAIN OUTCOME MEASURES: Characteristics of disciplined
physicians, offenses leading to discipline, and type of discipline. RESULTS: A
total of 375 physicians licensed by the Medical Board of California
(approximately 0.24% per year) were disciplined for 465 offenses. The most
frequent causes for discipline were negligence or incompetence (34%), abuse of
alcohol or other drugs (14%), inappropriate prescribing practices (11%),
inappropriate contact with patients (10%), and fraud (9%). Discipline imposed was
revocation of medical license (21%), actual suspension of license (13%), stayed
suspension of license (45%), and reprimand (21%). Type of offense was
significantly associated with severity of discipline (P=.03). In logistic
regression models comparing disciplined physicians with controls matched by
locale, board discipline was significantly associated with physicians' sex (odds
ratio [OR] for women, 0.44; 95% confidence interval [CI], 0.28-0.70) and
involvement in direct patient care (OR, 2.56; 95% CI, 1.75-3.75). In the
regression model with additional matching criteria, disciplinary action was
negatively associated with specialty board certification (OR, 0.42; 95% CI, 0.29
0.60) and positively associated with being in practice more than 20 years (OR,
2.02; 95% CI, 1.39-2.92). CONCLUSIONS: A small but substantial proportion of
physicians is disciplined each year for a variety of offenses. Further study of
disciplined physicians is necessary to identify physicians at high risk for
offenses leading to disciplinary action and to develop effective interventions to
prevent these offenses.
PMID- 9634261
TI - Trends in HIV incidence among young adults in the United States.
AB - CONTEXT: Behaviors that result in potential exposure to human immunodeficiency
virus (HIV) usually begin in adolescence or young adulthood, but trends in HIV
incidence in young people remain unclear. OBJECTIVE: To estimate trends in HIV
incidence in teenagers and young adults. DESIGN AND SETTING: Back-calculation of
past HIV incidence in persons born between 1960 and 1974 using US national
acquired immunodeficiency syndrome (AIDS) incidence data and estimates of the
distribution of times between HIV infection and AIDS. MAIN OUTCOME MEASURES:
Incidence and prevalence of HIV in 1988 and 1993 in persons aged 20 and 25 years,
respectively, in each of those years. RESULTS: As of January 1993, about 22000
men and 11000 women aged 18 to 22 years were living with HIV infection in the
United States. Homosexual contact was the leading route of infection among young
men. Heterosexual contact was the leading route of infection among young women.
The HIV incidence attributed to homosexual contact or injection drug use
decreased among persons aged 20 and 25 years between 1988 and 1993, but HIV
incidence attributed to heterosexual contact was stable or increasing. Notably,
in men aged 20 and 25 years, HIV prevalence declined by about 50% in white men
but was relatively stable in black and Hispanic men. In contrast, HIV prevalence
in women aged 20 and 25 years rose by 36% and 45%, respectively, because of
increasing heterosexual transmission. Overall, HIV prevalence in persons aged 20
and 25 years declined by only 14% between 1988 and 1993. CONCLUSIONS: In young
persons, HIV incidence in homosexual men and injection drug users was slowing by
1993; this favorable trend was offset by increasing heterosexual transmission,
especially in minorities.
PMID- 9634262
TI - Effect of a garlic oil preparation on serum lipoproteins and cholesterol
metabolism: a randomized controlled trial.
AB - CONTEXT: Garlic-containing drugs have been used in the treatment of
hypercholesterolemia even though their efficacy is not generally established.
Little is known about the mechanisms of action of the possible effects on
cholesterol in humans. OBJECTIVE: To estimate the hypocholesterolemic effect of
garlic oil and to investigate the possible mechanism of action. DESIGN: Double
blind, randomized, placebo-controlled trial. SETTING: Outpatient lipid clinic.
PATIENTS: We investigated 25 patients (mean age, 58 years) with moderate
hypercholesterolemia. INTERVENTION: Steam-distilled garlic oil preparation (5 mg
twice a day) vs placebo each for 12 weeks with wash-out periods of 4 weeks. MAIN
OUTCOME MEASURES: Serum lipoprotein concentrations, cholesterol absorption, and
cholesterol synthesis. RESULTS: Baseline lipoprotein profiles were (mean [SD]):
total cholesterol, 7.53 (0.75) mmol/L (291 [29] mg/dL); low-density lipoprotein
cholesterol (LDL-C), 5.35 (0.78) mmol/L (207 [30] mg/dL); high-density
lipoprotein cholesterol (HDL-C), 1.50 (0.41) mmol/L (58 [16] mg/dL); and
triglycerides, 1.45 (0.73) mmol/L (127 [64] mg/ dL). Lipoprotein levels were
virtually unchanged at the end of both treatment periods (mean difference [95%
confidence interval]): total cholesterol, 0.085 (-0.201 to 0.372) mmol/L (3.3 [
7.8 to 14.4] mg/dL), P=.54; LDL-C, 0.001 (-0.242 to 0.245) mmol/L (0.04 [-9.4 to
9.5] mg/dL), P=.99; HDL-C, 0.050 (-0.028 to 0.128) mmol/L (1.9 [-1.1 to 4.9]
mg/dL), P=.20; triglycerides, 0.047 (-0.229 to 0.135) mmol/L (4.2 [-20.3 to
12.0]) mg/dL, P=.60. Cholesterol absorption (37.5% [10.5%] vs 38.3% [10.7%0],
P=.58), cholesterol synthesis (12.7 [6.5] vs 13.4 [6.6] mg/kg of body weight per
day, P=.64), mevalonic acid excretion (192 [66] vs 187 [66] microg/d, P=.78), and
changes in the ratio of lathosterol to cholesterol in serum (4.4% [24.3%] vs
10.6% [21.1%], P=.62) were not different in garlic and placebo treatment.
CONCLUSIONS: The commercial garlic oil preparation investigated had no influence
on serum lipoproteins, cholesterol absorption, or cholesterol synthesis. Garlic
therapy for treatment of hypercholesterolemia cannot be recommended on the basis
of this study.
PMID- 9634263
TI - Are beta-blockers efficacious as first-line therapy for hypertension in the
elderly? A systematic review.
AB - OBJECTIVE: To assess antihypertensive efficacy of beta-blockers and their effects
on cardiovascular morbidity and mortality and all-cause morbidity compared with
diuretics in elderly patients with hypertension. DATA SOURCE: A MEDLINE search of
English-language articles published between January 1966 and January 1998 using
the terms hypertension (drug therapy) and elderly or aged or geriatric, and
cerebrovascular or cardiovascular diseases, and morbidity or mortality.
References from identified articles were also reviewed. DATA SELECTION:
Randomized trials lasting at least 1 year, which used as first-line agents
diuretics and/or beta-blockers, and reported morbidity and mortality outcomes in
elderly patients with hypertension. DATA SYNTHESIS AND RESULTS: Ten trials
involving a total of 16164 elderly patients (> or =60 years) were included. Two
thirds of the patients assigned to diuretics were well controlled on monotherapy,
whereas less than a third of the patients assigned to beta-blockers were well
controlled on monotherapy. Diuretic therapy was superior to beta-blockade with
regard to all end points and was effective in preventing cerebrovascular events
(odds ratio [OR], 0.61; 95% confidence interval [CI], 0.51-0.72), fatal stroke
(OR, 0.67; 95% CI, 0.49-0.90), coronary heart disease (OR, 0.74; 95% CI, 0.64
0.85), cardiovascular mortality (OR, 0.75; 95% CI, 0.64-0.87), and all-cause
mortality (OR, 0.86; 95% CI, 0.77-0.96). In contrast, beta-blocker therapy only
reduced the odds for cerebrovascular events (OR, 0.75; 95% CI, 0.57-0.98) but was
ineffective in preventing coronary heart disease, cardiovascular mortality, and
all-cause mortality (ORs, 1.01, 0.98, and 1.05, respectively). CONCLUSIONS: In
contrast to diuretics, which remain the standard first-line therapy, beta
blockers, until proven otherwise, should no longer be considered appropriate
first-line therapy of uncomplicated hypertension in the elderly hypertensive
patient.
PMID- 9634264
TI - Sleepiness, driving, and motor vehicle crashes. Council on Scientific Affairs,
American Medical Association.
AB - OBJECTIVE: To assess the contribution of driver sleepiness to highway crashes and
review recent recommendations to change federal hours-of-service regulations for
commercial motor vehicle drivers. DATA SOURCES: Information was derived from a
search of the MEDLINE, Transportation Research Information Service (TRIS), and
Bibliographic Electronic Databases of Sleep (BEDS) databases from 1975 through
1997 and from manual review of the reference lists in relevant journal articles,
government publications, conference proceedings, and textbooks. DATA SYNTHESIS:
Driver sleepiness is a causative factor in 1% to 3% of all US motor vehicle
crashes. Surveys of the prevalence of sleepy behavior in drivers suggest that
sleepiness may be a more common cause of highway crashes than is reflected in
these estimates. About 96% of sleep-related crashes involve passenger vehicle
drivers and 3% involve drivers of large trucks. Risk factors include youth, shift
work, alcohol and other drug use, over-the-counter and prescription medications,
and sleep disorders. CONCLUSIONS: Increased awareness of the relationship between
sleepiness and motor vehicle crashes will promote the health and safety of
drivers and highway users. Physicians can contribute by encouraging good sleep
habits, recognizing and treating sleep-related problems, and counseling patients
about the risks of driving while sleepy. To protect public health and safety, the
American Medical Association recommends continued research on devices and
technologies to detect the signs of sleepiness and prevent the deterioration of
driver alertness and performance. Educational programs about the risks of falling
asleep while driving are needed for physicians, the public, and commercial truck
drivers.
PMID- 9634265
TI - Undertreatment of cancer pain in elderly patients.
PMID- 9634266
TI - The role of the medical profession in physician discipline.
PMID- 9634267
TI - JAMA patient page: auto safety.
PMID- 9634268
TI - [General principles of macroscopic examination of kidney tumors].
AB - We describe the main methods of gross examination of renal tumours. The
pathologic result should refer to the TNM staging, which was achieved by UICC and
AJCC in March, '97.
PMID- 9634269
TI - Gastric cancer.
PMID- 9634270
TI - Evidence-based reviews.
PMID- 9634272
TI - British Society for Haematology annual scientific meeting. Glasgow, United
Kingdom, 27-30 April 1998. Proceedings and abstracts.
PMID- 9634271
TI - Assessing the rigidity and retention of two new types of root canal posts.
PMID- 9634273
TI - The quality measurement matrix: an elegant planning and educational tool.
PMID- 9634274
TI - [Positive-pressure noninvasive artificial ventilation by nasal mask and its role
in pneumology].
PMID- 9634275
TI - [Bronchodilators in COPD--monotherapy or combined? (The annual ERS congress-
Stockholm, Sept. 1996). European Respiratory Society].
PMID- 9634276
TI - [Laparoscopic cholecystectomy in the hands of the left-handed surgeon. A
technical note].
PMID- 9634277
TI - [The statutes of the Romanian Society of Surgery].
PMID- 9634278
TI - Direct enantiomeric separation of mianserin and 6-azamianserin derivatives using
chiral stationary phases.
AB - The direct enantiomeric separation of mianserin and 6-azamianserin and some of
their derivatives, respectively, by means of HPLC using two different chiral
selectors was investigated. For the cellulose-based Chiralcel OD column, a strong
dependence of the lipophilicity of the compounds tested on the retention
behaviour was observed. To some extent, this was also found for the enantiomeric
separation on the amylose-based Chiralpak AD column. In some cases a
complementary behaviour of these two phases was observed: racemic mixtures that
could not be separated by one column could be resolved by the other one.
PMID- 9634279
TI - Capillary electrophoretic and high-performance liquid chromatographic studies of
the enantioselective separation of alpha1-adrenoreceptor antagonists.
AB - Capillary electrophoresis (CE) and chiral stationary phase (CSP) HPLC methods
were investigated for the determination of enantiomeric purity of alpha1
adrenoreceptor antagonists related to WB 4101. In the CE study, the
enantioseparation of the analytes was performed by studying the effect of
different types of cyclodextrin in the buffer, namely heptakis (2,6-di-O-methyl)
beta-cyclodextrin (DMCD), hydroxypropyl-beta-cyclodextrin (HPCD) and beta
cyclodextrin (beta-CD). HPCD was found to be the most effective chiral selector
in the enantioseparation of all the compounds, with high resolution values. A
HPLC method, using immobilised serum protein columns, human serum albumin (HSA)
and alpha1-acid glycoprotein (AGP), was also investigated. Two benzodioxane
racemates were well resolved on a mixed tpe (50% HSA and 50% AGP) column, with
enantioselective binding on AGP column.
PMID- 9634280
TI - [Lamellar bodies in the amniotic fluid--a rapid and accessible test of fetal lung
maturity].
PMID- 9634282
TI - [Reports from the Czech Gynecology and Obstetrical Society Congress held 20-23
March 1997 in Carlsbad].
PMID- 9634281
TI - [Proceedings of the Congress of the Czech Society of Gynecology. Karlovy Vary, 20
23 March 1997].
PMID- 9634283
TI - [Family planning and the law].
PMID- 9634285
TI - [Does hyperoxia affect defensive reflex mechanisms in the respiratory tract?].
PMID- 9634286
TI - [Respiratory tract reflexes after diagnosis and therapy of sleep apnea].
PMID- 9634287
TI - [Noninvasive evaluation of anthracycline cardiotoxicity].
PMID- 9634288
TI - [Signal-averaged electrocardiography as part of comprehensive care of heart
transplant patients].
PMID- 9634289
TI - Adolescent sexual behaviour: results from an Ontario sample. Part 1: Adolescent
sexual activity.
AB - In spite of a variety of broad-based interventions, rates of adolescent sexual
intercourse remain high. Using data from a large longitudinal study, this paper
provides empirical evidence of Canadian adolescent sexual activity rates by age
and gender. The incidence of first sexual intercourse among those 13-15 years was
higher among males than females; by ages 16-17 years, rates were the same for
both genders (25%). Prevalence of sexual intercourse with age; by age 16-17
years, similar rates were reported for both genders (approximately 50%). Analysis
of data over a three-year period indicated that at each age, over 80% of
adolescents reported intermittent or no sexual intercourse. Different factors
predicted the absence of early sexual intercourse for the two genders. These data
provide useful information about Canadian adolescent sexual activity,
particularly related to identifying high risk groups for targeted prevention
interventions.
PMID- 9634291
TI - [Evaluation of the efficiency and safety of the loratadine with pseudoephedrine
combination drug in treatment of seasonal allergic rhinitis].
AB - The aim of the study was to assess efficacy and safety of 5 mg loratadine/120 mg
pseudoephedrine combination drug in patients with seasonal allergic rhinitis. 30
patients allergic to grass pollen were treated with the new drug (Clarinase)
twice a day in 15-day study during grass pollen seasonal. Nasal an non-nasal
symptoms were evaluated for efficacy. Loratadine/pseudoephedrine combination
effected a significant decrease in total symptoms score as well as individual
evaluated symptoms score: nasal stuffiness, itching and discharge, sneezing, eye
itching, tearing and redness of the eyes. The treatments was well tolerated. No
serious side effects were noticed. The incidence of mild sedation, dry mouth,
insomnia and nervousness was only 3 to 7 percent. 5 mg loratadine plus 120 mg
pseudoephedrine was safe and effective in relieving the symptoms of allergic
rhinitis.
PMID- 9634292
TI - [Abstracts of work presented at the 47th Pharmacology Seminar in Kosice (3-5
September 1997)].
PMID- 9634293
TI - Can HSV latency be conquered by current antiviral therapies?
PMID- 9634295
TI - Race and ethnicity in STD analyses.
PMID- 9634296
TI - Sexually transmitted diseases and the Raj.
PMID- 9634294
TI - Influence of ovarian hormones on urogenital infection.
AB - Numerous studies have examined the influence of hormones on infectious diseases
and there is now a wealth of data relating to the more specific effect of the sex
hormones, oestrogen and progesterone, on urogenital infections. The interaction
between these hormones and the immune system is complex and the variation of
hormonal effect between species further complicates the true picture as related
to humans. Although it is difficult therefore to draw general conclusions
regarding predominant effects of specific hormones, there is the suggestion that
oestrogen enhances the pathogenicity of many urogenital micro-organisms. Our
understanding of the influential role played by sex hormones in disease
pathogenesis is at an early stage and illustrates well the importance of drawing
together and interpreting as a whole both epidemiological and molecular studies.
PMID- 9634297
TI - Association of Kaposi's sarcoma associated herpesvirus (KSHV) DNA in
bronchoalveolar lavage fluid of HIV infected individuals with bronchoscopically
diagnosed tracheobronchial Kaposi's sarcoma.
AB - OBJECTIVES: To determine the frequency of detection of Kaposi's sarcoma
associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, DNA
in bronchoalveolar lavage (BAL) fluid from HIV infected individuals with and
without KS and to compare this with the detection rate in peripheral blood. Also
to identify whether KSHV was associated with specific cell types in lavage fluid.
METHODS: Nested PCR was used to detect KSHV DNA in BAL fluid from 41 consecutive
individuals with Kaposi's sarcoma (KS) and in 41 controls with similar CD4
lymphocyte counts. Semiquantification of viral DNA was by end point titration. A
positive cell sorting selection procedure was used to isolate specific BAL fluid
cell types. RESULTS: KSHV DNA was detected in BAL fluid from 24 of 29 (83%)
individuals with a bronchoscopic diagnosis of tracheobronchial KS. None was
detected in 12 individuals with only cutaneous KS, or in 41 matched controls
without KS. In five, KSHV DNA was detected in the cell depleted and cellular
fractions of BAL fluid and in 1/5 in the CD14 (macrophage) fractions. None was
detected in the CD19 (B lymphocyte) or CD4/CD8 (T lymphocyte) fractions.
CONCLUSIONS: There was a clear association between the diagnosis of
tracheobronchial KS and detection of KSHV DNA in BAL fluid. The cell type
supporting KSHV in the respiratory tract is not CD 19 positive and has yet to be
conclusively identified.
PMID- 9634298
TI - Comparison of clinical, histological, and virological symptoms of HPV in HIV-1
infected men and immunocompetent subjects.
AB - OBJECTIVE: We assessed the clinical, histological, and virological features of
anogenital human papillomavirus (HPV) infection, according to their immune status
in HIV-1 infected men, referred for an anogenital examination or treatment, in
comparison with immunocompetent patients. METHODS: The study population comprised
33 HIV-1 infected heterosexual or homosexual men and 38 HIV negative men seen in
a screening and treatment centre for anogenital HPV infections. All patients were
examined with a colposcope. Biopsies were carried out on all subjects with
anogenital lesions for histological studies and HPV detection by Southern blot.
RESULTS: The HIV infected patients had a balanopreputial HPV infection in 70%,
anal in 30%, and urethral in 37%, while HIV negative patients had balanopreputial
lesion in 72%, anal in 26%, and urethral in 16%. Diffuse anogenital lesions were
present in 33% of the HIV infected cases and in 10.5% of HIV negative cases (p <
0.02). Among the HIV infected patients, the genital HPV lesions were
condylomatous in 67.5% of the cases and dysplastic in 57%. HIV negative patients
had condylomatous lesions in 86% of the cases and dysplasic in 14%. The
condylomatous lesions of HIV infected patients had a low grade malignant
histological aspect in 36% of the cases and high grade histological criteria were
found in 22% of the dysplasias. Oncogenic HPVs were detected more frequently in
HIV infected patients (35% v 12%) and more than one HPV type was found in 21.5%
of cases. Neither the anogenital diffusion of the HPV lesions nor their
morphological, histological, and virological features differed significantly in
patient with CD4 cell counts > or < 200 x 10(6)/l. In contrast, patients with CD4
cell counts < 50 x 10(6)/l had a higher risk of several types of HPVs and of
developing a diffuse anogenital infection. CONCLUSION: HIV-1 infected patients
had an increased frequency of high grade anogenital dysplastic lesions and a
higher frequency of HPV infection with multiple and diffuse sites of involvement.
These characteristics of HPV infection were independent of the patients' immune
status up to CD4 cell counts > 50 x 10(6)/l but showed an increased risk when the
CD4 cell count was < 50 x 10(6)/l. The higher frequency of diffuse anogenital
infections among HIV infected men calls for rapid treatment, laser or surgery,
given the association of histological features of intraepithelial neoplasia and
the presence of multiple HPV infection sites which may be the consequence of
immune disturbances, most of which are transmissible potentially oncogenic HPVs.
PMID- 9634300
TI - Moving towards a Cochrane review group in sexually transmitted diseases.
PMID- 9634299
TI - Clinical algorithms for the screening of pregnant women for STDs in Libreville,
Gabon: which alternatives?
AB - OBJECTIVE: Sexually transmitted diseases (STDs) remain one of the major public
health problems in the developing world. To implement a systematic screening of
STDs among pregnant women in Libreville, Gabon, a preliminary cross sectional
study on STD prevalence and risk factors was performed in antenatal clinics. A
score, integrating risk factors and elementary clinical signs for the screening
of STDs, showed higher performances compared with hierarchical algorithms. The
prospective validation of this score based on six criteria (risk factors and
simple clinical signs) was done in 1994-5. The sensitivity (76.7%), compared with
results from other studies, was acceptable for diagnosing cervical infection
(Neisseria gonorrhoeae and/or Chlamydia trachomatis) but the specificity was low
(50.6%). In addition, the diagnostic values for diagnosing vaginal infection
(Trichomonas vaginalis and/or Candida albicans) were poor. We then proposed to
evaluate an alternative flowchart for the screening of cervical and vaginal
infections. METHODS: In this study, 646 pregnant women were enrolled. Each woman
was interviewed and examined by a physician and then was subjected to reference
laboratory examinations. An algorithm in two steps, combining a risk assessment
score at the beginning of a hierarchical process, followed by a second step more
specifically applied to a limited number of women, was developed and evaluated.
RESULTS: The prevalence rate was 11.3% for cervical infection and 39.5% for
vaginal infection. The first step of the algorithm, applied to all pregnant
women, is based on four criteria (age, marital status, dyspareunia, coloured
vaginal discharge). It allows classification of the women into three classes:
high, low, and intermediate risk of cervical infection. Only the patients with
intermediate risk were submitted to further investigations including speculum and
microscopic examination, and subsequently chlamydial antigen detection. This
flowchart was 83.6% and 81.2% sensitive and 63.4% and 62.7% specific for
predicting cervical infection and vaginal infection, respectively. CONCLUSION:
Similar strategies using simple rapid tests for chlamydial and gonococcal
infection would certainly constitute a good diagnostic tool. This theoretical
model needs to be evaluated prospectively, not only to confirm their diagnostic
value but also to evaluate their feasibility, reliability and acceptability, as
well as their cost effectiveness.
PMID- 9634301
TI - More transparency, greater depth.
PMID- 9634302
TI - Racial origin, sexual behaviour, and genital infection among heterosexual men
attending a genitourinary medicine clinic in London (1993-4).
AB - OBJECTIVES: To compare variables of sexual behaviour and incidence of genital
infections among heterosexual men of different racial origins. DESIGN: A
prospective cross sectional study of sexual behaviour reported by a standardised
self administered questionnaire in new patients who presented for screening and
diagnosis. SETTING: A genitourinary medicine clinic in west London. SUBJECTS:
1212 consecutive heterosexual men newly attending in 1993-4. MAIN OUTCOME
MEASURES: Variables relating to sociodemographic status, sexual behaviour, condom
use, sexually transmitted diseases, and other genital infections stratified by
racial origin. RESULTS: There were 941 evaluable heterosexual men of whom the
majority were white (79%) and 17% were black. The black men comprised more
teenagers (11% cf 2%; p < 0.00001), were more likely to be unemployed (26% cf
12%; p < 0.00001), to have commenced intercourse much earlier (45% cf 22% before
aged 16: p < 0.0001), and to have had intercourse with an African woman (14% cf
6%; p < 0.001). Both fellatio (64% cf 96%; p < 0.00001) and cunnilingus (40% cf
92%; p < 0.00001) were practised less frequently by the black men and so too was
anal intercourse (11% cf 27%; p < 0.00001). Similar proportions from both groups
were non-smokers (53% cf 57%), but a significantly higher proportion of the black
men did not drink alcohol (13% cf 5%; p < 0.001). Gonorrhoea (15% cf 1%; p <
0.00001), chlamydial infection (17% cf 8%; p < 0.001), and non-gonococcal
urethritis (37% cf 24%; p = 0.001) were diagnosed more frequently in the black
men. These findings remained significant after logistic regression and are
therefore independently associated with black race. However, there was no
significant difference in numbers of sexual partners in the preceding year
(median 2), nor in condom use with regular and non-regular partners. The Asian
men had commenced intercourse later (mean 19.1 years) than both the black men
(mean 15.9 years) and the white men (mean 17.3 years). CONCLUSIONS: Compared with
white men, black men attending a genitourinary medicine clinic were much more
likely to be unemployed, to have commenced intercourse earlier and to have
urethral infection. They were much less likely to practice fellatio, cunnilingus,
or anal intercourse. However, there was no difference between the two racial
groups in respect of numbers of sexual partners and condom use.
PMID- 9634303
TI - Racial origin, sexual lifestyle, and genital infection among women attending a
genitourinary medicine clinic in London (1992).
AB - OBJECTIVES: To compare variables of sexual behaviour and incidence of genital
infections among women of different racial origins and lifestyles. DESIGN: A
prospective cross sectional study of sexual behaviour reported by a standardised
self administered questionnaire in new patients who presented for screening and
diagnosis. SETTING: A genitourinary medicine clinic in west London. SUBJECTS:
1084 consecutive women newly attending in 1992. MAIN OUTCOME MEASURES: Variables
relating to sociodemographic status, sexual lifestyle, condom use, sexually
transmitted diseases, and other genital infections stratified by racial origin.
RESULTS: There were 948 evaluable women, of whom 932 (98.3%) were heterosexual
and 16 (1.7%) were lesbian. Previous heterosexual intercourse was reported by 69%
of lesbian women and their most frequent diagnosis was bacterial vaginosis (38%).
The majority of heterosexual women were white (78%) and 16% were black. The black
women were more likely to be teenagers (18% cf 8%; p = 0.0004) or students (28%
cf 15%; p = 0.0008), and to have had an earlier coitarche (48% cf 38% before aged
17; p < 0.004). They also had a higher proportion of pregnancies (58% cf 38%; p <
0.00001) and births (38% cf 20%; p < 0.00001). The white women showed
significantly more sexual partners during the preceding year (p = 0.004) and in
total (p < 0.00001) and more reported non-regular partners (48% cf 35%; p =
0.004) with whom they were more likely to use condoms (p = 0.009). However, the
black women were more likely to have gonorrhoea (7% cf 2% p < 0.0003), chlamydial
infection (12% cf 5% p < 0.002), trichomoniasis (10% cf 2% p < 0.00001), or to
sexual contacts of men with non-gonococcal urethritis (19% cf 12% p < 0.02). They
were less likely to have genital warts (3% cf 12% p = 0.002). Logistic regression
showed that all these variables were independently associated with the black
women. The Asian women (2%), none of whom had a sexually transmitted disease, had
commenced intercourse later (mean 19.7 years) than both black women (mean 16.8
years) and white women (mean 17.6 years). CONCLUSIONS: Sexual intercourse
commenced approximately 1 year earlier in the black women, who were more likely
to have become pregnant, had children, and to have acquired a bacterial sexually
transmitted infection than were the white women.
PMID- 9634304
TI - HIV infection among family planning clinic attenders in Glasgow: why prevalence
has remained low in this general population group.
AB - OBJECTIVE: During 1991-2, unlinked anonymous testing of dried blood spots from
neonatal metabolic screening cards showed the prevalence of HIV among
childbearing women from Glasgow to be extremely low at 0.01%. A study was
conducted to determine if non-pregnant sexually active women who engaged in
unprotected sexual intercourse were more likely to be infected than those who
were pregnant. METHODS: Unlinked anonymous HIV testing of urine specimens
submitted by attenders of the family planning clinic in Glasgow for pregnancy
testing. RESULTS: Of 11,990 urine specimens tested, 7664 were from women with a
negative pregnancy test and two of these were HIV positive (0.026%); none of the
remainder from those with a positive pregnancy test had HIV antibodies.
CONCLUSION: No hidden epidemic was unearthed among a population which had engaged
in unprotected sexual intercourse and was not pregnant. Other data from Glasgow
strongly suggest that the control of HIV transmission among the city's population
of current injectors (HIV prevalence, 1% of 8500) has prevented the spread of
infection into its wider heterosexual population. It is essential that preventive
measures which have been responsible for this public health success should be
maintained.
PMID- 9634305
TI - Evaluation of a targeted HIV prevention programme among female commercial sex
workers in the south of Thailand.
AB - OBJECTIVE: To evaluate a targeted HIV prevention programme among female
commercial sex workers (CSWs) in the south of Thailand. SUBJECTS AND METHODS: A
pretest-post-test comparison group study was carried out in Sungai Kolok and
Betong between June and December 1994. In June 408 CSWs were entered in Sungai
Kolok (the intervention area) and 343 CSWs were enrolled in Betong (the
comparison area). In December 1994, 416 women were enrolled in Sungai Kolok and
342 in Betong. Of these women 37% (n = 283) also participated in the June survey.
All women completed an oral interview and blood samples were collected for HIV
serology. The intervention programme consisted of an informational and
educational campaign and peer educator training. RESULTS: Increase in knowledge
and perceived vulnerability was more pronounced in the intervention area but did
not translate into a greater increase in condom use. Refusal of customers
unwilling to use a condom and manager support in doing so were the only factors
independently related to positive changes in condom use. HIV prevalence
(approximately 20%) and incidence (approximately 4.2 per 100 women years) were
the same in both study locations. Women in the intervention area reported
significantly fewer customers and income from sex work, possibly as a result of a
coincidental police campaign to suppress (child) prostitution. CONCLUSIONS: HIV
incidence among CSWs in the south of Thailand is still high. Prevention
programmes should focus on improvement of negotiation and refusal skills and
manager support in using condoms.
PMID- 9634306
TI - Analysis of quinolone resistance mechanisms in Neisseria gonorrhoeae isolates in
vitro.
AB - BACKGROUND AND OBJECTIVES: Gonococcal fluoroquinolone resistance is now a
significant problem in Japan. We generated gonococcal mutants resistant to
norfloxacin in vitro from norfloxacin sensitive isolates and analysed the
contribution of three known mechanisms of quinolone resistance in Neisseria
gonorrhoeae. MATERIALS AND METHODS: Three clinical isolates of N gonorrhoeae
susceptible to norfloxacin were exposed to increasing concentrations of
norfloxacin. To identify mutations in the gyrA and parC genes of the gonococcal
mutants, the quinolone resistance determining regions of the gyrA and parC genes
were polymerase chain reaction (PCR) amplified and the PCR products were directly
sequenced. Norfloxacin accumulation in the gonococcal cells was also measured.
RESULTS: The MICs of norfloxacin for three variants containing a single GyrA
mutation were 16-fold higher than that for their parent isolates. A variant
showing reduced norfloxacin accumulation in the cells, without mutations in the
GyrA or ParC proteins, was also less sensitive to norfloxacin, with a 16-fold
increase in the MIC, compared with the parent strain. The MIC of norfloxacin for
a variant which contained a single GyrA mutation with reduced norfloxacin
accumulation in the cells was 128-fold higher than for the parent strain. A
variant containing mutations in both GyrA and ParC proteins with reduced
accumulation of norfloxacin in the cells showed a 256-fold increase in the
norfloxacin MIC compared with the parent strain. There was no variant containing
a ParC mutation without the simultaneous presence of a GyrA mutation.
CONCLUSIONS: The results from this study suggest that not only a mutation in the
gyrA gene but also reduced drug accumulation in cells contributes to the
development of fluoroquinolone a mutation in the gyrA gene contributes to a high
level of fluoroquinolone resistance in gonococci with decreases in accumulation
in cells having an additional but lesser effect.
PMID- 9634307
TI - Oral sex and the transmission of viral STIs.
AB - OBJECTIVE: To review the literature on the role of oral sex in the transmission
of viral sexually transmitted infections (STIs). METHOD: A Medline search was
performed using the keywords oro-genital sex, and those specific to each
infection. Further references from each article identified by Medline were also
included, as were relevant references from "Current contents". CONCLUSIONS: Oral
sex is a common sexual practice among both heterosexual and homosexual couples.
The evidence suggests that HIV transmission can take place through oro-genital
sex from penis to mouth and vagina to mouth. Case reports describe apparent
transmission from mouth to penis although this appears less likely. The risk of
oro-genital transmission of HIV is substantially less than from vaginal and anal
intercourse. Receptive oro-genital sex carries a small risk of human
papillomavirus infection and possibly hepatitis C, while insertive oro-genital
contact is an important risk factor for acquisition of HSV 1. Oro-anal
transmission can occur with hepatitis A and B. The transmission of other viruses
may occur but is unproved. The relative importance of oral sex as a route for the
transmission of viruses is likely to increase as other, higher risk sexual
practices are avoided for fear of acquiring HIV infection.
PMID- 9634308
TI - Polymerase chain reaction detection of Haemophilus ducreyi DNA.
AB - OBJECTIVES: To develop a polymerase chain reaction (PCR) method to detect
Haemophilus ducreyi DNA in cultured isolates and clinical material. METHODS:
Primers specific to the H ducreyi 16s rRNA gene were synthesised. PCR conditions
were optimised and products were verified by restriction endonuclease digestion
and agarose gel electrophoresis. RESULTS: The method was able to detect all 28 H
ducreyi strains tested; specificity was demonstrated using lysates of 12 related
organisms. Applied to clinical samples from genital ulcer swabs obtained in
Harare, Zimbabwe, H ducreyi DNA was detected in repeated assays in 35 clinical
samples. CONCLUSION: PCR amplification using primers from the 16s rRNA gene may
be a useful alternative to culture for the detection of H ducreyi and the
diagnosis of chancroid.
PMID- 9634310
TI - Sixth European Conference on Clinical Aspects and Treatment of HIV Infection,
Hamburg, Germany, 11-15 October 1997.
PMID- 9634309
TI - Pooling of urine specimens for PCR testing: a cost saving strategy for Chlamydia
trachomatis control programmes.
AB - OBJECTIVES: To evaluate pooling of first catch urine (FCU) specimens as a cost
effective strategy for chlamydia testing. METHODS: Mock specimens were pooled
with and without dilution to determine optimal pool size and ease of work flow.
The performance of the Amplicor Chlamydia trachomatis PCR assay on pooled
specimens was compared with individual testing using 370 FCU specimens from
asymptomatic men presenting to an STD clinic. Cost savings associated with
pooling were estimated. RESULTS: Using mock specimens, the sensitivity and
specificity of the Amplicor PCR assay were not affected by pool sizes of two and
five, but at a pool size of 10 decreased sensitivity due to inhibition was
observed in one of five mock pools when the pooling method which involved no
dilution was used. Archived FCU specimens from a study of 370 asymptomatic men
were combined consecutively into 74 pools of five and tested by PCR. Of the 18
pools that contained positive specimens, 17 were PCR positive. Compared with
testing FCU specimens individually, pooling resulted in a sensitivity of 95%,
specificity of 100%, and a cost savings of 57% based on reduced number of tests
required. CONCLUSION: Depending on the prevalence of infection, pooling of FCU
specimens for PCR testing may result in cost savings compared with testing
specimens individually. Further evaluations to validate this strategy using fresh
FCU specimens are needed.
PMID- 9634311
TI - International Congress of Sexually Transmitted Diseases, 19-22 October 1997.
PMID- 9634312
TI - Age and sexual risk behaviour.
PMID- 9634313
TI - Severe hyponatraemia and severe hyperkalaemia in an HIV positive patient who
received high dose co-trimoxazole.
PMID- 9634314
TI - Visualisation and quantification of HIV related brain atrophy using registered
serial magnetic resonance imaging.
PMID- 9634315
TI - Do junior doctors know what to do if they have a needlestick injury?
PMID- 9634316
TI - Second generation heterosexual transmission of HIV-1 infection from women
infected in the United Kingdom.
PMID- 9634317
TI - Acceptability of clinics for sexually transmitted diseases among users of the
"gay scene" in the West Midlands.
PMID- 9634318
TI - Microbiological diagnosis of gonorrhoea.
PMID- 9634319
TI - Sample size and diagnostic test evaluations.
PMID- 9634320
TI - Azithromycin for the treatment of donovanosis.
PMID- 9634322
TI - Hepatitis B virus infection in patients attending a genitourinary medicine
clinic: risk factors and vaccine coverage.
AB - BACKGROUND: The hepatitis B virus (HBV) immunisation policy in the United Kingdom
includes offering vaccines selectively to those at risk by sexual contact. Among
genitourinary medicine (GUM) clinic attenders, homosexual men are offered
vaccine, but estimates of the vaccine uptake are required to monitor policy and
estimate the possible impact on transmission; heterosexuals are not routinely
offered vaccine, but this policy might change if the prevalence was found to be
high. OBJECTIVE: To determine the prevalence of HBV infection and vaccine uptake
among patients attending a GUM clinic. METHODS: HBV seroprevalence determined by
unlinked anonymous testing of consecutive blood samples sent for syphilis
serology. Demographic and risk factor data and history of HBV immunization
extracted from clinic notes before unlinking. Prevalence data were compared with
a population of first time blood donors from the same area. SETTING: Open access
GUM clinic in central London. RESULTS: Samples were obtained and tested from 441
homosexual and 527 heterosexual men and from 821 women over a 4 month period in
1990. After exclusion of injecting drug users and their sexual partners (n = 30)
and HBV carriers attending for follow up (n = 12), the prevalence of antibody to
HBV core (anti-HBc) was 38.7% in homosexual men, 5.9% in heterosexual men, and
3.5% in women (50.0%, 6.0%, 3.7% respectively if previous vaccinees were also
excluded). The prevalence of HBV surface antigen positivity was 4.2%, 0.60%, and
0.39% respectively after exclusion of vaccinees (chi(2) p < 0.001 for homosexual
men versus others). The prevalence of the anti-HBc in first time blood donors was
1.1% (8/749). Among male GUM clinic attenders, the prevalence of anti-HBc was
higher in those of non-UK origin or place of birth and/or non-white ethnicity
(odds ratios 2.87, 95% CI 1.57-5.24 and 8.06, CI 3.39-19.1, in homosexuals and
heterosexuals respectively). In homosexual men anti-HBc prevalence increased with
age (OR 1.05, CI 1.02-1.07 for each year) and lifetime number of STDs (OR 6.36,
CI 3.77-10.8 for > or = 2 versus < 2) and in clinic reattenders compared with new
patients (OR 5.42, 95% CI 3.32-9.16). Among heterosexuals, age was associated
with anti-HBc prevalence in women (OR 1.09, CI 1.04-1.12) but not men (OR 0.99,
95% CI 0.95-1.02). There were no other associations in heterosexuals. A history
of HBV immunisation in homosexual men was recorded in 13/131 (9.9%) of new
patients and 103/305 (33.8%; OR 4.63, CI 2.49-8.60) clinic reattenders.
CONCLUSIONS: Although higher than a sample of blood donors, the prevalence of
serological markers of HBV infection among heterosexuals was low, providing
little support for extending HBV immunisation to all heterosexuals attending GUM
clinics as a targeted strategy for control of HBV infection. Homosexual men
remain at high risk of infection, but many are now being immunised. Efforts to
improve compliance with existing vaccine policies in GUM clinics should be
encouraged.
PMID- 9634323
TI - A randomized controlled trial comparing nonoxynol-9 lubricated condoms with
silicone lubricated condoms for prophylaxis.
AB - OBJECTIVE: We tested the effect of nonoxynol-9 (N-9) in condom lubrication on the
risk of acquiring STD and genital discomfort. METHODS: The study was a triple
masked, randomised controlled trial comparing N-9 lubricated condoms with plain
silicone lubricated condoms among Dominican female sex workers. RESULTS:
Randomisation provided two groups (313 for N-9 and 322 for plain) similar in
baseline characteristics, but extensive loss to follow up occurred (56 women in
each group completed the 24 week follow up). Most vaginal acts with clients were
protected with condoms (99% of vaginal sex) but fewer acts with non-clients were
protected (43% of vaginal sex). No significant differences occurred in rates of
cervical infections (N-9 = 3.4 per 100 person months v plain = 2.8),
trichomoniasis (N-9 = 2.8 v plain = 3.6), or discomfort rates (N-9 = 0.82 v plain
= 0.92). CONCLUSIONS: Plain silicone lubricated condoms are as effective as N-9
lubricated condoms, cost less, have longer expected shelf life, and therefore may
be the better condom to provide.
PMID- 9634324
TI - Community based study of sexually transmitted diseases in rural women in the
highlands of Papua New Guinea: prevalence and risk factors.
AB - OBJECTIVE: To estimate the prevalence of sexually transmitted diseases (STDs) and
determine their risk factors/markers among a rural population of women in the
highlands of Papua New Guinea. METHODS: Community based random cluster sample of
women of reproductive age were interviewed and examined and had specimens
collected for laboratory confirmation of chlamydial and trichomonal infection,
gonorrhoea, syphilis, and bacterial vaginosis. RESULTS: Chlamydia trachomatis was
detected in 26%, Trichomonas vaginalis in 46%, Neisseria gonorrhoeae in 1%,
syphilis in 4%, pelvic inflammatory disease (PID) (diagnosed clinically) in 14%,
and bacterial vaginosis in 9% of 201 women. 59% of the women had at least one
STD. In a multivariate logistic regression analysis taking the clustered sampling
into account, independent risk factors for chlamydial infection were age < or =
25 years, < four living children, visualization of yellow mucopurulent
endocervical secretions on a white swab, and bacterial vaginosis. Being married
to a man who did not have other wives was protective. For trichomonal infection,
independent risk factors were having no formal education, infertility, more than
one sexual partner in the previous 12 months, treatment for genital complaints in
the previous 3 months, abnormal vaginal discharge detected on examination, and
chlamydial infection. Similar levels of trichomonal infection were found in all
age groups. Among married women, rates of infection correlated with their
perception of their husband having had other sexual partners in the previous 3
months, and this relationship was significant for chlamydial infection among
women over 25. CONCLUSION: STDs are a major problem in this population, with the
risk factors varying by outcome. Current treatment regimens are inappropriate
given the high prevalence of trichomonal infection, and the available services
are inadequate. Effective interventions are required urgently to reduce this
burden and to prevent the rapid transmission of HIV.
PMID- 9634321
TI - Molecular events in uterine cervical cancer.
AB - OBJECTIVE: To review the literature regarding the molecular events which occur in
the development of uterine cervical cancer, with particular reference to human
papillomavirus (HPV) infection. METHODOLOGY: Bibliographic searches of Medline
and the ISI citation databases using appropriate keywords, including the
following: papillomavirus, cervix, pathology, cyclin, chromosome, heterozygosity,
telomerase, smoking, hormones, HLA, immune response, HIV, HSV, EBV. CONCLUSIONS:
It has become clear that most cervical neoplasia, whether intraepithelial or
invasive, is attributable in part to HPV infection. However, HPV infection alone
is not sufficient, and, in a small proportion of cases, may not be necessary for
malignant transformation. There is increasing evidence that HPV gene products
interfere with cell cycle control leading to secondary accumulation of small and
large scale genetic abnormalities. This may explain the association of viral
persistence with lesion progression but, in many patients, secondary factors,
such as smoking and immune response, are clearly important. However, the
mechanisms involved in the interaction between HPV and host factors are poorly
understood.
PMID- 9634325
TI - HIV infection and high risk behavior among patients attending an STD referral
clinic in Prague, Czech Republic.
AB - OBJECTIVE: This survey was conducted to determine the prevalence of HIV infection
and associated risk behaviour in a high risk population of clients attending an
STD clinic in Prague, Czech Republic. METHODS: Between September 1994 and January
1995, clients entering the Apolinar STD clinic in Prague, Czech Republic, were
enrolled in a blinded, unlinked HIV antibody seroprevalence study. Non
identifying demographic characteristics, STD diagnoses, HIV risk exposures, and
voluntary HIV testing experience were extracted from medical charts. RESULTS: Of
1394 patients for whom serum was available for testing, one was positive for HIV
(HIV prevalence 0.07%, 95% confidence interval (CI) 0.01, 0.41%). This person was
one of 28 men having sex with men (MSWM) (HIV prevalence among MSWM 3.6%, 95% CI
0.6, 17.7%). Among the 775 male clients, 75.5% had heterosexual unprotected sex,
11.1% had sex with high risk partners or prostitutes, 3.6% were MSWM, 1.0% were
injecting drug users (IDUs), 0.7% were both MSWM and IDUs, and 6.8% and 1.8% had
other or no recognized risk for HIV/STDs, respectively. Among the 619 female
clients, 74.5% had heterosexual unprotected sex, 11.6% were prostitutes, 7.8% had
sex with high risk partners, 1.1% were IDUs, and 3.9% and 2.3% had other or no
recognised risk, respectively. The 304 adolescent patients (age 11-19 years)
differed significantly (p < 0.05) in risk behaviour and STD diagnoses from the
1090 patients who were 20 years and older. Adolescents were significantly more
likely to be female (58.6% v 40.5%, OR = 2.1), IDUs (3.6% v 0.4%, OR = 10.2),
prostitutes (8.9% v 4.7%, OR = 2.0), and have sex partners with STDs (7.6% v
4.4%, OR = 1.8). The adolescent patients were also significantly more likely to
be diagnosed with gonorrhoea (21.1% v 12.3%, OR = 1.9) and non-gonococcal
urethritis (27.6% v 17.2%, OR = 1.8), and significantly less likely to have been
tested previously for HIV (19.1% v 31.9%, OR = 0.5). CONCLUSIONS: HIV infection
is currently uncommon in this population. However, the high rates of unprotected
sex, prostitution, injecting drug use, and STDs, especially among adolescents,
provide the basis for an epidemic in this population. Aggressive prevention
education should be started before adolescence.
PMID- 9634326
TI - Characteristics associated with prevalent HIV infection among a cohort of sex
workers in Cameroon.
AB - OBJECTIVE: To determine prevalence of HIV infection in a cohort of female sex
workers in Cameroon, and to describe characteristics associated with HIV
infection in this population. METHODS: In a cross sectional study, 2260 female
sex workers in Cameroon were interviewed and screened for HIV serostatus. A
standardised questionnaire was used to collect information on sociodemographic
characteristics and sexual and health behaviours. RESULTS: Seropositive
participants (18%) were more likely to be over age 25, have four or more
children, live in Yaounde or Douala for 5 years or less, solicit clients in their
homes or on the street, have a low educational level, earn a weekly income of
less than $24, and have no other occupation outside of sex work. A logistic
regression model of selected sociodemographic characteristics indicated that
women at particularly high odds of HIV infection were older, poorer, and new
immigrants to their city of residence. CONCLUSION: This seroprevalence study
found a lower HIV prevalence than had been previously reported. Although our
results are different, this group is still at much higher risk of HIV infection
than the population as a whole.
PMID- 9634327
TI - The tampon test for trichomoniasis: a comparison between conventional methods and
a polymerase chain reaction for Trichomonas vaginalis in women.
AB - OBJECTIVES: Trichomonas vaginalis is the most common STD worldwide and the
infection has been linked with an increased risk of HIV transmission. We present
a detailed comparison between conventional collection and testing methods and the
polymerase chain reaction (PCR) tampon test for T vaginalis. METHODS: Women were
tested for the presence of T vaginalis by PCR analysis of a tampon specimen and
by conventional methods which included one or more of the following: culture and
microscopy from a high vaginal swab (HVS) or endocervical swab (ECS), and
microscopy of a Papanicolaou (Pap) smear. RESULTS: T vaginalis was detected in
51/590 (8.6%) conventional tests and 93/590 (15.8%) tampon specimens. Retesting
of all tampon PCR positive specimens confirmed 89/93 (95.7%) tests. Using the
tampon PCR as the reference, the sensitivities of the different conventional
sampling and testing methods for the detection of T vaginalis were 8.3% (5/60)
for ECS microscopy or culture, 31% (13/42) for HVS microscopy or culture, 52.8%
(19/36) for HVS directly inoculated into Trichomonas medium and 59.4% (38/64) for
Pap smear. CONCLUSIONS: No conventional test in the remote setting has comparable
sensitivity to PCR. The Pap smear is the next most sensitive, but requires a
speculum examination. The use of PCR will allow inclusion of T vaginalis into STD
screening programmes in both developed (lower prevalence) and developing (higher
prevalence) countries.
PMID- 9634328
TI - Sensitivity of the ligase chain reaction assay for detecting Chlamydia
trachomatis in vaginal swabs from women who are infected at other sites.
AB - OBJECTIVE: To assess the sensitivity of the ligase chain reaction (LCR) assay for
Chlamydia trachomatis in vaginal swabs from women who were positive in cervical
samples and/or urines. SUBJECTS: 413 women attending the genitourinary medicine
clinic, St. Mary's Hospital, Paddington. METHODS: The LCR assay was used to test
vaginal swabs from 46 women who were C trachomatis positive at one or both of the
other sites by direct fluorescent antibody (DFA) staining, by an enzyme
immunoassay (EIA), or by the LCR assay. RESULTS: The LCR assay of vaginal swabs
had the following sensitivity values using confirmed positive results: 93%
(41/44) compared with DFA staining of cervical deposits, 93% (41/44) compared
with the LCR assay of cervical samples, 93% (28/30) compared with an EIA for
cervical samples, 91% (39/43) compared with DFA staining of urine deposits, and
93% (39/42) compared with the LCR assay of urine. Four women had vaginal swab
samples negative by the LCR assay; one was positive only in the urine and two had
cervical samples containing a small number of chlamydial elementary bodies.
CONCLUSION: Testing vaginal swabs by the LCR assay is a sensitive method of
detecting chlamydial infection; the results suggest that this procedure could be
used as an alternative to examining urines in a screening programme for
chlamydial infection in the community.
PMID- 9634329
TI - Extragenital donovanosis in a patient with AIDS.
AB - A case of extragenital donovanosis in a patient with AIDS is reported from
Zimbabwe. Despite the rarity of donovanosis in Zimbabwe it is important that
health workers are familiar with this disease since donovanosis increases the
risk of HIV transmission and appropriate treatment is often successful even in
patients with severe immunodeficiency.
PMID- 9634330
TI - Should preventive antiretroviral treatment be offered following sexual exposure
to HIV? The case for.
PMID- 9634331
TI - Should preventive antiretroviral treatment be offered following sexual exposure
to HIV? Not yet!
PMID- 9634332
TI - Can we predict the prognosis of HIV infection? How to use the findings of a
prospective study.
PMID- 9634333
TI - A short history of the Medical Society for the Study of Venereal Diseases on its
75th birthday. The Ninth Harrison Lecture.
PMID- 9634334
TI - Relatively high risk of sexually transmitted and other genital diseases among
women from Surinam and The Netherland's Antilles living in Amsterdam.
PMID- 9634336
TI - Peer education and community based HIV prevention for homosexual men: peer led,
evidence based, or fashion driven?
PMID- 9634335
TI - Once weekly ganciclovir as prophylaxis is unacceptable to patients.
PMID- 9634337
TI - Update of the CDC STD treatment guidelines: changes and policy.
PMID- 9634338
TI - Guidelines for the management of herpes simplex virus infection in pregnancy.
PMID- 9634340
TI - The evolution of veterinary surgical oncology.
AB - Tremendous change and progress have occurred in the field of oncology over the
last several decades. Progression in diagnostic techniques, patient support,
adjuvant therapies and surgeon training has allowed the field of surgical
oncology to make continued improvements in the human cancer field. Although a
relatively young field, veterinary surgical oncology has followed in the
progressive footsteps of our human counterparts. This article describes the
evolution of this rapidly expanding field of veterinary medicine.
PMID- 9634339
TI - Oral sex and transmission of non-viral STIs.
AB - OBJECTIVES: To review the literature on the role of oral sex in the transmission
of non-viral sexually transmitted infections (STIs). METHOD: A Medline search was
performed using the keywords oro-genital sex, and those specific to each
infection. Further references were then taken from each article read.
CONCLUSIONS: Oral sex is a common sexual practice between both heterosexual and
homosexual couples. Oro-genital sex is implicated as a route of transmission for
gonorrhoea, syphilis, Chlamydia trachomatis, chancroid, and Neisseria
meningitidis. Other respiratory organisms such as streptococci, Haemophilus
influenzae, and Mycoplasma pneumoniae could also be transmitted by this route.
Fellatio confers risk for acquisition of infection by the oral partner.
Cunnilingus appears to predispose to recurrent vaginal candidiasis although the
mechanism for this is unclear, while a link between oro-genital sex and bacterial
vaginosis is currently being studied. Oro-anal sex is implicated in the
transmission of various enteric infections. In view of the increased practice of
oral sex this has become a more important potential route of transmission for
oral, respiratory, and genital pathogens.
PMID- 9634341
TI - Principles of tumor biopsy.
AB - Tumor biopsy is the cornerstone of sound therapeutic decision making in oncology.
Although there are multiple ways to obtain a biopsy from any given tumor, each
individual procedure requires careful planning to ensure that the optimal
treatment course is not compromised. Knowledge of the principles and techniques
underlying biopsy is imperative to ensure an accurate diagnosis with minimal
morbidity. This article describes the principles of biopsy and commonly used
sampling techniques and where these procedures are most applicable. Appropriate
tissue handling, interpretation of results, and some special techniques are also
described.
PMID- 9634342
TI - Preoperative patient planning and margin evaluation.
AB - Preoperative assessment of the cancer patient can be broken down into: (1) What
is it? (2) Where is it? and (3) What is the status of the patient? Evaluation of
local disease begins with obtaining and interpreting cytologic or histologic
(biopsy) samples. Tumor staging involves the assessment of tumor invasion into
local tissues, draining lymph nodes, and distant sites, especially the pulmonary
parenchyma. Staging is performed with the aid of imaging techniques and special
procedures such as lymph node and bone marrow aspiration. Because many veterinary
cancer patients are geriatric, examination of physiologic patient status through
laboratory and other diagnostic avenues is vital to the appropriate selection and
success of therapy. After these questions are answered, appropriate treatment
options and an ultimate treatment plan can be formulated. This article describes
logical and practical approaches for diagnosis, staging, patient assessment, and
treatment planning of the animal presented with tumor disease. With appropriate
preoperative assessment, we can offer our patients and clients the best care
possible.
PMID- 9634343
TI - Chemotherapy and the surgery patient: principles and recent advances.
AB - Surgery is the mainstay of cancer therapy, yet there is mounting information
demonstrating that chemotherapy is effective for the treatment of a wide variety
of malignancies in dogs, cats and horses. Chemotherapy is not only being used to
delay or eliminate metastatic disease, but also to enhance the local control of
malignancies. New drugs and innovative combinations of chemotherapeutic agents
are being evaluated at an ever increasing rate. Anticancer drugs are being
delivered safer and more effectively because patients are being treated in new
ways such as intralesionally or within body cavities. These agents are also being
scheduled in more effective ways such as prior to, during, or after surgery.
Techniques are being developed for drugs to be inhaled to reduce metastatic
pulmonary disease. The purpose of this article is to review the general
principals of cancer chemotherapy, the various toxicoses associated with these
drugs, as well as examples of how chemotherapy has been used in combination with
surgery.
PMID- 9634344
TI - Principles of adjunctive radiation therapy.
AB - Radiation therapy is becoming increasingly available to the practicing
veterinarian. It is important that veterinarians be familiar with mechanisms and
biologic effects of radiation used as a therapeutic modality in the treatment of
cancer. It is also important that the veterinarian understand oncologic decision
making and indications for various modalities including radiation therapy,
surgery, and chemotherapy. Surgery and radiation therapy can be particularly
complementary in combined therapy to achieve a functional and cosmetic result.
This review introduces basic radiation therapy concepts, particularly regarding
combination of radiation and surgery in the treatment of cancer in animals.
PMID- 9634345
TI - Principles of oncologic orofacial surgery.
AB - The most common orofacial tumors of dogs are malignant melanoma, squamous cell
carcinoma, fibrosarcoma, osteosarcoma, and acanthomatous epulis. These tumors
vary significantly in their metastatic potential, but are consistently locally
invasive. Bone involvement is common, and complete excision often requires
partial mandibulectomy or partial maxillectomy. Survival times after surgery are
most strongly influenced by tumor type (or metastatic rate) and tumor location.
Recent large retrospective studies have reported median survival times ranging
from 4.6 to 26 months. The most common oral tumor of cats is squamous cell
carcinoma. This is a highly invasive tumor that occasionally can be effectively
treated with surgery alone, but that often requires a combination of surgery and
radiation therapy.
PMID- 9634346
TI - Tumor biology and pathology.
AB - The correct pathologic diagnosis of tumor type affecting the veterinary patient
is of utmost importance to the veterinary surgical oncologist. The surgical
oncologist may be presented with benign or malignant diseases, and an accurate
pathologic diagnosis may be necessary to distinguish between the two conditions.
In either case, assessment of surgical margins to determine completeness of
surgical removal is necessary. In cases of malignancy, the pathologist should
grade the tumor, if appropriate, and be able to perform specialized techniques,
such as immunohistochemistry, if a diagnosis is in question. The surgical
oncologist needs to understand the principles of tissue collection, fixation, and
submission to help the pathologist provide an accurate diagnosis. Finally, the
oncologic surgeon and surgical pathologist need to establish a cooperative
working relationship and function as a team to discuss difficult cases. This will
ensure the best treatment for the veterinary patient.
PMID- 9634347
TI - Principles of oncologic abdominal surgery.
AB - The principles of abdominal oncologic surgery parallel the general principles of
all types of oncologic surgery with some variations peculiar to the abdomen. Due
to the presence of multiple organ systems within the abdominal cavity, many types
of cancer can develop. The surgeon must be prepared to perform several different
abdominal procedures depending on the organ system involved and the extent of the
cancer. The surgeon as oncologist must be aware of the tumor type, its expected
behavior, and current treatment options. This article describes the principles of
performing cancer surgery, including preparation for abdominal exploration,
methods to facilitate tumor removal, and ways of avoiding tumor recurrence.
PMID- 9634348
TI - Thoracic surgical oncology.
AB - Thoracic surgical oncology involves surgical treatment of lesions of the thoracic
wall, pulmonary parenchyma, or mediastinum (also including heart, esophagus, or
trachea). The most common neoplasms of the thoracic wall are osteosarcoma and
chondrosarcoma. Histopathologic type, the use of chemotherapy for osteosarcoma,
and completeness of surgical margins are prognostic for survival. Relative to
solitary pulmonary masses, carcinomas are most common, with histopathologic type,
tumor size, tumor grade, and lymph node status prognostic for survival. Of the
aforementioned variables, lymph node status is the most significant. Extensive
preoperative workup, including bronchoscopy and transthoracic fine needle
aspiration of solitary lung masses, is usually not recommended. Thymomas are the
most common surgical mediastinal mass. Patients are frequently affected with
paraneoplastic syndromes including myasthenia gravis, polymyositis, and nonthymic
neoplasia. Patients without megaesophagus with surgically resectable masses have
an excellent prognosis for survival. Provision of analgesia after surgery in
thoracotomy patients is extremely important. Carefully selected analgesic agents
in thoracotomy patients are far less damaging to cardiovascular status than is
tachycardia from excessive pain. Given these and other guidelines, perioperative
mortality in thoracotomy patients is minimal, and long-term survival in selected
patients is excellent.
PMID- 9634349
TI - Surgery for skeletal sarcomas.
AB - Skeletal neoplasms in pet animals are uncommon, but can represent a diagnostic
and treatment challenge for the veterinary clinician. Osteosarcoma represents the
most common histology of primary bone tumor and although the prognosis after
treatment is still gaurded, major strides have been made in the treatment of this
disease. Treatment success, however, requires a multidisciplinary approach.
Additional histologic types cannot be ignored from the diagnosis of cases
presenting as bone neoplasms, and many of these can have excellent long-term
prognoses if treated appropriately. This article discusses the presentation,
diagnosis, and treatment of skeletal neoplasms in general with a specific
emphasis on osteosarcoma.
PMID- 9634350
TI - Principles of treatment for soft tissue sarcoma.
AB - Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue
elements and are grouped together based on a common biologic behavior. The most
common histologic types include malignant peripheral nerve sheath tumors
(schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and
malignant fibrous histiocytoma. These tumors are relatively slow growing yet
locally invasive with a high rate of recurrence following conservative
management. Appropriate preoperative planning and aggressive surgical resection
often result in long-term remission or cure. Identification and evaluation of
resection margins are paramount in appropriate case management. The addition of
radiotherapy after surgical resection can aid in remission for incompletely
resected masses. Systemic chemotherapy for STS should be considered for high
grade tumors with a moderate metastatic potential. Potential prognostic factors
include grade, resection margins, size, location, histologic type, and previous
treatment, with grade and margins being the most important. Tumor types
classified as STS that differ slightly in their presentation or treatment,
including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine
associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating
disease to treat, but adherence to solid surgical oncology principles can greatly
increase the odds of good disease control.
PMID- 9634351
TI - Principles of surgery for cancer palliation and treatment of metastases.
AB - Surgery in animals for palliation of clinical signs and treatment of cancer
metastases is becoming more popular. Patients must be selected carefully and
clear treatment goals established to maximize efficacy and minimize treatment
related morbidity and mortality. Palliative treatment is rendered primarily to
control clinical signs and secondarily to prolong life. Ironically,
metastasectomy is often performed with the intent to cure. For both
considerations, the clinician must be knowledgeable of the natural history of the
affecting neoplasia (i.e., how will the patient fare without treatment) and the
success rates and expected complications of the surgical procedures being
considered. Clinical guidelines for patient selection are presented and discussed
for palliative treatment and metastasectomy. Although data are available in the
human and veterinary medical literature to aid decision making, sound clinical
judgment remains most important for proper patient selection and care.
PMID- 9634352
TI - Principles of reconstructive surgery for the tumor patient.
AB - Small animal oncologic surgery is a relatively new and rapidly expanding field of
veterinary science. Many exciting and innovative techniques for surgical
resection of invasive tumors have been developed and published in the last
decade. Paralleling these developments have been major advancements in the
frontiers of reconstructive options to close the defects after major ablative
surgery. A more thorough understanding of the biologic behavior of tumors in our
patients has permitted us to rationally approach selected patients with high
doses of surgery with curative intent, palliation, or as part of a multimodality
treatment plan. Invasive oncologic procedures require thorough preoperative
planning and staging to accomplish the goal of tumor-free margins. Patient
factors, specifically tumor type, grade, anatomic location, and extent of local
invasion, will subsequently dictate the appropriate resection and reconstructive
options available. Resection of the tumor with a wide margin of normal tissue is
the surgeon's primary objective. The reconstructive phase of the surgery
endeavors to restore functional and cosmetic integrity to the regional anatomy.
Each resection and reconstruction procedure must be customized for the patient's
disease. Thoughtful preoperative planning, timing, and intraoperative flexibility
to unforeseen circumstances will minimize complications. Armed with a number of
reconstructive options for each case, the surgeon develops intraoperative
flexibility and latitude to be more aggressive during the primary resection. If
the surgeon self-imposes limitations on the aggressive removal of the primary
tumor by virtue of tissue closure concerns, the completeness of resection and
patient survival may well be jeopardized. As familiarity and experience with
different reconstructive options increases, the surgeon will have greater
confidence in removing large volumes of diseased tissue.
PMID- 9634353
TI - Airway Inflammation and Remodelling in Asthma: Implications for Asthma Therapy.
Proceedings of a workshop. Quebec City, Canada, March 29-30, 1996.
PMID- 9634354
TI - Veterinary education enters the university.
PMID- 9634355
TI - Researchers discover likely link between human, canine gene and blindness.
PMID- 9634356
TI - Characteristics of the febrile response in Pekin ducks.
AB - We measured body temperature in Pekin ducks for 22 h after intravenous injection
of the lipopolysaccharide (LPS) of gram negative bacteria at doses of 0, 1, 10,
and 100 micrograms.kg body mass (-1). The ducks developed monophasic fevers
showing increases in peak temperature reached and duration of fever with
increases in dose of LPS. Body temperatures of unrestrained telemetered ducks
without access to food and water were similar to those of saline-injected
controls in the fever experiments, but were lower in the morning than when the
same birds had access to food and water. This nocturnal hypothermia may have
resulted from energy restriction imposed by lack of food and water. The dose of
LPS required to elicit a fever of over 18 h duration (100 micrograms.kg-1) will
elicit a biphasic fever of 5 h duration in rats. Pekin ducks did not exhibit
biphasic fever even at the highest LPS dose administered, indicating that while
fever is superficially similar in the two homeothermic classes, there may be
differences in details of the mechanism. The similarities of the dose/response
characteristics to that of mammals lends support to the theory that fever in
vertebrates has a common phyletic origin.
PMID- 9634357
TI - 4th Conference of the Federation of Infection Societies. Manchester, United
Kingdom, November 26-28, 1997. Abstracts.
PMID- 9634358
TI - Retraction: A rabbit model for human cytomeglovirus--induced chorioretinal
disease (J Infect Dis 1993;168:336-44).
PMID- 9634359
TI - Retraction.
PMID- 9634360
TI - [Clinical study on azithromycin in 10% fine granules and 100mg capsules in the
field of pediatrics].
AB - Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100
mg capsules was given to pediatric patients to treat various infections. The
following results were obtained in our studies of AZM for its antibacterial
activities against clinical isolates, its pharmacokinetics, its efficacy, and its
safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were
determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive
cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus
aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes
(11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus
pneumoniae (10 strains). These MICs were similar to those of the other
macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml
against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13
micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml
against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against
salmonella sp. (1 strain). These values were similar to or lower than those of
the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or =
0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed
tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC
than AZM against this organism. 2. Plasma samples were collected from five
patients receiving fine granules and four patients receiving capsules for drug
level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg
body weight once daily for 3 days. Drug concentrations in plasma at two hours
after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine
granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3.
Urine samples were collected from four patients receiving fine granules and four
patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at
post-treatment 48 hours for fine granules and post-treatment 72 hours for
capsules. Urinary excretion rates of AZM in three patients on capsules lied in a
range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was
evaluated in 128 patients having a total of 19 different infections. AZM was
rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6,
resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was
evaluated in 23 patients with five different infections. AZM was found
"excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of
100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different
bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different
bacteria. 6. As for adverse reactions, one patient complained of eruption, one
vomiting, one loose stool, five diarrhea, when administered with fine granular
form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7.
As for abnormal laboratory changes, three patients were found with decreased WBC,
seven with increased eosinophil, two with increased GOT and GPT, one with
increased GPT. They were all on fine granular form of AZM. As far as
abnormalities found in patients administered with AZM in capsular form, two
showed decreased WBC, one decreased WBC along with increased eosinophil, and
three increased eosinophil.
PMID- 9634361
TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 19-1998. A 70-year-old man with diarrhea, polyarthritis, and a
history of Reiter's syndrome.
PMID- 9634362
TI - Computed tomography of the appendix.
PMID- 9634363
TI - Computed tomography of the appendix.
PMID- 9634364
TI - Computed tomography of the appendix.
PMID- 9634365
TI - Estimates of the probability of death from burn injuries.
PMID- 9634366
TI - Estimates of the probability of death from burn injuries.
PMID- 9634367
TI - X-linked Wiskott-Aldrich syndrome in a girl.
PMID- 9634368
TI - X-linked Wiskott-Aldrich syndrome in a girl.
PMID- 9634369
TI - Suicides after natural disasters.
PMID- 9634370
TI - Dyslexia.
PMID- 9634371
TI - Dyslexia.
PMID- 9634372
TI - Dyslexia.
PMID- 9634373
TI - Dyslexia.
PMID- 9634374
TI - Acute hepatic porphyrias and primary liver cancer.
PMID- 9634375
TI - 7th Annual Summer Neuropeptide Conference. Key West, Florida, USA. June 22-26,
1997. Abstracts.
PMID- 9634376
TI - Proceedings of the Terry Cutress Symposium. Dunedin, 28 August 1997. Part I.
PMID- 9634377
TI - Malignant neoplasms metastatic to gingivae.
AB - Malignant neoplasms metastatic to the gingivae are rare. Our review of the
literature revealed only eight acceptable examples. We are reporting two
additional cases. One patient was a 58-year-old man with an adenocarcinoma of the
lung which metastasized bilaterally to the maxillary gingiva. The second patient
was a 27-year-old man with a synovial sarcoma which metastasized to multiple
sites in the maxillary and mandibular gingiva. Clinically, gingival metastatic
lesions are most often confused with hemangioma, pyogenic granuloma, giant-cell
granuloma, and pepripheral fibroma. They usually occur late in the course of the
disease and are associated with metastatic deposits in many other organs and
tissues. Death usually occurs in a few weeks or months after discovery of the
gingival metastasis.
PMID- 9634378
TI - [Remembering Professor Kamillo Vidakovits, M.D., first director of the Surgical
Clinic of the Szeged Medical University].
PMID- 9634380
TI - [Bone metastases I].
PMID- 9634379
TI - [In memory of Dezso Hosz].
PMID- 9634381
TI - Proceedings of the 14th Pfefferkorn Conference. Belleville, Illinois, USA. August
6-11, 1995.
PMID- 9634382
TI - ["Our problem will no doubt be to face the demand". Interview by Roger D. Weill].
PMID- 9634383
TI - [Gene technology and dentistry].
PMID- 9634384
TI - [The modern practice team. The prophylaxis assistant, dental hygienist and the
dentist--organizational recommendations for practice].
PMID- 9634385
TI - [SwiDent--to whom is this insurance of use? The thoughts of a woman dental
practitioner after the risk assessment seminar of 13 March 1998].
PMID- 9634386
TI - [SwiDent does not work out for the patient].
PMID- 9634387
TI - [Involvement in the interests of youth. The dental health study of the Solothurn
Dentists Society].
PMID- 9634388
TI - [Esthetics in implantology. "Esthetic Perfection in Oral Implantology"--the
course of 17 to 18 October 1997 in Zurich].
PMID- 9634389
TI - Radiocarbon dates of Kennewick Man.
PMID- 9634390
TI - Research on auditory cortex plasticity.
PMID- 9634391
TI - One infant's memory of Oedipus.
PMID- 9634392
TI - One infant's memory of Oedipus.
PMID- 9634393
TI - AIDS office head picked.
PMID- 9634394
TI - Funders reassure genome sequencers.
PMID- 9634395
TI - Groups vie for space chimp colony.
PMID- 9634396
TI - WHO's slow road to funding reform.
PMID- 9634397
TI - EU ends 10-year battle over biopatents.
PMID- 9634398
TI - Taiwan trolls for U.S. firms to help it create an industry.
PMID- 9634399
TI - Building a better aspirin.
PMID- 9634400
TI - Antibodies stage a comeback in cancer treatment.
PMID- 9634401
TI - The salt of Europa.
PMID- 9634402
TI - Kinases and phosphatases--a marriage is consummated.
PMID- 9634403
TI - Challenges for European biology.
PMID- 9634404
TI - The ethics of AIDS vaccine trials.
PMID- 9634405
TI - The ethics of AIDS vaccine trials.
PMID- 9634406
TI - The ethics of AIDS vaccine trials.
PMID- 9634407
TI - Astrobiology institute picks partners.
PMID- 9634408
TI - Panel issues plea to boost FDA research.
PMID- 9634409
TI - Solving the brain's energy crisis.
PMID- 9634410
TI - New clues to alcoholism risk.
PMID- 9634411
TI - Growing joints use their noggins.
PMID- 9634412
TI - New method churns out TB mutants.
PMID- 9634413
TI - Obesity: how big a problem?
PMID- 9634414
TI - As obesity rates rise, experts struggle to explain why.
PMID- 9634415
TI - Uncoupling proteins provide new clue to obesity's causes.
PMID- 9634416
TI - Cloning for profit.
PMID- 9634417
TI - What's the best sound?
PMID- 9634418
TI - More deafness genes.
PMID- 9634419
TI - 6th International Limb Development and Regeneration Conference. Sun Valley,
Idaho, USA. 1998. Abstracts.
PMID- 9634420
TI - Radiotherapy at the End of the 20th Century: Current Role and Future Perspectives
in Clinical Oncology. Milano, Italy, 31 March-2 April 1998.
PMID- 9634421
TI - On the 60th anniversary of the dismissal of Jewish Faculty members from the
Vienna Medical School. Conferences held in Austria in 1998.
PMID- 9634422
TI - Histologic processing of thick tissue specimens from cytology slides.
PMID- 9634423
TI - Guidelines for Clinical Evaluation, Development, and Regulation of Lipid-Acting
Anti-Atherosclerosis Agents.
PMID- 9634424
TI - Images in neuroscience. Brain development, III. Cerebral cortex.
PMID- 9634425
TI - Predictors of systemic embolism in patients with mitral stenosis. A prospective
study.
AB - BACKGROUND: Most studies of the predictors of systemic embolism in patients with
mitral stenosis have been retrospective. OBJECTIVE: To prospectively study
factors associated with systemic embolism in mitral stenosis. DESIGN: Prospective
cohort study. SETTING: University-affiliated medical institution with 3000 beds.
PATIENTS: 534 consecutive patients with a mitral valve area of 2.0 cm2 or less;
132 patients were in sinus rhythm, and 402 were in atrial fibrillation.
MEASUREMENTS: Nine clinical and 10 echocardiographic variables were assessed for
prediction of systemic embolism over a mean (+/- SD) follow-up of 36.9 +/- 22.5
months. Diagnosis of systemic embolism was based on symptoms and signs (sudden
onset of peripheral arterial ischemic or neurologic manifestations without
prodromes) and on findings on computed tomography, angiography, and surgery.
RESULTS: For patients in sinus rhythm, age (relative risk [RR], 1.12 [95% CI,
1.04 to 1.21]), the presence of a left atrial thrombus (RR, 37.1 [CI, 2.82 to
487.8]), mitral valve area (RR, 16.9 [CI, 1.53 to 187.0]), and the presence of
significant aortic regurgitation (RR, 22.4 [CI, 2.72 to 184.8]) were positively
associated with embolism. For patients in atrial fibrillation, previous embolism
(RR, 3.11 [CI, 1.66 to 5.85]) was positively associated with embolism;
percutaneous balloon mitral commissurotomy (RR, 0.37 [CI, 0.18 to 0.79]) was a
negative predictor. CONCLUSIONS: It may be prudent to give anticoagulants not
only to patients in atrial fibrillation and patients with previous systemic
embolism but also to those showing a left atrial thrombus or significant aortic
regurgitation on echocardiography. Early percutaneous balloon mitral
commissurotomy may also help prevent systemic embolism in patients with mitral
stenosis.
PMID- 9634426
TI - Diagnostic yield and optimal duration of continuous-loop event monitoring for the
diagnosis of palpitations. A cost-effectiveness analysis.
AB - BACKGROUND: Continuous-loop event recorders are widely used for the evaluation of
palpitations, but the optimal duration of monitoring is unknown. OBJECTIVE: To
determine the yield, timing, and incremental cost-effectiveness of each week of
event monitoring for palpitations. DESIGN: Prospective cohort study. PATIENTS:
105 consecutive outpatients referred for the placement of a continuous-loop event
recorder for the evaluation of palpitations. MEASUREMENTS: Diagnostic yield,
incremental cost, and cost-effectiveness for each week of monitoring. RESULTS:
The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per
patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per
patient in week 3 and beyond. Over time, the cost-effectiveness ratio increased
from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and
$5832 per new diagnosis in week 3. CONCLUSIONS: In patients referred for
evaluation of palpitations, the diagnostic yield of continuous-loop event
recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring
period is reasonably cost-effective for most patients and should be the standard
period for continuous-loop event recording for the evaluation of palpitations.
PMID- 9634427
TI - Increased risk for cancer in patients with the Peutz-Jeghers syndrome.
AB - BACKGROUND: Some reports describe an increased risk for cancer in patients with
the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a
large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective
cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz
Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996.
MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up.
RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10
cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the
use of SEER (Surveillance, Epidemiology, and End Results) data for comparison,
the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the
Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P =
0.001). In women, the relative risk for breast and gynecologic cancer was 20.3
(CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an
increased risk for cancer. The relative risk for breast and gynecologic cancers
is particularly high.
PMID- 9634428
TI - Family history of colorectal adenomatous polyps and increased risk for colorectal
cancer.
AB - BACKGROUND: The risk for colorectal cancer among family members of patients with
colorectal cancer is well established, but the risk among family members of
patients with colorectal adenomas is less well established. OBJECTIVE: To examine
the risk for colorectal cancer among first-degree relatives of patients with
adenoma compared with that among first-degree relatives of controls without
adenoma. DESIGN: Reconstructed cohort study. SETTING: Three university-based
colonoscopy practices in New York City. PATIENTS: 1554 first-degree relatives of
244 patients with newly diagnosed adenomas and 2173 first-degree relatives of 362
endoscopically normal controls. MEASUREMENTS: Structured interviews were used to
obtain family history. Adjusted relative risks (RR) were estimated from Cox
proportional hazards regression models. RESULTS: The risk for colorectal cancer
was elevated (RR, 1.74 [95% CI, 1.24 to 2.45]) among first-degree relatives of
patients with newly diagnosed adenomas compared with the risk among first-degree
relatives of controls. This increased risk was the same for parents (RR, 1.58
[CI, 1.07 to 2.34]) and siblings (RR, 1.58 [CI, 0.81 to 3.08]). First-degree
relatives of patients with adenomas did not have elevated risk for other cancers.
The risk for colorectal cancer among family members increased with decreasing age
at diagnosis of adenoma in probands. Among first-degree relatives of patients who
were 50 years of age or younger when the adenoma was diagnosed, the risk was more
than four times greater (RR, 4.36 [CI, 2.24 to 8.51]) than that among first
degree relatives of patients who were older than 60 years of age when the adenoma
was diagnosed. CONCLUSIONS: First-degree relatives of patients with newly
diagnosed adenomas, particularly of patients who are 50 years of age or younger
at diagnosis, are at increased risk for colorectal cancer and should undergo
screening similar to that recommended for relatives of patients with colorectal
cancer.
PMID- 9634429
TI - Multiple concurrent reverse transcriptase and protease mutations and multidrug
resistance of HIV-1 isolates from heavily treated patients.
AB - BACKGROUND: Drug resistance of HIV-1 is an obstacle to the long-term efficacy of
antiretroviral therapy. OBJECTIVE: To characterize reverse transcriptase and
protease genes of multidrug-resistant HIV-1 isolates. DESIGN: Descriptive case
series. SETTING: Academic medical center. PATIENTS: Four consecutive patients
with HIV-1 infection were selected because they had previously received many
antiretroviral drugs and had not achieved plasma HIV-1 RNA suppression despite
treatment with several three-drug combinations. MEASUREMENTS: Reverse
transcriptase sequencing, protease sequencing, and drug susceptibility testing of
HIV-1. RESULTS: Isolates of HIV-1 from the four patients shared seven protease
mutations and eight reverse transcriptase mutations. These mutations were present
in biological clones and at three time points in three of the patients.
Susceptibility testing showed high-level resistance (30-fold to >100-fold) to
zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level
resistance (3-fold to 5-fold) to didanosine, zalcitabine, and stavudine.
CONCLUSIONS: Simultaneous resistance to almost all available antiretroviral drugs
may occur in HIV-1. The concordance and persistence of mutations in drug
resistant HIV-1 isolates suggest that some combinations of reverse transcriptase
and protease mutations give the virus a selective advantage in the presence of
various drug combinations.
PMID- 9634431
TI - Market influences on internal medicine residents' decisions to subspecialize.
AB - BACKGROUND: Managed care reduces the demand for internal medicine subspecialists,
but little empirical information is available on how increasing managed care may
be affecting residents' training choices. OBJECTIVE: To determine whether
increased managed care penetration into an area where residents train was
associated with a decreased likelihood that residents who completed general
internal medicine training pursued subspecialty training. DESIGN: Secondary
logistic regression analysis of data from the 1993 cohort of general internal
medicine residents. SETTING: U.S. residency training sites. PARTICIPANTS: 2263
U.S. medical school graduates who completed general internal medicine residency
training in 1993. MEASUREMENTS: The outcome variable (enrollment in subspecialty
training) was derived from the Graduate Medical Education Tracking Census of the
Association of American Medical Colleges (AAMC). Health maintenance organization
(HMO) penetration (possible range, 0.0 to 1.0; higher values indicate greater
penetration) was taken from the Interstudy Competitive Edge Database. Individual
and medical school covariates were taken from the AAMC's Student and Applicant
Information Management System database and the National Institutes of Health
Information for Management Planning, Analysis, and Coordination system. The U.S.
Census division was included as a control covariate. RESULTS: 980 participants
(43%) enrolled in subspecialty training. Logistic regression analyses indicated a
nonlinear association between managed care penetration into a training area and
the odds of subspecialization. Increasing managed care penetration was associated
with decreasing odds of subspecialization when penetration exceeded 0.15. The
choice of subspecialty training increased as HMO penetration increased from 0 to
0.15. CONCLUSIONS: Local market forces locally influenced the career decisions of
internal medicine residents, but the influence was small compared with the
effects of age and sex. These results suggest that market forces help to achieve
more desirable generalist-to-specialist physician ratios in internal medicine.
PMID- 9634430
TI - Nodular cutaneous microsporidiosis in a patient with AIDS and successful
treatment with long-term oral clindamycin therapy.
AB - BACKGROUND: In AIDS, nodular skin disease can result from various causes.
OBJECTIVE: To report a new manifestation of microsporidial infection presenting
as nodular skin disease with underlying osteomyelitis. DESIGN: Case report.
SETTING: Tertiary-care military medical center in Washington, D.C. PATIENT: A 36
year-old woman with late-stage AIDS who presented with disseminated, nodular
cutaneous lesions and underlying osteomyelitis. MEASUREMENTS: Disseminated
microsporidial infection with an Encephalitozoon-like species was diagnosed by
electron microscopic examination of material obtained from the skin lesions.
INTERVENTION: The patient received long-term oral clindamycin therapy, which
cured her disseminated infection. CONCLUSIONS: Microsporidia can cause
disseminated cutaneous infections in AIDS patients. The response of this patient
to long-term clindamycin therapy merits further evaluation.
PMID- 9634432
TI - Epidemiology of human rabies in the United States, 1980 to 1996.
AB - PURPOSE: To summarize the epidemiologic, diagnostic, and clinical features of the
32 laboratory-confirmed cases of human rabies diagnosed in the United States from
1980 to 1996. DATA SOURCES: Data were obtained from case reports of human rabies
submitted to the Centers for Disease Control and Prevention by state or local
health authorities. STUDY SELECTION: All cases of human rabies reported in the
United States from 1980 to 1996 in which infection with rabies virus was
confirmed by laboratory studies. DATA EXTRACTION: Patients were reviewed for
demographic characteristics, exposure history, rabies prophylaxis, clinical
presentation, treatment, clinical course, diagnostic laboratory tests,
identification of rabies virus variants, and the number of medical personnel or
family members who required postexposure prophylaxis after coming in contact with
an exposed person. DATA SYNTHESIS: 32 cases of human rabies were reported from 20
states. Patients ranged in age from 4 to 82 years and were predominantly male
(63%). Most patients (25 of 32) had no definite history of an animal bite or
other event associated with rabies virus transmission. Of the 32 cases, 17 (53%)
were associated with rabies virus variants found in insectivorous bats, 12 (38%)
with variants found in domestic dogs outside the United States, 2 (6%) with
variants found in indigenous domestic dogs, and 1 (3%) with a variant found in
indigenous skunks. Among the 7 patients with a definite exposure history, 6 cases
were attributable to dog bites received in foreign countries and 1 was
attributable to a bat bite received in the United States. In 12 of the 32
patients (38%), rabies was not clinically suspected and was diagnosed after
death. In the remaining 20 cases (63%), the diagnosis of rabies was considered
before death and samples were obtained specifically for laboratory confirmation a
median of 7 days (range, 3 to 17 days) after the onset of clinical signs. Of the
clinical differences between patients in whom rabies was diagnosed before death
and those in whom it was diagnosed after death, the presence of hydrophobia or
aerophobia was significantly associated with antemortem diagnosis (odds ratio,
11.0 [95% CI, 1.05 to 273.34]). The median number of medical personnel or
familial contacts of the patients who received postexposure prophylaxis was 54
per patient (range, 4 to 179). None of the 32 patients with rabies received
postexposure prophylaxis before the onset of clinical disease. CONCLUSIONS: In
the United States, human rabies is rare but probably underdiagnosed. Rabies
should be included in the differential diagnosis of any case of acute, rapidly
progressing encephalitis, even if the patient does not recall being bitten by an
animal. In addition to situations involving an animal bite, a scratch from an
animal, or contact of mucous membranes with infectious saliva, postexposure
prophylaxis should be considered if the history indicates that a bat was
physically present, even if the person is unable to reliably report contact that
could have resulted in a bite. Such a situation may arise when a bat bite causes
an insignificant wound or the circumstances do not allow recognition of contact,
such as when a bat is found in the room of a sleeping person or near a previously
unattended child.
PMID- 9634433
TI - Mosquitoes and mosquito repellents: a clinician's guide.
AB - This paper is intended to provide the clinician with the detailed and scientific
information needed to advise patients who seek safe and effective ways of
preventing mosquito bites. For this review, clinical and analytical data were
selected from peer-reviewed research studies and review articles, case reports,
entomology texts and journals, and government and industry publications. Relevant
information was identified through a search of the MEDLINE database, the World
Wide Web, the Mosquito-L electronic mailing list, and the Extension Toxicology
Network database; selected U.S. Army, U.S. Environmental Protection Agency, and
U.S. Department of Agriculture publications were also reviewed. N,N-diethyl-3
methylbenzamide (DEET) is the most effective, and best studied, insect repellent
currently on the market. This substance has a remarkable safety profile after 40
years of worldwide use, but toxic reactions can occur (usually when the product
is misused). When DEET-based repellents are applied in combination with
permethrin-treated clothing, protection against bites of nearly 100% can be
achieved. Plant-based repellents are generally less effective than DEET-based
products. Ultrasonic devices, outdoor bug "zappers," and bat houses are not
effective against mosquitoes. Highly sensitive persons may want to take oral
antihistamines to minimize cutaneous reactions to mosquito bites.
PMID- 9634434
TI - Letter from Reykjavik.
AB - Medical care in Iceland can be viewed as an experiment of nature. This small
island society has combined the Nordic social and welfare structures with
advanced international medicine. The Vikings settled Iceland in the ninth
century, and the population has remained biologically homogeneous because of its
remote isolation. This homogeneity may provide a unique opportunity to contribute
to the understanding of the genetics of common disorders. Iceland's isolation has
also limited the resources that are available for clinical training. Therefore,
it has been necessary for most physicians who graduate from the medical school at
the University of Iceland to obtain postgraduate training abroad. This has been
of enormous benefit to Icelandic medicine. Fewer opportunities for foreign
medical graduates to train in the United States would have a substantial effect
on the future practice of Icelandic medicine. The Icelandic health care system
faces many challenges. Because health care spending has been reined in,
priorities must be set more clearly than in the past, and heated discussions have
erupted about gatekeeping and merging of hospitals. These have been "interesting
times" for Icelandic medicine. Other countries may learn lessons from our medical
situation: a microcosm, to be sure, but no longer an isolated one.
PMID- 9634435
TI - What's new in transplant immunology: problems and prospects.
AB - In the past 40 years, transplantation has moved from an experimental form of
therapy used almost exclusively for renal failure to an accepted treatment for
end-stage kidney disease, heart disease, liver disease, lung disease, and
diabetes mellitus. Tissue transplantation for conditions from thermal injury to
Parkinson disease is being investigated. The primary barrier in transplantation
medicine is the immunologic reaction of the recipient to donor organs and
tissues. Currently available drugs permit excellent short-term graft survival but
have not led to reliable long-term survival. Recent advances in the understanding
of this immune response have suggested new approaches to induction of immunologic
tolerance and reduction of late graft losses. Because of the excellent short-term
success of current agents, integration of these new approaches into clinical
trials is challenging and raises important questions about the design of such
trials.
PMID- 9634436
TI - On the death of house officers.
PMID- 9634437
TI - Resisting resistance: maximizing the durability of antiretroviral therapy.
PMID- 9634438
TI - Death in springtime.
PMID- 9634439
TI - Interferon-alpha in chronic hepatitis C.
PMID- 9634440
TI - Successful treatment of hyperammonemia after lung transplantation.
PMID- 9634441
TI - Adult (not internal) medicine.
PMID- 9634442
TI - Adult (not internal) medicine.
PMID- 9634443
TI - Adult (not internal) medicine.
PMID- 9634444
TI - Adult (not internal) medicine.
PMID- 9634445
TI - Adult (not internal) medicine.
PMID- 9634446
TI - Adult (not internal) medicine.
PMID- 9634447
TI - Literature and medicine: an on-line guide.
PMID- 9634448
TI - Immunologic Diseases of the Ear. Conference proceedings. Positano, Italy, October
24-26, 1996.
PMID- 9634449
TI - Frontiers of Neurology: A Symposium in Honor of Fred Plum. New York City, New
York, USA. October 5, 1996.
PMID- 9634450
TI - Salivary Gland Biogenesis and Function. Proceedings of a conference. Arlie,
Virginia, USA. November 7-10, 1996.
PMID- 9634451
TI - Health care report cards.
PMID- 9634452
TI - Fetal surgery: a brief review.
AB - Fetal therapy is a logical extension of fetal diagnosis. Fetal surgery has been
performed in humans for the past 10 years. During this time, technical obstacles
have been overcome and the natural history of many fetal disorders has been
defined. A select group of disorders amenable to potential improvement by fetal
treatment has been identified including fetal urinary tract obstruction, fetal
diaphragmatic hernia, fetal congenital cystic adenomatoid malformation and fetal
sacrococcygeal teratoma. The fetal surgical experience with each of these lesions
is reviewed and the maternal risk of fetal surgery is discussed.
PMID- 9634453
TI - CT findings in neonatal hypothermia.
AB - BACKGROUND: Newborn infants are particularly prone to hypothermia, a condition
with a high mortality. OBJECTIVE: To study the CT brain patterns in infants with
hypothermia and neurological symptoms. MATERIALS AND METHODS: We reviewed the
brain CT of nine infants with neonatal hypothermia, multiple organ failure,
seizures and coma. RESULTS: Two infants had normal CT scans, acutely and at
follow-up, and were clinically normal at follow-up. In seven infants, CT showed
diffuse cerebral oedema, with reversal of the normal density relationship between
grey and white matter and a relative increased density of the thalami, brainstem
and cerebellum - the 'reversal sign'. In six surviving infants with severe
developmental delay, follow-up CT revealed cerebral atrophy with multicystic
encephalomalacia. CONCLUSIONS: The 'reversal sign' has been described in the
abused child, birth asphyxia and anoxia due to drowning. Neonatal hypothermia is
offered as a further cause.
PMID- 9634454
TI - Renal excretion of gadolinium mimicking calculi on non-contrast CT.
PMID- 9634455
TI - Ultrasonography in the study of salivary gland lesions in children.
AB - Salivary gland lesions are uncommon in children and may be related to the
parotid, submandibular or sublingual glands. Inflammatory lesions are the most
common cause of salivary gland abnormalities in children and can be due to acute
viral, acute suppurative, or recurrent acute or chronic inflammation.
Intraparotid lymphadenitis may also occur, as in cat-scratch disease or in other
causes of cervical lymphadenitis. Salivary gland neoplasms are rare in children,
and most of them are benign including mainly hemangioma, pleomorphic adenoma, or
lymphangioma. Other lesions, such as sialolithiasis, mucocele, or ranula, may
also be seen. Ultrasonography should be the initial imaging study used for the
examination of salivary gland lesions in children, given the fact that most of
such lesions are benign and are shown up clearly by sonography. In most cases,
this technique permits the differentiation of intraglandular and extraglandular
lesions, and may suggest the correct diagnosis. The entire lesion could not be
totally depicted by US however, and other imaging techniques such as CT or MRI
may be necessary. Vascular lesions can be demonstrated more clearly through the
use of color Doppler imaging. Some of the lesions may appear similar, and
clinical correlation is important for the differential diagnosis. This article
discusses the sonographic appearance and clinical manifestations of the spectrum
of salivary gland abnormalities that may occur in children.
PMID- 9634456
TI - Preamputation MR imaging in meningococcemia and comparison to conventional
arteriography.
AB - Meningococcemia is a life-threatening infection which produces purpura fulminans
and extremity gangrene in its most severe form. In patients with gangrene,
amputation is usually necessary. The amputations frequently need revision as
ischemic changes in the underlying soft tissues and bone are difficult to
evaluate at the time of surgery. These ischemic changes often have non-vascular
distributions and progress over time. We present two patients in whom MR imaging
and MR angiography were performed prior to planned amputation. These cases
demonstrate the potential utility of MR imaging in this setting, and compare the
MR angiographic results to conventional arteriography in one of these patients.
PMID- 9634457
TI - Pyloric muscle in asymptomatic infants: sonographic evaluation and discrimination
from idiopathic hypertrophic pyloric stenosis.
AB - OBJECTIVE: To compare the morphological and functional US appearance of the
pylorus in healthy infants with those suffering from idiopathic hypertrophic
pyloric stenosis (IHPS) in order to determine the pathological limits and to find
out the most discriminating morphometric parameter. MATERIALS AND METHODS: The
pylorus of 84 asymptomatic infants was prospectively evaluated with respect to
morphology (pyloric length, pyloric diameter, muscle thickness and pyloric
volume) and function (gastric peristalsis and emptying, pyloric opening and the
fluid passage). Results were compared with 85 patients with proven IHPS. RESULTS:
In every normal infant we observed frequent pyloric opening with passage of
gastric contents and quick gastric emptying. All infants with proven IHPS
presented with a permanently closed pylorus and exaggerated, retrograde gastric
peristalsis. For each of the four parameters, highly significant differences (P <
0.0001) were found between the control and IHPS groups. Pathological limits were
3 mm for muscle thickness (accuracy 100 %), 15 mm for pyloric length (accuracy 94
%), 11 mm for pyloric diameter (accuracy 92 %) and 12 ml for pyloric volume
(accuracy 96 %). CONCLUSIONS: Evaluation of pyloric function plays an important
role in the diagnosis of IHPS. The morphometric parameters are highly accurate in
differentiating IHPS from a normal pylorus, muscle thickness being the most
discriminating parameter.
PMID- 9634458
TI - US, CT and MR imaging characteristics of nephroblastomatosis.
AB - OBJECTIVES: To describe the imaging features of nephroblastomatosis with US, CT
and MR, to point out characteristics of differentiation between nephrogenic rests
(NR) and Wilms' tumour (WT) and to determine the most appropriate imaging
modality. MATERIALS AND METHODS: We reviewed the US, CT and MR images of 29 cases
of histopathologically confirmed nephroblastomatosis sent to our department for
reference evaluation (German nephroblastoma study). The series included 17
kidneys with NR, 6 kidneys with WT and 32 kidneys with both NR and WT. RESULTS:
NR presented as multinodular, peripheral, cortical lesions, the diffuse form of
distribution being less common. Foci were homogeneous and of low echogenicity,
density or signal intensity. The lesions were most clearly depicted with contrast
enhanced CT and T1-weighted (T1-W) MR images. Lesions smaller than 1 cm were
rarely identified by US. The most reliable criterion to differentiate NR from WT
was their homogeneity. CONCLUSIONS: Contrast-enhanced CT and T1-W MR images are
of similar potential and superior to US in the diagnosis of nephroblastomatosis.
Due to the significant radiation dose of serial CT, MR imaging should be the
method of choice wherever it is available. The cost-effectiveness and
availability of US makes it ideal for serial follow-up of known lesions.
PMID- 9634459
TI - Outcome of residual mediastinal masses of thoracic lymphomas in children: impact
on management and radiological follow-up strategy.
AB - BACKGROUND: Following treatment with chemotherapy and radiotherapy, patients with
thoracic lymphomas may demonstrate benign residual mediastinal masses, composed
of inflammatory, fibrous or necrotic tissue. Because of the potential risk of
viable tumour cells within the mass, histological verification of the nature of
these masses may be requested. OBJECTIVE: To study the outcome of thoracic
lymphomas in children in order to optimise the radiological follow-up strategy of
residual mediastinal masses (RMM). MATERIALS AND METHODS: A retrospective study
of 39 children [24 with Hodgkin's disease (HD), 10 with non-Hodgkin's lymphoma
(NHL), and 5 with anaplastic lymphoma (AL)]. The results of chest X-rays (CXR)
and thoracic CT performed at the time of re-assessment were compared with the
histology of the residual masses (n = 11) or the clinical course (n = 28).
RESULTS: At the time of re-evaluation, 16/39 patients had residual mediastinal
enlargement (RME) on CXR, and 18/39 patients had RMM on CT. Good concordance was
observed between the two imaging modalities (K = 0.69). Two children with a RMM
died from extra-mediastinal progression. Two children with NHL had active
residual mediastinal lesions but neither had RMM. Sixteen cases of RMM were
observed in the remaining 35 children and 9 of these masses were histologically
verified as benign. A favourable course was observed in these 35 cases.
CONCLUSIONS: RMM are frequent and generally benign. They are well shown on CXR
and have a non-specific appearance on CT. Except when required by a treatment
protocol, they could be submitted to further radiological follow-up before
contemplating surgical verification.
PMID- 9634460
TI - Gallbladder contraction in biliary atresia: a pitfall of ultrasound diagnosis.
AB - In 3 (9 %) of 34 children with biliary atresia, US revealed gallbladder
contraction following an oral feed, given on admission, but not with subsequent
feeds. Surgery revealed a Kasai type IIIa biliary atresia with a patent
communication between the gallbladder and duodenum. We propose that the bile
ducts may initially have been patent, but then gradually became obliterated
secondary to inflammation. These cases may explain the development of one type of
biliary atresia.
PMID- 9634461
TI - Ossifying renal tumor of infancy presenting as a palpable abdominal mass.
AB - We report a case of ossifying renal tumor of infancy, which presented as a
palpable abdominal mass in an otherwise asymptomatic 10-month-old girl. The tumor
was partially calcified and occupied the renal pelvis, causing severe
hydronephrosis. The differential diagnosis for a patient this age included Wilms
tumor, extra-adrenal neuroblastoma, infection, calculus, calcified hematoma and
ossifying renal tumor of infancy. The child underwent heminephrectomy and is
currently doing well.
PMID- 9634462
TI - Ossifying renal cell carcinoma.
AB - In older children, ossifying renal cell carcinoma is a potential explanation for
a network of well-organized, curvilinear high-attenuation areas in a renal mass.
Since ossification of renal cell carcinoma is a favorable tumor marker that
implies a less extensive resection, it is important to anticipate this tumor
before surgical resection is undertaken.
PMID- 9634463
TI - Gastroduodenal intussusception with a gastric antral polyp.
PMID- 9634464
TI - US demonstration and diagnosis of the midaortic syndrome.
AB - The midaortic syndrome is a rare entity, typically presenting with hypertension,
refractory to treatment. The diagnosis is usually made by arteriography. We
report a child in whom the diagnosis was made by ultrasound, confirmed by
arteriography and successfully treated by balloon dilatation.
PMID- 9634465
TI - Head-wag autotomography of the upper cervical spine in infantile torticollis.
AB - BACKGROUND: Infants with torticollis require evaluation of the entire cervical
spine for vertebral anomalies as part of the work-up, but open-mouth views to
assess occiput to C2 are difficult to obtain. OBJECTIVE: To evaluate a "head wag"
autotomographic technique for the frontal projection of this region. MATERIALS
AND METHODS: Twenty infants under one year of age were evaluated using this
technique. RESULTS: Sixteen of 20 could be adequately evaluated using this
simple, low-radiation-dose procedure. CONCLUSION: For infants with torticollis in
whom vertebral anomalies need to be excluded, the "head wag" technique is useful.
PMID- 9634466
TI - Primary ovarian leiomyosarcoma in an adolescent following radiation for
medulloblastoma.
AB - Primary ovarian leiomyosarcomas are rare neoplasms of the ovary, particularly in
the pediatric population. Their occurrence following radiation therapy for
previous malignancy has important implications. We present a case of primary
ovarian leiomyosarcoma in an adolescent following therapy for medulloblastoma.
PMID- 9634467
TI - Cerebral MRI of very low birth weight children at 6 years of age compared with
the findings at 1 year.
AB - BACKGROUND: We have previously reported the results of cerebral MRI examinations
in an unselected year cohort of very low birth weight (VLBW) infants at one year
of corrected age. Twenty-one (78 %) of 27 infants had abnormal myelination,
mainly in the central occipital white matter (COWM) and in the centrum semiovale
(CS), seen on T2-weighted images. Twelve infants had irregular and dilated
lateral ventricles. We speculated whether these findings indicated perinatal
periventricular leukomalacia (PVL). Only two infants had completely normal MRI at
age 1 year. OBJECTIVE: To determine whether the abnormal myelination seen at 1
year of age, was still present, either as delayed myelination or as gliosis
caused by perinatal PVL. MATERIALS AND METHODS: In the present study, we report
the results of follow-up cerebral MRI in 20 of these infants at 6 years of age.
RESULTS: Most of the children with MRI deviations at 1 year still had
abnormalities at 6 years. Abnormal myelination in the central occipital white
matter combined with abnormalities in the CS or with ventricular dilatation at
age 1 year, presented as gliosis in 12 of 13 children at 6 years of age.
Abnormalities solely in the COWM at age 1 year had normalised in two of five
children and persisted as delayed myelination in three at age 6 years. Gliotic
changes in periventricular white matter were found in 12 of 20 children (60 %).
Areas most affected were the CS (11 children) and the COWM (9 children). Delayed
myelination in COWM was found in six children (30 %), combined with gliosis in CS
in three children. Twelve infants had ventricular dilatation both at 1 and 6
years of age. CONCLUSIONS: The MRI correlates of PVL, i. e. gliosis and
ventricular dilatation, are common findings on cerebral MRI at 6 years of age in
VLBW infants.
PMID- 9634468
TI - High-resolution US of non-traumatic recurrent dislocation of the peroneal
tendons: a case report.
AB - We report the case of a young girl with recurrent sharp pain in the outer aspect
of the ankle. She had no previous trauma. High-resolution US (HRUS) showed a
complete intermittent dislocation of the peroneal tendons. Post-traumatic chronic
peroneal instability is quite common, whereas complete dislocation is rare. HRUS
is an important adjunct to clinical examination and radiographic evaluation of
patients with musculoskeletal disorders of the foot and ankle [1]. This paper
reports its value in non-traumatic recurrent dislocation of the peroneal tendons.
PMID- 9634469
TI - Ilio-psoas abscess in the paediatric population: treatment by US-guided
percutaneous drainage.
AB - BACKGROUND: Image-guided percutaneous drainage has been shown to be a safe and
effective alternative to surgery in the management of psoas abscess in adults and
adolescents. There is little information on its use in children. OBJECTIVE: To
evaluate the safety and efficacy of US-guided percutaneous needle aspiration and
catheter drainage of ilio-psoas abscesses. MATERIALS AND METHODS: A retrospective
review of 14 children with 16 ilio-psoas abscesses (10 pyogenic and 4
tuberculous) who were treated by US-guided percutaneous needle aspiration (n = 5)
or catheter drainage (n = 9) along with appropriate antimicrobial therapy.
RESULTS: Percutaneous treatment was successful in 10 of the 14 patients; all
showed clinical improvement within 24-48 h of drainage and subsequent imaging
demonstrated resolution of the abscess cavities. Surgery was avoided in all of
these ten patients except one, who underwent open surgical drainage of
ipsilateral hip joint pus. Of the other four patients, two had to undergo
surgical drainage of the ilio-psoas abscesses after failure of percutaneous
treatment, one improved with antibiotics after needle aspiration failed to yield
any pus, and one died of continuing staphylococcal septicaemia within 24 h of the
procedure. There were no procedural complications. CONCLUSIONS: Percutaneous
drainage represents an effective alternative to surgical drainage as a supplement
to medical therapy in the management of children with ilio-psoas abscesses.
PMID- 9634470
TI - Dark spleens and livers on MRI after chemotherapy: is it really iron overload?
PMID- 9634471
TI - The MIBG super scan.
PMID- 9634472
TI - Complexity among constituents of the HLA-B*1501 peptide motif.
AB - Analysis of peptides derived from HLA class I molecules indicates that thousands
of unique peptides are bound by a single molecular type, and sequence examination
of the pooled constituents yields a motif which collectively defines the peptides
bound by a given class I molecule. Motifs resulting from pooled sequencing are
then used to infer whether particular viral and tumor protein fragments might
serve as class I-presented peptide therapeutics. Still undetermined from a pooled
motif is the breadth or range of peptides in the population which are brought
together to form the pooled motif, and it is therefore not yet known how
representative of the population a pooled motif is. By employing hollow fiber
bioreactors for large-scale production of HLA class I molecules, sufficient
peptides are produced to investigate individual subsets of peptides comprising a
motif. Edman sequencing and mass spectrometric analysis of peptides eluted from
HLA-B*1501 reveal that many peptide sequences fail to align with either the N- or
C-terminal anchors predicted for the B*1501 peptide motif through whole pool
sequencing. These analyses further reveal auxiliary anchors not previously
detected and peptides significantly larger and smaller than the predicted
nonamer, ranging from 6 to 12 amino acids in length. These results demonstrate
that constituents of the B*1501 peptide pool vary markedly in comparison with one
another and therefore in comparison with previously established B*1501 motifs,
and such complexity indicates that many of the peptide ligands presented to CTL
cannot be predicted using class I consensus motifs as search criteria.
PMID- 9634473
TI - The influence of exogenous peptide on beta2-microglobulin exchange in the HLA
complex: analysis in real-time.
AB - We used an optical biosensor to determine the relative binding affinity of
peptides to purified HLA class I molecules. In this assay we monitor beta2
microglobulin (beta2m) exchange within the HLA-A2 molecule, whereby native beta2m
in the complex is replaced by beta2m immobilized at the surface of the biosensor.
Quantitative kinetic measurements permit us to obtain association rate (kass),
dissociation rate (kdiss) and affinity constants (KA) for the beta2m exchange
reaction, alone, (control) and in the presence of exogenous peptide. We tested a
panel of six peptides which had been designed and synthesized with an HLA-A2
binding motif, and had also been tested by the T2-cell binding assay, along with
control peptides. The biosensor results demonstrate that exogenous peptide
influences the dynamics of beta2m exchange in a sequence-specific manner. Five of
six peptides increased the association rate, decreased the dissociation rate, and
significantly increased the affinity (KA=1. 55-1.88x10(9) M-1) of HLA-A2 for
immobilized beta2m compared with the control (KA =1.14+/-0.04x10(9)M-1),
demonstrating stabilization of the complex. One peptide was unable to stabilize
the complex, as also shown in the T2 binding assay. However, analysis of peptide
sequences demonstrated that the HLA-A2 secondary motif as well as primary motif
residues are required for HLA-A2 stabilization. Further experiments demonstrated
that beta2m exchange alone cannot stabilize the HLA class I complex at the cell
surface until a peptide of sufficient binding affinity is bound. Hence kinetics
equal to or below the control values in our biosensor assay probably represent an
unstable complex in vivo. Unlike other methods described for the analysis of
peptide stabilization, this approach is significantly faster, provides full
kinetic analysis, and is simpler, since it requires no labeling of peptides.
Furthermore, this may have important implications in the assessment of peptide
vaccines.
PMID- 9634474
TI - High RAD51 mRNA levels in young rabbit appendix. A role in B-cell gene
conversion?
AB - The rabbit has a limited number of VH genes that rearrange. As in the chicken,
the 3'-most VH1 gene is rearranged in most B lymphocytes. This laboratory
reported that by 6 weeks after birth, diversification of rearranged VH genes
occurs, at least in part, by gene conversion-like events in the appendix,
suggesting that this organ is a homologue of the avian bursa of Fabricius. Rad51
contributes to the repair of double-strand breaks in DNA during somatic and
meiotic recombination. The gene was first identified in lower eukaryotes, and
later in vertebrates including chicken, as encoding an Escherichia coli RecA-like
protein. We report the cloning and sequencing of RAD51 from the rabbit. Because
the chicken bursa was shown to express high levels of RAD51 message, we
investigated the expression of RAD51 in the rabbit appendix and other tissues.
Using a quantitative polymerase chain reaction mimic assay and conventional
northern analyses, we found high RAD51 expression in young rabbit appendix
comparable to levels in testis where there is an abundance of meiotic
recombination. RAD51 levels were three times higher in appendix B lymphocytes
compared with T lymphocytes and were lower in adult appendix, as well as in
spleen and Peyer's patches of young rabbits. We measured the levels of message in
several appendix cell sub-populations obtained by fluorescence-activated cell
sorting and found that sub-populations of B lymphocytes corresponding to
different stages of B-cell development as well as B cells undergoing isotype
switch did not have significantly different mRNA levels.
PMID- 9634475
TI - Regulation of expression of the human lymphocyte activation gene-3 (LAG-3)
molecule, a ligand for MHC class II.
AB - The lymphocyte activation gene-3 (LAG-3), a major histocompatibility complex
(MHC) class II ligand evolutionarily related to CD4, is expressed exclusively in
activated T and NK lymphocytes and seems to play a role in regulating the
evolving immune response. We first determined that surface LAG-3 expression on
activated human T cells is upregulated by certain cytokines (IL-2, IL-7, IL-12)
and not by others (IL-4, IL-6, IL-10, TNF-alpha, TNF-beta, IFN-gamma). Surface
LAG-3 expression correlated with intracellular IFN-gamma production in both CD4+
and CD8+ T-cell subsets. We then analyzed the 5' transcription control sequences
of LAG-3. A DNase I hypersensitive site induced in T cells following cellular
activation was found in the region including the transcriptional start site,
showing that DNA accessibility is a mechanism which restricts LAG-3 expression to
activated T cells. Transcription is initiated at three sites. A GC box, 80 base
pairs (bp) upstream of the major transcription start site, forms a minimal
promoter which is regulated by two upstream regions containing positive and
negative regulatory elements with multiple protein binding sites as shown by
footprinting analysis. In particular, a GATA/c-Ets motive was identified in a
short segment homologous to the mouse CD4 distal enhancer, suggesting that LAG-3,
which is embedded in the CD4 locus, may be controlled by some CD4 regulatory
elements. Finally, a 100 bp region downstream of the transcription start site was
shown to be involved in the cell-specific control of LAG-3 expression.
Understanding this highly regulated expression may help to determine the
intriguing role of this activation-induced MHC class II ligand.
PMID- 9634476
TI - Mice carrying a CD20 gene disruption.
AB - CD20 is a hallmark antigen of B lymphocytes. Its expression is restricted to
precursor and mature B cells but it is not expressed on plasma cells. The protein
is a membrane-embedded phosphoprotein that appears likely to transverse the
membrane four times. Its function is unknown although CD20 has been variously
proposed to play a role in B-cell activation, proliferation, and calcium
transport. A unique homologue of human CD20 has been described in mouse, which
also shows a B-cell-specific pattern of expression. Here we describe the
generating of mice carrying a CD20 gene disruption. So far, we have failed to
detect any major effect of the gene disruption on the differentiation and
function of B lymphocytes as judged by the expression of surface markers, antigen
receptor signaling, proliferative responses, or calcium uptake. We did note,
however, that the mice homozygous for the gene disruption [generated by
intercrossing (129 x C57BL/6)F1 CD20+/- heterozygotes] showed a substantial
depletion of the sub-population of peritoneal B cells that lack expression of the
B220 (RA3-6B2) isoform of CD45. The loss of the IgM+ 6B2- peritoneal B cells is
not, however, attributable to the CD20 gene disruption itself. Rather, it
segregates with a polymorphic difference between the 129 and C57BL/6 strains that
is linked to the CD20 locus which, intriguingly, is itself close to the CD5 gene.
This demonstrates that caution must be exercised when comparing the phenotypes of
F2 litter-mates generated from crosses between 129 embryonic stem-cell-derived
chimeras and mice of other strains.
PMID- 9634477
TI - beta2-Microglobulin in neotropical primates (Platyrrhini).
AB - Nucleotide sequences for the three exons of the beta2-microglobulin (beta2m) gene
(B2m) were determined for 135 animals representing 37 species and all 16 genera
of neotropical primates (Platyrrhini). Twenty-eight different nucleotide
sequences, encoding for 26 different proteins, were obtained. In comparison with
those of other primate species, the beta2-microglobulins of the Platyrrhini form
a distinct clade. Individual genera of neotropical primates have distinctive B2m
sequences, but within a genera species can have either the same or different B2m
sequences. B2m polymorphism was found within three of the species sampled:
Callicebus personatus, Saguinus midas, and Aotus azarae. Of these only the
polymorphism in A. azarae has an effect upon the mature, functional beta2m
protein: residue 4 being either alanine or threonine. The A. azarae B2m allele
encoding alanine at position 4 is shared with another species of Aotus (A.
infulatus). In pairwise comparison the mature beta2m proteins of neotropical
primates differ by 1-9 amino acid substitutions which can occur at 18 positions
within the sequence. The substitutions are distributed throughout the primary
structure but are more commonly found in loops rather than beta strands of the
tertiary structure. Of 17 residues of beta2m which hydrogen-bond with the class I
heavy chain in human MHC class I molecules, 13 are conserved in the neotropical
primates. The overall pattern of sequence variation in the B2m genes of the
Platyrrhini is consistent with an evolution by successive selectively neutral
events.
PMID- 9634478
TI - Linkage of RXRB-like genes to class I and not to class II Mhc genes in the
zebrafish.
PMID- 9634479
TI - Heterogeneity in the genetic basis of human complement C9 deficiency.
PMID- 9634480
TI - A new HLA-B15 allele (B*1541) found in a Mexican of Nahua (Aztec) descent.
PMID- 9634481
TI - Characterization of an HLA-A26 serologic variant.
PMID- 9634482
TI - The HLA-B* 1516 motif demonstrates HLA-B-specific P2 pocket characteristics.
PMID- 9634483
TI - Eight rat RT1Ba sequences.
PMID- 9634484
TI - Heterochronic differences of Hoxa-11 expression in Xenopus fore- and hind limb
development: evidence for lower limb identity of the anuran ankle bones.
AB - The wrist (carpus) and ankle (tarsus) of most tetrapods, as well as the wrist of
anurans, contains relatively small nodular skeletal elements. The anuran tarsus,
however, comprises a pair of long bones, the proximal tarsals tibiale and
fibulare, which resemble the lower leg bones, tibia and fibula (zeugopodium). In
this paper we investigate whether the proximal tarsals of Xenopus are of
zeugopodial character identity, i.e. whether they develop under the influence of
the same genes that pattern the lower limb. We compare Hoxa-11 expression in the
forelimb bud with that in the hind limb bud by whole-mount in situ hybridization.
Hoxa-11 has been implicated in the development of the lower limb. In Xenopus we
note three differences between Hoxa-11 expression in fore- and hind limb buds:
(1) Hoxa-11 expression is maintained until the hind limb bud reaches a larger
size (2 mm) than that of the forelimb bud (1.5 mm); (2) Hoxa-11 expression is
maintained over larger spatial domains than in the forelimb; and (3) Hoxa-11
expression has a pronounced posterior polarity in the hind limb, but not in the
forelimb. Hind limb expression of Hoxa-11 can be understood as a heterochronic
prolonging of the expression dynamic in the forelimb. Finally we found that the
proximal tarsals start to develop within the expression domain of Hoxa-11, while
in the forelimb the lower arm elements reach the distal expression limit of Hoxa
11. The gene expression data presented here support the notion of a zeugopodial
identity of the proximal tarsal elements in Xenopus.
PMID- 9634485
TI - Isolation and characterization of three mRNAs enriched in embryos of the direct
developing sea urchin Heliocidaris erythrogramma: evolution of larval ectoderm.
AB - The Australian sea urchin Heliocidaris erythro-gramma utilizes a derived direct
developmental mode that evolved 8-12 million years ago. From a differential
screen we have isolated a small set of cDNAs corresponding to genes more greatly
expressed in embryos of H. erythrogramma than in those of its indirect-developing
nearest relative, H. tuberculata. The method was biased towards abundant
transcripts and did not allow detection of modifications of usage of highly
conserved gene family members. Three differentially expressed abundant
transcripts were found that potentially encode secreted proteins. Two of these,
the arylsulfatase HeARS and the putative lectin HeEL-1, were identifiable as
homologues of known proteins. Another gene, HeET-1, may be exclusively expressed
in the H. erythrogramma embryo. In situ hybridization experiments demonstrate
that all three transcripts are localized to the ectoderm. Two of them, HeET-1 and
HeEL-1, are transcribed in an identical domain comprising the larval ectoderm.
This region of gene expression has acquired a novel columnar cytology during the
evolution of the H. erythrogramma embryo. The third sequence, HeARS, encodes an
arylsulfatase homologue. Its expression is uniform in the gastrula, but as the
rudiment develops it accumulates to the greatest extent in the invaginating
vestibular ectoderm. Through comparisons with indirect-developing species, we
show that this concentration of arylsulfatase mRNA in the rudiment is a novel
feature of H. erythrogramma development. These data suggest that H. erythrogramma
has a unique arrangement of ectodermal gene expression territories. We propose
that these reflect larval adaptations that have occurred in the lineage leading
to H. erythrogramma, and enabled the evolution of direct development.
PMID- 9634486
TI - Down-regulation of expression of a pupal cuticle protein gene by transcriptional
and posttranscriptional control mechanisms during metamorphosis in Galleria.
AB - Down-regulation of expression of a pupal cuticle protein gene (GmPCP52) was
investigated during metamorphosis in Galleria during normal development and in
response to 20-hydroxyecdysone (20 E) and a juvenile hormone analogue
(epofenonane). The developmental profile of GmPCP52 transcription was traced by
nuclear run-on transcription assays. Transcription of the GmPCP52 gene is highest
shortly after pupal ecdysis. There is a rapid decline between a pupal age of 12
and 18 h. Transcription becomes undetectable at 24 h. 20 E accelerates cessation
of transcription, but induces a short second period of GmPCP52 transcriptional
activity. Epofenonane prolongs transcription and induces a second round of
transcriptional activity in relation to the synthesis of a second pupal cuticle.
Analysis of changes in poly(A) tail length of GmPCP52 mRNA demonstrated control
of expression at the level of mRNA translatability and stability. At 6 to 9 h
poly(A) tails of GmPCP52 mRNA have lengths of 70 to 170 A-residues. From 9 h on
mRNA with about 50 As accumulates. This material is regarded as translationally
inactive. From 18 h on, further poly(A) shortening and degradation of the
transcript occurs. Again, 20 E has an accelerating effect. In accordance with the
results of the run-on experiments, there is a second increase in GmPCP52 mRNA
with poly(A) tail lengths greater than 50 A. Epofenonane causes delay but does
not prevent the changes observed in untreated animals. The results demonstrate,
that expression of the GmPCP52 gene is regulated at the level of transcription,
translation, as well as transcript accumulation and degradation. Targets of
hormonal action are discussed.
PMID- 9634487
TI - Drosophila OVO zinc-finger protein regulates ovo and ovarian tumor target
promoters.
AB - The ovo+ and ovarian tumor+ genes function in the germline sex determination
pathway in Drosophila, but the hierarchical relationship between them is unknown.
We found that increased ovo+ copy number resulted in increased ovarian tumor
expression in the female germline and increased ovo expression in the male
germline. The ovo locus encodes C2H2 zinc-finger proteins. Bacterially expressed
OVO zinc-finger domain bound to multiple sites at or near the ovo and ovarian
tumor promoters strongly suggesting that OVO is directly autoregulatory and that
ovarian tumor is a direct downstream target of ovo in the germline sex
determination hierarchy. Both positive and negative regulation by OVO proteins
appears likely, depending on promoter context and on the sex of the fly. Our
observation that two strong OVO-binding sites are at the initiator of the TATA
less ovo-B and ovarian tumor promoters raises the possibility that OVO proteins
influence the nucleation of transcriptional pre-initiation complexes.
PMID- 9634488
TI - Otx cognates in a lamprey, Lampetra japonica.
AB - Gnathostomes have two lineages of Otx genes, Otx1 and Otx2, as cognates of a
Drosophila head gap gene, orthodenticle. Previous studies with mutant mice have
demonstrated that they play essential roles in the development of rostral head.
To shed lights on the evolution of the rostral head in vertebrates we isolated
their cognates in the Japanese marine lamprey, Lampetra japonica. The lamprey
genome appeared to have two Otx cognantes, LjOtxA and LjOtxB. Phylogenetic
analyses suggest that LjOtxA clusters with gnathostome Otx2 genes, but LjOtxB
does not belong to either the Otx1 or Otx2 lineage. LjOtxA was expressed in the
forebrain and midbrain with the caudal limit possibly at the midbrain/hindbrain
junction as gnathostome Otx cognates are, but LjOtxB was not expressed in the
brain. No Otx1 or Otx2 cognates are known in gnathostomes that are not expressed
in the brain. Both LjOtxA and LjOtxB were expressed in the olfactory placode,
epiphysis, optic stalks, and lower and upper lips. LjOtxB was also expressed in
the eyes, where no LjOtxA transcripts were detected. Thus, Otx1 and Otx2
functions for the development of forebrain and midbrain in gnathostomes appear to
be shouldered by LjOtxA alone in the lamprey. LjOtxB may have diverged from the
stem of the Otx1 and Otx2 lineages and evolved independently.
PMID- 9634490
TI - Introduction.
AB - Copyright
PMID- 9634489
TI - Myosin and actin are necessary for polar lobe formation and resorption in
Ilyanassa obsoleta embryos.
AB - During the first mitotic divisions many spiralian embryos form a cytoplasmic
protrusion at the vegetal pole called the polar lobe. In the gastropod Ilyanassa
obsoleta the polar lobe is constricted by a contractile ring composed of
filamentous actin, myosin, and associated proteins, similar to the contractile
ring of the cleavage furrow. To resolve the role of myosin and actin in polar
lobe formation and resorption, we have applied 2,3-butanedione monoxime and
Latrunculin B at different stages of the first cleavage to inhibit myosin and F
actin, respectively. Our results show that myosin is important for both
cytokinesis and polar lobe formation. Additionally, we have found that the
resorption of the polar lobe is a two-step process: the first step is passive,
driven by the tension of the actin-cortex and the second step is active, in which
the ATP-hydrolysis of myosin/actin interaction supplies the force to complete the
resorption of the polar lobe. We have summarized our results in a scheme of the
first cleavage of Ilyanassa obsoleta.
PMID- 9634491
TI - Concepts of oxygen transport at the microcirculatory level.
AB - This article compares and contrasts the classic paradigms underlying the
development of chronic and acute hypoxia in tumors. The classic theory of
Thomlinson and Gray suggested that chronic hypoxia is the result of large
intravascular distances. Newer evidence suggests that a multiplicity of effects
contribute to this process, including steep longitudinal gradients of partial
pressure of oxygen (Po2) along the vascular tree before arteriolar entry into
tumor, rheologic effects on red cell deformability brought on by intravascular
hypoxia, uneven distribution of red cell fluxes in microvessels leading to plasma
channels, irregular vascular geometry, and oxygen demand that is out of balance
with the supply. The most common theories have suggested that vascular stasis is
the most common source of acute hypoxia. If this were true, the incidence of this
form of hypoxia would be relatively rare because most studies indicate that total
stasis probably occurs less than 5% of the time. Studies have suggested, however,
that spontaneous fluctuation in tumor blood flow, on the microregional level, can
lead to tissue hypoxia, and total vascular stasis is not required. Spontaneous
fluctuations in flow and Po2 appear to occur commonly. Thus, the most current
evidence suggests that tumor oxygenation is in a continuous state of flux.
Collectively, this new information has important implications for therapy
resistance and gene expression.
PMID- 9634492
TI - Modification of tumor blood flow: current status and future directions.
AB - Suboptimal drug distribution and hypoxia, which can contribute to treatment
failure, are a direct consequence of the spatial and temporal heterogeneity in
perfusion that occurs in solid tumors. Therefore, improvements in tumor blood
flow have wide-ranging therapeutic importance. Paradoxically, controlled
decreases in tumor blood flow can also be exploited and, if permanent, induce
extensive tumor cell death on their own. We review the current knowledge of the
factors controlling tumor blood flow with emphasis on the roles of the
endogeneous vasodilator nitric oxide and the endogenous vasoconstrictor
endothelin-1. The potential importance and application of approaches that
irreversibly damage vascular function, so-called vascular targeting, are also
discussed. Emphasis is given to the drug-based approaches to vascular targeting
that are now entering clinical evaluation. There is no doubt that increased
understanding of the processes that determine blood flow in tumors, coupled with
the availability of techniques to monitor blood flow noninvasively in the clinic,
will enable strategies for selectively modifying tumor blood flow to be
transferred from the laboratory to the clinical setting.
PMID- 9634493
TI - Transvascular drug delivery in solid tumors.
AB - The microvessel wall is a barrier for the delivery of various therapeutic agents
to tumor cells. Tumor microvessels are, in general, more permeable to
macromolecules than normal vessels. The hyperpermeability is presumably due to
the existence of large pore structures in the vessel wall, induced by various
cytokines. The cutoff pore size is tumor dependent, as determined by transport
studies of nanoparticles. The vascular permeability is heterogeneous in tumors
and dependent on physicochemical properties of molecules as well as the
ultrastructure of the vessel wall. The ultrastructure is dynamic and can be
modulated by the tumor microenvironment. The microenvironment itself can be
altered by the transvascular transport because the transport may facilitate
angiogenesis, reduce blood flow, and induce interstitial hypertension in tumors.
Future studies of transport need to address mechanisms of the barrier formation
and emphasize development of novel strategies for circumventing or exploiting the
vascular barrier.
PMID- 9634494
TI - Tumor pH: implications for treatment and novel drug design.
AB - Although limited data exist, electrode-measured pH values of human tumors and
adjacent normal tissues, which are concurrently obtained by the same investigator
in the same patient, consistently show that the electrode pH (believed to
represent tissue extracellular pH primarily) is substantially and consistently
lower in tumor than in normal tissue. In contrast, the 31P-magnetic resonance
spectroscopy-estimated intracellular pH is essentially identical or slightly more
basic in tumor compared with normal tissue. As a consequence, the cellular pH
gradient is substantially reduced or reversed in these tissues. This difference
provides an exploitable avenue for the treatment of cancer. The extent to which
drugs exhibiting weakly acid or basic properties are ionized depends on their
ionization potential (pKa) and the pH of their milieu. Weakly acidic drugs that
are lipid soluble in their nonionized state diffuse freely across the cell
membrane and on entering a relatively basic intracellular compartment become
trapped and accumulate within the cell. This may lead to substantial (10-fold or
more) differences in the intracellular-to-extracellular drug distribution between
tumor and normal tissue for cytotoxics, hypoxic cell sensitizers, or other drugs
exhibiting appropriate pKa. Experimental in vitro evaluation of these predictions
confirms both the predicted pH gradient-dependent changes in cellular drug
accumulation and toxicity.
PMID- 9634495
TI - Evaluating tumor biology and oncological disease with positron-emission
tomography.
AB - The usefulness of positron-emission tomography (PET) for noninvasive assessment
of several biological parameters of neoplastic tissue has been reviewed. Numerous
radiotracers have been developed, whose particular distribution in the presence
of cancer in vivo serves to distinguish medically relevant properties of the
tumor cells with which they associate. That distribution is most accurately
determined through use of a PET scanner, to localize and quantify the tracer
molecules, in which have been incorporated positron-emitting isotopes. These
tracers include hypoxia markers, receptor ligands, substrates for enzymatic
modification by the products of expression of specific genes, and precursors of
protein anabolism and carbohydrate catabolism. In addition, application of PET to
evaluation of patients with some particular cancers has been examined, while
placing special emphasis on the level of scientific rigor of the evidence
underlying conclusions about appropriate use of PET in oncology.
PMID- 9634496
TI - Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation
and blood flow.
AB - The application of functional magnetic resonance (MR) imaging techniques to the
measurement of oxygenation and blood flow in tumors is described. Gradient
recalled echo MR imaging (GRE-MRI) offers a real-time noninvasive method for
monitoring tumor response to vasomodulators such as carbogen (95% O2/5% CO2)
breathing in attempts to overcome tumor hypoxia and improve treatment efficacy.
Although the response is tumor-type dependent, increases in signal intensity of
up to 100% have been observed in several animal tumor types. Responses are also
seen in human tumors. The observed increases in GRE-MRI signal intensity are due
to a combination of a reduction of deoxyhemoglobin in the blood causing changes
in the MR imaging relaxation time T2* and changes in blood flow and may also
reflect the capillary density. Thus, the magnitude of the GRE image intensity
change gives an indication of the potential response of an individual tumor to
treatments that aim to improve tissue oxygenation and therefore how the tumor may
respond to therapy. In addition, carbogen breathing by the host has been shown to
increase the uptake and efficacy of chemotherapeutic agents in animal tumors.
PMID- 9634497
TI - Microenvironmental control of gene expression: implications for tumor
angiogenesis, progression, and metastasis.
AB - Low oxygen tension (hypoxia) is an important prognostic factor in cancer
treatment because it affects tumor formation and malignant progression. Many
genes governing these complex processes have been found to be oxygen regulated.
This article reviews the present knowledge of hypoxia-inducible gene expression
and how this affects angiogenesis, progression, and metastasis. Of particular
importance are hypoxia-regulated transcription factors because they can modulate
expression of countless different genes. Additional genes analyzed in some detail
include those encoding angiogenic growth factors, factors controlling blood flow,
and those involved in metastasis. Although hypoxia is generally perceived as a
hindrance to cancer therapy, it is possibly exploitable because severe oxygen
deficiency is tumor specific. Strategies aimed at using the presence of hypoxia
in solid tumors include oxygen sensitive chemotherapy and gene therapy.
PMID- 9634498
TI - Microdissection, microchip arrays, and molecular analysis of tumor cells (primary
and metastases).
AB - Advances in biotechnology and bioinformatics are offering promise for new
breakthroughs in gene discovery and elucidation of gene function. At present,
many candidate genes related to cancer pathogenesis have been identified in
several types of human cancer, yet frequently their function remains elusive.
This is particularly true as it relates to the progression of human cancer. This
landscape could change dramatically, however, as technological innovations and
improvements continue to revolutionize these fields. High-throughput molecular
approaches are emerging, which may become accurate, automated, and cost
effective. For example, DNA arrays on microchips are under development with
numerous applications, including the ability to screen genes rapidly for
mutations and to study patterns of gene expression on a large scale. Automated
systems for microdissection and sequencing are also in their implementation
stages. Commensurate with their integration and evolution, these information and
technological tools have the potential to offer a more comprehensive
understanding of multiple genetic and cellular alterations occurring during
cancer initiation, development, and progression. Ultimately, this fundamental
knowledge can provide strategies for intervention, prevention, and early
diagnosis. This is a US government work. There are no restrictions on its use.
PMID- 9634499
TI - Radiation dose response for subclinical metastases.
AB - The development of adjuvant therapies for subclinical metastases has been
empiric. Decades of experience showed that 45 to 50 Gy resulted in high control
rates for subclinical lymph node involvement.1 By analogy with the response of
macroscopic tumors, in which doses below a threshold yield no benefit, it was
commonly believed that doses lower than 40 to 50 Gy would not be useful in
elective treatment of subclinical disease. Biological phenomena, such as presumed
metastatic tumor cell burden and growth rate of micrometastases, which could
guide the oncologist, had little or no role in the empirical development of
adjuvant cytotoxic therapies. In this article, some assumptions regarding the
biology of subclinical metastases are discussed and examined in the light of
treatment responses reported from clinical experience. In particular, the
importance of early initiation of adjuvant therapy can be appreciated as well as
the significant reductions in the incidence of metastases that can be achieved
even when doses less than 45 to 50 Gy have to be accepted if necessitated by
normal tissue tolerance.
PMID- 9634500
TI - Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis:
strong disequilibrium effects provide evidence for a major determinant in the HLA
B/-C region.
AB - Although psoriasis is strongly associated with certain human leukocyte antigens
(HLAs), evidence for linkage to HLA markers has been limited. The objectives of
this study were (1) to provide more definitive evidence for linkage of psoriasis
to HLA markers in multiplex families; (2) to compare the major HLA risk alleles
in these families with those determined by previous case-control studies; and (3)
to localize the gene more precisely. By applying the transmission/disequilibrium
test (TDT) and parametric linkage analysis, we found evidence for linkage of
psoriasis to HLA-C, -B, -DR, and -DQ, with HLA-B and -C yielding the most
significant results. Linkage was detectable by parametric methods only when
marker-trait disequilibrium was considered. Case-control association tests and
the TDT identified alleles belonging to the EH57.1 ancestral haplotype as the
major risk alleles in our sample. Among individuals carrying recombinant
ancestral haplotypes involving EH57. 1, the class I markers were retained
selectively among affecteds four times more often than among unaffecteds; among
the few affected individuals carrying only the class II alleles from the
ancestral haplotype, all but one also carried Cw6. These data show that familial
and "sporadic" psoriasis share the same risk alleles. They also illustrate that
substantial parametric linkage information can be extracted by accounting for
linkage disequilibrium. Finally, they strongly suggest that a major
susceptibility gene resides near HLA-C.
PMID- 9634501
TI - Direct evidence for suppression of recombination within two pericentric
inversions in humans: a new sperm-FISH technique.
AB - Crossover within a pericentric inversion produces reciprocal recombinant
chromosomes that are duplicated/deficient for all chromatin distal to the
breakpoints. In view of this fact, a new technique is presented for estimating
the frequency of recombination within pericentric inversions. YAC probes were
selected from within the q- and p-arm flanking regions of two human inversions,
and two-color FISH analysis was performed on sperm from heterozygous inversion
carriers. A total of 6,006 sperm were analyzed for chromosome 1 inversion
(p31q12), and 3,168 were analyzed for chromosome 8 inversion (p23q22). Both
inversions displayed suppression of crossing-over, although the amount of
suppression differed between the two inversions. The recombination frequency of
13.1% recorded for chromosome 8 inversion was similar to the frequency of 11.4%
previously estimated by the human/hamster-fusion method. For chromosome 1
inversion, the recombination frequency of 0. 4% reported here was below the
limits of detection of the fusion technique. The simplicity of the FISH technique
and the ease of scoring facilitate analysis of a sample-population size much
larger than previously had been possible.
PMID- 9634502
TI - Genetic association of apolipoprotein E with age-related macular degeneration.
AB - Age-related macular degeneration (AMD) is the most common geriatric eye disorder
leading to blindness and is characterized by degeneration of the neuroepithelium
in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein
of the CNS and an important regulator of cholesterol and lipid transport, appears
to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a
strong risk factor for various neurodegenerative diseases, and the apoE protein
has been demonstrated in disease-associated lesions of these disorders.
Hypothesizing that variants of APOE act as a potential risk factor for AMD, we
performed a genetic-association study among 88 AMD cases and 901 controls derived
from the population-based Rotterdam Study in the Netherlands. The APOE
polymorphism showed a significant association with the risk for AMD; the APOE
epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95%
confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a
slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2.
82]). To investigate whether apoE is directly involved in the pathogenesis of
AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found
that apoE staining was consistently present in the disease-associated deposits in
AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that
APOE is a susceptibility gene for AMD.
PMID- 9634503
TI - Alternative interpretation of reported paracentric inversion.
PMID- 9634505
TI - PedCheck: a program for identification of genotype incompatibilities in linkage
analysis.
AB - Prior to performance of linkage analysis, elimination of all Mendelian
inconsistencies in the pedigree data is essential. Often, identification of
erroneous genotypes by visual inspection can be very difficult and time
consuming. In fact, sometimes the errors are not recognized until the stage of
running linkage-analysis software. The effort then required to find the erroneous
genotypes and to cross-reference pedigree and marker data that may have been
recoded and renumbered can be not only tedious but also quite daunting, in the
case of very large pedigrees. We have implemented four error-checking algorithms
in a new computer program, PedCheck, which will assist researchers in identifying
all Mendelian inconsistencies in pedigree data and will provide them with useful
and detailed diagnostic information to help resolve the errors. Our program,
which uses many of the algorithms implemented in VITESSE, handles large data sets
quickly and efficiently, accepts a variety of input formats, and offers various
error-checking algorithms that match the subtlety of the pedigree error. These
algorithms range from simple parent-offspring-compatibility checks to a single
locus likelihood-based statistic that identifies and ranks the individuals most
likely to be in error. We use various real data sets to illustrate the power and
effectiveness of our program.
PMID- 9634504
TI - Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in
Ashkenazi Jewish breast cancer patients.
AB - Based on breast cancer families with multiple and/or early-onset cases, estimates
of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may
be as high as 85%. The risk for individuals not selected for family history or
other risk factors is uncertain. We determined the frequency of the common BRCA1
(185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268
anonymous Ashkenazi Jewish women with breast cancer, regardless of family history
or age at onset. DNA was analyzed for the three mutations by allele-specific
oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI]
1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20
2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT
mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the
BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%,
approximately three times the overall risk for the general population (relative
risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number
of carriers found, further studies are necessary. The results differ markedly
from previous estimates based on high-risk breast cancer families and are
consistent with lower estimates derived from a recent population-based study in
the Baltimore area. Thus, presymptomatic screening and counseling for these
common mutations in Ashkenazi Jewish women not selected for family history of
breast cancer should be reconsidered until the risk associated with these
mutations is firmly established, especially since early diagnostic and preventive
treatment modalities are limited.
PMID- 9634506
TI - Localization of a gene (CORD7) for a dominant cone-rod dystrophy to chromosome
6q.
PMID- 9634507
TI - Sequence homology between 4qter and 10qter loci facilitates the instability of
subtelomeric KpnI repeat units implicated in facioscapulohumeral muscular
dystrophy.
AB - Physical mapping and in situ hybridization experiments have shown that a
duplicated locus with a structural organization similar to that of the 4q35 locus
implicated in facioscapulohumeral muscular dystrophy is present in the
subtelomeric portion of 10q. We performed sequence analysis of the p13E-11 probe
and of the adjacent KpnI tandem-repeat unit derived from a 10qter cosmid clone
and compared our results with those published, by other laboratories, for the
4q35 region. We found that the sequence homology range is 98%-100% and confirmed
that the only difference that can be exploited for differentiation of the 10qter
from the 4q35 alleles is the presence of an additional BlnI site within the
10qter KpnI repeat unit. In addition, we observed that the high degree of
sequence homology does facilitate interchromosomal exchanges resulting in
displacement of the whole set of BlnI-resistant or BlnI-sensitive KpnI repeats
from one chromosome to the other. However, partial translocations escape
detection if the latter simply relies on the hybridization pattern from double
digestion with EcoRI/BlnI and with p13E-11 as a probe. We discovered that the
restriction enzyme Tru9I cuts at both ends of the array of KpnI repeats of
different chromosomal origins and allows the use of cloned KpnI sequences as a
probe by eliminating other spurious fragments. This approach coupled with BlnI
digestion permitted us to investigate the structural organization of BlnI
resistant and BlnI-sensitive units within translocated chromosomes of 4q35 and
10q26 origin. A priori, the possibility that partial translocations could play a
role in the molecular mechanism of the disease cannot be excluded.
PMID- 9634508
TI - Evidence that a locus for familial high myopia maps to chromosome 18p.
AB - Myopia, or nearsightedness, is the most common human eye disorder. A genomewide
screen was conducted to map the gene(s) associated with high, early-onset,
autosomal dominant myopia. Eight families that each included two or more
individuals with >=-6.00 diopters (D) myopia, in two or more successive
generations, were identified. Myopic individuals had no clinical evidence of
connective-tissue abnormalities, and the average age at diagnosis of myopia was
6.8 years. The average spherical component refractive error for the affected
individuals was -9.48 D. The families contained 82 individuals; of these, DNA was
available for 71 (37 affected). Markers flanking or intragenic to the genes for
Stickler syndrome types 1 and 2 (chromosomes 12q13.1-q13.3 and 6p21.3,
respectively), Marfan syndrome (chromosome 15q21.1), and juvenile glaucoma
(chromosome 1q21-q31) were also analyzed. No evidence of linkage was found for
markers for the Stickler syndrome types 1 and 2, the Marfan syndrome, or the
juvenile glaucoma loci. After a genomewide search, evidence of significant
linkage was found on chromosome 18p. The maximum LOD score was 9.59, with marker
D18S481, at a recombination fraction of .0010. Haplotype analysis further refined
this myopia locus to a 7.6-cM interval between markers D18S59 and D18S1138 on
18p11.31.
PMID- 9634509
TI - Mapping genes that underlie ethnic differences in disease risk: methods for
detecting linkage in admixed populations, by conditioning on parental admixture.
AB - Genes that underlie ethnic differences in disease risk can be mapped in affected
individuals of mixed descent if the ancestry of the alleles at each marker locus
can be assigned to one of the two founding populations. Linkage can be detected
by testing for association of the disease with the ancestry of alleles at the
marker locus, by conditioning on the admixture (defined as the proportion of
genes that have ancestry from the high-risk population) of both parents. With
regard to exploiting the effects of admixture, this test is more flexible and
powerful than the transmission-disequilibrium test. Under the assumption of a
multiplicative model, the statistical power for a given sample size depends only
on parental admixture and the risk ratio r between populations that is generated
by the locus. The most informative families are those in which mean parental
admixture is .2-.7 and in which admixture is similar in both parents. The number
of markers required for a genome search depends on the number of generations
since admixture and on the information content for ancestry (f) of the markers,
defined as a function of allele frequencies in the two founding populations.
Simulations using a hidden Markov model suggest that, when admixture has occurred
2-10 generations earlier, a multipoint analysis using 2,000 biallelic markers,
with f values of 30%, can extract 70%-90% of the ancestry information for each
locus. Sets of such markers could be selected from libraries of single-nucleotide
polymorphisms, when these become available.
PMID- 9634510
TI - Mapping of complex traits by single-nucleotide polymorphisms.
AB - Molecular geneticists are developing the third-generation human genome map with
single-nucleotide polymorphisms (SNPs), which can be assayed via chip-based
microarrays. One use of these SNP markers is the ability to locate loci that may
be responsible for complex traits, via linkage/linkage-disequilibrium analysis.
In this communication, we describe a semiparametric method for combined
linkage/linkage-disequilibrium analysis using SNP markers. Asymptotic results are
obtained for the estimated parameters, and the finite-sample properties are
evaluated via a simulation study. We also applied this technique to a simulated
genome-scan experiment for mapping a complex trait with two major genes. This
experiment shows that separate linkage and linkage-disequilibrium analyses
correctly detected the signals of both major genes; but the rates of false
positive signals seem high. When linkage and linkage-disequilibrium signals were
combined, the analysis yielded much stronger and clearer signals for the presence
of two major genes than did two separate analyses.
PMID- 9634511
TI - Cytochrome c oxidase deficiency associated with the first stop-codon point
mutation in human mtDNA.
AB - We have identified the first stop-codon point mutation in mtDNA to be reported in
association with human disease. A 36-year-old woman experienced episodes of
encephalopathy accompanied by lactic acidemia and had exercise intolerance and
proximal myopathy. Histochemical analysis showed that 90% of muscle fibers
exhibited decreased or absent cytochrome c oxidase (COX) activity. Biochemical
studies confirmed a severe isolated reduction in COX activity. Muscle
immunocytochemistry revealed a pattern suggestive of a primary mtDNA defect in
the COX-deficient fibers and was consistent with either reduced stability or
impaired assembly of the holoenzyme. Sequence analysis of mtDNA identified a
novel heteroplasmic G-->A point mutation at position 9952 in the patient's
skeletal muscle, which was not detected in her leukocyte mtDNA or in that of 120
healthy controls or 60 additional patients with mitochondrial disease. This point
mutation is located in the 3' end of the gene for subunit III of COX and is
predicted to result in the loss of the last 13 amino acids of the highly
conserved C-terminal region of this subunit. It was not detected in mtDNA
extracted from leukocytes, skeletal muscle, or myoblasts of the patient's mother
or her two sons, indicating that this mutation is not maternally transmitted.
Single-fiber PCR studies provided direct evidence for an association between this
point mutation and COX deficiency and indicated that the proportion of mutant
mtDNA required to induce COX deficiency is lower than that reported for tRNA-gene
point mutations. The findings reported here represent only the second case of
isolated COX deficiency to be defined at the molecular genetic level and reveal a
new mutational mechanism in mitochondrial disease.
PMID- 9634512
TI - Evidence for linkage of human primary systemic carnitine deficiency with D5S436:
a novel gene locus on chromosome 5q.
AB - Primary systemic carnitine deficiency (SCD) is a rare hereditary disorder
transmitted by an autosomal recessive mode of inheritance. The disorder includes
cardiomyopathy, muscle weakness, hypoketotic coma with hypoglycemia, and
hyperammonemia. In this study, we conducted a linkage analysis of a Japanese SCD
family with a proband-a 9-year-old girl-and 26 members. The serum and urinary
carnitine levels were determined for all members. The entire genome was searched
for linkage to the gene locus for SCD, by use of a total of approximately 300
polymorphic markers located approximately 15-20 cM apart. In the family, there
were two significantly different phenotypes, in terms of serum free-carnitine
levels: low serum free-carnitine level (29.5+/-5.0 microM; n=14) and normal serum
free-carnitine level (46.8+/-6.2 microM; n=12). There was no correlation of
urinary free-carnitine levels with the low serum-level phenotype (putative
heterozygote), but in normal phenotypes (wild type) urinary levels decreased as
the serum levels decreased; renal resorption of free carnitine appeared to be
complete in wild-type individuals, when the serum free-carnitine level was <36
microM. Linkage analysis using an autosomal dominant mode of inheritance of
heterozygosity revealed a tight linkage between the disease allele and D5S436 on
chromosome 5q, with a two-point LOD score of 4.98 and a multipoint LOD score of
5.52. The haplotype analysis revealed that the responsible genetic locus lies
between D5S658 and D5S434, which we named the "SCD" locus. This region was
syntenic with the jvs locus, which is responsible for murine SCD. Phylogenic
conversion of the SCD locus strongly suggests involvement of a single gene, in
human SCD.
PMID- 9634513
TI - Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital
hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM
interval on chromosome 1q42-43.
AB - The syndrome of hypoparathyroidism associated with growth retardation,
developmental delay, and dysmorphism (HRD) is a newly described, autosomal
recessive, congenital disorder with severe, often fatal consequences. Since the
syndrome is very rare, with all parents of affected individuals being
consanguineous, it is presumed to be caused by homozygous inheritance of a single
recessive mutation from a common ancestor. To localize the HRD gene, we performed
a genomewide screen using DNA pooling and homozygosity mapping for apparently
unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed
linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination
fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179
in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of
additional chromosome 1 markers revealed evidence of genetic linkage
disequilibrium and place the HRD locus within an approximately 1-cM interval
defined by D1S1540 and D1S2678 on chromosome 1q42-43.
PMID- 9634514
TI - Localization of a gene for molybdenum cofactor deficiency, on the short arm of
chromosome 6, by homozygosity mapping.
AB - Molybdenum cofactor deficiency (MoCoD) is a fatal disorder manifesting, shortly
after birth, with profound neurological abnormalities, mental retardation, and
severe seizures unresponsive to any therapy. The disease is a monogenic,
autosomal recessive disorder, and the existence of at least two complementation
groups suggests genetic heterogeneity. In humans, MoCoD leads to the combined
deficient activities of sulfite oxidase, xanthine dehydrogenase, and aldehyde
oxidase. By using homozygosity mapping and two consanguineous affected kindreds
of Israeli-Arab origin, including five patients, we demonstrated linkage of a
MoCoD gene to an 8-cM region on chromosome 6p21.3, between markers D6S1641 and
D6S1672. Linkage analysis generated the highest combined LOD-score value, 3.6, at
a recombination fraction of 0, with marker D6S1575. These results now can be used
to perform prenatal diagnosis with microsatellite markers. They also provide the
only tool for carrier detection of this fatal disorder.
PMID- 9634515
TI - Acromesomelic dysplasia Maroteaux type maps to human chromosome 9.
AB - Acromesomelic dysplasias are skeletal disorders that disproportionately affect
the middle and distal segments of the appendicular skeleton. We report genetic
mapping studies in four families with acromesomelic dysplasia Maroteaux type
(AMDM), an autosomal recessive osteochondrodysplasia. A peak LOD score of 5.1 at
recombination fraction 0 was obtained with fully informative markers on human
chromosome 9. In three of the four families, the affected offspring are products
of consanguineous marriages; if it is assumed that these affected offspring are
homozygous by descent for the region containing the AMDM locus, a 6.9-cM AMDM
candidate interval can be defined by markers D9S1853 and D9S1874. The mapping of
the AMDM locus to human chromosome 9 indicates that AMDM is genetically distinct
from the two other mapped acromesomelic dysplasias, Hunter-Thompson type and
Grebe type, which are caused by mutations in CDMP1 on human chromosome 20.
PMID- 9634516
TI - Maternal mosaicism for a second mutational event in a type I spinal muscular
atrophy family.
AB - Spinal muscular atrophy (SMA) is a common fatal motor-neuron disorder
characterized by degeneration of the anterior horn cells of the spinal cord,
which results in proximal muscle weakness. Three forms of the disease, exhibiting
differing phenotypic severity, map to chromosome 5q13 in a region of unusually
high genomic variability. The SMA-determining gene (SMN) is deleted or rearranged
in patients with SMA of all levels of severity. A high de novo mutation rate has
been estimated for SMA, based on the deletion of multicopy microsatellite
markers. We present a type I SMA family in which a mutant SMA chromosome has
undergone a second mutation event. Both the occurrence of three affected siblings
harboring this same mutation in one generation of this family and the obligate
carrier status of their mother indicate the existence of maternal germ-line
mosaicism for cells carrying the second mutation. The existence of secondary
mutational events and of germ-line mosaicism has implications for the counseling
of SMA families undergoing prenatal genetic analysis.
PMID- 9634517
TI - Evidence for linkage of spelling disability to chromosome 15.
PMID- 9634518
TI - A European multicenter study of phenylalanine hydroxylase deficiency:
classification of 105 mutations and a general system for genotype-based
prediction of metabolic phenotype.
AB - Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders
caused by mutations in the gene encoding phenylalanine hydroxylase (PAH).
Previous studies have suggested that the highly variable metabolic phenotypes of
PAH deficiency correlate with PAH genotypes. We identified both causative
mutations in 686 patients from seven European centers. On the basis of the
phenotypic characteristics of 297 functionally hemizygous patients, 105 of the
mutations were assigned to one of four arbitrary phenotype categories. We
proposed and tested a simple model for correlation between genotype and
phenotypic outcome. The observed phenotype matched the predicted phenotype in 79%
of the cases, and in only 5 of 184 patients was the observed phenotype more than
one category away from that expected. Among the seven contributing centers, the
proportion of patients for whom the observed phenotype did not match the
predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods
used for mutation detection or phenotype classification may account for a
considerable proportion of genotype-phenotype inconsistencies. Our data indicate
that the PAH-mutation genotype is the main determinant of metabolic phenotype in
most patients with PAH deficiency. In the present study, the classification of
105 PAH mutations may allow the prediction of the biochemical phenotype in
>10,000 genotypes, which may be useful for the management of
hyperphenylalaninemia in newborns.
PMID- 9634519
TI - Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21
22.
AB - Multiple synostoses syndrome is an autosomal dominant disorder characterized by
premature onset of joint fusions, which initially affect the interphalangeal
joints, by characteristic facies, and by deafness. We performed linkage analysis
on a large Hawaiian family with multiple synostoses syndrome. Because another
autosomal dominant disorder, proximal symphalangism, shares some clinical
symptoms with multiple synostoses syndrome and has been linked to markers at loci
at chromosome 17q21-22, we tested the hypothesis that multiple synostoses
syndrome is linked to the same chromosomal region. Using polymorphic markers from
the proximal symphalangism interval, we conducted linkage analysis and showed
that the multiple synostoses-syndrome phenotype is linked to the same chromosomal
region. A maximum LOD score of 3.98 at recombination fraction of .00 was achieved
for the marker at locus D17S787. Further genetic analysis identified individuals
with recombinant genotypes, allowing localization of the disease gene within the
interval D17S931-D17S792, a 16-cM region. These data provide evidence that
multiple synostoses syndrome and proximal symphalangism may be allelic disorders.
PMID- 9634521
TI - Anticipation in familial Hodgkin lymphoma.
PMID- 9634520
TI - The spreading of X inactivation into autosomal material of an x;autosome
translocation: evidence for a difference between autosomal and X-chromosomal DNA.
AB - X inactivation involves initiation, propagation, and maintenance of genetic
inactivation. Studies of replication timing in X;autosome translocations have
suggested that X inactivation may spread into adjacent autosomal DNA. To examine
the inactivation of autosomal material at the molecular level, we assessed the
transcriptional activity of X-linked and autosomal loci spanning an inactive
translocation in a phenotypically normal female with a karyotype of
46,X,der(X)t(X;4)(q22;q24). Since 4q duplications usually manifest dysmorphic
features and severe growth and mental retardation, the normal phenotype of this
individual suggested the spreading of X inactivation throughout the autosomal
material. Consistent with this model, reverse transcription-PCR analysis of 20
transcribed sequences spanning 4q24-qter revealed that three known genes and 11
expressed sequence tags (ESTs) were not expressed in a somatic-cell hybrid that
carries the translocation chromosome. However, three ESTs and three known genes
were expressed from the t(X;4) chromosome and thus "escaped" X inactivation. This
direct assay of expression demonstrated that the spreading of inactivation from
the adjoining X chromosome was incomplete and noncontiguous. These findings are
broadly consistent with the existence of genes known to escape inactivation on
normal inactive X chromosomes. However, the fact that a high proportion (30%) of
tested autosomal genes escaped inactivation may indicate that autosomal material
lacks X chromosome-specific features that are associated with the spreading
and/or maintenance of inactivation.
PMID- 9634522
TI - The 8765delAG mutation in BRCA2 is common among Jews of Yemenite extraction.
PMID- 9634524
TI - Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations
similar to that in hereditary nonpolyposis colorectal cancer families defined by
the Amsterdam criteria.
AB - Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the
coincidence of at least one sebaceous skin tumor and one internal malignancy.
About half of MTS patients are affected by colorectal cancer. In a subgroup of
MTS patients the disease has an underlying DNA mismatch-repair (MMR) defect and
thus is allelic to hereditary nonpolyposis colorectal cancer (HNPCC). The purpose
of this study was to examine to what extent germ-line mutations in DNA MMR genes
are the underlying cause of the MTS phenotype. We ascertained 16 MTS patients
with sebaceous skin tumors and colorectal cancer, and we examined their skin and
visceral tumors for microsatellite instability. All the patients exhibited high
genomic instability in at least one tumor. The search for germ-line mutations in
the hMSH2 and hMLH1 genes in 13 of the MTS patients revealed truncating mutations
in 9 (69%): eight mutations in the hMSH2 gene and one in the hMLH1 gene. This is
the first systematic search for germ-line mutations in patients ascertained on
the basis of sebaceous skin tumors. Our results indicate that (1) MTS patients
exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene;
and (2) the subpopulation of MTS patients who are also affected by colorectal
cancer, irrespective of family history and age at onset of tumors, may have a
likelihood for an underlying DNA MMR defect similar to that for patients with a
family history fulfilling the strict clinical criteria for HNPCC.
PMID- 9634523
TI - A gene for autosomal recessive limb-girdle muscular dystrophy in Manitoba
Hutterites maps to chromosome region 9q31-q33: evidence for another limb-girdle
muscular dystrophy locus.
AB - Characterized by proximal muscle weakness and wasting, limb-girdle muscular
dystrophies (LGMDs) are a heterogeneous group of clinical disorders. Previous
reports have documented either autosomal dominant or autosomal recessive modes of
inheritance, with genetic linkage studies providing evidence for the existence of
at least 12 distinct loci. Gene products have been identified for five genes
responsible for autosomal recessive forms of the disorder. We performed a genome
scan using pooled DNA from a large Hutterite kindred in which the affected
members display a mild form of autosomal recessive LGMD. A total of 200 markers
were used to screen pools of DNA from patients and their siblings. Linkage
between the LGMD locus and D9S302 (maximum LOD score 5.99 at recombination
fraction .03) was established. Since this marker resides within the chromosomal
region known to harbor the gene causing Fukuyama congenital muscular dystrophy
(FCMD), we expanded our investigations, to include additional markers in
chromosome region 9q31-q34.1. Haplotype analysis revealed five recombinations
that place the LGMD locus distal to the FCMD locus. The LGMD locus maps close to
D9S934 (maximum multipoint LOD score 7.61) in a region that is estimated to be
approximately 4.4 Mb (Genetic Location Database composite map). On the basis of
an inferred ancestral recombination, the gene may lie in a 300-kb region between
D9S302 and D9S934. Our results provide compelling evidence that yet another gene
is involved in LGMD; we suggest that it be named "LGMD2H."
PMID- 9634525
TI - Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a
common founder haplotype.
AB - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder
characterized by microcephaly, a birdlike face, growth retardation,
immunodeficiency, lack of secondary sex characteristics in females, and increased
incidence of lymphoid cancers. NBS cells display a phenotype similar to that of
cells from ataxia-telangiectasia patients, including chromosomal instability,
radiation sensitivity, and aberrant cell-cycle-checkpoint control following
exposure to ionizing radiation. A recent study reported genetic linkage of NBS to
human chromosome 8q21, with strong linkage disequilibrium detected at marker
D8S1811 in eastern European NBS families. We collected a geographically diverse
group of NBS families and tested them for linkage, using an expanded panel of
markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of
these families, with a maximum LOD score of 3.58. Significant linkage
disequilibrium was detected for 8/13 markers tested in the 8q21 region, including
D8S1811. In order to further localize the gene for NBS, we generated a radiation
hybrid map of markers at 8q21 and constructed haplotypes based on this map.
Examination of disease haplotypes segregating in 11 NBS pedigrees revealed
recombination events that place the NBS gene between D8S1757 and D8S270. A common
founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS
families. Inferred (ancestral) recombination events involving this common
haplotype suggest that NBS can be localized further, to an interval flanked by
markers D8S273 and D8S88.
PMID- 9634526
TI - Inflation of sibling recurrence-risk ratio, due to ascertainment bias and/or
overreporting.
AB - One widely used measure of familial aggregation is the sibling recurrence-risk
ratio, which is defined as the ratio of risk of disease manifestation, given that
one's sibling is affected, as compared with the disease prevalence in the general
population. Known as lambdaS, it has been used extensively in the mapping of
complex diseases. In this paper, I show that, for a fictitious disease that is
strictly nongenetic and nonenvironmental, lambdaS can be dramatically inflated
because of misunderstanding of the original definition of lambdaS, ascertainment
bias, and overreporting. Therefore, for a disease of entirely environmental
origin, the lambdaS inflation due to ascertainment bias and/or overreporting is
expected to be more prominent if the risk factor also is familially aggregated.
This suggests that, like segregation analysis, the estimation of lambdaS also is
prone to ascertainment bias and should be performed with great care. This is
particularly important if one uses lambdaS for exclusion mapping, for
discrimination between different genetic models, and for association studies,
since these practices hinge tightly on an accurate estimation of lambdaS.
PMID- 9634527
TI - Linkage and association between inflammatory bowel disease and a locus on
chromosome 12.
AB - Genetic epidemiological studies have shown that genetic factors are important in
the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn
disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom
found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We
aimed to replicate this linkage and to narrow the region of interest.
Nonparametric linkage analyses at microsatellites surrounding D12S83 were
performed in 122 North American Caucasian families containing 208 genotyped IBD
affected relative pairs. Transmission/disequilibrium tests (TDTs) were also
performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS
LOD* score 2.76 [P = .00016] between D12S1724 and D12S90). The evidence for
linkage is contributed by both the group of CD-affected relative pairs (peak
GENEHUNTER-PLUS LOD* score 1.79 [P = .0021] between D12S1724 and D12S90) and the
group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [P =
.0019] at D12S335). The TDT is positive at the D12S83 locus (global chi2 = 16.41,
6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to
the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests
that we have greatly narrowed the chromosome 12 region that contains an IBD
locus.
PMID- 9634528
TI - A new locus for autosomal recessive hereditary spastic paraplegia maps to
chromosome 16q24.3.
AB - Hereditary spastic paraplegia is a genetically and phenotypically heterogeneous
disorder. Both pure and complicated forms have been described, with autosomal
dominant, autosomal recessive, and X-linked inheritance. Various loci (SPG1-SPG6)
associated with this disorder have been mapped. Here, we report linkage analysis
of a large consanguineous family affected with autosomal recessive spastic
paraplegia with age at onset of 25-42 years. Linkage analysis of this family
excluded all previously described spastic paraplegia loci. A genomewide linkage
analysis showed evidence of linkage to chromosome 16q24.3, with markers D16S413
(maximum LOD score 3.37 at recombination fraction [theta] of .00) and D16S303
(maximum LOD score 3.74 at straight theta=.00). Multipoint analysis localized the
disease gene in the most telomeric region, with a LOD score of 4.2. These data
indicate the presence of a new locus linked to pure recessive spastic paraplegia,
on chromosome 16q24.3, within a candidate region of 6 cM.
PMID- 9634529
TI - The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T
transversion in NPC1.
AB - Niemann-Pick type D (NPD) disease is a progressive neurodegenerative disorder
characterized by the accumulation of tissue cholesterol and sphingomyelin. This
disorder is relatively common in southwestern Nova Scotia, because of a founder
effect. Our previous studies, using classic linkage analysis of this large
extended kindred, defined the critical gene region to a 13-cM chromosome segment
between D18S40 and D18S66. A recently isolated gene from this region, NPC1, is
mutated in the majority of patients with Niemann-Pick type C disease. We have
identified a point mutation within this gene (G3097-->T; Gly992-->Trp) that shows
complete linkage disequilibrium with NPD, confirming that NPD is an allelic
variant of NPC1.
PMID- 9634530
TI - Pelizaeus-Merzbacher disease: identification of Xq22 proteolipid-protein
duplications and characterization of breakpoints by interphase FISH.
AB - Pelizaeus-Merzbacher disease (PMD) is an X-linked, dysmyelinating disorder of the
CNS. Duplications of the proteolipid protein (PLP) gene have been found in a
proportion of patients, suggesting that, in addition to coding-region or splice
site mutations, overdosage of the gene can cause PMD. We show that the
duplication can be detected by interphase FISH, using a PLP probe in five
patients and their four asymptomatic carrier mothers. The extent of the
duplication was analyzed in each family by interphase FISH, with probes from a 1.
7-Mb region surrounding the PLP gene between markers DXS83 and DXS94. A large
duplication >=500 kb was detected, with breakpoints that differed, between
families, at the proximal end. Distinct separation of the duplicated PLP signals
could be seen only on metaphase chromosomes in one family, providing further
evidence that different duplication events are involved. Quantitative fluorescent
multiplex PCR was used to confirm the duplication in patients, by the detection
of increased copy number of the PLP gene. Multiallelic markers from the
duplicated region were analyzed, since the identification of two alleles in an
affected boy would indicate a duplication. The majority of boys were homozygous
for all four markers, compared with their mothers, who were heterozygous for one
to three of the markers. These results suggest that intrachromosomal
rearrangements may be a common mechanism by which duplications arise in PMD. One
boy was heterozygous for the PLP marker, indicating a duplication and suggesting
that interchromosomal rearrangements of maternal origin also can be involved.
Since duplications are a major cause of PMD, we propose that interphase FISH is a
reliable method for diagnosis and identification of female carriers.
PMID- 9634531
TI - Chromosome 6-linked autosomal recessive early-onset Parkinsonism: linkage in
European and Algerian families, extension of the clinical spectrum, and evidence
of a small homozygous deletion in one family. The French Parkinson's Disease
Genetics Study Group, and the European Consortium on Genetic Susceptibility in
Parkinson's Disease.
AB - The gene for autosomal recessive juvenile Parkinsonism (AR-JP) recently has been
mapped to chromosome 6q25.2-27 in Japanese families. We have tested one Algerian
and 10 European multiplex families with early-onset Parkinson disease for linkage
to this locus, with marker D6S305. Homogeneity analysis provided a conditional
probability in favor of linkage of >.9 in eight families, which were analyzed
further with eight microsatellite markers spanning the 17-cM AR-JP region.
Haplotype reconstruction for eight families and determination of the smallest
region of homozygosity in two consanguineous families reduced the candidate
interval to 11.3 cM. If the deletion of two microsatellite markers (D6S411 and
D6S1550) that colocalize on the genetic map and that segregate with the disease
in the Algerian family is taken into account, the candidate region would be
reduced to <1 cM. These findings should facilitate identification of the
corresponding gene. We have confirmed linkage of AR-JP, in European families and
in an Algerian family, to the PARK2 locus. PARK2 appears to be an important locus
for AR-JP in European patients. The clinical spectrum of the disease in our
families, with age at onset <=58 years and the presence of painful dystonia in
some patients, is broader than that reported previously.
PMID- 9634532
TI - Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome:
implications for imprint-switch models, genetic counseling, and prenatal
diagnosis.
AB - The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the
loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of
patients, this loss of function is due to an imprinting defect. In some cases,
the imprinting defect is the result of a parental imprint-switch failure caused
by a microdeletion of the imprinting center (IC). Here we describe the molecular
analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but
no IC deletion. Heteroduplex and partial sequence analysis did not reveal any
point mutations of the known IC elements, either. Interestingly, all of these
patients represent sporadic cases, and some share the paternal (PWS) or the
maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS
patients informative for the grandparental origin of the incorrectly imprinted
chromosome region and four cases described elsewhere, the maternally imprinted
paternal chromosome region was inherited from the paternal grandmother. This
suggests that the grandmaternal imprint was not erased in the father's germ line.
In seven informative AS patients reported here and in three previously reported
patients, the paternally imprinted maternal chromosome region was inherited from
either the maternal grandfather or the maternal grandmother. The latter finding
is not compatible with an imprint-switch failure, but it suggests that a paternal
imprint developed either in the maternal germ line or postzygotically. We
conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of
a spontaneous prezygotic or postzygotic error, (2) that these cases have a low
recurrence risk, and (3) that the paternal imprint may be the default imprint.
PMID- 9634533
TI - Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli
Opitz syndrome.
AB - The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400])
is an autosomal recessive multiple malformation syndrome due to a defect in
cholesterol biosynthesis. Children with SLOS have elevated serum 7
dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol
levels. On the basis of this biochemical abnormality, it has been proposed that
mutations in the human sterol Delta7-reductase (7-DHC reductase; E.C.1.3.1.21)
gene cause SLOS. However, one could also propose a defect in a gene that encodes
a protein necessary for either the expression or normal function of sterol Delta7
reductase. We cloned cDNA encoding a human sterol Delta7-reductase (DHCR7) on the
basis of its homology with the sterol Delta7-reductase from Arabidopsis thaliana,
and we confirmed the enzymatic function of the human gene product by expression
in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol Delta7
reductase cDNA showed a significant reduction in 7-DHC levels, compared with
those in SLOS fibroblasts transfected with the vector alone. Using radiation
hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To
establish that defects in this gene cause SLOS, we sequenced cDNA clones from
SLOS patients. In three unrelated patients we have identified four different
mutant alleles. Our results demonstrate both that the cDNA that we have
identified encodes the human sterol Delta7-reductase and that mutations in DHCR7
are responsible for at least some cases of SLOS.
PMID- 9634534
TI - Autosomal recessive juvenile parkinsonism maps to 6q25.2-q27 in four ethnic
groups: detailed genetic mapping of the linked region.
AB - Parkinson disease (PD) is a common neurodegenerative condition associated with
degeneration of dopaminergic neurons in the zona compacta of the substantia
nigra. There is increasing evidence that genetic factors play a role in the
etiology of PD, although genetic heterogeneity is likely. An autosomal dominant
syndrome with many similarities to sporadic PD has been mapped to 4q21-22 in a
large Italian pedigree and has been found to be due to mutation of the alpha
synuclein gene. However, this gene appears to account for only a minority of PD,
and a susceptibility locus for autosomal dominant parkinsonism has recently been
mapped, on 2p13. Autosomal recessive juvenile parkinsonism (JP), which shows
marked clinical similarity to PD, maps to 6q25.2-q27. We found linkage to this
region in a group of 15 families from four distinct ethnic backgrounds. A full
genomic screen excluded other candidate regions. We have constructed a detailed
genetic map of the linked region and have mapped the position of the manganese
superoxide dismutase gene (SOD2). Recombination events restricted the JP locus to
a 6.9-cM region and excluded SOD2. The apparent homozygosity for null alleles at
D6S955 in one family suggested a deletion and finer localization of the JP locus.
PMID- 9634535
TI - Host susceptibility to cancer progression.
PMID- 9634536
TI - X-chromosome inactivation spreads itself: effects in autosomes.
PMID- 9634537
TI - Pharmacogenetics of cancer therapy: getting personal.
PMID- 9634538
TI - Nm23-H1: genetic alterations and expression patterns in tumor metastasis.
PMID- 9634539
TI - CD44 isoform-cytoskeleton interaction in oncogenic signaling and tumor
progression.
AB - CD44, a major hyaluronan receptor, exists as several isoforms and is widely
distributed in different cells and tissues. The isoforms of CD44, such as CD44s
(the standard form), CD44E (the epithelial form) and CD44v (variant isoforms)
(arise from differential splicing of one to ten (or eleven) variable exons that
encode portions of the membrane proximal extracellular domain. The molecular
diversity of CD44 isoforms is further compounded by differential biosynthetic
processes and post-translational modifications [e.g. N-/O-glycosylation or
glycosaminoglycan (GAG) addition]. This structural arrangement, which occurs
within either the invariant region or the extracellular domain of the variant
region, is important for CD44-mediated communication between extracellular matrix
materials [ECM-hyaluronic acid (HA), collagen and fibronectin] and intracellular
protein components (e.g cytoskeletal proteins and various regulatory enzymes).
The 15 amino acid sequence [e.g. NSGNGAVEDRKPSGL (in human) or NGGNGTVEDRKPSEL
(in mouse)] residing in the cytoplasmic domain of CD44 isoforms is the ankyrin
binding domain of this family of transmembrane glycoproteins. Biochemical
analyses plus in vitro mutagenesis indicate that the ankyrin-binding domain is
required for CD44-mediated "outside-in" and "inside-out" cell activation events.
Furthermore, CD44s-cytoskeleton interaction is tightly coupled with signal
transducing molecules (e.g. p185HER2 or Src kinases) during oncogenic signaling.
Moreover, the transmembrane linkage between CD44v isoforms (CD44v10 and CD44v3)
and the cytoskeleton up-regulates invasive and metastatic-specific tumor
phenotypes [e.g. matrix degradation (MMPs) activities, tumor cell invasion and
migration]. These findings strongly suggest that the interaction between CD44
isoforms and the cytoskeleton plays a pivotal role in the onset of oncogenesis
and tumor progression.
PMID- 9634540
TI - Plasticity of CD44s expression during progression and metastasis of fibrosarcoma
in an animal model system.
AB - CD44s (standard isoform), which binds hyaluronan (HA), has been analyzed for its
significance during fibrosarcoma progression and metastasis in an athymic nude
mouse model using Balb/c 3T3 cells transformed with ras or sis oncogenes. While
ras (but not sis) transformation leads to upregulated expression of mouse CD44s
and HA binding, transfection/overexpression of human CD44s gene (hCD44s) elicited
remarkable plasticity of expression during progression and metastasis. In 3T3,
hCD44s induced tumorigenesis, HA binding, and micrometastatic competence to lungs
and other organs. In tumorigenic (but nonmetastatic) sis transformants or ras
deleted revertants, it also induced micrometastatic competence. Conversely, large
primary tumors and overt metastases lost hCD44s expression and HA binding via
hypermethylation of hCD44s gene. Tail vein injections revealed that hCD44s
greatly increased the efficiency of colonization of the lung microvasculature at
the earliest stages. These studies indicate that hCD44s overexpression and
possibly its HA binding are critical for conveying metastatic competence but are
antagonistic or selected against during aggressive primary tumor or overt
metastasis outgrowth. This remarkable plasticity of expression and its
consequences offer an ideal system for dissecting the molecular mechanisms
operating during fibrosarcoma progression and metastasis.
PMID- 9634541
TI - Clinical implications of anomalous CD44 gene expression in neoplasia.
AB - An intensive search continues for reliable markers that would be clinically
useful in the diagnosis of small tumors and in the evaluation of their predicted
clinical outcome. One potential marker, extensively studied in human samples is
the cell surface adhesion molecule CD44. The single CD44 gene codes for a large
family of cell surface proteins by alternative splicing and severe abnormalities
have been observed in the patterns of its expression in many types of human
tumors using both protein and RNA-based analyses. These abnormalities are
manifested by markedly increased levels of unusual transcripts and proteins in
tumor cells compared to the corresponding normal tissues. Aberrant processing of
immature CD44 transcripts has also been observed in tumor cells and this can lead
to the inappropriate retention of introns and to the use of cryptic splice sites
in the mRNA. Inappropriate expression patterns of the alternatively spliced exons
have also been linked both to tumor progression and to metastatic potential. The
clinical relevance of all these observations is demonstrated by the frequent
detection of these abnormalities in samples from malignant tumors of many
different organs and by their presence in pre-invasive and high risk pre
cancerous lesions. This article reviews the current information regarding the
expression of the CD44 gene in tumor cells and its potential use as a marker in
clinical evaluation. The overall conclusion is that with the use of the latest
assay techniques and perhaps in combination with other molecular markers,
analysis of CD44 expression can provide new and powerful assays for the detection
of neoplastic disease.
PMID- 9634542
TI - CD44 expression and growth factors.
AB - Soluble factors such as growth factors and cytokines present in the tumor
microenvironment regulate a variety of genes associated with malignant properties
of tumor cells such as growth, migration, invasion, and metastatic capacities.
CD44 is a multi-functional adhesion molecule involved in cell to cell and cell to
extracellular matrix interaction, the trapping of growth factors and cytokines,
and the regulation of cell traffic. Growth factors and cytokines modify the
expression, selective isoform splicing and functions of CD44, resulting in
changes in the biological properties of the cells. These include adhesion of
circulating tumor cells to endothelium and body cavities, and survival in
response to growth factors presented by the CD44 molecule. The modification of
CD44 on both tumor and host cells by growth factors may play an important role in
tumor progression.
PMID- 9634543
TI - The role of CD44 as a cell surface hyaluronan receptor during tumor invasion of
connective tissue.
AB - Tumor progression involves a series of complex interactions between infiltrating
malignant cells and adjacent normal tissues. The cell surface receptor CD44 has
been implicated as an active participant in a number of these interactions.
Although assigned a variety of functions, it is the role of CD44 as a receptor
for the glycosaminoglycan hyaluronan that is likely to be of most importance. The
matrix macromolecule hyaluronan often becomes deposited in the tissue spaces
immediately surrounding invasive tumors. As such, hyaluronan may function as a
ligand for CD44-mediated locomotion or assemble into a protective matrix coat
surrounding the tumor cells. Alternatively, the adjacent hyaluronan-rich matrices
may serve as a barrier to migration, breached in part by aggressive cell types
exhibiting a capacity for CD44-mediated hyaluronan endocytosis. The significance
of tumor-associated hyaluronan accumulation as well as potential functions of
CD44--hyaluronan interactions are reviewed.
PMID- 9634544
TI - CD44 structure and function.
AB - In this review we discuss the structural elements of CD44 that have been shown to
be involved in specific functions. To this end, we focus primarily on experiments
in which CD44 constructs are transfected into cells whose function is then
assayed. The hyaluronan binding function of CD44 has been assayed in cell lines
and in fusion proteins, termed CD44-Igs, consisting of the external domain of
CD44 coupled to the hinge, CH2 and CH3 regions of human IgG1. These studies have
shown that hyaluronan binding by CD44 is regulated by the cells in which it is
expressed, and that at least part of this regulation is determined by cell
specific posttranslational modifications, especially N-glycosylation, of CD44
itself. Variant isoforms of CD44 determined by alternative splicing of 11
optional exons in the middle of the gene determine additional functions of CD44,
as well as contributing to the regulation of hyaluronan binding. Soluble CD44 may
modulate the function of cell surface CD44. The cytoplasmic domain of CD44
contributes to ligand binding in a way that remains obscure. It also determines
membrane localization in polarized epithelial cells, and is probably involved in
CD44 interactions with the cytoskeleton and in mediating post-ligand binding
events.
PMID- 9634546
TI - Role of CD44 in CTL and NK cell activity.
AB - CD44 is a widely distributed cell surface glycoprotein whose principal ligand has
been identified as hyaluronic acid (HA), a major component of the extracellular
matrix (ECM). Recent studies have demonstrated that activation through CD44 leads
to induction of effector function in T cells and macrophages. At sites of chronic
inflammation as seen in certain infections, autoimmune diseases, allograft
rejection, graft-versus-host (GVH) disease and treatment of cancer patients with
high doses of interleukin-2, significant damage to the endothelial cells has been
known to occur, which leads to the toxicity or pathogenesis associated with the
disease. The exact mechanism of endothelial cell damage is not clear, although,
it has been widely speculated that immune cells may play a critical role. Studies
from our laboratory have used interleukin-2 (IL-2) induced vascular leak syndrome
(VLS) as a model to investigate the role of cytolytic lymphocytes in the direct
cytotoxicity of endothelial cells. Cytotoxic T lymphocytes (CTL), double-negative
(DN) T cells and natural killer (NK) cells upon activation express high levels of
CD44 and mediate efficient MHC-unrestricted TCR-independent lysis following
ligation of CD44. Such CD44-mediated cytotoxicity may play an important role in
protection against viral infections and cancer. However, it could also cause non
specific tissue injury. For example, dysregulation in the interaction between
activated cytotoxic lymphocytes expressing CD44 and endothelial cells bearing the
appropriated ligand such as the hyaluronate (HA), could lead to endothelial cell
lysis. Furthermore, such endothelial cell injury could lead to the pathogenesis
associated with a variety of clinical diseases.
PMID- 9634547
TI - Identification of the amino terminus of neuronal Ca2+ channel alpha1 subunits
alpha1B and alpha1E as an essential determinant of G-protein modulation.
AB - We have examined the basis for G-protein modulation of the neuronal voltage
dependent calcium channels (VDCCs) alpha1E and alpha1B. A novel PCR product of
alpha1E was isolated from rat brain. This contained an extended 5' DNA sequence
and was subcloned onto the previously cloned isoform rbEII, giving rise to
alpha1Elong whose N terminus was extended by 50 amino acids. VDCC alpha1 subunit
constructs were co-expressed with the accessory alpha2-delta and beta2a subunits
in Xenopus oocytes and mammalian (COS-7) cells. The alpha1Elong showed
biophysical properties similar to those of rbEII; however, when G-protein
modulation of expressed alpha1 subunits was induced by activation of co-expressed
dopamine (D2) receptors with quinpirole (100 nM) in oocytes, or by co
transfection of Gbeta1gamma2 subunits in COS-7 cells, alpha1Elong, unlike
alpha1E(rbEII), was found to be G-protein-modulated, in terms of both a slowing
of activation kinetics and a reduction in current amplitude. However, alpha1Elong
showed less modulation than alpha1B, and substitution of the alpha1E1-50 with the
corresponding region of alpha1B1-55 produced a chimera alpha1bEEEE, with G
protein modulation intermediate between alpha1Elong and alpha1B. Furthermore,
deletion of the N-terminal 1-55 sequence from alpha1B produced alpha1BDeltaN1-55,
which could not be modulated, thus identifying the N-terminal domain as essential
for G-protein modulation. Taken together with previous studies, these results
indicate that the intracellular N terminus of alpha1E1-50 and alpha1B1-55 is
likely to contribute to a multicomponent site, together with the intracellular I
II loop and/or the C-terminal tail, which are involved in Gbetagamma binding
and/or in subsequent modulation of channel gating.
PMID- 9634548
TI - Age-related changes in neuronal nicotinic acetylcholine receptor subunit alpha4
expression are modified by long-term nicotine administration.
AB - The distribution of the neuronal nicotinic acetylcholine receptor subunit alpha4
(nAChRalpha4) in the brains of young (2-4 months) or aged (24-28 months) CBA/J
mice was examined using immunohistochemical staining. Anti-nAChRalpha4
immunoreactivity corresponded with nAChRalpha4 RNA expression and high-affinity
[3H]nicotine binding. Immunostaining in aged mice relative to that in young
animals was diminished in the medial septum and diagonal band but was unchanged
in the globus pallidus and substantia nigra. The staining of neurons was almost
completely absent in the hippocampus of aged animals. The oral administration of
nicotine to aged animals for 6 weeks did not alter nAChRalpha4 expression
relative to that in aged controls. However, the long-term delivery of nicotine
(11 months) to 14-month-old animals corresponded with the highly specific
preservation of nAChRalpha4 expression in some neurons of the dentate gyrus
region and in neurite processes of remaining neurons of the hippocampal CA1
region. These results support the conclusion that the loss of nAChRalpha4
expression occurs in key cholinergic regions during normal aging. Furthermore,
sustained long-term nicotine delivery may promote highly region-specific
retention of nAChR expression, but only if initiated before normal age-related
receptor decline.
PMID- 9634549
TI - Isoform-specific regulation of the Na+/Ca2+ exchanger in rat astrocytes and
neurons by PKA.
AB - The Na+/Ca2+ exchanger is a major transporter of Ca2+ in neurons and glial cells.
The Na+/Ca2+ exchanger gene NCX1 expresses tissue-specific isoforms of the
Na+/Ca2+ exchanger, and the isoforms have been examined here quantitatively using
primary cultures of astrocytes and neurons. We present a PCR-based quantitative
method, quantitative end-labeled reverse transcription-PCR (QERT-PCR), to
determine the relative amounts of the NCX1 isoforms present in these cells. Six
exons (A, B, C, D, E, and F) are alternatively spliced to produce the known NCX1
isoforms. Three exon B-containing isoforms (BDEF, BDF, and BD) are the
predominant transcripts in primary rat cortical astrocytes and in C6 glioma
cells. In contrast, exon A-containing isoforms (ADF and AD) are the predominant
transcripts in primary rat hippocampal neurons. Functional differences between
full-length constructs of NCX1 containing either the astrocyte isoform BD or the
neuron isoform AD were examined in a Xenopus oocyte expression system. Although
both isoforms function normally, the activity of the AD isoform can be increased
39% by activation of protein kinase A (PKA), whereas that of the BD isoform is
not affected. We conclude that specific NCX1 isoforms are expressed in distinct
patterns in astrocytes and neurons. Furthermore, the activity of a neuronal (but
not glial) isoform of the Na+/Ca2+ exchanger can be altered by the activation of
the PKA pathway.
PMID- 9634550
TI - On the action of the anti-absence drug ethosuximide in the rat and cat thalamus.
AB - The action of ethosuximide (ETX) on Na+, K+, and Ca2+ currents and on tonic and
burst-firing patterns was investigated in rat and cat thalamic neurons in vitro
by using patch and sharp microelectrode recordings. In thalamocortical (TC)
neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75-1 mM)
decreased the noninactivating Na+ current, INaP, by 60% but had no effect on the
transient Na+ current. In TC neurons of the rat and cat LGN, the whole-cell
transient outward current was not affected by ETX (up to 1 mM), but the sustained
outward current was decreased by 39% at 20 mV in the presence of ETX (0.25-0.5
mM): this reduction was not observed in a low Ca2+ (0.5 mM) and high Mg2+ (8 mM)
medium or in the presence of Ni2+ (1 mM) and Cd2+ (100 microM). In addition, ETX
(up to 1 mM) had no effect on the low-threshold Ca2+ current, IT, of TC neurons
of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus
reticularis thalami nor on the high-threshold Ca2+ current in TC neurons of the
rat LGN. Sharp microelectrode recordings in TC neurons of the rat and cat LGN and
VB showed that ETX did not change the resting membrane potential but increased
the apparent input resistance at potentials greater than -60 mV, resulting in an
increase in tonic firing. In contrast, ETX decreased the number of action
potentials in the burst evoked by a low-threshold Ca2+ potential. The frequency
of the remaining action potentials in a burst also was decreased, whereas the
latency of the first action potential was increased. Similar effects were
observed on the burst firing evoked during intrinsic delta oscillations. These
results indicate an action of ETX on INaP and on the Ca2+-activated K+ current,
which explains the decrease in burst firing and the increase in tonic firing,
and, together with the lack of action on low- and high-threshold Ca2+ currents,
the results cast doubts on the hypothesis that a reduction of IT in thalamic
neurons underlies the therapeutic action of this anti-absence medicine.
PMID- 9634551
TI - Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and
uptake: an investigation of extrasynaptic transmission.
AB - Whether neurotransmitters are restricted to the synaptic cleft (participating
only in hard-wired neurotransmission) or diffuse to remote receptor sites
(participating in what has been termed volume or paracrine transmission) depends
on a number of factors. These include (1) the location of release sites with
respect to the receptors, (2) the number of molecules released, (3) the
diffusional rate away from the release site, determined by both the geometry near
the release site as well as binding interactions, and (4) the removal of
transmitter by the relevant transporter. Fast-scan cyclic voltammetry allows for
the detection of extrasynaptic concentrations of many biogenic amines, permitting
direct access to many of these parameters. In this study the hypothesis that 5
hydroxytryptamine (5-HT) transmission is primarily extrasynaptic in the
substantia nigra reticulata, a terminal region with identified synaptic contacts,
and the dorsal raphe nucleus, a somatodendritic region with rare synaptic
incidence, was tested in brain slices prepared from the rat. Using carbon fiber
microelectrodes, we found the concentration of 5-HT released per stimulus pulse
in both regions to be identical when elicited by single pulse stimulations or
trains at high frequency. 5-HT efflux elicited by a single stimulus pulse was
unaffected by uptake inhibition or receptor antagonism. Thus, synaptic efflux is
not restricted by binding to intrasynaptic receptors or transporters. The number
of 5-HT molecules released per terminal was estimated in the substantia nigra
reticulata and was considerably less than the number of 5-HT transporter and
receptor sites, reinforcing the hypothesis that these sites are extrasynaptic.
Furthermore, the detected extrasynaptic concentrations closely match the affinity
for the predominant 5-HT receptor in each region. Although they do not disprove
the existence of classical synaptic transmission, our results support the
existence of paracrine neurotransmission in both serotonergic regions.
PMID- 9634552
TI - Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence
from mice lacking the transporter.
AB - The role of the dopamine transporter (DAT) in mediating the neurotoxic effects of
methamphetamine (METH) was tested in mice lacking DAT. Dopamine (DA) and
serotonin (5-HT) content, glial fibrillary acidic protein (GFAP) expression, and
free radical formation were assessed as markers of METH neurotoxicity in the
striatum and/or hippocampus of wild-type, heterozygote, and homozygote (DAT -/-)
mice. Four injections of METH (15 mg/kg, s.c.), each given 2 hr apart, produced
80 and 30% decreases in striatal DA and 5-HT levels, respectively, in wild-type
animals 2 d after administration. In addition, GFAP mRNA and protein expression
levels, extracellular DA levels, and free radical formation were increased
markedly. Hippocampal 5-HT content was decreased significantly as well (43%).
Conversely, no significant changes were observed in total DA content, GFAP
expression, extracellular DA levels, or free radical formation in the striatum of
DAT -/- mice after METH administration. However, modest decreases were observed
in striatal and hippocampal 5-HT levels (10 and 17%, respectively). These
observations demonstrate that DAT is required for, and DA is an essential
mediator of, METH-induced striatal dopaminergic neurotoxicity, whereas
serotonergic deficits are only partially dependent on DAT.
PMID- 9634553
TI - Evidence for metabotropic glutamate receptor activation in the induction of
depolarization-induced suppression of inhibition in hippocampal CA1.
AB - Depolarization-induced suppression of inhibition (DSI) is a transient reduction
of GABAA receptor-mediated IPSCs that is mediated by a retrograde signal from
principal cells to interneurons. Using whole-cell recordings, we tested the
hypothesis that mGluRs are involved in the DSI process in hippocampal CA1, as has
been proposed for cerebellar DSI. Group II mGluR agonists failed to affect either
evoked monosynaptic IPSCs or DSI, and forskolin, which blocks cerebellar DSI, did
not affect CA1 DSI. Group I and group III mGluR agonists reduced IPSCs, but only
group I agonists occluded DSI. (S)-MCPG blocked (1S,3R)-ACPD-induced IPSC
suppression and markedly reduced DSI, whereas group III antagonists had no effect
on DSI. Many other similarities between DSI and the (1S,3R)-ACPD-induced
suppression of IPSCs also were found. Our data suggest that a glutamate-like
substance released from pyramidal cells could mediate CA1 DSI by reducing GABA
release from interneurons via the activation of group I mGluRs.
PMID- 9634554
TI - Ca2+ channel beta3 subunit enhances voltage-dependent relief of G-protein
inhibition induced by muscarinic receptor activation and Gbetagamma.
AB - The Ca2+ channel beta subunit has been shown to reduce the magnitude of G-protein
inhibition of Ca2+ channels. However, neither the specificity of this action to
different forms of G-protein inhibition nor the mechanism underlying this
reduction in response is known. We have reported previously that coexpression of
the Ca2+ channel beta3 subunit causes M2 muscarinic receptor-mediated inhibition
of alpha1B Ca2+ currents to become more voltage-dependent. We report here that
the beta3 subunit increases the rate of relief of inhibition produced by a
depolarizing prepulse and also shifts the voltage dependency of this relief to
more hyperpolarized voltages; these effects are likely to be responsible for the
reduction of inhibitory response of alpha1B channels to G-protein-mediated
inhibition seen after coexpression of the Ca2+ channel beta3 subunit.
Additionally, the beta3 subunit alters the rate and voltage dependency of relief
of the inhibition produced by coexpressed Gbeta1gamma1, in a manner similar to
the changes it produces in relief of M2 receptor-induced inhibition. We conclude
that the Ca2+ channel beta3 subunit reduces the magnitude of G-protein inhibition
of alpha1B Ca2+ channels by enhancing the rate of dissociation of the G-protein
betagamma subunit from the Ca2+ channel alpha1B subunit.
PMID- 9634555
TI - Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient
forebrain ischemia in the rat.
AB - A short ischemic period induced by the transient occlusion of major brain
arteries induces neuronal damage in selectively vulnerable regions of the
hippocampus. Adenosine is considered to be one of the major neuroprotective
substances produced in the ischemic brain. It can be released from damaged cells,
but it also could be generated extracellularly from released ATP via a surface
located enzyme chain. Using the rat model of global forebrain ischemia, we
applied a short (10 min) transient interruption of blood flow and studied the
distribution of ectonucleotidase activities in the hippocampus. Northern
hybridization of mRNA isolated from hippocampi of sham-operated and ischemic
animals revealed an upregulation of ectoapyrase (capable of hydrolyzing
nucleoside 5'-tri- and diphosphates) and ecto-5'-nucleotidase (capable of
hydrolyzing nucleoside 5'-monophosphates). A histochemical analysis that used
ATP, UTP, ADP, or AMP as substrates revealed a strong and selective increase in
enzyme activity in the injured areas of the hippocampus. Enhanced staining could
be observed first at 2 d. Staining increased within the next days and persisted
at 28 d after ischemia. The spatiotemporal development of catalytic activities
was identical for all substrates. It was most pronounced in the CA1 subfield and
also could be detected in the dentate hilus and to a marginal extent in CA3. The
histochemical staining corresponded closely to the development of markers for
reactive glia, in particular of microglia. The upregulation of ectonucleotidase
activities implies increased nucleotide release from the damaged tissue and could
play a role in the postischemic control of nucleotide-mediated cellular
responses.
PMID- 9634556
TI - rMAL is a glycosphingolipid-associated protein of myelin and apical membranes of
epithelial cells in kidney and stomach.
AB - rMAL, the rat myelin and lymphocyte protein, is a small hydrophobic protein of 17
kDa with four putative transmembrane domains and is expressed in oligodendrocytes
and Schwann cells, the myelinating cells of the nervous system. In addition,
transcript expression has been found in kidney, spleen, and intestine. Confocal
microscopy and immunoelectron microscopy with an affinity-purified antibody
localized rMAL to compact myelin in a pattern similar to the structural myelin
proteins: myelin basic protein and proteolipid protein. In kidney and stomach
epithelia, rMAL is located almost exclusively on the apical (luminal) membranes
of the cells lining distal tubuli in kidney and the glandular part of the
stomach. Biochemical analysis of plasma membranes isolated from spinal cord and
kidney demonstrated that rMAL is a proteolipid that is present in detergent
insoluble complexes typical for proteins associated with glycosphingolipids.
Lipid and protein analysis showed a co-enrichment of glycosphingolipids and rMAL
protein within these complexes, indicating a close association of rMAL to
glycosphingolipids in myelin and in kidney in vivo. We conclude that specific
rMAL-glycosphingolipid interactions may lead to the formation and maintenance of
stable protein-lipid microdomains in myelin and apical epithelial membranes. They
may contribute to specific properties of these highly specialized plasma
membranes.
PMID- 9634557
TI - Induction of caspase-3-like protease may mediate delayed neuronal death in the
hippocampus after transient cerebral ischemia.
AB - Delayed neuronal death after transient cerebral ischemia may be mediated, in
part, by the induction of apoptosis-regulatory gene products. Caspase-3 is a
newly characterized mammalian cysteine protease that promotes cell death during
brain development, in neuronal cultures, and in other cell types under many
different conditions. To determine whether caspase-3 serves to regulate neuronal
death after cerebral ischemia, we have (1) cloned a cDNA encoding the rat brain
caspase-3; (2) examined caspase-3 mRNA and protein expression in the brain using
in situ hybridization, Northern and Western blot analyses, and double-labeled
immunohistochemistry; (3) determined caspase-3-like activity in brain cell
extracts; and (4) studied the effect of caspase-3 inhibition on cell survival and
DNA fragmentation in the hippocampus in a rat model of transient global ischemia.
At 8-72 hr after ischemia, caspase-3 mRNA and protein were induced in the
hippocampus and caudate-putamen (CPu), accompanied by increased caspase-3-like
protease activity. In the hippocampus, caspase-3 mRNA and protein were
predominantly increased in degenerating CA1 pyramidal neurons. Proteolytic
activation of the caspase-3 precursor was detected in hippocampus and CPu but not
in cortex at 4-72 hr after ischemia. Double-label experiments detected DNA
fragmentation in the majority of CA1 neurons and selective CPu neurons that
overexpressed caspase-3. Furthermore, ventricular infusion of Z-DEVD-FMK, a
caspase-3 inhibitor, decreased caspase-3 activity in the hippocampus and
significantly reduced cell death and DNA fragmentation in the CA1 sector up to 7
d after ischemia. These data strongly suggest that caspase-3 activity contributes
to delayed neuronal death after transient ischemia.
PMID- 9634558
TI - Neurturin exerts potent actions on survival and function of midbrain dopaminergic
neurons.
AB - Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on
survival and function of midbrain dopaminergic (DA) neurons in a variety of
models. Although other growth factors expressed in the vicinity of developing DA
neurons have been reported to support survival of DA neurons in vitro, to date
none of these factors duplicate the potent and selective actions of GDNF in vivo.
We report here that neurturin (NTN), a homolog of GDNF, is expressed in the
nigrostriatal system, and that NTN exerts potent effects on survival and function
of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially
expressed in the ventral midbrain and striatum during development and that NTN
exhibits survival-promoting actions on both developing and mature DA neurons. In
vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct
injection of NTN into the substantia nigra protects mature DA neurons from cell
death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of
intact adult animals induces behavioral and biochemical changes associated with
functional upregulation of nigral DA neurons. The similarity in potency and
efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to
the differential distribution of the receptor components GDNF Family Receptor
alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results
suggest that NTN is an endogenous trophic factor for midbrain DA neurons and
point to the possibility that GDNF and NTN may exert redundant trophic influences
on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
PMID- 9634559
TI - Immunohistochemical and cytochemical localization of the somatostatin receptor
subtype sst1 in the somatostatinergic parvocellular neuronal system of the rat
hypothalamus.
AB - Somatostatin is known to mediate its actions through five G-protein-coupled
receptors (sst1-sst5). We have studied the expression of the sst1 receptor in the
rat hypothalamus by using a subtype-specific antiserum. In Western blotting, the
antiserum reacted specifically with a band with an apparent molecular weight of
80,000 in membranes prepared from hypothalamic tissue. The localization of the
sst1 receptor was investigated by immunohistochemistry in hypothalamus sections.
Additionally, an immunofluorescent double-labeling was performed for the sst1
receptor and somatostatin. Light microscopy revealed that the sst1 receptor is
located in perikarya and nerve fibers in the rostral periventricular area
surrounding the third ventricle as well as in nerve fibers projecting from the
perikarya to the external layer of the median eminence. In these neuronal
structures, sst1 immunoreactivity was found to be colocalized with somatostatin.
Furthermore, the location of sst1 receptors was studied by immunoelectron
microscopy in the median eminence. In the external layer, receptor
immunoreactivity was confined to nerve terminals. Immunoreactive nerve terminals
were seen to make synapse-like junctions with other both stained and unstained
nerve terminals. Thus, the sst1 receptor is present in the classic
somatostatinergic hypothalamic parvocellular system inhibiting hormone secretion
from the anterior pituitary gland. These findings indicate that the sst1 receptor
may act as an autoreceptor and inhibit the release of somatostatin from
periventricular neurons projecting to the median eminence.
PMID- 9634560
TI - Acetylcholine triggers L-glutamate exocytosis via nicotinic receptors and
inhibits melatonin synthesis in rat pinealocytes.
AB - Rat pinealocytes, melatonin-secreting endocrine cells, contain peripheral
glutaminergic systems. L-Glutamate is a negative regulator of melatonin synthesis
through a metabotropic receptor-mediated inhibitory cAMP cascade. Previously, we
reported that depolarization of pinealocytes by externally added KCl and
activation of L-type Ca2+ channels resulted in secretion of L-glutamate by
microvesicle exocytosis. What is unknown is how and what kinds of stimuli trigger
glutamate exocytosis under physiological conditions. Here, we report that the
nicotinic acetylcholine receptor can trigger glutamate exocytosis from cultured
rat pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinephrine
dependent serotonin N-acetyltransferase activity, which results in decreased
melatonin synthesis. These activities were blocked by (2S,3S, 4S)-2-methyl-2
(carboxycyclopropyl)glycine, an antagonist of the metabotropic glutamate
receptor. These results suggest that cholinergic stimulation initiates the
glutaminergic signaling cascade in pineal glands and that parasympathetic neurons
innervating the gland exert negative control over melatonin synthesis by way of
the glutaminergic systems.
PMID- 9634561
TI - Axon withdrawal during synapse elimination at the neuromuscular junction is
accompanied by disassembly of the postsynaptic specialization and withdrawal of
Schwann cell processes.
AB - Nerve terminal withdrawal is accompanied by a loss of acetylcholine receptors
(AChRs) at corresponding postsynaptic sites during the process of synapse
elimination at developing () and reinnervated adult () neuromuscular junctions.
Aside from AChR and nerve terminal loss, however, the molecular and cellular
alterations that occur at sites of elimination are unknown. To gain a better
understanding of the cascade of events that leads to the disassembly of synaptic
sites during the synapse elimination process, we surveyed the distribution of
molecular elements of the postsynaptic specialization, the basal lamina, and
supporting Schwann cells during the process of synapse elimination that occurs
after reinnervation. In addition, quantitative techniques were used to determine
the temporal order of disappearance of molecules that were lost relative to the
loss of postsynaptic AChRs. We found that the dismantling of the postsynaptic
specialization was inhomogeneous, with evidence of rapid dissolution of some
aspects of the postsynaptic apparatus and slower loss of others. We also observed
a loss of Schwann cell processes from sites of synapse elimination, with a time
course similar to that seen for nerve terminal retraction. In contrast, all of
the extracellular markers that we examined were lost slowly from sites of synapse
loss. We therefore conclude that the synapse elimination process is synapse-wide,
removing not only nerve terminals but also Schwann cells and many aspects of the
postsynaptic apparatus. The disassembly occurs in a stereotyped sequence with
some synaptic elements appearing much more stable than others.
PMID- 9634562
TI - Activity-dependent development of calcium regulation in growing motor axons.
AB - In cultured nerve cord explants from the crayfish (Procambarus clarkii), the
normal impulse activity levels of growing motor axons determine their response to
Ca2+ influx. During depolarization or Ca2+ ionophore application, normally active
tonic motor axons continue to grow, whereas inactive phasic motor axons retract
and often degenerate. To determine the role of Ca2+ regulation in this
difference, we measured the intracellular free Ca2+ concentration ([Ca2+]i) with
fura-2. Growth cones from tonic axons normally had a higher [Ca2+]i than those
from phasic axons. When depolarized with 60 mM K+, growth cones and neurites from
phasic axons had a [Ca2+]i three to four times higher than did those from tonic
axons. This difference in Ca2+ regulation includes greater Ca2+-handling capacity
for growing tonic axons; the increase in [Ca2+]i produced by the Ca2+ ionophore 4
bromo-A23187 (0.25 microM) is four to five times greater in phasic than in tonic
axons, and the decline in [Ca2+]i at the end of a depolarizing pulse is three to
four times faster in tonic axons than phasic ones. Blocking impulses in growing
tonic axons for 2-3 d with tetrodotoxin reduces their capacity to regulate
[Ca2+]i. Thus, growing tonic and phasic axons have differences in Ca2+ regulation
that develop as a result of their different activity levels. These activity
dependent differences in Ca2+ regulation influence axon growth and degeneration
and probably influence other neuronal processes that are mediated by changes in
[Ca2+]i.
PMID- 9634563
TI - cAMP-mediated regulation of neurotrophin-induced collapse of nerve growth cones.
AB - Neurotrophins are known to promote the survival, differentiation, and neurite
outgrowth of developing neurons. Here we report that acutely applied brain
derived neurotrophic factor (BDNF) induces rapid growth cone collapse and neurite
retraction of embryonic Xenopus spinal neurons in culture. The collapsing effect
of BDNF depends on the activation of Trk receptor tyrosine kinase, requires an
influx of extracellular Ca2+, and is regulated by cAMP-dependent activity.
Elevation of intracellular cAMP levels ([cAMP]i) by forskolin or (Sp)-cAMP
completely blocked the collapsing effect, whereas inhibition of protein kinase A
(PKA) by (Rp)-cAMP potentiated the collapsing action. BDNF-induced growth cone
collapse was only observed in 6 hr cultures but not in 24 hr cultures. However,
inhibition of PKA by (Rp)-cAMP restored the collapsing response of these "old"
neurons in 24 hr cultures, suggesting that embryonic Xenopus spinal neurons may
upregulate their endogenous cAMP-dependent activity during development in
culture, leading to the blockade of their collapsing response to BDNF. Taken
together, our results suggest the presence of cross-talk between Ca2+- and cAMP
signaling pathways involved in the collapsing action of neurotrophins, in which
the cAMP-pathway regulates the Ca2+-mediated signal transduction required for
BDNF-induced collapse. By modulating the cAMP-dependent activity through the
intrinsic programming or interaction with other factors present in the
environment, a neuron thus could respond to the same extracellular factors with
different morphological and cellular changes at different stages during
development.
PMID- 9634564
TI - Localized synaptic actions of neurotrophin-4.
AB - Neurotrophins secreted by the postsynaptic target cell may participate in
activity-dependent synaptic modification during development and in the mature
brain. A fundamental question of how neurotrophins can sculpt synaptic
connections is whether neurotrophin-induced synaptic changes are spatially
restricted to the site of neurotrophin secretion or whether they can spread to
neighboring synapses. Using a model system of nerve-muscle coculture in which
neurotrophin-4 (NT-4) is overexpressed in a subpopulation of postsynaptic
myocytes, we demonstrated that presynaptic potentiation is restricted to synapses
on myocytes overexpressing NT-4 without affecting nearby synapses formed by the
same neuron on control myocytes. Likewise, postsynaptic modulation of
acetylcholine channels by secreted NT-4 is spatially restricted to <60 micron
from the site of NT-4 secretion. Therefore, activity-dependent secretion of
neurotrophins can result in highly localized modification of neuronal
connections.
PMID- 9634565
TI - GABAA receptor pharmacology and subtype mRNA expression in human neuronal NT2-N
cells.
AB - Human NT2 teratocarcinoma cells differentiate into neuron-like NT2-N cells when
treated with retinoic acid. GABA evoked concentration-dependent whole-cell
currents in NT2-N cells with an EC50 of 21.8 microM and a Hill slope of 1.2.
GABAA receptor (GABAR) currents reversed at ECl- and did not display voltage
dependent rectification. GABAR single channels opened in bursts to a 23 pS main
conductance level and a 19 pS subconductance level, with infrequent openings to a
27 pS conductance level. Kinetic properties of the main conductance level were
similar to other native and recombinant GABAR channels. Diazepam and zolpidem
enhanced GABAR currents with moderate affinity, whereas methyl-6, 7-dimethoxy-4
ethyl-beta-carboline-3-carboxylate inhibited GABAR currents. Loreclezole enhanced
GABAR currents with high affinity, but furosemide antagonized GABAR currents with
low affinity. The neurosteroids alphaxalone and pregnenolone sulfate
appropriately modulated GABAR currents. Zinc blocked GABAR currents with low
affinity, but lanthanum did not significantly alter NT2-N GABAR currents. Reverse
transcription PCR (RT-PCR) performed on RNA from NT2-N cells clearly detected
transcripts encoding human alpha2, alpha3, alpha5, beta3, gamma3, and pi
subtypes. The combined pharmacological and RT-PCR results are most consistent
with a single or predominant GABAR isoform composed of an alpha2 and/or alpha3
subtype combined with the beta3 and gamma3 subtypes. The data do not rule out
receptors containing combinations of alpha2 and/or alpha3 subtypes with the
alpha5 subtype or receptors with both beta1 and beta3 subtypes. The presence or
absence or the pi subunit in functionally expressed receptors could not be
determined.
PMID- 9634566
TI - Differential withdrawal of retinal axons induced by a secreted factor.
AB - To understand the development of the topographic map in the chick retinotectal
projection, we studied the long-term interactions between retinal axons and
tectal cell processes using a novel coculture system, the ryomen chamber. Both
nasal and temporal retinal axons initially grew equally well on a substrate
consisting of posterior tectal cell processes; however, subsequently most
temporal axons withdrew from this surface, whereas most nasal axons did not.
Experiments using conditioned media indicate that posterior tectal cells induced
withdrawal of the temporal axons by secreting a soluble factor. This withdrawal
seems to be distinct from the immediate repulsive effect of ephrin-A2 (ELF-1) and
ephrin-A5 (RAGS) seen in the stripe assay because (1) the withdrawal-inducing
factor was diffusible, whereas ephrin-A2 and -A5 are membrane-bound, and (2) the
withdrawal-inducing factor appeared later in development than ephrin-A2 and -A5.
Furthermore, sensitivity to the withdrawal-inducing factor decreased continuously
from the temporal to nasal retina. These results suggest that target cell-induced
axonal withdrawal may be involved during a late stage of the development of the
retinotectal map.
PMID- 9634567
TI - Blockade of glutamate-mediated activity in the developing retina perturbs the
functional segregation of ON and OFF pathways.
AB - The dendrites of ganglion cells initially ramify throughout the inner plexiform
layer of the developing retina before becoming stratified into ON or OFF
sublaminae. This ontogenetic event is thought to depend on glutamate-mediated
afferent activity, because treating the developing retina with the glutamate
analog 2-amino-4-phosphonobutyrate (APB), which hyperpolarizes ON cone bipolar
cells and rod bipolar cells, thereby preventing their release of glutamate,
effectively arrests the dendritic stratification process. To assess the
functional consequences of this manipulation, extracellular recordings were made
from single cells in the A laminae of the dorsal lateral geniculate nucleus and
from the optic tract in mature cats that had received intraocular injections of
APB during the first postnatal month. Such recordings revealed that stimulation
of the APB-treated eye evoked both ON as well as OFF discharges in 37% of the
cells tested. (As expected, when the normal eye was activated, virtually all
cells yielded only ON or OFF responses.) The proportion of ON-OFF cells found
here corresponds closely to the incidence of multistratified dendrites observed
previously in anatomical studies of APB-treated cat retinas. This suggests that
the ganglion cells with multistratified dendrites receive functional inputs from
ON as well as OFF cone bipolar cells. This interpretation is further supported by
the finding that the proportion of ON-OFF cells was very similar in the
geniculate layer innervated by the treated eye and in the optic tract. The cells
activated by the APB-treated eye were also found not to show response suppression
when flashing stimuli of increasing size were used. This suggests that exposing
the developing retina to APB perturbs the neural circuitry mediating the
antagonistic center-surround organization found in normal receptive fields. The
functional changes evident after treating the developing retina with APB suggest
that it should now be feasible to assess how the segregation of ON and OFF
retinal pathways relates to organizational features at higher levels of the
visual system, such as orientation selectivity in cortical cells.
PMID- 9634568
TI - The role of parietal cortex in verbal working memory.
AB - Neuroimaging studies of normal subjects and studies of patients with focal
lesions implicate regions of parietal cortex in verbal working memory (VWM), yet
the precise role of parietal cortex in VWM remains unclear. Some evidence (; )
suggests that the parietal cortex mediates the storage of verbal information, but
these studies and most previous ones included encoding and retrieval processes as
well as storage and rehearsal of verbal information. A recent positron emission
tomography (PET) study by isolated storage and rehearsal from other VWM processes
and did not find reliable activation in parietal cortex. This result suggests
that parietal cortex may not be involved in VWM storage, contrary to previous
proposals. However, we report two behavioral studies indicating that some of the
verbal material used by may not have required phonological representations in
VWM. In addition, we report a PET study that isolated VWM encoding, retrieval,
and storage and rehearsal processes in different PET scans and used material
likely to require phonological codes in VWM. After subtraction of appropriate
controls, the encoding condition revealed no reliable activations; the retrieval
condition revealed reliable activations in dorsolateral prefrontal, anterior
cingulate, posterior parietal, and extrastriate cortices, and the storage
condition revealed reliable activations in dorsolateral prefrontal, inferior
frontal, premotor, and posterior parietal cortices, as well as cerebellum. These
results suggest that parietal regions are part of a network of brain areas that
mediate the short-term storage and retrieval of phonologically coded verbal
material.
PMID- 9634569
TI - Effects of pedunculopontine tegmental nucleus lesions on responding for
intravenous heroin under different schedules of reinforcement.
AB - The pedunculopontine tegmental nucleus (PPTg) is believed to play important roles
in reward and learning. We examined the effect of PPTg lesions (0.5 microl of 0.1
M NMDA injected bilaterally over 10 min) on the learning of an operant response
for opiate reward. In 14 adult male Long-Evans rats, bilateral lesions of the
PPTg disrupted the acquisition of responding for intravenous heroin (0.1 mg/kg
infused at a rate of 0.25 ml/28 sec) on a fixed ratio-1 (FR-1) schedule of
reinforcement. The 12 remaining lesioned animals increased their heroin intake
over the acquisition sessions but did not reach the response levels of sham
lesioned animals on the 15th and final session. The sham- and PPTg-lesioned
animals that learned the FR-1 task exhibited similar patterns of responding
during extinction and reacquisition sessions. When tested on a progressive ratio
(PR) schedule of reinforcement, however, PPTg-lesioned animals had lower break
points than sham-lesioned animals. Asymmetric lesions, which destroyed the
majority of the nucleus in one hemisphere only, did not produce any behavioral
deficits. Rats that were lesioned after training also did not show deficits in
responding under either FR or PR schedules. These findings suggest that PPTg
lesions reduce the rewarding effect of opiates but do not disrupt the ability
either to learn an operant response or the response requirements of a PR
schedule.
PMID- 9634570
TI - Endogenous regulation of serotonin release in the hamster suprachiasmatic
nucleus.
AB - Serotonin (5-HT) has been strongly implicated in the regulation of the mammalian
circadian clock located in the suprachiasmatic nuclei (SCN). However, little is
known of the pattern of neuronal 5-HT release in the SCN or of the factors
involved in regulating its release. Using in vivo microdialysis, we demonstrated
the existence of a daily rhythm in the output of 5-HT in the SCN of freely
behaving hamsters. This rhythm was characterized by a sharp increase in release
from a nadir during late midday to peak levels at the light/dark transition.
Output declined to basal levels throughout the remainder of the night. A similar
pattern also was evident under constant darkness, with increased 5-HT output
occurring at the onset of subjective night. Locomotor activity induced by
exposure to a novel running wheel had a pronounced phase-dependent effect on 5-HT
release in the SCN, with stimulation during the light phase and suppression
during the late dark phase. Systemic application of the somatodendritic 5-HT1A
agonist BMY 7378 had a significantly greater suppressive effect on 5-HT release
in the SCN during the late dark phase compared with mid light phase, indicating
that a variation in raphe autoreceptor response may underlie the time-dependent
effects of wheel running on 5-HT release. Collectively, these results show that
the daily rhythm in output of 5-HT in the SCN is generated endogenously, and that
behavioral state can strongly influence serotonergic activity in the circadian
clock in a phase-dependent manner.
PMID- 9634571
TI - Frequency regulation of a slow rhythm by a fast periodic input.
AB - Many nervous systems contain rhythmically active subnetworks that interact
despite oscillating at widely different frequencies. The stomatogastric nervous
system of the crab Cancer borealis produces a rapid pyloric rhythm and a
considerably slower gastric mill rhythm. We construct and analyze a conductance
based compartmental model to explore the activation of the gastric mill rhythm by
the modulatory commissural neuron 1 (MCN1). This model demonstrates that the
period of the MCN1-activated gastric mill rhythm, which was thought to be
determined entirely by the interaction of neurons in the gastric mill network,
can be strongly influenced by inhibitory synaptic input from the pacemaker neuron
of the fast pyloric rhythm, the anterior burster (AB) neuron. Surprisingly, the
change of the gastric mill period produced by the pyloric input to the gastric
mill system can be many times larger than the period of the pyloric rhythm
itself. This model illustrates several mechanisms by which a fast oscillatory
neuron may control the frequency of a much slower oscillatory network. These
findings suggest that it is possible to modify the slow rhythm either by direct
modulation or indirectly by modulating the faster rhythm.
PMID- 9634572
TI - Striatal extracellular dopamine levels in rats with haloperidol-induced
depolarization block of substantia nigra dopamine neurons.
AB - Correlations between substantia nigra (SN) dopamine (DA) cell activity and
striatal extracellular DA were examined using simultaneous extracellular single
unit recordings and in vivo microdialysis performed in drug-naive rats and in
rats treated repeatedly with haloperidol (HAL). Intact rats treated with HAL for
21-28 d exhibited significantly fewer active DA cells, indicating the presence of
depolarization block (DB) in these cells. However, in rats that received surgical
implantation of the microdialysis probe followed by a 24 hr recovery period, HAL
induced DA cell DB was reversed, as evidenced by a number of active DA neurons
that was significantly higher than that in HAL-treated intact rats and similar to
that of drug-naive rats. In contrast, using a modified probe implantation
procedure that did not reverse SN DA neuron DB, we found striatal DA efflux to be
significantly lower than in controls and significantly correlated with the
reduction in DA neuron spike activity. Furthermore, although basal striatal DA
efflux was independent of SN DA cell burst-firing activity in control rats, these
variables were significantly correlated in rats with HAL-induced DA cell DB.
Therefore, HAL-induced DB of SN DA neurons is disrupted by implantation of a
microdialysis probe into the striatum using standard procedures. However, a
modified microdialysis method that allowed reinstatement of DA neuron DB revealed
that the HAL-induced inactivation of SN DA neurons was associated with
significantly lower extracellular DA levels in the striatum. Moreover, the
residual extracellular DA maintained in the presence of DB may, in part, depend
on the burst-firing pattern of the noninactivated DA neurons in the SN.
PMID- 9634573
TI - Coadministration of galanin antagonist M40 with a muscarinic M1 agonist improves
delayed nonmatching to position choice accuracy in rats with cholinergic lesions.
AB - The neuropeptide galanin is overexpressed in the basal forebrain in Alzheimer's
disease (AD). In rats, galanin inhibits evoked hippocampal acetylcholine release
and impairs performance on several memory tasks, including delayed nonmatching to
position (DNMTP). Galanin(1-13)-Pro2-(Ala-Leu)2-Ala-NH2 (M40), a peptidergic
galanin receptor ligand, has been shown to block galanin-induced impairment on
DNMTP in rats. M40 injected alone, however, does not improve DNMTP choice
accuracy deficits in rats with selective cholinergic immunotoxic lesions of the
basal forebrain. The present experiments used a strategy of combining M40 with an
M1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin 192IgG
saporin. Coadministration of intraventricular M40 with intraperitoneal 3-(3-S-n
pentyl-1,2,5-thiadiazol-4-yl)-1,2,5, 6-tetrahydro-1-methylpyridine (TZTP), an M1
agonist, improved choice accuracy significantly more than a threshold dose of
TZTP alone. These results suggest that a galanin antagonist may enhance the
efficacy of cholinergic treatments for the cognitive deficits of AD.
PMID- 9634574
TI - Small changes in ambient temperature cause large changes in 3,4
methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core
body temperature in the rat.
AB - The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of
abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMA
engendered neurotoxicity has been shown to be affected by both ambient
temperature and core body temperature. We now report that small (2 degreesC)
changes in ambient temperature produce changes in core temperature in MDMA
treated rats, but the same changes in ambient temperature do not affect core
temperature of saline-treated animals. Furthermore, increases in core temperature
of MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40
mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or
30 degreesC using a novel temperature measurement apparatus that controls ambient
temperature +/-0.5 degrees C. Two weeks after MDMA treatment, the rats were
killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as
a measure of neurotoxicity. Rats treated with MDMA at 20 and 22 degrees C showed
a hypothermic core temperature response. Treatment with MDMA at 28 and 30
degreesC produced a hyperthermic response. At ambient temperatures of 20-24
degrees C, neurotoxicity was not observed in the frontal cortex, somatosensory
cortex, hippocampus, or striatum. At ambient temperatures of 26-30 degrees C,
neurotoxicity was seen and correlated with core temperature in all regions
examined. These data indicate that ambient temperature has a significant affect
on MDMA neurotoxicity, core temperature, and thermoregulation in rats. This
finding has implications on both the temperature dependence of the mechanism of
MDMA neurotoxicity and human use because fatal hyperthermia is associated with
MDMA use in humans.
PMID- 9634575
TI - Electrophysiology of the hippocampal and amygdaloid projections to the nucleus
accumbens of the rat: convergence, segregation, and interaction of inputs.
AB - The nucleus accumbens (Nacb) receives inputs from hippocampus and amygdala but it
is still unclear how these inputs are functionally organized and may interact.
The interplay between these input pathways was examined using
electrophysiological tools in the rat, in vivo, under halothane anesthesia. After
fornix/fimbria stimulation (Fo/Fi, subicular projection fibers to the Nacb), mono
and polysynaptically driven single units were recorded in the medial shell/core
regions of the Nacb and in the ventromedial caudate putamen. Monosynaptically
driven neurons by basolateral amygdala (BLA) stimulation were found in the medial
shell/core and in the ventrolateral shell/core regions. In the areas of
convergence (medial shell/core), paired activation of BLA followed by that of
Fo/Fi resulted in an enhancement of the Fo/Fi response, whereas stimulation in
the reverse order, Fo/Fi followed by BLA, led to a depression of the BLA
response. In addition to these patterns of interactions, the tetanization of the
Fo/Fi to Nacb pathway caused a homosynaptic decremental (long-term) potentiation
in the Nacb, accompanied by a heterosynaptic (long-term) depression of the
nontetanized BLA to Nacb pathway. We postulate that the hippocampal inputs may
close a "gate" for the amygdala inputs, whereas the gate is opened for the
hippocampus inputs by previous amygdalar activity. These opposite effects on the
Nacb neuronal populations should be taken into account when interpreting
behavioral phenomena, particularly with respect to the contrasting effects of the
amygdala and the hippocampus in locomotion and place learning.
PMID- 9634576
TI - Defense responses in plants and animals--more of the same.
PMID- 9634577
TI - Transposon tagging of the Defective embryo and meristems gene of tomato.
AB - The shoot and root apical meristems (SAMs and RAMs, respectively) of higher
plants are mechanistically and structurally similar. This has led previously to
the suggestion that the SAM and RAM represent modifications of a fundamentally
homologous plan of organization. Despite recent interest in plant development,
especially in the areas of meristem regulation, genes specifically required for
the function of both the SAM and RAM have not yet been identified. Here, we
report on a novel gene, Defective embryo and meristems (Dem), of tomato. This
gene is required for the correct organization of shoot apical tissues of
developing embryos, SAM development, and correct cell division patterns and
meristem maintenance in roots. Dem was cloned using transposon tagging and shown
to encode a novel protein of 72 kD with significant homology to YNV2, a protein
of unknown function of Saccharomyces cerevisiae. Dem is expressed in root and
shoot meristems and organ primordia but not in callus. The expression pattern of
Dem mRNA in combination with the dem mutant phenotype suggests that Dem plays an
important role within apical meristems.
PMID- 9634578
TI - An Arabidopsis mutant hypersensitive to red and far-red light signals.
AB - A new mutant called psi2 (for phytochrome signaling) was isolated by screening
for elevated activity of a chlorophyll a/b binding protein-luciferase (CAB2-LUC)
transgene in Arabidopsis. This mutant exhibited hypersensitive induction of CAB1,
CAB2, and the small subunit of ribulose-1,5-bisphosphate carboxylase (RBCS)
promoters in the very low fluence range of red light and a hypersensitive
response in hypocotyl growth in continuous red light of higher fluences. In
addition, at high- but not low-light fluence rates, the mutant showed light
dependent superinduction of the pathogen-related protein gene PR-1a and developed
spontaneous necrotic lesions in the absence of any pathogen. Expression of genes
responding to various hormone and environmental stress pathways in the mutant was
not significantly different from that of the wild type. Analysis of double
mutants demonstrated that the effects of the psi2 mutation are dependent on both
phytochromes phyA and phyB. The mutation is recessive and maps to the bottom of
chromosome 5. Together, our results suggest that PSI2 specifically and negatively
regulates both phyA and phyB phototransduction pathways. The induction of cell
death by deregulated signaling pathways observed in psi2 is reminiscent of
retinal degenerative diseases in animals and humans.
PMID- 9634579
TI - Srchi13, a novel early nodulin from Sesbania rostrata, is related to acidic class
III chitinases.
AB - On the tropical legume Sesbania rostrata, stem-borne nodules develop after
inoculation of adventitious root primordia with the microsymbiont Azorhizobium
caulinodans. A cDNA clone, Srchi13, with homology to acidic class III chitinase
genes, corresponds to an early nodulin gene with transiently induced expression
during nodule ontogeny. Srchi13 transcripts accumulated strongly 2 days after
inoculation, decreased from day 7 onward, and disappeared in mature nodules.
Induction was dependent on Nod factor-producing bacteria. Srchi13 was expressed
around infection pockets, in infection centra, around the developing nodule and
its vascular bundles, and in uninfected cells of the central tissue. The specific
and transient transcript accumulation together with the lipochitooligosaccharide
degradation activity of the recombinant protein hint at a role of Srchi13 in
normal nodule ontogeny by limiting the action of Nod factors.
PMID- 9634580
TI - Inactivation of the sapA to sapF locus of Erwinia chrysanthemi reveals common
features in plant and animal bacterial pathogenesis.
AB - We investigated the role in pathogenesis of bacterial resistance to plant
antimicrobial peptides. The sapA to sapF (for sensitive to antimicrobial
peptides) operon from the pathogenic bacterium Erwinia chrysanthemi has been
characterized. It has five open reading frames that are closely related (71%
overall amino acid identity) and are in the same order as those of the sapA to
sapF operon from Salmonella typhimurium. An E. chrysanthemi sap mutant strain was
constructed by marker exchange. This mutant was more sensitive than was the wild
type to wheat alpha-thionin and to snakin-1, which is the most abundant
antimicrobial peptide from potato tubers. This mutant was also less virulent than
was the wild-type strain in potato tubers: lesion area was 37% that of the
control, and growth rate was two orders of magnitude lower. These results
indicate that the interaction of antimicrobial peptides from the host with the
sapA to sapF operon from the pathogen plays a similar role in animal and in plant
bacterial pathogenesis.
PMID- 9634581
TI - GOLDEN 2: a novel transcriptional regulator of cellular differentiation in the
maize leaf.
AB - The differentiation of distinct cell types within the leaf is essential for
normal plant development. We characterized previously a transposon-induced mutant
of maize (bundle sheath defective1) that disrupts the differentiation of a single
photosynthetic cell type in the leaf. In this study, we show that this mutation
is allelic to golden2 (g2), a lesion first reported 70 years ago. We cloned G2 by
using Suppressor-mutator as a molecular tag. The gene encodes a 2. 2-kb
transcript that is present throughout the wild-type leaf but is most abundant in
C4 leaf blade tissue. Gene sequence data showed the existence of a bipartite
nuclear localization signal encoded by the first exon, and we determined that G2
reporter gene fusions are targeted to the nucleus in onion epidermal cells.
Further sequence analysis indicated the presence of a novel motif within the
deduced protein sequence that shares features with TEA DNA binding domains.
Therefore, we propose that G2 acts as a novel transcriptional regulator of
cellular differentiation in the maize leaf.
PMID- 9634582
TI - Initiation and maintenance of virus-induced gene silencing
AB - The phytoene desaturase (PDS) gene of Nicotiana benthamiana was silenced in
plants infected with potato virus X (PVX) vectors carrying PDS inserts, and a
green fluorescent protein (GFP) transgene was silenced in plants infected with
PVX-GFP. This virus-induced gene silencing (VIGS) is post-transcriptional and
cytoplasmic because it is targeted against exons rather than introns of PDS RNA
and against viral RNAs. Although PDS and GFP RNAs are most likely targeted
through the same mechanism, the VIGS phenotypes differed in two respects. PDS
mRNA was targeted by VIGS in all green tissue of the PVX-PDS-infected plant,
whereas PVX-PDS was not affected. In contrast, VIGS of the GFP was targeted
against PVX-GFP. Initially, VIGS of the GFP was initiated in all green tissues,
as occurred with PDS VIGS. However, after 30 days of infection, the GFP VIGS was
no longer initiated in newly emerging leaves, although it was maintained in
tissue in which it had already been initiated. Based on these analyses, we
propose a model for VIGS in which the initiation of VIGS is dependent on the
virus and maintenance of it is virus independent.
PMID- 9634583
TI - An Arabidopsis mutant with enhanced resistance to powdery mildew.
AB - We have identified an Arabidopsis mutant that displays enhanced disease
resistance to the fungus Erysiphe cichoracearum, causal agent of powdery mildew.
The edr1 mutant does not constitutively express the pathogenesis-related genes PR
1, BGL2, or PR-5 and thus differs from previously described disease-resistant
mutants of Arabidopsis. E. cichoracearum conidia (asexual spores) germinated
normally and formed extensive hyphae on edr1 plants, indicating that the initial
stages of infection were not inhibited. Production of conidiophores on edr1
plants, however, was <16% of that observed on wild-type Arabidopsis. Reduction in
sporulation correlated with a more rapid induction of defense responses.
Autofluorescent compounds and callose accumulated in edr1 leaves 3 days after
inoculation with E. cichoracearum, and dead mesophyll cells accumulated in edr1
leaves starting 5 days after inoculation. Macroscopic patches of dead cells
appeared 6 days after inoculation. This resistance phenotype is similar to that
conferred by "late-acting" powdery mildew resistance genes of wheat and barley.
The edr1 mutation is recessive and maps to chromosome 1 between molecular markers
ATEAT1 and NCC1. We speculate that the edr1 mutation derepresses multiple defense
responses, making them more easily induced by virulent pathogens.
PMID- 9634584
TI - Characterization of microtubule binding domains in the Arabidopsis kinesin-like
calmodulin binding protein.
AB - The kinesin-like calmodulin binding protein (KCBP) is a new member of the kinesin
superfamily that appears to be present only in plants. The KCBP is unique in its
ability to interact with calmodulin in a Ca2+-dependent manner. To study the
interaction of the KCBP with microtubules, we expressed different regions of the
Arabidopsis KCBP and used the purified proteins in cosedimentation assays with
microtubules. The motor domain with or without the calmodulin binding domain
bound to microtubules. The binding of the motor domain containing the calmodulin
binding region to microtubules was inhibited by Ca2+-calmodulin. This Ca2+
calmodulin regulation of motor domain interactions with microtubules was
abolished in the presence of antibodies specific to the calmodulin binding
region. In addition, the binding of the motor domain lacking the calmodulin
binding region to microtubules was not inhibited in the presence of Ca2+
calmodulin, suggesting an essential role for the calmodulin binding region in
Ca2+-calmodulin modulation. Results of the cosedimentation assays with the N
terminal tail suggest the presence of a second microtubule binding site on the
KCBP. However, the interaction of the N-terminal tail region of the KCBP with
microtubules was insensitive to ATP. These data on the interaction of the KCBP
with microtubules provide new insights into the functioning of the KCBP in
plants.
PMID- 9634585
TI - A potential signaling role for profilin in pollen of Papaver rhoeas.
AB - Regulation of pollen tube growth is known to involve alterations in intracellular
calcium levels and phosphoinositide signaling, although the mechanisms involved
are unclear. However, it appears likely that pollination events involve a complex
interplay between signaling pathways and components of the actin cytoskeleton in
pollen. In many eukaryotic cells, actin binding proteins function as stimulus
response modulators, translating signals into alterations in the cytoplasmic
architecture. In this study, we examined whether profilin, which is a member of
this class of signaling intermediate, might play a similar role in pollen. We
have analyzed the functional properties of native profilin from pollen of Papaver
rhoeas and have investigated the effects of profilin on the phosphorylation of
pollen proteins in vitro by adding a slight excess of profilin to cytosolic
pollen extracts. We present clear evidence that profilin interacts with soluble
pollen components, resulting in dramatic alterations in the phosphorylation of
several proteins. We also show, albeit in vitro, the involvement of profilin in
modulating the activity of a signaling component(s) affecting protein
phosphorylation. Our data, which suggest that pollen profilin can regulate actin
based cytoskeletal protein assembly and protein kinase or phosphatase activity,
indicate a possible role for the involvement of profilin in signaling pathways
that may regulate pollen tube growth.
PMID- 9634586
TI - Pollen profilin function depends on interaction with proline-rich motifs.
AB - The actin binding protein profilin has dramatic effects on actin polymerization
in vitro and in living cells. Plants have large multigene families encoding
profilins, and many cells or tissues can express multiple profilin isoforms.
Recently, we characterized several profilin isoforms from maize pollen for their
ability to alter cytoarchitecture when microinjected into living plant cells and
for their association with poly-L-proline and monomeric actin from maize pollen.
In this study, we characterize a new profilin isoform from maize, which has been
designated ZmPRO4, that is expressed predominantly in endosperm but is also found
at low levels in all tissues examined, including mature and germinated pollen.
The affinity of ZmPRO4 for monomeric actin, which was measured by two independent
methods, is similar to that of the three profilin isoforms previously identified
in pollen. In contrast, the affinity of ZmPRO4 for poly-L-proline is nearly
twofold higher than that of native pollen profilin and the other recombinant
profilin isoforms. When ZmPRO4 was microinjected into plant cells, the effect on
actin-dependent nuclear position was significantly more rapid than that of
another pollen profilin isoform, ZmPRO1. A gain-of-function mutant (ZmPRO1-Y6F)
was created and found to enhance poly-L-proline binding activity and to disrupt
cytoarchitecture as effectively as ZmPRO4. In this study, we demonstrate that
profilin isoforms expressed in a single cell can have different effects on actin
in living cells and that the poly-L-proline binding function of profilin may have
important consequences for the regulation of actin cytoskeletal dynamics in plant
cells.
PMID- 9634587
TI - Identification of a negative regulator of gibberellin action, HvSPY, in barley.
AB - To broaden our understanding of the molecular mechanisms of gibberellin (GA)
action, we isolated a spindly clone (HvSPY) from barley cultivar Himalaya and
tested whether the HvSPY protein would modulate GA action in barley aleurone. The
HvSPY cDNA showed high sequence identity to Arabidopsis SPY along its entire
length, and the barley protein functionally complemented the spy-3 mutation.
HvSPY and SPY proteins showed sequence relatedness with animal O-linked N
acetylglucosamine transferases (OGTs), suggesting that they may also have OGT
activity. HvSPY has a locus distinct from that of Sln, a mutation that causes the
constitutive GA responses of slender barley, which phenotypically resembles
Arabidopsis spy mutants. The possibility that the HvSPY gene encodes a negative
regulator of GA action was tested by expressing HvSPY in a barley aleurone
transient assay system. HvSPY coexpression largely abolished GA3-induced activity
of an alpha-amylase promoter. Surprisingly, HvSPY coexpression increased reporter
gene activity from an abscisic acid (ABA)-inducible gene promoter (dehydrin),
even in the absence of exogenous ABA. These results show that HvSPY modulates the
transcriptional activities of two hormonally regulated promoters: negatively for
a GA-induced promoter and positively for an ABA-induced promoter.
PMID- 9634588
TI - Two genes with similarity to bacterial response regulators are rapidly and
specifically induced by cytokinin in Arabidopsis.
AB - Cytokinins are central regulators of plant growth and development, but little is
known about their mode of action. By using differential display, we identified a
gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that
is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated
within 10 min by the exogenous application of cytokinin, and this induction did
not require de novo protein synthesis. IBC6 was not induced by other plant
hormones or by light. A second Arabidopsis gene with a sequence highly similar to
IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with
somewhat slower kinetics and to a lesser extent. The pattern of expression of the
two genes was similar, with higher expression in leaves, rachises, and flowers
and lower transcript levels in roots and siliques. Sequence analysis revealed
that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component
response regulators. This homology, coupled with previously published work on the
CKI1 histidine kinase homolog, suggests that these proteins may play a role in
early cytokinin signaling.
PMID- 9634589
TI - PAD4 functions upstream from salicylic acid to control defense responses in
Arabidopsis.
AB - The Arabidopsis PAD4 gene was previously shown to be required for synthesis of
camalexin in response to infection by the virulent bacterial pathogen Pseudomonas
syringae pv maculicola ES4326 but not in response to challenge by the non-host
fungal pathogen Cochliobolus carbonum. In this study, we show that pad4 mutants
exhibit defects in defense responses, including camalexin synthesis and
pathogenesis-related PR-1 gene expression, when infected by P. s. maculicola ES4
326. No such defects were observed in response to infection by an isogenic
avirulent strain carrying the avirulence gene avrRpt2. In P. s. maculicola ES4
326-infected pad4 plants, synthesis of salicylic acid (SA) was found to be
reduced and delayed when compared with SA synthesis in wild-type plants.
Moreover, treatment of pad4 plants with SA partially reversed the camalexin
deficiency and PR-1 gene expression phenotypes of P. s. maculicola ES4 326
infected pad4 plants. These findings support the hypothesis that PAD4 acts
upstream from SA accumulation in regulating defense response expression in plants
infected with P. s. maculicola ES4 326. A working model of the role of PAD4 in
governing expression of defense responses is presented.
PMID- 9634590
TI - Sorting of phaseolin to the vacuole is saturable and requires a short C-terminal
peptide.
AB - Phaseolin, one of the major legume proteins for human nutrition, is a trimeric
glycoprotein of the 7S class that accumulates in the protein storage vacuoles of
common bean. Phaseolin is cotranslationally introduced into the lumen of the
endoplasmic reticulum; from there, it is transported through the Golgi complex to
the storage vacuoles. Phaseolin is also transported to the vacuole in vegetative
tissues of transgenic plants. By transient and permanent expression in tobacco
leaf cells, we show here that vacuolar sorting of phaseolin is saturable and that
saturation leads to Golgi-mediated secretion from the cell. A mutated phaseolin,
in which the four C-terminal residues (Ala, Phe, Val, and Tyr) were deleted,
efficiently formed trimers but was secreted entirely outside of the cells in
transgenic tobacco leaves, indicating that the deleted sequence contains
information necessary for interactions with the saturable vacuolar sorting
machinery. In the apoplast, the secreted phaseolin remained intact; this is
similar to what occurs to wild-type phaseolin in bean storage vacuoles, whereas
in vegetative vacuoles of transgenic plants, the storage protein is fragmented.
PMID- 9634591
TI - The Arabidopsis abscisic acid response locus ABI4 encodes an APETALA 2 domain
protein.
AB - Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects
in seed development, including decreased sensitivity to ABA inhibition of
germination and altered seed-specific gene expression. This phenotype is
consistent with a role for ABI4 in regulating seed responses to ABA and/or seed
specific signals. We isolated the ABI4 gene by positional cloning and confirmed
its identity by complementation analysis. The predicted protein product shows
homology to a plant-specific family of transcriptional regulators characterized
by a conserved DNA binding domain, the APETALA 2 domain. The single mutant allele
identified has a single base pair deletion, resulting in a frameshift that should
disrupt the C-terminal half of the protein but leave the presumed DNA binding
domain intact. Expression analyses showed that despite the seed-specific nature
of the mutant phenotype, ABI4 expression is not seed specific.
PMID- 9634592
TI - Dissection of the fusarium I2 gene cluster in tomato reveals six homologs and one
active gene copy.
AB - The I2 locus in tomato confers resistance to race 2 of the soil-borne fungus
Fusarium oxysporum f sp lycopersici. The selective restriction fragment
amplification (AFLP) positional cloning strategy was used to identify I2 in the
tomato genome. A yeast artificial chromosome (YAC) clone covering approximately
750 kb encompassing the I2 locus was isolated, and the AFLP technique was used to
derive tightly linked AFLP markers from this YAC clone. Genetic complementation
analysis in transgenic R1 plants using a set of overlapping cosmids covering the
I2 locus revealed three cosmids giving full resistance to F. o. lycopersici race
2. These cosmids shared a 7-kb DNA fragment containing an open reading frame
encoding a protein with similarity to the nucleotide binding site leucine-rich
repeat family of resistance genes. At the I2 locus, we identified six additional
homologs that included the recently identified I2C-1 and I2C-2 genes. However,
cosmids containing the I2C-1 or I2C-2 gene could not confer resistance to plants,
indicating that these members are not the functional resistance genes. Alignments
between the various members of the I2 gene family revealed two significant
variable regions within the leucine-rich repeat region. They consisted of
deletions or duplications of one or more leucine-rich repeats. We propose that
one or both of these leucine-rich repeats are involved in Fusarium wilt
resistance with I2 specificity.
PMID- 9634593
TI - A role for vesicles in human basophil secretion.
AB - The evidence for vesicular transport as a mechanism for secretion by human
basophils is reviewed. Initially, direct electron-microscopic inspection of
experimentally produced and sequentially biopsied contact allergy skin lesions
revealed a unique form of secretion termed piecemeal degranulation, characterized
by the slow emptying of secretory granule contents (with retention of empty
containers) in the absence of extrusion of entire granules. Budding of small
vesicles to/from secretory granules was observed, and cytoplasmic vesicles were
abundant. A generalized degranulation model was proposed to unify classical
regulated secretion and this new form of secretion. Investigation of the
mechanism(s) of secretion from human basophils required the development of
numerous tools and resources. Chief among these were: (a) isolation and
purification of circulating basophils; (b) identification of specific growth
factors to increase the supply of this rare granulocyte; (c) understanding of
secretogogue mechanisms and reliable analyses of secreted basophil products; and
(d) development of ultrastructural preparations allowing imaging of small
vesicles and quantifiable small electron-dense tags for granule materials in
small vesicles. Applications of these tools to well-defined models of basophil
secretion have established a role for vesicles as a mechanism for effecting
secretion of histamine and the Charcot-Leyden crystal protein from activated
human basophils.
PMID- 9634595
TI - Cellular localization of neuropeptide Y mRNA and peptide in the brain of the
Japanese quail and domestic chicken.
AB - Neuropeptide Y (NPY) has been implicated in the control of a number of
physiological functions in birds including food intake and reproduction. In the
present study, sites of NPY synthesis were localized in the brains of Japanese
quail and domestic chickens by in situ hybridization histochemistry using a
digoxigenin-labelled riboprobe. NPY mRNA was detected in three main cell groups
in both species. The most prominent group was associated with structures in the
lateral thalamus including the anterior lateral thalamic nucleus, lateral
forebrain bundle, rotund nucleus, pretectal nucleus and occipitomesencephalic
tract. Other major cell groups were detected in the hippocampus, and in the
caudal linear nucleus and raphe nucleus of the brainstem. NPY mRNA was also
present in the piriform cortex and taenial nucleus. Double-labelling of NPY mRNA
and peptide was demonstrated in individual cells of the hippocampal, thalamic and
brainstem cell groups, suggesting that NPY is synthesized and stored in these
areas. However, the identity of other cell groups, notably in the hyperstriatal,
archistriatal and neostriatal regions of the telencephalon, which exhibit NPY
immunoreactive cell bodies but no NPY mRNA, remains to be determined.
PMID- 9634594
TI - Regulated expression of neurogenic basic helix-loop-helix transcription factors
during differentiation of the immortalized neuronal progenitor cell line HC2S2
into neurons.
AB - Expression of nine neurogenic basic helix-loop-helix (bHLH) transcription factors
was examined in an immortalized neuronal progenitor cell line HC2S2, which
differentiates into neurons after suppression of the v-myc expression with
tetracycline. Expression of MASH-1, NeuroD, NeuroD-related factor (NDRF) and HES
1 was demonstrated in HC2S2 cells by Northern blot analysis using total RNA.
Expression of MASH-1 mRNA was downregulated upon differentiation of HC2S2 cells
into mature neurons. In contrast, NeuroD and NDRF mRNA expression was maintained
all through the differentiation. The expression of HES-1, a negative regulator of
the neuronal differentiation, was upregulated temporarily in accordance with the
suppression of the v-myc expression and was downregulated upon the
differentiation of HC2S2 cells into neurons. The reduced expression of HES-1 mRNA
in undifferentiated HC2S2 cells may be explained by the transcriptional
suppression of HES-1 by the myc oncoprotein. The above data imply that both HES-1
and MASH-1 need to be downregulated at the time of accomplishment of the terminal
differentiation into mature neurons and that NeuroD and NDRF participate in the
regulatory process of the terminal differentiation in combination.
PMID- 9634596
TI - Confocal laser scanning and electron-microscopic analyses of the relationship
between VIP-like and GnRH-like-immunoreactive neurons in the lateral septal
preoptic area of the pigeon.
AB - The lateral septum and the preoptic area of birds comprise neurons immunoreactive
(ir) for vasoactive intestinal polypeptide (VIP) and gonadotropin-releasing
hormone (GnRH). By use of immunohistochemical single- and double-labeling
techniques, we have investigated the distribution and the connections of these
two types of peptidergic neurons in the lateral septal-preoptic area of the
pigeon at both the light- and electron-microscopic levels. An accumulation of VIP
like-ir neurons, some of which are cerebrospinal fluid-contacting neurons, is
found in the area adjacent to the ventromedial walls of the lateral ventricles in
the lateral septum corresponding to the medial part of the lateral septal organ.
VIP-like-ir terminals are scattered throughout the lateral septal-preoptic area,
which also contains GnRH-like-ir cell bodies. The number of GnRH-like-ir cell
bodies in the lateral septum is smaller than that of the VIP-like-ir neurons.
GnRH-like-ir cells have a simple bipolar or multipolar shape and a beaded axon
that emerges from the soma or one of the proximal dendrites. Confocal laser
scanning microscopy has shown VIP-like-ir terminals in close apposition to GnRH
like-ir cell bodies in the lateral septal-preoptic area. Furthermore, the
electron-microscopic double-immunolabeling has revealed synaptic contacts between
VIP-like-ir axon terminals and GnRH-like-ir cell bodies or dendrites. These
contacts, however, do not show synaptic specializations. The present results
suggest that functional interactions take place between VIP and GnRH neurons in
the lateral septal-preoptic area of the pigeon and that these interactions are
involved in mediating photoperiodic responses.
PMID- 9634597
TI - Organization of atrial natriuretic factor-like immunoreactive system in the brain
of the frog Rana esculenta during development.
AB - Immunocytochemical distribution of the atrial natriuretic factor (ANF) has been
studied in the brain and pituitary of the anuran Rana esculenta during
development and in juvenile animals. Using human ANF and rat alpha-ANF antisera,
immunoreactive cell bodies and nerve fibers were revealed in stage II-III
tadpoles and in successive larval stages. Soon after hatching, stages II-III, the
ANF-like-immunoreactive elements were confined to the preoptic area-median
eminence complex. During successive stages of development, new groups of ANF
immunoreactive cell bodies appeared. In larval stage VI, immunoreactive perikarya
were found in the rostral part of the anteroventral area of the thalamus and
numerous ANF-like-immunoreactive cells appeared in the pars distalis of the
pituitary. In larval stages XIV and XVIII, the distribution of ANF
immunoreactivity was virtually similar. The ANF-immunoreactive cells in the
preoptic nucleus and in the pituitary pars distalis were comparatively more
abundant than in stage VI. During the metamorphic climax (stages XXI-XXII), a new
group of ANF-immunoreactive cell bodies appeared in the rostral part of the
ventrolateral area of the thalamus. During this stage, ANF-immunoreactive fiber
projections were found in the pars intermedia for the first time. However, the
pars distalis cells were very weakly immunofluorescent. The pattern of ANF
immunoreactivity in the brain of juvenile animals was very similar to that
described for stages XXI and XXII, whereas the pars distalis cells showed no
immunoreactivity. It is conceivable that, early during development, ANF-related
peptides may be involved in the regulation of pituitary secretion by means of
autocrine mechanisms or may act as a classic pituitary hormone.
PMID- 9634598
TI - Adenylyl cyclase co-distribution with the CaBPs, calbindin-D28 and calretinin,
varies with cell type: assessment with the fluorescent dye, BODIPY forskolin, in
enteric ganglia.
AB - The aims of the present study were: (1) to evaluate BODIPY forskolin as a
suitable fluorescent marker for membrane adenylyl cyclase (AC) in living enteric
neurons of the guinea-pig ileum; (2) to test the hypothesis that AC is
distributed in several subpopulations of enteric neurons; (3) to test the
hypothesis that the distribution of AC in the myenteric plexus is not unique to
AH/Type 2 neurons. BODIPY forskolin was used to assess the co-distribution of AC
in ganglion cells expressing the specific calcium-binding proteins (CaBPs),
calretinin, calbindin-D28, and s-100. Cultured cells or tissues were incubated
with 10 microM BODIPY forskolin for 30 min and fluorescent labeling was monitored
by using laser scanning confocal microscopy. BODIPY forskolin stained the cell
soma, neurites, and nerve varicosities of Dogiel Type I or II neurons. About 99%
of myenteric and 27% of submucous ganglia contained labeled neurons. About 14% of
myenteric and 3% of submucous glia with immunoreactivity for s-100 protein
displayed BODIPY forskolin fluorescence. BODIPY forskolin differentially labeled
myenteric neurons immunoreactive for calbindin-D28 (80%) and calretinin (17%).
The majority (63%) of BODIPY forskolin-labeled myenteric neurons displayed no
immunoreactivity for either CaBP. In submucous ganglia, the dye labeled 44.6% of
calretinin-immunoreactive neurons, representing 21% of all labeled neurons; it
also labeled varicose nerve fibers running along blood vessels. AC thus exists in
myenteric Dogiel type II/AH neurons, enteric cholinergic S/Type 1 neurons, and
other unidentified non-cholinergic S/Type 1 neurons. Our data also support the
hypothesis that AC is expressed in distinct functional subpopulations of AH and S
neurons in enteric ganglia, and show that BODIPY forskolin is a suitable marker
for AC in immunofluorescence co-distribution studies involving living cells or
tissues.
PMID- 9634599
TI - Plasticity of Congo red staining displayed by subpopulations of neurons within
the rat central nervous system.
AB - We document the presence of subpopulations of neurons within the rat central
nervous system that are labelled with a new Congo red staining technique. These
neurons (CR neurons) show shrunken somata, and smaller and darker nuclei than
Congo red-negative cells (non-CR cells). With the Bielschowsky and the cresyl
violet Nissl staining methods, two comparable subpopulations of cells can be
distinguished by the same morphometrical criteria as those used for CR and non-CR
cells. CR neurons are located preferentially in some brain regions while in
others they are virtually absent. Their distribution and proportion varied
greatly from animal to animal and after particular treatments. Injections of
water that damaged the hippocampal dentate gyrus, cortical lesions or eye
enucleation decreased the number of CR-cells in the CA1 subfield, reflected in a
shift from the CR-staining subclass to the non-CR subclass. Treatment with 200
mg/kg of CDP-choline also significantly reduced the number of CR cells observed
in CA1. In the red nucleus, CR neurons showed a characteristic distribution of
beta-amyloid precursor protein (APP) immunoreactivity. The population of
dendrites immunolabelled for microtubule-associated protein 2 was markedly
decreased in the areas of the hippocampus with high numbers of CR cells.
Therefore, it is proposed that neurons labelled with the present Congo red
technique might be in a reversible degenerative state or represent a particular
physiological state in some areas of the central nervous system.
PMID- 9634600
TI - Light- and electron-microscopic study of the distribution of axons containing
substance P and the localization of neurokinin-1 receptor in bone.
AB - Substance P (SP) is a neuropeptide that is released from axons of sensory neurons
and causes signal transduction through the activation of the neurokinin-1
receptor (NK1-R). The present study demonstrates the distribution of SP-like
immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue
using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly
found near the trabecular bone in the temporal bone marrow, but they were only
sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1
Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In
the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive
products of NK1-Rs were distributed close to the plasma membrane. At the electron
microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole
cytoplasm, except for the clear zone of the osteoclasts, and in pit-like
structures along the plasma membrane. The NK1-R-immunoreactive structures in the
cytoplasm were divided into two types of organelles, consisting of vesicular and
vacuolar structures (probably transport vesicles and early endosomes). In the
osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was
fewer than in the osteoclasts. These results thus suggest that SP secreted by the
sensory axons could directly modulate bone metabolism via NK1-Rs.
PMID- 9634601
TI - Expression pattern for adrenomedullin during pancreatic development in the rat
reveals a common precursor with other endocrine cell types.
AB - Adrenomedullin is an alpha-amidated 52-amino acid peptide involved in many
physiological actions, among others the regulation of insulin secretion. Using
immunohistochemical methods, we found that adrenomedullin immunoreactivity first
appears at day 11.5 of embryonic development in the rat, coinciding with the
appearance of pancreatic glucagon. The early appearance of adrenomedullin in the
developing pancreas may indicate an active involvement in either the
morphogenesis of the organ or its endocrine/paracrine/autocrine hormone
regulation during intrauterine life. We also investigated the pattern of
colocalizations of adrenomedullin with the other pancreatic hormones. At some
point during development all the cell types express adrenomedullin, progressively
evolving towards the adult pattern where only the pancreatic polypeptide cells
contain a strong immunoreactivity for adrenomedullin. At this point the remaining
cells of the islet are, in general, weakly stained. This sequential and time
dependent expression of adrenomedullin suggests a tight regulation similar to
that observed for other modulatory substances responsible for embryonic
morphogenesis.
PMID- 9634602
TI - Protein and fatty acid composition of caveolae from apical plasmalemma of aortic
endothelial cells.
AB - In endothelial cells (EC), caveolae or plasmalemmal vesicles (PVs) represent a
structurally and biochemically specialized membrane microdomain. Since few data
are available on the biochemical composition of PVs of large vessel endothelium,
we have designed experiments to isolate this domain and to analyze its chemical
components. A highly purified apical membrane fraction was obtained from cultured
bovine aortic EC by using cationic colloidal silica (silica-ap), or the EC were
surface-radioiodinated and a cell homogenate was prepared. Detergent treatment
(Triton X-100; TX) and mechanical disruption of both the silica-ap fraction and
cell homogenate followed by ultracentrifugation on a sucrose gradient gave
detergent-soluble and detergent-insoluble membranous fractions. The lowest
density TX-insoluble fraction appeared morphologically as distinct vesicles
(caveolae; 60 nm average diameter; PVs fraction). Biochemical characterization of
the PVs fraction (by comparison with the soluble fraction) revealed the presence,
at high concentration, of specific caveolar markers, viz., caveolin (both
isoforms, the 24-kDa form being conspicuously more abundant) and Ca2+-ATPase. By
contrast, angiotensin-converting enzyme and alkaline phosphodiesterase were
present almost exclusively in the TX-soluble fraction. The glycoproteins in the
PVs fraction were of apparent molecular weights 52, 68, 95, and 114 kDa. Analysis
of the fatty acid composition revealed more palmitoleic and stearic acid in the
PVs fraction then in the TX-soluble fraction. Thus, in comparison with the
plasmalemma proper, the PVs fraction (1) is detergent-insoluble; (2) contains
caveolin in two isoforms; (3) contains Ca2+-ATPase at high concentration; (4)
contains a set of specific glycoproteins; and (5) is enriched in palmitoleic and
stearic acids.
PMID- 9634603
TI - Bovine mast cells: distribution, density, heterogeneity, and influence of
fixation techniques.
AB - Mast cells can be distinguished according to various characteristics: rodent mast
cells have been subtyped by histochemical criteria, whereas canine and human mast
cells have been classified according to their proteases. Comparisons of mast
cells from different species have therefore resulted in contradictory and
confusing opinions on mast cell heterogeneity. Thus, it is essential to obtain
species-specific data on mast cell density and heterogeneity. The present study
was carried out to determine the physiological distribution of mast cell numbers
and types in bovines according to tissue location, staining, and fixation
methods. Samples were fixed in formalin or Carnoy's fluid. The average number of
mast cells was determined by using a metachromatic staining method. Protease
content of mast cells was examined with a double-enzyme-immunohistochemical
staining technique. Three mast cell subtypes were distinguished: T-, TC-, and C
mast cells. The T-mast cell was the predominant subtype in nearly all
investigated organs and tissue locations. Only tryptase-positive mast cells could
be demonstrated in bovine skin and uterus. No chymase activity was found in these
organs, regardless of the fixation type. A larger number of mast cells was
observed after fixation in Carnoy's fluid. The three different mast cell subtypes
were only demonstrated in formalin-fixed tissue; chymase-positive mast cells were
not found after fixation in Carnoy's fluid. Increasing experimental data suggest
that mast cell subtypes have different functions in promoting and modulating
inflammation and in remodeling the extracellular matrix. Since mast cell tryptase
and chymase have different functional properties, these results may clarify the
different reaction patterns observed in various organs and species.
PMID- 9634604
TI - Immunocytochemistry and in situ hybridization studies of pepsinogen C-producing
cells in developing rat fundic glands.
AB - The ontogeny of pepsinogen C-producing cells in rat fundic glands was studied by
means of light and electron microscopy using an antiserum raised against a
synthetic peptide based on rat pepsinogen C. To confirm the immunocytochemistry
results, the expression of rat pepsinogen C messenger RNA (mRNA) in the fundic
gland was also examined by in situ hybridization using a digoxigenin-labeled RNA
probe. In adult rats, pepsinogen C was produced by chief cells, mucous neck
cells, and intermediate mucopeptic cells. Pepsinogen C-producing cells appeared
in embryos as early as 18.5 days' gestation. The development of these cells could
be classified into four stages: (1) 18.5 days' gestation to 0.5 days after birth;
(2) 0.5 days to 2 weeks after birth; (3) 3-4 weeks after birth; (4) 4-8 weeks
after birth. In embryos and young animals, pepsinogen C-producing cells were
mucopeptic cells. By 4 weeks after birth, mucous neck cells could be
distinguished morphologically. The maturation stages of the chief cells could be
traced by electron microscopy along the longitudinal axis of the rat fundic gland
by double-staining with anti-pepsinogen C antibody and periodic acid
thiocarbohydrazide-silver proteinate. Positive reactions for pepsinogen C and
pepsinogen C mRNA expression were detected in mucous neck cells. Therefore, we
conclude that mucous neck cells are precursor cells of chief cells. Mucous neck
cells, intermediate cells, and chief cells are in the same differentiating cell
lineage.
PMID- 9634605
TI - Methodological aspects of assessing phagocytosis of Vibrio anguillarum by
leucocytes of gilthead seabream (Sparus aurata L.) by flow cytometry and electron
microscopy.
AB - In this paper we optimize a flow cytometric method for evaluating the phagocytic
activity of leucocytes in gilthead seabream (Sparus aurata L.) and characterize
the phagocytic cells observed. Optimal conditions were established for the
fluorescein-labelling and analysis of the bacterium Vibrio anguillarum by flow
cytometry. Head-kidney leucocytes were incubated with the heat-killed fluorescein
isothiocyanate (FITC)-labelled bacteria for different periods, during which the
kinetics of phagocytosis was studied. Attached and interiorized bacteria were
distinguished. Although phagocytic ability reached a maximum after 60 min,
phagocytic capacity reached its maximum at 20 min. The amount of ingested
bacteria per phagocyte was estimated from the mean fluorescence of the
leucocytes. Cytochalasin B or colchicine was used to inhibit phagocytosis.
Monocyte-macrophages and acidophilic granulocytes showed phagocytic activity as
demonstrated by transmission electron microscopy. In conclusion, the technique
presented allows the screening of thousands of cells, and individual cell
evaluation, by quantifying interiorized particles in fish phagocytes. Our
ultrastructural results demonstrate that V. anguillarum is actively phagocytized
by seabream macrophages and acidophilic granulocytes.
PMID- 9634606
TI - Special smooth muscle cells along the submucosal surface of the guinea pig colon
with reference to its spontaneous contractions.
AB - Antiperistalses occur from the flexure region of the guinea pig colon. We
previously demonstrated that the circular muscle at the mesenteric border of the
flexure region produced spontaneous regular contractions and found special smooth
muscle cells believed to be pacemakers along the submucosal surface of the
circular muscle layer. In this study, we revealed bipolar- and multipolar-type
special smooth muscle cells along the submucosal surface of the muscle layer.
Their slender cell processes contacted each other and formed a cellular network.
Caveolae, filament structures expressing smooth muscle actin, vimentin, some
desmin, and basal lamina were prominent features. The special smooth muscle cells
corresponded to c-Kit-immunopositive cells and so-called interstitial cells or
interstitial cells of Cajal in other reports. Their population was larger in the
flexure region and the proximal colon than in the distal colon. The circular
muscle layer at the flexure region was thicker than in other regions. The
contraction in the flexure region showed the highest frequency and regularity.
The dense population of special smooth muscle cells at the flexure region and
thicker muscle layer may make the mechanical contraction more regular. The
antiperistalsis from the flexure region could be explained in relation to the
highest frequency of the pulsating contraction.
PMID- 9634607
TI - Corpuscles of Stannius and stanniocalcin-like immunoreactivity in the white
sucker (Catostomus commersoni): evidence for a new cell-type.
AB - The distribution of stanniocalcin immunoreactivity was examined in the corpuscles
of Stannius of the white sucker (Catostomus commersoni) by using a chum salmon
stanniocalcin antiserum, Western blotting, and light and electron microscopy. The
white sucker possesses at least two stanniocalcin-immunoreactive corpuscles in
the most posterior portions of the kidneys. Immunocytochemistry and
ultrastructure revealed two cell-types in the corpuscle parenchyma, only one of
which was immunoreactive. The nonimmunoreactive cells contained dense-cored
vesicles and long processes that extended between the immunoreactive cells and
terminated at perivascular spaces. When corpuscle extracts were subjected to
electrophoresis and Western blotting, three nonreduced stanniocalcin-like
immunoreactive bands (approximately 56, 61, and 64 kDa) were observed. However,
in the presence of a reductant, a diffuse band migrating in the range of 28 to 32
kDa was noted. The results of this study on the white sucker demonstrate the
presence of a dimeric stanniocalcin-like molecule and present evidence of a
previously uncharacterized cell-type in the corpuscles of Stannius.
PMID- 9634608
TI - Segmental muscle fiber lesions after repetitive eccentric contractions.
AB - Immunohistochemical and electron-microscopic techniques were used to analyze the
extensor digitorum longus muscles of New Zealand White rabbits 1 h, 1 day, 3, 7,
and 28 days after repetitive eccentric contractions. Loss of the cytoskeletal
protein desmin was the earliest manifestation of injury. Apart from 1 h post
exercise, all desmin-negative fibers stained positively with antibody to plasma
fibronectin, indicating loss of cellular integrity accompanying cytoskeletal
disruption. Fiber sizes were significantly increased from 1-7 days after
exercise. The large (hyaline) fibers found in histological sections after
repetitive eccentric contractions resulted from segmental hypercontraction of the
fiber. This phenomenon occurred proximally and distally to plasma membrane
lesions of the muscle fiber and necrosis and manifested itself as very short
sarcomere lengths. Thus, in serial sections, staining characteristics, sizes and
shapes of one and the same fiber often varied dramatically. We conclude that the
following sequence of events occurs: cytoskeletal disruptions, loss of
myofibrillar registry, i.e., Z-disk streaming and A-band disorganization, and
loss of cell integrity as manifested by intracellular plasma fibronectin stain,
hypercontracted regions, and invasion of cells. When a fiber is disrupted, the
remaining intact fibers apparently take up the tension put on the muscle and
later fewer fibers are subjected to eccentric contractions.
PMID- 9634609
TI - Ultrastructural and lanthanum tracer examination of rapidly resorbing rat
alveolar bone suggests that osteoclasts internalize dying bone cells.
AB - Glutaraldehyde-formaldehyde fixed undecalcified alveolar bone from 7-day-old rats
was prepared for light and electron microscopy. Colloidal lanthanum was used as
an ultrastructural tracer, and both random and semi-serial sections were
examined. Lanthanum penetrated the infoldings of the ruffled border and some
nearby vacuoles and vesicles. The majority of vacuoles and vesicles were
lanthanum-free. Some osteoclast profiles contained a large vacuole with a cell
enclosed in its interior. The enclosed cell exhibited an irregular nucleus
containing condensed peripheral chromatin, intact cytoplasmic organelles,
conspicuous rough endoplasmic reticulum and large blebs on the cell surface.
These features are characteristic of osteoblasts or bone-lining cells or immature
osteocytes which may be undergoing apoptosis or necrosis. The observation of
remnants of cellular structures within internalized osteoclast vacuoles, together
with the above results, suggests that osteoclasts engulf and probably degrade
dying osteoblasts/bone-lining cells or immature osteocytes.
PMID- 9634638
TI - Mechanisms regulating the binding activity of CD44 to hyaluronic acid.
AB - CD44 is a cell surface glycoprotein present on many cell types. Many CD44
isoforms have been identified. All CD44 isoforms utilize identical transmembrane
and cytoplasmic domains. The hematopoietic form of CD44 (CD44H) is the major CD44
protein present on normal human lymphocytes and monocytes. One of the ligands for
CD44 is hyaluronic acid (HA), a polymer consisting of repeat units of
disaccharide; N-acetyl-D-glucosamine and N-acetyl-D-glucuronic acid. Since HA is
present ubiquitously in extracellular matrix and in circulation, promiscuous
binding of HA to CD44 may have undesirable affect. Similar to other adhesion
molecules, binding of HA to cell surface CD44 requires regulation. In this
review, we summarized our studies using a human lymphoma cell line, Jurkat. We
found that binding of CD44+ Jurkat transfectants to HA requires cellular
activation. Cellular activation induces the reorganization of the cytoskeleton
proteins. Reorganization of cytoskeletal proteins results in clustering of CD44
on the cell surface. Clustering of CD44 on the cell surface is a prerequisite for
the homodimerization of CD44. Our studies on Jurkat transfectants and results
from other investigators suggest that interactions between CD44 and HA is a
dynamic process and requires the participation of different cellular components;
depending of the nature of the cell type and/or the nature of the activation
signals.
PMID- 9634639
TI - Adventitial gene transfer to arterial wall.
AB - Vascular gene transfer offers a promising alternative for the treatment of
cardiovascular diseases. Blood vessels are among the easiest targets for gene
therapy and in most conditions only a temporary expression of the transfected
gene will be required to achieve a beneficial biological effect. Adenoviruses
lead to most efficient transgene expression in arterial wall. Depending on the
treatment requirements, gene transfer to the artery wall can be accomplished both
from lumen and from adventitia. Promising therapeutic effects have been obtained
in animal models of restenosis with the transfer of vascular endothelial growth
factor (VEGF), nitric oxide synthase, thymidine kinase, retinoblastoma, growth
arrest homeobox gene and antisense oligonucleotides against transcription factors
or cell cycle regulatory proteins. First experiences of VEGF gene transfer to
human peripheral arteries have also been reported. However, further studies
regarding gene transfer techniques, vectors and safety of the procedures are
needed before a full therapeutic potential of gene therapy in vascular diseases
can be evaluated.
PMID- 9634640
TI - Anticholinergic action of clonidine in rats with sinoaortic denervation.
AB - A study was carried out relating to the anticholinergic action of clonidine on
the cardiovascular responses to i.c.v. injection of neostigmine, a quaternary
anticholinesterase, in conscious sham-operated animals and rats with sinoaortic
denervation, 7 days after the corresponding operation. Neostigmine (0.1-1
micrograms i.c.v.) induced a dose-dependent pressor and bradycardic responses in
sham-operated rats but induced only an increase in blood pressure in sinoaortic
denervated animals. However, the pressor response in sinoaortic-denervated rats
was significantly greater than in sham-operated animals. Clonidine (10 micrograms
kg-1 i.v.) induced a fall in mean arterial pressure in sinoaortic-denervated rats
but not in sham-operated animals. Moreover, sinoaortic denervation reduced the
bradycardic action of this antihypertensive drug. The anticholinesterase activity
of clonidine (10 micrograms kg-1 i.v.), given 30 min previously, prevented the
bradycardic action of neostigmine (0.1-1 micrograms i.c.v.) but failed to modify
the pressor effect in sham-operated rats. This alpha2-adrenergic agent reduced
the pressor response to i.c.v. administration of neostigmine in sinoaortic
denervated rats. Alternatively, the i.c.v. administration of clonidine (3
micrograms i.c.v.), given either 15 or 30 min before neostigmine, only prevented
the bradycardic effect of the anticholinesterase (0.3 micrograms i.c.v.) in sham
operated rats but not the pressor action of this drug. In sinoaortic denervated
rats, 3 micrograms of clonidine i.c.v. reduced an increase in blood pressure by
i.c.v. injection of the anticholinesterase. The results suggest different central
cholinergic mechanisms and different cholinergic-adrenergic interactions on the
cardiovascular responses elicited by centrally injected neostigmine in sinoaortic
denervated rats.
PMID- 9634641
TI - Screening of preformed oxidised low density lipoprotein isolated by a polyanion
precipitation method. Its correlation with serum triglyceride levels.
AB - For clinical and epidemiological screening a simple and sensitive methodology was
developed for detection of preformed lipid peroxides (LPO) in low density
lipoprotein (LDL). For this purpose, the iodometric assay of El-Saadani et al. (J
Lipid Res 1989;30:627-30) was adapted to the fraction containing LDL isolated by
polyanion precipitation avoiding ultracentrifugation. This fraction also includes
intermediate density lipoprotein. Stratifying 53 individuals by their serum
triglyceride levels (TG) the highest quartile showed a highly significant
elevation of LDL-LPO compared with the lowest one (69.2 +/- 41.2 vs 22.9 +/- 10.0
nmol mg-1 LDL-apo B, P < 0.001). LDL-LPO concentration also showed a strong
correlation with TG (r = 0.73, P < 0.00001) and significant inverse correlations
with high density lipoprotein cholesterol (HDL-C) and HDL3-C subfraction (r =
0.37, P < 0.01 and r = -0.38, P = 0.01, respectively). The TG/HDL-C ratio, which
is closely associated with insulin resistance, was strongly correlated with LDL
LPO (r = 0.83, P < 0.00001). Significant elevations of LPO were observed in
phenotypic hyperlipoproteinemias (HLP) IIb and IV (P < 0.01 and P < 0.02,
respectively) and when expressing LPO in mol/mol of LDL-apo B, two- and 2.5-fold
higher values were found in types IIb and IV HLP, respectively, compared with
normolipidemic subjects, suggesting a more oxidative environment for apo B in
both phenotypes. No variations in LPO were found in type IIa HLP. This simple
assay for in vivo detection of LDL-LPO, emphasises the possible atherogenic
effect of TG through their oxidative capacity and suggests the integration of LPO
to the cluster of associated risk factors: high TG, low HDL-C and insulin
resistance.
PMID- 9634642
TI - Different aspects of the effects of thapsigargin on automatism, contractility and
responsiveness to phenylephrine in cardiac preparations from rats and guinea
pigs.
AB - Sarcoplasmic reticulum (SR) Ca(2+)-ATPase play a very important role in
excitation-contraction coupling in the heart. The effects of thapsigargin (TG), a
selective inhibitor of SR Ca(2+)-ATPase in the heart muscle, on automatism and
contractility of the rat and guinea pig heart were examined. Experiments were
performed on isolated right auricula and right ventricle papillary muscle. The
following parameters were registered: force of contraction (Fc); rate of rise of
force (+dF/dt); rate of fall of force (-dF/dt); time to peak contraction (ttp);
duration of relaxation phase of contraction at the level of 10% of total
amplitude (tt10); and automatism (b.p.m.). Additionally, the influence of
thapsigargin on the effects of phenylephrine on the above mentioned parameters
were studied. It was found that TG (1 microM) decreased only the automatism in
rat heart, but increased automatism and ttp duration and decreased Fc in guinea
pig heart. The positive force-frequency relation in the guinea pig heart was
attenuated. The effects of phenylephrine in the rat heart were not significantly
different before and after pretreatment with TG. Alternatively, pretreatment with
TG exerted a profound influence on the effects of phenylephrine in the guinea pig
heart. The results indicate that TG has different effects on the guinea pig and
rat hearts. The reason for this could be due to species differences, i.e. the
weaker crossing of TG through the membrane of rat myocytes or a different
mechanism of Ca2+ homeostasis in rat and guinea pig hearts.
PMID- 9634643
TI - Gastric cytoprotective activity of dehydroleucodine in rats. Role of nitric
oxide.
AB - Previously we reported that dehydroleucodine (DhL), a sesquiterpene lactone,
shows gastric and duodenal cytoprotective activity. The mechanism is not mediated
by antiacid secretory action; DhL stimulated mucus production and indomethacin
pretreatment reduced cytoprotective action. In the present study we demonstrated
that the gastric cytoprotective effect is antagonized by the nitric oxide (NO)
synthase inhibitor, NG-nitro-L-arginine. The inhibitory action of NG-nitro-L
arginine is reversed by L-arginine, but not D-arginine. The findings suggest that
NO is involved in the gastroprotection induced by DhL.
PMID- 9634644
TI - Experimental approaches for observing homologous desensitisation and their
pitfalls.
AB - Whereas molecular mechanisms of cell desensitisation have been discussed at
length in the literature, little organised information on the methods for
studying desensitisation of cellular responses has been published. In this
article, three commonly utilised protocols for studying homologous
desensitisation of cellular responses are evaluated. These are (1) observation of
attenuation of a response after an initial stimulus-induced activation, (2)
repeated stimulation of cells after washing away the previous stimulus, and (3)
repeated stimulation without a wash step. Advantages and limitations of each
protocol are discussed and data is presented demonstrating some of the properties
of the protocols.
PMID- 9634645
TI - Inhibition of wound-induced expression of transforming growth factor-beta 1 mRNA
by its antisense oligonucleotides.
AB - Transforming growth factor-beta 1 (TGF-beta 1) is a member of a gene superfamily
that regulates proliferation, differentiation and other functions in many cell
types. To gain insight into the role of TGF-beta 1 in wound repair, we have
analysed the ability of an antisense TGF-beta 1 oligodeoxynucleotides (ODN) to
specifically inhibit wound-induced expression of TGF-beta 1 mRNA in the mouse
skin. Although injury induced the expression of TGF-beta 1 mRNA at the wound
sites, expression of TGF-beta 2-or TGF-beta 3-mRNA was not detected. In
comparison to the 24 h following injury, higher levels of TGF-beta 1 mRNA
expression were observed in the wound sites after 72 h. Northern blotting and in
situ hybridisation analysis showed that wound sites treated with antisense TGF
beta 1 ODN exhibited no detectable levels of TGF-beta 1 mRNA after injury,
whereas the sites treated with sense TGF-beta 1 ODN possessed significant amounts
of its mRNA. Our results demonstrated that antisense TGF-beta 1 ODN inhibited the
wound-induced expression of TGF-beta 1 mRNA in vivo.
PMID- 9634646
TI - Tolerance develops to the antinociceptive and motor impairing effects of ACEA
1416, a NMDA receptor antagonist, in the formalin and rotarod test in mice.
AB - Antinociception, disturbances of motor coordination and development of tolerance
to these effects were examined following acute and chronic administration of ACEA
1416, a NMDA receptor/glycine site antagonist, in Swiss Webster mice using the
formalin and rotarod tests. In the formalin test, mice were injected with either
the vehicle (Tris, 0.05 M) or ACEA-1416 (1-10 mg kg-1). Fifteen or 60 min later,
mice were injected with formalin and observed for nociceptive responses (licking
and/or biting of the injected paw). In the vehicle-treated control mice a
biphasic nociceptive response was observed at 0-5 min (early phase) and from 15
to 50 min (late phase) after formalin injections. ACEA-1416 showed a dose
dependent attenuation of the nociceptive responses in both phases of the formalin
test. In the rotarod test, mice were injected with ACEA-1416, placed on a
rotating bar at 6 rpm for 2 min and examined for motor impairments. ACEA-1416
produced disturbances of motor coordination in a dose-dependent manner. For
tolerance studies, mice were injected once daily with either the vehicle or ACEA
1416 (30 mg kg-1) and tested for antinociception and motor impairment on day 5,
10 and 20. A time-dependent decrease in the antinociceptive effect of the drug
was observed in the early but not in the late phase of the formalin test.
Tolerance also developed to the motor impairing effect of the drug. Taken
together, these data suggest that chronic inhibition of NMDA receptors by ACEA
1416 differentially affected the antinociceptive effect of the drug in the early
and late phase of the formalin test. Furthermore, the antinociceptive and motor
impairing effects of the drug can be separated.
PMID- 9634647
TI - Taste conditioning effects of buprenorphine in morphine-naive and morphine
experienced rats.
AB - Male Sprague-Dawley rats were injected daily with saline (morphine-naive rats) or
20 mg kg-1 morphine (morphine-experienced rats), starting 15 days before the
experiment. Subsequent taste conditioning indicated that 0.1 mg kg-1
buprenorphine significantly decreased 0.025% saccharin consumption in morphine
naive, but not in morphine-experienced rats. A 10 mg kg-1 dose of morphine gave
similar results, while d-amphetamine (0.75 mg kg-1) was consistently aversive. It
was concluded that morphine experience selectively blocks the aversive effects of
buprenorphine in rats; thus it possibly increases the potential for buprenorphine
abuse.
PMID- 9634648
TI - Dose-dependent pancreatotrophic effect of cholecystokinin-octapeptide in the rat:
the influence of starvation.
AB - Cholecystokinin (CCK) and its analogues are known to exert trophic effects on the
exocrine pancreas, whereas at high doses, they produce pancreatic injury. This
study was carried out to study the effect of starvation on the dose-dependent
pancreatotrophic effect of CCK-8 in rats. Normal or fasted rats were treated with
CCK-8 doses ranging from 0.5 to 32 and 0.5 to 8 micrograms kg-1, respectively,
twice daily for 5 days. Pancreatic size, protein, DNA, secretory enzyme and
trypsin inhibitor (PSTI) contents as well as histology were examined. In normal
rats, CCK-8 increased the pancreatic content of protein, amylase, serine
proteases and PSTI with maximum values between doses of 2 and 16 micrograms kg-1.
The dose of 32 micrograms kg-1, however, yielded less trophic responses. Given to
fasted rats, CCK-8 increased the weight as well as protein and secretory enzyme
contents of the pancreas with maximum values between doses of 1 and 4 micrograms
kg-1. The first dose supramaximum for the trophic responses was as low as 8
micrograms kg-1. Histology revealed necroinflammatory damage (acinar cell
vacuolization, focal cell necrosis) in the exocrine pancreas at supramaximum
doses of CCK-8 in both groups. Cell necroses and vacuolization were less but
present even at doses optimum for trophism and exhibited dependence on both the
dose of CCK-8 and nutrition. In either the normal or fasted animals, the
periinsular acini were relatively less affected by the toxic effects of CCK-8
than the teleinsular ones. The results indicate that starvation makes the
exocrine pancreas more sensitive to necroinflammatory effects of CCK-8. The
relative protection seen in periinsular acini suggests a modulatory influence of
islet hormones on development of CCK-induced acinar cell injury.
PMID- 9634649
TI - Swiss regulations for controlling clinical trials.
AB - Switzerland has recently issued regulations designed to control all trials with
drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per
il controllo dei medicamenti in fase di studio clinico' (Intercantonal
Regulations Controlling Drugs used in Clinical Trials), which have been operating
since 1st January 1995. These new regulations are generally consistent with other
international regulations and have introduced the concept of good clinical
practice (GCP) into Switzerland. There are other regulations in Switzerland, such
as Federal regulations on immunobiological products, special rules governing the
administration of radiolabelled drugs to humans, drugs of abuse and medical
devices. Any gap in the central regulations must be filled by cantonal
regulations, where they exist. This is a comprehensive review of the regulations
governing clinical trials in Switzerland, with special attention being devoted to
trials with therapeutic compounds and to compatibility between Swiss and
international procedures.
PMID- 9634650
TI - Protein identification in the post-genome era: the rapid rise of proteomics.
PMID- 9634651
TI - From membrane to molecule to the third amino acid from the left with a membrane
transport protein.
AB - The lac permease of E. coli is a paradigm for secondary active transporter
proteins that transduce the free energy stored in electrochemical ion gradients
into work in the form of a concentration gradient. This hydrophobic, polytopic,
cytoplasmic membrane protein catalyses the coupled, stoichiometric translocation
of beta-galactosides and H+, and it has been solubilized, purified, reconstituted
into artificial phospholipid vesicles and shown to be solely responsible
responsible for beta-galactoside transport as a monomer. The lacY gene which
encodes the permease has been cloned and sequenced, and all available evidence
indicates that the protein has 12 transmembrane domains in alpha-helical
configuration that traverse the membrane in zigzag fashion connected by
hydrophilic loops with the N and C termini on the cytoplasmic face of the
membrane. Extensive use of site-directed and Cys-scanning mutagenesis indicates
that very few residues in the permease are directly involved in the transport
mechanism, but the permease appears to be a highly flexible protein that
undergoes widespread conformational changes during turnover. Based on a variety
of site-directed approaches which include second-site suppressor analysis and
site-directed mutagenesis, excimer fluorescence, engineered divalent metal
binding sites, chemical cleavage, EPR, thiol crosslinking and identification of
discontinuous mAb epitopes, a helix packing model has been formulated.A mechanism
for the coupled translocate ion of substrate and H+ by the lac permease of E.
coli is proposed. Four residues are irreplaceable with respect to coupling, and
the residues are paired in the tertiary structure--Arg-302 (helix IX) with Glu
325 (helix 10) and His-322 (helix 10) with Glu-269 (helix VIII). In an adjacent
region of the molecule at the interface between helices VIII and V is the
substrate translocation pathway in which Glu-126 and Arg-144 appear to play key
roles. Because of this arrangement, interfacial changes between helices VIII and
V are transmitted to the interface between helices IX and X and vice versa. Upon
ligand binding, a structural change at the interface between helices V and VIII
disrupts the interaction between Glu-269 and His-322, Glu-269 displaces Glu-325
from Ag-302 and Glu-325 is protonated.Simultaneously, protonated Glu-325 becomes
inaccessible to water which drastically increases its pKa. In this configuration,
the permease undergoes a freely reversible conformational change that corresponds
to translocation of the ternary complex. In order to return to ground state after
release of substrate, the Arg-302-Glu-325 interaction must be reestablished which
necessitates loss of H+ from Glu-325. The H+ is released into a water-filled
crevice between helices IX and X which becomes transiently accessible to both
sides of the membrane due to a change in helix tilt, where it is acted upon
equally by either the membrane potential or the pH gradient across the membrane.
Remarkably few amino-acid residues appear to be critically involved in the
transport mechanism of lac permease, suggesting that relatively simple chemistry
drives the mechanism. On the other hand, widespread, cooperative conformational
changes appear to be involved in turnover. As a whole the data suggest that the
12 helices which comprise the permease are loosely packed with a considerable
amount of water in the interstices and that surface contours are important for
sliding or tilting motions that occur during turnover. This surmise coupled with
the indication that few residues are essential to the mechanism is encouraging in
that it suggest that the possibility that a relatively low resolution structure
(i.e. helix packing) plus localization of the critical residues and the
translocation pathway can provide important insights into the mechanism.
(ABSTRACT TRUNCATED)
PMID- 9634652
TI - Infrared spectroscopy of proteins and peptides in lipid bilayers.
PMID- 9634653
TI - [Obtention and characterization of murine beta-NGF. Application in a model of
cerebral aging].
AB - INTRODUCTION: beta-NGF is a basic protein of 118 aminoacids which acts are a
trophic factor for sensory and sympathetic neurons of the peripheral nervous
system, and on cholinergic neurons of the anterior basal cerebrum. OBJECTIVES: In
view of the functional effect of beta-HGF and its possibilities as a therapeutic
agent in neurodegenerative disease, including Alzheimer's disease in this study
our aim was to obtain, characterize and show the main results of the application
of beta-NGFm in a model of cerebral ageing in rats with cognitive disorders.
MATERIAL AND METHODS: For the obtention of beta-NGFm we followed Mobley's method
as modified by Ebendal and used mouse submaxillary gland as a source of raw
material. The characterization studies were carried out by application of seven
techniques which allowed physicochemical characterization and demonstration of
the biological activity of the product. Application of beta-NGF obtained under
these conditions was carried out in a mode of cerebral ageing and the effects of
treatment were assessed by conduct studies, measurement of the activity of the
enzyme acetyl cholinesterase and study of neural plasticity. CONCLUSIONS:
Characterization studies carried out on the beta-NGFm showed that the protein
obtained consists of a mixture of molecules of beta-NGFm which are intact at
their extreme N-Terminal, and molecules which have lost the octapeptide of the N
terminal position and show some modification increasing hydrophobicity. All these
species were recognized immunologically by the specific antibody anti-NGFm and
showed biological activity.
PMID- 9634654
TI - [Clinical characterization of patients with multiple sclerosis defined in Cuba].
AB - INTRODUCTION: Since 1975 no studies have been done in Cuba defining the clinical
characteristics of patients with multiple sclerosis (MS). OBJECTIVE: To describe
the characteristics of a group of Cuban patients with definite clinical MS.
MATERIAL AND METHODS: Fifty eight patients with definite clinical MS were studied
(Poser et al) with normal motor (VCM) and sensory (VCS) conduction velocities.
Tests were done on them: clinical scale (Scripps), incapacity (EDSS) and quality
of life (Steps), together with various complementary tests. Each patient was
classified according to the way in which the disease evolved. Also the two
commonest clinical types were compared and we applied the difference test between
percentages of non-paired samples with an alfa level of 0.05. RESULTS: Onset of
the illness in most cases was before the age of 40 (86.1%), 75.9% were women and
82.8% were white. In 15.3% there was a family history of MS. In 25.9% there were
psychiatric disorders and trigger factors (43.1%. The most frequent initial
symptoms were pyramidal (48.3%) sensorial (41.4%) and cerebellar (39.7%). Scripps
scale scores were < 80 in 60.2%, in EDSS < 5 (61.9%) and in the Clinical Steps <
3 in 65.4%). Motor potentials (81.9%) somatosensory potential (PESS) (72.3%) and
magnetic resonance imaging (MR) (76.4%) were the most abnormal results.
Exacerbation-remission (ER) was the most frequent type of evolution (53.4%)
generally affecting patients aged under 40 years old (p = 0.02), EDSS < 5
(64.4%), Scripps > 80 (61.2%), Steps < 3 (95.6%), pyramidal system involvement
(58.5%), cerebellar (29.2%) and MRI abnormality (80%). The progressive primary
form (PP) was the second most frequent (29.3%); 29.4% were under 40 years of age,
had more marked changes in all functional system (100%), degree of incapacity and
quality of life (100%). PESS (92.5%); the urodynamic tests 58.85%) were less
positive on MRI (54.5%) as compared with the ER form. CONCLUSIONS: The
differences found between the clinical forms ER and II indicate that there is
greater deterioration in the PP form, probably due to age and more cerebellar and
spinal cord involvement.
PMID- 9634655
TI - [Deficiency, disability and handicap in multiple sclerosis: a population-based
study in Valladolid].
AB - INTRODUCTION: Apart from impairment there is hardly any other assessment of the
repercussions of multiple sclerosis (MS) in population studies. OBJECTIVE: To
analyze the functional state of en epidemiological series of patients in the
Valladolid health district. MATERIAL AND METHODS: A descriptive transversal study
of a geographically defined population base. During a period of three months and
complementing a prevalence study, were assessed, by means of the Minimal Record
of Disability, impairment, disability and handicap in a series of 51 patients (33
women and 18 men) with clinically defined MS, who lived in the area on 1 March
1997. RESULTS: There was a primarily progressive evolution in 21.6% of the
patients, and secondarily progressive in 11.8%. Average follow-up time was 9.1
years (range 1-41) and average age of onset 27.8 years (range 14.7-51.0). The
distribution of scores on the Expanded Disability Status Scale was bimodal
(average and interquartile range: 3.0 (1.5-5.0). 80.4% of the patients continued
to be ambulatory. 21.5% had frequent urinary incontinence or required a long-term
urinary catheter. Less than 20% needed help with day to day activities. 78% of
the patients complained of some degree of fatigue, and 51% had difficulties with
social relationships. 59.4% of the patients had full-time jobs and 70.6% had no
financial problems. CONCLUSIONS: The study shows that the functional state of
persons with MS is better than was thought, and that assessment of the
consequences of this illness should include disability and handicap profiles.
PMID- 9634656
TI - [Follow-up of partial seizure progression in an infant].
AB - OBJECTIVE AND MATERIAL: We are carried out a retrospective study of 43 patients,
21 males and 22 women entered during the period of infancy in the Service of
Neurology of our hospital and with diagnostic of any type of partial seizure, in
an intent to correlate a series of clinical parameters, electroneurophysiologics
and initial therapeutics with their factors follow-up periods. RESULTS: They are
a half age of 7.11 months (1-19), consecutive being controlled for a period of
time of 40 months (6-96). We have settled down a relationship between the drugs
utilized in the first seizure and that other that they remained in their last
revision, the current state of the critical manifestations, and the existence or
not of an agreement between the e diagnosis emitted to the discharge and the
development of the illness. CONCLUSION: After the present study, we thought that
the current classification of the epileptic seizures is insufficient in the age
of the infant, with presages much more complexes.
PMID- 9634657
TI - [Comparison of the multifactorial model as a hereditary mechanism of non
myoclonic generalized idiopathic epilepsy and partial idiopathic epilepsy].
AB - OBJECTIVE AND METHODS: An experimental study about the predictions from the
multifactorial threshold model created by Falconer is presented, assuming that
this model may explain the genetic mechanisms underlying the family aggregation
of idiopathic epilepsies. RESULTS: We failed to confirm the following predictions
from the falconer model: decreased prevalence of disease in relatives,
proportional to decreased family links, and the order of birth effect. An
heredity greater than 100% was calculated which is concordant with the presence
of at least a locus with a major gen affect. CONCLUSION: Our results reject the
multifactorial threshold effect and suggest the presence of a major gen or
Mendelian effect. An analysis of complex segregation is suggested for future
studies.
PMID- 9634658
TI - [Nerve growth factor and neurological diseases].
AB - INTRODUCTION: The effects of Nerve Growth Factor (NGF) within and outside the
nervous system have been amply discussed in recent decades. Recently clinical
studies have shown the effectiveness of this growth factor in the treatment of
neurodegenerative disorders. This clinical use makes it necessary to have
sensitive, specific methods available to permit measurement of the level of this
protein and to determine how it behaves during the course of treatment.
OBJECTIVE: To describe the measurement of NGF levels in human serum using an
immunoenzymatic method and evaluating the levels of this protein in some
neurological disorders. Materials and methods. NGF levels were measured in the
serum of healthy persons and in patients with Alzheimer's disease (AD)
Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis
(MS) and Huntington's chorea (HC) using a double site immune-enzymatic assay.
Murine 27/21 anti-beta-NGF monoclonal antibody was used as the antibody to cover
the plate and as conjugate. RESULTS: Adding a block pass to the method, in which
the sample was incubated with an excess of 27/21 antibody effectively reduced the
signal observed in the immuno-enzymatic assay. A moderate reduction in beta-NGF
levels was seen in the serum of patients with ALS and MS. There was a
statistically significant reduction in the patients who were carriers of PD and
HC. CONCLUSIONS: The significant reduction in NGF levels in patients with PD and
HC may be associated with a disorder in the use of this protein in central and
peripheral tissues.
PMID- 9634659
TI - [Cerebral venous thrombosis in the region of Murcia].
AB - INTRODUCTION AND OBJECTIVE: Massive usage of new neuroimaging techniques has
produced an increase in the number of patients with cerebral venous thrombosis.
Our aim has been to evaluate this shift in our county through the clinico
radiologic characteristics of the patients admitted to our unit. MATERIAL AND
METHODS: Over the last 7 years a total of 12 patients suffering from cerebral
venous thrombosis were attended in our department. We have analyzed
retrospectively their clinical records. RESULTS: There were 11 women 1 man with a
range of ages from 13 to 60 years old. The main associated factor was oral
contraceptives intake. Most of them presented with symptoms of benign
intracranial hypertension. Magnetic resonance imaging was the most sensitive
diagnostic tool. Outcome was good in general. Most of them were treated with
intravenous heparin during the acute phase and received oral anticoagulation for
6 months. More than half were diagnosed all over the last three years.
CONCLUSIONS: Our data seem to confirm this tendency towards a larger number of
cases with the application of new diagnostic tools. In these cases, clinical
course is more benign than reported in classical series.
PMID- 9634660
TI - [Neonatal sciatic palsy: etiology and outcome of 21 cases].
AB - INTRODUCTION: Sciatic nerve paralysis is a rare entity in the newborn. Few
reference in specialized tests indicate that in the majority of cases the sciatic
palsy has been observed after misplaced injections into the buttocks. The
prognosis is variable and appears to be better after umbilical vessel
catheterization for injection of medications than after misplaced muscular
injections. In case of recovery it takes place within 3 to 12 months. OBJECTIVE:
The objective of the present study is to know the evolution of neonatal sciatic
palsy and to determine their injury noxe in regard to perinatal factors, and
their relationship with long-time outcome, and to look for prognostic clues of
clinical utility. MATERIAL AND METHODS: We evaluated perinatal factors of newborn
children with sciatic nerve paralysis, followed for more than 18 months of
clinical evolution, in a neuropediatric centre. RESULTS: Twenty one newborn with
such criteria were evaluated. Gestational age was within 32 and 42 weeks (median
38.2). The birth weight was between 2,100 and 4,100 g (median 2,973). The
majority of cases obtained total recovery (16 of 21). The time of recovery was 4
to 14 months (median 8.8). Free ambulation was obtained by all cases (at 10 to 24
months). No apparent cause was observed in the majority of cases. Cesarean
delivery was more frequent specially in cases with permanent consequences.
CONCLUSION: Long-time prognostic of neonatal sciatic palsy is generally good. In
our series all the cases with consequences were associated to cesarean delivery.
The duration of cesarean intervention and the anesthesic hypotony of the newborn
could be implicated in the sciatic nerve injury of poor outcome.
PMID- 9634661
TI - [Tables of normal values of average and long latency auditory potentials].
AB - INTRODUCTION AND OBJECTIVE: In view of the disparity of data and methodology
concerning medium (MAEP) and long latency (LAEP) acoustic evoked potentials, we
have obtained tables of normal values using a reliable method and statistical
study of these potentials in 30 healthy persons, in order to serve as a basis for
clinical reference and for possible further studies. MATERIAL AND METHODS: In the
MAEP we used the two types of stimuli most commonly employed, first a click and
then a rising-plateau-falling tone (2-6-2). We observed that this did not affect
the latency or amplitude of the different waves, although the best defined waves
are obtained with tones. In the LAEP we always used a tone with rise-plateau-fall
of 10-50-10, as recommended by the American Electroneurophysiological Society. In
all cases the intensity was of 70 db, with rarefaction and masking of the
contralateral ear with an intensity of 50 db. Self-adhesive electrodes were used
for captation; the active one was placed on the ipsilateral ear lobe and the
reference electrode in Cz for the LAEP. For the LAEP the lower filter was of 1 Hz
and the higher of 70 Hz. In view of the variety of filters recommended, 10 Hz at
the lower level and 500, 1000 and 2000 at the higher level were used successively
for the MAEP. We observed that these did not affect the latency or amplitude of
the waves, so these three values may all be used equally well. RESULTS AND
CONCLUSIONS: In the inter-sexual study, no differences were seen between men and
women. Nor were there significant differences between the acoustic evoked
potentials on the right and left sides of the same person.
PMID- 9634663
TI - [Giant intraventricular arachnoid cyst: report of 2 cases].
AB - INTRODUCTION: It is very unusual to find cysts situated intraventricularly. Only
24 cases have been described to date in the literature. CLINICAL CASES: In this
paper we present two new cases considering that because of their exceptional size
they deserve to be called 'giant'. The two patients had been diagnosed as having
epilepsy during childhood or youth. No neuroradiological studies had ever been
done. The cause of hospital admission in the first case was headache and vomiting
and in the second case a convulsive crisis. We did cerebral CT scans in both
cases and a MR control scan in the second case. This formed the basis for our
diagnosis. Unlike previous cases they were not operated on. Their clinical course
may be considered satisfactory to date, since there have been no further
convulsive crisis nor other neurological alterations. We have therefore been
conservative with regard to the indication for surgery in these patients.
CONCLUSIONS: Review of the literature does not completely clarify the origin of
these lesions but we are inclined to believe that there is an intimate
relationship between the formation of an intraventricular arachnoid cyst and the
choroid plexus. Many new cases will have to be diagnosed before we can fully
understand the true physiopathology of these cysts.
PMID- 9634662
TI - [Diagnosis in severe myoclonic epilepsy in childhood: study of 13 cases].
AB - OBJECTIVE: The purpose of this report is to describe clinical pattern, EEG,
outcome and differential diagnosis in severe myoclonic epilepsy in infancy
(SMEI). MATERIAL AND METHODS: We report 13 cases initially diagnosed of SMEI and
selected according to the following criteria: first seizure between 1 and 12
months of life, frequent seizures resistant to antiepileptic drugs, no previous
personal history of disease, normal psychomotor development before the first
seizure and normal EEG, CT scanning and laboratory analyses at the beginning. CT
and/or MRI were performed in 13 cases, arteriography in 2 patients, MR
spectroscopic imaging in 1 child and SPECT in 3 cases. Quantification of
enzymatic activities of the mitochondrial respiratory chain was made in 5
patients. RESULTS: Only 8 cases were finally diagnosed of SMEI according to ILAE
definition. In two cases, seizures were finally controlled with antiepileptic
treatment and EEG abnormalities disappeared. Three patients showed other
findings: mesiotemporal sclerosis, angiitis diffusely involving CNS and
mitochondrial cytopathy with deficiency of the complex IV. CONCLUSIONS: Although
diagnosis of SMEI, based on clinical manifestations, is suspected in most cases
from the first year of life, final diagnosis should not be confirmed until steady
state, when polymorphous seizures occur. Even then, differential diagnosis should
be made with other disorders. Perhaps, further studies should be performed in
order to identify and eliminate another etiology.
PMID- 9634664
TI - [Usefulness of the EEG recording in the diagnosis of cyclosporin A-induced
encephalopathy].
AB - INTRODUCTION: Cyclosporine A is one of the immunosuppressors most frequently used
to prevent transplant rejection. Neurotoxicity is one of the complications often
associated with it. These complications include acute encephalopathy, lethargy,
confusion state, tremor, headache, motor disorders, visual changes and epileptic
crises amongst others, even when blood levels are at what are considered to be
'therapeutic' levels. CLINICAL CASES: We present the EEG anomalies found in 3
transplant patients (two liver transplants and on double lung transplant) to whom
cyclosporin A had been given and who presented with status epilepticus. The EEG
recordings showed paroxystic discharges of focal onset in the temporo-occipital
areas. They were mainly correlated with the clinical findings of oculomotor and
eyelid disorders. CONCLUSION: The topography of the neurophysiological findings
supports--as do the other clinico-radiological findings--localization preferably
to the posterior areas of cerebral dysfunction associated with cyclosporin A.
Although the physiopathological origin of the encephalopathy of patients treated
with cyclosporin A seems to correspond to multiple factors, we wish to point out
the diagnostic usefulness of the identification of EEG changes localized to the
temporo-occipital areas in the recognition of the neurotoxic syndrome in these
patients.
PMID- 9634665
TI - [Neurocutaneous melanosis].
AB - INTRODUCTION: Neurocutaneous melanosis is an infrequent condition characterized
by the presence of numerous gigantic cutaneous naevi and melanocytic infiltration
of the central nervous system and/or the leptomeningeal layers. Different
clinical features may be seen: endocranial hypertension due to hydrocephalus,
cranial nerve paralysis, myelopathy, convulsive seizures, etc. The prognosis is
considered to be malignant. Only positive CNS histological findings confirm the
diagnosis. CLINICAL CASE: We present the case of a man with cutaneous lesions
compatible with the diagnosis of neurocutaneous melanosis since birth, with
benign self-limiting epilepsy in early childhood. Cerebral CT and MR scans were
normal until the age of 17, when hipper-signal lesions appeared on MR,
infiltrating the leptomeninges of the deep temporal pole and anterior aspect of
the cerebral peduncles, which suggested the presence of melanocytes in the CNS.
CONCLUSIONS: There are cases of neurocutaneous melanosis with a good medium-term
prognosis and benign manifestations until infiltration of the CNS occurs. Then
they start to show the classical behavior of cases with a malignant prognosis. MR
should be included as part of the diagnostic criteria for neurocutaneous
melanosis. MR should be done periodically in patients with cutaneous lesions
suggestive of this condition.
PMID- 9634666
TI - [Munchausen syndrome by proxy: report of one case with epilepsy].
AB - INTRODUCTION: Munchausen syndrome by proxy (MSBP) is a rare form of child abuse
in which a parent, usually the mother, fabricates or produces illness in a child,
so causing them unnecessary medical investigations, treatments and
hospitalizations. One of the commonest false presenting symptom is 'seizures'.
CLINICAL CASE: An eight years old boy with Munchausen syndrome by proxy is
reported. This child had had genuine seizures well controlled by standard
anticonvulsant treatment at the start of the false illness. At the age of seven
years, the patient showed very frequent seizures. The child was treated with
antiepileptic drugs, but treatments were ineffective and seizures continued.
Results of multiple tests, including an extensive blood chemistry analyses, CT,
MRI, SPECT, were normal. Electroencephalogram showed posterior slow waves. Acute
neurological deterioration was observed six weeks after hospitalization and it
was finally proved that seizures were caused or triggered by clomipramine
poisoning given by her mother. CONCLUSIONS: MSBP frequently presents as epileptic
seizures in these abused children. MSBP diagnosis is more difficult to be made if
true seizures exists with multiple fictitious seizures. Pediatrician should be
alerted to the possibility of MSBP when seizures are poorly controlled,
treatments are ineffective and there is no neurophysiologic dysfunction. Early
diagnosis and intervention are essential because high mortality and psychologic
morbidity are associated with this syndrome.
PMID- 9634667
TI - [Neuroimaging of hypoglycemia].
AB - INTRODUCTION: Sustained hypoglycemia causes serious cerebral damage. The cortex,
hippocampus and basal ganglia are particularly vulnerable to this. Exceptionally,
there have been communications regarding neuroimaging visualization of cerebral
lesions attributable to hypoglycemia only. We present the case of a woman who
suffered hypoglycemic coma with permanent neurological damage. Lesions were seen
on magnetic resonance (MR) and cranial computerized tomography (CT). CLINICAL
CASE: A 22 year old woman with no vascular risk factors was admitted to hospital
in hypoglycemic coma, after attempting suicide with oral antidiabetic drugs. The
duration of the coma was unknown. On admission the glycaemia was 28 mg/dl.
Cranial CT scan was normal during the first 24 hours. Cerebral MR scan one week
late showed hyperintense lesions in T2, basal ganglia and left hippocampus. The
cranial CT scan one year later showed diffuse atrophy, with bilateral lesions of
low attenuation in the basal ganglia and dilatation of the ventricular system.
CONCLUSIONS: It is unusual to see lesions secondary to hypoglycemia on
neuroimaging investigations. The etiopathogenic mechanism is still unknown and it
has generally been described in diabetic patients. In our case these lesions can
only be attributed to hypoglycemia. MR is more sensitive than cranial CT scan for
the detection of these lesions during the acute phase.
PMID- 9634668
TI - [A 56-year-old man with weakness of the legs].
PMID- 9634669
TI - [Cerebrovascular disease in young adults. A study of its course in 167 patients].
AB - INTRODUCTION: Few studies have been made of the prognosis of ictus in the young
adult. The objective of this paper is to study the short term evolution of 167
patients, aged between 15 and 45 years, with cerebral vascular disease. MATERIAL
AND METHODS: Since 1986 a protocolized study has been made of all patients aged
between 15 and 45 who were admitted to the Neurology Department of the Hospital
General Universitario in Valencia for a cerebral vascular incident. The results
obtained up to 1993 have been recorded in a data base. In this paper the
demographic data and information as to intrahospital evolution have been used
with the Canadian, modified Rankin and Barthel Scales in the various ictus
groups. RESULTS: 28.7% of the patients were AIT and 71.3% were diagnosed as
established ictus, of whom 38.8% were haemorrhagic and 61.2% were ischaemic.
29.8% of the HIP, 33.3% of the embolic infarcts and 18.2% of the atherothrombotic
infarcts were severely disabled on discharge from hospital. Mortality was 4.2%
when AIT were excluded. DISCUSSION: Most studies are basically aetiopathological
and much fewer include evaluation of prognosis. In our series, the patients had a
satisfactory clinical course and low short-term mortality. As in the other
series, the two groups with the worst prognosis were the HIP and the
cardioembolic infarcts. Patients with HSA and HIV made outstandingly good
progress.
PMID- 9634670
TI - [Time for cerebral damage due to hyperglycemia in acute ischemia].
AB - INTRODUCTION: Hyperglycemia increases morbimortality in cerebral infarcts. In
animal models, this relationship is only seen during the initial moments of
cerebral ischaemia. The time needed in humans for cerebral damage to occur due to
hyperglycemia is not known. MATERIAL AND METHODS: We included 194 patients
admitted within 24 hours of the start of their first clinical episode of cerebral
hemisphere infarction. The glucemia was determined on admission and after 24, 48
and 72 hours. The neurological defect was evaluated on the Canadian scale on the
seventh day. The volume of the infarct was determined on a second CT scan done
between the fourth and seventh days after the episode. RESULTS: There was a
positive association between the volume of the infarct and the glycemias on
admission and after 24 hours, but this was not seen in later determinations. The
difference in scoring, on the Canadian scale, on the seventh day, between
patients with glycemias above or below 120 mg/dl decreased from the time of
admission up to the time samples were taken 72 hours later. However, statistical
significance persisted during the whole period studied. Nevertheless, in a
logistic regression model, the glycemia on admission was the only determination
associated with the Canadian scale on the seventh day (OR = 1.02; IC 95% = 1.01
1.02). CONCLUSIONS: There is a clear association between hyperglycemia and the
worst stage of the infarct, and this is most intense in the first hours after
onset of the clinical features.
PMID- 9634671
TI - [Endovascular treatment of dural arteriovenous fistulas with medullary venous
drainage. Experience with 18 patients].
AB - INTRODUCTION AND OBJECTIVE: The authors report a series of 18 patients with
myelopathy who were diagnosed of dural arteriovenous fistulas with venous
medullary drainage (DFVMd). Purpose was to assess the effectiveness, initial and
long term, of embolization, as the initial treatment, using polyvinyl alcohol
particles (PVA) and liquid adhesives. N-butyl-cyanoacrylate (NBCA). MATERIAL AND
METHODS: Magnetic resonance images were obtained in all patients showing spinal
cord tissue changes consistent with an isquemic process secondary to venous
hypertension. All 18 patients showed initially an improvement in clinical
symptoms, demonstrating previous MR images resolution. RESULTS: The neurological
status of 8 patients subsequently deteriorated with angiographically proven
recurrences of their DFVMd. These patients underwent a second successful
embolization procedure using NBVA. PVA embolization is long term ineffective and
is not without risk. Endovascular treatment is less invasive than surgery, its
morbidity is less, and it ensures earlier recovery for the patients. If
embolization has failed, surgery can still be done. CONCLUSIONS: We recommend
that NBVA embolization be the initial treatment of choice for DFVMd if referring
the patient to an experienced interventional Neuroradiology unit is available.
Careful clinical and neurologic examination is necessary to establish the
diagnosis of DFVMd. Finally, we strongly recommend that patients be followed
closely and aggressively. Periodic clinical and radiologic assessments, including
MR and spinal angiography, are essential to achieve complete cure.
PMID- 9634672
TI - [Cardiac disease in intracerebral hematomas].
AB - INTRODUCTION AND OBJECTIVE: The Central Nervous System (CNS) plays an essential
role in the regulation of the cardiac function. There is strong evidence that
many CNS lesions, mainly those of hemorrhagic origin, may induce repolarization
abnormalities and enlargement of the QT interval (ECG changes) and several types
of arrhythmias. In some cases these changes have been related to sudden death.
The imbalance between the sympathetic and parasympathetic systems, favoring the
former, seems to be the etiopathogenic factor. MATERIAL AND METHODS: We have
carried out a study on thirty-two in-patients suffering from non-severe
intracerebral hemorrhage, by means of a Holter ECG examination within the first
72 hours and a second record after two months. We have assessed any significative
differences on the ECG findings in relation to the location of the hematoma (left
or right hemispheres) and the presence of a personal history of arterial
hypertension and/or heart disease. RESULTS: One or more ECG changes were present
in 69.2% of the patients and 73% showed one or more rhythm abnormalities. There
was a higher incidence of supraventricular arrhythmias associated with the right
hemisphere hematomas, with an statistical significance for the atrial
extrasystolia. No differences were found between the group with a previous
history of hypertension and/or heart disease and the one without these
conditions. There were two cases of sudden death, both with left hemisphere
hematomas, and in one of them the previous rhythm abnormalities were recorded.
CONCLUSIONS: This study corroborates the hypothesis that right hemispheric
hematomas induce supraventricular arrhythmias more frequently. The possible
association between severe ventricular arrhythmias and sudden death with left
hemisferic hematomas should be studied in a higher number of patients. We
recommend monitoring every acute case of intracerebral hematoma when possible.
PMID- 9634673
TI - [Autonomic and metabolic sequelae of global and focal cerebral ischemia in an
experimental model].
AB - INTRODUCTION: During the last decades the influence of cerebrovascular disease on
heart and autonomic nervous system has been studied in numerous reports.
Autonomic and metabolic changes have been described during brain ischemia.
METHODS: We studied some parameters and its modifications during global (GBI) and
focal brain ischemia (FBI). Ten Wistar rats were subjected to global ischemia and
eleven to focal brain ischemia, during 20 and 90 minutes followed in both cases
by reperfusion. Mean blood pressure, heart rate and glycaemia before, during and
after brain ischemia were registered. pH, pO2 and pCO2 were maintained within
normal range using endovenous tamponed solutions. RESULTS: During GBI the blood
pressure rose and returned to normal in the reperfusion period. Heart rate
decreased in both stroke models and hyperglycaemia was present from the beginning
in two groups. CONCLUSIONS: GBI and FBI bring about autonomic changes as
increased mean blood pressure (only in GBI) and decreased heart rate; probably
these might be explained by an autonomic nervous system disorder or by
intracranial hypertension. Hyperglycaemia could be related to cathecholamines
secretion. These effects might influence in the pathophysiology of brain
ischemia.
PMID- 9634674
TI - [Comparison of hypertensive and non-hypertensive lacunar infarcts].
AB - INTRODUCTION: Arterial hypertension and hypohyalinosis of the arterias
perforantes are said to be the commonest cause of lacunar infarcts, although
other etiological factors and anatomo-pathological lesions are described more and
more frequently. We designed a study to compare the clinical topographic and
prognostic characteristics of patients with hypertensive and non-hypertensive
lacunar infarcts. MATERIAL AND METHODS: We selected 51 patients with lacunar
infarcts: in 23 (45%) arterial hypertension was the only etiological factor
recognized. In 28 (55%) other risk factors (16 diabetes mellitus, 17 cardiopathy,
8 hyperlipemia, 13 cigarette smoking and 11 alcoholism) were seen. We evaluated
the form of presentation, the type of infarct and whether this was associated
with headache. The degree of defect was determined on admission using the
Canadian scale. The size of the infarct was measured on CT or RM, using whichever
measurement was greater. The evolution of the condition was determined on the
Canadian scale and the index of Barthel after three months. RESULTS: Age and sex
distribution was similar to both groups. Motor hemiparesia was the commonest
lacunar syndrome and the distribution was similar. There was no difference in
form of onset, association with headache or neurological defect between the
hypertensive and non-hypertensive lacunar infarcts. The topographical
distribution, the presentation of single or multiple lesions, the size of the
infarcts and the prognosis were similar in both groups. CONCLUSIONS: Lacunar
infarcts, whether hypertensive or not, show no differences regarding clinical,
neuro-radiological or evolutionary characteristics.
PMID- 9634675
TI - [Magnesium in cerebrospinal fluid in acute cerebral ischemia: its relation to
glutamate neurotoxicity].
AB - INTRODUCTION: In animal models it has been shown that there is an increase in
tissue magnesium concentration during cerebral ischemia. We studied the changes
in magnesium levels in the cerebrospinal fluid (CSF) during the acute phase of
cerebral ischemia. MATERIAL AND METHODS: We included 95 patients with first
ischemic cerebral infarcts admitted to hospital within the first 24 hours and
also 37 controls. CT scan was done on admission and between four and seven days
later (when the volume of the infarct was determined). The neurological defect
was evaluated on the Canadian scale on admission, after 48 hours, on the seventh
day and after three months. The CSF magnesium concentration was determined using
a colorimetric method and the glutamate by HPLC. RESULTS: The CSF magnesium
concentrations were significantly higher in the patients than in the controls
(2.6 +/- 0.6 mmol/l vs 2.2 +/- 0.6 mmol/l p = 0.0001). The magnesium
concentration was higher in the larger infarcts (Pearson's coefficient = 0.2901,
p = 0.0043), and in those presenting greater neurological defects after 48 hours
(Spearman's coefficient = -0.4649, p < 0.0001). The magnesium concentration was
not related to the presence of early signs on the initial CT scan and the
Canadian scale rating on admission. The concentration of magnesium was
significantly correlated with that of glutamate (Pearson coefficient = 0.7735, p
< 0.0001). CONCLUSIONS: The levels of magnesium in the CSF were satisfactorily
related to the volumes of the infarct and the intensity of the neurological
defect. However, this association was late, occurring more than 48 hours after
onset of the condition.
PMID- 9634676
TI - [Supranuclear ophthalmoplegia and walk disorders in an elderly man].
PMID- 9634677
TI - [Hip hemiplegia and parasagittal mass: different etiologies].
PMID- 9634678
TI - [Bibliographic references in REVISTA DE NEUROLOGIA in 1997].
PMID- 9634679
TI - [Evoked motor potentials in the diagnosis of conversion hysteria].
PMID- 9634680
TI - [Cuban epidemic of optic myeloneuropathy].
PMID- 9634681
TI - [Choreoathetosis: an uncommon sign of lithium poisoning].
PMID- 9634682
TI - [The importance of a therapeutic approach to families of children with cognitive
defects].
PMID- 9634683
TI - [Disability and multiple sclerosis].
PMID- 9634684
TI - [Late onset and slow course of Friedreich ataxia. A clinical electrophysiological
molecular genetic study].
PMID- 9634685
TI - [Prophylactic treatment with gabapentin in chronic daily headache resistant to
other drugs].
PMID- 9634686
TI - [Acute myocardial infarct in Switzerland: results from the PIMICS Heart Infarct
Register. PIMICS Project (Prospective Ischemia Myocardial Infarction Captopril
Survey)].
AB - The aim of the PIMICS project was to create, for the first time in Switzerland, a
registry of data concerning epidemiology and therapy in patients hospitalised for
acute myocardial infarction covering all regions of the country. During 1995/96
73 Swiss hospitals of all categories took part in the PIMICS project. The ratio
between males and females in the 3877 registered patients was 2.6:1 (2791 men vs.
1086 women). Female patients were significantly older than males (70.4 +/- 12.0
years vs. 63.4 +/- 12.6 years; p < 0.0001). The prevalence of risk factors
differed between men and women: significantly more women had hypertension or
diabetes, whereas smoking was more prevalent in males. The median delay between
onset of symptoms and arrival at the hospital was 5.5 hours. Thrombolysis and
primary angioplasty were more frequently performed in men (40.4% vs. 31.2% in
women, p < 0.0001, and 5.7% in men vs. 3.5% in women, p = 0.005 respectively).
During the acute phase males were treated more frequently with betablockers. The
overall in-hospital mortality was 9.1%. It was significantly higher in female
patients (13.5% vs. 7.4% in men; p < 0.0001) and in patients with reinfarction
(14.5% vs. 7.1%; p < 0.0001). The mean hospital stay was 12.6 +/- 5.3 days. Only
7.7% of all patients with acute myocardial infarction were discharged within 6
days. At discharge, 51.7% were treated with betablockers and 69.3% with aspirin;
44.8% received ACE-inhibitors and only 13.8% lipid-lowering drugs. Follow-up
measures such as coronary angiography and/or angioplasty or bypass surgery were
performed significantly more often in males (45.0% vs. 32.9%; p < 0.0001).
Likewise, men were more frequently assigned to a rehabilitation program than
women (38.2% vs. 32.9%; p = 0.0004). The pre-hospital delay in patients with
acute myocardial infarction remains too long. Primary and secondary prevention
should be intensified in high risk groups, particularly in females. Thrombolysis
and primary angioplasty as mainstays of treatment in acute myocardial infarction
are generally used too sparingly, especially in women. With such measures the
hospital stay could be shortened further.
PMID- 9634687
TI - [Tuberculosis: contact tracing and preventive chemotherapy].
AB - Tuberculosis is transmitted from patients with lung disease to sensitive
individuals by inhalation of infectious particles expelled during cough.
Therefore, the search for infected subjects among relatives of patients with
infectious tuberculosis is the best method of preventing later development of the
disease in populations where the prevalence of tuberculosis is low. Contact
tracing relies on the tuberculin skin test, followed by chest X-ray if indicated
and bacteriological examination of sputum. In recently infected subjects,
particularly the young, preventive chemotherapy has been shown to decrease the
risk of later disease.
PMID- 9634688
TI - [Diagnostic approach to pulmonary embolism].
AB - Despite its relatively high frequency, pulmonary embolism remains difficult to
diagnose due to its non-specific symptomatology and the diagnostic uncertainties
of the paraclinical tests used. The diagnostic approach is based initially on
evaluation of the a priori clinical probability of thromboembolic disease, then
on a decisional strategy regarding the choice of the most efficient paraclinical
tests. The specific characteristics of the paraclinical tests are reviewed. A
series of decisional algorithms is proposed based on the notion that pulmonary
embolism and deep-vein thrombosis are two facets of the same disease. In the
majority of cases, performing invasive tests such as pulmonary angiography and
phlebography of the legs become less necessary with the use of the proposed
strategies, which serve to identify the patients to be treated as well as those
who do not require anticoagulant therapy.
PMID- 9634689
TI - [Physician's attitude to acute non-cardiac thoracic pain].
AB - Acute non-cardiac chest pain is very commonly reported in ambulatory care or
hospitalized patients. Most cases arise from non-organic causes and should be
treated by the primary care physician after having reasonably excluded curable or
potentially life-threatening diseases. This new approach is designed to save
costly and unnecessary investigations and more effectively assist patients
suffering from acute non-cardiac chest pain due to anxiety disorders.
PMID- 9634690
TI - [Solitary fibrous tumor of the pleura with signs of malignancy].
PMID- 9634691
TI - Structural principles in cell-cycle control: beyond the CDKs.
AB - Retinoblastoma protein (Rb) interacts with cyclin-dependent kinases and regulates
the transcription of genes necessary for progression through the S phase of the
cell cycle. Clues to the atomic mechanisms involved are offered by the structure
of the two pocket regions of Rb in complex with a short peptide from a viral
oncoprotein. Structures of cyclins, Rb and TFIIB reveal that a common motif
occurs in proteins regulating three consecutive events of cell-cycle control.
PMID- 9634692
TI - Teaching a new dog old tricks?
AB - The recently determined crystal structures of fragments of the human and vaccinia
virus type IB topoisomerases reveal unexpected similarity with the lambda family
of site-specific recombinases. The conservation of structure suggests a common
mechanism, indicating that topoisomerase activity may be the consequence of
uncoupling DNA strand cleavage/religation from synapsis.
PMID- 9634693
TI - Transcriptional cooperativity: bending over backwards and doing the flip.
AB - The structures of the NFAT1-Fos-Jun-ARRE2 and MAT alpha 2-MCM1-STE6 transcription
regulatory complexes reveal changes in protein conformation and DNA bending.
Studies of the interaction between Fos-Jun and NFAT1 in solution corroborate the
crystallographic analysis. These results manifest the flexibility required for
cooperative binding to composite regulatory elements.
PMID- 9634694
TI - High-resolution structure of an archaeal zinc ribbon defines a general
architectural motif in eukaryotic RNA polymerases.
AB - BACKGROUND: Transcriptional initiation and elongation provide control points in
gene expression. Eukaryotic RNA polymerase II subunit 9 (RPB9) regulates start
site selection and elongational arrest. RPB9 contains Cys4 Zn(2+)-binding motifs
which are conserved in archaea and homologous to those of the general
transcription factors TFIIB and TFIIS. RESULTS: The structure of an RPB9 domain
from the hyperthermophilic archaeon Thermococcus celer was determined at high
resolution by NMR spectroscopy. The structure consists of an apical tetrahedral
Zn(2+)-binding site, central beta sheet and disordered loop. Although the
structure lacks a globular hydrophobic core, the two surfaces of the beta sheet
each contain well ordered aromatic rings engaged in serial edge-to-face
interactions. Basic sidechains are clustered near the Zn(2+)-binding site. The
disordered loop contains sidechains conserved in TFIIS, including acidic residues
essential for the stimulation of transcriptional elongation. CONCLUSIONS: The
planar architecture of the RPB9 zinc ribbon-distinct from that of a conventional
globular domain-can accommodate significant differences in the alignment of
polar, non-polar and charged sidechains. Such divergence is associated with local
and non-local changes in structure. The RPB9 structure is distinguished by a
fourth beta strand (extending the central beta sheet) in a well ordered N
terminal segment and also differs from TFIIS (but not TFIIB) in the orientation
of its apical Zn(2+)-binding site. Cys4 Zn(2+)-binding sites with distinct
patterns of polar, non-polar and charged residues are conserved among unrelated
RNAP subunits and predicted to form variant zinc ribbons.
PMID- 9634695
TI - Structure of an aromatic-ring-hydroxylating dioxygenase-naphthalene 1,2
dioxygenase.
AB - BACKGROUND: Pseudomonas sp. NCIB 9816-4 utilizes a multicomponent enzyme system
to oxidize naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. The
enzyme component catalyzing this reaction, naphthalene 1,2-dioxygenase (NDO),
belongs to a family of aromatic-ring-hydroxylating dioxygenases that oxidize
aromatic hydrocarbons and related compounds to cis-arene diols. These enzymes
utilize a mononuclear non-heme iron center to catalyze the addition of dioxygen
to their respective substrates. The present study was conducted to provide
essential structural information necessary for elucidating the mechanism of
action of NDO. RESULTS: The three-dimensional structure of NDO has been
determined at 2.25 A resolution. The molecule is an alpha 3 beta 3 hexamer. The
alpha subunit has a beta-sheet domain that contains a Rieske [2Fe-2S] center and
a catalytic domain that has a novel fold dominated by an antiparallel nine
stranded beta-pleated sheet against which helices pack. The active site contains
a non-heme ferrous ion coordinated by His208, His213, Asp362 (bidentate) and a
water molecule. Asn201 is positioned further away, 3.75 A, at the missing axial
position of an octahedron. In the Rieske [2Fe-2S] center, one iron is coordinated
by Cys81 and Cys101 and the other by His83 and His104. CONCLUSIONS: The domain
structure and iron coordination of the Rieske domain is very similar to that of
the cytochrome bc1 domain. The active-site iron center of one of the alpha
subunits is directly connected by hydrogen bonds through a single amino acid,
Asp205, to the Rieske [2Fe-2S] center in a neighboring alpha subunit. This is
likely to be the main route for electron transfer.
PMID- 9634696
TI - Characterizing global substates of myoglobin.
AB - BACKGROUND: The massive amount of information generated from current molecular
dynamics simulations makes the data difficult to analyze efficiently. Principal
component analysis has been used for almost a century to detect and characterize
data relationships and to reduce the dimensionality for problems in many fields.
Here, we present an adaptation of principal component analysis using a partial
singular value decomposition (SVD) for investigating both the localized and
global motions of macromolecules. RESULTS: Configuration space projections from
the SVD analysis of a variety of myoglobin simulations are used to characterize
the dynamics of the protein. This technique reveals new dynamical motifs, which
quantify proposed hierarchical structures of conformational substates for
proteins and provide a means by which configuration space sampling efficiency may
be probed. The SVD clearly shows that solvent effects facilitate transitions
between global conformational substates for myoglobin molecular dynamics
simulations. Lyapunov exponents calculated from the configuration space
divergence of 15 trajectories agree with previous predictions for the chaotic
behavior of complex protein systems. CONCLUSIONS: Configuration space projections
provide invaluable information about protein motions that would be extremely
difficult to obtain otherwise. While the configuration space for myoglobin is
quite large, it does have structure. Our analysis of this structure shows that
the protein hops between a number of distinct global conformational states, much
like the local behavior observed for an individual residue.
PMID- 9634697
TI - Crystal structure of the receptor-binding domain of alpha 2-macroglobulin.
AB - BACKGROUND: The large plasma proteinase inhibitors of the alpha 2-macroglobulin
superfamily inhibit proteinases by capturing them within a central cavity of the
inhibitor molecule. After reaction with the proteinase, the alpha-macroglobulin
proteinase complex binds to the alpha-macroglobulin receptor, present in the
liver and other tissues, and becomes endocytosed and rapidly removed from the
circulation. The complex binds to the receptor via recognition sites located on a
separate domain of approximately 138 residues positioned at the C terminus of the
alpha-macroglobulin subunit. RESULTS: The crystal structure of the receptor
binding domain of bovine alpha 2-macroglobulin (bRBD) has been determined at a
resolution of 1.9 A. The domain primarily comprises a nine-strand beta structure
with a jelly-roll topology, but also contains two small alpha helices.
CONCLUSIONS: The surface patch responsible for receptor recognition is thought to
involve residues located on one of the two alpha helices of the bRBD as well as
residues in two of the beta strands. Located on this alpha helix are two lysine
residues that are important for receptor binding. The structure of bRBD is very
similar to the approximately 100-residue C-terminal domain of factor XIII, a
transglutaminase from the blood coagulation system.
PMID- 9634698
TI - The crystal structure of phenol hydroxylase in complex with FAD and phenol
provides evidence for a concerted conformational change in the enzyme and its
cofactor during catalysis.
AB - BACKGROUND: The synthesis of phenolic compounds as by-products of industrial
reactions poses a serious threat to the environment. Understanding the enzymatic
reactions involved in the degradation and detoxification of these compounds is
therefore of much interest. Soil-living yeasts use flavin adenine dinucleotide
(FAD)-containing enzymes to hydroxylate phenols. This reaction initiates a
metabolic sequence permitting utilisation of the aromatic compound as a source of
carbon and energy. The phenol hydroxylase from Trichosporon cutaneum hydroxylates
phenol to catechol. Phenol is the best substrate, but the enzyme also accepts
simple hydroxyl-, amino-, halogen- or methyl-substituted phenols. RESULTS: The
crystal structure of phenol hydroxylase in complex with FAD and phenol has been
determined at 2.4 A resolution. The structure was solved by the MIRAS method. The
protein model consists of two homodimers. The subunit consists of three domains,
the first of which contains a beta sheet that binds FAD with a typical beta alpha
beta nucleotide-binding motif and also a fingerprint motif for NADPH binding. The
active site is located at the interface between the first and second domains; the
second domain also binds the phenolic substrate. The third domain contains a
thioredoxin-like fold and is involved in dimer contacts. The subunits within the
dimer show substantial differences in structure and in FAD conformation. This
conformational flexibility allows the substrate to gain access to the active site
and excludes solvent during the hydroxylation reaction. CONCLUSIONS: Two of the
domains of phenol hydroxylase are similar in structure to p-hydroxybenzoate
hydroxylase. Thus, phenol hydroxylase is a member of a family of flavin
containing aromatic hydroxylases that share the same overall fold, in spite of
large differences in amino acid sequences and chain length. The structure of
phenol hydroxylase is consistent with a hydroxyl transfer mechanism via a peroxo
FAD intermediate. We propose that a movement of FAD takes place in concert with a
large conformational change of residues 170-210 during catalysis.
PMID- 9634699
TI - The structural basis of ankyrin-like repeat function as revealed by the solution
structure of myotrophin.
AB - BACKGROUND: Myotrophin is a 12.5 kDa protein that appears to have a key role in
the initiation of cardiac hypertrophy, a central process in many heart diseases.
Myotrophin primarily comprises ankyrin-like (ANK) repeats, the 33 amino acid
motifs involved in a wide range of protein-protein interactions. As a first step
in the structure-based search for cardiac hypertrophy antagonists and in order to
gain insight into the molecular basis of action of the ubiquitous and
multifunctional ANK repeat motif, we have determined the solution structure of
myotrophin using multidimensional heteronuclear NMR spectroscopy. RESULTS: The
myotrophin structure determination was based on 2786 experimental NMR restraints,
and the precision of the coordinates for the final 45 simulated-annealing
structures is 0.43 A for the backbone atoms and 0.87 A for all atoms. The
structure of myotrophin is well defined and is ellipsoidal: approximately 46 A
long and 21 A wide. The ANK repeats, which constitute the main part of the
myotrophin structure, are characteristic of a hairpin-like protruding tip
followed by a helix-turn-helix motif. The V-shaped helix-turn-helix of the ANK
repeats stack sequentially in bundles and are stabilized by compact hydrophobic
cores, whereas the protruding tips are less ordered. This arrangement is quite
different to the continuous beta-sheet topology observed in the corresponding
regions of another ANK protein, 53BP2, the structure of which was determined in
complex with p53. CONCLUSIONS: The solution structure of myotrophin provides
important insights into the structural and dynamic features of the ANK motif, and
suggests that the protruding tips with highly variable sequences may be critical
to facilitate diverse protein-protein recognition. The present structure also
provides a molecular basis for the further functional characterization of
myotrophin and the development of therapeutics for hypertrophy-related heart
diseases.
PMID- 9634700
TI - Interfering with the inhibitory mechanism of serpins: crystal structure of a
complex formed between cleaved plasminogen activator inhibitor type 1 and a
reactive-centre loop peptide.
AB - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is an important
endogenous regulator of the fibrinolytic system. Reduction of PAI-1 activity has
been shown to enhance dissolution of blood clots. Like other serpins, PAI-1 binds
covalently to a target serine protease, thereby irreversibly inactivating the
enzyme. During this process the exposed reactive-centre loop of PAI-1 is believed
to undergo a conformational change becoming inserted into beta sheet A of the
serpin. Incubation with peptides from the reactive-centre loop transform serpins
into a substrate for their target protease. It has been hypothesised that these
peptides bind to beta sheet A, thereby hindering the conformational rearrangement
leading to loop insertion and formation of the stable serpin-protease complex.
RESULTS: We report here the 1.95 A X-ray crystal structure of a complex of a
glycosylated mutant of PAI-1, PAI-1-ala335Glu, with two molecules of the
inhibitory reactive-centre loop peptide N-Ac-TVASS-NH2. Both bound peptide
molecules are located between beta strands 3A and 5A of the serpin. The binding
kinetics of the peptide inhibitor to immobilised PAI-1-Ala335Glu, as monitored by
surface plasmon resonance, is consistent with there being two different binding
sites. CONCLUSIONS: This is the first reported crystal structure of a complex
formed between a serpin and a serpin inhibitor. The localisation of the
inhibitory peptide in the complex strongly supports the theory that molecules
binding in the space between beta strands 3A and 5A of a serpin are able to
prevent insertion of the reactive-centre loop into beta sheet A, thereby
abolishing the ability of the serpin to irreversibly inactivate its target
enzyme. The characterisation of the two binding sites for the peptide inhibitor
provides a solid foundation for computer-aided design of novel, low molecular
weight PAI-1 inhibitors.
PMID- 9634701
TI - Solution structure of the heparin-binding domain of vascular endothelial growth
factor.
AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell
specific mitogen and is a potent angiogenic and vascular permeabilizing factor.
VEGF is also an important mediator of pathological angiogenesis associated with
cancer, rheumatoid arthritis and proliferative retinopathy. The binding of VEGF
to its two known receptors, KDR and Flt-1, is modulated by cell-surface
associated heparin-like glycosaminoglycans and exogenous heparin or heparan
sulfate. Heparin binding to VEGF165, the most abundantly expressed isoform of
VEGF, has been localized to the carboxy-terminal 55 residues; plasmin cleavage of
VEGF165 yields a homodimeric 110-residue amino-terminal receptor-binding domain
(VEGF110) and two 55-residue carboxy-terminal heparin-binding fragments. The
endothelial cell mitogenic potency of VEGF110 is decreased significantly relative
to VEGF165, indicating that the heparin-binding domains are critical for
stimulating endothelial cell proliferation. RESULTS: The solution structure of
the 55-residue heparin-binding domain of VEGF165 has been solved using data from
two-dimensional homonuclear and three-dimensional heteronuclear NMR spectroscopy.
The structure has two subdomains, each containing two disulfide bridges and a
short two-stranded antiparallel beta sheet; the carboxy-terminal subdomain also
contains a short alpha helix. Hydrophobic interactions are limited to sidechains
packing against the disulfide bridges. CONCLUSIONS: The heparin-binding domain of
VEGF has no significant sequence or structural similarity to any known proteins
and thus represents a novel heparin-binding domain. Most of the positively
charged amino acid sidechains are localized on one side of the carboxy-terminal
subdomain or on an adjacent disordered loop in the amino-terminal subdomain. The
observed distribution of surface charges suggests that these residues constitute
a heparin interaction site.
PMID- 9634702
TI - Barley alpha-amylase bound to its endogenous protein inhibitor BASI: crystal
structure of the complex at 1.9 A resolution.
AB - BACKGROUND: Barley alpha-amylase is a 45 kDa enzyme which is involved in starch
degradation during barley seed germination. The released sugars provide the plant
embryo with energy for growth. The major barley alpha-amylase isozyme (AMY2)
binds with high affinity to the endogenous inhibitor BASI (barley alpha
amylase/subtilisin inhibitor) whereas the minor isozyme (AMY1) is not inhibited.
BASI is a 19.6 kDa bifunctional protein that can simultaneously inhibit AMY2 and
serine proteases of the subtilisin family. This inhibitor may therefore prevent
degradation of the endosperm starch during premature sprouting and protect the
seed from attack by pathogens secreting proteases. RESULTS: The crystal structure
of AMY2 in complex with BASI was determined and refined at 1.9 A resolution. BASI
consists of a 12-stranded beta-barrel structure which belongs to the beta-trefoil
fold family and inhibits AMY2 by sterically occluding access of the substrate to
the active site of the enzyme. The AMY2-BASI complex is characterized by an
unusual completely solvated calcium ion located at the protein-protein interface.
CONCLUSIONS: The AMY2-BASI complex represents the first reported structure of an
endogenous protein-protein complex from a higher plant. The structure of the
complex throws light on the strict specificity of BASI for AMY2, and shows that
domain B of AMY2 contributes greatly to the specificity of enzyme-inhibitor
recognition. In contrast to the three-dimensional structures of porcine
pancreatic alpha-amylase in complex with proteinaceous inhibitors, the AMY2-BASI
structure reveals that the catalytically essential amino acid residues of the
enzyme are not directly bound to the inhibitor. Binding of BASI to AMY2 creates a
cavity, exposed to the external medium, that is ideally shaped to accommodate an
extra calcium ion. This feature may contribute to the inhibitory effect, as the
key amino acid sidechains of the active site are in direct contact with water
molecules which are in turn ligated to the calcium ion.
PMID- 9634704
TI - Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie.
AB - Preliminary findings have indicated that in naturally infected sheep, fully
susceptible to scrapie (VRQ-homozygous), PrPSc can be detected in the tonsils
approximately one year before the expected onset of clinical disease, whereas no
immunostaining can be detected in animals with a semi-resistant genotype. This
paper describes the technique for taking tonsillar biopsies from sheep and gives
the results of the completed experiment. In another experiment PrPSc was detected
even earlier in comparable VRQ-homozygous sheep born and raised in different
surroundings. At three-and-a-half months of age no PrPSc could be detected in
three homozygous susceptible sheep (VRQ/VRQ), but PrPSc was detected at four
months in one similar sheep. At eight months of age all seven sampled VRQ/VRQ
sheep showed positive immunostaining in the biopsies, but none of the biopsies
from three VRQ/ARQ heterozygotes showed any immunostaining; they were positive
when sampled at 14 to 15 months of age. Biopsies from VRQ/ARR sheep were negative
throughout this period. On the basis of the established or expected incubation
period, PrPSc could thus be detected in the tonsils of live susceptible animals
at between one-third and a half of the incubation period, more than one-and-a
half years before clinical signs normally appear in both these genotypes.
PMID- 9634703
TI - Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A
resolution.
AB - BACKGROUND: The sterol regulatory element binding proteins (SREBPs) are helix
loop-helix transcriptional activators that control expression of genes encoding
proteins essential for cholesterol biosynthesis/uptake and fatty acid
biosynthesis. Unlike helix-loop-helix proteins that recognize symmetric E-boxes
(5'-CANNTG-3'), the SREBPs have a tyrosine instead of a conserved arginine in
their basic regions. This difference allows recognition of an asymmetric sterol
regulatory element (StRE, 5'-ATCACCCAC-3'). RESULTS: The 2.3 A resolution co
crystal structure of the DNA-binding portion of SREBP-1a bound to an StRE reveals
a quasi-symmetric homodimer with an asymmetric DNA-protein interface. One monomer
binds the E-box half site of the StRE (5'-ATCAC-3') using sidechain-base contacts
typical of other helix-loop-helix proteins. The non-E-box half site (5'-GTGGG-3')
is recognized through entirely different protein-DNA contacts. CONCLUSIONS:
Although the SREBPs are structurally similar to the E-box-binding helix-loop
helix proteins, the Arg-->Tyr substitution yields dramatically different DNA
binding properties that explain how they recognize StREs and regulate expression
of genes important for membrane biosynthesis.
PMID- 9634705
TI - Attempted elimination of porcine reproductive and respiratory syndrome virus from
a seedstock farm by vaccination of the breeding herd and nursery depopulation.
AB - An attempt was made to eliminate the virus of porcine reproductive and
respiratory syndrome from a seedstock farm by using the combined strategies of
vaccination and nursery depopulation. The breeding herd was vaccinated with a
modified-live virus vaccine; all breeding and lactating adult animals were
vaccinated twice, with a 30-day interval between vaccinations. All the sows were
vaccinated in this way except for those in the third trimester of gestation (66
to 114 days) which were vaccinated on day 7 of lactation and 30 days later. A
serological profiling system was developed to assess when the piglets became
infected. Pigs from vaccinated sows were profiled at weekly intervals after
weaning, using immunofluorescence tests for the detection of IgM and IgG, a serum
neutralising antibody test, and virus isolation. After completion of the
protocol, the nursery and finishing sites were monitored for 15 months. Evidence
of reinfection in the finishing stage was detected 16 months after depopulation,
but not in the nursery or the breeding herd. The source of the virus was not
determined, but suspected origins included a lack of biosecurity, aerosol
transmission from another infected farm or a persistently infected pig.
PMID- 9634706
TI - Assessment of the modified Forssell's procedure for the treatment of oral
stereotypies in 10 horses.
AB - The modified Forssell's procedure was performed on 10 horses in an attempt to
cure oral stereotypies. Three horses were cured completely, two horses were
considerably improved, and five horses continued to perform the stereotypy after
periods of remission ranging from two weeks to six months. This rate of success
for the modified Forssell's procedure, as in other published reports, was lower
than for the original Forssell's procedure. Surgery to eliminate a stereotypical
behaviour pattern may exacerbate the stress for an animal and the modified
Forssell's procedure can no longer be recommended for the treatment of oral
stereotypies in horses.
PMID- 9634707
TI - Comparison of three treatments for bovine endometritis.
AB - Three commercial preparations for the treatment of bovine endometritis were
compared: an intrauterine infusion of 1500 mg oxtytetracycline hydrochloride
solution, an intramuscular injection of 500 micrograms cloprostenol (a synthetic
analogue of prostaglandin F2 alpha), and an intramuscular injection of 3 mg
oestradiol benzoate/500 kg estimated bodyweight. A total of 300 cases of
endometritis were treated, of which 225 involved first, 67 involved second, and
eight involved third or subsequent treatments. The overall success rate of
treatment was 68 per cent. Oxytetracycline was successful in 73 per cent of
cases, cloprostenol in 67 per cent and oestradiol in 63 per cent of cases. There
was no significant difference between the success rates of the treatments, except
for cows with mild endometritis in which oxytetracycline was more successful than
oestradol (86 v 66 per cent, P < 0.05). Mild cases were treated more successfully
than moderate cases (78 v 61 per cent, P < 0.01), and more successfully than
severe cases (78 v 44 per cent, P < 0.001). Prostaglandin F2 alpha was more
successful if the milk progesterone concentration was > 7 ng/ml at the time of
treatment (P < 0.05). The presence of a smelly discharge at the time of treatment
reduced the success rate by 17 per cent (P < 0.02). The treatment to conception
interval for all successful treatments of endometritis by prostaglandin F2 alpha
was 18.1 days shorter than for oestradiol (68.3 v 86.4 days, P < 0.02), and the
interval for oxytetracycline was 16.2 days shorter than for oestradiol (70.2 v
86.4 days, P < 0.05).
PMID- 9634708
TI - Maternal transmission of BSE: interpretation of the data on the offspring of BSE
affected pedigree suckler cows.
PMID- 9634709
TI - Bronchobiliary fistula in two adult cattle.
PMID- 9634710
TI - Uterine drainage under general anaesthesia before ovariohysterectomy in two
mares.
PMID- 9634711
TI - Funding veterinary education.
PMID- 9634712
TI - Use of clomipramine for separation anxiety in dogs.
PMID- 9634713
TI - Conformation defects in draught donkeys.
PMID- 9634714
TI - [Potentially dangerous photosensitizers among drugs and medicinal plant
extracts].
AB - The review deals with photosensitizing properties of drugs and plant extracts.
Some compounds are able to cause side effects such as phototoxicity and
photoallergy. Revealing and study of harmful photosensitizers is actual problem
in connection with changing photoecological situation.
PMID- 9634716
TI - [Effect of prenatal gamma-irradiation on functional properties of rat liver
adenylate cyclase].
AB - In the present work the effects of long-term prenatal gamma-irradiation (0.5 Gy)
on the glucagon signalling through adenylyl cyclase have been investigated. In
utero gamma-irradiation resulted in the increase of basal and GTP-stimulated
adenylyl cyclase activity, whereas, the adenylyl cyclase response to glucagon was
essentially reduced. The comparison of kinetic constants estimated from dose
response data for GTP and glucagon suggests that prenatal chronic irradiation
prompted (i) the decrease in rate of GTP hydrolysis on Gs-protein; (ii) the
reduction of glucagon potency to accelerate the exchange GDP for GTP on Gs
protein.
PMID- 9634715
TI - [Sulfated polysaccharides as inhibitors of receptor activity of P-selectin and P
selectin-dependent inflammation].
AB - The inhibitory effects of sulfated polysaccharides-fucoidan and heparin on P
selectin-ligand interaction in vitro and on the ability of fucoidan to inhibit
the leukocyte extravasation in rat peritonitis were studied. The lectin activity
of P-selectin in vitro was based on its ability to bind lectin-labeled synthetic
ligand, Sialyl-Lea/x, conjugated with polyacrylamide (PAA). Fucoidan and heparin
inhibited binding of labeled ligand to both purified P-selectin and the activated
platelets expressing P-selectin on their surface. The inhibitory effect of
fucoidan 100-fold higher than that of heparin. As P-selectin plays an important
role at an earlier stage of the inflammation process, the antiinflammatory action
of fucoidan on P-selectin-dependent peritonitis in rats was studied. Peritonitis
was induced by intraperitoneal injection of the peptone solution and was
characterized by an increase in total cell number and neutrophil percentage in
rat peritone exudate. Intravenous injection of fucoidan was found to cause a dose
and time-dependent reduction of neutrophil extravasation into inflamed
peritoneum. The minimal dose of fucoidan, that was able to produce 96.8 +/- 2.9%
inhibition of neutrophil extravasation--if administered within the first 15 min
after peptone-B was 0.8 mg per rat. Significant effect of fucoidan injection
(about 80% inhibition) was also obtained 1.5 h after the induction of
inflammation. Fucoidan administered 2.5 h after peptone had virtually no effect
on neutrophil extravasation. The data obtained show that fucoidan blocks the
inflammation process at its earlier stages--most probably at the expense of its
interaction with P-selectin.
PMID- 9634717
TI - [Dual reciprocal regulation of the succinate oxidation system in heart and liver
mitochondria in pathological conditions].
AB - The phenomenon of the dual reciprocal regulation of succinate dependent 2H+/Ca2+
exchange was studied in heart and liver mitochondria of experimental animals
(allogenic heart transplantation in rat; myocardium infarction in rabbits;
pulmonary arteria coarctation in dogs) and in liver bioptates from patients with
stomach ulcer. Under pathology two coupled but opposite changes (simultaneous
activation and inhibition) in succinate dependent Ca2+ transport occur. The
inhibition of Ca2+ transport was detected by its elimination with glutamate,
being mostly pronounced after cycle of ADP phosphorylation added to suspension of
mitochondria. The treatment of animal with 2-oxoglutarate abolished this
inhibition. This was not observed in healthy animals. The described phenomenon
can prevent hyperactivation of succinate oxidation under strong pathological
(distress) influences.
PMID- 9634718
TI - [Accumulation of vitamin E in dimethylnitrosamine-induced kidney tumors in rats
with various levels of alpha-tocopherol supplementation].
AB - The effect of a long-lasting loading with alpha-tocopherol on the development of
dimethylnitrosamine-induced kidney tumors was investigated in 55 non-bred white
male rats. The carcinogen was repeatedly introduced into the stomach by means of
a gastric tube. Starting 24 days after the last administration of the carcinogen
the alpha-tocopherol loading began and lasted up to the end of the experiment. 21
rats were loaded with vitamin E introduced into the stomach, 5 times a week at a
dose of 70 mg/kg body weight. 17 rats received sunflower seed oil--the vitamin E
solvent; other 17 rats received only standard ration. The control group (20 rats)
were not treated with the carcinogen. One part of these rats received alpha
tocopherol by the above schedule while another part--sunflower oil alone. It was
shown that the alpha-tocopherol loading had no effect on the incidence of renal
tumors. Nevertheless it enhanced to some extent the rate of their development as
well as the incidence of blastomes in other organs. Based on histological
examination, tumors developed in kidneys were of epithelial and mesenchymal
origins with the mesenchymal tumors occurring more frequently (63-69% of the
total). Vitamin E content in tumor tissue of rats, loaded or not loaded with
alpha-tocopherol, was much higher than that in intact kidneys of corresponding
control animals, suggesting a high tumor tropism of this vitamin. Total lipid
concentration of tumor tissue was 1.5 times lower than that of intact kidneys.
Histological nature of tumors had no visible effect on their vitamin E and total
lipid content.
PMID- 9634719
TI - [Dynamics of accumulation of CYP2B mRNA in the liver of rats from various strains
during induction with xenobiotics].
AB - The transcription level of CYP2B1/2 gene in the liver of Sprague-Dawley (SD),
Brattleboro (BL) and Wistar (W) rats treated with isosafrol (IS), Arochlor 1254
(AC), phenobarbital (PB) and triphenildioxane (TPD) was studied. The quantity of
CYP2B1/2 mRNA was assessed by dot-blot analysis at 18, 48 and 72 hours after
inducers administration. The mRNA level in SD and BL rats treated with PB reached
its maximum by 18 hours followed by fast decline. For W strain the amount of mRNA
reached maximum by 48 hours after treatment. After TPD treatment this parameter
for SD, W rats reached maximum by 18 hours, while for BL-72 hours. No differences
in the mRNA amount in rats treated with IS and AC were detected. We are not aware
of any other data concerning the dynamics of CYP2B1/2 mRNA accumulation during IS
induction. We showed that in this case a maximum of mRNA was reached by 18 hours.
Thus, we revealed inducer- and strain-dependent of differences in mRNA
accumulation dynamics.
PMID- 9634720
TI - [Determination of a Candida albicans antigen using an amperometric immunoenzyme
sensor].
AB - Determination new variant enzyme immunoassay with amperometric enzyme
immunosensor, including the immobilizing enzyme-choline esterase and antibodies
against Candida albicans (CA) in biosensitivity part of sensor, for diagnose
disease of CA. The method for determination of CA based on combination
immunochemical reactions and voltammetric indication of analytical signal was
developed. Amperometric enzyme immunosensor developed has been used as detector.
Differences dilutions of antibody (Ab) against antigen (Ag) of CA immobilizing in
common with choline esterase (CE). The method of immobilization developed allows
to receive the sensor with including the immobilized CE and Ab in common. The
method of determination of CA based on combination the reaction of forming immune
complex tAb-AgI with enzyme immunosensor for its detection. The dynamic range of
concentrations determined of Ag depends on degree of dilution of Ab used for
manufactory biosensitivity part of sensor. The data indicate that the [Ab-Ag]
immune complexes are stable. This is also confirmed by the values of [Ab-Ag]
binding constants, obtained in Scatchard coordinates. This method of
determination doesn't require special preparation of a sample. Selectivity,
sensitivity, simplicity and quickness are characterize of this method which could
be used for manufacturing test-sistem for determination CA in blood.
PMID- 9634721
TI - [Classification of drugs by biochemical mechanism of action].
AB - Biochemical drugs classification is proposed. Drugs are divided into 6 classes,
according to their action on: 1) signal-transduction systems, 2) other components
of plasmatic membranes, 3) intracellularly, 4) gene therapy, 5) extracellularly,
6) invasive agents. Concrete biochemical mechanisms of action of every class
drugs are considered and described.
PMID- 9634722
TI - [Quantitative dependence of structure-antiseizure activity in a series of
macrocyclic compounds].
AB - In the present study we have further examined the influence of some structure
parameters of macrocyclic polyethers upon their anticonvulsant activity in order
to determine basic pharmacophore fragments. The anticonvulsant activity was
studied experimentally for 25 new macrocyclic compounds, and their structure,
physico-chemical properties, electron donor factors and atom charges were
calculated using programs HyperChem-ChemPlus and HYBOT. The data about atomic
properties were presented as a set functions of inter-atomic distances (Program
MOLTRA). The cluster analysis revealed that studied compounds represent two
independent groups which differ from chemical and pharmacological viewpoints. For
first group, we have found that anticonvulsant activity of macrocycles is
determined by their polarizability and spatial orientation of electron donor
atoms. For another cluster the correlation was found between activity and spatial
orientation of two hydrophobic fragments and electron donor atoms as well.
PMID- 9634723
TI - [Solid-phase immunoenzyme analysis of chloramphenicol in human blood serum].
AB - The method of enzyme linked immunosorbent assay (ELISA) for quantitative
detection of chloramphenicol (CAP) in human blood serum was developed.
Peculiarities of the adsorption on the microtitre plates surface of CAP-ovalbumin
conjugate were investigated. Different conditions of competition stage of the
analysis were studied. Conditions providing CAP monitoring in human blood serum
in the clinical range were optimized. Matrix effect on the assay results was
studied. The specificity of the analytical system was investigated and the
reagents stability was examined. The method developed permits CAP concentration
to be determined in human blood serum, diluted 1/100, in the linear range from 10
to 1000 ng/ml. The assay is characterized by high sensitivity (1 ng/mL) and good
reproducibility (CV < 12%), assay time is about 3 hours.
PMID- 9634724
TI - [Possible participation of angiotensin-converting enzyme and leukocyte elastase
in the pathogenesis of insulin-independent diabetes mellitus].
AB - It is commonly accepted that the tolerance to insulin and hyperglycemia of the
patients with non-insulin dependent diabetes mellitus (NIDDM) is due to some
defect of insulin receptors or disturbances in the signaling pathway of the cell.
This disease is often accompanied by hypertension. In this paper the high
activity of plasma kallikrein-kinin system (KKS) (kallikrein activity was 6-8
times higher than normal), of angiotensin-converting enzyme (ACE) (4 times
greater than normal), and of leukocyte elastase (2.7 times higher than normal)
were demonstrated in plasma of patients with NIDDM. Increasing of KKS activity
was coincident with rising of ACE activity, which may be the cause of the fast
bradykinin inactivation and arising of hypertension. The treatment with ACE
inhibitor during 3 months (4 mg of Perindopril per day) decreased ACE activity in
patients' plasma which was accompanied with decreasing of the arterial pressure
and some restoration of the carbohydrate metabolism indicators. The
hyperinsulinemic euglycaemic clamping of 7 patients with NIDDM and essential
hypertension showed that ACE-inhibitor (Perindopril, 4 mg) prevented bradykinin
from destruction and increased the glucose consumption by tissues. The high
activity of polymorphonuclear leukocytes and secretion of the elastase in NIDDM
patients' plasma and/or instability of plasmatic and granular membranes of
leukocyte in conditions of hyperglycaemic plasma are probably the cause of
endothelial irritation and high ACE secretion. Secondly, the leukocyte may be the
cause of injuring and decreasing of susceptibility of the cell receptors for
insulin and bradykinin.
PMID- 9634725
TI - [Relationship of the levels of arachidonic and eicosapentaenoic acid in blood
serum and low density lipoproteins in patients with bronchial asthma and change
in the value during restricted-diet therapy].
AB - Lipid metabolism in patients with infection-dependent bronchial asthma was
compared before and after 14 days low-diet therapy. After therapy the proportion
AA/EPA in blood serum and in low density lipoproteins considerably decreased to
(p < 0.05).
PMID- 9634726
TI - [The role of neurosurgery in the study of brain-mind relationship].
PMID- 9634727
TI - [Contemporary trends in the development of psychopharmacotherapy].
AB - Modern period of psychopharmacology development is characterized by seven main
features: changes in both clinical picture and course of psychic diseases; the
use of psychotropic drug in general medicine; some new nosologic entities in ICD
10 which require of more accurate definition of the methods of therapy; progress
in the study of biologic mechanisms of psychotropic drugs' action; appearance of
numerous little-known preparations; discovery of some new aspects in action of
well-known drugs; increase of the number of patients resistent to
psychopharmacotherapy. Traditional and original classifications of psychotropic
drugs are presented. Clinical analysis revealed that clear limits between
separate groups of drugs are relative. Between the separate classes
"transitional" drugs exist with distinct properties of both groups. Such drugs
are thymoneuroleptics, thymotranquilizers, antidepressants with nootropic and
neuroleptic properties, tranquilonootrops, etc. In accordance with the conception
of "ideal" drug each class of psychotropic drugs was analyzed in terms of main
advantages and defects. The advantages of some new drugs are considered.
PMID- 9634728
TI - [In vivo diagnosis of Creutzfeldt-Jakob disease].
AB - The paper presents the data concerning usage of some original method of vital
laboratory diagnostics of Creutzfeldt-Jacob disease that belongs to the group of
prionic diseases. The method consisted in the inoculation of inoculative culture
of rat Gasser ganglion's neurinoma by biologic materials investigated (serum and
clot of blood) with the following passivation and investigation of the
contaminated culture by means of both morphologic and electron microscopic
methods. As an example of vital verificated case the wide pathomorphologic
analysis of the biopsy sample of brain was presented. Besides, the efficiency of
the investigation of cognitive evoked potentials (P300) together with EEG was
also demonstrated as the method of objectification of the development of dementia
in this disease.
PMID- 9634729
TI - [Clinical regularities in the relapsing and continuing course of phobic
disorders].
AB - To evaluate clinical regularities of the development of phobic disorders with
continuous and recurring course there were examined 67 patients with phobias. The
duration of disease was from 5 to 50 years. There were 3 variants of relapsing
and 4 variants of continuous course of phobic disorders taking into consideration
either presence or absence of the tendency to their progression. In the group of
relapsing patients 3% of the patients showed no tendency to progression. There
was also a relapsing variant with a tendency to progression (6.0%). Continuous
undulating without tendency to progression (8.9%), continuous-undulating with a
tendency to progression (19.4%), continuous-progressive (25.4%) and stationary
(28.4%) variants. The authors emphasize that revealed peculiarities in the
dynamics of phobic disorders with either presence or absence of the tendency to
progression may help to improve the therapy of such states and to make more
precise the prognosis of the disease.
PMID- 9634730
TI - [Psychotic and non-psychotic manifestations of alcoholism in forensic
psychiatry].
AB - The paper presents the results of examination of 110 alcoholic patients who have
committed criminal actions and were recognized as irresponsible at forensic
examination. It was established that wide spectrum of mental disorders were
present in such cases--from superacute psychotic states (15 patients) and acute
disorders (49) to chronic psychoses (33) and encephalopathy (13). According to
clinical manifestations mental disorders correspond in such cases to reactions of
exogenic type. In contrast to general medical departments where patients with
alcoholic delirium prevail, the studied sample of patients had primarily
psychoses with hallucinative-delirious and delirious disorders. Disorders of
personality manifested as typical alcoholic, asthenoneurotic, psychopathic-like,
residual-psychotic, psychoorganic changes and partial dementia (19 cases).
PMID- 9634731
TI - [Mental disorders in a pediatric clinic].
AB - In general pediatric clinic 262 children aged 1-15 years with functional
hyperthermia, functional disorders of cardiac rhythm (extrasystole, paroxysmal
and recurrent tachycardia), arterial hyper- and hypotension, autonomic
dysfunctions were examined. 21 children with organic cardiac diseases were
examined too. Mental disorders were revealed in all the cases: mono- and bipolar
affective disorders (58.1%) as well as affective-dilutional (10.4%) states,
primarily in the form of "masked" hypomanias, neurotic and neurotic-like (16.2%),
psychopathic and psychopathic-like (7.0%), psychoorganic (3.7%) and epileptiform
(4.6%) syndromes. The spectrum of mental disorders was extremely wide--from
practical normal (in limits of reactions of personal accentuations or age crisis)
to endogenic diseases. Combined treatment including drug therapy, psychotherapy
and family correction was quite effective.
PMID- 9634732
TI - [Principles of contemporary pharmacotherapy of insomnia].
PMID- 9634733
TI - [Correlation between functional activity of lymphocytes in patients with
Alzheimer's dementia and their response to therapy].
AB - 16 patients with dementia of Alzheimer's type (DAT) were examined. Functional
activity of lymphocytes was determined according to proliferating activity of T
lymphocytes, production of Interleukin-1 (IL-1) and estimation of subpopulations
of T-leukocytes (T-helpers, T-suppressors). The patients were observed both
before and 1-2.5 months after amiridin therapy. Considerable reduction of both IL
1 production and proliferating activity of T-lymphocytes was observed after the
treatment in 8 patients of 11. Their cognitive functioning after the therapy was
either improved or stable by the moment of repeated observation. It is quite
important that initial functional activity of lymphocytes was considerably higher
in this group of patients as compared with the age-matched controls. Change for
the worse in cognitive functions by the moment of the second examination was
accompanied in 5 patients with an increase in IL-1 production as compared to the
initial level. It is proposed that high level of IL-1 production by blood
lymphocytes may be used as a criterion in selection of DAT patients for amiridin
therapy.
PMID- 9634734
TI - [A familial case of mental retardation syndrome linked to fragile X chromosome].
PMID- 9634735
TI - [Adrenal insufficiency in nervous diseases].
PMID- 9634736
TI - [Restoration of vision in toxic damage of visual pathways: traditional treatment
combined with electrical stimulation].
PMID- 9634737
TI - [Cerebrovascular insufficiency in Takayasu arteritis].
PMID- 9634738
TI - [Various neurological aspects of critical care medicine].
PMID- 9634739
TI - [The dysfunction of nervous regulation in the genesis of immune disorders with
diseases of the nervous system].
PMID- 9634741
TI - [Commentary on the article by E.M. Burtsev and E.B. Maletskaia "Clinical aspects
and diagnostic criteria of benign intracranial hypertension in children" and
their review "Benign intracranial hypertension in children"].
PMID- 9634740
TI - [Evolutionary-biological conception of paraphilias].
PMID- 9634742
TI - Out with the old, in with the new: time for a new drug development agency?
PMID- 9634743
TI - BST off to a fast start, despite early stumbles.
PMID- 9634745
TI - Republican Congress could unsettle U.S. biotech.
PMID- 9634744
TI - The ethical roar of germ-line gene therapy.
PMID- 9634746
TI - Enzymatic 7-ADCA: I said it couldn't be done.
PMID- 9634747
TI - Comprehensive reform of the new drug regulatory process.
PMID- 9634748
TI - Suicide microbes on the loose.
PMID- 9634749
TI - Malarial epitopes expressed on the surface of recombinant tobacco mosaic virus.
AB - Using malaria as a model disease, we engineered the surface of tobacco mosaic
tobamovirus (TMV) for presentation of selected epitopes to the mammalian immune
system. The TMV coat protein is a well-characterized and abundant self-assembling
polymer previously shown to be a highly immunogenic carrier. Selected B-cell
epitopes were either inserted into the surface loop region of the TMV coat
protein or fused to the C terminus using the leaky stop signal derived from the
replicase protein reading frame. Tobacco plants systemically infected with each
of these constructs contained high titers of genetically stable recombinant
virus, enabling purification of the chimeric particles in high yield. Symptoms
induced in tobacco ranged from a normal mosaic pattern similar to that induced by
the parental U1 strain to a unique bright yellow mosaic. As measured by
quantitative ELISA against synthetic peptide standards, wild type TMV coat
protein and fusion protein synthesized by the leaky stop mechanism coassembled
into virus particles at the predicted ratio of approximately 20:1. Recombinant
plant viruses have the potential to meet the need for scalable and cost effective
production of subunit vaccines that can be easily stored and administered.
PMID- 9634750
TI - Production of cephalosporin intermediates by feeding adipic acid to recombinant
Penicillium chrysogenum strains expressing ring expansion activity.
AB - We demonstrate a novel and efficient bioprocess for production of the
cephalosporin intermediates, 7-aminocephalosporanic acid (7-ACA) or 7-amino
deacetoxycephalosporanic acid (7-ADCA). The Streptomyces clavuligerus expandase
gene or the Cephalosporium acremonium expandase-hydroxylase gene, with and
without the acetyltransferase gene, were expressed in a penicillin production
strain of Penicillium chrysogenum. Growth of these transformants in media
containing adipic acid as the side chain precursor resulted in efficient
production of cephalosporins having an adipyl side chain, proving that adipyl-6
APA is a substrate for either enzyme in vivo. Strains expressing expandase
produced adipyl-7-ADCA, whereas strains expressing expandase-hydroxylase produced
both adipyl-7-ADCA and adipyl-7-ADAC (aminodeacetylcephalosporanic acid). Strains
expressing expandase-hydroxylase and acetyltransferase produced adipyl-7-ADCA,
adipyl-7-ADAC and adipyl-7-ACA. The adipyl side chain of these cephalosporins was
easily removed with a Pseudomonas-derived amidase to yield the cephalosporin
intermediates.
PMID- 9634751
TI - Overproduction of encapsulated insecticidal crystal proteins in a Bacillus
thuringiensis spo0A mutant.
AB - The spo0A gene of Bacillus subtilis encodes the key factor involved in the
initiation of sporulation. It was previously shown that the B. thuringiensis (Bt)
cryIIIA gene, encoding a toxin active against coleopteran larvae, is
overexpressed in an spo0A mutant of B. subtilis. In this paper we describe the
construction of a Bt spo0A mutant strain and its use to produce insecticidal
crystal proteins. The spo0A gene of Bt was cloned and identified by its ability
to transform a B. subtilis spo0A mutant to prototrophy. Its nucleotide sequence
is homologous to the B. subtilis gene. The spo0A gene was replaced in the Bt
genome with a disrupted copy to give an Spo- strain unable to initiate
sporulation. When the cryIIIA gene was cloned in the Bt spo0A mutant, large
amounts of toxins were produced and accumulated to form a large crystal inclusion
which remained encapsulated within the ghost cell. These encapsulated toxins were
highly active against coleopteran larvae. We anticipate that the cryIIIA
expression system and the Bt spo0A mutant will provide a convenient process to
generate novel formulations of stabilized and environmentally safe Bt-based
biopesticides.
PMID- 9634752
TI - Plant seed oil-bodies as carriers for foreign proteins.
AB - Plant seeds frequently store oils (triglycerides) in discrete organelles called
oil-bodies. These are normally surrounded by a phospholipid half-unit membrane
equipped with specialized proteins called oleosins. Oleosins are highly
lipophilic proteins, are expressed at high levels in many seeds and are
specifically targeted to oil-bodies. We have investigated the potential of
oleosins to act as carriers for recombinant proteins by the production of
translational fusions between oleosins and genes encoding proteins foreign to
plant cells. We have shown that a fusion comprising a complete oleosin coding
domain and a beta-glucuronidase coding sequence may be expressed specifically in
the seeds of the oilseed crop plant, Brassica napus, and its product is correctly
targeted with approximately 80% of the activity partitioning with oil-bodies.
Recombinant oil-bodies may be used to facilitate separation of a recombinant
protein from other cellular proteins. Using this approach, the desired protein
may be cleaved from the oil-bodies using an endoprotease and further purified.
Alternatively, a fusion protein which is enzymatically active and resides on the
oil-bodies may be used directly in heterogeneous catalysis. In this application,
after a round of catalysis the oil-bodies may be recovered and re-used several
times without loss of activity. Thus the oil-bodies act as an immobilization
matrix. The fusion protein is stable in dry seeds for long periods and when
extracted has a half-life of 3-4 weeks on oil-bodies. Finally, the production of
these recombinant oil-bodies is extremely inexpensive, offering a novel route to
the manufacture of recombinant proteins.
PMID- 9634753
TI - Tumor suppressor genes: prospects for cancer therapies.
PMID- 9634754
TI - Production of polyhydroxyalkanoates, a family of biodegradable plastics and
elastomers, in bacteria and plants.
AB - In response to problems associated with plastic waste and its effect on the
environment, there has been considerable interest in the development and
production of biodegradable plastics. Polyhydroxyalkanoates (PHAs) are polyesters
that accumulate as inclusions in a wide variety of bacteria. These bacterial
polymers have properties ranging from stiff and brittle plastics to rubber-like
materials. Because of their inherent biodegradability, PHAs are regarded as an
attractive source of nonpolluting plastics and elastomers that can be used for
specialty and commodity products. The possibility of producing PHAs in large
scale and at a cost comparable to synthetic plastics has arisen from the
demonstration of PHA accumulation in transgenic Arabidopsis plants expressing the
bacterial PHA biosynthetic genes. Synergism between knowledge of the enzymes and
genes contributing to PHA synthesis in bacteria and engineering of plant
metabolic pathways will be necessary for the development of crop plants that
produce biodegradable plastics.
PMID- 9634755
TI - Red-shifted excitation mutants of the green fluorescent protein.
AB - Using optimized combinatorial mutagenesis techniques and Digital Imaging
Spectroscopy (DIS), we have isolated mutants of the cloned Aequorea victoria
green fluorescent protein (GFP) that show red-shifted excitation spectra similar
to that of Renilla reniformis GFP. Selective excitation of wild-type versus Red
Shifted GFP (RSGFP) enables spectral separation of these proteins. Six contiguous
codons spanning the tyrosine chromophore region were randomized and sequence
analysis of the mutants revealed a tyrosineglycine consensus. These mutants will
enable the simultaneous analysis of two promoters or proteins per cell or
organism. In consideration of the multitude of applications which are developing
for GFP alone, we envisage that spectrally shifted fluorescent proteins will be
of value to a diversity of research programs, including developmental and cell
biology, drug-screening, and diagnostic assays.
PMID- 9634756
TI - Engineered Fv fragments as a tool for the one-step purification of integral
multisubunit membrane protein complexes.
AB - The preparation of pure and homogeneous membrane proteins or membrane protein
complexes is time consuming, and the yields are frequently insufficient for
structural studies. To circumvent these problems we established an indirect
immunoaffinity chromatography method based on engineered Fv fragments. cDNAs
encoding the variable domains of hybridoma-derived antibodies raised against
various membrane proteins were cloned and expressed in Escherichia coli. The Fv
fragments were engineered to serve as bifunctional adaptor molecules. The Fv
fragment binds to the epitope of the membrane protein, while the Strep tag
affinity peptide, which was fused to the carboxy-terminus of the VH chain,
immobilizes the antigen-Fv complex on a streptavidin sepharose column. The
usefulness of this technique is illustrated with membrane protein complexes from
Paracoccus denitrificans, namely, the cytochrome c oxidase (EC 1.9.3.1), the
ubiquinol:cytochrome c oxidoreductase (EC 1.10.2.2), and subcomplexes or
individual subunits thereof. These membrane proteins were purified simply by
combining the crude P. denitrificans membrane preparation with the E. coli
periplasmic cell fraction containing the corresponding Fv fragment, followed by
solubilization and streptavidin affinity chromatography. Pure and highly active
membrane protein complexes were eluted in the Fv-bound form using diaminobiotin
for mild competitive displacement of the Strep tag. The affinity column could
thus be reused under continuous operation for several months. Five to 10 mg of
membrane protein complexes could be obtained without any detectable impurities
within five hours.
PMID- 9634757
TI - An allosteric hammerhead ribozyme.
AB - We have constructed an RNA molecule containing a hammerhead ribozyme that is
under allosteric control. In the inactive state, the RNA enzyme is unable to
cleave a suitable substrate. The formation of the active state of the ribozyme is
triggered by a specific interaction with a DNA oligonucleotide effector that is
complementary to a single-stranded loop in the RNA enzyme molecule. Other DNA or
RNA molecules containing unrelated nucleotide sequences do not function as
allosteric effectors. This work demonstrates the feasibility of designing RNA
enzymes that are specifically activated in response to an artificially designed
molecular recognition event. Such enzymes may have practical applications.
PMID- 9634758
TI - Binding epitope of somatostatin defined by phage-displayed peptide libraries.
AB - We have developed a versatile phagemid system to display peptides on the surface
of M13 bacteriophage at a copy number which approaches monovalency. In this
system, a phagemid encodes a peptide fused to the amino-terminus of the second
domain (dII) of the minor coat protein pIII under control of the inducible lac
promoter. The fusion protein is displayed in combination with several copies of
wild-type pIII on the surface of phage. Two diverse random octapeptide libraries,
one linear and one which contained flanking cysteines capable of forming
disulfide bridges, were were generated using an in vitro mutagenesis approach and
affinity selected on an anti-somatostatin mAb. Peptides with high affinity for
the mAb were enriched only from the cyclic library and the tetrapeptide, FWKT,
was identified by consensus as the binding epitope. The selected peptides
exhibited not only the primary amino acid sequence but also shared structural
features with somatostatin. One peptide, CRFWKTWC, also exhibited nanomolar
affinities for the five known somatostatin receptor subtypes. This system can
easily be adapted to display individual peptides or a wide range of custom
peptide libraries.
PMID- 9634759
TI - Recent advances in the large scale fermentation of Neisseria meningitidis group B
for the production of an outer membrane protein complex.
AB - The Outer Membrane Protein Complex (OMPC) of the bacterium Neisseria meningitidis
group B has been used successfully as a protein carrier in a Haemophilus
influenza type b (Hib) polysaccharide conjugate vaccine and a Streptococcus
pneumoniae (Pn) polysaccharide conjugate vaccine to elicit antipolysaccharide
immune responses in young infants. The OMPC carrier is derived by detergent
extraction of whole cells and, thus, the consistent generation of suitable
biomass is central to an effective production process. Therefore, we have
developed a large-scale, high-cell density (5 g/L dry cell weight) fermentation
process for the cultivation of N. meningitidis B11. Since current requirements
for the production of human biologics mandate strict control of all aspects of
the manufacturing process, several key features of the process, including a
chemically defined medium and a rational event-based harvest criterion, support
current good manufacturing practice (cGMP) and increased productivity.
PMID- 9634760
TI - Tight transcriptional control mechanism ensures stable high-level expression from
T7 promoter-based expression plasmids.
AB - One of the more efficient systems for high-level expression of cloned genes in
Escherichia coli makes use of a phage T7 late promoter whose activity depends on
a regulatable transcription unit supplying the specific T7 RNA polymerase. Using
various T7 RNA polymerase/T7 promoter-based vector host systems with differential
control on expression of the T7 RNA polymerase, we document that leaky expression
of the latter is responsible for the frequently observed loss of the culture's
ability to express genes of interest. We further show that the inability to
achieve detectable expression levels can be overcome by using a tightly repressed
expression system. We describe a novel and efficient control system in which
basal level expression of T7 RNA polymerase is attenuated by a series of tandemly
arranged transcription terminators. The plasmids also incorporate the phage
lambda-derived nutL/N protein antitermination function, allowing conditional
reversion of attenuation upon induction. The applicability of the system is
illustrated by the strictly regulatable, high-level production of several
cytokines of human and murine origin.
PMID- 9634761
TI - FDA advisory panel okays HIV vaccine.
PMID- 9634763
TI - Drug firms need biotech drug discovery.
PMID- 9634762
TI - Biotech plays big role in efforts against AIDS.
PMID- 9634764
TI - The vector void in gene therapy.
PMID- 9634765
TI - Virtual spectroscopy for fun and profit.
PMID- 9634767
TI - Generation of rabbit monoclonal antibody fragments from a combinatorial phage
display library and their production in the yeast Pichia pastoris.
AB - We have applied the combinatorial immunoglobulin library and phage display
technologies to generate monoclonal rabbit single-chain Fv (scFv) antibody
fragments specific for recombinant human leukemia inhibitory factor (rhLIF). The
B cell immunoglobulin repertoire of an immunized rabbit was immortalized by the
combinatorial cloning of the rearranged variable domains of light (VL) and heavy
(VH) chains. Affinity selection of the library displaying the rabbit antibody
domains on the phage surface resulted in the isolation of phage encoding scFv
antibodies which specifically bind to the antigen. We utilized the methylotrophic
yeast Pichia pastoris for high level secretion of soluble and functional scFv
antibody fragment. More than 100 mg/L of pure and functional rabbit anti-rhLIF
scFv antibody was obtained directly from the P. pastoris culture supernatant by
one-step affinity chromatography.
PMID- 9634768
TI - A hybrid baculovirus-bacteriophage T7 transient expression system.
AB - A hybrid recombinant baculovirus-bacteriophage T7 expression system was developed
for transient expression in insect cells of plasmids with foreign genes provided
with a T7 promoter. The coding sequence for T7 RNA polymerase, with or without a
nuclear localization signal, was inserted into the genome of Autographa
californica nuclear polyhedrosis virus. Recombinant viruses stably expressed T7
RNA polymerase in insect cells. Upon transfection of infected insect cells with
plasmids containing the genes for chloramphenicol acetyltransferase (CAT), the
hepatitis B virus precore-, core- or e- antigens under control of the T7
promoter, transient expression of these genes was detected by ELISA. The results
obtained indicate that this baculovirus/T7 system provides a simple and widely
applicable tool for transient gene expression studies.
PMID- 9634769
TI - Phage libraries displaying cyclic peptides with different ring sizes: ligand
specificities of the RGD-directed integrins.
AB - We have isolated selective ligands to the cell surface receptors of fibronectin
(alpha 5 beta 1 integrin), vitronectin (alpha v beta 3 and alpha v beta 5
integrins) and fibrinogen (alpha IIb beta 3 integrin) from phage libraries
expressing cyclic peptides. A mixture of libraries was used that express a series
of peptides flanked by a cysteine residue on each side (CX5C, CX6C, CX7C) or only
on one side (CX9) of the insert. A majority of the integrin-binding sequences
derived from the CX9 library contained another cysteine, indicating preferential
selection of conformationally constrained cyclic peptides. Each of the four
integrins studied primarily selected RGD-containing phage sequences but favored
different ring sizes and different flanking residues around the RGD motif. A
cyclic peptide ACRGDGWCG was synthesized based on a phage sequence that bound
particularly avidly to the alpha 5 beta 1 integrin. This peptide inhibited cell
attachment to fibronectin at about 5-fold lower concentrations than the most
potent cyclic peptides described earlier. The most interesting structure appeared
to contain two disulphide bonds. One such peptide, ACDCRGDCFCG, was synthetized
and shown to be at least 20-fold more potent inhibitor of alpha v beta 5- and
alpha v beta 3-mediated cell attachment to vitronectin than similar peptides with
a single disulphide bond and 200-fold more potent than commonly used linear RGD
peptides. These results emphasize the importance of conformational restriction as
a means of improving the potency of integrin-binding peptides and point to a new
way of designing effective peptides by resticting the peptide conformation with
more than one cyclizing bond.
PMID- 9634770
TI - A chromosome integration system for stable gene transfer into Thermus flavus.
AB - We have developed a chromosomal integration system for gene transfer into the
extreme thermophile Thermus flavus. The system relies on integration at the site
of leuB (3-isopropylmalate dehydrogenase) which was cloned from T. flavus. The
leuB gene was insertionally inactivated in vitro with a thermostable kanamycin
resistance gene and transformed in single-copy into the chromosome of T. flavus
on a plasmid vector. Gene replacement strains required leucine for growth, were
stably kanamycin-resistant and could grow in the presence of kanamycin at
temperatures up to 55 degrees C.
PMID- 9634771
TI - A computer program to determine a protein sequence from an amino acid analysis.
AB - We have developed a computational method for analyzing the proteolytic products
of a protein, knowing its sequence and the amino acid percentages of its
products. For all fragments, amino acid percentages are calculated and compared
to the experimental results (calculating the error within the experiment). The
program keeps the best fitted fragment using a least squared method. This program
was written to determine the sequence of the proteolytic products that appeared
during the purification of annexin I domain 2. The reliability of the method was
verified in this case. However the latter depends on the length and on the amino
acid composition of the entire protein and of its fragments. This program may be
suitable for analyzing the sequence of the products in any protease digestion,
whether designed or accidental.
PMID- 9634772
TI - For AIDS, the FDA may be reforming itself.
PMID- 9634773
TI - Group I introns: new molecular mechanisms for mRNA repair.
PMID- 9634774
TI - RNase P in research and therapy.
PMID- 9634775
TI - To treat or not to treat: that is the question for serum.
PMID- 9634776
TI - Combinatorial drug discovery: which methods will produce the greatest value?
AB - Combinatorial strategies are important new approaches to drug discovery, and it
seems quite likely that they will result in the discovery of interesting
potential pharmaceuticals. However, it is less clear whether combinatorial
approaches will result in quantum advances in therapeutics. Nor is there general
agreement about the factors most important in defining how combinatorial
strategies will provide value to the discovery of lead and therapeutic compounds.
In this review, we propose criteria that define the value of combinatorial
strategies and categorize the various approaches by: (a) the type of chemical
space to be searched, (b) the tactics employed to synthesize and screen
libraries, and (c) the structures of individual molecules in libraries. We
evaluate the strengths and weaknesses of the various strategies and suggest
milestones that can help to track their success.
PMID- 9634777
TI - Amplification of a chimeric Bacillus gene in chloroplasts leads to an
extraordinary level of an insecticidal protein in tobacco.
AB - The Bacillus thuringiensis (Bt) crystal toxins are safe biological insecticides,
but have short persistance and are poorly effective against pests that feed
inside plant tissues. Production of effective levels of these proteins in plants
has required resynthesis of the genes encoding them. We report that amplification
of an unmodified crylA(c) coding sequence in chloroplasts up to approximately
10,000 copies per cell resulted in the accumulation of an unprecedented 3-5% of
the soluble protein in tobacco leaves as protoxin. The plants were extremely
toxic to larvae of Heliothis virescens, Helicoverpa zea, and Spodoptera exigua.
Since the plastid transgenes are not transmitted by pollen, this report has
implications for containment of Bt genes in crop plants. Furthermore,
accumulation of insecticidal protein at a high level will facilitate improvement
in the management of Bt resistant insect populations.
PMID- 9634778
TI - Expression of thioredoxin random peptide libraries on the Escherichia coli cell
surface as functional fusions to flagellin: a system designed for exploring
protein-protein interactions.
AB - We have developed a system for probing protein/protein interactions which makes
use of the bacterial flagellum to display random peptide libraries on the surface
of E. coli. In developing the system the entire coding sequence of E. coli
thioredoxin (trxA) was inserted into a dispensable region of the gene for
flagellin (fliC), the major structural component of the E. coli flagellum. The
resulting fusion protein (FLITRX) was efficiently exported and assembled into
partially functional flagella on the bacterial cell surface. A diverse library of
random dodecapeptides were displayed in FLITRX on the exterior of E. coli as
conformationally constrained insertions into the thioredoxin active-site loop, a
location known to be a highly permissive site for the insertion of exogenous
peptide sequences into native thioredoxin. To demonstrate that members of this
library could be bound and selected via specific protein/protein interactions to
a target protein, a method was devised to enable efficient isolation of those
bacteria displaying peptides with affinity to immobilized antibodies. We have
unambiguously mapped three different antibody epitopes using this method.
Peptides selected as FLITRX active-site fusions retain their binding specificity
when made as native thioredoxin active-site loop fusions. This will facilitate
future structural characterizations and broaden the general utility of the system
for exploring other classes of protein-protein interactions.
PMID- 9634779
TI - Calmodulin as a versatile tag for antibody fragments.
AB - Calmodulin is a highly acidic protein (net charge -24 at pH 8.0 in the absence of
calcium) that binds to peptide and organic ligands with high affinity (Ka > 10(9)
M-1) in a calcium-dependent manner. We have exploited these properties to develop
calmodulin as a versatile tag for antibody fragments. Fusions of calmodulin with
single chain Fv fragments (scFv) could be expressed by secretion from bacteria in
good yield (5-15 mg/l in shaker flasks), and purified from periplasmic lysates or
broth to homogeneity in a single step, either by binding to anion-exchange resin
(DEAE-Sephadex), or to an organic ligand of calmodulin (N-(6-aminohexyl)-5-chloro
1-naphthalenesulfonamide-agarose). The antibody fusions could be detected by
binding of fluorescently labeled peptide ligands, as illustrated by their use in
confocal microscopy, fluorescent activated cell sorting and "band shift" gel
electrophoresis. Moreover, the interaction between calmodulin and peptide ligands
could provide a means of heterodimerization of proteins, as illustrated by the
assembly of an antibody-calmodulin fusion with maltose binding protein tagged
with a peptide ligand of calmodulin.
PMID- 9634780
TI - Surface expression and ligand-based selection of cDNAs fused to filamentous phage
gene VI.
AB - We describe a novel phage display system that affords the surface expression and
hence affinity selection of cDNAs. The strategy is based on a new approach to
functionally display proteins on filamentous phage through the attachment to the
C-terminus of the minor coat protein VI. The utility of the method was evaluated
using a cDNA library derived from the parasite Ancylostoma caninum. cDNA
sequences were fused in each of the three reading frames to the 3'-end of the M13
gene VI expressed by a phagemid vector. Phages rescued from this cDNA expression
library were subjected to biopanning against two serine proteases, trypsin and
the human coagulation factor Xa. This led to the identification of cDNAs encoding
novel members of two different families of serine protease inhibitors. The
authenticity of the cDNA selected with trypsin as the target was demonstrated by
purifying the encoded potent Kunitz-type inhibitor from an Ancylostoma caninum
extract. The rapid isolation of specific cDNAs with the protein VI monovalent
display system should facilitate the search for novel biologically important
ligands.
PMID- 9634781
TI - Phosphoric acid entrapment leads to apparent protein heterogeneity.
AB - Recombinant proteins produced in prokaryotes or eukaryotes show certain types of
heterogeneity due to post-translational modifications. Some preparations of a
soluble interferon gamma receptor, produced in Escherichia coli, appeared as a
double band with slightly different mobilities in non-reducing sodium
dodecylsulfate and native polyacrylamide gels. Ion spray mass spectrometry showed
that the two forms had a mass difference of one to three multiples of 97 +/- 2 D.
Gas chromatography-mass spectrometry analysis revealed the presence of phosphoric
acid in the hydrolysate and in the intact protein. The more slowly migrating
protein species had trapped molecules of phosphoric acid during the protein
extraction. Most of the trapped phosphoric acid was loosely associated with the
protein. One to three molecules were tightly, but non-covalently linked per
receptor molecule. Phosphoric acid entrapment did not affect biological activity
and most likely did not affect protein conformation. The species carrying
phosphoric acid showed higher solubility. Trapping of phosphoric acid by proteins
may be a general phenomenon and the results reported here thus useful in the
characterization of other recombinant proteins.
PMID- 9634782
TI - Production of recombinant proteins in Chinese hamster ovary cells using a protein
free cell culture medium.
AB - The growth-factor prototrophic Chinese hamster ovary (CHO) SSF3 cell line was
previously adapted for growth in serum-free media. Here we present a newly
designed medium which allows these cells to grow in the absence of any
exogenously added growth factors. To investigate the capacity of CHO SSF3 cells
for the efficient production of recombinant proteins in protein-free media,
expression plasmids containing either a human single chain urokinase-type
plasminogen activator (uPA)-encoding cDNA or a humanized immunoglobulin G (IgG)
kappa light chain cDNA were introduced by transfection. The tryptophan synthase
(trpB) gene of Escherichia coli was used as a dominantly acting selection marker
allowing the cells to survive in a medium containing indole in place of
tryptophan. Some of the clones obtained exhibited a stable uPA expression over a
period of several months under selective conditions and the yields were up to 74
mg of uPA/l in a bioreactor and the productivity was around 40 mg/day per 10(9)
cells. The yields of IgG light chains were up to 118 mg/l and the productivity
was in the order of 56 mg/day per 10(9) cells in a bioreactor. These results
demonstrate the potential of CHO SSF3 cells for the efficient production of
recombinant proteins under protein-free conditions.
PMID- 9634783
TI - Review of NIHRAC focuses on gene therapy.
PMID- 9634784
TI - Pharmacoeconomics: drug pricing's new guise.
PMID- 9634785
TI - The era of intracellular nucleic acid technology.
PMID- 9634786
TI - Clinical systems for the production of human cells and tissues.
PMID- 9634787
TI - Phytoremediation: a novel strategy for the removal of toxic metals from the
environment using plants.
AB - Toxic metal pollution of waters and soils is a major environmental problem, and
most conventional remediation approaches do not provide acceptable solutions. The
use of specially selected and engineered metal-accumulating plants for
environmental clean-up is an emerging technology called phytoremediation. Three
subsets of this technology are applicable to toxic metal remediation: (1)
Phytoextraction--the use of metal-accumulating plants to remove toxic metals from
soil; (2) Rhizofiltration--the use of plant roots to remove toxic metals from
polluted waters; and (3) Phytostabilization--the use of plants to eliminate the
bioavailability of toxic metals in soils. Biological mechanisms of toxic metal
uptake, translocation and resistance as well as strategies for improving
phytoremediation are also discussed.
PMID- 9634788
TI - Antibody VH domains as small recognition units.
AB - To develop immunoglobulin based recognition units of minimum size, a human heavy
chain variable domain (VH) was designed for selection of phage displayed VH. Non
specific binding of the VH through its interface for the light chain variable
domain (VL) was prevented through three mutations (G44E, L45R and W47G) in this
interface. These mutations were introduced to mimic camelid antibody heavy chains
naturally devoid of light chain partners. The third hypervariable loop of the
modified VH was then randomised to yield a repertoire of 2 x 10(8) independent
clones, which was displayed on phage and selected through antigen binding. VH
clones specific for hapten and protein antigens were isolated. Soluble VH was
expressed with an isoleucine residue at position 47 to improve expression and
stability compared to VH containing a glycine residue at this position, which
however was preferable for phage selection. Affinities of soluble VH for hapten
were between 100 nM and 400 nM. The VH domains were highly specific, stable and
well expressed in Escherichia coli. These positive biophysical properties and
their small size make them attractive for biotechnological applications.
PMID- 9634789
TI - Genetic transformation of banana and plantain (Musa spp.) via particle
bombardment.
AB - We have developed a simple protocol to allow the production of transgenic banana
plants. Foreign genes were delivered into embryogenic suspension cells using
accelerated particles coated with DNA. Bombardment parameters were optimized for
a modified particle gun resulting in high levels of transient expression of the
beta-glucuronidase gene in both banana and plantain cells. Bombarded banana cells
were selected with hygromycin and regenerated into plants. Molecular and
histochemical characterization of transformants revealed the stable integration
of the transferred genes into the banana genome.
PMID- 9634790
TI - Aggregation of a lyophilized pharmaceutical protein, recombinant human albumin:
effect of moisture and stabilization by excipients.
AB - In the presence of water vapor at 37 degrees C, lyophilized recombinant human
albumin (rHA) undergoes intermolecular thiol-disulfide interchange, eventually
forming high-molecular-weight, water-insoluble aggregates. The relationship
between the extent of aggregation and the water content of the lyophilized
protein was bell-shaped, with maximum aggregation (over 80% after one day) at
approximately 50 g water per 100 g dry protein, corresponding to incubation at
96% relative humidity. Nineteen different excipients were co-lyophilized with rHA
to test their ability to inhibit aggregation under these conditions. These
compounds included low- and high-molecular-weight sugars, as well as various
organic acids (amino, hydroxy, and aliphatic), and the simple inorganic salt
sodium chloride. Seven of them afforded complete stabilization of rHA against
moisture-induced aggregation. The stabilizing potency of the excipients
correlated with their water-sorbing capability, presumably due to increasing the
moisture level in the vicinity of rHA.
PMID- 9634791
TI - A system for production of commercial quantities of human lactoferrin: a broad
spectrum natural antibiotic.
AB - We previously reported the production of limited quantities of biologically
active recombinant human lactoferrin in the filamentous fungus Aspergillus
oryzae. In the present study, we report a modification of this production system
combined with a classical strain improvement program that has enabled production
of levels of recombinant human lactoferrin in excess of 2 g/l. The protein was
expressed in Aspergillus awamori as a glucoamylase fusion polypeptide which was
secreted into the growth medium and processed to mature human lactoferrin by an
endogenous KEX-2 peptidase. The recombinant protein retains full biological
activity in terms of its ability to bind iron and human enterocyte receptors.
Furthermore, the recombinant protein functions as a potent broad spectrum
antimicrobial protein.
PMID- 9634792
TI - Improved N-terminal processing of recombinant proteins synthesized in Escherichia
coli.
AB - Preparations of rHMfA (recombinant histone A from Methanothermus fervidus)
synthesized in E. coli by the heterologous expression of the hmfA gene were found
to contain a mixture of rHMfA molecules, approximately 40% that retained the N
terminal formyl-methionyl residue (f-met-rHMfA), approximately 50% that lacked
the formyl moiety but retained the methionyl residue (met-rHMfA), and only
approximately 10% that had lost both components of the protein synthesis
initiating amino acid residue and therefore had the same N-terminal sequence as
native HMfA molecules synthesized in Mt. fervidus. Expression of the hmfA gene in
E. coli cells grown in the presence of trimethoprim and thymidine, coupled with
the concurrent over-expression of a methionine aminopeptidase-encoding map gene,
has been shown to overcome this N-terminal heterogeneity problem and to result in
rHMfA preparations in which > 85% of the molecules have the fully processed,
native N-terminal sequence. This procedure should be generally useful for
ensuring N-terminal processing of recombinant proteins synthesized in E. coli.
PMID- 9634793
TI - Protease-dependent streptomycin sensitivity in E. coli--a system for protease
inhibitor selection.
AB - We have developed a bacterial cell system in which the activity of an expressed
heterologous protease confers a dominant streptomycin-sensitive (strs) phenotype
on the cell. This phenotype owes its high selectivity to the fact that
streptomycin (strep) resistance, which is conferred on E. coli by mutants of
ribosomal protein S12, is highly recessive to strep sensitivity. Thus, when strep
resistant (strr) strains of E. coli are transformed to co-express the wild-type
allele of S12 in addition to the mutant allele, their sensitivity to strep
increases by a factor of 100-1000. Similarly, we found that when the same strr
strains were transformed to co-express a heterologous protease and an inactive
fusion of S12 with a substrate of the protease, the strep sensitivity of the
cells increased approximately 100-fold. This effect was strictly dependent on
correct cleavage of the S12 precursor, required only modest levels of expression
of protease and substrate, and could be competitively inhibited by co-expression
of an alternative substrate gene. This system thus appears to be well-suited to
the identification of protease inhibitors, either by selection from libraries of
endogenously expressed random peptide-encoding genes, or by screening synthetic
or natural products libraries. Protease-dependent dominant phenotypes may be more
sensitive and appropriate than the more commonly used recessive phenotypes for
proteases which are activating enzymes.
PMID- 9634794
TI - Remodeling MMPIs.
PMID- 9634795
TI - Biomaterials in tissue engineering.
AB - Biomaterials play a pivotal role in field of tissue engineering. Biomimetic
synthetic polymers have been created to elicit specific cellular functions and to
direct cell-cell interactions both in implants that are initially cell-free,
which may serve as matrices to conduct tissue regeneration, and in implants to
support cell transplantation. Biomimetic approaches have been based on polymers
endowed with bioadhesive receptor-binding peptides and mono- and
oligosaccharides. These materials have been patterned in two- and three
dimensions to generate model multicellular tissue architectures, and this
approach may be useful in future efforts to generate complex organizations of
multiple cell types. Natural polymers have also played an important role in these
efforts, and recombinant polymers that combine the beneficial aspects of natural
polymers with many of the desirable features of synthetic polymers have been
designed and produced. Biomaterials have been employed to conduct and accelerate
otherwise naturally occurring phenomena, such as tissue regeneration in wound
healing in the otherwise healthy subject; to induce cellular responses that might
not be normally present, such as healing in a diseased subject or the generation
of a new vascular bed to receive a subsequent cell transplant; and to block
natural phenomena, such as the immune rejection of cell transplants from other
species or the transmission of growth factor signals that stimulate scar
formation. This review introduces the biomaterials and describes their
application in the engineering of new tissues and the manipulation of tissue
responses.
PMID- 9634796
TI - Transgenic canola and soybean seeds with increased lysine.
AB - We have increased the lysine content in the seeds of canola and soybean plants by
circumventing the normal feedback regulation of two enzymes of the biosynthetic
pathway, aspartokinase (AK) and dihydrodipicolinic acid synthase (DHDPS). Lysine
feedback-insensitive bacterial DHDPS and AK enzymes encoded by the
Corynebacterium dapA gene and a mutant E. coli lysC gene, respectively, were
linked to a chloroplast transit peptide and expressed from a seed-specific
promoter in transgenic canola and soybean seeds. Expression of Corynebacterium
DHDPS resulted in more than a 100-fold increase in the accumulation of free
lysine in the seeds of canola; total seed lysine content approximately doubled.
Expression of Corynebacterium DHDPS plus lysine-insensitive E. coli AK in soybean
transformants similarly caused several hundred-fold increases in free lysine and
increased total sed lysine content by as much as 5-fold. Accumulation of alpha
amino adipic acid (AA) in canola and saccharopine in soybean, which are
intermediates in lysine catabolism, was also observed.
PMID- 9634797
TI - Whole-virus vaccine development by continuous culture on a complementing host.
AB - We have evaluated an adaptive strategy for generating whole-virus vaccines using
a bacteriophage model. Wildtype phage T7 was cultivated in a two-stage continuous
stirred-tank reactor (CSTR) utilizing a recombinant E. coli host that
constitutively expressed T7 RNA polymerase, an essential enzyme of the early
viral metabolism. Over the course of 180 generations a diversity of phage
variants emerged, outgrew the wildtype, and were subsequently eclipsed by yet
fitter variants, based on host-ranges, restriction patterns, and one-step growth
responses of isolated clones. The fittest variant, which required complementation
by the recombinant host in order to grow, deleted at least 12 percent of its
genome and replicated twice as fast as the wildtype. Moreover, this variant was
immunogenically indistinguishable from the wildtype, based on cross-reactivities
of antisera raised against both. These results suggest the feasibility of the
proposed strategy for the development of safe whole-virus vaccines.
PMID- 9634798
TI - Expression of multiple eukaryotic genes from a single promoter in Nicotiana.
AB - We engineered an expression unit composed of three eukaryotic genes driven by a
single plant-active promoter and demonstrated functional expression in planta.
The individual genes were linked as translational fusions to produce a
polyprotein using spacer sequences encoding specific heptapeptide cleavage
recognition sites for NIa protease of tobacco vein mottling virus (TVMV). The NIa
gene itself was included as the second gene of the multi-gene unit. The first and
third genes, obtained from the TR region of pTi15955, encoded enzymatic functions
associated with the mannityl opine biosynthetic pathway. The mannityl opine
conjugase gene (mas2) was the first unit of the construct and provided the native
plant-active promoter and 5' untranslated regulatory sequence. The third gene
(mas1), encoding the mannityl opine reductase, furnished the native 3'
untranslated region. Cis-processing of the polyprotein by the NIa protease domain
was demonstrated in vitro using rabbit reticulocyte lysate and wheat germ cell
free translation systems. Tobacco plant cells transformed with the multi-gene
unit produced detectable levels of mannopine, mannopinic acid, and their
biosynthetic intermediates, deoxyfructosyl-glutamate and deoxyfructosyl
glutamine. This indicates that the polygene construct results in a set of
functional enzymatic activities that constitute a complete metabolic pathway.
PMID- 9634799
TI - N-glycosylation of recombinant human interferon-gamma produced in different
animal expression systems.
AB - Recombinant human interferon-gamma (IFN-gamma) was expressed in Chinese hamster
ovary cells, baculovirus-infected Sf9 insect cells and the mammary gland of
transgenic mice. The N-linked carbohydrate populations associated with both Asn25
and Asn97 glycosylation sites were characterized by matrix-assisted laser
desorption/ionization-mass spectrometry (MALDI-MS) in combination with
exoglycosidase array sequencing. A site-specific analysis of dual (2N) and single
(1N) site-occupancy variants of IFN-gamma derived from Chinese hamster ovary
cells showed that N-glycans were predominantly of the complex bi- and
triantennary type. Although Asn25-linked glycans were substituted with a core
fucose residue, Asn97 N-glycans were predominantly non-fucosylated, and truncated
complex and high-mannose oligosaccharide chains were also evident. Transgenic
mouse derived IFN-gamma exhibited considerable site-specific variation in N
glycan structures. Asn25-linked carbohydrates were of the complex, core
fucosylated type, Asn97-linked carbohydrates were mainly of the oligomannose
type, with smaller proportions of hybrid and complex N-glycans. Carbohydrates
associated with both glycosylation sites of IFN-gamma from Sf9 insect cells were
mainly tri-mannosyl core structures, with fucosylation confined to the Asn25
site. These data demonstrate the profound influence of host cell type and protein
structure on the N-glycosylation of recombinant proteins.
PMID- 9634800
TI - Improved adenovirus vector provides herpes simplex virus ribonucleotide reductase
R1 and R2 subunits very efficiently.
AB - We have constructed a new adenovirus (Ad) expression vector, pAdBM5, that allows
for the production of unprecedented levels of recombinant protein in the human
293 cell line using the Ad expression system. The main feature of this vector is
a combination of enhancer sequences that increases the activity of the ectopic
major late promoter (MLP) in recombinant Ad. In 293 cells infected with helper
free Ad recombinants generated with the pAdBM5 transfer vector, both herpes
simplex virus (HSV) ribonucleotide reductase R1 and R2 subunits represent the
most abundant polypeptides, accounting for as much as 15-20% of total cellular
proteins. Our data suggest that this level of expression is probably very close
to the upper limit of the system. Furthermore, when compared to the widely
utilized baculovirus (Bac)/Sf9 expression system, the improved Ad vector showed a
better performance for the production and purification of active HSV-2
ribonucleotide reductase R1 and R2 subunits. The R2 subunit was about 5-fold more
abundant in recombinant Ad-infected 293 cells than in Bac-infected Sf9 cells
while the R1 subunit was produced at roughly similar levels with either system.
However, the amount of active soluble R1 obtained from recombinant Ad-infected
293 cells was at least 5 times higher because most of the R1 produced in Sf9
cells was insoluble.
PMID- 9634801
TI - Structural and functional epitopes in the growth hormone receptor complex.
PMID- 9634802
TI - Extremozymes: expanding the limits of biocatalysis.
AB - The study of enzymes isolated from organisms inhabiting unconventional ecosystems
has led to the realization that biocatalysis need not be constrained to mild
conditions and can be considered at pH's, temperatures, pressures, ionic and
solvent environments long thought to be destructive to biomolecules. Parallel to
this, it has been demonstrated that even conventional enzymes will catalyze
reactions in solvents other than water. However, the intrinsic basis for
biological function under extreme conditions is only starting to be addressed, as
are associated applications. This was the focus of a recent NSF/NIST-sponsored
workshop on extremozymes. Given the information acquired from the study of
extremozymes, modification of enzymes to improve their ranges of stability and
activity remains a possibility. Ultimately, by expanding the range of conditions
suitable for enzyme function, new opportunities to use biocatalysis will be
created.
PMID- 9634803
TI - Directed evolution of a subtilisin with calcium-independent stability.
AB - Extracellular proteases of the subtilisin-class depend upon calcium for
stability. Calcium binding stabilizes these proteins in natural extracellular
environments, but is an Achilles' heel in industrial environments which contain
high concentrations of metal chelators. Here we direct the evolution of calcium
independent stability in subtilisin BPN'. By deleting the calcium binding loop
from subtilisin, we initially destabilize the protein but create the potential to
use new structural solutions for stabilization. Analysis of the structure and
stability of the loop-deleted prototype followed by directed mutagenesis and
selection for increased stability resulted in a subtilisin mutant with native
like proteolytic activity but 1000-times greater stability in strongly chelating
conditions.
PMID- 9634804
TI - Biological production of semisynthetic opiates using genetically engineered
bacteria.
AB - Semisynthetic derivatives of morphine and related alkaloids are in widespread
clinical use. Due to the complexity of these molecules, however, chemical
transformations are difficult to achieve in high yields. We recently identified
the powerful analgesic hydromorphone as an intermediate in the metabolism of
morphine by Pseudomonas putida M10. Here we describe the construction of
recombinant strains of Escherichia coli that express morphine dehydrogenase and
morphinone reductase. These strains are capable of efficiently transforming the
naturally occurring alkaloids morphine and codeine to hydromorphone and the
antitussive hydrocodone, respectively. Our results demonstrate the potential for
recombinant DNA technology to provide biological routes for the synthesis of
known and novel semisynthetic opiate drugs.
PMID- 9634805
TI - Polyclonal preparations of anti-tetanus toxoid antibodies derived from a
combinatorial library confer protection.
AB - We have compared the in vivo therapeutic potential of anti-tetanus toxin (TT)
human Fab antibodies derived from a combinatorial phage display library to
established polyclonal and monoclonal reagents. The oligoclonality and fine
specificity distribution of the synthetic anti-TT Fab preparations was comparable
to the antibody spectrum present in the donor serum and the affinities determined
for the synthetic phage-bound Fab (Phab) and soluble Fab were in the same range
as their monoclonal and polyclonal counterparts. On a weight basis, the
protective capacity of the new oligoclonal preparations in vivo (16.4 IU/100
micrograms Fab) was comparable to those of the best combinations of hybridoma
derived human monoclonal antibodies, and far better than those exhibited by the
polyclonal serum antibodies of the donor (0.29 IU/100 micrograms IgG) or by a
standard commercial human tetanus immunoglobulin preparation. These data suggest
that recombinant antibodies may become a safe and effective alternative to human
plasma-derived immunoglobulins for passive immunization.
PMID- 9634807
TI - Analyzing the science and ethics of xenografts.
PMID- 9634806
TI - Removal of sialic acid from a glycoprotein in CHO cell culture supernatant by
action of an extracellular CHO cell sialidase.
AB - We have directly tested the hypothesis that Chinese hamster ovary (CHO) cell
produced glycoproteins are subject to extracellular degradation by a sialidase
endogenous to the CHO cell line. Factors important to understanding the potential
for extracellular degradation are addressed including the glycoprotein
specificity, subcellular source, mechanism of release, and stability of the
sialidase activity. The extracellular CHO cell sialidase apparently originates
from the cytosol of the cells, and is released to the cell culture supernatant as
a result of damage to the cellular membrane. The extracellular sialidase is
active toward a variety of CHO cell-produced glycoproteins, and can hydrolyze
sialic acid from the recombinant glycoprotein gp120 in the culture supernatant.
While measuring the actual degradation of a glycoprotein by extracellular CHO
cell sialidase can be difficult, data presented here suggest that the level of
degradation can be estimated indirectly by using a more convenient fluorescent
substrate, 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid, to quantify
sialidase activity. Degradation by sialidase is minimized through addition of the
sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid to the culture
supernatant. The results in this study suggest additional potential approaches
for minimizing degradation by sialidase, including isolation of a sialidase
deficient CHO cell line.
PMID- 9634808
TI - Human IgA monoclonal antibodies specific for a major ragweed pollen antigen.
AB - Human hybridoma cell lines secreting IgG specific for the major allergen in the
pollen of short ragweed, Amb a I, were established from patients who had been
receiving antigen injections for immunotherapy. Recombinant Ig genes were then
constructed by cloning the heavy and light chain variable region genes of the
human hybridoma cell line and joining them to the human alpha or kappa constant
region genes in mammalian expression vectors. Amb a I-specific IgA was expressed
in two mouse myeloma cell lines, NS0 and Sp2/0. In both systems, transfected
alpha and kappa chains were assembled into IgA monomers or into dimers covalently
linked by the endogenous murine J chains. We propose that recombinant IgA
monoclonal antibodies specific for airborne allergens may be applied to the
mucosal surface of the nasal linings or of the lower airway of sensitized
individuals to inhibit the entry of allergenic molecules across the mucosal
epithelium and, therefore, to prevent the development of allergic responses.
PMID- 9634809
TI - Production of monoclonal antibodies using a secretion capture report web.
AB - We describe a novel method for the production of monoclonal antibodies using a
secretion capture report web (SCRW). Following HAT selection in bulk culture,
individual hybridomas are encapsulated in biotinylated agarose drops. Antibody
secreted by the hybridoma is captured within the agarose drop using an avidin
bridge and biotinylated anti-mouse immunoglobulin. The secreted antibody is
detected by a fluorescent reporter which can be either a second anti-mouse
antibody or an antigen. The binding of the reporter can be quantitated and the
desired hybridoma directly cloned by flow cytometry. Multiparameter (i.e., two
color) reporter analysis can also be used to selectively enrich and clone rare
hybridomas secreting antibodies directed to unique epitopes. The method allows
the characterization of thousands of clones per second and the isolation of
hundreds of clones per day.
PMID- 9634810
TI - Improved mimicry of a foot-and-mouth disease virus antigenic site by a viral
peptide displayed on beta-galactosidase surface.
AB - A major antigenic site (site A) of foot-and-mouth disease virus includes multiple
overlapping epitopes located within the flexible G-H loop of capsid protein VP1.
We have studied the antigenicity of several recombinant E. coli beta
galactosidases displaying the site A from a serotype C virus in different surface
regions of the bacterial enzyme. In each one of the explored insertion sites, the
recombinant peptide shows different specificity with a set of anti-virus
monoclonal antibodies directed to site A. In some of them, the inserted stretch
mimics better than free or haemocyanin-coupled peptide the antigenicity of site A
in the intact virus. In particular, an insertion within an exposed loop involved
in the activating interface of beta-galactosidase (amino acids 272 to 287) led to
a significant improvement of the overall reactivity. Since insertions at this
site renders proteins enzymatically active, the activating interface could be an
adequate place for the presentation of foreign antigens in correctly assembled
beta-galactosidase tetramers. These results also suggest that anti-virus
antibodies directed against the major antigenic site of FMDV recognize different
conformations of the G-H loop, which are better reproduced in some of the
recombinant proteins because of the dissimilar restrictions imposed by each
particular insertion site.
PMID- 9634811
TI - How will biotechnology fare in pharma's big plan?
PMID- 9634812
TI - Genomic sciences and the medicine of tomorrow.
PMID- 9634813
TI - What's in a name?
PMID- 9634814
TI - Gene knockout by viral delivery.
PMID- 9634815
TI - The 2',5' a antiviral system in plants: a dose of mammalian medicine.
PMID- 9634816
TI - Taking out Tat.
PMID- 9634817
TI - Trawling for proteins in the post-genome era.
PMID- 9634818
TI - Residue "switch" revealed in PTH system.
PMID- 9634819
TI - New treatments for acute stroke.
PMID- 9634820
TI - The extreme sensitivity of Mycobacterium tuberculosis to the front-line
antituberculosis drug isoniazid.
AB - Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolog of the
central regulator of peroxide stress response in enteric bacteria. Inactivation
of oxyR is specific for M. tuberculosis and other members of the M. tuberculosis
complex. This phenomenon appears as a paradox due to the ability of this organism
to parasitize host macrophages, in which the ingested organisms are likely to be
exposed to reactive oxygen intermediates. However, the surprising finding that M.
tuberculosis has multiple deletions, nonsense and frameshift mutations in oxyR
may help explain the exceptionally high sensitivity of M. tuberculosis to the
potent antituberculosis agent isoniazid. One of the genes affected by oxyR
lesions, ahpC (encoding an alkylhydroperoxide reductase) may determine the
intrinsic sensitivity of mycobacteria to isoniazid.
PMID- 9634821
TI - Sustained somatic gene inactivation by viral transfer of Cre recombinase.
AB - Transgenic and knockout mice have proven invaluable tools for analyzing
physiologically relavant functions of numerous genes. In some cases, however,
pleiotropic effects that result from a variable requirement for a particular gene
in different tissues, cell types, or stages of embryonic development may
complicate the analysis due to a complex phenotype or embryonic lethality. The
loxP/Cre-mediated recombination system, which allows tissue-specific gene
targeting in the mouse, can be used to overcome these problems. A limitation of
current methods is that a mouse carrying a loxP-tagged gene must be crossed with
a transgenic mouse expressing the Cre recombinase in an appropriate tissue to
obtain the desired gene rearrangement. We have used recombinant adenovirus
carrying the Cre recombinase to induce virtually quantitative somatic cell gene
disruption in the liver. The targeted gene was the multifunctional low-density
lipoprotein receptor-related protein (LRP), a cell surface receptor for alpha 2
macroglobulin and other ligands. Transient expression of Cre following adenoviral
infection produced the predicted gene rearrangement, functionally inactivating
LRP in the liver. Rearrangement occurred within 6 days after infection and
remained stable for at least 28 days. The results demonstrate the suitability of
adenoviral Cre gene transfer to induce long-term, quantitative, and temporally
controlled gene disruption in the mouse.
PMID- 9634822
TI - Virus-induced cell death in plants expressing the mammalian 2',5' oligoadenylate
system.
AB - The major components of the 2-5A system, responsible for the mammalian interferon
induced antiviral response, are the 2',5' oligoadenylate synthetase (2-5Aase) and
2',5' oligoadenylate (2-5A) dependent ribonuclease (RNase L). Transgenic tobacco
plants expressing these two enzyme activities were produced by crossing the
transgenic plants expressing RNase L with those expressing 2-5Aase. The double
transgenic plants showed complete resistance against cucumber mosaic virus (CMV),
infection with necrotic spots only forming on the virus-inoculated leaf. On the
other hand, although plants inoculated with potato virus Y (PVY) formed necrotic
spots on the inoculated leaf and virus amplification could not be detected, all
plants died within 20 days of inoculation. The transgenic tobacco plants
expressing either 2-5Aase or RNase L activity showed typical disease symptoms
with CMV- or PVY-inoculation. These results suggest that the introduced 2-5A
system is activated in tobacco cells by dsRNA, the replicating intermediates of
RNA viruses, leading to death of the host cells, which has not been observed in
mammalian cells.
PMID- 9634823
TI - Adenovirus targeted to heparan-containing receptors increases its gene delivery
efficiency to multiple cell types.
AB - Adenovirus (Ad) is used as a vector for gene delivery in therapies involving
genetic disease, vascular disease, and cancer. The first step for efficient gene
transfer is effective virus binding to the target cells. We have found that Ad
mediated gene delivery to multiple cell types is much less efficient compared to
epithelial-derived cells. Low gene delivery to nonepithelial cell types was
directly correlated to a deficiency of the cellular receptor which mediates Ad
binding. To overcome this inefficiency we constructed a new virus, AdPK, that
contains a heparin-binding domain that targets the virus to broadly expressed,
heparan-containing cellular receptors. AdPK delivers genes to multiple cell types
at markedly higher efficiencies than unmodified Ad. Viruses with enhanced
attachment characteristics significantly improve gene transfer efficiency and may
expand the tissues amenable to efficient Ad-mediated gene therapy.
PMID- 9634824
TI - Targeted gene delivery by tropism-modified adenoviral vectors.
AB - The utility of adenoviral vectors for gene therapy is currently limited due, in
part, to the widespread distribution of the cellular receptor for the adenovirus
fiber that precludes the targeting of specific cell types. In order to develop a
targeted adenovirus, it is therefore necessary both to ablate endogenous viral
tropism and to introduce novel tropism. We hypothesized that these two goals
could be achieved by employing a neutralizing anti-fiber antibody, or antibody
fragment, chemically conjugated to a cell-specific ligand. To test this concept,
we chose to target the folate receptor, which is overexpressed on the surface of
a variety of malignant cells. Therefore, we conjugated folate to the neutralizing
Fab fragment of an anti-fiber monoclonal antibody. This Fab-folate conjugate was
complexed with an adenoviral vector carrying the luciferase reporter gene and was
shown to redirect adenoviral infection of target cells via the folate receptor at
a high efficiency. Furthermore, when complexed with an adenoviral vector carrying
the gene for herpes simplex virus thymidine kinase, the Fab-folate conjugate
mediated the specific killing of cells that overexpress the folate receptor. This
work thus represents the first demonstration of the retargeting of a recombinant
adenoviral vector via a non-adenoviral cellular receptor.
PMID- 9634825
TI - Protein identification by solid phase microextraction-capillary zone
electrophoresis-microelectrospray-tandem mass spectrometry.
AB - We describe an analytical system for the rapid identification of proteins by
correlation of tandem mass spectra with protein sequence databases. The system
consists of an integrated solid phase microextraction/capillary zone
electrophoresis peptide separation device that is connected through a
microelectrospray ion source to a tandem mass spectrometer. The limits of
detection are 660 amol of sample at a concentration limit of < 33
amol/microliters for peptide mass measurement, and < 10 fmol of sample, at a
concentration limit of < 300 amol/microliters for peptide analysis by collision
induced dissociation. Using this system, we have identified low nanogram amounts
of yeast proteins separated by high-resolution two-dimensional gel
electrophoresis.
PMID- 9634826
TI - The rapid identification of intact microorganisms using mass spectrometry.
AB - Antibiotic-resistant strains of bacteria continue to emerge, increasing the need
for their fast and accurate identification. Matrix-assisted laser desorption
ionization time of flight mass spectrometry (MALDI-TOF-MS), has become a
prominent technique in biological mass spectrometry. We report the application of
MALDI-TOF-MS for the identification of intact Gram-negative and Gram-positive
microorganisms taken directly from culture. Analysis of bacteria from a single
colony is possible, allowing the screening of mixed cultures. Sample preparation
is simple and the analysis automated, providing spectra within minutes. The
spectra obtained allow identification of microorganisms from different genera,
different species, and from different strains of the same species. The procedure
provides a unique mass spectral fingerprint of the microorganism, produced from
desorbed components of the cell wall. Consistent data were obtained from
subcultures grown for 3-day and 6-day periods, from the same cultures 1 day later
and from fresh subcultures 2 months later.
PMID- 9634827
TI - Inactivation of MET10 in brewer's yeast specifically increases SO2 formation
during beer production.
AB - Sulfite is widely used as an antioxidant in food production. In beer brewing,
sulfite has the additional role of stabilizing the flavor by forming adducts with
aldehydes. Inadequate amounts of sulfite are sometimes produced by brewer's
yeasts, so means of controlling the sulfite production are desired. In
Saccharomyces yeasts, MET10 encodes a subunit of sulfite reductase. Partial or
full elimination of MET10 gene activity in a brewer's yeast resulted in increased
sulfite accumulation. Beer produced with such yeasts was quite satisfactory and
showed increased flavor stability.
PMID- 9634828
TI - Positive selection system to screen for inhibitors of human immunodeficiency
virus-1 transcription.
AB - We describe a transcription-based assay system to screen for antiviral drugs in
vivo. The system consists of two transcription units, a cytomegalovirus promoter
driving a reporter gene physically linked to an HIV-1 promoter oriented in the
opposite direction. Based on the arrangement of the transcription units, enhanced
HIV-1 promoter activity in the presence of the viral transactivating Tat protein
downregulates reporter gene expression initiated from the CMV promoter.
Inhibitors of HIV-1 transcription relieve the suppression and are identified by
an increase in reporter gene expression. This positive selection system allows
discrimination between drugs that nonspecifically block cellular functions by
cytotoxicity and molecules that specifically repress HIV-1 promoter activity.
PMID- 9634829
TI - Genetic engineering of potato for broad-spectrum protection against virus
infection.
AB - Transgenic potato plants expressing mutant alleles of PLRV ORF4, the gene for the
movement protein pr17 of this luteovirus, were generated for broad-range
protection against virus infection. When tested for protection against infection
by PLRV, all transgenic lines showed a significant reduction of virus antigen.
Potato lines accumulating N- or C-terminally extended PLRV pr17 mutant proteins
were resistant to infection by the unrelated potato viruses PVY and PVX.
Transgenic lines that did not express protein despite high transcript levels
failed to exhibit virus resistance.
PMID- 9634830
TI - Taking the hex off transgenic plant exports.
PMID- 9634831
TI - Why technology-based regulations don't work.
PMID- 9634832
TI - Measuring taxol production.
PMID- 9634833
TI - Taxol supply problem? What problem?
PMID- 9634834
TI - Gene of the month.
PMID- 9634835
TI - Genetic tests forge ahead, despite scientific concerns.
PMID- 9634836
TI - Nobel discovery in combinatorial chemistry.
PMID- 9634837
TI - US army to investigate "friendly fire" infections of Gulf war veterans.
PMID- 9634838
TI - Investors, HMOs, policy makers see value in vaccines.
PMID- 9634839
TI - Double standards in GMP deduplication row.
PMID- 9634840
TI - Sequence to array: probing the genome's secrets.
PMID- 9634841
TI - Intracerebral xenografts: Sertoli cells to the rescue?
PMID- 9634842
TI - Reengineering growth factors "through the looking glass".
PMID- 9634843
TI - Close encounters of the PNA kind.
PMID- 9634844
TI - Big news for plant transformation.
PMID- 9634845
TI - Metabolic engineering: the concept coalesces.
PMID- 9634846
TI - In vitro models for in vivo drug profiles.
PMID- 9634847
TI - Biotechnology consortia versus multifirm alliances: paradigm shift at work?
PMID- 9634848
TI - Bioregios put Germany on the biodevelopment map.
PMID- 9634849
TI - Scanning of nucleic acids by in vitro amplification: new developments and
applications.
AB - Nucleic acids can be characterized using a variety of "fingerprinting" techniques
usually based on nucleic acid hybridization or enzymatic amplification. The
scanning of nucleic acids by amplification with arbitrary oligonucleotide primers
has become popular because it can generate simple-to-complex patterns from
anonymous DNA or RNA templates without requiring prior knowledge of nucleic acid
sequence or cloned or characterized probes. Discrete loci are amplified within
genomic DNA, DNA complementary to mRNA populations (cDNA), cloned DNA fragments,
and even PCR products. The potential and limitations of the various genome
scanning techniques, novel improvements, and their recent use in comparative and
experimental biology applications, including the analysis of plant and bacterial
genomes are discussed.
PMID- 9634850
TI - Expression monitoring by hybridization to high-density oligonucleotide arrays.
AB - The human genome encodes approximately 100,000 different genes, and at least
partial sequence information for nearly all will be available soon. Sequence
information alone, however, is insufficient for a full understanding of gene
function, expression, regulation, and splice-site variation. Because cellular
processes are governed by the repertoire of expressed genes, and the levels and
timing of expression, it is important to have experimental tools for the direct
monitoring of large numbers of mRNAs in parallel. We have developed an approach
that is based on hybridization to small, high-density arrays containing tens of
thousands of synthetic oligonucleotides. The arrays are designed based on
sequence information alone and are synthesized in situ using a combination of
photolithography and oligonucleotide chemistry. RNAs present at a frequency of
1:300,000 are unambiguously detected, and detection is quantitative over more
than three orders of magnitude. This approach provides a way to use directly the
growing body of sequence information for highly parallel experimental
investigations. Because of the combinatorial nature of the chemistry and the
ability to synthesize small arrays containing hundreds of thousands of
specifically chosen oligonucleotides, the method is readily scalable to the
simultaneous monitoring of tens of thousands of genes.
PMID- 9634851
TI - A fiber-optic DNA biosensor microarray for the analysis of gene expression.
AB - A fiber-optic biosensor array is described for the simultaneous analysis of
multiple DNA sequences. A bundle of optical fibers was assembled with each fiber
carrying a different oligonucleotide probe immobilized on its distal end.
Hybridization of fluorescently labeled complementary oligonucleotides to the
array was monitored by observing the increase in fluorescence that accompanied
binding. The approach enables fast (< 10 min) and sensitive (10 nM) detection to
multiple DNA sequences simultaneously, with the potential for quantitative
hybridization analysis.
PMID- 9634852
TI - Cloning differentially expressed mRNAs.
AB - Differential gene expression occurs in the process of development, maintenance,
injury, and death of unicellular as well as complex organisms. Differentially
expressed genes are usually identified by comparing steady-state mRNA
concentrations. Electronic subtraction (ES), subtractive hybridization (SH), and
differential display (DD) are methods commonly used for this purpose. A rigorous
examination has been lacking and therefore quantitative aspects of these methods
remain speculative. We compare these methods by identifying a total of 58 unique
differentially expressed mRNAs within the same experimental system (HeLa cells
treated with interferon-gamma). ES yields digital, reusable data that quantitated
steady-state mRNA concentrations but only identified abundant mRNAs (seven were
identified), which represent a small fraction of the total number of
differentially expressed mRNAs. SH and DD identified abundant and rare mRNAs (33
and 23 unique mRNAs respectively) with redundancy. The redundancy is mRNA
abundance-dependent for SH and primer-dependent for DD. We conclude that DD is
the method of choice because it identifies mRNAs independent of prevalence, uses
small amounts of RNA, identifies increases and decreases of mRNA steady-state
levels simultaneously, and has rapid output.
PMID- 9634853
TI - Testis-derived Sertoli cells survive and provide localized immunoprotection for
xenografts in rat brain.
AB - Transplantation of neural tissue into the mammalian central nervous system has
become an alternative treatment for neurodegenerative disorders such as
Parkinson's disease. Logistical and ethical problems in the clinical use of human
fetal neural grafts as a source of dopamine for Parkinson's disease patients has
hastened a search for successful ways to use animal dopaminergic cells for human
transplantation. The present study demonstrates that transplanted testis-derived
Sertoli cells into adult rat brains survive. Furthermore, when cotransplanted
with bovine adrenal chromaffin cells (xenograft), Sertoli cells produce localized
immunoprotection, suppress microglial response and allow the bovine cells to
survive in the rat brain without continuous systemic immunosuppressive drugs.
These novel features support Sertoli cells as a viable graft source for
facilitating the use of xenotransplantation for Parkinson's disease and suggest
their use as facilitators, (i.e., localized immunosuppression) for cell
transplantation in general.
PMID- 9634854
TI - Engineering epidermal growth factor for enhanced mitogenic potency.
AB - Successful use of growth factors in therapeutic and bioprocessing applications
requires overcoming two attenuation mechanisms: growth factor depletion and
receptor down-regulation. Current ameliorative strategies use physiologically
inappropriate high growth-factor concentrations, along with periodic media
refeeding in vitro and reinjection or controlled-release devices in vivo. We
demonstrate a new approach derived from understanding how these attenuation
mechanisms arise from ligand/receptor trafficking processes. Specifically, a
recombinant epidermal growth factor (EGF) mutant with reduced receptor binding
affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or
transforming growth factor alpha because of its altered trafficking properties.
PMID- 9634855
TI - Enhancement of strand invasion by oligonucleotides through manipulation of
backbone charge.
AB - The ability of DNA oligonucleotides, neutral peptide nucleic acids (PNAS), and
oligonucleotide conjugates to hybridize to inverted repeat sequences within
supercoiled double-stranded DNA by Watson-Crick base-pairing is examined. PNAs
and oligonucleotide conjugates initiate and maintain strand invasion under more
stringent conditions than do unmodified DNA oligonucleotides. PNAs hybridize
rapidly and, once bound, hold open a target site allowing oligonucleotides to
base-pair to the displaced strand under conditions that would otherwise preclude
hybridization. The ability to manipulate hybridization efficiency through
different options for the alteration of oligomer charge should have important
implications for optimizing sequence-specific recognition of DNA.
PMID- 9634856
TI - Molecular mechanisms of biocatalytic desulfurization of fossil fuels.
AB - The development of biocatalytic desulfurization of petroleum fractions may allow
its use in place of conventional hydrodesulfurization (HDS). Dibenzothiophene
(DBT) is representative of a broad range of sulfur heterocycles found in
petroleum that are recalcitrant to desulfurization via HDS. Rhodococcus sp.
strain IGTS8 has the ability to convert DBT to 2-hydroxybiphenyl (HBP) with the
release of inorganic sulfur. The conversion of DBT to HBP is catalyzed by a
multienzyme pathway consisting of two monooxygenases and a desulfinase. The final
reaction catalyzed by the desulfinase appears to be the rate limiting step in the
pathway. Each of the enzymes has been purified to homogeneity and their kinetic
and physical properties studied. Neither monooxygenase has a tightly bound
cofactor and each requires an NADH-FMN oxidoreductase for activity. An NADH-FMN
oxidoreductase has been purified from Rhodococcus and is a protein of
approximately 25,000 molecular weight with no apparent sequence homology to any
other protein in the databases. We describe a unique sulfur acquisition system
that Rhodococcus uses to obtain sulfur from very stable heterocyclic molecules.
PMID- 9634858
TI - Open sandwich ELISA: a novel immunoassay based on the interchain interaction of
antibody variable region.
AB - We describe an immunoassay that is based on the interchain interaction of
separated VL and VH chains from a single chain antibody variable region. In the
presence of antigen, the chains reassociate. VL fragments of anti-hen egg
lysozyme (HEL) antibody HyHEL-10 were immobilized on microtiter plates. Samples
were coincubated with an M13-displayed VH chain, and assayed with peroxidase
labeled anti-M13 antibody. Signal was detected in direct proportion to the amount
of HEL in the sample. Wide dynamic range with < 15 ng/ml sensitivity was
attained.
PMID- 9634857
TI - Transdermal delivery of peptides by iontophoresis.
AB - Transdermal administration by iontophoresis (enhanced transport via the skin
using the driving force of an applied electric field) has been successfully
demonstrated but no formal relationship between peptide sequence/structure and
efficiency of delivery has been established. There are notable examples, such as
the lipophilic leutinizing hormone releasing hormone (LHRH) analogs, Nafarelin
and Leuprolide, that exhibit down-regulation of their own transport across the
skin under the influence of an iontophoretic current. The hypothesis that this
phenomenon is due to neutralization of the skin's net negative charge by these
cationic peptides was examined with LHRH oligopeptides. The impact of these
compounds on the electroosmotic flow of solvent into the skin, which is induced
by iontophoresis and which contributes significantly to the electrotransport of
large, positively charged ions, was examined and quantified. Close juxtaposition
of cationic and lipophilic residues profoundly inhibited electroosmosis and,
presumably, peptide flux. The results indicate that the lipophilicity of the
oligopeptides facilitates van der Waals interactions with hydrophobic patches
along the transport route, thereby permitting the positively charged oligopeptide
to interact with carboxylate side chains that give the skin its net negative
charge at neutral pH. The lipophilic, cationic oligopeptide, therefore, becomes
anchored in the transport path, neutralizing the original charge of the membrane,
and completely altering the permselective properties of the skin.
PMID- 9634859
TI - A clinician looks at the tearfilm.
PMID- 9634860
TI - Influence of gender, sex steroid hormones, and the hypothalamic-pituitary axis on
the structure and function of the lacrimal gland.
PMID- 9634861
TI - Androgen-regulated transcription in the epithelium of the rat lacrimal gland.
PMID- 9634862
TI - Gene cloning of BM180, a lacrimal gland enriched basement membrane protein with a
role in stimulated secretion.
AB - BM180 is a novel basement membrane component with a role in regulated tear
secretion by lacrimal acinar cells. BM180 bears some sequence similarity to alpha
gliadin, a plant protein against which antibodies have been reported in patients
with Sjogren's syndrome. A precedent for plantlike sequence in the mammalian
genome is provided by selectins, which possess a plant lectinlike domain involved
in inflammatory cell homing. Cloning the mouse and human BM180 gene will aid
molecular investigation of lacrimal acinar cell-BM180 interactions and may lead
to a new molecular understanding of mechanisms contributing to dry eye.
PMID- 9634863
TI - Sensory denervation leads to deregulated protein synthesis in the lacrimal gland.
PMID- 9634864
TI - Acinar cell basal-lateral membrane-endomembrane traffic may mediate interactions
with both T cells and B cells.
PMID- 9634865
TI - Tissue expression of tear lipocalin in humans.
PMID- 9634866
TI - The exorbital lacrimal glands of the rat are tensed in situ.
PMID- 9634867
TI - Aberrant lacrimal gland development in an anophthalmic mutant strain of rat.
PMID- 9634868
TI - Hormonal influences on Syrian hamster lacrimal gland. Marked repression of a
major 20 kDa secretory protein by estrogens, androgens, and thyroid hormones.
PMID- 9634869
TI - Androgen support of lacrimal gland function in the female rabbit.
PMID- 9634871
TI - Dinucleotide repeat polymorphism near the tear lipocalin gene.
PMID- 9634870
TI - Identification and hormonal control of sex steroid receptors in the eye.
PMID- 9634872
TI - Studies of ligand binding and CD analysis with apo- and holo-tear lipocalins.
PMID- 9634874
TI - Calcium signalling in lacrimal acinar cells.
PMID- 9634873
TI - Signal transduction pathways activated by cholinergic and alpha 1-adrenergic
agonists in the lacrimal gland.
PMID- 9634875
TI - Voltage- and Ca(2+)-dependent chloride current activated by hyposmotic and
hyperosmotic stress in rabbit superior lacrimal acinar cells.
PMID- 9634876
TI - G protein coupling of receptor activation to lacrimal secretion.
PMID- 9634877
TI - Microtubules and intracellular traffic of secretory proteins in rat extraorbital
lacrimal glands.
PMID- 9634878
TI - Effects of neuropeptides on serotonin release and protein and peroxidase
secretion in the isolated rat lacrimal gland.
PMID- 9634879
TI - Analysis of phosphodiesterase isoenzymes in the ocular glands of the rabbit.
PMID- 9634880
TI - Immunohistochemistry and secretory effects of leucine enkephalin in the isolated
pig lacrimal gland.
PMID- 9634881
TI - Interaction between vasoactive intestinal polypeptide (VIP) and neuropeptide Y
(NPY) in the isolated rat lacrimal gland.
PMID- 9634882
TI - Identification and cellular localization of the components of the VIP signaling
pathway in the lacrimal gland.
PMID- 9634883
TI - Kinesin activation drives the retrieval of secretory membranes following
secretion in rabbit lacrimal acinar cells.
PMID- 9634884
TI - Protein kinase C isoforms differentially control lacrimal gland functions.
PMID- 9634885
TI - Role of protein kinases in regulation of apical secretion and basal-lateral
membrane recycling traffic in reconstituted rabbit lacrimal gland acini.
PMID- 9634886
TI - Brefeldin A detoxification in rat extraorbital lacrimal glands.
PMID- 9634887
TI - Identification and characterization of G proteins in the mammalian lacrimal
gland.
PMID- 9634888
TI - Inward-rectifying potassium channels in the rabbit superior lacrimal gland.
PMID- 9634889
TI - Electrophysiological evidence for reduced water flow from lacrimal gland acinar
epithelium of NZB/NFW F1 mice.
PMID- 9634890
TI - Cellular origin of mucins of the ocular surface tear film.
AB - In summary, we have demonstrated that the ocular surface epithelia express at
least three mucin genes. We suggest that the gel-forming mucin MUC5AC is a major
mucin forming the mucus gel of the tear film. We further suggest that MUC1
facilitates the spread of the MUC5-containing mucus on the ocular surface and,
along with the mucus gel, prevents cell and debris adhesion to the ocular
surface. The function of MUC4 at the ocular surface remains to be elucidated.
PMID- 9634891
TI - Soluble mucin and the physical properties of tears.
PMID- 9634892
TI - Characterization and origin of major high-molecular-weight tear
sialoglycoproteins.
PMID- 9634893
TI - Detection and quantification of conjunctival mucins.
PMID- 9634894
TI - Mucous contribution to rat tear-film thickness measured with a microelectrode
technique.
PMID- 9634895
TI - Structural analysis of secreted ocular mucins in canine dry eye.
PMID- 9634896
TI - Corneal epithelial tight junctions and the localization of surface mucin.
PMID- 9634897
TI - Breakup and dewetting of the corneal mucus layer. An update.
PMID- 9634898
TI - The meibomian glands and tear film lipids. Structure, function, and control.
AB - Meibomian gland disease--and, in particular, obstructive meibomian gland disease-
makes an important contribution to ocular surface disease, in the form of
meibomian keratoconjunctivitis. With improved methods for the study of meibomian
oil composition and function, we are moving closer to the possibility of
distinguishing the contribution of meibomian deficiency, as opposed to
inflammatory events, to this disorder. More importantly, where aqueous tear
deficiency and meibomian gland disease coincide in patients with dry eye, we are
closer to the possibility of distinguishing their relative contributions to the
dry eye state. This has implications for future therapies.
PMID- 9634899
TI - Tear film interferometry as a diagnostic tool for evaluating normal and dry-eye
tear film.
PMID- 9634900
TI - Human and rabbit lipid layer and interference pattern observations.
PMID- 9634901
TI - Abnormal lipid layers. Observation, differential diagnosis, and classification.
PMID- 9634902
TI - Association of tear lipid layer interference patterns with superficial punctate
keratopathy.
PMID- 9634903
TI - Meibomian secretions in chronic blepharitis.
PMID- 9634904
TI - Androgen regulation of the meibomian gland.
PMID- 9634905
TI - Delivery of meibomian oil using the Clinical Meibometer.
PMID- 9634906
TI - Volume of the human and rabbit meibomian gland system.
PMID- 9634907
TI - Effect of meibomian gland occlusion on tear film lipid layer thickness.
PMID- 9634908
TI - Meibomian gland lipids, evaporation, and tear film stability.
PMID- 9634909
TI - Surface-chemical pathways of the tear film breakup. Does corneal mucus have a
role?
PMID- 9634910
TI - The biophysical role in tear regulation.
PMID- 9634911
TI - Longitudinal analysis of precorneal tear film rupture patterns.
PMID- 9634912
TI - The role of tear proteins in tear film stability in the dry eye patient and in
the rabbit.
PMID- 9634913
TI - Relationship between pre-ocular tear film structure and stability.
PMID- 9634914
TI - Association of precorneal and preconjunctival tear film.
PMID- 9634915
TI - Age and gender effects on the normal tear film.
PMID- 9634916
TI - The kinetics of lid motion and its effects on the tear film.
PMID- 9634917
TI - Hydrodynamics of meniscus-induced thinning of the tear film.
PMID- 9634918
TI - Computer-assisted calculation of exposed area of the human eye.
PMID- 9634919
TI - Cytokines. An overview.
PMID- 9634921
TI - Apoptosis in the lacrimal gland and conjunctiva of dry eye dogs.
PMID- 9634920
TI - Gender- and androgen-related impact on the expression of proto-oncogenes and
apoptotic factors in lacrimal and salivary glands of mouse models of Sjogren's
syndrome.
PMID- 9634922
TI - Cytokines and tear function in ocular surface disease.
AB - In summary, tear EGF levels correlate most strongly with tear production in
normals, and it is likely that some form of homeostatic mechanism exists to
provide a constant supply to the ocular surface. Commercial ELISA kits appear to
measure EGF in tears with good consistency and may be useful in the future to
improve comparability of data from different studies. In addition, in ocular
rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there
is a differential increase in the level of the inflammatory cytokine IL-1 alpha
in the tear fluid. Much of this elevation appears to be the result of reduced
tear turnover, which may form an important positive feedback mechanism
encouraging tear stagnation and the perpetuation of ocular surface inflammation.
PMID- 9634924
TI - Molecular basis and role of differential cytokine production in T helper cell
subsets in immunologic disease.
PMID- 9634923
TI - Chemokine production in conjunctival epithelial cells.
PMID- 9634925
TI - Presence and testosterone influence on the levels of anti- and pro-inflammatory
cytokines in lacrimal tissues of a mouse model of Sjogren's syndrome.
PMID- 9634927
TI - Do cytokines have a role in the regulation of lacrimal gland acinar cell ion
transport and protein secretion?
AB - The present study explored the potential involvement of cytokines (IL-1 alpha, IL
1 beta, IL-6, and IFN-gamma) in the regulation of basic physiological processes
carried out by lacrimal acinar cells. Overall, evidence gathered supports the
hypothesis that cytokines may be involved in the regulation of lacrimal secretory
processes. When combined with earlier studies, these data suggest that acute
treatment (i.e., 20 min) of acinar cells with cytokines does not significantly
impact either basal or carbachol-stimulated ion transport or protein secretion.
However, chronic treatment of cultured acinar cells with cytokines does appear,
in some instances, to influence these cell functions. For example, 24 h treatment
of acinar cells with IL-6 or IFN-gamma did not alter basal or carbachol
stimulated protein (beta-hexosaminidase) secretion, whereas a combination of IL-1
alpha and IL-1 beta decreased carbachol-stimulated beta-hexosaminidase secretion
by 80%. The mechanism behind this effect is unknown, but it appears to stem from
an increase in the basal secretion rather than a decrease in the stimulated
secretion. Future studies will attempt to identify the mechanism behind the
actions of IL-1 alpha and IL-1 beta, in addition to testing other pertinent
cytokines (e.g., TNF-alpha, TGF-beta). The study of cytokine involvement in the
regulation of lacrimal acinar cell physiology has received relatively little
attention. Thus, substantial gaps remain concerning the identity of cytokines,
their source(s) and interplay, receptor distribution, second messenger
involvement, and ultimate influence over the secretion of aqueous tears.
PMID- 9634926
TI - Infiltrating lymphocyte populations and cytokine production in the salivary and
lacrimal glands of autoimmune NOD mice.
PMID- 9634928
TI - The rat exorbital lacrimal gland as a site of synthesis of EGF-like growth
factors.
PMID- 9634929
TI - The distribution of FGF-2 and TGF-beta within the lacrimal gland of rabbits.
PMID- 9634931
TI - Time course of apoptosis in lacrimal gland after rabbit ovariectomy.
PMID- 9634930
TI - Tear fluid changes after photorefractive keratectomy.
PMID- 9634932
TI - Co-expression of bcl-2 and CD44s in basal layers of human ocular surface
epithelia.
PMID- 9634933
TI - Alterations of ocular surface gene expression in Sjogren's syndrome.
AB - We have demonstrated that conjunctival epithelium of SS patients displays
increased numbers of S-phase cells compared with non-dry eye controls. Moreover,
in SS patients, these S-phase cells are distributed throughout all strata of the
epithelium. The expression of MUC-1, a cell surface marker indicative of
terminally differentiated epithelium, is localized to the conjunctival epithelial
surface in SS and control patients. However, MUC-1 surface immunoreactivity
appears to be reduced in SS epithelium, suggesting disruption of normal
epithelial differentiation. A MUC-1 epitope exposed by pretreatment with
neuraminidase is expressed in the basal and suprabasal layers of both patient
populations. This antigen likely represents nascent, partially processed MUC-1(6)
and may serve as a marker of the preterminally differentiated epithelial
phenotype. Messenger RNA encoding several different inflammatory cytokines,
including TNF-alpha, IL-1 alpha and beta, IL-6, IL-8, IL-10, and TGF-beta 1, is
expressed at elevated levels within the conjunctival epithelium of SS patients
compared with non-dry eye controls. Based on these observations, we have
formulated a model to explain the ocular surface pathology of Sjogren's syndrome.
We hypothesize that mechanical abrasion secondary to aqueous tear deficiency
creates an inflammatory environment where conjunctival epithelial cells and
lymphocytes are stimulated to produce and secrete various cytokines (i.e., IL-1,
TNF-alpha, IL-6, IL-8, etc.) into the tear film. Elevated cytokine levels within
the tear film, perhaps combined with reduced concentrations of essential lacrimal
gland-derived factors (i.e., EGF, retinol), create an environment in which
terminal differentiation of the ocular surface epithelium is impaired. As a
consequence, the epithelium becomes hyperplastic, displaying increased mitotic
activity, and loses the ability to express mature protective surface molecules
including the membrane-bound mucin, MUC-1. This would imply that anti
inflammatory medications (i.e., corticosteroids or cyclosporine) that suppress
the inflammatory component of this cascade may ameliorate the ocular surface
disease and discomfort experienced by SS patients.
PMID- 9634934
TI - Growth factor interaction with contact lenses: evidence for and possible effects
of storage of basic FGF in contact lenses. Preliminary results.
PMID- 9634935
TI - Neural, endocrine, and immune system interactions. Relevance for health and
disease.
PMID- 9634936
TI - Inductive sites for rat tear IgA antibody responses.
PMID- 9634937
TI - Anatomy of mammalian conjunctival lymphoepithelium.
AB - Ocular surface immune mechanisms are subservient to the fine function of the eye.
A clear cornea with a smooth, well-lubricated facade is prerequisite to lucid
vision. Hence, corneal inflammation and post-inflammatory scarring are
intolerable, and the cornea contains a minimum of lymphoid elements. Although
conjunctival dysfunction and consequent tear film deficiency can malign the
corneal surface, conjunctival inflammation is tolerated to a considerable degree.
In contrast to the human cornea, human conjunctiva contains an abundance of
lymphoid tissue. Certain aspects of human conjunctival immunology elicit little
debate. Langerhans cells are abundant in conjunctival epithelium. Isolated CD8+
suppressor/cytotoxic T cells predominate in conjunctival epithelium, while T
cells in the substantia propria distribute equally between CD4+ T helper cells
and CD8+ cells. Yet the presence of plasma cells in human conjunctiva, the
expression of secretory component by human conjunctival epithelium, and the
function of human conjunctival lymphoid follicles are in dispute. Confusion may
derive in part from the use of inappropriate animal models; rodent conjunctiva
does not appear to be a worthy facsimile for human conjunctiva. Discrepancies
between different human studies likely result from variance in subject age,
biopsy site and extent, histologic or histochemical technique, and perhaps the
degree of inflammation present at the time of biopsy. Careful immunohistochemical
and in situ molecular assays on well-defined loci within the conjunctiva of
comparable human subjects may resolve such questions in the future. Organized
mucosa-associated lymphoid tissue is rigorously defined as mucosal lymphoid
follicles with an ultrastructurally distinct overlying lymphoepithelium. Based on
available evidence, the epithelium overlying mammalian conjunctival lymphoid
follicles does not contain distinct M cells. Whether zonal differences in
morphology reflect real differences in the capacity to sample tear film antigens
for presentation to the mucosal immune system remains to be established.
PMID- 9634938
TI - Binding of a cytopathic or an invasive strain of P. aeruginosa to cytoskeletal,
basement membrane, or matrix proteins of wounded cornea is similar and does not
rely on interaction with actin filaments.
PMID- 9634939
TI - Secretory IgA responses on the human ocular surface.
PMID- 9634940
TI - A method to study induction of autoimmunity in vitro: co-culture of lacrimal
cells and autologous immune system cells.
AB - Co-culturing autologous lacrimal gland cells and immune system cells can lead to
spleen cell proliferation with a time course similar to that for proliferation in
a typical heterologous MLR. Although these results are consistent with the
hypothesis that lacrimal acinar cells are a source of antigen, and may or may not
serve in part as an APC, future studies of this preparation are required to test
these hypotheses. We are unaware of reports demonstrating that co-culturing
control epithelial tissue and autologous splenic lymphocytes from apparently
healthy animals leads to lymphocytic proliferation. Our results suggest that the
appropriate co-culture of tissues and immune cells from healthy animals, perhaps
such as detailed above, should help identify mechanisms contributing to the
induction of autoimmune disease. Knowledge regarding such mechanisms should help
efforts to prevent such disease, and perhaps reverse it.
PMID- 9634941
TI - Rat lacrimal glands contain activated and resting mature T cells, recent thymic
emigrants, and possibly extrathymic populations.
PMID- 9634942
TI - Immunohistochemical examination of lacrimal gland tissue from patients with
ocular sarcoidosis.
PMID- 9634943
TI - Immunoglobulin levels in the tears of patients with corneal grafts and transplant
rejection.
PMID- 9634944
TI - Tear fluid influence on the ocular surface.
PMID- 9634945
TI - Effects of lacrimal gland removal on squirrel monkey cornea.
PMID- 9634946
TI - Lacrimal gland growth factors and receptors: lacrimal fibroblastic cells are a
source of tear HGF.
PMID- 9634947
TI - Clusterin may be essential for maintaining ocular surface epithelium as a non
keratinizing epithelium.
PMID- 9634948
TI - Effects of chronic hypertonic stress on regulatory volume increase and Na-K-2Cl
cotransporter expression in cultured corneal epithelial cells.
PMID- 9634949
TI - A unified theory of the role of the ocular surface in dry eye.
AB - It is our belief that the pathology of dry eye occurs when systemic androgen
levels fall below the threshold necessary for support of secretory function and
generation of an anti-inflammatory environment (Fig. 3). When this occurs, both
the lacrimal gland and the ocular surface become irritated and inflamed, and they
secrete cytokines that interfere with the normal neural connections that drive
the tearing reflex. This leaves the lacrimal gland in an isolated condition,
perhaps exacerbating atrophic alterations of the glandular tissue. These changes
allow for antigen presentation at the surface of the lacrimal acinar cells and
increase lymphocytic infiltration of the gland. A similar series of events may be
occurring on the ocular surface. From this hypothesis we conclude: 1. The ocular
surface, lacrimal gland, and interconnecting innervation act as an integrated
servo-mechanism. 2. Once the lacrimal gland loses its androgen support, it is
subject to immune/neurally mediated dysfunction. 3. The ocular surface is an
appropriate target for dry eye therapeutics.
PMID- 9634950
TI - Human tear film components bind Pseudomonas aeruginosa.
PMID- 9634951
TI - Small-volume analysis of rabbit tears and effects of a corneal wound on tear
protein spectra.
PMID- 9634952
TI - 31-27 kDa caseinolytic protease in human tears.
PMID- 9634953
TI - Tear protein levels following punctal plugging.
PMID- 9634954
TI - Characterization of cells shed from the ocular surface in normal eyes.
PMID- 9634955
TI - Healing effect of sodium-sucrose-octasulfate and EGF on epithelial corneal
abrasions in rabbits.
PMID- 9634956
TI - A novel approach to resolve cellular volume responses to an anisotonic challenge.
PMID- 9634957
TI - Classification of artificial tears. I: Composition and properties.
PMID- 9634958
TI - Classification of artificial tears. II: Additives and commercial formulas.
PMID- 9634959
TI - The ocular surface, the tear film, and the wettability of contact lenses.
PMID- 9634960
TI - Conjunctival permeability and ultrastructure. Effects of benzalkonium chloride
and artificial tears.
PMID- 9634961
TI - Preservative effect on epithelial barrier function measured with a novel
technique.
PMID- 9634962
TI - Video biomicroscopy of the tear film.
PMID- 9634963
TI - Patient-dependent and material-dependent factors in contact lens deposition
processes.
PMID- 9634964
TI - Effectiveness of BION tears, Cellufresh, Aquasite, and Refresh Plus for moderate
to severe dry eye.
PMID- 9634965
TI - Ocular residence time of carboxymethylcellulose solutions.
PMID- 9634966
TI - Vitronectin adsorption in contact lens surfaces during wear. Locus and
significance.
PMID- 9634967
TI - Effect of tears and tear residues on worn etafilcon and polymacon disposable
contact lenses on the adhesion of Pseudomonas aeruginosa.
PMID- 9634968
TI - Hyaluronan in dry eye and contact lens wearers.
PMID- 9634969
TI - Epidemiology and classification of dry eye.
PMID- 9634970
TI - CANDEES. The Canadian Dry Eye Epidemiology Study.
PMID- 9634971
TI - Sensitivity and specificity of a screening questionnaire for dry eye.
AB - We developed a Dry Eye Screening Questionnaire for the Dry Eye Epidemiology
Projects (DEEP), a proposed large epidemiologic study. All persons who screen
positive and a small sample of those who screen negative are to be invited for a
diagnostic examination. Containing 19 questions, of which only 14 were used in
the analysis, the questionnaire takes only a few minutes to administer on the
telephone. To construct a discriminator function and thus a ROC curve, we used
stepwise multiple regression on screening responses from a clinic series of 77
cases and 79 controls. Stepwise regression may incorporate into the predictor
equation variables whose relation to the predicted is only accidental. Further,
misclassification rates are underestimated by the resubstitution method, in which
the proportion misclassified is obtained from the same dataset in which the
discriminator function was fitted. To counter these problems, we randomly divided
the data in half. We chose as predictors only those variables (Dry and Irritated)
selected by stepwise regression in both data halves. We estimated unbiased
misclassification rates using the unbiased test set method, in which the
discriminator is fitted in one data half, and misclassification rates are
calculated in the other half. Comparison of ROC curves arising from
resubstitution and test set estimates indicates that resubstitution bias in
misclassification rate estimation is negligible in our data. A resubstitution
estimate made on the entire data is thus preferred. The resulting
sensitivity/specificity values are reasonably high (e.g., 60%/94%), suggesting
that the questionnaire will be a useful screening tool in the DEEP study. A
second discriminator using the sum of all 14 responses is similar in its
misclassification characteristics to the first discriminator. A second
potentially significant error, arising from applying results from a clinical
series to a general population, will be investigated as survey results in DEEP
become available.
PMID- 9634972
TI - Use of a questionnaire for the diagnosis of tear film-related ocular surface
disease.
PMID- 9634973
TI - Importance of conjunctival epithelial evaluation in the diagnostic
differentiation of dry eye from drug-induced epithelial keratopathy.
PMID- 9634974
TI - The size of corneal epithelial cells collected by contact lens cytology from dry
eyes.
PMID- 9634975
TI - Optimum dry eye classification using questionnaire responses.
PMID- 9634976
TI - Diagnostic value of tear film abnormalities in a new syndrome affecting the
neuroendocrine and immune systems.
PMID- 9634977
TI - Low-tech detection of tear film-related diseases of the ocular surface.
PMID- 9634978
TI - Using LIPCOF (lid-parallel conjunctival fold) for assessing the degree of dry
eye, it is essential to observe the exact position of that specific fold.
PMID- 9634979
TI - Use of the Tearscope Plus and attachments in the routine examination of the
marginal dry eye contact lens patient.
PMID- 9634980
TI - Evaluation of Schirmer tests by two types of tear clearance tests.
PMID- 9634981
TI - Fluorescein dye concentration as a factor in tear film fluorescence.
PMID- 9634982
TI - A new method for measuring human basic tear fluid osmolality.
PMID- 9634983
TI - Micropachometric quantification of tear assessment tests.
AB - After reviewing the results of available methods for defining the dry eye with an
exact assessment of severity, we found that micropachometry was the most
sensitive. The following is a ranking of the other tests according to usefulness:
Tear resistance, Schirmer, and BUT. Rose bengal stained eyes were usually
decompensated; the meniscus test's primary use was as an "all or nothing"
indicator, but recording the widths of extant menisci were unproductive.
PMID- 9634984
TI - Use of corneal thickness changes to compare the efficacy of conventional eye
drops with supracutaneous treatment of dry eye.
PMID- 9634985
TI - Sjogren's syndrome. Pathogenesis and new approaches to therapy.
PMID- 9634986
TI - Reflex tearing in dry eye not associated with Sjogren's syndrome.
PMID- 9634987
TI - Cytokine mRNA expression in labial salivary glands and cytokine secretion in
parotid saliva in Sjogren's syndrome.
PMID- 9634988
TI - Age-related decrease in innervation density of the lacrimal gland in mouse models
of Sjogren's syndrome.
PMID- 9634989
TI - Aberrant expression and potential function for parotid secretory protein (PSP) in
the NOD (non-obese diabetic) mouse.
PMID- 9634990
TI - Survey of canine tear deficiency in veterinary practice.
PMID- 9634991
TI - Lacrimation and salivation are not related to lymphocytic infiltration in
lacrimal and salivary glands in MRL lpr/lpr mice.
PMID- 9634992
TI - The Sjogren syndrome and tear function profile.
PMID- 9634993
TI - Cytokines may prove useful in the treatment of Sjogrens syndrome (SS) dry eye.
PMID- 9634994
TI - The now and future therapy of the non-Sjogren's dry eye.
PMID- 9634995
TI - Dry eye treatment with eye drops that stimulate mucin production.
PMID- 9634996
TI - A dose-ranging clinical trial to assess the safety and efficacy of cyclosporine
ophthalmic emulsion in patients with keratoconjunctivitis sicca. The Cyclosporine
Study Group.
PMID- 9634997
TI - Oral pilocarpine for symptomatic relief of dry mouth and dry eyes in patients
with Sjogrens syndrome.
PMID- 9634998
TI - Oral pilocarpine for symptomatic relief of keratoconjunctivitis sicca in patients
with Sjogren's syndrome. The MGI PHARMA Sjogren's Syndrome Study Group.
PMID- 9634999
TI - Supracutaneous treatment of dry eye patients with calcium carbonate.
PMID- 9635000
TI - Preclinical safety studies of cyclosporine ophthalmic emulsion.
PMID- 9635001
TI - Conjunctival impression cytology from dogs with keratoconjunctivitis sicca. Pre-
and post-treatment with topical cyclosporine.
PMID- 9635002
TI - Cyclosporine distribution into the conjunctiva, cornea, lacrimal gland, and
systemic blood following topical dosing of cyclosporine to rabbit, dog, and human
eyes.
PMID- 9635003
TI - Estrogen therapy in keratoconjunctivitis sicca.
PMID- 9635004
TI - Dry eye treatment with acupuncture. A prospective, randomized, double-masked
study.
PMID- 9635005
TI - Punctal occlusion for the treatment of dry eye.
PMID- 9635006
TI - Keratoprosthesis in pemphigoid and Stevens-Johnson syndrome.
AB - Keratoprosthesis was implanted in 17 eyes with ocular pemphigoid and 7 eyes with
Stevens-Johnson syndrome and followed for 6 months to 6 years. Visual outcomes
and complications were compared. Pemphigoid was found to have a much better
prognosis than did Stevens-Johnson syndrome. Keratoprosthesis is now firmly
indicated in elderly pemphigoid patients whose vision in both eyes has become
reduced to hand movements or less due to a corneal opacity.
PMID- 9635007
TI - Portable device for programmable, automatic, or on-demand delivery of artificial
tears.
PMID- 9635008
TI - Hypotaurine oxidation: an HPLC-mass approach.
PMID- 9635009
TI - In vitro evaluation of hypotaurine activity on oxidized LDL.
PMID- 9635010
TI - Hypotaurine protection on cell damage by H2O2 and on protein oxidation by Cu+2
and H2O2.
PMID- 9635011
TI - Cysteine sulfinate decarboxylase (CSD): molecular cloning, sequence and genomic
expression in brain.
PMID- 9635012
TI - Effect of taurine and guanidinoethane sulfonate on glutathione metabolism in the
rat.
PMID- 9635013
TI - Determination of cysteinyl-containing peptides and associated enzyme activities
in rat tissues by reverse phase HPLC.
PMID- 9635014
TI - The effects of aging on taurine content and biosynthesis in different strains of
rats.
PMID- 9635015
TI - Taurine levels and localization in pancreatic islets.
PMID- 9635016
TI - Pyrrolizidine alkaloid-induced depletion of taurine from rat liver in vivo and in
vitro.
PMID- 9635017
TI - Effects of taurine in precision-cut liver slices exposed to the pyrrolizidine
alkaloid retrorsine.
PMID- 9635018
TI - Effect of taurine on biliary metabolites of glutathione in liver perfused with
the pyrrolizidine alkaloid, monocrotaline.
PMID- 9635019
TI - Antagonism by taurine on the ruthenium red-induced and 6-hydroxydopamine plus 1
methyl-4-phenylpyridinium-induced Ca2+ release from rat liver mitochondria.
PMID- 9635020
TI - Effect of taurine supplementation on the lipid peroxide formation and the
activities of glutathione-related enzymes in the liver and islet of type I and II
diabetic model mice.
AB - Effects of taurine supplementation on lipid peroxide formation and the activities
of glutathione (GSH) dependent enzymes in diabetic model mice were investigated.
Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type
II diabetes mellitus was produced by high calorie diet feeding to genetically
hyperglycemic KK mice. Taurine was given in drinking water at the level of 5%
(w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of
type I diabetes were significantly increased compared to the control group but
the levels were significantly decreased by taurine supplementation. In the type
II diabetic model, the concentrations of MDA were not changed by taurine
treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased
in the type I diabetic group, but in type II animals it was decreased. Hepatic
GPX activity of both type I and II diabetics was not altered by taurine
supplementation but was increased in the islets of the type II animals. No effect
on the activity of GSH S-transferase (GST) was observed in both types of diabetes
(I and II) following taurine supplementation. These results suggest that taurine
supplementation protects type I diabetic mice from lipid peroxide formation.
PMID- 9635022
TI - Effect of taurine on excitation-contraction coupling of extensor digitorum longus
muscle of dystrophic mdx mouse.
PMID- 9635021
TI - Taurine protects the liver against lipid peroxidation and membrane disintegration
during rat hepatocarcinogenesis.
AB - The purpose of this study was to determine the effects of taurine supplementation
on both hepatic morphological changes and the extent of hepatic lipid
peroxidation and membrane disintegration during rat hepatocarcinogenesis. Sprague
Dawley rats were fed high fat diets containing 15% corn oil and were maintained
on drinking water with or without 1% taurine. Two weeks after the appropriate
feeding regimen, hepatocarcinogenesis was induced by a modification of the Solt
and Farber method. This involved a 8 week protocol, including diethylnitrosamine
initiation, 3 weeks of 2-acetylaminofluorene feeding and finally a 70% partial
hepatectomy. Morphological changes of the hepatocyte were observed by
transmission electron microscopy (TEM). Hepatocytes of the carcinogen-treated rat
not exposed to taurine contained normal nuclei, but the endoplasmic reticulum
(ER) and the mitochondria (Mi) were almost destroyed. By contrast, although the
hepatocytes from the taurine supplemented group contained some irregular contour
nuclei, the ER and Mi were normal. In the carcinogen-treated groups, lipid
peroxidation was decreased because of the activation of several detoxifying
enzymes. Glutathione S-transferase (GST) activity increased in the carcinogen
treated groups but less so in the group supplemented with taurine before
treatment with the carcinogen. In the group supplemented with taurine prior to
treatment with the carcinogen, glutathione peroxidase (GPx) activity was higher
than in the carcinogen-treated group lacking taurine exposure. Consistent with
the severe destruction to the membrane in the carcinogen-treated rats, hepatic
glucose-6-phosphatase (G6Pase) activity, an index of membrane stability, was also
decreased. However, both the fall in G6Pase activity and the degree of membrane
damage was reduced in the carcinogen-treated animals receiving oral taurine.
These results suggest that taurine appears to inhibit lipid peroxidation, to
alter the activity of the defense enzymes and to protect the liver against
membrane disintegration during rat hepatocarcinogenesis.
PMID- 9635023
TI - Cardiac actions of taurine as a modulator of the ion channels.
AB - During ischemia, hypoxia and cardiac failure, the heart undergoes several adverse
changes, including a reduction in taurine (2-aminoethanesulfonic acid). Oral
administration of taurine under these disease conditions would be expected to act
like a mild cardiac glycoside. Taurine would exert improvement in the
accumulation of [Na]i and the loss of alpha-amino acids. Nonetheless, when
intracellular taurine content is raised, there would be the benefit of increased
Ca2+ release from the sarcoplasmic reticulum and increased Ca2+ sensitivity of
the contractile proteins, as well as possible changes in the action potential
associated with the actions of taurine on ion channels. In fact, intracellular
application of taurine produces the opposite actions to extracellularly
administration of the amino acid. From our previous experiments, the
electrophysiological actions of taurine on cardiac muscle cells include the
following. (a) Prolongation of action potential duration (APD) at high [Ca]i and
shortening of APD at low [Ca]i. In multicellular preparations, however, taurine
did not always prevent [Ca]o-induced effects. (b) Stimulation of spontaneous
activity at low intracellular and extracellular Ca2+ concentrations ([Ca]i and
[Ca]o), and vice versa. (c) Inhibition of the L-type Ca2+ current (ICa(L)) at
high [Ca]i, and vice versa. (d) Enhancement of the T-type Ca2+ current (ICa(T)).
(e) Inhibition of fast Na+ current (INa). (f) Enhancement of TTX-insensitive slow
Na+ current. (g) Inhibition of delayed rectifier K+ current (IKrec) at high
[Ca]i, and vice versa. (h) Enhancement of the transient outward current (Ito).
(i) Inhibition of the ATP-sensitive K+ current (IK(ATP)). Since taurine acts on
so many ion channels and transporters, it is clearly non-specific. Although it is
very difficult to understand the diversity of taurine's actions, it is possible
that taurine can exert its potent cardioprotective actions under the conditions
of low [Ca]i, as well as Ca2+ overload. Thus, although taurine-induced modulation
of ion channels located on the cardiac cell membrane is complex, the multiple
effects may combine to yield useful therapeutic results.
PMID- 9635024
TI - Taurine improves angiotensin II-induced hypertrophy of cultured neonatal rat
heart cells.
AB - The effect of taurine on angiotensin II-induced hypertrophy of cultured neonatal
rat heart cells (myocytes and nonmyocytes) was examined. Angiotensin II (1-100
nM) alone caused an increase in the rate of protein synthesis and the surface
area of myocytes without altering the rate of DNA synthesis or cell number. It
also mediated an increase in DNA synthesis and in cell number of nonmyocytes.
Exposure of the cells to taurine (20 mM) in the absence of angiotensin II had no
effect on either hyperplastic growth or hypertrophy of the two types of cultured
cardiac cells. However, myocytes pretreated with 20 mM taurine exhibited reduced
responsiveness to angiotensin II. Following a 24 hr pretreatment with 20 mM
taurine, the stimulation in protein synthesis by angiotensin II (1 nM) was
significantly suppressed. Similarly, taurine treatment of nonmyocytes reduced the
degree of angiotensin II-induced promotion of hyperplastic growth (DNA synthesis
and cell number). Finally, taurine partially prevented the rise in [Ca2+]i
mediated by angiotensin II in cardiac cells. The present results indicate that
taurine is an effective inhibitor of angiotensin II action. The possibility that
the beneficial effects of taurine in the treatment of heart failure might be
related to its suppression of angiotensin II-mediated cellular responses is
discussed.
PMID- 9635025
TI - Effects of taurine on signal transduction steps induced during hypertrophy of rat
heart myocytes.
AB - Angiotensin II plays an important role in the development of cardiac hypertrophy.
One factor thought to contribute to the trophic activity of angiotensin II in
fibroblasts is the elevation in [Ca2+]i. Although this theory has received
considerable support in cardiac fibroblasts, it is much more controversial in
cardiac myocytes. Therefore, the aim of this report was to examine the effect of
several Ca2+ modulators on protein synthesis in neonatal cardiac myocytes. We
found that angiotensin II increased both [Ca2+]i and the rate of protein
synthesis in isolated myocytes. Both effects were blocked by nifedipine, but only
the angiotensin II-mediated increase in [Ca2+]i was inhibited by taurine in a
dose-dependent manner. These data support the notion that Ca2+ plays only a
permissive role in angiotensin II-mediated stimulation of protein synthesis. By
contrast, the ability of taurine to attenuate the positive chronotropic effect,
the prolongation of the action potential and the proarrhythmic activity of
angiotensin II appear to be linked directly to changes in [Ca2+]i. We conclude
that taurine reverses these actions of angiotensin II by altering Ca2+ flux
across the cell membrane.
PMID- 9635026
TI - Effect of taurine depletion on angiotensin II-mediated modulation of myocardial
function.
AB - Taurine depletion was induced by either incubation of isolated myocytes with 5 mM
beta-alanine or feeding rats with water containing 3% beta-alanine. Hearts of
taurine depleted rats exhibited an impairment in myocardial relaxation,
associated with a decrease in Na(+)-Ca2+ exchanger activity. Exposure of the
heart to angiotensin II, an activator of the Na(+)-Ca2+ exchanger, eliminated the
relaxation defect. In agreement with the contractile results, taurine depletion
prolonged the calcium transient, an effect which was partially eliminated by
exposure to angiotensin II. Although peak systolic [Ca2+]i was modestly depressed
in the taurine depleted myocyte, peak ventricular pressure was normal. This may
be related to an elevation in pHi induced by taurine depletion. Angiotensin II
had little effect on contractility of the taurine depleted heart, presumably
because of two opposing effects, a reduction in pHi and an increase in [Ca2+]i.
Thus, taurine depletion alters contractile function and ion transport and both of
these effects are modulated by exposure of the heart to angiotensin II.
PMID- 9635027
TI - Taurine inhibition of iron-stimulated catecholamine oxidation.
PMID- 9635029
TI - Uptake of taurine and taurine chloramine in murine macrophages and their
distribution in mice with experimental inflammation.
PMID- 9635028
TI - Effects of taurine supplementation on lipid peroxidation, blood glucose and blood
lipid metabolism in streptozotocin-induced diabetic rats.
AB - The purpose of this study was to determine the effect of taurine on several
complications of diabetes, including oxidative stress, glucose intolerance and
blood lipid profile. Sprague Dawley male rats were fed an experimental diet for 7
weeks, at which time they were maintained on drinking water with or without 1%
taurine. The experimental period was 7 weeks and the rats were administered
streptozotocin (STZ) to induce diabetes. Thiobarbituric acid reactive substances
(TBARS) content was increased following the STZ injection, but was lowered by
prior treatment with taurine. The primary diabetic symptoms, such as polydipsia
and polyuria, were ameliorated in rats supplemented with taurine before the STZ
injection. Plasma triglyceride (TG) levels of the diabetic group were decreased
by taurine supplementation, although plasma total cholesterol (T-chol) and HDL
cholesterol (HDL-chol) were not different among the groups. LDL cholesterol (LDL
chol) levels of the control group were significantly decreased by taurine
supplementation, however, the time of taurine administration affected the
response of the diabetic group; only diabetic rats treated with taurine after the
administration of STZ showed a decrease in LDL cholesterol. Therefore, taurine
inhibits lipid peroxidation and decreases blood TG and LDL-chol levels, however,
the time and dose of taurine supplementation are variables that need to be
considered in the treatment of diabetes.
PMID- 9635030
TI - Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in
activated human polymorphonuclear leukocytes.
PMID- 9635031
TI - Myeloperoxidase (MPO) may mediate neutrophil adherence to the endothelium through
upregulation of CD11B expression--an effect downregulated by taurine.
AB - Extracellular myeloperoxidase (MPO) is a macrophage modulator which stimulates
release of the pro-inflammatory cytokine TNF alpha in addition to reactive oxygen
species (ROS) generated by these cells. MPO-induced macrophage secretion of pro
inflammatory mediators indirectly upregulates neutrophil pro-inflammatory
capacity through contributing to neutrophil priming for respiratory burst
activity. However, to date the question concerning a direct influence on the
neutrophil by MPO or the MPO-derived product hypochlorous acid (HOCl) remains to
be elucidated. Taurine, the most abundant free amino acid in human neutrophils
acts as an antioxidant through the formation of taurine-chloramine by
sequestering HOCl. Zinc also has antioxidant properties and taurine-zinc
complexes have been shown to have greater efficacy than either agent alone in
protection against ROS-mediated tissue damage. The aims of this study were: (a)
to determine if extracellular MPO modulates the inflammatory response through
autocrine feedback on the neutrophil and to investigate if taurine either
directly or indirectly through taurine-chloramine formation may further influence
this pathway and (b) to evaluate the efficacy of a taurine-zinc combination in
modulating MPO-induced CD11b receptor expression.
PMID- 9635032
TI - No beneficial effects of taurine application on oxygen free radical production
after hemorrhagic shock in rats.
AB - Oxygen free radical generation contributes to the reinfusion damage after
hemorrhagic shock. Taurine has been proposed to have radical scavenging
properties under certain experimental conditions. Therefore the present study was
undertaken to investigate if taurine would be able to attenuate adverse effects
of shock/resuscitation in male rats (fasted over night). Under pentobarbital
anesthesia, hemorrhagic shock (HS) was induced for 1 h by bleeding of the animal
[mean arterial blood pressure (MAP) = 40 mm Hg] followed by shed blood reinfusion
and another 1 h period of resuscitation. Rats were divided into two groups:
Treated rats (n = 6) were injected with taurine (40 mg/kg body mass) prior to
withdrawal of shed blood; untreated rats (n = 9) received respective volumes of a
normal saline solution. In untreated animals, free radical induced lipid
peroxidation was documented by an increase of malondialdehyde (MDA) in the
systemic circulation (nmol/ml; HPLC measurement) from 1.06 +/- 0.08 during
normotension (NT) to 1.35+/- 0.18** 1 h after resuscitation (RS). Accordingly,
plasma levels of alanine aminotransferase (ALT) (11 +/- 2; 35 +/- 12; 94 +/- 44
U/l, NT; HS; RS) and ammonia (120 +/- 39; 532 +/- 161; 224 +/- 101 micrograms/dl)
changed significantly during the experimental protocol. Hepatic ATPase-content as
an indicator of energetic status of the liver fell from 4.8 +/- 0.83 to 0.56 +/-
0.27 after HS and recovered to only 2.7 +/- 1.6 mumol/g after RS. Leukocyte
infiltration of the liver was followed by tissue levels of myeloperoxidase (MPO)
which did not change during HS, but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4;
77.5 +/- 24; arbitrary units), documenting an inflammatory reaction after HS.
Taurine treated rats showed levels of MDA not different from untreated rats after
RS; also no differences were observed concerning enzyme concentrations and
ammonia levels. The liver tissue levels of ATP and MPO revealed no differences
between the two groups during the various periods of the experiment. Liver tissue
perfusion, as measured by Laser Doppler flowmetry, also did not show significant
differences between both groups. MAP was significantly higher in the taurine
treated rats during the first 40 min of resuscitation. It is concluded that even
a relatively high dose of taurine failed to attenuate the impact of oxygen free
radicals and did not improve the recovery of the rats during the early
resuscitation period.
PMID- 9635033
TI - Influence of taurine supplementation on ischemic preservation of the isolated rat
kidney.
PMID- 9635034
TI - Taurine: an osmolyte in mammalian tissues.
PMID- 9635035
TI - Phospholemman: a cardiac taurine channel involved in regulation of cell volume.
PMID- 9635037
TI - Adaptations of cerebral volume-regulatory taurine transport to chronic
disturbances of plasma osmolality.
PMID- 9635036
TI - Taurine efflux and intracellular pH during astrocyte volume regulation.
AB - Cytotoxic cerebral edema is characterized by enlarged astroglial cells. In tissue
culture, osmotically swollen astrocytes return toward normal volume over a period
of 15-30 min in a process termed regulatory volume decrease (RVD). RVD is due, in
part, to net efflux of taurine and other amino acids. Our objective in these
studies was to examine changes in astrocyte intracellular pH (pHi) which may be
related to taurine loss during RVD. We hypothesized net efflux of anionic taurine
abandons a proton inside the cell, thus lowering pHi. Primary cultures of
cerebral astrocytes were prepared from neonatal rats pups and grown on glass
coverslips. Confluent cells were loaded at 37 degrees C with the fluorescent pH
indicator BCECF. Fluorescence intensity ratios for excitation wavelengths of 440
nm and 494 nm (530 nm emission) were computed every 2 sec. Intensity ratios were
calibrated to pHi at the end of each experiment using 140 mM KCl plus 8.6 microM
nigericin at pH 7.4. pHi was measured in isoosmotic Hepes-buffered saline (290
mOsm) and then in hypoosmotic Hepes-buffered saline (200 mOsm) in the presence of
0.5 mM amiloride. Some solutions also contained 150 microM niflumic acid (NA).
Cellular taurine content was determined in parallel studies using HPLC. Changes
in pHi were compared between groups using Student's t-test with Bonferroni
correction. Significance was assumed if p < 0.05. In isoosmotic saline, mean +/-
SEM pHi was 7.58 +/- 0.04 and decreased to 7.35 +/- 0.09 after adding amiloride.
Hypoosmotic exposure caused a further drop in pHi of 0.29 +/- 0.03 within 15 min.
Recovery of pHi in isoosmotic saline was amiloride-sensitive. Subsequent
hypoosmotic exposure after recovery in isoosmotic saline produced a change in pHi
which was 81 +/- 9% of the change measured during the initial hypoosmotic
exposure. Taurine content decreased from 147 +/- 6 nmol/(mg protein) to 116 +/- 7
nmol(mg protein) during the 15 min hypoosmotic exposure in 0.5 mM amiloride. NA
significantly reduced the hypoosmotically induced change in pHi to 0.17 +/- 0.02
while completely blocking taurine loss. Assuming an intracellular buffering power
of 13 mM, the NA-sensitive intracellular acidification of cells during
hypoosmotic exposure in the presence of 0.5 mM amiloride corresponds to 1.6
mequiv/l additional intracellular H+. This increase in intracellular H+ content
is equivalent to approximately 32% of the NA-sensitive loss of taurine. The
association of changes in pHi with taurine efflux is supported by these data;
however, efflux of other weak acids may contribute to intracellular acidification
during astrocyte RVD and a significant portion of taurine must leave the cell
with a proton.
PMID- 9635038
TI - Effects of steroid hormones and cyclosporine A on taurine-transporter activity in
the RAW264.7 cell line.
AB - The activity of the taurine transporter is affected by various extracellular
stimuli, such as ions, hormones and stress. To assess the effects of steroid
hormones and cyclosporine A (CsA) on taurine-transporter activity, the murine
monocytic cell line, RAW264.7, was stimulated with dexamethasone (DM),
triamcinolone (TA), cortisone (CS), hydrocortisone (HCS), prednisone (PSN),
prednisolone (PSL) and methylprednisolone (MPSL) in the presence of 12-O
tetradecanoylphorbol 13-acetate (TPA). Treatment of the cell with TPA led to a
significant reduction in taurine-transporter activity. However, in the case of
the stimulation of the cells with steroid hormones in the presence of TPA, all of
the hormones reversed the TPA-induced reduction in the taurine-transporter
activity. Treatment of the cells with CsA led to a significant reduction in
taurine-transporter activity, but ionomycin (IM) alone did not affect taurine
transporter activity. However, IM reversed the TPA- and CsA-induced reduction in
taurine-transporter activity. These results showed that both IM and the
glucocorticoid hormones reversed TPA-induced reductions in taurine-transporter
activity but only IM reversed the CsA-induced reduction of transporter activity
in the RAW264.7 cell line.
PMID- 9635039
TI - The anion-exchanger AE1 is a diffusion pathway for taurine transport in rat
erythrocytes.
PMID- 9635040
TI - Molecular cloning and functional expression of an LLC-PK1 cell taurine
transporter that is adaptively regulated by taurine.
AB - Studies have shown that the renal tubular epithelium adapts to alterations in the
sulfur amino acid composition of the diet. The renal adaptive response has been
described in man, mouse, rat, dog, and pig. The observed phenomenon involves
increased or decreased initial rate activity of the NaCl-dependent taurine
transporter at the brush border membrane surface of the proximal tubule following
dietary manipulation of taurine. A cDNA encoding a taurine transporter has been
isolated from LLC-PK1 cells, designated pTAUT, and its functional properties have
been examined in Xenopus laevis oocytes. The nucleotide sequence of the clone
predicts a 621-amino acid protein with about 90% homology to other cloned taurine
transporter cDNAs. When expressed in oocytes the transporter displays a Km of 25
microM and is dependent on the presence of external sodium and chloride,
characteristics similar to taurine uptake by LLC-PK1 cells. The abundance of
pTAUT mRNA and protein were up-regulated in cells cultured in taurine-free medium
as compared with cells cultured in medium containing 500 microM taurine.
Activation of PKC by PMA had no effect on adaptive regulation of pTAUT mRNA and
protein, indicating that down-regulation of LLC-PK1 cell taurine transport
activity by PMA occurs at the post-translational level.
PMID- 9635041
TI - Regulation of the taurine content in Ehrlich ascites tumour cells.
PMID- 9635042
TI - Functional consequences of calcium uptake modulation by taurine in vivo and in
vitro.
PMID- 9635043
TI - Amplified effect of taurine on PCB-induced hypercholesterolemia in rats.
PMID- 9635044
TI - Taurine can ameliorate inflammatory bowel disease in rats.
AB - We previously reported that the protective effect of taurine against indomethacin
induced gastric mucosal injury was due to its antioxidant effects which inhibited
lipid peroxidation and neutrophil activation. In this study, we examined the
effect of taurine on reducing the inflammatory parameters of trinitrobenzene
sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. To induce
IBD, rats were given ethanolic TNBS intracolonically. The rats then received 500
mg/kg/day of taurine per orally. The rats were sacrificed one week after IBD
induction. Ulceration and inflammation of the distal colon with formation of
granuloma in the vehicle-treated IBD rats after two days of administration of
TNBS were observed. Treatment with 0.5 g/kg of taurine by the oral route
ameliorated colonic damage and decreased the incidence of diarrhea and adhesions.
Colon weight (an index of tissue edema) was markedly increased in the IBD rats
after administration of TNBS, but was significantly lower after taurine
treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was
substantially increased compared with that of the control. The taurine-treated
animals showed reduced MPO activity (35% lower) when compared with that of the
vehicle-treated animals. Taurine treatment decreased basal and formyl-methionyl
leucyl phenylalanine (FMLP) stimulated reactive oxygen generation in colonic
tissue of the IBD rat compared with vehicle treatment after one week. These
results suggest that administration of taurine reduced the inflammatory
parameters in this rat model of IBD by increasing the defenses against oxidative
insult.
PMID- 9635045
TI - The effects of taurine and biogenetically related sulfur-containing compounds on
the metabolism of and hypothermia by ethanol in the rat.
PMID- 9635046
TI - Modification by taurine of the metabolism and hypothermic effect of ethanol in
the rat.
PMID- 9635047
TI - Dietary taurine supplementation reduces plasma and liver cholesterol and
triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet.
AB - The effects of dietary taurine supplementation on plasma and hepatic lipid levels
and phospholipid profiles were evaluated in rats fed a high-cholesterol or a
cholesterol-free diet. Four groups of male rats were fed one of the following
diets for 5 weeks: cholesterol-free diet (CFD); high cholesterol diet (HCD); high
cholesterol, high taurine diet (HCHTD); or high taurine diet (HTD). Rats fed a
HCHTD had significantly lower plasma levels of total cholesterol (32% reduction),
LDL-cholesterol (37% reduction) and triglyceride (43% reduction) than rats fed a
HCD alone. Plasma concentrations of total cholesterol, LDL-cholesterol and
triglyceride were also significantly reduced in rats fed a HTD compared to rats
fed a CFD. Taurine supplementation to the HCD significantly reduced hepatic
cholesterol (50% decrease) and triglyceride (30% decrease) levels in rats.
Taurine supplementation to the CFD also significantly reduced the hepatic
triglyceride concentration (43% decrease) and elevated hepatic free fatty acid
levels (77% increase) compared to rats fed only a CFD. These results suggest that
dietary taurine supplementation is both hypocholesterolemic and
hypotriglyceridemic in rats whose body cholesterol status is high or normal.
PMID- 9635048
TI - Interrelationship between taurine and GABA.
PMID- 9635049
TI - Regulation of taurine biosynthesis and its physiological significance in the
brain.
AB - Cysteine sulfinic acid decarboxylase (CSAD), the rate-limiting enzyme in taurine
biosynthesis, was found to be activated under conditions that favor protein
phosphorylation and inactivated under conditions favoring protein
dephosphorylation. Direct incorporation of 32P into purified CSAD has been
demonstrated with [gamma 32P]ATP and PKC, but not PKA. In addition, the 32P
labeling of CSAD was inhibited by PKC inhibitors suggesting that PKC is
responsible for phosphorylation of CSAD in the brain. Okadaic acid had no effect
on CSAD activity at 10 microM suggesting that protein phosphatase-2C (PrP-2C)
might be involved in the dephosphorylation of CSAD. Furthermore, it was found
that either glutamate- or high K(+)-induced depolarization increased CSAD
activity as well as 32P-incorporation into CSAD in neuronal cultures, supporting
the notion that the CSAD activity is endogenously regulated by protein
phosphorylation in the brain. A model to link neuronal excitation,
phosphorylation of CSAD and increase in taurine biosynthesis is proposed.
PMID- 9635050
TI - Cell-damaging conditions release more taurine than excitatory amino acids from
the immature hippocampus.
PMID- 9635051
TI - Effects of NO-generating compounds on the uptake and release of taurine in the
mouse brain.
PMID- 9635052
TI - The in vivo release of taurine in the striatonigral pathway.
PMID- 9635053
TI - Taurine-induced potentiation is partially reversed by low-frequency synaptic
stimulation.
PMID- 9635054
TI - Treatment of rat brain membranes with taurine increases radioligand binding.
PMID- 9635055
TI - Taurine modulates glutamate- and growth factors-mediated signaling mechanisms.
PMID- 9635056
TI - Effect of taurine on human fetal neuron cells: proliferation and differentiation.
AB - The purpose of this study was to investigate the effect of taurine on human fetal
brain neuron cell proliferation and differentiation using a glial-free, pure
cerebral neuronal culture grown in a serum-free environment. We found that
taurine was necessary for neuronal survival and neurite extension. Taurine, on
the other hand, has a trophic effect on the human fetal brain cell, promoting
both proliferation and differentiation. Results showed that DNA synthesis of the
neurons was increased in a dose-dependent manner when neurons were cultured in
the medium containing taurine (100-6400 microM). The protein content of neuronal
cells was also significantly increased in the neurons treated with taurine as
compared to the control. At day 15, the expression of neuron-specific enolase
(NSE) was only detected in the neurons cultured in the medium containing taurine.
These results establish taurine as a putative human fetal brain neurontrophic
factor in the process of human brain development.
PMID- 9635057
TI - The role of taurine in osmotic, mechanical, and chemical protection of the
retinal rod outer segments.
AB - The ability of the photoreceptor cell to resist osmotic stress was examined by
incubating isolated frog retina in medium of varying osmolality. An electron
microscopic analysis of the rod outer segment following a severe hypoosmotic
insult revealed connections between adjacent disks and between disk rims and the
plasma membrane, which presumably provide mechanical stability to the rod outer
segment. One surprising result was the extent of the damage incurred by the
electrical signaling pathway of the photoreceptor cells subjected to a 50 mOsm
insult; only the distal P111 component of the ERG remained unaffected. Thus, the
rod outer segment is particularly resistant to osmotic-induced injury, presumably
because of the effective osmoregulatory actions of taurine. Incubation of retina
with tauret, retinylidentaurine, uncovered rose-like hexagonal structures on the
surface of the rod outer segment. These structures purportedly consist of
connections between disk rims and the plasma membrane of the rod outer segments.
Based on the influence of tauret, it is likely that the calcium dependence of
these channels is selective for retinoids. These data are discussed relative to
taurine's role in the process of rhodopsin regeneration and in the protection of
the rod outer segments against osmotic, mechanical and light induced damage.
PMID- 9635058
TI - Effects of taurine and light on retinal GABA content and the efflux of 14C-GABA
and 14C-aspartate from frog retina.
AB - GABA content of isolated, dark adapted frog retina was found to be 3.15 +/- 0.28
mM. After 30 minutes of exposure to intense light (200 lx), retinal GABA levels
increased about 70%. Interestingly, incubation of dark adapted retina for 30
minutes with medium containing 0.4 mM taurine also led to a 70% increase in GABA
levels. Since the light-induced elevation in GABA content was reduced over 50% by
a simultaneous injection of 0.02 mM strychinine, it is likely that the light
induced GABA change is partly mediated by the release of taurine from the retina
seen after light exposure. However, incubation of isolated retina with medium
containing increasing concentrations of taurine (1, 2 and 20 mM), caused a
progressive rise in 14C-GABA efflux from retina that was preloaded with 2.2
microM GABA and exposed to dim light (0.05 lx). It was also shown that taurine (1
and 5 mM) dramatically reduced 14C-aspartate efflux from retina preloaded with
radioactive aspartate and exposed to dim light conditions. By comparison, intense
light stimulation (40 lx) reduced basal 14C-aspartate efflux while dark exposure
increased 14C-aspartate loss from the isolated retina. We found that taurine
depressed the b-wave signal of frog retina, with the maximum effect occurring at
a concentration of 1 mM. Addition of strychnine (0.4 mM) reversed the taurine
effect on the b-wave, indicating that taurine receptors must be present in the
inner retina. By contrast, taurine (0.1-20 mM) had no effect on the P111
component of the ERG initiated by either aspartate or cobalt. However, taurine
exerted a modest depressant activity on P111 initiated by glutamate. The
significance of these data relative to the putative neurotransmitter function of
taurine in the inner retina is discussed.
PMID- 9635059
TI - Taurine-stimulated outgrowth from the retina is impaired by protein kinase C
activators and phosphatase inhibitors.
AB - Taurine increases neurite elongation of post-crush goldfish retinal explants, as
well as the number of outgrowing isolated cells from goldfish and rat retina in
culture. The trophic effect of taurine is related to an elevation in calcium flux
rather than increased cell proliferation. Since taurine regulates phosphorylation
in rat retina, we investigated if this process could be involved in the mechanism
of taurine action on outgrowth. Control and taurine-supplemented post-crush
goldfish retinal explants were cultured in the presence of protein kinase C
activators or phosphatase inhibitors, and the length of neurites was measured
after five days in culture. In some cases, there was an inhibition of the
stimulatory effect of taurine without a modification in basal outgrowth. In
others, outgrowth of control explants was also reduced. A certain level of
protein phosphorylation seems to be critical for the trophic effect of taurine in
the retina.
PMID- 9635060
TI - Unique pharmacological interactions of taurine and chelerythrine in the retina.
AB - The effects of taurine and chelerythrine (CHT) on ATP-dependent calcium uptake
and the phosphorylation of the approximately 20 kDa phosphoprotein in the retina
were compared. In the absence of the CHT, taurine stimulated ATP-dependent
calcium uptake and attenuated the phosphorylation of the approximately 20 kDa
phosphoprotein. On the other hand, CHT produced the opposite results in the
absence of taurine. When the two agents were used simultaneously, it was found
that CHT non-competitively inhibited the action of taurine to stimulate calcium
uptake, while taurine non-competitively inhibited the action of CHT to stimulate
the phosphorylation of the approximately 20 kDa phosphoprotein. The data present
an unusual pharmacological mechanism for controlling the signal transduction
pathway involving the two distinct cellular processes being studied. Given the
unique data, a control system is proposed in which the function of the
approximately 20 kDa phosphoprotein is linked to the stimulation of ATP-dependent
calcium uptake.
PMID- 9635061
TI - Increased phosphorylation of specific rat cardiac and retinal proteins in taurine
depleted animals: isolation and identification of the phosphoproteins.
AB - Partial depletion of the tissue levels of taurine in the alive animal stimulates
in vitro phosphorylation of both an approximately 20 kDa (94%) and an
approximately 44 kDa (85%) protein present in subcellular fractions of the rat
retina and heart. Tissue levels of taurine were reduced by feeding the animals
1.5% guanidinoethanesulfonic acid (GES) in their drinking water for 6 weeks. The
increase in the in vitro phosphorylation of both the approximately 20 kDa and
approximately 44 kDa proteins was reversed when the animals were subsequently
given 1.5% taurine in their drinking water for an additional 6 weeks. Isolation,
purification, tryptic digestion, and peptide sequence analysis of the retinal
approximately 20 kDa phosphoprotein suggest that it is histone H2B. However, the
results are ambiguous due to an impurity (< 25%) in the retinal preparation.
Sequence analysis of the approximately 44 kDa phosphoprotein indicates that it is
pyruvate dehydrogenase.
PMID- 9635062
TI - Extensive taurine depletion and retinal degeneration in cats treated with beta
alanine for 40 weeks.
PMID- 9635063
TI - The role of taurine in infant nutrition.
AB - The importance of taurine in the diet of pre-term and term infants has not always
been clearly understood and is a topic of interest to students of infant
nutrition. Recent evidence indicates that it should be considered one of the
"conditionally essential" amino acids in infant nutrition. Plasma values for
taurine will fall if infants are fed a taurine-free formula or do not have
taurine provided in the TPN solution. Urine taurine values also fall, which is
indicative of an attempt by the kidney to conserve taurine. The very-low-birth
weight infant, for a variety of reasons involving the maturation of tubular
transport function, cannot maximally conserve taurine by enhancing renal
reabsorption and, hence, is potentially at greater risk for taurine depletion
than larger pre-term or term infants, and certainly more than older children who
have taurine in their diet. Taurine has an important role in fat absorption in
pre-term and possibly term infants and in children with cystic fibrosis. Because
taurine-conjugated bile acids are better emulsifiers of fat than glycine
conjugated bile acids, the dietary (or TPN) intake has a direct influence on
absorption of lipids. Taurine supplementation of formulas or TPN solutions could
potentially serve to minimize the brain phospholipid fatty acid composition
differences between formula-fed and human milk-fed infants. Taurine appears to
have a role in infants, children, and even adults receiving most (> 75%) of their
calories from TPN solutions in the prevention of granulation of the retina and
electroencephalographic changes. Taurine has also been reported to improve
maturation of auditory-evoked responses in pre-term infants, although this point
is not fully established. Clearly, taurine is an important osmolyte in the brain
and the renal medulla. At these locations, it is a primary factor in the cell
volume regulatory process, in which brain or renal cells swell or shrink in
response to osmolar changes, but return to their previous volume according to the
uptake or release of taurine. While there is a dearth of clinical studies in man
concerning this volume regulatory response, studies in cats, rats, and dog kidney
cells indicate the protective role of taurine in hyperosmolar stress. The infant
depleted of taurine may not be able to respond to hyper- or hyponatremic stress
without massive changes in neuronal volume, which has obvious clinical
significance. The fact that the brain content of taurine is very high at birth
and falls with maturation may be a protective feature, or compensation for renal
immaturity Defining an amino acid as "conditionally essential" requires that
deficiency result in a clinical consequence or consequences which can be reversed
by supplementation. In pre-term and term infants, taurine insufficiency results
in impaired fat absorption, bile acid secretion, retinal function, and hepatic
function, all of which can be reversed by taurine supplementation. Therefore,
this small beta-amino acid, taurine, is indeed conditionally essential.
PMID- 9635064
TI - Quantitation of taurine and selenium levels in human milk and estimated intake of
taurine by breast-fed infants during the early periods of lactation.
AB - With these results we report the following: Taurine levels in human milk
decreased slightly during the early lactation period. The concentration of
taurine (406 +/- 174 nmol/ml) in colostrum was significantly higher than that
(335 +/- 115 nmol/ml) in mature milk. Selenium content of human milk also
decreased slightly during the early lactation period. The content of selenium
(28.6 +/- 19.6 ng/ml) in colostrum was significantly higher than that (1 5.1 +/-
5.9 ng/ml) in mature milk. A correlation was not found between the taurine and
selenium content of human milk. The intake of taurine and selenium by breast-fed
infants progressively increased with days postpartum. These results were due to
the significant increase in milk intake by infants. It is suggested that the
taurine and selenium levels in colostrum are more concentrated than those in
mature milk. However, the absolute intake of taurine and selenium by infants are
higher in mature milk.
PMID- 9635065
TI - Plasma concentration of taurine is higher in malnourished than control children:
differences between kwashiorkor and marasmus.
AB - Plasma free amino acids were determined in the plasma of severely malnourished
children under two years of age. A total of thirty-one patients and eleven
controls were evaluated: seventeen cases of kwashiorkor, eight cases of marasmus,
and six cases of marasmic-kwashiorkor. Fasting plasma samples were taken in the
morning on the day of admission. Fasting plasma samples were also taken from nine
patients at discharge after two months in the hospital where they received a
balanced diet as treatment. A partial reversal of the signs of malnutrition was
observed at discharge. In the whole group of patients ad admission, lower
concentrations of tyrosine, methionine, tryptophan, and leucine and higher
concentrations of aspartate, glutamate, and taurine were observed compared to
controls. Taurine continued to be elevated in the malnourished group at the time
of discharge. Marasmic children, as compared to controls, had high aspartate and
low tryptophan levels, but taurine levels were not significantly different from
controls. Kwashiorkor patients had low tyrosine, methionine, tryptophan, and
lysine, and significantly higher taurine plasma levels. The elevated
concentration of taurine might be the result of a redistribution of this amino
acid to provide specific tissues with the required amount for development.
PMID- 9635066
TI - The effect of dietary sulfur-containing amino acids on calcium excretion.
AB - The relationships between dietary protein and sulfur amino acid (methionine and
cystine or taurine) intakes and urinary calcium excretion were examined both in
animals and in young men. Thirty-two adult Wistar rats were divided into 4
groups, i.e., basal diet (group I), supplemented with albumin (II), methionine
and cystine (III), or taurine (IV). During the 5-week feeding period, food
consumption was recorded and 48 h urine samples were collected 4 times for each
rat. Urinary calcium, creatinine and sulfate were measured. The results showed
that the calcium and sulfate excretion in rats in group II and III were
significantly higher than rats in the basal diet group. In contrast,
supplementing a basal diet with taurine did not increase sulfate excretion and
failed to induce hypercalciuria. The same result was also observed in the study
carried out in Chinese young men. An increase in protein intake from 67 g to 107
g caused an increase in urinary calcium and sulfate. Supplementation with
methionine and cystine in an amount to simulate those in the high protein diet
had a similar effect. Adding taurine to the diet had no effect on urinary calcium
and sulfate excretion. About 60 percent of the supplemented taurine in the diet
was detected in the urine.
PMID- 9635067
TI - Taurine content in Chinese food and daily intake of Chinese men.
AB - The taurine content in Chinese food, including seafood, fresh water fish, meats
and some plants, was examined in this study. Seafood was freshly collected from 4
coastal areas in China. Meat and plant food samples were obtained from food
markets. The highest concentration of taurine was found in crustaceans and
molluses (300-800 mg per 100 g edible portion). The amount of taurine in fish was
variable. Beef, pork and lamb contained taurine in concentrations ranging from 30
160 mg per 100 g. No taurine was detected in hen eggs and plants. The daily
taurine intake of representative Chinese men (18-45 years old, 60 kg body weight,
light physical activity) was also studied in 1990 as a part of the Total Diet
Study. Representative food samples were collected from 12 provinces in 4 areas of
China. Samples were then combined and cooked according to food categories (meat,
seafood, vegetables, etc) The combined meat and seafood samples were analyzed for
taurine. The daily taurine intake of a standard man in the 4 areas was calculated
based on the amount of food intake obtained from the dietary survey and the
taurine concentration in the analyzed food samples. The result showed that the
daily taurine intake of a standard Chinese man in the 4 different test areas
ranged from 34 to 80 mg per day.
PMID- 9635068
TI - Effects of dietary taurine on auditory function in full-term infants.
AB - Three groups of neonates fed taurine supplemented infant formula, non
supplemented infant formula or breast milk, respectively, were studied from birth
to 12 weeks of age. In addition to the measurement of whole blood taurine
content, auditory function was monitored using auditory brainstem responses
(ABRs) and transient evoked otoacoustic emissions (TEOAEs). The results showed a
significant reduction in whole blood taurine concentration in the non
supplemented formula group. In addition, there was a significant drop in whole
blood taurine levels in all 3 groups over the first four weeks of life. ABR wave
latencies were significantly shorter in the non-supplemented group, with wave V
showing the greatest reductions. Falling taurine levels after full-term birth may
aid synaptic maturation/efficiency within the auditory system. TEOAE responses
were significantly larger over the low to mid frequencies in the breast fed group
suggesting improved middle ear function.
PMID- 9635069
TI - Relationship of childhood abuse and household dysfunction to many of the leading
causes of death in adults. The Adverse Childhood Experiences (ACE) Study.
AB - BACKGROUND: The relationship of health risk behavior and disease in adulthood to
the breadth of exposure to childhood emotional, physical, or sexual abuse, and
household dysfunction during childhood has not previously been described.
METHODS: A questionnaire about adverse childhood experiences was mailed to 13,494
adults who had completed a standardized medical evaluation at a large HMO; 9,508
(70.5%) responded. Seven categories of adverse childhood experiences were
studied: psychological, physical, or sexual abuse; violence against mother; or
living with household members who were substance abusers, mentally ill or
suicidal, or ever imprisoned. The number of categories of these adverse childhood
experiences was then compared to measures of adult risk behavior, health status,
and disease. Logistic regression was used to adjust for effects of demographic
factors on the association between the cumulative number of categories of
childhood exposures (range: 0-7) and risk factors for the leading causes of death
in adult life. RESULTS: More than half of respondents reported at least one, and
one-fourth reported > or = 2 categories of childhood exposures. We found a graded
relationship between the number of categories of childhood exposure and each of
the adult health risk behaviors and diseases that were studied (P < .001).
Persons who had experienced four or more categories of childhood exposure,
compared to those who had experienced none, had 4- to 12-fold increased health
risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold
increase in smoking, poor self-rated health, > or = 50 sexual intercourse
partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in
physical inactivity and severe obesity. The number of categories of adverse
childhood exposures showed a graded relationship to the presence of adult
diseases including ischemic heart disease, cancer, chronic lung disease, skeletal
fractures, and liver disease. The seven categories of adverse childhood
experiences were strongly interrelated and persons with multiple categories of
childhood exposure were likely to have multiple health risk factors later in
life. CONCLUSIONS: We found a strong graded relationship between the breadth of
exposure to abuse or household dysfunction during childhood and multiple risk
factors for several of the leading causes of death in adults.
PMID- 9635070
TI - Youth violence in the United States. Major trends, risk factors, and prevention
approaches.
AB - Violence among youths is an important public health problem. Between 1985 and
1991, homicide rates among youths 15-19 years of age increased 154% and remain,
today, at historically high levels. This paper reviews the major trends in
homicide victimization and perpetration among youths over the last decade, the
key risk factors associated with violence, and summarizes the many primary
prevention efforts under way to reduce violence. Previous research points to a
number of factors that increase the probability of violence during adolescence
and young adulthood. Some of these factors include the early onset of aggressive
behavior in childhood, social problem-solving skill deficits, exposure to
violence, poor parenting practices and family functioning, negative peer
influences, access to firearms, and neighborhoods characterized by high rates of
poverty, transiency, family disruption, and social isolation. Efforts to address
some of the primary risk factors for violence are under way across the United
States, but evaluations to confirm program effectiveness are needed.
PMID- 9635071
TI - Family violence curricula in U.S. medical schools.
AB - INTRODUCTION: Family violence (adult domestic violence, child abuse/neglect, and
elder abuse) is endemic. Victims of family violence are seen in every venue of
health care, yet physicians do not routinely inquire about abuse, even when
patients present with obvious clinical characteristics. Although a comprehensive
health care response is key to a coordinated community-wide approach to family
violence, most practicing physicians have never received education in any aspect
of family violence, including child abuse. This paper reports the results of a
survey of family violence instruction in medical schools. METHODS: A written
survey of medical school deans and student representatives of all 126 U.S.
medical schools was conducted to (1) determine curriculum content in family
violence, (2) assess differences between deans' and students' perceptions of
curricular offerings, and (3) compare the results of the current survey with
those of an earlier curriculum survey conducted in 1987. RESULTS: The majority of
deans reported existing curriculum in all three topic areas of family violence.
Compared to the 1987 survey, more deans reported existing curriculum in family
violence. However, neither total instructional time nor curriculum during
clinical training increased. Moreover, student and dean responses were discrepant
regarding awareness of curriculum in domestic violence and elder abuse.
CONCLUSION: Despite an increase in the number of schools reporting curriculum in
family violence, there does not appear to be increased attention to this problem,
at least as measured by time devoted to teaching. Insights from this descriptive
survey can promote ongoing efforts toward comprehensive curriculum development in
family violence.
PMID- 9635072
TI - Recommended components of health care provider training programs on intimate
partner violence.
AB - Programs that are effective in training health care providers to recognize and
meet the needs of victims of intimate partner violence must be identified and
replicated. The Centers for Disease Control and Prevention (CDC) has developed
criteria for use in developing, enhancing, and evaluating such programs. CDC
developed these criteria as a result of continuing efforts to provide useful
products for constituents through literature reviews and consultations with
experts in the field; evaluations of training programs; creation of an inventory
and annotated bibliography of health care provider training programs in the
United States and Canada; and development of a framework to assist hospitals and
health centers in evaluating their training programs. Training should begin while
providers are in professional school and continue in the health care setting.
Curricula should be multidisciplinary and should provide information, promote
clinical skills, and effectively link providers with resources. Evaluation should
assist programs in determining providers' needs and identifying appropriate
materials, trainers, and training strategies. CDC is working to establish
scientific evidence that provider training programs are effective and to share
successful models with others. Providers have an important role in stopping and
ultimately preventing intimate partner violence, but they are not alone in this
effort. They need to know how to access the growing network of assistance
including women's advocates, the criminal justice system, and other members of
increasingly dynamic community coalitions.
PMID- 9635073
TI - Assessing family violence interventions.
PMID- 9635074
TI - Commentary on the federal role in clinical prevention research.
AB - Effective clinical prevention practice is the objective of the long journey from
laboratory and epidemiologic studies to clinical understanding, interventions,
and prevention practice with individual patients. The ability to ask ever more
fundamental questions about the molecular basis of disease, as is rapidly being
developed by NIH's Human Genome Project, promises to make this journey even
longer and more complicated, but eventually to make screening and intervention
for preventable disease even more amenable to clinical intervention. As we expect
in the future, much of what we currently do in clinical prevention practice had
its genesis in earlier federal support for basic and clinical research. We
comment on the content and major points of the papers on the federal role in
prevention research. These papers, in addition to describing the past
accomplishment, current state, and future opportunities for prevention research,
raise questions about the ultimate application of the enormous and successful
national investment in prevention research. A fault line exists among the
increasing knowledge of prevention practice, the rapid changes in the way
services are delivered, and demonstration of the effectiveness of prevention
procedures applied for the good of the whole population. The federal agencies
most concerned with the application of prevention knowledge are those most
limited in their research budgets: the Agency for Health Care Policy and Research
(AHCPR) and the Centers for Disease Control and Prevention (CDC). The National
Institutes of Health (NIH), with the greatest research dollars for investment,
also has the broadest mandate for investment in research. Meeting all the demands
to fund high-quality research is challenging; however, NIH may have review
procedures that disadvantage clinical researchers and, among these, applied
prevention researchers. The restructuring of the health care system by managed
care promises opportunity for more effectiveness research. However, the same
competition that fosters the development of managed care may limit the extent of
prevention experimentation and the dissemination of results. Current national
concerns for the weakening of support for clinical research are in part due to
the reduced availability of patient care revenue to support clinical research
brought about by managed care. The academic and practice communities that share
concern for prevention research should recognize the increasing gap between basic
and applied prevention knowledge. Those committed to the clinical application of
this knowledge should encourage increased federal research support to assure that
what we think we know is indeed so, that what is efficacious is available to all
in the society that so generously supports research.
PMID- 9635075
TI - Clinical preventive services research.
PMID- 9635076
TI - Prevention research at the National Institutes of Health.
AB - Prevention of disease and disability and preservation of health are compelling
strategies that are endorsed by the public, health care providers, and
researchers. Despite this general acceptance of the concept, the "devil is in the
details." What can and should be recommended with confidence to the public and
health care providers regarding prevention and how can these recommendations be
implemented? Prevention programs should be based on durable evidence of efficacy
and should assure that the benefits of interventions and changes exceed the
risks. The latter is particularly important for population-based primary
prevention because many are influenced but fewer may benefit. Prevention research
must provide the evidence of benefit and risk. The responsibility of the National
Institutes of Health (NIH) is to develop the scientific basis for prevention and
to train prevention scientists who are responsible for creating this science
base. The interpretation and dissemination of information from research studies
are important and necessary aspects to assure translation of the science into
personal and public health practices. The components of prevention research are
investigation of the factors that place individuals and groups at risk of disease
and disability; trials of the interventions that can modify this risk; and
testing the approaches that can effectively implement beneficial changes. NIH is
committed to addressing these endeavors, and its individual Institutes and
Centers support a broad portfolio of prevention research. This paper will provide
an overview of NIH support, the functional relationships of prevention research
within NIH, and background information that can be useful to those interested in
research.
PMID- 9635077
TI - Fifty years of applied population-based prevention research at the Centers for
Disease Control and Prevention.
PMID- 9635078
TI - Cardiovascular disease prevention research at the National Heart, Lung, and Blood
Institute.
PMID- 9635079
TI - Health services research agenda for clinical preventive services.
PMID- 9635080
TI - Broadening the evidence base for evidence-based guidelines. A research agenda
based on the work of the U.S. Preventive Services Task Force.
AB - Evidence-based evaluations of clinical preventive services help define priorities
for research in prevention as part of primary health care. In this article, we
draw on our experiences with the U.S. Preventive Services Task Force (USPSTF) to
outline some major areas where research is needed to define the appropriate use
of specific screening tests, counseling interventions, immunizations, and
chemoprophylaxis. Areas of particular importance included research to: (1)
Identify effective and practical primary care interventions for modifying
personal health practices of patients, especially around issues such as diet,
exercise, alcohol and drug use, and risky sexual behavior; (2) Clarify the
optimal periodicity for certain screening tests and counseling interventions; (3)
Identify practical ways to allow patients to share decision-making about
preventive care, especially for services of possible but uncertain benefit; (4)
Examine the most sensitive and efficient ways to identify high-risk groups who
may need different services than the average population; and (5) Expand the use
of decision-analysis and cost-effectiveness analysis to help identify optimal use
of clinical preventive services. Given the difficulty of large, prospective
trials, we discuss the use of alternative research designs to fill in critical
gaps in the evidence for the effectiveness of specific services. Finally, we note
several issues of increasing importance that may need to be addressed by future
work of the USPSTF: what are the most reliable and effective ways to (1) measure
and (2) improve the delivery and quality of preventive care provided in the
primary care setting.
PMID- 9635081
TI - Prevention and primary care research for children. The need for evidence to
precede "evidence-based".
AB - Medical care in the United States continues to face tremendous financial
pressures. Public and private health policy claim to encourage primary care and
preventive services, but also discourage services that have not been demonstrated
to be effective and/or cost-effective. This article suggests a model to
illustrate the conceptual relationship between traditional American medical care
and "evidenced-based" medicine. It further examines how the lack of an adequate
research base makes a move to purely evidence-based care premature for primary
care and prevention services. The paper defines a new conceptual statistic, the
uncertainty index, as the proportion of non-refuted current practice that is also
not corroborated by research evidence. The greater the uncertainty index, the
less appropriate is a clinical model restricted to evidence-based care. Specific
theoretical barriers to outcomes research in prevention are discussed and simple
criteria to determine the desirable components of care are suggested. The need
for theoretical and empirical research into primary care and prevention,
especially for children, is emphasized. Care that is of low risk, not of
extremely high cost, and that is generally believed useful by the community of
practitioners is particularly desirable in the absence of data refuting its
value.
PMID- 9635082
TI - Prevention research. A call to action.
PMID- 9635083
TI - Adverse childhood experiences. A public health perspective.
PMID- 9635084
TI - What explains the negative consequences of adverse childhood experiences on adult
health? Insights from cognitive and neuroscience research.
PMID- 9635085
TI - Adverse childhood experiences and trauma.
PMID- 9635086
TI - In response to the September-October article entitled "Violence and adverse
pregnancy outcomes: a review of the literature and directions for future
research".
PMID- 9635087
TI - DoEpi. Computer-assisted instruction in epidemiology and computing and a
framework for creating new exercises.
AB - DoEpi is a series of computer exercises and a framework for making new exercises
based on the Epi Info programs for epidemiologic computing. The system contains
three outbreak investigations, a research survey, four exercises in advanced Epi
Info programming, and four exercises in public health surveillance. The exercises
are available via the Internet (www.cdc.gov, under "Publications, Products, and
Software") with provision for CME and CEU credit from the Centers for Disease
Control and Prevention. They can serve as a useful adjunct to lectures and
textbooks in teaching epidemiology or epidemiologic computing. A new DoEpi
exercise with hypertext, low-resolution photographs, questions, answers, and an
examination can be constructed in hours rather than weeks or months using an
Exercise Development "wizard" provided as part of the instructor's module. Epi
Info exercises with data files and customized programs require more work to
construct but can be added by those with the necessary skills. DoEpi exercises
can be used in a variety of ways for different curricula and students of
different background levels, including those with English as a second language.
Translation of DoEpi exercises into other languages is facilitated by the
instructor's module, and construction of new exercises with locally suitable
materials is encouraged. DoEpi is based on DOS programs to allow the widest use.
The format lends itself to conversion to hypertext programs in the Microsoft
Windows and Internet formats at a future date.
PMID- 9635089
TI - The U.S. Preventive Services Task Force Guide to Clinical Preventive Services,
Second Edition. AMA Council on Scientific Affairs.
AB - A resolution, introduced by the American College of Preventive Medicine at the
1996 American Medical Association (AMA) Annual Meeting, asked the AMA to
recommend to physicians the use of the United States Preventive Services Task
Force's Guide to Clinical Preventive Services, Second Edition. In response to
that resolution, the AMA's Council on Scientific Affairs has reviewed and
evaluated this publication. The recommendations of the Council on Scientific
Affairs on the use of the Guide to Clinical Preventive Services, Second Edition,
by clinicians and medical educators are included in this report. These
recommendations were adopted as AMA Policy at the AMA Annual Meeting in June
1997.
PMID- 9635090
TI - Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men.
AB - Genetic factors that could mediate the pathogenesis of male reproductive
disorders are largely unclear. Polymorphisms of cytochrome P4501A1 (CYP1A1), a
key enzyme in the extrahepatic metabolism of lipophilic xenobiotics, have been
shown to influence susceptibility to xenobiotics. Here, CYP1A1 polymorphisms were
investigated in 134 infertile Caucasian men. The frequencies of the Mspl
polymorphism in the 3'-flanking region of the CYP1A1 gene and a mutation in exon
7 causing an isoleucine-valine exchange (IVE) in the heme-binding region of the
enzyme were increased among infertile men when compared with those of unselected,
healthy male controls (odds ratio (OR)) 1.4, Cl95 0.68-2.89 for Mspl
polymorphism; OR 2.4, Cl95 0.83-6.95 for IVE). Patients with normozoospermia
revealed the highest frequencies for both polymorphisms (n = 8; OR 4.5, Cl95 0.97
20.91 for Mspl polymorphism; OR 13.7, Cl95 2.53-74.13 for IVE). ORs for the IVE
exceeded the values calculated for the Mspl polymorphism. These preliminary
results suggest that genetic variation in the metabolism of xenobiotics may
codetermine individual susceptibility to infertility.
PMID- 9635091
TI - Effect of chronic administration of Tamoxifen on fertility in male bonnet monkeys
(Macaca radiata).
AB - Administration of Tamoxifen via the Alzet pump at a rate of 50 micrograms hr-1
for 90 days in the adult male bonnet monkeys Macaca radiata had no effect on the
serum testosterone concentration determined at 10 AM and 10 PM as well as total
sperm count determined at 15-day intervals over a period of 260 days. However, a
significant reduction in sperm motility was observed beyond 90 days up until the
225th day. Breeding studies conducted from day 90 to 260 revealed that these
males were infertile.
PMID- 9635092
TI - A comparative study of the EpiScreen kit and a conventional method for the
determination of seminal alpha-glucosidase activity.
AB - Low alpha-glucosidase activity in seminal plasma is a marker of epididymal
obstruction. The criterion standard for determining activity is the epididymal
specific method, whereby the neutral iso-enzyme, specifically produced by the
epididymis, is measured. A kit that determines total alpha-glucosidase activity
(neutral iso-enzyme and the acid iso-enzyme originating from the prostate) has
become available. The objective of the laboratory-based study was to compare
alpha-glucosidase activity values measured by both the EpiScreen and the
epididymal specific method, to determine if the kit may provide reliable results
to substitute the neutral iso-enzyme specific method in the routine clinical
setting. The neutral iso-enzyme activity according to both methods was measured
in seminal plasma of 23 post-vasectomy and 24 normozoospermic patients.
Significant differences (P < 0.05) were found between the activities measured
according to both methods, but these differences pertained mostly to high values
(> 40 mU ejaculate-1), which was not clinically significant. In conclusion, the
epididymal specific method is best suited for research purposes, but the
EpiScreen kit is convenient for routine use in infertility clinics.
PMID- 9635093
TI - Measurement of calcium influx in surface-fixed single sperm cells: efficiency of
different immobilization methods.
AB - Calcium fluxes across the plasma membrane of spermatozoa are part of the signal
transduction pathway during sperm capacitation. To identify the topography, the
time sequence and frequency of calcium fluxes in motile human spermatozoa,
individual spermatozoa have to be locally immobilized in a measurement chamber to
allow the quantification of ionized calcium by use of a microspectro-photometric
method (FURA-2AM). In this study, we compared different immobilization methods
using agarose-, gelatin-, laminin- and poly-L-lysine-coated glass slides. Optimal
results were obtained with poly-L-lysine coating, which permitted the adhesion of
motile spermatozoa that could be analysed microspectro-photometrically. The loss
of adherent spermatozoa during the washing procedures was below 10%. However, a
major disadvantage of poly-L-lysine coating is that this polymer itself induces a
low calcium flux in spermatozoa. Comparing all tested variations, laminin offered
the best adhesion result without any detectable effects on calcium fluxes. Our
method allowed the rapid change of incubation fluid and calcium concentrations
around individual motile spermatozoa and the reproducible quantification of
calcium fluxes in single motile spermatozoa.
PMID- 9635094
TI - Heterogeneity in the presence of CD4-like molecules on human spermatozoa.
AB - The object of the present study was to study if there are differences in the
presence of CD4-like molecules on human ejaculated spermatozoa in fertile donors
and infertile patients (with globozoospermia). Indirect and absorption enzyme
linked immunosorbent assay and indirect immunofluorescence were applied. The
enzyme-linked immunosorbent assay data showed that monoclonal anti-human CD4
antibody recognizes an epitope common to the human spermatozoa with normal
morphology and round-headed spermatozoa. Localization of the antigenic
determinants, identified by anti-human CD4-monoclonal antibody, in the acrosomal
region, including equatorial segment, postnuclear cap and tail was determined in
normozoospermic samples. A positive reaction was found on the sperm head both in
the acrosomal and postacrosomal region of some round-headed spermatozoa in the
samples with globozoospermia. The tails of the normozoospermic spermatozoa and of
some round-headed spermatozoa were weakly immunopositive. The results of the
experiments carried out are evidence of heterogeneity in the presence of CD4-like
antigen determinants on human spermatozoa. These data increased the information
about the CD4-antigen characteristic of the spermatozoa from fertile donors and
infertile patients.
PMID- 9635095
TI - Wave parameters of the sperm flagellum as predictors of human spermatozoa
motility.
AB - We characterized the undulatory movement of the sperm's flagellum as a sigmoid
wave by measuring the absolute and linear speed of the sperm, period, amplitude
and length of the flagellum's wave, and the segment comprised between the head
and the origin of the movement in the flagellum. These parameters were correlated
with traditional ones used to determine the pattern of movement of the sperm. Our
results show that wave parameters are useful predictors of sperm motility. They
correlate among themselves, and thus, a few wave parameters may characterize the
sperm motility. The advantage of wave parameters is that they can be easily
obtained and can be eventually associated to the sperms' internal morphology.
PMID- 9635096
TI - Induction of acrosome reaction by low temperature is comparable to physiological
induction by human follicular fluid.
AB - The acrosome reaction was induced by means of low temperature or human follicular
fluid (FF) in spermatozoa from 18 patients. Live acrosome-reacted spermatozoa
were determined with the triple-stain technique. Both inducers of acrosome
reaction had a highly significant correlation with the percentage of acrosome
reacted spermatozoa after induction of the acrosome reaction: (r = 0.9190; P <
0.0001) and the inducibility of AR (r = 0.8472; P < 0.0001). This might indicate
that both the non-physiological (low temperature) and the physiological (FF)
inducers use the same signal transduction pathway, and demonstrates the
usefulness of low temperature induction for diagnostic purposes.
PMID- 9635097
TI - Effect of bradykinin on kinematic parameters of human spermatozoa.
PMID- 9635098
TI - Carbohydrate deficient transferrin measurement.
PMID- 9635099
TI - Rational use of clinical chemistry investigations: from diagnoses to processes.
PMID- 9635100
TI - Standardization of steroid hormone assays.
PMID- 9635101
TI - CA 19-9 as a marker for gastrointestinal cancers: a review.
PMID- 9635102
TI - Traceability and uncertainty in analytical measurements.
PMID- 9635103
TI - Cardiac troponins in patients with renal dysfunction.
AB - Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were measured in 198
patients with renal dysfunction [132 men: median (range) age 66.1 (8.2-90.3)
years]. cTnT was measured by two methods: ELISA and Enzymun (Boehringer Mannheim
UK, Lewes, UK), both with a detection limit of 0.05 microgram/L in 179 and 78
patients, respectively. cTnI was measured in 80 patients by the OPUS plus and
OPUS Magnum systems (Dade-Behring, Milton Keynes, UK) with a detection limit of
0.5 microgram/L. Patients were classified as having chronic renal impairment
(CRI), chronic renal failure (CRF), acute renal failure including those with
multiple organ failure on renal replacement therapy (ARF), and patients with
chronic renal failure treated with haemodialysis (HD). Cardiac troponins were
detectable in the serum of patients with renal dysfunction. cTnT was detectable
in 113/179 (63.1%) and 33/78 (42.3%) by the ELISA and Enzymun methods
respectively. cTnI was detectable in 17/80 (21.3%). cTnT (ELISA and Enzymun
methods) and cTnI were detectable with increased frequency in the CRF, HD and ARF
patient groups compared with the CRI group. Cardiac troponin concentrations did
not correlate with serum creatine kinase (CK) activity, CK-MB, or urea or
creatinine levels. Serial cardiac troponin measurements may be required to
confirm or exclude a diagnosis of acute coronary syndromes in patients with renal
dysfunction.
PMID- 9635104
TI - Clinical and biochemical determinants of plasma lipid peroxide levels in type 2
diabetes.
AB - The enhanced risk and increased severity of atheroma in diabetes is well
recognized but, as yet, incompletely explained. A cross-sectional study of
vascular disease risk factors in a group of type 2 diabetic patients from South
West Scotland has revealed an association between glycaemic control, assessed by
HbAl level and plasma lipid peroxides measured by a specific high-performance
liquid chromatography method. Duration of diabetes appeared to be a subsidiary
contributor to lipid peroxidation. We suggest this evidence supports the
importance of glycaemic control in modulating glyco-oxidative mechanisms probably
crucial to production of diabetic complications. Atherosclerosis prevention in
diabetes may hinge on exemplary simultaneous control of both hyperglycaemia and
hyperlipidaemia.
PMID- 9635105
TI - Biochemical markers of acute myocardial infarction: strategies for improving
their clinical usefulness.
AB - We investigated the early diagnostic utility, including incremental value, of the
serum cardiac markers creatine kinase (CK), CK-MB (mass and activity
measurements), cardiac troponin T, and myoglobin in the diagnosis of acute
myocardial infarction (AMI) in patients presenting to a major teaching hospital
with chest pain and non-diagnostic electrocardiographs (ECG). The reference
diagnosis of acute myocardial infarction was made by a single, independent
cardiologist using World Health Organization criteria. CK and CK-MB mass were the
only significant predictors of AMI at presentation to the Emergency Department.
Logistic regression analysis revealed that CK did not significantly predict (P =
0.23) myocardial infarction once CK-MB mass was in the model. Using test results
on follow up, in addition to presentation CK-MB mass, change in CK-MB mass was
the only other significant independent predictor of AMI. Likelihood ratios for
various levels of the significant markers in the logistic regression are given.
In conclusion, CK-MB mass measurement was the only useful serum cardiac marker
for the diagnosis of AMI in patients presenting with chest pain with non
diagnostic ECGs.
PMID- 9635106
TI - Tetranectin levels in patients with acute myocardial infarction and their
alterations during thrombolytic treatment.
AB - Tetranectin (TN), a new regulator of fibrinolysis, was studied in the plasma of
60 patients with acute myocardial infarction (AMI) and 30 healthy subjects (HS),
in relation to D-dimer (DD) and alpha 2-plasmin inhibitor (alpha 2-PI), to
investigate its possible involvement in the pathophysiology of AMI. Thirty
patients underwent thrombolytic treatment with fibrin-specific plasminogen
activator (rt-PA) (group A); the other 30 patients, according to the exclusion
criteria, were conventionally treated (group B). Twenty of the thrombolysized
patients established early recanalization (subgroup A1), while 10 failed to
respond to thrombolytic treatment (subgroup A2). Median (interquartile range),
baseline plasma TN levels were lower in AMI patients compared to HS [8.27 (2.75)
mg/L versus 12.1 (0.55) mg/L, P < 10(-6)]. In subgroup A1, TN increased at the
end of rt-PA infusion and returned to the baseline levels 12 h later. A positive
association between DD and TN release (3 h level minus baseline level) was found
(rs = 0.48, P = 0.03) in subgroup A1. No significant alterations of TN levels
were observed during therapy in subgroup A2 and group B. TN, DD and alpha 2-PI
concentrations in group B remained relatively constant during the study period.
This study provides evidence of a significant decrease of TN levels in AMI
patients compared to healthy subjects and of a remarkable difference in the
evolution of TN levels during thrombolytic treatment with rt-PA between
recanalized and non-recanalized AMI patients. Thus, an involvement of TN in the
formation and dissolution of fibrin clot in AMI patients is worthy of further
investigation.
PMID- 9635107
TI - Apo A-I and apo E concentrations in cerebrospinal fluids of patients with acute
meningitis.
AB - It has been demonstrated that apolipoproteins found in cerebrospinal fluid (CSF)
play an important role in lipid metabolism in the central nervous system (CNS).
Previously we reported that CSF apo A-I levels increased with the severity of
neurological damage in poliovirus-infected macaques. In the present study, apo A
I was quantitatively analysed in CSF from patients with or without neurological
diseases. In controls, CSF apo A-I level was significantly higher in males; 3.83
(0.40) mg/L, mean (SEM) (n = 19) compared with females, 2.42 (0.26) mg/L (n = 23,
P < 0.05). CSF apo A-I concentrations in patients with acute meningitis increased
at the active stage, 7.74 (1.78) mg/L (n = 10), but returned to basal
concentrations at the convalescent stage 2.72 (0.38) mg/L (n = 10), while the CSF
apo A-I level in patients with other neurological diseases remained in the same
range as in controls. By contrast, CSF apo E was consistently elevated at either
stage of acute meningitis. Furthermore, it was found that the levels of CSF apo A
I, but not of apo E, correlated positively with CSF albumin concentrations. These
findings suggest that the CSF apo A-I and apo E have different origins and may
play different roles in the lipoprotein metabolism in CNS.
PMID- 9635108
TI - Globin chains analysis: improved resolution by electrophoresis in urea-acetic
acid-Triton X-100.
AB - To improve the resolution and rapidity of globin chains separation, we have
modified the basic technique of globin chain electrophoresis in urea-acetic acid
Triton X-100. Haemolysates from anticoagulated cord or adult blood samples were
submitted to urea-acetic acid-Triton X-100 polyacrylamide gel electrophoresis
using a 15% polyacrylamide gel cast in a mini slab cell which allows a rapid
analysis of globin chains samples. After staining proteins with Coomassie
brilliant blue R-250, the relative amounts of globin chains were determined by
scanning. This new procedure has allowed us to obtain a better separation of the
normal and abnormal globin chains than described previously. All the normal
globin chains, i.e. A gamma, G gamma, delta, beta and alpha, are well separated
by this modified technique. Semi-quantification of the G gamma/A gamma ratio has
been performed. This simple and rapid method is also suitable for the global
identification of the globin chain involved in the most common abnormal
haemoglobin variants, except beta-S.
PMID- 9635109
TI - Comparison of the Bio-Rad Porphyrin Column Test with a simple spectrophotometric
test for total urine porphyrin concentration.
AB - We compared two screening methods for increased urine porphyrin concentration and
compared the results with a high-performance liquid chromatography (HPLC) method.
The screening methods were the Bio-Rad (Porphyrin) Column Test and a simple
spectrophotometric method. Results were obtained for urines with three different
porphyrin patterns. Both screening methods were easy to perform. The accuracy and
precision of the spectrophotometric method were both slightly better than that of
the Bio-Rad Column Test. Recovery measurements in samples with different
porphyrin patterns varied between 73% and 59% (n = 12) for the spectrophotometric
method and between 82% and 116% (n = 12) for the Bio-Rad Column Test as compared
to HPLC. Between batch precision measurements revealed coefficients of variation
for spectrophotometric and Bio-Rad methods for 2%-4% and 4%-10%, respectively.
The recovery of the porphyrins illustrates the Bio-Rad Column Test to be more
susceptible to variation in urine porphyria composition. Both methods will show
satisfactory results in cases of overt porphyria because of the high urine
porphyrin concentration.
PMID- 9635110
TI - The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and
its significance in the mechanism of lead toxicity on haem synthesis.
AB - Protoporphyrin and zinc-protoporphyrin were measured in the erythrocytes of
normal subjects, workers exposed to lead and patients with iron deficiency and
erythropoietic protoporphyria (EPP). Results showed significantly higher levels
of zinc-protoporphyrin in the lead-exposed workers (P < 0.0001), patients with
iron deficiency (P < 0.0001) and EPP patients (P < 0.001) compared with normal
subjects. The lead-exposed workers showed the highest levels of zinc
protoporphyrin, which were significantly greater than both the iron-deficient and
EPP patients (P < 0.0001). They also showed a higher ratio of zinc-protoporphyrin
to free protoporphyrin compared with normal subjects (P < 0.0001) but no
significant difference in this ratio was found when compared with iron-deficient
patients (P = 0.1). These results are discussed in light of the controversy
concerning the mechanism of formation of zinc-protoporphyrin in lead exposure.
PMID- 9635111
TI - Dietary treatment of hypercholesterolaemia: lack of relationship between
individual response and genetic variation at the lipase loci. The Fluvastatin
Genotyping Group.
AB - The individual benefits of dietary therapy for hyperlipidaemia are known to be
unpredictable. Variants at the lipoprotein lipase gene have been shown to
associate with atherogenic lipoprotein phenotypes and the delayed clearance of
triglyceride-rich lipoproteins. Together with variants of the closely homologous
hepatic lipase gene, these may influence the extent of amelioration of plasma
lipoprotein concentrations seen in dyslipidaemic patients treated with a low
saturates/low cholesterol diet. We correlated the lipid changes seen following an
8-week diet in 83 subjects with primary hypercholesterolaemia (fasting plasma
cholesterol > 6.5 mmol/L) with alleles of three restriction polymorphisms (LPL
Hind III and Pvu II; HL-Msp I). Although dietary changes produced a significant
improvement in fasting lipids [total cholesterol falling by 5.2% (range -27.9% to
+24.3%) and low-density lipoprotein cholesterol reduced by 6.0% (-30.5% to
+29.3%)], no significant difference in response between different genotypes could
be detected.
PMID- 9635112
TI - Increased gamma-glutamyltransferase in hypertriglyceridaemia: the value of
carbohydrate-deficient transferrin measurement.
PMID- 9635113
TI - Albumin concentration is underestimated in frozen urine.
PMID- 9635114
TI - Audit of the clinical utility of antibodies to endomysium and gliadin as markers
of coeliac disease.
PMID- 9635115
TI - A simple method for the detection of lactate dehydrogenase isoenzymes M:H ratio
by gel filtration.
PMID- 9635117
TI - What is the best formula for predicting osmolar gap?
PMID- 9635116
TI - A case of factitious hypocalcaemia.
PMID- 9635118
TI - Preclinical biology of recombinant human hemoglobin, rHb1.1.
AB - Historically, the development of hemoglobin based oxygen carriers, HBOCs, were
confounded by issues related to activation of the complement cascade and other
inflammatory processes, renal toxicity, and significant systemic
vasoconstriction. However, with shortages in the blood supply, the risk of
infectious agent contamination, and delays associated with complete crossmatch as
well as transfusion reactions, HBOC development has assumed greater importance. A
successful HBOC in addition to having favorable oxygen binding parameters and
colloid oncotic properties, must also have a low toxicity profile, be
nonimmunogenic, have positive rheologic properties, and have an adequate in vivo
half life. In addition, it must also be stable in vivo and not undergo
significant oxidation to methemoglobin or release heme or iron in the
vasculature. The preclinical studies which have been designed and executed to
address these requirements for recombinant human hemoglobin rHb1.1 serve as the
focus of this review. Recombinant Hb1.1 represents the first HBOC to enter
clinical trials as a recombinant product in distinction to other HBOCs which are
derived from bovine or outdated human blood. While currently in phase II clinical
trials, the preclinical biology which has increased our understanding of this
molecule are the subject of this review.
PMID- 9635119
TI - Perfluorocarbon induced alterations in pulmonary mechanics.
AB - Perfluorocarbon (PFC) compounds induce pulmonary hyperinflation and respiratory
distress in some animals following intravenous administration. This study was
designed to quantify the effects of two PFC emulsions on lung volumes and
compliance and to identify the mechanism of pulmonary hyperinflation. New Zealand
White rabbits received isotonic saline (3 ml/kg), Fluosol (15 ml/kg) or Oxygent
(90% perfluorooctyl-bromide emulsion, 3 ml/kg). After seven days we measured
functional residual capacity, vital capacity, lung compliance and thoracic gas
volume. Gross and microscopic histologic examination of the lungs was performed.
Functional residual capacity after Fluosol administration was 16.0 +/- 4.0 ml/kg,
significantly greater than after saline (3.4 +/- 1.0 ml/kg) or Oxygent (4.0 +/-
1.4 ml/kg). Vital capacity was lower with Fluosol (30 +/- 5.0 ml/kg) than after
saline (37 +/- 3.0 ml/kg) or Oxygent (37 +/- 2.0 ml/kg). Thoracic gas volume
increased from 9 +/- 1.0 ml/kg (saline) to 16 +/- 13 ml/kg (Oxygent) and 33 +/-
7.0 ml/kg (Fluosol). Lung compliance was the same after saline (1.6 +/- 0.5 ml.cm
H2O-1.kg-1) and Oxygent (1.5 +/- 0.3 ml.cm H2O-1.kg-1) but lower after Fluosol
(0.9 +/- 0.1 ml.cm H2O-1.kg-1). Gross pathology demonstrated foam exudation from
airways of animals receiving PFCs and intra-alveolar foam was identified by light
microscopy. These results show intra-airway foam formation causes gas trapping
and shifts tidal breathing to a less compliant region of the pressure-volume
curve.
PMID- 9635120
TI - Influence of sepsis on the plasma elimination pharmacokinetics of diaspirin
crosslinked hemoglobin in rats.
AB - Septic shock is characterized by abnormalities in microcirculatory O2 delivery
(QO2) and profound tissue O2 debt. Administration of crosslinked hemoglobin may
be a means of augmenting the QO2 and tissue O2 availability. Sepsis is associated
with hemodynamic and metabolic alterations which may affect the pharmacokinetics
of crosslinked hemoglobin. The objective of this study was to determine the
effect of sepsis on the plasma elimination of diaspirin crosslinked hemoglobin
(DCLHb). Twenty-four hours after the induction of sepsis by cecal ligation and
perforation, septic (n = 9) and sham rats (n = 8) received an intravenous
infusion of 300 mg of DCLHb and arterial blood samples were taken at regular
intervals to determine free plasma hemoglobin concentration. DCLHb elimination in
septic and sham rats was consistent with first-order elimination kinetics. The
half life (t1/2) for septic rats was 4.2 +/- 0.7 h and was significantly shorter
than the t1/2 of non-septic rats (5.4 +/- 0.9 h). In all rats, free plasma
hemoglobin returned to basal levels by 24 hours after DCLHb administration. The
volume of distribution for DCLHb in the septic and non-septic rats was not
significantly different and suggests that DCLHb is not influenced by altered gut
permeability. Despite significant changes in some elimination parameters the
differences were small. Consequently, dosing regimens for this compound may not
need to be altered in sepsis.
PMID- 9635121
TI - Accuracy of fluorocrit in determination of blood perflubron concentration.
AB - Previous studies examining the radiosensitizing effects of perfluorochemical
emulsions have based dose recommendations on a measurement known as fluorocrit.
The fluorocrit is the proportion of blood volume occupied by perfluorochemicals
and is measured using standard hematocrit procedures. This measurement is
inherently crude and subject to error and variability between different
individuals measuring the same sample. Furthermore, the fluorocrit method has not
been compared to other quantitative methods to determine its reliability. The
purpose of this study was to compare fluorocrit measurements to those obtained by
gas chromatographic analysis. A 90% w/v perflubron emulsion was administered to
six normal dogs once weekly for four weeks and peripheral blood samples were
obtained at specified time points for analysis. A total of 123 blood samples were
analyzed by both methods. The relationship between blood fluorocrit and plasma
perflubron concentration measured by gas chromatography was examined using
regression models. Based on the modest predictive value (r2 = 0.3683) of the
derived statistical model, we conclude that fluorocrit measurement is an
inaccurate method of estimation of blood perflubron concentration. Caution must,
therefore, be exercised when extrapolating data and dose recommendations from
reports of studies using flurocrit as the only estimate of blood perflubron
concentration.
PMID- 9635122
TI - Proposition of a technique to assess the vasoactive effects of hemoglobin-based
oxygen carrying solutions in vivo: preliminary results in the rabbit aorta.
AB - Most of hemoglobin-based oxygen carriers (HBOCs) increase the blood pressure
after injection in the blood stream by a mechanism involving one or more factors
that contribute to the regulation of the vascular tone. Many techniques make it
possible to study the vascular effects of HBOCs both in vivo and in vitro. The in
vivo methods assess the blood pressure and some estimated regional blood flows
(use of radioactive or colored microspheres). Measurements of the real vessel
diameter and blood flow would be useful to understand hemoglobin-mediated
vasoconstriction mechanism. Our purpose was to elaborate an experimental model in
anesthetized rabbits to monitor the diameter and the blood flow velocity in the
same vessel in order to calculate the absolute blood flow. The blood flow
velocity (in cm/s) was assessed by pulsed Doppler velocimetry and the diameter
(in mm) was assessed by a technique of Wall Tracking. The first results indicate
that the method is well adapted to study the effects of resuscitative fluids
(plasma and blood substitutes) on the aorta vascular tone after hemodilution or
resuscitation from severe hemorrhage.
PMID- 9635123
TI - In vitro osteoinduction of demineralized bone.
AB - Among numerous available materials for osseous repair and reconstruction, those
presenting osteoinductive characteristics and promoting bone regeneration are
preferable. Fresh autologous bone is one of the most effective, but it has some
disadvantages and risks. Demineralized bone matrix (DBM) is considered to be a
valid alternative, because it seems to show osteogenic potential, ascribed to the
presence of bone morphogenetic proteins. In addition it can be prepared without
difficulty and preserved without losing osteoinductive properties. The aim of the
study was to evaluate the osteoinductive ability of xenogenic DBM, by testing DBM
powder obtained from rabbit long bones, in cell culture of murine fibroblasts,
alone or associated with electromagnetic field (EMF), that are known to exhibit
biologic effects on cells: in particular they are used in orthopedics to improve
bone formation. At the end of experiment, alkaline phosphatase (ALP) activity,
calcium levels and cell proliferation and morphology were evaluated. A
statistically significant stimulation of ALP activity and cell proliferation and
a morphological change of fibroblasts were found. The results obtained show how
DBM and EMF have different effects on cells, and that together they have synergic
action toward bone induction.
PMID- 9635124
TI - Preparation of highly purified hemoglobin by affinity elution.
AB - The large scale production of recombinant hemoglobin (Hb) from microorganism or
transgenic hosts for Hb-based blood substitutes places utmost emphasis on purity.
In the present study, a high-resolution, convenient and inexpensive purification
method is developed for purification of Hb from mixtures containing E. coli
extract and bovine serum. This method is based on affinity elution by
pyrophosphate (PPi) of Hb adsorbed on an FPLC column of the anion exchanger
Toyopearl DEAE-650M. Compared to pH elution or NaCl elution, PPi elution makes
possible the preparation of Hb of much higher purity. A procedure combining pH
elution and PPi elution sequentially using a single column proves particularly
valuable. The purification method is also applicable to the purification of
cyanomet-Hb (CNHb+).
PMID- 9635125
TI - Thyroid hormone, all-trans retinoic acid, and 9-cis retinoic acid functioned as
negative modulators of the effect of glucocorticoid on induction of alpha 1-acid
glycoprotein mRNA in RLN-10 cells.
AB - The expression of acute-phase protein genes is controlled by many factors, such
as IL-1, IL-6, glucocorticoids, thyroid hormone (T3), and retinoic acids. We
studied the interaction of T3, glucocorticoids, all-trans retinoic acid (RA), and
9-cis retinoic acid (9cRA) on the expression of the rat alpha 1-acid glycoprotein
(AGP) gene in vitro. Dexamethasone (Dex) activated AGP gene expression in a rat
liver derived cell line, RLN-10. Although T3, RA, and 9cRA by themselves had no
effect on AGP production, they reduced the response to Dex of the AGP gene.
PMID- 9635126
TI - Free radical scavenging activity of fermented papaya preparation and its effect
on lipid peroxide level and superoxide dismutase activity in iron-induced
epileptic foci of rats.
AB - Fermented papaya preparation is a natural health food that has been commercially
sold in Japan for 2 years. It is made by yeast fermentation of Carica Papaya
Linn. We examined the antioxidant action of the fermented papaya preparation on
free radicals and lipid peroxidation. Free radicals have been related with aging
and diseases, such as cancer, diabetes and especially in neurological disorders,
for example, Parkinson's disease or Alzheimer's disease. A diet including
variable antioxidant foods may therefore help to prevent these illnesses. The
free radical scavenging activity of the fermented papaya preparation was examined
using an electron spin resonance (ESR) spectrometer. Fermented papaya preparation
(50 mg/ml) scavenged 80% of hydroxyl radicals (.OH) as spin adducts of spin trap,
5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (5.27 x 10(15)spins/ml) generated by
Fenton reagents. The value of IC50 was 12.5 mg/ml. The oral administration of the
fermented papaya preparation for 4 weeks decreased the elevated of lipid peroxide
levels in the ipsilateral 30 min after injection of iron solution by iron into
the left cortex of rats. The fermented papaya preparation also increased
superoxide dismutase activity in the cortex and hippocampus of them. These
results suggest that the fermented papaya preparation has antioxidant actions and
that it may be prophylactic food against the age related and neurological
diseases associated with free radicals.
PMID- 9635127
TI - Effects of ethanol ingestion on insulin binding to rat Leydig cells.
AB - Effects of ethanol treatment and its withdrawal on insulin binding to isolated
rat Leydig cells were studied. Mature rats were given ethanol by gastric
intubation for 30 days at a dose of 3.0 g/kg body weight, twice daily, as a 25%
(v/v) aqueous solution and treatment was withdrawn for the subsequent 30 days in
an another group. Ethanol treatment markedly increased serum insulin and reduced
the 125I-insulin binding to Leydig cells and the activities of Leydig cellular
steroidogenic enzymes such as 3 beta-HSD and 17 beta-HSD. Withdrawal of ethanol
treatment restored these changed values to their normal levels. The results
suggest the possible involvement of subnormal insulin actions, as that of LH, in
the ethanol-induced impairment of Leydig cellular steroidogenesis and the
resulting hypoandrogenization associated with alcohol abuse.
PMID- 9635128
TI - Attenuated antigenicity of ribonucleoproteins modified by reactive oxygen
species.
AB - Ribonucleoprotein (RNP) particles isolated from fresh goat liver nuclei were
exposed to hydroxyl radical which induced modification in the gross structure of
RNP particles. To evaluate the effect of hydroxyl modification on the antigenic
properties of RNP and possible role of ROS-RNP in the initiation and development
of SLE, enzyme immunoassays were carried out. SLE sera having high titre anti-DNA
antibodies showed enhanced binding to hydroxyl modified RNP particles in
comparison to unmodified RNP particles. In competition assay none of the SLE sera
or isolated IgG showed preference for ROS-modified RNP particles over native RNP
particles. These studies suggest that anti-RNP autoantibodies observed in
subpopulation of SLE patients are generated by some other intra-or extracellular
mechanisms and hydroxyl radical has probably no direct role in the initiation of
antibodies.
PMID- 9635129
TI - Influence of phenoxyherbicides and their metabolites on the form of oxy- and
deoxyhemoglobin of vertebrates.
AB - The effect of phenoxyherbicides and their metabolites on the structure of oxy-
and deoxyhemoglobin was studied by using different doses and times of incubation
of hemoglobin with the herbicide. It was ascertained that among the investigated
hemoglobins the most sensitive was carp oxyhemoglobin incubated with 2,4-D (2,4
dichlorophenoxyacetic acid) and the least sensitive was human hemoglobin.
Comparing the toxicity of 2,4-D, MCPA (2-methyl-4-chlorophenoxyacetic acid), 2,4
DCP (2,4-dichlorophenol), 2,4-DMP (2,4-dimethylphenol) it was found that the
highest decrease occurred in bovine hemoglobin incubated with 2,4-DMP. The
phenoxyherbicides caused stabilization of the structure of T-deoxyhemoglobin in
vitro, in that they decreased the oxygen affinity with a simultaneous increase in
methemoglobin concentration.
PMID- 9635130
TI - Reactivity of the horseradish peroxidase compounds I and II toward organometallic
substrates. A stopped-flow kinetic study of oxidation of ferrocenes.
AB - Reactivity of horseradish peroxidase compounds I and II (HRP-I and HRP-II) toward
organometallicic substrates, viz water-soluble ferrocenes RFc (R = COOH and
CH2NMe2), has been studied at 25 degrees C, pH 6.0 and ionic strength 0.1 M. The
second-order rate constants k2 for the reaction of HRP-I with FcCOOH and
FcCH2NMe2 equal (1.00 +/- 0.04) x 10(6) and (0.27 +/- 0.01) x 10(6) M-1 s-1,
respectively. The values of k3 for the reaction of HRP-II with FcCOOH and
FcCH2NMe2 equal (1.1 +/- 0.1) x 10(4) and (0.25 +/- 0.01) x 10(4) M-1 s-1,
respectively. The steady-state kinetic study of the HRP-catalyzed oxidation of
the ferrocenes by H2O2 under the same conditions gave the second-order rate
constants of (0.94 +/- 0.03) x 10(4) and (0.24 +/- 0.06) x 10(4) M-1 s-1 for
FcCOOH and FcCH2NMe2, respectively, which are in a good agreement with k3. The
results reported here confirm the proposal that the rate-limiting step of the
steady-state oxidation of ferrocenes is the electron transfer from the substrate
to HRP-II.
PMID- 9635131
TI - Starvation induced hypothyroidism involves perturbations in thyroid superoxide
SOD system in pigeons.
AB - This study investigated the influence of starvation over seven days on avian
thyroidal superoxide radical levels and superoxide dismutase activity profiles in
the Indian rock pigeon Columba livia intermeida, in relation with iodine
metabolism. The serum thyroid hormone profile was assayed to correlate the
thyroidal redox status with the circulating thyroid hormone levels. The spin
trapping results suggest a role for thyroidal superoxide anion (O2.-) in causing
a hypothyroid state in pigeons during long term energy withdrawal. Pigeons
starved for 1 day generated superoxide and iodide free radicals in their
thyroids, with a significant decrease in SOD activity. Regain of SOD activity in
2nd- and 3rd-day starved birds is marked by complete scavenging of radicals in
the thyroid, suggesting the significance of SOD in thyroid glands as a potential
antioxidant sink against reactive oxygen species, O2.- Resurgence of O2.-
radicals with a parallel decrease in SOD activity in the thyroid gland on 5th-
and 7th-day of starvation provides evidence of disruption of homeostasis between
pro-oxidant and antioxidant states, leading to oxidative stress in avian thyroid
during long-term calorie crisis. Following starvation both thyroid hormones
thyroxine (T4) and triiodothyronine (T3) decreased, putting pigeons in a
hypothyroid state. We argue that oxidative inactivation of thyroid peroxidase and
other thyroid proteins by radical attack during starvation invoked oxidative
stress, which could be one of the factors responsible for the hypothyroid state
in pigeons.
PMID- 9635132
TI - Reductive dechlorination of DDT to DDD by rat blood.
AB - The present study provides evidence that the reductive dechlorination of DDT (p,
p'-dichlorodiphenyltrichloroethane) to DDD (p, p'-dichlorodiphenyldichloroethane)
mediated by rat blood proceeds in the presence of both a reduced pyridine
nucleotide and a flavin. The reduction appears to proceed in two steps. The first
step is reduction of a flavin such as FAD, FMN or riboflavin by NADPH or NADH,
either enzymatically or nonenzymatically. The second step is nonenzymatic
reductive dechlorination of DDT by the reduced flavin, catalyzed by the heme
group of hemoglobin.
PMID- 9635133
TI - Hormone-induced changes in cardiolipin from Leydig cells: possible involvement in
intramitochondrial cholesterol translocation.
AB - The rate-limiting and hormonally regulated step in steroid hormone biosynthesis
is the delivery of cholesterol from the outer to the inner mitochondrial membrane
where cytochrome P450scc resides. Although the exact mechanism of
intramitochondrial cholesterol translocation remains unknown, the formation of
contact sites between outer and inner mitochondrial membranes appears as a
necessary component for cholesterol transfer. Several pieces of evidence suggest
that local formation of intermembrane contact is a consequence of a non-bilayer
arrangement of polymorphic lipids which are enriched in the junctions. As a step
toward clarifying mitochondrial contact sites formation and thus cholesterol
translocation in steroidogenic cells, we have undertaken studies to identify the
factors which might result in non-bilayer structure to be adopted by
mitochondrial phospholipids on stimulation of MA-10 Leydig cells. Our results
demonstrate that an increase in the unsaturation of the cardiolipin acyl groups
on hormonal stimulation might favor the formation of non-bilayer adhesion points.
PMID- 9635134
TI - Nucleotide sequence and intergeminiviral homologies of the DNA-A of papaya leaf
curl geminivirus from India.
AB - Coat protein gene, rep protein gene and intergenic region of the genome of a
whitefly transmitted geminivirus (WTG) causing severe leaf curl in papaya plants
were PCR amplified, cloned and sequenced. Comparison of the amino acid sequence
of the putative coat protein product of papaya leaf curl virus (PLCV) with some
other mono and bipartite WTGs revealed a maximum of 89.8% homology with Indian
cassava mosaic virus. The genomic organization of PLCV-India is similar to other
WTGs with bipartite genomes. Comparison of the coat protein N-terminal 70 amino
acid sequence (and other biological features) of PLCV with other geminiviruses
shows that PLCV is a distinct geminivirus from India and is related to WTGs from
the old world.
PMID- 9635135
TI - Lucigenin reduction by NADPH-cytochrome P450 reductase and the effect of
phospholipids and albumin on chemiluminescence.
AB - To assess lucigenin, a chemilumigenic probe, as a detector of superoxide anion in
microsomes, NADPH oxidation, lucigenin disappearance, and chemiluminescence in a
system including purified NADPH-cytochrome P450 reductase were examined. NADPH
oxidation was increased by adding lucigenin, and concurrently, its disappearance
and oxygen consumption were also stimulated. Chemiluminescence, which is
negligibly emitted in the presence of the reductase alone, was remarkably
amplified with phospholipids and albumin. Menadione inhibited lucigenin
disappearance resulting in suppression of chemiluminescence. Lucigenin
chemiluminescence measured in microsomes appears not to reflect direct superoxide
anion production from microsomal components and from quinones, such as menadione.
PMID- 9635136
TI - Soluble guanylate cyclase in Saccharomyces cerevisiae.
AB - After removing nonspecific immunoreactivities from crude extract by
immunoaffinity chromatography, an immunoreactive-band at 40kDa of soluble
guanylate cyclase (SGC) from Saccharomyces cerevisiae was detected by Western
blot using rabbit anti-beta 1 subunit of SGC. Cyclic GMP level and SGC activity
was measured by ELISA. Immunoprecipitated yeast SGC was activated by sodium
nitroprusside, whereas inhibited by 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one.
Increased cyclic GMP level was also noted when intact yeast cells were incubated
with s-nitrosoglutathione, a NO donor. The result implies that NO can be utilized
intracellularly and extracellularly. Moreover, the presence of SGC suggests the
significance of NO/cyclic GMP signaling in unicellular eukaryotes.
PMID- 9635137
TI - Methionine modification impairs the C5-cleavage function of cobra venom factor
dependent C3/C5 convertase.
AB - The complement-mediated lysis of guinea pig erythrocytes by cobra venom factor
(CVF) decreased by 50-60% within 2 min of treatment with 5 mM sodium periodate at
0 degree C. This loss of activity paralleled modification of 3-4 Met; other amino
acids and sugar residues of the oligosaccharide chains were not affected.
Treatment with N-chlorosuccinimide or chloramine-T under conditions that
specifically modified 3-4 readily-oxidizable Met also caused 50-60% loss of CVF
activity. The secondary structure of CVF was not altered by these modifications.
Methionine-modified CVF (MetCVF) supported the cleavage of factor B by factor D
with equal efficiency as that of untreated CVF to form C3/C5 convertase
(MetCVF,Bb) of the alternative pathway. MetCVF,Bb and CVF,Bb were
indistinguishable with respect to C3 cleavage. However, the C5-cleavage ability
of MetCVF,Bb was significantly lower than that of CVF,Bb. These results suggest
the involvement of Met in CVF binding of C5.
PMID- 9635138
TI - DNA methylation by wheat cytosine DNA methyltransferase: modulation by protease
inhibitor E-64.
AB - Cytosine DNA methyltransferase isolated from wheat seedlings and purified in the
presence of metalloprotease and serine protease inhibitors has molecular mass and
specific activity equal to about 85 kDa and 250 units/mg protein, respectively.
Apparent K(m) for AdoMet and [I]50 for AdoHcy values are about 6 microM and 12
microM, respectively. The enzyme is active in wide pH range (pH 5.5-8.5) and is
inhibited by NaCl. The enzyme rapidly loses its methyltransferase activity in the
absence of substrates. Using the cysteine protease inhibitor E-64 it has been
shown that rapid enzyme inactivation is caused by disappearance of essential
enzyme SH-groups but is not due to proteolytic enzyme cleavage.
PMID- 9635139
TI - A novel method for selection of chymotrypsin inhibitors from a phage peptide
library.
AB - A novel screening strategy has been developed for the identification of alpha
chymotrypsin inhibitors from a phage peptide library. In this strategy, the
standard affinity selection protocol was modified by adding a proteolytic
cleavage period to avoid recovery of alpha-chymotrypsin substrates. After four
cycles of selection and further activity assay, a group of related peptides were
identified by DNA sequencing. These peptides share a consensus sequence motif as
(S/T)RVPR(R/H). Then, a corresponding short peptide (Ac-ASRVPRRG-NH2) was
synthesized chemically and proved to be an inhibitor of alpha-chymotrypsin. The
present work provides a useful way for searching proteinase inhibitors without
detailed knowledge of the molecular structure.
PMID- 9635140
TI - The prevention of carbon tetrachloride-induced hepatotoxicity in mice by alpha
hederin: inhibiton of cytochrome P450 2E1 expression.
AB - The protective effects of alpha-Hederin on carbon tetrachloride-induced
hepatotoxicities were investigated in mice. Pretreatment with alpha-Hederin prior
to the administration of carbon tetrachloride significantly prevented the
increase in serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH)
activity and lipid peroxidation in a dose dependent manner. Hepatic glutathione
levels and glutathione-S-transferase activities were not affected by pretreatment
with alpha-Hederin alone but pretreatment with alpha-Hederin protects carbon
tetrachloride-induced depletion of hepatic glutathione levels. The effects of
alpha-Hederin on the cytochrome P450 (P450) 2E1, the major isozyme involved in
carbon tetrachloride bioactivation were investigated. alpha-Hederin markedly
decreased the P450 2E1-specific activities of p-nitrophenol and aniline
hydroxylation in a dose-dependent manner. Consistent with these observations, the
P450 2E1 expressions were also decreased, as determined by immunoblot analysis.
These results demonstrate that treatment of mice with alpha-Hederin decreases the
expression and activities of P450 2E1 enzyme, and reduces biotransformation of
carbon tetrachloride, and diminished carbon tetrachloride-induced liver injury.
PMID- 9635141
TI - Hydrogen peroxide-supported activities of semisynthetic flavocytochrome 2B4.
AB - Semisynthetic flavocytochromes, obtained by covalent binding of riboflavin with
cytochromes P450 2B4, were able to catalyze the H2O2-mediated reactions of
aniline p-hydroxylation, aminopyrine N-demethylation and p-nitroanizole' O
dealkylation. The rates of the flavocytochrome-catalyzed, H2O2-supported
reactions far exceeded those of the appropriate NADH-dependent reactions and were
comparable with the cytochrome P450 2B4-catalyzed, peroxide-mediated reaction
rates. The kinetic parameters (kcat, K(m)) for the peroxide-dependent
flavocytochrome P450 2B4 reactions were obtained. Sodium cyanide and SKF-525A, a
specific P450 inhibitor, were both shown to inhibit these reactions. The
generation of active oxygen species by flavocytochrome 2B4 was registered by
chemiluminescence intensity.
PMID- 9635142
TI - A novel rapid-reaction spectrophotometric method for monitoring monovalent anion
exchange by human erythrocyte band 3.
AB - Thiocyanate (SCN-) uptake into human erythrocytes and resealed ghosts was
measured by monitoring the intracellular reaction of SCN- with methemoglobin
using a dual wavelength stopped-flow apparatus. The cellular reaction was
considerably slower than the reaction of SCN- with methemoglobin in solution,
indicating that SCN- diffusion and not chemical reaction was rate limiting. This
view was confirmed by showing that the uptake rate followed saturation kinetics
(K(m) approximately 9 mM), thus indicating that SCN- transport involves a
facilitated diffusion process. Addition of DIDS (4,4'-diisothiocyanatostilbene
2,2'-disulfonate) totally inhibited SCN- uptake, thus identifying band 3 as the
sole facilitator. Substitution of iodide or sulfate for trans chloride, slowed
SCN- uptake by 4-fold and 35-fold respectively. Reducing the trans chloride
concentration from 150 to 2 mM decreased the extent of the reaction, and slowed
the observed rate by about 2-fold. These results define a new approach for the
continuous monitoring of monovalent anion exchange by human erythrocyte band 3.
PMID- 9635143
TI - Luminol luminescence induced by oxidants in antioxidant-deficient yeasts
Saccharomyces cerevisiae.
AB - Luminol chemiluminescence induced in the presence of yeast cells and yeast cell
homogenates was significantly induced by exogenous oxidants (hydrogen peroxide
and menadione). tert-Butyl hydroperoxide did not stimulate chemiluminescence by
itself but augmented menadione-induced chemiluminescence. Comparison of yeast
strains deficient in catalase, superoxide dismutase or glutathione showed that
only glutathione-deficient strains showed elevated chemiluminescence in this
system. These results support the idea that more reactive species than hydrogen
peroxide and superoxide are critical in the induction of luminol
chemiluminescence.
PMID- 9635144
TI - Cloning and sequencing of the cDNA coding for pig pre-uteroglobin/Clara cell 10
kDa protein.
AB - Using reverse transcription-polymerase chain reaction (RT-PCR) on pig lung mRNAs,
we have cloned and sequenced an almost full-length complementary DNA (cDNA)
coding for pig pre-uteroglobin/Clara cell 10 kDa protein (UG/CC10), a major
secretory protein of lung Clara cells. The deduced amino acid sequence indicated
a preprotein of 91 residues, 21 of which corresponded to the signal peptide.
Comparison of the sequence with those of known pre-UG/CC10 from other species
indicated that the pig protein resembles the structure shared by human and
Lagomorpha pre-UG/CC10 but differ from the proteins from Rodentia that are
composed of 96 aminoacids and contain signal peptides of 19 residues. Some amino
acids, that form part of a hydrophobic pocket inside the mature protein, are well
conserved in all UG/CC10 suggesting an important function of this cavity.
Northern analysis indicated that pig UG/CC10 mRNA is abundant in lung but is not
detectable in liver, uterus or epididymis. The results are discussed in relation
to a possible physiological function of UG/CC10.
PMID- 9635145
TI - The 1997 Stevenson Award Lecture. Cardiac K+ channel gating: cloned delayed
rectifier mechanisms and drug modulation.
AB - K+ channels are ubiquitous membrane proteins, which have a central role in the
control of cell excitability. In the heart, voltage-gated delayed rectifier K+
channels, like Kv1.5, determine repolarization and the cardiac action potential
plateau duration. Here we review the broader properties of cloned voltage-gated
K+ channels with specific reference to the hKv1.5 channel in heart. We discuss
the basic structural components of K+ channels such as the pore, voltage sensor,
and fast inactivation, all of which have been extensively studied. Slow, or C
type, inactivation and the structural features that control pore opening are less
well understood, although recent studies have given new insight into these
problems. Information about channel transitions that occur prior to opening is
provided by gating currents, which reflect charge-carrying transitions between
kinetic closed states. By studying modulation of the gating properties of K+
channels by cations and with drugs, we can make a more complete interpretation of
the state dependence of drug and ion interactions with the channel. In this way
we can uncover the detailed mechanisms of action of K+ channel blockers such as
tetraethylammonium ions and 4-aminopyridine, and antiarrhythmic agents such as
nifedipine and quinidine.
PMID- 9635146
TI - Extravascular adenosine influences endothelium-derived nitric oxide release from
perfused dog semitendinosus artery.
AB - We tested the hypothesis that extravascular adenosine induces the release of
vasodilatory products from endothelial cells lining skeletal muscle vessels.
Endothelium-intact (n = 35) and -denuded (n = 5) dog semitendinosus intramuscular
arteries were isolated, cannulated, and placed in 100-mL baths containing Krebs
Henseleit bicarbonate buffer (Krebs) at 37 degrees C and gassed with 95% O2--5%
CO2. Each vessel, as well as a parallel tubing segment (avascular control), was
perfused at 3.5 +/- 0.2 mL/min (inflow pressure 94 +/- 2 mmHg; 1 mmHg = 133.3 Pa)
with Krebs containing 100 microM phenylephrine, 6% dextran, and 15 units/mL
superoxide dismutase. Perfusate from all segments dripped onto endothelium
denuded dog femoral artery rings. The addition of 10 microM acetylcholine to the
perfusate to test the functional integrity of endothelium-intact donor segments
did not alter resistance in vessel segments or change force in rings. The
addition of 100 microM adenosine to the extravascular bath decreased resistance
1.5 +/- 0.4 mmHg.mL-1.min-1 in vessel segments but was without effect on
downstream rings. When acetylcholine was retested in the presence of
extravascular adenosine, a relaxation (16 +/- 6%) occurred in rings receiving
perfusate from endothelium-intact segments but not endothelium-denuded or tubing
segments. This relaxation was eliminated by N omega-nitro-L-arginine (10 microM),
a nitric oxide synthase inhibitor, and was attenuated to 4 +/- 1% by 8
phenyltheophylline (10 microM), an adenosine receptor antagonist. Thus adenosine,
in conjunction with acetylcholine, acting through a receptor-mediated event,
resulted in the release of nitric oxide from the endothelium of perfused
intramuscular arteries, indicating the potential for extravascular conditions to
influence the release of endothelium-derived products.
PMID- 9635147
TI - Scavestrogen sulfamates: correlation between estrone sulfatase inhibiting and
antioxidant effects.
AB - In the present study estrone sulfatase (steryl-sulfatase; EC 3.1.6.2) and
phenylsulfatase (arylsulfatase B; EC 3.1.6.1) inhibiting as well as antioxidant
effects exerted by ring B,C unsaturated sulfamates of estrone (J 1025), 17 beta
estradiol (J 1054, J 1059, J 1067), and 17 alpha-estradiol (J 1051, J 1064, J
1065) were examined as compared with their parent compounds, J 994, J 995, and J
1050, using six different in vitro models: (i) estrone sulfatase activity in
human placental microsomes, (ii) phenylsulfatase activity isolated from Helix
pomatia, (iii) Fenton reaction driven lipid peroxidation in rat synaptosomes,
(iv) Fe(II)-chelating activities, (v) formation of superoxide anion radicals, and
(vi) total antioxidative activities. Ring B,C unsaturated estrogen (so-called
scavestrogen) sulfamates were found to act as potent inhibitors of the following
enzyme activities and generated radicals: estrone sulfatase, phenylsulfatase,
lipid peroxyl, and superoxide anion. In addition, scavestrogen sulfamates were
able to influence the iron redox chemistry and total antioxidative activities.
These findings indicate that relatively minor modifications in the chemical
structure of classical steroid sulfamates can preserve or enhance their estrone
sulfatase inhibiting properties and, simultaneously, amplify their antioxidant
capacity to a great extent. Taken together, our data suggest that scavestrogen
sulfamates such as J 1025, J 1051, or J 1054 (17 beta-dihydroequilenin sulfamate)
may serve as a very promising basis for the development of steroid-derived
estrone sulfate-sulfatase inhibitors characterized by promising estrone sulfatase
inhibiting activities in combination with a "good" antioxidant potency.
PMID- 9635148
TI - Functional effects of uridine triphosphate on human skinned skeletal muscle
fibers.
AB - Chemically skinned human skeletal muscle fibers were used to study the effects of
uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and
release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of
adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship
to the left along the abcissae and increased maximum Ca(2+)-activated tension,
both effects being larger in slow- than in fast-type fibers; (ii) markedly
reduced Ca2+ uptake by the SR (evaluated by the caffeine-evoked tension) in both
fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive
Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow-
but not in fast-type fibers. The effects on the SR functional properties are
consistent with the notion that UTP is a poor substitute for ATP as a substrate
for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca(2+)
release channel. The UTP-induced tension in human slow-type fibers is attributed
to effect(s) of the nucleotide on the tension-pCa relationship of the contractile
machinery. The present data reveal important differences between the effects of
UTP on human versus rat muscle fibers.
PMID- 9635149
TI - Thromboxane A2 does not act at the carotid sinus to mediate cardiovascular,
adrenocorticotropin, cortisol, or blood gas responses.
AB - Thromboxane A2 (TxA2), well known as a vasoconstrictor and activator of
platelets, also stimulates reflex cardiovascular, pituitary, adrenocortical, and
blood gas responses, although the site of action is unknown. Previously we
determined that the site of these actions is perfused by the carotid vasculature.
The purpose of the present study was to test the hypothesis that TxA2 stimulates
these responses by acting at the carotid sinus. The TxA2 mimetic U46619 (1
microgram.kg-1.min-1) or saline was infused into the carotid artery (CA) or vena
cava in conscious, chronically instrumented carotid sinus denervated (CSD) or
sham-operated sheep. Mean arterial pressure increased in all groups receiving
U46619. Heart rate increased only in the CSD group receiving CA infusions of
U46619. Adrenocorticotropic hormone (ACTH) and cortisol increased in the sham and
CSD groups receiving CA U46619, and responses were not different between sham and
CSD groups. PaCO2 values were higher in all CSD treatment groups compared with
sham treatment groups. Arterial pH increased and PaCO2 decreased in both the sham
and CSD groups in response to CA U46619. Although PaCO2 values were higher
overall in the CSD group, the magnitude of change in response to U46619 infusions
was similar in sham and CSD animals. There was no difference in pHa between CSD
and sham groups. Hematocrit and PaO2 did not change. We conclude that TxA2 does
not act at the carotid sinus, as responses to U46619 infusions in CSD animals
were not different in the cases of ACTH, cortisol, and blood gases, or were
enhanced rather than diminished in the case of heart rate. These findings support
a hypothesis that TxA2 acts at the brain to mediate cardiovascular, pituitary,
adrenocortical, and blood gas responses.
PMID- 9635150
TI - Similarities between vasoconstrictor- and veratridine-stimulated metabolism in
perfused rat hind limb.
AB - The vasoconstrictors norepinephrine (NE) and angiotensin II (AII) mediate
increases in oxygen uptake (VO2) by the constant flow perfused rat hind limb that
are inhibited by quinidine-like membrane-stabilizing effects (involving the
interruption of action potential) of (+/-)-propranolol with little effect on
vasoconstriction. The membrane labilizer veratridine, 10 microM, which has the
capability of maintaining voltage-gated Na+ channels of the plasma membrane in
their open state, also increases VO2 but without an increase in pressure. Thus in
the present study veratridine was characterized in detail and compared with NE in
the same system. Veratridine (3-100 microM) produced a dose-dependent stimulation
of VO2 (from 11.8 +/- 0.3 to 20.4 +/- 0.6 mumol.h-1.g-1 (n = 5), p < 0.0001) and
lactate efflux (LE) (from 7.4 +/- 0.6 to 23.0 +/- 4.7 mumol.h-1.g-1 (n = 5), p <
0.01). These increases were independent of vasoconstriction at low doses (< or =
10 microM). At higher doses of veratridine the accompanying minor
vasoconstriction (from 17 +/- 1 to 30 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 5), p <
0.005) was blocked by sodium nitroprusside (NP) while neither VO2 nor LE was
greatly affected. Low Na+ perfusions (25 mM) did not affect the vasoconstrictor
action of NE but markedly inhibited increases in VO2 and LE due to either
veratridine or NE. Veratridine (10 microM) mediated increases in VO2 and LE were
blocked by either (+/-)-propranolol (100 microM) or 150 microM quinidine. It is
concluded that vasoconstrictors such as NE, which stimulate VO2 in the perfused
rat hind limb, do so by a two-stage process involving an essential nitroprusside
sensitive redirection of flow followed by a mechanism involving increased ion
movement across skeletal muscle cell membranes, which is blocked by membrane
stabilizers. Veratridine achieves a similar increase in VO2 but may do so by
directly destabilizing the skeletal muscle cell membrane without the requirement
of a redirection of flow.
PMID- 9635151
TI - Inhibitory effects of candesartan on responses to angiotensin peptides in the
hindquarters vascular bed of the cat.
AB - The effects of the nonpeptide angiotensin II AT1 receptor antagonist candesartan
on responses to angiotensin II were investigated in the hindquarters vascular bed
of the cat. Under constant-flow conditions, injections of angiotensin II into the
hindquarters perfusion circuit elicited dose-dependent increases in perfusion
pressure. Candesartan in a dose of 3 micrograms/kg i.v. decreased vasoconstrictor
responses to angiotensin II in a competitive manner. However, at doses of 10-1000
micrograms/kg i.v., candesartan shifted the dose-response curve to angiotensin II
to the right in a nonparallel manner, suggesting a noncompetitive blockade. The
inhibitory effects of candesartan on responses to angiotensin II were long in
duration, and the AT1 receptor antagonist had little effect on baseline
pressures. Candesartan was without effect on vasoconstrictor responses to
norepinephrine, U46619, PGF2 alpha, and BAY K8644; on biphasic responses to
endothelin-1; and on vasodilator responses to acetylcholine. Candesartan
significantly attenuated hindquarters vasoconstrictor responses to angiotensin
III and IV with a parallel shift at the 3 micrograms/kg iv dose and a nonparallel
shift to the right at the high dose of the AT1 receptor antagonist. The results
of the present study indicate that candesartan is a potent angiotensin AT1
receptor antagonist that can induce both competitive and noncompetitive blockade
of responses to angiotensin II, III, and IV n the hindquarters vascular bed of
the cat.
PMID- 9635152
TI - Analysis of effects of bosentan (Ro 47-0203), a nonpeptide endothelin ETA/ETB
receptor antagonist, in the hind-limb vascular bed of the cat.
AB - The effects of bosentan (Ro 47-0203), an endothelin A and B receptor antagonist,
on responses to endothelin-1, sarafotoxin 6c, angiotensin II, and arginine
vasopressin were investigated in the hind-limb vascular bed of the cat. Under
constant-flow conditions, intraarterial injections of endothelin-1 and
sarafotoxin 6c induced biphasic changes in hind-limb perfusion pressure
characterized by an initial decrease followed by a secondary increase in
perfusion pressure. The vasodilator and vasoconstrictor components of the
biphasic responses to endothelin-1 and sarafotoxin 6c were reduced by bosentan,
and the endothelin receptor antagonist reduced baseline systemic arterial and
hind-limb perfusion pressures. Bosentan decreased vasoconstrictor responses to
lower doses of angiotensin II, whereas responses to higher doses of angiotensin
II and responses to vasopressin, U46619, BAY K8644, norepinephrine,
acetylcholine, bradykinin, levcromakalim, PGE1, adrenomedullin, and calcitonin
gene-related peptide were not altered. Vasoconstrictor responses to ET-1 were not
altered by the angiotensin AT1 receptor antagonist DuP 532 or the AT2 receptor
antagonist PD123,319. The results of the present study show that bosentan
attenuates vasodilator and vasoconstrictor responses to endothelin-1 and
sarafotoxin 6c and vasoconstrictor responses to lower doses of angiotensin II in
the hind-limb vascular bed of the cat. These results suggest that endothelin may
be involved in mediating responses to lower doses of angiotensin II and in the
maintenance of baseline tone in the systemic vascular bed of the cat.
PMID- 9635153
TI - Changes in [K+]o evoked by baclofen in guinea pig hippocampus.
AB - K(+)-sensitive microelectrodes were used to record changes evoked by baclofen in
extracellular potassium concentration ([K+]o) and field potentials in the stratum
pyramidale (SP) and stratum radiatum (SR) in the CA1b region of guinea pig
hippocampal slices in vitro. Bath applications of (+/-)-baclofen (1 microM-3 mM
for approximately 5 min) evoked changes in [K+]o, which were in most cases
sustained throughout agonist application and reversed during washout. The maximal
(Rmax) values for curves fitted to the concentration-response data were for SP
and SR, respectively, 0.59 +/- 0.03 and 0.65 +/- 0.03 mM, and EC50 values were
39.7 and 39.4 microM, respectively. The evoked K+ and field potential changes
were significantly correlated and could be blocked by 2-OH-saclofen (50 microM)
and CGP 35348 (50 microM). In < or = 10% of experiments baclofen (10-50 microM)
induced either a decrease or a transient increase (< or = 1 min duration) in
[K+]o; in some slices with concentrations > or = 20 microM an initial decrease
preceded a progressive increase. Pressure ejection of baclofen (100 microM for
100-900 ms) evoked increases in [K+]o and field potentials, which were larger in
SR than in SP. In < or = 10% of slices brief and (or) sustained application of
baclofen (by either bath perfusion or pressure ejection) also evoked synchronous,
repetitive interictal and ictal discharges at frequencies approximately 1/s and
1/12 s, respectively, an observation that affirms a proconvulsant capacity. It is
concluded that (i) although increases in [K+]o evoked by baclofen in SR compared
with SP are slightly larger, they are not significantly different, (ii) GABAB
receptor subtype(s) in SR and SP appear similar, as they have identical
affinities, and (iii) [K+]o accumulations evoked by GABA likely include a
contribution from a GABAB receptor activated K+ conductance, especially in
dendritic regions.
PMID- 9635154
TI - Gentamicin uptake by LLCPK1 cells: effect of intracellular and extracellular pH
changes.
AB - The mechanisms by which aminoglycosides are transported across the luminal
membrane of renal proximal tubular cells remain unclear. A luminal organic
cation/H+ exchange as well as an adsorptive endocytosis membrane process has been
proposed to be involved in gentamicin renal accumulation. The objectives of this
work were to explore further the effects of intracellular and extracellular pH
changes on gentamicin uptake. [3H]Gentamicin uptake by a continuous renal
epithelial cell line, LLCPK1, grown as a monolayer on an impermeable surface was
measured at different temperatures and pH conditions and in the presence of
various inhibitors. Uptake of gentamicin was found to be carrier mediated (K(m) =
1.26 +/- 0.22 mM, Vmax = 289 +/- 27 pmol.mg-1.min-1), energy dependent (inhibited
in part by sodium azide), and temperature dependent (37 degrees C > 4 degrees C).
Fifteen-minute gentamicin (10 microM) uptake was inhibited by 1 mM of the organic
cations cimetidine (61.0%), quinidine (73.5%), quinine (68.6%), and verapamil
(61.5%). More importantly, while an outwardly directed proton gradient did not
have a significant effect on gentamicin uptake, extracellular acidification (pH
6.5), which leads to a higher degree of gentamicin ionization, significantly
enhanced gentamicin uptake by LLCPK1 monolayer cells. These results suggest that
the luminal organic cation/H+ exchanger is not involved in gentamicin uptake by
renal cultured epithelial cells. Rather, the cationic charge of gentamicin
appears to be one of the primary determinants for renal luminal uptake.
PMID- 9635155
TI - Acute effects of prolactin on passive calcium absorption in the small intestine
by in vivo perfusion technique.
AB - The acute effect of intraperitoneally administered prolactin (0.2, 0.4, and 0.6
mg/kg body weight) on passive calcium transport in duodenum, proximal jejunum,
and ileum of sexually mature female Wistar rats was investigated by using an in
vivo perfusion technique. Test solution containing (in mM) NaCl, 100; KCl, 4.7;
MgSO4, 1.2; CaCl2, 20; D-glucose, 11; sodium ferrocyanide (Na4Fe(CN)6), an index
of net water transport, 20; and 0.7 microCi 45CaCl2 (1 Ci = 37 GBq) was perfused
through the 10-cm intestinal loop for 60 min. Results showed that 0.4 mg
prolactin/kg body weight significantly increased duodenal net Ca absorption (net
Ca) from 23.81 +/- 1.84 to 30.56 +/- 1.57 mmol/g dry weight (p < 0.05) by
stimulating the lumen to plasma calcium flux (CaL-P). The jejunum responded to
0.2, 0.4, and 0.6 mg prolactin/kg body weight by reversing from net Ca absorption
of 18.60 +/- 1.70 mmol/g dry weight to net secretion of -3.30 +/- 1.56, -10.39 +/
2.21, and -11.79 +/- 2.04 mmol/g dry weight (p < 0.01), respectively, as a
result of a dose-dependent increase in plasma to lumen calcium flux (CaP-L).
Calcium fluxes in the ileum on the other hand did not respond to prolactin. There
was a close correlation between net water flux and net calcium flux in all three
intestinal segments under basal condition regardless of the luminal sodium
concentration. However, this correlation was lost after prolactin administration,
which while having no effect on net water flux, altered the duodenal and jejunal
calcium fluxes. By varying the luminal concentration of sodium, it was found that
the stimulatory effect of 0.4 mg prolactin/kg body weight on the duodenal CaL-P
was reduced when compared with control, i.e., 17.84 +/- 0.91 vs. 26.64 +/- 1.05
mmol/g dry weight at a sodium concentration of 180 mM, and 14.48 +/- 0.99 vs.
20.12 +/- 1.34 mmol/g dry weight at a sodium concentration of 140 mM. At a sodium
concentration of 80 mM, the prolactin effect was absent. Since duodenal Na(+)-K+
ATPase activity was increased by prolactin from 3.77 +/- 0.16 to 4.95 +/- 0.30
mumol Pi.mg-1 protein.h-1 (p < 0.05), sodium dependency of the prolactin-enhanced
lumen to plasma calcium flux may be related to both sodium-induced water flow and
calcium-sodium exchange across the basolateral membrane. Thus, it was postulated
that under basal condition, net calcium transport in the small intestine occurred
with the sodium-induced water transport along the paracellular pathway. However,
after prolactin administration, this association was lost. Prolactin-enhanced
lumen to plasma calcium flux in the duodenum was sodium dependent and involved
the Na(+)-K+ ATPase activity. In the proximal jejunum, prolactin stimulated
plasma to lumen calcium flux, but the mechanism was not known.
PMID- 9635156
TI - Muscarinic inhibition of substance P induced ion secretion in piglet jejunum.
AB - We examined the effects of the muscarinic agonist carbachol on ion secretion
induced by substance P (SP) in piglet jejunal tissues mounted in Ussing chambers.
Tetrodotoxin was present in all solutions to inhibit neural activity. Carbachol
added 10 min prior to 0.75 microM SP dose dependently inhibited subsequent SP
responses, with 90% inhibition at 10 microM carbachol. Addition of an equipotent
dose of SP (7.5 microM) had no effect on subsequent carbachol-induced secretion.
Carbachol's inhibition of SP-induced secretion was evident for at least 45 min
and was abolished by prior addition of the M3 receptor antagonist 4
diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), but remained intact in
the presence of the M2 antagonist gallamine or the nicotinic antagonist
mecamylamine. Atropine added 10 min after carbachol restored subsequent SP
responses toward control levels. Carbachol also reduced secretory responses to
histamine and, to a lesser extent, prostaglandin E2 (PGE2). SP-induced secretion
was not affected by prior addition of histamine and was reduced by PGE2 only at
the highest PGE2 concentration. The results suggest that activation of the
epithelial M3 receptor by carbachol inhibits subsequent secretory responses to
the calcium-mediated agonists SP and histamine in piglet jejunum. This may
reflect muscarinic activation of a negative messenger in epithelial cells that
limits Cl- secretion.
PMID- 9635157
TI - Antigen-induced responses in lung parenchymal strips during sinusoidal
oscillation.
AB - We have recently demonstrated that tissue resistance increases during the early
response to antigen challenge in sensitized Brown-Norway rats. The purpose of the
present study was to investigate in vitro the dynamic tissue response to antigen
challenge and the involvement of the mediators, i.e., serotonin (5HT) and
leukotriene D4 (LTD4). In addition, we questioned whether strips from sensitized
rats responded differently to nonspecific challenge compared with those of
unsensitized controls. We sensitized Brown-Norway rats with ovalbumin and
performed experiments using strips of subpleural parenchyma. Tissue strips were
challenged with ovalbumin in the bath; in some experiments the tissues were
exposed to methysergide (10(-6) M), a 5HT antagonist, or MK-571 (10(-6) M), a
LTD4 receptor antagonist, or both, prior to challenge. At the end of the
experiment all tissues were exposed to carbacholine (10(-3) M). Oscillation
mechanics of tissue strips were studied and values of resistance (R), elastance
(E), and hysteresivity (eta) were obtained. During ovalbumin challenge in
sensitized tissues, R, E, and eta increased significantly (% change in R, 12.1 +/
2.1%; % change in E, 3.8 +/- 1.3%; % change in eta, 9.3 +/- 2.8%). Both
methysergide and MK-571 reduced the increase in R (3.0 +/- 0.6 and 3.2 +/- 0.8%,
respectively, p < 0.05 vs. ovalbumin). There was no difference between sensitized
and unsensitized strips in the response to carbacholine challenge. These data
suggest that the oscillatory behaviour of tissue strips from sensitized rats is
altered after ovalbumin challenge. The mechanism of that response is mediated by
both 5HT and LTD4.
PMID- 9635158
TI - Effect of endothelium removal on prostaglandin and nitric oxide function in
pulmonary resistance arteries in the lamb.
AB - We have recently shown that isolated pulmonary resistance arteries of the fetal
lamb have prostaglandin (PG) I2 based and nitric oxide (NO) based relaxing
mechanisms, which are activated by oxygen (at neonatal levels) and bradykinin.
The present study was carried out to ascertain whether these mechanisms remain
operational after removal of the endothelium. Endothelium-denuded vessels pre
equilibrated at a neonatal Po2 were not affected by indomethacin (2.8 microM),
while they contracted weakly to NG-nitro-L-arginine methyl ester (L-NAME, 100
microM). However, the latter response did not reach significance and resembled
that of intact vessels at fetal Po2. Bradykinin (0.1-100 nM) dose dependently
(from 1-3 nM upwards) relaxed endothelium-denuded arteries that had been
precontracted with a thromboxane (TX) A2 analog (ONO-11113, 0.1 microM) or excess
potassium (5 mM Ca2+ in K(+)-Krebs) at a neonatal Po2. The response was the same
under the two conditions, but it was smaller than that of intact arteries.
Bradykinin relaxation of ONO-11113-contracted arteries was completely or nearly
completely inhibited by indomethacin and L-NAME. We conclude that endothelium
denuded, pulmonary resistance arteries maintain PG (conceivably PGI2) mediated
and NO-mediated relaxing mechanisms. These extra-endothelial mechanisms are
activated by bradykinin but not by oxygen.
PMID- 9635159
TI - Presence of NK1 receptors on a mucosal-like mast cell line, RBL-2H3 cells.
AB - Reverse transcription--polymerase chain reaction of mRNA from rat RBL-2H3 cells
yielded a 316 base pair band consistent with that predicted for the neurokinin-1
(NK1) receptor. Saturation and competition binding with 125I-labeled Bolton
Hunter substance P, substance P fragments, and a series of selective tachykinin
receptor agonists and antagonists demonstrated that RBL-2H3 cells express high
affinity binding sites for substance P on their surfaces with the kinetic and
pharmacological properties of NK1 receptors. The pharmacology of these 125I
labeled substance P binding sites was (from most to least potent)
[Sar9,Met(O2)11]substance P > substance P 4-11 >> GR82334 << MEN 10,376. However,
substance P 1-4, substance P 8-11, substance P 9-11, and [Trp7, beta
Ala8]neurokinin A 4-10 failed to compete for binding. The metabolically stable
NK1 receptor agonist, [Sar9,Met(O2)11] substance P, caused a 49% increase in 5
hydroxytryptamine release above basal levels. The results demonstrate the
presence of functional NK1 receptors on RBL-2H3 cells, a mucosal-like mast cell
line.
PMID- 9635160
TI - Electrical conduction within the cerebrovasculature of stroke-prone spontaneously
hypertensive rats.
AB - Alterations in electrical conductivity between smooth muscle cells (SMCs) can
alter the spread and effectiveness of electromechanical SMC contraction. We
attempted to determine whether alterations in pressure-dependent constriction
(PDC) occurring in relation to stroke development within the middle cerebral
arteries (MCAs) of Wistar-Kyoto stroke-prone hypertensive rats (SHRsp) were
associated with changes in electrical conductivity between the SMCs. Current was
injected into nonpressurized MCAs, using a suction electrode. The conducting
distance along the length of the MCA where the amplitude of the membrane
potential deflection (electronic potential) produced by current injection
declined to 1/e (length constant) was used to measure conductivity. PDC to a 100
mmHg pressure step was measured with a pressure myograph. A loss of PDC in the
MCAs of SHRsp preceded stroke development. Heptanol (4 mM), a gap junction
communication inhibitor, reversibly inhibited conductivity and PDC in the MCA of
prestroke SHRsp. The ability of heptanol to reversibly inhibit PDC was likely not
related to it's ability to alter electrical conduction. The length constant of
electrical conduction in the MCAs was about 0.75 mm and didn't differ between MCA
sampled from pre-versus post-stroke SHRsp or Sprague-Dawley rats. It was
concluded that alterations in electrical conductivity along the MCA could modify
the spread of PDC, but such changes do not contribute to the loss of PDC within
the MCA of poststroke SHRsp.
PMID- 9635161
TI - Plasma and lipoprotein lipid composition and hepatic antioxidant status in
spontaneously hypertensive (SHR) and normotensive (WKY) rats.
AB - Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant
status were investigated in hypertensive, 14-week-old spontaneously hypertensive
(SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat
chow. Total plasma calcium and magnesium concentrations were similar between both
rat strains; however, systolic blood pressure in SHR was greater than in WKY at
13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg; p < or = 0.05), confirming
hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations
were lower (p < or = 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL
cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio
compared with WKY counterparts. No significant differences in the relative
proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY.
Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than
WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat
liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione
peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were
similar in SHR and WKY counterparts. A possible compensatory effect to the
oxidative status of SHR was suggested by the significant (p < 0.05) increase in
both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities.
Despite these results, in vitro oxidative challenge studies with H2O2
demonstrated a greater susceptibility of liver to GSH depletion in the SHR,
although no parallel change in thiobarbituric acid reactive substances (TBARS)
production was observed. The comparatively lower plasma cholesterol observed in
hypertensive SHR paralleled specific differences in liver catalase and
glutathione redox antioxidant enzyme activities.
PMID- 9635162
TI - Effects of a selective phosphodiesterase IV inhibitor (CDP-840) in a leukotriene
dependent non-human primate model of allergic asthma.
AB - The activity of CDP-840, a novel, selective phosphodiesterase IV inhibitor was
determined in a leukotriene-dependent non-human primate model of allergic asthma.
Measurements of specific airway resistance (sRaw) were recorded in a dual chamber
plethysmograph for 1 h and 3-5 h after challenge of allergic conscious squirrel
monkeys with an aerosol of ascaris antigen. Orally administered CDP-840 (10
mg/kg; 1 h before challenge) produced partial inhibition (41 and 45%,
respectively) of both the acute (1 h post antigen) response and the late (3-5 h
post antigen) response to antigen but failed to alter the response to an aerosol
of leukotriene D4. In a second series of experiments, intravenous CDP-840 (5
mg/kg; 30 min before challenge) showed improved potency, producing 82% inhibition
of the early and 51% inhibition of the late phase response. CDP-840 was inactive
when tested intravenously at 1 mg/kg and was inactive against the 3-5 h response
when administered after the early phase response (5 mg/kg; i.v. 60 min post
antigen challenge). The novel phosphodiesterase IV inhibitor CDP-840 selectively
inhibited antigen-induced bronchoconstriction in conscious squirrel monkeys. This
effect appears to be independent of any direct bronchodilator action. It is
concluded that the activity of CDP-840 in this model may be due to an inhibitory
effect on mediator (e.g., leukotriene) release.
PMID- 9635163
TI - The study of a physiological significance of prolactin in the regulation of
calcium metabolism during pregnancy and lactation in rats.
AB - Since a pharmacological dose of prolactin has previously been reported to enhance
calcium absorption and bone calcium turnover, the role of endogenous prolactin in
the regulation of calcium metabolism was investigated in the balance studies of
Wistar rats between days 17 and 20 of first (P1) and fourth (P4) pregnancy and
between days 12 and 15 of lactation (L). Each group was divided into 3 subgroups:
one subgroup was given 0.9% NaCl (control); one was given 0.3 mg
bromocriptine/100 g body weight ip twice daily for 3 days (to suppress prolactin
secretion); and one was given bromocriptine and 0.25 mg prolactin/100 g body
weight sc daily for 3 days. All three groups received 1 mL/100 g body weight of
1.25 mM calcium gluconate containing 2 mCi (1 Ci = 37 GBq) 45Ca daily for 3 days.
Compared with the two pregnant controls, the L group had higher food consumption
and higher fecal calcium excretion and lower urinary calcium excretion (%
intake). Bromocriptine administration increased total calcium excretion from 59%
intake to 84 and 66% intake in P1 and P4, respectively, suggesting that
endogenous prolactin decreased total calcium excretion. On the other hand,
exogenous prolactin had no effect on the calcium balance of P1 but increased the
total calcium excretion in P4 from 57 to 66% intake. In contrast, the calcium
balance of lactating rats was not altered by suppression of endogenous prolactin
secretion or exogenous prolactin. Considering bone 45Ca content as representing
bone Ca turnover, a lower value of bone 45Ca content indicated an accelerated
bone Ca turnover. It was found that bromocriptine had no effect in P1 but
decreased bone Ca turnover rate in the P4 and L groups, indicating an
accelerating effect of endogenous prolactin on bone Ca turnover in the P4 and L
groups. Exogenous prolactin, on the other hand, decreased bone Ca turnover rate
in every group. Muscle Ca turnover was affected by bromocriptine and exogenous
prolactin in the same manner as bone 45Ca contents. Interestingly, the biphasic
action of prolactin was demonstrated in both calcium absorption and bone calcium
turnover. It could be concluded that during pregnancy and lactation, endogenous
prolactin increases food consumption, fractional calcium absorption, and bone
calcium turnover, apparently to increase calcium availability for fetal
development and milk calcium secretion.
PMID- 9635164
TI - Heparin-releasable lipoprotein lipase activity is increased in cardiomyocytes
after culture.
AB - The activity of lipoprotein lipase (LPL) in adult rat heart cardiomyocytes after
overnight culture on laminin-coated plates for 18-22 h was compared with enzyme
activity in freshly isolated cardiomyocytes. LPL activity in cellular homogenates
from cultured cardiomyocytes and freshly isolated cells was 240 and 233 nmol
oleate released h-1.mg-1 protein, respectively. LPL specific activity (mU/ng LPL
protein) was 0.07 in cultured cells compared with 0.42 in freshly isolated cells,
indicating an increased content of inactive LPL mass after overnight culture. The
heparin-induced release of LPL activity into the medium of cultured
cardiomyocytes (198 nmol.h-1.mg-1) was much greater than heparin-releasable LPL
(HR-LPL) activity (59 nmol.h-1.mg-1) from freshly isolated cells. HR-LPL activity
from cultured cardiomyocytes was dependent on serum (16.3-fold activation) and
was inhibited by high ionic strength (1 M NaCl) and by a polyclonal antibody to
LPL. Cultured cardiomyocytes also had more immunodetectable LPL on the cell
surface compared with freshly isolated cardiomyocytes, consistent with increased
HR-LPL activity. Therefore, overnight culture may permit cardiomyocytes time to
recover from the stress of isolation by increasing the content of LPL on the cell
surface.
PMID- 9635165
TI - Serum leptin levels and energy expenditure in normal weight women.
AB - To investigate whether circulating leptin levels are associated with energy
expenditure in healthy humans, doubly labeled water energy measurements and food
intake assessment were carried out in 27 women (mean age, 48.6 years; weight,
61.9 kg; body mass index, 23.2). Energy expenditure was determined over 13 days.
Food intake was measured by 7-day food records. Leptin was measured by
radioimmunoassay. Leptin level was strongly associated with percentage body fat
(r = 0.59; p < 0.001), fat mass (r = 0.60; p < 0.001), and body mass index (r =
0.41; p = 0.03), but no correlation was observed with energy expenditure (r =
0.02; p = 0.93). After controlling for percentage body fat, a positive
association of leptin level with energy expenditure of marginal significance (p =
0.06) was observed. There were no significant univariate associations of age,
physical activity, lean body mass, height, or dietary variables with leptin
level. When controlling for body fat, a significant positive correlation was
observed for percent energy from carbohydrate and negative correlations with
dietary fat and alcohol intake. These findings confirm previous associations
between leptin and body fat content and suggest a relationship between serum
leptin and energy expenditure level in healthy humans.
PMID- 9635166
TI - Microbial resistance to antimicrobial drugs.
PMID- 9635167
TI - Questioning some of the CVMA pet food recommendations.
PMID- 9635168
TI - ELISA testing for antibody to Mycobacterium paratuberculosis.
PMID- 9635169
TI - An ethicist's commentary on the case of the cat who fractures both legs after a
declaw.
PMID- 9635170
TI - End tidal halothane concentration and postoperative analgesia requirements in
dogs: a comparison between intravenous oxymorphone and epidural bupivacaine alone
and in combination with oxymorphone.
AB - The purpose of this study was to compare the effects of epidural bupivacaine
(BUP) and oxymorphone/bupivacaine (O/B) and intravenous (i.v.) oxymorphone (IVO)
on halothane requirements during hind end surgery and postoperative analgesia in
24 dogs. Dogs were randomly assigned to treatment groups: O/B--oxymorphone (0.1
mg/kg) in 0.75% bupivacaine (1 mg/kg for a total volume of 0.2 ml/kg); BUP--0.5%
bupivacaine (1 mg/kg for a total volume of 0.2 ml/kg) with i.v. oxymorphone (0.05
mg/kg) postoperatively; and IVO--oxymorphone (0.05 mg/kg) pre- and
postoperatively. Heart rate (HR), respiratory rate, arterial blood pressure, end
tidal carbon dioxide and halothane, and arterial blood gases were recorded prior
to treatment and every 15 minutes thereafter. Once surgery had begun, end-tidal
halothane concentrations were decreased as low as possible while still
maintaining a stable anesthetic plane. Data were analyzed using ANOVA with P <
0.05 considered significant. End-tidal halothane requirements did not differ
significantly among treatments. Respiratory depression was increased and HR was
decreased in the O/B and IVO groups. Postoperative analgesic requirements were
significantly less in dogs receiving O/B.
PMID- 9635171
TI - External skeletal fixation for treatment of comminuted fractures in wapiti: 5
cases.
AB - External skeletal fixators were used successfully to treat severely comminuted
fractures in 5 wapiti.
PMID- 9635172
TI - Cholecystadenocarcinoma in a cat.
AB - A malignant neoplastic process originating from gall bladder epithelium was
diagnosed in a 14-year-old, spayed female, domestic shorthair cat. The tumor
produced widespread pulmonary and lymphatic metastases. The clinical and
pathological manifestations are described. Neoplasia arising from the gall
bladder epithelium is rarely reported in animals.
PMID- 9635173
TI - Intestinal obstruction by stones in a turtle.
PMID- 9635174
TI - Streptococcus acidominimus in a case of bovine fibrinopurulent metritis.
PMID- 9635175
TI - Bacterial resistance.
PMID- 9635177
TI - A clear view.
PMID- 9635178
TI - Illusions as neuro-signs.
PMID- 9635179
TI - A bacterial antibiotic resistance gene with eukaryotic origins.
PMID- 9635180
TI - Nucleocytoplasmic transport: driving and directing transport.
AB - Nucleocytoplasmic transport involves assembly and movement across the nuclear
envelope of cargo-receptor complexes that interact with the small GTPase Ran. The
asymmetric distribution of Ran regulator proteins, RanGAP1 and RCC1, provides the
driving force and directionality for nuclear transport.
PMID- 9635181
TI - Chromatin transcription: clearing the gridlock.
AB - A factor has been purified that specifically facilitates RNA chain elongation in
a chromatin context; the properties of this factor help to define the challenges
that lie ahead in understanding how RNA polymerase manages to transcribe DNA that
is packaged into chromatin.
PMID- 9635182
TI - Neurophysiology: sensing and categorizing.
AB - Objects differ along many stimulus dimensions, but observers typically group them
into fewer 'categories' according to their potential use or behavioral relevance.
New experiments in awake, behaving monkeys open a window onto the process of
stimulus categorization within the central nervous system.
PMID- 9635183
TI - Biodiversity conservation: does phylogeny matter?
AB - To conserve biodiversity, it is necessary not only to maximize the number of taxa
that are saved today, but also to guarantee the maintenance of high levels of
biological diversity in the future. A recent analysis argues that, to achieve
this, consideration of phylogeny is essential.
PMID- 9635184
TI - Chromosome movement: kinetochores motor along.
AB - The equal division of chromosomes among daughter cells at mitosis involves a
complex series of kinetochore-dependent chromosome movements. The kinetochore
associated CENP-E motor protein is critical for the sustained movement of
chromosomes towards the metaphase plate during chromosome congression.
PMID- 9635185
TI - Integrins: a role for adhesion molecules in olfactory memory.
AB - A gene required for short-term memory in Drosophila, Volado, encodes an alpha
integrin and is preferentially expressed in the mushroom bodies of the adult
brain. Adhesion molecules of this kind may play a role in olfactory memory by
altering the strength of synaptic connections in an experience-dependent manner.
PMID- 9635186
TI - Membrane fusion: all done with SNAREpins?
AB - SNARE proteins are sufficient to fuse artificial membranes together. In the cell,
vesicle transport may rely on fusion mediated by interaction between vesicle (v)
and target (t) SNAREs, whereas the homotypic fusion of organelle biogenesis may
be mediated by t-SNARE-t-SNARE interaction.
PMID- 9635187
TI - Intracellular motility: how can we all work together?
AB - Recent results reinforce the view that actin-based and microtubule-based motility
systems do not operate independently, but are used in coordinated fashion to
determine intracellular localization of cargo such as organelles.
PMID- 9635188
TI - Rng2p, a protein required for cytokinesis in fission yeast, is a component of the
actomyosin ring and the spindle pole body.
AB - BACKGROUND: An actomyosin-based contractile ring plays a pivotal role in
cytokinesis. Despite the identification of many components of the ring, the steps
involved in its assembly are unknown. The fission yeast Schizosaccharomyces pombe
is an attractive organism in which to study cytokinesis because its cell cycle
has been well characterized; it divides by medial fission using an actomyosin
ring; and a number of S. pombe mutants defective in actomyosin ring assembly have
been isolated. Here, we have characterized one such mutant, rng2. RESULTS:
Temperature-sensitive rng2 mutants accumulated F-actin cables in the medial
region of the cell but failed to organize the cables into a ring. In rng2-null
mutants, only a spot-like structure containing F-actin was detected. The rng2+
gene encodes a protein related to human IQGAP1, a protein that binds actin and
calmodulin and is a potential effector for the Rho family of GTPases. Rng2p
localized to the actomyosin ring and to the spindle pole body (SPB) of interphase
and mitotic cells. Localization of Rng2p to the actomyosin ring but not the SPB
required F-actin. Rng2p interacted with calmodulin, a component of the SPB and
the actomyosin ring. The rng2 gene showed genetic interactions with three other
actomyosin ring assembly mutants, cdc4, cdc12, and rng5. CONCLUSIONS: The S.
pombe IQGAP-related protein Rng2p is a component of the actomyosin ring and the
SPB and is required for actomyosin ring construction following assembly of F
actin at the division site.
PMID- 9635189
TI - Roles of Armadillo, a Drosophila catenin, during central nervous system
development.
AB - BACKGROUND: Neural development requires that neurons communicate and co-operate
with one another and with other cell types in their environment. Drosophila
Armadillo and its vertebrate homolog beta-catenin have dual roles in epithelial
cells: transducing signals from the Wingless/Wnt family of proteins and working
with cadherins to mediate cell adhesion. Wingless/Wnt signaling also directs
certain cell fates in the central nervous system (CNS), and cadherins and
catenins are thought to function together during neural development. RESULTS: We
identified and analyzed the biochemical properties of a second armadillo isoform,
with a truncated carboxyl terminus generated by alternative splicing. This
isoform was found to accumulate in differentiating neurons. Using armadillo
alleles that selectively inactivate the cell adhesion or the Wingless signaling
functions of Armadillo, we found that Armadillo had two sequential roles in
neural development. Armadillo function in Wingless signal transduction was
required early in development for determination of neuroblast fate. Later in
development, disruption of the cell-cell adhesion function of Armadillo resulted
in subtle defects in the construction of the axonal scaffold. Mutations in the
gene encoding the Drosophila tyrosine kinase Abelson substantially enhanced the
severity of the CNS phenotype of armadillo mutations, consistent with these
proteins functioning co-operatively at adherens junctions in both the CNS and the
epidermis. CONCLUSIONS: This is one of the first demonstrations of a role for the
cadherin-catenin system in the normal development of the CNS. The genetic
interactions between armadillo and abelson point to a possible role for the
tyrosine kinase Abelson in cell-cell adhesive junctions in both the CNS and the
epidermis.
PMID- 9635190
TI - Cut1 is loaded onto the spindle by binding to Cut2 and promotes anaphase spindle
movement upon Cut2 proteolysis.
AB - BACKGROUND: The Cut1 and Cut2 proteins of the fission yeast Schizosaccharomyces
pombe form a complex and are required for the separation of sister chromatids
during anaphase. Polyubiquitinated Cut2 degrades at the onset of anaphase and
this degradation, like that of mitotic cyclin, is dependent on the anaphase
promoting complex/cyclosome. Expression of Cut2 that cannot be degraded blocks
sister chromatid separation and anaphase spindle elongation. Here, we have
investigated the role of the Cut1-Cut2 interaction in sister chromatid
separation. RESULTS: The carboxyl terminus of Cut2 interacts with the amino
terminus of Cut1, and temperature-sensitive Cut2 mutants expressed Cut2 proteins
that contain substitutions in the carboxyl terminus and fail to interact with
Cut1, resulting in aberrant anaphase. Localization of Cut1 alters dramatically
during the cell cycle. Cut1 is retained in the cytoplasm during interphase and
moves to the mitotic spindle pole bodies and the spindle upon entry into
prophase, when spindles are formed. The association between Cut2 and Cut1 is
needed for the localization of Cut1 to the spindles, as Cut1 remains unbound to
the spindle if complex formation is impaired. Cut2 degrades during anaphase, but
Cut1 remains bound to the anaphase spindle. This association with the anaphase
spindle requires the conserved carboxyl terminus of Cut1. CONCLUSIONS: Complex
formation between Cut1 and Cut2 is needed for the onset of normal anaphase. Cut2
is required for loading Cut1 onto the spindle at prophase and Cut2 proteolysis is
needed for the active participation of Cut1 in sister chromatid separation.
PMID- 9635191
TI - The importance of timing differentiation during limb muscle development.
AB - BACKGROUND: Skeletal muscle of trunk, limbs and tongue develops from a small
population of cells that originates from somites. Although promoters and
inhibitors of muscle differentiation have been isolated, nothing is known about
how the amplification of the muscle precursor pool is regulated; this
amplification provides muscle mass during development. Furthermore, little is
known about how cells accumulate in the pre-muscle masses in the limbs. We
investigated the role of bone morphogenetic protein (BMPs) and Sonic hedgehog
(Shh) during proliferation, differentiation and positioning of muscle. RESULTS:
The proliferation of muscle precursors in limbs was linked to Pax-3 expression.
Ectoderm removal downregulated Pax-3 expression, arrested proliferation and
prematurely initiated muscle differentiation which exhausted the muscle precursor
pool and prevented further muscle growth. BMP-2, BMP-4 and BMP-7 had a dose
dependent effect on pre-myogenic cells: low concentrations maintained a Pax-3
expressing proliferative population, substituting for ectoderm-derived
proliferative signals and delaying differentiation, whereas high concentrations
prevented muscle development, probably by inducing apoptosis. In the limb, Shh
upregulated Bmp-2 and Bmp-7 expression which delayed muscle differentiation,
upregulated Pax-3, amplified the muscle precursor population and stimulated
excessive muscle growth. CONCLUSIONS: These data indicate that embryonic muscle
growth requires muscle differentiation to be delayed. Muscle differentiation may
occur through a default pathway after cells escape proliferative signals.
Positioning of muscle is regulated by high concentrations of BMPs, thus a single
type of signalling molecule can determine crucial steps in muscle development:
when and where to proliferate, and when and where to differentiate.
PMID- 9635192
TI - Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres.
AB - The mammalian Ku70 and Ku86 proteins form a heterodimer that binds to the ends of
double-stranded DNA in vitro and is required for repair of radiation-induced
strand breaks and V(D)J recombination [1,2]. Deletion of the Saccharomyces
cerevisiae genes HDF1 and HDF2--encoding yKu70p and yKu80p, respectively-
enhances radiation sensitivity in a rad52 background [3,4]. In addition to repair
defects, the length of the TG-rich repeat on yeast telomere ends shortens
dramatically [5,6]. We have shown previously that in yeast interphase nuclei,
telomeres are clustered in a limited number of foci near the nuclear periphery
[7], but the elements that mediate this localization remained unknown. We report
here that deletion of the genes encoding yKu70p or its partner yKu80p altered the
positioning of telomeric DNA in the yeast nucleus. These are the first mutants
shown to affect the subnuclear localization of telomeres. Strains deficient for
either yKu70p or yKu80p lost telomeric silencing, although they maintained
repression at the silent mating-type loci. In addition, the telomere-associated
silencing factors Sir3p and Sir4p and the TG-repeat-binding protein Rap1p lost
their punctate pattern of staining and became dispersed throughout the
nucleoplasm. Our results implicate the yeast Ku proteins directly in aspects of
telomere organization, which in turn affects the repression of telomere-proximal
genes.
PMID- 9635193
TI - Telomere maintenance is dependent on activities required for end repair of double
strand breaks.
AB - Telomeres are functionally distinct from ends generated by chromosome breakage,
in that telomeres, unlike double-strand breaks, are insulated from recombination
with other chromosomal termini [1]. We report that the Ku heterodimer and the
Rad50/Mre11/Xrs2 complex, both of which are required for repair of double-strand
breaks [2-5], have separate roles in normal telomere maintenance in yeast. Using
epistasis analysis, we show that the Ku end-binding complex defined a third
telomere-associated activity, required in parallel with telomerase [6] and Cdc13,
a protein binding the single-strand portion of telomere DNA [7,8]. Furthermore,
loss of Ku function altered the expression of telomere-located genes, indicative
of a disruption of telomeric chromatin. These data suggest that the Ku complex
and the Cdc13 protein function as terminus-binding factors, contributing distinct
roles in chromosome end protection. In contrast, MRE11 and RAD50 were required
for the telomerase-mediated pathway, rather than for telomeric end protection; we
propose that this complex functions to prepare DNA ends for telomerase to
replicate. These results suggest that as a part of normal telomere maintenance,
telomeres are identified as double-strand breaks, with additional mechanisms
required to prevent telomere recombination. Ku, Cdc13 and telomerase define three
epistasis groups required in parallel for telomere maintenance.
PMID- 9635194
TI - Dissecting the role of N-myc in development using a single targeting vector to
generate a series of alleles.
AB - The N-myc proto-oncogene is expressed in many organs of the mouse embryo,
suggesting that it has multiple functions. A null mutation leads to mid-gestation
lethality [1-4], obscuring the later roles of the gene in organogenesis. We have
generated a multi-purpose gene alteration by combining the potential for
homologous and site-specific recombination in a single targeting vector, and
using the selectable marker for neomycin-resistance, neo, to downregulate gene
activity. This allowed us to create a series of alleles that led to different
levels of N-myc expression. The phenotypes revealed a spectrum of developmental
problems. The hypomorphic allele produced can be repaired in situ by Cre
recombinase-mediated DNA excision. We show here for the first time the use of a
single targeting vector to generate an allelic series. This, and the possibility
of subsequent lineage-specific or conditional allele repair in situ, represent
new genome modification strategies that can be used to investigate multiple
functions of a single gene.
PMID- 9635195
TI - Fate mapping of the mouse midbrain-hindbrain constriction using a site-specific
recombination system.
AB - The mouse midbrain-hindbrain constriction is centrally involved in patterning of
the midbrain and anterior hindbrain (cerebellum), as revealed by recent genetic
studies using mice and embryological studies in chick (reviewed in [1,2]). This
region can act as an organizer region to induce midbrain and cerebellar
development. Genes such as Engrailed-1, Pax-2 and Pax-5, which are expressed in
the embryonic cells that will form the midbrain and the cerebellum, are required
for development of these regions. Fate-mapping experiments at early somite stages
in chick have revealed that the cerebellar primordium is located both anterior
and posterior to the midbrain-hindbrain constriction, whereas midbrain precursors
lie more anteriorly. Fate mapping in mice has been complicated by the
inaccessibility of the postimplantation embryo. Here, we report the use of a new
in vivo approach involving the Cre-IoxP site-specific recombination system [3] to
map the fate of cells in the mouse midbrain-hindbrain constriction. We show that
cells originating in the mouse dorsal midbrain-hindbrain constriction during
embryonic days 9-12 contribute significantly to the medial cerebellum and
colliculi. Our data demonstrate the feasibility of using a recombinase-based
lineage-tracing system for fate mapping in the mouse.
PMID- 9635196
TI - Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role
for IL-13 in the regulation of Th2 responses.
AB - Allergens and infections with parasitic helminths preferentially induced Th2
immune responses associated with elevated levels of serum immunoglobulin E (IgE)
and expansion of eosinophils and mast cells. Interleukin-4 (IL-4) is a key
cytokine in the differentiation of naive CD4+ T cells into Th2 cells, which
produce a panel of cytokines including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13
[1] and have been shown to trigger recovery from gastrointestinal nematodes [2].
Nonetheless, mice deficient for IL-4 have been shown to develop residual Th2
responses [3-5] and can expel the nematode Nippostrongylus brasiliensis [6],
suggesting that there is a functional equivalent of IL-4 in these processes. IL
13 is a cytokine that shares some, but not all, biological activities with IL-4
[7,8]. There is now compelling evidence that IL-4 and IL-13 share receptor
components, including IL-4R alpha and IL-13R alpha 1 [9]. In order to dissect the
roles of IL-4 and IL-13 in the regulation of Th2 cells and in the response to
nematode infections, we looked for differences between mice deficient for either
the IL-4 gene or the IL-4R alpha gene. Unlike IL-4, IL-4R alpha was required for
control of N. brasiliensis, and Th2 development during infection--as
characterized by cytokine production, GATA-3 and surface CD30 expression--was
more severely affected in IL-4R alpha-/- mice than in IL-4-/- mice. Injection of
recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2-/- mice.
Our results suggest that IL-13 regulates Th2 responses to nematode infection and
requires IL-4R alpha.
PMID- 9635197
TI - Two phases of Hox gene regulation during early Xenopus development.
AB - We have shown previously that fibroblast growth factor (FGF) signalling in
posterior regions of the Xenopus embryo is required for the development of the
trunk and tail via a molecular pathway that includes the caudal-related gene
Xcad3 and the posterior Hox genes [1]. These results have been contested by the
work of Kroll and Amaya [2], which shows that Xenopus embryos transgenic for a
dominant-negative form of the FGF receptor (FGF-RI) express posterior Hox genes
normally, leading these authors to suggest that the FGFs are not required for
anteroposterior (A-P) patterning of the dorsal axis. In order to investigate the
apparent discrepancy between these studies, we have produced Xenopus embryos
transgenic for two inhibitors of the FGF/Caudal pathway: a kinase-deficient
dominant-negative FGF receptor (XFD) [3]; and a domain-swapped form of Xcad3
(Xcad-EnR) in which the activation domain of Xcad3 is replaced by the repression
domain of the Drosophila Engrailed protein. Both of these were introduced as
fusions with the green fluorescent protein (GFP), which allows identification of
non-mosaic transgenic embryos at early gastrula stages by simply looking for GFP
fluorescence. Analysis of gene expression in embryos transgenic for these
constructs indicated that the activation of posterior Hox genes during early
neurula stages absolutely requires FGF signalling and transcriptional activation
by Xcad3, while the maintenance of Hox gene expression in the trunk and tail
during later development is independent of both FGF and Xcad.
PMID- 9635198
TI - Cognitive neuroscience.
PMID- 9635199
TI - Beyond images.
PMID- 9635200
TI - Beyond the single study: function/location metanalysis in cognitive neuroimaging.
AB - Cognitive neuroimaging maps the brain locations of mental operations. This
process is iterative, as no single study can fully characterize a mental
operation or its brain location. This iterative discovery process, in combination
with the location-reporting standard (i.e. spatial coordinates) of the cognitive
neuroimaging community, has engendered a new form of metanalysis. Response
locations from multiple studies have been analyzed collectively so as to better
describe the spatial distribution of brain activations, with promising results.
New hypotheses regarding elementary mental operations and their respective brain
locations are being generated and refined via metanalysis. These hypotheses are
being tested and confirmed by subsequent, prospective experiments.
Function/location metanalysis is an important new tool for hypothesis generation
in cognitive neuroimaging. This form of metanalysis is fundamentally different
from the effect-size metanalyses prevalent in other literatures, with unique
advantages and challenges.
PMID- 9635201
TI - Brain mapping in animals and humans.
AB - Studies using functional magnetic resonance imaging (fMRI) to map cortical areas
in humans have revealed many similarities with recent cortical mapping studies
from nonhuman primates as well as some striking differences. Improved methods for
analyzing, displaying and averaging fMRI data on an unfolded cortical surface
atlas are poised to improve the integration of information across burgeoning
numbers of imaging studies. By combining fMRI with electrical and passive
magnetic imaging modalities, the millisecond-to-millisecond sequence of
activation of different cortical regions elicited by an event can be imaged,
provided the regions are sufficiently far apart.
PMID- 9635202
TI - Spatial maps for the control of movement.
AB - Neurons in the ventral premotor cortex of the monkey encode the locations of
visual, tactile, auditory and remembered stimuli. Some of these neurons encode
the locations of stimuli with respect to the arm, and may be useful for guiding
movements of the arm. Others encode the locations of stimuli with respect to the
head, and may be useful for guiding movements of the head. We suggest that a
general principle of sensory-motor integration is that the space surrounding the
body is represented in body-part-centered coordinates. That is, there are
multiple coordinate systems used to guide movement, each one attached to a
different part of the body. This and other recent evidence from both monkeys and
humans suggest that the formation of spatial maps in the brain and the guidance
of limb and body movements do not proceed in separate stages but are closely
integrated in both the parietal and frontal lobes.
PMID- 9635203
TI - Temporal dynamics of early perceptual processing.
AB - Recordings of electrical and magnetic brain responses to sensory stimulation
provide high-resolution measures of the time course of early perceptual
processing. Spatio-temporal analyses of brain activity patterns during the first
200 ms after stimulus presentation have characterized the timing of attentional
selection processes and different stages of feature encoding and pattern
analyses. Recent studies that incorporate blood flow neuroimaging techniques
provide support for mechanisms of early selection of attended visual inputs in
extrastriate cortical pathways. The spatial tuning properties of early auditory
selection have also been delineated. Electrical and magnetic responses that index
the encoding of higher-order pattern information have been identified in both
visual and auditory modalities and localized to specific cortical areas.
PMID- 9635204
TI - Neural correlates of visual and motor decision processes.
AB - Recent research has clarified and revealed characteristics of perceptual and
motor decision processes in the brain. A democracy of sensory neurons
discriminate the properties of a stimulus, while competition contrasts the
attributes of stimuli across the visual field to locate conspicuous stimuli.
Salience and significance are weighed to select an object on which to focus
attention and action. Experimentally combining neural and mental chronometry has
determined the contribution of perceptual and motor processes to the duration and
variability of behavioral reaction time. Whereas perceptual processing occupies a
relatively constant amount of time for a given stimulus condition, the processes
of mapping particular stimuli onto the appropriate behavior and preparing the
motor response provide flexibility but introduce delay and variability in
reaction time.
PMID- 9635205
TI - Perceiving visually presented objects: recognition, awareness, and modularity.
AB - Object perception may involve seeing, recognition, preparation of actions, and
emotional responses--functions that human brain imaging and neuropsychology
suggest are localized separately. Perhaps because of this specialization, object
perception is remarkably rapid and efficient. Representations of componential
structure and interpolation from view-dependent images both play a part in object
recognition. Unattended objects may be implicitly registered, but recent
experiments suggest that attention is required to bind features, to represent
three-dimensional structure, and to mediate awareness.
PMID- 9635206
TI - Properties and mechanisms of perceptual priming.
AB - Recent evidence suggests that the behavioral phenomenon of perceptual priming and
the physiological finding of decreased neural responses with item repetition have
similar properties. Both the behavioral and neurophysiological effects show
graded changes with multiple repetition, are resistant to manipulations of
particular stimulus attributes (e.g. size and location), and occur independently
of awareness. These and other recent findings (e.g. from functional brain imaging
in humans) suggest that perceptual priming may be mediated by decreased neural
responses associated with perceptual learning.
PMID- 9635207
TI - Recent developments in working memory.
AB - Research on the visual and verbal subsystems of working memory has shown vigorous
development, with PET, fMRI and behavioral data all supporting separate systems,
with further fractionation being likely. Analysis of executive processes is
revealing a range of subprocesses, providing a very fruitful field for the
interaction of cognitive psychology, neuropsychology and functional imaging.
PMID- 9635208
TI - To dream or not to dream? Relevant data from new neuroimaging and
electrophysiological studies.
AB - The study of sleep and dreams has enjoyed a major breakthrough with recent
findings from brain imaging studies in humans. Several independent groups have
shown global deactivation of the brain during non rapid eye movement sleep and a
regionally selective reactivation during rapid eye movement sleep. These results
are complemented by new brain lesion and electrophysiological recording data to
give a detailed picture of the brain dynamics of changes in conscious state.
PMID- 9635209
TI - Crossmodal attention.
AB - Most selective attention research has considered only a single sensory modality
at a time, but in the real world, our attention must be coordinated crossmodally.
Recent studies reveal extensive crossmodal links in attention across the various
modalities (i.e. audition, vision, touch and proprioception). Attention typically
shifts to a common location across the modalities, despite the vast differences
in their initial coding of space. These spatial synergies in attention can be
maintained even when receptors are realigned across the modalities by changes in
posture. Some crossmodal integration can arise preattentively. The mechanisms
underlying these crossmodal links can be examined in a convergent manner by
integrating behavioural studies of normal subjects and brain-damaged patients
with neuroimaging and neurophysiological studies.
PMID- 9635210
TI - Neural organization and plasticity of language.
AB - Powerful advances in neuroimaging techniques have added to and refined classical
descriptions of the neurobiology of language in adults. Recent studies have
employed these methodologies to study the nature and extent of plasticity of
language-relevant aspects of cerebral organization in adults, in early and late
bilinguals and in people who have acquired language through different modalities.
Studies of children have documented dynamic shifts in cerebral organization over
the course of language acquisition. Each of these different approaches has
revealed constraints on the identity of the neural systems that mediate language;
these studies have also described the marked and specific effects of language
experience on the organization of these systems.
PMID- 9635211
TI - Images of psychopathology.
AB - Brain imaging continues to provide important data about brain structure,
neurotransmitter function and the physiological basis of cognitive processes, as
these relate to schizophrenia and mood disorders. A unifying theoretical
perspective, however, that can clarify the precise nature of the biological basis
of these diverse psychiatric conditions is lacking. It is becoming increasingly
evident that a lesion model is inappropriate and that a more relevant
characterisation will be found in terms of disorders of functional
interconnections between brain regions.
PMID- 9635212
TI - Cognitive neuroscience of attention deficit hyperactivity disorder and
hyperkinetic disorder.
AB - Currently, diagnoses of attention deficit hyperactivity disorder (ADHD) and
hyperkinetic disorder (HKD) are made on the basis of phenomenology, but
information is accumulating from the neurosciences about the biological bases of
these disorders. Recent studies addressing the neuropsychology, neuroanatomy,
neurochemistry, and molecular biology of ADHD/HKD document abnormalities in well
defined neuroanatomical networks and neurochemical pathways. Magnetic resonance
imaging (MRI) studies have shown that some regions of the frontal lobes (anterior
superior and inferior) and basal ganglia (caudate nucleus and globus pallidus)
are about 10% smaller in ADHD groups than in control groups of children, and
molecular genetic studies have shown that diagnosis of ADHD is associated with
polymorphisms in some dopamine genes (the dopamine D4 receptor gene and the
dopamine transporter gene).
PMID- 9635213
TI - Genetically modified mice and cognition.
AB - Cognition in transgenic and knockout mice is preferentially assessed by spatial
learning in the Morris water maze. Awareness is growing, however, that the
putative cognitive deficits observed using such a paradigm may be biased by the
genetic background and behavioral peculiarities of the specific animals used.
Recent progress in cognitive research includes new behavioral tests and refined
analysis of performance impairments. Advances in our understanding of memory and
learning are being made possible through use of transgenic rescue of disrupted
genes, inducible and reversible gene targeting in selected brain regions, and
single-cell recordings of hippocampal place cells in mutant mice.
PMID- 9635214
TI - Recovery of cognitive functions following nonprogressive brain injury.
AB - It has recently become clear that the adult human brain is capable of more
plasticity than previously thought. Investigations into the natural history of
change following brain injury demonstrate that partial recovery of function can
and does occur. Furthermore, there is increasing evidence that intervention
through re-training or provision of compensatory memory aids can result in
improved cognitive functioning.
PMID- 9635215
TI - What is cognitive behavioural therapy and does it work?
PMID- 9635216
TI - The hippocampus, consolidation and on-line memory.
PMID- 9635217
TI - Consolidation and the hippocampal complex revisited: in defense of the multiple
trace model.
PMID- 9635218
TI - Contextualism and developmental psychopathology.
PMID- 9635219
TI - Social context in developmental psychopathology: recommendations for future
research from the MacArthur Network on Psychopathology and Development. The
MacArthur Foundation Research Network on Psychopathology and Development.
AB - Accumulating evidence suggests that social contexts in early life have important
and complex effects on childhood psychopathology. Spurred by the lack of an
explicit operational definition that could guide the study of such effects, we
define a social context operationally as "a set of interpersonal conditions,
relevant to a particular behavior or disorder and external to, but shaped and
interpreted by, the individual child." Building on this definition, we offer a
series of recommendations for future research, based on five theoretically
derived propositions: (a) Contexts are nested and multidimensional; (b) contexts
broaden, differentiate, and deepen with age, becoming more specific in their
effects; (c) contexts and children are mutually determining; (d) a context's
meaning to the child determines its effects on the child and arises from the
context's ability to provide for fundamental needs; and (e) contexts should be
selected for assessment in light of specific questions or outcomes. As reflected
in an increasingly rich legacy of literature on child development and
psychopathology, social contexts appear to influence emerging mental disorders
through dynamic, bidirectional interactions with individual children. Future
research will benefit from examining not only statistical interactions between
child- and context-specific factors, but also the actual transactions between
children and contexts and the transduction of contextual influences into pathways
of biological mediation. Because adverse contexts exert powerful effects on the
mental health of children, it is important for the field to generate new, more
theoretically grounded research addressing the contextual determinants of
psychological well-being and disorder.
PMID- 9635220
TI - The effect of the level of aggression in the first grade classroom on the course
and malleability of aggressive behavior into middle school.
AB - This paper is on the influences of the classroom context on the course and
malleability of aggressive behavior from entrance into first grade through the
transition into middle school. Nineteen public elementary schools participated in
developmental epidemiologically based preventive trials in first and second
grades, one of which was directed at reducing aggressive, disruptive behavior. At
the start of first grade, schools and teachers were randomly assigned to
intervention or control conditions. Children within each school were assigned
sequentially to classrooms from alphabetized lists, followed by checking to
insure balanced assignment based on kindergarten behavior. Despite these
procedures, by the end of first quarter, classrooms within schools differed
markedly in levels of aggressive behavior. Children were followed through sixth
grade, where their aggressive behavior was rated by middle school teachers.
Strong interactive effects were found on the risk of being highly aggressive in
middle school between the level of aggressive behavior in the first grade
classrooms and each boy's own level of aggressive, disruptive behavior in first
grade. The more aggressive first grade boys who were in higher aggressive first
grade classrooms were at markedly increased risk, compared both to the median
first grade boys, and compared to aggressive males in lower aggressive first
grade classrooms. Boys were already behaving more aggressively than girls in
first grade; and no similar classroom aggression effect was found among girls,
although girls' own aggressive behavior did place them at increased risk. The
preventive intervention effect, already reported elsewhere to reduce aggressive
behavior among the more aggressive males, appeared to do so by reducing high
levels of classroom aggression. First grade males' own poverty level was
associated with higher risk of being more aggressive, disruptive in first grade,
and thereby increased their vulnerability to classroom level of aggression. Both
boys and girls in schools in poor communities were at increased risk of being
highly aggressive in middle school regardless of their levels of aggressive
behavior in first grade. These results are discussed in terms of life
course/social field theory as applied to the role of contextual influences on the
development and etiology of severe aggressive behavior.
PMID- 9635221
TI - Resolving conflict creatively: evaluating the developmental effects of a school
based violence prevention program in neighborhood and classroom context.
AB - This study evaluated the short-term impact of a school-based violence prevention
initiative on developmental processes thought to place children at risk for
future aggression and violence and examined the influence of classroom and
neighborhood contexts on the effectiveness of the violence prevention initiative.
Two waves of developmental data (fall and spring) were analyzed from the 1st year
of the evaluation of the Resolving Conflict Creatively Program (RCCP), which
includes 5053 children from grades two to six from 11 elementary schools in New
York City. Three distinct profiles of exposure to the intervention were derived
from Management Information System (MIS) data on between classroom differences in
teacher Training and Coaching in RCCP, Classroom Instruction in RCCP, and
percentages of students who are Peer Mediators. Developmental processes that
place children at risk were found to increase over the course of the school year.
Children whose teachers had a moderate amount of training and coaching from RCCP
and who taught many lessons showed significantly slower growth in aggression
related processes, and less of a decrease in competence-related processes,
compared to children whose teachers taught few or no lessons. Contrary to
expectation, children whose teachers had a higher level of training and coaching
in the RCCP but taught few lessons showed significantly faster growth over time
in aggressive cognitions and behaviors. The impact of the intervention on
children's social cognitions (but not on their interpersonal behaviors) varied by
context. Specifically the positive effect of High Lessons was dampened for
children in high-risk classrooms and neighborhoods. Implications for future
research on developmental psychopathology in context and for the design of
preventive interventions are discussed.
PMID- 9635222
TI - Impoverishment and child maltreatment in African American and European American
neighborhoods.
AB - Although it is well documented that child maltreatment exerts a deleterious
impact on child adaptation, much less is known about the precise etiological
pathways that eventuate in child abuse and neglect. This paper reports on a
multimethod ecological study of the relationship between neighborhood structural
factors and child maltreatment reports in African American and European American
census tracts. The study had two major components. First, in an aggregate
analysis, the effects of four measures of community structure (impoverishment,
child care burden, instability, and geographic isolation) on child maltreatment
report rates were examined separately for predominantly African American (n = 94)
and predominantly European American (n = 189) census tracts. Impoverishment in
particular had a significantly weaker effect on maltreatment rates in African
American than in European American neighborhoods. Second, focused ethnographies
were conducted in four selected census tracts with child maltreatment report
rates in the highest and lowest quartiles. Ethnographic data point to the
importance of the social fabric in accounting for differences in child
maltreatment report rates by predominant neighborhood ethnicity.
PMID- 9635223
TI - An ecological-transactional analysis of children and contexts: the longitudinal
interplay among child maltreatment, community violence, and children's
symptomatology.
AB - Cicchetti and Lynch have conceptualized ecological contexts as consisting of
nested levels with varying degrees of proximity to the individual. These levels
of the environment interact and transact with each other over time in shaping
individual development and adaptation. With a sample of maltreated (n = 188) and
nonmaltreated (n = 134) children between the ages of 7 and 12 years, this
investigation employed a 1-year longitudinal design to conduct an ecological
transactional analysis of the mutual relationships among community violence,
child maltreatment, and children's functioning over time. Indicators of
children's functioning were externalizing and internalizing behavior problems and
self-rated traumatic stress reactions, depressive symptomatology, and self
esteem. Either full or partial support was obtained for the study's primary
hypotheses. Rates of maltreatment, particularly physical abuse, were related to
levels of child-reported violence in the community. In addition, child
maltreatment and exposure to community violence were related to different aspects
of children's functioning. Specific effects were observed for neglect and sexual
abuse and for witnessing and being victimized by violence in the community.
Finally, there was evidence that children and their contexts mutually influence
each other over time. Results were discussed within the framework of an
ecological-transactional model of development.
PMID- 9635224
TI - Structural and experiential neighborhood contexts, developmental stage, and
antisocial behavior among urban adolescents in poverty.
AB - This study explored the effects of structural and experiential neighborhood
factors and developmental stage on antisocial behavior, among a sample of poor
urban adolescents in New York City. Conceptually and empirically distinct
profiles of neighborhood experience were derived from the data, based on measures
of perceived neighborhood cohesion, poverty-related hassles, and involvement in
neighborhood organizations and activities. Both the profiles of neighborhood
experience and a measure of census-tract-level neighborhood hazard (poverty and
violence) showed relationships to antisocial behavior. Contrary to expectation,
higher levels of antisocial behavior were reported among adolescents residing in
moderate-structural-risk neighborhoods than those in high-structural-risk
neighborhoods. This effect held only for teens in middle (not early) adolescence
and was stronger for teens perceiving their neighborhoods as hassling than for
those who did not. Implications for future research and preventive intervention
are discussed.
PMID- 9635225
TI - Maternal depressive disorder and contextual risk: contributions to the
development of attachment insecurity and behavior problems in toddlerhood.
AB - Research has shown that offspring of depressed caregivers are at increased risk
for maladaptive development and emotional difficulties. Specifically, infants and
toddlers of depressed mothers have been shown to evidence higher percentages of
insecure attachments and more behavioral difficulties than offspring of
nondisordered mothers. However, even in studies that reveal significant
differences between children of depressed and nondepressed caregivers, a
substantial number of children with depressed caregivers do not evidence
dysfunction. Such findings have resulted in increased attention to the broader
social context in which children of depressed mothers develop. This investigation
examined the direct influences of maternal depression on child development, as
well as the role of contextual risks that may be particularly heightened in
families with depressed parents. Toddlers with depressed mothers evidenced
significantly more insecure attachments than did toddlers with nondisordered
mothers, and this difference was not accounted for by contextual risk. In
predicting child behavior problems, contextual risk was found to mediate the
relation between maternal depression and child behavior problems. Father-report
data on child behavior corroborated the mother report data. Results are discussed
in terms of the diversity of functioning in offspring of depressed caregivers
that can be attributed to varied levels of contextual risk accompanying
depression.
PMID- 9635226
TI - Mothering, fathering, and infant negativity as antecedents of boys' externalizing
problems and inhibition at age 3 years: differential susceptibility to rearing
experience?
AB - To examine the effects of infant negative emotionality and of mothering and
fathering during the toddler years on 3-year-old boys' externalizing problems and
inhibition, as well as explore the proposition that children vary in their
susceptibility to rearing influence, 125 first-born, Caucasian boys from
maritally intact families were studied. Results revealed that when infant
negativity is measured with objective, replicable, and discriminantly valid
procedures, no relation obtains between it and externalizing problems (nor
inhibition). Moreover, as hypothesized on the basis of prior work, parenting was
a stronger predictor of externalizing problems and inhibition in the case of
children who were highly negative as infants. Mothering proved a stronger
predictor of externalizing problems and fathering of inhibition, with more
negative mothering in the 2nd and 3rd year forecasting higher CBCL-externalizing
scores and less negative fathering in the 2nd and 3rd year and more positive
fathering in the 2nd year forecasting more inhibition at age 3 Implications of
these findings for studies of parental influence are considered.
PMID- 9635227
TI - Academic and emotional functioning in early adolescence: longitudinal relations,
patterns, and prediction by experience in middle school.
AB - Adopting a motivational perspective on adolescent development, these two
companion studies examined the longitudinal relations between early adolescents'
school motivation (competence beliefs and values), achievement, emotional
functioning (depressive symptoms and anger), and middle school perceptions using
both variable- and person-centered analytic techniques. Data were collected from
1041 adolescents and their parents at the beginning of seventh and the end of
eight grade in middle school. Controlling for demographic factors, regression
analyses in Study 1 showed reciprocal relations between school motivation and
positive emotional functioning over time. Furthermore, adolescents' perceptions
of the middle school learning environment (support for competence and autonomy,
quality of relationships with teachers) predicted their eighth grade motivation,
achievement, and emotional functioning after accounting for demographic and prior
adjustment measures. Cluster analyses in Study 2 revealed several different
patterns of school functioning and emotional functioning during seventh grade
that were stable over 2 years and that were predictably related to adolescents'
reports of their middle school environment. Discussion focuses on the
developmental significance of schooling for multiple adjustment outcomes during
adolescence.
PMID- 9635228
TI - Family systems and adolescent development: shared and nonshared risk and
protective factors in nondivorced and remarried families.
AB - The primary goal of this research is to increase the goodness-of-fit between the
theoretical tenets of family systems theory and quantitative methods used to test
systems hypotheses. A family systems perspective is applied to two specific
research questions concerning family influences on adolescent development: To
what extent are familial risk and protective factors for psychopathology and
competence shared or not shared by siblings and are different family relationship
patterns associated with optimal adolescent adjustment in nondivorced and
remarried families? Multirater and multimethod data from a national sample of 516
nondivorced and remarried families from the Nonshared Environment and Adolescent
Development (NEAD) project were examined using a combination of cluster, factor,
and regression analyses. Results indicated that the effects of an individual
relationship on adolescent adjustment is moderated by the larger network of
relationships in which it is embedded. Evidence for nonshared familial processes
in predicting adolescent psychopathology was also found but only in a subset of
families, and the mechanisms of influence were neither main effects nor linear,
as has been assumed by research to date. Results are discussed in light of family
systems models of relationship influence on development. These results illustrate
how family systems theory provides a specific example of contextualism as regards
the development of psychopathology in adolescence.
PMID- 9635229
TI - Integrating qualitative and quantitative methods in the study of developmental
psychopathology in context.
AB - Qualitative methods are well suited to advance the understanding of the role of
social context in the development of maladaptation and psychopathology. However,
they have not been widely used by developmental psychopathologists, despite being
utilized in related fields, particularly in the sociological study of crime and
delinquency. This article assesses the potential for the increased use of
qualitative methods in developmental psychopathology and addresses the challenges
involved in integrating them with quantitative research strategies. The interplay
of qualitative and quantitative methods in the study of juvenile delinquency is
reviewed for relevant lessons about both the utility and the difficulties of
integrating the two types of methods. The problem of assessing continuities and
discontinuities over the life course in patterns of antisocial behavior is
discussed as an example of the challenge of integrating methodological paradigms.
Schools of thought about qualitative methods and their relationship to
quantitative research paradigms are identified and compared. Examples are
discussed of narrative life history interviewing and qualitative observational
techniques and of recent research endeavors integrating these qualitative
techniques with quantitative data analyses.
PMID- 9635230
TI - The design and analysis of longitudinal studies of development and
psychopathology in context: statistical models and methodological
recommendations.
AB - The utility and flexibility of recent advances in statistical methods for the
quantitative analysis of developmental data--in particular, the methods of
individual growth modeling and survival analysis--are unquestioned by
methodologists, but have yet to have a major impact on empirical research within
the field of developmental psychopathology and elsewhere. In this paper, we show
how these new methods provide developmental psychopathologists with powerful ways
of answering their research questions about systematic changes over time in
individual behavior and about the occurrence and timing of life events. In the
first section, we present a descriptive overview of each method by illustrating
the types of research questions that each method can address, introducing the
statistical models, and commenting on methods of model fitting, estimation, and
interpretation. In the following three sections, we offer six concrete
recommendations for developmental psychopathologists hoping to use these methods.
First, we recommend that when designing studies, investigators should increase
the number of waves of data they collect and consider the use of accelerated
longitudinal designs. Second, we recommend that when selecting measurement
strategies, investigators should strive to collect equatable data prospectively
on all time-varying measures and should never standardize their measures before
analysis. Third, we recommend that when specifying statistical models,
researchers should consider a variety of alternative specifications for the time
predictor and should test for interactions among predictors, particularly
interactions between substantive predictors and time. Our goal throughout is to
show that these methods are essential tools for answering questions about life
span developmental processes in both normal and atypical populations and that
their proper use will help developmental psychopathologists and others illuminate
how important contextual variables contribute to various pathways of development.
PMID- 9635231
TI - Evaluation of a colorimetric method for detecting amphotericin B-resistant
Candida isolates.
AB - Substitution of Antibiotic Medium 3 for RPMI 1640 in the microdilution variant of
M27-A has been proven to permit detection of amphotericin B-resistant Candida
isolates. For this purpose, we have studied the utility of the colorimetric
indicator alamarBlue to simplify the former process because it is a readily
available commercial system. When used in combination with the NCCLS-recommended
RPMI 1640, alamarBlue did not improve the ability of RPMI 1640 to detect
resistant isolates. When used in combination with Antibiotic Medium 3, alamarBlue
reduced discrimination between susceptible and resistant isolates by increasing
the MIC of susceptible isolates. Thus, alamarBlue does not improve detection of
amphotericin B resistance among Candida isolates.
PMID- 9635232
TI - An increase in the number of polymorphonuclear leukocytes inoculated on shell
vial culture increases the sensitivity of this assay in the detection of
cytomegalovirus in the blood of immunocompromised patients.
AB - A prospective study was conducted comparing the sensitivity of the pp65
antigenemia assay (AGA) to that of the shell-vial culture (SVC) inoculated with
increasing quantities of polymorphonuclear leukocytes (PMNLs) in the detection of
cytomegalovirus (CMV) in peripheral blood. From the cellular suspension, three
SVCs were inoculated with 200,000, 400,000, and 800,000 PMNLs, respectively. Of
the 201 patients studied, 67 (31.9%) had positive results in one of the two
analytic tests (AGA or SVC). In this group, 13 (19.4%) presented a negative AGA
assay; 13 (19.4%) an AGA of 1; 13 (19.4%) an AGA of between 2 and 5; and 28
(41.8%) an AGA with a value > 6 PMNL-positive x 100,000 PMNLs. The SVC inoculated
with 200,000 PMNLs detected the presence of CMV in 42 cases (62.6%); 55 (82%)
with 400,000; and 64 (95.5%) with 800,000. Statistically significant differences
were observed between the isolation capacities of the SVC inoculated with 200,000
and 400,000, and the SVC inoculated with 800,000 PMNLs (p = 0.0001). In the
comparison of the overall sensitivity of the AGA with that of the SVC with
200,000, the AGA was found to be significantly more sensitive (p = 0.0052). When
comparing with the SVC with 400,000 PMNLs, the two techniques were found to be
equally sensitive; and in the comparison with the SVC with 800,000, the culture
displayed a greater detection sensitivity (p = 0.0023). According to these
results, it seems evident that the increase in the absolute number of PMNLs
inoculated in the SVC leads to a significant increase in the sensitivity of the
SVC in the detection of low-level viremia by CMV.
PMID- 9635233
TI - Mucoid encapsulated Enterococcus faecalis: an emerging morphotype isolated from
patients with urinary tract infections.
AB - Three strains of encapsulated Enterococcus faecalis, which produced highly mucoid
coalescing colonies on routine bacteriologic media, were isolated from urine
specimens of patients with urinary tract infection. Encapsulation could be
demonstrated through India ink preparations. The occurrence of this unusual
enterococcal colony morphotype, which resembles that of a Gram-negative
bacterium, may delay true identification.
PMID- 9635234
TI - Etiology and risk factors of 180 cases of native valve endocarditis. Report from
a 5-year national prospective survey in Slovak Republic.
AB - Risk factors, etiology, and outcome of 180 cases of infective endocarditis (IE)
in the Slovak Republic for 5 years were prospectively studied in a national
survey. According to the Duke Endocarditis Service Criteria (1994), 169 cases
were considered definitive and 21 possible/probable. The aortic valve was
infected in 46.7%, mitral in 47.2%, and tricuspidal/pulmonary in 6.1% of cases.
The majority of endocarditis cases was caused by Staphylococcus aureus and
coagulase-negative staphylococci (CNS) (33.3%); only 12.2% were due to viridans
streptococci; 11.7% were due to Enterococcus faecalis; 6.1% due to Haemophilus
spp.; 10.1% due to other organisms; and 26.7% were culture negative. Single
positive cultures of CNS were not considered clinically significant. More than
25% of 180 patients were older than 60 years. Rheumatic fever was a risk factor
in 35.5%, dental surgery in 20.5%, prior cardiosurgery in 7.8%, and neoplasia in
6.7%. All patients were treated with antimicrobials (average length of therapy
was 29.5 days) and 33.3% of patients also had surgery (valvular prosthesis
replacement). Forty (22.2%) died, and 140 (77.8%) survived at day 60 after the
diagnosis of endocarditis was made. All 40 deaths were attributable to infection.
Univariate analysis comparing deaths and survivors did not show significant
differences in most of the recorded risk factors between both groups, except age
> 60 (40.0% versus 21.4%, p < 0.05), staphylococcal etiology (55.0% versus 27.1%,
p < 0.04), and antibiotic therapy < 21 days (without surgery) (65.0% versus 3.6%,
p < 0.01). These risk factors were significantly more frequently associated with
deaths. Viridans streptococcal IE and surgical therapy in addition to antibiotics
were associated with lower mortality in comparison to staphylococcal endocarditis
(p < 0.045) or to cases treated with antibiotics only (p < 0.05). In comparison
to other nationally based surveys in Europe (Greece, Croatia, France), the
percentage of culture-negative endocarditis and spectrum of pathogens differed
significantly.
PMID- 9635235
TI - Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested
against over 28,000 recent clinical isolates from 200 medical centers in the
United States and Canada.
AB - A total of 200 medical center laboratories in the USA and Canada contributed
results of testing quinupristin-dalfopristin, a streptogramin combination
(formerly RP 59500 or Synercid), against 28,029 Gram-positive cocci. Standardized
tests [disk diffusion, broth microdilution, Etest (AB BIODISK, Solna, Sweden)]
were utilized and validated by concurrent quality control tests. Remarkable
agreement was obtained between test method results for characterizing the
collection by the important emerging resistances: 1) oxacillin resistance among
Staphylococcus aureus (41.0 to 43.7%); 2) vancomycin resistance among
Enterococcus faecium (50.0 to 52.0%); and 3) the penicillin nonsusceptible rate
for pneumococci (31.1% overall, with 10.6% at MICs of > or = 2 micrograms/mL).
The quinupristin-dalfopristin MIC90 for oxacillin-susceptible and -resistant S.
aureus was 0.5 microgram/mL and 1 microgram/mL, respectively. The quinupristin
dalfopristin MIC90 for vancomycin-resistant E. faecium was 1 microgram/mL, and
only 0.2% of isolates were resistant. Other Enterococcus species were generally
not susceptible to the streptogramin combination but were usually inhibited by
ampicillin (86 to 97% susceptible; MIC50, 1.0 microgram/mL) or vancomycin (86 to
95%; MIC50, 1.0 microgram/mL). Among all tested enterococci, the rate of
vancomycin resistance was 16.2%. The quinupristin-dalfopristin MIC90 (0.75
microgram/mL) for 4,626 tested Streptococcus pneumoniae strains was not
influenced by the penicillin or macrolide susceptibility patterns. When five
regions in the USA and Canada were analyzed for significant streptogramin and
other antimicrobial spectrum differences, only the Farwest region had lower
numbers of streptogramin-susceptible E. faecium. Canadian strains were generally
more susceptible to all drugs except chloramphenicol and doxycycline when tested
against E. faecalis (73% and 89% susceptible, respectively). The U.S. Southeast
region had S. pneumoniae strains less susceptible to macrolides (73%) but had
more susceptibility among E. faecium isolates tested against vancomycin and
ampicillin. The Northeast region of the USA had the greatest rate of vancomycin
resistance among enterococci. Strains retested by the monitor because of
quinupristin-dalfopristin resistance (MICs, > or = 4 micrograms/mL) were
generally not confirmed (2.2% validation), and only 0.2% of E. faecium isolates
were identified as truly resistant. The most common errors were: 1) species
misidentification (28.0%); 2) incorrect susceptibility results (65.6%); and 3)
mixed cultures (4.3%) tested by participants. Overall, quinupristin-dalfopristin
was consistently active (> or = 90% susceptible) against major Gram-positive
pathogens in North America, regardless of resistance patterns to other drug
classes and geographic location of their isolation.
PMID- 9635236
TI - Epidemiology, laboratory detection, and therapy of penicillin-resistant
streptococcal infections.
AB - Streptococci cause a wide range of infections in humans including respiratory
tract infections, endocarditis, meningitis, bacteremias, and skin and soft tissue
lesions. Mutations in the penicillin binding proteins target sites in these
organisms have recently caused resistance to penicillins and cephalosporins. The
passage of resistant genetic material from one streptococcal species to another
has been recognized as one of the mechanisms by which this resistance has
occurred and spread. Such resistance has been a particular problem in
Streptococcus pneumoniae and viridans group streptococci with penicillin
resistance levels in excess of 25%, now common in both groups of organisms
worldwide. Fourth-generation cephalosporins, with their enhanced antibacterial
activity against Gram-positive organisms (cefpirome > cefepime) and their
increased stability to the beta-lactamases produced by many bacterial species,
offer a new option for the treatment of potentially life-threatening infections
such as pneumococcal pneumonia and meningitis with or without bacteremia.
Clinical trials are currently in place to evaluate the role of these agents in
these, and other, indications of Gram-positive infections. Prior studies of
cefpirome therapy for infections caused by Streptococcus spp. were successful,
and recent expanded in vitro investigations profess a future for expanded use of
cefpirome to treat infections produced by several Gram-positive species.
PMID- 9635237
TI - Important and emerging beta-lactamase-mediated resistances in hospital-based
pathogens: the Amp C enzymes.
AB - Resistance to third-generation cephalosporins mediated by beta-lactamases is an
increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae
produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter
spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia
marcescens. Resistance via this mechanism has been shown to be statistically
correlated with the use of some third-generation cephalosporins, and the
infections caused by these stably derepressed enzyme-producing species seem to
occur most frequently in the seriously ill. More recently the genes encoding this
enzyme have been documented on plasmids capable of transfer into other species
such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability
and low affinity for the Amp C beta-lactamases and the ability to penetrate
rapidly into the periplasmic space of Gram-negative organisms, offer a viable
alternative in the treatment of these infections or as empiric regimens.
Furthermore, these compounds (example: cefpirome) possess greater potency against
the frequently occurring Gram-positive cocci such as oxacillin-susceptible
staphylococci and the streptococci (including some penicillin-resistant strains)
as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.
PMID- 9635238
TI - Empiric therapy of bacterial infections in patients with severe neutropenia.
AB - The urgent need to treat presumptive infections in neutropenic patients has meant
that initial therapy is empiric based on the pathogens most likely to be
responsible for the patient's rise in temperature or other symptoms of infection.
The spectrum of causative pathogens has changed over time and reflects the
availability and use of antimicrobial agents. Gram-positive organisms
predominated in the 1940s and onward until the widespread use of early
penicillins and cephalosporins effectively addressed this problem. The upsurge in
infections in the 1970s and 1980s caused by Gram-negative organisms, particularly
Pseudomonas aeruginosa, Escherichia coli and Klebsiella spp., has been supplanted
by a new wave of infections caused by Gram-positive organisms, this time
predominantly Staphylococcus aureus, Staphylococcus epidermidis, and the viridans
streptococci. The fourth-generation cephalosporins (cefpirome) among other broad
spectrum beta-lactams, by virtue of their enhanced antimicrobial activity against
Gram-positive pathogens and greater beta-lactamase stability, are promising
candidates for use in the empiric management of febrile episodes in neutropenic
patients. Early clinical trial results are promising and should lead the way for
further use of these compounds in this indication.
PMID- 9635239
TI - The role of fourth-generation cephalosporins in the treatment of serious
infectious diseases in hospitalized patients.
AB - For many years, the third-generation cephalosporins have been utilized in the
treatment of a broad range of infections. The reduction in the efficacy of these
antimicrobials in hospitals seen in recent years is a result of the development
of resistance to these compounds. This resistance, caused in part by the
production of beta-lactamases which can spread from species to species, has
intensified the search for alternative agents. Compared with third-generation
cephalosporins, fourth-generation cephalosporins possess enhanced activity
against Gram-positive organisms, excellent penetration into Gram-negative
bacilli, and are more stable against the activity of some beta-lactamases.
Accordingly, fourth-generation cephalosporins are attractive candidates to
replace third-generation cephalosporins for the treatment of many nosocomial
infections.
PMID- 9635240
TI - The clinical potential of fourth-generation cephalosporins.
PMID- 9635241
TI - In vitro bactericidal activity of cefpirome in combination with vancomycin
against Staphylococcus aureus and coagulase-negative Staphylococcus.
PMID- 9635242
TI - In vitro activities of six extended spectrum beta-lactam antibiotics against
clinically significant gram-negative bacteria.
PMID- 9635243
TI - Cefpirome: epidemiological survey in intensive care units and hematological units
in The Netherlands. The Dutch Study Group.
PMID- 9635244
TI - In vitro evaluation of cefpirome: an Australasian study of isolates from
intensive care unit and hematology/oncology patients. The Cefpirome Study Group.
PMID- 9635245
TI - Clinical studies of cefpirome in the treatment of urinary tract infections caused
by Enterococcus faecalis.
PMID- 9635246
TI - Cefpirome versus ceftazidime as empirical sepsis treatment. The Study Group.
PMID- 9635247
TI - In vitro activity of cefpirome against Streptococcus pneumoniae strains with
decreased susceptibility to cefotaxime.
PMID- 9635248
TI - Lung injury and degradation of extracellular matrix components by Aspergillus
fumigatus serine proteinase.
AB - Aspergillus fumigatus produces a variety of extracellular proteinases that are
believed to be virulence factors towards Aspergillus-related lung disease. Among
Aspergillus proteinases, the serine proteinase is thought to play a major
virulent role because of its widespread production. Nevertheless, evidence of
direct pulmonary injury caused by the A. fumigatus serine proteinase is still
lacking. The purpose of our work was: (1) to provide evidence for a pivotal role
of A. fumigatus serine proteinase in producing lung injury in an animal model,
and (2) to investigate the broadness of the substrate specificity of the
proteinase towards extracellular matrix components. To achieve this aim, the
proteinase from an A. fumigatus strain isolated from human airways was purified
by a four-step procedure, including cation exchange and hydrophobic interaction.
High-performance capillary electrophoresis, SDS-PAGE, determination of K(m)
towards synthetic substrates, and inhibitory studies were used to further
characterize the A. fumigatus serine proteinase. With reference to extracellular
matrix components, the A. fumigatus serine proteinase was shown to degrade human
lung elastin at a higher rate than an equimolar amount of human neutrophil
elastase. Human lung collagen, type I and type III collagens, as well as
fibronectin, were quickly digested by the A. fumigatus serine proteinase.
Finally, mice intratracheally injected with the proteinase showed a significant
degree of lower respiratory tract destruction. We conclude that the A. fumigatus
serine proteinase is capable per se of hydrolyzing the major structural barriers
of the lung.
PMID- 9635249
TI - Differential expression of arginase and iNOS in the lung in sepsis.
AB - The primary metabolic fates of L-arginine are conversion to L-citrulline by
nitric oxide synthase (NOS) and to L-ornithine by arginase. In the lung, arginine
utilization is increased after the inducible form of NOS (iNOS) is expressed
during inflammation. The expression of arginase in normal lung and after sepsis,
and its potential relationships with iNOS, however, are not known. Since arginase
and iNOS share the substrate L-arginine, we tested the hypothesis that lung
arginase would be co-induced with iNOS in sepsis and its cellular distribution
would be related to that of iNOS in the lung. Lungs from cecal ligation and
puncture (CLP) and sham-operated (S) rats were harvested 6 or 16 hours after the
procedures. Lung wet-to-dry weight ratio, myeloperoxidase content, and lipid
peroxidation products were measured as indices of lung injury. Western blot
analyses were performed with polyclonal antibodies against two isoforms of rat
arginase (I and II) and iNOS. Additional lungs from CLP and S animals were
inflation-fixed for immunohistochemistry using the same antibodies. We found by
Western blot that arginase II at 39 kDa was the main isoform present in normal
rat lung. The enzyme was distributed diffusely in alveolar and bronchial
epithelial cells, endothelial cells, and alveolar macrophages. After CLP,
arginase II was almost undetectable in rat lungs at 16 hours. In contrast, in
normal lung, the iNOS was not detectable by Western blot or immunohistochemistry.
After CLP, strong expression of iNOS was found in similar cell types to arginase
II. These data demonstrate loss of constitutive expression of arginase II in rat
lung as iNOS is upregulated by the response to sepsis.
PMID- 9635250
TI - Kinetic characterization of bovine lung low-molecular-weight protein tyrosine
phosphatase.
AB - Protein tyrosine phosphatase is an important class of enzymes that plays an
essential role in the cellular proliferation, differentiation, and oncogenesis.
In this paper we report characterization of a low-molecular-weight protein
tyrosine phosphatase purified from bovine lung. The enzyme activity was
essentially independent of metal ions and sensitive to sulfhydryl reagents. Both
vanadate and inorganic phosphate are competitive inhibitors, with Ki values of
0.38 microM and 0.28 mM, respectively. Besides p-nitrophenyl phosphate, the
enzyme was also able to efficiently hydrolyze tyrosine phosphate, beta-naphthyl
phosphate, and flavine mononucleotide.
PMID- 9635251
TI - Posttreatment with eicosatetraynoic acid decreases lung edema in guinea pigs
exposed to phosgene: the role of leukotrienes.
AB - Acetylenic acids such as 5,8,11,14-eicosatetraynoic acid (ETYA), have been shown
to be effective in preventing pulmonary edema formation (PEF). In phosgene
exposed guinea pigs, we examined the effects of ETYA on PEF, measured as real
time lung weight gain (lwg). Pulmonary artery pressure (Ppa), airway pressure
(Paw), perfusate leukotrienes (LT) C4/D4/E4/B4, and lung tissue lipid
peroxidation (TBARS) were measured using the isolated, buffer-perfused lung
model. Guinea pigs were challenged to 175 mg/m3 (44 ppm) phosgene for 10 minutes
giving a concentration x time product of 1750 mg.min/m3 (437 ppm.min). Five
minutes after removal from the exposure chamber, guinea pigs were treated, i.p.,
with 200 microL of 100 microM ETYA. 200 microL of 50 microM ETYA was added to the
perfusate every 40 minutes, beginning at 60 minutes after start of exposure (t =
0). There were four groups in this study: air-treated, phosgene-exposed, ETYA
posttreated + phosgene, and ETYA-posttreated + air ETYA-posttreated + phosgene
guinea pigs had significantly lower Ppa (P = .006), Paw (P = .009), and lwg (P =
.016) compared with phosgene-exposed animals. Phosgene exposure reduced LTB4
compared with air-treated controls (P = .09). ETYA-posttreatment + phosgene had
significantly increased perfusate LTB4 (P = .0006) compared with phosgene
exposure only group. Total perfusate, LTC4 + LTD4 + LTE4, was not different
between phosgene-exposed, air-treated or ETYA-posttreatment + phosgene over time.
Posttreatment with ETYA significantly lowered TBARS formation, 206 +/- 13 versus
285 +/- 23 nmol/mg protein (P = .016), compared with phosgene-exposed lungs.
Paradoxically, ETYA posttreatment decreased PEF and lipid peroxidation, but
increased sulfidopeptide LT release from the lung during perfusion. We conclude
that LTC4/D4/E4, and B4, may play different roles than previously thought for PEF
in the isolated perfused lung model.
PMID- 9635252
TI - Silica deposition in the lung during epithelial injury potentiates fibrosis and
increases particle translocation to lymph nodes.
AB - Increased respiratory disease and daily mortality rates are associated with
higher levels of fine particulate air pollutants. We examined the possibility
that deposition of particles to previously injured lungs might accentuate
pulmonary damage, by investigating how the lung handled silica deposited during a
phase of epithelial injury. A low dose of intratracheal (i.t.) bleomycin (BL) was
used to induce epithelial damage in mice; 3 days later, 0.2 mg silica was
instilled. Lung injury, measured by cell numbers and protein levels in
bronchoalveolar lavage, was increased at 1 week and many silica particles
translocated to the interstitium. At 12 weeks, the silica plus BL group showed
increased pulmonary fibrosis biochemically and morphologically, and had
significantly higher retained-silica content in the lung. In addition, these mice
showed enlarged hilar lymph nodes with many granulomas-containing macrophages and
silica. The results indicate that instillation of fine particulates to the
alveoli at a time of epithelial damage potentiates the lung injury and increases
translocation of particles to the interstitium. In the case of silica, deposition
of particles into injured lungs resulted in increased fibrosis. The demonstration
of enhanced translocation of silica to lymph nodes suggests that inhaled fine
particulates may induce more distal effects following transport across an injured
epithelium and subsequent entrance to the lymphatic system.
PMID- 9635253
TI - Adhesive characteristics of type II pneumocyte subpopulations from saline- and
silica-treated rats.
AB - Alveolar epithelial cells isolated from silica-treated rat lungs provide a system
for the in vitro study of repair mechanisms. In studies of type II cell
interactions with the extracellular matrix, we observed that type IIB pneumocytes
from silica-treated rats adhered to tissue culture plastic more readily than do
normal type II cells. This paper examines the adhesion characteristics of IIA and
IIB cells and their modulation by divalent cations. We describe differences in
the adhesive behavior of two subpopulations of freshly isolated type II
pneumocytes from saline- and silica-treated rats. The observations have
implications for repair and tissue remodeling in the lung.
PMID- 9635254
TI - Alterations in the expression of chemokine mRNA levels in fibrosis-resistant and
sensitive mice after thoracic irradiation.
AB - Fibrosis, characterized by the accumulation of collagen, is a consequence of a
chronic inflammatory response. The purpose of this study was to determine if the
mRNA expression of the chemokines, lymphotactin (Ltn), RANTES, eotaxin,
macrophage inflammatory protein (MIP)-1 alpha, -1 beta, and -2, interferon
inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1), are
altered during the development of radiation-induced pneumonitis and fibrosis.
Further, we wished to determine if these changes differ between two strains of
mice that vary in their sensitivity to radiation fibrosis. Fibrosis-sensitive
(C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single
dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized
utilizing RNase protection assays. Data were quantified by phosphorimaging and
results normalized to a constituitively expressed mRNA L32. 8 weeks post
irradiation most chemokines measured were elevated to varying degrees. The degree
of elevation of each chemokine was identical in both strains. This suggested that
chemotactic activity for neutrophils, macrophages, and lymphocytes were occurring
during pneumonitis. By 26 weeks post-irradiation, messages encoding Ltn, RANTES,
IP-10, and MCP-1 were elevated only in fibrosis sensitive (C57BL/6) mice. In situ
hybridization demonstrated that MCP-1 and RANTES transcripts were produced
predominantly from macrophages and lymphocytes. These studies suggest that
lymphocytic recruitment and activation are key components of radiation-induced
fibrosis.
PMID- 9635255
TI - Effect of developmental age and hyperoxia exposure on kinase and phosphatase
activities in newborn rat lungs.
AB - To better understand the biochemical events accompanying lung alveolarization and
development, we studied the specific activity of the cAMP-dependent protein
kinase (PKA) and the type 2A protein phosphastase (PP2A), and the activity and
protein content of the calcium- and lipid-dependent protein kinase (PKC) in
cytosolic preparations of lungs. Lungs were obtained from rat pups on day 2 of
life and on days 7, 14, and 27 from pups exposed to hyperoxia (> 95% O2, days 4
14; 65% O2 days 15-27) or normoxia from day 4 onwards. There were no significant
changes in PKA specific activity with developmental age or hyperoxic exposure.
PKC specific activity increased significantly (P < .05) in normoxic animals from
day 2 (64 +/- 13.5 pmol phosphate released/min/mg protein) to day 14 (105 +/- 9).
The increase was sustained to day 27. There was no effect on PKC activity due to
hyperoxia alone (ANOVA). This increase in PKC activity was accompanied by an
increase in the mass of the delta, epsilon and zeta isoforms of PKC in normoxic
pups. The gamma isoform of PKC was undetectable in all samples whereas the alpha
and beta isoforms were detectable but showed no changes with developmental age.
PP2A specific activity increased significantly (P < .05) from 13.3 +/- 0.5 nmol
phosphate released/min/mg protein on day 2 to 17.7 +/- 0.9 on day 7 in normoxic
pups, then returned to day 2 level at advanced developmental age. Hyperoxia
exposure prevented the increase in enzyme activity observed on day 7 in normoxic
animals. These data suggest that protein phosphorylation may be one mechanism by
which alveolarization is regulated in developing lungs.
PMID- 9635256
TI - Expression of nitric oxide synthase isoforms in normal human tracheobronchial
epithelial cells in vitro: dependence on retinoic acid and the state of
differentiation.
AB - The retinoic acid (RA) and differentiation dependence of constitutive expression
of the nitric oxide synthase (NOS) isoforms, iNOS, eNOS, and bNOS, was examined
by reverse transcriptase polymerase chain recitation (RT-PCR) in cultured,
normal, human, tracheobronchial epithelial (NHTBE) cells. In the presence of RA
(RA+), early passage NHTBE cells grown in air-liquid interface (ALI) cultures
undergo mucous differentiation; in the absence of RA (RA-), they undergo
metaplastic squamous differentiation. Under both conditions the respective
differentiated phenotype develops around day 10 of culture. We found that iNOS
mRNA levels were much higher in RA+ cultures, expressing the mucous phenotype,
than in RA- cultures, expressing the metaplastic squamous phenotype. In contrast,
eNOS mRNA levels were much higher in RA- cultures than in RA+ cultures.
Expression of bNOS was not significantly affected by the RA status. The pattern
of expression of NOS isoforms was then studied during the course of development
of the two cellular phenotypes. During the early stages of differentiation,
expression of iNOS (RA+) and eNOS (RA-) was very low, indicating that the
expression of these two isoforms was not only dependent on the presence or
absence of RA, but also on the degree of differentiation. The differentiation
dependence of bNOS mRNA was less obvious. Four days of RA treatment of RA-
cultures, which reverses the squamous phenotype and restores mucous
differentiation, induced iNOS expression in a concentration-dependent manner.
eNOS expression was depressed by 10(-8) M RA, while bNOS mRNA levels were
slightly reduced by 10(-6) M RA. No NOS proteins were detected in unstimulated
RA+ and RA- cultures. iNOS protein was induced by cytokine treatment in RA+
cultures, in contrast to eNOS and bNOS protein levels, which were unaffected. Our
studies show that constitutive expression of the NOS isoforms is differentially
regulated and that iNOS and eNOS mRNA levels are dependent on the stage of mucous
and squamous differentiation, respectively. bNOS expression was only marginally
affected by the RA or differentiation status.
PMID- 9635257
TI - Pregnancy plans despite AIDS risk.
PMID- 9635258
TI - Is Medicaid pronatalist? The effect of eligibility expansions on abortions and
births.
AB - CONTEXT: Income thresholds for Medicaid eligibility for pregnant women were
raised in two phases between 1987 and 1991. During roughly the same period, the
U.S. fertility rate rose and the abortion rate declined; changes were
particularly marked among young women, raising the possibility that fertility
increases were related to Medicaid expansions. METHODS: Pooled time-series cross
section regressions were used to examine the effects of the Medicaid eligibility
expansions in 15 states on rates of abortions and births among unmarried women
aged 19-27 with 12 or fewer years of schooling. Abortion data came from the
National Center for Health Statistics or state health departments and were
aggregated by women's age, race, marital status and schooling; data on births
were from national natality tapes. RESULTS: The Medicaid expansions were
associated with a 5% increase in the birthrate among white women, but did not
influence the rate among black women. Overall, no effect on the abortion rate was
evident, but in analyses restricted to a subsample of eight states with the most
complete abortion data, the rate among white women showed a significant decline
after the second phase of expansions. CONCLUSIONS: Subsidized health care for low
income pregnant women in these 15 states may have encouraged white women to have
more children than they would have without coverage.
PMID- 9635259
TI - Contraceptive practices and trends in France.
AB - CONTEXT: Contraceptive use has been legal in France for the past 30 years, and
patterns of use changed substantially from the 1960s to the 1980s. Given the
rapidity with which use patterns change and the possible impact of rising concern
about infection with HIV and other sexually transmitted diseases, it is important
to determine trends of contraceptive practice into the 1990s. METHODS: A total of
5,900 French households were selected in 1994 for inclusion in the Fertility and
Family Survey. Respondents were questioned about their contraceptive use patterns
and family formation status. The results were compared with those of comparable
surveys conducted in 1978 and 1988. RESULTS: Two-thirds of French women used some
form of reversible contraceptive method in 1994. Oral contraceptive use has grown
steadily in France: About 40% of women aged 20-44 reported using the pill alone
or combined with another method in 1994, compared with 34% in 1988 and 28% in
1978. Condom use has also been on the rise: Nearly 8% of women were using condoms
alone or combined with another method in 1994, up from 5% in 1988 and 6% in 1978.
IUD use has declined from 19% in 1988 to 16% in 1994, and both male and female
sterilizations remain rare. CONCLUSIONS: Contraceptive behavior in France appears
unique among developed countries, with fairly high levels of oral contraceptive
use--even among older women--relatively high levels of IUD use and little
reliance on either male or female sterilization. As with other countries,
however, condom use has climbed in recent years, and is especially common at
first intercourse.
PMID- 9635260
TI - Gender and ethnic differences in the timing of first sexual intercourse.
AB - CONTEXT: Whether the effect of gender on the risk of first intercourse in
influenced by adolescents ethnicity has received limited attention in research on
age at first sex. Such information could provide a more complete understanding of
adolescent sexual behavior. METHODS: Life-table analysis using data from a
population-based, ethnically diverse sample of 87/Los Angeles County youths was
employed to estimate the median age at first sex for each gender-and-ethnicity
group. Multivariate analysis using proportional hazards techniques was conducted
to determine the relative risk of sexual activity among teenagers in each group.
RESULTS: Overall, the teenagers in the sample had a median age at first sex of
16.9 years. Black males had the lowest observed median (15.0), and Asian American
males the highest (18.1); white and Hispanic males, and white and black females,
reported similar ages (about 16.5 years). Hispanic and Asian American females had
rates of first sex about half that of white females, although these protective
effects were explained by differences in family structure. Even after controlling
for background characteristics, black males had rates of first sex that were
about 3-5 times the rates of the other gender-and-ethnicity groups. In addition,
Asian American males were less likely than Hispanic males to be sexually
experienced, and Hispanic males had almost twice the rates of sexual activity of
Hispanic females. CONCLUSIONS: Socioeconomic conditions account for ethnic
differences among females in the age at first sex, and cultural influences may
contribute to the difference between Hispanic males and females; explanations for
black males, however, remain elusive.
PMID- 9635261
TI - Measuring the extent of abortion underreporting in the 1995 National Survey of
Family Growth.
AB - CONTEXT: Induced abortions are often severely underreported in national surveys,
hampering the estimation and analysis of unintended pregnancies. To improve the
level of abortion reporting, the 1995 National Survey of Family Growth (NSFG)
incorporated new interview and self-report procedures, as well as a monetary
incentive to respondents. METHODS: The weighted numbers of abortions reported in
the main interview of the 1995 NSFG (Cycle 5), in the self-report and in the two
procedures combined are compared with abortion estimates from The Alan Guttmacher
Institute. The Cycle 5 estimates are also compared with estimates from previous
cycles of the NSFG. RESULTS: The self-report produces better reporting than the
main interview, but combining data from the two procedures yields the highest
count of abortions. For the period 1991-1994, the level of reporting is 45% in
the main interview, 52% in the self-report and 59% when the two methods are
combined. The level of abortion reporting in the combined data ranges from 40%
for women with an income less than the federal poverty level to more than 75%
among women who were older than 35, those who were married at the time of their
abortion and those with an income above 200% of the poverty level. The
completeness of abortion reporting in the main interview of Cycle 5, though
indicating a remarkable improvement over reporting in Cycle 4, is comparable to
the levels in Cycles 2 and 3. CONCLUSIONS: The usefulness of the NSFG remains
extremely limited for analyses involving unintended pregnancy and abortion.
PMID- 9635262
TI - Factors influencing the delivery of abortion services in Ontario: a descriptive
study.
AB - CONTEXT: Although Canadian women have had the right to obtain legal induced
abortions for the past decade, access to the procedure is still limited and
controversial in many areas. METHODS: Chiefs of obstetrics and gynecology, chiefs
of staff, directors of nursing and other health professionals at 163 general
hospitals in Ontario, Canada, were asked to provide information on issues
concerning the availability of abortion services of their facility. The hospital
participation rate was 97% and the individual response rate was 75%. RESULTS:
Nearly one-half (48%) of hospitals perform abortions. Approximately 36% of these
hospitals do so up to a maximum gestational age of 12 weeks, 23% to a maximum of
13-16 weeks, 37% to a maximum of 17-20 weeks and 4% at greater than 20 weeks.
Hospital factors, including resources and policies, did not significantly
influence whether abortions are provided. However, these factors did affect the
number performed, whether there were gestational limitations and the choice of
procedure. About 13% of provider hospitals indicated that staff training
contributes to the existence of gestational age limits, and 24% said that it
directly influences procedure choice. Only 18% of hospitals reported that their
physicians have received additional training outside of their medical school or
medical residency education to learn abortion techniques or to gain new skills.
Forty-five percent of hospitals that provide abortions had experienced harassment
within the past two years, and 15% reported that this harassment has directly
affected their staff members' willingness to provide abortions. CONCLUSION: Based
upon the provision of obstetric care, many hospitals in Ontario that are capable
of offering abortion services do not. Some of the reasons for this failure are
related to the procedure itself, while others may be related to resource issues
that affect the delivery of other medical services as well. Variation in the
availability of abortions is due to a shortage of clinicians performing the
procedure, and training directly influences gestational limits and procedural
choices.
PMID- 9635263
TI - Family planning service provision in rural areas: a survey in Washington State.
AB - CONTEXT: Women in rural areas are highly dependent on public clinics for family
planning services, yet little information has been collected on rural family
planning providers, especially on their funding and operation. METHODS: All 31
family planning clinic sites in rural Washington State were surveyed about their
sponsorship, staffing, service provision and population coverage. RESULTS: Clinic
sites were located in 25 of the 53 discrete rural health service areas of
Washington State. While the three wealthiest areas had clinics, eight of the
poorest areas had no clinics. Eight clinics were Planned Parenthood affiliates,
eight were private freestanding clinics and 15 were local health department
sites. Clinic sites were small (with the equivalent of 2.4 full-time staff
members, on average) and offered a mean of 18 of 43 potential reproductive and
women's health care services; general primary care services were rarely provided.
Only one clinic offered abortions. CONCLUSION: Family planning clinics in rural
Washington State offer an important but limited number of services. Many rural
areas have no local family planning clinic. Given these clinics' reliance on
federal and state funding, decreased public support might seriously impair family
planning provision in rural areas.
PMID- 9635264
TI - Studying parental involvement in school-based sex education: lessons learned.
PMID- 9635265
TI - Approaching clinical application of xenotransplantation.
PMID- 9635266
TI - Surgical correction of hypertrophic obstructive cardiomyopathy: seventeen-year
Green Lane experience.
AB - Between 1977 and 1994, 42 patients were treated surgically for hypertrophic
obstructive cardiomyopathy (HOCM). Patients have been followed up between 2
months to 17 years, mean of 107 months. There were 26 (62%) males and 16 (38%)
females. There was only one pediatric case. There was no correlating factor among
the ethnic groups (Maori, European, Indian, Asian, etc.). Family history was
noted in 12% of the cases. Seventy-one percent of patients had aortic/left
ventricular (LV) combined approach while 29% had aortic approach alone at the
time of surgery. Five patients underwent other procedures, along with coronary
artery bypass grafting in 3, mitral valve replacement in 1, and aortic valve
replacement in 1. Persistent postoperative arrhythmias were found in 7 cases,
atrial fibrillation (AF) in 3, and left bundle branch block in 4.
PMID- 9635267
TI - Sinus of Valsalva aneurysms: 20 years' experience.
AB - BACKGROUND: Aneurysms of sinus of Valsalva are rare. Here, we analyze
retrospectively patients operated on at our center during the last 20 years.
PATIENTS AND METHODS: One hundred four cases of congential aneurysm of sinus of
Valsalva were operated upon between January 1977 and April 1996. Only 12
aneurysms were unruptured. The majority (76.9%) arose from the right coronary
sinus. The right ventricle was the most common chamber of rupture (58.6%).
Ventricular septal defect was associated in 46 patients (44.2%), of which 28
(60.9%) were supracristal. Ventricular septal defect was more common in aneurysms
arising from the right coronary sinus (91.3%). Aortic incompetence was found in
45 patients (43.3%). The defect was closed through the aortic root alone in 24
patients (23.1%) and through both the aortic root and the chamber of rupture in
the remaining 80 patients. Six patients underwent aortic valve repair, and 21 an
aortic valve replacement. RESULTS: There were two hospital deaths (1.92%).
Morbidities were few. Follow-up ranged from 1 to 20 years (mean 8.2 +/- 1.1).
There was one late noncardiac death, and in the majority, the long-term follow-up
was uneventful. CONCLUSION: Surgery for aneurysm of sinus of Valsalva yields
gratifying results, and it should be undertaken as soon as the condition is
diagnosed.
PMID- 9635268
TI - Rapid recovery of octogenarians following coronary artery bypass grafting.
AB - BACKGROUND: Rapid recovery protocols for coronary artery bypass grafting (CABG)
have resulted in major decreases in postoperative hospital length of stay (LOS)
when applied to younger patients undergoing elective procedures. However, the
effectiveness of rapid recovery protocols when applied to octogenarians has not
been thoroughly studied. METHODS: Thirty-seven consecutive octogenarians
underwent isolated CABG utilizing cardiopulmonary bypass (CPB). A protocol
emphasizing preoperative placement of the intra-aortic balloon pump, reduced CPB
time, early extubation, perioperative steroids, thyroid hormone, and aggressive
postoperative diuresis was used. RESULTS: The 30-day operative mortality for the
entire series was 5.4%. Twenty-five patients (71%, group I) were discharged in <
10 days postoperatively (average LOS of 6.3 +/- 1.6 days), while ten patients
(29%, group II) were discharged at 10 or more days postoperatively (average LOS
of 20.3 +/- 8.0, p < 0.001). Patients in group II were found to have a higher
incidence of obesity (50% vs 4%, p < 0.01), symptomatic peripheral vascular
disease (60% vs 8%, p < 0.01), and preoperative ambulatory difficulties (50% vs
0%, p < 0.01). The incidence of complications was 31% for the entire series, with
no differences between the groups. CONCLUSION: Octogenarians performed well under
a rapid recovery protocol, with 71% being discharged in < 10 days
postoperatively, while patients with obesity, symptomatic peripheral vascular
disease, and ambulatory difficulties rehabilitated more slowly.
PMID- 9635269
TI - Right heart growth after the Bjork connection in tricuspid atresia.
AB - BACKGROUND: Atrioventricular (Bjork) connection used for the correction of
tricuspid atresia has become of little more than historical interest. However,
the optimal form of management of patients undergoing this repair still requires
continued assessment of the long-term outcome. We review our experience with
valveless atrioventricular connection focusing on the morphological changes seen
in the heart chambers. METHODS: Between October 1978 and March 1986, seven
patients with tricuspid atresia having concordant ventriculoarterial connection
underwent atrioventricular connection. Configuration of the surgical connection
included Dacron extracardiac conduit without valve insertion. End-diastolic
volumes were calculated in the respective heart chambers. A group of patients
undergoing atriopulmonary connection was used as control subjects. RESULTS: The
diminutive right ventricle showed conspicuous growth at 1.1 +/- 1.1 years after
the initial repair, with the end-diastolic volume index increasing from 25.0 +/-
8.7% of normal value at a preoperative state to 80.4 +/- 31.1% of normal value
postoperatively. Further operation was done in three patients because of the
obstructive atrioventricular pathway. At reoperation, reconstruction of the
connection with an addition of either atriopulmonary or cavopulmonary anastomosis
afforded clinical improvement in our series. CONCLUSIONS: This study suggests
that volume load resulting from the widely patent atrioventricular connection
combined with backward regurgitation affects the development of young heart
muscle of the right ventricle. The optimal choice of surgical strategy should be
made at reintervention through recognition of the particular postsurgical
anatomy.
PMID- 9635270
TI - Variations in annuloplasty ring and sizer dimensions may alter outcome in mitral
valve repair.
AB - BACKGROUND AND AIMS: Sizing the mitral annulus remains one of the more subjective
areas of annuloplasty surgery. We compared the dimensions of annuloplasty rings
to annuloplasty sizers and to human mitral valve annuli to determine whether any
discrepancies exist that might impact repair results. METHODS: The anterior and
posterior length of rigid rings, flexible rings, and corresponding sizers were
measured. The ratio of the anterior length to the total length was calculated
(A/T ratio) and compared to normal human ratios. RESULTS: Nearly all rings had
A/T ratios between 30% and 35% (except for the 32-mm rigid ring at 37.5%). For
both rigid and flexible rings, the ring A/T ratios and the sizer A/T ratios
differed significantly (except for the 28-mm rigid ring and sizer). In comparison
to the average human A/T ratio (36.6%), the ratio for most rings was
significantly lower. CONCLUSIONS: The mismatch between rings and sizers results
in three possible scenarios: the length of the anterior portion of the ring can
be equal to, smaller than, or larger than the anterior portion of the sizer. The
clinical implications are that the valve could become stenotic when the ring is
implanted or that the anterior portion of the annulus could be altered (stretched
or buckled). We feel that to assure improved long-term results, more accurate
matching of sizers to rings is essential and that better matching to normal human
anatomical ratios would be ideal.
PMID- 9635271
TI - Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to
epsilon aminocaproic acid and placebo.
AB - Perioperative bleeding following coronary artery bypass grafting (CABG) is
associated with increased blood product usage. Although aprotonin is effective in
reducing perioperative blood loss, excessive cost prohibits routine utilization.
Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive
antifibrinolytic agents, which, when given prophylactically, may reduce blood
loss. The present study was undertaken to compare the efficacy of TA and EACA in
reducing perioperative blood loss. METHODS: The study population consisted of
first-time CABG patients. Patients were allocated in a prospective double-blind
fashion: (1) group EACA (loading dose 15 mg/kg, continuous infusion 10 mg/kg per
hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous
infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of
normal saline for 6 hours, N = 19). RESULTS: Treatment groups were similar
preoperatively. No significant difference in intraoperative blood loss or
perioperative use of blood products was noted. D-dimer concentration was elevated
in the control group compared to the EACA and TA groups (p < 0.05). Group TA had
less postoperative blood loss than the EACA and control groups at 6 and 12 hours
postoperatively (p < 0.05). TA had reduced total blood loss (600 +/- 49 mL)
postoperatively compared to EACA (961 +/- 148 mL) and control (1060 +/- 127 mL, p
< 0.05). CONCLUSION: TA and EACA effectively inhibited fibrinolytic activity
intraoperatively and throughout the first 24 hours postoperatively. TA was more
effective in reducing blood loss postoperatively following CABG. This suggests
that TA may be beneficial as an effective and inexpensive antifibrinolytic in
first-time CABG patients.
PMID- 9635272
TI - Hypoplasia of the posterior leaflet as a rare cause of congenital mitral
insufficiency.
AB - A rare case of congenital mitral insufficiency characterized by the hypoplasia of
the posterior leaflet is reported. At operation, the mitral valve was
successfully repaired by a ring annuloplasty, which created a satisfactory
surface of coaptation between the anterior leaflet and the bulky posterior
muscular structure. The presence of this posterior muscular structure represents
a developmental arrest at the stage of conversion from muscular chordae and
leaflets to thin connective structures.
PMID- 9635273
TI - Comparison of different regimens of electrical stimulation applied to
nonmobilized and newly mobilized latissimus dorsi muscle.
AB - We investigated the possibility of preventing further aggravation of muscle
ischemia and necrosis in newly mobilized, unconditioned latissimus dorsi muscle
(LDM) by utilizing short increments of stimulation with intervening rest periods.
Adult St. Croix sheep (N = 12) weighing 30 +/- 8 kg were used in this study.
Fatigue tests (30 min) using different stimulation regimens before and after LDM
mobilization were performed on all animals; the length of time to return to
baseline levels was also measured. Our investigation yielded results that
contradict the conventional wisdom that any electrical stimulation damages newly
mobilized LDM and will cause a considerable decrease in contractile force (CF).
Stimulation regimens using continuous contractions at 30 and 60 contractions per
minute (CPM) for 30 minutes were damaging to the LDM. CF also dropped
significantly and returned slowly to baseline values: at 60 CPM, CF dropped to 50
+/- 4% and did not return to baseline even after 90 minutes of rest; at 30 CPM,
CF dropped to 61 +/- 4% and baseline was restored after 80 minutes of rest.
Electrical stimulation using continuous contractions at a slower rate (15 CPM)
was tolerable, although a 23% decrease in CF was noted (p < 0.05 when compared to
60 CPM). These results did not satisfy us that such a regimen would be useful for
cardiac assistance immediately after cardiomyoplasty. The work-rest regimen at 30
CPM also gave poor results: CF decreased to 75 +/- 2% and baseline was restored
after 80 minutes of rest. Promising results were seen when utilizing a work-rest
regimen at 15 CPM. The newly mobilized LDM showed no visible signs of fatigue: CF
decreased minimally to 92 +/- 3% (p < 0.05 when compared to 30 CPM), and light
microscopic analysis of biopsies revealed no morphological damage exceeding that
typically seen after subtotal mobilization. Such results open avenues for future
investigations: beginning electrical stimulation immediately after
cardiomyoplasty (using a single impulse and a slow rate of contraction);
decreasing the length of time necessary to obtain full cardiac assistance; and
beginning partial cardiac assistance immediately after cardiomyoplasty (if
needed) for approximately 30 minutes several times a day.
PMID- 9635274
TI - Hemodynamic response to in situ latissimus dorsi muscle stimulation: implications
in dynamic cardiomyoplasty.
AB - Dynamic cardiomyoplasty (DCM) involves the electrical stimulation of a pedicled
latissimus dorsi muscle flap wrapped around the falling ventricle as a means of
cardiac assist. To further elucidate a potential neurohumoral mechanism for
improvement of cardiac output after myoplasty, we evaluated the hemodynamic
effects of in situ stimulation of the latissimus dorsi muscle (in the absence of
cardiomyoplasty). In seven mongrel dogs, a nerve cuff electrode (Medtronic 6901)
was placed around the left thoracodorsal nerve (TDN). This was attached to a
pulse generator (Medtronic, Itrel 7420), delivering a 4.0 volt, 0.19 second on,
0.81 second off, 33 Hz, 210 microsecond pulse width, cyclic bursts similar to
that used in DCM. Stroke volume index (SVI) and other hemodynamic parameters as
well as plasma norepinephrine (NE) levels were measured at five stages: baseline,
stimulator on at 0, 2, and 5 minutes, and stimulator off at 30 minutes after. The
animals were then subjected to 4 weeks of rapid pacing at 240 beats/min
(Medtronic 8329) to induce heart failure, and as the rapid pacing was
discontinued, measurements were repeated as above. After rapid pacing, cardiac
function was significantly depressed, and NE was elevated (133 +/- 69 versus 500
+/- 353 pg/mL, p < 0.05). In the normal hearts, TDN stimulation increased SVI,
heart rate, systemic pressure, and NE levels. In heart failure, however, no
significant changes in cardiac function and NE levels were noted. In conclusion,
our data indicate that in the normal hearts, afferent impulses from TDN
stimulation alone may augment cardiac function by means of a neurohumoral effect
that is not seen in severe heart failure. The implications of these findings in
DCM are discussed.
PMID- 9635275
TI - To know chalk from cheese.
PMID- 9635276
TI - Myosin light chain phosphatase: subunit composition, interactions and regulation.
AB - This review has presented some of the recent data on myosin phosphatase from
smooth muscle. Although it is not conclusive, it is likely that most of the
myosin phosphatase activity is represented by a holoenzyme composed of three
subunits. These are: a catalytic subunit of 38 kDa of the type 1 phosphatase,
probably the delta isoform (i.e. PP1c delta); a subunit of about 20 kDa whose
function is not established; and a larger subunit that is thought to act as a
target subunit. This is termed the myosin phosphatase target subunit, MYPT.
Various isoforms of MYPT exist and the relatively minor distinctions are in the C
terminal leucine zipper motifs and/or with inserts in the central region. Many
regions of the molecule are highly conserved, including the ankyrin repeats in
the N-terminal part of the molecule and the sequence around the phosphorylation
site. In addition, these isoforms all contain the four residue PP1c-binding motif
(Arg/Lys-Val/Ile-Xaa-Phe). MYPT has been detected in a variety of cells and thus
is not unique to smooth muscle. With phosphorylated myosin as substrate, the
phosphatase activity of PP1c is low and is enhanced on addition of MYPT. It is
assumed that MYPT functions as a target subunit and binds to both PP1c and
substrate. The N-terminal fragment of MYPT is responsible for the activation of
PP1c activity, but how much of the N-terminal sequence is required is not
established. An important point is that activation is not a general effect and is
specific for myosin. It is not known if other substrates may be targeted to MYPT.
There are two binding sites for PP1c on MYPT: a strong site in the N-terminal
segment (containing the 4-residue motif) and a weaker site in the ankyrin
repeats, possibly in repeats 5, 6 and 7. The location(s) of the myosin-binding
sites on MYPT is controversial, and binding of myosin, or light chain, to both N-
and C-terminal fragments has been reported. Regulation of myosin phosphatase
activity involves changes in subunit interactions, although molecular mechanisms
are not defined. There are basically two theories proposed for phosphatase
inhibition (i.e. as seen in the agonist-induced increase in Ca2+ sensitivity).
One hypothesis is that phosphorylation of Myosin light chain phosphatase MYPT (at
residue 654 or 695 of the gizzard MYPT isoforms or an equivalent residue)
inhibits the activity of the MP holoenzyme. The kinase involved is not
established, but may be an unidentified endogenous kinase or a RhoA-activated
kinase. The latter is an attractive possibility because there is convincing
evidence that RhoA plays a crucial role in the Ca(2+)-sensitizing process in
smooth muscle. A second idea involves arachidonic acid. This is released via
phospholipase A2 and could either interact directly with MYPT and cause
dissociation of the holoenzyme (thus effectively reducing the phosphatase
activity to that of the isolated catalytic subunit), or it could activate a
kinase that would phosphorylate MYPT and inhibit the phosphatase. It is possible
that MP activity may also be activated, for example, following increases in cAMP
and/or cGMP. Evidence in support of this is very limited and under in vivo
conditions the phosphorylation of MYPT by the respective kinases has not been
demonstrated. There is, however, a tentative hypothesis based on in vitro data
that phosphorylation of MYPT by PKA alters its cellular localization. This
involves a shuttle between the dephosphorylated membrane-bound and inhibited
state (at least towards P-myosin) to a phosphorylated cytosolic or cytoskeletal,
and active state. The pathway(s) discussed above originates at the cell membrane
and is carried via one or more messengers to the level of the contractile
apparatus where it is manifested by regulation of phosphatase activity. Various
components of the route have been identified, including RhoA and the atypical PKC
isoforms, but more remain to be discovered. It is possible that more than one
pathway, or cascade, is
PMID- 9635277
TI - Expression of lactate dehydrogenase, myosin heavy chain and myogenic regulatory
factor genes in rabbit embryonic muscle cell cultures.
AB - The expression of myogenic regulatory factors (MRFs), lactate dehydrogenase (LDH)
and myosin heavy chains (MyHC), as markers of myogenesis, metabolism and
contractility respectively, were investigated during differentiation of rabbit
embryonic muscle cells in primary culture. Myf5, MyoD and myogenin mRNAs were
abundantly expressed at day 1 of culture. The expression of Myf5 and MyoD mRNA
transcripts decreased sharply as myoblasts fused and differentiated into
myotubes, whilst myogenin mRNA was maintained throughout the duration of the
culture. In contrast, MRF4 mRNA was weakly expressed on day 1 of culture, its
expression increased slightly as myoblasts fused and reached a maximum level in 7
day-old cultures containing striated myofibres. The specific activity of LDH
increased linearly during myoblast proliferation and fusion. In 7-day-old
cultures, LDH-M mRNA (dominant in glycolytic muscles) and LDH-H mRNA (predominant
in perinatal and oxidative muscles) represented 38% and 62% of total LDH mRNA
respectively. At this stage, immunocytochemical staining with perinatal and adult
type MyHC antibodies showed that embryonic and perinatal MyHC isoforms were
expressed in all myotubes, while few of them were stained by type I MyHC
antibody. However, none of them expressed adult type II MyHC. The latter results
were further supported by RT-PCR analysis of adult-type MyHC mRNA which showed
that only the type I MyHC mRNA transcript was expressed. These data were in
agreement with those reported in vivo on perinatal rabbit muscles. They differed
from those obtained on cultured satellite cells isolated from adult rabbit fast
twitch or slow-twitch muscles which did not express embryonic MyHC, and instead
expressed fast- or slow-type MyHC according to their muscle origin. Taken
together, these results further suggest that myogenic mononucleated cells express
different properties in vitro according to their developmental origin as well as
properties related to those of the muscles from which they were isolated.
PMID- 9635279
TI - Improvement of the measurements on skinned muscle fibres by fixation of the fibre
ends with glutaraldehyde.
AB - Experiments with activated skinned muscle fibre segments are limited by the
structural and mechanical instability of the preparations. The present study
shows that fixation of the muscle fibre ends with glutaraldehyde significantly
improves the reliability of such experiments. We tested the effects of a specific
glutaraldehyde fixation technique on the structural stability and the mechanical
properties of skinned rat and rabbit skeletal muscle fibres in an approach where
the fibre segments are attached to the apparatus by gluing. Preparations with
fixed and unfixed ends were compared. During the first few minutes of maximal
activation, fibres with fixed and unfixed ends exhibited similar mechanical
properties to one another, suggesting that our fixation procedure selectively
impregnates the fibre ends without contaminating the remaining active fibre part.
During prolonged maximal activations (3-60 min), preparations with fixed ends
exhibited a better stability, both in the sarcomere length signal (detected by
laser diffraction) and in the unloaded shortening velocity. Thus, our technique
of muscle fibre end fixation caused a substantial improvement in the mechanical
measurements on skinned muscle preparations.
PMID- 9635278
TI - Effects of calcium and nucleotides on the structure of insect flight muscle thin
filaments.
AB - The structure of the insect flight muscle thin filament has been studied using a
Drosophila mutant (Ifm(2)2) which does not contain thick filaments. Thin
filaments that are biochemically identical to those of the wild type can be
isolated free from thick filament contamination. We show that isolated thin
filaments have different symmetries depending upon the calcium concentration.
While the filaments mainly contain 13 subunits in six turns of the 5.9 nm genetic
helix in the absence of calcium, 50% of the filaments have 28 subunits in 13
turns of the genetic helix at calcium concentrations equivalent to those present
during muscle contraction. We also show that the structure (mainly the helical
order) of the thin filaments depends on the nature of the nucleotide bound to the
actin monomers. Three-dimensional reconstructions of the thin filaments in the
presence and absence of calcium show that tropomyosin moves between two different
positions on the actin filament. However, in Drosophila the amplitude of the
movement as well as the disorder in the positions of the components (tropomyosin,
troponin complex) are larger than those generally observed in other species.
PMID- 9635280
TI - Acute and sustained effects of isometric and lengthening muscle contractions on
high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.
AB - Previous studies have shown that lengthening contractions, in contrast to
isometric contractions, readily result in sustained malfunctioning of the
exercised muscles. The present study was performed to investigate whether an
exercise period with many (240) lengthening contractions (LC) results in
alterations in muscle high-energy phosphates and inosine monophosphate (IMP)
content, different from muscles performing a few (60) lengthening or a few (60)
or many (240) isometric contractions (IC). Moreover, we sought for a possible
cause(s) of the inability to replenish muscle glycogen stores following LC. Rat
tibialis anterior muscles were subjected in vivo to either 60 or 240 LC or IC.
Structural muscle damage occurred only after 240 LC. The fact that tissue
glycogen levels declined to a similar extent during LC and IC suggests that the
energy demand was comparable during both types of exercise. Nevertheless, the
observation that on the one hand tissue stores of adenine nucleotides showed a
greater decline, and on the other hand the tissue content of IMP increased to a
significantly higher level after LC than after IC, clearly indicates that muscle
energy metabolism is more disturbed during LC than during IC. The high tissue
levels of IMP may contribute to impaired mechanical function as previously
observed in muscles subjected to LC. In contrast to 240 IC, 24 hours after 240
LC, tissue glycogen stores and high-energy phosphate levels were not restored to
control values. The present findings indicate that depressed glycogen synthase
activity and impaired activity of the mitochondrial marker enzyme cytochrome C
oxidase probably contribute to a continuous disturbance of energy metabolism in
the exercised muscles during the 24 hours following 240 LC.
PMID- 9635281
TI - Probing the coupling of Ca2+ and rigor activation of rabbit psoas myofibrillar
ATPase with ethylene glycol.
AB - We have exploited solvent perturbation to probe the coupling of Ca2+ and rigor
activation of the ATPase of myofibrils from rabbit psoas. Three techniques were
used: overall myofibrillar ATPases by the rapid-flow quench method; kinetics of
the interaction of ATP with myofibrils by fluorescence stopped-flow; and
myofibrillar shortening by optical microscopy. Because of its extensive use with
muscle systems, ranging from myosin subfragment-1 to muscle fibres, we chose 40%
ethylene glycol as the relaxing agent. At 4 degrees C, the glycol had little
effect on the myofibrillar ATPase at low [Ca2+], but at high [Ca2+] the activity
was reduced 50-fold, close to the level found under relaxing conditions, and
there was no shortening. However, the ATPase of chemically cross-linked
myofibrils (permanently activated even without Ca2+) was reduced only 3-4-fold.
The lesser reduction of the ATPase of permanently activated myofibrils was also
observed in single turnover experiments in which activation occurs by a few heads
in the rigor state activating the remaining heads. The addition of ADP, which
also promotes strong head-thin filament interactions, also activated the ATPase
but only in the presence of Ca2+. Further experiments revealed that in 40%
ethylene glycol, Ca2+ does initiate shortening but only with the aid of strong
interactions and at temperatures above 15 degrees C. This confirms that in the
organized and intact myofibril, Ca2+ and rigor activation are coupled, as
proposed previously for regulated actomyosin subfragment-1.
PMID- 9635283
TI - Involvement of the cytoskeleton in calcium-dependent stress relaxation of rat
aortic smooth muscle.
AB - Rat aortic smooth muscle exhibits a remarkable capacity for stress relaxation,
the release of tension following tissue stretch. Stress relaxation was markedly
enhanced in contracted aortic rings compared with unstimulated tissue. The
magnitude of stress relaxation in contracted aortic rings correlated well with
the passive tension imposed on the tissue by stretching, but showed little
relationship to changes in tissue length or to the level of tension developed in
response to agonist stimulation prior to stretch. The enhancement of stress
relaxation in precontracted tissue was not affected by intimal rubbing or
treatment with L-NAME. By comparison, the removal of extracellular calcium
markedly attenuated stress relaxation. In addition, the use of cytochalasin B to
block actin polymerization inhibited stress relaxation, whereas colchicine, a
drug used to cause microtubule disassembly, had no effect on the phenomenon. The
results indicate that the enhanced stress relaxation in contracted tissue is a
calcium-dependent process and is not due to passive tissue elastic properties. We
suggest that stress relaxation may not involve cross-bridge formation but could
be explained by the remodelling of a portion of the tension-bearing actin
cytoskeleton.
PMID- 9635282
TI - Troponin-T is a calcium-binding protein in insect muscle: in vivo
phosphorylation, muscle-specific isoforms and developmental profile in Drosophila
melanogaster.
AB - Two sets of muscle polypeptides showing calcium-binding capacity and intense
labelling in vivo with 32P were purified and characterized from Drosophila
melanogaster adult extracts. The polypeptides exhibit crossed immunoreactivity
and share similar biochemical properties such as those involved in purification.
They have been identified as isoforms of troponin-T (TnT) by sequence analysis of
a cDNA clone isolated from an embryonic library. The two sets of TnT polypeptides
correspond to the fibrillar and non-fibrillar muscle isoforms, respectively. The
non-fibrillar muscle isoforms separate into two bands which are differentially
expressed during development. Analysis of TnT isoforms in bee thoraces indicates
that the expression of the fibrillar muscle isoform correlates with the
acquisition of functional flight capability. In vivo labelling experiments reveal
that the two TnT sets are readily phosphorylated. The Drosophila TnTs show
calcium-binding properties by three different types of assays. Our results
suggest that this property could be specific to insect TnTs and may be related to
the long, extremely acidic polyglutamic carboxy-terminus present in these
polypeptides, which does not occur in non-arthropod TnTs.
PMID- 9635284
TI - Mechanical alterations in smooth muscle from mice lacking desmin.
AB - Mice with a null mutation introduced in the desmin gene were used to study the
mechanical role of intermediate filaments in smooth muscle cells. Vas deferens
(VD), urinary bladder (UB) and portal vein (PV) preparations were obtained from
adult animals lacking desmin (Des -/-) and from age- and weight-matched wild-type
animals (Des +/+). Active force per cross-sectional area was decreased in the
smooth muscle of the Des -/- compared with Des +/+ mice (VD to 42%; UB to 34%).
Quantitative gel electrophoresis suggests a marginally lower cellular content of
myosin, but the organization of the contractile apparatus appeared unchanged by
electron microscopy. A similar reduction in stress was measured in Des -/-
skinned fibres showing that altered activation mechanisms were not involved. The
results indicate that the reduced active force is caused by low intrinsic force
generation of the contractile filaments or subtle modifications in the coupling
between the contractile elements and the cytoskeleton. The relationship between
length and passive stress was less steep in the Des -/- samples and a second
length force curve after maximal extension revealed a loss of passive stress. The
maximal shortening velocity was reduced in Des -/- skinned VD and UB preparations
by approximately 25-40%. This was associated with an increased relative content
of the basic essential myosin light chain, suggesting that alterations in the
contractile system towards a slower, more economical muscle had occurred. PV
preparations showed no difference in mechanical properties in Des +/+ and Des -/-
animals, a result that was consistent with the predominance of vimentin instead
of desmin in this vascular tissue. In conclusion, the results show that, although
intermediate filaments in smooth muscle are not required for force generation or
maintenance of passive tension, they have a role in cellular transmission of both
active and passive force.
PMID- 9635285
TI - Evidence for distinct fast and slow myogenic cell lineages in human foetal
skeletal muscle.
AB - To analyse the myogenic cell lineages in human foetal skeletal muscle, muscle
cell cultures were prepared from different foetal stages of development. The in
vitro muscle cell phenotype was defined by staining the myotubes with antibodies
to fast and slow skeletal muscle type myosin heavy chains using immunoperoxidase
or double immunofluorescence procedures. The antibodies to fast skeletal muscle
myosin heavy chains stained nearly all myotubes dark in cell cultures prepared
from quadriceps muscles at 10-18 weeks of gestation. The antibodies to slow
skeletal muscle myosin heavy chains, in contrast, stained only 10-40% of the
myotubes very dark. The remaining myotubes were further subdivided into two
populations, one of which was unstained while the other stained with variable
intensity for slow myosin heavy chain. The slow myosin heavy chain staining was
not influenced by the nature of the substratum used to culture these cells,
although the growth of muscle cell cultures was greatly improved on matrigel
coated dishes. The presence of both slow and fast myosin heavy chains was
detected even when myotubes were grown on uncoated petri dishes. The myotube
diversity was further investigated by analysing the clonal populations of human
foetal skeletal muscle cells in vitro. When cultured at clonal densities, two
types of myogenic clones were identified by their differential staining with
antibodies to slow myosin heavy chain. As was the case with the high density
muscle cell cultures, virtually all myotubes in both groups of clones stained
with antibodies to fast myosin heavy chains. Antibodies to slow myosin heavy
chains stained nearly all myotubes dark in one group of myogenic clones, but only
a subset of the myotubes stained dark for slow myosin heavy chain in the second
group of clones. The proportion of slow myosin heavy chain positive myotubes in
this group varied in different clones. The myogenic diversity was thus apparent
in both high density and clonal human muscle cell cultures, and myogenic cells
retained their ability to modify their muscle cell phenotype.
PMID- 9635286
TI - The annual meeting on muscle contraction and cell motility. Tokyo, Japan, 6-8
January 1998.
PMID- 9635287
TI - Missing children found dead.
AB - Forensic evidence in child homicide cases is critical to determine sexual abuse.
Forensic evidence can help focus an investigation on a suspect through DNA
results. Of 210 missing children found deceased, 68% were homicides, 16% had
accidental causes, 12% were unknown, and 4% were suicides.
PMID- 9635288
TI - Forbidden love: sexual exploitation in the forensic milieu.
AB - Strategies must be developed within forensic psychiatric nursing practice that
deal with issues surrounding forbidden love before, during, and after they arise.
Unfortunately, nurses are generally ill prepared to deal with the sexual dilemmas
that can occur in clinical practice. Sexual dilemmas must be recognized as an
occupational hazard and not a professional taboo. Open acknowledgement that the
potential for abuse exists in all nurse-client relationships is the key to
avoiding the pitfalls that lead to sexual impropriety.
PMID- 9635289
TI - "How do you feel?" Self-reported health as an indicator of current physical and
mental health status.
AB - Self-reported health can serve as a reliable indicator of an individual's
physical health status and future morbidity and mortality. Although patients are
commonly asked "How do you feel?" they are rarely asked to rate their health on a
continuum of excellent to poor. This question can be helpful in ascertaining the
need for further assessment or referral.
PMID- 9635290
TI - Process-oriented critical pathways in inpatient psychiatry: our first year.
AB - The critical pathway methodology of assigning and timing staff interventions and
expected patient outcomes has developed worldwide recognition, but is less likely
to be used in psychiatry than in other medical fields. At St. Mary's in
Rochester, New York, an interdisciplinary team adapted the critical pathway
concept to meet the needs of an acute inpatient population with relative success.
Although staff education needs continue and plans to modify the pathway are in
progress, all staff feel that the critical pathway is a viable tool for enhancing
patient care and optimizing resources use. Benefits, obstacles, and suggestions
are discussed.
PMID- 9635291
TI - Caring in a managed care environment--a case study in teamwork.
AB - Level of care decisions in managed care require matching the patient's intensity
of symptoms with the appropriate placement in the least restrictive setting. In
planning appropriate treatment for a patient, the case manager at a managed care
organization (MCO) considers "Why now?," examining the patient's diagnosis, as
well as other pertinent factors, such as precipitant and the proximal cause for
the patient's request for help. Team efforts between the MCO clinicians and the
patient's treating clinicians improve the likelihood of patient/treatment
outcome.
PMID- 9635292
TI - Regulation of growth hormone receptor gene expression.
AB - Pituitary growth hormone (GH) is essential for postnatal growth in animals. GH
exerts its actions by direct effect on target organs and by stimulating the
production of insulin-like growth factor I (IGF-I). At the tissue level, the
pleiotropic actions of GH result from the interaction of GH with a specific cell
surface receptor, the GH receptor (GHR). The GHR belongs to the hematopoietic
receptor superfamily. The human GHR is the product of a single gene located on
chromosome 5p13.1-p12 and spans at least 87 kb. Transcripts from this gene are
characterized by the presence of disparate 5' untranslated exons. In the liver at
least eight different GHR 5' untranslated regions (UTRs) have been described.
This heterogeneity in the 5' UTR most likely results from the splicing of the
various exon 1 fragments to a common splice site located 11 bp upstream of the
initiating ATG. Heterogeneity in the 5' UTR sequences of the GHR transcripts
indicates that transcriptional control of the locus is complex. GHR gene
expression is minimal to absent in the fetus, with the postnatal increase in
expression in the liver being maximal during pregnancy. GHR gene expression is
also regulated by factors such as nutritional intake, GH, steroid hormones, and
diabetes mellitus. Available information about the molecular mechanisms
regulating expression of the GHR gene is discussed. Thus the GHR gene presents a
picture of multiple 5' untranslated exons under the control of multiple
promoters. The use of alternate promoters for initiation of transcription in
conjunction with differential splicing allows for exquisite regulation of gene
expression. This schema is appropriate for a protein that is essential to many of
the physiological processes that are crucial for the survival and well-being of
the organism.
PMID- 9635293
TI - Molecular analysis and prenatal diagnosis of human fumarase deficiency.
AB - Fumarase deficiency is a rare autosomal recessive disorder of the citric acid
cycle causing severe neurological impairment. The cDNA for both the rat and human
enzymes has been cloned previously and shown to encode a coding region of 1.46
kb. To scan for mutations in fumarase-deficient patients we amplified the coding
region of fumarase from fibroblast/lymphoblast cDNA employing the oligonucleotide
primers designed from the published human and rat cDNA sequence. We then directly
sequenced the polymerase chain reaction product. In seven unrelated patients, we
detected four missense mutations (A265T, D383V, F269C, K187R), a nonsense
mutation (W458X), a 3-bp AAA insertion that introduces an additional lysine
residue at codon 435, and a spontaneous new mutation resulting in a 74-bp
deletion (66del74). Seven at-risk pregnancies were monitored with one prenatal
diagnosis of fumarase deficiency by molecular analysis and favorable outcome of
the other pregnancies as predicted by enzyme assay of cultured fetal cells or
molecular analysis.
PMID- 9635294
TI - Molecular and biochemical basis of galactosemia.
AB - Galactosemia is a clinically heterogeneous autosomal recessive inborn error of
metabolism caused by deficiency of galactose-1-phosphate uridylyltransferase
(GALT). Despite the numerous point mutations identified in the GALT gene, the
prevalence of these mutations in different ethnic groups has not been studied.
Reports on genotype/phenotype correlation are not consistent due to the small
sample sizes studied and the lack of a sensitive enzyme assay. We applied
multiplex PCR/ASO dot blot analysis to screen 293 galactosemic patients for 17
known point mutations in exons 5, 6, and 10. Our data demonstrate that only 7 of
these mutations were detected in our patients, accounting for 65% of the GALT
mutant alleles. Although Q188R is the most common mutation in Caucasian and
Hispanic patients, the S135L mutation is most common in African-Americans.
Another mutation, F171S, was observed only among African-American patients. An
improved, sensitive, and accurate method was used to measure GALT activity in
patient's red blood cells. The results indicated that patients homozygous for
Q188R have no enzyme activity while those homozygous for S135L had residual
enzyme activity. Interestingly, both Q188R/S135L and S135L/F171S compound
heterozygotes demonstrated zero enzyme activity. Overall, 85% of Q188R compound
heterozygotes also did not have any enzyme activity, whereas the remaining Q188R
and the majority of S135L compound heterozygotes expressed variable amounts of
GALT activity. We speculate that heterodimeric subunit interaction plays an
important role in determining the overall enzymatic activity. Various genotypes
thus result in biochemical and clinical heterogeneity among the patients.
PMID- 9635295
TI - Alpha 1-antitrypsin nonsense mutation associated with a retained truncated
protein and reduced mRNA.
AB - alpha 1-Antitrypsin (alpha 1AT) provides the major protection in the lung against
neutrophil elastase-mediated proteolysis. Inheritance of alpha 1AT deficiency
alleles is associated with an increased risk of emphysema and liver disease.
alpha 1AT null alleles cause the total absence of serum alpha 1AT and represent
the ultimate in a continuum of alleles associated with alpha 1AT deficiency. The
molecular mechanisms responsible for absence of serum alpha 1AT include splicing
abnormalities, deletion of alpha 1AT coding exons, and premature stop codons. We
identified an Italian individual with asthma, emphysema, and a very low level of
serum alpha 1AT. DNA sequencing demonstrated the Mprocida deficiency allele and a
novel null allele, QOtrastevere (c654 G-->A, W194Z), a nonsense mutation near the
intron 2 (IVS2) splice acceptor site. To determine the molecular basis of
QOtrastevere and specifically to evaluate whether this nonsense mutation
interfered with mRNA processing by altered splicing, we used a Chinese hamster
ovary cell line permanently transfected with QOtrastevere or normal M alpha 1AT
with and without IVS2. Northern blot analysis demonstrated that the normal M
construct, with or without IVS2, expressed alpha 1AT mRNA of a similar size. The
nonsense mutation was associated with moderately reduced alpha 1AT mRNA
regardless of the presence or absence of IVS2. Reduction in alpha 1AT mRNA
regardless of the opportunity for splicing supports a translational-translocation
model as the cause of reduced alpha 1AT mRNA rather than the nuclear scanning
model. Pulse-chase studies followed by immunoprecipitation demonstrated an
endoplasmic reticulum-retained 31 kDa QOtrastevere alpha 1AT, which was rapidly
degraded. Although mRNA content was moderately reduced, retention and rapid
intracellular degradation of the truncated form are the major mechanisms for the
absence of secreted alpha 1AT.
PMID- 9635296
TI - Type 2 Gaucher disease with hydrops fetalis in an Ashkenazi Jewish family
resulting from a novel recombinant allele and a rare splice junction mutation in
the glucocerebrosidase locus.
AB - Gaucher disease, the deficiency of the lysosomal enzyme glucocerebrosidase (EC
3.2.1.45), is frequently encountered in the Ashkenazi Jewish population. Carrier
screening for Gaucher disease by enzyme analysis performed during a routine
pregnancy indicated that both Ashkenazi parents were carriers. Screening for four
common Gaucher mutations was subsequently performed on fetal and parental DNA.
None of the common Ashkenazi mutations were identified. However, when exons 9-11
were amplified and digested with NciI to detect the L444P mutation, it appeared
that the mother and the fetus had an unusual allele and that the expected
paternal allele was not present. When the fetal amniocytes were found to have
less than 2% of the normal glucocerebrosidase activity and a fetal sonogram
revealed hydrops fetalis, the pregnancy was terminated. The diagnosis of severe
type 2 Gaucher disease was confirmed at autopsy. Ultrastructural studies of
epidermis from the fetus revealed the characteristic disruption of lamellar
bilayers, diagnostic for type 2 Gaucher disease. In subsequent studies of the
fetal DNA, long-template polymerase chain reaction amplification revealed one
appropriately sized band (approximately 6.5 kb) and one smaller (approximately
5.2 kb) band. Sequencing of the approximately 5.2-kb fragment identified a novel
fusion allele resulting from recombination between the glucocerebrosidase gene
and its pseudogene beginning in intron 3. This fusion allele was inherited from
the father. The result was confirmed by Southern blot analysis using the enzyme
S8tII. Sequencing of the 6.5-kb fragment identified a previously described,
although rare, T-to-G splice junction mutation in intron 10 of the maternal
allele, which introduced an NciI site. The couple had a subsequent pregnancy
which was also found to be affected. This case study identifies a novel
recombinant allele and an unusual splice junction mutation, and demonstrates that
even in the Ashkenazi population, screening for common mutations may not
accurately identify the most severe forms of the disease.
PMID- 9635297
TI - Aminopeptidase N in sera of healthy subjects is a different N-terminal processed
derivative from the one obtained from maternal serum.
AB - A major aminopeptidase present in normal human serum was purified to homogeneity
as a 150-kDa molecular species. Western blotting confirmed the binding of an anti
aminopeptidase N antibody to the protein. The N-terminal amino acid sequence of
the enzyme was determined. The first 13 amino acids of the enzyme completely
matched amino acids 59-71 of the sequence predicted from the human intestinal
aminopeptidase N cDNA nucleotide sequence. As reported previously, aminopeptidase
N from maternal serum had 68 fewer amino acid residues at the N-terminus than the
enzyme obtained from detergent-solubilized membranes. The results indicate that
aminopeptidase N in normal serum is a different N-terminal processed derivative
from that obtained from maternal serum.
PMID- 9635298
TI - Identification of urokinase as a hyperoxia-inducible gene.
AB - Hyperoxia has deleterious effects on lung form and function; however, the
molecular events initiated by oxygen exposure remain unclear. We hypothesized
that macrophages function as important intermediaries in the protective response
of lung tissues after exposure to hyperoxia. This hypothesis was tested by
exposing cultured macrophages (RAW 264.7 cells) to hyperoxia for 24 h and then
applying the conditioned medium from these cells to cultured pulmonary epithelial
cells or to pulmonary microvascular endothelial cells. We observed that the
expression of manganese superoxide dismutase mRNA increased in both target cell
lines. Therefore, we next hypothesized that exposure of these macrophages to
hyperoxia results in a change in gene expression which could be detected by
differential display PCR (ddPCR). This hypothesis was tested by exposing RAW
264.7 cells to > or = 95% oxygen (or normoxia) for 24 h, harvesting RNA, and
performing ddPCR. A cDNA fragment upregulated by hyperoxia was identified and
reamplified. Verification of differential expression of mRNA was done by Northern
analysis. A mRNA which was reproducibly upregulated by hyperoxia, as well as by
lipopolysaccharide and interferon gamma, was identified. The differentially
expressed PCR product was cloned and sequenced, revealing a product with 99%
identity to mouse urokinase mRNA. We speculate that one function of pulmonary
macrophages following a hyperoxic exposure is to secrete urokinase.
PMID- 9635299
TI - [Neurosurgery and molecular biology: (series 4) molecular biology of
oncogenesis].
PMID- 9635300
TI - [Temporary arterial occlusion in aneurysm surgery].
PMID- 9635301
TI - [Visualization of venous system by volumegraph: navigation system of brain tumor
surgery].
PMID- 9635302
TI - [Differential diagnosis of hyponatremia following subarachnoid hemorrhage].
AB - Hyponatremia is a common complication after subarachnoid hemorrhage (SAH).
Although the mechanism of hyponatremia is still controversial, cerebral salt
wasting syndrome (CSNS) is currently regarded as being more responsible than the
syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The aim of
our study was to assess the plasma volume status of a patient with hyponatremia
following subarachnoid hemorrhage. In doing this it may be possible to indirectly
differentiate its pathogenesis. Fifty patients with SAH were studied. Twenty
patients demonstrated hyponatremia (serum sodium < 135 mEq/L) during day 7 to 13
after subarachnoid hemorrhage. Patients with hyponatremia were categorized on the
basis of their daily body weight, and central venous pressure. Group A consisted
of patients with hypovolemia (16 patients), with the onset time of hyponatremia
being day 7 to 9. Group B included those with hypervolemia (4 patients);
hyponatremia was observed during day 10 to 11 and was corrected in all patients
within 72 hours after induction of fluid restriction. Our findings suggest that
hyponatremia following subarachnoid hemorrhage usually occurs due to CSWS,
although SIADH remains as a minor pathogenesis. We conclude that the combination
of daily body weight and CVP measurements is a simple and practical method to
distinguish promptly SIADH from CSWS.
PMID- 9635303
TI - [Japan Coma Scale as a grading scale of subarachnoid hemorrhage: a way to
determine the scale].
AB - BACKGROUND: The grading scale for subarachnoid hemorrhage (SAH) with inter-grade
outcome differences is essential for evaluating the effectiveness of newly
developed therapeutic modalities. Although Hunt's grade and WFNS scale have been
widely used, these grading scales do not meet this requirement. We previously
proposed a revised WFNS scale based solely on the Glasgow Coma Scale (GCS) that
has intergrade outcome differences of high-level significance. The Japan Coma
Scale (JCS) has been long and widely used in Japan. The purpose of this study is
to show whether it is possible to determine a reasonable SAH grading scale based
on the JCS and to show a way to determine an SAH grading scale. PATIENTS AND
METHODS: We retrospectively analyzed 1398 consecutive cases of aneurysmal SAH
operated on within Day 7 of the latest onset. The preoperative JCS and GCS were
evaluated just before the surgery and the Glasgow Outcome Scale (GOS), analyzed
with numerical transformation (1 = dead to 5 = good recovery), was estimated at 6
months after the onset. All 510 possible combinations of scores of JCS were
statistically tested under the following 2 assumptions; (1) JCS = 0 and JCS = 100
fall into a single independent grade. (2) No other single JCS score should fall
into a single grade. RESULTS: The outcome differences between JCS 0 and 1, and
100 and 200 are significant. The outcome difference between JCS 30 and 100 is
relatively higher than any other set of 2 scores of JCS. Only 5 combinations are
practical among the candidates to be analyzed. Out of 510 combinations, the
following combination shows the highest inter-grade outcome differences; I (JCS =
0, n = 375, mean GOS = 4.78) II (JCS = 1, 2; n = 310; mean GOS = 4.47) III (JCS =
3-30; n = 476; mean GOS = 3.96) IV (JCS = 100; n = 96; mean GOS = 3.10) V (JCS =
200, 300; n = 141; mean GOS = 2.33). In JCS, the mean outcome of JCS = 3 is worse
than those of JCS = 10, 20, and 30. The outcome difference between JCS 0 and 1 is
only significant in patients over 60 years old. CONCLUSION: Taking all the 510
possible combinations of JCS into consideration, we obtained a reasonable
combination containing 5 grades. Although this grading scale showed good inter
grade outcome differences, JCS is not preferable to GCS as a consciousness
evaluation system in the acute phase of SAH. We emphasize the importance of this
way to determine a grading scale with a combinatorial approach, which can be
applicable for re-evaluating the grading scales in the future.
PMID- 9635304
TI - [Discrepancy between surgeon's binocular parallax perception and manipulation in
the neurosurgical operation].
AB - The application of virtual reality (VR) to the neurosurgical field has been
increasing recently, however, the relation between the surgeon and the VR
environment is rarely studied. We examined the trajectory of a surgical
instrument during manipulation of a virtual object using a video-see-through
microscope and a neurosurgical navigator (CANS Navigator) to find better surgeon
microscope interface. A resin cylindrical phantom was produced representing the
surgical field, which included two 3 dimensionally arranged small spheres and a
virtual 'gate'. The phantom was fixed and set under the microscope with a skull
clamp mimicking conditions in an ordinary craniotomy. Firstly, the binocular
parallax perception under microscope was examined. Experienced and inexperienced
neurosurgeons were asked to learn the position of the virtual 'gate' for 3
minutes. Then, after 5 minutes to point with the navigator probe (suction tube),
under various conditions; under the naked eyes, under the microscope, under the
navigator without observing the phantom, and under the microscope with picture in
picture (PIP) display of the navigational image. The positions of the suction
tube were recorded at real time into the navigator for later analysis. Secondly,
the task performance in this VR environment was studied by analyzing the
trajectory of the suction tube from one sphere to the other sphere passing the
virtual 'gate' under various conditions. A significant difference in pointing
precision between experienced and inexperienced neurosurgeons was able to be
observed only under microscope. This difference was mainly derived from
overestimation of the depth of the virtual 'gate' by the inexperienced
neurosurgeons. Among the above conditions, pointing under the microscope with PIP
was able to be performed the most precisely and the most promptly. This study
disclosed the presence of stereoscopic distortion in the microscope. The PIP
display of the navigational image in the microscopic view remarkably improved the
task performance, which could be accounted for by the correction of the somewhat
distorted binocular parallax perception under the neurosurgical microscope by the
provision of another visual key.
PMID- 9635305
TI - [A case of bilateral infraoptic course of ACA associated with multiple cerebral
artery aneurysms].
AB - Infraoptic course of anterior cerebral artery (ACA) is a rare cerebral vascular
anomaly frequently associated with intracranial aneurysm. A 58-year-old woman
suffered, subarachnoid hemorrhage due to aneurysmal rupture. Carotid angiography
revealed multiple aneurysms and bilateral infraoptic course of ACA. Usual A1
segments were not visualized on both sides. These findings were also confirmed by
craniotomy. Only 46 cases have been reported including ours. In this paper, we
reviewed previously reported cases and the cause of aneurysm formation was
discussed.
PMID- 9635306
TI - [Usefulness of positron emission tomography to STA-MCA anastomosis for the case
with cerebral infarction].
AB - The ischemic area surrounding the cerebral infarction in the eloquent area was
salvaged by STA-MCA bypass surgery. Both the misery perfusion area evaluated by
positron emission tomography (PET) using the [15O] gas inhalation steady-state
method and clinical symptoms improved within a year after surgery. To confirm the
ischemic area and select the suitable recipient artery was important for
successful bypass surgery, because only an artery covering the ischemic area is
expected to have low resistance. In this case a large ischemic area with
disturbed, vasodilatation by Diamox was detected on the SPECT. However, PET
clearly exposed the localized misery perfusion area in the overestimated ischemic
area by SPECT. We describe our experience and discuss the technique and efficacy
of PET for STA-MCA anastomosis surgery.
PMID- 9635307
TI - [A new operative technique of posttraumatic syringomyelia: thecoperitoneal
shunt].
AB - The authors report a successful case of operative treatment for a patient with a
traumatic syringomyelia. A 33-year-old male presented with arm pain and right
sided sensory loss due to posttraumatic syringomyelia. Magnetic resonance image
showed syringomyelia from the upper cervical cord to the lower thoracic cord.
Based on the hypothesis of Ball and Dayan, and Williams, a thecoperitoneal shunt
operation was performed. The proximal shunt catheter was placed in the
subarachnoid space rostral to the injury level and the distal shunt catheter was
introduced percutaneously into the peritoneum. Postoperative radiological studies
showed improvement and progressive clinical deterioration stopped. The advantages
of this surgery are that it is less invasive to the spinal cord, and that there
is a lower shunt malfunction rate because of the use of a D-L catheter which
develops less shunt obstruction. Furthermore, we were able to evaluate shunt flow
from the valve. In spite of multicystic syrinx, we were easily able to determine
the placement of the shunt catheter for this operation. For these reasons, the
thecoperitoneal shunt can be placed before further expansion of the syrinx. We
think that this method is safer for patients with incomplete cord injury than S-P
shunt or S-S shunt.
PMID- 9635308
TI - Prevention of bacterial endocarditis: a statement [of confusion] for the
[pediatric] dental professional.
PMID- 9635309
TI - Treating Medicaid children.
PMID- 9635310
TI - Detection of fungal organisms in saliva from HIV-infected children: a preliminary
cytologic analysis.
AB - PURPOSE: Fungal infections in HIV-infected individuals are associated with
advancement of disease. In pediatric HIV infection, symptomatic children have a
significantly higher incidence of clinical candidiasis and persistent drug
resistant candidiasis than do asymptomatic HIV-infected children. The purpose of
this preliminary cytologic study was to determine the prevalence of fungal
organisms in whole unstimulated saliva from children with vertically acquired HIV
infection. METHODS: The subjects included 27 HIV-infected and 11 HIV-exposed, but
uninfected, children. Whole unstimulated saliva was obtained for cytologic
evaluation (hematoxylin and eosin, silver stains) with selected samples evaluated
by electron microscopy. RESULTS: Yeast and hyphae were identified cytologically
in 19% of HIV-infected (22% symptomatic HIV-infected, 11% asymptomatic HIV
infected) and 9% of HIV-exposed, but uninfected, children. Fungal organisms were
found more frequently in HIV-infected with moderate (18%) and severe (27%)
suppression. Fungi were more frequent with antiretroviral therapy (22%) vs no
antiretroviral therapy (0%) and no antifungal therapy (20%) vs. antifungal
therapy (7%). Yeast and hyphal fungal forms are more prevalent in symptomatic HIV
infection with moderate and severe suppression, and those receiving
antiretroviral agents, but no antifungal medications. CONCLUSION: Fungal
organisms in the saliva may reflect oral carriage or mucosal colonization, which
may influence the development of clinically significant candidiasis in these
immunocompromised children.
PMID- 9635311
TI - Gingival status of HIV+ children and the correlation with caries incidence and
immunologic profile.
AB - PURPOSE: The aim of this study was to determine gingival health and caries levels
in HIV-infected children. METHODS: The modified gingival index (GI) of 43 HIV+
children of both sexes, aged between 2 and 12 years, was measured and correlated
with the DMFT/dmf. The children's immunodeficiency level was also established by
means of the CD4:CD8 ratio. Pearson's product-moment correlation co-efficient and
the Mann-Whitney U test were used. RESULTS: The GI was significantly related to
the DMFT/dmf. The children with a GI = 0 presented significantly more DMFT/dmf
than the children with a GI > or = 0.1, but there were no significant differences
between the GIs of caries-free children and those with DMFT/dmf > or = 1. The
children who presented a CD4:CD8 > or = 0.5 ratio presented less DMFT/dmf
compared with children who presented a CD4:CD8 < 0.5 ratio. The children who
presented a CD4:CD8 < 0.5 ratio presented a statistically significant correlation
between their GI and their DMFT/dmf, unlike children who presented a CD4:CD8 > or
= 0.5 ratio. Children with a CD4:CD8 < 0.5 who showed a greater DMFT/dmf index
also showed greater gingival inflammation. CONCLUSIONS: In this study, children
with greater caries experience showed more gingival inflammation. In addition, a
greater immunological deficiency might indicate a greater caries experience in
children.
PMID- 9635312
TI - Microleakage of sealants after conventional, bur, and air-abrasion preparation of
pits and fissures.
AB - PURPOSE: The aim of this study was to compare the microleakage of unfilled and
filled sealants after conventional, bur, and air-abrasion tooth preparation.
METHODS: Seventy-two extracted molars were randomly divided into three groups. In
group 1, 24 teeth were prepared by pumicing and acid etching with 37% phosphoric
acid. In group 2, 24 teeth were prepared with a 1/4-round bur in a low-speed
handpiece and then acid etched. In group 3, 24 teeth were prepared by high-speed
(160 PSI) microabrasion using 50 mu alpha alumina particles in a KCP 2000
machine. In each group, 12 teeth were sealed with a filled sealant and 12 teeth
with an unfilled sealant. All the teeth were stored in artificial saliva for 7
days and thermocycled for 2000 cycles. Teeth were then sealed apically and coated
with nail varnish 1 mm from the margins and stained in 1% methylene blue for 24
h. Each tooth was sectioned in three locations and ranked (0-3) for microleakage.
RESULTS: There were 216 sections and 66% showed no leakage. CONCLUSIONS: Chi
square statistical analysis of the data led to the following conclusions: 1)
superior results were obtained when the tooth surfaces were prepared by a bur, 2)
conventionally and KCP 2000-prepared tooth surfaces yielded similar results, and
3) the unfilled sealant was superior to the filled sealant.
PMID- 9635313
TI - Effects of formocresol alone vs. formocresol with eugenol on macrophage adhesion
to plastic surfaces.
AB - PURPOSE: The purpose of this study was to compare the in-vitro effects of a
European-based formocresol formulation that incorporates eugenol with formocresol
alone on the adhesion of macrophages to plastic surfaces. METHODS: Macrophages
were obtained from Wistar rats. The adherence capacity of macrophages to a
plastic surface was determined. Assays were carried out in Eppendorf tubes
incubated for 15 min at 37 degrees C in a humidified atmosphere of 5% CO2. The
adherence index was calculated. RESULTS: Results showed that both
formocresol/eugenol and formocresol alone significantly decreased the adherence
index of macrophages. The formocresol formulation that incorporated eugenol was
more potent in inhibiting macrophage adhesion than formocresol alone.
CONCLUSIONS: Taking into account that adherence to a substrate is the first step
in the phagocytic process of macrophages and in antigen presentation, both
formocresol formulations could inhibit macrophage function and modulate immune
and inflammatory responses in dental pulp and periapical tissues.
PMID- 9635314
TI - The impact of WIC dental screenings and referrals on utilization of dental
services among low-income children.
AB - PURPOSE: This cross-sectional study examined whether referrals from nondental
health professionals impacted utilization of dental services by low-income
populations. METHODS: A sample of 309 mothers enrolled in the Women, Infant, and
Children (WIC) clinic in Jackson County, Missouri, completed a self-administered,
32-item questionnaire to assess the mother and child's oral health behavior and
past use of dental services. Dental utilization, the primary dependent variable,
was defined as whether or not the child had ever been to a dentist. RESULTS:
Findings showed 27% of the children in the sample had been referred for dental
care. Bivariate analysis indicated that a dental referral, age of the child, age
of the mother, mother's perceived dental need for the child, household size,
number of children in the household, and dental insurance for the child were
associated with a child having a dental visit. Logistic regression, however,
indicated that only age was significantly related to utilization. CONCLUSION: The
results showed a strong effect of increasing age being related to dental
utilization, while additional research is needed to clarify the importance of WIC
referrals.
PMID- 9635315
TI - A study of small superficial capillary hemangiomas on the lips in children.
AB - PURPOSE: This study describes 77 small vascular lesions on the lips of 74
children and adolescents. RESULTS: Of the 77 lesions, 70% were on the lower lip
and 30% on the upper. The diameter range was 0.5-5.0 mm (mean 1.4 mm). On both
lips the lesions were in the vermilion zone, close to the border with the skin.
The surface of the lesions was smooth and slightly raised, and varied in color
from red (49%) through bluish red (45%) to purple (6%). The borders were well
defined in most cases. The histology of the lesions was consistent with capillary
hemangioma. Small superficial capillary hemangiomas (SSCH) in this study behaved
differently from most hemangiomas and vascular malformations in that they did not
increase in size, and were persistent in the age group in which most hemangiomas
are reported to involute or disappear. The gender distribution of SSCH also
differed from the female predominance in hemangioma. SSCH is a solitary benign
lesion on the lips of children and adolescents, which has not been separately
classified before. CONCLUSIONS: Based on the differences from hemangioma in
gender distribution, size, border definition, and growth characteristics, it is
suggested that SSCH be classified as a variant or a subgroup of hemangioma.
PMID- 9635316
TI - Delayed tooth eruption in congenital hypertrichosis lanuginosa.
PMID- 9635317
TI - Multiple pre-eruptive intracoronal radiolucent lesions in the permanent
dentition: case report.
PMID- 9635318
TI - Odontodysplasia: report of two cases.
PMID- 9635319
TI - Pycnodysostosis: orofacial manifestations in two pediatric patients.
PMID- 9635320
TI - Otodental syndrome: three familial case reports.
PMID- 9635321
TI - How outcomes and evidence can strengthen the role of the pediatric dentist.
PMID- 9635322
TI - Oral health outcomes and evidence-based care.
PMID- 9635323
TI - Outcomes and the scientific basis of clinical care.
PMID- 9635324
TI - Pediatric dental treatment outcomes: the importance of multiple perspectives.
PMID- 9635325
TI - 1997 C. H. McCloy Research Lecture: Knowledge is more than we can talk about:
implicit learning in motor skill acquisition.
AB - This article discusses the acquisition of knowledge about environmental
regulatory features that guide the selection and execution of movements involved
in performing open motor skills. First, empirical evidence related to the visual
search characteristics of skilled and novice performers is considered to
demonstrate that learning environmental regulatory features is an important part
of performing an open motor skill. Then, the hypothesis is proposed and discussed
that environmental regulatory features can, and probably should, be learned
implicitly, which means the features can be learned and used, even though the
learner is not consciously aware of the specific characteristics of those
features. This article also discusses laboratory-based experiments that provide
evidence supporting this hypothesis and presents implications for developing
instructional strategies and practice conditions.
PMID- 9635326
TI - Visual search strategy, selective attention, and expertise in soccer.
AB - This research examined the relationship between visual search strategy, selective
attention, and expertise in soccer. Experienced (n = 12) and less experienced (n
= 12) soccer players moved in response to filmed offensive sequences. Experiment
1 examined differences in search strategy between the two groups, using an eye
movement registration system. Experienced players demonstrated superior
anticipation in 3-on-3 and 1-on-1 soccer simulations. There were no differences
in search strategy in 3-on-3 situations. In 1-on-1 simulations, the experienced
players had a higher search rate, involving more fixations of shorter duration,
and fixated for longer on the hip region, indicating that this area was important
in anticipating an opponent's movements. Experiment 2 examined the relationship
between visual fixation and selective attention, using a spatial occlusion
approach. In 3-on-3 situations, masking information "pick up" from areas other
than the ball or ball passer had a more detrimental effect on the experienced
players' performances, suggesting differences in selective attention. In 1-on-1
situations, occluding an oncoming dribbler's head and shoulders, hips, or lower
leg and ball region did not affect the experienced players' performances more
than the less experienced group. The disparities in search strategy observed in
Experiment 1 did not directly relate to differences in information extraction.
Experiment 3 used concurrent verbal reports to indicate where participants
extracted information from while viewing 3-on-3 sequences. Experienced players
spent less time attending to the ball or ball passer and more time on other areas
of the display. Findings highlight the advantages of integrating eye movements
with more direct measures of selective attention.
PMID- 9635327
TI - The effect of nonregulatory stimuli on the triple jump approach run.
AB - The purpose of this experiment was to examine the approach run of the triple
jump. Specifically, we examined the effect of nonregulatory stimuli (Gentile,
1972) on two different ability levels in performing the triple jump approach run.
These nonregulatory constraints (situational factors such as those seen in actual
competition) were employed in three jumping conditions: Control (to obtain
baseline performance measures), Distance (where participants attempted to obtain
as great a jump as possible), and Accuracy (participants attempted to be as
accurate as possible on takeoff without sacrificing distance). The results showed
that the footfall position variability for all conditions was similar to those
previously reported for the long jump approach run. However, in compliance with
the nonregulatory constraints, participants altered other performance parameters
in executing the approach run. The situational factors created changes that
revealed themselves in foot placement on the takeoff board at the end of the
approach run (foot position constant error and number of fouls increased for the
Distance condition) and decreased horizontal velocity at takeoff in the Accuracy
condition. Changes in performance parameters were related to the context in which
the skill was performed and may further reflect changes made by jumpers in the
course, such as a visual-motor task in competition. We suggest that the
characteristics of the approach run may not be fully revealed by the pattern of
footfall variability only, as has been suggested in previous work (e.g., Lee,
Lishman, & Thomson, 1982), but that the situation under which the jump is
performed may have a significant effect on the performance parameters that emerge
in executing this type of motor skill.
PMID- 9635328
TI - Motor performance and motor learning as a function of age and fitness.
AB - Past studies have shown that electroencephalographic alpha activity increases as
people learn to perform a novel motor task. Additionally, it has been suggested
that motor performance and learning decline as people age beyond 60 years, and it
has been hypothesized that physical fitness may attenuate this decline through
its impact on the cerebral environment. This study was designed to replicate past
research by assessing changes in alpha activity as a function of learning and to
extend past research by examining differences in motor performance, motor
learning, and alpha activity as a function of age and fitness. VO2max was
assessed in 41 older (ages 60-80 years) and 42 younger (ages 20-30 years)
participants. Participants were randomly assigned to experimental or control
conditions, which differed in the amount of practice received. Participants
performed trials on the mirror star trace on both an acquisition and a retention
day. Results indicated that younger participants performed better and had greater
learning than older participants. Fitness was not found to impact either
performance or learning. Participants in the experimental group improved more
than those in the control group and maintained this difference at retention,
which suggests that learning occurred. Associated with these improvements in
performance capabilities was an increase in alpha power.
PMID- 9635329
TI - The development of in-service teachers' knowledge of a constructivist approach to
physical education: teaching beyond activities.
AB - The purpose of this paper is to describe three aspects of learning a movement
approach that were salient and initially problematic for 1 experienced teacher, 2
early career teachers, and 1 student teacher. A constructivist perspective was
the theoretical base. Across 3 years, the researcher conducted 11 weeks of
observations, 15 formal interviews, 3 group interviews, and daily informal
interviews. Three problematic aspects were: (1) knowing to what extent they
should give information and tell children what to do when teaching less
structured content, (2) knowing the whole of the approach and how components
connected, and (3) knowing content (i.e., pedagogical content knowledge) in
enough depth and detail. Knowledge development was facilitated by more
experienced teachers, experience, and a set of key ideas.
PMID- 9635330
TI - Parental beliefs and children's moderate-to-vigorous physical activity.
AB - The present study was guided by the Family Influence Model to examine the role of
parental beliefs in their children's moderate-to-vigorous physical activity
(MVPA). The specific purposes were to (1) examine the nature of a parental belief
system that may be relevant to children's MVPA participation, (2) determine if
parental beliefs regarding their children's MVPA are gender related, (3) examine
the relationship between parents' exercise behavior and children's MVPA
participation, and (4) investigate the strength of the relationship between
parental beliefs and children's self-reported MVPA. The participants for this
study included 81 children (26 girls and 55 boys) between the ages of 11 and 15
years and their parents (n = 142). Significant findings were: (1) descriptive
evidence of a parental belief system for children's MVPA existed, (2) mothers and
fathers differed in their MVPA-related beliefs for their child, (3) no
relationship was found between parents' exercise behavior and children's MVPA
participation, and (4) parental beliefs relating to their children, especially
perceptions of competence and a task orientation, were significantly related to
the amount of children's MVPA participation. These findings support the basic
tenets of the Family Influence Model and suggest that parental beliefs should be
taken into consideration to better understand the psychosocial process underlying
children's participation in fitness-oriented physical activity.
PMID- 9635331
TI - The relationship between competitive anxiety, achievement goals, and motivational
climates.
AB - The purpose of this study was to examine the relationships of achievement goal
orientations and perceived motivational climate to perceptions of the intensity
and direction of competitive state anxiety in a sample of university athletes
representing various team sports. Although some studies have demonstrated that
task orientation and mastery climate are associated with adaptive emotional
patterns and ego orientation and performance climate are linked to less adaptive
emotions, others have not verified these findings. In the present study,
structural equation modeling was used to test these links. The results showed
that perceptions of a performance climate were associated with ego orientation,
whereas perceptions of a mastery climate were linked to task orientation.
Furthermore, no significant links were found between task orientation and
direction of competitive anxiety, while it was shown that the impact of ego
orientation on the intensity and direction of cognitive and somatic anxiety was
exerted through self-confidence. No significant direct links were found between
motivational climates and competitive anxiety, thus implying that motivational
climates may have an indirect impact on affective responses through the different
goal orientations. The findings of the present study are discussed along with
suggestions for examining situational and individual difference variables that
may explain the relationships between intensity and direction of competitive
anxiety and achievement goals and motivational climates.
PMID- 9635332
TI - Gender differences in preferences for coaching as an occupation: the role of self
efficacy, valence, and perceived barriers.
AB - This study investigated gender differences in the role of self-efficacy,
occupational valence, valence of coaching, and perceived barriers in preference
to coach at the high school, 2-year college, Division III, Division II, and
Division I levels. The participants, 191 Big Ten university basketball players
(94 men, 97 women), responded to a specially constructed instrument. The genders
did not differ in their coaching self-efficacy, preferred occupational valence,
and perceived barriers. Relative to men, women perceived greater valence in
coaching (p < .001). Women with a female coach perceived greater valence in
coaching (p < .05) and expressed less concern with perceived discrimination (p <
.05) than those with a male coach. Perceived self-efficacy and preferred
occupational valence were differentially related to the desire to coach at
various levels. Working Hours most negatively affected the desire to coach at
every level (R > .20).
PMID- 9635333
TI - Nasal strips and mouthpieces do not affect power output during anaerobic
exercise.
PMID- 9635334
TI - A modified version of the Rockport Fitness Walking Test for college men and
women.
PMID- 9635335
TI - Children's age moderates the effect of practice variability: a quantitative
review.
PMID- 9635336
TI - Acute effects of ambient ozone on asthmatic, wheezy, and healthy children.
AB - Southern California children (10 to 12 years old) participated in a two-season
study to assess the potential acute respiratory effects of ambient ozone (O3).
Asthmatic (n = 49), wheezy (n = 53), and healthy (n = 93) children completed a
four-day (Friday through Monday) study protocol, once in spring and again in
summer, that included the use of daily activity and symptom diaries, heart rate
recording devices, personal O3 samplers, and maximal effort spirometry several
times per day. Data from regional monitoring stations were used to establish
ambient hourly O3 concentrations. Analyses revealed that the children spent more
time outdoors and were more physically active in the spring. Girls spent less
time outdoors and were less physically active than boys. Personal O3 samplers
correlated poorly with, and generally gave lower readings than, outdoor ambient
monitors. Higher personal O3 exposures were associated generally with increased
inhaler use, more outdoor time, and more physical activity. Children with asthma
spent more time outdoors and were more active in the spring on high-O3 days
(measured by personal sampler), and had the most trouble breathing, the most
wheezing, and the most inhaler use on these days. Activity pattern data suggested
that children with asthma protected themselves by being less physically active
outdoors during the summer on high-O3 days. Wheezy children had the most trouble
breathing during the summer on low-O3 days (measured by personal sampler).
Observed relationships between O3 and pulmonary function were erratic and
difficult to reconcile with existing knowledge about the acute respiratory
effects of air pollution. We conclude that although asthmatic and wheezy children
behave differently from their healthy peers with regard to symptoms and patterns
of activity when challenged by ambient ozone, the nature of these changes remains
inconsistent and ill-defined.
PMID- 9635337
TI - New report and pilot studies on Chlamydia.
PMID- 9635338
TI - Escherichia coli O157 in Somerset.
PMID- 9635339
TI - Rise in falciparum malaria imported from east Africa.
PMID- 9635340
TI - Hepatitis C virus infection in children.
PMID- 9635341
TI - Protecting health care workers against bloodborne viruses.
PMID- 9635342
TI - Enhanced surveillance of meningococcal disease in five English regions: first
quarter 1998.
PMID- 9635343
TI - Outbreak of Vero cytotoxin producing Escherichia coli O157 infection in Dorset.
PMID- 9635344
TI - AIDS and HIV infection in the United Kingdom: monthly report.
PMID- 9635345
TI - The future belongs to those who plan for it.
PMID- 9635346
TI - The use of pure follicle stimulating hormone during the luteal phase to increase
success of ovulation induction in poor responders: a pilot study.
PMID- 9635347
TI - Medical practice evaluation: adding a physician assistant.
PMID- 9635348
TI - Yet another suggestion to improve quality of care.
PMID- 9635349
TI - [The tendency of antibiotic therapy in dental and oral surgical practice].
AB - The large number of dental inflammations can be explained by the bad general
dental condition in Hungary. Antibiotics have been used more extensively here
then in several other countries. The recently introduced antibiotics are
preserving the beneficial effects of the older ones with less side effects. The
oral flora and their resistance to antibiotics are very different in certain
countries. Therefore the professional protocols of the stomatological
inflammations followed by certain countries cannot be applied directly in other
countries. The changing resistance and the appearance of the new antibiotics make
necessary the general evaluation of different antibiotics from time to time. The
patients, the doctors and the society has the same interest: to get or provide
more and more fast, safe and effective treatment. But to achieve this objective
the dentists have to reevaluate their treatment habits accordingly.
PMID- 9635350
TI - [Sealing effectiveness of root canal fillings pretreated with Gluma Dentin Bond].
AB - The root canals of 41 extracted human teeth with single canal were shaped using
hand instruments. The canal walls of test roots [22] were pretreated with Gluma
resin. All of the canals were filled using the same method. The sealing ability
of root canal fillings was evaluated by dye penetration test and the morphology
of canal walls was observed by SEM. In the experimental group the dentin bond
covered the canal walls completely and the entrances of dentin tubules were
obturated. The dentin bond can be observed in the dentinal tubules as well. The
mean value of dye penetration was 0.53 mm for the control group and 0.37 mm for
the test group. The Gluma pretreatment of root canals increased the sealing
ability of AH 26, however, the difference was statistically not significant.
PMID- 9635351
TI - [Extensive intraoral cicatrization treated by microsurgery].
AB - Extensive intra-oral burns are very rare injuries. The microstomia resulting from
the advanced cicatrization of the mucosa makes it difficult for the patient to
eat and impossible to take care of his teeth. The traditional operation for
widening the oral orifice was not sufficient because of the extensive scarring of
the bucca. In the first operation the authors substituted the mucosa of the lip
and the bucca of one side with splitted jejunum. Because of the advancing
scarring another operation was performed and the mucosa of the other side of the
bucca and the angle of mouth was substituted with a forearm graft.
PMID- 9635352
TI - The types of neurons of the somatic oculomotor nucleus in the European bison.
Nissl and Golgi studies.
AB - The neuronal structure of the somatic oculomotor nucleus (SON) was studied on the
basis of Nissl and Golgi preparations, obtained from mesencephalons of 4 European
bisons. We distinguished four types of neurons in the investigated nucleus: 1.
The large multipolar nerve cells with 5-8 thick dendritic trunks and a thin axon
which emerges directly from the soma. These are the most numerous neurons in the
SON. 2. The small multipolar neurons. These cells have 4-6 thick dendritic
trunks. An axon arises mostly from initial segment of one of the dendrites. This
type represents about 8% neurons of SON. 3. The triangular neurons. From
perikaryon 3 thick dendritic trunks emerge. A thin axon arises directly from the
cell body. These cells make about 10% neurons of SON. 4. The pear-shaped cells
which have 1 or 2 dendritic trunks concentrate at one pole of the neurons. In the
SON there are about 2% pear-shaped cells. Their features correspond to the
features attributed by many authors to the interneurons.
PMID- 9635353
TI - Morphology of brain stem lesion and bera findings after 60Co irradiation.
AB - Ionizing rays, utilized in radiological diagnostics and oncological therapy
affect the central nervous system and may injure auditory pathways and cause
hearing disturbances which vary in intensity. On the basis of a stereotactic
atlas of the brain of a guinea pig, the trapezoid and geniculate bodies were
identified in the skull X-ray pictures. The irradiated region was found to have
10 x 6 x 5 mm in dimensions and to be situated at the depth of 11 mm away from
the animals occiput. After introductory recording of the potentials obtained from
the brain stems (BERA), the stems of 60 guinea pigs were irradiated in the groups
with the doses of 5, 10, 20 Gy. The hearing potentials from the brain stems were
recorded on the 1st, 4th, 10th, 21st and 84th day after irradiation. The findings
of measurements of hearing potentials were compared with the morphologic picture
of the brain stems in the examined animals.
PMID- 9635354
TI - Mandible measurements in aspect of some muscles attachment.
AB - The paper deals with a part of anatomical research in aspect of clinical
evaluation of lowering mandible muscles attachments (mylohyoid m, digastric m,
geniohyoid m.) and genioglossus muscle. The research was conducted on 183 adult
males and 117 females crania. The variance analysis of Tukey's revealed, that
crania traits established on the basis of statistical parameters of breadth
length index, and visceral cranium height-breadth index, are significant. In
order to establish statistical characteristics of examined traits, including into
research sexual dimorphism and bilateral differences is also very important.
PMID- 9635355
TI - Microvasculature of the human fetal laryngeal anterior commissure.
AB - The vascular pattern of the injected with Mercox human fetal larynges, especially
of the anterior commissure and surrounding it area, was analysed within the
horizontal and frontal sections under a light microscope. The main result of our
study was confirmation of existence of the avascular "plane zero" situated above
the anterior commissure, which separates that structure from the supraglottic
tier. That finding i.e. avascular separation between teh middle and upper
laryngeal compartments, already present in the fetal period, has clinical
implications as far as the spread of neoplastic process within the larynx is
cancerued.
PMID- 9635356
TI - Selected cases of atypical course of renal and gonadal arteries and veins.
AB - In studies conducted on material comprising 209 individuals of both sexes at the
age of 20 weeks to 90 years, five cases were found with atypical course of renal
and gonadal vessels along with developmental anomalies of the kidneys and
ureters. In three individuals with these anomalies of vessels and ureters some
accompanying complicated organic heart diseases were also detected.
PMID- 9635357
TI - Morphology of the abdominal hemolymph nodes in the Wistar rats.
AB - In 26 Wistar rats the morphology of 30 renal and 20 splenic lymph nodes were
investigated. The left renal nodes are usually singular as compared to multiple
right renal nodes. Microscopically they present segmental structure with
erythroidal elements located mainly in the medullary cords. The splenic nodes, 1
to 5 in number do not show segmental structure but have uniformly dispersed
erythroidal elements.
PMID- 9635358
TI - Variation of the structure and course of the interlobular arteries in human
kidney.
AB - In microangiograms and clearing preparations obtained from 25 adult human
kidneys, the variations of number, origin, length and ramification pattern of the
interlobular arteries were investigated. In the examined material, the
interlobular arteries arose from the arcuate arteries at various angles, most
frequently as a common trunk dividing in its course into 2 to 5 proper
interlobular arteries. Their length was varied in the particular portions of the
renal cortex and correlated with its thickness.
PMID- 9635359
TI - Development of ascending colon in human fetal period.
AB - On the material of 178 fetuses of both sexes, ascending colon development in
fetal period was studied. Variability of its measurements, shapes as well as of
peritoneal and topographic proportions were traced.
PMID- 9635360
TI - Changeability of internal sexual organs of human fetuses basing on their image
computer analysis.
AB - The aim of the paper is computer transformation of the transversal research
results of male (214) and female (178) genital internal organs (examined in 4
months's intervals) in a way enabling longitudinal evaluation.
PMID- 9635361
TI - Morphometric study of the lens in staged human embryos.
AB - In 32 embryos of developmental stages 13 to 23 the measurements of the eye and
lens were made. It was shown that the speed of growth of the eye and lens is at a
maximum between 19 and 23 stages. Beginning from stage 19 the lens acquires
ellipsoidal shape.
PMID- 9635362
TI - The caroticobasilar artery in species of order Perissodactyla.
AB - The caroticobasilar artery was investigated in animals of order Perissodactyla,
in species of Equidae family, and in lowland tapir of Tapridae family. It was
found that the caroticobasilar artery forms homolateral or bilateral anastomosis
between the basilar and internal carotid arteries or in horse and other species
of Equidae family between basilar and caudal intercarotid arteries. The
caroticobasilar artery was found in all species of Equidae family, in all zebras
and in one tapir.
PMID- 9635363
TI - Variations in testicular arteries in fetuses and adults.
AB - An investigation was carried out of 100 human male individuals at the age of 20
hbd to 28 hbd and of 18 to 90 years. Attention was paid to the fact whether these
blood vessels commenced in the aorta or renal artery, to the relation of
testicular arteries to the trunk of vena cava inverior, and to their course vis a
vis that of the renal veins. Four most common variations in the course of these
vessels were identified, and variations in their basic types seen in our material
were described.
PMID- 9635364
TI - Anomaly of the human left renal vein.
AB - A case of the anomalous course of the renal vein is described. The vein trunk is
divided into two crura: a thinner, anterior which passes in front of the
abdominal aorta, and a thicker, posterior which lies behind the aorta. Both crura
terminate in the inferior vena cava.
PMID- 9635365
TI - Metric features of the iliopsoas muscle in late fetuses and adults.
AB - Differences in structure of iliopsoas muscle were documented in studies performed
on 12 human fetuses, aging 37 to 40 weeks of gestational life and on 20 adult
individuals. Results of measurements performed on the muscle were compared
between fetuses of the perinatal age and adult individuals. Indirectly, the
comparison allowed to draw conclusions as to changes in the muscle structure
which take place in between the two developmental stages. The process was
monitoring applying the metric techniques of studies and statistical
interpretation of the results.
PMID- 9635366
TI - Minors: a medical care dilemma.
PMID- 9635367
TI - Medical musical chairs.
PMID- 9635368
TI - The JIM interview John G. Clarkson, MD.
AB - Located in one of the fastest growing areas in the United States, the University
of Miami School of Medicine sits poised to capitalize on an expanding hemispheric
economy. At the same time, the school must also accommodate a burgeoning
competition for Medicare patients with for-profit hospitals. At the helm of the
University of Miami School of Medicine is John G. Clarkson. Clarkson had served
as chairman of the Department of Ophthalmology, Bascom Palmer Eye Institute and
medical director of the Anne Bates Leach Eye Hospital from 1991 to 1995, when he
became dean. He replaced Dean Bernard Fogel who held the position for 14 years.
Interviewed in his office in sunny Miami, Clarkson discussed Miami's approach to
expanding the school's foreign and domestic patient base, developing alliances,
and trying to increase the medical center's profile amongst an increasingly
diverse population.
PMID- 9635369
TI - CXC chemokine modulation of angiogenesis: the importance of balance between
angiogenic and angiostatic members of the family.
PMID- 9635370
TI - The effects of stem cell factor and granulocyte colony stimulating factor therapy
on the activity of the neutrophil NADPH oxidase enzyme system.
AB - BACKGROUND: To explore the effect of cytokine therapy on the NADPH oxidase in
mature myeloid cells, we isolated neutrophils from patients receiving recombinant
human granulocyte colony stimulating factor (G-CSF) and recombinant human stem
cell factor (SCF) and evaluated oxidase activity. All patients had relapsed
neoplastic disease and were at least 3 three weeks since the last course of
chemotherapy or cytokine therapy. METHODS: Stimulus induced superoxide anion (O2
) production in response to PMA (200 ng/mL), fMLP (1 mumol/L), platelet
activating factor (PAF, 2 mumol/L) priming of the fMLP induced response, and
opsonized zymosan OZ (1 mg/mL) was measured. Polymorphonuclear leukocyte (PMN)
subcellular components were prepared, after nitrogen cavitation, by separation on
discontinuous sucrose gradients and NADPH oxidase activity was assessed in a SDS
cell-free system. RESULTS: SCF had no effect on the activity of the neutrophil
oxidase. Neutrophils isolated from patients treated with G-CSF and stimulated
with PMA produced less (superoxide anion) O2- after therapy. PAF priming of the
fMLP induced respiratory burst was also reduced after therapy with G-CSF.
Subcellular NADPH oxidase activity was reduced before cytokine therapy commenced.
This activity did not improve with cytokine treatment. CONCLUSIONS: It appears
likely from this study that G-CSF therapy, with or without SCF, does not cause
significant enhancement of neutrophil NADPH oxidase activity.
PMID- 9635371
TI - Keratinocyte-specific expression of human thrombomodulin in transgenic mice:
effects on epidermal differentiation and cutaneous wound healing.
AB - BACKGROUND: Thrombomodulin is a cell-surface glycoprotein that regulates
coagulation and fibrinolysis. Expression of thrombomodulin by epidermal
keratinocytes is tightly regulated during squamous differentiation and cutaneous
wound healing. METHODS: To determine the consequences of overexpression of
thrombomodulin on squamous differentiation and wound healing in vivo, we
expressed full-length human thrombomodulin in transgenic mice using the human
keratin 14 promoter. Human thrombomodulin was detected in keratinocytes of
transgenic mice by immunohistochemistry and protein C activation assays. Full
thickness cutaneous wounds were created on the dorsum of transgenic mice and
nontransgenic littermates, and allowed to heal for up to 35 days. RESULTS:
Transgenic mice had normal viability and appeared healthy up to one year of age.
In the skin, human thrombomodulin was expressed in basal and suprabasal
keratinocytes, with variable expression in the outer root sheath of hair
follicles. Thrombomodulin activity in neonatal epidermis was 2.5- to 3-fold
higher in transgenic mice than in nontransgenic littermates (p < 0.01). In
cutaneous wounds, human thrombomodulin was expressed in migrating neoepidermal
keratinocytes. No differences in keratinocyte migration or re-epithelialization
were observed between transgenic and nontransgenic mice, but transgenic mice
exhibited delayed collagen bundle deposition within the wound matrix.
CONCLUSIONS: These findings demonstrate that keratinocyte thrombomodulin supports
activation of protein C, and that thrombomodulin activity in epidermis can be
increased by keratinocyte-specific expression of human thrombomodulin in
transgenic mice. Expression of human thrombomodulin in keratinocytes does not
impair normal squamous differentiation or re-epithelialization of cutaneous
wounds, but may modulate collagen reconstitution of the wound matrix.
PMID- 9635372
TI - Fibroblasts from mice with progessive ankylosis proliferate excessively in
response to transforming growth factor-beta 1.
AB - BACKGROUND: Murine progressive ankylosis (MPA) is a spontaneous arthropathy that
produces ankylosis of peripheral and spinal joints in mice homozygous for the
gene ank. This animal model bears a striking resemblance clinically,
radiographically, and histologically to ankylosing spondylitis. Phosphocitrate
(PC) is the only treatment known to significantly delay disease progression in
MPA. Transforming growth factor-beta (TGF-beta) is important for both
developmental bone formation and fracture healing, and has been detected in
biopsy specimens from sacroiliac joints of patient with ankylosing spondylitis.
We hypothesized that TGF-beta might be involved in the pathogenesis of MPA.
METHODS: We compared the proliferative response of resting fibroblasts from
normal and MPA mice to TGF-beta 1 as measured by 3H-thymidine incorporation and
the effect of PC on that response. Cells were cultured with 10% serum as a
positive control. The mouse fibroblast cell line, BALB/3T3, controlled for
culture conditions. RESULTS: MPA and normal fibroblasts responded similarly to
serum. MPA fibroblasts proliferated significantly better in TGF-beta 1 than the
poorly responsive normal mouse fibroblasts. PC, at 10(-3) mol/L, inhibited the
TGF-beta 1-induced proliferation of MPA and 3T3 cells, but had no effect on
normal fibroblasts. CONCLUSIONS: MPA fibroblasts proliferate excessively to TGF
beta 1 in vitro. This effect could be caused by altered TGF receptors, changes in
signal transduction, or impaired inhibition of the TGF-beta signal. This
excessive response is blocked by PC. These results give further clues as to how
PC inhibits the progression of ankylosis in MPA.
PMID- 9635373
TI - Serum levels of a prostaglandin and a leukotriene after thermal mud pack therapy.
AB - BACKGROUND: Mud pack therapy (MPT) influences the serum levels of several
cytokines involved in chondrocyte metabolism and in the pathogenesis of
osteoarthrosis. In fact, we have observed decreases of IL-1 and TNF-alpha,
involved in cartilage inflammation and destruction, and increases of IGF-1 that
have a protective influence on the cartilage. It is known that in osteoarthrosis
MPT is also able to decrease pain, largely attributable to the inflammatory
response. METHODS: We enrolled 31 subjects undergoing MPT and collected blood
samples before and after the therapy to assay serum levels of prostaglandin
(PGE2) and leukotriene (LTB4) compounds with potent inflammatory and algesic
properties. RESULTS: The study shows a decrease in PGE2 and LTB4 serum levels in
all the samples after MPT with no correlation between the PGE2 and LTB4
decreases. CONCLUSIONS: Mud pack therapy exerts a protective effect on the
cartilage and is able to induce pain relief by reducing the inflammatory
reaction.
PMID- 9635374
TI - Acetaldehyde inhibits chymotrypsin and serum anti-chymotrypsin activity.
AB - BACKGROUND: Chymotrypsin (CT) and CT-like enzymes contribute to the dynamics of
metabolism by their participation in digestion, peptide hormone generation and
catabolism, fertilization of ova and inhibition of thrombin-induced platelet
aggregation, among other processes. The frequency of pancreatitis is observably
higher in alcoholics, and pancreatic enzymes have been associated with localized
vascular damage, thrombosis and pancreatic necrosis. METHODS: Since CT is a major
pancreatic enzyme and may serve as a link between pancreatitis, coagulopathy, and
alcoholism, the affect of acetaldehyde (AcH) the primary metabolite of ethanol,
upon the enzyme and upon the influence of human serum thereon was studied.
RESULTS: It was observed that CT activity upon glutaryl-L-phenylalanine-b
naphthylamide was inhibited to the extent of 23.7%, 52.5%, and 96.7% by 44.7,
89.4, and 447 mmol/L AcH in a fluorometric assay whereby the enzyme was dialyzed
to remove excess AcH prior to assay. The p values were < 0.04. Aliquots of human
serum (10 microL, 20 microL, 30 microL, 40 microL, 50 microL, and 100 microL)
inhibited 40 micrograms of CT by 13%, 37.7%, 65.3%, 89.8%, and 92.8%,
respectively (n = 6; p = < 0.05). The serum did not hydrolyze the fluorogenic
substrate. On the other hand, AcH added to serum at 447, 224, 112, or 56 mmol/L
resulted in 42.6%, 42.6%, 52.9%, and 60.3% inhibition of CT relative to a 69.1%
inhibition of the enzyme by serum alone (n = 6; = p < 0.01). CONCLUSIONS: These
data show that AcH clearly decreases the antichymotryptic activity of serum
(consisting of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and alpha
2-macroglobulin). The incomplete inactivation of chymotrypsin by serum and
partial inactivation of CT inhibitor(s) by AcH suggest the possibility that CT
leaked into the circulation, (in alcoholic pancreatitis) may be available in
blood to lower the clotting potential induced by thrombin-activated platelets,
and that a greater amount of CT might be available in the blood of alcoholics,
thereby contributing, in part, to the prolongation of clotting times.
PMID- 9635375
TI - Diagnostic characteristics of cerebrospinal fluid analysis for secondary
menigitis in HIV-infected adults.
AB - BACKGROUND: When human immunodeficiency virus (HIV)-infected patients present
with neurologic problems, lumbar puncture and cerebrospinal fluid (CSF) analysis
are often performed, usually to rule-out the presence of meningitis. However, the
test characteristics of CSF analyses in this population are unknown. METHODS: To
examine the diagnostic characteristics of CSF analyses for secondary causes of
meningitis in HIV-infected adults, we performed a case-control study of 322 HIV
infected adults who received diagnostic lumbar puncture in an urban academic
hospital from 1989 to 1992. Using multivariable logistic regression analyses, we
determined the independent CSF correlates of cryptococcal and other types of
secondary meningitis. RESULTS: Eighty percent were men who had sex with men, 89%
were white, and 85% had AIDS. Thirty-seven case-subjects had a secondary cause of
meningitis though none had bacterial or tuberculous meningitis. Excluding the
india ink as a candidate variable, logistic regression analysis identified 2
independent CSF correlates of secondary meningitis: the leukocyte count (odds
ratio [OR] per 10 cells, 1.2; 95% confidence interval [CI], 1.1 to 1.3), and the
CSF-to-serum glucose ratio (OR per 0.10 units, 0.61; CI, 0.43 to 0.88). The areas
(+/- SD) under the receiver operating characteristic curves were 0.76 +/- 0.05
and 0.72 +/- 0.05, respectively. CONCLUSIONS: In similar clinical settings, these
findings may help clinicians assess the probability of secondary meningitis in
HIV-infected patients when initial CSF results first become available.
PMID- 9635377
TI - Disputed claims for pertussis vaccine injuries under the National Vaccine Injury
Compensation Program.
AB - BACKGROUND: The National Vaccine Injury Compensation Program (NVICP) provides no
fault compensation to victims of serious untoward vaccine reactions under the
supervision of the Department of Health and Human Services (HHS). Special Masters
of the Court of Federal Claims settle compensation disputes that arise between
applicants and program administrators. The majority of published NVICP claim
decisions concern disputes over the cause of neurologic illness or unexpected
infant death following pertussis vaccination. METHODS: Information was collected
from the published decisions to determine the medical characteristics of cases in
which injuries were legally attributed to pertussis vaccination. Because of
practical and statutory restrictions on the application process and the evolving
nature of HHS claim denials, vaccinees in the disputed cases are not
representative of all vaccine casualties, or of all NVICP applicants. RESULTS:
Injuries were blamed on pertussis vaccine in 542 claims disputed by HHS. Claims
asserted that pertussis vaccine caused seizure disorders (333 claims, 189 were
awarded compensation), anaphylaxis (7 claims, 6 awards), hypotonic/hyporesponsive
episodes or other injuries leading to early death (107 claims, 73 awards), and
long-term neurologic disease (51 claims, 18 awards). CONCLUSIONS: Assertions that
pertussis vaccine caused unexpected infant death (other than anaphylaxis),
seizure disorders, and long-term neurologic damage are inconsistent with
epidemiological research. Findings of legal causation may contribute to popular
perceptions that pertussis vaccine is a dangerous biological product. By
providing compensation for these claimants, however, the NVICP may reduce the
number of successful civil suits and thus protect the nation's vaccine supply.
PMID- 9635376
TI - Long-term cytokine alterations following allogeneic blood transfusion.
AB - BACKGROUND: Allogeneic blood transfusion is associated with an increased risk of
infection and higher cancer recurrence rates. Previous research has shown that
blood transfusion results in multiple immune effects, including cytokine
alterations. The purpose of this study was to measure the long term kinetics of
splenocyte cytokine production in transfused mice. METHODS: Balb/c mice received
either syngeneic transfusion (Syn-BT) or allogeneic transfusion (Allo-BT) from
C3H-HeN mice. Splenocyte production of IL-2, IL-6, IL-10, and IFN-gamma was
quantitated by ELISA on post-transfusion days 5, 10, 21, and 30. RESULTS: Both
Allo-BT and Syn-BT produced significant alterations in cytokine production, but
Allo-BT produced the most dramatic and enduring effects as summarized: IL-2:
Production of IL-2 was suppressed at day 5, (p < 0.0001), but then rose, peaking
at day 21, 30% greater than control values (p < 0.05). IL-6: Allo-BT mice showed
suppression of IL-6 throughout the study period (p < 0.005 vs controls, each time
point). IL-10: A 5-fold increase in IL-10 production was seen at day 5 after Allo
BT (p < 0.0001 vs control). Production of IL-10 was suppressed at days 10 and 21
(p < 0.001), but returned to control levels by day 30, gamma-IFN: At day 5 post
Allo-BT, gamma-IFN was 4 x greater than controls (p < 0.0001). Gamma-IFN
production was suppressed at day 10, but then rose at days 21 and 30 to nearly 3
x control levels (p < 0.0001). CONCLUSION: Allo-BT produced multiple cytokine
alterations that were of prolonged duration. These results provide a theoretic
explanation for the multiple, long-term immunomodulating effects seen in patients
who have received transfusions.
PMID- 9635378
TI - "Anything can happen" day.
PMID- 9635379
TI - A public health perspective on optometry-ophthalmology relations.
PMID- 9635380
TI - Traditional versus computer-assisted refraction: "which is better?".
PMID- 9635381
TI - Multiple sclerosis, the great masquerader: an atypical ocular presentation.
AB - BACKGROUND: Multiple sclerosis (MS) is the most common chronic disease of the
central nervous system and is pleomorphic in it presentations. The optic pathways
are frequently involved, and the classic ocular abnormality is optic neuritis.
METHODS: A case is presented of a 23-year-old woman in whom optic neuropathy
developed and multiple sclerosis was diagnosed by neuroradioimaging, in spite of
her lack of awareness of vision loss. RESULTS: The demyelinating lesions in MS
may develop anywhere in the visual system and produce a variety of visual
defects. Magnetic resonance imaging (MRI) is the most sensitive method for
demonstrating these lesions. CONCLUSION: The cause of MS is unknown, but current
opinion holds that autoimmunity--perhaps induced by viral infection--is likely to
be implicated in its etiopathogenesis. Currently, no method for prevention of MS
is known.
PMID- 9635382
TI - Comparison of diagnostic performance and fixation control of two automated
perimeters.
AB - BACKGROUND: The Humphrey perimeter and its Statpac (analysis programs have been
widely used and studied. Another statistical analysis program, FieldView, is used
with the Dicon perimeter. The purpose of this study was to compare the diagnostic
performance of the two perimeters and their statistical analysis packages.
METHODS: Twenty-three normal subjects (age range, 27 to 83 years) and 31 patients
with glaucoma or cerebrovascular disease (age range, 28 to 87 years) experienced
in automated perimetry were examined using the Dicon and the Humphrey perimeters.
RESULTS: The total number of significant points identified on the Humphrey total
deviation probability maps was in close agreement with statistical expectations,
while the Dicon total deviation probability maps yielded significantly more false
positive defects than expected for normals. Fixation loss ratios were almost
twice as high with the Dicon perimeter (mean, 16%) as compared with the Humphrey
perimeter (mean, 9%). The Humphrey perimeter was more reliable than the Dicon in
measuring the defect depth of the physiological blind spot. CONCLUSION: The Dicon
perimeter appears to yield excessive false-positive findings in normal subjects,
resulting in poor sensitivity/specificity combinations, while at the same time
failing to properly measure defect depth in scotomas.
PMID- 9635383
TI - Multiple evanescent white dot syndrome.
AB - BACKGROUND: Multiple evanescent white dot syndrome is a benign, rare, acute,
usually unilateral disease that primarily affects young women. Retinal findings
can include white dots at the level of the retinal pigment epithelium, optic
nerve head swelling, an enlarged blind spot, and paracentral and central
scotomas. Visual loss can be significant early on, but almost always returns to
normal. The cause is unknown. CASE REPORT: A case of a 32-year-old woman with
multiple evanescent white dot syndrome is presented and reviewed. The
progression, symptoms, and differential diagnosis of multiple evanescent white
dot syndrome are reviewed. CONCLUSION: The diagnosis of multiple evanescent white
dot syndrome should be considered in young patients who manifest acute unilateral
vision loss or photopsia. This is particularly important if there is unilateral
disk swelling and blind-spot enlargement.
PMID- 9635384
TI - Orbital pseudotumor: case report and overview.
AB - BACKGROUND: The most common cause of a sudden onset of painful proptosis with
diplopia in an otherwise healthy adult is orbital pseudotumor. However, there are
other conditions that mimic this presentation and must be ruled out with
laboratory testing and imaging studies. CASE REPORT: A 41-year-old Hawaiian man
sought treatment for an acute, progressive, painful, left ophthalmoplegia without
exophthalmos. During the next week, a loss of accommodation and associated
pupillary reaction, decreased visual acuity, color vision deficits, and a
paracentral scotoma developed. CT and MRI revealed a mass in the orbital apex.
All systemic findings were negative, and high-dose systemic steroid therapy was
initiated. Symptoms resolved within hours of the first dose, and signs were
completely absent 1 month later. Follow-up MRI revealed complete absence of the
previously noted mass. CONCLUSION: This is an atypical case of orbital
pseudotumor, since there was no exophthalmos. It was diagnosed by clinical
presentation, laboratory and imaging studies, and response to therapy.
PMID- 9635385
TI - Nodular scleritis: case report involving immunosuppressive therapy.
AB - BACKGROUND: Scleritis is a chronic inflammation of the scleral coat of the eye.
Although the clinical manifestations of scleritis can follow a benign clinical
course, the more serious forms may lead to vision loss and even enucleation of
the eye. METHODS: A case is presented of a 57-year-old woman with a diagnosis of
nodular scleritis and attendant ocular manifestations. RESULTS: Scleritis affects
females slightly more frequently than males, and is most commonly found in
patients who are 40 to 60 years of age. Patients who are symptomatic in only one
eye typically have bilateral involvement within 5 years. More importantly, 50% of
patients with scleritis have an underlying systemic disorder, which makes a
detailed medical history and complete physical examination a crucial part of the
treatment regimen. CONCLUSION: Recognizing the disease and determining the
possible underlying systemic etiologies as early as possible will elucidate the
appropriate treatment options and help suppress the potentially devastating
effects of scleritis.
PMID- 9635387
TI - Pitfalls in industrial drug screening.
AB - Physicians need to establish a protocol for drug testing. Drug testing is, by its
nature, often adversarial. Despite the confusing lack of standardized methods for
handling positive and negative industrial drug tests, both pre-employment and
random, physicians must be methodical in adhering to basic principles of privacy
and careful in the interpretation of positive results. Errors in handling drug
testing have and will continue to lead to avoidable lawsuits.
PMID- 9635386
TI - Comparison of insulin regimens and administration modalities in pregnancy
complicated by diabetes.
AB - PURPOSE: To compare insulin administration using premixed insulin (70% NPH/30%
Regular) by an injectable pen with traditional self-mixed insulin administered by
syringe. METHODS: In this study, 93 women were enrolled into four groups: 1) self
mixed/syringe, 2) premixed/syringe, 3) self-mixed/pen, and 4) premixed/pen.
RESULTS: Women in the premixed pen group had significantly less cesarean
deliveries for failure to progress in labor and a decrease (not significant) in
postpartum infection and infant macrosomia. Patients felt premixed insulin
administered by the pen was easier to use. No significant differences were noted
in glucose control, compliance among the four groups, or cost. CONCLUSION:
Premixed insulin administration via the pen is safe, effective and no more costly
than traditional treatment for pregnant diabetic women.
PMID- 9635388
TI - [Transcription factors and cell differentiation: roles of STAT proteins in
Dictyostelium].
PMID- 9635389
TI - [Pulmonary surfactant proteins: structure, function, pathophysiology].
PMID- 9635390
TI - [Herpes simplex virus type 1-gene: functions and gene therapy].
PMID- 9635391
TI - [Recent development of C-terminal sequence analysis of proteins].
PMID- 9635392
TI - [Microbial endoglycosidases and their application: application of
endoglycosidases which can liberate and transfer sugar].
PMID- 9635393
TI - [Pathological changes of structure in the brain of Alzheimer's disease].
PMID- 9635394
TI - [Preservation of mice strains and databases].
PMID- 9635395
TI - [Live stock database].
PMID- 9635396
TI - [A report from the Protein Data Bank].
PMID- 9635397
TI - [Review of pH measurement (5): pH measurement a la carte].
PMID- 9635399
TI - Evolution and homology of the nervous system: cross-phylum rescues of otd/Otx
genes.
PMID- 9635400
TI - Update CBP/p300 transgenic mice.
PMID- 9635401
TI - Wasted by an elongation factor.
PMID- 9635402
TI - Studies of populations and genetic diseases: mixing it up. Inherited disorders
and their genes in different European populations, Acquafredda di Maratea, Italy,
6-11 February 1998.
PMID- 9635403
TI - Variations on the theme of genomics. Functional genomics: from identifying
proteins to faster drug discovery, Westin City Center Hotel, Washington, DC, USA,
10-11 March 1998.
PMID- 9635404
TI - LCMV cDNA formation: which reverse transcriptase is responsible?
PMID- 9635405
TI - The retinoblastoma gene family: cousins with overlapping interests.
AB - The retinoblastoma tumor suppressor gene (RB1) and its relatives, p107 and p130,
encode a family of proteins that share several properties, including the capacity
to regulate E2F-dependent transcription and inhibit cell-cycle progression.
Although RB1 inactivation is widely implicated in human cancer, the growth
regulatory functions of p107 and p130, and the functional relationships within
the gene family, are emerging only recently. Here we review studies of RB1 gene
family function, with emphasis on in vivo experiments that explore shared and
distinct functions within this family.
PMID- 9635406
TI - Limbs are moving: where are they going?
AB - The past decade has witnessed many changes in the way in which biologists study
vertebrate development. Like curious children, we have progressed from merely
watching and playing with our toys to the more exciting activity of taking them
apart. This progression is mainly due to the application of a number of new
techniques that allow us not only to ablate gene function, but also to induce
gene activity inappropriately in time and space. Through the use of these
techniques we can now disassemble our 'toys' and begin to understand how the
pieces fit together and, thus, we are beginning to understand how the vertebrate
embryo develops. Additionally, the analysis and comparison of limb development in
diverse species has provided much insight into the evolutionary mechanisms
through which changes in developmental pathways have led to the extraordinary
diversity of limbs.
PMID- 9635407
TI - Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box
hypothesis.
AB - The ubiquitin-dependent proteolytic pathway targets many key regulatory proteins
for rapid intracellular degradation. Specificity in protein ubiquitination
derives from E3 ubiquitin protein ligases, which recognize substrate proteins.
Recently, analysis of the E3s that regulate cell division has revealed common
themes in structure and function. One particularly versatile class of E3s,
referred to as Skp1p-Cdc53p-F-box protein (SCF) complexes, utilizes substrate
specific adaptor subunits called F-box proteins to recruit various substrates to
a core ubiquitination complex. A vast array of F-box proteins have been revealed
by genome sequencing projects, and the early returns from genetic analysis in
several organisms promise that F-box proteins will participate in the regulation
of many processes, including cell division, transcription, signal transduction
and development.
PMID- 9635408
TI - A simple mechanism for the avoidance of entanglement during chromosome
replication.
AB - The interphase nucleus of the human eukaryotic cell, before DNA replication,
contains 46 linear DNA molecules, each of the order of centimeters in length, in
a spherical nucleus with a diameter of 3-10 microns. How does the cell avoid
topological entanglements between the 92 linear DNA molecules following
replication? A model of chromosome replication is introduced, based on the
assumption of the existence of a physical linkage between diverging growing forks
during eukaryotic chromosome replication. This basic model is shown to be
sufficient for the avoidance of DNA duplex entanglements during DNA replication.
The model also suggests structural characteristics of chromosomes at various
points in the cell cycle and provides a possible partial mechanism for chromosome
condensation at the end of replication.
PMID- 9635409
TI - Protein annotation: detective work for function prediction.
PMID- 9635410
TI - Protection against carbon tetrachloride hepatotoxicity by oleanolic acid is not
mediated through metallothionein.
AB - Oleanolic acid is a triterpenoid compound that has been shown to protect against
liver injury produced by some hepatotoxicants. This study was designed to
characterize the protective effects of oleanolic acid on carbon tetrachloride
induced hepatotoxicity, and the role of metallothionein in the protection.
Oleanolic acid pretreatment (100-400 micromol/kg, s.c.) protected Sprague-Dawley
rats and mice from carbon tetrachloride-induced liver injury in a dose- and time
dependent manner, as evidenced by serum alanine aminotransferase and sorbitol
dehydrogenase activities, as well as by histopathology. The protection against
carbon tetrachloride hepatotoxicity was not evident until animals were pretreated
with oleanolic acid 12 h, and lasted for 72 h after a single injection. This
suggests that the protection might be due to induction of some adaptive
mechanisms. Metallothionein (MT), an acute-phase protein proposed to decrease
carbon tetrachloride-induced liver injury, was dramatically induced following
oleanolic acid treatment. To examine whether oleanolic acid protection is
mediated through MT, MT-I and II knock-out (MT-null) mice were utilized.
Oleanolic acid pretreatment increased MT levels in control mice (20-fold), but
not in MT-null mice, however, it protected equally against carbon tetrachloride
induced hepatotoxicity in both control and MT-null mice. These data indicate that
oleanolic acid is effective in protecting rats and mice from the hepatotoxicity
produced by carbon tetrachloride, and the protection is not mediated through
induction of MT.
PMID- 9635411
TI - Alteration of acetohexamide reductase activities in kidney microsomes and cytosol
of cadmium-treated rats.
AB - We examined the alteration of acetohexamide reductase activities in kidney
microsomes and cytosol of cadmium (Cd)-treated rats. Acetohexamide reductase
activity in kidney microsomes of male rats was markedly decreased by treatment
with Cd at a dose of 1.23 mg/kg body weight. However, the decreased enzyme
activity was completely restored by repeated treatment with testosterone
propionate. Therefore, it is reasonable to assume that the treatment with Cd
indirectly affect the androgen-dependent acetohexamide reductase activity in
kidney microsomes of male rats, possibly by depressing androgen production. In
the case of female rats, unlike male rats, the microsomal enzyme activity was
little detectable, and was unaffected by the treatment with Cd. Furthermore, Cd
treatment had no significant effect on acetohexamide reductase activity in kidney
cytosol of male or female rats.
PMID- 9635412
TI - Modification of the rate of aging of diisopropylfluorophosphate-inhibited
neuropathy target esterase of hen brain.
AB - This study was aimed to investigate the possibility of modifying the rate of
aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of
hen brain. This reaction on NTE occurs with a half-time of 7.4 min. Atropine was
effective in decreasing the rate of aging on DFP-inhibited NTE and this effect
was time- and concentration-dependent. Atropine was also a weak but progressive
inhibitor of NTE activity (I50 = 80 mM) and this reaction appears to be
reversible at lower atropine concentrations. Among compounds containing oxime
functional groups only OPAB, having longer methylene chain and being more
lipophylic than other oximes usually used in acetylcholinesterase (AChE)
reactivation studies, was effective in decreasing the rate of aging on DFP
inhibited NTE. However, when atropine and oximes were used together we have
obtained a potentiating and/or synergistic effect which was most significant with
combination of atropine and TMB-4 giving up to a 15-fold decrease in the rate of
aging reaction. The efficacy of this particular combination was concentration
dependent. We have also discussed similarities and differences in aging reaction
occurring on NTE and AChE.
PMID- 9635413
TI - Melatonin reduces paraquat-induced genotoxicity in mice.
AB - The protection afforded by melatonin against paraquat-induced genotoxicity in
both bone marrow and peripheral blood cells of mice was tested using micronuclei
as an index of induced chromosomal damage. Melatonin (2 mg/kg) or an equal volume
of saline was injected i.p. into mice 30 min prior to the i.p. administration of
paraquat (two injections of 15 mg/kg; the paraquat injections were given with a
24 h interval) and thereafter at 6 h intervals to the conclusion of the study (72
h). Using fluorescence microscopy, the number of micronuclei in polychromatic
erythrocytes (MN-PCE) per 2000 PCE (1000 PCE/slide) per mouse was counted both in
blood and bone marrow, and the ratio of PCE to normochromatic erythrocytes (NCE)
(PCE/NCE) was calculated. Paraquat treatment increased the number of MN-PCE at
24, 48, and 72 h, both in peripheral blood and bone marrow cells, while no
differences were observed in the PCE/NCE ratio. Melatonin inhibited the paraquat
induced increase in MN-PCE by more than 50% at 48 and 72h. Paraquat toxicity is
believed to be due to free radical generation. Since melatonin is known to be an
efficient free radical scavenger, it is concluded that melatonin's protection
against paraquat-induced genotoxicity is mediated, at least in part, by its free
radical scavenging activity.
PMID- 9635414
TI - Simple spectrophotometric analysis of passive and active ear cutaneous
anaphylaxis in the mouse.
AB - Homologous passive cutaneous anaphylaxis (PCA) and active cutaneous anaphylaxis
(ACA) to ovalbumin and DNP-hapten were studied in the ears of female BALB/c mice
by means of assessing Evans blue dye leakage. For the quantitative evaluation of
PCA and ACA, a hand-held spectrophotometer and the conventional colorimetric
method were used to detect the amount of extravasated dye. The value of deltaE*ab
(a numerical expression of color) obtained with the hand-held spectrophotometer
and the amount of extravasated dye showed a good correlation. In the mouse ear,
the sensitivity of PCA reaction was comparable to that of PCA in the rat, and
deltaE*ab in the PCA and ACA reactions correlated well with the dilutions of sera
and of the antigen, respectively. Thus, using a hand-held spectrophotometer is a
simple, quantitative and sensitive method for ascertaining the extent of
immediate-type hypersensitivity in the mouse.
PMID- 9635415
TI - Lack of histological cerebellar changes in Wistar rats given pulegone for 28
days. Comparison of immersion and perfusion tissue fixation.
AB - Pulegone was given orally by gavage to groups of 28 SPF Wistar rats at dosage
levels of 0 or 160 mg/kg body weight per day for 28 days. Clinically treated
animals showed slackness, depression, decreased food consumption, and body
weight. The loss of body weight was accompanied by a marked decrease in plasma
creatinine. In contrast to earlier results, this study did not reveal occurrence
of cyst-like spaces in the white matter of cerebellum using either perfusion or
immersion tissue fixation techniques. Pulegone increased plasma alkaline
phosphatase and relative liver weight indicating an adverse effect on the liver.
PMID- 9635416
TI - Oxidation of 1,3-butadiene to (R)- and (S)-butadiene monoxide by purified
recombinant cytochrome P450 2E1 from rabbit, rat and human.
AB - 1,3-Butadiene (BD) is a gas used widely in the rubber and plastics industry as an
intermediate in production processes and has been detected in automobile exhaust
and cigarette smoke. BD requires metabolic activation to exert toxicity and has
been shown to be carcinogenic in rodents. IARC has classified BD as a group 2A
(probably carcinogenic to humans) carcinogen. The initial oxidation of BD to
butadiene monoxide (BMO) occurs primarily via cytochrome P450 2E1 and two
stereoisomers of BMO (R and S) can be formed. (R) and (S)-BMO are metabolized
differently and demonstrate markedly different toxicities in isolated rat
hepatocytes. This work examined the generation of (R) and (S)-BMO from BD by
cytochrome P450 2E1 from rabbit, rat and human. BMO level was measured by GC-MS
analysis and enantiomeric composition was determined by GC-FID. The greatest rate
of formation of BMO from BD was obtained with rabbit cytochrome P4502E1 followed
by human and then by rat. Enantiomeric distribution of R and S-BMO produced by
the three species demonstrated no significant differences.
PMID- 9635418
TI - Preventive effect of gamma-glutamylcysteinylethyl ester on carbon tetrachloride
induced hepatic triglyceride accumulation in mice.
AB - The effect of gamma-glutamylcysteinylethyl ester (gamma-GCE), which is a
precursor of reduced glutathione (GSH), on carbon tetrachloride (CCl4)-induced
hepatic triglyceride (TG) accumulation in mice was investigated in comparison
with that of GSH. Administration of gamma-GCE (160 micromol/kg), but not GSH (160
micromol/kg), to mice at 3 h after CCl4 injection (1 ml/kg, i.p.) significantly
attenuated an increase in hepatic TG concentration at 6, 12, and 24 h after the
CCl4 injection. A decrease in hepatic GSH concentration after the CCl4 injection
was significantly diminished by the gamma-GCE administration, but not by the GSH
administration. The correlation coefficient between hepatic TG concentration and
hepatic GSH concentration was -0.627 (P < 0.001) when the results of all mice
were grouped together. These results indicate that gamma-GCE can attenuate CCl4
induced hepatic TG accumulation in mice through the maintenance of hepatic GSH
level.
PMID- 9635417
TI - Histopathological study in B6C3F1 mice chronically exposed by inhalation to
glutaraldehyde.
AB - Glutaraldehyde vapors are irritating for the skin, eyes, nose and lungs;
respiratory symptoms and headaches have been described among workers exposed to
low concentrations of glutaraldehyde far below to 190 ppb. This study was
initiated to determine the chronic effects in mice of inhaled glutaraldehyde
vapors. B6C3F1 mice were exposed using whole-body inhalation chambers, 6 h/day, 5
days/week, for 52 and 78 weeks to 100 ppb, or to filtered air (controls). In
nasal passages at the level of the vestibule, hyperplasia of the squamous
epithelium lining of the dorsal wall and lateral aspect of the atrioturbinate was
observed in a greater number of exposed females than in controls. Epidermal
erosion and ulceration as well as squamous and inflammatory exfoliation were also
seen in the nasal lumens. All these changes were dependent on the length of
glutaraldehyde exposure. The present data suggest that glutaraldehyde long term
exposure only led to changes in nasal passages of female mice but did not induce
mortality and/or tumors in nasal passages, in all mice. These results, along with
the previous subchronic inhalation study of Gross et al., 1994, demonstrates that
in a long term study, chronic glutaraldehyde exposure close to the current
threshold limit values induced lesions at the more anterior part of the nasal
passages in mice and that they likely result from an irritation mechanism (antero
posterior gradient).
PMID- 9635419
TI - The fruit fly: a model organism to study the genetics of alcohol abuse and
addiction?
PMID- 9635420
TI - Drosophila ring canal growth requires Src and Tec kinases.
PMID- 9635421
TI - Why the rat-1 fibroblast should replace the SCN as the in vitro model of choice.
PMID- 9635422
TI - Myogenesis: a view from Drosophila.
PMID- 9635423
TI - A serum shock induces circadian gene expression in mammalian tissue culture
cells.
AB - The treatment of cultured rat-1 fibroblasts or H35 hepatoma cells with high
concentrations of serum induces the circadian expression of various genes whose
transcription also oscillates in living animals. Oscillating genes include rper1
and rper2 (rat homologs of the Drosophila clock gene period), and the genes
encoding the transcription factors Rev-Erb alpha, DBP, and TEF. In rat-1
fibroblasts, up to three consecutive daily oscillations with an average period
length of 22.5 hr could be recorded. The temporal sequence of the various mRNA
accumulation cycles is the same in cultured cells and in vivo. The serum shock of
rat-1 fibroblasts also results in a transient stimulation of c-fos and rper
expression and thus mimics light-induced immediate-early gene expression in the
suprachiasmatic nucleus.
PMID- 9635424
TI - Expanded polyglutamine protein forms nuclear inclusions and causes neural
degeneration in Drosophila.
AB - Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human
neurodegenerative diseases caused by glutamine-repeat expansion. We have
recreated glutamine-repeat disease in Drosophila using a segment of the SCA3/MJD
protein. Targeted expression of the protein with an expanded polyglutamine repeat
led to nuclear inclusion (NI) formation and late-onset cell degeneration.
Differential sensitivity to the mutant transgene was observed among different
cell types, with neurons being particularly susceptible; NI formation alone was
not sufficient for degeneration. The viral antiapoptotic gene P35 mitigated
polyglutamine-induced degeneration in vivo. Our results demonstrate that cellular
mechanisms of human glutamine-repeat disease are conserved in invertebrates. This
fly model will aid in identifying additional factors that modulate
neurodegeneration.
PMID- 9635425
TI - The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC
transporters.
AB - The C. elegans gene ced-7 functions in the engulfment of cell corpses during
programmed cell death. We report that the CED-7 protein has sequence similarity
to ABC transporters, is broadly expressed during embryogenesis, and is localized
to the plasma membrane. Mosaic analysis revealed that ced-7 functions in both
dying cells and engulfing cells during the engulfment process. We propose that
CED-7 functions to translocate molecules that mediate homotypic adhesion between
the cell surfaces of the dying and engulfing cells. Like CED-7, the mammalian ABC
transporter ABC1 has been implicated in the engulfment of cell corpses,
suggesting that CED-7 and ABC1 may be functionally similar and that the molecular
mechanism underlying cell corpse engulfment during programmed cell death may be
conserved from nematodes to mammals.
PMID- 9635426
TI - Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C.
elegans.
AB - The rapid engulfment (phagocytosis) of cells undergoing programmed cell death
(apoptosis) is a fundamental biological process that is not well understood. Here
we report the cloning and functional characterization of ced-6, a gene
specifically required for the engulfment of apoptotic cells in the nematode C.
elegans. The CED-6 protein contains a phosphotyrosine binding domain at its N
terminus and a proline/serine-rich region in its C-terminal half. Genetic mosaic
analysis demonstrates that ced-6 acts within engulfing cells. We also show that
ced-6 can promote the engulfment of cells at both early and late stages of
apoptosis. Our data suggest that CED-6 is an adaptor molecule acting in a signal
transduction pathway that specifically mediates the recognition and engulfment of
apoptotic cells.
PMID- 9635427
TI - Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a
nuclear-encoded mitochondrial metalloprotease.
AB - Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and
spasticity of the lower limbs due to degeneration of corticospinal axons. We
found that patients from a chromosome 16q24.3-linked HSP family are homozygous
for a 9.5 kb deletion involving a gene encoding a novel protein, named
Paraplegin. Two additional Paraplegin mutations, both resulting in a frameshift,
were found in a complicated and in a pure form of HSP. Paraplegin is highly
homologous to the yeast mitochondrial ATPases, AFG3, RCA1, and YME1, which have
both proteolytic and chaperon-like activities at the inner mitochondrial
membrane. Immunofluorescence analysis and import experiments showed that
Paraplegin localizes to mitochondria. Analysis of muscle biopsies from two
patients carrying Paraplegin mutations showed typical signs of mitochondrial
OXPHOS defects, thus suggesting a mechanism for neurodegeneration in HSP-type
disorders.
PMID- 9635428
TI - The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation
congenital hydrocephalus.
AB - Mf1 encodes a forkhead/winged helix transcription factor expressed in many
embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme,
meninges, endothelial cells, and kidney. Homozygous null Mf1lacZ mice die at
birth with hydrocephalus, eye defects, and multiple skeletal abnormalities
identical to those of the classical mutant, congenital hydrocephalus. We show
that congenital hydrocephalus involves a point mutation in Mf1, generating a
truncated protein lacking the DNA-binding domain. Mesenchyme cells from Mf1lacZ
embryos differentiate poorly into cartilage in micromass culture and do not
respond to added BMP2 and TGFbeta1. The differentiation of arachnoid cells in the
mutant meninges is also abnormal. The human Mf1 homolog FREAC3 is a candidate
gene for ocular dysgenesis and glaucoma mapping to chromosome 6p25-pter, and
deletions of this region are associated with multiple developmental disorders,
including hydrocephaly and eye defects.
PMID- 9635429
TI - Ethanol intoxication in Drosophila: Genetic and pharmacological evidence for
regulation by the cAMP signaling pathway.
AB - Upon exposure to ethanol, Drosophila display behaviors that are similar to
ethanol intoxication in rodents and humans. Using an inebriometer to measure
ethanol-induced loss of postural control, we identified cheapdate, a mutant with
enhanced sensitivity to ethanol. Genetic and molecular analyses revealed that
cheapdate is an allele of the memory mutant amnesiac. amnesiac has been
postulated to encode a neuropeptide that activates the cAMP pathway. Consistent
with this, we find that enhanced ethanol sensitivity of cheapdate can be reversed
by treatment with agents that increase cAMP levels or PKA activity. Conversely,
genetic or pharmacological reduction in PKA activity results in increased
sensitivity to ethanol. Taken together, our results provide functional evidence
for the involvement of the cAMP signal transduction pathway in the behavioral
response to intoxicating levels of ethanol.
PMID- 9635430
TI - The preprotein translocation channel of the outer membrane of mitochondria.
AB - The preprotein translocase of the outer membrane of mitochondria (TOM complex)
facilitates the recognition, insertion, and translocation of nuclear-encoded
mitochondrial preproteins. We have purified the TOM complex from Neurospora
crassa and analyzed its composition and functional properties. The TOM complex
contains a cation-selective high-conductance channel. Upon reconstitution into
liposomes, it mediates integration of proteins into and translocation across the
lipid bilayer. TOM complex particles have a diameter of about 138 A, as revealed
by electron microscopy and image analysis; they contain two or three centers of
stain-filled openings, which we interpret as pores with an apparent diameter of
about 20 A. We conclude that the structure reported here represents the protein
conducting channel of the mitochondrial outer membrane.
PMID- 9635431
TI - Dynamin undergoes a GTP-dependent conformational change causing vesiculation.
AB - The dynamin family of GTPases is essential for receptor-mediated endocytosis and
synaptic vesicle recycling, and it has recently been shown to play a role in
vesicle formation from the trans-Golgi network. Dynamin is believed to assemble
around the necks of clathrin-coated pits and assist in pinching vesicles from the
plasma membrane. This role would make dynamin unique among GTPases in its ability
to act as a mechanochemical enzyme. Data presented here demonstrate that purified
recombinant dynamin binds to a lipid bilayer in a regular pattern to form helical
tubes that constrict and vesiculate upon GTP addition. This suggests that dynamin
alone is sufficient for the formation of constricted necks of coated pits and
supports the hypothesis that dynamin is the force-generating molecule responsible
for membrane fission.
PMID- 9635432
TI - GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis.
AB - Dorsal accumulation of beta-catenin in early Xenopus embryos is required for body
axis formation. Recent evidence indicates that beta-catenin is dorsally
stabilized by the localized inhibition of the kinase Xgsk-3, utilizing a novel
Wnt ligand-independent mechanism. Using a two-hybrid screen, we identified GBP, a
maternal Xgsk-3-binding protein that is homologous to a T cell protooncogene in
three well-conserved domains. GBP inhibits in vivo phosphorylation by Xgsk-3, and
ectopic GBP expression induces an axis by stabilizing beta-catenin within Xenopus
embryos. Importantly, antisense oligonucleotide depletion of the maternal GBP
mRNA demonstrates that GBP is required for the establishment of the dorsal
ventral axis in Xenopus embryos. Our results define a family of GSK-3-binding
proteins with roles in development and cell proliferation.
PMID- 9635433
TI - Geminin, an inhibitor of DNA replication, is degraded during mitosis.
AB - We describe a novel 25 kDa protein, geminin, which inhibits DNA replication and
is degraded during the mitotic phase of the cell cycle. Geminin has a destruction
box sequence and is ubiquitinated anaphase-promoting complex (APC) in vitro. In
synchronized HeLa cells, geminin is absent during G1 phase, accumulates during S,
G2, and M phases, and disappears at the time of the metaphase-anaphase
transition. Geminin inhibits DNA replication by preventing the incorporation of
MCM complex into prereplication complex (pre-RC). We propose that geminin
inhibits DNA replication during S, G2, and M phases and that geminin destruction
at the metaphase-anaphase transition permits replication in the succeeding cell
cycle.
PMID- 9635434
TI - Globin gene expression is reprogrammed in chimeras generated by injecting adult
hematopoietic stem cells into mouse blastocysts.
AB - To elucidate whether the differentiation capacity of hematopoietic stem cells
(HSCs) is influenced by specific microenvironments, adult mouse bone marrow
derived HSCs were injected into mouse blastocysts. Embryos developing from
injected blastocysts contained donor-derived cells at various developmental
stages, and progeny of the stem cells were detected in hematopoietic tissues.
Thus, HSCs derived from an adult animal survive after injection into blastocysts
and are able to participate in hematopoietic development. We further find that
the erythroid progeny of transplanted adult HSCs express embryonic/fetal-type
globin genes and, conversely, that embryonic and fetal progenitor cells
transplanted into adult recipients transcribe the adult-type globin gene. Thus,
the developmental potential of adult HSCs is evidently more plastic than
previously thought, and the developmental stage of the hematopoietic
microenvironment controls the developmental fate of transplanted progenitor
cells.
PMID- 9635435
TI - An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase
to anaphase transition in yeast.
AB - Cohesion between sister chromatids during G2 and M phases depends on the
"cohesin" protein Scc1p (Mcd1p). Loss of cohesion at the metaphase to anaphase
transition is accompanied by Scc1p's dissociation from chromatids, which depends
on proteolysis of Pds1p mediated by a ubiquitin protein ligase called the
anaphase promoting complex (APC). We show that destruction of Pds1p is the APC's
sole role in triggering Scc1p's dissociation from chromatids and that Pds1p forms
a stable complex with a 180 kDa protein called Esp1p, which is essential for the
dissociation of Scc1p from sister chromatids and for their separation. We propose
that the APC promotes sister separation not by destroying cohesins but instead by
liberating the "sister-separating" Esp1 protein from its inhibitor Pds1p.
PMID- 9635436
TI - The small GTP-binding protein RhoA regulates a delayed rectifier potassium
channel.
AB - Tyrosine kinases activated by G protein-coupled receptors can phosphorylate and
thereby suppress the activity of the delayed rectifier potassium channel Kv1.2.
Using a yeast two-hybrid screen, we identified the small GTP-binding protein RhoA
as a necessary component in this process. Coimmunoprecipitation experiments
confirmed that RhoA associates with Kv1.2. Electrophysiological analyses revealed
that overexpression of RhoA markedly reduced the basal current generated by Kv1.2
expressed in Xenopus oocytes. Furthermore, in 293 cells expressing Kv1.2 and ml
muscarinic acetylcholine receptors, inactivating RhoA using C3 exoenzyme blocked
the ability of ml receptors to suppress Kv1.2 current. Therefore, these results
demonstrate that RhoA regulates Kv1.2 activity and is a central component in the
mechanism of receptor-mediated tyrosine kinase-dependent suppression of Kv1.2.
PMID- 9635437
TI - Histopathological, lymphoscintigraphical, and immunological changes in the
inguinal lymph nodes of rhesus monkeys during the early course of infection with
Brugia malayi.
AB - The relationship of the early lymphatic pathophysiological alterations with those
of tissue inflammatory and cellular responses in the inguinal lymph nodes of
Brugia malayi-infected rhesus monkeys was examined. Each of five animals was
inoculated subcutaneously in the right calf with 200 third stage larvae (L3) and
5 weeks later, before the onset of patency [10 to 12 weeks postinoculation (PI)],
their right inguinal nodes began to show signs of enlargement, becoming most
prominent between weeks 10 to 16 PI. Histopathologically, the right nodes had
eosinophilic lymphadenitis, lymphoid hyperplasia, and pronounced germinal
centers. Lymphoscintigraphy using 99mTc-antimony trisulfide colloid showed
pathophysiological alterations of the lymph flow rate in the right leg but not in
the left leg at weeks 7 and 15 PI. In vitro blastogenesis to B. malayi antigens
at week 10 PI showed the inguinal lymph node cells proliferated more vigorously
than did peripheral blood cells early in infection. However, at week 24 PI both
lymph node and peripheral blood cells proliferated to antigens. Flow cytometry
showed an upregulation of HLA-DR+ lymphocytes in right lymph node cells from
infected animals when compared to those from control animals. No changes in CD2,
CD4, CD8, CD20, CD29, and CD45R cell numbers in lymph node of infected animals
were seen when compared to control animals. Our results show that lymphatic
pathology occurs early before the onset of patency, correlating with a marked
tissue inflammatory and cellular responses of lymph node cells in B. malayi
infected rhesus monkeys. The rhesus could be an extremely useful model for
understanding the evolution of pathology and pathogenesis of the disease.
PMID- 9635438
TI - Leishmania (Leishmania) amazonensis: purification and enzymatic characterization
of a soluble serine oligopeptidase from promastigotes.
AB - A soluble proteinase was purified 90-fold from extracts of promastigotes of
Leishmania (Leishmania) amazonensis using a combination of ion-exchange
chromatography in Q-Sepharose Fast Flow, gel filtration chromatography in
Sephacryl HR S-200, and chromatofocusing. The enzyme appeared as a single band
with an apparent molecular weight of 101 kDa by silver staining following SDS
PAGE, under both reducing and nonreducing conditions. The proteinase has a pH
optimum between 8.0 and 8.5 and an isoelectric point between 5.12 and 5.23,
belongs to the serine proteinase class, and is inhibited by Mg2+, Ca2+, and K+.
The primary specificity determined using synthetic substrates is for basic amino
acids. The kinetic parameters for the Bz-L-Arg-Nam substrate are Km = 26 microM,
kcat = 32 min(-1), and Ksi = 1270 microM (the proteinase showed inhibition by
excess substrate). The enzyme does not hydrolyze casein, albumin, and gelatin or
large peptides like the oxidized insulin B chain, but hydrolyzes small peptides
like bradykinin and fragment 4-10 of the adrenocorticotropic hormone, at the
carboxyl side of basic residues and aromatic residues preceding basic residues.
The enzyme appears, thus, to be restricted in its action, cleaving only small
peptide substrates, which characterizes the proteinase as an oligopeptidase. This
is the first report of purification of a serine peptidase from Leishmania species
and it increases the short list of known oligopeptidases.
PMID- 9635439
TI - Leishmania: amastigotes synthesize conserved secretory acid phosphatases during
human infection.
AB - Leishmania donovani is the major causative agent of Old World human visceral
leishmaniasis (VL). In vitro, both promastigotes and axenic amastigotes of L.
donovani constitutively secrete soluble acid phosphatases (SAcPs), which contain
conserved antigenic epitopes. These SAcPs are the most abundant and best
characterized secretory proteins of this parasite. The aim of this study was to
determine whether this enzyme was produced by intracellular amastigotes during
the course of human infection. To that end, sera from acutely infected
leishmaniasis patients were tested for anti-SAcP antibodies using L. donovani
promastigote culture supernatants. Our results showed that VL patient sera from
different endemic foci immunoprecipitated parasite SAcP enzyme activity. Further,
these VL patient sera recognized the 110- and 130-kDa SAcPs in both Western blots
and radioimmunoprecipitation assays. Results of tunicamycin experiments
demonstrated that VL patient anti-SAcP antibodies were directed against the
polypeptide backbone of the parasite SAcPs. In addition, both radiolabeled L.
donovani SAcPs and native enzyme activities were immunoprecipitated by sera from
patients with various forms of cutaneous leishmaniasis. Together, these studies
demonstrate that Leishmania amastigotes produce SAcPs during the course of human
infections.
PMID- 9635440
TI - Fasciola hepatica: stage-specific expression of novel gene sequences as
identified by differential display.
AB - Differences in gene expression between adult and immature Fasciola hepatica
(liver fluke) parasites isolated from the mammalian host were investigated using
the technique of differential display. For any given primer combination used to
produce these displays there were, on average, 22% apparently adult-specific and
14% apparently immature-specific cDNA products able to be identified, consistent
with a high degree of differential gene expression between these two parasite
developmental stages. Several cDNA fragments specific to immature parasite RNA
were isolated and cloned. An abundant 400- to 500-bp RNA species was identified
on a Northern blot by hybridization to the cloned DD2 cDNA fragment and was
determined to be expressed at levels at least 10-fold higher in immature
parasites relative to adult parasites. mRNA transcripts corresponding to the
remaining cDNA fragments (DD14, DD16, DISP10, and DISP2) were apparently
expressed at levels below the sensitivity limits of Northern analysis, although
differential expression of these transcripts was confirmed by reverse
transcriptase PCR (RT-PCR). The identities or functional significance of each of
the five differentially expressed cDNAs identified in this study is still unclear
due to the lack of any significant sequence similarity to the entries currently
held within sequence databases.
PMID- 9635441
TI - Biomphalaria spp: identification of the intermediate snail hosts of Schistosoma
mansoni by polymerase chain reaction amplification and restriction enzyme
digestion of the ribosomal RNA gene intergenic spacer.
AB - The intermediate hosts of S. mansoni in South America, B. glabrata, B.
tenagophila, and B. straminea, were identified by restriction fragment length
polymorphism (RFLP) analysis of the internal transcribed spacer region of the
rRNA gene. The restriction patterns obtained with DdeI were the most informative
of the eight enzymes that were tried. The RFLP profiles obtained using this
enzyme are highly distinctive and exhibit low levels of intraspecific
polymorphism even between specimens collected from diverse regions of Brazil,
Argentine, Paraguay, and Uruguay. The method proved useful for the identification
of DNA extracted from eggs, permitting species identification while preserving
the living adult specimens for further studies.
PMID- 9635442
TI - Trypanosoma cruzi 175-kDa protein tyrosine phosphorylation is associated with
host cell invasion.
AB - We examined the requirement of Tropanosoma cruzi protein tyrosine phosphorylation
for parasite entry into mammalian cells and analyzed the profile of
phosphorylated proteins in infective trypomastigotes. Treatment of metacyclic or
tissue culture trypomastigotes with genistein, an inhibitor of protein tyrosine
kinase activity, significantly inhibited invasion of cultured HeLa cells. A
soluble factor, contained in HeLa cell extract and absent in the extract ot T.
cruzi-resistant K562 cells, greatly enhanced phosphorylation levels of a 175-kDa
protein (p175) in trypomastigotes. Genistein inhibited p175 tyrosine
phosphorylation. P175 was undetectable in noninvasive epimastigotes. The
phosphorylation-inducing activity of HeLa cell extract was abrogated by
adsorption with metacyclic trypomastigotes but not with epimastigotes or when it
was mixed with recombinant protein J18, which contains the entire peptide
sequence of gp82, a metacyclic stage-specific surface glycoprotein implicated in
target cell invasion. These data suggest that, in metacyclic trypomastigotes,
gp82 is the signaling receptor that mediates protein tyrosine phosphorylation
necessary for host cell invasion.
PMID- 9635443
TI - Trichomonas vaginalis and Tritrichomonas foetus: expression of chitin at the cell
surface.
AB - The expression of chitin as a structural component of Trichomonas vaginalis and
Tritrichomonas foetus was demonstrated by using enzymatic hydrolysis by
recombinant (rec-) chitinase, chemical analysis, lectin, fluorescent Calcofluor
and antibody binding, glycosidases of known specificity, high-performance liquid
chromatography (HPLC), and flow cytometry. Chitinous structures were
characterized by their insolubility in hot alkali and by releasing glucosamine on
hydrolysis with 6 N HCl. N,N'-Diacetylchitobiose and N,N,'N''
triacetylchitotriose were identified by HPLC as enzymatic hydrolysis products of
the alkali-resistant polysaccharide. The location of chitin on the surface of T.
vaginalis and T. foetus was inferred from the decreased reactivity with whole
parasites of ligands such as Lycopersicon esculentum (TOL) and Solanum tuberosum
lectins, fluorescent Calcofluor, and anti-chitin antibody, after cell treatment
with rec-chitinase. Binding of [125I]TOL showed that, in T. vaginalis and T.
foetus, the numbers of lectin receptors per cell were 4.2 x 10(5) and 3.0 x
10(5), respectively. Binding of the lectin to the trichomonad surface was
markedly decreased by treatment with rec-chitinase. TOL interaction with the
parasites was not affected by N-acetyl-beta-D-glucosaminidase treatment, showing
that the lectin receptors consisted of beta-linked GlcNAc polymers and not of
terminal beta-linked GlcNAc residues.
PMID- 9635444
TI - Efficacy of ivermectin against Strongyloides stercoralis infection in jirds
(Meriones unguiculatus).
AB - The activity and distribution of ivermectin (IVM), a broad spectrum anthelmintic
for various nematodes and arthropods, was tested against Strongyloides
stercoralis infection in the jird (Meriones unguiculatus.) The pattern of IVM
concentration in the serum of jirds after either low- (200 microg/kg) or high
dose (1000 microg/kg) treatment by intraperitoneal injection showed a typical
single-peak profile with the maximum drug levels detected at 1 h followed by a
rapid decline to undetectable values by 48 h posttreatment. With equivalent IVM
doses, the serum levels in male jirds were significantly higher than those
observed in female jirds at 1 and 12 h posttreatment (P < 0.05). Low-dose IVM
treatment of either male or female jirds, in comparison with that of the
respective control groups, produced no observable effect on the adult worm burden
or the parasite fecundity. The curative dose for S. stercoralis in both sexes of
animals was achieved when using the high dose of 1000 microg/kg of IVM. The area
under the curve calculated from the serum-concentration profiles in males was
significantly higher than that for females after the high-dose treatment of IVM
(P < 0.05). By low-dose treatment, a significantly lower adult worm burden was
observed in males compared with that in females (P < 0.05), and this difference
correlated with the higher serum levels of IVM in male animals. The distribution
of IVM in the jird after high-dose treatment was characterized by initial
appearances at 1 h of maximum levels of the drug in the serum and intestinal
content. The maximum level in the feces was reached at 12 h posttreatment and
rapidly declined thereafter. The level in the intestinal tissue was comparatively
much lower than that in the intestinal content and the feces. The half-life of
IVM in the intestinal content (49.5 h) was longer than those in the serum, feces,
and intestinal tissue (6.53-13.07 h). Analyses of the relationship between the
peak serum IVM occurring at 1 h posttreatment and the adult worm recovery
revealed that the minimal serum concentration associated with clearance of the
adult worm from the jird was approximately 0.65 microg/ml. The jird-S.
stercoralis model has not only made studies on various aspects of parasite
biology possible, but also provided an in vivo system to examine the efficacy as
well as the mode of action of IVM against this intestinal nematode.
PMID- 9635445
TI - Ixodes scapularis: salivary kininase activity is a metallo dipeptidyl
carboxypeptidase.
AB - Saliva and salivary gland homogenates of Ixodes scapularis contain a dipeptidyl
carboxypeptidase activity that accounts for the previously described salivary
kininase activity of this tick. Reversed phase HPLC and laser desorption mass
spectrography of the reaction products identified bradykinin fragment 1-7 and 1-5
as being produced subsequent to incubation of purified salivary kininase with
bradykinin. The activity was inhibited by captopril and EDTA and was activated by
cobalt and manganese, a behavior similar to that displayed by angiotensin
converting enzymes of vertebrate and invertebrate origins.
PMID- 9635446
TI - Schistosoma mansoni: the varying occurrence of repetitive elements in different
strains shows sex-specific polymorphisms.
AB - The repetitive elements W1, W2, and D9 were shown before to be female specific in
the Puerto Rican strain of Schistosoma mansoni. In the Liberian strain, however,
W1 was detected in both sexes. Therefore, a strain- and sex-specific analysis of
the presence of all three repetitive elements has been performed in different
schistosome strains. For this analysis, W2 has been isolated and characterized,
whereas W1 and D9 were already available. We demonstrate the presence of the W2
element in both sexes in the Liberian strain, which coincides with W1.
Furthermore, it is shown that elements W1 and W2, but not D9, can be found in
both sexes of the majority of the other strains investigated. We even found an
isolate of the Puerto Rican strain with W1 and W2 elements in females and males.
This finding contradicts results reported in the literature that demonstrated
that W1 and W2 are female specific for the Puerto Rican strain. The data of this
study indicate sex-specific polymorphisms, probably associated with the sex
chromosomes in schistosomes.
PMID- 9635447
TI - Theileria annulata: the expression of two novel macroschizont antigens on the
surface of infected mononuclear cells differs during in vitro attenuation of a
virulent cell line.
AB - The first part of this study of the biological mechanisms underlying attenuation
of virulent Theileria annulata macroschizont-infected cell lines screened four
pairs of T. annulata (Hisar) in vivo- and in vitro-derived macroschizont-infected
cell lines (lines) and identified a single in vivo-derived line, which induced
lethal tropical theileriosis. The other seven lines were relatively avirulent.
Analysis of the clinical, hematological, and parasitological responses of cattle
immunized with different passages of the virulent line after in vitro culture
showed that it was partly attenuated by passage (p) 50 and avirulent by p130.
Clones representing the three glucose phosphate isomerase (GPI) isotypes, which
constituted the newly isolated virulent culture, were obtained from p3 by
limiting dilution; p50 and p130 consisted of one isotype. The second part of the
study raised monoclonal antibodies (MAbs) against macroschizont-infected cells,
as reagents for detecting antigenic differences between virulent and avirulent
parasites, and identified two MAbs that recognized the surface of infected cells
as well as macroschizonts. MAb EU1 recognized an antigen expressed by all the
lines tested, whether in vitro- or in vivo-derived, whether uncloned or cloned,
and irrespective of extent of subpassage in culture. MAb EU106 recognized an
antigen whose expression by the virulent line and its clones disappeared on
passage in culture. This antigen was not expressed at all by the avirulent in
vitro-derived line prepared with cells from the same calf. Both antigens were
expressed by lines infected with other stocks of T. annulata, including two lines
known to induce lethal disease. The different profiles of expression of the two
novel antigens, recognized by MAbs EU1 and EU106, by the line undergoing
attenuation suggest (1) that the two antigens interact differently with the
bovine immune system; and (2) that there are two, very different, potential roles
for these antibodies in the development of vaccines against T. annulata
infections.
PMID- 9635448
TI - Trichomonas vaginalis: in vitro phagocytosis of lactobacilli, vaginal epithelial
cells, leukocytes, and erythrocytes.
AB - This paper explores the interaction of two strains of Trichomonas vaginalis, of
high and low virulence, with the cell types present in the microenvironment of
the parasite during human infections. With the use of transmission and scanning
electron microscopy the sequence of internalization by T. vaginalis of
Doderlein's lactobacilli, and of vaginal epithelial cells, leukocytes, and
erythrocytes was documented. Furthermore, the degradation of ingested material by
colocalization of acid phosphatase activity in phagocytic vacuoles was
demonstrated. Phagocytosis of all cell types analyzed was found in both strains
studied, although the highly virulent strain internalized target cells more
rapidly than the less virulent one. Ultrastructural evidence indicated that
phagocytosis takes place through two distinct mechanisms, only one involving the
formation of a phagocytic stoma, characteristic of professional phagocytes. T.
vaginalis phagocytosis may be both an efficient means of obtaining nutrients for
the parasite and a significant factor in the pathogenesis of trichomonal
infections of the human genitourinary tract.
PMID- 9635449
TI - Trypanosoma cruzi: a novel chemical class (nitrobenzofurans) active against
infections of mice (Mus musculus).
PMID- 9635450
TI - Anisakis simplex: mutational bursts in the reactive site centers of serine
protease inhibitors from an ascarid nematode.
PMID- 9635451
TI - Plasmodium falciparum: parasite typing by using a multicopy microsatellite
marker, PfRRM.
PMID- 9635452
TI - Genus-specific expression from the SL RNA promoter of Leishmania amazonensis.
PMID- 9635453
TI - Incidence of frontal sinusitis following partial middle turbinectomy.
AB - The role of partial middle turbinate resection as an adjunct to endoscopic sinus
surgery is controversial. Recent literature suggests that middle turbinate
resection may have a detrimental effect on the frontal sinus. A retrospective
analysis of 155 consecutive patients undergoing partial middle turbinate
resection utilizing the technique of the senior author (J.A.D.) for either
sinusitis or nasal obstruction was conducted. The data reveal a low rate of
frontal sinusitis following partial middle turbinectomy (10%). None of the
patients undergoing partial middle turbinectomy for nasal obstruction developed
frontal sinusitis postoperatively. No major complications were encountered.
Frontal sinusitis following middle turbinectomy was often associated with
preoperative comorbidity such as asthma, nasal polyps, severe disease score on
computed tomography, or diseased middle turbinates. The authors conclude that
partial middle turbinectomy for treatment of sinusitis and nasal obstruction has
a low incidence of postoperative frontal sinusitis. Development of frontal
sinusitis may be predictable on the basis of several comorbid factors.
PMID- 9635454
TI - Biomechanics of arytenoid adduction surgery in an ex vivo canine model.
AB - The biomechanics of arytenoid adduction surgery are not well understood. An
excised canine larynx model was used to study the effects of variable suture
tension on glottal configuration and on vocal fold tension (at the midfold and
the vocal process). Arytenoid adduction both medializes the vocal fold and closes
a posterior glottal chink. Vocal fold tension at the midfold did not vary
significantly with suture tension. As suture tension increased to approximately
100 g, vocal fold tension at the vocal process also increased. Beyond 100 g of
suture tension, vocal fold tension at the vocal process did not increase. We
conclude that the effects of suture tension on the resistance to lateral movement
are different at the midfold compared to the vocal process. Procedures for
surgical rehabilitation of vocal fold paralysis should address the biomechanical
subunits of the larynx individually in order to achieve optimum results.
PMID- 9635455
TI - Cervicomedullary compression: an unrecognized cause of vocal cord paralysis in
rheumatoid arthritis.
AB - Cervicomedullary compression (CMC) from traumatic, infectious, or congenital
processes of the atlanto-axial joint is a known cause of vocal cord immobility.
Cervicomedullary compression can also occur from destructive arthritic changes
and inflammatory pannus formation at the occipito-atlanto-axial joint in patients
with rheumatoid arthritis (RA). We present findings suggesting that CMC in
patients with RA is an unrecognized cause of vocal cord immobility. Previously,
vocal cord immobility in patients with RA has been assumed to be cricoarytenoid
arthritis with joint fixation. We report 3 patients with RA and radiographically
demonstrated CMC with vocal cord immobility. One patient had bilateral vocal cord
immobility and airway obstruction; 2 patients had unilateral cord paralysis and
contralateral paresis without airway compromise. All patients had myelopathy and
neck pain in addition to brain stem symptoms. All patients underwent transoral
transpharyngeal decompression of the anterior craniocervical junction with
subsequent posterior fusion. These patients demonstrated full return of vocal
cord function within 3 months of decompression. We propose that CMC is a cause of
vocal cord paralysis in patients with RA that may go unrecognized without
appropriate imaging studies of the skull base and physician awareness of symptoms
of occipito-atlanto-axial subluxation and/or basilar invagination with brain stem
compression. Our results demonstrate that CMC in RA is a potentially reversible
cause of vocal cord paralysis.
PMID- 9635456
TI - Microvascular lesions of the true vocal fold.
AB - Microvascular lesions, also called varices or capillary ectasias, in contrast to
vocal fold polyps with telangiectatic vessels, are relatively small lesions
arising from the microcirculation of the vocal fold. Varices are most commonly
seen in female professional vocalists and may be secondary to repetitive trauma,
hormonal variations, or repeated inflammation. Microvascular lesions may either
be asymptomatic or cause frank dysphonia by interrupting the normal vibratory
pattern, mass, or closure of the vocal folds. They may also lead to vocal fold
hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in
determining the functional significance of vocal fold varices. Management of
patients with a varix includes medical therapy, speech therapy, and occasionally
surgical vaporization. Indications for surgery are recurrent hemorrhage,
enlargement of the varix, development of a mass in conjunction with the varix or
hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy
due to a functionally significant varix.
PMID- 9635457
TI - Assessment of vocal function using simultaneous aerodynamic and calibrated
videostroboscopic measures.
AB - Despite many attempts to model how vocal fold movements relate to the aerodynamic
forces acting on them during phonation, there have been few simultaneous
measurements of glottal area and transglottal air pressures and flows. A novel
system is described that combines endoscopic measurement of glottal area with
aerodynamic flow and pressure measures made during phonation. Results from bench
top model tests and from one human subject are presented. For both tests, an
aerodynamic model of airflow through a constriction was used to predict the area
of the constriction (glottis), and these predictions were compared with
endoscopic measurements. The results showed good correlation between predicted
and observed areas; however, for small constrictions (<0.025 cm2), whether
artificial or glottal, the errors in estimating areas with either optical or
aerodynamic methods increase significantly. These results suggest that this
measurement system has the potential to enhance the assessment of vocal function.
PMID- 9635458
TI - Revision surgery for chronic otitis media: a learning experience. Report on 389
cases with a long-term follow-up.
AB - The objective of this study was to evaluate, during a long-term follow-up period,
the results of revision surgery for chronic otitis media with or without
cholesteatoma. Intact canal wall and canal wall down procedures were performed.
The surgical history of every patient was assessed before the operation. A dry,
relatively safe, and disease-free ear was created in 90% of the reoperated ears
(N = 389). The recurrence rate of cholesteatoma was 5% for the total group.
Reperforations of the tympanic membrane occurred in 10%, and persistent or
recurrent otorrhea was present in 10% of cases. The functional hearing results
were quite satisfactory. A residual air-bone gap of < or =30 dB was reached in
70.3% of the cases after revision tympanoplasty only (N = 41). Revision
mastoidectomy with revision tympanoplasty as a one-stage procedure led
subsequently, in 76% of intact canal wall procedures (N = 113) and 55% of canal
wall down procedures (N = 98), to a residual air-bone gap of < or =30 dB.
PMID- 9635459
TI - Cochlear implantation in children with inner ear malformations.
AB - We performed a case study and intervention study, with follow-up of 1 to 5 years,
in 4 children with inner ear malformations who underwent implantation of a
multichannel cochlear implant (Nucleus, Cochlear Corporation) at ages 3 to 12
years. Malformations included a common cavity deformity, 2 incomplete partitions,
and 1 case of isolated bilateral vestibular aqueduct enlargement. One child had a
single-channel implant placed at 3 years of age, and this was exchanged for a 22
channel implant at age 9. One child had her implant placed at age 4.5 years, but
due to complications from a cerebrospinal fluid (CSF) leak had the initial
implant removed and replaced at age 5 years during repair of the CSF leak.
Intraoperative findings included a CSF leak at the time of surgery in 3 patients.
One patient contracted bacterial meningitis 7 months postimplantation that was
thought to be secondary to acute otitis media in the unoperated ear. Bilateral
CSF leaks were noted in the middle ear by a lumbar puncture radionuclide and
fluorescein dye study. Successful repair of the CSF leaks and reimplantation of
the cochlear implant was carried out in this patient. Mapping and programming of
the implant was found to be challenging in each of these patients. All patients
demonstrated improved performance after implantation. Two patients demonstrated
some open-set speech perception. One patient demonstrates improved use of
temporal cues in a structured closed set. One patient has achieved no significant
speech recognition at this time, but does have improved sound detection and
awareness. Cochlear implantation in children with congenital inner ear
abnormalities can be a successful method of rehabilitation. It should be
recognized that the postoperative speech perception results may be highly
variable among patients, and that intraoperative complications may occur.
PMID- 9635460
TI - Upregulation of messenger RNA for inflammatory cytokines in middle ear mucosa in
a rat model of acute otitis media.
AB - A rat model for acute otitis media has been established and was used to delineate
the temporal expression of messenger RNA for key inflammatory cytokines.
Inoculation with live Streptococcus pneumoniae induced a rapid expression of
tumor necrosis factor alpha (within 6 hours) followed by upregulation of message
for interleukin (IL)-6 (peak at 12 to 24 hours, remaining elevated through 120
hours) and IL-10 (peak at 24 hours). Inducible nitric oxide synthase message was
also selectively increased following live bacterial inoculation (peak at 12 to 24
hours). Although there was a detectable inflammatory response to killed bacteria,
it was minimal, was of short duration, and preceded the peak for live bacteria;
only expression of IL-6 was significantly increased in this group (peak at 12
hours, remaining elevated through 72 hours). We interpret this to be due to an
inflammatory response to bacterial products (such as lipopolysaccharide) in the
heat-killed bacterial inoculum. The phosphate-buffered saline (PBS)-inoculated
group exhibited a transient increase of IL-6 message, which indicates that this
cytokine is a sensitive marker of the acute response to trauma. Otherwise, PBS
invoked only a slight reaction in the mucosa with respect to the other
inflammatory mediators being measured.
PMID- 9635461
TI - Comparative evaluation of culture and PCR for the detection and determination of
persistence of bacterial strains and DNAs in the Chinchilla laniger model of
otitis media.
AB - This study was designed to determine the persistence of culturable bacteria
versus DNA in the presence of a middle ear effusion in a chinchilla model of
otitis media. Cohorts of animals were either infected with an ampicillin
resistant Haemophilus influenzae strain or injected with a tripartite inoculum
consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella
catarrhalis; and DNA from H influenzae. The H influenzae-infected animals
displayed culture positivity and polymerase chain reaction positivity through day
35. In the chinchillas infected with the low-copy number inocula of S pneumoniae,
DNA was not detectable after day 1 from the co-inoculated pasteurized M
catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA
from the live low-copy number bacteria persisted through day 21 even though they
were not culture-positive past day 3. These results demonstrate that DNA, and DNA
from intact but nonviable bacteria, does not persist in an amplifiable form for
more than a day in the presence of an effusion; however, live bacteria, while not
culturable, persist in a viable state for weeks.
PMID- 9635462
TI - Sarcoidosis of the external nose mimicking rhinophyma. Case report and review of
the literature.
AB - A 52-year-old man with a large external nasal mass is presented. Initially, the
mass was thought to be rhinophyma, but biopsy of the mass revealed noncaseating
granulomata consistent with sarcoidosis. The mass resolved following several
steroid injections. The case is discussed in detail, along with a review of the
literature pertaining to sarcoidosis of the nose and nasal cavity.
PMID- 9635463
TI - Branchial cleft cyst carcinoma: myth or reality?
AB - Skepticism has surrounded the existence of branchial cleft carcinoma since the
entity was first described in 1882. However, a landmark work of 1950 established
four criteria for the diagnosis of branchial cleft carcinoma, the most important
criterion being histologic proof of carcinoma arising from a normal cyst
epithelium. Of the 43 cases found in an extensive review of the literature, only
7 cases have satisfied all four of the criteria. To this we add 2 patients who
had recurrent infections of a cervical cyst as children and later developed
carcinoma within these structures. Additionally, we propose a minor modification
to the 1950 criteria and a paradigm for diagnosis and management of these
lesions.
PMID- 9635464
TI - Age-related changes in the human laryngeal glands.
AB - The present study was conducted to determine age-related changes in the human
laryngeal glands by means of excised human adult larynges. Scanning and
transmission electron microscopic observations were made. The results obtained
are summarized as follows. 1) Granular endoplasmic reticulum and Golgi apparatus
were sparse in the cytoplasm of serous and mucous cells. 2) Secretory granules in
serous cells had decreased in number. 3) Secretory granules were less electron
dense compared to those in younger adult specimens, but were electron-lucent. 4)
Mucigen droplets in mucous cells were not as numerous as those in younger adults.
5) Discharge of secretory granules and mucigen droplets had decreased. 6) Age
related morphologic changes in the laryngeal glands influenced not only the
amount but also the quality of secretions. 7) The above changes lessened
lubrication of the vocal folds, thus causing aging of the voice to some extent.
8) Local immunity and mucociliary transport were also affected. 9) Age-related
changes in the laryngeal glands partially altered laryngeal function.
PMID- 9635465
TI - Magnetic resonance sialography.
PMID- 9635466
TI - Internal carotid artery aneurysm presenting as an unusual nasopharyngeal mass.
PMID- 9635467
TI - Regional and distant metastases in laryngeal and hypopharyngeal sarcomas.
AB - Cervical node and distant metastases are the most important prognostic factors in
malignant laryngeal neoplasms. Owing to the unusual occurrence of laryngeal
sarcomas, the prevalence of their metastases has never been analyzed in detail.
We reviewed the laryngeal sarcomas reported in the literature and noticed that
both regional and distant metastases are rare events and variable for different
histotypes. These observations have obvious therapeutic and prognostic
implications.
PMID- 9635468
TI - Neurological and neuropsychological bases of empathy.
AB - Impairments of social behavior after cerebral damage are often problematic and
difficult to assess and manage, with few models addressing evaluation, treatment
options and prognosis. Recent studies suggest that a fundamental mechanism of
social behavior disturbed by acquired cerebral damage is empathy. Empathy refers
to the cognitive and emotional processes that bind people together in various
kinds of relationships that permit sharing of experiences as well as
understanding of others. Empathic changes are particularly evident after focal
prefrontal cortex damage and closed head injury in adults, though early frontal
lobe damage is also associated with poor empathic and social development.
Although alterations in empathy have been studied in only a handful of neurologic
samples thus far, it may be an important outcome variable of brain injury,
particularly in patients' adjustment to family, community and vocational
settings. Treatment possibilities are presented, though more comprehensive
research is needed.
PMID- 9635469
TI - Central pathway of taste: clinical and MRI study.
AB - We present 3 cases of hemiageusia due to focal ischemic lesions in the brainstem.
Clinical presentation with discrete localization of these lesions suggests that
the central taste pathway in humans projects ipsilaterally from the solitary
nucleus up to the level of the upper pontine or lower midbrain before
decussation. Associated partial sensory disturbance of the face or limb with lack
of evidence of medial lemniscus decussation at the upper brainstem suggests that
the medial lemniscus may not directly convey taste sensation.
PMID- 9635470
TI - Isolated so-called apraxia of eyelid opening: report of 10 cases and a review of
the literature.
AB - So-called apraxia of eyelid opening (scAEO) has been described chiefly in the
context of extrapyramidal disorders. We described 10 new patients with scAEO
developing in the absence of any other CNS sign and reviewed the 11 cases with
isolated scAEO reported in the literature. Combining our patients and those from
the literature, peak age at onset was in the 6th decade and there was a female
preponderance of 2:1. The characteristic inability to initiate lid elevation was
frequently associated with failure to sustain lid elevation, thus suggesting that
eyelid motor control may be abnormal in isolated scAEO. Antecedent events
included ocular signs and symptoms consistent with diseases of eyes or face (4
cases in our series and 2 in the literature), chronic treatment with flunarizine
(1 case), and family history of dystonia (1 case). Flunarizine discontinuation
led to sustained remission of the eyelid disturbance. Overall, these clues
suggest the involvement of the extrapyramidal system in the pathophysiology of
isolated scAEO. Familial clustering of isolated scAEO in one of our patients may
be in favor of a genetic contribution. In our series, botulinum toxin
administration close to the pretarsal part of the orbicularis oculi muscle
significantly improved scAEO in 8/10 cases, whereas orbital/preseptal injection
had no effect. We conclude that the term 'apraxia' may not be the correct
descriptive term even when the eyelid disturbance occurs without any other CNS
disease.
PMID- 9635471
TI - Pure sensory syndromes in thalamic stroke.
AB - We studied 25 patients with an acute thalamic stroke (infarct or hemorrhage) on
CT or MRI scan and sensory dysfunction, among the 3,628 patients with first-time
stroke included in the Lausanne Stroke Registry. Twelve patients had a right
sided infarct, 11 a left-sided infarct, and 2 a left-sided thalamic hemorrhage.
Sensory symptoms or signs were the only clinical abnormality. The presumed causes
of stroke were small artery disease in 21 patients including both cases of
hemorrhage, emboligenic heart disease in 2, while the etiology of ischemic stroke
was undetermined in 2 patients. Nine patients had a loss of all modalities of
sensation with faciobrachiocrural distribution, 5 patients suffered dissociated
sensory loss with faciobrachiocrural distribution and 11 patients showed a
dissociated involvement of sensation with a partial distribution pattern. The
inferolateral region (thalamogeniculate arteries) was involved in all patients.
Six patients complained of pain and/or dysesthesias during the stroke; 5 of them
had involvement of the nucleus ventrocaudalis (in 3 with damage to the nucleus
ventro-oralis intermedius, and in one to the pulvinar) and 1 patient had
involvement of the nucleus ventro-oralis intermedius. Eighteen patients
complained of paresthesias in the contralateral part of the body; 16 of them had
involvement of the nucleus ventrocaudalis (in 4 with damage to the nucleus ventro
oralis intermedius, in 1 with damage to the nucleus ventro-oralis intermedius,
and nucleus ventro-oralis externus, and in one with damage to the nucleus
parvocellularis and pulvinar). Four patients developed delayed pain and/or
dysesthesias; all of them had involvement of the nucleus ventrocaudalis (in 1
with damage to the nucleus parvocellularis and pulvinar). Time lag from stroke
onset to developing pain ranged from 2 to 15 days (mean 10.5 days). One patient
with dissociated involvement of sensation with a partial distribution pattern had
paresthesias and dissociated hemisensory loss involving position sense without
pain and temperature sensations. This patient had involvement of the
posterolateral part of the nucleus ventrocaudalis. In conclusion, sensory
dysfunction and delayed pain are more often found in thalamic lesions that
involve the nucleus ventrocaudalis, and nucleus ventro-oralis intermedius.
Restricted sensory abnormalities correlate with very small lesions located in
critical areas within these nuclei.
PMID- 9635472
TI - Muscle weakness in Parkinson's disease: isokinetic study of the lower limbs.
AB - Isokinetic strength of knee extension and flexion was measured at two speeds of
movement in 23 patients with Parkinson's disease, to clarify whether muscle
weakness is inherent to the disease. To counteract normal variation among
subjects, we selected patients with symptoms completely or largely confined to
one side and compared sides for each patient. The affected side was weaker than
the other in both slow and fast movements early in the disease. In more advanced
disease, the difference between sides diminished at the slow speed but remained
significant at the faster speed. These observations suggest that weakness is
inherent to Parkinson's disease and influenced by movement speed.
PMID- 9635473
TI - Thiopental in CSF and serum correlates with prolonged loss of cortical activity.
AB - Barbiturate coma is initiated in brain-injured patients whenever elevated
intracranial pressure remains unresponsive to other therapeutical strategies.
However, barbiturates alter cortical activity resulting in difficulties in
clinical evaluation. Therefore, we investigated the impact of long-term
thiopental administration on responsiveness to exteroceptive stimuli in relation
to pharmacokinetics of thiopental in CSF and serum. Long-term infusion increases
thiopental levels which remain elevated for 6 and 9 days in CSF and serum,
respectively, after termination of its administration. Prolonged unresponsiveness
to exteroceptive stimuli correlates with persisting thiopental in CSF and serum.
Thus, quantitative analysis of thiopental in serum becomes indispensable in
predicting the length of drug-induced neurological impairment and in avoiding
misinterpretation of the neurological status.
PMID- 9635474
TI - Apolipoprotein E polymorphism in Alzheimer's disease: a comparative study of two
research populations from Spain and the United States.
AB - We examined the distribution of the apolipoprotein E (APOE) polymorphism in two
Caucasian populations of Alzheimer's disease (AD) patients referred to dementia
clinics; one in Gerona, Spain (66 AD patients, 49 controls), and the other in
Pittsburgh, Pa., USA (209 AD patients, 58 controls). The presence of the APOE*4
allele was a significant risk for developing AD in both cohorts: Gerona (odds
ratio = 2.34, CI: 1.03-5.55) and Pittsburgh (odds ratio = 3.64, CI: 1.78-7.69).
The proportion of AD with the APOE*4 allele was greater in the Pittsburgh cohort
than in the Gerona cohort (p = 0.02). However, no statistical difference was
noted between the two populations in nondemented controls (p = 0.41). These data
emphasize the importance of geographical and ethnic variations in the study of
APOE genotypes.
PMID- 9635475
TI - Prevalence of dementia of Alzheimer type and apolipoprotein E phenotypes in aged
patients with Down's syndrome.
AB - We investigated the exact prevalence of dementia of Alzheimer type (DAT) and
apolipoprotein E (ApoE) phenotypes in 106 Japanese Down's syndrome (DS) patients.
Among these patients 16 were diagnosed as having DAT. The prevalence of DAT was
0% in the 30- to 39-year-old group, 16% in the 40- to 49-year-old group, and 38%
in those over 50 years old. The frequency of the epsilon4 allele in DS patients
with DAT was 18.8%, which was considerably higher than that of nondemented DS
patients (4.5%) and Japanese nondemented controls (6.7%). Especially, the
frequency of the epsilon4 allele in DS patients who developed DAT under 50 years
was significantly higher (28.6%). DS patients certainly develop DAT at earlier
ages but the prevalence of DAT in each group of patients was lower than
previously recognized. It is very likely that the ApoE epsilon4 is a risk factor
for DAT even in DS patients with a genetic predisposition to Alzheimer's disease.
PMID- 9635476
TI - Increased plasma concentration of atrial natriuretic hormone in myotonic
dystrophy.
AB - Atrial natriuretic hormone (ANH) concentrations were measured in 16 patients
affected with myotonic dystrophy (MyD) undergoing 24-hour Holter ECG and in 15
age-matched normal subjects. Although the MyD patients did not show overt left
ventricular function impairment, their plasma ANH levels were found to be higher
(183.76 +/- 113.25 pg/ml) compared to those of the control subjects (39.73 +/-
9.95 pg/ml, p < 0.001). Nine patients with arrhythmias and some echocardiographic
alterations formed subgroup A. Seven patients without cardiac alterations formed
subgroup B. No significant difference in ANH emerged between the two subgroups.
This evidence suggests that high plasma ANH levels in MyD cannot always be
related to overt or latent heart failure and to arrhythmias.
PMID- 9635477
TI - Reversible adverse effects on the CNS induced by histamine H2 receptor
antagonists.
PMID- 9635478
TI - Dysthyroid ophthalmopathy misinterpreted as ocular myositis.
PMID- 9635479
TI - A retrospective study of infantile hydrocephalus observed in Benin.
PMID- 9635480
TI - Cerebral venous thrombosis and estrogen-progesterone therapy.
PMID- 9635481
TI - A case of carbamazepine-induced lymphadenopathy resembling Kikuchi disease.
PMID- 9635482
TI - Successful treatment of focal epilepsy by fractionated stereotactic radiotherapy.
PMID- 9635483
TI - A localized postoperative cervical syrinx revealed by orthostatic hypotension.
PMID- 9635484
TI - Use of aquatic invertebrates in genotoxicological studies.
PMID- 9635485
TI - Mutagen content and metabolic activation of promutagens by molluscs as biomarkers
of marine pollution.
AB - Organisms combat pollutants by inducing biotransformation pathways, which can be
used for biomonitoring. Several parameters--biomarkers--change in stressed
organisms or populations at different organisation levels. Molecular or cellular
biomarkers are early-warning indicators of pollution. Xenobiotics are first
biotransformed by phase I enzymes and then conjugated with endogenous metabolites
by phase II enzymes. Many organic xenobiotics are initially biotransformed by
cytochrome P4501A1; in mammals, it is induced by pollutants via Ah receptor,
although in marine invertebrates, its inducibility is much more equivocal.
Metallothioneins are small Cys-rich proteins which bind transition metals; they
detoxicate pollutant metals and are clearly induced in metal-exposed marine
invertebrates. Some pollutants are genotoxins or can be converted into them.
Determination of mutagens in bivalve molluscs following extraction with solvents
and assay of mutagenicity with bacterial tests is a useful biomarker for marine
pollution. While some pollutants are directly mutagenic, others are only
mutagenic after they are activated to mutagenic derivatives by monooxygenases or
conjugative enzymes. Many of these catalysts are induced by xenobiotics; thus,
increased activation of known promutagens can be used as biomarker of
environmental pollution. Bioactivation of promutagens requires the simultaneous
action of different pathways, thus, reproducing more closely the in vivo
situation than the specific assay of individual biotransforming enzymes. Study of
molluscs with different pollution levels indicates that polluted animals have
higher capacity to activate 2-aminoanthracene and contain more apolar mutagens
than those from reference areas.
PMID- 9635486
TI - Tissue dose, DNA adducts, oxidative DNA damage and CYP1A-immunopositive proteins
in mussels exposed to waterborne benzo[a]pyrene.
AB - A collaborative study was performed on Mediterranean mussels (Mytilus
galloprovincialis) exposed to a wide dose-range (0.5-1000 ppb) of benzo[a]pyrene
(B[a]P). We selected this model polycyclic aromatic hydrocarbon in order to
confirm the formation of a specific DNA adduct, previously detected in gill DNA,
and to clarify the in vivo effects of this mutagenic chemical requiring host
metabolism in mussels. B[a]P concentration reached consistently higher values in
the digestive gland than in other analyzed tissues of mussels exposed to B[a]P
for 2 or 3 days. With the exception of some values at 1000 ppb of B[a]P. DNA
adduct levels increased significantly with the dose in gills and digestive gland
and ranged from 0.054 to 0.789 adducts per 10(8) nucleotides (mean values per
dose-point). Conversely, more complex dose-response relationships were found by
detecting in parallel the levels of an oxidative DNA lesion (8-OHdG) and of CYP1A
immunopositive proteins (the latter measured in the digestive gland only).
Overall, the formation of DNA adducts, the evidence of oxidative DNA damage, and
changes in CYP1A-immunopositive protein levels support the hypothesis that B[a]P
can induce DNA damage in mussels through a number of different molecular
mechanisms.
PMID- 9635487
TI - The analysis of DNA adduct formation, removal and persistence in the common
mussel Mytilus edulis exposed to 4-nitroquinoline 1-oxide.
AB - 32P-postlabelling was used for the detailed analysis of 4-nitroquinoline 1-oxide
(4-NQO) induced DNA adduct formation, removal and persistence in the marine
shellfish Mytilus spp. The results had a number of important implications
concerning the use of such DNA adducts as dosimeters of environmental genotoxin
exposures. Our studies indicated that the maintenance of the Mytilus specimens
under controlled laboratory conditions can result in the induction of 'stress
related adducts' seemingly related to the nature of the experimental set-up. The
studies also indicated that the absorption and activation of genotoxins in this
species appear to affect the rate of adduct formation, and that the maximum
levels of adducts may not necessarily be induced immediately after the cessation
of a genotoxin exposure. In addition, Mytilus specimens were shown to possess a
significant capacity to remove these genotoxin-induced DNA adducts. The removal
of these adducts appeared to be biphasic in nature, with the rapid removal of a
large proportion of adducts occurring within 48 h of the cessation of the
exposure, followed by a slow rate of adduct removal over the remaining period of
the studies. Despite the relatively efficient removal of the majority of these
genotoxin-induced DNA adducts, a proportion remained up to 56 days after the
initial exposure. The persistence of these genotoxin-DNA adducts, combined with
the information on the rates of adduct removal, indicated that under well-defined
conditions, such adducts could serve as suitable biomarkers of environmental
contamination.
PMID- 9635488
TI - The chemosensitizers of multixenobiotic resistance mechanism in aquatic
invertebrates: a new class of pollutants.
AB - Mechanism of multixenobiotic resistance (MXR), identical to multidrug resistance
(MDR) in tumor cells, has been found in aquatic invertebrates. The presence of
this ATP-dependent membrane P-glycoprotein (Pgp) pump was confirmed by
biochemical ('binding'), molecular (immunohistochemical, Western, Northern),
physiological (verapamil-sensitivity) and toxicological (modulation of toxicity)
methods. The inducibility of MXR in the presence of xenobiotics and its wide
taxonomic distribution suggests its role as a general biological defense
mechanism that rescues organisms by pumping potentially toxic xenobiotics out of
the cells. Some xenobiotics, the chemosensitizers, can inhibit this defense
mechanism. The presence of these MXR-inhibitors has important implications on
environmental parameters like exposure, uptake, internal dose, bioaccumulation,
response, synergism and toxicity. Such MXR-inhibitors, for example, enhance the
accumulation of carcinogenic aromatic amines in mussel, with subsequent
enhancement in production of their mutagenic metabolites, in induction of single
strand breaks in DNA, and in induction of DNA-adducts. The property to inhibit
defense mechanism of organisms classifies MXR-inhibitors among top-hazardous
environmental chemicals. Therefore, we measured the concentration of
chemosensitizers in water concentrates or sediment extracts as their potential to
modulate the accumulation of fluorescent dyes in a cell-culture of NIH 3T3 mouse
fibroblasts stable transfected with human MDR1 gene, or as the potential of
native waters to decrease the efflux-rate of Rhodamine B from gills of mussels.
We found significantly higher concentrations of MXR-inhibitors in samples from
polluted marine sites or from polluted rivers than in samples from corresponding
unpolluted sites. These concentrations were able to enhance the accumulation of
fluorescent dyes or carcinogenic aromatic amines in clams, mussels, snails and
sponges exposed to these xenobiotics, demonstrating the ecotoxicological
relevance of MXR-inhibitors present in polluted waters.
PMID- 9635489
TI - Transgenic nematodes as biomonitors of microwave-induced stress.
AB - Transgenic nematodes (Caenorhabditis elegans strain PC72), carrying a stress
inducible reporter gene (Escherichia coli beta-galactosidase) under the control
of a C. elegans hsp16 heat-shock promoter, have been used to monitor toxicant
responses both in water and soil. Because these transgenic nematodes respond both
to heat and toxic chemicals by synthesising an easily detectable reporter
product, they afford a useful preliminary screen for stress responses (whether
thermal or non-thermal) induced by microwave radiation or other electromagnetic
fields. We have used a transverse electromagnetic (TEM) cell fed from one end by
a source and terminated at the other end by a matched load. Most studies were
conducted using a frequency of 750 MHz, at a nominal power setting of 27 dBm. The
TEM cell was held in an incubator at 25 degrees C inside a shielded room;
corresponding controls were shielded and placed in the same 25 degrees C
incubator; additional baseline controls were held at 15 degrees C (worm growth
temperature). Stress responses were measured in terms of beta-galactosidase
(reporter) induction above control levels. The time-course of response to
continuous microwave radiation showed significant differences from 25 degrees C
controls both at 2 and 16 h, but not at 4 or 8 h. Using a 5 x 5 multiwell plate
array exposed for 2 h, the 25 microwaved samples showed highly significant
responses compared with a similar control array. The wells most strongly affected
were those in the rows closest to the source, whereas the most distant row did
not rise above control levels, suggesting a shadow effect. These differential
responses are difficult to reconcile with general heating effects, although
localised power absorption affords a possible explanation. Experiments in which
the frequency and/or power settings were varied suggested a greater response at
21 than at 27 dBm, both at 750 and 300 MHz, although extremely variable responses
were observed at 24 dBm and 750 MHz. Thus, lower power levels tended, if
anything, to induce larger responses (with the above-mentioned exception), which
is opposite to the trend anticipated for any simple heating effect. These results
are reproducible and data acquisition is both rapid and simple. The evidence
accrued to date suggests that microwave radiation causes measurable stress to
transgenic nematodes, presumably reflecting increased levels of protein damage
within cells (the common signal thought to trigger hsp gene induction). The
response levels observed are comparable to those observed with moderate
concentrations (ppm) of metal ions such as Zn2+ and Cu2+. We conclude that this
approach deserves further and more detailed investigation, but that it has
already demonstrated clear biological effects of microwave radiation in terms of
the activation of cellular stress responses (hsp gene induction).
PMID- 9635490
TI - DNA damage in mussels at sites in San Diego Bay.
AB - Identification and assessment of introduced and other toxicants is crucial to any
comprehensive study of contaminants within the marine environment. The
relationship between DNA single-strand breaks and the exposure of marine
organisms to environmental contaminants was examined at sites in San Diego Bay,
CA. A comprehensive assessment of the extent and consequences of marine
environmental contamination in the area of Naval Station San Diego was conducted
in the summer of 1995. The study addressed contamination sources, distributions,
concentrations, transport, sediment-water exchange, biological effects, and
degradation. The biological effects portion of the study (this paper) included
contaminant bioaccumulation, organismal growth, and the determination of DNA
single-strand breaks using the Comet assay. DNA damage was determined in
hemocytes collected from deployed and resident mussels, Mytilus edulis, at six
stations in and around the Naval Station San Diego. Deployed mussels were exposed
on station for approximately 30 days in plastic mesh bags, placed 1 m above the
bottom. Hemocyte samples were collected on days 0, 12, and 32. It was found that
stations exhibiting the extremes of contaminant exposure, both highest and lowest
concentrations, were easily identified using growth and DNA damage measurements.
Sediment chemistry and bioaccumulation data indicated, Hg, Cu, and Zn, to be the
most notable contaminants. The Comet assay, and in particular germ cell DNA
damage determinations, were found to respond rapidly to station contaminants.
Results from this study and an earlier 1993 study suggest that the non-sediment
associated effects observed at one station may have been the result of the
photoactivation of accumulated PAHs.
PMID- 9635491
TI - Evaluation of the comet assay as a method for the detection of DNA damage in the
cells of a marine invertebrate, Mytilus edulis L. (Mollusca: Pelecypoda).
AB - The potential application of the comet assay for monitoring the effect of DNA
damaging agents on the marine mussel, Mytilus edulis (an important pollution
indicator organism), was explored. A detailed investigation of the baseline
levels of single-strand breaks in isolated gill cells, and how they were affected
by age/size of animal, time since collection, feeding regime, in vivo vs. in
vitro exposure conditions, and by antioxidant supplementation was undertaken. The
level of cometing in untreated controls was found to be highly variable over time
(fluctuations between low and very high DNA damage occurred over just 14 days
post collection). No difference was observed between age/size and feeding regime
of the animals. On exposure to 0, 100, 500 and 1000 microM H2O2, it was observed
that the in vitro exposure produced a markedly more homogeneous dose response
compared to the in vivo studies (where gill cells were exposed as a tissue). An
important finding of our research was the effect of prior supplementation of the
animals' diet with 1 mg/ml alpha-tocopherol acetate (vitamin E compound), which
resulted in a marked reduction in the levels of DNA damage expressed by the
negative controls, without influencing the actual response to H2O2 (0, 5, 25, and
100 microM) and N-nitrosodimethylamine, NDMA (0, 5, 25, and 100 mM). The effect
of vitamin E supplementation was to increase the sensitivity of the comet assay
at the lower end of the dose range. This study demonstrated the potential
application of the comet assay to the gill cells of the mussel, M. edulis.
Although preliminary findings suggest that antioxidant supplementation can
improve the sensitivity of the assay by lowering the baseline damage in untreated
animals, our conclusion is that the assay has more potential for use in an in
vitro context for the screening of agents destined for release or disposal into
the marine environment.
PMID- 9635492
TI - Assessment of developmental effects, cytotoxicity and genotoxicity in the marine
polychaete (Platynereis dumerilii) exposed to disinfected municipal sewage
effluent.
AB - While sodium hypochlorite is widely used as a disinfectant for municipal sewage
effluents and power station cooling waters discharged into coastal environments,
there is limited information on the potential in vivo genotoxicity of such
disinfection procedures to marine organisms. Using a recently developed test
system based on the marine polychaete Platynereis dumerilii, we have evaluated
impacts based on embryo-larval development, cytotoxicity and genotoxicity
following exposure to disinfected settled (primary) effluent from a municipal
sewage treatment works (STW). Sewage samples were collected from Newton Abbot
STW, Devon, UK and then disinfected with sodium hypochlorite based on standard
operational procedures. Exposure of polychaetes to dilutions of disinfected
sewage in seawater (20 +/- 1 degree C) led to a marked reduction in normal embryo
larval development (7 h EC50 from 0.57-1.88% (v/v), n = 4), with a simultaneous
increase in cytotoxicity. Following the calculation of the Maximum Tolerated Dose
(MTD), based on developmental and cytotoxic effects, the organisms were also
analysed for the induction of chromosomal aberrations. This investigation
demonstrated the absence of genotoxicity in polychaetes exposed in vivo to sewage
disinfected with sodium hypochlorite. These observations extend our previously
published studies in which polychaetes exposed to non-disinfected sewage, while
showing developmental toxicity and cytotoxicity, did not exhibit any evidence of
cytogenetic damage.
PMID- 9635493
TI - The ecotoxicological significance of genotoxicity in marine invertebrates.
AB - Attention is drawn to the goals of genetic ecotoxicology, in particular, the need
to relate genotoxicity in individuals to population and community level
consequences. The evidence for pollutant-induced genotoxicity in marine
invertebrates is reviewed. Neoplasia is apparently rare in marine invertebrates
and only limited evidence is available to suggest that chemical genotoxins act as
causative agents. It is unknown why marine invertebrates exhibit low tumour
incidences and are much more tolerant of ionising radiation than their vertebrate
counterparts. The importance of the genotoxic disease syndrome is highlighted.
Disentangling phenotypic manifestations of genotoxic damage and that due to
direct metabolic toxicity provides a major challenge for the future. Further work
is required to assess the significance of interspecific and interindividual
variability in susceptibility to genotoxicity, especially with regard to the
evolution of resistant populations and communities of marine organisms at
contaminated sites. Only by addressing the issues highlighted above can proper
risk assessments of genotoxic agents be performed to minimise threats to human
and ecosystem health.
PMID- 9635494
TI - Characterization of fibronectin-related substances in normal and passive Heymann
nephritis rats.
AB - The excretion mechanism of fibronectin (FN)-related substances into the urine of
normal and passive Heymann nephritis (PHN) rats was studied using enzyme
immunoassay and immunoblot analysis. In normal rats, a small amount (0.20+/-0.067
microg/d) of FN-related substances, composed of 55- and 65-kDa FN fragments
derived from the central cell-binding (Cell) domain of FN, were constitutively
excreted into the urine. When PHN was induced in rats by the injection of an anti
Fx1A antibody, an increased excretion (4.96+/-3.51 microg/d) of intact FN and
large (Mr > 100-kDa) FN fragments containing the Cell and the other functional
domains were seen. The PHN induction also caused the appearance of a considerable
amount of Cell domain-containing FN fragments in plasma. Both the renal cortex
homogenates of normal and PHN rats were capable of degrading plasma FN to
generate the Cell domain-containing large FN fragments. Degradation of FN by the
renal cortex homogenate was shown to be due to metal and/or thiol proteinase(s).
These results suggest that the PHN-induced urinary excretion of FN fragments may
be due to the degradation of plasma FN by renal proteinases that may be leaked
upon PHN induction.
PMID- 9635495
TI - Low-dose irradiation induces expression of heat shock protein 70 mRNA and thermo-
and radio-resistance in myeloid leukemia cell line.
AB - We examined the effects of in vitro low-dose irradiation on myeloid leukemia
cells (M1 cells) and found that it enhanced the colony-forming ability (CFA) of
M1 cells in semi-solid agar. This enhancement was inhibited by treatment with a
protein synthesis inhibitor, cycloheximide and with an RNA synthesis inhibitor,
actinomycin D, after irradiation. These findings suggested that low-dose
irradiation induced the synthesis of some proteins which were attributed to the
enhancement of CFA. Since we expected that one species of these proteins were
heat shock proteins (hsps), we attempted to detect the hsp70 family by the
Western blotting method and inducible hsp70 mRNA by the RT-PCR method. Low-dose
irradiation induced the expression of hsp70 mRNA, whereas the enhancement of
hsp70 (an inducible isoform) and hsc70 (a constitutively expressed isoform)
expression could not be found. Furthermore, the M1 cells showed thermoresistance
1 h after low-dose pre-irradiation, and also showed radioresistance 4 h after
irradiation. This time difference after pre-irradiation might be attributed to
the different species of proteins in showing resistance to lethal stress.
Therefore, some proteins other than hsp70 were believed to be concerned with the
augmentation of CFA and the induction of thermo- and radio-resistance.
PMID- 9635496
TI - Inhibitory effect of regucalcin on Ca2+/calmodulin-dependent phosphatase activity
in rat renal cortex cytosol.
AB - The effect of regucalcin, a Ca2+-binding protein, on Ca2+/calmodulin-dependent
phosphatase activity in rat renal cortex cytosol was investigated. The addition
of Ca2+/calmodulin in the enzyme reaction mixture caused a significant increase
in the dephosphorylation of p-nitrophenylphosphate and phosphotyrosine used as
the substrate for phosphatase in rat renal cortex cytosol. The presence of
regucalcin (10(-6) M) in the enzyme reaction mixture caused a complete inhibition
of Ca2+/calmodulin-dependent phosphatase activity in renal cortex cytosol. A half
maximum effect of regucalcin inhibition was seen at 10(-8) M concentration.
Moreover, phosphatase activity of purified calcineurin was significantly enhanced
by the addition of Ca2+/calmodulin. This enhancement was completely inhibited by
the presence of regucalcin (10(-7) M). The inhibitory effect of regucalcin was
not weakened by increasing concentrations of CaCl2 (10(-6) to 10(-4) M). The
present results suggest that regucalcin can inhibit Ca2+/calmodulin-dependent
phosphatase activity in rat renal cortex.
PMID- 9635497
TI - An ergosterol peroxide, a natural product that selectively enhances the
inhibitory effect of linoleic acid on DNA polymerase beta.
AB - As described previously (Mizushina Y., Tanaka N., Yagi H., Kurosawa T., Onoue M.,
Seto H., Horie T., Aoyagi N., Yamaoka M., Matsukage A., Yoshida S., and Sakaguchi
K., Biochim. Biophys. Acta, 1308, 256-262, 1996), linoleic acid (LA) inhibits the
activities of mammalian DNA polymerases. We found a natural product from a
basidiomycete, Ganoderma lucidum, that enhances this effect of LA in a special
manner. The structure was identified to be an ergosterol peroxide, 5,8-epidioxy
5alpha,8alpha-ergosta-6,22E-dien -3beta-ol by spectroscopic analyses. The
ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus
DNA polymerase alpha (pol. alpha) or rat DNA polymerase beta (pol. beta).
However, when EPO at 0.25 mM was present, 10 microM or less of LA almost
completely inhibited the pol. beta activity, while almost complete inhibition by
LA itself was achieved at 80 microM or higher. Interestingly, under the same
conditions, EPO did not affect the LA-effect on pol. alpha. The action mode of
the EPO was discussed.
PMID- 9635498
TI - Effects of YJA20379-4 on gastric secretion, Helicobacter pylori growth and
various gastric and duodenal lesions in rats.
AB - Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton
pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric
acid secretion, and gastro-duodenal lesions, were examined in comparison with
those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a
concentration-dependent manner and the inhibitory effect was increased under a
weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4,
respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol
(DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity
determined by the agar dilution method. The value of minimum inhibitory
concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than
that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric
acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg).
In experimental ulcer models, YJA20379-4 administered by the oral route dose
dependently prevented the development of gastro-duodenal lesions in rats.
Moreover, repeated administration of YJA20379-4 promoted the healing of gastric
ulcers induced by acetic acid. On the basis of the data obtained, it is suggested
that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of
antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H.
pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might
prove to be a beneficial therapy for gastritis and peptic ulcer diseases.
PMID- 9635499
TI - Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial
agent in intravenous use. I. Effects of doses and infusion rate on blood
pressure, heart rate and plasma histamine concentration.
AB - T-3762, a newly developed fluoroquinolone antimicrobial agent, ciprofloxacin
(CPFX) and ofloxacin (OFLX) were administered intravenously to anesthetized dogs
by intravenous infusion, and blood pressure, heart rate and plasma histamine
concentrations were monitored. T-3762 decreased blood pressure by 12.0%, without
alterations in heart rate and plasma histamine concentration, only when infused
at 150 mg/min. CPFX and OFLX both produced a rapid decrease in blood pressure in
a dose-related manner, with an accompanying decrease in heart rate, but to a
lesser extent. After infusion at 150 mg/min, CPFX caused death in 2 animals
within a few minutes, while OFLX produced maximum decreases in blood pressure and
heart rate, by 69.0% and 26.4%, respectively. The infusion of these 2 agents
resulted in dose-related increases in plasma histamine concentrations parallel to
the decreases in blood pressure: the maximum, attained with CPFX at 50 mg/min and
OFLX at 150 mg/min, were 379.2 and 167.8 ng/ml, respectively. For CPFX and OFLX,
the relationship between the maximum levels of decreased blood pressure and
increased histamine concentration in plasma was highly significant. The
hypotension induced by CPFX was efficiently reduced by the pretreatment of
animals with antihistamines. The results from this study suggest that hypotension
induced in dogs following the intravenous infusion of fluoroquinolone
antimicrobial agents may be dependent on their ability to cause histamine release
from cells and tissues, and indicates that T-3762 is devoid of this ability in
comparison to CPFX and OFLX.
PMID- 9635500
TI - Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial
agent in intravenous use. II. Dermovascular permeability-increasing effect and
action on peritoneal mast cells.
AB - To predict the actions of T-3762, a newly developed fluoroquinolone antimicrobial
agent, as well as ciprofloxacin (CPFX) and ofloxacin (OFLX), on injection sites
when dosed parenterally, their ability to increase cutaneous vascular
permeability in dogs and to release histamine from rat peritoneal mast cells was
examined. CPFX and OFLX increased cutaneous vascular permeability in
concentrations ranging from 16 to 32 microg/ml, while T-3762 was inactive at 2000
microg/ml. The vascular permeability-increasing activities of these drugs were
inhibited efficiently by pretreatment with a combined dose of diphenhydramine and
cimetidine. CPFX induced histamine release from rat mast cells in a dose
dependent manner, whereas T-3762 was ineffective. Therefore, it is concluded that
fluoroquinolone antimicrobial agents may have the ability to cause an increase in
cutaneous vascular permeability by releasing histamine from mast cells at the
injection site when administered parenterally, and that T-3762 has minimum
activity among the agents tested in this study.
PMID- 9635501
TI - Twist form of teleocidin derivatives is active in in vivo tumor promotion by (-)
benzolactam-V8-310.
AB - Teleocidin derivatives and the core structure, (-)-indolactam-V ((-)-IL-V), adopt
two conformations in solution, the "twist" and the "sofa" forms. (-)-Benzolactam
V8-310 ((-)-BL-V8-310), which specifically adopts the twist form in solution, has
been reported to have a significant effect on HL-60 cells and protein kinase C
affinity. In this paper, we describe the biological activity with regard to tumor
promotion on mouse skin and the wide variety of biological activity of (-)-BL-V8
310 and its derivatives. In both twist and sofa forms (-)-BL-V8-310 inhibited
specific 3H-12-O-tetradecanoylphorbol-13-acetate (TPA) binding to a particulate
fraction of mouse skin more strongly than (-)-IL-V. The doses for 50% inhibition
(IC50) of (-)-IL-V, (-)-BL-V8-310, and teleocidin B-4 were 1000, 400 and 12 nM,
respectively. As for the induction of tumor necrosis factor-alpha (TNF-alpha)
release into the medium from HL-60 cells, the EC200 values, which are the
concentrations of the compound required to achieve 200 pg/ml TNF-alpha in the
medium, were 1700, 500 and 19 nM for (-)-IL-V, (-)-BL-V8-310 and teleocidin B-4,
respectively. The same amounts (5.5 nmol per application) of (-)-BL-V8-310 and
teleocidin B-4, induced tumors on mouse skin initiated with 7,12
dimethylbenz(a)anthracene (DMBA) in 13.3% and 86.7% of tumor-bearing mice,
respectively, in week 20. These results confirmed that the twist form of
teleocidin derivatives is the active form as far as the induction of biological
activity is concerned. Also (-)-BL-V8-310 is a new synthetic tumor promoter
designed from data obtained using the receptor cavity model of TPA-type tumor
promoters.
PMID- 9635502
TI - Antihypertensive effect of sesamin. III. Protection against development and
maintenance of hypertension in stroke-prone spontaneously hypertensive rats.
AB - The antihypertensive effect of sesamin, a lignan from sesame oil, was examined
using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats
(SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group
and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking
water. Each group was further divided into two groups: normal-diet group and
sesamin-diet group. Systolic blood pressure of all animals was monitored once
weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal
damage were evaluated. In the salt-loaded group, sesamin feeding significantly
suppressed the development of hypertension, and efficient suppression was
maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old).
The left ventricle plus septum weight-to-body weight ratio was slightly but
significantly lowered by sesamin feeding. When the degree of vascular hypertrophy
of the aorta and superior mesenteric artery was histochemically evaluated, wall
thickness and wall area of these vessels were significantly decreased by the
sesamin feeding. Histological renal damage such as thickening of the tunica
intima and fibrinoid degeneration of the arterial wall were often observed in the
normal-diet group, but this damage was efficiently reduced in the sesamin-fed
animals. On the other hand, in the salt-unloaded group, only a slight and
nonsignificant suppressive effect of sesamin on the development of hypertension
was observed. Although the wall area of the aorta was significantly decreased by
the sesamin feeding, other vascular parameters were not ameliorated. The
incidence of histological renal damage tended to decrease in sesamin-fed animals,
but these alterations were not statistically significant. Thus, sesamin feeding
was much more effective as an antihypertensive regimen in salt-loaded SHRSP than
in unloaded SHRSP, thereby suggesting that sesamin is more useful as a
prophylactic treatment in the malignant status of hypertension and/or
hypertension followed by water and salt retention.
PMID- 9635503
TI - Phylogenetic analysis of Atractylodes plants based on chloroplast trnK sequence.
AB - The phylogenetic relationship of Atractylodes lancea, A. chinensis, A. koreana,
A. ovata and A. japonica were analyzed by comparing the 2.6 kb sequence in a
chloroplast gene trnK encoding tRNALys (UUU). The dried rhizomes of the former
three species have been used as the crude drug "So-jutsu" and those of the latter
two as "Byaku-jutsu" in Chinese and Japanese traditional medicine ("Kampo
medicine"). The trnK phylogenetic tree revealed that A. ovata is an outgroup of
the five Atractylodes species examined and that A. japonica and A. lancea are
most closely related. PCR amplification of trnK with HinfI digestion provided us
with a simple method to distinguish A. ovata from other Atractylodes species at
the molecular level.
PMID- 9635504
TI - Atractylodes lancea autotetraploids induced by colchicine treatment of shoot
cultures.
AB - Two strains of autotetraploid plants of Atractylodes lancea DC. (Compositae) were
raised from the in vitro colchicine-treated shoot cultures, and field trials were
performed to evaluate their growth and the amount of essential oil components in
the rhizome in comparison with the corresponding diploids. The tetraploid plants
had larger leaves than the diploids. One of the selected tetraploid lines had
about 1.5 times as heavy rhizomes as the diploid and contained atractylodin,
hinesol and beta-eudesmol in the rhizome to as great an extent or slightly less
than the diploids. However, the contents of these constituents in the rhizome of
the other tetraploid strain were lower than the diploids. The chloroplast number
per guard cell, stomatal length, and stomatal density of leaf lower epidermis of
the shoot cultures were good indicators for distinguishing tetraploids from
diploids.
PMID- 9635505
TI - Skin penetration enhancing action of cis-unsaturated fatty acids with omega-9,
and omega-12-chain lengths.
AB - The skin penetrative action of high purity cis-omega-12-octadecenoic acid
(petroselinic acid, HP-PSA) on rat skin was compared with that of high purity cis
omega-9-octadecenoic acid (oleic acid, HP-OA), following treatment of rat intact
skin surface with either 0.05 M HP-PSA or HP-OA in propylene glycol (PG), using
Fourier transform/attenuated total reflection (FT-IR/ATR) analysis. Both HP-PSA
and HP-OA disordered the lipid structures of the stratum corneum region to a
similar extent. Removal of the extractable lipids of the stratum corneum region
was marked with HP-PSA/PG but was very slight upon HP-OA/PG treatment. The
spectra of the amide II region which originated from proteins suggests that HP
PSA/PG more rapidly disordered the protein structures of both the stratum corneum
and the dermis than HP-OA/PG. However, the extent of disordering of the protein
structures was presumed to be similar between these two skin penetration
enhancers at the maximum level. Enhancement of PG flux in the dermis showed
strong positive correlation with the degree of dermis-disordering action of HP
PSA/PG and HP-OA/PG. These results demonstrate that HP-PSA, which has a double
bond at an even numbered position (omega-12), more rapidly affects the
perturbation of the structures of both the stratum corneum and the dermis than HP
OA, which has the double bond at an odd numbered position (omega-9). Differences
in the physicochemical properties of HP-PSA and HP-OA which originate from
differences in the double bond position most likely determine the efficacy of
these compounds as skin penetration enhancers.
PMID- 9635506
TI - Control of plasma cholesterol-lowering action of probucol with various lipid
carrier systems.
AB - In order to explore the relationship between the pharmacokinetic properties and
pharmacological actions of lipophilic drugs injected with lipid carrier systems,
probucol was selected as a model drug with high lipophilicity, and the effect of
disposition control on cholesterol-lowering activities was evaluated. Both large
emulsion, with mean diameter of 280 nm, and long-circulating type small emulsion
containing egg sphingomyelin with mean diameter of 100 nm, showed stable
incorporation of probucol. The former produced rapid accumulation of probucol in
the liver, while the latter demonstrated prolonged systemic circulation and
gradual hepatic uptake. On the other hand, injection of a micellar solution with
HCO-60 (polyoxyethylene hydrogenated castor oil) showed a rapid decrease in
plasma concentration and a high hepatic uptake of probucol, similar to injections
with serum, suggesting the rapid release of the drug from the micelles. However,
probucol in a micellar solution showed higher cholesterol-lowering action than
that in emulsion formulations. These results suggested that the pharmacological
action of probucol in the liver might be affected by the uptake mode and
sequential disposition in the organ, depending on the drug retention properties
of the lipid carrier particles.
PMID- 9635507
TI - Studies on the antiviral mechanisms of protein kinase inhibitors K-252a and
KT5926 against the replication of vesicular stomatitis virus.
AB - We investigated the antiviral mechanisms of K-252a, a broad non-specific protein
kinase inhibitor which was isolated from Nocardiopsis sp. and its derivative
(KT5926), against vesicular stomatitis virus (VSV) replication in BHK-21 cells.
Although K-252a (5 microM) and KT5926 (15 microM) similarly suppressed the viral
primary and secondary transcriptions and genomic RNA synthesis in vivo, the
inhibitory mechanisms did not seem to be the same; phosphorylation of the viral
NS protein was suppressed by K-252a, which might account for the decreased viral
RNA synthesis caused by K-252a. On the other hand, KT5926, being known to
preferentially inhibit myosin light chain kinase (MLCK), had little effect on NS
protein phosphorylation. Cellular casein kinase II, which is believed to be
involved in the phosphorylation of the N-terminal side (domain I) of NS protein,
was not inhibited at all by KT5926 even at 15 microM under in vitro assay
conditions, and was only weakly inhibited by K-252a at 1 to 10 microM. Neither
inhibitor seemed to directly affect viral protein synthesis, but affected it
indirectly as a secondary effect of reduced viral RNA synthesis. These results
suggest that both the KT5926-sensitive and the KT5926-resistant but K-252a
sensitive functions are involved in the essential processes of viral RNA
synthesis. The KT5926-sensitive function(s) might not be involved in the NS
protein phosphorylation, but may participate in some other way in the process of
virus replication. On the other hand, the KT5926-resistant, K-252a-sensitive
function(s) are probably involved in NS protein phosphorylation. The possible
nature of those functions is discussed.
PMID- 9635508
TI - Immunocytochemical localization of salivary peptide P-C in human submandibular
gland.
AB - Human saliva contains a proline-rich polypeptide, salivary peptide P-C, which
potentiates insulin release and reduces glucagon release from perfused rat
pancreas to decrease blood glucose level. To elucidate the process of secretion
into humoral fluid of this peptide morphologically, we investigated
ultrastructural localization of P-C in human submandibular gland by immunogold
technique with anti-peptide P-C whose specificity to P-C was confirmed by
immunoblotting. The labeling with gold particles which represents the
distribution of P-C-like-immunoreactivity (P-C-LI) was detected in the secretory
granules and rough endoplasmic reticula of the acinar serous cells and in few
mucosa cells. P-C-LI was also observed in the lumen of striated duct but not
intracellularly in the ductal cells themselves, indicating that P-C is not
probably reabsorbed there. These results suggest that salivary peptide P-C is
present in acinar serous cells, is secreted into the oral cavity, and may be
reabsorbed through the digestive tract to modulate the blood glucose level after
feeding.
PMID- 9635509
TI - Synthesis of a biologically active fluorescent derivative of GM1, a main Ginseng
saponin metabolite formed by intestinal bacteria.
AB - A fluorescent derivative of GM1 [20-O-beta-D-glucopyranosyl-20(S)
protopanaxadiol], a main Ginseng saponin metabolite formed by intestinal
bacteria, was obtained from the condensation of its trisnor-aldehyde derivative
with dansyl hydrazine. The dansylated GM1 fluoresced strongly and showed almost
the same properties as its parent compound in lipophilicity and biological
activities, so this fluorescent compound might provide an insight into the
mechanism of pharmacological activities of GM1.
PMID- 9635510
TI - Enhancement of the vanadate-stimulated release of lipoprotein lipase activity by
astilbin from the leaves of Engelhardtia chrysolepis.
AB - Astilbin, a dihydroflavonol rhamnoside isolated from the leaves of Engelhardtia
chrysolepis, enhanced the vanadate-stimulated release of lipoprotein lipase (LPL)
activity from rat isolated fat pads. N-[2-(Methyl-amino)ethyl]-5
isoquinolinesulfonamide (H-8), a potent inhibitor of cAMP-dependent protein
kinase (PKA), markedly inhibited the enhancement by astilbin. Lipolysis in the
fat pads was stimulated by astilbin alone in a dose-dependent manner and this
stimulation was suppressed in the presence of vanadate, probably due to its
antilipolytic action. A significant enhancement by astilbin was observed with
increasing effects of vanadate on cAMP content in the fat pads and on cAMP
phosphodiesterase (PDE) activity in the particulate fraction although astilbin
alone showed only a slight increase in the cellular cAMP content and PDE
activity. Astilbin may enhance the vanadate-stimulated release of LPL activity
through a synergistic effect on an increase in the cellular cAMP content produced
by vanadate accompanied by more potent activation of PKA.
PMID- 9635511
TI - Protective effect of ceftriaxone against the nephrotoxicity of isepamicin
administered once daily in rats.
AB - The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was
investigated. For 14 d, Wistar rats were administered either ceftriaxone 100
mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone
isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a
significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as
compared with the control animals which received saline (p<0.01). However, the
increase in NAG level was markedly less when isepamicin was administered in
combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine
NAG activity. Serum creatinine levels were significantly higher in animals
treated with isepamicin alone than in control animals (p<0.01) or animals
receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of
treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the
renal intracortical accumulation of isepamicin (p<0.01). Histopathologically,
ceftriaxone induced very few cellular alterations and considerably reduced the
manifestation of typical signs of isepamicin nephrotoxicity. This investigation
demonstrates that ceftriaxone protects animals against isepamicin-induced
nephrotoxicity.
PMID- 9635512
TI - Effect of potassium sorbate on cellular GSH level and lipid peroxidation in
cultured rat hepatocytes.
AB - Change in cellular reduced glutathione (GSH) level was examined after the
addition of 1-10 mM potassium sorbate (SA-K) to cultured rat hepatocytes. The
cellular GSH content was decreased to the lowest level at 6 h after the addition
of SA-K, and then gradually returned to the normal level except for hepatocytes
exposed to 10 mM SA-K. Although the decrease in GSH level was not associated with
lactate dehydrogenase (LDH) leakage in hepatocytes exposed to SA-K up to the
concentration of 5 mM, cell injury was caused in cells exposed to 10 mM SA-K.
When eicosapentaenoic acid was added in conjunction with various concentrations
of SA-K to hepatocytes, peroxidation of the fatty acid was accelerated in
parallel with the decrease in cellular GSH level. The enhanced lipid peroxidation
in the hepatocytes co-exposed to SA-K and eicosapentaenoic acid (EPA) induced the
development of cell injury. These results suggest that hepatocytes exposed to SA
K become susceptible to oxidative stress such as lipid peroxidation.
PMID- 9635513
TI - Uptake of doxorubicin by cultured kidney epithelial cells LLC-PK1.
AB - The renal handling of doxorubicin (DXR) was investigated using a kidney
epithelial cell line, LLC-PK1. The uptake of DXR by LLC-PK1 cells cultured on
plastic dishes was shown to be temperature and concentration dependent. The
initial uptake of DXR was slightly saturable. The Km and Vmax of the saturable
component were calculated to be 20.2 microM, and 0.355 nmol/mg protein/10 min,
respectively. The release of DXR from LLC-PK1 cells was very slow at 37 degrees C
and almost negligible at 4 degrees C, indicating that most of the DXR in the
cells irreversibly binds to cellular constituents and that only a slight amount
of unbound DXR participates in the efflux out of the cells. DXR uptake at 37
degrees C was significantly decreased in the presence of 2,4-dinitrophenol.
However, organic cations and aminoglycoside antibiotics, such as
tetraethylammonium, N1-methylnicotinamide, guanidine, gentamicin and neomycin,
did not inhibit DXR uptake, suggesting that a process distinct from the organic
cation transport system and absorptive endocytosis might be involved in the
uptake of DXR by LLC-PK1 cells.
PMID- 9635514
TI - Isolation of a major metabolite (i-OHAP) of aprindine and its identification as N
[3-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol.
AB - i-OHAP, a major metabolite of aprindine (AP), was isolated by TLC from rat feces
and identified as N-13-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan-5-ol,
based on 1H-NMR, the H-H correlation spectroscopy (COSY) spectrum, MS and LC-MS.
Its structure was also confirmed by comparison with the synthesized compound. The
hydroxy group of i-OHAP was located at the 5-position of the indan ring. AP is a
prochiral compound, and the metabolism of AP to i-OHAP was stereoselective. The
ratio of (+)/(-)-i-OHAP in rat feces and in human urine was about 5 and 15,
respectively.
PMID- 9635515
TI - A rapid assay of granisetron in biological fluids from cancer patients.
AB - A convenient high-performance liquid chromatography (HPLC) was developed for the
rapid assay of granisetron (GRN) in biological fluids, such as serum, urine, and
pleural effusion, from cancer patients. Extrelut-1 was used for the solid-phase
extraction. HPLC was carried out using a LiChroCART cartridge column packed with
Lichrospher 100 CN and a mobile phase consisting of 0.1 M acetate buffer (pH 3.5)
and acetonitrile (7:3). A fluorescence detector of 290 nm for excitation and 365
nm for emission was used. The standard curve was linear over the range of 2 to
100 ng/ml of GRN. Assay precision, expressed as a coefficient of variation
(C.V.), was in the range of 0.9-5.4% in the within-day assay and 2.5-6.9% in the
between-day assay, respectively. GRN was well separated on the HPLC chromatogram
from drugs such as etoposide, metclopramide, ondansetron, and domperidone which
are often used together with GRN. It was suggested that the present method is
useful for the rapid monitoring of GRN in the serum, urine, and pleural effusion
of patients undergoing cancer chemotherapy.
PMID- 9635516
TI - Inhibitory effect of 2,5-dimethylpyrazine on oxytocic agent-induced uterine
hypercontraction of normal or pregnant female rats.
AB - Intraperitoneal administration of 2,5-dimethylpyrazine (2,5-DMP) was found to
inhibit oxytocin- and prostaglandin F2alpha-induced tetanic uterine contractions
in normal or pregnant female rats. This suggests that 2,5-DMP may be used as a
countercontraction agent or relaxant for preventing oxytocic agent-induced
medical accident including uterine rupture or pressure death of the fetus due to
uterine contractions.
PMID- 9635517
TI - Inhibition of S-warfarin metabolism by nonsteroidal antiinflammatory drugs in
human liver microsomes in vitro.
AB - We studied the inhibition of S-warfarin metabolism by nonsteroidal
antiinflammatory drugs (NSAIDs) in human liver microsomes in vitro. After
screening for potential inhibitors among ten NSAIDs using human recombinant
cytochrome P450, inhibition kinetic parameters were estimated using human liver
microsomes. Phenylbutazone and bucolome were suggested to increase the unbound
steady-state level of S-warfarin about four- and five-fold, respectively, as
estimated from these metabolic parameters.
PMID- 9635518
TI - Potent retinoid synergists with a diphenylamine skeleton.
AB - 4-[N-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)amino]benzoic acid (5)
exhibited weak retinoidal and retinoid synergistic activities in HL-60 cell
differentiation assay. N-Alkylation of 5 caused decrease or loss of
differentiation-inducing activity, but enhanced the synergistic activity with a
synthetic retinoid Am80 (2), as reflected in the potent synergistic EC50 (SEC50)
values of DA023 (11, 1.6 x 10(-10) M) and DA113 (14, 1.4 x 10(-10) M) in the
presence of 1.0 x 10(-10) M Am80 (2).
PMID- 9635519
TI - Novel thiazolidinedione derivatives with retinoid synergistic activity.
AB - Several arylmethylidene thiazolidinediones were synthesized and their retinoidal
activities were examined. TZ181 (7a), having a benzanilide skeleton, exhibited
differentiation-inducing activity in HL-60 cell assay, while TZ191 (7b), the N
methylated analog of TZ181 (7a), TZ245 (9) and TZ335 (10) acted as retinoid
synergists like the RXR-selective ligand, LGD1069 (5).
PMID- 9635520
TI - Controlled-release morphine tablets in patients with chronic cancer pain: a
narrative review of controlled clinical trials.
AB - BACKGROUND: Controlled-release (CR) morphine tablets have become routine therapy
in the management of cancer pain. Compared with immediate-release (IR) morphine,
this formulation provides the benefit of dosing every 12 hours. METHODS: This
study reviewed the 10 published, well controlled, repeated-dose, comparative
studies with CR morphine tablets administered every 12 hours to patients with
cancer pain. RESULTS: CR morphine tablets were uniformly effective; 98% of
patients completed a treatment course of every-12-hours therapy. Although the
effective analgesic dose varied considerably from study to study (range, 90-330
mg per day), pain was well controlled with CR morphine tablets as the primary
analgesic. Mean pain scores, converted to a common 10-point scale, ranged from
1.1-2.9 across all studies. There was only occasional need for IR morphine rescue
medication (range, 2-39 mg per day). The mean discontinuation rate because of
side effects or lack of every-12-hours efficacy was 2%. In seven studies that
used IR morphine as the comparative agent, CR morphine tablets were found to be
equally effective as IR morphine. CONCLUSIONS: Twice-daily dosing of CR morphine
provides convenient, safe, and effective relief of cancer pain.
PMID- 9635521
TI - Long-term survival of patients with stage IV gastric carcinoma.
AB - BACKGROUND: Survival of patients with Stage IV (based on general rules
established by the Japanese Research Society for Gastric Cancer) gastric
carcinoma often is unfavorable. Among patients with a poor prognosis, a few do
survive > 5 years. The authors examined pathologic and biologic features of
tumors of long term survivors. METHODS: The authors analyzed data from 442
patients with Stage IV gastric carcinoma, including 20 surviving for > 5 years
after gastrectomy (Group A) and 422 who died of gastric carcinoma within 5 years
(Group B). Mutant p53 was immunohistochemically stained using the monoclonal
antibody PAb1801. Proliferative activity was estimated by argyrophilic nuclear
organizer region (AgNOR) staining and proliferating cell nuclear antigen (PCNA)
staining. RESULTS: Group A had smaller and more localized tumors than Group B (P
< 0.05 and P < 0.01, respectively). Lymphatic or venous invasion and peritoneal
dissemination were less frequent in Group A than in Group B (P < 0.01).
Abnormalities of p53 expression were found in 3 of the 14 tumors in Group A
(21%), a value significantly lower than the 58 of 118 tumors in Group B (49%; P <
0.05). AgNOR count and percentage of PCNA labeling were not significantly
different between Groups A and B. A multivariate analysis showed that lymph node
dissection, liver metastasis, gastric resection, venous invasion, and tumor size
were independent prognostic factors. CONCLUSIONS: Even in patients with Stage IV
gastric carcinoma, radical gastrectomy and extensive lymph node dissection can
lead to long term survival. The authors believe that combination analysis of
pathologic features and p53 overexpression predict length of survival for
patients with Stage IV gastric carcinoma.
PMID- 9635522
TI - Race, treatment, and survival among colorectal carcinoma patients in an equal
access medical system.
AB - BACKGROUND: The aim of this study was to assess the influence of race on the
treatment and survival of patients with colorectal carcinoma. METHODS: This
retrospective cohort study included all white or black male veterans given a new
diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers
nationwide. After adjusting for patient demographics, comorbidity, distant
metastases, and tumor location, the authors determined the likelihood of surgical
resection, chemotherapy, radiation therapy, and death in each case. RESULTS: Of
the 3176 veterans identified, 569 (17.9%) were black. Bivariate analyses and
logistic regression revealed no significant differences in the proportions of
patients undergoing surgical resection (70% vs. 73%, odds ratio 0.92, 95%
confidence interval 0.74-1.15), chemotherapy (23% vs. 23%, odds ratio 0.99, 95%
confidence interval 0.78-1.24), or radiation therapy (17% vs. 16%, odds ratio
1.10, 95% confidence interval 0.85-1.43) for black versus white patients. Five
year relative survival rates were similar for black and white patients (42% vs.
39%, respectively; P=0.16), though the adjusted mortality risk ratio was modestly
increased (risk ratio 1.13, 95% confidence interval 1.01-1.28). CONCLUSIONS:
Overall, race was not associated with the use of surgery, chemotherapy, or
radiation therapy in the treatment of colorectal carcinoma among veterans seeking
health care at Veterans Affairs Medical Centers. Although mortality from all
causes was higher among black veterans with colorectal carcinoma, this finding
may be attributed to underlying racial differences associated with survival. This
study suggests that when there is equal access to care, there are no differences
with regard to race.
PMID- 9635523
TI - A phase II trial of 5-fluorouracil, leucovorin, and carboplatin in patients with
unresectable biliary tree carcinoma.
AB - BACKGROUND: Unresectable adenocarcinoma of the biliary tree are associated with a
very poor prognosis. 5-fluorouracil (5-FU) combination regimens have produced
objective response rates in approximately 10-20% of patients. Leucovorin
increases the selective cytotoxicity of 5-FU. There also are encouraging reports
of carboplatin in combination with 5-FU in other gastrointestinal tract
malignancies. METHODS: Fourteen consecutive eligible patients were treated with a
combination of carboplatin, 300 mg/m2, intravenously (i.v.) on Day 1 only and 5
FU, 400 mg/m2, i.v. with leucovorin, 25 mg/m2, i.v. on Days 1-4. All patients
were required to have a histologically confirmed diagnosis and measurable
disease. Patients were evaluated for response, survival, and toxicity. RESULTS: A
total of 48 cycles of therapy were delivered. The median survival was 5 months.
One patient achieved complete remission and two others partial remission, for a
total response rate of 21.4%. Four additional patients had stable disease for a
median duration of 4 months. The therapy was well tolerated, with moderate
myelosuppression as the main dose-limiting toxicity. CONCLUSIONS: The current
combination regimen of leucovorin-modulated 5-FU with carboplatin is well
tolerated with appropriate supportive care, produces significant objective
responses in 21% of patients with biliary tree carcinoma, and should be
considered for the treatment of this disease.
PMID- 9635524
TI - Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma.
AB - BACKGROUND: Animal experiments and epidemiologic data have suggested that the use
of nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the incidence of
large bowel carcinoma. Our purpose was to assess the relation of the use of
aspirin and nonaspirin NSAIDs with the risk of large bowel carcinoma. METHODS: A
population-based case-control study of colon and rectal carcinoma was conducted
in Massachusetts from 1992 to 1994. Data on NSAID use and risk factors for large
bowel carcinoma were collected by interview from 1201 incident cases of large
bowel carcinoma and 1201 controls matched by age, gender, and area of residence.
RESULTS: Regular NSAID use that continued into the year before diagnosis was
associated with a significantly decreased relative risk estimate overall (0.7;
95% confidence interval [CI], 0.5-0.8) and among Stage II-IV tumors (0.6; 95% CI,
0.4-0.7). There was no reduction in risk for discontinued use. The inverse
association with regular continuing use was present across age and gender and for
both colon and rectal carcinoma. Similar inverse associations were present for
regular continuing use of aspirin and nonaspirin NSAIDs. There was no significant
evidence of a trend for the relative risk to decrease as the duration of use
increased, nor was there a trend across the dose of aspirin, which ranged from
less than one-half of a 325 mg tablet per day to > or = 2 tablets per day.
Discontinuation of use in response to symptoms of carcinoma did not appear to
explain the inverse association, nor did bias related to diagnosis of the
carcinoma. CONCLUSIONS: These data add to the growing body of evidence that
suggests a protective effect of NSAIDs against large bowel carcinoma.
PMID- 9635525
TI - Epstein-Barr virus-associated nonsmall cell lung carcinoma: undifferentiated
"lymphoepithelioma-like" carcinoma as a distinct entity with better prognosis.
AB - BACKGROUND: Epstein-Barr virus (EBV) infection in nonsmall cell lung carcinoma
(NSCLC) has been demonstrated in some ethnic groups. The pathobiology and the
role of EBV and oncoprotein expression in these tumors have not been studied
extensively. In this study, the authors investigated EBV-encoded RNA-1 (EBER1)
transcripts by in situ hybridization and the expression of latent membrane
protein-1 (LMP-1) and bcl-2 protein by immunohistochemistry in NSCLC patients
from Taiwan, where nasopharyngeal carcinoma is endemic. METHODS: A total of 127
cases of NSCLC (43 cases of squamous cell carcinoma [SCC], 67 cases of
adenocarcinoma [AD], 12 cases of large cell carcinoma [LCC], and 5 cases of
lymphoepithelioma-like carcinoma [LE]) were included. A sensitive polymerase
chain reaction-derived, digoxigenin-labeled DNA probe for in situ detection of
EBER1 transcripts was performed for the detection of EBV. Immunohistochemistry
using the avidin-biotin-immunoperoxidase method was also performed to evaluate
the expression of bcl-2 and LMP-1. RESULTS: EBER1 was detected in 11 of the 127
NSCLC cases (8.7%; 6 SCC cases and 5 LE cases). All 5 LE cases were EBV-positive,
whereas only 6 of the 43 SCC cases (14%), 0 of 67 AD cases, and 12 LCC cases were
EBV-positive (P < 0.05). All five LE cases showed diffuse, strong, positive
staining of tumor cells; five of the six SCC cases showed diffuse but weak
staining. Among the nontumor epithelial cells, there was no EBER1 staining of any
of the 11 EBER1-positive cases. The mean age of the LE patients was 10 years
younger than that of the patients with other histological types. All 5 LE
patients were nonsmokers, whereas 3 of the 6 patients with EBER1-positive SCC
(50%) were smokers. EBER1 expression did not correlate with the 2-year survival
rate of overall cases, but all 5 LE patients were alive without clinical evidence
of disease at last follow-up. Gender, lymph node or distant metastasis, and
clinical stage were not found to have any correlation with EBER1 expression (P >
0.05). All LE cases had bcl-2 oncoprotein expression (100%). This frequency was
significantly different from other histologic types (P < 0.05). The LMP-1
detection rate was low and demonstrated no correlation with bcl-2 expression.
CONCLUSIONS: In this study, the authors found that the primary LE of the lung is
associated with young age, a history of not smoking, high bcl-2 immunoreactivity,
and better survival rate. These characteristics demonstrate that EBV-associated
LE of the lung is a unique entity. The findings of the current study suggest that
EBV infection may play a different role in the tumorigenesis of primary LE of the
lung than it does in other EBER1-positive NSCLCs.
PMID- 9635526
TI - Relation between cellular doxorubicin binding ability to nuclear DNA and
histologic response to preoperative chemotherapy in patients with osteosarcoma.
AB - BACKGROUND: Although chemosensitivity to antiosteosarcoma agents is the most
important prognostic factor in human osteosarcoma, none of the many
chemosensitivity tests reported previously are reliable and clinically useful. In
this study, the authors investigated the reliability and clinical availability of
doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as
a new chemosensitivity test for osteosarcoma. METHODS: Doxorubicin (adriamycin
[ADM]) binding ability (%AB) to nuclear DNA in isolated osteosarcoma cells was
assessed by ABA in 14 patients with primary osteosarcoma who were treated with
preoperative chemotherapy containing ADM and 6 patients with relapsed
osteosarcoma after intensive chemotherapy. Histologic responses to preoperative
chemotherapy were evaluated by percentage of tumor necrosis (%necrosis). RESULTS:
Four of the 14 patients with primary osteosarcoma had %AB > 80% (97.3+/-3.7%) and
demonstrated good histologic responses (>90% of %necrosis) to preoperative
chemotherapy, whereas the remaining 10 patients had %AB < 80% (38.9+/-21.0%) and
demonstrated poor responses. Patients with recurrent osteosarcoma that was
clinically evaluated to be resistant to previous chemotherapy also had low %AB
(34.2+/-28.3%). CONCLUSIONS: Because the results of the current study revealed
that ABA is useful for predicting chemosensitivity to chemotherapy with ADM as
well as chemotherapy without ADM for patients with osteosarcoma, and because ABA
technically is simple and results can be assessed rapidly, the authors conclude
that ABA is a clinically useful chemosensitivity test for patients with
osteosarcoma.
PMID- 9635527
TI - Mesenchymal chondrosarcoma of the jaw bones: clinicopathologic study of 19 cases.
AB - BACKGROUND: Patients with mesenchymal chondrosarcomas in general have a 5-year
survival rate ranging from 42-54.6% and a 10-year survival rate of 28%. Nineteen
cases of mesenchymal chondrosarcoma of the jaw bones were reviewed to study their
clinicopathologic features and to compare their clinical behavior with that of
mesenchymal chondrosarcomas of other locations. METHODS: The patients were 10
males and 9 females (age range, 2-51 years). Sixteen patients were age < 30
years, and the average age at presentation was 19 years. Eleven tumors involved
the mandible and eight involved the maxilla. RESULTS: Histologically, the classic
picture of a bimorphic tumor, composed of islands of well differentiated hyaline
cartilage juxtaposed to a small cell undifferentiated malignancy, was present in
every case. Resection, including hemimandibulectomy and hemimaxillectomy, was the
main treatment in 16 patients. Seven patients had local recurrence, and five
patients developed distant metastases. Six patients died of disease, and the 5
year and 10-year survival rates were 82% and 56%, respectively. CONCLUSIONS:
Mesenchymal chondrosarcoma of the jaw bones appears to have a more indolent
course than mesenchymal chondrosarcoma of other anatomic
PMID- 9635528
TI - Pathologic femoral fracture after periosteal excision and radiation for the
treatment of soft tissue sarcoma.
AB - BACKGROUND: Surgical resection and adjuvant radiation therapy are standard
therapy for soft tissue sarcomas. When the tumor approximates bone, periosteal
excision may be necessary. It was hypothesized that periosteal stripping and
radiation therapy would increase the rate of pathologic fracture. METHODS: The
soft tissue sarcoma data base at the Memorial Sloan-Kettering Cancer Center was
used to identify a consecutive series of 205 patients who were treated over a 15
year period (1982-1997). All patients had a soft tissue sarcoma of the thigh,
which was managed by limb-sparing surgery and radiation therapy. Patients who had
bone invasion by tumor or bone resection were not included. RESULTS: Nine
patients, including eight women and one man, developed a femoral fracture in an
area of previous radiation and surgery. All nine patients had undergone
periosteal excision. The risk of fracture, by Kaplan-Meier survivorship, was 29%
at 5 years if the resection included periosteum (P < 0.0001). Cox multiple
regression analysis showed that periosteal excision was the only independent
prognostic factor for the entire set of 205 patients at risk. However, for the
subset of 54 patients who had periosteal stripping, two factors were also found
to be prognostically important: female gender (P=0.022) and chemotherapy
(P=0.020). The risk of fracture was 47% and 45%, respectively. The treatment of
the fractures was difficult. There were four nonunions and three delayed unions.
CONCLUSIONS: Periosteal stripping and radiation therapy places the femur at high
risk of pathologic fractures, especially for female patients and patients
undergoing chemotherapy. When practical, the combination of periosteal stripping
and radiation should be avoided.
PMID- 9635529
TI - Inflammatory breast carcinoma incidence and survival: the surveillance,
epidemiology, and end results program of the National Cancer Institute, 1975
1992.
AB - BACKGROUND: Little is known about the cause of inflammatory breast carcinoma
(IBC), the most aggressive form of breast cancer. To the authors' knowledge, no
studies have investigated whether IBC risk factors are different from those for
breast carcinoma overall, and there has been only one report of IBC incidence and
survival patterns. METHODS: The authors used data from the Surveillance,
Epidemiology, and End Results program of the National Cancer Institute for the
period 1975-1992 to calculate age-adjusted incidence and survival rates for 913
white and 121 African American women with IBC involving dermal invasion of
lymphatic ducts and 166,375 white and 13,674 African American women with other
types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992,
IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000
person-years and among African Americans from 0.6 to 1.1 cases. However, rates
for African Americans varied due to the small numbers of IBC cases. The twofold
increase in IBC incidence was higher than that observed for non-IBC during the
same period (27% for African Americans and 25% for whites). IBC patients were
significantly younger at diagnosis than non-IBC patients; and among both IBC and
non-IBC patients, African Americans were younger than whites. Overall survival
was significantly worse for IBC patients than for non-IBC patients and for
African Americans than for whites. Among whites, 3-year survival improved more
for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992,
increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for
non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence
trends and age at diagnosis, particularly according to race, highlight the need
for further investigation of the differences between IBC and non-IBC incidence.
PMID- 9635530
TI - The extent of proliferative and apoptotic activity in intraductal and invasive
ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl
transferase-mediated digoxigenin-11-dUTP nick end labeling.
AB - BACKGROUND: The balance among cell proliferation, cell differentiation, and cell
death determines the cell number in a population as well as the size or even the
stage of a tumor. Thus, to improve our understanding of the pathogenesis of
neoplasms, it is important to investigate the regulation of both cell
proliferation and cell death. METHODS: This study examined the occurrence of
apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal
carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal
carcinomas (IDC). Terminal deoxynucleotidyl transferase-mediated digoxigenin-11
dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were
used in the examination. A ladder of DNA fragments induced by apoptosis was
demonstrated by means of DNA agarose gel electrophoresis in 10 of the available
TUNEL positive and negative samples. RESULTS: The results were correlated with
p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein
expression, which would suggest association with apoptosis by
immunohistochemistry. The apoptosis and proliferation of each cancer were
expressed as the number of tumor cells undergoing apoptosis and proliferation per
1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS
than in IDC (21.9+/-6.8 vs. 4.0+/-0.9, P < 0.001), and the proliferation activity
was significantly higher in IDC than in DCIS (16.8+/-6.5 vs. 3.5+/-0.8, P <
0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was
significantly higher in IDC than in DCIS (3.26 vs. 0.42, P=0.001). In DCIS,
apoptosis was correlated with p53 (r=0.663, P=0.005), and p53 had a reverse
correlation with bcl-2 (r=0.620, P= 0.018). Moreover, bcl-2 expression was
associated with ER (P=0.028) and PR (P= 0.005) expression in both DCIS and IDC.
CONCLUSIONS: The results of this study show that a higher degree of apoptosis and
lower proliferation activity in intraductal carcinoma result in a steady-state,
self-renewing condition in which net growth of the tumor is rare. The results
also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and
PR.
PMID- 9635531
TI - Mammary ductal carcinoma in situ with microinvasion.
AB - BACKGROUND: The natural history of patients with intraductal carcinoma (DCIS) and
microinvasion is poorly defined, and the clinical management of these patients,
with particular reference to management of the axilla, has been controversial.
Previous studies of this lesion have used varied and/or arbitrary criteria for
the evaluation of microinvasion. METHODS: Thirty-eight DCIS lesions with
microinvasion (n=29) or probable microinvasion (n=9), diagnosed during the period
1980-1996, were retrospectively analyzed after cases not treated with mastectomy
and axillary lymph node dissection were excluded. Microinvasion was defined as a
single focus of invasive carcinoma < or = 2 mm or up to 3 foci of invasion, each
< or =1 mm in greatest dimension. RESULTS: The patients were all females with a
mean age of 56.4 years. DCIS was of comedo (n=31) or papillary (n=7) subtype.
Microinvasion was often associated with an altered, desmoplastic stroma (55%) or
a lymphocytic infiltrate (39%). The foci of microinvasion ranged from 0.25 to
1.75 mm (mean, 0.6 mm), with an aggregate mean size of 1.1 mm (range, 0.25-2.25
mm). Foci of microinvasion, ranging from 1 to 3 (mean, 1.7), were adjacent to
DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of
foci of microinvasion. Axillary lymph node dissections yielded a mean of 19.3
lymph nodes (range, 7-38), and all lymph nodes were negative for metastasis. None
of 33 patients, followed for a mean of 7.5 years (range, 1.0-14.4 years),
developed local recurrence or metastasis. CONCLUSIONS: The cases of microinvasive
carcinoma examined in this study, as defined above, were not associated with
axillary lymph node metastases and appeared to be associated with an excellent
prognosis. Further study is indicated to determine the appropriate management and
long term prognosis of patients with this lesion.
PMID- 9635532
TI - How reminders given to patients and physicians affected pap smear use in a health
maintenance organization: results of a randomized controlled trial.
AB - BACKGROUND: Despite its effectiveness as a method of controlling cervical
carcinoma, the use of Pap smear testing remains incomplete, and its promotion in
the primary care setting provides an important opportunity for intervention.
METHODS: The authors conducted a randomized controlled trial that involved three
sites of a health maintenance organization (HMO) serving an urban minority
population. Their aim was to evaluate the impact of reminders given to patients
and physicians on site visitation by patients and Pap smear use. Eligible women
(n=5801) were randomly assigned to 1 of 4 intervention combinations (in which
reminders were given to either the patient or the physician, to both, or to
neither). If they were ineligible for patient reminder intervention, patients
were randomized only to physician reminder intervention (the presence or absence
of it). The letter of reminder mailed to the patient invited women due for Pap
smears to visit the HMO site, and the reminder for physicians was a medical
record notice that a Pap smear was due. Logistic and survival analyses were used
to investigate the correlation of intervention status with visitation, interval
of time to a visit, and Pap smear use. RESULTS: In the primary intent-to-treat
analysis, there was no significant effect of either patient or physician reminder
interventions on rates of visitation or Pap smear completion. The secondary
efficacy analyses demonstrated no overall effect of either patient or physician
reminders, but effects among subgroups of women at individual HMO sites were
noted. At Site 3, there was an apparent increase in time to the next visit among
the subgroup of women with a chronic illness (16 weeks with intervention vs. 9
weeks without). With the physician reminder, the odds that a Pap smear would be
given during the study year were increased among women without a previous Pap
smear at Site 1 (adjusted odds ratio=1.39) and those with a chronic illness at
Site 2 (adjusted odds ratio=3.38). CONCLUSIONS: Reminders given to patients and
physicians had a limited impact on visitation by patients to the HMO sites or Pap
smear completion. Although some subgroups of women may benefit, the authors also
observed a possibly unfavorable impact among other subgroups. These results
emphasize the importance of identifying more effective interventions, targeting
them to women most likely to benefit, and not overlooking the possibility that
preventive intervention will have an unanticipated adverse effect.
PMID- 9635533
TI - Squamous intraepithelial lesions of the cervix, invasive cervical carcinoma, and
immunosuppression induced by human immunodeficiency virus in Africa. Dyscer-CI
Group.
AB - BACKGROUND: Squamous intraepithelial lesions (SILs) of the cervix are associated
with human immunodeficiency virus (HIV) infection, but multiple risk factors must
be considered in this context. The authors performed a cross-sectional study to
assess the prevalence of and the factors associated with SILs and invasive
cervical carcinoma (ICC). METHODS: In Abidjan, Cote d'Ivoire, women were
recruited from three outpatient gynecology clinics and screened for both cervical
disease and HIV infection. A CD4 cell count was performed for HIV-infected women.
RESULTS: A total of 2198 women were included in the study. The prevalence of HIV
infection was 21.7%. Of the 2170 women who underwent a cervical screening, 254
(11.7%) presented with a dysplasia or neoplasia: 7.6% had low grade SILs (LSILs),
3.3% had high grade SILs (HSILs), and 0.8% had ICCs. In multivariate analyses,
factors associated with these lesions were as follows: for LSILs, HIV-1
seropositivity, age <24 years, parity >1, consultation for genital infection, and
no use of oral contraception in the past; for HSILs, HIV-1 seropositivity,
chewing tobacco use, low educational level, and parity >1; and for ICCs, age >33
years, parity >3, and illiteracy. In women infected with HIV-1, the prevalence of
LSILs increased with a decrease in CD4 cell count, whereas this relation was not
found among patients with HSILs. ICCs were linked to HIV-2 infection, but not to
HIV-1 infection, in univariate analysis. CONCLUSIONS: In Africa, the prevalence
of SILs is high. The factors associated with precancerous and cancerous lesions
are different. Cancers in women infected with HIV-1 often may not reach the
invasive stage. These findings could have implications for cervical screening
programs in the future.
PMID- 9635534
TI - Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix: a possible
immunohistochemical marker of a favorable prognosis.
AB - BACKGROUND: The purpose of this study was to assess the prognostic significance
of the expression of estrogen receptor and cell cycle regulatory gene products in
cervical adenocarcinoma. METHODS: In 40 cases of adenocarcinoma of the uterine
cervix and 10 normal cervices, expression of estrogen receptor and cell cycle
regulatory gene products (cyclin E, p16, p21WAF1/CIP1, p27, p53, and Ki-67) was
studied using immunohistochemical techniques. The survival of the patients was
analyzed in terms of such variables as the expression of these molecules in the
tumor and conventional clinicopathologic features, and the Cox proportional
hazards model was used to predict the survival of patients with cervical
adenocarcinoma. RESULTS: Expression of estrogen receptor was consistently
observed in normal cervical glands, but in cervical adenocarcinoma it was lost
(in 28 cases) or significantly diminished (in 12 cases). Normal cervical
glandular cells were usually negative for the cell cycle regulatory gene
products, whereas 47.5-85% of cervical adenocarcinomas were positive for these
molecules. When the expression of these molecules was analyzed, significant
positive correlations were found between p16 and p27, cyclin E and p27, and
cyclin E and p21WAF1/CIP1. Univariate survival analysis revealed that the
presence of parametrial invasion, the presence of lymph node metastasis, negative
staining for p21WAF1/CIP1, and a moderately or poorly differentiated tumor all
correlated significantly with a poor prognosis. In a stepwise regression
analysis, the expression of p21WAF1/CIP1 and negative pelvic lymph nodes were the
best predictors of a favorable prognosis. CONCLUSIONS: Expression of p21WAF1/CIP1
correlated with a favorable prognosis for patients with cervical adenocarcinoma
and may serve as a useful marker of survival in cases of this disease.
PMID- 9635535
TI - Interstitial fluid pressure in cervical carcinoma: within tumor heterogeneity,
and relation to oxygen tension.
AB - BACKGROUND: Interstitial fluid pressure (IFP) is elevated in many animal and
human tumors. The authors assessed tumor IFP and its relation to tumor
oxygenation in a prospective clinical study of patients with cervical carcinoma.
METHODS: Measurements were made in 77 patients with cervical carcinoma prior to
treatment. IFP was measured in normal paravaginal submucosal tissue and at one to
five positions in the visible tumor with the patients anesthetized and in the
lithotomy position. Tumor oxygen tension was measured immediately prior to IFP
using a polarographic needle electrode. Patients were treated with radiotherapy
only. Response was evaluated 3 months after the completion of radiotherapy.
RESULTS: There was substantial variation in IFP from region to region in some
tumors. The mean IFP in individual tumors ranged from 3 to 48 millimeters of
mercury (mmHg). The overall mean and median values for the entire patient group
were 19 mmHg and 17 mmHg, respectively. IFP was significantly higher in tumor
tissue than in normal tissue (P < 0.0001). Tumors with high IFP were more likely
to be hypoxic (P < 0.007) and less likely to regress completely with radiotherapy
(P < 0.04). CONCLUSIONS: IFP in cervical carcinoma is elevated above normal
tissue values. Multiple measurements are needed to evaluate IFP in these tumors.
High IFP is associated with hypoxia and may provide information about the
mechanism of hypoxia on which treatment can be based.
PMID- 9635536
TI - Cystic embryonal sarcoma of kidney: a case report.
AB - BACKGROUND: Morphologic analysis of malignant renal tumors of childhood and
adolescence has resulted in the identification of a variety of tumor types with
characteristic histology and clinical behavior. The authors report a case of
renal sarcoma in a 19-year-old male that differs in morphology from the various
established categories of primitive renal tumors. METHODS: Sections taken from
the nephrectomy specimen were stained by routine methods and by
immunohistochemistry for stromal and epithelial markers, and for proliferation
markers. In addition, ultrastructural studies were undertaken. RESULTS: The
tumor, which the authors termed cystic embryonal sarcoma, was comprised of poorly
differentiated malignant mesenchyme in a myxoid stroma. Numerous epithelial-lined
cysts were present. The distribution of the cysts and proliferation kinetics of
cyst-lining epithelial cells suggested that they were derived from entrapped
renal tubules. The tumor showed early recurrence postoperatively and after
aggressive chemotherapy. The pathologic features and clinical behavior of the
tumor resemble those of 2 previously reported cases and an additional 25 cases
from the files of the National Wilms' Tumor Study Pathology Center. CONCLUSIONS:
The clinical and histologic features of cystic embryonal sarcoma differ from
those of other renal tumors of childhood and adolescence, and the tumor appears
to be a novel form of renal malignancy.
PMID- 9635537
TI - Plasma glutathione S-transferase P1-1 levels in patients with head and neck
squamous cell carcinoma.
AB - BACKGROUND: Many tumors contain high amounts of the detoxification enzyme
glutathione S-transferase P1-1 (GSTP1-1). Elevated levels of GSTP1-1 have also
been detected in serum and plasma from patients with gastrointestinal, lung, or
head and neck tumors. The authors of this report evaluated the role of GSTP1-1 as
a plasma tumor marker in patients with head and neck squamous cell carcinoma
(HNSCC) of the larynx, hypopharynx, or oropharnyx and in patients with benign
head and neck lesions (BHNL). METHODS: GSTP1-1 levels were measured in EDTA
plasma combined with ethylenediaminetetraacetic acid using a recently developed
sensitive and specific sandwich enzyme-linked immunoadsorbent assay. A normal
reference level with an upper limit of 21.8 microg GSTP1-1 per liter of plasma
was calculated from results obtained with samples from 230 blood donors. RESULTS:
Median GSTP1-1 levels in samples from 53 patients with oral/oropharyngeal SCC
(10.6 microg/L; range, 3.7-46.1 microg/L), 12 patients with hypopharyngeal SCC
(11.9 microg/L; range, 5.2-146.6 microg/L), and 28 patients with laryngeal SCC
(14.4 microg/L; range, 6.4-141.5 microg/L) were significantly elevated when
compared with plasma GSTP1-1 levels in samples from 45 patients with BHNL (8.1
microg/L; range, 3.3-32.3 microg/L; P < 0.0001, P < 0.01, and P < 0.0001,
respectively). However, only 6 of 53 patients (11%) with oral/oropharyngeal SCC,
1 of 12 patients (8%) with hypopharyngeal SCC, and 6 of 28 patients (21%) with
laryngeal SCC had plasma GSTP1-1 levels above the upper limit of the normal
reference level. Thus, only 13 of 93 patients (14%) with HNSCC had elevated
plasma GSTP1-1 levels overall. No significant relation between plasma GSTP1-1
levels and TNM classification of the tumors was observed. CONCLUSIONS: GSTP1-1 is
not a suitable plasma tumor marker for HNSCC.
PMID- 9635538
TI - Application of the international prognostic index in a study of Chinese patients
with non-Hodgkin's lymphoma and a high incidence of primary extranodal lymphoma.
AB - BACKGROUND: Chemotherapy containing anthracycline is the standard initial
treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International
Prognostic Index (IPI) is widely accepted as the standard tool for determining
the prognosis of patients with this disease. However, the data on which the IPI
was based primarily came from studies conducted in Western countries. It may not
be directly applicable to Asian populations, in which the incidence of primary
extranodal lymphoma (PENL) is known to be high. METHODS: The authors conducted a
retrospective study of 218 patients with aggressive NHL who were treated with
chemotherapy. They analyzed the distribution of stage and pathology, prognostic
factors, toxicity, and treatment outcome. The IPI was then applied and its
ability to identify distinct prognostic groups tested. RESULTS: Eighty-six
patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary
extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation,
bulk of disease, and histologic confirmation at an extranodal site). The most
common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar
ring (18.9%). The complete response rate of PENL patients to chemotherapy
containing anthracycline was 52%, as compared with 64% of the LNL group. The 5
year survival rates for patients with LNL and PENL were 57.4% and 52.1%,
respectively. The toxicity in the two patient groups was similar. Four of the
prognostic factors in the IPI-age, serum LDH, performance status, and disease
stage-predicted significantly different survival for PENL and LNL patients.
However, the number of extranodal sites involved was not a significant predictive
variable in PENL. CONCLUSIONS: The IPI was applicable to this Chinese population
in which the incidence of PENL was high, although the number of extranodal sites
did not achieve statistical significance as a risk factor. A proposal for
modification was made. Chemotherapy containing anthracycline was an effective
treatment for both PENL and LNL patients.
PMID- 9635539
TI - How should imipenem-cilastatin be used in the treatment of fever and infection in
neutropenic cancer patients?
AB - BACKGROUND: Imipenem-cilastatin (referred to hereafter as imipenem) is
administered at different doses as monotherapy or with other agents. Limited
comparisons of the alternatives exist. The authors compared the efficacy and
safety of several imipenem-containing regimens (ICRs) to determine the
appropriate dose and the need for combination therapy. METHODS: Between 1985 and
1994, febrile neutropenic patients were given ICRs according to the same
methodology on prospective trials at a referral cancer center. The ICRs were high
dose imipenem (HIP), high dose imipenem and amikacin (HIPA), high dose imipenem
and vancomycin (HIPV), and low dose imipenem and vancomycin (LIPV). RESULTS: The
overall response rates were comparable (70-77%). There was a univariate trend
toward better response among patients with pneumonia and documented infections
with unidentified organisms who received HIPV versus LIPV (P=0.06), as well as a
significantly better response among patients with gram positive infections who
received HIPV versus HIP (P=0.02) and HIPA (P=0.002). HIPV was a more effective
treatment for documented infections with identified organisms (P=0.05) and
bloodstream infections (P=0.04) than HIP; there was a univariate trend toward
better response among patients infected with gram negative organisms who received
HIPA versus HIP (P=0.12). Multivariate adjustment for baseline and prognostic
factors did not reveal a relative advantage for any regimen. No differences in
overall toxicities were observed between HIPV and LIPV. CONCLUSIONS: Imipenem
monotherapy is adequate treatment for most febrile neutropenic cancer patients.
Low dose imipenem could be effective and safe in uncomplicated cases without
pneumonia. Further studies are needed to establish the usefulness of low dose
imipenem in this context.
PMID- 9635540
TI - MIB-1 labeling index in nonpilocytic astrocytoma of childhood: a study of 101
cases.
AB - BACKGROUND: The prognosis of pediatric patients with nonpilocytic astrocytoma,
and in particular those with anaplastic astrocytoma, is somewhat unpredictable.
This study used MIB-1 monoclonal antibody, a proliferative marker that can be
used in formalin fixed paraffin embedded tissues, to study nonpilocytic pediatric
astrocytoma. METHODS: Astrocytoma, anaplastic astrocytoma, and glioblastoma
specimens excised from a total of 101 pediatric patients during the period from
January 1975 to September 1996 were retrieved from the authors' surgical
pathology file. Histologic grading of the specimens was performed based on a
modified Ringertz system. The proliferative potential of the tumors was estimated
by using the MIB-1 labeling index (LI), which was evaluated with morphologic
grades of tumors and survival of the patients. RESULTS: Of the 101 patients, 34
had astrocytoma, 33 had anaplastic astrocytoma, and 34 had glioblastoma. Their
mean survival times were 165.2+/-14.9 months (mean+/-standard error; SE), 46.1+/
9.9 months, and 21.8+/-5.6 months, respectively. The mean MIB-1 LI of different
tumor grades were as follows: astrocytoma, 3.9+/-4.3 (mean+/-standard deviation;
range, 0.0-21.6); anaplastic astrocytoma, 24.3+/-15.6 (range, 1.7-62.8); and
glioblastoma, 35.9+/-16.4 (range, 7.36-63.3). The mean survival of the entire
group of patients with LIs < or = 11 was 173.2+/-12.2 months (mean+/-SE), and the
mean survival of those with LIs > 11 was 20.3+/-4.1 months. The survival of
anaplastic astrocytoma patients with LIs < or = 11 was similar to that of
astrocytoma patients, whereas the survival of anaplastic astrocytoma patients
with LI > 11 was similar to that of patients with glioblastoma. CONCLUSIONS: The
results of the current study show that histopathologic grading can predict the
outcome for patients with astrocytomas and glioblastomas, whereas MIB-1 LI can
separate better and worse prognostic groups in patients with anaplastic
astrocytoma.
PMID- 9635541
TI - Informed consent in the Childrens Cancer Group: results of preliminary research.
AB - BACKGROUND: Informed consent is critical to the ethical conduct of pediatric
cancer clinical research. Research regarding such consent has been limited.
METHODS: After conducting a background survey of institutional practice from
principal investigators (PIs) at 113 Childrens Cancer Group (CCG) centers, the
authors obtained more detailed data regarding informed consent from 23 parents of
children recently enrolled in CCG research trials and from 23 clinician
investigators at 5 CCG institutions. RESULTS: Approximately 73% of PIs responded
to the background survey, providing context in which to interpret the more
detailed information. Parents reported that they found the informed consent
process helpful, although somewhat confusing. Satisfaction with informed consent
was not related to ethnicity or education level. Parents found discussion with
staff more helpful than the consent document, and the majority reported that the
amount of information conveyed was appropriate. Although only 3 parents (13%)
reported that too much information was given, nearly 50% of the investigators
believed too much information usually is provided. All investigators believed
that patients benefit from participation in CCG studies; the majority recommend
that the child be enrolled on study, and the majority believe the major obstacle
to good informed consent is parents' "state of shock." CONCLUSIONS: Parents
expressed general satisfaction with the consent process. By contrast, clinician
responses indicate dissatisfaction with the informed consent process. Future
research must include more centers and larger numbers of parents of children who
we enrolled as well as those who declined to participate in CCG studies, examine
consent in minority subgroups, and further investigate the role of clinician
investigators and their interaction with parents and children during the informed
consent process.
PMID- 9635542
TI - Introduction: augmentation of antidepressant medication.
PMID- 9635543
TI - Treating antidepressant nonresponders with augmentation strategies: an overview.
AB - This paper provides an overview of antidepressant nonresponse and the role of
augmentation strategies in the management of treatment-resistant depression. When
effective, the more widely used augmentation strategies, including lithium salts,
thyroid hormones, pindolol, buspirone, and psychostimulants, share two important
advantages when compared with "switching" strategies: avoidance of ill effects
associated with discontinuing the initial antidepressant and rapidity of onset of
action. Ideally, advances in the understanding of the neurobiology of mood
disorders and mechanisms of antidepressant response will permit a more efficient
and specific matching between patient, initial antidepressant, and subsequent
strategy for enhancing response to treatment.
PMID- 9635544
TI - The use of pindolol to potentiate antidepressant medication.
AB - Serotonin (5-HT) selective reuptake inhibitors (SSRIs) and monoamine oxidase
inhibitors are thought to have a delayed onset of antidepressant action
attributable in part to the decrease in firing activity of 5-HT neurons they
produce upon treatment initiation. As cell body 5-HT1A autoreceptors desensitize,
5-HT neuronal firing is restored. The agent pindolol, through its 5-HT1A receptor
blocking property, has been shown to prevent the initial decrease in firing of
rat 5-HT neurons associated with SSRI treatment. Four open-label studies put into
evidence a significant acceleration of the antidepressant effect of SSRIs when
combined with pindolol. Four of five placebo-controlled studies have confirmed
this observation. Controlled trials indicate that a greater rate of response may
be obtained by combining pindolol from the beginning of the SSRI treatment. The
strategy of adding pindolol to the regimen of SSRI-resistant patients also
appears to produce a therapeutic effect in a significant proportion of patients.
PMID- 9635545
TI - The use of thyroid supplements to augment antidepressant medication.
AB - Despite methodological flaws that limit conclusions, a considerable database
documents the efficacy of triiodothyronine (T3) as an augmentation strategy for
response to various classes of antidepressants. One study suggests that T3 and
lithium are of comparable efficacy in antidepressant nonresponders. No clear
biochemical or clinical predictors of preferential response to T3 have been
found. The role of T3 augmentation requires further evaluation, especially with
regard to dose and duration.
PMID- 9635546
TI - The use of lithium to augment antidepressant medication.
AB - Lithium is one of the most studied agents used to augment the pharmacologic
effect of antidepressant drugs, particularly in refractory depression. We
reviewed 22 case reports, 22 open trials, 5 open comparison studies, and 9
placebo-controlled studies of lithium augmentation and 6 studies in which
antidepressants were added to, or coadministrated with, lithium. The efficacy of
the augmentation therapeutic strategy is supported by these analyses, involving
969 patients. The optimal dose and the most effective blood levels of lithium are
unclear, but a reasonable strategy would be to start with low doses (600-900
mg/day) and, if necessary, to increase the doses to obtain a level in accordance
with the usual therapeutic range of blood levels (0.8-1.2 mEq/L). Some patients
respond quickly, but others need a long and combined treatment; it is thus
advantageous to prescribe lithium for at least 3 to 6 weeks. Despite the fact
that the mechanism of action of lithium augmentation is still unknown, all
refractory depressed patients can potentially be treated by lithium augmentation,
particularly bipolar patients, to obtain full prophylactic effect as soon as
possible.
PMID- 9635547
TI - Anxiolytic antidepressant augmentation.
AB - The administration of anxiolytic drugs often accompanies treatment with
antidepressant medications. Although benzodiazepines help alleviate the secondary
depressive symptoms of anxiety and sleep disturbance, they do not actually
enhance antidepressant response. On the other hand, the anxiolytic agent
buspirone does facilitate direct antidepressant response, largely through its
ability to activate both presynaptic and postsynaptic 5-HT1A receptors and thus
modulate serotonin release. Several case studies and open-label trials have
demonstrated the effectiveness of buspirone as an augmentation agent. Because
buspirone is also associated with few adverse effects, it appears to be both
effective and safe in the augmentation of antidepressant pharmacotherapy.
PMID- 9635548
TI - The use of anticonvulsants to augment antidepressant medication.
AB - Combination therapy that couples classical antidepressants with other
psychoactive compounds is one of the major therapeutic strategies in therapy
resistant depression. The authors review reports on the antidepressive effects of
the mood stabilizers carbamazepine and valproate and focus on the pharmacodynamic
and clinical aspects of combining these compounds with antidepressant drugs. In
addition, a pivotal study (N=10 outpatients) demonstrates the use and efficacy of
a low-dose combination therapy of carbamazepine and amitriptyline. It is
concluded that low-dose combination of classical antidepressants and mood
stabilizers appears to be well tolerated and highly effective.
PMID- 9635549
TI - Dopaminergic agents and stimulants as antidepressant augmentation strategies.
AB - Dopaminergic agents and stimulants have been used to manage depression when
conventional antidepressant treatments fail. We reviewed evidence for the role of
dopaminergic dysfunction in depression, the use of dopaminergic agents as
antidepressants, and the use of dopaminergic agents and stimulants as
antidepressant adjuncts. Dopamine may be part of the pathophysiology of
depression for a subset of patients. When used with caution and an appreciation
of the potential risk of abuse, dopaminergic agents and stimulants may be useful
for patients refractory to antidepressants alone.
PMID- 9635550
TI - Augmentation strategies with serotonergic-noradrenergic combinations.
AB - Combinations of antidepressants with both serotonergic and noradrenergic activity
may be especially effective and thus useful in treating refractory patients and
severely depressed patients. In the current report, studies of combinations of
serotonin selective reuptake inhibitors (SSRIs) and noradrenergic tricyclics or
of SSRIs and bupropion are reviewed, and practical issues pertaining to their use
are discussed.
PMID- 9635551
TI - Antidepressant augmentation: conclusions and recommendations.
PMID- 9635552
TI - A few comments on RSD (reflex sympathetic dystrophy)
PMID- 9635553
TI - Kinematic analysis of patients with spinal muscular atrophy during spontaneous
breathing and mechanical ventilation.
AB - Patients with infantile spinal muscular atrophy develop pectus excavatum along
with a severe restrictive syndrome as a result of failure to expand the upper
chest wall and lungs because of intercostal muscle weakness. By using an
automatic motion analyzer to provide three-dimensional computer analyses of
images sampled at 25 Hz, 9 spinal muscular atrophy Type II patients and 13
controls underwent kinematic analysis of thoracoabdominal movements partitioned
into the upper thorax, lower thorax, and abdominal volume compartments. The
analyses were performed during spontaneous breathing for the controls and during
spontaneous breathing and while using mechanically assisted ventilation for the
patients. Vital capacity, maximum inspiratory pressures, and nocturnal
oxyhemoglobin saturation and transcutaneous carbon dioxide tensions were also
measured for the patients. The kinematic data demonstrated a paradoxical
ventilatory pattern for the spontaneously breathing SMA patients with the
following inspiratory volume changes: upper thorax, -6.4+/-9.6%; lower thorax,
7.3+/-15.8%; abdominal, 99.1+/-21.3%. During mechanical ventilation, the
compartmental volume changes were as follows: upper thorax, 13.5+/-6%; lower
thorax, 13.7+/-7.9%; abdominal, 72.7+/-9.3%. This kinematic pattern is comparable
with that seen in spontaneously breathing normal subjects. We conclude that
mechanical ventilation can normalize kinematic volume changes during alveolar
ventilation and that this might help deter loss of thoracic compliance caused by
the chronic hypoventilation of the upper thoracic compartments. Kinematic
analysis may be helpful for choosing the ventilation parameters to optimize
therapeutic benefits.
PMID- 9635554
TI - Outcome, efficiency, and time-trend pattern analyses for stroke rehabilitation.
AB - We present a series of pattern analysis techniques using inpatient medical
rehabilitation as an example setting, stroke as a model diagnosis, and various
versions of the Functional Independence Measure-Function Related Groups as a case
mix adjuster. The pattern analytic approach uses severity-adjusted benchmarks to
distinguish among groups of patients whose outcomes and resource use patterns are
lower, typical, or higher than established ranges at set points in treatment.
Changing outcome and resource use patterns were illustrated for 1990, 1992, and
1995 discharges (n=34,734). These pattern analytic approaches are applicable to
any postacute care rehabilitation setting, assuming the availability of an
appropriate case mix adjuster and a reliable patient information system. These
techniques provide clinicians with tools to help maintain quality in this era of
managed care.
PMID- 9635555
TI - Predicting follow-up functional outcomes in outpatient rehabilitation.
AB - Functional outcomes at an average of six months after outpatient rehabilitation
were investigated in a pilot study with a sample of 42 patients receiving
physical therapy for low back, neck, and other musculoskeletal problems. Logistic
regression analyses were used to study variables related to the achievement of a
predetermined level of physical functioning or to whether improvement occurred
from initial to follow-up assessment. Scales used in the analyses were obtained
from two measures of functioning, the Medical Outcomes Trust Short Form 36 (SF
36) and the Medical Rehabilitation Follow Along (MRFA instrument). Demographic
and program characteristic variables obtained from clinic records were also
included in the analyses. The independent variables entered into two groups of
regression equations included age, gender, presenting problem, workers'
compensation coverage, functioning at initial assessment, number of visits,
length of program, and intensity of program. For the SF-36, the General Health
scale and presenting problem predicted above or below a level greater than one
standard deviation less than the mean on the Physical Functioning scale at follow
up. The combination of the Role Physical and Role Emotional scales predicted
follow-up level on the Physical Component Summary (PCS) scale. The interaction of
age and intensity of treatment was predictive for both the Physical Functioning
and PCS scales. For predicting improvement or no improvement using the SF-36
scales, General Health and the interaction between age and intensity were
predictive of change on the Physical Functioning scale, whereas age and the
interaction between age and number of visits were predictive of change on the PCS
scale. For the MRFA instrument, the interaction between age and the intensity of
treatment was predictive for both a predetermined level of physical functioning
and amount of improvement in physical functioning at follow-up. An intensity
rating of pain and a measure of affective distress at initial assessment both
improved the identification of patients at risk for not reaching a given level of
functioning, whereas treatment intensity improved the identification of those
patients at risk for not showing improvement at follow-up. Length of time between
the end of outpatient therapy and follow-up assessment was generally not related
to follow-up physical functioning. Interpretation and implications of these
findings, as well as applications of this analytic approach to outcomes
assessment, are discussed.
PMID- 9635556
TI - Effectiveness of force application in manual wheelchair propulsion in persons
with spinal cord injuries.
AB - The objective of this study was to investigate effectiveness of force
application, the ratio power output/energy expenditure, and timing parameters of
wheelchair propulsion in persons with tetraplegia (TP, n=17) and paraplegia (PP,
n=12), at two different intensity conditions. All subjects performed a maximal
exercise test on a wheelchair ergometer. Exercise bouts with an intensity of 30
to 50% and 60 to 80% of the maximal power output were analyzed. Effectiveness of
force application, defined as the ratio of the effective force and the total
force, was considerably lower in TP, compared with PP. Effectiveness of force
application in the plane of the wheel was comparable between TP and PP. TP showed
a significantly lower effectiveness of force application in the frontal plane and
applied the forces in a more lateromedial direction to the hand rim. The ratio
power output/energy expenditure, calculated as an indication of gross mechanical
efficiency, was considerably lower in TP and was associated with the
effectiveness of force application (r=0.64; P < 0.01). Timing parameters showed
that TP positioned their hands in a more backward position on the hand rim.
Comparing the different intensity conditions revealed that force was applied more
effectively, and the ratio power output/energy expenditure was higher at the
higher intensity condition. Push time, relative to cycle time, increased, and
beginning angle showed a forward shift with a higher load. TP tended to decrease,
whereas PP showed a tendency for an increase in stroke angle with a higher load.
The low effectiveness and different pattern of force application in TP should be
taken into account when developing other wheelchair propelling mechanisms and
training programs for this population.
PMID- 9635557
TI - Propulsion technique and anaerobic work capacity in elite wheelchair athletes:
cross-sectional analysis.
AB - Wheelchair sports and daily manual wheelchair propulsion are dominated by
frequent short-term power demands. The purpose of the current cross-sectional
study was to determine the variation in propulsion technique in association with
sprint power production among elite wheelchair athletes. Therefore, 67 wheelchair
athletes (different impairments; 17 female and 50 male athletes; age, 29.1+/-7
yr; body weight, 60.7+/-11.8 kg; training hours, 12.9+/-6.4 h x wk(-1); VO2 peak,
1.7+/-0.7 liter x min(-1); aerobic power output, 72.2+/-36.7 W) were studied
during the World Championships and Games for the Disabled in Assen (1990) on
propulsion technique and anaerobic work capacity in a 30-s sprint test on a
computer controlled wheelchair ergometer. Mean power output (P30) (97+/-45.8 W;
range, 8.3-195.3 W) and heart rate (158.6+/-23.6 b x min(-1)) were highly
variable and seemed associated with impairment level: track athletes, classified
in four different functional classes, showed a class-related P30 of 23, 68, 100,
and 138 W for the male athletes (n=38). Sprint power relative to body weight
varied between 0.36 W X kg BW(-1)+/-0.04 and 1.85 W X kg BW(-1)+/-0.43 for the
different subject groups. Propulsion technique in terms of forces applied to the
rim and timing showed significant differences between subject groups for the
majority of parameters studied. Apart from the mediolateral force and the
negative dip at the start of the push phase, the technique parameters were
significantly related to power production. Fraction effective force, the ratio
between the total force vector and the effective force applied to the hand rim,
appeared low on average (especially for subjects with cerebral palsy and those
with a high spinal lesion) but showed a significant correlation with power output
(r=0.5). In general, propulsion technique parameters were related to both
performance and functionality. The number of training hours showed a small but
significant relation with peak power (r=0.31), peak torque (r=0.4), the amount of
work per push (r=0.41) and the total force vector (r=0.31), stressing the role of
training status, next to disability, as important mediating factor in both
propulsion technique as well as performance capacity. No association between
training hours and fraction effective force was seen. It can be concluded that
propulsion technique and performance parameters are highly variable among
wheelchair athletes. Also, propulsion technique is strongly associated with
functionality and training hours and does clearly relate to performance. The
current results on technique and performance and their possible causal
relationship, but also with impairment and sports discipline, must be further
substantiated in a longitudinal study design.
PMID- 9635558
TI - Medical student referral patterns for musculoskeletal disorders.
AB - The purpose of this study was to determine the relationship between medical
student knowledge and exposure to physiatry and the student's referral patterns
for musculoskeletal disorders. Surveys were mailed to senior medical students at
five United States medical schools across the country with a response rate of 26%
(n=191). Five common musculoskeletal and neurologic disorders were presented as
clinical vignettes and the student was asked to assume the role of a primary care
physician and refer the patient to one of eight specialists listed. A section to
assess the student's subjective overall knowledge and exposure to these fields
was also included. Physiatrists received 27% of the referrals for evaluation and
treatment of chronic low-back pain, 3% of the referrals for acute low-back pain,
10% of the referrals for carpal tunnel syndrome, 22% of the referrals for an
industrial medicine injury, and 20% of the referrals for a sports medicine
injury. The frequency of physiatry referrals for three of the five cases was
significantly correlated (P < 0.05) with the student's overall knowledge of
physical medicine and rehabilitation (PM&R). The presence of a department of PM&R
at the student's school, however, did not have a significant impact on the rate
of referrals. The results indicate that senior medical students referral patterns
are strongly influenced by knowledge of PM&R. This suggests that focusing efforts
on increasing this awareness may be an effective means of increasing referrals to
physiatry in the future.
PMID- 9635559
TI - Electromyographic localization of the palmaris brevis muscle.
AB - The palmaris brevis (PB) is the only muscle frequently innervated by the
superficial branch of the ulnar nerve. It is clinically involved in patients with
sensory impairment of the ulnar nerve sparing the deep branch as seen in mild
cases of cyclist or crutch palsy. It is also involved in palmaris brevis spasm
syndrome. A technique is described that makes it possible to localize the PB
distinctly from its neighbors by electromyographic (EMG) pin examination. Methods
include prospective (1) anatomic measurement in 10 cadavers and (2) EMG pin
examination in 12 normal subjects measuring rise time (ms) and RMS voltage output
(microV). Results showed (1) the area of the PB in elderly cadavers was 2.1+/-0.7
x 2.1+/-0.3 cm with a thickness of 0.2+/-.01 cm and (2) in the live subjects, the
muscle could be located with identification of motor unit potentials having a
rise time <1 ms 100% of the time. In conclusion, the PB can be localized for EMG
analysis by using an approach parallel to surface of the palm. Clinically, it
could be a useful complement to diagnose neuropathy involving the superficial
fibers of the ulnar nerve.
PMID- 9635560
TI - Examination of deficits in conceptual reasoning abilities associated with spina
bifida.
AB - This study explores the "higher order" cognitive abilities of conceptual
reasoning, problem solving, mental flexibility, and efficiency in 36 adolescents
with spina bifida. The subjects, age 10 to 23 years, were assessed on a set of
neuropsychological measures, and an individual profile analysis was conducted.
All subjects, regardless of intelligence quotient, evidenced significant
impairments of mental flexibility, efficiency of processing, conceptualization,
or problem-solving ability. Separate data analysis was carried out for subjects
with an average intelligence quotient. Results indicated a high degree of
variability within profiles with at least one area of dysfunction (as determined
by performance less than the 15th percentile) for each subject. This study
demonstrates the need for individual analysis of "higher order" cognitive
functions including conceptual reasoning, problem solving, mental flexibility,
and efficiency of thinking for children who have spina bifida, regardless of
level of lesion or general intelligence level. It is argued that
neuropsychological deficits underlie the "motivational" and academic difficulties
observed often among this population, especially for those with an average
intelligence quotient. These data support the need to assess conceptual abilities
in children with spina bifida and to provide consultation and early intervention
services.
PMID- 9635561
TI - Measuring frailty in the hospitalized elderly: concept of functional homeostasis.
AB - Functional homeostasis is the ability of an individual to withstand illness
without loss of function. We investigate whether the level of functional
homeostasis predicts adverse outcomes in the 6 months posthospital discharge in
older men and women. A prospective cohort study was conducted in an acute care
geriatric inpatient unit of a university hospital. Subjects included a
consecutive series of patients admitted to the unit. The Functional Independence
Measure (FIM) instrument was used to assess patients at four time points:
preillness, hospital admission, hospital discharge, and 6 months postdischarge.
Of the 122 subjects available for analysis, 64 (52%) experienced a decline in
functional level from preillness to hospital discharge and were defined as having
poor functional homeostasis, whereas 58 (48%) experienced no change or an
increase in functional status and were defined as having good functional
homeostasis. Those with poor functional homeostasis had a higher 6-month
readmission rate to the hospital (59.4 v 39.7%; P=0.03) and a higher rate of any
adverse outcome (78.1 v 50%; P=0.001) than those with good functional
homeostasis. In logistic regressive analyses, functional homeostasis remained a
significant and powerful predictor of adverse outcomes independent of actual
level of function at discharge, age, gender, living status, and other factors
that might influence outcomes. Change in functional status associated with an
acute illness is an independent predictor of adverse outcomes and, in this study,
a better predictor than actual level of function at discharge. Functional
homeostasis is one approach to the quantification of the important but elusive
concept of frailty in the elderly.
PMID- 9635562
TI - Diagnosis of a C-2 fracture during physiatric consultation: a case report.
AB - Consultation in the acute care setting allows physiatrists to make significant
contributions. In our case, a 90-year-old woman presented to the emergency room
after falling down five stairs. Six view C-spine films taken at that time
revealed no fracture. She was sent home on anti-inflammatory medication and was
later admitted for gastritis. A repeat six-view C-spine series again revealed no
fracture. Physiatry was then consulted to prescribe modalities and therapies for
"cervical strain." On examination, the patient demonstrated severely decreased
neck range of motion limited by pain, with pain radiating down her right arm.
Physiatry recommended obtaining a C-spine magnetic resonance image to rule out
occult fracture or herniated disc before proceeding with therapies. The magnetic
resonance image revealed a complex C-2 fracture consisting of a Type III odontoid
component. Computed tomographic scan was then performed to obtain a high
resolution assessment of the bony architecture. The computed tomographic scan
revealed a high degree of comminution, including bilateral pedicle fractures and
a fracture through the left transverse foramen of C-2. The patient was placed in
a hard cervical collar and seen by a neurosurgeon. Had therapies been initiated
before physiatric consultation, the patient could have experienced significant
neurologic complications, including the possibility of becoming tetraplegic. This
case demonstrates that physiatrists play a crucial role in the evaluation of
acute care patients before the initiation of therapies. The authors will review
pertinent history and the results of physical and diagnostic tests.
PMID- 9635563
TI - Cost-effectiveness of venous thrombosis prophylaxis after ischemic stroke.
PMID- 9635565
TI - Fibrillation potentials and positive sharp waves.
PMID- 9635564
TI - Are transition year programs obsolete because of proposed changes in graduate
medical education funding?
PMID- 9635566
TI - Biological properties of recombinant alpha-interferons: 40th anniversary of the
discovery of interferons.
AB - IFNs were first described as potent antiviral agents 40 years ago, and
recombinant IFN-alpha2a and IFN-alpha2b were approved for the treatment of hairy
cell leukemia just 11 years ago. Today, alpha-IFNs are approved worldwide for the
treatment of a variety of malignancies and virologic diseases. Although the exact
mechanism of action of IFN-alpha in the treatment of such diseases is not fully
understood, many advances have been made in the characterization of the
physicochemical and diverse biological properties of this highly pleiotropic
cytokine. Here we review recent developments in our understanding of the
antiviral and immunoregulatory properties of IFN-alpha, the nature of the
multisubunit IFN-alpha receptor, and the molecular mechanisms of signal
transduction. Where available, we have included comparative data on recombinant
alpha-IFNs derived from both naturally occurring and nonnaturally occurring
synthetic genes. We also review clinical data and data on the side effects and
antigenicity of different sources of recombinant alpha-IFNs in humans. These
latter topics are of clinical interest, because they may potentially affect the
efficacy of these various products. Hopefully, what is already known about IFN
will prompt further exploration into the mechanism(s) of action of IFN-alpha and
thus deliver new applications for this prototypic cytokine, whose full
therapeutic potential is yet to be realized.
PMID- 9635567
TI - Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.
AB - Mutation and deletion of the PTEN tumor suppressor gene occurs in about 40% of
endometrial carcinomas. The purpose of this study was to determine whether PTEN
mutations also are present in endometrial hyperplasias, which are premalignant
precursors of invasive endometrial adenocarcinomas. Genomic DNA from 51
endometrial hyperplasias was extracted from paraffin blocks, and PCR was used to
amplify the nine exons of the PTEN gene. These products were screened using
single-strand conformation analysis, and variant bands were sequenced. Somatic
mutations in the PTEN gene were seen in 10 of 51 cases (20%), and two mutations
were found in one case. An identical 4-bp deletion in exon 8 was seen in three
cases, and 8 of 11 PTEN mutations predicted truncated protein products. There was
no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6
of 32; 19%) relative to those without atypia (4 of 19; 21%). These data suggest
that inactivation of the PTEN tumor suppressor gene is an early event in the
development of some endometrial cancers.
PMID- 9635568
TI - Apoptosis and perturbation of cell cycle progression in an acidic environment
after hyperthermia.
AB - The effects of an acidic environment on the induction of apoptosis by 42 degrees
C hyperthermia were investigated. An acidic environment (pH 6.6) enhanced the
hyperthermia-induced apoptosis in HL-60 human promyelocytic leukemia cells as
judged by the DNA fragmentation, flow cytometric analysis of DNA content, and
cleavage of poly(ADP-ribose) polymerase. Hyperthermia exerted no effect on the
expression of Bcl-2 and Bax, regardless of the environmental acidity during
heating. The time of increase in apoptosis after heating coincided with the time
of decrease in the G1-phase cell population. It seemed that the increase in heat
induced apoptosis in HL-60 cells in an acidic environment was due to a direct
increase in the proteolytic cleavage of poly(ADP-ribose) polymerase by acidic
caspases without the involvement of Bcl-2 and Bax, and that heat-induced
apoptosis occurred during G1 phase in HL-60 cells.
PMID- 9635569
TI - Genetic vaccination against the melanocyte lineage-specific antigen gp100 induces
cytotoxic T lymphocyte-mediated tumor protection.
AB - Melanocyte lineage-specific antigens, such as gp100, have been shown to induce
both cellular and humoral immune responses against melanoma. Therefore, these
antigens are potential targets for specific antimelanoma immunotherapy. A novel
approach to induce both cellular and humoral immunity is genetic vaccination, the
injection of antigen-encoding naked plasmid DNA. In a mouse model, we
investigated whether genetic vaccination against the human gp100 antigen results
in specific antitumor immunity. The results demonstrate that vaccinated mice were
protected against a lethal challenge with syngeneic B16 melanoma-expressing human
gp100, but not control-transfected B16. Both cytotoxic T cells and IgG specific
for human gp100 could be detected in human gp100-vaccinated mice. However, only
adoptive transfer of spleen-derived lymphocytes, not of the serum, isolated from
protected mice was able to transfer antitumor immunity to nonvaccinated
recipients, indicating that CTLs are the predominant effector cells. CTI, lines
generated from human gp100-vaccinated mice specifically recognized human gp100.
Interestingly, one of the CTL lines cross-reacted between human and mouse gp100,
indicating the recognition of a conserved epitope. However, these CTLs did not
appear to be involved in the observed tumor protection. Collectively, our results
indicate that genetic vaccination can result in a potent antitumor response in
vivo and constitutes a potential immunotherapeutic strategy to fight cancer.
PMID- 9635570
TI - Mapping of ER gene CpG island methylation-specific polymerase chain reaction.
AB - Southern analysis has shown that DNA from 25% of primary estrogen receptor (ER)
alpha-negative breast tumors displays aberrant methylation at one site within the
ER gene CpG island. To examine more sites and increase sensitivity, we developed
a methylation-specific PCR assay to map methylation of the entire ER CpG island.
The island was unmethylated in normal breast tissue and ER-positive breast cancer
cell lines, but extensively methylated in all ER-negative cell lines and breast
tumors examined. In addition, some of the ER-positive/progesterone receptor
negative and ER-positive/progesterone receptor-positive tumors (about 70% and
35%, respectively) displayed methylation of the ER CpG island, suggesting that
this heterogeneity within tumor cell populations could potentially shed light on
the etiology of ER-negative recurrent tumors arising from ER-positive tumors.
PMID- 9635571
TI - Beta-catenin mutations in human prostate cancer.
AB - Beta-catenin plays essential roles in both intercellular adhesion and signal
transduction. As a signaling molecule, beta-catenin supplies an activating domain
to the T-cell factor/lymphoid enhancer-binding factor family of DNA-binding
proteins and activates gene transcription. Posttranslational stabilization of
beta-catenin, leading to elevated protein levels and constitutive gene
activation, has been proposed as an important step in oncogenesis. Stabilization
of beta-catenin can occur through mutation to highly conserved amino acids
encoded in exon 3 of the beta-catenin gene (CTNNB1). To determine whether this
pathway of malignant transformation is important in prostate cancer, we analyzed
104 prostate cancer tissue specimens, 4 prostate cancer cell lines, and 3
prostate tumor xenografts for activating mutations in exon 3 of CTNNB1. Mutations
were detected in 5 of the 104 prostate cancer tissue samples. Four of the five
mutations involved serine or threonine residues implicated in the degradation of
beta-catenin. A fifth tumor had a mutation at codon 32, changing a highly
conserved aspartic acid to a tyrosine. Mutational analysis of multiple regions
from several tumor samples showed that the beta-catenin mutations were present
focally and therefore may occur during tumor progression.
PMID- 9635572
TI - Activation of the beta-catenin gene in primary hepatocellular carcinomas by
somatic alterations involving exon 3.
AB - We screened 75 primary hepatocellular carcinomas for somatic mutations in the
entire coding region of the beta-catenin gene. We detected somatic mutations in
14 tumors; 12 were considered to cause amino acid substitutions and 2 were
interstitial deletions of 51 or 195 nucleotides of genomic DNA, corresponding to
exon 3. Among the 12 point mutations, 6 occurred at potential serine/threonine
phosphorylation residues of codons 33, 41, or 45. The remaining six tumors
contained a mutation at codon 32 (aspartic acid) or 34 (glycine), flanking to the
serine residue at codon 33. By Western blot analysis, we confirmed accumulation
of beta-catenin in five tumors for which frozen tissues were available; the five
included tumors in which amino acid alterations had occurred at codons 32, 34, or
45, and one with a 17-amino acid deletion. Our results suggested that
accumulation of beta-catenin due to amino acid substitutions at potential
serine/threonine phosphorylation residues or at their neighboring codons or
interstitial deletions involving exon 3 could contribute to hepatocellular
carcinogenesis.
PMID- 9635573
TI - Cell motility of tumor cells visualized in living intact primary tumors using
green fluorescent protein.
AB - Metastasis is the leading cause of death in cancer patients. Cell motility is
believed to be a necessary step in the metastatic process (L. Liotta and W. G.
Stetler-Stevenson, In: Cancer: Principles and Practice of Oncology, pp. 134-149,
1993). Currently, most methods available to study the behavior of metastatic
tumor cells are indirect, e.g., cell motility is examined in vitro and the
results are correlated with metastatic capability (A. W. Partin, et al., Cancer
Treat. Res., 59: 121-130, 1992). We have developed a model that directly examines
the motility of metastatic primary tumor cells in situ. A metastatic rat breast
cancer cell line was established that constitutively expresses green fluorescent
protein. Upon s.c. injection of these cells into the mammary fat pad of female
Fischer 344 rats, primary and metastatic tumors form that fluoresce when they are
excited with FITC-filtered light. Animations of metastatic tumor cells moving in
live rats were generated by intravital imaging of the primary tumor in situ on a
laser scanning confocal microscope. With this model, the behavioral phenotype of
metastatic and nonmetastatic tumor cells can be described and determined. This
information will allow the effects of genetic manipulations or therapeutic
treatments on this phenotype to be determined (D. R. Soll, Int. Rev. Cytol., 163:
43-104, 1995). This is the first time that living primary tumor cells in a live
animal have been visualized as part of a clinically relevant model.
PMID- 9635575
TI - Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific
antigen.
AB - New approaches to target cytotoxic therapy specifically to metastatic prostate
cancer sites are urgently needed. As such an approach, an inactive prodrug was
synthesized by coupling the primary amine of doxorubicin to the COOH-terminal
carboxyl of a seven-amino acid peptide carrier (i.e., Mu-His-Ser-Ser-Lys-Leu-Gln
Leu). The seven-amino acid peptide was documented to be hydrolyzable specifically
by the serine protease prostate-specific antigen (PSA) to liberate the active
cytotoxin L-leucyl-doxorubicin. Primary cultures of PC-82 human prostate cancer
cells secreted high levels of enzymatically active PSA (i.e., 70 +/- 5 ng of
enzymatically active PSA/10(6) cells/24 h), whereas LNCaP human prostate cancer
cells produced lower levels of enzymatically active PSA (i.e., 2.3 +/- 1 ng/10(6)
cells/24 h). LNCaP cells, however, secreted sufficient amounts of enzymatically
active PSA to activate the doxorubicin prodrug to a cytotoxic form in vitro. The
specificity of the cytotoxic response to the prodrug was demonstrated by the fact
that 70 nM of the prodrug killed 50% of the PSA-producing LNCaP cells, whereas
doses as high as 1 microM had no cytotoxic effect on PSA-nonproducing TSU human
prostate cancer cells in vitro.
PMID- 9635574
TI - Allelic deletion analysis of the FHIT gene predicts poor survival in non-small
cell lung cancer.
AB - The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor
suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head
and neck. Reports of frequent allelic deletion and abnormal transcripts in
primary lung tumors plus recent evidence that it is targeted by tobacco smoke
carcinogens suggest that it plays an important role in lung carcinogenesis. Non
small cell lung carcinoma still maintains a poor 5-year survival rate with the
stage of disease at presentation as a major determinant of prognosis. We examined
for allelic deletion at the FHIT locus in a series of 106 non-small cell lung
carcinomas for which a full clinical, epidemiological, and 5-year survival
profile was available. We found an allelic deletion frequency of 38% at one or
two intragenic microsatellites. Allelic deletion of FHIT was related to tumor
histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity
(LOH) compared with 12 of 22 (55%) nonadenocarcinomas (P = 0.03). We found that
63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26%
with LOH had wild type p53 negative sequence (P = 0.02). We also found a
significant trend toward poorer survival in patients with LOH of at least one
locus of the FHIT gene (log rank, P = 0.01). This survival correlation is
independent of tumor stage, size, histological subtype, degree of
differentiation, and p53 mutation status. Our data support the hypothesis that
the loss of the FHIT contributes to the molecular pathogenesis of human lung
cancer and is an indicator of poor prognosis.
PMID- 9635576
TI - Enhanced binding of antibodies to the DTR motif of MUC1 tandem repeat peptide is
mediated by site-specific glycosylation.
AB - The epithelial mucin MUC1 is an important tumor marker of breast cancer and other
carcinomas. Its immunodominant DTR motif, which is the principal target for
immunotherapeutic approaches, has been assumed until recently not to be
glycosylated in both normal and tumor MUC1 and to acquire its immunogenic
conformation by virtue of a certain number of tandem repeats. We present evidence
that the antigenicity of the single repeat toward a considerable number of
antibodies to the DTR motif is greatly enhanced if it is glycosylated within this
motif, and only in this position. Twenty-eight monoclonal anti-MUC1 antibodies
with DTR specificity were tested for binding to synthetic 21-mer (AHG21) or 20
mer (HGV20) tandem repeat peptides O-glycosylated with galactose beta1-3N
acetylgalactosamine alpha or N-acetylgalactosamine alpha at defined Thr or Ser
positions. Binding was measured in ELISA experiments using the glycopeptides as
plate-immobilized antigens or as inhibitors in solution. At least 12 antibodies
revealed significantly enhanced binding to the peptides glycosylated at the DTR
motif (Thr-10) as compared to positional isomers glycosylated at Thr-5, Ser-6,
Ser-16, or Thr-17 and to the nonglycosylated peptides. Six antibodies (VU-3-C6,
A76-A/C7, Ma552, VU-11-D1, VU-12-E1, and VU-11-E2) that were unreactive with the
monomeric repeat peptide did bind to the DTR-glycosylated peptide. Several lines
of evidence suggest that glycosylation with N-acetylgalactosamine is sufficient
for the observed enhancement effect. Our results are of special interest in
conjunction with the recent observation that the DTR motif of lactation
associated MUC1 is O-glycosylated in vivo (Muller et al., J. Biol. Chem., 272:
24780-24793, 1997). They may have consequences for the design of efficient tumor
vaccines.
PMID- 9635577
TI - Citrus auraptene exerts dose-dependent chemopreventive activity in rat large
bowel tumorigenesis: the inhibition correlates with suppression of cell
proliferation and lipid peroxidation and with induction of phase II drug
metabolizing enzymes.
AB - In our previous short-term experiment, Citrus auraptene inhibited the development
of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions
for colorectal carcinoma. In the present study, the possible inhibitory effect of
dietary administration of auraptene was investigated using an animal colon
carcinogenesis model with a colon carcinogen AOM. Male F344 rats were given s.c.
injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce colon
neoplasms. They also received diets containing 100 or 500 ppm auraptene for 4
weeks in groups of "initiation" feeding, starting 1 week before the first dosing
of AOM. The diets containing auraptene were also given to rats for 38 weeks in
groups of "postinitiation" feeding. At the termination of the study (38 weeks),
dietary administration of auraptene caused dose-dependent inhibition in AOM
induced large bowel carcinogenesis. Auraptene feeding during the initiation phase
reduced the incidence of colon adenocarcinoma by 49% at 100 ppm (P = 0.099) and
65% at 500 ppm (P = 0.0075). Auraptene administration during the postinitiation
phase inhibited the incidence of colon adenocarcinoma by 58% at 100 ppm (P =
0.021) and 65% at 500 ppm (P = 0.0075). Also, the multiplicity of colon carcinoma
was significantly reduced by initiation feeding at a dose level of 500 ppm (P <
0.01) and postinitiation feeding at a level of 100 and 500 ppm (P < 0.05 and P <
0.01, respectively). Feeding of auraptene suppressed the expression of cell
proliferation biomarkers (ornithine decarboxylase activity and polyamine content)
in the colonic mucosa and reduced the production of aldehydic lipid peroxidation
[malondialdehyde and 4-hydroxy-2(E)-nonenal]. In addition, auraptene increased
the activities of Phase II drug-metabolizing enzymes (glutathione S-transferase
and quinone reductase) in the liver and colon. These findings suggest that the
inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the
initiation level might be associated, in part, with increased activity of Phase
II enzymes, and those at the postinitiation stage might be related to suppression
of cell proliferation and lipid peroxidation in the colonic mucosa.
PMID- 9635578
TI - Tumorigenicity of sodium ascorbate in male rats.
AB - Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and
bicarbonate, produces urinary alterations when fed at high doses to rats, which
results in mild superficial urothelial cytotoxicity and regeneration but not
tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low
incidence of bladder tumors in rats if administered in a two-generation bioassay.
In the present study, we evaluated sodium ascorbate in a two-generation bioassay
that involved feeding to the male and female parental F344 rats for 4 weeks
before mating, feeding the dams during gestation and lactation, and then feeding
the weaned (at 28 days of age) male F1 generation rats for the remainder of their
lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and
7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an
increase in urinary bladder urothelial papillary and nodular hyperplasia and the
induction of a few papillomas and carcinomas. There was a dose-responsive
increase in renal pelvic calcification and hyperplasia and inhibition of the
aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the
short-term urothelial effects of sodium ascorbate in rats are inhibited by
treatments producing urinary acidification to pH < 6.0, we coadministered high
doses of long-term NH4Cl to groups of rats with 5.0 or 7.0% sodium ascorbate to
evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus
2.78% NH4Cl in the diet was toxic, and the group was terminated early during the
course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl
showed complete inhibition of the urothelial effects of sodium ascorbate and
significant inhibition of its renal effects. We also demonstrated the presence of
a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate
at all doses, in a dose-responsive manner. The formation of the precipitate was
inhibited by coadministration with NH4Cl. The proliferative effects of sodium
ascorbate on the male rat urinary tract in this study are similar to those seen
with sodium saccharin when administered in a two-generation bioassay. Mechanistic
information suggests that this is a high-dose, rat-specific phenomenon.
PMID- 9635579
TI - Potent inhibition of hemangioma formation in rats by the acyclic nucleoside
phosphonate analogue cidofovir.
AB - The acyclic nucleoside phosphonate analogue cidofovir elicited a marked
protection against hemangioma growth in newborn rats that had been infected i.p.
with a high titer of murine polyomavirus. Untreated, infected rats developed
cutaneous, i.m., and cerebral hemangiomas associated with severe hemorrhage and
anemia leading to death within 3 weeks postinfection (p.i.). s.c. treatment with
cidofovir at 25 mg/kg, once a week, resulted in a complete suppression of
hemangioma development and associated mortality when treatment was initiated at 3
days p.i. (100% survival compared with 0% for the untreated animals). Cidofovir
still afforded 40% survival and a significant delay in tumor-associated mortality
when treatment was started at a time at which cerebral hemangiomas were already
macroscopically visible (i.e., 9 days p.i.). Infectious virus or viral DNA was
undetectable in the brain at different times p.i. as assessed by means of (a) a
DNA-DNA hybridization assay and (b) titration of the brain for infectious virus
content, indicating that there was no viral replication in murine polyomavirus
infected rats. Moreover, a semiquantitative PCR for viral protein 1 DNA revealed
that the amount of viral protein 1 DNA declined with time after infection to
become virtually undetectable at 18 days p.i. Therefore, an antitumor or
antiangiogenic effect, rather than inhibition of viral replication, may be the
reason for the inhibitory activity of cidofovir in this model. Cidofovir may thus
be further explored for the treatment of vascular tumors and, in particular, life
threatening juvenile hemangiomas.
PMID- 9635580
TI - Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin
activated by glutathione S-transferase.
AB - TER286 is a latent drug activated by human glutathione S-transferase (GST)
isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609
human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human
breast carcinoma, selected for resistance to cyclophosphamide, both showed
increased sensitivity to TER286 over their parental lines in parallel with
increased expression of GST P1-1. In primary human tumor clonogenic assays, the
spectrum of cytotoxic activity observed for TER286 was both broad and unusual
when compared to a variety of current drugs. In murine xenografts of M7609
engineered to have high, medium, or low GST P1-1, responses to TER286 were
positively correlated with the level of P1-1. Cytotoxicity was also observed in
several other cell culture and xenograft models. In xenografts of the MX-1 human
breast carcinoma, tumor growth inhibition or regression was observed in nearly
all of the animals treated with an aggressive regimen of five daily doses. This
schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to
60% of control and was no worse than for a single dose of TER286. These studies
have motivated election of TER286 as a clinical candidate.
PMID- 9635581
TI - Purification and characterization of a Mg2+-dependent endonuclease (AN34) from
etoposide-treated human leukemia HL-60 cells undergoing apoptosis.
AB - An important biochemical hallmark of apoptosis is the cleavage of chromatin into
oligonucleosomal fragments. Here, we purified a Mg2+-dependent endonuclease from
etoposide-treated HL-60 cells undergoing apoptosis. High levels of Mg2+-dependent
endonuclease activity were detected in etoposide-treated HL-60 cells, and this
activity increased in a time-dependent manner following etoposide treatment. Such
an activity could not be detected in untreated cells or in cells treated with
etoposide in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
(OMe)-fluoromethyl ketone (zVAD-fmk) or the serine protease inhibitor tosyl-L
phenylalanine chloromethyl ketone (TPCK). This Mg2+-dependent endonuclease was
purified by a series of chromatographic procedures. The enzyme preparation showed
a single major protein band with Mr 34,000, determined by SDS-PAGE. The presence
of the Mr 34,000 Mg2+-dependent endonuclease was also confirmed by activity gel
analysis. The enzyme required only Mg2+ for full activity. pH optimum was in the
range of 6.5-7.5. This enzyme introduced single- and double-strand breaks into
SV40 DNA and produced internucleosomal DNA cleavage in isolated nuclei from
untreated cells. The DNA breaks were terminated with 3'-OH, consistent with
characteristic products of apoptotic chromatin fragmentation. We propose to
designate this Mr 34,000 Mg2+-dependent endonuclease AN34 (apoptotic nuclease Mr
34,000).
PMID- 9635582
TI - Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety
of recombinant methioninase.
AB - The elevated exogenous-methionine dependency of tumors for growth has been
observed in all major cancer cell types. We have previously cloned a methioninase
(rMETase) from Pseudomonas putida to deplete methionine. Growth inhibition
followed by apoptotic cell death was induced by treatment of tumor cells with
rMETase in vitro. A single i.p. injection of 300 units of rMETase can lower the
serum methionine level in the mice from 70 microM to less than 1 microM within 2
h and maintain this depleted level for 8 h. Repeated dosing of rMETase of tumor
bearing mice could be administered without acute immune-hypersensitivity. rMETase
treatment demonstrated growth inhibitory activity against human tumors in nude
mice, including those which were multiple drug-resistant. No body weight loss or
hematotoxicity, except a slight anemia, was found throughout the therapy. The
combined treatment of the Lewis lung carcinoma with a fixed rMETase dose and
increasing doses of 5-fluorouracil (5-FU) resulted in a dose-dependent enhanced
antitumor efficacy for survival as well as tumor growth inhibition. Thus,
methionine depletion by rMETase potentiates the antitumor efficacy of 5-FU. The
data presented in this report thus indicate that rMETase is active alone, is
synergistic in combination with 5-FU, and has negligible toxicity suggesting a
novel clinical approach for effective cancer therapy.
PMID- 9635583
TI - Preferential cytotoxicity of cells transduced with cytosine deaminase compared to
bystander cells after treatment with 5-flucytosine.
AB - In vitro experiments from our laboratory and others have suggested that herpes
simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy depends on
gap junctional intercellular communication (GJIC) to produce a strong bystander
effect. Furthermore, we have shown that cells transduced with HSV-TK can be
protected from GCV-mediated toxicity by GJIC with bystander cells. We wished to
determine whether GJIC affected either the bystander or protective effect of the
cytosine deaminase (CD)/5-flucytosine (5-FC) gene therapy approach, in which CD
converts 5-FC to 5-fluorouracil (5-FU). To test this, we designed a coculture
system using communication-competent WB rat hepatocytes and a noncommunicating
subclone (aB1), which were transduced with CD and with antibiotic resistance
genes so that we could independently determine the survival of the CD-containing
or bystander cells. We found that, compared to the HSV-TK/GCV strategy, bystander
killing resulting from treatment with CD/5-FC does not depend on GJIC. However,
our most striking finding was that both communication-competent and -incompetent
CD-transduced cells were preferentially killed, by a factor of up to 500,
compared to bystander cells. The lesser dependence of the CD/5-FC system on GJIC,
combined with the finding that most cancer cells lack the capacity for GJIC,
suggest that the CD/5-FC system may be superior to the HSV-TK/GCV approach for
gene therapy. However, the premature death of the CD-transduced 5-FU "factory"
suggests that other strategies may be necessary to produce a sufficient quantity
of 5-FU for a duration long enough to produce permanent tumor regression.
PMID- 9635584
TI - Differential inhibition of fluid accumulation and tumor growth in two mouse
ascites tumors by an antivascular endothelial growth factor/permeability factor
neutralizing antibody.
AB - In the accompanying paper (Luo et al., Cancer Res., 58: 2652-2660, 1998), we
demonstrated that vascular endothelial growth factor (VEGF), also designated
vascular permeability factor (VPF), significantly accumulated in all mouse
malignant ascites tested, suggesting its fundamental role in ascites tumors.
Removal of VEGF may inhibit the development of ascites tumors. In this study,
using a goat antimouse VEGF-neutralizing antibody, we tested this hypothesis with
two well-defined syngeneic mouse ascites tumors: MM2 breast adenocarcinoma and
OG/Gardner lymphoma 6C3HED (expressing moderate and low levels of VEGF,
respectively). This antibody significantly inhibited MM2 and OG cell-free ascites
fluid-induced hyperpermeability of mouse peritoneal microvessels and in vitro
endothelial cell growth. Mice bearing tumors were administered i.p. daily with
the antibody or normal goat IgG as controls for 8 days, at doses of 20-fold (for
MM2-bearing mice) or 40-fold (for OG-bearing mice) the estimated amounts of VEGF
that kinetically accumulated in the ascites fluid after the tumor inoculation.
The average volume of ascites fluid, number of tumor cells and leaked RBCs, and
the peritoneal microvessel permeability in MM2-bearing mice that received the
antibody treatment were significantly lower than those in the matched controls (P
< 0.01). Unexpectedly, OG-bearing mice did not show satisfactory response to the
anti-VEGF treatment. This discrepancy was not likely due to inadequate doses or
different host immune responses, but it was quite possibly to the different
characteristics of MM2 carcinoma and OG lymphoma tumors, the latter being
strongly invasive, and/or the existence of an inflammatory mediator(s), such as
bradykinin or cytokine(s) other than VEGF. In summary, our results directly
demonstrated, for the first time, differential roles for VEGF in ascites tumors
in vivo and suggest the potential of VEGF inhibition as a specific therapy for
ascites tumors of carcinoma origin, which are the major cause of the malignant
ascites in adult humans.
PMID- 9635585
TI - Targeting p53 for adoptive T-cell immunotherapy.
AB - p53 gene mutations occur in most human cancers and result in an altered protein
product that accumulates within the cell. Although the observed endogenous human
CTL response to p53 is weak, high-affinity, human p53-specific CTLs have been
generated from HLA A2.1 transgenic mice immunized with human CTL epitope
peptides. In this study, we examine the ability of HLA A2.1-restricted and human
p53-specific CTLs from HLA A2.1 transgenic mice to suppress the growth of p53
overexpressing human tumors in severe combined immunodeficient (SCID) mice. In
vitro, murine p53(149-157)-specific CTLs selectively lysed the p53-overexpressing
pancreatic carcinoma cell line Panc-1 but did not recognize HLA A2.1- tumor cells
or HLA A2.1+ normal human fibroblasts. Furthermore, in vivo, the growth of
established human tumor xenografts in SCID mice was significantly reduced and
survival was prolonged after the administration of p53-specific CTLs but not
after the administration of control CTLs or PBS alone. Following treatment with
p53(149-157)-specific CTLs, regressing Panc-1 tumors were infiltrated by the CD8+
CTLs, as demonstrated by immunohistochemistry. These findings suggest that
p53(149-157)-specific and HLA A2.1-restricted murine CTLs suppress the growth of
established Panc-1 tumors following adoptive transfer into SCID hosts and prolong
their survival.
PMID- 9635586
TI - Epitope mapping of a series of human thymidylate synthase monoclonal antibodies.
AB - We have reported previously the development and application of several monoclonal
antibodies to thymidylate synthase (TS). In this study, we used a series of
overlapping 17-mer peptides that spanned the entire TS protein to map the epitope
recognized by three TS monoclonal antibodies (TS 106, TS 109, and TS 110). Using
an ELISA, we identified two peptides (R126-F142 and L131-R147) that bound all
three antibodies, which suggests that each antibody recognized a similar epitope
on TS. A second set of peptides, representing sequential single-residue
truncations from either the amino terminus or the carboxyl terminus starting with
a G129-E145 17-mer, was synthesized. A 10-amino acid sequence P133-F142
(PVYGFQWRHF) was identified as the binding epitope for all three antibodies.
Further investigation via substitution mutational analysis of each residue within
this epitope revealed that residues F137, W139, R140, H141, and F142 were
critical for maximal binding of TS 106 and TS 110. TS 109 showed a similar
pattern except in regard to R140, with which there was no apparent loss of
binding. In addition to the utility of the three antibodies in detecting and
measuring TS levels, identification of the binding locus permits the potential
application of these antibodies in the investigation of TS enzymatic and
regulatory function.
PMID- 9635587
TI - Aminosyn II effectively blocks renal uptake of 18F-labeled anti-tac disulfide
stabilized Fv.
AB - Because intact IgG has limitations as a tumor-imaging agent, radiolabeled Fv
fragments are being evaluated. Due to the high renal accumulation of Fv
fragments, methods to block renal uptake are being sought. This study evaluated
how well Aminosyn II, a Food and Drug Administration-approved 15% amino acid
solution, would block the renal accumulation of 18F anti-Tac disulfide-stabilized
Fv (dsFv) fragments (small fragments with high renal uptake). The anti-Tac dsFv
is directed against the alpha subunit of the interleukin 2 receptor. It was
labeled at specific activities of 1.1-2.7 mCi/mg using N-succinimidyl 4
[18F]fluoromethyl benzoate. Four adult baboons were injected i.v. with 0.7-1.9
mCi and 150 microg of dsFv. Each baboon was preinjected with Aminosyn II i.v.
and, on a separate occasion, with a control solution. Thirty min before injection
of 18F-labeled anti-Tac dsFv, a bolus of either solution was given, followed by a
constant infusion of 13.3 ml/kg/h. Quantitative positron emission tomography
imaging was performed. The amino acid levels in serum were measured serially. The
baseline levels of lysine (and other amino acids) in plasma were not
significantly different in either the Aminosyn II or control infusion group and
did not change during the control infusion. In the Aminosyn II group, lysine
levels in plasma 5 min before anti-Tac dsFv infusion were 5-15 times higher than
the baseline value and continued to rise during the infusion. The areas under the
curve in blood of the 18F-labeled anti-Tac dsFv, from time of injection to end of
imaging, expressed as percentage injected dose (%ID), were 28.94 +/- 4.05%ID x
h/liter (mean +/- SD) for the control group and 32.09 +/- 11.15%ID x h/liter for
the Aminosyn II group (P = 0.54). The peak concentration of 18F-labeled anti-Tac
dsFv in the kidney of the controls was 24.53 +/- 4.34%ID; the value in the
Aminosyn II group was 5.39 +/- 1.89%ID, representing a mean decrease of 78.5%.
The times to reach 90% of the peak levels of 18F in the kidney were 5.6 +/- 3.0
min for the Aminosyn II group and 33.8 +/- 4.8 min for the control group. The
amounts excreted in urine by 90 min were 47.7 +/- 8.55%ID and 78.5 +/- 12.8%ID (P
= 0.01) for the controls and Aminosyn II group, respectively. In conclusion,
Aminosyn II effectively blocks the renal accumulation of 18F-labeled anti-Tac
dsFv. Use of Aminosyn II should allow much higher tracer administration for the
same radiation exposure to the target organ (kidney).
PMID- 9635588
TI - Frequent loss of heterozygosity on the long arm of chromosome 6: identification
of two distinct regions of deletion in childhood acute lymphoblastic leukemia.
AB - Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified
nonrandom chromosomal abnormalities of the long arm of chromosome 6. Most of the
alterations are deletions that are thought to be indicative of the presence of a
tumor suppressor gene that is mutated on the remaining allele. These observations
led us to consider whether 6q loss may contribute to the pathogenesis of
childhood ALL. To define further a region containing this gene, we analyzed the
loss of heterozygosity (LOH) of chromosome 6 in 113 primary ALL samples with
matched normal DNA using 34 highly informative microsatellite markers. LOH was
found in 17 (15%) samples at one or more of the loci, and partial or interstitial
deletions of 6q were detected in 11 of these tumors. On the basis of these
results, we performed a detailed deletional map and identified two distinct
regions of deletion. The first region is flanked by D6S283 and D6S302 loci at
6q21-22. The second region is flanked by D6S275 and D6S283 loci at 6q21. Clinical
analysis determined that LOH of 6q was demonstrated both in precursor-B cell ALLs
(15 of 93; 16%) and in T cell ALLs (2 of 19; 11%). In addition, 19 patients have
been studied at diagnosis and relapse; 18 showed the same 6q21-22 structural
abnormality at relapse (normal, 16 patients; LOH, 2 patients) as their initial
presentation, suggesting, albeit with a small patient sample size, that 6q21-22
deletions may be an initial event in leukemogenesis and may occur less frequently
during the progression of childhood ALL. These data suggest the presence of
putative tumor suppressor genes on chromosome arm 6q that are important in the
development of both T and precursor-B childhood ALLs. Our map provides important
information toward cloning putative ALL tumor suppressor genes.
PMID- 9635589
TI - Disruption of the cyclin D/cyclin-dependent kinase/INK4/retinoblastoma protein
regulatory pathway in human neuroblastoma.
AB - The p16INK4a (MTS1) and pl8INK4c gene products are normal, and highly expressed,
in human neuroblastoma cell lines. The retinoblastoma protein (pRb) was,
nonetheless, phosphorylated and functional in these cells. Such high levels of
p16INK4a/p18INK4c should normally inhibit cyclin-dependent kinase (CDK) 4 and 6
activities in cells containing functional pRb, delaying cell cycle progression
and growth. These neuroblastoma cell lines express both CDK4 and CDK6 mRNA and
protein, but only significant CDK6 protein kinase activity was detected in this
study. In addition, CDK6 was not present in p16INK4a immune complexes in cells
with significant kinase activity, although p16INK4a levels were high. Others have
shown that a specific mutation in the NH2-terminal region of the CDK4 gene
product can disrupt p16INK4a binding, thereby bypassing its inhibitory activity.
To determine whether mutation of the CDK6 gene, or some other mechanism, is
responsible for the CDK6 kinase activity in these cell lines, several
complementary analyses were performed. The CDK6 gene from each cell line was
examined for mutations that might affect p16INK4a binding, whereas p16INKa add
back experiments were performed with CDK6 immune complexes to assess p16INK4a
function. A bona fide CDK6 mutation that disrupts p16INK4a binding and prevents
inhibition of CDK6 protein kinase activity was identified in 1 of 17
neuroblastoma cell lines. The mechanism(s) responsible for disruption of p16INK4a
inhibitory activity in the remaining cell lines is unknown, but these results
suggest that neuroblastoma cells may bypass the cell cycle block imposed by
constitutive expression of wild-type p16INK4a in novel ways.
PMID- 9635590
TI - Cigarette smoke induces DNA deletions in the mouse embryo.
AB - Cigarette smoking causes cancer and DNA mutations. However, long-term chronic
exposure to smoke is believed to be necessary for carcinogenesis. Here, we
investigate the relationship between short-term exposure to smoke and the
frequency of deletions in the mouse embryo. Deletions and other genome
rearrangements are associated with carcinogenesis and inheritable diseases. The
pink-eyed unstable (p(un)) mutation in the C57BL/6J mouse is the result of
internal duplication of 70 kb of DNA within the p gene. Spontaneous reversion
events in homozygous p(un)/p(un) mice occur by deletion of one copy of the
duplicated sequence. Reversion events occurring in the embryonic premelanocytes
of the developing fetus give rise to black spots on the gray fur of the offspring
after birth. We investigated the effects of exposure of pregnant p(un) mice to
cigarette smoke and cigarette smoke condensate (CSC) on the frequency of black
spots occurring in the offspring. Pregnant dams were exposed (whole body) to
smoke generated by either filtered or unfiltered cigarettes for 4 h, or
alternatively, mice were given a 15 mg/kg dose of CSC during their 10th day of
gestation. TPM, CO concentration, and plasma nicotine and cotinine levels were
determined to characterize the smoke exposure. There was a significant increase
in the number of DNA deletions in the embryo as evidenced by spotted offspring in
both smoke-exposed groups and in the CSC group. These results suggest that
embryos are highly sensitive to the genotoxic activity of cigarette smoke
following a single exposure of only 4 h.
PMID- 9635591
TI - The G2 block induced by DNA damage: a caffeine-resistant component independent of
Cdc25C, MPM-2 phosphorylation, and H1 kinase activity.
AB - Treatment of cells with agents that cause DNA damage often results in a delay in
G2. There is convincing evidence showing that inhibition of p34cdc2 kinase
activation is involved in the DNA damage-induced G2 delay. In this study, we have
demonstrated the existence of an additional pathway, independent of the p34cdc2
kinase activation pathway, that leads to a G2 arrest in etoposide-treated cells.
Both the X-ray-induced and the etoposide-induced G2 arrest were associated with
inhibition of the p34cdc2 H1 kinase activation pathway as judged by p34cdc2 H1
kinase activity and phosphorylation of cdc25C. Caffeine treatment restored these
activities after either of the treatments. However, the etoposide-treated cells
did not resume cycling, revealing the presence of an alternative pathway leading
to a G2 arrest. To explore the possibility that this additional pathway involved
phosphorylation of the MPM-2 epitope that is shared by a large family of mitotic
phosphoproteins, we monitored the phosphorylation status of the MPM-2 epitope
after DNA damage and after treatment with caffeine. Phosphorylation of the MPM-2
epitope was depressed in both X-ray and etoposide-treated cells, and the
depression was reversed by caffeine in both cases. The results indicate that the
pathway affecting MPM-2 epitope phosphorylation is involved in the G2 delay
caused by DNA damage. However, it is not part of the caffeine-insensitive pathway
leading to a G2 block seen in etoposide-treated cells.
PMID- 9635592
TI - Isolation and partial characterization of a cDNA encoding a rabbit liver
carboxylesterase that activates the prodrug irinotecan (CPT-11).
AB - We have isolated a cDNA encoding a rabbit carboxylesterase (CE; EC 3.1.1.1) that
converts the camptothecin-derived prodrug irinotecan (CPT-11) to the potent
topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin. NH2-terminal amino acid
sequencing of a purified rabbit CE allowed the design of redundant
oligonucleotides to perform PCR from rabbit liver cDNA. DNA sequencing of the PCR
product confirmed the identity of the clone, and after both 5' and 3' rapid
amplification of cDNA ends, oligonucleotide primers were designed to amplify the
entire cDNA. The 1698-bp open reading frame encoded a 565-amino acid protein
containing the characteristic CE B-1 and B-2 motifs, a hydrophobic NH2-terminal
leader sequence, and the COOH-terminal residues HIEL that are thought to be
responsible for protein localization in the endoplasmic reticulum. Transient
expression of the cDNA in COS-7 cells resulted in CE activity in cell extracts
and increased the sensitivity of cells to CPT-11. Additionally, stable expression
of the rabbit liver CE cDNA in the human glioma U-373 MG cell line resulted in a
56-fold decrease in the IC50 value for CPT-11, whereas the expression of a human
alveolar macrophage cDNA encoding a highly homologous CE produced no change in
drug sensitivity.
PMID- 9635593
TI - Significant expression of vascular endothelial growth factor/vascular
permeability factor in mouse ascites tumors.
AB - Vascular endothelial growth factor (VEGF), also known as vascular permeability
factor, is believed to be a potent mediator of peritoneal fluid accumulation and
angiogenesis and of tumor growth in ascites tumor. Such roles, however, have not
been generally established because of insufficient quantitative and systemic
analyses. To address this, we examined the expression of VEGF in 13 mouse ascites
tumors (5 sarcomas, 3 carcinomas, 2 lymphomas, 1 leukemia, 1 mastocytoma, and 1
plasmacytoma). Using a newly developed sensitive and specific radioreceptor
binding assay and functional assays, we found that active VEGF was significantly
accumulated (6-850 ng/ml) in the ascites fluids of all 13 tumors. VEGF
concentrations are higher in the tumors of sarcoma and carcinoma origin (430.4 +/
234.2 ng/ml) than in those of lymphoma and hematological tumor origin (19.2 +/-
10.45 ng/ml). VEGF that accumulated in the peritoneal fluids or expressed in the
ascites tumor cells was easily visualized with immunoprecipitation Western blot
analysis with a rough correlation to the expression levels of VEGF gene in these
tumor cells, suggesting that the tumor cells, at least in part, contributed to
the production of the VEGF that accumulated in the ascites fluid. Most ascites
tumors expressed VEGF; the 164-amino acid isoform was predominant, the 120-amino
acid isoform was less abundant, and the 188-amino acid isoform was least
abundant. Several representative ascites tumors expressed similar, if not higher,
levels of VEGF when they were cultured at normoxic states, suggesting that they
expressed VEGF at high levels in a constitutive manner. The microvessel densities
in the peritoneal walls of tumor-bearing mice, which are significantly higher
than those in normal mice, basically correlated to but did not parallel the VEGF
concentrations in their respective ascites fluids. Thus, a complicated
relationship may exist between the VEGF production and angiogenesis associated
with ascites tumor in vivo. Taken together, our observations suggest that VEGF
plays a fundamental role in ascites tumor formation; however, its importance may
vary according to tumor origin.
PMID- 9635594
TI - Systemic treatment with a recombinant erbB-2 receptor-specific tumor toxin
efficiently reduces pulmonary metastases in mice injected with genetically
modified carcinoma cells.
AB - Receptor-mediated targeted tumor therapy is an important applied consequence of
the studies on the genetic causes of cancer. These therapy concepts have to be
evaluated in novel animal models that reflect the molecular aberrations found in
human tumors. Here we introduce an animal model that allows the evaluation of
drugs directed against a surface receptor that is frequently altered in primary
human adenocarcinomas. Tumor toxins are polypeptides in which a tumor cell
specific recognition domain and a toxic effector domain have been joined by DNA
recombination in vitro. Tumor cell recognition is contributed by a single-chain
antibody domain specific for the extracellular domain of the erbB-2 receptor
[scFv(FRP5)] and cytotoxicity by the enzymatically active domain of a bacterial
exotoxin (exotoxin A from Pseudomonas aeruginosa). The erbB-2 receptor is
overexpressed in many primary human cancer cells and is a favorable target for
directed tumor therapy. The fusion protein scFv(FRP5)-exotoxin A has previously
been shown to be able to efficiently and specifically kill erbB-2 receptor
expressing tumor cells. We have investigated the potential of this tumor toxin to
detect and eliminate metastasizing tumor cells upon systemic administration.
Murine renal carcinoma cells genetically modified with human erbB-2 receptor and
bacterial beta-galactosidase genes form large pulmonary metastases when injected
into the tail vein of BALB/c mice. Administration of the tumor toxin over a 10
day time period starting 1 day after tumor cell transplantation totally
suppressed the formation of metastases. The treatment of animals 11 days after
tumor cell transplantation, allowing the establishment of many pulmonary
metastases, led to a drastic reduction in their number and size.
PMID- 9635595
TI - Expression and secretion of neuroleukin/phosphohexose isomerase/maturation factor
as autocrine motility factor by tumor cells.
AB - The results obtained from fragmented protein microsequencing have suggested that
autocrine motility factor (AMF), a tumor-secreted Mr 55,000 cytokine that
regulates cell motility in vitro as well as invasion and metastasis in vivo, is
the neuroleukin (NLK)/phosphohexose isomerase (PHI)/maturation factor (MF)
polypeptide. Here, we cloned, sequenced, and studied the expression, secretion,
and distribution of AMF/NLK/PHI/MF in neoplastic and their normal counterpart
cells. Although both normal and neoplastic cells express the gene product,
overexpression associated with selective secretion of the protein was observed
only in tumor cells. The cDNA sequences of AMF/NLK/PHI/MF found in both human
cancer and normal cells were found to be identical, suggesting that its secretion
by neoplastic cells is independent of mutation or alternative splicing.
Immunohistochemical visualization has depicted AMF/NLK/PHI/MF to be localized
into tubular-like vesicles, diffusely distributed throughout the cytoplasm and
not colocalized with any particular cytoskeletal network. Confocal microscopic
imaging had shown a partial colocalization between AMF and its receptor (Mr
78,000 glycoprotein), especially on the malignant cell surface periphery. The
results suggest that extracellular AMF activity may be a result of the product of
intracellular cleavage of a precursor polypeptide, which is overexpressed and
selectively secreted through a nonclassical secretory mechanism by neoplastic
cells.
PMID- 9635596
TI - Genetic modulation of neu proto-oncogene-induced mammary tumorigenesis.
AB - Modulation of oncogene-induced carcinogenesis by secondary mutation or genetic
background may be an important factor in determining the expression of the tumor
phenotype. We have investigated the role of loss of function mutations and strain
specific genetic elements in the modulation of oncogene-induced breast cancer
using a murine model. FVB female mice transgenic for the rat neu proto-oncogene
[mouse mammary tumor virus (MMTV)-neu] developed mammary tumors between 7 and 12
months of age, whereas FVB x C57Bl/6 (F1) MMTV-neu mice had tumor latencies
greater than 18 months. The expression level of the neu transgene was equivalent
in tumor tissue from both FVB and F1 mice. Furthermore, increased tumor latency
did not appear to be associated with a decrease in expression of the neu
transgene in the normal mammary gland of F1 mice because immunohistochemical
staining for neu expression in the mammary glands of 3-month-old virgin female
mice revealed similar levels of protein expression in FVB and F1 animals. When F1
animals were backcrossed one generation onto the FVB strain ([FVB x B6] F1 x
FVB), a subset of the resulting offspring developed tumors with a latency
equivalent to that of the pure-strain FVB mice. Statistical analysis of the
genetic variability in mammary tumor latency indicated that approximately three
independent genes were involved in the latency effect. Interestingly, when tumor
growth rates were compared in these same animals, F1 mice had significantly
faster tumor growth rates compared with FVB mice.
PMID- 9635597
TI - Antiapoptotic effect of ectopic TAL1/SCL expression in a human leukemic T-cell
line.
AB - Aberrant expression of TAL1 occurs frequently in human T-cell acute lymphoblastic
leukemia. The effect of TAL1 expression in the T-cell lymphoid precursor,
however, remains unclear. In the current study, we have developed TAL1 stable
transfectants in a human immature T-cell lymphoid cell line. Whereas no effect on
proliferation, cell culture density, or cell cycle was detected, the
transfectants were more resistant than the parental cell line to apoptosis
induced by chemotherapeutic agents including etoposide, daunorubicin,
doxorubicin, cytosine arabinoside, methotrexate and vincristine and also to
apoptosis induced by Fas/CD95 cross-linking. This effect was independent of the
cytostatic effects of the drugs. The basic domain-deleted transfectants did not
demonstrate altered sensitivity, suggesting that DNA binding was necessary for
resistance to apoptosis. The ability to alter the response to a wide range of
cell death-inducing stimuli suggests that TAL1 acts at a late stage of the
apoptotic cascade. These data therefore provide direct evidence of an
antiapoptotic effect of ectopic TAL1 expression in response to cytotoxic agents,
thus providing insight into its oncogenic function in T-cell acute lymphoblastic
leukemia and a novel experimental model to further investigate the underlying
mechanisms. These data also have potential practical significance for cytotoxic
therapy of this disorder.
PMID- 9635598
TI - Effects of GLP-1 on gastric emptying, antropyloric motility, and transpyloric
flow in response to a nonnutrient liquid.
AB - Glucagon-like polypeptide 1 (GLP-1) may be a major enterogastrone, slowing
gastric emptying when released by intestinal nutrients. In six conscious dogs, we
studied the effects of GLP-1, on antropyloric motility, gastric emptying, and
transpyloric flow after instillation of 500 ml of saline into the stomach. The
meal was given and recordings were started 15 min after intravenous bolus and
infusion of either saline or three different doses of GLP-1. Intravenous GLP-1
produced a dose-related retardation of gastric emptying associated with a
decrease in the number and volume of flow pulses in comparison to saline. This
change in transpyloric flow was associated with an inhibition of antropyloric
pressure waves, a stimulation of isolated pyloric pressure waves, and an increase
in basal pyloric tone induced by intravenous GLP-1 infusion. Our findings show
that GLP-1 has a potent dose-dependent inhibitory effect on transpyloric flow and
gastric emptying. This effect is temporally associated with inhibition of antral
"pumping" and stimulation of pyloric "braking" mechanisms.
PMID- 9635599
TI - Relationships between gastric emptying and intestinal absorption of nutrients and
energy in mini pigs.
AB - Little is known about the relationship between gastric emptying of nutrients
regulated by feedback mechanisms and the absorptive capacity of the gut.
Therefore, we wanted to elucidate these interrelationships. A 150-cm jejunal
segment was perfused (1-8 kcal/min) with three different nutrient solutions
(either 60% of energy as carbohydrate, or 60% as protein, or 33.3% of each
nutrient). In separate experiments, gastric emptying was measured after
administration of three different meals with the same nutrient composition as the
perfusion solutions. The jejunal absorption of carbohydrate, protein, fat, and
energy demonstrated saturation kinetics. The kinetics differed among the three
nutrients; carbohydrates were absorbed at higher rates than fat and protein.
Interactions among the nutrients altered the kinetics providing a constant
absorption of energy. After meals, the stomach emptied equal amounts of energy
despite large variations in meal composition. The available intestinal absorptive
capacity for protein was utilized by 96%, whereas that for carbohydrate, fat and
energy were utilized only by 46-62%. Besides reserves in the absorptive capacity,
the intestine provided reserves in total length available for absorption. The
results indicate a close relationship between the energy-dependent absorption of
nutrients and the energy-dependent feedback inhibition of gastric emptying.
PMID- 9635600
TI - Role of gastric emptying in functional dyspepsia: a scintigraphic study of 94
subjects.
AB - Many physiological factors can alter gastric emptying, and the role of gastric
emptying in functional dyspepsia is controversial. The aim of this study was to
assess the effects of different factors (age, sex, the degree of dyspeptic and
irritable bowel symptoms, lactase deficiency, smoking habits, the use of
antiinflammatory drugs, and H. pylori gastritis) on gastric emptying in patients
with functional dyspepsia. The study population consisted of 83 patients with
functional dyspepsia and 11 control subjects who underwent a standardized
scintigraphic examination to study gastric emptying. This study detected no
difference in gastric emptying between different subgroups with functional
dyspepsia. There was, however, a slight tendency for delayed gastric emptying
among patients with functional dyspepsia compared to controls. Intragastric
distribution of the solid content was more distally located in smokers, and the
solid lagtime was prolonged among antiinflammatory drug users. The gastric
emptying of liquids was delayed among older patients. The subgrouping of
dyspeptic symptoms is of minor importance with respect to gastric emptying.
Habitual smoking and the use of antiinflammatory drugs are potent factors able to
alter the gastric emptying of solids, but the role of H. pylori seems to be less
important.
PMID- 9635601
TI - Transient impact of hemodialysis on gastric myoelectrical activity of uremic
patients.
AB - Upper gastrointestinal discomforts are common in uremic patients. Investigators
have stressed the structural, histopathological, and physiological changes in the
gastrointestinal tract in the past decades. Few data are available about the
electrophysiological changes in the stomach of uremic patients. It is not known
whether hemodialysis alters gastric myoelectrical activity. More interestingly,
what is the long-term effect? To address these questions, we measured gastric
myoelectrical activity before and after hemodialysis in patients with end-stage
renal disease on maintenance dialysis treatment. Twenty-one uremic patients with
dyspeptic complaints were enrolled in this study. Gastric myoelectrical activity
was measured noninvasively using abdominal surface electrodes
(electrogastrography). The paired variables obtained before and after
hemodialysis were compared statistically. We also compared the difference between
two subgroups defined as new hemodialysis patients and chronic hemodialysis
patients. We found that there was a significantly lower percentage of normal slow
wave frequency obtained after hemodialysis in comparison with before hemodialysis
(fasting state: 49.1 +/- 4.8% vs 68.1 +/- 5.4%, P < 0.01; fed state: 53.8 +/-
6.9% vs 73.4 +/- 4.1%, P < 0.01). In comparing the subgroups, there were no
differences between each EGG variable. We concluded that the hemodialysis itself
compromised gastric myoelectrical activity in its immediate effect. However,
there were no permanent effects regarding gastric myoelectrical activity itself.
PMID- 9635602
TI - Effect of capsaicin-containing red pepper sauce suspension on upper
gastrointestinal motility in healthy volunteers.
AB - Afferent nerves play a major role in the regulation of gastrointestinal motility.
The questions remains if specific food ingredients can selectively activate such
fibers. The aim of the study was to investigate the effect of intraesophageal
application of a capsaicin-containing red pepper sauce (Tabasco) suspension on
upper gastrointestinal motility in a controlled trial. After a baseline recording
[esophageal motility, balloon distension, electrogastrogram (EGG)], red pepper or
saline solution was infused intraesophageally in seven healthy volunteers. At 30
min gastric emptying and orocecal transit time were determined using a
[13C]acetate and H2-lactulose breath test. Infusion of red pepper sauce
suspension significantly increased the amplitudes (65.8 +/- 3 to 78.5 +/- 4.7 mm
Hg, P < 0.05) and propagation velocity (2.9 +/- 0.3 to 4.25 +/- 0.3 sec, P <
0.05) of esophageal pressure waves and LES pressure (17.8 +/- 1.4 to 23.7 +/- 2.6
mm Hg, P < 0.05). It significantly decreased perception and discomfort threshold
of intraesophageal balloon distension, reduced the percentage of normal
electrical activity in the EGG, and delayed gastric emptying (saline: T(1/2) 42.9
+/- 12.0 min vs red pepper: T(1/2) 66.8 +/- 19.0 min, P < 0.05). Despite the
prolongation of gastric emptying, orocecal transit time was not altered,
indicating an actual increase of intestinal transit. Esophageal application of
capsaicin-containing red pepper sauce suspension had profound changes on upper
gastrointestinal motility, which could improve clearance and protection of the
esophagus and could lead to retention of the irritant in the stomach and faster
transit through the small bowel.
PMID- 9635603
TI - Double-blind, placebo-controlled study on effects of diclofenac sodium and
indomethacin on postprandial gastric motility in man.
AB - Data from animal studies suggest that NSAIDs-induced gastric damage may be due to
increased gastric motility. Such a mechanism, however, has never been tested or
demonstrated in man. We evaluated the effects of two frequently prescribed
NSAIDs, indomethacin and diclofenac sodium, on postprandial gastric motor
activity (a physiologically reproducible stimulus) in healthy volunteers to see
whether these compounds increase gastric motility. Twenty-four healthy volunteers
of both sexes, 21-35 years of age, underwent a basal gastric motility recording.
Thereafter, they were randomized in three groups to receive either placebo,
indomethacin (50 mg three times a day) or diclofenac sodium (50 mg three times a
day) for a week. At the end of the week, they underwent an identical manometric
study. Analysis of the motility tracings showed no difference in gastric antral
motility index and in amplitude of gastric antral contractions after NSAIDs with
respect to the basal study and to the placebo group. About 50% of subjects (two
in the placebo group) complained of side effects. These were transient and mild,
except in two subjects taking indomethacin, in whom endoscopy was necessary; one
of these had a small prepyloric ulcer. It is concluded that in man NSAID-related
gastric damage is unlikely to be due to increased gastric motility.
PMID- 9635604
TI - Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in
orthotopic lung transplant patients.
AB - Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm.
Previously they have not been described in lung transplant recipients. We report
a high incidence of symptomatic giant gastric ulcers and identify the risk
factors for ulcer development in these patients. We examined the records of all
95 patients who had undergone lung transplantation at our institution from
November 1991 to July 1995. Fourteen of the patients who underwent lung
transplantation developed symptoms that required esophagogastroduodenoscopy.
Three of these patients (21%) were found to have giant gastric ulcers. The
relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy
after lung transplantation is over 40 times that of population controls. The
patients who developed giant gastric ulcers, despite H2 antagonist use, had all
received bilateral lung transplantation and had received nonsteroidal
antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids.
The risk of developing giant gastric ulcers is significantly increased in
patients who have undergone bilateral orthotopic lung transplantation. Clinicians
should be made aware of this complication in order to avoid use of ulcerogenic
medications in this population. Avoidance of these medications could potentially
minimize the risk of this complication.
PMID- 9635605
TI - Effectiveness of lamivudine in treatment of acute recurrent hepatitis B after
liver transplantation.
PMID- 9635606
TI - Oral ganciclovir usage for cytomegalovirus prophylaxis in organ transplant
recipients: is emergence of resistance imminent?
PMID- 9635607
TI - Optical biopsy in human pancreatobiliary tissue using optical coherence
tomography.
AB - Optical coherence tomography (OCT) is a new technique for performing high
resolution, cross-sectional tomographic imaging in human tissue. OCT is analogous
to ultrasound B mode imaging except that it uses light rather than acoustical
waves. As a result, OCT has over 10 times the resolution of currently available
clinical high-resolution cross-sectional imaging technologies. In this work, we
investigate the capability of OCT to differentiate the architectural morphology
of pancreatobiliary tissues. Normal pancreatobiliary tissues, including the
gallbladder, common bile duct, pancreatic duct, and pancreas were taken
postmortem and imaged using OCT. Images were compared to corresponding histology
to confirm tissue identity. Microstructure was delineated in different tissues,
including tissue layers, glands, submucosal microvasculature, and pancreatic
islets of Langerhans. The ability of OCT to provide high-resolution imaging of
pancreatobiliary architectural morphology suggests the feasibility of using OCT
as a powerful diagnostic endoscopic imaging technology to image early stages of
pancreatobiliary disease.
PMID- 9635608
TI - Adenomyoma of the distal common bile duct mimicking cholangiocarcinoma.
PMID- 9635609
TI - Human proximal duodenal alkaline secretion is mediated by Cl-/HCO3- exchange and
HCO3- conductance.
AB - The proximal duodenal epithelium secretes bicarbonate into an adherent mucus
layer, thereby protecting the mucosa from injury by gastric acid and pepsin.
While bicarbonate secretion is stimulated and inhibited by a number of agonists
and antagonists, the apical anion transport pathways have not been addressed
fully. The objective was to assess if apical Cl-/HCO3- exchange and Cl-:HCO3-
conductance are involved in duodenal mucosal bicarbonate secretion (DMBS). In
healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with
either saline or 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate
secretion and transepithelial potential difference (PD) were stimulated by either
PGE2 or the phosphodiesterase inhibitor theophylline to increase cyclic AMP.
Luminal DIDS abolished PGE2-stimulated DMBS, yet had no effect on the increase in
PD and failed to significantly alter theophylline-induced DMBS and PD. Therefore,
in human proximal duodenum, it appears that PGE2 and cAMP activate distinct HCO3-
transport pathways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS
insensitive HCO3- conductance.
PMID- 9635610
TI - Identification of H. pylori in saliva by a nested PCR assay derived from a newly
cloned DNA probe.
AB - A novel probe was developed from genomic DNA of Helicobacter pylori ATCC type
strain 43629. It hybridized with all 73 H. pylori clinical isolates tested but
not with any of 183 non-H. pylori DNAs in dot blot hybridization. Typing tests
revealed 41 different HaeIII-digestion patterns from 57 H. pylori strains tested.
Based on the sequence of the probe, a nested PCR was developed that detected as
little as 2 fg of H. pylori DNA or approximately equivalent to one cell. No PCR
products were amplified from any of 21 non-H. pylori strains tested. Using this
nested PCR, H. pylori DNA was detected in 33 of 45 (73%) saliva samples collected
from patients with gastric H. pylori infection. These data suggest that the probe
is useful for typing H. pylori and that the nested PCR is a valuable tool for
detecting H. pylori DNA in saliva.
PMID- 9635611
TI - Helicobacter pylori infection and peptic ulcer disease in cirrhosis.
AB - An increased frequency of peptic ulcer disease is noted in patients with
cirrhosis, but the role of H. pylori in this disorder remains to be determined.
The diagnosis of cirrhosis was confirmed by a combination of clinical,
biochemical, radiological, and histological methods. The severity of cirrhosis
was assessed by Pugh's modification of Child's criteria. Upper gastrointestinal
endoscopy was performed consecutively to evaluate the presence of varices and
gastroduodenal mucosa. H. pylori status was assessed by histology, urease test,
and serology. In all, 130 patients with cirrhosis were recruited into the study;
there were 86 males and 44 females with a mean (SD) age of 54.4 (12.7) years. The
H. pylori prevalence was 76.2%. There was no difference in age between the H.
pylori-positive and -negative cirrhotics (P = 0.29). The H. pylori prevalence
revealed no difference among cirrhotics with Child A (77.8%), Child B (72.9%),
and Child C (78.6%) (P = 0.8), and neither was there a difference in H. pylori
prevalence in cirrhotics with and without congestive gastropathy (77% vs 73.7%, P
= 0.84). The prevalence of H. pylori in cirrhotics with and without varices did
not show a statistical difference (75% vs 81.8%, P = 0.68). There also was no
difference in the H. pylori prevalence between cirrhotic patients with and
without peptic ulcers (84.4% vs 69.7%, P = 0.09). In conclusion, the prevalence
of H. pylori or peptic ulcer is independent of the severity of cirrhotic liver
disease. The association between H. pylori infection and peptic ulcer disease is
weak in cirrhosis.
PMID- 9635612
TI - Beneficial effects of Helicobacter pylori eradication on idiopathic chronic
urticaria.
AB - Helicobacter pylori, the most important cause of gastritis and peptic ulcer,
recently has been associated with several extradigestive diseases. The aim of
this study was to assess the prevalence of Helicobacter pylori infection and the
effects of bacterium eradication in 42 consecutive patients affected by
idiopathic chronic urticaria. Helicobacter pylori was assessed by [13C]urea
breath test. Amoxicillin, clarithromycin, and lansoprazole were given to infected
patients for seven days. Urticaria and gastrointestinal symptoms were assessed on
enrollment and after eradication. Fifty-five percent of patients proved to be
infected by Helicobacter pylori. Prevalence of gastrointestinal symptoms did not
differ between infected and uninfected patients. Eighty-eight percent of infected
patients in whom the bacterium was eradicated after therapy showed a total or
partial remission of urticaria symptoms. Conversely, symptoms remained unchanged
in all uninfected patients. In conclusion, Helicobacter pylori affects a high
percentage of patients with idiopathic chronic urticaria; however, typical
gastrointestinal symptoms do not identify infection status. Bacterium eradication
is associated with a remission of urticaria symptoms, suggesting a possible role
of Helicobacter pylori in the pathogenesis of this skin disorder.
PMID- 9635613
TI - In vitro wound repair by human gastric fibroblasts: implications for ulcer
healing.
AB - Fibroblasts modulate epithelial biological activities and play a key role in the
ulcer healing process. There is no information regarding the biological response
of human gastric fibroblasts to regulatory compounds. The aim of this study was
to assess the effects of growth factors and prostaglandins on an in vitro model
of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were
used to study proliferative responses, determined by [3H]thymidine incorporation
into DNA. In vitro wound repair was determined in confluent fibroblast monolayers
after mechanical denudation. The presence of putative growth factors secreted by
fibroblasts was studied in conditioned medium by heparin-affinity chromatography
and immunodetection with specific antibodies. Serum and platelet-derived growth
factor (PDGF) -BB induced a dramatic increase in both gastric fibroblast
proliferation and closure of wounded cell monolayers, whereas these activities
were inhibited by both transforming growth factor (TGF) -beta1 and prostaglandin
E1. Basal activities in unstimulated gastric fibroblasts were lower than those
obtained in skin fibroblasts. Conditioned medium stimulated fibroblast
proliferation and wound repair activity, which was inhibited by the addition of
suramin, and was partially dependent on the presence of PDGF-like factor. PDGF is
a major, autocrine promotor of human gastric fibroblast-dependent wound repair
activities, which are inhibited by prostaglandins and TGF-beta. These findings
might be important for future therapeutic ulcer healing approaches.
PMID- 9635614
TI - Treating nonulcer dyspepsia considering both functional disorders of the
digestive system and psychiatric conditions.
AB - Nonulcer dyspepsia (NUD) is a common syndrome, but the optimal treatments have
yet to be established. This study was performed to determine the most effective
treatment for NUD. Subjects were recruited through the Department of General
Internal Medicine at the Kyushu University Hospital because of their somatic
symptoms. When no organic lesions were found, the patients were directed to
consult our department (Psychosomatic Medicine); 194 consecutive NUD patients
were studied. All subjects were assessed psychiatrically with the Structured
Clinical Interview for DSM-III-R(SCID). Patients with serious NUD were
hospitalized, and randomly divided into control (N = 42) and experimental groups
(N = 86). The controls were treated with physical treatment alone. The
experimental group received psychiatric treatment in addition, based on the
results of SCID. The experimental group showed a significant improvement compared
with the controls (P < 0.0001). The treatment for NUD taking into consideration
both the physical and psychiatric conditions is highly effective.
PMID- 9635615
TI - Histological study of mechanisms of adaptive cytoprotection on ethanol-induced
mucosal damage in rat stomachs.
AB - Adaptive cytoprotection in the gastric mucosa could be induced by exposure to low
concentrations of noxious agents. However, experimental results reported so far
were based on macroscopic studies. We aimed to investigate the phenomenon of
gastric adaptive cytoprotection of mild irritants and its correlation with
intramucosal mucus at the histological level. It was found that histological
damage induced by ethanol had a negative correlation with the length of the mucus
secreting layer in the gastric mucosa. Mild irritants such as 20% ethanol and 5%
NaCl preserved the 100% ethanol-induced intramucosal mucus depletion, but only
the former agent demonstrated a cytoprotective effect against the histological
damage, indicating that preservation of intramucosal mucus may not necessarily
play a permissive role in adaptive cytoprotection. The capsaicin-sensitive
sensory afferent neurons, sensory chemoreceptors, muscarinic receptors, alpha2
adrenoceptors and peripheral dopamine D2-receptors were found to be the
components of the autonomic nervous system involved in the cytoprotective
processes of 20% ethanol. Endogenous mediators including nitric oxide,
prostaglandins, and possibly nonprotein sulfhydryl compounds also seemed to
participate in such protection. Nevertheless, 0.3 M HCl did not show any effect
either on mucosal damage or depletion of intramucosal mucus induced by absolute
ethanol. These findings suggest that only 20% ethanol shows histological
cytoprotection, which would involve various components of the autonomic nervous
system and endogenous mediators. Furthermore, this investigation also implies a
new perspective: that in order to study a true adaptive cytoprotection,
histological examination of the gastric mucosa should be performed.
PMID- 9635616
TI - Adenosine protects against indomethacin-induced gastric damage in rats.
AB - This study examines the putative gastroprotective effect of adenosine on
indomethacin-induced gastric lesions and the possible mechanisms involved. After
24 hr of starvation, the rats were treated either with indomethacin (Indo; 25
mg/kg, subcutaneously) alone or adenosine + Indo (Ado; 7.5 mg/kg, subcutaneously,
three times a day), or the vehicle (5% NaHCO3, subcutaneously). The length of
hemorrhagic lesions in the stomachs was expressed as the lesion index. The tissue
associated myeloperoxidase (MPO) activity and protein oxidation were measured in
gastric tissue samples. Formation of reactive oxygen species in gastric tissues
was measured by using luminol- and lucigenin-enhanced chemiluminescence. In other
groups of rats, gastric mucosal permeability and gastric acid output were
performed following the same treatment regimens. The gastric mucosal permeability
was measured by determination of [51Cr]EDTA clearance in a perfused stomach
preparation and gastric acid secretion studies were performed following pylorus
ligation. The lesion index, the increase in lucigenin-enhanced chemiluminescence,
and the increase in gastric mucosal permeability in Indo-treated rats were
reversed by Ado pretreatment. Ado pretreatment also prevented the increase in
gastric acid output and gastric volume in Indo-treated rats. Thus, these findings
implicate that exogenous adenosine has a protective role on indomethacin-induced
gastric lesions, possibly by inhibiting gastric hyperacidity and reactive oxygen
formation and by preventing disruption of the mucosal integrity.
PMID- 9635617
TI - Mechanism of enhancement of intestinal ulcerogenicity of S-aryl propionic acids
by their R-enantiomers in the rat.
AB - We previously observed a marked increase in gastrointestinal toxicity of rac
flurbiprofen compared to the therapeutically equivalent dose of the S enantiomer.
This paper quantitates these observations and examines the mechanism by which
this paradoxical toxicity occurs. We have evaluated the ulcer scores, mucosal
neutrophil infiltration, by immunostaining of CD11/18 antigen, and mucosal
neutrophil activity by myeloperoxidase measurement at two dose levels of (R)-,
(S)-, and rac-flurbiprofen, administered over 30 days. Dose-response for
intestinal ulcer production was observed for rac- and (S)-flurbiprofen; animals
given (R)-flurbiprofen exhibited no ulcers. Yet rac-flurbiprofen proved to be
twice as ulcerogenic as (S)-flurbiprofen. The mechanism of the exacerbation of
gastrointestinal toxicity of (S)-flurbiprofen by the noncyclooxygenase inhibiting
(R)-flurbiprofen is believed to be associated with its effect on ICAM-1 up
regulation. This is followed by neutrophil adhesiveness to ICAM-1 via the LFA-1
antigen on its surface and the extravasation of neutrophils into the tissue. We
also examined the effect of high dose (R)-flurbiprofen vs vehicle over 15 days in
animals in which ulcers had been produced by treatment with (S)-flurbiprofen for
the previous 15 days. (R)-flurbiprofen did not sustain induced ulcers. The
results of this study suggest that human studies be conducted to determine if
enhanced gastrointestinal toxicity occurs in man. This is at issue since rac
compounds of this class are available over the counter and others may be
introduced.
PMID- 9635618
TI - Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of
Oddi motility in Australian brush-tailed possum.
AB - The neural distribution and action of gastrin-releasing peptide in the
extrahepatic biliary tree of the Australian brush-tailed possum was investigated.
Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing
peptide-containing nerves throughout the neural plexuses of the gallbladder,
sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide
(5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced
by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin
insensitive. Sphincter of Oddi motility and transsphincteric flow were not
altered. Possible mediation of the gallbladder response by gastrin was examined.
Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder
motility to 64% of that produced by gastrin-releasing peptide, and did not alter
sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing
nerves are found in the neural plexus of the possum extrahepatic biliary tree.
Gastrin-releasing peptide induces gallbladder contraction in part by a direct
action on gallbladder smooth muscle and also via release of gastrin.
PMID- 9635619
TI - Gallstone prevalence in Germany: the Ulm Gallbladder Stone Study.
AB - The Ulm Gallbladder Stone Study is the first ultrasound-based epidemiologic
survey of cholecystolithiasis in the former West Germany. A study population of
1116 blood donors (656 men, age 38.0 +/- 12.0 years; 460 women, age 34.1 +/- 11.2
years) at the Central Blood Bank of the German Red Cross in Ulm was examined
between April 1994 and February 1995. Based on age, subjects were assigned to one
of four groups (18-30, 31-40, 41-50, and 51-65 years). Following a structured
interview of each study subject, an ultrasound examination was carried out and a
blood sample obtained for laboratory study. Overall, 6.0% (95% (95% CI: 4.8%
7.6%) of all study subjects (5.8% of the men and 6.3% of the women) exhibited
evidence of current or past gallbladder disease (cholelithiasis or history of
cholecystectomy). The prevalence of gallbladder disease correlated positively
with age, reaching a maximum of 13.7% (9.5-20.0) in the 51- to 65-year-old age
group, and also correlated as with body mass index (BMI). Female subjects with
previous full-term pregnancies showed a higher prevalence of cholelithiasis, but
this difference was not statistically significant for age-adjusted analysis.
Subjects with a family history of cholelithiasis were found to suffer from
gallstones in 11.5% (8.0-16.7) of cases compared with 4.6% (3.4%-6.3%) of
subjects without such family history. Autopsy studies conducted in Germany have
shown the prevalence of gallstones to be about 13.1% in men and 33.8% in women.
Our sonographic data are relatively low in comparison. This may be due, in part,
to the specific selection characteristics inherent in retrospective autopsy
studies, such as age distribution and the presence of other pathologic factors
associated with increased risk for cholelithiasis. The Ulm data rank in the lower
third of the prevalence range reported for European sonographic studies to date.
Age, positive family history, and increased BMI all correlated positively with
the prevalence of gallbladder disease (P < 0.05). For the study population as a
whole, there was no gender-specific increased risk for the development of
gallstones.
PMID- 9635620
TI - Adjuvant cholylsarcosine during ursodeoxycholic acid treatment of primary biliary
cirrhosis.
AB - We postulated that coadministration of cholylsarcosine with ursodeoxycholic acid
might provide additional benefit to primary biliary cirrhosis patients with an
incomplete response to ursodeoxycholic acid. Our aim was to test the tolerability
and the effect of adjuvant cholylsarcosine on liver tests and plasma cholesterol
in primary biliary cirrhosis patients receiving ursodeoxycholic acid. Four
primary biliary cirrhosis patients, who, despite more than a year of
ursodeoxycholic acid therapy, had one or more liver tests persistently equal to
or greater than twice the upper limit of normal, received cholylsarcosine (12-15
mg/kg/day) in addition to ursodeoxycholic acid (13-15 mg/kg/day) for six weeks in
an open label study. Values of liver tests and plasma cholesterol, determined
every two weeks, remained unchanged. One patient discontinued cholylsarcosine at
week 4 because of new-onset pruritus. Analysis of duodenal bile acids in one
patient showed 52% enrichment in cholylsarcosine and hydrophilic bile acids
constituted 87% of total bile acids. It is concluded that the addition of
cholylsarcosine to ursodeoxycholic acid did not influence liver tests in four
primary biliary cirrhosis patients who had not responded completely to
ursodeoxycholic acid alone. Cholylsarcosine was absorbed and became a dominant
biliary bile acid; its administration was associated with increased pruritus.
PMID- 9635621
TI - Esophageal varices in rat models of liver cirrhosis.
AB - Animal models resembling the human situation are very useful to investigate human
disease. However, there has been no evidence of esophageal varices in rats with
liver cirrhosis. In the present study, to determine whether intrahepatic portal
hypertension produced by liver cirrhosis induces esophageal varices in rats, the
esophagus was examined endoscopically in rat models of liver cirrhosis. All rats
given carbon tetrachloride or thioacetamide and six of seven rats given a choline
deficient diet had esophageal varices or venous dilatation after 16 weeks of
treatment, although the varices in one rat given carbon tetrachloride and in two
rats given a choline-deficient diet were reduced from weeks 16 to 18. These
findings suggest that timing is important when studying esophageal varices in rat
models of liver cirrhosis. It is concluded that certain models of liver cirrhosis
in rats could be used as models of esophageal varices due to intrahepatic portal
hypertension.
PMID- 9635622
TI - Effects on gastric circulation of treatment for portal hypertension in cirrhosis.
AB - We evaluated the gastric circulatory effects of the type of treatment
administered for portal hypertension. Of 14 patients with cirrhosis, seven
received a transjugular intrahepatic portosystemic shunt (TIPS; group T) and
seven received percutaneous transhepatic portographic embolization (PTPE; group
P). Patients were evaluated over the course of one year. After treatment, portal
venous pressure was significantly reduced from 39 +/- 6 cm H2O to 32 +/- 5 (P <
0.001) in group T and was significantly elevated from 29 +/- 10 to 33 +/- 8 (P <
0.05) in group P. The portal flow velocity (Vmean) was significantly higher in
group T vs group P (P < 0.0001). The congestion index was significantly lower in
group T than in group P (P < 0.0001). The gastric mucosal blood flow was
increased in group T but was unchanged in group P. Esophageal varices showed some
improvement in both groups, but the portal hypertensive gastropathy was improved
only in group T. These findings help to explain the differing effects on the
gastric circulation related to the type of treatment used for portal
hypertension.
PMID- 9635623
TI - Hepatitis G and C viruses respond to interferon-alpha with different virologic
kinetics.
AB - The aim of this work was to specify the time course of response to interferon
(IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected
individuals. A group of 33 patients, undergoing 12 months of IFN therapy for
chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to
select seven coinfected patients. Spontaneous recovery from HGV infection was
excluded through the detection of antibodies to the envelope-2 protein of HGV and
HCV isolates were genotyped. Within three months of treatment, we found that HGV
RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable
response was very low (1/7). In addition, considering the same individuals
separately, it was shown that HGV and HCV responded to IFN with different
kinetics in 5/7 patients. Taken together, these results underscore the importance
of the virological basis of the resistance to IFN treatment.
PMID- 9635624
TI - Prognostic evaluation of early indicators in fulminant hepatic failure by
multivariate analysis.
AB - Viral hepatitis is the commonest cause of fulminant hepatic failure (FHF) in
developing countries. We evaluated the early indicators of prognosis in these
patients by multivariate analysis. The records of 204 consecutive patients with
acute liver failure admitted with hepatic encephalopathy over five years were
studied. The etiology of these patients included virus related in 186 (91.1%),
drug induced in 15 (7.4%), Wilson's disease in one (0.5%), acute Budd-Chiari
syndrome in one (0.5%), and malignant infiltration in one (0.5%). Patients with
FHF complicating viral hepatitis were analyzed by univariate and multivariate
analysis. These patients were further subclassified depending upon the interval
between the onset of jaundice and the onset of encephalopathy into hyperacute
(HALF; interval 0-7 days), acute (ALF; interval 8-28 days) and subacute liver
failure (SALF; interval 4-12 weeks). Sixty (32.3%) patients with viral hepatitis
survived. Univariate analysis showed that the interval between onset of
encephalopathy and onset of jaundice, grade of encephalopathy, raised
intracranial pressure, prothrombin time, and serum bilirubin levels on admission
were related to outcome in these patients. Multivariate logistic regression
analysis showed that the presence of raised intracranial pressure at the time of
admission, prothrombin time >100 sec on admission, age (>50 yr), and onset of
encephalopathy seven days after onset of jaundice were associated with poor
prognosis. Forty seven (37.0%) of 129 patients with HALF survived compared with 9
(22.5%) of 40 with ALF and 4 (21.1%) of 19 with SALF (P = NS). Raised
intracranial pressure was more frequent in patients with HALF (48.8%) than in
patients with ALF (32.5%) and SALF (15.8%; P = 0.01), while clinically detectable
ascites was more frequent in patients with SALF (78.9%) compared with HALF
(19.7%) and ALF (37.5%; P < 0.0001). The factors adversely affecting the outcome
in our patients with FHF complicating viral hepatitis include presence of overt
clinical features of raised ICP at the time of hospitalization, prothrombin time
(>100 sec) on admission, age (>50 yr), and onset of encephalopathy seven days
after onset of jaundice.
PMID- 9635625
TI - Prognostic value of generation of growth hormone-stimulated insulin-like growth
factor-I (IGF-I) and its binding protein-3 in patients with compensated and
decompensated liver cirrhosis.
AB - Our aim was to study the prognostic value of growth hormone (GH) -stimulated
insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3)
generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP)
score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7)
with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and
IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of
recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were
followed prospectively for three years. Six patients (40%) died during the follow
up period, of whom half had a CP score <9. Mean serum IGF-I levels 24 hr after
rhGH injection (group 1 vs group 2, 17.4 +/- 6.8 vs 7.4 +/- 0.7 nmol/liter)
predicted survival with 93% accuracy. Levels <10 nmol/liter portended a poor
prognosis, with 15% survival at one year, whereas levels >10 nmol/liter had a
100% survival rate at one and two years, respectively. Baseline IGF-I (9.98 +/-
2.0 vs 6.38 +/- 0.8 nmol/liter), GHBP (9.2 +/- 3 vs 5.7 +/- 0.8%/50 microl), and
IGFBP-3 serum levels at baseline (1.7 +/- 0.3 vs 0.86 +/- 0.2 mg/liter) and at 24
hr (2.04 +/- 0.38 vs 0.99 +/- 0.3 mg/liter) did not add to the predictive value
of stimulated IGF-I levels at 24 hr and were less accurate in predicting the
outcome in comparison to CP score (80%). We conclude that stimulated IGF-1 <10
nmol/liter may be a true predictor of a negative prognosis in patients with liver
cirrhosis.
PMID- 9635626
TI - Antibodies to Ro/La, Cenp-B, and snRNPs antigens in autoimmune hepatitis of North
America versus Asia: patterns of immunofluorescence, ELISA reactivities, and HLA
association.
AB - To assess whether demography is one of the important factors determining antibody
response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K,
B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH)
from North America and Asia, respectively, by immunofluorescent (IF) and
recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease
indices were analyzed. The frequency and titer of individual antibodies differed
significantly between the groups. Patients with speckled patterns were younger in
both regions and had higher aspartate aminotransferase levels only in North
America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61,
DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and
DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1,
B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and
DR4 in North America, and A2 in Asia, were associated with concurrent immunologic
disorder. Individual ANA clusters correlated with individual HLA in the
demography, and different HLA alleles might determine disease expression as well
as different ANA being produced in AIH.
PMID- 9635627
TI - Beer affects oxidative stress due to ethanol in rats.
AB - The relationship between chronic moderate beer consumption and oxidative stress
was studied in rats. Animals were fed three different isocaloric diets for six
weeks: a beer-containing diet (30% w/w), an ethanol-supplemented diet (1.1 g/100
g, the same as in the beer diet) and an alcohol-free basal diet. At the end of
the feeding period, rats were analyzed for plasma and liver oxidative status.
Some livers were isolated and exposed to ischemia-reperfusion to assess the
additional oxidative stress determined by reperfusion. No significant differences
in plasma antioxidant status were found among the three dietary groups.
Lipoproteins from the beer group, however, showed a greater propensity to resist
lipid peroxidation. Ischemia caused a decrease in liver energy and antioxidant
status in all groups. Nevertheless, ATP was lower in the livers of rats exposed
to the ethanol diet. During reperfusion, lipoperoxidation increased significantly
in all groups. However, livers obtained from ethanol-treated rats showed the
higher formation of lipoperoxides. In conclusion, a moderate consumption of beer
in a well-balanced diet did not appear to cause oxidative stress in rats;
moreover, probably through its minor components, beer could attenuate the
oxidative action of ethanol by itself.
PMID- 9635628
TI - Rapid diagnostic test for detection of Cys282Tyr mutation in hereditary
hemochromatosis.
PMID- 9635629
TI - Collagenous colitis and Yersinia enterocolitica infection.
AB - Collagenous colitis is a rare clinical and pathological entity characterized by
watery diarrhea and deposition of collagen beneath the surface epithelium of the
colon. Its etiology is unknown. We present a careful retrospective
clinicopathological analysis of six patients with collagenous colitis diagnosed
at our hospital during a three-year period. Three of the patients had had a
Yersinia enterocolitica infection, detected by stool culture and elevated serum
antibody titers, preceding the diagnosis of collagenous colitis. Four patients
had duodenal villous atrophy, which in two patients was refractory to a gluten
free diet. We propose that Yersinia enterocolitica infection may be a triggering
factor for the development of collagenous colitis in some cases. Duodenal villous
atrophy not responding to gluten withdrawal is common in association with
collagenous colitis.
PMID- 9635631
TI - Activated protein C resistance, thrombophilia, and inflammatory bowel disease.
AB - Thromboembolic events frequently complicate the clinical course of patients with
inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this
tendency. Resistance to activated protein C is the most recently described
thrombophilic state and may account for up to 40% of patients with thrombophilia.
Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82
years). Three patients had a history of thrombotic episodes. The 37 controls
included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease
activity was assessed using the Harvey Bradshaw index for patients with Crohn's
disease and the Truelove and Witts grading system for patients with ulcerative
colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S,
activated protein C resistance (APCR), and the presence of a lupus anticoagulant
(LA) were determined. Median ATIII levels in patients with IBD were significantly
lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2
vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in
7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P =
0.017). No significant difference was observed in levels of inherited
thrombophilic factors and in particular APCR between IBD patients and controls.
In conclusion, the presence of inherited thrombophilic defects, in particular
APCR, is uncommon in patients with IBD and does not merit routine screening.
PMID- 9635630
TI - Effect of leuprolide acetate in treatment of abdominal pain and nausea in
premenopausal women with functional bowel disease: a double-blind, placebo
controlled, randomized study.
AB - We have previously reported impressive results in using a gonadotropin-releasing
hormone analog, leuprolide acetate (Lupron), in the treatment of moderate to
severe symptoms (especially abdominal pain and nausea) in patients with
functional bowel disease (FBD). Pain is the hallmark of patients with FBD, and
there is no consistent therapy for the treatment of these patients. The purpose
of the present study was to expand the investigation to study similar patients
(menstruating females) in a multicenter, double-blind, placebo-controlled,
randomized study using Lupron Depot (which delivers a continuous dose of drug for
one month), 3.75 mg (N = 32) or 7.5 mg (N = 33), or placebo (N = 35) given
intramuscularly every four weeks for 16 weeks. Symptoms were assessed using daily
diary cards to record abdominal pain, nausea, vomiting, early satiety, anorexia,
bloating, and altered bowel habits. Additional assessment tools were quality of
life questionnaires, psychological profile, oral-to-cecal transit using the
hydrogen breath test, antroduodenal manometry, reproductive hormone levels, and
global evaluations by both patient and investigator. Patients in both Lupron
Depot-treated groups showed consistent improvement in symptoms; however, only the
Lupron Depot 7.5 mg group showed a significant improvement for abdominal pain and
nausea compared to placebo (P < 0.001). Patient quality of life assessments and
global evaluations completed by both patient and investigators were highly
significant compared to placebo (P < 0.001). All reproductive hormone levels
significantly decreased for both Lupron Depot-treated groups by week 4 and were
significantly different compared to placebo at week 16 (P < 0.001). This study
shows that leuprolide acetate is effective in controlling the debilitating
symptoms of abdominal pain and nausea in patients with FBD.
PMID- 9635632
TI - Ischemic colitis, pulmonary embolism, and right atrial thrombosis in a patient
with inherited resistance to activated protein C.
PMID- 9635633
TI - Procalcitonin--marker, or mediator?
PMID- 9635634
TI - Interpreting the venous-arterial PCO2 difference.
PMID- 9635635
TI - Adding fuel to the fire--the supranormal oxygen delivery trials controversy.
PMID- 9635636
TI - Outcome of septic shock: location, location, location.
PMID- 9635637
TI - Accentuate the positive, don't eliminate the negative.
PMID- 9635638
TI - Oxygen delivery: tusks versus flow.
PMID- 9635639
TI - Bedside placement of enteral feeding tubes in the intensive care unit.
PMID- 9635640
TI - Is there an answer to preventing unplanned extubations?
PMID- 9635641
TI - On hemoglobin, hemorrhage, hypotension, and ... nitric oxide.
PMID- 9635642
TI - Performance evaluations of mechanical ventilators: music to my ears.
PMID- 9635643
TI - Understanding the enigma of hepatic failure.
PMID- 9635644
TI - Mannitol: an old friend on the skids?
PMID- 9635645
TI - Can gastric intramucosal pH measurement be useful in pediatric critical illness?
PMID- 9635646
TI - Mortality is increased by procalcitonin and decreased by an antiserum reactive to
procalcitonin in experimental sepsis.
AB - OBJECTIVES: Procalcitonin (ProCT), the precursor to the calcitonin hormone, is
abnormally increased in experimental and clinical systemic inflammation,
including sepsis. Initially, we investigated the effects of supraphysiologic
amounts of ProCT administered to animals with septic peritonitis. Subsequently,
we evaluated the efficacy of prophylactic and therapeutic immune blockade of
ProCT in this lethal model of sepsis. DESIGN: Prospective, experimental,
controlled study. SETTING: Animal research laboratory approved by the American
Association for the Accreditation of Laboratory Animal Care at a Veterans Affairs
Medical Center. SUBJECTS: Young male Golden Syrian hamsters, weighing 90 to 120
g. INTERVENTIONS: In the first study, serum ProCT concentrations were measured in
animals at 0, 3, 6, 12, and 24 hrs after induction of sepsis by intraperitoneal
implantation of pellets containing Escherichia coli (5 x 10(8) colony-forming
units/pellet). In the second study, with mortality as the end point, 30 microg/kg
of isolated, purified human ProCT in 10% hamster serum (experimental) or an equal
volume of 10% hamster serum (control) were administered intravenously at the time
of the E. coli peritoneal implantation. In the third study, experimental animals
received intraperitoneal injections of a multiregion-specific goat antiserum
reactive to hamster ProCT 1 hr before and 24 hrs after E. coli implantation,
while control animals received nonimmune goat serum at the same time points. In
the final study, the same antiserum was administered in five divided doses during
the 24 hrs after the insertion of E. coli. MEASUREMENTS AND MAIN RESULTS: In the
initial study, ProCT concentrations were increased shortly after induction of
sepsis and peaked at 12 hrs. Administration of exogenous ProCT to septic animals
significantly increased mortality compared with control animals (93% vs. 43%,
p=.02). Prophylactic blockade of ProCT almost completely protected the animals
from the lethal effects of sepsis: the 102-hr mortality rate in the experimental
group was 6% compared with 62% in the control group (p < .003). In the
therapeutic trial, the 102-hr mortality rate was 54% in experimental animals
compared with 82% in control animals (p < .045). CONCLUSIONS: These results
demonstrate that increased ProCT exacerbates mortality in experimental sepsis,
whereas neutralization of ProCT increases survival. Thus, ProCT, in addition to
being an important marker of severity of systemic inflammation and mortality, is
an integral part of the inflammatory process and directly affects the outcome.
PMID- 9635647
TI - Value of the venous-arterial PCO2 gradient to reflect the oxygen supply to demand
in humans: effects of dobutamine.
AB - OBJECTIVE: To test the value of venous-arterial PCO2 gradient (deltaPCO2)
measurements to reflect the adequacy of cardiac index (CI) to oxygen demand in
patients submitted to rapid changes of CI and oxygen demand. DESIGN: Prospective,
comparative study. SETTING: Medical intensive care unit of a university hospital.
PATIENTS: Ten patients with congestive heart failure exhibiting low baseline CI
(< or =2.5 L/min/m2) but no evidence of global tissue hypoxia, as attested by the
absence of clinical signs of shock and by normal blood lactate concentrations.
INTERVENTIONS: Infusion of incremental doses of dobutamine: 0 (D0), 5 (D5), 10
(D10), and 15 (D15) microg/kg/min. MEASUREMENTS AND MAIN RESULTS: The CI
increased by a linear fashion from D0 (1.6+/-0.1 L/min/m2) to D15 (2.4+/-0.2
L/min/m2) (p< .05). The mixed venous oxygen saturation (SVO2) increased from D0
(49+/-2%) to D10 (61+/-2%) (p < .05) and remained unchanged from D10 to D15 (60+/
2%). The oxygen extraction ratio (O2 ER) and the deltaPCO2 decreased from D0
(48+/-2% and 9+/-1 torr [1.2+/-0.3 kPa], respectively) to D10 (36+/-2% and 5+/-1
torr [0.7+/-0.1 kPa], respectively) (p < .05 for both comparisons) and remained
unchanged from D10 to D15 (36+/-2% and 6+/-1 torr [0.8+/-0.1 kPa], respectively).
The biphasic courses of SVO2, O2 ER, and deltaPCO2 were related to the course of
oxygen consumption that remained constant from D0 (113+/-9 mL/min/m2) to D10
(112+/-8 mL/min/m2) and significantly increased from D10 to D15 (127+/-10
mL/min/m2) (p <.05). CONCLUSIONS: deltaPCO2 can be reliably used at the bedside
for informing on the adequacy of CI with respect to a given metabolic condition,
and particularly for detecting changes in oxygen demand (e.g., the changes
accompanying drug-induced changes in CI). In this regard, deltaPCO2, together
with O2 ER and SVO2, can help to assess the adequacy of CI to global oxygen
demand.
PMID- 9635648
TI - Relationship of mortality to increasing oxygen delivery in patients > or = 50
years of age: a prospective, randomized trial.
AB - OBJECTIVE: To investigate the relationship of mortality to early resuscitation
using two levels of oxygen delivery (DO2) in critically ill surgical patients >
or =50 yrs of age who were stratified into groups: age < or =75 yrs (age 50 to 75
yrs group); and age >75 yrs (age >75 yrs group). DESIGN: A prospective,
randomized trial, continued from a previous project. SETTING: Surgical intensive
care unit, university affiliated. PATIENTS: Consecutive patients, >50 yrs of age,
unable to generate a DO2 of > or =600 mL/min/m2 with fluid resuscitation alone,
with a diagnosis of systemic inflammatory response syndrome, sepsis, severe
sepsis, septic shock, and/or acute respiratory distress syndrome. INTERVENTIONS:
During the first 24 hrs of resuscitation, patients were randomized to receive
fluids, blood transfusions, and vasoactive agents in order to achieve DO2
treatment goals of > or =600 mL/ min/m2 in the protocol group and 450 to 550
mL/min/m2 in the control group. MEASUREMENTS AND MAIN RESULTS: One hundred five
patients completed the study. In patients aged 50 to 75 yrs, the mortality rate
was 21% (9/43) in the protocol group and 52% (12/23) in the control group (p=.01,
95% confidence interval of -58% to -4%). In patients >75 yrs of age, the
mortality rate was 57% (12/21) in the protocol group and 61% (11/18) in the
control group. Oxygen extraction ratios (O2ER) and oxygen consumption values were
significantly (p=.02) lower in the age >75 yrs group compared with the age 50 to
75 yrs group. CONCLUSIONS: Patients 50 to 75 yrs of age receiving a DO2 of > or
=600 mL/min/m2 demonstrated a statistically significant (p=.01) improved survival
rate over patients in the control group. Patients >75 yrs of age demonstrated no
benefit from attempts to increase DO2 to >600 mL/min/m2, and they may have been
overtreated as reflected by the lower O2ER values in this age group. Treating to
an O2ER that reflects a balance between oxygen consumption and DO2 may be an
alternative goal that allows individual titration.
PMID- 9635649
TI - Septic shock: an analysis of outcomes for patients with onset on hospital wards
versus intensive care units.
AB - OBJECTIVE: To determine if early interventions for septic shock were associated
with reduced mortality. DESIGN: Retrospective cohort study. SETTING: University
hospital intensive care unit (ICU) and general wards. PATIENTS: Forty-one
consecutive patients prospectively identified with positive blood cultures and
septic shock. Although all patients were eventually treated in an ICU, ten (24%)
patients were on a general ward at the onset of septic shock, and 31 (76%) were
in an ICU setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over a
period of 9 mos, a cohort of 41 patients who had positive blood cultures and
septic shock was prospectively identified. The 28-day crude mortality was 46% (19
deaths). We compared the management of septic shock and outcome for patients on a
general ward vs. those patients in an ICU setting. Of the ten patients on the
ward at time of shock onset (median age 55.5 yrs; median Acute Physiology and
Chronic Health Evaluation [APACHE] II score of 18.5), seven (70%) died. In
contrast, the 31 patients receiving intensive care when shock developed were
older and more ill (median age 66 yrs; median APACHE II 24), yet had a mortality
of 39% (12 deaths). The odds ratio (OR) for death for ward patients compared with
ICU patients was 3.57 (p=.17). In a multivariate logistic regression analysis,
two risk factors for mortality were important: APACHE II score (p=.015) and ward
status (p=.08). Candida species in the bloodstream is known to have a high
attributable mortality. When type of bloodstream pathogen (Candida species vs.
bacteria) was added to the model, APACHE II (OR 2.64 for 10-unit increase)
remained significant (p=.014), but ward status (OR 3.97) became statistically
nonsignificant (p=.222). The patients who were on a general ward when their shock
developed had a median delay of 67 mins before transfer to an ICU setting. Ward
patients received an intravenous fluid bolus after a median delay of 27 mins,
whereas those in the ICU who received a fluid bolus did so after a median of 15
mins (p=.48). Ward patients also had a median delay of 310 mins to receive
inotropic support compared with a median 22.5 mins (p=.037) for the patients in
an ICU setting when shock started. CONCLUSIONS: The data suggest that for
patients with septic shock on wards, there were clinically important delays in
transfer of patients to the ICU, receipt of intravenous fluid boluses, and
receipt of inotropic agents. However, the most powerful predictors of mortality
were APACHE II scores and bloodstream infection with Candida species.
PMID- 9635650
TI - Effects of continuous negative extrathoracic pressure versus positive end
expiratory pressure in acute lung injury patients.
AB - OBJECTIVE: To compare the effects of continuous negative extrathoracic pressure
(CNEP) and positive end-expiratory pressure (PEEP) at the same level of
transpulmonary pressure. DESIGN: Prospective analysis. SETTING: Medical intensive
care unit of a university hospital. PATIENTS: Nine consecutive acute lung injury
patients. Patients with cardiac failure and patients with chronic lung disease
were excluded from the investigation. INTERVENTIONS: The patients were sedated
and paralyzed while receiving mechanical ventilation and were studied in three
different conditions: a) using a PEEP of 0 cm H2O (zero end-expiratory pressure);
b) using a PEEP of 15 cm H2O; c) using CNEP. CNEP was applied to the thorax and
the upper abdomen and its level was chosen to obtain a transpulmonary pressure
similar to the one observed at a PEEP of 15 cm H2O. All patients had an arterial
catheter, a pulmonary artery catheter, and a thermistor-tip fiberoptic catheter
for thermo-dye-dilution in the femoral artery. These catheters were connected to
an integrated monitoring system. We also placed an esophageal catheter in each
patient to detect esophageal pressure. MEASUREMENTS AND MAIN RESULTS: For each
step, we assessed the hemodynamic variations by measuring intravascular pressures
(via a pulmonary artery catheter), transmural pressures (computed by subtracting
esophageal pressure from intravascular pressure), and blood volumes (derived from
the technique of double indicator). The application of CNEP of -20+/-0.7 cm H2O
produced a venous admixture and PaO2/FO2 improvement similar to that obtained
with a PEEP of 15 cm H2O. This procedure is associated with a higher cardiac
index (5.5+/-1.5 vs. 4.6+/-1.2 L/min/m2; p < .05) coupled with lower central
venous pressure, pulmonary artery occlusion pressure, and higher transmural
pressures and blood volume parameters. CONCLUSIONS: In acute lung injury
patients, a CNEP of -20 cm H2O has the capability to obtain transpulmonary
pressure and lung function improvement similar to a PEEP of 15 cm H2O. CNEP
differs from the positive pressure by increasing the venous return and the
preload of the heart, and has no negative effects on cardiac performance.
PMID- 9635651
TI - Delivery of high concentrations of inspired oxygen via Tusk mask.
AB - OBJECTIVES: Nonrebreather face masks (NRM) are frequently used in patients with
respiratory distress and profound hypoxemia. A simpler modification to the
partial rebreather face mask, using only two pieces of respiratory tubing or
"tusks," has also been shown to increase FiO2 compared with the NRM in five
normal subjects. Clinically, we have observed this modification to further
increase PaO2 in critically ill patients already using the NRM in the intensive
care unit. This study was designed to compare the Tusk mask with the NRM in both
a larger group of normal subjects and in patients with underlying lung disease.
DESIGN: Prospective, randomized, crossover study. SETTING: A university teaching
hospital and tertiary care referral center. SUBJECTS: Sixteen normal subjects (11
male and 5 female; age 30.4+/-6.8 [SD] yrs) and seven patients with interstitial
lung disease (ILD) (3 male and 4 female; age 68.1+/-11.9 yrs). INTERVENTIONS:
Subjects and patients served as their own controls and were randomized to wear
either the NRM or Tusk mask for a 30-min period. After a 60-min washout period,
the other mask was applied. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas
measurements were performed immediately before and at the end of each 30-min test
period. Respiratory synchronization during the study period was achieved, using a
metronome. In the normal subjects, PaO2 using the NRM and Tusk masks increased
290.0+/-57.1 torr (38.6+/-7.6 kPa) and 330.0+/-68.9 torr (44.0 +/-9.2 kPa),
respectively (p=.032). PaO2 increased 293.4+/-38.0 torr (39.1+/-5.1 kPa) with the
NRM and 378.4+/-61.7 torr (50.4+/-8.2 kPa) with the tusk mask (p=.001) in the
patients with ILD. There was no statistically significant change seen in mean
PaCO2 with either mask in either group. The mean PaO2 returned to within 6% of
baseline in both groups after the washout period. CONCLUSIONS: Both normal
subjects and patients with compromised pulmonary function achieved a higher PaO2
using a Tusk mask than when using the conventional NRM, at the same oxygen flow
rate. Patients with hypoxemia may obtain lifesaving benefit from the additional
concentration of oxygen delivered via the Tusk mask.
PMID- 9635652
TI - Air insufflation technique of enteral tube insertion: a randomized, controlled
trial.
AB - OBJECTIVE: To test air insufflation as an adjunct to placement of enteral feeding
tubes. DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a
tertiary hospital. SUBJECTS: Sixty-four consecutive patients requiring enteral
nutrition, in whom a decision to insert a nasoenteral feeding tube was made.
INTERVENTIONS: A 12-Fr feeding tube was inserted to the level of the fundus of
the stomach. A 60-mL syringe was used to pump 500 mL of air into the stomach. The
tube was then advanced. An abdominal flat plate was obtained within 2 hrs of
completion of the procedure and the tube position noted. If the tube was not in
the duodenum, the patient was placed on a promotility agent and a repeat
radiograph was performed the next day. The technique varied from our control
technique only by the instillation of air. MEASUREMENTS AND MAIN RESULTS: Using
the study technique, 21 of 32 tubes were successfully placed, as seen on the
initial radiograph, in our study patients compared with only 12 of 34 tubes in
our control patients (p< .02). In addition, the success rate at 24 hrs was 25 of
32 vs. 16 of 34 (p< .02). Only 3 of 21 tubes placed in the antrum, body, or
fundus of the stomach advanced to the duodenum the following day, compared with 5
of 12 tubes initially placed in the pylorus (p< .075). No complications were
noted. CONCLUSION: Instilling air into the stomach may facilitate the ability to
get the feeding tube to the level of the pylorus, at which point it is more
likely to advance into the duodenum and beyond.
PMID- 9635653
TI - White blood cell counts and plasma C3a have synergistic predictive value in
patients at risk for acute respiratory distress syndrome.
AB - OBJECTIVE: To investigate and select nonassociated variables with predictive
value for acute respiratory distress syndrome (ARDS) in patients at risk. DESIGN:
Prospective, observational study. SETTING: A university hospital intensive care
unit. PATIENTS: Twenty-four critically ill patients with different risk factors
for ARDS. INTERVENTIONS: Arterial and mixed venous blood, as well as urine
samples, were collected. Invasive hemodynamic measurements were performed.
MEASUREMENTS AND MAIN RESULTS: Fifty-nine variables pertaining to the
cardiorespiratory, hepatic, immunologic, and renal systems and including plasma
complement activation products C3a and SC5b-9 and polymorphonuclear elastase,
were determined every 6 hrs for 3 days in patients at risk for ARDS. Associations
among variables were investigated and the predictive value of nonassociated
variables for ARDS was determined. Patients who developed ARDS (n=8) had lower
white blood cell counts at the time they entered the study (p=.006) and during
the first 24 hrs thereafter (p=.032). Also, plasma C3a concentrations were
markedly higher during the first 24 hrs in patients who developed ARDS (p=.006).
Plasma C3a had better predictive value than did white blood cell counts for
cutoff points set by discriminant analysis at 1075 ng/mL (1.075 x 10(-3) g/L) and
5700 cells/mL, respectively. The combination of both variables in a discriminant
function improved the predictive value for ARDS. CONCLUSIONS: The most notable
and nonassociated alterations observed in patients who developed ARDS were lower
white blood cell counts and higher plasma C3a concentrations compared with counts
and concentrations in patients who did not develop ARDS. Plasma C3a
concentrations showed better predictive value than white blood cell counts. The
combination of white blood cell counts with plasma C3a concentrations
synergistically improved the predictive value for ARDS. This combination may
prove useful for identifying subpopulations at highest risk for ARDS and may
contribute to make treatment at an early stage of the syndrome possible.
PMID- 9635654
TI - Unplanned extubation: risk factors of development and predictive criteria for
reintubation.
AB - OBJECTIVES: To define patients at risk for unplanned extubation; to assess the
influence of nursing workload on the incidence of unplanned extubation; and to
determine predictive criteria for patients requiring reintubation. DESIGN: A
prospective, case-control study, with 10 and 15 mos of data collection. SETTING:
University medical intensive care department. PATIENTS: In the first study, which
lasted 10 mos, unplanned extubation occurred in 40 (14%) of 281 ventilated and
intubated patients; 36 cases were sufficiently documented to be compared with 74
intubated and ventilated controls. In the second study, which lasted 15 mos, the
reintubated patients (n=23) of a series of 62 unplanned extubation patients were
compared with those who were not reintubated (n=39). INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: The following parameters were recorded: gender,
age, main reason for admission, Simplified Acute Physiology Score II, route of
intubation (oral or nasotracheal), tube diameter, ventilatory mode, FiO2,
frequency and tidal volume delivered by the ventilator immediately before
unplanned extubation, arterial blood gases performed 24 hrs before unplanned
extubation, the presence of any sedation with, in this case, the last Ramsay
score, the presence of hand restraints, the presence of weaning of ventilation,
the accidental or deliberate nature of unplanned extubation, the Glasgow Coma
Score at the time of unplanned extubation, the duration of ventilation before
unplanned extubation, total duration of ventilation and stay in the intensive
care unit, and the patient's survival or death. The nursing workload was
evaluated using a score derived from the Projet de Recherche en Nursing and
adapted to intensive care. Unplanned extubation patients were more frequently
intubated orally than controls (33.3% vs. 14.9%, respectively; p< .05). In the
population of sedated patients, unplanned extubation patients were more
frequently agitated than controls (60% vs. 19%, respectively; p < .05). The
nursing workload did not differ between days with and days without unplanned
extubation. Twenty-three (37%) of the 62 cases of documented unplanned extubation
were reintubated. Predictive factors of reintubation are, in decreasing order of
importance: Glasgow Coma Score of <11, accidental nature of unplanned extubation,
and a PaO2/FiO2 ratio <200 torr (<26.7 kPa). CONCLUSIONS: Patients at risk for
unplanned extubation are characterized by oral intubation and insufficient
sedation. In the department studied, and with the specific score used, we did not
observe a relationship between the nursing workload and the incidence of
unplanned extubation. A Glasgow Coma Score of <11, the accidental nature of
unplanned extubation, and a PaO2/FiO2 ratio <200 torr (<26.7 kPa) are factors
associated with a risk of reintubation.
PMID- 9635655
TI - A rapid assay for the detection of circulating D-dimer is associated with
clinical outcomes among critically ill patients.
AB - OBJECTIVE: To determine whether the results of a rapid, semiquantitative assay
for the detection of circulating D-dimer in whole blood (SRDD assay) are
associated with the occurrence of clinical outcomes among critically ill
patients. DESIGN: Prospective, blinded, single-center study. SETTING: Medical
intensive care unit (ICU) of Barnes-Jewish Hospital, St. Louis, MO, a university
affiliated teaching hospital. PATIENTS: Three hundred twenty-three adult patients
admitted to a medical ICU. INTERVENTIONS: Collection of blood samples within 24
hrs of ICU admission. MEASUREMENTS AND MAIN RESULTS: The main outcome measures
evaluated included vascular thrombosis, hospital mortality, and the development
of multiorgan dysfunction. Fifty (15.5%) patients were found to have increased
concentrations of D-dimer as detected by the SRDD assay within 24 hrs of ICU
admission. The concentrations of plasma D-dimer simultaneously measured by an
enzyme immunoassay based on the same antibody were significantly greater among
patients with a positive SRDD assay compared with patients with a negative SRDD
assay (1214+/-483 vs. 405+/-407 ng/mL; p< .001). The hospital mortality rate was
significantly greater among SRDD-positive patients compared with SRDD-negative
patients (32.0% vs. 15.0%; p=.004). SRDD-positive patients also had significantly
greater frequencies of acquired multiorgan dysfunction (48.0% vs. 17.6%; p <
.001), severe sepsis or septic shock (56.0% vs. 20.9%; p< .001), and vascular
thrombosis (14.0% vs. 4.0%; p=.005) compared with SRDD-negative patients.
Multiple logistic regression analysis identified the presence of increased
concentrations of D-dimer, detected by a positive SRDD assay, as being
independently associated with vascular thrombosis (adjusted odds ratio 5.06; 95%
confidence interval 2.96 to 8.65; p=.003) and the development of multiorgan
dysfunction (adjusted odds ratio 1.51; 95% confidence interval 1.28 to 1.78;
p=.012). CONCLUSIONS: Our preliminary investigation suggests that the results
from a rapid whole blood assay for the semiquantitative detection of circulating
D-dimer are associated with clinical outcomes among patients admitted to a
medical ICU. In addition, the use of D-dimer to identify the presence of active
intravascular thrombosis may identify patients likely to benefit from
antithrombotic therapies in the ICU setting.
PMID- 9635656
TI - Clinical death and the measurement of stressed vascular volume.
AB - OBJECTIVES: To measure stressed vascular volume in humans and to review the
concepts of stressed and unstressed vascular volume. DESIGN: Observational study
during surgical procedure. SETTING: Operating room at a university hospital.
PATIENTS: Five patients undergoing hypothermic circulatory arrest for surgery on
major vessels. INTERVENTION: We measured the volume that drained from the patient
to the reservoir of the pump when the pump was turned off. MEASUREMENTS AND MAIN
RESULTS: Stressed volume was 20.2+/-1.0 mL/kg, which is 30% of the predicted
blood volume of these patients. CONCLUSION: The amount of blood volume that
determines vascular filling pressure is only about a quarter of the total
predicted volume, which means that there is a large reserve of unstressed volume
that can be recruited to maintain vascular filling pressure.
PMID- 9635657
TI - Bedside determination of fluid accumulation after cardiac surgery using segmental
bioelectrical impedance.
AB - OBJECTIVES: Bioelectrical impedance analysis (BIA) is based on the physical
property of tissues to conduct electrical currents, impedance being inversely
related to tissue fluid content. At high frequency, the electrical current flows
across both intracellular and extracellular pathways, making the assessment of
fat-free mass possible while a low-frequency current flows through the
extracellular space. Similarly, segmental BIA may be used to assess segmental
body fluid repartition. The aim of this study was to assess fluid accumulation
after cardiac surgery by multiple frequency segmental BIA. DESIGN: Observational,
clinical study. SETTING: A 17-bed, surgical intensive care unit in a university
hospital. PATIENTS: Twenty-six patients before and after open-heart surgery with
cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After
surgery, fluid accumulation resulted in a decrease in whole-body and segmental
bioelectrical impedance in the arm and in the trunk. There was a good correlation
between the fluid accumulation measured by fluid balance and by whole-body or
segmental impedance changes. The major part (71%) of fluid accumulation occurred
in the trunk. Multiple frequency measurements did not indicate a fluid shift
between the intra- and extracellular compartments. CONCLUSION: Cardiac surgery
produced a significant decrease in segmental trunk BIA, reflecting fluid
accumulation at the trunk level.
PMID- 9635658
TI - Resuscitation after hemorrhage using recombinant human hemoglobin (rHb1.1) in
rats: effects on nitric oxide and prostanoid systems.
AB - OBJECTIVES: Hemoglobin-based oxygen carriers are designed to replace blood volume
and to increase oxygen delivery to tissues after blood loss. The goals of the
present study were two-fold: a) to determine the systemic and regional vascular
effects of resuscitation with recombinant human hemoglobin (rHb1.1) in rats
during controlled hemorrhage; and b) to determine whether nitric oxide (NO) or
prostaglandins were involved in the observed responses. DESIGN: Paralyzed,
ventilated rats were hemorrhaged (18 mL blood/kg body weight) during halothane
anesthesia and allowed to stabilize for 30 mins. Systemic and regional
hemodynamics and oxygen delivery were monitored at three time points, using the
radioactive microsphere method. Microspheres were first infused at the end of the
hemorrhage stabilization period (t=0 min). rHb1.1 (1 g/kg body weight) or rHb1.1
diluent (phosphate buffered saline, 36 mL/kg body weight) were infused over 20
mins and microspheres were administered again, 30 mins later (t=50 mins). Saline
(0.5 mL), indomethacin (5 mg/kg to inhibit cyclooxygenase), or NG-monomethyl-L
arginine (L-NMMA, 100 mg/kg, to inhibit NO synthase) were then infused in rHb1.1
treated rats and microspheres injected once more (t=80 mins). SETTING: Research
laboratory. SUBJECTS: Male Wistar rats (n=37). INTERVENTIONS: Recombinant human
hemoglobin (rHb1.1), rHb1.1 diluent (phosphate buffered saline) resuscitation of
hemorrhaged rats. Saline, L-NMMA, or indomethacin treatment after resuscitation.
MEASUREMENTS AND MAIN RESULTS: Resuscitation with rHb1.1 increased mean arterial
pressure (MAP), cardiac output, and systemic oxygen delivery significantly when
compared with diluent. After rHb1.1 resuscitation, regional blood flows were
significantly increased in skin, kidney, spleen, and heart compared with diluent
resuscitation. Compared with saline treatment after rHb1.1 resuscitation, L-NMMA
increased MAP and regional resistances in virtually all tissues; indomethacin did
not alter MAP, but increased resistance in the brain. CONCLUSIONS: These data
indicate that rHb1.1 resuscitation was more effective than diluent in improving
systemic and regional hemodynamics and oxygen delivery, suggesting that rHb1.1
may be of benefit in the treatment of acute blood loss. Increased resistance
after L-NMMA in the presence of rHb1.1 indicated that rHb1.1 resuscitation did
not eliminate NO dependent circulatory control. Increased resistance after
indomethacin in brain indicated that vasodilator prostanoids were important in
regulating vascular resistance in these tissues after rHb1.1 resuscitation.
PMID- 9635659
TI - Mechanical performance of clinically available, neonatal, high-frequency,
oscillatory-type ventilators.
AB - OBJECTIVE: To perform a functional evaluation of five different high-frequency,
oscillatory-type ventilators that are currently being marketed for neonatal high
frequency oscillation. DESIGN: Observational animal study. SETTING: Laboratory.
SUBJECTS: New Zealand White male rabbits. INTERVENTIONS: Oscillator waveforms and
delivered volumes were measured plethysmographically for the following
ventilators: the SensorMedics 3100 A; the Drager Baby Log 8000; the Metran
Humming V; the Infant Star; and the Infant Star 950. The independent variables
which were adjusted included frequency (5 to 15 Hz), amplitude (25% to 100%),
mean airway pressure (5 to 25 cm H2O) and lung injury. MEASUREMENTS AND MAIN
RESULTS: At 15 Hz, the volume delivered at the 100% amplitude setting varied from
2.1 to 8.8 mL. Generally, the delivered volume decreased with increasing
frequency, and with increased percentage of amplitude. Volume delivery was
relatively unaffected by mean airway pressure but decreased with lung injury.
Waveforms ranged from pure sinusoidal to a complex square wave. The handling of
inspiration/expiration time ratios was ventilator specific. The SensorMedics
inspiration/ expiration ratio is user selected over a range from 1:2.3 (30%
inspiratory time) to 1:1 (50% inspiratory time) and once selected it is
consistent over its entire range of operating frequencies. The Drager ratio is
machine determined and varied from 1:2.5 at 5 Hz to 1:1 at 15 Hz. Inspiratory
time of the Infant Star is machine set at 18 msecs such that the
inspiration/expiration ratio is 1:10.1 at 5 Hz and 1:2.7 at 15 Hz. The Humming V
has a fixed inspiration/expiration ratio of 1:1. The relationship of the mean
airway pressure displayed on the ventilator to the alveolar occlusion pressure
varied considerably among devices. The displayed mean pressure could either
overestimate (SensorMedics at 33% inspiratory time or Infant Star), approximate
(Humming V), or underestimate (Drager) the mean lung distending pressure measured
during a brief occlusion maneuver. CONCLUSIONS: The findings demonstrate large
variations in machine performance. The ventilators also differed profoundly in
complexity of operation and versatility as neonatal ventilators.
PMID- 9635660
TI - Hypoxia-reoxygenation is as damaging as ischemia-reperfusion in the rat liver.
AB - OBJECTIVE: We hypothesized that the extent of injury and release of xanthine
oxidase, an oxidant generator, into the circulation would be less in normal-flow
hypoxia-reoxygenation than in equal duration no-flow ischemia-reperfusion.
DESIGN: Randomized study. SETTING: University-based animal research facility.
SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The livers were isolated,
perfused, and then randomly subjected to 2 hrs of hypoxia (normal flow, low
oxygen) or ischemia (no flow, no oxygen), and 2 hrs of reperfusion. Hepatocytes
were also isolated, and were subjected to either: a) hypoxia (0, 2, 4, and 6
hrs); or b) hypoxia (2 and 4 hrs) with reoxygenation (2 hrs). MEASUREMENTS AND
MAIN RESULTS: The extent of liver injury (as assessed by release of
hepatocellular enzymes) and the release of xanthine oxidase were measured from
isolated-perfused rat livers and cultured hepatocytes. The pattern of release of
xanthine oxidase in isolated-perfused liver effluent was different in hypoxia
reoxygenation compared with ischemia-reperfusion. During hypoxia, xanthine
oxidase gradually increased in the effluent; then, the xanthine oxidase decreased
to low concentrations during reoxygenation. After ischemia, there was a sharp
spike in xanthine oxidase at 1 min of reperfusion, with a rapid decrease to low
concentrations. The total release of xanthine oxidase during hypoxia
reoxygenation was similar to that during ischemia-reperfusion. Lactate
dehydrogenase and other markers of liver injury showed a pattern of release that
was similar to that of xanthine oxidase, but the total release of markers was not
different between the two groups. In hepatocytes, most of the release of enzymes
occurred in hypoxia, and the rate of release was not different between hypoxia
and hypoxia-reoxygenation. CONCLUSIONS: Hypoxia-reoxygenation results in as much
damage to the liver as ischemia-reperfusion, and results in the release of a
similar amount of oxidant-producing xanthine oxidase into the circulation.
PMID- 9635661
TI - Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin
removal device--an alternative to protamine.
AB - OBJECTIVES: To evaluate the therapeutic efficacy and applicability of a heparin
removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity
adsorption as an alternative to protamine in reversing systemic heparinization
following cardiopulmonary bypass (CPB). DESIGN: A prospective study. SETTING:
University research laboratory. SUBJECTS: Adult female swine (n=7).
INTERVENTIONS: Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected
to 60 mins of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After
weaning from CPB, the right atrium was recannulated with a two-stage, dual-lumen
cannula which was connected to an HRD via extracorporeal circulation. Blood flow
was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the
plasma separation chamber of the HRD (where heparin was bound to PLL), and
reinfused into the right atrium. The HRD run time was determined by a previously
established mathematical model of first-order exponential depletion. MEASUREMENTS
AND MAIN RESULTS: Heart rate, mean arterial pressure, pulmonary arterial
pressure, central venous pressure, kaolin and celite activated clotting time
(ACT), activated partial thromboplastin time (APTT), heparin concentration, and
plasma free hemoglobin were obtained before, during, and after the use of the
HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT
was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove
90% total body heparin. Use of the HRD was not associated with any adverse
hemodynamic reactions or increases in plasma free hemoglobin. The heparin
concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000
secs and APTT >150 secs in all animals. During heparin removal, total body
heparin content followed first-order exponential depletion kinetics. At the end
of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with
kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and
APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables).
CONCLUSIONS: The HRD is capable of reversal of anticoagulation following CPB
without significant blood cell damage or changes in hemodynamics. The HRD,
therefore, can serve as an alternative to achieve heparin clearance in clinical
situations where use of protamine may be contraindicated.
PMID- 9635662
TI - Efficacy of inhaled prostanoids in experimental pulmonary hypertension.
AB - OBJECTIVES: To evaluate the effects of inhaled prostacyclin (PGI2) and inhaled as
well as intravenous prostaglandin E1 (PGE1) on thromboxane A2 mimetic-induced
pulmonary vasoconstriction. Active pulmonary vasoconstriction was to be
distinguished from passive resistance to blood flow. DESIGN: Prospective,
randomized, crossover study. SETTING: Experimental animal laboratory. SUBJECTS:
Eight anesthetized and paralyzed sheep. INTERVENTIONS: The stable thromboxane A2
mimetic, U46619, was infused in increasing dosage to obtain a stable pulmonary
hypertension of approximately 30 mm Hg. Subsequently, PGE1 aerosol (0.6, 6, 58,
259 ng/kg/min), intravenous PGE, (0.5 microg/kg/min), or PGI2 aerosol (27
ng/kg/min) were administered in randomized order. MEASUREMENTS AND MAIN RESULTS:
Active pulmonary vasoconstriction was assessed by determining the pulmonary
pressure-flow relationship (PPFR). For measurement of pulmonary artery flow, an
ultrasound flow probe was placed around the pulmonary artery after a sternotomy.
Pulmonary arterial pressure was measured with a pulmonary artery flotation
catheter. Flow was varied by partial occlusion of the inferior vena cava or
incremental opening of an arterio-venous fistula between the large neck vessels.
The primary end points were the slope of the resulting linear pressure-flow
relationship, and pulmonary vascular resistance (PVR). Infusion of U46619
increased the slope of the PPFR (2.9+/-0.7 vs. 4.2+/-1.2 mm Hg/L/min [median+/
semi-interquartile range]; p < or = .05), and PVR (221+/-20 vs. 424+/-57 dyne x
sec/cm5) (p < .05). Neither dose of PGE1 aerosol induced changes of the slope of
PPFR or PVR. In contrast, intravenous administration of the same drug reduced the
slope of the PPFR (4.0+/-1.0 vs. 3.1+/-0.4) (p < .05) but left PVR unchanged.
Inhalation of PGI2 reduced both the slope of the PPFR, slightly but
significantly, and PVR (424+/-98 vs. 323+/-26 dyne x sec/cm5) (p < .05).
CONCLUSIONS: This study is the first to show reduction of active pulmonary
vasoconstriction by PGI2 aerosol. Neither inhalation nor intravenous
administration of PGE1 reduced PVR but the latter reduced the slope of PPFR. We
conclude that PGE1 has potential for pulmonary vasodilation, but that it is
ineffective as an aerosol, even in high doses, in sheep. PVR may fail to reflect
drug-induced pulmonary vasodilation.
PMID- 9635663
TI - Gut intramucosal pH as an early indicator of effectiveness of therapy for
hemorrhagic shock.
AB - OBJECTIVE: To determine the value of intramucosal pH for evaluating the
effectiveness of treatment for hemorrhagic shock. DESIGN: Randomized, controlled
trial. SETTING: University center, animal laboratory. SUBJECTS: Eighteen piglets,
weighing 17 to 23 kg. INTERVENTIONS: Anesthetized animals were bled to a mean
arterial pressure (MAP) of 40 to 50 mm Hg and a 70% reduction in cardiac output
during a 1-hr period. This state was maintained for the next hour. The piglets
were treated with crystalloid solution to restore cardiac output and MAP during
the subsequent 80 mins of the experiment. Some animals were given vasoactive
drugs during volume therapy to modulate splanchnic perfusion and increase the
diversity of values of various variables. MEASUREMENTS AND MAIN RESULTS: Systemic
hemodynamic and oxygen transport variables were monitored. Tissue oxygen tensions
were measured in the liver and abdominal subcutaneous tissue layer. Gut
intramucosal pH (pHi) was determined, using a balloon tonometer. The animals were
divided into responders (n=9) and nonresponders (n=9) according to whether pHi
increased or decreased during resuscitation. Hemodynamic and oxygen transport
variables improved in the group of responders. In the group of nonresponders,
values decreased. Liver and subcutaneous oxygen tensions increased during the
initial phase of resuscitation in both groups but decreased after 30 mins in the
nonresponder group. CONCLUSIONS: The change in pHi during the first hour of
resuscitation could be used to divide animals treated uniformly from a
hemodynamic point of view into two distinct groups with seemingly different
outcome. The minimally invasive method could be of value for early evaluation of
the results of treatment of hemorrhagic shock.
PMID- 9635664
TI - Treatment of refractory intracranial hypertension with 23.4% saline.
AB - OBJECTIVE: To evaluate the effect of intravenous bolus administration of 23.4%
saline (8008 mOsm/L) on refractory intracranial hypertension (RIH) in patients
with diverse intracranial diseases. DESIGN: Retrospective chart review. SETTING:
A neurosciences intensive care unit in a university hospital. PATIENTS: We
present eight patients and a total of 20 episodes of increased intracranial
pressure (ICP) resistant to standard modes of therapy. Five patients had
subarachnoid hemorrhage, one patient had traumatic brain injury, one had a brain
tumor, and another had spontaneous basal ganglia hemorrhage. Seven patients had
intraventricular catheters, and one had a subarachnoid pressure screw placed. We
monitored continuously mean ICP, serum sodium concentrations, mean arterial
pressure, cerebral perfusion pressure (CPP), central venous pressure, and urine
output before and after the administration of hypertonic saline (HS). Post mortem
examination of the brain was performed in two patients. INTERVENTION: Intravenous
bolus administration of 30 mL of 23.4% saline. MEASUREMENTS AND MAIN RESULTS:
There was a significant (p < .05) decrease in ICP from a median of 41.5 mm Hg
before HS to 17 mm Hg at 1 hr, 16 mm Hg at 2 hrs, and 14 mm Hg at 3 hrs after HS
administration. In 80% of cases, ICP decreased by >50% of the pretreatment value
over a duration of 21.2+/-10.3 mins. ICP decreased to <20 mm Hg in 65% of all
cases and the mean time for it to again exceed 20 mm Hg was 6.3+/-4.9 hrs. There
was a significant improvement in CPP, from 64.7+/-19 (SD) mm Hg before HS to
85.6+/-18 mm Hg (1 hr) and 83+/-18 mm Hg (3 hrs) after HS. There were no
significant differences in the other variables measured. The post mortem
examinations showed no white matter changes or subdural collections. CONCLUSIONS:
This preliminary case series suggests that the intravenous bolus administration
of 23.4% saline reduces ICP and augments CPP in patients with resistant increased
ICP. This reduction can be maintained for several hours while other therapeutic
measures are being considered. The patient population most likely to respond to
this therapy needs to be further defined. Although more research is needed, this
treatment is promising as a new modality for RIH because of its ICP-lowering
effect without intravascular volume depletion.
PMID- 9635665
TI - Prognostic value of gastric intramucosal pH in critically ill children.
AB - OBJECTIVE: To determine the association of tonometrically measured gastric
intramucosal pH (pHi) to the occurrence of multiple organ dysfunction syndrome
(MODS) and death in critically ill children. DESIGN: Prospective, observational
study. SETTING: Pediatric intensive care unit (ICU) of a teaching children's
hospital. PATIENTS: Fifty-one critically ill children admitted (median age 5.4+/
5 [SD] yrs; range 1 mo to 16 yrs) with the following diagnoses: post major
surgery (n=26), sepsis (n=8), multiple trauma (n=5), acute respiratory distress
syndrome (n=4), and "miscellaneous" (n=8). INTERVENTIONS: Placement of a
tonometric catheter. MEASUREMENTS AND MAIN RESULTS: Pediatric Risk of Mortality
(PRISM) score and clinical data were collected on admission and pHi daily during
their stay in the pediatric ICU. A sigmoid tonometer was used to determine the
pHi. Unconditional logistic regression was used to investigate the prognostic
value of pHi. On admission, 26 patients presented with low gastric pHi (< or
=7.35) and 17 of them had values of <7.30. The mortality rate in children with
pHi <7.30 was 47.1% (95% confidence interval, 26.2 to 69) in contrast with an
11.7% mortality rate (95% confidence interval, 4.6 to 26.6) in children having a
pHi of > or =7.30 (p=.015). The pHi and PRISM score on admission were independent
predictive factors of death. The risk of mortality is increased when the pHi is
low (odds ratio=2.5). However, we did not find the pHi to be a predictor for
developing MODS. CONCLUSIONS: Our results show that pHi is an independent
predictor of mortality in patients admitted to a pediatric ICU. Although no
relationship was observed between the risk of MODS and gastric pHi, the
univariate difference of 21% vs. 41% is highly suggestive. The pHi determination
is a minimally invasive procedure and well tolerated in children of all ages.
PMID- 9635666
TI - Accuracy of two pulse oximeters at low arterial hemoglobin-oxygen saturation.
AB - OBJECTIVE: To evaluate the performance of two pulse oximeters in the measurement
of arterial hemoglobin saturation in hypoxemic children. DESIGN: Prospective,
repeated-measures observational study. SETTING: A 16-bed pediatric intensive care
unit in a children's tertiary hospital. PATIENTS: Sixty-six patients with
arterial saturation of <90%. INTERVENTIONS: Three arterial blood samples were
taken from each subject during a 48-hr period. Pulse oximeter measurements of
arterial saturation were compared with arterial saturation determined by
cooximetry. MEASUREMENTS AND MAIN RESULTS: Arterial saturation was measured using
one or both pulse oximeters (SpO2) and compared with the arterial hemoglobin
saturation determined by cooximetry (SaO2). Sixty-two subjects were studied,
using the Ohmeda pulse oximeter giving 185 data points (78 with saturations <75%
[defined by the average of pulse oximeter and cooximeter]); 53 subjects were
studied, using the Hewlett-Packard pulse oximeter yielding 155 data points (60
with saturations <75%). SpO2 ranged from 24% to 94%. Bias and precision of the
Ohmeda pulse oximeter were -2.8% and 4.8% >75% and -0.8% and 8.0% <75%. Bias and
precision of the Hewlett-Packard pulse oximeter were -0.5% and 5.1% >75% and 0.4%
and 4.6% <75%. Intrapatient regression coefficient (r) for the differences
between pulse oximeter and cooximeter was 0.58 for the Ohmeda and 0.59 for the
Hewlett-Packard. Regression coefficients for predicting change in cooximeter
value given a change in the Ohmeda pulse oximeter were 0.59 and 0.71 <75% and
>75%, respectively. Similar coefficients for the Hewlett-Packard pulse oximeter
were 0.50 and 0.70, respectively. CONCLUSION: The performance of the Ohmeda pulse
oximeter deteriorated below an SpO2 of 75%. The Hewlett-Packard pulse oximeter
performed consistently above and below an SpO2 of 75%. The ability of both pulse
oximeters to reliably predict change in SaO2 based on change in pulse oximetry
was limited. We recommend measurement of PaO2 or SaO2 for important clinical
decisions.
PMID- 9635667
TI - Nomenclature of endothelin peptides.
PMID- 9635668
TI - Evidence that humans produce less nitric oxide than experimental animals in
septic shock.
PMID- 9635669
TI - Therapy of myasthenic crisis.
PMID- 9635670
TI - Effects of NG-nitro-L-arginine-methyl-ester on cardiopulmonary function and
biosynthesis of cyclooxygenase products.
PMID- 9635671
TI - Prolonged extracorporeal life support for varicella pneumonia.
PMID- 9635672
TI - Smoke gets in your eyes.
PMID- 9635673
TI - Clear cell carcinoma of the endometrium is characterized by a distinctive profile
of p53, Ki-67, estrogen, and progesterone receptor expression.
AB - This study was designed to analyze certain clinicopathological features and the
profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression
of clear cell carcinoma of the endometrium and to determine whether the
pathogenesis of clear cell carcinoma can be accommodated by a dualistic model of
endometrial carcinogenesis. In this model, endometrioid carcinoma develops from
endometrial hyperplasia under unopposed estrogenic stimulation, and serous
carcinoma develops in atrophic endometrium from a putative precursor lesion
designated endometrial intraepithelial carcinoma (EIC). Twenty-one clear cell
carcinomas of the endometrium were analyzed and compared with 77 endometrioid
carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a
distinctive immunoprofile characterized by immunonegativity for ER and PR, low
immunoreactivity for p53, and a high Ki-67 proliferation index. ER, PR, and Ki-67
expression were similar to serous carcinoma, but p53 expression was significantly
lower in clear cell carcinoma (P < .05). ER and PR expression were significantly
lower, and the Ki-67 proliferation index was significantly higher in clear cell
carcinoma compared with endometrioid carcinomas (P < .05). p53 expression tended
to be higher in clear cell carcinoma compared with endometrioid carcinoma, but
the difference was not statistically significant. In contrast to endometrioid
carcinoma, clear cell carcinoma was rarely associated with endometrial
hyperplasia and serous carcinoma was not. Subdividing clear cell carcinoma
morphologically into one that resembled serous carcinoma (clear cell carcinoma
with serous features) and another that did not (typical clear cell carcinoma)
showed that clear cell carcinoma with serous features had a higher Ki-67
proliferation index than typical clear cell carcinoma, although expression of ER,
PR, and p53 were similar. Clear cell carcinoma with serous features was
associated with EIC in 50% and was not associated with endometrial hyperplasia.
In contrast, typical clear cell carcinoma was associated with endometrial
hyperplasia in 40% and was not associated with EIC. In summary, this study
provides evidence that clear cell carcinoma of the endometrium, like serous
carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In
contrast to serous carcinoma, strong p53 expression occurred less frequently in
clear cell carcinoma and predominantly in clear cell carcinoma with serous
features. The findings suggest that the molecular events that underlie the
development of clear cell carcinoma differ from those of endometrioid and serous
carcinoma.
PMID- 9635674
TI - Altered expression of the p53-regulated proteins, p21Waf1/Cip1, MDM2, and Bax in
ultraviolet-irradiated human skin.
AB - The distribution of p21WAf1/CiP1, MDM2, and Bax/Bcl-2 proteins in ultraviolet
(UV)-irradiated and nonirradiated human skin was examined immunohistochemically
and compared with p53 protein levels. Sun-protected buttock skin from three
volunteers was exposed to solar simulated irradiation, and biopsies were
performed 0.5, 1, 2, 4, and 24 hours after irradiation as well as control
unirradiated skin from the opposite buttock. A similar staining pattern was
observed in each of the three volunteers. P53 protein was detectable in all skin
samples examined. P21Waf1/CiP1 protein was visible in the nuclei of cells at 4
hours, and staining intensity increased at 24 hours. MDM2 protein expression was
noted in isolated nuclei in the epidermis at 24 hours. Bax cytoplasmic staining
was evident in the basal layer of the epidermis of all samples, and this staining
appeared to increase in intensity in the 4- and 24-hour specimens. There was no
Bcl-2 immunohistochemical staining in any sample. These results suggest that p53
and genes/proteins under the control of p53 are altered/ activated in normal
human skin in response to UV exposure.
PMID- 9635675
TI - Ret oncogene activation in papillary thyroid carcinoma: prevalence and
implication on the histological parameters.
AB - The Ret proto-oncogene is known to be rearranged in papillary carcinoma of the
thyroid. The aim of this study was to investigate the in situ expression of Ret
mRNA in thyroid tumors. Formalin-fixed, paraffin-embedded tissue specimens from
45 thyroid lesions were examined by in situ hybridization using manual capillary
action technology (MicroProbe Staining System) and a 52-base synthetic
biotinylated oligonucleotide probe complementary to the tyrosine-kinase domain of
Ret proto-oncogene. The clinicopathological features of these patients with
thyroid lesions also were noted. Ret was noted in 17 (43%) of 40 papillary
carcinomas. In contrast, none of the three follicular carcinomas, follicular
adenoma, nodular hyperplasia, and normal thyroids, showed evidence of Ret mRNA.
Our results showed that, in papillary thyroid carcinoma, there is an important
role of Ret activation. The Ret staining could be a useful marker for papillary
carcinoma.
PMID- 9635676
TI - Epstein-Barr virus-related posttransplantation lymphoproliferative disorder
involving pancreas allografts: histological differential diagnosis from acute
allograft rejection.
AB - The clinical and pathological features of acute pancreas allograft rejection and
involvement of the graft by posttransplantation lymphoproliferative disorders
(PTLD) overlap. Because the treatment is diametrically opposite in these two
types of lesions, an accurate diagnosis is essential. The histological features
in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4)
from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with
the material from 14 patients who did not develop PTLD after 12 to 58 months of
follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed
rejection-related heavy or atypical inflammatory infiltrates. Features typical of
rejection included most (>75%) being of mixed small and large, activated
appearing T lymphocytes, a smaller component of mature plasma cells, and variable
numbers of eosinophils. Cytologically atypical cells were always a minority (<
10%). The inflammation involved the septal spaces with proportional involvement
of the exocrine tissue, veins, ducts, and arteries. The inflammation was
particularly targeted against the acini and was associated with acinar cell
damage. Features characteristic of PTLD were nodular and expansile infiltrates,
composed of a significant proportion of atypical, plasmacytoid B cells (40% to
70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The
infiltrates involved the parenchyma randomly with no apparent affinity for the
acinar tissue. Extensive infiltration of the peripancreatic soft tissues was
common. Arterial walls were not involved in PTLD unless there was concurrent
acute vascular rejection. Features identified in both conditions were foci of
necrosis and infiltration of venous walls with associated endotheliitis. Samples
with concurrent PTLD and acute rejection showed combinations of these features.
In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in
the samples from patients with PTLD. Based on the assessment of morphological
differences and the selective use of relatively simple ancillary techniques, PTLD
can be correctly diagnosed even in small tissue samples such as needle biopsy
specimens. An early diagnosis will lead to the appropriate treatment.
PMID- 9635677
TI - Characterization of Coxsackie B virus RNA in myocardium from patients with
dilated cardiomyopathy by nucleotide sequencing of reverse transcription-nested
polymerase chain reaction products.
AB - This study was performed to detect and characterize the enterovirus present in
myocardium of some patients with heart muscle disease by nucleotide sequencing of
polymerase chain reaction (PCR) products after amplification with enterovirus
group-specific primers. Enterovirus sequences have been detected previously in
myocardium of patients with myocarditis or dilated cardiomyopathy and seem
causal, although the particular virus serotypes involved have not been
identified. In a prospective study of endomyocardial biopsy specimens from 35
consecutive patients with suspected heart muscle disease, enterovirus sequences
from the 5' nontranslated region were amplified by reverse transcription-nested
PCR using group-specific primers. This region contains both conserved and
variable sequence motifs, characteristic of particular enterovirus serotypes. The
nucleotide sequences of individual PCR products were determined by cycle
sequencing and compared with all known sequences (GenBank/EMBOL), using the GCG
software package. Endomyocardial biopsy specimens from 9 of 21 (42.9%) patients
with a histologically confirmed diagnosis of dilated cardiomyopathy were positive
for enterovirus by PCR, compared with only 1 of 14 (7.1%) patients with other
myocardial pathological conditions (Fisher's exact probability=0.0275: odds
ratio=9.75; 95% confidence interval=1.31-72.78). The nucleotide sequence of the
PCR products differed, indicating no cross-contamination. However, computerized
comparison showed that each had greatest homology with the 5' nontranslated
region of Coxsackie B virus but contained up to 11% sequence variations compared
with the prototype Coxsackie B3 strain Nancy. Parallel investigation of tissue
from our mouse model of Coxsackievirus B3-induced myocarditis showed that
nucleotide sequence changes are not introduced by reverse transcription or PCR.
These data support the link between enteroviral infection and dilated heart
muscle disease and suggest that Coxsackie B serotypes are the enteroviruses most
frequently involved.
PMID- 9635678
TI - Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests
ongoing mutation.
AB - Splenic marginal zone lymphoma (SMZL) is a low-grade primary splenic B cell
lymphoma, originally thought to be related to splenic marginal zone B cells.
Later studies showed that SMZL sometimes may be accompanied by villous
lymphocytes in the peripheral blood, a condition previously characterized as
splenic lymphoma with villous lymphocytes (SLVL). The relationship between SMZL
and splenic marginal zone B cells has recently been called into question. We
report four further cases of SMZL, two of which were associated with villous
lymphocytes in the peripheral blood. In addition to immunophenotypical analysis,
we have studied the IgV(H) genes in each case, because the extent and patterns of
their mutation can indicate the normal B cell counterpart of lymphomas. The
IgV(H) genes in the four cases of SMZL studied are mutated, which is consistent
with their origin from postfollicular marginal zone B cells. Evidence of ongoing
mutation was also observed. This contrasts with a study showing that blood-borne
tumor cells in SLVL show no sign of ongoing mutation. It is possible that the
ongoing mutations in the cases studied here are acquired in a splenic
microenvironment, such as that found in the follicle center.
PMID- 9635679
TI - MDR1 expression is associated with adverse survival in melanoma of the uveal
tract.
AB - Metastatic uveal melanoma is profoundly chemoresistant and has a very poor
outcome. We have previously shown that the MDR1 gene and its gene product P
glycoprotein (P-gp), which are known to cause drug resistance in cancer cells,
are expressed in ocular melanoma. Overexpression of MDR1 has been associated with
a poor survival in some tumor types treated by chemotherapy and in some untreated
tumours. To assess whether MDR1 expression is of prognostic value in uveal
melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108
cases. Three semiquantitative grades were used to evaluate positive staining. We
detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade
II staining; and 22%, grade III staining. There was a statistically significant
association (P=.004) between MDR1 expression by tumor cells and shorter survival
times (n=96), which was most striking at grade III levels of expression.
Multivariate analysis showed that MDR1 expression is an independent prognostic
indicator of poor survival. We conclude that (1) MDR1 may be involved in
chemoresistance and tumor propagation in primary uveal melanoma, and (2)
increasing levels of expression are prognostically significant and may prove a
useful marker of tumor invasiveness, independent of established prognostic
factors.
PMID- 9635680
TI - Telomerase expression in gliomas including the nonastrocytic tumors.
AB - Telomerase is a ribonucleoprotein that consists of a RNA component for
synthesizing telomeric DNA repeats onto chromosome ends, so that telomere length
can be maintained; telomerase activation in general signifies immortalization of
cells. Because the telomerase activity of only a few cases of nonastrocytic
gliomas and low-grade astrocytic gliomas have been examined before, telomerase
activity from a broad spectrum of astrocytic and nonastrocytic gliomas were
examined in this study. A total of 119 brain tumor samples, including 16
pilocytic astrocytomas, one dysembryoplastic neuroepithelial tumor (DNT), two
pleomorphic xanthoastrocytomas (PXA), 15 ependymomas, 21 oligodendrogliomas, 13
grade II astrocytomas, 13 anaplastic astrocytomas, and 38 glioblastoma multiforme
tumors (GBM), were studied, using a polymerase chain reaction (PCR)-based
telomeric repeat amplification protocol assay. All pilocytic astrocytomas, DNT,
PXA, and myxopapillary ependymomas were telomerase negative. Three of 13 (15.4%)
classical ependymomas, 2 of 14 (14.3%) grade II oligodendrogliomas, and three of
seven (42.9%) anaplastic oligodendrogliomas had detectable telomerase activity.
The frequency of telomerase expression in ependymomas and oligodendrogliomas was
lower than those observed in astrocytic tumors: fibrillary astrocytoma, 23.1%;
anaplastic astrocytoma, 23.1%; and GBM, 26.3%. The mean age of telomerase
positive GBM patients (61.7 years) was significantly higher than that of
telomerase-negative GBM patients (47.8 years, P=.002). These results suggest that
telomerase activation may occur early in glial tumorigenesis, and astrocytomas
may have mechanisms of immortalization other than telomerase activation.
PMID- 9635681
TI - Allelic loss on chromosome 22q in epithelioid sarcomas.
AB - Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially
aggressive, clinical behavior. Distinction from other benign and malignant
entities may be a diagnostic dilemma. In this study, we evaluate the presence of
loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid
sarcomas, four epithelioid angiosarcomas, and two epithelioid
hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was
detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss
was detected in the informative vascular tumors, three angiosarcomas, and two
hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor
gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or
mutated in some NF2-related tumors, sporadic meningiomas, and vestibular
schwannomas, as well as a few other tumors. Our data suggest that a region of
chromosome 22q may be the locus of a tumor suppressor gene involved in the
tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor
suppressor genes in this region, or even the NF2 tumor suppressor gene, may play
a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected
in epithelioid sarcomas and not in the vascular tumors studied suggests a
possible role for this marker in diagnosis.
PMID- 9635682
TI - Distinction of basaloid squamous cell carcinoma from adenoid cystic and small
cell undifferentiated carcinoma by immunohistochemistry.
AB - Basaloid squamous cell carcinoma (BSCC) is a recently recognized variant of
squamous cell carcinoma (SCC) with a predilection to occur in the tongue base,
hypopharynx, and supraglottic larynx. In smal biopsy specimens, these tumors can
be difficult to distinguish from small cell undifferentiated carcinoma (SCUC) and
adenoid cystic carcinoma (ACC). Monoclonal antibodies reactive with cytokeratin
(AE1/AE3, 34betaE12, Cam 5.2) as well as a variety of other cellular antigens
(vimentin, actin, desmin, chromogranin, synaptophysin, CD57, neuron-specific
enolase [NSE], and S100) were used in an immunoperoxidase method with paraffin
embedded tissue to phenotypically characterize 23 cases of BSCC, 10 cases of
SCUC, and 15 cases of ACC. The neoplastic cells in 22 of the 23 cases of BSCC
reacted with the high-molecular-weight cytokeratin antibody 34betaE12, whereas no
reactivity was seen in any of the 10 cases of SCUC. This pattern of 34betaE12
reactivity more consistently differentiated BSCC from SCUC than did reactivity
with the neuroendocrine markers chromogranin, synaptophysin, CD57, and NSE. These
findings show that immunoperoxidase stains performed on paraffin-embedded tissue
are potentially useful in establishing a diagnosis of basaloid squamous cell
carcinoma.
PMID- 9635683
TI - Loss of p53 function in uterine papillary serous carcinoma.
AB - In contrast to endometrioid carcinoma, uterine papillary serous carcinoma (UPSC)
is an aggressive type of endometrial cancer. Loss of p53 function is critical for
the molecular pathogenesis of UPSC. Both UPSC and its putative precursor,
endometrial intraepithelial carcinoma (EIC), show abnormal p53 overexpression in
most tumors. To further assess the nature of p53 alterations in UPSC, we
systematically reevaluated a subset of our previous cohort of UPSC patients. In
the current study, we correlate mutations of the p53 gene as detected by direct
sequencing of exons 5 through 8 with p53 accumulation and expression of Waf-1 in
32 UPSC tumors. Waf-1 is a downstream effector of p53-mediated G1 arrest after
DNA damage and, thus, an indicator of p53 functionality. Although 78% of tumors
exhibited strong nuclear p53 immunoreactivity in 100% of tumor cells, we were
able to detect p53 mutations in 53%. As expected, all p53 mutant tumors (17
cases) exhibited p53 overexpression. Seventy percent of those (12 tumors) showed
concomitant lack of Waf-1 expression consistent with transcriptionally inactive
p53, whereas the other five tumors showed Waf-1 staining in only a minor fraction
of tumor cells consistent with p53-independent Waf-1 expression. In contrast, 47%
(15 cases) of tumors failed to exhibit p53 mutations; interestingly, more than
half of those (eight cases) showed strong nuclear p53 accumulation in all tumor
cells but lacked concomitant Waf-1 expression. These findings are consistent with
a mutation-dependent and -independent type of p53 inactivation in UPSC that are
both associated with nuclear overexpression. Our findings suggest that the
combined immunocytochemical analysis of p53 and Waf-1 is a valuable means of
assessing the functional status of p53. In summary, p53 alterations are common in
UPSC and probably responsible for its aggressive biological behavior.
PMID- 9635684
TI - Digital image analysis of proliferative index: two distinct populations of high
grade prostatic intraepithelial neoplasia in close proximity to adenocarcinoma of
the prostate.
AB - A considerable amount of data has been collected showing the association of high
grade prostatic intraepithelial neoplasia (HGPIN) with adenocarcinoma of the
prostate, and many studies have yielded results that suggest that HGPIN is a
precursor of carcinoma. A few studies have indicated that HGPIN may, in some
cases, be a sequela of prostatic adenocarcinoma. We examined the proliferative
indices of HGPIN, carcinoma, and benign prostatic epithelium by computer-aided
counting of Ki-67-positive nuclei in 15 cases in which HGPIN and carcinoma were
in close proximity. There were 13 radical prostatectomy specimens with prostate
cancer and two cystoprostatectomy specimens with both transitional cell carcinoma
and prostatic adenocarcinoma. First, we showed the accuracy of the computer-aided
counting method compared with direct counting through the binoculars of the
microscope. Then proliferative activity was assessed for each case by picking the
two areas of carcinoma, the two areas of HGPIN, and the one area of benign
epithelium with the greatest density of carcinomatous, dysplastic, and benign Ki
67-positive nuclei, respectively. The total number of nuclei and the number of
positive nuclei were counted. Basal cells were not counted. The mean
proliferative index was higher for cancer (caindex, average 0.054) than for HGPIN
(pinindex, average 0.048) (P < .05). We found that the 15 cases fell into two
distinct groups. The average ratio of pinindex to caindex (pinindex/caindex) was
lower in group 1 (0.72) than in group 2 (1.54) (P=.17), and when the results were
corrected for the nonzero gamma-intercepts of the regression lines of pinindex
versus caindex, the ranges were widely separated, and the difference between the
means was statistically significant (0.15 v 0.62; P < .0001). A greater
subjective similarity between the nuclear features in the HGPIN and those of the
corresponding carcinoma was noted for the cases in group 2. The average value of
bngnindx was 0.014. The value of bngnindx did not correlate with either caindex
or pinindex. We conclude that there may be two types of lesions with the
morphological appearance of HGPIN and that they may have different relationships
to carcinoma. Computer-aided counting of digitized microscopic images is both
labor-saving and as accurate as enumeration directly through the binoculars of
the microscope.
PMID- 9635685
TI - CD44V6 expression in human colorectal carcinoma.
AB - CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix
interactions. This transmembrane glycoprotein exists in either standard or
variant forms, originated by alternative splicing. One of the isoforms (CD44V6)
has been shown, in some systems, to modify the metastatic potential of tumor
cells. To investigate the role of this biomarker as possible prognostic antigen
in colorectal cancer, we immunohistochemically analyzed the distribution of
CD44V6 expression on formalin-fixed, paraffin-embedded tissues from resected
colorectal cancers of 34 patients. The monoclonal antibody VFF7 against the amino
acid sequence encoded by exon CD44V6 was applied using the avidin-biotin
peroxidase method. For each resected specimen, normal (N), adenomatous (AD), and
carcinomatous (CA) colonic mucosa were tested. In 68% of the resected cases,
these areas were present in the same slide, and in 76% of cases, nodal or liver
metastases (MT) were available for evaluation. Adenomatous polyp biopsy specimens
of 10 carcinoma-free patients were also tested. In selected cases, CD44V6
expression was also determined using the Western blot immunoprecipitation
technique. CD44V6 immunoreactivity was detected in 100% of the ADs, and in 91% of
CAs, but was mostly weak in only 38% of MTs (n=26). In 49% (n=35) of ADs, 11%
(n=34) of CAs, and 4% of MTs (n=26), the stain was moderate to strong. CD44V6
immunoreactivity was predominantly membranous in ADs and cytoplasmic in MTs. In
the CAs, both staining patterns were noted. Interestingly, the normal mucosa had
a weak subnuclear localization of the stain. In the cases evaluated by Western
blotting immunoprecipitation analysis, the level of CD44V6 protein expression was
similar to that obtained by immunohistochemistry. No correlation was found with
tumor type, stage, or patient survival. The predominant CD44V6 expression in ADs
and CAs, but not in MTs, suggests that, in many cases, the expression of this
adhesion molecule may be lost during the acquisition of migratory function by the
tumor cells.
PMID- 9635686
TI - The histological spectrum of hemangiopericytoma: application of
immunohistochemical analysis including proliferative markers to facilitate
diagnosis and predict prognosis.
AB - Hemangiopericytoma (HPC) is an uncommon vascular neoplasm thought to be derived
from pericytes. Prediction of patient outcome is difficult based what is
currently known about these tumors and histological parameters alone. We compiled
27 cases of HPC and evaluated the spectrum of histological features to
investigate whether there was any correlation between histology, immunostaining,
prognostic markers, and patient outcome. The following parameters were evaluated:
vasculature, histological pattern (solid, myxoid, trabecular, alveolar), degree
of cellular pleomorphism, necrosis, mitoses, and giant cell content.
Immunohistochemistry was performed to determine the reactivity for CD 31, CD34,
vimentin, actin, cytokeratin, S100, actin, and SMA. Proliferative rate was
analyzed using antibodies to PCNA and MIB1. Patient's age ranged from 8 months to
75 years (mean, 35; median, 31). Twenty of 27 cases were located in the
extremities. The tumors were grossly described as lobulated and well
circumscribed (n=12) and nonencapsulated (n=15). By histology, the characteristic
ramifying or staghorn vasculature pattern was seen in all cases. A solid
histological pattern was mixed with an alveolar pattern in three cases,
trabecular pattern in six cases, and myxoid pattern in two cases. Tumor cells
were uniform, polygonal to spindle-shaped, often with vesicular nuclei. Tumor
giant cells were present in 9 of 27 cases; necrosis, in 11 of 27. Mitoses ranged
from 0 to 14 per 10 high-power fields (HPF). Cellular pleomorphism was 1+ in nine
cases, 2+ in 12 cases, and 3+ in six cases. Immunohistochemistry showed
reactivity for CD34 and vimentin in all cases. Actin was focally positive in one
case, and SMA was focally positive in another. CD 31, cytokeratin, and S100 were
uniformly nonreactive. Proliferative index measured by PCNA and MIBI ranged
between less than 1% and 40% of tumor cells. Follow-up was available in 22 cases
and ranged from 1 year to 15 years. Seven patients had metastases, and two
recurred locally. Thirteen patients had no evidence of disease at last checkup.
Parameters associated with recurrences or metastases include a trabecular
pattern, the presence of necrosis, mitoses, vascular invasion, and cellular
pleomorphism. Features associated with an aggressive biological behavior can be
identified histologically. There was some, but not total, correlation between
proliferative markers and tumor aggressiveness.
PMID- 9635687
TI - Papillary immature metaplasia (immature condyloma) of the cervix: a
clinicopathologic analysis and comparison with papillary squamous carcinoma.
AB - Papillary immature metaplasia (PIM) is a variant of human papillomavirus (HPV) 6
or 11 infection. PIM resembles an immature metaplasia but has filiform papillae,
variable cytological atypia, and, frequently, extension into the endocervical
canal. Because the unusual morphology and presentation of PIM may cause confusion
between this and other benign and malignant papillary neoplasms, we conducted a
clinicopathologic analysis of PIM and compared expression of Ki-67 between PIM,
condyloma, and papillary carcinoma. Data on patient age, duration of the lesions,
and procedures, including cone biopsy, were obtained. The distribution and
intensity of staining for Ki-67 in the epithelium was recorded and compared with
both condyloma and papillary carcinoma. HPV typing was performed by polymerase
chain reaction (PCR) and restriction fragment length pleomorphism analysis
(RFLP). Ten of 13 PIMs were HPV 6/11 positive. Three cases contained areas
closely resembling condyloma. Eleven cone biopsies were performed on nine cases.
Three were found to have a coexisting high-grade squamous intraepithelial lesion
that was either HPV 6/11 negative or contained another HPV type. All PIMs
displayed variable staining for Ki-67 with a low index of staining in the mid and
upper epithelial layers. In contrast, areas of condyloma had significantly
stronger staining in areas with viral cytopathic effect (koilocytosis). Six
papillary carcinomas were analyzed and displayed moderate to diffuse staining,
including staining of the superficial cell nuclei. PIM is a distinct pathological
subset of cervical condyloma that frequently is managed by cone biopsy and may
persist. The marked reduction in Ki-67 staining in superficial cell layers
distinguishes PIM from some condylomata and most HSILs and papillary carcinomas.
Immunostaining thus may be helpful in distinguishing PIM from papillary
carcinoma, although the differentiation of the two is best made on morphological
grounds.
PMID- 9635688
TI - Cat-scratch disease simulating Histiocytosis X.
AB - Cat-scratch disease is a self-limited condition commonly causing a benign chronic
lymphadenopathy in children. Osteolytic lesions are a rare complication, but have
been previously reported. We report a case of a solitary osteolytic lesion of the
skull whose clinical, radiographic and pathological features were initially
interpreted as being consistent with Histiocytosis X. Subsequently, positive
serological titers for Bartonella, a history of a cat-scratch antecedent to the
onset of clinical symptoms and review of the original histopathology confirmed
the diagnosis of cat-scratch disease. We reviewed the English language literature
on osteolytic lesions associated with cat-scratch disease and compare the current
case with those previously reported.
PMID- 9635689
TI - Massive macrophage lipid accumulation presenting as hepatosplenomegaly and
lymphadenopathy associated with long-term total parenteral nutrition therapy for
short bowel syndrome.
AB - We present a unique case of massive splenomegaly, hepatomegaly, and
lymphadenopathy caused by lipid-laden macrophages in a 50 year old white female
with short-bowel syndrome treated with long-term total parenteral nutrition.
Using transmission electron microscopy and special stains we were able to show
that the total parenteral nutrition lipid component was composed of lipid
droplets and micelles morphologically identical to those found in lipid-laden
macrophages which had accumulated in the patient's reticuloendothelial system
leading to massive splenomegaly, hepatomegaly (without evidence of steatosis) and
lymphadenopathy. While this phenomenon has been reported in animal models, no
human cases have been previously reported.
PMID- 9635690
TI - Primary aneurysmal cyst of soft tissue: serial magnetic resonance imaging study.
PMID- 9635691
TI - Malignant mesothelioma presenting as colonic tumor.
PMID- 9635692
TI - Bronchiolitis obliterans, Castleman's disease, and a bullous disease: pemphigus
vulgaris or paraneoplastic pemphigus?
PMID- 9635693
TI - Dose escalation with three-dimensional conformal radiation therapy affects the
outcome in prostate cancer: will more prove better?
PMID- 9635694
TI - Dose escalation with three-dimensional conformal radiation therapy affects the
outcome in prostate cancer.
AB - PURPOSE: Three-dimensional conformal radiation therapy (3D-CRT) is a technique
designed to deliver prescribed radiation doses to localized tumors with high
precision, while effectively excluding the surrounding normal tissues. It
facilitates tumor dose escalation which should overcome the relative resistance
of tumor clonogens to conventional radiation dose levels. The present study was
undertaken to test this hypothesis in patients with clinically localized prostate
cancer. METHODS AND MATERIALS: A total of 743 patients with clinically localized
prostate cancer were treated with 3D-CRT. As part of a phase I study, the tumor
target dose was increased from 64.8 to 81 Gy in increments of 5.4 Gy. Tumor
response was evaluated by post-treatment decrease of serum prostate-specific
antigen (PSA) to levels of < or = 1.0 ng/ml and by sextant prostate biopsies
performed > or = 2.5 years after completion of 3D-CRT. PSA relapse-free survival
was used to evaluate long-term outcome. The median follow-up was 3 years (range:
1-7.6 years). RESULTS: Induction of an initial clinical response was dose
dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadir <
or = 1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy,
respectively (p < 0.001). The 5-year actuarial PSA relapse-free survival for
patients with favorable prognostic indicators (stage T1-2, pretreatment PSA < or
= 10.0 ng/ml and Gleason score < or = 6) was 85%, compared to 65% for those with
intermediate prognosis (one of the prognostic indicators with a higher value) and
35% for the group with unfavorable prognosis (two or more indicators with higher
values) (p < 0.001). PSA relapse-free survival was significantly improved in
patients with intermediate and unfavorable prognosis receiving > or = 75.6 Gy (p
< 0.05). A positive biopsy at > or = 2.5 years after 3D-CRT was observed in only
1/15 (7%) of patients receiving 81.0 Gy, compared with 12/25 (48%) after 75.6 Gy,
19/42 (45%) after 70.2 Gy, and 13/23 (57%) after 64.8 Gy (p < 0.05). CONCLUSIONS:
The data provide evidence for a significant effect of dose escalation on the
response of human prostate cancer to irradiation and defines new standards for
curative radiotherapy in this disease.
PMID- 9635695
TI - Dose escalation with 3D conformal treatment: five year outcomes, treatment
optimization, and future directions.
AB - PURPOSE: To report the 5-year outcomes of dose escalation with 3D conformal
treatment (3DCRT) of prostate cancer. METHODS AND MATERIALS: Two hundred thirty
two consecutive patients were treated with 3DCRT alone between 6/89 and 10/92
with ICRU reporting point dose that increased from 63 to 79 Gy. The median follow
up was 60 months, and any patient free of clinical or biochemical evidence of
disease was termed bNED. Biochemical failure was defined as prostate-specific
antigen (PSA) rising on two consecutive recordings and exceeding 1.5 ng/ml.
Morbidity was reported by the Radiation Therapy Oncology Group (RTOG) scale, the
Late Effects Normal Tissue (LENT) scale, and a Fox Chase modification of the
latter (FC-LENT). All patients were treated with a four-field technique with a 1
cm clinical target volume (CTV) to planning target volume (PTV) margin to the
prostate or prostate boost; the CTV and gross tumor volume (GTV) were the same.
Actuarial rates of outcome were calculated by Kaplan-Meier and cumulative
incidence methods and compared using the log rank and Gray's test statistic,
respectively. Cox regression models were used to establish prognostic factors
predictive of the various measures of outcome. Five-year Kaplan-Meier bNED rates
were utilized by dose group to estimate logit response models for bNED and late
morbidity. RESULTS: PSA <10 ng/ml: No dose response was demonstrated using
estimated bNED rates or by analysis of PSA nadir vs. dose. PSA 10-19.9 ng/ml: A
bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit
response model showed 5-year bNED rates of 35% at 70 Gy and 75% at 76 Gy (p =
0.0049) and illustrated the relative ineffectiveness of conventional dose
treatment. PSA 20+ ng/ml: A bNED dose response was demonstrated (p = 0.02) using
the log rank test. The logit response model indicated a 5-year bNED rate of 10%
at 70 Gy and 32% at 76 Gy (p = 0.10). Morbidity: Dose response was demonstrated
for FC-LENT grade 2 and grade 3,4 GI morbidity and for LENT grade 2 GU sequelae.
RTOG grade 3,4 GI morbidity at 5 years was <1%. Factors associated with bNED,
cause-specific survival, and metastasis were studied using Cox multivariate
analysis. Pretreatment PSA (p = 0.0001), Gleason score 7-10 (p = 0.0001), and
dose (p = 0.017) were significantly predictive of bNED. For each 1 Gy increase in
dose, the hazard of bNED failure decreased by 8%. Palpation stage was associated
with cause-specific survival (p = 0.002) and distant metastasis (p = 0.0004).
Gleason score was also predictive of distant metastasis (p = 0.02). CONCLUSIONS:
A dose response was observed for patients with pretreatment PSA >10 ng/ml based
on 5-year bNED results. No dose response was observed for patients with
pretreatment PSA < 10 ng/ml. Dose response was observed for FC-LENT grade 2 and
grade 3,4 GI sequelae and for LENT grade 2 GU sequelae. Optimization of treatment
was made possible by the results in this report. The improvement in 5-year bNED
rates for patients with PSA levels > 10 ng/ml strongly suggests that clinical
trials employing radiation should investigate the use of 3DCRT and prostate doses
of 76-80 Gy.
PMID- 9635696
TI - Changes in biochemical disease-free survival rates as a result of adoption of the
consensus conference definition in patients with clinically localized prostate
cancer treated with external-beam radiotherapy.
AB - PURPOSE: The optimal definition of biochemical recurrence of prostate cancer
after definitive radiotherapy remains elusive. Different institutions have
developed their own definitions, and a consensus conference (CC) sponsored by the
American Society for Therapeutic Radiology and Oncology has recently proposed
another definition. This study compares the definition previously used at our
institution with the definition proposed by the CC. METHODS: Two hundred and
eight patients were treated for localized prostate cancer with conformal external
beam radiotherapy between 1989-1993 at our institution and followed for at least
24 months. Patients were categorized as failures according to our institutional
definition and the CC definition. Our definition (CPMC) required two increases in
serum prostate specific antigen (PSA) over at least a 3-month period with a final
value of at least 1 ng/ml or a single value resulting in clinical intervention.
The CC definition required three consecutive increases in PSA. This was modified
to also consider those patients with one or two increases leading to clinical
intervention as failures. Differences in the failure rates between the two
definitions were evaluated and factors influencing these differences were
explored. In an additional analysis, CC was modified such that patients with one
or two PSA increases were censored at the time of the PSA prior to the increases
(CC-II), rather than at the last PSA (CC). The median follow-up time was 31
months. RESULTS: There were 36 fewer failures according to CC (n = 96) compared
with CPMC (n = 132) (p < 0.001). Twenty cases called failures by CPMC
subsequently had a decrease in PSA ("false failures"). The other 16 patients have
had two increases in PSA, but are awaiting their next follow-up visit to obtain a
third PSA ("pending failures"). Analysis of factors predicting "pending failures"
showed Gleason score to be the sole predictor of this change in status in
multivariate analysis (p = 0.03) with patients with lower-grade tumors being more
likely to change status (Gleason 2-6: 15% vs. Gleason 7-10: 1%). On the other
hand, "false failures," compared to true failures, had a lower mean PSA nadir
(1.7 ng/ml vs. 7.0 ng/ml, p < 0.001) and significantly smaller mean increases in
PSA (1st increase: 0.6 ng/ml vs. 3.4 ng/ml, p = 0.006; 2nd increase: 0.4 ng/ml
vs. 4.8 ng/ml, p = 0.002). In 85% (17 of 20) of these patients, at least one of
the increases was < or = 0.3 ng/ml compared with 44% (42 of 96) of the true
failures (p = 0.0008). CC-II resulted in a small decrease in BDFS rates compared
with CC, but did not affect the overall difference between CC and CPMC. A
modified definition that defines failure as two consecutive increases in PSA over
3 months, with a final value greater than 1.0 ng/ml and each increase being at
least 0.3 ng/ml, or three consecutive increases would result in a "false" failure
rate of only 3% (3 of 99) and identify 56% (54 of 96) of the true failures after
only two PSA increases. CONCLUSION: The CPMC definition of two PSA increases can
falsely identify patients as failures, particularly if the increases in PSA are
small (i.e., < or = 0.3 ng/ml). The CC definition requiring three increases in
PSA can falsely identify patients as disease-free when the time to failure is
long relative to the follow-up time. We propose a that a definition that combines
aspects of both definitions (two consecutive increases in PSA over 3 months, with
a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml,
or three consecutive increases) may be a better definition of biochemical
failure.
PMID- 9635697
TI - The treatment of nonpalpable PSA-detected adenocarcinoma of the prostate with 3
dimensional conformal radiation therapy.
AB - PURPOSE: We reviewed our institution's experience treating patients with
nonpalpable PSA-detected prostate cancer with three-dimensional conformal
radiation therapy (3DCRT) to determine prognostic factors that predict for
biochemical-free survival (bNED) control and present the bNED control rates.
METHODS AND MATERIALS: Between May 1, 1990 and November 30, 1994, 160 patients
with nonpalpable PSA-detected prostate cancer received 3DCRT at Fox Chase Cancer
Center (median total dose 73 Gy; range: 67-78 Gy). bNED failure was defined as
three consecutive increases in posttreatment PSA after achieving a nadir. bNED
failure was recorded as the time midway between the nadir and the first
consecutive rising PSA. Five-year actuarial rates of bNED control were calculated
for pretreatment PSA (0-9.9 vs. 10-19.9 vs. > or = 20 ng/ml), Gleason score (2-6
vs. 7-10), treatment field size (prostate vs. small pelvis), age (<65 vs. > or =
65), and dose (< or = 73 vs. >73 Gy) using Kaplan-Meier methods and compared
using the Log rank test. The Cox model was used to multivariately establish
independent predictors based on significant univariate factors. Median follow-up
was 39 months (range: 2-84 months). RESULTS: The 5-year actuarial rate of bNED
control was 86% for the entire group of patients. The Cox Proportional Hazards
model demonstrated that pretreatment PSA was an independent predictor of bNED
control. Treatment field size was marginally predictive. There was no difference
in bNED control when patients were stratified by the number of lobes positive for
disease. Statistically different rates of bNED control were seen when the
patients with nonpalpable disease were univariately compared to T2b and T2c
patients. Three patients experienced Grade 3-4 genitourinary (GU) toxicity and 3
patients experienced Grade 3-4 gastrointestinal (GI) toxicity. CONCLUSIONS:
Patients with nonpalpable PSA-detected prostate cancer can be effectively treated
with 3DCRT with minimal morbidity and high rates of bNED control at 5 years.
Pretreatment PSA level is an independent predictor of bNED control.
PMID- 9635698
TI - High dose-rate afterloading 192Iridium prostate brachytherapy: feasibility
report.
AB - BACKGROUND: RESULTS from localized prostate cancer series using seed implants
have been most encouraging. However, with current techniques, inadequate
dosimetry sometimes occurs. Remote afterloading high dose rate 192Iridium
brachytherapy (HDR-Ir192) theoretically remedies some potential inadequacies of
seed implantation by performing the dosimetry after the needles are in place.
This study was undertaken to determine the feasibility of incorporating
multifractionated HDR-Ir192 in the brachytherapy management of prostate
carcinoma. METHODS: From October 1989 to August 1995, 104 patients were treated
with a combination of multifractionated HDR-Ir192 and external beam. Patients
ranged in age from 48-78 years, with a mean of 68.6 years. By TNM clinical stage,
there were 1 T1b, 31 T1c, 28 T2a, 24 T2b, 9 T2c, 8 T3a, and 3 T3c lesions. For
the group, the mean initial pretreatment PSA was 12.9 ng/ml (median 8.1), with
90% of the patients having had a pretreatment PSA greater than a normal value of
4.0 ng/ml. Patients with prostate volumes up to 105 cc were implanted. Treatment
was initiated with perineal needle placement using ultrasound guidance. A
postoperative CT scan was obtained to provide the basis for treatment planning.
Four HDR-Ir192 treatments were given over a 40-h period, with a minimal
peripheral dose (MPD) ranging from 3.00 to 4.00 Gy per fraction over the course
of this study. Two weeks later, external beam radiation was added using 28
fractions of 1.80 Gy daily, to a dose of 50.40 Gy. RESULTS: Follow-up ranged from
10 to 89 months, with a mean of 46 months and median of 45 months. At various
follow-up points, the patient numbers at risk were: 1 year, 101; 3 years, 69; 5
years, 28. The technique proved to be uniformly applicable to a wide range of
prostate volumes and was very well tolerated by patients. Nearly all significant
late in-field treatment complications were genitourinary in nature. Of the
patients, 6.7% developed urethral strictures that were readily manageable.
Changes in technique implemented in 1993 appear to have significantly lessened
the incidence of this complication. Two patients developed significant uropathy
within the first treatment year, but both resolved; 1 of these 2 patients had a
prior TURP. Other bladder or rectal complications have been minimal. Using PSA
progression as a marker of tumor response, approximately 84% of patients whose
initial PSA was less than 20 ng/ml were free of progression at 5 years by
actuarial analysis. CONCLUSIONS: We found the use of transperineal
ultrasonography, postimplant CT-based dosimetry, coupled with adjustable dose
delivery inherent to remote afterloading technology, to give unparalleled control
in performing this complex brachytherapy task. Thus, it may be advantageous in
certain clinical situations where the resultant MPD is needed to reliably cover
the target volume, such as in patients with carcinomas at base locales, when the
possibility of moderate to extensive intraprostatic tumor exists, and in patients
with large glands. Early PSA data suggest that it may be effective as a
definitive treatment with rates of adverse late tissue effects that are
acceptable using current technique and doses described herein. Longer follow-up
is needed to ascertain its position among the various treatment regimens for
prostate carcinoma.
PMID- 9635699
TI - Carcinoma of the urethra in women.
AB - PURPOSE: This analysis was performed to evaluate the influence of clinical and
treatment factors on local tumor control, survival, and complications for women
with urethral carcinoma. METHODS AND MATERIALS: The records of 44 women with
carcinoma of the urethra were reviewed. Their age ranged from 37 to 89 years
(mean, 67 years). Mean follow-up time was 8.25 years. The stages of disease were
T1 in eight, T2 in five, T3 in 22, and T4 in nine. Treatment was with surgery in
7, radiotherapy in 25, and combined surgery and radiotherapy in 12. RESULTS: The
5-year overall survival was 42% and the 5-year cause-specific survival was 40%.
At the time of last follow-up, 11 women were alive and 33 were dead. Recurrence
of tumor occurred in 27 women and was the cause of death for 23. Recurrence was
local in 8, local and distant in 15, and distant in 4. Severe complications
occurred in nine women (20%). The severe complication rate was 29% (2 of 7) for
women treated with surgery, 24% (6 of 25) for women treated with radiotherapy,
and 8% (1 of 12) for women treated with surgery and radiotherapy. A multivariate
analysis was performed to evaluate the interaction of tumor size, histology, and
location, and lymph node status. This analysis indicated that tumor size and
histology were independent prognostic factors for survival and local tumor
control. Adenocarcinoma occurred in 13 women, and none of them were alive at 5
years. Only 1 of 10 women with tumors greater than 4 cm was alive at 5 years.
CONCLUSIONS: The most significant clinical factors affecting prognosis were tumor
size and histology. Tumor location was not an independent prognostic variable.
None of the women with adenocarcinoma, and only one woman with a tumor greater
than 4 cm was alive at 5 years, irrespective of modality of treatment. Aggressive
treatment resulted in a high complication rate.
PMID- 9635700
TI - A randomized study of two doses of abdominopelvic radiation therapy for patients
with optimally debulked Stage I, II, and III ovarian cancer.
AB - PURPOSE: To determine whether an increased dose of abdominal radiation therapy
results in improved disease control and survival in patients with early ovarian
cancer. METHODS AND PATIENTS: Between 1981 and 1990, 125 patients with optimally
debulked Stage I, II, and III ovarian cancer were entered into a prospective
randomized clinical trial of abdominopelvic radiation therapy. Patients were
stratified and randomized to either the control arm, treated with an abdominal
dose of 22.5 Gy in 22 fractions, or the experimental arm of 27.5 Gy in 27
fractions. A pelvic boost dose of 22.5 Gy was used in both arms. There were 43
patients with Stage I tumors, 71 Stage II tumors, and 11 Stage III tumors.
Nineteen patients had grade 1 histology, 77 grade 2, and 29 grade 3. Three
patients had small-volume residual disease (<2 cm) in the pelvis alone and the
remainder had no gross tumor following surgery. Median follow-up was 6.6 years
(range 1.4-9.9). RESULTS: Overall survival (OS) at 5 years was 83% in the low
dose arm and 72% in the high-dose arm (p = 0.3). Disease-free survival (DFS) at 5
years was 74% and 67% in the low-dose and high-dose arms, respectively (p = 0.5).
The difference in OS between the two arms was -11%, with 95% confidence intervals
of -26% (favoring low-dose treatment) to 4% (in favor of high dose). The
difference in DFS was -7% (95% confidence interval, -23 to 9%). Failure in the
pelvis alone predominated (n = 15); six patients had abdominal and pelvic failure
and seven patients failed in the abdomen alone. There were no differences in
patterns of relapse, hematologic toxicity, or late complications between the two
arms. Serious bowel toxicity was seen in three patients: two in the low-dose and
one in the high-dose arm. A Cox proportional hazards model was used to assess the
effect of treatment when adjusting for other prognostic variables. Ascites (p =
0.03, relative risk 2.05) was the only significant covariate in predicting
disease-free survival, but was not prognostic for overall survival. CONCLUSIONS:
There was no difference in survival, tumor control, or toxicity between high-dose
and low-dose abdominopelvic radiation therapy. High-dose abdominopelvic radiation
therapy is unlikely to be associated with an increase in OS of more than 4% or
DFS of more than 9%.
PMID- 9635701
TI - Preoperative radiotherapy and surgery for endometrial carcinoma: prognostic
significance of the sterilization of the specimen.
AB - INTRODUCTION: We report a retrospective study on the analysis of the operative
specimen after preoperative radiotherapy for FIGO (1971) stage I or II
endometrial carcinoma. METHODS AND MATERIALS: From 1976 to 1996, 221 patients
were treated with external radiotherapy (XRT) and/or low-dose-rate brachytherapy
(BT) followed by surgery (S). Patients with cervical involvement (89 patients) or
with high-grade tumors (49 patients) received XRT and BT. Patients stage FIGO Ia
(89 patients) or with low-grade tumors (57 patients) received BT alone. Surgery
was performed 5 to 6 weeks after irradiation. RESULTS: The mean follow-up is 78
months (12-216). The 5-year survival was 90% for FIGO Ia, 80% for FIGO Ib, and
84% for FIGO II (p = 0.51). According to the differentiation, 5-year survival was
87% for grade 1, 84% for grade 2, 84% for grade 3 (p = 0.10). Grade 3
complications were registered in 2% (no grade 4). The tumors were sterilized in
37 patients (17%), sterilized but with dystrophic glands in 34 patients (16%),
only modified and altered in 21 patients (9.5%), with viable cells in 56 patients
(26%). After preoperative radiotherapy, 37/148 specimens were sterilized (25%),
14/74 after brachytherapy and surgery (19%), 23/74 after external radiotherapy
brachytherapy and surgery (31%). According to the response of the specimen, 5
year survival was 87% when the tumor was sterilized, 96% when altered glands were
present, 85% when modified, and 76% if residual tumor with viable cells was
identified (p = 0.043). CONCLUSION: Preoperative radiotherapy followed by surgery
is a safe and effective treatment of FIGO stage I or II endometrial carcinomas.
BT with two uterine tubes seems to be of interest in the contribution of the
treatment of the uterus to sterilize the specimen. The analysis of this new
prognostic factor remains important to select a population with worst prognosis.
PMID- 9635702
TI - Comprehensive irradiation of head and neck cancer using conformal multisegmental
fields: assessment of target coverage and noninvolved tissue sparing.
AB - PURPOSE: Conformal treatment using static multisegmental intensity modulation was
developed for patients requiring comprehensive irradiation for head and neck
cancer. The major aim is sparing major salivary gland function while adequately
treating the targets. To assess the adequacy of the conformal plans regarding
target coverage and dose homogeneity, they were compared with standard
irradiation plans. METHODS AND MATERIALS: Fifteen patients with stage III/IV head
and neck cancer requiring comprehensive, bilateral neck irradiation participated
in this study. CT-based treatment plans included five to six nonopposed fields,
each having two to four in-field segments. Fields and segments were devised using
beam's eye views of the planning target volumes (PTVs), noninvolved organs, and
isodose surfaces, to achieve homogeneous dose distribution that encompassed the
targets and spared major salivary gland tissue. For comparison, standard three
field radiation plans were devised retrospectively for each patient, with the
same CT-derived targets used for the clinical (conformal) plans. Saliva flow
rates from each major salivary gland were measured before and periodically after
treatment. RESULTS: On average, the minimal dose to the primary PTVs in the
conformal plans [95.2% of the prescribed dose, standard deviation (SD) 4%] was
higher than in the standard plans (91%, SD 7%; p = 0.02), and target volumes
receiving <95% or <90% of the prescribed dose were smaller in the conformal plans
(p = 0.004 and 0.02, respectively). Similar advantages of the conformal plans
compared to standard plans were found in ipsilateral jugular nodes PTV coverage.
The reason for underdosing in the standard treatment plans was primarily failure
of electron beams to fully encompass targets. No significant differences were
found in contralateral jugular or posterior neck nodes coverage. The minimal dose
to the retropharyngeal nodes was higher in the standard plans. However, all
conformal plans achieved the planning goal of delivering 50 Gy to these nodes. In
the conformal plans, the magnitude and volumes of high doses in noninvolved
tissue were significantly reduced. The main reasons for hot spots in the standard
plans (whose dose calculations included missing tissue compensators) were
photon/electron match line inhomogeneities, which were avoided in the conformal
plans. The mean doses to all the major salivary glands, notably the contralateral
parotid (receiving on average 32% of the prescribed dose, SD 7%) were
significantly lower in the conformal plans compared with standard radiation
plans. The mean dose to the noninvolved oral cavity tended to be lower in the
conformal plans (p = 0.07). One to 3 months after radiation, on average 60% (SD
49%) of the preradiation saliva flow rate was retained in the contralateral
parotid glands and 10% (SD 16%) was retained in the submandibular/sublingual
glands. CONCLUSIONS: Planning and delivery of comprehensive irradiation for head
and neck cancer using static, multisegmental intensity modulation are feasible.
Target coverage has not been compromised and dose distributions in noninvolved
tissue are favorable compared with standard radiation. Substantial major salivary
gland function can be retained.
PMID- 9635703
TI - Parathyroid carcinoma--the Princess Margaret Hospital experience.
AB - PURPOSE: Carcinoma of the parathyroid gland is a rare disease representing 0.5 to
4% of patients with primary hyperparathyroidism. We reviewed our experience with
this disease, with special emphasis on the role of adjuvant postoperative
radiotherapy. METHODS: A retrospective review was conducted of all cases of
parathyroid carcinoma referred to the Princess Margaret Hospital (PMH) from 1958
1996. Ten patients were identified. Their clinical features, management details,
and treatment outcome are described. RESULTS: There were 5 men and 5 women with a
mean age of 53 years. Of these, 7 patients underwent en bloc resection; among
them, 4 had neck dissection or lymph node sampling. The other 3 patients
underwent only limited surgery to remove the tumor. Seven patients were referred
for consideration of adjuvant radiation treatment. Six patients were given
adjuvant radiation therapy for microscopic residual disease. All patients
tolerated the radiation treatment well, with minimal side effects. The 7 patients
have been followed regularly with no evidence of recurrence and normal serum
calcium. The mean follow-up for the 6 patients who had adjuvant radiotherapy was
62.3 months (range 12 to 156 months). The remaining 3 patients had metastatic
disease and were referred for palliative radiotherapy. CONCLUSIONS: Our results
in a small number of patients suggest local radiation therapy to the tumor bed
may have eliminated the strong predilection for local recurrence of this disease,
as reported by other investigators.
PMID- 9635704
TI - Prognostic significance of DNA content in stage I adenocarcinoma of the lung.
AB - PURPOSE: Up to 30% of lung cancers (Stage I) with the most favorable outcome
recur within 5 years after surgery. This study reviews the pattern of failure
after surgical resection in early lung cancers and determines whether flow
cytometric DNA variables were prognostic indicators for survival, disease-free
survival (DFS), or distant metastasis-free survival (DMFS). METHODS AND
MATERIALS: Pathologic specimens from 45 patients at The University of Texas M. D.
Anderson Cancer Center who underwent surgical resection and mediastinal nodal
dissection for stage I (AJCC) adenocarcinomas of the lung were analyzed by flow
cytometry for DNA content. Survival was calculated by the method of Desu and Lee.
Chi-square and cross tabulation were used in the analysis. RESULTS: The mean age
of the patients was 62 years, and 52.3% were male. All patients were clinical
Stage I (T1-2 N0), Karnofsky performance status > or = 70, and had a weight loss
<10 lbs. Median overall survival (OS) and DFS were 50 months and 33 months,
respectively. OS, DFS, and DMFS at 1, 3 and 5 years were 73%, 57%, and 35%; 63%,
53%, and 45%; and 67%, 56%, and 48%, respectively. Analysis of all 45 patients
revealed 86% of patients developing brain metastasis had an abnormal DNA content
> or = 30%, whereas 4% of patients with brain metastasis had abnormal DNA content
< 30% (p = 0.01). This correlation maintained significance when only pT1/2
lesions were analyzed. There was a significant statistical correlation between
abnormal DNA and 5-year OS, with 74% OS for those with abnormal DNA < 30% vs. 42%
for > or = 30% (p = 0.036). The 5-year DFS for pT1/2 patients was significantly
correlated with abnormal DNA content: 53% for patients with abnormal DNA < 30%
vs. 17% for patients with abnormal DNA > or = 30%, respectively (p = 0.03). Of
those with %S fraction (%S) < 2, 13% failed locally compared to 41% of those with
%S > or = 2. There was a highly significant correlation between DNA index (DNAI)
and aneuploid %S: 68% of patients with a DNAI > or = 1.7 had > or = 2.6 aneuploid
%S, whereas only 13% of patients with DNAI > or = 1.7 had aneuploid %S < 2.6. (p
< 0.001). Grouping the percent of abnormal DNA and overall %S according to low
vs. mixed vs. high values correlated with DFS (p = 0.02). CONCLUSIONS: This study
confirms significant correlation between a high DNA index and a higher frequency
of brain metastasis, as well as worse OS. Although DNA content variables were not
predictive of recurrence at other sites, brain metastasis represents the worst
outcome from distant metastasis. Further studies are needed, as well as
prospective trials, for evaluating adjuvant therapy in patients with adverse DNA
variables following complete surgical resection for early disease. If high-risk
patients could be identified after resection, adjuvant therapy (chemotherapy or
elective brain irradiation) could be administered.
PMID- 9635705
TI - Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using
individual patient data (Oesophageal Cancer Collaborative Group).
AB - PURPOSE: The existing randomized evidence has failed to conclusively demonstrate
the benefit or otherwise of preoperative radiotherapy in treating patients with
potentially resectable esophageal carcinoma. This meta-analysis aimed to assess
whether there is benefit from adding radiotherapy prior to surgery. METHODS AND
MATERIALS: This quantitative meta-analysis included updated individual patient
data from all properly randomized trials (published or unpublished) comprising
1147 patients (971 deaths) from five randomized trials. RESULTS: With a median
follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests
an overall reduction in the risk of death of 11% and an absolute survival benefit
of 3% at 2 years and 4% at 5 years. This result is not conventionally
statistically significant (p = 0.062). No clear differences in the size of the
effect by sex, age, or tumor location were apparent. CONCLUSION: Based on
existing trials, there was no clear evidence that preoperative radiotherapy
improves the survival of patients with potentially resectable esophageal cancer.
These results indicate that if such preoperative radiotherapy regimens do improve
survival, then the effect is likely to be modest with an absolute improvement in
survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients
would be needed to reliably detect such an improvement (15-->20%).
PMID- 9635706
TI - Apoptosis, proliferation, bax, bcl-2 and p53 status prior to and after
preoperative radiochemotherapy for locally advanced rectal cancer.
AB - PURPOSE: To investigate the relationship between apoptotic cell death,
proliferative activity, and the expression of apoptosis regulating proteins in
rectal cancer prior to and after radiochemotherapy. MATERIALS AND METHODS: In 32
patients dispositioned to receive preoperative radiochemotherapy for locally
advanced rectal carcinoma, pretherapy biopsies and the final resected specimen
after radiochemotherapy were available for analyses. Apoptotic cells were
identified and quantified using in situ end labeling (ISEL) technique. The
expression of the bax protein was assessed immunohistochemically. Additionally,
double immunostaining was performed for apoptotic cells and bax expression. The
proliferative activity was determined by immunohistochemical assessment of the
Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2
expression was analyzed immunohistochemically. A clinical-to-pathologic
downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%).
During follow-up, tumor recurrence was observed in six cases. In one case, no
residual tumor was detected after radiochemotherapy. RESULTS: After
radiochemotherapy, the apoptotic index increased significantly in almost every
case examined. In contrast, the proliferative activity was significantly
decreased in resected specimens as compared to biopsies. Bax immunostaining was
detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the
resected specimen, significantly more apoptotic cells that were bax-positive were
found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31
resected specimens, respectively. Tumors that were immunohistochemically negative
for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high
expression level of bax than p53-positive tumors (11/31 [35%]). However, we did
not find any correlation between the (pre- and post-therapeutic) rate of
apoptosis or the level of bax expression and the degree of clinical-to-pathologic
downstaging or the frequency of tumor recurrence. CONCLUSION: Our results
indicate that radiochemotherapy is associated with an increase in bax expression
and also in apoptotic cell death. The observation of higher rates of apoptosis
and bax in p53-negative tumors suggests that p53 might be a possible regulating
factor of apoptosis in rectal cancer.
PMID- 9635707
TI - Acute treatment-related diarrhea during postoperative adjuvant therapy for high
risk rectal carcinoma.
AB - PURPOSE: The combination of pelvic radiotherapy and 5-fluorouracil-based
chemotherapy is associated with an increase in acute gastrointestinal toxicity
during rectal adjuvant therapy, most notably an increased incidence of diarrhea.
Previous randomized, prospective studies have limited their analysis to
presenting rates of severe and life-threatening diarrhea (Grade 3 or greater),
and few data are available detailing the extent of mild to moderate diarrhea. To
provide baseline data for future studies, we conducted a detailed analysis of
diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer.
METHODS AND MATERIALS: In a multiinstitutional clinical trial, 204 eligible
patients with rectal carcinoma that either was deeply invasive (T3-T4) or
involved regional lymph nodes were randomized to receive either postoperative
pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5
fluorouracil-based chemotherapy. Toxicity was assessed prospectively. RESULTS:
For the 99 eligible patients who received pelvic radiotherapy alone, rates of
Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%,
respectively. For the 96 eligible patients who received radiotherapy and 5
fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34,
23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant
rectal therapy were manifested across all toxicity levels for patients receiving
chemotherapy and pelvic radiotherapy. Of primary clinical importance is the
substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22
vs. 4%,p = 0.001) Additionally, increased rates of any diarrhea and also severe
or life-threatening diarrhea were observed in patients who had a low anterior
resection compared with those who had an abdominoperineal resection (p < 0.001
and p = 0.006, respectively). CONCLUSION: These results will be of value as a
baseline for investigators who want to use treatment toxicity as an end point in
cancer control or cancer therapy trials utilizing similar treatment techniques.
Patients receiving 5-fluorouracil and pelvic radiotherapy compared with patients
receiving pelvic radiotherapy alone and patients with a prior history of a low
anterior resection compared with patients who had a prior history of an
abdominoperineal resection experienced increased rates of Grades 1 through 4
acute treatment-related diarrhea, and the most important increase occurred as
Grade 3 toxicity.
PMID- 9635708
TI - A close or positive margin after mastectomy is not an indication for chest wall
irradiation except in women aged fifty or younger.
AB - INTRODUCTION: Indications for postmastectomy radiation include primary tumor size
> or = 5 cm and/or > or = 4 positive axillary nodes. In clinical practice,
patients with a close or positive margin after mastectomy are also often treated
with postmastectomy radiation. However, there is little data regarding the risk
of a chest wall recurrence in patients with close or positive margins who
otherwise would be considered low risk (tumor size <5 cm and/or 0-3 positive
nodes). To address this issue, we assessed the risk of a chest wall recurrence in
women with Stage I-II breast cancer who underwent mastectomy and were found to
have primary tumor size <5 cm and 0-3 positive nodes with a close or positive
deep margin. METHODS AND MATERIALS: The pathologic reports from 789 patients
treated by mastectomy between 1985 and 1994 at our institution were
retrospectively reviewed. Of these, 136 (17%) had tumor within 1 cm of the deep
resection margin. The study population consists of 34 of these patients with
close or positive margins whose primary tumor size was <5 cm with 0-3 positive
axillary nodes and who received no postoperative radiation. The median age was 43
years (range 29-76). Of these, 44% had T1 tumors and 56% T2 tumors. Pathologic
axillary nodal status was negative in 65% and positive in 35%. The median number
of positive nodes was 1. The deep margin was positive in 2 patients, < or = 2 mm
in 17 patients, 2.1-4 mm in 7 patients and 4.1-6 mm in 8 patients. Of the 34
patients, 67% received adjuvant chemotherapy +/- tamoxifen and 21% received
tamoxifen alone. The median follow-up was 59 months (range 7-143). RESULTS: There
were 5 chest wall recurrences at a median interval of 26 months (range 7-127).
One was an isolated first failure, one occurred concurrent with an axillary
recurrence, and three were associated with distant metastases. The 5- and 8-year
cumulative incidences of a chest wall recurrence were 9% and 18%. Patient age
correlated with the cumulative incidence of chest wall recurrence at 8 years; age
< or = 50 years had a rate of 28% vs. 0% for age >50 (p = 0.04). There was no
correlation with chest wall failure and number of positive nodes, ER status,
lymphovascular invasion, location of primary, grade, family history, or type of
tumor close to the margin. Of 5 chest wall failures, 4 were in patients who had
received adjuvant systemic chemotherapy +/- tamoxifen. Chest wall failures
occurred in 1 patient with a positive deep margin, 3 patients with margins within
2 mm, and 1 patient with a margin of 5 mm. The estimated cumulative incidence
probability of chest wall recurrence at 8 years by margin proximity was 24% < or
= 2 mm vs. 7% 2.1-6 mm (p = 0.36), and by clinical size 24% for T2 tumors vs. 7%
for T1 (p = 0.98). CONCLUSIONS: A close or positive margin is uncommon (< or =
5%) after mastectomy in patients with tumor size <5 cm and 0-3 positive axillary
nodes but, when present, it appears to be in a younger patient population. The
subgroup of patients aged 50 or younger with clinical T1-T2 tumor size and 0-3
positive nodes who have a close (< or = 5 mm) or positive mastectomy margin are
at high risk (28% at 8 years) for chest wall recurrence regardless of adjuvant
systemic therapy and, therefore, should be considered for postmastectomy
radiation.
PMID- 9635709
TI - Diagnostic thoracic-computed tomography in radiotherapy for loco-regional
recurrent breast carcinoma.
AB - PURPOSE: This study was initiated to evaluate whether pretreatment diagnostic
thoracic CT scan was useful for patients with loco-regional recurrent breast
carcinoma, and to assess its impact on the design of radiotherapeutic treatment.
METHODS AND MATERIALS: Between March 1991 and January 1997, 44 patients underwent
thoracic CT examination with contrast material before the consideration of
radiotherapy for their isolated loco-regional recurrent breast carcinoma. The CT
radiographs were prospectively reviewed for additional findings clinically
undetected by prior physical examination and plain-chest radiograph. The changes
made in treatment design and dosage of radiation as a result of CT findings were
recorded for analysis. The correlation between prognostic indicators and the CT
findings was also studied. RESULTS: Twenty-two of 44 (50%) patients were found to
have additional abnormalities detected only after thoracic CT examinations were
performed. The strategy of radiation therapy was altered in 17 of 22 (77%)
patients as a result. Patients with shorter disease-free interval (p = 0.08) and
multiple sites of recurrence (p = 0.05) tended to have greater numbers of
findings on CT scan previously unsuspected. Thus, CT scan is a valuable guide to
treating loco-regional recurrent disease. CONCLUSION: Pretreatment diagnostic
thoracic CT scan offers essential information that can alter treatment planning
and thus optimize treatment strategy for a large proportion of patients with
clinically isolated loco-regional recurrent breast carcinoma. In this population
of patients we recommend that thoracic CT examination be considered before the
initiation of radiation therapy.
PMID- 9635710
TI - Primary central nervous system lymphoma: age and performance status are more
important than treatment modality.
AB - PURPOSE: To assess prognostic factors and treatment modalities of patients with
primary central nervous system lymphoma (PCNSL) in terms of response rates,
patterns of failure and overall survival. METHODS AND MATERIALS: Sixty-two
patients presenting with PCNSL between 1982 and 1994 at Peter MacCallum Cancer
Institute with no evidence of human immunodeficiency virus infection were
included in the study. Their median age was 60 years; World Health Organisation
(WHO) performance status was > or = 2 in 85%. All patients were planned to
receive whole brain irradiation; 7 also received spinal irradiation. The median
planned dose to the target volume was 50.4 Gy. Twenty patients were planned to
receive chemotherapy as well. Patients were followed up to June 20, 1995, giving
a median follow-up for 14 surviving patients of 5.4 years, range 0.3 to 10.2
years. RESULTS: The clinical response rate to treatment was 77% [95% confidence
interval (CI) 65 to 87%]. The estimated median overall survival was 20.6 months
(CI 12.4 to 33.4 months). On univariate analysis male gender, age <60 years, WHO
performance status < or = 1, treatment to the target volume > or = 45 Gy, and
treatment with additional chemotherapy, were associated with a significantly
better overall survival (p < 0.05). On multivariate analysis only age and
performance status remained significant prognostic variables. Relapse involved
the central nervous system or cerebrospinal fluid (CSF) in all patients with
known sites of relapse except three who had ocular relapse only. There was a low
incidence of relapse in the initial brain site (23% of known cases) and a high
incidence (50%) of CSF/spinal cord relapse. Of 48 deaths, 15 were related to
initial or subsequent treatment. CONCLUSIONS: Patient outcome is strongly
influenced by age and performance status. Studies suggesting better survival for
patients treated with chemoradiation may reflect patient selection rather than
treatment variables. Optimal management remains to be defined. The high
CSF/spinal relapse rate deserves particular attention.
PMID- 9635711
TI - Determination of the inferior border of the thecal sac using magnetic resonance
imaging: implications on radiation therapy treatment planning.
AB - PURPOSE: To determine whether the traditional teaching of placing the caudal
border of the spinal field at the S2-S3 interspace in children receiving
craniospinal irradiation (CSI) is appropriate. METHODS AND MATERIALS: Twenty
three children had magnetic resonance imaging (MRI) of the spine with gadolinium
prior to craniospinal irradiation at one institution. Thecal sac termination
using MRI was determined by drawing a perpendicular line from the point of
convergence of dural margins to the corresponding vertebral body. RESULTS:
Location of thecal sac termination varied from mid-S1 to low S3 vertebral body,
with the most frequent site at the upper S2 vertebral level. Only 2 of 23 (8.7%)
children had thecal sac terminations below the S2-S3 interspace. For the nine
patients with neuraxis disease, none had thecal sac terminations below the S2-S3
interspace. In seven of the nine patients who had neuraxis seeding at initial
presentation, MRI of the spine after CSI was performed and showed that thecal sac
termination was lower after radiation therapy in two children, higher in one, and
the same in four. CONCLUSIONS: In 2 of 23 children (8.7%), placement of the
inferior border at the bottom of the S2 vertebral body would have missed the
entire thecal sac. Treatment to the entire neuraxis with adequate coverage of
distal spinal theca can be achieved by using MRI. Individualized spinal fields
using the MRI may help minimize radiation scatter to the gonads while adequately
covering the target volume.
PMID- 9635712
TI - Defining the superior border of posterior fossa radiation treatment fields.
AB - PURPOSE: Lateral posterior fossa treatment fields are usually defined on
traditional simulation films based on bony landmarks. The superior field border,
intended to include the apex of the tentorium cerebelli, is frequently difficult
to define. While sagittal magnetic resonance imaging (MRI) images or three
dimensional treatment planning tools are good means to locate the tentorial apex,
these are not always available. We herein describe a method for locating the
tentorial apex based on bony landmarks. METHODS AND MATERIALS: Midsagittal
magnetic resonance images of 53 patients were reviewed. Using a Cartesian grid,
the geometric relationship between the tentorial apex and several bony landmarks
was assessed. Two lines were defined: the first connected the posterior clinoid
and the internal occipital protuberance (AB). The second was perpendicular to the
first, included the tentorial apex, and extended from the base of the skull
inferiorly to the "crown" of the skull superiorly (DE). Relationships between
measurements were made using linear regression and least square fits. RESULTS:
Line DE was within 5 mm of the perpendicular bisector of line AB in 83% (44/53)
of patients. The tentorial apex was located within 10 mm of the midpoint of DE in
91% (48/53) of patients. CONCLUSION: In the majority of patients, the location of
the tentorial apex can be estimated based on bony landmarks, to within
approximately 10 mm. The technique described is a useful means of estimating the
location of the tentorial apex in patients where sagittal MRI imaging or three
dimensional treatment planning tools are not available.
PMID- 9635714
TI - Augmented therapy of extensive Hodgkin's disease: radiation to known disease or
prolongation of induction chemotherapy did not improve survival--results of a
Cancer and Leukemia Group B study.
AB - PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's
disease was undertaken to assess the potential benefit of augmented therapy (12
months chemotherapy or radiation to known disease) compared to standard 6 months
chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were
randomized to four treatment regimens consisting of six cycles of CCNU,
vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles
of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy,
and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all
patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated
areas of known disease occurred in only 6% of responding patients. There was,
however, no statistical difference in response frequency, disease-free survival,
or overall survival among the four regimens. Elderly patients responded less
frequently. CONCLUSION: While radiotherapy provided control of local (known)
disease, no impact on overall survival was apparent. Likewise, doubling the
duration of chemotherapy did not improve response or survival. Augmentation of
therapy with either radiotherapy or more chemotherapy in this study was of no
benefit compared to the standard 6 months of treatment.
PMID- 9635713
TI - Disposition and tissue distribution of boron after infusion of borocaptate sodium
in patients with malignant brain tumors.
AB - PURPOSE: In the frame of the Czech boron neutron capture therapy (BNCT) project,
a clinical Phase I study of borocaptate sodium [Na2B12H11SH (BSH)] as the boron
10 delivery agent was performed to obtain data on disposition and tissue
distribution of boron after an infusion of this compound, as well as to establish
an optimal protocol for BNCT of malignant cerebral tumors. METHODS AND MATERIALS:
The kinetics of boron disposition after an infusion of borocaptate sodium (25
mg/kg body wt over the period of 1 h) was studied in a group of 10 patients with
astrocytoma or glioblastoma of cerebral hemispheres using a modification of the
Soloway-Messer colorimetric method. The boron content of tissues (tumor, healthy
brain, dura mater, muscle, skin, and cranial bone) removed during the operation
performed with latencies varying between 3 and 18 h was investigated by atomic
emission spectrometry. RESULTS: Compartmental analysis of boron blood
concentrations has shown that in the majority of patients (four males and three
females), the concentration decline can be adequately described by a two
compartment pharmacokinetic model (i.e., by a biexponential relationship). The
calculated half-lives of the initial (fast) phase of the concentration decline
varied between 0.85 and 3.65 h, whereas the half-life values for the terminal
(slow) phase ranged between 22.2 and 111.8 h. However, in the remaining three
patients (all females), the goodness of fit of the boron concentration data was
significantly better when a pharmacokinetic model with three compartments was
assumed. In these patients, therefore, an additional ultrafast phase with a half
life varying between 17 and 37 min was detected in the beginning of the boron
blood concentration decline. On the other hand, in one of these patients, the
half-life of the terminal phase was found to be 415 h (i.e., more than 17 days).
Such a long persistence in the body is explained by the very high value of the
total distribution volume, indicating extensive binding of BSH in peripheral
tissues. Another reason may be enterohepatic recycling of BSH. CONCLUSION: Tumor
to-blood ratios higher than 1.5, which are necessary for an effective outcome of
BNCT, can be obtained only if the time interval elapsing between the onset of
surgery and termination of BSH infusion is at least 12 h.
PMID- 9635715
TI - Outcomes of high-dose unilateral kidney irradiation in patients with gastric
lymphoma.
AB - PURPOSE: To review the long-term clinical effects of unilateral kidney
irradiation on overall renal function and blood pressure in patients with gastric
lymphoma. METHODS AND MATERIALS: In the study were 27 patients with Stage I or II
gastric lymphoma who had undergone irradiation of at least 24 Gy to > or = 1/3 of
the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age
of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II
disease. In 13 patients the whole kidney had been irradiated, and 14 had had
partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients
received combined chemotherapy with various drugs: all patients received
corticosteroids, and five received cis-platinum. Their follow-up ranged between
0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on
blood pressure, renal function as assessed by blood urea and creatinine, and
kidney shrinkage as seen by serial computed tomography scanning were collected on
all patients. RESULTS: Three patients had persistent, mild elevations of urea and
creatinine levels, which did not require special treatment. All three also
received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients.
In 19 patients the craniocaudal measurement of the kidney shrank by > or = 1.6
cm. Shrinkage in other dimensions was also evident. The degree of atrophy was
related to the volume of kidney irradiated. Only two patients developed
hypertension, both at a low level of 150/90; one patient had had 40 Gy to the
whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated
urea or creatinine. CONCLUSIONS: Notwithstanding the shrinkage to the irradiated
part of the kidney, the treatment did not lead to clinically significant
hypertension or renal dysfunction. The administration of cis-platinum to patients
with gastric lymphoma that requires kidney irradiation should be further
evaluated.
PMID- 9635716
TI - Interstitial pneumonitis in acute leukemia patients submitted to T-depleted
matched and mismatched bone marrow transplantation.
AB - PURPOSE: To identify factors that could contribute to interstitial pneumonitis
(IP), which remains one of the major causes of morbidity and mortality after both
matched and mismatched bone marrow transplantation (BMT). METHODS AND PATIENTS:
Ninety acute leukemia patients received an allogeneic T-depleted matched (n = 54)
or mismatched (n = 36) BMT. They were preconditioned with total body irradiation
(TBI), thiotepa, rabbit anti-thymocyte globulin, and cyclophosphamide. The TBI
scheme was hyperfractionated in matched, and a single dose in mismatched
patients. The dose to the lungs was reduced in both groups. RESULTS: Five of the
54 matched patients developed IP. All cases were fatal. There were 16 cases of
IP, 13 fatal, in the mismatched group. The probability of developing IP was 11.3
+/- 4.9% and 48.6 +/- 9.0%, respectively. The between-group difference was
statistically significant (p < 0.0001). The type of transplant and the TBI scheme
were the most important parameters for IP development in univariate analysis,
whereas acute graft-versus-host disease, disease stage and sex were
nonsignificant. Median follow-up was 342 days (range 17-2900). CONCLUSIONS: The
low incidence of IP in matched patients and the lack of idiopathic cases are
evidence for the validity of the TBI schedule. In contrast, the incidence in
mismatched patients remains too high; therefore, new strategies should be studied
in an attempt to lower it.
PMID- 9635717
TI - Cataracts after total body irradiation and bone marrow transplantation in
patients with acute leukemia in complete remission: a study of the European Group
for Blood and Marrow Transplantation.
AB - PURPOSE: Advances in bone marrow transplantation (BMT) have consistently improved
long-term survival. Therefore, evaluation of late complications such as cataracts
is of paramount importance. METHODS AND MATERIALS: We analyzed data of 2149
patients from the EBMT registry. A cohort of 1063 patients were evaluable for
survival and ophthalmologic status after transplant for acute leukemia (AL) in
first or second complete remission. Conditioning therapy included either single
dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in
different dose rates (low: LDR < or = 0.04 Gy/min; high: HDR > 0.04 Gy/min).
RESULTS: The overall 10-year estimated cataract incidence (ECI) was 50%. It was
60% in the STBI group, 43% in the FTBI group < or = 6 fractions, and 7% in the
FTBI group > 6 fractions (p < 10(-4)). It was significantly lower (30%) in the
LDR than in the HDR groups (59%;p < 10(-4)). Patients receiving heparin for veno
occlusive disease prophylaxis had fewer cataracts than those who did not (10-year
ECI: 33% vs. 53%, respectively;p = 0.04). The 10-year ECI was 65% in the
allogeneic vs. 46% in the autologous BMT patients (p = 0.0018). Factors
independently associated with an increased risk of cataract were an older age (>
23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid
administration (> 100 days). The use of FTBI was associated with a decreased risk
of cataract. Heparin administration was a protective factor in patients receiving
STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery
were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease
(cGvHD), and absence of heparin administration. Among the patients who required
cataract surgery (111 out of 257), secondary posterior capsular opacification was
observed in 15.7%. CONCLUSION: High dose rate and STBI are the main risk factors
for cataract development and the need for surgery, and the administration of
heparin has a protective role in cataractogenesis.
PMID- 9635718
TI - Change in E-cadherin expression after X-ray irradiation of a human cancer cell
line in vitro and in vivo.
AB - PURPOSE: To investigate changes in E-cadherin expression after X-ray irradiation
of a human cancer cell line in vitro and in vivo. METHODS AND MATERIALS: E
cadherin expression on a human squamous cell carcinoma of the thyroid gland (T
SCC cell), which was established in our laboratory, at 24 h after graded single
doses of irradiation and at 7 successive times after 10-Gy irradiation were
investigated in vitro by immunoblot analysis with the monoclonal antibody to
human E-cadherin. The changes in E-cadherin expression caused by irradiation of T
SCC tumors that were transplanted into athymic nude mice were also determined in
vivo by immunohistochemical staining and immunoblot analysis in a similar fashion
to that in vitro. RESULTS: In vitro studies revealed that E-cadherin expression
had increased significantly on T-SCC cells at 24 h after irradiation with doses
of 2 to 10 Gy and that, in a time-course analysis, the expression had increased
significantly at 3 to 72 h after irradiation compared with an unirradiated
control cell, although it was not observed at 1 h after irradiation. In in vivo
studies, a significant increase in E-cadherin expression was observed at 24 h
after irradiation with 5 and 10 Gy by immunohistochemical staining and time
course studies demonstrated that E-cadherin increased temporarily at 12 to 24 h
after 10-Gy irradiation; however, immunoblot analysis did not show alteration of
E-cadherin expression by irradiation. CONCLUSION: X-ray irradiation upregulated E
cadherin expression on T-SCC cells in vitro and in vivo.
PMID- 9635719
TI - The effect of activation of wild-type p53 function on fluoropyrimidine-mediated
radiosensitization.
AB - PURPOSE: We have hypothesized that fluoropyrimidine-mediated (FdUrd)
radiosensitization occurs in cells that inappropriately enter S phase in the
presence of drug, resulting in defective repair of radiation-induced DNA damage
(14). This model would predict that prevention of entry into S phase would
abrogate sensitization produced by FdUrd. We wished to test this prediction by
blocking S phase entry of HT29 human colon cancer cells. METHODS: We used HT29
cells that had been transduced with a murine temperature-sensitive p53 (ts29G)
and, as a control, HT29 cells transduced with a neomycin plasmid (HT29neo). The
murine temperature-sensitive p53 demonstrates wild-type p53 function when cells
are incubated at the permissive temperature (32 degrees C) and mutant p53
function at the nonpermissive temperature (38 degrees C). We determined the
effect of wt p53 function on FdUrd-mediated radiosensitization and cell cycle
progression. RESULTS: Incubation of ts29G cells at the permissive temperature (32
degrees C) activated p21 and blocked entry of cells into S phase. Whereas FdUrd
greatly increased the radiosensitivity of HT29neo cells and ts29G cells incubated
at 38 degrees C, FdUrd had no effect on the radiation sensitivity of ts29G cells
incubated at the permissive temperature (32 degrees C). CONCLUSIONS: These
findings are consistent with our hypothesis that FdUrd-mediated
radiosensitization requires progression into S phase. It is possible that the
heterogeneity of clinical responses seen after combined therapy with
fluoropyrimidines and radiation is explained, in part, by differences among tumor
cells in the control of S phase progression.
PMID- 9635720
TI - Multivariate logistic analysis of dose-effect relationship and latency of
radiomyelopathy after hyperfractionated and conventionally fractionated
radiotherapy in animal experiments.
AB - PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is
enhanced by using hyperfractionated radiotherapy compared to a conventional
schedule. Higher tolerable doses to the spinal cord would allow dose escalation
to the tumor and thus possibly lead to higher cure rates, especially in tumors
with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276
healthy rats was irradiated over 6 weeks hyperfractionally with single doses
ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions)
and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy
(30 fractions). The rats were examined neurologically and sacrificed when
paralysis of the hind legs occurred. After fixation, spinal cord was removed and
examined histologically. Dose-effect relationship and latency from the beginning
of radiotherapy to the onset of paralysis were computed and analyzed using a
multivariate logistic regression model. RESULTS: The model fitted the observed
data excellently. There were highly significant effects both for the dose level
and for the treatment regimen. Latency analysis showed earlier and more intense
acute side effects after hyperfractionation but radiomyelopathy occurred markedly
later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as
predicted by radiobiologists could be confirmed in our experiments. Thus, it
seems possible to escalate tumor doses using hyperfractionation without enhanced
risk to spinal cord but with higher probability of tumor cure.
PMID- 9635721
TI - A realistic closed-form radiobiological model of clinical tumor-control data
incorporating intertumor heterogeneity.
AB - PURPOSE: To investigate the role of intertumor heterogeneity in clinical tumor
control datasets and the relationship to in vitro measurements of tumor biopsy
samples. Specifically, to develop a modified linear-quadratic (LQ) model
incorporating such heterogeneity that it is practical to fit to clinical tumor
control datasets. METHODS AND MATERIALS: We developed a modified version of the
linear-quadratic (LQ) model for tumor control, incorporating a (lagged) time
factor to allow for tumor cell repopulation. We explicitly took into account the
interpatient heterogeneity in clonogen number, radiosensitivity, and repopulation
rate. Using this model, we could generate realistic TCP curves using parameter
estimates consistent with those reported from in vitro studies, subject to the
inclusion of a radiosensitivity (or dose)-modifying factor. We then demonstrated
that the model was dominated by the heterogeneity in alpha (tumor
radiosensitivity) and derived an approximate simplified model incorporating this
heterogeneity. This simplified model is expressible in a compact closed form,
which it is practical to fit to clinical datasets. Using two previously analysed
datasets, we fit the model using direct maximum-likelihood techniques and
obtained parameter estimates that were, again, consistent with the experimental
data on the radiosensitivity of primary human tumor cells. This heterogeneity
model includes the same number of adjustable parameters as the standard LQ model.
RESULTS: The modified model provides parameter estimates that can easily be
reconciled with the in vitro measurements. The simplified (approximate) form of
the heterogeneity model is a compact, closed-form probit function that can
readily be fitted to clinical series by conventional maximum-likelihood
methodology. This heterogeneity model provides a slightly better fit to the
datasets than the conventional LQ model, with the same numbers of fitted
parameters. The parameter estimates of the clinically important time factors and
lag periods are very similar to those obtained from the conventional LQ model,
but with slightly narrower confidence intervals, reflecting the better fit to the
clinical data. DISCUSSION: We have demonstrated, as have others, the importance
of intertumor heterogeneity in the response of patient populations to
radiotherapy. With the possible inclusion of a radiosensitivity-modifying factor
(in vitro/in vivo) of around 1.7, the in vivo data can be made consistent with
the in vitro SF2 and Tpot data. Fitting two previously analyzed multicenter
datasets indicated that previous analyses based on conventional LQ models gave
results for clinically important time factors and lags periods that were not
significantly biased by the failure to include intertumor heterogeneity, with
slightly narrower confidence intervals, reflecting the better fit to the clinical
data. The simple closed-form model we have developed allows direct estimation of
the heterogeneity in radiosensitivity within clinical series, and should prove
useful in the analysis of other clinical series.
PMID- 9635722
TI - Review of eye plaque dosimetry based on AAPM Task Group 43 recommendations.
American Association of Physicists in Medicine.
AB - PURPOSE: AAPM Task Group 43 recently revised the dosimetry recommendations for
125I seeds. We reviewed these guidelines and studied the effects of the
recommendations on the prescription absorbed dose for patients who have undergone
eye plaque therapy in our clinic. METHODS AND MATERIALS: 95 consecutive patients
were chosen for this study. Absorbed doses at various points of clinical interest
were computed based on conventional dose calculation algorithm (3, 4, 7) and TG
43 recommendations. For three representative plaques chosen, the seeds are
approximated by isotropic point and line sources, respectively, and absorbed
doses were calculated at all points on the central axis of the plaque. RESULTS:
For apical heights shorter than 5 mm, treatment plans using model 6711 seeds
delivered 10-13% lower absorbed doses than that calculated previously. For
lesions with apical heights 5 mm or larger, the absorbed dose was 6-12% lower
than prescribed. Calculations for model 6702 seeds indicated that TG-43
recommendations would produce 0-6% lower absorbed doses. Point doses calculated
along the central axis of the plaque and isodose distributions at various levels
showed that point source approximation of the seeds was clinically acceptable.
CONCLUSIONS: TG-43 recommendations, if implemented, would result in lower
absorbed doses unless the dose prescription is modified. The clinicians need to
be aware of the dosimetric implications of these recommendations. The seeds may
be approximated by isotropic point sources.
PMID- 9635723
TI - Impact of beam energy and field margin on penumbra at lung tumor-lung parenchyma
interfaces.
AB - PURPOSE: To determine the characteristics of the penumbra in the region of the
lung tumor-lung parenchyma interfaces for various radiation beam energies and
various field margins. METHODS AND MATERIALS: A phantom simulating the thoracic
cavity with a tumor arising within the lung parenchyma was irradiated with
opposed 6-, 10-, and 18-MV photon beams. Beam profiles were obtained at the
tumor's surface and midplane using radiographic film. The field edge varied from
0.0 to 3.5 cm from the gross tumor volume. The effective penumbra (distance from
80 to 20% dose) and beam fringe (distance from 90 to 50% dose) were measured.
Clinically acceptable beam profiles were defined as those in which no point of
the planning target volume (gross tumor volume plus a 1-cm margin) received less
than 95% of the central tumor dose. RESULTS: Mean effective penumbra and beam
fringe were found to differ in a statistically significant manner with respect to
energy, but not with distance from field edge to gross tumor volume. With the
field edge < or = 1.5 cm from the gross tumor volume, no energy provided an
acceptable dose distribution, as defined above. With the field edge 2 cm from the
gross tumor volume, 6 and 10 MV provided acceptable dose distributions, but 18 MV
did not. With the field edge > or = 2.5 cm from the gross tumor volume, all
energies provided acceptable dose distributions. CONCLUSION: For irradiation of
lung carcinomas in which the planning target volume includes a margin of normal
lung tissue, 6- and 10-MV opposed beams yield a superior dose distribution with
respect to penumbra at the tumor's surface and midplane, with the field edge
placed 2 cm from the gross tumor volume. To achieve an equivalent distribution
with 18-MV photons, a distance of 2.5 cm from field edge to the gross tumor
volume is necessary, leading to an increase in normal lung tissue irradiated.
PMID- 9635724
TI - The use of adaptive radiation therapy to reduce setup error: a prospective
clinical study.
AB - PURPOSE: Adaptive Radiation Therapy (ART) is a feedback treatment process that
optimizes a patient's treatment according to the patient specific information
measured during the course of treatment. Utilizing an electronic portal imaging
device (EPID) and a computer-controlled multileaf collimator (MLC), the ART
process is currently being implemented in our clinic to improve the treatment
accuracy by compensating for the treatment setup error. A prospective study was
conducted to evaluate the feasibility and efficacy of the ART process for
clinical use. METHODS AND MATERIALS: The prospective study included 20 patients
who underwent conventional radiotherapy on a linear accelerator equipped with an
EPID and a MLC. No specific changes were made in the routine clinical procedures
except daily portal images were obtained for each treatment field. Two
dimensional setup error for each treatment field was then measured offline using
a software tool. The measured setup errors from initial treatment days were used
to predict the systematic and random setup errors for each treatment field. An
adjustment decision was made if the predicted systematic error was larger than or
equal to 2 mm. Furthermore, the treatment field was extended if the predicted
random setup error could not be effectively compensated by the predefined
treatment setup margin. Instead of the conventional approach of patient
repositioning, setup adjustment was implemented by reshaping the MLC field. The
entire process from measuring setup error to reshaping the MLC field was
performed offline through a computer network. After completion of a patient's
treatment, the systematic and random setup errors after adjustment were compared
with those predicted prior to the adjustment. The accuracy of the adjustment, and
the reliability and stability of the process were analyzed. RESULTS: Treatment
fields of 13 patients were modified to correct for systematic errors. The mean
systematic error was 4 mm with a range of 2 to 7 mm before adjustment. It was
reduced to 0.5 mm with a range of 0.2 to 1.4 mm after adjustment. There was no
significant difference in random setup errors before and after adjustment. The
ART process was found to be stable, as more than 95% of patient specific setup
margins were predictable within 1 mm using the first four to nine fractions of
treatment, confirming the feasibility of treatment plan reoptimization with the
ART process. CONCLUSIONS: The prospective study demonstrates that the ART process
can be effectively implemented in routine clinical practice to improve treatment
accuracy. This process is also ready to be further extended to reoptimize the
treatment plan by incorporating the predicted patient specific setup variation.
PMID- 9635725
TI - Use of a simulator with CT option in radiotherapy of macular degeneration.
AB - PURPOSE: To assess the accuracy of a conventional simulation procedure in
radiotherapy of age-related macular degeneration. METHODS AND MATERIALS: A
computed tomographic (CT) extension attached to the treatment simulator was used
to acquire CT images immediately after conventional simulation in 18 patients
referred for treatment of age-related macular degeneration. Analysis was
performed on 16 one-sided treatment cases for whom images were obtained. Error
was estimated by the displacement between the observed treatment isocenter and
the intended isocenter based on reconstructed eye geometry. RESULTS: Based on
single slice measurements, the mean error amplitude was 2.3 mm (range 0.2-5.6).
Based on three-dimensional eye globe reconstruction, the mean error amplitude was
2.8 mm (range 0.8-5.3). An incidental finding previously unreported was the lower
image quality at the center of the simulator-CT image acquisition field.
CONCLUSIONS: Small but significant errors from conventional simulation were
noted. The integrated simulation-CT procedure may help correct the errors to
improve the accuracy of simulation setup. The lower image quality at the center
of image acquisition field requires adaptation of the simulation-CT procedure.
PMID- 9635726
TI - Regarding dose prescription for radiotherapy in the lung: Klein et al. IJROBP
37:1163-1170; 1997.
PMID- 9635727
TI - Making movies of molecular motions.
PMID- 9635728
TI - Molecular dynamics simulations of ion channels: how far have we gone and where
are we heading?
PMID- 9635729
TI - Cells use the singular properties of different channels to produce unique
electrical songs.
PMID- 9635730
TI - The pH-induced release of iron from transferrin investigated with a continuum
electrostatic model.
AB - A reduction in pH induces the release of iron from transferrin in a process that
involves a conformational change in the protein from a closed to an open form.
Experimental evidence suggests that there must be changes in the protonation
states of certain, as yet not clearly identified, residues in the protein
accompanying this conformational change. Such changes in protonation states of
residues and the consequent changes in electrostatic interactions are assumed to
play a large part in the mechanism of release of iron from transferrin. Using the
x-ray crystal structures of human ferri- and apo-lactoferrin, we calculated the
pKa values of the titratable residues in both the closed (iron-loaded) and open
(iron-free) conformations with a continuum electrostatic model. With the
knowledge of a residue's pKa value, its most probable protonation state at any
specified pH may be determined. The preliminary results presented here are in
good agreement with the experimental observation that the binding of ferric iron
and the synergistic anion bicarbonate/carbonate results in the release of
approximately three H+ ions. It is suggested that the release of these three H+
ions may be accounted for, in most part, by the deprotonation of the bicarbonate
and residues Tyr-92, Lys-243, Lys-282, and Lys-285 together with the protonation
of residues Asp-217 and Lys-277.
PMID- 9635731
TI - Low-resolution structures of proteins in solution retrieved from X-ray scattering
with a genetic algorithm.
AB - Small-angle x-ray solution scattering (SAXS) is analyzed with a new method to
retrieve convergent model structures that fit the scattering profiles. An
arbitrary hexagonal packing of several hundred beads containing the problem
object is defined. Instead of attempting to compute the Debye formula for all of
the possible mass distributions, a genetic algorithm is employed that efficiently
searches the configurational space and evolves best-fit bead models. Models from
different runs of the algorithm have similar or identical structures. The
modeling resolution is increased by reducing the bead radius together with the
search space in successive cycles of refinement. The method has been tested with
protein SAXS (0.001 < S < 0.06 A(-1)) calculated from x-ray crystal structures,
adding noise to the profiles. The models obtained closely approach the volumes
and radii of gyration of the known structures, and faithfully reproduce the
dimensions and shape of each of them. This includes finding the active site
cavity of lysozyme, the bilobed structure of gamma-crystallin, two domains
connected by a stalk in betab2-crystallin, and the horseshoe shape of pancreatic
ribonuclease inhibitor. The low-resolution solution structure of lysozyme has
been directly modeled from its experimental SAXS profile (0.003 < S < 0.03 A(
1)). The model describes lysozyme size and shape to the resolution of the
measurement. The method may be applied to other proteins, to the analysis of
domain movements, to the comparison of solution and crystal structures, as well
as to large macromolecular assemblies.
PMID- 9635732
TI - Periodic orbits: a new language for neuronal dynamics.
AB - A new nonlinear dynamical analysis is applied to complex behavior from neuronal
systems. The conceptual foundation of this analysis is the abstraction of
observed neuronal activities into a dynamical landscape characterized by a
hierarchy of "unstable periodic orbits" (UPOs). UPOs are rigorously identified in
data sets representative of three different levels of organization in mammalian
brain. An analysis based on UPOs affords a novel alternative method of decoding,
predicting, and controlling these neuronal systems.
PMID- 9635733
TI - A molecular dynamics study of the pores formed by Escherichia coli OmpF porin in
a fully hydrated palmitoyloleoylphosphatidylcholine bilayer.
AB - In this paper we study the properties of pores formed by OmpF porin from
Escherichia coli, based on a molecular dynamics simulation of the OmpF trimer,
318 palmitoyl-oleoyl-phosphatidylethanolamine lipids, 27 Na+ ions, and 12,992
water molecules. After equilibration and a nanosecond production run, the OmpF
trimer exhibits a C-alpha root mean square deviation from the crystal structure
of 0.23 nm and a stable secondary structure. No evidence is found for large-scale
motions of the L3 loop. We investigate the pore dimensions, conductance, and the
properties of water inside the pore. This water forms a complicated pattern, even
when averaged over 1 ns of simulation time. Around the pore constriction zone the
water dipoles are highly structured in the plane of the membrane, oriented by the
strong transversal electric field. In addition, there is a net orientation along
the pore axis pointing from the extracellular to the intracellular side of the
bilayer. The diffusion coefficients of water inside the pore are greatly reduced
compared to bulk. We compare our results to results from model pores (Breed et
al., 1996. Biophys. J. 70:1 643-1 661; Sansom et al. 1997. Biophys. J. 73:2404
241 5) and discuss implications for further theoretical work.
PMID- 9635734
TI - A physicochemical approach for predicting the effectiveness of peptide-based gene
delivery systems for use in plasmid-based gene therapy.
AB - Novel synthetic peptides, based on carrier peptide analogs (YKAKnWK) and an
amphipathic peptide (GLFEALLELLESLWELLLEA), have been formulated with DNA
plasmids to create peptide-based gene delivery systems. The carrier peptides are
used to condense plasmids into nanoparticles with a hydrodynamic diameter (DH)
ranging from 40 to 200 nm, which are sterically stable for over 100 h. Size and
morphology of the carrier peptide/plasmid complex have been determined by photon
correlation spectroscopy (PCS) and transmission electron microscopy (TEM),
respectively. The amphipathic peptide is used as a pH-sensitive lytic agent to
facilitate release of the plasmid from endosomes after endocytosis of the
peptide/plasmid complex. Hemolysis assays have shown that the amphipathic peptide
destabilizes lipid bilayers at low pH, mimicking the properties of viral
fusogenic peptides. However, circular dichroism studies show that unlike the
viral fusion peptides, this amphipathic peptide loses some of its alpha-helical
structure at low pH in the presence of liposomes. The peptide-based gene delivery
systems were tested for transfection efficiency in a variety of cell lines,
including 14-day C2C12 mouse myotubes, using gene expression systems containing
the beta-galactosidase reporter gene. Transfection data demonstrate a correlation
between in vitro transfection efficiency and the combination of several physical
properties of the peptide/plasmid complexes, including 1) DNA dose, 2) the zeta
potential of the particle, 3) the requirement of both lytic and carrier peptides,
and 4) the number of lysine residues associated with the carrier peptide.
Transfection data on 14-day C2C12 myotubes utilizing the therapeutic human growth
hormone gene formulated in an optimal peptide gene delivery system show an
increase in gene expression over time, with a maximum in protein levels at 96 h
(approximately 18 ng/ml).
PMID- 9635735
TI - Geometry and physics of catenanes applied to the study of DNA replication.
AB - The concept of ideal geometric configurations was recently applied to the
classification and characterization of various knots. Different knots in their
ideal form (i.e., the one requiring the shortest length of a constant-diameter
tube to form a given knot) were shown to have an overall compactness proportional
to the time-averaged compactness of thermally agitated knotted polymers forming
corresponding knots. This was useful for predicting the relative speed of
electrophoretic migration of different DNA knots. Here we characterize the ideal
geometric configurations of catenanes (called links by mathematicians), i.e.,
closed curves in space that are topologically linked to each other. We
demonstrate that the ideal configurations of different catenanes show
interrelations very similar to those observed in the ideal configurations of
knots. By analyzing literature data on electrophoretic separations of the torus
type of DNA catenanes with increasing complexity, we observed that their
electrophoretic migration is roughly proportional to the overall compactness of
ideal representations of the corresponding catenanes. This correlation does not
apply, however, to electrophoretic migration of certain replication
intermediates, believed up to now to represent the simplest torus-type catenanes.
We propose, therefore, that freshly replicated circular DNA molecules, in
addition to forming regular catenanes, may also form hemicatenanes.
PMID- 9635736
TI - Contributions of linker histones and histone H3 to chromatin structure: scanning
force microscopy studies on trypsinized fibers.
AB - Little is known about the mechanisms that organize linear arrays of nucleosomes
into the three-dimensional structures of extended and condensed chromatin fibers.
We have earlier defined, from scanning force microscopy (SFM) and mathematical
modeling, a set of simple structural determinants of extended fiber morphology,
the critical parameters being the entry-exit angle between consecutive linkers
and linker length. Here we study the contributions of the structural domains of
the linker histones (LHs) and of the N-terminus of histone H3 to extended fiber
morphology by SFM imaging of progressively trypsinized chromatin fibers. We find
that cleavage of LH tails is associated with a lengthening of the
internucleosomal center-to-center distance, and that the somewhat later cleavage
of the N-terminus of histone H3 is associated with a flattening of the fiber. The
persistence of the "zigzag" fiber morphology, even at the latest stages of
trypsin digestion, can be attributed to the retention of the globular domain of
LH in the fiber.
PMID- 9635737
TI - Linker histone tails and N-tails of histone H3 are redundant: scanning force
microscopy studies of reconstituted fibers.
AB - The mechanisms responsible for organizing linear arrays of nucleosomes into the
three-dimensional structure of chromatin are still largely unknown. In a
companion paper (Leuba, S. H., et al. 1998. Biophys. J. 74:2823-2829), we study
the contributions of linker histone domains and the N-terminal tail of core
histone H3 to extended chromatin fiber structure by scanning force microscopy
imaging of mildly trypsinized fibers. Here we complement and extend these studies
by scanning force microscopy imaging of selectively reconstituted chromatin
fibers, which differ in subtle but distinctive ways in their histone composition.
We demonstrate an absolute requirement for the globular domain of the linker
histones and a structural redundancy of the tails of linker histones and of
histone H3 in determining conformational stability.
PMID- 9635738
TI - Direct visualization of dynamic protein-DNA interactions with a dedicated atomic
force microscope.
AB - Photolyase DNA interactions and the annealing of restriction fragment ends are
directly visualized with the atomic force microscope (AFM). To be able to
interact with proteins, DNA must be loosely bound to the surface. When MgCl2 is
used to immobilize DNA to mica, DNA is attached to the surface at distinct sites.
The pieces of DNA in between are free to move over the surface and are available
for protein interaction. After implementation of a number of instrumental
improvements, the molecules can be visualized routinely, under physiological
conditions and with molecular resolution. Images are acquired reproducibly
without visible damage for at least 30 min, at a scan rate of 2 x 2 microm2/min
and a root mean square noise of less than 0.2 nm. Nonspecific photolyase DNA
complexes were visualized, showing association, dissociation, and movement of
photolyase over the DNA. The latter result suggests a sliding mechanism by which
photolyase can scan DNA for damaged sites. The experiments illustrate the
potential that AFM presents for modern molecular biology.
PMID- 9635739
TI - Deexcitation of cardiac cells.
AB - Excitation and deexcitation are fundamental phenomena in the electrophysiology of
excitable cells. Both of them can be induced by stimulating a cell with
intracellularly injected currents. With extracellular stimulation, deexcitation
was never observed; only cell excitation was found. Why? A generic model with two
variables (FitzHugh) predicts that an extracellular stimulus can both excite the
cell and terminate the action potential (AP). Our experiments with single mouse
myocytes have shown that short (2-5 ms) extracellular pulses never terminated the
AP. This result agrees with our numerical experiments with the Beeler-Reuter
model. To analyze the problem, we exploit the separation of time scales to derive
simplified models with fewer equations. Our analysis has shown that the very
specific form of the current-voltage (I-V) characteristics of the time
independent potassium current (almost no dependence on voltage for positive
membrane potentials) is responsible here. When the shape of the I-V
characteristics of potassium currents was modified to resemble that in ischemic
tissues, or when the external potassium concentration (K0) is increased, the AP
was terminated by extracellular pulses. These results may be important for
understanding the mechanisms of defibrillation.
PMID- 9635741
TI - Multivariate curve resolution: a possible tool in the detection of intermediate
structures in protein folding.
AB - Different multivariate data analysis techniques based on factor analysis and
multivariate curve resolution are shown for the study of biochemical evolutionary
processes like conformational changes and protein folding. Several simulated CD
spectral data sets describing different hypothetical protein folding pathways are
analyzed and discussed in relation to the feasibility of factor analysis
techniques to detect and resolve the number of components needed to explain the
evolution of the CD spectra corresponding to the process (i.e., to detect the
presence of intermediate forms). When more than two components (the native and
unordered forms) are needed to explain the evolution of the spectra, an iterative
multivariate curve resolution procedure based on an alternating least squares
algorithm is proposed to estimate the CD spectrum corresponding to the
intermediate form.
PMID- 9635740
TI - Spontaneous-curvature theory of clathrin-coated membranes.
AB - Clathrin-coated membranes are precursors to coated vesicles in the receptor
mediated endocytic pathway. In this paper we present a physical model for the
first steps of the transformation of a clathrin-coated membrane into a coated
vesicle. The theory is based on in vitro cytoplasmic acidification experiments of
Heuser (J. Cell Biol. 108:401-411) that suggest the transformation proceeds by
changes in the chemical environment of the clathrin lattice, wherein the chemical
environment determines the amount of intrinsic, or spontaneous, curvature of the
network. We show that a necessary step of the transformation, formation of free
pentagons in the clathrin network, can proceed via dislocation unbinding, driven
by changes in the spontaneous curvature. Dislocation unbinding is shown to favor
formation of coated vesicles that are quite small compared to those predicted by
the current continuum theories, which do not include the topology of the clathrin
lattice.
PMID- 9635743
TI - Derivation of unstirred-layer transport number equations from the Nernst-Planck
flux equations.
AB - Since the late 1960s it has been known that the passage of current across a
membrane can give rise to local changes in salt concentration in unstirred layers
or regions adjacent to that membrane, which in turn give rise to the development
of slow transient diffusion potentials and osmotic flows across those membranes.
These effects have been successfully explained in terms of transport number
discontinuities at the membrane-solution interface, the transport number of an
ion reflecting the proportion of current carried by that ion. Using the standard
definitions for transport numbers and the regular diffusion equations, these
polarization or transport number effects have been analyzed and modeled in a
number of papers. Recently, the validity of these equations has been questioned.
This paper has demonstrated that, by going back to the Nernst-Planck flux
equations, exactly the same resultant equations can be derived and therefore that
the equations derived directly from the transport number definitions and standard
diffusion equations are indeed valid.
PMID- 9635742
TI - Electromechanical coupling model of gating the large mechanosensitive ion channel
(MscL) of Escherichia coli by mechanical force.
AB - We have developed a theoretical electromechanical coupling (EMC) model of gating
of the large-conductance mechanosensitive ion channel (MscL). The model presents
the first attempt to explain the pressure-dependent transitions between the
closed and open channel conformations on a molecular level by assuming 1) a
homohexameric structural model of the channel, 2) electrostatic interactions
between various domains of the homohexamer, 3) structural flexibility of the N
terminal portion of the monomer, and 4) mechanically and electrostatically
induced displacement of the N-terminal domain relative to other structural
domains of the protein. In the EMC model, 12 membrane-spanning alpha-helices (six
each of the M1 and M2 transmembrane domains of the MscL monomer), are envisaged
to line the channel pore with a diameter of 40 A, whereas the N- and C-termini
are oriented toward each other inside the pore when the channel is closed. The
model proposes that stretching the membrane bilayer by mechanical force causes
the monomers to be pulled away from and slightly tilted toward each other. This
relative movement of alpha-helices could serve as a trigger to initiate a "swing
like" motion of the N-terminus around the glycine residue G14 that may act as a
pivot. The analysis of the attractive and repulsive coulomb forces between all
domains of the channel homohexamer suggested that an inclination angle of
approximately 3.0 degrees - 4.1 degrees between the oppositely oriented channel
monomers should suffice for the N-terminus to turn away from other domains
causing the channel to open. According to the EMC model the minimal free energy
change, deltaG, that could initiate the opening of the channel was 2 kT. Also,
the model predicted that the negative pressure required for channel open
probability, Po = 0.5, should be between 50 and 80 mmHg. These values were in a
good agreement with the experimentally estimated pressures of 60-70 mmHg obtained
with the MscL reconstituted in liposomes. Furthermore, consistent with a notion
that the N-terminus may present a mechanosensitive structural element providing a
mechanism to open the MscL by mechanical force, the model provides a simple
explanation for the variations in pressure sensitivity observed with several MscL
mutants having either deletions or substitutions in N- or C-terminus, or site
directed mutations in the S2-S3 loop.
PMID- 9635744
TI - Importance of explicit salt ions for protein stability in molecular dynamics
simulation.
AB - The accurate and efficient treatment of electrostatic interactions is one of the
challenging problems of molecular dynamics simulation. Truncation procedures such
as switching or shifting energies or forces lead to artifacts and significantly
reduced accuracy. The particle mesh Ewald (PME) method is one approach to
overcome these problems by providing a computationally efficient means of
calculating all long-range electrostatic interactions in a periodic simulation
box by use of fast Fourier transformation techniques. For the application of the
PME method to the simulation of a protein with a net charge in aqueous solution,
counterions are added to neutralize the system. The usual procedure is to add
charge-balancing counterions close to charged residues to neutralize the protein
surface. In the present article, we show that for MD simulation of a small
protein of marginal stability, the YAP-WW domain, explicit modeling of 0.2 M
ionic strength (in addition to the charge-balancing counterions) is necessary to
maintain a stable protein structure. Without explicit ions throughout the
periodic simulation box, the charge-balancing counterions on the protein surface
diffuse away from the protein, resulting in destruction of the beta-sheet
secondary structure of the WW domain.
PMID- 9635745
TI - Streaming potentials in gramicidin channels measured with ion-selective
microelectrodes.
AB - Streaming potentials have been measured for gramicidin channels with a new method
employing ion-selective microelectrodes. It is shown that ideally ion-selective
electrodes placed at the membrane surface record the true streaming potential.
Using this method for ion concentrations below 100 mM, approximately seven water
molecules are transported whenever a sodium, potassium, or cesium ion, passes
through the channel. This new method confirms earlier measurements (Rosenberg,
P.A., and A. Finkelstein. 1978. Interaction of ions and water in gramicidin A
channels. J. Gen. Physiol. 72:327-340) in which the streaming potentials were
calculated as the difference between electrical potentials measured in the
presence of gramicidin and in the presence of the ion carriers valinomycin and
nonactin.
PMID- 9635746
TI - Cluster organization of ion channels formed by the antibiotic syringomycin E in
bilayer lipid membranes.
AB - The cyclic lipodepsipeptide, syringomycin E, when incorporated into planar lipid
bilayer membranes, forms two types of channels (small and large) that are
different in conductance by a factor of sixfold. To discriminate between a
cluster organization-type channel structure and other possible different
structures for the two channel types, their ionic selectivity and pore size were
determined. Pore size was assessed using water-soluble polymers. Ion selectivity
was found to be essentially the same for both the small and large channels. Their
reversal (zero current) potentials with the sign corresponding to anionic
selectivity did not differ by more than 3 mV at a twofold electrolyte gradient
across the bilayer. Reduction in the single-channel conductance induced by
poly(ethylene glycol)s of different molecular weights demonstrated that the
aqueous pore sizes of the small and large channels did not differ by more than 2%
and were close to 1 nm. Based on their virtually identical selectivity and size,
we conclude that large syringomycin E channels are clusters of small ones
exhibiting synchronous opening and closing.
PMID- 9635747
TI - The sensor regions of VDAC are translocated from within the membrane to the
surface during the gating processes.
AB - The motion of the sensor regions in a mitochondrial voltage-gated channel called
VDAC were probed by attaching biotin at specific locations and determining its
ability to bind to added streptavidin. Site-directed mutagenesis was used to
introduce single cysteine residues into Neurospora crassa VDAC (naturally lacks
cysteine). These were chemically biotinylated and reconstituted into planar
phospholipid membranes. In the 19 sites examined, only two types of results were
observed upon streptavidin addition: in type 1, channel conductance was reduced,
but voltage gating could proceed; in type 2, channels were locked in a closed
state. The result at type 1 sites is interpreted as streptavidin binding to sites
in static regions close to the channel opening. The binding sterically interferes
with ion flow. The result at type 2 sites indicates that these are located on a
mobile domain and coincide with the previously identified sensor regions. The
findings are consistent with closure resulting from the movement of a domain from
within the transmembrane regions to the membrane surface. No single site was
accessible to streptavidin from both membrane surfaces, indicating that the
motion is limited. From the streptavidin-induced reduction in conductance at type
1 sites, structural information was obtained about the location of these sites.
PMID- 9635748
TI - Slow inactivation in human cardiac sodium channels.
AB - The available pool of sodium channels, and thus cell excitability, is regulated
by both fast and slow inactivation. In cardiac tissue, the requirement for
sustained firing of long-duration action potentials suggests that slow
inactivation in cardiac sodium channels may differ from slow inactivation in
skeletal muscle sodium channels. To test this hypothesis, we used the macropatch
technique to characterize slow inactivation in human cardiac sodium channels
heterologously expressed in Xenopus oocytes. Slow inactivation was isolated from
fast inactivation kinetically (by selectively recovering channels from fast
inactivation before measurement of slow inactivation) and structurally (by
modification of fast inactivation by mutation of IFM1488QQQ). Time constants of
slow inactivation in cardiac sodium channels were larger than previously reported
for skeletal muscle sodium channels. In addition, steady-state slow inactivation
was only 40% complete in cardiac sodium channels, compared to 80% in skeletal
muscle channels. These results suggest that cardiac sodium channel slow
inactivation is adapted for the sustained depolarizations found in normally
functioning cardiac tissue. Complete slow inactivation in the fast inactivation
modified IFM1488QQQ cardiac channel mutant suggests that this impairment of slow
inactivation may result from an interaction between fast and slow inactivation.
PMID- 9635749
TI - The N-terminus of the K channel KAT1 controls its voltage-dependent gating by
altering the membrane electric field.
AB - Functional roles of different domains (pore region, S4 segment, N-terminus) of
the KAT1 potassium channel in its voltage-dependent gating were
electrophysiologically studied in Xenopus oocytes. The KAT1 properties did not
depend on the extracellular K+ concentration or on residue H267, equivalent to
one of the residues known to be important in C-type inactivation in Shaker
channels, indicating that the hyperpolarization-induced KAT1 inward currents are
related to the channel activation rather than to recovery from inactivation.
Neutralization of a positively charged amino acid in the S4 domain (R176S)
reduced the gating charge movement, suggesting that it acts as a voltage-sensing
residue in KAT1. N-terminal deletions alone (e.g., delta20-34) did not affect the
gating charge movement. However, the deletions paradoxically increased the
voltage sensitivity of the R176S mutant channel, but not that of the wild-type
channel. We propose a simple model in which the N-terminus determines the KAT1
voltage sensitivity by contributing to the electric field sensed by the voltage
sensor.
PMID- 9635750
TI - A novel voltage clamp technique for mapping ionic currents from cultured skeletal
myotubes.
AB - The biophysical properties and cellular distribution of ion channels largely
determine the input/output relationships of electrically excitable cells. A
variety of patch pipette voltage clamp techniques are available to characterize
ionic currents. However, when used by themselves, such techniques are not well
suited to the task of mapping low-density channel distributions. We describe here
a new voltage clamp method (the whole cell loose patch (WCLP) method) that
combines whole-cell recording through a tight-seal pipette with focal
extracellular stimulation through a loose-seal pipette. By moving the stimulation
pipette across the cell surface and using a stationary whole-cell pipette to
record the evoked patch currents, this method should be suitable for mapping
channel distributions, even on large cells possessing low channel densities. When
we applied this method to the study of currents in cultured chick myotubes, we
found that the cell cable properties and the series resistance of the recording
pipette caused significant filtering of the membrane currents, and that the
filter characteristics depended in part upon the distance between the stimulating
and recording pipettes. We describe here how we determined the filter impulse
response for each loose-seal pipette placement and subsequently recovered
accurate estimates of patch membrane current through deconvolution.
PMID- 9635751
TI - Formation of giant liposomes promoted by divalent cations: critical role of
electrostatic repulsion.
AB - Spontaneous formation of giant unilamellar liposomes in a gentle hydration
process, as well as the adhesion energy between liposomal membranes, has been
found to be dependent on the concentration of divalent alkali cations, Ca2+ or
Mg2+, in the medium. With electrically neutral phosphatidylcholine (PC), Ca2+ or
Mg2+ at 1-30 mM greatly promoted liposome formation compared to low yields in
nonelectrolyte or potassium chloride solutions. When negatively charged
phosphatidylglycerol (PG) was mixed at 10%, the yield was high in nonelectrolytes
but liposomes did not form at 3-10 mM CaCl2. In the adhesion test with
micropipette manipulation, liposomal membranes adhered to each other only in a
certain range of CaCl2 concentrations, which agreed with the range where liposome
did not form. The adhesion range shifted to higher Ca2+ concentrations as the
amount of PG was increased. These results indicate that the divalent cations bind
to and add positive charges to the lipids, and that membranes are separated and
stabilized in the form of unilamellar liposomes when net charges on the membranes
produce large enough electrostatic repulsion. Under the assumption that the
maximum of adhesion energy within an adhesive range corresponds to exact charge
neutralization by added Ca2+, association constants of PC and PG for Ca2+ were
estimated at 7.3 M(-1) and 86 M(-1), respectively, in good agreement with
literature values.
PMID- 9635753
TI - Effect of extrusion pressure and lipid properties on the size and polydispersity
of lipid vesicles.
AB - The production of vesicles, spherical shells formed from lipid bilayers, is an
important aspect of their recent application to drug delivery technologies. One
popular production method involves pushing a lipid suspension through cylindrical
pores in polycarbonate membranes. However, the actual mechanism by which the
polydisperse, multilamellar lipid suspension breaks up into a relatively
monodisperse population of vesicles is not well understood. To learn about
factors influencing this process, we have characterized vesicles produced under
different extrusion parameters and from different lipids. We find that extruded
vesicles are only produced above a certain threshold extrusion pressure and have
sizes that depend on the extrusion pressure. The minimum pressure appears to be
associated with the lysis tension of the lipid bilayer rather than any bending
modulus of the system. The flow rate of equal concentration lipid solutions
through the pores, after being corrected for the viscosity of water, is
independent of lipid properties.
PMID- 9635752
TI - Phase transitions in films of lung surfactant at the air-water interface.
AB - Pulmonary surfactant maintains a putative surface-active film at the air-alveolar
fluid interface and prevents lung collapse at low volumes. Porcine lung
surfactant extracts (LSE) were studied in spread and adsorbed films at 23 +/- 1
degrees C using epifluorescence microscopy combined with surface balance
techniques. By incorporating small amounts of fluorescent probe 1-palmitoyl-2
nitrobenzoxadiazole dodecanoyl phosphatidylcholine (NBD-PC) in LSE films the
expanded (fluid) to condensed (gel-like) phase transition was studied under
different compression rates and ionic conditions. Films spread from solvent and
adsorbed from vesicles both showed condensed (probe-excluding) domains dispersed
in a background of expanded (probe-including) phase, and the appearance of the
films was similar at similar surface pressure. In quasistatically compressed LSE
films the appearance of condensed domains occurred at a surface pressure (pi) of
13 mN/m. Such domains increased in size and amounts as pi was increased to 35
mN/m, and their amounts appeared to decrease to 4% upon further compression to 45
mN/m. Above pi of 45 mN/m the LSE films had the appearance of filamentous
materials of finely divided dark and light regions, and such features persisted
up to a pi near 68 mN/m. Some of the condensed domains had typical kidney bean
shapes, and their distribution was similar to those seen previously in films of
dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant. Rapid
cyclic compression and expansion of LSE films resulted in features that indicated
a possible small (5%) loss of fluid components from such films or an increase in
condensation efficiency over 10 cycles. Calcium (5 mM) in the subphase of LSE
films altered the domain distribution, decreasing the size and increasing the
number and total amount of condensed phase domains. Calcium also caused an
increase in the value of pi at which the maximum amount of independent condensed
phase domains were observed to 45 mN/m. It also induced formation of large
amounts of novel, nearly circular domains containing probe above pi of 50 mN/m,
these domains being different in appearance than any seen at lower pressures with
calcium or higher pressures in the absence of calcium. Surfactant protein-A (SP
A) adsorbed from the subphase onto solvent-spread LSE films, and aggregated
condensed domains in presence of calcium. This study indicates that spread or
adsorbed lung surfactant films can undergo expanded to condensed, and possibly
other, phase transitions at the air-water interface as lateral packing density
increases. These phase transitions are affected by divalent cations and SP-A in
the subphase, and possibly by loss of material from the surface upon cyclic
compression and expansion.
PMID- 9635754
TI - Kinetics of synaptic depression and vesicle recycling after tetanic stimulation
of frog motor nerve terminals.
AB - We measured the time courses of two key components of the synaptic vesicle cycle
during recovery from synaptic depression under different conditions, and used
this and other information to create a kinetic model of the vesicle cycle. End
plate potential (EPP) amplitudes were used to follow recovery from synaptic
depression after different amounts of tetanic stimulation. This provided an
estimate of the time course of vesicle mobilization from the reserve pool to the
docked (readily releasable) pool. In addition, FM1-43 was used to measure the
rate of membrane retrieval after tetanic stimulation, and the amount of membrane
transferred to the surface membrane. This provided a measure of the rate of
refilling of the reserve pool with recycled vesicles. The time courses of both
synaptic depression and endocytosis were slowed by prolonged tetanic stimulation.
This behavior could be fitted by a simple model, assuming a first-order kinetics
for both vesicle endocytosis and mobilization. The results show that a nearly 20
fold decrease in the rate constant of endocytosis greatly delays refilling of the
depleted reserve pool. However, to fully account for the slower recovery of
depression, a decrease in the rate constant of vesicle mobilization from the
reserve pool of about sixfold is also required.
PMID- 9635755
TI - Intensive extrusion and occlusion of water in ganglioside micelles with thermal
reversibility.
AB - By using a shell-modeling analysis for small-angle scattering data of ganglioside
micellar dispersion, we recently reported that the elevation of temperature
induces a significant shrinkage of the hydrophilic region of the ganglioside
micelle, suggesting that the oligosaccharide chains with sialic acid residues of
ganglioside molecules change the conformation, sensitively responding to a change
in temperature (Hirai et al., 1996. Biophys. J. 70:1761-1768; J. Phys. Chem.
100:11675-11680). We have carried out further analyses of the temperature
dependence of the structural parameters reported previously, and we have found
clear evidence of reversible extrusion and occlusion of a large amount of water
in the hydrophilic region of the ganglioside micelle in the physiological
temperature range of 6-60 degrees C. The present results suggest a remarkable
function of ganglioside molecules: they change the hydrophilicity of the cell
surface locally as a response to variations in temperature. This phenomenon might
be involved in various surface events, such as cell-cell interaction and cell
surface-protein interaction.
PMID- 9635756
TI - Control by osmotic pressure of voltage-induced permeabilization and gene transfer
in mammalian cells.
AB - Cells can be transiently permeabilized by a membrane potential difference
increase induced by the application of high electric pulses. This was shown to be
under the control of the pulsing buffer osmotic pressure, when short pulses were
applied. In this paper, the effects of buffer osmotic pressure during electric
treatment and during the following 10 min were investigated in Chinese hamster
ovary cells subjected to long (ms) square wave pulses, a condition needed to
mediate gene transfer. No effect on cell permeabilization for a small molecule
such as propidium iodide was observed. The use of a hypoosmolar buffer during
pulsation allows more efficient loading of cells with beta-galactosidase, a
tetrameric protein, but no effect of the postpulse buffer osmolarity was
observed. The resulting expression of plasmid coding for beta-galactosidase was
strongly controlled by buffer osmolarity during as well as after the pulse. The
results, tentatively explained in terms of the effect of osmotic pressure on cell
swelling, membrane organization, and interaction between molecules and membrane,
support the existence of key steps in plasmid-membrane interaction in the
mechanism of cell electrically mediated gene transfer.
PMID- 9635757
TI - Structural features that modulate the transmembrane migration of a hydrophobic
peptide in lipid vesicles.
AB - Two approaches employing nuclear magnetic resonance (NMR) were used to
investigate the transmembrane migration rate of the C-terminal end of native
alamethicin and a more hydrophobic analog called L1. Native alamethicin exhibits
a very slow transmembrane migration rate when bound to phosphatidylcholine
vesicles, which is no greater than 1 x 10(-4) min(-1). This rate is much slower
than expected, based on the hydrophobic partition energies of the amino acid side
chains and the backbone of the exposed C-terminal end of alamethicin. The
alamethicin analog L1 exhibits crossing rates that are at least 1000 times faster
than that of native alamethicin. A comparison of the equilibrium positions of
these two peptides shows that L1 sits approximately 3-4 A deeper in the membrane
than does native alamethicin (Barranger-Mathys and Cafiso. 1996. Biochemistry.
35:489). The slow rate of alamethicin crossing can be explained if the peptide
helix is irregular at its C-terminus and hydrogen bonded to solvent or lipid. We
postulate that L1 does not experience as large a barrier to transport because its
C-terminus is already buried within the membrane interface. This difference is
most easily explained by conformational differences between L1 and alamethicin
rather than differences in hydrophobicity. The results obtained here demonstrate
that side-chain hydrophobicity alone cannot account for the energy barriers to
peptide and protein transport across membranes.
PMID- 9635758
TI - Interaction of lipophilic ions with the plasma membrane of mammalian cells
studies by electrorotation.
AB - The electrical properties of biological and artificial membranes were studied in
the presence of a number of negatively charged tungsten carbonyl complexes, such
as [W(CO)5(CN)]- , [W(CO)5(NCS)]-, [W2(CO)10(CN)]-, and [W(CO)5(SCH2C6H5)]-,
using the single-cell electrorotation and the charge-pulse relaxation techniques.
Most of the negatively charged tungsten complexes were able to introduce mobile
charges into the membranes, as judged from electrorotation spectra and relaxation
experiments. This means that the tungsten derivatives act as lipophilic anions.
They greatly contributed to the polarizability of the membranes and led to a
marked dielectric dispersion (frequency dependence of the membrane capacitance
and conductance). The increment and characteristic frequency of the dispersion
reflect the structure, environment, and mobility of the charged probe molecule in
electrorotation experiments with biological membranes. The partition coefficients
and the translocation rate constants derived from the electrorotation spectra of
cells agreed well with the corresponding data obtained from charge-pulse
experiments on artificial lipid bilayers.
PMID- 9635759
TI - ATP analogs and muscle contraction: mechanics and kinetics of nucleoside
triphosphate binding and hydrolysis.
AB - The mechanical behavior of skinned rabbit psoas muscle fiber contractions and in
vitro motility of F-actin (Vf) have been examined using ATP, CTP, UTP, or their 2
deoxy forms (collectively designated as nucleotide triphosphates or NTPs) as
contractile substrates. Measurements of actin-activated heavy meromyosin (HMM)
NTPase, the rates of NTP binding to myosin and actomyosin, NTP-mediated acto-HMM
dissociation, and NTP hydrolysis by acto-HMM were made for comparison to the
mechanical results. The data suggest a very similar mechanism of acto-HMM NTP
hydrolysis. Whereas all NTPs studied support force production and stiffness that
vary by a factor 2 or less, the unloaded shortening velocity (Vu) of muscle
fibers varies by almost 10-fold. 2-Deoxy ATP (dATP) was unique in that Vu was 30%
greater than with ATP. Parallel behavior was observed between Vf and the steady
state maximum actin-activated HMM ATPase rate. Further comparisons suggest that
the variation in force correlates with the rate and equilibrium constant for NTP
cleavage; the variations in Vu or Vf are related to the rate of cross-bridge
dissociation caused by NTP binding or to the rate(s) of product release.
PMID- 9635760
TI - The effect of ATP analogs on posthydrolytic and force development steps in
skinned skeletal muscle fibers.
AB - ATP, 2-deoxy ATP (dATP), CTP, and UTP support isometric force and unloaded
shortening velocity (Vu) to various extents (Regnier et al., Biophys. J. 74:3044
3058). Vu correlated with the rate of cross-bridge dissociation after the power
stroke and the steady-state hydrolysis rate in solution, whereas force was
modulated by NTP binding and cleavage. Here we studied the influence of
posthydrolytic cross-bridge steps on force and fiber shortening by measuring
isometric force and stiffness, the rate of tension decline (kPi) after Pi
photogeneration from caged Pi, and the rate of tension redevelopment (ktr) after
a sudden release and restretch of fibers. The slope of the force versus [Pi]
relationship was the same for ATP, dATP, and CTP, but for UTP it was threefold
less. ktr and kPi increased with increasing [Pi] with a similar slope for ATP,
dATP, and CTP, but had an increasing magnitude of the relationship ATP < dATP <
CTP. UTP reduced ktr but increased kPi. The results suggest that the rate
constant for the force-generating isomerization increases with the order ATP <
dATP < CTP < UTP. Simulations using a six-state model suggest that increasing the
force-generating rate accounts for the faster kPi in dATP, CTP, and UTP. In
contrast, ktr appears to be strongly affected by the rates of NTP binding and
cleavage and the rate of the force-generating isomerization.
PMID- 9635761
TI - Characterizations of cross-bridges in the presence of saturating concentrations
of MgAMP-PNP in rabbit permeabilized psoas muscle.
AB - Several earlier studies have led to different conclusions about the complex of
myosin with MgAMP-PNP. It has been suggested that subfragment 1 of myosin (S1)
MgAMP-PNP forms an S1-MgADP-like state, an intermediate between the myosin S1
MgATP and myosin S1-MgADP states or a mixture of cross-bridge states. We suggest
that the different states observed result from the failure to saturate S1 with
MgAMP-PNP. At saturating MgAMP-PNP, the interaction of myosin S1 with actin is
very similar to that which occurs in the presence of MgATP. 1) At 1 degrees C and
170 mM ionic strength the equatorial x-ray diffraction intensity ratio I11/I10
decreased with an increasing MgAMP-PNP concentration and leveled off by
approximately 20 mM MgAMP-PNP. The resulting ratio was the same for MgATP-relaxed
fibers. 2) The two dimensional x-ray diffraction patterns from MgATP-relaxed and
MgAMP-PNP-relaxed bundles are similar. 3) The affinity of S1-MgAMP-PNP for the
actin-tropomyosin-troponin complex in solution in the absence of free calcium is
comparable with that of S1-MgATP. 4) In the presence of calcium, I11/I10
decreased toward the relaxed value with increasing MgAMP-PNP, signifying that the
affinity between cross-bridge and actin is weakened by MgAMP-PNP. 5) The degree
to which the equatorial intensity ratio decreases as the ionic strength increases
is similar in MgAMP-PNP and MgATP. Therefore, results from both fiber and
solution studies suggest that MgAMP-PNP acts as a non hydrolyzable MgATP analogue
for myosin.
PMID- 9635762
TI - Steady-state fluorescence polarization studies of the orientation of myosin
regulatory light chains in single skeletal muscle fibers using pure isomers of
iodoacetamidotetramethylrhodamine.
AB - The regulatory light chain (RLC) from chicken gizzard myosin was covalently
modified on cysteine 108 with either the 5- or 6-isomer of
iodoacetamidotetramethylrhodamine (IATR). Labeled RLCs were purified by fast
protein liquid chromatography and characterized by reverse-phase high-performance
liquid chromatography (HPLC), tryptic digestion, and electrospray mass
spectrometry. Labeled RLCs were exchanged into the native myosin heads of single
skinned fibers from rabbit psoas muscle, and the ATR dipole orientations were
determined by fluorescence polarization. The 5- and 6-ATR dipoles had distinct
orientations, and model orientational distributions suggest that they are more
than 20 degrees apart in rigor. In the rigor-to-relaxed transition (sarcomere
length 2.4 microm, 10 degrees C), the 5-ATR dipole became more perpendicular to
the fiber axis, but the 6-ATR dipole became more parallel. This orientation
change was absent at sarcomere length 4.0 microm, where overlap between myosin
and actin filaments is abolished. When the temperature of relaxed fibers was
raised to 30 degrees C, the 6-ATR dipoles became more parallel to the fiber axis
and less ordered; when ionic strength was lowered from 160 mM to 20 mM (5 degrees
C), the 6-ATR dipoles became more perpendicular to the fiber axis and more
ordered. In active contraction (10 degrees C), the orientational distribution of
the probe dipoles was similar but not identical to that in relaxation, and was
not a linear combination of the orientational distributions in relaxation and
rigor.
PMID- 9635763
TI - Fluorescence polarization transients from rhodamine isomers on the myosin
regulatory light chain in skeletal muscle fibers.
AB - Fluorescence polarization was used to examine orientation changes of two
rhodamine probes bound to myosin heads in skeletal muscle fibers. Chicken gizzard
myosin regulatory light chain (RLC) was labeled at Cys108 with either the 5- or
the 6-isomer of iodoacetamidotetramethylrhodamine (IATR). Labeled RLC (termed
Cys108-5 or Cys108-6) was exchanged for the endogenous RLC in single, skinned
fibers from rabbit psoas muscle. Three independent fluorescence polarization
ratios were used to determine the static angular distribution of the probe
dipoles with respect to the fiber axis and the extent of probe motions on the
nanosecond time scale of the fluorescence lifetime. We used step changes in fiber
length to partially synchronize the transitions between biochemical, structural,
and mechanical states of the myosin cross-bridges. Releases during active
contraction tilted the Cys108-6 dipoles away from the fiber axis. This response
saturated for releases beyond 3 nm/half-sarcomere (h.s.). Stretches in active
contraction caused the dipoles to tilt toward the fiber axis, with no evidence of
saturation for stretches up to 7 nm/h.s. These nonlinearities of the response to
length changes are consistent with a partition of approximately 90% of the probes
that did not tilt when length changes were applied and 10% of the probes that
tilted. The responding fraction tilted approximately 30 degrees for a 7.5 nm/h.s.
release and traversed the plane perpendicular to the fiber axis for larger
releases. Stretches in rigor tilted Cys108-6 dipoles away from the fiber axis,
which was the opposite of the response in active contraction. The transition from
the rigor-type to the active-type response to stretch preceded the main force
development when fibers were activated from rigor by photolysis of caged ATP in
the presence of Ca2+. Polarization ratios for Cys108-6 in low ionic strength (20
mM) relaxing solution were compatible with a combination of the relaxed (200 mM
ionic strength) and rigor intensities, but the response to length changes was of
the active type. The nanosecond motions of the Cys108-6 dipole were restricted to
a cone of approximately 20 degrees half-angle, and those of Cys108-5 dipole to a
cone of approximately 25 degrees half-angle. These values changed little between
relaxation, active contraction, and rigor. Cys108-5 showed very small-amplitude
tilting toward the fiber axis for both stretches and releases in active
contraction, but much larger amplitude tilting in rigor. The marked differences
in these responses to length steps between the two probe isomers and between
active contraction and rigor suggest that the RLC undergoes a large angle change
(approximately 60 degrees) between these two states. This motion is likely to be
a combination of tilting of the RLC relative to the fiber axis and twisting of
the RLC about its own axis.
PMID- 9635764
TI - Localization of Cys133 of rabbit skeletal troponin-I with respect to troponin-C
by resonance energy transfer.
AB - We have used the technique of resonance energy transfer in conjunction with
distance geometry analysis to localize Cys133 of troponin-I (TnI) with respect to
troponin-C (TnC) in the ternary troponin complex and the binary TnC.TnI complex
in the presence and absence of Ca2+. Cys133 of TnI was chosen because our
previous work has shown that the region of TnI containing this residue undergoes
Ca2+-dependent movements between actin and TnC, and may play an important role in
the regulatory function of troponin. For this purpose, a TnI mutant with a single
Cys at position 133, and TnC mutants, each with a single Cys at positions 5, 12,
21, 41, 49, 89, 98, 133, and 158, were constructed by site-directed mutagenesis.
The distances between TnI Cys133 and each of the nine residues in TnC were then
measured. Using a least-squares minimization procedure, we determined the
position of TnI Cys133 in the coordinate system of the crystal structure of TnC.
Our results show that in the presence of Ca2+, TnI Cys133 is located near residue
12 beneath the N-terminal lobe of TnC, and moves away by 12.6 A upon the removal
of Ca2+. TnI Cys133 and the region of TnC that undergoes major change in
conformation in response to Ca2+ are located roughly on opposite sides of TnC's
central helix. This suggests that the region in TnI that undergoes Ca2+-dependent
interaction with TnC is distinct from that interacting with actin.
PMID- 9635766
TI - Molecular mechanics studies on the conformations of 2',3'-dideoxy-2',3'
didehydroguanine nucleoside, D4G.
AB - Conformational energy calculations have been presented on guanine nucleoside in
which the furanose ring is replaced by 2',3'-dideoxy-2',3'-didehydrofuran using
molecular mechanics and conformational analysis. Conformational energies have
been evaluated using the MM2 and AMBER94 force field parameters at two different
dielectric constants. The results are presented in terms of isoenergy contours in
the conformational space of the glycosidic (chi) and C4'-C5' (gamma) bonds
torsions. In general, the chi-gamma interrelationships differ from the
corresponding plots for unmodified nucleosides and nucleotides, reported
previously. Consistency of the calculated preferred conformations with the x-ray
data is sensitive to the force field employed.
PMID- 9635765
TI - ATPase and shortening rates in frog fast skeletal myofibrils by time-resolved
measurements of protein-bound and free Pi.
AB - Shortening and ATPase rates were measured in Ca2+-activated myofibrils from frog
fast muscles in unloaded conditions at 4 degrees C. ATPase rates were determined
using the phosphate-binding protein method (free phosphate) and quench flow
(total phosphate). Shortening rates at near zero load (V0) were estimated by
quenching reaction mixtures 50 ms to 10 s old at pH 3.5 and measuring sarcomere
lengths under the optical microscope. As with the rabbit psoas myofibrils (C.
Lionne, F. Travers, and T. Barman, 1996, Biophys. J. 70:887-895), the ATPase
progress curves had three phases: a transient Pi burst, a fast linear phase (kF),
and a deceleration to a slow phase (kS). Evidence is given that kF is the ATPase
rate of shortening myofibrils. V0 is in good agreement with mechanical
measurements in myofibrils and fibers. Under the same conditions and at
saturation in ATP, V0 and kF are 2.4 microm half-sarcomere(-1) s(-1) and 4.6 s(
1), and their Km values are 33 and 200 microM, respectively. These parameters are
higher than found with rabbit psoas myofibrils. The myofibrillar kF is higher
than the fiber ATPase rates obtained previously in frog fast muscles but
considerably lower than obtained in skinned fibers by the phosphate-binding
protein method (Z. H. He, R. K. Chillingworth, M. Brune, J. E. T. Corrie, D. R.
Trentham, M. R. Webb, and M. R. Ferenczi, 1997, J. Physiol. 50:125-148). We show
that, with frog as with rabbit myofibrillar ATPase, phosphate release is the rate
limiting step.
PMID- 9635767
TI - Effects of supercoiling in electrophoretic trapping of circular DNA in
polyacrylamide gels.
AB - Electrophoretic velocity and orientation have been used to study the electric
field-induced trapping of supercoiled and relaxed circular DNA (2926 and 5386 bp)
in polyacrylamide gels (5% T, 3.3% C) at 7.5-22.5 V/cm, using as controls linear
molecules of either the same contour length or the same radius of gyration. The
circle-specific trapping is reversible. From the duration of the reverse pulse
needed to detrap the molecules, the average trap depth is estimated to be 90 A,
which is consistent with the molecular charge and the field strengths needed to
keep molecules trapped. Trapped circles exhibit a strong field alignment compared
to the linear form, and there is a good correlation between the enhanced field
alignment for the circles and the onset of trapping in both constant and pulsed
fields. The circles do not exhibit the orientation overshoot response to a field
pulse seen with linear DNA, and the rate of orientation growth scales as E(-2+/
0.1) with the field, as opposed to E(-1.1+/-0.1) for the linear form. These
results show that the linear form migrates by cyclic reptation, whereas the
circles most likely are trapped by impalement on gel fibers. This proposal is
supported by very similar velocity and orientation behavior of circular DNA in
agarose gels, where impalement has been deemed more likely because of stiffer gel
fibers. The trapping efficiency is sensitive to DNA topology, as expected for
impalement. In polyacrylamide the supercoiled form (superhelical density sigma =
0.05) has a two- to fourfold lower probability of trapping than the corresponding
relaxed species, whereas in agarose gels the supercoiled form is not trapped at
all. These results are consistent with existing data on the average holes in the
plectonemic supercoiled structures and the fiber thicknesses in the two gel
types. On the basis of the topology effect, it is argued that impalement during
pulsed-field electrophoresis in polyacrylamide gels may be useful for the
separation of more intricate DNA structures such as knots. The results also
indicate that linear dichroism on field-aligned molecules can be used to measure
the supercoiling angle, if relaxed DNA circles are used as controls for the
global degree of orientation.
PMID- 9635768
TI - DNA bending by small, mobile multivalent cations.
AB - We propose a purely electrostatic mechanism by which small, mobile, multivalent
cations can induce DNA bending. A multivalent cation binds at the entrance to the
B-DNA major groove, between the two phosphate strands, electrostatically
repelling sodium counterions from the neighboring phosphates. The unscreened
phosphates on both strands are strongly attracted to the groove-bound cation.
This leads to groove closure, accompanied by DNA bending toward the cationic
ligand. We explicitly treat the dynamic character of the cation-DNA interaction
using an adiabatic approximation, noting that DNA bending is much slower than the
diffusion of nonspecifically bound, mobile cations. We make semiquantitative
estimates of the free energy components of bending-electrostatic (with a
sigmoidal distance-dependent dielectric function), elastic, and entropic cation
localization-and find that the equilibrium state is bent B-DNA stabilized with a
self-localized cation. This is a bending polaron, formation of which should be
critically dependent on the strength of electrostatic interaction and the
concentration of highly mobile cations available for self-localization. We
predict that the resultant bend will be large (approximately 20-40 degrees),
smooth (because it is spread over 6 bp), and infrequent. The stability of such a
bend can be variable, from transient to highly stable (static) bending,
observable with standard curvature-measuring techniques. We further predict that
this bending mechanism will have an unusual sequence dependence: sequences with
less binding specificity will be more bent, unless the specific binding site is
in the major groove.
PMID- 9635769
TI - Tyrosine quenching of tryptophan phosphorescence in glyceraldehyde-3-phosphate
dehydrogenase from Bacillus stearothermophilus.
AB - Tyrosine is known to quench the phosphorescence of free tryptophan derivatives in
solution, but the interaction between tryptophan residues in proteins and
neighboring tyrosine side chains has not yet been demonstrated. This report
examines the potential role of Y283 in quenching the phosphorescence emission of
W310 of glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus
by comparing the phosphorescence characteristics of the wild-type enzyme to that
of appositely designed mutants in which either the second tryptophan residue,
W84, is replaced with phenylalanine or Y283 is replaced by valine.
Phosphorescence spectra and lifetimes in polyol/buffer low-temperature glasses
demonstrate that W310, in both wild-type and W84F (Trp84-->Phe) mutant proteins,
is already quenched in viscous low-temperature solutions, before the onset of
major structural fluctuations in the macromolecule, an anomalous quenching that
is abolished with the mutation Y283V (Tyr283-->Val). In buffer at ambient
temperature, the effect of replacing Y283 with valine on the phosphorescence of
W310 is to lengthen its lifetime from 50 micros to 2.5 ms, a 50-fold enhancement
that again emphasizes how W310 emission is dominated by the local interaction
with Y283. Tyr quenching of W310 exhibits a strong temperature dependence, with a
rate constant kq = 0.1 s(-1) at 140 K and 2 x 10(4) s(-1) at 293 K. Comparison
between thermal quenching profiles of the W84F mutant in solution and in the dry
state, where protein flexibility is drastically reduced, shows that the
activation energy of the quenching reaction is rather small, Ea < or = 0.17 kcal
mol(-1), and that, on the contrary, structural fluctuations play an important
role on the effectiveness of Tyr quenching. Various putative quenching mechanisms
are examined, and the conclusion, based on the present results as well as on the
phosphorescence characteristics of other protein systems, is that Tyr quenching
occurs through the formation of an excited-state triplet exciplex.
PMID- 9635770
TI - Secondary pair charge recombination in photosystem I under strongly reducing
conditions: temperature dependence and suggested mechanism.
AB - Photoinduced electron transfer in photosystem I (PS I) proceeds from the excited
primary electron donor P700 (a chlorophyll a dimer) via the primary acceptor A0
(chlorophyll a) and the secondary acceptor A1 (phylloquinone) to three [4Fe-4S]
clusters, Fx, FA, and FB. Prereduction of the iron-sulfur clusters blocks
electron transfer beyond A1. It has been shown previously that, under such
conditions, the secondary pair P700+A1- decays by charge recombination with t1/2
approximately 250 ns at room temperature, forming the P700 triplet state (3P700)
with a yield exceeding 85%. This reaction is unusual, as the secondary pair in
other photosynthetic reaction centers recombines much slower and forms directly
the singlet ground state rather than the triplet state of the primary donor. Here
we studied the temperature dependence of secondary pair recombination in PS I
from the cyanobacterium Synechococcus sp. PCC6803, which had been illuminated in
the presence of dithionite at pH 10 to reduce all three iron-sulfur clusters. The
reaction P700+A1- --> 3P700 was monitored by flash absorption spectroscopy. With
decreasing temperature, the recombination slowed down and the yield of 3P700
decreased. In the range between 303 K and 240 K, the recombination rates could be
described by the Arrhenius law with an activation energy of approximately 170
meV. Below 240 K, the temperature dependence became much weaker, and
recombination to the singlet ground state became the dominating process. To
explain the fast activated recombination to the P700 triplet state, we suggest a
mechanism involving efficient singlet to triplet spin evolution in the secondary
pair, thermally activated repopulation of the more closely spaced primary pair
P700+A0- in a triplet spin configuration, and subsequent fast recombination
(intrinsic rate on the order of 10(9) s(-1)) forming 3P700.
PMID- 9635771
TI - Properties of intramolecular proton transfer in carbonic anhydrase III.
AB - We investigated the efficiency of glutamic acid 64 and aspartic acid 64 as proton
donors to the zinc-bound hydroxide in a series of site-specific mutants of human
carbonic anhydrase III (HCA III). Rate constants for this intramolecular proton
transfer, a step in the catalyzed dehydration of bicarbonate, were determined
from the proton-transfer-dependent rates of release of H2 18O from the enzyme
measured by mass spectrometry. The free energy plots representing these rate
constants could be fit by the Marcus rate theory, resulting in an intrinsic
barrier for the proton transfer of deltaG0++ = 2.2 +/- 0.5 kcal/mol, and a work
function or thermodynamic contribution to the free energy of reaction wr = 10.8
+/- 0.1 kcal/mol. These values are very similar in magnitude to the Marcus
parameters describing intramolecular proton transfer from His64 and His67 to the
zinc-bound hydroxide in mutants of HCA III. That result and the equivalent
efficiency of Glu64 and Asp64 as proton donors in the catalysis by CA III
demonstrate a lack of specificity in proton transfer from these sites, which is
indirect evidence of a number of proton conduction pathways through different
structures of intervening water chains. The dominance of the thermodynamic
contribution or work function for all of these proton transfers is consistent
with the view that formation and breaking of hydrogen bonds in such water chains
is a limiting factor for proton translocation.
PMID- 9635772
TI - Site-specific thermodynamics and kinetics of a coiled-coil transition by spin
inversion transfer NMR.
AB - A 33-residue pseudo-wild-type GCN4 leucine zipper peptide is used to probe the
equilibrium conformational population in proteins. 13Calpha-NMR shows that chain
sites differ in structural content at a given temperature, and that two dimeric
folded forms are evident at many sites. Spin inversion transfer experiments are
reported bearing on the thermodynamics and kinetics of interconversion of the two
dimeric folded forms (Fa <--> Fb) at the 13Calpha-labeled position L13. At each
temperature, at conditions wherein the population of unfolded chains is quite
small, inversion of the Fa spins via a tuned Gaussian pi-pulse is followed by a
time interval (tau), interrogation, and recording of the free induction decay.
Fifteen such inversions, with varying tau, provide the time course for recovery
of equilibrium magnetization after inversion. Similar experiments follow
inversion of the Fb spins. Re-equilibration is known to be modulated by four
first-order rate constants: two (T1a(-1) and T1b(-1)) for spin-lattice relaxation
intrinsic to the respective sites, and two (kab and kba) for the conformational
change. All four follow from joint, Bayesian analysis of all the data at each
temperature. The equilibrium constant at each temperature for this local
transition, determined simply from the equilibrium relative magnetizations at Fa
and Fb sites, agrees well with the kinetic ratio kab/kba. The standard Gibbs
energies, enthalpy, and entropy follow. Activation parameters, both ways, are
accessible from the rate constants and suggest a transition state with high Gibbs
energy and enthalpy, but with entropy between those of Fa and Fb.
PMID- 9635773
TI - New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and
poly(ethylene glycol)-cholesterol conjugates.
AB - Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer
chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have
been newly synthesized and characterized. Their aggregation behavior in mixture
with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by
cryotransmission electron microscopy, high-performance gel exclusion
chromatography, and quasielastic light scattering. Nonaggregated, stable,
unilamellar vesicles were obtained at low polymer levels with optimal shape and
size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000
Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush
conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M
PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in
polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with
closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization
of the vesicles into disk-like structures of decreasing size with increasing PEG
content. This study underlines the bivalent role of M-PEG-Chol derivatives: while
behaving as solubilizing surfactants, they provide an efficient steric barrier,
preventing the vesicles from aggregation and fusion over a period of at least 2
weeks.
PMID- 9635774
TI - Fibrous long spacing collagen ultrastructure elucidated by atomic force
microscopy.
AB - Fibrous long spacing collagen (FLS) fibrils are collagen fibrils in which the
periodicity is clearly greater than the 67-nm periodicity of native collagen. FLS
fibrils were formed in vitro by the addition of alpha1-acid glycoprotein to an
acidified solution of monomeric collagen and were imaged with atomic force
microscopy. The fibrils formed were typically approximately 150 nm in diameter
and had a distinct banding pattern with a 250-nm periodicity. At higher
resolution, the mature FLS fibrils showed ultrastructure, both on the bands and
in the interband region, which appears as protofibrils aligned along the main
fibril axis. The alignment of protofibrils produced grooves along the main
fibril, which were 2 nm deep and 20 nm in width. Examination of the tips of FLS
fibrils suggests that they grow via the merging of protofibrils to the tip,
followed by the entanglement and, ultimately, the tight packing of protofibrils.
A comparison is made with native collagen in terms of structure and mechanism of
assembly.
PMID- 9635775
TI - Orientations of tyrosines 21 and 24 in coat subunits of Ff filamentous virus:
determination by Raman linear intensity difference spectroscopy and implications
for subunit packing.
AB - Virions of the Ff group of bacteriophages (fd, f1, M13) are morphologically
identical filaments (approximately 6-nm diameter x approximately 880-nm length)
in which a covalently closed, single-stranded DNA genome is sheathed by
approximately 2700 copies of a 50-residue alpha-helical subunit (pVIII).
Orientations of pVIII tyrosines (Tyr21 and Tyr24) with respect to the filament
axis have been determined by Raman linear intensity difference (RLID)
spectroscopy of flow-oriented mutant virions in which the tyrosines were
independently mutated to methionine. The results show that the twofold axis of
the phenolic ring (C1-C4 line) of Tyr21 is inclined at 39.5 +/- 1.4 degrees from
the virion axis, and that of Tyr24 is inclined at 43.7 +/- 0.6 degrees. The
orientation determined for the Tyr21 phenol ring is close to that of a structural
model previously proposed on the basis of fiber x-ray diffraction results
(Protein Data Bank, identification code 1IFJ). On the other hand, the orientation
determined for the Tyr24 phenol ring differs from the diffraction-based model by
a 40 degrees rotation about the Calpha-Cbeta bond. The RLID results also indicate
that each tyrosine mutation does not greatly affect the orientation of either the
remaining tyrosine or single tryptophan (Trp26) of pVIII. On the basis of these
results, a refined model is proposed for the coat protein structure in Ff.
PMID- 9635776
TI - Effects of temperature and deltaGo on electron transfer from cytochrome c2 to the
photosynthetic reaction center of the purple bacterium Rhodobacter sphaeroides.
AB - The kinetics of electron transfer from cytochrome c2 to the primary donor (P) of
the reaction center from the photosynthetic purple bacterium Rhodobacter
sphaeroides have been investigated by time-resolved absorption spectroscopy.
Rereduction of P+ induced by a laser pulse has been measured at temperatures from
300 K to 220 K in a series of specifically mutated reaction centers characterized
by altered midpoint redox potentials of P+/P varying from 410 mV to 765 mV (as
compared to 505 mV for wild type). Rate constants for first-order electron
donation within preformed reaction center-cytochrome c2 complexes and for the
bimolecular oxidation of free cytochrome c2 have been obtained by
multiexponential deconvolution of the kinetics. At all temperatures the rate of
the fastest intracomplex electron transfer increases by more than two orders of
magnitude as the driving force -deltaGo is varied over a range of 350 meV. The
temperature and deltaGo dependences of the rate constant fit the Marcus equation
well. Global analysis yields a reorganization energy lambda = 0.96 +/- 0.07 eV
and a set of electronic matrix elements, specific for each mutant, ranging from
1.2 10(-4) eV to 2.5 10(-4) eV. Analysis in terms of the Jortner equation
indicates that the best fit is obtained in the classical limit and restricts the
range of coupled vibrational modes to frequencies lower than approximately 200
cm(-1). An additional slower kinetic component of P+ reduction, attributed to
electron transfer from cyt c2 docked in a nonoptimal configuration of the
complex, displays a Marcus type dependence of the rate constant upon deltaGo,
characterized by a similar value of lambda (0.8 +/- 0.1 eV) and by an average
electronic matrix element smaller by more than one order of magnitude. In all of
the mutants, as the temperature is decreased below 260 K, both intracomplex
reactions are abruptly inhibited, their rate being negligible at 220 K. The free
energy dependence of the second-order rate constant for oxidation of cyt c2 in
solution suggests that the collisional reaction is partially diffusion
controlled, reaching the diffusion limit at exothermicities between 150 and 250
meV over the temperature range investigated.
PMID- 9635777
TI - Fatty acid-induced alteration of the porphyrin macrocycle of cytochrome P450 BM3.
AB - Surface-enhanced resonance Raman scattering (SERRS) of substrate-free and
substrate-bound forms of the P450 domain of cytochrome P450 BM3 are reported and
assigned. Substrate-free P450 yields mixed spin heme species in which the
pentacoordinate high-spin arrangement is dominant. The addition of laurate or
palmitate leads to an increase in high spin content and to an allosteric
activation of heme mode v29, which is sensitive to peripheral heme/protein
interactions. Differences between laurate and palmitate binding are observed in
the relative intensities of a number of bands and the splitting of the heme vinyl
modes. Laurate binding to P450 results in different protein environments being
experienced by each vinyl mode, whereas palmitate binding produces a smaller
difference. The results demonstrate the ability of SERRS to probe
substrate/prosthetic group interactions within an active site, at low protein
concentrations.
PMID- 9635778
TI - Resonance Raman microspectroscopy of myeloperoxidase and cytochrome b558 in human
neutrophilic granulocytes.
AB - With (resonance) Raman microscospectroscopy, it is possible to investigate the
chemical constitution of a very small volume (0.5 fl) in a living cell. We have
measured resonance Raman spectra in the cytoplasm of living normal,
myeloperoxidase (MPO)-deficient, and cytochrome b558-deficient neutrophils and in
isolated specific and azurophilic granule fractions, using an excitation
wavelength of 413.1 nm. Similar experiments were performed after reduction of the
redox centers by the addition of sodium dithionite. The specific and azurophilic
granules in both redox states appeared to have clearly distinguishable Raman
spectra when exciting at a wavelength of 413.1 nm. The azurophilic granules and
the cytochrome b558-deficient neutrophils showed Raman spectra similar to that of
the isolated MPO. The spectra of the specific granules and the MPO-deficient
neutrophils corresponded very well to published cytochrome b558 spectra. The
resonance Raman spectrum of the cytoplasmic region of normal neutrophilic
granulocytes could be fitted with a combination of the spectra of the specific
and azurophilic granules, which shows that the Raman signal of neutrophilic
granulocytes mainly originates from MPO and cytochrome b558, at an excitation
wavelength of 413.1 nm.
PMID- 9635779
TI - Atomic force microscopy detects changes in the interaction forces between GroEL
and substrate proteins.
AB - The structure of the Escherichia coli chaperonin GroEL has been investigated by
tapping-mode atomic force microscopy (AFM) under liquid. High-resolution images
can be obtained, which show the up-right position of GroEL adsorbed on mica with
the substrate-binding site on top. Because of this orientation, the interaction
between GroEL and two substrate proteins, citrate synthase from Saccharomyces
cerevisiae with a destabilizing Gly-->Ala mutation and RTEM beta-lactamase from
Escherichia coli with two Cys-->Ala mutations, could be studied by force
spectroscopy under different conditions. The results show that the interaction
force decreases in the presence of ATP (but not of ATPgammaS) and that the force
is smaller for native-like proteins than for the fully denatured ones. It also
demonstrates that the interaction energy with GroEL increases with increasing
molecular weight. By measuring the interaction force changes between the
chaperonin and the two different substrate proteins, we could specifically detect
GroEL conformational changes upon nucleotide binding.
PMID- 9635780
TI - Vesicle size distributions measured by flow field-flow fractionation coupled with
multiangle light scattering.
AB - The separation method, flow field-flow fractionation (flow FFF), is coupled on
line with multiangle laser light scattering (MALLS) for simultaneous measurement
of the size and concentration of vesicles eluting continuously from the
fractionator. These size and concentration data, gathered as a function of
elution time, may be used to construct both number- and mass-weighted vesicle
size distributions. Unlike most competing, noninvasive methods, this flow
FFF/MALLS technique enables measurement of vesicle size distributions without a
separate refractive index detector, calibration using particle size standards, or
prior assumptions about the shape of the size distribution. Experimentally
measured size distributions of vesicles formed by extrusion and detergent removal
are non-Gaussian and are fit well by the Weibull distribution. Flow FFF/MALLS
reveals that both the extrusion and detergent dialysis vesicle formation methods
can yield nearly size monodisperse populations with standard deviations of
approximately 8% about the mean diameter. In contrast to the rather low
resolution of dynamic light scattering in analyzing bimodal systems, flow
FFF/MALLS is shown to resolve vesicle subpopulations that differ by much less
than a factor of two in mean size.
PMID- 9635781
TI - Domain structure and molecular conformation in annexin V/1,2-dimyristoyl-sn
glycero-3-phosphate/Ca2+ aqueous monolayers: a Brewster angle microscopy/infrared
reflection-absorption spectroscopy study.
AB - Annexins comprise a family of proteins that exhibit a Ca2+-dependent binding to
phospholipid membranes that is possibly relevant to their in vivo function.
Although substantial structural information about the ternary
(protein/lipid/Ca2+) interaction in bulk phases has been derived from a variety
of techniques, little is known about the temporal and spatial organization of
ternary monolayer films. The effect of Ca2+ on the interactions between annexin V
(AxV) and anionic DMPA monolayers was therefore investigated using three
complementary approaches: surface pressure measurements, infrared reflection
absorption spectroscopy (IRRAS), and Brewster angle microscopy (BAM). In the
absence of Ca2+, the injection of AxV into an aqueous subphase beneath a DMPA
monolayer initially in a liquid expanded phase produced BAM images revealing
domains of protein presumably surrounded by liquid-expanded lipid. The protein
rich areas expanded with time, resulting in reduction of the area available to
the DMPA and, eventually, in the formation of condensed lipid domains in spatial
regions separate from the protein film. There was thus no evidence for a specific
binary AxV/lipid interaction. In contrast, injection of AxV/Ca2+ at a total Ca2+
concentration of 10 microM beneath a DMPA monolayer revealed no pure protein
domains, but rather the slow formation of pinhead structures. This was followed
by slow (>2 h) rigidification of the whole film accompanied by an increase in
surface pressure, and connection of solid domains to form a structure resembling
strings of pearls. These changes were characteristic of this specific ternary
interaction. Acyl chain conformational order of the DMPA, as measured by
nu(sym)CH2 near 2850 cm(-1), was increased in both the AxV/DMPA and AxV/DMPA/Ca2+
monolayers compared to either DMPA monolayers alone or in the presence of Ca2+.
The utility of the combined structural and temporal information derived from
these three complementary techniques for the study of monolayers in situ at the
air/water interface is evident from this work.
PMID- 9635782
TI - Passive mechanical behavior of human neutrophils: effects of colchicine and
paclitaxel.
AB - The role of microtubules in determining the mechanical rigidity of neutrophils
was assessed. Neutrophils were treated with colchicine to disrupt microtubules,
or with paclitaxel to promote formation of microtubules. Paclitaxel caused an
increase in the number of microtubules in the cells as assessed by
immunofluorescence, but it had no effect on the presence or organization of actin
filaments or on cellular mechanical properties. Colchicine at concentrations <1.0
microM caused disruption of microtubular structures, but had little effect on
either F-actin or on cellular mechanical properties. Higher concentrations of
colchicine disrupted microtubular structure, but also caused increased actin
polymerization and increases in cell rigidity. Treatment with 10 microM
colchicine increased F-actin content by 17%, the characteristic cellular
viscosity by 30%, the dependence of viscosity on shear rate by 10%, and the
cortical tension by 18%. At 100 microM colchicine the corresponding increases
were F-actin, 25%; characteristic viscosity, 50%; dependence of viscosity on
shear rate, 20%; and cortical tension, 21%. These results indicate that
microtubules have little influence on the mechanical properties of neutrophils,
and that increases in cellular rigidity caused by high concentrations of
colchicine are due to a secondary effect that triggers actin polymerization. This
study supports the conclusion that actin filaments are the primary structural
determinants of neutrophil mechanical properties.
PMID- 9635783
TI - Flow resistance and drag forces due to multiple adherent leukocytes in
postcapillary vessels.
AB - Computational fluid dynamics was used to model flow past multiple adherent
leukocytes in postcapillary size vessels. A finite-element package was used to
solve the Navier-Stokes equations for low Reynolds number flow of a Newtonian
fluid past spheres adhering to the wall of a cylindrical vessel. We determined
the effects of sphere number, relative geometry, and spacing on the flow
resistance in the vessel and the fluid flow drag force acting to sweep the sphere
off the vessel wall. The computations show that when adherent leukocytes are
aligned on the same side of the vessel, the drag force on each of the interacting
leukocytes is less than the drag force on an isolated adherent leukocyte and can
decrease by up to 50%. The magnitude of the reduction depends on the ratio of
leukocyte to blood vessel diameter and distance between adherent leukocytes.
However, there is an increase in the drag force when leukocytes adhere to
opposite sides of the vessel wall. The increase in resistance generated by
adherent leukocytes in vessels of various sizes is calculated from the
computational results. The resistance increases with decreasing vessel size and
is most pronounced when leukocytes adhere to opposite sides of the vessel.
PMID- 9635784
TI - Diffusion coefficients in the lateral intercellular spaces of Madin-Darby canine
kidney cell epithelium determined with caged compounds.
AB - The diffusion coefficients of two caged fluorescent dyes were measured in free
solution and in the lateral intercellular spaces (LIS) of cultured Madin-Darby
canine kidney (MDCK) cells after photoactivation by illumination with a
continuous or pulsed UV laser. Both quantitative video imaging and a new
photometric method were utilized to determine the rates of diffusion of the caged
fluorescent dyes: 8-((4,5-dimethoxy-2-nitrobenzyl)oxy)pyrene-1,3,6-trisulfonic
acid (DMNB-HPTS) and (4,5-dimethoxy-2-nitrobenzyl) fluorescein dextran (10,000
MW) (DMNB-caged fluorescein dextran). The diffusion coefficients at 37 degrees C
in free solution were 3.3 x 10(-6) cm2/s (HPTS) and 0.98 x 10(-6) cm2/s (10,000
MW dextran). Diffusion of HPTS within nominally linear stretches of the LIS of
MDCK cells grown on glass coverslips was indistinguishable from that in free
solution, whereas dextran showed a 1.6 +/- 0.5-fold reduction in diffusivity.
Measurements of HPTS diffusion within the LIS of multicellular regions also
exhibited a diffusivity comparable to the free solution value. The restriction to
diffusion of the dextran within the LIS may be due to molecular hindrance.
PMID- 9635785
TI - Reinnervation after nerve suture in rat groin flaps.
AB - Regeneration of sensory and adrenergic nerves in the skin was studied in rats.
The aim was to investigate the effect of reanastomosing the cut nerve ends of the
nerve trunk leading to the microvascular groin flap. Reinnervation was
demonstrated immunohistochemically using calcitonin gene-related peptide (CGRP)
as marker for sensory nerves, neuropeptide Y (NPY) and tyrosine hydroxylase (TH)
as markers for adrenergic nerves and Protein Gene Product 9.5 (PGP 9.5) as
general neuronal marker. It was demonstrated that reanastomosing of the nerve
trunk was favourable for both the sensory and sympathetic reinnervation of
microsurgical flaps.
PMID- 9635786
TI - New technique of complete thymectomy in adult rats without tracheal intubation.
AB - Adult rat thymectomy is frequently performed as part of the protocol for
experiments in transplant immunology. Current methods used are either imprecise
(suction methods) or require tracheal intubation (surgical technique) and are
thus difficult to master. We have developed a safe technique of surgical removal
of the thymus with resolution of any pneumothorax by suction through the xyphoid
insertions of the diaphragm. This method is easy to learn and gives a 95% success
rate.
PMID- 9635787
TI - Nerve regeneration in diabetic rats.
AB - This study evaluated the capacity of diabetic rats to recover the ability to walk
after nerve repair or nerve graft of the posterior tibial nerve at thigh level.
Functional recovery of the posterior tibial nerve was evaluated by walking track
analysis during regeneration in streptozotocin-induced diabetic rats. Surgical
procedures were performed 8 weeks after induction of diabetes. The nerve repair
was epineurial. The nerve graft was a 1.5 cm segment orthotopically replaced.
There was no significant difference in functional recovery between normal and
diabetic rats for both the nerve repair and nerve graft groups at 6, 12, and 24
weeks after nerve reconstruction. It is concluded that the presence of diabetes
is not a contraindication for nerve reconstruction.
PMID- 9635788
TI - Technical details for safer venous and biliary anastomoses for liver
transplantation in the rat.
AB - Although orthotopic liver transplantation in the rat is a well-established
experimental model, no detailed illustrated description of the procedure is
available in the literature. As a result, achieving success in the technique
without prolonged learning time requires training in specialized centers where
the step-by-step details essential to success in the technique can be learnt. The
aim of this paper is to provide beginners with the culminative experience of 15
years of improvements made to Kamada's original model, clearly illustrating the
necessary steps and fine detail of each anastomosis to help beginners avoid
unnecessary complications. We hope that this complete description of orthotopic
liver transplantation in the rat, which remains the most difficult rodent
transplant model to master, will greatly help microsurgeons acquire this
demanding procedure.
PMID- 9635789
TI - Developing a standardized test for the assessment of suturing skill in novice
microsurgeons.
AB - Suturing performance was assessed for 13 novice microsurgeons throughout a 4-5
day microsurgical training course. Time to complete a suture (from needle
insertion to completion of tie-off) was assessed on a standardized suture task,
for two sutures at the beginning and end of each training day. For days 2-4,
suturing performance with actual tissue was also assessed at both the beginning
and end of each day. An average learning curve for suturing performance on the
standardized test was developed and demonstrated huge performance improvement. A
consistent and significant relationship existed between trainees' performance on
the standardized suturing test and suturing of actual tissue. Thus the
standardized test appears both to reflect actual suturing performance and to be
sensitive to improvements in suturing skill that result from practice.
PMID- 9635790
TI - Do leukocytes contribute to impaired microvascular tissue perfusion after
arterial repair?
AB - Impaired capillary perfusion may result in flap failure. Platelet emboli,
polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as
possible causes. This study investigates the role of PMNs in causing impaired
capillary perfusion in a free flap model. PMN concentrations were depleted using
antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were
isolated on a single neurovascular pedicle and after a simulated technically poor
arterial anastomosis upstream and reperfusion, capillary perfusion was measured
each hour for 6 hours. Even though the number of PMNs was significantly reduced
in the animals treated with antineutrophil serum, capillary perfusion was not
changed compared with controls. These results demonstrate that depleting
circulating PMNs does not protect capillary perfusion in our model. These
findings suggest that reduced capillary perfusion downstream from an anastomotic
repair is not mediated by the presence of PMNs in the microcirculation.
PMID- 9635791
TI - A comparison by burst testing of three types of vascular anastomosis.
AB - A new in vivo test for burst strength of arterial anastomoses was tested in 40
rats. Twelve had a severed right femoral artery reanastomosed by the traditional
nine-suture technique. In a second group of 12, a modified telescoping sleeve
method of reanastomosis was used. In a third group of 12, a laser-assisted
anastomosis using four stay sutures was performed. Four rats had sham procedures.
Immediately after reanastomosis three vessels from each group plus all four sham
surgical vessels were subjected to burst testing. These tests were performed
again on the repaired vessels at 1 week, 1 month, and 2 months. All the vessels
were patent at burst testing. All repairs held at all times to greater than 160
mm mean arterial pressure. The four-suture telescopic anastomosis technique was
consistently strongest over time, but all techniques showed adequate strength at
all time intervals.
PMID- 9635792
TI - A simple method of lower extremity arteriography in the rat.
PMID- 9635793
TI - Functional recovery of transected nerves treated with systemic BDNF and CNTF.
AB - The purpose of this study was to investigate the effect of systemic co-injections
of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor
(BDNF) on the functional recovery of transected sciatic nerves repaired by
epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley
rats underwent transection of their sciatic nerves and repair by either EC or CT.
With each repair technique, systemic injections of neurotrophic factors or
control injections of lactated Ringer's solution were given. This resulted in
four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function
was assessed using sciatic functional indices (SFI). Animals whose nerves were
repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P =
0.04) all had better functional recovery than those whose nerves were repaired by
EC. There were no significant differences among these three groups, however.
Animals in the CT group manifested the most rapid rate of recovery (P = 0.02
compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF
improve the rate and extent of sciatic functional recovery after nerve repair.
The improvement in recovery conferred is not additive.
PMID- 9635794
TI - Surgical technique for vascularized ear transplantation in mice.
AB - Traditionally, the mouse nonvascularized skin graft has been widely used in organ
transplant research. There are, however, several limitations with this model, the
main one being the different immune response of vascularized vs. nonvascularized
grafts. We have recently developed a vascularized, orthotopic ear transplant
model in mice. This model has several advantages that make it a useful tool to
study many aspects of transplantation. The donor operation consists of harvesting
the ear with intact arterial and venous pedicles. The arterial pedicle is
dissected down to the common carotid artery with ligation of all branches except
the auricular artery. The venous pedicle is based on the jugular vein with
preservation of the auricular veins draining into the posterior facial vein. In
the subsequent recipient operation, the graft is transplanted into an orthotopic
position using the common carotid artery for arterial inflow and the jugular vein
for venous outflow. We performed 16 such transplants (6 isografts, 5 allografts,
and 5 xenografts), with a success rate of 94% (15/16). The donor operation time
was 1.5 hours and the recipient operation time was 2.5 hours. The total time for
anastamosis was 45 +/- 5 minutes. Serial biopsies were obtained on days 3, 5, and
7, and correlated with gross findings. In summary, this study illustrates that it
is technically possible to transplant a mouse ear graft. The main advantage of
this model is that it is a vascularized graft that can be visibly observed and
easily biopsied, thus allowing for good correlation between gross and
histological findings after transplantation. We plan to use this model further to
study in detail the rejection patterns in an allograft and xenograft setting.
PMID- 9635796
TI - Laser nerve repair by solid protein band technique. I: identification of optimal
laser dose, power, and solder surface area.
AB - Thirty-four tibial nerves in 17 adult male wistar rats were repaired by applying
protein bands longitudinally across the nerve join. The bands were then
irradiated with a fibre-coupled diode laser (lambda = 810 nm). The relations
among the laser weld breaking force, the power, and the solder surface area were
investigated, while maintaining a consistent ratio between the total mass of
protein solder in a band and total laser energy delivered (the laser energy
dose). When this laser energy dose was held constant, the average breaking force
of the laser welds irradiated by 72 mW laser output power was weaker than that
reached after 90 mW laser radiation. There is a linear relation between the
solder breaking force and the solder surface area when band thickness, laser
power, and laser dose are unvaried.
PMID- 9635795
TI - Evans blue dye modifies the ultrastructure of normal and regenerating arterial
endothelium in rats.
AB - Evans blue dye (EBD) identifies areas of increased vascular permeability, which
is usually indicative of endothelial damage. Most studies examine EBD-stained
areas light-microscopically, but others analyze the cells with the electron
microscope. Electron microscopic studies have assumed that EBD itself did not
change the ultrastructure of endothelial cells and this hypothesis was tested in
the following study. The left iliac arteries of 20 rats were injured with 1-mm
vascular clamps for 5 minutes. At 7 and 14 days after clamping, 10 rats for each
time were infused intravenously either with normal-saline or EBD, perfused 30
minutes later with fixatives. Then the clamp-injured arteries, contralateral
(unclamped) arteries, aortae, and the aortic bifurcations were removed for EM
morphometry. In an additional (control) group of 10 rats, with no clamp injuries,
5 were infused with EBD and 5 with normal-saline and all 10 rats were perfused 30
minutes later, as above. EBD caused a significant simplification of the
junctional morphology in both normal and regenerating endothelium. It also
increased the area fractions of cytoplasmic vesicles in regenerating endothelium.
These data demonstrate that EBD causes measurable ultrastructural changes in
normal and regenerating endothelium. This effect should be taken into account
when using EBD to assess various insults to blood vessels.
PMID- 9635797
TI - Laser nerve repair by solid protein band technique. II: assessment of long-term
nerve regeneration.
AB - A total of 18 adult male Wistar rats had left tibial nerve repaired by either the
laser-solder technique or a more conventional microsuture technique. The diode
laser power was 90 mW and the radiation dose 16 J/mg. Three months
postoperatively electrophysiology showed that the average compound muscle action
potential (CMAP) of the laser repair group was not significantly different from
the CMAP of the sutured nerves. Light microscopy confirmed regeneration of
myelinated axons in both groups of animals. The laser-solder technique, when used
with such parameters, proved to be a reliable method to achieve satisfactory
peripheral nerve anastomosis and nerve regeneration.
PMID- 9635798
TI - Cystic tumours of the pancreas.
PMID- 9635799
TI - Skull radiographs and children with blunt head injury.
PMID- 9635800
TI - Antibiotic prophylaxis in the initial management of severe acute pancreatitis.
AB - BACKGROUND: The role of antibiotic prophylaxis in the initial management of
patients with acute pancreatitis is an area of major controversy. Contrary to
earlier clinical trials, recent experimental and clinical studies have accrued
evidence that warrants reappraisal of current clinical practice. This article
reviews these recent advances in knowledge. METHODS: All papers derived from a
Medline search for the years 1990-1997 inclusive using the text words 'acute',
'pancreatitis', 'antibiotic' and 'antibiotics' were studied. Additional papers
were derived from reference lists within papers identified by the Medline search.
Only experimental and clinical papers relevant to the issue of prophylactic
antibiotic therapy in acute pancreatitis are included in the review. RESULTS AND
CONCLUSION: Current experimental evidence favours the use of prophylactic
antibiotics in severe acute pancreatitis. The results of contemporary randomized
clinical trials restricted to patients with prognostically severe acute
pancreatitis have demonstrated improvement in outcome associated with antibiotic
treatment.
PMID- 9635801
TI - Diagnosis and treatment of sphincter of Oddi dysfunction.
AB - BACKGROUND Sphincter of Oddi dysfunction is a challenge from both the diagnostic
and therapeutic point of view. There is much ongoing debate about the accuracy
and usefulness of various diagnostic tests, as there is about the effectiveness
of proposed therapeutic alternatives. METHODS: A comprehensive review of the past
15 years' literature was undertaken, using the Medline database and cross
referencing of major articles on the subject. RESULTS AND CONCLUSION: Endoscopic
and surgical treatments result in similar outcomes, with considerable failure
rates. The latter reflect the difficulties in accurate diagnosis and a lack of
sound objective criteria for selecting patients for intervention. In addition, in
some patients sphincter of Oddi dysfunction may be only part of a generalized
motility disorder of the gastrointestinal tract.
PMID- 9635802
TI - Recent advances in the surgical treatment of faecal incontinence.
AB - BACKGROUND: Improved imaging and refined technology have led to a number of
recent advances in the surgical treatment of faecal incontinence. METHODS:
Original articles, identified using a computer database (Medline), and recently
published abstracts of meetings were selected on the basis of greatest clinical
relevance; these were reviewed. RESULTS: Ultrasonographic characterization has
led to improved therapeutic strategies. Simple structural damage is readily
identified and external sphincter repair results in a good outcome for a majority
of patients. For more complex structural damage, or for the newly recognized
primary internal sphincter degeneration, alternative treatment strategies are
emerging. The electrically stimulated gracilis neosphincter and the artificial
bowel sphincter offer good results. The latter may be a more simple operation.
For structurally intact but weak sphincters, sacral nerve stimulation is a
promising therapy. Other therapies, such as antegrade irrigation, may be helpful
for patients with neurological disorders. CONCLUSION: Better imaging, refined
classification and new operations are leading to improved surgical techniques for
faecal incontinence.
PMID- 9635803
TI - Simple laparoscopic gastropexy as the initial treatment of paraoesophageal hiatal
hernia.
AB - BACKGROUND: Paraoesophageal hiatal hernia is relatively rare compared with
sliding hernia but it is associated with serious complications. Its clinical
management presents a major challenge since many patients are elderly and unfit
for a formal repair. This paper describes a laparoscopic method aimed at reducing
the complications of open repair. METHODS: Thirteen patients treated for
symptomatic paraoesophageal hernia were included in the study. Eleven patients
successfully underwent a simple laparoscopic modification of the Boerema anterior
gastropexy. Two patients required an open anterior gastropexy through a
minilaparotomy because of incomplete reduction of the hernia. A five-puncture
technique was used. The stomach and any other contents of the sac were reduced
into the abdomen and the stomach was firmly fixed to the fascia of the anterior
abdominal wall with GORE-TEX sutures tied extracorporeally. RESULTS: There was
one postoperative death due to spontaneous intrathoracic perforation of the
posterior aspect of the stomach in an elderly woman with severe cardiac disease.
There was no postoperative morbidity. Eight of the ten patients who went home
following laparoscopic gastropexy have remained asymptomatic on follow-up. In
three patients, two in the laparoscopic group and one in the open group, symptoms
recurred. CONCLUSION: While anterior gastropexy has a significant incidence of
recurrent herniation, the clinical results of this simple procedure in a high
risk population support its use as the initial surgical option.
PMID- 9635804
TI - Pancreatic cancer resection in elderly patients.
AB - BACKGROUND: Pancreatic cancer resection is considered a high-risk procedure in
patients aged 70 years or older. METHODS: Some 398 patients with pancreatic
adenocarcinoma, observed between 1990 and 1995, were reviewed. Operative outcome
and survival of 33 patients aged 70 years or more were compared with findings in
85 younger patients who underwent resection. RESULTS: Resectability was not
significantly different between the elderly and younger patients; neither were
mortality or overall morbidity. However, patients aged 70 years or more had more
relaparotomies (P < 0.01) and more haemorrhagic complications (P < 0.001).
Nutritional recovery after resection was satisfying even for elderly patients
(body-weight gain and increase in serum albumin concentrations, P < 0.05).
Univariate analysis showed a moderately poorer survival in the elderly (P =
0.09). Multivariate analysis demonstrated that tumour diameter, grading and Union
Internacional Contra la Cancrum stage were independent prognostic factors,
whereas age was not. CONCLUSION: Patients aged 70 years or more can benefit from
pancreatic cancer resection similarly to younger patients.
PMID- 9635805
TI - Survival following pancreaticoduodenectomy with resection of the superior
mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head.
AB - BACKGROUND: The survival of patients who underwent pancreaticoduodenectomy with
or without en bloc resection of the superior mesenteric-portal vein (SMPV)
confluence for adenocarcinoma of the pancreatic head was compared. METHODS: To be
considered for surgery, patients were required to fulfil the following computed
tomography criteria for resectability: (1) absence of extrapancreatic disease,
(2) no evidence of tumour extension to the superior mesenteric artery (SMA) or
coeliac axis, and (3) a patent SMPV confluence. Tumour adherence to the superior
mesenteric vein (SMV) or SMPV confluence was assessed at operation and en bloc
venous resection was performed when necessary to achieve complete tumour
extirpation. RESULTS: Seventy-five consecutive patients underwent
pancreaticoduodenectomy, 44 without venous resection and 31 with en bloc
resection of the SMPV confluence. There were no perioperative deaths in either
group; late (more than 6 months) occlusion of the reconstructed SMPV confluence
contributed to the death of two patients. Median survival in the 31 patients who
required venous resection at the time of pancreaticoduodenectomy was 22 months,
and that for the 44 control patients was 20 months (P = 0.25). CONCLUSION:
Patients with adenocarcinoma of the pancreatic head who require venous resection
during pancreaticoduodenectomy for isolated tumour extension to the SMV or SMPV
confluence (in the absence of tumour extension to the SMA or coeliac axis) have a
duration of survival no different from that of patients who undergo standard
pancreaticoduodenectomy. These data suggest that venous involvement is a function
of tumour location rather than an indicator of aggressive tumour biology.
PMID- 9635806
TI - Experimental study of a novel phospholipase A2 inhibitor in acute pancreatitis.
AB - BACKGROUND: In acute pancreatitis, two different types of secretory phospholipase
A2 (PLA2) have been found: pancreatic type I PLA2 and non-pancreatic type II
PLA2. In this study a potent new PLA2 inhibitor effective against type II PLA2
was used in an experimental model of acute pancreatitis. METHODS: In 70 rats the
efficacy of the compound was analysed in two experimental models of acute
pancreatitis: cerulein- and taurocholate-induced acute pancreatitis, imitating
mild and severe disease respectively. Serum rat type I PLA2 protein concentration
and type I and type II PLA2 catalytic activities were measured while giving the
inhibitor therapeutically. In a prophylactic protocol the effect on histology was
analysed. RESULTS: In the taurocholate model, type II PLA2 activity was found to
be nine-fold higher than in the cerulein model (P < 0.002), whereas the activity
of type I PLA2 was not increased. The inhibitor significantly decreased serum
type II PLA2 activity in the taurocholate model of acute pancreatitis (P < 0.05)
but type I PLA2 protein concentration and type I PLA2 activity were not affected.
The inhibitor also reduced histological tissue damage, with significant
differences at 3 and 12 h (P < 0.01). CONCLUSION: The PLA2 inhibitor
significantly reduced type II PLA2 activity and was able to protect the pancreas
against tissue damage. PLA2 inhibition offers the possibility of a treatment for
acute pancreatitis.
PMID- 9635807
TI - Laparoscopic cholangiography: a prospective study.
AB - BACKGROUND: The place of cholangiography has been controversial in the
conventional and now in the laparoscopic setting. The aim of this study was to
evaluate laparoscopic cholangiography and compare use of a portable C-arm image
intensifier with conventional radiography. METHODS: One hundred and ninety-seven
consecutive patients undergoing laparoscopic cholecystectomy were randomized
before operation to cholangiography by either C-arm image intensifier or
conventional radiography. Data were collected on a pro forma completed
immediately after the operation. RESULTS: Cholangiography was successful in 93.0
per cent of patients. Cholangiography with an image intensifier was significantly
faster. In 19 patients the ductal system was obscured by a cannula; in 17 of
these cases a metal cannula was used. In 31.6 per cent of patients the clip on
the cystic duct was within 1 cm or less of the common bile duct (CBD).
CONCLUSION: Laparoscopic cholangiography is a safe procedure. Use of an image
intensifier should be the preferred method of obtaining images. Metal cannulas
are more likely to obscure the ductal system. The proximity of the clip on the
cystic duct to the CBD highlights the potential for injury caused by
electrocautery or erroneous clip application.
PMID- 9635808
TI - Multidisciplinary approach to biliary complications of laparoscopic
cholecystectomy.
AB - BACKGROUND: Bile leaks and bile duct strictures are major complications of
cholecystectomy which increased in incidence after the introduction of
laparoscopic surgery. The management and outcome of these complications following
the introduction of laparoscopic cholecystectomy was reviewed. METHODS: Eighteen
patients of median age 45 (range 22-70) years were treated between January 1992
and December 1995. Six patients had a common hepatic duct (CHD) stricture, four
following a failed previous repair. Nine patients had bile leaks from bile duct
transection (four), cystic stump (four) or segment V duct (one). Two patients had
partial bile duct damage with primary sutured repair at time of cholecystectomy.
One patient had recurrent haemobilia from a hepatic artery pseudoaneurysm.
RESULTS: Cystic stump or segment V leaks were treated successfully by endoscopic
stenting (median follow-up 42 months). Roux loop biliary reconstruction was
carried out in nine patients: two CHD strictures, three of the four failed
primary CHD repairs and four bile duct transections. All had normal liver
function test results at median follow-up of 30 months. The two patients with
partial duct injuries repaired at initial surgery required no further
intervention. The right hepatic artery aneurysm was successfully embolized. There
have been no deaths or major complications of endoscopic, radiological or
surgical intervention. CONCLUSION: Endoscopic stenting successfully treats cystic
stump and segment V duct leaks. Duct strictures, including failed initial repairs
and transections, have a good outcome with Roux-en-Y loop reconstruction.
PMID- 9635809
TI - Mortality following elective infrarenal aortic reconstruction: a Joint Vascular
Research Group study.
AB - BACKGROUND: This study aimed to define the cause of death in patients undergoing
elective infrarenal aortic reconstruction. METHODS: Members of the Joint Vascular
Research Group who had collected details prospectively of patients undergoing
elective aortic reconstruction provided information on those who died. RESULTS:
Details of 3786 patients were obtained. Some 171 patients died (133 following
abdominal aortic aneurysm (AAA) and 38 after aortofemoral bifurcation graft
(AFBG) for occlusive disease). The mortality rate following AAA repair was 4.8
per cent, rising to 16 per cent if repair was combined with either renal or
distal reconstruction (P < 0.001). Similar results were obtained with AFBG (3.4
and 11 per cent respectively, P < 0.001). The first major complication
encountered was cardiac (39.8 per cent), followed by bleeding (20.5 per cent),
respiratory (13.5), and gut (5.3 per cent), or limb ischaemia (6.4 per cent).
Bleeding was commoner following reconstruction for aneurysm compared with that
for occlusive disease (P < 0.05). Eighty-six patients (50.3 per cent) died from
the first major complication. Of the remainder, 45 (53 per cent) developed
multisystem organ failure (MSOF). The most commonly involved systems were
cardiac, respiratory and renal. CONCLUSION: Cardiac problems were the major cause
of death following infrarenal aortic reconstruction. MSOF is the 'final common
pathway' in about half of the patients who survive the initial complication.
PMID- 9635810
TI - Survey of changes in the provision of vascular surgical services in the Oxford
Region over 5 years.
AB - AIM: This study aimed to examine changes in the provision of vascular services in
the Oxford region over 5 years. METHODS: A questionnaire was sent to all general
surgeons in the region asking of their involvement in vascular surgery. Data were
obtained from the Department of Health concerning vascular procedures and
inpatient codes for each district in the Oxford Region from 1990-1991 to 1994
1995. Office of Population Censuses and Surveys (OPCS) data for abdominal aortic
aneurysm repair and femoral artery reconstruction were validated against data
collected prospectively for West Berkshire. RESULTS: Eighteen of 45 surgeons who
replied to the questionnaire carried out elective and emergency arterial work.
All were members of the Vascular Surgical Society of Great Britain and Ireland
(VSS). All but one took part in the general surgical rota. Eight surgeons carried
out emergency arterial surgery only; only two of these were members of the VSS.
Of 19 surgeons undertaking no arterial surgery, 15 operated on primary and 11 on
recurrent varicose veins. The number of arterial reconstructions rose from 20.8
per 100000 population to 28 per 100000 throughout the study. The greatest
increase occurred in districts where a new vascular consultant had been
appointed. Similar results were obtained with endovascular procedures. The number
of major amputations remained fairly constant at approximately 11 per 100000
population. The number of inpatient episodes for arterial disease also rose, from
35.7 to 47.6 per 100000. In validating OPCS codes against prospectively collected
data, discrepancies for individual years were noted but the annual trend was
reflected fairly accurately by the codes. CONCLUSION: There has been an increase
in vascular activity in the region, but variations still exist between different
districts.
PMID- 9635811
TI - Role of magnetic resonance angiography for assessment of abdominal aortic
aneurysm before endoluminal repair.
AB - BACKGROUND: A detailed knowledge of the morphology of the aorta and iliac
arteries is an important prerequisite for successful endoluminal abdominal aortic
aneurysm (AAA) repair. The best method of preoperative evaluation remains to be
determined. METHODS: A prospective study was undertaken between January 1994 and
July 1995 to assess the ability of computed tomography (CT), magnetic resonance
angiography (MRA), colour duplex imaging and intra-arterial digital subtraction
angiography (IA-DSA) to visualize AAA morphology. RESULTS: Eighty-two consecutive
patients (64 men, 18 women) with AAA were assessed with MRA, contrast-enhanced
CT, colour duplex imaging and IA-DSA. Median age was 74 (range 59-87) years and
median AAA diameter was 5.7 (range 3.5-9.7) cm. Five patients were unable to
tolerate CT or MRA examination. Seventy-seven patients underwent both CT and MRA.
Of these, 55 also had a colour duplex scan and 32 underwent arteriography. The
scans were assessed by an independent blinded observer. MRA was significantly
better (P < 0.01) at visualizing AAA morphology compared with CT and colour
duplex imaging. There was no statistically significant difference between MRA and
arteriography. CONCLUSION: MRA is useful in patient selection for endoluminal AAA
repair, as it avoids use of iodinated contrast medium and ionizing radiation.
PMID- 9635812
TI - A 21-year experience of abdominal aortic aneurysm operations in Edinburgh.
AB - BACKGROUND: This study reviews the results of infrarenal abdominal aortic
aneurysm (AAA) surgery over 21 years (1 January 1976 to 31 December 1996).
METHODS: A prospectively gathered database was analysed. RESULTS: Infrarenal AAA
repair was performed in 1515 patients: 492 (32.5 per cent) had elective repair of
an asymptomatic AAA; 194 (12.8 per cent) had elective repair of a symptomatic
AAA; 156 (10.3 per cent) had emergency repair of a symptomatic non-ruptured AAA;
and 673 (44.4 per cent) had surgery for a ruptured AAA. The 30-day and/or same
admission mortality rates were 6.1, 5.8, 14.1 and 37 per cent respectively.
Operative mortality increased in all four groups over the study interval,
although this only attained statistical significance in patients having elective
repair of a symptomatic, non-ruptured AAA. There was a significant increase in
the age of patients undergoing elective repair of an asymptomatic AAA, but not in
the other three groups. There was also a significant increase in the proportion
of straight 'tube' grafts inserted in all four groups. CONCLUSIONS: It remains
the minority of patients who have elective operation before the onset of symptoms
and/or rupture. Despite anaesthetic and surgical specialization, the results of
AAA repair have not improved over the past two decades. Operative mortality may
be increasing, possibly because of the increasing age and associated comorbidity
of the patients presenting to this unit.
PMID- 9635814
TI - Arteriovenous fistula using transposed basilic vein.
AB - BACKGROUND: Patients who need long-term haemodialysis often require multiple
operations to maintain their vascular access. The options for secondary or
tertiary access procedures may become increasingly limited. Prosthetic conduits
are commonly used in difficult cases but are associated with a high incidence of
complications. METHODS: The brachial artery-transposed basilic vein arteriovenous
fistula has been used in preference to a prosthetic graft on 31 occasions.
RESULTS: There were no technical failures and 28 of these fistulas matured. No
major infective complications occurred. CONCLUSION: This procedure should be
considered before resorting to a prosthetic graft for vascular access.
PMID- 9635813
TI - Population-based record linkage study of the incidence of abdominal aortic
aneurysm in Western Australia in 1985-1994.
AB - BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) has increased
steadily during the past 30 years. METHODS: Trends in the incidence and surgical
intervention for AAA in Western Australia were reviewed for the interval 1985
1994. A population-based health database was used to link morbidity and mortality
records of all patients aged 55 years or more who died from rupture or were
admitted and treated surgically for AAA. Three groups were separated for
analysis: patients with a ruptured AAA, those admitted for elective repair and
those admitted as an emergency with an acute (non-ruptured) aneurysm. RESULTS:
There was a decline in the incidence of both emergency and elective procedures
for AAA after 1992. While the mortality rate from ruptured AAA has also fallen
since 1991, the overall case fatality rate for ruptured AAA has fallen by only
1.3 per cent (from 80.7 to 79.3 per cent). CONCLUSION: The decline in mortality
rate and emergency procedures may result from a fall in the incidence of ruptured
AAA, due to an increasing rate of elective surgery before 1992. The decline in
elective procedures from 1992 may be due to a fall in the prevalence of AAA owing
to high rates of elective surgery, or to a fall in the incidence of the disease
itself.
PMID- 9635815
TI - Multimodality treatment in the control of deep musculoaponeurotic fibromatosis.
AB - BACKGROUND: Deep musculoaponeurotic fibromatoses are rare soft tissue neoplasms
with a propensity for local recurrence. METHODS: A retrospective analysis was
carried out of the factors contributing to local disease control in 75 patients
treated between 1963 and 1993. RESULTS: Multivariate analysis identified the type
of surgical excision (P < 0.001) and involvement of pathological resection
margins (P < 0.02) as significant factors contributing to local recurrence. After
a median follow up of 47 months (range 24 months to 29 years) 31 (49 per cent) of
the 63 patients who had an 'adequate' surgical resection developed local
recurrence. The median time before development of local recurrence was 83.4
(range 8-129) months in patients with clear pathological resection margins. This
was significantly shortened to 13.1 (range 2-35) months in those with positive
margins (P < 0.001). CONCLUSION: Adequate surgical extirpation is the most
important determinant in local disease control. Treatment of local recurrence
ranged from observation during periods of disease stabilization to multimodality
treatment for aggressive disease.
PMID- 9635816
TI - Anovestibular fistula to Bartholin's gland.
AB - BACKGROUND: Acquired fistulation from the anal canal to Bartholin's gland has not
been reported before. This fistula has been identified in 11 women treated
between 1991 and 1995. METHODS: All discharge diagnoses during this period were
searched. The clinical records of patients managed for this diagnosis were
reviewed. RESULTS: Eleven women aged 24-49 years were identified. Seven of 11
fistulas arose in association with inflammatory bowel disease (five Crohn's
disease, two ulcerative colitis). Patients typically presented with the vulval
passage of flatus and faeces or acute sepsis of Bartholin's gland. Time to
diagnosis of the fistula ranged from 1 to 15 (median 8) months after the onset of
symptoms. Anatomically, all fistulas were high trans-sphincteric or
suprasphincteric. All eight fistulas for which repair was attempted (five in the
presence of inflammatory bowel disease) remain healed at short-term follow-up.
Proctocolectomy was undertaken in two patients with severe Crohn's colitis.
CONCLUSION: Ano-Bartholin's fistulas, although rare in general surgical practice,
present with troublesome symptoms and may be repaired successfully.
Gynaecologists and surgeons should be aware of this clinical entity to avoid
unnecessary delays in treatment.
PMID- 9635817
TI - Outcome following laparoscopic resection for colorectal cancer.
AB - BACKGROUND: A prospective comparison of laparoscopic or laparoscopically assisted
colorectal resection versus open resection has been undertaken to evaluate early
benefits and cost implications. METHODS: Consecutive patients with colorectal
cancer underwent either elective laparoscopic (n = 25) or open (n = 29)
resection. RESULTS: Mean hospital stay was significantly shorter in the
laparoscopic group: 10.7 versus 17.8 days. Mean morphine requirements were less
in patients who had laparoscopic resection and their recovery, as measured by the
dynamometer hand grip and the SF-36 symptom score, was more rapid. Adequate
tumour clearance was achieved in the laparoscopic group. In both groups, the
number of lymph nodes harvested was similar. Port-site or wound recurrence has
not been observed at a median follow-up of 28 months. CONCLUSION: When
laparoscopic colorectal resection is possible, there are significant early
benefits for patients.
PMID- 9635818
TI - Surgical treatment of severe duodenal polyposis in familial adenomatous
polyposis.
AB - BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at risk for
adenomas and cancers in the duodenum but the ideal management of duodenal
polyposis remains uncertain. METHODS: The outcome of surgical resection was
analysed in 18 patients with FAP who had severe duodenal polyposis. RESULTS:
Duodenotomy and clearance of duodenal adenomas was performed seven times in six
patients. There were two duodenal leaks and, after a mean follow-up of 53 (range
36-72) months, duodenal adenomas recurred in all patients and five had severe
polyposis. Pancreatoduodenectomy was performed in seven patients with severe
duodenal polyposis. Histology of the specimens revealed two unsuspected duodenal
carcinomas at an early stage. After a mean follow-up of 42 months all patients
were alive and well, and there was no case of jejunal polyposis.
Pancreatoduodenectomy was attempted in five patients with duodenal cancer and
only one survived more than 4 years. CONCLUSION: Surgical excision of duodenal
adenomas should be discussed before carcinoma occurs. Surgical polypectomy fails
to guarantee a polyp-free duodenum and carries a risk of postoperative
complications whereas pancreatoduodenectomy eliminates the risk of duodenal
cancer with an acceptable morbidity rate. Pancreatoduodenectomy could be offered
to some patients with large or multiple villous duodenal adenomas repeatedly
showing severe dysplasia.
PMID- 9635819
TI - Assessment of a scoring system for breast imaging.
AB - BACKGROUND: Triple assessment is the standard method of assessing symptomatic
breast lumps. There is an accepted format for reporting cytology but not for the
reporting of mammograms or breast ultrasonographic images. This study describes a
scoring system for reporting breast imaging methods. METHODS: Patients with
symptomatic breast lumps seen during 1 year were included. All patients underwent
triple assessment. Imaging studies were reported using a grading system from 1 to
5. The results of triple assessment were compared with the final histology.
RESULTS: Some 127 women had both mammography and ultrasonographic imaging; the
final grade was identical in 60 per cent. The positive predictive value of
imaging reported as grade 5 or 4 combined with cytology of C5 or C4 was 100 per
cent. All lesions with C3 cytology and benign imaging were benign on histological
examination whereas if a C3 grade was combined with imaging grade 5 or 4, all the
lesions were malignant. CONCLUSION: Combining the imaging grade with the results
of aspiration cytology and clinical examination often predicts the final
histology in patients with breast disease.
PMID- 9635821
TI - Experimental study of acid burden and acute oesophagitis.
AB - BACKGROUND: The relationship of the pH of oesophageal refluxate and its pepsin
content to injury of oesophageal mucosa remains unclear. A study was made of the
earliest morphological alterations in the oesophageal mucosa secondary to varying
concentrations of hydrochloric acid with or without pepsin. METHODS: Adult cats
had varying concentrations of acid with and without 1 per cent porcine pepsin
infused into the oesophagus through a paediatric feeding tube placed 5 cm above
the oesophagogastric junction at a rate of 1 ml/min for 30 min. At autopsy 24 h
later, the oesophagus was removed intact and scored by an expanded modification
of a previously published histopathological scoring system. This included
estimates of the intensity and distribution of four morphological features: basal
cell hyperplasia (BCH), intraepithelial leucocytes (IELs), subepithelial
leucocytes and ulcers. Each of these four categories was scored from 0 to 4, with
a maximum injury score of 16. RESULTS: Mean(s.e.m.) scores were as follows: pH 1,
15.0(1.0); pH 1 with pepsin, 13.3(1.4); pH 2, 15.3(0.7); pH 2 with pepsin,
11.7(1.1); pH 3, 1.8(1.6); pH 3 with pepsin, 3.7(1.9); pH 4 with or without
pepsin, 0.6(0.2). Differences between pH 3 and 4 versus pH 1 and 2 were
significant (P < 0.05). CONCLUSION: Injury to the oesophagus is more dependent on
the pH of refluxate than on the presence of pepsin. Peptic injury appears to
occur at a critical threshold of acid burden (pH < 3) as opposed to a graded
level of injury based on a pH scale.
PMID- 9635820
TI - Effect of graft reperfusion on intracellular calcium levels in mononuclear
leucocytes during human orthotopic liver transplantation.
AB - BACKGROUND: Orthotopic liver transplantation (OLT) is accompanied by local and
systemic manifestations of the ischaemia-reperfusion syndrome. Local effects are
mediated in part through changes in intracellular calcium levels in Kupffer
cells. Arachidonic acid metabolites mediate increases in intracellular calcium
concentration and thus potentiate the effect of free radicals. This study was
carried out to characterize white blood cell (WBC) calcium changes as a mediator
for white cell activation in human OLT. METHODS: Twenty consecutive patients had
OLT using standard surgery and anaesthesia techniques. Blood samples were drawn
for estimation of WBC cytosolic calcium content at induction of anaesthesia, 5
min before graft reperfusion and 15 min after reperfusion. The rate of rise in
intracellular calcium concentration after the addition of a calcium chloride 1
mmol L(-1) solution to the extracellular milieu was used as an estimate of
membrane calcium permeability. RESULTS: Both extracellular (P = 0.0002) and
intracellular (P = 0.0008) calcium concentrations rose with time. However, at no
time was there a correlation between extracellular and intracellular calcium
levels or rate of calcium influx (r2 = 0.002, P = 0.78). There was a significant
increase in intracellular calcium concentration (P = 0.0008) and in the rate of
rise of intracellular calcium levels (P = 0.0009) after reperfusion. CONCLUSION:
There was a significant increase in circulating monocyte membrane permeability
for calcium and cytosolic calcium concentration following reperfusion in human
OLT. This was independent of extracellular calcium concentration. These results
are consistent with WBC activation by reperfusion and could be implicated in the
systemic reperfusion syndrome seen in OLT in humans.
PMID- 9635822
TI - Association between restriction fragment length polymorphism of the L-myc gene
and susceptibility to gastric cancer.
AB - BACKGROUND: L-myc polymorphism has been documented to be a representative genetic
trait which is related an individual's susceptibility to several cancers.
However, there have been no reports concerning any significant association
between susceptibility to gastric cancer and L-myc polymorphism. METHODS: The
distribution of L-myc polymorphism in 61 patients with gastric cancer was
determined by polymerase chain reaction-based restriction fragment length
polymorphism and compared with that of 107 healthy control subjects. RESULTS:
There was a significant difference in the distribution of both genotypes (P =
0.024) and allele frequencies (P = 0.026) between the two groups. The relative
risk of gastric cancer for genotypes with the shorter (S) allele was 3.09
compared with the longer (L) allele homozygote. No significant correlation with
clinicopathological features of the cancers except for prognosis was found. The
patients with SS genotypes had a worse prognosis than those with LL or LS
genotypes (P = 0.029). CONCLUSION: L-myc polymorphism may be significant in an
individual's susceptibility to gastric cancer in Japan, and may be a useful
marker for identifying patients at high risk of developing gastric cancer.
PMID- 9635823
TI - Enteral nutrition is superior to parenteral nutrition in severe acute
pancreatitis: results of a randomized prospective trial.
PMID- 9635824
TI - Randomized controlled trial of open and closed haemorrhoidectomy.
PMID- 9635825
TI - Comparison of endoanal magnetic resonance imaging with surgical findings in
perirectal sepsis.
PMID- 9635826
TI - Health economics and quality of life in cancer trials: report based on a UKCCCR
workshop. United Kingdom Coordinating Committee on Cancer Research.
PMID- 9635827
TI - Alteration of oestradiol metabolism in myc oncogene-transfected mouse mammary
epithelial cells.
AB - Targeted overexpression of the c-myc oncogene induces neoplastic transformation
in immortalized, non-tumorigenic mouse mammary epithelial cells (MMEC).
Experiments in the present study were conducted to examine whether cellular
transformation induced by c-myc oncogene is associated with altered metabolism of
17beta-oestradiol (E2). The parental, MMEC and the stable c-myc transfectant
(MMEC/myc3) cell lines were compared for major oestrogen metabolic pathways,
namely E2 and E1 interconversion, and C2- and C16alpha-hydroxylation by both high
pressure liquid chromatography (HPLC) analysis and the 3H release assay using
specifically labelled [C2-3H]E2 or [C16alpha-3H]E2. The reductive conversion of
E1 to E2 was about 14-fold and 12-fold higher than the oxidative conversion of E2
to E1 in MMEC and MMEC/myc3 cells respectively. However, in MMEC/myc3 cells, both
reductive and oxidative reactions were decreased by about 32% and 12% relative to
those seen in the parental MMEC cells (P = 0.0028). The extent of C16alpha
hydroxylation was increased by 164.3% (P < 0.001), with a concomitant 48.4%
decrease (P < 0.001) in C2-hydroxylation in MMEC/myc3 cells; this resulted in a
fourfold increase in the C16alpha/C2 hydroxylation ratio in this cell line. Thus,
a persistent c-myc expression, leading to aberrant hyperproliferation in vitro
and tumorigenesis in vivo, is associated with an altered oestrogen metabolism.
However, it remains unclear whether this represents a result of oncogene
expression/activation or is rather a consequence of phenotypic transformation of
the cells.
PMID- 9635828
TI - Temperature sensitivity of human wild-type and mutant p53 proteins expressed in
vivo.
AB - p53 is activated in response to DNA damage and functions in the maintenance of
genetic integrity. Loss of p53 function because of mutation of the p53 gene is
associated with over half all human cancers. Certain human p53 mutants are
conformationally flexible in vitro and are temperature sensitive, with partial or
complete recovery of wild-type (wt) properties at 32 degrees C. We have now
tested the functional capacities of selected p53 mutants in vivo, by transfection
into established human cell lines. Unexpectedly, we found that wt p53 can be
temperature sensitive for transactivation of a co-transfected target gene in
vivo. Flexible mutants retained varying degrees of functional capacity in
transfected cells, and the recipient cell line appeared to be a significant
determinant of both wt and mutant p53 function; importantly, two p53 null cell
lines commonly used to study p53 function (Saos-2 and Hep3B) differed markedly in
this latter respect. We also show that the p53 mutant V272M, which exhibits
sequence-specific DNA binding in vitro, is nonetheless defective for
transactivation and is unable to induce apoptosis in vivo. The valine 272 residue
may thus be crucial for properties (other than sequence-specific DNA binding)
that are important for p53 function(s) in vivo.
PMID- 9635829
TI - Expression of p53, Bcl-2 and Bax in cisplatin-induced apoptosis in testicular
germ cell tumour cell lines.
AB - We examined the sensitivity for cisplatin-induced apoptosis in a panel of four
testicular germ cell tumour (TGCT) cell lines and monitored the cellular
expression of the apoptosis-related proteins p53, Bcl-2 and Bax. Three of four
TGCT cell lines (NT2, NCCIT and S2) were hypersensitive for cisplatin-induced
apoptosis, while the TGCT cell line 2102 EP appeared to be resistant for
cisplatin-induced apoptosis, even at relatively high drug concentrations (12.5
microM). For all four cell lines, the induction of apoptosis by cisplatin
correlated with drug sensitivity in the MTT assay. The differences in
chemosensitivity and induction of apoptosis could not be attributed to
differences in cellular platinum accumulation, DNA platination or platinum-DNA
adduct removal. We next analysed the relationship between p53 status and
cisplatin-induced up-regulation of p53, and the susceptibility to cisplatin
induced apoptosis. Wild-type p53 containing NT2 and 2102 EP cells showed p53 up
regulation upon drug treatment, and NCCIT (mutant p53) and S2 (no p53 protein)
cells did not. Consistently, the increase in wild-type p53 protein in NT2 and
2102 EP cells led to an increase in mRNA level of the p53 downstream gene
p21/WAF/CIP, whereas mutant p53-containing NCCIT cells and p53-non-expressing S2
cells could not transactivate this p53-responsive gene. As NT2, NCCIT and S2 were
readily triggered into apoptosis, while 2102 EP cells failed to undergo cisplatin
induced apoptosis, our data suggest that the presence of wild-type and/or
transactivation-competent p53 might not be an absolute prerequisite for efficient
induction of apoptosis in TGCT cell lines. Also endogenous levels of Bcl-2 and
Bax expression did not correlate with cisplatin-induced apoptosis. In addition,
the endogenous Bcl-2 and Bax expression was not affected by cisplatin treatment.
The present study suggests that, at least in our panel of TGCT cell lines,
hypersensitivity for cisplatin-induced apoptosis might not be necessarily
correlated with the presence of wild-type p53 and is probably not associated with
Bcl-2 and Bax expression.
PMID- 9635830
TI - p53 mutations in non-small-cell lung cancers occurring in individuals without a
past history of active smoking.
AB - Accumulating evidence suggests that the p53 gene is a good target for molecular
epidemiological studies. We previously reported an association between the
presence of p53 mutations and lifetime cigarette consumption. Although over 675
p53 mutations have been reported in lung cancers in the literature thus far, very
little is known about the nature of such changes in lung cancers in the absence
of a smoking background. In the present study, we therefore analysed 69 non-small
cell lung cancer specimens from individuals without any history of active smoking
and identified p53 mutations in 26% of the cases. Statistical analysis of the
present cohort of non-smokers also showed absence of significant relationship
between p53 mutations and age, sex, histological type or disease stage.
Comparison of mutational spectra between the present results in non-smokers and
previously reported mutations in smokers clearly demonstrated G:C to T:A
transversions to be significantly less frequent in non-smokers than in smokers
(OR 5.35, 95% CI 1.77-16.12). Interestingly, G:C to C:G and G:C to A:T mutations
were also observed in tumours of non-smokers at similar frequencies to G:C to T:A
mutations, suggesting that these mutations can occur relatively frequently in the
absence of active smoking. This study is, to our knowledge, the largest so far
analysing a well-defined cohort of non-smokers in a single laboratory.
PMID- 9635831
TI - Analysis of p53, p16MTS, p21WAF1 and H-ras in archived bladder tumours from
workers exposed to aromatic amines.
AB - Exposure to aromatic amines is considered a major risk factor for the development
of bladder cancer. In this study, we have analysed the pattern of point mutations
in several tumour genes in 21 cases of bladder cancer arising among western
European workers exposed to aromatic amines in an attempt to determine whether
this exposure may be associated with a unique spectrum of mutations. Of the four
genes analysed (p53, p16MTS1, p21WAF1 and H-ras), only p53 showed a high
frequency of mutations (in 8 out of 21 cases, 38%). Two mutations were found in
p16, one in H-ras and none in p21 exon 3. All mutations were at G:C base pairs,
mostly at non-CpG residues. This spectrum of mutations, which is highly
suggestive of an involvement of exogenous carcinogens, is however identical to
the spectrum of p53 mutations detected in bladder cancers of the general
population. In exposed workers, p53 mutations were associated with tumour grade
and with high occupational and tobacco exposure. Taken together, our data suggest
that the same carcinogens may be responsible for the development of bladder
cancers in workers exposed to aromatic amines and in the general population.
PMID- 9635832
TI - Cytotoxicity of weak electrolytes after the adaptation of cells to low pH: role
of the transmembrane pH gradient.
AB - Theory suggests that the transmembrane pH gradient may be a major determinant of
the distribution of lipophilic weak electrolytes across the cell membrane. The
present study evaluates the extent to which this factor contributes to pH
dependent changes in the cytotoxicity of two such chemotherapeutic drugs:
chlorambucil and mitoxantrone. Experiments were performed with two cell types of
the same origin but exhibiting different pH gradients at the same extracellular
pH (pHe): CHO cells cultured under normal physiological conditions (pH 7.4) and
acid-adapted cells obtained by culturing under low pH conditions (6.8). Over the
pHe range examined (6.0-7.6), the difference between intracellular pH (pHi) and
pHe increased with decreasing pHe. Acid-adapted cells were more resistant to
acute changes in pHi than normal cells, resulting in substantially larger
gradients in these cells. Drug cell survival curves were performed at pHe values
of 6.4, 6.8 and 7.4. The cytotoxicity of chlorambucil, a weak acid, increased
with decreasing pHe, and low pH-adapted cells were more sensitive than normal
cells at the same pHe. In contrast, for the weak base, mitoxantrone, cytotoxicity
increased with pHe and was more pronounced in normal cells. As predicted by the
theory, the cytotoxicity of both drugs changed exponentially as a function of the
pH gradient, regardless of cell type. For mitoxantrone, the rate of such change
in cytotoxicity with the gradient was approximately two times greater than for
chlorambucil. This difference is probably due to the presence of two equally
ionizable crucial groups on mitoxantrone vs one group on chlorambucil. It is
concluded that the cellular pH gradient plays a major role in the pH-dependent
modulation of cytotoxicity in these weak electrolytes. The data obtained also
suggest that a pronounced differential cytotoxicity may be expected in vivo in
tumour vs normal tissue. In comparison with normal cells at a pHe of 7.4 (a model
of cells in normal tissues), acid-adapted cells at a pHe of 6.8 (a model of cells
distal from supplying blood vessels in tumours) were more sensitive to
chlorambucil, with a dose-modifying factor of approximately 6, and were more
resistant to mitoxantrone by a factor of 14.
PMID- 9635833
TI - Increased plasminogen binding is associated with metastatic breast cancer cells:
differential expression of plasminogen binding proteins.
AB - Overexpression of urokinase-type plasminogen activator and its receptor
correlates with metastatic capacity in breast cancer. In this study we show that
the urokinase/urokinase receptor-overexpressing, metastatic human breast cancer
cell line MDA-MB-231 (1) bound significantly more cell-surface plasminogen in a
lysine-dependent manner and (2) was capable of generating large amounts of
plasmin compared with the non-metastatic cell lines MCF-7 and T-47D. In addition,
distinct plasminogen binding proteins were detected in the plasma membranes of
the cell lines, suggesting heterogeneity of binding proteins. Plasminogen binding
was analysed using a combination of dual-colour fluorescence flow cytometry and
ligand histochemistry (for comparative and cellular localization of ligand
binding), and fluorimetry (for Scatchard analysis). Apart from revealing the
greater plasminogen binding capacity of MDA-MB-231 cells, flow cytometry and
histochemistry also revealed that, in all three cell lines, non-viable or
permeabilized cells bound significantly more plasminogen in a lysine-dependent
manner than viable or non-permeabilized cells. Viable MDA-MB-231 cells bound
plasminogen with moderate affinity and high capacity (Kd = 1.8 microM, receptor
sites per cell 5.0 x 10(7). Our results indicate that differences in cell surface
specific plasminogen binding capacity between cell lines may not be detectable
with binding techniques that cannot distinguish between viable and non-viable
cells.
PMID- 9635834
TI - In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell
low-grade non-Hodgkin's lymphoma.
AB - The flux of calcium forms an important intracellular messenger system. The bcl-2
oncoprotein is thought to make cells resistant to a variety of insults, including
cytotoxic drugs, by the suppression of apoptosis, which appears to involve the
repartitioning of intracellular calcium. Three drugs that affect calcium pathways
and may influence this repartitioning, i.e. dantrolene, azumolene (a water
soluble dantrolene analogue) and nimodipine, were studied in cell culture, using
both a transformed follicle centre lymphoma cell line and primary culture of
lymphoma cells in vitro in a manner that resulted in a growth pattern closely
resembling that of the malignancy in vivo. Dantrolene and azumolene were potent
inducers of cell death in both systems reducing the viable cell count by 70-90%
in comparison with normal controls. Nimodipine, in comparison, appeared to have
no significant effect. These results obtained in an in vitro setting suggest that
further evaluation of dantrolene and azumolene for the treatment of low-grade non
Hodgkin's lymphoma is warranted.
PMID- 9635835
TI - Allelic imbalance and instability of microsatellite loci on chromosome 1p in
human non-small-cell lung cancer.
AB - The mapping of allelic loss on the short arm of chromosome 1 has been performed
in non-small-cell lung cancer. We used a set of 11 microsatellite loci spanning
1p to examine the frequency of allelic imbalance in a panel of 58 tumours. Fifty
one of 58 (87.9%) cases have shown somatic allelic loss at one or more loci
tested. The two shortest regions of the overlap (SRO) of the deletions have been
identified: SRO 1 at 1p13.1 and SRO 2 at 1p32-pter. Allelic losses at these
regions have been compared among adenocarcinoma and squamous cell carcinoma and
no difference has been found. In contrast to SRO 1, deletions at SRO 2
significantly correlated with advanced stage of the disease as well as post
operative metastasizing and relapse. These data may suggest that SRO 1 and SRO 2
can harbour tumour-supressor genes (TSGs) involved in different stages of NSCLC
development. SRO 2 is still quite large and its refined mapping should help
attempts to clone and identify the putative TSG(s). Microsatellite instability
(replication errors) affecting only 6 (10.3%) of 58 tumour samples is an
infrequent genetic alteration at the loci tested.
PMID- 9635836
TI - Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells
but not to 'normal' rat astrocytes.
AB - This study compares the effect of gamma-linolenic acid (GLA) and its precursor
linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and
'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes.
By contrast, LA supplementation did not affect the survival of either cell types.
There were minor differences in the uptake, distribution and use of radiolabelled
GLA and LA by the 36B10 cells and astrocytes. GLA and LA supplementation
increased the total polyunsaturated fatty acid (PUFA) content of the cells
indicating increased oxidative potential. However, elevated levels of 8
isoprostane, an indicator of increased oxidative stress, were only observed in
the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA
enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the
radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox
blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did
not affect the radiation response of either cell type. While cyclo-oxygenase
inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation
response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not
affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic
astrocytoma cells but not to normal astrocytes.
PMID- 9635837
TI - The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic
therapy in bladder cancer cells in vitro.
AB - Photodynamic therapy (PDT) is a cancer treatment based on the interaction of
light and a photosensitizing chemical. The photosensitizer protoporphyrin IX
(PpIX) is generated via the haem biosynthetic pathway after administration of
aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic
and acidotic relative to normal tissue, which may influence PpIX generation and
compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA
at various oxygen tensions and H+ ion concentrations, and assessed the effects on
PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19
mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15,
0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1)
respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a
result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production
was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at
pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was
enhanced at lower pH values. These results suggest that ALA-induced PDT may be
inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may
slightly enhance the efficacy of ALA-induced PDT.
PMID- 9635838
TI - Absence of stimulation of poly(ADP-ribose) polymerase activity in patients
predisposed to colon cancer.
AB - Poly(ADP-ribose)polymerase (PARP) has been implicated in DNA repair mechanisms
and the associated activity shown to markedly increase after DNA damage in
carcinogen-treated cells. A defective DNA repair has been associated to the
aetiology of human cancers. In order to assess the potential role of this enzyme
in cellular response to DNA damage by gamma-radiation, we studied the activity of
PARP in patients with familial adenomatous polyposis (FAP). We compared poly(ADP
ribose)polymerase activity by the rate of incorporation of radioactivity from
[3H]adenine-NAD+ into acid-insoluble material in permeabilized leucocytes from
FAP patients and healthy volunteers. Concomitantly, the intracellular levels of
NAD+--the substrate for the PARP--and the reduced counterpart NADH were
determined using an enzymatic cycling assay 30 min after [60Co] gamma-ray cells
irradiation. Our results demonstrate that a marked stimulation of PARP activity
is produced upon radiation of the cells from healthy subjects but not in the FAP
leucocytes, which concomitantly show a marked decrease in total NAD-/NADH
content. Our observations point to a role of PARP in the repair of the gamma
radiation-induced DNA lesions through a mechanism that is impaired in the cells
from FAP patients genetically predisposed to colon cancer. The differences
observed in PARP activation by gamma-radiation in patients and healthy
individuals could reflect the importance of PARP activity dependent on treatment
with gamma-rays. The absence of this response in FAP patients would seem to
suggest a possible defect in the role of PARP in radiation-induced DNA repair in
this cancer-prone disease.
PMID- 9635839
TI - Telomerase activity in 144 brain tumours.
AB - Unlimited proliferation in immortalized cells is believed to be highly dependent
on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric
repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric
repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99
benign and 45 malignant brain tumours. The TRAP assay results were quantitated by
normalizing the telomerase activity of each specimen to that of human glioma cell
line T98G to obtain the relative telomerase activity. Telomerase activity was
also assessed visually from the autoradiograms as being positive or negative. One
hundred and sixteen tumours with negative telomerase activity had null relative
telomerase activity, whereas 28 tumours with positive telomerase activity had
relative telomerase activities of 12-84.3% (mean 0% vs 36.1 +/- 19.3%, P <
0.0001). Thus, quantification of telomerase activity confirmed the results of the
visual evaluation of telomerase activity on autoradiograms. Based on the
assessment, malignant brain tumours had a higher positive rate of telomerase
activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that
positive telomerase activity is strongly associated with malignant brain tumours
and is rather rare in benign tumours, such as neurinomas or meningiomas.
PMID- 9635840
TI - Semi-quantitation of urokinase plasminogen activator and its receptor in breast
carcinomas by immunocytochemistry.
AB - Urokinase plasminogen activator (uPA) is a serine protease involved in cancer
invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known
as uPAR. In this study, uPA and uPAR levels were semiquantitated by
immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD
UK 1, uPA was detected both in stromal and in malignant cells. However, the
predominant location was in the stromal cells. Using double-staining, cells
containing uPA were also found to coexpress either cytokeratin (an epithelial
cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With
monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle- or
macrophage-like stromal cells, especially when these cells surrounded invasive
breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was
not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA
levels in both stromal and epithelial cells were significantly correlated with
those for uPAR. We conclude that both uPA and its receptor are mostly present in
stromal cells in invasive breast carcinomas. These results suggest that stromal
cells collaborate with malignant cells to mediate metastasis.
PMID- 9635841
TI - Mutation analysis of the c-mos proto-oncogene in human ovarian teratomas.
AB - Female transgenic mice lacking a functional c-mos proto-oncogene develop ovarian
teratomas, indicating that c-mos may behave as a tumour-suppressor gene for this
type of tumour. We have analysed the entire coding region of the c-MOS gene in a
series of human ovarian teratomas to determine whether there are any cancer
causing alterations. DNA from twenty teratomas was analysed by single-strand
conformational analysis (SSCA) and heteroduplex analysis (HA) to screen for
somatic and germline mutations. In nine of these tumours the entire gene was also
sequenced. A previously reported polymorphism and a single new sequence variant
were identified, neither of which we would predict to be disease-causing
alterations. These results suggest that mutations in the coding region of the c
MOS gene do not play a significant role in the genesis of human ovarian
teratomas.
PMID- 9635842
TI - Reduced cellular accumulation of topotecan: a novel mechanism of resistance in a
human ovarian cancer cell line.
AB - In order to unravel possible mechanisms of clinical resistance to topoisomerase I
inhibitors, we developed a topotecan-resistant human IGROV-1 ovarian cancer cell
line, denoted IGROV(T100r), by stepwise increased exposure to topotecan (TPT).
The IGROV(T100r) cell line was 29-fold resistant to TPT and strongly cross
resistant to SN-38 (51-fold). However, the IGROV(T100r) showed only threefold
resistance to camptothecin (CPT). Remarkably, this cell line was 32-fold
resistant to mitoxantrone, whereas no significant cross-resistance against other
cytostatic drugs was observed. No differences in topoisomerase I protein levels
and catalytic activity as well as topoisomerase I cleavable complex stabilization
by CPT in the IGROV-1 and IGROV(T100r) cell lines were observed, indicating that
resistance in the IGROV(T100r) cell line was not related to topoisomerase I
related changes. However, resistance in the resistant IGROV(T100r) cell line to
TPT and SN-38 was accompanied by decreased accumulation of the drugs to
approximately 15% and 36% of that obtained in IGROV-1 respectively. No reduced
accumulation was observed for CPT. Notably, accumulation of TPT in the IGROV-1
cell line decreased under energy-deprived conditions, whereas the accumulation in
the IGROV(T100r) cell line increased under these energy-deprived conditions. The
efflux of TPT at 37 degrees C was very rapid in the IGROV-1 as well as the
IGROV(T100r) cell line, resulting in 90% efflux within 20 min. Importantly, the
efflux rates of TPT in the IGROV-1 and IGROV(T100r) cell lines were not
significantly different and were shown to be independent on P-glycoprotein (P-gp)
or multidrug resistance-associated protein (MRP). These results strongly suggest
that the resistance of the IGROV(T100r) cell line to TPT and SN-38 is mainly
caused by reduced accumulation. The reduced accumulation appears to be mediated
by a novel mechanism, probably related to impaired energy-dependent uptake of
these topoisomerase I drugs.
PMID- 9635843
TI - Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to
endocrine therapy.
AB - Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2
were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40
untreated primary or early recurrent breast tumours. Significant associations
were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P <
0.04) status. After disease recurrence, patients were treated with assessable
courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary
disease were consequently found to be predictive of endocrine responsiveness in
the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However,
despite these associations, a number of pLIV1- and/or pS2-positive tumours failed
to respond to therapy.
PMID- 9635844
TI - The effect of 3-week tamoxifen treatment on oestrogen receptor levels in primary
breast tumours: a flow cytometric study.
AB - The effect of 3-week, preoperative tamoxifen treatment on oestrogen receptor (ER)
levels, expressed by primary breast tumours, was examined. Patients (age-matched)
with breast cancer, confirmed by fine-needle aspiration, were either treated with
20 mg ml(-1) oral tamoxifen per day or received no medication in the 3-week
interval between assessment and surgery. Quantification of ER using flow
cytometry was performed on the surgically removed tumour samples from tamoxifen
treated (n = 40) and control (n = 38, untreated) patient groups. The tumours were
mechanically disaggregated, and saponin treatment rendered these cells permeable
to antibodies. Using dual-parameter labelling with a FITC-conjugated antibody
(NCL-5D3) directed against cytokeratin 8/18/19 and a biotinylated antibody (DAKO
ER 1D5) directed against the oestrogen receptor, ER quantification was determined
on a number of receptors per cell basis. Using QC quantum bead standards, ER
levels in the epithelial cell population, the non-epithelial cell population and
the whole-cell population (ER+) were calculated. ER levels were significantly
lower in the total cell population than tamoxifen-treated patients (P = 0.002)
when compared with the control (untreated) group. By using a gating procedure
using 5D3 antibody positivity, a significantly lower level was detected on
examining the cytokeratin-positive population alone (P = 0.006). Using a
complementary gating technique, ER levels were quantified in the cytokeratin
negative cell population. Examination of this group of cells showed no
significant difference between the levels of oestrogen receptor found in the
tamoxifen-treated and untreated groups (P = 0.4). We have demonstrated that ER
levels can be monitored by flow cytometry. ER levels in patients treated with
tamoxifen 3 weeks before operation are significantly lower than in a comparative
group of patients who received no drug. Furthermore, the most significant
difference in receptor levels is seen by quantification of total ER levels
expressed by all the tissue.
PMID- 9635845
TI - Tissue carcinoembryonic antigen and oestrogen receptor status in breast
carcinoma: an immunohistochemical study of clinical outcome in a series of 252
patients with long-term follow-up.
AB - Carcinoembryonic antigen (CEA) is a well-known tumour marker whose
immunohistochemical expression could be prognostically relevant in breast
carcinomas. We evaluated CEA immunohistochemical expression, using the specific
T84.66 monoclonal antibody, in a series of 252 consecutive cases of infiltrating
breast carcinomas (104 N0, 148 N1/2) with median follow-up of 84 months.
Oestrogen receptor (ER) status has been evaluated with the immunohistochemical
method (ER1D5 antibody, 10% cut-off value): 121 cases were ER negative, 128 cases
were ER positive and in three cases ER status was unknown. CEA staining was
cytoplasmic; staining intensity and percentage of reacting cells were combined to
obtain a final score (CEA score). The difference between the distribution of CEA
score within the modalities of the other variables was not statistically
significant. Univariate survival analysis has been performed on the series of
node-negative and node-positive patients. In the latter subgroup, this has been
performed separately for patients treated with systemic adjuvant hormonal therapy
or chemotherapy. A multivariate analysis was only performed for node-positive
patients treated with adjuvant therapy. CEA immunoreactivity was not
prognostically relevant in any subset of analysed patients. The most important
prognostic markers were nodal status and tumour size.
PMID- 9635846
TI - Plasma insulin-like growth factor in primary breast cancer patients treated with
adjuvant chemotherapy.
AB - Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer
patients undergoing six courses of adjuvant chemotherapy. The only observed
variation was a slight decrease (10%) in IGF-1 concentrations, assayed before
treatment, between the first and the second courses of chemotherapy. During
chemotherapy courses, there were no statistically significant variations in IGF
1. These results suggest that chemotherapy, unlike the specific hormonal
treatments tamoxifen and somatostatin, certainly does not act via a decrease in
plasma IGF-1.
PMID- 9635847
TI - High-dose therapy including carboplatin adjusted for renal function in patients
with relapsed or refractory germ cell tumour: outcome and prognostic factors.
AB - Thirty-one consecutive patients with relapsed or refractory GCT received an HDT
schedule including carboplatin, the dose of which was adjusted to measured
glomerular filtration rate. There was one HDT-associated death (3%), due to acute
renal failure. The 3-year probability of overall and disease-free survival for 21
patients with primary refractory disease or responsive relapse was 60% and 42%,
respectively, while none of ten patients with refractory relapse have survived
disease free.
PMID- 9635848
TI - Cisplatin dose rate as a risk factor for nephrotoxicity in children.
AB - The purpose of the study was to evaluate the incidence, risk factors and changes
in severity with time of cisplatin nephrotoxicity in children. A total of 35
children underwent measurement of glomerular filtration rate (GFR) and tubular
function after completion of cisplatin chemotherapy. No child received
ifosfamide. A clinically relevant 'nephrotoxicity score' was derived from GFR and
serum magnesium. Follow-up studies were performed in 16 children at 1 year and in
15 at 2 years after cisplatin. Considerable interpatient variability in
nephrotoxicity was observed. Treatment was modified in three patients because of
nephrotoxicity. GFR was low in 18 out of 31 patients. Proximal nephron toxicity
caused hypomagnesaemia in ten patients and hypocalcaemia in five patients.
Elevated urinary N-acetylglucosaminidase excretion was seen in 22 out of 30
children, indicating subclinical tubular toxicity. Nephrotoxicity was less severe
in children who received cisplatin courses at a dose rate of 40 mg m(-2) day(-1)
than in those who received higher dose rates (P < 0.005), but there was no
correlation with total dose received. Follow-up studies revealed partial recovery
of GFR (P < 0.05). Glomerular and proximal nephron toxicity are common in
children treated with cisplatin, and more severe at higher dose rates. Despite
partial recovery of GFR, the long-term outcome of nephrotoxicity remains unknown
and careful monitoring of chronic toxicity is necessary.
PMID- 9635849
TI - Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental
patients: a randomized crossover study.
AB - A double-blind randomized crossover trial was performed to compare the antiemetic
efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in
Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate
and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive
chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the
first cycle followed by the reverse order in the second cycle, or vice versa. The
number of vomiting episodes and the severity of nausea in the first 24 h (acute
vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied.
Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and
27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes)
occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely
controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with
ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each
agent (P = NS). However, complete response for delayed vomiting was observed in
only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P =
NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten
(25%) cycles respectively (P = NS). In conclusion, both granisetron and
ondansetron are effective in controlling acute nausea and vomiting in Chinese
patients, with equivalent antiemetic efficacy. Control of delayed nausea and
vomiting is less satisfactory.
PMID- 9635850
TI - Neuromuscular toxicities of paclitaxel 210 mg m(-2) by 3-hour infusion.
AB - We retrospectively analysed neuromuscular toxicity associated with paclitaxel 210
mg m(-2) given by 3-h infusion in 247 patients. The severity correlated
significantly with total cumulative dose, but could not be predicted by the
pretreatment clinical variables or by pharmacokinetic parameters. The toxicity
tended to occur in early treatment cycles.
PMID- 9635851
TI - Treatment-induced mucositis: an old problem with new remedies.
AB - Mucositis may be a painful, debilitating, dose-limiting side-effect of both
chemotherapy and radiotherapy for which there is no widely accepted prophylaxis
or effective treatment. The basis of management is pain relief, prevention of
dehydration and adequate nutrition. When tested vigorously, most antiseptic
mouthwashes and anti-ulcer agents are ineffective. Simple mechanical cleansing by
saline is the most effective traditional measure. A variety of new agents are
effective. Granulocyte macrophage colony-stimulating factor (GM-CSF) and
granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system
and can reduce mucositis, but the best schedule, dosage and method of
administration is not known or which is the best growth factor to prevent this
side-effect. A placebo-controlled randomized trial of antibiotic pastilles has
shown a significant reduction in mucositis and weight loss during radiotherapy
for head and neck cancer. Another method to reduce radiation effects in normal
tissue is to stimulate cells to divide before radiotherapy by silver nitrate or
interleukin 1. These methods may be particularly effective when given along with
hyperfractionated radiation treatment such as CHART.
PMID- 9635852
TI - Different patterns of stromal and cancer cell thymidine phosphorylase reactivity
in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival.
AB - Angiogenesis is recognized as an important step in tumour pathogenesis that is
related to invasion and metastatic spread and which consequently results in poor
clinical outcome. In this study, we have examined the role of tumour stroma
activated fibroblasts and macrophage infiltration in the development of the
angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A
total of 141 cases of early stage I-II NSCLC treated with surgery alone were
analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular
grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP)
reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP
overexpression related to high vascular grade and to advanced T stage (P = 0.0004
and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high
angiogenesis (P = 0.01), but was independent of cancer cell expression.
Fibroblast TP overexpression was related to abundant stroma (P = 0.003),
suggesting that TP may be a marker of active stroma. Moreover, intense macrophage
infiltration was associated with fibroblast TP reactivity, regardless of the
amount of stroma, suggesting that macrophages may be a major contributor to TP
expression in stroma. Survival analysis showed that cancer cell TP overexpression
was related to poor prognosis (P = 0.005). Although stroma TP is related to
angiogenesis, in the low vascular grade group it defined a group of patients with
better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an
indirect marker of tumour infiltration by functional macrophages, which have an
antitumour effect. We conclude that stromal macrophage and fibroblast TP
reactivity may have an important role in non-small-cell lung cancer behaviour.
Understanding the role of stromal fibroblasts and inflammatory cells and their
interaction with oncoprotein expression is essential for the elucidation of lung
cancer pathogenesis.
PMID- 9635853
TI - In oesophageal squamous cell carcinoma vascular endothelial growth factor is
associated with p53 mutation, advanced stage and poor prognosis.
AB - Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting
angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF.
We investigated the effect of VEGF on oesophageal carcinoma and the connection
between VEGF and p53. One hundred and nine resected oesophageal squamous cell
carcinomas were examined. VEGF expression was analysed by immunohistochemical
staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF
positive. A significant correlation was found between the VEGF expression and
both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001).
With regard to p53, we compared the expression of VEGF with the mutation of p53,
examined using polymerase chain reaction-single-strand conformation polymorphism
(PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who
we have reported previously. The VEGF expression was significantly correlated to
p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density
(MVD) was counted, and endothelial cells were stained immunohistochemically using
anti-CD34 monoclonal antibody against 29 cases with invasion limited to the
submucosal layer. The average MVD had a tendency to correlate to VEGF expression
(P = 0.1626). The prognoses of patients with VEGF-positive primary tumours were
significantly worse than for those with VEGF-negative primary tumours (P =
0.0077). We have assumed that VEGF contributes to aggressive characteristics in
oesophageal carcinomas and that VEGF expression might be affected by p53 status.
PMID- 9635854
TI - Encephalopathy, lactic acidosis, hyperammonaemia and 5-fluorouracil toxicity.
PMID- 9635855
TI - The multifaceted roles of nitric oxide in cancer.
AB - The roles of nitric oxide (NO) in numerous disease states have generated
considerable discussion over the past several years. NO has been labeled as the
causative agent in different pathophysiological mechanisms, yet appears to
protect against various chemical species such as those generated under oxidative
stress. Similarly, NO appears to exert a dichotomy of effects within the
multistage model of cancer. Chronic inflammation can lead to the production of
chemical intermediates, among them NO, which in turn can mediate damage to DNA.
Yet, NO also appears to be critical for the tumoricidal activity of the immune
system. Furthermore, NO can also have a multitude of effects on other aspects of
tumor biology, including angiogenesis and metastasis. This report will discuss
how the chemistry of NO may impact the initiation and progression stages of
cancer.
PMID- 9635856
TI - COX-2 expression is induced by UVB exposure in human skin: implications for the
development of skin cancer.
AB - Extensive documentation has validated the role of UV irradiation as a tumor
initiator and promoter, inducing both squamous and basal cell carcinomas. Human
epidermis is a tissue which undergoes active metabolism of arachidonic acid to
prostaglandins which is regulated by the action of prostaglandin H synthase (also
known as cyclooxygenase). One mechanism for the promotional activity of UV light
may involve its ability to induce prostaglandin formation. Work in our laboratory
has demonstrated that acute exposure of human keratinocytes to UVB irradiation
results in increased production of prostaglandin E2 (PGE2). When cultured human
keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro,
Western blot analysis showed a 6-fold increase in COX-2 protein which was evident
at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were
irradiated on sun-protected skin with up to four times their minimal erythema
dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression
was observed via immunofluorescence microscopy. RNAase protection assays
supported this observation, showing induction of COX-2 message which peaked at
approximately 12 h following irradiation in vitro. Furthermore, human squamous
cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein
via immunohistochemistry and Western analysis when compared to normal non-sun
exposed control skin. Together, these data demonstrate acute upregulation of COX
2 via UVB irradiation and suggest the need for further studies of COX-2
expression as a potential pharmacological target mediating human skin tumor
development.
PMID- 9635857
TI - DNA adducts, mutant frequencies and mutation spectra in lambda lacZ transgenic
mice treated with N-nitrosodimethylamine.
AB - Groups of lambda lacZ transgenic mice were treated i.p. with N
nitrosodimethylamine (NDMA) as single doses of 5 mg/kg or 10 mg/kg or as 10 daily
doses of 1 mg/kg and changes in DNA N7- or O6-methylguanine or the repair enzyme
O6-alkylguanine-DNA alkyltransferase (AGT) were followed for up to 14 days in
various tissues. Adduct induction in the liver exceeded by at least one order of
magnitude than observed in the next nearest target tissue (lung), and was
approximately linearly related to dose, except for O6-methylguanine after the
first dose of 1 mg/kg which was lower than expected. Substantial induction of
lambda lacZ mutagenesis was observed only in the liver, where the mutant
frequency was already maximal within 7 days after 5 mg/kg NDMA and remained
unchanged thereafter up to 49 days. Small but marginally significant increases in
mutant frequency were consistently observed in the spleen after all three modes
of treatment. A lack of proportionality between mutation induction and the
administered dose or the corresponding adduct levels was observed, probably
reflecting the importance of toxicity-related cell proliferation caused by NDMA
at higher doses. Twenty eight days after a dose of 10 mg/kg (causing a 3.6-fold
increase in mutant frequency), NDMA was found to increase the frequency of GC-
>AT mutations (with a concomitant shift of their preferential location from CpG
sites to GpG sites), which made up approximately 60% of the induced mutations.
Surprisingly, NDMA also caused a significant increase in deletions of a few (up
to 11) base-pairs (22%).
PMID- 9635858
TI - Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable
from p53 mutations in human skin cancer.
AB - Ultraviolet (UV) light has been associated with the development of human non
melanoma skin cancers (NMSC). Such cancers often exhibit mutations in the p53
tumour suppressor gene. In order to determine the UV-induced p53 mutation
spectrum, a yeast expression vector that harbours a human wild-type p53 cDNA was
UV-irradiated in vitro and transfected into a yeast strain that contained the
ADE2 gene regulated by a p53-responsive promoter. Forty-five mutant clones
contained 51 mutations. Seven mutations were tandem base pair substitutions, four
of which being CC-->TT, hallmark mutations of UV mutagenesis. Eighty percent
(41/51) of the mutations were single or non-tandem base pair substitutions, the
majority of which (27/41) were C-->T transitions. Ninety-five percent of such
mutations occurred at dipyrimidine sites. Through a rigorous statistical test,
the UV-induced p53 mutation spectrum appears to differ significantly (P < 0.008)
from the one induced by the antineoplastic drug chloroethyl-cyclohexyl
nitrosourea, and to be indistinguishable from the one observed in NMSC (P = 0.4).
These results demonstrate that the assay allows the determination of carcinogen
specific p53 mutation fingerprints and represents a new tool for molecular
epidemiology.
PMID- 9635859
TI - Restored gap junctional communication in non-tumorigenic HeLa-normal human
fibroblast hybrids.
AB - Gap junctional intercellular communication (GJIC) has been implicated in
homeostasis, development, differentiation, wound healing or regeneration and
adaptive responses of differentiated cells. The dysfunction of homologous or
heterologous GJIC has been associated with the tumorigenic phenotype. Restoration
of growth control and the suppression of the tumorigenic phenotype have been
previously associated with the up-regulation of GJIC by various anti-tumorigenic
chemicals or transfection of connexin genes into tumor cells. To test the
hypothesis that 'tumor suppressor' genes may be associated with the up-regulation
of GJIC, we tested clones of tumorigenic HeLa, several non-tumorigenic HeLa
normal human fibroblast somatic cell hybrids and a tumorigenic segregant of one
of the non-tumorigenic hybrids for GJIC. The parental HeLa cells (D98 AH.2) had
no detectable GJIC but expressed detectable connexin 43 transcripts, while the
non-tumorigenic HeLa-human fibroblast hybrids, which contained the chromosome 11
from the normal human fibroblast (CGL-1, CGL-2, ESH15 and EHS15c1), expressed
ample connexin 43 transcripts and showed proficient GJIC. The tumorigenic
segregant (CGL-3) from the non-tumorigenic HeLa-human fibroblast hybrid showed no
GJIC or connexin 43. These results show that the presence of GJIC is closely
linked to the suppression of the tumorigenic phenotype in the HeLa-human
fibroblast hybrid and further suggest that GJIC may be associated with the
mechanisms of tumor suppression. The mechanism by which the tumor suppressor
gene(s) on the normal chromosome in the HeLa-human fibroblasts induces the up
regulation of connexin 43 is not yet explained.
PMID- 9635860
TI - Sequence specific mutations induced by N-nitrosodimethylamine at two marker loci
in metabolically competent human lymphoblastoid cells.
AB - N-Nitrosodimethylamine (NDMA) is a potent mutagen and animal carcinogen to which
many people are exposed through the consumption of contaminated food and the use
of tobacco products. Although the mutational specificity of NDMA has been studied
in bacteria, little is known about the specific types of mutations induced by
NDMA in the human genome. Knowledge of the mutational spectrum of NDMA in human
genes may help to substantiate the role of NDMA in the etiology of human cancers.
In the current study, the mutational spectrum of NDMA was characterized at the tk
and hprt loci, in human lymphoblastoid cells capable of metabolically activating
NDMA. A number of patterns were observed among NDMA-induced mutations. At both
marker loci, G:C-->A:T transitions dominated the mutational spectrum of NDMA,
which were indicative of the mutagenicity of the O6meG lesion. In addition, the
majority of G:C-->A:T mutations occurred at guanines 3' to another guanine.
Almost all of these mutations originated on the non-transcribed strand, which
suggests that transcription-coupled repair influenced the distribution of G:C-
>A:T transitions at the tk and hprt loci. Furthermore, the observation of
hotspots for G:C-->A:T mutations, within both loci, suggests that differential
repair kinetics may exist, and consequently affect the distribution of mutations.
Finally, a comparison of the site specificity of G:C-->A:T mutations at the tk
and hprt loci, indicated that the gene used for mutational analysis influenced
the site specificity of NDMA-induced mutations, and possibly reflects the number
of 5'-GG-3' sites in the tk and hprt loci that when mutated would yield a mutant
phenotype.
PMID- 9635861
TI - Defining the minimal portion of the retinoblastoma protein that serves as an
efficient substrate for cdk4 kinase/cyclin D1 complex.
AB - We have determined the minimal portion of the retinoblastoma protein (Rb) that
can serve as an efficient substrate for in vitro phosphorylation by cdk4 kinase
D1 cyclin. Kinetic measurements indicate that in vitro, a 15-kDa fragment that
represents the C-terminus of Rb can serve equally well as a substrate when
compared with the larger 56-kDa fragment of Rb, which contains the A, B and C
domains. By comparison, peptide substrates appear to be 1000-fold less efficient.
Furthermore, mutational analysis indicates that not all of the five
phosphorylation sites within this minimal C domain are phosphorylated equally by
cdk4/D1. Ser795 is the preferred phosphorylation site, whereas the four remaining
sites Ser807, Ser811, Thr821 and Thr826 are phosphorylated to a much lesser
degree. Truncations of the C domain from the carboxy terminus indicate that
almost all of this domain is required for efficient phosphorylation. These data
suggest that the structural context of the phosphorylation site within the
substrate is critical for its phosphorylation by the cdk4/D1 kinase.
PMID- 9635862
TI - Functional characterization of the human CYP1A1 negative regulatory element:
modulation of Ah receptor mediated transcriptional activity.
AB - The mechanisms that underly the regulation of human CYP1A1 have merited
considerable attention because of their association both with toxic outcomes and
the etiology of several cancers. Previous work conducted in this laboratory has
identified a negative regulatory element (NRE) in the 5' region of this gene that
appeared to modulate CYP1A1 transcriptional activity. This NRE is present in two
functional copies, a high affinity 21-bp palindrome centered at position -784,
and an additional element found within a GC-rich region between position -728 and
-558. In this report, the regulatory function of the NREs in the context of the
CYP1A1 promoter was evaluated. This was accomplished by substituting mutated
elements for the corresponding wild-type element in a vector that contained human
CYP1A1 sequences positions -1140 to +59 directing the transcription of the
chloramphenicol acetyltransferase reporter gene. Expression vectors containing
specific mutations in each or both NREs were characterized. We show that
eliminating the binding of the CYP1A1 repressor protein to one or both repressor
motifs results in a significant 2- to 3-fold increase in the inducibility of
CYP1A1 promoter activity. Although mutation of both sites appeared to result in
an increase in inducibility over that observed with only one site mutated, the
effect was not additive. Such aberrant transcriptional activity correlates with
the highly inducible aryl hydrocarbon hydroxylase phenotype that is a reported
marker for individuals predisposed to lung cancer. Mutation of the NRE, or more
likely, the cognate repressor protein(s), may provide a genetic basis for this
phenotype.
PMID- 9635863
TI - The nuclear concentration of kin17, a mouse protein that binds to curved DNA,
increases during cell proliferation and after UV irradiation.
AB - UV-irradiation induces, in mammalian cells, the expression of a set of genes
known as the 'UV-response', which may be reminiscent of the bacterial response,
called SOS system. The multifunctional protein RecA controls the expression of
the SOS genes. We report the expression profile of a mouse gene conserved among
mammals, called Kin17, that codes a DNA-binding protein of undetermined
biochemical activity and which shares epitopes with the bacterial RecA protein.
We demonstrate that the level of Kin17 RNA was 5-fold higher in mid-S phase of
serum-stimulated BALB/c 3T3 fibroblasts than in quiescent cells. Cells in S-phase
displayed a high level of kin17 protein with a marked nuclear localisation. The
maximal level of Kin17 RNA was observed 18 h after serum stimulation, indicating
that Kin17 gene is a new member of the late growth-related genes. The
accumulation of kin17 protein during cell proliferation follows the increase in
Kin17 RNA and correlates with DNA synthesis, which suggests a possible role of
kin17 protein in a transaction related to DNA-replication. In quiescent
fibroblasts, a 3-fold increase in Kin17 RNA was seen 13 h after UV irradiation.
In parallel, kin17 protein accumulated in the nucleus, which suggests that it
might be required after the stress produced by UV irradiation.
PMID- 9635864
TI - Neocarzinostatin-induced mutations at the hprt locus in exponentially growing CHO
cells, compared with spontaneous mutations.
AB - Spontaneous mutations and neocarzinostatin-induced mutations were investigated in
the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in exponentially
growing Chinese hamster ovary cells. Neocarzinostatin (NCS) treatment caused an
4.5-fold increase in mutation frequency. Analysis by multiplex polymerase chain
reaction and sequencing of hprt cDNA revealed that spontaneous mutations in this
system were characterized by a relatively high rate of large deletions and double
base substitutions, and a low rate of splice mutations compared with data
reported in fibroblastic cell lines. NCS hardly affected this spectrum of
spontaneous mutations, which indicates the rare incidence of NCS-specific change
in the exponential growth phase. This is in contrast to aprt gene mutations
reported in plateau phase cells in which base substitutions occur preferentially
at sites affected by NCS. These results suggest that differences in the loci
assayed or in the processes involved in mammalian mutagenesis in the exponential
growth phase and the plateau phase may be the source of the different results.
PMID- 9635865
TI - The cellular stress response induced by aqueous extracts of cigarette smoke is
critically dependent on the intracellular glutathione concentration.
AB - Mainstream cigarette smoke (CS) trapped in phosphate-buffered saline solutions
(smoke-bubbled PBS) has been shown to induce a strong stress response in cultured
cells. This is reflected, for example, by the expression of stress genes such as
c-fos and haem oxygenase, a transient decrease in the translation efficiency and
the induction of cell cycle arrest. In these studies, peroxynitrite, the reaction
product of nitric oxide (NO) and superoxide (O2-.), was identified as an active
principle formed by CS in aqueous solutions. In the present study, we show that
the CS-induced stress response is critically dependent on the intracellular
glutathione (GSH) content which itself becomes diminished in cells exposed to
smoke-bubbled PBS. Investigations using c-fos expression as a measure for
cellular stress revealed a direct correlation between the smoke-bubbled PBS
concentration necessary for stress-dependent c-fos expression and the
intracellular GSH concentration observed in different cell lines.
Correspondingly, 3T3 fibroblasts artificially depleted of GSH by pretreatment
with buthionine-sulphoximine (BSO), an inhibitor of GSH synthesis, require
significantly lower amounts of smoke-bubbled PBS to obtain a detectable c-fos
expression, whereas, supplementation of the medium with N-acetyl-cysteine is an
efficient treatment for the inhibition of a CS-induced c-fos response. We also
show that the smoke-bubbled PBS-dependent loss of intracellular GSH is mainly
attributable to the aldehyde fraction of CS, although these aldehydes by
themselves cannot induce c-fos in these cells. The smoke-bubbled PBS-dependent c
fos response can, however, be mimicked when peroxynitrite and CS-related
aldehydes, at the concentrations calculated to appear in smoke-bubbled PBS, are
used in combination for cell exposure. Taken together, these results suggest that
in cells exposed to aqueous extracts of CS, smoke-related aldehydes decrease the
intracellular GSH content significantly, allowing peroxynitrite to interfere with
specific target molecules resulting in the stress-specific expression of c-fos.
PMID- 9635866
TI - Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and
intron primers.
AB - In mammals, one of the Mad homologues, Smad2, was reported to be a mediator of
TGF-beta signaling, and was found mutated in some cases of colon and lung
cancers. To extend the analysis of this gene, we previously investigated the
genomic organization of the human Smad2 gene and defined the structure of 12
exons and flanking introns. In this study, we designed 11 sets of intron-based
primers to examine the entire coding region of the Smad2 gene. By the PCR-SSCP
method using these primers, we screened genomic DNA sequences of colorectal
cancers for mutations of the Smad2 gene. Though there was no mutation within all
exons of the Smad2 gene, two of 60 sporadic colorectal cancers displayed
deletions in the polypyrimidine tract preceding exon 4. Deletions of this region
were also detected in colon cancer cell lines, and were clustered within cells
exhibiting microsatellite instability. Deletions in the polypyrimidine tract had
various effects on pre-mRNA splicing, but had no effect on the splicing of the
Smad2 gene in these cases. However, our data support the idea that the
polypyrimidine tract in the splicing acceptor site is a target of mutations in
mismatch repair-deficient tumors.
PMID- 9635867
TI - Responses of alveolar macrophages and epithelial type II cells to oxidative DNA
damage caused by paraquat.
AB - Because lung cells are inevitably exposed to chemicals, drugs and mineral
particles, they are appropriate target cells for investigating effects of
environmental toxins. We have studied alveolar macrophages and epithelial type II
pneumocytes freshly isolated from the rat lung, using the comet assay to detect
DNA damage (strand breaks and oxidized bases) in individual cells after treatment
with the pesticide paraquat. The background level of strand breaks is five times
higher in freshly isolated pneumocytes than in alveolar macrophages. This
difference remains even after 48 h of in vitro culture and therefore probably
does not reflect trauma suffered during isolation. In contrast, endogenous
formamidopyrimidine glycosylase- and endonuclease III-sensitive sites, which are
specific indicators of oxidative damage, are present in freshly isolated alveolar
macrophages but not in pneumocytes, reflecting the high metabolic activity of
macrophages and their defensive role. Both cell types are exquisitely sensitive
to strand breakage by paraquat. In addition, specific base oxidation is detected
after 24 h of treatment with paraquat, especially in alveolar macrophages.
Susceptibility to DNA damage, rather than lipid peroxidation, is likely to be the
cause of paraquat-induced death in these cells. The relatively high level of
endogenous damage in pneumocytes suggests that these cells are inefficient at DNA
repair, which would be consistent with their probable role as the principal
progenitors of lung cancer.
PMID- 9635869
TI - Differences in aromatic-DNA adduct levels between alveolar macrophages and
subpopulations of white blood cells from smokers.
AB - The 32P-post-labelling assay for DNA adduct quantification gives the opportunity
to examine endogenous exposure to DNA reactive compounds. Most human
biomonitoring studies applied white blood cells (WBC) or cells obtained by
broncho-alveolar lavages (BAL) as source of DNA, but still it is not clear what
cell type represents the most reliable indicator for exposure to cigarette smoke
associated genotoxins. At first, we examined DNA adduct levels by means of
nuclease P1 (NP1) enriched 32P-post-labelling in separated WBC subpopulations
after in vitro incubations for 18 h with 10 microM benzo[a]pyrene (B[a]P). DNA
adduct levels were highest in monocytes (10.7 +/- 2.9 adducts/10(8) nucleotides,
n = 8), followed by lymphocytes (5.9 +/- 1.7, n = 8), and granulocytes (0.5 +/-
0.2, n = 8). Secondly, aromatic-DNA adduct levels were determined in BAL cells
and WBC-subsets from (non-)smoking volunteers. In smoking individuals, adduct
levels were in the ranking order: BAL cells (3.7 +/- 1.0, n = 5) > monocytes (2.0
+/- 0.5, n = 8) > or = lymphocytes (1.6 +/- 0.4, n = 8) > granulocytes (0.8 +/-
0.2, n = 8) by NP1-enrichment and monocytes (9.0 +/- 3.2, n = 5) > or =
lymphocytes (8.0 +/- 2.1, n = 6) > granulocytes (2.1 +/- 0.3, n = 7) by butanol
enriched 32P-post-labelling. Aromatic-DNA adduct levels were significantly higher
in WBC-subsets of smokers as compared with non-smokers, except for DNA adducts in
granulocytes using butanol enrichment. Thirdly, dose-response relationships were
investigated in mononuclear white blood cells (MNC, i.e. monocytes plus
lymphocytes) and BAL-cells of a larger group of smoking individuals (n = 78).
Adduct levels in MNC were related to daily exposure to cigarette-tar (r = 0.31, P
< 0.01). Adduct levels in BAL cells seemed to be correlated with pack-years, but
after correction for age this relationship was lost. Butanol extraction resulted
in 5-6-fold higher DNA adduct levels in MNC, whereas butanol extraction of BAL
DNA of the same individuals yielded only 2-fold higher adduct levels. The two
enrichment procedures of 32P-post-labelling were correlated in BAL cells (r =
0.86, P < 0.001, n = 12). We conclude that particularly MNC are good surrogates
for the detection of smoking-related DNA adducts.
PMID- 9635868
TI - Lung cancer risk and CYP1A1 genotype in African Americans.
AB - The role of CYP1A1 genotype in lung cancer risk was assessed in African Americans
through a case control study. The complete CYP1A1 genotype, including the
frequency of all three polymorphisms (Msp1 [CYP1A1*2], exon 7 [CYP1A1*3] and
African American specific [CYP1A1*4]) was determined by PCR on 307 controls and
105 cases of lung cancer among African Americans. We have confirmed our earlier
observation of a significant increased risk (odds ratio = 2.8, 95% CI = 1.3-6.5)
for lung adenocarcinoma among people with the *4 polymorphism, although we did
not observe any association of this polymorphism with overall lung cancer risk.
As previously reported, we found that lung adenocarcinoma patients with the *4
RFLP smoked significantly less than patients without this polymorphism,
suggesting an important role in cancer risk of low exposure levels to cigarette
smoke in subjects carrying susceptibility polymorphisms. There was no association
with the other two polymorphisms and lung cancer in this population. When we
examined lung cancer risk as a function of composite genotype, taking into
account all three polymorphisms simultaneously in each subject, our preliminary
data suggested an association of one rare genotype (homozygous Msp1, heterozygous
exon 7 or *2/*2*3) with overall lung cancer risk (OR = 8.4, 95% CI = 1.6-43.2).
PMID- 9635870
TI - Modulation of small G protein isoprenylation by anticancer monoterpenes in in
situ mammary gland epithelial cells.
AB - Monoterpenes have been shown to both prevent and treat mammary cancer in animal
models and are currently in clinical testing in advanced cancer patients. In this
study, we investigated a biochemical modulation associated with the antitumor
activity of monoterpenes, the inhibition of protein isoprenylation in monoterpene
chemoprevention target tissue, i.e. the in situ mammary gland epithelial cells.
We first developed a new methodology that for the first time permitted the study
of protein isoprenylation and other products in the mevalonate pathway in in situ
mammary cells. Using this approach, we found that chronically feeding rats with
an anticancer dose of perillyl alcohol resulted in a 22% inhibition of coenzyme Q
synthesis and a 19% inhibition of small G protein isoprenylation in mammary gland
epithelial cells in situ. The greatest inhibition of small G protein
isoprenylation observed was the 28% inhibition of isoprenylation of RhoA by type
I geranylgeranyl protein transferase (GGPTase). Given that some substrates of
type I GGPTase, such as RhoA and Rac1, have transforming properties, the
possibility that the inhibition of type I GGPTase will change the cellular
location and functionality of these proteins and thus contribute to the
chemoprevention activity of monoterpenes, is discussed.
PMID- 9635871
TI - Maspin gene expression in tumor suppression induced by overexpressing manganese
containing superoxide dismutase cDNA in human breast cancer cells.
AB - We have reported the tumor suppressive effects of manganese-containing superoxide
dismutase (MnSOD) in human breast cancer cells. In order to understand the
molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor
gene(s), especially the ones inhibiting tumor invasion and motility, are involved
in MnSOD-induced tumor suppression. Maspin is one of the serpin family of
protease inhibitors that has been shown to function as a tumor-suppressor in
human breast epithelium. In the present study, we demonstrated that maspin
expression was up-regulated in human breast cancer MCF-7 cells that overexpress a
normal MnSOD gene. The induced maspin transcripts were detected by RT-PCR and
Northern blot and identified by sequencing. Maspin gene expression was induced in
parallel with the level of exogenous MnSOD protein, which was induced by
transfection with varied amounts of cDNA. In order to analyze cell invasion
ability, which may be related to the induced maspin gene expression, MnSOD stable
transfectants were tested using a matrigel invasion chamber. The invasion ability
was reduced to 24% and 36% in the cloned (MCF + SOD) and pooled MnSOD
transfectants (MCF + SODp) respectively, compared with the wild-type MCF-7 cell
line. In conclusion, these results suggest that overexpression of a normal MnSOD
cDNA in human breast cancer cells up-regulates the gene expression of the
protease inhibitor, maspin, which may play a role in the inhibitory function of
MnSOD on tumor invasion.
PMID- 9635872
TI - Smoking-associated bulky DNA adducts in bronchial tissue related to CYP1A1 MspI
and GSTM1 genotypes in lung patients.
AB - Relationships between smoking status and levels of bulky DNA adducts were
investigated in bronchial tissue of lung patients in relation to their GSTM1 and
CYP1A1 MspI genotypes. A total of 150 Hungarian patients undergoing pulmonary
surgery were included in the study, 124 with lung malignancies and 26 with non
malignant lung conditions. There were significant relationships between smoking
status and bulky DNA adduct levels, as determined by 32P-post-labelling analysis,
in macroscopically normal bronchial tissues. There was a highly significant
difference in the adduct levels of a combined group consisting of current smokers
and short-term ex-smokers (< or = 1 year abstinence) compared with life-time non
smokers and long-term ex-smokers (> 1 year abstinence) (P = 0.0001). The apparent
half-life was estimated to be 1.7 years for bulky DNA adducts in the bronchial
tissue from ex-smokers. There were no statistically significant correlations
between (i) daily cigarette dose and DNA adduct levels in current smokers, (ii)
DNA adduct level and histological type of lung cancer, or (iii) GSTM1 and CYP1A1
MspI genotypes and DNA adduct levels after adjustment for either smoking status
or malignancy. By multiple logistic regression analysis, smoking and GSTM1 null
genotype were found to be risk factors for squamous cell carcinoma. However,
bulky DNA adduct levels in bronchial tissue did not appear to be a statistically
significant risk factor for the major histological types of lung cancer.
PMID- 9635873
TI - X-ray-induced lymphomagenesis in E mu-pim-1 transgenic mice: an investigation of
the co-operating molecular events.
AB - Transgenic mice overexpressing the pim-1 oncogene in their lymphoid compartment
display a low incidence of spontaneous T-cell lymphomas, but are highly
susceptible to point mutation-inducing genotoxic carcinogens. We show here that
total body X-irradiation, which causes mainly chromosomal deletions,
rearrangements and amplifications, significantly enhances lymphoma development in
E mu-pim-1 transgenic mice. The X-ray-induced E mu-pim-1 and non-transgenic
lymphomas have a comparable high cell turnover as shown by a relatively high S
phase fraction and a high apoptotic activity. Consistent with previous
observations, in 75% of all lymphomas c-myc mRNA levels are 5- to 20-fold higher
than in control, non-lymphomatous spleen/thymus. The expression of other
oncogenes, which have previously found to be activated in combination with pim-1
in lymphomagenesis, such as gfi-1/pal-1, frat-1 and tiam-1, and also of the mdm-2
and mdm-x oncogenes, appeared not to be affected. Deletions and/or rearrangements
of the p16INK4A and p15INK4B tumor suppressor genes were seldom observed (in
three out of 92 X-ray-induced lymphomas). Strikingly, in addition to the high
mRNA levels of the pim-1 transgene, the levels of the endogenous pim-1
transcripts were elevated significantly in 16% of the X-ray-induced E mu-pim-1
lymphomas compared with control spleen, even surpassing the level of the pim-1
transgene mRNA by 3- to 5-fold. In combination with previous results, which
showed that the lymphoma incidence increased concordantly with higher levels of
pim-1, this supports the notion that pim-1 can contribute to lymphomagenesis in a
dose-dependent manner.
PMID- 9635874
TI - Clonal analysis of urothelial carcinomas in C3H/HeN<-->BALB/c chimeric mice
treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.
AB - The histological background for multifocal and metachronous development of
urothelial carcinomas remains equivocal, although accumulated genetic evidence
suggests monoclonal origin of multiple urothelial carcinomas. Clonal development
of various preneoplastic and neoplastic urothelial lesions of C3H<-->BALB/c
chimeric mice induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was
immunohistochemically investigated using a C3H strain-specific antibody. All
tumor masses induced in the mice treated with 0.05% BBN for 20 weeks were
composed of neoplastic cells of a single parental type, which is indicative of
monoclonal lesions. Three of 10 animals harbored two or more separate carcinomas
of different clonal type, which is indicative of multicentric development
applicable in this model. Using DNAs derived from urothelial carcinomas and tumor
adjacent urothelium of chimeric mice, polymerase chain reaction-single strand
conformation polymorphism (PCR-SSCP) analysis and direct sequencing were
performed for p53 gene exons 5-7. p53 mutations were identified in four of 11
(36%) dysplasias and non-invasive carcinomas (carcinoma in situ and pTa tumor)
and 13 of 22 (59%) invasive carcinomas. Only in a single case were identical p53
mutations found in separate urinary bladder carcinomas. In contrast to the random
distribution of urothelial proliferating units in chimeric mice without chemical
supplement, invasive carcinomas in BBN-treated mice were accompanied by widely
distributed preneoplastic and neoplastic lesions of the same clonality, which
occasionally had frequent foci of microinvasion. This is indicative of lateral
clonal expansion of the clones, which precedes the bulk of invasive carcinomas.
Thus, two aspects of 'field change' of the urothelium became evident in this
model: either independent transformation events or lateral clonal expansion
might, respectively, result in multicentric and monoclonal carcinoma development
in the urinary tract.
PMID- 9635875
TI - The metabolic activation of tamoxifen and alpha-hydroxytamoxifen to DNA-binding
species in rat hepatocytes proceeds via sulphation.
AB - The biotransformation pathway of tamoxifen and alpha-hydroxytamoxifen to DNA
binding species was investigated in rat hepatocytes in vitro. Rat hepatocytes
were isolated by in situ collagenase perfusion and then maintained in sulphate
free Dulbecco's modified Eagle's medium. Magnesium sulphate was added to the
medium to give concentrations of 0-10 microM, prior to treatment for 18 h with
solvent vehicle (DMSO), tamoxifen (10 microM), alpha-hydroxytamoxifen (1 microM)
or benzo[a]pyrene (BaP) (10 and 50 microM). DNA was isolated and analysed by 32P
post-labelling. For tamoxifen and alpha-hydroxytamoxifen, the level of DNA adduct
formation was directly proportional to the concentration of sulphate in the
medium. Between 0 and 10 microM MgSO4, the DNA adduct level increased 10-fold
with both compounds. Rat hepatocytes were also maintained in normal Dulbecco's
modified Eagle's medium and pretreated with dehydroisoandrosterone-3-sulphate
(DHEAS, a sulphotransferase inhibitor) at concentrations ranging from 0-1 mM,
prior to treatment with solvent vehicle (DMSO), tamoxifen (10 microM), alpha
hydroxytamoxifen (1 microM) or BaP (50 microM). For tamoxifen and alpha
hydroxytamoxifen the level of DNA adducts was reduced to approximately one-fifth
by the addition of DHEAS (0.1 mM). BaP-DNA adduct formation, which proceeds by a
pathway that does not require sulphation, was not significantly affected by
sulphate concentration or by addition of DHEAS, which demonstrates that the
general metabolic capacity and viability of the hepatocytes were not compromised.
It is concluded that the activation of tamoxifen in rat liver cells to DNA
binding products proceeds predominantly through hydroxylation followed by
sulphate ester formation at the alpha-position of the ethyl side chain.
PMID- 9635876
TI - 16Alpha-hydroxylation of estrone by human cytochrome P4503A4/5.
AB - The cytochrome P450 (P450) enzymes that catalyse metabolism of the estrogen,
estrone (E1), to the putative carcinogen 16alpha-hydroxy E1 (16alpha-OHE1) in
humans were determined. The potential of the most abundant circulating form of
estrogen, estrone 3-sulfate (E1S), to be the substrate was also investigated.
Human liver microsomal sulfatases convert E1S to E1, an essential prerequisite
for formation of 16alpha-OHE1 from added E1S in this system. E1 metabolism to
16alpha-OHE1 in a panel of 15 human liver microsomal preparations correlated with
total P450 concentrations (r2 = 0.63) and with activities associated with P450
forms CYP3A4 and 3A5 (r2 = 0.72). E1 16alpha-hydroxylase activity in human liver
microsomes was inhibited by 75% by monoclonal anti human CYP3A4/5 antibodies at 4
mg antibody/nmol total P450, and by troleandomycin, a specific CYP3A4/5
inhibitor. Rates of E1 metabolism to 16alpha-OHE1 were 1.6-fold higher when E1
was generated in situ from E1S than when E1 was added. Microsomal preparations of
cDNA expressed CYP3A4 or 3A5, with NADPH-P450-reductase co-expressed, both
metabolized E1 to 16alpha-OHE1, and added cytochrome b5 increased the rates 5.1-
and 7.5-fold, respectively. In these systems rates of E1 metabolism to 16alpha
OHE1 were 2.8-fold higher when E1 was generated in situ from E1S than when E1 was
added. Kinetic values for E1 metabolism to 16alpha-OHE1 by human liver microsomes
and for the expressed CYP3A4 system were Km 154 and 172 microM, respectively, and
Vmax 238 pmol/min/nmol total P450 and 1050 pmol/min/nmol CYP3A4, respectively.
Thus, formation of the putative carcinogen 16alpha-OHE1 is catalysed by CYP3A4
and 3A5 and stimulated by cytochrome b5. E1S is not a substrate but formation of
E1 from E1S in situ stimulates formation of 16alpha-OHE1, possibly because E1S is
more water soluble and in situ generation of E1 provides for facilitated exposure
of E1 to the P450 substrate binding sites. Blocking of the pathway of E1 to
16alpha-OHE1 could provide a therapeutic approach for diminishing the risk of
estrogen dependent breast cancer.
PMID- 9635877
TI - Interindividual variation in the metabolic activation of heterocyclic amines and
their N-hydroxy derivatives in primary cultures of human mammary epithelial
cells.
AB - The heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino
3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6
phenylimidazo[4,5-b]pyridine (PhIP) are pyrolysis products formed when meat is
cooked and are rodent mammary carcinogens. They are thought to be metabolically
activated by N-hydroxylation, catalysed by cytochrome P450 (CYP), followed by O
acetylation catalysed by N-acetyltransferases. Primary cultures of human mammary
epithelial cells (HMECs) prepared from up to 26 individuals for each compound,
were treated with IQ, MeIQ, or PhIP (500 microM) or with N-hydroxy-2-amino-1
methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) or N-hydroxy-2-amino-3
methylimidazo[4,5-f]quinoline (N-OH-IQ) (20 microM) and the levels of adduct
formation in their DNA analysed by 32P-post-labelling. In order to investigate
whether pharmacogenetic polymorphisms influence DNA adduct formation, the NAT2
genotype of each individual was determined by a polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP) method that distinguishes
between the wild-type and four variant alleles. Presence of two variant alleles
designates a slow NAT2 acetylator, whereas individuals with one or two wild-type
alleles are designated fast NAT2 acetylators. Interindividual variations in total
DNA adduct levels ranged for IQ from 0.64-63.1 DNA adducts per 10(8) nucleotides
(mean 7.80), for MeIQ from 1.99-17.8 (mean 6.63), for PhIP from 0.13-4.0 (mean
0.96), for N-OH-PhIP from 6.32-497 (mean 176) and for N-OH-IQ from 0.92-30.6
(mean 9.24). The higher adduct levels observed in cells treated with the N-OH
metabolites suggests that N-hydroxylation is the rate-limiting step in HMECs and
this may be due to low CYP levels. In contrast, the Phase II reaction catalysed
by N-acetyltransferases is probably the major step in the metabolic activation of
heterocyclic amines that occurs in the breast. Higher mean levels of heterocyclic
amine-DNA adduct formation were detected in the cells of NAT2 fast acetylators
compared with slow acetylators, with mean adduct levels per 10(8) nucleotides
following IQ treatment, of 12.74 and 3.57 respectively, following PhIP treatment,
of 1.20 and 0.74, respectively, following MeIQ treatment, of 7.90 and 5.08,
respectively and following N-OH-PhIP-treatment, of 243.1 and 130.0, respectively.
However, due to the large variations in adduct levels, these differences in mean
values were not statistically significant with the limited number of individuals
studied. This appears to be the first pilot study to demonstrate interindividual
variations in the metabolic activation of heterocyclic amines and their metabolic
intermediates in primary cultures of HMECs in vitro.
PMID- 9635878
TI - Effect of 3-aminotriazole on anchorage independence and mutagenicity in cadmium-
and lead-treated diploid human fibroblasts.
AB - Cadmium and lead have been shown to induce cellular transformations and gene
mutations in cultured rodent cells, as well as tumours in live animals. However,
the mechanisms by which these metals cause cellular transformations and mutations
in human cells have not been explored. In this study, we investigated the
abilities of cadmium and lead to induce anchorage-independent transformations and
hprt gene mutations in diploid human fibroblasts. Human fibroblasts were exposed
to either cadmium acetate (0-60 microM) or lead acetate (0-2 mM) for 24 h. After
removal of the metals, the cells were kept in exponential growth for 7 and 9 days
before mutation and anchorage-independence assays were taken, respectively. Both
cadmium and lead significantly induced anchorage-independent colonies in dose
dependent manners; the frequencies of anchorage-independent colonies induced by
these metals were similar to those induced by N-methyl-N'-nitro-N
nitrosoguanidine at approximately equal cytotoxic dose ranges (30-10% survival).
3-Aminotriazole at non-cytotoxic dosages decreased catalase activity by >80%, and
markedly enhanced cadmium-induced cytotoxicity and anchorage-independent
colonies. Cadmium uptake by human fibroblasts was not affected by 3-aminotriazole
co-administered with 10 microM of cadmium; whereas cadmium uptake and
accumulation were enhanced 1.5-fold by 3-aminotriazole co-administered with 1-2.5
microM of cadmium. Lead-induced anchorage-independence or cytotoxicity was not
affected by 3-aminotriazole co-treatment; however, 3-aminotriazole did
significantly enhance lead uptake and accumulation in human fibroblasts. Neither
cadmium- nor lead-induced 6-thioguanine-resistant mutation frequency in human
fibroblasts. Co-administering these metals with 3-aminotriazole did not enhance
mutations in human fibroblasts. These results suggest that cadmium and lead may
both act as tumour promoters in diploid human fibroblasts, and that reactive
oxygen species is more important in cadmium- than lead-induced cytotoxicity and
anchorage-independence.
PMID- 9635879
TI - Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3
cells.
AB - Arsenical compounds, known to be human carcinogens, were shown to disturb cell
cycle progression and induce cytogenetic alterations in a variety of cell
systems. We report here that a 24 h treatment of arsenite induced mitotic
accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35%
of the total cell population was arrested at the mitotic stage after treatment
with 5 microM sodium arsenite in HeLa S3 cells and after 10 microM in KB cells.
Under a microscope, we observed abnormal mitotic figures in arsenite-arrested
mitotic cells, including deranged chromosome congression, elongated polar
distance of mitotic spindle, and enhanced microtubule immunofluorescence. The
spindle microtubules of arsenite-arrested mitotic cells were more resistant to
nocodazole-induced dissolution than those of control mitotic cells. According to
turbidity assay, arsenite at concentrations below 100 microM significantly
enhanced polymerization of tubulins. Since spindle dynamics play a crucial role
in mitotic progression, our results suggest that arsenite-induced mitotic arrest
may be due to arsenite's effects on attenuation of spindle dynamics.
PMID- 9635880
TI - Over-expression of glutathione S-transferase Yp isozyme and concomitant down
regulation of Ya isozyme in renal cell carcinoma of rats induced by ferric
nitrilotriacetate.
AB - An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal
tubular damage, a consequence of iron-catalysed Fenton-like reactions, that
finally leads to a high incidence of renal cell carcinoma (RCC) in rodents.
Glutathione S-transferase (GST) is a family of enzymes that play an important
role in detoxification of hydrophobic and electrophilic molecules, and has been
associated with putative preneoplastic foci of rat hepatocarcinogenesis and
chemotherapy-resistance of human cancers. Our previous study revealed an
induction of pi-class glutathione S-transferase (Yp) mRNA in the kidney 3 h after
administration of Fe-NTA. In the present study, expression of GST isozymes were
further investigated in the Fe-NTA-induced RCCs of rats which are characterized
by (1) high incidence of metastasis and invasion, (2) high incidence of tumour
associated mortality, and (3) possible involvement of reactive oxygen species in
carcinogenesis. In the Fe-NTA-induced RCCs, the levels of alpha-class GST (Ya)
mRNA and proteins were markedly decreased with no apparent change in the copy
number of the gene. In contrast, GST-Yp mRNA and proteins were significantly
increased in the RCCs while the total GST enzymatic activity was decreased.
Immunohistochemical analysis revealed intense staining of GST-Yp not only in the
primary RCCs and its metastatic sites, but also in their non-tumorous part of
proximal tubules. The contrastive expression of GST isozymes in this renal
carcinogenesis model suggests an alteration of its transcription mechanisms and
warrants further investigation of this particular detoxifying enzyme from the
viewpoint of reactive oxygen species-induced carcinogenesis.
PMID- 9635881
TI - The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression
of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands.
AB - Dietary n-6 polyunsaturated fatty acids (PUFAs) promote rat mammary cancer while
n-3 PUFAs are inhibitory. The purpose of this study was to determine whether the
fats exert their effects by altering the expression of genes that affect cancer
development. Therefore, we have examined the effect of PUFAs on the expression of
the cyclooxygenase (COX) 1 and 2 genes that are involved in prostaglandin
biosynthesis. We also investigated the effect of dietary PUFAs on the expression
of the p21ras protein and Ha-ras mRNA. Rats were fed either low- (7%; LF) or high
(21%; HF) fat diets that were rich in either n-6 PUFAs (safflower oil, S) or n-3
PUFAs (menhaden oil, M) for 3 weeks. COX-1 mRNA levels were approximately the
same in groups fed diets containing either level of menhaden oil, but were
increased by approximately 30% in the LFS and HFS groups (P < 0.05). Transcripts
of the inducible COX-2 gene were not detectable in the menhaden oil groups, but
this gene was expressed in animals fed either level of safflower oil and in the
HFS group was associated with increased levels of COX enzymatic activity and
production of PGE2. Animals fed safflower oil had elevated levels of p21ras
protein compared to animals fed menhaden oil. Ha-ras mRNA was increased by
approximately 35% in animals fed HFS compared to the group fed HFM (P < 0.05).
These results demonstrate that dietary n-6 PUFAs upregulate COX-2 and, to some
extent, COX-1 expression. There was a concomitant increase in COX enzyme activity
and PG synthesis in the mammary glands of rats fed high levels of n-6 PUFAs.
Together with associated changes in p21ras expression, these results may explain,
at least in part, the promoting effects of dietary n-6 PUFAs on mammary
carcinogenesis.
PMID- 9635882
TI - N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine formation by
peroxidative metabolism.
AB - N'-(3'-Monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is thought to
play an important role in initiation of benzidine-induced bladder cancer in
humans. This report assesses the possible formation of this adduct by peroxidatic
activation of N-acetylbenzidine (ABZ). Adduct formation was measured by 32P-post
labeling. Ram seminal vesicle microsomes were used as a source of prostaglandin H
synthase (PHS). The peroxidatic activity of PHS was compared with that for
horseradish peroxidase. Both peroxidases converted ABZ to dGp-ABZ whether DNA or
2'-deoxyguanosine 3'-monophosphate (dGp) was present. Following 32P-post
labeling, the enzymatic and synthetic adduct were extracted from PEI-cellulose
plates and were shown to have the same HPLC elution profiles for the bisphosphate
adduct (32P-dpGp-ABZ). Treatment of the enzymatic and synthetic bisphosphate
adduct with nuclease P1 yielded a product that eluted at the same time from the
HPLC (32P-dpG-ABZ). Additional experiments demonstrated that the PHS-derived 5'
monophosphate (dpG-ABZ) and 3'-monophosphate (dGp-ABZ) adducts were also
identical to their corresponding synthetic standard. With comparable amounts of
total ABZ metabolism, PHS produced approximately 40-fold more dGp-ABZ than
horseradish peroxidase (1943 +/- 339 versus 49 +/- 7.8 fmol/mg dGp). Adduct
formation was dependent upon the presence of peroxidase and the specific
substrate, i.e. arachidonic acid or H2O2. Adduct formation by PHS was inhibited
by indomethacin (0.1 mM), ascorbic acid (1 mM) and glutathione (10 mM), but not
by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) (100 mM), a radical scavenger.
Horseradish peroxidase adduct formation was also inhibited by ascorbic acid and
glutathione. In addition, DMPO elicited greater than a 96% inhibition. Results
demonstrate peroxidatic metabolism of ABZ to form dGp-ABZ. The mechanism of dGp
ABZ formation by PHS and horseradish peroxidase may be different.
PMID- 9635883
TI - Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
(PhIP) in female rats and their pups at dietary doses.
AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary carcinogen in
female rats and is present in a wide variety of cooked meats. We address here the
excretion of PhIP and its metabolites into the breast-milk of lactating rats and
the ability of chlorophyllin, a food product derivative with chemopreventive
properties, to affect these levels at low PhIP doses. Lactating female F344 rats
with suckling pups were orally administered 50, 500 and 1000 ng [14C]PhIP/kg body
weight. The excretion of the [14C]PhIP into milk and its distribution among the
mammary tissue, liver and blood of the dam, as well as among stomach contents and
liver of their suckling pups was measured using accelerator mass spectrometry
(AMS). PhIP, PhIP-4'-sulfate, 4'-hydroxy-PhIP, and N2-hydroxy-PhIP-N3-glucuronide
were found in the milk at all doses. The chlorophyllin (500 microg/kg) co
administration with PhIP (500 ng/kg) caused increased levels of [14C]PhIP in the
milk (32%) and stomach contents (35%) of the pups relative to the animals not
receiving chlorophyllin at these low PhIP doses. In contrast, lower [14C]PhIP
levels in the chlorophyllin treated animals were observed in the blood (47%) and
mammary tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared
to the animals receiving only PhIP. Chlorophyllin co-administration resulted in
an increased amount of N2-hydroxy-PhIP-N3-glucuronide (42%), increased PhIP (79%)
and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not
receiving chlorophyllin. These results suggest that PhIP and PhIP metabolites are
present in the breast-milk of lactating rats at human dietary PhIP exposures and
that PhIP is absorbed by the newborn. Furthermore, these results suggest that
other dietary components can affect the dosimetry of PhIP in breast-feeding
offspring.
PMID- 9635884
TI - The peroxisome proliferators are hepatocyte mitogens in chemically-defined media:
glucocorticoid-induced PPAR alpha is linked to peroxisome proliferator
mitogenesis.
AB - Peroxisome proliferator-induced mitogenesis is believed to play a role in
hepatocarcinogenesis, but it has not been possible to demonstrate high level
induction of DNA synthesis by peroxisome proliferators in cultured hepatocytes.
We now show that four structurally dissimilar peroxisome proliferators
(methylclofenapate, Wy-14 643, tetradecyl-3-thia acetic acid and clofibrate)
cause high level induction of DNA synthesis in primary cultures of rat
hepatocytes, routinely 7-9 fold above control, with up to 29% of cells undergoing
S-phase. Peroxisome proliferators induce DNA synthesis rapidly, with maximal
response 24 h after dosing [compared with 48 h for epidermal growth factor
(EGF)]; indeed, peroxisome proliferators were mitogenic in a chemically defined
medium, i.e. with no added exogenous growth factors. EGF-treated hepatocytes that
had undergone DNA synthesis comprised 23% binucleated cells, whereas hepatocytes
induced into S-phase by peroxisome proliferators contained only 3% binucleated
cells, demonstrating a distinct response of hepatocytes to peroxisome
proliferators and EGF. The presence of a glucocorticoid was essential for
peroxisome proliferator-induced DNA synthesis, but not for EGF-induced DNA
synthesis, demonstrating that the requirement for glucocorticoids is selective
for peroxisome proliferators. Hydrocortisone was shown to induce the expression
of peroxisome proliferator activated receptor-alpha (PPAR alpha), and we propose
that it is the glucocorticoid-induced expression of PPAR alpha that is essential
for peroxisome proliferator mitogenesis. This in vitro system provides a powerful
tool for investigating the mechanism and role of peroxisome proliferator-induced
mitogenesis in liver growth and carcinogenesis.
PMID- 9635885
TI - Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine
and dinitrosocaffeidine in bd-ix rats.
AB - Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso
compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product
of caffeine present in a typically made and widely consumed tea from Kashmir
(India), a high incidence area of esophageal and stomach cancer. The chemical
synthesis, in vitro metabolic studies and mutagenicity of the compounds has been
previously reported. DNC, a nitrosamide is highly mutagenic both with and without
metabolic activation whereas MNC, like several other aromatic asymmetric
nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report
the results of the first carcinogenicity experiments on chronic oral
administration of these compounds in BD-IX rats. The acute LD50 of MNC and DNC
were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and
gastrointestinal haemorrhages were the first symptoms of intoxication observed
after 2 days for both the compounds. All three dose groups of MNC treated rats
showed localization of tumours in nasal cavity (93.9-100% of all malignant
tumours). The tumours were histologically diagnosed as neuroepitheliomas of the
olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell
carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity
were observed in the untreated controls. DNC, in contrast, induced squamous cell
carcinoma of forestomach in 100% animals at low and high doses, of which nearly
half the tumours metastasized predominantly into the peritoneum. No forestomach
tumours were seen in the untreated controls. The data presented here clearly show
the potential for induction of malignant tumours and distinct organ-specificity
by MNC and DNC in rats, and support the postulate that a chronic exposure to
these compounds may provide a carcinogenic risk for high incidence of
gastrointestinal cancers in Kashmir.
PMID- 9635886
TI - 2,3-epoxy-4-hydroxynonanal, a potential lipid peroxidation product for etheno
adduct formation, is not a substrate of human epoxide hydrolase.
AB - Our previous studies have shown that 2,3-epoxy-4-hydroxynonanal, a reactive epoxy
aldehyde capable of forming etheno adducts with DNA bases, is mutagenic and
tumorigenic (Carcinogenesis, 14, 2073). The epoxy aldehyde can be generated from
trans-4-hydroxy-2-nonenal, a lipid peroxidation product of omega-6
polyunsaturated fatty acids, by autoxidation or by incubation with fatty acid
hydroperoxides or hydrogen peroxides (Chem. Res. Toxicol., 9, 306). These are
plausible in vivo pathways for the formation of 2,3-epoxy-4-hydroxynonanal. The
possibility that 2,3-epoxy-4-hydroxynonanal is a tumorigen of endogenous origin
is suggested by recent observations that etheno bases are detected as background
DNA lesions in untreated rodents and humans. A metabolic pathway critical for
detoxification of 2,3-epoxy-4-hydroxynonanal involves the ring-opening by epoxide
hydrolase, which abolishes its ability to form cyclic etheno DNA adducts. In this
study, we examined whether 2,3-epoxy-4-hydroxynonanal is a substrate of cDNA
expressed human epoxide hydrolase. Human epoxide hydrolase was expressed in TK-
143 cells (thymidine kinase-deficient human embryoblast) infected with
recombinant vaccinia virus encoding human epoxide hydrolase cDNA. Controls
consisted of the cells infected with vaccinia virus in the absence of human
epoxide hydrolase cDNA. No hydrolysis occurred when [2,3-(3)H]2,3-epoxy-4
hydroxynonanal was incubated at 37 degrees C for 30 min at pH 7.4 with cells
expressing human epoxide hydrolase, as indicated by the presence of a pair of
radioactive peaks in reversed-phase HPLC chromatography, which comigrated with
the UV standards of the two diastereomers of the epoxy aldehyde. The identity of
these compounds as the intact epoxy aldehyde was further supported by
derivatization to the 2,4-dinitrophenylhydrazones followed by reversed phase HPLC
analysis. Similar results were observed with the control cells or with the heat
deactivated human epoxide hydrolase. The epoxide hydrolase activity in the
expressed cells was demonstrated by their ability to convert benzo[a]pyrene-4,5
dihydroepoxide to benzo[a]pyrene-trans-4,5-dihydrodiol under the same conditions.
These results clearly indicate that 2,3-epoxy-4-hydroxynonanal is not a substrate
of human epoxide hydrolase, and, thus strengthen its possible endogenous role in
the formation of promutagenic exocyclic etheno adducts in vivo.
PMID- 9635887
TI - Identification, chromosomal mapping and tissue-specific expression of hREV3
encoding a putative human DNA polymerase zeta.
AB - The Saccharomyces cerevisiae REV3 gene encodes the catalytic subunit of a non
essential DNA polymerase zeta, which is required for mutagenesis. The rev3
mutants significantly reduce both spontaneous and DNA damage-induced mutation
rates. We have identified human cDNA clones from two different libraries whose
deduced amino acid sequences bear remarkable homology to the yeast Rev3, and
named this gene hREV3. The hREV3 gene was mapped to chromosome 1p32-33 by
fluorescence in situ hybridization. The hREV3 encodes an mRNA of >10 kb, and its
expression varies in different tissues and appears to be elevated in some but not
all of the tumor cell lines we have examined. In light of recent reports of a
putative mouse REV3, these results indicate that mammalian cells may also contain
a mutagenic pathway which aids in cell survival at the cost of increased
mutation.
PMID- 9635888
TI - Molecular characterization of ST1C1-related human sulfotransferase.
AB - Carcinogenic arylamines such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) are
metabolically activated by mammalian sulfotransferases to form N-hydroxyarylamine
O-sulfates. We previously showed that rat ST1C1 efficiently mediate these
activations. These reactions occur in liver cytosols of humans as well as rats.
However, the enzyme responsible for N-OH-AAF activation has not been identified
in humans. In the present study, a human cDNA (ST1C2) encoding a sulfotransferase
showing a high similarity with ST1C1, has been isolated from a human fetal liver
cDNA library and expressed using a bacterial expression system. A clear
difference was observed in the pH optima for p-nitrophenol sulfation between
ST1C2 and ST1C1 expressed in Escherichia coli. In addition, ST1C2 did not mediate
3'-phosphoadenosine-5'-phosphosulfate-dependent DNA binding of N-OH-AAF. These
results suggest that human ST1C2 has a clear different substrate specificity, in
spite of the structural similarity, with rat ST1C1.
PMID- 9635889
TI - Callosal terminals in the rat prefrontal cortex: synaptic targets and association
with GABA-immunoreactive structures.
AB - The callosal projections of the cerebral cortex play an important role in the
functional integration of the two hemispheres, and the anatomy of these
connections has been extensively studied in primary sensory and motor regions. In
the present investigation, we examined the synaptic targets of callosal terminals
in a limbic association area, the prefrontal cortex (PFC) in the rat. In
addition, we examined the relationship of callosal afferents to GABA local
circuit neurons within the PFC. Callosal terminals were labeled by either
anterograde transport of Phaseolus vulgaris leucoagglutinin from superficial or
deep layers or by anterograde degeneration following electrolytic lesion of the
contralateral PFC. Callosal terminals in either the superficial or deep layers
labeled by either method formed primarily asymmetric axo-spinous synapses
(approximately 95%), while the remainder formed axo-dendritic synapses. Some of
the dendrites postsynaptic to callosal terminals exhibited a morphology
characteristic of local circuit neurons. This observation was confirmed in tissue
immunolabeled for GABA, in which degenerating callosal terminals sometimes formed
asymmetric synapses on GABA-labeled dendrites. In addition, GABA-labeled
terminals and callosal afferents were sometimes observed to converge onto common
postsynaptic dendritic shafts or spines within the PFC. These results indicate
that callosal terminals in limbic association cortex, consistent with sensory and
motor cortices, primarily target the spines of pyramidal neurons. In addition,
the results suggest that callosal afferents to the PFC interact with GABA local
circuit neurons at multiple levels. Specifically, a proportion of callosal
terminals appear to provide excitatory drive to GABA cells, while GABA terminals
may modulate the excitation from callosal inputs to the distal dendrites and
spines of PFC pyramidal neurons.
PMID- 9635890
TI - Effects of overexpression of the cytoplasmic copper-zinc superoxide dismutase on
the survival of neurons in vitro.
AB - The cytoplasmic copper-zinc superoxide dismutase (Cu, Zn SOD; SOD-1) is an
abundant and well-conserved intracellular antioxidant enzyme which has been
implicated in a number of oxidative stress mediated phenomena, especially Down
Syndrome, in which SOD-1 activity is increased due to triplication of chromosome
21 containing the gene and, in hereditary amyotrophic lateral sclerosis, in which
the gene is mutated. Overexpression of SOD-1 could theoretically, therefore, lead
to increased vulnerability to oxidative stress in two distinct manners:
increasing steady-state hydrogen peroxide levels or increasing toxic side
reactions. We used two mouse neuronal culture systems--one in which the murine
chromosome containing SOD-1 is triplicated and one in which human SOD-1 is a
transgene--to test the effect of overexpression of this enzyme on antioxidant
status in general and specifically on glutamate mediated oxidative stress. We
found that SOD-1 overexpression increases antioxidant status at the same time it
decreases vulnerability to glutamate.
PMID- 9635891
TI - Selective blockade of a slowly inactivating potassium current in striatal neurons
by (+/-) 6-chloro-APB hydrobromide (SKF82958).
AB - The ion channels of rat striatal neurons are known to be modulated by stimulation
of D1 dopamine receptors. The susceptibility of depolarization-activated K+
currents to be modulated by the D1 agonist, 6-chloro-7,8-dihydroxy-3-allyl-1
phenyl-2,3,4,5-tetra-hydro-1H-3-benzaze pine (APB) was investigated using whole
cell voltage-clamp recording techniques from acutely isolated neurons. APB (0.01
100 microM) produced a concentration-dependent reduction in the total K+ current.
At intermediate concentrations (ca. 10 microM), APB selectively depressed the
slowly inactivating A-current (I(As)). A similar effect was produced by
application of the D1 agonist, 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1-H-2
benzazepine (SKF38393, 10 microM). APB reduced I(As) rapidly, having onset and
recovery time constants of 1.2 sec and 1.6 sec, respectively. Unexpectedly, the
effect of APB could not be mimicked by application of Sp-adenosine 3',5'-cyclic
monophosphothioate triethylamine (Sp-cAMPS, 100-200 microM), a membrane-permeable
analog of cyclic AMP (cAMP), or by pretreatment with forskolin (25 microM), an
activator of adenylyl cyclase. The reduction in I(As) also was not blocked by
pretreatment with the D1 receptor antagonist, R(+)-SCH23390 hydrochloride
(SCH23390, 10-20 microM). In addition, intracellular dialysis with guanosine-5'-O
(2-thiodiphosphate (GDP-beta-S, 200 microM) did not preclude the APB-induced
inhibition of I(As), nor did dialysis with guanosine-5'-O-(3-thiotriphosphate
(GTP-gamma-S, 400 microM) prevent reversal of the effect. The effect of APB was
produced by a reduction in the maximal conductance of I(As) without changing the
voltage-dependence of the current. Collectively, these results argue that APB
does not inhibit I(As) through D1 receptors coupled to stimulation of adenylyl
cyclase, but rather by allosterically regulating or blocking the channels giving
rise to this current.
PMID- 9635892
TI - 6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced
parkinsonism in monkeys.
AB - This report describes a method to assess, in vivo, the turnover of dopamine (DA)
and describes its application to the evaluation of DA function in normal monkeys
and monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
lesions of the DA nigro-striatal pathway. Using positron emission tomography with
the tracer of presynaptic DA function, 6-[18F]fluoro-L-DOPA (FDOPA), and an
extension of the graphical method of analysis, we measured the striatal FDOPA
uptake rate constant, Ki, and the rate of reversibility of FDOPA trapping k(loss)
in normal and MPTP-treated monkeys, either neurologically normal or displaying a
parkinsonian symptomatology. An index of effective DA turnover was defined as the
ratio of k(loss)/Ki. Compared to normal controls, Ki was decreased and k(loss)
was increased in the MPTP-lesioned monkeys. The index of DA turnover was
significantly increased in the monkeys displaying a parkinsonian symptomatology
as compared to the controls and the neurologically normal MPTP-treated monkeys.
The DA turnover index was also significantly increased in the neurologically
normal MPTP-lesioned animals compared to normals. This suggests that an increase
in DA turnover develops early in the disease process and may be one of the
compensatory mechanisms partly responsible for the delay in the development of
the clinical manifestations in Parkinson's disease.
PMID- 9635893
TI - Ng-nitro-L-arginine, an NOS inhibitor, reduces tolerance to morphine in the rat
locus coeruleus.
AB - Ng-nitro-L-arginine (L-NArg), a potent nitric oxide synthase inhibitor, has been
implicated as a potential mechanism for attenuating the development of tolerance
to opioid drugs and for suppressing opioid withdrawal. Neurons in the locus
coeruleus (LC) express opioid receptors and these neurons exhibit both tolerance
to chronic administration of opioids and antagonist-precipitated withdrawal
hyperactivity. This study tested the hypothesis that L-NArg would attenuate the
development of opioid tolerance in LC neurons. Challenge doses of morphine were
administered while recording single-cell extracellular activity in brain slices
from rats who had been concurrently treated for 5 days with morphine (75 mg
morphine sulfate base pellets) and L-NArg (10 mg/kg, i.p., bid). The average ED50
for morphine of cells from rats who received L-NArg injections and morphine
pellets was similar to that in cells from rats who had been implanted with sham
pellets (14.5-18 nM). In contrast, the average ED50 of cells from morphine
pelleted animals who received saline injections was substantially higher (34.5
nM). These results demonstrate that L-NArg attenuates the development of
tolerance to morphine in LC neurons.
PMID- 9635894
TI - Ultrastructural localization of mu-1 opioid receptor in the dorsal raphe nucleus
of the rat.
AB - A simple pre-embedding avidin-biotin-peroxidase complex technique was used to
study the ultrastructural localization of mu-1 opioid receptor in the rat dorsal
raphe nucleus. Using low concentrations of the first antiserum for incubation
with a short reaction time to 3,3'-diaminobenzidine, the immunostaining was faint
at the light microscopic level. However, at the electron microscopic level strong
immunoreaction was observed. Mu-1 opioid receptors were found to be localized on
the postsynaptic membrane of dendrites, extra-synaptic plasma membrane, and the
surface of the small, clear vesicles in axon terminals. Of the total 407
immunopositive profiles observed, 76.4% (311/407) were dendrites and 18.9%
(77/407) were axon terminals. The immunostained myelinated axons and perikarya
were relatively rare, with frequencies of 1.0% (4/407) and 3.7% (15/407),
respectively. About 50.8% of the immunopositive dendrites (158/311) were
immunostained having their MOR-LI results beneath the postsynaptic membrane,
although about 19.6% of them (31/158) also exhibited MOR-LI on other components,
including the extrasynaptic plasma membrane. Other immunopositive dendrites
showed staining in some other contents, including extrasynaptic plasma membrane
(82/311, 26.4%) or not on the plasma membranes (71/311, 22.8%). Less than half of
the immunopositive axon terminals (35/77, 45.5%) were found to make synapses with
nonimmunoreactive dendrites (31/77, 40.3%) or immunopositive dendrites (4/77,
5.2%); none were found to make synapses with immunoreactive perikarya. The
present study shows that mu-1 opioid receptor in the dorsal raphe nucleus plays a
role at both synapse or not.
PMID- 9635895
TI - Differential inhibition of catecholamine secretion by amitriptyline through
blockage of nicotinic receptors, sodium channels, and calcium channels in bovine
adrenal chromaffin cells.
AB - We investigated the effects of amitriptyline, a tricyclic antidepressant, on
[3H]norepinephrine ([3H]NE) secretion and ion flux in bovine adrenal chromaffin
cells. Amitriptyline inhibited [3H]NE secretion induced by 1,1-dimethyl-4
phenylpiperazinium iodide (DMPP) and 70 mM K+. The half maximal inhibitory
concentration (IC50) was 2 microM and 9 microM, respectively. Amitriptyline also
inhibited the elevation of cytosolic calcium ([Ca2+]i) induced by DMPP and 70 mM
K+ with IC50 values of 1.1 microM and 35 microM, respectively. The rises in
cytosolic sodium ([Na+]i) and [Ca2+]i induced by the Na+ channel activator
veratridine were also inhibited by amitriptyline with IC50 values of 7 microM and
30 microM, respectively. These results suggest that amitriptyline at micromolar
concentrations inhibits both voltage-sensitive calcium (VSCCs) and sodium
channels (VSSCs). Furthermore, submicromolar concentrations of amitriptyline
significantly inhibited DMPP-induced [3H]NE secretion and [Ca2+]i rise, but not
veratridine- or 70 mM K+-induced responses, suggesting that nicotinic
acetylcholine receptors (nAChR) as well as VSCCs and VSSCs can be targeted by
amitriptyline. DMPP-induced [Na+]i rise was much more sensitive to amitriptyline
than the veratridine-induced rise, suggesting that the influx of Na+ and Ca2+,
through the nAChR itself is blocked by amitriptyline. Receptor binding
competition analysis showed that binding of [3H]nicotine to chromaffin cells was
significantly affected by amitriptyline at submicromolar concentrations. The data
suggest that amitriptyline inhibits catecholamine secretion by blocking nAChR,
VSSC, and VSCC.
PMID- 9635896
TI - Inhibition of NMDA-receptor mediated response in the rat medial prefrontal
cortical pyramidal cells by the 5-HT3 receptor agonist SR 57227A and 5-HT:
intracellular studies.
AB - The techniques of intracellular recording and single-electrode voltage-clamp were
used to study the effect of serotonin (5-HT) and the selective 5-HT3 receptor
agonist SR 57227A on N-methyl-D-aspartic acid (NMDA)-evoked responses in
pyramidal cells of the rat medial prefrontal cortex (mPFC) in in vitro brain
slice preparations. Bath application of 5-HT or SR 57227A produced a
concentration-dependent inhibition of NMDA-induced membrane depolarization,
action potentials, and inward current. The depressant action of 5-HT and SR
57227A had a slow onset and showed no signs of receptor desensitization. This
action was markedly attenuated or completely blocked by the selective 5-HT3
receptor antagonists granisetron and BRL 46470A, but not other receptor
antagonists. In addition to inhibiting NMDA-evoked responses, SR 57227A also
depressed significantly pharmacologically isolated, NMDA receptor-mediated,
monosynaptic excitatory postsynaptic currents (EPSCs) elicited by electrical
stimulation of the forceps minor; this inhibitory action was blocked by BRL
46470A but not other 5-HT receptor antagonists. Perfusion of Ca2+-free or low
Ca2+ plus Cd2+ artificial cerebrospinal fluid prevented electrical stimulation
induced EPSCs, but did not affect the inhibitory action of 5-HT and SR 57227A. In
conclusion, we demonstrate for the first time that 5-HT and SR 57227A interact
with 5-HT3-like receptors to produce a direct inhibitory action on NMDA receptor
mediated response in pyramidal cells of the mPFC.
PMID- 9635897
TI - Differential effects of chronic haloperidol administration on midbrain dopamine
neurons in Sprague-Dawley, Fischer 344, and Lewis rats: an in vivo
electrophysiological study.
PMID- 9635898
TI - Acute and chronic administration of clozapine produces greater proconvulsant
actions than haloperidol on focal hippocampal seizures in freely moving rats.
AB - In this study, we assessed the effects of the acute (a single injection) and
repeated (once daily injections for 21 days) administration of the atypical
antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) and the typical
antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/kg, i.p.) on hippocampal
partial seizures generated by low-frequency electrical stimulation in male Wistar
rats. The seizure threshold and severity were determined by measuring the pulse
number threshold (PNT) and the primary afterdischarge duration (ADD),
respectively. A single injection of either 5 or 15 mg/kg of clozapine
significantly decreased the PNT and significantly increased the primary ADD,
indicating a proconvulsant action. The repeated administration of clozapine (1.5,
5, or 15 mg/kg, i.p.) produced dose-dependent, proconvulsant effects by
significantly decreasing the PNT and by significantly increasing the primary ADD.
In contrast to clozapine, the acute administration of haloperidol did not
significantly alter the PNT or the primary ADD. The repeated administration of
haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased
the primary ADD, but did not alter the PNT. Overall, clozapine produces a greater
proconvulsant action than haloperidol in an animal model of hippocampal seizures.
PMID- 9635899
TI - Immature chemodifferentiation of Purkinje cell synapses revealed by 5'
nucleotidase ecto-enzyme activity in the cerebellum of the reeler mouse.
AB - During postnatal development of the rodent cerebellum, a transient enzyme
activity of ecto-5'-nucleotidase has been shown in the asymmetrical synapses of
Purkinje cells. The alterations of the afferent circuitry and microenvironment of
the ectopic Purkinje cells present in the cerebellum of the reeler mutant mouse
could enlighten parameters that influence the synaptic 5'-nucleotidase activity
of these cells. Ecto-enzyme cytochemistry reveals intense 5'-nucleotidase
activity in 43% of synapses of the Purkinje cells throughout the cortex and the
core of the reeler cerebellar vermis, although the molecular layer displays large
areas with less than 1% of labelled synapses. However, enzymatic labelling is
found in considerably more Purkinje cells synapses (73%) throughout the granular
layer and the subcortical mass. Climbing fiber synapses of monoinnervated
Purkinje cells are labelled by 5'-nucleotidase activity in the molecular layer,
as well as asymmetrical synapses made on the subjacent ectopic Purkinje cells by
the multiple climbing fibers and by the heterologous afferences. The non
innervated dendritic spines of these cells are also labelled, suggesting that 5'
nucleotidase activity at postsynaptic sites of reeler Purkinje cells does not
depend on the presynaptic innervation. Rather, 5'-nucleotidase enzyme activity is
enhanced at theses sites when the Purkinje cells have not achieved
chemodifferentiation but have conserved immature wiring, i.e., low parallel fiber
and multiple climbing fiber inputs.
PMID- 9635900
TI - Acanthamoeba keratitis.
AB - Acanthamoeba species are an important cause of microbial keratitis that may cause
severe ocular inflammation and visual loss. The first cases were recognized in
1973, but the disease remained very rare until the 1980s, when an increase in
incidence mainly associated with contact lens wear was reported. There is an
increased risk when contact lens rinsing and soaking solutions are prepared with
nonsterile water and salt tablets. The clinical picture is often characterized by
severe pain with an early superficial keratitis that is often treated as herpes
simplex infection. Subsequently a characteristic radial perineural infiltration
may be seen, and ring infiltration is common. Limbitis and scleritis are
frequent. Laboratory diagnosis is primarily by culture of epithelial samples
inoculated onto agar plates spread with bacteria. Direct microscopy of samples
using stains for the cyst wall or immunostaining may also be employed. A variety
of topically applied therapeutic agents are thought to be effective, including
propamidine isethionate, clotrimazole, polyhexamethylene biguanide, and
chlorhexidine. Various combinations of these and other agents have been employed,
often resulting in medical cure, especially if treatment is commenced early in
the course of the disease. Penetrating keratoplasty is preferably avoided in
inflamed eyes, but may be necessary in severe cases to preserve the globe or,
when the infection has resolved, to restore corneal clarity for optical reasons.
PMID- 9635901
TI - Assessment of human ocular hemodynamics.
AB - Vascular abnormality and altered hemodynamics play important roles in many
ophthalmic pathologies. Much of our knowledge of ocular hemodynamics was gained
from invasive animal research, although a number of noninvasive methods suitable
for in vivo use in humans have been developed. Data from these methods now
produce a significant literature of their own. Understanding the origins of the
data and appreciating their limitations can be difficult. Modern hemodynamic
assessment techniques each examine a unique facet of the ocular circulation. No
single facet provides a complete description of the hemodynamic state of the eye.
These methods have contributed a great deal to our understanding of normal
hemodynamics. More importantly, they continue to add to our understanding of
altered hemodynamics found in disease. Some have found their way into limited
clinical practice. The predominant ocular hemodynamic assessment techniques are
reviewed with the aims of introducing the fundamental principles behind each,
highlighting their inherent advantages and limitations, highlighting their
contributions to understanding ocular physiology, and considering their potential
to provide signs for diagnosis.
PMID- 9635902
TI - The association between cigarette smoking and ocular diseases.
AB - Tobacco smoke is composed of as many as 4,000 active compounds, most of them
toxic on either acute or long-term exposure. Many of them are also poisonous to
ocular tissues, affecting the eye mainly through ischemic or oxidative
mechanisms. The list of ophthalmologic disorders associated with cigarette
smoking continues to grow. Most chronic ocular diseases, with the possible
exception of diabetic retinopathy and primary open-angle glaucoma, appear to be
associated with smoking. Both cataract development and age-related macular
degeneration, the leading causes of severe visual impairment and blindness, are
directly accelerated by smoking. Other common ocular disorders, such as retinal
ischemia, anterior ischemic optic neuropathy, and Graves ophthalmopathy, are also
significantly linked to this harmful habit. Tobacco smoking is the direct cause
of tobacco-alcohol amblyopia, a once common but now rare disease characterized by
severe visual loss, which is probably a result of toxic optic nerve damage.
Cigarette smoking is highly irritating to the conjunctival mucosa, also affecting
the eyes of nonsmokers by passive exposure (secondhand smoking). The dangerous
effects of smoking are transmitted through the placenta, and offspring of smoking
mothers are prone to develop strabismus. Efforts should be directed toward
augmenting the campaign against tobacco smoking by adding the increased risk of
blindness to the better-known arguments against smoking. We should urge our
patients to quit smoking, and we must make them keenly aware of the afflictions
that can develop when smoke gets in our eyes.
PMID- 9635903
TI - The Francis I. Proctor Foundation: the first fifty years.
AB - September 15, 1997 marked the golden anniversary of the Francis I. Proctor
Foundation, which was established in affiliation with the University of
California in San Francisco. Over 50 years, 182 fellows from 27 countries have
been trained in programs focusing on the study of infectious and inflammatory eye
disease, and the prevention of blindness worldwide. Many of the people and events
that have contributed to the success of the Proctor Foundation are presented in
this brief essay.
PMID- 9635904
TI - Drug-induced uveitis.
AB - Uveitis has been reported in association with a variety of topical, intraocular,
periocular, and systemic medications. To establish causality of adverse events by
drugs, in 1981, Naranjo and associates proposed seven criteria, which are related
to the frequency and documentation of the event; circumstances of occurrence,
recovery, and recurrence; and coexistence of other factors or medications. Rarely
does a drug meet all seven criteria. The authors review reports of drug
associated uveitis, applying the seven criteria and examining possible
mechanisms. Only systemically administered biphosphonates and, perhaps, topical
metipranolol meet all seven criteria. Systemic sulfonamides, rifabutin, and
topical glucocorticoids fulfill at least five criteria.
PMID- 9635905
TI - The child with divergence paresis.
AB - Divergence paralysis is a rare clinical entity that causes a comitant esotropia
at distance. While this is usually benign and self-limited, there are reports of
divergence paralysis associated with brain tumors, central nervous system
syphilis, trauma, and multiple sclerosis. We studied a 14-year-old girl who
presented with diplopia and was found to have divergence paralysis. Magnetic
resonance imaging disclosed a large pontomedullary glioma.
PMID- 9635906
TI - Comparison of six rapid agglutination tests for the identification of
Staphylococcus aureus, including methicillin-resistant strains.
AB - Six rapid agglutination tests for the identification of Staphylococcus aureus
were evaluated by testing 416 strains of staphylococci. The sensitivities and
specificities of the tests were as follows: Staphyloslide, 97.7% and 99.3%
respectively; Prolex Staph Latex, 96.9% and 93.6%; Staphaurex, 95.4% and 94.2%;
Staphaurex Plus, 100% and 93.4%; Slidex Staph Plus, 98.9% and 99.3%; and
Staphytect Plus, 99.6% and 88.2%. The three tests utilizing latex particles
coated with staphylococcal capsular antibodies were better able to identify
methicillin-resistant S. aureus, but only Staphyloslide and Slidex Staph Plus had
adequate specificity.
PMID- 9635907
TI - Optimal recovery of cytomegalovirus from urine as a function of specimen
preparation.
AB - Cytomegalovirus (CMV) is a significant pathogen among immunocompromised patients.
We compared supernatant and sediment fractions of centrifuged urine for the
optimal recovery of CMV by shell vial culture and polymerase chain reaction
(PCR). Of 336 urine specimens, 31 (9.23%) were positive by shell vial culture; of
these 29 (93.5%) were identified using the sediment fraction and 17 (54.8%) using
the supernatant fraction (p = 0.001, chi2). Of the 29 positive sediment fraction
specimens, 24 (82.8%) were identified as CMV positive at 24 h and 5 (17.2%) were
identified as positive at 48 h. Two (0.064%) of the total 31 positive specimens
were lost to microbial contamination in the sediment inoculated cultures. Of the
17 supernatant fraction specimens, 9 (53.9%) were identified as CMV positive at
24 h and 8 (47.1%) were identified as positive at 48 h. Fourteen (45.2%) of the
total 31 positive specimens were lost to either toxicity or microbial
contamination in the sediment-inoculated cultures. Thirty-four CMV culture
positive specimens were tested by PCR; 5 of these specimens (14.7%) were PCR
negative for both sediment and supernatant fractions; 26 (76.5%) were found to be
positive using the sediment fraction and negative using the supernatant; 3 (8.8%)
were PCR positive for both the sediment and the supernatant. None of the 34 was
identified as positive using the supernatant fraction only (p = 0.001, chi2).
These findings demonstrate that the method of specimen preparation can
significantly affect the outcome of diagnostic testing for CMV from urine
specimens.
PMID- 9635908
TI - In vitro activities of six fluoroquinolones against Canadian isolates of
vancomycin-sensitive and vancomycin-resistant Enterococcus species.
AB - The in vitro activities of six fluoroquinolones were determined against 1482
Enterococcus species isolates collected as part of a 1996 Canadian surveillance
study. Clinafloxacin MIC90s were 4 or 8 microg/mL, trovafloxacin and BAY 12-8039
MIC90s were 8 or 16 microg/mL, sparfloxacin MIC90s were 32 microg/mL, and
ciprofloxacin and ofloxacin MIC90s were >32 microg/mL for the vancomycin
sensitive Enterococcus faecalis, vancomycin-sensitive Enterococcus faecium, and
vancomycin-resistant E. faecium isolates collected.
PMID- 9635909
TI - Comparative antimicrobial activity and kill-curve investigations of novel
ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus
influenzae and Moraxella catarrhalis strains.
AB - The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those
of five macrolides, quinupristin/dalfopristin, ciprofloxacin, and ampicillin. The
rate of killing for the ketolides was also assessed against Haemophilus
influenzae and Moraxella catarrhalis. One hundred H. influenzae and 148 M.
catarrhalis isolates were tested using broth microdilution and appropriate growth
media. The killing rates of HMR 3004 and 3647 were analyzed using the time-kill
method against five strains from each of the two species. Against H. influenzae,
the activity of the ketolides (MIC90, 2 or 4 microg/mL) resembled that of
azithromycin and quinupristin/dalfopristin and was more active than any tested
macrolide. Against M. catarrhalis, HMR 3004 and 3647 were equally potent as
azithromycin and clarithromycin (MIC50, 0.06 microg/mL and MIC90, 0.12 microg/mL)
and more potent than all other macrolides or quinupristin/dalfopristin. Time-kill
kinetic studies revealed that like the macrolide compounds, the ketolides are
bacteristatic at or near the MIC for both H. influenzae and M. catarrhalis. This
activity can be increased to a bactericidal level if the concentration is
increased four- or eightfold the MIC for H. influenzae. In conclusion, HMR 3004
and 3647 have bacteristatic activity against tested respiratory pathogens and may
prove to have an important role against macrolide-resistant isolates.
PMID- 9635910
TI - Piperacillin/tazobactam versus imipenem: a double-blind, randomized formulary
feasibility study at a major teaching hospital.
AB - With the introduction of piperacillin/tazobactam to the North American market,
hospitals have been faced with the task of making a decision regarding its
formulary role. In view of its broad spectrum of activity,
piperacillin/tazobactam could be considered as a formulary alternative to
imipenem. To evaluate the formulary feasibility of substituting
piperacillin/tazobactam for imipenem, a comparative assessment of these agents in
the empiric treatment of serious bacterial infections was undertaken at this
tertiary care hospital. This trial was conducted as a randomized, double-blind,
single-center study. Consenting adult patients (>16 years of age) who were
prescribed imipenem were randomized to receive either 4 g of i.v.
piperacillin/tazobactam or imipenem 500 mg of i.v. Q6H with or without concurrent
antibiotics. Doses were adjusted according to renal function. There were no
restrictions regarding the use of nonstudy antibiotics before and during the
study period. Patients with beta-lactam allergies or meningitis or who had
received greater than 72 h of previous imipenem therapy were excluded. Patients
were evaluated at the end of treatment, at discharge, and at 30 days
postdischarge. Endpoints included both clinical and microbiologic efficacy as
well as drug toxicity. Over the 433-day study period, 360 imipenem treatment
courses were initiated. Of these, 150 treatment courses (75
piperacillin/tazobactam courses and 75 imipenem courses) met study criteria and
were subsequently randomized. The distribution of prescriber services for
enrolled patients was similar to that for all patients receiving imipenem during
the study period (p = 0.15). Also, there were no statistically significant
differences in demographic parameters between enrolled and excluded patients. For
those patients enrolled in the study, demographic characteristics, treatment
course indication(s), and accompanying antibiotics were similar across treatment
arms. The mean duration of study drug therapy was 7.7 days (SD, 6.2) for imipenem
and 7.5 days (SD, 6.7)for piperacillin/tazobactam (p = 0.84). In the majority of
cases, treatment discontinuation occurred as a result of a favorable treatment
course outcome, stepdown to a narrower spectrum parenteral agent, or stepdown to
an oral agent and did not differ between study drugs (p = 0.73). Clinical and
microbiologic treatment course outcomes were also similar across treatment arms.
Clinical outcome was deemed successful or improved for 68% of imipenem and 70% of
the piperacillin/tazobactam treatment courses (p = 0.54). Fifty-three percent of
treatment courses were microbiologically confirmed. Of the 58 courses that were
assessed for microbiological outcome, 93% demonstrated successful eradication of
the causative pathogens. There was no difference between study drugs (96%
imipenem; 90% piperacillin/tazobactam; p = 0.61). The proportion of treatment
courses with at least one adverse event was similar between the study drugs (p =
1.0). Nausea and/or vomiting were/was observed more commonly in the imipenem arm
(p = 0.03). Discontinuation of therapy due to drug toxicity occurred in 16% of
imipenem and 5% of piperacillin/tazobactam treatment courses (p = 0.06). There
was no statistically significant difference between the mean treatment course
cost for imipenem ($762; range, $55-$3192) versus piperacillin/tazobactam ($696;
range, $79-$2967; p = 0.59). In summary, piperacillin/tazobactam seems to
represent a suitable alternative to imipenem for several clinical indications
including intraabdominal infections, pneumonia, febrile neutropenia, and
skin/soft tissue infections in which the causative pathogens are susceptible.
However, in view of the prevalence of multiresistant Gram-negative aerobic
pathogens at this institution, we do not believe that imipenem can be removed
from the drug formulary. In addition, at the currently studied dosing regimen,
there seems to be no evidence of a direct cost advantage associated with
PMID- 9635911
TI - AIDS-related Mycobacterium kansasii infection with initial resistance to
clarithromycin.
AB - Clarithromycin is a promising drug for the treatment of Mycobacterium kansasii
infection. We report a patient with AIDS and severe M. kansasii infection who had
previously received a short course of clarithromycin for sinusitis. He had
clinical failure of treatment using clarithromycin plus ethambutol, and the
initial isolate was found to be highly resistant to clarithromycin. Nucleotide
sequencing of the 23S rRNA gene of this isolate demonstrated a single base
mutation at position 2058, the same as that found in clarithromycin-resistant
Mycobacterium avium.
PMID- 9635912
TI - Combinations of orally administered beta-lactams to maximize spectrum and
activity against drug-resistant respiratory tract pathogens: I. Synergy studies
of amoxicillin and cefixime with Streptococcus pneumoniae.
AB - Streptococcus pneumoniae strains have emerged that are resistant to penicillin
(MICs >0.06 microg/mL) and many other beta-lactams. However, some older compounds
such as amoxicillin have potency against these pneumococci with altered
penicillin-binding proteins, but are labile to beta-lactamases produced by other
prevalent respiratory tract pathogens. The interactions of amoxicillin with an
enzyme-stable cephalosporin (cefixime) with a long elimination half-life were
examined by the checkerboard dilution method versus 39 S. pneumoniae strains (13
resistant, 15 intermediate, and 11 susceptible to penicillin). Among 24 strains
with evaluable drug interaction tests, 17 (71%) demonstrated partial or complete
synergy. This favorable interaction produces a cefixime susceptibility category
change from resistant or intermediate to susceptible for 16 of 28 strains (57%),
when combined with < or = 1 microg/mL amoxicillin. Thus, the use of two currently
available oral beta-lactams (amoxicillin twice a day + cefixime once a day; three
total doses) appears to be a potential alternative treatment with greater
spectrum for community-acquired respiratory tract infections pending clinical
trial results.
PMID- 9635913
TI - Bacterial resistance: a worldwide problem.
AB - The therapeutic crisis produced by emerging antimicrobial resistances has
compromised the chemotherapy of hospitalized patients with serious infections.
For the most prevalent resistance problems, meropenem, a new carbapenem, appears
to provide a potency and spectrum for: 1) extended-spectrum beta-lactamase
producing Enterobacteriaceae; 2) Bush-Jacoby-Merdeiros group 1 enzyme-producing
ceftazidime-resistant Enterobacter spp., Citrobacter freundii, and some Serratia
spp.; 3) ceftazidime- and imipenem-resistant Pseudomonas aeruginosa; and 4) some
Streptococcus spp. with elevated penicillin MICs. Documented in vitro study
results using 1997 gram-negative blood stream infection isolates indicate a wider
spectrum and a two- to fourfold greater potency for meropenem compared with
imipenem. This was especially true for P. aeruginosa where 93.4% of strains were
susceptible to meropenem (84.1% for imipenem). Also among over 30,000 reported in
vitro meropenem results from the United States and Europe, 90.6% of gram-positive
cocci and 99.1% of anaerobes were inhibited at < or = 4 microg/ml. Over 90% of
ceftazidime-resistant blood stream infection strains were meropenem susceptible,
a rate greater than those of imipenem, ciprofloxacin, and gentamicin. As the
clinical utility of many contemporary antimicrobial agents is challenged by
emerging resistance, the carbapenems (meropenem, imipenem) appear positioned for
a greater role in the treatment of infections in hospitalized patients.
PMID- 9635914
TI - Clinical strategies for serious infection: a North American perspective.
AB - In the United States, as in Europe, clinical strategies for serious infection are
being increasingly driven by growing numbers of cephalosporin-resistant and
multiresistant gram-negative bacilli. In a survey of nearly 400 hospital
intensive care units in North America, resistance rates of Klebsiella to third
generation cephalosporins increased (from 3.6 to 14.4%) between 1990 and 1993.
Resistance rates in Enterobacter are even higher, approaching 40%. Much of this
resistance, which is due mainly to production of type-1 and extended spectrum
beta-lactamases, appears to have arisen through overuse of third-generation
cephalosporins and from poor hand-washing practices. In some American cities, a
major reservoir of resistant organisms are nursing homes, where there is evidence
of overuse of oral antibiotics. Currently, the most reliable agents available for
the treatment of resistant gram-negative pathogens are the carbapenems,
imipenem/cilastatin and meropenem, and the aminoglycoside, amikacin. A recent
clinical study of meropenem monotherapy in patients with nosocomial pneumonia
showed statistically significantly better clinical and microbiologic outcome
compared with a standard regimen of ceftazidime plus tobramycin. The enhanced in
vitro activity of meropenem against a number of key organisms may have been
responsible for the superior results. Although the newer cephalosporins, cefepime
and cefpirome, show greater stability to chromosomal type-1 beta-lactamases than
ceftazidime, they have variable activity against extended spectrum beta-lactamase
producers and can be rendered ineffective by permeability changes which occur in
certain organisms. Carbapenems, on the other hand, possess good activity against
virtually all of the pathogens which produce the clinically important beta
lactamases, and represent a reliable option for treatment.
PMID- 9635915
TI - Clinical strategies for serious infection: a European perspective.
AB - Antimicrobial resistance in nosocomial isolates is of increasing concern to the
clinician, particularly in intensive care units. With more expensive drugs and
prolonged periods of hospitalization required, resistance can result in increased
healthcare costs. For the patient, infection with multiply resistant strains of
bacteria is associated with high mortality rates. This review focuses on the
prevalence of nosocomial infections throughout Europe, with particular emphasis
on the prevalence of resistance to common antimicrobial agents. The beta-lactams
are the most frequently prescribed antimicrobials, and the growing importance of
extended spectrum beta-lactamases and the hyperproduction of chromosomal beta
lactamase by stably derepressed mutants in the development of microbial
resistance are discussed. Given that the most common reason for modification of
an initial empiric antibiotic treatment is the isolation of microorganisms not
susceptible to the initial choice of treatment, the results from two European
multicenter trials comparing the efficacy of the carbapenems, meropenem, and
imipenem/cilastatin, for the treatment of serious nosocomial infections, are
appraised. In light of these results, it can be concluded that the carbapenems
are effective as initial empiric monotherapy for nosocomial infections because of
their broad spectrum of efficacy and stability to beta-lactamases.
PMID- 9635916
TI - Selecting therapy for serious infections in children: maximizing safety and
efficacy.
AB - Serious infections in children represent unique challenges for the treating
physician. For the pediatric patient, considerations of drug toxicity are
especially critical to avoid potential long-term complications of therapy. There
are several advantages associated with using single, broad-spectrum, empiric
antibiotic therapy, including reduced potential for drug-mediated toxicity or
drug interactions and facilitation of home therapy. Of the antibiotics available
for monotherapy, the carbapenems have the broadest spectrum of activity. However,
a major obstacle toward the use of the carbapenems in pediatrics has been the
risk of seizures occurring during therapy with imipenem/cilastatin. In clinical
studies of meningitis and other infections in children, no drug-related seizures
were reported when treated with the carbapenem meropenem. Meropenem monotherapy
has been shown to be similar to ceftriaxone- and cefotaxime-based single or
multiple antibiotic regimens, in terms of clinical and microbiologic efficacy and
tolerability. Thus, meropenem represents a favorable treatment choice for the
seriously ill child, either as empiric monotherapy or as definitive therapy of
polymicrobial or nosocomial infections.
PMID- 9635917
TI - Expanding the options for risk-based therapy in febrile neutropenia.
AB - Fever in neutropenic cancer patients is often due to the development of an
infection. The standard management of febrile neutropenic patients involves the
administration of empiric, hospital-based, parenteral antibiotic therapy.
Although this treatment strategy has evolved from experience in high-risk
patients with hematological malignancies, in whom bacterial infection can result
in substantial morbidity and mortality, it has been adopted for all patients with
febrile neutropenia, largely because of the inability of clinicians to reliably
distinguish between patients who are at high risk for developing such
morbidity/mortality and those who are not. The development of risk-assessment
models has facilitated the recognition of high-, moderate-, and low-risk
subgroups among febrile neutropenic patients and allows the administration of
outpatient antibiotic therapy to the moderate- and low-risk groups, with the same
degree of efficacy and safety as hospital-based therapy. Monotherapy with the
carbapenems (imipenem/cilastatin and meropenem), with their broad spectrum of
activity and established efficacy in high-risk patients, represents realistic
options for risk-based treatment of febrile neutropenic patients within and
outside the hospital setting.
PMID- 9635918
TI - Oral idarubicin and cyclophosphamide for metastatic breast cancer in elderly
patients.
AB - The authors treated 39 heavily pretreated breast cancer patients, median age 72,
with a combined oral regimen featuring idarubicin and cyclophosphamide,
administered without hospitalization in cycles repeated every 4 weeks for a total
not to exceed idarubicin 400 mg/m2. Treatment was remarkably well tolerated, with
generally mild hematological toxicity and only one discontinuation caused by
severe neutropenia; non-hematologic toxicity consisted mainly of moderate nausea
and vomiting in fewer than half the cycles, and hair loss of various severity in
the majority of patients. Therapeutic results were graded as partial responses
(13 cases), no change (NC; 11 cases) or progressive disease (11 cases) for a
response rate of 37.2% (95% CI: 21.1-53.1%). The authors single out the NC issue
as being of special interest, its mere occurrence being rewarding in the
circumstance and its duration in excess of 5 months (seen in six cases) almost
equivalent to therapeutic success.
PMID- 9635919
TI - Oxaliplatin combined to 5-fluorouracil and folinic acid: an effective therapy in
patients with advanced colorectal cancer.
AB - Patients with colorectal carcinoma progressing after a 5-fluorouracil (5-FU)
containing regimen were eligible. One treatment cycle consisted of repeated
administrations of 5-FU combined to folinic acid for six times and to oxaliplatin
for three times over 50 days. 5-FU was given at the dose of 2.6 g/m2 as a
continuous infusion over 24 h on days 1, 8, 22, 29 and 43 preceded by i.v.
folinic acid (FA) at a dose of 500 mg/m2 over 1 h. Oxaliplatin was given 1 h
after 5-FU at the dose of 130 mg/m2 over a 2 h infusion on days 1, 22 and 43. A
total of 37 patients were treated according to this schedule. The rates of
objective responses after the first and second treatment cycles were 28 and 17%,
respectively, with rates of tumor growth control, i.e. including the
stabilizations, of 55 and 28%. The median duration of response was 10 months and
the median duration of stabilizations was 6 months. The median survival time from
initiation of oxaliplatin-containing therapy is 10 months (2-28+). The median
survival time from the diagnosis of metastatic disease is 24 months (2-40+). The
main toxicities were leucopenia, diarrhea, fatigue and paresthesias. The
combination of 5-FU/FA/oxaliplatin was well tolerated and appears as a meaningful
therapy after failure of a previous 5-FU-containing treatment.
PMID- 9635920
TI - Phase II study of paclitaxel in pretreated advanced gastric cancer.
AB - Patients with advanced gastric cancer unresponsive or progressing after PELF
chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received
paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six
patients entered the study, and all of them were evaluable for response and
toxicity. Toxicity was mild: apart from alopecia, grade 3 toxicities were
leukopenia and thrombocytopenia in six patients, and grade 2 neurotoxicity in
seven patients. Eight patients (22.2%, 95% CI: 9-35%) achieved an objective
response, with a median duration of 5 months. Median survival time for all
patients was 8 months. In 16 of 36 patients (44%), treatment determined a
significant relief of symptoms. Out-patient paclitaxel given over 3 h may be
effective as salvage treatment in patients with advanced gastric cancer
refractory to first line chemotherapy.
PMID- 9635921
TI - Elevated expression of S100P, CAPL and MAGE 3 in doxorubicin-resistant cell
lines: comparison of mRNA differential display reverse transcription-polymerase
chain reaction and subtractive suppressive hybridization for the analysis of
differential gene expression.
AB - Subtractive suppressive hybridization (SSH) and mRNA differential display reverse
transcription-polymerase chain reaction (DDRT-PCR) were compared for their
ability to detect the expression of drug-resistance associated genes in a
doxorubicin-resistant and -sensitive colon carcinoma cell line (LoVo H67P). The
expression pattern of more than 9000 bands obtained by DDRT-PCR were identical in
both cell lines by more than 95%. Of the remaining differentially expressed DDRT
PCR products, 21 cDNA fragments were further analyzed after cloning. A total of
210 clones were sequenced resulting in 40 different sequences of which only five
were differentially expressed as revealed by Northern blot analysis. SSH, on the
other hand, resulted in 30 different sequences of 37 clones analyzed. Thirteen of
30 sequences (43%) could be identified by databank analysis (excluding expressed
sequence tags) in contrast to nine of 40 clones (23%) obtained by DDRT-PCR. Of
the clones identified by SSH, 60% exhibited a differential expression comparing
the doxorubicin-resistant and -sensitive cell line, respectively, as compared to
only 13% of the DDRT-PCR derived clones. The application of SSH resulted in the
identification of differentially expressed genes in three doxorubin-resistant
cell lines (LoVo DxR, ARH D60 and KB-V1) as compared to the sensitive parental
cell lines. A significant higher expression of S100P, a protein involved in
calcium metabolism, as well as MAGE 3 (melanoma antigen gene) was found in the
resistant cell lines using this methodology. The expression of CAPL, a second
protein involved in calcium metabolism, was only moderately elevated in the
doxorubicin-resistant cells. We found that subtractive suppressive hybridization
proved to be a more rapid and reliable method for the detection of differentially
expressed mRNAs in our system.
PMID- 9635922
TI - Enhancement of cytotoxicity by electropermeabilization: an improved method for
screening drugs.
AB - Electropermeabilization (EPN), also termed electroporation, is a physical method
to overcome the barrier of the cell membrane by applying short and intense
electric pulses. It is the basis for a new cancer treatment modality,
electrochemotherapy, where uptake of chemotherapeutics is enhanced by EPN.
Preclinical and clinical trials have shown that application of electric pulses in
vivo is feasible and that electrochemotherapy is highly efficient. The aim of
this study was to develop an improved method of screening drugs on
electropermeabilized versus non-electropermeabilized cells. In this study we
describe an easy protocol which gives high cell viability, good reproducibility
and a high rate of cell permeabilization. Cell cytotoxicity is simply determined
by the MTT assay. Cell death due to the EPN procedure was less than 4% and more
than 90% of cells were permeabilized. For daunorubicin, doxorubicin, etoposide
and paclitaxel, no effect of EPN was found. For carboplatin and cisplatin the
effect of EPN was a factor 3 and 2.3, respectively, on the IC50 (inhibitory
concentration 50%). For bleomycin we found a dramatic effect of EPN of the
magnitude of a factor 300 on the IC50. In conclusion, we have established a new,
easy and reliable protocol to test new drugs for cytotoxicity with or without the
limitations of the cell membrane. Our data support the role of bleomycin as the
drug of choice for electrochemotherapy.
PMID- 9635923
TI - Antiproliferative effects of recombinant human bone morphogenetic protein-2 on
human tumor colony-forming units.
AB - Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal
osteoblasts. BMP-2 is structurally related to transforming growth factor-beta
which inhibits cell proliferation and enhances apoptosis. A recent study has
shown the presence of BMP-2 receptors on several cancer cell lines. In this
study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can
modulate the proliferation of human tumor colony-forming units taken from 113
patients. Tumor cells were cultured in soft agar and continuously exposed to
three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the
capillary cloning system. There were 65 evaluable specimens, including 17 breast
cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate
cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A
significant inhibition (50% or less survival of tumor colony-forming units) was
seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small
cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A
concentration-response relationship was observed (p<0.001 by Mantel-extension
test). The results of this study encourage further evaluation of the
antiproliferative effects of rhBMP-2 against human cancers.
PMID- 9635924
TI - Murine peritoneal macrophages treated with cisplatin and interferon-gamma undergo
NO-mediated apoptosis via activation of an endonuclease.
AB - We investigated whether murine peritoneal macrophages treated with cisplatin or
interferon (IFN)-gamma alone, or in combination, could undergo apoptosis, and
whether this results either from the cytotoxic effect of the activating agents or
indirectly in an autocrine manner by the cytotoxic molecules released by them
upon activation. Our data suggest that cisplatin, which has been shown to induce
apoptosis in a number of normal as well as tumor cell types, did not induce
apoptosis in murine peritoneal macrophages nor was apoptosis caused by IFN-gamma.
However, combined treatment with cisplatin and IFN-gamma induced apoptosis in
macrophages as studied by percent DNA fragmentation assay, qualitative analysis
of DNA on agarose gel electrophoresis, and morphological and nuclear alterations
studied by phase contrast and fluorescence microscopy. The factor responsible for
inducing apoptosis in macrophages was found to be a higher concentration of NO
produced by them upon activation with cisplatin and IFN-gamma. Macrophages
treated with cisplatin or IFN-gamma alone produced a low level of NO and did not
undergo apoptosis. The inhibitor of NO synthase, L-NMMA, prevented apoptosis in
macrophages treated with cisplatin and IFN-gamma, suggesting the involvement of
NO in the induction of apoptosis in macrophages. The role of NO in inducing
apoptosis in macrophages was further confirmed by the observation that direct
treatment with sodium nitroprusside, a NO donor, resulted in apoptosis in
macrophages. We have also shown that NO-induced apoptosis in macrophages
activated with cisplatin and IFN-gamma requires activation of an endonuclease, as
the endonuclease inhibitor, aurine tricarboxylic acid, prevented apoptosis in
them.
PMID- 9635925
TI - Combination therapy of active hexose correlated compound plus UFT significantly
reduces the metastasis of rat mammary adenocarcinoma.
AB - Synergistic effects of active hexose correlated compound (AHCC) extracted from
mushroom on the treatment with UFT against mammary adenocarcinoma, SST-2 cells,
in congenitally T cell-depressed spontaneously hypertensive rats (SHR) were
observed. AHCC plus UFT had slight but significant effects on the growth of
primary tumors. Pulmonary metastases were not inhibited by the treatment with
AHCC plus UFT, whereas metastases to axillary lymph nodes (LN) were obviously
inhibited. Combination of AHCC plus UFT showed similar synergistic anti
metastatic effects in SHR rats with accelerated pulmonary metastases following
the surgical removal of the primary tumors. In vitro studies demonstrated that
AHCC plus UFT enhanced the NK cell activity in tumor-bearing rats, whereas UFT
alone depressed the NK cell activity. AHCC plus UFT also enhanced the NO
production and cytotoxicity of peritoneal macrophages. In addition, AHCC restored
the suppressed mRNA expression of interleukin-1alpha and tumor necrosis factor
alpha induced by the chemotherapy. Taken together, the combination of AHCC plus
UFT brought about good therapeutic effects not only on primary tumor growth but
also on reducing metastasis and these effects were mediated by host immunity
which was restored or activated by AHCC. AHCC may be a good candidate for a
biological response modifier.
PMID- 9635926
TI - Additive effects of medroxyprogesterone acetate and 5-fluorouracil derivative on
7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.
AB - Chronic oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in
combination with uracil suppressed thymidylate synthetase (TS) gene expression
followed by reduction of TS activity in rat mammary tumors induced with 7,12
dimethylbenz[a]anthracene. Addition of medroxyprogesterone acetate (MPA) to the
anticancer drug caused an additional decrease in TS and thymidine kinase
activities in the tumor growth and restoration of bone loss. These results
suggest that the simultaneous administration of MPA and anticancer drugs causes
increased inhibition of mammary tumor growth and also diminishes the bone loss.
PMID- 9635927
TI - Paclitaxel plus ifosfamide in advanced ovarian cancer: results of a phase I
study.
AB - Patients with advanced ovarian carcinoma and an inadequate response to first-line
platinum-based combination chemotherapy (CTX) have a very poor prognosis and
effective salvage regimens are clearly needed. This phase I study was performed
in order to determine the maximum tolerable dose (MTD) and dose-limiting toxicity
(DLT) of the combination paclitaxel (P) and ifosfamide (IFO). After
premedication, patients received P as a 3 h i.v. infusion on day 1; IFO was given
as 1 h i.v. infusion with the standard dose of mesna i.v. on days 2-5, q day 22.
The following dose levels (dl) were investigated: (mg/m2/day) dl1, P 135/IFO
1500; dl2, P 135/IFO 2000; dl3, P 175/IFO 2000; and dl4, P 175/ IFO 1500.
Eighteen patients with advanced ovarian cancer entered this trial. In eight
patients treated with an IFO dose of 2000 mg/m2 during dl2 and 3, two required
treatment interruptions because of CNS toxicity CTC grade 3 and one patient
experienced nephrotoxicity CTC grade 3, Therefore the MTD of IFO used in
combination with P and given over 4 days is reached with 2000 mg/m2/day. In the
fourth dl we escalated the P dose up to 175 mg/m2, reduced the IFO dose to 1500
mg/m2 and treated an additional five patients. No DLT occurred at that dl.
Objective responses were observed at all dls. The combination of P and IFO is
feasible and active in pretreated advanced ovarian carcinoma. dl4 is the
recommended dose for phase II trials.
PMID- 9635928
TI - A pilot study of fiberscopy-guided local injection of anti-cancer drugs bound to
carbon particles for control of rectal cancer.
AB - Rectal cancer patients with contra-indicatory risks may not be able to undergo
surgery. In these cases the preferred treatment is chemotherapy. The present
dosage formulation, consisting of an anti-cancer drug bound to activated carbon
particles, was designed to deliver the anti-cancer drug at high concentration
selectively to the injection site as well as to the regional lymph nodes and to
improve survival of mice bearing cancer with nodal metastases, as compared to the
same dose of aqueous anti-cancer drug in animal experiments. The present clinical
trial includes two patients with histologically confirmed adenocarcinoma of the
rectum and who had risks contra-indicating surgery. Carbon particles adsorbing
anti-cancer drugs totaling 400 mg of methotrexate and 32 mg of mitomycin C in one
patient and 100 mg of methotrexate and 8 mg of mitomycin C in another patient
were injected into the cancer tissue under guidance of a colono-fiberscope. The
rectal cancers were successfully reduced in size and controlled over 2 years or 6
months until the patients died from other causes. Side effect was mild. Local
injection of this dosage formulation will be useful for the control of rectal
cancer in patients who cannot undergo surgery.
PMID- 9635929
TI - Air pollution and asthma--fact or artifact? A plea for inclusion of objective
measures in environmental epidemiology.
PMID- 9635930
TI - Respiratory symptoms of primary school children living in a petrochemical
polluted area in Taiwan.
AB - In 1994-1995 a cross-sectional epidemiological study investigating the
respiratory health of school children in two Taiwan areas was conducted; one area
was located in a region with petrochemical manufacturing complexes (Linyuan), and
the other was situated in a reference area with no local industrial emissions
(Taihsi). All primary school children residing in the two areas were involved in
the study. Four hundred seventy children were studied in the area with high
exposure to industrial emissions, and 611 children lived in the reference area.
Respiratory health was assessed by evaluation of the children's respiratory
symptoms and illnesses, using a parent-completed questionnaire. Particulates,
sulfur dioxide (SO2), nitrogen dioxide (NO2), and acid aerosols levels were
significantly higher in the exposed area than in the reference area. The school
children in the petrochemical area had significantly more upper respiratory
symptoms and asthma compared with the children living in the control area.
Although the association with known petrochemical air pollution is suggestive,
this cross-sectional study cannot confirm a causal relation and further studies
are needed.
PMID- 9635931
TI - Stenotrophomonas maltophilia in cystic fibrosis: incidence and prevalence.
AB - Stenotrophomonas maltophilia (SM) was recovered from 211 of 773 cystic fibrosis
(CF) patients followed for at least one year, and seen between 1982 and 1994.
Yearly prevalence (5.6% to 8.7%) and incidence rates (1.6% to 5.7%) showed no
trends. SM persistence varied greatly and was unlike that of Pseudomonas
aeruginosa. Fifty percent of SM-positive patients had only one positive culture
and only 24 (11%) remained chronically infected. Although SM-positive patients
were more likely to be hospitalized than SM-negative patients, for 55% of SM
positive patients, acquisition did not appear to follow hospitalization. Of 40 SM
positive patients who had a CF sibling, only 10 siblings were ever culture
positive. When stratified by FEV1, the two-year survival for SM-positive with
mild/moderate disease (98%) and severe disease (78%) was similar to that of our
SM-negative patients. Five-year survival was only 40% for SM-positive patients
with initially severe pulmonary status, compared with 72% for the SM-negative
patients. Seventy percent of the original SM isolates were panresistant
(susceptible to no more than one antimicrobial agent). Ten years later,
panresistance was 84%. Despite our reassuring experience with SM, including lack
of sibling concordance, the fact that the majority of our patients had no
hospital exposure prior to acquisition, the high incidence of transient
infection, and the seemingly unaffected two-year survival, there are insufficient
data to definitively conclude that segregation of these patients would be
beneficial. The increasing prevalence of multiply resistant gram-negative
pathogens in CF patients suggests the need for continued caution with any
panresistant pathogen.
PMID- 9635932
TI - Parental attitudes toward infant pulmonary function testing.
AB - Infant pulmonary function tests (PFTs) have proven increasingly popular and
useful for clinical and research purposes. Informed consent requires accurate
information on side effects. Our aim was to quantify minor side effects from a
parental point of view by means of a questionnaire. The parents of 97 infants
attending for PFTs were asked to complete a simple questionnaire. Eighty-one
parents (84%) returned the questionnaire. Forty-one percent felt that their
infants were not troubled by the process of administering the sedative chloral
hydrate, whereas 55% suffered mild to moderate distress. In contrast, 94% of
infants were not distressed by the actual PFTs. Similarly, 46% of parents were
not distressed by the administration of sedative to their infant, with 49%
expressing distress to a mild or moderate degree. Although 73% of parents were
not distressed by watching their infants undergo the PFTs, 27% were to a mild to
moderate degree. Seventy-three percent of infants were untroubled on waking.
Seventy percent of infants had a good nights sleep after the PFTs. The vast
majority of parents (94%) were happy to recommend that others allow their infants
to undergo similar testing. We noted that most problems caused by infant PFTs
relate to the administration of the sedative. Most infants awake from the tests
not distressed and sleep normally the following night.
PMID- 9635933
TI - Effect of salmeterol treatment on nitric oxide level in exhaled air and dose
response to terbutaline in children with mild asthma.
AB - The aim of this study was to investigate whether regular treatment with inhaled
salmeterol modifies the dose-response curve to the inhaled short-acting beta2
agonist terbutaline or affects the concentration of nitric oxide (NO) in exhaled
air of children with asthma. Twenty-two children aged 7 to 15 years (mean = 11.6
years) with mild asthma were treated with inhaled 50 microg salmeterol twice
daily or placebo for 3 weeks in a randomized double-blind cross-over study. These
treatments were followed by treatment with inhaled 200 microg budesonide twice
daily for 3 weeks. On the last day of each period, NO level was measured in
exhaled air and a cumulative dose-response experiment with terbutaline
(cumulative dose: 1,475 microg) was performed. Baseline lung functions after
salmeterol treatment were significantly higher than baseline after placebo (P +
0.05). Salmeterol treatment flattened out the dose-response curve to terbutaline
such that higher doses of terbutaline were required to produce the same degree of
bronchodilation (ED50 for FEV1 was increased by an estimated factor of 70 (95%
CI: 0.8-6307) and ED50 for FEF25-75 by a factor of 41 (95% CI: 6.7-254); P <
0.05). NO levels were unaffected by salmeterol treatment (12.7 ppb; placebo =
10.7 ppb), but were significantly reduced during budesonide therapy (5.2 ppb; P <
0.001). The corresponding maximal NO levels were 19.5 (placebo), 22.9
(salmeterol), and 9.4 ppb (budesonide). We conclude that 3 weeks treatment with
salmeterol does not affect NO levels in exhaled air, but it significantly changes
the dose-response curve to terbutaline.
PMID- 9635934
TI - Specific airway resistance, interrupter resistance, and respiratory impedance in
healthy children aged 2-7 years.
AB - We report data on respiratory function in healthy children aged 2-7 years in whom
we measured respiratory resistance by the interrupter technique (Rint); total
respiratory impedance (Zrs), respiratory resistance (Rrs), and reactance (Xrs) by
the impulse oscillation technique; and specific airway resistance (sRaw) by a
modified procedure method in the whole body plethysmograph. Measurements were
attempted in 151 children and were successfully obtained in 121 children with a
mean (SD) age of 5.3 (1.5) years; no measurements were possible in 30 children
(mean age 3 (0.9) years). The repeatability of measurements was independent of
the age of the subjects, and the within-subject coefficient of variation was
11.1%, 8.1%, 10.8%, and 10.2% for sRaw, Rint, Zrs, and Rrs at 5 Hz (Rrs5),
respectively. All lung function indices were linearly related to age, height, and
weight. A significant negative correlation with age, height, and weight was found
for Rint, Zrs, and Rrs5. Xrs5 was positively correlated to age and body size. The
mean values of Rint, Rrs5, Xrs5, and Zrs in children younger and older than 5
years were 1.04, 1.38, -0.5, and 1.48 kPa x L(-1) x s and 0.9, 1.18, -0.37, and
1.23 kPa x L(-1) x s, respectively. sRaw showed no significant correlation with
body size or age and the mean sRaw in children younger and older than 5 years was
1.09 and 1.13 kPa x s, respectively. None of the indices of respiratory function
differed between boys and girls. Xrs and Rrs exhibited a significant frequency
dependence in the range of 5-35 Hz. The techniques applied in this study require
minimal cooperation and allow measurement of lung function in 80% of our
population of awake young children. Further studies are needed to evaluate the
potentials of the presently established reference values for clinical and
epidemiological purposes.
PMID- 9635935
TI - Environmental effects on pulmonary mechanics and the response to inhaled
methacholine.
AB - To investigate the role of environmental exposure from birth on airway and lung
parenchymal responsiveness to inhaled methacholine (Mch), three litters of
puppies (n = 14) were studied when 8-10 weeks of age. Two litters, one mongrel (n
= 7) and one foxhound-beagle cross (n = 3), were born and raised in a clean
animal house environment (clean mongrels and clean cross, respectively). Another
litter of mongrels was born (n = 4) and raised in an external environment
(external mongrels), exposed to normal rural environmental contaminants. Animals
were studied open-chested with alveolar capsules used to partition mechanics into
airway and parenchymal components. Lung mechanics were measured after abrupt flow
interruptions. The animals born and raised in the external environment were
significantly more responsive to inhaled Mch than those born and raised in the
clean environment. This finding was true for both airway and parenchymal
responsiveness. The group mean effective dose of Mch that produced a doubling of
airway resistance (ED200Raw) for the external mongrel group was 4.40 mg/ml
compared with 19.44 mg/ml for the clean mongrel group and 16.34 mg/ml for the
clean cross group (P < 0.02). The group mean effective dose of Mch that produced
a doubling of pressure difference in airways after the initial rapid rise in
airway pressure (ED200Pdif) for the external mongrel group was 0.79 mg/ml
compared with 3.90 mg/ml for the clean mongrel group and 10.78 mg/ml for the
clean cross group (P < 0.01). Generalized linear modeling analysis showed that
both "environment" and "breed" were significant factors in determining ED200Pdif,
but only "environment" significantly influenced ED200Raw. In summary, the present
study has demonstrated that the environment in which an animal is born and raised
can influence lung mechanics and responsiveness to methacholine. This finding is
particularly true for the lung parenchyma.
PMID- 9635936
TI - Transcutaneous oxygen tension measurements during methacholine challenge of
prematurity in infants with chronic lung disease.
AB - Chronic lung disease (CLD) of prematurity may be caused by a number of insults
during mechanical ventilation, including barotrauma and hyperoxia. To evaluate
bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we
measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine
inhalation challenge. Twelve infants with CLD and 22 age-matched children without
respiratory diseases were enrolled in this study (ages--5 to 36 months; mean age-
16.2 months). Serial doses of methacholine were doubled until a 10% decrease in
tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by
the time tcPO2 had been reached (Dmin-PO2) was considered to represent the dose
at which reactivity to methacholine (RO2meth) had occurred. In the CLD group,
Dmin-PO2 (3.50 +/- 0.1 log x milli-units) was significantly lower than in the
preterm control infant group (4.31 +/- 0.2 log x milli-units) and the term infant
group (4.21 +/- 0.1 log x milli-units) (P = 0.004, P < 0.001). Dmin-PO2 in the
preterm control infant group was not significantly different than in the term
infant group (P > 0.5). These results suggest that infants who require additional
therapeutic oxygen and mechanical ventilation during the early months of life are
at risk of developing early-onset, long-lasting respiratory disease that is
related to an acquired BHR.
PMID- 9635937
TI - Hypoxemia due to the obstruction of a right tracheal bronchus by an endotracheal
tube in a child with left bronchial foreign body aspiration.
PMID- 9635938
TI - Fatal desquamative interstitial pneumonia associated with proven CMV infection in
an 8-month-old boy.
PMID- 9635939
TI - Braided bronchus: a previously undescribed airway anomaly.
AB - Infants with congenital heart disease frequently experience recurrent
atelectasis, in many cases associated with anomalous branching of the bronchial
tree. The bridging bronchus has been well described and has been associated with
both left-sided obstructive lesions and a sling-like left pulmonary artery. We
describe a similar, though distinct airway anomaly, the "braided bronchus,"
associated with a bridging bronchus in a child with coarctation of the aorta and
recurrent atelectasis. Methods used to delineate the "braided bronchus" are
described.
PMID- 9635940
TI - Nuclear rumblings in the East.
PMID- 9635941
TI - J-curve not burned off by HOT study. Hypertension Optimal Treatment.
PMID- 9635942
TI - Transplant tolerance: will genes protect the graft?
PMID- 9635943
TI - Prediction of recovery from post-traumatic vegetative state.
PMID- 9635945
TI - How many neutrophils are enough?
PMID- 9635944
TI - Patients' records on the Internet: a boost for evidence-based medicine.
PMID- 9635946
TI - Improved prognosis for biomarkers in breast cancer.
PMID- 9635947
TI - Effects of intensive blood-pressure lowering and low-dose aspirin in patients
with hypertension: principal results of the Hypertension Optimal Treatment (HOT)
randomised trial. HOT Study Group.
AB - BACKGROUND: Despite treatment, there is often a higher incidence of
cardiovascular complications in patients with hypertension than in normotensive
individuals. Inadequate reduction of their blood pressure is a likely cause, but
the optimum target blood pressure is not known. The impact of acetylsalicylic
acid (aspirin) has never been investigated in patients with hypertension. We
aimed to assess the optimum target diastolic blood pressure and the potential
benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.
METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years)
with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg
(mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264
patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85
mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with
the addition of other agents, according to a five-step regimen. In addition, 9399
patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra)
and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was
reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or
=85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence
of major cardiovascular events occurred at a mean achieved diastolic blood
pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at
86.5 mm Hg. Further reduction below these blood pressures was safe. In patients
with diabetes mellitus there was a 51% reduction in major cardiovascular events
in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for
trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15%
(p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on
stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight
in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups,
respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in
patients with hypertension was associated with a low rate of cardiovascular
events. The HOT Study shows the benefits of lowering the diastolic blood pressure
down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major
cardiovascular events with the greatest benefit seen in all myocardial
infarction. There was no effect on the incidence of stroke or fatal bleeds, but
non-fatal major bleeds were twice as common.
PMID- 9635948
TI - Prediction of recovery from post-traumatic vegetative state with cerebral
magnetic-resonance imaging.
AB - BACKGROUND: The early post-traumatic vegetative state (VS) is compatible with
recovery. Various clinical and laboratory tests have failed to predict recovery
so we assessed the value of cerebral magnetic-resonance imaging (MRI) in
prediction of recovery. METHODS: 80 adult patients in post-traumatic VS had
cerebral MRI between 6 weeks and 8 weeks after injury. MRIs were reviewed by
three neuroradiologists for the number, sizes, and location of brain lesions.
Three neurologists assessed the patients at the time of MRI and at 2 months, 3
months, 6 months, 9 months, and 12 months after injury using the Glasgow Outcome
Scale. FINDINGS: At 12 months, 38 patients had recovered while 42 patients
remained in the VS. The demographic characteristics and causes and severity of
injury were similar in patients in persistent VS (PVS) and those who recovered
(NPVS). An average of 6.1 different brain areas were injured in patients in PVS
compared with 4.6 areas in patients who had NPVS. Patients in PVS revealed a
significantly higher frequency of corpus callosum, corona radiata, and
dorsolateral brainstem injuries than did patients who recovered. Logistic
regression analysis showed that corpus callosum and dorsolateral brainstem
injuries were predictive of non-recovery. The adjusted odds ratios for non
recovery of patients with a corpus callosum lesion and dorsolateral brainstem
injury were 213.8 (95% CI 14.2-3213.3), and 6.9 (11-42.9), respectively. In
contrast, clinical characteristics, such as initial score on the Glasgow Coma
Scale, age, and pupillary abnormalities failed to predict recovery.
INTERPRETATION: Cerebral MRI findings in the subacute stage after head injury can
predict the outcome of the post-traumatic VS. Corpus callosum and dorsolateral
brainstem lesions are highly significant in predicting non-recovery.
PMID- 9635949
TI - Low plasma concentrations of interleukin 10 in severe malarial anaemia compared
with cerebral and uncomplicated malaria.
AB - BACKGROUND: Severe anaemia is a major complication of malaria but little is known
about its pathogenesis. Experimental models have implicated tumour necrosis
factor (TNF) in induction of bone-marrow suppression and eythrophagocytosis.
Conversely, interleukin 10 (IL-10), which mediates feed-back regulation of TNF,
stimulates bone-marrow function in vitro and counteracts anaemia in mice. We
investigated the associations of these cytokines with malarial anaemia. METHODS:
We enrolled 175 African children with malaria into two studies in 1995 and 1996.
In the first study, children were classified as having severe anaemia (n=10),
uncomplicated malaria (n=26), or cerebral anaemia (n=41). In the second study,
patients were classified as having cerebral malaria (n=33) or being fully
conscious (n=65), and the two groups were subdivided by measured haemoglobin as
normal (>110 g/L), moderate anaemia (60-90 g/L), and severe anaemia (<50 g/L). IL
10 and TNF concentrations were measured by ELISA in plasma samples from all
patients. FINDINGS: IL-10 concentrations were significantly lower in patients
with severe anaemia than in all other groups. In 1995, geometric mean plasma IL
10 in patients with severe anaemia was 270 pg/mL (95% CI 152-482) compared with
725 pg/mL (465-1129) in uncomplicated malaria and 966 pg/mL (612-1526) in
cerebral malaria (p<0.03). In 1996, fully conscious patients with severe anaemia
also had significantly lower IL-10 concentrations than all other groups,
including cerebral-malaria patients with severe anaemia and all patients with
moderate anaemia (p<0.001). In both studies, TNF concentrations were
significantly higher in cerebral malaria than in fully conscious patients
(p<0.01). By contrast, the ratio of TNF to IL-10 was significantly higher in
fully conscious patients with severe anaemia than in all other groups (p<0.001).
INTERPRETATION: Our findings identify severe malarial anaemia as a distinct
disorder in which insufficient IL-10 response to high TNF concentrations may have
a central role.
PMID- 9635950
TI - Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in
chronic hepatitis and cirrhosis with hepatitis-C-virus infection.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) commonly develops in patients with
chronic hepatitis or cirrhosis of the liver caused by hepatitis-C-virus (HCV)
infection. We prospectively studied whether irregular regeneration of hepatocytes
is a risk factor for HCC in these patients. METHODS: 242 patients were enrolled
after liver biopsy and followed up by ultrasonographic scanning every 3 months.
We examined age, sex, platelet count, the diagnosis of cirrhosis or chronic
hepatitis, liver-cell dysplasia, and irregular regeneration. We classified
irregular regeneration as slight or severe, based on histological expression of
pleiomorphism, anisocytosis, bulging, and map-like distribution of hepatocytes.
FINDINGS: 37 of 63 patients with cirrhosis and 26 of 179 with chronic hepatitis
were judged to have severe irregular regeneration. HCC was diagnosed in 33 of 63
patients with cirrhosis (29 had severe irregular regeneration) and 12 of 179
patients with chronic hepatitis (11 had severe irregular regeneration) during
mean follow-up of 5.5 years (SD 4.1; range 1-16). Multivariate analysis with a
proportional-hazards model showed severe irregular regeneration (relative risk
15.1 [95% CI 5.6-40.7], p<0.0001) and a diagnosis of cirrhosis (3.8 [1.7-8.2],
p=0.0008) to be significant risk factors for HCC. Within the diagnostic
categories, irregular regeneration was also significant (cirrhosis 6.8 [2.1
21.9], p=0.0014; chronic hepatitis 28.5 [2.9-276.4], p=0.0038). INTERPRETATION:
We recommend that liver biopsy to look for irregular regeneration should be done
in patients with HCV-related chronic liver diseases. Those with severe irregular
regeneration should be followed up carefully.
PMID- 9635951
TI - Effect of immunosuppression after cardiac transplantation in early childhood on
antibody response to polysaccharide antigen.
AB - BACKGROUND: Three children who had cardiac transplantation before age 4 years
later presented with recurrent sinopulmonary infection caused by organisms
including Streptococcus pneumoniae, in which capsular polysaccharide plays an
important part, one developed bronchiectasis. We therefore studied responses to
polysaccharide antigen after immunosuppression started in early childhood.
METHODS: Antibodies against pneumococcal and haemophilus polysaccharides, and
total IgG, IgG1, IgG2, and IgA concentrations were measured in 33 cardiac
transplant recipients transplanted before the age 4 years (group 1) and after
that age (group 2). Patients with low pneumococcal and haemophilus antibody
concentrations were immunised with 23 polyvalent pneumococcal and tetanus
haemophilus conjugate vaccines and antibody responses were measured. FINDINGS:
Five patients from group 1 and seven from group 2 were transplanted for
congenital heart disease and ten patients in each group had heart transplants
because of cardiomyopathy; none were asplenic. Group 1 (16 patients) were aged 2
10 years when investigated, group 2 (17 patients), were 6-16 years. Four of 16
patients in group 1 responded to pneumococcal polysaccharide vaccine compared
with 14 of 17 in group 2 (p=0.0016). This difference remained when those in group
1, aged less than 4 years at investigation, were excluded (p=0.0060). Response to
haemophilus-conjugate vaccine was similar in both groups (14 of 16 vs 14 of 17,
p=1.0). Significantly more patients who failed to respond to pneumococcal vaccine
had low IgG2 concentrations (p=0.0269). INTERPRETATION: Children who had a
transplantation and immunosuppression in early childhood before they had
developed antibody responses to pneumococcal polysaccharide, still failed to show
a response when older-ie, when such responses are the norm. Ongoing
immunosuppression prevents the maturation of antipolysaccharide responses leaving
children susceptible to severe and recurrent damaging infection.
PMID- 9635952
TI - A boy with chickenpox whose fingers peeled.
PMID- 9635953
TI - Treatment of neurotrophic keratopathy with substance-P-derived peptide (FGLM) and
insulin-like growth factor I.
PMID- 9635954
TI - Low-dose MDMA ("ecstasy") induces vasopressin secretion.
PMID- 9635955
TI - 5-HT2A promoter polymorphism in anorexia nervosa.
PMID- 9635956
TI - 5-HT2A promoter polymorphism -1438G/A, anorexia nervosa, and obsessive-compulsive
disorder.
PMID- 9635957
TI - Follow-up of ventricular pre-excitation in Japanese schoolchildren.
PMID- 9635958
TI - ABO blood group and inhaled nitric oxide in acute respiratory distress syndrome.
PMID- 9635959
TI - Association at LRP gene locus with sporadic late-onset Alzheimer's disease.
PMID- 9635960
TI - Could lightning injury be magnetically induced?
PMID- 9635961
TI - HIV-1-vaccine-trial go-ahead reawakens ethics debate.
PMID- 9635962
TI - Unravelling the complexities of environmental effects on breast-cancer risk.
PMID- 9635963
TI - The copolymer-1 story so far.
PMID- 9635964
TI - Famine appeals versus long-term aid by the UK.
PMID- 9635966
TI - Canada starts renewed effort against tobacco-industry advertising.
PMID- 9635968
TI - Kidney stones.
PMID- 9635969
TI - What do the basal ganglia do?
AB - We propose that the basal ganglia support a basic attentional mechanism operating
to bind input to output in the executive forebrain. Such focused attention
provides the automatic link between voluntary effort, sensory input, and the
calling up and operation of a sequence of motor programmes or thoughts. The
physiological basis for this attentional mechanism may lie in the tendency of
distributed, but related, cortical activities to synchronise in the gamma (30 to
50 Hz) band, as occurs in the visual cortex. Coherent and synchronised elements
are more effective when convergence occurs during successive stages of
processing, and in this way may come together to give the one gestalt or action.
We suggest that the basal ganglia have a major role in facilitating this aspect
of neuronal processing in the forebrain, and that loss of this function
contributes to parkinsonism and abulia.
PMID- 9635970
TI - Decentralisation and privatisation of long-term care in UK and USA.
PMID- 9635971
TI - Calcium channel blockers and cardiovascular risk in diabetes.
PMID- 9635972
TI - Calcium channel blockers and cardiovascular risk in diabetes.
PMID- 9635973
TI - Internet access to patients' records.
PMID- 9635974
TI - Acellular pertussis vaccines: progress but deja vu.
PMID- 9635975
TI - Micronutrient deficiencies and protein-energy malnutrition.
PMID- 9635976
TI - HIV-1 transmission through artificial insemination.
PMID- 9635977
TI - Isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in
HIV-1 infection.
PMID- 9635978
TI - Increase of allergy in East Germany.
PMID- 9635979
TI - Increase of allergy in East Germany.
PMID- 9635980
TI - NIH follow-up study of women with augmentation mammoplasty: investigator replies.
PMID- 9635981
TI - Gammow bag for acute mountain sickness.
PMID- 9635982
TI - Human-milk lactadherin in protection against rotavirus.
PMID- 9635983
TI - The viable myocardium.
PMID- 9635984
TI - Costs of stenting for acute myocardial infarction.
PMID- 9635985
TI - Coronary microvascular spasm and angina pectoris.
PMID- 9635986
TI - N-methyl-(R)-salsolinol and Parkinson's disease.
PMID- 9635987
TI - Butyrylcholinesterase K: an association with dementia with Lewy bodies.
PMID- 9635988
TI - Harm reduction and needle exchange programmes.
PMID- 9635989
TI - Harm reduction and needle exchange programmes.
PMID- 9635990
TI - Water hyacinths.
PMID- 9635991
TI - Botulinum toxin, a historical note.
PMID- 9635992
TI - Lies, damned lies, and evidence-based medicine.
PMID- 9635993
TI - The questionable role of saturated and polyunsaturated fatty acids in
cardiovascular disease.
AB - A fat diet, rich in saturated fatty acids (SFA) and low in polyunsaturated fatty
acids (PUFA), is said to be an important cause of atherosclerosis and
cardiovascular diseases (CVD). The evidence for this hypothesis was sought by
reviewing studies of the direct link between dietary fats and atherosclerotic
vascular disease in human beings. The review included ecological, dynamic
population, cross-sectional, cohort, and case-control studies, as well as
controlled, randomized trials of the effect of fat reduction alone. The positive
ecological correlations between national intakes of total fat (TF) and SFA and
cardiovascular mortality found in earlier studies were absent or negative in the
larger, more recent studies. Secular trends of national fat consumption and
mortality from coronary heart disease (CHD) in 18-35 countries (four studies)
during different time periods diverged from each other as often as they
coincided. In cross-sectional studies of CHD and atherosclerosis, one group of
studies (Bantu people vs. Caucasians) were supportive; six groups of studies
(West Indians vs. Americans, Japanese, and Japanese migrants vs. Americans,
Yemenite Jews vs. Yemenite migrants; Seminole and Pima Indians vs. Americans,
Seven Countries) gave partly supportive, partly contradictive results; in seven
groups of studies (Navajo Indians vs. Americans; pure vegetarians vs. lacto-ovo
vegetarians and non-vegetarians, Masai people vs. Americans, Asiatic Indians vs.
non-Indians, north vs. south Indians, Indian migrants vs. British residents,
Geographic Study of Atherosclerosis) the findings were contradictory. Among 21
cohort studies of CHD including 28 cohorts, CHD patients had eaten significantly
more SFA in three cohorts and significantly less in one cohort than had CHD-free
individuals; in 22 cohorts no significant difference was noted. In three cohorts,
CHD patients had eaten significantly more PUFA, in 24 cohorts no significant
difference was noted. In three of four cohort studies of atherosclerosis, the
vascular changes were unassociated with SFA or PUFA; in one study they were
inversely related to TF. No significant differences in fat intake were noted in
six case-control studies of CVD patients and CVD-free controls; and neither total
or CHD mortality were lowered in a meta-analysis of nine controlled, randomized
dietary trials with substantial reductions of dietary fats, in six trials
combined with addition of PUFA. The harmful effect of dietary SFA and the
protective effect of dietary PUFA on atherosclerosis and CVD are questioned.
PMID- 9635994
TI - Dietary fats and heart disease--dogma challenged?
PMID- 9635995
TI - Observational research and evidence-based medicine: What should we teach young
physicians?
PMID- 9635996
TI - Correlates of family history of coronary artery disease in children.
AB - The atherosclerotic process begins in childhood but, in general, does not reach
the clinical horizon until after the fifth decade of life, at which point the
best opportunities for prevention and intervention have been lost. In order to
identify children with a high risk of developing coronary artery disease (CAD),
risk factors measured in children that are the most informative indicators of
future risk must be identified. Using a novel analytical strategy that
incorporates a continuum of information about context dependency, we investigated
whether there were significant differences in intermediate biochemical and
physiological traits between children (189 females and 188 males, ages 5-20.5
years) with and without a strong family history of clinically-defined CAD at
three levels of context dependency (coarse grain, medium grain, and fine grain).
In the coarse-grained analysis we tested for differences in mean levels of nine
intermediate traits (lipids, apolipoproteins, blood pressure traits) and indices
of external and internal environmental context (age, body mass index, smoking
status). Female children with a strong family history had higher average levels
for total cholesterol, triglyceride, Apo B, and systolic blood pressure and were
on average older and weighed more than female children with a weak family history
of CAD. Male children with a strong family history of CAD had higher average
levels of triglycerides and were on average older than male children with a weak
family history. In the medium-grained analysis we investigated whether the
regression relationships between each intermediate trait and each measure of
environmental context was significantly different between children with and
without a strong family history of CAD. Our results indicate that children with a
strong family history of CAD have a significantly different relationship between
their intermediate traits and environmental contexts than children with a weak
family history. In the fine-grained analysis, we stratified the sample into age,
BMI, and smoking subgroups and tested for mean differences in the intermediate
traits between children with and without a strong family history. For seven of
the nine intermediate traits we found evidence of significant mean differences
between children with and without a strong family history of CAD in particular
age and BMI subgroups in nonsmokers that were not expected given the results from
separate age-dependent or BMI-dependent marginal analyses. From these analyses,
we conclude that the inferences about intermediate biochemical and physiological
trait associations with family history of CAD depend on where on the coarse-grain
to fine-grain continuum of context dependency the analysis is performed. In many
cases, inferences at one level of investigation are different than the inferences
made at a coarser or finer level. This study documents the complexity of the
associations between intermediate traits and risk of CAD and raises the question
of how many models are needed to maximize disease prediction and where these
models should fall on the coarse- to fine-grain continuum.
PMID- 9635997
TI - Coffee consumption in hypertensive men in older middle-age and the risk of
stroke: the Honolulu Heart Program.
AB - OBJECTIVE: To examine the association between coffee consumption and the
development of stroke in men at high risk for cardiovascular disease. METHODS:
Coffee intake was observed from 1965 to 1968 in a cohort of men enrolled in the
Honolulu Heart Program with follow-up for incident stroke over a 25-year period.
Subjects were 499 hypertensive men (having systolic or diastolic blood pressures
at or above 140 and 90 mm Hg, respectively) in older middle-age (55 to 68 years)
when follow-up began. Past and current cigarette smokers were excluded from
follow-up. RESULTS: In the course of follow-up, 76 men developed a stroke. After
age-adjustment, risk of thromboembolic stroke increased significantly with
increases in coffee consumption (P = 0.002). No relationships were observed with
hemorrhagic stroke. When adjusted for other factors, the risk of thromboembolic
stroke was more than doubled for men who consumed three cups of coffee per day as
compared to nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7). CONCLUSIONS:
Although in need of further confirmation, consumption of coffee appears to be
positively associated with an increased risk of thromboembolic stroke in
hypertensive men in older middle-age. Findings suggest that it may be prudent to
advise older middle-aged men with hypertension who consume large amounts of
coffee to consider reducing their coffee intake.
PMID- 9635998
TI - Prevalence and risk factors for nosocomial lower respiratory tract infections in
German hospitals.
AB - The prevalence and risk factors for nosocomial lower respiratory tract infections
(LRTI) in Germany were determined as part of a national survey on nosocomial
infections. The study included 14,966 patients in 72 representatively selected
hospitals with departments of general medicine, surgery, obstetrics, gynecology,
and intensive care units (ICU). Surveillance was carried out by four previously
validated medical doctors who strictly applied the CDC-criteria for diagnosis of
nosocomial infections. The overall prevalence of hospital-acquired LRTI was 0.72%
with the highest rate in hospitals with more than 600 beds (1.08%) and among the
patients on intensive care units (9.00%). Ventilator-associated pneumonia rates
were highest in patients on ICUs (13.27). Polytrauma, impaired consciousness,
chronic airway disease, prior surgery, and cardiovascular disease were
significantly related to the occurrence of nosocomial LRTI. P. aeruginosa was the
predominant organism causing nosocomial LRTI. Nosocomial LRTI remain a problem
mainly on ICUs. Patients at risk should be monitored with extra care.
PMID- 9635999
TI - Comparative safety of two recombinant hepatitis B vaccines in children: data from
the Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink
(VSD).
AB - BACKGROUND: Preliminary review of data from the Vaccine Adverse Event Reporting
System (VAERS), 1991-1994, revealed that more serious adverse events were
reported in children who received a specific brand of recombinant hepatitis B
(HepB) vaccine. OBJECTIVE: To compare the post-marketing safety experience of the
two recombinant HepB vaccines licensed for use in infants and children in the
United States. DESIGN: Review of a case series derived from passive surveillance
data in the national VAERS. A retrospective cohort study using data from one
health maintenance organization participating in Vaccine Safety Datalink (VSD), a
computerized record linkage system. POPULATIONS STUDIED: U.S. children, ages
birth-10 years for whom adverse events after HepB vaccine were reported to VAERS,
1991-1994. Children, ages birth-6 years, who received HepB vaccine at Kaiser
Permanente Medical Care Program, Northern California, 1991-1994. MAIN OUTCOME
MEASURES: VAERS reporting rates for each vaccine by manufacturer were calculated
from the numbers of reported events occurring within 30 days of HepB vaccination
and the number of doses distributed by the manufacturers. VSD event rates for
each vaccine were calculated from the numbers of hospitalization or emergency
room visits within 30 days of HepB vaccination and the number of vaccine doses
administered to the cohort. RESULTS: In VAERS, higher rates of serious events
(i.e., life threatening or resulting in hospitalization or permanent disability)
were reported in children who received Vaccine A vs. Vaccine B (relative risk
[RR]: 3.13-8.18, P < 0.01), particularly by those vaccinated in the private (RR:
7.62-28.58, P < 0.01), but not public sector (RR: 2.12, P = 0.19). Similar types
of events were reported in recipients of both vaccines. In contrast, analysis of
VSD data showed no significant difference in rates of hospitalization or ER
visits in children who received either HepB vaccine (RR: 0.96-1.25, P > 0.05).
CONCLUSIONS: Our investigation reveals that it is unlikely there is a true
difference between rates of serious events temporally associated with the two
HepB vaccines in children. This study demonstrates the dual roles played by VAERS
and VSD in providing a more complete picture of the post-marketing safety profile
of childhood vaccines, and underscores the importance of using other analytic
studies to evaluate findings from passive surveillance systems of adverse events.
PMID- 9636000
TI - A case-control study on risk factors for Peyronie's disease.
AB - The aim of this study was to investigate the relationship between history of
selected diseases, genital traumas, and Peyronie's disease. A hospital-based case
control study was conducted at the Andrologic and Surgical Outpatient Units of
the Policlinico Gemelli, Rome, where 134 men with Peyronie's disease and 134 male
controls were interviewed. The association between Peyronie's disease and
selected characteristics was estimated by means of odds ratios (OR) and 95%
confidence intervals (CI). Patients who underwent invasive procedures on the
penis (i.e., urethral catheterization, cystoscopy, and transurethral
prostatectomy) had a 16-fold increased risk for Peyronie's disease (OR = 16.1,
95% CI: 1.8-142), while a nearly three-fold increase was observed among patients
who had genital and/or perineal traumatisms (95% CI: 1.0-7.1). A history of
urethritis, uricacidemia, and lipoma was also significantly associated with an
increased risk for Peyronie's disease. Twenty-one percent of the cases and none
of the controls were affected by Dupuytren's contracture, and 4% of cases and
none of the controls reported familial history for Peyronie's disease. The
frequency of inflammatory or fibromatous lesions of the genital tract of the
partner was significantly higher in men with Peyronie's disease than among
controls. These results were consistent when performing a stratified analysis
according to the type of controls (i.e., controls affected by urologic or by
digestive conditions) to rule out the potential effect of recall bias. The
findings of the study lend support to clinical reports stressing the importance
of genital traumatisms and genetic conditions in the development of Peyronie's
disease.
PMID- 9636001
TI - Validation of a telephone questionnaire for Parkinson's disease.
AB - As part of a genetic study, we investigated the accuracy of a telephone
questionnaire to diagnose or screen for Parkinson's disease (PD). We studied 20
PD patients randomly selected among all incident cases in Olmsted County,
Minnesota, for the period 1970 through 1988. Each patient was matched by age and
sex to a subject free of PD or parkinsonism residing in the same county. In
addition, we studied 20 patients with PD referred to our institution from outside
of Olmsted County between 1991 and 1993. Medical record documentation of disease
status for both affected and unaffected subjects served as the standard for
comparison. A trained interviewer kept unaware of disease status administered
nine symptom questions via telephone to all study subjects (or their proxy).
Seventeen PD cases from Olmsted County, all 20 referral cases, and 16 unaffected
subjects participated in the interview (total = 37 with PD and 16 unaffected
subjects); 36 interviews (24 PD) were with a proxy and 17 (13 PD) were direct.
Questions regarding "poor balance," "trouble buttoning," and "trouble arising"
had the highest sensitivity; questions regarding "shaking," "feet stuck to the
floor," "softer voice," and "smaller writing" had the highest specificity. A
combination of any four symptoms yielded the best balance between sensitivity
(89%) and specificity (88%). Although the questionnaire appears to be useful both
as a screening and as a diagnostic tool, it failed to reach complete accuracy,
and it should be used in the context of a more complex case-finding strategy.
PMID- 9636002
TI - Instructions for editors: a "revenge fantasy".
PMID- 9636003
TI - Zeta and delta: critical descriptive boundaries in statistical analysis.
PMID- 9636004
TI - Is HDR brachytherapy for carcinoma of the uterine cervix high-throughput but high
risk?
PMID- 9636005
TI - High and low dose-rate brachytherapy for cervical carcinoma.
AB - For the brachytherapy component of the radiation treatment of cervical carcinoma,
high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due
primarily to radiation safety and other physical benefits attributed to the HDR
modality. Many radiation oncologists are reluctant to make this change because of
perceived radiobiological disadvantages of HDR. However, in clinical practice HDR
appears to be as effective as LDR but with a lower risk of late complications, as
demonstrated by one randomized clinical trial and two comprehensive literature
and practice surveys. The reason for this appears to be that the radiobiological
disadvantages of HDR are outweighed by the physical advantages.
PMID- 9636006
TI - Radiation-induced changes in a cell's program for life.
PMID- 9636007
TI - Programmed cellular response to ionizing radiation damage.
AB - Three forms of radiation response were investigated to evaluate the hypothesis
that cellular radiation response is the result of active molecular signaling and
not simply a passive physicochemical process. The decision whether or not a cell
should respond to radiation-induced damage either by induction of rescue systems,
e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g.
programmed cell death, appears to be the expression of intricate cellular
biochemistry. A cell must recognize damage in its genetic material and then
activate the appropriate responses. Cell type is important; the response of a
fibroblast to radiation damage is both quantitatively and qualitatively different
from that of a lymphocyte. The programmed component of radiation response is
significant in radiation oncology and predicted to create unique opportunities
for enhanced treatment success.
PMID- 9636009
TI - Fractionation effect on radiation-induced growth retardation of tibia in rabbits
and rats.
AB - A study of the sensitivity to fractionation of the growing tibia of rabbits and
rats was conducted by comparing the growth of the treated right bone to that of
the untreated left side in each individual animal using radiographic
measurements. The experimental endpoint was the percentage of normal growth 24
weeks after irradiation in rabbits and 14 weeks after treatment in rats. The
results show clear dose-response relationships in all experimental arms. A clear
cut fractionation effect was demonstrated in both species. The alpha/beta-ratios
determined by maximum likelihood analysis according to the LQ-model with graded
responses were 3.2 Gy (95% C.I. 1.1; 5.6) in rabbits and 6.9 Gy (5.3; 8.7) in
rats, when all data were included in the calculations. When single-dose data were
excluded the alpha/beta-values were -0.6 Gy (-3.1; 2.3) in rabbits and 5.0 Gy
(3.5; 7.0) in rats. Our data provide further evidence that low doses per fraction
should be used when irradiation of the epiphysis cannot be avoided in pediatric
patients.
PMID- 9636008
TI - Radiotherapy combined with transcatheter arterial infusion chemotherapy for
locally advanced cervical cancer.
AB - Twenty-four patients with locally advanced cervical cancer were treated with
radiation therapy (RT) and transcatheter arterial infusion (TAI) chemotherapy,
while 22 patients were treated with RT alone. RT consisted of a combination of
external irradiation and high-dose-rate intracavitary brachytherapy. TAI therapy
consisted of two sessions using cisplatin and pirarubicin, performed concurrently
during the periods of external irradiation. The local-regional control rates at 1
year for the patients treated with RT plus TAI and for those treated with RT
alone were 87.5% and 58.3%, respectively (p < 0.05). The 3-year cause-specific
survival (CSS) rates for RT plus TAI, and RT alone were 67.1% and 55.9%,
respectively (p = n.s.). The 3-year CSS rate for the 14 patients treated with RT
and TAI who had well- or moderately differentiated squamous cell carcinoma
without pelvic lymph node swelling was 100%, while that for the 19 patients with
the same background treated with RT alone was 49% (p < 0.01). Radiation therapy
combined with TAI appears to be an effective and safe treatment modality for
patients with locally advanced cervical cancer.
PMID- 9636010
TI - A quality assurance network in Central European countries--radiotherapy
infrastructure.
AB - A survey of the infrastructure in radiotherapy centres in three Central European
countries has been performed as a first step in the development of a quality
assurance network. Data concerning radiotherapy equipment, staff and number of
patients treated in most of the radiotherapy centres from Czech Republic, Poland
and Hungary were collected at the beginning of 1994. Equipment data have shown
that 35% of 182 treatment units are conventional x-ray units, 35% 60Co units, 19%
linear accelerators, 7% 137Cs units and 4% betatrons. About 47% of high energy
units are older than 12 years and about 20% older than 21 years. An important
number of centres still have no simulator which would constitute an important
handicap to carry out adequate radiotherapy. The number of treatment planning
systems has also been registered; 44% being PC-based systems with locally
developed software. Large variations are observed in the number of patients
treated per year, per high energy unit, but 12/47 centres treat more than 700
patients per year and unit. On the average, staffing seems adequate in numbers
though there are wide variations. The main limitation of radiotherapy
infrastructure in the Central European countries is the low number of linear
accelerators and simulators and the advanced age of therapy units.
PMID- 9636011
TI - Recurrence after different primary treatment for cancer of the supraglottic
larynx.
AB - Retrospective analysis of patient records at two hospitals was performed with the
principal goal of clarifying the role of primary radiotherapy ill patients with
squamous cell carcinoma of the supraglottic larynx. Primary surgery was
frequently performed during the first period from 1958 to 1978. Primary
radiotherapy with surgery in reserve was the prevailing therapy during the second
period from 1978 to 1993. Fewer recurrences were observed during the second
period. The improved results were apparent mainly in patients with the more
advanced stages (III, T4N0 and T4N1). Analysis of many factors suggest that the
more frequent choice of primary radiotherapy with surgery in reserve, or applied
as preoperative treatment, with optimal dosage and technique, might have
contributed to the improved results.
PMID- 9636012
TI - Avascular necrosis of bone--a complication of aggressive therapy for acute
lymphoblastic leukemia.
AB - The purpose of the present paper was to report cases of avascular necrosis of
bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic
leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on
patients with symptoms of bone pain, whereby five patients out of 850 patients
were detected to have avascular necrosis of the femoral head. All had received
aggressive chemotherapy with steroids. Two patients were still on therapy for the
primary disease. In these patients further chemotherapy was continued without
steroids. The median period from diagnosis of ALL to development of AVNB was 29
months. Three patients underwent corrective surgical procedures. To conclude, the
data suggest that patients receiving combination chemotherapy, especially those
with high cumulative doses, run a risk of developing AVNB. Awareness of this
complication is important in order to have an early diagnosis so as to limit
disability.
PMID- 9636013
TI - Growth hormone reduces mortality and bacterial translocation in irradiated rats.
AB - Growth hormone stimulates the growth of intestinal mucosa and may reduce the
severity of injury caused by radiation. Male Wistar rats underwent abdominal
irradiation (12 Gy) and were treated with either human growth hormone (hGH) or
saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation,
and the ileal mucosal thickness, proliferation, and disaccharidase activity were
assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement
(29%, p < 0.05). Bacterial translocation was also reduced by hGH (p < 0.05).
Treating irradiated rats with hGH prevented body weight loss (p < 0.05). Mucosal
thickness increased faster in irradiated hGH-treated animals. The proliferative
index showed an increment in hGH-treated animals (p < 0.05). Giving hGH to
irradiated rats prevented decrease in sucrose activity, and increment in lactase
activity. In conclusion, giving hGH to irradiated rats promotes the adaptative
process of the intestine and acute radiation-related negative effects, including
mortality, bacterial translocation, and weight loss.
PMID- 9636014
TI - Phase II study of estramustine and vinorelbine in hormone-refractory prostate
carcinoma patients.
AB - The purpose of this study was to evaluate the antitumor activity of vinorelbine
and oral estramustine phosphate in patients with metastatic, hormone-refractory
prostate cancer. We evaluated the activity of this association using the
following schedule: estramustine phosphate 600 mg/m2/day orally days 1-42 and
vinorelbine 25 mg/m1 days 1, 8, 22, 29 cycles repeated every 56 days. Twenty-five
patients were included in the study, 24 being evaluable for response and 25 for
toxicity. Out of 5 patients with measurable disease, none had an objective
response. Of the 24 assessable patients with bone metastases, 9 patients had a >
or = 65% decline in pretreatment prostate-specific antigen (PSA) level, stable
disease was observed in 10 and 5 patients progressed. Toxicities were minimal.
Anemia was observed in 5 patients, alopecia in 4 and nausea and vomiting was
observed in 6 patients. Anorexia and weight loss of more than 10% were observed
in 2 patients. This combination is active and well tolerated in hormone-resistant
prostate cancer. These results support the therapeutic strategy of combining
agents that impair microtubule function.
PMID- 9636015
TI - Alterations of the immunoglobulin heavy chain locus in progressive B-cell
lymphomas.
AB - Twenty-two patients with relapsed or progressive B-cell lymphomas (BCL) were
analysed for alterations in the rearrangement status in the immunoglobulin heavy
(IgH) chain gene in samples obtained on different occasions during the course of
the disease. The analysis was performed using Southern blot hybridization of the
IgH gene and polymerase chain reaction (PCR) amplification of the VH gene
families combined with single-strand conformation polymorphism (SSCP) analysis.
Using Southern blot analysis, we found that all 22 lymphomas displayed clonal IgH
rearrangements, and changes during tumour progression occurred in 8 cases. These
alterations were mainly observed in cases with follicular or transformed
lymphomas. More than one malignant (sub)clone, indicated by more than two
rearranged bands, was detected in one case at diagnosis and in three cases at
relapse. Outgrowth of subclones with divergent rearrangement patterns in
different compartments was also observed in 2 out of 8 cases. PCR-SSCP analysis
indicated that all 15 cases studied displayed clonal rearrangements and in 6
cases altered rearrangement patterns were detected in later samples. Southern
blotting and PCR-SCCP analysis gave equivalent results. No association was found
between time to relapse or survival time and alterations in rearrangement
pattern. The present study illustrates that the neoplastic cell clones in BCL
often display alterations in their IgH locus, but the significance of this
feature remains to be clarified.
PMID- 9636016
TI - Radiation-induced insufficiency fractures after definitive prostate cancer
radiotherapy.
PMID- 9636017
TI - Discordant washout of 99mTc sestamibi and 99mTc tetrofosmin in a patient with
mediastinal seminoma.
PMID- 9636018
TI - Multiple smooth-muscle neoplasm and thyroid carcinoma in an adult with AIDS.
PMID- 9636019
TI - Breast angiosarcoma after conservative surgery, radiotherapy and prosthesis
implant.
PMID- 9636020
TI - Leiomyosarcoma of the gallbladder--a case report and review of the literature.
PMID- 9636021
TI - Solution structure of the transmembrane H+-transporting subunit c of the F1F0 ATP
synthase.
AB - Subunit c is the H+-translocating component of the F1F0 ATP synthase complex. H+
transport is coupled to conformational changes that ultimately lead to ATP
synthesis by the enzyme. The properties of the monomeric subunit in a single
phase solution of chloroform-methanol-water (4:4:1) have been shown to mimic
those of the protein in the native complex. Triple resonance NMR experiments were
used to determine the complete structure of monomeric subunit c in this solvent
mixture. The structure of the protein was defined by >2000 interproton distances,
64 (3)JN alpha, and 43 hydrogen-bonding NMR-derived restraints. The root mean
squared deviation for the backbone atoms of the two transmembrane helices was
0.63 A. The protein folds as a hairpin of two antiparallel helical segments,
connected by a short structured loop. The conserved Arg41-Gln42-Pro43 form the
top of this loop. The essential H+-transporting Asp61 residue is located at a
slight break in the middle of the C-terminal helix, just prior to Pro64. The C
terminal helix changes direction by 30 +/- 5 degrees at the conserved Pro64. In
its protonated form, the Asp61 lies in a cavity created by the absence of side
chains at Gly23 and Gly27 in the N-terminal helix. The shape and charge
distribution of the molecular surface of the monomeric protein suggest a packing
arrangement for the oligomeric protein in the F0 complex, with the front face of
one monomer packing favorably against the back face of a second monomer. The
packing suggests that the proton (cation) binding site lies between packed pairs
of adjacent subunit c.
PMID- 9636022
TI - Carbamoyl phosphate synthetase: caught in the act of glutamine hydrolysis.
AB - Carbamoyl phosphate synthetase from Escherichia coli catalyzes the production of
carbamoyl phosphate from two molecules of Mg2+ATP, one molecule of bicarbonate,
and one molecule of glutamine. The enzyme consists of two polypeptide chains
referred to as the large and small subunits. While the large subunit provides the
active sites responsible for the binding of nucleotides and other effector
ligands, the small subunit contains those amino acid residues that catalyze the
hydrolysis of glutamine to glutamate and ammonia. From both amino acid sequence
analyses and structural studies it is now known that the small subunit belongs to
the class I amidotransferase family of enzymes. Numerous biochemical studies have
suggested that the reaction mechanism of the small subunit proceeds through the
formation of the glutamyl thioester intermediate and that both Cys 269 and His
353 are critical for catalysis. Here we describe the X-ray crystallographic
structure of carbamoyl phosphate synthetase from E. coli in which His 353 has
been replaced with an asparagine residue. Crystals employed in the investigation
were grown in the presence of glutamine, and the model has been refined to a
crystallographic R-factor of 19.1% for all measured X-ray data from 30 to 1.8 A
resolution. The active site of the small subunit clearly contains a covalently
bound thioester intermediate at Cys 269, and indeed, this investigation provides
the first direct structural observation of an enzyme intermediate in the
amidotransferase family.
PMID- 9636023
TI - Autocatalytic formation of a hydroxy group at C beta of trp171 in lignin
peroxidase.
AB - In the high-resolution crystal structures of two lignin peroxidase isozymes from
the white rot fungus Phanerochaete chrysosporium a significant electron density
at single bond distance from the C beta of Trp171 was observed and interpreted as
a hydroxy group. To further clarify the nature of this feature, we carried out
tryptic digestion of the enzyme and isolated the Trp171 containing peptide. Under
ambient conditions, this peptide shows an absorbance spectrum typical of
tryptophan. At elevated temperature, however, the formation of an unusual
absorbance spectrum with lambda max = 333 nm can be followed that is identical to
that of N-acetyl-alpha, beta-didehydrotryptophanamide, resulting upon water
elimination from beta-hydroxy tryptophan. The Trp171 containing tryptic peptide
isolated from the recombinant and refolded lignin peroxidase produced from
Escherichia coli does not contain the characteristic 333 nm absorbance band at
any temperature. However, treatment with 3 equiv of H2O2 leads to complete
hydroxylation of Trp171. Reducing substrates compete with this process, e.g., in
the presence of 0.5 mM veratryl alcohol, about 7 equiv of H2O2 is necessary for
complete modification. We conclude that the hydroxylation at the C beta of Trp171
is an autocatalytic reaction which occurs readily under conditions of natural
turnover, e.g., in the ligninolytic cultures of P. chrysosporium, which are known
to contain an oxidase-based H2O2-generating system. No dependence on dioxygen was
found for this oxidative process. Chemical modification of fungal lignin
peroxidase with the tryptophan-specific agent N-bromo succinimide leads to a
drastically reduced activity with respect to the substrate veratryl alcohol. This
suggests that Trp171 is involved in catalysis and that electron transfer from
this surface residue to the oxidized heme cofactor is possible under steady-state
conditions.
PMID- 9636024
TI - Site-directed mutagenesis of the conserved threonine (Thr243) of the distal helix
of fungal cytochrome P450nor.
AB - Cytochrome P450nor (P450nor) is a heme enzyme which catalyzes NO reduction in
denitrifying fungi. Threonine 243 (Thr243) of P450nor, which corresponds to the
conserved threonine of monooxygenase cytochrome P450s, was replaced by 18
different amino acids via site-directed mutagenesis. The mutation did not
seriously affect the optical absorption and the CD spectral properties of the
enzyme in several oxidation, ligation, or spin states or the association rate
constant for association of NO with the ferric iron, suggesting subtle and local
structural changes in the heme environment on Thr243 mutation. However, the NO
reduction activity was dramatically altered by Thr243 mutation, depending on the
properties of the replaced amino acids. The catalytic activity, as measured by
N2O formation and NADH consumption, was considerably retained on substitution of
Asn, Ser, and Gly for Thr243, while it was profoundly decreased or lost on
substitution with other amino acids. Kinetic analysis of the reaction of the
enzymes with NO and NADH indicated that the decrease in the enzymatic activity
upon Thr243 mutation mainly results from a decrease in the rate of reduction of
the ferric-NO complex with NADH. On the basis of these enzymatic, kinetic, and
spectroscopic results, as well as on the basis of the crystal data for native
P450nor [Park, S.-Y., et al. (1997) Nat. Struct. Biol. 4, 827-832], the role of
the conserved threonine at the 243 position in the NO reduction reaction by
P450nor is discussed. We also discuss structural similarities or differences in
the vicinity of the conserved threonine between P450nor and other monooxygenase
P450s.
PMID- 9636025
TI - Design of a novel P450: a functional bacterial-human cytochrome P450 chimera.
AB - We report the construction of a functional chimera from approximately 50%
bacterial (cytosolic) cytochrome P450cam and 50% mammalian (membrane-bound)
cytochrome P450 2C9. The chimeric protein shows a reduced CO-difference spectrum
absorption at 446 nm, and circular dichroism spectra indicate that the protein is
globular. The protein is soluble and catalyzes the oxidation of 4-chlorotoluene
using molecular oxygen and reducing equivalents from bacterial putidaredoxin and
putidaredoxin reductase. This chimera provides a novel method for addressing
structure-function issues and may prove useful in the design of oxidants for
benign and stereospecific synthesis, as well as catalysts for bioremediation of
polluted areas. Furthermore, these results provide the first evidence that
bacterial P450 enzymes and mammalian P450 enzymes are likely to share a common
tertiary structure.
PMID- 9636026
TI - Colocalization of heparin and receptor binding sites on keratinocyte growth
factor.
AB - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor
(FGF) family. FGFs are also known as heparin-binding growth factors because they
bind to heparin and their physical and biological properties are modulated by
heparin. Consistent with a role as a paracrine effector, KGF is produced by cells
of mesenchymal origin but is active primarily, if not exclusively, on epithelial
cells. KGF is involved in a variety of physiological processes, including
proliferation, differentiation, wound healing, and cytoprotection. To identify
regions in KGF that contribute to heparin and tyrosine kinase receptor
interactions, nine peptides spanning defined motifs in the predicted structure of
KGF were synthesized, and their heparin and receptor binding properties were
analyzed. Peptides at the amino and carboxyl termini bound heparin, and one
peptide showed relative binding comparable to that of KGF. Competitive binding
studies showed that this peptide along with two other overlapping peptides
specifically displaced KGF bound to the KGF receptor. These three peptides were
also selectively recognized by a neutralizing monoclonal antibody against KGF,
though only in the presence of heparin. Together, these data suggest that the
sites for heparin and receptor binding both reside in the amino and carboxyl
termini of KGF, which are spatially juxtaposed in the predicted three-dimensional
structure of this molecule.
PMID- 9636027
TI - Thermodynamics of the interaction of human immunoglobulin E with its high
affinity receptor Fc epsilon RI.
AB - We have employed isothermal titration calorimetry (ITC) and circular dichroism
(CD) spectroscopy to characterize the binding of soluble fragments of IgE (IgE-Fc
and Fc epsilon 3-4) to a soluble fragment of the high-affinity receptor Fc
epsilon RI alpha-chain (sFc epsilon RI alpha). The thermodynamic parameters for
the interaction of IgE-Fc and Fc epsilon 3-4 with sFc epsilon RI alpha,
determined using ITC, confirm the earlier conclusion that the C epsilon 2 domain
is not involved in the interaction and that the stoichiometry of both complexes
is 1:1. For both IgE-Fc and Fc epsilon 3-4, the value of Delta H degrees is -36.9
+/- 4.6 kcal mol-1 at 37.3 degreesC and Delta Cp degrees is -820 +/- 120 cal mol
1 K-1. The temperature at which DeltaS degrees is zero is 284 +/- 1 K, indicating
that the entropy contribution to the thermodynamics of association is unfavorable
at physiological temperature. Of particular interest is the large value of Delta
Cp degrees. The large surface area of IgE and Fc epsilon RI alpha that is
implicated in complex formation from previous mutagenesis studies on the two
proteins may account in part for the magnitude of Delta Cp degrees. Additional
contributions may arise from hydration within the binding site and changes in
tertiary structure of the individual components of the complex. However, the CD
spectra of IgE, IgE-Fc, and Fc epsilon 3-4 complexes with sFc epsilon RI alpha
are merely the sum of the spectra of their individual components, indicating that
the secondary structure of the immunoglobulin domain folds are preserved on
complex formation. Thus, any change in tertiary structure must be limited to the
relative disposition of the immunoglobulin domains C epsilon 3 and C epsilon 4 in
IgE and the two immunoglobulin-like domains in the alpha-chain of Fc epsilon RI.
PMID- 9636028
TI - Molecular mimics of insulin-like growth factor 1 (IGF-1) for inhibiting IGF-1:
IGF-binding protein interactions.
AB - IGF-1 (insulin-like growth factor 1) is a 70-residue protein hormone which has
both metabolic and mitogenic activities mediated through IGF-1 binding to cell
surface receptors. However, an unrelated class of proteins, the IGF-binding
proteins (IGFBPs) also bind IGF-1 in the serum and tissues and block or modulate
its activity in vivo. Therefore, inhibitors of the IGFBPs can alter the
distribution between free and bound IGF-1 [Loddick, S. A., Liu, X.-J., Lu, Z.-X.,
Liu, C., Behan, D. P., Chalmers, D. C., Foster, A. C., Vale, W. W., Ling, N., and
De Souza, E. B. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 1894-1898] and
potentially affect the distribution of IGF-1 among body tissues. We report here
that phage-displayed peptide libraries have yielded a peptide that binds IGFBP-1
and produces IGF-like activity at sub-micromolar concentrations. The 14-residue
peptide has an extremely well-defined solution conformation that can aid in the
design of smaller, orally active compounds. Interestingly, the peptide structure
contains a helix, as does one region of IGF-1 previously implicated in IGFBP
binding, yet displays side chains different from those of the IGF-1 helix I.
Furthermore, an IGF-1 variant lacking receptor-signaling activity in vitro is
shown here to produce IGF-like mitogenic and metabolic activity in vivo. These
results suggest that small antagonist mimetics of protein ligands, identified by
binding selection to otherwise inhibitory factors, may be useful as indirect
agonists for a variety of therapeutic applications.
PMID- 9636029
TI - Competitive inhibition of MAP kinase activation by a peptide representing the
alpha C helix of ERK.
AB - On the basis of the crystal structure of the MEK substrate ERK, we have
synthesized a 15 amino acid peptide representing the alpha C helix of human ERK1.
We find this peptide to be an inhibitor of ERK phosphorylation by its upstream
activator MEK. Circular dichroic spectroscopy indicates that the peptide has
little secondary structure in aqueous buffer, but can readily adopt an alpha
helical structure in aprotic solvent. Steady-state kinetic analysis indicates
that the peptide serves as a competitive inhibitor of ERK binding to MEK, with a
dissociation constant, Ki, of 0.84 microM. Together with ATP-competitive
inhibitors of MEK, we have used this peptide to define the kinetic mechanism of
MEK catalysis. These studies reveal that MEK operates through a bi-bi random
ordered sequential mechanism. The synthetic peptide inhibits also the
phosphorylation of p38 and ERK by the upstream activator MKK3, but is at least 3
fold less potent as an inhibitor of SEK activation of JNK1. Interestingly, the
peptide also showed some ability to inhibit ERK-mediated phosphorylation of
myelin basic protein, but was inactive as an inhibitor of the unrelated kinases
Raf, Abl, and PKA. These results imply that the alpha C helix is an important
locus of interaction for the formation of a MEK-ERK complex. The alpha C helix
cannot, however, be the sole determinant of activator selectivity among the MAP
kinases. Molecules designed to target the alpha C helix binding pocket of MAP
kinase activators may provide a novel means of inhibiting these signal
transducers.
PMID- 9636031
TI - Product inhibition of the hepatitis C virus NS3 protease.
AB - The nonstructural protein NS3 of the hepatitis C virus (HCV) harbors a serine
protease domain that is responsible for most of the processing events of the
nonstructural region of the polyprotein. Its inhibition is presently regarded as
a promising strategy for coping with the disease caused by HCV. In this work, we
show that the NS3 protease undergoes inhibition by the N-terminal cleavage
products of substrate peptides corresponding to the NS4A-NS4B, NS4B-NS5A, and
NS5A-NS5B cleavage sites, whereas no inhibition is observed with a cleavage
product of the intramolecular NS3-NS4A junction. The Ki values of the hexamer
inhibitory products [Ki(NS4A) = 0.6 microM, Ki(NS5A) = 1.4 microM, and Ki(NS4B) =
180 microM] are lower than the Km values of the respective substrate peptides
[Km(NS4A-NS4B) = 10 microM, Km(NS5A-NS5B) = 3.8 microM, and Km(NS4B-NS5A) > 1000
microM]. Mutagenesis experiments have identified Lys136 as an important
determinant for product binding. The phenomenon of product inhibition can be
exploited to optimize peptide inhibitors of NS3 protease activity that may be
useful in drug development.
PMID- 9636030
TI - His...Asp catalytic dyad of ribonuclease A: structure and function of the wild
type, D121N, and D121A enzymes.
AB - The side chains of histidine and aspartate residues form a hydrogen bond in the
active sites of many enzymes. In serine proteases, the His...Asp hydrogen bond of
the catalytic triad is known to contribute greatly to catalysis, perhaps via the
formation of a low-barrier hydrogen bond. In bovine pancreatic ribonuclease A
(RNase A), the His...Asp dyad is composed of His119 and Asp121. Previously, site
directed mutagenesis was used to show that His119 has a fundamental role, to act
as an acid during catalysis of RNA cleavage [Thompson, J. E., and Raines, R. T.
(1994) J. Am. Chem. Soc. 116, 5467-5468]. Here, Asp121 was replaced with an
asparagine or alanine residue. The crystalline structures of the two variants
were determined by X-ray diffraction analysis to a resolution of 1.6 A with an R
factor of 0.18. Replacing Asp121 with an asparagine or alanine residue does not
perturb the overall conformation of the enzyme. In the structure of D121N RNase
A, Ndelta rather than Odelta of Asn121 faces His119. This alignment in the
crystalline state is unlikely to exist in solution because catalysis by the D121N
variant is not compromised severely. The steady-state kinetic parameters for
catalysis by the wild-type and variant enzymes were determined for the cleavage
of uridylyl(3'-->5')adenosine and poly(cytidylic acid), and for the hydrolysis of
uridine 2',3'-cyclic phosphate. Replacing Asp121 decreases the values of kcat/Km
and kcat for cleavage by 10-fold (D121N) and 10(2)-fold (D121A). Replacing Asp121
also decreases the values of kcat/Km and kcat for hydrolysis by 10(0. 5)-fold
(D121N) and 10-fold (D121A) but has no other effect on the pH-rate profiles for
hydrolysis. There is no evidence for the formation of a low-barrier hydrogen bond
between His119 and either an aspartate or an asparagine residue at position 121.
Apparently, the major role of Asp121 is to orient the proper tautomer of His119
for catalysis. Thus, the mere presence of a His...Asp dyad in an enzymic active
site is not a mandate for its being crucial in effecting catalysis.
PMID- 9636032
TI - Potent peptide inhibitors of human hepatitis C virus NS3 protease are obtained by
optimizing the cleavage products.
AB - In the absence of a broadly effective cure for hepatitis caused by hepatitis C
virus (HCV), much effort is currently devoted to the search for inhibitors of the
virally encoded protease NS3. This chymotrypsin-like serine protease is required
for the maturation of the viral polyprotein, cleaving it at the NS3-NS4A, NS4A
NS4B, NS4B-NS5A, and NS5A-NS5B sites. In the course of our studies on the
substrate specificity of NS3, we found that the products of cleavage
corresponding to the P6-P1 region of the substrates act as competitive inhibitors
of the enzyme, with IC50s ranging from 360 to 1 microM. A detailed study of
product inhibition by the natural NS3 substrates is described in the preceding
paper [Steinkuhler, C., et al. (1997) Biochemistry 37, 8899-8905]. Here we report
the results of a study of the structure-activity relationship of the NS3 product
inhibitors, which suggest that the mode of binding of the P region-derived
products is similar to the ground-state binding of the corresponding substrates,
with additional binding energy provided by the C-terminal carboxylate. Optimal
binding requires a dual anchor: an "acid anchor" at the N terminus and a "P1
anchor" at the C-terminal part of the molecule. We have then optimized the
sequence of the product inhibitors by using single mutations and combinatorial
peptide libraries based on the most potent natural product, Ac-Asp-Glu-Met-Glu
Glu-Cys-OH (Ki = 0.6 microM), derived from cleavage at the NS4A-NS4B junction. By
sequentially optimizing positions P2, P4, P3, and P5, we obtained several
nanomolar inhibitors of the enzyme. These compounds are useful both as a starting
point for the development of peptidomimetic drugs and as structural probes for
investigating the substrate binding site of NS3 by modeling, NMR, and
crystallography.
PMID- 9636033
TI - Hydrophobic core substitutions in calbindin D9k: effects on stability and
structure.
AB - The effects of hydrophobic core mutations on the stability and structure of the
four-helix calcium-binding protein, calbindin D9k, have been investigated. Eleven
mutations involving eight residues distributed within the hydrophobic core of
calbindin D9k were examined. Stabilities were measured by denaturant and thermal
induced unfolding monitored by circular dichroism spectroscopy. The mutations
were found to exert large effects on the stability with midpoints in the urea
induced unfolding varying from 1.8 M for Leu23 --> Gly up to 6.6 M for Val70 -->
Leu and free energies of unfolding in the absence of denaturant ranging from 6.6
to 27.4 kJ/mol for the Phe66 --> Ala mutant and the wild-type, respectively. A
significant correlation was found between the difference in free energy of
unfolding (Delta Delta GNU) and the change in the surface area of the side chain
caused by the mutation, in agreement with other studies. Notably, both increases
and decreases in side-chain surface area caused quantitatively equivalent effects
on the stability. In other words, a correlation between the absolute value of the
change in the surface of the side chain and Delta DeltaGNU was observed with a
value of approximately 0.14 kJ M-1 A-2. The generality of this observation is
discussed. Significant effects on the cooperativity of the unfolding reaction
were also observed. However, a correlation between the cooperativity and Delta
Delta GNU, which has been reported in other systems as an indication of effects
of mutations on the unfolded state, was not observed for calbindin D9k. Despite
the large effects on Delta Delta GNU and cooperativity, the structures of the
mutants in the native form remained intact as indicated by circular dichroism,
NMR, and fluorescence measurements. The structural response to calcium-binding
was also conserved. The following paper in this issue [Kragelund, B. B., et al.
(1998) Biochemistry 37, 8926-8937] examines the effects of these mutations on the
calcium binding properties of calbindin D9k.
PMID- 9636034
TI - Hydrophobic core substitutions in calbindin D9k: effects on Ca2+ binding and
dissociation.
AB - Hydrophobic core residues have a marked influence on the Ca2+-binding properties
of calbindin D9k, even though there are no direct contacts between these residues
and the bound Ca2+ ions. Eleven different mutants with substitutions in the
hydrophobic core were produced, and their equilibrium Ca2+-binding constants
measured from Ca2+ titrations in the presence of chromophoric chelators. The Ca2+
dissociation rate constants were estimated from Ca2+ titrations followed by 1H
NMR1 and were measured more accurately using stopped-flow fluorescence. The
parameters were measured at four KCl concentrations to assess the salt dependence
of the perturbations. The high similarity between the NMR spectra of mutants and
wild-type calbindin D9k suggests that the structure is largely unperturbed by the
substitutions. More detailed NMR investigations of the mutant in which Val61 is
substituted by Ala showed that the mutation causes only very minimal
perturbations in the immediate vicinity of residue 61. Substitutions of alanines
or glycines for bulky residues in the center of the core were found to have
significant effects on both Ca2+ affinity and dissociation rates. These
substitutions caused a reduction in affinity and an increase in off-rate. Small
effects, both increases and decreases, were observed for substitutions involving
residues far from the Ca2+ sites and toward the outer part of the hydrophobic
core. The mutant with the substitution Phe66 --> Trp behaved differently from all
other mutants, and displayed a 25-fold increase in overall affinity of binding
two Ca2+ ions and a 6-fold reduction in calcium dissociation rate. A strong
correlation (R = 0.94) was found between the observed Ca2+-dissociation rates and
affinities, as well as between the salt dependence of the off-rate and the
distance to the nearest Ca2+-coordinating atom. There was also a strong
correlation (R = 0.95) between the Ca2+ affinity and stability of the Ca2+ state
and a correlation (R = 0. 69) between the Ca2+ affinity and stability of the apo
state, as calculated from the results in the present and preceding paper in this
issue [Julenius, K., Thulin, E., Linse, S., and Finn, B. E. (1998) Biochemistry
37, 8915-8925]. The change in salt dependencies of koff and cooperativity were
most pronounced for residues completely buried in the core of the protein
(solvent accessible surface area approximately 0). Altogether, the results
suggest that the hydrophobic core residues promote Ca2+ binding both by
contributing to the preformation of the Ca2+ sites in the apo state and by
preferentially stabilizing the Ca2+-bound state.
PMID- 9636035
TI - Incorporation of tryptophan analogues into staphylococcal nuclease, its V66W
mutant, and Delta 137-149 fragment: spectroscopic studies.
AB - We have biosynthetically incorporated several tryptophan analogues into three
forms of Staphylococcal nuclease to investigate the spectroscopic characteristics
of these "intrinsic" probes and their effect on the structure of the proteins.
The set of tryptophan analogues includes 5-hydroxytryptophan, 7-azatryptophan, 4
fluorotryptophan, 5-fluorotryptophan, and 6-fluorotryptophan. 5-Hydroxytryptophan
and 7-azatryptophan have red-shifted absorbance spectra, and the latter has a red
shifted fluorescence, which is very sensitive to its environment (being heavily
quenched in water). The fluorotryptophans can serve as 19F NMR probes, and 4
fluorotryptophan has a very low fluorescence quantum yield, thus making it a
"knock-out" fluorescence analogue. The set of proteins studied includes wild-type
nuclease, which has a single tryptophan site at position 140; its V66W mutant,
which has a second tryptophan at position 66; and the Delta 137-149 fragment,
V66W', which only has a tryptophan at position 66. The environments of positions
66 and 140 are significantly different; position 140 is near the end of the long
C-terminal alpha-helix and is moderately solvent-exposed, whereas position 66 is
in the beta-barrel core region of the protein and is surrounded by apolar side
chains. Absorbance and 19F NMR spectra are used to estimate the extent of
analogue incorporation for each protein. Steady-state and time-resolved
fluorescence data are reported to characterize the emission of the analogues in
these positions in the three proteins and to develop the use of the analogues as
probes of protein structure and dynamics. Circular dichroism spectra are reported
to show that, in all but a couple of cases, the secondary structure of the
proteins containing the analogues is not significantly perturbed by the probes.
Additionally, fluorescence anisotropy decay data show the variants of wild-type
nuclease to have a rotational correlation time similar to that of tryptophan
containing nuclease.
PMID- 9636036
TI - Incorporation of tryptophan analogues into staphylococcal nuclease: stability
toward thermal and guanidine-HCl induced unfolding.
AB - The tryptophan analogues, 5-hydroxytryptophan, 7-azatryptophan, 4
fluorotryptophan, 5-fluorotryptophan, and 6-fluorotryptophan, have been
biosynthetically incorporated into Staphylococcal nuclease, its V66W mutant, and
the Delta 137-149 fragment of the latter mutant. The guanidine-HCl induced
unfolding and thermal unfolding of these proteins were studied to characterize
the effect of incorporation of these tryptophan analogues on the thermodynamic
stability of the proteins. The three proteins have tryptophan residues at
positions 140 (in wild type) and 66 (in the Delta 137-149 fragment of V66W) and
at both positions (in V66W). The unfolding data show that 5-hydroxytryptophan
does not perturb the stability of wild-type nuclease, but it destabilizes the
fragment and causes the V66W mutant to unfold in a more cooperative manner. 7
Azatryptophan is found to destabilize all three proteins. 4-Fluorotryptophan is
slightly stabilizing of the three proteins, but the other two fluorotryptophans
do not alter the stability of the proteins.
PMID- 9636037
TI - Phosphorescence and optically detected magnetic resonance characterization of the
environments of tryptophan analogues in staphylococcal nuclease, its V66W mutant,
and Delta 137-149 fragment.
AB - Phosphorescence and optically detected magnetic resonance (ODMR) measurements are
reported on the triplet states of the tryptophan analogues, 7-azatryptophan
(7AW), 5-hydroxytryptophan (5HW), and 4-, 5-, and 6-fluorotryptophan (4FW, 5FW,
6FW), when incorporated at position 140 of wild-type Staphylococcal nuclease (7AW
nuclease, etc. ), positions 66 and 140 of its V66W mutant (7AW-V66W, etc.), and
the deletion fragment of the latter, Delta 137-149 (7AW-V66W', etc.). These
measurements point to the retention of protein structure at position 140 in each
of the wild-type nuclease analogues. Substitution of the analogue at both
tryptophan sites of V66W leads to structured sites with differentiated triplet
state properties for all analogues except 7AW-V66W, whose structure is
destabilized. 5HW-V66W' is the only fragment that apparently lacks structure at
position 66. All other V66W' analogues exhibit a structured environment at
position 66 (4FW-V66W' was not studied), but in each case this site can be
differentiated readily from the corresponding site in intact V66W. 7AW-V66W' is
resolved by ODMR into two discrete structures with slightly differing zero field
splittings (ZFS). Interaction of the protein with 5HW at position 66 of 5HW-V66W
induces a 2-fold increase in the ZFS E parameter, which is reduced to its normal
value upon formation of the fragment, 5HW-V66W'. Analogous effects occur for 5FW,
but on a smaller scale.
PMID- 9636038
TI - Ionization-reactivity relationships for cysteine thiols in polypeptides.
AB - Thiol-disulfide exchange reactions are required for many aspects of cellular
metabolism including the folding of disulfide-bonded proteins, electron transfer,
and numerous regulatory mechanisms. To identify factors influencing the rates of
these reactions in polypeptides, the reactivities of Cys thiols in 16 model
peptides were measured. For each of the peptides, which contained single Cys
residues with thiol pKas ranging from 7.4 to 9.1, the rates of exchange with four
disulfide-bonded compounds were measured. In reactions with two of the disulfide
reagents, cystine and 2-hydroxyethyl disulfide, the peptide thiols displayed
Bronsted correlations between reaction rate and pKa similar to those observed
previously with model compounds (betanuc = 0.5 and 0.3, respectively). For two
reagents with net charges, oxidized glutathione and cystamine, however, the
apparent Bronsted coefficients were 0 and 0.8, respectively. These observations
are in striking contrast with those obtained with model compounds, for which the
Bronsted coefficients for the nucleophilic thiolates are largely independent of
the disulfide-containing compound. The differences in the apparent Bronsted
coefficients can be largely accounted for by electrostatic interactions between
charged groups on the peptides and disulfide reagents and demonstrate that such
interactions can play a dominant role in determining the rates of thiol-disulfide
exchange in biological molecules. The results presented here provide an improved
basis for predicting the rates of these reactions and suggest ways in which
differences in the rates of competing reactions can be either minimized, to
simplify the analysis of disulfide-coupled folding reactions, or enhanced, to
favor formation of particular disulfides.
PMID- 9636039
TI - Mutational analysis of structural features of rat hormone-sensitive lipase.
AB - Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that hydrolyzes
intracellular stores of triacylglycerols and cholesteryl esters. HSL activity is
regulated via phosphorylation-dephosphorylation, with cyclic AMP-dependent
protein kinase increasing activity following phosphorylation of a single serine
and Ca2+/calmodulin-dependent protein kinase II phosphorylating another serine at
a basal site. The current studies used site-directed mutagenesis to show that Ser
563 of rat HSL is phosphorylated by cyclic AMP-dependent protein kinase and that
Ser-565 is phosphorylated by Ca2+/calmodulin-dependent protein kinase II.
Mutation of Ser-563-->Ala eliminated HSL hydrolytic activity against cholesteryl
ester, triacylglycerol, and diacylglycerol substrates to the same extent as
mutation of Ser-423-->Ala, the presumed catalytic site. Mutation of Ser-565-->Ala
modestly decreased HSL activity. In contrast, mutation of Ser-563-->Asp preserved
HSL hydrolytic activity and even increased activity 20% above the control wild
type enzyme. Molecular modeling of the catalytic pocket of HSL suggested the
involvement of Val-710. Mutation of Val-710-->Ala resulted in an 85% loss of HSL
hydrolytic activity. The results of these studies illustrate the importance of
the presence of a hydroxyl group or negative charge at residue 563, either for
proper conformation of rat HSL or for proper stabilization of substrate to allow
maintenance of hydrolytic activity, as well as the importance of the involvement
of additional amino acids in the catalytic pocket of the enzyme.
PMID- 9636040
TI - Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of
catecholamines: evidence for a novel regulatory mechanism.
AB - The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the
affinities of catechols have been determined with both the ferric and ferrous
forms of the enzyme. Phosphorylation had no effect on the Ki value for the
inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate
of turnover was measured in assays. However, phosphorylation of the ferric enzyme
resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in
the affinity for dopamine, while the affinity for dihydroxynaphthalene was
unchanged. The changes in binding affinity for the two catecholamines were almost
exclusively due to large increases in the dissociation rate constants upon
phosphorylation. These results support a novel mechanism for regulation in which
phosphorylation affects binding of catecholamines to the catalytically inactive
ferric form of the tyrosine hydroxylase.
PMID- 9636041
TI - A null lesion in the rhodopin 3,4-desaturase of Rhodospirillum rubrum unmasks a
cryptic branch of the carotenoid biosynthetic pathway.
AB - The carotenoids accumulated by a mutant Rhodospirillum rubrum ST4, containing a
single Tn5 lesion in the pathway for carotenoid biosynthesis, were analyzed by
HPLC, 1H NMR spectroscopy, and field desorption mass spectrometry. The main
carotenoid was identified as 3,4,3',4'-tetrahydrospirilloxanthin, and the four
minor carotenoids were identified as rhodopin, 3,4-dihydroanhydrorhodovibrin, 3',
4'-dihydrorhodovibrin, and 1,1'-dihydroxylycopene. The C-3,4 and C-3',4' bonds of
all 5 carotenoids are saturated, and they have 11 conjugated double bonds. With
the exception of rhodopin, which is a normal intermediate of the wild-type
pathway, all of the carotenoids are not naturally occurring. The Tn5 lesion was
assigned to rhodopin 3,4-desaturase which is proposed to catalyze dehydrogenation
at both ends of the symmetrical spirilloxanthin derivative. An unexpected finding
was that the enzymes following rhodopin 3,4-desaturase are still able to end
modify the 3,4-, and 3',4'-saturated precursors and that the order of methylation
and hydroxylation is not obligatory. It is proposed that the observed nonnatural
carotenoids can be explained by the inclusion of a cryptic branch, unmasked by
the absence of rhodopin 3,4-desaturase, in the established linear pathway for
spirilloxanthin biosynthesis. This is the first example of latent branching of
the carotenoid biosynthesis pathway exhibited by a carotenoid mutant of a
phototrophic bacterium.
PMID- 9636042
TI - Effect of near-infrared light on the S2-state of the manganese complex of
photosystem II from Synechococcus elongatus.
AB - The Mn cluster of Photosystem II (PSII) from Synechococcus elongatus was studied
using EPR. A signal with features between g = 5 and g = 9 is reported from the S2
state. The signal is attributed to the manganese cluster in a state with a spin
5/2 state. Spectral simulations of the signal indicate zero field splitting
parameters where the |E/D| was 0.13. The new signal is formed by irradiating PSII
samples which contain the spin = 1/2 S2-state using 813 nm light below 200 K.
This effect is attributed to a spin-state change in the manganese cluster due to
absorption of the IR light by the Mn-cluster itself. The signal is similar to
that reported recently in PSII of plants [Boussac, A., Un, S., Horner, O., and
Rutherford, A. W. (1998) Biochemistry 37, 4001-4007]. In plant PSII the
comparable signal is formed at a lower temperature (optimally below 77 K), and
gradual warming of the sample in the dark leads to the formation of the state
responsible for the well-known g = 4.1 signal prior to formation of the spin 1/2
multiline signal. In the present work using cyanobacterial PSII, warming of the
sample in the dark leads to the formation of the spin 1/2 multiline signal
without formation of the g = 4 type signal as an intermediate. These observations
provide a partial explanation for the long-standing "mystery of the missing g = 4
state" in cyanobacterial PSII. The observations are rationalized in terms of
three possible states which can exist for S2: (i) the spin 1/2 multiline signal,
(ii) the state responsible for the g = 4.1 signal, and (iii) the new spin 5/2
state. The relative stability of these states differs between plants and
cyanobacteria.
PMID- 9636043
TI - The 18 kDa cytochrome c553 from Heliobacterium gestii: gene sequence and
characterization of the mature protein.
AB - The 18 kDa cytochrome c553 is the dominant c-type cytochrome in cell membranes of
Heliobacterium gestii. After solubilization, this cytochrome was purified in
three steps as a complex with two other proteins of 32 and 42 kDa. The redox
midpoint potential of the cytochrome c553 was determined to be +215 mV. The EPR
spectra clearly show the presence of an ascorbate-reducible low-spin heme with gz
= 3.048 and gy = 2.238. The gx = trough could not be detected. In addition, a
Cu(II) signal with g = 2.058 was observed, indicating that one component of the
cytochrome c553 complex contains a bound copper ion. The gene for the 18 kDa
cytochrome c553, cyhA, consists of 429 bp coding for a protein of 142 amino
acids. The association of the cytochrome with the cytoplasmic membrane is
mediated by two fatty acid molecules, one palmitate and one stearate, that could
be identified by mass spectrometry. Both fatty acids are most likely bound to the
cysteine residue of the N-terminally processed protein via a glycerol moiety. The
amino acid sequence deduced from the DNA sequence exhibits partial identity to
the membrane-bound cytochrome c551 from Bacillus PS3 [Fujiwara, Y., Oka, M.,
Hamamoto, T., and Sone, N. (1993) Biochem. Biophys. Res. Commun. 1144, 213-219]
and to the cytochrome c subunit (NorC) of the nitrous reductase from Pseudomonas
stutzeri [Zumft, W. G., Braun, C., and Cuypers, H. (1994) Eur. J. Biochem. 219,
481-490].
PMID- 9636044
TI - Monitoring the role of oxalate in manganese peroxidase.
AB - The water proton relaxation rate measurements between 0.01 and 50 MHz on water
solutions containing the cyanide adduct of the manganese-depleted manganese
peroxidase (MnP-CN-) and increasing amounts of Mn2+ have been determined. The
proton relaxivity curves have shown evidence of the formation of the protein/Mn2+
complex and have been analyzed in order to obtain spin Hamiltonian parameters and
correlation times. Oxalate is shown not to alter the above profiles. This
suggests that no protein-Mn2+-oxalate ternary complex is formed and that oxalate
does not remove Mn2+ from the protein. On the basis of high-resolution 1H NMR
experiments, we propose that Ce3+ and Gd3+ bind at the manganese site, and, on
the basis of the charge, we propose that they may mimic Mn3+. The water proton
relaxation rates of water solutions containing manganese-depleted MnP-CN- and
increasing amounts of Gd3+ have been measured and analyzed. Oxalate is shown to
remove the trivalent metal ions. This suggests that trivalent metal ions bind
oxalate and diffuse away from the protein presumably as oxalate complexes.
Implications for the enzymatic mechanism are discussed.
PMID- 9636045
TI - Ligand-induced conformational change in the ferric enterobactin receptor FepA as
studied by site-directed spin labeling and time-domain ESR.
AB - A mutant of the ferric enterobactin receptor, FepA, containing a valine to
cysteine (V338C) substitution was made and the purified protein selectively
modified with a sulfhydryl-specific nitroxide spin label. In reconstituted
liposomes, interaction of the attached spin label with a combination of water
soluble and lipid-soluble relaxation agents indicated that the V338C site was
located in the polar headgroup region of the membrane, approximately 1.5-4.5 A
above the phosphate groups of the lipids. Binding of the ligand, ferric
enterobactin (FeEnt), to the purified spin-labeled protein produced a significant
decrease in both the rotational freedom and accessibility of the nitroxide,
indicating the formation of new structural contacts between the spin label and
either the protein or the bound ligand. Electron spin-echo (ESE) measurements of
the nitroxide phase-memory relaxation rate in the presence and absence of bound
ligand showed substantial dipolar coupling between the Fe3+ of FeEnt and the spin
label and provided an iron-nitroxide distance estimate in the range of 20-30 A.
We conclude that the ligand-induced changes in spin label motion and
accessibility are due to new tertiary contacts with the protein and not to direct
contact with the ligand. These studies suggest that V338C may occupy a hinge
region connecting the ligand binding surface loop to the beta-barrel and provide
the strongest evidence to date of an in vitro ligand-induced conformational
change in FepA.
PMID- 9636046
TI - Novel branched nod factor structure results from alpha-(1-->3) fucosyl
transferase activity: the major lipo-chitin oligosaccharides from Mesorhizobium
loti strain NZP2213 bear an alpha-(1-->3) fucosyl substituent on a nonterminal
backbone residue.
AB - Mesorhizobium loti has been described as a microsymbiont of plants of the genus
Lotus. Lipo-chitin oligosaccharides (LCOs), or Nod factors, produced by several
representative M. loti strains all have similar structures. Using fast-atom
bombardment tandem mass spectrometry and NMR spectroscopy, we have now examined
the LCOs from the type strain NZP2213 and observed a much greater variety of
structures than has been described for the strains of M.loti studied previously.
Interestingly, we have identified as the major LCO a structure that bears a
fucose residue alpha-1,3-linked to the GlcNAc residue proximal to the nonreducing
terminal GlcNAc residue. This is the first time, to our knowledge, that
substitution on an internal GlcNAc residue of the LCO backbone has been observed.
This novel LCO structure suggests the presence of a novel fucosyltransferase
activity in strain NZP2213. Since the presence of this extra structure does not
have the effect of broadening the host range, we suggest that the modification of
the LCOs with a fucose residue linked to a nonterminal GlcNAc residue might
provide protection against degradation by a particular host plant enzyme (e.g., a
chitinase) or alternatively represents adaptation to a particular host-specific
receptor. The action of the alpha-(1-->3) fucosyltransferase seems to reduce
significantly the activity of NodS, the methyltransferase involved in the
addition of the N-methyl substituent to the nonreducing terminal GlcNAc residue.
An additional novel LCO structure has been identified having only a GlcNAc2
backbone. This is to our knowledge the first description of such a minimal LCO
structure.
PMID- 9636047
TI - Glutamate-459 is important for Escherichia coli branching enzyme activity.
AB - The branching enzyme belongs to the amylolytic family, a group of enzymes that
cleave and/or transfer chains of glucan. The amylolytic enzymes are homologous
and all contain four conserved regions, proposed to contain the active site. By
primary structure analysis, a conserved position unique to branching enzymes has
been identified. This residue, which is either Asp or Glu, depending on the
species, is located immediately after the putative catalytic Glu-458 (Escherichia
coli numbering). Branching enzymes differ from other amylolytic enzymes in having
this acid pair, and we asked if this motif could be essential for branching
enzyme action. We used site-directed mutagenesis of the Glu-459 residue in the E.
coli branching enzyme in order to determine the significance of the conserved
Asp/Glu in branching enzymes. A substitution of Glu-459 to Asp resulted in
increased specific activity compared to wild-type, suggesting that the mutation
had created a more efficient enzyme. Changing Glu-459 to Ala, Lys, or Gln lowered
the specific activities and altered the preferred substrate from amylose to
amylopectin.
PMID- 9636048
TI - Aspartate 221 of thymidylate synthase is involved in folate cofactor binding and
in catalysis.
AB - Structural studies indicate that Asp 221 of Lactobacilluscasei thymidylate
synthase forms a hydrogen bond network with the 2-amino and 3-imino groups of the
folate [Matthews, D. A. (1990) J. Mol. Biol. 214, 937-948; Finer-Moore, J. S.
(1990)Biochemistry 29, 6977-6986] that has been proposed to participate in
catalysis. We prepared a complete replacement set of 19 mutants at position 221
of L. casei thymidylate synthase. Of these, the only one with sufficient activity
to complement growth of a thymidylate synthase-deficient host was the Cys mutant.
To further elucidate the function of the Asp 221 side chain, seven thymidylate
synthase 221 mutants were studied in detail with regard to catalysis of dTMP
formation and of thymidylate synthase partial reactions. Most of the mutants
bound the nucleotide substrate dUMP with only moderate loss of binding affinity,
indicating that the Asp side chain does not contribute to dUMP binding. Most of
the mutants catalyzed the cofactor-independent dehalogenation of 5-bromodUMP;
hence, the Asp side chain of TS is not essential for addition of the catalytic
Cys residue to the nucleotide substrate. Mutants showed decreased affinity for
the folate cofactor, but those with side chains capable of hydrogen bond
formation were less severely affected. Some of the mutants were capable of
forming covalent thymidylate synthase-5-fluorodUMP-methylenetetrahydrofolate
complex; hence, the Asp side chain is not essential for steps leading to the
covalent complex. We conclude that the hydrogen bond network between Asp 221 and
the folate cofactor contributes to cofactor binding and a catalytic step after
formation of the covalent ternary complex intermediate.
PMID- 9636049
TI - Nucleotide and nucleoside analogues as inhibitors of cytosolic 5'-nucleotidase I
from heart.
AB - Substrate and product specificity studies were used to develop inhibitors of the
cytosolic 5'-nucleotidase I (c-N-I) from myocardium. As measured by Vmax/Km, c-N
I preferred pyrimidine 2'-deoxyribonucleotides as substrates with thymidine
monophosphate (TMP) being the most efficient. In product inhibition studies,
thymidine inhibited noncompetitively and inorganic phosphate inhibited
competitively, consistent with an ordered release of nucleoside prior to
phosphate. Mirroring nucleotide substrate specificities, pyrimidine nucleosides
were more potent product inhibitors than purine nucleosides. Thus, pyrimidine
nucleotide and nucleoside analogues were developed as inhibitors. Phosphonate
analogues of TMP were synthesized by a novel method. The most potent was the 5'
phosphonate of 3'-deoxythymidine (ddT) (apparent Ki value of 63 nM). In addition,
pyrimidine nucleoside analogues were inhibitors with 5-ethynyl-2',3'
dideoxyuridine being the most potent (apparent Ki value of 3.7 microM). The most
potent nucleotide and nucleoside inhibitor were both greater than 1000-fold more
potent inhibiting c-N-I than the cytosolic 5'-nucleotidase II. The nucleoside
analogue was also greater than 1000-fold more potent against c-N-I than the
membrane ecto-5'-nucleotidase (e-N). Because the phosphonate analogues measurably
inhibited e-N (apparent Ki values of 6-12 microM), the selectivity of the
phosphonates for c-N-I versus e-N was less (40-200-fold). Because of the high
selectivity for c-N-I versus both of the other 5'-nucleotidases, the nucleoside
inhibitors of c-N-I may be useful biochemical tools in discerning the role that c
N-I plays in generating adenosine within myocardium.
PMID- 9636050
TI - Thermodynamics of a transition state analogue inhibitor binding to Escherichia
coli chorismate mutase: probing the charge state of an active site residue and
its role in inhibitor binding and catalysis.
AB - Electrostatic interactions play important roles in the catalysis of chorismate to
prephenate by chorismate mutase. Mutation of Gln88 to glutamate in the
monofunctional chorismate mutase from Escherichia coli results in an enzyme with
a pH profile of activity significantly different from that of the wild type
protein. To investigate whether the mutation alters the substrate binding process
or the catalysis, we have directly determined the thermodynamic parameters of a
transition state analogue inhibitor binding to the wild-type chorismate mutase
and its Q88E mutant using isothermal titration calorimetry. The results
demonstrate that solvent reorganization and hydrophobic interactions contribute
the predominant free energy to inhibitor binding. The charge state of Glu88 in
the Q88E mutant was experimentally determined and was shown to be protonated at
pH 4.5 and ionized at pH 7.8, consistent with earlier hypotheses. Most
surprisingly, inhibitor binding energetics do not exhibit significant pH
dependency for both enzymes. Our findings indicate that the charge state of Glu88
has a small impact on inhibitor binding but plays an important role in the
catalytic process.
PMID- 9636051
TI - Flanking proline residues identify the L-type Ca2+ channel binding site of
calciseptine and FS2.
AB - Calciseptine and FS2 are 60-amino acid polypeptides, isolated from venom of the
black mamba (Dendroaspis polylepis polylepis), that block voltage-dependent L
type Ca2+ channels. We predicted that these polypeptides contain an identical
functional site between residues 43 and 46 by searching for proline residues that
mark the flanks of protein-protein interaction sites [Kini, R. M., and Evans, H.
J. (1966) FEBS Lett. 385, 81-86]. The predicted Ca2+ channel binding site also
occurs in closely related toxins, C10S2C2 and S4C8. Therefore, it is likely that
these toxins also will block L-type Ca2+ channels. To test the proposed binding
site on calciseptine and FS2, an eight-residue peptide, named L-calchin (L-type
calcium channel inhibitor), was synthesized and examined for biological activity.
As expected for an L-type Ca2+ channel blocker, L-calchin reduced peak systolic
and developed pressure in isolated rat heart Langendorff preparations without
affecting diastolic pressure or heart rate. Furthermore, L-calchin caused a
voltage-independent block of L-type Ca2+ channel currents in whole-cell patch
clamped rabbit ventricular myocytes. Thus the synthetic peptide exhibits the L
type Ca2+ channel blocking properties of the parent molecules, calciseptine and
FS2, but with a lower potency. These results strongly support the identification
of a site in calciseptine and FS2 that is important for binding to L-type Ca2+
channels and reinforce the importance of proline brackets flanking protein
protein interaction sites.
PMID- 9636052
TI - Purification, G protein activation, and partial amino acid sequence of a novel
phospholipase C from squid photoreceptors.
AB - Invertebrate visual signal transduction is initiated by rhodopsin activation of a
guanine nucleotide binding protein, Gq, which stimulates phospholipase C (PLC)
activity. We have previously purified a 140-kDa PLC enzyme from squid
photoreceptors that is regulated by squid Gq. In these studies, an additional PLC
enzyme was purified from the cytosol of squid photoreceptors and identified as a
70-kDa protein by SDS-polyacrylamide gel electrophoresis. Hydrolysis of
phosphatidylinositol 4,5-bisphosphate (PIP2) by PLC-70 was optimal at pH 5 in the
presence of 100 microM Ca2+ with a specific activity of 10.3 micromol min-1 mg-1.
A polyclonal antibody raised against purified PLC-70 did not recognize purified
PLC-140, and proteolytic digestion of the two purified enzymes with trypsin or
Staphylococcus aureaus V8 protease showed distinct patterns of peptide fragments,
indicating that PLC-70 is not a fragment of PLC-140. The partial amino acid
sequence of the protein showed homology with PLC21 and norpA isozymes cloned from
Drosophila, and mammalian PLC beta isozymes. Reconstitution of purified GTPgammaS
bound soluble squid Gq with PLC-70 resulted in significant enhancement of PIP2
hydrolysis over a range of Ca2+ concentrations and shifted the maximum activation
by calcium to 1 microM. These results suggest that cephalopod phototransduction
is mediated by Gq activation of more than one cytosolic PLC enzyme.
PMID- 9636053
TI - Mutations in the nucleotide-binding sites of P-glycoprotein that affect substrate
specificity modulate substrate-induced adenosine triphosphatase activity.
AB - The amino- and carboxy-terminal nucleotide-binding domains (NBD1 and NBD2) of P
glycoprotein (P-gp) share over 80% sequence identity. Almost all of NBD1 can be
exchanged by corresponding NBD2 segments with no significant loss of function,
except for a small segment around the Walker B motif. Within this segment, we
identified two sets of residues [ERGA --> DKGT (522-525) and T578C] that, when
replaced by their NBD2 counterparts, cause dramatic alterations of the substrate
specificity of the protein [Beaudet, L., and Gros, P. (1995) J. Biol. Chem. 270,
17159-17170]. We wished to gain insight into the molecular basis of this defect.
For this, we overexpressed the wild-type mouse Mdr3 and variants bearing single
or double mutations at these positions in the yeast Pichia pastoris. P-gp
specific ATPase activity was measured in yeast plasma membrane preparations after
detergent solubilization and reconstitution in Escherichia coli proteoliposomes.
P-gp proteoliposomes from P. pastoris showed a strong verapamil- and valinomycin
stimulated ATPase activity, with characteristics (KM, Vmax) similar to those
measured in mammalian cells. Mutations did not appear to affect the KM for
Mg2+ATP ( approximately 0.4 mM), but maximum velocity (Vmax) of the drug
stimulated ATPase activity was severely affected in a substrate/modulator
specific fashion. Indeed, all mutants showed complete loss of verapamil-induced
ATPase, while all retained at least some degree of valinomycin-induced ATPase
activity. Photolabeling studies with [125I]iodoarylazidoprazosin, including
competition with MDR drugs and modulators, suggested that drug binding was not
affected in the mutants. The altered drug resistance profiles of the ERGA -->
DKGT(522-525) and T578C mutants in vivo, together with the observed alterations
in substrate-induced ATPase activity of these proteins, suggest that the residues
involved may form part of a signal pathway between the membrane regions
(substrate binding) and the ATP binding sites.
PMID- 9636054
TI - Probing the "two-pronged plug two-holed socket" model for the mechanism of
binding of the Src SH2 domain to phosphotyrosyl peptides: a thermodynamic study.
AB - Src homology 2 (SH2) domains are protein modules that specifically bind to
tyrosyl phosphorylated peptides on signaling proteins. X-ray crystallographic
studies of the SH2 domain of the Src kinase have probed the mechanism of binding,
leading to the "two-pronged plug two-holed socket" mechanism whereby binding is
hypothesized to resemble a two-pronged plug (the peptide) inserting into a two
holed socket (the SH2 domain). This binding model predicts (1) a hydrophobic
basis for high-affinity binding largely determined by the level of insertion of
the third residue C-terminal to the phosphotyrosine in the peptide into a
primarily hydrophobic pocket (the +3 binding pocket) of the SH2 domain, and (2) a
binding mechanism involving no significant conformational changes in the SH2
domain. In this study, we have probed these predictions by using isothermal
titration calorimetry to extract complete thermodynamic profiles (Delta G
degrees, Delta H degrees, Delta S degrees, Delta Cp degrees) for the binding of
the Src SH2 domain to two series of tyrosyl phosphopeptides. One series consisted
of peptides that have been determined by X-ray crystallography to have different
levels of insertion of the peptide's +3 position into the +3 binding pocket. The
other series consisted of peptides with progressively smaller hydrophobic side
chains (I, L, V, and A) at the +3 position. Consistent with a binding mechanism
that does not involve substantial conformational changes, the Delta Cp degrees
values for all peptides were small and, at least for the high-affinity
interactions, similar to the Delta Cp degrees values predicted from surface area
calculations. However, unexpectedly, this study reveals that high-affinity
binding was only partially determined by the interactions between the +3 residue
in the peptide and the +3 binding pocket. Furthermore, the Delta Cp degrees
values for all peptides studied were similar, implying similar degrees of
desolvation of the +3 binding pocket upon binding. These results indicate that
the "two-pronged plug two-holed socket" model is an oversimplification of the Src
SH2 domain binding mechanism.
PMID- 9636055
TI - Calcium binding properties of an epidermal growth factor-like domain from human
thrombomodulin.
AB - Two different disulfide-paired isomers of the peptide
T422DIDECENG430GFCSGVCHNL440PGTFECISG449, spanning the junction between the fifth
and sixth EGF-like domains plus the N-terminal part of the sixth EGF-like domain
from human thrombomodulin (TM), and containing a consensus calcium binding
sequence, were synthesized and studied by two-dimensional proton NMR
spectroscopy. In the course of air oxidation of the fully reduced form of the
peptide, only uncrossed non EGF-like [1-2, 3-4] disulfide-bonded isomer was
produced, regardless of the presence of redox buffer and/or calcium. The crossed
[1-3, 2-4] isomer was prepared from a peptide with acetamidomethyl-protected
second and fourth cysteines. The isomer with the crossed disulfide pairing was a
better thrombin inhibitor and was more strongly affected by calcium binding than
the uncrossed [1-2, 3-4] isomer. Calcium-induced NMR resonance shifts observed
for the [1-3, 2-4] isomer provide evidence for the presence of a specific calcium
binding site in the corresponding TM region. There was a limited dispersion of
the proton chemical shifts and a general lack of nonsequential NOE's for both
peptide isomers in the presence or absence of calcium. Therefore, neither the apo
nor the calcium-bound forms of the peptides adopted a completely folded
conformation, despite the fact that the [1-3, 2-4] isomer contains a potential
folding nucleus existing in a number of disulfide-rich proteins. Apparently,
other interactions have to be involved to determine the three-dimensional
structure of the criss-cross fold in this peptide, most likely the interaction
with the C-terminal parts of the fifth and/or sixth EGF-like domains.
PMID- 9636056
TI - Interconversion of the ligand arrays in the CD and EF sites of oncomodulin.
Influence on Ca2+-binding affinity.
AB - The parvalbumin metal ion-binding sites differ at the +z and -x residues: Whereas
the CD site employs serine and glutamate (or aspartate), respectively, the EF
site employs aspartate and glycine. Although frequently indistinguishable in Ca2+
and Mg2+-binding assays, the CD and EF sites nonetheless exhibit markedly
different preferences for members of the lanthanide series [Williams et al.
(1984) J. Am. Chem. Soc. 106, 5698-5702], underscoring an intrinsic
nonequivalence. This nonequivalence reaches its pinnacle in the mammalian beta
parvalbumin (oncomodulin). Whereas the oncomodulin EF site exhibits the expected
Ca2+/Mg2+ signature, the Ca2+ affinity of the CD site is severely attenuated. To
obtain insight into the structural factors responsible for this reduction in
binding affinity, oncomodulin variants were examined in which the CD and EF site
ligand arrays had been exchanged. Our data suggest that binding affinity may be
dictated either by ligand identity or by the binding site environment. For
example, the Ca2+ affinity of the quasi-EF site resulting from the combined S55D
and D59G mutations is substantially lower than that of the authentic EF site.
This finding implies that other local environmental variables (e.g., binding loop
flexibility, electrostatic potentials) within the CD binding site supersede the
influence of ligand identity. However, the CD site ligand array does not acquire
a high-affinity signature when imported into the EF site, as in the D94S/G98D
variant. Instead, it retains its Ca2+-specific signature, implying that this
constellation of ligands is less sensitive to placement within the protein
molecule. The D59G and D94S single mutations substantially lower binding
affinity, consistent with removal of a liganding carboxylate. By contrast, the
S55D and G98D mutations substantially increase binding affinity, a finding at
odds with corresponding data collected on model peptide systems. Significantly,
the Ca2+ affinity of the oncomodulin CD site is increased by mutations that
weaken binding at the EF site, indicating a negatively cooperative interaction
between the two sites.
PMID- 9636057
TI - Fibrinolysis with des-kringle derivatives of plasmin and its modulation by plasma
protease inhibitors.
AB - Quantitative characterization of the interaction of des-kringle1-5-plasmin
(microplasmin) with fibrin(ogen) and plasma protease inhibitors may serve as a
tool for further evaluation of the role of kringle domains in the regulation of
fibrinolysis. Comparison of fibrin(ogen) degradation products yielded by plasmin,
miniplasmin (des-kringle1-4-plasmin), microplasmin, and trypsin on SDS gel
electrophoresis indicates that the differences in the enzyme structure result in
different rates of product formation, whereas the products of the four proteases
are very similar in molecular weight. Kinetic parameters show that plasmin is the
most efficient enzyme in fibrinogen degradation, and the kcat/KM ratio decreases
in parallel with the loss of the kringle domains. The catalytic sites of the four
proteases have similar affinities for fibrin (KM values between 0.12 and 0.21
microM). Trypsin has the highest catalytic constant for fibrin digestion (kcat =
0.47 s-1), and among plasmins with different kringle structures, the loss of
kringle5 results in a markedly lower catalytic rate constant (kcat = 0.0076 s-1
for microplasmin vs 0.048 s-1 for miniplasmin and 0.064 s-1 for plasmin). In
addition, microplasmin is inactivated by plasmin inhibitor (k" = 3.9 x 10(5) M-1
s-1) and antithrombin (k" = 1.4 x 10(3) M-1 s-1) and the rate of inactivation
decreases in the presence of fibrin(ogen). Heparin (250 nM) accelerates the
inactivation of microplasmin by antithrombin (k" = 10.5 x 10(3) M-1 s-1 ),
whereas that by plasmin inhibitor is not affected (k" = 4.2 x 10(5) M-1 s-1).
PMID- 9636058
TI - Calorimetric investigation of ethidium and netropsin binding to chicken
erythrocyte chromatin.
AB - We have investigated the thermodynamic aspects of the ligand binding to
chromatin, using isothermal titration calorimetry. Two classical DNA ligands were
used: an intercalator, ethidium bromide, and a minor groove binder, netropsin.
Stoichiometry, affinity constant, and thermodynamic parameters were determined at
various salt concentrations and different temperatures. The effect of ionic
strength was analyzed according to the Record theory applied to chromatin. We
also compared the binding parameters on naked DNA, H1/H5-depleted chromatin, and
chromatin. We demonstrated that the presence of histones on DNA still allows the
ligand binding that takes place according to a simple one single-site model. For
both ligand types, the thermodynamic driving force is enthalpic and the
association is characterized by a somewhat weaker affinity and more scattered
ligand distribution than on naked DNA. The ligand affinity is weakly altered by
the salt-induced compaction of the chromatin and the binding is accompanied by a
release of one counterion per ligand molecule. The temperature-dependent studies
revealed the existence of a small heat capacity change associated with ligand
binding to chromatin, together with an enthalpy-entropy compensation that
maintains the free energy constant over the investigated temperature range.
PMID- 9636059
TI - Sequence context profoundly influences the mutagenic potency of trans-opened
benzo[a]pyrene 7,8-diol 9,10-epoxide-purine nucleoside adducts in site-specific
mutation studies.
AB - The postoligomerization method was used to prepare oligonucleotide 16-mers that
contained dAdo or dGuo adducts, derived from trans opening of each enantiomer of
the two diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxides, in two sequence
contexts. These 16 oligonucleotides, along with the four corresponding
oligonucleotides containing unsubstituted purines, were ligated into single
stranded DNA from bacteriophage M13mp7L2 and transfected into Escherichia coli
SMH77. The mutagenic effects of replication past these adducts were then
evaluated. The various adduct isomers induced point mutations at different
frequencies and with different distributions of mutation types, as was
anticipated. However, sequence context had the most substantial effects on
mutation frequency. A high frequency of deletions of a single guanine was found
in a context where the dGuo adduct was at the 3'-end of a run of five guanines,
whereas no single base deletion was found in the other context studied, 5'-CGA
3'. Mutation frequencies in constructs containing dAdo adducts were much higher
in a 5'-TAG-3' context (37-58%, depending on the individual isomer) than in a 5'
GAT-3' context (5-20%), and for a given adduct, mutation frequency was up to 10
fold higher in the former sequence than in the latter. These findings indicate
that sequence context effects need more thorough evaluation if the goal of
understanding the mechanism through which DNA adducts lead to mutation is to be
achieved.
PMID- 9636060
TI - Rh(phen)2phi3+ as a shape-selective probe of triple helices.
AB - RNA pur*pur-pyr and pyr*pur-pyr (pur = purine, pyr = pyrimidine) triple helices
consisting of a Watson-Crick base-paired 28mer hairpin duplex and a Hoogsteen
base-paired purine or pyrimidine 12mer are targeted with photoactivated cleavage
by the metal complex Rh(phen)2phi3+ (phen = phenanthroline, phi = 9, 10
phenanthrenequinone diimine). The metal complex interacts with these triple
helices in a structure-specific manner. Different cleavage patterns are seen with
the pyr*pur-pyr and pur*pur-pyr motifs. Cleavage is seen on both of the Watson
Crick strands of the former motif and primarily on the purine Watson-Crick strand
of the latter motif. Little cleavage is seen on the Hoogsteen strand for either
motif. Importantly, the metal complex shows no detectable cleavage on the A-form
RNA duplex in the absence of the third Hoogsteen strand. The cleavage patterns
are consistent with an intercalated model for the metal complex in the triple
helix. Similar cleavage is seen on DNA triple helices, but over a background of
duplex cleavage. Targeting of synthetic RNA triple helices, but not duplex
regions, by Rh(phen)2phi3+ provides a basis for the chemical probing of triply
bonded sites in folded RNA molecules.
PMID- 9636061
TI - Multiple kinetic intermediates accumulate during the unfolding of horse
cytochrome c in the oxidized state.
AB - The unfolding kinetics of horse cytochrome c in the oxidized state has been
studied at 10, 22, and 34 degreesC as a function of guanidine hydrochloride
(GdnHCl) concentration. Rapid (millisecond) measurements of far-UV circular
dichroism (CD) as well as fluorescence quenching due to tryptophan to heme
excitation energy transfer have been used to monitor the unfolding process. At 10
degreesC, the decrease in far-UV CD signal that accompanies unfolding occurs in
two phases. The unobservable burst phase is complete within 4 ms, while the
slower phase occurs over tens to hundreds of milliseconds. The burst phase
unfolding amplitude increases cooperatively with an increase in GdnHCl
concentration, exhibiting a transition midpoint of 3.2 M at 10 degreesC. In
contrast, no burst phase change in fluorescence occurs during unfolding at 10
degreesC. At 22 and 34 degreesC, both the fluorescence-monitored unfolding
kinetics and the far-UV CD-monitored unfolding kinetics are biphasic. At both
temperatures, the two probes yield burst phase unfolding transitions that are
noncoincident with respect to the transition midpoints as well as the dependency
of the burst phase amplitudes on GdnHCl concentration. The results suggest that
at least two kinetic unfolding intermediates accumulate during unfolding. One
burst phase intermediate, IU1, has lost virtually all the native-state secondary
structure, while the other burst phase intermediate, IU2, has lost both secondary
structure and native-like compactness. The presence of kinetic unfolding
intermediates is also indicated by the nonlinear dependence of the logarithm of
the apparent unfolding rate constant on GdnHCl concentration, which is
particularly pronounced at 10 and 22 degreesC. Analysis of the burst phase
unfolding transitions obtained using the two probes shows that the stabilities of
IU1 and IU2 decrease steadily with an increase in temperature from 10 to 34
degreesC, suggesting that the structures present in them are stabilized
principally by hydrogen bonding interactions.
PMID- 9636062
TI - Secondary tritium and solvent deuterium isotope effects as a probe of the
reaction catalyzed by porcine recombinant dihydropyrimidine dehydrogenase.
AB - Dihydropyrimidine dehydrogenase catalyzes the rate-limiting step in the
degradation of pyrimidines in mammals, the reduction of uracil or thymine to
their 5,6-dihydro derivatives. The reduction of uracil by enzyme-bound reduced
flavin involves both proton and hydride transfer. In order to determine whether
hydride and proton transfer occur in a concerted or stepwise fashion, and to
determine the nature of the transition state for the reduction, secondary tritium
kinetic isotope effects were measured in H2O and D2O. The tritium isotope effect
using 5-3H-uracil is 0.90 +/- 0.03 in H2O and becomes more inverse, 0.85 +/-
0.04, in D2O. Data are interpreted in terms of a stepwise reduction at C-6
followed by protonation at C-5. A late transition state is proposed for the
proton transfer at C-5 of uracil.
PMID- 9636063
TI - A reversibly unfolding fragment of P22 tailspike protein with native structure:
the isolated beta-helix domain.
AB - The homotrimeric tailspike endorhamnosidase of phage P22 has been used to compare
in vivo and in vitro folding pathways and the influence of single amino acid
substitutions thereon. Its main structural motif, which contains the known
folding mutation sites, consists of three large right-handed parallel beta
helices. A thermodynamic analysis of the stability of tailspike is prevented by
the irreversibility of unfolding at high temperatures or high concentrations of
denaturant, probably due to interdigitation of the domains neighboring the beta
helix. We therefore expressed and isolated a tailspike fragment comprising only
its central beta-helix domain (residues 109-544). As shown by equilibrium
ultracentrifugation, the isolated beta-helix is a monomer at concentrations below
1 microM and trimerizes reversibly at higher protein concentrations. Both the
similarity of fluorescence and CD spectra, compared to the complete protein, and
the specific binding and hydrolysis of substrate suggest a nativelike structure.
Moreover, urea denaturation transitions of the beta-helix domain are freely
reversible, providing the basis for a future quantitative analysis of the effects
of the folding mutations on the thermodynamic stability of the domain and of
structural features responsible for folding and stability of the parallel beta
helix motif in general.
PMID- 9636064
TI - NMR study of the conformation and localization of porcine galanin in SDS
micelles. Comparison with an inactive analog and a galanin receptor antagonist.
AB - Galanin is a 29/30-residue neuro-endocrine peptide which performs its many
important physiological functions via a membrane-bound receptor. By using two
dimensional proton NMR spectroscopy, complete relaxation matrix analysis, and
simulated annealing, the conformation of porcine galanin was determined in a
membrane-mimicking solvent containing sodium dodecyl sulfate (SDS) micelles. The
final family of calculated structures displays three well-defined beta- or gamma
turn regions, comprising residues 1-5, 7-10, and 24-27, but has otherwise a
random conformation. The receptor-interacting N-terminal part, residues 1-5, was
found to be best defined with a backbone RMSD value of 0.12 A. The mode of
association between galanin and the SDS micelle was determined by observing the
broadening effect on proton resonances, when spin-labeled 5- and 12-doxyl
stearate molecules were added. It was concluded that galanin is located close to
the surface of the micelle with two regions, residues 6-9 and 24-29, as well as
two single residues, 18 and 21, reaching out into the aqueous solvent. Additional
NMR studies were carried out on an inactive analogue, Ala2-galanin, and an
antagonist M40. The results show that the proton resonances of galanin and M40
have identical chemical shifts in the N-terminal receptor-interacting region,
indicating similar solution structures in this region. For Ala2-galanin, the same
region displays a spectral heterogeneity with chemical shifts clearly different
from the other two peptides, indicative of different secondary structures. These
results may provide a structural background for the antagonist activity of M40
and the hormonal inactivity of Ala2-galanin, as compared to galanin.
PMID- 9636065
TI - Folding kinetics of a fluorescent variant of monomeric lambda repressor.
AB - A tryptophan-containing variant of monomeric lambda repressor has been made, and
its folding kinetics were analyzed at 20 degreesC using fluorescence stopped-flow
and dynamic NMR. Equilibrium denaturation curves obtained by circular dichroism,
fluorescence, and NMR are superimposable. Stopped-flow analysis indicates that in
the absence of denaturants the folding reaction is complete within the dead-time
of the experiment. Within higher denaturant conditions, where the folding rate is
slower, NMR and stopped-flow agree on the folding and unfolding rates of the
protein. In 3.4 M urea and 1.8 M GdmCl, we show that the variant folds within 2
ms. Extrapolation indicates that the folding time is 20 micro(s) in the absence
of denaturants. All folding and unfolding reactions displayed monoexponential
kinetics, and no burst-phases were observed. In addition, the thermodynamic
parameters Delta G and meq obtained from the kinetic analysis are consistent with
the equilibrium experiments. The results support a two-state Dleft and right
arrow N folding model.
PMID- 9636066
TI - A semiconserved residue inhibits complex formation by stabilizing interactions in
the free state of a theophylline-binding RNA.
AB - The theophylline-binding RNA aptamer contains a 15 nucleotide motif that is
required for high-affinity ligand binding. One residue within this RNA motif is
only semiconserved and can be an A or C. This residue, C27, was disordered in the
previously determined three-dimensional structure of the complex, suggesting that
it is dynamic in solution. 13C Relaxation measurements are reported here,
demonstrating that C27 is highly dynamic in the otherwise well-ordered RNA
theophylline complex. A synthetic complex with an abasic residue at position 27
was found to exhibit wild-type binding affinity (Kd approximately 0.2 microM),
indicating that the base of residue 27 is not directly involved with theophylline
binding. Surprisingly, the U27 and G27 RNAs were found to bind theophylline with
low affinity (Kd values > 4 microM). NMR spectroscopy on the U27 RNA revealed the
presence of an A7-U27 base pair in the free RNA that prevents formation of a
critical base-platform structural motif and therefore blocks theophylline
binding. Similarly, a protonated A7H+-C27 base pair forms in the absence of
theophylline at low pH, which explains the unusual pH dependence of theophylline
binding of the C27 RNA aptamer. Thus the weak binding for various nucleotides at
position 27 arises not from unfavorable interactions in the RNA-theophylline
complex but instead from stable interactions in the free state of the RNA that
inhibit theophylline binding.
PMID- 9636067
TI - Strong selective pressure to use G:U to mark an RNA acceptor stem for alanine.
AB - The identity of alanine tRNAs is dependent on a G:U base pair at the 3:70
position of the acceptor helix. This system of molecular recognition is widely
distributed from bacteria to human-cell cytoplasm. In contrast, some
mitochondrial alanine acceptor helices are markedly different and contain
nucleotides known to block aminoacylation by a nonmitochondrial enzyme. Thus,
acceptor helix recognition may differ in these systems and may not depend on G:U.
Here we report an example of a Caenorhabditis elegans mitochondrial system where
the G:U pair is preserved but where proximal nucleotides known to block charging
by a nonmitochondrial enzyme are also present. We show that, as expected, the
mitochondrial substrate is not charged by the bacterial enzyme. In contrast, the
cloned mitochondrial enzyme charged both mitochondrial and bacterial
microhelices. Strikingly, charging of each required the G:U pair. Thus, G:U
recognition persists even with an acceptor helix context that inactivates
nonmitochondrial systems. The results suggest strong selective pressure to use
G:U in a variety of contexts to mark an acceptor stem for alanine. Separate
experiments also demonstrate that, at least for the mitochondrial enzyme, helix
instability or irregularity is not important for recognition of G:U.
PMID- 9636068
TI - Secretory phospholipase A2 and lipoprotein lipase enhance 15-lipoxygenase-induced
enzymic and nonenzymic lipid peroxidation in low-density lipoproteins.
AB - The oxidation of low-density lipoprotein (LDL) is thought to contribute to
atherogenesis. 15-Lipoxygenase (15LO) induces LDL oxidation, and phospholipase A2
enhances this process [Sparrow, C. P. , Parthasarathy, S., and Steinberg, D.
(1988) J. LipidRes. 29, 745-753]. As the underlying mechanism of the enhancing
effect has not been investigated previously, we here show that in the presence of
soybean 15LO (SLO) or human 15LO (rhLO), the addition of lipoprotein lipase,
porcine pancreatic, or human type IIa secretory phospholipase A2 (sPLA2) greatly
enhanced the accumulation of hydro(pero)xides of all major classes of LDL's
lipids. Hydroperoxides of free fatty acids accumulated exclusively as enzymic
products with kinetics reflecting both the formation of free fatty acids and the
initial 'build-up' of alpha-tocopheroxyl radical. In contrast, hydroperoxides of
cholesteryl esters and phosphatidylcholine accumulated linearly over
comparatively longer periods of time and, in the case of rhLO, well beyond
inactivation of the oxygenase. With SLO, formation of oxidized esterified lipids
occurred nonenzymically, independent of the presence of lipase and despite the
oxygenase remaining active until the end of the incubation. Enhancement of rhLO
induced LDL lipid peroxidation by sPLA2 was eliminated by a neutralizing anti
sPLA2 antibody, indicating that lipolytic activity was required for this effect.
LDL depleted of alpha-tocopherol was resistant to oxidation by 15LO alone,
whereas lipase overcame this resistance, demonstrating that lipases enhance 15LO
induced enzymic and nonenzymic peroxidation of LDL lipids. This is likely due to
provision of free fatty acid substrate, resulting in an enhanced rate of free
radical formation which itself causes nonenzymic peroxidation of esterified
lipids. As lipases and 15LO are present in atherosclerotic lesions, our findings
could be of pathophysiological significance.
PMID- 9636069
TI - Diminished Sonic hedgehog signaling and lack of floor plate differentiation in
Gli2 mutant mice.
AB - Floor plate cells at the midline of the neural tube are specified by high-level
activity of Sonic hedgehog (Shh) secreted by notochord, whereas motor neurons are
thought to be specified by a lower level activity of Shh secreted in turn by
floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus
functions as a transcription factor activating Hedgehog-responsive genes. We
report that the expression of known Shh-responsive genes such as Ptc and Gli1 is
downregulated in mutant mice lacking Gli2 function. Gli2 mutants fail to develop
a floor plate yet still develop motor neurons, which occupy the ventral midline
of the neural tube. Our results imply that Gli2 is required to mediate high level
but not low level Shh activity and show that the development of motor neurons can
occur in the absence of floor plate induction.
PMID- 9636070
TI - The WIGGUM gene is required for proper regulation of floral meristem size in
Arabidopsis.
AB - The study of cell division control within developing tissues is central to
understanding the processes of pattern formation. The floral meristem of
angiosperms gives rise to floral organs in a particular number and pattern.
Despite its critical role, little is known about how cell division is controlled
in the floral meristem, and few genes involved have been identified. We describe
the phenotypic effects of mutations in WIGGUM, a gene required for control of
cell proliferation in the floral and apical meristem of Arabidopsis thaliana.
wiggum flowers contain more organs, especially sepals and petals, than found in
wild-type flowers. This organ number phenotype correlates with specific size
changes in the early floral meristem, preceding organ initiation. Genetic studies
suggest that WIGGUM acts on a similar process but in a separate pathway than the
CLAVATA1 and CLAVATA3 genes in meristem size regulation, and reveal interactions
with other genes affecting meristem structure and identity. Analysis of double
mutant phenotypes also reveals a role for WIGGUM in apical meristem function. We
propose that WIGGUM plays a role in restricting cell division relative to
cellular differentiation in specific regions of the apical and floral meristems.
PMID- 9636071
TI - Pattern formation and growth during floral organogenesis: HUELLENLOS and
AINTEGUMENTA are required for the formation of the proximal region of the ovule
primordium in Arabidopsis thaliana.
AB - Our understanding of the molecular mechanisms that regulate and integrate the
temporal and spatial control of cell proliferation during organ ontogenesis,
particularly of floral organs, continues to be primitive. The ovule, the
progenitor of the seed, of Arabidopsis thaliana has been used to develop an
effective model system for the analysis of plant organogenesis. A typical feature
of a generalized ovule is the linear arrangement of at least three distinct
elements, the funiculus, chalaza and nucellus, along a proximal-distal axis. This
pattern is supposed to be established during the early proliferative phase of
ovule development. We provide genetic evidence that the young ovule primordium
indeed is a composite structure. Two genes, HUELLENLOS and AINTEGUMENTA have
overlapping functions in the ovule and differentially control the formation of
the central and proximal elements of the primordium. The results indicate that
proximal-distal pattern formation in the Arabidopsis ovule takes place in a
sequential fashion, starting from the distal end. Furthermore, we show that
HUELLENLOS also regulates the initiation and/or maintenance of integument and
embryo sac ontogenesis and interestingly prevents inappropriate cell death in the
young ovule.
PMID- 9636072
TI - Identification and analysis of a gene that is essential for morphogenesis and
prespore cell differentiation in Dictyostelium.
AB - We have identified a gene (PslA) that is expressed throughout Dictyostelium
development and encodes a novel protein that is required for proper aggregation
and subsequent cell-type differentiation and morphogenesis. pslA null (pslA-)
cells produce large aggregation streams under conditions in which wild-type cells
form discrete aggregates. Tips form along the stream, elongate to produce a
finger, and eventually form a terminal structure that lacks a true sorus (spore
head). More than half of the cells remain as a mass at the base of the developing
fingers. The primary defect in the pslA- strain is the inability to induce
prespore cell differentiation. Analyses of gene expression show a complete lack
of prespore-specific gene expression and no mature spores are produced. In
chimeras with wild-type cells, pslA- cells form the prestalk domain and normal,
properly proportioned fruiting bodies can be produced. This indicates that pslA-
cells are able to interact with wild-type cells and regulate patterning, even
though pslA- cells are unable to express prespore cell-type-specific genes, do
not participate in prespore cell differentiation and do not produce pslA- spores
in the chimeras. While pslA- cells produce mature, vacuolated stalk cells during
multicellular development, pslA- cells are unable to do so in vitro in response
to exogenous DIF (a morphogen required for prestalk and stalk cell
differentiation). These results indicate that pslA- cells exhibit a defect in the
prestalk/stalk cell pathways under these experimental conditions. Our results
suggest that PslA's primary function is to regulate prespore cell determination
very early in the prespore pathway via a cell-autonomous mechanism, possibly at
the time of the initial prestalk/prespore cell-fate decision. Indirect
immunofluorescence of myc-tagged PslA localizes the protein to the nucleus,
suggesting that PslA may function to control the prespore pathway at the level of
transcription.
PMID- 9636073
TI - A novel Xenopus mix-like gene milk involved in the control of the endomesodermal
fates.
AB - Here we describe a novel Xenopus homeobox gene, milk, related by sequence
homology and expression pattern to the vegetally expressed Mix.1. As is the case
with Mix.1, milk is an immediate early response gene to the mesoderm inducer
activin. milk is expressed at the early gastrula stage in the vegetal cells,
fated to form endoderm, and in the marginal zone fated to form mesoderm. During
gastrulation, expression of milk becomes progressively reduced in the involuting
mesodermal cells but is retained in the endoderm, suggesting that it may play a
key role in the definition of the endo-mesodermal boundary in the embryo.
Overexpression of milk in the marginal zone blocks mesodermal cell involution,
represses the expression of several mesodermal genes such as Xbra, goosecoid,
Xvent-1 or Xpo and increases the expression of the endodermal gene, endodermin.
In the dorsal marginal zone, overexpression of milk leads to a severe late
phenotype including the absence of axial structures. Ectopic expression of milk
in the animal hemisphere or in ectodermal explants induces a strong expression of
endodermin. Taken together, we propose that milk plays a role in the correct
patterning of the embryo by repressing mesoderm formation and promoting endoderm
identity.
PMID- 9636074
TI - Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during
development of the branchial area.
AB - In Hoxa-2(-/- )embryos, the normal skeletal elements of the second branchial arch
are replaced by a duplicated set of first arch elements. We show here that Hoxa-2
directs proper skeletal formation in the second arch by preventing chondrogenesis
and intramembranous ossification. In normal embryos, Hoxa-2 is expressed
throughout the second arch mesenchyme, but is excluded from the chondrogenic
condensations. In the absence of Hoxa-2, chondrogenesis is activated ectopically
within the rostral Hoxa-2 expression domain to form the mutant set of cartilages.
In Hoxa-2(-/- )embryos the Sox9 expression domain is shifted into the normal Hoxa
2 domain. Misexpression of Sox9 in this area produces a phenotype resembling that
of the Hoxa-2 mutants. These results indicate that Hoxa-2 acts at early stages of
the chondrogenic pathway, upstream of Sox9 induction. We also show that Hoxa-2
inhibits dermal bone formation when misexpressed in its precursors. Furthermore,
molecular analyses indicate that Cbfa1 is upregulated in the second branchial
arches of Hoxa-2 mutant embryos suggesting that prevention of Cbfa1 induction
might mediate Hoxa-2 inhibition of dermal bone formation during normal second
arch development. The implications of these results on the patterning of the
branchial area are discussed.
PMID- 9636075
TI - Vax1 is a novel homeobox-containing gene expressed in the developing anterior
ventral forebrain.
AB - The vertebrate forebrain is formed at the rostral end of the neural plate under
the regulation of local and specific signals emanating from both the endomesoderm
and neuroectoderm. The development of the rostral and ventral forebrain in
particular was difficult to study, mainly because no specific markers are
available to date. Here, we report the identification of Vax1, a novel homeobox
containing gene identified in mouse, Xenopus and human. It is closely related to
members of the Not and Emx gene families, all of which are required for the
formation of structures where they are expressed. In mouse and Xenopus, Vax1
expression first occurs in the rostral neural plate, in the medial anterior
neural ridge and adjacent ectoderm. Later, at midgestation in the mouse and
tadpole stage in Xenopus, the expression remains confined in the derivatives of
this territory which differentiate into rostromedial olfactory placode, optic
nerve and disc, and anterior ventral forebrain. Together, these observations
suggest that Vax1 could have an early evolutionary origin and could participate
in the specification and formation of the rostral and ventral forebrain in
vertebrates. Comparison of the limits of the expression territory of Vax1 with
that of Dlx1, Pax6 and Emx1 indicates that the corticostriatal ridge is a complex
structure with distinct identifiable genetic compartments. Besides, the study of
Vax1 expression in Pax6-deficient homozygous brains indicates that its regulation
is independent of Pax6, although the expression patterns of these two genes
appear complementary in wild-type animals. Vax1 chromosomal location is mapped at
the distal end of the mouse chromosome 19, linked with that of Emx2. These two
genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting
new tool to study the rostral ventral forebrain patterning, morphogenesis and
evolution as well as the terminal differentiation of the forebrain in mouse and
Xenopus.
PMID- 9636076
TI - SCL specifies hematopoietic mesoderm in Xenopus embryos.
AB - Targeted gene disruption experiments in the mouse have demonstrated an absolute
requirement for several transcription factors for the development of
hematopoietic progenitors during embryogenesis. Disruption of the basic helix
loop-helix gene SCL (stem cell leukemia) causes a block early in the
hematopoietic program with defects in all hematopoietic lineages. To understand
how SCL participates in the organogenesis of blood, we have isolated cDNAs
encoding Xenopus SCL and characterized the function of SCL during embryogenesis.
We demonstrate that SCL is expressed in ventral mesoderm early in embryogenesis.
SCL expression is induced by BMP-4, and a dominant negative BMP-4 receptor
inhibits SCL expression in the ventral region of the embryo. Expression of SCL in
either bFGF-treated animal pole explants or dorsal marginal zone explants leads
to the expression of globin protein. Furthermore, over-expression of SCL does not
alter normal dorsal-ventral patterning in the embryo, indicating that SCL acts to
specify mesoderm to a hematopoietic fate after inductive and patterning events
have occurred. We propose that SCL is both necessary and sufficient to specify
hematopoietic mesoderm, and that it has a similar role in specifying
hematopoietic cell fate as MyoD has in specifying muscle cell fate.
PMID- 9636077
TI - Role of laminin polymerization at the epithelial mesenchymal interface in
bronchial myogenesis.
AB - Undifferentiated mesenchymal cells were isolated from mouse embryonic lungs and
plated at subconfluent and confluent densities. During the first 5 hours in
culture, all the cells were negative for smooth muscle markers. After 24 hours in
culture, the mesenchymal cells that spread synthesized smooth muscle alpha-actin,
muscle myosin, desmin and SM22 in levels comparable to those of mature smooth
muscle. The cells that did not spread remained negative for smooth muscle
markers. SM differentiation was independent of cell-cell contact or
proliferation. In additional studies, undifferentiated lung mesenchymal cells
were cocultured with lung embryonic epithelial cells at high density. The
epithelial cells aggregated into cysts surrounded by mesenchymal cells and a
basement membrane was formed between the two cell types. In these cocultures, the
mesenchymal cells in contact with the basement membrane spread and differentiated
into smooth muscle. The rest of the mesenchymal cells remained round and negative
for smooth muscle markers. Inhibition of laminin polymerization by an antibody to
the globular regions of laminin beta1/gamma1 chains blocked basement membrane
assembly, mesenchymal cell spreading and smooth muscle differentiation. These
studies indicated that lung embryonic mesenchymal cells have the potential to
differentiate into smooth muscle and the process is triggered by their spreading
along the airway basement membrane.
PMID- 9636078
TI - Two domains in vertebral development: antagonistic regulation by SHH and BMP4
proteins.
AB - It has previously been shown that the notochord grafted laterally to the neural
tube enhances the differentiation of the vertebral cartilage at the expense of
the derivatives of the dermomyotome. In contrast, the dorsomedial graft of a
notochord inhibits cartilage differentiation of the dorsal part of the vertebra
carrying the spinous process. Cartilage differentiation is preceded by the
expression of transcription factors of the Pax family (Pax1/Pax9) in the
ventrolateral domain and of the Msx family in the dorsal domain. The
proliferation and differentiation of Msx-expressing cells in the dorsal
precartilaginous domain of the vertebra are stimulated by BMP4, which acts
upstream of Msx genes. It has previously been shown that the SHH protein arising
from the notochord (and floor plate) is necessary for the survival and further
development of Pax1/Pax9-expressing sclerotomal cells. We show here that SHH acts
antagonistically to BMP4. SHH-producing cells grafted dorsally to the neural tube
at E2 inhibit expression of Bmp4 and Msx genes and also inhibits the
differentiation of the spinous process. We present a model that accounts for
cartilage differentiation in the vertebra.
PMID- 9636079
TI - hermaphrodite and doublesex function both dependently and independently to
control various aspects of sexual differentiation in Drosophila.
AB - The hermaphrodite (her) gene is necessary for sexual differentiation in
Drosophila. Our characterization of her's zygotic function suggests that one set
of female-specific terminal differentiation genes, the yolk protein (yp) genes,
is transcriptionally activated by two separate pathways. One is a female-specific
pathway, which is positively regulated by the female-specific doublesex protein
(DSXF). The other is a non-sex-specific pathway, that is positively regulated by
HER. The HER pathway is prevented from functioning in males by the action of the
male-specific doublesex protein (DSXM). The HER and DSX pathways also function
independently to control downstream target genes in the precursor cells that give
rise to the vaginal teeth and dorsal anal plate of females, and the lateral anal
plates of males. However, a female-specific pathway that is dependent on both
DSXF and HER controls the female-specific differentiation of the foreleg bristles
and tergites 5 and 6, and the male-specific differentiation of these tissues does
not require the suppression of HER's function by DSXM.
PMID- 9636080
TI - Ecdysone pathway is required for furrow progression in the developing Drosophila
eye.
AB - In Drosophila, secretion of the steroid hormone ecdysone from the prothoracic
ring gland coordinates and triggers events such as molting and metamorphosis. In
the developing Drosophila compound eye, pattern formation and cell-type
specification initiate at a moving boundary known as the morphogenetic furrow. We
have investigated the role of ecdysone in eye development and report here that
the ecdysone signaling pathway is required for progression of the morphogenetic
furrow in the eye imaginal disc of Drosophila. Genetic disruption both of the
ecdysone signal in vivo with the ecdysoneless1 (ecd1) mutant and of ecdysone
response with a Broad-Complex mutant result in disruption of morphogenetic furrow
progression. In addition, we show that ecdysone-dependent gene expression, both
of a reporter of transcriptional activity of the Ecdysone Receptor and of the Z1
isoform of the Broad Complex, are localized in and close to the furrow. These
results suggest that, in the morphogenetic furrow, temporal hormonal signals are
integrated into genetic pathways specifying spatial pattern.
PMID- 9636081
TI - Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during
mouse gonadal development and is a potent activator of the Mullerian inhibiting
substance promoter.
AB - Mammalian gonadal development and sexual differentiation are complex processes
that require the coordinated expression of a specific set of genes in a strict
spatiotemporal manner. Although some of these genes have been identified, the
molecular pathways, including transcription factors, that are critical for the
early events of lineage commitment and sexual dimorphism, remain poorly
understood. GATA-4, a member of the GATA family of transcription factors, is
present in the gonads and may be a regulator of gonadal gene expression. We have
analyzed the ontogeny of gonadal GATA-4 expression by immunohistochemistry. GATA
4 protein was detected as early as embryonic day 11.5 in the primitive gonads of
both XX and XY mouse embryos. In both sexes, GATA-4 specifically marked the
developing somatic cell lineages (Sertoli in testis and granulosa in ovary) but
not primordial germ cells. Interestingly, abundant GATA-4 expression was
maintained in Sertoli cells throughout embryonic development but was markedly
down-regulated shortly after the histological differentiation of the ovary on
embryonic day 13.5. This pattern of expression suggested that GATA-4 might be
involved in early gonadal development and possibly sexual dimorphism. Consistent
with this hypothesis, we found that the Mullerian inhibiting substance promoter
which harbors a conserved GATA element is a downstream target for GATA-4. Thus,
transcription factor GATA-4 may be a new factor in the cascade of regulators that
control gonadal development and sex differentiation in mammals.
PMID- 9636082
TI - Mutant Vg1 ligands disrupt endoderm and mesoderm formation in Xenopus embryos.
AB - The Xenopus Vg1 gene, a TGFbeta superfamily member, is expressed as a maternal
mRNA localized to prospective endoderm, and mature Vg1 protein can induce both
endodermal and mesodermal markers in embryonic cells. Most previous work on
embryonic inducers, including activin, BMPs and Vg1, has relied on ectopic
expression to assay for gene function. Here we employ a mutant ligand approach to
block Vg1 signaling in developing embryos. The results indicate that Vg1
expression is essential for normal endodermal development and the induction of
dorsal mesoderm in vivo.
PMID- 9636083
TI - Frizzled-8 is expressed in the Spemann organizer and plays a role in early
morphogenesis.
AB - Wnts are secreted signaling molecules implicated in a large number of
developmental processes. Frizzled proteins have been identified as likely
receptors for Wnt ligands in vertebrates and invertebrates, but a functional role
for vertebrate frizzleds has not yet been defined. To assess the endogenous role
of frizzled proteins during vertebrate development, we have identified and
characterized a Xenopus frizzled gene (xfz8). It is highly expressed in the deep
cells of the Spemann organizer prior to dorsal lip formation and in the early
involuting marginal zone. Ectopic expression of xfz8 in ventral cells leads to
complete secondary axis formation and can synergize with Xwnt-8 while an
inhibitory form of xfz8 (Nxfz8) blocks axis duplication by Xwnt-8, consistent
with a role for xfz8 in Wnt signal transduction. Expression of Nxfz8 in dorsal
cells has profound effects on morphogenesis during gastrulation and neurulation
that result in dramatic shortening of the anterior-posterior axis. Our results
suggest a role for xfz8 in morphogenesis during the gastrula stage of
embryogenesis.
PMID- 9636084
TI - Isolation and developmental expression of the amphioxus Pax-6 gene (AmphiPax-6):
insights into eye and photoreceptor evolution.
AB - Pax-6 genes have been identified from a broad range of invertebrate and
vertebrate animals and shown to be always involved in early eye development.
Therefore, it has been proposed that the various types of eyes evolved from a
single eye prototype, by a Pax-6-dependent mechanism. Here we describe the
characterization of a cephalochordate Pax-6 gene. The single amphioxus Pax-6 gene
(AmphiPax-6) can produce several alternatively spliced transcripts, resulting in
proteins with markedly different amino and carboxy termini. The amphioxus Pax-6
proteins are 92% identical to mammalian Pax-6 proteins in the paired domain and
100% identical in the homeodomain. Expression of AmphiPax-6 in the anterior
epidermis of embryos may be related to development of an olfactory epithelium.
Expression is also detectable in Hatschek's left diverticulum as it forms the
preoral ciliated pit, part of which gives rise to the homolog of the vertebrate
anterior pituitary. A zone of expression in the anterior neural plate of early
embryos is carried into the cerebral vesicle (a probable diencephalic homolog)
during neurulation. This zone includes cells that will differentiate into the
lamellar body, a presumed homolog of the vertebrate pineal eye. In neurulae,
AmphiPax-6 is also expressed in ventral cells at the anterior tip of the nerve
cord; these cells are precursors of the photoreceptive neurons of the frontal
eye, the presumed homolog of the vertebrate paired eyes. However, AmphiPax-6
expression was not detected in two additional types of photoreceptors, the Joseph
cells or the organs of Hesse, which are evidently relatively recent adaptations
(ganglionic photoreceptors) and appear to be rare exceptions to the general rule
that animal photoreceptors develop from a genetic program triggered by Pax-6.
PMID- 9636085
TI - Mutations in mouse Aristaless-like4 cause Strong's luxoid polydactyly.
AB - Mutations that affect vertebrate limb development provide insight into pattern
formation, evolutionary biology and human birth defects. Patterning of the limb
axes depends on several interacting signaling centers; one of these, the zone of
polarizing activity (ZPA), comprises a group of mesenchymal cells along the
posterior aspect of the limb bud that express sonic hedgehog (Shh) and plays a
key role in patterning the anterior-posterior (AP) axis. The mechanisms by which
the ZPA and Shh expression are confined to the posterior aspect of the limb bud
mesenchyme are not well understood. The polydactylous mouse mutant Strong's
luxoid (lst) exhibits an ectopic anterior ZPA and expression of Shh that results
in the formation of extra anterior digits. Here we describe a new chlorambucil
induced deletion allele, lstAlb, that uncovers the lst locus. Integration of the
lst genetic and physical maps suggested the mouse Aristaless-like4 (Alx4) gene,
which encodes a paired-type homeodomain protein that plays a role in limb
patterning, as a strong molecular candidate for the Strong's luxoid gene. In
genetic crosses, the three lst mutant alleles fail to complement an Alx4 gene
targeted allele. Molecular and biochemical characterization of the three lst
alleles reveal mutations of the Alx4 gene that result in loss of function. Alx4
haploinsufficiency and the importance of strain-specific modifiers leading to
polydactyly are indicative of a critical threshold requirement for Alx4 in a
genetic program operating to restrict polarizing activity and Shh expression in
the anterior mesenchyme of the limb bud, and suggest that mutations in Alx4 may
also underlie human polydactyly.
PMID- 9636086
TI - TGF-beta/BMP superfamily members, Gbb-60A and Dpp, cooperate to provide pattern
information and establish cell identity in the Drosophila wing.
AB - Within a developing organism, cells receive many signals which control their
proliferation, fate specification and differentiation. One group of such proteins
is the TGF-beta/BMP class of related signaling molecules. Based on expression
studies, multiple members of this class of ligands must impinge upon the same
cells of a developing tissue; however, the role that multiple TGF-beta/BMP
ligands may play in directing the development of such a tissue is not understood.
Here we provide evidence that multiple BMPs are required for growth and
patterning of the Drosophila wing. The Drosophila BMP gene, gbb-60A, exhibits a
requirement in wing morphogenesis distinct from that shown previously for dpp, a
well-characterized Drosophila BMP member. gbb-60A mutants exhibit a loss of
pattern elements from the wing, particularly those derived from cells in the
posterior compartment, consistent with the gbb-60A RNA and protein expression
pattern. Based on genetic analysis and expression studies, we conclude that Gbb
60A must signal primarily as a homodimer to provide patterning information in the
wing imaginal disc. We demonstrate that gbb-60A and dpp genetically interact and
that specific aspects of this interaction are synergistic while others are
antagonistic. We propose that the positional information received by a cell at a
particular location within the wing imaginal disc depends on the balance of Dpp
to Gbb-60A signaling. Furthermore, the critical ratio of Gbb-60A to Dpp signaling
appears to be mediated by both Tkv and Sax type I receptors.
PMID- 9636087
TI - Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory
sequence that governs Wnt-1 expression in the murine neural plate.
AB - The generation of anterior-posterior polarity in the vertebrate brain requires
the establishment of regional domains of gene expression at early somite stages.
Wnt-1 encodes a signal that is expressed in the developing midbrain and is
essential for midbrain and anterior hindbrain development. Previous work
identified a 5.5 kilobase region located downstream of the Wnt-1 coding sequence
which is necessary and sufficient for Wnt-1 expression in vivo. Using a
transgenic mouse reporter assay, we have now identified a 110 base pair
regulatory sequence within the 5.5 kilobase enhancer, which is sufficient for
expression of a lacZ reporter in the approximate Wnt-1 pattern at neural plate
stages. Multimers of this element driving Wnt-1 expression can partially rescue
the midbrain-hindbrain phenotype of Wnt-1(-/-) embryos. The possibility that this
region represents an evolutionarily conserved regulatory module is suggested by
the identification of a highly homologous region located downstream of the wnt-1
gene in the pufferfish (Fugu rubripes). These sequences are capable of
appropriate temporal and spatial activation of a reporter gene in the embryonic
mouse midbrain; although, later aspects of the Wnt-1 expression pattern are
absent. Genetic evidence has implicated Pax transcription factors in the
regulation of Wnt-1. Although Pax-2 binds to the 110 base pair murine regulatory
element in vitro, the location of the binding sites could not be precisely
established and mutation of two putative low affinity sites did not abolish
activation of a Wnt-1 reporter transgene in vivo. Thus, it is unlikely that Pax
proteins regulate Wnt-1 by direct interactions with this cis-acting regulatory
region. Our analysis of the 110 base pair minimal regulatory element suggests
that Wnt-1 regulation is complex, involving different regulatory interactions for
activation and the later maintenance of transgene expression in the dorsal
midbrain and ventral diencephalon, and at the midbrain-hindbrain junction.
PMID- 9636088
TI - faint sausage encodes a novel extracellular protein of the immunoglobulin
superfamily required for cell migration and the establishment of normal axonal
pathways in the Drosophila nervous system.
AB - We examined the structure of the nervous system in Drosophila embryos homozygous
for a null mutation in the faint sausage (fas) gene. In the peripheral nervous
system (PNS) of fas mutants, neurons fail to delaminate from the ectodermal
epithelium; in the central nervous system (CNS), the positions of neuronal cell
bodies and glial cells are abnormal and normal axonal pathways do not form.
Sequence analysis of fas cDNAs revealed that the fas protein product has
characteristics of an extracellular protein and that it is a novel member of the
immunoglobulin (Ig) superfamily. In situ hybridization demonstrated that fas
transcripts are expressed throughout the embryo but they are in relatively high
concentrations in the lateral ectoderm, from which the peripheral nervous system
delaminates and in the CNS. Antiserum directed against Fas protein was found to
stain neurons but not glia in the CNS. We conclude that fas encodes a protein
that, in the developing nervous system, is present on the surface of neurons and
is essential for nerve cell migration and the establishment of axonal pathways.
PMID- 9636089
TI - Phasic boosting of medial perforant path-evoked granule cell output time-locked
to spontaneous dentate EEG spikes in awake rats.
AB - Dentate spikes (DSs) are positive-going field potential transients that occur
intermittently in the hilar region of the dentate gyrus during alert wakefulness
and slow-wave sleep. The function of dentate spikes is unknown; they have been
suggested to be triggered by perforant path input and are associated with firing
of hilar interneurons and inhibition of CA3 pyramidal cells. Here we investigated
the effect of DSs on medial perforant path (MPP)-granule cell-evoked transmission
in freely moving rats. The MPP was stimulated selectively in the angular bundle
while evoked field potentials and the EEG were recorded with a vertical
multielectrode array in the dentate gyrus. DSs were identified readily on the
basis of their characteristic voltage-versus-depth profile, amplitude, duration,
and state dependency. Using on-line detection of the DS peak, the timing of MPP
stimulation relative to single DSs was controlled. DS-triggered evoked responses
were compared with conventional, manually evoked responses in still-alert
wakefulness (awake immobility) and, in some cases, slow-wave sleep. Input-output
curves were obtained with stimulation on the positive DS peak (0 delay) and at
delays of 50, 100, and 500 ms. Stimulation on the peak DS was associated with a
significant increase in the population spike amplitude, a reduction in population
spike latency, and a decrease in the field excitatory postsynaptic potential
(fEPSP) slope, relative to manual stimulation. Granule cell excitability was
enhanced markedly during DSs, as indicated by a mean 93% increase in the
population spike amplitude and a leftward shift in the fEPSP-spike relation.
Maximum effects occurred at the DS peak, and lasted between 50 and 100 ms. Paired
pulse inhibition of the population spike was unaffected, indicating intact
recurrent inhibition during DSs. The results demonstrate enhancement of perforant
path-evoked granule cell output time-locked to DSs. DSs therefore may function to
intermittently boost excitatory transmission in the entorhinal cortex-dentate
gyrus-CA3 circuit. Such a mechanism may be important in the natural induction of
long-term potentiation in the dentate gyrus and CA3 regions.
PMID- 9636090
TI - Pointing in 3D space to remembered targets. I. Kinesthetic versus visual target
presentation.
AB - This study investigated the influence of different modalities of target
information (visual, kinesthetic) on the accuracy, kinematics, and interjoint
coordination of pointing movements to remembered targets. The targets were
presented by a robot arm in five locations in three-dimensional (3D) space,
either as a point of light in a dark room ("visual" condition), or
kinesthetically. Relative pointing accuracy in the visual compared with
kinesthetic conditions was influenced by the target location: pointing errors
were the largest for the visual targets most eccentric relative to the subject's
head. In addition, for the two most lateral targets, the final arm positions
were, on average, closer to the center than the targets in the visual condition
and farther from the center than the targets in the kinesthetic conditions. This
result suggests that the pattern of errors in the visual condition described
elsewhere ("range effect") may derive from visual processing rather than motor
planning and implementation. Two modes of kinesthetic target presentation were
utilized. During "passive" kinesthetic presentation of the target, the
experimenter moved the subject's relaxed arm. Alternately, in "active"
kinesthetic presentation of the target, the subject actively (with minimal help
from the experimenter) moved his arm. No visual feedback was allowed in either
kinesthetic condition. The variability in the final fingertip position was
significantly smaller in the active condition than in the passive condition. In
contrast, variability in the final values of arm orientation angles did not
differ significantly in the active and passive conditions. This apparent
contradiction may be resolved by the fact that, for the given target location,
the influence of the deviation of these angles in the given trial from their
average values on the position of the fingertip tended to be mutually
compensated, and this tendency was stronger in the active condition. Our analysis
of the correlations among the arm orientation angles and of the relationship
between the initial and final arm configurations suggests that the kinesthetic
conditions enabled the implementation of a mixture of strategies for achieving
accuracy. The first strategy is to use a specific memory of an adequate arm
configuration (that assumed during target presentation), such that accuracy is
achieved by using this memory as a template. The second strategy is to use
synergistically coordinating joint angles, such that accuracy is achieved by
focusing on a specific endpoint that can be reached by a range of equivalent arm
positions. The latter strategy was better utilized in the active condition. In
conclusion, our results indicate that human subjects can use diverse sensory
information to achieve comparable final accuracy, but that the details of the
strategies employed differ with the kind of information available.
PMID- 9636091
TI - Ionic basis for serotonin-induced bistable membrane properties in guinea pig
trigeminal motoneurons.
AB - Intracellular recordings and pharmacological manipulations were employed to
investigate the ionic basis for serotonin-induced bistable membrane behaviors in
guinea pig trigeminal motoneurons (TMNs). In voltage clamp, 10 microM serotonin
(5-HT) induced a region of negative slope resistance (NSR) in the steady-state
current-voltage (I-V) relationship at potentials less negative than -58 mV,
creating the necessary conditions for membrane bistability. The contributions of
sustained Na+ and Ca2+ currents to the generation of the NSR were investigated
using specific ion channel antagonists and agonists. The NSR was eliminated by
the L-type Ca2+ channel antagonist nifedipine (5-10 microM), indicating the
contribution of L channels. In nifedipine, inward rectification was present in
the I-V relationship in a similar voltage range (greater than -58 mV). This
region was subsequently linearized by tetrodotoxin (TTX), indicating the presence
of a persistent Na+ current. When the 5-HT-induced NSR was eliminated by
perfusion in low Ca2+ solution (0.4 mM), it was restored by the Na+ channel
agonist veratridine (10 microM). Commensurate with bistability, in current clamp
during bath application of 5-HT, plateau potentials were elicited by transient
depolarizing or hyperpolarizing stimuli. Plateau potentials evoked by
depolarization were observed under control and TTX conditions, but were blocked
by nifedipine, suggesting the participation of an L-type Ca2+ current. Plateau
potentials initiated after release from hyperpolarization (anode break) were
blocked by 300 microM Ni2+, suggesting the responses relied on deinactivation of
a T-type Ca2+ current. Conditional bursting was also observed in 5-HT. Nifedipine
or low Ca2+ solutions blocked bursting, and the L-channel agonist Bay K 8644 (10
microM) extended the duration of individual bursts, demonstrating the role of L
type Ca2+ currents. Interestingly, when bursting was blocked by nifedipine or low
Ca2+, it could be restored by veratridine application via enhancement of the
persistent Na+ current. We conclude that bistable membrane behaviors in TMNs are
mediated by L-type Ca2+ and persistent Na+ currents. 5-HT is associated with
enhancement of TMN activity during oral-motor activity; the induction of bistable
membrane properties by 5-HT represents a cellular mechanism for this enhancement.
PMID- 9636092
TI - Spatiotemporal structure of cortical activity: properties and behavioral
relevance.
AB - The study was designed to reveal occurrences of precise firing sequences (PFSs)
in cortical activity and to test their behavioral relevance. Two monkeys were
trained to perform a delayed-response paradigm and to open puzzle boxes.
Extracellular activity was recorded from neurons in premotor and prefrontal areas
with an array of six microelectrodes. An algorithm was developed to detect PFSs,
defined as a set of three spikes and two intervals with a precision of +/-1 ms
repeating significantly more than expected by chance. The expected level of
repetition was computed based on the firing rate and the pairwise correlation of
the participating units, assuming a Poisson distribution of event counts.
Accordingly, the search for PFSs was corrected for rate modulations. PFSs were
found in 24/25 recording sessions. Most PFSs (76%) were composed of spikes of
more than one unit but usually not more than two units (67%). The PFSs spanned
hundreds of milliseconds, and the average interval between two events within the
PFSs was 200 ms. No traces of periodic oscillations were found in the PFS
intervals. The bins of the matrix that were defined as PFSs were isolated
temporally: the spikes that generated PFSs were not associated with high
frequency bursts or rapid coherent rate fluctuations. A given PFS tended to be
correlated with the animal's behavior. Furthermore, for 19% of the PFS pairs that
shared the same unit composition, each member of the pair was associated with a
different type of behavior. The PFSs often appeared in clusters that were
associated with particular phases of the behavior. The firing rate of single
units did not provide a full explanation for the timing and structure of these
clusters. A reduced spike train (RST) was defined for each unit by taking all
spikes of that unit that were part of any PFS. In 88% of the cases the degree of
modulation of the RST was higher than that of the complete spike train. The
results suggest that relevant information is carried by the fine temporal
structure of cortical activity. A coding scheme that involves such temporal
structures is rich and sufficiently flexible to facilitate a rapid organization
of cortical neurons into functional groups. The results can be accounted for by
the synfire chain model, which suggests that cortical activity is mediated by
synchronous activation of neural groups in a reverberatory mode.
PMID- 9636093
TI - Three-dimensional analysis of spontaneous and thalamically evoked gamma
oscillations in auditory cortex.
AB - The purpose of this study was to investigate interactions among laminar cell
populations producing spontaneous and evoked high-frequency (approximately 40 Hz)
gamma oscillations in auditory cortex. Electrocortical oscillations were recorded
using a 64-channel epipial electrode array and a 16-channel linear laminar
electrode array while electrical stimulation was delivered to the posterior
intralaminar (PIL) nucleus. Spontaneous gamma oscillations, and those evoked by
PIL stimulation, are confined to a location overlapping primary and secondary
auditory cortex. Current source-density and principal components analysis of
laminar recordings at this site indicate that the auditory evoked potential (AEP)
complex is characterized by a stereotyped asynchronous activation of supra- and
infragranular cell populations. Similar analysis of spontaneous and evoked gamma
waves reveals a close spatiotemporal similarity to the laminar AEP, indicating
rhythmic interactions between supra- and infragranular cell groups during these
oscillatory phenomena. We conclude that neural circuit interactions producing the
laminar AEP onset in auditory cortex are the same as those generating evoked and
spontaneous gamma oscillations.
PMID- 9636094
TI - Contribution of Ca2+-activated K+ channels to central chemosensitivity in
cultivated neurons of fetal rat medulla.
AB - Neurons in fetal rat medullary slices that exhibited spontaneous electrical
activity after blockade of synaptic transmission were investigated for their
response to decreases in extracellular pH. Increases in [H+] (induced either by
fixed acid or increases in PCO2) induced a significant increase in the frequency
of action potentials, associated with a membrane depolarization, and/or increases
in the slope of the interspike depolarization. In addition, CO2/H+ prolonged the
repolarizing phase of action potentials and reduced the afterhyperpolarization,
suggesting that K+ channels were the primary site of CO2/H+ action. The type of
K+ channel that was modulated by CO2/H+ was identified by application of agents
that inhibited Ca2+-activated K+ channels either directly (tetraethylammonium
chloride, TEA) or indirectly (Cd2+ ions) by inhibiting Ca2+ influx. CO2/H+
effects on neuronal activity were abolished after application of these blockers.
The contribution of Ca2+-activated K+ channels to H+ sensitivity of these neurons
was confirmed further in voltage-clamp experiments in which outward rectifying I
V curves were recorded that revealed a zero current potential of -70 mV. CO2/H+
induced a prominent reduction in outward currents and shifted the zero current
potential to more positive membrane potentials (mean -63 mV). The CO2/H+
sensitive current reversed at -72 mV and was blocked by external application of
TEA. It is concluded that CO2/H+ exerts its stimulatory effects on fetal
medullary neurons by inhibition of Ca2+-activated K+ channels, either directly or
indirectly, by blocking voltage-dependent Ca2+ channels, which in turn results in
a reduction of K+ efflux and in cell depolarization.
PMID- 9636095
TI - Properties of horizontal saccades accompanied by blinks.
AB - Using the magnetic search coil technique to record eye and lid movements, we
investigated the effect of voluntary blinks on horizontal saccades in five normal
human subjects. The main goal of the study was to determine whether changes in
the dynamics of saccades with blinks could be accounted for by a superposition of
the eye movements induced by blinks as subjects fixated a stationary target and
saccadic movements made without a blink. First, subjects made voluntary blinks as
they fixed on stationary targets located straight ahead or 20 degrees to the
right or left. They then made saccades between two continuously visible targets
20 or 40 degrees apart, while either attempting not to blink, or voluntarily
blinking, with each saccade. During fixation of a target located straight ahead,
blinks induced brief downward and nasalward deflections of eye position. When
subjects looked at targets located at right or left 20 degrees, similar initial
movements were made by four of the subjects, but the amplitude of the adducted
eye was reduced by 65% and was followed by a larger temporalward movement. Blinks
caused substantial changes in the dynamic properties of saccades. For 20 degrees
saccades made with blinks, peak velocity and peak acceleration were decreased by
approximately 20% in all subjects compared with saccades made without blinks.
Blinks caused the duration of 20 degrees saccades to increase, on average, by
36%. On the other hand, blinks had only small effects on the gain of saccades.
Blinks had little influence on the relative velocities of centrifugal versus
centripetal saccades, and abducting versus adducting saccades. Three of five
subjects showed a significantly increased incidence of dynamic overshoot in
saccades accompanied by blinks, especially for 20 degrees movements. Taken with
other evidence, this finding suggests that saccadic omnipause neurons are
inhibited by blinks, which have longer duration than the saccades that company
them. In conclusion, the changes in dynamic properties of saccades brought about
by blinks cannot be accounted for simply by a summation of gaze perturbations
produced by blinks during fixation and saccadic eye movements made without
blinks. Our findings, especially the appearance of dynamic overshoots, suggest
that blinks affect the central programming of saccades. These effects of blinks
need to be taken into account during studies of the dynamic properties of
saccades.
PMID- 9636096
TI - Differential regulation of synaptic inputs to dentate hilar border interneurons
by metabotropic glutamate receptors.
AB - Regulation of synaptic transmission by metabotropic glutamate receptors (mGluRs)
was examined at two excitatory inputs to interneurons with cell bodies at the
granule cell-hilus border in hippocampal slices taken from neonatal rats.
Subgroup-selective mGluR agonists altered the reliability, or probability of
transmitter release, of evoked minimal excitatory synaptic inputs and decreased
the amplitudes of excitatory postsynaptic currents (EPSCs) evoked with
conventional stimulation. The group II-selective agonist, (2S,1R',2R',3R')-2-(2,
3-dicarboxylcyclopropyl) glycine (DCG-IV; 1 microM), reversibly depressed the
reliability of EPSCs evoked by stimulation of the dentate granule cell layer.
However, DCG-IV had no significant effect on EPSCs evoked by CA3 stimulation in
the majority (82%) of hilar border interneurons. Both the group III-selective
agonist, -(+)-2-amino-4-phosphonobutyric acid (-AP4; 3 microM), and the group I
selective agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG; 20 microM) reversibly
depressed synaptic input to interneurons from both CA3 and the granule cell
layer. We conclude that multiple pharmacologically distinct mGluRs
presynaptically regulate synaptic transmission at two excitatory inputs to hilar
border interneurons. Further, the degree of mGluR-meditated depression of
excitatory drive is greater at synapses from dentate granule cells onto
interneurons than at synapses from CA3 pyramidal cells.
PMID- 9636097
TI - Effect of bicuculline on thalamic activity: a direct blockade of IAHP in
reticularis neurons.
AB - The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts
in the thalamus and thus plays an important role in regulating the excitability
of the thalamocortical network. Inhibition occurs through GABAergic synapses on
relay cells as well as through GABAergic synapses between reticularis neurons
themselves. Here we report that the role and mechanisms of this inhibition, which
frequently have been studied using N-methyl derivatives of the gamma-aminobutyric
acid-A (GABAA) receptor antagonist bicuculline, should be revisited. Using the
whole cell patch-clamp technique in thalamic slices from young rats, we observed
an enhancement by bicuculline methiodide, methobromide, and methochloride
(collectively referred to as bicuculline-M; 5-60 microM) of the low-threshold
calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin
(1 microM) and was not reproduced in picrotoxin (100-300 microM). The effect did
not involve activation of any GABA receptor subtype. Voltage-clamp recordings
showed that bicuculline-M blocked the current underlying the low-threshold spike
burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100
nM). Recordings from nucleated patches extracted from reticularis neurons
demonstrated that this effect was not mediated by modulation of the release of an
unidentified neurotransmitter but that bicuculline-M directly blocks small
conductance (SK) channels. The AHP-blocking effect also was observed in other
brain regions, demonstrating that although bicuculline-M is a potent GABAA
receptor antagonist, it is of limited value in assessing GABAergic network
interactions, which should be studied using picrotoxin or bicuculline-free base.
However, bicuculline-M may provide a useful tool for developing nonpeptide
antagonists of SK channels.
PMID- 9636098
TI - Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip
neurons during a spatial working memory task.
AB - Single-unit recording studies of posterior parietal neurons have indicated a
similarity of neuronal activation to that observed in the dorsolateral prefrontal
cortex in relation to performance of delayed saccade tasks. A key issue addressed
in the present study is whether the different classes of neuronal activity
observed in these tasks are encountered more frequently in one or the other area
or otherwise exhibit region-specific properties. The present study is the first
to directly compare these patterns of neuronal activity by alternately recording
from parietal area 7ip and prefrontal area 8a, under the identical behavioral
conditions, within the same hemisphere of two monkeys performing an oculomotor
delayed response task. The firing rate of 222 posterior parietal and 235
prefrontal neurons significantly changed during the cue, delay, and/or saccade
periods of the task. Neuronal responses in the two areas could be distinguished
only by subtle differences in their incidence and timing. Thus neurons responding
to the cue appeared earliest and were more frequent among the task-related
neurons within parietal cortex, whereas neurons exhibiting delay-period activity
accounted for a larger proportion of task-related neurons in prefrontal cortex.
Otherwise, the task-related neuronal activities were remarkably similar. Cue
period activity in prefrontal and parietal cortex exhibited comparable spatial
tuning and temporal duration characteristics, taking the form of phasic, tonic,
or combined phasic/tonic excitation in both cortical populations. Neurons in both
cortical areas exhibited sustained activity during the delay period with nearly
identical spatial tuning. The various patterns of delay-period activity-tonic,
increasing or decreasing, alone or in combination with greater activation during
cue and/or saccade periods-likewise were distributed to both cortical areas.
Finally, similarities in the two populations extended to the proportion and
spatial tuning of presaccadic and postsaccadic neuronal activity occurring in
relation to the memory-guided saccade. The present findings support and extend
evidence for a faithful duplication of receptive field properties and virtually
every other dimension of task-related activity observed when parietal and
prefrontal cortex are recruited to a common task. This striking similarity
attests to the principal that information shared by a prefrontal region and a
sensory association area with which it is connected is domain specific and not
subject to hierarchical elaboration, as is evident at earlier stages of
visuospatial processing.
PMID- 9636099
TI - Effects of intrathecal alpha1- and alpha2-noradrenergic agonists and
norepinephrine on locomotion in chronic spinal cats.
AB - Noradrenergic drugs, acting on alpha adrenoceptors, have been found to play an
important role in the initiation and modulation of locomotor pattern in adult
cats after spinal cord transection. There are at least two subtypes of alpha
adrenoceptors, alpha1 and alpha2 adrenoceptors. The aim of this study was to
investigate the effects of selective alpha1 and alpha2 agonists in the initiation
and modulation of locomotion in adult chronic cats in the early and late stages
after complete transection at T13. Five cats, chronically implanted with an
intrathecal cannula and electromyographic (EMG) electrodes were used in this
study. Noradrenergic drugs including alpha2 agonists (clonidine, tizanidine, and
oxymetazoline) and an antagonist, yohimbine, one alpha1 agonist (methoxamine),
and a blocker, prazosin, as well as norepinephrine were injected intrathecally.
EMG activity synchronized to video images of the hindlimbs were recorded before
and after each drug injection. The results show differential effects of alpha1
and alpha2 agonists in the initiation of locomotion in early spinal cats (i.e.,
in the first week or so when there is no spontaneous locomotion) and in the
modulation of locomotion and cutaneous reflexes in the late-spinal cats (i.e.,
when cats have recovered spontaneous locomotion). In early spinal cats, all three
alpha2 agonists were found to initiate locomotion, although their action had a
different time course. The alpha1 agonist methoxamine induced bouts of nice
locomotor activity in three spinal cats some hours after injection but only
induced sustained locomotion in one cat in which the effects were blocked by the
alpha1 antagonist prazosin. In late spinal cats, although alpha2 agonists
markedly increased the cycle duration and flexor muscle burst duration and
decreased the weight support or extensor activity (effects blocked by an alpha2
antagonist, yohimbine), alpha1 agonist increased the weight support and primarily
the extensor activity of the hindlimbs without markedly changing the timing of
the step cycle. Although alpha2 agonists, especially clonidine, markedly reduced
the cutaneous excitability and augmented the foot drag, the alpha1 agonist was
found to increase the cutaneous reflex excitability. This is in line with
previously reported differential effects of activation of the two receptors on
motoneuron excitability and reflex transmission. Noradrenaline, the
neurotransmitter itself, increased the cycle duration and at the same time
retained the cutaneous excitability, thus exerting both alpha1 and alpha2
effects. This work therefore suggests that different subclasses of noradrenergic
drugs could be used to more specifically target aspects of locomotor deficits in
patients after spinal injury or diseases.
PMID- 9636100
TI - Cooperative mechanisms between leg joints of Carausius morosus I. Nonspiking
interneurons that contribute to interjoint coordination.
AB - Three nonspiking interneurons are described in this paper that influence the
activity of the motor neurons of three muscles of the proximal leg joints of the
stick insect. Interneurons were recorded and stained intracellularly by glass
microelectrodes; motor neurons were recorded extracellularly with oil-hook
electrodes. The motor neurons innervate the two subcoxal muscles, the protractor
and retractor coxae, and the thoracic part of the depressor trochanteris muscle.
The latter spans the subcoxal joint before inserting the trochanter, thus
coupling the two proximal joints mechanically. The three interneurons are briefly
described here. First, interneuron NS 1 was known to become more excited during
the swing phase of the rear and the stance phase of the middle leg. When
depolarized it excited several motor neurons of the retractor coxae. This
investigation revealed that it inhibits the activity of protractor and thoracic
depressor motor neurons when depolarized as well. In a pilocarpine-activated
animal, the membrane potential showed oscillations in phase with the activity of
protractor motor neurons, suggesting that NS 1 might contribute to the transition
from swing to stance movement. Second, interneuron NS 2 inhibits motor neurons of
protractor and thoracic depressor when depolarized. In both a quiescent and a
pilocarpine-activated animal, hyperpolarizing stimuli excite motor neurons of
both muscles via disinhibition. In one active animal the disinhibiting stimuli
were sufficient to generate swing-like movements of the leg. In pilocarpine
activated preparations the membrane potential oscillated in correlation with the
motor neuronal activity of the protractor coxae and thoracic depressor muscle.
Hyperpolarizing stimuli induced or reinforced the protractor and thoracic
depressor bursts and inhibited the activity of the motor neurons of the retractor
coxae muscle, the antagonistic muscle of the protractor. Therefore interneuron NS
2 can be regarded as an important premotor interneuron for the switching from
stance to swing and from swing to stance. Finally, interneuron NS 3 inhibits the
spontaneously active motor neurons of both motor neuron pools in the quiescent
animal. During pilocarpine-induced protractor bursts, depolarizing stimuli
applied to the interneuron excited several protractor motor neurons with large
action potentials and one motor neuron of the thoracic depressor. No oscillations
of the membrane potentials were observed. Therefore this interneuron might
contribute to the generation of rapid leg movements. The results demonstrated
that the two proximal joints are coupled not only mechanically but also neurally
and that the thoracic part of the depressor appears to function as a part of the
swing-generating system.
PMID- 9636101
TI - Cooperative mechanisms between leg joints of Carausius morosus II. Motor neuron
activity and influence of conditional bursting interneuron.
AB - The activity of the motor neuron pools of the protractor coxae muscle and of the
thoracic part of the depressor trochanteris muscle during forward walking in the
stick insect was investigated, and a spiking local interneuron, able to produce
"endogenous bursting" and innervating both motor neuron pools, was identified.
Extracellular recordings of the motor neurons innervating the protractor and the
thoracic depressor of front, middle, and rear legs, respectively, were made with
oil-hook electrodes from the peripheral nerves nl2c and nl4a while the animals
were walking on a styrofoam treadwheel. The corresponding leg movements were
registered and phase histograms were created with the software Spike2.
Intracellular recordings were made in the neuropile of the metathoracic ganglion
with glass electrodes filled with the dye Lucifer yellow. In all three legs
measured (front, middle, and rear), both motor neuron pools increased their
activity during the swing movement. The increase in the activity of the
protractor motor neurons started at the end of the stance approximately 100 ms
before reaching the posterior extreme position (PEP), and the activity of the
large-sized depressor motor neurons increased as soon as the tarsus was lifted at
the PEP. A local spiking interneuron was identified that excited both motor
neuron pools. In 4 of 23 recordings the interneuron started to burst in synchrony
with protractor and thoracic depressor motor neurons. During bursting a
depolarizing stimulus reinforced and a hyperpolarizing stimulus inhibited the
activity of both motor neuron pools. Thus we conclude that the thoracic part of
the depressor trochanteris muscle might be a component of the neuromuscular
system that shapes the swing movement. The two proximal joints, subcoxal and coxa
trochanter, connected mechanically via the thoracic part of the depressor
trochanteris muscle, are also connected neurally by segmental and intersegmental
spiking interneurons (this paper) and by nonspiking local interneurons (see
companion paper).
PMID- 9636102
TI - AMPA and NMDA receptors expressed by differentiating Xenopus spinal neurons.
AB - N-methyl--aspartate (NMDA) receptors are often the first ionotropic glutamate
receptors expressed at early stages of development and appear to influence
neuronal differentiation by mediating Ca2+ influx. Although less well studied,
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors also
can generate Ca2+ elevations and may have developmental roles. We document the
presence of AMPA and NMDA class receptors and the absence of kainate class
receptors with whole cell voltage-clamp recordings from Xenopus embryonic spinal
neurons differentiated in vitro. Reversal potential measurements indicate that
AMPA receptors are permeable to Ca2+ both in differentiated neurons and at the
time they first are expressed. The PCa/Pmonocation of 1.9 is close to that of
cloned Ca2+-permeable AMPA receptors expressed in heterologous systems. Ca2+
imaging reveals that Ca2+ elevations are elicited by AMPA or NMDA in the absence
of Mg2+. The amplitudes and durations of these agonist-induced Ca2+ elevations
are similar to those of spontaneous Ca2+ transients known to act as
differentiation signals in these cells. Two sources of Ca2+ amplify AMPA- and
NMDA-induced Ca2+ elevations. Activation of voltage-gated Ca2+ channels by AMPA-
or NMDA-mediated depolarization contributes approximately 15 or 30% of cytosolic
Ca2+ elevations, respectively. Activation of either class of receptor produces
elevations of Ca2+ that elicit further release of Ca2+ from thapsigargin
sensitive but ryanodine-insensitive stores, contributing an additional
approximately 30% of Ca2+ elevations. Voltage-clamp recordings and Ca2+ imaging
both show that these spinal neurons express functional AMPA receptors soon after
neurite initiation and before expression of NMDA receptors. The Ca2+ permeability
of AMPA receptors, their ability to generate significant elevations of [Ca2+]i,
and their appearance before synapse formation position them to play roles in
neural development. Spontaneous release of agonists from growth cones is detected
with glutamate receptors in outside-out patches, suggesting that spinal neurons
are early, nonsynaptic sources of glutamate that can influence neuronal
differentiation in vivo.
PMID- 9636103
TI - Changes in quantal size distributions upon experimental variations in the
probability of release at striatal inhibitory synapses.
AB - Postsynaptic inhibitory gamma-aminobutyric acid-A (GABAA)-receptor-mediated
current responses were measured using simultaneous pre- and postsynaptic whole
cell recordings in primary cell cultures of rat striatum. Substitution of Sr2+
for extracellular Ca2+ strongly desynchronized the inhibitory postsynaptic
currents (IPSCs), resulting in a succession of asynchronous IPSCs (asIPSCs). The
rise times and decay time constants of individual evoked asIPSCs were not
significantly different from those of miniature IPSCs that are the result of
spontaneous vesicular release of GABA. Thus asIPSCs reflect quantal transmission
at the individual contacts made by one presynaptic neuron on the recorded
postsynaptic cell. Increasing the concentration of Sr2+ from 2 to 10 mM and
decreasing that of Mg2+ from 5 to 1 mM produced an increase in the frequency of
asIPSCs consistent with an enhancement of the mean probability of release (Pr).
At the same time the amplitude distribution of asIPSCs was shifted toward larger
values, whereas responses to exogenously applied GABA on average were slightly
decreased in amplitude. Application of the GABAB-receptor agonist baclofen (3-10
microM) strongly reduced the frequency of asIPSC, consistent with a decrease in
Pr, and led to a shift of the amplitude distribution toward smaller values.
Baclofen had no effect on responses to exogenously applied GABA. In summary, our
data suggest that at striatal inhibitory connections the weight of single
contacts may be controlled presynaptically by variation in the amount of
transmitter released.
PMID- 9636104
TI - Calcium-sensitive calcium influx in photoreceptor inner segments.
AB - The effect of external calcium concentration ([Ca2+]o) on membrane potential
dependent calcium signals in isolated tiger salamander rod and cone photoreceptor
inner segments was investigated with patch-clamp and calcium imaging techniques.
Mild depolarizations led to increases in intracellular Ca2+ levels ([Ca2+]i) that
were smaller when [Ca2+]o was elevated to 10 mM than when it was 3 mM, even
though maximum Ca2+ conductance increased 30% with the increase in [Ca2+]o. When
external calcium was lowered to 1 mM [Ca2+]o, maximum Ca2+ conductance was
reduced, as expected, but the mild depolarization-induced increase in [Ca2+]i was
larger than in 3 mM [Ca2+]o. In contrast, when photoreceptors were strongly
depolarized, the increase in [Ca2+]i was less when [Ca2+]o was reduced. An
explanation for these observations comes from an assessment of Ca2+ channel
gating in voltage-clamped photoreceptors under changing conditions of [Ca2+]o.
Although Ca2+ conductance increased with increasing [Ca2+]o, surface charge
effects dictated large shifts in the voltage dependence of Ca2+ channel gating.
Relative to the control condition (3 mM [Ca2+]o), 10 mM [Ca2+]o shifted Ca2+
channel activation 8 mV positive, reducing channel open probability over a broad
range of potentials. Reducing [Ca2+]o to 1 mM reduced Ca2+ conductance but
shifted Ca2+ channel activation negative by 6 mV. Thus the intracellular calcium
signals reflect a balance between competing changes in gating and permeation of
Ca2+ channels mediated by [Ca2+]o. In mildly depolarized cells, the [Ca2+]o
induced changes in Ca2+ channel activation proved stronger than the [Ca2+]o
induced changes in conductance. In response to the larger depolarizations caused
by 80 mM [K+]o, the opposite is true, with conductance changes dominating the
effects on channel activation.
PMID- 9636105
TI - Ictal epileptiform activity in the CA3 region of hippocampal slices produced by
pilocarpine.
AB - Pilocarpine, a muscarinic agonist, produces status epilepticus that is associated
with the later development of chronic recurrent seizures. When applied to rat
hippocampal slices, pilocarpine (10 microM) produced brief (<200 ms) epileptiform
discharges that resembled interictal activity that occurs between seizures, as
well as more prolonged synchronous neuronal activation that lasted seconds (3-20
s), and was comparable to ictal or seizures-like discharges. We assessed the
factors that favored ictal patterns of activity and determined the biophysical
properties of the ictal discharge. The probability of observing ictal discharges
was increased when extracellular potassium ([K+]o) was increased from 5 to 7.5
mM. Raising [K+]o to 10 mM resulted in loss of ictal patterns and, in 20 of 34
slices, desynchronization of epileptiform activity. Making the artificial
cerebrospinal fluid (ACSF) hyposmotic favored ictal discharges at 5 mM [K+]o, but
shifted 7.5 mM [K+]o ACSF patterns to interictal discharges or desynchronized
activity. Conversely, increasing osmolality suppressed ictal patterns. The
pilocarpine-induced ictal discharges were blocked by atropine (1 microM, n = 5),
a muscarinic antagonist, and pirenzepine (1 microM, n = 6), a selective M1
receptor antagonist. Kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic
acid receptor blockade stopped all epileptiform activity (n = 8). The N-methyl-
aspartate antagonist ,-2-amino-5-phosphonovaleric acid (100 microM, n = 34) did
not change the pattern of epileptiform activity but significantly increased the
rate of interictal discharges and prolonged the duration of ictal discharges. The
ictal discharge was characterized intracellularly by a depolarization that was
associated with action potential generation and persisted as a membrane
oscillation of 4-10 Hz. The ictal oscillations reversed in polarity at -22.7 +/-
2.2 mV (n = 11) with current-clamp recordings and -20.9 +/- 3.1 mV (n = 7) with
voltage-clamp recordings. The reversal potential of the ictal discharge in the
presence of the gamma-aminobutyric acid-A blocker bicuculline (10 microM, n = 6)
was -2.2 +/- 2.6 mV and was significantly different from that measured without
bicuculline. Bicuculline added to 7.5 mM [K+]o and 10 microM pilocarpine did not
cause epileptiform activity to change pattern but significantly increased the
rate of interictal discharges and prolonged the ictal discharge duration. Both
synaptic and nonsynaptic mechanisms are important for the generation of ictal
patterns of epileptiform activity. Although the synchronous epileptiform activity
produced by pilocarpine required fast glutamate-mediated synaptic transmission,
the transition from an interictal to ictal pattern of activity depended on [K+]o
and could be influenced by extracellular space.
PMID- 9636106
TI - Neurophysiological correlates of unconditioned and conditioned feeding behavior
in the pond snail Lymnaea stagnalis.
AB - We used a behavioral appetitive learning paradigm followed by
electrophysiological analysis to investigate the neuronal expression of
appetitive conditioning in Lymnaea. We first established the levels of
unconditioned and conditioned feeding responses in intact animals. We then
demonstrated that neuronal correlates of both unconditioned responses to touch
and food and a conditioned response to touch could be found in semi-intact
preparations of the same animals that had been subjected to behavioral tests and
conditioning trials. In the conditioning experiments, the experimental animals
received 15 trials in which touch to the lips, the conditioned stimulus (CS), was
paired with sucrose, the unconditioned food stimulus (US). Control animals
received 15 presentations of either CS or US, or both, applied in a random
manner. After training, a strong conditioned response to touch was established in
the experimental but not in the control groups. For subsequent
electrophysiological analysis of posttraining neuronal responses to the touch CS,
semi-intact preparations were set up from the same animals that had been
behaviorally conditioned or subjected to control procedures. Intracellular
recordings, made from previously identified motoneurons of the feeding system,
allowed the fictive feeding response to the CS to be monitored. In experimental
preparations, touch applied to the lips evoked significantly more fictive feeding
cycles than in controls, and this demonstrated the existence of a
neurophysiological correlate of the appetitively conditioned response observed in
the whole animals.
PMID- 9636107
TI - Functional specialization in auditory cortex: responses to frequency-modulated
stimuli in the cat's posterior auditory field.
AB - The mammalian auditory cortex contains multiple fields but their functional role
is poorly understood. Here we examine the responses of single neurons in the
posterior auditory field (P) of barbiturate- and ketamine-anesthetized cats to
frequency-modulated (FM) sweeps. FM sweeps traversed the excitatory response area
of the neuron under study, and FM direction and the linear rate of change of
frequency (RCF) were varied systematically. In some neurons, sweeps of different
sound pressure levels (SPLs) also were tested. The response magnitude (number of
spikes corrected for spontaneous activity) of nearly all field P neurons varied
with RCF. RCF response functions displayed a variety of shapes, but most
functions were of low-pass characteristic or peaked at rather low RCFs (<100
kHz/s). Neurons with strong responses to high RCFs (high-pass or nonselective RCF
response function characteristics) all displayed spike count-SPL functions to
tone burst onsets that were monotonic or weakly nonmonotonic. RCF response
functions and best RCFs often changed with SPL. For most neurons, FM directional
sensitivity, quantified by a directional sensitivity (DS) index, also varied with
RCF and SPL, but the mean and width of the distribution of DS indices across all
neurons was independent of RCF. Analysis of response timing revealed that the
phasic response of a neuron is triggered when the instantaneous frequency of the
sweep reaches a particular value, the effective Fi. For a given neuron, values of
effective Fi were independent of RCF, but depended on FM direction and SPL and
were associated closely with the boundaries of the neuron's frequency versus
amplitude response area. The standard deviation (SD) of the latency of the first
spike of the response decreased with RCF. When SD was expressed relative to the
rate of change of stimulus frequency, the resulting index of frequency jitter
increased with RCF and did so rather uniformly in all neurons and largely
independent of SPL. These properties suggest that many FM parameters are
represented by, and may be encoded in, orderly temporal patterns across different
neurons in addition to the strength of responses. When compared with neurons in
primary and anterior auditory fields, field P neurons respond better to
relatively slow FMs. Together with previous studies of responses to modulations
of amplitude, such as tone onsets, our findings suggest more generally that field
P may be best suited for processing signals that vary relatively slowly over
time.
PMID- 9636108
TI - Brain stem omnipause neurons and the control of combined eye-head gaze saccades
in the alert cat.
AB - When the head is unrestrained, rapid displacements of the visual axis-gaze shifts
(eye-re-space)-are made by coordinated movements of the eyes (eye-re-head) and
head (head-re-space). To address the problem of the neural control of gaze
shifts, we studied and contrasted the discharges of omnipause neurons (OPNs)
during a variety of combined eye-head gaze shifts and head-fixed eye saccades
executed by alert cats. OPNs discharged tonically during intersaccadic intervals
and at a reduced level during slow perisaccadic gaze movements sometimes
accompanying saccades. Their activity ceased for the duration of the saccadic
gaze shifts the animal executed, either by head-fixed eye saccades alone or by
combined eye-head movements. This was true for all types of gaze shifts studied:
active movements to visual targets; passive movements induced by whole-body
rotation or by head rotation about stationary body; and electrically evoked
movements by stimulation of the caudal part of the superior colliculus (SC), a
central structure for gaze control. For combined eye-head gaze shifts, the OPN
pause was therefore not correlated to the eye-in-head trajectory. For instance,
in active gaze movements, the end of the pause was better correlated with the
gaze end than with either the eye saccade end or the time of eye counterrotation.
The hypothesis that cat OPNs participate in controlling gaze shifts is supported
by these results, and also by the observation that the movements of both the eyes
and the head were transiently interrupted by stimulation of OPNs during gaze
shifts. However, we found that the OPN pause could be dissociated from the gaze
motor-error signal producing the gaze shift. First, OPNs resumed discharging when
perturbation of head motion briefly interrupted a gaze shift before its intended
amplitude was attained. Second, stimulation of caudal SC sites in head-free cat
elicited large head-free gaze shifts consistent with the creation of a large gaze
motor-error signal. However, stimulation of the same sites in head-fixed cat
produced small "goal-directed" eye saccades, and OPNs paused only for the
duration of the latter; neither a pause nor an eye movement occurred when the
same stimulation was applied with the eyes at the goal location. We conclude that
OPNs can be controlled by neither a simple eye control system nor an absolute
gaze control system. Our data cannot be accounted for by existing models
describing the control of combined eye-head gaze shifts and therefore put new
constraints on future models, which will have to incorporate all the various
signals that act synergistically to control gaze shifts.
PMID- 9636109
TI - Single olivocochlear neurons in the guinea pig. I. Binaural facilitation of
responses to high-level noise.
AB - Single medial olivocochlear (MOC) neurons were recorded from the cochlea of the
anesthetized guinea pig. We used tones and noise presented monaurally and
binaurally and measured responses for sounds up to 105 dB sound pressure level
(SPL). For monaural sound, MOC neuron firing rates were usually higher for noise
bursts than tone bursts, a situation not observed for afferent fibers of the
auditory nerve that were sampled in the same preparations. MOC neurons also
differed from afferent fibers in having less saturation of response. Some MOC
neurons had responses that continued to increase even at high sound levels.
Differences between MOC and afferent responses suggest that there is convergence
in the pathway to olivocochlear neurons, possibly a combination of inputs that
are at the characteristic frequency (CF) with others that are off the CF.
Opposite-ear noise almost always facilitated the responses of MOC neurons to
sounds in the main ear, the ear that best drives the unit. This binaural
facilitation depends on several characteristics that pertain to the main ear: it
is higher in neurons having a contralateral main ear (contra units), it is higher
at main-ear sound levels that are moderate (approximately 65 dB SPL), and it is
higher in neurons with low discharge rates to main-ear stimuli. Facilitation also
depends on parameters of the opposite-ear sound: facilitation increases with
noise level in the opposite ear until saturating, is greater for continuous noise
than noise bursts, and is usually greater for noise than for tones. Using optimal
opposite-ear facilitators and high-level stimuli, the firing rates of
olivocochlear neurons range up to 140 spikes/s, whereas for moderate-level
monaural stimuli the rates are <80 spikes/s. At high sound levels, firing rates
of olivocochlear neurons increase with CF, an increase that may compensate for
the known lower effectiveness of olivocochlear synapses on outer hair cells
responding to high frequencies. Overall, our results demonstrate a high MOC
response for binaural noise and suggest a prominent role for the MOC system in
environments containing binaural noise of high level.
PMID- 9636110
TI - Single olivocochlear neurons in the guinea pig. II. Response plasticity due to
noise conditioning.
AB - Previous studies have shown that daily, moderate-level sound exposure, or
conditioning, can reduce injury from a subsequent high-level noise exposure. We
tested the hypothesis that this conditioning produces an increased activity in
the olivocochlear efferent reflex, a reflex known to provide protection to the
cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2-4
kHz noise at 85 dB sound pressure level. This conditioning is known to reduce
damage from a subsequent high-level exposure to the same noise band. Responses to
monaural and binaural sound were recorded from single medial olivocochlear (MOC)
efferent neurons, and data from conditioned animals were compared with those
obtained from unexposed controls. MOC neurons were classified by their response
to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra
units, or either-ear units. There were no significant differences in the
distributions of these unit types between control and conditioned animals. There
were also no differences in other responses to monaural stimuli, including the
distribution of characteristic frequencies (CFs), the sharpness of tuning, or
thresholds at the CF. For binaural sound at high levels, particularly relevant to
sound-evoked activation of the MOC reflex during acoustic overstimulation, the
firing rates of MOC neurons with CFs just above the conditioning band showed
slight (but statistically significant) elevations relative to control animals.
Frequency regions just above the conditioning band also demonstrated maximum
conditioning-related protection; thus protection could be due, in part, to long
term changes in MOC discharge rates. For binaural sound at low levels, MOC firing
rates in conditioned animals also were increased significantly relative to
controls. Again, increases were largest for neurons with CFs just above the
conditioning band. For equivalent monaural sound, rates were not significantly
increased; thus, conditioning appears to increase binaural facilitation by
opposite-ear sound. These data indicate that MOC neurons show long-term
plasticity in acoustic responsiveness that is dependent on their acoustic
history.
PMID- 9636111
TI - Single-neuron modeling of LSO unit responses.
AB - We investigated, using a computational model, the biophysical correlates of
measured discharge patterns of lateral superior olive (LSO) neuron responses to
monaural and binaural stimuli. The model's geometry was based on morphological
data, and static electric properties of the model agree with available
intracellular responses to hyperpolarizing current pulses. Inhibitory synapses
were located on the soma and excitatory ones on the dendrites, which were modeled
as passive cables. The active properties of the model were adjusted to agree with
statistical measures derived from extracellular recordings. Calcium-dependent
potassium channels supplemented the usual Hodgkin-Huxley characterization for the
soma to produce observed serial interspike interval dependence characteristics.
Intracellular calcium concentration is controlled by voltage- and calcium
dependent potassium channels and by calcium diffusion and homeostatic mechanisms.
By adjusting the density of the calcium-dependent potassium channels, we could
span the observed range of transient response patterns found in different LSO
neurons. Inputs from the two ears were modeled as Poisson processes to describe
the responses to tone-burst stimuli. Transient and sustained responses to
monaural and binaural tone-burst stimuli over a wide range of stimulus conditions
could be well described by varying only the model's inputs. As found in
recordings, model responses having similar discharge rates but different binaural
stimulus combinations exhibited differences in interval statistics.
PMID- 9636112
TI - Voltage-clamp analysis and computer simulation of a novel cesium-resistant A
current in guinea pig laterodorsal tegmental neurons.
AB - Increased firing of cholinergic neurons of the laterodorsal tegmental nucleus
(LDT) plays a critical role in generating the behavioral states of arousal and
rapid eye movement sleep. The majority of these neurons exhibit a prominent
transient potassium current (IA) that shapes firing but the properties of which
have not been examined in detail. Although IA has been reported to be blocked by
intracellular cesium, the IA in LDT neurons appeared resistant to intracellular
cesium. The present study compared the properties of this cesium-resistant
current to those typically ascribed to IA. Whole cell recordings were obtained
from LDT neurons (n = 67) in brain slices with potassium- or cesium-containing
pipette solutions. A transient current was observed in cells dialyzed with each
solution (KGluc-85%; CsGluc-79%). However, in cesium-dialyzed neurons, the
transient current was inward at test potentials negative to about -35 mV.
Extracellular 4-aminopyridine (4-AP; 2-5 mM) blocked both inward and outward
current, suggesting the inward current was reversed IA rather than an unmasked
transient calcium current as previously suggested. This conclusion was supported
by increasing [K]o from 5 to 15 mM, which shifted the reversal potential
positively for both inward and outward current (+17.89 +/- 0.41 mV; mean +/- SE).
Moreover, recovery from inactivation was rapid (tau = 15.5 +/- 4 ms; n = 4), as
reported for IA, and both inward and outward transient current persisted in
calcium-free solution [0 calcium/4 mM ethylene glycol-bis(beta-aminoethyl ether)
N,N,N', N'-tetraacetic acid; n = 4] and during cadmium-blockade of calcium
currents (n = 3). Finally, the transient current was blocked by intracellular 4
AP indicating that adequate dialysis occurred during the recordings. Thus the Cs
resistant current is a subthreshold IA. We also estimated the voltage-dependence
of activation (V1/2 = -45.8 +/- 2 mV, k = 5.21 +/- 0.62 mV, n = 6) and
inactivation (V1/2 = -59. 0 +/- 2.38 mV, k = -5.4 +/- 0.49 mV, n = 3) of this
current. Computer simulations using a morphologically accurate model cell
indicated that except for the extreme case of only distal A-channels and a high
intracellular resistivity, our parameter estimates were good approximations. In
conclusion, guinea pig LDT neurons express subthreshold A-channels that are
resistant to intracellular cesium ions. This suggests that these channels differ
fundamentally in their ion permeation mechanism from those previously studied. It
remains to be determined if Cs+ resistance is common among brain A-channels or if
this property is conferred by known A-channel subunits.
PMID- 9636113
TI - Anatomy and physiology of principal cells of the medial nucleus of the trapezoid
body (MNTB) of the cat.
AB - We have recorded from principal cells of the medial nucleus of the trapezoid body
(MNTB) in the cat's superior olivary complex using either glass micropipettes
filled with Neurobiotin or horseradish peroxidase for intracellular recording and
subsequent labeling or extracellular metal microelectrodes relying on
prepotentials and electrode location. Labeled principal cells had cell bodies
that usually gave rise to one or two primary dendrites, which branched profusely
in the vicinity of the cell. At the electron microscopic (EM) level, there was a
dense synaptic terminal distribution on the cell body and proximal dendrites. Up
to half the measured cell surface could be covered with excitatory terminals,
whereas inhibitory terminals consistently covered about one-fifth. The distal
dendrites were very sparsely innervated. The thick myelinated axon originated
from the cell body and innervated nuclei exclusively in the ipsilateral auditory
brain stem. These include the lateral superior olive (LSO), ventral nucleus of
the lateral lemniscus, medial superior olive, dorsomedial and ventromedial
periolivary nuclei, and the MNTB itself. At the EM level the myelinated
collaterals gave rise to terminals that contained nonround vesicles and, in the
LSO, were seen terminating on cell bodies and primary dendrites. Responses of
MNTB cells were similar to their primary excitatory input, the globular bushy
cell (GBC), in a number of ways. The spontaneous spike rate of MNTB cells with
low characteristic frequencies (CFs) was low, whereas it tended to be higher for
higher CF units. In response to short tones, a low frequency MNTB cell showed
enhanced phase-locking abilities, relative to auditory nerve fibers. For cells
with CFs >1 kHz, the short tone response often resembled the primary-like with
notch response seen in many globular bushy cells, with a well-timed onset
component. Exceptions to and variations of this standard response were also
noted. When compared with GBCs with comparable CFs, the latency of the MNTB cell
response was delayed slightly, as would be expected given the synapse interposed
between the two cell types. Our data thus confirm that, in the cat, the MNTB
receives and converts synaptic inputs from globular bushy cells into a reasonably
accurate reproduction of the bushy cell spike response. This MNTB cell output
then becomes an important inhibitory input to a number of ipsilateral auditory
brain stem nuclei.
PMID- 9636114
TI - A role for the dorsal column in nociceptive visceral input into the thalamus of
primates.
AB - A possible role of the dorsal column (DC) in the processing of visceral pain has
gained attention after studies in the rat have revealed that the DC transmits a
major part of the pelvic visceral nociceptive input from the colon into the
thalamus. Furthermore, clinical interventions aimed at interrupting ascending DC
axons near the midline were successful in relieving the pain suffered by patients
with cancer of the pelvic organs. The purpose of this study was to check whether
a DC lesion in monkeys would reduce the responses of thalamic neurons to graded
colorectal distension (CRD) as in rats. Experiments were done on anesthetized
male monkeys (Macaca fascicularis). Extracellular single cell recordings were
made in the ventrolateral complex of the thalamus, mainly the ventral
posterolateral (VPL) nucleus, in response to visceral and cutaneous stimulation.
Of 80 VPL cells isolated, CRD activated 25, inhibited 25, and had no effect on 30
neurons. The responses of six viscerosensitive VPL neurons were recorded before
and after a lesion of the DC at or above the T10 spinal segment. Lesions of other
spinal tracts were made after the DC lesion. The results show that the DC lesion
significantly reduced the responses of the thalamic neurons tested with CRD by
>50%. Lesions of other tracts did not have a consistent effect. These results
corroborate findings in the rat and support the proposal that the DC plays an
important role in transmitting nociceptive visceral input into the thalamus and
subsequently in visceral pain.
PMID- 9636115
TI - Synaptically evoked glutamate transport currents may be used to detect the
expression of long-term potentiation in cerebellar culture.
AB - Cerebellar long-term potentiation (LTP) is a use-dependent increase in the
strength of the granule cell-Purkinje neuron synapse that occurs after brief
stimulation of granule cell axons at 2-8 Hz. Previous work has shown that
cerebellar LTP also may be seen when synaptic currents are evoked in granule cell
glial cell pairs in culture. This finding suggests a model in which cerebellar
LTP is expressed presynaptically and therefore may be detected by either neuronal
or glial postsynaptic cells. However, synaptic currents evoked in both granule
cell-glial cell pairs and granule cell-Purkinje neuron pairs in culture are
mediated primarily by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
(AMPA)/kainate receptors, raising the possibility that cerebellar LTP might be
expressed postsynaptically in both glial cells and Purkinje neurons in a similar
manner. To address this question, glutamate transport currents were recorded in
granule cell-glial cell pairs in culture by pharmacological isolation. These
currents were increased by substitution of internal Cl with NO3 and were blocked
by -pyrrolidine-2,4-dicarboxylate, both characteristics of the major cloned
Bergmann glial cell glutamate transporter, EAAT1. After acquisition of baseline
responses, LTP of isolated transport current was evoked by stimulation at 4 Hz
(100 pulses) and could be blocked by removal of external Ca during this
stimulation. The expression of LTP was associated with a decrease in the rate of
synaptic failures and a decrease in the degree of paired-pulse facilitation.
These findings, when taken together with the previous observation that both
Purkinje neuron and glial AMPA/kainate responses can be used to detect cerebellar
LTP, strongly suggest that the expression of cerebellar LTP is, at least in part,
presynaptic. This strategy should also be useful in illuminating the locus of
expression of other model systems of information storage such as hippocampal
LTP/long-term depression.
PMID- 9636116
TI - Different combinations of GABAA and GABAC receptors confer distinct temporal
properties to retinal synaptic responses.
AB - This study addresses how gamma-aminobutyric acid-A(GABAA) and GABAC receptors
confer distinct temporal properties to neuronal synaptic responses. The retina is
a model system for the study of postsynaptic contributions to synaptic responses
because GABAergic amacrine cells synapse onto neurons, which have different
combinations of GABAA and GABAC receptors. It is not known, however, how GABAA
versus GABAC receptors influence the time course of retinal synaptic responses or
what proportion of inhibitory input is mediated by each receptor type. We
examined the time courses of synaptic responses mediated by GABA receptors in
ganglion and bipolar cells by recording currents evoked by activating amacrine
cells with a stimulating electrode in the salamander retinal slice. The
pharmacologically isolated, GABAergic synaptic currents were long-lasting in
bipolar cells and relatively brief in ganglion cells. The receptors that mediated
these temporally distinct synaptic responses exhibited different pharmacological
properties. In ganglion cells, GABAergic synaptic currents were abolished by the
GABAA receptor antagonists bicuculline or SR95531. In bipolar cells, the GABAC
receptor antagonist 3-aminopropyl[methyl]phosphonic acid (3-APMPA) largely
blocked GABAergic synaptic responses; the remaining response was blocked by
bicuculline or SR95531. The GABAA receptor component of the bipolar cell response
was relatively brief compared with the GABAC receptor component. Puffing GABA
onto ganglion cell dendrites or bipolar cell terminals yielded similar
pharmacological and kinetic results, indicating that transmitter release
differences did not determine the response time courses. Moreover, the GABAC
receptors on bipolar cells may be different from those reported in rat or fish
retina because imidazole-4-acetic acid (I4AA), which acts as an antagonist in
these preparations, acts as an agonist in salamander. Our data show that the
prolonged synaptic responses in bipolar cells were mediated predominantly by
GABAC receptors, whereas transient synaptic responses in ganglion cells were
mediated by GABAA receptors.
PMID- 9636117
TI - Model of cortical-basal ganglionic processing: encoding the serial order of
sensory events.
AB - Several lines of evidence suggest that the prefrontal (PF) cortex and basal
ganglia are important in cognitive aspects of serial order in behavior. We
present a modular neural network model of these areas that encodes the serial
order of events into spatial patterns of PF activity. The model is based on the
topographically specific circuits linking the PF with the basal ganglia. Each
module traces a pathway from the PF, through the basal ganglia and thalamus, and
back to the PF. The complete model consists of an array of modules interacting
through recurrent corticostriatal projections and collateral inhibition between
striatal spiny units. The model's architecture positions spiny units for the
classification of cortical contexts and events and provides bistable cortical
thalamic loops for sustaining a representation of these contextual events in
working memory activations. The model was tested with a simulated version of a
delayed-sequencing task. In single-unit studies, the task begins with the
presentation of a sequence of target lights. After a short delay, the monkey must
touch the targets in the order in which they were presented. When instantiated
with randomly distributed corticostriatal weights, the model produces different
patterns of PF activation in response to different target sequences. These
patterns represent an unambiguous and spatially distributed encoding of the
sequence. Parameter studies of these random networks were used to compare the
computational consequences of collateral and feed-forward inhibition within the
striatum. In addition, we studied the receptive fields of 20,640 model units and
uncovered an interesting set of cue-, rank- and sequence-related responses that
qualitatively resemble responses reported in single unit studies of the PF. The
majority of units respond to more than one sequence of stimuli. A method for
analyzing serial receptive fields is presented and utilized for comparing the
model units to single-unit data.
PMID- 9636118
TI - Inhibitory glutamate receptor channels in cultured lobster stomatogastric
neurons.
AB - Inhibitory glutamate receptor channels (IGluRs) are ligand-gated ionotropic
receptors related to ionotropic gamma-aminobutyric acid (GABA) and glycine
receptors and expressed in neural and muscular tissues. In the crustacean
stomatogastric ganglion (STG), IGluRs mediate recurrent synaptic inhibition
central to the rhythmogenic capabilities of its embedded neural circuits. IGluRs
expressed in cultured spiny lobster STG neurons exhibited an EC50 of 1.2 mM and a
Hill coefficient of 1.4. They were neither cross-activated nor cross-desensitized
by GABA, although a distinct GABA-gated chloride current was observed. Glycine
did not evoke any current from STG neurons. The IGluR was weakly blocked by the
chloride channel blocker furosemide and the excitatory glutamate receptor
antagonist6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but was not inhibited by
bicuculline methiodide, strychnine, kynurenic acid, gamma--glutamylglycine, or
aspartate. Outside-out patch-clamp recordings were analyzed using the mean
variance histogram technique. Under excised-patch conditions, the receptor
exhibited only a single open state with an estimated unitary conductance of 80 +/
8. 6 (SD) pS. The distinct GABA receptor also displayed a single open state with
a conductance of 72 +/- 10 pS.
PMID- 9636119
TI - Commutative saccadic generator is sufficient to control a 3-D ocular plant with
pulleys.
AB - One-dimensional models of oculomotor control rely on the fact that, when
rotations around only one axis are considered, angular velocity is the derivative
of orientation. However, when rotations around arbitrary axes [3-dimensional (3
D) rotations] are considered, this property does not hold, because 3-D rotations
are noncommutative. The noncommutativity of rotations has prompted a long debate
over whether or not the oculomotor system has to account for this property of
rotations by employing noncommutative operators. Recently, Raphan presented a
model of the ocular plant that incorporates the orbital pulleys discovered, and
qualitatively modeled, by Miller and colleagues. Using one simulation, Raphan
showed that the pulley model could produce realistic saccades even when the
neural controller is commutative. However, no proof was offered that the good
behavior of the Raphan-Miller pulley model holds for saccades different from
those simulated. We demonstrate mathematically that the Raphan-Miller pulley
model always produces movements that have an accurate dynamic behavior. This is
possible because, if the pulleys are properly placed, the oculomotor plant
(extraocular muscles, orbital pulleys, and eyeball) in a sense appears
commutative to the neural controller. We demonstrate this finding by studying the
effect that the pulleys have on the different components of the innervation
signal provided by the brain to the extraocular muscles. Because the pulleys make
the axes of action of the extraocular muscles dependent on eye orientation, the
effect of the innervation signals varies correspondingly as a function of eye
orientation. In particular, the Pulse of innervation, which in classical models
of the saccadic system encoded eye velocity, here encodes a different signal,
which is very close to the derivative of eye orientation. In contrast, the Step
of innervation always encodes orientation, whether or not the plant contains
pulleys. Thus the Step can be produced by simply integrating the Pulse.
Particular care will be given to describing how the pulleys can have this
differential effect on the Pulse and the Step. We will show that, if orbital
pulleys are properly located, the neural control of saccades can be greatly
simplified. Furthermore, the neural implementation of Listing's Law is
simplified: eye orientation will lie in Listing's Plane as long as the Pulse is
generated in that plane. These results also have implications for the surgical
treatment of strabismus.
PMID- 9636120
TI - Role of the basal forebrain cholinergic projection in somatosensory cortical
plasticity.
AB - Trimming all but two whiskers in adult rats produces a predictable change in
cortical cell-evoked responses characterized by increased responsiveness to the
two intact whiskers and decreased responsiveness to the trimmed whiskers. This
type of synaptic plasticity in rat somatic sensory cortex, called "whisker
pairing plasticity," first appears in cells above and below the layer IV barrels.
These are also the cortical layers that receive the densest cholinergic inputs
from the nucleus basalis. The present study assesses whether the cholinergic
inputs to cortex have a role in regulating whisker pairing plasticity. To do
this, cholinergic basal forebrain fibers were eliminated using an immunotoxin
specific for these fibers. A monoclonal antibody to the low-affinity nerve growth
factor receptor 192 IgG, conjugated to the cytotoxin saporin, was injected into
cortex to eliminate cholinergic fibers in the barrel field. The immunotoxin
reduces acetylcholine esterase (AChE)-positive fibers in S1 cortex by >90% by 3
wk after injection. Sham-depleted animals in which either saporin alone or
saporin unconjugated to 192 IgG is injected into the cortex produces no decrease
in AChE-positive fibers in cortex. Sham-depleted animals show the expected
plasticity in barrel column neurons. In contrast, no plasticity develops in the
ACh-depleted, 7-day whisker-paired animals. These results support the conclusion
that the basal forebrain cholinergic projection to cortex is an important
facilitator of synaptic plasticity in mature cortex.
PMID- 9636121
TI - Synaptic connectivity of distinct hilar interneuron subpopulations.
AB - Dual intracellular recordings of hilar interneurons and CA3 pyramidal cells were
performed in transverse slices of guinea pig hippocampus in the presence of the
convulsant compound 4-aminopyridine (4-AP) and ionotropic glutamate receptor
antagonists. Under these conditions, interneurons burst fire synchronously,
producing synchronized inhibitory postsynaptic potentials (sIPSPs) in pyramidal
cells. Three different hilar interneuron subpopulations that contributed to the
sIPSP were identified based on their projection properties and morphology. These
three types were pyramidal-like stellate interneurons, spheroid interneurons, and
oviform interneurons. Physiologically, pyramidal-like stellate interneurons could
be differentiated from the other interneuron subpopulations because they
generated short synchronized bursts of action potentials coincident with the
hyperpolarizing and depolarizing gamma-aminobutyric acid-A (GABAA)-mediated
inhibitory postsynaptic potentials (IPSPs) recorded in pyramidal cells. The
bursts in pyramidal-like stellate cells were abolished by theGABAA-receptor
blocker, bicuculline. In contrast, spheroid interneurons of the dentate-hilus (D
H) border and oviform hilar interneurons exhibited prolonged bicuculline
resistant bursts that occurred coincident with the GABAB pyramidal cell sIPSPs.
Pyramidal-like stellate interneurons likely did not contribute to the generation
of synchronized GABAB responses in hippocampal pyramidal cells. Spheroid
interneurons were unique among these subpopulations of interneurons in that the
bicuculline-resistant bursts in spheroid interneurons were sustained by a
synaptic depolarization that persisted in the presence of antagonists of
ionotropic glutamate, GABAA and GABAB receptors [6-cyano-7-nitroquinoxaline-2,3
dione, 20 microM; 3-3(2-carboxipiperazine-4-yl)propyl-1-phosphonate, 20 microM;
bicuculline, 10-15 microM; CGP 55845A, 20 microM]. This novel depolarizing
potential reversed between -30 and 0 mV. No noticeable synaptic depolarization
sustaining burst firing could be isolated in oviform interneurons, suggesting
that firing in this interneuron subpopulation was synchronized by nonsynaptic
mechanisms. The results of the present study indicate that the hilar inhibitory
circuit is composed of at least three different subpopulations of interneurons,
distinguishable by their morphological characteristics and synaptic inputs and
outputs. These findings give further support to the hypothesis that there are
distinct populations of interneurons producing GABAA and GABAB responses with
defined functional roles within the hippocampal inhibitory circuit. Notably, we
found that spheroid interneurons were unique among the hilar interneurons
studied, in that the synchronized bursts observed in these cells are sustained by
a novel ionotropic glutamate and GABA receptor-independent synaptic
depolarization.
PMID- 9636122
TI - Encoding of shape and orientation of objects indented into the monkey fingerpad
by populations of slowly and rapidly adapting mechanoreceptors.
AB - The peripheral neural representation of object shape and orientation was studied
by recording the responses of a spatially distributed population of rapidly and
slowly adapting type I mechanoreceptors (RAs and SAs, respectively) to objects of
different shapes and orientations indented at a fixed location on the fingerpad
of the anesthetized monkey. The toroidal objects had a radius of 5 mm on the
major axis, and 1, 3, or 5 mm on the minor axis. Each object was indented into
the fingerpad for 4 s at orientations of 0, 45, 90, and 135 degrees using a
contact force of 15 gwt. Estimations of the population responses (PRs) were
constructed by combining the responses of 91 SA and 97 RA single afferents at
discrete times during the indentation. The PR was composed of the neural
discharge rates (z coordinate) plotted at x and y coordinates of the most
sensitive spot of the receptive field. The shapes of the PRs were related to the
shapes of the objects by fitting the PRs with Gaussian surfaces. The orientations
of the PRs were determined from weighted principal component analyses. The SA PR
encoded both the orientation and shape of the objects, whereas the RA PR did
neither. The SA PR orientation was biased toward the long axis of the finger. The
RA PR encoded orientation only for the object with the highest curvature but did
so ambiguously. Only the SA PR was well fit by a Gaussian surface. The shape of
the object was discriminated by the SA PR within the first 500 ms of contact, and
the form of the SA PR remained constant during the subsequent 3.5 s. This was
manifested by constant widths of the PR along the major and minor axes despite a
peak response that decreased from its maximum at 200 ms to an asymptotic value
starting at 1 s. Thus the shape and orientation of each object were coded by the
shape and orientation of the SA PR.
PMID- 9636124
TI - fMRI study of face perception and memory using random stimulus sequences.
AB - A new functional magnetic resonance imaging (fMRI) method was used to investigate
the functional neuroanatomy of face perception and memory. Whole-brain fMRI data
were acquired while four types of stimuli were presented sequentially in an
unpredictable pseudorandom order at a rate of 0.5 Hz. Stimulus types were a
single repeated memorized target face, unrepeated novel faces, nonsense scrambled
faces, and a blank screen. Random stimulus sequences were designed to generate a
functional response to each stimulus type that was uncorrelated with responses to
other stimuli. This allowed fMRI responses to each stimulus type to be examined
separately using multiple regression. Signal increases were found for all stimuli
in ventral posterior cortex. Responses to intact faces extended to more anterior
locations of occipitotemporal cortex than did responses to scrambled faces,
consistent with previous studies of face perception. Responses evoked by novel
faces were in regions of ventral occipitotemporal cortex medial to regions in
which significant responses were evoked by the target face. The repeated target
face stimulus also evoked activity in widely distributed regions of frontal and
parietal cortex. These results demonstrate that cortical hemodynamic responses to
interleaved novel and repeated stimuli can be distinguished and measured using
fMRI with appropriate stimulus sequences and data analysis methods. This method
can now be used to examine the neural systems involved in cognitive tasks that
were previously impossible to study using positron emission tomography or fMRI.
PMID- 9636123
TI - Modulation of the Ca2+-activated K+ current sIAHP by a phosphatase-kinase balance
under basal conditions in rat CA1 pyramidal neurons.
AB - The slow Ca2+-activated K+ current, sIAHP, underlying spike frequency adaptation,
was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons
in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases
(microcystin, calyculin A, cantharidic acid) caused a gradual decrease of sIAHP
amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation
turnover regulating sIAHP. Because selective calcineurin (PP-2B) inhibitors did
not affect the amplitude of sIAHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are
most likely involved in the basal regulation of this current. The ATP analogue,
ATP-gamma-S, caused a gradual decrease in the sIAHP amplitude, supporting a role
of protein phosphorylation in the basal modulation of sIAHP. When the protein
kinase A (PKA) inhibitor adenosine-3', 5'-monophosphorothioate, Rp-isomer (Rp
cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the
decrease in the sIAHP amplitude that was observed when microcystin alone was
applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the
sIAHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22, 536) and adenosine
3',5'-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20
1724 and rolipram) led to an increase or a decrease in the sIAHP amplitude,
respectively. These findings suggest that a balance between basally active PKA
and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of
sIAHP, resulting in a continuous modulation of excitability and firing properties
of hippocampal pyramidal neurons.
PMID- 9636125
TI - Role of platelet-activating factor in long-term potentiation of the rat medial
vestibular nuclei.
AB - In rat brain stem slices, we investigated the role of platelet activating factor
(PAF) in long-term potentiation (LTP) induced in the ventral part of the medial
vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary
vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was
administered before and after HFS. BN-52021 did not modify the vestibular
potentials under basal conditions, but it reduced the magnitude of potentiation
induced by HFS, which completely developed after the drug wash-out. The same
effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal
binding sites, but with concentrations higher than those of BN-52021. By contrast
both BN-52021 and CV-6209 had no effect on the potentiation once induced. This
demonstrates that PAF is involved in the induction but not in the maintenance of
vestibular long-term effect through activation of synaptosomal PAF receptors. In
addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O-
(methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF
metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular
responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation.
This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid,
suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under
BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose
effect curve of MC-PAF showed a shift to the right greater under BN-52021 than
under CV-6209, confirming the main dependence of MC-PAF potentiation on the
activation of synaptosomal PAF receptors. Our results suggest that PAF can be
released in the MVN after the activation of postsynaptic mechanisms triggering
LTP, and it may act as a retrograde messenger which activates the presynaptic
mechanisms facilitating synaptic plasticity.
PMID- 9636126
TI - Signal timing across the macaque visual system.
AB - The onset latencies of single-unit responses evoked by flashing visual stimuli
were measured in the parvocellular (P) and magnocellular (M) layers of the dorsal
lateral geniculate nucleus (LGNd) and in cortical visual areas V1, V2, V3, V4,
middle temporal area (MT), medial superior temporal area (MST), and in the
frontal eye field (FEF) in individual anesthetized monkeys. Identical procedures
were carried out to assess latencies in each area, often in the same monkey,
thereby permitting direct comparisons of timing across areas. This study presents
the visual flash-evoked latencies for cells in areas where such data are common
(V1 and V2), and are therefore a good standard, and also in areas where such data
are sparse (LGNd M and P layers, MT, V4) or entirely lacking (V3, MST, and FEF in
anesthetized preparation). Visual-evoked onset latencies were, on average, 17 ms
shorter in the LGNd M layers than in the LGNd P layers. Visual responses occurred
in V1 before any other cortical area. The next wave of activation occurred
concurrently in areas V3, MT, MST, and FEF. Visual response latencies in areas V2
and V4 were progressively later and more broadly distributed. These differences
in the time course of activation across the dorsal and ventral streams provide
important temporal constraints on theories of visual processing.
PMID- 9636127
TI - Trophic and contact conditions modulate synapse formation between identified
neurons.
AB - We tested the ability of an identified interneuron from the mollusk, Lymnaea
stagnalis, to reestablish appropriate synapses in vitro. In the CNS, the giant
dopaminergic neuron, designated as right pedal dorsal one (RPeD1), makes an
excitatory, chemical synapse with a pair of essentially identical postsynaptic
cells known as visceral dorsal two and three (VD2/3). When the somata of the pre-
and postsynaptic neurons were juxtaposed and cultured in vitro in defined medium,
i.e. , a soma-soma synapse, only an inappropriate electrical synapse was
observed. The postsynaptic cell still responded to applied dopamine, the
presynaptic transmitter, indicating that the lack of chemical synapse formation
was not due to lack of dopamine receptors. When the somata were cultured apart in
conditioned medium (medium previously incubated with Lymnaea CNS, thereby
deriving trophic factors), the cells exhibited overlapping neurite outgrowth that
resulted in an appropriate excitatory, chemical synapse from RPeD1 to VD2/3. On
the other hand, when the cell pair was cultured in a soma-soma configuration, but
in conditioned medium, a mixed chemical-electrical synapse was observed. Because
conditioned medium could partially overcome the limitations of the soma-soma
configuration and initiate chemical synapse formation, this data suggests that
conditioned medium contains a factor(s) that supports synaptogenesis.
PMID- 9636128
TI - Periodicity of thalamic spindle waves is abolished by ZD7288,a blocker of Ih.
AB - The actions of the novel bradycardiac agent ZD7288 [4-(N-ethyl-N-phenylamino)-1,
2-dimethyl-6-(methylamino)pyrimidinium chloride] were investigated on the
hyperpolarization-activated cation current Ih and on network activity in
spontaneously spindling ferret lateral geniculate (LGNd) slices in vitro using
intracellular recording techniques. In voltage-clamp recordings, local
application of ZD7288 (1 mM in micropipette) resulted in a complete block of Ih,
whereas in current-clamp recordings, application of this agent resulted in an
abolition of the depolarizing sag activated by hyperpolarization and decreased
the frequency of intrinsic delta-oscillations for which Ih acts as a pacemaker
current. In addition, block of Ih with ZD7288 resulted in an abolition of the
afterdepolarization (ADP) that follows repetitive hyperpolarization and rebound
burst firing as well as that occurring in between spindle waves. The block of the
ADP was associated with a block of the spindle wave refractory period such that
continuous 6- to 10-Hz oscillations were generated throughout the network. These
findings give further support to the hypothesis that Ih is critically involved in
the generation of slow rhythmicity in synchronized thalamic activity.
PMID- 9636129
TI - Pointing errors reflect biases in the perception of the initial hand position.
AB - By comparing the visuomotor performance of 10 adult, normal subjects in three
tasks, we investigated whether errors in pointing movements reflect biased
estimations of the hand starting position. In a manual pointing task with no
visual feedback, subjects aimed at 48 targets spaced regularly around two
starting positions. Nine subjects exhibited a similar pattern of systematic
errors across targets, i.e., a parallel shift of the end points that accounted,
on average, for 49% of the total variability. The direction of the shift depended
on the starting location. Systematic errors decreased dramatically in the second
condition where subjects were allowed to see their hand before movement onset.
The third task was to use a joystick held by the left hand to estimate the
location of their (unseen) right hand. The systematic perceptual errors in this
condition were found to be highly correlated with the motor errors in the first
condition. The results support the following conclusions. 1) Kinesthetic
estimation of hand position may be consistently biased. Some of the mechanisms
responsible for these biases are always active, irrespective of whether position
is estimated overtly (e.g., with a matching paradigm), or covertly as part of the
motor planning for aimed movements. 2) Pointing errors reflect to a significant
extent the erroneous estimation of initial hand position. This suggests that
aimed hand movements are planned vectorially, i.e., in terms of distance and
direction, rather than in terms of absolute position in space.
PMID- 9636130
TI - Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic
nucleotide-gated channel type 1 null mouse.
AB - Field potential recording was used to investigate properties of synaptic
transmission and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses
in both hippocampal slices of mutant mice in which the alpha-subunit of the
olfactory cyclic nucleotide-gated channel (alpha3/OCNC)1 was rendered null and
also in slices prepared from their wild-type (Wt) littermates. Several measures
of basal synaptic transmission were unaltered in the OCNC1 knockout (KO),
including maximum field excitatory postsynaptic potential (fEPSP) slope, maximum
fEPSP and fiber volley amplitude, and the function relating fiber volley
amplitude to fEPSP slope and paired-pulse facilitation. When a high-frequency
stimulation protocol was used to induce LTP, similar responses were seen in both
groups [KO: 1 min, 299 +/- 50% (mean +/- SE), 60 min, 123 +/- 10%; Wt: 1 min, 287
+/- 63%; 60 min, 132 +/- 19%). However, on theta-burst stimulation, the initial
amplitude of LTP was smaller (1 min after induction, 147 +/- 16% of baseline) and
the response decayed faster in the OCNC1 KO (60 min, 127 +/- 18%) than in Wt (1
min, 200 +/- 14%; 60 min, 169 +/- 19%). Analysis of waveforms evoked by LTP
inducing tetanic stimuli revealed a similar difference between groups. The
development of potentiation throughout the tetanic stimulus was similar in OCNC1
KO and Wt mice when high-frequency stimulation was used, but OCNC1 KO mice showed
a significant decrease when compared with Wt mice receiving theta-burst
stimulation. These results suggest that activation of cyclic nucleotide-gated
channels may contribute to the induction of LTP by weaker, more physiological
stimuli, possibly via Ca2+ influx.
PMID- 9636131
TI - Form follows function: structure of an elongation factor G-ribosome complex.
PMID- 9636132
TI - Three independent lines of evidence suggest retinoids as causal to schizophrenia.
AB - Retinoid dysregulation may be an important factor in the etiology of
schizophrenia. This hypothesis is supported by three independent lines of
evidence that triangulate on retinoid involvement in schizophrenia: (i)
congenital anomalies similar to those caused by retinoid dysfunction are found in
schizophrenics and their relatives; (ii) those loci that have been suggestively
linked to schizophrenia are also the loci of the genes of the retinoid cascade
(convergent loci); and (iii) the transcriptional activation of the dopamine D2
receptor and numerous schizophrenia candidate genes is regulated by retinoic
acid. These findings suggest a close causal relationship between retinoids and
the underlying pathophysiological defects in schizophrenia. This leads to
specific strategies for linkage analyses in schizophrenia. In view of the
heterodimeric nature of the retinoid nuclear receptor transcription factors,
e.g., retinoid X receptor beta at chromosome 6p21.3 and retinoic acid receptor
beta at 3p24.3, two-locus linkage models incorporating genes of the retinoid
cascade and their heterodimeric partners, e.g., peroxisome proliferator-activated
receptor alpha at chromosome 22q12-q13 or nuclear-related receptor 1 at
chromosome 2q22-q23, are proposed. New treatment modalities using retinoid
analogs to alter the downstream expression of the dopamine receptors and other
genes that are targets of retinoid regulation, and that are thought to be
involved in schizophrenia, are suggested.
PMID- 9636133
TI - A coupled proton-transfer and twisting-motion fluorescence probe for lipid
bilayers.
AB - A new and sensitive molecular probe, 2-(2'-hydroxyphenyl)imidazo[1, 2-a]pyridine
(HPIP), for monitoring structural changes in lipid bilayers is presented.
Migration of HPIP from water into vesicles involves rupture of hydrogen (H) bonds
with water and formation of an internal H bond once the probe is inside the
vesicle. These structural changes of the dye allow the occurrence of a
photoinduced intramolecular proton-transfer reaction and a subsequent
twisting/rotational process upon electronic excitation of the probe. The
resulting large Stokes-shifted fluorescence band depends on the twisting motion
of the zwitterionic phototautomer and is characterized in vesicles of dimyristoyl
phosphatidylcholine and in dipalmitoyl-phosphatidylcholine at the temperature
range of interest and in the presence of cholesterol. Because the fluorescence of
aqueous HPIP does not interfere in the emission of the probe within the vesicles,
HPIP proton-transfer/twisting motion fluorescence directly allows us to monitor
and quantify structural changes within bilayers. The static and dynamic
fluorescence parameters are sensitive enough to such changes to suggest this
photostable dye as a potential molecular probe of the physical properties of
lipid bilayers.
PMID- 9636134
TI - Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of
RNase T1.
AB - An antibody generated to an alpha-keto amide containing hapten 1 catalyzes the
cis-trans isomerization of peptidyl-prolyl amide bonds in peptides and in the
protein RNase T1. The antibody-catalyzed peptide isomerization reaction showed
saturation kinetics for the cis-substrate, Suc-Ala-Ala-Pro-Phe-pNA, with a
kcat/Km value of 883 s-1.M-1; the reaction was inhibited by the hapten analog 13
(Ki = 3. 0 +/- 0.4 microM). Refolding of denatured RNase T1 to its native
conformation also was catalyzed by the antibody, with the antibody-catalyzed
folding reaction inhibitable both by the hapten 1 and hapten analog 13. These
results demonstrate that antibodies can catalyze conformational changes in
protein structure, a transformation involved in many cellular processes.
PMID- 9636135
TI - Calculated 11B-13C NMR chemical shift relationship in hypercoordinate methonium
and boronium ions.
AB - The boronium-carbonium continuum was extended to include hypercoordinated
protonated methanes and their boron analogs. The 11B NMR chemical shifts of the
hypercoordinated hydriodo boron compounds and the 13C NMR chemical shifts of the
corresponding isoelectronic and isostructural carbocations were calculated by
using the GIAO-MP2 method. The data show good linear correlation between 11B and
13C NMR chemical shifts, which indicates that the same factors that determine the
chemical shifts of the boron nuclei also govern the chemical shifts of carbon
nuclei of these hypercoordinated hydriodo compounds.
PMID- 9636136
TI - Oceanic protection of prebiotic organic compounds from UV radiation.
AB - It is frequently stated that UV light would cause massive destruction of
prebiotic organic compounds because of the absence of an ozone layer. The
elevated UV flux of the early sun compounds this problem. This applies to organic
compounds of both terrestrial and extraterrestrial origin. Attempts to deal with
this problem generally involve atmospheric absorbers. We show here that prebiotic
organic polymers as well as several inorganic compounds are sufficient to protect
oceanic organic molecules from UV degradation. This aqueous protection is in
addition to any atmospheric UV absorbers and should be a ubiquitous planetary
phenomenon serving to increase the size of planetary habitable zones.
PMID- 9636137
TI - Broken symmetry and strangeness of the semiconductor impurity band metal
insulator transition.
AB - The filamentary model of the metal-insulator transition in randomly doped
semiconductor impurity bands is geometrically equivalent to similar models for
continuous transitions in dilute antiferromagnets and even to the lambda
transition in liquid He, but the critical behaviors are different. The origin of
these differences lies in two factors: quantum statistics and the presence of
long range Coulomb forces on both sides of the transition in the electrical case.
In the latter case, in addition to the main transition, there are two satellite
transitions associated with disappearance of the filamentary structure in both
insulating and metallic phases. These two satellite transitions were first
identified by Fritzsche in 1958, and their physical origin is explained here in
geometrical and topological terms that facilitate calculation of critical
exponents.
PMID- 9636138
TI - A stochastic approximation algorithm with Markov chain Monte-carlo method for
incomplete data estimation problems.
AB - We propose a general procedure for solving incomplete data estimation problems.
The procedure can be used to find the maximum likelihood estimate or to solve
estimating equations in difficult cases such as estimation with the censored or
truncated regression model, the nonlinear structural measurement error model, and
the random effects model. The procedure is based on the general principle of
stochastic approximation and the Markov chain Monte-Carlo method. Applying the
theory on adaptive algorithms, we derive conditions under which the proposed
procedure converges. Simulation studies also indicate that the proposed procedure
consistently converges to the maximum likelihood estimate for the structural
measurement error logistic regression model.
PMID- 9636139
TI - Defining the domains of type I collagen involved in heparin- binding and
endothelial tube formation.
AB - Cell surface heparan sulfate proteoglycan (HSPG) interactions with type I
collagen may be a ubiquitous cell adhesion mechanism. However, the HSPG binding
sites on type I collagen are unknown. Previously we mapped heparin binding to the
vicinity of the type I collagen N terminus by electron microscopy. The present
study has identified type I collagen sequences used for heparin binding and
endothelial cell-collagen interactions. Using affinity coelectrophoresis, we
found heparin to bind as follows: to type I collagen with high affinity (Kd
approximately 150 nM); triple-helical peptides (THPs) including the basic N
terminal sequence alpha1(I)87-92, KGHRGF, with intermediate affinities (Kd
approximately 2 microM); and THPs including other collagenous sequences, or
single-stranded sequences, negligibly (Kd >> 10 microM). Thus, heparin-type I
collagen binding likely relies on an N-terminal basic triple-helical domain
represented once within each monomer, and at multiple sites within fibrils. We
next defined the features of type I collagen necessary for angiogenesis in a
system in which type I collagen and heparin rapidly induce endothelial tube
formation in vitro. When peptides, denatured or monomeric type I collagen, or
type V collagen was substituted for type I collagen, no tubes formed. However,
when peptides and type I collagen were tested together, only the most heparin
avid THPs inhibited tube formation, likely by influencing cell interactions with
collagen-heparin complexes. Thus, induction of endothelial tube morphogenesis by
type I collagen may depend upon its triple-helical and fibrillar conformations
and on the N-terminal heparin-binding site identified here.
PMID- 9636140
TI - Tyrosine phosphorylation of paxillin and focal adhesion kinase by activation of
muscarinic m3 receptors is dependent on integrin engagement by the extracellular
matrix.
AB - The G protein-coupled m1 and m3 muscarinic acetylcholine receptors increase
tyrosine phosphorylation of several proteins, including the focal adhesion
associated proteins paxillin and focal adhesion kinase (FAK), but the mechanism
is not understood. Activation of integrins during adhesion of cells to
extracellular matrix, or stimulation of quiescent cell monolayers with G protein
coupled receptor ligands including bradykinin, bombesin, endothelin, vasopressin,
and lysophosphatidic acid, also induces tyrosine phosphorylation of paxillin and
FAK and formation of focal adhesions. These effects are generally independent of
protein kinase C but are inhibited by agents that prevent cytoskeletal assembly
or block activation of the small molecular weight G protein Rho. This report
demonstrates that tyrosine phosphorylation of paxillin and FAK elicited by
stimulation of muscarinic m3 receptors with the acetylcholine analog carbachol is
inhibited by soluble peptides containing the arginine-glycine-aspartate motif
(the recognition site for integrins found in adhesion proteins such as
fibronectin) but is unaffected by peptides containing the inactive sequence
arginine-glycine-glutamate. Tyrosine phosphorylation elicited by carbachol, but
not by cell adhesion to fibronectin, is reduced by the protein kinase C inhibitor
GF 109203X. The response to carbachol is dependent on the presence of
fibronectin. Moreover, immunofluorescence studies show that carbachol treatment
induces formation of stress fibers and focal adhesions. These results suggest
that muscarinic receptor stimulation activates integrins via a protein kinase C
dependent mechanism. The activated integrins transmit a signal into the cell's
interior leading to tyrosine phosphorylation of paxillin and FAK. This represents
a novel mechanism for regulation of tyrosine phosphorylation by muscarinic
receptors.
PMID- 9636141
TI - A synthetic all D-amino acid peptide corresponding to the N-terminal sequence of
HIV-1 gp41 recognizes the wild-type fusion peptide in the membrane and inhibits
HIV-1 envelope glycoprotein-mediated cell fusion.
AB - Recent studies demonstrated that a synthetic fusion peptide of HIV-1 self
associates in phospholipid membranes and inhibits HIV-1 envelope glycoprotein
mediated cell fusion, presumably by interacting with the N-terminal domain of
gp41 and forming inactive heteroaggregates [Kliger, Y., Aharoni, A., Rapaport,
D., Jones, P., Blumenthal, R. & Shai, Y. (1997) J. Biol. Chem. 272, 13496-13505].
Here, we show that a synthetic all D-amino acid peptide corresponding to the N
terminal sequence of HIV-1 gp41 (D-WT) of HIV-1 associates with its enantiomeric
wild-type fusion (WT) peptide in the membrane and inhibits cell fusion mediated
by the HIV-1 envelope glycoprotein. D-WT does not inhibit cell fusion mediated by
the HIV-2 envelope glycoprotein. WT and D-WT are equally potent in inducing
membrane fusion. D-WT peptide but not WT peptide is resistant to proteolytic
digestion. Structural analysis showed that the CD spectra of D-WT in
trifluoroethanol/water is a mirror image of that of WT, and attenuated total
reflectance-fourier transform infrared spectroscopy revealed similar structures
and orientation for the two enantiomers in the membrane. The results reveal that
the chirality of the synthetic peptide corresponding to the HIV-1 gp41 N-terminal
sequence does not play a role in liposome fusion and that the peptides' chirality
is not necessarily required for peptide-peptide interaction within the membrane
environment. Furthermore, studies along these lines may provide criteria to
design protease-resistant therapeutic agents against HIV and other viruses.
PMID- 9636142
TI - alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin:
application as an antipathogenic agent.
AB - The important role of furin in the proteolytic activation of many pathogenic
molecules has made this endoprotease a target for the development of potent and
selective antiproteolytic agents. Here, we demonstrate the utility of the protein
based inhibitor alpha1-antitrypsin Portland (alpha1-PDX) as an antipathogenic
agent that can be used prophylactically to block furin-dependent cell killing by
Pseudomonas exotoxin A. Biochemical analysis of the specificity of a bacterially
expressed His- and FLAG-tagged alpha1-PDX (alpha1-PDX/hf) revealed the
selectivity of the alpha1-PDX/hf reactive site loop for furin (Ki, 600 pM) but
not for other proprotein convertase family members or other unrelated
endoproteases. Kinetic studies show that alpha1-PDX/hf inhibits furin by a slow
tight-binding mechanism characteristic of serpin molecules and functions as a
suicide substrate inhibitor. Once bound to furin's active site, alpha1-PDX/hf
partitions with equal probability to undergo proteolysis by furin at the C
terminal side of the reactive center -Arg355-Ile-Pro-Arg358- downward arrow or to
form a kinetically trapped SDS-stable complex with the enzyme. This partitioning
between the complex-forming and proteolytic pathways contributes to the ability
of alpha1-PDX/hf to differentially inhibit members of the proprotein convertase
family. Finally, we propose a structural model of the alpha1-PDX-reactive site
loop that explains the high degree of enzyme selectivity of this serpin and which
can be used to generate small molecule furin inhibitors.
PMID- 9636143
TI - Supramolecular organization of immature and mature murine leukemia virus revealed
by electron cryo-microscopy: implications for retroviral assembly mechanisms.
AB - We have used electron cryo-microscopy and image analysis to examine the native
structure of immature, protease-deficient (PR-) and mature, wild-type (WT)
Moloney murine leukemia virus (MuLV). Maturational cleavage of the Gag
polyprotein by the viral protease is associated with striking morphological
changes. The PR- MuLV particles exhibit a rounded central core, which has a
characteristic track-like shell on its surface, whereas the WT MuLV cores display
a polygonal surface with loss of the track-like feature. The pleomorphic shape
and inability to refine unique orientation angles suggest that neither the PR-
nor the WT MuLV adheres to strict icosahedral symmetry. Nevertheless, the PR-
MuLV particles do exhibit paracrystalline order with a spacing between Gag
molecules of approximately 45 A and a length of approximately 200 A. Because of
the pleomorphic shape and paracrystalline packing of the Gag-RNA complexes, we
raise the possibility that assembly of MuLV is driven by protein-RNA, as well as
protein-protein, interactions. The maturation process involves a dramatic
reorganization of the packing arrangements within the ribonucleoprotein core with
disordering and loosening of the individual protein components.
PMID- 9636144
TI - Ethyl-substituted erythromycin derivatives produced by directed metabolic
engineering.
AB - A previously unknown chemical structure, 6-desmethyl-6-ethylerythromycin A (6
ethylErA), was produced through directed genetic manipulation of the erythromycin
(Er)-producing organism Saccharopolyspora erythraea. In an attempt to replace the
methyl side chain at the C-6 position of the Er polyketide backbone with an ethyl
moiety, the methylmalonate-specific acyltransferase (AT) domain of the Er
polyketide synthase was replaced with an ethylmalonate-specific AT domain from
the polyketide synthase involved in the synthesis of the 16-member macrolide
niddamycin. The genetically altered strain was found to produce ErA, however, and
not the ethyl-substituted derivative. When the strain was provided with
precursors of ethylmalonate, a small quantity of a macrolide with the mass of 6
ethylErA was produced in addition to ErA. Because substrate for the heterologous
AT seemed to be limiting, crotonyl-CoA reductase, a primary metabolic enzyme
involved in butyryl-CoA production in streptomycetes, was expressed in the
strain. The primary macrolide produced by the reengineered strain was 6-ethylErA.
PMID- 9636145
TI - A model for the structure of the P domains in the subtilisin-like prohormone
convertases.
AB - The proprotein convertases are a family of at least seven calcium-dependent
endoproteases that process a wide variety of precursor proteins in the secretory
pathway. All members of this family possess an N-terminal proregion, a subtilisin
like catalytic module, and an additional downstream well-conserved region of
approximately 150 amino acid residues, the P domain, which is not found in any
other subtilase. The pro and catalytic domains cannot be expressed in the absence
of the P domains; their thermodynamic instability may be attributable to the
presence of large numbers of negatively charged Glu and Asp side chains in the
substrate binding region for recognition of multibasic residue cleavage sites.
Based on secondary structure predictions, we here propose that the P domains
consist of 8-stranded beta-barrels with well-organized inner hydrophobic cores,
and therefore are independently folded components of the proprotein convertases.
We hypothesize further that the P domains are integrated through strong
hydrophobic interactions with the catalytic domains, conferring structural
stability and regulating the properties and activity of the convertases. A
molecular model of these interdomain interactions is proposed in this report.
PMID- 9636146
TI - Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia
associated nuclear bodies and the chromatin compartment.
AB - The PML/SP100 nuclear bodies (NBs) were first described as discrete subnuclear
structures containing the SP100 protein. Subsequently, they were shown to contain
the PML protein which is part of the oncogenic PML-RARalpha hybrid produced by
the t(15;17) chromosomal translocation characteristic of acute promyelocytic
leukemia. Yet, the physiological role of these nuclear bodies remains unknown.
Here, we show that SP100 binds to members of the heterochromatin protein 1 (HP1)
families of non-histone chromosomal proteins. Further, we demonstrate that a
naturally occurring splice variant of SP100, here called SP100-HMG, is a member
of the high mobility group-1 (HMG-1) protein family and may thus possess DNA
binding potential. Both HP1 and SP100-HMG concentrate in the PML/SP100 NBs, and
overexpression of SP100 leads to enhanced accumulation of endogenous HP1 in these
structures. When bound to a promoter, SP100, SP100-HMG and HP1 behave as
transcriptional repressors in transfected mammalian cells. These observations
present molecular evidence for an association between the PML/SP100 NBs and the
chromatin nuclear compartment. They support a model in which the NBs may play a
role in certain aspects of chromatin dynamics.
PMID- 9636147
TI - Chromatin components as part of a putative transcriptional repressing complex.
AB - The Drosophila HMG1-like protein DSP1 was identified by its ability to inhibit
the transcriptional activating function of Dorsal in a promoter-specific fashion
in yeast. We show here that DSP1 as well as its mammalian homolog hHMG2 bind to
the mammalian protein SP100B and that SP100B in turn binds to human homologs of
HP1. The latter is a Drosophila protein that is involved in transcriptional
silencing. Each of these proteins represses transcription when tethered to DNA in
mammalian cells. These results suggest how heterochromatin proteins might be
recruited to specific sites on DNA with resultant specific effects on gene
expression.
PMID- 9636148
TI - Effective inhibition of influenza virus production in cultured cells by external
guide sequences and ribonuclease P.
AB - The polymerase (PB2) and nucleocapsid (NP) genes encoded by the genome of
influenza virus are essential for replication of the virus. When synthetic genes
that express RNAs for external guide sequences targeted to the mRNAs of the PB2
and NP genes are stably incorporated into mouse cells in tissue culture,
infection of these cells with influenza virus is nonproductive. Endogenous RNase
P cleaves the targeted influenza virus mRNAs when they are in a complex with the
external guide sequences. Targeting two different mRNAs simultaneously inhibits
viral particle production more efficiently than does targeting only one mRNA.
PMID- 9636149
TI - Two binding modes reveal flexibility in kinase/response regulator interactions in
the bacterial chemotaxis pathway.
AB - The crystal structure at 2.0-A resolution of the complex of the Escherichia coli
chemotaxis response regulator CheY and the phosphoacceptor-binding domain (P2) of
the kinase CheA is presented. The binding interface involves the fourth and fifth
helices and fifth beta-strand of CheY and both helices of P2. Surprisingly, the
two heterodimers in the asymmetric unit have two different binding modes
involving the same interface, suggesting some flexibility in the binding regions.
Significant conformational changes have occurred in CheY compared with previously
determined unbound structures. The active site of CheY is exposed by the binding
of the kinase domain, possibly to enhance phosphotransfer from CheA to CheY. The
conformational changes upon complex formation as well as the observation that
there are two different binding modes suggest that the plasticity of CheY is an
essential feature of response regulator function.
PMID- 9636150
TI - The N-terminal domain of PsaF: precise recognition site for binding and fast
electron transfer from cytochrome c6 and plastocyanin to photosystem I of
Chlamydomonas reinhardtii.
AB - The PsaF-deficient mutant 3bF of Chlamydomonas reinhardtii was used to modify
PsaF by nuclear transformation and site-directed mutagenesis. Four lysine
residues in the N-terminal domain of PsaF, which have been postulated to form the
positively charged face of a putative amphipathic alpha-helical structure were
altered to K12P, K16Q, K23Q, and K30Q. The interactions between plastocyanin (pc)
or cytochrome c6 (cyt c6) and photosystem I (PSI) isolated from wild type and the
different mutants were analyzed using crosslinking techniques and flash
absorption spectroscopy. The K23Q change drastically affected crosslinking of pc
to PSI and electron transfer from pc and cyt c6 to PSI. The corresponding second
order rate constants for binding of pc and cyt c6 were reduced by a factor of 13
and 7, respectively. Smaller effects were observed for mutations K16Q and K30Q,
whereas in K12P the binding was not changed relative to wild type. None of the
mutations affected the half-life of the microsecond electron transfer performed
within the intermolecular complex between the donors and PSI. The fact that these
single amino acid changes within the N-terminal domain of PsaF have different
effects on the electron transfer rate constants and dissociation constants for
both electron donors suggests the existence of a rather precise recognition site
for pc and cyt c6 that leads to the stabilization of the final electron transfer
complex through electrostatic interactions.
PMID- 9636151
TI - Tn552 transposase catalyzes concerted strand transfer in vitro.
AB - The Tn552 transposase, a member of the DDE superfamily of transposase and
retroviral integrase proteins, has been expressed in soluble form. The purified
protein performs concerted strand transfer in vitro, efficiently pairing two
preprocessed transposon ends and inserting them into target DNA. For maximum
efficiency, both participating DNA ends must contain the two adjacent transposase
binding sites that are the normal constituents of the Tn552 termini. As is the
case with transposition in vivo, the insertions recovered from the reaction in
vitro are flanked by repeats of a short target sequence, most frequently 6 bp.
The reaction has stringent requirements for a divalent metal ion. Concerted
strand transfer is most efficient with Mg2+. Although it stimulates strand
transfer overall, Mn2+ promotes uncoupled, single-ended events at the expense of
concerted insertions. The simplicity and efficiency of the Tn552 transposition
system make it an attractive subject for structural and biochemical studies and a
potentially useful genetic tool.
PMID- 9636152
TI - Malignant transformation of early lymphoid progenitors in mice expressing an
activated Blk tyrosine kinase.
AB - The intracellular signals governing cellular proliferation and developmental
progression during lymphocyte development are incompletely understood. The
tyrosine kinase Blk is expressed preferentially in the B lineage, but its
function in B cell development has been largely unexplored. We have generated
transgenic mice expressing constitutively active Blk [Blk(Y495F)] in the B and T
lymphoid compartments. Expression of Blk(Y495F) in the B lineage at levels
similar to that of endogenous Blk induced B lymphoid tumors of limited clonality,
whose phenotypes are characteristic of B cell progenitors at the proB/preB-I to
preB-II transition. Expression of constitutively active Blk in the T lineage
resulted in the appearance of clonal, thymic lymphomas composed of intermediate
single positive cells. Taken together, these results indicate that specific B and
T cell progenitor subsets are preferentially susceptible to transformation by
Blk(Y495F) and suggest a role for Blk in the control of proliferation during B
cell development.
PMID- 9636153
TI - The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p
Ser/Thr protein phosphatase.
AB - Components of cellular stress responses can be identified by correlating changes
in stress tolerance with gain or loss of function of defined genes. Previous work
has shown that yeast cells deficient in Ppz1 protein phosphatase or
overexpressing Hal3p, a novel regulatory protein of unknown function, exhibit
increased resistance to sodium and lithium, whereas cells lacking Hal3p display
increased sensitivity. These effects are largely a result of changes in
expression of ENA1, encoding the major cation extrusion pump of yeast cells.
Disruption or overexpression of HAL3 (also known as SIS2) has no effect on salt
tolerance in the absence of PPZ1, suggesting that Hal3p might function upstream
of Ppz1p in a novel signal transduction pathway. Hal3p is recovered from crude
yeast homogenates by using immobilized, bacterially expressed Ppz1p fused to
glutathione S-transferase, and it also copurifies with affinity-purified
glutathione S-transferase-Ppz1p from yeast extracts. In both cases, the
interaction is stronger when only the carboxyl-terminal catalytic phosphatase
domain of Ppz1p is expressed. In vitro experiments reveal that the protein
phosphatase activity of Ppz1p is inhibited by Hal3p. Overexpression of Hal3p
suppresses the reduced growth rate because of the overexpression of Ppz1p and
aggravates the lytic phenotype of a slt2/mpk1 mitogen-activated protein kinase
mutant (thus mimicking the deletion of PPZ1). Therefore, Hal3p might modulate
diverse physiological functions of the Ppz1 phosphatase, such as salt stress
tolerance and cell cycle progression, by acting as a inhibitory subunit.
PMID- 9636154
TI - In disperse solution, "osmotic stress" is a restricted case of preferential
interactions.
AB - In the practice of "osmotic stress," the effect of excluded cosolvents on a
biochemical equilibrium is interpreted as the number of water molecules
participating in the reaction. This action is attributed to lowering of solvent
water activity by the cosolvent. This concept of osmotic stress in disperse
solution is erroneous: (i) A cosolvent cannot be both excluded and inert, i.e.,
noninteracting, because exclusion requires a positive free energy change; (ii) a
decrease in water activity alone by addition of solute cannot affect an
equilibrium when the reacting surface is in contact with the solvent; and (iii)
osmotic stress in disperse solution is a restricted case of preferential
interactions; the reaction is driven by the free energy of cosolvent exclusion,
and the derived number of water molecules is solely a measure of the mutual
perturbations of the chemical potentials of the cosolvent and the protein.
PMID- 9636155
TI - Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in
hypoxia.
AB - Nitric oxide (NO) is known to have various biologic and pathophysiologic effects
on organisms. The molecular mechanisms by which NO exerts harmful effects are
unknown, although various O2 radicals and ions that result from reactivity of NO
are presumed to be involved. Here we report that adaptive cellular response
controlled by the transcription factor hypoxia-inducible factor 1 (HIF-1) in
hypoxia is suppressed by NO. Induction of erythropoietin and glycolytic aldolase
A mRNAs in hypoxically cultured Hep3B cells, a human hepatoma cell line, was
completely and partially inhibited, respectively, by the addition of sodium
nitroprusside (SNP), which spontaneously releases NO. A reporter plasmid carrying
four hypoxia-response element sequences connected to the luciferase structural
gene was constructed and transfected into Hep3B cells. Inducibly expressed
luciferase activity in hypoxia was inhibited by the addition of SNP and two other
structurally different NO donors, S-nitroso-L-glutathione and 3
morpholinosydnonimine, giving IC50 values of 7.8, 211, and 490 microM,
respectively. Inhibition by SNP was also observed in Neuro 2A and HeLa cells,
indicating that the inhibition was not cell-type-specific. The vascular
endothelial growth factor promoter activity that is controlled by HIF-1 was also
inhibited by SNP (IC50 = 6.6 microM). Induction generated by the addition of
cobalt ion (this treatment mimics hypoxia) was also inhibited by SNP (IC50 = 2.5
microM). Increased luciferase activity expressed by cotransfection of effector
plasmids for HIF-1alpha or HIF-1alpha-like factor in hypoxia was also inhibited
by the NO donor. We also showed that the inhibition was performed by blocking an
activation step of HIF-1alpha to a DNA-binding form.
PMID- 9636156
TI - Characterization of genes modulated during pheomelanogenesis using differential
display.
AB - Molecular and biochemical mechanisms that modulate the production of eumelanin or
pheomelanin pigments involve the opposing effects of two intercellular signaling
molecules, alpha-melanocyte stimulating hormone (MSH) and agouti signal protein
(ASP). ASP is an antagonist of MSH signaling through the melanocyte-specific MSH
receptor, although its mechanism(s) of action is controversial. We previously
have reported significant down-regulation of all known melanogenic genes during
the eumelanin to pheomelanin switch in murine hair follicle melanocytes and in
cultured melanocytes treated with recombinant ASP. To identify factors that might
be involved in the switch to pheomelanogenesis, we screened ASP-treated
melanocytes by using differential display and identified three up-regulated
genes: a DNA replication control protein, a basic helix-loop-helix transcription
factor, and a novel gene. We have simultaneously identified six down-regulated
genes in ASP-treated melanocytes; two of those encode tyrosinase and TRP2,
melanogenic genes known to be down-regulated during pheomelanogenesis, which
provide good internal controls for this approach. These results suggest that
there are complex mechanisms involved in the switch to pheomelanin production,
and that these modulated genes might be involved in the pleiotropic changes seen
in yellow mice, including the change in coat color.
PMID- 9636157
TI - Promotion of agonist activity of antiandrogens by the androgen receptor
coactivator, ARA70, in human prostate cancer DU145 cells.
AB - Although hormone therapy with antiandrogens has been widely used for the
treatment of prostate cancer, some antiandrogens may act as androgen receptor
(AR) agonists that may result in antiandrogen withdrawal syndrome. The molecular
mechanism of this agonist response, however, remains unclear. Using mammalian two
hybrid assay, we report that antiandrogens, hydroxyflutamide, bicalutamide
(casodex), cyproterone acetate, and RU58841, and other compounds such as
genistein and RU486, can promote the interaction between AR and its coactivator,
ARA70, in a dose-dependent manner. The chloramphenicol acetyltransferase assay
further demonstrates that these antiandrogens and related compounds significantly
enhance the AR transcriptional activity by cotransfection of AR and ARA70 in a
1:3 ratio into human prostate cancer DU145 cells. Our results suggest that the
agonist activity of antiandrogens might occur with the proper interaction of AR
and ARA70 in DU145 cells. These findings may provide a good model to develop
better antiandrogens without agonist activity.
PMID- 9636158
TI - 13C NMR study of the effects of leptin treatment on kinetics of hepatic
intermediary metabolism.
AB - The recent discovery of leptin receptors in peripheral tissue raises questions
about which of leptin's biological actions arise from direct effects of the
hormone on extraneural tissues and what intracellular mechanisms are responsible
for leptin's effects on carbohydrate and lipid metabolism. The present study is
focused on the action of leptin on hepatic metabolism. Nondestructive 13C NMR
methodology was used to follow the kinetics of intermediary metabolism by
monitoring flux of 13C-labeled substrate through several multistep pathways. In
perfused liver from either ob/ob or lean mice, we found that acute treatment with
leptin in vitro modulates pathways controlling carbohydrate flux into 13C-labeled
glycogen, thereby rapidly enhancing synthesis by an insulin-independent
mechanism. Acute treatment of ob/ob liver also caused a rapid stimulation of long
chain fatty acid synthesis from 13C-labeled acetyl-CoA by the de novo synthesis
route. Chronic leptin treatment in vivo induced homeostatic changes that resulted
in a tripling of the rate of glycogen synthesis via the gluconeogenic pathway
from [2-13C]pyruvate in ob/ob mouse liver perfused in the absence of the hormone.
Consistent with the 13C NMR results, leptin treatment of the ob/ob mouse in vivo
resulted in significantly increased hepatic glycogen synthase activity. Chronic
treatment with leptin in vivo exerted the opposite effect of acute treatment in
vitro and markedly decreased hepatic de novo synthesis of fatty acids in ob/ob
mouse liver. In agreement with the 13C NMR findings, activities of hepatic acetyl
CoA carboxylase and fatty acid synthase were significantly reduced by chronic
treatment of the ob/ob mouse with leptin. Our data represent a demonstration of
direct effects of leptin in the regulation of metabolism in the intact
functioning liver.
PMID- 9636159
TI - Mass spectrometry of ribosomes and ribosomal subunits.
AB - Nanoflow electrospray ionization has been used to introduce intact Escherichia
coli ribosomes into the ion source of a mass spectrometer. Mass spectra of
remarkable quality result from a partial, but selective, dissociation of the
particles within the mass spectrometer. Peaks in the spectra have been assigned
to individual ribosomal proteins and to noncovalent complexes of up to five
component proteins. The pattern of dissociation correlates strongly with
predicted features of ribosomal protein-protein and protein-RNA interactions. The
spectra allow the dynamics and state of folding of specific proteins to be
investigated in the context of the intact ribosome. This study demonstrates a
potentially general strategy to probe interactions within complex biological
assemblies.
PMID- 9636160
TI - Trans/cis (Z/E) photoisomerization of the chromophore of photoactive yellow
protein is not a prerequisite for the initiation of the photocycle of this
photoreceptor protein.
AB - The chromophore of photoactive yellow protein (PYP) (i.e., 4-hydroxycinnamic
acid) has been replaced by an analogue with a triple bond, rather than a double
bond (by using 4-hydroxyphenylpropiolic acid in the reconstitution, yielding
hybrid I) and by a "locked" chromophore (through reconstitution with 7
hydroxycoumarin-3-carboxylic acid, in which a covalent bridge is present across
the vinyl bond, resulting in hybrid II). These hybrids absorb maximally at 464
and 443 nm, respectively, which indicates that in both hybrids the deprotonated
chromophore does fit into the chromophore-binding pocket. Because the triple bond
cannot undergo cis/trans (or E/Z) photoisomerization and because of the presence
of the lock across the vinyl double bond in hybrid II, it was predicted that
these two hybrids would not be able to photocycle. Surprisingly, both are able.
We have demonstrated this ability by making use of transient absorption, low
temperature absorption, and Fourier-transform infrared (FTIR) spectroscopy. Both
hybrids, upon photoexcitation, display authentic photocycle signals in terms of a
red-shifted intermediate; hybrid I, in addition, goes through a blue-shifted-like
intermediate state, with very slow kinetics. We interpret these results as
further evidence that rotation of the carbonyl group of the thioester-linked
chromophore of PYP, proposed in a previous FTIR study and visualized in recent
time-resolved x-ray diffraction experiments, is of critical importance for
photoactivation of PYP.
PMID- 9636161
TI - Antigen binding forces of individually addressed single-chain Fv antibody
molecules.
AB - Antibody single-chain Fv fragment (scFv) molecules that are specific for
fluorescein have been engineered with a C-terminal cysteine for a directed
immobilization on a flat gold surface. Individual scFv molecules can be
identified by atomic force microscopy. For selected molecules the antigen binding
forces are then determined by using a tip modified with covalently immobilized
antigen. An scFv mutant of 12% lower free energy for ligand binding exhibits a
statistically significant 20% lower binding force. This strategy of covalent
immobilization and measuring well separated single molecules allows the
characterization of ligand binding forces in molecular repertoires at the single
molecule level and will provide a deeper insight into biorecognition processes.
PMID- 9636162
TI - Adjustment of conformational flexibility is a key event in the thermal adaptation
of proteins.
AB - 3-Isopropylmalate dehydrogenase (IPMDH, E.C. 1.1.1.85) from the thermophilic
bacterium Thermus thermophilus HB8 is homologous to IPMDH from the mesophilic
Escherichia coli, but has an approximately 17 degreesC higher melting
temperature. Its temperature optimum is 22-25 degreesC higher than that of the E.
coli enzyme; however, it is hardly active at room temperature. The increased
conformational rigidity required to stabilize the thermophilic enzyme against
heat denaturation might explain its different temperature-activity profile.
Hydrogen/deuterium exchange studies were performed on this thermophilic
mesophilic enzyme pair to compare their conformational flexibilities. It was
found that Th. thermophilus IPMDH is significantly more rigid at room temperature
than E. coli IPMDH, whereas the enzymes have nearly identical flexibilities under
their respective optimal working conditions, suggesting that evolutionary
adaptation tends to maintain a "corresponding state" regarding conformational
flexibility. These observations confirm that conformational fluctuations
necessary for catalytic function are restricted at room temperature in the
thermophilic enzyme, suggesting a close relationship between conformational
flexibility and enzyme function.
PMID- 9636163
TI - Structural basis of an embryonically lethal single Ala --> Thr mutation in the
vnd/NK-2 homeodomain.
AB - The structural and DNA binding behavior is described for an analog of the vnd/NK
2 homeodomain, which contains a single amino acid residue alanine to threonine
replacement in position 35 of the homeodomain. Multidimensional nuclear magnetic
resonance, circular dichroism, and electrophoretic gel retardation assays were
carried out on recombinant 80-aa residue proteins that encompass the wild-type
and mutant homeodomains. The mutant A35T vnd/NK-2 homeodomain is unable to adopt
a folded conformation free in solution at temperatures down to -5 degreesC in
contrast to the behavior of the corresponding wild-type vnd/NK-2 homeodomain,
which is folded into a functional three-dimensional structure below 25 degreesC.
The A35T vnd/NK-2 binds specifically to the vnd/NK-2 target DNA sequence, but
with an affinity that is 50-fold lower than that of the wild-type homeodomain.
Although the three-dimensional structure of the mutant A35T vnd/NK-2 in the DNA
bound state shows characteristic helix-turn-helix behavior similar to that of the
wild-type homeodomain, a notable structural deviation in the mutant A35T analog
is observed for the amide proton of leucine-40. The wild-type homeodomain forms
an unusual i,i-5 hydrogen bond with the backbone amide oxygen of residue 35. In
the A35T mutant this amide proton resonance is shifted upfield by 1.27 ppm
relative to the resonance frequency for the wild-type analog, thereby indicating
a significant alteration of this i,i-5 hydrogen bond.
PMID- 9636164
TI - Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal
tubular cells via the tyrosine kinase-Shc-Grb2-Sos pathway.
AB - In kidney epithelial cells, an angiotensin II (Ang II) type 2 receptor subtype
(AT2) is linked to a membrane-associated phospholipase A2 (PLA2) and the mitogen
activated protein kinase (MAPK) superfamily. However, the intervening steps in
this linkage have not been determined. The aim of this study was to determine
whether arachidonic acid mediates Ang II's effect on p21ras and if so, to
ascertain the signaling mechanism(s). We observed that Ang II activated p21ras
and that mepacrine, a phospholipase A2 inhibitor, blocked this effect. This
activation was also inhibited by PD123319, an AT2 receptor antagonist but not by
losartan, an AT1 receptor antagonist. Furthermore, Ang II caused rapid tyrosine
phosphorylation of Shc and its association with Grb2. Arachidonic acid and
linoleic acid mimicked Ang II-induced tyrosine phosphorylation of Shc and
activation of p21ras. Moreover, Ang II and arachidonic acid induced an
association between p21ras and Shc. We demonstrate that arachidonic acid mediates
linkage of a G protein-coupled receptor to p21ras via Shc tyrosine
phosphorylation and association with Grb2/Sos. These observations have important
implications for other G protein-coupled receptors linked to a variety of
phospholipases.
PMID- 9636165
TI - Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro.
AB - The proinflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)
promote HIV type 1 viral replication in vitro. In the present studies, HIV
production was increased in the macrophagic U1 cell line expressing the HIV
genome after exposure to IL-1beta, osmotic stress, or surface adhesion,
suggesting a confluence of signaling pathways for proinflammatory cytokines and
cell stressors. The p38 mitogen-activated protein kinase (MAPK) mediates both
cytokine and stress responses; thus the role of this kinase in HIV production was
investigated. HIV production as measured by p24 antigen correlated with changes
in the expression of a specific (non-alpha) isoform of p38 MAPK. In the presence
of a specific p38 MAPK inhibitor (p38 inh), IL-1beta-induced HIV production was
suppressed by more than 90% and IL-1beta-induced IL-8 production was suppressed
completely, both with IC50 of 0.01 microM. p38 inhibition blocked cell-associated
p24 antigen and secreted virus to a similar extent. The p38 inh also decreased
constitutive HIV production in freshly infected peripheral blood mononuclear
cells by up to 50% (P < 0.05). Interruption of p38 MAPK activity represents a
viable target for inhibition of HIV.
PMID- 9636166
TI - A member of the Ran-binding protein family, Yrb2p, is involved in nuclear protein
export.
AB - Yeast cells mutated in YRB2, which encodes a nuclear protein with similarity to
other Ran-binding proteins, fail to export nuclear export signal (NES)-containing
proteins including HIV Rev out of the nucleus. Unlike Xpo1p/Crm1p/exportin, an
NES receptor, Yrb2p does not shuttle between the nucleus and the cytoplasm but
instead remains inside the nucleus. However, by both biochemical and genetic
criteria, Yrb2p interacts with Xpo1p and not with other members of the
importin/karyopherin beta superfamily. Moreover, the Yrb2p region containing
nucleoporin-like FG repeats is important for NES-mediated protein export. Taken
together, these data suggest that Yrb2p acts inside the nucleus to mediate the
action of Xpo1p in at least one of several nuclear export pathways.
PMID- 9636167
TI - Resistance gene N-mediated de novo synthesis and activation of a tobacco mitogen
activated protein kinase by tobacco mosaic virus infection.
AB - Salicylic acid-induced protein kinase (SIPK) and wounding-induced protein kinase
(WIPK), two distinct members of the mitogen-activated protein (MAP) kinase
family, are activated in tobacco resisting infection by tobacco mosaic virus
(TMV). WIPK activation by TMV depends on the disease-resistance gene N because
infection of susceptible tobacco not carrying the N gene failed to activate WIPK.
Activation of WIPK required not only posttranslational phosphorylation but also a
preceding rise in its mRNA and de novo synthesis of WIPK protein. The induction
by TMV of WIPK mRNA and protein also occurred systemically. Its activation at the
mRNA, protein, and enzyme levels was independent of salicylic acid. The
regulation of WIPK at multiple levels by an N gene-mediated signal(s) suggests
that this MAP kinase may be an important component upstream of salicylic acid in
the signal-transduction pathway(s) leading to local and systemic resistance to
TMV.
PMID- 9636168
TI - Dissociation of cytokine-induced phosphorylation of Bad and activation of
PKB/akt: involvement of MEK upstream of Bad phosphorylation.
AB - The phosphatidylinositol 3-kinase (PI3K)-signaling pathway has emerged as an
important component of cytokine-mediated survival of hemopoietic cells. Recently,
the protein kinase PKB/akt (referred to here as PKB) has been identified as a
downstream target of PI3K necessary for survival. PKB has also been implicated in
the phosphorylation of Bad, potentially linking the survival effects of cytokines
with the Bcl-2 family. We have shown that granulocyte/macrophage colony
stimulating factor (GM-CSF) maintains survival in the absence of PI3K activity,
and we now show that when PKB activation is also completely blocked, GM-CSF is
still able to stimulate phosphorylation of Bad. Interleukin 3 (IL-3), on the
other hand, requires PI3K for survival, and blocking PI3K partially inhibited Bad
phosphorylation. IL-4, unique among the cytokines in that it lacks the ability to
activate the p21ras-mitogen-activated protein kinase (MAPK) cascade, was found to
activate PKB and promote cell survival, but it did not stimulate Bad
phosphorylation. Finally, although our data suggest that the MAPK pathway is not
required for inhibition of apoptosis, we provide evidence that phosphorylation of
Bad may be occurring via a MAPK/ERK kinase (MEK)-dependent pathway. Together,
these results demonstrate that although PI3K may contribute to phosphorylation of
Bad in some instances, there is at least one other PI3K-independent pathway
involved, possibly via activation of MEK. Our data also suggest that although
phosphorylation of Bad may be one means by which cytokines can inhibit apoptosis,
it may be neither sufficient nor necessary for the survival effect.
PMID- 9636169
TI - Protein kinase mutants of human ATR increase sensitivity to UV and ionizing
radiation and abrogate cell cycle checkpoint control.
AB - In fission yeast, the rad3 gene product plays a critical role in sensing DNA
structure defects and activating damage response pathways. A structural homologue
of rad3 in humans (ATR) has been identified based on sequence similarity in the
protein kinase domain. General information regarding ATR expression, protein
kinase activity, and cellular localization is known, but its function in human
cells remains undetermined. In the current study, the ATR protein was examined by
gel filtration of protein extracts and was found to exist predominantly as part
of a large protein complex. A kinase-inactivated form of the ATR gene was
prepared by site-directed mutagenesis and was used in transfection experiments to
probe the function of this complex. Introduction of this kinase-dead ATR into a
normal fibroblast cell line, an ATM-deficient fibroblast line derived from a
patient with ataxia-telangiectasia, or a p53 mutant cell line all resulted in
significant losses in cell viability. Clones expressing the kinase-dead ATR
displayed increased sensitivity to x-rays and UV and a loss of checkpoint
control. We conclude that ATR functions as a critical part of a protein complex
that mediates responses to ionizing and UV radiation in human cells. These
responses include effects on cell viability and cell cycle checkpoint control.
PMID- 9636170
TI - Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with
SKP1 and an F-box protein.
AB - The SCF ubiquitin ligase complex of budding yeast triggers DNA replication by
catalyzing ubiquitination of the S phase cyclin-dependent kinase inhibitor SIC1.
SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein
CDC4-that are conserved from yeast to humans. As part of an effort to identify
components and substrates of a putative human SCF complex, we isolated hSKP1 in a
two-hybrid screen with hCUL1, the closest human homologue of CDC53. Here, we show
that hCUL1 associates with hSKP1 in vivo and directly interacts with both hSKP1
and the human F-box protein SKP2 in vitro, forming an SCF-like particle.
Moreover, hCUL1 complements the growth defect of yeast cdc53(ts) mutants,
associates with ubiquitination-promoting activity in human cell extracts, and can
assemble into functional, chimeric ubiquitin ligase complexes with yeast SCF
components. Taken together, these data suggest that hCUL1 functions as part of an
SCF ubiquitin ligase complex in human cells. Further application of biochemical
assays similar to those described here can now be used to identify
regulators/components of hCUL1-based SCF complexes, to determine whether the
hCUL2-hCUL5 proteins also are components of ubiquitin ligase complexes in human
cells, and to screen for chemical compounds that modulate the activities of the
hSKP1 and hCUL1 proteins.
PMID- 9636171
TI - Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase.
AB - The ubiquitously expressed nonreceptor tyrosine kinase c-Abl contains three
nuclear localization signals, however, it is found in both the nucleus and the
cytoplasm of proliferating fibroblasts. A rapid and transient loss of c-Abl from
the nucleus is observed upon the initial adhesion of fibroblasts onto a
fibronectin matrix, suggesting the possibility of nuclear export [Lewis, J.,
Baskaran, R. , Taagepera, S., Schwartz, M. & Wang, J. (1996) Proc. Natl. Acad.
Sci. USA 93, 15174-15179]. Here we show that the C terminus of c-Abl does indeed
contain a functional nuclear export signal (NES) with the characteristic leucine
rich motif. The c-Abl NES can functionally complement an NES-defective HIV Rev
protein (RevDelta3NI) and can mediate the nuclear export of glutathione-S
transferase. The c-Abl NES function is sensitive to the nuclear export inhibitor
leptomycin B. Mutation of a single leucine (L1064A) in the c-Abl NES abrogates
export function. The NES-mutated c-Abl, termed c-Abl NES(-), is localized
exclusively to the nucleus. Treatment of cells with leptomycin B also leads to
the nuclear accumulation of wild-type c-Abl protein. The c-Abl NES(-) is not lost
from the nucleus when detached fibroblasts are replated onto fibronectin matrix.
Taken together, these results demonstrate that c-Abl shuttles continuously
between the nucleus and the cytoplasm and that the rate of nuclear import and
export can be modulated by the adherence status of fibroblastic cells.
PMID- 9636172
TI - A chloroplast processing enzyme functions as the general stromal processing
peptidase.
AB - A highly specific stromal processing activity is thought to cleave a large
diversity of precursors targeted to the chloroplast, removing an N-terminal
transit peptide. The identity of this key component of the import machinery has
not been unequivocally established. We have previously characterized a
chloroplast processing enzyme (CPE) that cleaves the precursor of the light
harvesting chlorophyll a/b binding protein of photosystem II (LHCPII). Here we
report the overexpression of active CPE in Escherichia coli. Examination of the
recombinant enzyme in vitro revealed that it cleaves not only preLHCPII, but also
the precursors for an array of proteins essential for different reactions and
destined for different compartments of the organelle. CPE also processes its own
precursor in trans. Neither the recombinant CPE nor the native CPE of
chloroplasts process a preLHCPII mutant with an altered cleavage site
demonstrating that both forms of the enzyme are sensitive to the same structural
modification of the substrate. The transit peptide of the precursor of ferredoxin
is released by a single cleavage event and found intact after processing by
recombinant CPE and a chloroplast extract as well. These results provide the
first direct demonstration that CPE is the general stromal processing peptidase
that acts as an endopeptidase. Significantly, recombinant CPE cleaves in the
absence of other chloroplast proteins, and this activity depends on metal
cations, such as zinc.
PMID- 9636173
TI - Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec
2) on B lymphocytes.
AB - CD22 is a B cell-restricted glycoprotein involved in signal transduction and
modulation of cellular activation. It is also an I-type lectin (now designated
Siglec-2), whose extracellular domain can specifically recognize alpha2-6-linked
sialic acid (Sia) residues. This activity is postulated to mediate intercellular
adhesion and/or to act as a coreceptor in antigen-induced B cell activation.
However, studies with recombinant CD22 indicate that the lectin function can be
inactivated by expression of alpha2-6-linked Sia residues on the same cell
surface. To explore whether this masking phenomenon affects native CD22 on B
cells, we first developed a probe to detect the lectin activity of recombinant
CD22 expressed on Chinese hamster ovary cells (which have no endogenous alpha2-6
linked Sia residues). This probe is inactive against CD22-positive B lymphoma
cells and Epstein-Barr virus-transformed lymphoblasts which express high levels
of alpha2-6-linked Sia residues. Enzymatic desialylation unmasks the CD22 lectin
activity, indicating that endogenous Sia residues block the CD22 lectin-binding
site. Truncation of the side chains of cell surface Sia residues by mild
periodate oxidation (known to abrogate Sia recognition by CD22) also had this
unmasking effect, indicating that the effects of desialylation are not due to a
loss of negative charge. Normal resting B cells from human peripheral blood gave
similar findings. However, the lectin is partially unmasked during in vitro
activation of these cells. Thus, the lectin activity of CD22 is restricted by
endogenous sialylation in resting B cells and may be transiently unmasked during
in vivo activation, perhaps to modulate intercellular or intracellular
interactions at this critical stage in the humoral response.
PMID- 9636174
TI - Mitogenic and oncogenic properties of the small G protein Rap1b.
AB - It has been widely reported that the small GTP-binding protein Rap1 has an anti
Ras and anti-mitogenic activity. Thus, it is generally accepted that a normal
physiological role of Rap1 proteins is to antagonize Ras mitogenic signals,
presumably by forming nonproductive complexes with proteins that are typically
effectors or modulators of Ras. Rap1 is activated by signals that raise
intracellular levels of cAMP, a molecule that has long been known to exert both
inhibitory and stimulatory effects on cell growth. We have now tested the
intriguing hypothesis that Rap1 could have mitogenic effects in systems in which
cAMP stimulates cell proliferation. The result of experiments addressing this
possibility revealed that Rap1 has full oncogenic potential. Expression of Rap1
in these cells results in a decreased doubling time, an increased saturation
density, and an unusual anchorage-dependent morphological transformation. Most
significantly, however, Rap1-expressing cells formed tumors when injected into
nude mice. Thus, we propose that the view that holds Rap1 as an antimitogenic
protein should be restricted and conclude that Rap1 is a conditional oncoprotein.
PMID- 9636175
TI - Phosphorylation of histone H3 at serine 10 is correlated with chromosome
condensation during mitosis and meiosis in Tetrahymena.
AB - H3 phosphorylation has been correlated with mitosis temporally in mammalian cells
and spatially in ciliated protozoa. In logarithmically growing Tetrahymena
thermophila cells, for example, H3 phosphorylation can be detected in germline
micronuclei that divide mitotically but not in somatic macronuclei that divide
amitotically. Here, we demonstrate that micronuclear H3 phosphorylation occurs at
a single site (Ser-10) in the amino-terminal domain of histone H3, the same site
phosphorylated during mitosis in mammalian cells. Using an antibody specific for
Ser-10 phosphorylated H3, we show that, in Tetrahymena, this modification is
correlated with mitotic and meiotic divisions of micronuclei in a fashion that
closely coincides with chromosome condensation. Our data suggest that H3
phosphorylation at Ser-10 is a highly conserved event among eukaryotes and is
likely involved in both mitotic and meiotic chromosome condensation.
PMID- 9636176
TI - A phenotype-based screen for embryonic lethal mutations in the mouse.
AB - The genetic pathways that control development of the early mammalian embryo have
remained poorly understood, in part because the systematic mutant screens that
have been so successful in the identification of genes and pathways that direct
embryonic development in Drosophila, Caenorhabditis elegans, and zebrafish have
not been applied to mammalian embryogenesis. Here we demonstrate that chemical
mutagenesis with ethylnitrosourea can be combined with the resources of mouse
genomics to identify new genes that are essential for mammalian embryogenesis. A
pilot screen for abnormal morphological phenotypes of midgestation embryos
identified five mutant lines; the phenotypes of four of the lines are caused by
recessive traits that map to single regions of the genome. Three mutant lines
display defects in neural tube closure: one is caused by an allele of the open
brain (opb) locus, one defines a previously unknown locus, and one has a complex
genetic basis. Two mutations produce novel early phenotypes and map to regions of
the genome not previously implicated in embryonic patterning.
PMID- 9636177
TI - Retardation of skeletal development and cervical abnormalities in transgenic mice
expressing a dominant-negative retinoic acid receptor in chondrogenic cells.
AB - Skeletal formation is a fundamental element of body patterning and is strictly
regulated both temporally and spatially by a variety of molecules. Among these,
retinoic acid (RA) has been shown to be involved in normal skeletal development.
However, its pleiotropic effects have caused difficulty in identifying its
crucial target cells and molecular mechanisms for each effect. Development of
cartilage primordia is an important process in defining the skeletal structures.
To address the role of RA in skeletal formation, we have generated mice
expressing a dominant-negative retinoic acid receptor (RAR) in chondrogenic cells
by using the type II collagen alpha1 promoter, and we have analyzed their
phenotypes. These mice exhibited small cartilage primordia during development and
retarded skeletal formation in both embryonic and postnatal periods. They also
showed selective degeneration in their cervical vertebrae combined with homeotic
transformations, but not in their extremities. The cervical phenotypes are
reminiscent of phenotypes involving homeobox genes. We found that the expression
of Hoxa-4 was indeed reduced in the cartilage primordia of cervical vertebrae of
embryonic day 12.5 embryos. These observations demonstrate that endogenous RA
acts directly on chondrogenic cells to promote skeletal growth in both embryonic
and growing periods, and it regulates the proper formation of cervical vertebrae.
Furthermore, RA apparently specifies the identities of the cervical vertebrae
through the regulation of homeobox genes in the chondrogenic cells. Great
similarities of the phenotypes between our mice and reported RAR knockout mice
revealed that chondrogenic cells are a principal RA target during complex
cascades of skeletal development.
PMID- 9636178
TI - Higher temporal variability of forest breeding bird communities in fragmented
landscapes.
AB - Understanding the relationship between animal community dynamics and landscape
structure has become a priority for biodiversity conservation. In particular,
predicting the effects of habitat destruction that confine species to networks of
small patches is an important prerequisite to conservation plan development.
Theoretical models that predict the occurrence of species in fragmented
landscapes, and relationships between stability and diversity do exist. However,
reliable empirical investigations of the dynamics of biodiversity have been
prevented by differences in species detection probabilities among landscapes.
Using long-term data sampled at a large spatial scale in conjunction with a
capture-recapture approach, we developed estimates of parameters of community
changes over a 22-year period for forest breeding birds in selected areas of the
eastern United States. We show that forest fragmentation was associated not only
with a reduced number of forest bird species, but also with increased temporal
variability in the number of species. This higher temporal variability was
associated with higher local extinction and turnover rates. These results have
major conservation implications. Moreover, the approach used provides a practical
tool for the study of the dynamics of biodiversity.
PMID- 9636179
TI - Identification of novel susceptibility loci for inflammatory bowel disease on
chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1.
AB - The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative
colitis (UC), are chronic, frequently disabling diseases of the intestines.
Segregation analyses, twin concordance, and ethnic differences in familial risks
have established that CD and UC are complex, non-Mendelian, related genetic
disorders. We performed a genome-wide screen using 377 autosomal markers, on 297
CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed
evidence for linkage at 3q for all families (multipoint logarithm of the odds
score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non
Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p
(MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed
families (containing one member with CD and another with UC), evidence for
linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially
among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping
IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(
3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however,
positive MLod scores were observed over a very broad region of chromosome 16.
Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed.
Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence
for linkage. This screen provides strong evidence that there are several major
susceptibility loci contributing to the genetic risk for CD and UC.
PMID- 9636180
TI - Transdominant genetic analysis of a growth control pathway.
AB - Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA
libraries to cause mutant phenocopies may facilitate genetic analysis in
traditionally nongenetic organisms. We performed a selection for random short
peptides and larger protein fragments (collectively termed "perturbagens") that
inhibit the yeast pheromone response pathway. Peptide and protein fragment
perturbagens that permit cell division in the presence of pheromone were
recovered. Two perturbagens were derived from proteins required for pheromone
response, and an additional two were derived from proteins that may negatively
influence the pheromone response pathway. Furthermore, three known components of
the pathway were identified as probable perturbagen targets based on physical
interaction assays. Thus, by selection for transdominant inhibitors of pheromone
response, multiple pathway components were identified either directly as gene
fragments or indirectly as the likely targets of specific perturbagens. These
results, combined with the results of previous work [Holzmayer, T. A., Pestov, D.
G. & Roninson, I. B. (1992) Nucl. Acids. Res. 20, 711-717; Whiteway, M., Dignard,
D. & Thomas, D. Y. (1992) Proc. Natl. Acad. Sci. USA 89, 9410-9414; and Gudkov,
A. V., Kazarov, A. R., Thimmapaya, R., Axenovich, S. A., Mazo, I. A. & Roninson,
I. B. (1994) Proc. Natl. Acad. Sci. USA 91, 3744-3748], suggest that
transdominant genetic analysis of the type described here will be broadly
applicable.
PMID- 9636181
TI - Computerized polymorphic marker identification: experimental validation and a
predicted human polymorphism catalog.
AB - A computational system for the prediction of polymorphic loci directly and
efficiently from human genomic sequence was developed and verified. A suite of
programs, collectively called POMPOUS (polymorphic marker prediction of
ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up
to 250 mers, scores them according to predicted level of polymorphism, and
designs appropriate flanking primers for PCR amplification. This approach was
validated on an approximately 750-kilobase region of human chromosome 3p21.3,
involved in lung and breast carcinoma homozygous deletions. Target DNA from 36
paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for
33 loci predicted by POMPOUS to be variable in repeat size. We found that among
those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci
were polymorphic with an average heterozygosity of 0.42. Allele loss in this
region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS
provides the genetic researcher with an additional tool for the rapid and
efficient identification of polymorphic markers, and through a World Wide Web
site, investigators can use POMPOUS to identify polymorphic markers for their
research. A catalog of 13,261 potential polymorphic markers and associated primer
sets has been created from the analysis of 141,779,504 base pairs of human
genomic sequence in GenBank. This data is available on our Web site
(pompous.swmed.edu) and will be updated periodically as GenBank is expanded and
algorithm accuracy is improved.
PMID- 9636182
TI - The lepidopteran transposon vector, piggyBac, mediates germ-line transformation
in the Mediterranean fruit fly.
AB - The piggyBac (IFP2) short inverted terminal repeat transposable element from the
cabbage looper Trichoplusia ni was tested for gene transfer vector function as
part of a bipartite vector-helper system in the Mediterranean fruit fly Ceratitis
capitata. A piggyBac vector marked with the medfly white gene was tested with a
normally regulated piggyBac transposase helper at two different concentrations in
a white eye host strain. Both experiments yielded transformants at an approximate
frequency of 3-5%, with a total of six lines isolated having pigmented eyes with
various levels of coloration. G1 transformant siblings from each line shared at
least one common integration, with several sublines having an additional second
integration. For the first transformant line isolated, two integrations were
determined to be stable for 15 generations. For five of the lines, a piggyBac
mediated transposition was verified by sequencing the insertion site junctions
isolated by inverse PCR that identified a characteristic piggyBac TTAA target
site duplication. The efficient and stable transformation of the medfly with a
lepidopteran vector represents transposon function over a relatively large
evolutionary distance and suggests that the piggyBac system will be functional in
a broad range of insects.
PMID- 9636183
TI - Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and
myotonic dystrophy kinase, is required for maintenance of cell polarity and
coordinates cell morphogenesis with the cell cycle.
AB - The molecular mechanisms that coordinate cell morphogenesis with the cell cycle
remain largely unknown. We have investigated this process in fission yeast where
changes in polarized cell growth are coupled with cell cycle progression. The
orb6 gene is required during interphase to maintain cell polarity and encodes a
serine/threonine protein kinase, belonging to the myotonic dystrophy
kinase/cot1/warts family. A decrease in Orb6 protein levels leads to loss of
polarized cell shape and to mitotic advance, whereas an increase in Orb6 levels
maintains polarized growth and delays mitosis by affecting the p34(cdc2) mitotic
kinase. Thus the Orb6 protein kinase coordinates maintenance of cell polarity
during interphase with the onset of mitosis. orb6 interacts genetically with
orb2, which encodes the Pak1/Shk1 protein kinase, a component of the Ras1 and
Cdc42-dependent signaling pathway. Our results suggest that Orb6 may act
downstream of Pak1/Shk1, forming part of a pathway coordinating cell
morphogenesis with progression through the cell cycle.
PMID- 9636184
TI - Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric
heterochromatin of Drosophila melanogaster polytene chromosomes.
AB - A genetic locus suppressing DNA underreplication in intercalary heterochromatin
(IH) and pericentric heterochromatin (PH) of the polytene chromosomes of
Drosophila melanogaster salivary glands, has been described. Found in the
In(1)scV2 strain, the mutation, designated as Su(UR)ES, was located on chromosome
3L at position 34. 8 and cytologically mapped to region 68A3-B4. A cytological
phenotype was observed in the salivary gland chromosomes of larvae homozygous and
hemizygous for Su(UR)ES: (i) in the IH regions, that normally are incompletely
polytenized and so they often break to form "weak points," underreplication is
suppressed, breaks and ectopic contacts disappear; (ii) the degree of
polytenization in PH grows higher. That is why the regions in chromosome arm
basements, normally beta-heterochromatic, acquire a distinct banding pattern, i.
e., become euchromatic by morphological criteria; (iii) an additional bulk of
polytenized material arises between the arms of chromosome 3 to form a fragment
with a typical banding pattern. Chromosome 2 PH reveals additional alpha
heterochromatin. Su(UR)ES does not affect the viability, fertility, or
morphological characters of the imago, and has semidominant expression in the
heterozygote and distinct maternal effect. The results obtained provide evidence
that the processes leading to DNA underreplication in IH and PH are affected by
the same genetic mechanism.
PMID- 9636185
TI - Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role
for autoantibodies in the loss of secretory function of exocrine tissues in
Sjogren's syndrome.
AB - The NOD (nonobese diabetic) mouse has been studied as an animal model for
autoimmune insulin-dependent diabetes and Sjogren's syndrome. NOD.Igmu null mice,
which lack functional B lymphocytes, develop progressive histopathologic lesions
of the submandibular and lachrymal glands similar to NOD mice, but in the absence
of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in
salivary and lachrymal tissues, NOD.Igmu null mice fail to lose secretory
function as determined by stimulation of the muscarinic/cholinergic receptor by
the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating
exocrine dryness. Infusion of purified serum IgG or F(ab')2 fragments from
parental NOD mice or human primary Sjogren's syndrome patients, but not serum IgG
from healthy controls, alters stimulated saliva production, an observation
consistent with antibody binding to neural receptors. Furthermore, human patient
IgG fractions competitively inhibited the binding of the muscarinic receptor
agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This
autoantibody activity is lost after preadsorption with intact salivary cells.
These findings indicate that autoantibodies play an important part in the
functional impairment of secretory processes seen in connection with the
autoimmune exocrinopathy of Sjogren's syndrome.
PMID- 9636186
TI - Extracellular enveloped vaccinia virus is resistant to complement because of
incorporation of host complement control proteins into its envelope.
AB - Vaccinia virus (VV) produces two antigenically and structurally distinct
infectious virions, intracellular mature virus (IMV) and extracellular enveloped
virus (EEV). Here we have investigated the resistance of EEV and IMV to
neutralization by complement in the absence of immune antibodies. When EEV is
challenged with complement from the same species as the cells used to grow the
virus, EEV is resistant to neutralization by complement, whereas IMV is not. EEV
resistance was not a result of EEV protein B5R, despite its similarity to
proteins of the regulators of complement activation (RCA) family, or to any of
the other EEV proteins tested (A34R, A36R, and A56R gene products). EEV was
sensitive to complement when the virus was grown in one species and challenged
with complement from a different species, suggesting that complement resistance
might be mediated by host RCA incorporated into the EEV outer envelope. This
hypothesis was confirmed by several observations: (i) immunoblot analysis
revealed that cellular membrane proteins CD46, CD55, CD59, CD71, CD81, and major
histocompatibility complex class I antigen were detected in purified EEV but not
IMV; (ii) immunoelectron microscopy revealed cellular RCA on the surface of EEV
retained on the cell surface; and (iii) EEV derived from rat cells expressing the
human RCA CD55 or CD55 and CD59 were more resistant to human complement than EEV
derived from control rat cells that expressed neither CD55 nor CD59. These data
justify further analysis of the roles of these (and possible other) cellular
proteins in EEV biology.
PMID- 9636187
TI - Tropomyosin implicated in host protective responses to microfilariae in
onchocerciasis.
AB - A cDNA from adult female Onchocerca volvulus encoding the C-terminal portion of a
tropomyosin isoform (termed MOv-14) has been shown previously to confer
protective immunity in rodent models of onchocerciasis. The full-length sequence
(designated Ov-tmy-1) obtained by PCR amplification, codes for a protein of 33
kDa and shares 91% identity with tropomyosins from other nematodes, falling to
57% identity with human alpha-tropomyosin. Ov-TMY-1 migrates with an apparent
molecular mass of 42 kDa on SDS/PAGE and is present in all life-cycle stages, as
determined by immunoblotting. Immunogold electron microscopy identified antigenic
sites within muscle blocks and the cuticle of microfilariae and infective larvae.
Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable
protection against microfilariae conferred by vaccination with a PBS-soluble
parasite extract. In contrast, little or no MOv14-specific antibody was present
in mice inoculated with live microfilariae, in which resistance is mediated by
antibody-independent mechanisms. In human infections, there was an inverse
correlation between anti-tropomyosin IgG levels and densities of microfilariae in
the skin. Seropositivity varied with the relative endemicity of infection. An
immunodominant B cell epitope within Ov-TMY-1 (AQLLAEEADRKYD) was mapped to the N
terminus of the MOv14 protein by using sera from protectively vaccinated mice.
Intriguingly, the sequence coincides with an IgE-binding epitope within shrimp
tropomyosin, believed to be responsible for hypersensitivity in individuals
exhibiting allergy to shellfish. IgG and IgE antibodies reacting with the O.
volvulus epitope were detected in human infections. It is concluded that antibody
responses to tropomyosin may be important in limiting microfilarial densities in
a proportion of individuals with onchocerciasis and have the potential to mediate
hypersensitivity reactions to dead microfilariae, raising the possibility of a
link with the immunopathology of infection.
PMID- 9636188
TI - Demonstration of an interferon gamma-dependent tumor surveillance system in
immunocompetent mice.
AB - This study demonstrates that endogenously produced interferon gamma (IFN-gamma)
forms the basis of a tumor surveillance system that controls development of both
chemically induced and spontaneously arising tumors in mice. Compared with wild
type mice, mice lacking sensitivity to either IFN-gamma (i.e., IFN-gamma receptor
deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed
tumors more rapidly and with greater frequency when challenged with different
doses of the chemical carcinogen methylcholanthrene. In addition, IFN-gamma
insensitive mice developed tumors more rapidly than wild-type mice when bred onto
a background deficient in the p53 tumor-suppressor gene. IFN-gamma-insensitive
p53(-/-) mice also developed a broader spectrum of tumors compared with mice
lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN
gamma-insensitive mice, we found IFN-gamma's actions to be mediated at least
partly through its direct effects on the tumor cell leading to enhanced tumor
cell immunogenicity. The importance and generality of this system is evidenced by
the finding that certain types of human tumors become selectively unresponsive to
IFN-gamma. Thus, IFN-gamma forms the basis of an extrinsic tumor-suppressor
mechanism in immunocompetent hosts.
PMID- 9636189
TI - Optimal selectin-mediated rolling of leukocytes during inflammation in vivo
requires intercellular adhesion molecule-1 expression.
AB - Leukocyte interactions with vascular endothelium during inflammation occur
through discrete steps involving selectin-mediated leukocyte rolling and
subsequent firm adhesion mediated by members of the integrin and Ig families of
adhesion molecules. To identify functional synergy between selectin and Ig family
members, mice deficient in both L-selectin and intercellular adhesion molecule 1
(ICAM-1) were generated. Leukocyte rolling velocities in cremaster muscle venules
were increased significantly in ICAM-1-deficient mice during both trauma- and
tumor necrosis factor alpha-induced inflammation, but rolling leukocyte flux was
not reduced. Elimination of ICAM-1 expression in L-selectin-deficient mice
resulted in a sharp reduction in the flux of rolling leukocytes during tumor
necrosis factor alpha-induced inflammation. The observed differences in leukocyte
rolling behavior demonstrated that ICAM-1 expression was required for optimal P-
and L-selectin-mediated rolling. Increased leukocyte rolling velocities
presumably translated into decreased tissue emigration because circulating
neutrophil, monocyte, and lymphocyte numbers were increased markedly in L
selectin/ICAM-1-deficient mice. Furthermore, neutrophil emigration during acute
peritonitis was reduced by 80% in the double-deficient mice compared with either
L-selectin or ICAM-1-deficient mice. Thus, members of the selectin and Ig
families function synergistically to mediate optimal leukocyte rolling in vivo,
which is essential for the generation of effective inflammatory responses.
PMID- 9636190
TI - Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific
CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal
fluid from HAM/TSP patients.
AB - Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic
paraparesis is a demyelinating inflammatory neurologic disease associated with
HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated
from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig
complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral
blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1
associated myelopathy/tropic spastic paraparesis patients carried a significant
number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19
peptide in their peripheral blood, which were not found in healthy controls.
Simultaneous comparison of peripheral blood and cerebrospinal fluid from one
patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal
fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells
were seen consistently over a 9-yr time course in one patient as far as 19 yrs
after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19
specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression
patterns of activation markers, intracellular TNF-alpha and gamma-interferon
depending on the severity of the disease. Thus, visualization of antigen-specific
T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated,
persist during the chronic phase of the disease, and accumulate in cerebrospinal
fluid, showing their pivotal role in the pathogenesis of this neurologic disease.
PMID- 9636191
TI - Definition of MHC and T cell receptor contacts in the HLA-DR4restricted
immunodominant epitope in type II collagen and characterization of collagen
induced arthritis in HLA-DR4 and human CD4 transgenic mice.
AB - Rheumatoid arthritis (RA) is an autoimmune disease associated with the HLA-DR4
and DR1 alleles. The target autoantigen(s) in RA is unknown, but type II collagen
(CII) is a candidate, and the DR4- and DR1-restricted immunodominant T cell
epitope in this protein corresponds to amino acids 261-273 (CII 261-273). We have
defined MHC and T cell receptor contacts in CII 261-273 and provide strong
evidence that this peptide corresponds to the peptide binding specificity
previously found for RA-associated DR molecules. Moreover, we demonstrate that
HLA-DR4 and human CD4 transgenic mice homozygous for the I-Abbeta0 mutation are
highly susceptible to collagen-induced arthritis and describe the clinical course
and histopathological changes in the affected joints.
PMID- 9636192
TI - Resistance to endotoxic shock and reduced neutrophil migration in mice deficient
for the Src-family kinases Hck and Fgr.
AB - Signal transduction through the leukocyte integrins is required for the processes
of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory
reactions. Neutrophils isolated from knockout mice that are deficient in the
expression of p59/61(hck) (Hck) and p58(c-fgr) (Fgr), members of the Src-family
of protein tyrosine kinases, have been shown to be defective in adhesion mediated
activation. Cells from these animals have impaired induction of respiratory burst
and granule secretion following plating on surfaces that crosslink beta2 and
beta3 integrins. To determine if the defective function of hck-/-fgr-/-
neutrophils observed in vitro also results in impaired inflammatory responses in
vivo, we examined responses induced by lipopolysaccharide (LPS) injection in
these animals. The hck-/-fgr-/- mice showed marked resistance to the lethal
effects of high-dose LPS injection despite the fact that high levels of serum
tumor necrosis factor alpha and interleukin 1alpha were detected. Serum chemistry
analysis revealed a marked reduction in liver and renal damage in mutant mice
treated with LPS, whereas blood counts showed a marked neutrophilia that was not
seen in wild-type animals. Direct examination of liver sections from mutant mice
revealed reduced neutrophil migration into the tissue. These data demonstrate
that defective integrin signaling in neutrophils, caused by loss of Hck and Fgr
tyrosine kinase activity, results in impaired inflammation-dependent tissue
injury in vivo.
PMID- 9636193
TI - Low-dose expression of a human apolipoprotein E transgene in macrophages restores
cholesterol efflux capacity of apolipoprotein E-deficient mouse plasma.
AB - Apolipoprotein E- (apoE) deficient (E-/-) mice develop severe hyperlipidemia and
diffuse atherosclerosis. Low-dose expression of a human apoE3 transgene in
macrophages of apoE-deficient mice (E-/-hTgE+/0), which results in about 5% of
wild-type apoE plasma levels, did not correct hyperlipidemia but significantly
reduced the extent of atherosclerotic lesions. To investigate the contribution of
apoE to reverse cholesterol transport, we compared plasmas of wild-type (E+/+), E
/-, and E-/-hTgE+/0 mice for the appearance of apoE-containing lipoproteins by
electrophoresis and their capacity to take up and esterify 3H-labeled cholesterol
from radiolabeled fibroblasts or J774 macrophages. Wild-type plasma displayed
lipoproteins containing apoE that were the size of high density lipoprotein and
that had either electrophoretic alpha or gamma mobilities. Similar particles were
also present in E-/-hTgE+/0 plasma. Depending on incubation time, E-/- plasma
released 48-74% less 3H-labeled cholesterol from fibroblasts than E+/+ plasma,
whereas cholesterol efflux into E-/-hTgE+/0 plasma was only 11-25% lower than
into E+/+ plasma. E-/-hTgE+/0 plasma also released 10% more 3H-labeled
cholesterol from radiolabeled J774 macrophages than E-/- plasma. E+/+ and E-/
hTgE+/0 plasma each esterified significantly more cell-derived 3H-labeled
cholesterol than E-/- plasma. Moreover, E-/- plasma accumulated much smaller
proportions of fibroblast-derived 3H-labeled cholesterol in fractions with
electrophoretic gamma and alpha mobility than E+/+ and E-/-hTgE+/0 plasma. Thus,
low-dose expression of apoE in macrophages nearly restored the cholesterol efflux
capacity of apoE-deficient plasma through the formation of apoE-containing
particles, which efficiently take up cell-derived cholesterol, and through the
increase of cholesterol esterification activity. Thus, macrophage-derived apoE
may protect against atherosclerosis by increasing cholesterol efflux from
arterial wall cells.
PMID- 9636194
TI - Tissue factor gene expression in the adipose tissues of obese mice.
AB - Altered expression of proteins of the fibrinolytic and coagulation cascades in
obesity may contribute to the cardiovascular risk associated with this condition.
We previously reported that plasminogen activator inhibitor 1 (PAI-1) is
dramatically up-regulated in the plasma and adipose tissues of genetically obese
mice. This change may disturb normal hemostatic balance and create a severe
hypofibrinolytic state. Here we show that tissue factor (TF) gene expression also
is significantly elevated in the epididymal and subcutaneous fat pads from ob/ob
mice compared with their lean counterparts, and that its level of expression in
obese mice increases with age and the degree of obesity. Cell fractionation and
in situ hybridization analysis of adipose tissues indicate that TF mRNA is
increased in adipocytes and in unidentified stromal vascular cells. Transforming
growth factor beta (TGF-beta) is known to be elevated in the adipose tissue of
obese mice, and administration of TGF-beta increased TF mRNA expression in
adipocytes in vivo and in vitro. These observations raise the possibility that TF
and TGF-beta may contribute to the increased cardiovascular disease that
accompanies obesity and related non-insulin-dependent diabetes mellitus, and that
the adipocyte plays a key role in this process. The recent demonstration that TF
also influences angiogenesis, cell adhesion, and signaling suggests that its
exact role in adipose tissue physiology/pathology, may be complex.
PMID- 9636195
TI - Prothrombin deficiency results in embryonic and neonatal lethality in mice.
AB - The conversion of prothrombin (FII) to the serine protease, thrombin (FIIa), is a
key step in the coagulation cascade because FIIa triggers platelet activation,
converts fibrinogen to fibrin, and activates regulatory pathways that both
promote and ultimately suppress coagulation. However, several observations
suggest that FII may serve a broader physiological role than simply stemming
blood loss, including the identification of multiple G protein-coupled, thrombin
activated receptors, and the well-documented mitogenic activity of FIIa in in
vitro test systems. To explore in greater detail the physiological roles of FII
in vivo, FII-deficient (FII-/-) mice were generated. Inactivation of the FII gene
leads to partial embryonic lethality with more than one-half of the FII-/-
embryos dying between embryonic days 9.5 and 11.5. Bleeding into the yolk sac
cavity and varying degrees of tissue necrosis were observed in many FII-/-
embryos within this gestational time frame. However, at least one-quarter of the
FII-/- mice survived to term, but ultimately they, too, developed fatal
hemorrhagic events and died within a few days of birth. This study directly
demonstrates that FII is important in maintaining vascular integrity during
development as well as postnatal life.
PMID- 9636196
TI - Incomplete embryonic lethality and fatal neonatal hemorrhage caused by
prothrombin deficiency in mice.
AB - Deficiency of blood coagulation factor V or tissue factor causes the death of
mouse embryos by 10.5 days of gestation, suggesting that part of the blood
coagulation system is necessary for development. This function is proposed to
require either generation of the serine protease thrombin and cell signaling
through protease-activated receptors or an activity of tissue factor that is
distinct from blood clotting. We find that murine deficiency of prothrombin
clotting factor 2 (Cf2) was associated with the death of approximately 50% of
Cf2(-/-) embryos by embryonic day 10.5 (E10.5), and surviving embryos had
characteristic defects in yolk sac vasculature. Most of the remaining Cf2(-/-)
embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare
Cf2(-/-) neonates died of hemorrhage on the first postnatal day. These studies
suggest that a part of the blood coagulation system is adapted to perform a
developmental function. Other mouse models show that the absence of platelets or
of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in
development may be independent of its effects on blood coagulation and instead
may involve signal transduction on cells other than platelets.
PMID- 9636197
TI - Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal
localization of a carbonic anhydrase gene that is overexpressed in some renal
cell cancers.
AB - We report the cloning and characterization of a tumor-associated carbonic
anhydrase (CA) that was identified in a human renal cell carcinoma (RCC) by
serological expression screening with autologous antibodies. The cDNA sequence
predicts a 354-amino acid polypeptide with a molecular mass of 39,448 Da that has
features of a type I membrane protein. The predicted sequence includes a 29-amino
acid signal sequence, a 261-amino acid CA domain, an additional short
extracellular segment, a 26-amino acid hydrophobic transmembrane domain, and a
hydrophilic C-terminal cytoplasmic tail of 29 amino acids that contains two
potential phosphorylation sites. The extracellular CA domain shows 30-42%
homology with known human CAs, contains all three Zn-binding histidine residues
found in active CAs, and contains two potential sites for asparagine
glycosylation. When expressed in COS cells, the cDNA produced a 43- to 44-kDa
protein in membranes that had around one-sixth the CA activity of membranes from
COS cells transfected with the same vector expressing bovine CA IV. We have
designated this human protein CA XII. Northern blot analysis of normal tissues
demonstrated a 4.5-kb transcript only in kidney and intestine. However, in 10% of
patients with RCC, the CA XII transcript was expressed at much higher levels in
the RCC than in surrounding normal kidney tissue. The CA XII gene was mapped by
using fluorescence in situ hybridization to 15q22. CA XII is the second
catalytically active membrane CA reported to be overexpressed in certain cancers.
Its relationship to oncogenesis and its potential as a clinically useful tumor
marker clearly merit further investigation.
PMID- 9636198
TI - Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in
human atherosclerosis and regulation in macrophages by colony stimulating factors
and oxidized low density lipoprotein.
AB - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
dependent transcription factor that has been demonstrated to regulate fat cell
development and glucose homeostasis. PPARgamma is also expressed in a subset of
macrophages and negatively regulates the expression of several proinflammatory
genes in response to natural and synthetic ligands. We here demonstrate that
PPARgamma is expressed in macrophage foam cells of human atherosclerotic lesions,
in a pattern that is highly correlated with that of oxidation-specific epitopes.
Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating
factor, which are known to be present in atherosclerotic lesions, stimulated
PPARgamma expression in primary macrophages and monocytic cell lines. PPARgamma
mRNA expression was also induced in primary macrophages and THP-1 monocytic
leukemia cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA).
Inhibition of protein kinase C blocked the induction of PPARgamma expression by
TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates
PPARgamma expression in macrophages. TPA induced the expression of PPARgamma in
RAW 264.7 macrophages by increasing transcription from the PPARgamma1 and
PPARgamma3 promoters. In concert, these observations provide insights into the
regulation of PPARgamma expression in activated macrophages and raise the
possibility that PPARgamma ligands may influence the progression of
atherosclerosis.
PMID- 9636199
TI - Estimating sequestered parasite population dynamics in cerebral malaria.
AB - Clinical investigation of malaria is hampered by the lack of a method for
estimating the number of parasites that are sequestered in the tissues, for it is
these parasites that are thought to be crucial to the pathogenesis of life
threatening complications such as cerebral malaria. We present a method of
estimating this hidden population by using clinical observations of peripheral
parasitemia combined with an age-structured mathematical model of the parasite
erythrocyte cycle. Applying the model to data from 217 Gambian children
undergoing treatment for cerebral malaria we conclude that although artemether
clears parasitemia more rapidly than quinine, the clearance of sequestered
parasites is similar for the two drugs. The estimated sequestered mass was found
to be a more direct predictor of fatal outcome than clinically observed
parasitemia. This method allows a sequential analysis of sequestered parasite
population dynamics in children suffering from cerebral malaria, and the results
offer a possible explanation for why artemether provides less advantage than
might have been expected over quinine in reducing mortality despite its rapid
effect on circulating parasites.
PMID- 9636200
TI - Cloning and characterization of human inducible nitric oxide synthase splice
variants: a domain, encoded by exons 8 and 9, is critical for dimerization.
AB - The inducible nitric oxide synthase (iNOS) contains an amino-terminal oxygenase
domain, a carboxy-terminal reductase domain, and an intervening calmodulin
binding region. For the synthesis of nitric oxide (NO), iNOS is active as a
homodimer. The human iNOS mRNA is subject to alternative splicing, including
deletion of exons 8 and 9 that encode amino acids 242-335 of the oxygenase
domain. In this study, iNOS8(-)9(-) and full-length iNOS (iNOSFL) were cloned
from bronchial epithelial cells. Expression of iNOS8(-)9(-) in 293 cell line
resulted in generation of iNOS8(-)9(-) mRNA and protein but did not lead to NO
production. In contrast to iNOSFL, iNOS8(-)9(-) did not form dimers. Similar to
iNOSFL, iNOS8(-)9(-) exhibited NADPH-diaphorase activity and contained tightly
bound calmodulin, indicating that the reductase and calmodulin-binding domains
were functional. To identify sequences in exons 8 and 9 that are critical for
dimerization, iNOSFL was used to construct 12 mutants, each with deletion of
eight residues in the region encoded by exons 8 and 9. In addition, two "control"
iNOS deletion mutants were synthesized, lacking either residues 45-52 of the
oxygenase domain or residues 1131-1138 of the reductase domain. Whereas both
control deletion mutants generated NO and formed dimers, none of the 12 other
mutants formed dimers or generated NO. The region encoded by exons 8 and 9 is
critical for iNOS dimer formation and NO production but not for reductase
activity. This region could be a potential target for therapeutic interventions
aimed at inhibiting iNOS dimerization and hence NO synthesis.
PMID- 9636201
TI - Persistent inhibition of cell respiration by nitric oxide: crucial role of S
nitrosylation of mitochondrial complex I and protective action of glutathione.
AB - Both reversible and irreversible inhibition of mitochondrial respiration have
been reported following the generation of nitric oxide (NO) by cells. Using J774
cells, we have studied the effect of long-term exposure to NO on different
enzymes of the respiratory chain. Our results show that, although NO inhibits
complex IV in a way that is always reversible, prolonged exposure to NO results
in a gradual and persistent inhibition of complex I that is concomitant with a
reduction in the intracellular concentration of reduced glutathione. This
inhibition appears to result from S-nitrosylation of critical thiols in the
enzyme complex because it can be immediately reversed by exposing the cells to
high intensity light or by replenishment of intracellular reduced glutathione.
Furthermore, decreasing the concentration of reduced glutathione accelerates the
process of persistent inhibition. Our results suggest that, although NO may
regulate cell respiration physiologically by its action on complex IV, long-term
exposure to NO leads to persistent inhibition of complex I and potentially to
cell pathology.
PMID- 9636202
TI - A unified theory of carcinogenesis based on order-disorder transitions in DNA
structure as studied in the human ovary and breast.
AB - Fourier transform-infrared/statistics models demonstrate that the malignant
transformation of morphologically normal human ovarian and breast tissues
involves the creation of a high degree of structural modification (disorder) in
DNA, before restoration of order in distant metastases. Order-disorder
transitions were revealed by methods including principal components analysis of
infrared spectra in which DNA samples were represented by points in two
dimensional space. Differences between the geometric sizes of clusters of points
and between their locations revealed the magnitude of the order-disorder
transitions. Infrared spectra provided evidence for the types of structural
changes involved. Normal ovarian DNAs formed a tight cluster comparable to that
of normal human blood leukocytes. The DNAs of ovarian primary carcinomas,
including those that had given rise to metastases, had a high degree of disorder,
whereas the DNAs of distant metastases from ovarian carcinomas were relatively
ordered. However, the spectra of the metastases were more diverse than those of
normal ovarian DNAs in regions assigned to base vibrations, implying increased
genetic changes. DNAs of normal female breasts were substantially disordered
(e.g., compared with the human blood leukocytes) as were those of the primary
carcinomas, whether or not they had metastasized. The DNAs of distant breast
cancer metastases were relatively ordered. These findings evoke a unified theory
of carcinogenesis in which the creation of disorder in the DNA structure is an
obligatory process followed by the selection of ordered, mutated DNA forms that
ultimately give rise to metastases.
PMID- 9636203
TI - Epitopes close to the apolipoprotein B low density lipoprotein receptor-binding
site are modified by advanced glycation end products.
AB - Advanced glycation end products (AGEs) are thought to contribute to the abnormal
lipoprotein profiles and increased risk of cardiovascular disease of patients
with diabetes and renal failure, in part by preventing apolipoprotein B (apoB)
mediated cellular uptake of low density lipoproteins (LDL) by LDL receptors
(LDLr). It has been proposed that AGE modification at one site in apoB, almost
1,800 residues from the putative apoB LDLr-binding domain, may be sufficient to
induce an apoB conformational change that prevents binding to the LDLr. To
further explore this hypothesis, we used 29 anti-human apoB mAbs to identify
other potential sites on apoB that may be modified by in vitro advanced glycation
of LDL. Glycation of LDL caused a time-dependent decrease in its ability to bind
to the LDLr and in the immunoreactivity of six distinct apoB epitopes, including
two that flank the apoB LDLr-binding domain. ApoB appears to be modified at
multiple sites by these criteria, as the loss of glycation-sensitive epitopes was
detected on both native glycated LDL and denatured, delipidated glycated apoB.
Moreover, residues directly within the putative apoB LDLr-binding site are not
apparently modified in glycated LDL. We propose that the inability of LDL
modified by AGEs to bind to the LDLr is caused by modification of residues
adjacent to the putative LDLr-binding site that were undetected by previous
immunochemical studies. AGE modification either eliminates the direct
participation of the residues in LDLr binding or indirectly alters the
conformation of the apoB LDLr-binding site.
PMID- 9636204
TI - Boosting with recombinant vaccinia increases immunogenicity and protective
efficacy of malaria DNA vaccine.
AB - To enhance the efficacy of DNA malaria vaccines, we evaluated the effect on
protection of immunizing with various combinations of DNA, recombinant vaccinia
virus, and a synthetic peptide. Immunization of BALB/c mice with a plasmid
expressing Plasmodium yoelii (Py) circumsporozoite protein (CSP) induces H-2Kd
restricted CD8+ cytotoxic T lymphocyte (CTL) responses and CD8+ T cell- and
interferon (IFN)-gamma-dependent protection of mice against challenge with Py
sporozoites. Immunization with a multiple antigenic peptide, including the only
reported H-2Kd-restricted CD8+ T cell epitope on the PyCSP (PyCSP CTL multiple
antigenic peptide) and immunization with recombinant vaccinia expressing the
PyCSP induced CTL but only modest to minimal protection. Mice were immunized with
PyCSP DNA, PyCSP CTL multiple antigenic peptide, or recombinant vaccinia
expressing PyCSP, were boosted 9 wk later with the same immunogen or one of the
others, and were challenged. Only mice immunized with DNA and boosted with
vaccinia PyCSP (D-V) (11/16: 69%) or DNA (D-D) (7/16: 44%) had greater protection
(P < 0. 0007) than controls. D-V mice had significantly higher individual levels
of antibodies and class I-restricted CTL activity than did D-D mice; IFN-gamma
production by ELIspot also was higher in D-V than in D-D mice. In a second
experiment, three different groups of D-V mice each had higher levels of
protection than did D-D mice, and IFN-gamma production was significantly greater
in D-V than in D-D mice. The observation that priming with PyCSP DNA and boosting
with vaccinia-PyCSP is more immunogenic and protective than immunizing with PyCSP
DNA alone supports consideration of a similar sequential immunization approach in
humans.
PMID- 9636205
TI - Late-onset minor and major depression: early evidence for common neuroanatomical
substrates detected by using MRI.
AB - The purpose of our study was to examine the neuroanatomical correlates of late
onset minor and major depression and to compare them with similar measures
obtained from nondepressed controls. Our study groups were comprised of 18
patients with late-onset minor depression, 35 patients diagnosed with late-onset
major depression, and 30 nondepressed controls. All subjects were scanned by
using a 1. 5-tesla MRI scanner. Absolute whole brain volume and normalized
measures of prefrontal and temporal lobe volumes were obtained and used for
comparison among groups. Our findings indicate that patients with minor
depression present with specific neuroanatomical abnormalities that are
comparable with the major depression group but significantly different from the
controls. Normalized prefrontal lobe volumes show a significant linear trend with
severity of depression, with volumes decreasing with illness severity. Whole
brain volumes did not differ significantly among groups. These findings have
broad implications for the biology of late-life depression and suggest that there
may be common neurobiological substrates that underlie all clinically significant
forms of late-onset mood disturbances.
PMID- 9636206
TI - Inactivation of tyrosine hydroxylase by nitration following exposure to
peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
AB - The decrement in dopamine levels exceeds the loss of dopaminergic neurons in
Parkinson's disease (PD) patients and experimental models of PD. This discrepancy
is poorly understood and may represent an important event in the pathogenesis of
PD. Herein, we report that the rate-limiting enzyme in dopamine synthesis,
tyrosine hydroxylase (TH), is a selective target for nitration following exposure
of PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+).
Nitration of TH also occurs in mouse striatum after MPTP administration.
Nitration of tyrosine residues in TH results in loss of enzymatic activity. In
the mouse striatum, tyrosine nitration-mediated loss in TH activity parallels the
decline in dopamine levels whereas the levels of TH protein remain unchanged for
the first 6 hr post MPTP injection. Striatal TH was not nitrated in mice
overexpressing copper/zinc superoxide dismutase after MPTP administration,
supporting a critical role for superoxide in TH tyrosine nitration. These results
indicate that tyrosine nitration-induced TH inactivation and consequently
dopamine synthesis failure, represents an early and thus far unidentified
biochemical event in MPTP neurotoxic process. The resemblance of the MPTP model
with PD suggests that a similar phenomenon may occur in PD, influencing the
severity of parkisonian symptoms.
PMID- 9636207
TI - KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated
dependent fashion.
AB - The KARP-1 (Ku86 Autoantigen Related Protein-1) gene, which is expressed from the
human Ku86 autoantigen locus, appears to play a role in mammalian DNA double
strand break repair as a regulator of the DNA-dependent protein kinase complex.
Here we demonstrate that KARP-1 gene expression is significantly up-regulated
following exposure of cells to DNA damage. KARP-1 mRNA induction was completely
dependent on the ataxia telangiectasia and p53 gene products, consistent with the
presence of a p53 binding site within the second intron of the KARP-1 locus.
These observations link ataxia telangiectasia, p53, and KARP-1 in a common
pathway.
PMID- 9636208
TI - Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and
virulence of Candida albicans.
AB - There is an immediate need for identification of new antifungal targets in
opportunistic pathogenic fungi like Candida albicans. In the past, efforts have
focused on synthesis of chitin and glucan, which confer mechanical strength and
rigidity upon the cell wall. This paper describes the molecular analysis of
CaMNT1, a gene involved in synthesis of mannoproteins, the third major class of
macromolecule found in the cell wall. CaMNT1 encodes an alpha-1, 2-mannosyl
transferase, which adds the second mannose residue in a tri-mannose
oligosaccharide structure which represents O-linked mannan in C. albicans. The
deduced amino acid sequence suggests that CaMnt1p is a type II membrane protein
residing in a medial Golgi compartment. The absence of CaMnt1p reduced the
ability of C. albicans cells to adhere to each other, to human buccal epithelial
cells, and to rat vaginal epithelial cells. Both heterozygous and homozygous
Camnt1 null mutants of C. albicans showed strong attenuation of virulence in
guinea pig and mouse models of systemic candidosis, which, in guinea pigs, could
be attributed to a decreased ability to reach and/or adhere internal organs.
Therefore, correct CaMnt1p-mediated O-linked mannosylation of proteins is
critical for adhesion and virulence of C. albicans.
PMID- 9636209
TI - The crucial role of polymorphonuclear leukocytes in resistance to Salmonella
dublin infections in genetically susceptible and resistant mice.
AB - Macrophages are considered to be the mediators of resistance to extra-intestinal
Salmonella infections. Nevertheless, the initial cellular response to Salmonella
infections consists primarily of polymorphonuclear leukocytes (PMN). To determine
whether PMN serve an important function for the infected host, we made mice
neutropenic with the rat mAb to RB6-8C5 and infected them i.v. with approximately
10(3) Salmonella dublin or an isogenic derivative that lacks the virulence
plasmid (LD842). We infected BALB/c mice, which have a point mutation in the
macrophage-expressed gene Nramp1 that makes them susceptible to Salmonella, and
BALB/c.D2 congenic mice, which have the wild-type Nramp1 gene that makes them
resistant to Salmonella. Both mouse strains were resistant to LD842, and
neutropenia made only the BALB/c strain susceptible to this infection.
Neutropenic congenic mice, however, were susceptible only to wild-type S. dublin
(plasmid+). These results show a complex interplay between plasmid-virulence
genes in Salmonella, host macrophages, and PMN. Mice with normal macrophages need
PMN to defend against nontyphoid Salmonella that carry a virulence plasmid but
not against Salmonella without virulence plasmids. Mice with a mutant Nramp1 gene
need PMN to defend against all Salmonella, even those that lack virulence
plasmids. These results, plus the evidence that PMN kill Salmonella efficiently
in vitro, suggest that Salmonella have adapted to grow inside macrophages where
they are relatively sheltered from PMN. The adaptations that allow Salmonella to
survive in macrophages do not protect them from PMN.
PMID- 9636210
TI - The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope
V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop.
AB - Although infection by primary HIV type 1 (HIV-1) isolates normally requires the
functional interaction of the viral envelope protein with both CD4 and the CCR-5
coreceptor, a subset of such isolates also are able to use the distinct CCR-3
receptor. By analyzing the ability of a series of wild-type and chimeric HIV-1
envelope proteins to mediate CCR-3-dependent infection, we have determined that
CCR-3 tropism maps to the V1 and V2 variable region of envelope. Although
substitution of the V1/V2 region of a CCR-3 tropic envelope into the context of a
CCR-5 tropic envelope is both necessary and sufficient to confer CCR-3 tropism,
this same substitution has no phenotypic effect when inserted into a CXCR-4
tropic HIV-1 envelope context. However, this latter chimera acquires both CCR-3
and CCR-5 tropism when a CCR-5 tropic V3 loop sequence also is introduced. These
data demonstrate that the V1/2 region of envelope can, like the V3 loop region,
encode a particular coreceptor requirement and suggest that a functional
envelope:CCR-3 interaction may depend on the cooperative interaction of CCR-3
with both the V1/V2 and the V3 region of envelope.
PMID- 9636211
TI - A negative regulator mediates quorum-sensing control of exopolysaccharide
production in Pantoea stewartii subsp. stewartii.
AB - Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux
system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to
stimulate cognate transcriptional activators for the cell density-dependent
expression of specific target gene systems. For Pantoea stewartii subsp.
stewartii, a bacterial pathogen of sweet corn and maize, the extracellular
polysaccharide (EPS) stewartan is a major virulence factor, and its production is
controlled by quorum sensing in a population density-dependent manner. Two genes,
esaI and esaR, encode essential regulatory proteins for quorum sensing. EsaI is
the AHL signal synthase, and EsaR is the cognate gene regulator. esaI, DeltaesaR,
and DeltaesaI-esaR mutations were constructed to establish the regulatory role of
EsaR. We report here that strains containing an esaR mutation produce high levels
of EPS independently of cell density and in the absence of the AHL signal. Our
data indicate that quorum-sensing regulation in P. s. subsp. stewartii, in
contrast to most other described systems, uses EsaR to repress EPS synthesis at
low cell density, and that derepression requires micromolar amounts of AHL. In
addition, derepressed esaR strains, which synthesize EPS constitutively at low
cell densities, were significantly less virulent than the wild-type parent. This
finding suggests that quorum sensing in P. s. subsp. stewartii may be a mechanism
to delay the expression of EPS during the early stages of infection so that it
does not interfere with other mechanisms of pathogenesis.
PMID- 9636213
TI - Cocaine reward models: conditioned place preference can be established in
dopamine- and in serotonin-transporter knockout mice.
AB - Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters
for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated
sodium channels, a property not shared by methylphenidate. Several lines of
evidence have suggested that cocaine blockade of the dopamine transporter (DAT),
perhaps with additional contributions from serotonin transporter (5-HTT)
recognition, was key to its rewarding actions. We now report that knockout mice
without DAT and mice without 5-HTT establish cocaine-conditioned place
preferences. Each strain displays cocaine-conditioned place preference in this
major mouse model for assessing drug reward, while methylphenidate-conditioned
place preference is also maintained in DAT knockout mice. These results have
substantial implications for understanding cocaine actions and for strategies to
produce anticocaine medications.
PMID- 9636212
TI - Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing
Kv1.1 mRNA.
AB - The tissue distributions and physiological properties of a variety of cloned
voltage-gated potassium channel genes have been characterized extensively, yet
relatively little is known about the mechanisms controlling expression of these
genes. Here, we report studies on the regulation of Kv1.1 expressed endogenously
in the C6 glioma cell line. We demonstrate that elevation of intracellular cAMP
leads to the accelerated degradation of Kv1.1 RNA. The cAMP-induced decrease in
Kv1.1 RNA is followed by a decrease in Kv1. 1 protein and a decrease in the whole
cell sustained K+ current amplitude. Dendrotoxin-I, a relatively specific blocker
of Kv1.1, blocks 96% of the sustained K+ current in glioma cells, causing a shift
in the resting membrane potential from -40 mV to -7 mV. These data suggest that
expression of Kv1.1 contributes to setting the resting membrane potential in
undifferentiated glioma cells. We therefore suggest that receptor-mediated
elevation of cAMP reduces outward K+ current density by acting at the
translational level to destabilize Kv1.1 RNA, an additional mechanism for
regulating potassium channel gene expression.
PMID- 9636215
TI - Low dimensionality of supraspinally induced force fields.
AB - Recent experiments using electrical and N-methyl-D-aspartate microstimulation of
the spinal cord gray matter and cutaneous stimulation of the hindlimb of
spinalized frogs have provided evidence for a modular organization of the frog's
spinal cord circuitry. A "module" is a functional unit in the spinal cord
circuitry that generates a specific motor output by imposing a specific pattern
of muscle activation. The output of a module can be characterized as a force
field: the collection of the isometric forces generated at the ankle over
different locations in the leg's workspace. Different modules can be combined
independently so that their force fields linearly sum. The goal of this study was
to ascertain whether the force fields generated by the activation of supraspinal
structures could result from combinations of a small number of modules. We
recorded a set of force fields generated by the electrical stimulation of the
vestibular nerve in seven frogs, and we performed a principal component analysis
to study the dimensionality of this set. We found that 94% of the total variation
of the data is explained by the first five principal components, a result that
indicates that the dimensionality of the set of fields evoked by vestibular
stimulation is low. This result is compatible with the hypothesis that vestibular
fields are generated by combinations of a small number of spinal modules.
PMID- 9636214
TI - Dynamic characteristics and adaptability of mouse vestibulo-ocular and
optokinetic response eye movements and the role of the flocculo-olivary system
revealed by chemical lesions.
AB - The dynamic characteristics of reflex eye movements were measured in two strains
of chronically prepared mice by using an infrared television camera system. The
horizontal vestibulo-ocular reflex (HVOR) and horizontal optokinetic response
(HOKR) were induced by sinusoidal oscillations of a turntable, in darkness, by 10
degrees (peak to peak) at 0.11-0.50 Hz and of a checked-pattern screen, in light,
by 5-20 degreesat 0.11-0.17 Hz, respectively. The gains and phases of the HVOR
and HOKR of the C57BL/6 mice were nearly equivalent to those of rabbits and rats,
whereas the 129/Sv mice exhibited very low gains in the HVOR and moderate phase
lags in the HOKR, suggesting an inherent sensory-motor anomaly. Adaptability of
the HOKR was examined in C57BL/6 mice by sustained screen oscillation. When the
screen was oscillated by 10 degrees at 0.17 Hz, which induced sufficient retinal
slips, the gain of the HOKR increased by 0.08 in 1 h on average, whereas the
stimuli that induced relatively small or no retinal slips affected the gain very
little. Lesions of the flocculi induced by local applications of 0. 1% ibotenic
acid and lesions of the inferior olivary nuclei induced by i.p. injection of 3
acetylpyridine in C57BL/6 mice little affected the dynamic characteristics of the
HVOR and HOKR, but abolished the adaptation of the HOKR. These results indicate
that the olivo-floccular system plays an essential role in the adaptive control
of the ocular reflex in mice, as suggested in other animal species. The data
presented provide the basis for analyzing the reflex eye movements of genetically
engineered mice.
PMID- 9636216
TI - Dynamic mapping at the laminar level of odor-elicited responses in rat olfactory
bulb by functional MRI.
AB - We have applied functional MRI (fMRI) based on blood oxygenation level-dependent
(BOLD) image-contrast to map odor-elicited olfactory responses at the laminar
level in the rat olfactory bulb (OB) elicited by iso-amyl acetate (10(-2)
dilution of saturated vapor) with spatial and temporal resolutions of
220x220x1,000 micro(m) and 36 s. The laminar structure of the OB was clearly
depicted by high-resolution in vivo anatomical MRI with spatial resolution of
110x110x1,000 micro(m). In repeated BOLD fMRI measurements, highly significant (P
< 0.001) foci were located in the outer layers of both OBs. The occurrence of
focal OB activity within a domain at the level of individual glomeruli or groups
of glomeruli was corroborated on an intra- and inter-animal basis under
anesthetized conditions with this noninvasive method. The dynamic studies
demonstrated that the odor-elicited BOLD activations were highly reproducible on
a time scale of minutes, whereas over tens of minutes the activations sometimes
varied slowly. We found large BOLD signal (DeltaS/S = 10-30%) arising from the
olfactory nerve layer, which is devoid of synapses and composed of unmyelinated
fibers and glial cells. Our results support previous studies with other methods
showing that odors elicit activity within glomerular layer domains in the
mammalian OB, and extend the analysis to shorter time periods at the level of
individual glomeruli or groups of glomeruli. With further improvement, BOLD fMRI
should be ideal for systematic analysis of the functional significance of
individual glomeruli in olfactory information encoding and of spatiotemporal
processing within the olfactory system.
PMID- 9636217
TI - Functional organization of spatial and nonspatial working memory processing
within the human lateral frontal cortex.
AB - The present study used functional magnetic resonance imaging to demonstrate that
performance of visual spatial and visual nonspatial working memory tasks involve
the same regions of the lateral prefrontal cortex when all factors unrelated to
the type of stimulus material are appropriately controlled. These results provide
evidence that spatial and nonspatial working memory may not be mediated,
respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal
lobe, as widely assumed, and support the alternative notion that specific regions
of the lateral prefrontal cortex make identical executive functional
contributions to both spatial and nonspatial working memory.
PMID- 9636218
TI - Nerve growth factor inhibits sympathetic neurons' response to an injury cytokine.
AB - Axonal damage to adult peripheral neurons causes changes in neuronal gene
expression. For example, axotomized sympathetic, sensory, and motor neurons begin
to express galanin mRNA and protein, and recent evidence suggests that galanin
plays a role in peripheral nerve regeneration. Previous studies in sympathetic
and sensory neurons have established that galanin expression is triggered by two
consequences of nerve transection: the induction of leukemia inhibitory factor
(LIF) and the reduction in the availability of the target-derived factor, nerve
growth factor. It is shown in the present study that no stimulation of galanin
expression occurs following direct application of LIF to intact neurons in the
superior cervical sympathetic ganglion. Injection of animals with an antiserum to
nerve growth factor concomitant with the application of LIF, on the other hand,
does stimulate galanin expression. The data suggest that the response of neurons
to an injury factor, LIF, is affected by whether the neurons still receive
trophic signals from their targets.
PMID- 9636219
TI - Prominence of the dopamine D2 short isoform in dopaminergic pathways.
AB - As a result of alternative splicing, the D2 gene of the dopamine receptor family
exists in two isoforms. The D2 long is characterized by the insertion of 29 amino
acids in the third cytoplasmic loop, which is absent in the short isoform. We
have produced subtype-specific antibodies against both the D2 short and D2 long
isoforms and found a unique compartmentalization between these two isoforms in
the primate brain. The D2 short predominates in the cell bodies and projection
axons of the dopaminergic cell groups of the mesencephalon and hypothalamus,
whereas the D2 long is more strongly expressed by neurons in the striatum and
nucleus accumbens, structures targeted by dopaminergic fibers. These results show
that the splice variants of the dopamine D2 receptor are differentially
distributed and possess distinct functions. The strategic localization of the D2
short isoform in dopaminergic cell bodies and axons strongly suggests that this
isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is
primarily a postsynaptic receptor.
PMID- 9636220
TI - Mutation in the tau gene in familial multiple system tauopathy with presenile
dementia.
AB - Familial multiple system tauopathy with presenile dementia (MSTD) is a
neurodegenerative disease with an abundant filamentous tau protein pathology. It
belongs to the group of familial frontotemporal dementias with Parkinsonism
linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders
whose genetic basis is unknown. We now report a G to A transition in the intron
following exon 10 of the gene for microtubule-associated protein tau in familial
MSTD. The mutation is located at the 3' neighboring nucleotide of the GT splice
donor site and disrupts a predicted stem-loop structure. We also report an
abnormal preponderance of soluble tau protein isoforms with four microtubule
binding repeats over isoforms with three repeats in familial MSTD. This most
likely accounts for our previous finding that sarkosyl-insoluble tau protein
extracted from the filamentous deposits in familial MSTD consists only of tau
isoforms with four repeats. These findings reveal that a departure from the
normal ratio of four-repeat to three-repeat tau isoforms leads to the formation
of abnormal tau filaments. The results show that dysregulation of tau protein
production can cause neurodegeneration and imply that the FTDP-17 gene is the tau
gene. This work has major implications for Alzheimer's disease and other
tauopathies.
PMID- 9636221
TI - Dopamine-dependent responses to morphine depend on glucocorticoid receptors.
AB - Previous work has shown that glucocorticoid hormones facilitate the behavioral
and dopaminergic effects of morphine. In this study we examined the possible role
in these effects of the two central corticosteroid receptor types:
mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish
this, specific antagonists of these receptors were infused
intracerebroventricularly and 2 hr later we measured: (i) locomotor activity
induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity
induced by an infusion of morphine (1 microg per side) into the ventral tegmental
area, which is a dopamine-dependent behavioral response to morphine; (iii)
morphine-induced dopamine release in the nucleus accumbens, a dopaminergic
projection site mediating the locomotor and reinforcing effects of drugs of
abuse. Blockade of MRs by spironolactone had no significant effects on locomotion
induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or
RU39305, which is devoid of antiprogesterone effects, reduced the locomotor
response to morphine, and this effect was dose dependent. GR antagonists also
reduced the locomotor response to intraventral tegmental area morphine as well as
the basal and morphine-induced increase in accumbens dopamine, as measured by
microdialysis in freely moving rats. In contrast, spironolactone did not modify
dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the
dopamine-dependent behavioral effects of morphine, probably by facilitating
dopamine release. The possibility of decreasing the behavioral and dopaminergic
effects of opioids by an acute administration of GR antagonists may open new
therapeutic strategies for treatment of drug addiction.
PMID- 9636222
TI - Phosphatidylcholine-specific phospholipase C regulates glutamate-induced nerve
cell death.
AB - Phosphatidylcholine-specific phospholipase C (PC-PLC) is a necessary intermediate
in transducing apoptotic signals for tumor necrosis factor and Fas/Apo-1 ligands
in nonneuronal cells. The data presented here show that PC-PLC also is required
in oxidative glutamate-induced programmed cell death of both immature cortical
neurons and a hippocampal nerve cell line, HT22. In oxidative glutamate toxicity,
which is distinct from excitotoxicity, glutamate interferes with cystine uptake
by blocking the cystine/glutamate antiporter, indirectly causing a depletion of
intracellular glutathione. A PC-PLC inhibitor blocks oxidative glutamate
toxicity, and exogenous PC-PLC potentiates glutamate toxicity. The inhibition of
PC-PLC uncouples the cystine uptake from glutamate inhibition, allowing the
maintenance of glutathione synthesis and cell viability. These data suggest that
PC-PLC modulates neuronal cell death through a mechanism that is distinct from
that involved in nonneuronal apoptosis.
PMID- 9636223
TI - Activation of ventrolateral preoptic neurons by the somnogen prostaglandin D2.
AB - Prostaglandin D2 (PGD2) is an extensively studied sleep-promoting substance, but
the neuroanatomical basis of PGD2-induced sleep is only partially understood. To
determine potential regions involved in this response, we used Fos
immunohistochemistry to identify neurons activated by infusion of PGD2 into the
subarachnoid space below the rostral basal forebrain. PGD2 increased nonrapid eye
movement sleep and induced striking expression of Fos in the ventrolateral
preoptic area (VLPO), a cluster of neurons that may promote sleep by inhibiting
the tuberomammillary nucleus, the source of the ascending histaminergic arousal
system. Fos expression in the VLPO was positively correlated with the preceding
amount of sleep and negatively correlated with Fos expression in the
tuberomammillary nucleus. PGD2 also increased Fos immunoreactivity in the basal
leptomeninges and several regions implicated in autonomic regulation. These
observations suggest that PGD2 may induce sleep via leptomeningeal PGD2 receptors
with subsequent activation of the VLPO.
PMID- 9636224
TI - Antisense oligonucleotides against alpha1E reduce R-type calcium currents in
cerebellar granule cells.
AB - Many neurons of the central nervous system display multiple high voltage
activated Ca2+ currents, pharmacologically classified as L-, N-, P-, Q-, and R
type. Of these current types, the R-type is the least understood. The leading
candidate for the molecular correlate of R-type currents in cerebellar granule
cells is the alpha1E subunit, which yields Ca2+ currents very similar to the R
type when expressed in heterologous systems. As a complementary approach, we
tested whether antisense oligonucleotides against alpha1E could decrease the
expression of R-type current in rat cerebellar granule neurons in culture. Cells
were supplemented with either antisense or sense oligonucleotides and whole-cell
patch clamp recordings were obtained after 6-8 days in vitro. Incubation with
alpha1E antisense oligonucleotide caused a 52.5% decrease in the peak R-type
current density, from -10 +/- 0.6 picoamperes/picofarad (pA/pF) (n = 6) in the
untreated controls to -4.8 +/- 0.8 pA/pF (n = 11) (P < 0.01). In contrast, no
significant changes in the current expression were seen in sense oligonucleotide
treated cells (-11.3 +/- 3.2 pA/pF). The specificity of the alpha1E antisense
oligonucleotides was supported by the lack of change in estimates of the P/Q
current amplitude. Furthermore, antisense and sense oligonucleotides against
alpha1A did not affect R-type current expression (-11.5 +/- 1.7 and -11.7 +/- 1.7
pA/pF, respectively), whereas the alpha1A antisense oligonucleotide significantly
reduced whole cell currents under conditions in which P/Q current is dominant.
Our results support the hypothesis that members of the E class of alpha1 subunits
support the high voltage-activated R-type current in cerebellar granule cells.
PMID- 9636225
TI - Proteinase-activated receptor 2 (PAR2)-activating peptides: identification of a
receptor distinct from PAR2 that regulates intestinal transport.
AB - The effects of PAR2-activating PAR2-activating peptides, SLIGRL (SL)-NH2, and
trans-cinnamoyl-LIGRLO (tc)-NH2 were compared with the action of trypsin,
thrombin, and the PAR1 selective-activating peptide: Ala-parafluoroPhe-Arg
cyclohexylAla-Citrulline-Tyr (Cit)-NH2 for stimulating intestinal ion transport.
These agonists were added to the serosa of stripped rat jejunum segments mounted
in Ussing chambers, and short circuit current (Isc) was used to monitor active
ion transport. The relative potencies of these agonists also were evaluated in
two bioassays specific for the activation of rat PAR2: a cloned rat PAR2 cell
calcium-signaling assay (PAR2-KNRK cells) and an aorta ring relaxation (AR)
assay. In the Isc assay, all agonists, except thrombin, induced an Isc increase.
The SL-NH2-induced Isc changes were blocked by indomethacin but not by
tetrodotoxin. The relative potencies of the agonists in the Isc assay
(trypsin>>SL-NH2>tc-NH2>Cit-NH2) were strikingly different from their relative
potencies in the cloned PAR2-KNRK cell calcium assay (trypsin>>>tc-NH2 congruent
with SL-NH2>>>Cit-NH2) and in the AR assay (trypsin>>>tc-NH2 congruent with SL
NH2). Furthermore, all agonists were maximally active in the PAR2-KNRK cell and
AR assays at concentrations that were one (PAR2 -activating peptides) or two
(trypsin) orders of magnitude lower than those required to activate intestinal
transport. Based on the distinct potency profile for these agonists and the
considerable differences in the concentration ranges required to induce an Isc
effect in the intestinal assay compared with the PAR2-KNRK and AR assays, we
conclude that a proteinase-activated receptor, pharmacologically distinct from
PAR2 and PAR1, is present in rat jejunum and regulates intestinal transport via a
prostanoid-mediated mechanism.
PMID- 9636226
TI - Evidence of insulin-stimulated phosphorylation and activation of the mammalian
target of rapamycin mediated by a protein kinase B signaling pathway.
AB - The effects of insulin on the mammalian target of rapamycin, mTOR, were
investigated in 3T3-L1 adipocytes. mTOR protein kinase activity was measured in
immune complex assays with recombinant PHAS-I as substrate. Insulin-stimulated
kinase activity was clearly observed when immunoprecipitations were conducted
with the mTOR antibody, mTAb2. Insulin also increased by severalfold the 32P
content of mTOR that was determined after purifying the protein from 32P-labeled
adipocytes with rapamycin.FKBP12 agarose beads. Insulin affected neither the
amount of mTOR immunoprecipitated nor the amount of mTOR detected by
immunoblotting with mTAb2. However, the hormone markedly decreased the reactivity
of mTOR with mTAb1, an antibody that activates the mTOR protein kinase. The
effects of insulin on increasing mTOR protein kinase activity and on decreasing
mTAb1 reactivity were abolished by incubating mTOR with protein phosphatase 1.
Interestingly, the epitope for mTAb1 is located near the COOH terminus of mTOR in
a 20-amino acid region that includes consensus sites for phosphorylation by
protein kinase B (PKB). Experiments were performed in MER-Akt cells to
investigate the role of PKB in controlling mTOR. These cells express a PKB-mutant
estrogen receptor fusion protein that is activated when the cells are exposed to
4-hydroxytamoxifen. Activating PKB with 4-hydroxytamoxifen mimicked insulin by
decreasing mTOR reactivity with mTAb1 and by increasing the PHAS-I kinase
activity of mTOR. Our findings support the conclusion that insulin activates mTOR
by promoting phosphorylation of the protein via a signaling pathway that contains
PKB.
PMID- 9636227
TI - A neuromodulatory role of interleukin-1beta in the hippocampus.
AB - It is widely accepted that interleukin-1beta (IL-1beta), a cytokine produced not
only by immune cells but also by glial cells and certain neurons influences brain
functions during infectious and inflammatory processes. It is still unclear,
however, whether IL-1 production is triggered under nonpathological conditions
during activation of a discrete neuronal population and whether this production
has functional implications. Here, we show in vivo and in vitro that IL-1beta
gene expression is substantially increased during long-term potentiation of
synaptic transmission, a process considered to underlie certain forms of learning
and memory. The increase in gene expression was long lasting, specific to
potentiation, and could be prevented by blockade of potentiation with the N
methyl-D-aspartate (NMDA) receptor antagonist, (+/-)-2-amino-5-phosphonopentanoic
acid (AP-5). Furthermore, blockade of IL-1 receptors by the specific interleukin
1 receptor antagonist (IL-1ra) resulted in a reversible impairment of long-term
potentiation maintenance without affecting its induction. These results show for
the first time that the production of biologically significant amounts of IL
1beta in the brain can be induced by a sustained increase in the activity of a
discrete population of neurons and suggest a physiological involvement of this
cytokine in synaptic plasticity.
PMID- 9636228
TI - Pancreatic beta cells synthesize and secrete nerve growth factor.
AB - Differentiation and function of pancreatic beta cells are regulated by a variety
of hormones and growth factors, including nerve growth factor (NGF). Whether this
is an endocrine or autocrine/paracrine role for NGF is not known. We demonstrate
that NGF is produced and secreted by adult rat pancreatic beta cells. NGF
secretion is increased in response to elevated glucose or potassium, but
decreased in response to dibutyryl cAMP. Moreover, steady-state levels of NGF
mRNA are down-regulated by dibutyryl cAMP, which is opposite to the effect of
cAMP on insulin release. NGF-stimulated changes in morphology and function are
mediated by high-affinity Trk A receptors in other mammalian cells. Trk A
receptors are present in beta cells and steady-state levels of Trk A mRNA are
modulated by NGF and dibutyryl cAMP. Taken together, these findings suggest
endocrine and autocrine roles for pancreatic beta-cell NGF, which, in turn, could
be related to the pathogenesis of diabetes mellitus where serum NGF levels are
diminished.
PMID- 9636229
TI - Conformational changes couple Na+ and glucose transport.
AB - The mechanism by which cotransport proteins couple their substrates across cell
membranes is not known. A commonly proposed model is that cotransport results
from ligand-induced conformational transitions that change the accessibility of
ligand-binding sites from one side of the membrane to the other. To test this
model, we have measured the accessibility of covalent probes to a cysteine
residue (Q457C) placed in the putative sugar-translocation domain of the
Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport
sugar, but transport was abolished after alkylation by methanethiosulfonate
reagents. Alkylation blocked sugar translocation but not sugar binding.
Accessibility of Q457C to alkylating reagents required external Na+ and was
blocked by external sugar and phlorizin. The voltage dependence of accessibility
was directly correlated with the presteady-state charge movement of SGLT1.
Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the
time course and level of changes in fluorescence closely followed the presteady
state charge movement. We conclude that conformational changes are responsible
for the coupling of Na+ and sugar transport and that Q457 plays a critical role
in sugar translocation by SGLT1.
PMID- 9636230
TI - Adenosine acts by A1 receptors to stimulate release of prolactin from anterior
pituitaries in vitro.
AB - Adenosine has been identified in the anterior pituitary gland and is secreted
from cultured folliculostellate (FS) cells. To determine whether adenosine
controls the secretion of anterior pituitary hormones in vitro, adenosine was
incubated with anterior pituitaries. It stimulated prolactin (PRL) release at the
lowest concentration used (10(-10) M); the stimulation peaked at 10(-8) M with a
threefold increase in release and declined to minimal stimulation at 10(-4) and
10(-3) M. Follicle-stimulating hormone release was maximally inhibited at 10(-8)
M, whereas luteinizing hormone release was not significantly inhibited. Two
selective A1 adenosine receptor antagonists (10(-7) or 10(-5) M) had no effect on
basal PRL release, but either antagonist completely blocked the response to the
most effective concentration of adenosine (10(-8) M). In contrast, a highly
specific A2 receptor antagonist (10(-7) or 10(-5) M) had no effect on basal PRL
release or the stimulation of PRL release induced by adenosine (10(-8) M). We
conclude that adenosine acts to stimulate PRL release in vitro by activating A1
receptors. Since the A1 receptors decrease intracellular-free calcium, this would
decrease the activation of nitric oxide synthase in the FS cells, resulting in
decreased release of nitric oxide (NO). NO inhibits PRL release by activating
guanylate cyclase that synthesizes cGMP from GTP; cGMP concentrations increase in
the lactotrophs leading to inhibition of PRL release. In the case of adenosine,
NO release from the FS cells decreases, resulting in decreased concentrations of
NO in the lactotrophs, consequent decreased cGMP formation, and resultant
increased PRL release.
PMID- 9636231
TI - Eskimo1 mutants of Arabidopsis are constitutively freezing-tolerant.
AB - Temperate plants develop a greater ability to withstand freezing in response to a
period of low but nonfreezing temperatures through a complex, adaptive process of
cold acclimation. Very little is known about the signaling processes by which
plants perceive the low temperature stimulus and transduce it into the nucleus to
activate genes needed for increased freezing tolerance. To help understand the
signaling processes, we have isolated mutants of Arabidopsis that are
constitutively freezing-tolerant in the absence of cold acclimation. Freezing
tolerance of wild-type Arabidopsis was increased from -5.5 degreesC to -12.6
degreesC by cold acclimation whereas the freezing tolerance of 26 mutant lines
ranged from -6.8 degreesC to -10.6 degreesC in the absence of acclimation. Plants
with mutations at the eskimo1 (esk1) locus accumulated high levels of proline, a
compatible osmolyte, but did not exhibit constitutively increased expression of
several cold-regulated genes involved in freezing tolerance. RNA gel blot
analysis suggested that proline accumulation in esk1 plants was mediated by
regulation of transcript levels of genes involved in proline synthesis and
degradation. The characterization of esk1 mutants and results from other mutants
suggest that distinct signaling pathways activate different aspects of cold
acclimation and that activation of one pathway can result in considerable
freezing tolerance without activation of other pathways.
PMID- 9636232
TI - The specific features of methionine biosynthesis and metabolism in plants.
AB - Plants, unlike other higher eukaryotes, possess all the necessary enzymatic
equipment for de novo synthesis of methionine, an amino acid that supports
additional roles than simply serving as a building block for protein synthesis.
This is because methionine is the immediate precursor of S-adenosylmethionine
(AdoMet), which plays numerous roles of being the major methyl-group donor in
transmethylation reactions and an intermediate in the biosynthesis of polyamines
and of the phytohormone ethylene. In addition, AdoMet has regulatory function in
plants behaving as an allosteric activator of threonine synthase. Among the
AdoMet-dependent reactions occurring in plants, methylation of cytosine residues
in DNA has raised recent interest because impediment of this function alters
plant morphology and induces homeotic alterations in flower organs. Also, AdoMet
metabolism seems somehow implicated in plant growth via an as yet fully
understood link with plant-growth hormones such as cytokinins and auxin and in
plant pathogen interactions. Because of this central role in cellular metabolism,
a precise knowledge of the biosynthetic pathways that are responsible for
homeostatic regulation of methionine and AdoMet in plants has practical
implications, particularly in herbicide design.
PMID- 9636233
TI - Mitochondrial localization of a NADP-dependent [corrected] isocitrate
dehydrogenase isoenzyme by using the green fluorescent protein as a marker.
AB - In this work, we describe the isolation of a new cDNA encoding an NADP-dependent
isocitrate dehydrogenase (ICDH). The nucleotide sequence in its 5' region gives a
deduced amino acid sequence indicative of a targeting peptide. However, even if
this cDNA clearly encodes a noncytosolic ICDH, it is not possible to say from the
targeting peptide sequence to which subcellular compartment the protein is
addressed. To respond to this question, we have transformed tobacco plants with a
construct containing the entire targeting signal-encoding sequence in front of a
modified green fluorescent protein (GFP) gene. This construct was placed under
the control of the cauliflower mosaic virus 35S promoter, and transgenic tobacco
plants were regenerated. At the same time, and as a control, we also have
transformed tobacco plants with the same construct but lacking the nucleotide
sequence corresponding to the ICDH-targeting peptide, in which the GFP is
retained in the cytoplasm. By optical and confocal microscopy of leaf epiderm and
Western blot analyses, we show that the putative-targeting sequence encoded by
the cDNA addresses the GFP exclusively into the mitochondria of plant cells.
Therefore, we conclude that this cDNA encodes a mitochondrial ICDH.
PMID- 9636234
TI - Gene-for-gene disease resistance without the hypersensitive response in
Arabidopsis dnd1 mutant.
AB - The cell death response known as the hypersensitive response (HR) is a central
feature of gene-for-gene plant disease resistance. A mutant line of Arabidopsis
thaliana was identified in which effective gene-for-gene resistance occurs
despite the virtual absence of HR cell death. Plants mutated at the DND1 locus
are defective in HR cell death but retain characteristic responses to avirulent
Pseudomonas syringae such as induction of pathogenesis-related gene expression
and strong restriction of pathogen growth. Mutant dnd1 plants also exhibit
enhanced resistance against a broad spectrum of virulent fungal, bacterial, and
viral pathogens. The resistance against virulent pathogens in dnd1 plants is
quantitatively less strong and is differentiable from the gene-for-gene
resistance mediated by resistance genes RPS2 and RPM1. Levels of salicylic acid
compounds and mRNAs for pathogenesis-related genes are elevated constitutively in
dnd1 plants. This constitutive induction of systemic acquired resistance may
substitute for HR cell death in potentiating the stronger gene-for-gene defense
response. Although cell death may contribute to defense signal transduction in
wild-type plants, the dnd1 mutant demonstrates that strong restriction of
pathogen growth can occur in the absence of extensive HR cell death in the gene
for-gene resistance response of Arabidopsis against P. syringae.
PMID- 9636235
TI - Histidine kinase activity of the ETR1 ethylene receptor from Arabidopsis.
AB - ETR1 represents a prototypical ethylene receptor. Homologues of ETR1 have been
identified in Arabidopsis as well as in other plant species, indicating that
ethylene perception involves a family of receptors and that the mechanism of
ethylene perception is conserved in plants. The amino-terminal half of ETR1
contains a hydrophobic domain responsible for ethylene binding and membrane
localization. The carboxyl-terminal half of the polypeptide contains domains with
homology to histidine kinases and response regulators, signaling motifs
originally identified in bacteria. The putative histidine kinase domain of ETR1
was expressed in yeast as a fusion protein with glutathione S-transferase and
affinity purified. Autophosphorylation of the purified fusion protein was
observed on incubation with radiolabeled ATP. The incorporated phosphate was
resistant to treatment with 3 M NaOH, but was sensitive to 1 M HCl, consistent
with phosphorylation of histidine. Autophosphorylation was abolished by mutations
that eliminated either the presumptive site of phosphorylation (His-353) or
putative catalytic residues within the kinase domain. Truncations were used to
delineate the region required for histidine kinase activity. An examination of
cation requirements indicated that ETR1 requires Mn2+ for autophosphorylation.
These results demonstrate that higher plants contain proteins with histidine
kinase activity. Furthermore, these results indicate that aspects of ethylene
signaling may be regulated by changes in histidine kinase activity of the
receptor.
PMID- 9636236
TI - The interspecific mass-density relationship and plant geometry.
AB - We present an a priori theoretical framework for the interspecific allometric
relationship between stand mass and plant population density. Our model predicts
a slope of -1/3 between the logarithm of stand mass and the logarithm of stand
density, thus conflicting with a previously assumed slope of -1/2. Our model
rests on a heuristic separation of resource-limited living mass and structural
mass in the plant body. We point out that because of similar resource
requirements among plants of different sizes, a nonzero plant mass-density slope
is primarily defined by structural mass. Specifically, the slope is a result of
(i) the physical size-dependent relationship between stem width and height, (ii)
foliage-dependent demands of conductance, and (iii) the cumulative nature of
structural mass. The data support our model, both when the potential sampling
bias of taxonomic relatedness is accounted for and when it is not. Independent
contrasts analyses show that observed relationships among variables are not
significantly different from the assumptions made to build the model or from its
a priori predictions. We note that the dependence of the plant mass-density slope
on the functions of structural mass provides a cause for the difference from the
zero slope found in the animal population mass-density relationship; for the most
part, animals do not have a comparable cumulative tissue type.
PMID- 9636237
TI - Brain mechanisms of quantity are similar in 5-year-old children and adults.
AB - Both 5-year-old children and adults determine the quantity of a number by the use
of a similar parietal lobe mechanism. Event related potentials indicate that
input from Arabic digits and from dot patterns reach areas involved in
determining quantity about 200 ms after input. However, voluntary key presses
indicating the relation of the input to the quantity five take almost three times
as long in children. The ability to trace the networks of brain areas involved in
the learning of school subjects should aid in the design and testing of
educational methods.
PMID- 9636239
TI - Neurotransmitter transporters: regulators of function and functional regulation.
PMID- 9636238
TI - Local microdomain structure in the terminal extensions of betaA3- and betaB2
crystallins.
AB - PURPOSE: Although the crystal structures of the core domains of bovine betaB2
crystallin have been determined and those of other betagamma-crystallins modeled,
the positions of the N- and C-termini are not resolvable by X-ray
crystallography. Here we model the possible structural organization of the
terminal arms of mouse betaA3- and betaB2-crystallins and test this model against
the results of partial proteolysis. METHODS: The secondary structure of the
terminal extensions was predicted by 3 different methods, one a nearest-neighbor
method modified to use overlapping sequence tripeptides. Recombinant betaA3- and
betaB2-crystallins were expressed using baculovirus vectors in S. frugiperda Sf9
cells. Crystallins were sequenced by the Edman degradation method. RESULTS: The N
terminal extension of betaB2-crystallin includes a series of hydrophilic residues
from Q-11 to Q-9 which have high propensity of a helical conformation. The N
terminal arm of betaA3-crystallin is also predicted to have two helical segments,
from Q-24 to E-20 and M-13 to A-12. Partial characterization of the baculovirus
extract showed a thiol protease inhibited by leupeptin and E-64. As predicted by
the model, recombinant betaB2-crystallin subjected to partial proteolysis was
cleaved adjacent to the helical domain, while the N-terminal cleavage site in
recombinant betaA3-crystallin was within 1 residue of an interhelical junction.
Our model also predicts the products of partial proteolytic degradation of betaB2
and betaA3-crystallins from human, rat, bovine and chicken lenses incubated with
the protease m-calpain. CONCLUSIONS: These results suggest the existence of local
microdomain structures in the N- and C-terminal extensions of betaA3- and betaB2
crystallins, which appear to be more susceptible to proteolytic degradation in
regions adjacent to these putative domains.
PMID- 9636240
TI - Transmembrane Mg2+ currents and intracellular free Mg2+ concentration in
Paramecium tetraurelia.
AB - The properties of Mg2+ conductances in Paramecium tetraurelia were investigated
under two-electrode voltage clamp. When bathed in physiological Mg2+
concentrations (0.5 mm), depolarizing steps from rest elicited a prominent Mg2+
specific current (IMg) that has been noted previously. The dependence of this
current on extracellular Mg2+ approximated that of Mg2+-induced backward
swimming, demonstrating that IMg contributes to normal membrane excitation and
behavior in this ciliate. Closer analysis revealed that the Mg2+ current
deactivated biphasically. While this might suggest the involvement of two Mg2+
specific pathways, both tail-current components were affected similarly by
current-specific mutations and they had similar ion selectivities, suggesting a
common pathway. In contrast, a Mg2+ current activated upon hyperpolarization
could be separated into three components. The first, IMg, had similar properties
to the current activated upon depolarization. The second was a nonspecific
divalent cation current (INS) that was revealed following suppression of IMg by
eccentric mutation. The final current was relatively minor and was revealed
following suppression of IMg and INS by obstinate A gene mutation. Reversal
potential analyses suggested that IMg and INS define two intracellular
compartments that contain, respectively, low (0.4 mM) and high (8 mM)
concentrations of Mg2+. Measurement of intracellular free Mg2+ using the
fluorescent dye, Mag-fura-2, suggested that bulk [Mg2+]i rests at around 0.4 mM
in Paramecium.
PMID- 9636241
TI - Electrophysiological study of chimeric sodium channels from heart and skeletal
muscle.
AB - The alpha-subunit cDNAs encoding voltage-sensitive sodium channels of human heart
(hH1) and rat skeletal muscle (rSkM1) have been expressed in the tsA201 mammalian
cell line, in which inactivation properties appear to be normal in contrast to
Xenopus oocytes. A series of rSkM1/hH1 chimeric sodium channels has been
evaluated to identify the domains of the alpha-subunits that are responsible for
a set of electrophysiological differences between hH1 and rSkM1, namely,
midpoints and slope factors of steady-state activation and inactivation,
inactivation kinetics and recovery from inactivation kinetics and their voltage
dependence. The phenotype of chimeric channels in which each hH1 domain was
successively introduced into a rSkM1 alpha-subunit framework confirmed the
following conclusions. (i) The D4 and or/C-ter. are responsible for the slow
inactivation of hH1 sodium channels. (ii) Concerning the other differences
between rSkM1 and hH1: steady-state activation and inactivation, kinetics of
recovery from inactivation, the phenotypes are determined probably by more than
one domain of the alpha-subunit.
PMID- 9636242
TI - Flow-dependent activation of maxi K+ channels in apical membrane of rabbit
connecting tubule.
AB - The Ca2+-activated maxi K+ channel was found in the apical membrane of everted
rabbit connecting tubule (CNT) with a patch-clamp technique. The mean number of
open channels (NPo) was markedly increased from 0.007 +/- 0.004 to 0.189 +/-
0.039 (n = 7) by stretching the patch membrane in a cell-attached configuration.
This activation was suggested to be coupled with the stretch-activation of Ca2+
permeable cation channels, because the maxi K+ channel was not stretch-activated
in both the cell-attached configuration using Ca2+-free pipette and in the inside
out one in the presence of 10 mm EGTA in the cytoplasmic side. The maxi K+
channel was completely blocked by extracellular 1 microM charybdotoxin (CTX), but
was not by cytoplasmic 33 microM arachidonic acid (AA). On the other hand, the
low-conductance K+ channel, which was also found in the same membrane, was
completely inhibited by 11 microM AA, but not by 1 microM CTX. The apical K+
conductance in the CNT was estimated by the deflection of transepithelial voltage
(DeltaVt) when luminal K+ concentration was increased from 5 to 15 mEq. When the
tubule was perfused with hydraulic pressure of 0.5 KPa, the DeltaVt was only -0.
7 +/- 0.4 mV. However, an increase in luminal fluid flow by increasing perfusion
pressure to 1.5 KPa markedly enhanced DeltaVt to -9.4 +/- 0.9 mV. Luminal
application of 1 microM CTX reduced the DeltaVt to -1.3 +/- 0.6 mV significantly
in 6 tubules, whereas no significant change of DeltaVt was recorded by applying
33 microM AA into the lumen of 5 tubules (DeltaVt = -7.2 +/- 0.5 mV in control
vs. DeltaVt = -6.7 +/- 0.6 mV in AA). These results suggest that the Ca2+
activated maxi K+ channel is responsible for flow-dependent K+ secretion by
coupling with the stretch-activated Ca2+-permeable cation channel in the rabbit
CNT.
PMID- 9636243
TI - Effects of ATP-sensitive potassium channel regulators on chloride channels in the
sarcoplasmic reticulum vesicles from rabbit skeletal muscle.
AB - The lipid bilayer technique was used to examine the effects of the ATP-sensitive
K+ channel inhibitor (glibenclamide) and openers (diazoxide, minoxidil and
cromakalim) and Cl- channel activators (GABA and diazepam) on two types of
chloride channels in the sarcoplasmic reticulum (SR) from rabbit skeletal muscle.
Neither diazepam at 100 microM nor GABA at 150 microM had any significant effect
on the conductance and kinetics of the 75 pS small chloride (SCl) channel. Unlike
the 150 pS channel, the SCl channel is sensitive to cytoplasmic glibenclamide
with Ki approximately 30 microM. Glibenclamide induced reversible decline in the
values of current (maximal current amplitude, Imax and average mean current, I')
and kinetic parameters (frequency of opening Fo, probability of the channel being
open Po and mean open time, To, of the SCl channel. Glibenclamide increased mean
closed time, Tc, and was a more potent blocker from the cytoplasmic side (cis)
than from the luminal side (trans) of the channel. Diazoxide increased I', Po,
and To in the absence of ATP and Mg2+ but it had no effect on Imax and also
failed to activate or remove the glibenclamide- and ATP-induced inhibition of the
SCl channel. Minoxidil induced a transient increase in I' followed by an
inhibition of Imax, whereas cromakalim reduced Po and I' by increasing channel
transitions to the closed state and reducing To without affecting Imax. The
presence of diazoxide, minoxidil or cromakalim on the cytoplasmic side of the
channel did not prevent [ATP]cis or [glibenclamide]cis from blocking the channel.
The data suggest that the action(s) of these drugs are not due to their effects
on the phosphorylation of the channel protein. The glibenclamide- and cromakalim
induced effects on the SCl channel are mediated via a "flicker" type block
mechanism. Modulation of the SCl channel by [diazoxide]cis and [glibenclamide]cis
highlights the therapeutic potential of these drugs in regulating the Ca2+
counter current through this channel.
PMID- 9636244
TI - Tight junctions and the experimental modifications of lipid content.
AB - Tight junctions (TJs) are cell-to-cell contacts made of strands, which appear as
ridges on P faces and complementary furrows on E faces on freeze fracture
replicas. Evidences and opinions on whether these strands are composed of either
membrane-bound proteins or lipid micelles are somewhat varied. In the present
work we alter the lipid composition of Madin-Darby canine kidney monolayers using
a novel approach, while studying (i) their transepithelial electrical resistance,
a parameter that depends on the degree of sealing of the TJs; (ii) the apical-to
basolateral flux of 4 kD fluorescent dextran (JDEX), that reflects the
permeability of the intercellular spaces; (iii) the ability of TJs to restrict
apical-to-basolateral diffusion of membrane lipids; and (iv) the pattern of
distribution of endogenous and transfected occludin, the sole membrane protein
presently known to form part of the TJs. We show that changing the total
composition of phospholipids, sphingolipids, cholesterol and the content of fatty
acids, does not alter TER nor the structure of the strands. Interestingly,
enrichment with linoleic acid increases the JDEX by 631%. The fact that this
increase is not reflected in a decrease of TER, suggests that junctional strands
do not act as simple resistive elements but may contain mobile translocating
mechanisms.
PMID- 9636245
TI - Chloride conductance and Pi transport are separate functions induced by the
expression of NaPi-1 in Xenopus oocytes.
AB - Expression of the protein NaPi-1 in Xenopus oocytes has previously been shown to
induce an outwardly rectifying Cl- conductance (GCl), organic anion transport and
Na+-dependent Pi-uptake. In the present study we investigated the relation
between the NaPi-1 induced GCl and Pi-induced currents and transport. NaPi-1
expression induced Pi-transport, which was not different at 1-20 ng/oocyte NaPi-1
cRNA injection and was already maximal at 1-2 days after cRNA injection. In
contrast, GCl was augmented at increased amounts of cRNA injection (1-20
ng/oocyte) and over a five day expression period. Subsequently all experiments
were performed on oocytes injected with 20 ng/oocytes cRNA. Pi-induced currents
(Ip) could be observed in NaPi-1 expressing oocytes at high concentrations of Pi
(>/= 1 mm Pi). The amplitudes of Ip correlated well with GCl. Ip was blocked by
the Cl- channel blocker NPPB, partially Na+-dependent and completely abolished in
Cl- free solution. In contrast, Pi-transport in NaPi-1 expressing oocytes was not
NPPB sensitive, stronger depending on extracellular Na+ and weakly affected by Cl
substitution. Endogenous Pi-uptake in water-injected oocytes amounted in all
experiments to 30-50% of the Na+-dependent Pi-transport observed in NaPi-1
expressing oocytes. The properties of the endogenous Pi-uptake system (Km for Pi
> 1 mM; partial Na+- and Cl--dependence; lack of NPPB block) were similar to the
NaPi-1 induced Pi-uptake, but no Ip could be recorded at Pi-concentrations =3
mM. In summary, the present data suggest that Ip does not reflect charge transfer
related to Pi-uptake, but a Pi-mediated modulation of GCl.
PMID- 9636246
TI - Differential effects of aldosterone and vasopressin on chloride fluxes in
transimmortalized mouse cortical collecting duct cells.
AB - The effects of aldosterone and vasopressin on Cl- transport were investigated in
a mouse cortical collecting duct (mpkCCD) cell line derived from a transgenic
mouse carrying the SV40 large T antigen driven by the proximal regulatory
sequences of the L-pyruvate kinase gene. The cells had features of a tight
epithelium and expressed the amiloride-sensitive sodium channel and the cystic
fibrosis transmembrane conductance regulator (CFTR) genes. dD-arginine
vasopressin (dDAVP) caused a rapid, dose-dependent, increase in short-circuit
current (Isc). Experiments with ion channel blockers and apical ion substitution
showed that the current represented amiloride-sensitive Na+ and 5-nitro-2-(3
phenylpropylamino)benzoate-sensitive and glibenclamide-sensitive Cl- fluxes.
Aldosterone (5 x 10(-7)M for 3 or 24 hr) stimulated Isc and apical-to-basal 22Na+
flux by 3-fold. 36Cl- flux studies showed that dDAVP and aldosterone stimulated
net Cl- reabsorption and that dDAVP potentiated the action of aldosterone on Cl-
transport. Whereas aldosterone affected only the apical-to-basal 36Cl- flux,
dDAVP mainly increased the apical-to-basal Cl- flux and the basal-to-apical flux
of Cl- to a lesser extent. These results suggest that the discrete dDAVP-elicited
Cl- secretion involves the CFTR and that dDAVP and aldosterone may affect in
different ways the observed increased Cl- reabsorption in this model of mouse
cultured cortical collecting duct cells.
PMID- 9636248
TI - Introduction
PMID- 9636247
TI - A basolateral chloride conductance in rat lingual epithelium.
AB - We used Ussing chamber measurements and whole-cell recordings to characterize a
chloride conductance in rat lingual epithelium. Niflumic acid (NFA) and
flufenamic acid (FFA), nonsteroidal anti-inflammatory aromatic compounds known to
inhibit Cl- conductances in other tissues, reduced transepithelial short-circuit
current (Isc) in the intact dorsal anterior rat tongue epithelium when added from
the serosal side, and reduced whole-cell currents in rat fungiform taste cells.
In both Ussing chamber and patch-clamp experiments, the effect of NFA was
mimicked by replacement of bath Cl- with methanesulfonate or gluconate. In low Cl
bath solution, the effect of NFA on whole-cell current was reduced. Replacement
of bath Ca2+ with Ba2+ reduced the whole-cell Cl- current. We conclude that a
Ca2+-activated Cl- conductance is likely present in the basolateral membrane of
the rat lingual epithelium, and is present in the taste receptor cells from
fungiform papillae. Further experiments will be required to identify the role of
this conductance in taste transduction.
PMID- 9636250
TI - Congenital heart disease visualized
PMID- 9636249
TI - Atrioventricular septal defect.
PMID- 9636251
TI - The use of valved conduits in pediatric cardiac surgery.
AB - Extracardiac valved conduits were introduced in 1966. Currently, both aortic and
pulmonary homografts, preserved in antibiotic/nutrient solution or cryopreserved,
are used. Conduits are implanted between the right ventricle and pulmonary
artery, left ventricle and pulmonary artery, right atrium and right ventricle,
and left atrium to left ventricle. Several factors can influence longevity of
valved conduits: young age at implantation, small size of homograft, and
immunological response. In the recent study from our department, we evaluated 405
homografts implanted between 1971 and 1993 in patients who survived 90 days after
surgery. Freedom from conduit replacement at 5 and 15 years was 84% and 31% (95%
confidence limits: 80-88% and 19-43%), respectively. In multivariate analysis,
there were only two predictors of conduit longevity: (1) conduits used at
reoperation lasted less well than those used at original operation; and (2)
conduits used earlier in the series lasted longer. Conduits may have to be
replaced because of obstruction, conduit valve regurgitation,
aneurysm/pseudoaneurysm, and endocarditis. Obstructed conduits are either
replaced or outflow tract patch is used after removal of the conduit with or
without pulmonary valve implantation. Current mortality of conduit insertion is
low (5-6%). The risk of conduit replacement has also decreased in recent years to
2-3.5%
PMID- 9636252
TI - Tetralogy of Fallot with major aortopulmonary collaterals: early total repair.
AB - Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals
is a complex lesion distinguished by marked heterogeneity of pulmonary blood
supply. Over the past two decades, investigators have developed various
approaches to the management of this anomaly generally based on the concept of
staged unifocalization of pulmonary blood supply. Although such approaches may
represent an improvement on the natural history of this lesion, they remain
inadequate for a substantial portion of patients born with tetralogy of Fallot
and major aortopulmonary collaterals. Since 1992, our approach has been to
perform one-stage complete unifocalization through a midline approach in all but
a few extremely complicated patients. We aim to repair these patients early in
infancy, with an emphasis on native tissue-tissue reconstruction, in order to
optimize prospects for survival with a good functional outcome in as many
patients as possible. In this review, we present our philosophy and our
experience with unifocalization and repair in 72 patients.
PMID- 9636253
TI - Arterial switch.
AB - A relatively large spectra of anatomic variations are found within the unifying
features of discordant ventriculoarterial connections. Variants that lend
themselves to anatomic repair by the arterial switch operation are discussed,
these include transposition of the great arteries with intact ventricular septum
(TGA IVS), TGA associated with a ventricular septal defect (TGA VSD), double
outlet right ventricle with subpulmonary VSD (DORV VSD), and TGA or DORV with VSD
associated with coarctation. Double discordance with VSD, which is currently
treated by double switch or Rastelli and atrial switch and which probably
represents, in our department, the only remaining indication for atrial switch,
is not discussed. Also, we exclude TGA associated with pulmonary stenosis, which
is treated by Rastelli or REV operation.
PMID- 9636254
TI - Current status of staged reconstruction for hypoplastic left heart syndrome.
AB - Once considered a uniformly fatal condition, the outlook for newborns with
hypoplastic left heart syndrome has been dramatically altered with staged
reconstructive procedures. Refinements in operative technique and perioperative
management have been largely responsible for this improved outlook. At the
University of Michigan, 253 patients underwent the Norwood operation for classic
hypoplastic left heart syndrome between January 1990 and November 1997. Hospital
survival was 76%. Among patients considered at standard risk, survival was
significantly higher (86%) than that for those patients with important risk
factors (42%, p = 0.0001). Adverse survival was most strongly associated with
significant associated noncardiac congenital conditions (p = 0.008) and severe
preoperative obstruction to pulmonary venous return (p = 0.03). Survival
following second-stage reconstruction with a hemi-Fontan or bidirectional Glenn
procedure was 97%. The Fontan procedure has been completed in 94 of these
patients with a hospital survival rate of 88%. Survival after the Fontan
procedure improved significantly when the second stage of the reconstruction was
completed with a hemi-Fontan procedure compared to a bidirectional Glenn (98% vs
81%, p = 0.05). Among the patients considered at standard risk, actuarial
survival was 70% at 5 years. The largest decrease in survival occurred in the
first month of life and late deaths affected primarily those patients in the high
risk group. Neurodevelopmental outcome studies demonstrated normal verbal and
performance scores in the majority of patients. Staged reconstruction has
significantly improved the intermediate-term outlook for patients with
hypoplastic left heart syndrome. Factors addressing improvements in early first
stage survival would be expected to add significantly to an overall improved late
outcome.
PMID- 9636256
TI - Teaching and evaluation in pediatric cardiology
PMID- 9636255
TI - The Fontan circulation: What have we learned? What to expect?
AB - Our knowledge of the Fontan operation tends to indicate that it remains a
palliative procedure for patients with a functionally single ventricle. There is
a continuing attrition and the life expectancy of these patients is likely to be
different from the life expectancy of a population of individuals having a
biventricular circulation. This article is an essay on the rational approach for
the future management of these patients. It is suggested that a better
understanding of the continuing Fontan attrition and a more subtle way to predict
outcomes of patients who do receive the Fontan could help in establishing better
selection criteria and designing ways to prevent, delay, or treat the side
effects of this late attrition.
PMID- 9636257
TI - Neurological protection during cardiopulmonary bypass/deep hypothermia.
PMID- 9636258
TI - Recognition and prevention of neurological complications in pediatric cardiac
surgery.
AB - Because of advances in surgical and cardiopulmonary bypass techniques it is now
possible to definitively repair the vast majority of congenital heart disease in
infancy or childhood. Although the majority of survivors do not have obvious
cerebral sequelae, there is increasing disquiet about the high incidence of acute
neurological events in the immediated postoperative period as well as evidence
that at long-term follow-up there are subtle cognitive and motor deficits in
many. Some children are more at risk of neurodevelopmental problems, either
because of their cardiac (e.g. , extensive aortopulmonary collaterals) or
cerebrovascular (e.g., the propensity to large vessel dissection) anatomy or
because of genetic predisposition (e.g., to prothrombotic disorders). The
incidence may vary with the surgery (e.g., the Fontan operation) and the
cardiopulmonary bypass technique necessary to achieve an adequate technical
repair (e.g., low or no flow at deep hypothermia). Recognition of the population
at risk will lead to prevention of serious sequelae. Data collected in adults may
be misleading, and many pediatric units have developed their own practice, but
recent studies in animal models of child surgery and in children have produced
some evidence to guide management to ensure the optimal cerebral as well as
cardiac outcome. Pump flow should be maintained at least 30 ml/kg/min where
possible, with inotropic support to maintain blood pressure if necessary. If pump
flow must be lowered or circulatory arrest is essential, thorough cerebral
cooling to deep hypothermic temperatures is mandatory; a pH-stat strategy may
make this easier, but an alpha-stat strategy may be better in those operations
that can be performed at moderate hypothermia. There is no evidence that the
available pulsatile pumps offer an advantage. Tissue oxygenation may reach
critical levels and a high hematocrit and oxygen tension may reduce the risk of
significant hypoxia. There is a risk of embolization in children, which can be
reduced with membrane oxygenators and careful monitoring; the role of arterial
filtration remains controversial. The only protective agent that can currently be
recommended is methylprednisolone to protect the spinal cord (e.g., in operations
on the aortic arch). Further studies are needed in this important area.
PMID- 9636260
TI - Current concepts in diagnosis and management of arrhythmias in infants and
children
PMID- 9636259
TI - Utility of intraoperative transesophageal echocardiography in the assessment of
residual cardiac defects.
AB - To investigate the accuracy of immediate postbypass transesophageal
echocardiography in the assessment of residual cardiac defects, we compared
intraoperative transesophageal echocardiograms with intra/postoperative data in
86 patients, aged 4 days to 30.7 years (median = 1.4 years), at risk for a total
of 174 postoperative lesions: right (n = 55) or left (n = 26) ventricular outflow
tract obstruction, ventricular septal defect (n = 65), aortic (n = 12) or mitral
regurgitation (n = 8), or mitral stenosis (n = 8). Accuracy of intraoperative
transesophageal echocardiography was evaluated based on comparison with (1)
immediate post-bypass left (n = 4) or right (n = 9) ventricular outflow tract
pressure gradients by pullback in the operating room, (2) direct surgical
inspection of residual ventricular septal defects (n = 3), (3) pulmonary artery
oxygen saturation (n = 49), (4) right ventricular outflow tract pullback gradient
(n = 24), and (5) transthoracic echocardiogram (n = 51) performed within 40 days
of surgery. The results indicate that intraoperative transesophageal
echocardiography agreed with intra/postoperative data in 87% of patients at risk
for right ventricular outflow tract obstruction, 96% at risk for left ventricular
outflow tract obstruction, 97% at risk for ventricular septal defect, and 100% at
risk for aortic regurgitation, mitral regurgitation, or mitral stenosis.
Significant residual lesions led to immediate surgical revision in 11 cases: 3
ventricular septal defects, 6 right and 2 left ventricular outflow tract
obstructions. Of these, intraoperative transesophageal echocardiography confirmed
and quantified suspected residual lesions in 7 and identified unsuspected lesions
in 4 cases. Immediate postbypass transesophageal echocardiography proved reliable
for assessing residual ventricular septal defect, mitral stenosis, and mitral or
aortic regurgitation. Although accurate for assessment of the left and right
ventricular outflow tracts in most patients, transesophageal echocardiography may
not reliably reflect the severity of obstruction in all cases.
PMID- 9636261
TI - Is surgical ligation of an accessory left superior vena cava always safe?
AB - In patients considered for bidirectional Glenn or Fontan procedures, the
association of left superior vena cava (LSVC) with ostial atresia of the coronary
sinus should be diagnosed preoperatively in order to avoid surgical division or
ligation of the LSVC and the negative effect of resulting coronary venous
hypertension on myocardial perfusion. This report discusses the angiographic and
hemodynamic features of LSVC when it is the only drainage route from a blind
coronary sinus. A retrograde flow in the LSVC seen by Doppler ultrasonography
should raise the suspicion of this diagnosis.
PMID- 9636262
TI - Fenestration of extracardiac fontan and reversal of protein-losing enteropathy:
case report.
AB - We describe a patient with protein-losing enteropathy who presented 6 months
after undergoing a modified Fontan operation. After failing to respond to medical
therapy, the Fontan tunnel was fenestrated by catheter intervention with
immediate improvement and resolution of hypoproteinemia and enteric protein loss.
PMID- 9636263
TI - Unusual longevity without surgical intervention in complete transposition of the
great arteries.
AB - A case of unusual longevity to the age of 58 years is reported for a female
patient with complete transposition of the great arteries. The association with a
wide atrial septal defect with intact interventricular septum may have
contributed to the long survival without surgery. Factors determining
intercirculatory mixing and systemic oxygen saturation may be the high pulmonary
flow, the location of the anatomic communication, sufficient hemoglobin
concentration to allow an adequate level of systemic resistance and recirculated
systemic flow, and the belated development of pulmonary vascular disease.
PMID- 9636264
TI - Double-outlet right ventricle (tetralogy of Fallot type) associated with
anomalous origin of the left coronary artery from the right pulmonary artery:
report of successful total repair in a 2-month-Old infant.
AB - The case reported herein demonstrates the rare association of double-outlet right
ventricle (tetralogy of Fallot type) with anomalous origin of the left coronary
artery from the pulmonary artery. It is the first reported successful total
surgical repair in an infant.
PMID- 9636265
TI - Development of superior vena cava to pulmonary vein fistulae following modified
Fontan operation: case report of a rare anomaly and embolization therapy.
AB - A patient with double inlet single ventricle, L-transposition of the great
arteries, and atrioventricular valve regurgitation developed progressive heart
failure necessitating modified Fontan operation at 16 months of age. The
procedure included replacement of the atrioventricular valve and pacemaker
insertion. Eight years following the operation, the patient developed progressive
cyanosis. Catheterization confirmed the presence of fistulae from the superior
vena cava and innominate vein to the pulmonary veins as the cause of cyanosis.
Coil embolization of several fistulae was performed successfully at
catheterization. Contributing factors for fistula formation in Fontan patients
are discussed, and therapy is reviewed.
PMID- 9636266
TI - Myocardial infarction in a 14-year-old girl, ten years after surgical correction
of congenital coronary artery fistula.
AB - Acute myocardial infarction developed in a 14-year-old girl, ten years after
surgical repair of a coronary artery fistula. Angiography revealed fresh thrombus
in the left anterior descending branch of the left coronary artery. The thrombus
probably developed in the residual cul-de-sac of the occluded fistula. A
procedure to abolish the cul-de-sac was then performed.
PMID- 9636267
TI - Surgical treatment of aortic root aneurysm related to Marfan syndrome in early
childhood.
AB - The prognosis of Marfan syndrome in both adult and pediatric patients is
primarily related to the cardiovascular complications. In infantile Marfan
syndrome, although involvement of the mitral valve is the most frequently
encountered cardiovascular lesion, the aortic root can be more worrisome because
of its excessive dilatation, leading to aortic insufficiency or dissection. If
the role of elective surgery is relatively well defined for adult patients, it is
still debated during childhood. We report two patients, aged 22 months and 5
years, each presenting an aortic root aneurysm related to Marfan syndrome, and
each treated with the Bentall procedure without specific age-related mortality or
morbidity. These two patients experienced normal growth and were free of any
complication for a follow-up period of 8 and 2 years, respectively. More than an
absolute value of the aortic root dimension, it is the conjunction of the rate of
progression of the aortic root dilatation, the degree and the duration of the
aortic valve regurgitation, and its resulting left ventricular dysfunction that
must be taken into consideration in choosing the surgical option.
PMID- 9636269
TI - From other journals
PMID- 9636268
TI - Transient hypertrophic cardiomyopathy in neonates.
PMID- 9636271
TI - Upcoming events in pediatric cardiology
PMID- 9636270
TI - Historical vignette: relief of right ventricular outflow tract obstruction.
PMID- 9636272
TI - HIV protease inhibitors head to market.
PMID- 9636273
TI - Recent advances in reproductive genetic technologies.
AB - New possibilities for the diagnosis and treatment of reproductive and genetic
disorders are becoming available as a result of a series of recent technical
advances. Intracytoplasmic sperm injection (ICSI) allows treatment of numerous
infertile men whose sperm cannot penetrate the egg to initiate fertilization.
Molecular genetic testing provides clients of reproductive age with additional
information that permits prevention of genetic diseases such as fragile X
syndrome, the leading cause of inherited mental retardation. Preimplantation
genetic testing (PGT) offers couples who carry genetic disorders the prospect of
having children with a greatly decreased risk of initiating a pregnancy involving
an affected individual. Flow-cytometric sperm separation offers a new, effective
approach for prevention of X-linked genetic disorders. Two major causes of
recurrent pregnancy loss (RPL) involve recurrent trisomies and immunological
disorders. Of the latter, 70% of studied populations of patients can attain live
births with simple treatment protocols. Maternal serum assays involving multiple
markers reduce both false positives and false negatives in detection of
trisomies. Despite these advances in research, many safe and effective methods of
diagnosis and treatment remain under-utilized in the clinical arena.
PMID- 9636274
TI - Design, expression, and initial characterization of MB1, a de novo protein
enriched in essential amino acids.
AB - Using recently emerging protein folding principles we have designed a protein
enriched in the essential amino acids methionine, threonine, lysine and leucine.
Our preliminary study of consensus residues (based on charge, hydrophobicity and
volume) of natural alpha-helical bundle proteins indicated that the residues M,
T, K, and L could be inserted in an alpha-helical bundle structure. We therefore
attempted to create a stable de novo protein, highly enriched in these essential
amino acids, that would adopt the alpha-helical bundle fold. The design process
was an iterative one. The consensus residues (based on the properties profile)
for bundle helices were found considering the four helices taken together,
helices I to IV individually, or only their N- and C-termini. Using these data,
the helices in our de novo protein were designed by inserting the residues M, T,
K and L as often as possible at positions where their volume, hydrophobicity and
charge match the consensus found in natural bundle helices. Short sequences of
strong turn formers were used to join the helices and adjust the predicted p1 to
7.7, while a number of local and global factors were used to refine our design.
Further, the sequence was checked to eliminate various known protease targets in
E. coli. The sequence of our de novo protein, MB1, is: MAT-EDMTDMMTTLFKTMQLLTK
SEPTA-MDEATKTATTMKNHLQNLMQK-TKNKE DMTDMATTYFKTMQLLTK-TEPSA-MDEATKTATTMKNHLQNLMQK
GVA+ ++ , where dashes separate long helices from short, turn forming linkers. A
gene coding for this protein was assembled from synthetic oligonucleotides, then
fused to the maltose binding protein gene under the control of a tac promoter.
The fusion protein was expressed in E. coli, purified and cleaved to yield
maltose binding protein and our de novo protein, MB1. MB1 was found to be
helical, to have the expected molecular weight (11 kDa) and the expected content
(57%) of the essential amino acids M, T, K and L.
PMID- 9636275
TI - Production of recombinant bovine enterokinase catalytic subunit in Escherichia
coli using the novel secretory fusion partner DsbA.
AB - Enterokinase (EK) is a heterodimeric serine protease which plays a key role in
initiating the proteolytic digestion cascade in the mammalian duodenum. The
enzyme acts by converting trypsinogen to trypsin via a highly specific cleavage
following the pentapeptide recognition sequence (Asp)4-Lys. This stringent site
specificity gives EK great potential as a fusion protein cleavage reagent.
Recently, a cDNA encoding the catalytic (light) chain of bovine enterokinase
(EKL) was identified, characterized, and transiently expressed in mammalian COS
cells. We report here the production of EKL in Escherichia coli by a novel
secretory expression system that utilizes E. coli DsbA protein as an N-terminal
fusion partner. The EKL cDNA was fused in-frame to the 3'-end of the coding
sequence for DsbA, with the two domains of the fusion protein separated by a
linker sequence encoding an enterokinase recognition site. Active, processed
recombinant EKL (rEKL) was generated from this fusion protein via an
autocatalytic cleavage reaction. The enzymatic properties of the bacterially
produced rEKL were indistinguishable from the previously described COS-derived
enzyme. Both forms of rEKL were capable of cleaving peptides, polypeptides and
trypsinogen with the same specificity exhibited by the native heterodimeric
enzyme purified from bovine duodena. Interestingly, rEKL activated trypsinogen
poorly relative to the native heterodimeric enzyme, but was superior in its
ability to cleave artificial fusion proteins containing the (Asp)4-Lys
recognition sequence.
PMID- 9636276
TI - A biotechnological method provides access to aggregation competent monomeric
Alzheimer's 1-42 residue amyloid peptide.
AB - Senile plaques, a neuropathological hallmark of Alzheimer's disease, consist
primarily of insoluble aggregates of beta-amyloid peptide (A beta). A 42-residue
peptide (A beta 1-42) appears to be the predominant form. In contrast to A beta 1
40, A beta 1-42 is characterized by its extreme tendency to aggregate into fibers
or precipitate. A tailored biotechnological method prevents aggregation of A beta
1-42 monomers during its production. The method is based on a protein tail fused
to the amino terminus of A beta. This tail leads to a high expression in E. coli,
and a histidine affinity tag facilitates purification. Selective cleavage of the
fusion tail is performed with cyanogen bromide by immobilizing the fusion protein
on a reversed phase chromatography column. Cleavage then occurs only at the
methionine positioned at the designed site but not at the methionine contained in
the membrane anchor sequence of A beta. Furthermore, immobilization prevents
aggregation of cleaved A beta. Elution from the HPLC column and all succeeding
purification steps are optimized to preserve A beta 1-42 as a monomer. Solutions
of monomeric A beta 1-42 spontaneously aggregate into fibers within hours. This
permits the investigation of the transition of monomers into fibers and the
correlation of physico-chemical properties with biological activities. Mutations
of A beta 1-42 at position 35 influence the aggregation properties. Wild-type A
beta 1-42 with methionine at position 35 has similar properties as A beta with a
methionine sulfoxide residue. The fiber formation tendency, however, is reduced
when position 35 is occupied by a glutamine, serine, leucine, or a glutamic acid
residue.
PMID- 9636277
TI - Double replacement gene targeting for the production of a series of mouse strains
with different prion protein gene alterations.
AB - We have developed a double replacement gene targeting strategy which enables the
production of a series of mouse strains bearing different subtle alterations to
endogenous genes. This is a two-step process in which a region of the gene of
interest is first replaced with a selectable marker to produce an inactivated
allele, which is then re-targeted with a second vector to reconstruct the
inactivated allele, concomitantly introducing an engineered mutation. Five
independent embryonic stem cell lines have been produced bearing different
targeted alterations to the prion protein gene, including one which raises the
level of expression. We have constructed mice bearing the codon 101 proline to
leucine substitution linked to the human familial prion disease, Gerstmann
Straussler-Scheinker syndrome. We anticipate that this procedure will have
applications to the study of human inherited diseases and the development of
therapies.
PMID- 9636278
TI - Transovarian transmission of a foreign gene in the silkworm, Bombyx mori, by
Autographa californica nuclear polyhedrosis virus.
AB - We introduced a firefly luciferase gene, expressed under control of Drosophila
heat shock protein gene promoter, into Autographa californica nuclear
polyhedrosis virus (AcNPV). When the 5th instar larvae of the silkworm, Bombyx
mori, were inoculated with the recombinant virus, luciferase activities were
detected in the virus-infected larvae and pupae, and in the newly hatched larvae
of the next generation. PCR amplification and Southern blot hybridization
analysis demonstrated that the luciferase gene was transmitted through at least
the F2 generation. In addition, the V-cathepsin gene, encoding a cysteine
protease of AcNPV, was also detected in the DNA of all individuals of the F2
generation. These results show that AcNPV can be utilized as vector for the
transovarian transmission of foreign genes in the silkworm.
PMID- 9636279
TI - Using viral genes to fight disease.
PMID- 9636280
TI - Obesity: where less is more.
PMID- 9636281
TI - Eukaryotic virus display: engineering the major surface glycoprotein of the
Autographa californica nuclear polyhedrosis virus (AcNPV) for the presentation of
foreign proteins on the virus surface.
AB - We describe the development of the baculovirus Autographa californica nuclear
polyhedrosis virus (AcNPV) as a vector for the display of distinct proteins on
the viral surface in a manner that is analogous to the established bacterial
"phage display" systems. As a model system, the marker gene encoding the 26kDa
protein glutathione-S-transferase (GST) was used to construct several fusions
with the major baculovirus glycoprotein gp64 gene. Following expression in
Spodoptera frugiperda (Sf9) cells, the yield and cellular distribution of each
GST-gp64 protein was assessed by Western blot of both cell and supernatant
fractions. One fusion, in which GST was inserted between the leader peptide and
the nature protein, was found to be efficiently secreted into the cell medium. In
the context of expression of the full length gp64, the hybrid GST-gp64 was shown
by immunogold labelling to be incorporated onto the virion surface. In addition,
the affinity purification of the soluble transmembrane gp64-GST fusion protein
resulted in the co-purification of wild type gp64 suggesting that co
oligomerization of the GST-tagged fusion and the wild type molecule was the basis
for virion incorporation. The HIV major surface glycoprotein, gp120 was also
efficiently displayed in functional form on the viral surface following fusion to
the amino terminus of gp64. A general expression vector, pAcSurf-2, was
constructed in which multiple cloning sites were positioned in-phase between the
gp64 signal sequence and the sequence encoding the mature protein under the
control of the polyhedrin promoter.
PMID- 9636282
TI - "Horizontal" gene transfer from a transgenic potato line to a bacterial pathogen
(Erwinia chrysanthemi) occurs--if at all--at an extremely low frequency.
AB - The frequency of possible "horizontal" gene transfer between a plant and a
tightly associated bacterial pathogen was studied in a model system consisting of
transgenic Solanum tuberosum, containing a beta-lactamase gene linked to a pBR322
origin of replication, and Erwinia chrysanthemi. This experimental system offers
optimal conditions for the detection of possible horizontal gene transfer events,
even when they occur at very low frequency. Horizontal gene transfer was not
detected under conditions mimicking a "natural" infection. The gradual, stepwise
alteration of artificial, positive control conditions to idealized natural
conditions, however, allowed the characterization of factors that affected gene
transfer, and revealed a gradual decrease of the gene transfer frequency from 6.3
x 10(-2) under optimal control conditions to a calculated 2.0 x 10(-17) under
idealized natural conditions. These data, in combination with other published
studies, argue that horizontal gene transfer is so rare as to be essentially
irrelevant to any realistic assessment of the risk involved in release
experiments involving transgenic plants.
PMID- 9636283
TI - The intracellular domain of the rabbit prolactin receptor is able to promote the
secretion of a passenger protein via an unusual secretory pathway in lepidopteran
cells.
AB - We have previously shown that the intracellular domain of the rabbit prolactin
receptor (rbPRL-R), lacking typical signal sequences, was very efficiently
secreted into the culture medium when expressed in the baculovirus-insect cell
system. We have sought to take advantage of this characteristic for secreting
cytoplasmic or nuclear proteins. We have constructed a series of recombinant
viruses expressing a foreign gene product fused to the intracellular domain of
rbPRL-R. Two passenger genes were used, one encoding a cytoplasmic protein
(cyclin B) and the other a nuclear protein (cyclin A). The intracellular domain
of rbPRL-R was able to promote the export of these two chimeric proteins with a
very high efficiency. This new system should prove useful for secretion of
proteins which do not require the post-translational modifications of the
classical secretory pathway to be fully active.
PMID- 9636284
TI - Human stress protein hsp70: overexpression in E coli, purification and
characterization.
AB - The gene encoding the stress-inducible member of human heat shock protein hsp70,
was expressed in E. coli using the bacteriophage T7 RNA polymerase-based gene
expression system. Recombinant hsp70 (R-hsp70) was purified from inclusion bodies
after solubilization and refolding, using a combination of ATP-agarose affinity
chromatography and ion-exchange chromatography. R-hsp70 was shown to be monomeric
and free of its structurally similar E. coli counterpart, DnaK. In addition, R
hsp70 is functional as demonstrated by its ability to bind to peptides and to
ATP. The availability of pure, correctly folded R-hsp70 in sufficient quantity
will assist in the structural and functional characterization of hsp70.
Furthermore, an understanding of the cytoprotective function of hsp70 and its
role in immune responses during infections will be facilitated by the
availability of pure R-hsp70.
PMID- 9636285
TI - Redox state of single chain Fv fragments targeted to the endoplasmic reticulum,
cytosol and mitochondria.
AB - In this paper we have engineered the targeting of ScFv fragments to mitochondria
and demonstrated that this can occur efficiently. This extends the range of
subcellular compartments where antibody domains can be targeted in order to
interfere with the action of the corresponding antigen. Moreover, we have
compared the redox state of ScFv fragments targeted to the secretory compartment,
the cytosol and the mitochondria, and demonstrated that cysteine residues in ScFv
targeted to the secretory compartments and to the mitochondria are oxidized. On
the contrary, cytosolic antibody domains are expressed in a reduced state, which
is probably the reason for their lower expression levels. These pitfalls,
however, do not prevent their successful utilization for intracellular
immunization.
PMID- 9636286
TI - Mammalian cell technology: secretion on demand.
PMID- 9636287
TI - Pig hearts in the clinic next year?
PMID- 9636288
TI - Pinning down a moving target: a standard HIV.
PMID- 9636289
TI - Nervous excitement over neurotrophic factors.
PMID- 9636290
TI - Biotechnology of breadmaking: unraveling and manipulating the multi-protein
gluten complex.
AB - Breadmaking is one of humankind's oldest technologies, being established some
4,000 years ago. The ability to make leavened bread depends largely on the visco
elastic properties conferred to wheat doughs by the gluten proteins. These allow
the entrapment of carbon dioxide released by the yeast, giving rise to a light
porous structure. One group of gluten proteins, the high molecular weight (HMW)
subunits, are largely responsible for gluten elasticity, and variation in their
amount and composition is associated with differences in elasticity (and hence
quality) between various types of wheat. These proteins form elastomeric polymers
stabilized by inter-chain disulphide bonds, and detailed studies of their
structures have led to models for the mechanism of elasticity. This work has also
provided a basis for direct improvement of wheat quality by transformation with
additional HMW subunit genes.
PMID- 9636291
TI - Regulated secretion of prolactin by the mouse insulinoma cell line beta TC-3.
AB - Our aim is to use cultured cells capable of regulated protein secretion for the
production of recombinant proteins that require particular types of post
translational modifications. Here we have generated a stable transfected beta TC
3 cell line, beta TC-IPR9, that secretes high levels of recombinant prolactin.
Transfected cells synthesize both the 27 kDa glycosylated and a 23 kDa
nonglycosylated prolactin; the 23 kDa nonglycosylated species was secreted
preferentially when cells were placed in secretion medium containing
isobutylmethylxanthine (IBMX) and high concentrations of glucose, K+, and Ca2+.
When the cells were cultured in medium containing low concentrations of glucose,
K+, and Ca2+, most of the prolactin and insulin were not secreted; much of the
prolactin was proteolytically converted to a 16 kDa form. Within the first 30
minutes after transferring the cells to medium containing secretagogues there was
a 20-fold increase in the rate of secretion of prolactin; all of the 16 kDa
species was secreted. The recombinant cells could be cycled several times between
medium in which prolactin was biosynthesized and medium in which it was secreted.
Preferential secretion of proteolytically processed prolactin in a medium without
contaminating proteins offers an example of the advantage of this technology for
production of other recombinant proteins.
PMID- 9636292
TI - Engineered chimeric streptavidin tetramers as novel tools for bioseparations and
drug delivery.
AB - We report the construction of chimeric streptavidin tetramers that are composed
of subunits of both wild-type (WT) streptavidin and genetically-engineered
streptavidin variants designed for enhanced bioseparation and drug delivery
performance. Subunit mixing is accomplished by guanidine thiocyanateinduced
denaturation of an equimolar mixture of WT streptavidin and the respective site
directed mutant, followed by renaturation and reassociation of mixed tetramers.
In the first example, we demonstrate the mixing of WT subunits with an Asn49Cys
(N49C) mutant. The WT/n49C tetramers can be used for site-specific and
stoichiometric attachment of therapeutics/imaging agents or targeting proteins
through the genetically-engineered thiol while retaining unhindered access to
biotin-binding at the WT subunits. Second, we demonstrate that the His127Cys
mutation (H127C) results in a streptavidin mutant that forms a disulfide-linked
dimer under non-reducing conditions. Mixing of H127C and WT streptavidin subunits
results in chimeric tetramers where both the stoichiometry (WT:H127C::1:1) and
subunit architecture is controlled by the unique disulfide bridge engineered into
H127C. In the third example, WT subunits were mixed with the subunits of a site
directed mutant, Trp120Ala (W120A), which displays a biotin dissociation constant
that is enhanced by more than 10(4) compared to WT streptavidin. The W120 biotin
binding affinity is sufficiently high (Ka approximately equal to 10(7) M-1) to
immobilize the mutant on a biotinagarose affinity chromatography column, but the
engineered off-rate allows for facile elution with excess biotin at physiological
pH, whereas WT streptavidin is irreversibly immobilized on the column. We
demonstrate that the purified WT/W120A chimeric tetramers combine the advantages
of both subunits, allowing for irreversible immobilization of biotinylated
targets at the WT subunit, while retaining the reversible separation capabilities
of the W120A subunits via biotin-agarose affinity chromatography.
PMID- 9636293
TI - Transdermal delivery of heparin by skin electroporation.
AB - Therapeutic uses of compounds produced by biotechnology are presently limited by
the lack of noninvasive methods for continuous administration of biologically
active macromolecules. Transdermal delivery would be an attractive solution,
except macromolecules have not previously been delivered clinically across human
skin at therapeutic rates. To increase transport of a highly-charged
macromolecule (heparin), high-voltage pulses believed to cause electroporation
were applied to skin. Using this approach, transdermal heparin transport across
human skin in vitro occurred at therapeutic rates (100-500 micrograms/cm2h),
reported to be sufficient for systemic anticoagulation. In contrast, fluxes
caused by low-voltage iontophoresis having the same time-averaged current were an
order of magnitude lower. Heparin transported across the skin was biologically
active, but with only one eighth the anticoagulant activity of heparin in the
donor compartment due to preferential transport of small (less active) heparin
molecules. Flux, activity, and transport number data together suggest that high
voltage pulsing creates transient changes in skin microstructure which do not
occur during iontophoresis. Safety issues are discussed.
PMID- 9636294
TI - A high capacity assay for inhibitors of human papillomavirus DNA replication.
AB - The discovery of antiviral compounds against human papillomaviruses (HPV) has
been hindered by the difficulties in culturing virus in vitro or assaying stable
HPV DNA replication. However, plasmids containing the HPV replication origin
replicate transiently upon co-transfection with HPV E1 and E2 expression vectors.
We have adapted this assay using secreted alkaline phosphatase (SAP) as a
reporter for rapid analysis of DNA copy number. Use of the SV40 early promoter in
controlling SAP expression was critical in ensuring both a strong signal and copy
number dependence: the stronger beta-actin promotor inhibited replication, while
the weaker SV40 late promoter yielded very low levels of SAP. The precise
configuration of the E1 and E2 expression vectors also was critical, most pre
existing vectors did not support efficient replication and SAP secretion. The
extent of DNA replication and SAP secretion were both proportional to the amount
of E1/E2 vector used in transfections; under optimal conditions SAP increased 100
fold during replication. The assay has been developed for compound screening in
96-well plates and several inhibitors have been identified. Quantitative Southern
blot analysis has shown that most of these inhibit HPV DNA replication rather
than SAP accumulation or activity, and several are under test in models of viral
replication. The assay also provides a rapid system for functional analysis of
the HPV E1, E2 genes and the replication origin.
PMID- 9636295
TI - A generic method for expression and use of "tagged" soluble versions of cell
surface receptors.
AB - A general method for expression, purification, immobilization, detection and
radiolabeling of extracellular domains (ECD) of type I membrane proteins. The
type I interleukin-1 receptor (IL-1RtI), the alpha-subunit of interleukin-2
receptor (IL-2R alpha) and E-selectin are used as illustrative examples of cell
surface receptors. DNA encoding the ECD of the proteins are fused at their 3' end
to a chimeric DNA which serves to generically "tag" the recombinant ECD. The
resulting fusion protein contains a substrate sequence for protein kinase-A (PKA)
adjacent to the signal sequence from human placental alkaline phosphatase (HPAP),
The HPAP signal sequence directs the formation of the phosphatidylinositol-glycan
(PI-G) anchorage of the protein at the cell surface. When these chimeric genes
are expressed in CHO cells, the ECDs are detected on the cell surface and can be
released by treatment with phosphatidylinositol-specific phospholipase-C (PI
PLC). Based on protein processing known to occur for native HPAP, twenty amino
acids from the HPAP signal sequence remain at the C-terminus of the ECD. A high
affinity monoclonal antibody was generated against this common epitope. This
antibody can be used to detect, purify and immobilize the ECDs. In addition, the
ECDs can be radiolabeled with 32P by treatment with PKA and maintain the ability
to bind their natural ligands. This "tagging" method has been successfully
applied to many other type I proteins which serve as cell surface receptors.
PMID- 9636296
TI - Rapid assay of phage-derived recombinant human fabs as bispecific antibodies.
AB - Specific anti-tumor and anti-viral activities can be conferred on lymphocytic and
myeloid effector cells by retargeting them with bispecific antibodies. These are
antibodies which possess an anti-target binding region and a region capable of
binding specific effector cell surface markers. For the rapid evaluation of
recombinant human Fabs as bispecific antibodies, we have constructed a vector
that allows for the conversion of Fabs into protein A fusion proteins. These can
be used to generate bispecific antibodies when complexed to appropriate anti
effector cell immunoglobulins. As a model system, a protein A fusion derivative
of a human recombinant anti-herpes simplex virus (HSV) Fab was constructed and
complexed to OKT3, a T cell-activating antibody specific for CD3. This complex
reduced HSV-2 yields in infected cells by about three logs relative to controls
when incubated on HSV-2-infected cell monolayers in the presence of IL-2
activated lymphocytes. The system described allows for the rapid evaluation of
recombinant human Fabs as bispecific antibodies for therapeutic applications. In
addition, Fab-protein A fusion proteins can be used in ELISA and other immuno
assays with increased sensitivity.
PMID- 9636297
TI - Expression of the human muscarinic receptor gene m2 in Dictyostelium discoideum.
AB - We have expressed a functional human muscarinic M2 receptor, under the control of
the homologous discoidin I gamma promoter, in the cellular slime mold
Dictyostelium discoideum. The use of a contact site A leader peptide ensured
insertion of the newly synthesized receptor protein into the plasma membrane. Due
to the characteristics of the discoidin I gamma promoter, the M2 receptor is
expressed during late growth and early development. The heterologously expressed
M2 receptors show binding characteristics similar to authentic receptors.
Membranes as well as whole cells can be used in ligand binding assays.
PMID- 9636298
TI - Expression of active, secreted human prostate-specific antigen by recombinant
baculovirus-infected insect cells on a pilot-scale.
AB - We have expressed human prostate-specific antigen (PSA) on a pilot-scale in
Spodoptera frugiperda Sf9 insect cells using recombinant baculovirus system.
Infected cells secreted PSA into culture medium at a concentration of 2-4 mg per
liter. PSA was expressed both in active and inactive forms which were separated
in a final purification step using cation-exchange chromatography eluted with a
low salt gradient. The N-terminus of active PSA was correctly cleaved; two amino
acids of the propeptide remained, however, at the N-terminus of the inactive PSA.
Purified recombinant PSA showed a chymotrypsin-like activity with the synthetic
substrate MeO-Suc-Arg-Pro-Tyr-pNA, but did not have a trypsin-like activity when
Pro-Phe-Arg-pNA was used. The molecular mass of active PSA was 31.0 kDa in
reduced SDS-PAGE, 26.0 kDa in nonreduced SDS-PAGE and 26.5 kDa in ion spray mass
spectrometry. The active protein formed complexes with alpha 1-antichymotrypsin
(ACT) and alpha 2-macroglobulin (alpha 2M) in vitro similar to the commercial PSA
purified from human seminal fluid.
PMID- 9636299
TI - A new use for the mycoprotein organism.
PMID- 9636300
TI - The many faces of IL-12.
PMID- 9636301
TI - The cost of delivering drugs without needles.
PMID- 9636302
TI - Therapeutic applications of heat shock proteins.
PMID- 9636303
TI - Capillary electrophoresis-based immunoassays.
PMID- 9636304
TI - Mammary gland expression of transgenes and the potential for altering the
properties of milk.
AB - Transgenic animals are a useful in vivo experimental model for assessing the
ability and impact of foreign gene expression in a biological system. Transgenic
mice are most commonly used, while transgenic sheep, goats, pigs and cows have
also been developed for specific, "applied" purposes. Most of the work directed
at targeting expression of transgenes to the mammary gland of an animal, by using
a milk gene promoter, has been with the intent of either studying promoter
function or recovering the desired protein from the milk. Transgenic technology
can also be used to alter the functional and physical properties of milk
resulting in novel manufacturing properties. The properties of milk have been
altered by adding a new protein with the aim of improving the milk, not of
recovering the protein for other uses.
PMID- 9636306
TI - The yeast tribrid system--genetic detection of trans-phosphorylated ITAM-SH2
interactions.
AB - Protein-protein interactions are often dependent on the post-translational
modification of one component of a complex. To facilitate the study of these
interactions in signal transduction, we have developed the yeast tribrid system,
a modification of the yeast two-hybrid system. We demonstrate that the
interactions are dependent upon the presence of a tyrosine kinase, an SH2 domain
and a tyrosine containing substrate. Using the gamma subunit of the high-affinity
IgE receptor, Fc epsilon RI, this approach has been used to isolate a novel SH2
containing family member. The mRNA encoding this novel protein is differentially
expressed in rat tissues. The yeast tribrid system can be readily adapted for the
characterization of novel tyrosine kinases or substrates, as well as the study of
protein-protein interactions which involve other post-translational
modifications.
PMID- 9636307
TI - Fusarium graminearum A 3/5 as a novel host for heterologous protein production.
AB - We describe a novel fungal expression system which utilizes the Quorn myco
protein fungus Fusarium graminearum A 3/5. A transformation system was developed
for F. graminearum and was used to introduce the coding and regulatory regions of
a trypsin gene from Fusarium oxysporum. The protein was efficiently expressed,
processed and secreted by the recombinant host strain. In addition, the promoter
and terminator of the F. oxysporum trypsin gene have been successfully utilized
to drive the expression of a cellulase gene from Scytalidium thermophilum and a
lipase gene from Thermomyces lanuginosus in F. graminearum.
PMID- 9636308
TI - Expression of the rabies virus glycoprotein in transgenic tomatoes.
AB - We have engineered tomato plants (Lycopersicon esculentum Mill var. UC82b) to
express a gene for the glycoprotein (G-protein), which coats the outer surface of
the rabies virus. The recombinant constructs contained the G-protein gene from
the ERA strain of rabies virus, including the signal peptide, under the control
of the 35S promoter of cauliflower mosaic virus. Plants were transformed by
Agrobacterium tumefaciens-mediated transformation of cotyledons and tissue
culture on selective media. PCR confirmed the presence of the G-protein gene in
plants surviving selection. Northern blot analysis indicated that RNA of the
appropriate molecular weight was produced in both leaves and fruit of the
transgenic plants. The recombinant G-protein was immunoprecipitated and detected
by Western blot from leaves and fruit using different antisera. The G-protein
expressed in tomato appeared as two distinct bands with apparent molecular mass
of 62 and 60 kDa as compared to the 66 kDa observed for G-protein from virus
grown in BHK cells. Electron microscopy of leaf tissue using immunogold-labeling
and antisera specific for rabies G-protein showed localization of the G-protein
to the Golgi bodies, vesicles, plasmalemma and cell walls of vascular parenchyma
cells. In light of our previous demonstration that orally administered rabies G
protein from the same ERA strain elicits protective immunity in animals, these
transgenic plants should provide a valuable tool for the development of edible
oral vaccines.
PMID- 9636309
TI - Preparative scale purification of recombinant proteins to clinical grade by
isotachophoresis.
AB - An electrophoretic procedure based on isotachophoresis has been developed for
protein purification on a preparative scale in the 10 to 500 mg range. The system
is simple, uses well understood physical properties, does not need ampholyte
spacers and is able to produce sterile products of clinical grade. We demonstrate
the applicability of this apparatus for the purification of denatured recombinant
proteins and complex mixtures of proteins. The system may also be used for both
cationic and anionic purification of proteins in their native form. The system is
scalable from analytical to preparative protein loads at consistently high
protein yields and purity levels. Total protein loads may vary as much as 1000
fold with the use of interchangeable columns of varying diameter and constant
length. At both preparative and analytical scales concentration of products at
greater than 20 mg/ml are obtainable. Toxicological considerations are addressed
with assays for endotoxin, acrylamide and SDS concentrations, as well as the
prevention of covalent protein modification.
PMID- 9636310
TI - Therapeutic peptides: the devil is in the details.
PMID- 9636311
TI - Biotechnology and new integrated pest management approaches.
AB - Area-wide pest management technologies will take on new appearances as the drive
to eliminate and/or greatly reduce the use of chemical pesticides increases. The
use of genetically altered insects has the most potential for successfully
displacing certain pesticides, although the development of genetic engineering
technologies for agricultural pest species is still in its infancy.
Transformation vectors need to be developed as do transformation methodologies.
Here we report the possibility of developing an interspecies vector and discuss
ways in which such a vector could be used successfully in an integrated pest
management system. If such an approach were developed, it could be utilized with
other alternative methods, thereby providing a safe, ecologically sound means of
controlling insect pests without damaging the agricultural economy.
PMID- 9636312
TI - Homologous expression and purification of mutants of an essential protein by
reverse epitope-tagging.
AB - Purification of mutant enzymes is a prime requirement of biophysical and
biochemical studies. Our investigations on the essential Escherichia coli enzyme
glutaminyl-tRNA synthetase demand mutant enzymes free of any wild-type protein
contamination. However, as it is not possible to express noncomplementing mutant
enzymes in an E. coli glnS-deletion strain, we developed a novel strategy to
address these problems. Instead of following the common tactic of epitope-tagging
the mutant protein of interest on an extrachromosomal genetic element, we fused a
reporter epitope to the 5' end of the chromosomal glnS-gene copy: this is
referred to as 'reverse epitope-tagging.' The corresponding strain, E. coli
HAPPY101, displays a normal phenotype, and glutaminyl-tRNA synthetase is
exclusively present as an epitope-tagged form in cell-free extracts. Here we
report the use of E. coli HAPPY101 to express and purify a number of mutant
glutaminyl-tRNA synthetases independently of their enzymatic activity. In this
process, epitope-tagged wild-type protein is readily separated from mutant
enzymes by conventional chromatographic methods. In addition, the absence of wild
type can be monitored by immunodetection using a monoclonal antibody specific for
the epitope. The strategy described here for expression and purification of an
essential enzyme is not restricted to glutaminyl-tRNA synthetase and should be
applicable to any essential enzyme that retains sufficient activity to sustain
growth following reverse epitope-tagging.
PMID- 9636313
TI - From proteins to proteomes: large scale protein identification by two-dimensional
electrophoresis and amino acid analysis.
AB - Separation and identification of proteins by two-dimensional (2-D)
electrophoresis can be used for protein-based gene expression analysis. In this
report single protein spots, from polyvinylidene difluoride blots of
micropreparative E. coli 2-D gels, were rapidly and economically identified by
matching their amino acid composition, estimated pI and molecular weight against
all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2
D map were analyzed and identities assigned. Three of the proteins were unknown.
By protein sequencing analysis, 20 of the 27 proteins were correctly identified.
Importantly, correct identifications showed unambiguous "correct" score patterns.
While incorrect protein identifications also showed distinctive score patterns,
indicating that protein must be identified by other means. These techniques allow
large-scale screening of the protein complement of simple organisms, or tissues
in normal and disease states. The computer program described here is accessible
via the World Wide Web at URL address (http:@expasy.hcuge.ch/).
PMID- 9636314
TI - Characterization of human plasma glycoproteins separated by two-dimensional gel
electrophoresis.
AB - Purification of protein isoforms for the characterization of post-translational
modifications, such as glycosylation, can be laborious and demanding. We report a
means of determining monosaccharide composition and the identity of glycoproteins
from a single spot on a two-dimensional (2-D) gel. The sensitivity of the method
depends on the degree of glycosylation of the protein. We show that bovine fetuin
can be analyzed and identified at the level of 100 pmol. 2-D reference maps
enable quick identification of glycoprotein isoforms, and the nature of
glycosylation differences. Human sera glycoforms were isolated by
micropreparative 2-D PAGE using a narrow-range immobilized pH gradient. Single
spots excised from one polyvinylidene difluoride blot of a 2-D gel were used
sequentially for sialic acid analysis, neutral and amino sugar analysis, and
finally amino acid analysis. The glycosylation variations in isoforms of human
fetuin and alpha-1-antitrypsin were determined. The amino acid composition, in
conjunction with protein pI and MW, successfully identified the glycoproteins.
PMID- 9636315
TI - Transplanting two unique beta-glucanase catalytic activities into one
multienzyme, which forms glucose.
AB - Endo cellulases of plant pathogenic erwinias degrade cellulose as well as the
cellulosic domains of barley (1-3,1-4)-beta-glucan. Depolymerization of the
latter substrate is mainly caused by (1-3,1-4)-beta-glucanases, which hydrolyze
(1-4)-beta glycosidic linkages adjacent to (1-3)-beta linkages. To construct an
enzyme for efficient degradation of barley (1-3,1-4)-beta-glucan, the sequence
encoding the catalytic domain and interdomain linker of the cellulase from
Erwinia carotovora subspecies atroseptica was fused to that for the heat stable
Bacillus hybrid, H(A12-M) delta Y13 (1-3,1-4)-beta glucanase. The chimeric enzyme
secreted from Escherichia coli cells did not remain covalently assembled as
judged by SDS-PAGE. However, the glycosylated and intact enzyme (denoted CELGLU)
is secreted from the yeast Pichia pastoris. CELGLU exhibits both cellulase and (1
3,1-4)-beta-glucanase catalytic activities, and was accordingly classified a true
multienzyme. HPLC and NMR analyses revealed that among the products from CELGLU,
di- and trimeric oligosaccharides were identical to those produced by the
parental cellulase. Tetrameric oligosaccharides, derived from the (1-3,1-4)-beta
glucanase activity of CELGLU, were further degraded by the cellulase moiety to
yield glucose and trimers. Compared with the parental enzymes, CELGLU exhibits
substantially higher Vmax for degradation of both soluble cellulose and barley (1
3,1-4)-beta-glucan. These findings point to construction of multienzymes as an
effective approach for engineering enzymes with novel characteristics.
PMID- 9636316
TI - Production of a recombinant bovine enterokinase catalytic subunit in the
methylotrophic yeast Pichia pastoris.
AB - We describe the heterologous expression of a 26.3 kD protein containing the
catalytic domain of bovine enterokinase (EKL) in the methylotrophic yeast Pichia
pastoris. A highly active protein is secreted and glycosylated, and it has the
native amino-terminus of EKL. The cDNA encoding EKL was cloned with the KEX2
protease cleavage site following the alpha mating factor prepro secretion signal
from Saccharomyces cerevisiae. The secreted EKL was easily purified from the few
native proteins found in the P. pastoris fermentation supernatant, using ion
exchange and affinity chromatography. The yield of the purified EKL was 6.3 mg
per liter of fermentation culture. This is significantly higher than previous
reports of expressions in E. coli and COS cells. The ability of this highly
specific protease to cleave immediately after the carboxyl-terminal residue of
the (Asp)4-Lys recognition sequence allows regeneration of native amino-terminal
residues of recombinant proteins. Its application is demonstrated by the removal
of thioredoxin (TrxA), and polyhistidine fusion partners from proteins of
interest.
PMID- 9636317
TI - Development of an expression strategy using a lytic phage to trigger explosive
plasmid amplification and gene expression.
AB - A novel plasmid-based expression strategy, exploiting two features of lytic
bacteriophages, was developed in Lactococcus lactis. Components of this system
include a phage origin of replication and phage expression signals, which were
induced to high efficiency upon phage infection of the host. Phage-specific
expression signals were cloned from phi 31 in a promoter-screening strategy using
the lacZ gene from Streptococcus thermophilus. One clone exhibited a significant
induction in beta-galactosidase production and concomitant increase in lacZ mRNA
during the phi 31 infection cycle of the host. Molecular characterization of the
cloned insert revealed 888 bp positioned near the phi 31 cos site. Primer
extension analysis showed that transcription was induced approximately 20 min
following phi 31 infection at four points, apparently organized in two sets of
tandem promoters on the cloned phage insert. One of these middle phage promoters
also showed a basal level of activity prior to phage infection. The phi 31
promoter lacZ cassette was cloned into a low-copy-number vector plasmid
containing the phi 31 origin of replication (ori31) and the resulting low-copy
number plasmid exhibited negligible beta-galactosidase production in L. lactis.
However, > 2,000 units were detected following a deliberate infection with phi
31. A control expression plasmid without ori31 could only be induced to 85 units.
The combination of these phage-inducible expression signals together with ori31
functioned synergistically to drive rapid and high efficiency expression of a
heterologous gene in L. lactis.
PMID- 9636318
TI - Catalytical potency of beta-glucosidase from the extremophile Pyrococcus furiosus
in glucoconjugate synthesis.
AB - The extremely thermostable wild type and recombinant beta-glucosidases, from
Pyrococcus furiosus, served as catalysts for the biotransformation of new
glucoconjugates at elevated temperatures. In conversion experiments using the
transglucosylation approach, the free or immobilized enzyme accepted primary and
even tertiary organic alcohols, as well as primary and secondary artificial
organosilicon alcohols, as aglycones. Cellobiose served as the glucose donor. The
products obtained were purified by liquid chromatography and analyzed. Using beta
glucosidase a wide variety of products were synthesized. Due to the very broad
structural diversity of the aglycones linked to the 1-beta-O-D-glucose, this beta
glucosidase seems to be a useful biocatalyst for regio- and stereoselective sugar
derivative synthesis.
PMID- 9636319
TI - Transgenic Indica rice breeding line IR58 expressing a synthetic cryIA(b) gene
from Bacillus thuringiensis provides effective insect pest control.
AB - The Indica rice breeding line IR58 was transformed by particle bombardment with a
truncated version of a synthetic cryIA(b) gene from Bacillus thuringiensis. This
gene is expressed under control of the CaMV 35S promoter and allows efficient
production of the lepidopteran specific delta-endotoxin. R0, R1 and R2 generation
plants displayed a significant insecticidal effect on several lepidopterous
insect pests. Feeding studies showed mortality rates of up to 100% for two of the
most destructive insect pests of rice in Asia, the yellow stem borer (Scirpophaga
incertulas) and the striped stem borer (Chilo suppressalis), and feeding
inhibition of the two leaffolder species Cnaphalocrocis medinalis and Marasmia
patnalis. Introduction of stem borer resistance into the germplasm of an Indica
rice breeding line now makes this agronomically important trait available for
conventional rice breeding programs.
PMID- 9636320
TI - Targeting gene expression to the wool follicle in transgenic sheep.
AB - To establish the feasibility of overexpressing foreign genes in the wool
follicle, transgenic sheep were produced by pronuclear microinjection of a DNA
construct consisting of a mouse ultrahigh-sulfur keratin promoter linked to the
bacterial chloramphenicol acetyl transferase (CAT) gene. Four of 31 lambs born
were transgenic. The overall efficiency of transgenesis was 1.1% of zygotes
injected and transferred. Two transgenic rams were mated to nontransgenic ewes,
and both transmitted the gene to their offspring in Mendelian fashion. CAT
expression was found in the skin of one G0 ram and in 9 out of 26 transgenic G1
progeny. Two G1 lambs were sacrificed to study tissue specificity. Both had high
levels of expression in skin but One had high expression in spleen and kidney
with lower levels of expression in lung; the other had low expression in spleen,
lung, and muscle. In situ hybridization demonstrated that transgene expression in
the skin was confined to the keratogenous zone of the wool follicle cortex.
Expression of CAT activity in skin was correlated with diet-induced or seasonal
changes in the rate of wool growth. This keratin promoter appears useful for
overexpressing factors in the wool follicle that might influence wool production
or properties.
PMID- 9636321
TI - Improved wool production in transgenic sheep expressing insulin-like growth
factor 1.
AB - Transgenic sheep were produced by pronuclear microinjection with a mouse ultra
high-sulfur keratin promoter linked to an ovine insulin-like growth factor 1
(IGF1) cDNA. Five transgenic lambs resulted from the microinjection of 591
embryos; one male and one female showed IGF1 expression in the skin. A progeny
test of the ram was carried out by matings to 43 non-transgenic ewes. Of 85 lambs
born, 43 (50.6%) were transgenic. At yearling shearing (approximately 14 months
of age), clean fleece weight was on average 6.2% greater in transgenic animals
than in their non-transgenic half-sibs, with a greater effect in males (9.2%)
than females (3.4%). Transgenics showed a small but significant increase in bulk,
but male transgenics had a lower staple strength than female transgenics and non
transgenics which did not differ significantly. There were no significant
differences in fiber diameter, medullation, and hogget body weight. To our
knowledge this is the first reported improvement in a production trait by genetic
engineering of a farm animal without adverse effects on health or reproduction.
PMID- 9636322
TI - Restricting the dispersal of recombinant DNA: design of a contained biological
catalyst.
AB - To restrict horizontal gene spread and, thus, create organisms whose behavior in
the field is more predictable, we have combined a mini-Tn5 cloning system that
allows stable insertion of foreign genes into the chromosomes of a variety of
Gram-negative bacteria with a gene-containment circuit based on the universal
lethal-function colicin E3. Use of the system is exemplified by the construction
of a micro-organism designed to degrade polychlorinated biphenyls, important
environmental pollutants. The relevant genotype of the microorganism is subject
to a stringent gene-containment mechanism that provides neither an advantage nor
a disadvantage to the host cell for survival, but decreases frequencies of
productive chromosomal transfer frequencies by at least four orders of magnitude.
PMID- 9636323
TI - High level secretion of a humanized bispecific diabody from Escherichia coli.
AB - Clinical development of bispecific antibodies (BsAb) has been effectively stymied
by the lack of efficient production methods. We therefore attempted to produce a
humanized BsAb fragment using an expression system that has proved very
successful for secretion of monospecific Ab fragments from E. coli. An anti
p185HER2/anti-CD3 BsF(ab')2 was first recast into the diabody format and then
periplasmically secreted from E. coli grown to high cell density in a fermentor.
The diabody was recovered in very high yield (up to 935 mg/l) after protein A
purification and predominantly (> or = 80%) as a dimer as judged by size
exclusion chromatography. Diabody dimers were found to be mainly functional
heterodimers (approximately 75%) by titration with p185HER2 extracellular domain.
The diabody binds p185HER2 extracellular domain and human T lymphocytes with
affinities close to those of the parent BsF(ab')2. Furthermore, the diabody is
capable of simultaneous binding to tumor cells overexpressing p185HER2 and CD3 on
T cells as shown by cellular rosetting. The diabody is equally potent as the
parent BsF(ab')2 in retargeting IL-2 activated T-enriched peripheral blood
lymphocytes to lyse tumor cells overexpressing p185HER2.
PMID- 9636324
TI - Development of new cloning vectors for the production of immunogenic outer
membrane fusion proteins in Escherichia coli.
AB - The Pseudomonas aeruginosa lipoprotein gene (oprI) was modified by cloning an in
frame polylinker in both orientations at the end of oprI. The resulting plasmids
pVUB1 and pVUB2 allow high lipoprotein production in E. coli after IPTG
induction. The modified lipoproteins are present in the outer membrane and
surface-exposed. Outer membrane-bound fusion proteins of different sizes were
produced and used to generate antibodies without use of adjuvant. An 87 bp DNA
fragment from the vp72 capsid protein gene of African Swine Fever virus (ASFV)
and the entire Leishmania major glycoprotein gp63 gene were expressed in this
system. Finally, a fusion lipoprotein containing a 16 amino acid epitope from the
pre-S2b region of Hepatitis B virus (HBV) was presented by an antigen-presenting
cell line to a T-cell hybridoma while the corresponding cross-linked S2b peptide
was not. The results suggest that OprI-based fusion proteins can be used to
generate both humoral and cellular immune responses.
PMID- 9636325
TI - Thoughts on the prevention of neonatal group B streptococcal infection.
PMID- 9636326
TI - Drug-induced disorders.
PMID- 9636327
TI - Bacterial vaginosis: what's in a name?
PMID- 9636328
TI - Accidental coin swallowing and sublingual nitroglycerin.
PMID- 9636329
TI - Screening for prostate cancer.
PMID- 9636330
TI - Air bag deployment and hearing loss.
PMID- 9636331
TI - Novel treatment for leg ulcers.
PMID- 9636332
TI - Diagnostic evaluation of urinary incontinence in geriatric patients.
AB - In most cases, the evaluation of urinary incontinence requires only a history, a
physical examination, urinalysis and measurement of postvoid residual urine
volume. The initial purposes of the evaluation are to identify conditions
requiring referral or specialized work-up and to detect and treat reversible
causes that may be present. If the patient does not appear to require referral
and a reversible cause is not identified, the next step is to categorize the
patient's symptoms as typical of either urge or stress incontinence and treat the
patient accordingly. If treatment fails or a presumptive diagnosis of urge or
stress incontinence cannot be reached, the final step would be to perform more
sophisticated tests or refer the patient for testing to define the cause and
determine the best treatment.
PMID- 9636333
TI - Eyelid disorders: diagnosis and management.
AB - Eyelid problems range from benign, self-resolving processes to malignant,
possibly metastatic, tumors. Inflammation, infection, benign and malignant
tumors, and structural problems such as ectropion, entropion and blepharoptosis
may occur. Fortunately, most eyelid disorders are not vision-threatening or life
threatening; however, many cause irritative symptoms such as burning, foreign
body sensation or pain. Blepharitis, or eyelid inflammation, one of the most
common problems, is characterized by erythematous eyelids with accumulation of
debris along the eyelid margin. Malignant eyelid tumors may be associated with
lash loss and erosion of normal eyelid structures. Recognition and diagnosis of
these problems are crucial to their proper management. Warm compresses and
antibiotics suffice for many conditions, while excision, cryotherapy or laser
treatment are required for some.
PMID- 9636334
TI - The Charcot foot in diabetes: six key points.
AB - The Charcot foot commonly goes unrecognized, particularly in the acute phase,
until severe complications occur. Early recognition and diagnosis, immediate
immobilization and a lifelong program of preventive care can minimize the
morbidity associated with this potentially devastating complication of diabetic
neuropathy. If unrecognized or improperly managed, the Charcot foot can have
disastrous consequences, including amputation. The acute Charcot foot is usually
painless and may mimic cellulitis or deep venous thrombosis. Although the initial
radiograph may be normal, making diagnosis difficult, immediate detection and
immobilization of the foot are essential in the management of the Charcot foot. A
lifelong program of patient education, protective footwear and routine foot care
is required to prevent complications such as foot ulceration.
PMID- 9636335
TI - Prevention of neonatal group B streptococcal infection.
AB - Neonatal group B streptococcal infection is the primary cause of neonatal
morbidity related to infection. It can often be prevented by identifying and
treating pregnant women who carry group B streptococci or who are at highest risk
of transmitting the bacteria to newborns. Increasing evidence and expert opinion
support intrapartum treatment of women at relatively high risk of delivering an
infant with group B streptococcal infection. Such women can be identified through
the use of an anogenital culture for group B streptococci obtained at 35 to 37
weeks of gestation and by the presence of at least one of many risk factors
associated with neonatal infection. These risk factors include preterm labor or
rupture of the membranes at less than 37 weeks of gestation, previous delivery of
an infant with invasive group B streptococcal disease, group B streptococcal
bacteriuria during the present pregnancy, maternal intrapartum fever of 38
degrees C (100.4 degrees F) or higher and rupture of the fetal membranes for 18
hours or more. The recommended agent for intrapartum chemoprophylaxis is
intravenous penicillin G; clindamycin is used in penicillin-allergic women. The
use of risk markers alone to guide the administration of intrapartum antibiotics
is much more cost-effective than other preventive strategies, but it exposes more
women and infants to antibiotic-associated risks. Management of the infants of
treated mothers is empiric and is currently guided by expert opinion.
PMID- 9636336
TI - Current guidelines for antibiotic prophylaxis of surgical wounds.
AB - Appropriately administered antibiotic prophylaxis reduces the incidence of
surgical wound infection. Prophylaxis is uniformly recommended for all clean
contaminated, contaminated and dirty procedures. It is considered optional for
most clean procedures, although it may be indicated for certain patients and
clean procedures that fulfill specific risk criteria. Timing of antibiotic
administration is critical to efficacy. The first dose should always be given
before the procedure, preferably within 30 minutes before incision.
Readministration at one to two half-lives of the antibiotic is recommended for
the duration of the procedure. In general, postoperative administration is not
recommended. Antibiotic selection is influenced by the organism most commonly
causing wound infection in the specific procedure and by the relative costs of
available agents. In certain gastrointestinal procedures, oral and intravenous
administration of agents with activity against gram-negative and anaerobic
bacteria is warranted, as well as mechanical preparation of the bowel. Cefazolin
provides adequate coverage for most other types of procedures.
PMID- 9636337
TI - Assessment and treatment of bulimia nervosa.
AB - Bulimia nervosa is characterized by binge eating and inappropriate compensatory
behaviors, such as vomiting, fasting, excessive exercise and the misuse of
diuretics, laxatives or enemas. Although the etiology of this disorder is
unknown, genetic and neurochemical factors have been implicated. Bulimia nervosa
is 10 times more common in females than in males and affects up to 3 percent of
young women. The condition usually becomes symptomatic between the ages of 13 and
20 years, and it has a chronic, sometimes episodic course. The long-term outcome
has not been clarified. Other psychiatric conditions, including substance abuse,
are frequently associated with bulimia nervosa and may compromise its diagnosis
and treatment. Serious medical complications of bulimia nervosa are uncommon, but
patients may suffer from dental erosion, swollen salivary glands, oral and hand
trauma, gastrointestinal irritation and electrolyte imbalances (especially of
potassium, calcium, sodium and hydrogen chloride). Treatment strategies are based
on medication, psychotherapy or a combination of these modalities.
PMID- 9636338
TI - Treatment of systemic lupus erythematosus: an update.
AB - Systemic lupus erythematosus predominantly affects women and is more common in
blacks. Although survival rates have improved, over one half of patients with
systemic lupus erythematosus have permanent damage in one or more organ systems.
Arthritis and cutaneous manifestations are most common, but renal, hematologic
and neurologic manifestations contribute largely to morbidity and mortality.
Treatment approaches emphasize using a combination of drugs to minimize chronic
exposure to corticosteroids.
PMID- 9636339
TI - Sudden death in young athletes: screening for the needle in a haystack.
AB - Nontraumatic sudden death in young athletes is always disturbing, as apparently
invincible athletes, become, without warning, victims of silent heart disease.
Despite public perception to the contrary, sudden death in young athletes is
exceedingly rare. It most commonly occurs in male athletes, who have estimated
death rates nearly fivefold greater than the rates of female athletes. Congenital
cardiovascular disease is the leading cause of non-traumatic sudden athletic
death, with hypertrophic cardiomyopathy being the most common cause. Screening
athletes for disorders capable of provoking sudden death is a challenge because
of the low prevalence of disease, and the cost and limitations of available
screening tests. Current recommendations for cardiovascular screening call for a
careful history and physical examination performed by a knowledgeable health care
provider. Specialized testing is recommended only in cases that warrant further
evaluation.
PMID- 9636340
TI - Evaluating hoarseness: keeping your patient's voice healthy.
AB - Hoarseness is the term often used by patients to describe changes in their voice
quality. The causes of hoarseness are determined after obtaining a detailed
medical history of the circumstances preceding the onset of hoarseness and
performing a thorough physical examination. The latter may include visualization
of the vocal cords, possibly using indirect laryngoscopy, flexible
nasolaryngoscopy or strobovideolaryngoscopy. In the absence of an upper
respiratory tract infection, any patient with hoarseness persisting for more than
two weeks requires a complete evaluation. When the patient has a history of
tobacco use, cancer of the head and neck must be considered and ruled out. Voice
abuse is one of the most common causes of hoarseness and can lead to other vocal
pathologies such as vocal nodules. Good vocal hygiene can prevent and treat some
pathologies, and voice therapy is a cornerstone of management in some cases of
hoarseness.
PMID- 9636341
TI - Combination antiretroviral therapy for HIV infection.
AB - The primary goal of antiretroviral therapy for human immunodeficiency virus (HIV)
infection is suppression of viral replication. Evidence indicates that the
optimal way to achieve this goal is by initiating combination therapy with two or
more antiretroviral agents. The agents now licensed in the United States for use
in combination therapy include five nucleoside analog reverse transcriptase
inhibitors (zidovudine, didanosine, zalcitabine, stavudine and lamivudine), two
nonnucleoside reverse transcriptase inhibitors (delavirdine and nevirapine) and
four protease inhibitors (saquinavir, ritonavir, indinavir and nelfinavir).
Current recommendations suggest that antiretroviral therapy be considered in any
patient with a viral load higher than 5,000 to 20,000 copies per mL, regardless
of the CD4+ count. Selection of the combination regimen must take into account
the patient's prior history of antiretroviral use, the side effects of these
agents and drug-drug interactions that occur among these agents and with other
drugs as well. Because of the potential for viral resistance, nonnucleoside
reverse transcriptase inhibitors and protease inhibitors should only be used in
combination therapy. Antiretroviral agents are rapidly being developed and
approved, so physicians must make increasingly complex treatment decisions about
medications with which they may be unfamiliar.
PMID- 9636342
TI - Photo quiz. Flowering dermatosis.
PMID- 9636343
TI - Significant FDA approvals in 1997.
PMID- 9636344
TI - American Heart Association releases scientific statement on cardiovascular
disease in women.
PMID- 9636345
TI - AAP issues recommendations for the use of soy protein-based formulas in infant
feeding.
PMID- 9636346
TI - The value of measuring health care quality.
PMID- 9636347
TI - Sudden tachycardia in an octagenarian.
PMID- 9636348
TI - An inflamed elbow after an insect sting.
AB - A 63-year-old man presented with fever and a painfully swollen right elbow and
forearm. He had been stung by a yellow jacket two weeks earlier and had since
found it increasingly difficult to bend his arm.
PMID- 9636349
TI - Acute salicylate overdose.
PMID- 9636350
TI - Dosage in ulcer study.
PMID- 9636351
TI - Dizzy patients: the varieties of vertigo.
AB - Some vertigo results from acute viral labyrinthitis or a cerebrovascular event;
many cases are due to loose particulate matter within the semicircular canals. In
the vast majority of patients, a careful history and appropriate clinical tests
will suffice to identify the cause of the vertigo--and with benign paroxysmal
positional vertigo, a simple clinical maneuver can also provide a cure.
PMID- 9636352
TI - Evaluation and management of cervical polyps.
PMID- 9636353
TI - Rash and shortness of breath in an elderly woman.
PMID- 9636354
TI - Chronic hepatitis C: early intervention.
AB - Chronic hepatitis C infection is the most common liver disease in the United
States; it accounts for up to 12,000 deaths annually and is the most common
referral for liver transplantation. Recognition of acute infection is desirable
because treatment may prevent chronicity. Interferon remains the primary
treatment, but new agents and combinations are being developed.
PMID- 9636355
TI - Outpatient management of community-acquired pneumonia.
AB - Recently published guidelines permit the decision to treat patients with
community-acquired pneumonia on an outpatient basis to be made more confidently
than in the past. In most cases, the risk of 30-day mortality can be evaluated
without extensive laboratory testing. Antibiotic therapy with erythromycin or
doxycycline is generally effective.
PMID- 9636356
TI - Chronic myelogenous leukemia: extending the prospects for cure.
AB - Advances in our understanding of the molecular defects underlying this leukemia
have led to novel therapeutic approaches that have not only altered the natural
history of the disease but also apparently effected cures in some patients. The
next step may be to offer the possibility of a cure to all patients. Allogeneic
bone marrow and T cell transplantation shows promise in this regard.
PMID- 9636357
TI - Genetic stability of Sabin 1 strain of poliovirus: implications for quality
control of oral poliovirus vaccine.
AB - The Sabin vaccine strains of poliovirus, like all RNA viruses, exist as a
quasispecies of genomic sequences whose composition can be altered during virus
propagation. Since changes in vaccine virus during manufacture can enhance the
neurovirulent potential of the vaccine, each monovalent lot of oral poliovirus
vaccine (OPV) undergoes several tests to ensure consistency of manufacture,
including the monkey neurovirulence test (MNVT). Recently, we proposed a new
molecular approach for direct quantification of vaccine variants with
neurovirulent potential as an alternative way to monitor consistency of OPV
production. Analysis of the Sabin 1 genome allowed us to identify a limited
number of specific loci that exhibit significant change during viral propagation
in vitro and in vivo. Here we explore the possible roles of these changes and
show that 7427-U-->C and 7441-G-->A alterations in the 3'-UTR of the Sabin 1
virus do not increase monkey neurovirulence. These, as well as our previous
results, suggest that only mutations in the 5'-UTR play a significant role in the
limited increase in Sabin 1 monkey neurovirulence observed after extended
propagation of the virus beyond the passage level used in vaccine production. Our
studies with high-passage batches of the Sabin 1 strain confirmed the stability
of this strain, which retains acceptable levels of monkey neurovirulence even
after serial passages at elevated temperature. Compared to the MNVT, molecular
analysis of the genetic composition of Sabin 1 poliovirus provides a more
sensitive analytical approach to monitor consistency of vaccine production.
PMID- 9636358
TI - Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine
deaminase.
AB - The virus-associated VAI RNA of adenovirus is a small highly structured RNA that
is required for the efficient translation of cellular and viral mRNAs at late
times after infection. VAI RNA antagonizes the activation of the interferon
inducible RNA-dependent protein kinase, PKR, an important regulator of
translation. The RNA-specific adenosine deaminase, ADAR, is an interferon
inducible RNA-editing enzyme that catalyzes the site-selective C-6 deamination of
adenosine to inosine. ADAR possesses three copies of the highly conserved RNA
binding motif (dsRBM) that are similar to the two copies found in PKR, the enzyme
in which the prototype dsRBM motif was discovered. We have examined the effect of
VAI RNA on ADAR function. VAI RNA impairs the activity of ADAR deaminase. This
inhibition can be observed in extracts prepared from interferon-treated human
cells and from monkey COS cells in which wild-type recombinant ADAR was
expressed. Analysis of wild-type and mutant forms of VA RNA suggests that the
central domain is important in the antagonism of ADAR activity. These results
suggest that VAI RNA may modulate viral and cellular gene expression by
modulating RNA editing as well as mRNA translation.
PMID- 9636359
TI - Cyclophilin a modulates processing of human immunodeficiency virus type 1 p55Gag:
mechanism for antiviral effects of cyclosporin A.
AB - The molecular chaperone cyclophilin A (Cyp A) modulates human immunodeficiency
virus type 1 (HIV-1) infectivity through its interactions with Gag structural
proteins. The molecular mechanism for CypA in HIV-1 replication is not known. We
studied chaperone effects on Gag precursor processing using cyclosporin A (CsA)
to bind CypA and prevent its interaction with p55Gag. CsA treatment inhibited
p55Gag processing in extracellular virus-like particles produced from COS cells.
We confirmed the effect of CsA on Gag processing by examining virions produced
from CEMx174 cells infected with HIV-1LAI. Particles accumulated in the presence
of CsA displayed mostly immature virion morphology and lacked condensed capsids.
CsA has a direct effect on HIV-1 Gag processing that implicates CypA as having an
important role in the maturation of HIV-1 particles.
PMID- 9636360
TI - Subcellular localization and some biochemical properties of the flavivirus Kunjin
nonstructural proteins NS2A and NS4A.
AB - In a previous study on the replication of Kunjin virus using immunoelectron
microscopy (E. G. Westaway, J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A.
Khromykh, 1997, J. Virol. 71, 6650-6661), NS1 and NS3 were found associated with
double-stranded RNA (dsRNA) within vesicle packets (VP) in infected Vero cells,
suggesting that these induced membrane structures may be the cytoplasmic sites of
RNA replication. NS2B and NS3 (comprising the virus-encoded protease) were
colocalized within distinct paracrystalline (PC) or convoluted membranes (CM),
also induced in the cytoplasm, suggesting that these membranes are the sites of
proteolytic cleavage. In this study we found by immunofluorescence (IF) that the
small hydrophobic nonstructural proteins NS2A and NS4A were located in discrete
foci in the cytoplasm of infected cells at both 16 and 24 h postinfection,
partially coincident with dsRNA foci. In cryosections of infected cells at 24 h,
NS2A was located by immunogold labeling primarily within VP, associated with
labeled dsRNA. NS2A fused to glutathione S-transferase (GST) bound strongly to
the 3' untranslated region of Kunjin RNA and also to the proposed replicase
components NS3 and NS5 in cell lysates. NS4A was localized by immunogold labeling
within a majority of the virus-induced membranes, including VP, CM, and PC. GST
NS4A bound weakly to the 3' untranslated region of Kunjin RNA but was bound to
NS4A strongly and to most of the other viral nonstructural proteins, including
NS3 and NS5. Taken together the results indicate that the flavivirus replication
complex includes NS2A and NS4A in the VP in addition to the previously identified
NS1 and NS3.
PMID- 9636361
TI - Mouse adenovirus type-1 replication is restricted to vascular endothelium in the
CNS of susceptible strains of mice.
AB - Previous studies have shown that mouse adenovirus type-1 (MAV-1) caused a fatal
hemorrhagic encephalitis in certain strains of mice. C57BI/6 mice exhibited 100%
mortality when given as little 10(3) plaque-forming units (PFU) of MAV, in
contrast to BALB/c mice which were resistant to as many as 10(6) PFU. Susceptible
animals died with a flaccid paralysis on the 3rd or 4th day after inoculation.
The brains and spinal cords of these animals displayed numerous petechial
hemorrhages that were found in virtually all areas of the brain, but were more
numerous in white matter. In this paper, immunohistochemistry and electron
microscopy were used to identify the viral target of replication within the CNS
of susceptible mice. These studies showed that the CNS vascular endothelial cell
was the primary site of viral replication within the CNS of mice infected with
MAV-1. Characterization of cytokine mRNA levels and disease course in
immunodeficient mice revealed that the host immune response played little, if
any, role in the pathogenesis of MAV-1 disease in susceptible mice and was not
responsible for the resistance of BALB/c mice. These results support the
conclusion that disease course and outcome in susceptible and resistant strains
of mice were determined primarily by the ability of the virus to replicate within
the CNS vascular endothelium.
PMID- 9636362
TI - The predominant elF4G-specific cleavage activity in poliovirus-infected HeLa
cells is distinct from 2A protease.
AB - Human enteroviruses and rhinoviruses rapidly and selectively abolish translation
from cellular mRNA upon infection of susceptible cells. Expression of the
poliovirus 2A protease (PV 2Apro) is sufficient to cause host translation shutoff
through cleavage of elF4G (formerly p220, elF4 gamma) either directly or
indirectly through activation of a cellular factor. Evidence exists for both
direct and indirect cleavage mechanisms; however, factors presumed to participate
in an indirect mechanism have not yet been purified or defined. Here we show that
the dominant elF4G cleavage activity in lysates from infected HeLa cells was
separable from PV 2Apro by size exclusion chromatography. 2Apro separated into
two peak fractions which contained activity which cleaved a peptide substrate
derived from the poliovirus polyprotein. These peak 2Apro fractions did not
cleave elF4G or an elF4G-derived peptide, as expected, due to the poor efficiency
of direct cleavage reactions. Conversely, fractions which contained peak elF4G
cleavage activity and only trace amounts of 2Apro efficiently cleaved a peptide
substrate derived from the previously mapped elF4G cleavage site and also cleaved
a peptide derived from the poliovirus 1D2A region. The dominant elF4G cleavage
activity was highly purified through four chromatography steps and found to be
devoid of all traces of 2Apro or its precursors. Quantitation of 2Apro from
lysates of infected cells showed that during infections in HeLa cells, 2Apro does
not reach molar excess over elF4G, as previously shown to be required for direct
elF4G cleavage in vitro. Further, infection of HeLa cells in the presence of 2 mM
guanidine-HCl, a potent inhibitor of viral RNA replication, suppressed
accumulation of 2Apro and its precursor 2ABC below detectable levels but was
unable to delay the onset of elF4G proteolysis in vivo. The elF4G cleavage
activity was still easily detectable in in vitro assays using fractions from
guanidine-treated cells. Thus, the data suggest that poliovirus utilizes two
catalytic activities to ensure rapid cleavage of elF4G in vivo. Although it was
not directly measurable here, 2Apro likely does cleave a portion of elF4G in
cells. However, the data suggest that a cellular factor which can be activated by
small quantities of 2Apro constitutes the bulk of the elF4G-specific cleavage
activity in infected cells and is responsible for the rapid and efficient elF4G
cleavage activity observed in vivo.
PMID- 9636363
TI - Direct cleavage of elF4G by poliovirus 2A protease is inefficient in vitro.
AB - Previously, the purified recombinant 2A proteases (2Apro) of coxsackievirus B4
(CVB4) and human rhinovirus type 2 (HRV2) were shown to cleave synthetic peptides
derived from human or rabbit elF4G as well as elF4G protein purified from rabbit
reticulocytes. These results were in contrast to previous evidence which
supported the view that elF4G cleavage activity in poliovirus-infected HeLa cells
required a cellular factor(s) activated by poliovirus (PV) 2Apro. In the present
study, recombinant PV 2Apro was shown to cleave either rabbit or human elF4G or
their derived peptides in direct cleavage reactions, but cleaved the 4G-derived
peptides with 100-fold lower efficiency than with a peptide derived from the
poliovirus polyprotein. In these experiments, up to 25-fold molar excess of 2Apro
over elF4G protein was required to cause greater than 50% cleavage. CVB4 2Apro
was also tested in peptide cleavage assays under the same conditions as PV 2Apro
and was found to cleave all elF4G substrates with efficiencies similar to PV
2Apro. Finally, cleavage reactions utilizing recombinant elF4G containing a G486E
substitution at the cleavage site for CVB4 and HRV2 proteases resulted in
drastically reduced cleavage by PV 2Apro, similar to the reduction previously
seen with HRV2 and CVB4 2Apro, confirming that all three viral 2A proteases
recognize the same cleavage site on elF4G. These data show that PV 2Apro can
directly cleave elF4G in vitro with efficiencies similar to those of CVB 2Apro,
but cleavage efficiency of elF4G is approximately 1000-fold lower than cleavage
of a peptide derived from the authentic 2A cleavage site on the poliovirus
polyprotein.
PMID- 9636364
TI - Three active forms of aspartic proteinase from Mason-Pfizer monkey virus.
AB - Mason-Pfizer monkey virus (M-PMV) proteinase, released by the autocatalytic
cleavage of Gag-Pro and Gag-Pro-Pol polypeptide precursors, catalyzes the
processing of viral precursors to yield the structural proteins and enzymes of
the virion. In retroviruses, usually only one proteolytically active form of
proteinase exists. Here, we describe an unusual feature of M-PMV, the existence
of three active forms of a retroviral proteinase with molecular masses of 17, 13,
and 12 kDa as determined by mass spectroscopy. These forms arise in vitro by self
processing of a 26-kDa proteinase precursor. We have developed a process for
isolation of each truncated product and demonstrate that all three forms display
proteolytic activity. Amino acid analyses, as well as the determination of N- and
C-terminal sequences, revealed that the N-termini of all three forms are
identical, confirming that in vitro autoprocessing of the 17-kDa form occurs at
the C-terminus to yield the truncated forms. The 17-kDa form and the newly
described 13-kDa form of proteinase were identified in virions collected from the
rhesus monkey CMMT cell line chronically infected with M-PMV, confirming that
multiple forms exist in vivo.
PMID- 9636365
TI - The cAMP-dependent protein kinase A and protein kinase C-beta pathways
synergistically interact to activate HIV-1 transcription in latently infected
cells of monocyte/macrophage lineage.
AB - The HIV-1 long terminal repeat (LTR) responds to a variety of cellular signal
transduction pathways. We demonstrate that the cAMP-dependent protein kinase A
(PKA) and protein kinase C (PKC) signaling pathways synergize to increase HIV-1
LTR-mediated transcription and viral replication in a latently infected
promonocytic cell line (U1). The LTR-mediated synergy induced by cholera toxin
(Ctx), a potent activator of the cAMP-dependent PKA pathway, and the PKC
activator phorbol 12-myristate 13-acetate (PMA) was abrogated by a PKC-beta
specific inhibitor (LY333531). In contrast, the LTR-mediated synergy induced by
Ctx and TNF alpha was not affected by LY333531. The synergy induced by Ctx and
TNF alpha was also abrogated by mutation of the cAMP-responsive downstream
sequence elements (DSE) in the 5' untranslated leader region, whereas the DSE
mutations did not affect the synergy induced by Ctx and PMA. These distinctions
indicate that Ctx cooperates differently with TNF alpha and PMA to activate the
HIV-1 LTR. Ctx and PMA synergistically activated AP-1- and NF-kappa B-dependent
transcription, even though no cooperative binding of AP-1 or NF-kappa B was
observed in gel shift assays. An extensive mutational analysis of the HIV-1 LTR
that included the NF-kappa B and AP-1 binding sites revealed no distinct cis
acting element or region within the HIV-1 LTR that was required for the
transcriptional synergy. Ctx and PMA also synergistically interact to activate
the HTLV-1 LTR. These results indicate that the transcriptional synergy elicited
by Ctx and PMA targets multiple functional elements and promoters, requires a
cooperative interaction between the PKA and PKC-beta pathways, and differs
mechanistically from the transcriptional synergy induced by Ctx and TNF alpha.
PMID- 9636366
TI - The role of IL-10 in mouse hepatitis virus-induced demyelinating
encephalomyelitis.
AB - Interleukin 10 (IL-10) is an important anti-inflammatory cytokine. To examine its
role in virus-induced encephalomyelitis, IL-10-deficient (IL-10 -/-) mice were
infected with a neurotropic strain of mouse hepatitis virus (JHMV). JHMV-infected
IL-10 -/- mice, compared to IL-4 -/- and syngeneic C57BL/6 mice, exhibited
increased morbidity and mortality. Virus was cleared from the CNS of all groups
of mice with equal kinetics by day 9 postinfection and the lack of either IL-4 or
IL-10 did not alter the distribution of viral antigen, suggesting a lack of
correlation between viral replication and the increased clinical disease in IL-10
-/- mice. In moribund IL-10 -/- mice, a moderate increase in mononuclear cell
infiltration was correlated with increased expression of tumor necrosis factor
alpha, interferon-gamma, and inducible nitric oxide synthase mRNAs. In the small
percentage of IL-10 -/- mice that survived, no differences in either
demyelination or inflammation were observed. Together, these results suggest that
IL-10 is not required for viral clearance, and although it appears to be one of
the mechanisms responsible for inhibiting the extent of inflammation in the CNS
during acute JHMV infection, it has little role in the eventual resolution of CNS
inflammatory responses.
PMID- 9636367
TI - Characterization of a linear epitope in the nonstructural region 4 of hepatitis C
virus with reactivity to seroconversion antibodies.
AB - Mapping and possible diagnostic meaning of a highly conserved, linear NS4 epitope
(NS4/3), located outside the C100-3 antigen within the carboxyl terminal
proportion of the NS4 region, with major immunoreactivity with specimens of
patients with HCV infection from various geographic origins is described.
Transient, acute-phase IgM anti-HCV NS4/3 was detected coincidentally or earlier
than active IgG anti-HCV NS4/3 response with four well-characterized
seroconversion panels. GenBank alignment studies identified patch homologies
between the NS4/3 sequence and a number of non-HCV proteins, which may explain
part of the cross-reactivity of the NS4/3 epitope. Some of the "false positive
reactivities" of the NS4/3 epitope with asymptomatic blood donors, not being
confirmed with FDA-approved anti-HCV assays without the NS4/3 epitope, may be
explained by recognition of very early seroconversion antibodies.
PMID- 9636368
TI - DNA sequences outside the simian virus 40 early region cause downregulation of T
antigen production in permissive simian cells.
AB - Using a series of modified wtSV40 and early region SV40 DNAs we assayed the
effect of viral late region sequences on T-antigen production by the SV40 early
region. We found that SV40 late region (L-SV40) DNA sequences reduced T-antigen
(T-Ag) production by the SV40 early region (E-SV40) when both viral regions were
linked as they are in wtSV40 DNA. This was demonstrated by Western analysis which
showed that E-SV40 DNA produced 10 times more T-Ag than wtSV40 DNA L-SV40, with
its own promoter but unlinked to E-SV40 DNA, also greatly inhibited T-Ag
production when it was contrasfected with E-SV40. Therefore, L-SV40 DNA inhibited
T-Ag production by E-SV40 DNA when present in cis or in trans. We have shown that
expression of the SV40 late transcription unit dominated that of the early (T-Ag
gene) transcription unit because late region RNA accumulated to much higher
levels than early viral RNA. However, in contrasfected cells L-SV40 DNA did not
replicate to higher levels than E-SV40 DNA. We offer a model for control of T-Ag
expression in which a relatively small amount of T-Ag activates late
transcription at the expense of T-Ag gene transcription and that this represents
a switch from early to late viral gene expression. We suggest that when
activation of the late transcription unit occurs at the late promoter, expression
of the T-Ag gene is greatly reduced. The L-SV40 promoter may inhibit T-Ag gene
transcription by sequestering cellular factors required for early transcription,
factors which may be present in limited amounts. We suggest further that
activation of late transcription allows for the necessary production of large
amounts of capsomeres and virions and downregulation of early transcription
prevents the early region from interfering with capsid synthesis. We tested the
model using a construct with a wild-type T-Ag gene but with mutations in the SV40
major late promoter which prevent the promoter from being bound by cellular
repressors of late transcription. We found that this construct, which
overproduces late SV40 RNA, was defective for T-Ag production. This indicates
that activation of the late promoter results in repression of T-Ag gene
expression.
PMID- 9636369
TI - Characterization of the two overlapping papain-like proteinase domains encoded in
gene 1 of the coronavirus infectious bronchitis virus and determination of the C
terminal cleavage site of an 87-kDa protein.
AB - In a previous report, we showed that proteolytic processing of an 87-kDa mature
viral protein from the coronavirus infectious bronchitis virus (IBV) 1a and 1a/1b
polyproteins was mediated by two putative overlapping papain-like proteinase
domains (PLPDs) encoded within the region from nucleotides 4243 to 5553 of ORF 1a
(Liu et al., 1995). In this study, we demonstrate that only the first domain,
PLPD-1, is responsible for this cleavage, as deletion of the second domain did
not affect the formation of the 87-kDa protein. Site-directed mutagenesis studies
further showed that a previously predicted nucleophilic cysteine residue
(Cys1274) and a histidine residue (His1437) were essential for the proteinase
activity, indicating that they may be important components of the catalytic
center of the proteinase. Meanwhile, expression of a series of deletion mutants
revealed that the 87-kDa protein was encoded by the 5'-most 2.6 kb of ORF 1a.
Deletion and amino acid substitution mutation studies demonstrated that the
Gly673-Gly674 dipeptide bond was most likely the cleavage site responsible for
releasing the C-terminus of the 87-kDa protein from the 1a and 1a/1b
polyproteins.
PMID- 9636370
TI - Characterization of the interactions among vaccinia virus transcription factors
G2R, A18R, and H5R.
AB - Prior genetic analysis suggests that there may exist an interaction between the
products of the vaccinia virus genes A18R, a putative negative transcription
elongation factor, and G2R, a putative positive transcription elongation factor.
In addition, affinity purification of polyhistidine-tagged G2R protein
overexpressed in vaccinia virus-infected cells, reported here, results in
copurification of the vaccinia H5R protein, previously characterized as a late
viral transcription factor. We have therefore used several methods to screen
further for interactions among the G2R, A18R, and H5R proteins. Methods include
copurification or co-immunoprecipitation of proteins overexpressed during
vaccinia virus infection, activation of the gal 4 promoter by gal 4 fusions in
the yeast two-hybrid system, and co-immunoprecipitation of proteins synthesized
in vitro in a rabbit reticulocyte lysate. The results reveal interactions which
include all possible pairwise combinations of the three proteins G2R, A18R, and
H5R; however, not all possible permutations of the interactions are observed and
the interactions are not observed in all environments tested. The results suggest
that the vaccinia virus proteins G2R, A18R, and H5R interact as part of a higher
order transcription complex.
PMID- 9636371
TI - HHR23A, the human homologue of the yeast repair protein RAD23, interacts
specifically with Vpr protein and prevents cell cycle arrest but not the
transcriptional effects of Vpr.
AB - Yeast two-hybrid selection of proteins interacting with human immunodeficiency
virus type 1 Vpr identified HHR23A, a human homologue of the yeast DNA repair
protein RAD23, as a specific interactor. A small 57-amino-acid C-terminal portion
of HHR23A was sufficient for Vpr interaction. When introduced into human cells by
transfection, full-length HHR23A or its C-terminal fragments were able to
alleviate Vpr-induced cell cycle arrest, suggesting that HHR23A may participate
in the pathway leading to G2 arrest by Vpr. We have also examined the effects of
HHR23 on the recently identified transcription coactivator function of Vpr. The
two Vpr functions are independent, since we have identified mutants lacking
either the cell cycle arrest or the coactivator function. Our analysis showed
that excess of HHR23A does not affect the coactivator function of Vpr, while it
affects the cell cycle arresting function. Therefore, a simple sequestering model
for Vpr in the presence of excess HHR23A is not supported. We propose that the
interaction of HHR23A with Vpr may affect specifically pathways leading to cell
cycle regulation.
PMID- 9636372
TI - High-temperature inducible cell-free transcription and replication of double
stranded RNAs within the parasitic protozoan Cryptosporidium parvum.
AB - Sporozoites of the protozoan parasite, Cryptosporidium parvum, were found to
contain free, full-size plus strands transcribed from two extrachromosomal,
cytoplasmic, virus-like double-stranded RNAs (dsRNAs). Cell-free transcription
and replication of both dsRNAs were observed in crude sporozoite lysates. RNA
polymerase activity was found to be dependent upon addition of Mg2+ or Mn2+, as
well as the four ribonucleoside triphosphates, and was insensitive to inhibitors
of cellular DNA-dependent RNA polymerase. Semiconservative transcription of the
dsRNAs (plus strand synthesis) was observed at a wide range of temperatures, with
an optimum of 50 degrees C. In contrast, replication (minus strand synthesis) was
detected only at 50 and 60 degrees C.
PMID- 9636373
TI - Differential association of uracil DNA glycosylase with SIVSM Vpr and Vpx
proteins.
AB - The HIV-1 Vpr protein is a virion-associated protein which has been shown to
facilitate infection of nondividing macrophages and additionally to alter cell
cycle and proliferation status of the infected host cell. HIV-1 Vpr also was
recently shown to associate with the DNA repair enzyme uracil DNA glycosylase
(UDG). This association with a DNA repair enzyme is intriguing given that
nonprimate lentiviruses encode a dUTPase, which, like UDG, minimizes the
misincorporation of uracil into DNA and is important for virus replication in
primary nondividing macrophages but not in dividing cells. This raises the
possibility that the dependence upon Vpr for infection of nondividing macrophages
may relate to its ability to interact with UDG. Members of the HIV-2/SIVSM group
encode, in addition to Vpr, a related protein called Vpx. We previously
demonstrated (Fletcher et al., 1996) that Vpx of HIV-2/SIVSM is necessary and
sufficient for infection of primary macaque macrophages, while Vpr is not
required for macrophage infection but governs cell cycle arrest. Here, we extend
on these observations by demonstrating that Vpr, but not Vpx of HIV-2/SIVSM,
associates with UDG, which suggests that Vpx facilitates infection of macrophages
by a UDG-independent mechanism.
PMID- 9636374
TI - Identification of two replicons in phage-plasmid P4.
AB - DNA replication of phage-plasmid P4 proceeds bidirectionally from the ori1 site
(previously named ori), but requires a second cis-acting region, crr. Replication
depends on the product of the P4 alpha gene, a protein with primase and helicase
activity, that binds both ori1 and crr. A negative regulator of P4 DNA
replication, the Cnr protein, is required for copy number control of plasmid P4.
Using a plasmid complementation test for replication, we found that two
replicons, both dependent on the alpha gene product, coexist in P4. The first
replicon is made by the cnr and alpha genes and the ori1 and crr sites. The
second is limited to the alpha and crr region. Thus, in the absence of the ori1
region, replication can initiate at a different site. By deletion mapping, a cis
acting region, ori2, essential for replication of the alpha-crr replicon was
mapped within a 270-bp fragment in the first half of the alpha gene. The ori2
site was found to be dispensable in a replicon that contains ori1. A construct
that besides crr and alpha carries also the cnr gene was unable to replicate,
suggesting that Cnr not only controls replication from ori1, but also silences
ori2.
PMID- 9636375
TI - A surface immunodeterminant of human papillomavirus type 16 minor capsid protein
L2.
AB - We used human papillomavirus type 16 (HPV-16) particles composed of capsid
proteins L1 and L2 (L1/L2 capsids) as an antigen to produce mouse monoclonal
antibodies (MAbs). Of 18 MAbs recognizing surface epitopes of L1/L2 capsids, 1
was an anti-L1 MAb and 17 were anti-L2 MAbs. Seven of 11 anti-L2 MAbs recognizing
linear epitopes wer found to bind to a synthetic peptide with an HPV-16 L2
sequence of amino acids (aa) 69-81, which is within a highly conserved region
among different HPVs. The synthetic peptide reacted with the human sera that had
been shown to be positive for an antibody against HPV-16, -18, -58, or -6b
capsids composed of L1 alone. The data suggest that the HPV-16 L2 region of aa 69
81 contains a type-common immunodeterminant exposed on the surface of HPV
virions.
PMID- 9636376
TI - Vaccinia virus nucleoside triphosphate phosphohydrolase I is an essential viral
early gene transcription termination factor.
AB - Deng and Shuman (J. Biol Chem. 271, 29386 (1996)) reported that an ATPase
different from the known viral termination factor, VTF, is required for vaccinia
virus early gene transcription termination. Properties of this ATPase were
similar to those of a known vaccinia virus enzyme, nucleoside triphosphate
phosphohydrolase I (NPH I) the product of gene D11L. Transcription-competent cell
free extracts were prepared from A549 cells infected with wild-type or mutant
vaccinia virus harboring ts mutations in gene D11L. These extracts were employed
to investigate the role of NPH I in early gene transcription termination.
Extracts prepared under nonpermissive conditions from both wild-type virus and ts
mutant virus-infected cells exhibited high levels of early and intermediate gene
transcription activity but were incapable of supporting late gene transcription.
ts mutant extract lacked signal-dependent early gene transcription termination
activity, which was restored by the addition of either free NPH I or a GST-NPH I
fusion protein. A comparison of the NPH I amino acid sequence to the protein
databases revealed the presence of a set of sequences characteristic of nucleic
acid helicase superfamily II members. A series of site-specific mutations in the
helicase motifs and N-terminal and C-terminal deletion mutations were expressed
as GST fusion proteins and their activities assessed. Of the mutations in
helicase motifs I to VI, alteration of all but motif III reduced the ATPase
activity. Removal of as few as 24 amino acids from the N-terminal end eliminated
ATPase activity, while deletion of 68 C-terminal amino acids exhibited only a
modest decrease in ATP hydrolysis. Larger C-terminal deletions eliminated ATPase
activity. Each deletion mutation, and site-specific mutations other than the
motif III mutation, failed to support transcription termination in vitro.
Mutations in motifs I, II, V, and VI inhibit wild-type NPH I transcription
termination activity. However, deletion of up to 68 amino acids from the C
terminal end eliminates this inhibitory property. This observation is
particularly interesting since these C-terminal deletions retain both ATPase
activity and single-stranded DNA binding activity. Their failure to inhibit
transcription termination suggests that these C-terminal deletion mutations
eliminate a site required for a function other than from DNA binding or ATP
hydrolysis.
PMID- 9636378
TI - Combined blockade of CD28/B7 and CD40/CD40L costimulatory pathways prevents the
onset of chronic rejection.
PMID- 9636377
TI - Blockade of alpha 4 beta 1-integrin-fibronectin adhesive interactions prevents
chronic allograft rejection in sensitized recipients.
PMID- 9636379
TI - Prolonged survival of recipient rats with Fas-ligand-transfected liver allografts
by using HVJ-liposome.
PMID- 9636380
TI - TGF-beta: a link between immunosuppression, nephrotoxicity, and CsA.
PMID- 9636381
TI - Accelerated arteriosclerosis in aortic grafts: a role for cytokines in
progressive intimal lesion development.
PMID- 9636382
TI - Effect of cyclosporine and Sirolimus on interleukin-15-driven proliferation of
OKT3-preactivated human lymphocytes.
PMID- 9636383
TI - Long-term treatment with CsA decreases INF-gamma mRNA and increases pre-pro-ET-1
mRNA in rat kidneys.
PMID- 9636384
TI - Is TGF-beta a profibrotic cytokine in human renal transplants?
PMID- 9636385
TI - High local production of nitric oxide as a possible mechanism by which rapamycin
prevents transplant arteriosclerosis.
PMID- 9636386
TI - Activation of COL3A1 promoter activity by cyclosporine.
PMID- 9636387
TI - Expression of collagen by renal fibroblasts treated with FK 506 in vitro.
PMID- 9636388
TI - Differences in the mode of action of cyclosporine and FK 506.
PMID- 9636389
TI - Effect of mycophenolate mofetil on atherosclerosis in a rabbit model: initial
histologic and immunohistochemical analyses.
PMID- 9636390
TI - Hyperacute skin allograft rejection in presensitized rats is abrogated by
malononitrilamides.
PMID- 9636391
TI - Inhibition of alloreactivity in the popliteal lymph node assay by
malononitrilamides.
PMID- 9636392
TI - In vitro efficacy of conjugates of anti-CD45 monoclonal antibodies with plant
toxin A-chains.
PMID- 9636393
TI - Effect of the lazaroid U-74389G on chemokine gene expression and apoptosis in
renal ischemia-reperfusion injury.
PMID- 9636394
TI - Malononitrilamides reduce IgM and IgG xenoantibodies and prolong skin xenograft
survival in a mouse-to rat model.
PMID- 9636395
TI - Immunosuppressive effect of the hydrophobic extract of a Chinese herb on rat lung
allograft rejection.
PMID- 9636396
TI - Effect of mycophenolate mofetil on the in vivo infiltration of lymphocytes in the
rat remnant kidney.
PMID- 9636397
TI - In vitro study of BCX-34: a new human T-lymphocyte-specific purine phosphorylase
inhibitor.
PMID- 9636398
TI - Comparison of the effect of FK 506 and alpha/beta-T-cell antibody R73 on
transplant vascular sclerosis after heterotopic rat heart transplantation.
PMID- 9636399
TI - Different effects of cyclosporine or tacrolimus on hepatocyte acute phase
proteins.
PMID- 9636400
TI - An investigation into the effects of cyclosporine and FK 506 on the progress of
chronic rejection in the rat aortic model.
PMID- 9636401
TI - HMG-CoA reductase inhibitors pravastatin and simvastatin inhibit human B
lymphocyte activation.
PMID- 9636402
TI - Oral delivery of low molecular weight heparin in rat cardiac allografts.
PMID- 9636403
TI - Pravastatin and cyclosporine inhibit platelet-derived growth factor-stimulated
vascular smooth muscle cell mitogenesis: an investigation of mechanisms.
PMID- 9636404
TI - Liposomal tacrolimus: drug migration within blood compartments.
PMID- 9636405
TI - T cells infiltrating coronary arteries of cardiac allografts with chronic
rejection contain clonally expanded T lymphocytes.
PMID- 9636406
TI - Early treatment of acute rejection prevents chronic rejection in a rat model of
allogenic left lung transplantation.
PMID- 9636407
TI - Downregulation of endothelin expression in allograft coronary arteries after gene
therapy targeting Cdk2 kinase.
PMID- 9636408
TI - Effect of low molecular weight heparin on suppression of chronic graft vascular
disease in a rat cardiac allograft model.
PMID- 9636409
TI - Effect of cyclosporine on chronic graft vascular disease in a rat cardiac
isograft model.
PMID- 9636410
TI - Effect of hemodynamics on graft rejection in the heterotopic heart
transplantation model.
PMID- 9636411
TI - Accelerated arteriosclerosis in aortic grafts: a role for activated complement
and IgM antibody in early lesion development.
PMID- 9636412
TI - An experimental model of ischemia-produced transplant arteriosclerosis.
PMID- 9636413
TI - Cellular surface molecular and cytokine gene expression in rat heart allografts
under optimal doses of cyclosporine and FK 506.
PMID- 9636414
TI - Influence of initial antigen-independent events on acute allograft rejection:
inhibition by a soluble P-selectin ligand and low-dose cyclosporine in
combination.
PMID- 9636415
TI - Development of a macromolecular prodrug of FK 506: III: In vivo disposition of FK
506-dextran conjugate.
PMID- 9636416
TI - Development of a macromolecular prodrug of FK 506: II: In vitro study for FK 506
dextran conjugate.
PMID- 9636417
TI - Combined effect of rapamycin and cyclosporine in the prevention of rat corneal
allograft rejection.
PMID- 9636418
TI - Rapamycin's effect on vasomotion in the rat.
PMID- 9636419
TI - FK 506 and rapamycin in combination are not antagonistic but produce extended
small bowel graft survival in the mouse.
PMID- 9636420
TI - Donor-specific blood transfusion does not enhance the effect of FTY720 in rat
cardiac allotransplantation.
PMID- 9636421
TI - Prevention of experimentally induced autoimmune type I diabetes in rats by the
new immunosuppressive reagent FTY720.
PMID- 9636422
TI - An effect of FTY720 on acute rejection in canine renal transplantation.
PMID- 9636423
TI - Comparative effects of malononitriloamide analogs of leflunomide on whole blood
lymphocyte stimulation in humans, rhesus macaques, cats, dogs, and rats.
PMID- 9636424
TI - Mycophenolate mofetil's effect on accelerated heart allograft rejection and
rejection markers in the rat.
PMID- 9636425
TI - Methylprednisolone in bilayer liposomes prolongs cardiac and renal allograft
survival, inhibits macrophage activation, and selectively modifies antigen
presentation and T-helper cell function in rat recipients.
PMID- 9636426
TI - Tumor recurrence in liver grafts: two animal models.
PMID- 9636427
TI - CD95L confers immune priviledge to liver grafts which are spontaneously accepted.
PMID- 9636428
TI - Anti-human class I alpha 3 domain-specific monoclonal antibody induces programmed
cell death in murine cells expressing human class I MHC transgenes.
PMID- 9636429
TI - Blocking of costimulatory pathways using monoclonal antibodies as a new strategy
to prevent transplant rejection in a non-human primate model.
PMID- 9636431
TI - Intrathymic inoculation of donor bone marrow at the time of transplantation plus
a short course of tacrolimus induce long-term acceptance to rat lung allografts.
PMID- 9636430
TI - CD4-targeted therapy and CD28-B7 costimulatory blockage may independently induce
tolerance in sensitized allograft recipients.
PMID- 9636432
TI - Beneficial immunosuppressive effect of FTY720 combined with intrathymic injection
of splenic cells on rat pancreaticoduodenal allograft.
PMID- 9636433
TI - Inhibition of intestinal allograft rejection by an anti-CD8 monoclonal antibody
is not mediated by depletion alone.
PMID- 9636434
TI - Prevention of recurrence of autoimmune diabetes type I in rats following
pancreaticoduodenal transplantation.
PMID- 9636435
TI - Differential resistance of the cellular immune responses and immunoregulatory
properties of human cadaveric donor bone marrow cells to immunosuppressive drugs
commonly used in transplantation.
PMID- 9636436
TI - Development of tolerance in a chronic rejection model.
PMID- 9636437
TI - Prolonged rat cardiac allograft survival using adenoviral vector containing the
CTLA4Ig gene.
PMID- 9636438
TI - Construction of a single-chain antibody derived from 5H7, a monoclonal antibody
specific for a death signaling domain of human class I major histocompatibility
complex.
PMID- 9636440
TI - Effects of immunosuppression and pretransplant splenectomy in newborn cardiac
xenograft survival.
PMID- 9636439
TI - Squirrel monkeys hyperacutely reject porcine musculocutaneous flaps despite a
lack of naturally occurring xenoantibodies.
PMID- 9636441
TI - Analysis of B cell subsets responsible for the production of anti-donor
antibodies in hamster-to-rat xenorejection.
PMID- 9636442
TI - A novel in vitro model for xenorejection and immune mechanisms using
bioengineered living skin equivalents.
AB - We hypothesized that an in vitro bioengineered skin (LSE) could be used for the
study of xenogeneic inflammatory or immunosuppressive mechanisms. Murine
fibroblasts (10(4)/mL) were mixed with type 1 rat-tail collagen to form a matrix
(approximately 5 days) on which human keratinocytes (NHEK, 10(5)/75 microL) were
seeded. The xeno-LSE was used as a rejection target organ in vitro. Rejection was
achieved by the addition of human lymphocytes (10(6)/75 microL). At various
intervals of growth, control LSEs without lymphocytes (CON) and rejecting LSEs
with immunocytes (REJ) were analyzed. Slides were stained with hematoxylin &
eosin and examined under light microscopy. REJ xenocomposite LSEs showed classic
histologic signs of rejection. There was separation of the D-E junction with the
presence of dyskeratotic and necrotic cells with a concomitant inflammatory
infiltrate. The CON LSEs showed essentially normal dermis (collagen fibroblast
matrix) and keratinocytes. A significant finding was the separation of the D-E
junction in the absence of an inflammatory infiltrate. Previous studies have
shown that human keratinocytes can be grown with human fibroblasts that are
histologically similar to natural human skin. This discohesive nature of the
murine fibroblasts and human keratinocytes may represent an important
intercellular interaction associated with xeno-cellular interactions and is
worthy of further study. Furthermore, the ability to grow xeno-composite tissues
has profound implications in the face of organ donor shortages. They may
represent an eventual in vitro replacement of skin and even solid organs.
PMID- 9636443
TI - Genetic characteristics of anti-donor immunoglobulin G antibodies in the hamster
to-rat model of xenotransplantation.
PMID- 9636444
TI - Tacrolimus enhances the immunosuppressive effect of cyclophosphamide but not that
of leflunomide or mycophenolate mofetil in a model of discordant liver
xenotransplantation.
PMID- 9636445
TI - Controversies in heart and lung transplantation immunosuppression: tacrolimus
versus cyclosporine.
PMID- 9636446
TI - Effects of tacrolimus and cyclosporine on the coronary microcirculation after
heart transplantation: a prospective study with serial intracoronary flow
measurements.
PMID- 9636447
TI - Cytolytic induction therapy in heart and lung transplantation: the protagonist
opinion.
AB - From the studies analysed as well as based on our own experience, induction
therapy mainly with polyclonal cytolytic agents represents a helpful tool in the
individualised immunosuppressive approach, whereas monoclonal induction therapies
have to be discussed carefully. Although transplantation is also feasible without
cytolytic agents, certain patients at risk will further encourage the need for
this valuable therapy also in the future, where new immunosuppressants are
available. However, it is anticipated that the application should be conducted on
an individual patient basis to achieve optimal individual benefit.
PMID- 9636448
TI - Contribution of the inflammatory response to cardiac allograft rejection:
histopathologic analysis of serial endomyocardial biopsies.
PMID- 9636449
TI - Long-term outcome with the use of OKT3 induction therapy in heart transplant
patients: a single-center experience.
PMID- 9636450
TI - Use of intravenous immunoglobulin in sensitized LVAD recipients.
PMID- 9636451
TI - Pharmacokinetics of tacrolimus (FK506) in primary orthotopic heart transplant
patients.
PMID- 9636452
TI - Clinical outcomes associated with conversion to tacrolimus-based
immunosuppression in pediatric cardiac transplantation.
PMID- 9636453
TI - Posttransplant lymphoproliferative disorders in cardiac transplant patients.
PMID- 9636454
TI - Unusual course of T-cell lymphoproliferative disorder in a cardiac transplant
patient.
PMID- 9636455
TI - Survival of heart transplant recipients with cyclosporine-induced renal
insufficiency.
PMID- 9636456
TI - High incidence and clinical course of aggressive skin cancer in heart transplant
patients: a single-center study.
PMID- 9636457
TI - Effect of allopurinol on the metabolism of azathioprine in heart transplant
patients.
PMID- 9636458
TI - Does preexisting elevated pulmonary vascular resistance (transpulmonary gradient
> 15 mm Hg or > 5 wood) predict early and long-term results after orthotopic
heart transplantation?
PMID- 9636459
TI - Rapid trabecular bone loss after cardiac transplantation using FK506 (tacrolimus)
based immunosuppression.
PMID- 9636460
TI - Medium-term outcome of tacrolimus immunosuppression following rejection or graft
dysfunction in heart transplant patients.
PMID- 9636461
TI - Evidence for a type 2 bias in the CD8+ T-cell response to Epstein-Barr virus
following heart transplantation.
PMID- 9636462
TI - Combined chronic administration of methotrexate and cyclosporine A following
cardiac ongoing rejection.
PMID- 9636463
TI - Natural history and the clinical importance of early and late grade 2 cellular
rejection following cardiac transplantation.
PMID- 9636464
TI - Effect of Sandimmune cyclosporine on renal blood flow and function in heart
transplant recipients.
PMID- 9636465
TI - Risks and benefits of withdrawing cyclosporine from the long-term
immunosuppression regimen of heart and heart-lung transplant recipients.
PMID- 9636466
TI - Clinical impact of Neoral in heart transplantation.
PMID- 9636467
TI - Can anti-HLA antibody analyses postcardiac transplantation predict acute
allograft rejection and survival?
PMID- 9636468
TI - Neoral conversion in stable thoracic transplant patients leads to dose reduction.
PMID- 9636469
TI - Changes in T-cell subsets after renal transplantation in nonimmunosuppressed
baboons.
PMID- 9636470
TI - Depressed expression of CD 28 antigen on lymphocytes in long-term kidney
transplant patients.
PMID- 9636471
TI - Immunoglobulin class switch of posttransplant panel reactive antibody and the
impact on kidney allograft outcome.
PMID- 9636472
TI - Novel concept for easy quantification of posttransplant immunocompetence.
PMID- 9636473
TI - Predicting factors for long-term results of OKT3 therapy in steroid-resistant
acute rejection following cadaveric renal transplantation.
PMID- 9636474
TI - Late acute rejection is more prevalent among African-American renal allograft
recipients and is frequently associated with allograft loss.
PMID- 9636475
TI - Effect of antirejection therapy on HLA-DR antigens and ICAM-1 expression on
parenchymal cells as monitored by fine needle aspiration biopsy.
PMID- 9636476
TI - Primary therapy with OKT3 for biopsy-proven acute renal allograft rejection.
PMID- 9636477
TI - Importance of degree of eosinophilia in inflammatory infiltrates within renal
allografts in the response to immunosuppressive treatment.
PMID- 9636478
TI - Limited sampling strategy for the determination of mycophenolic acid area under
the curve in pediatric kidney recipients. German Study Group on MMF Therapy in
Pediatric Renal Transplant Recipients.
PMID- 9636480
TI - Selective CellCept therapy in high-risk renal transplant recipients.
PMID- 9636479
TI - Therapeutic drug monitoring of mycophenolic acid: comparison of HPLC and
immunoassay reveals new MPA metabolites.
PMID- 9636481
TI - Conversion to mycophenolate mofetil for chronic progressive deterioration of
renal allograft function: first clinical experiences in 44 patients.
PMID- 9636482
TI - Relation of mycophenolic acid trough levels and adverse events in kidney
allograft recipients.
PMID- 9636483
TI - Use of mycophenolate mofetil in patients with chronic cyclosporine
nephrotoxicity.
PMID- 9636484
TI - Area under the curve of Neoral and chronic use of mycophenolate mofetil.
PMID- 9636485
TI - Abbreviating area under the curves further: a practical approach to monitoring
extended pharmacokinetics with Neoral.
PMID- 9636486
TI - Randomized trial to evaluate the use of increasing the steroid dose during
conversion from cyclosporine to azathioprine.
PMID- 9636487
TI - Cyclosporine-related hemolytic-uremic syndrome in kidney graft recipients:
clinical and histomorphologic evaluation.
PMID- 9636488
TI - Is cyclosporine toxic to the transplanted kidney with acute tubular necrosis?
PMID- 9636489
TI - Causes of long-term renal allograft failure: no chronic rejection at three years.
PMID- 9636490
TI - Successful therapy of chronic renal allograft failure by enhanced
immunosuppression.
PMID- 9636491
TI - Role of acute rejection in chronic rejection.
PMID- 9636492
TI - Effect of tacrolimus on the outcome of renal transplantation with donor-specific
blood transfusion.
PMID- 9636493
TI - FK 506 as primary immunosuppressive therapy in renal transplantation.
PMID- 9636494
TI - Tacrolimus (FK 506) in kidney transplantation: three-year survival results of the
US multicenter, randomized, comparative trial. FK 506 Kidney Transplant Study
Group.
PMID- 9636495
TI - Tacrolimus therapy for ABO-incompatible kidney transplantation.
PMID- 9636496
TI - Primary low-dose tacrolimus immunosuppressive prophylaxis for high-risk kidney
transplant recipients.
PMID- 9636497
TI - Long-term results of living kidney transplantation under tacrolimus
immunosuppression: a single-center experience.
PMID- 9636498
TI - Long-term comparison of tacrolimus and cyclosporine-based immunosuppression in
kidney recipients with grafts from non-heart-beating cadaver donor.
PMID- 9636499
TI - Preoperative induction with tacrolimus does not have a detrimental effect on
primary graft function in adult cadaveric renal transplantation.
PMID- 9636500
TI - Use of tacrolimus as the primary immunosuppression after renal transplant in
Native Americans and Hispanics.
PMID- 9636501
TI - Tacrolimus therapy for refractory acute renal allograft rejection: a 4-year
experience with an aggressive approach.
PMID- 9636502
TI - Combining FK 506 and mycophenolate mofetil for the treatment of acute
corticosteroid-resistant rejection following kidney transplantation: a new
therapeutic concept.
PMID- 9636503
TI - Tacrolimus rescue therapy in late rejection after renal transplantation: outcome
after 18 months.
PMID- 9636504
TI - Improvement of nephrotoxicity, hypertension, and lipid metabolism after
conversion of kidney transplant recipients from cyclosporine to tacrolimus.
PMID- 9636505
TI - Elective conversion of patients from cyclosporine to tacrolimus for
hypertrichosis.
PMID- 9636506
TI - Conversion from cyclosporine to tacrolimus in renal allograft recipients with
chronic graft nephropathy: preliminary report.
PMID- 9636507
TI - Conversion from Neoral (cyclosporine) to tacrolimus of kidney transplant
recipients for gingival hyperplasia or hypertrichosis.
PMID- 9636508
TI - Reversal of delayed hyperacute renal allograft rejection with a tacrolimus-based
therapeutic regimen.
PMID- 9636509
TI - Tacrolimus for steroid- and OKT3-resistant rejection in kidney recipients.
PMID- 9636510
TI - Cyclosporine to tacrolimus: effect on hypertension and lipid profiles in renal
allografts.
PMID- 9636511
TI - Tacrolimus for rescue of refractory renal allograft rejection.
PMID- 9636512
TI - Factors affecting the pharmacokinetics of tacrolimus in the first year after
renal transplantation. European Tacrolimus Multicentre Renal Study Group.
PMID- 9636513
TI - Influence of hepatitis C virus infection on FK 506 blood levels in renal
transplant patients.
PMID- 9636514
TI - Tacrolimus dosing requirements in diabetic and nondiabetic patients calculated
from pretransplantation data.
PMID- 9636515
TI - The effect of breakfast on the oral bioavailability of tacrolimus in diabetic and
nondiabetic patients before transplantation.
PMID- 9636516
TI - Effect of breakfast on the oral bioavailability of tacrolimus and changes in
pharmacokinetics at different times posttransplant in renal transplant
recipients.
PMID- 9636517
TI - Specificity of therapeutic drug monitoring of tacrolimus in kidney transplant
patients.
PMID- 9636518
TI - Decreasing pancreatic toxicity of tacrolimus by dosage reduction.
PMID- 9636519
TI - Early posttransplantation renal hemodynamics in FK 506-treated kidney recipients
with or without prior induction therapy.
PMID- 9636520
TI - Influence of early FK 506 trough levels on glomerular hemodynamics at 3 months in
kidney transplant recipients.
PMID- 9636521
TI - Pharmaco-economic study of FK 506 (Prograf) and cyclosporine A Neoral in
cadaveric renal transplantation.
PMID- 9636522
TI - FK 506 and mycophenolate mofetil in renal transplant recipients: six-month
results of a multicenter, randomized dose ranging trial. FK 506 MMF Dose-Ranging
Kidney Transplant Study Group.
AB - The effective dose of MMF with FK 506 has not been previously studied in a
prospective, randomized, controlled setting. In the present study, we evaluated
two different daily doses of MMF (1 and 2 g) and compared it to the historically
conventional therapy of AZA. At 6 months post-transplant, we found no significant
difference in the incidence of acute rejection between the AZA group and the MMF
1 g group. However, patients who started on MMF 2 g/d had significantly delayed
and lower incidence of acute rejection as compared to the other two groups. We
found that patients who were initiated on MMF 2 g frequently had their dose
lowered, primarily for gastrointestinal or hematologic symptoms; by 6 months
after-transplant, patients in the MMF 2 g group had a mean dose of 1.5 g. It is
unclear from this study if initiating patients on MMF 1.5 g in combination with
FK 506 would be as effective as initiating a patient on MMF 2 g. Further studies
of the combination of FK 506 and MMF in kidney transplant recipients to further
define the optimal dosing regimen are warranted. In summary, the combination of
FK 506 and MMF is well-tolerated, safe, and effective in cadaveric kidney
transplant recipients.
PMID- 9636523
TI - Co-administration of tacrolimus and mycophenolate mofetil in cadaveric renal
transplant recipients.
PMID- 9636524
TI - Lipoprotein patterns in renal transplant patients: a comparison between FK 506
and cyclosporine A patients.
PMID- 9636525
TI - Prospective randomized study comparing FK 506 (Prograft) and cyclosporine A
(Neoral) as primary immunosuppression in cadaveric renal transplants at a single
institution: interim report of the first 80 cases.
PMID- 9636526
TI - Meta-analysis of FK 506 and mycophenolate mofetil refractory rejection trials in
renal transplantation. Refractory Rejection Meta-Analysis Study Group.
PMID- 9636527
TI - Pharmacokinetics of FK 506 and mycophenolic acid after the administration of a FK
506-based regimen in combination with mycophenolate mofetil in kidney
transplantation.
PMID- 9636528
TI - Long-term steroid side effects in renal transplantation need a safe steroid
withdrawal: a single-center experience.
PMID- 9636529
TI - Renal allograft survival can be predicted by histomorphometric assessment of
extracellular matrix in 6-month protocol biopsies.
PMID- 9636531
TI - Differences between compliers and partial compliers: a multicenter study.
PMID- 9636530
TI - Therapy of hyperlipidemia with lovastatin in kidney transplant patients on
cyclosporine A immunosuppression: three-year experience.
PMID- 9636532
TI - Is long-term chronic immunosuppression therapy detrimental in hepatitis C virus
positive renal transplant patients?
PMID- 9636533
TI - Failure of ganciclovir prophylaxis of primary cytomegalovirus disease in
immunologic high-risk recipients.
PMID- 9636534
TI - Prediction of early graft function in renal transplantation using a computer
neural network.
PMID- 9636535
TI - Cytomegalovirus infection and prophylaxis in renal transplantation: financial
considerations.
PMID- 9636536
TI - Etiology of early renal allograft dysfunction after live donor renal
transplantation.
PMID- 9636537
TI - Significance of serial biopsies after renal allograft in children.
PMID- 9636538
TI - Influence of immunosuppression in HTLV-1-positive renal transplant recipients.
PMID- 9636539
TI - Stabilization of bone mass after renal transplant with preemptive care.
PMID- 9636540
TI - Reduced severity of acute rejection in hepatitis C virus positive renal allograft
recipients: are milder immunosuppressive regimens advisable?
PMID- 9636541
TI - Placebo-controlled study of a humanized anti-TAC monoclonal antibody in dual
therapy for prevention of acute rejection after renal transplantation.
PMID- 9636542
TI - Graft-versus-host antibody reactions in ABO unmatched renal transplants.
PMID- 9636543
TI - Risk of acute cellular rejection after azathioprine withdrawal in stable renal
allograft recipients on cyclosporine, azathioprine, and prednisone.
PMID- 9636544
TI - ABO incompatible kidney transplantation on triple therapy compared with quadruple
therapy.
PMID- 9636545
TI - Preoperative induction therapy with oral cyclosporine for recipients of living
related renal transplants.
PMID- 9636546
TI - Low incidence of acute rejection in kidney grafts treated with initial quadruple
therapy: a retrospective analysis comparing two ATGs.
PMID- 9636547
TI - Pre- versus intraoperative application of glucocorticosteroids as inductive
therapy in renal transplantation.
PMID- 9636548
TI - Polyclonal antilymphocyte sera induce immune activation in human renal allograft
recipients.
PMID- 9636549
TI - ATGAM versus OKT3 induction therapy in cadaveric kidney transplantation: patient
and graft survival, CD3 subset, infection, and cost analysis.
PMID- 9636550
TI - Experience with azathioprine withdrawal after simultaneous kidney-pancreas
transplantation.
PMID- 9636551
TI - Effect of race and immunosuppression in renal transplantation: three-year
survival results from a US multicenter, randomized trial. FK506 Kidney Transplant
Study Group.
PMID- 9636552
TI - Demographic considerations in tacrolimus pharmacokinetics.
PMID- 9636553
TI - Donor bone marrow infusion in renal transplantation.
PMID- 9636555
TI - Humanized, nonmitogenic OKT3 antibody, huOKT3 gamma(Ala-Ala): initial clinical
experience.
PMID- 9636554
TI - Adjuvant bone marrow infusion in clinical organ transplant recipients.
PMID- 9636556
TI - Bone marrow augmentation in renal transplant recipients.
PMID- 9636557
TI - Outcome after steroid withdrawal in renal transplant patients receiving
tacrolimus-based immunosuppression.
PMID- 9636558
TI - Corticosteroid cessation 1 week following renal transplantation using
tacrolimus/mycophenolate mofetil based immunosuppression.
PMID- 9636559
TI - Steroid withdrawal in renal transplant recipients: pro point of view.
AB - Steroid-free immunosuppression remains an attractive goal in an era in which the
transplant community should be promoting long-term allograft survival by reducing
cardiovascular risk and maximizing long-term patient survival. In the
cyclosporine era, the risks of steroid withdrawal outweighed the benefits of
steroid withdrawal in a substantial minority of patients. A number of new
immunosuppressants may prove to be more steroid sparing than cyclosporine alone
and promise to increase the safety of steroid-free immunosuppression for renal
transplant recipients.
PMID- 9636560
TI - Oral ganciclovir in the prevention of cytomegalovirus infection in postkidney
transplant "CMV at risk" recipients: a controlled, comparative study of two
regimens (750 mg Bid and 500 mg Bid).
PMID- 9636561
TI - An exploratory analysis of prognostic factors for patient outcome during the
first year following renal transplantation. European Tacrolimus Multicentre Renal
Study Group.
PMID- 9636562
TI - Three-year follow-up of low dose tacrolimus oral therapy after liver
transplantation: a single-centre experience.
PMID- 9636563
TI - Tacrolimus (FK506)-based dual versus triple therapy following liver
transplantation.
PMID- 9636564
TI - One hundred children treated with tacrolimus after primary orthotopic liver
transplantation.
PMID- 9636565
TI - Long-term comparison of tacrolimus versus cyclosporine in liver transplantation.
The US FK Study Group.
PMID- 9636566
TI - Renal function in primary liver transplant recipients receiving neoral
(cyclosporine) versus prograf (tacrolimus).
AB - Immunosuppressive efficacy of Neoral and Prograf following primary hepatic
transplantation was comparable. Incidence of rejection episodes, infectious
complications, hypertension, and postoperative diabetes mellitus was comparable.
Although clinical use of both immunosuppressants was associated with early
compromise in renal function, no progressive renal dysfunction was observed.
PMID- 9636567
TI - Liver transplantation under tacrolimus in infants, children, adults, and seniors:
long-term results, survival, and adverse events in 1000 consecutive patients.
PMID- 9636568
TI - Comparison of tacrolimus with neoral as primary immunosuppression in hepatitis C
patients after liver transplantation.
PMID- 9636569
TI - Successful use of tacrolimus for initial rejection episodes after liver
transplantation.
PMID- 9636570
TI - FK506 for primary and rescue therapy following liver transplantation.
PMID- 9636571
TI - Rescue FK506 therapy for acute rejection and early chronic rejection after liver
transplantation: report of 14 cases.
PMID- 9636572
TI - Improved immunosuppression with combination tacrolimus (FK506) and mycophenolic
acid in orthotopic liver transplantation.
PMID- 9636573
TI - Tacrolimus and mycophenolate mofetil in clinical liver transplantation:
experience with a steroid-sparing concept.
PMID- 9636574
TI - Immunosuppression using tacrolimus, mycophenolate, and prednisone following
orthotopic liver transplantation: a single-center experience.
PMID- 9636575
TI - Treatment of cyclosporine-related adverse effects by conversion to tacrolimus
after liver transplantation: long-term results.
PMID- 9636576
TI - Early use and oral absorption of cyclosporine neoral after liver transplantation.
PMID- 9636577
TI - Cyclosporine monotherapy in long-term pediatric liver transplant recipients.
PMID- 9636579
TI - Reduced acute rejection and side effects with neoral in liver transplantation.
PMID- 9636578
TI - Low rejection rate after hepatic transplantation achieved with a cyclosporine
based quadruple immunosuppressive regimen.
PMID- 9636580
TI - Experience with neoral cyclosporine through the oral route in liver
transplantation.
PMID- 9636581
TI - Cyclosporine versus cyclosporine microemulsion in pediatric liver transplant
recipients.
PMID- 9636582
TI - Lower incidence of liver graft rejection in patients on diltiazem plus
cyclosporine therapy.
PMID- 9636583
TI - Comparison of quadruple induction including ATG or IL-2R antibody with FK506
based therapy after liver transplantation.
PMID- 9636584
TI - Successful prednisone withdrawal after living-related liver transplantation.
PMID- 9636585
TI - Risk and benefit of antibody induction therapy in combination with tacrolimus
immunosuppression after liver transplantation.
PMID- 9636586
TI - A randomized trial comparing anti-interleukin-2 receptor antibody and placebo for
immunosuppressive therapy after OLT.
PMID- 9636587
TI - Metabolic findings after liver transplantation within a randomised trial with or
without steroids.
PMID- 9636588
TI - The necessity for steroid induction or long-term maintenance after liver
transplantation: the argument against.
PMID- 9636589
TI - Effect of CsA versus FK 506 on insulin sensitivity and insulin response using a
modeling technique.
PMID- 9636590
TI - In vitro generation of tacrolimus metabolites and their detection in whole blood.
PMID- 9636591
TI - Bioequivalence of a new strength tacrolimus capsule under development.
PMID- 9636592
TI - Optimal time points for the prediction of the area-under-the-curve in liver
transplant patients receiving tacrolimus.
PMID- 9636593
TI - Cyclosporine peak levels provide a better correlation with the area-under-the
curve than trough levels in liver transplant patients treated with neoral.
PMID- 9636594
TI - Does initial graft function influence the outcome after liver transplantation?
PMID- 9636595
TI - Impact of immunosuppression in liver transplantation across a positive
crossmatch.
PMID- 9636596
TI - Indications for mycophenolate mofetil therapy in hepatitis C-patients undergoing
liver transplantation.
PMID- 9636597
TI - Retransplantation for recurrent hepatitis C following tacrolimus or cyclosporine
immunosuppression.
PMID- 9636598
TI - Immunosuppression withdrawal for treatment of severe infections in liver
transplantation.
PMID- 9636599
TI - Immunosuppression and incidence of opportunistic pneumonias after liver
transplantation.
PMID- 9636600
TI - Clinical and radiological features of two cases of tacrolimus-related posterior
leukoencephalopathy in living related liver transplantation.
PMID- 9636601
TI - Living related liver transplantation for patients with renal failure.
PMID- 9636602
TI - Is liposomal amphotericin B (ambisome) an effective prophylaxis of mycotic
infections after liver transplantation?
PMID- 9636603
TI - De novo cancer after orthotopic liver transplantation.
PMID- 9636604
TI - Lymphoproliferative disease after liver transplantation: primary biliary
localization.
PMID- 9636605
TI - Hypercholesterolemia in long-term survivors of liver transplantation: a
comparison between cyclosporine and FK 506.
PMID- 9636606
TI - Donor-recipient sex matching and posttransplant malignancies after induction
therapy in hepatic transplantation.
PMID- 9636607
TI - Incidence of acute rejection in African-American liver transplant recipients.
PMID- 9636608
TI - Influence of immunosuppression on patient outcome after liver transplantation.
PMID- 9636609
TI - Protocol liver biopsies: the case in favour.
PMID- 9636610
TI - The cost of rejection in liver allograft recipients.
PMID- 9636611
TI - Cost of liver transplantation using tacrolimus.
PMID- 9636612
TI - Conversion to tacrolimus (FK506) from cyclosporine after orthotopic lung
transplantation.
PMID- 9636613
TI - FK506 rescue therapy in lung transplantation.
PMID- 9636614
TI - Comparison of neoral and sandimmun cyclosporines for de novo lung transplantation
in cystic fibrosis patients.
PMID- 9636615
TI - Cyclosporine A-associated thrombotic thrombocytopenic purpura following lung
transplantation.
PMID- 9636616
TI - Mycophenolate mofetil in lung transplantation.
PMID- 9636617
TI - ATG induction therapy and the incidence of bronchiolitis obliterans after lung
transplantation: does it make a difference?
PMID- 9636618
TI - Clinical use and bioavailability of tacrolimus in heart-lung and double lung
transplant recipients with cystic fibrosis.
PMID- 9636619
TI - Isolated lung transplantation for end-stage pulmonary disease.
PMID- 9636620
TI - Prevalence of malignancies after lung transplantation.
PMID- 9636621
TI - Does cyclosporin promote the secretion of transforming growth factor-beta 1
following pulmonary transplantation?
PMID- 9636622
TI - National transplantation Pregnancy Registry: outcomes of pregnancies in lung
recipients.
PMID- 9636623
TI - Tacrolimus/mycophenolate mofetil/steroid-based immunosuppression after pancreas
kidney transplantation with single shot antithymocyte globulin.
PMID- 9636624
TI - Use of intravenous tacrolimus to reverse vascular rejection in kidney and
simultaneous kidney-pancreas transplantation.
PMID- 9636625
TI - Tacrolimus/mycophenolate provides superior immunosuppression relative to
neoral/mycophenolate in synchronous pancreas-kidney transplantation.
PMID- 9636626
TI - Long-term kidney and pancreas function with tacrolimus immunosuppression
following simultaneous kidney and pancreas transplantation.
PMID- 9636627
TI - Use of tacrolimus and mycophenolate mofetil for pancreas-kidney transplantation
with or without OKT3 induction.
PMID- 9636628
TI - Superior efficacy of oral ganciclovir over oral acyclovir for cytomegalovirus
prophylaxis in kidney-pancreas and pancreas alone recipients.
PMID- 9636629
TI - Sequential pancreas after kidney transplantation: is anti-lymphocyte induction
therapy needed?
PMID- 9636630
TI - Low-dose OKT3 treatment for rejection/induction in kidney and kidney-pancreas
transplantation.
PMID- 9636632
TI - Antibody induction therapy in pancreas transplantation.
PMID- 9636631
TI - Evidence for microchimerism in peripheral blood, bone marrow, and skin following
donor bone marrow/kidney-pancreas transplantation at 3 years.
PMID- 9636633
TI - Late acute rejection episodes after vascularized pancreas transplantation.
PMID- 9636634
TI - Mycophenolate mofetil versus azathioprine in simultaneous pancreas-kidney
transplant recipients on cyclosporine.
PMID- 9636635
TI - Long-term outcomes in simultaneous kidney-pancreas transplant recipients.
PMID- 9636636
TI - Small bowel transplantation alone or with the liver in children: changes by using
FK506.
PMID- 9636637
TI - Immunosuppressive agents: recent developments in molecular action and clinical
application.
PMID- 9636638
TI - Future challenges in immunosuppression.
PMID- 9636639
TI - Basic science aspects of chronic rejection: induction of protective genes to
prevent development of transplant arteriosclerosis.
PMID- 9636640
TI - Chronic rejection.
PMID- 9636641
TI - The "infectious" tolerance pathway in organ allograft recipients.
PMID- 9636642
TI - Tacrolimus as a primary immunosuppressive therapy in cadaveric renal
transplantation: five years' experience at a single center.
PMID- 9636643
TI - Mucin functions and expression in mammalian reproductive tract tissues.
PMID- 9636644
TI - BC1 RNA protein particles in mouse brain contain two y-,h-element-binding
proteins, translin and a 37 kDa protein.
AB - Neural BC1 RNA is distributed in dendrites in the form of ribonucleoprotein
particles (RNP). Recently, Han et al. reported that testis-brain RNA-binding
protein (the mouse homologue of Translin), known to be a translational repressor,
links a subset of mRNAs to microtubules (MTs) through binding to their y-,h
sequence elements. We found that similar elements are also present in BC1 RNA.
Therefore, it is possible that they also act as cis-elements, together with their
transacting proteins, and control the transport of BC1 RNA along dendritic MTs.
In this study, we demonstrated that two y-,h-element-binding proteins copurified
with BC1 RNP. One was identified as mouse Translin and the other was a 37 kDa
protein. This macromolecular assembly may constitute a transport particle for BC1
RNA. It is also possible that BC1 RNP or Translin itself may play a regulatory
role(s) in the translation of mRNAs within dendrites.
PMID- 9636645
TI - Protective protein/cathepsin A loss in cultured cells derived from an early
infantile form of galactosialidosis patients homozygous for the A1184-G
transition (Y395C mutation).
AB - Galactosialidosis is a human autosomal recessive lysosomal storage disease caused
by a genetic defect of protective protein/cathepsin A (PPCA). The patients in a
Japanese family with the severe early-infantile form of galactosialidosis were
revealed to be homozygous for the A1184-G transition in the PPCA gene in both
alleles, which leads to the Y395C substitution. The acid carboxypeptidase
(cathepsin A) and lysosomal neuraminidase activities were markedly decreased in
cultured fibroblasts and chorionic villus cells derived from the patients,
although the decrease in beta-galactosidase activity was less. Immunoblot and
immunocytochemical analyses showed that neither the precursor nor the mature form
of the PPCA gene product was present in the cultured cells. The Y395C mutation
was revealed to cause the loss of the translated product, that determines the
severity of the clinical phenotype.
PMID- 9636646
TI - Modulation of the growth of Plasmodium falciparum in vitro by protein
serine/threonine phosphatase inhibitors.
AB - To elucidate the physiological roles of the protein serine/threonine phosphatases
of P. falciparum, first we identified and characterized phosphatase activities of
Plasmodium falciparum enzymologically and pharmacologically. We have demonstrated
that P. falciparum possesses phosphatase-1-like activities predominantly over
phosphatase-2A-like activities, while erythrocytes possess mainly phosphatase-2A
like activities. Then, we examined the effects of okadaic acid and calyculin A,
potent inhibitors of protein phosphatase 1 and 2A, on the growth of P. falciparum
in vitro. Both of the drugs inhibited parasite growth dose dependently. The
manner of growth inhibition by calyculin A and okadaic acid suggested that these
drugs inhibit parasite growth mainly by inhibiting parasite phosphatase-1-like
activities. Both drugs were shown to inhibit the growth of three different
developmental stages of parasites--ring forms, trophozoites, and schizonts--and
inhibit trophozoites the most. This is the first report on P. falciparum protein
serine/threonine phosphatase activities, which are essential to regulate the
erythrocytic stage of parasite growth.
PMID- 9636647
TI - Tissue-specific involvement of multiple mitochondrial DNA deletions in familial
mitochondrial myopathy.
AB - It is still uncertain how deleted mitochondrial DNA (mtDNA) is distributed to
each tissue during development, although deletions of mtDNA have been extensively
observed in various pathologic conditions. This paper presents two Japanese
siblings with progressive external ophthalmoplegia exhibiting multiple mtDNA
deletions. In one patient, similar multiple mtDNA deletions were found in
skeletal muscle specimens as well as in the spinal cord but not in the
myocardium, liver or leukocytes. A similar deletion pattern was found in the
skeletal muscle but not in the leukocytes of the other patient. The results
suggest the complex mechanism to generate, expand and eliminate the deleted mtDNA
in humans.
PMID- 9636648
TI - A steroidogenic factor-1 binding element is essential for basal human ACTH
receptor gene transcription.
AB - We have previously shown that the promoter of the human ACTH receptor (ACTH-R)
contains, at -35 bp, a binding site for the steroidogenic factor 1 (SF-1), an
orphan nuclear receptor which could be responsible for the transcriptional
activity of this promoter. In the present study, electrophoretic mobility shift
assays demonstrated that the sequence -43/-19 bound the SF-1 protein present in
the nuclear extracts of adrenocortical cells. Mutation of the SF-1 binding site
markedly reduced (40%) the basal transcription of the reporter gene in Y-1 cells
transfected with the mutated p(-56/+22)GH construct compared to the wild-type
construct. These results demonstrate that the SF-1 binding element present in
this fragment is required for the basal promoter activity of the human ACTH-R
gene. In addition, other binding elements located upstream from this
characterized SF-1 binding site are involved in the full basal promoter activity
of the human ACTH-R since transfection studies with a longer p(-1017/+22)GH
construct resulted in a higher GH release than with the p(-56/+22)GH construct.
PMID- 9636649
TI - Expression of endoglin mRNA and protein in human vascular smooth muscle cells.
AB - Endoglin, the gene linked to the autosomal dominant vascular disorder hereditary
hemorrhagic telangiectasia type 1 (HHT1), encodes a 95-kDa membrane-bound
proteoglycan which binds TGF beta 1 and regulates signaling via the type I and II
TGF beta receptors on the surface of vascular endothelial cells. Using reverse
transcription polymerase chain reaction (RT-PCR) and Northern blot analysis we
have shown that endoglin mRNA is expressed in both cultured human VSMCs and VSMCs
freshly isolated from human aortas. Northern blot analysis was also used to
demonstrate that endoglin expression decreased in serum-stimulated cultured human
VSMCs but could be maintained by exogenous TGF beta 1. Endoglin protein
expression in human VSMCs was shown by immunocytochemistry. These data, the first
describing the existence of endoglin in VSMCs, suggest that through regulating
TGF beta 1 signaling endoglin may mediate the effects of TGF beta 1 on VSMC
behavior in vitro and in vivo.
PMID- 9636650
TI - Endothelial cells differentially express functional CXC-chemokine receptor-4
(CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines.
AB - Analysis of endothelial cell (EC) chemokine receptor expression by RT-PCR
revealed that EC essentially do not express CC-chemokine receptors whereas they
express all known CXC-chemokine receptors. Endotheliotropic functions of ligands
for CXCR-1, CXCR-2, and CXCR-3 have previously been described. We have
consequently performed a detailed analysis of endothelial CXCR-4 expression. CXCR
4 is constitutively expressed by quiescent, resting EC. Cytokine stimulation
revealed that bFGF upregulates endothelial CXCR-4 expression, whereas TNF alpha
downregulates endothelial CXCR-4 expression. Expression of CXCR-4 mRNA as well as
protein is also upregulated in autocrine activated, migrating bovine aortic
endothelial cells (BAEC). Furthermore, migrating BAEC preferentially present CXCR
4 on the cell surface as evidenced by cytochemistry and FACS analysis. Lastly,
the monospecific CXCR-4 ligand SDF-1 was found to act as a potent inducer of EC
chemotaxis. In summary, the data indicate that the CXCR-4/SDF-1 receptor ligand
interaction may be an important regulator of activated endothelial cell functions
as they occur during vascular remodeling and angiogenesis.
PMID- 9636651
TI - Insulin-like growth factor I stimulates proliferation and Fas-mediated apoptosis
of human osteoblasts.
AB - In vitro studies have shown that insulin-like growth factor I (IGF-I) is a potent
growth factor for osteoblasts, although both bone formation and resorption are
upregulated by IGF-I in vivo. To understand the difference in the action of IGF-I
observed in vitro and in vivo experiments, we examined the effect of IGF-I on the
proliferation and Fas-mediated apoptosis of human osteoblasts in vitro. Human
osteoblastic cell line MG63 and human primary osteoblast-like cells obtained from
biopsy specimens were used as human osteoblasts. Cells were cultured with or
without various concentrations of IGF-I followed by determination of the
proliferative response and Fas-mediated apoptosis. IGF-I dose dependently
stimulated the proliferation of cultured human osteoblasts. Both Fas expression
and the degree of anti-Fas IgM-induced apoptosis of human osteoblasts was also
augmented by IGF-I. Furthermore, the cytotoxicity of Fas ligand (FasL) cDNA
transformants against human osteoblasts was increased when IGF-I-stimulated
osteoblasts were used as target cells, indicating that stimulation of IGF-I
increased functional Fas expression on human osteoblasts as well as their
proliferation. The addition of DEVD-CHO, a specific inhibitor of CPP32, to the
culture resulted in a significant inhibition of Fas-mediated apoptosis of both
unstimulated and IGF-I-stimulated osteoblasts, although it did not affect the
proliferative response or Fas expression. Our data suggest that activation of
CPP32 is necessary for Fas-mediated apoptosis of human osteoblasts, and treatment
of IGF-I increased this signaling pathway. In contrast, regulation of
proliferation and Fas expression of the cells were probably not affected by CPP32
activation. Our results suggest that IGF-I acts on cultured human osteoblasts by
increasing their proliferation and induction of Fas-mediated apoptosis by
neighbouring FasL+ cells such as osteoclasts, thus probably functioning as a
local coupling factor in the bone in vivo, stimulating both bone formation and
resorption.
PMID- 9636653
TI - Co-amplification of nuclear pseudogenes and assessment of heteroplasmy of
mitochondrial DNA mutations.
AB - The potential co-amplification of actual mtDNA and nucleus-embedded mtDNA
sequences was studied for the mtDNA domains encompassing the major disease
causing mtDNA mutations. By using two different cell lines devoid of mtDNA (rho
degree cell lines), it is shown that nucleus-embedded mtDNA sequences readily co
amplified with most of the mtDNA domains encompassing disease-causing mtDNA
mutations. The selection of mtDNA primers for specificity on rho degree cells
constitutes a simple procedure to avoid such co-amplification. It appears
mandatory prior to quantify mtDNA mutations, especially when delivering prenatal
diagnosis or predictive genetic advise.
PMID- 9636652
TI - Identification and distribution of mRNA encoding the Y1, Y2, Y4, and Y5 receptors
for peptides of the PP-fold family in the rat intestine and colon.
AB - Peptide YY (PYY), neuropeptide Y (NPY) and pancreatic polypeptide (PP) are
structurally related peptides which have potent antisecretory effects in small
and/or large intestines. Receptors mediating these effects are still unknown with
the exception of a PYY-preferring receptor expressed in small intestinal crypts.
In the present study, expression of recently cloned Y1, Y2, and Y5 receptors
which have similar affinity for PYY and NPY and Y4 receptors which have a high
affinity for PP was investigated in gut by RT-PCR analysis. The data show that
all Y receptors are expressed in small intestine and/or colon but with specific
distributions. Y1 receptors are only expressed in nonepithelial colonic tissue,
whereas Y2 and Y4 receptors are present in both epithelial and nonepithelial
tissue of the small or large intestine. In contrast, Y5 receptor expression
appears to be restricted to epithelial crypts of the small intestine and
nonepithelial tissue of colon. Sequencing of PCR products showed 100% identity
with the corresponding sequences of the cloned Y1, Y4, or Y5 receptors. The PCR
product obtained with Y2 primers from rat crypt cells showed 84% identity with
the cloned human Y2 receptor. These data indicate a wide distribution of Y
receptors in small intestine and colon. They also suggest that Y1, Y2, Y4, and Y5
receptors may be responsible for still unexplained effects of PYY, NPY, or PP on
secretion in small and large intestines.
PMID- 9636654
TI - Free radical-scavenging properties of olive oil polyphenols.
AB - Plants in the Mediterranean basin, such as vine and olive trees, have developed
an array of antioxidant defences to protect themselves from environmental stress.
Accordingly, the incidence of coronary heart disease and certain cancers is lower
in the Mediterranean area, where olive oil is the dietary fat of choice. As
opposed to other vegetable oils, extra virgin olive oil, which is obtained by
physical pressure from a whole fruit, is rich in phenolic components that are
responsible for the particular stability of the oil. We have investigated the
scavenging actions of some olive oil phenolics, namely hydroxytyrosol and
oleuropein, with respect to superoxide anion generation, neutrophils respiratory
burst, and hypochlorous acid. The low EC50S indicate that both compounds are
potent scavengers of superoxide radicals and inhibitors of neutrophils
respiratory burst: whenever demonstrated in vivo, these properties may partially
explain the observed lower incidence of CHD and cancer associated with the
Mediterranean diet.
PMID- 9636655
TI - Transcription factor NF-E2 is essential for the polyploidization of a human
megakaryoblastic cell line, Meg-J.
AB - Transcription factors regulating the process of megakaryocyte development remain
largely unclarified. To clarify them further, we used a human megakaryoblastic
cell line, Meg-J, which showed prominant polyploidization and augmented platelet
glycoprotein (GP) Ib expression after incubation with thrombopoietin (TPO, c-mpl
ligand) and K252a (an indolocarbasole derivative). Under these conditions, we
analyzed the expression of the transcription factors and observed that the
expression of NF-E2 p45, but not those of GATA-1, GATA-2, Tal-1/SCL, Evi-1, and
MafK, was increased after TPO and K252a stimulation. Gel-shift assay confirmed
the enhanced binding activity to the NF-E2 site. The abolishment of NF-E2 p45
with NF-E2 antisense oligomers inhibited TPO plus K252a-induced polyploidization.
These findings suggest that NF-E2 p45 is essential for the polyploidization of
megakaryocytic cells.
PMID- 9636656
TI - A hVti1 homologue: its expression depends on population doubling levels in both
normal and SV40-transformed human fibroblasts.
AB - A cDNA clone was isolated by differential colony hybridization from a cDNA
library prepared from life-extended SV40-transformed human fibroblasts. The
clone, tentatively named N-10, was 1272 bp in length coding for 232 amino acids.
Northern analysis revealed that the expression level of N-10 was increased in
normal senescent and life-extended SV40-transformed fibroblasts than in their
young counterparts but was not enhanced by growth arrest. The protein fused to
GFP (green fluorescent protein) localized in cytoplasmic granule. Enforced
expression of N-10 resulted in premature senescence in young fibroblasts. The
deduced amino acid sequence of N-10 was identical to the recently reported hVti1
gene except in one amino acid: Asp24(GAC) was ours and Asn24 (AAC) was reported.
Additional base differences were found, so we referred to our sequence as the
hVti1 homologue. As hVti1 protein was suggested to be involved in the vesicle
transport process, the homologue may be concerned with increased secretion of
extracellular matrix and various cytokines associated with cellular senescence.
PMID- 9636657
TI - Cloning and characterization of human estrogen receptor beta isoforms.
AB - Multiple transcripts which arise from the human estrogen receptor beta (ER beta)
gene have been characterized. Three full length isoforms of the hER beta gene,
designated hER beta 1-3, were identified in a testis cDNA library. An additional
two isoforms, designated hER beta 4 and hER beta 5, were identified by PCR
amplification from testis cDNA and from the MDA-MB 435 cell line. hER beta 1
corresponds to the previously described hER beta. All five isoforms diverge at a
common position within the predicted helix 10 of the ligand binding domain of hER
beta, with nucleotide sequences consistent with differential exon usage. The hER
beta isoform mRNAs displayed a differential pattern of expression in human
tissues and in tumor cell lines when analyzed by RT-PCR. Further characterization
of the three full length isoforms, hER beta 1-3, by in vitro band shift studies
indicated that the isoforms were able to form DNA-binding homodimers and
heterodimers with each other and with the ER alpha subtype.
PMID- 9636658
TI - The DNA-dependent protein kinase participates in the activation of NF kappa B
following DNA damage.
AB - The NFkB transcription factor is activated by diverse stimuli, including Ionizing
Radiation (IR) and the cytokine TNF alpha. The role of DNA-PK, a protein kinase
involved in the response to DNA damage, in the activation of NF kappa B by IR and
TNF alpha was examined. In M059K cells, which express DNA-PK, NF kappa B was
activated by both TNF alpha and IR. In M059J cells, which do not express DNA-PK,
IR did not activate NF kappa B, whereas TNF alpha induction of NF kappa B was
still observed. In HeLa cells, wortmannin, an inhibitor of DNA-PK, blocked the
induction of NF kappa B by IR but not by TNF alpha. DNA-PK also phosphorylated
the NF kappa B inhibitory proteins IkB-alpha and IkB-beta in vitro, and deletion
analysis demonstrated that DNA-PK phosphorylates 2 distinct regions of IkB-beta.
These results indicate that DNA-PK participates in the activation of NF kappa B
by IR but not by TNF alpha.
PMID- 9636659
TI - Arginase AI is upregulated in acute immune complex-induced inflammation.
AB - Previous studies have shown high arginase activity at inflammatory sites.
Arginase converts L-arginine to L-ornithine, sharing a common substrate with
nitric oxide synthase. It exists as two isoforms, AI and AII. While the function
of liver arginase (AI) in ureagenesis has been defined, the role and isoform of
arginase in cells without a complete urea cycle are unknown. We therefore
determined arginase isoform mRNA expression in glomerular acute immune complex
inflammation, and its cultured constituent cells. AI was induced in nephritic
glomeruli, and in mesangial cells stimulated with IL-4 and cAMP, and was present
in elicited neutrophils and macrophages. AII was constitutively expressed. Our
data strongly suggest that AI, thought to be restricted to the liver, accounts
for high arginase activity at inflammatory sites where it may limit high output
nitric oxide production and generate polyamines and proline essential for cell
proliferation and matrix production. This identification of AI in inflamed tissue
is an important step for understanding the consequences of increased arginase
activity.
PMID- 9636660
TI - The nucleus of HeLa cell contains tubular structures for Ca2+ signalling.
AB - It has long been assumed that Ca2+ are translocated from the cytosol to the cell
nucleus by a long distance to activate transcription machinery buried deep in the
nucleoplasm. However, this model has been recently challenged. When HeLa cells
were loaded with fluo-3, highly fluorescent spots of approximately 2 microns in
diameter were observed in the cell nucleus while the fluo-3 signals were low in
their neighbouring nucleoplasm as determined by confocal microscopy. These
fluorescent spots were devoid of but usually associated with chromatin on their
boundary. When cells were stimulated by ionomycin (1 microM), the fluo-3
fluorescence in these spots increased faster than that in their neighbouring
nucleoplasm. In another experiment, optical sections with hot spot(s) were used
to construct 3-D images to study the morphology of the hot spots. Views of
reconstruction from different angles indicated that the hot spots formed a
tubular structure with a connection to the nucleocytoplasmic interface. Moreover,
injection of calcium green-dextran (70 kDa), a Ca(2+)-sensitive indicator
conjugated with an inert molecule of large molecular size, into the cytosol leads
to a formation of signals also in a tubular shape inside the nucleoplasm. This
suggests that the 'channels' are real inside the nucleus and they are derived
from an invagination of the double-membraned nuclear envelope. Taken together,
our results indicate (1) tubular structures are found inside the cell nucleus;
(2) they are extended from the cytosol into the nucleus through the invagination
of the double membraned nuclear envelope; (3) molecules of molecular size up to
70 kDa could penetrate into these 'tunnels'; (4) Ca2+ can be released or
transported into the cell nucleus through these tubular structures after
ionomycin stimulation; and (5) the structures are usually associated with
chromatin.
PMID- 9636661
TI - Successful transplantation of genetically corrected DMD myoblasts following ex
vivo transduction with the dystrophin minigene.
AB - Myoblast transplantation and gene therapy are two promising therapeutical
approaches for the treatment of Duchenne Muscular Dystrophy (DMD). So far, both
strategies have met many hurdles, mainly because of immune reactions. In this
study, we investigated a third and novel strategy based on the combination of
these two basic ones, i.e., transplantation of genetically modified myoblasts. We
first derived a primary culture from a muscle biopsy of a young DMD patient (3
years old). Adenoviral-mediated dystrophin gene transfer into these DMD cultures
and expression of the dystrophin transgene were achieved in vitro. The transduced
cultures were then transplanted the same day in immunodeficient SCID mouse
muscles. Three weeks following the graft, many human dystrophin-positive fibers
were observed throughout sections of the injected muscles. However, many fibers
expressed human MHC antigens without expressing human dystrophin due to the low
percentage of infected primary muscle cells in vitro (even when a high MOI [400]
was used) and to a reduction and even to a complete loss of transgene copy number
during myoblast replication. From our results, we conclude that, although not at
a high proportion, (1) DMD primary myoblast cultures are infectable by
adenoviruses; (2) they can be efficiently transplanted back in a muscle, leading
to normal fusion of infected myoblasts with the host fibers; and (3) they can
correct the dystrophin deficiency in the host fibers by the expression of a mini
dystrophin transgene.
PMID- 9636662
TI - Cloning and expression pattern of chicken Pitx2: a new component in the SHH
signaling pathway controlling embryonic heart looping.
AB - Asymmetry along the left-right axis of the embryo is a vital feature of
vertebrate embryogenesis. In this study, we report the isolation and
characterization of a bicoid-related homeobox gene, cPitx2, which displays left
right asymmetric expression during early chick embryogenesis. Asymmetric
expression of cPitx2 is first detected at stage 7 and is restricted to mesodermal
tissues on the left side of the embryo including the left sided lateral mesoderm,
the left sided precardiac mesoderm, and the left half epimyocardium of the
primitive heart. cPitx2 is also detected in the presumptive blood islands and
endothelia of the embryonic blood vessels. Implantation of Sonic hedgehog (SHH)
protein soaked beads on the right side of embryos induced ectopic cPitx2
expression on that side. Based on these observations, we suggest that cPitx2 is a
component in SHH signaling pathway and plays a role in determining left-right
asymmetry and in vasculogenesis during avian embryogenesis.
PMID- 9636663
TI - A novel lectin with potent immunomodulatory activity isolated from both fruiting
bodies and cultured mycelia of the edible mushroom Volvariella volvacea.
AB - A novel lectin has been purified from the fruiting bodies as well as cultured
mycelia of the edible mushroom Volvariella volvacea. The lectin, designated as
VVL, was a homodimeric protein with a molecular weight of 32 kDa as demonstrated
by gel filtration and SDS-PAGE. VVL had no carbohydrate moiety, and its
hemagglutinating activity was inhibited by thyroglobulin but not by simple
carbohydrates such as monomeric or dimeric sugars. The immunomodulatory activity
of VVL was demonstrated by its potent stimulatory activity toward murine splenic
lymphocytes. VVL was also found to markedly enhance the transcriptional
expression of interleukin-2 and interferon-gamma by reverse transcriptase
polymerase chain reaction. As revealed by its N-terminal amino acid sequence, VVL
possessed a molecular structure distinct from other immunomodulatory proteins
previously reported in the same fungus.
PMID- 9636664
TI - A novel mitochondrial tRNA(Phe) mutation inhibiting anticodon stem formation
associated with a muscle disease.
AB - We have identified a novel mitochondrial (mt) DNA mutation in the tRNA(Phe)-gene
in a patient with an isolated mitochondrial myopathy. This T to C transition at
position 618 disrupts a strictly conserved base pair within the anticodon stem of
tRNA(Phe). Computer analysis showed that the affected base pair is essential for
anticodon stem formation of tRNA(Phe). The mutant mtDNA was heteroplasmic in
skeletal muscle (95% mutant) and peripheral blood cells (20% mutant) from the
patient but was undetectable in blood cells from his healthy sister. The patient
presented with ragged red fibers and reduced activities of complex I and complex
III in skeletal muscle. The T618C mutation described here is the second found in
this region. Both mutations affect the same base pair of the tRNA(Phe) anticodon
stem substantiating the pathogenic nature of both mutations.
PMID- 9636665
TI - Molecular cloning of multiple isoforms of synaptojanin 2 and assignment of the
gene to mouse chromosome 17A2-3.1.
AB - Synaptojanin 2 is an inositol polyphosphate 5'-phosphatase that appears to be
regulated by alternative splicing. By screening mouse cDNA libraries derived from
either mouse day 16 embryo or adult liver, we have identified additional
synaptojanin 2 cDNAs that represent six new isoforms of the protein. This
finding, together with other reports, indicates the presence of eight isoforms of
synaptojanin 2. Sequence analysis of our cDNA clones suggests that there are at
least two putative initiation sites and at least six different sequences coding
for the carboxyl-terminus of the molecule. In addition, we have mapped
synaptojanin 2 to mouse chromosome 17 band A2-3.1 by fluorescence in situ
hybridization.
PMID- 9636666
TI - Atrial natriuretic factor-induced amylase output in the rat parotid gland appears
to be mediated by the inositol phosphate pathway.
AB - In previous in vivo studies we have reported that atrial natriuretic factor
enhanced induced salivary secretion and increased isoproterenol-induced amylase
release in the rat suggesting that, ANF effect could be mediated by
phosphatidylinositol hydrolysis. In the present work, the effect of ANF on rat
parotid tissue incubated in vitro was investigated with the aim to assess whether
the phosphoinositol pathway was involved in ANF intracellular signaling in the
parotid gland. Results showed that ANF induced a dose dependent increase in
amylase fractional release, which was lower than that evoked by any concentration
of isoproterenol. Furthermore 100 nM ANF enhanced isoproterenol-evoked amylase
release. The effect of ANF was not affected in the presence of propranolol
suggesting the noninvolvement of the beta adrenergic receptor, which is the main
stimulus for the output of the enzyme in the parotid gland. However, ANF
increased phosphatidylinositol hydrolysis, which implies an increase in
intracellular calcium, which is necessary for the achievement of maximal response
in amylase release. This effect was abolished in the presence of neomycin
supporting ANF direct stimulation of phospholipase C. These results suggest the
involvement of the C type natriuretic peptide receptor coupled to phospholipase C
in ANF evoked amylase release and ANF enhancement of the isoproterenol-induced
output of the enzyme.
PMID- 9636667
TI - Novel carbazole degradation genes of Sphingomonas CB3: sequence analysis,
transcription, and molecular ecology.
AB - The degradation of aromatic compounds by bacteria is dependent upon specific
catabolic operons. The unique car locus isolated from Sphingomonas CB3 encodes
the first four enzymes involved in the catabolism of the azaarene carbazole.
These include a class II three-component dioxygenase enzyme system, a dihydrodiol
dehydrogenase, an extradiol (meta-cleavage) dioxygenase, and a hydrolase.
Homology of deduced amino acid sequences is closer to corresponding biphenyl
catabolic genes than to previously characterised carbazole degradation genes.
Gene arrangement is also identical to that found in some bph loci. The car genes
are transcribed when carbazole is utilised as a sole carbon source, and although
biphenyl does not serve as a growth substrate for Sphingomonas CB3 it is able to
act as a non-metabolisable inducer of the car locus. Ecologically the car genes
were detected in polycyclic aromatic hydrocarbon (PAH) contaminated soil
associated with a former town gas site.
PMID- 9636668
TI - Characterization of trypsin-modified bovine lens acylpeptide hydrolase.
AB - Acylpeptide hydrolase, which removes the N-acetylated amino acids from peptide
substrates was purified from bovine lens, truncated in vitro to a 55 kDa enzyme
by trypsin digestion and characterized. The activity of the trypsin-modified
enzyme was investigated using alpha A-crystallin and oxidized insulin A chain.
The trypsin-modified enzyme was able to unblock alpha A-crystallin and displayed
endoprotease activity unlike the native enzyme. SDS-PAGE analysis and amino acid
sequencing of (3H)iPr2P-F labeled bovine lens acylpeptide hydrolase showed that
the lens has a 55 kDa truncated form of the enzyme. The in vivo truncated form of
the enzyme was generated by the cleavage of the Gly203-Asp204 peptide bond in the
native enzyme.
PMID- 9636669
TI - Identification of the catalytic triad of the protein D2 protease in Pseudomonas
aeruginosa.
AB - We reported recently that protein D2 (OprD) porin of Pseudomonas aeruginosa bears
protease activity (FEBS Letters 394, 179-182, 1996). To identify the catalytic
residues of OprD, we introduced the site-directed mutations replacing the
putative catalytic triad His156, Asp208, and Ser296 with glutamine, asparagine,
and alanine, respectively. The OprD proteins purified from the chromosomal oprD
deficient mutants harboring the plasmids encoding the site-directed mutations
showed protease activity less than 0.1% of that of the wild-type OprD. These site
directed mutageneses caused undetectable changes in the pore-forming activity of
OprD as measured by single-channel conductance by the planar lipid bilayer. The
minimum inhibitory concentration of imipenem in mutants having the replaced
catalytic triads was identical with that in the wild-type strain. On the other
hand, introduction of the mutation at His367 replacing with glutamine, the site
that is supposed to be unrelated to the catalytic sites, showed the unchanged
protease activity. These results unequivocally demonstrate that OprD is the
protease bearing porin and catalyzes the reaction at His156, Asp208, and Ser296
residues.
PMID- 9636670
TI - Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18
and mutational analysis in breast cancer.
AB - The cyclin-dependent kinase (CDK) inhibitor p18 blocks progression of the cell
cycle by associating with the cyclin D-dependent kinases CDK6 and CDK4. To better
understand the regulation of p18 gene expression, we isolated full-length cDNA
clones from a human BT-20 breast cancer cell cDNA library. These clones were then
used to isolate the human gene from a human genomic DNA library. The human p18
gene spans at least 7.5 kb and is composed of three exons, two of which encode
the p18 protein. The genomic clone we isolated contained 5 kb of putative
promotor sequence which directed expression of the luciferase reporter gene in
transient transfection experiments. The longest cDNA that we isolated from BT-20
cells contained 2103 nucleotides which corresponds to the size of the major RNA
transcript detected by Northern analysis in these cells. Transcription start
sites mapping to the 5' end of the putative full-length cDNA were identified by
ribonuclease protection assays. A novel polymorphism was identified in the 3'
untranslated region of BT-20 cell cDNA clones that contained the previously
described codon 72 mutation. The codon 72 mutation was also detected in 3 of 35
breast tumors analyzed using a mismatch PCR/RFLP strategy.
PMID- 9636671
TI - Ocular lens NAD kinase: partial purification and metabolic implications.
AB - The ocular lens displays a significant amount of NADP(H) dependent metabolic
traffic, but the origin of this cofactor has not been established. Size exclusion
chromatography of bovine lens crude extract on a Sephacryl S300-HR column fitted
with an eluate concentrator revealed two bands with NAD kinase activity, based on
enzymatic cycling with signal amplification of the column fractions using a Cobas
Fara II centrifugal fast analyzer. Ve/Vo ratios from the chromatographic runs
suggest that the relative molecular weight values lie within the ranges 8.91-3.98
x 10(5) and 2.04-1.26 x 10(5), respectively, for these two bands. An
approximately 10-fold enhancement of enzyme activity over the crude fraction is
realized from the chromatography step. Results point to NAD kinase as the source
generator of this anchoring and linking cofactor for the oxidative stress and
pentose phosphate enzyme systems, respectively.
PMID- 9636672
TI - Iron compounds after erythrophagocytosis: chemical characterization and
immunomodulatory effects.
AB - In humans, the lymphomyeloid system has a fundamental role on iron metabolism
promoting its recycling due to a continuous removal of effete red blood cells.
Additionally, one of the most intriguing aspects of metalloporphyrins in biology
is their effect on the immune system. However, the process of erythrocyte
catabolism is still poorly understood and needs further research. In the present
study, we attempt to investigate the nature and the possible physiologic role of
Fe compounds released after erythrophagocytosis during the removal of red blood
cells. Monocyte erythrophagocytosis in vitro experiments were done to
characterize chemically the Fe compounds present inside the cells and in the
culture supernatants. We tested the probable immunomodulatory functions of
erythrophagocytosis products over lymphocyte cultures activated in vitro with T
mitogens (alpha-CD3). Data obtained from atomic absorption spectroscopy confirmed
the presence of Fe in the culture supernatants of monocyte cultures after
erythrophagocytosis. Also, high-spin haem complexes derived from erythrocyte
catabolism were detected by electron paramagnetic electronic resonance. Finally,
in vitro activated lymphocyte proliferation experiments indicate the co-mitogenic
properties of monocyte culture supernatants after red blood cells phagocytosis.
Thus, the results of the present work provide evidence that culture monocyte
supernatants after in vitro erythrophagocytosis contain Fe (III) high-spin haem
complexes and show lymphocyte proliferation co-stimulatory properties.
PMID- 9636673
TI - Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by
plasma antioxidants.
AB - We have applied our method for the simultaneous detection of plasma ubiquinol-10
(reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto,
Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and
patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and
hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in
these patients. The average ubiquinone-10 percentages (+/- S.D.) in total
ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/-
10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant
increase in ubiquinone-10 percentage in patient groups in comparison to normal
subjects. These results and a significant decrease in the plasma ascorbate level
in patient groups indicate that oxidative stress is evident after the onset of
hepatitis and the subsequent cirrhosis and liver cancer.
PMID- 9636674
TI - APS kinase from Arabidopsis thaliana: genomic organization, expression, and
kinetic analysis of the recombinant enzyme.
AB - The gene encoding 5'-adenylylsulfate (APS) kinase (EC 2.7.1.25) (APK) was cloned
from Arabidopsis thaliana. There is a single APK locus in A. thaliana. The coding
sequence of the gene is composed of 7 exons, interrupted by 6 introns. A
transcriptional initiation site was detected 120 bp 5' of the initiation codon.
APK mRNA is slightly more abundant in leaves than in roots of A. thaliana and its
level does not change in response to sulfur starvation. The APK protein,
synthesized in vitro, is able to enter isolated intact chloroplasts. Recombinant
APS kinase shows maximal activity at 10 microM APS with 5 mM ATP, but it is
inhibited at APS concentrations above 10 microM. The inhibition is alleviated at
higher ATP concentrations. Reciprocal plot analysis showed that the theoretical
Vmax is approximately 1.2 mumol min-1 mg-1 at 25 degrees C, pH 8.0; the K(m)
values are 3.6 microM APS and 1.8 mM ATP.
PMID- 9636675
TI - In vitro inhibition of Ras-Raf association by short peptides.
AB - Seven amino acid peptides were tested as in vitro inhibitors of oncogenic Ras-Raf
association. The sequences of these peptides were derived from the H-Ras effector
region (amino acids 25 to 51) and the Ras binding domain of Raf-1 (amino acids 64
to 105). Eleven out of the twenty-one Ras 7-mers tested inhibited formation of
the Ras-Raf complex by at least 20% at 100 microM. The most potent of these
inhibitory peptides contained the effector residues 32 to 37 or 40 to 45. Of the
Raf-1 peptides tested, only the 94-ECCAVFR-100 and 95-CCAVFRL-101 peptides were
significant inhibitors of Ras-Raf binding. The 95-101 Raf peptide had an IC50
value of 7 microM and also inhibited Ras-RalGDS binding. Analysis of the 95-101
peptide showed that its inhibitory activity required at least one cysteine
followed by several hydrophobic residues. Our results demonstrate the feasibility
of using small molecules as inhibitors of Ras protein-protein interactions.
PMID- 9636676
TI - Chiral inversion of 1-hydroxyethylpyrene enantiomers mediated by enantioselective
sulfotransferases.
AB - The benzylic alcohol 1-hydroxyethylpyrene (1-HEP) is activated to a mutagen by
sulfotransferases. The sulfuric acid ester formed is difficult to detect, as it
is rapidly hydrolysed back to the alcohol. Incubation of the individual
enantiomers of 1-HEP with human hydroxysteroid sulfotransferase (hHST) or
estrogen sulfotransferase (hEST), expressed in bacteria, led to the formation of
the other enantiomer. The rates of sulfation were determined from the initial
rates of chiral inversion of the alcohol, knowing that hydrolysis follows an SN1
mechanism and therefore produces racemic alcohol. hEST showed high
enantioselectivity for S-1-HEP, whereas hHST strongly preferred the R-enantiomer.
The rates of sulfation of the preferred enantiomers were high, similar to those
for the prototype substrates of hEST (beta-estradiol) and hHST
(dehydroepiandrosterone). Moreover, after a 30-min incubation of S-1-HEP with
hEST, 95% of the recovered alcohol showed the R-configuration, indicating that
several cycles of sulfation and hydrolysis had led to the depletion of one
enantiomer and to the enrichment of the other enantiomer.
PMID- 9636677
TI - Effect of laminin on the nuclear localization of nucleolin in rat intestinal
epithelial IEC-6 cells.
AB - Laminin is a major component of extracellular matrix. The mechanism of action of
laminin on cell proliferation, differentiation, and migration is not fully
understood. In this study, we investigated the role of extracellular matrix,
especially laminin, on the cellular localization of the nuclear protein,
nucleolin, and on cell proliferation. Immunofluorescent and western blot analysis
indicated that nucleolin was translocated most efficiently to the nucleus in the
small intestinal rat epithelial cell line (IEC-6) when cultured on laminin-coated
plates. Specifically, nucleolin was observed predominantly in cytoplasm in the
cells cultured without laminin. In contrast, nuclear localization was observed in
the cells cultured on laminin. This effect of laminin on nucleolin translocation
was time-dependent. Laminin was also observed to stimulate proliferation of IEC-6
cells in serum free medium. Our results suggest that laminin alters the
distribution of nucleolin which may be an early signal for cell proliferation.
PMID- 9636678
TI - Differentiation of forbidden T cell clones and granulocytes in the parenchymal
space of the liver in mice treated with estrogen.
AB - Estrogen was administered to B6 (NK1.1+ strain), BALB/c (Mls-1b2a, V beta 3+
cells being forbidden clone), or (B6 x BALB/c) F1 mice (1 mg/mouse). On days 3
and 10, the number of cells yielded by the liver doubled, whereas that yielded by
the thymus decreased prominently. The numbers of cells in the spleen, bone
marrow, and blood were unchanged. c-kit+ stem cells, which give rise to
multilineage cells, were present in the liver and bone marrow. The proportion of
such c-kit+ cells in the liver increased while that in the bone marrow decreased
on day 3. Therefore, the absolute number of c-kit+ stem cells increased
severalfold in the liver and clusters of lymphoid cells became visible in the
parenchymal space. At that time, the expression of recombination activating gene
1 and -2 mRNAs became prominent. Reflecting these phenomena, the number and
proportion of IL-2R beta+ CD3int cells (i.e., primordial T cells) increased in
the liver on days 3 and 10. An increase in the number of proportion of such
CD3int cells was seen even in the thymus and uterus. In parallel with the
increase of CD3int cells, the proportion of granulocytes also increased in
various organs on day 3. Forbidden clones were present in either the NK1.1+ or
the NK1.1- subset of CD3int cells in (B6 x BALB/c) F1 mice treated with estrogen
and liver mononuclear cells in such mice acquired potent cytotoxicity against
syngeneic thymocytes. These results reveal that estrogen has the ability to
potentiate the generation of self-reactive T cells and granulocytes in the liver
and other organs.
PMID- 9636679
TI - Intermediate TCR cells can induce graft-versus-host disease after allogeneic bone
marrow transplantation.
AB - Mice fall victim to GVHD when subjected to immunosuppressive treatment and
injected with allogeneic bone marrow cells. A major population of cells
associated with GVHD is known to be T cells. However, whether such T cells are of
thymic or extrathymic origin is obscure. We applied two immunosuppressive
conditions, 9 and 6.5 Gy irradiation, to C3H/He mice (H-2k). Bone marrow cells
for injection were obtained from C57BL/6 (B6) mice (H-2b). The 9-Gy mice were
reconstituted by lymphocytes of donor origin and showed GVHD, whereas 6.5-Gy mice
were reconstituted by lymphocytes of recipient origin and showed mild GVHD. The
liver was the organ where the reconstitution of lymphocytes occurred efficiently,
and a major lymphocyte subset was intermediate (int) CD3 cells (i.e., CD3int
cells) in both mice. CD3int cells had the properties of extrathymic T cells,
showing the phenotype of NK1.1 + CD3int using invariant V alpha 14 chain. In 6.5
Gy mice, allogeneic cells were rejected by extrathymic T cells of recipient
origin. The stored CD3int cells from the liver of 9-Gy mice evoked similar GVHD
when transferred into 6.5-Gy irradiated C3H/He mice. These results suggest that
CD3int cells of extrathymic origin are a major population for the induction of
GVHD under immunosuppressive conditions.
PMID- 9636680
TI - Internalization of iscom-borne antigens and presentation under MHC class I or
class II restriction.
AB - Exogenous nonreplicating antigens (Ag) incorporated into immunostimulating
complexes (iscoms) induce CTL responses under MHC class I restriction. A
requirement for inducing CTL responses is that the Ag is delivered to the cytosol
of antigen-presenting cells (APC), a route restricted to endogenously produced
Ag. To investigate the mechanisms by which iscoms elicit MHC class I-restricted
responses, the intracellular distribution of influenza virus envelope proteins
incorporated in iscoms (flu-iscoms) or in micelles (flumicelles) was studied in
vitro using murine peritoneal cells (PEC). Ultrathin sections of cells pulsed
with biotinylated flu-iscoms or flu-micelles were analyzed by electron microscopy
after detection of the biotin label by reaction with streptavidin-gold. PEC
pulsed with flu-iscoms showed a pattern of scattered gold particles distributed
in clear and dense vesicles as well as in the intracellular space but not
associated with organelles. In cells pulsed with flu-micelles, Ag was also
detected in most cellular compartments but at a considerably lower concentration.
The intracellular distribution of particulate Ag in iscom or micelle form was
confirmed by lysis and differential centrifugation of Ag-pulsed APC. Furthermore,
P815 cells pulsed with flu-iscoms were lysed by specific immune effectors showing
that the iscom-Ag was processed and presented by class I-expressing APC. Flu
iscoms were internalized about 50-fold more efficiently than ovalbumin iscoms
(ovaiscoms) suggesting that the nature of the protein and/or the presence of
cellular receptors are important factors influencing the capacity of APC to take
up iscom-borne proteins. PEC accounted for the most active internalization of
iscom-borne Ag, although splenic dendritic cells and B cells also took up
fluiscoms with remarkable efficiency.
PMID- 9636681
TI - Activation of p21ras/MAPK signal transduction molecules decreases with age in
mitogen-stimulated T cells from rats.
AB - Signal transduction is ubiquitously involved in the initiation of physiological
signals that lead to growth and proliferation of cells. The signaling cascade
mediated by the mitogen-activated protein kinase (MAPK) is considered essential
for T cell growth and function. Therefore, it was of interest to determine the
influence of age on the induction of MAPK in mitogen-activated T cells. T cells
from young (4-6 months) and old (24-26 months) rats responded to concanavalin A
(Con A) stimulation by increasing MAPK, c-jun amino terminal kinase (JNK), and
p21ras activities. The time course of induction of MAPK/JNK and p21ras activities
was similar in T cells isolated from young and old rats. The induction of JNK
activity did not change significantly with age; however, the induction of MAPK
and p21ras activities was significantly less (50 to 65%) in T cells from old rats
than in T cells from young rats. Although the relative protein levels of p42 and
p44 MAPK did not change with age, the proportion of the phosphorylated p44 MAPK
decreased with age. In addition, it was found that the in vitro kinase activities
of the T cell receptor-associated protein tyrosine kinase Lck (p56Lck) and ZAP-70
but not Fyn (p59Fyn) were lower in T cells from old rats than in T cells from
young rats. The decline in activities of these signaling molecules with age was
not associated with changes in their corresponding protein levels. Thus, our
results demonstrate that aging alters the activation of the signal transduction
cascade that leads to T cell activation.
PMID- 9636682
TI - Functional consequences of the SHP-1 defect in motheaten viable mice: role of NF
kappa B.
AB - To define the functional consequences of the src-homology domain-1 protein (SHP
1) defect, we examined cytokine production and NF-kappa B activity in motheaten
viable (Mev) mice. We found elevated levels of interleukin-6 (IL-6), interleukin
10 (IL-10), tumor necrosis factor (TNF), and interferon-gamma (IFN-gamma) in Mev
mice sera and cultured B and T cells compared to littermate control adult mice.
The levels of interleukin-2 (IL-2) detected in Mev sera and activated Mev T cells
were decreased, but IL-2 receptor expression was increased. We then evaluated the
activity of NF-kappa B and found that this protein is highly expressed in Mev B
and T cells. To determine if NF-kappa B had a role in causing the elevated levels
of cytokines in Mev mice, we treated activated Mev T cells with an NF-kappa B
decoy and found that cell culture treatment with the decoy resulted in
significant reduction of the secretion of IL-6, GM-CSF, and TNF, but not IFN
gamma. Therefore, our data show that Mev mice secrete elevated levels of
inflammatory cytokines, which can be mediators in the development of the Mev
clinical disorder, and that NF-kappa B has an important role in this process,
impacting upon the regulation of the immune response.
PMID- 9636683
TI - Cytokine release by macrophages after interacting with CSF-1 and extracellular
matrix proteins: characteristics of a mouse model of inflammatory responses in
vitro.
AB - Extracellular matrix (ECM) proteins play a key role at sites of inflammation
where they regulate the inflammatory properties of infiltrating leukocytes.
Previous data indicated that the macrophage colony-stimulating factor (CSF-1 or M
CSF) primed subpopulations of mononuclear phagocytes (MNP) for differential
inflammatory responses and rendered defined populations extremely sensitive to
secondary stimulation as measured by cytokine gene expression. In this report, we
focus on the question whether CSF-1 modified the inflammatory responsiveness of
elicited peritoneal macrophages (PM phi), as a defined subpopulation of MNP, to
secondary stimulation by ECM proteins as a component of inflammatory lesions. It
was seen that CSF-1-primed PM phi responded to fibronectin (FN) and collagen type
IV (COL IV) in vitro by releasing large amounts of IL-6 but released only minimal
quantities when exposed to vitronectin (VN) or to untreated plastic surfaces. TNF
alpha and GM-CSF proteins were not released. Preincubation of the PM phi with CSF
1 or 10% FBS for up to 12 h prior to exposure to ECM proteins was shown to
further enhance the release of IL-6 when the cells were cultured with FN but to
result in a loss of secretory activity when placed on COL IV. In addition,
preincubated PM phi in contact with FN were shown to release TNF-alpha but not GM
CSF. CSF-1 did not enhance VLA 4 (alpha 4 beta 1 or CD49d) but enhanced VLA 5
(alpha 5 beta 1 or CD49e) expression. However, blocking with either anti-VLA 4 or
VLA 5 monoclonal antibodies inhibited the IL-6 response. These data suggest that
CSF-1 primes elicited PM phi for differential expression of adhesion molecules
that are required for binding to individual ECM proteins and for modulating
inflammatory responses of MNP.
PMID- 9636684
TI - Vaccination with dendritic cells inhibits the growth of hepatic metastases in B6
mice.
AB - Dendritic cells (DC) are specialized antigen-presenting cells that can activate
naive and mature T-cells, induce cellular immunity, and stimulate strong
antitumor reactions in vivo. This study was undertaken to examine the function of
DC vaccines in suppressing the growth of hepatic metastases in C57BL/6 mice.
Experimental mice received two i.v. doses of 1 x 10(6) bone marrow-derived DC,
either unpulsed or pulsed with MCA-106 fibrosarcoma cell lysates, on days -14 and
-7. Controls were injected with HBSS. Hepatic metastases were established on day
0 through intrasplenic injections of 1 x 10(5) MCA-106 tumor cells. Animals were
sacrificed on day 21 and their livers were excised to assess tumor burden.
Splenocytes from DC-treated groups were cytotoxic against MCA-106 cells, but not
against the L929 and CT26 (syngeneic fibroblast and colon tumor, respectively)
cell lines. All control mice developed grossly evident hepatic metastases, while
62 and 44% of the mice receiving MCA-106 cell lysate-pulsed DC and unpulsed DC
vaccines, respectively, were completely free of tumor. Mean hepatic mass for the
controls, including tumor, was almost double that for treated animals. Antibody
depletion of either CD4+ or CD8+ lymphocytes abrogated the protective effect of
the vaccine. This study demonstrates that immunization with DC confers cellular
immunity, with both CD4+ and CD8+ T-cells playing a significant role, and impedes
the subsequent establishment and growth of hepatic metastases in mice. The
antitumor capabilities of DC justify their use in immunotherapeutic vaccines
against human cancers.
PMID- 9636685
TI - Vitamin A inhibits cytokines produced by type 1 lymphocytes in vitro.
AB - The effect of vitamin A (retinol) on cell-mediated immune responses was studied.
As an experimental model, Leishmania major infection in mice was used. In this
model, resistant mouse strains develop a type 1 response, while susceptible
strains develop a type 2 response. Using lymph node cells and T-cell lines
developed from infected susceptible and resistant mice, it was found that vitamin
A inhibited lymphocyte proliferation in a dose-dependent manner. By separately
incubating antigen-presenting cells and T cells with vitamin A, it was shown that
the inhibitory effect was on the T cells. Type 1 cytokine (IFN-gamma, GM-CSF, IL
2) secretion in vitro in response to stimulation with specific antigen was also
inhibited in a dose-dependent manner, whereas secretion of type 2 cytokines (IL-4
and IL-10) was not affected by vitamin A. The inhibitory effect was also observed
in PMA-stimulated (but not Con A-stimulated) lymphocytes and was noticeable even
if the vitamin was added as late as 24 h after initiation of the incubation
period. Since PMA does not operate via a receptor-coupled signaling pathway but
rather directly affects the protein kinase C (PKC) pathway, we have measured the
effect of vitamin A on PKC in situ activation. Incubation of lymphocytes and
antigen in the presence of vitamin A caused inhibition of PKC isoenzymes
translocation to the particulate cell fraction, as measured by immunoblotting.
The results presented indicate that, when added to cell cultures in vitro,
vitamin A inhibits only secretion of type 1 but not type 2 cytokines, possibly
through an inhibitory effect on protein kinase C activity.
PMID- 9636686
TI - Interleukin (IL)-15 enhances antibody-dependent cellular cytotoxicity and natural
killer activity in neonatal cells.
AB - Interleukin (IL)-15 is a novel cytokine that is very similar to IL-2 in receptor
specificity and biological activities. We compared the ability of IL-15 and IL-12
to enhance the cytotoxicity of neonatal (cord blood) and adult mononuclear cells
(MNC) in both natural killer (NK) and antibody-dependent cellular cytotoxicity
(ADCC) assays. Incubation with IL-15 (10 ng/ml) or IL-12 (1 ng/ml) for 18 h
enhanced the NK activity (using K562 target cells) of both cord and adult MNC,
increasing cord cell cytotoxicity threefold. Similar enhancement was seen in ADCC
assays using erythrocyte targets and NK-resistant CEM cells coated with HIV gp
120 antigen. Incubation of cord cells with IL-15 or IL-12 for 1 week increased
both NK and ADCC, although the combination produced less of an effect than either
cytokine alone. IL-15 also increased the percentage of CD16+/CD56+ cells after 1
week incubation. This enhancement of NK and ADCC activities and the number of NK
cells by IL-15 suggests it may be clinically useful in treating immunodeficient
patients.
PMID- 9636687
TI - B-cell superantigens may play a role in B-cell development and selection in the
young rabbit appendix.
AB - In order to develop protective antibodies against a wide range of potentially
infectious pathogens, the young rabbit must diversify a limited initial
repertoire by somatic mechanisms (the high copy number primary repertoire). The
majority of rabbit B cells produce heavy chain variable regions by rearranging
the VHa allotype-encoding VH1 gene. Thus in normal rabbits the majority of serum
immunoglobulins bear VHa allotype (due to VH1 FR1 and FR3 sequences). The young
rabbit appendix is a site of diversification of rearranged VH genes by gene
conversion-like and somatic hypermutation mechanisms. The newly generated B cells
probably undergo selection processes that involve foreign and self-antigens and
superantigens. We find preferential expansion and survival of B cells in normal
and VH-mutant ali/ali rabbits based on their heavy chain FR1 and FR3 sequences
(VHa allotype). This selection may involve "superantigen"-like interactions with
endogenous as well as exogenous ligands.
PMID- 9636689
TI - An anergic cytotoxic T lymphocyte clone exhibits granule exocytosis-mediated
cytotoxicity.
AB - T cell receptor (TCR) occupancy in the absence of a costimulatory signal
transforms T helper (Th) cells or cytotoxic T lymphocytes (CTL) into a state of
anergy. The anergic T cells are unable to produce cytokines; nevertheless, they
maintain their killing activity. We investigated the mechanisms through which
anergic CTL causes lysis of target cells. Treatment of a CTL clone with phorbol
myristate acetate and calcium ionophore A23187 (P/A) transformed these cells to
anergic cells. While the anergic CTL clones failed to secrete TNF-alpha in the
culture supernatant, they were still able to kill antigen-specific target cells
via a granule exocytosis-mediated pathway. This was evident by the synthesis of
perforin mRNA and release of N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester
esterase by these cells. The anergic CTL clone also showed a low degree of Fas
mediated lysis of normal target cells. In addition, we generated anergic bulk CTL
by treatment with P/A and observed that the anergic bulk CTL failed to produce
TNF upon antigen stimulation, but retained target killing activity via a granule
exocytosis mechanism. Our results suggest that the killing mechanisms of anergic
CTL are mediated to a large extent by a granule exocytosis-mediated pathway.
PMID- 9636688
TI - A humanised therapeutic CD4 mAb inhibits TCR-induced IL-2, IL-4, and IL-10
secretion and expression of CD25, CD40L, and CD69.
AB - The actions of a humanised therapeutic CD4 mAb YHB.46 on T cell activation were
investigated in vitro. Soluble YHB.46 IgG or YHB.46-derived F(ab')2 fragments
caused inhibitions of up to 100% of the proliferation of purified CD4+ T cells
activated with immobilised CD3 mAb. The inhibitory effects of the CD4 mAb were
equally potent in both CD45RA+ and CD45RO+ T cell subset proliferation assays.
Inhibitory effects on DNA synthesis were nto explicable by increased T cell
apoptosis. YHB.46 was inhibitory even when added 70 h after exposure of cells to
immobilised CD3 mAb, but it had little effect on IL-2 receptor-driven
proliferation signals. The CD4 mAb inhibited the CD3-induced expression of the
CD25 and CD69 activation markers on the T cell surface and suppressed CD40 ligand
expression, but not that of CD25 and CD69, when their expression was induced by
phorbol ester plus ionomycin. YHB.46 also exerted a profound inhibitory effect on
the production of IL-2, IL-4, and IL-10, irrespective of whether T cells were
activated with CD3 mAb or with phorbol ester plus ionomycin. The inhibitory
effects of YHB.46 on CD4+ T cell proliferation were partially prevented by the
addition of exogenous IL-2 or autologous monocytes and were completely prevented
by activating T cells with a novel CD3-CD28 bivalent F(ab')2 reagent. However,
the inhibitory effects of YHB.46 on T cell proliferation were equipotent in the
presence or the absence of CTLA-4Ig, showing that the CD4 mAb was not acting on
CD28-induced activation signals per se. Our results show that the inhibitory
effects of YHB.46 on T cell activation do not involve CD28 or IL-2 receptor
signalling, but are directed at the TCR-mediated G0-G1 transition. These findings
in vitro predict that YHB.46 may act as a potent immunosuppressant in the
clinical context.
PMID- 9636690
TI - A thymic nurse cell-specific monoclonal antibody.
AB - A thymic epithelial cell line (tsTNC-1) that maintains the ability to selectively
bind and internalize immature alpha beta TCRloCD4+CD8+ thymocytes in vitro was
used in the development of a monoclonal antibody that is specific to the cell
surface of thymic nurse cells (TNCs) in the thymus. The rat monoclonal antibody
ph91 showed specificity to cells of the subcapsular region of the thymic cortex.
Upon mechanical dispersion of the thymus in vitro, ph91 recognized cells
displaying the multicellular morphology unique to TNCs. Ph91 staining was not
detected on fresh thymocytes, stromal cells of the inner thymic cortex, thymic
medullary cells, B cells or fibroblasts. Ph91 recognized a 43-kDa protein on the
surface of TNCs. Exposure of tsTNC-1 cells to ph91 in tissue culture
significantly reduced the percentage of binding of the alpha beta TCRloCD4+CD8+
thymocyte subset previously shown to target TNCs. In organ culture, ph91 reduced
the viability of developing thymocytes by 70%. The largest reduction was found in
the alpha beta TCR+CD4+CD8+ thymocyte subset. These results represent the first
report of a TNC-specific monoclonal antibody. Further, the antigen to which ph91
binds may play a role in the process of thymocyte binding and their subsequent
internalization which is unique to TNCs and important to the T cell developmental
process.
PMID- 9636691
TI - In vitro thymocyte maturation is associated with reduced cellular susceptibility
to Fas-mediated apoptosis.
AB - We have developed a novel system in which the susceptibility of murine thymocytes
to Fas-mediated apoptosis can be modulated. Thymocyte susceptibility to Fas
decreases under in vitro culture conditions that promote aspects of thymocyte
maturation. The hyporesponsive state is specific for the Fas pathway, since
cellular susceptibility to other apoptotic stimuli is not reduced.
Hyporesponsiveness is not associated with alterations in the thymocyte subset
distribution, decreased expression of full-length Fas protein, or alterations in
FADD, Bcl-2, or Bcl-XL expression. Hyporesponsiveness is overcome by increasing
the strength of the Fas cross-linking stimulus, leading us to propose that
reduced thymocyte susceptibility to apoptosis results from altered Fas signaling.
The block in Fas signaling resides proximal to ceramide generation, since Fas
hyporesponsive thymocytes are susceptible to ceramide-induced apoptosis. Further
characterization of Fas signaling in these in vitro cultured thymocytes may
facilitate the identification of factors regulating the susceptibility of wild
type lymphocytes to Fas.
PMID- 9636692
TI - Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial
lipopolysaccharide that acts in synergy with c-kit ligand and Fc epsilon receptor
I crosslinking in cultured mast cells.
AB - Emerging evidence has suggested the pivotal role of mast cells in a host defense
against bacterial infection. In this paper, we report that bacterial
lipopolysaccharide (LPS) is a potent enhancer of the cytokine- and IgE-dependent
delayed responses of IL-3-dependent mouse bone marrow-derived cultured mast cells
(BMMC). LPS, although showing minimal effects, significantly augmented the c-kit
ligand (KL)- or IgE-dependent expression of cyclooxygenase (COX)-2 and the
attendant delayed PGD2 generation, with IL-10 and IL-4 acting as potentiating and
inhibitory cytokines, respectively. The COX-2-inducing activity of LPS was
mimicked by exogenous IL-1 beta. Assessment of endogenous cytokine induction
revealed that IL-1 beta expression was stimulated by either LPS or exogenous IL-1
beta. IL-6 expression occurred in parallel with COX-2 expression. IL-10
expression, which lagged behind COX-2 expression, depended on exogenous IL-10,
but not on LPS and IL-1 beta. Thus, LPS and IL-1 beta exhibited similar
biological activities in terms of COX-2 and endogenous cytokine expression.
However, adding an antibody against the type I IL-1 receptor to BMMC, which
abrogated the effects of IL-1 beta, failed to neutralize the effects of LPS.
These results suggest that LPS activates BMMC through the signal transduction
pathway shared with exogenous IL-1 beta, rather than exerting its action
indirectly via the production of endogenous IL-1 beta.
PMID- 9636693
TI - Enhancement of T-cell-mediated arthritis in mice by treatment with a monoclonal
antibody against interleukin-4.
AB - We investigated a role for interleukin-4 (IL-4) in T-cell-mediated arthritis by
employing a monoclonal antibody against IL-4 (11B11 mAb). As a model of T-cell
mediated arthritis, antigen-induced arthritis (AIA) in mice was used. To induce
AIA, mice were immunized with methylated bovine serum albumin (mBSA) (day 0). On
day 14, the animals were intraarticularly injected with mBSA into the ankle
joint. 11B11 mAb was daily injected i.p. for a period of 10 days, commencing on
the day of immunization with mBSA. We found that treatment with 11B11 mAb
significantly enhanced the severity of AIA. The enhanced arthritis was also
observed in mice injected i.v. with lymphoid cells from mBSA-immunized mice,
followed by the intraarticular challenge injection of mBSA. The enhancement of
AIA by the anti-IL-4 mAb was associated with a significant increase in the
proliferative response of lymphoid cells to mBSA in mice treated with the mAb.
The secretion of IL-4 as well as IL-5 decreased in 11B11 mAb-treated mice, while
the production of IFN-gamma and IL-2 increased following mAb treatment. Thus, the
neutralization of IL-4 by an anti-IL-4 mAb appeared to enhance AIA, suggesting a
role for IL-4 in downregulating T-cell-mediated joint inflammation.
PMID- 9636694
TI - Lymphokine regulation of activation-induced apoptosis in T cells of IL-2 and IL
2R beta knockout mice.
AB - Recent studies using IL-2R alpha knockout mice have generated conflicting results
regarding the hypothesis that IL-2/IL-2R interaction is obligatory for the
development of AICD, which plays a central and pivotal role in maintaining
peripheral tolerance. A relevant consequence of AICD defect is the demonstrated
development of autoimmune lymphoproliferative disease in IL-2, IL-2R alpha, and
IL-2R beta knockout mice, but not in IL-4, IL-7, or IL-7R knockout mice. Whether
IL-4, IL-7, or IL-15 can provide the required signal for AICD development is
addressed here using IL-2 and IL-2R beta knockout mice. Lymph node T cells from
knockout mice were stimulated with Con A plus rIL-1 for 3 days and then
maintained in high concentrations of rIL-4, rIL-7, or rIL-15 for an additional 3
days before they were subjected to AICD analysis. Our study demonstrates that IL
4, IL-7, and IL-15 can transduce signals critical for AICD development in the
absence of IL-2-mediated signals. The requirement for relatively high
concentrations of these lymphokines suggests their limited role in maintaining
peripheral T cell tolerance, thus explaining the differential expression of
autoimmune lymphoproliferative disease in the targeted mutant strains described
above.
PMID- 9636695
TI - A structural switch in a mutant insulin exposes key residues for receptor
binding.
AB - Despite years of effort to clarify the structural basis of insulin receptor
binding no clear consensus has emerged. It is generally believed that insulin
receptor binding is accompanied by some degree of conformational change in the
carboxy-terminal of the insulin B-chain. In particular, while most substitutions
for PheB24 lead to inactive species, glycine or D-amino acids are well tolerated
in this position. Here we assess the conformation change by solving the solution
structure of the biologically active (GluB16, GlyB24, desB30)-insulin mutant. The
structure in aqueous solution at pH 8 reveals a subtle, albeit well-defined
rearrangement of the C-terminal decapeptide involving a perturbation of the B20
23 turn, which allows the PheB25 residue to occupy the position normally taken up
by PheB24 in native insulin. The new protein surface exposed rationalizes the
receptor binding properties of a series of insulin analogs. We suggest that the
structural switch is forced by the structure of the underlying core of species
invariant residues and that an analogous rearrangement of the C-terminal of the B
chain occurs in native insulin on binding to its receptor.
PMID- 9636696
TI - Inhibition of Escherichia coli RNA polymerase by bacteriophage T4 AsiA.
AB - The 10 kDa bacteriophage T4 antisigma protein AsiA binds the Escherichia coli RNA
polymerase promoter specificity subunit, sigma 70, with high affinity and
inhibits its transcription activity. AsiA binds to sigma 70 primarily through an
interaction with sigma 70 conserved region 4.2, which has also been implicated in
sequence-specific recognition of the -35 consensus promoter element. Here we show
that AsiA forms a stable ternary complex with core RNA polymerase (RNAP) and
sigma 70 and thus does not inhibit sigma 70 activity by preventing its binding to
core RNAP. We investigated the effect of AsiA on open promoter complex formation
and abortive initiation at two -10/-35 type promoters and two "extended -10"
promoters. Our results indicate that the binding of AsiA to sigma 70 and the
interaction of sigma 70 region 4.2 with the -35 consensus promoter element of
10/-35 promoters is mutually exclusive. In contrast, AsiA has much less effect on
open promoter complex formation and abortive initiation from extended -10
promoters, which lack a -35 consensus element and do not require sigma 70
conserved region 4.2. From these results we conclude that T4 AsiA inhibits E.
coli RNAP sigma 70 holoenzyme transcription at -10/-35 promoters by interfering
with the required interaction between sigma 70 conserved region 4.2 and the -35
consensus promoter element.
PMID- 9636697
TI - The major coat protein of filamentous bacteriophage f1 specifically pairs in the
bacterial cytoplasmic membrane.
AB - Filamentous bacteriophage are long, thin single-stranded DNA viruses that infect
male strains of Escherichia coli without killing the host. Each phage contains
approximately 2700 copies of the major coat protein, pVIII, which exists as a 5.2
kDa cytoplasmic membrane protein prior to incorporation into phage. Studies from
a number of groups analyzing the behavior of wild-type and mutant pVIII in
detergents suggested that pVIII might pair under these conditions. In order to
test whether pVIII molecules pair in vivo in the cytoplasmic membrane, four
plasmidencoded pVIII variants were constructed in which specific residues in the
transmembrane region were mutated to cysteine in an attempt to stabilize any pair
via disulfide bridges. Variants A35C and I39C were unable to complement phage
with an amber mutation in gene VIII. The I39C variant was unable to be packaged
into phage particles even though it was inserted into the membrane. In the case
of A35C, the inability to complement was not due to a packaging defect because
the variant protein could be packaged into phage in the presence of wild-type
pVIII. Western blot analysis of cytoplasmic membrane samples revealed that the
A35C variant formed stable disulfide dimers in vivo. Expression of A35C
interfered with wild-type phage infection, indicating that the assembly machinery
may recognize the disulfide dimers in some non-productive way. The results
indicate that pVIII may specifically pair along a particular face in the
cytoplasmic membrane prior to assembly; however, these pairs must be able to be
separated in order for normal assembly to occur.
PMID- 9636698
TI - Mutations affecting cooperative DNA binding of phage HK022 CI repressor.
AB - Cooperative protein-DNA interactions play critical roles in gene regulation in
all organisms. Among the best-studied cooperative interactions is that of phage
lambda repressor, which binds cooperatively to two adjacent operators. Similar
cooperative interactions are also shown by several other lambdoid phage
repressors, including HK022 CI repressor, which we study here. This protein has a
much higher degree of cooperativity than seen with lambda repressor, and previous
evidence has suggested that cooperativity may play roles in HK022 gene regulation
that have no parallel in lambda. We have isolated several cooperativity or Coop-
mutations in HK022 cI. These mutant proteins were partially defective in vivo for
binding to two adjacent operators, but normal or nearly so for binding to a
single operator. Two mutations showed mutual suppression, in that the double
mutation had wild-type behavior. Analysis of several purified mutant proteins
showed that they were also defective for cooperative binding in vitro.
Unexpectedly, the mutant proteins showed an altered pattern of in vitro binding
to DNA at non-operator sites. Several of them also increased the rate of specific
repressor cleavage. We propose a conformational model in which the various
functions of the wild-type protein are carried out by differing conformations;
these conformations are normally in balance, and the mutations perturb this
balance.
PMID- 9636700
TI - Quantitative analysis of DNase I digestion patterns of oligo- and
polynucleosomes.
AB - DNase I digestion of unlabelled chromatin has been used to determine the
orientation of nucleosomes in the higher-order structure of chromatin. DNA
digestion patterns were analysed quantitatively and compared with simulation
curves that were generated with the experimentally obtained rate constants for
cutting inside nucleosomes and the half-height widths of the bands. The rate
constants for cutting at the linker DNA were varied to fit the experimental
curves. By comparing the digestion profiles of polynucleosomes, oligonucleosomes
and H1/H5-depleted oligonucleosomes we have been able to distinguish between
protection caused by H1/H5 histones only and protection caused by the higher
order structure. By the nature of this method the area protected by H1/H5
histones appears symmetrical around the centre of the nucleosomal DNA on the dyad
axis (position S[0]), but it can also be interpreted as a superposition of two
separate protected areas that are symmetrical around position S[0]. Protection by
the higher-order structure shows that the nucleosomes are oriented with their
S[0] positions inside the 30 nm fibre and that there is a minimum number of
nucleosomes required for this structure to be formed. We have also found that the
linker DNA is cut in a continuous (non-periodical) way and that there are
considerable amounts of nucleosomes at discrete distances of multiples of ten
nucleotides (10a nt) as well as stretches of nucleosomes positioned either at
random or at distances of (10a + 5)nt.
PMID- 9636699
TI - Trifluoroethanol stabilizes the pH 4 folding intermediate of sperm whale
apomyoglobin.
AB - 2,2,2-Trifluoroethanol (TFE) is known to stabilize peptide helices by
strengthening hydrogen bonds. On the other hand, TFE destabilizes native
proteins, as we confirm here, presumably by weakening the hydrophobic
interaction. The stability of the pH 4 folding intermediate of apomyoglobin is
known to depend both on the strength of the individual A, G, and H helices and on
hydrophobic interactions between helices. We ask which effect of TFE dominates in
this case: strengthening helices or weakening hydrophobic interactions between
helices? Protein stability is measured by denaturant-induced unfolding curves,
and two-state unfolding is tested by monitoring both far-UV CD and tryptophan
fluorescence emission. Low concentrations of TFE strongly stabilize the pH 4
folding intermediate. Moreover, low concentrations of TFE compensate for helix
destabilizing mutations in the A and G helices. Consequently, enhancing helix
propensity, rather than weakening the hydrophobic interaction, is the dominant
effect of TFE on the folding intermediate. This result agrees with earlier
mutational evidence that helix propensities are very important in determining the
stability of the pH 4 intermediate. Although TFE destabilizes native
holomyoglobin, as well as native lysozyme and ribonuclease A, nevertheless, TFE
stabilizes native apomyoglobin.
PMID- 9636701
TI - Trade-off between segregational stability and metabolic burden: a mathematical
model of plasmid ColE1 replication control.
AB - A model of ColE1 copy number control has been developed where molecular details
of replication are connected both to segregational stability and metabolic
burden. Efficient replication control reduces copy number variation and increases
segregational stability for a given average copy number. Copy number variation is
predicted to depend on the type of inhibition mechanism as well as RNA I and RNA
II turnover rate constants. It is shown that when both RNA I and RNA II
transcription frequencies and the rate constant for degradation of free RNA I are
very large, a hyperbolic inhibition mechanism must compensate with a 1.4 times
greater average copy number to obtain the same segregational stability as an
exponential inhibition mechanism. How sensitively the replication frequency
responds to changes in RNA I concentration depends on the type of inhibition
mechanism and the number of attempts to form an RNA II replication primer per
plasmid and cell cycle. If RNA I is too stable, it will not follow changes in
plasmid concentration closely, and when the transcription frequency for RNA I is
only slightly higher than for RNA II, RNA I concentration becomes randomized. In
both these cases, the proportionality between the single cell RNA I and plasmid
concentrations is lost and this impairs copy number control. Thresholds in the
rate for degradation of free RNA I as well as in RNA I and RNA II transcription
frequencies have been computed, where an increase in these rate constants has a
negligible effect on segregational stability but a corresponding decrease leads
to segregational disaster. This indicates that there exists a well defined
optimal set of rate constants where the regulation system works well without
excessive metabolic load. A number of new experiments are suggested to address
features of particular importance for the evolution of ColE1 copy number control.
PMID- 9636702
TI - Synthesis and characterisation of oligodeoxynucleotides containing thio analogues
of (6-4) pyrimidine-pyrimidinone photo-dimers.
AB - A method for the preparation of an oligodeoxynucleotide, 20 bases in length,
containing centrally located thio analogues of (6-4) pyrimidine-pyrimidinone
thymine photo-dimers is reported. The approach is based on the selective
irradiation, at 350 nm, of a Tp4ST (4ST = 4-thiothymidine) step within a 20-mer
having the sequence: d(ACTCGGACCT(4sT)CGCTGTGAT). Conversion of the S5-(6-4)/S5
thietane pyrimidine-pyrimidinone, initially formed, to its S5-Dewar isomer is by
a subsequent irradiation at 300 nm. Both of the photo-dimer-containing
oligonucleotides were purified by HPLC (ion exchange and reverse phase) and
characterised by base composition analysis. The S5-(6-4)/S5-thietane pyrimidine
pyrimidinone containing 20-mer has a characteristic UV absorbance at 320 nm and
exhibits strong fluorescence when excited at this wavelength. As expected,
conversion to the S5-Dewar isomer abolished both the 320 nm absorbance and the
fluorescence emission. The lengths of the oligonucleotides produced allowed the
formation of stable double-stranded DNA, by hybridisation to a complementary
sequence. Examination of these duplexes by circular dichroism spectroscopy showed
that they formed B-DNA, with little changes to their gross structure as compared
to the parent duplex. However, local structural perturbations in the region of
the photo-dimer cannot be excluded. The S5-(6-4)/S5-thietane photoproduct lowered
the tm by 10.5 deg. C and the Dewar isomer by 12 deg. C. The degree of curvature
induced in the DNA sequence by the introduction of the photo-dimers was assessed
by analysing the migration of modified and unmodified multimer ladders on
polyacrylamide gels. Both photoproducts induced considerable bending into the
DNA. A comparison with a six-base-pair T tract, a bending standard that has a
known bend angle of 19 degrees, gave values of around 47 degrees for the S5-(6
4)/S5-thietane product and about 28 degrees for the S5-Dewar isomer.
PMID- 9636703
TI - DNA binding discrimination of the murine DNA cytosine-C5 methyltransferase.
AB - Mammalian DNA cytosine-C5 methyltransferase modifies the CpG dinucleotide in the
context of many different genomic sequences. A rigorous DNA binding assay was
developed for the murine enzyme and used to define how sequences flanking the CpG
dinucleotide affect the stability of the enzyme:DNA complex. Oligonucleotides
containing a single CpG site form reversible 1:1 complexes with the enzyme that
are sequence-specific. A guanine/cytosine-rich 30 base-pair sequence, a mimic of
the GC-box cis-element, bound threefold more tightly than an adenine/thymine-rich
sequence, a mimic of the cyclic AMP responsive element. However, the binding
discrimination between hemi- and unmethylated forms of these DNA substrates was
small, as we previously observed at the K(m)DNA level (Biochemistry, 35, 7308
7315 (1996)). Single-stranded substrates are bound much more weakly than double
stranded DNA forms. An in vitro screening method was used to select for CpG
flanking sequence preferences of the DNA methyltransferase from a large,
divergent population of DNA substrates. After five iterative rounds of increasing
selective pressure, guanosine/cytosine-rich sequences were abundant and
contributed to binding stabilization for at least 12 base-pairs on either side of
a central CpG. Our results suggest a read-out of sequence-dependent
conformational features, such as helical flexibility, minor groove dimensions and
critical phosphate orientation and mobility, rather than interactions with
specific bases over the course of two complete helical turns. Thus, both studies
reveal a preference for guanosine/cytosine deoxynucleotides flanking the cognate
CpG. The enzyme specificity for similar sequences in the genome may contribute to
the in vivo functions of this vital enzyme.
PMID- 9636704
TI - The effects of salt on the TATA binding protein-DNA interaction from a
hyperthermophilic archaeon.
AB - This study investigates the thermodynamics of the interaction of the TATA box
binding protein (TBP) from Pyrococcus woesei (Pw) with an oligonucleotide
containing a specific binding site. Pw is a hyperthermophilic archeal organism
which exists under conditions of high salt and high temperature. A measurable
protein-DNA interaction only occurs at high salt concentrations. Isothermal
titration calorimetric binding studies were performed under a range of salts
(potassium chloride, potassium phosphate, potassium acetate and sodium acetate)
at varying concentrations (0.8 to 1.6 M). At the high salt concentrations used
the observed equilibrium binding constant increases with increasing salt
concentration. This is very different to the effect reported for all other
protein-DNA interactions which have been studied at lower salt concentrations.
Thermodynamic data suggest that the protein-DNA interaction at high salt
concentration is accompanied by the removal of large numbers of water molecules
from the buried hydrophobic surface area. In addition, the involvement of ions
appears to influence the binding which can be explained by binding of cations in
the interface between the electrostatically negative lateral lobes on the protein
and the negatively charged DNA.
PMID- 9636705
TI - Solution structure of a non-palindromic 16 base-pair DNA related to the HIV-1
kappa B site: evidence for BI-BII equilibrium inducing a global dynamic curvature
of the duplex.
AB - 1H and 31P NMR spectroscopy have been used together with molecular modelling to
determine the fine structure of a non-palindromic 16 bp DNA containing the NF
kappa B binding site. Much emphasis has been placed upon NMR optimization of both
two-dimensional 31P NMR techniques to extract structural information defining the
phosphodiester backbone conformation and selective homonuclear 2D COSY
experiments to determine sugar conformations. NMR data show evidence for a
dynamic behaviour of steps flanking the ten base-pairs of the NF-kappa B binding
site. A BI-BII equilibrium at these steps is demonstrated and two models for each
extreme conformation are proposed in agreement with NMR data. In the refined BII
structures, the NF-kappa B binding site exhibits an intrinsic curvature towards
the major groove that is magnified by the four flanking steps in the BII
conformation. Furthermore, the base-pairs are translated into the major groove.
Thus, we present a novel mode of dynamic intrinsic curvature compatible with the
DNA curvature observed in the X-ray structure of the p50-DNA complex.
PMID- 9636706
TI - Genome structure of mycobacteriophage D29: implications for phage evolution.
AB - Mycobacteriophage D29 is a lytic phage that infects both fast and slow-growing
mycobacterial species. The complete genome sequence of D29 reveals that it is a
close relative of the temperate mycobacteriophage L5, whose sequence has been
described previously. The overall organization of the D29 genome is similar to
that of L5, although a 3.6 kb deletion removing the repressor gene accounts for
the inability of D29 to form lysogens. Comparison of the two genomes shows that
they are punctuated by a large number of insertions, deletions, and substitutions
of genes, consistent with the genetic mosaicism of lambdoid phages.
PMID- 9636707
TI - Identification of target promoters for the Bacillus subtilis sigma X factor using
a consensus-directed search.
AB - The promoter selectivity of RNA polymerase (RNAP) can be altered by the
association with alternative sigma subunits. Bacillus subtilis hosts a multitude
of sigma factors, several of which coordinate the complex developmental program
culminating in endospore formation. Genome sequencing has revealed an
unanticipated seven new sigma factors of the highly divergent extracytoplasmic
function (ECF) sub-family. Virtually nothing is known regarding either the
promoter selectivity or the target genes for these newly identified sigma
factors. We have used saturation mutagenesis to define a promoter consensus for
recognition by one such ECF sigma factor, sigma X. The resulting consensus
sequence was used to identify candidate sigma X target sites. Three newly
identified sigma X-dependent promoters precede genes encoding regulatory
proteins: an AbrB homolog (Abh), a putative response regulator aspartate
phosphatase (RapD), and a regulator of autolysin expression (LytR). sigma X also
contributes to the expression of CsbB, a putative membrane-bound glucosyl
transferase that is partially controlled by the sigma B stress response sigma
factor. Since LytR modulates the expression of the major autolytic amidase and
CsbB may function in peptidoglycan synthesis or modification, we suggest that
sigma X participates in the regulation of peptidoglycan synthesis and turnover.
PMID- 9636708
TI - Different pathways for protein degradation by the FtsH/HflKC membrane-embedded
protease complex: an implication from the interference by a mutant form of a new
substrate protein, YccA.
AB - Escherichia coli FtsH (HflB) is a membrane-bound and ATP-dependent zinc
metalloproteinase, which forms a complex with a pair of periplasmically exposed
membrane proteins, HflK and HflC. It is the protease that degrades uncomplexed
forms of the SecY subunit of protein translocase. Here, we characterized a new
class of SecY-stabilizing mutation on the E. coli chromosome. The mutation
(yccA11) is an internal deletion within a gene (yccA) known as an open reading
frame for a hydrophobic protein with putative seven transmembrane segments. The
YccA protein was found to be degraded in an FtsH-dependent manner in vivo and in
vitro, whereas the YccA11 mutant protein, lacking eight amino acid residues
within the amino-terminal cytoplasmic domain, was refractory to the degradation.
The yccA11 mutation exhibited partial dominance when overexpressed. Cross
linking, co-immunoprecipitation, and histidine tagging experiments showed that
YccA11 as well as YccA can associate with both the FtsH and the HflKC proteins.
Thus, the mutant YccA protein appeared to compete with SecY for recognition by
the FtsH proteolytic system and the residues deleted by the yccA mutation are
required for the initiation of proteolysis by FtsH. Interestingly, the inhibitory
action of YccA11 was mediated by HflKC, since the deletion of hflK-hflC
suppressed the yccA11 phenotype. The yccA11 mutation stabilized subunit a of the
proton ATPase F0 segment as well, but not the CII protein of bacteriophage lambda
or the sigma 32 protein. From these results we suggest that there are at least
two pathways for FtsH-dependent protein degradation, only one of which (probably
for membrane proteins) is subject to the HflKC-dependent interference by the
YccA11 mutant substrate.
PMID- 9636709
TI - Rat GTP cyclohydrolase I is a homodecameric protein complex containing high
affinity calcium-binding sites.
AB - Recombinant rat liver GTP cyclohydrolase I has been prepared by heterologous gene
expression in Escherichia coli and characterized by biochemical and biophysical
methods. Correlation averaged electron micrograph images of preferentially
oriented enzyme particles revealed a fivefold rotational symmetry of the doughnut
shaped views with an average particle diameter of 10 nm. Analytical
ultracentrifugation and quantitative scanning transmission electron microscopy
yielded average molecular masses of 270 kDa and 275 kDa, respectively. Like the
Escherichia coli homolog, these findings suggest that the active enzyme forms a
homodecameric protein complex consisting of two fivefold symmetric pentameric
rings associated face-to-face. Examination of the amino acid sequence combined
with calcium-binding experiments and mutational analysis revealed a high
affinity, EF-hand-like calcium-binding loop motif in eukaryotic enzyme species,
which is absent in bacteria. Intrinsic fluorescence measurements yielded an
approximate dissociation constant of 10 nM for calcium and no significant binding
of magnesium. Interestingly, a loss of calcium-binding capacity observed for two
rationally designed mutations within the presumed calcium-binding loop of the rat
GTP cyclohydrolase I yielded a 45% decrease in enzyme activity. This finding
suggests that failure of calcium binding may be the consequence of a mutation
recently identified in the causative GTP cyclohydrolase I gene of patients
suffering from dopa responsive dystonia.
PMID- 9636710
TI - Structure of the Drosophila projectin protein: isoforms and implication for
projectin filament assembly.
AB - The protein composition of the various muscle types in Drosophila melanogaster
has been studied quite thoroughly and the analysis has revealed many differences
involving the usage of muscle specific isoforms of a given protein, as well as
the presence of proteins restricted to one muscle type. Drosophila projectin, the
giant protein component of the third filament is quite unusual as it not only
shows specific isoforms in various muscle types, but these isoforms are located
at different sarcomeric locations, I band in the IFM and A band in synchronous
muscles. This may suggest distinct functions for the projectin protein in various
muscles, as well as a different set of protein interactions for each projectin
isoform. Projectin is encoded by a single gene and the isoforms were proposed to
be the result of alternative splicing of a primary transcript. Here, we report
the nearly complete sequence of Drosophila projectin, as well as the possible
splicing patterns used to generate different isoforms. The overall domain
organization in projectin is composed of repeated motifs I and II in a few
specific patterns, similar to its Caenorhabditis homolog, twitchin. Sequence
similarity between twitchin and projectin further suggests how some domains may
possibly be important for protein interactions and/or functions. Alternative
splicing operates at the COOH terminus, leading to a shorter projectin protein
lacking some of the terminal motifs II and unique sequence. These isoforms are
discussed in view of projectin differential size and localization.
PMID- 9636711
TI - Structural studies of binding site tryptophan mutants in the high-affinity
streptavidin-biotin complex.
AB - Previous thermodynamic and computational studies have pointed to the important
energetic role of aromatic contacts in generating the exceptional binding free
energy of streptavidin-biotin association. We report here the crystallographic
characterization of single site tryptophan mutants in investigating structural
consequences of alterations in these aromatic contacts. Four tryptophan residues,
Trp79, Trp92, Trp108 and Trp120, play an important role in the hydrophobic
binding contributions, which along with a hydrogen bonding network and a flexible
binding loop give rise to tight ligand binding (Ka approximately 10(13) M-1). The
crystal structures of ligand-free and biotin-bound mutants, W79F, W108F, W120F
and W120A, in the resolution range from 1.9 to 2.3 A were determined. Nine data
sets for these four different mutants were collected, and structural models were
refined to R-values ranging from 0.15 to 0.20. The major question addressed here
is how these mutations influence the streptavidin binding site and in particular
how they affect the binding mode of biotin in the complex. The overall folding of
streptavidin was not significantly altered in any of the tryptophan mutants. With
one exception, only minor deviations in the unbound structures were observed. In
one crystal form of unbound W79F, there is a coupled shift in the side-chains of
Phe29 and Tyr43 toward the mutation site, although in a different crystal form
these shifts are not observed. In the bound structures, the orientation of biotin
in the binding pocket was not significantly altered in the mutant complex.
Compared with the wild-type streptavidin-biotin complex, there were no additional
crystallographic water molecules observed for any of the mutants in the binding
pocket. These structural studies thus suggest that the thermodynamic alterations
can be attributed to the local alterations in binding residue composition, rather
than a rearrangement of binding site architectures.
PMID- 9636712
TI - Structures of two novel crystal forms of Naja naja naja phospholipase A2 lacking
Ca2+ reveal trimeric packing.
AB - Three crystal forms of Naja naja naja phospholipase A2 were discovered through
random crystallization screening, including two heretofore uncharacterized forms.
The crystallization conditions for both of these novel crystal forms are Ca(2+)
free whereas previously reported conditions include Ca2+. One of the new crystal
forms has a cubic lattice in the space group P2(1)3 (a = b = c = 69.24 A), the
other has an orthorhombic lattice in the space group P2(1)2(1)2(1) (a = 67.22 A,
b = 73.48 A, c = 87.52 A) and a previously characterized crystal belong to the
tetragonal space group P4(3)2(1)2 (a = b = 88.6 A, c = 107.4 A). The structure
from the cubic crystal form has been determined to 1.8 A and refined to an R
factor of 17% while the structure from the orthorhombic form has been determined
to 2.65 A and has been refined to an R-factor of 21%. The determination of the
cubic structure extends the resolution to which structures of this molecule have
been determined from 2.3 A to 1.8 A. The two newly determined structures, in
combination with the previously determined structure, generate an informative
structural ensemble from which structural changes due to Ca2+, which is required
for catalysis, and the effect of crystal contacts on side-chain conformations and
oligomeric association can be inferred. Both of the newly determined structures
reveal a trimeric oligomer as observed in the tetragonal structure; this appears
to be a unique feature of the Naja naja naja enzyme.
PMID- 9636713
TI - Crystal structure of ribosomal protein S8 from Thermus thermophilus reveals a
high degree of structural conservation of a specific RNA binding site.
AB - S8 is one of the core ribosomal proteins. It binds to 16 S RNA with high affinity
and independently of other ribosomal proteins. It also acts as a translational
repressor in Escherichia coli by binding to its own mRNA. The structure of
Thermus thermophilus S8 has been determined by the method of multiple isomorphous
replacement at 2.9 A resolution and refined to a crystallographic R-factor of
16.2% (Rfree 27.5%). The two domains of the structure have an alpha/beta fold and
are connected by a long protruding loop. The two molecules in the asymmetric unit
of the crystal interact through an extensive hydrophobic core and form a tightly
associated dimer, while symmetry-related molecules form a joint beta-sheet of
mixed type. This type of protein-protein interaction could be realized within the
ribosomal assembly. A comparison of the structures of T. thermophilus and
Bacillus stearothermophilus S8 shows that the interdomain loop is eight residues
longer in the former and reveals high structural conservation of an extensive
region, located in the C-terminal domain. From mutational studies this region was
proposed earlier to be involved in specific interaction with RNA. On the basis of
these data and on the comparison of the two structures of S8, it is proposed that
the three-dimensional structure of specific RNA binding sites in ribosomal
proteins is highly conserved among different species.
PMID- 9636714
TI - The three-dimensional structure of the nitrogen regulatory protein IIANtr from
Escherichia coli.
AB - The bacterial rpoN operon codes for sigma 54, which is the key sigma factor that,
under nitrogen starvation conditions, activates the transcription of genes needed
to assimilate ammonia and glutamate. The rpoN operon contains several other open
reading frames that are cotranscribed with sigma 54. The product of one of these,
the 17.9 kDa protein IIANtr, is homologous to IIA proteins of the
phosphoenolpyruvate:sugar phosphotransferase (PTS) system. IIANtr influences the
transcription of sigma 54-dependent genes through an unknown mechanism and may
thereby provide a regulatory link between carbon and nitrogen metabolism. Here we
describe the 2.35 A X-ray structure of Escherichia coli IIANtr. It is the first
structure of a IIA enzyme from the fructose-mannitol family of the PTS. The
enzyme displays a novel fold characterized by a central mixed parallel/anti
parallel beta-sheet surrounded by six alpha-helices. The active site His73 is
situated in a shallow depression on the protein surface.
PMID- 9636715
TI - Determination of the three-dimensional solution structure of Raphanus sativus
antifungal protein 1 by 1H NMR.
AB - Raphanus sativus Antifungal Protein 1 (Rs-AFP1) is a 51 amino acid residue plant
defensin isolated from radish (Raphanus sativus L.) seeds. The three-dimensional
structure in aqueous solution has been determined from two-dimensional 1H NMR
data recorded at 500 MHz using the DIANA/REDAC calculation protocols.
Experimental constraints consisted of 787 interproton distances extracted from
NOE cross-peaks, 89 torsional constraints from 106 vicinal interproton coupling
constants and 32 stereospecific assignments of prochiral protons. Further
refinement by simulated annealing resulted in a set of 20 structures having
pairwise root-mean-square differences of 1.35(+/- 0.35) A over the backbone heavy
atoms and 2.11(+/- 0.46) A over all heavy atoms. The molecule adopts a compact
globular fold comprising an alpha-helix from Asn18 till Leu28 and a triple
stranded beta-sheet (beta 1 = Lys2-Arg6, beta 2 = His33-Tyr38 and beta 3 = His43
Pro50). The central strand of this beta-sheet is connected by two disulfide
bridges (Cys21-Cys45 and Cys25-Cys47) to the alpha-helix. The connection between
beta-strand 2 and 3 is formed by a type VIa beta-turn. Even the loop (Pro7 to
Asn17) between beta-strand 1 and the alpha-helix is relatively well defined. The
structure of Raphanus sativus Antifungal Protein 1 features all the
characteristics of the "cysteine stabilized alpha beta motif". A comparison of
the complete structure and of the regions important for interaction with the
fungal receptor according to a mutational study, is made with the structure of
gamma-thionin, a plant defensin that has no antifungal activity. It is concluded
that this interaction is both electrostatic and specific, and some possible
scenarios for the mode of action are given.
PMID- 9636716
TI - Conformational stability and thermodynamics of folding of ribonucleases Sa, Sa2
and Sa3.
AB - Ribonucleases Sa, Sa2, and Sa3 are three small, extracellular enzymes produced by
different strains of Streptomyces aureofaciens with amino acid sequences that are
50% identical. We have studied the unfolding of these enzymes by heat and urea to
determine the conformational stability and its dependence on temperature, pH,
NaCl, and the disulfide bond. All three of the Sa ribonucleases unfold reversibly
by a two-state mechanism with melting temperatures, Tm, at pH 7 of 48.4 degrees C
(Sa), 41.1 degrees C (Sa2), and 47.2 degrees C (Sa3). The Tm values are increased
in the presence of 0.5 M NaCl by 4.0 deg. C (Sa), 0.1 deg. C (Sa2), and 7.2 deg.
C (Sa3). The Tm values are decreased by 20.0 deg. C (Sa), 31.5 deg. C (Sa2), and
27.0 deg. C (Sa3) when the single disulfide bond in the molecules is reduced. We
compare these results with similar studies on two other members of the microbial
ribonuclease family, RNase T1 and RNase Ba (barnase), and with a member of the
mammalian ribonuclease family, RNase A. At pH 7 and 25 degrees C, the
conformational stabilities of the ribonucleases are (kcal/mol): 2.9 (Sa2), 5.6
(Sa3), 6.1 (Sa), 6.6 (T1), 8.7 (Ba), and 9.2 (A). Our analysis of the stabilizing
forces suggests that the hydrophobic effect contributes from 90 to 110 kcal/mol
and that hydrogen bonding contributes from 70 to 105 kcal/mol to the stability of
these ribonucleases. Thus, we think that the hydrophobic effect and hydrogen
bonding make large but comparable contributions to the conformational stability
of these proteins.
PMID- 9636717
TI - A graph-theoretic algorithm for comparative modeling of protein structure.
AB - The interconnected nature of interactions in protein structures appears to be the
major hurdle in preventing the construction of accurate comparative models. We
present an algorithm that uses graph theory to handle this problem. Each possible
conformation of a residue in an amino acid sequence is represented using the
notion of a node in a graph. Each node is given a weight based on the degree of
the interaction between its side-chain atoms and the local main-chain atoms.
Edges are then drawn between pairs of residue conformations/nodes that are
consistent with each other (i.e. clash-free and satisfying geometrical
constraints). The edges are weighted based on the interactions between the atoms
of the two nodes. Once the entire graph is constructed, all the maximal sets of
completely connected nodes (cliques) are found using a clique-finding algorithm.
The cliques with the best weights represent the optimal combinations of the
various main-chain and side-chain possibilities, taking the respective
environments into account. The algorithm is used in a comparative modeling
scenario to build side-chains, regions of main chain, and mix and match between
different homologs in a context-sensitive manner. The predictive power of this
method is assessed by applying it to cases where the experimental structure is
not known in advance.
PMID- 9636718
TI - X-ray diffuse scattering and rigid-body motion in crystalline lysozyme probed by
molecular dynamics simulation.
AB - Rigid-body motions are determined from a 1 ns molecular dynamics simulation of
the unit cell of orthorhombic hen egg-white lysozyme and their contribution to X
ray diffuse scattering intensities are examined. Using a dynamical cluster
technique, groups of backbone atoms that move as approximately rigid bodies are
derived from the intramolecular interatomic fluctuation matrix. These groups tend
to be local in the sequence or connected by disulphide bonds, and contain on
average five residues each, X-ray diffuse scattering patterns, which are
sensitive to collective motions, are calculated from the full simulation
trajectory (including all the protein degrees of freedom). The results reproduce
the main features of the experimental scattering. Diffuse scattering is also
calculated from fitted trajectories of the rigid bodies. The full simulation
diffuse scattering and atomic displacements are found to be well reproduced by a
model in which the backbone atoms form the rigid groups determined using the
dynamical cluster technique and the individual side-chains behave as separate
rigid bodies: the resulting R-factor with the full simulation scattering is 5%.
Quantitatively poorer agreement is obtained from trajectories in which the
secondary structural elements of the protein are considered rigid. Rigid whole
molecule and domain motions make only minor contributions to the protein atom
displacements. Finally, correlations in the interatomic fluctuations are examined
directly using a canonical method.
PMID- 9636719
TI - [Talking with our readers].
PMID- 9636720
TI - [Magnetic resonance of the elbow: technique optimization and definitions of
normal anatomical features and their variations].
AB - INTRODUCTION: MRI is a very accurate technique to study the elbow joint, tendon,
ligament and chondral structures. In the last years elbow disorders were
described by several MR investigators, while we studied MR capabilities in
depicting normal elbow anatomy. This investigation might permit the correct
differentiation of normal from abnormal MR patterns. MATERIAL AND METHODS: Eleven
healthy volunteers (6 men and 5 women, mean age: 27.5 years) were examined. All
studies were performed on a 1.5 T imager (Magnetom SP 4000) with two types of
receiver: the knee coil was used in 7 volunteers examined in the prone position,
with the arm above their head, the elbow extended and the forearm supine and the
shoulder coil was used in 4 volunteers examined in the prone position, with the
arm above their head, the elbow flexed and the forearm prone. We acquired T1
weighted SE sequences (TR/TE = 690/15 ms, FA 90 degrees, MA 256 x 512, NEX 2,20 3
mm sections with .3-mm interslice gap, FOV 20-22 cm) on the axial, coronal and
sagittal planes and T2-weighted GE sequences (TR/TE = 450/10 ms, MA 256 x 256, 3
NEX, 18 4-mm sections with .4-mm interslice gap, FOV 13-18 cm) on the coronal
plane. Two MR-expert radiologists studied the images and identified the main
anatomical structures of the elbow and 12 smaller reference elements (2
anatomical variants, 4 ligaments, 3 nerves and 3 arteries) describing their MR
appearance and pointing out the most effective planes for their representation.
Finally, the image quality of the knee coil was compared with that of the
shoulder coil. RESULTS: All bones were clearly depicted on the coronal and axial
planes, while the semilunar groove and its anatomical variants were best seen on
the sagittal plane. The joint cartilage was best depicted on the coronal plane
with T2-weighted GE sequences. Collateral ligaments were best seen with the elbow
extended and the forearm supine (knee coil), on coronal T1-weighted SE images,
where the radial and ulnar collateral ligaments were visible in 71.4% and 85.7%
of the subjects, respectively. Annular ligaments, muscles and tendons were best
demonstrated on the axial plane with the elbow extended and the forearm supine
(knee coil), while the triceps tendon was best recognized on the sagittal plane
with the elbow flexed and the forearm prone (shoulder coil). Vessels and nerves
were also best seen on the axial plane with the elbow extended and the forearm
supine; in particular, the median nerve was visible in 71.4% of the subjects.
DISCUSSION AND CONCLUSION: MRI is very effective in representing elbow anatomical
structures. Its accuracy depends on elbow (flexed or extended) and forearm (prone
or supine) position. The coronal images with the elbow extended and the forearm
supine (knee coil) are the most effective to show the ligaments and the joint
surfaces between the radial head and the coronoid process of ulna with the
capitellum and trochlea of distal humerus, while the axial images best depicted
the muscles, vessels and nerves. The coronal and axial planes, with the elbow
flexed and the forearm prone (shoulder coil) are poorly effective for anatomical
detailing, even though this position is more comfortable for the patient, while
the sagittal plane is best suited to depict the triceps tendon. This position may
be used when the elbow cannot be fully extended or when the triceps tendon is
studied.
PMID- 9636721
TI - Diagnostic imaging of the early slipped capital femoral epiphysis.
AB - INTRODUCTION: Early slipped capital femoral epiphysis (ESCFE) can be treated
surgically, with excellent results, if it is diagnosed in its initial stage;
however, the rate of late or missed diagnoses remains surprisingly high. PURPOSE:
We compared radiography, US and MR sensitivity in ESCFE diagnosis. MATERIAL AND
METHODS: We examined 21 symptomatic overweight patients (15 boys and 6 girls)
aged 9 to 15 years with anteroposterior radiographs; frog leg images were not
acquired in 3 cases only. US was performed in 19 cases and the images acquired
with 5-7.5 MHz probes on the sagittal plane parallel to the femoral neck. MRI was
performed in 9 cases, with coronal and sagittal T1 SE and T2* GE images. RESULTS:
Our sensitivity rates were 66% for anteroposterior radiography (6 false
negatives), 80% for combined anteroposterior and frog leg images (3 false
negatives), 95% for US (1 false negative) and 88% for MRI (1 false negative).
DISCUSSION AND CONCLUSION: We believe that US is the method of choice in ESCFE
diagnosis; if it is negative, but pain persists, MRI should be performed.
PMID- 9636722
TI - [Ozone therapy in lumbar sciatic pain].
AB - INTRODUCTION: Medical ozone is a mixture of oxygen and ozone which can be used
for several medical applications. Ozone was first applied clinically to the
treatment of lumbar sciatic pain peridurally, while Pietrogrande was the first in
Italy to report on its intradiscal administration to treat nucleus polposus
herniation. On account of these considerations, we have decided to introduce this
method in our Institute (I.C.O.T. Latina) as an alternative to surgery in the
treatment of lumbar sciatic pain supported by an intradiscal hernia. MATERIAL AND
METHODS: September, 1995, to April, 1997, we treated more than 1000 patients with
intradiscal ozone infiltration. We prospectively analyzed the first 50 patients,
with 6 months' follow-up at least; all of them were preliminarily submitted to
clinical examination, electromyography, CT and MRI. After local anesthesia, we
injected the disk, with 18-20 G needles and under CT or fluoroscopic guidance,
with 12 ml of a mixture of oxygen and ozone at a concentration of 20-30
micrograms/ml. The treatment was repeated two or three more times at intervals of
3, 15 or, when necessary, 30 days. After each treatment, CT follow-ups were
carried out and the final follow-up was made 3 months later. RESULTS: We divided
our results into clinical and instrumental. As for clinical response, we had 68%
positive results (40% excellent, 28% good) and 32% negative results (10% of
patients underwent surgery and 22 are under medical and physical treatment). As
for CT response, we had 82% positive results (36% excellent, 46% good), while no
major changes between pre- and post-treatment CT findings in the remaining 18% of
cases. CONCLUSIONS: Ozone therapy, thanks to its ease of execution and
noninvasiveness, permits the successful outpatient treatment of lumbar sciatic
pain. Moreover, the lack of major complications and the good results obtained
compared to other methods, such as chemonucleolysis, percutaneous automated
discectomy, microsurgery and conventional surgery, suggest that ozone therapy can
be considered the treatment of choice for lumbar sciatic pain and a valid
alternative to surgery in many cases.
PMID- 9636723
TI - [Digital panoramic radiography in patients with rigid internal fixations devices
after maxillofacial surgery].
AB - INTRODUCTION: Digital techniques have found promising applications in dental
radiology in the recent past, namely with radiovisiography and digital panoramic
radiography. These images present some features making them particularly
interesting for alveolar bone studies. MATERIAL AND METHODS: Digital panoramic
radiography with light-emitting phosphors was performed on 16 patients during
postoperative follow-up. The patients were previously submitted to multiple
maxillofacial osteosynthesis with rigid internal fixation devices (32 miniplates,
12 microplates, 14 screws). Digital images were always observed and printed with
analogic-like and Xeroradiographic-like post-processing. RESULTS: Digital
panoramic radiographs yielded clear and effective images of the maxillary and
mandibular arches and of surgical osteosynthesis, as demonstrated by a
retrospective evaluation performed by three independent observers on a blind
basis (score 3: 60.42%), with no major interobserver differences (p = .7286).
Xeroradiographic-like images were the most effective in depicting bone structures
and osteosynthesis materials, thanks to their better detailing and typically
lower overall contrast. Among the drawbacks of the digital technique, reduced
cassette size may prevent the full view of the mandibular arch from the symphysis
to both condylar regions. The edge effect, which is typical of Xeroradiographic
images, may mask useful details within the trabecular bone close to metal
implants. This effect was present in some of our cases, but it was seldom
disturbing according to our retrospective evaluation (score 3: 53.40%), with good
interobserver agreement (p = .1117). CONCLUSION: Digital panoramic radiography
proves to be a useful tool to study metal implants after maxillofacial surgery as
well as alveolar bone structure. The digital technique markedly reduces the
radiation dose to the patient, which is very important for an X-ray examination
that must be repeated several times, often in young subjects.
PMID- 9636724
TI - [Non-palpable lesions of the breast. Retrospective analysis of mammographic and
ultrasonographic indications for surgery].
AB - INTRODUCTION: The differential diagnosis of malignancy in small foci of
microcalcifications or in extremely small nodes can be difficult. We carried out
a retrospective analysis of integrated mammographic and US results, correlated
with histologic data, to assess the limitations of each method and to optimize
and benign/malignant ratio. MATERIALS AND METHODS: Our series consisted of 485
nonpalpable breast lesions submitted to histologic examination after vegetable
charcoal marking. We gave each lesion an 0-5 score according to the degree of
diagnostic doubt/suspicion after mammography and US, which results were
correlated with histologic data to assess the carcinoma frequency in the various
groups identified. RESULTS: The analysis of mammographic and US images showed
that the most frequent mammographic alteration in the lesions submitted to biopsy
was an isolated cluster of microcalcifications (40.99%): of these, 36.86% were
neoplastic. The nodules submitted to biopsy, which were 29.81% of the total,
showed a cancer rate (36.80%) very similar to that of the microcalcifications.
The carcinoma rate rose to 37.93% when the microcalcifications were associated
with nodes. The highest carcinoma rates, i.e., 52.94% and 66.66%, respectively,
were found in parenchymal distortions, either isolated or associated with
microcalcifications, which however were only 7.03% and 3.10%, respectively, of
the total number of cases. DISCUSSION AND CONCLUSIONS: Our study showed that: 1)
a highly suspicious US result must be seriously considered when a negative
mammography has poor intrinsic contrast; 2) a highly suspicious US image with a
little suspicious good contrast mammography requires further confirmation before
surgery is planned; 3) when the mammographic finding is mid-to-highly suspicious,
further investigations are needed even if US is negative. To conclude, even
though the histologic examination of nonpalpable breast lesions involves
performing a biopsy, we believe this is acceptable when performed on an
outpatient basis, under local anesthesia and removing a limited amount of tissue
only. The benign/malignant ratio ranges 2 to 1.5: if it is further reduced (below
1.5), there will be the risk of missing some early neoplastic lesions.
PMID- 9636725
TI - [Role of diagnostic imaging of the breast in patients treated with postsurgical
radiotherapy or presurgical radiotherapy or chemotherapy].
AB - INTRODUCTION: In the last 25 years, random trials on the advantages of combined
surgery and irradiation/chemotherapy of breast cancer demonstrated similar
survival rates to those of massive surgery. However, both irradiation and
chemotherapy have advanced and now yield good local control of the disease, so
that even large breast cancers can be made operable. Breast cancer follow-up is
carried out with imaging and clinical examinations to detect early locoregional
recurrences, contralateral lesions and distant recurrences: to this purpose, we
carried out a comparative study of all imaging modalities. MATERIAL AND METHODS:
We retrospectively reviewed the data of 42 breast cancer (T2-T3 N0-N+) patients
of the Senology Center of the Catholic University (Rome, Italy) treated with
irradiation and/or chemotherapy for tumor debulking to permit conservative
surgery. We investigated the sensitivity and the indications of mammography, B
mode and color Doppler US and MRI in measuring the exact tumor size and detecting
locoregional metastatic nodes. RESULTS: After 3 years' treatment, our recurrence
rate (19%) is a little higher than those in the major international trials (4.2
9% and 5 tears). The recurrence was on the surgical scar in 75% of cases (6/8),
while multifocal tumors were found in 25% of cases. US was the most accurate
method in measuring tumor size in 90% of cases (18/20), while mammography
frequently overstaged the lesion and yielded exact measurements in 65% of cases
(13/20). MRI was as accurate as US, but this technique is too expensive and
little available in Italy. US accurately diagnosed lymph node recurrences (70%
sensitivity), but MR rate was even higher (80%), while mammography and color
Doppler US had only 5-10%. As for treatment outcome, an irregular and blurred
nodule or multifocal lesions at mammography indicate poor/no response, while a
much smaller radial scar than at previous similar follow-ups indicates treatment
success. CONCLUSIONS: When correctly integrated, mammographic, US and MR patterns
permit exact tumor size measurement and show possible locoregional lymph node
involvement in the patients submitted to conservative surgery and
irradiation/chemotherapy. In contrast, color Doppler findings remain poorly
specific in this disease, with about 55% sensitivity. Therefore, radiologic
studies, with clinical and laboratory data, have a major prognostic value in
assessing the biological response to combined treatment.
PMID- 9636726
TI - [Clinico-radiologic problems in the study of the male breast in gynecomastia].
AB - INTRODUCTION: Gynecomasty is usually classified as normal of abnormal, except for
25% of cases which are classified as idiopathic because their causes and
pathogenesis remain unknown. Gynecomasty is diagnosed mainly on clinical grounds,
while integrated imaging, sometimes combined with cytology, is used to
distinguish benign from malignant forms. Bilateral gynecomasty is easy to
diagnose, especially when patients report assuming particular drugs or present
other risk factors, but unilateral or asymmetrical gynecomasty is a diagnostic
problem. Primary male breast cancer usually presents as a unilateral hard mass,
often infiltrating the dermis and with early lymph node metastases; it is
associated with gynecomasty in 20% of cases. MATERIAL AND METHODS: We examined 76
men (age range, 15-75 years) referred for breast enlargement; the patients with
radiologic findings of breast adiposis were not included in our series. All
patients were submitted to standard projection mammography with a high resolution
dedicated film and to real time US with high frequency probes (7.5-12 MHz).
RESULTS: Breast enlargement was unilateral in 48% of cases and bilateral in 52%.
The radiologic patterns, compared with histologic or clinical-therapeutic follow
up, permitted the correct diagnosis in 72 of 76 patients (94%). The extant four
patients had chronic inflammation (3 cases) and a malignant tumor with
questionable imaging features. Overall imaging findings were: 55 cases (72%) of
actual gynecomasty--unilateral in 17 and bilateral in 38 cases--9 unilateral
malignant tumors (12%), eleven cases of inflammation (14%) and 1 case (2%) of
unilateral metastasis from plasmocytoma. Sixteen (29%) actual gynecomasty
patients (21% of the whole series) had a nodular form (unilateral in 6 and
bilateral in 10 cases), 23 (42% and 30% of the whole series) had a dendritic form
(unilateral in 7 and bilateral in 16 cases) and 16 (29%, 21% of the whole series)
had a glandular form. CONCLUSIONS: Diagnosing gynecomasty is relatively easy in
the patients with bilateral forms with a positive history of associated exogenous
or endogenous factors, while focal unilateral or asymmetrical forms are difficult
to distinguish into benign and malignant. The radiologic pattern may be
questionable especially in chronic inflammation and in some malignant forms and
must therefore be integrated with cytologic or surgical findings.
PMID- 9636727
TI - Hodgkin disease and non-Hodgkin lymphoma: plain chest radiographs and chest
computed tomography of thoracic involvement in previously untreated patients.
AB - PURPOSE: To provide further information about the presentation of thoracic
involvement in Hodgkin disease and non-Hodgkin lymphoma and to compare chest
radiography with chest CT findings. MATERIALS AND METHODS: We reviewed the chest
radiographs and the CT images of 100 Hodgkin and 100 non-Hodgkin patients, all of
them untreated. Our data were compared with those of literature series: the
latest study comparing the different patterns of Hodgkin and non-Hodgkin disease
appeared in 1976 and it compared chest radiography with conventional tomography,
not with CT. RESULTS: Intrathoracic involvement (75% vs 48%) and adenopathy (74%
vs 28%) were more frequent in Hodgkin than in non-Hodgkin lymphoma. Ninety-nine
per cent of the patients with intrathoracic involvement (74/75) had nodal
disease. Paratracheal/prevascular nodes were most frequently involved, namely in
72/74 Hodgkin (97%) and in 27/28 non-Hodgkin patients (96%). The lung parenchyma
was more often involved in non-Hodgkin (24%) than in Hodgkin (8%) patients; it
was associated with mediastinal/hilar adenopathy in all Hodgkin and in 10/24
(42%) non-Hodgkin cases. Parenchymal involvement was demonstrated with chest
radiography in 7/8 Hodgkin (88%) and in 13/24 non-Hodgkin patients (54%). Chest
radiography showed paratracheal/prevascular adenopathy more often in Hodgkin
(54/72, 75%) than in non-Hodgkin (15/27, 56%) cases. Subcarinal and internal
mammary adenopathy was poorly depicted with plain films, while hilar adenopathy
was generally identified with both CT and chest radiography. Chest radiography
usually missed posterior mediastinal and anterior diaphragmatic adenopathy.
CONCLUSIONS: The differences in the presentation of Hodgkin vs non-Hodgkin
disease are not sufficiently distinctive to permit radiographic differentiation
of the two conditions, but some patterns are helpful. Recognizing the frequency
of thoracic involvement and that of the additional CT findings in Hodgkin and non
Hodgkin patients makes a sound basis for lymphoma imaging.
PMID- 9636729
TI - [Diagnostic imaging of splenic cysts in children].
AB - INTRODUCTION: Nonparasitic splenic cysts are a rare finding: they can be
distinguished into true cysts (epidermoid or epithelial) cysts or false
(pseudocysts), depending on the presence/absence of an inner epithelial lining.
They are usually found during the second and third decade of life, although they
can also appear during childhood. They grow bigger in children, becoming
clinically apparent due to the symptoms of compression of adjacent structures.
The diagnosis is radiological, made with ultrasonography (US) and computed
tomography (CT). We report the US and CT patterns of splenic cysts to
differentiate true from false cysts. MATERIAL AND METHODS: Our series consists of
5 patients, aged 5-17 years, all examined with US and CT; one of them was also
submitted to plain abdominal radiography. Conventional CT was used in 2 cases and
helical CT in the extant 3. RESULTS: All examinations yielded useful clinical
informations. The only radiograph showed the rightward displacement of the
gastric gas bubble US always identified the cyst and its pertinence to splenic
parenchyma, although failing to assess the liquid/solid nature of a highly
echogenic cyst in one case. CT confirmed the cystic nature of all masses and
showed the lack of contrast enhancement of cyst walls and the presence of septa
or parietal calcifications. DISCUSSION: Radiological examinations, particularly
US and CT, can diagnose splenic cysts unquestionably, correctly defining the
relationships with adjacent organs. CT is more sensitive than US in detecting
septa or calcifications, which are definitely useful findings to distinguish true
from false cysts, since internal septa are more frequent in true cysts while
parietal calcifications are typical of pseudocysts. The final diagnosis, however,
is made at histology.
PMID- 9636728
TI - [Magnetic resonance angiography of coronary arteries: assessment in patients with
coronary stenosis and control after stent positioning].
AB - INTRODUCTION: Cardiovascular disease remains the leading cause of death in the
world. Invasive coronary angiography is currently the only clinical method
available to visualize the coronary arteries, with up to 20% of the procedures
demonstrating no evidence of severe coronary artery stenoses. We investigated the
role of two-dimensional (2D) coronary magnetic resonance angiography (MRA) in
patients with suspected coronary arteries disease and to check the placement and
the patency of previously placed coronary artery stents. MATERIAL AND METHODS:
Eleven patients with suspected coronary artery disease who underwent elective
cardiac catheterization with coronary angiography were examined with 2D coronary
MRA to detect coronary artery stenoses. Other 11 patients with 13 stented
coronary arteries (6 RCA, 5 LAD, 2 Lcx) were prospectively examined with MRA one
day to 8 months after stent placement. Eighteen amagnetic stents were imaged.
Imaging was performed with a 1.5 T MR unit (GE Signa Horizon Echo Speed) with a
phased array multicoil. Segmented k-space fast GE sequences were acquired with
and without fat suppression at several cardiac cycle phases within a single
breath-hold. Correlation with coronary angiography was performed in all patients.
RESULTS: Thirteen significant stenoses were found at coronary angiography in 11
coronary arteries. The sensitivity and specificity of MR coronary angiography, as
compared with conventional angiography, in correctly identifying the single
vessels with > 50% angiographic stenoses were 73% and 94%, respectively. The
corresponding positive and negative predictive values and accuracy were 88%; 84%
and 86%, respectively. As far as the study of coronary artery stents is
concerned, no MR-related adverse events were observed. The stents were visualized
as signal loss areas. The length of the signal loss corresponded to the length of
the stents in all 18 cases (r = 97). The patent blood flow distal to the stents
appeared as a high-signal band distal to the signal void, corresponding to stent
patency at coronary angiography. CONCLUSIONS: Although in an early stage of
technical development, 2D coronary MRA can depict 73% of hemodynamically severe
coronary artery stenoses. Moreover breath-hold coronary cine MRA is a safe
technique to visualize coronary artery stents. Stent site and patency can be
noninvasively studied with this technique.
PMID- 9636730
TI - [Biliary complications of liver transplant. Role of cholangiography with magnetic
resonance].
AB - INTRODUCTION: Orthotopic liver transplantation is considered the treatment of
choice in several hepatic conditions. The five-year patient survival rate is
approximately 75%, thanks to progress in both surgical techniques and
postoperative medical treatment. Biliary complications are one of the commonest
causes of failure and their prompt identification is difficult due to their
insidious clinical pattern and to the poor predictive value of a negative US
examination. To date, invasive contrast cholangiography (endoscopic retrograde
cholangiography and percutaneous transhepatic cholangiography) may be the only
way to identify anatomic abnormalities and it is therefore a necessary
examination when biliary obstruction is suspected. The aim of our work was to
assess the possible role of MR cholangiography in late biliary complications of
liver transplanted patients. MATERIAL AND METHODS: Twenty-three liver transplant
recipients (11 men and 12 women, mean age: 51.1 years) were submitted to MR
cholanglography using non-breath-hold, fat-suppressed three-dimensional turbo
spin echo sequences, (TR = 3000 ms, TE = 700 ms, ETL = 128). Our patients
presented with clinical, laboratory and US patterns doubtful for biliary
obstruction. The diagnostic confirmation was obtained at percutaneous
transhepatic cholangiography (four cases), endoscopic retrograde cholangiography
(eight cases), T-tube cholangiography (one case) or clinical follow-up (ten
cases). RESULTS: No biliary tract abnormalities were detected at MR
cholangiography in 11 cases. Twelve strictures were diagnosed in eleven patients
(9 anastomotic, two nonanastomotic/intrahepatic and one
nonanastomotic/extrahepatic, with associated anastomotic and nonanastomotic
strictures in two cases). MR cholangiography correctly defined the stricture site
and the dilation of the bile ducts above in all cases, with optimal correlation
with contrast cholangiographic findings. The common bile duct below the stricture
was visible in 9 of 10 patients with extrahepatic strictures on MR
cholangiography and in 8 of 10 patients on contrast cholangiograms. The distal
common bile duct was missed on both MR cholangiography and diagnostic
percutaneous transhepatic cholangiography in a patient only. The strictures were
correctly graded in 8 of 10 patients, with two cases of overestimation. Other
findings were a 1-cm stone proximal to the obstructed common bile duct, multiple
intrahepatic stones in another case and common bile duct kinking at the
anastomosis. CONCLUSIONS: MR cholangiography is a useful imaging method in the
follow-up of liver transplant recipients which can assess the biliary obstruction
and therefore permit to limit the use of invasive procedure only for
interventional purposes.
PMID- 9636731
TI - [Morpho-functional study of the kidney in patients with kidney disease and liver
disease with magnetic resonance].
AB - INTRODUCTION: We studied renal function and perfusion after the i.v. injection of
Gd-DTPA-BMA, a nonionic paramagnetic contrast agent, to assess renal morphology
and function in normal subjects, in renal insufficiency patients and in patients
with hepatic failure and normal renal function. The latter were chosen because
some patients with advanced hepatic failure may suffer from the hepatorenal
syndrome, characterized by severe vasoconstriction in the renal cortical vessels.
We investigated if dynamic MRI can detect early renal perfusion abnormalities in
the patients who will eventually develop this syndrome. MATERIAL AND METHODS:
Thirty MR examinations were carried out on 30 subjects after the i.v. injection
of Gd-DTPA-BMA. Our series consisted of: 10 normal subjects; 10 renal
insufficiency patients; 10 patients with hepatic failure and normal renal
function. MR examinations were performed on a Philips ACS II scanner operating at
1.5 T. Two sequences were carried out in all cases: T1-weighted SE and T1
weighted TGE sequences after the bolus injection of .1 mmol/kg contrast agent.
Renal longitudinal diameter and parenchymal thickness were measured in all cases
and signal intensity time curves were always made. The signal intensity of the
cortex, corticomedullary junction, medulla and pyelocaliceal system of each
kidney was measured using a region of interest (ROI). The signal intensity curves
were made considering quantitative parameters, including the area below the curve
(ASC), the peak (P) and the time to peak (T-P). RESULTS: Longitudinal diameter
and parenchymal thickness values were significantly lower in renal insufficiency
patients than in normal subjects. Four phases were demonstrated after i.v.
contrast agent injection in normal subjects, namely A) the cortical phase, B) the
corticomedullary junction phase, C) the medullary phase, D) the pyelocaliceal
phase. No signal intensity decrease in the medullary and pyelocaliceal curves was
observed in renal insufficiency patients. Signal intensity curves values were
lower in hepatic failure patients than in those with normal renal function.
Hepatic failure patients could be divided into two groups: 5 patients had low P
and ASC values and 4 had normal P and ASC values. The patients with lower P and
ASC values developed the hepatorenal syndrome within a few months of the MR
examination. DISCUSSION: Signal intensity decreased in the pyelocaliceal system
phase in normal subjects because of the high paramagnetic contrast agent
concentration. The lack of signal intensity decrease in renal insufficiency
patients was caused by the reduced capability of concentrating Gd-DTPA-BMA. Lower
signal intensity values in hepatic failure patients may be considered an early
sign of the hepatorenal syndrome.
PMID- 9636732
TI - ["Freddy frog" projection of the thorax: clinical applications in pediatric
oncohematology].
PMID- 9636733
TI - [Adjuvant radio-chemotherapy in cancer of the rectum treated with radical surgery
and with high risk of recurrence. Preliminary results of a prospective study].
AB - INTRODUCTION MATERIAL AND METHODS: From January, 1990, to December, 1995, 138
consecutive patients with radically resected stage II and III rectal and
rectosigmoid cancers were treated with adjuvant radiochemotherapy. Eighty-one
patients with 24 months' follow-up were assessable. Low anterior resection (LAR)
was performed in 64 (79%) patients and abdominoperineal resection (APR) in 17
(21%). Twentynine (36%) stage II and 52 (64%) stage III patients entered the
study. Within 45-60 days from surgery all patients received 5-Fluorouracil
chemotherapy at the dose of 500 mg/m2/iv/d 1-5, every 4 weeks, for six cycles.
Chemotherapy cycles 3 and 4 were administered at the same daily dose on
radiotherapy days 1-3 and 29-31. Radiotherapy total dose consisted of 45 Gy/1.8
Gy/day administered in 5 weeks with 18 MV photon beam to the pelvis with the four
field "box" technique. Perineal scar was encompassed only after APR. A boost dose
of 5.4 Gy to the tumor bed was given in 3 fractions of 1.8 Gy. Median follow-up
was 37 months (range: 24-74 months). RESULTS AND DISCUSSION: Overall recurrent
disease was reported in 28 of 81 patients (34%): local, systemic and both local
and systemic relapses in 9 (11%), 14 (17%) and 5 (6%) cases, respectively.
According to local extension, recurrence rates were 10% and 48% in stages II and
III, respectively. Five-year overall and disease-free actuarial survivals were
64% and 61%, respectively. Median time to relapse was 15 months (range: 7-43
months). Significant prognostic factors for better tumor control were: stage (II
vs III), disease site (proximal vs distal rectum), the surgical procedure (LAR vs
APR), the number of involved nodes (< or = 4 vs > 4) and no extracapsular node
invasion. The recommended dose of combined radiochemotherapy regimen used in this
trial was generally well tolerated. The incidence of any grade > or = 3 acute
toxicity (according to WHO grading) was 20% diarrhea, 6% tenesmus and 4%
myelosuppression. Five (6%) patients had cronic diarrhea and other 3 (4%)
radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS:
This study seems to provide similar survival and recurrence notes to other radio
chemotherapy regimens published in the literature. However, a more aggressive
approach is warranted in stage III patients considering the low 5-year survival
recorded.
PMID- 9636734
TI - [Assessment of radiation dose to patients in hysterosalpingography].
AB - INTRODUCTION: The optimization principle applied to the patient radioprotection,
recently introduced in Italian legislation, requires a careful analysis of the
working procedures and clinical protocols generally used in radiological
practice, to avoid unnecessary exposures with no loss in diagnostic information.
We carried out this analysis in hysterosalpingography, which is the radiological
examination usually performed on fertile women to detect uterine and tubal
conditions. MATERIALS AND METHODS: The dosimetric survey was carried out on 35
patients, 22 to 40 years old, to evaluate: a) entrance dose and dose x area
product; b) doses to the most irradiated organs, that is ovaries and uterus; c)
effective dose equivalent and effective dose. The doses were measured with LiF
thermoluminescent dosimeters, while an ionization chamber enabled us to the
calculate dose area product. Ovaries and uterus doses were calculated with a
Monte Carlo program using skin entrance exposure data and some technical
parameters of the examination. RESULTS: The good agreement of the results
obtained with both dosimetric methods demonstrated their equivalence in this
specific case where the use of a clinical protocol, with no lateral projection,
made the dosimeters lie always within the X-ray beam. DISCUSSION AND CONCLUSIONS:
The mean dose was 4.5 mGy for the ovaries and 6.2 mGy for the uterus. Following
the recommendations of the International Commission on Radiological Protection,
both effective dose equivalent, with a mean value of 2.0 mSv, and effective dose,
with a mean value of 1.95 mSv, were estimated. In conclusion, our results show
that the patient dose can be reduced by limiting the use of fluoroscopy, using
small size films and decreasing the number of exposures.
PMID- 9636735
TI - [Positron-emission tomography with fluorine-18-deoxyglucose in the staging and
control of patients with lymphoma. Comparison with clinico-radiologic
assessment].
AB - INTRODUCTION: The clinical applications of fluorine-18-deoxyglucose Positron
Emission Tomography (FDG PET) have been proposed on account of experimental
evidence of increased glucose metabolism in tumor cells. MATERIAL AND METHODS: We
examined 98 lymphoma patients--33 with Hodgkin and 65 with non-Hodgkin disease-
with FDG PET and compared its findings with those of clinical and conventional
radiologic studies. FDG PET was also used to follow-up 32 patients and the
results were once again compared with clinical and radiologic data. RESULTS:
During staging, 138 lesions were found, 82 of them (59%) in nodal and 56 (41%) in
extranodal locations. Extranodal tumor sites were found in 39 patients (40%),
namely 4 with Hodgkin (12%) and 35 with non-Hodgkin (54%) disease. FDG PET
findings were in agreement with clinical and radiologic results in all nodal and
extranodal lesions, since all of them exhibited abnormally increased FDG uptake.
PET detected new tumor sites in 6 patients. In the follow-up, agreement was
observed in the majority (78%) of lesions, 30 of them in complete regression, 15
in partial regression and 17 in progression; however, the diagnostic results were
in disagreement in the remaining (22%) tumor sites: no abnormal FDG uptake was
found in 9 cases despite the persistence of radiologic abnormalities (post
treatment fibrosclerosis). Slightly increased FDG uptake (residual disease) was
found in the other 8 lesions, where there was no clinical and/or radiologic
evidence of disease. CONCLUSIONS: FDG PET is a functional imaging technique
useful to diagnose lymphomas and providing metabolic characterization of cancer
abnormalities. Whole body PET permits the simultaneous assessment of nodal and
extranodal lymphoma localizations. During the follow-up, FDG PET permits better
monitoring of treatment effects than clinical and radiologic examinations.
PMID- 9636737
TI - [Plexiform schwannomatosis of the tibial nerve: study with MR and surgical
findings in a case].
PMID- 9636736
TI - [Posterior synovial ganglion with compression of the supraspinatus nerve,
infrequent cause of shoulder pain. Report of a case].
PMID- 9636738
TI - [Congenital hemangiopericytoma of the neck: ultrasonographic findings and with
MR].
PMID- 9636739
TI - [Fibroadenoma and carcinoma of the breast. Clinico-radiological considerations in
4 cases].
PMID- 9636740
TI - [Contribution of computerized tomography in the diagnosis of left extrapleural
hematoma secondary to spontaneous rupture of the thoraco- abdominal aorta. Report
of a case].
PMID- 9636741
TI - [Thrombophlebitis of the cavernous sinus. Magnetic resonance features in 2
cases].
PMID- 9636742
TI - [Splenic hemangiopericytoma: features with computerized tomography in 2 cases].
PMID- 9636743
TI - Torsion of a wandering spleen. Radiologic assessment in one case.
PMID- 9636744
TI - [Ultrasonographic diagnosis of gallbladder perforation caused by blunt abdominal
injury. Report of a case].
PMID- 9636745
TI - [Nephrocalcinosis caused by prolonged treatment with furosemide].
PMID- 9636746
TI - [Comments on the good topical usage of non-steroidal anti-inflammatory agents].
PMID- 9636747
TI - [Focus on bovine products].
PMID- 9636748
TI - [Histopathology of exogenous and idiopathic lucites and provocation phototests].
AB - OBJECTIVE: Provocative phototests are used regularly to explore photobiology in
patients with photodermatoses. Our objective was to determine the reliability of
the phototest in the diagnosis of idiopathic and exogenous light eruption in
order to identify the ideal date for the histological examination by correlation
between the histological aspects of light- triggered and spontaneous lesions.
PATIENTS AND METHODS: Among 66 patients, there were 48 with polymorphous light
eruptions, 13 with exogenous eruptions and 5 with chronic actinodermatitis. The
histological findings of the provocative phototests were correlated with the
clinical aspect, the date of biopsy and the histological aspect of the
spontaneous lesions. RESULTS: In polymorphous light eruptions (48 cases) this
test triggered a photoallergic reaction in 48% of the patients. There was a good
correlation between the histological findings and clinical features in 96% of the
cases. The histological image of the light-triggered lesion on day 6 was the
closest to that of the spontaneous lesion. In exogenous eruptions and chronic
actinodermatitis (18 cases), only 33% of the clinically positive phototests were
also positive at histological examination. The histological image was the same
for the provocative tests whether they were clinically positive or negative, with
signs of epidermal phototoxicity, regeneration acanthosis and moderate
perivascular lymphocyte infiltration of the superficial dermal layer.
CONCLUSIONS: Our findings confirmed that the phototest provides a good
correlation between histological findings and clinical presentation in idiopathic
polymorphous light eruptions, justifying simple clinical interpretation, but did
not demonstrate a rate of positive results as high as reported in the literature.
Day 6 is the ideal date for a phototest biopsy. In exogenous light eruptions, the
phototest is less reliable since the correlation between histology and clinical
presentation is weaker. It is difficult to reproduce spontaneous lesions with the
phototest, but if used, the phototest biopsy should be done on day 18.
PMID- 9636749
TI - [Prognostic factors and predictive signs of malignancy in adult dermatomyositis].
AB - INTRODUCTION: Prognosis in dermatomyositis is severe, partly due to the
development of cancer. The aim of this study was to identify factors predicting
cancer development and assess factors predicting reduced survival rate. PATIENTS
AND METHODS: A retrospective analysis of 32 cases of dermatomyositis diagnosed on
the basis of the Bohan and Peter criteria was performed. Diagnosis was certain in
7 cases, probable in 13 and possible in 5. There were thus 7 cases of pure
cutaneous dermatomyositis. Clinical and laboratory data were compared between
patients with and without cancer and between deceased and surviving patients.
RESULTS: Overall mortality was 37.5% at 4 years, confirming the gravity of
dermatomyositis. Malignancy developed in 9 patients (28.1%) leading to death in
all cases, within 18 months in 8. Amyopathic dermatomyositis was observed in 2 of
these patients. Necrotic skin ulcerations (p < 0.01) and pruritus (p < 0.05) were
significant predictive factors for the development of cancer. Poor prognosis
factors were malignancy (p < 0.001), necrotic skin ulcerations (p < 0.01), and
pruritus (p < 0.05). CONCLUSION: Prognosis is poor in certain sub-groups of
patients with dermatomyositis. Such patients can be identified on the basis of
skin lesions, notable necrotic ulcerations.
PMID- 9636750
TI - [Atrophic collodion-like skin in long-term treatments with hydroxyurea].
AB - INTRODUCTION: Despite good general and hematological tolerance, hydroxyurea
frequently causes polymorphous skin lesions when given as long-term therapy.
Distal skin atrophy, pseudodermatomyositis, pseudolichen and ulcerations have
been observed. CASE REPORT: We report three cases of diffuse atrophic collodion
skin in patients given long-term hydroxyurea. Histology findings demonstrated
atrophy and the same signs located at the dermo-epidermal junction as seen in
acute toxidermia due to hydroxyurea. Examination of the ultrastructure showed
abnormalities in the proliferative epidermal layer which was disrupted by edema
and a multiple, irregular basal membrane. DISCUSSION: The chronology of the
lesions and partial resolution after treatment withdrawal together with clinical
and histological signs demonstrating hydroxyurea impregnation would implicate
hydroxyurea as the cause of this case of diffuse atrophic collodion skin. Cells
in the epidermal layer of the skin, the most external layer in the organism, have
a high turnover rate and would be more vulnerable to the cytostatic action of
hydroxyurea than other tissues. The effect of hydroxyurea on keratinocytes
implicated in the production and maintenance of the basal membrane would be one
of the causes.
PMID- 9636751
TI - [Malignant syphilis in human immunodeficiency virus infection].
AB - INTRODUCTION: The associated infection with Treponema pallidum and human
immunodeficiency virus (HIV) was responsible for the return of malignant
syphilis. CASE REPORT: We report a case of malignant syphilis which revealed a
HIV seropositivity. The lesions were typical. Serological features were in
accordance with the diagnosis. A treatment with penicillin was prescribed and
there was no relapse after five years. DISCUSSION: The diagnosis of malignant
syphilis in a HIV positive patient may be difficult. The course of the disease
may be serious and a prolonged treatment with high doses of penicillin is often
necessary. The occurrence of the malignant syphilis in HIV positive patients is
not fortuitous and seems to be related to an abnormal immunity.
PMID- 9636752
TI - [Ulcers of the tongue, pityriasis lichenoides and primary parvovirus B19
infection].
AB - INTRODUCTION: We report a case of parapsoriasis en gouttes (or pityriasis
lichenoides) which presents two peculiarities. First, the patient had lingual
ulcerations and second, the eruption appeared during a seroconversion for
Parvovirus B19. OBSERVATION: A 25 old woman presented a first episode of
characteristic parapsoriasis en gouttes associated with purpuric palmoplantar
lesions and lingual ulcerations, reaching deep muscular in histology. DISCUSSION:
This observation of parapsoriasis en gouttes, peculiar because of lingual
ulcerations, is mostly interesting because of its association with a primo
infection to Parvovirus B19. The receptor of the virus is localised on
endothelial cells and that could explain purpuric lesions and ulcerations
observed.
PMID- 9636753
TI - [Cowden disease: treatment with acitretine].
AB - INTRODUCTION: Cowden's disease is a rare hereditary skin disease which is
important to recognize due to the risk of cancer. CASE REPORT: A 40-year-old man
was hospitalized for psoriasis. He presented florid papillomatous lesions
involving the lip and the buccal cavity, a thyroid adenoma and polyposis of the
gut. The diagnosis of Cowden's disease was retained. Treatment with acitretin,
0.75 mg/kg/d was initiated for the psoriatic lesions. Hypertrophic lesions of the
lip and mouth regressed during treatment but reappeared when the drug dose was
tapered of then withdrawn. The course of the polyposis was not verified.
DISCUSSION: This case demonstrates the frequency of digestive tract involvement
in Cowden's disease and the favorable, though transient, effect of oral retinoids
on mucosal lesions in Cowden's disease.
PMID- 9636754
TI - [Perforating necrobiosis lipoidica: 2 cases].
AB - INTRODUCTION: Perforating necrobiosis lipoidica is a rare clinical form of
necrobiosis lipoidica and is almost always associated with diabetes. Necrotized
tissue is usually eliminated via transfollicular perforations. CASE REPORT: We
report two cases of perforating necrobiosis lipoidica associated with type II
diabetes mellitus. The characteristic clinical feature was the presence of
keratotic plugs around the periphery of the lesions. Transfollicular perforation
predominated in the first case. The second also presented epidermal perforation.
DISCUSSION: There have been only 6 cases of perforating necrobiosis lipoidica in
the literature. To our knowledge, this is the first case report of transepidermal
elimination. We confirmed the constant association between this perforation type
and diabetes mellitus.
PMID- 9636755
TI - [A case for diagnosis: tuffed hair folliculitis].
PMID- 9636756
TI - [A case for diagnosis: infantile digital fibromatosis].
PMID- 9636757
TI - [Prurigo strophulus: cutaneous manifestation of hypersensitivity to environmental
arthropods].
PMID- 9636758
TI - [Bartonella infections].
PMID- 9636759
TI - [Question of the month: should dermatologic check-up be done?].
PMID- 9636760
TI - [What is a Caucasian?].
PMID- 9636761
TI - [Melanoma in Togo. A retrospective study over 20 years].
AB - INTRODUCTION: The malignant melanoma is a rare malignant tumour in black
patients, but it is common in white patients. MATERIAL AND METHODS: Medical
records were reviewed retrospectively during 20 years (1973-1992) to determine
the epidemiological features of malignant melanoma in Togo. RESULTS: During this
period 63 cases (31 males and 32 females) of malignant melanoma were
histologically diagnosed; an average of 3.15 cases each year. The tumor takes
place preferably on the feet 40 cases (63.49%), hands 15 cases (19.04%), legs and
thigh 10 cases (15.87%). CONCLUSION: The results of this study confirm the
particularity of malignant melanoma in black subjects: its rarity and the feet
localizations.
PMID- 9636762
TI - [Cutaneous immature hemangioma and hepatic angioma: there is no frequent
association].
AB - INTRODUCTION: The aim of this work was to determine the usefulness of systematic
liver sonography in patients with immature cutaneous hemangiomas. PATIENTS AND
METHODS: Children with immature cutaneous hemangiomas who met inclusion criteria
underwent liver sonography. RESULTS: No case of hepatic angioma was observed.
CONCLUSIONS: Liver sonography is not necessary as a routine test in children with
several immature angiomas. This examination could be proposed in situations other
than those evaluated in this work including miliary angiomas, unusual immature
angiomas, hepatomegaly, unexplained heart failure.
PMID- 9636763
TI - [Treatment of keloid with intralesional bleomycin].
AB - INTRODUCTION: Treatment of keloids is often disappointing and sometime quite
difficult to manage. In addition to unpleasant esthetic effects, treatment may
also produce functional impairment due to pruritus and contraction of the scar
tissue. PATIENTS AND METHODS: We proposed a new treatment scheme using
intralesional infiltrations of bleomycin. RESULTS: We treated 31 keloids and 5
hypertrophic scars with 3 to 5 infiltrations with a 1-month period. Total
regression was obtained in 25 keloids and hypertrophic scars. Important
regression was obtained in 6 keloids (86% good results). Treatment was effective
in all cases within the first 2 infiltrations evidenced by a reduction in the
volume of the keloid and clear reduction of functional impairment in most
patients. CONCLUSION: Effective well-tolerated treatment without pain was
achieved with infiltration suggesting that this treatment should be used as first
line therapy for keloids.
PMID- 9636764
TI - [Abnormal central nervous conduction in long-term treatments with retinoids].
AB - INTRODUCTION: Neurological manifestations are uncommon among the undesirable
effects of systemic retinoid therapy. We observed a case of axial rigidity
imputable to acitretine. Somesthesic evoked potentials were also altered. We
therefore searched for such abnormal findings in patients given long-term
systemic retinoid therapy. PATIENTS AND METHODS: A neurological exploration was
performed in two groups of patients, G1 and G2, with psoriasis and no
neurological complaint. The exploration included a physical examination, a study
of the somesthesic evoked potentials of all 4 limbs and an electromyogram in case
of abnormal findings. There were 8 patients (3 women, 5 men, mean age 56 years,
age range 39-71) in G1 treated with systemic retinoids for a mean 140 months (80
185). Cumulative dose was 50 to 280 g with a daily dose of 0.2 to 0.6 mg/kg/day,
i.e 20 to 50 mg/d of etretinate or acitretine. In G2, there were 5 subjects (mean
age 42 years, range 21-52) with psoriasis (mean duration 20 years range 14-25)
who had never been treated with systemic retinoids. RESULTS: Alterations in
somesthesic evoked potentials were observed in 7 of the 8 patients in G1.
Bilateral disturbances were seen in 6 cases, demonstrating abnormal lemniscal
central nervous conduction in the dorsal and/or cervical level in 3 cases and the
cervical level alone in 3 cases. There was one asymmetrical case involving the
lumbar level on the right and the dorsal and/or cervical level on the right. Only
one of the 5 controls in G2 had a minimal unilateral reduction in somesthesic
evoked potentials involving the lower limb. Direct effect of systemic retinoids
was retained in absence of any other cause due to metabolic, toxic or deficient
disorders or spinal compression. CONCLUSION: Long-term use of systemic retinoids
induces frequent latent neurological anomalies expressed as lemniscal central
nervous conduction. It is hypothesized that pathogenesis involves changes in the
lipid composition of the nervous membranes.
PMID- 9636765
TI - [Anetoderma during antiphospholipid syndrome. 3 cases].
AB - INTRODUCTION: Anetoderma is a skin disease of unknown etiology sometimes
encountered in patients with a lupus syndrome. We report a clinical and pathology
analysis of 3 selected cases of anetoderma associated with systemic lupus
erythematosus and/or antiphospholipid syndrome. CASE REPORTS: Three patients had
skin lesions typical of anetoderma. Antiphospholipid antibodies were present in
all three (anticardiolipin in 3, circulating lupus anticoagulants in 3, anti-beta
2GP1 in 2). One patient with systemic lupus erythematosus had signs of
antiphospholipid syndrome, the two others had primary antiphospholipid syndrome.
DISCUSSION: The analysis of our cases and a review of the literature suggest that
anetoderma is a disease which develops in the immunological environment of lupus,
and is apparently more related to the presence of antiphospholipids than lupus
itself. Thus anetoderma could be another cutaneous sign of the antiphospholipid
syndrome.
PMID- 9636766
TI - [Acute necrotizing cutaneous streptococcal infection following bites or scratch
by dog or cat].
AB - INTRODUCTION: Domestic animal bites or scratches are quite frequent. Among banal
bacteria isolated from infected bites or scratches, group A streptococcus seems
to be frequently associated with severe infections. CASE REPORTS: Three cases of
acute necrotizing cutaneous streptococcal infections, following cat or dog bite
or scratch are reported. Twice, group A streptococcus was isolated from cutaneous
swabs. In the third case, previous antibiotic therapy had sterilised
bacteriological samples. Diagnosis was ascertained on the basis of clinical
presentation and significant antistreptococcal antibodies elevation. Skin
necrosis around the inoculation area was observed in the 3 cases. Cicatrisation
required an average of two months under appropriate treatment. DISCUSSION: An
evolution towards cutaneous necrosis localized to the initially injured area is
common to these three cases. This peculiar evolution is worth to be known in
order to choose an effective anti streptococcal antibiotherapy whenever domestic
animals bites and scratches are to be treated.
PMID- 9636767
TI - [Giant congenital blue nevus of the scalp].
AB - INTRODUCTION: Blue nevi are small acquired melanocytic tumors. Two clinical forms
are described, a fibrous form and a cellular form. Giant nevi are exceptional.
CASE REPORT: We describe a patient with a giant blue nevus of the scalp. In
addition to this congenital, noninvasive tumor the patient presented numerous
cutaneous melanocytic nevi. The main lesion was removed by surgical exeresis
followed later with reconstruction plasty. The histological examination of the
surgical specimen showed an infiltrating blue cell nevi. After a 4-year follow
up, there has been no recurrence and no metastasis. DISCUSSION: There have been
11 cases of giant blue nevi reported in the literature. All were congenital
lesions with polymorphous clinical and histological aspects. Fibrous forms are
noninvasive and cellular forms have a potential for local invasion, whether
shortly after birth or later with invasion of muscles, bone and meninges without
intracerebral extension. Congenital blue nevi require early surgical exeresis.
PMID- 9636768
TI - [Follicular basaloid hamartoma localized in the sacral region with papular plaque
type].
AB - INTRODUCTION: Basaloid follicular hamartoma is a benign tumor with superficial
dermal proliferation of thin basaloid cords in a fibrous stroma. CASE REPORT: A
congenital case with sacral plaque-like papules is described. DISCUSSION: Three
different forms have been reported: a solitary form (usually an alopecic scalp
plaque), a generalized acquired form associated with myasthenia, and a linear
form. Histological diagnosis may be difficult and require clinico-pathological
evaluation.
PMID- 9636769
TI - [Benign symmetrical lipomatosis of the tongue].
AB - INTRODUCTION: Lipomatosis of the tongue is rarely observed. CASE REPORT: An 85
year-old man with chronic alcoholism presented several symmetrical lipomas of the
tongue with no other clinical manifestations. There was no capsule at the
histology examination. DISCUSSION: The multiple and symmetrical nature of the
lesion without a capsule led to the diagnosis of benign symmetrical lipomatosis
of the tongue, the fourth case reported in the literature.
PMID- 9636770
TI - [Acne induced by amineptin: adnexal toxiderma].
AB - INTRODUCTION: Amineptine-induced acne is a classical side effect often
encountered after prolonged and excessive use of the antidepressor. CASE REPORT:
We report the case of a young female drug addict (benzodiazepines and alcohol)
who denied overuse of amineptine. The initial inflammatory aspect of the lesion
was unusual as was the histology report. The sebaceous glands were the site of
cystic dilatation as would be expected, but in addition the sudoriparous glands
showed keratinizing syringometaplasia with areas of neutrophilic eccrine
hidradenitis. DISCUSSION: This is the second report of such a case similar to
other due to chemotherapy, benaxoprofene or toxic agents for example, and
corresponds to direct toxicity to the sudoriparous glands which accumulate
amineptine. We therefore propose the term of adnexal toxic drug eruption.
PMID- 9636771
TI - [Cutaneous manifestations of acromegaly: 4 cases].
AB - INTRODUCTION: Some skin changes in acromegaly belong to the classical dysmorphic
syndrome. Furthermore, other minor skin changes can be associated. OBSERVATIONS:
We report 3 patients consulting in the department of Dermatology for various skin
changes that have lead to the diagnosis of acromegaly. However these patients
have also typical dysmorphic syndrome that they have failed to recognize. The
fourth patient associated a cutaneous mastocytosis and acromegaly, as reported
only once in literature. The evolution of the minor skin changes was parallel
with the endocrinopathy. Moreover in one case, they have preceded the recurrence
of the acromegaly. COMMENTS: Our observations demonstrate the importance of the
minor skin changes that lead the patient to consult more than the dysmorphic
syndrome. Moreover these changes that depend of growth hormone and other
associated growth factors can be evolutive signs for endocrinopathy.
PMID- 9636772
TI - [Recurrent phototriggered summer light eruption of the axillary and inguinal
area: an atypical topographic form of benign summer lucitis].
AB - INTRODUCTION This case report of benign summer light eruption emphasizes the
importance of phototests in the diagnosis of photosensitive dermatoses. CASE
REPORT: A 25-year-old man, phototype II, had experienced a pruriginous
papulovesicular erythematous eruption of the axillary and inguinal regions each
summer for 12 years. A high-dose UV phototest (40 J/cm2 x 3 days) directed on the
right posterior axillary area and a whole body exposure test (4 J/cm2 UVA, 20
mJ/cm2 UVB x 3 days) were positive both clinically and histologically on day 4.
DEM B was normal at 26 mJ/cm2. Iterative polychromatic phototest (DEM x 3 days)
in the area usually involved (left posterior axillary region) was negative. The
simple UVA (13 J/cm2) and iterative phototests performed on the back were
negative. The results of the phototests led to the diagnosis of benign light
eruption despite the unusual localization. DISCUSSION: The diagnosis of benign
light eruption is generally clinical. Phototests are unnecessary in most cases.
Benign light eruption can be triggered by high-dose iterative UVA exposure of the
susceptible area or whole body phototests (UVA-UVB). These specific phototests
are indicated in atypical forms or localizations in order to determine the course
of benign light eruption and to uncover simulations.
PMID- 9636773
TI - [Type B Haemophilus influenzae cellulitis in an immunocompetent adult].
AB - INTRODUCTION: Only a few cases of Haemophilus influenzae type B cellulitis have
been reported in adult patients. They generally involve immunocompromised
patients, and are located in the cervico-facial areas. CASE-REPORT: We report a
43 year-old immunocompetent patient who presented a cellulitis of the leg. No
cutaneous or upper respiratory pathways entry portal was found. Abcedation of
cutaneous lesions allowed the isolation of numerous colonies of Haemophilus
influenzae type B from a subcutaneous fluid aspirate. COMMENTS: The unusual site
of the infection, the age and the immunocompetent status of the patient, the lack
of initial infectious localisation and the slow healing of lesions despite
appropriated antibiotic therapy, are of particular interest.
PMID- 9636774
TI - [Osteomalacia cured by resection of cutaneous neurinoma].
AB - INTRODUCTION: Regression of osteomalacia after exeresis of a skin tumor is
unusual. CASE REPORT: A 62-year-old man had suffered from bone and joint symptoms
for several years due to osteomalacia which was confirmed both biologically and
histologically. The patient also had a plantar neurinoma. After exeresis of the
tumor the biological results returned to normal levels within one week followed
by regression of the clinical signs of osteomalacia. DISCUSSION: The neurinoma in
this patient was apparently the cause of osteomalacia, since signs of the disease
disappeared after exeresis. To date, three cases of neurinoma associated with
osteomalacia have been published, including a single case with skin localization.
The tumor would secrete a substance which inhibits the synthesis of vitamin D and
enhances phosphorus excretion.
PMID- 9636775
TI - [Skin burns, necrosis and ulcers caused by wet cement, ready-mixed concrete and
lime. 8 cases].
AB - INTRODUCTION: Skin burns and caustic ulcers caused by wet cement, due to calcium
hydroxyde, are rarely reported in the literature. They occur mostly among amateur
cement users. OBSERVATIONS: We report seven cases of skin burns, necrosis and
ulcerations after use of wet cement and ready-mixed concrete, and one case of
caustic ulcers induced by wet lime. CONCLUSION: Even short skin contacts to wet
cement or concrete may induce extensive lesions in some cases. However, we were
not able to incriminate with certainty any special concrete additives which could
increase skin penetration of calcium hydroxyde. Warning notices about the danger
of skin contact should be prominent on sacked cement. When ready-mixed concrete
is delivered, the purchaser should be handed a note explaining the risk of
kneeling in wet concrete and the importance of protective measures. This may
probably contribute to reduce the frequency of those accidents.
PMID- 9636776
TI - [Shulman syndrome and anti-neutrophil cytoplasmic antibodies].
PMID- 9636777
TI - [Systemic treatment of psoriasis by fumaric acid derivatives].
PMID- 9636778
TI - [A case for diagnosis: follicular mucinosis].
PMID- 9636779
TI - [A case for diagnosis: multiple digital herpes].
PMID- 9636780
TI - [Cutaneous tumors and osteomalacia].
PMID- 9636781
TI - [Idiopathic CD4 lymphocytopenia].
PMID- 9636782
TI - [Diagnostic phototesting with UVA-UVB phototherapy unit: technical procedures,
liability].
PMID- 9636783
TI - [Question of the month. Is there any risk of prescribing methotrexate in
psoriasis, the use of which is not legally allowed in France?].
PMID- 9636784
TI - [Question of the month. What should be done with sexual partners?].
PMID- 9636785
TI - [Charles Rouet (1923-1996)].
PMID- 9636786
TI - [Erythropoietin in anesthesia and intensive care].
PMID- 9636787
TI - [Evaluation of cognitive functions after anesthesia with propofol].
AB - OBJECTIVES: To assess the disturbances and delay of recovery of cognitive
functions following propofol anaesthesia, and to evaluate a series of simple
cognitive recovery tests. STUDY DESIGN: Prospective comparative non randomized
clinical study. PATIENTS: Two groups of non premedicated patients, of ASA
physical class 1 and 2 were studied. The control group (n = 11) included patients
undergoing gastric fibroscopy under local anaesthesia. The propofol group (n =
22) consisted of patients scheduled for coloscopy under propofol anaesthesia.
METHODS: The gastric fibroscopy was performed under local anaesthesia with
lidocaine and the coloscopy under general anaesthesia with propofol as the sole
anaesthetic. Five cognitive tests, designed to assess short-term memory, delayed
memory, the ability to plan complex tasks, attention, and language comprehension
were conducted the day before, and 1 hour, 3 hours and 6 hours after the
endoscopy. RESULTS: The cognitive functions remained significantly depressed for
at least 3 hours after anaesthesia, and recovered fully about 6 hours after the
cessation of propofol administration. The capacity for planning was the most
heavily affected. CONCLUSIONS: Complete recovery can be evaluated by simple
cognitive tests, which showed that cognitive functions are impaired over a longer
period than psychomotor functions. Oral instructions may therefore not be fully
understood by the patient within 3 hours after anaesthesia, emphasizing the
importance of written instructions and the essential role played by a well
informed accompanying person.
PMID- 9636788
TI - [Evaluation of the blood quality collected by cell-saver during cesarean
section].
AB - OBJECTIVE: To determine the quality of blood salvaged and processed during
Caesarean section with a cell-saver. STUDY DESIGN: Laboratory study. PATIENTS:
The study included 20 patients of ASA physical class 1 or 2 undergoing a
scheduled Caesarean section. METHODS: A separate suction device was used from the
beginning surgery until the delivery of the fetus, to remove most of the amniotic
fluid coming from the surgical field. Thereafter using an Haemolite 2Plus
(Haemonetics), the blood was separated and washed with 2 L of normal saline
solution. Blood quality was assessed through detection of fetal cells and
measuring out of alpha-fetal-protein, tissue factor. A Kleihauer test was also
performed. RESULTS: Cell-saver processing removed most of alpha-fetal-protein and
tissue factor while fetal cells were rarely seen. The Kleihauer test could not be
performed because of haemolized blood samples. However, the results were very
heterogeneous and after washing some salvaged units contained very high
concentrations of alpha-fetal-protein or tissue factor. CONCLUSIONS: These
preliminary results show that intra-operative autologous transfusion is not fully
safe during Caesarean sections. In addition, there is an immunological risk if a
significant part of fetal red blood cells are reinfused into maternal
circulation. Therefore, additional studies are needed to better assess this risk.
PMID- 9636789
TI - [Influence of arteriovenous hemofiltration on teicoplanin pharmacokinetics].
AB - OBJECTIVE: To assess the pharmacokinetics of a single dose of teicoplanin in
critically ill patients treated with continuous arteriovenous haemofiltration
(CAVH). STUDY DESIGN: Prospective open clinical study. PATIENTS: Eleven patients
with acute renal insufficiency and suspected of a Gram negative infection.
METHOD: After injection of teicoplanin, 6 mg.kg-1 over 30 minutes the plasma and
haemofiltrate concentrations were measured over 24 hours with high power liquid
chromatography (HPLC). RESULTS: In plasma, the mean half-life of the first phase
was 0.6 +/- 0.2 hour and terminal half-life was 16.4 +/- 5 8 hours, total
clearance 30.4 +/- 7.1 mL.h-1.kg-1, volume of distribution was 0.7 +/- 0.3 L.kg-1
and the mean resident time 19.2 +/- 7.4 hours. In the haemofiltrate, the amount
of teicoplanin eliminated after 24 hours was less than 1% in seven patients,
between 1.8 and 3.7% in three and reached 7% in one patient. CONCLUSION: During
CAVH, the elimination of a single dose of teicoplanin in the haemofiltrate is
low.
PMID- 9636790
TI - [Hemodynamic changes induced by apnea test in patients with brain death].
AB - OBJECTIVE: In France, an apnoea test is compulsory to confirm brain death. This
test results in a major hypercarbia and respiratory acidosis. This study aimed to
assess haemodynamic changes elicited by the apnoea test. STUDY DESIGN:
Prospective clinical study. PATIENTS: Fifteen patients with brain death METHODS:
Before the apnoea test, the lungs were ventilated with pure oxygen for 20
minutes. Thereafter, the test was conducted with continuous oxygen flow through
the endotracheal tube, and SpO2 monitoring. Blood gases and haemodynamic
parameters, including systemic arterial pressure, pulmonary artery pressure,
pulmonary artery occlusion pressure, cardiac index and right ventricular function
parameters were assessed before, during and 20 minutes after the apnoea test.
Mean values at the various times were compared. RESULTS: Hypercarbia and acidosis
induced a major pulmonary hypertension and an increase in cardiac output,
associated with a decrease in systemic vascular resistances. Despite pulmonary
hypertension and acidosis, right ventricular function was maintained. All
haemodynamic modifications were reversed by reventilation. CONCLUSION: Apnoea
test induces a reversible pulmonary hypertension that is seemingly not
deleterious for right ventricular function. Apnoea test probably does not alter
viability of the donor's organs.
PMID- 9636791
TI - [Diagnostic characteristics of acquired pneumonia in patients under mechanical
respiration].
AB - Ventilator-associated pneumonias (VAP) are the most frequent nosocomial lung
infections. Histological diagnosis is the standard for reference. A diagnosis of
VAP can be considered in presence of fever or hypothermia, hyperleucocytosis or
leucopenia, worsening of blood gases, and new radiological infiltrate. Their
diagnostical value is dependent on the number of included manifestations. A
clinical pulmonary infection score (CPIS) has been produced and compared with
histological data. Bacteriological data are essential for an adapted
antibiotherapy. The blind non-protected specimen brush is inexpensive and
reliable at levels of 10(4) and 10(6) CFU.mL-1, the sensitivity and specificity
reach 60%. The double-protected catheter is a sensitive and specific test at the
level of 10(3) CFU.mL-1. At present its accuracy has only been compared with
bronchial brushing. The culture of a 20 mL mini-broncho-alveolar lavage (same
material) is specific (50%) but not sensitive enough (< 70%) at the level of
10(3) CFU.mL-1. The culture of the protected telescopic brush is the most
expensive test. It does not carry a risk of contamination, but does not detect a
significant amount of VAP even at a level below 10(3) CFU.mL-1. Due to its high
specificity it is used as the reference test in numerous studies. The endoscopic
broncho-alveolar lavage provides a rapid diagnosis. Although not protected, it
carries a low risk of false positives. It also allows the diagnosis of non
bacterial or atypical bacterial lung infections. The diagnosis can also be
obtained with lung biopsy which however carries a risk in case of mechanical
ventilation, whatever the technique. Except for the protected double catheter, a
direct examination has been advocated, for the differentiation between infection
and colonization and the improvement of the performances of the simple culture of
the broncho-alveolar lavage (search for intra-cellular bacteria).
PMID- 9636792
TI - [Localized rhabdomyolysis after anaphylactic shock caused by suxamethonium].
AB - A young woman without remarkable medical history, experienced a life threatening
anaphylactoid reaction after induction of general anaesthesia for an emergency
curettage. Hypersensitivity reaction involving IgE antibodies against
suxamethonium was proven by positive skin test and detection of specific IgE by
radio-immuno assay. After intensive therapy for 2 to 3 hours, the patient
exhibited rhabdomyolysis localized on both calves. This complication, which
required fasciotomies, did not result in renal failure. Local and general outcome
was good. Rhabdomyolysis was due to compartmental ischaemia following shock and
local external compression in the lithotomy position.
PMID- 9636793
TI - [Does flumazenil correct disorders of intracardiac conduction induced by
accidental intravenous injection of bupivacaine?].
AB - The authors report the case of a patient who experienced intracardiac conduction
disturbances from accidental intravenous injection of bupivacaine, which were
reversed by an intravenous injection of flumazenil. Flumazenil could act either
in displacing bupivacaine from its binding site, or by an interaction involving
the GABAergic system, unless a specific interaction between flumazenil and
bupivacaine does exist. In case of experimental confirmation of this feature,
flumazenil could be proposed as a new therapeutic tool for bupivacaine-induced
cardiotoxicity.
PMID- 9636794
TI - [Treatment of post-traumatic acute anemia by recombinant human erythropoietin in
Jehovah's Witnesses].
AB - A 20-year-old Jehovah's witness patient experienced a femur fracture, with a
section of the femoral artery and vein. On admission, haemoglobin concentration
was 5.6 g.dL-1 and haematocrit 17%. Because of aponevrotomy, blood losses
persisted. As the patient refused blood transfusion, recombinant human
erythropoietin and parenteral iron were administered, associated with mild
hypothermia, sedation and mechanical ventilation. After 21 days, the haemoglobin
concentration increased to 10.9 g.dL-1 and haematocrit to 33% Recombinant human
erythropoietin and parenteral iron may provide an alternative safe and effective
therapy in life-threatening anaemia when blood transfusions are not accepted by
the patient.
PMID- 9636795
TI - [Acute respiratory distress syndrome and pancytopenia during miliary tuberculosis
in a HIV positive patient].
AB - Acute respiratory distress syndrome (ARDS) is a rare but severe complication of
miliary tuberculosis, which may occur even under antituberculous therapy. Even
with adequate treatment, its mortality is close to 70%, and if associated with
pancytopenia, it may reach 100%. Underlying diseases, delayed diagnosis and
additional complications are factors of poor prognosis. We report a case of a
patient infected with the human immunodeficiency virus who experienced
pancytopenia and ARDS associated with miliary tuberculosis. The patient recovered
under antituberculous chemotherapy.
PMID- 9636796
TI - [Factor XI deficiency, a new way of substitution: human purified concentrates].
AB - Case report of a 26-year-old patient, admitted for severe craniofacial trauma,
with facial injuries and intracranial haemorrhage. Preoperative tests showed an
aPTT = 64 s (control = 29 s), rapidly recognized as being caused by a major
constitutional factor XI deficiency (0.06 Ul.mL-1). Considering the neurological
risk and the indication for surgery, concentrates of factor XI were administered
at a dosage of 25 Ul.kg-1. This treatment was associated with a biological
normalization and uneventful surgery. In patients experiencing a factor XI
deficiency, the use of fresh frozen plasma will probably decrease and only
administered in emergency cases when factor XI concentrates are not available.
PMID- 9636797
TI - [Substances responsible for peranesthetic anaphylactic shock. A third French
multicenter study (1992-94)].
AB - Since 1989, the epidemiological survey of anaphylactoid reactions occurring
during anaesthesia is obtained in France with repeated inquiries by the
Perioperative Anaphylactic Reactions Study Group. The members of this group
collect during the study period the cases of patients having suffered from an
anaphylactoid reaction and tested in their allergo-anaesthetic outpatient clinic,
their characteristics (age, gender), the results of the allergological tests
(mechanism, agents responsible for the reactions). The two previous surveys
published in the Annales francaises d'anesthesie et de reanimation in 1990 and
1993 included 1,240 and 1,585 patients respectively. The current survey concerned
1,750 patients tested in 27 diagnostic centres, from January 1992 to June 1994.
The reactions occurred at all ages, predominantly between 10 and 50 years, the
sex-ratio (F/M) was 2.4. Allergological tests carried out to diagnose an immune
mechanism for the shock were cutaneous tests in all centres (prick-tests in 21
centres, intradermal tests in 27 centres) using the same dilutions for the tested
agents and the same threshold for positivity. Specific IgE antibodies against
muscle relaxants, thiopentone and propofol, were measured by radio immunoassays
in 20 centres. The leucocyte histamine release test was used in 10 centres. The
immune origin of the shock--IgE dependent anaphylaxis--was diagnosed in 1,000
patients (57.8%) and due to 1,030 agents muscle relaxants (59.2%), latex (19%),
hypnotics (5.9%), benzodiazepines (2.1%), opioids (3.5%), plasma substitutes
(5%), antibiotics (3.1%) and other drugs given during anaesthesia such as
aprotinine and protamine (2.2%). Suxamethonium was responsible for 39.3% of
muscle relaxant anaphylaxis, vecuronium for 36%, atracurium for 14.5%,
pancuronium for 4.8%, gallamine for 3.1% and alcuronium for 2.3%. The latter has
been withdrawn from the French market in 1993. These differences in the incidence
of reactions are correlated with the clinical use of muscle relaxants in France
for vecuronium and atracurium, however not for suxamethonium, responsible for 39%
of the reactions but representing only 5% of the muscle relaxants sold in France.
The comparison with the two previous surveys confirms that the mechanism of more
than half of the anaphylactoid reactions occurring during anaesthesia is of
immune origin, due to specific IgE antibodies. It is therefore essential to
systematically carry out an allergologic assessment several weeks after the
reaction, in order to discard for the subsequent anaesthetics the agent(s)
responsible for anaphylaxis. If the muscle relaxants remain the first drugs
involved in shock occurring at induction, there is a significant increase in
latex shock, as demonstrated by the three epidemiological surveys (0.5%, 12.5%
and now 19%). The incidence of other anaesthetic agents, antibiotics and plasma
substitutes remains unchanged.
PMID- 9636798
TI - [Blood transfusion in surgery: can it still be reduced by human recombinant
erythropoietin?].
AB - New agents such as recombinant human erythropoietin (rHu EPO) modify conventional
transfusionnal strategies. For accurate indications, such as, anaemia associated
with chronic renal failure, cancer or cardiac disease, the preoperative
prescription of rHu EPO may reduce transfusion requirements. rHu EPO may also be
associated with pre-deposit transfusion in patients with anaemia before blood
donation, when the transfusion needs are high, or the period for blood pre
deposit donation shortened. Postoperatively rHu EPO is only efficient if it is
administered for a prolonged period; this condition limits its indications and
value because of its high cost.
PMID- 9636799
TI - [A new device for free airway maintenance during anesthesia: cuffed oropharyngeal
airway].
PMID- 9636800
TI - [Ketoacidotic coma, a way to discover severe acute pancreatitis in a non-diabetic
patient treated with acitretin].
PMID- 9636801
TI - [Anesthetic drugs available for mobile health unit physicians in France].
PMID- 9636802
TI - [Foreign body in the pharynx during intubation].
PMID- 9636803
TI - [Legionellosis and enteritis].
PMID- 9636804
TI - Immunotherapy as an effective tool in allergy treatment.
PMID- 9636805
TI - Risk and safety of immunotherapy.
AB - The risk and safety of specific immunotherapy (SIT) has been the subject of many
well-designed studies since it was introduced. Most authors consider SIT an
efficient and safe mode of treatment despite the occurrence of life-threatening
anaphylactic reactions. They emphasize the importance of a proper selection of
patients as well as the requirement for highly qualified physicians to provide
the treatment. Another problem associated with the safety of SIT is the potential
enhancement of the synthesis of immune complexes after the treatment. SIT causes
a decrease in allergen-specific IgE which is slower in circulating immune
complexes than in the serum. No data are available to show that SIT induces
immune-complex diseases, in either the immunologic or the clinical sense. As far
as anaphylactic reactions are concerned, new alternative methods different from
the conventional parenteral mode of delivery seem to be safe. Our increased
understanding of the altered functions of the immune system justifies the
assumption that the more specific the method of SIT administration, the more
effective and safe it is.
PMID- 9636806
TI - Local immunotherapy: pharmacokinetics and efficacy.
PMID- 9636807
TI - Mechanisms of specific immunotherapy of allergic diseases.
PMID- 9636808
TI - Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo
controlled trial of a standardized five-grass-pollen extract in rhinitis.
AB - Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen
extracts has been found to be effective in reducing allergic symptoms and
medication needs. A double-blind, placebo-controlled study was carried out in a
large number of patients to determine whether medication needs can be reduced by
SLIT. Some 136 patients with grass-pollen rhinitis with or without mild asthma
were studied. Patients received either placebo or SLIT with a standardized grass
pollen extract administered daily with increasing doses up to 300 IR (index of
reactivity) from January to the end of July 1994. During the grass-pollen season,
patients were instructed to use medications as required and to visit their
doctors in case of asthma. Symptom-medications scores were assessed during the
pollen season, and serum-specific IgG4 was measured before and at the end of
SLIT. In the SLIT group, drug consumption dropped significantly throughout the
pollen season (P < 0.02). Moreover, at the peak of the pollen season,
betamethasone consumption was significantly reduced in the SLIT group (P < 0.02).
Only one patient in the SLIT group had an asthma attack compared to eight
patients in the placebo group (P < 0.02). IgG4 levels increased significantly in
the SLIT group (P < 0.001) but without correlation with symptoms. Side-effects
were comparable in both groups. This study indicates that SLIT in grass-pollen
rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug
consumption and the need for oral corticosteroids.
PMID- 9636809
TI - Guanine, mite, and cockroach allergens in Costa Rican homes.
AB - Previous studies of schoolchildren in Costa Rica have shown an asthma prevalence
of 23% and a high level of sensitization, particularly to mite allergens. As a
continuation of these studies, some 400 dust samples were collected from various
places in Costa Rica, and parts of these were analyzed for specific mite and
cockroach allergens, as well as for the number of mites and amount of guanine.
Guanine was quantified by a diazo, as well as an HPLC method, which were found to
be highly correlated. The concentrations of guanine by the diazo method, Der p 1,
Der f 1, and the number of mites were higher in bed dust than in bedroom floor
dust, and it was possible to quantify mite allergens and guanine in almost all
bed-dust samples. The mean levels were 2-3 times higher than the proposed risk
level for elicitation of symptoms in mite-sensitive asthmatics. Bed and bedroom
floor dust contained more guanine and mite allergen in humid (> 2000 mm rain)
than in drier places (P < 0.05), but the number of mites in bed and bedroom floor
dust was higher in less humid places (P = 0.01). The guanine content in bedroom
floor dust was higher in areas with a temperate climate than in areas with a
warmer climate (P < 0.001, Bartlett's chi square [BCS]), as was the number of
mites (P < 0.01, Kruskal-Wallis [KW], 0.04, BCS) and the Der p 1 concentration (P
= 0.01, BCS; P = 0.02, KW). The Der f 1 concentration in bedroom floor dust was
higher in a warmer than in a temperate climate (P < 0.001, BCS). More guanine and
mites were found in urban than in rural bed dust (P = 0.03, KW). Dust samples
from the metropolitan area (temperate climate) of Costa Rica contained higher
levels of guanine (P < 0.01) and Der p 1 (P = 0.07) than the coastal areas, but
very little Der f 1. In these samples, guanine and Der p 1 allergen were closely
related, and 2 micrograms of the allergen was equivalent to 0.49 mg of guanine.
Two-thirds of bed and floor samples collected on cotton filters contained Bla g 2
allergen at mean levels of 1.6 and 2.1 units/g dust, respectively. Cockroach
allergen was, however, absent in all bed samples from the metropolitan area, but
did occur in very high concentrations in the coastal bed dust samples collected
with tighter polyester filters. In conclusion, the concentration of guanine and
Der p 1 was very high in the bed dust of Costa Rican homes. Some factors, such as
humidity, small houses for large families, and type of bedding, probably favored
the heavy mite infestation, which is probably related to the widespread
occurrence of bronchial asthma in this country.
PMID- 9636810
TI - IgE, IgA, and IgG responses to common yeasts in atopic patients.
AB - This study was undertaken to analyze the differences in exposure and
sensitization to five common environmental yeasts. The responses of IgG, IgA, and
IgE to Candida albicans, C. utilis, Cryptococcus albidus, Rhodotorula rubra, and
Saccharomyces cerevisiae and purified S. cerevisiae enolase were analyzed by
immunoblotting (IgE-IB), and the cross-reactivity of their IgE-binding components
by IgE-IB inhibition. Twenty atopic subjects, with asthma, allergic rhinitis, or
atopic dermatitis were included. In skin prick tests (SPT), 12 of the patients
showed simultaneous reactivity to at least two of the five yeasts, four reacted
to one of the yeasts, and four had no responses. Antigens run in SDS-PAGE and
transferred to nitrocellulose were probed with enzyme-labeled IgA-, IgG-, and IgE
specific antibodies. The IgE immunoblotting revealed most IgE-binding bands in C.
albicans (11 bands) followed by C. utilis (eight bands), S. cerevisiae (five
bands), R. rubra (five bands), and Cr. albidus (four bands). Six of the IgE
binding bands of C. albicans and C. utilis shared molecular weight, and only two
bands shared molecular weight with other yeasts. These were the 46-kDa band,
shared by all five yeasts, and a 13-kDa band shared by four yeasts. Prominent IgE
binding was seen to a 46-kDa band of C. albicans (seven patients), C. utilis
(five patients), and S. cerevisiae (one patient) and to corresponding weak bands
of Cr. albidus and R. rubra (one patient). The possible cross-reactivity of the
46-kDa band was analyzed by IgE-IB inhibition and densitometry, revealing clear
C. albicans inhibition of C. utilis (80%) and enolase (98%) (autoinhibition
100%). The strongest IgG responses were seen against S. cerevisiae and C.
albicans. The responses were mainly against mannans of C. albicans and S.
cerevisiae, suggesting that most of the exposure is to these yeasts. Yeasts with
different types of exposure, from saprophytic growth on human mucous membranes to
exposure by air and food, were shown to cross-react at the allergenic level.
Atopic patients primarily sensitized by C. albicans and S. cerevisiae may develop
allergic symptoms by exposure to other environmental yeasts due to cross-reacting
IgE antibodies.
PMID- 9636811
TI - Amino acid sequence similarity of Hev b 3 to two previously reported 27- and 23
kDa latex proteins allergenic to spina bifida patients.
AB - Separate studies have reported spina bifida patients to be especially allergic to
proteins of 27 and 23 kDa found in the serum of centrifuged natural rubber latex.
An insoluble latex protein located on the surface of small rubber particles, Hev
b 3, has similarly been found to be allergenic to spina bifida patients. In this
study, internal amino acid sequences of Hev b 3 showed similarity to the
published sequences for the 27- and 23-kDa latex proteins. The latter allergens
are hence identified as Hev b 3. Determination of the molecular weight of Hev b 3
revealed various species of 22-23 kDa. The consistent gaps of about 266 Da
observed between various forms of the intact protein suggest that the protein
undergoes post-translational modification. To determine whether Hev b 3 also
occurs in a soluble form in the latex serum, its presence in molecular-filtered
serum was checked by ELISA and Western blot. The results showed Hev b 3 to be
largely absent in the C-serum from fresh latex. The protein is therefore
insoluble in its native state. However, a small amount of the solubilized protein
was detected in ammonia-stabilized latex (commonly used in the manufacture of
latex products).
PMID- 9636812
TI - Olive-pollen profilin. Molecular and immunologic properties.
AB - Olive-pollen profilin has been isolated and characterized as a significant
allergen. Its molecular properties, such as a molecular mass of 15 kDa; amino
acid composition; and secondary repetitive structure percentages of 15% alpha
helix, 33% beta-strand, 20% beta-turn, and 32% random coil, have been determined.
Its allergenic capability, a recognition frequency estimated at 24% of olive
hypersensitive patients, and high cross-reactivity with all the pollen used have
been found. The presence of conformation epitopes in the olive profilin, as well
as a high structural and immunologic similarity to other pollen sources such as
birch and ash, can be established from these studies.
PMID- 9636813
TI - CD86 (B7-2) antigen on B cells from atopic patients shows selective, antigen
specific upregulation.
AB - To determine whether B7 signals are associated with atopic responses in man, we
assayed CD80 and CD86 expression on B cells and monocytes from atopic patients
and controls. Peripheral blood mononuclear cells from 10 patients with perennial
allergic rhinitis and from 10 normal subjects were cultured in the presence or
absence of house-dust-mite antigen, and B cells and monocytes were assayed for
expression of CD80 and CD86 by flow cytometry. CD86 on B cells was significantly
and selectively upregulated in all atopic subjects, but not in normal subjects,
whereas CD80 expression was not altered in B cells from the atopic subjects or
controls. In contrast, both CD80 and CD86 were upregulated in monocytes from the
atopic subjects as well as the controls. However, CD86 upregulation was
significantly higher in the atopic subjects than in controls. Our results seem to
suggest that selective upregulation of CD86 on B cells by a challenging antigen
may play a critical role in the development of Th2 cells in patients with atopic
disease.
PMID- 9636814
TI - Latex allergy in fruit-allergic patients.
AB - The purpose of this study was to investigate the prevalence of latex allergy in
fruit-allergic patients, and to assess its clinical significance. Fifty-seven
fruit-allergic patients and 50 non-fruit-allergic atopic patient controls were
studied. All patients were questioned about conventional immediate symptoms after
contact with latex products. Patients also underwent skin prick testing and
determination of specific serum IgE to latex, as well as a screening test for
environmental allergens. Immunologic latex sensitization occurred in 49/57
(85.9%) fruit-allergic patients, who showed a positive STP and/or CAP to latex,
but in only two controls (P < 0.001). Six out of 57 (10.5%) fruit-allergic
patients suffered from clinically relevant latex allergy. Symptoms included
contact urticaria, angioedema, conjunctivitis, generalized urticaria, and
moderate anaphylactic reactions. No control reported symptoms with latex products
(P = 0.052). In all patients, clinical symptoms to fruits preceded a history of
latex allergy. The fruits most associated were melon, peach, and banana. From our
data, we conclude that there is a potential for allergic reactions to latex in
patients with allergy to fruit. All patients with fruit allergy should be
screened for individual risk of latex allergy.
PMID- 9636815
TI - BCG vaccination does not seem to prevent atopy in children with atopic heredity.
PMID- 9636816
TI - Cross-reactivity between buckwheat and latex.
PMID- 9636817
TI - Allergy to mare's milk.
PMID- 9636818
TI - Occurrence of allergens in hospital premises.
PMID- 9636819
TI - Preoperative screening for general anesthesia.
PMID- 9636820
TI - Ascites in hereditary angioedema.
PMID- 9636822
TI - Your metered-dose inhaler will be changing.
PMID- 9636821
TI - Loratadine reduces the expression of ICAM-1.
PMID- 9636823
TI - Cost-effectiveness of interferon-alpha for chronic myeloid leukemia.
PMID- 9636824
TI - PET scanning in clinical oncology.
PMID- 9636825
TI - Predicting hematological toxicity (myelosuppression) of cytotoxic drug therapy
from in vitro tests.
AB - Several clinical oncology units are studying the roles of in vitro
hematotoxicology in phase I evaluations. At the same time, the European Center
for the Validation of Alternative Methods (ECVAM) is supporting a validation
study of the CFU-GM assay. It is important that these activities be coordinated
so that high performance, optimized technical protocols are used for prospective
and retrospective clinical evaluations. The EROTC, the NCI and ECVAM could
provide support for these coordinated efforts. There is an opportunity for
medical oncologists involved in early clinical trials to participate in the
evaluation of in vitro tests and their clinical application . Fundamental to
acceptance of these assays by oncologists and regulatory scientists, they must
predict clinical outcome for myelosuppressive agents and then improve phase I
design and performance. These achievements would justify more aggressive dose
escalation schemes using guidance from in vitro studies without compromising
patient safety. Success in predicting neutropenia might also stimulate the
research required to understand how to predict other hematologic toxicities, such
as a thrombocytopenia. The complexity of a validation study in hematotoxicology
is that it seeks to predict the level of exposure that causes neutropenia, in
contrast to other validation studies that have sought to classify a xenobiotic as
toxic or not. It may be that the clinical relevance of a new assay is not just a
yes-no answer. This important distinction came from the realization that the
xenobiotic tolerance in other organ systems of the body must be the same or
greater than marrow in order for myelosuppression to be a clinical consequence of
exposure. Pharmacological principles of system exposure and toxicity that are
integrated into the prediction model provide the links to clinical oncology. It
is also important to anticipate future applications of in vitro hematotoxicology.
If the maximum tolerated level of drug exposure for human hematopoietic cells can
be predicted, then in vitro hematotoxicology could play an important role in new
drug discovery. One concept involves screening for compounds that show efficacy
at the IC level that predicts maximum tolerated exposure levels in the human.
'Therapeutic index based' drug discovery has been applied to the tallimustine
family with some success.
PMID- 9636826
TI - Do specialists do it better? The impact of specialization on the processes and
outcomes of care for cancer patients.
AB - OBJECTIVE: To assess the impact of specialization on processes and outcomes of
care for cancer patients. DATA SOURCE: Papers published in English between 1980
and 1995 and identified through MEDLINE and Embase (MeSH terms: NEOPLASM
(exploded), and PHYSICIAN PRACTICE PATTERNS (or DECISION MAKING, ATTITUDE OF
HEALTH PERSONNEL, QUALITY OF HEALTH CARE, DELIVERY OF HEALTH CARE, HEALTH
EDUCATION or OUTCOME ASSESSMENT HEALTH CARE), or through the reference lists of
review articles. STUDY SELECTION: Studies providing information on the
association between quality of care indicators for cancer patients and
clinician/centre degree of specialization. A total of 47 papers concerning 46
empirical studies were considered. DATA EXTRACTION: For studies using process of
care indicators, the proportion of specific procedures performed by specialists
and non-specialists was abstracted. For studies using outcome indicators (e.g.,
mortality), the effect of specialization was quantified in terms of odds ratio
(OR) expressing relative reduction in risk of death. The quality of individual
studies using process or outcome indicators was assessed according to study
design, avoidance of selection bias in patient identification and data analysis,
degree of adjustment of the comparison between clinicians/centres with different
levels of specialization. DATA SYNTHESIS: Specialized centres/clinicians fared
better both when process and outcome indicators were used. While the former
varied widely in different studies and their clinical relevance was often
questionable, mortality was consistently lower when care was provided by
specialized centres/clinicians, with the effect size being greater in smaller
studies. For breast cancer, where all the studies were of sufficiently good
quality, a pooled estimate of the effect of specialization was performed which
showed that specialized cancer care was associated with an 18% (95% CI: 12%-23%)
reduction in mortality. CONCLUSIONS: Despite the fact that care provided by
specialized centres/clinicians appeared to be better both when assessed in
relation to process indicators and to mortality, this evidence should be
considered far from conclusive because of major methodological flaws in these
studies. Relative to current efforts to promote evidence-based policy-making,
this review underscores the limited capability of scientific information to
provide reliable guidelines for structuring better health care systems.
PMID- 9636827
TI - Searching the medical literature for the best evidence to solve clinical
questions.
PMID- 9636828
TI - Successful treatment with lamivudine for fulminant reactivated hepatitis B
infection following intensive therapy for high-grade non-Hodgkin's lymphoma.
AB - Chronic carriers of Hepatitis B virus (HBV) infection, who are treated for
malignant lymphoma, are at high risk of mortality from reactivated HBV infection.
We report a case of a 29-year-old male chronic HBV carrier who developed
fulminant reactivated HBV infection following intensive chemotherapy for stage
IVB large cell B-cell non-Hodgkin's lymphoma associated with extensive central
nervous system and bone marrow involvement. Prior to chemotherapy the patient had
normal liver function tests and was negative for HBV DNA by semiquantitative PCR
assay. Fulminant HBV reactivation was confirmed following clinical deterioration,
massive rises in hepatic transaminases (peak alanine aminotransferase = 2,850
U/l), liver biopsy and rising levels of serum HBV DNA. Following treatment with
lamivudine 150 mg bd for 18 weeks dramatic and sustained recovery ensued.
Symptoms and liver function tests improved within days and HBV DNA became
negative within 12 weeks. Our patient later died from relapsed lymphoma but
without evidence of reactivated HBV infection. We advise that lamivudine should
be considered during intensive chemotherapy treatment of chronic carriers of HBV.
PMID- 9636829
TI - Cost-effectiveness of interferon in chronic myeloid leukaemia: analysis of four
clinical studies.
AB - BACKGROUND: Analysis of published survival curves can be used as the basis for
incremental cost-effectiveness analyses in which two treatments are compared with
one another in terms of cost per life-year saved. In patients with chronic
myeloid leukaemia in chronic phase, long-term treatment with alpha-interferon has
been reported to improve survival in comparison with standard treatments with
cytotoxic drugs. To assess the pharmacoeconomic profile of interferon treatment
in terms of cost per life-year gained, we conducted an incremental cost
effectiveness analysis. PATIENTS AND METHODS: The clinical material utilised in
our analysis derived from four published randomised trials comparing interferon
vs. busulphan or hydroxyurea. The Gompertz model was used to estimate the total
lifetime values of patient-years of subjects receiving interferon in comparison
with subjects given a standard cytotoxic treatment. RESULTS: Our primary analysis
showed that maintenance treatment with interferon improved survival expectancy by
37 to 93 discounted years for every 100 patients. The incremental cost
effectiveness ratio of interferon vs. cytotoxic therapy ranged from $93,000 to
$226,000 per life-year gained (discounted costs per discounted years). A
secondary analysis showed that the dose of interferon had significant influence
on the cost-effectiveness ratio. Because our literature search identified a fifth
study that showed an extremely favourable outcome using interferon but that was
not included in our primary analysis due to its design, we conducted another
secondary analysis based on these five studies that, however, confirmed the
results of the primary analysis. CONCLUSIONS: Our study indicates that an
unselected long-term treatment with interferon implies an unfavourable cost
effectiveness ranking in comparison with data of cost per life-year gained which
had previously been obtained from other types of medical intervention.
PMID- 9636830
TI - Clinical evaluation of whole-body 18F-fluorodeoxyglucose positron emission
tomography in the detection of liver metastases.
AB - BACKGROUND: Assessment of metastatic involvement of the liver remains a
diagnostic challenge. The objective of this study was to evaluate the potential
role of FDG PET in the detection of liver metastases. PATIENTS AND METHODS: Sixty
four patients with malignancy and possible liver involvement were included. Liver
metastases were present in 31 cases, demonstrated by histopathological analysis
in 15 cases and by follow-up in 16 cases. The negative cases were confirmed by
pathology in four cases, peroperative ultrasonography in 12 cases, and follow-up
in 17 cases. Whole-body FDG PET was compared to CT (n = 53) and US (n = 43).
RESULTS: PET demonstrated a 97% sensitivity, an 88% specificity and a 92%
accuracy, compared to 93%, 75% and 85%, respectively, for CT (P = NS). Concordant
results were obtained in 44 of 64 patients (69%: 19 TP. 25 TN). PET provided new
and accurate information in 15 of 64 patients (23.4%). PET demonstrated liver
metastases in 11 patients in whom conventional methods yielded negative (two
cases) or doubtful (nine cases) results. Four patients free of liver involvement
were correctly staged with PET, while CT/US were equivocal. PET was erroneous in
five of 64 cases (7.8%, four FP, one FN). CONCLUSIONS: FDG PET allows an accurate
screening of liver involvement in patients with malignancy. Combined with CT, it
provides additional diagnostic information that could directly affect the
management of these patients.
PMID- 9636831
TI - Dosage of adjuvant G-CSF (filgrastim)-supported FEC polychemotherapy based on
equivalent haematological toxicity in high-risk breast cancer patients.
Scandinavian Breast Group, Study SBG 9401.
AB - BACKGROUND: Conventional dosages of cytostatics in mg/m2 will cause marked
variations in systemic exposure, resulting in over- and under-treatment, at least
with respect to side effects. PATIENTS AND METHODS: We are conducting a
randomized adjuvant study for breast cancer patients younger than 60 years of age
with > or = 70% risk of recurrence within five years. The first 89 consecutive
patients who have received nine courses q three weeks of individually dose
escalated and G-CSF (filgrastim)-supported FEC (5-fluorouracil (5-FU),
epirubicin, and cyclophosphamide) therapy given with ciprofloxacin prophylaxis
were included in this analysis. Six different FEC dose levels were used for
treatment at equivalent haematological toxicity. Dose modifications were based on
white blood cell and platelet counts on days 8, 11/12, 15, and 22. RESULTS:
Eighty-three of 89 patients completed all nine courses. The median epirubicin and
cyclophosphamide doses were 782 mg/m2 (range 0-994 mg/m2) and 10.330 mg/m2 (range
0-14.460 mg/m2), respectively. Patients treated at the two highest dose levels
experienced NCl grade 0 or 1 toxicities in 73% to 92% of the courses. Three
patients have developed acute myeloid leukaemia, and two of them have
demonstrated abnormalities compatible with topoisomerase II-poison-related
karyotypic changes. CONCLUSIONS: Tailored adjuvant G-CSF-supported FEC
polychemotherapy will make it possible for all patients to be treated at
equivalent levels of haematological toxicity with significantly higher doses
without a marked increase in other organ toxicities.
PMID- 9636832
TI - Clinical course of breast cancer patients with metastases confined to the lungs
treated with chemotherapy. The University of Texas M.D. Anderson Cancer Center
experience and review of the literature.
AB - PURPOSE: To evaluate the clinical course of patients with a metastatic breast
cancer (MBC) confined to the lungs and treated with doxorubicin/cyclophosphamide
containing chemotherapy (DC-CT). PATIENTS AND METHODS: Between 1973 and 1985,
1581 patients with MBC were treated with DC-CT at M.D. Anderson Cancer Center.
Data for 88 patients (5.6%) with metastases confined to the lungs were reviewed
to correlate various clinical characteristics with response to treatment and
survival. RESULTS: The overall response rate was 76% with 33% achieving complete
response (CR). The median overall survival time was 22 months (range 1-210). The
10-year survival rate was 9%. The overall response and CR rates were higher for
the patients with metastases confined to the lungs (76% and 33%. respectively)
than for the remainder of MBC patients (64% and 14%; P < 0.01). The 10-year
survival rate was also higher (9% versus 3%, P < 0.01), but there were no
differences in median overall survival rate. CONCLUSIONS: This retrospective
analysis demonstrated that patients with metastases confined to the lungs treated
with DC-CT had a high objective response rate, especially high CR rates, and a
median survival comparable to that of our entire population of MBC patients. A
small but clinically significant percentage of patients had prolonged survival.
Therefore, not all visceral sites are indicators of poor prognosis.
PMID- 9636833
TI - Survival of patients with visceral metastatic melanoma from an occult primary
lesion: a retrospective matched cohort study.
AB - BACKGROUND: Malignant melanoma presents as metastatic disease without an apparent
primary in about 4% of cases. These are referred to as occult primary melanoma
(OPM). It is not known whether these represent de novo malignant transformation
in non-cutaneous sites or the disappearance of an unrecognised primary, perhaps
on an immunological basis. We hypothesised that OPM might have a superior
prognosis compared to patients with similar disease extent from a known primary
lesion (KPM). PATIENTS AND METHODS: We performed a retrospective cohort survival
study of 146 patients with OPM and visceral metastases treated at the Sydney
Melanoma Unit between 1983 and 1996. A control group of patients with KPM was
matched for age, sex and site of visceral metastases. Survival was measured from
the date of diagnosis of visceral metastases. RESULTS: Patients with OPM had a
median survival of 233 days, significantly longer than the 176 days for those
with KPM (P = 0.024; logrank test). Multivariate analysis allowing for
simultaneous or prior involvement of lymph nodes, subcutaneous tissues or bone,
and site of visceral involvement showed a significantly superior survival for OPM
(hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.55-0.93). A small part
of the effect was explained by treatment, but models allowing for this still
showed a significantly longer survival. CONCLUSIONS: Survival was longer in OPM
patients. This may reflect an intrinsically superior host-tumour interaction.
PMID- 9636834
TI - Ovarian cancer cisplatin-resistant cell lines: multiple changes including
collateral sensitivity to Taxol.
AB - BACKGROUND: Alteration in apoptosis pathways (in particular mutations of p53
gene) may result in resistance of ovarian carcinoma to cisplatin. However,
cisplatin resistance is likely to be multifactorial. An understanding of the
molecular alterations associated with the development of resistance may be of
considerable relevance in an attempt to optimize the therapeutic approach. STUDY
DESIGN: Two cisplatin-resistant sublines (IGROV-1/Pt0.5 and IGROV-1/Pt1), both
characterized by mutant p53 (Cancer Res 1996; 56: 556-62), but with different
degree of resistance were studied in terms of pattern of cross-resistance,
susceptibility to drug-induced apoptosis, expression of gluthathione-dependent
system, cellular pharmacokinetics, drug-induced DNA damage. The resistance index
(ratio between the IC50 of resistant and sensitive cells) after a 96-hour drug
exposure was 10 for IGROV-1/Pt0.5 and 14 for IGROV-1/Pt1 cells. RESULTS:
Resistant cells were cross-resistant to DNA-damaging agents and, interestingly,
they had a collateral sensitivity to Taxol. The cellular response to Taxol
paralleled the drug ability to induce apoptosis. The intracellular glutathione
level was significantly increased in IGROV-1/Pt cells compared to the sensitive
counterpart. In contrast, glutathione S-transferase level was consistently
reduced in both sublines. gamma-Glutamyl transpeptidase activity, which was lower
in resistant than in sensitive cells, was not directly correlated with
glutathione level, thus suggesting a complex regulation of cellular glutathione
content. In the resistant cells with the highest glutathione content, a reduced
level of cisplatin-induced cross-link was found. Analysis of DNA platination
revealed a slight decrease of DNA-bound platinum only in IGROV-1/Pt1 cells.
Again, this reduction is consistent with a protective role for glutathione. The
expression of metallothionein IIa was increased in both resistant variants.
CONCLUSIONS: Multiple changes are involved in acquired resistance of ovarian
carcinoma cells including reduced susceptibility to apoptosis as consequence of
inactivation of p53 and expression of defence mechanisms. The relative
contribution is related to the degree of drug resistance. In particular, the
glutathione-dependent system could have a role only in the development of a high
degree of resistance. Finally, the finding that Taxol was very effective in
inducing apoptosis in resistant sublines with p53 mutation supports the
expression of an intact p53-independent pathway of apoptosis and suggests the
pharmacological interest of Taxol in the treatment of p53-mutated tumors.
PMID- 9636835
TI - A novel cancer vaccine composed of human-recombinant epidermal growth factor
linked to a carrier protein: report of a pilot clinical trial.
AB - BACKGROUND: There is evidence of a relationship between epidermal growth factor
(EGF) and tumor cell proliferation, such as the overexpression of EGF receptor
(EGF-R) in different human tumors, which makes this system an interesting target
for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies
against the EGF-R has been assayed in clinics. Our approach consists of active
immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to
define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled
to a carrier protein. PATIENTS AND METHODS: Ten patients with histologically
proven malignant carcinomas (colon, lung, stomach and prostate) in advanced
clinical stages were enrolled. Patients were immunized twice (on days 0 and 15)
with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64K Neisseria
Meningitidis recombinant protein (P64k, five patients), intradermically, using
aluminium hydroxyde as adjuvant. RESULTS: In both groups 60% of patients
developed anti-EGF antibody titers without evidence of toxicity. Secondary
reactions were very mild, limited to erythema and itching at the site of
injection, which disappeared without medication. CONCLUSIONS: We conclude that
the proposed vaccination with hu-EGF was well tolerated and that antibody titers
against self EGF were developed. The results of this trial may be useful in the
design of new clinical trials with higher dose immunization protocols and using
more effective adjuvants.
PMID- 9636836
TI - Malignant effusions contain lysophosphatidic acid (LPA)-like activity.
AB - BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are
bioactive phospholipids with mitogenic and growth factor-like activities that act
via specific cell-surface receptors present in many normal and transformed cell
types. LPA has recently been implicated as a growth factor present in ascites of
ovarian cancer patients. The presence of LPA-like activity and the hypothesis
that levels of this bioactivity in effusions of ovarian cancer patients are
higher than those in effusions of other cancer patients was studied. MATERIALS
AND METHODS: A neurite retraction bioassay in a neuroblastoma cell line
previously developed for in vitro detection of LPA activity on cell lines was
employed and bioactivity was expressed in virtual LPA-equivalent levels. LPA
equivalent levels were tested in effusions of 62 patients with a range of
malignancies, including 13 ovarian cancer patients. Biochemical and clinical
parameters were evaluated for correlations with LPA-equivalent levels. RESULTS:
Average LPA-equivalent levels were 50.2 microns (range 5.4-200) for all patients,
and 94.5 microns (range 15-200) for ovarian cancer patients (P = 0.004). There
were no additional independent significant correlations between LPA-equivalent
levels in effusions and a range of other biochemical and clinical
characteristics. CONCLUSION: These data suggest a role for LPA-like lipids in the
peritoneal spread of ovarian cancer and possibly that of other predominantly
intraperitoneal malignancies.
PMID- 9636837
TI - Carboplatin toxic effects on the peripheral nervous system of the rat.
AB - BACKGROUND: The most striking of carboplatin's advantages (CBDCA) over cisplatin
(CDDP) is its markedly reduced rate of neurotoxic effects. However, the use of
CBDCA higher-intensity schedules and the association with other neurotoxic drugs
in polychemotherapy may cause some concern about its safety with respect to
peripheral nervous system damage. MATERIALS AND METHODS: Two different schedules
of CBDCA administration (10 mg/kg and 15 mg/kg i.p. twice a week for nine times)
were evaluated in Wistar rats. Neurotoxicity was assessed for behavioral (tail
flick test), neurophysiological (nerve conduction velocity in the tail nerve),
morphological, morphometrical and analytical effects. RESULTS: CBDCA
administration induced dose-dependent peripheral neurotoxicity. Pain perception
and nerve conduction velocity in the tail were significantly impaired,
particularly after the high-dose treatment. The dorsal root ganglia sensory
neurons and, to a lesser extent, satellite cells showed the same changes as those
induced by CDDP, mainly affecting the nucleus and nucleolus of ganglionic sensory
neurons. Moreover, significant amounts of platinum were detected in the dorsal
root ganglia and kidney after CBDCA treatment. CONCLUSIONS: CBDCA is neurotoxic
in our model, and the type of pathological changes it induces are so closely
similar to those caused by CDDP that it is probable that neurotoxicity is induced
in the two drugs by the same mechanism. This model can be used alone or in
combination with other drugs to explore the effect of CBDCA on the peripheral
nervous system.
PMID- 9636838
TI - Psoriasiform lesions as paraneoplastic manifestation in Hodgkin's disease.
PMID- 9636839
TI - Irinotecan-induced immune thrombocytopenia.
AB - BACKGROUND: Irinotecan is currently used as second-line chemotherapy for advanced
colorectal cancer. We report a case of severe thrombocytopenia after Irinotecan,
suggesting an immune mechanism, in a 53-year-old patient. PATIENTS AND METHODS:
The patient's sera were screened for platelet antibodies with an indirect
platelet immunofluorescence test (PIIFT). The monoclonal antibody immobilization
of platelet antigen assay (MAIPA) was used to characterize the antibody target.
RESULTS: We detected an IgG platelet antibody in the patient's serum in the
presence of Irinotecan by means of PIIFT, and not in the presence of SN-38, its
active metabolite. The specificity of the binding was asserted after CD32 MoAb
blockade. The platelet binding site could not be strictly identified with MAIPA
and immunoblotting but GpIIb/IIIa can be excluded after experiments with
Glanzmann platelets. CONCLUSION: This case can be considered the first documented
Irinotecan-induced immune thrombocytopenia.
PMID- 9636840
TI - A phase II study of a novel gemcitabine plus cisplatin regimen administered every
three weeks for advanced non-small-cell lung cancer.
AB - BACKGROUND: The aim of this study was to determine the clinical activity and
toxicity of a novel chemotherapy combination regimen of gemcitabine plus
cisplatin, administered every three weeks, in patients with advanced non-small
cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six previously untreated
stages III (14) and IV (12) patients were included. Gemcitabine was administered
on days 1 and 8 at a dose of 1250 mg/m2 and cisplatin was administered at a dose
of 100 mg/m2 on day 1, every 21 days. RESULTS: Twenty-five patients were
evaluable for response. One patient achieved a complete response, and 16 patients
partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The
main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the
patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity
was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or
omitted due to toxicity. The actual dose-intensity of gemcitabine was 715
mg/m2/week, and 31 mg/m2/week for cisplatin. These figures represent the 86% and
93% of the theoretical dose intensity of both drugs, respectively. With a median
follow-up of 10 months (range 7-13), 17 patients are still alive and nine have
died. The median overall survival is 12 months. CONCLUSION: This novel
combination of gemcitabine and cisplatin administered every three weeks is well
tolerated and induces a remarkably high response rate. The regimen proves more
interesting than the four-week schedules, particularly regarding patients who are
candidates for local therapy.
PMID- 9636841
TI - More on dose-intensity of anthracyclines in breast cancer.
PMID- 9636842
TI - Actinomycosis.
PMID- 9636843
TI - Immunomodulation for the treatment of invasive fungal infections.
PMID- 9636844
TI - Combination immunotherapy and antifungal chemotherapy.
AB - Historical clinical observations suggested that cellular immunity is central in
the outcome of deep fungal infections, and experimental observations later proved
this. Unstimulated effector cells interact synergistically with antifungal drugs.
Recombinant cytokines, of which interferon gamma (IFN-gamma) is the most
prominent, stimulate several host-effector cells (macrophages, monocytes,
neutrophils) for antifungal activity. Effector cells stimulated by such molecules
(data with macrophage colony-stimulating factor, granulocyte colony-stimulating
factor, and granulocyte-macrophage colony-stimulating factor with azoles are
presented as examples) also have enhanced synergistic activity with antifungals.
A tilt toward a type 1 T-helper (Th1) cell pathway seems essential in antifungal
host defenses. Cytokines (and anticytokines) that promote this pathway can be
protective in vivo and act cooperatively with antifungal drugs. Observations with
interleukin (IL)-12, IFN-gamma, and anti-IL4 illustrate this. The clinical
applications of these strategies are just beginning.
PMID- 9636845
TI - The potential role of cytokine therapy for fungal infections in patients with
cancer: is recovery from neutropenia all that is needed?
AB - Optimal regimens for the treatment of invasive fungal infections have yet to be
defined, and these life-threatening conditions are one of the leading causes of
treatment failure in patients with cancer. A substantial body of preclinical work
points in the direction of using cytokines as immunomodulators of the multiple
deficiencies involved in the progression of fungal infections in neutropenic and
nonneutropenic cancer patients. These deficiencies include not only the easily
recognized deficiencies in cell quantity but also subtle deficiencies of cell
function. Four cytokines (granulocyte colony-stimulating factor, granulocyte
macrophage colony-stimulating factor, macrophage colony-stimulating factor, and
interferon gamma) show promise as adjuvant therapy for proven fungal infections
in this setting, although clinical experience is still limited. As an additional
approach, the concept of white blood cell transfusions has been revived by the
use of granulocyte colony-stimulating factor and promises to be helpful in the
setting of neutropenia.
PMID- 9636846
TI - Use of macrophage colony-stimulating factor in the treatment of fungal
infections.
AB - Management of fungal infections is a major medical problem. The risk of
developing a fungal infection is higher for patients who are undergoing dose
intensive therapy, are immunocompromised, have neutropenia, are receiving
prophylactic antibiotics, have other infections, have invasive catheters, or have
a history of severe trauma or burns. Survival is decreased among patients who
develop fungal infection in these situations. In view of the high morbidity and
mortality associated with fungal infections in transplant recipients, cytokines
that enhance cell function, such as macrophage colony-stimulating factor (M-CSF),
have been investigated. M-CSF enhances cytotoxicity, superoxide production,
phagocytosis, chemotaxis, and secondary cytokine production in monocytes and
macrophages. Animal models and clinical data suggest efficacy of M-CSF in
controlling fungal infection.
PMID- 9636847
TI - Monocyte-macrophages, granulocyte-macrophage colony-stimulating factor, and
prolonged survival among patients with acute myeloid leukemia and stem cell
transplants.
AB - Recombinant GM-CSF has been recently shown to prolong survival of elderly
patients with acute myeloid leukemia (AML) by reducing the rate of induction
therapy-related mortality. In a prospective, randomized, placebo-controlled,
double-blind, multicenter study conducted by the Eastern Cooperative Oncology
Group in the United States, granulocyte-macrophage colony-stimulating factor (GM
CSF) was given only to those patients who had hypocellular or remission marrow on
day 10 of one or two cycles of standard induction therapy. Although the
administration of GM-CSF significantly reduced a wide range of adverse events,
the main benefit of this cytokine seems to be mediated by a reduction in sepsis.
A similarly designed study, conducted by the Southwest Oncology Group in a
directly comparable AML patient population with use of granulocyte colony
stimulating factor (G-CSF) as the supportive cytokine, showed no survival benefit
and no reduction in the rates of serious or lethal sepsis. In most current
clinical situations, GM-CSF and G-CSF are indistinguishable both in terms of
efficacy and toxicity. GM-CSF and G-CSF have very different impacts on the
survival of patients with AML. The stimulation of monocyte-macrophage function
and proliferation by GM-CSF may mediate the selective benefit of GM-CSF in
patients with AML and stem cell transplants. GM-CSF merits further study as
therapy for and/or protection against opportunistic sepsis in patients with
cancer and will be included in a number of International Oncology Study Group
protocols.
PMID- 9636848
TI - Treatment of acute myeloid leukemia with cytokines: effect on duration of
neutropenia and response to infections.
AB - Clinical data regarding the use of colony-stimulating factors for the treatment
of acute myeloid leukemia (AML) are conflicting because of varying study
conditions. Interpretation of data is affected by differences in patients' ages,
induction regimens, the timing of growth factor administration, the presence of
marrow hypoplasia, disease states, differences in the products used, and
statistical endpoints. Most trials of granulocyte colony-stimulating factor (GM
CSF) have demonstrated a significant shortening of neutrophil recovery time and a
trend toward higher rates of complete remission. Several studies have
demonstrated a significant reduction in the rates of morbidity or early mortality
with G-CSF or GM-CSF. In vitro data support the concept of enhancing
antimicrobial activity with macrophage colony-stimulating factor or GM-CSF. The
safety and potential benefit of these cytokines suggest that cytokines should be
administered to patients receiving induction therapy for AML who are at high risk
for therapy-related morbidity and mortality.
PMID- 9636849
TI - Photo quiz. I. Reactive hemophagocytic syndrome caused by CMV infection.
PMID- 9636850
TI - Characterization of Bartonella henselae isolated from bacillary angiomatosis
lesions in a human immunodeficiency virus-infected patient in Germany.
AB - Infections with Bartonella (Rochalimaea) henselae can result in a variety of
clinical entities, including bacillary angiomatosis in immunocompromised hosts.
The fastidious nature of this bacterium has so far prevented the culture of many
clinical isolates. We report the recovery of the first European B. henselae
isolate associated with bacillary angiomatosis. The isolate was cultured in a
frozen skin biopsy specimen from a human immunodeficiency virus (HIV)-infected
patient and was characterized by means of biochemical, bacteriologic,
immunologic, and molecular biological methods including pulsed-field gel
electrophoresis. This strain was compared with two B. henselae strains isolated
in the United States to determine the relationship between the isolates. We found
that it was phenotypically and genotypically indiscernible from B. henselae
Houston-1, a blood culture isolate from an HIV-infected patient in Houston. These
data suggest that one B. henselae clone is associated with human infections in
Europe and the United States.
PMID- 9636851
TI - Are all Bartonella henselae strains created equal?
PMID- 9636852
TI - Staphylococcus aureus prosthetic valve endocarditis: optimal management and risk
factors for death.
AB - The mortality rate associated with Staphylococcus aureus prosthetic valve
endocarditis (PVE) remains high. To identify clinical events associated with an
increased risk of death among patients with S. aureus PVE and to evaluate the
role of valve replacement surgery in reducing mortality, we conducted a
retrospective cohort study of patients who met strict criteria for definite S.
aureus PVE. The primary endpoint for the study was survival at 3 months from the
date of diagnosis. S. aureus PVE was diagnosed in 33 patients. Of these, 14 (42%)
died within 90 days of the diagnosis. Cardiac complications were detected in 22
(67%), and central nervous system (CNS) complications were detected in 11 (33%).
A stepwise logistic regression multivariate model demonstrated that cardiac
complications, but not CNS complications, were associated with increased
mortality and that performing valve replacement surgery during antibiotic therapy
was associated with decreased mortality. These associations were confirmed by
using a Cox proportional hazards model with time-dependent covariates to control
for survival bias. Performing valve replacement surgery during antimicrobial
therapy will reduce the mortality among patients with S. aureus PVE, even those
without evidence of cardiac complications.
PMID- 9636853
TI - The role of valve replacement in the treatment of prosthetic valve endocarditis.
PMID- 9636854
TI - Once-daily sparfloxacin versus high-dosage amoxicillin in the treatment of
community-acquired, suspected pneumococcal pneumonia in adults. Sparfloxacin
European Study Group.
AB - The objective of this randomized, double-blind, multicenter study of 329 adult
patients requiring hospitalization was to compare the safety and efficacy of
sparfloxacin at a dosage of 200 mg once daily (following a 400-mg loading dose on
day 1) with those of amoxicillin given as a 1-g oral dose three times daily for
treatment of community-acquired pneumonia suspected to be due to Streptococcus
pneumoniae. Success of treatment was determined by a combination of clinical
assessment and chest radiography. Pneumococcal pneumonia was the confirmed
diagnosis for 177 patients (54%). Overall rates of success among evaluable
patients were equivalent between drugs, both at the end of treatment
(sparfloxacin, 92%; amoxicillin, 87%) and at follow-up (sparfloxacin, 89%;
amoxicillin, 84%). Sparfloxacin was well-tolerated and produced fewer
gastrointestinal effects than amoxicillin. In conclusion, sparfloxacin is a safe
and effective alternative to high-dose amoxicillin for the treatment of suspected
pneumococcal community-acquired pneumonia.
PMID- 9636855
TI - Photo quiz. II. Disseminated histoplasmosis.
PMID- 9636856
TI - A new fluoroquinolone for community-acquired pneumonia.
PMID- 9636858
TI - Comparison of two methods for the assessment of delayed-type hypersensitivity
skin responses in patients with human immunodeficiency virus infection.
AB - We compared two techniques for detecting delayed-type hypersensitivity (DTH) skin
responses in 359 patients infected with human immunodeficiency virus (HIV) (mean
CD4+ lymphocyte count, 387/microL). DTH responses were assessed with use of two
antigenic panels administered simultaneously: tuberculin purified protein
derivative (PPD) plus three control antigens (Candida albicans, mumps antigen,
and tetanus toxoid) administered by the Mantoux method and by a multiple-puncture
device delivering seven antigens percutaneously (MULTITEST CMI; Institut Merieux,
Lyon, France). Eighty-three patients (23%) were anergic, 216 (60%) reacted to
both panels, 55 (15%) did not react to MULTITEST CMI but did react to the
antigens administered by Mantoux method, and only five (1%) reacted to MULTITEST
CMI without reacting to antigens administered by the Mantoux method (P < .001,
McNemar's test). Each of the three possible combinations of PPD plus two control
antigens administered by the Mantoux method were also superior to MULTITEST CMI
for classifying patients as nonanergic (P < .001, McNemar's test). We conclude
that the application of antigens by the Mantoux method is more efficient than
MULTITEST CMI for detecting DTH skin responses in HIV-infected patients.
PMID- 9636857
TI - Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum
immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum.
AB - Bovine hyperimmune anti-Cryptosporidium colostrum immunoglobulin (BACI) decreases
the intensity of Cryptosporidium parvum infection in vitro. We investigated the
prophylactic effect of BACI in healthy adults challenged with C. parvum. After we
established an oocyst dose that resulted in 100% infection in four volunteers
(baseline group), 16 volunteers were randomized to receive (1) BACI prior to C.
parvum challenge (BACI group) and a nonfat milk placebo 30 minutes later, (2)
BACI prior to and 30 minutes after challenge (reinforced BACI group), or (3)
nonfat milk placebo prior to and 30 minutes after challenge. Subjects received
BACI (10 g) or nonfat milk placebo three times a day for a total of 5 days and
were followed for clinical symptoms and oocyst excretion for 30 days. A trend
toward less diarrhea (P = .08) was observed for subjects receiving BACI in
comparison with occurrences in placebo recipients. Subjects receiving BACI or
nonfat milk placebo had a 100-fold reduction in oocyst excretion as compared with
excretion in the baseline group.
PMID- 9636859
TI - Chronic follicular conjunctivitis associated with Chlamydia psittaci or Chlamydia
pneumoniae.
AB - We determined whether patients with chronic conjunctivitis in whom direct
fluorescent antibody (DFA) tests revealed genus-specific chlamydial antigens (but
not species-specific Chlamydia trachomatis antigens) were infected with Chlamydia
psittaci or Chlamydia pneumoniae. Patients were divided into a case group of
possible non-trachomatis chlamydial conjunctivitis and a control group of
nonchlamydial conjunctivitis on the basis of examination and DFA testing. Species
specific primers were used to amplify C. trachomatis, C. psittaci, and C.
pneumoniae DNA with polymerase chain reaction (PCR). Four (27%) of 15 samples
from the case group were positive for C. psittaci or C. pneumoniae DNA, whereas
none of 24 control samples were positive. Sequencing revealed a C. pneumoniae, an
avian C. psittaci, and two mammalian C. psittaci strains. A short course of oral
antibiotic treatment appears to be inadequate for patients with non-trachomatis
chlamydial conjunctivitis. Ocular infections due to C. pneumoniae and C. psittaci
may be more common than previously recognized and can be identified by DFA and
PCR.
PMID- 9636860
TI - Why have group A streptococci remained susceptible to penicillin? Report on a
symposium.
AB - In spite of 50 years of extensive use of penicillin, group A streptococci remain
exquisitely susceptible to this antibiotic. This observation that continuing
susceptibility has occurred despite the development of resistance to other
antimicrobial agents prompted a day-long meeting at Rockefeller University (New
York) in October 1996. Among the most likely explanations for this remarkable
state of continued susceptibility to penicillin are that beta-lactamase may not
be expressed or may be toxic to the organism and/or that low-affinity penicillin
binding proteins either are not expressed or render organisms nonviable. Other
potential explanations are that circumstances favorable for the development of
resistance have not yet occurred and/or that there are inefficient mechanisms for
or barriers to genetic transfer. Recommended future actions include (1)
additional laboratory investigations of gene transfer, penicillin-binding
proteins, virulence factors, and homeologous recombination and mismatch repair;
(2) increased surveillance for the development of penicillin resistance; (3)
application of bioinformatics to analyze streptococcal genome sequences; and (4)
development of vaccines and novel antimicrobial agents. Thus far the
susceptibility of group A streptococci to penicillin has not been a major
clinical or epidemiological problem. A similar observation, however, could have
been made decades ago about Streptococcus pneumoniae. It is therefore vital for
the scientific community to closely examine why penicillin has remained uniformly
highly active against group A streptococci in order to maintain this desirable
state.
PMID- 9636861
TI - Clinical outcome of invasive infections by penicillin-resistant Streptococcus
pneumoniae in Korean children.
AB - One hundred six cases of invasive pneumococcal infections diagnosed from 1985 to
1996 were analyzed retrospectively. The types of infection were bacteremia
without focus (45%), meningitis (19%), peritonitis (17%), pneumonia (bacteremic)
(16%), and others (3%). Penicillin-nonsusceptible Streptococcus pneumoniae was
first detected in 1989, and its incidence increased rapidly thereafter, reaching
89% in 1995. Initial empirical regimens were of parenteral beta-lactam
antimicrobials with or without an aminoglycoside, but these were modified
subsequently. Among the 72 nonmeningeal infections analyzed, a favorable response
at 72 hours and death were observed in 83% and 2.5%, respectively, of 40
penicillin-susceptible infections, as compared with 86% (P = 1.0) and 7.1% (P =
.45) of 14 infections due to intermediate strains and 61% (P = .07) and 11% (P =
.22) of 18 due to resistant strains. The favorable-response rate and mortality
among 49 patients not in initially critical condition were 92% and zero,
respectively, as compared with 52% (P = .00027) and 17% (P = .008) of 23 in
critical condition. The data suggest that clinical outcome of penicillin
nonsusceptible pneumococcal infection outside the CNS may be more closely related
to clinical condition at presentation than to the level of resistance of the
causative strain when such infection is treated with parenteral beta-lactams.
PMID- 9636862
TI - Invasive Streptococcus pneumoniae infection in Latin American children: results
of the Pan American Health Organization Surveillance Study.
AB - Protein-polysaccharide conjugate vaccines against Streptococcus pneumoniae
promise to be an effective public health intervention for children, especially in
an era of increasing antimicrobial resistance. To characterize the distribution
of capsular types in Latin America, surveillance for invasive pneumococcal
infection in children < or = 5 years of age was done in six countries between
February 1993 and April 1996. Fifty percent of 1,649 sterile-site isolates were
from children with pneumonia, and 52% were isolated from blood. The 15 most
common of the capsular types prevalent throughout the region accounted for 87.7%
of all isolates. Overall, 24.9% of isolates had diminished susceptibility to
penicillin: 16.7% had intermediate resistance and 8.3% had high-level resistance.
Three customized vaccine formulas containing 7, 12, and 15 capsular types were
found to have regional coverages of 72%, 85%, and 88%, respectively. This study
emphasizes the need for local surveillance for invasive pneumococcal disease
prior to the development and evaluation of protein-polysaccharide conjugate
vaccines for children.
PMID- 9636863
TI - Combination therapy with fluconazole and flucytosine for cryptococcal meningitis
in Ugandan patients with AIDS.
AB - We performed a randomized trial in which combination therapy with fluconazole and
short-term flucytosine was compared with fluconazole monotherapy in 58 patients
with AIDS-associated cryptococcal meningitis (CM). Thirty of these patients were
randomized to receive combination therapy with fluconazole, 200 mg once a day for
2 months, and flucytosine, 150 mg/(kg.d) for the first 2 weeks, and 28 were
randomized to receive monotherapy with fluconazole at the same dose for 2 months.
Patients in both groups who survived for 2 months received fluconazole as
maintenance therapy at a dose of 200 mg three times per week for 4 months. The
combination therapy prevented death within 2 weeks and significantly increased
the survival rate among these patients (32%) at 6 months over that among patients
receiving monotherapy (12%) (P = .022). The combination therapy also resulted in
a significant decrease in the severity of headache after 1 month of treatment,
compared with monotherapy (P = .005). No serious adverse reactions were observed
in patients receiving either regimen. These data indicate that treatment with
fluconazole and short-term flucytosine is a cost-effective and safe regimen that
improves the quality of life for patients with AIDS-associated CM in developing
countries where human immunodeficiency virus is endemic.
PMID- 9636864
TI - Reflections on studies in developing countries.
PMID- 9636865
TI - A double-blind comparison of itraconazole oral solution and fluconazole capsules
for the treatment of oropharyngeal candidiasis in patients with AIDS.
AB - This double-blind trial compared the clinical and mycological efficacy and safety
of itraconazole oral solution with those of fluconazole capsules in the treatment
of oropharyngeal candidiasis in patients with AIDS. A total of 244 patients were
enrolled and randomized to one of three groups for treatment with itraconazole
oral solution (100 mg twice daily for 7 days or 100 mg once daily for 14 days) or
fluconazole capsules (100 mg once daily for 14 days). Among 194 evaluable cases,
complete response (clearance of all symptoms and signs) or marked improvement was
noted in 54 of 60 patients (90%) receiving once-daily itraconazole and in 65 of
72 fluconazole-treated patients (90%) at the end of treatment; these results were
statistically equivalent (P = .0024). Twice-daily itraconazole produced a
clinical response in 51 of 62 patients (82%). The groups were equivalent in terms
of early relapse (within the 18-day period studied); 37% of patients in the twice
daily itraconazole group, 35% in the once-daily itraconazole group, and 34% in
the fluconazole group relapsed. Drug tolerability was comparable between the
three groups. These results show that, in the treatment of oropharyngeal
candidiasis, itraconazole oral solution and fluconazole capsules at a 100-mg
single daily dose for 14 days are equally effective.
PMID- 9636866
TI - An outbreak of Pontiac fever among children following use of a whirlpool.
AB - We investigated an outbreak of fever, most likely due to a contaminated
whirlpool, among nine adults and six children residing in a summerhouse. The
outbreak was characterized by a high attack rate, short incubation periods,
influenza-like symptoms, and rapid recoveries, all features typical of Pontiac
fever. However, the children had less-characteristic symptoms than the adults,
and they did not have any sequelae. Findings on the children's chest radiographs
were unremarkable, and none of the children had leukocytosis. Evidence of
Legionella pneumophila infection was found in six cases: in one case by isolation
of L. pneumophila serogroup 1 and detection of legionellae by PCR, and in five
cases by seroconversion to the clinical isolate. Six additional cases had
presumptive evidence of legionella infection, with seroconversion to Legionella
micdadei antigen; a PCR assay was also positive for legionellae for one of these
cases. In contrast, two adult nonusers of the whirlpool had no symptoms and no
serological evidence of infection. Serological testing and cultures for other
pathogens, as well as cultures of all environmental samples, were negative. This
investigation demonstrates the differences between adults and children with
respect to the clinical picture of Pontiac fever; furthermore, it shows that
culture and PCR assay of tracheal aspirates for legionellae can be performed in a
hospital setting for rapid diagnosis, although the sensitivities of these methods
are low.
PMID- 9636867
TI - Gamma knife radiosurgery and albendazole for cerebral alveolar hydatid disease.
AB - Standard treatment of cerebral alveolar hydatid disease consists of open brain
surgery and systemic albendazole. We describe a patient with inoperable cerebral
alveolar hydatid cysts on whom gamma knife radiosurgery was used instead of open
brain surgery. Because of the size of the multicystic lesion, the gamma knife
procedure was done in two sessions. Repeated courses of albendazole were given
concurrently. Magnetic resonance imaging follow-up studies showed marked
shrinkage of the irradiated cystic structures and initially increased perifocal
edema. At a follow-up visit 3 years after gamma knife radiosurgery, the
polycystic lesion, the perifocal edema, and the neurological symptoms had all
markedly decreased. The patient is now stable and has minimal neurological
symptoms, and the quality of her life has improved. Gamma knife radiosurgery may
be an alternative for patients with cerebral alveolar hydatid disease for whom
surgery is not possible.
PMID- 9636868
TI - Amphotericin B lipid complex for invasive fungal infections: analysis of safety
and efficacy in 556 cases.
AB - The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were
evaluated in 556 cases of invasive fungal infection treated through an open
label, single-patient, emergency-use study of patients who were refractory to or
intolerant of conventional antifungal therapy. All 556 treatment episodes were
evaluable for safety. During the course of ABLC therapy, serum creatinine levels
significantly decreased from baseline (P < .02). Among 162 patients with serum
creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the
mean serum creatinine value decreased significantly from the first week through
the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases
evaluable for therapeutic response, there was a complete or partial response to
ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of
42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and
82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern
of invasive fungal infection, underlying condition, and reason for enrollment
(intolerance versus progressive infection). These findings support the use of
ABLC in the treatment of invasive fungal infections in patients who are
intolerant of or refractory to conventional antifungal therapy.
PMID- 9636869
TI - Rapid simultaneous diagnosis of infections with respiratory syncytial viruses A
and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3
by multiplex quantitative reverse transcription-polymerase chain reaction-enzyme
hybridization assay (Hexaplex).
AB - A multiplex quantitative reverse transcription-polymerase chain reaction-enzyme
hybridization assay (Hexaplex; Prodesse, Milwaukee) was developed and used to
rapidly detect and quantitate RNA of respiratory syncytial viruses A and B,
influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 in
nasal wash specimens in a single test. Primers and probes originated from highly
conserved regions of each viral genome. Six and a half primer pairs were mixed
for the simultaneous detection and quantitation of RNA from seven different
respiratory viruses. We tested 109 clinical samples with this assay. Twenty-nine
virus culture-positive samples were all positive by Hexaplex. Samples from 40
symptomatic patients were negative by virus culture, but eight of these were
positive by Hexaplex. Forty samples from asymptomatic children were negative by
both virus culture and Hexaplex. No cross-reactions were noted among 17 different
respiratory viruses with use of this assay. Hexaplex was 100% sensitive (95%
confidence interval [CI], 0.88-1.0) and 98% specific (95% CI, 0.97-0.99). All
eight "false-positive" Hexaplex results (in comparison with negative viral
culture results) were for symptomatic patients with low numbers of virus RNA
copies. This finding suggests that Hexaplex may be more sensitive than virus
culture. Our data demonstrate that Hexaplex is a rapid, sensitive, and specific
quantitative test for the diagnosis of infections with these seven common
respiratory viruses.
PMID- 9636870
TI - Disseminated sporotrichosis and Sporothrix schenckii fungemia as the initial
presentation of human immunodeficiency virus infection.
AB - Infection with Sporothrix schenckii causes a localized lymphocutaneous disease in
the immunocompetent host, while it frequently results in disseminated disease in
the immunocompromised patient. There are a growing number of reports of S.
schenckii infection in the human immunodeficiency virus (HIV)-infected
population, where the disease usually starts as a localized cutaneous lesion and
subsequently disseminates. The optimal treatment of systemic sporotrichosis in
HIV-positive patients is as yet unknown. This article presents a case report of
disseminated sporotrichosis in an HIV-infected patient, a review of the
literature, and discussion of treatment options for HIV-infected patients.
PMID- 9636871
TI - Comparison of serum galactomannan antigen detection and competitive polymerase
chain reaction for diagnosing invasive aspergillosis.
AB - To improve the diagnosis of invasive aspergillosis (IA), we retrospectively
compared competitive polymerase chain reaction (PCR) and sandwich ELISA for
detection of serum galactomannan (GM) antigen. We studied 281 serum samples
collected weekly during the period at risk for IA from 41 selected hematology
patients. Twenty-two patients had confirmed, probable, or suspected IA, according
to clinical and mycologic data. Fifteen of them had positive GM titers (87
samples) and 12 had positive PCRs (20 samples). Nineteen of the 20 PCR-positive
samples were also GM-positive. Of the 19 patients without IA (83 samples), one
had 3 GM-false-positive samples. Neither test anticipated the initiation of
antifungal therapy on the basis of clinical suspicion. Both tests were more
likely to be positive before death. This study suggests that PCR on serum samples
is not more sensitive than GM detection. However, PCR can improve the specificity
of the GM test. Together, these noninvasive tests should improve the diagnosis of
IA.
PMID- 9636872
TI - Clinical significance and outcome of anaerobic bacteremia.
AB - We retrospectively studied the incidence of anaerobic bacteremia during 6 years
(1991-1996) at Turku University Central Hospital (Turku, Finland). The clinical
significance of a positive anaerobic blood culture, the effect of a positive
culture on the choice of antimicrobial therapy, and the outcome for patients were
evaluated. Cultures of blood from 81 patients yielded anaerobic bacteria (4% of
all bacteremias). Anaerobic bacteremia was clinically significant in 57 patients
(0.18 cases per 1,000 admissions). Only half (28) of these patients received
appropriate and effective antimicrobial treatment before the results of blood
cultures were reported; for 18 patients (32%), initially ineffective treatment
was changed on the basis of the bacteriologic results, and for 11 patients (19%),
the treatment was not changed. The mortality in these patient groups was 18%,
17%, and 55%, respectively. Empirical therapy may provide coverage for anaerobes
in only half of the patients with anaerobic bacteremia, and failure to pay
attention to the results of anaerobic blood cultures may have serious
consequences for patients.
PMID- 9636873
TI - Common emergence of amantadine- and rimantadine-resistant influenza A viruses in
symptomatic immunocompromised adults.
AB - The importance and significance of amantadine- or rimantadine-resistant influenza
viruses in immunocompromised patients was studied in a population of adult bone
marrow transplant (BMT) recipients and patients with leukemia prospectively
cultured for respiratory viruses. Influenza A viruses were isolated from 29
patients with acute respiratory illness (14 BMT recipients and 15 patients with
leukemia). Fifteen patients (52%) received amantadine (n = 4) or rimantadine (n =
11) therapy. All influenza isolates recovered from six patients shedding virus
for > or = 3 days were screened for antiviral susceptibility; resistant isolates
were further genetically characterized. Initial influenza isolates were
susceptible to amantadine or rimantadine, but subsequent isolates from five of
six patients were resistant. Influenza-associated mortality was similar among
patients with and without documented antiviral resistance (2 of 5 vs. 5 of 24).
We conclude that development of antiviral resistance in immunocompromised
individuals should be considered when they have been treated with antivirals and
have shed influenza virus for a prolonged period. Isolation procedures should be
instituted for all immunocompromised patients with influenza, both during and
after therapy with amantadine or rimantadine.
PMID- 9636874
TI - Detection of chlamydiosis in a shipment of pet birds, leading to recognition of
an outbreak of clinically mild psittacosis in humans.
AB - Avian chlamydiosis was detected in a shipment of > 700 pet birds from a Florida
bird distributor that were sold to nine Atlanta-area pet stores in August 1995.
Respiratory illness among persons who had recently acquired birds from this
shipment was reported to local public health officials. The attack rate of acute
respiratory illness was 10.7% among persons in households exposed to birds from
the implicated flock vs. 1.8% among control households (odds ratio, 6.60; 95%
confidence interval, 1.39-31.2). Illness and serological evidence of infection in
the absence of symptoms were more common among persons in households with
recently purchased birds that were sick or that had died and among persons who
had had direct contact with the birds. Clinical psittacosis or serological
evidence of Chlamydia psittaci infection was found in 30.7% of households with
birds from the infected flock. Mild illnesses and asymptomatic infections in
exposed persons were unusual features of this outbreak.
PMID- 9636875
TI - Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in
three patients.
AB - Rhinocerebral mucormycosis (zygomycosis) primarily affects diabetic or
immunosuppressed patients and typically progresses rapidly, necessitating
surgical excision and antifungal therapy with amphotericin B. Large doses of
amphotericin B are required for cure, causing significant renal toxicity.
Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals,
Menlo Park, CA) is a 1:1 complex of cholesteryl sulfate and amphotericin B, which
results in significant reduction of toxicity, especially nephrotoxicity. We
describe three patients with life-threatening rhinocerebral mucormycosis treated
with ABCD. All patients had high serum creatinine levels due to prior treatment
with amphotericin B; these levels reverted to normal during treatment with ABCD.
Two patients with diabetes mellitus were cured after receiving a combination of
surgery and ABCD therapy. The third patient, who had myelodysplastic syndrome,
had an initial good response, with cure of the fungal infection; however, he
eventually died of his primary illness. To the best of our knowledge, this is the
first detailed clinical description of the treatment of mucormycosis with ABCD.
PMID- 9636876
TI - Primary liver abscess due to Klebsiella pneumoniae in Taiwan.
AB - Pyogenic liver abscess is an uncommon complication of intra-abdominal or biliary
tract infection and is usually a polymicrobial infection associated with high
mortality and high rates of relapse. However, over the past 15 years, we have
observed a new clinical syndrome in Taiwan: liver abscesses caused by a single
microorganism, Klebsiella pneumoniae. We reviewed 182 cases of pyogenic liver
abscess during the period September 1990 to June 1996; 160 of these cases were
caused by K. pneumoniae alone, and 22 were polymicrobial. When patients with K.
pneumoniae liver abscess were compared with those who had polymicrobial liver
abscess, we found higher incidences of diabetes or glucose intolerance (75% vs.
4.5%) and metastatic infections (11.9% vs. 0) and lower rates of intra-abdominal
abnormalities (0.6% vs. 95.5%), mortality (11.3% vs. 41%), and relapse (4.4% vs.
41%) in the former group. Liver abscess caused by K. pneumoniae is a new clinical
syndrome that has emerged as an important infectious complication in diabetic
patients in Taiwan.
PMID- 9636877
TI - Something's rotten: a nosocomial outbreak of malodorous Pseudomonas aeruginosa.
AB - From July 1994 through November 1996, a phenotypically unique strain of
Pseudomonas aeruginosa producing a pungent, "rotten-potato" odor and a positive
lysine decarboxylase reaction was isolated from 39 patients at UCLA Medical
Center (Los Angeles). Most cases (95%) were in intensive care units and had
clinical infections (72%). Most isolates (74%) were recovered from cultures of
respiratory secretions. To determine risk factors for acquisition of the
organism, 23 cases were compared with 23 randomly selected controls matched by
service and isolate date. Multivariate analysis revealed that isolation of
malodorous P. aeruginosa was associated with mechanical ventilation of > 24
hours' duration (odds ratio [OR] = 9.4; P = .001) and transfer from an outside
hospital (OR = 5.7; P = .04). DNA from outbreak strains hybridized to P.
aeruginosa-specific toxin A and phospholipase C gene probes and all outbreak
isolates tested were found to be identical by use of pulsed-field gel
electrophoresis. An unusual phenotypic characteristic of the strain led to the
recognition of a nosocomial outbreak of P. aeruginosa infection associated with
mechanical ventilation.
PMID- 9636878
TI - Molecular, serological, and clinical features of 16 consecutive cases of invasive
streptococcal disease. Southeastern Minnesota Streptococcal Working Group.
AB - We performed a comprehensive analysis of the molecular, serological, and clinical
features of 16 consecutive cases of invasive streptococcal disease (ISD). The
majority of cases were linked to two group A streptococcus (GAS) clones closely
related by pulsed-field gel electrophoresis (PFGE) and designated as PFGE-1 and
PFGE-1.1. These clones, serotyped as M-3, T-3/B3264, carried an allelic variant
of the gene that encodes pyrogenic exotoxin A (speA3) and the gene that encodes
streptococcal superantigen (SSA) but different emm alleles that encode M-protein.
The characteristics and clinical features of patients were similar to those
described in previous reports, regardless of the responsible GAS clone. However,
worse clinical outcomes (shock and death) were more frequent when patients
infected with PFGE1/1.1 clones were considered as a group and compared with all
other patients as a group. One striking feature in some patients with deep tissue
infection was a lack of inflammatory cells despite the presence of numerous
streptococci. An evaluation of PFGE profiles of GAS isolated elsewhere
demonstrated that the PFGE-1 clone has caused invasive disease in other locations
in the United States and in Japan.
PMID- 9636879
TI - Is prevaccination screening for hepatitis B among sexually active adolescents
cost-effective?
PMID- 9636880
TI - Intraventricular quinupristin/dalfopristin for the treatment of vancomycin
resistant Enterococcus faecium shunt infection.
PMID- 9636881
TI - Epidural abscess due to deep-neck infection.
PMID- 9636882
TI - Retrosternal abscess: a prominent manifestation of infection due to
Staphylococcus aureus.
PMID- 9636883
TI - Simultaneous obstructing and pseudomembranous necrotizing tracheobronchitis due
to Aspergillus flavus.
PMID- 9636884
TI - Intrabiliary rupture of hepatic hydatid cysts: diagnosis by use of magnetic
resonance cholangiography.
PMID- 9636885
TI - Nontuberculous mycobacterial tenosynovitis: report of two cases.
PMID- 9636886
TI - Asymptomatic Mycobacterium avium complex pneumonia complicated by infectious
arthritis/osteomyelitis.
PMID- 9636887
TI - Mycotic aneurysm of the ulnar artery distal to the wrist.
PMID- 9636888
TI - Endocarditis due to Neisseria elongata subspecies nitroreducens: case report and
review.
PMID- 9636889
TI - Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary
disease: report of eight cases and review.
PMID- 9636890
TI - Two-year review of hepatitis A vaccine safety: data from the Vaccine Adverse
Event Reporting System (VAERS).
PMID- 9636891
TI - Cerebral pseudallescheriasis due to Pseudallescheria boydii as the first
manifestation of AIDS.
PMID- 9636892
TI - Isolated pleural effusion with pleural fibrosis in a patient with subacute
progressive disseminated histoplasmosis.
PMID- 9636893
TI - Pathogenesis of fever: are circulating pyrogenic cytokines the only mediators?
PMID- 9636894
TI - Nosocomial infections in patients infected with human immunodeficiency virus.
PMID- 9636895
TI - Utility of the enzyme-linked immunosorbent assay for diagnosing neurobrucellosis.
PMID- 9636896
TI - Another case of breast hypertrophy in a patient treated with indinavir.
PMID- 9636897
TI - Guidelines for the prevention of antimicrobial resistance in hospitals.
PMID- 9636898
TI - Lactobacillus bacteremia and endocarditis.
PMID- 9636899
TI - Rapid emergence of resistance to cefepime during treatment.
PMID- 9636900
TI - Percutaneous inoculation tuberculosis.
PMID- 9636901
TI - Cutaneous infection due to Mycobacterium gordonae in a human immunodeficiency
virus-infected patient.
PMID- 9636902
TI - Retrograde cerebral perfusion: is the brain really being perfused?
PMID- 9636903
TI - Neurophysiologic effects of retrograde cerebral perfusion used for aortic
reconstruction.
AB - OBJECTIVE: The results of neurophysiologic monitoring using somatosensory evoked
potentials (SSEPs) and electroencephalography (EEG) were analyzed to determine if
retrograde cerebral perfusion (RCP) supported central nervous system electrical
function during surgery that required temporary interruption of antegrade
cerebral perfusion (IACP). DESIGN: A prospective, observational study. SETTING: A
university hospital. PARTICIPANTS: Fifteen adult patients who underwent aortic
reconstruction using RCP and three patients who underwent thoracic aortic
operations using hypothermic circulatory arrest without RCP. INTERVENTIONS: SSEPs
and EEG were monitored continuously throughout the operation. Regression analysis
was performed to determine the factors that affected the rate of decrease in SSEP
amplitudes during IACP and the time required for SSEP and EEG activity to recover
after antegrade cerebral perfusion (ACP) was restored. MEASUREMENTS AND MAIN
RESULTS: The amplitude of SSEPs that were elicited decreased over time after
IACP. The mean +/- standard deviation (SD) time required for the brachial plexus
(Erb's point), cervicomedullary junction (N13), and brainstem (N18) SSEPs to
decrease to 0.5 of their original amplitude after IACP were 30 +/- 2, 19 +/- 2,
and 16 +/- 2 minutes, respectively. The rate of decrease in the N18 SSEP
amplitude after IACP correlated positively to the fraction of no-flow time (p =
0.01). CONCLUSION: RCP attenuated the rate of decay in SSEP amplitudes during
IACP. This suggested that RCP had a measurable physiologic effect on central
nervous system function and may increase the time that ACP can be safely
interrupted.
PMID- 9636904
TI - Anesthesia for deep hypothermic circulatory arrest in adults: experience with the
first 50 patients.
AB - OBJECTIVE: To evaluate the efficacy of a simple method of central nervous system
(CNS) protection in patients undergoing deep hypothermic circulatory arrest
(DHCA) lasting less than 30 minutes, for a variety of complex cardiovascular
procedures. DESIGN: A retrospective case review. SETTING: A university teaching
hospital. PARTICIPANTS: Fifty consecutive patients (25 women, 25 men) undergoing
elective or emergency cardiovascular operations requiring DHCA between August
1991 and December 1996. INTERVENTIONS: Patients underwent DHCA for a variety of
surgical procedures. Neurologic protection was with thiopental, ice packs to the
head, and systemic core hypothermia to a nasopharyngeal temperature (NPT) of 18
degrees to 20 degrees C. MEASUREMENTS AND MAIN RESULTS: The mean duration of
circulatory arrest was 18 +/- 10 minutes (range, 5 to 42 minutes). The mean NPT
at time of arrest was 18.7 degrees +/- 1.7 degrees C. Three patients (6%) had
gross CNS morbidity, one of whom died. The circulatory arrest times for these
three patients were 8, 39, and 40 minutes. Perioperative mortality was 8% (n =
4). The circulatory arrest times for the patients who died were 12, 13, 23, and
39 minutes. CONCLUSION: The anesthetic management of DHCA described is simple,
effective, and safe, and can be performed in any institution that performs
cardiac surgery.
PMID- 9636905
TI - Effect of aortic cannula characteristics and blood velocity on transcranial
doppler-detected microemboli during cardiopulmonary bypass.
AB - OBJECTIVES: Cerebral microemboli are responsible to a large extent for the
neuropsychiatric deficits after cardiac surgery. Differences in cannula size
during cardiopulmonary bypass (CPB) will result in different velocities of blood
exiting the aortic cannula. This study determined whether the number of
transcranial Doppler (TCD)-detected emboli in the middle cerebral artery (MCA)
during CPB correlated with blood speed or the direction of flow as determined by
the shape of the aortic cannula. DESIGN: Patients were studied prospectively for
evidence of TCD-detected emboli. If patients met the inclusion criteria, the
choice of cannula was determined by surgical preference. SETTING: All studies
were conducted at a single tertiary care academic cardiac surgery hospital by a
single observer. PARTICIPANTS: Thirty-two patients undergoing first-time elective
aortocoronary bypass surgery who were free of neurologic dysfunction or
peripheral vascular disease and weighed 60 to 85 kg were studied. Patients who
had other concurrent cardiac operations or who were in cardiogenic shock were
excluded. INTERVENTIONS: Three aortic cannula types for elective aortocoronary
bypass surgery were used: 24F curved (n = 19), 24F straight (n = 6), and 22F
straight (n = 7), with internal diameters (IDs) of 7.2, 6.6, and 5.9 mm,
respectively. TCD-detected emboli were identified in the MCA. MEASUREMENTS AND
MAIN RESULTS: The rate of TCD-detected emboli (0.02 to 11.4 emboli per minute)
was not related to the velocity of blood (46 to 77 cm/s) and was not affected by
the choice of either a straight or curved aortic cannula. CONCLUSIONS: The choice
of a straight or curved aortic cannula or of a 24F versus 22F cannula may not be
important with respect to the number of cerebral microemboli.
PMID- 9636906
TI - Cerebral complications after coronary artery bypass and heart valve surgery: risk
factors and onset of symptoms.
AB - OBJECTIVES: Cerebral complications continue to be a major cause of morbidity
after cardiac surgery. Earlier studies have mainly focused on intraoperative
events, but symptoms may also occur later in the postoperative period. The
purpose of this study was to determine the incidence and risk factors of focal
neurologic complications and timing of cerebral symptoms. DESIGN: A retrospective
study. SETTING: Linkoping University Hospital. PARTICIPANTS: Two thousand four
hundred eighty patients who underwent cardiac surgery from 1992 to 1995.
INTERVENTIONS: Standard cardiopulmonary bypass (CPB) technique was used in all
patients. Anticoagulant treatment included heparin and patients with coronary
artery surgery were also administered acetylsalicylic acid and valve-surgery
patients received warfarin or dicumarol. MEASUREMENTS AND MAIN RESULTS: Seventy
five patients (3%) had focal neurologic deficits and/or confusion
postoperatively. In 32 patients (43%), the onset was not intraoperative but
occurred later in the postoperative period. The lowest incidence of cerebral
complications was found in patients who underwent single-valve replacement (1.2%)
and the highest incidence was found in patients who underwent combined procedures
(valve and coronary artery surgery; 7.6%). Patients greater than 70 years of age
had a complication rate of 4.1% compared with 2.5% in patients aged 70 years and
less (p < 0.05). The incidence of diabetes mellitus was 11.4% in the entire
series, but was more common (18.7%; p < 0.05) in patients with cerebral symptoms.
Also, 5.9% of all patients had a history of cerebrovascular disease compared with
14.7% (p < 0.01) of patients with cerebral complications. CONCLUSION: Cerebral
complications may be delayed after cardiac surgery, suggesting causes of cerebral
damage other than intraoperative events. Valve-surgery patients had the lowest
incidence and patients with combined procedures had the highest incidence of
cerebral complications. Advanced age, diabetes mellitus, and preexisting
cerebrovascular disease increased the risk.
PMID- 9636907
TI - Intraoperative transesophageal echocardiography during noncardiac surgery.
AB - OBJECTIVE: To investigate the use and impact of transesophageal echocardiography
(TEE) during noncardiac surgery. DESIGN: Retrospective study. SETTING: A
university teaching hospital. PARTICIPANTS AND INTERVENTIONS: The medical records
and the videotapes of 123 intraoperative TEE examinations were reviewed.
MEASUREMENTS AND MAIN RESULTS: TEE was used for non-consultative indications in
68 patients and in consultation in 55 patients. Information that would not have
been detected intraoperatively by other means included intracardiac defects,
valvular and aortic pathology, the presence or absence of ventricular dysfunction
or intracardiac thrombi, and embolization during surgery. Findings during the
initial TEE examination and the TEE evaluation of intraoperative events resulted
in a major impact on patient management in 15% of patients. The majority of
patients in whom TEE had any impact (the sum of major, minor, and limited impact
groups) were classified as American Society of Anesthesiologists (ASA) class 3 or
4. Patients in whom TEE had any impact were significantly older than patients in
whom TEE had no impact (66.5 +/- 13.4 years v 58.1 +/- 16.2 years; p < 0.05). No
patient experienced a complication related to intraoperative TEE. CONCLUSION: It
appears that TEE in patients undergoing noncardiac surgery is efficacious in
rapidly disclosing new findings and information during periods of hemodynamic
instability. It may have a significant impact on intraoperative patient
management and may be beneficial in patients older than 66 years of age.
PMID- 9636908
TI - Simultaneous transesophageal atrial pacing and transesophageal echocardiography
in cardiac surgical patients.
AB - OBJECTIVES: To measure the effect of inserting a transesophageal echocardiography
(TEE) probe on the pacing threshold of a previously inserted transesophageal
pacing stethoscope, and to examine whether an indwelling pacing stethoscope
influences the feasibility and image quality of a TEE examination. DESIGN:
Prospective, open study using each patient as his/her own control. SETTING:
Cardiac operating room of an academic medical center. PARTICIPANTS: Twenty adult
patients in sinus rhythm and anesthetized for cardiac surgery. INTERVENTIONS:
After induction of anesthesia and endotracheal intubation, a pacing stethoscope
was inserted into the esophagus. A 5-MHz TEE probe was inserted to the four
chamber-view position. A full echocardiographic examination was performed, noting
image quality, ease of probe manipulation, and loss of pacing. The pacing
stethoscope was removed, and image quality assessed again. MEASUREMENTS AND MAIN
RESULTS: The initial mean pacing threshold +/- 1 standard deviation (SD) was 19
+/- 8 mA (range, 10 to 37 mA). After placement of the echocardiography probe, the
mean threshold had increased to 24 +/- 8 mA (range, 11 to 40 mA; p < 0.01). Loss
of pacing with probe manipulation was noted in 15 of 20 patients (transient in 10
patients, permanent in 5 patients). Problems manipulating the probe because of
sticking to the pacing stethoscope were noted in 10 of 20 patients. Poor image
quality, resolving after stethoscope removal, was seen in two patients.
CONCLUSION: Placement of a TEE probe results in a modest increase of the
transesophageal pacing threshold. An indwelling pacing stethoscope frequently
interferes with the ability to perform a full echocardiographic examination, and
probe manipulation commonly causes loss of pacing.
PMID- 9636909
TI - Short atrioventricular delay dual-chamber pacing early after coronary artery
bypass grafting in patients with poor left ventricular function.
AB - OBJECTIVE: To investigate the effect of short atrioventricular (AV) delay dual
chamber pacing on mean arterial pressure (MAP) and stroke volume index (SVI) in
patients with poor left ventricular (LV) function after cardiac surgery. DESIGN:
A prospective study. SETTING: A university hospital, single-center study.
PARTICIPANTS: The study group consisted of 20 patients aged 63 +/- 9 years with a
left ventricular ejection fraction (LVEF) less than 30%. The control group
consisted of 20 patients aged 61 +/- 10 years, with an LVEF greater than 50%.
INTERVENTIONS: Immediately after routine coronary artery bypass grafting (CABG)
the AV delay was shortened from 160 to 40 milliseconds in atrial-paced (DDD) mode
and from 100 to 40 milliseconds in atrial-sensed ventricular stimulation (VDD)
mode. MAP was on-line monitored and SVI was calculated by thermodilution. In one
patient with an LVEF of 18% (case study), transmitral flow velocity and LV
isovolumetric relaxation time were assessed using Doppler echocardiography during
VDD pacing at 40-, 80-, and 120-millisecond AV delay. RESULTS: Short-AV delay DDD
pacing decreased MAP in the control group (84.3 +/- 9 v 75.7 +/- 9 mmHg; p <
0.05) and SVI in both groups (study group, 35.9 +/- 7 v 31.7 +/- 7 mL/m2; control
group, 35.3 +/- 6 v 31.0 +/- 6 mL/m2; p < 0.05). Shortening the AV delay had no
influence on MAP and SVI during VDD pacing. During the echocardiographic case
study, AV delay shortening distinctly modified ventricular filling patterns.
Optimal LV filling and transmitral flow were achieved with an intermediate AV
delay of 80 milliseconds. CONCLUSION: Dual-chamber pacing with nonphysiologic
short AV delay failed to improve acute hemodynamics in patients with poor LV
function after CABG. Short AV delay VDD pacing was superior to DDD pacing in both
normal and impaired LV function. The use of Doppler echocardiography enabled
optimization of the AV delay on the basis of LV filling patterns.
PMID- 9636910
TI - Cardiac troponin I in diagnosis of perioperative myocardial infarction after
cardiac surgery.
AB - OBJECTIVE: The diagnosis of perioperative myocardial infarction (PMI) after
cardiac surgery remains an important issue. The present study was designed to
determine the relevance of the measurement of serum cardiac troponin I (cTnI, a
biochemical marker with high cardiospecificity. Therefore, cTnI was compared with
creatine kinase-MB (CK-MB) mass and to the other classical signs of myocardial
infarction after cardiac surgery. DESIGN: A prospective study. SETTING: A
university hospital. PARTICIPANTS: Forty-one patients undergoing coronary artery
bypass grafting (CABG) (n = 17) or valvular replacement (n = 24). These patients
were separated into three groups according to postoperative complications: group
1, Q-wave PMI (n = 5); group 2, nonspecific changes (non-Q wave) on the
electrocardiogram (ECG) and/or need of inotropic support (n = 12); group 3, no
postoperative complication (n = 24). INTERVENTIONS: Postoperative follow-up
consisted of serial determination of different biochemical markers (CK, CK-MB,
cTnI), ECGs, and echocardiography. Blood samples were drawn before (H0) and 3
(H3), 12 (H12), 20 (H20), 24 (H24), and 48 (H48) hours after the onset of
cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: In all patients in
group 3, CK-MB and cTnI concentrations increased, and peaked at H12 after CPB
(13.4 +/- 7.7 and 7.1 +/- 4.1 micrograms/L for CK-MB and cTnI, respectively). In
group 1, cTnI concentrations were significantly higher than in group 3 from H12
until H48 (p < 0.002), peaked later (H24; 59.0 +/- 38.8 micrograms/L), and
remained in plateau. In group 2, cTnI peak concentrations were significantly
different than in groups 1 and 3 (26.2 +/- 14.8 micrograms/L) and occurred at H24
(as in patients with Q-wave PMI). CONCLUSION: A cTnI concentration less than 15
micrograms/L (mean + 2 standard deviations [SDs] of peak cTnI in group 3) within
24 to 48 hours after cardiac surgery is highly suggestive of the absence of
perioperative myocardial necrosis. Because of its higher cardiospecificity than
CK-MB mass, and its prolonged release after myocardial necrosis, cTnI might be a
useful tool in the diagnosis of PMI after cardiac surgery.
PMID- 9636911
TI - Low-dose heparin appears safe and can eliminate protamine use for carotid
endarterectomy.
AB - OBJECTIVE: To determine the morbidity associated with carotid endarterectomy
(CEA) when low doses of heparin (30 U/kg) are used for anticoagulation. This
technique eliminates the need for protamine and its potentially deleterious
effects on some patients. DESIGN: A retrospective chart review. SETTING: A large
academic medical center. PARTICIPANTS: The records of 420 consecutive CEAs in 337
patients (83 bilateral procedures). INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: The amount of heparin used was less than that used in most reported
studies. Eighty-two percent of patients received only 2,000 U of heparin for
their entire operation (range, 500 to 3,000 U). Complication rates were low.
Neurologic complications included a 0.95% incidence of nonfatal stroke and a 2.1%
incidence of transient neurologic deficits that resolved in the first day. There
was no mortality. The wounds were described in the postoperative period as dry
(96%), swollen (3%), or bloody (1%). No patients received protamine. CONCLUSION:
The use of 5 to 10,000 U of heparin will provide anticoagulation for more than an
hour. In CEA surgery, anticoagulation for this duration is often unnecessary. A
smaller dose of heparin (30 U/kg) can provide adequate anticoagulation for this
procedure while eliminating the potentially deleterious effects of protamine use.
No additional morbidity was attributed to this technique.
PMID- 9636912
TI - Heparin-coated bypass circuits (Carmeda) suppress the release of tissue
plasminogen activator during normothermic coronary artery bypass graft surgery.
AB - OBJECTIVES: To study fibrinolysis in a homogeneous first-time coronary artery
bypass surgery (CABG) population in whom heparin-coated circuits were used.
DESIGN: A prospective, blinded, randomized, placebo-controlled study. SETTING: A
university hospital, tertiary care, intraoperative and postoperative intensive
care unit. PARTICIPANTS: Twenty-one adult elective primary CABG patients.
INTERVENTIONS: Randomized circuit-type centrifugal pump, membrane oxygenator,
rigid cardiotomy reservoir, either placebo (n = 10) or heparin-coated (n = 11)
(Carmeda; Medtronic Inc., Anaheim, CA). MEASUREMENTS AND MAIN RESULTS: Blood
samples were analyzed for tissue plasminogen activator (TPA) activity, TPA
antigen, plasminogen activator inhibitor-1 (PAI-1) activity, prothrombin complex
F1.2, and antithrombin III (AT-III) at the following times: before
cardiopulmonary bypass (CPB), during CPB (30 and 60 minutes), post-CPB, and day 1
postsurgery. TPA activity and antigen increased fivefold in the placebo group
during CPB, whereas it did not even double in the heparin-coated group. PAI-1,
F1.2, and AT-III were not different between groups. CONCLUSIONS: Heparin-coated
CPB circuits reduced TPA release in this homogeneous CABG population with routine
heparin/protamine management.
PMID- 9636913
TI - Thromboelastography with heparinase in orthotopic liver transplantation.
AB - OBJECTIVE: To investigate the role of heparin in the postreperfusion coagulopathy
during liver transplantation with heparinase-guided thromboelastography. DESIGN:
A prospective, interventional study. SETTING: A university-affiliated hospital.
PARTICIPANTS: Twenty-six patients undergoing orthotopic liver transplantation
(OLT). INTERVENTIONS: Blood drawn at five intervals for thromboelastography
assessment with native (12 patients) or celite blood (14 patients) compared with
simultaneous thromboelastography traces with added heparinase. MAIN RESULTS: In
the native samples, the prolonged R (reaction) and K (coagulation) time and
decreased alpha angle were corrected in heparinase thromboelastograph traces
immediately before reperfusion and 10 minutes postreperfusion. In the celite
accelerated samples, the heparinase traces showed correction of the R and K times
and alpha angle only at the 10-minute postreperfusion stage. In seven patients
who had thromboelastography performed after protamine administration, there were
no differences between celite and heparinase-celite traces. CONCLUSIONS:
Heparinase-treated thromboelastography offered compelling evidence for the
presence of heparin-like activity after liver graft reperfusion. The objective
evidence provided by this modification of thromboelastography-guided protamine
administration and was useful in identifying one of the many potential causes of
postreperfusion bleeding in patients undergoing OLT.
PMID- 9636914
TI - The importance of sampling site in the measurement of whole-blood platelet flow
cytometry.
AB - PURPOSE: Flow cytometry is an emerging technology that may be of use in
clarifying the defects of platelet function after cardiopulmonary bypass.
However, the technique used for platelet sampling may affect results. The
objective of this study was to evaluate the influence of the sampling site on the
degree of expression of a variety of platelet-associated proteins. METHODS: Whole
blood flow cytometric assays for the detection of platelet glycoprotein (GP) Ib,
guanosine monophosphate (GMP)-140, thrombospondin, activated GPIIb/IIIa, and
platelet-associated factor (FXIIIa) were developed. These markers were then
measured in samples taken simultaneously from a peripheral vein, radial artery,
and the side port of the central venous catheter, in eight patients about to
undergo surgery. RESULTS: When multiple samples from individual patients were
assessed, the degree of activation with all of the activation assays (GMP-140,
thrombospondin, activated GPIIb/IIIa, FXIIIa) was significantly greater in
samples taken from the arterial catheter (p < 0.05) compared with the central
venous catheter or the peripheral vein. The mean difference between sample sites
was calculated in the study patients. Percent activation of FXIIIa from arterial
blood was significantly greater than from the central vein and the peripheral
vein (arterial-peripheral venous, 18.7 +/- 8.6; central venous-peripheral venous,
3.7 +/- 3.6; p = 0.005). There was no site-related difference in detected
expression of platelet GPIb. CONCLUSION: The site of platelet sampling
significantly affects the degree of activation detected by flow cytometry. To
approximate results that would be obtained from peripheral blood, samples should
be taken from the side port of the central venous catheter and not from the
arterial catheter in patients studied during surgery.
PMID- 9636915
TI - Splenic laceration associated with transesophageal echocardiography.
PMID- 9636916
TI - Esmolol resistance during anesthesia for thoracoscopically assisted coronary
artery bypass grafting.
AB - The anesthetic technique for two patients who underwent thoracoscopic harvesting
of the LIMA followed by a mini-thoracotomy for surgical myocardial
revascularization of isolated LAD artery stenosis is reported. Both patients
unexpectedly showed esmolol resistance during anastomosis of the LIMA to the LAD
artery. However, excellent graft patency, early extubation, and rapid recoveries
were achieved.
PMID- 9636917
TI - Persistent intraoperative hypotension as a presentation of bilateral subclavian
artery stenosis.
PMID- 9636918
TI - Preoperative valvuloplasty in a thermally injured patient with critical aortic
stenosis.
PMID- 9636919
TI - Refractory vasodilation after cardiopulmonary bypass for heart transplantation in
recipients on combined amiodarone and angiotensin-converting enzyme inhibitor
therapy: a role for vasopressin administration.
PMID- 9636920
TI - Quantifying risk and assessing outcome in cardiac surgery.
AB - Quality improvement, research, and reporting of outcome results can be stratified
by preoperative risk by using a logistic regression equation or scores to correct
for multiple risk factors. The more than 30-fold mortality differences between
lowest and highest risk patients make it critical to stratify outcome results by
patient severity. Probabilities are not predictions, however, and caution must be
exercised when applying scores to individuals. Outcome assessment will grow in
its importance to professionals, initially in the guise of quality reporting and
improvement, but increasingly as a tool for risk assessment, patient counseling,
and directing therapeutic decisions based on more complete information about
patient subgroups. Physicians may be called on for recommendations in choosing
systems for their hospitals and communities. Therefore, it is important to have
an understanding of how such systems are developed, what factors indicate
adequate performance of a system, and how such systems of risk stratification
should be applied in practice.
PMID- 9636921
TI - Monitoring of brain function during carotid endarterectomy: an analysis of
contemporary methods.
PMID- 9636922
TI - Computer technology for the anesthesiologist: cardiothoracic and vascular
anesthesia on the Internet.
PMID- 9636923
TI - CASE 3--1998. Pulmonary reperfusion edema associated with pulmonary
thromboendarterectomy.
PMID- 9636924
TI - Pro: during cardiopulmonary bypass for elective coronary artery bypass grafting,
perfusion pressure should routinely be greater than 70 mmHg.
PMID- 9636925
TI - Con: during cardiopulmonary bypass for elective coronary artery bypass grafting,
perfusion pressure should not routinely be greater than 70 mmHg.
PMID- 9636926
TI - Evaluation of a hemodynamic tracing.
PMID- 9636927
TI - Off-axis view using a multiplane transesophageal echocardiography probe
facilitates cannulation of the coronary sinus.
PMID- 9636928
TI - Comparison of pulsatile versus nonpulsatile perfusion on the postcardiopulmonary
bypass aortic-radial artery pressure gradient.
PMID- 9636930
TI - Hepatitis A in waste water treatment plant workers: is vaccination necessary?
PMID- 9636929
TI - Occupational and environmental medicine in the family medicine curriculum.
PMID- 9636931
TI - Can corrective lenses effectively improve a color vision deficiency when normal
color vision is required?
PMID- 9636932
TI - Symptoms in 18,495 Persian Gulf War veterans. Latency of onset and lack of
association with self-reported exposures.
AB - Toxic or environmental exposures have been suggested as a possible cause of
symptoms reported by Gulf War veterans. To further explore this hypothesis, we
analyzed findings in 18,495 military personnel evaluated in the Department of
Defense Comprehensive Clinical Evaluation Program. The program was established in
1994 to evaluate Persian Gulf veterans eligible for Department of Defense medical
care who had health concerns after service in the Persian Gulf during Operation
Desert Shield/Desert Storm. The evaluation included a structured clinical
assessment, a physician-administered symptom checklist, and a patient
questionnaire addressing self-reported exposures, combat experiences, and work
loss. Among 18,495 patients examined, the most common symptoms were joint pain,
fatigue, headache, memory or concentration difficulties, sleep disturbances, and
rash. Symptom onset was often delayed, with two-thirds of symptoms not developing
until after individuals returned from the Gulf War and 40% of symptoms having a
latency period exceeding one year. There was no association between individual
symptoms and patient demographics, specific self-reported exposures, or types of
combat experience. Increased symptom counts were associated with work loss, the
number of self-reported exposures, the number of types of combat experience, and
certain ICD-9 diagnostic categories, particularly psychological disorders.
Prolonged latency of symptom onset and the lack of association with any self
reported exposures makes illness related to toxic exposure less likely.
PMID- 9636933
TI - Low response in white blood cell DNA adducts among workers in a highly polluted
cokery environment.
AB - Coke oven workers are often heavily exposed to polynuclear aromatic hydrocarbons
(PAHs); this exposure has been associated with higher cancer rates among these
workers. We assessed the exposure of cokery workers in an oil shale processing
plant. Personal hygienic monitoring, measurement of urinary 1-hydroxypyrene (1
OHP), and analysis of PAH-DNA adducts in white blood cells (WBCs) were performed.
The 32P-postlabeling method was used for adduct measurement. The mean adduct
value, 1.6 adducts per 10(8) nucleotides, did not differ significantly from the
control value (P = 0.098). Smokers had significantly higher adduct levels than
non-smoking workers (P = 0.002). 1-OHP levels measured in post-shift samples
correlated with DNA adducts found in white blood cells (WBCs). We conclude that
hygienic monitoring and measurement of urinary metabolites are essential
background exposure data when the biologically effective dose of chemical
carcinogens is assessed.
PMID- 9636934
TI - Differences between descriptive and multivariate estimates of the impact of
Chevron Corporation's Health Quest Program on medical expenditures.
AB - This investigation focused on alternative methods for evaluating the impact of
Chevron Corporation's Health Quest Fitness Center program on medical
expenditures, comparing descriptive and multivariate research designs. Many
uncontrolled studies of corporate health management programs base estimates of
program effectiveness on descriptive analyses such as Student's tests. Unlike
more sophisticated multivariate analyses, descriptive analyses often produce
biased estimates of program cost savings. To test alternative research design
methods, the investigators compared inpatient and pharmacy expenditures for
program participants and non-participants over a 2.5-year period, using
descriptive and multivariate regression analyses. Results showed that compared
with non-participants, expenditures for participants were significantly lower for
subjects who used a Health Quest fitness center at least twice weekly. Previous
descriptive studies suggested a much broader impact. The results underscore the
need to use multivariate analyses when evaluating the financial impact of
corporate health management programs, especially when randomization cannot be
used to assign participation status.
PMID- 9636936
TI - Prevalence and incidence of stenosing flexor tenosynovitis (trigger finger) in a
meat-packing plant.
AB - The purpose of this study was to determine the prevalence and incidence of
trigger finger (TF) in a meat-packing plant and explore the relationship between
hand-tool use and the development of TF. A cross-sectional study was competed
wherein 665 workers were interviewed and examined to determine the point
prevalence. Subsequently, 454 TF-negative workers were followed up and examined
twice at a median interval of 225 days. The point prevalence of TF was 14%. The
person-year incidence rate was 12.4% and 2.6% for tool use and non-tool use
workers, respectively. Forty-three cases of TF (75.2%) in the incidence arm of
the study used a hand tool, for a relative risk of 4.7 (P < 0.002; 95% confidence
interval, 1.5-23.9). Although a significant relationship was found between
ethnicity and the presence of TF in the prevalence data, this was not confirmed
in the incidence study. There is an increased prevalence of TF in this meat
packing plant and high worker turnover may underestimate the true prevalence
rates. Hand-tool use increases the risk of developing TF.
PMID- 9636935
TI - Occupational upper extremity disorders in the federal workforce. Prevalence,
health care expenditures, and patterns of work disability.
AB - Upper extremity disorders (UEDs) account for a significant number of work-related
illnesses in the US workforce. Little information exists on the distribution of
UEDs, their associated health care and indemnity costs, or patterns of work
disability. The study presented is an analysis of upper extremity claims within
the federal workforce. In this study, the universe consisted of all claims
accepted by the US Department of Labor, Office of Workers' Compensation Programs
(OWCP), from October 1, 1993, through September 30, 1994. A total of 185,927
claims of notices of injury were processed during the study period, and of these,
8,147 or 4.4% had an UED diagnosis coded according to the International
Classification of Diseases, Clinical Modification (ICD-9-CM). 5,844 claims
involved a single UED diagnosis and were the only claims field by these employees
between October 1, 1990, and September 30, 1994. These single claims with single
diagnoses comprised the sample for further analysis. Mononeuritis and
enthesopathies of the upper limb were the most common diagnoses, accounting for
43% and 31% of the claims, respectively. Women had a higher proportion of carpal
tunnel syndrome, "unspecified" mononeuritis, and "unspecified" enthesopathies.
The majority of claimants for both the mononeuritis- and enthesopathy-related
diagnoses were between 31 and 50 years of age, received only health care
benefits, and did not incur wage loss. Health care costs for mononeuritis and
enthesopathy claims were $12,228,755 (M = $2,849). Carpal tunnel syndrome (CTS)
and enthesopathy of the elbow were the most costly diagnoses, accounting for 57%
and 16% of the total, respectively. Surgical services represented the highest
expenditures in CTS claims. Physical therapy accounted for the majority of health
care costs for enthesopathy cases. The mean number of workdays lost for CTS and
enthesopathy claims were 84 and 79, and the average indemnity costs were $4,941
and $4,477, respectively. These findings indicate that while UEDs represent a
relatively small percentage of all workers' compensation cases, the health care
and indemnity costs are considerable. Also mean duration and pattern of work
disability revealed that these disorders can result in chronic work disability
similar to that observed in low back pain. The results highlight the need to
determine whether interventions that account for the majority of costs
significantly impact long-term outcomes. There is also a need to identify risk
factors for prolonged disability in those who experience problems with delayed
recovery.
PMID- 9636937
TI - Non-fatal workplace violence workers' compensation claims (1993-1996).
AB - More is known about fatal workplace violence than non-fatal workplace violence
(NFWV). This study provides descriptive information on the number and cost of
NFWV claims filed with a large workers' compensation carrier. NFWV claims from 51
US jurisdictions were selected either by cause codes or by word search from the
accident-description narrative. Claims reported in 1993 through 1996 were
analyzed to report the frequency, cost, gender, age, industry, and nature of
injury. An analysis of a random sample of 600 claims provided information on
perpetrator type, cause of events, and injury mechanism. A total of 28,692 NFWV
claims were filed during the study period. No cost was incurred for 32.5% of the
claims, and 15.5% received payments for lost work. As a percentage of all claims
filed by industry, schools had the highest percentage (11.4%) of NFWV claims, and
banking had the highest percentage (11.5%) of cost. The majority of claims in the
banking random sample group (93%) were due to stress. In the random sample, 90.3%
of claims were caused by criminals (51.8%) or by patients, clients, or customers
(38.5%). Only 9.7% were caused by an employee (9.2%) or a personal acquaintance
of the employee (0.5%). Employers should acknowledge that NFWV incidents occur,
recognize that the majority of perpetrators are criminals or clients rather than
employees, and develop appropriate prevention and intervention programs.
PMID- 9636938
TI - Comparison of workers' compensation costs for two cohorts of injured workers
before and after the introduction of managed care.
AB - A comprehensive safety and managed care initiative was instituted in 1991 at a
large self-insured medical center in an effort to reduce workers' compensation
costs. It features an on-site case management team, a preferred provider
organization, and safety engineering efforts and ergonomic controls used
proactively to aggressively identify and abate workplace hazards. Two worker
populations were followed up longitudinally for three years before and after the
initiative. Costs incurred by each cohort were compared. A 50% reduction in total
expenditures was seen in the managed care cohort. The hospital component of the
system saw a decrease in compensation of 62% for temporary total disability and
38% for permanent partial disability. Medical expenditures decreased 50%.
Dramatic reductions in costs are achievable, without compromising quality of
care, when managed care principles and safety efforts are emphasized.
PMID- 9636939
TI - Risk of job-related injury among construction laborers with a diagnosis of
substance abuse.
AB - This study attempts to determine whether a diagnosis of substance abuse among
construction laborers is associated with an increased risk of work-related
injuries. Records for construction laborers in Washington State who were covered
by health insurance through the local union were matched against workers'
compensation records in the Washington State Department of Labor and Industries.
Using the health insurance records, we identified those who had a diagnosis of
substance abuse during the two-year period 1990-1991. Using the workers'
compensation records, we were then able to compare injury rates for those with
substance abuse diagnoses with the rates for those without such diagnoses. The
total cohort consisted of 7,895 laborers. Among the 422 who had a substance abuse
diagnosis, the rate of time-loss injuries per 100 full-time equivalent workers
was 15.1, compared with 10.9 among the remainder of the cohort. Most of the
difference appeared in the 25-34-year age group, in which the rate of injury per
100 full-time equivalent workers was 23.6 for substance abusers, compared with a
rate of 12.2 for non-substance abusers, for a statistically significant relative
risk of 1.93. The study suggests that younger workers might be an appropriate
target for interventions aimed at reducing the level of substance abuse as a way
of preventing injuries on the job. Studies by others have indicated some degree
of success in this direction through the use of employee assistance programs in
which the worker is referred to specific programs or providers for treatment. The
state legislature in Washington has recently passed legislation providing
incentives for the use of employee assistance programs. More effort is needed,
however, to evaluate the effectiveness of such programs.
PMID- 9636940
TI - Schizophrenia-specific basic symptoms. A successful replication.
AB - Several investigations showed that the Frankfurt Complaint Questionnaire (FCQ)
has no diagnostic specificity. However, in a preceding study two new FCQ
subscales were developed: FCQ-S, sensitive to schizophrenia, and FCQ-A, sensitive
to alcoholism. The aim of the present study was to replicate the diagnostic
sensitivity of those subscales. Four groups were considered: schizophrenics with
marked negative symptoms (n = 25); schizophrenics with no or mild negative
symptoms (n = 25); alcoholics (n = 25); patients with obsessive-compulsive
disorder (n = 15). FCQ original subscales and total score did not differ between
groups. As expected, in FCQ-S both schizophrenic groups had significantly higher
scores than the other groups; FCQ-A failed to show group differences but was
significantly related to alcoholism markers.
PMID- 9636941
TI - Symptom structure in schizophrenia: two-, three- or four-factor models?
AB - Beside the syndromic dichotomy (negative-positive), other symptomatic dimensions
have been described in schizophrenia. A question of interest is, therefore, to
know which symptom structures can be individualized to characterize
schizophrenia. Using confirmatory factor analysis in 135 patients, a two-factor
model (negative-positive), a three-factor model (negative-positive
disorganization) and a four-factor model (negative-positive-disorganization
relational) were primarily identified with SANS (Scale for the Assessment of
Negative Symptoms) and SAPS (Scale for the Assessment of Positive Symptoms). In
contrast, no models could be identified with PANSS (Positive and Negative
Syndrome Scale). The results confirm the relevance of other syndrome dimensions,
beside the negative and positive ones and suggest that SANS-SAPS was more useful
than PANSS in identifying an adequate dimensional factor structure of
schizophrenic symptoms.
PMID- 9636942
TI - Disturbance of consciousness due to methamphetamine abuse. A study of 2 patients.
AB - The present paper reports 2 cases of methamphetamine abuse. Following consecutive
methamphetamine administration, the patients developed acute intoxication, during
which time they showed a unique type of disturbance of consciousness: delirium
and twilight state. In both cases, mental status changed, passing through three
distinct stages: restlessness and insomnia, hallucinatory paranoid state, and
disturbance of consciousness. A review of the literature suggests that
disturbance of consciousness may occur occasionally during the course of
amphetamine and methamphetamine intoxication, although these symptoms can be
overlooked easily due to confounding symptomatology.
PMID- 9636943
TI - Psychopathological assessment and diagnosis. A study of specificity of single
symptoms.
AB - The importance of single symptoms in the diagnostic process has not been
adequately studied, mainly because of the complexity of the information involved.
The aim of the present study is to investigate the interconnection between
psychopathological assessment and diagnostic classification, with the aid of a
nonparametric, inductive pattern recognition method. Using the concept of
inductive logic and a theory of inductive knowledge acquisition, a model has been
developed to describe psychopathological assessment and diagnostic
classification. Based on a comprehensive psychopathological assessment in 837
patients with 14 different diagnoses, classification values were calculated for
specific symptoms in different diagnostic groups. Furthermore, nonparametric
statistical procedures have advantages over discriminant analytic approaches:
more information is utilized in differentiating the groups and differentiations
can be made between more groups, whereby the rate of correctly classified cases
is comparable with discriminant analytic approaches. The pattern recognition
method appears to illustrate the multidimensional, medical decision-making in a
comprehensible way.
PMID- 9636944
TI - Adolescent ballet school students: their quest for body weight change.
AB - Body mass index (BMI) and body type of female and male adolescent ballet dancers
(n = 90) and school students (n = 156) were determined. Participants were asked
for the body weight she or he would prefer, and ballet students were administered
the Eating Attitudes Test-40 (EAT-40). Results between age groups and with
reference values were compared. Both in dancers and controls, girls wanted to
lose more body weight than boys, with female ballet dancers more than female
controls. The desire for reducing body weight was expressed by female ballet
dancers of all BMI percentiles and body types, with the highest difference
between real and desired body weight in 11-, 13-, and 16-year-olds. In the other
groups, a quest for lower body weight was expressed only by adolescents of higher
BMI and pyknomorphic and/or mesomorphic body type. Female ballet dancers of all
age groups sought to reach body weights below the 5th percentile or below 82% of
normal body weight. Desired body weight change was influenced by BMI and body
type and correlated positively with EAT-40 score.
PMID- 9636945
TI - On the validity of the Beck Depression Inventory. A review.
AB - The present review discusses validity aspects of the Beck Depression Inventory
(BDI) on the basis of meta-analyses of studies on the psychometric properties.
Shortcomings of the BDI are its high item difficulty, lack of representative
norms, and thus doubtful objectivity of interpretation, controversial factorial
validity, instability of scores over short time intervals (over the course of 1
day), and poor discriminant validity against anxiety. Advantages of the inventory
are its high internal consistency, high content validity, validity in
differentiating between depressed and nondepressed subjects, sensitivity to
change, and international propagation. The present paper outlines agreements and
contradictions between the various studies on the BDI and discusses the potential
factors (composition of the subject sample, statistical procedures, point in time
of measurement) accounting for the variance in their results. The Beck Depression
Inventory (BDI) is world-wide among the most used self-rating scales for
measuring depression. Since the test construction in 1961, the test has been
employed in numerous (more than 2,000) empirical studies. The present review will
only consider those investigations which are primarily concerned with the
validity or the psychometric properties of the BDI. Since most studies are
oriented along the criteria of the classical test theory, our review will discuss
to what extent the BDI meets these criteria.
PMID- 9636946
TI - Disordered differentiation of memory T cells in rheumatoid arthritis.
PMID- 9636947
TI - Aspiration and injection of joints.
PMID- 9636948
TI - Joint manifestations in Behcet's disease. A review of 340 cases.
AB - OBJECTIVES: To gain additional knowledge on the joint manifestations of Behcet's
disease, with special attention to unusual forms. PATIENTS AND METHODS:
Retrospective review of 340 cases with joint manifestations identified among 601
cases of Behcet's disease seen over a 15-year period. All the patients met
International Study Group for Behcet's disease criteria. Radiographs of all
joints with arthritis were obtained. Starting ten years ago, a radiograph of the
sacroiliac joint was taken routinely. RESULTS: Joint manifestations were present
in more than half the patients (56.57%) and were inaugural in 18.23% of cases.
The knees and ankles were the joints most commonly affected. Monoarthritis and
oligoarthritis were seen in 16.17% and 11.76% of cases, respectively and
polyarthritis involving the large limb joints and the small joints of the hands
and feet in 17.05% of cases. Unusual forms included polyarthritis with
deformities and/or destruction (n: 8, including two patients who also met
criteria for rheumatoid arthritis), pseudogout (n: 5), popliteal cyst (n: 3,
including one case imitating deep vein thrombosis), myositis (n: 1),
spondylarthropathy (n: 5), and Sjogren's syndrome (n: 2). Children were more
likely than adults to have joint manifestations (73.68%) and polyarthritis
(35.7%). CONCLUSION: Joint manifestations are common in Behcet's disease. Their
unusual forms deserve to be known since they can raise diagnostic problems when
they are inaugural.
PMID- 9636949
TI - Rheumatoid arthritis in Congo-Brazzaville. A study of thirty-six cases.
AB - OBJECTIVES: To define the epidemiology, clinical features and outcomes of
rheumatoid arthritis in a hospital-based population in Congo-Brazzaville.
PATIENTS AND METHODS: We retrospectively reviewed the medical records of the 36
subjects seen on an inpatient or outpatient basis at our rheumatology department
who met American College of Rheumatology criteria for rheumatoid arthritis.
RESULTS: There were 28 women and eight men (male to female ratio, 0.28), with a
mean age of 43.5 years. The total number of patients seen at our department
during the study period was 3518, yielding a prevalence of 1% for rheumatoid
arthritis. Seven per cent of the patients with inflammatory joint disease had
rheumatoid arthritis. Mean disease duration was 9.5 years (range, 1-25 years).
The onset was gradual in every case and distal joints were affected first in 33
patients. All the patients but one had bilateral symmetric polyarthritis;
affected joints included the proximal interphalangeal joints (n: 33), the
metacarpophalangeal joints (n: 27), the wrists (n: 27), the metatarsophalangeal
joints (n: 20), the knees (n: 26), the elbows (n: 18), the hips (n: 4), the
temporomandibular joints (n: 4), and the cervical spine (n: 5). Boutonniere
deformity of the fingers was the most common joint deformity (n: 15), followed by
ulnar drift (n: 9). Three patients had tenosynovitis, two had tendon rupture, one
had carpal tunnel syndrome and one had rheumatoid nodules. Rheumatoid factors
were found in 70% of cases. Evidence of chondrolysis was seen on roentgenograms
in every case. Gold and chloroquine were the two most commonly used second-line
agents. Seven patients were on prednisone, in a mean daily dose of 6 mg. Mean
follow-up was 15 months (range: 3-36 months). Steinbrocker's disease activity
stage was IV in 14 patients and III in eight patients; Steinbrocker's functional
stage was IV in five patients and III in three. CONCLUSION: The features and
outcomes of rheumatoid arthritis in Congo-Brazzaville match textbook descriptions
except for a lower prevalence of extraarticular manifestations. Similar findings
have been reported for East Africa, South Africa, and some countries of West
Africa.
PMID- 9636950
TI - Adhesive capsulitis of the shoulder: an open study of 40 cases treated by joint
distention during arthrography followed by an intraarticular corticosteroid
injection and immediate physical therapy.
AB - OBJECTIVE: To evaluate the short- and long-term efficacy of joint distention
during arthrography followed by an intraarticular corticosteroid injection then
by high-intensity physical therapy and use of an abduction splint in an open
study of 40 patients with adhesive capsulitis of the shoulder. METHODS: Patients
were evaluated on D0, D5 (i.e., before discharge) and D30 for pain severity
assessed using a four-point scale (0-3) and for passive ranges of abduction,
internal rotation and external rotation of the shoulder. RESULTS: Mean pain
severity improved significantly from 2.18 +/- 0.6 (mean +/- SD) on D0 to 1.74 +/-
0.5 on D5 (P: 0.01) and 0.92 +/- 0.5 on D30 (P: 0.02). Passive range of abduction
increased significantly from 44.8 degrees +/- 1.54 degrees on D0 to 68 degrees +/
15 degrees on D5 (P: 0.05), whereas the difference between D5 and D30 (71
degrees +/- 13 degrees) was not significant (P: 0.8). Similarly, passive range of
external rotation increased significantly from 4.3 degrees +/- 0.6 degree on D0
to 13.5 degrees +/- 0.5 degree on D5 (P = 0.04) and showed a nonsignificant
increase from D5 to D30 (17 degrees +/- 13 degrees, P: 0.2). CONCLUSION: Joint
distention during arthrography followed by an intraarticular corticosteroid
injection then by high-intensity physical therapy significantly improved pain and
passive range of motion within the first five days, and these gains were
sustained after one month.
PMID- 9636951
TI - Conservative inhospital management of low back pain patients. Factors predicting
two-year outcomes.
AB - OBJECTIVE: To evaluate the course of symptoms and occupational outcomes in low
back pain patients two years after conservative inhospital therapy. METHODS:
Retrospective medical chart study of all patients admitted to a rheumatology
department in Geneva in 1993, and telephone interview two years after the
admission. RESULTS: Eighty of the 99 patients (81%) identified by the chart
review were interviewed by telephone. The course of symptoms (evaluated based on
subjective assessments and on the number of subsequent admissions) was similar in
the patients who had acute (n = 33) and chronic (n = 47) low back pain at the
index admission. Patients who had not returned to work were significantly more
likely to report persistent pain (P < 0.001). As many as 61% of patients had not
resumed work. Sick leave duration and symptom duration at admission were the
factors that had the largest effects on prognosis. Over 90% of patients who were
put on sick leave for more than four weeks did not return to work. Permanent
cessation of work was recorded in 82% of manual laborers versus 27% of patients
in sedentary jobs (P < 0.001). CONCLUSION: Our results are ascribable, at least
in part, to the fact that our population included large numbers of patients with
persistent pain and of blue collar workers with physically-challenging jobs. Sick
leave duration and occupation were the best predictors of the course of symptoms
and work status.
PMID- 9636952
TI - Lean tissue mass is a better predictor of bone mineral content and density than
body weight in prepubertal girls.
AB - PURPOSE AND METHODS: Body weight is the most extensively studied correlate of
bone mass and is widely used as a covariate in statistical evaluations of bone
mineral parameters. Lean tissue mass (LTM) also correlates with bone mass. We
evaluated the correlations linking each of these two parameters with bone mineral
content and bone mineral density in 41 prepubertal girls, including ten swimmers,
18 gymnasts and 13 nonathletes. Lean tissue mass, bone mineral content and bone
mineral density were measured using dual-energy X-ray absorptiometry (Hologic QDR
1000/W; Hologic Inc., Waltham, MA, USA). Forward stepwise multiple regression was
used to evaluate correlations linking bone mineral content or density (the
dependent variables) to body weight or lean tissue mass (the independent
variables). RESULTS: Body weight and lean tissue mass showed strong correlations
with all bone mineral content and density measurements in the simple linear
regression analysis, with lean tissue mass yielding the highest Pearson's
correlation coefficients. In the multiple regression model, lean tissue mass
consistently explained the largest proportion of the variance, whereas body
weight had little influence or was eliminated from the model. The slopes of the
regression lines of bone mineral content or density on body weight were
significantly steeper in the subgroup of gymnasts (P < 0.001), whereas the slopes
of the regression lines of bone mineral content or density on lean tissue mass
were significantly less steep in the swimmers (P < 0.05). CONCLUSION: Our data
indicate that lean tissue mass is a significant predictor of bone mass in
prepubertal girls and explains a larger part of the variance of bone mineral
content and density than body weight. Use of body weight as a covariate in
studies of bone mineral density may lead to erroneous results in prepubertal
girls.
PMID- 9636953
TI - Update on lumbar spinal stenosis. Retrospective study of 62 patients and review
of the literature.
AB - PURPOSE AND METHODS: Although lumbar spinal stenosis syndrome is extremely
common, considerable controversy continues to surround its classification,
diagnosis, and treatment. We retrospectively reviewed the medical charts of 62
patients admitted for lumbar spinal stenosis syndrome, and we compared our
findings to those in the literature. There were 31 women and 31 men. Mean age was
71.8 years. The most common symptoms were positional radiculopathy (92%) and low
back pain (95%). The more suggestive sign of pseudoclaudication was observed in
only 75% of cases, in keeping with earlier studies. Neurologic symptoms
consisting primarily in mild motor loss were present in 15 patients. RESULTS: The
most common physical finding was pain during spinal extension (70%). Adopting a
bent forward position during walking, a very suggestive manifestation, was seen
in 15 patients. Imaging study findings included extensive changes in the discs
and facet joints, disc protrusion, scoliosis, and degenerative spondylolisthesis.
Myelography was rarely needed. There are no criteria sets for lumbar spinal
stenosis syndrome. The diagnosis rests on clinical grounds, and extensive imaging
studies are usually unnecessary. Our patients were treated with repeated
corticosteroid injections into the thecal sac or epidural space and/or into the
facet joints. Only eight patients required surgery. CONCLUSION: Our study
supports the view that most cases of lumbar spinal stenosis can be managed
conservatively.
PMID- 9636954
TI - Dysphagia, headache, and dizziness as symptoms of cervical spine disorders.
PMID- 9636955
TI - Abducens palsy after an intrathecal glucocorticoid injection. Evidence for a role
of intracranial hypotension.
AB - We report a case of abducens palsy eight days after an intrathecal glucocorticoid
injection followed by post-lumbar puncture syndrome. T1-weighted magnetic
resonance imaging scans showed marked diffuse postgadolinium enhancement of the
supra- and infratentorial meninges consistent with intracranial hypotension
syndrome. The palsy resolved almost completely and a repeat magnetic resonance
imaging scan done after four months was normal. The mechanism of the meningeal
thickening and contrast enhancement is discussed.
PMID- 9636956
TI - Optic neuropathy in a child with primary Sjogren's syndrome.
AB - An eight-year-old girl developed optic neuritis followed by primary Sjogren's
syndrome confirmed by a lip biopsy. Glucocorticoid therapy combined during six
months with monthly intravenous pulse cyclophosphamide ensured resolution of the
sicca syndrome but failed to improve the visual impairment. This is the second
pediatric case of optic neuritis associated with primary Sjogren's syndrome, and
the first pediatric case in which optic neuritis was the only neurologic
manifestation.
PMID- 9636957
TI - Brachial plexopathy and Horner's syndrome as the first manifestations of internal
jugular vein thrombosis inaugurating polycythemia vera.
PMID- 9636958
TI - Amyloidosis of the urinary bladder: a rare cause of total hematuria in rheumatoid
arthritis.
PMID- 9636959
TI - Spondylarthropathy in patients with the HIV.
PMID- 9636960
TI - Osteosarcoma of the sacrum complicating Paget's disease of bone.
PMID- 9636961
TI - Myocardial perfusion after coronary artery bypass surgery. A study using
ectomographic myocardial scintigraphy and adenosine provocation.
AB - A study was conducted to determine the time dependency of myocardial perfusion
improvement after coronary artery bypass graft (CABG) surgery. Seventeen 3-vessel
diseased patients (16 male, 1 female) scheduled for CABG surgery from a cardiac
surgical and intensive-care unit were examined. Ten of the 17 patients returned
for examination after 1 year. A titrated adenosine infusion was used to expose
reversible ischemia. Tc99m-sestamibi was injected at rest and at maximum
adenosine infusion rate, and isotope distribution was determined using
ectomographic myocardial scintigraphy. Visually scored percent isotope uptake
defect size and percent uptake reduction were assessed. It was found that resting
isotope uptake defects were unchanged 1 h after surgery, increased in severity
after 1 week, and after 1 year were 24% less than the preoperative scores (p <
0.01) and 55% less than after 1 week (p < 0.001). It was found that adenosine
infusion induced a 57% increase in average defect score preoperatively (p <
0.001) but no increase postoperatively. No differences were seen between regions
supplied by arterial or venous grafts. Isotope uptake defects increased between 1
h and 1 week after CABG surgery, and after 1 year the scores were less than those
recorded preoperatively and after 1 week. Adenosine-induced reversible isotope
uptake changes seen preoperatively were eliminated postoperatively in all vessel
regions.
PMID- 9636962
TI - Autologous blood patch pleurodesis in spontaneous pneumothorax with persistent
air leak.
AB - In a prospective study series of 167 patients with tube thoracostomy for
spontaneous pneumothorax in 1993-1996, 32 patients (age range 16-79 years, mean
age 45.5 years) were treated with autologous blood-patch pleurodesis for
persistent air leak. In 27 (84%) of cases the air leak ceased within 72 h after
the pleurodesis. The duration of air leak was significantly shorter (p < 0.01)
than in simple drainage. Empyema developed in three cases, and two patients with
failed pleurodesis required open thoracotomy. Minor complications, mainly fever
and pleural effusion, occurred in nine patients. Neither analgesia nor sedation
was required during or after pleurodesis. There was no recurrence of pneumothorax
during 12-48 months of observation, whereas simple drainage was followed by
recurrence in 22 patients. Blood-patch pleurodesis is a simple, effective and
painless method in pneumothorax, but carries an increased risk of intrathoracic
infection.
PMID- 9636963
TI - The Barath Cutting Balloon versus conventional angioplasty. A randomized study
comparing acute success rate and frequency of late restenosis.
AB - In a randomized multicenter study initial success rate and 6 months' follow-up
were compared between coronary angioplasty performed with the Barath Cutting
Balloon (group A, n = 32) and conventional balloons (group B, n = 32) in patients
with type A or B lesions in native coronary arteries. The culprit lesion was not
reached in one patient in group A. Initial success rates were similar with and
without additional stenting (8 in group A and 10 in group B). Angiographic follow
up data (in 95%) revealed a non-significant improvement in minimal lumen
diameter, diameter stenosis in group A. Restenosis developed in 16.7% of group A
vs 25.8% of group B, (p = 0.57). A separate analysis of stented patients showed
no restenosis in group A and restenosis in 4 out of 10 patients in group B (p =
0.10). A possible beneficial effect of the Cutting Balloon with respect to in
stent restenosis requires further studies.
PMID- 9636964
TI - Activated and total coagulation factor VII, and fibrinogen in coronary artery
disease.
AB - Fibrinogen (FBG) and total coagulation factor VII (FVIIc) concentrations are
higher in those patients with coronary artery disease who are at increased future
risk of acute ischemic events. The relationship between activated factor VII
(FVIIa) and cardiovascular events, however, has not been intensively studied.
Data were collected from 401 consecutive patients who underwent coronary
angiography because of suspected coronary artery disease. Conventional risk
factors FVIIc, FVIIa and FBG were assessed in relation to the severity of
coronary artery disease, left ventricular ejection fraction, and previous
clinical events. A strong positive correlation was found between FVIIa and FVIIc
(p < 0.001), but neither FVIIa nor FVIIc correlated with FBG. No correlation was
found between FVIIa, FVIIc or FBG levels and stenosis score for the severity of
coronary artery disease, and all were similar in patients with stable or unstable
angina pectoris. Multivariate regression analysis showed FVIIc to be higher in
women (p = 0.004), and positively related to triglycerides (p = 0.001) and HDL
cholesterol (p = 0.006), but not to a previous myocardial infarction or total
cholesterol. FVIIa, on the other hand, was lower in patients with a previous
myocardial infarction (p = 0.004), higher in women (p = 0.001) and those that
previously had undergone percutaneous transluminal coronary angioplasty (p =
0.039), and positively related to total cholesterol (p = 0.011), duration of
coronary artery disease (p = 0.032), and smoking (p = 0.008). FBG was positively
associated with a previous myocardial infarction (p = 0.013), hypertension (p =
0.016), smoking (p = 0.005), and the thrombocyte count (p < 0.001). Finally,
stepwise logistic regression analysis verified a previous myocardial infarction
to be negatively associated with FVIIa (p = 0.03), and positively with FBG (p =
0.03), total cholesterol (p = 0.02), and the severity of coronary artery disease
(p < 0.001). In conclusion, in patients suspected of coronary artery disease
undergoing cardiac catheterization, FVIIa was decreased and FBG increased in
those who had a previous myocardial infarction. FVIIa, FVIIc, or FBG levels were
not, however, related to the severity of coronary artery disease, and they were
similar in patients with stable or unstable angina pectoris.
PMID- 9636965
TI - Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome
after lung transplantation.
AB - Bronchiolitis obliterans syndrome (BOS) develops in one-third of lung transplant
recipients. A fibroproliferative process involving mesenchymal cells is observed
histopathologically. In order further to evaluate the pathomechanisms of BOS, the
gene expression of platelet-derived growth factor (PDGF)-B and transforming
growth factor (TGF)-beta 1 in bronchoalveolar lavage (BAL) cells of six lung
transplant recipients and appropriate controls was studied. Equal amounts of
total RNA were submitted to semiquantitative reverse transcription/polymerase
chain reaction (RT-PCR), amplifying actin, PDGF-B and TGF-beta 1 using
established protocols and primer sets. The signal/actin ratio was calculated
based on laser densitometry measurements. TGF-beta 1 transcripts were detected in
all samples, and a slight increase in BOS patients was observed. PDGF-B mRNA was
increased in BAL samples from BOS patients compared to unaffected recipients and
controls. Plotting the FEV1 in percent of vital capacity and the PDGF expression
in BOS patients revealed an increased PDGF signal preceding lung function
deterioration. The data were consistent with the hypothesis based mainly on in
vitro findings that PDGF and TGF-beta contribute to the development of BOS.
PMID- 9636966
TI - Thymic lymphoepithelioma-like carcinoma associated with thymoma in a patient with
ocular myasthenia.
AB - A 65-year-old woman with ocular myasthenia was found to have three tumours in the
anterior mediastinum, revealed by magnetic resonance imaging. All three lesions
were radically resected. Histologically, one was a mixed-type thymoma, one a
thymic lymphoepithelioma-like carcinoma, and the third had features of both these
types. This appears to be the first reported case of coexisting thymic
lymphoepithelioma-like carcinoma (TLC) and thymoma associated with ocular
myasthenia.
PMID- 9636967
TI - Resection of distal tracheal and carinal tumours with the aid of cardiopulmonary
bypass.
AB - Two cases of carinal and tracheal reconstruction with the aid of cardiopulmonary
bypass (CPB) are presented. The technical problems of surgery and anaesthesia
which necessitated CPB in these two patients are discussed. CPB provides both
adequate oxygenation and an unobstructed surgical field with optimal access to
the trachea and carina. It permits atraumatic handling of the airways and
reduction of anastomotic tension during the repair.
PMID- 9636968
TI - Bochdalek hernia in an adult.
AB - Congenital diaphragmatic Bochdalek hernia is rarely seen in adults. It may
present with jejunal perforation and strangulation. In a 28-year-old man
presenting with nausea and vomiting, absence of respiratory murmur at
auscultation, loops of small intestine with air-fluid levels were
radiographically visualized in the left hemithorax. Surgery revealed 1.5-m of
herniated jejunum with three perforations and necrotic areas, 40 cm of which was
resected. The patient remains well ten years postoperatively.
PMID- 9636969
TI - Assessment of left ventricular dysfunction and remodeling by determination of
atrioventricular plane displacement and simplified echocardiography.
AB - Heart failure is a common disease characterised by poor prognosis and frequent
hospitalisations, constituting a major economic burden to society. Mortality and
morbidity can be reduced by optimal treatment, requiring objective evaluation of
cardiac function and anatomy. The development of symptomatic HF can be prevented
by initiating adequate treatment in early stages when LVD is still asymptomatic.
Asymptomatic patients can be identified only by screening for LVD among patients
at risk of developing HF, such as those with IHD, HT, and diabetes. However,
there is a severe lack of resources to assess cardiac function and anatomy in all
patients at risk. Consequently, many patients with latent HF will remain
undetected, and in patients with symptomatic HF treatment will not be optimal.
Simplified echocardiography, a 5-minute echocardiogram based on visual estimation
of cardiac function and anatomy, is an inexpensive and accurate method for
diagnosis and screening for latent and symptomatic HF. The long axis shortening
of the LV is related to LV function and can be measured by AVPD. Determination of
left AVPD is a reliable, reproducible, readily mastered, quickly performed and,
therefore, inexpensive method that can be used in almost all patients for
evaluation of LV function, as well as for prognostication in HF. Left AVPD
reflects both systolic and diastolic LV function. Simplified echocardiography is
useful for screening of asymptomatic patients at risk of developing HF, and for
routine diagnostic purposes in patients with symptoms suggestive of HF. In
patients with LVSD, simplified echocardiography may be combined with a
determination of left AVPD for prognostication and for optimal detection of
changes in LV function over time.
PMID- 9636970
TI - The role of steroids and their effects on phospholipase A2. An animal model of
radiculopathy.
AB - STUDY DESIGN: The possible role of phospholipase A2 in an animal model for lumbar
radiculopathy and mechanisms of epidural steroid injections were studied.
OBJECTIVES: To clarify the pathophysiologic mechanism of the recently proved
animal model for lumbar radiculopathy and to characterize further the mechanisms
of action of steroids. SUMMARY OF BACKGROUND DATA: There have been several
reported animal models of peripheral neuropathy. Recently an animal model that
shows reliable behavioral and neurochemical changes was proposed, and epidural
steroid injections in this model were effective in the reduction of thermal
hyperalgesia and allodynia. METHOD: In a behavioral study, 24 rats were divided
into 4 groups: Group I, loose ligature of the left L4 and L5 nerve roots with 4-0
chromic gut sutures and an epidural injection of 0.1 mL of saline at 3 days after
surgery; Group II, same as Group I but with an epidural injection of 0.1 mL of
betamethasone on the day before the operation; Group II, same as Group II except
injection at 1 day after surgery; Group IV, same as Group II except injection at
3 days after surgery. To test the phospholipase A2 activity in the nerve roots
and dorsal root ganglia after the operation, eight rats were killed at given
intervals. Analysis of variance techniques were used to test behavioral pattern
changes and phospholipase A2 activity across time in each group. RESULTS: Thermal
hyperalgesia reached its maximal point at 3 weeks after surgery in Group I, but
in steroid injection groups, the recovery from hyperalgesia was faster than in
Group I. However, there was no significant difference in recovery time among
steroid injection groups. The level of phospholipase A2 activity was at its
maximum at 1 week after surgery in Groups I and IV. It showed a steady reduction
in the steroid group, whereas it remained relatively high and dropped rapidly
after 3 weeks in the saline-treated group, and returned to the level of a normal
nerve root at 6 weeks after surgery. CONCLUSION: These results suggest that the
behavioral pattern changes observed in the irritated nerve root model are caused
in part by a high level of phospholipase A2 activity initiated by inflammation,
and that the mechanism of action of epidural steroid injection in this model is
inhibition of phospholipase A2 activity.
PMID- 9636971
TI - Is there a clinical correlate to the histologic evidence of inflammation in
herniated lumbar disc tissue?
AB - STUDY DESIGN: The presence of inflammatory cells was examined
immunohistochemically in routinely processed resection specimens of the lumbar
disc. The histologic results were compared with prospectively obtained clinical
data. OBJECTIVES: To assess the clinical relevance of inflammatory cells in
herniated lumbar disc specimens. SUMMARY OF BACKGROUND DATA: It is postulated
that in addition to nerve root compression, an inflammatory stimulus of the
herniated lumbar disc is responsible for sciatic pain and radiculopathy. However,
the clinical relevance of the histologically described inflammatory infiltrates
is not defined clearly. METHODS: Disc specimens from 44 patients who underwent
surgery for lumbar disc herniation were studied immunohistologically. Before
surgery, severity of pain was classified in each patient according to a visual
analog scale, and general clinical data were recorded prospectively. RESULTS:
Varying amounts of inflammatory cells could be demonstrated in the resected disc
tissue. In the statistical analysis, no statistically significant correlation
between the histologic evidence of macrophage infiltrates and the pain grading
scale or the clinical data was noted. CONCLUSIONS: There is no statistically
significant correlation between macrophage infiltrates in herniated lumbar disc
specimens and the obtained clinical data.
PMID- 9636972
TI - Patients with low back pain not returning to work. A 12-month follow-up study.
AB - STUDY DESIGN: A prospective study of patients treated with a light mobilization
program for long-term low back pain. OBJECTIVES: To examine whether medical,
psychological, or social factors predict failure to return to work within 12
months in the Scandinavian system of compulsory workers' compensation and social
insurance, after a light mobilization program administered 8-12 weeks after
initial sick leave. SUMMARY OF BACKGROUND DATA: The relative power of predicting
factors varies in previous work, and there are no previous data on prognostic
factors for light mobilization programs. METHOD: Patients (n = 260) on sick leave
for 8-12 weeks for low back pain were examined with a battery of psychological
and medical tests, before entering a light mobilization program. The treatment
was given regardless of radiographic or clinical findings. The patients were
encouraged to be active participants in the management and prevention of their
back pain. Their sick leave status then was checked through registers 12 months
after they had entered the treatment program. RESULTS: For those not returning to
work within 12 months (23%), only combined models had acceptable predictive power
(77%; discriminant analyses). Dominant variables were low Internal Health Locus
of Control Score, restricted lateral mobility, and reduced work ability. The
predictive value of each set of variables, taken alone, was significant only for
medical variables (67% correct prediction). CONCLUSIONS: The final discriminant
function may have potential as a brief screening instrument for the number of
patients with low back pain who do not benefit from the light mobilization
program.
PMID- 9636973
TI - A human cadaver model for determination of pathologic fracture threshold
resulting from tumorous destruction of the vertebral body.
AB - STUDY DESIGN: Thoracic vertebrae were subjected to compressive loads after
drilling of the centrum to simulate destruction from metastatic tumorous
involvement. OBJECTIVE: To determine whether a threshold exists that is
predictive of fractures to establish a correlation between significant variables
and vertebral strength. SUMMARY OF BACKGROUND DATA: The mechanical effects of
metastatic destruction of thoracic vertebral bodies and their correlation to
pathologic fractures has been analyzed in few studies. In additional studies on
intact vertebral strength, investigators have determined that bone mineral
density and geometric factors are important. METHOD: Fifty-four cadaveric
thoracic vertebrae were studied. All were examined by quantitative computed
tomography. T4 and T10 served as mechanical controls to predict the intact
strength of T7. The test vertebrae were drilled from the anterior cortex through
to the posterior cortex before they were loaded. RESULTS: Linear correlation
between the strength of T4 and T10 in each spine supported the predicted
strengths of T7. Because of variation from other factors, no threshold defect
size was noted beyond which failure consistently occurred. Results of linear
correlation analyses showed that the best combination of parameters for
predicting vertebral strength was the product of bone mineral density and the
remaining intact vertebral body cross-sectional area. This vertebral strength
index correlated linearly with the strength of intact and compromised T7
vertebrae (r2 = 0.52). CONCLUSIONS: The vertebral strength index can be used to
predict the strength of any thoracic vertebra. When compared with an idealized
vertebral strength index based on the intact vertebral cross-sectional area and
normal bone mineral density, a patient's actual vertebral strength index can be
used as one of the criteria for prophylactic stabilization.
PMID- 9636974
TI - Changes in cadaveric cancellous vertebral bone strength in relation to time. A
biomechanical investigation.
AB - STUDY DESIGN: A biomechanical study was conducted during a 3.5-day period to test
for changes occurring in pullout strengths of cancellous screws inserted into
human cadaveric vertebral bodies. OBJECTIVES: To quantify, within the testing
time of 3.5 days, the possible changes to the mechanical properties of cadaveric
vertebral bodies, resulting from structural degradation caused by postmortem,
time-dependent, autolytic processes during mechanical testing of implant-bone
biomechanics. SUMMARY OF BACKGROUND DATA: Biomechanical testing of whole spinal
implants and analysis of the screw-bone interface of spinal implants is an area
of clinical interest that frequently requires the use of cadaveric spine
specimens. Changes in vertebral bone properties during the testing period may
invalidate experimental results, but no data are available on degradation of bone
during the testing period. METHODS: Anterior oblique cancellous screws were
inserted into human vertebral bodies from which the ventral cortex had been
removed. The pullout strength was measured at 0, 24, 60, and 84 hours after
insertion. The tests were performed on 48 human vertebral bodies, which were
stored by freezing to -23 C, thawed for testing, and kept at room temperature
during the testing time for as long as 84 hours. RESULTS: The axial pullout
strength showed no statistically significant change during 84 hours (P = 0.15).
There were no significant differences attributable to vertebral level from T4 to
L4, probably because the ventral cortices had been removed (P = 0.7).
CONCLUSIONS: During 3.5 days, there were no changes in pullout strength of
vertebral cancellous bone. In biomechanical studies during a maximum period of 3
days with a small number of cadaveric spines (e.g., four spine specimen) the time
dependent changes in pullout strength play a less significant role than do the
interspine differences. Interspine differences should be regarded as an important
factor to be considered in the design of biomechanical tests.
PMID- 9636975
TI - Moments and forces during pedicle screw insertion. In vitro and in vivo
measurements.
AB - STUDY DESIGN: Moments and forces during pedicle screw insertion were measured in
vivo and in vitro and were correlated to several parameters of the screw-bone
interface. OBJECTIVES: To compare the in vitro and in vivo screw insertion loads
and to relate these measurements to bone mineral density, pedicle size, and other
screw parameters (material, diameter). SUMMARY OF BACKGROUND DATA: The in vitro
screw insertion torque has been correlated to the screw pullout forces and the
number of cycles to ultimate interface failure. However, there are no comparable
in vivo data. METHODS: One hundred three pedicle screws were included in the
study, 43 in vivo and 60 in vitro. Duel-energy x-ray absorptiometry boen mineral
density data were available for 20 in vivo and 32 in vitro specimens. A custom
made sterilizable six-axis load cell was integrated into a torque wrench,
enabling the recording of the applied moments and forces during screw insertion.
Statistical analysis was performed to detect differences and correlations.
RESULTS: The mean in vivo insertion torque (1.29 Nm) was significantly greater
than the in vitro value (0.67 Nm). The linear correlation between insertion
torque and bone mineral density was significant for the in vitro data but not for
the in vivo data. No correlation was observed between insertion torque and
pedicle diameter. Two patterns of torque were observed during the insertion
process. CONCLUSIONS: There is a significant difference between the insertion
loads measured in vivo and those measured in vitro. Additional research is needed
to verify whether this method provides an indication of screw fixation quality.
PMID- 9636976
TI - Anatomic considerations of anterior transarticular screw fixation for
atlantoaxial instability.
AB - STUDY DESIGN: Anatomic parameters of C1 and C2 were measured in 30 dried human
cervical spines. Anterior transarticular C1-C2 screws were placed in 15 cadaveric
spines. OBJECTIVE: To provide anatomic data for anterior transarticular
atlantoaxial screw or C1-C2 screw and plate fixation. SUMMARY OF BACKGROUND DATA:
A posterior approach to fixation in the atlantoaxial joint has been well
described. Damage to the vertebral artery is documented as a rare complication of
posterior atlantoaxial transarticular screw fixation. An anterior surgical
approach to exposing the upper cervical spine for internal fixation and bone
graft recently has been developed. No anatomic information regarding the anterior
transarticular atlantoaxial screw or screw and plate fixation between C1 and C2
is available in the literature. METHODS: Direct measurements using digital
calipers and a goniometer were taken from 30 pairs of dried human C1 and C2
vertebrae. The anterior transarticular C1-C2 screw insertion point is at the
junction of the lateral edge of the C2 vertebral body to 4 mm above the inferior
edge of the C2 anterior arch. The parameters related to anterior transarticular
atlantoaxial screw fixation or screw and plate fixation between the C1 lateral
mass and the C2 vertebral body were measured. Fifteen embalmed cadavers were used
for anterior C1-C2 transarticular screw placement. Longer screws (30-40 mm) were
used to detect whether the screw tips violated the upper cervical canal or
vertebral arteries. RESULTS: In the anterior transarticular atlantoaxial screw
placement, lateral angulation of the screw placement relative to sagittal plane
ranged from 4.8 +/- 1.8 degrees to 25.3 +/- 2.6 degrees. The posterior angulation
of the screw placement relative to the coronal plane ranged from 12.8 +/- 3.1
degrees to 22.6 +/- 3.2 degrees. The length of the medial screw path ranged from
14.7 +/- 1.5 mm to 25.4 +/- 2.8 mm. In the anterior screw and plate fixation, the
anteroposterior diameter of the inferior facet articular surface ranged from 16.2
+/- 1.6 mm to 17.1 +/- 1.8 mm. The anteroposterior diameter of the C2 vertebral
body ranged from 9.3 +/- 1 mm to 16.2 +/- 1.8 mm. The anterior prevascular
retropharyngeal approach appropriately exposed the atlantoaxial joint for
anterior transarticular C1-C2 screw placement. No screws violated the vertebral
artery and cervical canal. CONCLUSIONS: An anterior transarticular atlantoaxial
screw 15-25 mm long can be inserted with a lateral angulation of 5-25 degrees
relative to the sagittal plane and a posterior angulation of 10-25 degrees
relative to the coronal plane. Additionally, in C1-C2 anterior plate fixation
screws 15 mm long could be anchored in the inferior facet of the C1, and screws 9
15 mm long could be anchored in the C2 vertebral body.
PMID- 9636977
TI - Functional turbo spin echo magnetic resonance imaging versus tomography for
evaluating cervical spine involvement in rheumatoid arthritis.
AB - STUDY DESIGN: Comparison of findings in plain radiography and conventional
tomography with findings in plain radiography and magnetic resonance imaging of
the upper cervical spine in consecutive patients with rheumatoid arthritis and
with known or suspected abnormalities of the cervical spine. OBJECTIVES: To
determine whether plain radiography and magnetic resonance imaging provide enough
information to dispense with tomography in investigations of cervical spine
involvement in rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: With the recent
advances in magnetic resonance imaging technology and the proliferation of
magnetic resonance imaging techniques for specific clinical conditions. METHODS:
Twenty-eight patients with rheumatoid arthritis and with known or suspected
abnormalities of the cervical spine underwent a clinical neurologic examination;
plain radiography, including full flexion lateral radiography; anteroposterior
and lateral tomography at C1-C2; and magnetic resonance imaging at the same level
in neutral position and in flexion. Two radiologists evaluated one image set
consisting of plain radiography and conventional tomographic images and another
image set consisting of plain radiography and magnetic resonance images, for each
patient. RESULTS: Compared with conventional tomography and plain radiography,
magnetic resonance imaging and plain radiography showed cystic lesions and
erosions of the odontoid process and vertical atlantoaxial subluxation more
often, showed anterior subluxation as often, and showed lateral atlantoaxial
subluxation less often. CONCLUSION: Magnetic resonance imaging produces
sufficiently distinct images of destruction of the odontoid and subluxations for
it to replace conventional tomography in investigations of upper cervical spine
involvement in rheumatoid arthritis.
PMID- 9636978
TI - The radiographic and imaging characteristics of porous tantalum implants within
the human cervical spine.
AB - STUDY DESIGN: Seven cadaveric cervical spines were implanted with a porous
tantalum spacer and a titanium alloy spacer, and their radiographic and imaging
characteristics were evaluated. OBJECTIVE: To determine the radiographic
characteristics of porous tantalum and titanium implants used as spacers in the
cervical spine. SUMMARY OF BACKGROUND DATA: Anterior decompressive surgery of the
disc space or the vertebral body creates a defect that frequently is repaired
with autologous bone grafts to promote spinal fusion. Donor site morbidity,
insufficient donor material, and additional surgical time have spurred the
development of biomaterials to replace or supplement existing spinal
reconstruction techniques. Although the promotion of a solid bony fusion is
critical, the implanted biomaterial should be compatible with modern imaging
techniques, should allow visualization of the spinal canal and neural foramina,
and should permit radiographic assessment of bony ingrowth. METHODS: Cadaveric
spines containing the implants were imaged with plain radiography, computerized
tomography, and magnetic resonance imaging. The image distortion produced by the
implants was determined qualitatively and quantitatively. RESULTS: The tantalum
and titanium spacers were opaque on plain radiographic films. On computed
tomographic scans, more streak artifact was associated with the tantalum implants
than with the titanium. On magnetic resonance imaging, the porous tantalum
implant demonstrated less artifact than did the titanium spacer on T1- and T2
weighted spin echo and on T2*-weighted gradient-echo magnetic resonance images.
Overall, the tantalum implant produced less artifact on magnetic resonance
imaging than did the titanium spacer and therefore allowed for better
visualization of the surrounding bony and neural structures. CONCLUSION: The
material properties of titanium and porous tantalum cervical interbody implants
contribute to their differential appearance in different imaging methods. The
titanium implant appears to image best with computed tomography, whereas the
porous tantalum implant produces less artifact than does the titanium implant on
several magnetic resonance imaging sequences.
PMID- 9636979
TI - Predictive signs of discogenic lumbar pain on magnetic resonance imaging with
discography correlation.
AB - STUDY DESIGN: The correlation between discogenic lumbar pain and disc morphology
was investigated by using magnetic resonance imaging and discography. OBJECTIVES:
To assess the various pathologic parameters seen on magnetic resonance imaging in
patients with discogenic lumbar pain and to correlate them with observations on
discography. SUMMARY OF BACKGROUND DATA: Although numerous previous studies on
the subject have been performed, the correlations between various pathologic
findings on magnetic resonance imaging and pain reproduction by provoked
discography have not been explained fully. METHODS: One hundred and one lumbar
discs in 39 patients were studied with magnetic resonance imaging and pain
provocation discography. When pain reproduction under discography was concordant,
various pathologic parameters on magnetic resonance imaging were analyzed by
three statistical parameters to determine the associated magnetic resonance
imaging findings. RESULTS: Radial tears commonly are demonstrated on magnetic
resonance imaging in discs with concordant pain on discography. The presence of
these tears is not a reliable predictor of a painful disc on discography.
Although a high-intensity zone on T2-weighted images is a relatively reliable
predictor of pain, the statistical values were lower than those in previous
studies. Massive degeneration and severe disc height loss were rare in this
population. These findings were good predictors of pain on disc injection.
CONCLUSIONS: Although the lumbar intervertebral discs with posterior combined
anular tears are likely to produce pain, the validity of these signs for
predicting discogenic lumbar pain is limited.
PMID- 9636980
TI - Risk of blood contamination of health care workers in spine surgery. A study of
324 cases.
AB - STUDY DESIGN: The relative risk of blood contamination during spine surgery was
studied using data collected from 324 procedures. OBJECTIVES: To analyze
demographic factors that predict blood-borne pathogens in the population of spine
surgery patients, study the rates and patterns of blood contamination in health
care workers (i.e., skin-penetrating incidents and nonpenetrating surface skin
contamination from patients' blood) and compare those risks with those in other
surgical departments, and analyze the effectiveness of barrier systems worn by
the surgical team. SUMMARY OF BACKGROUND DATA: The Centers for Disease Control
and Prevention has reported 49 health care workers infected by the human
immunodeficiency virus through occupational exposure. Several studies have noted
the risk of blood contamination in various surgical departments, but the relative
risk during spine surgery has not been determined. METHODS: This year-long survey
included 9795 cases, or 60,789 health care worker--patient contacts, of which
spine disorders comprised 324 cases (2234 health care workers and patients). Data
collection forms were designed and inservice training conducted with operating
room staffs. Information regarding type of case, staff position (surgeon,
assistant, scrub nurse, circulator), protective clothing worn, length of
operating room time, blood loss, incidence of blood spills, was recorded, among
other data. RESULTS: Prevalence of human immunodeficiency virus in patients in
the overall series was 0.19% versus 0.93% in spine patients. The rate of HCW
contamination in the overall series was 7.76%, of which 0.92% resulted from skin
penetrating incidents. Contamination in spine surgery occurred in 31.86% of
cases, of which 1.23% were the result of skin-penetrating incidents. CONCLUSIONS:
Health care workers in spine surgery have a statistically significant overall
higher risk of blood contamination than do those in other surgical departments.
The increased risk occurred with blood contacting intact skin. There was no
higher risk for skin penetrating injury. Analysis of data suggests that health
care workers always should wear double gloves, forearm-reinforced gowns, and eye
protection.
PMID- 9636981
TI - The Bagby and Kuslich method of lumbar interbody fusion. History, techniques, and
2-year follow-up results of a United States prospective, multicenter trial.
AB - STUDY DESIGN: A prospective, multicenter trial of the Bagby and Kuslich method of
lumbar interbody stabilization for chronic discogenic low back pain, with follow
up evaluation at 3 months, 6 months, and yearly thereafter, with independent
radiographic analysis. OBJECTIVES: To report the history of development, the
surgical techniques, and results of the Bagby and Kuslich method when used to
manage discogenic pain of the lumbar spine in humans. SUMMARY OF BACKGROUND DATA:
Disabling chronic low back pain frequently is resistant to conservative
management. The "Bagby Basket" effectively has fused the equine and baboon spine.
The results of biomechanical and animal studies performed over the last 20 years
have suggested that a similar but improved design--the Bagby and Kuslich device-
would be useful in stabilizing the human spine. METHODS: From 1992 to 1995, 947
patients with chronic discogenic low back pain were treated by Bagby and Kuslich
interbody fusion in a strict, multicenter, prospective clinical trial by using
either the open anterior or open posterior approach. The study involved 42
surgeons at 19 medical centers. The authors of the current report analyzed the
fusion rates, pain relief, functional status, and complications occurring in
patients who underwent long-term follow-up observation. RESULTS: The Bagby and
Kuslich method is safe and effective when compared with methods described in
previous reports of posterior and anterior lumbar interbody arthrodesis performed
by using bone graft alone. Fusion occurred in 91% of patients at 24 months after
surgery, and pain was eliminated or reduced in 84%. Function was improved in 91%.
There were no device-related deaths, cases of major paralyses, device failures,
or deep infections. CONCLUSIONS: Carefully selected middle-aged patients with
chronic low back pain secondary to degenerative disc disease can be treated
effectively and safely by skilled surgeons using the Bagby and Kuslich device for
one- and two-level interbody fusion.
PMID- 9636982
TI - Atlantoaxial instability complicating radiation therapy for recurrent
nasopharyngeal carcinoma. A case report.
AB - STUDY DESIGN: A case report of a patient in whom atlantoaxial instability
developed secondary to repeat radiation therapy for recurrent nasopharyngeal
carcinoma. OBJECTIVES: To illustrate a dramatic and previously unreported
complication of local radiation to the posterior nasopharynx. SUMMARY OF
BACKGROUND DATA: Nasopharyngeal carcinoma is an unusual tumor that usually is
managed with local, external-beam radiation. It is not thought to involve the
cervical spine directly, although local invasion of the skull base is common.
METHODS: A review of the medical records and radiographs of the only patient
known to develop this complication of radiation used to manage nasopharyngeal
carcinoma. RESULTS: Atlantoaxial instability developed in a patient as a result
of repeat radiation for a locally recurrent tumor. The instability was associated
with intrusion of the anterior arch of C1 into the posterior nasopharynx and was
managed successfully with a posterior stabilization using transarticular screws
and supplemental wiring. CONCLUSIONS: Patients who have undergone local
irradiation for nasopharyngeal carcinoma may be at risk for developing
atlantoaxial instability.
PMID- 9636983
TI - Traumatic pneumomyelography. A marker of spinal column injury in the face of
innocuous spine fractures: two case reports.
AB - STUDY DESIGN: A report of two cases of spinal column injury. OBJECT: To document
the presence of air within the spinal canal following spinal fractures. SUMMARY
OF BACKGROUND DATA: Only two previous cases of air in the spinal canal have been
reported in the English literature. This report emphasizes that even with
innocuous-appearing fractures of the thoracic spine, a similar phenomenon can
occur. METHODS: The author reports on the medical records and radiographic
investigations related to these two cases. RESULTS: Air within the cervical,
thoracic, and lumbar spine was identified in what appeared to be minor spinal
fractures of the thoracic spine. CONCLUSIONS: In cases of relatively undisplaced
fractures of the thoracic spine associated with air in the spinal canal, one
should be alert to the possibility of more unstable injuries that may have
undergone significant displacement at the time of the fracture.
PMID- 9636984
TI - Conservative treatment of acute and chronic nonspecific low back pain.
PMID- 9636985
TI - [Sick building syndrome and HVAC system: MVOC from air filters].
AB - Growth and emissions of volatile metabolites of microorganisms on air filters are
suspected to contribute to health complaints in ventilated rooms. To prove the
microbiological production of volatile organic compounds (MVOC), concentrations
of aldehydes and ketones were determined in two large HVAC systems. The in situ
derivated aldehydes and ketones (as 2,4-dinitrophenyl-hydrazones) were analysed
by HPLC and UV detection. The detection limit of each compound was 1 ppb (margin
of error < 10%). Field measurements were carried out before and after the
prefilters and the main filters, respectively, to investigate whether aldehydes
and ketones increase in concentration after filters of HVAC systems. First
results show that the compounds formaldehyde, acetaldehyde and acetone could be
detected before and after the filters. The concentrations of these VOC after the
filters were significantly increased--as a mean over twenty measurements--,
especially as far as filters made of glass fibre are concerned. However the found
concentrations were low and mostly comparable to outdoor findings. In
simultaneous laboratory experiments pieces of used filter material of one HVAC
system and unused filter pieces (for blank values) were examined in small
incubation chambers to investigate the possible production of MVOC. For the
incubation a temperature of 20 degrees C and a relative humidity of 95% was
chosen. In these experiments an almost identical spectrum of compounds
(formaldehyde and acetone) was found as in the field measurements. The
concentrations of these compounds were higher in the chambers with the used
filter pieces. The concentration of acetone ranged up to almost 12 mg/m3.--As our
field experiments correspond with our laboratory experiments, we assume that the
microbial production of volatile organic compounds in HVAC systems under
operating conditions is possible.
PMID- 9636986
TI - Occurrence of gram-negative bacteria in drinking water undergoing softening
treatment.
AB - A study was carried out on the presence of Gram-negative bacteria in the
municipal waters of Bologna (Italy) undergoing softening using domestic ion
exchangers with an automatic disinfection mechanism. The softening process was
seen to cause a 15 fold increase in 22 degrees C and 36 degrees C heterotrophic
plate counts. There was a 30 fold increase in Gram-negative bacteria and their
number correlated directly with temperature and inversely with active residual
chlorine. Organic matter had no effect on bacterial growth. The most commonly
found bacteria were various species of Pseudomonas (87.6%) (Ps. acidovorans, Ps.
denitrificans, Ps. fluorescens and Ps. testosteroni) followed by Aeromonas
hydrophila (5.6%) and Stenotrophomonas (Xantomonas) maltophilia (3.8% in outgoing
water). Pseudomonas aeruginosa (present in 5.6% of incoming water samples and
0.4% of outgoing water) and Yersinia enterocolitica (present in 4.3% of incoming
water samples and 1.1% of outgoing water) did not find favorable conditions for
growth on the ion exchange resins.
PMID- 9636987
TI - [Microbiologic/hygienic evaluation of the risk potential of bacteria from soil
and water sources in combination with biotechnologic risks of soil restoration].
AB - Biological cleanup-processes removing contaminations from soil and ground-water
can be carried out "ex-situ" or "in situ". The pollutants are mineralized
(totally or partly) by microorganisms. The successful application of
bioremediation techniques often leads to an increase of aerobic and facultatively
anaerobic bacteria in soil and/or groundwater, a fact that triggered discussions
about a potential biological risk originating from these microorganisms. In this
study the identification results of 10,200 microorganisms isolated from 109
ground-water- and 152 soil-samples of different sites contaminated with mineral
oil or chlorinated aromatics are evaluated with respect to a possible biological
risks originating from these microorganisms. According to their biological risk
potential, 19.2% (1958) of the isolated organisms can be grouped into risk-groups
II, that means they they are able o cause human disease but it is unlikely that
they are spread to the community and there is effective prophylaxis or treatment
available. The majority of isolates (81.8%) are grouped into risk group I,
meaning that it is very unlikely that they cause a human disease. All these
microorganisms are either adsorbed to the soil-matrix or within a closed system
of a water-treatment-plant, so that the risk of infection is very unlikely for
healthy individuals (regarding possible pathways of infection). The risk
potential in waste-water-treatment-plants is regarded to be significantly higher
than in biological soil-cleanup processes, because of the specific origin of the
bacteria and the possible formation of aerosols.
PMID- 9636988
TI - [Insertion possibility of 16S-23S space amplification and random amplified
polymorphic DNA analysis for typing of methicillin-resistant Staphylococcus
aureus strains in the context of nosocomial infections].
AB - Within the scope of the present study n = 183 MRSA isolates from the extended
area of Dusseldorf and n = 93 international MRSA strains from seven different
countries were typed by pulsed-field gel electrophoresis and two PCR methods
(RAPD and 16S-23S-spacer amplification). The isolates could be subdivided into 30
different types by PFGE, into 21 by means of RAPD and 18 by 16S-23S-spacer
amplification. PFGE had the highest discriminatory potential, however, a combined
use of the three typing methods allows a more detailed differentiation even of
those isolates with identical PFGE pattern. Both amplification procedures were
rapid, easy in handling with reproductable results. For a temporary
epidemiological analysis within 24 hours, both amplification methods could be
combined. In case the investigated isolates were still suspected of showing a
"clonal identity", they should be analysed by additional PFGE (lasting about four
days). Although the international isolates were chosen by random selection,
several MRSA strains with identical pattern could be found in different countries
of the world. Some RAPD-, spacer- and PFGE pattern were constant over many years.
This reflects a high genetic stability of single strains.
PMID- 9636989
TI - Nonhemolytic strains of Listeria monocytogenes detected in milk products using
VIDAS immunoassay kit.
AB - In December 1995 detection of Listeria monocytogenes Sv 1/2a in milk products
that were routinely sampled for investigation at the Austrian Federal Food
Inspection Laboratory (Vienna) led the food manufacturer in question to withdraw
his product from the market. While one of seven Listeria strains isolated from
this food product using "VIDAS L. monocytogenes kit" was undoubtedly L.
monocyotogenes, six strains were nonhemolytic. In classical bacteriology
haemolysin is used as an important phenotypic property to differentiate L.
monocytogenes from the apathogenic L. innocua species. Species identification by
PCR and by Western blotting confirmed that all nonhemolytic strains were indeed
L. monocytogenes. Our confirmation of nonhemolytic isolates as true L.
monocytogenes strains underlines the considerable potential of the VIDAS system
as a specific immunological easy-to-use and automated test kit for detection of
L. monocytogenes in food products. Whether or not the presence of non-hemolytic
Listeria monocytogenes in food products justifies legal actions should be
addressed by the proper authorities.
PMID- 9636990
TI - Application of automated thermal disinfection instead of sterilisation procedures
for treatment of rotating dental instruments: efficacy against viruses?
AB - In dentistry it is of primary importance to take into consideration microbial
transfer due to the nature of the construction of rotating dental instruments.
This aspect was the starting point for our research with the question whether or
not sterilisation is fundamentally necessary for slow and high speed hand pieces
to make them "safe" out of a virological point of view, or whether a thermal
disinfection could also possibly be adequate for this purpose. In this context,
we tested the efficiency of the cleaning and disinfection capacity of an
automated steam disinfection and sterilisation unit (Sirona Hygiene Center,
Siemens, AG, Bensheim) intended to the hygienic treatment of dental instruments
with respect to viruses. In model tests the corresponding instruments were
experimentally infected with herpes simplex virus type 1 (HSV) and simian
vacuoling virus (SV40). As indicator systems we used for both cell cultures
(measurement of the degree of infectiosity) and (for HSV) polymerase chain
reactions (PCR; determination of viral nucleic acids). In the tests for
(residual) infectiosity after thermal disinfection (as an isolated step of the
Hygienic Centre) and also for a combination of cleaning and subsequent thermal
disinfection (also after protein application), no infectious virus could be found
in the interior of the slow handpieces and turbines tested. In opposite to this,
infectious HSV and SV40 could be found after completion of every isolated
cleaning program in the turbine (in all three ducts) and in the slow handpiece
(only in the gearbox duct in the case of HSV, and in the case of SV40 also in the
water and air ducts in very small amounts). The PCR analyses showed that no
nucleic acids could be found in both instruments (in the air and water ducts)
following a practice-relevant combination of cleaning and disinfection, but that
PCR-positive signals were obtained for the larger-volume gearbox and drive and
return air ducts in 1 or 2 of 3 test samples. The detection of viral nucleic acid
proves that it is not a matter of complete removal of the infectious agents from
the instruments, but rather that they are simply inactivated. Since the test
samples did not show similar amounts of viral nucleic acid, it demonstrates the
strong influence of the basic parameters (efficiency of the virus contamination,
flushing conditions and the like). Our experimental model demonstrate that
thermal disinfection may be adequate to prevent virus contamination of rotating
dental instruments, while compulsory sterilisation is not mandatory. Further
studies are necessary to demonstrate whether the present data are applicable for
rotating dental instruments from other manufactures.
PMID- 9636991
TI - [Can the DGHM test for the surgical hand disinfection be used to detect residual
effects?].
AB - It is investigated if the log reductions measured by the DGHM test for
examination and evaluation of disinfecting procedures for the surgical hand wash,
i.e. the short and long term values RFreference, 0h, RFreference, 3h,
RFpreparation, 0h and RFpreparation, 3h can be used to detect residual effects (a
remanent action) of the tested preparation. To do this the differences delta RF =
RF0h-RF3h of reference and tested preparation have been formed which are a
measure for the bacterial regeneration rate. A remanence index RI = magnitude of
delta RFreference/magnitude of delta RFpreparation has been specified, which, in
case RI > 1 indicates a residual effect of the test preparation in relation to
the reference. The evaluation of 21 testing protocols is showing that the
calculated remanence indexes are far away from any significance. This is
attributed on the one hand to the great standard deviations of the log reductions
and on the other hand to virtually only small residual effects of the tested
preparations.
PMID- 9636993
TI - A tetrahedral zinc(II) complex of tris(2-pyridylethyl)amine.
AB - The zinc ion in the title complex, [N,N'-bis(2-pyridylethyl)-2-(2
pyridyl)ethylamine-kappa 4N]zinc(II) diperchlorate, [Zn(C21H24N4)](ClO4)2,
displays a distorted tetrahedral configuration. The Zn-Npy distances range from
1.979 (5) to 1.999 (5) A, while the Zn-Namine distance is 2.028 (5) A. The Npy-Zn
Npy and Npy-Zn-Namine angles range from 111.9 (2) to 119.6 (2) degrees and from
102.3 (2) to 103.4 (2) degrees, respectively. This behavior contrasts with the
five-coordinate geometry normally observed in tripodal ligands of similar
structure, and can be ascribed to the presence of weakly-coordinating anions and
the ligand-metal chelate-ring size.
PMID- 9636992
TI - [Current data and questions on the carcinogenicity of solid particles of diesel
engine exhaust and other sources].
AB - During the last few years, the findings could be confirmed which led to the
conclusion that very fine solid particles which are not known to have an
intrinsic toxicity, can induce lung tumours in rats. The carcinogenic potency
seems to increase parallel to increasing specific surface area and decreasing
particle size. However, many questions remain open. Organic compounds which
contain many carcinogenic polycyclic aromatic hydrocarbons (PAH) can explain only
less than 1% of the carcinogenic effect of diesel exhaust in the rat lung.
Therefore, the carcinogenicity of diesel exhaust cannot be reduced by an
oxidizing catalyst. It burns a part of the organic substances adsorbed on the
surface of the carbonaceous core of diesel particles and thus helps to follow the
low standard for particles in diesel emissions, but without reduction of the
carcinogenic potential because it does not reduce the emission of the insoluble
carcinogenic part of the particles, the elementary carbonaceous core. The search
for a hypothetical threshold for the carcinogenicity of particles in the rat lung
aims at the determination of mechanisms which are preconditions for the
development of a tumour. If certain doses do not induce such lesions they are
considered safe. Chronic inflammation, proliferation of epithelial cells and
fibrosis are discussed to be preconditions. However, the pathways which lead to
inflammation and proliferation could proceed independent of the molecular
carcinogenesis. Therefore, a cancer risk from diesel particles and other very
fine particles may occur under environmental conditions. If the positive
epidemiologic studies are relevant, a lung cancer risk for humans can be
calculated which is higher than that calculated from inhalation studies with
rats.
PMID- 9636994
TI - endo-endo-anti Diels-Alder diadduct of hexachlorocyclopentadiene with 1,6
dioxacyclodeca-3,8-diene.
AB - There are two independent molecules of endo-endo-anti
1,7,8,9,10,16,17,18,19,19,20,20-dodecachloro-4,13-
dioxapentacyclo[14.2.1.1(7,10).0(2,15).0(6,11)]icosa-8,17-di ene, C18H12Cl12O2,
in the unit cell with different conformations. In one, the ten-membered ring
adopts a chair-chair conformation, and in the other, it adopts a distorted chair
chair conformation. There are near-zero torsion angles at the ring-fusion bonds
in both forms [1.5 (6) and 8.1 (5) degrees in the chair-chair molecule, and 2.9
(5) and 2.5 (5) degrees in the distorted chair-chair molecule]. The torsion
angles about the bonds comprising the sides of the chair-chair are 158.5 (3),
160.7 (3), -146.8 (4) and 155.7 (3) degrees, and those of the distorted chair
chair are 148.0 (3), -146.8 (3), 175.7 (3) and -52.3 (4) degrees. The norbornene
C=C bonds have lengths of 1.314 (6) and 1.305 (6) A in the chair-chair molecule,
and 1.309 (6) and 1.318 (6) A in the other. The four dioxolane-system O-C bonds
have average lengths of 1.411 (5) and 1.421 (5) A in the two independent
molecules.
PMID- 9636996
TI - Effects of tumor necrosis factor alpha (TNF alpha) on the phospholipid metabolism
of Tetrahymena pyriformis.
AB - The effect of (0.05 ng ml-1 and 0.1 ng ml(-1)) TNF alpha on the phospholipid
metabolism of Tetrahymena pyriformis was studied. The amount of phosphatidyl
choline (PC), phosphatidyl inositol (PI), phosphatidic acid (PA), phosphatidyl
ethanolamine (PE), diacylglycerol (DAG), arachidonic acid (AA) and ceramide was
higher, but the phosphatidyl inositol 4 phosphate (PIP) and phosphatidyl inositol
bis-phosphate (PIP2) as well, as sphingomyelin (SM) content was lower in TNF
alpha-treated cells than in the controls. In the culture medium (secreted forms)
this situation was reversed. There were differences in the results gained by
incorporation of [3H]-palmitic acid or 32P into the phospholipids. To control the
functional effects of TNF alpha in Tetrahymena, the rate of cell division, the
condensation of chromatin, the viability of cells and morphometrical values have
been studied. The cytokine reduced cell growth, altered morphometric indices and
increased chromatin condensation, however cell viability was not influenced. The
results demonstrate the effects of TNF alpha at a low level of evolution, what is
realized by changes in the phospholipid metabolism participating in signalling
pathways.
PMID- 9636995
TI - Activation and glucagon regulation of mitogen-activated protein kinases (MAPK) by
insulin and epidermal growth factor in cultured rat and human hepatocytes.
AB - Many hepatocellular activities may be proximally regulated by intracellular
signalling proteins including mitogen-activated protein kinases (MAPK). In this
study, signalling events from epidermal growth factor (EGF) and insulin were
examined in primary cultured human and rat hepatocytes. Using Western
immunoblots, rat and human hepatocytes were found to produce a rapid tyrosine
phosphorylation of the EGF receptor and MAPK following 0.5-1 min exposure to EGF.
Phosphorylation of p42 and p44 MAPK was observed following 2.5 min exposure to
EGF. Insulin treatment produced phosphorylation of the insulin receptor beta
subunit; she phosphorylation was not observed. MAPK phosphorylation corresponded
with a shift in molecular weight and an increase in kinase activity. Insulin
dependent activation of MAPK was unequivocally observed only in human
hepatocytes, though a slight activation was detected in rat. Co-treatment with
insulin and EGF produced phosphorylation and complete electrophoretic shift in
molecular weight of MAPK, with an additive or synergistic increase in enzyme
activity in rat but not human hepatocytes; human hepatocyte MAPK was maximally
stimulated by EGF alone. Glucagon pretreatment blocked phosphorylation, gel
mobility shift and kinase activity of MAPK induced by insulin but only partially
blocked EGF-induced MAPK activation in human hepatocytes. Glucagon also reduced
the activation of MAPK by EGF in rat hepatocytes. Pre-treatments with forskolin
or cyclic AMP analogues diminished in the insulin-, EGF- and insulin plus EGF
dependent activation of MAPK in rat hepatocytes without effecting phosphorylation
of receptors or MAPK. These results indicate that although EGF and insulin may
both signal through the MAPK/ras/raf/MAPK pathway, the response for MAPK differs
between these ligands and between species. Further, in both rat and human,
glucagon exerts its effects through a cyclic AMP-dependent mechanism at a level
in the insulin and EGF signal transduction pathways downstream of MAPK but
promixal to MAPK. The partial inhibition of EGF-induced MAPK phosphorylation by
glucagon in human hepatocytes provides further evidence for a raf-1-independent
pathway for activation of MAPK.
PMID- 9636997
TI - Occurrence of the Crabtree effect in HeLa cells.
AB - The occurrence of a Crabtree effect in HeLa cells was detected. Some properties
of pyruvate kinase (PK) were also evaluated. Hexose phosphate, triose-phosphate
and phosphoenolpyruvate (PEP) significantly decreased the oxygen consumption of
digitonin-permeabilized HeLa cells, which were oxidizing succinate. The Crabtree
effect promoted by PEP was concentration-dependent and was lowered by an increase
of ADP concentration, suggesting a participation of PK. The dependence of
fructose-1,6-bisphosphate (FDP) by HeLa cell PK was observed. The PK of HeLa
cells was inhibited by L-alanine only in the absence of FDP, while in the
presence of the metabolite, an increase in the activity was observed. PK was also
inhibited in the presence of L-histidine and L-leucine, while L-serine promoted
activation. L-Cysteine and L-phenylalanine also inhibited the PK of HeLa cells.
This, together with the sigmoidal character in relation to substrate
concentration, suggests the presence of the K-type of PK in HeLa cells.
PMID- 9636998
TI - Activation of bullous pemphigoid antigen gene in mouse ear epidermis by
ultraviolet radiation.
AB - Bullous pemphigoid (BP) is an autoimmune blistering disease and is a
photoaggravated dermatosis, but the mechanism of the aggravation is still
unknown. Since damage to DNA initiates transcription of some genes, we
investigated in epidermis of mouse ears the relationship between DNA damage by
ultraviolet (UV) radiation and BP antigen (BP-Ag) gene activation. For this,
albino male mice were irradiated with 254 nm wavelength UV for a total dose of
500 J m-2. At fixed times (0.5, 2, 24, 48 and 72 h) post-UV irradiation, mouse
ears were cut off, frozen and sectioned. In the sections, it was found that
immunohistochemically detectable pyrimidine dimers were observed in nuclei of all
epidermal cells at 0.5 h that were almost repaired by 72 h; a frequency of single
strand breaks in DNA detected by in situ nick translation started to increase in
nuclei of all epidermal cell layers at 0.5 h and the increase continued up to 24
h; mRNA for BP-Ag localized by non-radioactive in situ hybridization appeared in
nuclei of basal cells at 0.5 h and in both nuclei and cytoplasm at 2 h; and
immunoreactive BP-Ag started to increase in the basal cell cytoplasm and in the
basement membrane zone at 2 h. BP-Ag started to accumulate in the basement
membrane zone at 2 h. It is suggested that UV radiation increased BP-Ag synthesis
through BP-Ag synthesis through BP-Ag gene activation and that this reaction is a
factor which aggravates BP following UV irradiation in BP patients.
PMID- 9636999
TI - Genomic instability associated with myotonic dystrophy does not involve p53
expression and activity.
AB - We tested the hypothesis that the instability of the trinucleotide CTG at the
myotonic dystrophy (DM) locus could be an intrinsic DNA damage recognisable by
the p53 cell-cycle checkpoint system. p53 mRNA and protein levels were assayed in
muscle biopsies and fibroblast cell lines of DM patients and unaffected controls.
No differences in mRNA and protein levels were found between patients and
controls, regardless of their expansion size. However, in the cells treated with
adryamicin, p53 protein levels were comparable in DM and control cells. We
conclude that the CTG trinucleotide expansion within the myotonin gene does not
activate the p53 surveillance system, at least in adult tissues. The escape of
trinucleotide expansion from the p53-mediated DNA repair system could explain
some of the biological characteristics of genome instability.
PMID- 9637000
TI - A chemical modification of myeloperoxidase and lactoperoxidase with 2-(O
methoxypolyethylene glycol)-4, 6-dichloro-s-triazine (activated PEG1).
AB - The modification of myeloperoxidase and lactoperoxidase with 2-(O
methoxypolethylene glycol)-4, 6-dichloro-s-triazine, an activated polyethylene
glycol (PEG1), was investigated. The modification caused a shift of the Soret
band in the light absorption spectrum, from 430 nm to 418 nm in the case of
myeloperoxidase (native ferric form), and from 412 nm to 406 nm in the case of
lactoperoxidase (native ferric form). PEG1-modified myeloperoxidase and PEG1
modified lactoperoxidase both failed to bind with antiserum to the respective
native enzyme, but both retained respectively 4.5 +/- 0.3 per cent (mean +/- SE,
n = 5) and 0.6 +/- 0.2 per cent (mean +/- SE, n = 5) of the activities of
peroxidation of the hydrogen donor o-methoxyphenol in comparison with the native
enzyme, and 1.5 +/- 0.2 per cent (mean +/- SE, n = 5) and 1.2 +/- 0.2 per cent
(mean +/- SE, n = 5) of the activities of destruction of fuchsin basic in the
presence of hydrogen peroxide and a halide, bromide. The pH dependencies of the
peroxidating activities were almost the same as those of the corresponding native
enzymes, but both the optimal pHs of the reactions involving the destruction of
fuchsin basic were shifted by approximately 1.0 pH unit toward neutral pH
compared with the respective native enzymes.
PMID- 9637001
TI - The expression of alpha 2 beta 1 integrin and alpha smooth muscle actin in
fibroblasts grown on collagen.
AB - The maturation of connective tissue involves the organization of collagen fibres
by resident fibroblasts. Fibroblast attachment to collagen has been demonstrated
to involve cell surface receptors, integrins of the beta 1 family. Integrins are
associated with cytoplasmic actin of microfilaments either directly or through
focal adhesions. The major actin isoform of fibroblast microfilaments is beta
actin and to a lesser extent alpha smooth muscle (alpha SM) actin. Cultured human
dermal fibroblasts derived from adult dermis, newborn foreskin or keloid scar
were grown on either uncoated or collagen-coated surfaces. The expression and
synthesis of both alpha 2 beta 1 integrin and alpha SM actin were followed by
immunohistology and immunoprecipitation. Fibroblasts on uncoated surfaces
expressed little alpha 2 beta 1 integrin on their surface, while 20 per cent of
them demonstrated alpha SM actin within microfilaments. Fibroblasts grown on a
collagen-coated surface minimally expressed alpha SM actin in microfilament
structures and a majority of the cells were positive for alpha 2 beta 1 integrin
on their membranes. Using [35S]-methionine incorporation and immunoprecipitation,
it was shown that fibroblasts grown in uncoated dishes synthesized more alpha SM
actin than fibroblasts grown on collagen-coated dishes. In contrast, fibroblasts
grown on collagen coated dishes synthesized more alpha 2 beta 1 integrin compared
to the same cells grown on uncoated dishes. Fibroblasts maintained on a type I
collagen upregulate the expression and synthesis of alpha 2 beta 1 integrin, and
downregulate the expression and synthesis of alpha SM actin.
PMID- 9637002
TI - Inactivation of urate oxidase by a system composed of lactoperoxidase, hydrogen
peroxide and bromide.
AB - Urate oxidase from Candida utilis, an enzyme containing an essential thiol, was
examined for its sensitivity to lactoperoxidase, an oxidant present in breast
milk. Upon exposure to a system composed of lactoperoxidase, hydrogen peroxide
and bromide at moderately alkaline pH, the urate oxidase exhibited comparable
activity to the untreated enzyme; but upon exposure at moderately acidic pH, it
lost its activity completely. Thus the lactoperoxidase-H2O2-bromide system
significantly inactivated urate oxidase only at moderately acidic pH. This
inactivation was prevented by the presence of N-acetylmethionine, a methionine
analogue, or glutathione, which is a thiol compound analogous to an amino acid,
indicating that it was probably due to the oxidation and damage of the methionine
residue and/or the thiol group in the urate oxidase by the lactoperoxidase
system, that loss of catalytic activity of the urate oxidase occurred.
PMID- 9637003
TI - Ribosomes mask cytochrome b5 on rough microsomal vesicles.
AB - Cytochrome b5 is unmasked on the removal of ribosomes by chemical degranulation
of rat liver microsomes. Reattachment of ribosomes to stripped membranes remasks
this enzyme on the membrane surface. This haemoprotein may be involved either in
the attachment of ribosomes to reticular membranes or in protein biosynthesis by
membrane-bound ribosomes.
PMID- 9637004
TI - Levels of toxaphene indicator compounds in fish meal, fish oil and fish feed.
AB - Three toxaphene indicator compounds were determined in fish oil and fish meal of
different origin and raw material as well as in feed containing fish oil and fish
meal. Fish oil and fish meal from South America contained no or only traces of
the indicator congeners. The sum of the three compounds varied in fish oils from
Europe between 13 micrograms/kg fat (sand eel oil) and 206 micrograms/kg fat (cod
oil). Varying concentrations were also determined in European fish meal and in
feed. Toxaphene indicator compounds were as well detected in trout and salmon fed
with toxaphene residues containing feed. Results indicate that feed can
contribute to toxaphene contamination of farmed salmon from Europe.
PMID- 9637005
TI - Organochlorine pesticides and PCBs in human milk collected from mothers nursing
hospitalized children.
AB - Organochlorine compounds in milk were analyzed in samples collected over a nine
year period (1987-1995) from nursing mothers (N = 139) whose children were
hospitalized for various disorders. All samples contained p,p'-DDE and PCBs; the
median concentrations were 318 micrograms/kg milk fat and 220 micrograms/kg milk
fat resp. Higher levels were found in mothers (N = 12) nursing neonates with
impaired neurodevelopmental competencies or an inappropriate arousal reaction. No
difference was observed between mothers nursing children with respiratory or
gastrointestinal diseases, urinary tract infections or other infectious diseases,
anemias, prolonged neonatal hyperbilirubinaemias or when children were with
dermatological findings, congenital malformations or healthy.
PMID- 9637006
TI - Pentachlorophenol and phenanthrene biodegradation in creosote contaminated
aquifer material.
AB - Contamination of the subsurface environment at the Libby Superfund Site, Montana,
includes polycyclic aromatic hydrocarbons and f1p4achlorophenol due to accidental
spills and improper disposal of wood preserving wastes. Biodegradation is a
treatment technology gaining wide application in the treatment of hazardous waste
sites. A microcosm study was conducted to evaluate the effect of temperature,
sampling depth, nutrient addition, and oxygen on the biodegradation potential of
phenanthrene and pentachlorophenol in aquifer samples using radiolabeled
chemicals. Mineralization of phenanthrene reached 14% but was less than 1% for
pentachlorophenol over the 56 day incubation period. Phenanthrene mineralization
in microcosms at 10 degrees C was not significantly different from those at 20
degrees C. This may have been due to microbial community acclimation to lower
temperatures at the site. Average volatilization was less than 2% for both
phenanthrene and pentachlorophenol. After 56 days, most of the radiolabeled
chemical was either solvent extractable or soil bound.
PMID- 9637007
TI - Application of an automated HS-GC method in partition coefficient determination
for xylenes and ethylbenzene in rat tissues.
AB - An automated static head space-gas chromatography method was used in the
determination of partition coefficients (Kd) for the xylene isomers and
ethylbenzene in blood, brain, muscle, kidney, liver and fat of Sprague Dawley
rats. Since homogenization resulted in the potential loss of analytes from tissue
samples, unhomogenized samples were used. With a few exceptions, tissue:air Kd
values were independent of the concentrations of the analytes, singly or as a
mixture. The tissue:blood Kd values were determined. For each tissue and analyte,
the value obtained for each analyte concentration was within +/- 10% of the mean
value calculated for the entire concentration range.
PMID- 9637008
TI - Methanogenic bacteria: presence in foodstuffs.
AB - Methanogenic bacteria are anaerobic, oxygen-intolerant microorganisms, and it is
only by studying the different habitats of such bacteria that fundamental
information about their ecology becomes available. This research has evaluated
methanogenic bacteria in apparently aerobic ecosystems, in foodstuffs not
subjected to chemical-physical reclamation processes, where the presence of
methanogenic bacteria has never been investigated. Methanogenic bacteria,
ascribable to the Methanogenium, Methanobacterium and Methanosarcina genera, were
found in vegetables, meat, fish and cheese but were generally absent in
confectionery products and fruit. The microorganisms appear to be chance
contaminants, usually being present in only very low numbers. It should be noted
that none of the tested foods showed the presence of Methanobrevibacter smithii,
M. oralis or Methanosphaera stadtmaneae, methanogenic bacteria sometimes present
in the human digestive tract.
PMID- 9637009
TI - Effect of different starches on Escherichia coli (S1) beta-glucuronidase
expression.
AB - Studies with pure cultures growing in laboratory media indicated that beta
glucuronidase expression of Escherichia coli S1 was considerably affected by
starch added to the medium as the only carbon source. This result, which may be
an aspecific modulation of enzyme expression, was independent of the starch
molecular structure and effects were analogous for maize, rice, wheat or potato
starches. It was observed that enzyme expression was little affected by the
growth rate. The beta-glucuronidase activities of starch-grown bacteria found in
the present study agree with those observed in animal and human models performed
for in vivo evaluation of effects of dietary starch effects on gut microbial
ecosystems.
PMID- 9637010
TI - New shuttle vectors for Rhodococcus sp. R312 (formerly Brevibacterium sp. R312),
a nitrile hydratase producing strain.
AB - Two shuttle vectors named pRC52 (10.7 Kb) and pRK52 (12.2 Kb) carrying
chloramphenicol (Cm) and chloramphenicol plus kanamycin (Km) resistance genes,
respectively, were constructed by fusion of a cryptic plasmid pBL13869 (replicon
pBL1, 5.8 Kb) from Brevibacterium lactofermentum ATCC13869 with pBR328 E. coli
plasmid. Transformation of Rhodococcus sp. R312 (formerly Brevibacterium sp.
R312) protoplasts was realised with an efficiency of 28 transformants per
micrograms of DNA.
PMID- 9637011
TI - Effect of osmotic stress on glucose oxidase production and secretion by
Aspergillus niger.
AB - A mycelium of Aspergillus niger was cultured under various osmotic stresses. When
fungus was cultured under osmotic stress, total catalase activity increased with
increasing concentration of NaCl, up 0.4 M, but glucose oxidase under this
condition significantly decreased. Mycelial growth was repressed with increased
media osmolarity. To release periplasmic glucose oxidase 72-h old mycelium was
suspended on a concentrated solution of NaCl (0.4-2.8 M/l). The highest yield of
GOD activity was obtained at a NaCl concentration of 1.2 M at pH 6.0, which
improved the activity of this enzyme by about 2.1-fold in comparison with the
control medium without this depressor.
PMID- 9637012
TI - Continuous ethanol production from sugarcane molasses using a column reactor of
immobilized Saccharomyces cerevisiae HAU-1.
AB - A fermentation system for the continuous ethanol production from sucrose and
molasses using calcium alginate immobilized Saccharomyces cerevisiae strain HAU-1
has been optimised. Immobilization of active yeast cells (30%, w/v) was
accomplished in 1.5% calcium alginate and these yeast-beads were employed for
ethanol production in a vertical column reactor. High ethanol productivity was
achieved with a medium containing 10%, w/v sucrose at a dilution rate of 0.20 h
1. Alginate beads containing 30-50% yeast cell--mass resulted in high
productivity 60.4 g l-1 h-1). Sugarcane molasses containing 15% total sugars was
fermented in column reactor to produce 6.0%, v/v ethanol in continuous system.
These yields could be improved to 7.0% with overall 11% increase in fermentation-
efficiency with the use of acid-clarified sugar cane molasses medium.
PMID- 9637013
TI - The isolation of Pseudomonas and other Gram(-) psychrotrophic bacteria in raw
milks.
AB - In this research, totally 200 raw milk samples in different areas of Ankara were
collected from various dairy plant. The isolated psychotrophic bacteria from the
raw milk samples are the species of Pseudomonas spp., Acinetobacter spp.,
Alcaligenes and Aeromonas. Isolation of Pseudomonas and other gram(-)
psychrotrophic bacteria types are determined as P. aeruginosa 11 (5.5%), P.
putida 11 (5.5%), P. fluorescens biotype I 10 (5.0%), P. fluorescens biotype II 4
(2.0%), P. fluorescens biotype III 6 (3.0%), P. aurefaciens 2 (1.0%), P.
pseudomallei 3 (1.5%), P. cepacia 1 (0.5%), A. calcoaceticus lowffii 5 (2.5%), A.
calcoaceticus anitratum 4 (2.0%), A. faecalis 3 (1.5%) and A. hydrophilia 1
(0.5%).
PMID- 9637014
TI - Toxin production by pathovars of Pseudomonas syringae and their antagonistic
activities against epiphytic microorganisms.
AB - 75 strains of 21 various Pseudomonas syringae (P.) pathovars were investigated in
different tests for their toxin production. Data from literature about the
production of the known phytotoxins phaseolotoxin (pv. phaseolicola), tabtoxin
(pv. coronafaciens, pv. tabaci), coronatine (pv. atropurpurea, pv. glycinea, pv.
maculicola, pv. morsprunorum, pv. tomato), and toxins of the lipodepsipeptide
group (pv. aptata, pv. atrofaciens, pv. syringae) could be confirmed. Besides, a
production of the phytohormone ethylene was detected for P. phaseolicola isolates
from kudzu (Pueraria lobata) and for all tested P. glycinea and P. cannabina
strains. Strains of P. apii, P. aptata, P. atrofaciens, and P. tomato produced
antimetabolic toxins which could be detected with an agar diffusion assay with
Escherichia coli as indicator strain. These antimetabolites inhibit a step in the
arginine/ornithine biosynthesis. P. maculicola strains caused inhibition zones in
this assay which could not be reversed by the tested amino acids. All strains
with inhibitory effect against E. coli and Geotrichum candidum were also proved
for their antagonistic activity against a selection of typical phyllosphere
microorganisms. Most of the phytotoxins possess antimicrobial activity with
different spectrum and efficiency. Only the lipodepsipeptide-producers showed
antifungal activities. Our results show that the production of toxins is a
widespread property among Pseudomonas syringae pathovars, and that some pathovars
can produce more than one toxin. This characteristic and the antimicrobial
activity of most toxins could be of advantage for the toxin-producing bacteria to
adapt to different habitats.
PMID- 9637015
TI - Partial purification of an iron-dependent L-serine dehydratase from Clostridium
sticklandii.
AB - An oxygen-sensitive and highly unstable L-serine dehydratase was partially
purified from the Gram-positive anaerobe Clostridium sticklandii. The final
active preparation contained five proteins of 27, 30, 44.5, 46, and 58 kDa as
judged by SDS-PAGE. The N-terminal sequence of the 30 kDa subunit showed some
similarity to the alpha-subunits of the iron-containing L-serine dehydratases
from Clostridium propionicum and Peptostreptococcus asaccharolyticus. Oxygen
inactivated L-serine dehydratase from C. sticklandii was reactivated by
incubation with Fe2+ under reducing conditions. Furthermore, the enzyme was
inactivated by iron-chelating substances like phenanthroline and EDTA. Pyridoxal
5-phosphate (PLP) did not stimulate the activity, and known inhibitors of PLP
containing enzymes such as NaBH4 had no effect on the activity of L-serine
dehydratase from C. sticklandii.
PMID- 9637016
TI - Determination of histamine and leukotrienes from basophils in cell supernatants
by high-performance liquid chromatography.
AB - A reversed-phase high-performance liquid chromatographic method with gradient
elution for the separation of the mediator substances histamine and the
leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) is described. The detection
occurs fluorimetrically after automated precolumn derivatization with o
phthaldialdehyde. All components are chromatographically separable. Because of
the different excitation and emission wavelengths, only the most important
biological active mediators histamine and LTC4 are determinable in one parallel
chromatographic run. The method is examined by linearity and precision tests and
is applicable to biological sample matrices like cell supernatants of human
basophils enriched by Percoll-density gradient centrifugation and stimulated for
mediator release by anti-IgE. The established method is suitable to separate the
mediators from other matrix components. The determination limit for histamine is
55.0 micrograms/L and that for LTC4 16.0 micrograms/L, referring to the reference
solutions. Therefore, a fast, economical method for the common determination of
the most important mediators histamine and LTC4 is established. This method is
also suitable for high sample amounts in routine medical analysis.
PMID- 9637017
TI - Isolation and recovery of 2-aminoethanol, N-methyl-2-aminoethanol, and N,N
dimethyl-2-aminoethanol from a copper amine aqueous matrix and from amine-treated
sawdust using liquid-liquid extraction and liquid-solid extraction combined with
capillary gas chromatography-ion-trap mass spectrometry.
AB - An analytical method for the rapid isolation and recovery of the homologous
series of 2-aminoethanols, a class of organic compounds of importance to wood
preservative treatment, is successfully developed. The method is applied to an
aqueous solution of copper amine (copper[II] hydroxide complexed
monoethanolamine) and to copper-amine-treated sawdust. The method incorporates a
gas chromatograph-ion-trap mass spectrometer. A discussion of the secondary
equilibrium effects involved when ionizable analytes are extracted from an
aqueous phase with respect to organic bases is presented. Using 2-propanol as the
extractant coupled to a salt-saturated aqueous phase results in recoveries of 63%
for 2-aminoethanol, 51% for N,N-dimethyl-2-aminoethanol, and 56% for N-methyl-2
aminoethanol for a single liquid-liquid extraction. The choice of 2,2,2
trifluoroethanol as an internal standard is found to be quite suitable. A
comparison of the precision and accuracy for an external versus an internal mode
of instrument calibration demonstrates that the internal standard mode is
preferable for this manual injection.
PMID- 9637018
TI - High-performance liquid chromatographic analysis with diode-array detection of
bradykinin, neuropeptide K, and substance P in human plasma.
AB - A method is described for the determination of bradykinin, neuropeptide K (NPK),
and substance P in patients with atypical carcinoid syndrome. The developed
method uses a combination of conventional and solid-phase extraction as well as
high-performance liquid chromatographic techniques. A narrow-bore C18 column with
ultraviolet detection is used (200 nm). The technique recovers bradykinin at a
level of 98%, NPK at 96%, and substance P at 98% (when pure standards are
dissolved) at concentration levels relevant to the atypical carcinoid syndrome.
In biological samples, the recovery rate of bradykinin, NPK, and substance P
drops to 88, 86, and 88% respectively. The overall analysis time is 150 min from
receipt of samples. This method proves to be a valuable tool in the
identification of neuropeptides and thus the diagnosis of atypical carcinoid
syndrome, especially in puzzling cases with nonspecific symptoms.
PMID- 9637019
TI - The magic of hypnosis: is it child's play?
AB - Hypnosis is often disregarded and undervalued because it cannot be currently
explained by natural science or scientific method. An alternative existential
psychology paradigm, specifically an existential-phenomenological model, is
offered here to close the gap between the theoretical and the actual clinical
practice of hypnosis. This existential-phenomenological model emphasizes the
individual's experience over any preconceived notions or diagnoses. In this
context, the author introduces and discusses the idea that perception prefigures
embodiment, creating the power of suggestion. And children's greater overall
hypnotic susceptibility is explained as a result of natural unbiased observations
of the world, free of the mind-body split that adults apply to perception.
PMID- 9637020
TI - Time perspective: temporal extension, time estimation, and impulsivity.
AB - It has been proposed that time perspective is an important variable that can, in
part, explain the differences between people in terms of the development of self
control. One corollary of this position is that time perspective is somehow
related to systematic biases in the way people perceive the passage of time. Such
a bias may or may not be augmented by an association between time perspective and
impulsivity. Two studies were conducted using measures of temporal extension,
time estimation, and impulsivity. In general, no consistent effects were found.
Neither time perspective nor impulsivity was related to any characteristic
pattern of errors. In the second study, time perspective (mediated by age) was
associated with predicting very brief time estimation scores, but not longer time
estimation periods. It was concluded that whatever the mechanism might be that
underlies the purported effect between time perspective and self-control, it is
not related to a differential ability to perceive time moving more or less
quickly.
PMID- 9637021
TI - Attitudinal predictors of dissociation: hostility and powerlessness.
AB - The relationship between dissociative tendencies and attitudes relating to
aggression and powerlessness was investigated in a sample of 106 Australian
psychology students. Dissociation was positively related to aspects of aggression
and in particular to an attitude of hostility. Respondents' perceptions of their
own powerlessness did not predict proneness to dissociative experiences. The data
are consistent with the view that trauma-engendered attitudes and affects may be
markers of the development of dissociative tendencies.
PMID- 9637022
TI - Self-Deceptive Enhancement and Impression Management correlates of EPQ-R
dimensions.
AB - The Self-Deceptive Enhancement and Impression Management scales of the Paulhus
(1991) Balanced Inventory of Desirable Responding were correlated with the
Psychoticism, Neuroticism, Extraversion, and Lie scales of the Eysenck EPQ-R
(Eysenck & Eysenck, 1991) in a student sample. Extraversion correlated positively
and Neuroticism correlated negatively with Self-Deceptive Enhancement, whereas
Psychoticism correlated negatively and the Lie scale correlated positively with
Impression Management. These findings suggest that the EPQ-R scales are involved
in different aspects of socially desirable responding. It was concluded that
social desirability should not be controlled in measures of Extraversion and
Neuroticism but it should be controlled in measures of Psychoticism.
PMID- 9637023
TI - Physiological mechanisms of sexual dysfunction side effects associated with
antidepressant medication.
AB - Sexual dysfunction side effects have been associated with antidepressant
medication, especially with serotonin reuptake inhibitors. Neurotransmitters
appear to be involved, especially dopamine and serotonin, but the processes by
which they influence sexual dysfunction are not clear.
PMID- 9637024
TI - Predictors of aggression in hospitalized adolescents.
AB - Client records spanning a 14-month period were examined for an adolescent unit of
a large state psychiatric hospital to identify client variables predictive of
acts of physical aggression in hospitalized adolescents. Forty-two percent of the
43 girls and 55% of the 57 boys were classified as aggressive because they had
committed at least one act of physical aggression during the data collection
period. In logistic regression analyses, client characteristics were used to
predict aggression classification and 79%, 81%, and 92% of the total sample,
girls, and boys, respectively, were correctly classified. Aggression in the girls
was associated with having a history of family violence, being of a minority
race, and being on medication; for the boys, aggression was associated with a
diagnosis of a conduct disorder, being on medication, and being previously
hospitalized.
PMID- 9637025
TI - Physiological studies of the precedence effect in the inferior colliculus of the
kitten.
AB - The precedence effect (PE) is a perceptual phenomenon that reflects listeners'
ability to suppress echoes in reverberant environments. The PE is not present at
birth and appears only several months postnatal. Recent physiological studies
have demonstrated correlates of the PE in the central nucleus of the inferior
colliculus (ICC) of adult animals. The present study extended the same techniques
to search for similar correlates in the ICC of kittens during the first postnatal
month. Stimuli consisted of pairs of clicks or noise bursts presented from
different locations in free field or with different inter-aural differences in
time (ITD) under headphones, with an inter-stimulus-delay (ISD) between their
onsets. Results suggest that a physiological correlate of the PE, i.e.
suppression of responses to the second source, is present as early as 8 days
postnatal, and occurs at similar ISDs to those recorded in adult cats.
Suppression in kitten neurons varies with stimulus level, duration, and azimuthal
position, in a similar manner to that in adult neurons. The age at which
correlates of the PE in the kitten can be found precedes the age at which kittens
can localize sound sources effectively, and presumably before the age at which
they would demonstrate the PE behaviorally. Thus, the neural mechanisms that
might be involved in the first stages of processing PE stimuli may be in place
well before the behavioral correlate develops.
PMID- 9637026
TI - Voice F0 responses to manipulations in pitch feedback.
AB - Recent studies have shown that when phonating subjects hear their voice pitch
feedback shift upward or downward, they respond with a change in voice
fundamental frequency (F0) output. Three experiments were performed to improve
our understanding of this response and to explore the effects of different
stimulus variables on voice F0 responses to pitch-shift stimuli. In experiment 1,
it was found that neither the absolute level of feedback intensity nor the
presence of pink masking noise significantly affect magnitude or latency of the
voice F0 response. In experiment 2, changes in stimulus magnitude led to no
systematic differences in response magnitudes or latencies. However, as stimulus
magnitude was increased from 25 to 300 cents, the proportion of responses that
changed in the direction opposite that of the stimulus ("opposing" response)
decreased. A corresponding increase was observed in the proportion of same
direction responses ("following" response). In experiment 3, increases in pitch
shift stimulus durations from 20 to 100 ms led to no differences in the F0
response. Durations between 100 and 500 ms led to longer duration voice F0
responses with greater response magnitude, and suggested the existence of a
second F0 response with a longer latency than the first.
PMID- 9637027
TI - Measurements of differential scattering cross section using a ring transducer.
AB - A procedure for the measurement of intrinsic scattering object properties is
presented and used to obtain illustrative results. The procedure is based on the
measurement of the scattered acoustic field as a function of scattering angle and
frequency. Measurements are normalized using analytically determined expressions
for emitter and detector beams resulting from a combination of unfocused linear
elements arranged in a circular configuration. The spatial effects of finite
emitter pulse length and detector gate length are represented by a convolution
formula valid for narrow-band transmitted signals and long receiver gates. The
normalization includes correction for target absorption as well as measurement of
the directly transmitted acoustic power in the free field and yields the average
differential scattering cross section per unit volume. Under the Born
approximation, this quantity is directly proportional to the spatial-frequency
spectrum of the scattering medium inhomogeneities. Measured results are reported
for two phantoms consisting of glass microspheres embedded in a weakly absorbing
agar background medium. For the phantoms employed, scattering effects, rather
than increased absorption, are shown to account for most of the difference in
transmission loss between pure agar and agar with glass spheres. The measured
differential scattering cross sections are compared with theoretical cross
sections for distributions of glass spheres measured experimentally. The measured
values show good relative agreement with theory for varying angle, frequency, and
phantom properties. The results are interpreted in terms of wave space resolution
and the potential for tissue characterization using similar fixed transducer
configurations.
PMID- 9637028
TI - Predicting hearing aid response in real ears.
AB - A hearing aid fitted to different ears will produce very different sound pressure
spectra in the ear canal. In addition, this variation in response is different
among hearing aids. A description in terms of an electrical analog model of the
ear and hearing aid system is given. The applicability of this model is tested
through series of measurements. The measurement and prediction procedure was
first verified on a coupler (ear simulator) with good results from 300 to 8000
Hz. Three types of hearing aids were then measured and used on five different
human ears. Where the measured and predicted response was compared a fairly good
agreement was obtained from 300 Hz to approximately 6000 Hz. A major source of
error is probe misalignment. The theoretical description given in the present
work is likely to be valid from low frequencies to at least 10 kHz. Although
solutions for related problems have been given for low frequencies, a solution of
the hearing aid fitting problem at high frequencies has not been published
earlier.
PMID- 9637029
TI - Growth behavior of the 2 f1-f2 distortion product otoacoustic emission in
tinnitus.
AB - High-resolution hearing threshold and 2 f1-f2 distortion product otoacoustic
emission (DP) were measured with the same in-the-ear sound probe and same
calibration at 51 frequencies between 500 and 8000 Hz in 39 sensorineural hearing
loss ears associated with tinnitus. Using a primary tone setting L1 = 0.4L2 + 39
that accounts for the nonlinear interaction of the two primary tones at the DP
generation site at f2, DPs were elicited in a wide range from L2 = 65 to 20 dB
SPL. We failed to find a uniform DP behavior in the 39 tinnitus ears tested.
Seventeen of them behaved like impaired ears without tinnitus. In these ears a
linearized DP growth was observed where the DP level decreased and the slope of
the DP I/O functions steepened with increasing hearing loss and as a result both
the DP level and the DP slope strongly correlated with hearing threshold. The
other population, 22 tinnitus ears, exhibited a poor or even inverse relationship
between DP level and hearing threshold, i.e., displayed an increase of DP level
with increasing hearing loss. Despite the severe hearing loss but due to the high
level, DPs could be recorded well in the frequency range that corresponded to the
appearance of the tinnitus. The DP slope, however, increased with increasing
hearing loss and, therefore, did still correlate with hearing threshold revealing
pathological alteration. The data suggest that the DP level alone is hardly
capable of assessing hearing impairment in tinnitus ears and may even be
misleading. Thus just the DP slope seems to be the only reliable indicator of
cochlear malfunction around the tinnitus frequency. The observed nonuniform DP
behavior suggests different cochlear impairments in tinnitus ears. In those ears
where the DP level decreases and the slope of the I/O functions increases with
hearing loss, cochlear sensitivity and tuning are supposed to be diminished. In
those ears where the DP level increases with increasing hearing loss, a
reinforced mechanical distortion is hypothetized to be generated by cochlear
hyperactivity that can be the source of both the abnormally high DP level and the
tinnitus.
PMID- 9637030
TI - The level and growth behavior of the 2 f1-f2 distortion product otoacoustic
emission and its relationship to auditory sensitivity in normal hearing and
cochlear hearing loss.
AB - The 2 f1-f2 distortion product otoacoustic emission (DP) was measured in 20
normal hearing subjects and 15 patients with moderate cochlear hearing loss and
compared to the pure-tone hearing threshold, measured with the same probe system
at the f2 frequencies. DPs were elicited over a wide primary tone level range
between L2 = 20 and 65 dB SPL. With decreasing L2, the L1-L2 primary tone level
difference was continuously increased according to L1 = 0.4L2 + 39 dB, to account
for differences of the primary tone responses at the f2 place. Above 1.5 kHz, DPs
were measurable with that paradigm on average within 10 dB of the average hearing
threshold in both subject groups. The growth of the DP was compressive in normal
hearing subjects, with strong saturation at moderate primary tone levels. In
cases of cochlear impairment, reductions of the DP level were greatest at lowest,
but smallest at highest stimulus levels, such that the growth of the DP became
linearized. The correlation of the DP level to the hearing threshold was found to
depend on the stimulus level. Maximal correlations were found in impaired ears at
moderate primary tone levels around L2 = 45 dB SPL, but at lowest stimulus levels
in normal hearing (L2 = 25 dB SPL). At these levels, 17/20 impaired ears and
14/15 normally hearing ears showed statistically significant correlations. It is
concluded that for a clinical application and prediction of the hearing
threshold, DPs should be measured not only at high, but also at lower primary
tone levels.
PMID- 9637031
TI - Observing middle and inner ear mechanics with novel intracochlear pressure
sensors.
AB - Intracochlear pressure was measured in vivo in the base of the gerbil cochlea.
The measurements were made over a wide range of frequencies simultaneously in
scalae vestibuli and tympani. Pressure was measured just adjacent to the stapes
in scala vestibuli and at a number of positions spaced by tens of micrometers,
including a position within several micrometers of the basilar membrane, in scala
tympani. Two findings emerged from the basic results. First, the spatial
variation in scala tympani pressure indicated that the pressure is composed of
two modes, which can be identified with fast and slow waves. Second, at
frequencies between 2 and 46 kHz (the upper frequency limit of the measurements)
the scala vestibuli pressure adjacent to the stapes had a gain of approximately
30 dB with respect to the pressure in the ear canal, and a phase which decreased
linearly with frequency. Thus, over these frequencies the middle ear and its
termination in the cochlea operate as a frequency independent transmission line.
A subset of the data was analyzed further to derive the velocity of the basilar
membrane, the pressure difference across the organ of Corti complex (defined to
include the tectorial and basilar membranes) and the specific acoustic impedance
of the organ of Corti complex. The impedance was found to be tuned in frequency.
PMID- 9637032
TI - Paradoxical relationship between frequency selectivity and threshold sensitivity
during auditory-nerve fiber development.
AB - The acquisition of adult-like frequency selectivity is generally assumed to be
the tightly coupled to improvements in threshold sensitivity during cochlear
development. In this study, frequency versus threshold (tuning) curves obtained
from 1108 auditory-nerve fibers were used to investigate the relationship between
tuning and threshold at characteristic frequency (CF) during postnatal
development in kittens. At the earliest ages included in this study, sharpness
was within the adult range, but thresholds were significantly higher than adult
values. Tuning and thresholds improved along different exponential time courses
that varied with CF. For units with CFs below 1 kHz, tuning curve slopes below CF
matured earliest, followed by CF threshold, and then by slopes above CF. In
contrast, for CFs above 1 kHz, the high-frequency slopes matured first, followed
by threshold and then by slope below CF. One interpretation of these results is
that tuning and thresholds are not tightly coupled in immature animals.
Paradoxically, however, high-frequency slopes were correlated with threshold for
individual units at all ages, suggesting that the relationship between tuning and
threshold is maintained during development. This contradiction can be resolved by
a developmental model that features a functional separation between cochlear
nonlinearities and mechanical/electrical conversion.
PMID- 9637033
TI - Interrupted noise exposures: threshold shift dynamics and permanent effects.
AB - A parametric study of the reduction of threshold shift (toughening phenomena)
that takes place during the course of an interrupted noise exposure is described.
266 chinchillas randomly assigned to one of 32 experimental groups were exposed
to one of the following: a 400-Hz narrow-band impact noise having a center
frequency of 0.5, 1.0, 2.0, 4.0, or 8.0 kHz and peak sound-pressure levels of
109, 115, 121, or 127 dB. The impacts were presented for 5 d, 24 h/d or for 20 d,
6 h/d. corresponding pairs of exposures had equal energy. Group mean noise
effects were estimated from pure-tone threshold obtained form inferior colliculus
evoked potentials and from surface preparation histology. The threshold shift
(TS) toughening phenomena is shown to occur in response to all stimuli that
produce a TS and at all audiometric test frequencies. The amount of toughening,
which is limited to less than 35 dB, varies with noise frequency and intensity.
Based on group mean data the auditory system is not protected from the permanent
effects of an interrupted noise exposure as a result of the toughening effect but
rather differences in permanent effects between the 5- and 20-d exposures are
attributed to the spreading of the exposure energy over an extended period of
time.
PMID- 9637034
TI - Double-evoked otoacoustic emissions. II. Intermittent noise rejection,
calibration and ear-canal measurements.
AB - Measurements of double-click-evoked otoacoustics emissions (2CEOAEs) and double
chirp distortion products (2ChDPs) are reported for normal-hearing adults based
upon theory presented in an earlier report [Keefe, J. Acoust, Soc. Am. 103, 3489
3498 (1998)]. The nonlinear acoustic response of a probe assembly used in ear
canal measurements in tested in a calibration cavity to compare the double-evoked
(2E) technique with existing OAE techniques. The 2E technique reduces the peak
distortion by approximately 30 dB relative to existing click-evoked techniques.
The 2E subtraction of click responses is partially analogous to current
techniques in that the linear response is eliminated, but differs in that high
frequency measurements are improved by eliminating time gating of the cochlear
response, and low-frequency measurements are improved by reducing probe
distortion, especially when two acoustic sources are used. Because time gating is
eliminated, it is straightforward to measure the onset of a click-evoked OAE. The
nonlinear coherence function is used to measure the nonlinear distortion signal
to-noise ratio (DNR) for the 2ChDPs and 2CEOAEs. The DNR is typically 20-30 dB.
An intermittent noise rejection technique is implemented in real time that
compares a currently acquired ear-canal response with a stored response.
Dissimilar responses indicate the presence of intermittent noise, and the noise
contaminated responses are thereby discarded before ensemble averaging.
PMID- 9637035
TI - Dichotic pitches as illusions of binaural unmasking. I. Huggins' pitch and the
"binaural edge pitch".
AB - The two most salient dichotic pitches, the Huggins pitch (HP) and the binaural
edge pitch (BEP), are produced by applying interaural phase transitions of 360
and 180 degrees, respectively, to a broadband noise. This paper examines accounts
of these pitches, concentrating on a "central activity pattern" (CAP) model and a
"modified equalization-cancellation" (mE-C) model. The CAP model proposes that a
dichotic pitch is heard at frequency f when an individual across-frequency scan
in an interaural cross-correlation matrix contains a sharp peak at f. The mE-C
model proposes that a dichotic pitch is heard when a plot of interaural
decorrelation against frequency contains a peak at f. The predictions of the
models diverge for the BEP at very narrow transition bandwidths: the mE-C model
predicts that salience is sustained, while the CAP model predicts that salience
declines and that the dominant percept is of the in-phase segment of the noise.
Experiment 1 showed that the salience of the BEP was sustained at the narrowest
bandwidths that could be generated (0.5% of the transition frequency). Experiment
2 confirmed that the pitch of a BEP produced by a 0.5% transition bandwidth was
close to the frequency of the transition band. Experiment 3 showed that pairs of
simultaneous narrow 180-degree transitions, whose frequencies corresponded to
vowel formants, were perceived as the intended vowels. Moreover, the same vowels
were perceived whether the in-phase portion of the noise lay between the two
transition frequencies or on either side of them. In contrast, different patterns
of identification responses were made to diotic band-pass and band-stop noises
whose cutoff frequencies corresponded to the same formants. Thus, the vowel
identification responses made to the dichotic stimuli were not based on hearing
the in-phase portions of the noise as formants. These results are not predicted
by the CAP model but are consistent with the mE-C model. It is argued that the mE
C model provides a more coherent and parsimonious account of many aspects of the
HP and the BEP than do alternative models.
PMID- 9637036
TI - Dichotic pitches as illusions of binaural unmasking. II. The Fourcin pitch and
the dichotic repetition pitch.
AB - The predictions of three models are compared with respect to existing
experimental data on the perception of the Fourcin pitch (FP) and the dichotic
repetition pitch (DRP). Each model generates a central spectrum (CS), which is
examined for peaks at frequencies consistent with the perceived pitches. A
modified equalization-cancellation (mE-C) model of binaural unmasking [Culling
and Summerfield, J. Acoust. Soc. Am. 98, 785-797 (1995)] generates a CS which
reflects the degree of interaural decorrelation present in each frequency
channel. This model accounts for the perceived frequencies of FPs, but produces
no output for DRP stimuli. A restricted equalization-cancellation (rE-C) model
[Bilsen and Goldstein, J. Acoust. Soc. Am. 55, 292-296 (1974)] sums the time
varying excitation in corresponding frequency channels, without equalization, to
form a CS. A central activity pattern (CAP) model [Raatgever and Bilsen, J.
Acoust. Soc. Am. 80, 429-441 (1986)] generates a CS by scanning an interaural
cross-correlation matrix across frequency. The rE-C and CAP models yield
inaccurate predictions of the perceived frequencies of FPs, but predict the
occurrence of the DRP and its correct pitch. The complementary predictions of the
mE-C model compared to the rE-C and CAP models, together with the evidence that
the FP is clearly audible for the majority of listeners, while the DRP is faintly
heard by a minority of listeners, suggest that the mE-C model provides the best
available account of the FP, and that the DRP is produced by a separate
mechanism.
PMID- 9637037
TI - Evidence for an across-frequency, between-channel process in asymptotic monaural
temporal gap detection.
AB - Monaurally measured temporal gap detection (TGD) thresholds characteristically
increase as the frequency difference is increased over a range of about half an
octave to an octave between two sinusoids that mark the onset and offset of the
silent gap. For greater sinusoidal frequency separations, the TGD thresholds
often become asymptotic. This pattern probably reflects two different processes.
The first process likely reflects within-channel processing within a single
auditory filter or channel. The second process is less certain, but may reflect
between-channel processing of the silent gap stimulus across two or more
independent frequency channels. To evaluate the hypothesis that asymptotic
monaural gap detection can be explained by a simple between-channel process, TGD
thresholds were measured as a function of frequency separation between a pregap
sinusoid presented to the left ear (channel 1) and a postgap sinusoid, of higher
frequency, presented to the right ear (channel 2). The rationale for dichotic
presentation of the sinusoidal markers and gap signal followed from the fact that
the gap detection task must be performed between two independent channels by
combining the outputs from each channel (ear) and recovering the gap information
centrally. The resulting TGD thresholds for pregap sinusoids from 250 to 4000 Hz
were relatively invariant and increased only slightly with increasing marker
frequency separation. The average TGD thresholds for four listeners were in the
range of 30 to 40 ms, which corresponded closely with their asymptotic TGD
thresholds for the same set of stimulus conditions measured monaurally. This
correspondence of the two data sets supports an across-frequency, between-channel
process for asymptotic monaural gap detection at marker frequency separations
greater than about half an octave.
PMID- 9637038
TI - The role of auditory filters in comodulation masking release (CMR).
AB - Comodulation masking release (CMR) is the detection advantage conferred by
coherence of amplitude modulation across masker frequency. This phenomenon has
typically been described in terms of across-frequency comparisons or in terms of
cueing, where analysis of the output of an auditory filter in the region of the
signal is aided by the outputs of independent auditory filters. An alternative
approach is to assume a broad initial predetection filter, one which encompasses
frequencies generally thought to fall into disparate auditory filters. These two
basic approaches are compared. Stimuli consisted of comodulated maskers, spaced
in frequency at one of three fixed intervals, with fine structure that either
produced strong envelope beats in the summed waveform or did not. The signal was
a pure tone of random starting phase. For the smallest masker frequency spacing
detection of a high-frequency signal seemed to be improved in the presence of
envelope beats, while detection of a low-frequency signal seemed to be degraded
by envelope beats. These results are discussed in terms of the number of maskers
assumed to sum in an auditory filter and the relative availability of within- and
between-channel cues. This explanation is consistent with an initial stage of
auditory filtering and is fundamentally inconsistent with a broad initial filter.
Results for larger masker frequency spacings showed this trend less reliably, a
finding that was further explored via data from a modulation discrimination task.
PMID- 9637039
TI - Auditory perception following hair cell regeneration in European starling
(Sturnus vulgaris): frequency and temporal resolution.
AB - Behavioral detection thresholds, auditory filter widths, and temporal modulation
transfer functions were obtained from four starlings before, during and after 11
days of subcutaneous injections of kanamycin, an aminoglycoside antibiotic. Birds
were operantly conditioned to respond to pure tones and amplitude modulated
noises ranging in frequency from 0.25 to 7 kHz using adaptive staircase
procedures and were tested daily for 92 days after the first injection of
aminoglycoside. All birds had threshold shifts of at least -60 dB at frequencies
above 4 kHz. Lower frequencies were affected in some birds, although none of the
birds had hearing loss below 3 kHz. All four birds had wider auditory filters at
5 kHz immediately after the aminoglycoside series. Any changes in frequency
resolution at frequencies below 5 kHz were slight, transitory, and rarely
observed. Two of the four birds had permanently wider auditory filters at 5 kHz.
Temporal modulation transfer functions were briefly affected in two birds during
the time of greatest threshold shift. Recovery of detection thresholds began soon
after the injections ceased and continued for approximately 60 days. Recovery in
frequency resolution lagged behind auditory threshold by about 10 days. Normal
temporal resolution was observed in the context of impaired intensity and
frequency resolution. Changes in auditory threshold and frequency resolution were
closely associated for all birds at 5 kHz, but were correlated with statistical
significance in only two birds. Scanning electron microscopy was performed on all
four birds after 90 days of recovery and confirmed that the extent of initial
damage was consistent with the pattern of observed hearing loss.
PMID- 9637040
TI - Auditory scene analysis by European starlings (Sturnus vulgaris): perceptual
segregation of tone sequences.
AB - Like humans, animals that use acoustic stimuli to perceive their world ought to
be able to parse the auditory scene into functionally significant sounds. The
ability to do so ought to have significant adaptive value when, for example, an
animal can identify the sounds of a predator among other natural noises. In
earlier work it was shown that a species of songbird, the European starling, can
identify excerpts of both its own song and songs from other avian species when
the songs are mixed concurrently with other natural signals. In this experiment
it is demonstrated that starlings can segregate two synthetic pure-tone sequences
when the sequences differ in frequency. Taken together, the experiments show that
at least one nonhuman species is capable of auditory scene analysis both for
natural and for non-natural acoustic stimuli. This suggests in turn that auditory
scene analysis may be a general perceptual process that occurs in many species
that make use of acoustic information.
PMID- 9637041
TI - Effects of spectral pattern on the perceptual salience of partials in harmonic
and frequency-shifted complex tones: a performance measure.
AB - A single even harmonic added to an odd-harmonic complex is often judged to be
more salient than its odd neighbors in a clarity rating task [Roberts and
Bregman, J. Acoust. Soc. Am. 90, 3050-3060 (1991)]. This study used similar
complexes in a two-interval forced-choice procedure. Each interval consisted of a
complex tone followed by a pure tone, whose frequency matched that of a harmonic
in one interval but was changed by +/- 0.5 x fundamental frequency in the other.
Subjects were asked to identify the matching interval. Since the pure tone
followed the complex tone, it could not cue listening to a particular frequency
region. The possibility of cross-interval cuing was reduced by changing the
fundamental frequency between intervals (100-150 Hz range). The procedure was
designed to maximize the effects on performance of differences in immediate
perceptual salience between the partials. The added even harmonic was typically
judged with greater accuracy than its odd neighbors (experiment 1), though this
effect was greatly reduced for harmonics above 8 (experiment 2). The even-odd
difference persisted when the original stimuli were made inharmonic by applying a
frequency shift of 15%, but was abolished for stimuli consisting of successive
partials (experiment 3).
PMID- 9637042
TI - Adaptation in the processing of interaural time differences revealed by the
auditory localization aftereffect.
AB - Two experiments were conducted involving the auditory localization aftereffect,
in which the perceptual lateralization of a test sound having an interaural time
difference (ITD) shifts away from that of a prior adapting sound having a
different ITD. First, the frequency selectivity of the aftereffect was examined
for sinusoids presented through headphones, with various combinations of adapter
and test frequencies below 800 Hz, using the method of constant stimuli. The
magnitude of the aftereffect was found to be largest when the frequencies of the
two tones were similar, and virtually disappeared at a frequency difference of
one-half octave. Second, the ITD selectivity of the aftereffect was examined for
400-Hz sinusoids. Subjects' judgments of lateralization were measured directly in
terms of the perceived azimuth of the test tone for various combinations of
adapter and test ITDs in the range of +/- 625 microseconds. The magnitude of the
aftereffect was found to be largest when adapter and test ITDs differed by
approximately 250 microseconds. These results were successfully simulated by an
interaural cross-correlation model having gain control. The results are
consistent with the idea that the gain of ITD-selective units, located after
binaural interaction but before across-frequency integration, is changed by
recent input.
PMID- 9637043
TI - An adaptive noise canceller for hearing aids using two nearby microphones.
AB - An adaptive noise cancellation scheme based on two-stage adaptive filtering as
proposed by Van Compernolle [Proceedings of the IEEE International Conference on
Acoustics, Speech and Signal Processing (IEEE, New York, 1990)] was tested for
two identical directional microphones mounted in an endfire configuration within
a single behind-the-ear (BTE) hearing aid. Speech intelligibility tests were
carried out with two normal hearing subjects and three hearing aid users with
moderate hearing losses, in a realistic test environment using open set words and
sentences. A significant improvement, on average more than 5 dB, of speech
reception threshold (SRT) in background noise was obtained.
PMID- 9637044
TI - Deformation analysis of the vocal folds from videostroboscopic image sequences of
the larynx.
AB - Videostroboscopy is an examination which yields a permanent record of the moving
vocal folds. Thus, it allows the diagnosis of abnormalities which contribute to
voice disorders. In this paper, in order to find and quantify the deformation of
the vocal folds in videostroboscopic recordings, an active contours- (snakes)
based approach is used to delineate the vocal folds in each frame of the
videostroboscopic image sequence. After this delineation, a new elastic
registration algorithm is used to register the vocal fold contours between
adjacent frames of the video sequence. This algorithm is based on the
regularization principle and is very effective when large deformations are
present. A least-squares approach is used to fit an affine model to the
displacement vectors found by elastic registration. The parameters of this model,
rotation, translation, and deformation along two principle axes, quantify the
deformation and allow the succinct characterization of the videostroboscopic
recordings based on the deformations that occurred. Experiments are shown with
synthetic and real videostroboscopic data that demonstrate the value of the
proposed approach.
PMID- 9637045
TI - Fundamental frequency during phonetically governed devoicing in normal young and
aged speakers.
AB - Age-related changes in the laryngeal system can be perceived as altered vocal
pitch and increased pitch variability. However, reports vary as to the nature and
extent of an age effect on fundamental frequency (F0) for analyses taken over
long segments of connected speech. Analysis of F0 across a smaller time frame may
be more informative. Young speakers show an increase in F0 associated with
phonetically governed devoicing gestures that is likely mediated by increased
vocal fold stiffness. Anatomic and neurophysiologic changes in the aged larynx
may limit the role of increased vocal fold stiffness in the devoicing gesture.
This study tests the hypothesis that aged speakers show a smaller increase in F0
in association with the devoicing gesture for production of an intervocalic
voiceless obstruent than do young speakers. Normal young and aged speakers
produced a short sentence containing an intervocalic voiceless obstruent.
Measures of F0 were obtained for ten cycles before voice offset and ten cycles
after voice onset. Young speakers showed a small increase in F0 during devoicing
whereas aged speakers showed a decrease in F0 during devoicing. Aged speakers
seem to rely more on vocal fold abduction rather than a combination of abduction
and tensing to achieve devoicing.
PMID- 9637046
TI - Depolarizing the perceptual magnet effect.
AB - In recent years there has been a great deal of interest in demonstrations of the
so-called "Perceptual-Magnet Effect" (PME). In these studies, AX-discrimination
tasks purportedly reveal that discriminability of speech sounds from a single
category varies with judged phonetic "goodness" of the sounds. However, one
possible confound is that category membership is determined by identification of
sounds in isolation, whereas, discrimination tasks include pairs of stimuli. In
the first experiment of the current study, identification and goodness judgments
were obtained for vowels (/i/-/e/) presented in pairs. A substantial shift in
phonetic identity was evidenced with changes in the context vowel. In a second
experiment, listeners participated in an AX-discrimination task with the vowel
pairs from the first experiment. Using the contextual identification functions
from the first experiment, predictions of discriminability were calculated using
the classic tenets of Categorical Perception. Obtained discriminability functions
were well accounted for by predictions from identification. There was no
additional unexplained variance that required the proposal of "perceptual
magnets." These results suggest that PME may be nothing more than further
demonstration that general discriminability is greater for cross-category
stimulus pairs than for within-category pairs.
PMID- 9637047
TI - Adapting to supernormal auditory localization cues. I. Bias and resolution.
AB - Head-related transfer functions (HRTFs) were used to create spatialized stimuli
for presentation through earphones. Subjects performed forced-choice,
identification tests during which allowed response directions were indicated
visually. In each experimental session, subjects were first presented with
auditory stimuli in which the stimulus HRTFs corresponded to the allowed response
directions. The correspondence between the HRTFs used to generate the stimuli and
the directions was then changed so that response directions no longer
corresponded to the HRTFs in the natural way. Feedback was used to train subjects
as to which spatial cues corresponded to which of the allowed responses. Finally,
the normal correspondence between direction and HRTFs was reinstated. This basic
experimental paradigm was used to explore the effects of the type of feedback
provided, the complexity of the stimulated acoustic scene, the number of allowed
response positions, and the magnitude of the HRTF transformation subjects had to
learn. Data showed that (1) although subjects may not adapt completely to a new
relationship between physical stimuli and direction, response bias decreases
substantially with training, and (2) the ability to resolve different HRTFs
depends both on the stimuli presented and on the state of adaptation of the
subject.
PMID- 9637048
TI - Adapting to supernormal auditory localization cues. II. Constraints on adaptation
of mean response.
AB - A series of experiments was performed in which subjects were trained to interpret
auditory localization cues arising from locations different from their normal
spatial positions. The exact pattern of mean response to these alterations (as a
function of time) was examined in order to begin to develop a quantitative model
of adaptation. Mean responses were roughly proportional to the normal position
associated with the localization cues presented. As subjects adapted, the best
fit slope (relating mean response and normal position) changed roughly
exponentially with time. The exponential rate and adaptation asymptote were found
for each subject in each experiment, as well as the rate and asymptote of
readaptation to normal cues. The rate of adaptation does not show any statistical
dependence on experimental conditions; however, the asymptote of the best-fit
slope varied with the strength of the transformation used in each experiment.
This result is consistent with the hypothesis that subjects cannot adapt to a
nonlinear transformation of auditory localization cues, but instead adapt to a
linear approximation of the transformation. Over time, performance changes
exponentially towards the best-fit linear approximation for the transformation
used in a particular experiment, and the rate of this adaptation does not depend
upon the transformation employed.
PMID- 9637049
TI - Complementarity and synergy in bimodal speech: auditory, visual, and audio-visual
identification of French oral vowels in noise.
AB - The efficacy of audio-visual interactions in speech perception comes from two
kinds of factors. First, at the information level, there is some
"complementarity" of audition and vision: It seems that some speech features,
mainly concerned with manner of articulation, are best transmitted by the audio
channel, while some other features, mostly describing place of articulation, are
best transmitted by the video channel. Second, at the information processing
level, there is some "synergy" between audition and vision: The audio-visual
global identification scores in a number of different tasks involving acoustic
noise are generally greater than both the auditory-alone and the visual-alone
scores. However, these two properties have been generally demonstrated until now
in rather global terms. In the present work, audio-visual interactions at the
feature level are studied for French oral vowels which contrast three series,
namely front unrounded, front rounded, and back rounded vowels. A set of
experiments on the auditory, visual, and audio-visual identification of vowels
embedded in various amounts of noise demonstrate that complementarity and synergy
in bimodal speech appear to hold for a bundle of individual phonetic features
describing place contrasts in oral vowels. At the information level
(complementarity), in the audio channel the height feature is the most robust,
backness the second most robust one, and rounding the least, while in the video
channel rounding is better than height, and backness is almost invisible. At the
information processing (synergy) level, transmitted information scores show that
all individual features are better transmitted with the ear and the eye together
than with each sensor individually.
PMID- 9637050
TI - Sinuous instability of a planar air jet: propagation parameters and acoustic
excitation.
AB - The sinuous instability wave of a planar air jet is excited by localized acoustic
flow across the nozzle. Phase velocity and the growth exponent are found from
synchronous hot-wire measurements made beyond the excited region, where the
profile is approximately sech-squared. In the observed range of scaled radian
frequency, 0.02-1.33 (the stability limit), results agree with real-frequency
(spatially growing) analysis but not with complex-frequency (temporally growing)
analysis. The latter predicts smaller phase velocity at low frequencies and has
been questioned in edgetone analysis. In further tests, the acoustic driving
signal is made independent of downstream distance, as in an organ pipe. The jet
deflection is then the sum of acoustic convection and of the instability wave,
summing to zero at the nozzle, as proposed by Fletcher, Elder, and others. The
instability-wave theory applies to linear behavior in the inviscid limit and
therefore to a hypothetical nonspreading jet. The local velocity profile width
must be considered in relating to a physical jet. In a flue organ pipe
oscillating at equilibrium amplitude the stability-wave theory is not applicable
near the lip, where the laminar flow assumed in the theory disappears and the jet
deflection exceeds the range of linear behavior. Direct sound generation by the
jet is investigated briefly.
PMID- 9637051
TI - Variables controlling contrast generation in a urinary bladder model.
AB - An ultrasound system has been developed to generate microbubbles in vivo for use
as ultrasound contrast agent. Possible application include diagnosis of reflux in
the urinary tract. In experiments designed to elucidate the contrast microbubble
generation process, acoustic bursts (at 1.8 MHz, 125 ms) were propagated through
a latex rubber balloon, modeled after a rabbit urinary bladder, containing fluids
of various air and carbon dioxide saturations and concentrations of cavitation
nuclei (0.198-micron-diam polystyrene particles). The peak rarefactional pressure
threshold for contrast microbubble generation, as visualized with a diagnostic
ultrasound system, decreased approximately a factor of 2 for increasing particle
concentration from 10(8) to 10(10) particles/cc, with the lowest threshold of
5.24 MPa. For samples with gas saturations below 50% and 10(10) particles/cc, the
average thresholds were at least twice as high as those of more saturated fluids
(with mean threshold for saturated fluids of 6.45 MPa), and samples containing
CO2 had considerably lower thresholds than respective under-saturations in air.
At a fixed pressure amplitude, echogenicity tended to increase with both
increasing particle concentration and gas saturation; this was more favorable for
samples containing CO2. Even in a restricted-nuclei environment such as the
urinary bladder, generation of vaporous cavitation should be possible; however,
subsequently, abundant gas is needed to grow vaporous bubbles to persistent and
imageable sizes, to assist in the diagnosis of urinary reflux.
PMID- 9637052
TI - A method for forward and inverse solutions of a three-dimensional model of the
cochlea.
PMID- 9637053
TI - Auditory saltation: a new measure for an old illusion.
PMID- 9637054
TI - Effect of climate upon organ tone.
PMID- 9637055
TI - Evolution of segregation distortion: potential for a high degree of polymorphism.
AB - By means of a population genetical model, we study the evolution of segregation
distortion. Most models of segregation distortion focus on a single distorter
allele. In contrast, we consider the competition between a large number of
distorters. Motivated by systems as the t complex of the house mouse or the Sd
complex of Drosophila melanogaster, we assume that there is some
"complementation" between distorter alleles, i.e. that the fitness of individuals
heterozygous for two distorter alleles is higher than the fitness of homozygous
individuals. In the presence of complementation, the most efficient distorter
allele with the highest segregation ratio often does not outcompete less
efficient distorters. In fact, our results show that coexistence of a large
number of distorter alleles is more typical than the competitive exclusion of
less efficient distorters by a single superior allele. We first consider the
analytically tractable system where all distorters show the same amount of
complementation. In this case, all distorters with a segregation ratio higher
than a certain critical value will persist, resulting in a polymorphic population
where the average segregation ratio is only slightly larger than 0.5. If the
degree of complementation varies, there may be more than one stable equilibrium,
and the outcome of competition may depend on the initial conditions. Motivated by
empirical examples, we also consider the case that the distorting ability of an
allele is negatively related to its effects on individual fitness. Interestingly,
the outcome of competition depends crucially on details of such a trade-off. We
conclude that verbal arguments are insufficient to predict the evolution of
segregation distortion.
PMID- 9637056
TI - Cyclical neutropenia and the peripheral control of white blood cell production.
AB - Cyclical neutropenia (CN) is an interesting dynamic hematological disease in
which the neutrophils spontaneously oscillate from approximately normal levels to
near zero with a period between 19 and 21 days. In the only known animal model
for this disorder, the grey collie, the disease's single apparent difference from
human CN is the smaller period of 11-15 days. CN can be treated using the
cytokine G-CSF which decreases the period (to about 14 days in humans), increases
the mean value, and elevates the amplitude of the oscillations. After reviewing
the clinical and laboratory data on this disease, we examine the proposition that
CN is due to a loss of stability in the peripheral negative feedback control of
neutrophil production. This is accomplished by the development of a
physiologically realist mathematical model for the system. We conclude that there
is no consistent way in which such a destabilization can give rise to either the
clinical or laboratory characteristics of CN. Rather it seems more likely that
the oscillations of CN are generated within the pluripotential stem cell
population.
PMID- 9637057
TI - Evaluation of residual stress in rabbit skin and the relevant material constants.
AB - Material constants are needed in order to evaluate stresses. The material
constants for orthotropic rabbit skin when residual stresses are eliminated, have
been evaluated by Tong & Fung [(1976). J. Biomechanics 9, 649-657]. It is well
documented that a circular skin sample taken from the human body becomes
elliptical in shape. Thus, it is clear that there are residual stresses in human
skin which need to be taken into consideration when evaluating the material
constants. In this paper, we therefore evaluate the material constants for rabbit
skin taking into account residual stresses.
PMID- 9637059
TI - A PRC based model of a pacemaker cell: effect of vagal activity and investigation
of the respiratory sinus arrhythmia.
AB - In this study we present a computer model of a pacemaker cell subjected to vagal
stimulation. This model allows us to investigate the entrainment phenomena of the
pacemaker cell resulting from its dynamic interaction with a periodic train of
vagal bursts. The possibility of entrainment depends mainly on the fact that a
vagal stimulation discharge can "correct" the pacemaker rhythm by an amount that
depends on its instantaneous relationship to the pacemaker cycle length. This
very simple model, is based on the two most important functional properties of
the cardiac pacemaker cells. The first property is the intrinsic pacemaker cycle
length, which is an "internal" parameter of the cell, describing the most basic
feature of a pacemaker cell. The second one is the phase response curve (PRC),
which is an "overall collective" function, containing all the "information" about
the possible interactions between the pacemaker cell and the outside world (i.e.
its interaction with surrounding cells, external stimulus, etc.). A "collective"
PRC was reconstructed from the resulting effects of all the pulses composing a
burst. It appears that the PRC parameters as well as the vagal burst parameters
are important factors in predicting the entrainment phenomena. Specifically, we
found that the tendency of the pacemaker cell to become synchronized with bursts
of vagal activity is greater, the larger the number of pulses per burst. However,
increasing the number of pulses may also increase the tendency of the pacemaker
towards instability, which was unveiled as changes in the configuration of the
"collective" PRC. We applied the periodic train of vagal bursts so as to simulate
the respiratory sinus arrhythmia (RSA) modulation on the pacemaker cell. We
included also a modulation of sympathetic origin, represented as periodic changes
in the intrinsic pacemaker cycle length. The frequency response of the pacemaker
to "autonomic" modulations allowed us to demonstrate that the RSA dynamics can be
interpreted in terms of the entrainment of the pacemaker cell by the respiratory
modulation of vagal activity.
PMID- 9637060
TI - Topographic mapping in the retinotectal projection by means of complementary
ligand and receptor gradients: a computer simulation study.
AB - Based on recent experimental studies of complementary gradients of receptor
density (R) on the retinal surface and ligand density (L) on the tectal surface,
and mapping of the high point on the receptor gradient to the low point on the
ligand and vice versa, the servomechanism model was constructed involving a
mechanism for the retinal axon to reach its target automatically sensing a
difference between the signal strength (R.L) and the standard value (S). Computer
simulations based on the model demonstrated desired two-dimensional topographic
mapping of the retinal axons on the tectum, and explained three strange behaviors
of the retinal axons that had been observed in stripe assays for retinal axons
using stripes composed of tectal membrane fragments: repulsive behaviors of the
retinal axons by the ligand substances, uncertainty of the nasal axons whether or
not they show regional selectivity between substances of anterior and posterior
tecta, and abrupt transition of growth of the axons originating at continuously
varied retinal positions on the stripes having graded ligand density. Finally we
suggested what is to be improved in stripe assays with the artificial gradient of
the tectal membrane fragments.
PMID- 9637061
TI - Pepsin inhibitor from roots of Anchusa strigosa.
AB - A pepsin inhibitor of undetermined exact chemical composition was isolated from
the aqueous extracts of the roots of Anchusa strigosa. The extract of 1 g dry
roots inhibited 9380 +/- 390 micrograms of pepsin. The main steps of the
isolation procedure consisted of extraction in boiling water, precipitation at pH
3 and washing the precipitate with ethanol, column chromatography on sephadex G
75, and finally ultrafiltration on UM10 membrane. The specific activity at the
last step was 44 units ml-1 solution which measured 1.0 at 287 nm (a one unit of
the inhibitor is that amount which inhibited 1 microgram of pepsin under the
conditions of the assay). The overall purification was 22-fold. The inhibitor did
not bind CM-cellulose, but it did bind DEAE-cellulose irreversibly. A pepsin
inhibitor complex was formed with a KI = 2 x 10(-8) M. The inhibitor inhibited
peptic milk-clotting activity at pH 5.3. A solution of the inhibitor exhibited
split-peak spectra with two maxima at 280 nm and 287 nm. The epsilon at 287 nm
was estimated at 9.4 x 10(5) l mol-1 cm-1 based on a M(r) value which was
estimated at 62,500.
PMID- 9637062
TI - Inhibition of O2-reducing activity of horseradish peroxidase by
diphenyleneiodonium.
AB - Plant cells respond to pathogen attach with a burst of H2O2 secretion. The
question whether this defense reaction is catalysed by a NAD(P)H oxidase similar
to the NADPH oxidase of phagocytic leukocytes in mammals or by an extracellular
peroxidase is presently a matter of controversial debate. The observation that
H2O2 production by plant cells can be inhibited by diphenyleneiodonium (DPI), a
potent inhibitor of the mammalian NADPH oxidase, has fostered the view that a
mammalian-type enzyme is responsible for the H2O2 production by plant cells. Here
we show that DPI inhibits the NADH-dependent H2O2 production by horseradish
peroxidase in the same concentration range as previously used for the inhibition
of putative NADPH oxidase activity in plants. The peroxidative activity normally
used for assaying peroxidase is not affected by DPI, indicating that the
inhibitor specifically interferes with a partial reaction that is exclusively
involved in the O2 reducing activity of the enzyme.
PMID- 9637063
TI - Multiple forms of polygalacturonase from banana fruits.
AB - Three multiple forms of polygalacturonase (PG) in ripe and two in unripe banana
(Musa acuminata) fruits were separated by DEAE-cellulose and further purified
using Sephadex G-150 chromatography. The multiple forms can be differentiated
from each other on the basis of their properties. PG1 and PG3 were identified as
endo-PG and PG2 as exo-PG on the basis of decrease in viscosity, increase in
reducing sugar and the reaction product. PG2 and PG3 increased with the ripening
of fruits. PG1, PG2 and PG3 exhibited optimum activity at pH 3.3, 3.7 and 4.3,
respectively. Complete loss of PG2 and PG1 activities occurred at 60 and 70
degrees, but PG3 retained 60 and 50% activity respectively. The three forms
showed a different response towards divalent metal ions. Ca2+ activated PG1
activity only. Teepol 0.1%, inhibited PG1 activity by 25%, but PG2 and PG3
activities were completely inhibited. CTAB, 0.1%, had no effect on PG1 and PG2
activities, but inhibited PG3 activity by 40%. 2-ME stimulated PG2 and PG3
activities but had no effect on PG1 activity. Gel filtration through Sephacryl
indicated M(r) of 23,200, 58,000 and 130,000, respectively, for PG1, PG2 and PG3.
The substrate saturation curve for PG1 and PG2 were Michaelian, while PG3 showed
biphasic curve. The Km values of PG1 and PG2 were 0.22% and 0.14%, respectively.
PMID- 9637064
TI - Anthocyanin production of Glehnia littoralis callus cultures.
AB - A stable callus line that produces anthocyanins was established from callus
derived from a petiole of a Glehnia littoralis seedling and subcultured in the
dark. The major anthocyanin which made up about 60% of the total anthocyanins was
determined as cyanidin 3-O-(6-O-(6-O-(E)-feruloyl-beta-D-glucopyranosyl) -2-O
beta-D-xylopyranosyl-beta-D-glucopyranoside) by chemical and spectroscopic
analyses. Anthocyanin contents in the cells cultured on B5 basal medium
containing NAA (1 mg l-1), kinetin (0.01 mg l-1) and 3% sucrose reached 14% (dry
wt basis) and the productivity has been sustained for 5 years.
PMID- 9637065
TI - Sasanquol, a 3,4-seco-triterpene alcohol from sasanqua oil, and its anti
inflammatory effect.
AB - A novel 3,4-seco-triterpene alcohol, named sasanquol, was isolated from the non
saponifiable lipid of sasanqua oil from the seeds of Camellia sasanqua. Its
structure was established to be 3,4-seco-D:B-friedobacchara-4,21-dien-3-ol by
spectroscopic methods. This is the first example of naturally occurring
triterpene with a D:B-friedobaccharane skeleton. The 50% inhibitory dose of this
compound against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear
inflammation (1 microgram per ear) in mice was 0.4 mg per ear.
PMID- 9637066
TI - Phenylpropanoids and flavonoid glycosides from Lysionotus pauciflorus.
AB - A new phenylpropanoid glycoside, alpha-(3,4-dihydroxyphenyl)ethyl-(2'-O-alpha-L
rhamno-pyranosyl- 3'-O-beta-D-apiofuranosyl-4'-O-E-caffeoyl)-beta-D-glucopyran
oside, verbascoside, and two new flavone glucosides, nevadensin 7-O-beta-D
glucoside and nevadensin 7-O-[alpha-L-rhamnosyl(1-->6)]-beta-D-glucoside, have
been isolated from the aerial parts of Lysionotus pauciflorus. The structures
have been elucidated on the basis of spectroscopic data and chemical correlation.
PMID- 9637067
TI - An isopavine alkaloid from Thalictrum minus.
AB - A new alkaloid, isothalisopavine, was isolated from Thalictrum minus and shown to
be 2,3,8-trimethoxy-7-hydroxyisopavine from spectral evidence. The known
thalisopavine, from T. dasycarpum, is 2,3,8-trimethoxy-9-hydroxyisopavine.
Isothalisopavine is the first of its class to be substituted unsymmetrically in
the two aromatic rings.
PMID- 9637068
TI - Three-dimensional analysis of the senescence program in rice (Oryza sativa L.)
coleoptiles. Investigations of tissues and cells by fluorescence microscopy.
AB - The coleoptile of rice (Oryza sativa L. cv. Nippon-bare) emerges from an imbibed
seed on day 2 after sowing. Then, it matures and senesces rapidly. For analysis
of the senescence pattern within individual coleoptiles, we monitored the
distribution of chlorophyll (Chl) in entire coleoptiles and in cross-sections of
coleoptiles by recording the autofluorescence of Chl. Degradation of Chl was
apparent at the tip of the margins of opened-out coleoptiles on day 4, when the
overall levels of soluble protein and Chl per coleoptile had reached maximum
values. Then, senescence proceeded from the tip to the base and from the inner
mesophyll cells towards the outer epidermis, excluding tissues along vascular
bundles. Further analysis of cellular senescence using samples embedded in
Technovit 7100 resin revealed that the senescence of each green mesophyll cell
followed an identical program, which consisted of the following steps: (i)
degradation of chloroplast DNA; (ii) condensation of the nucleus, decrease in the
size of chloroplasts, degradation of ribulose-1,5-bisphosphate
carboxylase/oxygenase and chloroplast inner membranes; (iii) disorganization of
the nucleus; (iv) complete loss of cellular components, distortion of the cell
wall. Although the timing of each step and the rate at which each step was
completed differed among cells of different locations within the coleoptile, this
sequence was observed in all mesophyll cells in the coleoptile.
PMID- 9637069
TI - The promoter of a gene encoding a polygalacturonase-inhibiting protein of
Phaseolus vulgaris L. is activated by wounding but not by elicitors or pathogen
infection.
AB - Polygalacturonase-inhibiting proteins (PGIPs), leucine-rich repeat (LRR) proteins
evolutionarily related to several plant resistance genes, bind to and regulate
the action of fungal endopolygalacturonases. In Phaseolus vulgaris L., PGIPs are
encoded by a gene family comprising at least five members. As a start for a
systematic analysis of the regulation of the pgip family, we have analysed the
ability of the promoter of the bean gene pgip-1 to direct expression of beta
glucuronidase (GUS) in transfected tobacco protoplasts, microbombarded bean and
tobacco leaves, and transgenic tobacco plants. In protoplasts, the pgip-1 gene
region from nucleotide (nt) -2004 to nt +27 directed a level of expression that
was as high as that directed by the cauliflower mosaic virus (CaMV) 35S promoter
and could not be further induced by elicitor treatment; alteration of the region
immediately following the TATAA sequence at nt -29 abolished expression. Upon
stable integration into tobacco plants of the pgip-1 promoter-GUS construct, as
well as of a -394 deletion, expression was detected for both constructs mainly in
the stigma and, to a lesser extent, in the anthers and in the conductive vascular
tissue. The promoter responded to wounding but not to oligogalacturonides, fungal
glucan, salicylic acid, cryptogein, or pathogen infection. This expression
pattern does not mirror that of the whole pgip gene family.
PMID- 9637070
TI - Uptake and translocation of phosphate by pho2 mutant and wild-type seedlings of
Arabidopsis thaliana.
AB - The pho2 mutant of Arabidopsis thaliana (L.) Heynh. accumulates excessive Pi
(inorganic phosphate) concentrations in shoots compared to wild-type plants (E.
Delhaize and P. Randall, 1995, Plant Physiol. 107: 207-213). In this study, a
series of experiments was conducted to compare the uptake and translocation of Pi
by pho2 with that of wild-type plants. The pho2 mutants had about a twofold
greater Pi uptake rate than wild-type plants under P-sufficient conditions and a
greater proportion of the Pi taken up accumulated in shoots of pho2. When shoots
were removed, the uptake rate by roots was found to be similar for both
genotypes, suggesting that the greater Pi uptake by the intact pho2 mutant is due
to a greater shoot sink for Pi. Although pho2 mutants could recycle 32Pi from
shoots to roots through phloem the proportion of 32Pi translocated to roots was
less than half of that found in wild-type plants. When transferred from P
sufficient to P-deficient solutions, Pi concentrations in pho2 roots had a
similar depletion rate to wild-type roots despite pho2 shoots having a fourfold
greater Pi concentration than wild-type shoots throughout the experiment. We
suggest that the pho2 phenotype could result from a partial defect in Pi
transport in the phloem between shoots and roots or from an inability of shoot
cells to regulate internal Pi concentrations.
PMID- 9637071
TI - The role of acyl carrier protein isoforms from Cuphea lanceolata seeds in the de
novo biosynthesis of medium-chain fatty acids.
AB - To investigate the role of acyl carrier protein (ACP) in determining the fate of
the acyl moieties linked to it in the course of de-novo fatty acid biosynthesis
in higher plants, we carried out in vitro experiments to reconstitute the fatty
acid synthase (FAS) reaction in extracts of spinach (Spinacia oleracea L.)
leaves, rape (Brassica napus L.) seeds and Cuphea lanceolata Ait. seeds. The
action of two major C. lanceolata ACP isoforms (ACP 1 and ACP 2) compared to ACP
from Escherichia coli was monitored by saponification of the corresponding FAS
products with subsequent analysis of the liberated fatty acids by high
performance liquid chromatography. In a second approach the preference of the
medium-chain acyl-ACP-specific thioesterase (EC 3.1.2.14) of C. lanceolata seeds
for the hydrolysis of acyl-ACPs prepared from the three ACP types was
investigated. Both ACP isoforms from C. lanceolata seeds supported the synthesis
of medium-chain fatty acids in a reconstituted FAS reaction of spinach leaf
extracts. Compared to the isoform ACP 1, ACP 2 was more effective in supporting
the synthesis of such fatty acids in the FAS reaction of rape seed extracts and
caused a higher accumulation of FAS products in all experiments. No preference of
the medium-chain thioesterase for one specific ACP isoform was observed. The
results indicate that the presence of ACP 2 is essential for the synthesis of
decanoic acid in C. lanceolata seeds, and its expression in the phase of
accumulation of high levels of this fatty acid provides an additional and highly
efficient cofactor for stimulating the FAS reaction.
PMID- 9637072
TI - Photoinhibitory damage is modulated by the rate of photosynthesis and by the
photosystem II light-harvesting chlorophyll antenna size.
AB - We investigated the effect of photosynthetic electron transport and of the
photosystem II (PSII) chlorophyll (Chl) antenna size on the rate of PSII
photoinhibitory damage. To modulate the rate of photosynthesis and the light
harvesting capacity in the unicellular chlorophyte Dunaliella salina Teod., we
varied the amount of inorganic carbon in the culture medium. Cells were grown
under high irradiance either with a limiting supply of inorganic carbon, provided
by an initial concentration of 25 mM NaHCO3, or with supplemental CO2 bubbled in
the form of 3% CO2 in air. The NaHCO3-grown cells displayed slow rates of
photosynthesis and had a small PSII light-harvesting Chl antenna size (60 Chl
molecules). The half-time of PSII photodamage was 40 min. When switched to
supplemental CO2 conditions, the rate of photodamage was retarded to a t1/2 = 70
min. Conversely, CO2-supplemented cells displayed faster rates of photosynthesis
and a larger PSII light-harvesting Chl antenna size (500 Chl molecules). They
also showed a rate of photodamage with t1/2 = 40 min. When depleted of CO2, the
rate of photodamage was accelerated (t1/2 = 20 min). These results indicate that
the in-vivo susceptibility to photodamage is modulated by the rate of forward
electron transport through PSII. Moreover, a large Chl antenna size enhances the
rate of light absorption and photodamage and, therefore, counters the mitigating
effect of forward electron transport. We propose that under steady-state
photosynthesis, the rate of light absorption (determined by incident light
intensity and PS Chl antenna size) and the rate of forward electron transport
(determined by CO2 availability) modulate the oxidation/reduction state of the
primary PSII acceptor QA, which in turn defines the low/high probability for
photodamage in the PSII reaction center.
PMID- 9637073
TI - Nectar-carbohydrate production and composition vary in relation to nectary
anatomy and location within individual flowers of several species of
Brassicaceae.
AB - Nectar-carbohydrate production and composition were investigated by high
performance liquid chromatography and enzymology in nine species from five tribes
of the Brassicaceae. In six species (Arabidopsis thaliana (L.) Heynh., Brassica
napus L., B. rapa L., Lobularia maritima (L.) Desv., Raphanus sativus L., Sinapis
arvensis L.) that produced nectar from both lateral nectaries (associated with
the short stamens) and median nectaries (outside the long stamens), on average
95% of the total nectar carbohydrate was collected from the lateral ones. Nectar
from these glands possessed a higher glucose/fructose ratio (usually 1.0-1.2)
than that from the median nectaries (0.2-0.9) within the same flower.
Comparatively little sucrose was detected in any nectar samples except from
Matthiola bicornus (Sibth. et Sm.) DC., which possessed lateral nectaries only
and produced a sucrose-dominant exudate. The anatomy of the nectarial tissue in
nectar-secreting flowers of six species, Hesperis matronalis L., L. maritima, M.
bicornus, R. sativus, S. arvensis, and Sisymbrium loeselii L., was studied by
light and scanning-electron microscopy. Phloem alone supplied the nectaries.
However, in accordance with their overall nectar-carbohydrate production, the
lateral glands received relatively rich quantities of phloem that penetrated far
into the glandular tissue, whereas median glands were supplied with phloem that
often barely innervated them. All nectarial tissue possessed modified stomata
(with the exception of the median glands of S. loeselii, which did not produce
nectar); further evidence was gathered to indicate that these structures do not
regulate nectar flow by guard-cell movements. The numbers of modified stomata per
gland showed no relation to nectar-carbohydrate production. Taken together, the
data on nectar biochemistry and nectary anatomy indicate the existence of two
distinct nectary types in those Brassicacean species that possess both lateral
and median nectaries, regardless of whether nectarial tissue is united around the
entire receptacle or not. It is proposed that the term "nectarium" be used to
represent collectively the multiple nectaries that can be found in individual
flowers.
PMID- 9637074
TI - Compliance strategies and regulatory effectiveness of performance-based
regulation of chemical accident risks.
AB - This paper investigates the role that performance-based regulations can play in
linking a firm's environmental, health, and safety concerns with their corporate
strategy. The specific focus is on the performance standards required by the
Clean Air Act Amendments (CAAA) which require firms that store or use certain
chemicals to develop a Risk Management Plan (RMP) for reducing the likelihood and
impact of accidents at their plants. Data from a series of case studies and
interviews of executives in chemical firms reveal that proactive companies
integrated many of the requirements of the CAAA into their management systems
prior to the regulatory requirements. Most of these firms tend to be large ones.
Small firms often lack the resources to implement these regulations and hence
have tended to have a more difficult time with compliance.
PMID- 9637075
TI - Utilizing third-party inspections for preventing major chemical accidents.
AB - This paper proposes using certified third parties, coupled with Model Risk
Management Programs (Model RMPs), to implement EPA's Proposed Rule on the
prevention of chemical accidental releases. We concentrate on the insurance
aspects of this third-party approach and show that it could enable insurers to
more cost-effectively provide coverage against the risks of chemical accidental
releases. The third-party approach may also signal the facility's safety and
reduce the enforcement costs of regulations.
PMID- 9637076
TI - A pharmacokinetic study of occupational and environmental benzene exposure with
regard to gender.
AB - Using physiologically-based pharmacokinetic (PBPK) modeling, occupational,
personal, and environmental benzene exposure scenarios are simulated for adult
men and women. This research identifies differences in internal exposure due to
physiological and biochemical gender differences. Physiological and chemical
specific model parameters were obtained from other studies reported in the
literature and medical texts for the subjects of interest. Women were found to
have a higher blood/air partition coefficient and maximum velocity of metabolism
for benzene than men (the two most sensitive parameters affecting gender-specific
differences). Additionally, women generally have a higher body fat percentage
than men. These factors influence the internal exposure incurred by the subjects
and should be considered when conducting a risk assessment. Results demonstrated
that physicochemical gender differences result in women metabolizing 23-26% more
benzene than men when subject to the same exposure scenario even though benzene
blood concentration levels are generally higher in men. These results suggest
that women may be at significantly higher risk for certain effects of benzene
exposure. Thus, exposure standards based on data from male subjects may not be
protective for the female population.
PMID- 9637077
TI - Lognormal distributions for total water intake and tap water intake by pregnant
and lactating women in the United States.
AB - Using probability plots and Maximum Likelihood Estimation (MLE), we fit lognormal
distributions to data compiled by Ershow et al. for daily intake of total water
and tap water by three groups of women (controls, pregnant, and lactating; all
between 15-49 years of age) in the United States. We also develop bivariate
lognormal distributions for the joint distribution of water ingestion and body
weight for these three groups. Overall, we recommend the marginal distributions
for water intake as fit by MLE for use in human health risk assessments.
PMID- 9637078
TI - Analysis of exogenous components of mortality risks.
AB - A new technique for deriving exogenous components of mortality risks from
national vital statistics has been developed. Each observed death rate Dij (where
i corresponds to calendar time (year or interval of years) and j denotes the
number of corresponding age group) was represented as Dij = Aj + BiCj, and
unknown quantities Aj, Bi, and Cj were estimated by a special procedure using the
least-squares principle. The coefficients of variation do not exceed 10%. It is
shown that the term Aj can be interpreted as the endogenous and the second term
BiCj as the exogenous components of the death rate. The aggregate of endogenous
components Aj can be described by a regression function, corresponding to the
Gompertz-Makeham law, A(tau) = gamma + beta x e alpha tau, where gamma, beta, and
alpha are constants, tau is age, A(tau) [symbol: see text] tau = tau j identical
to A(tau j) identical to Aj and tau j is the value of age tau in jth age group.
The coefficients of variation for such a representation does not exceed 4%. An
analysis of exogenous risk levels in the Moscow and Russian populations during
1980-1995 shows that since 1992 all components of exogenous risk in the Moscow
population had been increasing up to 1994. The greatest contribution to the total
level of exogenous risk was lethal diseases, and their death rate was 387 deaths
per 100,000 persons in 1994, i.e., 61.9% of all deaths. The dynamics of exogenous
mortality risk change during 1990-1994 in the Moscow population and in the
Russian population without Moscow had been identical: the risk had been
increasing and its value in the Russian population had been higher than that in
the Moscow population.
PMID- 9637079
TI - [Value of imaging in the assessment of malignant fibrous histiocytoma of the soft
tissues].
AB - Malignant fibrous histiocytoma (MFH) is a rare and potentially highly malignant
sarcoma. The authors report 6 cases of MFH in various sites: two in the chest
wall, one in the pelvis, two in the gluteal zones and one on the scalp.
Ultrasonography and computed tomography were the main imaging methods used in the
assessment of the structure and extension of the tumor. A poor prognosis was
noted in four cases: death within a few months in the two thoracic sites,
recurrence in the pelvic and scalp lesions, radical surgery allowed recovery in
two cases. A review of the literature showed that MRI and CT are complementary in
the initial staging and follow-up of these patients.
PMID- 9637080
TI - [Ultrasound signs of pseudoneoplastic forms of hepatic hydatid cysts. A
prospective analysis of 50 cases].
AB - Pseudoneoplastic hydatid cyst of the liver (type IV), still raises diagnostic
difficulties on ultrasonography (US), and often leads us to perform computed
tomography. We therefore, conducted a prospective study of 50 cases of hepatic
hydatid cyst (HHC) type IV in order to define the US and Doppler features
allowing easy diagnosis with the best cost-effectiveness ratio. HHC type IV
represented 23.7% of all types. The average age was 43.5 years with a female
predominance. Many signs were described and their frequency was established. The
main signs were daughter cysts (82%), hypo or hyperechoic spirals (66%), and
peripheral transonic collarette (54%). At least one of these signs was present in
90% of cases. The Doppler study showed the avascular nature of the lesion in 100%
of cases. Hydatid serology using modern immunologic techniques confirmed the
diagnosis in 74% of cases. The US-serology combination can establish the positive
diagnosis of HHC type IV in 94% of cases. Computed tomography therefore has a
small place in this setting.
PMID- 9637081
TI - [Contribution of imaging in the diagnosis of pulmonary alveolar proteinosis.
Apropos of 3 cases].
PMID- 9637082
TI - [Leiomyosarcoma of the inferior vena cava and magnetic resonance imaging].
AB - Venous leiomyosarcomas are rare and predominantly arise in the inferior vena cava
(IVC). The clinical findings, often not very suggestive and nonspecific,
sometimes precede the diagnosis by several years. According to the literature,
leiomyosarcoma of the IVC generally occurs in middle-aged women. Modern imaging
techniques, especially magnetic resonance imaging (MRI) can now establish the
diagnosis of leiomyosarcoma of the IVC with a high probability and allow
assessment of operability. The authors report a case of leiomyosarcoma of the IVC
in a 24-year-old male patient, confirmed by intravenous biopsy. They present the
MR features of this malignant tumour, rarely reported in the literature, and
emphasize the value of this examination in the operability staging. The 3D
imaging provided by MRI allows intra and extraluminal staging and involvement of
adjacent organs. It also allows optimal evaluation of the effects on flow,
circulatory slowing or thrombosis and, due to its high contrast resolution, it is
more sensitive to distinguish clot from tumour nodule.
PMID- 9637083
TI - [Upper esophageal duplication. Apropos of a case disclosed by respiratory
distress].
AB - The authors report a new case of cystic oesophageal duplication, discovered in a
10-month-old infant. This case is unusual because of its site: thoraco-cervical,
and its acute clinical manifestations: respiratory depression. A surgical
resection was performed after Barium swallow, chest X-ray and ultrasonography.
Surgery ensured rapid clinical improvement. Pathology confirmed the diagnosis of
cystic oesophageal duplication.
PMID- 9637085
TI - [Hereditary osteo-onychodystosis. Apropos of 2 orthopedic cases].
PMID- 9637084
TI - [Peritoneal splenosis. Apropos of a case: contribution of ultrasonography and
computerized tomography].
AB - The authors report a case of peritoneal splenosis: the initial diagnosis was
established at ultrasound examination and CT scan. This unusual lesion must be
suggested when the past history is significant, as asymptomatic should not be
removed.
PMID- 9637086
TI - [Renal needle biopsy in children. Technical aspects and results].
AB - Renal needle biopsy is still irreplaceable in children. The objectives of this
retrospective study were to specify the technical aspects and the main
nephropathies encountered. 152 children under the age of 16 years (13 +/- 3), 79
boys and 73 girls, underwent renal biopsy. The biopsy was performed after
radiographic detection in 71 cases, and under continuous ultrasound guidance in
81 cases. The comparative study of these 2 techniques revealed the superiority of
continuous ultrasound guidance, allowing biopsy of an essentially cortical
fragment, rich in glomeruli with a limited number of punctures. Histological
examination showed a predominance of glomerular nephropathy with, especially,
visually normal kidney and membranoproliferative glomerulonephritis. These data
encourage us to perform ultrasound-guided RNB in children and to eradicate sites
of infection, particularly involving the upper respiratory tract.
PMID- 9637087
TI - [Pyramido-lunar fusion in black Africans. Apropos of 32 cases].
AB - Lunotriquetral coalition is a congenital carpal anomaly rarely discovered in a
white population. In the black population, most cases have concerned blacks in
America, Australia and South Africa. In the Sub-Saharia area, in Senegal, the
authors, after 8 incidental cases, report 32 lunotriquetral coalitions collected
in 20 patients. This retrospective study comparatively analysed 361 X-rays of the
wrist performed between February 1989 and July 1992 in the Orthopaedic and
Traumatologic Center (CTO) in Dakar. The bony coalition was bilateral in 12
patients and unilateral in the other 8 cases. The complete form (type III) was
the most frequent (46.8%). In the bilateral forms, 5 patients presented this
complete form. Lunotriquetral coalition was associated, in absence of congenital
abnormalities, with a synovial cyst of the wrist (2 cases), scaphoid fracture (1
case), non-union of a scaphoid fracture (1 case) and osteoarthritis of the wrist
(2 cases). After review of the literature, the authors discuss racial factors,
anatomo-radiographic forms and associated injuries.
PMID- 9637088
TI - [Contribution of imaging in intestinal intussusception in the adult. Apropos of a
case of ileocolic intussusception secondary to cecal lipoma].
AB - On the basis of a case of ileocolonic intussusception in a 35-year-old patient
secondary to an obstructive lipoma of the caecum, the authors review the
literature and discuss the clinical and radiological aspects of this disease. The
diagnosis was established by CT scan and barium enema before surgery. Adult
intussusception is a rare disease, which does not have any specific clinical
features. Radiological imaging is the only complementary investigation which can
suggest the diagnosis.
PMID- 9637089
TI - [Audiological management of children with malformations of the ear].
AB - All cases of malformation of the ear must undergo audiological assessment. Before
the age of 6 months, evoked auditory potentials during natural sleep will give
information on the threshold for the high frequencies in both ears, and will
confirm that the inner ear is functioning. After the age of 6 to 7 months,
subjective tests are used to demonstrate the bone conduction thresholds and
sometimes (depending on the degree of cooperation of the child) 1 or 2 air
conduction curves. When the malformation is unilateral, and the hearing is normal
on the opposite side, regular follow-up is required. When the malformation is
bilateral, or unilateral in conjunction with a sensorineural hearing loss in the
opposite ear, the child must be treated as a deaf child, and provided with a
hearing aid.
PMID- 9637090
TI - [Cochlear implants in the elderly].
AB - The authors present a retrospective and multicenter study of 18 elderly patients
aged above 60 years-old who underwent a cochlear implantation by comparing them
with a population of adult patients. The purpose of this study is to evaluate the
utility and benefits of cochlear implantation in the elderly by analyzing the
clinical data and the results of a questionnaire assessing the use of the implant
and the consequences of implantation on the quality of life. The results of this
study indicate that the improvement of quality of life in the elderly is similar
compared to a control group of adult patients.
PMID- 9637091
TI - [Conservation of residual hearing after cochlear implantation].
AB - Indications for cochlear implantation have been expanded to include severely
hearing impaired adults and may increase the number of patients presenting with
preoperative residual hearing. Conservation of residual hearing may allow better
performance with an implant. However, conventional thought is that implantation
destroys auditory structures involved in residual hearing. This study was
undertaken to assess if there are general or surgical factors intervening in the
conservation of residual hearing in a sample of multichannel implant recipients.
A retrospective study on 50 adult cochlear recipients with preoperative residual
hearing has been undertaken. Sixteen of 50 implanted subjects (32%) were found to
have conserved their residual hearing. Among them, seven patients have clinically
non-significant changes of hearing. Age, side of implantation, gender and
etiology did not influence the outcome of residual hearing. Round window
ossification, ossification of the cochlea, length of insertion, approach and site
of insertion (scala tympani vs.scala vestibuli) were not found to be
statistically significant between the population having lost and the population
having conserved residual hearing. This study emphasizes the need to undertake a
larger multicenter longitudinal study to determine the existence of factors
related to the conservation of residual hearing.
PMID- 9637092
TI - [From the classification of dysarthria to therapeutic concepts].
AB - The wide definition of dysarthria includes not only involvement of speech and
language, but also of the voice. The authors put forward a classification which
is based more logically on the mechanisms of the disorders as they present, and
which can at the same time serve as a guide to treatment.
PMID- 9637093
TI - [Presentation of various treatments proposed for dystonic dysarthria].
AB - Dystonia is characterised by purposeless muscle contractions, and can be
expressed in many clinical forms, those involving the head and neck may cause
problems with phonation, respiration or deglutition. The authors describe the
various treatment options, both therapeutic, medical, rehabilitative and
surgical.
PMID- 9637094
TI - [Comparison of different phonetic materials for perceptive analysis of
dysphonia].
AB - The authors describe a prospective study whose aim was to analyse the influence
of the choice of phonetic material on the judgment of the panel. De Krom has
already reported an experiment in which perceptive analysis showed that a
sustained vowel was a useful material provided that the attack transitory was
included (so called complete sustained vowel). He also showed that the panel gave
more consistent results with speech or the complete sustained vowel than with the
stable part of the sustained vowel. Our first objective was to find out whether
we agreed with Krom's results, because for the study in the Dutch language to be
applied to the French language, it was necessary to carry out an experimental
validation given the cultural differences which might prejudice the results. In
additional, we thought it likely that some acoustic information which was present
in the attack transitories and was lacking in the stable part of the sustained
vowel would run the risk of under-valuing the dysphonia in a study carried out on
the stable part of sustained vowels. Our second objective was therefore to
demonstrate that in cases of dysphonia, assessment based on the stable part of
sustained vowels would be more lenient than those based on speech. The study was
carried out using 80 voice samples from 60 dysphonic patients and 20 control
subjects. The panel was made up of 7 experienced listeners. Agreement in the jury
was judged by the percentage of identical responses given on 3 different
presentations of each speech sample. This study showed no differences in the
agreement of panel members over the three types of material by changing the
severity of classification by the panel was analysed as follows: 1--Pearson r
correlation coefficient, comparing on the one hand speech (the reference
variable), and on the other samples of the complete vowel and the isolated stable
part of the valve (tested variables). 2--A linear regression analysis. Our
results confirm that assessments carried out on a sustain/vowel tend to cause a
more lenient assessment than those carried out on speech. The assessment carried
out on sustained vowels when the attack transient is included were of similar
valued to those carried out using speech.
PMID- 9637095
TI - [Gastroesophageal reflux and dysphonia in children].
AB - With the exception of congenital anomalies, the aetiology of dysphonia in
children is often unknown. Yet, in adults, GOR has been shown to play an
important role. 22 children (aged between 2 and 14 years, 14 boys and 8 girls),
who had been suffering from a chronic dysphonia for more than six months were
seen at consultation. After a clinical ENT examination including a fibreoptic
laryngoscopy, each child had a long duration pH-study that lasted approximately
24 hours. Using the classical criteria for GOR, a pathological GOR was discovered
in 14 children, ie 64%. Analysis of the pH traces revealed that the vast majority
of refluxes occurred when the child was awake. CONCLUSION: more than 64% of
children suffering from chronic dysphonia had pathological GOR. The pH traces
highlighted that the majority of these refluxes occurred when the child was
awake.
PMID- 9637096
TI - [Is laryngeal papillomatosis always juvenile?].
AB - After recording an increased frequency of adult-onset recurrent respiratory
papillomatosis, the authors propose a multicentric investigation. The aim of the
investigation is to determinate the frequency of the new cases and their clinical
form. The preliminary results confirm the increased frequency of the adult-onset
form and show the possibility of a clinical form change.
PMID- 9637097
TI - [Idiopathic recurrent paralysis. Retrospective analysis of 67 cases].
AB - Sometimes incorrectly termed paralyses, idiopathic abnormalities of laryngeal
movement pose many problems about their physiopathological mechanism and
treatment. In an analysis of 67 cases, the outcome as far as the voice was
concerned was favourable in 51 cases, but a return to normal mobility occurred in
only 26 cases. An important factor is the delay before treatment is instituted.
In addition to repeated investigation of the areas of ENT, neurology, chest and
speech therapy, laryngeal electromyography can yield useful information, and
should always be undertaken before surgery is advised. As long as the clinical
conditions remains unimproved, the question of its idiopathic nature must be
constantly reviewed. A multicentre standardised investigation into this condition
would seem desirable to shed further light on its pathology and outcome.
PMID- 9637098
TI - [Early, middle-latency and late auditory evoked potentials in a case of acquired
epileptic aphasia (Landau-Kleffner syndrome)].
AB - The authors report the case of a girl whose development was normal until the age
of eleven when epileptic seizures occurred. These were followed by loss of speech
and auditory agnosia. The diagnosis of Landau-Kleffner syndrome was mode. The
study of the auditory evoked response showed normal function of ear and brainstem
auditory relays. On the other hand, the amplitude of the middle latency and late
cortical responses were decreased. The relationship between these
electrophysiological abnormalities and auditory agnosia are discussed.
PMID- 9637099
TI - [Objective tinnitus and velar myoclonus: apropos of a case of a child].
AB - The syndrome in which velar myoclonus is associated with objective tinnitus is
rare, and in the adult corresponds most commonly with a lesion in the dentato
rubro-olivary tract. In the child, no lesion can usually be found. The disorders
of function resulting from this syndrome are very disabling. Many forms of
treatment have been proposed, and the results have been found to be
disappointing. The authors report the case of a child in which muscle relaxants
were used to very good effect, and emphasize the fact that the natural history of
the condition in childhood is one of spontaneous remission, so that aggressive
treatment is not appropriate.
PMID- 9637100
TI - [ORL and speech aspects in DiGeorge syndrome].
AB - The DiGeorge syndrome presents clinically as a combination of a congenital
cardiopathy with immune deficiency and predisposition to infections, signs of
hypoparathyroidis with severe hypocalcaemia in the neonatal period, and facial
dysmorphism. New techniques in molecular cytogenetics (in-situ fluorescent
hybridisation--FISH) have provided evidence of microdeletion of chromosome 22q11
in most cases of the DiGeorge syndrome. There is an important overlap between
this syndrome, the velo-cardio-facial syndrome, and certain other cono-truncal
cardiac anomalies which are linked with the same microdeletion syndrome. Basing
their observation on a case of the partial syndrome, the authors emphasise the
otological and maxillo-facial aspects, and especially the effects on speech and
language. It is essential to carry out repeated audiometric testing to exclude an
audiometric cause for the speech and language problems. At the same time,
thorough speech and language assessment is necessary to establish the degree of
velar insufficiency (rhinolalia). These will guide the speech therapy
rehabilitation, and quantify the psycho-affective component. Surgery on the
palate may be a possibility, depending on the progress in speech and language
improvement.
PMID- 9637101
TI - Screening for otitis media with effusion in Chinese schoolchildren: a pilot
study.
AB - Otitis media with effusion (OME) is a common childhood otological condition. The
treatment of OME with myringotomy and grommet insertion is the commonest surgical
procedure performed on children worldwide. Although the figure for the prevalence
of OME is widely known in Caucasian children, figures are lacking for Chinese
children. A pilot study for the prevalence of OME in Hong Kong Chinese
schoolchildren was undertaken by the investigators on a group of 255 children
with ages ranging from 6 to 7 years old. A point prevalence rate of 1.56% of OME
was found. This is noticeably lower than studies in the West where the reported
prevalence ranges from 2.3% to 14% in age compatible children. The epidemiology
of OME and the methodology for population screening of OME are reviewed and
discussed. The preliminary findings of this study would be a useful indicator for
the estimation of study group size in a full epidemiological study of OME in
Chinese children as well as providing valuable insight into the technical
difficulties involved.
PMID- 9637102
TI - [Malignant nasosinusal melanomas. Review of the literature apropos of 12 cases].
AB - Malignant melanoma with primary onset in the nasal cavity and paranasal sinuses
remains a scarcely encountered malignancy and we report 12 cases of our own
experience from 1991. These mucosal melanomas occur mainly in the elderly and
present most commonly as a one sided airway obstructive syndrome with often
bleeding in the nasal cavity. No sex or race ratio is found. Histological
examination of the surgical specimen has been made easier since the use of
immunohistochemical studies. The original site of onset is commonly located at
the inferior part of the nasal cavity but in many cases, it is noted several
sites of tumor localization. Despite well conducted treatment the prognosis
remains quite deceiving and significantly poor. In our study, the 4-year
actuarial survival was 26%. The 5-year survival rate ranges in the literature
from 10% to 40%. Short and long term follow-up show an important rate of
recurrence (local and lymph node metastases as well as distant metastases). The
insidious evolution of the malignancy usually happens during the first year.
Computed tomography and MRI are essential in the evaluation of tumor extension.
The treatment is based on the combination of surgery and radiotherapy: Surgery is
practised first and must ensure sufficient excision of the tumor without minimal
functional or aesthetic damage in this complex region. This surgery is based on
surgical approaches to the midface known as Lateral rhinotomy and midfacial
degloving. When there is cervical lymph node involvement at the time of diagnosis
it is suitable to treat it, even in case of recurrence. Complementary high dose
radiation is required to treat tumors which could not undergo surgery and also as
adjuvant therapy after removal of the mass.
PMID- 9637103
TI - Identification of the HSV-1 genome by "Dot Blot hybridization" in the geniculate
ganglion of rabbits.
AB - Herpes simplex Virus type 1 (HSV-1) was inoculated into 48 rabbits by 3 different
routes: 10 rabbits were dosed by mouth, 18 rabbits injected in the tongue and 14
injected in the perineurium of the facial nerve at its entrance into the
stylomastoid foramen. Some of the animals were killed after a week and others
after three weeks. Facial palsy was produced in none of the cases. Seroconversion
was demonstrated in the peripheral blood of 100% of the inoculated animals.
Cultures of macerate of the facial nerve and geniculate ganglion, as well as of
the ipsilateral medulla, were negative. DNA from HSV-1 was found by "Dot Blot
hybridization" technique in 30% of the macerates of the geniculate ganglion and
facial nerve and in 60% of the medulla macerate in those animals killed after one
week and in 0% of both samples in those killed in the third week. The fact that
the HSV-1 could be isolated in the geniculate ganglion of the facial nerve
continues to support the possibility of this virus as the causal agent for facial
palsy, either as a single disease or associated with other symptoms.
PMID- 9637104
TI - Waldeyer's ring lymphomas: an epidemiological study of 55 cases.
AB - Waldeyer's ring is a relatively common location for non-Hodgkin's lymphoma. Here,
we report an epidemiological study of Waldeyer's ring lymphomas based on data for
55 cases treated over a 19-year period at three centers in northern Spain. In
most respects our results confirm those of previous studies. The average delay
between first consultation and diagnosis was 3.8 months, and was longer for
nasopharyngeal lymphomas than for tonsillar lymphomas.
PMID- 9637105
TI - [The N0 neck in patients treated by supraglottic laryngectomy: abstention,
surgery or radiotherapy?].
AB - The authors examined the therapeutical approach to the N0 neck in patients
submitted to supraglottic laryngectomy (SL). In these patients the choice of the
therapeutical protocol may consist of simple abstention, of neck dissection or of
elective radiotherapy: every decision has to be taken considering all specific
inconveniences of each option. In their report the authors examined the follow-up
of the N0 necks of 421 patients submitted to SL from 1970 to 1991. The patients
submitted to wait and see policy were 225 whereas 196 received uni- or bilateral
neck dissection. After the cervical failure's salvage the final 3-years control
of the neck was the same in the two groups (91.1% vs 91.4%). In a previous
research on 1157 N0 necks of patients submitted to total laryngectomy they
observed a 5-years cervical control of 88.8% after wait and see policy and of
92.3% after elective radiotherapy. The conclusions of the authors is that no one
of the two protocols is preferable to the other one and that subsequently in many
cases of supraglottic T1 and T2 cancers a wait and see policy may be justified in
absence of consistent counter-indications.
PMID- 9637106
TI - Tracheal ring rupture and herniation during percutaneous dilatational
tracheostomy identified by fibreoptic bronchoscopy.
AB - We present a case of rupture and herniation of cartilaginous tracheal rings into
the lumen of the trachea that was noticed as an incidental finding during
bronchoscopy after percutaneous dilatational tracheostomy. While percutaneous
methods of tracheostomy formation gain popularity in intensive care settings, the
number of reported problems associated with this technique continue to grow. We
propose that fibreoptic bronchoscopy used routinely with percutaneous
tracheostomy formation will identify a number of complications involving the
tracheal skeleton.
PMID- 9637107
TI - [Laryngeal tuberculosis: a diagnosis not to be forgotten].
AB - Tuberculosis of the larynx has become a rarity since the discovery of
streptomycin in 1944. In this article a personal case history is described,
together with a review of the literature and an analysis of the main clinical
features of tuberculosis of the larynx. The pseudo-tumoural form of tuberculosis
is often indicative of the presence of pulmonary tuberculosis, but may also occur
in isolation. Histology is often the only definitive diagnostic test.
PMID- 9637108
TI - [Lingual thyroid and intra-lingual thyroglossal cyst. Apropos of 2 cases].
AB - Lingual thyroid and intra lingual thyro-glossal cyst are two benign tumours of
similar embryological pathogenesis respectively with the arrest in the ectopic
position of the thyroid gland during its downward migration and from abnormal
persistence of the thyro-glossal tract for the cyst. The occurrence of lingual
thyroid is rare 1/100,000 patients and outnumbers the incidence of intra-lingual
cyst which represents an estimated 2.1% of the thyro-glossal cysts or fistulas.
Both lesions are a rare cause of dysphagia and dyspnoea due to oropharyngeal
obstruction, and radionuclide scintigraphy combined with CT and/or MRI will
establish the diagnosis. Surgical pharyngotomy with an infra-hyoid approach
provides excellent access to the lesions and complete removal of the tumours.
PMID- 9637109
TI - Diagnosis and treatment of lingual thyroid: a review.
AB - Lingual thyroid is a rare developmental anomaly. It occurs because of the
defective descent of thyroid tissue through the thyroglossal duct to its normal
pretracheal position. In this study, two patients who presented with a mass in
the oropharynx, finally diagnosed as lingual thyroid are presented, and the
literature is reviewed. The masses were 3 x 2.5 x 1.5 cm and 3.5 x 3 x 3 cm in
size. The diagnosis was based on the clinical features, fine needle aspiration
biopsy, laboratory tests and radiographic imaging studies. The first case was
treated medically with thyroxine. No treatment was given for the second case
because of the patient's refusal. Both cases have not required additional therapy
so far.
PMID- 9637110
TI - [Chronic osteomatous otitis media: apropos of 2 cases].
AB - Osteomatous chronic otitis media is an extremely rare clinical entity. Fleury has
described three types: a massive type, a diffuse attico-antral type, and a
localised type. This latter is equivalent to a state of chronic inflammation of
the middle or outer ear, accompanied by bony excresscences of osteomatous type.
Here we add two additional cases to the few which are to be found in the
literature on this subject. We would also like to emphasize the practical
surgical difficulty of treating such cases, with the vital structures of the
middle ear hidden (facial nerve, lateral semicircular canal, and ossicles), and
would advise the greatest care when tackling these surgically.
PMID- 9637111
TI - [Pulsatile tinnitus caused by pre-auricular post-traumatic vascular lesions:
apropos of a case].
AB - Pulsatile tinnitus associated with a pulsating swelling were the presenting
clinical features of a patient who had suffered contusion to the pre-auricular
area. The diagnosis of arteriovenous fistula (AVF) was made, and the child
underwent operation. The pathology of this condition is reviewed.
PMID- 9637112
TI - Nasal chondroma: a case report and review of the literature.
AB - Although rare tumors, chondromas will on occasion be encountered by the
otolaryngologist in his routine daily practice. The authors describe a nasal
myxochondroma in an 8-year-old child, which was removed satisfactorily
surgically, with no signs of recurrence even after 4 years of follow-up. Because
chondromas may also present as nasal polyps, the knowledge of cartilaginous
tumors in the nose plays a pivotal role for a better approach to these patients.
PMID- 9637113
TI - [Hypoglosso-facial anastomosis: results and technical development towards end-to
side anastomosis with rerouting of the intra-temporal facial nerve (modified May
technique)].
AB - The authors report their experience with 31 hypoglosso-facial anastomoses mainly
carried out after removal of tumours of the cerebello-pontine angle, 26 were
available for evaluation: at 18 months there were 5 of grade II, 19 of grade IV
and 2 of grade V. Only one patient was dissatisfied with the result. 24 of the
patients had received their hypoglosso-facial anastomosis using the clinical
technique of Korte. In 3 cases the operation was by the technique of May. The
authors suggest a variation of May's technique: it was carried out on the last 4
patients. It consists of a hemi-hypoglosso-facial anastomosis with rerouting of
the mastoid portion of the facial nerve, without using a nerve graft. The aim of
this technique is to reduce the sequelae of hemi-lingual atrophy and paralysis
(which gives trouble with articulation, mastication and deglutition). The
authors' experience confirms that these sequelae are greatly reduced, if not
abolished. The functional results in terms of facial movements were satisfactory
and consistant: 43.7% were quantified--with 3 of grade II and one of grade IV on
the House Brackmann scale.
PMID- 9637114
TI - [External otitis].
PMID- 9637115
TI - GnRH agonists and add-back therapy: is there a perfect combination?
PMID- 9637116
TI - Can women at risk of cervical abnormality be identified?
AB - OBJECTIVE: To determine if use of a detailed risk factor profile accurately
predicts the presence of cytological abnormality of the cervix or improves the
appropriateness of referral for colposcopic assessment when women are found to
have these abnormalities. DESIGN: Cross-sectional survey. SETTING: Family
planning clinic. POPULATION: 1219 consecutive women, aged between 15 and 19
years, attending for contraceptive advice. Variables included age, social class,
educational status, hormonal and obstetric history, smoking and alcohol habits,
history of sexually transmitted diseases, the age of first intercourse, number of
sexual partners, duration of each relationship, frequency of intercourse,
contraception used and the age of each partner. MAIN OUTCOME MEASURES: Presence
or absence of cytological abnormality and the presence or absence of histological
abnormality in those with cytological abnormality referred for colposcopic
assessment. RESULTS: Univariate analysis confirmed many of the known associations
of cervical abnormality. Discriminant analysis identified five independent
significant predictors of cytological abnormality and four independent predictors
of dyskaryotic cytology. At best models, derived from identified variables
correctly predicted 10.1% of individuals with cytological abnormality and 13.5%
of those with dyskaryotic cytology. Of those referred for colposcopic assessment
because of abnormal cytology, models were able to predict 23.5% of those with
histological evidence of cervical intraepithelial neoplasia. CONCLUSIONS: Despite
the availability of detailed information regarding the known correlates of
cervical neoplasia in this age group, it was not possible to identify the
majority of women with cervical abnormality. It is concluded that the strength of
these associations is not sufficient to allow useful prediction of membership of
a high risk group.
PMID- 9637117
TI - A systematic review and meta-analysis of family history and risk of ovarian
cancer.
AB - OBJECTIVE: To estimate the relative risk and lifetime risk of ovarian cancer in
women with various categories of family history. DESIGN: A meta-analysis of all
published case-control and cohort studies. METHODS: Pooled relative risk
estimates were calculated for the case control studies, using the Mantel-Haenzel
method. These estimates were combined with the relative risks from the cohort
studies. The pooled estimates of relative risk were used to estimate lifetime
risks of ovarian cancer from age 15 up to age 75, for various categories of
family history. MAIN OUTCOME MEASURES: Relative risks and lifetime risks of
developing ovarian cancer were calculated for the categories of women with 1. an
affected first degree relative; 2. an affected mother; 3. an affected sister; and
4. women with more than one affected relative. RESULTS: The relative risk to
first degree relatives is 3.1 (95% CI 2.6-3.7). There is some evidence that this
relative risk declines with age. The relative risk to mothers of cases 1.1 (95%
CI 0.8-1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9-5.1),
and daughters: 6.0 (95% CI 3.0-11.9); the explanation of this difference is
unclear. CONCLUSIONS: Women with a family history of ovarian cancer have a
substantially higher risk of developing ovarian cancer compared with women
without such a history. However the risk is small for most categories of family
history, except for the small number of individuals who have more than one
affected relative.
PMID- 9637118
TI - Value of magnetic resonance imaging with an endovaginal receiver coil in the pre
operative assessment of Stage I and IIa cervical neoplasia.
AB - OBJECTIVE: To assess the value of high resolution endovaginal magnetic resonance
images (MRI) of the uterine cervix in planning management of early cervical
cancer. DESIGN: Prospective cross-sectional study. SETTING: Specialist
gynaecological oncology unit of a postgraduate teaching hospital. PARTICIPANTS:
Thirty nine women aged 25-76 years old (mean 42.5 years) with invasive carcinoma
Stage I or IIa of the cervix. METHODS: A ring coil was positioned endovaginally
around the cervix. Imaging was performed on a 1.0 T HPQ Vista or 0.5 T Asset
(Picker, Highland Heights, Ohio, USA) using T1 weighted and T2 weighted sequences
in transverse and sagittal planes with thin slices (2.5 mm) and small fields of
view (12 cm). Tumour volumes were measured and any extension into adjacent organs
and parametrium was noted. The patients were followed up after treatment and the
outcome related to the MRI findings. RESULTS: There was one false positive and
one false negative result among five Stage Ia patients being assessed for
residual disease after cone biopsy or LLETZ. The MRI assessment of the size and
distribution of the tumour was confirmed histologically in all 31 patients with
Stage Ib or IIa disease who were treated surgically. One of these patients in
whom no endocervical tumour was visible on MRI underwent radical trachelectomy.
Three patients had radiotherapy as primary treatment. Patients with Stage Ib or
IIa disease who had tumour volumes > 10 cm3 with early parametrial extension on
MRI had a substantially worse prognosis at 24 months (disease-free survival 58.3%
vs 95.5%, P = 0.003). CONCLUSION: High resolution MRI with an endovaginal coil
allows precise measurement of tumour volume and identifies patients with small
volume disease who might be considered for more conservative therapy. This
technique also reveals early parametrial invasion that cannot be identified
reliably by any other method. Early parametrial invasion in women with large
tumours appears to have a very much worse prognosis.
PMID- 9637119
TI - Pre-operative serum level of tumour-associated trypsin inhibitor and residual
tumour size as prognostic indicators in Stage III epithelial ovarian cancer.
AB - OBJECTIVE: To evaluate the use of the pre-operative tumour-associated trypsin
inhibitor (TATI) level and residual tumour size at primary surgery as a
prognostic indicators for patients with Stage III epithelial ovarian cancer.
DESIGN: Retrospective cohort study. SETTING: Department of Obstetrics and
Gynaecology, University Hospital, Helsinki, Finland. PARTICIPANTS: Ninety-eight
women with Stage III ovarian cancer. METHODS: TATI was measured by
radioimmunoassay from serum samples obtained within one week before surgery. A
cutoff value of 22 microg/L was used. Multivariate analysis included pre
operative TATI level, age, histologic grade and histologic type. Mantel-Cox test
was used for calculating statistical significance of differences in survival
between groups. MAIN OUTCOME MEASURES: Cumulative five-year survival, pre
operative serum TATI level and residual tumour size. RESULTS: Surgery was optimal
(residual tumour size < or = 2 cm) in 55 patients and suboptimal (residual tumour
size > 2 cm) in 43. Pre-operative TATI level < or = 22 microg/L predicted better
prognosis both in patients with optimal and suboptimal surgery compared with
patients with pre-operative TATI level > 22 microg/L. Patients with optimal
surgery and a pre-operative TATI > 22 microg/L had a twofold relative risk of
death compared with those with a pre-operative TATI < or = 22 microg/L. The
cumulative survival was less than three years for patients with suboptimal
surgery and pre-operative TATI > 22 microg/L. CONCLUSIONS: Pre-operative serum
TATI in combination with residual tumour size may be useful in stratifying
patients with Stage III ovarian cancer into different categories in randomised
treatment trials.
PMID- 9637120
TI - A comparative study of pre-operative procedures to assess cervical invasion by
endometrial carcinoma.
AB - OBJECTIVE: To compare the accuracy of different diagnostic procedures currently
used to assess cervical involvement in endometrial carcinoma. DESIGN:
Retrospective observational study. SETTING: Department of Obstetrics and
Gynecology, Shinshu University Hospital, Matsumoto, Japan. PARTICIPANTS: Sixty
four patients with endometrial carcinoma were evaluated pre-operatively for
cervical involvement by six different diagnostic procedures: cervical cytology,
endocervical curettage, transvaginal ultrasonography, hysteroscopy, magnetic
resonance imaging, and serum levels of CA125. The number of positive and negative
diagnoses of cervical invasion by each of these procedures were correlated with
the actual invasion determined by histological examination. RESULTS: Cervical
invasion was confirmed in 12 (18.8%). Endocervical curettage showed high
sensitivity (91%), the highest negative predictive value (96%), and the lowest
negative likelihood ratio (0.14). Hysteroscopy showed high positive likelihood
ratio (8.2) and low negative likelihood ratio (0.20). Magnetic resonance imaging
showed the highest positive predictive value (75%) and the highest positive
likelihood ratio (12.5). Magnetic resonance imaging was excellent for predicting
stromal invasion, whereas hysteroscopy was superior for assessing mucosal
involvement to magnetic resonance imaging. CONCLUSION: Endocervical curettage is
a good test for excluding cervical involvement by endometrial carcinoma.
Hysteroscopy is a good test in making both positive and negative diagnoses for
cervical involvement. Magnetic resonance imaging is an excellent test for
detecting cervical involvement, especially when the stroma is invaded.
PMID- 9637121
TI - Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300
patients from a multi-centre study. International Collaborative Uterine Thermal
Balloon Working Group.
AB - OBJECTIVE: To evaluate the safety and efficacy of thermal balloon therapy for
menorrhagia. DESIGN: Prospective, observational study. SETTING: Fifteen centres
in Canada and Europe. POPULATION: Two hundred and ninety-six eligible women for
whom follow up data were available for three months or more. Eligible women
included those for whom further fertility was not a concern, were not
postmenopausal, suffered from intractable menorrhagia, had a normal uterine
cavity, and who were fully informed regarding the investigational nature of
uterine thermal balloon therapy. METHODS: Three hundred and twenty-one procedures
of balloon endometrial ablation were performed using the same protocol between
June 1994 and August 1996. Exclusion criteria included structural uterine
abnormality or (pre) malignant lesions. Treatment entailed controlled heating of
fluid in an intrauterine balloon. General anaesthesia was employed in the 61% of
procedures while local anaesthesia with or without sedation was used in 39% of
cases. ANALYSIS: Follow up data at 3 and/or 6, and/or 12 months were required for
inclusion in the analysis. A paired t test, Wilcoxon signed-ranks test, and
multiple and logistic regression analyses were used to evaluate the changes in
bleeding and dysmenorrhoea patterns, and possible confounding variables,
respectively. Success was defined as the subjective reduction of menses to
eumenorrhoea or less. RESULTS: No intra-operative complications occurred, and
post-operative morbidity was minimal. Success of the procedure was constant over
the year (range 88%-91%). Treatment led to a significant decrease in the duration
of menstrual flow and severity of pain (P < 0.0001). Increasing age, higher
balloon pressure, smaller uterine cavity, and a lesser degree of pre-procedure
menorrhagia were associated with significantly improved results. Pre-treatment
with gonadotrophin releasing hormone agonists increased amenorrhoea and spotting
rates (P = 0.03), but was only used in 5% of cases. CONCLUSION: Thermal balloon
endometrial ablation appears to be safe, as well as effective in properly
selected women with menorrhagia and is potentially an outpatient procedure.
PMID- 9637122
TI - Analysis of birthweight and gestational age in antepartum stillbirths.
AB - OBJECTIVE: To study the characteristics of birthweight and gestational age of
third trimester fetal deaths which occurred before the onset of labour. DESIGN:
Review of computerised confidential perinatal mortality records. Data originated
from the 1992 Trent Region Perinatal Mortality Survey. SAMPLE: One hundred and
forty-nine antepartum stillbirths of at least 24 weeks of gestation confirmed by
early ultrasound scan. Congenital abnormalities and multiple pregnancies were
excluded. MAIN OUTCOME MEASURES: Reported causes of stillbirth; weight-for
gestational age centiles based on a standard derived from normal pregnancies;
pregnancy characteristics compared with the local maternity population. RESULTS:
Of 149 stillbirths, 83 (56%) were preterm and 66 were at term, and the majority
(126; 85%) occurred from 31 weeks. Most of the deaths (97; 65%) were reported as
'unexplained' even though post-mortems had been carried out in 60% of all cases.
Using a gestational age-specific fetal weight standard derived from normal, term
live births, 41% of all cases of stillborn infants were small-for-gestational age
(< 10th centile; OR 6.2; 95% CI 3.3-11.5); 39% of which had been classified as
unexplained were small for gestational age (OR 5.6; 2.6-12.0). This excess of
small stillbirths was most pronounced between 31 and 33 weeks, where the weights
of 63% of all stillbirths and 72% of unexplained fetal deaths were < 10th
centile. Overall, a higher proportion of preterm (< 37 weeks) than term
stillbirths were small for gestational age: 53% vs 26% (OR 3.3; 1.6-6.5).
However, at term there were also more subtle differences in weight deficit, with
more fetuses with a weight between the 10th and 50th centiles than between 50th
and 90th (36 vs 11; OR 3.3; 1.4-7.8). Mothers of pregnancies ending in stillbirth
were similar in age, size, parity and ethnic group to mothers of live born
babies, but were more likely to be smokers (37 vs 27%, OR 1.6; 1.2-2.3).
CONCLUSIONS: Many stillborn babies are small for gestational age. In the absence
of significant differences in physiological pregnancy characteristics, this is
unlikely to be a constitutional smallness, but represents a preponderance of
intrauterine growth restriction. For a full appreciation of the strength of this
association, appropriate weight standards and classifications need to be applied
in perinatal mortality surveys. Many antepartum stillbirths which are currently
designated as unexplained may be avoidable if slow fetal growth could be
recognised as a warning sign.
PMID- 9637123
TI - Application of a customised birthweight standard in the assessment of perinatal
outcome in a high risk population.
AB - OBJECTIVE: Physiological as well as pathological variables influence birthweight.
The aim of the present study was to examine perinatal outcome in relation to
birthweight centiles applying a customised birthweight standard. METHODS: Two
hundred and seventeen babies from high risk pregnancies were evaluated and
classified as small or not small for gestational age according to two standards:
1. conventional Dutch birthweight centiles and 2. customised centiles which
adjust individually for physiological variables like maternal booking weight,
height and ethnic origin. RESULTS: Customisation of the weight standards resulted
in identification of an additional group of infants who were small for
gestational age, but not by the Dutch standards. These babies were associated
with significantly more adverse perinatal events than those who were not small
for gestational age as defined by a customised standard. CONCLUSIONS: Adjustment
of birthweight centiles for physiological variables significantly improves the
identification of infants who have failed to reach the expected birthweight and
who are at increased risk for adverse perinatal events.
PMID- 9637124
TI - Fetal growth velocity in the prediction of intrauterine growth retardation in a
low risk population.
AB - OBJECTIVE: To determine whether fetal growth velocity derived from two antenatal
ultrasound measurements in the third trimester, 28 days apart, can identify
infants born with anthropometric features of intrauterine growth retardation.
DESIGN: Prospective observational study. SETTING: Department of obstetric
ultrasound, Ninewells Hospital, Dundee. SUBJECTS: Two hundred and seventy four
low risk women participating in a longitudinal study of serial fortnightly
ultrasound in pregnancy. METHODS: Growth velocities of the fetal abdominal area
and bi-parietal diameter were calculated from the third from last and last
measurements prior to delivery. Receiver Operator Characteristics curves were
employed to determine an optimal cutoff point for velocity to predict
intrauterine malnourishment. MAIN OUTCOME MEASURES: Likelihood ratios for fetal
abdominal area and bi-parietal diameter growth velocity in the prediction of
growth retarded infants with skinfold thickness < 10th centile; ponderal index <
25th centile, or mid-arm circumference to occipito-frontal circumference ratio
(MAC:OFC ratio) of less than -1 SD. A likelihood ratio of > 10 generates
significant changes in the pre-test probability of growth retardation, whereas a
likelihood ratio of 5 to 10 generates only moderate changes. RESULTS: Fetal
abdominal area velocity predicted growth retardation with likelihood ratio 10.4
(95% CI 3.9 to 26) for skinfold thickness; likelihood ratio 9.5 (95% CI 4.6 to
19) for ponderal index; a likelihood ratio 4.7 (2.3 to 8.4) for MAC:OFC. Bi
parietal diameter velocity predicted growth retardation with likelihood ratio 6.5
(95% CI 1.9 to 20) for skinfold thickness but did not predict low ponderal index
or MAC:OFC ratio. CONCLUSIONS: Fetal abdominal area velocity is useful in
identifying infants with reduced skinfold thickness or low ponderal index.
Prospective evaluation of serial ultrasound and velocity calculation in a
selected population at increased risk of growth failure and a clearer
understanding of the relative significance of the different neonatal
anthropometric measures of impaired growth achievement is necessary before the
estimation of growth velocity can be recommended in clinical practice.
PMID- 9637125
TI - Optimising maternal-fetal outcomes in preterm labour: a decision analysis.
AB - OBJECTIVE: To compare, using decision analytic techniques, maternal and fetal
risk and benefits of three strategies for the management of preterm labour after
32 weeks. These strategies are empiric tocolysis, no tocolysis, or amniocentesis
for fetal maturity testing. DATA SOURCES: Published medical literature provided
the probabilities, including those for tocolysis efficacy, maternal and neonatal
outcomes, and steroid efficacy. DATA: Synthesis Separate decision trees were
created for hypothetical cohorts of patients presenting with preterm labour at
32, 34, and 36 weeks of gestation to compare strategies. The primary outcome was
the total number of expected adverse maternal and neonatal events for each
strategy at each gestational age. RESULTS: At 32 weeks tocolysis yielded the
lowest total number of adverse maternal and neonatal events. At 34 weeks, both
tocolysis and no tocolysis yielded similar overall outcomes. At 36 weeks most
clinical outcomes were good regardless of strategy. CONCLUSIONS: This analysis
supports the empiric use of tocolytics at 32 weeks. At 34 weeks, either tocolysis
or no tocolysis appear to be reasonable alternatives. At 36 weeks no tocolysis is
probably preferred. This analysis also suggests that amniocentesis should not be
employed in the management of preterm labour at these gestational ages.
PMID- 9637126
TI - Antenatal corticosteroid therapy and risk of osteoporosis.
AB - OBJECTIVE: To assess the risk of maternal osteoporosis associated with antenatal
corticosteroid administration for neonatal respiratory distress syndrome
prophylaxis. DESIGN: Prospective longitudinal study. SETTING: Maternity unit of
Chelsea and Westminster Hospital, London. POPULATION: Fourteen pregnant women who
received dexamethasone therapy for fetal lung maturation in anticipation of
delivery before 34 completed weeks of gestation. METHODS: Blood samples were
collected before dexamethasone administration, 24 hours and 48 hours after the
course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy
terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the
rate of bone formation, and serum levels of cross-linked carboxy terminal
telopeptide (ICTP) were measured as a marker of bone resorption. MAIN OUTCOME
MEASURES: Changes in the markers of bone turnover following dexamethasone
administration. RESULTS: Serum PICP levels dropped 24 hours after dexamethasone
therapy (P = 0.001), but partially recovered by 48 hours (P = 0.014) to reach
higher than pre-therapy levels at delivery (P = 0.044). Although there were no
corresponding changes in the serum levels of ICTP after 24 and 48 hours of
therapy, levels increased from pretherapy to delivery (P = 0.006). CONCLUSION:
Antenatal corticosteroid therapy leads to a transient suppression of, followed by
an increase in, bone formation without any significant alteration in the pattern
of bone resorption expected during pregnancy.
PMID- 9637127
TI - Antenatal glucocorticoid administration increases corticotrophin-releasing
hormone in maternal plasma.
AB - OBJECTIVE: This study was designed to determine whether maternal corticotrophin
releasing hormone (CRH) concentrations are altered after maternal betamethasone
administration for fetal lung maturity in women with threatened preterm labour
and whether these effects are dependent on gestational age. METHODS: Our study
included 49 women with threatened preterm labour who received prenatal
betamethasone for fetal lung maturity between 24 and 31 weeks of gestational age
and 11 women who did not. Maternal blood was taken before and after
glucocorticoid administration or at 24 hours after initial sampling. Plasma CRH,
adrenocorticotrophin (ACTH) and cortisol concentrations were determined by
radioimmunoassays. The women were stratified into 24-25 weeks, 26-27 weeks, 28-29
weeks, and 30-31 weeks completed gestation. RESULTS: At each gestational age,
maternal cortisol concentrations decreased by approximately 85% after
glucocorticoid administration. Overall mean cortisol values fell from 580.0 (SD,
351.8) to 89.7 (96.6) nmol/L (n = 40, P < 0.001). Overall mean ACTH values
decreased from 9.9 (4.7) to 5.0 (3.4) pmol/L (n = 43, P < 0.001), and the
approximate 50% decrease was similar at each gestational age. In marked contrast,
overall mean CRH values increased from 58.0 (37.0) to 87.8 (68.6) pmol/L (n = 49,
P < 0.001) after betamethasone administration. There was no change in maternal
cortisol, ACTH or CRH values over 24 hours in women who did not receive
betamethasone. CONCLUSIONS: We conclude that maternal betamethasone
administration increases maternal plasma CRH values between 24 and 31 completed
weeks of gestation.
PMID- 9637128
TI - Disproportionate fetal growth and fingerprint patterns.
AB - Fingerprint whorl patterns are formed during fetal life. In a group of 180 term
infants, those with more fingerprint whorls tended to have a small abdominal
circumference (P = 0.09) and high ratio of head to abdominal circumference (P =
0.008). These associations were independent of the relation between the whorl
counts of the mothers and their infants. We also found an independent correlation
between the babies' whorl count and the combination of increasing subscapular (P
= 0.03) and decreasing triceps (P = 0.02) skinfold thicknesses of the mothers.
Whorl patterns are associated with adult hypertension; maternal nutritional
status may influence their common origin during fetal development.
PMID- 9637129
TI - Maternal death due to cerebral toxoplasmosis.
PMID- 9637130
TI - The disappearance of fetal and donor red blood cells in alloimmunised
pregnancies: a reappraisal.
PMID- 9637131
TI - Unsuccessful treatment of missed abortion.
PMID- 9637132
TI - Menstrual cycle variation in mammographic breast density: so who cares?
PMID- 9637133
TI - Serum insulin-like growth factor-I levels and prostate cancer risk--interpreting
the evidence.
PMID- 9637134
TI - Pathology vs. prognosis: are hereditary cancers a different breed?
PMID- 9637135
TI - Herceptin raises its sights beyond advanced breast cancer.
PMID- 9637136
TI - Ashkenazi community is not unwilling to participate in genetic research.
PMID- 9637137
TI - Lag in colorectal screening rates prompts innovation.
PMID- 9637139
TI - Variation in mammographic breast density by time in menstrual cycle among women
aged 40-49 years.
AB - BACKGROUND: Mammography is less effective for women aged 40-49 years than for
older women, which has led to a call for research to improve the performance of
screening mammography for younger women. One factor that may influence the
performance of mammography is breast density. Younger women have greater
mammographic breast density on average, and increased breast density increases
the likelihood of false-negative and false-positive mammograms. We investigated
whether breast density varies according to time in a woman's menstrual cycle.
METHODS: Premenopausal women aged 40-49 years who were not on exogenous hormones
and who had a screening mammogram at a large health maintenance organization
during 1996 were studied (n = 2591). Time in the menstrual cycle was based on the
woman's self-reported last menstrual bleeding and usual cycle length. RESULTS: A
smaller proportion of women had "extremely dense" breasts during the follicular
phase of their menstrual cycle (24% for week 1 and 23% for week 2) than during
the luteal phase (28% for both weeks 3 and 4) (two-sided P = .04 for the
difference in breast density between the phases, adjusted for body mass index).
The relationship was stronger for women whose body mass index was less than or
equal to the median (two-sided P<.01), the group who have the greatest breast
density. CONCLUSIONS/IMPLICATIONS: These findings are consistent with previous
evidence suggesting that scheduling a woman's mammogram during the follicular
phase (first and second week) of her menstrual cycle instead of during the luteal
phase (third and fourth week) may improve the accuracy of mammography for
premenopausal women in their forties. Breast tissue is less radiographically
dense in the follicular phase than in the luteal phase.
PMID- 9637140
TI - Insulin-like growth factor 1 and prostate cancer risk: a population-based, case
control study.
AB - BACKGROUND: Recent epidemiologic investigations have suggested an association
between increased blood levels of insulin-like growth factor 1 (IGF-1) and
increased risk of prostate cancer. Our goal was to determine whether an
association exists between serum levels of IGF-1 and one of its binding proteins,
insulin-like growth factor-binding protein 3 (IGFBP-3), and prostate cancer risk.
METHODS: An immunoradiometric assay was used to quantify IGF-1 levels and IGFBP-3
levels in serum samples as part of a population-based, case-control study in
Sweden. The study population comprised 210 patients with newly diagnosed,
untreated prostate cancer and 224 frequency-matched control subjects. Data were
analyzed by use of unconditional logistic regression to calculate odds ratios
(ORs) and 95% confidence intervals (CIs). Reported P values are two-sided.
RESULTS: The mean serum IGF-1 level for case patients (158.4 ng/mL) was
significantly higher than that for control subjects (147.4 ng/mL) (P = .02);
corresponding mean serum IGFBP-3 levels were not significantly different between
case patients (2668 ng/mL) and control subjects (2518 ng/mL) (P =.09). We found a
moderately strong and statistically significant (P = .04) positive association
between serum levels of IGF-1 levels and risk of prostate cancer (OR = 1.51; 95%
CI = 1.0-2.26 per 100 ng/mL increment); the association was particularly strong
for men younger than 70 years of age (OR = 2.93; 95% CI = 1.43-5.97). No
association was found between serum IGF-1 levels and disease stage. Serum IGFBP-3
levels were not significantly associated with increased risk of disease, and
adjustment for IGFBP-3 had little effect on the association between IGF-1 levels
and risk of prostate cancer. CONCLUSION: Elevated serum IGF-1 levels may be an
important predictor of risk for prostate cancer. However, our results do not
support an important role for serum IGFBP-3 as a predictor of risk for this
disease.
PMID- 9637138
TI - Photodynamic therapy.
AB - Photodynamic therapy involves administration of a tumor-localizing
photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug),
followed by activation of the agent by light of a specific wavelength. This
therapy results in a sequence of photochemical and photobiologic processes that
cause irreversible photodamage to tumor tissues. Results from preclinical and
clinical studies conducted worldwide over a 25-year period have established
photodynamic therapy as a useful treatment approach for some cancers. Since 1993,
regulatory approval for photodynamic therapy involving use of a partially
purified, commercially available hematoporphyrin derivative compound (Photofrin)
in patients with early and advanced stage cancer of the lung, digestive tract,
and genitourinary tract has been obtained in Canada, The Netherlands, France,
Germany, Japan, and the United States. We have attempted to conduct and present a
comprehensive review of this rapidly expanding field. Mechanisms of subcellular
and tumor localization of photosensitizing agents, as well as of molecular,
cellular, and tumor responses associated with photodynamic therapy, are
discussed. Technical issues regarding light dosimetry are also considered.
PMID- 9637142
TI - Exposure to breast milk in infancy and adult breast cancer risk.
AB - BACKGROUND: There is considerable interest in the possibility of an infectious
etiology for human breast cancer. Although studies have shown that certain
strains of mice transmit mammary tumor virus via breast milk, few epidemiologic
studies have addressed this topic in humans. METHODS: We evaluated the
relationship between having been breast-fed as an infant and breast cancer risk
among 8299 women who participated in a population-based, case-control study of
breast cancer in women aged 50 years or more. Case women were identified through
cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin);
control women were identified through statewide driver's license lists (age <65
years) or Medicare lists (ages 65-79 years). Information on epidemiologic risk
factors was obtained through telephone interview. We used multiple logistic
regression to assess having been breast-fed and maternal history of breast cancer
in relation to breast cancer occurrence both in premenopausal women (205 case
women; 220 control women) and in postmenopausal women (3803 case women; 4071
control women). RESULTS: We found no evidence that having been breast-fed
increased breast cancer risk in either premenopausal women (odds ratio [OR] =
0.65; 95% confidence interval [CI] = 0.41-1.04) or postmenopausal women (OR =
0.95; 95% CI = 0.85-1.07). In addition, breast cancer risk was not increased by
having been breast-fed by a mother who later developed breast cancer. CONCLUSION:
Our results do not support the hypothesis that a transmissible agent in breast
milk increases breast cancer risk. Because premenopausal women were not well
represented in our study population, our findings with regard to this group may
not be generalizable and should be viewed with caution.
PMID- 9637141
TI - Association of p27Kip1 levels with recurrence and survival in patients with stage
C prostate carcinoma.
AB - BACKGROUND: There are few biologic determinants that are prognostic for patients
with localized prostate cancer. We examined whether cellular levels of the cyclin
kinase inhibitor p27Kip1 (also known as p27) in prostate tumors could be used to
predict progression of this disease. METHODS: Levels of p27 in tumor cell nuclei
were assessed by immunohistochemical analysis of tissue sections from the primary
tumors of 96 patients with stage C prostate carcinoma who had been treated by
radical prostatectomy. Tumors were classified into one of the following three
groups on the basis of the percentage of tumor cells showing nuclear p27
reactivity: low (0%-10%), moderate (11%-50%), and high (>50%). The Mantel
Haenszel test, Kaplan-Meier analysis, and the logrank test were used to calculate
the probability that nuclear p27 levels were associated with tumor grade and
substage, with a serum prostate-specific antigen (PSA) recurrence (defined as the
finding of a detectable level [0.4 ng/mL or greater] of serum PSA following
radical prostatectomy), with the recurrence of clinically evident disease, and
with survival. All reported P values are two-sided. RESULTS: Luminal cells and
basal cells of normal prostate glands showed high levels of nuclear p27
immunoreactivity in all tissue sections examined. Fifty-three tumors showed high
p27 reactivity, 31 showed moderate reactivity, and 12 showed low or no detectable
reactivity. Decreased levels of p27 were associated with tumor grade (P = .004).
Tumor levels of p27 were not associated with preoperative prostate-specific
antigen levels (P = .360) or with tumor substage (P = .320). However, decreased
p27 reactivity was significantly associated with an increased probability of
recurrence (P = .004) and decreased survival (P = .010). The median recurrence
free interval for patients with tumors showing high, moderate, or low p27
reactivity was 13.7 years, 8.4 years, and 4.7 years, respectively. Median
survival times were more than 14 years, more than 13.5 years, and 8.1 years for
patients in the high, moderate, and low p27 reactivity groups, respectively.
CONCLUSION: Levels of nuclear p27 immunoreactivity in the primary tumor can be
used to predict recurrence and survival among patients with localized prostate
cancer.
PMID- 9637143
TI - Short-term effects of population-based screening for prostate cancer on health
related quality of life.
AB - BACKGROUND: Population-based screening for prostate cancer is currently being
evaluated in randomized clinical trials in the United States and in Europe. Side
effects arising from the process of screening and from the earlier treatment of
screen-detected prostate cancer may be important factors in the evaluation. To
examine health-related quality of life (or health status) among men screened for
prostate cancer, we conducted a longitudinal study of 626 attenders to the
Rotterdam (The Netherlands) prostate cancer screening program and of 500
nonparticipants. METHODS: Attenders of the screening program and nonparticipants
completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36
Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health
related quality of life] health surveys) to measure generic health status, as
well as an additional questionnaire for anxiety and items relating to prostate
cancer screening. RESULTS: Physical discomfort during digital rectal examination
and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139
(29%) of 487 men, respectively; discomfort during prostate biopsy was reported by
64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the
participants did not experience relevant changes in physical, psychological, and
social functioning during the screening procedure. However, high levels of
anxiety were observed throughout the screening process among men with a high
predisposition to anxiety. Similar scores for anxiety predisposition were
observed among attenders and nonparticipants. CONCLUSIONS: At the group level, we
did not find evidence that prostate cancer screening induced important short-term
health-status effects, despite the short-lasting side effects related to the
biopsy procedure. However, subgroups may experience high levels of anxiety. The
implication is that unfavorable health-status effects of prostate cancer
screening occur mainly in the treatment phase.
PMID- 9637144
TI - Re: Long-term feeding of sodium saccharin to nonhuman primates: implications for
urinary tract cancer.
PMID- 9637145
TI - Blood supply of metastatic hepatic tumors: suggestions for improved delivery of
chemotherapeutic agents.
PMID- 9637146
TI - Re: Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal
cancers.
PMID- 9637147
TI - Re: A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal
Cancer Syndrome: meeting highlights and Bethesda Guidelines.
PMID- 9637148
TI - Practice management guidelines for trauma from the Eastern Association for the
Surgery of Trauma.
PMID- 9637149
TI - Neurogenic hypotension in patients with severe head injuries.
AB - OBJECTIVE: To examine the occurrence of hypotensive episodes in patients with
severe traumatic brain injuries that are not of hypovolemic origin and to
investigate possible neurogenic or iatrogenic causes of such episodes. METHODS:
We reviewed Traumatic Coma Data Bank (TCDB) records of the 248 patients with
early hypotension. We attempted to eliminate episodes related to hemorrhagic
hypovolemia by excluding patients with (1) extracranial injuries of Abbreviated
Injury Scale scores > 3 (n = 99, 40%); (2) postresuscitation hematocrit levels <
35% (n = 76, 30.6%); (3) hematocrit levels decreasing to < 35% during the first
24 hours after injury (n = 47, 19%); and (4) patients with conflicting data (n =
5, 2%). This left 21 patients (8.5%) without discernible extracranial causes for
their hypotension. RESULTS: Of these 21 patients, 4 had no extracranial injuries
and 4 had only a single injury with Abbreviated Injury Scale score = 1.
Hypotensive episodes were not associated with terminal or unsalvageable status.
Mortality was 43%. Of the multiple factors investigated, the only two that were
strongly associated with these "unexplained" hypotensive episodes were the
presence of a diffuse injury pattern on computed tomography (n = 15, 71%) and the
early use of mannitol or furosemide (n = 16, 76%) (It was policy at TCDB centers
that hypotensive patients not receive diuretics until they were resuscitated.)
CONCLUSIONS: (1) Some episodes of severe traumatic brain injury-related
hypotension may be of neurogenic origin. (2) The risk/benefit ratio of early
diuretic use in patients with severe traumatic brain injuries may be too high to
support liberal use. These data strongly support the need for a study involving
prospective collection of data describing the early blood pressure courses in
such patients.
PMID- 9637150
TI - A biomechanical strength comparison of external fixators.
AB - BACKGROUND: The purpose of this study was to biomechanically test the current
commercially available uniplanar, half-pin external fixators, comparing
stiffness, weight, and cost. METHODS: The Hammer, HexFix, Hoffmann, Monotube
Blue, Monotube Red, Torus, TraumaFix, and Ultra-X were tested using previously
published methods. The Instron 4500 was used to assess the strength
characteristics in axial, torsional, anteroposterior, and lateral bending of each
device. Weight was based on the unassembled fixator construct. Cost was
determined from the purchase price of each individual fixator. RESULTS: The
results of this study revealed that the Torus was the stiffest external fixator
tested in torsion. The Monotube Red was the stiffest in axial loading,
anteroposterior bending, and lateral bending. The Hammer and Hoffmann external
fixators were the heaviest constructs. The Torus and HexFix were the most
expensive. CONCLUSION: Many factors, including stiffness, weight, cost, ease of
application, fracture characteristics, and personal preference, go into deciding
which external fixator to use. The data presented compare stiffness
characteristics of several fixators under standardized loading conditions. These
data indicate that the Torus and Monotube Red provide the greatest stiffness when
comparing all modes of failure.
PMID- 9637151
TI - Long-term results of the external fixation of distal radius fractures.
AB - OBJECTIVE: To evaluate the long-term results of external fixation of distal
radius fractures. METHODS: A retrospective follow-up study (median follow-up, 5.3
years) of 49 patients with 50 distal radius fractures treated with an external
fixator was carried out. An external fixator (Minifixator, Stratec Medical,
Waldenburg, Switzerland) was used. The operative procedure is described in
detail. A personal evaluation including clinical and radiologic assessment of
both wrists was performed. RESULTS: The functional results, including the
parameters strength, daily activities, range of motion, and presence of pain, as
well as an anatomic score, the presence of osteoarthritis, the quality of
reduction, and complications were recorded. Functional and anatomic results
indicated excellent to good ratings in more than 80% of the cases. CONCLUSION:
The external fixator is a versatile tool in the treatment of intra-articular and
extra-articular fractures of the distal radius. The rate of algodystrophy (reflex
sympathetic dystrophy) was 6%, and wrist stiffness was not found in our series.
PMID- 9637152
TI - Timing fracture repair in patients with severe brain injury (Glasgow Coma Scale
score <9)
AB - BACKGROUND: Trauma patients with severe brain injury are at risk of secondary
brain injury. Femur fractures, if present, should be repaired when potential
causes of secondary brain injury have been corrected. METHODS: Sixty-one patients
with severe or moderate closed head injury and femur fractures were identified.
Patients were divided into groups by time until femur fracture reduction.
RESULTS: An inversely proportional trend was demonstrated when comparing time
until surgery with the percentage of patients who experienced hypotensive events
during surgery. Patients in the 0- to 2-hour group were eight times more likely
to become hypotensive during femur repair than patients in the >24-hour group.
Seventy-four percent of patients with intracranial pressure monitoring
experienced cerebral perfusion pressure <70 mm Hg. CONCLUSIONS: Operation in
similar patients should be done when risks are minimized by adequate
resuscitation. Secondary brain injury is more common in early femur repair.
Operation delay of 24 hours may be necessary to prevent hypoxia, hypotension, and
low cerebral perfusion pressure.
PMID- 9637153
TI - Emergency craniotomy in a rural Level III trauma center.
AB - Patients with closed head injury and expanding epidural (EDH) or subdural (SDH)
hematoma require urgent craniotomy for decompression and control of hemorrhage.
In remote areas where neurosurgeons are not available, trauma surgeons may
occasionally need to intervene to avert progressive neurologic injury and death.
In 1990, a young man with rapidly deteriorating neurologic signs underwent
emergency burr hole decompression of a combined EDH/SDH at our hospital, with
complete recovery. In anticipation of future need, five surgeons at our rural,
American College of Surgeons-verified Level III trauma center participated in a
neurosurgeon-directed course in emergency craniotomy. Since January 1, 1991, 792
patients have been entered into the trauma registry, including 60 with closed
head injury and Glasgow Coma Scale (GCS) score of 13 or less. All but seven were
transferred to a regional Level II trauma center, which is a minimum flight time
of 1 hour each way. All patients with EDH (5) and 2 of 14 with SDH were deemed
too unstable for transport and underwent burr hole decompression followed by
immediate transfer. All craniotomies were approved by the consulting neurosurgeon
and were done for computed tomography-confirmed lesions combined with neurologic
deterioration as demonstrated by (1) GCS score of 8 or less, (2) lateralizing
signs (dilated pupil, hemiparesis), or (3) development of combined bradycardia
and hypertension. One patient with a GCS score of 3 on arrival died. Seven
survivors (mean follow-up, 3.9 years; range, 1-6.5 years), including the index
case, function independently, although one survivor has moderate cognitive and
motor impairment. We conclude that early craniotomy for expanding epidural and
subdural hematomas by properly trained surgeons may save lives and reduce
morbidity in properly selected cases when timely access to a neurosurgeon is not
possible.
PMID- 9637154
TI - New diagnostic peritoneal lavage criteria for diagnosis of intestinal injury.
AB - BACKGROUND: Although diagnostic peritoneal lavage (DPL) is a well-established,
reliably objective method of diagnosis of intraperitoneal injury, it is too
sensitive to be used as an indicator for emergency celiotomy. Therefore, since
the development of ultrasonography and advanced computed tomographic scanners,
the role of DPL has been markedly reduced. Despite such remarkable advances,
however, radiologic diagnosis of intestinal injury cannot always provide
definitive results, and DPL may still be valuable in such instances. We have
developed a new DPL criteria specifically designed to aid in the diagnosis of
intestinal injury and have evaluated its effectiveness. METHODS: From August 1988
to December 1995, we performed DPL in 250 patients with blunt abdominal trauma
and analyzed the diagnostic accuracy of our new criteria. We used the standard
quantitative white blood cell (WBC) criterion for detection of intestinal injury
supplemented by a positive-negative borderline adjusted to WBC > or = red blood
cell (RBC)/150, where RBC > or = 10 x 10(4)/mm3. RESULTS: Our criteria had a
diagnostic sensitivity of 96.6% and a specificity of 99.4% for intestinal injury
after exclusion of 57 patients in whom DPL was performed within 3 hours or after
18 hours from the time of injury. In 133 patients with hemoperitoneum, emergency
celiotomy was performed in only 48; the remaining 85 patients with negative DPL
based on the WBC criterion avoided surgery, and conservative management resulted
in no complications. CONCLUSION: With the proposed criteria, DPL can be used to
diagnose or exclude intestinal injury even in the presence of hemoperitoneum.
PMID- 9637155
TI - Prospective evaluation of early missed injuries and the role of tertiary trauma
survey.
AB - BACKGROUND: This study prospectively evaluated the prevalence, clinical
significance, and contributing factors to early missed injuries and the role of
tertiary survey in minimizing frequency of missed injuries in admitted trauma
patients. Missed injury, clinically significant missed injury, tertiary survey,
and contributing factors were defined. Tertiary survey was conducted within 24
hours. RESULTS: Of 206 patients, 134 patients (65%) had 309 missed injuries
composing 39% of all 798 injuries seen. Tertiary trauma survey detected 56% of
early missed injuries and 90% of clinically significant missed injuries within 24
hours. Clinically significant missed injuries occurred in 30 patients with
complications in 11 patients and death in two patients. Of 224 contributing
errors, 123 errors were in clinical assessment, 83 errors were in radiology, 14
errors were patient related, and four errors were technical. The missed injury
rate was significantly higher in patients with multiple injuries and in those
involved in road crashes. CONCLUSIONS: Secondary trauma survey is not a
definitive assessment and should be supplemented by tertiary trauma survey.
PMID- 9637156
TI - Improved success in nonoperative management of blunt splenic injuries:
embolization of splenic artery pseudoaneurysms.
AB - OBJECTIVES: By using abdominal computed tomographic scans in the evaluation of
blunt splenic trauma, we previously identified the presence of vascular blush as
a predictor of failure, with a failure of nonoperative management of 13% in that
series. This finding led to an alteration in our management scheme, which now
includes the aggressive identification and embolization of splenic artery
pseudoaneurysms. METHODS: The medical records of 524 consecutive patients with
blunt splenic injury managed over a 4.5-year period were reviewed for the
following information: age, Injury Severity Score (ISS), American Association for
the Surgery of Trauma splenic injury grade (SIG), method and outcome of
management. RESULTS: Of the patients, 66% were male with a mean age of 32 +/- 16,
and mean ISS of 25 +/- 13. A total of 180 patients (34%) were managed with urgent
operation on admission (81% splenectomy (SIG 4.0), 19% splenorrhaphy (SIG 2.6)).
The remaining 344 patients (66%) were hemodynamically stable and underwent
computed tomographic scan and planned nonoperative management. Of these patients,
322 patients (94%) were successfully managed nonoperatively (61% of total splenic
injuries). In 26 patients (8%), a contrast blush identified on computed
tomographic scan was confirmed as a parenchymal pseudoaneurysm on arteriography.
Twenty patients (SIG, 2.8) were successfully embolized. In six patients,
technical failure precluded embolization; all required splenectomy (SIG, 4.0). A
total of 22 patients (6%) failed nonoperative management, including the six with
unsuccessful embolization attempts. Sixteen patients (SIG, 3.0) who had no
evidence of pseudoaneurysm were explored for a falling hematocrit, hemodynamic
instability, or a worsening follow-up computed tomography: 13 patients had
splenectomy, and three patients had splenorrhaphy. CONCLUSIONS: Aggressive
surveillance for and embolization of posttraumatic splenic artery pseudoaneurysms
improved the rate of successful nonoperative management of blunt splenic trauma
to 61%, with a nonoperative failure rate of only 6%. In comparison with our
previous work, this reduction in failure of nonoperative management is a
significant improvement (p < 0.03).
PMID- 9637157
TI - Intra-abdominal hypertension after life-threatening penetrating abdominal trauma:
prophylaxis, incidence, and clinical relevance to gastric mucosal pH and
abdominal compartment syndrome.
AB - OBJECTIVE: To define the incidence, prophylaxis, and treatment of intra-abdominal
hypertension (IAH) and its relevance to gut mucosal pH (pHi), multiorgan
dysfunction syndrome, and the abdominal compartment syndrome (ACS). METHODS:
Seventy patients in the SICU at a Level I trauma center (1992-1996) with life
threatening penetrating abdominal trauma had intra-abdominal pressure estimated
by bladder pressure. pHi was measured by gastric tonometry every 4 to 6 hours.
IAH (intra-abdominal pressure> 25 cm of H2O) was treated by bedside or operating
room laparotomy. RESULTS: Injury severity was comparable between patients who had
mesh closure as prophylaxis for IAH (n = 45) and those who had fascial suture (n
= 25). IAH was seen in 10 (22.2%) in the mesh group versus 13 (52%) in the
fascial suture group (p = 0.012) for an overall incidence of 32.9%. Forty-two
patients had pHi monitoring, and 11 of them had IAH. Of the 11 patients, eight
patients (72.7%) had acidotic pHi (7.10 +/- 0.2) with IAH without exhibiting the
classic signs of ACS. The pHi improved after abdominal decompression in six and
none developed ACS. Only two patients with IAH and low pHi went on to develop
ACS, despite abdominal decompression. Multiorgan dysfunction syndrome points and
death were less in patients without IAH than those with IAH and in patients who
had mesh closure. CONCLUSIONS: IAH is frequent after major abdominal trauma. It
may cause gut mucosal acidosis at lower bladder pressures, long before the onset
of clinical ACS. Uncorrected, it may lead to splanchnic hypoperfusion, ACS,
distant organ failure, and death. Prophylactic mesh closure of the abdomen may
facilitate the prevention and bedside treatment of IAH and reduce these
complications.
PMID- 9637158
TI - Alternatives in the management of penetrating injuries to the iliac vessels.
AB - BACKGROUND: The high mortality and morbidity rates after iliac vessel injuries
remain a challenging problem for trauma surgeons. Several controversial issues
surround the management of iliac vessel injuries, including the value of
abbreviated laparotomy, the role of extra-anatomic bypass reconstruction (EABR),
the use of vascular prostheses in the presence of contamination, and the need and
timing for fasciotomy. METHODS: Retrospective review of the records of patients
who sustained an injury to the iliac vessel between 1987 and 1996. RESULTS: A
total of 64 patients were treated, including 23 with isolated iliac vein
injuries, 17 with arterial injuries, and 24 with combined arteriovenous injuries.
Vascular prostheses were placed in 17 patients with arterial injuries, including
12 with associated intestinal wounds. Graft infection did not occur. Of the 24
patients with combined injuries, 11 underwent abbreviated laparotomy and 1 died.
Five deaths, however, occurred in 13 patients in whom no attempts were made for
damage control laparotomy. Significant differences between survivors and
nonsurvivors included final arterial pH, final prothrombin time, length of
hypotension, and number of transfusions. Arterial ligation with EABR was
performed in five patients and failed in two. Deep venous thrombosis and
pulmonary embolism occurred in four patients, in three of them after venous
injuries were ligated. The overall mortality rate was 23%. CONCLUSION: Our
findings show that (1) abbreviated laparotomy reduces mortality in iliac
injuries; (2) EABR should be performed early after stabilization to prevent limb
ischemia; (3) the use of vascular prostheses with associated intestinal injuries
did not appear to increase the incidence of graft infection; and (4) after vein
ligation, early fasciotomy and prophylaxis against extremity swelling, deep
venous thrombosis, and pulmonary embolism should be considered.
PMID- 9637159
TI - Intestinal permeability correlates with severity of injury in trauma patients.
AB - BACKGROUND: Increased intestinal permeability (IP) and the release of toxic
intraluminal materials have been implicated in the systemic inflammatory response
syndrome (SIRS) and multiple organ failure (MOF) observed in patients after
severe trauma. Previous studies of intestinal permeability have failed to
demonstrate a correlation between early measurements of IP and indicators of
injury severity. This study examines the relationship between standard measures
of injury severity and the early (day 1) and delayed (day 4) changes in IP.
Associations between IP and the development of SIRS, MOF, and infectious
complications were also studied. METHODS: The metabolically inactive markers
lactulose (L) and mannitol (M) were used to measure IP in 29 consecutive patients
who sustained injuries that required admission to the surgical intensive care
unit and in 10 healthy control subjects. Measurements were made within 24 hours
of admission and on hospital day 4. Severity of injury was assessed by A Severity
Characterization of Trauma (ASCOT), Trauma and Injury Severity Score (TRISS),
Injury Severity Score (ISS), Revised Trauma Score (RTS), and Acute Physiology and
Chronic Health Evaluation (APACHE) II score. Postinjury infections and parameters
of SIRS and MOF were recorded. RESULTS: The IP of healthy volunteers (L/M, 0.025
+/- 0.008) was within the normal range (L/M < or = 0.03), whereas the average IP
in injured patients was increased both within 24 hours (L/M, 0.139 +/- 0.172) and
on the fourth hospital day (L/M, 0.346 +/- 0.699). No significant correlation
between severity of injury and increased IP was seen within 24 hours of injury. A
significant correlation was seen on hospital day 4, however, with all severity
indices measured (ASCOT: r = 0.93, R2 = 0.87, p < 0.001; TRISS: r = 0.93, R2 =
0.87, p < 0.001; ISS: r = 0.84, R2 = 0.70, p < 0.001; RTS: r = 0.68, R2 = 0.47, p
= 0.002; APACHE II score: r = 0.51, R2 = 0.26, p = 0.04). Patients with markedly
increased IP (L/M > or = 0.100) experienced a significant increase in the
development of SIRS (83 vs. 44%; p = 0.03) and subsequent infectious
complications (58 vs. 13%; p = 0.01) and showed close correlation with the
multiple organ dysfunction scores (r = 0.87, R2 = 0.76, p < 0.001). CONCLUSION:
These observations demonstrate that the increased IP observed after trauma
correlates with severity of injury only after 72 to 96 hours and not within the
initial 24 hours of injury. A large increase in IP is associated with the
development of SIRS, multiple organ dysfunction, and an increased incidence of
infectious complications.
PMID- 9637160
TI - Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma
anergy.
AB - BACKGROUND: We have previously shown that an intrinsic postinjury T-cell
dysfunction defined as lack of proliferative response to direct stimulation
through the T-cell receptor, referred to here as "anergy," occurs in a subgroup
of patients with severe trauma and is associated with organ failure. It has been
suggested recently that a dominance of T-helper-2 (Th2) lymphokine production
might be responsible for immunosuppression and associated with poor patient
outcome. Here, we hypothesize that anergy is associated with global failure of T
lymphokine (T LK) production, suggesting that poor outcome is not the result of
an excess of immunosuppressive T LK (i.e., interleukin (IL)-10) but rather
results from lost T-cell regulatory networking. METHODS: Purified T cells from 37
severely injured trauma patients were cultured and stimulated with
alphaCD3/alphaCD4, and proliferation was assessed at 72 hours. Anergy is defined
as occurring when the patient's T-cell proliferation to alphaCD3/alphaCD4 is less
than 50% of the simultaneously run normal proliferation. Culture supernatants
were assessed for T LK production by enzyme-linked immunosorbent assay. Clinical
severity was measured by the multiple organ dysfunction syndrome (MODS) and Acute
Physiology and Chronic Health Evaluation III scores. RESULTS: Anergy occurred in
20 of 37 patients, and it usually appeared at greater than 5 to 7 days after
injury. There was a global reduction of T LK production during T-cell anergy (IL
2, 2.5%; interferon (IFN)gamma, 30.5%; IL-4, 11.8%; and IL-10, 16.9%) compared
with increased or unchanged T LK production during the nonanergic state (IL-2,
83%; IFNgamma, 230%; IL-4, 110%; and IL-10, 307.9%; p < 0.01). There was a
significant direct correlation between depressed IL-4 and depressed IFNgamma (r =
0.620, p < 0.001), indicating a diminished LK production of both types of T
helper cells (Th1 and Th2). Decreased IL-2 and IL-10 levels were also
specifically correlated to each other during the anergic state (r = 0.91, p <
0.001). The average MODS score for patients during anergy was significantly
higher (7.6) than their MODS score in the absence of anergy (4.0, p = 0.01). When
IL-2 and IL-10 were measured simultaneously, a predominance of Th2 LK (IL-10)
production would result in an IL-10/IL-2 ratio greater than 1. We found, however,
that this ratio was not greater than 1 in 80% of assays in which T cells were
anergic (p = 0.01). CONCLUSION: During T-cell anergy there is not a predominance
of Th2 lymphokine production but rather a global depression of the T-cell
lymphokine profile. Both depressed T-cell proliferation and depressed LK
production correlate to poor clinical outcome.
PMID- 9637161
TI - Recombinant human granulocyte colony-stimulating factor attenuates inflammatory
responses in septic patients with neutropenia.
AB - OBJECTIVE: The objective of this study was to determine the effects of
recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration
in septic patients with neutropenia. METHODS: Twenty consecutive septic patients
were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days
(group G). They were compared with 14 septic patients treated earlier without rhG
CSF (group N). All patients in both groups met the criteria of total leukocyte
count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL.
Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI),
Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's
Multiple Organ Failure (MOF) index were evaluated. In addition, nucleated cell
count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and
bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as
inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an
indicator of the tissue injury were evaluated in group G. RESULTS: In group G,
TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL
6, and IL-8 decreased reciprocally. There was no deterioration of LE and RI.
Consequently, the APACHE II score and MOF index improved. In group N, however,
CRP showed no change concomitant with the APACHE II score and MOF index.
CONCLUSION: Administration of rhG-CSF attenuates inflammatory responses without
inducing tissue injury in septic patients with neutropenia.
PMID- 9637162
TI - Changes of the interleukin-6 levels in skin at different sites after thermal
injury.
AB - OBJECTIVE: To delineate the regulation of IL-6 production in unburned skin
adjacent to a burn in an animal model. METHODS: In C57BL/6 mice, at 15, 30, and
60 minutes after a 20% full-thickness burn, skin was removed from various sites.
Control samples were obtained from unburned mice. Normal skins were incubated
with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), IL
1 beta, and IL-6. Unburned skin specimens were incubated with anti-TNF-alpha and
IL-1alpha antibodies. Cytokine levels were measured by enzyme-linked
immunosorbent assay. RESULTS: The burn increased the IL-6 levels at 30 minutes (p
< 0.05) and the IL-1alpha levels at 15 and 60 minutes in the unburned skin. TNF
alpha, IL-1alpha, and IL-1beta increased IL-6 production in normal skin (p <
0.05). Anti-IL-1alpha antibody decreased IL-6 production in the unburned skin (p
< 0.05). CONCLUSIONS: IL-1alpha modulates IL-6 production in unburned skin after
injury. IL-6 and IL-1alpha might contribute to the alterations after a burn.
PMID- 9637163
TI - Imprecision in lower "inflection point" estimation from static pressure-volume
curves in patients at risk for acute respiratory distress syndrome.
AB - BACKGROUND: Static pressure-volume (PV) curves have been promoted as a tool for
selecting positive end-expiratory pressure (PEEP) by identifying a lower
"inflection point" (Pflex) from these curves. Their visual interpretation is
subjective and difficult, however, particularly with subtle changes in the slope
of the curves. This study was designed to examine the physician-to-physician
variability in estimating the lower Pflex from these curves. METHODS: Static PV
curves for eight patients were obtained within 24 hours of admission. Five
intensivists and one respiratory therapist independently estimated the lower
Pflex from these curves. RESULTS: Pflex estimates for individual patients were
highly variable, ranging from 5 to 9 cm H2O. This variability was not
attributable to a single discordant estimate, nor was a single physician
responsible for consistently high or low estimates. CONCLUSION: Static PV curve
interpretation with current methods imprecisely estimates the lower inflection
point and is of limited usefulness in PEEP selection.
PMID- 9637164
TI - Significance of peritoneal fluid as an isolated finding on abdominal computed
tomographic scans in pediatric trauma patients.
AB - BACKGROUND: Peritoneal fluid on abdominal computed tomographic (CT) scan in the
absence of solid-organ injury suggests a bowel injury. We sought to determine the
significance of peritoneal fluid as the sole finding on abdominal CT scans
obtained to evaluate injured pediatric patients. METHODS: We performed a
retrospective review of abdominal CT scans obtained during the initial survey of
blunt trauma patients less than 19 years old during a 5-year period (1991-1995).
All patients received intravenous and oral contrast agents. All CT scans were
read by a staff radiologist. All CT scan results were retrospectively verified by
one of the authors. RESULTS: Of the 259 scans, 157 (59%) were read as normal; 76
(31%) demonstrated solid-organ injury or pelvic fracture; 2 (1%) had
pneumoperitoneum and 24 (9%) had peritoneal fluid as the only finding.
Quantification of the fluid was done using a previously described method. Of the
16 patients with a small amount of fluid, only 2 (12%) required celiotomy. Of the
eight patients with a moderate amount of fluid, four (50%) required celiotomy. At
celiotomy, the six patients all had small-bowel injuries. No abdominal CT scan
demonstrated extravasation of oral contrast. CONCLUSION: Intra-abdominal fluid as
the sole finding on abdominal CT scan does not mandate immediate celiotomy in the
bluntly injured pediatric patient. The patient with fluid in more than one
location has a 50% chance of bowel injury. We also conclude that extravasated
enteral contrast is rarely present to aid in the diagnosis of bowel injury in
children.
PMID- 9637165
TI - One hundred five penetrating cardiac injuries: a 2-year prospective evaluation.
AB - OBJECTIVES: To analyze the parameters measured in the field, during transport,
and upon arrival of the physiologic condition of patients sustaining penetrating
cardiac injuries, along with the Cardiovascular Respiratory Score (CVRS)
component of the Trauma Score, the mechanism and anatomical site of injury,
operative characteristics, and cardiac rhythm as predictors of outcome. We also
set out to identify a set of patient characteristics that best predict mortality
outcome and to correlate cardiac injury grade as determined by the American
Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) with
mortality. METHODS: This report was a prospective study at American College of
Surgeons Level I urban trauma center. Interventions included thoracotomy,
sternotomy, or both, for resuscitation and definitive repair of cardiac injury.
The main outcome measures used were those parameters measuring physiologic
condition of patients, CVRS, mechanism and anatomical site of injury, mortality,
and grade of injury. RESULTS: A total of 105 patients sustained penetrating
cardiac injuries: 68 injuries (65%) were gunshot wounds and 37 injuries (35%)
were stab wounds. The mean Injury Severity Score was 36. Of the 105 wounds, 23
wounds (22%) involved multiple-chamber injuries. The overall survival was 35 of
105 patients (33%): survival of gunshot wound victims was 11 of 68 patients
(16%); survival of stab wound victims was 24 of 37 patients (65%). Emergency
department thoracotomy was performed in 71 of the 105 patients (68%) with 10
survivors (14%). CVRS: 94% mortality (50 of 53) when CVRS = 0, 89% mortality (57
of 64) when CVRS = 0 to 3, and 31% mortality (12 of 39) when CVRS 4 to 11 (p <
0.001). The presence of sinus rhythm when pericardium was opened predicted
survival (p < 0.001). Anatomical site of injury (injured chamber) and the
presence of tamponade did not predict survival. Stepwise logistic regression
analysis identified gunshot wound, exsanguination, and restoration of blood
pressure as most predictive variables of mortality. AAST-OIS injury grade and
mortality: grade I, 0 of 1 (0%); grade II, 1 of 2 (50%); grade III, 2 of 3 (66%);
grade IV, 28 of 50 (56%); grade V, 29 of 38 (76%); grade VI, 10 of 11 (91%).
Overall incidence: grades IV-VI, 99 of 105 (94%). CONCLUSIONS: Parameters
measuring physiologic condition, CVRS, and mechanism of injury are significant
predictors of outcome in penetrating cardiac injuries. AAST-OIS injury grades I
III are rare in penetrating cardiac trauma. AAST-OIS Injury grades IV-VI are
common in penetrating cardiac trauma and accurately predict outcome.
PMID- 9637166
TI - Lingual trauma: the use of medicinal leeches in the treatment of massive lingual
hematoma.
PMID- 9637167
TI - Esophageal injury secondary to thoracic spinal trauma: the need for early
diagnosis and aggressive surgical treatment.
PMID- 9637168
TI - Primary enucleation as a consequence of airbag injury.
PMID- 9637169
TI - Tension colothorax: a pleural effusion?
PMID- 9637170
TI - Stent graft of a traumatic vertebral artery injury: case report.
PMID- 9637171
TI - Bilateral calcaneal fracture in a child treated by percutaneous reduction and
screw fixation.
PMID- 9637172
TI - Entrapment and transection of the median nerve associated with greenstick
fractures of the forearm: case report and review of the literature.
AB - OBJECTIVE: To report an unusual neurologic complication associated with
greenstick fractures of the forearm. METHODS: Near-complete transection of the
median nerve associated with greenstick fractures of the shaft of the left radius
and ulna in a 13-year-old boy is described. The results of treatment are reported
in detail. CONCLUSION: Significant median nerve injury may coexist with
apparently benign, closed greenstick fractures of the forearm.
PMID- 9637173
TI - Bone transport combined with free flap reconstruction and antibiotic bead spacers
for a type IIIB open tibial fracture: case report.
PMID- 9637174
TI - Neurologic dysfunction in the multiple organ dysfunction syndrome.
PMID- 9637175
TI - A golden opportunity.
PMID- 9637176
TI - The overall impact of air transport on trauma outcome.
PMID- 9637177
TI - Closed humeral shaft fractures: a prospective evaluation of surgical treatment.
PMID- 9637178
TI - Morbidity in 624 patients requiring prehospital chest tube decompression.
PMID- 9637179
TI - Functional and adaptive significance of primate pads and claws: evidence from New
World anthropoids.
AB - This study tests predicted morphoclines in fingertip morphology among four small
bodied (<1 kg) New World monkeys (Saimiri sciureus, Leontopithecus rosalia,
Callithrix jacchus, and Saguinus oedipus) in order to test previous functional
and adaptive explanations for the evolution of flattened nails, expanded apical
pads, and grasping extremities within the Order Primates. Small-bodied
platyrrhines which frequently forage among small-diameter substrates are expected
to possess 1) relatively expanded apical pads, 2) well-developed epidermal
ridges, 3) distally broad terminal phalanges, and 4) reduced flexor and extensor
tubercles compared to those species which use large-diameter arboreal supports
more frequently for their locomotor and postural behaviors. Results show that as
the frequency of small-branch foraging increases among taxa within this sample,
relative distal phalanx breadth also increases but distal phalanx length, height,
and flexor tubercle size decrease. Moreover, epidermal ridge development becomes
more pronounced as the frequency of small-branch foraging increases. Terminal
phalanx breadth and epidermal ridge complexity are both positively correlated
with apical pad size. The large, flexible apical pad increases stability of the
hand and foot on small-diameter arboreal supports because the pad can contact the
substrate in several planes which, in turn, enables the pad to resist disruptive
forces from different directions by friction and interlocking (Hildebrand, 1995).
The observed morphoclines demonstrate that a gradient in form from claw- to nail
like tegulae exists among these taxa. Thus, the distinction between claw- and
nail-bearing platyrrhines is essentially arbitrary. These observations
corroborate Cartmill's (1972) functional and adaptive model for the loss of claws
in primates: namely, expanded apical pads are required for habitual locomotor and
postural behaviors on small-diameter supports whereas claws are more useful for
positional behaviors on large-diameter substrates. Finally, results from this
study support previous suggestions that the keeled tegulae of callitrichines
represent a derived postural adaptation rather than a primitive retention from an
ancestral eutherian condition.
PMID- 9637180
TI - Limbic frontal cortex in hominoids: a comparative study of area 13.
AB - The limbic frontal cortex forms part of the neural substrate responsible for
emotional reactions to social stimuli. Area 13 is one of the cortical areas long
known to be part of the posterior orbitofrontal cortex in several monkey species,
such as the macaque. Its presence nevertheless in the human brain has been
unclear, and the cortex of the frontal lobe of the great and lesser apes remains
largely unknown. In this study area 13 was identified in human, chimpanzee,
bonobo, gorilla, orangutan, and gibbon brains, and cortical maps were generated
on the basis of its cytoarchitecture. Imaging techniques were used to
characterize and quantify the microstructural organization of the area, and
stereological tools were applied for estimates of the volume of area 13 in all
species. Area 13 is conservative in its structure, and features such as size of
cortical layers, density of neurons, and space available for connections are
similar across hominoids with only subtle differences present. In contrast to the
homogeneity found in its organization, variation is present in the relative size
of this cortical area (as a percentage of total brain volume). The human and the
bonobo include a complex orbitofrontal cortex and a relatively smaller area 13.
On the contrary the orangutan stands out by having a shorter orbitofrontal region
and a more expanded area 13. Differences in the organization and size of
individual cortical areas involved in emotional reactions and social behavior can
be related to behavioral specializations of each hominoid and to the evolution of
emotions in hominids.
PMID- 9637181
TI - Second metacarpal midshaft geometry in an historic cemetery sample.
AB - Study of bone mass at the second metacarpal midshaft has contributed to our
understanding of skeletal growth and aging within and between populations and has
relied extensively on noninvasive techniques and in particular radiogrammetric
data. This study reports age, sex, and side variation in size and shape data
acquired from direct measurement of cross-sections obtained from a large (n =
356), homogeneous skeletal sample. Correlation analysis and three-way ANOVA of
size-adjusted data confirm general impressions of patterned variation in this
element: males have absolutely but not necessarily relatively larger bones than
females; the right side is larger than the left, though a larger than expected
proportion (approximately 25%) of left metacarpals exhibits greater values than
the right; and bone mass but not strength (in males) declines with age. Contrary
to the widely accepted assumption of circularity for this location, direct
measurement of cross-sectional geometry confirms previous biplanar
radiogrammetric conclusions regarding the noncircularity of the second metacarpal
midshaft and identifies a significant difference between males and females, with
the latter having a more cylindrical diaphysis. Deviation of the axes of maximum
and minimum bending strength associated with noncircularity suggests a
distribution of bone mass to resist bending moments perpendicular to the distal
palmar arch, though this conclusion awaits more robust study of the functional
anatomy of the metacarpal diaphysis.
PMID- 9637182
TI - Functional dental correlates of food properties in five Malagasy lemur species.
AB - Biomechanical explanations are fundamental to studies of functional dental
morphology. Until recently foods were not classified in mechanical categories
amenable to a rigorous examination of the fundamental physical relationship
between teeth and foods. Fruit, insect and leaf categories, although descriptive,
are mechanically heterogeneous. The diets of five Malagasy lemur taxa were
described in terms of two mechanical properties, hardness and shear strength, in
an earlier study (Yamashita, 1996b). In the present study, correlations between
these two physical food properties and second molar tooth features of two lemur
families are examined. Several relationships are hypothesized: 1) crest length is
expected to be positively correlated with food shear strength; 2) the radius of
curvature (r) of cusps is expected to be positively correlated with food
hardness; and 3) basin area should increase relative to cusp radius as food
hardness increases, and cusp-to-basin ratios should decrease with increasing food
hardness. Two additional hypotheses address the debate concerning the relative
influences of the most frequently eaten foods versus the most stressful foods in
determining tooth form. The results of the predicted relationships are equivocal.
1) Crest length is negatively instead of positively correlated with strong foods.
Crest lengths are correlated with quantities of leaf consumption, which are
related to leaf shape more than to material composition. 2) As expected, r is
positively correlated with food hardness and negatively with shear strength, but
this applies to upper molar cusps only. Lower molar cusps complicate simple
generalizations of relationships. 3) Hard foods are correlated with a tight fit
of occluding cusps and basins instead of the expected loose fit. The most
stressful foods eaten (hardest and strongest) have higher correlations with tooth
features than the most frequently eaten foods. Several functional complexes can
be identified. Hard food items are correlated with short cusps in lemurids, tight
occlusal fit, small trigon and large talonid areas, and deep, acute basins.
Large, shallow trigons, shallow, unrestricted talonids, and large upper molar
basins are indicative of a diet of strong foods. These results demonstrate that
some variation in tooth features is explicable with reference to mechanical
properties of diet, although the relationships are complex.
PMID- 9637183
TI - Evolution of the dentition in prehistoric Ohio Valley Native Americans: II.
Morphology of the deciduous dentition.
AB - In order to evaluate the microevolutionary dynamics of morphological features of
the deciduous dentition, I collected data on the variation of 57 features (33
crown and 24 root) from prehistoric Ohio Valley populations. I sampled a total of
370 individuals from 26 populations representing a lineage that inhabited the
middle and upper Ohio valley region from approximately 3000 to 350 BP.
Evolutionary changes in the frequencies of morphological features of the
deciduous teeth in this lineage were limited. Over 80% of the features show no
significant differences among the populations. The relatively few features that
show consistent differences separate pre- and postmaize agricultural populations.
I discuss explanations for this change in terms of selection differences or gene
flow. The general pattern of morphological trait expression in the deciduous
teeth of this Ohio Valley lineage corresponds to what has been termed the
Mongoloid dental complex (sinodonty in the permanent teeth). I suggest additional
features that, with further study, may be added to this morphological complex.
PMID- 9637184
TI - Dorset and Thule divergence from East Central Asian roots.
AB - The history of the immigration of East Asians to America during the last glacial
period remains controversial. In an attempt to add critical data to this problem,
a large sample of whole teeth derived from Southeast Asian, Mongolian, Thule,
Western Inuit, and pre-Inca (Huari) people was quantified (N = 4,507 teeth from
495 individuals; approximately 30 variables per tooth). Multivariate analysis
helped establish that all Native Americans were likely derived from one ancient,
extinct population that resided in the region of Mongolia (east Central Asia),
and that Mongolians and Southeast Asians are two independent groups. A
controversial and enigmatic Central Canadian Arctic "Thule culture Inuit" group
on Southampton Island that survived until 1902 was identified as a relic, mainly
Paleoeskimo Dorset community. Surprisingly, there was little, or no, indication
of Dorset-to-Thule gene flow. Cumulatively, the data suggest that a small
population of Paleoindian founders remained resident in Beringia, may have
blocked further immigration, and were the antecedents to the Thule/Inuit. With
the confluence of the Arctic and Pacific oceans at the breakup of Beringia, the
resulting increased availability of marine animal food sources allowed this
population to increase in size and expand throughout the eastern Arctic.
PMID- 9637185
TI - Variability in osteon size in recent human populations.
AB - The possibility of smaller osteons in the cortical bone of Late Pleistocene human
populations begs the question of how these histological features vary within
individual skeletons among and between populations. The distributional
characteristics of total osteon area (On.Ar) and Haversian canal area (H.Ar) are
explored using data from three samples of historically known individuals: ribs
and femora from eighteenth-century Huguenots in England (Spitalfields, n = 20),
ribs and femora from nineteenth-century British settlers in Canada (St. Thomas, n
= 21), and ribs from twentieth-century South African cadavers (University of Cape
Town; following curatorial classifications, n = 10 white, 10 black, 10 colored).
Neither histological variable is normally distributed. About 96% of the random
variation is within the individual bone sample. There are no significant
differences between sexes for either variable in any sample, and age has no
effect in most instances. Femoral osteons are significantly larger than rib
osteons within individuals and across samples. Haversian canal area is more
variable than On.Ar, especially in the twentieth-century sample, where within
sample coefficients of variation are frequently >100%. Using modern centiles
developed here, some Late Pleistocene long bone samples have On.Ar values below
the range of modern variation. Because of ribs' smaller cross-sectional areas and
less broadly ranging values for On.Ar, ribs would provide a preferable site for
future comparative studies.
PMID- 9637186
TI - Prehistoric juvenile rheumatoid arthritis in a precontact Louisiana native
population reconsidered.
AB - Descriptions of skeletal pathological conditions evident in the prehistoric
Tchefuncte adolescent 16ST1-14883b are clarified. The basis is reaffirmed for
assigning to the described pathological conditions a diagnostic perspective of
juvenile rheumatoid arthritis or juvenile Lyme disease--a disease that mimics
juvenile rheumatoid arthritis in its arthritic presentation--rather than of
assigning them as representative of juvenile onset ankylosing spondylitis or
other juvenile spondyloarthropathies. A hypothesis (Lewis [1994] Am. J. Phys.
Anthropol. 93:455-475) is restated that 1) the spirochete Borrelia burgdorferi
was the infectious agent responsible for prevalence of adult rheumatoid arthritis
in prehistoric southeastern Native American populations, 2) that B. burgdorferi
is a possible cause of the arthritis evident in individual 16ST1-14883b, and 3)
that antibodies to B. burgdorferi provided partial immunity to the related
spirochete Treponema pallidum for the 16ST1 precontact Tchefuncte population from
Louisiana, protecting them from severe treponemal response. Given the probable
widespread existence of Ixodid tick vectors for B. burgdorferi in prehistoric
North America, coupled with the existence of treponematosis, it follows that the
transition of Native American hunting-gathering economies to more sedentary
economies would predictably be linked to an increased incidence of treponematosis
due to the loss of benefits of the above-stated partial immunity. In other words,
as prehistoric Native American exposure to tick vectors for B. burgdorferi
decreased, susceptibility to treponematosis increased. Inferences regarding
biological controls interacting with and influencing prehistoric Native American
migration patterns are suggested from the link of B. burgdorferi to an Ixodid
tick common to northeast Asia.
PMID- 9637187
TI - Variation in epinephrine and cortisol excretion rates associated with behavior in
an Australian Aboriginal community.
AB - Urinary epinephrine and cortisol hormone output in a remote Australian Aboriginal
community was on average about twice as high in those individuals measured on a
Thursday or Friday as those measured at the beginning of the next week (Monday or
Tuesday). Diastolic blood pressure was about 6 mm Hg higher in the Thursday
Friday group, but the difference in mean systolic blood pressure between the day
groups does not reach statistical significance. These physiological differences
are associated with a marked dichotomy in behavior in the two time periods: on
the first 2 days, virtually all adults were involved in intense gambling activity
for large stakes, but this was not a feature of the latter period. This behavior
pattern occurs on a regular weekly basis. If substantiated by longitudinal
studies, this phenomenon may provide an additional link between human behavior
and a poor health profile mediated via the physiological consequences of high
stress hormone output.
PMID- 9637188
TI - Brief communication: gender and sex: vive la difference.
AB - The distinction prevalent in the social sciences between the terms sex and gender
is a useful one and ought to be preserved. Sex refers to the anatomical or
chromosomal categories of male and female. Gender refers to socially constructed
roles that are related to sex distinctions. Use of these terms as synonyms is
becoming increasingly frequent in physical anthropology, especially among
bioarchaeologists and primatologists. A failure to make the distinction between
gender and sex is analytically incapacitating in a field such as physical
anthropology, whose strength lies in the integration of biological and cultural
information.
PMID- 9637189
TI - The effects of caffeine on the maximal accumulated oxygen deficit and short-term
running performance.
AB - The purpose of this study was to evaluate the effect of acute caffeine ingestion
on the maximal accumulated oxygen deficit (MAOD) and short-term running
performance. Nine well-trained males performed a preliminary assessment and, at
least 4 days later, a supramaximal run to exhaustion. Their VO2max values were
determined, and the MAOD test at an exercise intensity equivalent to 125% VO2max
was performed. Caffeine (5 mg x kg(-1)) or placebo was administered 1 hr prior to
the MAOD in a double-blind, randomized cross-over study. In comparison to the
placebo condition, subjects in the caffeine condition developed a significantly
greater MAOD and increased their run time to exhaustion. However, post-MAOD blood
lactate concentration ([HLa]) was not different between trials for caffeine and
placebo. Caffeine ingestion can be an effective ergogenic aid for short-term,
supramaximal running performance and can increase MAOD. However, these results do
not appear to be related to an increased [HLa].
PMID- 9637190
TI - Vitamin E concentration in rat skeletal muscle and liver after exercise.
AB - The purpose of this study was to determine whether submaximal exercise
significantly changes the concentration of vitamin E (alphaToc) in rat liver and
skeletal muscle and to establish a time course for the return to basal levels.
Male Sprague-Dawley rats, age 8 to 10 weeks, were randomly divided into sedentary
control (Con) (n = 7) and exercise (n = 17) groups. Exercised animals ran 100 min
on a motorized treadmill at approximately 70% VO2max for 3 consecutive days. They
were then sacrificed immediately postexercise (0Post), 24 hr post (24Post), or 72
hr post (72Post). The gastrocnemius, red vastus lateralis (RV), white vastus
lateralis (WV), and liver were excised and analyzed for alphaToc concentration by
high-performance liquid chromotography utilizing electrochemical detection. We
found that after 3 consecutive days of exercise, alphaToc was reduced in RV and
WV at 0Post and 24Post but returned to control values by 72Post. Liver alphaToc
content was not changed at 0Post but was significantly reduced at 24Post and
72Post. No significant changes in alphaToc were observed in the gastrocnemius in
response to exercise. The data indicate that following an exercise-related
decrease, skeletal muscle vitamin E concentration requires more than 24 hr to
return to the preexercise concentration, and that the replenishment process may
involve redistribution of vitamin E from liver to muscle.
PMID- 9637191
TI - Body composition and nutritional assessments in soccer.
AB - This review summarizes results from studies investigating the physical
characteristics, daily energy expenditures, diets, and effects of nutritional
supplements to the habitual diets of soccer players. The results show that
players fall within a wide range of stature and body weight, and they are
classified as mesomorphs. The body fat of male players is about 10% of body
weight, whereas the average for females is about 21%. Energy expenditure for
males is about 4,000 kcal on training days and 3,800 kcal on match day, while
energy intake reported in other studies is on the order of 3,700 kcal.
Carbohydrate (CHO), fat, and protein intakes are about 53, 30, and 14% of energy
intake, respectively, the remaining being from alcohol intake. There are
indications that CHO supplements might be beneficial during soccer performance.
However, more research is needed to clarify the importance of branched-chain
amino acid and creatine supplementation in soccer.
PMID- 9637192
TI - Nutrition, exercise, and bone status in youth.
AB - The maximal amount of bone mass gained during growth (peak bone mass) is an
important determinant of bone mass in later life and thereby an important
determinant of fracture risk. Although genetic factors appear to be primary
determinants of peak bone mass, environmental factors such as physical activity
and nutrition also contribute. In this article, bone growth and maintenance are
reviewed, and mechanisms are described whereby physical activity can affect bone
mass. Studies addressing the effects of physical activity on bone status in youth
are reviewed: Although conclusive data are not yet available, considerable
evidence supports the importance of activity, especially activity initiated
before puberty. The critical role of energy in bone growth is outlined, and
studies assessing the impact of calcium intake during childhood and adolescence
are reviewed. Although results of intervention trials are equivocal, other
evidence supports a role for calcium intake during growth. Recommendations for
physical activity and nutrition, directed to children and adolescents, are
presented.
PMID- 9637193
TI - Resistance training and energy balance.
AB - In this brief review we examine the effects of resistance training on energy
expenditure. The components of daily energy expenditure are described, and
methods of measuring daily energy expenditure are discussed. Cross-sectional and
exercise intervention studies are examined with respect to their effects on
resting metabolic rate, physical activity energy expenditure, postexercise oxygen
consumption, and substrate oxidation in younger and older individuals. Evidence
is presented to suggest that although resistance training may elevate resting
metabolic rate, it does not substantially enhance daily energy expenditure in
free-living individuals. Several studies indicate that intense resistance
exercise increases postexercise oxygen consumption and shifts substrate oxidation
toward a greater reliance on fat oxidation. Preliminary evidence suggests that
although resistance training increases muscular strength and endurance, its
effects on energy balance and regulation of body weight appear to be primarily
mediated by its effects on body composition (e.g., increasing fat-free mass)
rather than by the direct energy costs of the resistance exercise.
PMID- 9637194
TI - Energy balance in young athletes.
AB - Very little is known about the energy needs of young athletes. Recent studies
using the doubly labeled water method have shown that the recommended dietary
allowances for energy may be too high for normally active children and
adolescents living in affluent societies. No studies of energy balance in young
athletes have been published. Self-report dietary records of young athletes
indicate that energy, carbohydrate, and select micronutrient intakes of certain
athletic groups and individual athletes may be marginal or inadequate. Potential
consequences of inadequate energy and nutrient intakes in young athletes include
poor bone health, fatigue, limited recovery from injuries, menstrual dysfunction
in female athletes, and poor performance. Studies of energy balance and nutrient
status in young athletes are needed to better understand the nutritional needs of
this group.
PMID- 9637195
TI - Effective fluid replacement.
AB - As a result of exercise-induced sweating, athletes and trained individuals can
lose up to 3 L of fluid per hour. Fluid replacement is required to maintain
hydration and allow the athlete to continue to perform. Inadequate fluid intake
will adversely affect temperature regulation, cardiovascular function, and muscle
metabolism. To maximize fluid intake and effectively replace fluid, athletes must
employ behavioral strategies. Athletes can also select beverages with
characteristics that complement their behavioral efforts. Palatability, rapid
absorption, retention of the fluid, and ergogenicity are the major attributes to
consider for enhancing hydration during training and physical activity.
PMID- 9637196
TI - An advertising campaign designed to sell videotapes for an exercise regimen
called the Campitelli Advanced 10-Minute Speed Exercise Method.
PMID- 9637197
TI - Laminin-alpha2 (merosin), beta-dystroglycan, alpha-sarcoglycan (adhalin), and
dystrophin expression in congenital muscular dystrophies: an immunohistochemical
study.
AB - Muscle biopsies of 13 congenital muscular dystrophy (CMD) patients were
investigated for the expression of laminin-alpha2 (merosin), beta-dystroglycan,
alpha-sarcoglycan (adhalin) and dystrophin. Expression of these proteins was
normal in six out of eight patients with pure-CMD, in three non-Japanese patients
clinically resembling Fukuyama-CMD (F-CMD), and in two patients with Walker
Warburg syndrome (WWS). The two 'pure'-CMD patients with white matter hypodensity
showed severely decreased laminin-alpha2 expression and normal expression of the
other proteins. Our findings in the non-Japanese patients, clinically resembling
F-CMD, are different from those in Japanese cases with F-CMD in the literature.
Consequently, our patients suffer from WWS or from another yet undetermined form
of CMD.
PMID- 9637198
TI - Postoperative intracranial abscess--clinical aspects in the differential
diagnosis to early recurrence of malignant glioma.
AB - Out of 2941 patients who received a clean, major craniotomy, 39 patients (1.3%)
developed the complication of an intracranial deep infection, i.e. abscess or
empyema. A total of 14 patients with a postoperative abscess were initially
operated upon intracerebral malignant glioma (WHO III or IV) and could be
compared to a matched group of patients with recurrent malignancy concerning
clinical and radiological aspects. A statistically significant elevation of
median values was seen for erythrocyte sedimentation rate (ESR), fibrinogen and
body temperature in the study group. C-reactive protein (CRP) was not
investigated in the control group and could not be compared, but it was elevated
in all abscess patients when measured. CT-scan did not allow a safe
differentiation between infection and recurrent glioma. Local signs like
suppuration of the wound could be observed in 71% of patients with intracranial
infection. Postoperative abscesses had been diagnosed in all cases within 3
months, whereas none of the early recurrences of intracerebral malignoma became
symptomatic before 12 weeks after initial operation. Therefore, the course of
time seems to be another important factor in this differential diagnosis.
PMID- 9637199
TI - Genetic and environmental risk factors in Parkinson's disease.
AB - Parkinson's disease (PD) is a multifactorial disorder, caused by a combination of
age, genetics and environmental factors. Nigral cells are susceptible to multiple
causes of derangement of normal cell function, all of which may contribute to the
same Parkinson phenotype. Autosomal dominant alpha-synuclein-gene PD represents
one of the pure genetic forms, whereas cases of sporadic PD probably depend more
on age and environmental factors, MPTP-Parkinsonism being the purest example of
an environmentally caused Parkinson phenotype. This review suggests that
pesticides-herbicides, smoking and head trauma probably represent the most
eligible candidates for environmental factors involved in provoking PD or
influencing its natural course.
PMID- 9637200
TI - Proton magnetic resonance spectroscopy in deep cerebral venous thrombosis.
AB - A 63-year-old man developed a severe left frontal headache followed by an acute
change of mentality 6 days later. Magnetic resonance imaging revealed bilateral
thalamic ischemia. Angiography confirmed the occlusion of deep cerebral veins.
Proton magnetic resonance spectroscopy (1H-MRS) of the thalami showed normal N
acetylaspartate (NAA) peak and the presence of lactate peak, indicating a
relatively preserved neuronal viability. The patient improved during the follow
up period, and returned to work 45 days after the onset of the disease. With 1H
MRS, prognosis following venous infarctions may be feasible.
PMID- 9637201
TI - Transient visual blurring, retro-orbital pain and repetitive involuntary
movements in unilateral carotid artery occlusion.
AB - An 83-year-old man presented with episodes of right sided retro-orbital pain,
visual disturbance, involuntary jerks of his left arm and less frequently his
left leg. The symptoms could be triggered by exercise, heat or cough. EEG
recordings revealed no epileptic discharges. Duplex ultrasonography showed an
occlusion of the right internal carotid artery. Blood flow velocity in the right
middle cerebral artery was reduced and vasomotor reactivity to hypercapnia was
absent. Reduction of his antihypertensive medication rendered the patient
asymptomatic. The combination of transient visual blurring, retro-orbital pain
and contralateral limb shaking can be an unusual manifestation of carotid
occlusive disease. In such a case, the symptoms may be managed successfully by
the elevation of blood pressure.
PMID- 9637202
TI - Intracranial hypotension syndrome: neuroimaging in five spontaneous cases and
etiopathogenetic correlations.
AB - Intracranial hypotension (IH) is essential or, more frequently, secondary. This
syndrome is characterized by severe postural headache and low opening
cerebrospinal fluid (CSF) pressure; although other symptoms may exist. In this
study five patients are investigated. Neuroimaging showed: on computerized
tomography scan (CT), poor visualization of the cerebral sulci with small
ventricles; on magnetic resonance imaging (MRI), subdural fluid collections with
enhancement on the convexity, along the tentorium and in the upper cervix after
administration of contrast medium and downward displacement of the brain.
Radionuclide cisternography was normal in the two patients who underwent this
treatment as well as the meningeal biopsy in another patient. In all patients the
opening CSF pressure was low or unmeasurable. The clinical syndrome spontaneously
recovered contextually to normalization of neuroradiological findings. The
possible pathogenesis (dural border cell layer tear) was discussed and the
importance of diagnostic confirmation with MRI and measurement of CSF pressure
when IH is thought to be present was underlined.
PMID- 9637203
TI - Visual improvement during octreotide therapy in a case of episellar meningioma.
AB - Meningiomas of the tuberculum sellae can induce compression of the optic tract.
We report the case of a 54-year-old female patient affected by a suspected
pituitary macroadenoma with severe visual field defects, who experienced a
significant clinical and visual improvement during short-term octreotide therapy,
contrasting with the lack of neuroradiological evidence for tumor shrinkage. The
patient subsequently underwent transcranial surgery with a final diagnosis of
meningioma. The putative mechanisms of visual improvement during octreotide
therapy are discussed.
PMID- 9637204
TI - The forgotten condyle: Delayed hypoglossal nerve palsy caused by fracture of the
occipital condyle.
AB - Fracture of the occipital condyle is a rare injury that can be easily overlooked.
Palsies of lower cranial nerves can be the only symptom of the fracture. We
report a patient with isolated post-traumatic hypoglossal nerve palsy who
developed hypoglossal nerve palsy within 2 months after a car accident,
indicating that the acute trauma itself did not damage the hypoglossal nerve.
Most likely the palsy is caused by pressure to the nerve prior to the entry or
within the hypoglossal canal. Since, in the present case, the fracture was stable
and the patient showed only moderate neurological deficits, the operation was
deferred.
PMID- 9637205
TI - Posthemiplegic focal limb dystonia: a report of two cases.
AB - Posthemiplegic focal limb or hemidystonias are rare movement disorders usually
due to vascular lesions of the contralateral basal ganglia. The pathogenesis of
posthemiplegic dystonia is unknown and its management is usually difficult. In
this paper, we report two patients who suffered from a single limb dystonia and
hemidystonia, respectively. In the latter patient, hemidystonia developed due to
an ischaemic cerebrovascular accident 2 or 3 months after the recovery of
hemiplegia. Computed tomography and magnetic resonance imaging scans showed
evidence of contralateral putamen and thalamus infarcts.
PMID- 9637206
TI - Reversible blindness in AIDS-related cryptococcal meningitis.
AB - A 30-year-old AIDS-patient with cryptococcal meningitis developed subacute
bilateral visual loss associated with high cerebrospinal fluid (CSF) pressure.
With immediate CSF drainage the blindness was reversible. The importance of
prompt CSF drainage in AIDS-related cryptococcal meningitis with visual failure
is stressed.
PMID- 9637207
TI - Demyelinating polyneuropathy with preferentially-proximal involvement.
AB - A 47-year-old man showed progressive, symmetrical weakness in the limbs for 6
months. There was muscle atrophy, fasciculations, and acute denervation without
motor conduction abnormalities below the elbows or knees, and motor neuron
disease had once been suspected. However, compound muscle action potentials
(CMAPs) after proximal stimulation showed an amplitude reduction between axilla
and Erb's point for the median and ulnar nerves on both sides. His weakness as
well as the amplitude reduction improved after administration of prednisolone.
Demyelinative conduction abnormalities can be limited to the proximal segments
for at least several months in a conduction equivalent to chronic inflammatory
demyelinating polyneuropathy (CIDP).
PMID- 9637208
TI - Malignant cerebellar astrocytoma developing 15 years after radiation therapy for
a medulloblastoma.
AB - A case of malignant cerebellar astrocytoma occurring 15 years after the radiation
therapy for a medulloblastoma is reported. The tumor developed at the same site
of irradiation after a sufficient latent period and was completely different from
medulloblastoma in its histology. This tumor fulfilled the criteria of radiation
induced neoplasm. Only seven similar cases have been reported up to the present.
Whole neuraxis irradiation following a gross total resection is a standard
treatment for medulloblastoma, but the possibility of the development of
radiation-induced tumors must be borne in mind for a long time after the
radiation therapy for medulloblastoma.
PMID- 9637209
TI - Beneficial gamma-knife radiosurgery in a patient with Nelson's syndrome.
AB - A 50-year-old female patient with Cushing's disease had undergone transsphenoidal
removal of the pituitary adenoma and conventional radiotherapy in 1988. Since no
remission was achieved, she underwent bilateral adrenalectomy in May 1989. During
out-patient follow-up, she developed signs and symptoms due to invasive
Adrenocorticotrophic hormone (ACTH)-producing macroadenoma (Nelson's syndrome) in
1994. ACTH levels at that time were 3400 ng/l. Near-total surgical resection of a
2.0 x 2.5 pituitary tumour which slightly extended laterally into the cavernous
sinus was achieved by subfrontal approach in June 1994. However, she rapidly
developed a recurrence of her complaints, with a visual field defect inferior
nasal of the left eye, and a second operation was carried out in November 1994.
Culture of the tumour's cells revealed significant inhibition of ACTH production
by bromocriptine. Adjuvant treatment with this drug therefore was started in
November 1994. Because of the rapid recurrence it was decided to treat her with
gamma-knife radiosurgery. The dose that was given in January 1995 was 12 Gy to
the border and 40 Gy into the centre of the tumour. During a follow-up of more
than 2 years, no recurrence, but even a minor reduction of tumour mass was
observed by magnetic resonance imaging (MRI). Plasma ACTH levels decreased
gradually to levels between 200 and 400 ng/l, and ophthalmologic complaints
disappeared. It is concluded that gamma-knife radiosurgery may be a good
alternative for patients with Nelson's syndrome who have rapidly recurring
disease.
PMID- 9637210
TI - A new form of complicated hereditary spastic paraplegia with cataracts, atretic
ear canals and hypopigmentation.
AB - A 16-year-old Hispanic boy born of consanguineous parents is described as having
a history of cataracts, progressive lower-extremity spasticity and atrophy
starting at 4 years of age, atretic ear canals with hearing dysfunction and
diffuse patchy cutaneous hypopigmented areas. Clinical examination showed the
typical signs of spastic paraplegia with increased tone, hyperreflexia, muscle
atrophy and contractures. Sensation, autonomic and cerebellar functions were not
disturbed. Neuroimaging studies were normal. Laboratory findings did not support
a diagnosis of metabolic disturbance or infectious disease. This is considered a
new form of complicated hereditary spastic paraplegia (HSP), transmitted
presumably in an autosomal recessive pattern.
PMID- 9637211
TI - Vestibular schwannoma with repeated intratumoral hemorrhage.
AB - A symptomatic hemorrhage from a vestibular schwannoma is extremely rare, despite
its relatively high incidence in the cerebellopontine angle. Much more unusual
are repeated intratumoral hemorrhages. The authors report on such a rare case of
repeated intratumoral hemorrhage from a vestibular schwannoma, presenting with
sudden exacerbation of headache, nausea and vomiting. This second hemorrhage was
confirmed by CT scan on the day of the onset of symptomatic exacerbation, which
was 9 days after the initial CT scan, showing an enlarged amount of blood within
the tumor. The MRI scan confirmed this CT finding. After removal, the tumor
proved to be a typical vestibular schwannoma of mixed Antoni types A and B. Thin
dilated vessels with hemorrhage and hemosiderin-laden macrophages were observed.
The patient's postoperative course was uneventful. A total of 28 reported cases
of a single intratumoral hemorrhage in vestibular schwannomas, and one reported
case of repeated hemorrhage are reviewed.
PMID- 9637212
TI - Familial cortical tremor with epilepsy: an under-recognized familial tremor.
AB - The authors report three Japanese families presenting with cortical tremor and
epilepsy. The patients showed either tremulous finger movements or seizures as
the initial symptoms between 19 and 30 years of the age without progression.
Postural tremor resembled essential tremor and responded to the anticonvulsants
such as clonazepam, primidone and sodium valproate. Seizures were infrequent.
These patients seem to have the same disorder as what the authors have described
as 'familial cortical tremor with epilepsy'. Familial cortical tremor must be
more common than previously thought and should be taken into consideration in the
patients with 'familial essential tremor' who do not respond well to beta
blockers.
PMID- 9637213
TI - Seroprevalence of Babesia ovis in Spanish ibex (Capra pyrenaica) in Catalonia,
northeastern Spain.
AB - A serologic survey was carried out in order to detect antibodies against Babesia
ovis in a large population of Spanish ibex (Capra pyrenaica) from a hunting
reserve in Catalonia, northeastern Spain. For this purpose, an indirect
fluorescent antibody test (IFAT) was developed using a B. ovis isolate of ovine
origin as antigen. Of the total 475 sera tested, 155 (32.6%) showed titres
between 1:160 and 1:1280 and were considered positive. These results reveal that
exposure of Spanish ibex to B. ovis is common in the studied area. No significant
differences could be detected when comparing season or year of capture and age or
sex of the animals in positive and negative samples. A high proportion of low
titres was found in comparison to those reported by other researchers in sheep in
Spain; this could be a consequence of the existence of some minor antigenic
differences between B. ovis of domestic sheep and that found in Spanish ibex.
PMID- 9637214
TI - The efficacy of Michel's dose and move system on gastrointestinal nematode
infections in diary calves.
AB - The efficacy of a move to aftermath in July combined with moxidectin or
fenbendazole treatment for the control of parasitic gastroenteritis (PGE) in
calves was evaluated in three field experiments in the Netherlands. In all five
treated groups high gastrointestinal nematode infections and PGE were prevented
by a dose and move in July. Cooperia infections increased to moderate levels in
two groups treated with moxidectin and one group treated with fenbendazole. In
both other groups and also for Ostertagia in these three groups, low to extremely
low infections were acquired. In the first experiment high primary infections,
resulting in high faecal egg counts and a moderate increase of blood pepsinogen
values occurred before the dose and move. Nevertheless, these primary infections
were not high enough to result in PGE. In both other experiments primary
infection levels were low and faecal egg counts increased to 100-650 eggs/g
faeces at the end of the grazing season. The blood pepsinogen values of non
treated control groups demonstrated that it took more than a month after their
move to aftermath before substantial reinfection occurred on the new pasture. In
the first and the last experiment only, high Ostertagia and Cooperia infections
developed in the control group at the end of the grazing season, though it did
not result in clinical PGE. The experiments demonstrate all theoretical risks of
the dose and move system: (1) PGE early in the grazing season as a result of high
overwintered pasture infectivity. (2) PGE just before the move as a result of an
early midsummer increase in pasture infectivity. (3) PGE around housing as a
result of insufficient suppression of pasture infectivity late in the grazing
season. (4) Underexposure to nematode infections due to a high suppression of
nematode infections. Nevertheless, it can be concluded that under normal
conditions the dose and move system remains to be a valuable and easily
applicable system for the control of PGE.
PMID- 9637215
TI - Gastrointestinal nematode infections of first-grazing season calves in Western
Europe: general patterns and the effect of chemoprophylaxis.
AB - Research on the prevention of gastrointestinal nematode infections of cattle has
mainly concentrated on comparing a specific chemoprophylactic treatment system to
an untreated control group on a particular farm. Here, the results from analysis
of 85 studies involving over 2000 first grazing season (FGS) calves put onto
pasture for at least 4 months from late spring/early summer over a 26-year period
in 13 countries in Western Europe are presented. Both control and
chemoprophylactic treated FGS calf groups were considered. All chemoprophylactic
systems (slow- and pulse-release boli, strategic treatments) were given early in
the grazing season. Two general infection levels emerged--'sub-clinical' (32
studies) and 'clinical' (53 studies). The 'sub-clinical' infections were
characterised by no clinical symptoms of parasitic gastroenteritis (PGE) being
observed in the control groups. Mean faecal egg counts in the 'clinical' control
groups were significantly higher than those for 'sub-clinical' control groups for
almost the entire season with overall peaks of 275 and 100 EPG respectively.
Maximum pasture larval counts were also significantly higher in the 'clinical'
control groups with 44% of 'clinical' pastures > 10,000 L3 kg(-1) dry herbage by
the end of the FGS, compared to only 15% of 'sub-clinical' pastures. There was a
significant positive relationship between log transformed worm burdens from
tracers put onto pastures for 2 weeks and the corresponding pasture larval count.
No evidence of density dependence in tracer worm burden was observed. Weight
gains in the 'clinical' control groups (375 g/day) were significantly lower than
those of the 'sub-clinical' control groups (530 g/day). No symptoms of PGE were
observed in any of the chemoprophylactic treated groups, but in those studies
with an outbreak of PGE in the control group, the treated groups had
significantly higher faecal egg and pasture larval counts than treated groups in
'sub-clinical' studies. The overall weight gain in chemoprophylactic treated
calves in 'clinical' studies (600 g/day) was significantly lower than the
chemoprophylactic treated calves in 'sub-clinical' studies (690 g/day), and was
not significantly different from the weight gain of control calves in 'sub
clinical' studies. These results indicate that on heavily infected pastures,
chemoprophylaxis will prevent PGE, but calves will still suffer production
losses.
PMID- 9637216
TI - Gastrointestinal nematode infections of first-grazing season calves in Western
Europe: associations between parasitological, physiological and physical factors.
AB - Analysis of 85 studies on gastrointestinal nematode infections in first-grazing
season (FGS) calves is presented. The studies cover a 26-year period and were
carried out in 13 countries in Western Europe. Both control and chemoprophylactic
treated (early in the season) FGS calf groups were included. In 53 of the 85
studies, clinical outbreaks of parasitic gastroenteritis (PGE) were observed
during the FGS in the control groups. The mean initial age (and weight) of the
control calf group was significantly associated with PGE outbreaks: 82% of
control calf groups < or = 6 months of age had outbreaks of PGE, compared to only
33% of control calf groups > 6 months of age. In 92% of trials where the
geometric mean faecal egg count (MFEC) was > or = 200 EPG on Day 56, PGE
outbreaks were observed, but where it was < 200 EPG, only 29% had PGE. The use of
these two factors in assessing the likelihood of PGE outbreaks in untreated calf
groups in the future FGS is therefore, proposed. No chemoprophylactic-treated
groups had PGE, but there was a highly significant negative relationship between
maximum faecal egg counts in the chemoprophylactic-treated calves and the
proportion of the trial covered by the different chemoprophylactic systems.
Higher stocking densities were significantly associated with higher pasture
contamination in both control and chemoprophylactic-treated calves. A highly
significant positive relationship between the weight gained in the
chemoprophylactic-treated groups and the estimated duration of the various
chemoprophylactic systems was found, but there were large variations in weight
gains (60-160 kg) between groups even with the same chemoprophylactic. Despite
this and other highly significant associations, it was not possible to indicate
what weight gains were obtained by the end of the FGS, from factors measured
early in the FGS.
PMID- 9637217
TI - The effect of different infection levels on acquired resistance to
gastrointestinal nematodes in artificially infected cattle.
AB - The objective of this study was to evaluate the effect of different infection
levels of Ostertagia ostertagi and Cooperia oncophora in a simulated 'first
grazing season' on the resistance of calves to an artificial challenge infection.
The infection levels were determined by the infection schedules and the
chemoprophylaxis used. Thirty six 7-11-month old Holstein-Friesian bull calves
were randomly divided into four groups. The animals of group B received an
ivermectin sustained release bolus (ISRB) on day 0. The calves of group D were
treated on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg(
1) BW). Group C was the untreated control group. The calves of group N were used
as helminth-naive controls, while the animals of groups B, C and D were trickle
infected for 24 weeks. The infection schedules were designed to simulate the
expected infection pattern for each treatment group under set-stocked conditions
in temperate climate areas. After the last infection, all animals were treated
with oxfendazole. One week later, all animals received a challenge infection of
50,000 O. ostertagi L3 and 100,000 C. oncophora L3, spread over 10 consecutive
days. During the primary infection period the faecal egg output and the serum
pepsinogen and antibody levels reflected the different levels of host-parasite
contact between the groups (group C > group D > group B > group N). After the
challenge infection, faecal egg counts, total Ostertagia burden, size of the
adult worms and abomasal globule leucocyte counts all indicated a positive
relationship between the level of Ostertagia infection during the primary
infection period and the level of acquired resistance. A reduction of host
parasite contact during the primary infection period, as a consequence of the
infection schedule and the chemoprophylaxis used, resulted in a diminished level
of resistance to the artificial challenge infection with O. ostertagi. Faecal
cultures and small intestine worm counts indicated that all previously infected
groups had acquired a high degree of resistance to the Cooperia challenge
infection.
PMID- 9637218
TI - Field evaluation of a topical doramectin formulation for the chemoprophylaxis of
parasitic bronchitis in calves.
AB - A study was conducted to evaluate the efficacy of two topical treatments with
doramectin on the season-long control of lungworm and gastrointestinal infections
in first grazing season (FGS) calves. At the start of the study, 20 FGS calves
were randomly allocated into two treatment groups of 10 animals each. Calves in
the D-group were treated with doramectin pour-on on days 0 and 56, at a dosage of
500 microg kg(-1) BW: calves in the C-group were designated as controls. A
permanent pasture was divided in two blocks and these were randomly allocated to
the treatment groups. Throughout the study, tracers (n = 32) were grazed on each
paddock at 3-week intervals. Clinical signs of parasitic bronchitis (PB) were
observed in the C-group in July and this necessitated two salvage treatments with
levamisole. From day 28, post-turnout lungworm larvae were recovered from faeces
of the C-calves until housing. No signs of PB were observed in the D-group during
the entire grazing season. Shedding of lungworm larvae in the principals of the D
group did not occur until 112 days post-turnout. From the data obtained from the
tracer calves. it appeared that larvae had overwintered on both pastures. On the
C-pasture, the number of lungworms recovered from the tracer calves gradually
increased to a peak in September, whereas on the D-pasture, the increase was
observed only at the end of the pasture season. Both strongyle faecal egg counts
and pepsinogen levels were relatively low in both groups throughout the present
study. At the end of the grazing period (day 161). the principals were housed and
treated with oxfendazole. During the housing period, all principal animals (D-
and C-groups) and a third group of four helminth free animals (N-group) received
a challenge infection with Dictyocaulus viviparus. It appeared that the different
exposure to the parasite during the grazing season resulted in different
establishment rates, i.e.. group C < group D < group N. The present results show
that overwintering of lungworm larvae occurs in Belgium and that in such
conditions, doramectin pour-on given at turnout and at 8 weeks controls PB in
calves during the first grazing season.
PMID- 9637219
TI - Embryonation and infectivity of Ascaris suum eggs isolated from worms expelled by
pigs treated with albendazole , pyrantel pamoate, ivermectin or piperazine
dihydrochloride.
AB - The effect of anthelmintic treatment of pigs on the embryonation and infectivity
of Ascaris suum eggs isolated from expelled worms was investigated. Four groups
of two naturally infected pigs were dosed with albendazole, pyrantel pamoate,
ivermectin or piperazine dihydrochloride, respectively. Following worm expulsion,
the eggs were removed from the uteri of female worms and embryonated in sulphuric
acid. The infectivity of the embryonated eggs was tested through mouse
inoculation. Egg development appeared normal in cultures from worms of the
piperazine. pyrantel and ivermectin treated groups. In the albendazole cultures,
egg development was largely arrested at the one-cell stage (81%). Where
development occurred, irregular cell division was observed and only 7% of the
eggs in the culture developed into fullgrown larvae. Following mouse inoculation
with 2500 embryonated eggs, significantly lower lung larval counts on day 8 post
inoculation (p.i.) were observed for mice in the piperazine and pyrantel treated
groups (P < 0.01) compared to untreated controls. The larvae that developed in
the eggs from ivermectin and albendazole treated groups appeared fully infective
for mice. It was concluded that ovicidal activity of albendazole in vivo inhibits
subsequent A. suum egg development in vitro; albendazole is, therefore, not
suitable to obtain worms for egg embryonation to produce experimental inoculums.
The anthelmintic treatment of pigs with ivermectin had only a limited effect on
both embryonation and infectivity of A. suum eggs isolated from expelled worms.
PMID- 9637220
TI - Multiple anthelmintic resistance on a goat farm in Kenya.
AB - The anthelmintic efficacy of benzimidazoles, levamisole, rafoxanide and
ivermectin was evaluated on an institutional farm in Kenya using faecal egg count
reduction test, larval cultures and a controlled slaughter trial. The results of
this study indicated simultaneous resistance of Haemonchus contortus against
benzimidazoles, levamisole and rafoxanide and Trichostrongylus columbriformis and
Oesophagostomum sp. against levamisole on the same farm. Injectable and orally
administered ivermectin was effective against the benzimidazole and levamisole
resistant H. contortus.
PMID- 9637221
TI - Interpreting comparative experiments on parasite burdens in animals using
randomization and canonical variates.
AB - Comparative experiments on parasite burdens present difficulties for modelling
and interpretation: data tend to have highly skewed distributions, some standard
methods of testing for effects have low power, and there is a need to make
allowance for dependencies among the various measurements. Randomization testing
and canonical variates analysis are advocated as a means of minimising these
problems.
PMID- 9637222
TI - Methimazole-mediated enhancement of albendazole oral bioavailability and
anthelmintic effects against parenteral stages of Trichinella spiralis in mice:
the influence of the dose-regime.
AB - The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the
systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole
sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic
effects was investigated in a mouse model for helminthic infections. Plasma
concentrations of the ABZS-MT were measured by high performance liquid
chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole
(ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic
effects were assessed in age-matched mice similarly treated following infection
with Trichinella spiralis. MTZ significantly (p < 0.01) increased the ABZS-MT
plasma concentrations although the pharmacokinetic profile varied greatly
according to the dose of ABZ administered. When ABZ was given at a single dose of
50 mg/kg followed by MTZ at 3 mg/kg, a cumulative effect was observed in the ABZS
MT plasma levels with pharmacokinetic parameters (Tmax = 24 h, Cmax= 30.88
microg/ml and AUC = 1120.80 microg h/ml) significantly ( p < 0.01) higher than
those following administration of ABZ alone (Tmax = 3 h, Cmax = 11.00 microg/ml
and AUC = 268.03 microg h/ml). This cumulative effect was absent following
administration of ABZ at 100 mg/kg where, after reaching a maximum (Cmax = 27.23
microg/ml) at 3 h post-administration (Tmax), the ABZS-MTplasma levels felt down
quickly to values under those obtained after administration of ABZ at the same
dose, but alone (AUC = 362.15 microg h/ml vs. 340.15 microg h/ml, respectively).
When ABZ was given at 50 mg/kg together with MTZ three times every 24 h, a rapid
decrease was observed in the ABZS-MT plasma levels following administration of
both the second and third doses, respectively. The pharmacokinetic profile of
ABZS-MT following administration of each of the three doses of ABZ at 100 mg/kg
plus MTZ was the same as that obtained after the single treatment. The rapid
decrease of the ABZS-MT plasma levels observed after the sustained treatment or
after the single treatment at 100 mg/kg could be due to a microsomal oxidase
inductive effect (probably the cytochrome P-450) caused by ABZSO. The co
administration of MTZ significantly (p < 0.01) increased the anthelmintic effects
of ABZ against both migrating and encysted larvae of T. spiralis. Repeated
treatment did not improve the anthelmintic effects of the single treatment as the
efficacies against both stages of the parasite were always lower or identical to
those of the single treatment at the corresponding doses.
PMID- 9637223
TI - The prevalence of Dirofilaria immitis in Gran Canaria, Canary Islands, Spain
(1994-1996).
AB - Blood samples from 2034 dogs were tested to detect Dirofilaria immitis antigen
during three consecutive years (from 1994 to 1996) in Gran Canaria Island, Canary
Islands, Spain. The prevalence of heartworm infection was 67.02% in 1994, 58.92%
in 1995 and 52.18% in 1996, with a mean prevalence of 58.89%. Heartworm infection
was more common in males (56.19%) than in females (43.81 %), in dogs aged between
3 and 6 years old. The distribution of the disease in the different climatic
zones was studied. Chronological changes in the dog's prevalence for heartworm
infection in the three consecutive years and the role of the epidemiological
factors in the changes of the positive rates were evaluated.
PMID- 9637224
TI - Studies on the survival of Ascaris suum eggs under laboratory and simulated field
conditions.
AB - A series of four experiments was carried out to study the survival of Ascaris
suum eggs: in a pig slurry unit on a farm, in the laboratory under anaerobic
conditions and different relative humidities (rH), and under simulated field
conditions. Survival of eggs in the pig slurry unit was 20% after four weeks and
0% after 16 weeks. Anaerobic conditions had only a minor influence on survival:
after 12 weeks, more than 80% of the eggs could still develop. At high relative
humidities (100% and 75%), survival was respectively 96% and 62% after 12 weeks.
At 47.5% rH, survival dropped to 0% after 10 weeks and at 7.5% rH in 8 weeks. A.
suum eggs kept in pig slurry under dry and sunny outdoor conditions survived for
2-4 weeks, whereas under wet and shady conditions, 90% of the eggs were still
viable after 8 weeks.
PMID- 9637225
TI - Gastrointestinal helminth parasites in stray cats from the mid-Ebro Valley,
Spain.
AB - Gastrointestinal helminths were collected from 58 necropsied stray cats (Felis
catus) in the mid-Ebro Valley, North-East Spain, from December 1989 to March
1992. The prevalence was 89.7%, with those of individual parasites being Toxocara
cati 55.2%C, Ancylostoma tubaeforme 29.3% Joyeuxiella pasqualei 55.2%,
Diplopylidium acanthotetra 20.7%, Dipylidium caninum 20.7%, Mesocestoides spp.
13.8%, Taenia taeniformis 8.6% and Diplopylidium nolleri 8.6%. In relation to
sex, the differences were not significant. However, the season of the year
significantly affected the prevalence of A. tubaeforme and D. acanthotetra.
PMID- 9637226
TI - Development, reproductive capacity and survival of Amblyomma variegatum and
Boophilus decoloratus in relation to host resistance and climatic factors under
field conditions.
AB - To determine the developmental periods, fecundity and survival of Amblyomma
variegatum and Boophilus decoloratus and the effect of host resistance, a study
was carried out in the field at Abernossa ranch in Ethiopia using three breeds of
cattle: Arssi, Boran and Boran x Friesian crossbreed. The investigation took
place between October 1991 and September 1992. The developmental periods of both
tick species were recorded. The hatching periods of larvae, engorgement, larvo
nymphal and nympho-adult moulting periods during various climatic seasons in
shaded and dry areas were also recorded. While the engorgement periods recorded
on the animal were relatively constant for each tick species throughout the
period of investigation, the pre-hatching and moulting periods were influenced by
seasons. Generally, the duration of the life cycle was longest during the peak of
rains and shortest during the dry season. In A. variegatum, the duration of the
life cycle, irrespective of seasons, was shorter in the open than in the shaded
site but this difference was not observed in B. decoloratus. Adults survived
longer than nymphs, and nymphs longer than larvae in both tick species and A.
variegatum survived much longer than B. decoloratus. All these variations were
statistically significant (P < 0.001). A. variegatum and B. decoloratus fed on
Boran X Friesian crossbreed cattle survived longer than ticks fed on the
indigenous Boran and Arssi breeds, although the survival of both tick species fed
on the latter two breeds was not significantly different from each other. The
least tick resistant cattle (Boran X Friesian) produced the largest ticks with
highest survival periods, whereas the most resistant indigenous cattle (Arssi and
Boran) cattle produced the smallest ticks with the lowest survival periods. In
all cases, more eggs were laid by A. variegatum than by B. decoloratus. However,
in both tick species, the number of eggs laid and their hatchability were higher
in those ticks fed on crossbreed than on indigenous cattle. The engorgement
weights were positively correlated with the number of eggs laid and their
hatchability.
PMID- 9637227
TI - Efficacy of orally administered invermectin against larval stages of Oestrus ovis
in sheep.
AB - The efficacy of ivermectin administered orally at a dosage rate of 0.2 mg/kg
liveweight against naturally acquired larval infestations of Oestrus ovis in
sheep was 100% in a field trial. Ten sheep were free from infestation by first,
second and third instar larvae of O. ovis 12 days post treatment, whereas 10
control sheep harboured 37.7 larvae on average, most of them first stage.
PMID- 9637228
TI - Delayed type hypersensitivity theilerin test in cattle vaccinated against
Theileria annulata infection.
AB - Theilerin was prepared and its total nitrogen was determined at level of 1 mg/ml.
Seventy-two Holstein Friesian cattle recovered from acute theileriosis or
vaccinated received 0.1 ml of theilerin intradermally at normal concentration of
total nitrogen or other dilutions (1 / 10 and 1 / 100). Some 60(% of calves and
66.67% of milking cows receiving normal theilerin showed more than 1 mm increase
in skin thickness at the site of inoculation (mean value of 1.86 mm for calves
and 3.46 mm for milking cows). The pathological examination of the inoculation
site showed infiltration of lymphocytes. No changes of general condition were
observed in animals under study. The result indicated that the test is positive
and could be used for checking Immunity in vaccinated animals.
PMID- 9637229
TI - Prevalence of Tritrichomonas foetus infection in beef bulls in northwestern
Spain.
AB - The purpose of this study was to investigate the prevalence of Tritrichomonas
foetus infection in beef bulls in north-western Spain. The study area comprised
of 350 herds (5909 cows and 102 bulls) managed under extensive or semi-extensive
systems where natural mating alone or alternated with artificial insemination are
used. The targets of this survey were bulls of 1 year of age or older. Preputial
smegma samples were taken from 70 bulls (68.6% of bull population) servicing a
total of 184 herds (52.6%) and 4136 cows (69.9%). Data collected at sampling
included farm location, herd size, age, breed, private or communal bull and
previous infertility problems in the herd. The percentage of infected bulls was
2.9% (2 of 70). Age of infected bulls was 5 and 7 years and both were of the
local breed, Asturiana de los Valles. These results confirm the presence of T.
foetus infection in Spain and the necessity to include this disease in the
differential diagnosis of reproductive failure in rangeland grazing cattle.
PMID- 9637230
TI - Prevalence of Neospora caninum and Toxoplasma gondii antibodies in sera from
camels from Egypt.
AB - Sera from camels from Egypt were examined by the direct agglutination tests
incorporating mercaptoethanol for antibodies to Neospora caninum and Toxoplasma
gondii. Antibodies to N. caninum were found in 6 of 161 camels in titers of 1:40
(2 camels) and 1:80, 1:160, 1:640, and 1:1280 in 1 camel each, using N. caninum
formalin preserved whole tachyzoites as antigen. Antibodies to T. gondii were
found in 17.4% of 166 camels in titers of 1:25 (3 camels), 1:50 (18 camels). and
> 1:500 (8 camels) using T. gondii tachyzoites. All 6 camels with N. caninum
antibodies had no T. gondii antibodies in 1:4 dilution of serum, indicating
specificity of the reaction. This is the first report of N. caninum prevalence in
Egypt.
PMID- 9637231
TI - Disseminated feline leishmaniosis due to Leishmania infantum in Southern France.
AB - A fortuitously discovered case of feline leishmaniosis is reported. The parasites
were found in the skin and the bone marrow of a domestic female cat that
spontaneously died after a few weeks of evolution. Serological tests for FeLV,
FIV and PIF virus detection gave negative results. By using Western blot
serology, a characteristic pattern of leishmaniosis was obtained and by
performing an isoenzyme electrophoresis, a Leishmania infantum MON-1 strain was
identified. The same zymodeme is implicated in most of the canine and human
leishmaniosis in Southern Europe. A study on the prevalence of asymptomatic
feline leismaniosis is foreseen.
PMID- 9637232
TI - Preliminary studies on humoral immune response of sheep to wohlfahrtiosis.
AB - The humoral immune response of sheep to wohlfahrtiosis was studied. An enzyme
linked immunosorbent assay was developed to compare four different types of
antigens obtained from the third-stage larvae of Wohlfahrtia magnifica. The
antigen prepared from salivary glands detected a humoral response in all 35
infested sheep and was more specific in the ELISA than cuticular, intestinal or
whole larval antigens. The level of the humoral response in sheep to
wohlfahrtiosis differed according to the location of the wounds.
PMID- 9637233
TI - The genetic effects of environmental lead.
AB - This article reviews the effects of lead on genetic systems in the context of
lead's various other toxic effects and its abundance and distribution in the
environment. Lead is perhaps the longest used and best recognized toxic
environmental chemical, yet it continued be used recklessly until only very
recently. Lead is thus a lesson in the limitations and strengths of science,
human conscience and common sense. Lead has been tested and found to be capable
of eliciting a positive response in an extraordinarily wide range of biological
and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA
synthesis, mutation, chromosome aberrations, cancer and birth defects. It reacts
or complexes with many biomolecules and adversely affects the reproductive,
nervous, gastrointestinal, immune, renal, cardiovascular, skeletal, muscular and
hematopoietic systems as well as developmental processes. It is likely that lead
is a selective agent that continues to act on and influence the genetic structure
and future evolution of exposed plant and animal populations.
PMID- 9637234
TI - Genetic, carcinogenic and teratogenic effects of radiofrequency fields.
AB - This paper reviews the literature data on the genetic toxicology of
radiofrequency (RF) radiation. Whereas in the past most studies were devoted to
microwave ovens and radar equipment, it is now mobile telecommunication that
attracts most attention. Therefore we focus on mobile telephone frequencies where
possible. According to a great majority of the papers, radiofrequency fields, and
mobile telephone frequencies in particular, are not genotoxic: they do not induce
genetic effects in vitro and in vivo, at least under non-thermal exposure
conditions, and do not seem to be teratogenic or to induce cancer. Yet, some
investigations gave rather alarming results that should be confirmed and
completed by further experiments. Among them the investigation of synergistic
effects and of possible mechanisms of action should be emphasised.
PMID- 9637235
TI - Teratogenic and reproductive effects of low-frequency magnetic fields.
PMID- 9637236
TI - Animal and cellular studies on carcinogenic effects of low frequency (50/60-Hz)
magnetic fields.
PMID- 9637237
TI - Repair of DNA damage in mammalian cells after treatment with UV and dimethyl
sulphate: discrimination between nucleotide and base excision repair by their
temperature dependence.
AB - Alkylating agents have been reported to give rise to both short and long patches
of repair. The reason for the different patch sizes is not known. One possibility
is that alkylating agents can trigger both base and nucleotide excision repair.
Another possibility is that base excision repair itself can result in different
patch sizes. Recognition and incision at lesions is the rate limiting step in
excision repair. In order to discriminate between base and nucleotide excision
repair it would be desirable to be able to distinguish between different incision
activities. In order to accurately measure incision rates, the rejoining of the
strand-breaks formed must be inhibited. We have used two inhibitors, aphidicolin
and 3-aminobenzamide. Aphidicolin, an inhibitor of DNA polymerases
alpha/delta/epsilon. caused accumulation of single-strand breaks both after UV
and dimethylsulphate. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose)
polymerase caused accumulation of single-strand breaks only after alkylating
agents and is thus specific for base excision repair. Enzymatic activities can be
characterised by their activation energy. In order to discriminate between base
and nucleotide excision repair the temperature dependence of incision activities
was determined. When the temperature is decreased, the incision rate is reduced
to a larger extent for UV than for DMS-induced repair. Incisions in UV-irradiated
cells are practically cut off at temperatures of 15 degrees C and below, whereas
DMS-exposed cells still are actively repairing at this temperature. In DMS
treated cells the temperature dependence was the same whether aphidicolin or 3
aminobenzamide was used, speaking against an involvement of nucleotide excision
repair. In addition, cell lines deficient in nucleotide excision repair responded
in the same way to aphidicolin after DMS treatment as normal cells and were able
to make incisions at 15 degrees C. This indicates that nucleotide excision repair
is not to any significant amount involved in repair of DNA damage induced by a
methylating agent.
PMID- 9637238
TI - Kinetics of DNA strand breaks and protection by antioxidants in UVA- or UVB
irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay.
AB - The aim of this study was to characterize the genotoxic action of UVA and UVB in
human keratinocytes by application of the single cell gel electrophoresis assay
(SCGE assay). Dose dependence of DNA damage, the time course of its repair, and
the influence of cellular antioxidant status were assessed. Irradiation with UVA
or UVB both resulted in a dose-dependent increase in the level of DNA damage. A
time course study to evaluate the repair kinetics in keratinocytes irradiated
with 5 J/cm2 UVA revealed an immediate occurrence of DNA effects which
subsequently disappeared within about 1 h, indicating removal of DNA lesions.
This rapid repair of DNA damage is consistent with the observation that 5 J/cm2
UVA did not impair cellular viability. In contrast, exposure to 15 mJ/cm2 UVB
resulted in a prolonged repair of DNA damage which lasted about 25 h. Thus, the
repair kinetics of UVA- and UVB-induced DNA damage clearly differed from each
other, implicating the induction of different types of DNA lesions by UVA and
UVB. Neither a pretreatment with Mg-ascorbyl phosphate or D,L-alpha-tocopherol,
nor depletion of endogenous glutathione altered cellular sensitivity to UVB. In
contrast, the DNA damaging effects of UVA could be counteracted by a pretreatment
with these antioxidants. These observations confirm that the UVA-induced effects
on DNA are related to radical mediated strand breaks and DNA lesions forming
alkali-labile sites. The UVB-induced effects mainly occur as a consequence of
excision repair-related strand breaks. The observed repair kinetics of DNA
lesions and the influence of cellular antioxidant status may help to elucidate
protective mechanisms against the carcinogenic effects of UV radiation present in
sunlight.
PMID- 9637239
TI - Repair in Escherichia coli alkB mutants of abasic sites and 3-methyladenine
residues in DNA.
AB - Escherichia coli alkB mutants are sensitive to methyl methanesulfonate and
dimethylsulphate, and are defective in the processing of methylated DNA. The
function of the AlkB protein has not been determined. Here, we show that alkB
mutants are not defective in repairing several different types of potentially
toxic DNA lesions that are known to be generated by MMS, including apyrimidinic
and apurinic sites, and secondary lesions that could arise at these sites (DNA
protein cross-links and DNA interstrand cross-links). Also, alkB mutants were not
sensitive to MeOSO2-(CH2)2-Lex, a compound that alkylates the minor groove of DNA
generating primarily 3-methyladenine.
PMID- 9637240
TI - A novel plasmid shuttle vector for the detection and analysis of microsatellite
instability in cell lines.
AB - Microsatellite instability is an important feature of tumors from hereditary
nonpolyposis colorectal carcinoma (HNPCC) patients as well as a variety of
sporadic tumors. Here, we present a novel plasmid shuttle vector for the
detection of this replication error (RER+) phenotype in human cell lines. The
episomely replicated plasmid pZCA29 harbours the bacterial beta-galactosidase
gene interrupted by two palindromically arranged poly-(CA)-repeat tracts. The
resulting + 1-frameshift leads to white colonies of Escherichia coli DH10B on X
Gal/IPTG1 agar plates. Mutations in the repeats characteristic of the RER+
phenotype may result in the loss or gain of CA-repeats leading to blue bacterial
colonies. We transiently transfected the colorectal cancer cell lines SW480 and
HCT116 with the plasmid pZCA29, isolated replicated plasmid DNA after several
days and used it to transform E. coli DH10B. We found 1.0 to 1.7% blue colonies
after passage of the plasmid through the RER+-cell line SW480 in contrast to 3.5
to 8.1% blue colonies after transfection of the RER+-cell line HCT116, the
mutation frequencies increasing with incubation time. Sequence analysis of
mutated plasmids revealed mostly 2-bp deletions which occurred especially in one
of the repeat tracts. We conclude that pZCA29 appears to be a suitable shuttle
vector for the detection and analysis of a RER+-phenotype in cell lines.
PMID- 9637241
TI - Genotoxicity and mutagenicity of the alpha, beta-unsaturated carbonyl compound
crotonaldehyde (butenal) on a plasmid shuttle vector.
AB - Crotonaldehyde is an alpha,beta-unsaturated carbonyl compound and an important
environmental and industrial toxic substance. Its mutagenic and carcinogenic
properties are related to its reactivity to DNA, where it forms different guanine
adducts. In order to study the mutagenic consequences of this agent in intact
human cells, we treated the shuttle vector plasmid pZ189 with different doses of
crotonaldehyde at 37 degrees C for 2 h and then transfected the such damaged
plasmid into the normal human lymphoblast cell line GM0621. Within these host
cells the guanine adducts are repaired and the plasmids replicated by cellular
enzymes. After 2.5 days replicated plasmids were purified from the cells and
plasmid survival was quantitated by transformation ability. With increasing doses
of crotonaldehyde, we found a significant decline of plasmid survival, reflecting
a pronounced genotoxicity of crotonaldehyde-induced DNA damage in intact human
cells. Using the plasmid encoded mutagenesis marker gene supF, we were able to
screen for mutants and determine mutation frequency in recovered plasmids. A
significant increase in mutation frequency with increasing doses of
crotonaldehyde reflects mutagenicity of crotonaldehyde-induced DNA damage. Base
sequence analysis of recovered mutants revealed 39% point mutations, 46%
deletions, and 15% insertions and inversions. Most of the point mutations (82%)
were located at G:C base pairs, which is well explained by the DNA damage profile
of crotonaldehyde. Among deletions we found a frequent reoccurrence of two hot
spot deletions, representing 62% of all deletions. The sites of breakpoints of
these deletions hot spots and of other deletions within the plasmid were also
found to be sites of DNA breaks, directly induced by crotonaldehyde, as seen in
an endlabeled plasmid fragment, treated with crotonaldehyde. Further analysis of
the flanking sequences around the deletion breakpoints revealed a high frequency
of four different kinds of short sequence homologies of up to eight base pairs.
PMID- 9637242
TI - Genetic interactions between mutants of the 'error-prone' repair group of
Saccharomyces cerevisiae and their effect on recombination and mutagenesis.
AB - We have created an isogenic series of yeast strains that carry genetic systems to
monitor different types of recombination and mutation [B. Liefshitz, A. Parket,
R. Maya, M. Kupiec, The role of DNA repair genes in recombination between
repeated sequences in yeast, Genetics 140 (1995) 1199-1211.]. In the present
study we characterize the effect of mutations in genes of the 'error-prone' or
postreplicative repair group on recombination and mutation. We show that rad5 and
rad18 strains have elevated levels of spontaneous recombination, both of ectopic
gene conversion and of recombination between direct repeats. The increase in
recombination levels is similar in both mutants and in the rad5 rad18 double
mutant, suggesting that the RAD5 and RAD18 gene products act together with
respect to spontaneous recombination. In contrast, RAD5 and RAD18 play
alternative roles in mutagenic repair: mutations in each of these genes elevate
spontaneous forward mutation at the CAN1 locus, but when both genes are deleted,
a low level of spontaneous mutagenesis is seen. The RAD5/RAD18 pathway of
mutagenic repair is dependent on the REV3-encoded translesion polymerase. We
analyze the interactions between the RAD5 and RAD18 gene products and other
repair genes. The high recombination levels seen in rad5 and rad18 mutants is
dependent on the RAD1, RAD51, RAD52, and RAD57 genes. The Srs2 helicase plays an
important role in creating the recombinogenic substrate(s) processed by the RAD5
and RAD18 gene products.
PMID- 9637243
TI - Quantitative polymerase chain reaction assay for DNA repair within defined
genomic regions.
AB - We have developed a quantitative assay to determine repair of structurally
different DNA lesions at defined genomic sites. This assay depends on the fact
that many different types of damage are repaired by the same nucleotide excision
repair (NER) pathway which includes synthesis of short DNA fragments at the sites
of damage. After exposure to damaging agents, cells are treated with 5
bromodeoxyuridine (BrdUrd) to label the regions undergoing repair with the
presumption that regions that have been more efficiently repaired would
incorporate more BrdUrd than regions that were less effectively repaired. Thus,
the abundance of the different sequences in the BrdUrd-containing DNA would be a
direct and quantitative measure for the repair rates of the corresponding
regions. The BrdUrd-containing, repaired DNA was isolated by CsCl gradient
centrifugation and immunoprecipitation with anti-BrdUrd antibody and was used as
template in quantitative PCR in which the amount of the product was directly
proportional to the amount of template. This approach was used to address the
question whether DNA repair after UV-irradiation occurs in an uniform, random
manner or with preferences for certain regions. We found out that there was a
higher repair efficiency at the 5'-end of the mouse gamma-globin domain in
Ehrlich ascites tumor cells.
PMID- 9637244
TI - Altered UV resistance and UV mutational spectrum in repair-proficient murine
fibroblasts expressing endonuclease V.
AB - In previously reported studies, we transfected repair-proficient murine
fibroblasts with the denV gene of bacteriophage T4 and showed that expression of
encoded endonuclease V markedly enhanced cyclobutane pyrimidine dimer (CPD)
repair and reduced the frequency of ultraviolet radiation (UV)-induced mutations.
In the present studies, we compared the spectra of UV-induced mutations at the
hprt locus in denV-transfected and control cells. A significant difference in
mutation types was observed. While multiple base deletions and single base
insertions were found in denV-transfected but not control cells, multiple tandem
and non-tandem point mutations identified in control cells were absent in denV
transfected cells. When we compared colony survival following UV exposure in the
two cell lines, it appeared that endonuclease V expression did not enhance UV
resistance, instead denV-transfected cells had increased susceptibility to low
fluences of UV. The effects of endonuclease V expression on UV resistance and on
UV mutational spectrum are likely to be due both to the removal of CPDs and to
the novel enzymatic activity of endonuclease V.
PMID- 9637245
TI - Activity of Escherichia coli DNA-glycosylases on DNA damaged by methylating and
ethylating agents and influence of 3-substituted adenine derivatives.
AB - Methylating and ethylating agents are used in the chemical industry and produced
during tobacco smoking. They generate DNA base damage whose role in cancer
induction has been documented. Alkylated bases are repaired by the base excision
repair pathway. We have established the repair efficiency of methylated and
ethylated bases by various Escherichia coli repair proteins, namely 3
methyladenine-DNA-glycosylase I (TagA protein), which excises 3-methyladenine and
3-methylguanine, 3-methyladenine-DNA-glycosylase II (AlkA protein), which has a
broad substrate specificity including 3- and 7-alkylated purines and the
formamidopyrimidine(Fapy)-DNA-glycosylase (Fpg protein) repairing imidazole ring
opened 7-methylguanine. The comparison of the Km values of these various enzymes
showed that methylated bases were excised more efficiently than ethylated bases.
Several 3-alkyladenine derivatives have been synthesized and examined for their
ability to inhibit the activity of the various repair proteins. We have shown
that 3-ethyl-, 3-propyl-, 3-butyl- and 3-benzyladenine were much more efficient
inhibitors of TagA protein than 3-methyladenine. The inhibitory effect was
increased with the increase of the size of alkyl-group and IC50 for 3
benzyladenine was 0.4 +/- 0.1 microM as compared to 1.5 +/- 0.3 mM for 3
methyladenine. These compounds inhibited neither the AlkA protein nor human 3
methyladenine-DNA-glycosylase (ANPG protein). Moreover, 3-hydroxyethyladenine did
not affect the activity of any of these enzymes. Taken together, these results
suggest that hydrophobic interactions are involved in the mechanism of inhibition
and/or recognition and excision of alkylated purines by TagA protein.
PMID- 9637246
TI - Requirement for DNA mismatch repair proteins in the transcription-coupled repair
of thymine glycols in Saccharomyces cerevisiae.
AB - Defects in DNA mismatch repair have been shown to lead to increased genomic
instability and mutability. We recently found that human cells defective in the
DNA mismatch repair gene, hMSH2, were deficient in the transcription-coupled
repair (TCR) of both oxidative DNA damage, including thymine glycols, and UV
induced DNA damage. However, in a hMLH1 mutant, only a reduction in the TCR of UV
damage was observed. In this study, we examined whether TCR of thymine glycols in
Saccharomyces cerecisiae also requires the genes involved in DNA mismatch repair.
We found that yeast cells containing mutations in MSH2 were deficient in the
removal of thymine glycols from the transcribed strand of the RPB2 gene, while
cells with mutations in either MLH1 or PMS1 alone showed near normal levels of
TCR of thymine glycols. Interestingly, double mutants in the MLH1 and PMS1 genes
were deficient in TCR of thymine glycols. Taken together, these results suggest
that these two MutL homologues can act independently of each other, but that they
have overlapping roles in TCR. Overall levels of thymine glycol removal were not
reduced in the mismatch repair mutants. In contrast to the results with thymine
glycols, no defects in TCR of pyrimidine dimers were found in cells with
mutations in MSH2, MLH1, PMS1, and MLH1/PMS1.
PMID- 9637247
TI - Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer
prone syndromes.
AB - Host-cell reactivation (HCR) of UV-C-irradiated herpes simplex virus type 1 (HSV
1) has been determined in skin fibroblasts from the following hereditary cancer
prone syndromes: aniridia (AN), dysplastic nevus syndrome (DNS), Von Hippel
Lindau syndrome (VHL), Li-Fraumeni syndrome (LFS) and a family with high
incidence of breast and ovarian cancer. Cells from AN, DNS or VHL patients were
found to exhibit heterogeneity in HCR. Cells from individuals belonging to an LFS
family show reduced HCR in all cases where the cells were derived from persons
carrying one mutated p53 allele, whereas cells derived from members with two wild
type alleles show normal HCR. LFS cells with reduced HCR also reveal reduced
genome overall repair, and a slower gene-specific repair of the active adenosine
deaminase (ADA) gene, but little if any repair of the inactive 754 gene. In the
breast/ovarian cancer family, reduced HCR is observed in skin fibroblasts derived
from both afflicted and unaffected individuals. In addition, these cells display
lower survival after exposure to UV-C and exhibit higher levels of SCEs than
those in normal cells. These observations indicate that various hereditary cancer
prone syndromes, carrying mutations in different tumor-suppressor genes, exhibit
an unexplained impairment of the capacity to repair UV-damaged DNA.
PMID- 9637248
TI - Minimal tRNA(Ser) and tRNA(Sec) substrates for human seryl-tRNA synthetase:
contribution of tRNA domains to serylation and tertiary structure.
AB - The recognition process of tRNA(Ser) and tRNA(Sec) by human seryl-tRNA synthetase
(SerRS) was studied using T7 transcripts representing defined regions of human
tRNA(Ser) or tRNA(Sec) and the influence of the tRNA elements on serylation and
tertiary structure was elucidated. The anticodon arms of both tRNAs showed no
contribution to serylation in contrast to the acceptor stems and the long extra
arms. D and T arms were only involved in formation of the L-shaped tRNA
structure, not in the recognition process between tRNAs and SerRS. This is the
first report of microhelices adapted from human tRNAs being aminoacylated by
their homologous synthetase.
PMID- 9637249
TI - P1,P4-diadenosine 5' tetraphosphate induces nitric oxide release from bovine
aortic endothelial cells.
AB - Since the infusion of P1,P4-diadenosine 5' tetraphosphate (Ap4A) into animal
models induces vasodilation [1,2], the present study was performed to determine
whether Ap4A induces the release of nitric oxide (NO) from endothelial cells.
Ap4A induced NO release was 4.2-fold greater than the amount of NO released under
basal condition. Ap4A induced NO release was inhibited by NG-nitro-L-arginine (L
NNA) and this inhibition was reversed by L-Arg. In addition, EGTA inhibits Ap4A
induced NO release. These data are consistent with Ap4A inducing the release of
NO from endothelial cells through the activation of endothelial nitric oxide
synthase.
PMID- 9637250
TI - Quantitative structure activity relationships for the conversion of
nitrobenzimidazolones and nitrobenzimidazoles by DT-diaphorase: implications for
the kinetic mechanism.
AB - Quantitative structure activity relationships (QSARs) for the conversion of
nitrobenzimidazolones and nitrobenzimidazoles by rat liver DT-diaphorase (EC
1.6.99.2) are described. The parameter used for description of the QSARs is the
energy of the lowest unoccupied molecular orbital (E(LUMO)) of the nitroaromatic
compounds. Interestingly, correlations with E(LUMO) were observed for both the
natural logarithm of kcat, but also for the natural logarithm of kcat/Km. The
minimal kinetic model in line with these QSARs is a ping-pong mechanism that
includes a substrate binding equilibrium in the second half reaction.
PMID- 9637251
TI - Human RanBP3, a group of nuclear RanGTP binding proteins.
AB - A group of novel human Ran-binding proteins, RanBP3, was identified using the
yeast two-hybrid system via Ran-mediated interaction with the nucleotide exchange
factor RCC1. Several open reading frames, representing putative alternatively
spliced products, were established by cDNA cloning. Two of them, RanBP3-a and
RanBP3-b, encode nuclear hydrophilic proteins of 499 and 562 amino acid residues.
The sequences contain FXFG motifs, characteristic of a subgroup of nucleoporins,
and a C-terminal domain showing similarity to the Ran-binding protein RanBP1.
These proteins are localized in the nucleus, preferentially bind RanGTP and may
be nuclear effectors of the Ran pathway.
PMID- 9637252
TI - Enhancement of transcriptional activity of T7 RNA polymerase by guanidine
hydrochloride.
AB - T7 RNA polymerase shows an increase in processive transcription in the presence
of low concentrations of guanidine hydrochloride (GdnCl) upto 60 mM, which is not
observed when the enzyme is treated with urea. Higher concentrations of the
denaturant lead to a progressive loss in the processive transcriptional activity
of the enzyme. We have attempted to explain the above phenomenon in terms of the
structural change in the enzyme. Fluorescence and CD studies suggest that the
tertiary structure of the native enzyme undergoes an alteration upon addition of
low concentration of guanidine hydrochloride. This is also indicated from the
decreased susceptibility of the enzyme to limited proteolysis by trypsin.
PMID- 9637253
TI - Effect of oxygen free radicals on myosin in muscle fibres.
AB - Experiments were performed on glycerol-extracted muscle fibres prepared from
psoas muscle of rabbit in the presence of hydroxyl free radical generating
system. Short irradiation of spin-labelled muscle fibres by UV light showed the
interaction of probe molecules with oxygen free radicals. The intensity of the
EPR signal from maleimide or isothiocyanate spin labels attached to the essential
thiol groups decreased following irradiation. Oxygen free radicals affected the
rate constant of the transition AM.ADP.Vi-->AM.ADP in the ATP hydrolysis cycle.
It was found that the essential -SH groups of myosin were involved in the
oxidation of sulphydryls by Ce(IV). Ce(IV) complexed to nitrilotriacetic acid in
the presence of spin trap produced long-lived free radicals located partly on SH
1 sulphydryls.
PMID- 9637254
TI - Biological dynamics and distribution of 3-hydroxy fatty acids in the yeast
Dipodascopsis uninucleata as investigated by immunofluorescence microscopy.
Evidence for a putative regulatory role in the sexual reproductive cycle.
AB - Dipodascopsis uninucleata has been recently shown to produce 3-hydroxy polyenoic
fatty acids from several exogenous polyenoic fatty acids. In order to examine
whether endogenous 3-hydroxy fatty acids (3-OH-FA) may be implicated in the
developmental biology of this yeast, we mapped by immunofluorescence microscopy
their occurrence in fixed cells with or without cell walls using an antibody
raised against 3R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (3R-HETE), the
biotransformation product from arachidonic acid (AA). This antibody turned out to
cross-react with other 3-OH-FA. 3-OH-FA were detected in situ in gametangia,
asci, as well as between released ascospores, and proved to be associated with
the sexual reproductive stage of the life cycle of the yeast. Acetylsalicylic
acid (1 mM), which is known to suppress the formation of 3-OH-FA from exogenous
polyenoic fatty acids, inhibited the occurrence of immunoreactive material as
well as the sexual phase of the life cycle suggesting a prominent regulatory role
of 3-OH-FA for the latter.
PMID- 9637255
TI - Characterization of the 3' end of the mouse SERCA 3 gene and tissue distribution
of mRNA spliced variants.
AB - The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) type 1 and 2 genes are
alternatively spliced at their 3' end. We hypothesized that similar mechanism may
occur for SERCA 3. Two spliced variants were identified by RNase protection
analysis. We then isolated and sequenced the 3' end portion of the mouse SERCA 3
gene, and confirmed the presence of an alternative mRNA transcript by sequencing
a cDNA fragment obtained by RT-PCR. Tissue distribution of the alternatively
spliced mRNAs was studied by RT-PCR: SERCA 3b was the only isoform expressed in
endothelial cells from aorta and heart and also was the major isoform in lung and
kidney whereas SERCA 3a and 3b were coexpressed in trachea, intestine, thymus,
spleen, and fetal liver.
PMID- 9637256
TI - Cdc42 is required for membrane dependent actin polymerization in vitro.
AB - In vitro actin based motility assays with bacterial pathogens have provided
powerful systems to both understand and dissect actin dynamics as well as cell
motility. Taking advantage of endogenous membrane vesicles in Xenopus extracts we
have developed an in vitro assay to study membrane dependent actin
polymerization. Our results demonstrate that membrane dependent actin
polymerization, in contrast to Listeria stimulated actin filament assembly, is
dependent on small GTPases of the Rho family. Using a combination of depletion
and reconstitution experiments we have shown that Cdc42 but not Rac or Rho is
required to stimulate actin polymerization from membranes. The in vitro system we
have described here is amenable to identification of the downstream effectors of
Cdc42 required for membrane dependent actin polymerization.
PMID- 9637257
TI - An intrinsically stable antibody scFv fragment can tolerate the loss of both
disulfide bonds and fold correctly.
AB - A fully functional cysteine-free derivative of the intrinsically stable anti-HER2
scFv fragment hu4D5-8 was generated by replacing the disulfide forming cysteine
residues in VH and VL with the amino acid combination valine-alanine in both
domains. The antigen binding properties, determined by ELISA and BIAcore
measurements, were not affected by removal of the disulfide bonds. The
thermodynamic stability of the disulfide-containing scFv of 8.1 kcal/mol is
decreased upon complete reduction of both disulfides to 2.7 kcal/mol, while that
of the valine-alanine variant is somewhat higher (about 3.8 kcal/ mol). Our
results suggest that, in principle, a disulfide-free fully functional derivative
of any scFv can be obtained, as long as the corresponding disulfide-containing
scFv has a high enough thermodynamic stability.
PMID- 9637258
TI - Unique chemical reactivity of His-21 of CRM-197, a mutated diphtheria toxin.
AB - CRM-197 is a mutated diphtheria toxin (63000 Da) widely used as a carrier protein
of conjugated vaccines. Among the 14 histidines of CRM-197, His-21 was found to
be modified selectively with iodoacetamide based reagents. This finding suggests
a simplified method for the preparation of conjugate vaccines crosslinked to CRM
197. A bifunctional iodoacetamide, N,N'-(2-hydroxy-1,3-propanediyl)-bis-12
iodoacetamidel (I-CH2-CONH-CH2-CH(OH)-CH2-NHCO-CH2-I) (HPBIA), was synthesized
and allowed to react with CRM-197. In the alkaline buffer of pH 8.0-8.4, HPBIA
was shown to react and intra-bridge His-21 and Lys-24 of CRM-197 sequentially. At
lower pH (7.1-7.5) in the phosphate buffer, the reactivity of Lys-24 toward HPBIA
was suppressed drastically. Under these conditions, His-21 could be specifically
labeled with HPBIA. Initial experiments have demonstrated that HPBIA modified CRM
197 is able to crosslink to a cysteine-containing peptide. These results offer a
potential route for improving the homogeneity of CRM-197 based protein-peptide as
well as protein-polysaccharide conjugates.
PMID- 9637259
TI - Lack of beta-amyloid production in M19 cells deficient in site 2 processing of
the sterol regulatory element binding proteins.
AB - The processing of the amyloid precursor protein (APP) and the sterol regulatory
element binding protein show remarkable analogies. Following a first lumenal
cleavage, both proteins undergo a cleavage within the transmembrane domain by
enzymatic activities named gamma-secretase and S2P, respectively. We analyzed the
processing of APP in the mutant Chinese hamster ovary (CHO) cell line M19 which
lacks the S2P gene encoding for a putative metalloprotease. In these cells, we
were not able to detect any beta-amyloid production from endogenous or
transiently overexpressed APP, although the transport of APP along the secretory
pathway, its processing by alpha- and beta-secretase, as well as its secretion
were normal. This strongly suggests that the gamma-secretase cleavage in M19
cells is severely impaired.
PMID- 9637260
TI - Distinct phospholipase C-regulated signalling pathways in Swiss 3T3 fibroblasts
induce the rapid generation of the same polyunsaturated diacylglycerols.
AB - Prostaglandin F2alpha, platelet-derived growth factor (PDGF) and calcium
ionophore A23187 stimulated the rapid (within 25 s) generation of polyunsaturated
1,2-diacylglycerol (DAG) species, in particular 18:0/20:3n-9, 18:0/20:4n-6 and
18:0/20:5n-3, in Swiss 3T3 fibroblasts. This was followed by a second sustained
phase characterised by saturated, monounsaturated and diunsaturated DAG species
derived, at least partially, from a phospholipase D/phosphatidate
phosphohydrolase-linked pathway. This could be directly activated by phorbol
ester. Assay of rat brain protein kinase C (PKC) in lipid vesicles showed that
first phase, polyunsaturated-enriched DAG isolated from Swiss 3T3 cells was a
more potent activator of kinase activity compared to that achieved with DAG from
control or 5 min stimulated cells. Thus activation of distinct members of the
phospholipase C family leads to the rapid and almost identical generation of
polyunsaturated DAG species which are capable of preferentially activating
protein kinase C (PKC).
PMID- 9637261
TI - Identification of lysine-238 of Escherichia coli biotin carboxylase as an ATP
binding residue.
AB - Escherichia coli biotin carboxylase was affinity labeled with adenosine
diphosphopyridoxal to identify its ATP binding site. Lysyl endopeptidase
digestion of the modified protein, followed by high performance liquid
chromatography separation and amino acid sequencing allowed to identify lysine
238 to be the site of modification. Site-directed mutagenesis of this residue
into alanine, arginine or glutamine resulted in mutants with much decreased
activity. Lysine-238 seems to interact with the gamma-phosphate group of ATP but
is not involved in catalysis.
PMID- 9637262
TI - Imidazolium crosslinks derived from reaction of lysine with glyoxal and
methylglyoxal are increased in serum proteins of uremic patients: evidence for
increased oxidative stress in uremia.
AB - Glyoxal (GO) and methylglyoxal (MGO) are reactive dicarbonyl compounds formed
during autoxidation of both carbohydrates and lipids. They may react with lysine
and arginine residues of proteins in Maillard or browning reactions, yielding
advanced glycation or lipoxidation end products. Among these are the imidazolium
crosslinks, N,N(-di(N(epsilon)-lysino))imidazolium (glyoxal-lysine dimer, GOLD)
and N,N(-di(N(epsilon)-lysino))-4-methyl-imidazolium (methylglyoxal-lysine dimer,
MOLD). We have detected and measured GOLD and MOLD in human serum by electrospray
ionization/mass spectrometry/mass spectrometry (ESI/MS/MS), using 15N4-GOLD and
15N4-MOLD as internal standards. In this report we show that levels of GOLD and
MOLD are significantly elevated (3-4-fold, P< 0.01) in sera of non-diabetic
uremic patients, compared to age-matched controls, and represent a major class of
non-enzymatic, Maillard reaction crosslinks in plasma proteins. These results
provide strong evidence for increased non-enzymatic crosslinking of tissue
proteins by GO and MGO in uremia, implicating oxidative stress and resultant
advanced glycation and lipoxidation reactions in tissue damage in uremia.
PMID- 9637263
TI - Epstein-Barr virus strain characterization.
AB - The Epstein-Barr virus (EBV), a ubiquitous human herpesvirus originally described
in cultured lymphoblasts from African Burkitt's lymphoma, is the causative agent
of infectious mononucleosis, but appears to be involved in the pathogenesis of a
variety of diseases. EBV has the ability to establish lifelong persistent
infection, where only a restricted pattern of the viral proteins is expressed.
Periodic reactivation of EBV occurs, where mature EBV particles are produced.
Strain variation is potentially important in the biology and epidemiology of EBV,
and in attempts to relate EBV to associated diseases. Analysis of the EBV genomes
isolated from patients with EBV-associated diseases and from various parts of the
world has so far failed to identify conclusive disease-specific viral subtypes.
This review focuses on the different strategies which have been used for strain
characterization or subtyping of EBV.
PMID- 9637264
TI - Clinical microbiology laboratories do not always detect resistance of Haemophilus
influenzae with disk or tablet diffusion methods. Finnish Study Group for
Antimicrobial Resistance (FiRe).
AB - The performance of disk diffusion testing of Haemophilus influenzae was evaluated
in 20 laboratories. Thirteen disk-medium-breakpoint-inoculum modifications were
used in Finnish clinical microbiology laboratories. The performance of various
methods was evaluated by testing a susceptible control strain and one with non
beta-lactamase-mediated ampicillin resistance 10 times in 16 laboratories. Gaps
in millimeters were measured between these two groups of results. The strains
were separated by a gap of at least 5 mm in 8/16 laboratories testing ampicillin,
in 7/15 laboratories testing cefaclor, in 5/ 16 laboratories testing cefuroxime,
and in 15/16 laboratories testing trimethoprim-sulfa. Detection of ampicillin
resistance was better with 2.5 microg tablets than with 10 microg disks or 33
microg tablets. For MIC-determinations, 785 isolates and their disk diffusion
results were collected. None of the 12 clinical isolates with non-beta-lactamase
mediated ampicillin resistance was detected as resistant in the participating
laboratories. The ampicillin and cefaclor results of the isolates were no better
even when a laboratory was able to separate the control strains. Cefaclor results
were unreliable because of poor disk diffusion-MIC correspondence and incoherent
breakpoint references. Interlaboratory variation of the zone diameters caused
false intermediate results of cefuroxime-susceptible strains. When ampicillin,
cefaclor and cefuroxime were tested, the discrimination of laboratories using
disks and tablets was equal, whereas the laboratories using paper disks were
better able to detect trimethoprim-sulfa resistance.
PMID- 9637265
TI - Adherence of Staphylococcus aureus, Klebsiella pneumoniae and Candida albicans to
human buccal epithelial cells, from healthy persons and HIV carriers, under the
influence of Broncho Vaxom in vitro and ascorbic acid in vivo.
AB - We examined the in vitro effect of Broncho Vaxom (BV) (an immunobiotherapeutic
preparation containing a lysate made from bacteria often involved in respiratory
tract infections) on adherence of Staphylococcus aureus, Klebsiella pneumoniae
and Candida albicans to human buccal epithelial cells (BEC) of healthy volunteers
and HIV carriers. We also examined the ex vivo effect of ascorbic acid on the
adherence of the same microorganisms to BEC of HIV carriers. The study reached
the following conclusions: The presence of BV in vitro significantly reduces the
adherence of the tested strains to BEC from healthy persons and HIV carriers. No
significant difference was observed between healthy persons and HIV carriers
regarding the adherence of the tested strains to BEC. Significant difference in
the adherence of the tested strains to BEC was observed between HIV carriers who
had been taking ascorbic acid over a 3-month period and those who had not. There
was no further reduction in the adherence of the tested strains to BEC from HIV
carriers who had been taking ascorbic acid in the presence of BV in vitro.
PMID- 9637266
TI - Expression of bcl-2 in fetal thymus, thymomas and thymic carcinomas. Association
with p53 expression and review of the literature.
AB - Bcl-2 is a proto-oncogene inhibiting apoptosis, and p53 is a tumor supressor gene
which induces apoptosis. Both seem to take part in tumorigenesis. An inverse
relationship between the two genes has been reported in some neoplasms, although
the exact mechanism is not fully understood. We have analyzed the expression of
bcl-2 and p53 in 18 fetal thymuses and 18 clinically benign and malignant
thymomas: bcl-2 was expressed by most medullary lymphocytes and epithelial cells
of the normal thymus; p53 was not expressed at all. Bcl-2 and p53 were co
expressed in the majority of the thymomas and the staining reaction was stronger
in the clinically malignant ones. It is concluded that although co-expression of
bcl-2 and p53 is of doubtful prognostic relevance, the staining pattern of bcl-2
supports the histogenetic classification system of Muller-Hermelink.
PMID- 9637267
TI - Ribotyping of Pseudomonas aeruginosa from infected patients: evidence of common
strain types.
AB - Sixty-nine strains of Pseudomonas aeruginosa isolated from infected patients at
three hospitals in Valencia were serotyped and analyzed by comparison of
restriction fragment length polymorphisms of ribosomal RNA genes (ribotyping).
Genomic Southern blots of EcoRI restriction digests were hybridized with a
universal rRNA gene probe from Escherichia coli 16S and 23S rRNA. Strains were
genetically diverse and 12 different ribotypes of 2 to 7 bands between 5 and 21.5
kb were defined. All strains shared a common band of 6.0 kb. The predominant
ribotypes were R1 and R2, representing 25% and 41% of all isolates, respectively.
Ribotypes were not consistently associated with serotypes, but they clearly
subtyped strains of the same serotype. This study demonstrated the prevalence of
certain strain types associated with infected patients at Valencia hospitals,
confirming the high typability and reproducibility of a single enzyme ribotyping
for epidemiological studies of Pseudomonas aeruginosa. Ribotyping could be
particularly useful if used in conjunction with serotyping.
PMID- 9637268
TI - Immunohistochemical determination of tumor angiogenesis measured by the maximal
microvessel density in human prostate cancer.
AB - Tumor growth beyond a certain size requires angiogenesis. Experimental evidence
shows that once tumors leave the pre-angiogenic phenotype to become angiogenic,
metastases often start to evolve. The aim of this study was to develop a
reproducible immunohistochemical technique and method to characterize the
neovascularization in archival prostate cancer tissue by quantifying the
microvessel density (MVD). Archival tumor specimens from 64 consecutively
diagnosed prostate cancer patients were immunostained for von Willebrand Factor
(vWF), endothelial antigen and for CD31 combined with the use of different
digestive enzymes (trypsin and pronase) and heating in a microwave oven. Both the
mean and the maximal MVD, and the reproducibility of the method were estimated.
Finally, the mean MVD, the maximal MVD, and clinical characteristics were
correlated with the crude survival of the patient population. The
immunohistochemical staining for vWF to measure the maximal MVD was found to be a
reproducible method of characterizing the individual tumor. Both a univariate and
a multivariate analysis demonstrated that the maximal MVD, in contrast to the
mean MVD, was significantly associated with survival in prostate cancer patients.
We conclude that evaluation of angiogenesis by immunostaining the endothelial
cells for vWF measured by the MVD in the most vascularized areas of the tumor is
a reproducible method of characterizing the individual prostate tumor. Maximal
MVD proved to be an independent prognostic parameter useful in conjunction with
other known prognostic markers in human prostate cancer.
PMID- 9637269
TI - HIV infection in the first heart transplantation in Italy: fatal outcome. Case
report.
AB - A 46-year-old man with alcoholic dilated cardiomyopathy underwent heart
transplantation on November 14, 1985. It was the first cardiac transplant in
Italy and at that time no HIV antibody screening test was available in this
country. The patient remained in good health for 6 years postoperatively, with
only one episode of rejection (type 3A). In June 1992 he died of fulminant
complications of AIDS and severe chronic rejection. Neither the patient nor the
organ donor belonged to any of the known risk groups for HIV infection; a
retrospective analysis revealed that perioperative blood transfusions had been
the vectors of transmission.
PMID- 9637270
TI - Experimental porcine neosporosis.
AB - Six gilts were inoculated intramuscularly with 2.5x10(6) tachyzoites of Neospora
caninum on three different days of gestation to study the pathogenic effect of
Neospora infection in pigs, including possible transplacental transmission. The
gilts were euthanized 59, 30, and 9/10 days postinoculation (p.i.), corresponding
to days 107, 102/106 and 110/111 of pregnancy. With the exception of one animal
(euthanized day 9 p.i.) all gilts seroconverted as measured by the indirect,
fluorescent antibody test (IFAT). Neosporosis with multifocal intralobular
necrotizing hepatitis was seen in the two gilts inoculated 9/10 days before
euthanasia. The uterus of one gilt inoculated 59 days before euthanasia revealed
granulomatous and focal necrotizing endometritis with a corresponding multifocal
necrosis of the trophoblasts of two fetuses. Transplacental neosporosis was
indicated in the two fetuses by strongly elevated Neospora IFAT titres in pleural
fluid and by the presence of multifocal necrotizing encephalitis and hepatitis
together with non-suppurative myocarditis, pneumonitis, nephritis and hepatitis.
Furthermore, N. caninum was re-isolated in cell culture from one of these
fetuses. A third fetus from the same gilt revealed only disseminated, pinpoint
necroses in the liver. Immunohistochemically, N. caninum tachyzoites were
detected in association with histopathological changes in the liver and the
endometrium of the gilts, and in the brain, liver, and allantochorion of the
three fetuses.
PMID- 9637271
TI - Identification of Prototheca from bovine mastitis in Denmark.
AB - In the present study, algal isolates recovered during the period 1991 through
1996 from Danish cases of bovine mastitis were characterized and identified.
Sixteen isolates of Prototheca were obtained, all of which were identified as
Prototheca zopfii according to assimilation pattern, absence of capsules and
resistance to clotrimazole.
PMID- 9637272
TI - Immunoreactivity of pleural malignant mesotheliomas to glutathione S
transferases.
AB - Malignant mesotheliomas show a highly variable aggressiveness, but it is
difficult to predict the outcome in the individual case at the time of diagnosis.
Glutathione S-transferases are detoxification enzymes that have been correlated
with the prognosis in some tumours. We have therefore assessed the value of GST
expression as a prognostic parameter in mesotheliomas. The reactivities to GST
pi, -alpha and -mu antibodies were studied in histological sections from
altogether 88 cases. Most of them showed distinct cytoplasmic reactivity to one
or more of the GST antibodies tested. This high prevalence is in good agreement
with the low responsiveness of mesotheliomas to chemotherapy. However, there was
no prognostic value in detecting GST immunoreactivity, and it gave no information
of value for distinguishing between neoplastic and reactive mesothelium.
PMID- 9637273
TI - A histomorphometric study of haematological disorders with respect to marrow
fibrosis and osteosclerosis.
AB - A retrospective investigation of 75 EDTA-decalcified Jamshidi biopsies collected
over a 2-year period at Aarhus University Hospital was performed. The biopsies
originated from 75 patients suffering from idiopathic myelofibrosis, other
chronic myeloproliferative disorders, or other conditions with known associations
with bone marrow fibrosis. The relative volumes of trabecular and woven bone, as
well as haematopoietic and non-haematopoietic tissue, were estimated
histomorphometrically. The degree of fibrosis was estimated semiquantitatively.
Finally, the thickness of trabecular osteons was estimated from the number of
lamellae by counting. Patients with idiopathic myelofibrosis had statistically
significantly more bone tissue than the other groups of patients. The
osteosclerosis was primarily due to woven bone. Larger cancellous osteons also
suggested a positive balance in bone remodelling. The amount of bone tissue
showed furthermore a statistically significant increase through the groups of
polycythaemia vera, essential thrombocythaemia, chronic myelogenous leukaemia and
idiopathic myelofibrosis. Parallel to the increase in the amount of bone, an
increase in the degree of marrow fibrosis was detected. The positive correlation
between the amount of bone and the degree of marrow fibrosis was statistically
highly significant (p=0.0008).
PMID- 9637274
TI - Evaluation of infectious etiology in subacute thyroiditis--lack of association
with coxsackievirus infection.
AB - The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it
is postulated to be associated with viral infections and genetic factors. In the
present study, the possibility of an infectious etiology was prospectively
studied in 27 consecutive patients with SAT. Special emphasis was put on the role
of enteroviruses. Coupled sera (interval one month) were taken from all patients
and single sera from 29 control subjects for virus antibody determinations. Stool
samples were collected for virus isolation and fine-needle aspiration samples
from thyroid gland for the detection of enterovirus RNA using RT-PCR were taken
from SAT patients. Enteroviral antibodies were tested using three different
methods: indirect EIA, heavy chain capture RIA, and standard complement fixation
(CF) test. Antibodies against other common viral pathogens, including
enteroviruses, were screened using the CF test and those against Mycoplasma
pneumoniae and Chlamydia pneumoniae using EIA and microimmunofluorescence
techniques, respectively. Common respiratory viruses were also screened from
nasopharyngeal suction samples by antigen detection EIA. Based on serological
findings, one patient had acute Cytomegalovirus infection. All other patients
were negative in antibody tests, virus isolation, RT-PCR, and antigen detection.
Enterovirus RNA was not detected by PCR in the thyroid tissue in any of the fine
needle aspiration samples. There was no evidence of recent enteroviral infections
in SAT patients. The results suggest that SAT is not usually associated with
acute infections. No evidence was obtained to support the proposed role of
enteroviruses as an important etiologic agent of SAT.
PMID- 9637275
TI - Radionuclide cancer therapy.
AB - Therapeutic nuclear medicine is rapidly developing as an additional treatment
modality in oncology. Its unique characteristics are the systemic, yet selective
delivery of radiation doses in target tissues, its non-invasiveness, the relative
lack of immediate and late side effects, and the advantage that uptake and
retention in the tumor can be pre-assessed by tracer studies. Many different
tumor seeking radiopharmaceuticals are being used for therapy by different routes
and a variety of targeting mechanisms. The current clinical role of radionuclide
therapy is briefly reviewed, as well as more general aspects and considerations,
such as mechanisms for tumor targeting, the choice of radionuclide labels,
radiopharmacy, drug delivery, radiation protection, dosimetry and toxicity.
PMID- 9637276
TI - Rapid data acquisition protocol in ECG-gated myocardial perfusion SPECT with Tc
99m-tetrofosmin.
AB - Into 25 patients with heart disorders, 99mTc-tetrofosmin 555-740 MBq was injected
intravenously at rest. After 40 minutes, ECG-gated myocardial perfusion SPECT was
performed with a two detector gamma camera VERTEX (ADAC), setting up two
detectors to form a 90-degree angle. Sixteen frames per R-R interval were
acquired during a 180 degree rotation from the RAO 45 degrees to the LPO 45
degrees. A pair of data sets with standard (SDA) and rapid data acquisition (RDA)
protocols was collected. In an SDA protocol, SPECT imaging was performed for 50
sec per step in 5 degree angular steps (total acquisition time; 15 minutes). An
RDA protocol was conducted with 12 sec per step, 6 degree angular steps
(acquisition time, 3 minutes). LVEF (%) and LVEDV (ml) quantitated automatically
with a QGS program showed excellent correlations between two protocols with
correlation coefficients of 0.980 (p < 0.01) and 0.983 (p < 0.01), respectively.
Subsequently visual assessment of regional wall motion based on a four-point
grading system was carried out with a 3-D cine LV display. High complete
agreement was gained with 158 (90.3%) out of total 175 segments, so that
assessment of the global and regional LV function with the RDA protocol
demonstrated high reliability and feasibility.
PMID- 9637277
TI - The evolutional stage changes in sarcoidosis on gallium-67 scintigraphy.
AB - Gallium-67 scintigraphy has been proven as the imaging modality of choice in
monitoring the presence of active disease in sarcoidosis. The purpose of this
study is to analyze the patterns of evolutional stage changes of sarcoidosis
while on steroid therapy by Ga-67 scintigraphy. METHODS: Eighty-six consecutive
patients with biopsy-proved sarcoidosis are evaluated by Ga-67 scintigraphy.
Thirty-six of 86 patients have had a baseline and one to eight follow-up Ga-67
scintigraphs (total 136 studies). The initial follow-up scintigraphs are obtained
on average about 4-12 months after the baseline study. RESULTS: Seventeen of 36
patients (47.2%) are in stage IV at the time of the baseline study. Following
their first course of corticosteroid therapy, 13 patients remained in the same
stage and activity distribution pattern while 13 patients have shown reversion to
other stages, eight patients showed complete remission while two patients became
active from inactive stage. CONCLUSION: Evolutional stage changes are seen in 23
patients (63.9%), including eight patients (22.2%) who showed complete
scintigraphic remission. The evolutionary stage changes remain quite variable and
unpredictable. This, however, should not detract from the usefulness of Ga-67
scintigraphy in the diagnosis and prognostic evaluation of sarcoidosis,
particularly when extrapulmonary involvement (Stage IV disease) is present.
PMID- 9637278
TI - Localization of colorectal carcinoma by rhenium-188-labeled B72.3 antibody in
xenografted mice.
AB - In order to evaluate the feasibility of 188Re-labeled antibodies for
radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on
the surface membranes of colorectal cancer cells, was directly labeled with
188Re, obtained from a 188W/188Re generator, using stannous tartrate and compared
with 125I-labeled B72.3. As a control, a human IgG was also radiolabeled with
188Re and 125I. Prepared antibodies for 188Re labeling could be stored as kits.
Biodistribution was determined in nude mice inoculated with human colorectal
carcinoma LoVo. Labeling efficiency and immunoreactivity of 188Re-B72.3 were
80.3% and 64.7%, respectively. 188Re-B72.3 localized specifically in the LoVo
tumors. Although the absolute tumor accumulation level of 188Re-B72.3 was lower
than 125I-B72.3, 188Re-B72.3 demonstrated higher tumor-to-blood contrast than the
125I-labeled counterpart, 2.04 +/- 0.44 vs. 1.05 +/- 0.28 at 96 hours, because of
fast clearance from the blood. 188Re-B72.3 seemed efficient for the imaging and
therapy of colorectal carcinoma.
PMID- 9637279
TI - Clinical significance of reduced cerebral metabolism in multiple sclerosis: a
combined PET and MRI study.
AB - Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has
provided major insights into the disease's natural history, and many studies have
focussed on possible correlations between MRI findings and the clinical
manifestations of MS. In contrast, there are few reports on possible
relationships between functional imaging data and cognitive function. The present
study assessed the relationship between clinical presentation and combined
anatomical and functional imaging data in MS. Twenty patients with definite MS
underwent MRI and positron emission tomography (PET) to evaluate cerebral blood
flow (rCBF) and oxygen metabolism (rCMRO2). The relationships between these
neuroimaging findings and clinical data, including the Expanded Disability Status
Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time,
were evaluated with Spearman's rank correlation coefficients. A general reduction
in rCBF and rCMRO2 in the gray and white matter were found in the MS patients.
EDSS was correlated with the number and size of the lesions on MRI and was
negatively correlated with rCMRO2. A correlation between the decrease in rCMRO2
and the level of cognitive impairment was also found. The severity of cerebral
hypometabolism was also related to the number of relapses. Morphological and
functional findings obtained by MRI and PET are closely related to the clinical
status in MS. Our results suggest that measurement of cerebral metabolism in MS
has the potential to be an objective marker for monitoring disease activity and
to provide prognostic information.
PMID- 9637280
TI - Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy:
assessment by F-18-FDG PET study.
AB - In an investigation of myocardial metabolic abnormalities in hypertrophic
myocardium, the myocardial glucose metabolism was evaluated with F-18
fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with
hypertrophic cardiomyopathy, and the results were compared with those in 9
patients with hypertensive heart disease. F-18-FDG PET study was performed in the
fasting and glucose-loading states. The myocardial regional %dose uptake was
calculated quantitatively. The average regional %dose uptake in the fasting state
in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic
cardiomyopathy was significantly higher than that in the patients with
hypertensive heart disease (0.75 +/- 0.34%, 0.65 +/- 0.25%, and 0.43 +/-
0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in
the glucose-loading state in the patients with asymmetric septal hypertrophy and
dilated-phase hypertrophic cardiomyopathy was not significantly different from
that in patients with hypertensive heart disease (1.17 +/- 0.49%, 0.80 +/- 0.44%
and 0.99 +/- 0.45%, respectively). The patients with apical hypertrophy had also
low %dose uptake in the fasting state (0.38 +/- 0.21%) as in the hypertensive
heart disease patients, so that the characteristics of asymmetric septal
hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be
high FDG uptake throughout the myocardium in the fasting state. Patients with
apical hypertrophy are considered to belong to other disease categories
metabolically. F-18-FDG PET study is useful in the evaluation of the
pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy.
PMID- 9637281
TI - Gallium-67 scintigraphy in the treatment and prognosis of acute adult T-cell
lymphoma.
AB - The case of a 77-year-old male patient who complained of left upper quadrant pain
and progressive vomiting. Laboratory examination showed extremely high lactic
acid dehydrogenase (LDH) and adult T-cell leukemia antibody (ATLA). The
anatomical studies CT, MRI, US and upper GI series substantiated an omental
lymphadenopathy which was causing a circumferential compression of portions of
the duodenum and jejunum. Gallium-67 citrate (Ga-67) scintigraphy showed high
uptake at LUQ. Ultrasound guided biopsy failed to confirm the diagnosis.
Irradiation was performed. Ga-67 scintigraphy had a contributory role in clinical
subtyping of the disease, planning of treatment, posttreatment assessment and
prognostication of adult T-cell lymphoma.
PMID- 9637282
TI - Spectral analysis applied to dynamic single photon emission computed tomography
studies with N-isopropyl-p-(123I)iodoamphetamine.
AB - This study was performed to evaluate the usefulness of spectral analysis (SA)
applied to dynamic single photon emission computed tomography studies with N
isopropyl-p-(123I)iodoamphetamine (IMP). The unidirectional clearance of IMP from
the blood to the brain tissue (K1) obtained by SA (y (ml/g/min)) agreed well with
that obtained from a two-compartment model using the nonlinear least-squares
(NLSQ) method (x (ml/g/min)) (y = 0.994x + 0.003, r = 0.999, standard error of
the estimate (SEE) = 0.005 ml/g/min). The rate constant for back diffusion of IMP
from the brain tissue to the blood (k2) obtained by SA (y (min(-1))) also agreed
well with that obtained by the NLSQ method (x (min(-1))) (y = 0.985x + 0.000, r =
0.948, SEE = 0.001 min(-1)). The brain vascular volume (V0) obtained by SA (y
(ml/g)) correlated well with that obtained by the NLSQ method (x (ml/g)) (y =
1.138x + 0.000, r = 0.867, SEE = 0.012 ml/g). These results indicate that SA is
applicable and useful for quantification of the kinetic parameters of IMP in the
human brain, and can be an alternative approach to compartment analysis.
PMID- 9637283
TI - Imaging of intraperitoneal tumors with technetium-99m GSA.
AB - 99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a
receptor-binding agent for the assessment of liver function. The aim of this
study was to investigate the usefulness of 99mTc-GSA in intraperitoneal (i.p.)
tumor imaging. A tumor model was established by i.p. inoculating nude mice with
human ovarian cancer cell SHIN-3, or colon cancer cell LS 180. Radiolabels were
i.p. injected into the tumor-bearing mice and the biodistribution of
radioactivity was examined. After administration, 99mTc-GSA rapidly accumulated
in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the
injection. Radioactivity in the blood was very low, less than 0.3 %ID/g,
resulting in high tumor-to-blood ratio. Tumors could be clearly seen by
scintigraphic imaging. Accumulation of i.p.-injected 99mTc labeled human serum
albumin (HSA) in i.p. tumors was similar to that of 99mTc-GSA, but radioactivity
of 99mTc-HSA in the circulation was high, resulting in a significantly lower
tumor-to-blood ratio. In conclusion, 99mTc-GSA, when i.p. injected, accumulated
in i.p. tumors and cleared from circulation rapidly, which would make it useful
for the imaging of i.p. tumors.
PMID- 9637284
TI - Data base and management system for clinical positron emission tomography (PET)
studies.
AB - A data base and management system connected to an image analysis system has been
developed and utilized for clinical positron emission tomography (PET). This data
base system, 1) is based on "GBASE", a general purpose data base, which runs on a
UNIX work station, 2) works on a network file system and is connected to PET
cameras and other data acquisition devices as well as to an image analysis system
"Dr.View", 3) centrally manages the data stored in a data storage unit, 4) is
easily modifiable and expandable, and 5) has a human friendly interface which
requires minimum operation for registration, retrieval and management. We have
been using this system to handle clinical PET data for seven years and have
optimized the data base schema. As a result, this system has become a truly
practical tool for the daily operation and is well-received by technologists,
nuclear physicians and attending physicians.
PMID- 9637285
TI - Differences in intestinal length between specific-pathogen-free (SPF) and
conventional swine.
AB - The length of the small intestine, cecum, and the rest of the large intestine of
specific-pathogen-free (SPF) swine was compared with that of conventional swine.
The average length of the small intestine of SPF swine was shorter than that of
conventional swine. The difference was significant for female SPF swine. There
was no difference between SPF and conventional swine in the length of the cecum,
colon and rectum.
PMID- 9637286
TI - Expression of growth factor ligand and their receptor mRNAs in bovine ova during
in vitro maturation and after fertilization in vitro.
AB - We analyzed the expression of mRNAs for growth factor [epidermal growth factor
(EGF), insulin-like growth factor-I (IGF-I), basic fibroblast growth factor
(bFGF) and platelet-derived growth factor A chain (PDGF-A)] and their receptor
(R) by reverse transcription-polymerase chain reaction in bovine ova during
oocyte maturation in vitro (0-21 hr) and after fertilization in vitro (6-144 hr:
zygotes to blastocysts). Transcripts for EGF were not found before fertilization.
Transcripts for IGF-I were present in immature oocytes immediately after
collection and in embryos from the 2-cell stage onward. Transcripts for bFGF were
present in all stages of oocyte maturation and after fertilization up to the 16
cell stage. Transcripts for PDGF-A were present in all stages of oocyte
maturation and after fertilization up to the 2-cell stage. Transcripts for ErbB3
(a member of the EGF-R subfamily), and bFGF-R were present in all stages of
oocyte maturation, after fertilization up to the 2-cell stage, and the blastocyst
stage. Transcripts for IGF-I-R and PDGF-Ralpha were present in all stages of
oocyte maturation and embryo development. The results of this study showed that
eight different messages for growth factor and their receptor were detectable in
bovine ova during oocyte maturation and/or after fertilization in vitro and their
expression patterns were the gene-specific rather than the developmental stage of
bovine ova.
PMID- 9637287
TI - Dual infection with enterotoxigenic Escherichia coli and porcine reproductive and
respiratory syndrome virus observed in weaning pigs that died suddenly.
AB - Diarrhea, sudden death after short duration of diarrhea and sudden death without
apparent signs were observed in a herd of breeder pigs. Five pigs that died
suddenly with diarrhea (SDD pigs) and 6 pigs that died suddenly without signs (SD
pigs) were examined. The average age of the pigs was about 28 days. Twelve pigs
of age 10 to 14 days old showing diarrhea (D pigs) were also examined. Eleven of
them recovered. Large numbers of Escherichia coli were detected in all organs of
every SDD and SD pig and in feces of D pigs. All of the isolates were identified
as enterotoxigenic E. coli (ETEC) by the polymerase chain reaction (PCR). Porcine
reproductive and respiratory syndrome (PRRS) virus cDNA was also detected from
the lung of every SD and SDD pig by the RT-PCR. High and low titers of antibodies
to PRRS virus were found in 10-day-old and 1-month-old pigs, respectively. In an
experiment, 3 ETEC were isolated from 9 healthy weaning pigs during the quiescent
stage in the herd. These data showed that growth of the ETEC was not active in
healthy weaning pigs; however, following infection with PRRS virus ETEC infection
became systemic and caused peracute death in the weaning pigs. It suggested also
that infection with PRRS virus in 10-day-old pigs were protected by the colostral
antibodies, and fatal infection by ETEC did not occur as a result.
PMID- 9637288
TI - Identification of B cell epitopes of a 30 kDa Babesia equi merozoite surface
protein.
AB - A 30 kDa immunodominant surface antigen (p30) of Babesia equi has been used as a
diagnostic antigen. The B cell epitopes on this molecule recognized by horse sera
and monoclonal antibody (MAb) against p30, 36/133.97, were determined. A
synthetic peptide of p30 with amino acid sequence of 123FYQEVLFKGFEAV135
exhibited strong positive reaction with the infected horse sera. In contrast, MAb
36/133.97 recognized different region of p30, as peptide synthesized with amino
acid sequence of 27ASGAVVDFQLESI39 reacted strongly. In competitive inhibition
ELISA, the binding of MAb 36/133.97 to recombinant p30 was inhibited by horse
antibodies, although they did not recognize same or an overlapping epitope. The
data on B cell epitopes in this study may be important in improving
serodiagnostic methods of B. equi infection.
PMID- 9637289
TI - Bovine viral diarrhea virus replication in bovine follicular epithelial cells
derived from persistently infected heifers.
AB - Bovine follicle fluid and oocytes surrounded by follicular epithelial (FE) cells
were collected from ovaries of two heifers persistently infected with bovine
viral diarrhea virus (BVDV). BVDV was present in the follicle fluid at a higher
titer than in serum. The oocytes were matured in vitro under culture conditions
of 39 degrees C in humidified air containing 5% CO2. In vitro fertilization was
performed after 24 hr in culture (the day of insemination was defined as day 1),
and culture was continued through day 10. BVDV was present in the culture medium
at titers of 10(2.25) to 10(3.25) TC(I)D50/0.1 ml. The virus was also detected in
FE cells collected on day 10. Viral antigen was demonstrated in the cytoplasm of
FE cells by the indirect immunofluorescence technique. However, no BVDV was
detected in the embryos on day 10. These findings suggested that the oocytes or
embryos were unlikely to be infected with BVDV, but that the FE cells were
infected with BVDV and supported virus replication in cattle persistently
infected with BVDV.
PMID- 9637290
TI - Adhesive and bone resorptive activities of isolated osteoclasts from hen
medullary bone.
AB - In the present study, osteoclasts were isolated from hen medullary bones at the
formative and resorptive phases. The cells were cultured on glass culture dishes
and bone slices. After culturing, the adhesion activity of the isolated
osteoclasts with the substrates was estimated with a light microscope, and the
surfaces of the bone slices were observed with a scanning electron microscope.
The results showed that the adhesion activity of tartrate-resistant acid
phosphatase (TRAP)-positive osteoclasts is higher at the bone resorptive phase
than at the bone formative phase, and this tendency in isolated osteoclasts was
observed more frequently on the bone slices than on the glass culture dishes.
Furthermore, scanning electron microscopy showed that the isolated osteoclasts in
the bone resorptive phase adhered to the bone surface with developed-cytoplasmic
projections and formed broad pits where collagen fibrils were exposed. On the
other hand, isolated osteoclasts in the bone formative phase adhered to the bone
slice with board-shaped cytoplasmic projections and did not form any pits. These
results suggest that isolated osteoclasts in the bone resorptive phase have a
high level of adhesion activity and actively resorb the bone, whereas isolated
osteoclasts in the bone formative phase have a low level of adhesion activity and
cease bone resorption. The procedure reported here is useful for studying the
bone-resorptive mechanism of authentic osteoclasts.
PMID- 9637291
TI - Segregation of bovine viral diarrhea virus isolated in Japan into genotypes.
AB - It was suggested that 3 strains of bovine viral diarrhea virus (BVDV) isolated
from persistently infected calves in Tochigi prefecture in Japan belonged to BVDV
type II. It was recognized lack of PstI site on the 5'-untranslated region of
genome of them as well as BVDV type II reported previously. Inoculated with the 3
strains, the calves showed the mild decrease of platelet counts which was
specific clinical sign of BVDV type II. We should report that the 3 strains were
the first BVDV type II isolated in Japan. Neutralizing antibody titers of the
antisera against the 3 strains using laboratory strains as neutralizing virus
were lower than those of them using homologous strains. Therefore, it was
indicated that the difference between BVDV type I and BVDV type II in the
antigenicity.
PMID- 9637292
TI - Survey of Cryptosporidium oocysts from adult cattle in a slaughter house.
AB - Cryptosporidian oocysts were surveyed in rectal stools of adult cattle which were
carried into slaughterhouse from April 1995 to July 1996. We morphologically and
histologically investigated oocysts, and experimentally infected the isolated
oocysts to mice and rats. Cryptosporidian oocysts were detected from 24 of 512
cattle (4.7%). They were spherical or ovoid, and the size was 7.0-7.9 x 5.3-6.1
microm. Mice and rats inoculated orally with 10(5)-10(7) oocysts became infected
and discharged oocysts in the feces for a period of more than two months.
Developing parasites were detected from the stomach of mice, and not detected
from the other digestive tract. From these findings, present isolates from cattle
were identified as Cryptosporidium muris.
PMID- 9637293
TI - Field isolates of transmissible gastroenteritis virus differ at the molecular
level from the Miller and Purdue virulent and attenuated strains and from porcine
respiratory coronaviruses.
AB - The diversity in selected regions of the transmissible gastroenteritis virus
(TGEV) and porcine respiratory coronavirus (PRCV) genomes was analyzed among
known TGEV and PRCV strains and field isolates. The N-terminal half of the spike
(S) glycoprotein gene and open reading frames (ORF) 3, 3-1 and 4 were amplified
by reverse transcriptase reaction and polymerase chain reaction (RT/PCR), and
analyzed using restriction fragment length polymorphism (RFLP) patterns of the
amplified DNA. Reference TGEV strains (Miller and Purdue) and a PRCV strain (ISU
1), and TGEV and PRCV field isolates were analyzed. Based on the size of the ORF
3, 3-1 and 4 RT/PCR products, TGEV and PRCV strains could be quickly and easily
differentiated into three groups designated TGEV Miller, Purdue types and PRCV.
By RFLP analysis of the N-terminal region of the S glycoprotein gene and ORFs 3,
3-1 and 4, TGEV and PRCV strains were differentiated into five groups using the
restriction enzyme Sau3AI. Sequence analysis of a PCR product in the ORFs 3, 3-1
and 4 from virulent and attenuated Miller strains demonstrated additional
differences in that region which have been correlated with a change in virulence
of TGEV isolates.
PMID- 9637294
TI - Epitope mapping of bovine leukemia virus transactivator protein Tax.
AB - The immunogenicity of the bovine leukemia virus (BLV) transactivator protein
(tax) was studied by mapping its B-cell and T-cell epitopes. Peptides (18 to 20
mer) overlapping by 10 amino acids, spanning whole amino acid sequence of BLVtax
were synthesized. Recombinant BLVtax protein was used to immunize two different
strains of mice, C57BL/6 and BALB/c. B-cell and T-cell epitopes of recombinant
BLVtax protein was determined by screening all the 30 synthetic peptides, against
immune serum in ELISA for antibody reactivity, and against immune spleen cells in
lymphocyte proliferation assay for T-cell stimulation. Peptides with amino acids
at position 111-130 and 131-150 were T-cell epitopes for C57BL/6 and BALB/c mice
immune cells, respectively. B-cell epitope was mapped to amino acid sequence at
261-280 in both strains of mice. These results imply that BLVtax protein contains
some of BLV- immunodominant epitopes and this information may be applied for
designing an effective peptide vaccine capable of inducing neutralizing
antibodies as well as cellular immunity.
PMID- 9637295
TI - Changes in semen quality and in vitro sperm capacitation during various
frequencies of semen collection in dogs with both asthenozoospermia and
teratozoospermia.
AB - Eight male dogs with both asthenozoospermia and teratozoospermia were used in
this study. In experiment 1, semen was collected 10 times at intervals of 48 hr,
24 hr and 12 hr in 4 of the 8 dogs, and the semen quality was evaluated. In
experiment 2, semen was collected 5 times at 24-hr intervals in the other 4 dogs.
The spermatozoa collected on day 1 and day 5 were incubated for 4-6 hr in Canine
Capacitation Medium, and the percentages of hyperactivated sperm (%HA), acrosome
reacted sperm (%AR), and the zona pellucida-binding sperm count (ZP sperm count)
were assessed. The results of experiment 1 showed that the percentage of motile
sperm increased and the percentage of abnormal sperm decreased markedly as the
intervals between semen collections became shorter. When semen was collected at
12-hr intervals, the percentage of motile sperm increased from about 65%, the
value before frequent collection was started, to about 80%, and the percentage of
sperm with abnormal tails decreased from 30% to 15%. In experiment 2, the
percentages of HA and AR, and the ZP sperm count in specimens collected on day 5
were higher than those in specimens collected on day 1, and the differences in %
HA and in ZP sperm count were significant (P<0.05). The results demonstrated that
sperm motility, abnormality, and potential fertility in dogs with
asthenozoospermia and teratozoospermia can be temporarily improved by frequent
semen collection.
PMID- 9637296
TI - The location of a specific epitope in the SU proteins of palysis-inducing PVC
murine leukemia viruses.
AB - The location of a specific epitope in the SU proteins (gp70s) of PVC (PVC-111,
PVC-211, PVC-321 and PVC-441) murine leukemia viruses (MuLVs) among various MuLVs
was determined with chimeric viruses between PVC-211 and F-MuLV and a rat
monoclonal antibody to the gp70 of PVC-321. The epitope resided in the N-terminal
region from amino acid position 1 to 67 of SU protein and did not correlate to
the tropism against brain capillary endothelial cells of the F344 rat or Chinese
hamster ovary cells.
PMID- 9637297
TI - Urinary bladder rhabdomyosarcoma (sarcoma botryoides) in a young Newfoundland
dog.
AB - A 13-month-old female Newfoundland dog suffered from urinary bladder tumor.
Histologically the tumor consisted of round or fusiform cells, occasionally
having eosinophilic cytoplasms. Apparent mature rhabdomyoblasts possessing
elongated eosinophilic cytoplasm and cross striations were infrequently observed.
The tumor cells exhibited immuno-positive for anti-myoglobin, desmin and vimentin
antibodies. Ultrastructurally, tumor cells have abundant myofibrils in their
cytoplasm and Z bands were also detected. The present tumor was diagnosed as a
urinary bladder rhabdomyosarcoma in a Newfoundland dog, which has not been
frequently reported in dogs.
PMID- 9637298
TI - Histological variations of canine deciduoma induced in non pregnant horn at
different stages of unilateral pregnancy.
AB - Histological variations of canine deciduoma which was induced in the non pregnant
horn at several stages of unilateral pregnancy were examined. In the first half
of the unilateral pregnancy, deciduoma was characterized by the cystic glandular
hyperplasia corresponding to each of the stages in normal early placentation. In
the second half, deciduoma could not be induced and few histological reactions
were recognized. The endometrium looked normal for late diestrus with no growth
of the uterine glands. These differences might reflect the latent strength of the
uterine glands to proliferate and dilate in the stimulated periods.
PMID- 9637299
TI - Encephalitis in mice inoculated intranasally with an influenza virus strain
originated from a water bird.
AB - Five-week-old ddY mice were inoculated intranasally with a low virulent (4e) or
highly virulent (24a5b) avian influenza virus strain originated from a water
bird. None of mice in the 4e group showed clinical signs and brain lesions. Of
the 24a5b group, two mice died and one mouse was killed at a moribund state at
day 7 post-inoculation (PI). Four mice of the 24a5b group necropsied at day 5 or
7 PI had mild to severe encephalitis in the brain stem and the cerebellar white
matter. Influenza virus antigen was detected in neurons, glial cells and vascular
endothelium in the lesions. The distribution of the lesions seems to indicate the
transneuronal invasion of the virus via cranial nerve fibers into the brain.
PMID- 9637300
TI - Immunohistochemical study of protein kinase C in the testes of cattle and pigs.
AB - We investigated the expression of novel protein kinase C (PKC) delta and theta in
the testes of pigs and cattle using Western blot and immunohistochemical
analysis. PKC delta and theta are recognized in the testes of pigs and cattle by
Western blot analysis. We found in immunohistochemical study that PCK delta was
localized in the spermatids of seminiferous tubules, but not in the interstitial
cells, while PKC theta was recognized only in the interstitial cells of the
testes of in both species. These findings suggest that PKC delta and theta play
an important role in the development of spermatozoa and the regulation of
androgen in the testicular interstitial cells (probably Leydig cells),
respectively.
PMID- 9637301
TI - Application of hepatic tolerance tests to the functional reserve assessment in
rat models of fatty liver.
AB - The present study was designed to define whether maximal removal rate of
indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP)
response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and
plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional
reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2%
cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in
cholesterol and phospholipid values in serum during feeding periods differed
among the models, histopathologic examinations in the liver of almost all animals
revealed intermediate to severe fatty liver with or without fibrosis at each
termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed
choline-deficient or DL-ethionine diet, implying reductions in hepatic functional
mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose
showed no change in any of the models, suggesting that glucose metabolisms in the
models used may be preserved. These findings demonstrate that ICG Rmax and P/B
cAMP can apply to measurement of hepatic surviving reserve of fatty liver with
fibrosis.
PMID- 9637302
TI - Coproantigen detection in a survey of Echinococcus multilocularis infection among
red foxes, Vulpes vulpes schrencki, in Hokkaido, Japan.
AB - Detection of Echinococcus coproantigen using sandwich enzyme-linked immunosorbent
assay (sELISA) was performed on fecal samples of red foxes in Hokkaido, Japan.
Fecal samples were collected around fox dens in 1990 and 1992. The antibodies
used for sELISA recognize heat-resistant antigens, thus all fecal samples were
heated to render it safe for handling before examination. Detection of taeniid
egg in fox feces collected was considered as an indication of E. multilocularis
infection. In fecal samples collected in 1990 and 1992, coproantigen positive
results out of taeniid-egg positive cases were 38/40 (95.0%) and 95/97 (97.9%),
respectively. In addition, coproantigen was detected regardless of fecal
condition when collected from the field, suggesting that the antigens detected by
this method are quite stable. These results suggest that detection of
coproantigen is useful for field surveys of foxes naturally infected with E.
multilocularis.
PMID- 9637303
TI - Relationship between plasma testosterone concentrations and age, breeding season
and harem size in Misaki feral horses.
AB - Jugular vein blood samples were collected from 23 young and sexual mature feral
stallions to examine the relationship between plasma testosterone concentration
and age, breeding season or harem size. Testosterone concentration increased with
the age of the stallions until they formed their own harems, at about 4 to 6
years old. Seasonal variations in testosterone concentrations were observed, and
found to be significantly higher (P<0.001) throughout the breeding season than
non-breeding season, from 3 years of age. Testosterone levels were correlated
with harem size for individual stallions. It can be inferred from these results
that there is a relationship between plasma testosterone concentration and age,
breeding season and harem size.
PMID- 9637304
TI - The contrecoup injury in a cat case of traffic accident: MRI findings.
AB - The clinical application of MRI of a cat case of traffic accident was examined.
On admission, the animal was unconscious and remained so for 2 days. Radiographs
disclosed a fracture in the parietal bone. From the temporary unconscious status
and the fracture, cerebral damage was suspected and an MRI examination was
performed. The contrecoup injury in the cat case of traffic accident which could
not be diagnosed by radiography was diagnosed by MRI examination.
PMID- 9637305
TI - Cloning and mapping of the mouse Gpx2 gene encoding gastrointestinal glutathione
peroxidase.
AB - Gastrointestinal glutathione peroxidase (GSHPx-GI) is an enzyme expressed in
intestinal epithelial cells and may reduce hydroperoxides generated from the
ingested diet. We isolated a genomic clone containing the mouse Gpx2 gene
encoding 190 amino acids of GSHPx-GI. This gene is composed of two exons and an
intron. The nucleotide sequence of the coding region was 89.9% identical with
that of the human GPX2 gene. A TGA opal codon predicted to encode a
selenocysteine was identified at codon 40. A genomic clone containing a
pseudogene for the Gpx2 gene was also isolated. The nucleotide sequence of the
pseudogene was 98.3% identical with that of the mouse Gpx2 gene and showed
characteristics of a processed pseudogene. Linkage analysis using backcross mouse
progeny indicated the mouse Cpx2 gene and its pseudogene to be located on mouse
chromosomes 12 and 7, respectively.
PMID- 9637306
TI - Construction of recombinant vaccinia virus expressing Rinderpest Virus
nucleocapsid protein and its immunogenicity in mice.
AB - Recombinant vaccinia virus (rVV) was constructed by inserting Rinderpest Virus
(RPV) nucleocapsid (N) protein gene. The rVV expressed RPV-N protein in the rVV
infected cells. The rVV was shown to produce RPV-N-specific antibody in mice.
PMID- 9637307
TI - Effect of thromboxane synthetase inhibitor on feline infectious peritonitis in
cats.
AB - Two cats with abdominal effusion and anorexia were diagnosed as feline infectious
peritonitis (FIP). We tried to evaluate the effect of thromboxane (Tx) synthetase
inhibitor, ozagrel hydrochloride, on the progression of symptoms and
clinicopathologic data characteristic to FIP. After administration of Tx
synthetase inhibitor, improvement of appetite and activity, decreases of
peritoneal effusion, reduction of leukocyte number to normal level, and
improvement of hyper gamma-globulinemia were found in 2 cats with FIP. These
findings suggest that the vasculitis in FIP can be successfully treated with Tx
synthetase inhibitor which inhibits platelet aggregation.
PMID- 9637309
TI - Law, ethics and risk in nursing practice.
PMID- 9637308
TI - Comparative pharmacokinetic profiles of two norfloxacin formulations after oral
administration in rabbits.
AB - The pharmacokinetics and tissue distribution of two norfloxacin (NFLX)
formulations, norfloxacin-glycine acetate (NFLXGA) and norfloxacin nicotinate
(NFLXN), were compared after single oral administration with a dose of 5 mg
equivalent NFLX base/kg of body weight in twenty rabbits. The pharmacokinetic
characteristics of all formulations were fitted by a two-compartment open model.
The elimination half-life (T1/2beta) of NFLX (3.37+/-1.37 hr) was not significant
as compared with those of NFLXN (3.61+/-0.65 hr) and NFLXGA (3.93+/-1.54 hr). The
absolute bioavailability (F) of NFLX, NFLXN and NFLXGA was calculated as 29%, 45%
and 40%. In addition, tissue distribution of NFLXN and NFLXGA did not show any
differences of NFLX concentrations in liver, kidney, serum and muscle. From the
present results, it could be suggested that NFLXN and NFLXGA are considered to be
bioequivalent when they use oral medication for rabbits.
PMID- 9637310
TI - WHO tackles health risks in European prisons.
PMID- 9637311
TI - Role of nurses in the community care of schizophrenia.
PMID- 9637312
TI - Teenage risk from painkillers.
PMID- 9637313
TI - Towards a partnership in care: nurses' and doctors' interpretation of extremity
trauma radiology.
AB - Receiver operating characteristic (ROC) is a method of assessing the sensitivity
and specificity of a classification at a variety of thresholds. It allows a
quantitative comparison of several classifiers. It was used in this study to
compare doctors and nurses with respect to their ability to diagnose X-rays. X
ray interpretations were measured using a confidence rating scale, on 50
radiographs from a generated library of extremity X-rays following trauma. The
catalogue of radiographs were selected from real cases of extremity trauma which
were considered representative of typical accident and emergency case scenarios.
The interpretations of doctors and nurse practitioners were compared with the
gold standard of the consultant radiologist. No significant differences were seen
between the two groups. This study is based on work done for a master's thesis by
one of the authors (Overton) supervised by the other author.
PMID- 9637314
TI - Handling and control of peripheral intravenous lines.
AB - The purpose of the study was to describe nurses' routines in connection with the
planning, care and handling, and documentation of a peripheral intravenous
cannula (PIV) and also to examine factors that control how nurses act. Nurses and
physicians in three English hospitals were interviewed. The results showed a
difference between nurses' and physicians' opinions about PIV routines, except in
few cases. The PIV was inserted by the physicians while the nurses took care of
and documented its care and handling. In many cases the insertion of the PIV was
also documented by the nurses. Although small PIVs and short insertion time had
previously been recommended, many physicians preferred large cannulae and an
insertion time of between 3 and 7 days. All nurses and six physicians had the
opinion that the cannula should be changed more often, but this did not happen.
Some physicians maintained that the nurses' care and handling varied. On the
other hand some criticism had been expressed by the nurses about unclear
directives from the physicians. English participants were aware that
unsatisfactory routines existed and that the policy had not always been followed.
PMID- 9637315
TI - 'Out of the sighs'--an existential-phenomenological method of clinical
supervision: the contribution to palliative care.
AB - This paper describes a method of clinical supervision that engages a Macmillan
home care nurse in an existential-phenomenological exchange. A synthesis of
Egan's method of problem management and phenomenological interviewing, is offered
as an approach to clinical supervision considered appropriate for palliative care
nursing. Through a case study approach the author affords glimpses into the life
world of palliative care nursing. It is suggested that conflicts experienced in
the field both manifest themselves in the supervisory encounter and parallel the
nurse's and supervisor's own existential struggles. The discussion as such throws
light on what is, frequently, the heart rending nature of palliative care nurses'
chosen area of work and illuminates the mutual profundity of the experience of
palliative care.
PMID- 9637316
TI - Patients' and nurses' perceptions of the quality of nursing care in Kuwait.
AB - Using an exploratory research method and a purposive sample of 259 subjects (109
of whom were nurses and 148 patients), data were collected using an instrument
consisting of the elements of the nursing process. Four hypotheses were tested,
using the analysis of covariance and the t-test The result of hypothesis I showed
that there was no statistically significant difference in the perception of the
quality of nursing care between the patients in the medical and surgical units of
the five study hospitals. Hypothesis 2 indicated that there was no significant
difference between nurses in the medical-surgical units in the areas of
assessment, planning and implementation. However, a significant difference was
found for accountability and responsibility. Further analysis using a t-test
showed a significant difference between nurses in the medical and surgical units
in the areas of accountability and responsibility. The data for hypothesis 3 and
4 yielded no significant difference in the perceptions of quality care by nurses
according to work experience and by patients in all hospitals regardless of the
patients' age and sex.
PMID- 9637317
TI - A review of the outcome of stoma surgery on spinal cord injured patients.
AB - A study was conducted to determine the short-term and long-term outcome of stoma
formation on spinal cord injured (SCI) patients. Twenty-seven medical records of
SCI patients with colostomy, ileostomy or urostomy were reviewed. Eighteen SCI
patients were then interviewed or completed a comprehensive questionnaire to
determine the physical and psychological effects of the surgery and to assess
changes in lifestyle due to the formation of the stoma. It was found that bowel
and bladder management was greatly improved in most cases, resulting in improved
quality of life for these patients. Other positive psychological effects were
noted and the question of a colostomy being offered earlier in the rehabilitation
of the SCI patient was raised.
PMID- 9637318
TI - Nurse caring behaviours.
AB - The purpose of this research paper is to examine caring behaviours and how they
relate to nurses practice from the psychiatric and general nurses' views. Whether
this caring is influenced by the nurses' age, gender or qualification is also
examined. The convenience sample used were nurses (n = 118) of all grades and
experience in a general hospital and in a psychiatric hospital. The Care-Q
instrument was used. The response rate was 66%. Statistical analysis included
rankings of sub-scale and individual items and the chi-square test of
association. The results show that nurses ranked physically based caring
behaviours higher than affective behaviours. They emphasized monitoring and
comforting behaviours but paid less attention to anticipatory behaviours. Gender
appeared to have the greatest influence on what caring behaviours were valued.
Male nurses were less likely than female nurses to be accessible, forming
trusting relationships or performing comforting behaviours. The results challenge
both nurses and nurse educators to examine caring behaviours in nursing practice.
PMID- 9637319
TI - Case management: a review of the definitions and practices.
AB - Case management has been suggested as an innovative strategy which facilitates
the linking of quality and cost-effective care. However, there is little
consensus about what is actually being introduced under the name of case
management. It is suggested that this absence of a clear understanding of case
management has been an obstacle in moving forward case management practice and
research. This paper presents a critical review of the confusion surrounding case
management with an attempt to unravel issues relevant to the implementation of
case management into community nursing practice in Hong Kong. It is concluded
that there is a need for different definitions of case management as a result of
the differences in the cultural and health care context in which it is being
practised. Also, if case management programmes are to be advanced, there needs to
be more co-ordinated effort in researching not only the expected outcomes but
also the structures and processes of these programmes so that findings of similar
case management programmes can be compared for ways of future improvement.
PMID- 9637320
TI - Privacy in hospital.
AB - Privacy during hospitalization can be jeopardized as caring situations are often
intimate. The aims of the current study were to explore patients' and nurses'
attitudes towards privacy and to study whether nurses' perceptions of patients'
privacy needs corresponded with the patients' own reported needs. Two
questionnaires were used for the data collection, which included 120 consecutive
patients and 42 nurses responsible for the participating patients' individual
care. The main findings indicated that patients and nurses agree in the ratings
of the major components of privacy in general, but privacy in hospital was
estimated more highly by the nurses than by the patients themselves. Being
allowed to talk to the physician in private was given the highest preference.
Patients in long-term care had higher privacy preferences than those in acute
care. An explanatory approach is needed to study the need for privacy in
different caring situations and how privacy needs could be recognized and met by
nurses.
PMID- 9637321
TI - The philosophical and sociological context of mental health care legislation.
AB - This paper explores mental health legislation from a philosophical and
sociological perspective. It is argued that mental health law exists primarily as
a coercive social control instrument and that the maintenance of a separate
legislative framework for the mentally ill is based upon dubious legal and
philosophical grounds. The need for changes in mental health law has been
accelerated by the move in Britain toward care in the community. One of the most
important issues at the centre of the debate revolves around the concept of
'dangerousness' and mental disorder. The research into the extent to which the
risk of violence can be predicted appears problematic from a reform perspective.
Prediction is considered to be the overriding problem that leads to a violation
of patients' civil rights, especially in relation to black and ethnic minority
groups. Equity in law is necessary for the protection of patient's rights and
particularly for the protection of those people who enter mental health care
systems concerned with issues of control at the expense of care.
PMID- 9637322
TI - Perceived social support and community adaptation in schizophrenia.
AB - Prompted by the continuing transition to community care, mental health nurses are
considering the role of social support in community adaptation. This article
demonstrates the importance of distinguishing between kinds of social support and
presents findings from the first round data of a longitudinal study of community
adaptation in 156 people with schizophrenia conducted in Brisbane, Australia. All
clients were interviewed using the relevant subscales of the Diagnostic Interview
Schedule to confirm a primary diagnosis of schizophrenia. The study set out to
investigate the relationship between community adaptation and social support.
Community adaptation was measured with the Brief Psychiatric Rating Scale (BPRS),
the Life Skills Profile (LSP) and measures of dissatisfaction with life and
problems in daily living developed by the authors. Social support was measured
with the Arizona Social Support Interview Schedule (ASSIS). The BPRS and ASSIS
were incorporated into a client interview conducted by trained interviewers. The
LSP was completed on each client by an informal carer (parent, relative or
friend) or a professional carer (case manager or other health professional)
nominated by the client. Hierarchical regression analysis was used to examine the
relationship between community adaptation and four sets of social support
variables. Given the order in which variables were entered in regression
equations, a set of perceived social support variables was found to account for
the largest unique variance of four measures of community adaptation in 96 people
with schizophrenia for whom complete data are available from the first round of
the three-wave longitudinal study. A set of the subjective experiences of the
clients accounted for the largest unique variance in measures of symptomatology,
life skills, dissatisfaction with life, and problems in daily living. Sets of
community support, household support and functional variables accounted for less
variance. Implications for mental health nursing practice are considered.
PMID- 9637323
TI - Psychosocial changes following retirement.
AB - This study was designed to: (a) identify the perceptions of retirees about
changes in their life patterns during retirement; (b) investigate the kinds of
adjustment problems occurring in retirement as a basis for developing prevention
oriented pre-retirement programs; and (c) identify extant factors which could
demonstrate underlying themes relating to retirement adjustment. A 72-item,
multiple response questionnaire was used to gather demographic data, information
on use of time, pre-retirement planning, health problems, changing life patterns,
and adjustment to retirement. It is the latter which is reported in these
findings. The population included 1565 retirees from a designated company living
in the south-eastern United States of America, with a response of 764 subjects
(48.82%). Findings suggest the respondents were generally healthy and well
adjusted; however, numerous adjustment problem areas were identified within the
six life patterns. Additional factor analysis (principal components) demonstrated
four factors of particular importance: satisfaction with retirement, retirement
concerns, spousal relationships, and pre-retirement preparation outcomes.
PMID- 9637324
TI - Mentally restorative experiences supporting rehabilitation of high functioning
elders recovering from hip surgery.
AB - Because mentally restorative experiences are pivotal in the context of
rehabilitation and recovery, a prospective descriptive study was designed to
learn more about the opportunities for, locations, and actions taken by, a group
of elderly people (n = 8) over the age of 60 (average age = 82.5) that resulted
in agreeable or pleasurable states of mind and perceived improvement in their
ability to pay attention. Both structured and unstructured interviews were used
to describe elderly patients' past and current patterns of and preferences for
mentally restorative experiences. Data collection procedures were utilized during
complete lengths of stay (range = 14-62 days) in sub-acute care. Results
demonstrate that the actions elderly people take to create opportunities for
mentally restorative experiences are related to past patterns of restorative
activities, opportunities made available by the facility, special circumstances
of their care, environmental limitations in the immediate care environment, and
the degree to which external factors (such as family visits) are readily
available. Implications for designing and managing the care environment are
discussed.
PMID- 9637325
TI - Labour ward midwives' perceptions of stress.
AB - This exploratory study set out to examine labour ward midwives' perceptions of
stress. It utilized a combination of two self-report questionnaires, one devised
by McGrath et al. and the GHQ12. Additional qualitative data were collected by
asking midwives to produce narratives about recent stressful events. A
convenience sample of the 43 midwives formed the study population and a response
rate of 77% was achieved. Quantitative data were analysed using descriptive
statistics and qualitative narratives were explored for content analysis.
Midwives in this study demonstrated their awareness of stress in their working
and personal lives and many took active steps to redress the negative effects
with exercise, hobbies and talking with colleagues. However, the study revealed
that 78% of the midwives indicated that having insufficient time to perform their
duties was very stressful, paralleled by their perceived inability to influence
work-based decisions. The study revealed that both medical and midwifery
colleagues frustrated their endeavours to change an unsatisfactory condition. The
GHQ12 revealed 30% of the midwives had scores above the threshold level of 2
indicating psychiatric morbidity and this is of major concern. The narratives
revealed that lack of communication between the professionals about decision
making was a major source of stress and as a result of this study efforts to
improve multidisciplinary communication through the development of journal clubs
and planned social activities is under consideration by the unit. Overall, the
findings from this study highlight stress as a potential, occupational health
problem in the working lives of some labour ward midwives.
PMID- 9637326
TI - Infertility and early parent-infant interactions.
AB - Approximately 50% of infertile couples will become parents through pregnancy or
adoption, but they experience major difficulties while working towards this goal.
Infertility treatments are associated with physical pain and psychological
distress, and adoption procedures are prolonged and emotionally stressful. The
extent to which these stressors alter the parenting of these couples is not
known. The purpose of this study, therefore, was to examine the early parent
infant interactions in infertile couples who become parents through pregnancy or
adoption. Two groups of infertile couples (30 who achieved pregnancy and 21 who
adopted) and a group of 19 couples without fertility problems were observed
interacting with their infants twice, 7 to 21 days after the infant's arrival and
a week later, at a time when both parents were at home. Their babies were between
9 days and 5 months of age. Behaviours of the mother, father and infant were
recorded every 10 seconds, beginning when the baby was picked up and ending when
the baby was put down asleep or 1 1/2 hours had passed. Repeated measures ANOVAs
were used to compare the three groups over the observations. There were no
differences between fertile and infertile biological parents. Adopted infants
showed more alertness, less sleeping, more smiles, and more looking than
biological infants. Adoptive mothers spent less time as the sole interactor.
Adoptive parents spent more time in playing with their infants and held and
touched them less than did biological parents. Infertility, therefore, does not
appear to affect early parenting. In general, the amounts of behaviours exhibited
by infertile biological parents were very close to those of fertile parents.
Differences in the behaviours of adoptive as compared to biological parents can
best be explained as responses to the behaviours of their older infants, rather
than as evidence of different parenting styles.
PMID- 9637327
TI - The role of cognitive-behavioural therapy in the management of pain in patients
with sickle cell disease.
AB - Painful crisis is the most common manifestation of sickle cell disease and
accounts for the second greatest number of admissions with an average length of
stay of 7 days in central London. Despite this frequency of admissions, the
management of pain is fraught with problems. This is not surprising since the
psychological challenges presented by sickle cell disease are manifold, resulting
in significant psychological distress for some individuals. This paper considers
the literature on the psychosocial impact of sickle cell disease, and the
American research evidence which suggests that pain management strategies that
incorporate a psychological intervention can significantly reduce psychological
distress as well as hospital admissions. Britain has been slow to incorporate
psychology in the pain management strategies, and we have embarked on research to
fill this gap. Although this research constitutes work in progress, an argument
is put forward for utilizing the cognitive-behavioural perspective in the
management of pain in sickle cell disease and we conclude by giving a brief
summary of pilot work which is both the foundation and justification for the
current ongoing research.
PMID- 9637328
TI - Towards a politics of trust.
AB - This paper draws upon sociological theory to demonstrate that the manufacture and
deployment of trust is an integral part of the function of complex systems such
as health care. The discussion begins by identifying the error within the nursing
literature which arises from a rather technical conceptualization of trust. This
tends to limit the dimensions to trust which is established, and fails to
recognize that trust may be subject to competition and conflict. The paper
continues by drawing upon the work of two theorists, Niklas Luhmann and Susan P.
Shapiro, to demonstrate how trust functions within systems such as health care
and the mechanisms through which it is controlled. The title of this paper,
'Towards a politics of trust', identifies that this is merely the first stage in
the analysis. Further stages are necessary which analyse the ways in which power
is exercised in the conflict for control within discrete elements of the system.
PMID- 9637329
TI - A framework to identify learning needs for continuing nurse education using
information technology.
AB - This paper concerns one of the main problems facing continuing nurse education,
that of matching the learning needs of the individual nurse with the needs of the
care setting. This endeavour is inescapable because of the necessity for giving
high quality care within financial restraint. Modern information technology, it
is suggested, can be helpful in fulfilling the task more easily. A theoretical
framework is introduced as a possible solution for developing a computer program
which, it is the hope of the author, will be available in the not so far future.
PMID- 9637330
TI - 'The buck stops here': accepting responsibility for learning and actions after
graduation from a problem-based learning nursing education curriculum.
AB - Despite the increased attention that problem-based learning has received as an
appropriate pedagogical technique for educating adults for professional practice,
reports that evaluate the process are rare and usually relate to professions
other than nursing. A study was undertaken in order to discover the graduates'
own perceptions of a problem-based learning programme and its effectiveness in
preparing them for the reality of their chosen profession. Twelve practising
graduate nurses who had completed the programme were interviewed according to the
ethnographic method. Three categories were identified from the data: 'and all of
a sudden...', which describes the transition from PBL student to staff nurse;
'not an unthinking assistant', where the characteristics that the PBL graduates
believe make them different from traditionally trained nurses are described; and
'the buck stops here', which describes the sense of personal responsibility that
the graduates experience in terms of their learning and actions.
PMID- 9637331
TI - Learning by reflection: the effect on educational outcomes.
AB - Learning by experience involves being able to reflect on a personal happening and
through a process of analysis, come to understand it. Such an activity should
result in 'deep learning' when carried out in a structured way. Higher education
establishments are keen to develop such learning methods in students, as a
secondary effect of this form of learning is to create student independence from
the teacher. This is a much sought after ability as recent government changes
have meant higher student numbers without a corresponding rise in teacher
numbers. This threatens the quality of student knowledge unless it is compensated
for in some way. This study sets out to examine the learning of two student
groups. The experimental design was that of group comparison using matched pairs
of students. One group, the experimental group, were exposed to reflective
teaching methods, whilst the other group (the control group) were exposed to
conventional teaching methods only. At the end of a set period of time, the
learning achieved in both groups was estimated using an especially designed test
paper. The results obtained from both groups were compared and it was found that
there was no significant difference obtained in the learning between the groups
(P>5%) Therefore, we concluded that students learnt just as well using reflective
methods when compared to the conventional methods of learning. However, the
potential for enhancement of learning was evident and invites further
investigation. All the students in this study were on the Diploma in Higher
Education (Nursing) course. The subject area used throughout the study was in the
biological sciences.
PMID- 9637332
TI - Planning flexible learning to match the needs of consumers: a national survey.
AB - The injection of market forces into the National Health Service (NHS) has led to
nurse education being viewed as a commodity which educational institutions supply
and NHS employers purchase. Conscious of the costs of paying for courses within
this new consumer culture, NHS trusts and other health service employers are
increasingly looking for cost-effective flexible training to educate their
workforce quickly and efficiently. Parallel to this is the accelerated demand for
continuing professional development (CPD) brought about by the inception of the
UKCC's Post-Registration Education and Practice Project (PREPP). Both registered
and enrolled nurses are finding they need professional updating and skills and
thus increased access to courses. The increased demand for education and training
brought about by these changes cannot be met through traditional methods alone,
requiring educational institutions to re-appraise their methods of delivery and
introduce more flexible approaches to learning. There is every evidence that this
is now the case with open learning, distance learning and flexible approaches to
learning ever growing in popularity as providers of nurse education recognize the
benefits such approaches offer. The emphasis is on meeting the diverse needs of
the health care employers and individuals by providing education that is
flexible, learner-centred and customer focused. This paper presents the findings
of a national survey to ascertain how providers of flexible education plan
educational programmes to meet the needs of their customers. Based on data
collected from 120 educational institutions within the higher education, health
and social care and private sectors, it highlights: the ways in which flexible
learning programmes and courses are delivered; what aspects of flexibility are
considered important when designing programmes to meet the needs of prospective
customers; and what approaches are used to assess demand for flexible education.
The study stresses the need for providers of flexible education to take into
account the dual perspectives of those who have a stake in the flexibility of
nurse education; NHS employers as funders of students and individual healthcare
professionals themselves.
PMID- 9637333
TI - The role of reflection in single and double loop learning.
AB - A recent review of the literature on reflective practice in nursing indicates
that approaches to its promotion in the United Kingdom and Australia appear to
differ. In the United Kingdom, these approaches promote single-loop learning
whereas in Australia the approaches adopted attempt to promote double-loop
learning. In this paper single and double-loop learning will be defined and the
limitations of single-loop learning in nurse education will be discussed. In
addition, definitions of reflective practice, the purposes it is claimed to serve
and a range of frameworks developed to promote its development will be reviewed.
Inconsistencies between espoused purposes and suggested frameworks will be
discussed. The paper will also include a description of recent initiatives
implemented in Western Sydney, Australia, to foster nurses' double-loop learning.
PMID- 9637334
TI - Reflection and patterns of knowing in nursing.
AB - Over the last decade nursing has progressed from a reliance on empirical theory
applied to practice to a recognition that experience develops knowledge that can
guide the actions of practitioners. Reflection is a means of surfacing
experiential knowledge, and students may begin to use reflection as their
experience of nursing accumulates. As Carper was a key figure in widening that
knowledge accepted as knowing in nursing beyond the empirical, it is both
justified and recommended that her work should be incorporated into reflective
practice. Johns has integrated Carper's work in his model of guided reflection
and this paper briefly examines this combination. The main focus is on two
further patterns of knowing: unknowing and sociopolitical knowing. These patterns
are examined and the contribution they could make to reflective practice is
discussed.
PMID- 9637335
TI - Using bioscience knowledge in nursing: actions, interactions and reactions.
AB - This paper draws on empirical data from a study undertaken to explore the
outcomes of the applied physiology component of a post-registration diploma in
nursing (DN). Most students completing the DN were utilizing their new bioscience
knowledge in clinical practice, and reported increased participation in
interprofessional discussions and team decisions. Respondents found themselves
better able to monitor and evaluate doctors' decisions and this led to friction
with some medical colleagues. However, the strongest resistance came from senior
nurses, very few of whom had completed advanced nursing courses in bioscience and
who were generally unwilling to allow respondents to develop new roles. General
managers were also perceived as a major barrier to change. There is little
evidence of tangible benefits to the nurses themselves: most saw the DN
qualification as a way of protecting their status as professional nurses in the
face of managerially driven organizational change, rather than as a route to
occupational advancement.
PMID- 9637336
TI - 'A good person does not feel envy': envy in a nursing community.
AB - The definition of envy is commonly based on psychoanalytical views of
organizational culture. The purpose of this paper is to describe envy in a
nursing community. The population study consisted of random sample of 120
subjects drawn from among the employees of one central hospital in Finland. The
study material consisted of data collected by questionnaires (response rate 65%).
The data were processed by various statistical methods. Open-ended questions were
analysed by inductive content analysis. The results of this study indicated that
the employee's view of his/her official position in the nursing community,
his/her relationships with his/her fellow workers and the management as well as
relationships with other nursing communities are all related to envy. The
employee's view of his/her official position intensified his/her feelings of
envy, if he/she had other negative feelings, anxiety, dissatisfaction with
him/herself, and negative feelings towards fellow workers. The major object of
envy was fellow workers' salaries. Envy towards other nursing communities was
generated by alleged differences in the amount of labour, or by the charge
nurse's greater interest in other sections. Employees coped with envy by hiding
these feelings and being modest. Women coped with envy by being silent, while men
denied the value of the object of envy.
PMID- 9637337
TI - The effects of aftercare on chronic patients and frail elderly patients when
discharged from hospital: a systematic review.
AB - The purpose of this systematic review was an assessment of the efficacy of
aftercare in chronic patients and the frail elderly when discharged from
hospital, as regards quality of life, compliance, costs, medical consumption and
quality of care. In pursuit of this goal, 17 publications on the effects of
aftercare after discharge from hospital were examined. A systematic assessment of
methodological quality by two blinded independent reviewers resulted in a
consensus score (0-100 points), based on four categories: the study population,
description of the interventions, measurement of the outcome and the analysis and
presentation of the data. Only three of the 17 studies scored more than 50
points, indicating that most of the studies were of poor methodological quality.
The most prevalent methodological problems were that co-interventions were not
avoided, a placebo group was lacking, the assessment was not blinded and the
analysis was not made on the basis of the intention-to-treat principle. The
majority of the studies did not report clear beneficial effects in favour of the
intervention group. The positive effects reported were limited to costs and
quality of care.
PMID- 9637338
TI - A case study analysis of nurses' roles, education and training needs associated
with patient-focused care.
AB - A case study analysis of a trust hospital piloting patient-focused care (PFC) on
two wards was undertaken with a view to determining the education and training
needs of registered nurses. The impact of PFC on the roles of the nurses was
examined and nurses' perceptions of their training needs, and the extent to which
these have been met was explored. The competency model which has been
operationalized to meet the training needs was also determined. Twenty-three
members of staff were interviewed including members of the project team, care
leaders (registered nurses), managers and trainers, and various documents were
examined. Multi-skilling of staff has so far been limited to nurses. The cross
training programme developed, which is far from complete, is based on a model of
competence which focuses on specific task skills. It is suggested that an
'output' model of competence which focuses on the whole work role may be more
appropriate for qualified nurses vested with the co-ordination of care in
accordance with multi-disciplinary protocols. In addition, given that a whole
range of 'soft skills' are needed to manage the changing role boundaries,
Spencer's model of competency is also an appropriate model to adopt for the
identification of superior performance from both care leaders and clinical
managers. Implications for both pre- and post-registration education and training
are highlighted. Inadequate resourcing is currently a major weakness which could
jeopardize the entire project which otherwise is viewed very favourably by the
majority of those who participated in this study.
PMID- 9637339
TI - Down-regulation of tumor necrosis factor-alpha, moderate reduction of interleukin
1beta, but not interleukin-6 or interleukin-10, by glucan immunomodulators
curdlan sulfate and lentinan.
AB - The effects of glucan-based immunomodulators curdlan sulfate (CRDS) and lentinan
on cytokine production stimulated by lipopolysaccharide (LPS) in bacillus
Calmette-Guerin (BCG)-primed mice were investigated. Pretreatment with CRDS or
lentinan before LPS administration induced a striking inhibition of up to 89% of
circulating tumor necrosis factor-alpha (TNF), a moderate reduction of 25% of
interleukin (IL)-1beta, no significant differences in IL-6 or IL-10 levels, and a
marked depression of chemiluminescence activity. Animals receiving CRDS prior to
infection with alpha-hemolysin positive Escherichia coli inhibited measurable TNF
production by 63%. The ability of CRDS and lentinan to significantly reduce the
TNF production in vivo indicates the potential of glucans in possible therapeutic
strategies that are based on down-regulation of TNF.
PMID- 9637340
TI - Polygenic control of the expression of biological activities of an antitumor
polysaccharide, lentinan.
AB - Genetic studies were carried out on two in vivo responses of lentinan, delayed
type-acute phase responses (DT-APR) and vascular dilation and hemorrhage (VDH).
Linkage analyses showed that DT-APR was controlled by two recessive genes, ltnr1
and ltnr2, which were mapped on chromosome 3 and 11, respectively. VDH was also
found to be controlled by polygenes. One dominant major gene, Ltnr3, and three
dominant minor genes, Ltnr4, Ltnr5, and Ltnr6, were mapped on chromosomes 6, 9,
15 and 16, respectively.
PMID- 9637341
TI - The use of recombinant adeno-associated viral vectors for the transduction of
epithelial tumor cells.
AB - Using hight-titer recombinant adeno-associated viral vectors (rAAV), we have
investigated the feasibility of cancer vaccines from tumor explants. In a first
set of experiments, rAAV vectors expressing firefly luciferase reporter genes
were used to transduce different human tumor cell lines. At day three post
transduction, all of the human tumor cell lines tested showed high levels of
luciferase expression. To further evaluate rAAV-mediated gene transfer efficiency
into primary tumor cells, we transduced freshly isolated tumor cells from
malignant melanoma and ovarian carcinoma patients. As a remarkable result,
reporter gene expression in primary tumor cells was significantly higher than in
the tested established tumor cell lines. These data could also be reproduced with
a rAAV/lacZ vector, since the portion of successfully transduced primary tumor
was higher than 90%. Taken together, our data demonstrate that rAAV-mediated gene
transfer is a very efficient method for the transduction of freshly isolated
human tumor cells and may allow the generation of potent autologous cancer
vaccines.
PMID- 9637342
TI - Biomarkers for predicting response to regional chemo-immunotherapy in liver
metastases from colorectal carcinoma.
AB - Differences in therapeutic outcomes after regional chemotherapy or chemo
immunotherapy in liver metastases from colorectal carcinoma cannot be explained
only by variations in the regimens of treatment. This study was undertaken to
assess the potential of several tumor-associated markers of biological behavior
(biomarkers) to predict therapeutic response in order to pre-select the best
candidates for this demanding treatment. In a group of 21 patients, flow
cytometric DNA ploidy provided the most accurate prediction, with a response rate
of 88% in 8 DNA diploid tumors compared to 31% in 13 DNA aneuploid cases (P =
0.017) and a difference in overall survival of nine months (20.4 vs 11.3, P =
0.041). Only a slight trend towards improved response rate was observed when we
immunohistochemically detected p53 anti-oncoprotein expression in 11 (52%) p53
positive tumors (P = 0.063). Other immunohistochemical biomarkers as P
glycoprotein (p170), p21/WAF, mdm2, c-erbB-2, and proliferative activity of tumor
(detected either by anti-PCNA and anti-Ki67 monoclonal antibodies or as a flow
cytometric proliferation index) were unrelated to the outcome of treatment. DNA
ploidy and expression of p53 protein are potential biomarkers for predicting the
response to regional chemotherapy of liver metastases from colorectal carcinoma.
PMID- 9637343
TI - Clinical study of the effect of the preparation DEODAN on leukopenia, induced by
cytostatics.
AB - The aim of the study is to establish the effect of the preparation DEODAN on
leukopenia induced by chemotherapeutics in oncological patients. DEODAN is an
oral preparation, obtained from lyzozyme lysates of Lactobacillus bulgaricus
strain "I. Bogdanov patent strain tumoronecroticance B-51" ATCC 21815, called
shortly LB51. In the study there are included two groups of patients--from
National Oncological Centre, Sofia, the other from Clinic of Medicine, Bertha
Academic Hospital, Clinics of Duisburg, Duisburg. All the patients, (78) have
undergone combined chemotherapy. In all patients, leukopenia has been established
in moderate and medium levels. The scheme of the application of DEODAN has been 3
g, three times a day before meals, from the first day of establishing the
disturbances of the haemopoesis. The treatment lasted until the restoration of
the haematological values. Only DEODAN was applied. The results obtained show
that the recovery of the WBC count (values above 3000) took place in all of the
patients between days 3 and 5. None of the patients displayed any infectious or
febrile complications, as a result of the applied chemotherapy and the treatment
with the preparation. DEODAN also improves the general condition of the patients.
PMID- 9637344
TI - Preclinical studies with prothymosin alpha1 on mononuclear cells from tumor
patients.
AB - The immunomodulating potential of the thymic protein prothymosin alpha1 (Pro
alpha1) on the lymphocyte and monocyte directed antitumor reactions of melanoma
and colorectal tumor patients in comparison with healthy controls were studied in
vitro. On average, tumor patients showed lower NK- and LAK-cell activities than
healthy controls, being associated with a lower adhesion capacity to tumor target
cells. The NK-cell activity of the tumor patients was inversely related to the
tumor stage. Pro alpha1 stimulated the impaired patients LAK-cell activity only
at an early stage of disease. The Pro alpha1 effects were associated with an
increased adhesion of lymphocytes to tumor target cells and an increased
secretion of deficient IFN-gamma and IL-2 secretion. By flow cytometry, Pro
alpha1 in combination with IL-2 increased the NK-cell marker CD56, CD16/56 and
CD25 as well as CD18/11a adhesion molecule expression. Monocytes from tumor
patients showed deranged tumoristatic activities compared with healthy controls.
Pro alpha1 elevated the mean of the antitumor activity, when applied alone or in
combination with rIFN-gamma. In the presence of IFN-gamma, Pro alpha1 stimulated
the adhesion of monocytes to cultured tumor cells, mainly by increasing CD54
expression. Pro alpha1 stimulated alone or in combination with IFN-gamma the TNF
alpha and IL-1beta secretion by monocytes and decreased the high PGE2 and TGF
beta level, especially in the patients groups. Perspectively, this may provide
the basis for applying Pro alpha1 in selected antitumor immunotherapy protocols.
PMID- 9637345
TI - Natural and synthetic thymic peptides as therapeutics for immune dysfunction.
AB - Natural thymic peptides have been isolated from calf thymus by mild acid
extraction. Pharmaceutical containing natural peptides (Thymalin) was put into
practice as immunocorrector. One of the immunomodulatory molecules (L-Glu-L-Trp)
has been isolated from Thymalin by reversed-phase high performance liquid
chromatography. Pharmaceutical containing this agent (Thymogen) was designed on
the base of synthesized dipeptide. A novel immunomodulatory dipeptide was
synthesized and termed Vilon. Both natural and synthetic pharmaceuticals
activated T-cell differentiation, T-cell recognition of peptide-MHC complexes,
induced the changes in intracellular composition of cyclic nucleotides and
cytokine [interleukin (IL-2), interferon (IFN)] excretion of blood lymphocytes.
Synthetic dipeptides activated neutrophil chemotaxis and phagocytosis. They had
no influence on antioxidant response in thymocytes in comparison with natural
peptides. Thymalin and Thymogen were used in persons with chronic pathology and
immune dysfunction. The results indicate that thymic peptides participate in the
regulating mechanisms of inflammatory processes as cytokine antagonists and show
the difference between natural and synthetic products. It is important for the
drugs designed to prevent immune dysfunction development.
PMID- 9637346
TI - Morphological and pharmacological evidence for the existence of brain regulatory
circuits in the immune response.
AB - Muramyl dipeptide (MDP) has a variety of biological effects including the effect
on CNS, such a promotion of sleep, fever, analgesic effect or some behavioural
changes and of course a very potent effect on immune system. The latter effect is
at least partly mediated through the structure in CNS. With the small
electrolytic lesions which were placed in brain from the spinal cord through the
brain stem up to the cerebral cortex we have identified a number of structures
such as medial frontal cortex (area Cg1-Cg3), subnucleus basomedialis and
centralis of amygdala, subnucleus medialis and dorsolateralis of nucleus
parabrachialis, lateral part of reticular formation (monoaminergic groups A1-7)
and the part of the reticular formation (serotonergic groups B6-B8) which are
evidently involved in the immunomodulatory and immunoadjuvant effect of muramyl
dipeptide. The results of experiments also suggest that the interaction between
neuroendocrine and immune systems might take place on the level of some of above
mentioned anatomical structures.
PMID- 9637347
TI - Modulation of neutrophil apoptosis by psychological stress and glucocorticoid.
AB - Neutrophils play a pivotal role in host defense against bacterial infection,
however, these cells may have a harmful effect on normal tissues under certain
pathological conditions. We demonstrate here that apoptosis of these cells is
modulated by psychophysical stress and its related hormones, suggesting that
psychoneural systems may exert an effect on host defense through modulating
neutrophil survival.
PMID- 9637348
TI - Airway hyperresponsiveness: first eosinophils and then neuropeptides.
AB - Airway hyperreactivity to bronchoconstrictor mediators is a main characteristic
in the majority of asthmatic patients and correlates well with the severity of
the disease. The airways of asthmatic patients are characterized by an
inflammatory state resulting in activation of lung tissue cells and attraction
and infiltration of leukocytes from the blood. The accumulation of eosinophilic
leukocytes is a prominent feature of inflammatory reactions that occurs in
allergic asthma. The increase in number of eosinophils is important since it
correlates in time with an increase in bronchial hyperresponsiveness. Viral
respiratory infections can also induce eosinophilia and airway
hyperresponsiveness in humans and animals and can worsen asthmatic reactions.
This report reviews current opinions on the relationship between inflammation
induced eosinophil accumulation/activation and the development of airway
hyperresponsiveness and the possible role for sensory neuropeptides in this
process. Firstly, CC chemokines play an important role in allergic airway
inflammation and respiratory viral infections leading to eosinophil recruitment.
Secondly, it can be concluded that IL5 is involved in the development in airway
hyperresponsiveness. IL5 has profound effects on eosinophils as promoter of
growth, differentiation and proliferation, chemoattractant, activator and primer.
However, it is conceivable that in animal models for allergic asthma besides IL5
other regulatory mediators may be involved in eosinophil migration and activation
in the lung, which in turn will lead to airway hyperresponsiveness. Recent data
support the possible role of eotaxin and its eosinophil-specific receptor CCR-3
in eosinophil chemotaxis and activation in allergic asthma. Moreover, it is
suggested that the development of airway eosinophilia in vivo involves a two-step
mechanism, elicited by eotaxin and IL5. The precise mechanism by which
eosinophils induce bronchial hyperresponsiveness is at present unknown. Sensory
neuropeptides could be important mediators in this process, since it has been
demonstrated that airway nerves are surrounded by and infiltrated with
eosinophils after antigen challenge. Sensory neuropeptides could be the final,
more downstream, common pathway after eosinophil infiltration and activation in
inducing airway hyperresponsiveness due to allergen inhalation or respiratory
viral infections. In conclusion, in the process of the development of airway
hyperresponsiveness observed during viral infections or in allergic asthma, the
IL5/eotaxin-induced infiltration and activation of eosinophils in the airways is
evident. Following this step, eosinophil-derived inflammatory mediators will
induce the release of sensory neuropeptides (possibly NK2-receptor activating
tachykinins) which in turn will lead to airway hyperresponsiveness.
PMID- 9637349
TI - Neuropeptides in the immunomodulation: substance P-induced stimulation of immune
response in mice.
AB - The effects of substance P (SP) and its new structural analog EC-1 administered
systemically to CBA mice on the immune responsiveness have been examined. Three
main findings are presented in this study. First, the principal effect of SP and
EC-1 on the immunity is a stimulatory one. It is shown that in the doses of 1, 10
and 100 mkg/kg of the body weight both neuropeptides significantly increased the
number of plaque- and rosette-forming cells in the spleen of animals at the peak
of the immune reactions. Second, the destruction of the pituitary stalk prevented
the immune response stimulation caused by neuropeptides. Third, SP-induced
immunostimulation was not observed after combination with the antagonist of the
postsynaptic dopamine (DA) D-2 receptors haloperidol (2 mg/kg) suggesting the
involvement of the DAergic system in the realization of this effect. Thus, these
results demonstrate neurochemical DAergic mechanisms underlying the
immunostimulating influence of tachykinins.
PMID- 9637350
TI - Modulation of the immune response by changing neuromediator systems activity
under stress.
AB - The possible correction of the immune response affecting the mechanisms of
neuroimmunomodulation in the animal model of immobilization stress is considered.
Immobilization (3 h on the back) of CBA mice caused a suppression of the immune
response. The number of plaque-forming cell (PFC) on the 4th day as well as
rosette-forming cell (RFC) number on the 5th day of the immune reaction to sheep
red blood cells (SRBC) were found to be reduced as compared to the control.
Immunoinhibition in the stressed mice was reversed by the depletion of the
cerebral serotonin (5-HT) with p-chlorophenylalanine (PCPA) 2 days before
immobilization at a dose of 500 mg/kg. Activation of postsynaptic D-1 and D-2
dopamine (DA) receptors with apomorphine administered 30 min before stress
attenuated stress-induced immunosuppression as well. Thus, the immunosuppression
elicited by a stressor can be modified by drugs influencing the 5-HT and DAergic
systems. It is suggested that the stress-provoked alterations of the immune
response can be a consequence of changing neurochemical pattern of the brain and
the disturbances of the mechanisms of psychoneuroimunomodulation.
PMID- 9637351
TI - The immunomodulator OM-89 induces ACTH and glucocorticoid secretion in rats
through an IL-1 dependent pathway.
AB - The immunomodulator OM-89 (bacterial extract from E. coli), known to act on the
immune system by modulating both humoral and cellular responses, significantly
increases ACTH and glucocorticoids secretion in normal Wistar rats. A comparative
administration of IL-1 displays a similar pattern of release. Moreover, OM-89
induced responses are blocked by IL-1ra, the soluble receptor antagonist of IL-1.
The effect of OM-89 can thus be explained, at least in part, via IL-1 which
directly enhances the secretion of both stress hormones. Finally, a comparative
experiment between control and stressed rats (by immobilization) shows that the
responses to OM-89 measured in this study (ACTH and corticosterone secretion) are
stress-modulated.
PMID- 9637352
TI - Bacterial cell wall components as immunomodulators--I. Lipopeptides as adjuvants
for parenteral and oral immunization.
AB - We investigated the immunostimulatory properties of synthetically prepared
lipopeptides derived from the cell wall of Gram negative bacteria. These
compounds constitute potent macrophage activators and polyclonal B-lymphocyte
stimulators. They are also immunoadjuvants in parenteral or oral immunization. By
coupling the lipopeptides to haptens or low molecular weight antigens which are
not immunogenic per se, highly immunogenic conjugates can be prepared.
Lipopeptide antigen conjugates as synthetic vaccines give protection by enhancing
the antibody-mediated immune response, and they stimulate the cellular immune
response in vivo by priming of cytotoxic T-cells.
PMID- 9637353
TI - Bacterial cell wall components as immunomodulators--II. The bacterial cell wall
extract OM-85 BV as unspecific activator, immunogen and adjuvant in mice.
AB - The bacterial extract Broncho-Vaxom used for the prevention and treatment of
recurrent respiratory tract infections is an immunomodulator in vitro and in
vivo, as determined in a murine model. The extract acts, on the one hand, as
macrophage activator and polyclonal B-lymphocyte stimulant. On the other hand,
after repeated intraperitoneal or oral immunizations, the extract is immunogenic,
inducing serum IgG binding to the bacterial strains used for the preparation of
the extract. On bacteria, the sera recognize the cell wall components porin,
lipoprotein/lipopeptide and murein. The bacterial extract also exhibits adjuvant
properties when applied in mixture with antigens, such as TNP-BSA or an influenza
vaccine preparation. The unspecific and the immunospecific stimulatory effect of
the extract as well as its adjuvant properties could be of importance for
understanding its therapeutic effect.
PMID- 9637354
TI - In vivo study on the immunomodulating effects of OM-85 BV on survival,
inflammatory cell recruitment and bacterial clearance in Klebsiella pneumonia.
AB - Oral administration of the bacterial extract OM-85 BV has been shown to prime
alveolar macrophages (AM) in such a way that they secrete significantly more
nitric oxide, tumor necrosis factor-alpha and interleukin-1beta upon in vitro
stimulation with lipopolysaccharide (LPS). As increased cytokine secretion by AM
may account for the therapeutic effect of OM-85 BV in respiratory tract
infections, we studied the effect of orally administered OM-85 BV on the outcome
of Klebsiella pneumoniae-induced pneumonia. Mice received a daily oral dose of OM
85 BV (350 mg/kg body weight) for 5 days and were intratracheally infected with
333, 1000 or 3333 CFU K. pneumoniae on day 8. It was shown that OM-85 BV
pretreatment of mice has no effect on bacterial clearance, neutrophil recruitment
and survival in this acute respiratory tract infection. Also, OM-85 BV treatment
had no protective effect in a recurrent infection with K. pneumoniae. It is
concluded that AM activation by oral treatment with OM-85 BV is not sufficient to
play a protective role in respiratory tract infection with K. pneumoniae.
PMID- 9637355
TI - Antirheumatic E. coli extract OM-89 induces T cell responses to HSP60 and 70.
AB - Oral administration of E. coli extract OM-89 is used in treating RA. It has been
shown that immune reactivity to heat-shock proteins (hsp) is involved in
immunomodulation of arthritis. We evaluated the postulated presence and
immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis
were analyzed. Proliferative T cell responses to bacterial hsp60 and hsp70 were
found in rats immunized with OM-89. And conversely, immunization with hsp
antigens induced OM-89-specific T cell responses. Hsp70 (DnaK) was found to be a
major immunogenic constituent of OM-89. Parenteral immunization with OM-89
reduces resistance to adjuvant arthritis (AA), whereas oral administration
protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA
our findings suggest peripheral tolerance induced by hsp-specific regulatory T
cells as a mode of action for OM-89 as an arthritis suppressive oral drug.
PMID- 9637356
TI - Oral dosing of rats with OM-89 results in the appearance of specific OM-89
antibodies of the IgG2a isotype: possible significance in the treatment of
rheumatoid arthritis.
AB - OM-89 is a glycoprotein-rich extract of Escherichia coli shown to be effective in
the treatment of rheumatoid arthritis (RA). It has been reported that oral dosing
of animals results in the appearance of specific OM-89 antibodies. In the current
study we have investigated some of the immunoglobulin isotypes that may be
involved. OM-89 antibodies of IgG1, IgG2a and IgM isotypes were measured by ELISA
in serum from rats dosed three times a week for 3 weeks at 4 or 40 mg kg(-1). The
results showed a small but significant rise in IgM and a greater rise in IgG2a.
The possibility that antigens within OM-89 (e.g. hsp65) may have homology with
antigens involved in RA raises the possibility that OM-89 antibodies,
particularly of the IgG2 class, may block pathogenic antigens from being
recognized by T cells.
PMID- 9637357
TI - Intervention in autoimmune diabetes by targeting the gut immune system.
AB - BB rats and nonobese diabetic (NOD) mice spontaneously develop autoimmune insulin
dependent diabetes and serve as models for human type I diabetes. During
progression of the disease the cytokine pattern elaborated by islet infiltrating
immune cells shifts from a Th2 or Th0 toward Th1 type. Only the latter is
associated with "destructive" insulitis. We discuss here attempts to modulate
disease progression by targeting the gut immune system with bacterial
immunostimulants. Oral dosing of diabetes prone BB rats with lipopolysaccharide
(LPS) or the Escherichia coli extract OM-89 lead to a Th2-shift of pancreatic
mRNA expression. In vitro studies showed that repeated exposure toward LPS or OM
89 lead to downregulation of proinflammatory macrophage responses. In the NOD
mouse, repeated oral dosing of OM-89 caused a Th2 shift in the gut cytokine gene
expression, probably because of desensitization of macrophages and other antigen
presenting cells. Concomitantly, diabetes prevention by oral insulin was
improved. In conclusion, oral dosing with bacterial immunostimulants dampens Th1
type immune reactivities of the gut immune system and thereby promotes oral
tolerance mechanisms. Downregulation of proinflammatory immune reactivities by
repeated exposure to bacterial stimulants requires intact desensitization
mechanisms in macrophages or other antigen presenting cells.
PMID- 9637358
TI - Molecular mechanisms of the immunosuppressive action of cyclosporin A.
PMID- 9637359
TI - Immunomodulatory properties of antiviral acyclic nucleotide analogues: cytokine
stimulatory and nitric oxide costimulatory effects.
AB - Acyclic nucleotide analogues exhibit strong activity against a broad range of
viruses, including HIV-1 and -2. We have investigated their effects on in vitro
secretion of cytokines and production of nitric oxide (NO) by murine peritoneal
macrophages, factors known to play a role in virus replication. Included in the
study were the most prominent compounds of the series: 9-(2
phosphonomethoxyethyl)adenine, 9-(2-phosphonomethoxyethyl)-2,6-diaminopurine, the
(R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl) adenine [(R)- or (S)
PMPA], (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl)-2,6-diaminopurine
[(R)- or (S)-PMPDAP], 9-(2-phosphonomethoxyethyl)guanine (PMEG), and (S)
enantiomer of 1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine [(S)-HPMPC]. PMEG,
(R)-PMPA, and (S)-PMPA greatly enhanced the secretion of both tumour necrosis
factor-alpha (TNF-alpha) and interleukin-10 (IL-10), (R)-PMPDAP stimulated only
TNF-alpha, other test compounds were ineffective. None of them influenced the
secretion of IL-2 or interferon-gamma (IFN-gamma). Both TNF-alpha and IL-10 have
been found to be major factors determining enhancing effects of PMEG, (R)-PMPA,
and (S)-PMPA on production of NO generated by exogenous IFN-gamma. The study
points to a possible implication of immunomodulatory properties in the antiviral
effects of some acyclic nucleotide analogues. In addition, our data support the
view that endogenous IL-10 can stimulate certain macrophage functions.
PMID- 9637360
TI - Possible dual role of nitric oxide in oxidative stress injury: a study in
perfused hepatocytes.
AB - Nitric oxide (NO) is a multifunctional messenger in many vertebrates. In the
liver, NO was found to play an important but controversial role in injury
produced by toxins or sepsis. The purpose of the present investigation was to
further characterize the role of NO in hepatocyte oxidative injury. A cellular
system formed of immobilized and perfused rat hepatocytes was used to test the
ability of the latter to produce endogenous NO after lipopolysaccharide
administration in vivo (LPS, 20 mg/kg i.p.) and how hepatocyte functionality
competence is modified according to NO level. This cellular system also was used
to delineate a relationship between exogenously delivered NO to the perfusion
medium as produced by the NO donor, sodium nitroprusside (2.0 and 0.2 mM), and
any alteration in the degree of injury as evoked by anoxia/reoxygenation or
cumene hydroperoxide (1.0 mM and 0.2 mM). Rat hepatocytes were immobilized in low
gelling agarose and perfused with Williams E medium. Endogenous or exogenous NO
was evaluated by measuring the end products of NO (NO2- + NO3-) in the perfusion
medium. Functional integrity of hepatocytes was evaluated from lactate
dehydrogenase (LD) leakage, urea synthesis in the perfusion medium and lipid
peroxides (LP) formation. Normal, anoxia/reoxygenation or cumene hydroperoxide
injured hepatocytes did not exhibit measurable NO while LPS-treated hepatocytes
produced NO. Apparently, within the present experimental conditions, it seems
that there was an inverse relation between the rate of NO produced after LPS
administration and the rate of lipid peroxides formed in the hepatocytes. Low
concentration of sodium nitroprusside (as NO donor) significantly decreased LD
leakage, increased the rate of urea synthesis and increased trypan blue exclusion
by hepatocytes in anoxia/reoxygenation or cumene hydroperoxide injured (0.2 mM)
cells. Lipid peroxides were decreased by NO in cumene hydroperoxide injured
hepatocytes. The present data suggest that NO endogenously produced, or
exogenously delivered, has an ameliorative role in mild oxidative liver injury
models, but not in severe cases and that inside hepatocytes, there is a very
delicate balance between the rate of NO production and its consumption. The
disturbance in this balance may be responsible for injury due to the formation of
more toxic oxygen species.
PMID- 9637361
TI - Glucan as stimulator of hematopoiesis in normal and gamma-irradiated mice. A
survey of the authors' results.
AB - Glucan, a beta-1,3-linked polyglucose derived from the yeast Saccharomyces
cerevisiae, is a broad spectrum enhancer of host defense mechanisms stimulating
humoral and cell-mediated immunity. On the basis of these features, glucan has
been tested by the authors' research group in experiments on gamma-irradiated
mice. Two glucan forms, particulate and soluble, have been studied. Attention has
been focused on various application regimens in relation to the time of
irradiation (pre- or postirradiation application), the possibilities of using
glucan in various radiation regimens (single or repeated irradiation), combined
pharmacological therapy (joint administration of glucan with cystamine or
inhibitors of prostaglandin synthesis), and on the negative side effects of
therapy with glucan. Some studies included also experiments on unirradiated mice.
The results have demonstrated the ability of glucan to influence positively the
course of the acute radiation disease. Stimulation of hematopoiesis has been
found to be the most important mechanism of glucan's radioprotective effects. In
this communication, the results of 11 full-length articles are summarized and
discussed.
PMID- 9637362
TI - Stimulation of haemopoiesis and protection of mice against radiation injury by
synthetic analogues of muramyldipeptide incorporated in liposomes.
AB - Protection from undesirable effects of radiotherapy or chemotherapy, primarily
from myelosuppression, remains still a crucial problem to be studied. Attention
has been therefore paid to various immunomodulatory agents that through the
monocyte/macrophage system induced production of cytokines, which can induce and
operate restoration of haemopoiesis and thus act radioprotectively. Some
synthetic analogues of MDP free of undesirable side-effects, were synthesized in
the Czech Republic. Lipophilic beta-D-GlcNstearoyl-(1- > 4)-norMurNAc-L-Abu-D
isoGln (DDD-St) was designed to be easily entrapped into liposomes and this
liposomal DDD-St protected efficiently mice against irradiation, when
administered i.p., i.v. or s.c. 24 h prior to lethal irradiation (survival rate
in the range of 30-80% compared with 0% in control). Especially the subcutaneous
application of liposomal DDD-St was very efficient. The parameters characteristic
of recovery of haemopoiesis in bone marrow on day 10 after 6.5 Gy irradiation
were significantly improved in comparison with the controls. Very high
radioprotective effect of s.c. administered liposomal DDD-St can be explained
(together with induction of haemopoiesis) by an effective and long-lasting
activation of nonspecific immunity, which is able to withhold an onset of
septicemia in early days after irradiation. In conclusion, the liposomal DDD-St
should be therapeutically beneficial in moderating the haemopoietic damage, which
is an undesirable effect of radiotherapy or chemotherapy.
PMID- 9637363
TI - Hugh Alistair Reid OBE MD: investigation and treatment of snake bite.
AB - Alistair Reid was an outstanding clinician, epidemiologist and scientist. At the
Penang General Hospital, Malaya, his careful observation of sea snake poisoning
revealed that sea snake venoms were myotoxic in man leading to generalized
rhabdomyolysis, and were not neurotoxic as observed in animals. In 1961, Reid
founded and became the first Honorary Director of the Penang Institute of Snake
and Venom Research. Effective treatment of sea snake poisoning required specific
antivenom which was produced at the Commonwealth Serum Laboratories in Melbourne
from Enhydrina schistosa venom supplied by the Institute. From the low frequency
of envenoming following bites, Reid concluded that snakes on the defensive when
biting man seldom injected much venom. He provided clinical guidelines to assess
the degree of envenoming, and the correct dose of specific antivenom to be used
in the treatment of snake bite in Malaya. Reid demonstrated that the non-clotting
blood of patients bitten by the pit viper, Calloselasma rhodostoma [Ancistrodon
rhodostoma] was due to venom-induced defibrination. From his clinical experience
of these patients, Reid suggested that a defibrinating derivative of C.
rhodostoma venom might have a useful role in the treatment of deep vein
thrombosis. This led to Arvin (ancrod) being used clinically from 1968. After
leaving Malaya in 1964, Alistair Reid joined the staff of the Liverpool School of
Tropical Medicine, as Senior Lecturer. Enzyme-linked immunosorbent assay (ELISA)
for detecting and quantifying snake venom and venom-antibody was developed at the
Liverpool Venom Research Unit: this proved useful in the diagnosis of snake bite,
in epidemiological studies of envenoming patterns, and in screening of antivenom
potency. In 1977, Dr H. Alistair Reid became Head of the WHO Collaborative Centre
for the Control of Antivenoms based at Liverpool.
PMID- 9637364
TI - Characterization of mastoparan-induced histamine release from RBL-2H3 cells.
AB - Mastoparan (5-30 microM), a tetradecapeptide isolated from wasp venom, caused
histamine release from RBL-2H3 cells in a concentration- and time-dependent
manner. Mastoparan-induced histamine release remained after removing the
extracellular Ca2+, whereas the antigen-induced one disappeared. Pertussis toxin
did not inhibit mastoparan-induced histamine release from the cells, and
mastoparan did not stimulate phosphoinositide hydrolysis. In agreement with the
results, RBL-2H3 cells had a small amount of ADP-ribosylation substrates for
pertussis toxin. Neomycin (1-5 mM) suppressed mastoparan-induced histamine
release and phospholipase D activation. However, butanol slightly inhibited
mastoparan-induced histamine release. Moreover, 2,3-diphosphoglycerate inhibited
mastoparan-induced phospholipase D activation, but not it's histamine release. On
the other hand, mastoparan caused the leakage of lactate dehydrogenase from the
cells in a similar concentration range to the histamine release. This leakage was
also suppressed by neomycin. These results suggest that mastoparan enhances the
membrane permeability, resulting in histamine release in a pertussis toxin
insensitive manner, and that mastoparan-induced phospholipase D activation may
not relate to histamine release.
PMID- 9637365
TI - Characterization of three fibrinogenolytic enzymes from Chinese green tree viper
(Trimeresurus stejnegeri) venom.
AB - From the venom of Chinese green tree viper (Trimeresurus stejnegeri), three
distinct fibrinogenolytic enzymes: stejnefibrase-1, stejnefibrase-2 and
stejnefibrase-3, were purified by gel filtration, ion-exchange chromatography and
reverse-phase high-performance chromatography (HPLC). SDS-PAGE analysis of those
three enzymes showed that they consisted of a single polypeptide chain with mol.
wt of 50000, 31000 and 32000, respectively. Like TSV-PA (a specific plasminogen
activator) and stejnobin (a fibrinogen-clotting enzyme) purified from the same
venom, stejnefibrase-1, -2 and -3 were able to hydrolyze several chromogenic
substrate. On the other hand, different from TSV-PA and stejnobin, stejnefibrase
1, -2 and -3 did not activate plasminogen and did not possess fibrinogen-clotting
activity. The three purified enzymes directly degraded fibrinogen to small
fragments and rendered it unclottable by thrombin. Stejnefibrase-2 degraded
preferentially Bbeta-chain while stejnefibrase-1 and -3 cleaved concomitantly
Aalpha and Bbeta-chains of fibrinogen. None of these proteases degraded the gamma
chain of fibrinogen. When correlated with the loss of clottability of fibrinogen,
the most active enzyme was stejnefibrase-1. The activities of the three enzymes
were inhibited by phenylmethylsulfonyl fluoride (PMSF) and p-nitrophenyl-p
guanidinobenzoate (NPGB), indicating that like TSV-PA and stejnobin, they are
venom serine proteases.
PMID- 9637366
TI - Role of free thiol groups in the biological activities of stonustoxin, a lethal
factor from stonefish (Synanceja horrida) venom.
AB - Stonustoxin (SNTX) is a two-subunit protein purified from the venom of a
stonefish, Synanceia horrida. It has potent lethal activity and is also a
membrane pore-forming cytolysin. The role of thiol groups in the biological
activities of SNTX was investigated. Both the hemolytic and lethal activities of
SNTX were potentiated by the reducing agent, dithiothreitol (DTT). The hemolytic
activity of SNTX was sensitive to the modification of thiol groups by 5,5'
dithiobis(2-nitrobenzoic acid) (DTNB). The loss of haemolytic activity correlated
with the number of thiol groups that were titrated with DTNB. Thiol modification
of SNTX with DTNB also inhibited its lethality. These inhibitory effects of thiol
modification could be reversed by reduction with DTT. It was also found that the
haemolytic activity of SNTX could not be inhibited by cholesterol. These
observations indicate that free thiol groups play an important role in the
haemolytic activity and lethality of SNTX but unlike other thiol-activated
cytolysins, SNTX was not inhibited by cholesterol. Thus, SNTX may represent a new
class of cytolytic toxin.
PMID- 9637367
TI - Isolation and partial characterisation of highly toxic lectins from Abrus
pulchellus seeds.
AB - The seeds of Abrus pulchellus, sub-specie tenuiflorus, belonging to the
Leguminosae, subfamily Papilionoideae contain highly toxic lectins exhibiting
specificity for galactose and galactose-containing structures. The toxins which
agglutinate rabbit erythrocytes, present a highly toxic activity in vivo when
injected in the peritoneal cavity of mice (LD50=31 microg x kg(-1)) or when
tested with the microcrustacean Arthemia salina (LD50=3.5 microg x ml(-1)). The
active fraction was purified in a single step, by affinity chromatography on a
Sepharose-4B column. The purified toxins migrated as two single bands of Mr 63000
and 61500 Da (SDS-PAGE) and Mr 31500 and 29000 Da (SDS-PAGE with 2
mercaptoethanol), respectively, suggesting the presence of disulphide-bridge
interchains as occurs in other plant toxins. The antibodies anti-A. pulchellus
toxins did not recognize ricin preparation and only partial identity was observed
to A. precatorius toxic lectins prepared in a similar way to ricin and A.
pulchellus toxins.
PMID- 9637368
TI - Structural characterization of a new acylpolyaminetoxin from the venom of
Brazilian garden spider Nephilengys cruentata.
AB - The use of mass spectrometry, in which high-energy CID and charge remote
fragmentation both of protonated and sodium-attached molecular ions was applied,
afforded the structural elucidation of a new acylpolyaminetoxin with Mw=801 Da
from the venom of the Brazilian garden spider Nephilengys cruentata. In spite of
having the same Mw of the NPTX-2, previously described in the venom of the Joro
spider Nephila clavata, neither toxins are isomers. In order to differentiate
them by using the most usual nomenclature, the new toxin was named NPTX-801C and
the NPTX-2 was renamed to NPTX-801E. Both toxins have as common structure the 4
hydroxyindole-3-acetyl-asparaginyl-cadaveryl moiety in their molecules and their
structure may be represented in a simplified way: NPTX-801E is HO-indole-Asn-Cad
Pta-Orn-Arg and NPTX-801C is HO-indole-Asn-Cad-Gly-Put-Pta-Pta.
PMID- 9637369
TI - Effects of Russell's viper venom on renal lysosomal functions in experimental
mice.
AB - The lysosome-enriched fraction of mice kidney was isolated by homogenization and
differential centrifugation. Lysosomal functions, namely lysosomal enzyme
activities and membrane integrities were investigated in (a) the renal lysosome
enriched fraction, incubated with different concentrations of Russell's viper
venom (RVV) for various time intervals (in vitro test) and (b) the kidney
homogenate of mice, which had been envenomed with different dosages of RVV and
been sacrificed after various time intervals post-envenomation (in vivo test).
Three typical marker enzymes for lysosome were used, namely N-acetyl-beta-D
glucosaminidase (NAG), cathepsin D and acid phosphatase. It was found that, with
increasing dosages of RVV and increasing time intervals after RVV treatment, the
activities of all lysosomal enzymes generally increased and the lysosomal
membrane integrities apparently reduced in in vitro and in vivo conditions,
respectively. Among the three typical marker enzymes, NAG was found to be the
most specific, sensitive and informative marker enzyme for the study of lysosomal
functions in the kidney of mice treated with RVV.
PMID- 9637370
TI - A rapid procedure for the isolation of the Lys-49 myotoxin II from Bothrops
moojeni (caissaca) venom: biochemical characterization, crystallization, myotoxic
and edematogenic activity.
AB - Bothtrops moojeni snake venom was fractionated on a CM-Sepharose column which was
previously equilibrated with 0.05 M ammonium bicarbonate buffer at pH 8.0 and
subsequently eluted with an ammonium bicarbonate concentration gradient from 0.05
to 0.5 M at constant pH (8.0) and temperature (25 degrees C). The fraction which
eluted last (M-VI) showed, after direct lyophilization, a single band by
polyacrylamide gel electrophoresis (PAGE) and SDS-PAGE, indicating an approximate
Mr of 14000 and 27000, in the presence and absence of dithiothreitol,
respectively. Its amino acid composition revealed a high level of hydrophobic and
basic amino acids as well as 14 half-cystine residues. Its isoelectric point and
extinction coefficient (E(1.0 mg/ml) (1.0 cm) at 278 nm and pH 7.0) were 8.2 and
1.170, respectively. M-VI was devoid of phospholipase A2 (PLA2) activity on egg
yolk, as well as of hemorrhagic, anticoagulant and coagulant activities, but
could induce drastic necrosis on skeletal muscle fibres as well as rapid and
transient edema on the rat paw. Its N-terminal sequence:
SLFELGKMILQETGKNPAKSYGVYGCNCGVGGRGKPKDATDRCCYVHKCCYK... revealed high homology
with other Lys 49 PLA2-like myotoxins from other bothropic venoms. Orthorhombic
crystals of M-VI, which diffracted to a maximal resolution of 1.6 A, were
obtained and indicated the presence of a dimer in the asymmetrical unit.
PMID- 9637371
TI - Transmission of the paralytic shellfish poisoning toxins, from dinoflagellate to
gastropod.
AB - Purple clams, Hiatula diphos Linnaeus, are filter-feeding bivalves and maculated
ivory shells. Babylonia areolata Link are carnivorous gastropods. Both
shellfishes are popular seafood delicacies among the Taiwanese. Hiatula diphos
were forced to contain gonyautoxins (GTXs) in this research by feeding them with
cells of Alexandrium minutum Halim, a toxic dinoflagellate species responsible
for the paralytic shellfish poisonings in Taiwan. The intoxicated purple clams of
known toxicity and toxin composition were fed to B. areolata to observe the
transmission and transformation of GTXs among this shellfish. It was found that
the toxin composition in bivalve and gastropod were similar to that in
dinoflagellate. Our data provide evidence for food-chain transmission of
paralytic shellfish poisoning toxins, from dinoflagellate to gastropod through a
filter-feeding bivalve. The transmitted GTX-I. -II. -III and -IV of A. minutum
could only be found in the viscera of these shellfish. There was a notable
degradation of GTX-I in the ivory shell that resulted in a decrease in toxicity
while the total amount of toxins was accumulatively increasing.
PMID- 9637372
TI - The involvement of plasma kinins in the cardiovascular effects of Leiurus
quinquestriatus scorpion venom in anaesthetised rabbits.
AB - The present study was undertaken to investigate the involvement of kinins in the
cardiovascular- and respiratory effects of LQQ venom. Blood pressure, heart rate,
electrocardiogram (ECG) and respiration were studied in anaesthetised rabbits, in
the presence and absence of aprotinin and icatibant, a B2 bradykinin antagonist.
Plasma bradykinin concentrations were also measured following venom injection.
LQQ venom caused a triphasic effect on blood pressure comprising an immediate
fall, a pronounced rise and a progressive decline until death. Bradycardia,
myocardial damage, arrhythmias, respiratory distress and pulmonary oedema were
also exhibited. Pretreatment with aprotinin attenuated the venom-induced
hypotension, bradycardia, ECG and respiratory changes and prolonged survival.
Pretreatment of atropinized animals with icatibant gave similar protection. In
animals treated with LQQ venom, plasma bradykinin was significantly higher than
controls, although there was considerable inter-animal variation in plasma kinin
concentrations and the elevation was seen relatively late after venom
administration. The data provides some support for the hypothesis that kinins are
involved in the cardiovascular and lethal effects of LQQ venom in rabbits.
PMID- 9637373
TI - Sphingomyelinase D activity of brown recluse spider (Loxosceles reclusa) venom as
studied by 31P-NMR: effects on the time-course of sphingomyelin hydrolysis.
AB - The time-course for the hydrolysis of the D linkage of chicken egg yolk
sphingomyelin in a Triton X-100 mixed micelle and of lysophosphotidylcholine
micelles, as catalyzed by brown recluse spider venom and brown recluse spider
toxin, was followed by phosphorous-31 nuclear magnetic resonance spectroscopy.
The overall rate of hydrolysis of sphingomyelin in mixed micelles was found to be
an order of magnitude faster than the hydrolysis of lysophosphotidylcholine.
Incorporation of lysophosphotidylcholine into mixed micelles with Triton X-100
inhibited the lipase activity of brown recluse spider venom and brown recluse
spider venom toxin. The effects of increased rates of overall reaction were
observed with increased temperature and also with decreased ionic strength. The
presence of divalent calcium ions was found to be necessary for hydrolytic
activity, but only in catalytic amounts (less than 1 mM).
PMID- 9637374
TI - Crystallization of piratoxin I, a myotoxic Lys49-phospholipase A2 homologue
isolated from the venom of Bothrops pirajai.
AB - Large single crystals of piratoxin I. a Lys49-PLA2 homologue with low enzymatic
activity, have been obtained. The crystals belong to the orthorhombic system
space group P2(1)2(1)2(1), and diffract X-rays to a resolution of 2.8 A.
Preliminary analysis reveals the presence of two molecules in the
crystallographic asymmetric unit.
PMID- 9637375
TI - Bibliography of toxinology.
PMID- 9637376
TI - Welfare of the competition horse.
PMID- 9637377
TI - International disease surveillance: summary of outbreaks of the major diseases in
Europe in 1997.
PMID- 9637378
TI - Determination of the frequency and distribution of vascular and parenchymal
amyloid with polyclonal and N-terminal-specific PrP antibodies in scrapie
affected sheep and mice.
AB - Brains from 17 histopathologically confirmed cases of scrapie, five of which had
congophilic vascular amyloid, were stained immunohistochemically for prion
protein (PrP) using a polyclonal antibody. Two clinically suspect but
pathologically unconfirmed cases of natural sheep scrapie and the brains of four
mice infected with the 111A murine scrapie strain were also examined. Selected
sections containing amyloid were stained with each of two peptide antibodies
which recognise the N-terminal amino acid residues which are lost following
protease digestion of the disease-specific isoform of PrP. The mice infected with
the 111A murine scrapie strain had large numbers of hypermature plaques. All the
amyloid plaques from both natural sheep scrapie brains and experimental murine
brains were heavily immunostained by the polyclonal and both peptide antibodies.
In addition, disease-specific accumulations of PrP were detected in endothelial
cells or in the intima of blood vessels of the cerebral cortex of sheep scrapie
brains. The affected blood vessels were located in areas which otherwise lacked
typical scrapie pathology. Vascular accumulations of PrP were also found in
leptomeningeal and choroid plexus blood vessels. Vascular amyloid was found
mainly in the neocortex. Vascular amyloid and disease-specific parenchymal
accumulations of PrP were found in two sheep which showed clinical signs of
scrapie but lacked its typical vacuolar pathology. These results show that the
mature amyloid of scrapie is composed of, or contains a substantial proportion
of, whole length PrP protein. Thus truncation of PrP is not essential for the
aggregation of PrP into amyloid. The vascular amyloid of natural sheep scrapie
originates from the accumulation and release of PrP from endothelial cells
presumably following systemic scrapie infection. The topography of vascular
amyloid distribution in Great Britain differs from that reported in the
Netherlands. As amyloid deposition in mice is largely controlled by the strain of
the infecting agent it is possible that the strain of the agent may influence
vascular amyloid deposition.
PMID- 9637379
TI - Haemorrhagic smolt syndrome: a severe anaemic condition in farmed salmon in
Scotland.
AB - Farmed pre-smolt stage Atlantic salmon developed an acute, severe haemorrhagic
anaemia, termed haemorrhagic smolt syndrome. The fish were in good condition, but
lethargic, and had widespread visceral and muscle petechiation and ecchymoses.
The mean (sd) haematocrit of affected fish was 1.4(0.9) per cent and
histopathology revealed widespread haemorrhage in all organs, associated with
endothelial tissue. No infectious agent was isolated and the condition could not
be transmitted experimentally. The clinical evidence indicates that the condition
is non-infectious, but its aetiology could not be fully established.
PMID- 9637380
TI - Comparison of detomidine/ketamine and guaiphenesin/thiopentone for induction of
anaesthesia in horses maintained with halothane.
AB - This prospective clinical study compared the physiological effects of two
commonly used anaesthetic induction techniques in horses maintained with
halothane. One hundred horses admitted for elective surgery were randomly
allocated to receive either guaiphenesin (to effect) and thiopentone (5 mg/kg),
or detomidine (20 microg/kg) and ketamine (2 mg/kg) for the induction of
anaesthesia after acepromazine premedication. Anaesthesia was maintained with
halothane in oxygen. There were no significant differences in breed, age, sex,
weight, type of surgery and duration of anaesthesia between the groups.
Immediately after induction of anaesthesia heart rate was higher after
guaiphenesin and thiopentone, and arterial blood pressure was higher after
detomidine and ketamine. Thereafter hypotension, often necessitating an infusion
of dobutamine, developed in both groups. Arterial blood gases and respiratory
rates were similar in the two groups. There were no significant differences
between the groups in the subjectively scored quality of induction and recovery,
or in recovery time.
PMID- 9637381
TI - Assessing abattoir hygiene with a marker organism.
AB - A study was made to evaluate the use of a marker organism for assessing whether
hygienic slaughter practices were being followed at red meat abattoirs. The
organism, a nonpathogenic strain of Escherichia coli K12 that was resistant to
nalidixic acid, was detected and counted on a highly specific isolation medium.
With beef carcases, the practice of bagging the excised anus reduced, but did not
prevent the spread of the organism from an inoculum applied in the anal region
before the hide was removed. The carcases of sheep that were processed at a low
throughput abattoir, were contaminated with the marker after the fleece had been
inoculated at a single site. The contamination was significantly reduced
(P<0.001) when the operative responsible for flaying had cleaned his hands, arms
and apron before and during the handling of each carcase, and used a knife which
was freshly pasteurised on several occasions. However, the subsequent washing of
carcases had little or no effect on the levels of the marker organism. It was
concluded that the marker may be of value in assessing hygiene control, improving
present practices, and training abattoir staff.
PMID- 9637382
TI - Diabetes mellitus in dogs: a study of the critical difference for canine serum
fructosamine.
AB - The purpose of this study was to calculate the critical difference between two
analytical measurements of serum fructosamine concentration in dogs. The critical
difference can be used to judge whether the difference between two consecutive
analytical results from the same animal is due to natural variation. Blood
samples from 15 apparently clinically healthy beagle dogs were collected once a
week for six consecutive weeks. The serum fructosamine concentration was measured
by the reduction test with nitroblue tetrazolium and the critical difference was
calculated from the component of variance for weeks within dogs (sigma2s) and the
residual variance (sigma2e). The critical difference between two consecutive
analytical results was 33.5 micromol/litre.
PMID- 9637383
TI - Warble fly status of Great Britain in 1997.
PMID- 9637384
TI - Salinomycin toxicity in layer breeders.
PMID- 9637385
TI - Treatment of a uterine adenocarcinoma in a domestic rabbit by ovariohysterectomy.
PMID- 9637386
TI - Nasal mite of dogs Pneumonyssus (Pneumonyssoides) caninum in Iran.
PMID- 9637387
TI - Staffing at veterinary schools.
PMID- 9637388
TI - Staffing at veterinary schools.
PMID- 9637389
TI - Staffing at veterinary schools.
PMID- 9637390
TI - Influence of sample collection on bulk tank somatic cell count.
PMID- 9637391
TI - Gas gangrene in a horse.
PMID- 9637392
TI - Aorto-iliac thrombosis in calves.
PMID- 9637393
TI - Fumes from gas boilers.
PMID- 9637394
TI - Veterinary Benevolent Fund.
PMID- 9637395
TI - Protective effect of deferoxamine on sodium nitroprusside-induced apoptosis in
PC12 cells.
AB - Reportedly, the generation of nitric oxide (NO) may lead to iron mobilization
from ferritin disrupting intracellular iron homeostasis and increasing levels of
reactive oxygen species. In the present study, we evaluated the role of
endogenous iron in NO-induced apoptosis in PC12 cells. Apoptosis was tested by
flow cytometry, fluorescence microscopy and terminal deoxynucleotidyl transferase
mediated 2'-deoxy-uridine 5'-triphosphate nick end labeling (TUNEL) technique.
Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. When incubated with 0.5-0.75 mM sodium
nitroprusside (SNP, a chemical NO donor), PC12 cells were shown to undergo
apoptosis. In addition, SNP induced a time-dependent decrease in cell viability.
Since deferoxamine (0.05-0.1 mM), a powerful iron chelator, inhibited both SNP
induced apoptosis and the decrease in cell viability, we suggest that these NO
effects may be dependent upon iron mobilization within the cell.
PMID- 9637396
TI - Comparable activity levels in developmentally deprived and non-deprived layer IV
cortical columns of the adult rat primary somatosensory cortex.
AB - It has been suggested that evoked neural activity levels promote the selective
construction of the primary somatosensory cortex (S1) neuropil. Sensory
deprivation after S1 formation has, however, no effects on its postnatal growth.
This indicates that S1 neuropil elaboration is independent from the ongoing
levels of evoked cortical activity, and/or that sensory deprivation does not
reduce overall levels of S1 evoked activity. We thus indirectly evaluated chronic
and acute levels of neural activity in the developmentally, sensory deprived
adult S1. Relative succinic dehydrogenase activity and 3H2-deoxyglucose uptake
were comparable in control and deprived barrels. Our observations support the
idea that normal levels of evoked neural activity prevent atrophic changes in the
developmentally deprived adult S1. They can not rule out, however, that early
selective S1 neuropil construction occurs independent from evoked neural activity
levels.
PMID- 9637397
TI - Increased dentate granule cell neurogenesis following amygdala kindling in the
adult rat.
AB - Structural neuronal network plasticity is associated with epileptogenesis during
limbic kindling, but the full extent of network changes is not well understood.
We investigated whether dentate granule cell (DGC) neurogenesis, which continues
into adulthood in the rodent, is altered in the amygdala kindling model of
epileptogenesis. Adult rats were stimulated to either 4-6, 9-10 or 19-20 class
4/5 (generalized) kindled seizures. 5-Bromo-2'-deoxyuridine labeling showed that
cell proliferation increased in the dentate gyrus only in animals that
experienced nine or more class 4/5 kindled seizures. Immunocytochemistry for
neuronal markers revealed that many of the newly generated cells differentiated
into DGCs in the inner aspect of the DGC layer. The lack of increased DGC
neurogenesis after fewer kindled seizures or at early timepoints following
kindling suggests that this process is not involved in kindling development.
Instead, newly generated DGCs may be important for maintenance of the kindled
state or the increased susceptibility to spontaneous recurrent seizures.
PMID- 9637398
TI - Self-sustained firing of human motor units.
AB - Motoneurons of invertebrates and vertebrates can continue to fire repetitively
after being activated by a brief, excitatory synaptic input (self-sustained
firing). This firing behavior is due to the activation of intrinsic, voltage
gated currents which produce sustained regenerative depolarizations (plateau
potentials) of the cell. Examination of these intrinsic cellular properties has
been performed in reduced animal preparations and it is unknown if such self
sustained firing occurs in motoneurons of the intact human. In this paper, we
present evidence of this in the human by using a technique of dual motor unit
recordings. Subjects were instructed to maintain a constant dorsiflexion effort,
and the common synaptic input (e.g. descending drive) onto the tibialis anterior
(TA) motoneuron pool was monitored by recording the firing frequency of a low
threshold 'control' unit. Once the firing rate of the control unit was constant,
vibration of the TA tendon recruited a second 'test' unit which continued to fire
after the vibration (i.e. synaptic input) was removed, even though the firing
rate of the control unit (and thus, the common drive) remained the same or
decreased. Self-sustained firing of motoneurons such as this may reduce the need
for prolonged synaptic input when constant muscle activation is required (e.g.
for postural tone).
PMID- 9637399
TI - Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage
in a gerbil model of global ischemia.
AB - The newly-developed calpain inhibitor, MDL 28170 penetrates the blood-brain
barrier and inhibits brain cysteine protease activity after systemic
administration. This experiment was initiated to determine if the calpain
inhibitor, MDL 28170 could, by these actions, reduce neuronal damage in an animal
model of global cerebral ischemia in the gerbil. The calpain inhibitor, MDL 28170
(50 mg/kg), was initiated at 0.5 and 3 h of recirculation following 5min of
global ischemia. Animals subjected to ischemia but without treatment or with
vehicle treatment served as controls. Evaluation by light microscopy was carried
out on paraffin-embedded brain sections of gerbils which were sacrificed 7 days
post-operatively. The results show that the calpain inhibitor, MDL 28170,
protects against cortical neuronal damage even if the treatment is delayed until
3 h after reperfusion. However, the neuroprotective effect of this agent is less
pronounced in the hippocampal CA1 sector. The results suggest that calpain
mediated proteolysis plays an important role in neuronal death due to ischemia.
However, additional mechanisms by which an increased intracellular calcium
concentration leads to neuronal death may exist.
PMID- 9637400
TI - Chemokine inhibition in rat stab wound brain injury using antisense
oligodeoxynucleotides.
AB - Traumatic injury to the central nervous system (CNS) results in the breakdown of
the blood-brain barrier and recruitment of hematogenous cells at the site of
injury. The role of chemokines in this process has been well recognized and they
have been regarded as promising targets for development of anti-inflammatory
therapies. The expression of monocyte chemoattractant protein (MCP-1), in
particular, has been closely linked to macrophage infiltration following trauma
in rat brain. In this study we determined whether inhibition of MCP-1 following
stab wound injury would reduce macrophage infiltration. Stab wound injured
Sprague-Dawley rats were infused with MCP-1 sense or antisense oligonucleotides
using an Alzet miniosmotic pump (1 microl/h for 3 days). Three days following
injury, widespread gliosis was observed in both groups of rats as judged by glial
fibrillary acidic protein (GFAP) immunoreactivity. Immunohistochemistry showed
significantly less staining for MCP-1 in antisense treated animals. In addition,
the number of macrophages were reduced by 30% in the antisense compared to the
sense treated animals (P < 0.05). These results demonstrate that modulation of
MCP-1 expression in stab wound injury directly affects monocytic infiltration and
provide a basis for MCP-1 inhibition as a therapeutic strategy for controlling
inflammatory events of traumatic brain injury.
PMID- 9637401
TI - Intracerebral source localization of mental process-related potentials elicited
prior to mental sweating response in humans.
AB - We measured the mental sweating response (MSR) and the skin sympathetic nerve
activity (SSNA). Mental arithmetic or recall questions first elicited SSNA and
then elicited MSR. MSR was used as the trigger point of time 0 ms to average
EEGs. The averaged EEGs contained slow wave fluctuations, which occurred 5 s
prior to the MSR onset. The current source locations of the MSR-related
potentials were estimated by EEG dipole tracing method in two subjects. Mental
stress activated the inferior frontal gyrus 5.5 s prior to the MSR and then 0.5 s
later, the lateral part of the hippocampus in a subject, and they activated the
medial part of the amygdala 5 s prior to the MSR in another subject. Indirect
contact of the brain with the mind associated with mental questions was
discussed.
PMID- 9637402
TI - Stochastic determination of the chromosomal region responsible for expression of
human glial fibrillary acidic protein in astrocytic tumors.
AB - Previous investigators have localized the human glial fibrillary acidic protein
(GFAP) gene in the segment 17q21 in chromosome 17. In the present study, we
statistically assessed the association between the allelic status in thirty-three
microsatellite loci and the immunohistochemical expression of GFAP in twenty
human astrocytic tumors. The results demonstrated that the loss of heterozygosity
in only one locus (D17S795 located in 17q21.2) was significantly associated with
the impaired expression of GFAP (P = 0.0280, Pc = 0.0384 by Fisher's exact test).
The adjacent loci located in 17q21.1 and 17q21.3 were not relevant to GFAP
expression. Those data suggest that the critical region responsible for GFAP
expression (coding sequence and regulatory elements) is located close to the
locus D17S795 in the segment 17q21.2.
PMID- 9637403
TI - Low density lipoprotein receptor related protein gene exon 3 polymorphism
association with Alzheimer's disease in Chinese.
AB - Since apolipoprotein E4 (apoE4) is the major genetic risk for late onset
Alzheimer's disease (AD), proteins that interact with apoE might be involved in
AD pathogenesis. Low density lipoprotein receptor related protein (LRP) is an
apoE receptor in the brain. In exon 3 of the LRP gene a polymorphism was found to
be underrepresented in AD compared to normal Caucasian subjects (N). We examined
this polymorphism in Chinese AD and N subjects. The polymorphism frequency in N
was roughly half that reported for Caucasians. Compared to N, the frequency was
significantly decreased in pathologically diagnosed, but not in clinically
diagnosed AD patients. Thus, the role of the LRP exon 3 polymorphism in AD has
now been demonstrated in two ethnic groups, suggesting the importance of LRP in
AD pathogenesis.
PMID- 9637404
TI - NMDA-induced increases in rat brain glutamine synthetase but not glial fibrillary
acidic protein are mediated by free radicals.
AB - Both excitotoxicity and oxidative stress are implicated in the pathophysiology of
central nervous system (CNS) ischaemia-reperfusion injury whereby astrocytes
offer neural protection through the production of endogenous antioxidants and
removal of glutamate from the extracellular milieu. This study investigated
whether exogenous alpha-tocopherol, an antioxidant, could prevent N-methyl-D
aspartate (NMDA)-produced increases of the glial specific proteins, glutamine
synthetase (GS) and glial fibrillary acidic protein (GFAP) in rat brain spheroids
in vitro. NMDA (320 microM; 3 days in vitro (DIV)) was unable to induce lipid
peroxidation in rat brain spheroids implying that excitotoxicity in this system
did not involve substantial free radical formation. However at non-cytotoxic
concentrations, increases in astroglial GS were prevented by alpha-tocopherol
treatment, suggesting a role for ROS in the excitotoxic process. In contrast,
NMDA-induced increases in GFAP remained unchanged by alpha-tocopherol indicating
that oxidative stress may not be involved in reactive gliosis at non-cytotoxic
NMDA concentrations.
PMID- 9637405
TI - Bilaterally independent respiratory rhythms in the decerebrate rat.
AB - In rats, respiratory neurons in the medulla oblongata are arranged in
longitudinally distributed groups that are duplicated on each side of the
neuraxis. Our aim was to determine whether respiratory rhythm is generated
independently by each side. We made a complete mid-sagittal section of the
medulla oblongata, 3.5 mm rostral and 3.5 mm caudal to the obex, in decerebrate,
vagotomized, and paralysed adult rats. Respiratory rhythm, monitored by recording
the activity of both left and right phrenic nerves, was maintained and became
asynchronous between the left and right sides. We concluded that in the adult rat
each half of the medulla oblongata is capable of generating respiratory rhythm
independently.
PMID- 9637406
TI - High frequency of apolipoprotein E epsilon 2 allele is specific for patients with
cerebral amyloid angiopathy-related haemorrhage.
AB - The apolipoprotein E (APOE) epsilon 2 allele is a putative risk factor for
cerebral amyloid angiopathy-related haemorrhage. We explored the frequency of the
APOE epsilon 2 allele in intracranial haemorrhage due to three different
pathophysiological mechanisms to determine the specificity of the association.
APOE genotypes in 207 autopsies with intracranial haemorrhage (96 subarachnoid
haemorrhage, 71 deep intracerebral haemorrhage, 40 cerebral amyloid angiopathy
(CAA)-related haemorrhage patients) were compared with 41 autopsy controls
without neuropathological abnormalities and 406 living patients admitted to
hospital following head injury. As identified previously the epsilon 2 allele
frequency was significantly over-represented in CAA-related haemorrhage
(frequency 0.24, P < 0.01); this association was stronger among patients with
multiple CAA-related haematomas (0.31). The epsilon 2 frequencies of the deep
haemorrhage (0.13) and subarachnoid haemorrhage (0.09) groups were not
significantly different from the control autopsies (0.07) or live patients
(0.08). The findings indicate that the epsilon 2 allele is associated with
haemorrhage only in the context of cerebral blood vessels laden with amyloid.
PMID- 9637407
TI - Beta-actin immunoreactivity in rat microglial cells: developmental pattern and
participation in microglial reaction after kainate injury.
AB - In the present study we investigated the developmental and post-injury pattern of
beta-actin immunoreactivity in rat brain. Our data suggest that beta-actin is
higher in microglia-macrophages than in any other central nervous system cell
type, including neurons and astrocytes. We also show that beta-actin
immunoreactivity is particularly high in ameboid-macrophagic cells, suggesting a
role on the plastic changes that these cells experience during maturation or
after activation.
PMID- 9637408
TI - pH dependency of mu-calpain and m-calpain activity assayed by casein zymography
following traumatic brain injury in the rat.
AB - Studies employing casein zymographic assays analyzed the effects of varying pH
(from pH 6.8 to pH 8.0) on changes in mu-calpain and m-calpain activity in naive,
sham-injured and injured rat cortex 3 h following unilateral cortical impact
injury. Mu-calpain activity following cortical impact injury was enhanced between
pH values of 7.2 and 7.8, with pH 7.5 being optimal. m-Calpain activity was
readily detected only between pH values of 7.2 and 7.4, with pH 7.3 producing the
most prominent proteolytic activity. These observations suggest that strict
control of pH is an important consideration in assessments of brain pH activation
by casein zymography. Moreover, activation of different calpain isoforms,
especially after traumatic brain injury, may be differentially influenced by
smaller changes in physiological pH than previously recognized.
PMID- 9637409
TI - Expression of T lymphocyte adhesion molecules: regulation during antigen-induced
T cell activation and differentiation.
AB - The pattern of lymphocyte traffic and migration in vivo is a composite of
constitutive recirculation and transient changes induced by interaction with
antigen. Naive T lymphocytes in their basal, unstimulated state continuously
recirculate throughout the entire host, poised to react to specific antigens that
they are programmed to recognize. After interaction with antigen, T cell traffic
changes, first with the trapping of reactive cells in antigen-containing lymphoid
tissue. Subsequently, the effector cells responding to antigen, accompanied by
nonspecific T cells and monocytes, traffic in large numbers to sites of antigen
localization, resulting in the localized inflammatory response. Then, as the
immune response wanes, memory T cells develop, many of which exhibit still
different routes of recirculation. The traffic and tissue localization of
leukocytes is regulated by a series of cell surface adhesion molecules that
recognize specific ligands on endothelial cells and in the extracellular matrix.
Modulation of the expression of these adhesion molecules results in the changes
in T cell traffic that are characteristic of each stage of T cell
differentiation. Thus, during T cell activation and differentiation, the down
regulation of adhesion receptors specific for lymphoid tissue endothelium and up
regulation of integrins facilitate the targeting of effector cells to sites of
inflammation. Subsequent changes in adhesion receptors regulate the traffic of
the antigen-specific memory cells. T cell adhesion molecule expression is
therefore regulated as a function of the stage of activation and differentiation
and, in addition, is influenced by cytokines and the local lymphoid
microenvironment.
PMID- 9637410
TI - IL-2-induced cellular events.
AB - In this review we discuss several molecules that are attractive candidates as
transducing molecules involved in signaling processes. IL-2 receptor signaling is
a complex process involving a large number of molecules: Ras, Rho, PI3 kinase,
PKC, Akt, transcription factors NF-AT, and NF-kappaB and some target genes such
as bcl-2, c-myc, c-jun and c-fos. Ras and Rho have been defined as dual molecules
because Ras- and Rho-initiated signals can either promote or inhibit apoptosis.
Several studies have contributed to the delineation of a signaling pathway
structured in three independent channels designated channels 1, 2, and 3. These
three channels serve as major landmarks: Lck-c-fos/c-jun (channel 1), Syk-myc
(channel 2), and a pathway leading to actin organization/bcl-2 expression
(channel 3). The detailed hierarchical organization of these three channels is
presented throughout the review and the model is depicted in the figure.
PMID- 9637411
TI - Expression and function of recombination activating genes in mature B cells.
AB - Recombination activating genes, RAG-1 and RAG-2, encode proteins that catalyze
the rearrangement of immunoglobulin genes in B cells and T cell receptor genes in
T cells to generate the diversity of these important recognition molecules in
immune system. It has been believed that these gene rearrangements occur
exclusively in premature stages of B and T lymphocytes, consistent with the
observation that RAG expression is downregulated in mature lymphocytes. However,
recent studies have revealed that even mature B cells in peripheral lymphoid
tissues can reexpress RAG-1 and RAG-2 proteins following immunization.
Strikingly, RAG-expressing B cells are localized in the germinal centers (GCs) of
secondary lymphoid tissues in which somatic hypermutations, isotype switching,
and affinity maturation of antibodies take place. Recently, it has been shown
that RAG proteins thus induced are functional and can mediate the secondary
rearrangement of Ig genes (receptor editing) at mature stages of B cells.
Evidence is accumulating suggesting that GCs are regarded as a primary lymphoid
tissue. In the present review, we briefly summarize recent advances in the
expression and the characterization of RAG proteins and discuss their possible
role in mature B cells in relation to the diversification and the selection of B
cell repertoire in GCs.
PMID- 9637412
TI - Intraepithelial lymphocytes: origins, distribution, and function.
AB - Intraepithelial lymphocytes (IEL) are associated with the intestinal tract,
respiratory tract, genitourinary tract epithelium, and the skin and are the first
immune system cells to encounter pathogens that have invaded an epithelial
surface. IEL are predominantly T cells (CD3+) with CD8+ cells predominating at
most, but not all, sites. Both TCR alphabeta+ and TCR gammadelta+ cells are found
within IEL populations and an increasing body of evidence suggests that some IEL
may arise extrathymically. The presence within intestinal IEL of cells expressing
potentially self-reactive TCR suggests that T cell selection within epithelia may
differ from thymic T cell selection although recent evidence suggests that these
cells may in fact be nonresponsive. IEL exhibit various cytotoxic activities
including alloreactive and virus-specific CTL activity, NK activity and
spontaneous cytotoxicity, activities consistent with an immune surveillance or
first line of defence role. IEL also appear activated in vivo and secrete a
variety of cytokines. Subsets of IEL have been shown to provide B cell help, to
play a role in the maintenance of oral tolerance and to regulate epithelial cell
function. In this review the morphology, distribution and phenotype of IEL, the
potential for extrathymic development and possible functions of this unique
lymphoid population are discussed.
PMID- 9637413
TI - Proteases and cell-mediated cytotoxicity.
AB - Cytotoxic T lymphocytes and natural killer cells represent the body's primary
defense against viral-infected and tumorigenic cells. The classically described
mechanism by which these cells induce target cell death is granule mediated:
cytolytic granules within the killer cell are directionally exocytozed toward the
target cell, and the granule contents inflict a "lethal hit" on the target cell.
A second mechanism of cytotoxicity is now known to exist, and utilizes cell
surface receptors on the target cell, for which the ligand is expressed on the
killer cell. Receptor oligomerization results in the recruitment of cytoplasmic
proteins to the receptors and the transduction of a death signal to the target
cell. In both granule- and receptor-mediated cytotoxicity, the target cell dies
through a defined series of steps, which together are termed apoptosis. Recent
work on apoptosis has defined a family of cysteine proteases, the caspases, which
appear to be involved in the initiation of apoptosis in response to a number of
stimuli. This review focuses on studies that link these proteases to target cell
death induced by cytotoxic cells.
PMID- 9637414
TI - Some psychosocial aspects of nonlethal chondrodysplasias: I. Assessment using a
Life-Styles Questionnaire.
AB - Studies concerning the psychosocial aspects of skeletal dysplasias that cause
disproportionate short stature have been few and have usually involved small
numbers of patients. As part of a study involving patients with chondrodysplasias
and their families, an assessment battery of standardised instruments designed to
measure depression, anxiety, self-esteem, personal support networks, marital
adjustment, and family structure were completed by patients and, in many cases,
their sibs, spouses, and/or parents. This first in a series of six papers reports
the results of a Life-Styles Questionnaire which provides some insights into the
levels of satisfaction with various aspects of life, including friendships,
employment, the use of some substances and services, and the impact of the
skeletal dysplasia on career, marriage, and childbearing. Results are presented
for patients and the unaffected parents of patients. Overall, the study has shown
a high level of satisfaction with many aspects of life. However, there are
important differences in attitudes between the married and unmarried patients,
and in some cases the unaffected parents, in a number of areas including health,
overall satisfaction with life, and concerns surrounding child bearing and
employment.
PMID- 9637415
TI - Some psychosocial aspects of nonlethal chondrodysplasias: II. Depression and
anxiety.
AB - Individuals with chondrodysplasias may have disproportionate short stature and in
some cases a distinctive facial appearance. These physical signs have the
potential of affecting parent-child interactions and those of the dwarfed person
with broader society. Depression and anxiety are two psychological symptoms with
potential for a major impact on a person's functioning within society. In this
study depression and anxiety were assessed using the Beck Depression Inventories
and the Spielberger State-Trait Anxiety Inventories. While in general depression
did not appear more likely in dwarfs than in the general population, comparison
of adult patients with their unaffected sibs did raise some concern. Also, having
an unaffected parent or spouse appeared to be associated with higher depression
scores. Adult trait anxiety levels appeared higher, especially among women, than
normally expected in the general population and when compared with their
unaffected sibs.
PMID- 9637416
TI - Some psychosocial aspects of nonlethal chondrodysplasias: III. Self-esteem in
children and adults.
AB - Self-esteem is considered one of the most important personality attributes. It
correlates with physical and mental health and the ability to cope with stress.
The attitudes of others, and the experiences of interacting with them, are
considered as playing a major role in the development of self-esteem. Thus, those
patients with disproportionate short stature due to a chondrodysplasia can
reasonably be considered to be at risk of developing low self-esteem. In this
study, self-concept and self-esteem were measured in 159 children and adults with
various chondrodysplasias and disproportionate short stature. The results from
the children did not suggest that they had a lower concept of self than did their
unaffected sibs or a sample of average-size persons. By contrast, although the
adults did not differ significantly from a population sample, they scored
significantly below their unaffected sibs. There also appeared to be a trend to
lower scores among women, patients who had had an unaffected parent, and those
who were married to an unaffected spouse, although none of those differences were
statistically significant.
PMID- 9637417
TI - Some psychosocial aspects of nonlethal chondrodysplasias: IV. Dyadic scale of
marital adjustment.
AB - This article examines marital adjustment of couples who have had a child with
dwarfism due to a skeletal dysplasia, and of couples where one or both members
are dwarfs. The instrument used was the Dyadic Adjustment Scale developed by
Spanier [1976: Marriage Family 38:15-38]. The reasons for examining this
psychosocial aspect of dwarfism were that the birth of a dwarfed child to average
size parents might be expected to cause stress in the relationship, and because
several authors had raised concerns about the nature and/or quality of marriages
involving dwarfs. This study provides evidence of a decrease in the level of
marital adjustment for the average-size parents of affected children, gives
tentative reassurance about marriages where both individuals are dwarfs, but
raises some concerns about couples where only one member is a dwarf.
PMID- 9637418
TI - Some psychosocial aspects of nonlethal chondrodysplasias: V. Assessment of
personal social support using the Personal Resource Questionnaire.
AB - Social support has been shown to be an important influence on how an individual
copes with a number of stresses, including acute and chronic illness, psychiatric
morbidity, and life events. It can be thought of as a dynamic process consisting
of a network of persons who are available to provide support, and the level of
support that is perceived to be available from those persons. Patients with
disproportionate short stature due to a chondrodysplasia might be expected to
face greater challenges in developing a social support network. This study
assessed social support among a group of dwarfed patients using the Personal
Resource Questionnaire (PRQ85). The overall extent and functioning of social
support appears comparable to that in the general population, but there are some
differences when unmarried patients are compared with married patients and when
those who have affected spouses are compared with those whose spouses are of
average stature.
PMID- 9637419
TI - Some psychosocial aspects of nonlethal chondrodysplasias: VI. Assessment of
family interaction using the FACES II Questionnaire.
AB - Intrafamilial dynamics, including those between parents, and between parents and
their children, have an important influence on the ultimate success or failure of
a child's becoming a well adapted and socially integrated individual. Disability
and/or birth defects, such as dwarfism, may alter family functioning, either
because of the psychological impact or the day-to-day functional demands or both.
Family cohesiveness and adaptability and communication have been identified as
key variables that define how a family interacts. The Circumplex Model of Family
Systems defines the role of these factors in the family dynamic and the FACES II
scale provides a standardised assessment of their level of function within the
family. Thus families can be classified by their degree of cohesion,
adaptability, and the combination of the two. This article reports on the results
of the FACES II assessment that was completed by 107 patients with
disproportionate short stature due to a chondrodysplasia, as well as by a
variable number of their parents, sibs, or spouses.
PMID- 9637420
TI - Functional health status of adults with achondroplasia.
AB - Little is known regarding the functional health status of individuals with
achondroplasia. This cross-sectional survey of adults with achondroplasia was
undertaken to assess the functional health status of this population and its
determinants. The study sample consisted of members of the Little People of
America (LPA) who completed a mailed questionnaire consisting of a demographics
component, a general and disease-specific comorbidities component, and the Short
Form 36 (SF-36) health status questionnaire. Univariate analyses and multivariate
linear regression models were used for data analysis. Four hundred thirty-seven
individuals with a mean age of 38 years completed the survey. The age- and gender
adjusted Mental Component Summary (MCS) scores did not significantly differ from
those of the general population. In contrast, the age- and gender-adjusted
Physical Component Summary (PCS) scores were significantly lower than the general
population starting in the fourth decade of life. Musculoskeletal diseases were
most prevalent and had the greatest impact on the PCS scores. Two-thirds of this
cohort had undergone at least one operation. Only musculoskeletal procedures were
significantly associated with PCS and MCS scores. The functional health status of
adults with achondroplasia, as measured by the SF-36, is not drastically reduced
in comparison with that of the general U.S. population.
PMID- 9637421
TI - Clinical outcomes of four patients with microdeletion in the long arm of
chromosome 2.
AB - We present clinical outcome, through several years of follow-up, of 4 mentally
retarded patients, each with a small interstitial deletion in the long arm of
chromosome 2, within a region on which clinical reports are infrequent. Our
patient 1 was found to have del(2)(q22.3q23.3); patients 2 and 3,
del(2)(q23.3q24.2); and patient 4, del(2) (q24.2q31). By comparison of our cases
with each other and with those previously published with comparable interstitial
deletion, we attempted to identify characteristic clinical findings. Short neck
with excessive cervical skin was seen with monosomy of chromosome 2 bands q22.3
q23.3, while hypertrichosis and a peculiar high pitched cry were seen with
monosomy of chromosome 2 bands q23.3-q24.2. As suggested by Moller et al. [1984:
Hum Genet 68:77-86], a cleft between the first and second toes was seen with
monosomy of chromosome 2 bands q24.2-q31. In addition, seizure disorder was
present in patients 1 and 4 (with the more proximal and distal deletions,
respectively).
PMID- 9637422
TI - De novo apparently balanced complex chromosome rearrangement (CCR) involving
chromosomes 4, 18, and 21 in a girl with mental retardation: report and review.
AB - We describe a complex and unique, de novo apparently balanced translocation
involving chromosomes 4, 18, and 21 with 4 breakpoints, in a patient who was
referred for an evaluation of possible fragile-X syndrome. Fluorescence in situ
hybridization (FISH) confirmed the complexity of the rearrangement and showed the
derivative 21 to be composed of 3 distinct segments derived from chromosomes 21,
18, and 4. The derivative chromosome 18 had undergone a double translocation, the
first such event to be described in constitutional complex chromosomal
rearrangements (CCRs) involving chromosome 18. A review of these CCRs suggests
the existence of a breakpoint "hot spot" on 18q21.
PMID- 9637423
TI - 4q33-qter deletion and absorptive hypercalciuria: report of two unrelated girls.
AB - We report on two unrelated girls with multiple malformations, each of whom had a
der(4)t(4;?)(q33;?) chromosome--an unbalanced translocation chromosome with
deletion of the 4q33-qter segment and addition of a segment of an unknown
chromosome. One of the two girls had asymptomatic kidney stones. Both had excess
urinary calcium excretion (0.53 and 0.84 mg/mg creatinine, respectively),
exaggerated excretion on oral calcium load, and reduced but excessive excretion
on restricted calcium intake. The urinary calcium excretion of their parents was
normal. Both girls were thus diagnosed to have sporadic absorptive
hypercalciuria. It was deduced that the 4q33-qter segment contains the putative
gene for absorptive hypercalciuria.
PMID- 9637424
TI - Interstitial Dup(1p) with findings of Kabuki make-up syndrome.
AB - We describe a male patient with interstitial duplication of the short arm of
chromosome 1 with breakpoints involving 1p13.1 and 1p22.1. The patient presented
with some clinical findings of Kabuki make-up syndrome (KMS), including mental
retardation, small head, eversion of the lateral part of lower eyelids,
epicanthic folds, lateral flare of the eyebrows, short columella, and persistent
fetal finger pads. This cytogenetic finding may provide clues for gene mapping of
the syndrome.
PMID- 9637425
TI - Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B.
AB - We describe a diastrophic dysplasia (DTDST) gene mutation in a Japanese male
fetus with achondrogenesis type 1B and his relatives. Diagnosis in the fetus was
based on roentgenographic data and pathological findings of bones and cartilage.
Nucleotide sequencing of the DTDST gene demonstrated that the fetus was
homozygous for both delVal340 and Thr689Ser and his parents and a healthy brother
were heterozygous for the mutations. The former mutation was reported previously
in patients with achondrogenesis type 1B, and the latter was detected in 5
alleles of 26 healthy Japanese individuals. These data suggest that delVal340 is
associated with achondrogenesis type 1B in the Japanese, whereas a serine to
threonine substitution is most likely polymorphic.
PMID- 9637426
TI - A rare form of spondylometaphyseal dysplasia-type A4.
AB - We present 2 cases of a previously apparently unreported spondylo-metaphyseal
dysplasia comprising dwarfism, severe metaphyseal changes, ovoid vertebrae and
mild platyspondyly with anterior tonguing of the vertebral bodies. The
inheritance may be autosomal recessive.
PMID- 9637427
TI - Duplication of distal thumb phalanx in Shwachman-Diamond syndrome.
AB - Shwachman-Diamond syndrome (SDS) comprises of exocrine pancreatic dysfunction,
various degree of pancytopenia, and metaphyseal dysplasia. We report on a child
with SDS and duplication of distal thumb phalanx. This combination has not been
reported previously. We suggest that supernumerary thumb is likely a rare
skeletal manifestation of SDS and that SDS should be considered in the
differential diagnosis of patients with bone marrow failure and duplication of
the thumb along with Blackfan-Diamond/Aase syndrome and Fanconi's anemia.
PMID- 9637428
TI - New recessive syndrome characterized by increased chromosomal breakage and
several findings which overlap with Fanconi anemia.
AB - We describe four cases with several findings of Fanconi anemia (FA), but without
hypersensitivity to DNA cross-linking that is the distinguishing characteristic
of FA. Two of the cases are male and female sibs of Hispanic origin, age 6 years
and 11 months, respectively. Both have short stature, failure to thrive, absent
thumbs, short palpebral fissures, and skin pigmentation abnormalities. The girl
also has developmental "dysplasia" of her hips. Presently, both siblings are
hematologically normal. Elevated baseline chromosome breakage was observed in the
boy, but not in the girl. Neither sib showed elevated diepoxybutane (DEB)-induced
chromosomal breakage. In a subsequent pregnancy, prenatal studies showed slightly
elevated baseline and DEB induced chromosome breakage (greater than normal, but
lower than the established range for FA). The fetus had intrauterine growth
retardation and an absent right thumb. A review of cases referred to the
International Fanconi Anemia Registry for DEB testing showed one additional case
with similar findings. That patient, a girl, of Caucasian English ancestry, age
14 years, had short stature, a history of failure to thrive, skin pigmentation
abnormalities, absent right thumb, hypoplastic left thumb, and hydrocephalus that
resolved spontaneously. Elevated baseline chromosome breakage was observed in
skin fibroblasts but not in lymphocytes. We postulate that these cases represent
a previously undescribed autosomal recessive syndrome. These and other previously
reported cases provide evidence for alternative genetic mechanisms that may
result in developmental anomalies similar to those seen in FA.
PMID- 9637429
TI - Multiple schwannomas, multiple nevi, and multiple vaginal leiomyomas: a new
dominant syndrome.
AB - We report on a family of seven affected with a new syndrome of multiple deep
schwannomas, multiple nevi (both intradermal and compound types), and multiple
leiomyomas of the vagina. Inheritance is dominant, whether autosomal or X-linked
cannot be determined at this time. The nevi, which are congenital, appear to be a
marker for the syndrome. Both the schwannomas and leiomyomas do not manifest
until adulthood.
PMID- 9637430
TI - Delineation of the common critical region in Williams syndrome and clinical
correlation of growth, heart defects, ethnicity, and parental origin.
AB - Williams syndrome (WS) is a neurodevelopmental disorder with a variable
phenotype. Molecular genetic studies have indicated that hemizygosity at the
elastin locus (ELN) may account for the cardiac abnormalities seen in WS, but
that mental retardation and hypercalcemia are likely caused by other genes
flanking ELN. In this study, we defined the minimal critical deletion region in
63 patients using 10 microsatellite markers and 5 fluorescence in situ
hybridization (FISH) probes on chromosome 7q, flanking ELN. The haplotype
analyses showed the deleted cases to have deletions of consistent size, as did
the FISH analyses using genomic probes for the known ends of the commonly deleted
region defined by the satellite markers. In all informative cases deleted at ELN,
the deletion extends from D7S489U to D7S1870. The genetic distance between these
two markers is about 2 cM. Of the 51 informative patients with deletions, 29 were
maternal and 22 were paternal in origin. There was no evidence for effects on
stature by examining gender, ethnicity, cardiac status, or parental origin of the
deletion. Heteroduplex analysis for LIMK1, a candidate gene previously implicated
in the WS phenotype, did not show any mutations in our WS patients not deleted
for ELN. LIMK1 deletions were found in all elastin-deletion cases who had WS. One
case, who has isolated, supravalvular aortic stenosis and an elastin deletion,
was not deleted for LIMK1. It remains to be determined if haploinsufficiency of
LIMK1 is responsible in part for the WS phenotype or is simply deleted due to its
close proximity to the elastin locus.
PMID- 9637431
TI - Gaucher type 2 disease: identification of a novel transversion mutation in a
French-Irish patient.
PMID- 9637432
TI - Micro stent implantation in patients with acute myocardial infarction without
anticoagulation: clinical experience with two different antithrombotic protocols.
AB - The 4-week outcome following Micro stent implantation for acute myocardial
infarction was assessed with the use of two different antithrombotic regimens.
The patients were postprocedurally treated with acetyl salicylic acid (ASA) and
heparin for 24-48 h (Group I; n = 52), or ASA and ticlopidine plus abciximab if
indicated (Group II; n = 52). Stent implantation was successful in 49 patients
(94%) of group I and in 46 patients (89%) of group II (NS). Subacute stent
thrombosis occurred in nine patients (17%) of group I and in 1 patient (2%) of
group II (P < 0.05). There were no significant differences in the rates of
mortality, coronary bypass operation, or vascular complications. Micro stent
implantation in acute myocardial infarction is highly effective and associated
with a low risk for subacute stent thrombosis if the patients are
postprocedurally treated with ASA and ticlopidine plus abciximab if indicated.
PMID- 9637433
TI - Comparison of quantitative coronary angiographic results after directional
coronary atherectomy and balloon angioplasty of protected left main coronary
stenosis.
AB - We compared the angiographic and clinical outcomes after directional coronary
atherectomy (DCA, 13 patients) with those after conventional balloon angioplasty
(BA, 21 patients) in patients with protected left main coronary artery stenosis.
The initial success rate was 100% in the DCA group and 81% (17 of 21) in the BA
group. Restenosis was present in 2 of 11 patients in the DCA group and 9 of 16
patients in the BA group (18% vs. 56%, P < 0.05). DCA and BA improved a minimal
lumen diameter. The initial gain after DCA was greater than that after BA. At
follow-up, the minimal lumen diameter was larger and the percentage diameter
stenosis was smaller in the DCA group than in the BA group. The late loss and
loss index were equivalent in both groups. Compared with conventional BA, DCA in
protected left main coronary artery stenosis is associated with a higher
angiographic success rate and provides a wider luminal diameter with reduced
incidence of restenosis.
PMID- 9637434
TI - Percutaneous treatment of left main disease: keys to success.
PMID- 9637436
TI - Learning curve in the use of the radial artery as vascular access in the
performance of percutaneous transluminal coronary angioplasty.
AB - Radial artery access for coronary artery angioplasty is a cost-effective
alternative to other vascular entry sites. The initial series of patients using
the radial artery site for an operator without experience in using arm access for
coronary artery angioplasty was evaluated. Clinical success was achieved via the
radial artery in 87% of 32 lesions and 84% of 27 patients. The major feature
limiting success via the arm was radial/brachial artery spasm, which occurred in
30% of cases (clinical success: 50% with spasm vs. 95% without spasm, P < 0.05).
Spasm was more common in patients with peripheral vascular disease and in
hypertensive patients not treated with calcium channel blockers prior to
angioplasty. Coronary angioplasty via the radial artery may be successfully
performed even by the interventionalist inexperienced in arm access. Vascular
spasm is an important feature that limits the ability successfully to complete
coronary angioplasty via the radial artery.
PMID- 9637435
TI - Angioplasty of totally occluded old vein grafts with new interventional
techniques: a long-term follow-up study.
AB - The long-term patency of saphenous vein graft (SVG) lesions after intervention
has been shown to be improved with new interventional techniques such as stents.
Long-term outcome of patients undergoing successful angioplasty of totally
occluded old SVGs with new devices is unknown. From July 1994 to June 1996, 19
patients with totally occluded old SVGs had successful angioplasty with new
interventional techniques. Mean SVG age was 123 +/- 8 mo. Thrombolysis in
myocardial infarction trial (TIMI) flow was 0 in all target lesions. TIMI 2 or 3
flow was restored after angioplasty in all patients. Intracoronary urokinase,
transluminal extractional atherectomy, and stenting were used in 14, 12, and 6
patients, respectively. There was one in-hospital death due to ongoing myocardial
infarction, no recurrent infarction, and no repeat angioplasty or bypass surgery
in the hospital. At follow-up of 21 +/- 1 mo, there was one sudden death and one
myocardial infarction. Five patients had repeat coronary bypass surgery, and 4
had repeat angioplasty. Thirteen patients remained asymptomatic, and 4 had
angina. The long-term outcome of patients who had successful reopening of
occluded old SVGs is encouraging in this small sample.
PMID- 9637437
TI - Internal mammary artery graft angioplasty: acute and long-term outcome.
AB - Secondary to the low attrition rate of internal mammary artery grafts, limited
data are available on the clinical and angiographic outcome of patients who have
undergone balloon angioplasty of an internal mammary artery stenosis. This study
examined a consecutive series of 68 patients who underwent balloon angioplasty of
an internal mammary artery graft over a 9-year period. Procedural success was
achieved in 60 of 68 (88%) patients. The primary reason for procedural failure
was extreme vessel tortuosity. There were no major in-hospital complications.
Angiographic follow-up was obtained in 78% of the patients with an angiographic
restenosis rate of 19%. The overall event-free survival in patients with an
initially successful procedure was 92%. In conclusion, internal mammary artery
balloon angioplasty has both an excellent initial success rate as well as a low
incidence of restenosis and repeat target lesion revascularization.
PMID- 9637439
TI - Long stenting in native coronary arteries: relation between vessel size and
outcome.
AB - Procedural and 6-mo clinical outcomes were evaluated in 34 consecutive patients
who had stenting (<40 mm) of a long segment of coronary artery. Procedural
success was achieved in 32 (96%) patients. Before stenting, 32 (96%) patients had
Canadian Cardiovascular Society Class 3 or 4 angina compared to 7 (21%) at 6-mo
follow-up (P<0.001). Eleven patients (32%) suffered either acute/subacute stent
thrombosis (n=4) or restenosis (n=7). On logistic regression distal reference
diameter <2.5 mm (odds ratio 26, P<0.01) and previous cardiac intervention (odds
ratio 9.0, P<0.01) were independent predictors of a major adverse event during
follow-up. There was no significant association between outcome and indication
for stenting, type of stent, or use of ticlopidine and aspirin. These results
indicate that distal vessel diameter <2.5 mm is a powerful predictor of subacute
thrombosis or restenosis after long coronary artery stenting.
PMID- 9637438
TI - Comparison of thrombolytic therapy of lower-extremity acute, subacute, and
chronic arterial occlusions.
AB - Our purpose was to study the effectiveness of thrombolytic therapy in treating
acute, subacute, and chronic arterial occlusions in a multicenter retrospective
study. Intraarterial urokinase infusion was performed in 235 patients for
occluded native arteries. There were 70 (30%) with acute and 26 (5%) with
subacute occlusions, and 141 (59%) with chronic symptoms for longer than 3 mo.
Complete thrombolysis was achieved in 60 (86%) of the acute, 20 (77%) of the
subacute, and 106 (75%) of the chronic occlusions. Adjunctive interventional
procedures were performed as needed. Long-term follow-up revealed a primary
patency of 87%, 85%, and 76% for the acute, subacute, and chronic occlusion
groups, respectively. We conclude that the rate of complete thrombolysis of
chronic occlusions proved slightly more efficient for acute and virtually the
same for subacute occlusions. Long-term follow-up demonstrated a higher failure
rate with chronic than with acute occlusions, probably due to worsened peripheral
vascular runoff.
PMID- 9637440
TI - Summary of the Mayo Clinic experience with direct left ventricular puncture.
AB - Hemodynamic assessment of patients with prosthetic valves can be challenging.
Noninvasive techniques may be limited by interference from the prosthetic
material, whereas access to the left ventricle for direct pressure measurements
often is not possible using common methods. The technique of direct, percutaneous
left ventricular puncture has been proven to be a safe method that often provides
needed data to help manage difficult clinical situations. We report our 8-yr
experience with this technique for assessment of patients with valvular
prostheses. Direct left ventricular puncture is a safe technique in patients with
prior cardiac surgery and provided significant diagnostic information in the set
of patients with multiple valvular prostheses.
PMID- 9637441
TI - Evaluation of the compressive mechanical properties of endoluminal metal stents.
AB - The mechanical properties of metal stents are important parameters in the
consideration of stent design, matched to resist arterial recoil and vascular
spasm. The purpose of this study was to develop a system for a standardized
quantitative evaluation of the mechanical characteristics of various coronary
stents. Several types of stents were compressed by external hydrostatic pressure.
The stent diameter was assessed by placing a pair of small ultrasonic sono
crystals on the stent. From pressure-strain diagrams the ultimate strength and
radial stiffness for each stent were determined. For all stents, except the MICRO
II and the Wiktor stent, the diameter decreased homogeneously until an ultimate
compressive strength was exceeded, causing an abrupt collapse. Expanded to 3 mm,
the mechanical behavior of the beStent, the Crown and the Palmaz-Schatz stent
(PS153-series) were comparable. The spiral articulated Palmaz-Schatz stent showed
twice the strength (1.26 atm) of the PS-153 (0.65 atm). The NIR stent yielded a
maximum strength of 1.05 atm. The MICRO-II and the Wiktor stent did not collapse
abruptly but rather showed a continuous decline of diameter with increasing
external pressure. The Cardiocoil stent behaved in a fully elastic manner and
showed the largest radial stiffness. Difference in mechanical properties between
stents were documented using a new device specifically developed for that
purpose. These mechanical stent parameters may have important clinical
implications.
PMID- 9637442
TI - New indicator for stent covering area.
AB - A small gap between stent struts is essential to support the vessel wall, prevent
elastic recoil, and prevent intimal flaps from prolpasing into the lumen. We
defined Gap Index as the ratio of strut width divided by the percent of the
vessel wall area covered by the stent metal, and proved mathematically that this
index relates inversely to the total length of stent struts (or coil), and
directly related to stent cell size. Twenty-four (12 tubular and 12 coil) stents
from 17 manufacturers were analyzed. Strut width in the tubular and coil groups
was 354.1 +/- 276.0 and 955.9 +/- 553.9 microm, respectively (P < 0.001). The
relative metallic surface area (RMS) in the tubular and coil groups for 3 mm
stent diameter was 16.0 +/- 4.6 and 10.6 +/- 3.7%, respectively (P < 0.005).
Great variations in Gap Index were found amongst different stents, with up to 100
fold. Gap Index in the tubular and coil groups for 3 mm stent diameter was 24.4
+/- 21.7 and 105.8 +/- 97.5 units, respectively (P = 0.001). Thus, coil stents
have a smaller relative metallic surface area despite increased strut width. This
is the result of reduced total strut length and fewer and larger cells, as
represented by a higher Gap Index. This information may be useful for new stents
designs.
PMID- 9637443
TI - Progressive vascular remodeling and reduced neointimal formation after placement
of a thermoelastic self-expanding nitinol stent in an experimental model.
AB - Despite the improvements afforded by intracoronary stenting, restenosis remains a
significant problem. The optimal physical properties of a stent have not been
defined. We compared the vascular response to a thermoelastic self-expanding
nitinol stent with a balloon-expandable tubular slotted stainless steel stent in
normal porcine coronary arteries. Twenty-two stents (11 nitinol and 11 tubular
slotted) were implanted in 11 miniature swine. The nitinol stents were deployed
using the intrinsic thermal properties of the metal, without adjunctive balloon
dilation. The tubular slotted stents were implanted using a noncompliant balloon
with a mean inflation pressure of 12 atm. Intravascular ultrasound (IVUS) and
histology were used to evaluate the vascular response to the stents. The mean
cross-sectional area (CSA) of the nitinol stents (mm2) as measured by IVUS
increased from 8.13 +/- 1.09 at implant to 9.10 +/- 0.99 after 28 days (P =
0.038), while the mean CSA of the tubular slotted stents was unchanged (7.84 +/-
1.39 mm2 vs. 7.10 +/- 1.07 mm2, P = 0.25). On histology at 3 days, the tubular
slotted stents had more inflammatory cells adjacent to the stent wires (5.7 +/-
1.5 cells/0.1 mm2) than the nitinol (3.9 +/- 1.3 cells/0.1 mm2, P = 0.016). The
tubular slotted also had increased thrombus thickness (83 +/- 85 microm) than the
nitinol stents (43 +/- 25 microm, P = 0.0014). After 28 days, the vessel injury
score was similar for the nitinol (0.6 +/- 0.3) and the tubular slotted (0.5 +/-
0.1, P = 0.73) designs. The mean neointimal area (0.97 +/- 0.46 mm2 vs. 1.96 +/-
0.34 mm2, P = 0.002) and percent area stenosis (15 +/- 7 vs. 33 +/- 7, P = 0.003)
were significantly lower in the nitinol than in the tubular slotted stents,
respectively. We conclude that a thermoelastic nitinol stent exerts a more
favorable effect on vascular remodeling, with less neointimal formation, than a
balloon-expandable design. Progressive intrinsic stent expansion after implant
does not appear to stimulate neointimal formation and, therefore, may provide a
mechanical solution to prevent in-stent restenosis.
PMID- 9637444
TI - Successful coronary stenting in a 4-year-old child.
AB - This report describes a 4-yr-old with critical coronary artery stenosis acquired
after surgery for congenital heart disease. The patient was treated successfully
with coronary stenting after unsuccessful angioplasty.
PMID- 9637445
TI - Percutaneous transluminal coronary angioplasty in a 30-month-old child with
embolic long segment occlusion of the left anterior descending artery.
AB - A 30-mo-old girl developed occlusion of her left anterior descending coronary
artery following mitral valve replacement. She presented with refractory angina
pectoris. Successful percutaneous transluminal coronary angioplasty of the left
anterior descending artery was performed, resulting in restoration of flow,
resolution of anginal symptoms, and early improvement in left ventricular
function.
PMID- 9637446
TI - Coronary interventions in the pediatric patients: team (adult and pediatric)
approach.
PMID- 9637447
TI - Retrieval of "old" foreign bodies from the cardiovascular system in children.
AB - Several techniques have been developed to retrieve catheter and guide wire
fragments that have embolized to the heart and pulmonary vasculature. In most
instances, retrieval of the embolized fragments is performed soon after the event
has occurred. In this report, we summarize our experience with the removal of
these fragments in 3 children after a significant amount of time had elapsed
since the time of embolization. The embolized catheter and guide wire fragments
were removed without any complications. We also describe the techniques used for
their removal, and the problems encountered during the removal of these "old"
foreign bodies.
PMID- 9637448
TI - Vascular entrapment of a ruptured intra-aortic balloon: a case report of
successful removal without surgery.
AB - Intra-aortic balloon pump entrapment is a rare complication that may necessitate
major abdominal surgery that is potentially life threatening in the critically
ill patients who require balloon counterpulsation. We report successful removal
of a ruptured and entrapped intra-aortic balloon pump catheter after use of
streptokinase solution to clear clots from the device. We suggest this procedure
as a safer, nonsurgical method that may eliminate the need for abdominal surgery.
PMID- 9637449
TI - Fracture of coronary guidewire during rotational atherectomy with coronary
perforation and tamponade.
AB - We present the case of a calcified right coronary artery lesion with a 90-degree
exit angle. Attempts at rotational atherectomy led to wire transection and vessel
wall perforation necessitating emergent pericardiocentesis and bypass surgery. We
review the literature on complications of rotational atherectomy and the
management of coronary perforations and retained guidewire fragments.
PMID- 9637450
TI - Successful retrieval of a lost coronary stent from the descending aorta using a
loop basket intravascular retriever set.
AB - Delivery of a balloon-expandable stent was complicated by a systemic
embolisation. The radio-opaque stent was lost in the descending aorta, but then
removed by using a loop basket intravascular retriever set without any peripheral
arterial complication.
PMID- 9637451
TI - Hemodynamic rounds series II: pulmonic balloon valvuloplasty.
PMID- 9637452
TI - Laser wire for crossing chronic total occlusions: "learning phase" results from
the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser
Wire.
AB - The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO)
consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers
coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a
repetition rate ranging from 25-40 Hz. This laser guidewire was specifically
designed to cross total occlusions refractory to passage with conventional wires.
The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following
failure to cross a total occlusion with approved guidewires, the Prima wire was
utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations
included left anterior descending (36%), right (45%), and circumflex (19%)
coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2
1,020 wk, median, 14 wk). The use of the Prima wire either solely or in
combination with conventional guidewires resulted in successful crossing in 61%
of these previously impenetrable occlusions. Failure of the device was commonly
related to length of the occlusion and tortuosity along the occluded pathway.
Major complications included myocardial infarction in 7 patients (3.9%),
tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study
confirmed the feasibility of a laser guidewire in chronic total occlusions that
are resistant to passage of conventional guidewires. An extended registry at
these investigative sites is planned.
PMID- 9637453
TI - Novel guide catheter for left coronary intervention via a right upper limb
approach.
AB - We designed a novel guide catheter specifically for interventions to the left
coronary artery via a right upper limb approach. The catheter has a novel first
loop design which utilizes the angle between the right subclavian and innominate
arteries for support. The first loop introduces the catheter into the correct
position and generates powerful and coaxial back-up power. We report successful
implantation of Palmaz-Schatz stents in five cases using this 6 Fr. catheter.
PMID- 9637454
TI - Inoue balloon for dilatation of aortic stenosis.
PMID- 9637455
TI - Partial portacaval shunt for variceal hemorrhage: longitudinal analysis of
effectiveness.
AB - OBJECTIVE: To determine rates of survival, long-term patency, and recurrent
variceal hemorrhage among patients with alcoholic cirrhosis treated by partial
portacaval shunt. DESIGN: Single-institution cohort follow-up study of 72
consecutive patients who underwent small-diameter portacaval H-graft shunt with
collateral ablation during a 10-year period (1981 through 1990). Subjects were
enrolled and followed up for up to 15 years. Shunt patency was assessed by
portography and/or ultrasonography. We performed 7-year Kaplan-Meier analyses of
survival (in 65 patients in Child classes A and B), shunt patency, and absence of
variceal bleeding. SETTING: Tertiary academic referral center of the US
Department of Veterans Affairs. PATIENTS: Patients with alcoholic cirrhosis were
considered for operation after at least 1 proven episode of variceal hemorrhage.
Patients with portal vein thrombosis were excluded; patients in Child class C
underwent operation only for compelling indications. Of the 72 who underwent
partial shunting, 38 were in Child class A, 27 were in class B, and 7 were in
class C. INTERVENTIONS: Partial portacaval shunt (6-, 8- or 10-mm
polytetrafluoroethylene H-graft with collateral ablation) and serial follow-up.
MAIN OUTCOME MEASURES: Study end points were death, recurrent variceal
hemorrhage, and unavailability for follow-up. Other measures included graft
patency and nonvariceal rebleeding. RESULTS: Cumulative probability of 7-year
patency for grafts at risk was 95%. The 7-year probability for absence of
variceal bleeding in patients at risk was 92%. In 65 patients in Child classes A
and B, operative mortality was 7.7% and the cumulative probability of 7-year
survival was 54%. CONCLUSION: For variceal bleeding associated with alcoholic
cirrhosis, the small-diameter polytetrafluoroethylene portacaval H-graft with
collateral ablation affords durable patency and protection against variceal
rebleeding.
PMID- 9637456
TI - Transanal endoscopic microsurgery: a single surgeon's experience.
AB - OBJECTIVE: To evaluate a single surgeon's experience with transanal endoscopic
microsurgery (TEM) with regard to incidence of complications, recurrence rate of
benign and malignant lesions, and impact on the treatment of rectal cancer.
DESIGN: Prospective tumor registry. SETTING: Tertiary care university hospital.
PATIENTS: Seventy-three patients undergoing TEM between January 1991 and November
1996. MAIN OUTCOME MEASURES: Complications, recurrence rates, and use of this
technique with respect to radical operations. RESULTS: The arrival of TEM was
associated with an increase in the number of operations for rectal cancer;
however, the use of TEM remained constant relative to radical resections. Use of
TEM resection alone is appropriate for all adenomas and cancers staged Tis and
T1. Use of TEM alone is not an appropriate treatment for T2 cancers. Four
patients (5%) experienced fecal soilage, which was long lasting in only 1 (1%).
CONCLUSIONS: Transanal endoscopic microsurgery is a safe technique and provides
improved access to lesions in the middle and upper rectum. Thus far, it has not
had a significant impact in the overall treatment of rectal cancer.
PMID- 9637457
TI - An analysis of operations for gastroesophageal reflux disease: identifying the
important technical elements.
AB - BACKGROUND: Better understanding of the pathogenesis of gastroesophageal reflux
disease in recent years has not been accompanied by appreciable advances in the
design of antireflux operations. In many cases, operations are still being
performed just as they were described 30 years ago. It is important now to go
beyond the eponymous procedures traditionally associated with antireflux
operations and to identify the technical elements that contribute to effective
and durable fundoplications. OBJECTIVES: To compare antireflux operations and
identify the important technical elements. DESIGN AND SETTING: Retrospective
study in a university-based tertiary care center. PATIENTS: Two hundred one
patients had laparoscopic fundoplications for gastroesophageal reflux disease.
The first 22 patients underwent Nissen-Rossetti procedures (360 degree wrap; no
division of short gastric vessels). Subsequently, 82 patients had a total (360
degree Nissen wrap) fundoplication and 97 patients had a partial (240 degree
Guarner wrap) fundoplication (both with the short gastric vessels divided), with
the choice between them based on the quality of esophageal peristalsis. The 3
groups of patients were similar in age, duration of symptoms, incidence of hiatal
hernia, and incidence of esophagitis. MAIN OUTCOME MEASURES: Resolution of
heartburn, incidence of postoperative dysphagia, and stability of the
reconstruction. RESULTS: The resolution of heartburn was achieved for 15 patients
(68%) who had the Nissen-Rossetti procedure, 73 patients (89%) who had a 360
degrees Nissen wrap, and 88 patients (91%) who had a 240 degree Guarner wrap.
Postoperative dysphagia occurred in 3 patients (14%) having the Nissen-Rossetti
procedure, 5 patients (6%) having a 360 degree wrap, and 2 patients (2%) having a
240 degree wrap. Herniation or disruption of the wrap occurred postoperatively in
9 patients (4.5%). Review of the videotapes of these 9 operations showed that
important technical elements had been omitted in 8. Seven patients required a
second operation. CONCLUSION: Laparoscopic antireflux operations control symptoms
without producing adverse effects if the following technical elements are
included: the hernia is repaired and the hiatus reduced to a normal size, the
short gastric vessels are divided, a total or partial wrap is used based on the
quality of esophageal peristalsis, and the wrap is anchored in the abdomen.
PMID- 9637458
TI - Total mesenteric excision in the surgical treatment of rectal cancer: a
prospective study.
AB - BACKGROUND: Total mesorectal excision has been advocated in conjunction with low
anterior or abdominoperineal resection as the optimal surgical treatment for
rectal cancer. It involves removal of the entire rectal mesentery as an intact
unit and maximizes the likelihood of obtaining a negative circumferential margin.
OBJECTIVES: To prospectively validate the efficacy of total mesorectal excision
in obtaining locoregional control, to identify the perioperative factors
influencing the selection of either a sphincter sparing or a sphincter ablating
procedure, and to identify independent factors that may influence long-term
prognosis in rectal cancers. SETTINGS: Tertiary referral center. PATIENTS:
Seventy-three consecutive patients with rectal cancer located within 10 cm of the
anal verge were treated from 1984 to 1997 by the senior author (F.M.). Sixty-five
patients form the basis of our analysis after the exclusion of 7 patients who had
their cancer removed transanally and 1 patient who had a permanent diverting
stoma as the only procedure. RESULTS: Twenty-six patients underwent a sphincter
ablating procedure; 39 underwent a sphincter sparing procedure. Operative
mortality was 1.5%. Follow-up was complete in 64 patients (39+/-30 months; range,
3-126 months). Five-year actuarial survival rates were 88% for the 34 patients
with stage I and II adenocarcinoma and 65% for the 22 patients with stage III
adenocarcinoma. The local recurrence rate was 6.2% overall, but only 3.1% in the
potentially curable group (stages I-III). When only patients who did not receive
adjuvant chemoradiation therapy were considered (n=23), local recurrence rate was
8.3% overall and 0% in the potentially curable group. Tumor stage (P=.04) and
vascular and/or lymphatic invasion (P=.002) were statistically significant in
their association with survival. Circumferential lesions (P<.001), gross invasion
of contiguous organs (P<.001) and distance from the anal verge of less than 5 cm
(P=.01) were statistically significant in their association with the choice of a
sphincter ablating procedure. CONCLUSIONS: This study confirms the efficacy of
total mesorectal excision in minimizing locoregional recurrence rates and
confirms the well-established prognostic value of stage and microinvasion.
Moreover, it indicates that circumferential lesions, distance from anal verge,
and gross invasion of contiguous organs are significant perioperative factors in
the selection of the type of surgical procedure.
PMID- 9637459
TI - Assessing outcomes, costs, and benefits of emerging technology for minimally
invasive saphenous vein in situ distal arterial bypasses.
AB - BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ
peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion
has recently been approved for use. Despite the attractiveness of this approach
(2 short incisions), benefits such as lower morbidity and shorter
hospitalizations remain undocumented. To justify wide acceptance, minimally
invasive surgical techniques must match conventional procedures in durability and
cost while enhancing patient comfort. Often such comparisons are difficult during
the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes
of the MIAB procedures with a concurrent group of patients undergoing
conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING:
University medical center. PATIENT: The first 20 consecutive MIAB procedures in
19 patients performed between August 1, 1995, and July 31, 1997, were compared
with 19 contemporaneous consecutive conventional in situ bypass procedures
performed at the same institution. MAIN OUTCOME MEASURES: Operative time,
postoperative length of stay, hospital costs, complications, primary assisted and
secondary patency, limb salvage, and survival. RESULTS: The patient groups were
comparable with respect to age, sex, incidence of smoking, coronary artery
disease, hypertension, diabetes, renal failure, cerebrovascular disease,
indication, and distal anastomosis level. The median operative time was
significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and
intraoperative completion arteriography more frequently showed retained
arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median
postoperative length of stay and total cost were 6.5 days and $18,000 for the
MIAB group and 8 days and $27,800 for the conventional group (P > or = .05).
There were no significant differences in major complications (10% in the MIAB
group vs 11% in the conventional group), wound complications (10% vs 11%,
respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%,
respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively),
limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival
at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing
the MIAB procedure avoided lengthy vein exposure incisions without sacrificing
short-term results. There was a trend toward decreased hospital stay and cost,
which may be further realized as the clinical experience broadens. Although
longer follow-up and larger cohorts will always be required to define durability,
immediate access to outcomes and costs on small numbers of patients facilitates
the early assessment of emerging technology.
PMID- 9637460
TI - Delayed complications of nonoperative management of blunt adult splenic trauma.
AB - OBJECTIVE: To determine the incidence and type of delayed complications from
nonoperative management of adult splenic injury. DESIGN: Retrospective medical
record review. SETTING: University teaching hospital, level I trauma center.
PATIENTS: Two hundred eighty patients were admitted to the adult trauma service
with blunt splenic injury during a 4-year period. Men constituted 66% of the
population. The mean (+/-SEM) age was 32.2+/-1.0 years and the mean (+/-SEM)
Injury Severity Score was 22.8+/-0.9. Fifty-nine patients (21%) died of multiple
injuries within 48 hours and were eliminated from the study. One hundred thirty
four patients (48%) were treated operatively within the first 48 hours after
injury and 87 patients (31%) were managed nonoperatively. MAIN OUTCOME MEASURES:
We reviewed the number of units of blood transfused, intensive care unit length
of stay, overall length of stay, outcome, and complications occurring more than
48 hours after injury directly attributable to the splenic injury. RESULTS:
Patients managed nonoperatively had a significantly lower Injury Severity Score
(P<.05) than patients treated operatively. Length of stay was significantly
decreased in both the number of intensive care unit days as well as total length
of stay (P<.05). The number of units of blood transfused was also significantly
decreased in patients managed nonoperatively (P<.05). Seven patients (8%) managed
nonoperatively developed delayed complications requiring intervention. Five
patients had overt bleeding that occurred at 4 days (3 patients), 6 days (1
patient), and 8 days (1 patient) after injury. Three patients underwent
splenectomy, 1 had a splenic artery pseudoaneurysm embolization, and 1 had 2
areas of bleeding embolization. Two patients developed splenic abscesses at
approximately 1 month after injury; both were treated by splenectomy. CONCLUSION:
Significant numbers of delayed splenic complications do occur with nonoperative
management of splenic injuries and are potentially life-threatening.
PMID- 9637461
TI - CD4 cell counts as a prognostic factor of major abdominal surgery in patients
infected with the human immunodeficiency virus.
AB - OBJECTIVE: To measure the prognostic utility of helper T-cell (CD4) counts in
human immunodeficiency virus (HIV)-infected patients undergoing major abdominal
surgery. DESIGN: Retrospective case series. SETTING: Three university-affiliated
hospitals. PATIENTS: Forty-three HIV-infected patients undergoing major abdominal
surgery. MAIN OUTCOME MEASURES: Morbidity and mortality rates with respect to CD4
cell counts. RESULTS: Nineteen of 32 patients who had CD4 cell counts less than
0.20 X 10(9)/L (200 cells/microL) suffered major complications compared with 2 of
11 patients who had CD4 cell counts greater than 0.20 x 10(9)/L (200
cells/microL) (P=.03). Perioperative mortality was 38% for patients with CD4 cell
counts less than 0.20 x 10(9)/L, and was 9% for those with CD4 cell counts
greater than 0.20 x 10(9)/L (P=.13). Six months postoperatively, mortality rates
were 47% and 9%, respectively (P=.03). Of patients with septic processes
perioperatively (n=12), mortality was 75%, and was 19% (P=.009) for those with
nonseptic processes (n=31). Nine patients had HIV-related intra-abdominal
pathologic conditions at laparotomy. Mortality was 56% perioperatively (P=.13)
and 88% after 6 months (P=.001). Sixty-eight percent of patients who received
blood product transfusions developed complications, whereas only 7% of those who
did not receive transfusions developed complications (P<.001). Overall mortality
and morbidity rates were 37% and 49%, respectively. Patients with morbidity had
lower CD4 cell counts (median, 0.034 x 10(9)/L) than those without complications
(median, 0.102 x 10(9)/L) (P=.02). Similarly, patients who died had lower CD4
cell counts (median, 0.031 x 10(9)/L vs 0.088 x 10(9)/L) (P=.05). CONCLUSIONS:
Patients with acquired immunodeficiency syndrome-defining CD4 cell counts
undergoing major abdominal surgery developed more complications and had poorer
outcomes at 6-month follow-up compared with HIV-infected patients whose CD4 cell
counts were greater than 0.20 x 10(9)/L (200 cells/microL). A perioperative
septic process and HIV-related pathologic conditions seen at laparotomy are also
associated with worse outcomes.
PMID- 9637462
TI - Intra-aortic balloon counterpulsation in patients with severe cardiac dysfunction
undergoing abdominal operations.
AB - OBJECTIVE: To assess the effectiveness of intra-aortic balloon counterpulsation
(IABC) as adjunctive treatment in patients undergoing abdominal operations.
DESIGN: Retrospective review of patient medical records to determine the
incidence of mortality following abdominal surgery and the incidence of
complications from IABC. SETTING: University-based, tertiary care hospital.
PATIENTS: Sixty-eight patients who underwent an abdominal operation and IABC
during the same hospitalization were divided into the following groups: Group 1,
IABC initiated prior to operation to enhance perioperative cardiac function;
group 2, IABC used to treat cardiogenic shock in a patient who subsequently
required an operation while undergoing IABC; and group 3, IABC device inserted
and removed for treatment of cardiogenic shock in a patient who subsequently
required an operation within 30 days of removal of the device. MAIN OUTCOME
MEASURES: The incidence of mortality in IABC-supported patients and IABC-related
complications. RESULTS: In group 1, excluding 3 patients who died following
emergency operation, 26 patients underwent nonemergency procedures and had a 12%
mortality rate. In group 2, 5 of 6 patients who underwent emergency operations
died, whereas 3 of 4 patients who required only urgent operations survived. In
group 3, 18 (62%) of 29 patients who underwent urgent or emergent operations died
postoperatively. Thirteen patients experienced complications related to IABC;
there were no deaths and no limbs were lost to ischemia. CONCLUSIONS: This is the
largest reported series looking at the utility of IABC as adjunctive treatment
for patients undergoing abdominal operations. The outcome for those patients
requiring emergency operations remains poor, but it is likely that more liberal
use of IABC in patients with severe cardiac dysfunction who require nonemergency
operations may improve patient outcome.
PMID- 9637464
TI - Treatment strategy for patients with cystic lesions mimicking a liver tumor: a
recent 10-year surgical experience in Japan.
AB - OBJECTIVE: To clarify some of the difficulties in determining the appropriate
surgical indications for cystic lesions mimicking a neoplasm in the liver.
DESIGN: A retrospective review of hepatic resections for cystic lesions mimicking
a neoplasm in the liver between August 1, 1986, and July 31, 1996. SETTING: A
university hospital with a long history of hepatic resection for cystic lesions
mimicking a neoplasm in the liver. PATIENTS: Ten patients with such cystic
lesions in the liver, who underwent a hepatectomy during a recent 10-year period,
were included in this study. MAIN OUTCOME MEASURES: Detailed clinicopathologic
data were analyzed, and comparisons were made between the preoperative and
postoperative diagnoses. RESULTS: The postoperative diagnoses consisted of cysts,
including cysts complicated by an infection or hemorrhage in 7 patients,
localized cystic dilation of the bile duct due to hepatolithiasis in 1,
cystadenoma in 1, and mucin-producing cholangiocarcinoma in 1. In only one case
was postoperative diagnosis identical to the preoperative diagnosis. In one case,
an intraoperative pathological examination showed the tumor to be a mucin
producing cholangiocarcinoma instead of a cystadenocarcinoma. A tumor-marker
analysis of the fluid in the cystic lesions also did not contribute to a definite
diagnosis. Furthermore, cytological examination of the fluid could not completely
exclude malignancy. Neither mortality nor morbidity occurred in any of the
patients, and their mean length of hospitalization after hepatectomy was only
13.7 days. CONCLUSIONS: The accurate diagnosis of cystic lesions mimicking a
tumor remains problematic; however, the results of hepatectomy for such cases are
normally satisfactory. Such cystic lesions of the liver should be indicated for
hepatectomy whenever the possibility of a cancerous neoplasm cannot be completely
ruled out.
PMID- 9637463
TI - Video-assisted thoracic surgery in the treatment of posttraumatic empyema.
AB - BACKGROUND: Video-assisted thoracic surgery (VATS) appears to be replacing open
thoracotomy for the treatment of posttraumatic thoracic complications. OBJECTIVE:
To compare operative times, complication rates, and outcomes in patients who
underwent VATS vs open thoracotomy. DESIGN: Retrospective review. SETTING:
University hospital, level I trauma center. PATIENTS: Trauma patients who between
December 1993 and May 1997 underwent open thoracotomy or VATS to drain a
persistent thoracic collection. METHODS: Medical records were reviewed for
demographic data, operative times, and clinical outcomes. RESULTS: Of the 524
trauma patients requiring tube thoracostomy, 22 underwent 23 procedures to drain
empyema (17 VATS, 6 thoracotomies [based on surgeon preferencel). There were no
differences in age, Injury Severity Score, or mechanism of injury between the 2
groups. Three patients who underwent VATS (18%) required conversion to open
thoracotomy for adequate drainage. All remaining patients who underwent VATS had
successful treatment of their empyema. Complication rates (VATS=29%, open
thoracotomy=33%; P=.99), operative times (VATS=3.4+/-1.3 hours [mean+/-SD], open
thoracotomy=3.0+/-1.5 hours; P=.46), postoperative epidural catheter use
(VATS=31%, open thoracotomy=50%; P=.63), duration of chest tube drainage
(VATS=5.1+/-1.7 days [mean+/-SD], open thoracotomy=4.5+/-1.5 days; P=.48), and
hospital stay after the procedure (VATS=16+/-14 days [mean+/-SD], open
thoracotomy=11+/-5 days; P=.39) were similar for both groups. CONCLUSIONS: Video
assisted thoracic surgery was a safe and effective operative strategy for the
treatment of posttraumatic empyema. Therefore, because VATS has been shown in
nontrauma patients to reduce morbidity and because it provides better cosmesis,
we believe that it should be the initial operative approach to trauma patients
with suspected posttraumatic empyema.
PMID- 9637465
TI - Therapeutic effect of sentinel lymphadenectomy in T1 breast cancer.
AB - OBJECTIVE: To evaluate whether the tumor status of the sentinel lymph node (SN)
would alter the systemic adjuvant therapy administered to patients with T1 breast
cancer. DESIGN AND PATIENTS: Consecutive breast cancer patients (tumors < or = 2
cm) who underwent successful sentinel lymphadenectomy. MAIN OUTCOME MEASURES:
Metastatic tumor in the SN, primary tumor size, recommendations for systemic
adjuvant therapy before and after histopathologic evaluation of the SN, and
actual systemic adjuvant therapy received by the patient. RESULTS: Of 142 total
patients, 14 had T1a tumors; 35, T1b; and 93, T1c. Recommendations for systemic
adjuvant therapy were initially determined solely by primary tumor
characteristics and menopausal status. These recommendations were compared with
recommendations for systemic adjuvant therapy based on tumor characteristics,
menopausal status, and SN status; and then were compared with actual systemic
adjuvant therapy received by the patient. Among the 118 patients with T1a, T1b,
and favorable (positive estrogen or progesterone receptors and a low S-phase
percentage with respect to DNA content) T1c tumors, 15 (37.5%) of 40
premenopausal patients and 20 (25.6%) of 78 postmenopausal patients became
candidates for chemotherapy when examination of the SN revealed axillary
metastasis; chemotherapy was actually administered to all 15 premenopausal
patients but to only 6 postmenopausal patients. In the remaining 24 patients with
unfavorable T1c tumors, SN status did not change the recommendation for
chemotherapy but may have altered the choice of specific chemotherapeutic agents.
CONCLUSIONS: Identification of tumor-involved SN may alter systemic adjuvant
therapy in patients with T1a, T1b, and favorable T1c tumors and may potentially
change the type or dose of chemotherapeutic agents given to patients with
unfavorable T1c tumors. Surgical axillary staging of the axilla remains an
essential part of breast cancer management and should not be abandoned.
PMID- 9637466
TI - Effects of carbon dioxide pneumoperitoneum, air pneumoperitoneum, and gasless
laparoscopy on body weight and tumor growth.
AB - BACKGROUND: The oncologic consequences of intraperitoneal carbon dioxide (CO2)
insufflation during the laparoscopic resection of cancer are under debate. The
effect of other insufflating gases or gasless laparoscopy on cancer requires
study. OBJECTIVE: To study body weight and tumor growth in rats after CO2
pneumoperitoneum, air pneumoperitoneum, and gasless laparoscopy. METHODS: On day
1, an 8-mg bolus of ROS-1 tumor was placed under the renal capsule of both
kidneys in rats. In experiment A, rats had either CO2 insufflation (n=10) or a
gasless laparoscopic bowel resection (n=10) on day 3 and were humanely killed
after 7 days. In experiment B, rats had either a laparoscopic bowel resection
with CO2 insufflation (n=11) or insufflation with air (n=11) on day 3 and were
killed after 7 days. In both experiments, postoperative weight loss and tumor
growth were measured, and the differences were tested with an analysis of
covariance. RESULTS: Renal subcapsular tumor growth in the group having gasless
laparoscopy was less than that in the group having CO2 pneumoperitoneum (P=.04).
Postoperative weight loss in these groups showed no differences (P=.55). No
differences in tumor growth or weight loss were found between rats having
insufflation with CO2 and those having insufflation with air (P=.61 and P=.68,
respectively). CONCLUSIONS: The restoration of body weight after a laparoscopic
surgical procedure was similar with CO2, air, or gasless laparoscopy. Gasless
laparoscopy was associated with less renal subcapsular tumor growth than was
insufflation with CO2. Therefore, the application of gasless techniques in
laparoscopic oncologic surgical treatment demands further study.
PMID- 9637467
TI - Objective evaluation of a laparoscopic surgical skill program for residents and
senior surgeons.
AB - BACKGROUND: Laparoscopic surgery adapts poorly to apprenticeship models for
general surgical training. Standardized skill acquisition and validation
programs, targeted performance goals, and a supervised, enforced, skill-based
curriculum that readily can be shared between trainee and instructor must replace
the observation and incremental skill-acquisition model used in an open surgical
environment. The Yale Laparoscopic Skills and Suturing Program was used to
develop a data bank for objective evaluation of dexterity and suturing skills for
laparoscopic surgical training. The current study compares trainee and senior
surgeon performance in this standardized training program. OBJECTIVE: To compare
objectively evaluated laparoscopic surgical skills and suturing capability of
senior surgeons and of residents after they have completed the same standardized
training regimen. METHODS: Two hundred ninety-one trained surgeons performed 8730
standardized laparoscopic dexterity drills and 2910 intracorporeal suturing
exercises in the Yale Laparoscopic Skills and Suturing Program. Their performance
was supervised by an instructor who recorded performance and timing of the tasks
in a 2 1/2-day program. Ninety-nine residents performed the same drills and
exercises the same number of times and followed the same technique for
intracorporeal suturing. Percentile graphs were prepared for each type of drill
and suturing exercise to allow comparison of levels of achievement among
different training groups. RESULTS: The performance of the residents was the same
as that of trained surgeons for the rope pass drill and the suturing exercise.
Residents in comparison with trained surgeons performed the triangle transfer
drill faster and the new cup drop drill and old cup drop drill more slowly. There
was no significant difference in performance between male and female residents.
CONCLUSION: Basic skills relevant to laparoscopic performance can be acquired
with a high level of competence in a brief course unrelated to prior surgical
experience, sex, or age.
PMID- 9637468
TI - Diagnostic delay in breast disease: a system analysis of a public urban hospital.
AB - OBJECTIVE: To analyze the diagnostic process in 146 women referred to a breast
clinic in an urban setting between January 1, 1994, and December 31, 1996.
DESIGN: We devised the "diagnostic delay index (DDI)," defined as the time
between the medical system's awareness of a diagnostic need and the completion of
the diagnostic process. The time awaiting breast clinic consultation and the
diagnostic events experienced--including clinic visits, imaging studies, and
biopsies--were recorded. We stratified patients in 2 pathways (palpable masses
and mammogram-identified lesions) and by benign or malignant outcome. RESULTS:
Patients in pathways 1 (n = 85) and 2 (n=61) had a mean (+/-SD) DDI of 68.4 (+/
46.9) days and 71.9 (+/-35.2) days, respectively. Patients in both pathways who
had a malignant outcome had a significantly lower DDI than those who had a benign
outcome (47.5+/-30.9 days vs 78.6+/-42.6) (P<.001); this advantage was most
pronounced in patients with palpable lumps. The average patient waited more than
3 weeks for both an initial clinic consultation and operating room access.
Quartile analysis of the DDI revealed statistically significant differences in
clinic access time, number of visits, diagnostic events per visit, and operating
room access time. Regression analysis demonstrates the relationship between DDI
and measured process variables: DDI= -21.11+0.09 age+1.86 pathway-12.18
outcome+1.08 clinic access+11.91 visits+0.94 operating room access (R2=61.5%).
CONCLUSIONS: In a public hospital, diagnostic delay is related to inadequate
access to surgical consultation and a delay in operating room access. Regression
analysis demonstrates the relationships between these components of system
diagnostic delay and suggests strategies for reducing the DDI.
PMID- 9637470
TI - Spigelian hernias: a new repair technique using preshaped polypropylene umbrella
plugs.
AB - The spigelian hernia is a rare kind of abdominal wall defect that has been
treated using a variety of techniques. Recently, we encountered 6 patients with
spigelian hernias in whom we have used a new modality consisting of the tension
free occlusion of the hernia ring with a preshaped polypropylene umbrella-type
plug. The follow-up was more than 1 year without evidence of recurrence. This
technique simplifies the repair and has the advantage of producing minimal
postoperative pain and disability.
PMID- 9637469
TI - Genes don't count.
AB - It is the regulation of gene expression that determines phenotype and cellular
response. Several families of proteins control gene expression in cells and
influence the pathogenesis of multiple organ failure, the acute phase response,
atherosclerosis, and graft-vs-host disease. Understanding the basics of the
regulation of gene transcription will allow the knowledgeable surgeon to target
gene expression as a therapeutic modality in multiple diseases. We examine
nuclear factor kappa B as an example of a transcription factor that is involved
in multiple surgical diseases and has pharmacological inhibitors available to
knowledgeable surgeons.
PMID- 9637471
TI - Osteitis fibrosa cystica with renal parathyroid hormone resistance: a review of
pseudohypoparathyroidism with insight into calcium homeostasis.
AB - Pseudohypoparathyroidism is a group of diseases characterized by renal resistance
to parathyroid hormone. The patients typically have the bony manifestations of
hyperparathyroidism, while being hypocalcemic. Pseudohypoparathyroidism has
further been subdivided into types Ia, Ib, Ic, and II. Mutations involving any
number of domains of the parathyroid hormone receptor, adenylate cyclase, or G
proteins may alter the cellular response to parathyroid hormone. This wide range
of possible sites of mutation may explain the heterogeneous biochemical,
skeletal, and physical phenotypes associated with the various types of
pseudohypoparathyroidism. We describe a patient with pseudohypoparathyroidism who
was successfully treated with total parathyroidectomy and gland
autotransplantation. The complexities of parathyroid hormone cellular
interactions and calcium homeostasis are discussed. Pseudohypoparathroidism is an
unusual disease; however, it provides an elegant model for studying problems of
calcium balance.
PMID- 9637472
TI - RET proto-oncogene mutation analysis for multiple endocrine neoplasia, type 2.
PMID- 9637473
TI - Problems of total parenteral nutrition.
PMID- 9637474
TI - When giants walked the land.
PMID- 9637475
TI - Eiloides of the neck in a negro girl.
PMID- 9637476
TI - Cutting edge: role of macrophage migration inhibitory factor in inhibiting NK
cell activity and preserving immune privilege.
AB - The absence of MHC class I Ags on the corneal endothelium, which lines the
anterior chamber of the eye, makes this cell layer potentially vulnerable to
lysis by NK cells. However, aqueous humor (AH), which bathes the corneal
endothelium, contains a 12-kDa protein which inhibits the NK-mediated lysis of
corneal endothelial cells. An amino acid sequence analysis of AH revealed that
this factor shared >90% homology with macrophage migration inhibitory factor
(MIF). The NK inhibitory effect of AH was neutralized with anti-human MIF Ab.
Moreover, mouse rMIF produced a similar inhibition of NK cell activity. However,
neither rMIF nor AH inhibited the CTL-mediated Lysis of allogeneic cells. rMIF
prevented the release of perforin granules by NK cells but not CTLs. Although MIF
displays proinflammatory properties, these results indicate that it can also
inhibit at least one immune effector element, NK cells, and thereby contribute to
immune privilege in the eye.
PMID- 9637477
TI - Cutting edge: JAK3 activation and rescue of T cells from HIV gp120-induced
unresponsiveness.
AB - In early HIV disease, immunodeficiency is characterized by the inability of CD4+
T cells to produce a critical cytokine, IL-2, and to express the receptor for IL
2 (IL-2R) in response to antigenic or mitogenic stimulation. The shared common
gamma-chain (gamma(c)) of IL-2R and its associated Janus kinase, JAK3, are
indispensable for normal T cell function. Here, we show that the inhibition of IL
2R expression and proliferation induced by ligation of CD4 by HIV envelope
glycoprotein, gp120, is correlated with inhibition of expression and activation
of JAK3. Stimulation through the gamma(c)-related cytokine receptors restores
JAK3 expression and activation and rescues CD4-mediated T cell unresponsiveness.
Collectively, these data argue that inhibition of JAK3 expression and activation
may, in part, explain the T cell dysfunction seen in early HIV disease. In
addition, rescue from gp120-mediated T cell unresponsiveness by activation of
JAK3 suggests a novel therapeutic approach for enhancing immune function in HIV
disease.
PMID- 9637478
TI - Cutting edge: antigen-dependent regulation of telomerase activity in murine T
cells.
AB - Telomeres, structures on the ends of linear chromosomes, function to maintain
chromosomal integrity. Telomere shortening occurs with cell division and provides
a mechanism for limiting the replicative potential of normal human somatic cells.
Telomerase, a ribonucleoprotein enzyme, synthesizes telomeric repeats on
chromosomal termini, potentially extending the capacity for cell division. The
present study demonstrates that resting T cells express little/no activity, and
optimal Ag-specific induction of telomerase activity in vitro requires both TCR
and CD28-B7 costimulatory signals. Regulation of telomerase in T cells during in
vivo Ag-dependent activation was also assessed by adoptive transfer of TCR
transgenic T cells and subsequent Ag challenge. Under these conditions,
telomerase was induced in transgenic T cells coincident with a phase of extensive
clonal expansion. These findings suggest that telomerase may represent an
adoptive response that functions to preserve replicative potential in Ag-reactive
lymphocytes.
PMID- 9637479
TI - Specific immune induction following DNA-based immunization through in vivo
transfection and activation of macrophages/antigen-presenting cells.
AB - The initiation of an adaptive immune response requires Ag presentation in
combination with the appropriate activation signals. Classically, Ag presentation
and immune activation occur in the lymph node and spleen, where a favorable organ
architecture and rich cellular help can enhance the process. Recently, several
investigators have reported the use of DNA expression cassettes to elicit
cellular and humoral immunity against diverse pathogens. Although the immune
mechanisms involved are still poorly understood, plasmid inoculation represents a
model system for studying immune function in response to invading pathogens. In
this report, we demonstrate the presence of activated macrophages or dendritic
cells in the blood lymphocyte pool and peripheral tissues of animals inoculated
with DNA expression cassettes. These cells are directly transfected in vivo,
present Ag, and display the surface proteins CD80 and CD86. Our studies indicate
that these cells function as APC and can activate naive T lymphocytes. They may
represent an important first step APC in genetic immunization and natural
infection.
PMID- 9637480
TI - Factors involved in the differentiation of TGF-beta-producing cells from naive
CD4+ T cells: IL-4 and IFN-gamma have opposing effects, while TGF-beta positively
regulates its own production.
AB - TGF-beta has been shown to play a central role in regulating inflammatory
responses; thus, understanding the factors involved in the generation of TGF-beta
producing cells could lead to interventions that are useful in effecting disease
progression. In initial studies, the capacity of naive CD4+ T cells from TCR
transgenic (Tg) mice to produce TGF-beta following primary and secondary
stimulation was assessed. TGF-beta, IL-4, or IFN-gamma production could not be
detected from highly purified naive CD4+/lymphocyte endothelial cell adhesion
molecule (LECAM)-1high cells following primary stimulation for 36 h with plate
bound anti-CD3, anti-CD28, and IL-2. This population was subsequently used to
study the differentiation of TGF-beta-producing CD4+ T cells. In further studies,
naive CD4+/LECAM-1high cells from TCR transgenic mice of both the BALB/c and
B10.A backgrounds were stimulated with T-depleted spleen cells (TDS) and specific
peptide in the presence of various cytokines and/or cytokine antagonists for 5
days, restimulated, and TGF-beta, IL-4, and IFN-gamma production were measured.
Priming conditions favoring high IL-4 production and/or low IFN-gamma production
greatly enhanced TGF-beta production in secondary cultures. Furthermore, the
presence of IL-10 in cultures was associated with an increase in TGF-beta
production following restimulation. The importance of IL-4 and IFN-gamma in
regulating TGF-beta production was confirmed in studies showing that cells from
IFN-gamma(-/-) mice produced more TGF-beta, while cells from IL-4(-/-) mice
produced less TGF-beta compared with wild-type controls. Finally, the addition of
exogenous TGF-beta to priming cultures significantly enhanced the production of
TGF-beta upon restimulation, demonstrating that TGF-beta has a role in self
regulating its own production.
PMID- 9637481
TI - Macrophage-derived nitric oxide regulates T cell activation via reversible
disruption of the Jak3/STAT5 signaling pathway.
AB - Nitric oxide (NO) has been invoked as an important pathogenic factor in a wide
range of immunologically mediated diseases. The present study demonstrates that
macrophage-derived NO may conversely function to fine tune T cell-mediated
inflammation via reversible dephosphorylation of intracellular signaling
molecules, which are involved in the control of T cell proliferation. Thus, T
cells activated in the presence of alveolar macrophages are unable to proliferate
despite expression of IL-2R and secretion of IL-2. This process is reproduced by
the NO generator S-nitroso-N-acetylpenicillamine and is inhibitable by the NO
synthase inhibitor N(G)-methyl-L-arginine. Analysis of T cell lysates by
immunoprecipitation with specific Abs and subsequent immunoblotting indicated
marked reduction of tyrosine phosphorylation of Jak3 and STAT5 mediated by NO.
Further studies indicated that NO-mediated T cell suppression was reversible by
the guanylate cyclase inhibitors methylene blue and LY-83583 and was reproduced
by a cell-permeable analogue of cyclic GMP, implicating guanylate cyclase
activation as a key step in the inhibition of T cell activation by NO.
PMID- 9637482
TI - The trophic action of IL-7 on pro-T cells: inhibition of apoptosis of pro-T1,
T2, and -T3 cells correlates with Bcl-2 and Bax levels and is independent of Fas
and p53 pathways.
AB - Signals from the IL-7R are essential for normal thymocyte development. We
isolated thymocytes from early developmental stages and observed that suspensions
of pro-T1, -T2, and -T3 cells rapidly died in culture. Addition of IL-7 promoted
their survival, but did not induce cell division. Pro-T4 cells did not undergo
rapid cell death, and their survival was therefore independent of IL-7. Death in
the absence of IL-7 showed the hallmarks of apoptosis, including DNA
fragmentation and annexin V binding; however, caspase inhibitors blocked DNA
fragmentation, but did not block cell death. The trophic effect of IL-7 was
partially inhibited by blocking protein synthesis. The p53 pathway was not
involved in this death pathway, since pro-T cells from p53-/- mice also underwent
cell death in the absence of IL-7. The Fas/Fas ligand pathway was not involved in
cell death, since Fas-deficient pro-T cells died normally in the absence of IL-7,
anti-Fas Abs did not protect cells from death in the absence of IL-7, and Fas
expression was undetectable on cells at these stages. The IL-7 trophic affect
correlated with increased intracellular levels of Bcl-2 and decreased levels of
Bax, whereas no Bcl-X(L), Bcl-w, or Bad was detectable. Thus, maintaining a
favorable Bcl-2/Bax ratio may account for the trophic action of IL-7.
PMID- 9637484
TI - Immunologic characterization of CD7-deficient mice.
AB - Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK
lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid
development and function, the exact function of CD7 in vivo has remained elusive.
One patient has been reported with SCID syndrome attributed to CD7 deficiency. To
study in vivo functions of CD7, we have generated CD7-deficient mice and assessed
their lymphoid development and function. CD7-deficient mice were viable, had
normal peripheral blood and spleen lymphocyte numbers, and had normal specific Ab
responses with Ag-driven Ig isotype switching. Thymocyte numbers were normal in 4
wk-old, 6-mo-old, and 1-yr-old CD7-deficient mice, but in 3-mo-old CD7-deficient
mice, total thymocyte numbers were significantly increased by 60% (p < 0.02)
compared with normal age-matched +/+ littermates. CD7-deficient splenocytes
proliferated normally in response to various mitogens, including PHA, anti-CD3,
Con A, and LPS. While NK cell numbers and cytolytic activity to YAC targets were
normal, CD7-deficient mice had lower Ag-induced MHC class I-restricted CTL
activity against OVA-transfected target cells than did +/+ control mice. Thus,
CD7-deficient mice did not have a SCID syndrome, but rather had transient
increases in thymocyte numbers at age 3 mo and altered splenocyte Ag-specific CTL
effecter cell activity. These data suggest a role for CD7 in regulating
intrathymic T cell development and in mediating CTL effecter function.
PMID- 9637483
TI - Targeting the IL-15 receptor with an antagonist IL-15 mutant/Fc gamma2a protein
blocks delayed-type hypersensitivity.
AB - Owing to shared receptor components, the biologic activities of IL-15 are similar
to those of IL-2. However, the patterns of tissue expression of IL-2/IL-2R alpha
and IL-15/IL-15R alpha differ. The development of agents targeting the receptor
and signaling elements of IL-15 may provide a new perspective for treatment of
diseases associated with expression of IL-15/IL-15R. We designed, genetically
constructed, and expressed a receptor site-specific IL-15 antagonist by mutating
glutamine residues within the C terminus of IL-15 to aspartic acid and
genetically linked this mutant IL-15 to murine Fc gamma2a. These mutant IL-15
proteins specifically bind to the IL-15R, competitively inhibit IL-15-triggered
cell proliferation, and do not activate the STAT-signaling pathway. Because the
receptor site-specific antagonist IL-15 mutant/Fc gamma2a fusion proteins had a
prolonged t(1/2) in vivo and the potential for destruction of IL-15R+ leukocytes,
we examined the immunosuppressive activity of this agent. An IL-15 mutant/Fc
gamma2a fusion protein markedly attenuated Ag-specific delayed-type
hypersensitivity responses and decreased leukocyte infiltration within the
delayed-type hypersensitivity sites. These findings suggest that 1) IL-15/IL-15R+
cells are crucial to these T cell-dependent immune responses, and 2) treatment
with IL-15 mutant/Fc gamma2a protein may ameliorate T cell-dependent
immune/inflammatory diseases.
PMID- 9637485
TI - Antigen activation rescues recent thymic emigrants from programmed cell death in
the BB rat.
AB - One of the diabetes susceptibility genes of the BB rat is a mutation at the lyp
locus that decreases the thymic output of T cells and the life span of most
recent thymic emigrants (RTE). Consequently, there is a 10-fold reduction in the
number of CD4+ and CD8+ T cells in secondary lymphoid organs. Results presented
in this work demonstrate that the BB rat lyp mutation is associated with an
accelerated apoptotic death in vitro of mature CD4+ 8- and CD4- 8+ thymocytes and
peripheral T cells. The stability of the pool of recirculating T cells (PRL) of
BB rats over time results from a > 10-fold increase in the mitotic activity of T
cells as assessed in vivo by bromodeoxyuridine incorporation. This increased
mitotic activity is not observed when BB T cells develop in the context of a
normal sized PRL. MHC haploidentical WF and BB rats differ at minor
histocompatibility loci. Intravenous injection of (WF x BB)F1 T cells into
euthymic BB rats led to the rejection of donor T cells within 3 wk by unprimed
recipients and within 1 wk by primed recipients. This secondary immune response
was unaffected by postpriming thymectomy. F1 T cells were not rejected, but
rather expanded after their injection into thymectomized BB rats that had been
primed as early as 48 h after thymectomy. These results strongly suggest that the
BB rat PRL is devoid of long-lived naive T cells and that rescue of recent thymic
emigrants from programmed cell death is initiated by Ags, exclusively.
PMID- 9637486
TI - Thymus requirement and antigen dependency in the "infectious" tolerance pathway
in transplant recipients.
AB - We have shown that features of infectious tolerance, as originally described in
thymectomized mice, may be applied to euthymic rat recipients of heart
transplants. We now report on studies aimed at exposing mechanisms underlying the
infectious tolerance pathway, with emphasis on the role of thymus and
alloantigen. Pretransplant thymectomy diminished the efficacy of CD4-targeted
therapy, with donor-specific tolerance induced in approximately 50% of
recipients. Thymus was required for generation of regulatory T cells under the
cover of CD4 mAb therapy and for the ability of these cells to confer infectious
tolerance. However, thymus was not mandatory to maintain an infectious-permissive
environment in cohorts of adoptively transferred recipients. Intragraft
expression of IL-2, IL-4, and IL-10 genes was diminished in euthymic and
thymectomized tolerant hosts. However, grafts in the latter group showed
significant IFN-gamma gene expression, suggesting a less efficient down
regulation of Th1-like cells in the absence of regulatory cells. Indeed,
exogenous challenge with rIL-2 or freshly alloactivated spleen cells recreated
rejection in thymectomized, but not euthymic, hosts, suggesting that a state of
cytokine-responsive anergy contributes to the "noninfectious" form of tolerance
in thymectomized rats. The infection-tolerant state did not result from "graft
adaptation," and regulatory T cells restricted for the original alloantigen were
exposed to its continuous stimulation. The effective memory for suppression was
dependent upon persistent donor-specific alloantigen stimulation; it disappeared
within 3 weeks after its removal. Hence, both central and peripheral immune
mechanisms, orchestrated by the tolerizing alloantigen, contribute to the
infectious tolerance pathway in CD4 mAb-treated rat transplant recipients.
PMID- 9637487
TI - IL-3 enhances both presentation of exogenous particulate antigen in association
with class I major histocompatibility antigen and generation of primary tumor
specific cytolytic T lymphocytes.
AB - Recent studies have reported that APC can present particulate exogenous Ag in the
context of class I MHC to CD8+ CTL, and our laboratory demonstrated that IL-3
could enhance CTL generation to exogenous Ag. In this paper, we wished to
determine whether presentation of particulate Ag could be enhanced by IL-3. A T
cell hybridoma, B3Z86/90.14 (B3Z) restricted to Ova/Kb, was used as an indicator
for presentation of particulate Ag with class I MHC. When activated, this
hybridoma expresses lacZ, allowing a simple colorimetric measurement of Ag
specific T cell stimulation. We demonstrated that bone marrow cells stimulated by
IL-3 in vivo and in vitro exhibited significantly increased presentation of
exogenous OVA linked to beads. Lysate from OVA-transfected line 1 murine lung
adenocarcinoma cells (line 1/OVA) was also presented by IL-3-stimulated bone
marrow cells, suggesting that these APC can process tumor fragments or debris.
Studies using TAP1/2-deficient mice and Ag presentation inhibitors indicate that
this exogenous Ag presentation is mediated via the conventional class I MHC
pathway. Adoptive transfer of IL-3-stimulated bone marrow cells pulsed with
lysate from line 1/OVA tumor cells into naive recipient mice led to the
generation of a potent CTL response. These observations indicate that use of such
cells may provide a new avenue for development of tumor vaccines.
PMID- 9637488
TI - Cooperation between CD44 and LFA-1/CD11a adhesion receptors in lymphokine
activated killer cell cytotoxicity.
AB - IL-2-activated NK cells exhibit cytotoxic activity against a wide variety of
tumor cells in a non-MHC-restricted fashion and in the absence of prior
sensitization. The molecular mechanisms that regulate the cytotoxicity and
attachment of activated killer cells to tumor target cells are not known. We
provide genetic evidence in CD44(-/-) and LFA-1(-/-) mice that the cell adhesion
receptors LFA-1 and CD44 regulate the cytotoxic activity of IL-2-activated NK
cells against a variety of different tumor cells. This defect in cytotoxicity was
significantly enhanced in mice that carried a double mutation of both CD44 and
LFA-1. In vitro differentiation, TNF-alpha and IFN-gamma production, and
expression of the cytolytic effector molecules perforin and Fas-L were comparable
among IL-2-activated NK cells from LFA-1(-/-), CD44(-/-), CD44(-/-)LFA-1(-/-),
and control mice. However, CD44(-/-), LFA-1(-/-), and CD44(-/-)LFA-1(-/-) IL-2
activated NK cells showed impaired binding and conjugate formation with target
cells. We also show that hyaluronic acid is the principal ligand on tumor cells
for CD44-mediated cytotoxicity of IL-2-activated NK cells. These results provide
the first genetic evidence of the role of adhesion receptors in IL-2-activated NK
killing. These data also indicate that distinct adhesion receptors cooperate to
mediate binding between effector and target cells required for the initiation of
"natural" cytotoxicity.
PMID- 9637489
TI - Differential involvement of a Fas-CPP32-like protease pathway in apoptosis of
TCR/CD9-costimulated, naive T cells and TCR-restimulated, activated T cells.
AB - Our previous study showed that CD9 costimulation of TCR-triggered naive T cells
elicits activation ([3H]TdR incorporation) that is similar to CD28 costimulation;
however, unlike CD28 costimulation, CD9 costimulation results in apoptosis of
these previously activated T cells. Here, we investigated whether the apoptosis
occurring after TCR/CD9 stimulation is associated with a death pathway involving
Fas stimulation and Fas-mediated caspase activation as observed in activation
induced cell death (AICD). In contrast to AICD, the apoptosis resulting from
TCR/CD9 stimulation in C57BL/6 T cells was independent of Fas, because this form
of apoptosis was not prevented by anti-Fas ligand mAb and was also induced in
MRL/lpr T cells. AICD was observed at 12 h after the restimulation of activated T
cells with anti-CD3 and reached a peak level at 24 h after this restimulation.
CPP32-like protease activity was detected during AICD. Although TCR/CD9
stimulation-associated apoptosis was observed at 24 h after the stimulation of
naive T cells and reached a peak level at 36 h after this stimulation, CPP32-like
protease activity in these T cells was only marginal at all time points.
Nevertheless, both forms of apoptosis were prevented similarly by two different
peptide-based caspase inhibitors. These results indicate that the apoptosis that
follows the T cell activation which is induced as a result of CD9 costimulation
does not involve a Fas-CPP32-like protease pathway, but suggest that different
caspase members are likely to be critical in this form of apoptosis.
PMID- 9637490
TI - Intracellular formation and cell surface expression of a complex of an intact
lysosomal protein and MHC class II molecules.
AB - The generation of invariant chain-free MHC class II molecules and their
association with endocytically generated peptides are thought to occur in
specialized lysosome-like compartments called MIICs (MHC class II compartments).
A number of in vitro studies have shown that large denatured proteins can bind to
class II molecules, and that class II association can protect the bound segment
of protein from proteolytic degradation. In this work, we present what we believe
is the first example of an intact endogenous protein (IP30) binding in an allele
dependent fashion to class II molecules in vivo. IP30 is an IFN-gamma-inducible
35-kDa glycoprotein that localizes in MIICs. In this study, we show that intact
IP30 binds to certain HLA-DR alleles via an N-terminal prosequence. The
association takes place in the endocytic pathway following removal of invariant
chain from class II molecules and before their cell surface expression. We also
show that DR-IP30 complexes are SDS stable. The potential precursor-product
relationship between DR-IP30 complexes and the DR-peptide complex is discussed.
PMID- 9637491
TI - Relationships among TCR ligand potency, thresholds for effector function
elicitation, and the quality of early signaling events in human T cells.
AB - Determining how receptor ligand quality and quantity together control the
biologic responses of T cells is central to understanding normal and pathologic T
cell immunity. Here we have carefully examined how variations in antigenic
peptide structure and dose affect multiple functional responses of human T cell
clones and have correlated these observations with proximal TCR signaling events
induced by the same set of related ligands. As the Ag concentration increases,
effector functions are elicited according to a clone-specific hierarchy. The
absolute amount of each peptide required to stimulate the entire set of effector
functions (potency) differs markedly among ligands for a single TCR, correlating
with the efficiency of TCR down-modulation and the extent of ZAP-70 activation.
However, distinct patterns of TCR zeta-chain phosphorylation were observed, with
the ratios of TCRzeta isoforms relating to ligand agonist potency. The appearance
of partially phosphorylated TCRzeta isoforms was paralleled by relative changes
in certain response thresholds within the hierarchy. Thus, a combination of
density, potency, and quality of signaling all contribute to the distinct effects
of agonist ligands on T cell immunity.
PMID- 9637492
TI - Expanding dendritic cells in vivo enhances the induction of oral tolerance.
AB - The intestine is under perpetual challenge from both pathogens and essential
nutrients, yet the mucosal immune system is able to discriminate effectively
between harmful and innocuous Ags. It is likely that this selective
immunoregulation is dependent on the nature of the APC at sites where gut Ags are
processed and presented. Dendritic cells (DC) are considered the most potent of
APC and are renowned for their immunostimulatory role in the initiation of immune
responses. To investigate the role of DC in regulating the homeostatic balance
between mucosal immunity and tolerance, we treated mice with Flt3 ligand (Flt3L),
a growth factor that expands DC in vivo, and assessed subsequent systemic immune
responsiveness using mouse models of oral tolerance. Surprisingly, mice treated
with Flt3L to expand DC exhibited more profound systemic tolerance after they
were fed soluble Ag. Most notably, tolerance could be induced in Flt3L-treated
mice using very low doses of Ag that were ineffective in control animals. These
findings contrast with the generally accepted view of DC as immunostimulatory APC
and furthermore suggest a pivotal role for DC during the induction of tolerance
following mucosal administration of Ag.
PMID- 9637493
TI - NK cell modulation of murine cytomegalovirus retinitis.
AB - CMV retinitis, the most common ophthalmic infection of AIDS patients, causes
blindness if left untreated. To study the role of NK cells in the modulation of
CMV ocular infection, 9.0 x 10(2) plaque-forming units of the Smith strain of
murine CMV (MCMV) was injected into the supraciliary space of the left eyes of
BALB/c mice. Lysis of NK-sensitive target cells (YAC-1) by effectors from the
draining lymph nodes peaked at day 5 postinfection, while the splenic cytolytic
response was biphasic, with peaks at days 2 and 7 postinfection. Flow cytometry
showed that NK cells (DX-5+) increased in spleens and eyes 5 days after
supraciliary infection with MCMV compared with uninfected or mock-infected
controls. Eight days after supraciliary injection with 9.0 x 10(2) plaque-forming
units of MCMV, 7 of 10 NK-depleted mice developed retinitis compared with only 2
of 10 non-NK-depleted control mice. Poly(I-C) activation of NK cells in T cell
depleted animals protected mice from MCMV retinitis; only 2 of 10 mice in the
poly(I-C)-treated group developed retinitis compared with 8 of 10 T cell
depleted, non-poly(I-C)-treated control mice. These results show the importance
of NK cells in preventing MCMV retinitis and suggest that NK cells may also be
involved in modulation of cytomegalovirus retinitis in human patients.
PMID- 9637494
TI - T cell renewal rates, telomerase, and telomere length shortening.
AB - Measurements on the average telomere lengths of normal human naive and memory T
cells suggested that 1) naive and memory human T cells have similar division
rates, and 2) that the difference between naive and memory cells reflects the
degree of clonal expansion during normal immune reactions. Here we develop
mathematic models describing how the population average of telomere length
depends on the cell division rates of naive and memory T cells during clonal
expansion and normal renewal. The results show that 1) telomeres shorten with
twice the cell division rate, 2) that the conventional approach of estimating
telomere length shortening per mean population doubling gives rise to estimates
that are 39% larger than the "true" loss per cell division, 3) that naive and
memory T cells are expected to shorten their telomeres at rates set by the
division rate of the naive T cells only, i.e., irrespective of the division rate
of memory T cells, 4) that the measured difference in the average telomere length
between naive and memory T cells may largely reflect the difference in renewal
rates between these subpopulations rather than the clonal expansion, and 5) that
full telomerase compensation during clonal expansion is consistent with all data
on the shortening of telomere length in, and between, naive and memory T cells.
Thus we reconcile the apparent contradictions between the demonstrated difference
in division rates between human naive and memory T cells and their similar rates
of telomere shortening, and the demonstrated telomere shortening in the presence
of telomerase activity.
PMID- 9637495
TI - High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic
diabetes-prone BioBreeding rats.
AB - Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune
diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear
rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic
and circulate severely reduced numbers of T cells. Peripheral T cells present are
phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-BB
recent thymic emigrants have a shortened life span and disappear by apoptosis.
The percentage of T cells with an alphabetaTCR(low) B220+ CD4- CD8- phenotype was
increased in DP peripheral lymphoid tissues when compared with normal,
nonlymphopenic diabetes-resistant (DR) BB rat tissues. There was no evidence of
DNA fragmentation in freshly isolated DP- or DR-BB rat cells, but, after 24 h of
culture, a higher proportion of DP- than DR-BB splenic T cells underwent
apoptosis. We then tested the hypothesis that BB rat T cells with the
alphabetaTCR(low) B220+ CD4- CD8- phenotype accumulate and undergo apoptosis in
the liver. Such cells were observed undergoing apoptosis in both DP- and DR-BB
rats, but comprised approximately 80% of intrahepatic T cells in DP vs
approximately 20% in DR-BB rats. Most alphabetaTCR(low) B220+ CD4- CD8- cells in
the liver were also Thy1+. The data suggest that T cell apoptosis in the DP-BB
rat is underway in peripheral lymphoid tissues and is completed in the liver.
Increased intrahepatic apoptosis of recent thymic emigrants appears in part
responsible for lymphopenia in DP-BB rats and the concomitant predisposition of
these animals to autoimmunity.
PMID- 9637496
TI - The generation of human gammadelta T cell repertoires during fetal development.
AB - The nature of how human gammadelta T cells are normally generated is not clear.
We have used an RT-PCR assay and DNA sequencing to identify and compare delta
encoded TCRs (TCRDs) that are generated de novo in the fetal gut, liver, and
thymus and to determine when, where, and how the TCRD repertoire is established
during normal embryonic development. Rearranged TCRDV genes are first expressed
outside of the thymus in the liver and primitive gut between 6 and 9 wk
gestation. Although DV1Rs and/or DV2Rs predominated, differences in the pattern
of TCRDV gene rearrangement and transcription in each tissue during ontogeny were
identified. Specific, DV2-encoded TCRs are highly conserved throughout ontogeny
in the tissues from the same and between genetically distinct donors. Although
the thymic and intestinal gammadelta T cell repertoires partially overlap early
in development, they diverge and become nonoverlapping during the second
trimester, and the generation of the intestinal gammadelta T cell repertoire is
characterized by differences in the processing of DV1Rs and DV2Rs. Whereas the
structural diversity of DV1Rs progressively increases during gut development up
to birth, DV2Rs have limited structural diversity throughout ontogeny. Together,
our findings provide evidence for the ability of different fetal tissues to
support the development of gammadelta T cells.
PMID- 9637497
TI - Exogenous and endogenous IL-10 regulate IFN-alpha production by peripheral blood
mononuclear cells in response to viral stimulation.
AB - IL-10 is an important regulator of the production of proinflammatory cytokines.
Its effect on IFN-alpha production, however, has not been reported. In this
study, PBMC from healthy donors were stimulated with virus in the presence of IL
10. Human IL-10 (hIL-10) caused reductions in both the frequency of IFN-alpha
producing cells (IPC) and bulk IFN in response to herpes simplex virus type-1
(HSV-1), Sendai virus, Newcastle disease virus, and vesicular stomatitis virus.
The inhibitory effect occurred when IL-10 was added 2 or 4 h before, or 2 h
poststimulation with HSV or Sendai virus, but not when added 4 h postinduction.
Unlike IL-10, IL-4 did not affect the IFN-alpha response to HSV. However, when
PBMC were induced with Sendai virus, IFN-alpha production was also reduced by IL
4. IL-10 treatment of PBMC resulted in strong reductions in the steady state
levels of both HSV- and Sendai virus-induced IFN-alpha1, -alpha2, and -beta mRNA
as determined by RT-PCR. IFN-alpha production to Sendai virus occurs
predominantly by monocytes, whereas most enveloped viruses stimulate low
frequency "natural IFN-producing cells (NIPC)," which are thought to be dendritic
cells. Peripheral blood dendritic cells were found to express the IL-10 receptor,
suggesting that IL-10 may directly act on the dendritic IPC. Addition of
monoclonal anti-IL-10 to PBMC resulted in a significant increase in both the
frequency of IPC and the amount of secreted IFN-alpha in response to HSV but not
Sendai virus. We conclude that human IL-10 can serve as both an endogenous and
exogenous regulator of IFN-alpha production.
PMID- 9637498
TI - A pathogenic role of Th2 cells and their cytokine products on the pulmonary
metastasis of murine B16 melanoma.
AB - The role of Th2 cells and the cytokines produced by these cells on experimental
pulmonary metastasis of B16 melanoma was investigated in a murine model implanted
with high metastatic (B16F10) or low metastatic (B16F1) melanoma cells. An
average of 250 colonies of metastasis in the lungs was counted in mice (BF10
mice) at 14 days after the inoculation of 2 x 10(5) B16F10 cells/mouse, while <20
colonies were detected in mice (BF1 mice) inoculated with the same number of
B16F1 cells. CD4+ CD11b+ TCR-alphabeta+ T cells (BF10-Th2 cells) were produced in
the spleens of BF10 mice, while these cells were not detected in BF1 mice. The
BF10-Th2 cells produced IL-4 and IL-10 into culture fluids when stimulated in
vitro with anti-CD3 mAb. However, IL-2 and IFN-gamma were not produced. The level
of a pulmonary metastasis in BF1 mice increased to the level observed in BF10
mice, when BF10-Th2 cells were adoptively transferred to BF1 mice. Also, an
increase in the number of pulmonary melanoma was demonstrated in BF1 mice treated
with 10 microg/kg murine rIL-4. The level of pulmonary metastasis in BF10 mice or
in BF1 mice inoculated with BF10-Th2 cells decreased to the level observed in BF1
mice when mice were treated with an anti-IL-4 mAb at a dose of 250 microg/kg on
days 1, 3, and 5 after tumor inoculation. These results suggest that the severity
of pulmonary metastasis in mice receiving B16 melanoma cells is strongly
influenced by the IL-4 released from tumor-associated Th2 cells.
PMID- 9637499
TI - IL-16 activates the SAPK signaling pathway in CD4+ macrophages.
AB - IL-16 has been reported as a modulator of T cell activation and was shown to
function as chemoattractant factor. The chemotactic activity of IL-16 depends on
the expression of CD4 on the surface of target cells, but the intracellular
signaling pathways are only now being deciphered. This report describes IL-16 as
an additional activator of the stress-activated protein kinase (SAPK) pathway in
CD4+ macrophages. Treatment of these cells with recombinant expressed IL-16 leads
to the phosphorylation of SEK-1, resulting in activation of the SAPKs p46 and
p54. IL-16 stimulation also leads to the phosphorylation of c-Jun and p38 MAPK
(mitogen-activated protein kinase), without inducing MAPK-family members ERK-1
and ERK-2. Interestingly, the IL-16-mediated activation of SAPKs and p38 MAPK in
macrophages alone induces no detectable apoptotic cell death. These observations
suggest specific regulatory functions of IL-16 distinct from the proinflammatory
cytokines TNF-alpha and IL-1beta.
PMID- 9637500
TI - Dipeptidyl peptidase I and granzyme A are coordinately expressed during CD8+ T
cell development and differentiation.
AB - Dipeptidyl peptidase I (DPPI) is a granule protease that plays a requisite role
in processing the proenzyme form of the CTL granule serine proteases (granzymes).
This study assesses DPPI mRNA and enzyme expression during T lymphocyte ontogeny
and CTL differentiation. The most immature CD3- CD4- CD8- thymocytes were found
to express >40-fold higher levels of DPPI mRNA, although levels of DPPI enzymatic
activity in CD3- CD4- CD8- thymocytes were only modestly higher than those seen
for CD4+ CD8+ or CD4+ CD8- thymocytes. More mature CD8+ CD4- thymocytes and CD8+
splenocytes expressed significantly higher levels of DPPI mRNA and enzymatic
activity than CD4+ CD8+ or CD4+ CD8- thymocytes. Granzyme A mRNA expression was
observed in DPPI expressing CD3- CD4- CD8- and CD8+ CD4- thymocytes and was also
observed in CD8+ CD4- splenocytes; however, expression was not observed in CD4+
CD8+ or CD4+ CD8- thymocytes. Both DPPI mRNA and granzyme A mRNA expression in
CD8+ T cells decreased to very low or undetectable levels during the first 48 h
after allostimulation in MLCs. However, peak levels of both DPPI and granzyme A
expression were observed later in the course of CD8+ T cell responses to
alloantigen, with DPPI mRNA expression peaking on either day 3 or day 4 and
granzyme A expression peaking at the end of a 5-day MLR. These data indicate that
DPPI is expressed at all stages of T cell ontogeny and differentiation in which
granzyme A mRNA is detected; consequently, DPPI appears to be available for the
processing and activation of granzyme A during both CD8+ T cell development and
differentiation.
PMID- 9637501
TI - Stromal cell-independent maturation of IL-7-responsive pro-B cells.
AB - The proliferation, survival, and differentiation of B cell progenitors in primary
hematopoietic tissues depends on extracellular signals produced by stromal cells
within the microenvironment. IL-7 is a stromal-derived growth factor that plays a
crucial role in B lineage development. We have shown that in the presence of IL
7, pro-B cells proliferate and differentiate to a stage in which they are
responsive to stromal cells and LPS, leading to terminally differentiated IgM
secreting plasma cells. In this report, we examine in detail the role of stromal
cells in the transition from the IL-7-responsive pro-B cell stage to the mature
LPS-responsive B cell stage. We demonstrate that this transition fails to occur,
even in the presence of stromal cells and LPS, if constant exposure to IL-7 is
maintained. The transition from the large pro-B cell stage to the small cmu+ pre
B cell stage occurs independent of stromal cells. Moreover, the "stromal cell
dependent" maturation that occurs subsequent to the expression of surface IgM
leading to responsiveness to B cell mitogens can also be accomplished in the
absence of stromal cells if pre-B cells are cultured in proximity to each other
or at high cell concentrations. Together these results suggest that stromal cells
mediate B cell differentiation by providing the necessary growth requirements
(i.e., IL-7) to sustain the development of pre-B cells. The progeny of these pre
B cells can then differentiate through as yet unidentified homotypic
interactions, leading to the production of LPS-responsive B cells.
PMID- 9637502
TI - CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous
apoptosis and promote cell cycle entry.
AB - Isolated murine splenic B cells undergo spontaneous apoptosis. Motifs containing
unmethylated CpG dinucleotides in bacterial DNA or in synthetic
oligodeoxynucleotides (ODN) are known to activate murine B cells. Now we show
that ODN that induce spleen B cell cycle entry also inhibit spontaneous apoptosis
in a sequence-specific fashion. Reversal of the CG to GC abolished activity.
Methylation of the central cytosine decreased activity. When CpG is preceded by a
cytosine or followed by a guanine, activity was abolished. Other substitutions at
the same positions had no effect. Dose-response curves for apoptosis protection
and G1 entry suggested that a uniform population of ODN recognition sites
controlled downstream ODN effects. A CpG ODN with a nuclease-resistant
phosphorothioate backbone (S-ODN) was also active, and increased the levels of c
myc, egr-1, c-jun, bclXL, and bax mRNA and c-Myc, c-Jun, Bax, and BclXL protein
in spleen B cells. Levels of c-myb, myn, c-Ki-ras, and bcl2 mRNA remained
unchanged. When protein synthesis was inhibited, at 16 h ODN-induced cell cycle
entry was abolished and apoptosis protection was partially preserved. Under these
conditions, c-Myc was still present, but c-Jun and BclXL were not detected. Our
results suggest that CpG containing ODN motifs provide signals for both survival
and cell cycle entry. Single base changes determine whether this signal proceeds
through a rate-limiting step governing at least two steps in apoptosis (plasma
membrane transition, DNA cleavage) and two phases of the cell cycle (G1 and S
phase entry). This biologic action is associated with increased c-Myc, c-Jun, and
BclXL expression.
PMID- 9637503
TI - The regulation of murine H-2Dd expression by activation transcription factor 1
and cAMP response element binding protein.
AB - Resistance to radiation leukemia virus (RadLV)-induced leukemia is correlated
with an increase in H-2Dd expression on the thymocyte surface. It has been shown
that elevated H-2Dd expression on infected thymocytes is a result of elevated
mRNA transcription and that the transcriptional increase is correlated with
elevated levels of a DNA binding activity, H-2 binding factor 1 (H-2 BF1), which
recognizes the 5'-flanking sequence (5'-TGACGCG-3') of the H-2Dd gene. Recently,
it has been shown that the activation transcription factor 1 (ATF-1) homodimer is
one form of the H-2 BF1 complex. Here we demonstrate that the cAMP response
element binding protein (CREB) homodimer and the heterodimer of CREB/ATF-1 also
recognize the cis regulatory motif and are two additional forms of the H-2 BF1
complex. The levels of mRNA encoding ATF-1 and CREB were both increased in RadLV
infected thymocytes that showed increased levels of H-2 mRNA. Also, all three H-2
BF1 binding activities, ATF-1 homodimer, CREB homodimer, and ATF-1/CREB
heterodimer, were increased in RadLV-infected thymocytes that expressed high
levels of H-2Dd Ag on the cell surface. Transfection experiments demonstrated
that ATF-1 and CREB activated a reporter plasmid containing the H-2 BF1 motif.
These observations strongly suggest that both ATF-1 and CREB are involved in the
regulation of H-2 gene expression following RadLV infection of mouse thymocytes.
PMID- 9637504
TI - Expression and characterization of recombinant soluble peptide: I-A complexes
associated with murine experimental autoimmune diseases.
AB - Structural and functional studies of murine MHC class II I-A molecules have been
limited by the low yield and instability of soluble, recombinant heterodimers. In
the murine autoimmune diseases experimental autoimmune encephalomyelitis and
collagen-induced arthritis, MHC class II molecules I-Au and I-Aq present peptides
derived from myelin basic protein and type II collagen, respectively, to
autoreactive T cells. To date, systems for the expression of these two I-A
molecules in soluble form for use in structure-function relationship studies have
not been reported. In the present study, we have expressed functional I-Au and I
Aq molecules using a baculovirus insect cell system. The chain pairing and
stability of the molecules were increased by covalently linking the antigenic
peptides to beta-chains and adding carboxyl-terminal leucine zippers. Peptide:I
Aq complex quantitatively formed an SDS-stable dimer, whereas peptide:I-Au formed
undetectable amounts. However, the two complexes did not show any significant
difference in their response to thermal denaturation as assessed by circular
dichroism analyses. The autoantigen peptide:I-A complexes were highly active in
stimulating cognate T cells to secrete IL-2 and inducing Ag-specific apoptosis of
the T cells. Interestingly, the T cells were stimulated by these soluble
molecules in the apparent absence of experimentally induced cross-linking of
TCRs, indicating that they may have therapeutic potential in autoimmune disease
models.
PMID- 9637505
TI - HLA-G isoforms produced by placental cytotrophoblasts and found in amniotic fluid
are due to unusual glycosylation.
AB - The human placenta expresses HLA-G, a nonclassical (class Ib) MHC molecule that
could play a central role in maternal tolerance of the semiallogeneic fetus. In
this work, we report the production of a new mAb, 4H84, that specifically reacts
with HLA-G in two formats: immunocytochemistry and immunoblotting.
Immunolocalization experiments with 4H84 confirmed our previous finding that
cytotrophoblasts within the uterine wall are the only cells in tissue sections of
placenta that express the HLA-G protein. Additional experiments showed that both
amniocytes and cytotrophoblasts in the amnion-chorion express this protein. Since
multiple HLA-G transcripts have been described, we used immunoblotting to study
the HLA-G isoforms produced by cytotrophoblasts in vitro and by the amnion
chorion in vivo. Cytotrophoblasts, their conditioned medium, and amniotic fluid
samples contained heterodisperse immunoreactive bands (Mr 35,000-50,000). N
deglycosylation by peptide-N-glycosidase F digestion resolved these isoforms into
two distinct bands. Cell samples contained primarily an Mr 37,000-42,000 protein,
most likely encoded by the full-length mRNA. Conditioned medium and amniotic
fluid contained a slightly smaller protein, most likely the secreted form lacking
the transmembrane and cytoplasmic regions. Removal of polylactosamine chains by
endo-beta D-galactosidase digestion significantly reduced the electrophoretic
mobility of the immunoreactive bands, suggesting that HLA-G, unlike class Ib
molecules studied to date, carries N-acetyllactosamine units. These data show
that Mr heterogeneity of HLA-G is due to its novel glycosylation, rather than to
the translation of alternatively spliced mRNAs. We postulate that the unusual
carbohydrate structures this molecule carries could interact with maternal immune
cells and/or stabilize the molecule.
PMID- 9637506
TI - Failure to activate cytosolic phospholipase A2 causes TNF resistance in human
leukemic cells.
AB - Activation of cytosolic phospholipase A2 (cPLA2) by TNF has been shown to be an
important component of the signaling pathway leading to cell death. The role of
cPLA2 in the cytotoxic action of TNF was investigated in a panel of human
leukemic cell lines. TNF could activate cPLA2 only in U937 and HL60 TNF-sensitive
leukemic cells, but not in KG1a, CEM, and CEM/VLB100 cells that are relatively
resistant to TNF. Pretreatment with 4-bromophenacyl bromide, a cPLA2 inhibitor,
rendered U937 and HL60 cell lines resistant to the cytotoxic effect of TNF.
Immunoblot and reverse-transcriptase PCR demonstrated that cPLA2 expression was
detectable at both transcriptional and translational levels in all leukemic cell
lines studied, although CEM and CEM/VLB100 cells expressed cPLA2 mRNA and protein
at lower levels. The protein synthesis inhibitor, cycloheximide, increased TNF
induced cPLA2 activity and cytotoxicity in both CEM and CEM/VLB100 cell lines.
Low levels of cPLA2 activity in the KG1a cell line could be activated by the
cPLA2 activator mellitin, or the calcium ionophore A23187. The data suggest that
cPLA2 activity is involved in TNF-induced cytotoxicity in leukemic cells.
Resistance to TNF-induced cytotoxicity may involve either protein inhibitors that
act upstream of cPLA2 in the TNF-signaling pathway or constitutive defects of
cPLA2 itself, possibly involving calcium utilization.
PMID- 9637507
TI - Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10.
AB - Exogenously added IL-10 rapidly inhibited Staphylococcus aureus- or LPS-induced
cytokine mRNA expression in human PBMCs and monocytes, with a maximal effect
observed when IL-10 was added from 20 h before until 1 h after the addition of
the inducers. Nuclear run-on assays revealed that the inhibition of IL-12 p40, IL
12 p35, and TNF-alpha was at the gene transcriptional level and that the addition
of IL-10 to S. aureus- or LPS-treated PBMCs did not affect mRNA stability. The
inhibitory activity of IL-10 was abrogated by cycloheximide (CHX), suggesting the
involvement of a newly synthesized protein(s). The addition of CHX at 2 h before
S. aureus or LPS also inhibited the accumulation of IL-12 p40 mRNA, but did not
inhibit IL-12 p35 and TNF-alpha mRNA. This finding suggests that p40
transcription is regulated through a de novo synthesized protein factor(s),
whereas the addition of CHX at 2 h after S. aureus activation caused
superinduction of the IL-12 p40, IL-12 p35, and TNF-alpha genes. These results
indicate that in human monocytes, the mechanism(s) of IL-10 suppression of both
IL-12 p40 and IL-12 p35 genes is primarily seen at the transcriptional level, and
that the induction of the IL-12 p40 and p35 genes have different requirements for
de novo protein synthesis.
PMID- 9637508
TI - Conservation of structure and function between human and murine IL-16.
AB - IL-16 is a proinflammatory cytokine that signals via CD4, inducing chemotactic
and immunomodulatory responses of CD4+ lymphocytes, monocytes, and eosinophils.
Comparative analysis of murine and human IL-16 homologs could reveal conserved
structures that would help to identify key functional regions of these cytokines.
To that end, we cloned the murine IL-16 cDNA and found a high degree of amino
acid similarity comparing the predicted murine and human IL-16 precursor proteins
(pro-IL-16). The highest similarity (82.1%) was found in the C-terminal region,
which is cleaved from pro-IL-16 to yield biologically active IL-16. Chemotaxis
experiments with IL-16 of murine and human origin, using murine splenocytes or
human T lymphocytes as targets, showed cross-species stimulation of motility.
Synthetic oligopeptides and anti-peptide Ab were produced, based on the sequences
of three predicted hydrophilic domains of IL-16 potentially presented in exposed
positions. None of these peptides had intrinsic IL-16 bioactivity, but one
(corresponding to a hydrophilic C-terminal domain of IL-16) partially displaced
binding of OKT4 mAb to human lymphocytes. This peptide, and its cognate Ab, also
inhibited IL-16 chemoattractant activity for human and murine cells. These
studies demonstrate a high degree of structural and functional similarity between
human and murine IL-16 and suggest that amino acids in the C terminus are
critical for its chemoattractant function. The data suggest cross-species
conservation of IL-16 receptor structures as well. Inhibitory peptides may be
useful in disease states where the proinflammatory functions of IL-16 are
detrimental to the host.
PMID- 9637509
TI - The effect of gammadelta T cell depletion on cytokine gene expression in
experimental allergic encephalomyelitis.
AB - In experimental autoimmune encephalomyelitis (EAE), a model for multiple
sclerosis, we showed previously that depletion of gammadelta T cells using the
mAb GL3 immediately before disease onset, or during the chronic phase,
significantly ameliorated clinical severity. We now report on the effect of
gammadelta T cell depletion on expression of five cytokine genes, IL-1, IL-6,
TNF, lymphotoxin, and IFN-gamma in spinal cords of mice during the pre-onset,
onset, height, and recovery phases of EAE, and on expression of type II nitric
oxide synthase. In control animals, the mRNAs for IL-1 and IL-6 rose dramatically
at disease onset and peaked before disease height, whereas the mRNAs for TNF,
lymphotoxin, and IFN-gamma rose more slowly and peaked with peak of disease. In
GL3-treated animals, a dramatic reduction in all five cytokines was noted at
disease onset, but only IFN-gamma remained significantly reduced at a time point
equivalent to height of disease in control animals. ELISA data confirmed the
reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and
pathologic analysis demonstrated a marked reduction in meningeal infiltrates at
the same time point. Studies of type II NOS also demonstrated a significant
reduction in both mRNA and protein expression at the height of disease in GL3
treated animals. These results suggest that gammadelta T cells contribute to the
pathogenesis of EAE by regulating the influx of inflammatory cells into the
spinal cord and by augmenting the proinflammatory cytokine profile of the
inflammatory infiltrates.
PMID- 9637510
TI - Inefficient assembly and intracellular accumulation of antibodies with mutations
in V(H) CDR2.
AB - We previously described secretion defects in four mutants of the murine anti
phosphocholine Ab, T15. The mutant heavy (H) chains had amino acid replacements
in the V(H) complementarity-determining region 2 (HCDR2) and were expressed at
normal intracellular levels. Here, the intracellular fate of the secretion
defective mutant heavy chains was investigated. Metabolic labeling demonstrated
that the T15 wild-type Ab was secreted within a 4-h chase. In contrast, the
mutant H chains accumulated with intracellular t(1/2) values ranging from 10 to
24 h. The mutant H chains were associated with increased levels of the molecular
chaperones BiP and GRP94, and remained endoglycosidase H sensitive, suggesting
retention in the endoplasmic reticulum. Assembly of the mutant H chains with T15
light (L) chain was arrested at the H2 and H2L intermediate stages of the T15
wild-type pathway (H2 --> H2L --> H2L2). Even though some assembly with L chain
occurred, it was not as a secretion-competent H2L2 Ig moiety. The T15 L chains
coexpressed with mutant H chains were degraded efficiently except for a minor L
chain population with a long t(1/2) that was apparently protected at the H2L
stage. To our knowledge, this is the first study demonstrating that intracellular
half-lives of Ig H and L chains can be influenced by somatic mutations in HCDR2.
PMID- 9637512
TI - Structural and functional analysis of J chain-deficient IgM.
AB - Previous studies have discerned two forms of polymeric mouse IgM: moderately
cytolytic (complement-activating) pentamer, which contains J chain, and highly
cytolytic hexamer, which lacks J chain. To investigate the relationships among
polymeric structure, J chain content, and cytolytic activity, we produced IgM in
J chain-deficient and J chain-proficient mouse hybridoma cell lines. Both hexamer
and pentamer were produced in the absence as well as the presence of J chain.
Hexameric IgM activated (guinea pig) complement approximately 100-fold more
efficiently than did J chain-deficient pentamer, which, in turn, was more active
than J chain-containing pentamer. These results are consistent with the
hypothesis that J chain-containing pentamer cannot activate complement. We also
analyzed the structure of IgM-S337, in which the mu-chain bears the C337S
substitution. Like normal IgM, IgM-S337 was formed as a hexamer and as both J
chain deficient- and J chain-containing pentamers. Unlike normal IgM, IgM-S337
dissociated in SDS into various subunits. For IgM-S337 pentamer, the predominant
subunits migrated as mu2kappa2 and mu4kappa4, and the subunit distribution was
unaltered by J chain. However, J chain was found only in the mu2kappa2 species,
suggesting that some arrangement of inter-mu bonds directs incorporation of J
chain. IgM-S337 hexamer also dissociated to mu2kappa2 and mu4kappa4, but also
yielded several species migrating much more slowly in SDS-PAGE than wild-type
mu12kappa12. To account for these forms, we propose that each mu-chain can
interact with three other mu-chains and that some hexameric molecules contain two
catenated mu6kappa6 circles.
PMID- 9637511
TI - The alpha2 domain of H-2Dd restricts the allelic specificity of the murine NK
cell inhibitory receptor Ly-49A.
AB - Mouse NK lymphocytes express Ly-49 receptors, which inhibit cytotoxicity upon
ligation by specific MHC I molecules on targets. Different members of the lectin
like mouse Ly-49 receptor family recognize distinct subsets of murine H-2
molecules, but the molecular basis for the allelic specificity of Ly-49 has not
been defined. We analyzed inhibition of natural killing by chimeric MHC I
molecules in which the alpha1, alpha2, or alpha3 domains of the Ly-49A-binding
allele H-2Dd were exchanged for the corresponding domains of the nonbinding
allele H-2Db. Using the Ly-49A-transfected rat NK cell line, RNK-mLy-49A.9, we
demonstrated that the H-2Dd alpha2 domain alone accounts for allelic specificity
in protection of rat YB2/0 targets in vitro. We also showed that the H-2Dd alpha2
domain is sufficient to account for the allele-specific in vivo protection of H
2b mouse RBL-5 tumors from NK cell-mediated rejection in D8 mice. Thus, in
striking contrast to the alpha1 specificity of Ig-like killer inhibitory
receptors for human HLA, the lectin-like mouse Ly-49A receptor is predominantly
restricted by the H-2Dd alpha2 domain in vitro and in vivo.
PMID- 9637513
TI - Structural requirements for a specificity switch and for maintenance of affinity
using mutational analysis of a phage-displayed anti-arsonate antibody of Fab
heavy chain first complementarity-determining region.
AB - We previously showed that a single mutation at heavy (H) position 35 of Abs
specific for p-azophenylarsonate (Ars) resulted in acquisition of binding to the
structurally related hapten p-azophenylsulfonate (Sulf). To explore the sequence
and structural diversity of the H chain first complementarity-determining region
(HCDR1) in modulating affinity and specificity, positions 30-36 in Ab 36-65 were
randomly mutated and expressed as Fab in a bacteriophage display vector. Ab 36-65
is germline encoded, lacking somatic mutations. Following affinity selection on
Sulf resins, 55 mutant Fab were isolated, revealing seven unique HCDR1 sequences
containing different amino acids at position H:35. All Fab bound Sulf, but not
Ars. Site-directed mutagenesis in a variety of HCDR1 sequence contexts indicates
that H:35 is critical for hapten specificity, independent of the sequence of the
remainder of HCDR1. At H:35, Asn is required for Ars specificity, consistent with
the x-ray crystal structure of the somatically mutated anti-Ars Ab 36-71, while
Sulf binding occurs with at least seven different H:35 residues. All Sulf-binding
clones selected following phage display contained H:Gly33, observed previously
for Ars-binding Abs that use the same germline V(H) sequence. Site-directed
mutagenesis at H:33 indicates that Gly plays an essential structural role in
HCDR1 for both Sulf- and Ars-specific Abs.
PMID- 9637515
TI - Mechanisms of macrophage stimulation through CD8: macrophage CD8alpha and CD8beta
induce nitric oxide production and associated killing of the parasite Leishmania
major.
AB - Prior studies demonstrated that rat macrophages express CD8, which differs from T
lymphocyte CD8 within the ligand binding domain. We investigated whether
stimulation of macrophage CD8 could induce mediator release and regulate host
defense. Cross-linking either CD8alpha (OX8, 5 microg/ml) or CD8beta (341, 10
microg/ml) stimulated nitric oxide (NO) production, which correlated with an up
regulation of inducible NO synthase protein. Cell signaling inhibitors were used
to elucidate the pathways of CD8alpha and CD8beta stimulation. Genistein (broad
spectrum protein tyrosine kinase inhibitor, 10 microg/ml), PP1 (src family kinase
inhibitor, 5 microg/ml), polymyxin B (protein kinase C (PKC) inhibitor, 100
microg/ml), and Ro 31-8220 (PKC inhibitor, 1 microM) significantly inhibited anti
CD8alpha- and anti-CD8beta-stimulated NO production and inducible NO synthase up
regulation, suggesting that tyrosine kinase(s) (src family) and PKC are involved
in CD8 signaling. In addition, cross-linking CD8alpha stimulated NO-dependent
macrophage killing of the parasite Leishmania major. For the first time, this
work demonstrates that the beta-chain of macrophage CD8, in addition to the alpha
chain, can regulate mediator release. These results further illustrate the
importance of this molecule and support our previous data demonstrating
differences between macrophage and T lymphocyte CD8. Additional studies on the
signaling mechanisms and possible ligand(s) for macrophage CD8 will lead to a
greater understanding of inflammation and host defense.
PMID- 9637514
TI - Role of mucosal immunity in herpes simplex virus infection.
AB - This study evaluates whether the vaginal mucosal surface of immunized mice can
prevent invasion by herpes simplex virus (HSV) and aims to identify immune
components that affect immunity after challenge at the vaginal mucosa. Despite
the induction of both IgA and IgG vaginal Ab following immunization with
recombinant vaccinia virus vectors expressing either glycoproteins B or D, viral
infection occurred in most animals even after minimal viral dose challenge.
Challenged immune animals, including those genetically unable to generate anti
HSV Ab, survived and showed few if any clinical signs of infection. Experiments
with T cell subtype knockout animals and depletion with T cell subset-specific
MAb indicated that immunity following vaginal challenge was principally dependent
on the function of CD4+ T cells. Our results indicate that anti-HSV vaccines may
not provide barrier immunity at the vaginal mucosal site but may be adequate to
minimize clinical expression of disease.
PMID- 9637516
TI - The role of T cells in allografted tumor rejection: IFN-gamma released from T
cells is essential for induction of effector macrophages in the rejection site.
AB - Allografted Meth A tumor rejection is T cell dependent, but T cells are inactive
toward the allograft; rather, the main effector cells are allograft-induced
macrophages (AIM) with MHC haplotype specificity. Here, we examined the role of T
cells in the induction of AIM in the rejection site. On day 4.5 after i.p.
transplantation of Meth A fibrosarcoma cells to C57BL/6 (B6) mice, we obtained a
kind of precursor of AIM (pro-AIM) from the transplantation site by an enrichment
technique involving adherence to serum-coated dishes. The noncytotoxic pro-AIM
rich population put into a diffusion chamber became cytotoxic against Meth A
cells after 2 days in the peritoneal cavity of an untreated B6 mouse. Similar
activation of the chambered B6 pro-AIM-rich population occurred in IFN-gamma -/-
B6 mice, whereas there was no activation when chambers containing an IFN-gamma -/
mouse-derived pro-AIM-rich population were placed in normal or IFN-gamma -/-
mice, suggesting that IFN-gamma is involved in the activation. RT-PCR experiments
demonstrated that among bulk infiltrates T cells were the major producer of IFN
gamma; and most of the cells in a T cell-eliminated pro-AIM population in a
diffusion chamber kept for 2 days in a B6 mouse did not become AIM. Furthermore,
IFN-gamma -/- B6 mice could not reject allografted Meth A tumor cells, whereas
the grafts were rejected by i.p. injections of IFN-gamma into the mutant mice.
These results indicate that IFN-gamma released from allograft-induced T cells is
essential for both the activation of a kind of pro-AIM to AIM in the
transplantation site and the rejection of an allografted tumor.
PMID- 9637517
TI - Mucosal addressin is required for the development of diabetes in nonobese
diabetic mice.
AB - Immune responses are best initiated in the environment of lymphoid tissues
wherein circulating lymphocytes enter by interacting with endothelial adhesion
molecules. In type 1 diabetes, immune responses against pancreatic islets
develop, but the environment in which this occurs remains unidentified. To
determine whether lymphocyte homing to lymphoid organs is involved in the
pathogenesis of diabetes in nonobese diabetic (NOD) mice, we blocked the function
of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is a vascular
addressin-mediating lymphocyte homing into mucosal lymphoid tissues, in these
mice. While ineffective if started later, a blockade started at 3 wk of age
reduced the incidence of diabetes from 50% to 9% (p < 0.01). This finding is
associated with Peyer's patch atrophy, a marked decrease of naive (CD44(low)
CD45RB(high)) T lymphocytes, and a reduction in the relative numbers of memory
(CD44(high)) T lymphocytes in the spleen. The potential of these spleen cells to
cause diabetes was diminished. Anti-MAdCAM-1 treatment also inhibited both
lymphocyte entry into the pancreas and diabetes development in NOD/SCID
recipients after the transfer of lymphocytes derived from the mesenteric lymph
nodes of young, but not of diabetic, NOD donors. Therefore, MAdCAM-1 may be
required during two distinct steps in an early phase of diabetes development: for
the entry of naive lymphocytes into the lymphoid tissues in which diabetes
causing lymphocytes are originally primed, and for the subsequent homing of these
lymphocytes into the pancreas. The role of MAdCAM-1 as a mucosal vascular
addressin suggests that mucosal lymphoid tissues are involved in the initiation
of pathologic immune responses in NOD mice.
PMID- 9637518
TI - The antibody response to fungal melanin in mice.
AB - Melanins are associated with virulence in several important human pathogens, but
little is known about the immune response to this ubiquitous biologic compound.
We hypothesized that melanin produced by the fungus Cryptococcus neoformans was
immunogenic. C. neoformans melanin was purified from melanized fungal cells and
was used to immunize C57BL/6, BALB/c, and T cell-deficient (nude) BALB/c mice.
The Ab response was evaluated by ELISA, immunofluorescence, and agglutination.
The results demonstrate that melanin can be immunogenic, and the humoral immune
response is T cell independent. Furthermore, the experiments demonstrate 1) a
sensitive ELISA for the measurement of Ab to melanin, 2) that mice mount an
intense Ab response to fungal melanin that includes Abs of IgM and IgG isotypes,
3) that melanins from different sources have cross-reactive epitopes, and 4)
melanin in the cell wall of melanized yeast cells reacts with Abs raised to L
dopa C. neoformans melanin. The biologic significance of Ab to melanin remains to
be determined, but the development of Ab suggests that this amorphous insoluble
polymer can stimulate the immune system. The serologic techniques described here
may prove useful for the evaluation of Ab responses to melanin in a variety of
diseases.
PMID- 9637519
TI - Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN
gamma gene expression in human T cells.
AB - T cells contribute significantly the to host's early defense against viral and
bacterial infections and are essential for clearance of the pathogen. IFN-gamma,
a product of activated T and NK cells, has, in addition to its direct
antimicrobial activity, a major role in activating cell-mediated immunity. Here
we report that cytokines secreted by influenza A virus-infected macrophages are
able to induce IFN-gamma synthesis in human T cells. Influenza A virus-infected
human peripheral macrophages secreted IFN-alpha/beta, TNF-alpha, IL-1beta, and a
recently identified cytokine, IL-18 (or IFN-gamma-inducing factor), whereas the
production of IL-12 was not detected. Supernatants collected from virus-infected
macrophages induced rapid IFN-gamma mRNA expression and protein production in T
cells. This was down-regulated by the addition of neutralizing anti-IFN
alpha/beta Abs, whereas neutralizing anti-IL-12 Abs had no effect on IFN-gamma
gene expression. Exogenously added IFN-alpha/beta also rapidly stimulated the
synthesis of IFN-gamma mRNA in T cells independently of protein synthesis. IL-18
synergized with IFN-alpha to up-regulate IFN-gamma gene expression and protein
production. The data suggest that IFN-alpha/beta and IL-18 produced by
macrophages during virus infection may act together to induce IFN-gamma synthesis
and, consequently, may play an important role for both of these cytokines in the
development of Th1-type immune responses.
PMID- 9637520
TI - Clostridium difficile toxin A stimulates macrophage-inflammatory protein-2
production in rat intestinal epithelial cells.
AB - Neutrophil infiltration of the colonic mucosa is a hallmark of Clostridium
difficile toxin A-mediated enterocolitis. Macrophage-inflammatory protein-2 (MIP
2) is a potent neutrophil chemoattractant secreted by rat macrophages and
epithelial cells in response to inflammatory stimuli. In this work, we report
that administration of toxin A into rat ileal loops increased mucosal levels of
MIP-2 before the onset of fluid secretion and mucosal neutrophil infiltration.
Administration of rabbit anti-MIP-2 IgG, but not control IgG, reduced toxin A
mediated secretion (by 58%), mucosal permeability (by 80%), and myeloperoxidase
activity (by 85%). Immunohistochemical analysis demonstrated increased MIP-2
expression in intestinal epithelial and lamina propria cells 1 h after toxin A
administration. Intestinal epithelial cells purified from toxin A-exposed ileal
loops also showed increased MIP-2 mRNA expression and MIP-2 protein release that
was inhibited by pretreatment of rats with the transcriptional inhibitor
actinomycin D. These results indicate that C. difficile toxin A induces MIP-2
release from intestinal epithelial cells and that MIP-2 contributes to neutrophil
mucosal influx during toxin A enteritis.
PMID- 9637521
TI - Th1 cells specific for a secreted protein of Listeria monocytogenes are
protective in vivo.
AB - In the present study we have investigated the role of the secreted p60 protein
from Listeria monocytogenes as an Ag for CD4 T cells. The p60 protein is an
abundant extracellular protein that is highly conserved within the members of the
genus Listeria. Our results show that L. monocytogenes infection induces a potent
p60-specific Th1 immune response. Remarkably, we found that p60-specific Th1
clones mediate significant protection against L. monocytogenes infection. For one
p60-specific clone, the peptide epitope was defined. This clone recognized p60
301-312 (EAAKPAPAPSTN) in the context of the H-2Ad molecule. Despite the fact
that acquired immunity against L. monocytogenes is primarily mediated by
cytotoxic CD8 T lymphocytes, our data clearly demonstrate that secreted bacterial
proteins are important CD4 T cell Ags and that Th1 clones specific for a secreted
bacterial protein can contribute to the protection against an intracellular
pathogen such as L. monocytogenes.
PMID- 9637522
TI - IL-6 produced by Kupffer cells induces STAT protein activation in hepatocytes
early during the course of systemic listerial infections.
AB - Kupffer cells were the principal source of IL-6 produced in the livers of mice
following i.v. inoculation of Listeria monocytogenes. IL-6 mRNA expression and
the production of IL-6 were reduced drastically within the nonparenchymal liver
cell population derived from mice rendered Kupffer cell depleted by pretreatment
with liposome-encapsulated dichloromethylene diphosphonate. A sharp increase in
the appearance of activated STAT3 occurred in extracts of purified hepatocytes
derived from normal mice infected i.v. with Listeria. Remarkably, the kinetics of
this increase overlapped IL-6 mRNA expression by Kupffer cells; each peaked at
approximately 30 min postinfection. No increase in STAT3 activation was observed
in IL-6-deficient or Kupffer cell-depleted animals. The results of these
experiments indicate that the synthesis of IL-6 and the activation of STAT3
within hepatocytes are critical functions of Kupffer cells occurring very early
during the course of systemic listerial infections.
PMID- 9637523
TI - Characterization of the peptide binding motif of a rhesus MHC class I molecule
(Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency
virus.
AB - The majority of immunogenic CTL epitopes bind to MHC class I molecules with high
affinity. However, peptides longer or shorter than the optimal epitope rarely
bind with high affinity. Therefore, identification of optimal CTL epitopes from
pathogens may ultimately be critical for inducing strong CTL responses and
developing epitope-based vaccines. The SIV-infected rhesus macaque is an
excellent animal model for HIV infection of humans. Although a number of CTL
epitopes have been mapped in SIV-infected rhesus macaques, the optimal epitopes
have not been well defined, and their anchor residues are unknown. We have now
defined the optimal SIV gag CTL epitope restricted by the rhesus MHC class I
molecule Mamu-A*01 and defined a general peptide binding motif for this molecule
that is characterized by a dominant position 3 anchor (proline). We used peptide
elution and sequencing, peptide binding assays, and bulk and clonal CTL assays to
demonstrate that the optimal Mamu-A*01-restricted SIV gag CTL epitope was
CTPYDINQM(181-189). Mamu-A*01 is unique in that it is found at a high frequency
in rhesus macaques, and all SIV-infected Mamu-A*01-positive rhesus macaques
studied to date develop an immunodominant gag-specific CTL response restricted by
this molecule. Identification of the optimal SIV gag CTL epitope will be critical
for a variety of studies designed to induce CD8+ CTL responses specific for SIV
in the rhesus macaque.
PMID- 9637524
TI - Blockade of endogenous TNF-alpha exacerbates primary and secondary pulmonary
histoplasmosis by differential mechanisms.
AB - We investigated the mechanisms by which endogenous TNF-alpha modulates host
defenses during experimental primary and secondary pulmonary infection with
Histoplasma capsulatum (Hc). Neutralization of TNF-alpha in vivo resulted in
increased CFU and 100% mortality in naive and immune mice challenged with Hc
intranasally. Levels of IFN-gamma and granulocyte macrophage-CSF were elevated in
TNF-alpha-neutralized naive mice, whereas IL-4, -6, -10 and TGF-beta did not
differ from controls. In contrast, in secondary histoplasmosis, significant
elevations of IL-4 and -10 were observed in TNF-alpha-depleted mice. Alveolar
macrophages (Mphi) did not exert fungistatic activity against Hc after exposure
to recombinant murine TNF-alpha, recombinant murine IFN-gamma, or both. The
increase in susceptibility to primary Hc infection was associated with diminished
production of reactive nitrogen intermediates by alveolar Mphi from TNF-alpha
depleted mice, whereas production of nitric oxide during secondary histoplasmosis
was similar in both groups. Upon secondary challenge, TNF-alpha-depleted mice
were rescued by concomitant neutralization of IL-4 and IL-10, but not either
cytokine alone. Thus, TNF-alpha is critical for controlling primary and secondary
infection with Hc, and the mechanisms that lead mice to succumb to primary or
secondary infection when endogenous TNF-alpha is blocked are different.
PMID- 9637525
TI - Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced
apoptosis in human B cells.
AB - To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated
and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma
cell line Ramos with different apoptosis sensitivities. Selection for sensitivity
to Fas-induced apoptosis also selected for clones with enhanced BCR death
sensitivity and vice versa. In contrast, clones resistant to Fas-mediated
apoptosis could still undergo BCR-induced cell death. Based on the functional
phenotypes of these clones, we hypothesized that both receptor-induced apoptosis
pathways are initially distinct but may eventually converge. Indeed, ligation of
both Fas and BCR resulted in cleavage of the IL-1beta-converting enzyme/Ced-3
like protease caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and
poly(ADP-ribose) polymerase. Markedly, qualitative differences in the caspase 3
cleavage pattern induced by Fas or BCR ligation were observed; whereas Fas
ligation generated caspase 3 cleavage products of 19/20 and 17 kDa, only the
latter cleavage product was found upon BCR cross-linking. The caspase inhibitor
Val-Ala-Asp-fluoromethylketone blocked both Fas- and BCR-mediated apoptosis, but
differentially affected caspase 3 cleavage induced by either stimulus. Finally,
overexpression of a Fas-associated death domain (FADD) dominant-negative mutant
protein was found to inhibit Fas-induced apoptosis but not BCR-induced apoptosis.
Together our findings imply that Fas and BCR couple, via FADD-dependent and FADD
independent mechanisms, respectively, to distinct proteases upstream of caspase
3.
PMID- 9637526
TI - T lymphocytes are required for protection of the vaginal mucosae and sensory
ganglia of immune mice against reinfection with herpes simplex virus type 2.
AB - Intravaginal inoculation of mice with an attenuated strain of herpes simplex
virus type 2 (HSV-2) resulted in vigorous HSV-specific immune responses that
protected against subsequent challenge with fully virulent HSV-2 strains. Even in
the presence of high titers of HSV-specific Ab, T cell-dependent mechanisms were
required for protection of the vaginal mucosae of HSV-immune mice and could be
detected by 24 h after intravaginal reinoculation. Depletion of specific T cell
subsets from HSV-immune mice before HSV-2 reinoculation demonstrated that CD4+ T
cells were primarily responsible for this protection. Similarly, optimal
protection of the sensory ganglia against reinfection with HSV-2 was dependent on
the presence of T cells. Infectious HSV-2 was not detected in the sensory ganglia
or spinal cord of HSV-immune mice depleted of only CD4+ or CD8+ T cells,
suggesting that the T cell-mediated protection could be provided by either
subset. Similarly, neutralization of IFN-gamma during challenge of HSV-immune
mice resulted in diminished protection of the vaginal mucosa, but not of the
sensory ganglia. These results suggest that the ability to induce vigorous HSV
specific T cell responses is an important consideration in the design of vaccines
to protect both the vaginal mucosa and sensory ganglia against HSV-2.
PMID- 9637527
TI - Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune
protection during pulmonary infection by Mycobacterium bovis bacille Calmette
Guerin in IL-12-deficient mice.
AB - Understanding of key cytokines and the nature of protective immune responses in
pulmonary mycobacterial diseases remains a task of paramount importance. In this
study, both wild-type (wt) and IL-12-deficient (IL-12(-/-)) mice were infected by
airways inoculation of live Mycobacterium bovis bacille Calmette-Guerin (BCG).
The type 1 cytokines IL-12, IFN-gamma, and TNF-alpha, but not the type 2
cytokines IL-4 and granulocyte macrophage (GM)-CSF, markedly increased in the
lung and peripheral blood of wt mice postinfection, which resulted in the
development of intense granulomatous responses and the effective control of
mycobacterial infection in the lung. In contrast, IL-12(-/-) mice demonstrated a
lack of both types 1 and 2 cytokines in the lung and blood and a severely
impaired tissue immune-inflammatory response lacking not only macrophages and
neutrophils but CD4 and CD8 T cells and NK cells in the lung throughout the
entire course of study. Total lung mononuclear cells isolated from these mice, in
contrast to wt mice, had an impaired recall immune response to Ag challenge in
vitro. These impaired responses resulted in an uncontrolled local growth and
systemic spread of bacilli. Our findings reveal that IL-12 plays an irreplaceable
role in the initiation of Th1 responses, and the loss of its function cannot be
compensated for by alternative mechanisms in the lung. This cytokine, together
with IFN-gamma and TNF-alpha, and granulomatous inflammation are critically
required for the effective control of pulmonary mycobacterial infection. Our
results also indicate that the absence of type 1 cytokines does not necessarily
favor a Th2 response.
PMID- 9637528
TI - Altered intestinal immune system but normal antibacterial resistance in the
absence of P-selectin and ICAM-1.
AB - ICAM-1 and P-selectin are adhesion molecules that regulate leukocyte migration,
extravasation to inflammatory sites, and other immune cell interactions. T cell
mediated resistance against acute infection with Listeria monocytogenes and
chronic infection with Mycobacterium bovis Calmette-Guerin bacillus was
investigated in mutant mice lacking P-selectin and/or ICAM-1. Mice deficient in P
selectin (Psel-/-), ICAM-1 (ICAM-/-), or the combination of both (Psel-/- x ICAM
/-) showed normal bacterial clearance, comparable delayed-type hypersensitivity
reactions, and equivalent memory T cell responses. Additionally, the distribution
of alpahbeta vs gammadelta T lymphocyte populations was examined. Normal
lymphocyte distributions were noted in thymus, spleen, and blood, whereas mutant
mice showed marked alterations in the intestinal intraepithelial (i-IEL) and
lamina propria lymphocytes. Differences in i-IEL populations were reflected
functionally by differential lytic activities and cytokine productions of i-IEL
populations from mutant mice. Despite these changes within the mucosal immune
system of mutant mice, their resistance against oral infection with L.
monocytogenes was apparently unimpaired. These findings demonstrate that P
selectin and ICAM-1 are critically involved in the shaping of lymphocyte
populations of the gut but have only a minor influence on systemic and regional
host defense against intracellular bacteria.
PMID- 9637529
TI - IL-4-dependent regulation of TGF-alpha and TGF-beta1 expression in human
eosinophils.
AB - TGFs play important roles in wound healing and carcinogenesis. We have previously
demonstrated that eosinophils infiltrating into different pathologic processes
elaborate TGF-alpha and TGF-beta1. Eosinophils infiltrating hamster cutaneous
wounds were found to express TGFs sequentially. In this study, we examined the
biologic mediators that may regulate the expression of TGF-alpha and -beta1 by
eosinophils. Eosinophils were isolated from the peripheral blood of healthy
donors and cultured in the absence or presence of IL-3, IL-4, and IL-5. Cells
were analyzed by in situ hybridization and immunohistochemistry. Supernatants
from these cultures were assayed for secreted TGF-alpha and TGF-beta1 using TGF
specific ELISAs. IL-3, IL-4, and IL-5 independently up-regulated TGF-beta1 mRNA
and product expression by eosinophils in all donors. Interestingly, TGF-alpha
production by eosinophils was up-regulated by IL-3 and IL-5 but was down
regulated by IL-4. Consistent with the ability of IL-4 to regulate eosinophil
responses, IL-4 signaling molecules are present in human eosinophils. The
observation that IL-4 can differentially regulate the expression of TGF-alpha and
TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF
expression by the infiltrating eosinophils in wound healing and carcinogenesis.
PMID- 9637530
TI - Complement activation occurs on subendothelial extracellular matrix in vitro and
is initiated by retraction or removal of overlying endothelial cells.
AB - Vascular endothelium is continuously exposed to plasma complement, which could
generate a potent proinflammatory signal if activated on the vascular wall.
Normal endothelium, however, expresses an anti-inflammatory phenotype, which
includes resistance to complement fixation. As activated endothelium converts to
a proinflammatory phenotype, we investigated the effect of cytokines on
endothelial susceptibility to complement fixation. Cytokine-treated HUVEC were
exposed to human serum as a source of complement, and C3 deposition was
quantified. IL-1beta and TNF-alpha in combination with IFN-gamma markedly
increased endothelial C3 deposition; however, immunofluorescence microscopy
revealed that the endothelial cells had retracted, and that bound C3 was
concentrated not on cells but in areas of exposed subendothelial extracellular
matrix (ECM). Studies with cell-free ECM indicated that complement activation
required only ECM exposure and was independent of cellular activation. C3
deposition on ECM was reproduced by reconstituting the alternative pathway, which
generated a stable C3 convertase on ECM, but not on endothelial cells. C3b and
iC3b were identified on ECM exposed to purified alternative pathway components
and serum, respectively. In conditions associated with endothelial disruption,
exposure of subendothelial ECM could induce complement fixation and contribute to
inflammation and vascular damage.
PMID- 9637531
TI - Immunization with purified natural and recombinant allergens induces mouse IgG1
antibodies that recognize similar epitopes as human IgE and inhibit the human IgE
allergen interaction and allergen-induced basophil degranulation.
AB - Molecular characterization of allergens by recombinant DNA technology has made
rapid progress in the recent few years. In the present study we immunized mice
with aluminum hydroxide-adsorbed purified recombinant major timothy grass pollen
allergens (rPhl p 1, rPhl p 2, rPhl p 5), dog albumin, a major animal dander
allergen, and proteins with low (beta-lactoglobulin) or no (ribulose diphosphate
carboxylase) allergenic potential in humans. Allergens that bind high levels of
IgE in humans (Phl p 1, Phl p 5, dog albumin) induced high IgE and IgG1 levels in
mice, whereas proteins with little or no allergenic activity in humans failed to
induce significant IgE and IgG1 levels in mice. Continuous immunization for a
period of 27 wk resulted in the production of mouse IgG1 Abs that recognized
recombinant allergen fragments/epitopes defined by IgE Abs of allergic patients.
As a consequence, allergen-specific mouse Abs strongly inhibited human IgE
binding to the allergens and suppressed the allergen-induced histamine release
from human basophils. In summary, our data indicate that 1) the allergenic
potency of a protein may be related to its overall immunogenicity and 2)
prolonged immunization with single purified recombinant allergens induces
protective IgG Abs. The presented experimental in vivo/in vitro system allows the
evaluation of Ag preparations (e.g., recombinant allergens) to be used for
immunotherapy in humans.
PMID- 9637532
TI - Arachidonic acid enhances the tissue factor expression of mononuclear cells by
the cyclo-oxygenase-1 pathway: beneficial effect of n-3 fatty acids.
AB - Monocytes express tissue factor (TF) upon stimulation by inflammatory agents.
Dietary administration of fish oil rich in eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) results in an impairment of TF expression by
monocytes. EPA and DHA are metabolized differently from arachidonic acid (AA),
the major fatty acid present in cell membranes. We examined the effects of AA on
the TF expression of isolated human PBMC, and we determined whether EPA and DHA
modulated this phenomenon differently. Nonstimulated PBMC had a low TF-dependent
procoagulant activity. When PBMC were incubated with increasing concentrations of
AA, the TF-dependent procoagulant activity increased in a dose-dependent manner
to 190% at 7.5 microM. Indomethacin, a cyclo-oxygenase inhibitor, totally
abolished the stimulating effect of AA, whereas specific pharmacologic inhibitors
of cyclo-oxygenase-2 or of 5-lipoxygenase had no inhibitory effect. A thromboxane
(TX)A2/endoperoxides receptor antagonist and a TX synthase inhibitor blocked the
potentiating effect of AA. Purified PGG2 and carbocyclic TXA2, a TXA2 agonist,
enhanced the procoagulant activity of PBMC in a dose-dependent manner whereas, in
contrast, PGE2 inhibited it. Finally, contrary to AA, EPA or DHA did not increase
TXB2 production or TF expression by PBMC. The TF-dependent procoagulant activity
of isolated PBMC was increased by AA through the production of cyclo-oxygenase-1
metabolites; the combined action of PGG2 and TXA2, which potentiated it, was
greater than that of PGE2, which inhibited it. Dietary n-3 fatty acids exert part
of their beneficial effect by modulating this procoagulant activity differently
from AA.
PMID- 9637533
TI - Complement receptor 3 of macrophages is associated with galectin-1-like protein.
AB - We have previously identified a 16-kDa protein with a pI of 5.1 (P16/5.1) that is
associated with macrophage CR3. Microsequencing of P16/5.1 indicated exclusive
homology to the beta-galactoside-binding lectin, galectin-1. Abs specific to a
galectin-1 unique peptide reacted with P16/5.1. The association of P16/5.1 with
CR3 was specifically inhibited by lactose, which binds with high affinity to
galectin-1. These data together with similarities in molecular mass and pI
suggest that P16/5.1 is galectin-1. Two-color immunofluorescence staining
revealed the expression of galectin-1 on the macrophage surface and its
colocalization with CR3. However, a surplus of CR3 was free of galectin-1, and
some galectin-1 molecules were associated with cell surface receptors other than
CR3. Based on these results we propose two models depicting the functional
significance of CR3-galectin-1 association: 1) homodimeric galectin-1 possessing
a divalent sugar binding site may act as an extracellular adapter molecule that
cross-links CR3 with other receptors; and 2) association of galectin-1 with beta
galactosides on the extracellular domain of CR3 may modify the binding affinity
of the receptor to its ligand. These possibilities are not mutually exclusive and
can clarify the mode by which CR3 transmits signals in macrophages.
PMID- 9637534
TI - Physiologic regulation of postovulatory neutrophil migration into vagina in mice
by a C-X-C chemokine(s).
AB - Leukocytes, particularly neutrophils, infiltrate into female genital organs after
ovulation in both humans and mice. In mice, a female sexual cycle consists of 5
phases: proestrus, estrus, metestrus-1, metestrus-2, and diestrus. Ovulation
occurs at estrus; at metestrus-2, a large number of neutrophils infiltrate into
the vaginal epithelium accompanied by an increased neutrophil number in vaginal
lavage fluid. Concomitantly, concentrations of a functional IL-8 homologue,
murine macrophage inflammatory protein (MIP)-2, were increased significantly in
vaginal lavage fluid at metestrus-2 as compared with other phases. On the
contrary, MIP-2 was not detected in plasma during the whole course of a sexual
cycle. Moreover, immunohistochemical analyses demonstrated that MIP-2 protein
expression was prominent at the upper layer of the vaginal epithelium at
metestrus-2, in contrast to a marginal staining in the vaginal epithelium at
proestrus and estrus. These results suggest that a C-X-C chemokine, MIP-2, was
produced physiologically in the vaginal epithelium in a sexual cycle-dependent
manner. Furthermore, the administration of neutralizing anti-IL-8R homologue Abs
at proestrus abrogated leukocyte infiltration into the vagina at metestrus.
However, anti-MIP-2 Abs reduced leukocyte influx at metestrus by approximately
50%. Thus, a murine IL-8 homologue, MIP-2, and its related molecules
physiologically regulate neutrophil migration into the vagina in a sexual cycle
dependent manner.
PMID- 9637535
TI - Novel role of transmembrane SCF for mast cell activation and eotaxin production
in mast cell-fibroblast interactions.
AB - Mast cell activation can be induced by multiple mechanisms, including IgE-,
complement-, and stem cell factor (SCF)-mediated pathways. In addition, the
interaction of mast cells with particular cell populations, such as fibroblasts,
have also demonstrated increased mast cell reactivity. In these studies, we have
investigated the role of fibroblast-mast cell interaction for induction of
histamine release and chemokine production and the specific role of SCF during
this interaction. Primary pulmonary fibroblast cell lines were grown in culture
and used throughout these studies. Mast cells were grown in parallel with
fibroblasts by incubation of bone marrow cells with SCF and IL-3. During mast
cell-fibroblast coculture, increased histamine release could be attenuated either
by separation of the cell populations using a Trans-Well setup, which did not
allow cellular contact, or by specific anti-SCF Ab. In addition, a significant
increase in eotaxin, a potent eosinophil-specific C-C chemokine, was also
observed during fibroblast-mast cell interaction. The production of eotaxin was
cell contact dependent and could be inhibited using an anti-SCF Ab or specific
antisense therapy. SCF was constitutively produced from fibroblasts in its
transmembrane form and could be induced by TNF. SCF-coated plates induced
significant mast cell-derived eotaxin production, whereas soluble SCF induced
little or no eotaxin, suggesting a necessity for receptor cross-linking for
activation. These studies indicate that fibroblast-mast cell contact plays a role
in exacerbation of histamine release and eotaxin production.
PMID- 9637536
TI - Low grade rhinovirus infection induces a prolonged release of IL-8 in pulmonary
epithelium.
AB - Rhinoviruses are important respiratory pathogens implicated in asthma
exacerbations. The mechanisms by which rhinoviruses trigger inflammatory
responses in the lower airway are poorly understood, in particular their ability
to infect the lower airway. Bronchial inflammatory cell (lymphocyte and
eosinophil) recruitment has been demonstrated. IL-8 is a potent proinflammatory
chemokine that is chemotactic for neutrophils, lymphocytes, eosinophils, and
monocytes and may be important in the pathogenesis of virus-induced asthma.
Increased levels of IL-8 have been found in nasal samples in natural and
experimental rhinovirus infections. In these studies we therefore examine the
ability of rhinovirus to infect a transformed lower airway epithelial cell line
(A549) and to induce IL-8 protein release and mRNA induction. We observed that
rhinovirus type 9 is able to undergo full viral replication in A549 cells, and
peak viral titers were found 24 h after inoculation. Rhinovirus infection induced
a dose- and time-dependent IL-8 release up to 5 days after infection and an
increase in IL-8 mRNA expression that was maximal between 3 and 24 h after
infection. UV inactivation of the virus completely inhibited replication, but
only reduced IL-8 protein production and mRNA induction by half, while prevention
of virus-receptor binding completely inhibited virus-induced IL-8 release,
suggesting that part of the observed effects was due to viral replication and
part was due to virus-receptor binding. These studies demonstrate that
rhinoviruses are capable of infecting a pulmonary epithelial cell line and
inducing IL-8 release. These findings may be important in understanding the
pathogenesis of rhinovirus-induced asthma exacerbations.
PMID- 9637537
TI - Role of TNFR1 and TNFR2 in TNF-induced platelet consumption in mice.
AB - An injection of TNF in mice induced profound thrombocytopenia, due to an increase
of platelet consumption, that was evident after 1 h and lasted for 3 days. This
process was evident in mice that were genetically deficient in TNFR2 (p75) but
not in mice lacking TNFR1 (p55), indicating that the process is mediated by TNFR1
bearing cells. To explore the site of action of TNF, labeled platelets from TNFR1
-/- or +/+ donors were transferred to TNFR1 -/- or +/+ recipients. TNF induced
the consumption of platelets from TNFR1 -/- donors when injected into +/+
recipients, while platelets from +/+ donors were not consumed when present in
TNFR1 -/- recipients; this finding indicates that TNF acts on the TNFR1 of host
cells but does not act on platelets. The expression of TNFRs is consistent with
this interpretation, since TNFRs were not detected on platelets by flow
cytometry. In megakaryocytes, the expression of TNFR1 was detected by
immunohistochemistry. These results indicate that TNF induces platelet
consumption by acting not on platelets directly but on the TNFR1 of other cells,
presumably increasing the release of factors with agonist activity for platelets.
PMID- 9637538
TI - An antigen recognized by autologous CTLs on a human bladder carcinoma.
AB - By stimulating blood lymphocytes with autologous bladder carcinoma cells that had
been transfected with B7-1, we obtained a panel of CTL clones which lyse
specifically the bladder tumor cells in an MHC class I-restricted fashion. Based
on inhibition with anti-HLA Abs and the recognition of allogeneic tumor cells, we
could distribute our clones in three groups that recognized three distinct Ags.
We characterized one of these Ags by screening a cDNA library prepared with the
RNA from this bladder tumor line. This new tumor Ag is a peptide presented by HLA
B4403 molecules. It is produced by a point mutation in a gene that is recorded in
databases under the name KIAA0205, is ubiquitously expressed, and whose function
is unknown. We also found this mutation in the tumor sample that was originally
resected from this patient, but the mutation was not found in the 100 or more
independent tumors of various histologic types that were tested. This report is
the first to describe the isolation of CTL clones directed against human bladder
cancer and the molecular characterization of a bladder tumor Ag.
PMID- 9637539
TI - Antibody-IL-12 fusion proteins are effective in SCID mouse models of prostate and
colon carcinoma metastases.
AB - IL-12 is a complex cytokine in both its structure and its range of biologic
activities. Fusions of this heterodimeric molecule with an intact antitumor Ab
were made to test the feasibility and efficacy of targeting IL-12 to tumors to
elicit a local immune response. Fusion proteins composed of the human p35 and p40
subunits had IL-12 bioactivities that were nearly as potent on human immune cells
as the rIL-12 standard, but were inactive on mouse cells. Hybrid IL-12 fusion
proteins composed of mouse p35 and human p40, fused to Ab, were capable of
inducing IFN-gamma, but were much less active on mouse spleen cells than a mouse
IL-12 standard. Despite this relatively low activity, the hybrid fusion protein
was as effective in a SCID mouse model as a fully active Ab-IL-2 fusion protein
in eliminating established pulmonary metastases of CT26 colon carcinoma. Specific
targeting of a human IL-12 fusion protein to metastatic prostate carcinoma
xenografts was also shown to be effective in SCID mice transplanted with human
lymphocyte-activated killer cells. These results demonstrate the importance of
directing this potent cytokine to the tumor microenvironment and suggest an
important alternative to systemic IL-12 administration or gene therapy for
increasing its therapeutic index.
PMID- 9637540
TI - Reconstitution of EBV-specific T cell immunity in solid organ transplant
recipients.
AB - EBV-specific autologous CTL were grown in vitro from three adults (two liver
transplant recipients and one patient on hemodialysis awaiting kidney
retransplant). All CTL lines were TCR alphabeta, CD8 positive cells, EBV
specific, and MHC class I restricted. The CTL lines were expanded in vitro and
infused in three escalating doses (5 x 10(7), 1 x 10(8), and 2 x 10(8) at monthly
intervals. Weekly blood samples were collected following each infusion. EBV
specific CTL precursor cells in peripheral blood were quantitated by limiting
dilution analysis, and their effect on EBV load in vivo was assessed by
semiquantitative PCR. In all three patients, the numbers of CTL precursor cells
increased during the weeks following the infusions and were highest after the
third infusion. This level gradually declined but remained above the preinfusion
levels for up to 3 mo. EBV genome copy number, on the other hand, dropped
following the first infusion and became undetectable thereafter. The EBV DNA
level remained lower than the pretransplant level in all patients for up to 3 mo
after the last infusion. Our study shows that it is feasible to generate and
expand EBV-specific CTL from pretransplant blood samples of solid organ
transplant recipients, that these CTL can be stored and infused posttransplant,
and that they remain cytotoxic and EBV specific in vivo. The aim of this study is
to use these CTL for prevention and treatment of lymphoproliferative disease in
solid organ transplant recipients.
PMID- 9637541
TI - Transfection of the type II TGF-beta receptor into colon cancer cells increases
receptor expression, inhibits cell growth, and reduces the malignant phenotype.
AB - OBJECTIVE: To determine if transfection of SW48 colon cancer cells with the type
II transforming growth factor-beta (TGF-beta) receptor restores growth inhibition
and reverses the in vitro and in vivo malignant phenotype. SUMMARY BACKGROUND
DATA: The authors have previously shown that SW48 colon cancer cells that are
replication error positive in both alleles lack functional cell surface TGF-beta
type I (RI) and type II (RII) receptors and are insensitive to TGF-beta1-induced
growth inhibition. METHODS: SW48 cells were stably transfected with the cDNA for
the normal type II TGF-beta receptor (RII). Once transfected, the cells were
evaluated for in vitro phenotypic changes and in vivo changes in tumor growth.
RESULTS: Denaturing sequencing gel electrophoresis of the reverse transcriptase
polymerase chain reaction product from SW48 cells revealed that the RII coding
sequence contained a single base deletion mutation. When these cells were
transfected with normal RII cDNA, Northern and Western blot analyses revealed
increased levels of RII mRNA and protein. Affinity labeling techniques revealed
that RII-transfected SW48 cells produced functional RI and RII protein.
Transfection of SW48 cells also led to changes in cell phenotype, as shown by
inhibition of both in vitro growth rate and incorporation of [3H]-thymidine. SW48
cells expressing normal RII also exhibited reduced cloning efficiency in
semisolid medium and reduced growth as a xenograft in NOD/LtSz-scid/J mice.
CONCLUSIONS: The results confirm that RII is a tumor-suppressor protein that is
required for TGF-beta-induced growth inhibition in SW48 colon cancer cells.
PMID- 9637542
TI - Testosterone: the crucial hormone responsible for depressing myocardial function
in males after trauma-hemorrhage.
AB - OBJECTIVE: To determine whether testosterone depletion in males before trauma
hemorrhage has any salutary effects on cardiac performance after hemorrhage and
resuscitation. SUMMARY BACKGROUND DATA: Studies indicate that castration of male
mice before trauma-hemorrhage prevents the immunodepression seen after hemorrhage
and resuscitation. However, the effect of precastration on cardiac performance
under such conditions remains unknown. METHODS: Male rats were castrated or sham
castrated 14 days before the experiment. After laparotomy (i.e., induction of
trauma), the rats were bled to and maintained at a mean arterial pressure of 40
mm Hg until 40% of the maximal shed volume was returned in the form of Ringer's
lactate solution. The animals were then resuscitated with four times the shed
blood volume with Ringer's lactate solution over 60 minutes. Heart performance
was measured using a left ventricular catheter connected to an in vivo heart
performance analyzer. Indices of left ventricular performance (i.e., maximal rate
of the pressure increase [+dP/dt(max)] and decrease [-dP/dt(max)) were measured
up to 4 hours after trauma, hemorrhagic shock, and resuscitation. RESULTS: In
sham-castrated animals, trauma-hemorrhage and resuscitation decreased the in vivo
heart performance as evidenced by the reduced values of +dP/dt(max) and
dP/dt(max). Precastrated animals, however, showed significantly higher values of
+dP/dt(max) and -dP/dt(max) than sham-castrated animals after trauma-hemorrhage
and resuscitation. CONCLUSIONS: Testosterone antagonism in males might be an
effective approach for maintaining myocardial function after adverse circulatory
conditions. Although testosterone depletion in male trauma victims is neither
practical nor advocated, testosterone receptor blockade after trauma may
represent a novel and useful adjunct for maintaining normal myocardial
performance under those conditions.
PMID- 9637543
TI - Surgical treatment of adenocarcinoma of the rectum.
AB - OBJECTIVE: The authors' aim was to determine survival and recurrence rates in
patients undergoing resection of rectal cancer achieved by abdominoperineal
resection (APR), coloanal anastomosis (CAA), and anterior resection (AR) without
adjuvant therapy. SUMMARY BACKGROUND DATA: The surgery of rectal cancer is
controversial; so, too, is its adjuvant management. Questions such as
preoperative versus postoperative radiation versus no radiation are key. An
approach in which the entire mesorectum is excised has been proposed as yielding
low recurrence rates. METHODS: Of 1423 patients with resected rectal cancers, 491
patients were excluded, leaving 932 with a primary adenocarcinoma of the rectum
treated at Mayo. Eighty-six percent were resected for cure. Surgery plus adjuvant
treatment was performed in 418, surgery alone in 514. These 514 patients are the
subject of this review. Among the 514 patients who underwent surgery alone, APR
was performed in 169, CAA in 19, AR in 272, and other procedures in 54. Eighty
seven percent of patients were operated on with curative intent. The mean follow
up was 5.6 years; follow-up was complete in 92%. APR and CAA were performed
excising the envelope of rectal mesentery posteriorly and the supporting tissues
laterally from the sacral promontory to the pelvic floor. AR was performed using
an appropriately wide rectal mesentery resection technique if the tumor was high;
if the tumor was in the middle or low rectum, all mesentery was resected. The
mean distal margin achieved by AR was 3 +/- 2 cm. RESULTS: Mortality was 2% (12
of 514). Anastomotic leaks after AR occurred in 5% (16 of 291) and overall
transient urinary retention in 15%. Eleven percent of patients had a wound
infection (abdominal and perineal wound, 30-day, purulence, or cellulitis). The
local recurrence and 5-year disease-free survival rates were 7% and 78%,
respectively, after AR; 6% and 83%, respectively, after CAA; and 4% and 80%,
respectively, after APR. Patients with stage III disease, had a 60% disease-free
survival rate. CONCLUSIONS: Complete resection of the envelope of supporting
tissues about the rectum during APR, CAA, and AR when tumors were low in the
rectum is associated with low mortality, low morbidity, low local recurrence, and
good 5-year survival rates. Appropriate "tumor-specific" mesorectal excision
during AR when the tumor is high in the rectum is likewise consistent with a low
rate of local recurrence and good long-term survival. However, the overall
failure rate of 40% in stage III disease (which is independent of surgical
technique) means that surgical approaches alone are not sufficient to achieve
better long-term survival rates.
PMID- 9637544
TI - Transient human gene therapy: a novel cytokine regulatory strategy for
experimental pancreatitis.
AB - OBJECTIVE: The purpose of this study was to evaluate the ability to transfect a
murine pancreas with a human cytokine regulatory gene (interleukin-10 [IL-10])
and examine the duration of transgene expression, its effect on the normal
pancreas, and its antiinflammatory effect during acute pancreatitis. SUMMARY
BACKGROUND DATA: Interleukin-1beta and tumor necrosis factor-alpha are known
detrimental mediators during the progression of acute pancreatitis, and blockade
of either cytokine results in decreased severity of pancreatitis and improved
survival. Although gene therapy has been proposed as a method to deliver protein
based therapy during a number of conditions, no means of effectively transfecting
the pancreas without inducing injury has been developed. METHODS: A plasmid-human
IL-10 construct (pMP6-hIL-10) complexed with cationic liposomes was administered
by single intraperitoneal injection to healthy mice. Effective transfection
(reverse transcriptase-polymerase chain reaction for hIL-10 mRNA), transfected
cell type (in situ polymerase chain reaction for hIL-10 DNA), and the effect on
the normal pancreas were determined. Additional animals were transfected to
determine the effects of this regulatory gene on the severity of pancreatitis.
RESULTS: Nearly 80% of all pancreatic cells expressed human DNA that was
subsequently transcribed into mRNA through day 14. The transfection event had no
effect on amylase, lipase, or pancreatic histologic appearance. Successful
transfection could attenuate subsequently induced pancreatitis (all parameters p
< 0.05). CONCLUSIONS: Transient transfection of a human IL-10 gene can be
accomplished into all cell types of murine pancreata using a plasmid/ liposome
vector. The DNA is effectively transcribed into intact mRNA and does not cause
inflammation or acinar cell damage. Transfer of this cytokine regulatory gene
decreases the severity of pancreatitis, demonstrating a benefit of gene therapy
during this acute inflammatory process.
PMID- 9637545
TI - Periampullary adenocarcinoma: analysis of 5-year survivors.
AB - OBJECTIVE: This single-institution experience retrospectively reviews the
outcomes in a group of patients treated 5 or more years ago by
pancreaticoduodenectomy for periampullary adenocarcinoma. SUMMARY BACKGROUND
DATA: Controversy exists regarding the benefit of resection for periampullary
adenocarcinoma, particularly for pancreatic tumors. Many series report only
Kaplan-Meier actuarial 5-year survival rates. There are believed to be
discrepancies between the actuarial 5-year survival data and the actual 5-year
survival rates. METHODS: From April 1970 through May 1992, 242 patients underwent
pancreaticoduodenal resection for periampullary adenocarcinoma at The Johns
Hopkins Hospital. Follow-up was complete through May 1997. All pathology
specimens were reviewed and categorized. Actual 5-year survival rates were
calculated. The demographic, intraoperative, pathologic, and postoperative
features of patients surviving > or =5 years were compared with those of patients
who survived <5 years. RESULTS: Of the 242 patients with resected periampullary
adenocarcinoma, 149 (62%) were pancreatic primaries, 46 (19%) arose in the
ampulla, 30 (12%) were distal bile duct cancers, and 17 (7%) were duodenal
cancers. There was a 5.3% operative mortality rate during the 22 years of the
review, with a 2% operative mortality rate in the last 100 patients. There were
58 5-year survivors, 28 7-year survivors, and 7 10-year survivors. The tumor
specific 5-year actual survival rates were pancreatic 15%, ampullary 39%, distal
bile duct 27%, and duodenal 59%. When compared with patients who did not survive
5 years, the 5-year survivors had a significantly higher percentage of well
differentiated tumors (14% vs. 4%; p = 0.02) and higher incidences of negative
resection margins (98% vs. 73%, p < 0.0001) and negative nodal status (62% vs.
31%, p < 0.0001). The tumor-specific 10-year actuarial survival rates were
pancreatic 5%, ampullary 25%, distal bile duct 21%, and duodenal 59%.
CONCLUSIONS: Among patients with periampullary adenocarcinoma treated by
pancreaticoduodenectomy, those with duodenal adenocarcinoma are most likely to
survive long term. Five-year survival is less likely for patients with ampullary,
distal bile duct, and pancreatic primaries, in declining order. Resection margin
status, resected lymph node status, and degree of tumor differentiation also
significantly influence long-term outcome. Particularly for patients with
pancreatic adenocarcinoma, 5-year survival is not equated with cure, because many
patients die of recurrent disease >5 years after resection.
PMID- 9637546
TI - Reduction of hepatic ischemia/reperfusion injury by a soluble P-selectin
glycoprotein ligand-1.
AB - OBJECTIVE: The authors' goal was to determine the effects of specific binding and
blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1
(PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold
ischemia. The authors also sought to determine the effect of selectin blockade on
isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY
BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor
graft function after liver transplantation, which may profoundly influence early
graft function and late changes. It is hypothesized that I/R injury leads to the
upregulation of P-selectin, which is then rapidly translocated to endothelial
cell surfaces within 5 minutes of reperfusion of the liver, initiating steps
leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular
intima. Local production by leukocytes of interleukin-1, tumor necrosis factor
alpha, or both induces P-selectin expression on the endothelium and continues the
cascade of events, which increases cell adherence and infiltration of the organ.
METHODS: To examine directly the effects of selectins in a warm hepatic I/R
injury model, 100 microg of PSGL-1 or saline was given through the portal vein at
the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold
ischemia were assessed using an isolated perfused rat liver after 6 hours of 4
degrees C storage in University of Wisconsin (UW) solution, with or without the
instillation of PSGL-1 before the storage. To evaluate the effect of selectin
blockade on liver transplant survival, syngeneic orthotopic liver transplants
were performed between inbred male Sprague-Dawley rats after 24 hours of cold
ischemic storage in UW solution. A separate group of animals received two doses
of 100 microg of PSGL-1 through the portal vein before storage and before
reperfusion of the transplanted liver. Recipient survival was assessed at 7 days,
and the Kaplan-Meier product limit estimate method was used for univariate
calculations of time-dependent recipient survival events. RESULTS: In an in vivo
warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable
protection from I/R injury, as demonstrated by decreased transaminase release,
reduced histologic hepatocyte damage, and suppressed neutrophil infiltration,
versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1
reduced the degree of hepatocyte transaminase release, reduced neutrophil
infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only
controls). On reperfusion, livers treated with PSGL-1 demonstrated increased
portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In
addition, 90% of the rats receiving liver isografts stored in UW solution
supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted
syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins
play an important role in I/R injury of the liver. Early modulation of the
interaction between P-selectin and its ligand decreases hepatocyte injury,
neutrophil adhesion, and subsequent migration in both warm and cold rat liver
ischemia models. In addition, the use of PSGL-1 before ischemic storage and
before transplantation prevents hepatic injury, as documented by a significant
increase in liver isograft survival. These findings have important clinical
ramifications: early inhibition of alloantigen-independent mechanisms during the
I/R damage may influence both short- and long-term survival of liver allografts.
PMID- 9637547
TI - Improved clinical outcomes with liver transplantation for hepatitis B-induced
chronic liver failure using passive immunization.
AB - OBJECTIVE: The goals were to summarize the results of liver transplantation for
chronic hepatitis B disease (HBV) at the University of Virginia, correlate
pretransplant viral markers with posttransplant hepatitis B immunoglobulin (HBIg)
requirements, and identify the relation between viral protein in the liver and
clinical reinfection. SUMMARY BACKGROUND DATA: Liver transplantation is an
accepted treatment for end-stage liver disease from chronic HBV infection,
although lifelong antiviral treatment (with HBIg or antiviral agents) is still
necessary. Patients with evidence of active viral replication (detectable serum
HBV-DNA or e antigen) at the time of transplant have a higher rate of allograft
infection. Whether clinically stable patients receiving HBIg immunoprophylaxis
have detectable viral products in their grafts remains unknown. METHODS: Forty
four transplants performed for HBV disease at the University of Virginia since
March 1990 were reviewed. Most patients underwent aggressive passive
immunoprophylaxis with HBIg to maintain serum HBV surface antibody (HBsAb) levels
> or =500 IU/l for the first 6 months after the transplant, and > or =150 IU/l
thereafter. Patients had viral markers quantified, underwent pharmacokinetic
analysis of HBsAb levels to adjust dosing, and were biopsied routinely every 3 to
6 months and when indicated. RESULTS: Forty-four transplants were performed in 39
patients. Actual 1-year and 3-year graft survival was 95% and 81%, respectively,
and 1-year and 3-year patient survival was 98% and 96%, respectively. After the
adoption of indefinite HBIg prophylaxis, nine grafts became infected (all in
recipients positive for HBV e antigen). Three occurred within 8 weeks of
transplantation and were associated with a short HBsAb half-life and a wild-type
virus. Six occurred >8 months after the transplant, and most of these were
associated with viral mutation. Quantification of pretransplant markers was an
overall poor predictor of HBIg requirements after the transplant.
Immunohistochemistry demonstrated transient low-level expression of core protein
in the liver in 23% of patients without serum or clinical evidence of recurrent
hepatitis. CONCLUSIONS: An excellent outcome is possible after liver
transplantation for chronic HBV disease using HBIg dosed by pharmacokinetic
parameters. Currently, quantification of pretransplant serum markers of the HBV
antigen load does not predict the intensity of posttransplant treatment required
for good clinical outcomes. Because HBV is not eradicated from the patient, some
form of indefinite antiviral therapy continues to be warranted.
PMID- 9637548
TI - Microvascular changes explain the "two-hit" theory of multiple organ failure.
AB - OBJECTIVE: The objective was to determine intestinal microvascular endothelial
cell control after sequential hemorrhage and bacteremia. SUMMARY BACKGROUND DATA:
Sepsis that follows severe hemorrhagic shock often results in multiple system
organ failure (MSOF) and death. The sequential nature of this clinical scenario
has led to the idea of a "two-hit" theory for the development of MSOF, the
hallmark of which is peripheral vasodilation and acidosis. Acute bacteremia alone
results in persistent intestinal vasoconstriction and mucosal hypoperfusion.
Little experimental data exist to support the pathogenesis of vascular
dysregulation during sequential physiologic insults. We postulate that
hemorrhagic shock followed by bacteremia results in altered microvascular
endothelial cell control of dilation and blood flow. METHODS: Rats underwent
volume hemorrhage and resuscitation. A sham group underwent the vascular
cannulation without hemorrhage and resuscitation, and controls had no surgical
manipulation. After 24 and 72 hours, the small intestine microcirculation was
visualized by in vivo videomicroscopy. Mean arterial pressure, heart rate,
arteriolar diameters, and A1 flow by Doppler velocimetry were measured.
Endothelial-dependent dilator function was determined by the topical application
of acetylcholine (ACh). After 1 hour of Escherichia coil bacteremia, ACh dose
responses were again measured. Topical nitroprusside was then applied to assess
direct smooth muscle dilation (endothelial-independent dilator function) in all
groups. Vascular reactivity to ACh was compared among the groups. RESULTS: Acute
bacteremia, with or without prior hemorrhage, caused significant large-caliber A1
arteriolar constriction with a concomitant decrease in blood flow. This
constriction was blunted at 24 hours after hemorrhage but was restored to control
values by 72 hours. There was a reversal of the response to bacteremia in the
premucosal A3 vessels, with a marked dilation both at 24 and 72 hours. The
sequence of hemorrhage and E. coli resulted in a progressive enhanced reactivity
to the endothelial-dependent stimulus of ACh in the A3 vessels at 24 and 72
hours. Reactivity to endothelial-independent smooth muscle relaxation and
subsequent vessel dilation was similar for all groups. CONCLUSIONS: These data
indicate that there is altered endothelial control of the intestinal
microvasculature after hemorrhage in favor of enhanced dilator mechanisms in
premucosal vessels with enhanced constrictor forces in inflow vessels. This
enhanced dilator sensitivity is most evident in small premucosal vessels. This
experimental finding supports the premise that an initial pathophysiologic stress
alters the subsequent microvascular blood flow responses to systemic
inflammation. These changes in the intestinal microcirculation are in concert
with the "two-hit" theory for MSOF.
PMID- 9637549
TI - Diagnosis and initial management of blunt pancreatic trauma: guidelines from a
multiinstitutional review.
AB - OBJECTIVE: The authors' objective was to resolve the current controversies
surrounding the diagnosis and management of blunt pancreatic trauma (BPT).
SUMMARY BACKGROUND DATA: The diagnosis of BPT is notoriously difficult: serum
amylase has been claimed to be neither sensitive nor specific, and recent
anecdotal reports have suggested a role for computed tomography. The therapy of
BPT has been controversial, with some suggesting selective observation and others
advocating immediate exploration to prevent a delay-induced escalation in
morbidity and death. METHODS: The authors conducted a retrospective chart review
of documented BPT from six institutions, using a standardized binary data form
composed of 187 items and 237 data fields. RESULTS: A significant correlation
between pancreas-specific morbidity and injury to the main pancreatic duct (MPD)
was noted. Patients requiring delayed surgical intervention after an unsuccessful
period of observation demonstrated notably higher pancreas-specific mortality and
morbidity rates, principally because of the incidence of unrecognized injuries to
the MPD. Although detection of MPD injuries by computed tomography was no better
than flipping a coin, endoscopic pancreatography was accurate in each of the five
cases in which it was used. CONCLUSIONS: The principal cause of pancreas-specific
morbidity after BPT is injury to the MPD. Parenchymal pancreatic injuries not
involving the ductal system rarely result in pancreas-specific morbidity or
death. Delay in recognizing MPD injury leads to increased mortality and morbidity
rates. CT is unreliable in diagnosing MPD injury and should not be used to guide
therapy. Initial selection of patients with isolated BPT for observation or
surgery can be based on the determination of MPD integrity.
PMID- 9637550
TI - Pancreatic necrosis: results of necrosectomy, packing, and ultimate closure over
drains.
AB - OBJECTIVE: The treatment of pancreatic necrosis at a tertiary referral center was
reviewed to effect better patient outcome. SUMMARY BACKGROUND DATA: Pancreatic
necrosis is a devastating disease that leads to death in 10% to 50% of cases.
Infected necrosis is particularly deadly because 80% of deaths from necrosis are
due to infection or its complications. Therapeutic strategies center on
aggressive support of organ systems and prevention and treatment of infectious
complications. METHODS: Records of all patients who underwent pancreatic
necrosectomy from 1990 to 1996 at Emory University Hospital were reviewed.
Patients with infected necrosis were debrided as soon as the diagnosis was made.
Reoperation for completion necrosectomy with ultimate closure over lavage
catheters was performed as necessary. RESULTS: Of the 244 patients admitted with
acute pancreatitis in the study period, 50 underwent pancreatic debridement. The
mean age was 52 years, and 74% of patients were transferred from other
institutions. Eighty-four percent of patients had infected necrosis, and all
patients underwent sequential debridement with eventual closure over drains.
Organ failure occurred in 72% of cases, and the overall mortality rate was 12%.
The mean length of stay was 54 days. CONCLUSIONS: The management of pancreatic
necrosis demands the allocation of extensive resources. An aggressive operative
strategy of multiple debridements with ultimate closure over drains can lead to a
low mortality rate in patients with this complex disease, but the determination
of when to explore patients with sterile necrosis remains difficult.
PMID- 9637551
TI - Operative treatment of tertiary hyperparathyroidism: a single-center experience.
AB - OBJECTIVE: To review the experience with the operative treatment of tertiary
hyperparathyroidism (TH) from a single renal transplant center. SUMMARY
BACKGROUND DATA: Most patients with chronic renal failure show evidence of
secondary hyperparathyroidism by the time maintenance hemodialysis begins.
Persistent secondary hyperparathyroidism (i.e., TH) requiring surgical
intervention is uncommon in the authors' experience. METHODS: Charts of patients
who underwent parathyroidectomy for TH were reviewed retrospectively. Information
obtained included demographics, laboratory data, symptoms, operative procedure
(including morbidity and mortality rates), and pathology. Comparisons of
demographic data and allograft survival were made between the transplant
population as a whole and a matched cohort group of patients. RESULTS: Thirty
eight patients from 4344 renal transplant procedures during a 29-year period
required parathyroidectomy for TH. All patients had hypercalcemia; 20 were
asymptomatic and 18 had varying symptoms. Mean time from renal transplantation to
parathyroidectomy was 997 +/- 184 days, with a mean preoperative calcium level of
12.2 +/- 0.14 mg/dl. Total parathyroidectomy with parathyroid autograft was
performed in 26 of 34 primary procedures. There were no deaths. The operative
morbidity rate was 6% (wound separation and vocal cord hemiparesis, one each).
Pathology was reported in all patients and recently reviewed in 28 patients.
Twenty-four had diffuse hyperplasia and nine had nodular hyperplasia; one had an
adenoma. Parathyroid glands diagnosed as nodular hyperplasia were significantly
larger by total mass than those with diffuse hyperplasia. Comparison of allograft
survival between the study group and a matched cohort group of patients revealed
no difference in long-term graft survival. CONCLUSIONS: Operative intervention is
recommended in patients with an asymptomatic increase in serum calcium to >12.0
mg/dl persisting for >1 year after the transplant, acute hypercalcemia (calcium
>12.5 mg/dl) in the immediate posttransplant period, and symptomatic
hypercalcemia.
PMID- 9637552
TI - Effective long-term palliation of symptomatic, incurable metastatic medullary
thyroid cancer by operative resection.
AB - OBJECTIVE: To evaluate the short- and long-term consequences of palliative
reresection of specific symptomatic lesions in patients with widely disseminated
(incurable) medullary thyroid cancer (MTC). SUMMARY BACKGROUND DATA: Although
reoperative neck microdissections can normalize calcitonin levels in patients
with metastatic MTC confined to regional lymph nodes, there is no curative
therapy for widely metastatic disease. However, these patients frequently have
prolonged survival, but often with debilitating symptoms. METHODS: Between
October 1981 and January 1997, 16 patients (mean age, 46 +/- 3 years; 10/16
female) underwent 21 palliative reoperations for unresectable MTC at the Johns
Hopkins Hospital. All patients had significant symptom(s) or impending compromise
of vital structures by a discrete lesion and had unequivocal preoperative
evidence of a total disease burden that was unresectable. RESULTS: The mean
interval from initial thyroidectomy to palliative surgery was 5.8 +/- 1.5 years.
All patients had significant tumor burdens as evidenced by preoperative
calcitonin values ranging from 900 to 222,500 pg/mL (nL < or = 17 pg/mL). The
palliative operations consisted of reoperative neck dissection/mass excision
(11), mediastinal mass resection (4), esophagectomy (1), liver trisegmentectomy
(1), sigmoidectomy (1), bilateral simple mastectomies (1), pituitary resection
(1), and subcutaneous mass excisions (1). All but two of the operative specimens
contained MTC. There was no perioperative mortality. The long-term morbidity rate
was limited to one recurrent laryngeal nerve injury. All patients had initial
relief of the index symptom(s) after the palliative surgery, followed by a median
actuarial symptom-free survival rate of 8.2 years. CONCLUSIONS: Patients with
widely metastatic MTC often live for years, but many develop symptoms secondary
to tumor persistence or progression. Judicious palliative, reoperative resection
of discrete, symptomatic lesions can provide significant long-term relief of
symptoms with minimal operative mortality and morbidity. In selected patients
with metastatic MTC lesions causing significant symptoms or physical compromise,
palliative reoperative resection should be considered despite the presence of
widespread incurable metastatic disease.
PMID- 9637553
TI - Cystadenomas of the pancreas: is enucleation an adequate operation?
AB - OBJECTIVE: The objective was to determine whether surgical enucleation of
mucinous cystadenoma of the pancreas is a safe and adequate operation. SUMMARY
BACKGROUND DATA: Mucinous cystadenomas of the pancreas are premalignant cystic
lesions. Resection is the preferred treatment but often requires a
pancreatoduodenectomy or a distal pancreatectomy with or without a splenectomy.
Although these procedures can now be performed with a low mortality rate,
substantial morbidity still occurs, especially in patients who have an otherwise
normal pancreas. METHODS: Between January 1990 and June 1997, 36 mucinous
cystadenomas of the pancreas were resected at The Johns Hopkins Hospital. Most of
these patients underwent pancreatoduodenectomy or distal pancreatectomy. However,
10 patients (28%) underwent enucleation of their cystic tumor. These 10 patients
had a mean age of 63 years, and 6 were men. The cystic lesion was demonstrated by
computed tomography in all patients. Enucleation of the cyst was performed in
each patient, and four underwent another concomitant abdominal procedure. These
10 patients were followed with periodic computed tomographic scans and clinical
examinations. RESULTS: Enucleation took less time and was associated with less
blood loss than resection. Pancreatic fistulas occurred more frequently after
enucleation, but the incidence of major complications was similar between the two
groups. Follow-up after enucleation averaged 43 months, and none of the patients
developed late sequelae or recurrence. CONCLUSIONS: This experience suggests that
enucleation of mucinous cystadenomas of the pancreas can be performed safely and
that the recurrence rate is low after this procedure. The authors conclude that
enucleation is an adequate procedure for benign cystic neoplasms of the pancreas.
PMID- 9637554
TI - Acute pancreatitis induces cytokine production in endotoxin-resistant mice.
AB - OBJECTIVE: The purpose of this study was to determine whether pathologic
progression and cytokine responses in acute pancreatitis (AP) are altered in the
absence of endotoxemia. SUMMARY BACKGROUND DATA: Previous studies have
demonstrated that AP is characterized by rapid production and release of
inflammatory cytokines, which play a major role in the local pancreatic and
systemic complications of this disease. Infection and endotoxemia have been
implicated as a major source of morbidity and death in AP and as possible stimuli
for the overwhelming cytokine response seen in this disease. METHODS: AP was
induced by a choline-deficient and ethionine-supplemented diet for 4 days in
normal C57BL/6J mice (controls, n = 23) and in CD14 knockout mice (CD14KO, n =
23), which cannot produce circulating cytokines in response to endotoxin. Control
and endotoxin-resistant mice were killed at time 0, then at 24, 48, 72, and 96
hours after the start of the diet. At each time point serum was collected for
amylase, glucose, and cytokine measurements (tumor necrosis factor-alpha
[TNFalpha] and interleukin-1beta [IL1beta]), and the pancreas was removed for
histologic examination. TNFalpha was measured with a bioassay using WEHI-2F cells
and IL1beta with a bioassay using D10.G4.1 cells. RESULTS: CD14KO mice developed
biochemical manifestations of AP with alterations in amylase levels,
hypoglycemia, weight loss, and histologic changes of pancreatitis similar to the
pattern seen in control mice. TNFalpha and IL1beta production had similar
kinetics in both groups, with significant peak TNFalpha serum levels at 72 hours
and a progressive rise of IL1beta levels throughout the study period. Histologic
changes appeared earlier and were more pronounced in the control versus the
CD14KO mice. However, the mortality rate was identical (20% at 96 hours) for both
groups. CONCLUSIONS: These results demonstrate that the progression of AP, the
cytokine response associated with the disease, and early death are independent of
endotoxin action. These findings, which suggest that an uncharacterized stimulus
is responsible for triggering the cytokine cascade in this disease, may have
significant implications for the management of patients with AP.
PMID- 9637555
TI - Total thyroidectomy does not enhance disease control or survival even in high
risk patients with differentiated thyroid cancer.
AB - SUMMARY BACKGROUND DATA: The extent of primary thyroidectomy for differentiated
thyroid cancer is controversial. There are strong proponents for total
thyroidectomy based on its presumed and theoretical disease control benefits. In
contrast, there are equally strong advocates of less aggressive thyroidectomy
with its lower hazard of parathyroid and recurrent nerve injury. The authors have
addressed whether total thyroidectomy has a survival benefit justifying its use
in patients with high-risk primary cancer. The major risk factors include age and
the following the pathologic determinants follicular histology, vascular
invasion, and extracapsular extension. MATERIALS AND METHODS: The clinical
pathologic, therapeutic, prognostic, and outcome data were reviewed in 347
patients with well-differentiated thyroid cancer. Seventy-five percent were
women, 216 patients were in the younger age group (low-risk) (21-50 years), 103
were in the intermediate-risk group (51-70 years), and 28 were in the high-risk
group (>70 years). Included in the high-risk pathologic category were 158
patients who had follicular histology (55), extracapsular extension (107), or
vascular invasion (119). Total thyroidectomy was performed in 56 patients, near
or subtotal thyroidectomy in 47 patients and lobectomy in 55 patients. The 10
year disease specific survival in the overall patient group was 82% in patients
with total thyroidectomy, 78% in patients with subtotal thyroidectomy, and 89% in
patients with lobectomy (p = 0.30). There was no significant survival difference
according to extent of thyroidectomy in the intermediate or high-risk groups
either by age or in patients who had high-risk pathologic feature. CONCLUSIONS:
Total thyroidectomy in high-risk patients with differentiated thyroid cancer
(containing follicular histology, vascular invasion, or extracapsular extension)
showed no benefit over partial thyroidectomy. This suggests that the general use
of total thyroidectomy is not indicated, except in highly selected patients.
PMID- 9637557
TI - Image-guided core-needle breast biopsy is an accurate technique to evaluate
patients with nonpalpable imaging abnormalities.
AB - OBJECTIVE: The goal was to evaluate one institution's experience with image
guided core-needle breast biopsy (IGCNBB) and compare the pathologic results with
wire-localized excisional breast biopsy (WLEBB) for patients with positive cores
and the mammographic surveillance results for patients with negative cores.
SUMMARY BACKGROUND DATA: IGCNBB is becoming a popular, minimally invasive
alternative to WLEBB in the evaluation of patients with nonpalpable
abnormalities. METHODS: This study includes all patients with nonpalpable breast
imaging abnormalities evaluated by IGCNBB from July 1993 to February 1997.
Patients with positive cores (atypical hyperplasia, carcinoma in situ, or
invasive carcinoma) were evaluated by WLEBB. Patients with negative cores (benign
histology) were followed with a standard mammographic protocol. IGCNBB results
were compared with WLEBB results to determine the sensitivity and specificity for
each IGCNBB pathologic diagnosis. RESULTS: Of 1440 IGCNBBs performed during the
study period, 1106 were classified as benign, and during surveillance follow-up
only a single patient was demonstrated to have a carcinoma in the index part of
the breast evaluated by IGCNBB (97.3% sensitivity, 99.7% specificity). IGCNBB
demonstrated atypical hyperplasia in 72 patients, 5 of whom refused WLEBB. The
remaining 67 patients were evaluated by WLEBB: nonmalignant findings were found
in 31, carcinoma in situ was found in 25, and invasive carcinoma was found in 11
(100% sensitivity, 88.8% specificity). IGCNBB demonstrated carcinoma in situ in
84 patients; WLEBB confirmed carcinoma in situ in 54 and invasive carcinoma in 30
(65.4% sensitivity, 97.7% specificity). IGCNBB demonstrated invasive carcinoma in
178 patients. Three were lost to follow-up. On WLEBB, 173 of the remaining 175
had invasive carcinoma; the other 2 patients had carcinoma in situ (80.8%
sensitivity, 99.8% specificity). CONCLUSIONS: An IGCNBB that demonstrates
atypical hyperplasia or carcinoma in situ requires WLEBB to define the extent of
breast pathology. Mammographic surveillance for a patient with a benign IGCNBB is
supported by nearly 100% specificity. An IGCNBB diagnosis of invasive carcinoma
is also associated with nearly 100% specificity; therefore, these patients can
have definitive surgical therapy, including axillary dissection or mastectomy,
without waiting for the pathologic results of a WLEBB. Based on the authors'
findings, IGCNBB can safely replace WLEBB in evaluating patients with nonpalpable
breast abnormalities.
PMID- 9637556
TI - Effects of 5-azacytidine and butyrate on differentiation and apoptosis of hepatic
cancer cell lines.
AB - OBJECTIVE: To determine the cellular effects of 5-azacytidine (5-azaC) and sodium
butyrate on two human liver cancers, HepG2 and Hep3B. SUMMARY BACKGROUND DATA:
Primary liver cancer is a significant health problem; treatment options are
limited and prognosis is poor. Recent studies have focused on the role that
programmed cell death (i.e., apoptosis) plays in both normal and neoplastic
growth: certain genes can either suppress (e.g., Bcl-2, Bcl-xL) or promote (e.g.,
Bik, Bax, Bak) apoptosis. The identification of novel agents targeted to specific
molecular pathways may be beneficial in the treatment of this disease. METHODS:
Human liver cancer cell lines HepG2 and Hep3B were treated with 5-azaC alone,
butyrate alone, or 5-azaC and butyrate. Morphologic and proliferative changes
were assessed by light microscopy and 5-bromo-2'-deoxyuridine staining; flow
cytometry was used to determine cell cycle characteristics. Apoptosis was
assessed by DNA laddering and the in situ apoptosis detection assay using the TdT
mediated dUTP nick end labeling method. In addition, total RNA and protein were
analyzed by ribonuclease protection and Western blot, respectively, to assess
changes in the expression of apoptosis-related genes. RESULTS: Treatment with
either 5-azaC or butyrate inhibited cell growth and induced apoptosis in both
HepG2 and Hep3B cells; the combination of 5-azaC and butyrate was not more
effective than either agent alone. 5-azaC alone resulted in a more differentiated
appearing morphology and G2 cell cycle arrest in both cell lines. Treatment with
5-azaC or butyrate affected the expression levels of proteins of the Bcl-2
family. CONCLUSIONS: Both 5-azaC and butyrate induced apoptosis in the HepG2 and
Hep3B liver cancer cells; 5-azaC treatment alone produced G2 arrest in both cell
lines. Proteins of the Bcl-2 family may play a role in the cellular changes that
occur with treatment, but further studies are required to define this potential
role. Products of the apoptotic pathway may prove to be useful therapeutic
targets in the treatment of hepatic cancers.
PMID- 9637558
TI - Orthodontic Centers of America letter brings comments.
PMID- 9637559
TI - Long-term concerns.
PMID- 9637560
TI - Early treatment is a very strong tendency between the orthodontists and
dentofacial orthopedists.
PMID- 9637561
TI - A longitudinal laser fluorescence study of white spot lesions in orthodontic
patients.
AB - Orthodontic treatment with fixed appliances increases the caries risk in young
persons. The aim of this study was to apply a new caries diagnostic method,
quantitative laser fluorescence, for longitudinal in vivo quantification of
changes in incipient enamel lesions related to fixed orthodontic appliances.
Seven young patients with active caries lesions disclosed at removal of the
orthodontic brackets and bands were enrolled in the study. Caries preventive
measures were intensified, including dietary advice, oral hygiene instructions,
and the regular use of a fluoride dentifrice. The caries lesions were monitored
with the quantitative laser fluorescence method after removal of the brackets and
once a month thereafter. For each lesion, three quantities were measured: lesion
area (mm2), mean fluorescence loss (%) over the lesion, and maximum loss of
fluorescence (%) in the lesion. During a 1-year follow-up period, the areas of
the lesions decreased and the enamel fluorescence lost was partly regained
indicating that a remineralization process had occurred. It was concluded that
quantitative laser fluorescence seems suitable for in vivo monitoring of mineral
changes in incipient enamel lesions, and useful for the evaluation of preventive
measures in caries prone persons, such as orthodontic patients.
PMID- 9637562
TI - Nasal obstruction and facial growth: the strength of evidence for clinical
assumptions.
AB - The orthodontic relevance of nasorespiratory obstruction and its effect on facial
growth continues to be debated after almost a century of controversy. The
continuing interest in nasal obstruction is fueled by strong convictions, weak
evidence, and the prevailing uncertainty of cause and effect relationships that
exist. The essence of any debate is to provide opposing evidence from which a
majority vote is obtained. Political issues may be appropriately resolved by such
means as a majority vote. Scientific issues, however, can only be resolved by
data and appropriately structured hypotheses put to the test. One of the problems
in debating nasorespiratory obstruction and facial growth is the inability to
provide unequivocal answers to such issues as: How much nasal obstruction is
clinically significant? At what age is the onset critical and for how long does
it have to exist before an effect on facial growth can be expected? To provide
unequivocal answers, clinical studies need to be designed to identify and
quantify the degree of nasorespiratory obstruction and compare individuals for
any clinically relevant differences. The purpose of this article is to review the
available evidence. If both data and untested popular beliefs are subjected to
the same rigorous criteria, indications for the orthodontic management of
patients with nasorespiratory obstruction may gain a more rational approach to
treatment recommendations.
PMID- 9637563
TI - Maxillary protraction: treatment and posttreatment effects.
AB - This study evaluated the treatment response and posttreatment follow-up of
children with Class III malocclusions treated with palatal expansion and reverse
pull face mask to the maxilla. The sample included 22 white children, 9 boys and
13 girls. Treatment began at a mean age of 9.8 years (range 5.6 to 13.3 years)
and lasted 0.7 years (range 0.3 to 1.3 years). With a protraction force of 600 to
800 gm, the patients were treated until a 2 mm positive overjet had been
attained. Radiographs were taken before treatment (T1), immediately after face
mask treatment (T2), and 1.4 years after treatment (T3). An age and sex matched
sample of untreated white schoolchildren served as normal controls. The results
showed that the anterior maxilla was protracted forward 1.6 mm per year more than
normal. The posterior maxilla dropped inferiorly more than the anterior maxilla.
The mandible was rotated downward and backward, while the lower incisors were
uprighted. The effects on the mandible were attributed to a significant chincup
effect exerted by the face mask. After treatment, the maxilla relapsed relatively
backward in the anterior and upward in the posterior, negating some of the
treatment results. The mandible resumed a normal growth direction, and the lower
incisors flared more than normal.
PMID- 9637564
TI - In vitro study of 24-hour and 30-day shear bond strengths of three resin-glass
ionomer cements used to bond orthodontic brackets.
AB - Interest in using composite resin-glass ionomer hybrid cements as orthodontic
bracket adhesives has grown because of their potential for fluoride release. The
purpose of this pilot study was to compare shear bond strengths of three resin
glass ionomer cements (Advance, Fuji Duet, Fuji Ortho LC) used as bracket
adhesives with a composite resin 24 hours and 30 days after bonding. The amount
of adhesive remaining on the debonded enamel surface was scored for each
adhesive. Mesh-backed stainless-steel brackets were bonded to 100 extracted human
premolars, which were stored in artificial saliva at 37 degrees C until being
tested to failure in a testing machine. The hybrid cements, with one exception,
had bond strengths similar to those of the composite resin at 24 hours and 30
days. Fuji Ortho LC had significantly lower bond strengths (ANOVA p < or = 0.05)
than the other adhesives at 24 hours and 30 days when it was bonded to unetched,
water-moistened enamel. Adhesive-remnant scores were similar for all cements,
except for cement Fuji Ortho LC when it was bonded to unetched enamel. The resin
glass ionomer cements we tested appear to have bond strengths suitable for
routine use as orthodontic bracket-bonding adhesives.
PMID- 9637565
TI - Unexpected temporomandibular joint findings during fixed appliance therapy.
AB - Six hundred consecutively debonded patients were retrospectively examined for the
development of any temporomandibular joint signs or symptoms that developed
during orthopedic/orthodontic treatment. Sixteen (2.6%) patients were found to
have developed unexpected temporomandibular joint findings during treatment.
Considering such a small sample, no conclusive results could be found, but
several tendencies seemed to be apparent. Those types of patients who seemed to
be most predisposed to developing temporomandibular joint problems included
female Class II patients with excessive overjet and overbite and moderate to
severe crowding of the lower arch. Ninety-three percent of the patients
experienced posterior net condylar change in spite of using several different
treatment mechanics. The types of treatments used included FJO appliances,
headgear, Class II and Class III elastics, no elastics of any kind, extraction
and nonextraction. This small study seems to suggest that temporomandibular joint
signs and symptoms are changing, inconsistent, and ephemeral in many orthodontic
patients regardless of the treatment mechanics.
PMID- 9637566
TI - A formula for the displacement of an arch wire when subjected to a second-order
couple.
AB - A new formula, expressing the local angular displacement of an orthodontic beam
when subjected to a second-order couple applied at midspan, has been developed
and analyzed. The computed displacements were compared with the results of ex
vivo testing. There was good agreement between the results from the theoretical
evaluation and the bench testing. Second-order activation of an orthodontic beam
can be described in four sequential phases. The initial displacement is
influenced by the second-order clearance between bracket-slot and wire as well as
the relationship between the bracket-slot width and interbracket distance. During
phase II there is a nonlinear relationship between applied couple and rotational
displacement. Within phases three and four displacement is linearly related to
the interbracket distance, provided the relationship between the bracket-slot
width and interbracket distance remains constant. For a given tooth size, the
second-order beam stiffness is exponentially related to bracket width. The
experiments also show that even small deflections of thin stainless steel wires
can lead to second-order couples of large magnitudes when using a clinically
relevant interbracket distance. Consequently, it is important that the
orthodontist evaluates his or her choice of bracket width and arch wire stiffness
in each clinical case in order to avoid supra-physiologic force levels.
PMID- 9637567
TI - Functional treatment of condylar fractures in adult patients.
AB - Functional treatment of condylar fractures in adult patients usually follows the
closed reduction/maxillomandibular fixation approach. Some of the problems
arising when functional appliances (i.e., activator) are used have been
identified and presented here, especially in patients where fractured parts are
dispositioned/dislocated. The cause is discussed and a different functional
approach is proposed that yields good results.
PMID- 9637568
TI - Compliance with infection-control procedures among Illinois orthodontists.
AB - The authors of previous studies have reported an increasing percentage of
orthodontists complying with infection-control procedures in their offices, yet
compliance was found to be less than ideal. In this study we surveyed Illinois
orthodontists to evaluate their compliance with the infection-control guidelines
established by the American Dental Association and the Centers for Disease
Control and Prevention. This study is an addition to a small number of studies in
the field of orthodontics on infection-control procedures. The study population
was taken from the World Directory of Orthodontists, which contains 374 listings
for the state of Illinois. Responses were received from 140 orthodontists, for a
response rate of 37%. Thirty-two percent of the responding orthodontists stated
that they always wear masks; 13% said they never do. Almost 97% of the
orthodontists said they always wear gloves, and no orthodontist reported never
wearing gloves. Nearly 64% of the orthodontists reported always using eyewear,
and 34% said they wear gowns, whereas only 5% do not wear eye protection and 35%
never wear gowns. With regard to instruments and pliers, most of the
orthodontists reported using dry-heat ovens (72% and 80%, respectively), whereas
nearly 58% said they use chemical disinfection to some extent on instruments and
39% said they use chemical disinfection on pliers. Only 51% of the orthodontists
surveyed in our study reported using a steam autoclave to sterilize handpieces,
whereas 27% said they use dry-heat ovens, 11% reported using chemical vapor, and
37% said they use chemical disinfection. In conclusion, compliance with infection
control procedures among orthodontists has improved from recent studies but is
still less than full compliance.
PMID- 9637569
TI - Nickel hypersensitivity reaction before, during, and after orthodontic therapy.
AB - Nickel is a strong biological sensitizer and consequently may induce a delayed
hypersensitivity reaction (type IV immune response). Because nickel is a
component of the majority of the orthodontic alloys, the objectives of this cross
sectional study were to determine the prevalence of nickel hypersensitivity
reaction before, during, and after orthodontic therapy with conventional
stainless steel brackets and wires; to evidence the induction of this reaction by
the orthodontic appliances; and to characterize the nickel hypersensitive
persons. Nickel patch tests and a questionnaire were used to evaluate the
hypersensitivity to this metal. The total sample consisted of 170 patients, 105
females and 65 males, from the orthodontic department at Bauru Dental School,
University of Sao Paulo. They were divided into three groups as follows: A (n =
60), patients before the beginning of orthodontic therapy; B (n = 66), patients
currently undergoing orthodontic treatment, and C (n = 44), patients who had
undergone orthodontic treatment previously. The chi-square test (chi2) showed an
allergic reaction in 28.3% of the total sample with 23% female and 5.3% male.
This indicated a gender difference (chi2 = 10.75, p < 0.001). There was a
positive association between nickel hypersensitivity and previous personal
allergic history to metals (chi2 = 34.88, p < 0.0001) as well as with the daily
use of metal objects (chi2 = 11.95, p < 0.0005). There was no statistically
significant difference in the prevalence of contact dermatitis among the three
groups (chi2 = 0.39, p = 0.848). This suggests that orthodontic therapy with
conventional stainless steel appliances does not initiate or aggravate a nickel
hypersensitivity reaction.
PMID- 9637570
TI - Mandibular changes in persons with untreated and treated Class II division 1
malocclusion.
AB - The growth potential of individuals with Class II malocclusions is of interest to
the practicing orthodontist because such malocclusions constitute a significant
percentage of cases. The purpose of this study was to evaluate on cross-sectional
and longitudinal bases the changes in mandibular length and relationship and
maxillary-mandibular relationships in untreated Class II subjects from deciduous
to permanent dentition and also to evaluate the effects of orthodontic treatment,
with and without the extraction of first premolars, on these relationships. Class
II samples were compared with matched normal, untreated individuals. The Class II
division 1 (Class II/1) untreated sample comprised 30 subjects, 15 males and 15
females. Each subject had a complete set of data at three stages of dental
development-namely, Stage I, after the completion of eruption of the deciduous
dentition; Stage II, at the time when the permanent first molars and most of the
incisors have erupted (i.e., in mixed dentition); and Stage III, at the
completion of eruption of the permanent dentition, excluding third molars. The
Class II treated sample comprised 44 subjects (21 males, 23 females) treated with
four first-premolar extractions and 47 subjects (20 males, 27 females) treated
without extraction. Treatment was accomplished with the use of an edgewise
appliance, appropriate extraoral traction, and Class II elastics. The extraction
decision was based mainly on the presence of crowding and profile consideration.
Records on 35 normal subjects (20 males, 15 females) were available from the Iowa
Longitudinal Facial Growth Study. Cephalograms for the normal individuals were
matched to the corresponding ages of the Class II cases. With regard to these
findings, few consistent differences were noted between the untreated Class II/1
and normal subjects on cross-sectional comparisons. The differences in mandibular
length and position were more evident in the early stages of development than at
later stages. Longitudinal comparisons of growth profiles indicated that the
growth trends were essentially similar between the untreated Class II/1 and
normal subjects in the various parameters compared. The comparisons of growth
magnitude indicated the presence of greater skeletal facial convexity in the
untreated Class II/1 subjects, accompanied by a tendency for a more retruded
mandible. Initial comparisons between the Class II/1 treated groups and normal
subjects indicated that the Class II/1 malocclusions were associated with a
larger overjet, deeper overbite, and greater ANB angle. After a 5-year treatment
and observation period, an overall "normalization" in the mandibular and
maxillary-mandibular skeletal relationships was noted in the treated Class II/1
subjects in both the extraction and the nonextraction groups compared with normal
subjects. The changes were more pronounced in the extraction group.
PMID- 9637571
TI - Soft tissue adaptability to hard tissues in facial profiles.
AB - The purpose of this study was to investigate soft tissue adaptability to hard
tissue. A canonical correlation analysis was performed in an attempt to assess
the relationships between hard tissue structure and soft tissue profile in the
static state. For the dynamic study, multiple-regression analysis was performed
to identify the changes of soft tissue profiles associated with the retraction of
upper and lower incisors. The samples comprised lateral cephalograms from 297
Japanese women for the static canonical correlation analysis and 32 sets of
lateral cephalograms of pre- and posttreatment adult orthodontic patients for the
dynamic multiple-regression analysis. In the static state, the vertical dimension
of lower facial height and the position of the lower incisors were associated
with the thickness of the upper-lip vermilion and soft tissue B, and the
horizontal relationships between upper- and lower-jaw positions were associated
with the thickness of upper lips and of pogonion (soft tissue chin). In the
dynamic state, the results indicated that the changes of stomion and lower lip
could be predicted and strongly reflected the changes of the hard tissue. On the
contrary, the change of the upper lip showed a weaker association with the hard
tissue changes. Predictions of chin form described by the soft tissue B and soft
tissue pogonion were less accurate than estimates of upper- and lower-lip form.
Chin form was influenced by the hard tissue structures such as ANB angle and
lower-facial height rather than by changes in lower- and upper-incisor
retraction.
PMID- 9637572
TI - Six blind men and the elephant: a paradox story on relapse.
PMID- 9637573
TI - Litigation, legislation, and ethics. Defining the standard of care.
PMID- 9637574
TI - Role of the thymus in pediatric HIV-1 infection.
AB - Several lines of evidence suggest that HIV-1 is present in the thymus during HIV
1 infection. Precursors to mature CD4+ T lymphocytes develop in the thymus, which
suggests that thymic infection may play a role in the CD4+ T-cell decline
observed during the course of pediatric HIV-1 infection. We illustrate, through
mathematical modeling, the potential effects of thymic infection on the course of
pediatric AIDS disease progression. We find that infection in the thymus not only
can supplement peripheral infection but can help explain the faster progression
in pediatric cases, as well as the early and high viral burden.
PMID- 9637575
TI - Chemokine receptor CCR2b 64I polymorphism and its relation to CD4 T-cell counts
and disease progression in a Danish cohort of HIV-infected individuals.
Copenhagen AIDS cohort.
AB - We have investigated the role of the recently described mutation in CCR2b named
64I in relation to HIV resistance, CD4 T-cell counts, and disease progression in
Danish individuals by polymerase chain reaction (PCR)-based methods as well as
sequenced full-length CXCR4 and CCR5 genes from HIV-infected long-term
nonprogressors for possible mutations. In total, 215 Danish individuals were
analyzed for 64I allele frequency; disease progression was followed in 105 HIV-1
positive homosexual Danish men from their first known positive HIV-1 test result
and up to 11 years. In 87 individuals, the CD4 T-cell count was monitored
closely. We found no significant difference in 64I allele frequency between HIV-1
seropositive persons (0.08), high-risk HIV-1-seronegative persons (0.11), and
blood donors (0.06). No significant difference was observed in annual CD4 T-cell
decline, CD4 T-cell counts at the time of AIDS, in AIDS-free survival as well as
survival with AIDS, between 64I allele carriers and wild-type individuals. Among
9 long-term nonprogressors, 2 carried the 64I allele, while none of 9 fast
progressors carried the 64I allele. However, this was not significantly different
(p=.47). Long-term nonprogression could not be explained by CXCR4 polymorphism or
other polymorphisms in the CCR5 gene than the CCR5delta32 allele. Furthermore, we
were not able to detect any significant independent effect of the 64I allele on
development to AIDS, overall survival, and annual CD4 T-cell decline in this
cohort.
PMID- 9637576
TI - Adherence to antiretroviral and pneumocystis prophylaxis in HIV disease.
AB - BACKGROUND: Medication nonadherence in the treatment of chronic diseases
compromises the effectiveness of therapy. Little information is available about
the extent of medication adherence or determinants of medication adherence in HIV
disease, an issue of increasing importance in this new therapeutic era of
combination antiretroviral therapy. METHODS: We studied 244 HIV-infected Medicaid
insured patients attending an HIV hospital-based clinic regarding the extent of
and predictors of adherence to antiretroviral therapy and Pneumocystis carinii
pneumonia (PCP) prophylaxis. Patients were asked to report medications being
taken, patterns of use, and knowledge and attitudes about HIV therapies. Medical
record report of type, dose, and frequency of medication was compared with self
report using the kappa statistic. Urine sulfamethoxazole assay was obtained from
patients prescribed sulfamethoxazole-trimethoprim. RESULTS: Among patients
prescribed antiretroviral therapy, 60% reported > or = 80% adherence in the
previous 7 days; 49% reported > or = 80% adherence with PCP prophylaxis in the
previous seven days. Seventy-nine percent of patients who reported taking daily
sulfamethoxazole-trimethoprim had detectable urinary sulfamethoxazole. In
multivariate analysis, > or = 80% adherence to antiretroviral therapy was
associated with taking medication < or = twice a day (odds ratio [OR]=1.44; 95%
confidence interval [CI], 1.01, 1.96), being likely to take medication when not
at home, (OR=1.41; 95% CI, 1.04, 2.00) and patients' belief in their ability to
adhere to therapy (OR=1.57; 95% CI, 1.13, 2.17). For PCP prophylaxis, > or = 80%
adherence was associated with presence of family (OR=2.39; 95% CI, 1.01, 5.63)
and patients' belief in their ability to adhere to therapy (OR=2.87; 95% CI, 1.44
1.78). Sociodemographic characteristics and belief in the efficacy of medications
were not associated with adherence. CONCLUSIONS: A relatively low level of
adherence to antiretroviral therapy and PCP prophylactic regimens was found.
Although our results are principally from patients receiving antiretroviral
monotherapy, these findings may have important implications for patients
receiving highly active antiretroviral therapy (HAART). Decreasing the complexity
of antiretroviral regimens, and working with patients to modify identified
barriers to adherence may improve effectiveness of medications and prolong
survival.
PMID- 9637577
TI - Maternal cell-free viremia in the natural history of perinatal HIV-1
transmission: a meta-analysis.
AB - We performed a meta-analysis of the predictive value of maternal cell-free viral
load in vertical HIV-1 transmission, including 9 cohorts with 1115 mother-infant
pairs (696 untreated and 419 treated women). The pooled rate of transmission in
untreated women was 21.3% (95% confidence interval [CI], 18.3%-24.5%). The rates
of transmission for untreated women in the <1000 copies/ml, 1000 to 9999
copies/ml, and > or = 10,000 copies/ml categories were 5% (95% CI, 2%-11%), 15%
(95% CI, 11%-20%) and 37% (95% CI, 29%-46% by random effects), respectively. The
area under the receiver operating characteristic (ROC) curve in individual
studies ranged from 0.67 to 1.00. The predictive performance of RNA differed
between cohorts in which different percentages of transmitters had RNA values
>10,000 copies/ml. When 95% of transmitters have RNA values >1000 copies/ml, 77%
of nontransmitters would also have values above this cutoff. Transmission rates
for treated women in the 1000 to 9999 copies/ml category (7%; 95% CI, 4%-11%,)
and > or = 10,000 copies/ml category (18%; 95% CI, 12%-27%) were probably lower
than those for untreated women, whereas the transmission rate for treated women
with <1000 copies/ml was 5% (95% CI, 2%-11 %). Thus, the risk gradient between
RNA categories seems attenuated in treated women. Several aspects of the design,
analysis, and reporting of research in this area may be improved in the future
with attention to selection and observer biases, multivariate adjustment, and
technical consistency. Maternal HIV-1 RNA is a modest predictor of transmission
for individual mothers, but a strong predictor of the average risk in groups of
untreated mothers. Its discriminatory power is better in untreated than in
treated populations and is better in cohorts with a high prevalence of elevated
viral load values than in cohorts with generally low levels of viremia.
PMID- 9637578
TI - Pilot randomized trial of education to improve self-management skills of men with
symptomatic HIV/AIDS.
AB - OBJECTIVE: To evaluate the acceptability, practicality, and short-term efficacy
of a health education program to improve disease self-management in patients with
symptomatic HIV/AIDS. DESIGN: Randomized controlled trial, baseline and 3-month
follow-up questionnaire assessments. SETTING: San Francisco Bay communities.
PARTICIPANTS: Seventy-one men with symptomatic HIV or AIDS were randomly assigned
to a seven-session group educational intervention (N=34) or a usual-care control
group (N=37). INTERVENTION: Interactive health education groups were used to
teach wide-ranging disease self-management skills and information: symptom
assessment and management, medication use, physical exercise, relaxation, doctor
patient communication, and nutrition. Each group was led by two trained peer
leaders (one of whom was HIV-positive) recruited from the community. MAIN OUTCOME
MEASURES: The primary outcome of interest was symptom status. Secondary outcomes
were self-efficacy and health behaviors. Analysis of covariance was used to
compare experimental and control group mean outcomes, adjusting for baseline
value differences. RESULTS: The symptom severity index (number of symptoms
moderate or greater severity) decreased in the experimental, and increased in the
control group (-0.9 versus +0.5; p < .03). Pain, fatigue, and psychological
symptoms were not significantly different between groups. Self-efficacy for
controlling symptoms improved in the experimental, and decreased in the control
group (+4 versus -7; p < .02). Changes in stress/relaxation exercises and
HIV/AIDS knowledge were not different between groups. A trend was shown toward
more frequent physical exercise in the experimental group compared with less in
the control group (+1.3 versus -0.5 times/week; p=.06). CONCLUSIONS: Health
education emphasizing self-management skills for HIV/AIDS patients can be
implemented and evaluated and was accepted by patients, peer-leaders, and health
care providers. Whether this educational program can lead to prolonged
improvement in HIV symptoms and behaviors can be adequately addressed only by a
larger trial of longer duration.
PMID- 9637579
TI - Cardiac manifestations of HIV/AIDS: a review of disease spectrum and clinical
management.
AB - HIV and AIDS involve multiple organ systems. Lungs, brain, skin, gastrointestinal
tract, kidneys, and heart are the major organs targeted by the direct effects of
HIV infection and the secondary opportunistic complications of AIDS. Although
most other organ system involvement has been extensively described in numerous
studies and reviews, cardiac abnormalities related to HIV infection have remained
less well characterized, partially because their pathogenesis was less clear and
their clinical significance was uncertain. Most studies that have described
cardiac complications in AIDS patients were postmortem, although some clinical
series have been reported. It is now clear that cardiac involvement in AIDS
patients is relatively common. Although most such conditions are clinically
quiescent, some may have devastating and fatal outcomes. Pericardial effusion and
myocarditis are among the most commonly reported abnormalities. Cardiomyopathy,
endocarditis, and coronary vasculopathy have also been reported. In this review,
we discuss the most common cardiac abnormalities in HIV-infected patients, as
well as their clinical significance, clinical presentation, and management.
PMID- 9637580
TI - Longitudinal HIV-1 RNA levels in a cohort of homosexual men.
AB - HIV-1 RNA levels measured during early chronic infection strongly predict
subsequent clinical events. In the short term, HIV-1 is in a steady state, but
the stability of viral levels over time is incompletely understood. We used
reverse transcriptase polymerase chain reaction (RT-PCR) to examine changes in
serum HIV-1 RNA levels in 111 HIV-1-infected homosexual men during the period
from 1982 to 1992 and their relation to clinical outcomes. HIV-1 RNA levels
increased by a median of 0.08 log10 copies/ml/year (p=.0001). HIV-1 RNA levels
rose either gradually or abruptly for the majority of subjects; 41% had no
increase. Among subjects surviving at least 8 years, HIV-1 RNA was stable during
the first 4 years after seroconversion (median. 0.00 log10 copies/ml/year), but
rose in years five through eight (median, 0.06 log10 copies/ml/year; p=.04). The
annual HIV-I RNA level was more predictive of AIDS (relative hazard [RH], 1.75
per 0.5 log difference; 95% confidence interval [CI], 1.38-2.21; likelihood ratio
[LR], 26.2) than the initial level alone (RH, 1.39; 95% CI. 1.10-1.76; LR, 8.5).
We conclude that most HIV-1-infected persons lack a long-term viral setpoint and
that failure to account for evolution of the viral level can lead to
underestimation of the risk of progression.
PMID- 9637581
TI - Accelerated changes (inflection points) in levels of serum immune activation
markers and CD4+ and CD8+ T cells prior to AIDS onset.
AB - The trajectories of change in CD4+ and CD8+ lymphocytes and serum neopterin and
beta2-microglobulin (beta2M) levels were determined in 158 HIV-seropositive
individuals during 5.5 years before a clinical AIDS diagnosis. Each patient was
evaluated separately using a two-piece regression model with seven possible
change points to identify any adverse change (inflection point) in the slopes of
each immunologic marker of HIV infection. Two categories of subjects were
distinguished for each marker--those with statistically significant inflection
points and those who demonstrated a steady progression of changes to AIDS. Fifty
nine percent had an inflection point for CD4+ T cells. The frequency of
inflection points for CD8+ was 49%, for serum neopterin -48% and for beta2M -38%.
Inflection points were found over a 4-year span. Three distinctive categories of
inflection points were observed on the basis of their independent occurrence: one
was in CD4+ T cells, another in CD8+ T cells, and a third in the serum markers of
immune activation. The inflection point for CD4+ usually occurred prior to those
for CD8+ T cells (p=.0002). The HIV-positive persons with inflection points were
diagnosed with AIDS when immunologic parameters were significantly more abnormal
than in those with steady progression (p < .0003). Thus, these two groups
differed in the course of immune changes and in the levels of immune
abnormalities associated with the occurrence of clinical AIDS.
PMID- 9637582
TI - Motivation, recruitment, and screening of volunteers for a phase I/II HIV
preventive vaccine trial in Thailand.
AB - Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine
trial in Thailand were evaluated with respect to correlates of participation at
each phase. Correlates included demographic variables, motivation for interest in
the trial, and factors related to communication and contact. Participants were
recruited at two sites through varied methods. The majority of prescreenees
reported altruistic motives for interest in the trial and blood donors emerged as
a group that may have been particularly altruistic. Findings indicated site
differences in attrition during recruitment and screening, but not in enrollment
into the vaccine trial. Blood donation and willingness to be contacted by phone
at home were significantly related to making and keeping screening appointments.
PMID- 9637583
TI - Expansion of clonotypic T-cell populations in the peripheral blood of
asymptomatic Gran Chaco Amerindians infected with HTLV-IIB.
AB - Peripheral blood mononuclear cells from asymptomatic HTLV-II-infected and
uninfected Gran Chaco Amerindians were analyzed using polymerase chain reaction
(PCR) for expansions of T-cell receptor (TCR) V-beta gene clonotypes. Analyses
were performed using primer pairs designed to identify expanded T-cell familial
clonotypes based on their unique TCR beta gene rearrangements. Of the 30 HTLV-IIB
positive samples tested, five showed evidence of V-beta clonotypic T-cell
expansion. Of the five expansions, two were monoclonotypic and the remaining
three were oligoclonotypic. In comparison, 30 HTLV-II-negative Amerindians showed
no evidence of clonotypic T-cell expansion. Amplified DNA from one of the
monoclonotypic samples was subsequently cloned and sequenced and was found to
have uniform variable/ diversity/joining sequences confirming its unique
monoclonal T-cell expansion. This method of detecting clonal TCR beta gene
rearrangements has the advantage over traditional Southern blot techniques of
being more sensitive and specific even with suboptimal specimens. The prognostic
significance of clonotypic T-cell expansion in a group such as the HTLV-II
infected Gran Chaco Amerindians remains to be determined.
PMID- 9637584
TI - Associations among HTLV-I, HTLV-II, and HIV in injecting drug users in Salvador,
Brazil.
PMID- 9637585
TI - HTLV-I/II seropositivity in populations at high risk for HIV-1 infection in
Cordoba City, Argentina.
PMID- 9637586
TI - Immunomodulatory effects of concurrent HTLV-I infection in strongyloidiasis.
PMID- 9637587
TI - First report of HIV-2 infection in Argentina.
PMID- 9637588
TI - The EEG findings in extratemporal seizures.
AB - Extratemporal seizures originate from the frontal, central, parietal, occipital,
and midline regions of the brain. The scalp EEG can show various types of
interictal and ictal discharges consisting of spikes, spike and wave sharp waves,
paroxysmal fast activity, or rhythmic activity in the beta, alpha, theta, or
delta frequency ranges. The discharges can occur as focal, regional, lateralized,
or secondarily generalized discharges. Discharges arising from the frontal region
are varied and at times complex. Centro-temporal spikes associated with benign
epilepsy of childhood have a characteristic blunt spike and wave appearance.
Centro-parietal spikes can occur in children with benign childhood epilepsy or in
association with symptomatic epilepsies at any age. Occipital spike discharges
have been seen in young children with visual problems, benign occipital epilepsy
of childhood, the Sturge-Weber syndrome, and other symptomatic or structural
lesions involving the occipital lobe. There may be problems with detection of the
source of origin of seizures secondary to the anatomy of the various regions,
deep foci, small restricted foci, rapid spread of epileptiform discharges, and
contaminating effects of muscle and movement artifact. Depth or intracranial
recordings may help in further localization of foci.
PMID- 9637589
TI - The benign occipital epilepsies of childhood: an overview of the idiopathic
syndromes and of the relationship to migraine.
AB - Benign occipital epilepsy of childhood is an idiopathic partial epilepsy syndrome
with elementary visual symptomatology, frequently associated with other ictal
phenomena. Seizures are usually followed by postictal headache and are often
associated with interictal occipital rhythmic paroxysmal EEG activity that
appears only after eye closure. In some children the ictal visual symptoms or the
interictal EEG abnormalities may not be demonstrated. The clinical and/or EEG
manifestations of other forms of idiopathic partial or generalized epilepsy may
be found in association. Occipital spikes in non-epileptic children with
defective vision, occipital slow spike-and-wave found in some patients with the
Lennox-Gastaut syndrome, focal epilepsy due to occipital lesions, seizures
originating in the temporal lobe secondary to an occipital abnormality, and
complicated or basilar migraine must be considered in the differential diagnosis.
Early-onset benign occipital epilepsy or seizure susceptibility syndrome deserves
to be considered separately. It has been defined by Panayiotopoulos as consisting
of brief, infrequent attacks or prolonged status epilepticus and characterized by
ictal deviation of the eyes and/or head and vomiting, occurring in children
usually between the ages of 3 and 7 years. Advances in molecular genetics will
help decide whether these two disorders are indeed distinct. Benign occipital and
benign rolandic epilepsy are commonly associated with migraine. The selective
involvement of the occipital lobe in migraine has not been fully explained. The
association between benign occipital epilepsy and migraine is likely related to
this underlying mechanism as well. The "fixation off" phenomenon or blocking of
occipital epileptic discharges by eye opening is not specific to benign occipital
epilepsy of childhood and may be found in symptomatic epilepsies as well.
Migraine and epilepsy are distinct disorders, both as far as their
pathophysiologic mechanisms and clinical symptomatology are concerned. There is
however an overlap in some patients and a causal relationship may exist in some,
leading to clinically distinct migraine epilepsy syndromes. Here too,
clarification of the molecular basis of migraine and of epilepsy will throw light
on the nature of the relationship between the two conditions.
PMID- 9637590
TI - Symptomatic occipital lobe epilepsy.
AB - Symptomatic occipital lobe epilepsy is increasingly recognized among patients
with partial-onset seizures. Although traditional clinical and
electroencephalographic criteria had defined occipital lobe epilepsy in the past,
new neuroimaging techniques and the recognition of specific syndromes associated
with occipital lobe epilepsy have improved the diagnosis and management of these
patients. These syndromes include, among others, lesional occipital lobe epilepsy
(congenital vs. acquired), MELAS, and epilepsy with bilateral occipital
calcifications. The diagnosis of symptomatic occipital lobe epilepsy is improving
as functional and structural neuroimaging techniques enable the detection of
subtle abnormalities in such patients. This has had a direct impact on the
correct classification of patients with benign occipital lobe epilepsy, basilar
migraine, and symptomatic occipital lobe epilepsy. The common clinical symptoms,
EEG patterns, and neuroimaging findings of these patients are discussed.
PMID- 9637591
TI - Benign epilepsy of childhood with centrotemporal spikes.
AB - Benign epilepsy of childhood with centrotemporal spikes (BECT) is the most common
partial epilepsy syndrome in the pediatric age group, with an onset between age 3
and 13 years. The typical presentation is a partial seizure with parasthesias and
tonic or clonic activity of the lower face associated with drooling and
dysarthria. Seizures commonly occur at night and may become secondarily
generalized. They are usually infrequent and may not require antiepileptic drugs
but, if treated, they tend to be easily controlled. Children with BECT are
neurologically and cognitively normal. The EEG shows characteristic high-voltage
sharp waves in the centrotemporal regions, which are activated with drowsiness
and sleep. In this typical form, BECT is easily recognized. However, atypical
cases are common and the definition of BECT can become blurred. Although further
investigations are not required in cases with typical clinical and EEG findings
and normal neurologic examinations, neuroimaging studies may be required in
atypical cases to rule out other pathology. The long-term medical and
psychosocial prognosis of BECT is excellent, with essentially all children
entering long-term remission by mid-adolescence.
PMID- 9637592
TI - Surgical treatment for perirolandic lesional epilepsy.
AB - Our purpose was to evaluate the safety and efficacy of surgical treatment for
perirolandic lesional epilepsy. We analyzed the records of 14 consecutive
patients who underwent a stereotactic lesionectomy for intractable partial
epilepsy between 1985 and 1994. All patients had a neuroimaging-identified lesion
in the perirolandic cortex. The mean duration of follow-up was 6 years (range 1
11 years). Thirteen patients (93%) had a significant improvement in seizure
tendency. Eleven patients (78%) were rendered seizure-free. Morbidity occurred in
only one patient, who experienced an increased monoparesis after surgery.
Stereotactic lesionectomy is an effective surgical strategy in patients with
perirolandic lesional epilepsy. The recent development of functional brain
imaging using subtraction ictal single-photon emission computed tomography co
registered with volumetric magnetic resonance imaging has been shown to be a
reliable indicator of epileptic brain tissue that may significantly alter the
preoperative evaluation in patients with extratemporal seizures.
PMID- 9637593
TI - Mesial frontal epilepsy.
AB - The mesiofrontal cortex comprises a number of distinct anatomic and functional
areas. Structural lesions and cortical dysgenesis are recognized causes of mesial
frontal epilepsy, but a specific gene defect may also be important, as seen in
some forms of familial frontal lobe epilepsy. The predominant seizure
manifestations, which are not necessarily strictly correlated with a specific
ictal onset zone, are absence, hypermotor, and postural tonic seizures. Other
seizure types also occur. The task of localization of the epileptogenic zone can
be challenging, whether EEG or imaging methods are used. Successful localization
can lead to a rewarding outcome after epilepsy surgery, particularly in those
with an imaged lesion.
PMID- 9637594
TI - Lateral frontal lobe seizures.
AB - On the basis of cytoarchitectural and functional studies, the frontal lobe can be
subdivided into the primary motor cortex, premotor cortex, prefrontal cortex, and
the limbic and paralimbic cortices. However, we are still a long way from clearly
identifying individual frontal lobe epilepsies. Instead, we are limited to a
discussion of frontal lobe seizures arising from various regions of the frontal
lobe. Supplementary motor area epilepsy and perirolandic epilepsy have been quite
well defined, in contrast to syndromes involving other regions of the frontal
lobe. Recent technological advances in neuroimaging, electroencephalography,
magnetoencephalography and detailed videotape analysis of seizure semiology may
enable us to delineate these frontal lobe syndromes with better accuracy, thereby
improving outcome after epilepsy surgery.
PMID- 9637595
TI - Motor and sensory mapping of the frontal and occipital lobes.
AB - In patients with intractable epilepsy, surgical resections are performed with the
primary goal of improving seizure control. The risk is that the resections may
also remove tissues crucial for normal activities. The goal of surgical planning
is therefore to determine as accurately as possible the regions of seizure onset
and the regions controlling important functions, so that one can determine what
to remove and what to leave in place. Clinical functional localization has been
performed using cortical stimulation for over half a century, using both
intraoperative and extraoperative methods. Signal averaging also has been widely
used. More recently, techniques based on analysis of EEG in the frequency domain
have shown promise. The methods appear to accurately indicate the function of the
region assessed but do not necessarily predict functional consequences of
resection. We review these methods, their indications, and the results obtained
by their use.
PMID- 9637596
TI - Multiple subpial transection in patients with extratemporal epilepsy.
AB - Multiple subpial transection (MST) was developed to permit the treatment of
partial epilepsies that reside in or encroach on eloquent cortex (language and
sensorimotor cortex). It was conceived after the discoveries of the columnar
organization of neocortex and that expression and spread of seizures utilize the
transverse fiber network. Although the technique is simple in principle, it takes
a skilled and practiced hand to avoid damage to the neocortical columns and
vascular supply. The efficacy in controlling seizures with MST in extratemporal
epilepsy is similar to that of resective surgery. Activities of daily living are
not adversely impacted by MST. MST is a viable alternative to resection in
extratemporal epilepsy.
PMID- 9637597
TI - Seizure patterns of Mongolian gerbils subjected to a prolonged weekly test
schedule: evidence for a kindling-like phenomenon in the adult population.
AB - PURPOSE: Mongolian gerbils (Meriones unguiculatus) seize in response to sensory
stimulation and forced exploratory behavior, but the incidence and severity of
their seizures are variable. We wished to characterize the seizure pattern of
gerbils from our breeding colony. METHODS: Ninety-three gerbils aged 1-16 months
were tested for a mean of 24 consecutive weeks and assigned to a category
according to their seizure pattern. Frequency distribution histograms of the mean
scores assigned every 5 weeks were plotted for each category. Mean age, number of
seizures, onset of the first facial and forelimb myoclonus, and of the first
generalized tonic-clonic seizure (GTCS) were compared among categories. We
performed correlation analysis between onset of seizures and animal age. RESULTS:
From the 93 tested, no seizure-resistant gerbils could be isolated. Four major
categories were distinguished. Category 1, highly seizure-sensitive gerbils
(39%), exhibited seizures from the first few weeks of test on. Category 2,
consisting of approximately 37%, were seizure-free for the first three to six
consecutive tests, later developing facial and forelimb myoclonus and eventually
GTCS. Because such progressive development of seizures was similar to that
occurring upon electrical kindling, the gerbils were classified as kindled-like
(KL). Among KL gerbils, older individuals were significantly more refractory to
seizures. In category 3, gerbils (10%) exhibited inconsistent seizure behavior.
Category 4 consisted of significantly younger animals (11%) with rapid progress
to generalized seizures. CONCLUSIONS: Seizures of progressive severity can be
induced in adult gerbils with a prolonged test regimen. As a consequence, the
number of regularly seizing gerbils in a colony can be increased. Prolonged tests
starting at a defined age may help characterize seizure development better in
this genetic model of limbic epilepsy.
PMID- 9637598
TI - [31P]/[1H] nuclear magnetic resonance study of mitigating effects of GYKI 52466
on kainate-induced metabolic impairment in perfused rat cerebrocortical slices.
AB - PURPOSE: Kainic acid (KA) has long been used in experimental animals to induce
status epilepticus (SE). A mechanistic implication of this is the association
between excitotoxicity and brain damage during or after SE. We evaluated KA
induced metabolic impairment and the potential mitigating effects of GYKI 52466
[1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] in
superfused rat cerebral cortical slices. METHODS: Interleaved [31P]/[1H] magnetic
resonance spectroscopy (MRS) was used to assess energy metabolism, intracellular
pH (pHi), N-acetyl-L-aspartate (NAA) level, and lactate (Lac) formation before,
during, and after a 56-min exposure to 4 mM KA in freshly oxygenated artificial
cerebrospinal fluid (oxy-ACSF). RESULTS: In the absence of GYKI 52466 and during
the KA exposure, NAA, PCr, and ATP levels were decreased to 91.1 +/- 0.8, 62.4 +/
3.9, and 59.1 +/- 4.3% of the control, respectively; Lac was increased to 118.2
+/- 2.1 %, and pH, was reduced from 7.27 +/- 0.02 to 7.13 +/- 0.02. During 4-h
recovery with KA-free ACSF, pHi rapidly and Lac gradually recovered, NAA
decreased further to 85.5 +/- 0.3%, and PCr and ATP showed little recovery.
Removal of Mg2+ from ACSF during KA exposure caused a more profound Lac increase
(to 147.1 +/- 4.0%) during KA exposure and a further NAA decrease (to 80.4 +/-
0.5%) during reperfusion, but did not exacerbate PCr, ATP, and pHi changes.
Inclusion of 100 microM GYKI 52466 during KA exposure significantly improved
energy metabolism: the PCr and ATP levels were above 76.6 +/- 2.1 and 82.0 +/-
2.9% of the control, respectively, during KA exposure and recovered to 101.4 +/-
2.4 and 95.0 +/- 2.4%, respectively, during reperfusion. NAA level remained at
99.8 +/- 0.6% during exposure and decreased only slightly at a later stage of
reperfusion. CONCLUSIONS: Our finding supports the notion that KA-induced SE
causes metabolic disturbance and neuronal injury mainly by overexcitation through
non-N-methyl-D-aspartate (NMDA) receptor functions.
PMID- 9637599
TI - Phenytoin blocks the reversal of a classically conditioned discriminative
eyeblink response in rabbits.
AB - PURPOSE: Cognitive deficits associated with chronic treatment with phenytoin
(PHT) have been reported. PHT blocks transfer from a signaled appetitive bar
press to an active avoidance response in rats. We investigated the effects of PHT
and the prodrug fosphenytoin in rabbits required to learn a discrimination and
reversal of a classical eyeblink conditioning paradigm. METHODS: Before drug
treatment was started, rabbits were trained to produce a discriminated eyeblink
response. PHT (n = 7) was administered centrally or the prodrug fosphenytoin (n =
2) was given systemically. Control animals were similarly treated centrally with
either saline (n = 3) or no drug treatment (n = 13). Rabbits were then challenged
with a stimulus reversal while being maintained on the respective drug. RESULTS:
On the first day of reversal training, control animals typically displayed high
response rates to both tones, followed by a reduction in responsiveness to the
new conditioned stimulus (CS-) in the ensuing days. In contrast, PHT-treated
animals failed to suppress responsiveness to the new CS-. CONCLUSIONS: The
response patterns observed are similar to those observed in rabbits with
hippocampal ablations, leading us to suggest that the adverse effects of
phenytoin may be due to actions in the hippocampus.
PMID- 9637600
TI - Oral health and dental treatment needs in Nigerian patients with epilepsy.
AB - PURPOSE: We determined the prevalence of oral disorders and the dental treatment
needs of outpatients with epilepsy. METHODS: A questionnaire was administered to
56 consecutive patients (35 males, 21 females) presenting to an outpatient
clinic. All patients underwent dental examinations. The clinical and diagnostic
features of each patient's epilepsy were also obtained. RESULTS: The mean age (+/
SD) of the patients was 25.1 +/- 12.1 years (range, 12-56 years). Of 9 patients
receiving phenytoin (PHT) monotherapy, 3 (33.3%) had gingival hypertrophy; 15 of
18 (83.3%) patients receiving PHT in combination with phenobarbital (PB)
manifested the disorder. Traumatized anterior teeth were found in 26 (46.4%)
patients with the males significantly more affected than females (p = 0.02). When
the dental treatment needs were considered, 24 (42.9%) patients required dental
prophylaxis with oral hygiene instruction, and an equal number required various
types of restorative treatments. Only 13 patients (23.2%) had previously visited
a dental clinic; the 43 (76.8%) who had never sought dental treatment claimed
they did not see any need for it. CONCLUSIONS: Our study showed an increased
predilection to anterior dental injuries in patients with epilepsy as compared
with the prevalence earlier reported for those without epilepsy in Nigeria (p =
0.00). There is a clear need for effective interaction between medical and dental
practitioners in the management of epilepsy.
PMID- 9637601
TI - Symptoms of depression and anxiety in pediatric epilepsy patients.
AB - PURPOSE: We assessed rates of symptoms of anxiety and depression among pediatric
patients with epilepsy. METHODS: We administered the Revised Child Manifest
Anxiety Scale (RCMAS), and Child Depression Inventory (CDI) to 44 epilepsy
patients aged 7-18 years (mean age 12.4 years). Demographic, socioeconomic, and
epilepsy-related information was examined in relation to depression and anxiety
scores. RESULTS: No patients had been previously identified to have depression or
anxiety. However, 26% had significantly increased depression scores and 16% met
criteria for significant anxiety symptomatology. CONCLUSIONS: Symptoms of
depression and anxiety are common among pediatric patients with epilepsy and
appear to be overlooked by care providers.
PMID- 9637602
TI - Surgical outcome in patients with epilepsy with occult vascular malformations
treated with lesionectomy.
AB - PURPOSE: This retrospective study reports the long-term surgical outcome of
patients with medically refractory epilepsy and vascular malformations who were
treated with lesionectomy. A detailed analysis of surgical failures had been
performed in an attempt to define predictors of surgical success and failure.
METHODS: Fifteen patients with medically intractable epilepsy and
angiographically occult vascular malformations (AOVMs) were treated surgically
with lesionectomy at Duke University Medical Center. Lesionectomy consisted of
removal of the AOVM and surrounding hemosiderin-stained brain only, without the
use of electrocorticography (ECoG) to guide resection. RESULTS: Eleven (73%)
patients are seizure free after lesionectomy. Three showed no significant
improvement, and one patient died, presumably after a seizure. Age of onset,
duration of seizures, age at resection, and gender did not affect outcome. All
patients with neocortical AOVMs in whom EEG findings correlated with the site of
the lesion were seizure free after lesional resection. Treatment failures were
associated with the presence of multiple intracranial lesions, poorly localized
or diffuse EEG findings, discordant positron emission tomography (PET) imaging,
or with a lesion in close proximity to the limbic system. CONCLUSIONS:
Lesionectomy, with removal of surrounding hemosiderin-stained brain, can be
considered the procedure of choice in carefully selected patients with epilepsy
with occult vascular malformations.
PMID- 9637603
TI - Ictal scalp EEG in unilateral mesial temporal lobe epilepsy.
AB - PURPOSE: We wished to determine the predictive significance of unilateral
hippocampal atrophy and interictal spikes on localization of ictal scalp EEG
changes and assess whether ictal EEG provides information that might change
treatment or influence prognosis in patients with such characteristics of
epilepsy. METHODS: We analyzed EEG seizure patterns in 118 seizures in 24
patients with unilateral mesial temporal lobe epilepsy (MTLE) defined by typical
clinical seizure semiology, unilateral hippocampal atrophy on magnetic resonance
imaging (MRI) and unitemporal spikes on interictal EEG. Two blinded
electroencephalographers independently determined morphology, location, and time
course of ictal EEG changes. RESULTS: Lateralization was possible in 88.4-92.0%
of seizures and always corresponded to the side of the interictal spike focus and
of hippocampal atrophy on MRI. Although only 30.4-33.9% of seizures were
lateralized at onset, a later significant pattern emerged (12.6-13.3 s after EEG
seizure onset) that allowed lateralization in 82.4-91.0% of seizures with
nonlateralized onset. Interobserver reliability for lateralization was excellent,
with a K-value of 0.85. In most patients, either all (79.2-83.3%) or >50% (8.3
16.7%) of seizures were lateralized. In only a small proportion of patients (4.2
8.3%) were <50% of seizures lateralized. In 1 patient, no seizure could be
lateralized by 1 electroencephalographer. The results of ictal EEG recordings did
not alter the surgical approach and did not correlate with surgical outcome.
CONCLUSIONS: We conclude that unilateral hippocampal atrophy on MRI and
unitemporal interictal spikes can predict localization of ictal scalp EEG changes
with a high degree of reliability and that ictal EEG provides no additional
localizing information in this particular patient group.
PMID- 9637604
TI - Real-time automated detection and quantitative analysis of seizures and short
term prediction of clinical onset.
AB - PURPOSE: We describe an algorithm for rapid real-time detection, quantitation,
localization of seizures, and prediction of their clinical onset. METHODS:
Advanced digital signal processing techniques used in time-frequency
localization, image processing, and identification of time-varying stochastic
systems were used to develop the algorithm, which operates in generic or
adaptable "modes." The "generic mode" was tested on (a) 125 partial seizures
(each contained in a 10-min segment) involving the mesial temporal regions and
recorded using depth electrodes from 16 subjects, and (b) 205 ten-minute segments
of randomly selected interictal (nonseizure) data. The performance of the
algorithm was compared with expert visual analysis, the current "gold standard."
RESULTS: The generic algorithm achieved perfect sensitivity and specificity (no
false-positive and no false-negative detections) over the entire data set.
Seizure intensity, a novel measure that seems clinically relevant, ranged between
35.7 and 6129. Detection was sufficiently rapid to allow prediction of clinical
onset in 92% of seizures by a mean of 15.5 s. CONCLUSIONS: This algorithm, which
was implemented with a personal computer, represents a definitive step toward
rapid and accurate detection and prediction of seizures. It may also enable
development of intelligent devices for automated seizure warning and treatment
and stimulate new study of the dynamics of seizures and of the epileptic brain.
PMID- 9637605
TI - Predictive value of interictal epileptiform discharges during non-REM sleep on
scalp EEG recordings for the lateralization of epileptogenesis.
AB - PURPOSE: EEG recording during sleep is widely used in the assessment of epilepsy,
particularly in candidates for surgery, yet the diagnostic value of this
procedure is not well established. We evaluated the predictive reliability of
interictal epileptiform discharges (IEDs) for localization in presurgical
patients with temporal lobe epilepsy (TLE) during non-REM sleep. METHODS:
Preoperative scalp EEG recordings with waking and sleep states were assessed in
83 patients with TLE in whom localization of the epileptogenic zone was
subsequently confirmed by successful surgical treatment (patient seizure-free >1
year). RESULTS: The accuracy of EEG recordings for prediction of lateralization
significantly changed from 51.8% during waking to 78.3% during sleep. After
exclusion of patients who showed no discharges, the predictive value changed from
74.1 to 86.7%. However, in patients in whom the waking scalp EEG lateralized
incorrectly, no improvement in reliability was achieved by sleep recording.
CONCLUSIONS: Our results suggest that IEDs occurring in non-REM sleep provide
more accurate information for lateralization of epileptogenesis than do those
occurring during waking. This gain of diagnostic information was obtained in
patients who showed either bilateral or no discharges in waking records, because
unilateral discharges arising de novo in sleep were always correctly
lateralizing. On the other hand, in patients who showed unilateral discharges in
the awake state, whether ipsilateral or contralateral to the epileptogenic zone,
the findings were generally unchanged during sleep.
PMID- 9637606
TI - Longitudinal quantitative hippocampal magnetic resonance imaging study of adults
with newly diagnosed partial seizures: one-year follow-up results.
AB - PURPOSE: We wished to establish whether hippocampal changes occur in 1 year in
adults with newly diagnosed partial seizures and, if so, to identify possible
causes and mechanisms. METHODS: Thirty-six adult patients with newly diagnosed
partial seizures underwent a magnetic resonance imaging (MRI) scan of the brain
including hippocampal volume and T2 relaxation time (HCT2) measurement and had a
follow-up quantitative MRI scan approximately 1 year after the baseline MRI scan.
RESULTS: At baseline, 4 patients (11%) had hippocampal sclerosis (HS), 4 (11%)
had abnormalities other than HS, and 28 had a normal MRI scan (78%). Twenty-three
patients (64%) had recurrent seizures in the period between the two MRI scans.
One of the 4 patients with HS, who had daily seizures, had significantly
increased HCT2 values on follow-up, possibly reflecting progressive hippocampal
damage. None of the 32 patients with MRI findings other than HS at baseline
progressed to HS on follow-up. However, 2 of the 32 patients had significant
hippocampal changes, probably related to resolution of inflammatory swelling or
edema after seizures were controlled. CONCLUSIONS: Subtle changes in hippocampi
can occur in 1 year in adults with newly diagnosed partial seizures, which could
be due to resolution of edema after seizure control or to hippocampal changes
associated with frequent and daily seizures. Follow-up of the studied cohort for
several years will be required to settle the question of whether progressive
hippocampal damage occurs in temporal lobe epilepsy (TLE).
PMID- 9637607
TI - Cerebellar changes in partial seizures: clinical correlations of quantitative
SPECT and MRI analysis.
AB - PURPOSE: To determine the frequency and patterns of periictal cerebellar
hyperperfusion, whether it is associated with increased cerebellar atrophy, and
whether cerebellar hyperperfusion and cerebellar atrophy are associated with
predisposing clinical factors or with the outcome of epilepsy surgery. METHODS:
Periictal and interictal SPECT scans and volumetric brain magnetic resonance
imaging (MRI) were quantitatively analyzed in 54 consecutive patients with
medically refractory partial epilepsy. Their histories were reviewed and their
postsurgical outcomes assessed. RESULTS: Significant periictal cerebellar
hyperperfusion was found in 26 (48.1%) patients, of whom 18 had CCH, two had
homolateral cerebellar hyperperfusion (HCH), and six had symmetrical bilateral
hyperperfusion (BCH). No relation found between the site of the SPECT seizure
localization and the presence or type of cerebellar hyperperfusion. CCH was more
common when the injected seizure involved unilateral clonic motor activity (p <
0.05). A smaller MRI relative cerebellar volume (cerebellar volume/cerebral
volume) was correlated with a greater seizure frequency (Rs = -0.30; p < 0.05)
but not with the duration of epilepsy. There was no difference in the cerebellar
volumes between the different patterns of cerebellar perfusion (p > 0.05).
However, patients without a focal structural MRI lesion had significantly smaller
cerebellar volumes (p < 0.05). In patients who underwent epilepsy surgery (n =
31), there was a trend for those without excellent outcomes to have smaller
relative cerebellar volumes than did those with excellent outcome (10.6 vs.
11.8%; p = 0.08). CONCLUSIONS: Periictal changes in cerebellar perfusion,
particularly CCH, are common in patients with intractable partial epilepsy.
However, periictal hyperperfusion does not appear to be a major contributor to
the development of cerebellar atrophy.
PMID- 9637608
TI - Bilateral temporal hypometabolism in epilepsy.
AB - PURPOSE: Positron emission tomography (PET) has proven useful in epilepsy surgery
for its ability to identify unilateral temporal hypometabolism (UTH), which is
predictive of good surgical outcome. The significance of bilateral temporal
hypometabolism (BTH) is not known. METHODS: We identified all patients who had
marked bilateral reduction in temporal lobe metabolism relative to the cerebellar
hemispheres and compared their clinical features and treatment outcomes with
those of control patients with UTH. RESULTS: BTH was evident in 10% of PET scans
for epilepsy at our institution. We compared these patients with age-matched
controls with UTH. The BTH patients had a higher percentage of generalized
seizures; were more likely to have bilateral, diffuse or extratemporal seizure
onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings.
UTH patients were more likely to have unilateral mesial temporal atrophy on MRI.
Even when electrical seizure onsets were well localized, surgical outcomes were
markedly worse in these patients than in controls. Medical treatment was also
less successful. Social and cognitive functioning was worse in the BTH group. The
only death occurred in the group with BTH. CONCLUSIONS: Patients with BTH have
features distinct from those with UTH and have a worse prognosis for seizure
remission after surgery.
PMID- 9637609
TI - Myoclonic absence-like seizures and chromosome abnormality syndromes.
AB - PURPOSE: We explored the relationship between myoclonic absence seizures (MAS)
and underlying chromosome disorders. METHODS: Among 14 patients with MAS observed
in three centers, 5 had typical cryptogenic myoclonic absence epilepsy (MAE), 2
had MAS associated with other seizure types (1 with signs of a neuronal migration
abnormality and 1 with signs of a metabolic disorder), and 7 had MAS, with or
without other seizure types, complicating a chromosome abnormality syndrome-2
with trisomy 12p, 4 with Angelman syndrome, and 1 with inv dup (15). RESULTS: In
the 7 patients with chromosomopathy, MAS appeared at a mean age of 2.9 years
(range 4 months to 6 years 6 months), had a duration of 4-20 s, and were
accompanied by reduced awareness and rhythmic myoclonic jerks involving proximal
limb muscles. Ictal EEG showed 2- to 3-Hz generalized spike-and-wave discharges.
CONCLUSIONS: In these patients, MAS differed slightly from those of typical MAE:
age of onset was earlier, absences were of shorter duration, and no clear
increase in muscular tone was noted. Abnormal expression of genes codifying for
the subfamily of K+ channels and for gamma-aminobutyric acid-3 subunit receptors
(GABRB3), both located in the chromosome segments involved in the
chromosomopathies presented by our patients, could be responsible for the same
generalized seizure type. Chromosome analysis should be performed in patients
with mental retardation and MAS, especially when the ictal pattern does not
completely overlap that observed in MAE.
PMID- 9637610
TI - Fixation-off and eyes closed catamenial generalized nonconvulsive status
epilepticus with eyelid myoclonic jerks.
AB - PURPOSE: Eyelid myoclonic jerks have been described in fixation-off-sensitive
(FOS) epilepsy, but their relationship to nonconvulsive status epilepticus (NCSE)
or to catamenial exacerbations is little reported. METHODS: We describe a woman
of normal intelligence with catamenial periods of prolonged NCSE who exhibited
various intra- and interseizure thresholds of polyspike suppression when her eyes
were open, with particular visual inputs and with antiepileptic drug (AED)
treatment. RESULTS: In one episode, on the first day of the woman's menstrual
period, bursts of bilateral synchronous polyspike activity were briefly
suppressed with visual fixation but were more lastingly suppressed after
administration of lorazepam (LZP). During another period of NCSE, the SE was
completely suppressed by visual fixation on objects and patterned checkerboard
screens and by ocular convergence, was incompletely suppressed when her eyes were
open in a dark room and when her eyes were open without visual fixation, but was
not suppressed by mental activation alone. CONCLUSIONS: FOS polyspike bursts with
eyelid myoclonic jerks may exhibit catamenial exacerbations, varying from
completely suppressible with visual fixation to nonsuppressible during NCSE.
These findings suggest an interplay between humoral factors, AEDs, and seizure
threshold in this condition.
PMID- 9637611
TI - Prolonged coma and severely attenuated EEG after a single seizure.
AB - A 63-year-old woman presented with a comatose state after a fall. Results of
cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans were
normal. An EEG recorded 5 h after admission was very severely attenuated and
slowed. Consciousness and EEG were improved the next day. No cause was detected
initially. After sleep deprivation, the patient had a generalized seizure
followed by a similar coma and EEG. Even a single seizure may cause a prolonged
coma with a very severely attenuated and slowed EEG.
PMID- 9637612
TI - Nonconvulsive status epilepticus in two patients receiving tiagabine treatment.
AB - In the course of an open study on the add-on treatment of tiagabine (TGB) in
patients with localization-related epilepsy syndromes, 2 of 9 patients developed
nonconvulsive status epilepticus (NCSE) with electroclinical features consistent
with those of atypical absence seizures. One patient had never had atypical
absence seizures before. In both cases, immediate discontinuation of TGB was
followed by complete and sustained electroclinical remission; we suggest a
possible causative role of TGB. This observation may be consistent with a
paradoxical effect of TGB in selected cases. Possible risk factors and a
pathophysiological hypothesis are discussed.
PMID- 9637613
TI - The future of aneurysm surgery.
PMID- 9637614
TI - The future of aneurysm surgery.
PMID- 9637615
TI - The future of aneurysm surgery.
PMID- 9637616
TI - The future of aneurysm surgery.
PMID- 9637617
TI - The future of aneurysm surgery.
PMID- 9637618
TI - Endoscopic transforaminal lumbar discectomy and reconfiguration: a postero
lateral approach into the spinal canal.
AB - BACKGROUND: In the past, minimally invasive procedures (chemonucleolysis, laser,
automated percutaneous discectomy, percutaneous manual nucleotomy, arthroscopy)
have been largely confined to intradiscal work. This study represents cases of
working channel, transforaminal spinal endoscopy performed using an endoscope
which, because of its small size and flexibility, can bend up to 90 degrees
(depending on the guiding cannula), and pass completely through the foramen into
the spinal canal (truly transforaminal, as opposed to just going through part of
the foramen and into the disc), to directly remove free fragments and reconfigure
disc, relieving root and dural displacement at all lumbar levels. METHODS: The
records of 533 patients who had outpatient, minimally invasive operations
performed over a 6-year period (ending in 1995) by this author were analyzed. Of
these, 110 had small scope transforaminal procedures, forming the basis of this
study. RESULTS: An independent observer followed the 110 patients who had
endoscopic transforaminal procedures for 2 or more years. Using MacNab's
criteria, the success rate (excellent or good) was 95% in the 75 patients with
disc presenting lateral to the dura-"lateral presenting,"-and 83% in the 35
patients not presenting disc for direct removal-"non-lateral presenting" (i.e.,
dura in the pathway)-making an overall success rate of 91%. One patient who
developed discitis was the only complication. CONCLUSION: Guideable endoscopes
small enough to pass completely through the foramen allow percutaneous surgery to
include non-contained disc herniations and even some migrated free fragments,
depending on the location. The percutaneous transforaminal endoscopic technique
can be an effective, safe approach for disc removal through the foramen,
especially in cases where the disc presents itself for direct removal.
PMID- 9637619
TI - Thoracic disc herniations: transthoracic, lateral, or posterolateral approach? A
review.
AB - BACKGROUND: The choice between transthoracic, lateral, and posterolateral
approaches to excise thoracic disc herniations remains controversial. METHODS:
The outcome of the three approaches was compared in seven of the authors' cases
and in 324 other cases reported in the literature. RESULTS: Partial or total
neurological recovery was found in 93% after a transthoracic procedure versus 87%
after a posterolateral technique and 80% after a lateral approach (P < 0.05). A
trend toward superior results after a transthoracic technique was also noted in
subgroups of patients with radiculopathy, patients with intradural disc
herniations, and patients with multiple lesions, although statistical
significance was not reached. Pulmonary complications occurred in 7% of
transthoracic techniques versus 5% in lateral and 0% in posterolateral techniques
(p < 0.025). CONCLUSIONS: The transthoracic approach is recommended for all
thoracic disc herniations below the T4 level except for patients with serious
pulmonary compromise.
PMID- 9637620
TI - Review: complications of surgery for thoracic disc disease.
AB - BACKGROUND: Thoracic discectomy has evolved over the last 60 years from resection
through standard laminectomy, to posterolateral procedures to open thoracotomy
and finally thoracoscopy. Comparison of relative morbidity and mortality between
these approaches is now possible. METHODS: Peer-reviewed publications reporting
clinical data relating to thoracic discectomy, and which provided sufficient
information to enable adequate assessment of mortality and morbidity were
reviewed. These articles were determined via review of the results of MedLine
searches and articles gathered through compilation of references from those
articles. RESULTS: Articles reviewed spanned a period of over 60 years. Surgical
procedures used for thoracic discectomy included laminectomy, pediculectomy,
costotransversectomy, lateral extracavitary, transverse arthropediculectomy,
anterolateral thoracotomy, and thoracoscopy. Complications included death,
paralysis, paresis, loss of bowel and/or bladder control, pulmonary embolism,
pneumonia, atelectasis, compression fracture, infection, pleural tear, bowel
obstruction, and anesthesia dolorosa. Mortality dropped to nearly zero after
development of anterior and posterolateral approaches. Morbidity seems relatively
similar between most procedures other than laminectomy. Not enough procedures
have been reported using thoracoscopy to adequately assess its morbidity.
CONCLUSION: Comparison of relative rates of morbidity and mortality between
surgical approaches to thoracic discectomy suggest that laminectomy does not
provide adequate access for the safe removal of these lesions. Choice of approach
among the alternatives should be based on the evacuation of the herniated
fragment and experience of the surgeon. Thoracoscopy, although promising, has not
had sufficient time for evaluation of morbidity to make definite statements
regarding its safety.
PMID- 9637621
TI - Management options in thoracolumbar burst fractures.
AB - BACKGROUND: Both surgery and recumbency have been adopted in the treatment of
spinal fractures. Herein we present the indications for each, and our experience
with thoracolumbar junction (T12, L1 and L2) burst fractures. METHODS: Sixty
eight patients with thoracolumbar burst fractures were treated operatively in 36
cases, and nonoperatively in 32 with recumbency for 1-6 weeks. Treatment was
based on clinical and radiological criteria. Eighty-one percent of the recumbency
patients, but only 14% of the surgical patients were intact on admission.
Patients were followed for a mean+/-SD of 9+/-10 months in the recumbency group,
and 21+/-21 months in the surgical group. RESULTS: Neurological improvement and
progressive angular deformity occurred in both groups. The cost of recumbency in
our patients was nearly half that of those who required surgery, though the
length of hospitalization between the two groups was similar at 1 month +/-2
weeks. CONCLUSION: The above study emphasizes that the selection of operative
versus nonoperative treatment in burst fractures should not be random but based
on clinical as well as radiological criteria. Recumbency is favored in patients
who are intact, with angular deformity less than 20 degrees , a residual spinal
canal greater than 50% of normal, and an anterior body height exceeding 50% of
the posterior height. Surgical intervention is generally indicated in patients
with partial neurological deficit, and those with severe instability.
PMID- 9637622
TI - Comparison of hydroxyapatite granules to autogenous bone graft in fusion cages in
a goat model.
AB - BACKGROUND: With the increased use of fusion cages to achieve lumbar
intervertebral fusion, the question arises as to the potential for bone ingrowth
from the host bone through the entire cage. Is it even necessary to have an
autogenous graft to achieve total bone incorporation? METHODS: Nine adult male
goats had fusion cages implanted into three vertebral bodies. The design was
Surgical Dynamics/Ray Fusion Cage, measuring 21 mm x 14 mm. In each animal, one
fusion cage was filled with autogenous graft, one with hydroxyapatite, porous
granules, and the other with nonporous granules. Amount of new bone formation was
determined by backscatter electron microscopy at 3 months post implantation in
all animals. RESULTS: The histologic section shows that there was total
incorporation in all specimens at 3 months. There was slightly more new bone
(43%) with the nonporous granules compared with the porous granules (35%). The
amount of residual void space was about the same in all specimens, indicating
that the amount of new bone formation was similar and not statistically different
in cages filled with hydroxyapatite granules versus granules of autogenous bone.
CONCLUSION: This study confirms that total incorporation by ingrowth of new bone
can be expected in fusion cages. The amount of ingrowth is about the same for
autogenous graft versus hydroxyapatite granules. Apparently, it is not necessary
to use bone graft to achieve successful bone incorporation if an acceptable
biocompatable lattice, such as hydroxyapatite granules, is used.
PMID- 9637623
TI - Fluorosis.
PMID- 9637624
TI - Neurosurgery of the peripheral nervous system: the posterior interosseous nerve
syndrome.
PMID- 9637625
TI - Computed imaging-assisted stereotactic brain biopsy: a risk analysis of 225
consecutive cases.
AB - BACKGROUND: Treatment strategies for intracranial mass lesions are most effective
when based upon histopathological diagnoses. Image-guided stereotaxy has provided
the means to sample tissue from small or deeply seated intraparenchymal lesions
with a relatively high degree of safety and accuracy. Although procedural
complications are infrequent, devastating neurological sequelae may result from
hemorrhage or direct trauma. This study was undertaken to identify factors that
may confer an increased risk of morbidity from stereotactic brain biopsy.
METHODS: Two hundred twenty-five consecutive computer-assisted stereotactic brain
biopsy procedures were reviewed. Patient age averaged 47.4 years (range, 3-84
years); gender ratio was approximately 2:1 (male:female). Pre-existing medical
conditions were identified in nearly half of the cohort. 61.3% of biopsied
lesions were lobar; the remainder (38.7%) were "deep-seated" (thalamus, basal
ganglia, pineal, hypothalamus, cerebellum, brainstem). Glial tumors accounted for
the majority (44.4%) of biopsied lesions; metastases (12.9%) and lymphoma (11.6%)
were also relatively common. Demographical, anatomical, surgical, and
histological data were compiled and putative risk factors for morbidity
identified. These variables were then subjected to univariate and logistic
regression analyses to determine their significance as independent predictors of
operative risk. RESULTS: Twelve patients suffered complications as a consequence
of the biopsy procedure (eight from hemorrhage, four from direct trauma). Major
morbidity (hemiparesis, aphasia, obtundation) occurred in eight patients (3.6%).
Three patients (1.3%) suffered minor morbidity (transient, mild neurological
deficits). One operative fatality occurred (0.4%). An increased risk of morbidity
was associated with the preoperative use of antiplatelet agents, chronic
corticosteroids, deep-seated lesions, malignant gliomas, and a greater number of
biopsy attempts (p < 0.05). Factors not conferring increased morbidity included
gender, age, pre-existing illness, extracranial malignancy, cardiac disease,
hypertension, diabetes, HIV status, and instrument used to procure the specimen.
CONCLUSIONS: Complications arising from stereotactic brain biopsy are infrequent
but can be disastrous. Operative risk is a function of several independent
variables, including lesion properties (location, histology), preoperative
pharmacological therapy (corticosteroids, antiplatelet agents), and operative
technique. This analysis suggests that the morbidity of stereotactic brain biopsy
may be minimized by risk factor modification.
PMID- 9637626
TI - Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and
cerebral blood flow--a better way of monitoring the severely injured brain?
AB - BACKGROUND: The ideal method for monitoring the acutely injured brain would
measure substrate delivery and brain function continuously, quantitatively, and
sensitively. We have tested the hypothesis that brain PO2, pCO2, and pH, which
can now be measured continuously using a single sensor, are valid indicators of
regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its
product, brain pCO2. METHODS: Twenty-five patients (Glasgow Coma Score < or = 8)
were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7,
Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain PO2,
pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies.
Regional CBF was measured around the probe, using stable xenon computed
tomography. Regression analyses and Spearman Rank tests were used for data
analysis. RESULTS: Regional CBF and mean brain PO2 were strongly correlated
(r=0.74, p=0.0001). CBF values < 18 mL/100 g/min were all accompanied by brain
PO2 < or = 26 mm Hg. The four patients with a brain PO2 < 18 mm Hg died. Brain
pCO2 and pH, however, were not correlated with CBF (r=0.36, p=0.24 and r=0.30,
p=0.43, respectively). CONCLUSIONS: Until recently, substrate supply to the
severely injured brain could only be intermittently estimated by measuring CBF.
The excellent intra-regional correlation between CBF and brain pO2, suggests that
this method does allow continuous monitoring of true substrate delivery, and
offers the prospect that measures to increase O2 delivery (e.g., increasing CBF,
CPP, perfluorocarbons etc.) can be reliably tested by brain PO2 monitoring.
PMID- 9637627
TI - Targeted studies as a learning tool in outcomes assessment.
AB - Authors discuss the need for increased analytical skills in the current medical
environment and suggest a method which combines the use of targeted studies and
Internet communication as part of graduate medical education. Advantages of such
a program include involvement of the private sector in clinical outcome studies,
improvements in the design of clinical studies and publications and the early
development of skills in interpreting and evaluating literature. A further goal
would be the development of an understanding of the principles underlying, to the
extent that it is possible, unbiased assessment of one's own clinical practices.
PMID- 9637628
TI - Hemorrhagic lesions causing acute sensorineural hearing loss.
PMID- 9637629
TI - Implications of evolving health care: changes for tertiary care specialties such
as neurosurgery: practice, teaching, and research in the future in the academic
setting.
PMID- 9637630
TI - Omental transplantation.
PMID- 9637631
TI - Bupivacaine in lumbar spine surgery.
PMID- 9637632
TI - Fast track cardiac surgery pathways: early extubation, process of care, and cost
containment.
PMID- 9637633
TI - Laryngeal reflexes: exploring terra incognita.
PMID- 9637634
TI - Halogenated anesthetics and the injured lung: clouds on the horizon?
PMID- 9637635
TI - Do shorter-acting neuromuscular blocking drugs or opioids associate with reduced
intensive care unit or hospital lengths of stay after coronary artery bypass
grafting? CABG Clinical Benchmarking Data Base Participants.
AB - BACKGROUND: The authors hypothesized that shorter-acting opioid and neuromuscular
blocking drugs would be associated with reductions in duration of intubation,
length of stay (LOS) in the intensive care unit (ICU) after tracheal extubation,
or postoperative (exclusive of ICU) LOS, and that shorter durations of intubation
would be associated with reduced ICU LOS after extubation and postoperative
(exclusive of ICU) LOS. METHODS: One-thousand ninety-four patients undergoing
primary coronary artery bypass graft surgery at 40 academic health centers were
studied. Multiple patient-related factors were included in multivariate models
for hypothesis testing. RESULTS: The duration of tracheal intubation, ICU LOS
after extubation, and postoperative (exclusive of ICU) LOS all varied
significantly by site. There was no difference between vecuronium and pancuronium
in duration of intubation, ICU LOS after extubation, or postoperative (exclusive
of ICU) LOS. Use of sufentanil rather than fentanyl was associated with a
significant (P=0.045) reduction of 1.9 h (95% CI, 0.04 to 4.1 h) in duration of
tracheal intubation but had no significant effect on ICU LOS after extubation,
total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS.
The authors' best model predicts a complex association between increasing
duration of intubation and both ICU LOS after tracheal extubation and
postoperative (exclusive of ICU) LOS, which was associated with an increase in
those measures when duration of intubation exceeded 7.3 or 3 h, respectively.
CONCLUSIONS: The LOS measures varied considerably among the institutions. Use of
shorter-acting opioid and neuromuscular blocking drugs had no association with
ICU LOS after tracheal extubation or with postoperative (exclusive of ICU) LOS.
Only when the duration of intubation exceeded threshold values was it associated
with increased LOS measures.
PMID- 9637636
TI - Early extubation following cardiac surgery in a veterans population.
AB - BACKGROUND: Early tracheal extubation is an important component of the "fast
track" cardiac surgery pathway. Factors associated with time to extubation in the
Department of Veterans Affairs (DVA) population are unknown. The authors
determined associations of preoperative risk and intraoperative clinical process
variables with time to extubation in this population. METHODS: Three hundred four
consecutive patients undergoing coronary artery bypass graft, valve surgery, or
both on a fast track clinical pathway between October 1, 1993 and September 30,
1995 at a university-affiliated DVA medical center were studied retrospectively.
After univariate screening of a battery of preoperative risk and intraoperative
clinical process variables, stepwise logistic regression was used to determine
associations with tracheal extubation < or = 10 h (early) or > 10 h (late) after
surgery. Postoperative lengths of stay, complications, and 30-day and 6-month
mortality rates were compared between the two groups. RESULTS: One hundred forty
six patients (48.3%) were extubated early; one patient required emergent
reintubation (0.7%). Of the preoperative risk variables considered, only age
(odds ratio, 1.80 per 10-yr increment) and preoperative intraaortic balloon pump
(odds ratio, 7.88) were multivariately associated with time to extubation (model
R) ("late" association is indicated by an odds ratio >1.00; "early" association
is indicated by an odds ratio <1.00). Entry of these risk variables into a second
regression model, followed by univariately significant intraoperative clinical
process variables, yielded the following associations (model R-P): age (odds
ratio, 1.86 per 10-yr increment), sufentanil dose (odds ratio, 1.54 per 1
microg/kg increment), major inotrope use (odds ratio, 5.73), platelet transfusion
(odds ratio, 10.03), use of an arterial graft (odds ratio, 0.32), and fentanyl
dose (odds ratio, 1.45 per 10-microg/kg increment). Time of arrival in the
intensive care unit after surgery was also significant (odds ratio, 1.42 per 1-h
increment). Intraoperative clinical process variables added significantly to
model performance (P < 0.001 by the likelihood ratio test). CONCLUSIONS: In this
population, early tracheal extubation was accomplished in 48% of patients.
Intraoperative clinical process variables are important factors to be considered
in the timing of postoperative extubation after fast track cardiac surgery.
PMID- 9637637
TI - Upper airway reflexes during a combination of propofol and fentanyl anesthesia.
AB - BACKGROUND: The effects of intravenous anesthetics on airway protective reflexes
have not been fully explored. The purpose of the present study was to
characterize respiratory and laryngeal responses to laryngeal irritation during
increasing doses of fentanyl under propofol anesthesia. METHODS: Twenty-two
female patients anesthetized with propofol and breathing through the laryngeal
mask airway were randomly allocated to three groups: (1) eight patients who
received cumulative total doses of 200 microg fentanyl given in the form of two
doses of 50 microg and one dose of 100 microg spaced 6 min under mechanical
controlled ventilation while end-tidal carbon dioxide tension (PCO2) was
maintained at 38 mmHg (fentanyl-controlled ventilation group), (2) eight patients
who received cumulative total doses of 200 microg fentanyl while breathing
spontaneously while end-tidal PCO2 was allowed to increase spontaneously
(fentanyl-spontaneous ventilation group), and (3) six spontaneously breathing
patients who were anesthetized with propofol alone (propofol group). The
laryngeal mucosa of each patient was stimulated by spraying the cord with
distilled water, and the evoked responses were assessed by analyzing the
respiratory variables and endoscopic images. RESULTS: Before administration of
fentanyl, laryngeal stimulation caused vigorous reflex responses, such as
expiration reflex spasmodic panting, cough reflex, and apnea with laryngospasm.
Increasing doses of fentanyl reduced the incidences of all these responses,
except for apnea with laryngospasm, in a dose-related manner in both the fentanyl
controlled ventilation and the fentanyl-spontaneous ventilation groups. Detailed
analysis of endoscopic images revealed several characteristics of laryngeal
behavior during the airway reflex responses. CONCLUSION: Incremental doses of
fentanyl depress airway reflex responses in a dose-related manner, except for
apnea with laryngospasm.
PMID- 9637638
TI - Intravenous remifentanil: placental transfer, maternal and neonatal effects.
AB - BACKGROUND: Remifentanil has not been studied in obstetric patients. This study
evaluates the placental transfer of remifentanil and the neonatal effects when
administered as an intravenous infusion. METHODS: Nineteen parturients underwent
nonemergent cesarean section with epidural anesthesia and received 0.1 microg kg(
1) x min(-1) remifentanil intravenously, which was continued until skin closure.
Maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood
samples were obtained at delivery for analysis of drug concentrations of
remifentanil, its metabolite, and blood gases. Maternal vital signs were
monitored continuously, and pain and sedation levels were assessed
intermittently. Apgar scores were obtained at 1, 5, 10, and 20 min, and Neonatal
and Adaptive Capacity Scores were noted 30 and 60 min after delivery. Parturients
and newborns were observed for at least 24 h after surgery for side effects.
RESULTS: The means and SDs of UV:MA and UA:UV ratios for remifentanil were 0.88+/
0.78 and 0.29+/-0.07, respectively. Mean clearance was 93 ml x min(-1) kg(-1).
The mean UV:MA and UA:MV ratios for remifentanil acid were 0.56+/-0.29 and 1.23+/
0.89, respectively. The mean MA (remifentanil acid):MA (remifentanil) ratio was
2.92+/-3.65. There were no adverse effects on the neonates, but there was a
sedative effect and respiratory depressant effect on the mothers. CONCLUSIONS:
Remifentanil crosses the placenta but appears to be rapidly metabolized,
redistributed, or both. Maternal sedation and respiratory changes occur, but
without adverse neonatal or maternal effects.
PMID- 9637639
TI - Prophylactic angiotensin II infusion during spinal anesthesia for elective
cesarean delivery.
AB - BACKGROUND: Angiotensin II may prove useful in treating regional anesthesia
induced hypotension in obstetric patients, because it causes less uterine
vasoconstriction than do other vasoconstrictor drugs (such as phenylephrine).
This study compared (1) maternal blood pressure and heart rate and (2) fetal
status at delivery in parturients given either prophylactic angiotensin II or
ephedrine infusion during spinal anesthesia for elective cesarean delivery.
METHODS: Fifty-four women were randomized to receive either angiotensin II or
ephedrine infusion intravenously during spinal anesthesia for elective cesarean
section delivery. Simultaneous with subarachnoid injection, infusion of
angiotensin II (2.5 microg/ml) or ephedrine (5 mg/ml) was initiated at 10 ng x
kg(-1) x min(-1) and 50 microg x kg(-1) x min(-1), respectively. The rate of each
infusion was adjusted to maintain maternal systolic blood pressure at 90-100% of
baseline. RESULTS: Cumulative vasopressor doses (mean+/-SD) through 10, 20, and
30 min were 150+/-100, 310+/-180, and 500+/-320 ng/kg in the angiotensin group
and 480+/-210, 660+/-390, and 790+/-640 microg/kg in the ephedrine group.
Maternal heart rate was significantly higher (P < 0.001) during vasopressor
infusion in the ephedrine group than in the angiotensin group. Umbilical arterial
and venous blood pH and base excess were all significantly higher (P < 0.05) in
the angiotensin group than in the ephedrine group. CONCLUSIONS: Angiotensin II
infusion maintained maternal systolic blood pressure during spinal anesthesia
without increasing maternal heart rate or causing fetal acidosis.
PMID- 9637640
TI - A comparison of the posterior versus lateral approaches to the block of the
sciatic nerve in the popliteal fossa.
AB - BACKGROUND: The main disadvantage of the posterior approach to the block of the
sciatic nerve in the popliteal fossa (popliteal block [PB]) is the need to place
the patient in the prone position. In this study, the authors examined the
clinical utility of a recently described lateral approach to PB that is performed
with the patient in the supine position, and they compared its ability to provide
reliable surgical anesthesia with that of the posterior approach. METHODS: Fifty
patients undergoing surgery of a lower extremity were randomized to receive the
PB using either the lateral (n=25) or the posterior approach (n=25). With both
techniques, 40 ml 1.5% alkalinized mepivacaine with 1:200,000 epinephrine were
injected on successful nerve localization using low current output nerve
stimulation. RESULTS: There were no differences in American Society of
Anesthesiologists physical status or demographic data between the groups (ASA
status, I-III; mean age, 50+/-15 yr; 27 men, 23 women). All patients had good
intraoperative analgesia, except one in the lateral group, who reported pain
outside the distribution of the sciatic nerve. CONCLUSIONS: Although blockade
using the lateral approach took longer to accomplish, both techniques resulted in
clinically acceptable anesthesia in the distribution of the sciatic nerve.
PMID- 9637641
TI - Causes and prediction of maldistribution during continuous spinal anesthesia with
isobaric or hyperbaric bupivacaine.
AB - BACKGROUND: Many cases of cauda equina syndrome after maldistribution of local
anesthetics during continuous spinal anesthesia have been reported. In
experiments, a caudad route of catheter travel and the use of hyperbaric agents
have been shown to induce these limited blocks. The aim of this clinical study
was to verify this hypothesis and seek a predictive factor for the
maldistribution of bupivacaine. METHOD: Continuous spinal anesthesia via a 19
gauge end port spinal catheter was performed in 80 elderly patients randomly
assigned to receive either isobaric or hyperbaric solutions. Successive
injections of 2.5 mg bupivacaine were performed at 5-min intervals until a
sensory level at or cranial to T8 was obtained. Maldistribution was defined by a
sensory level caudal to T12 despite a total dose of 17.5 mg of either isobaric or
hyperbaric bupivacaine. After surgery, all catheters were injected with contrast
media and examined radiographically. RESULTS: The frequency of maldistribution
was not significantly different in the isobaric and hyperbaric groups. A caudally
oriented catheter tip was found to be a major cause of maldistribution (P < 10(
5)). A thoracic sensory level could be reached in all patients presenting a
limited block by simply changing the baricity of the bupivacaine, the position of
the patient, or both. The sensory level obtained 10 min after the first injection
of 2.5 mg isobaric or hyperbaric bupivacaine was found to be a predictive factor
of maldistribution. CONCLUSIONS: Hyperbaric solutions do not appear to be a
clinical factor in the development of limited block. The principle factor causing
the maldistribution of bupivacaine is the caudal orientation of the tip of the
end-hole catheter rather than its level or the route of catheter travel.
PMID- 9637642
TI - Labor epidural analgesia without an intravascular "test dose".
AB - BACKGROUND: This study prospectively evaluated the ability of aspiration to
detect intravascular placement of multiple-orifice epidural catheters. METHODS:
Multiple-orifice, 20-gauge epidural catheters were inserted in 1,029 laboring
women. Catheters were observed and aspirated for blood or cerebrospinal fluid
before they were tested with 2 ml local anesthetic. If the results of this test
were negative (no spinal anesthesia), the authors induced and maintained labor
analgesia with a dilute local anesthetic and opioid solution. Patients with
bilateral sensory change and effective labor analgesia had a "positive" epidural
catheter. Women with unilateral block, inadequate analgesia despite some sensory
change or those who delivered before being adequately assessed had "equivocal"
catheters. Patients with neither analgesia nor sensory change had "negative"
catheters. RESULTS: Aspiration and observation identified 60 intravenously placed
catheters. Six catheters, which were placed initially in a blood vessel, were
withdrawn until aspiration was negative, and then the anesthetic was infused.
Four of these catheters were positive and two were still positioned
intravascularly. Two other catheters may have been intravenously placed despite
negative results of aspiration. The incidence of false-negative results of
aspiration was 0 to 2 of 1,085 (upper limit of 95% CI, 0.2% to 0.4%). No patient
showed any signs or symptoms of local anesthetic toxicity. CONCLUSIONS: Under the
conditions of this study, which include using multiple-orifice catheters and
dilute solutions of local anesthetic and opioid, aspiration and incremental drug
injection alone safeguard against the risks of intravenously positioned local
anesthetics. These results should not be extrapolated to other clinical settings
without further study.
PMID- 9637643
TI - Treatment of incomplete analgesia after placement of an epidural catheter and
administration of local anesthetic for women in labor.
AB - BACKGROUND: Approximately 15% of women still have pain after placement of an
epidural catheter and administration of local anesthetic for labor analgesia. Two
techniques frequently used to treat this pain were compared: (1) withdrawal of
the catheter 1 cm and repeated dosing with additional local anesthetic, and (2)
repeated dosing with additional local anesthetic without any catheter
manipulation. METHODS: Fifteen minutes after placement of a multiple-orifice
epidural catheter 5 cm into the epidural space and administration of 13 ml 0.25%
bupivacaine to the parturient in labor, the adequacy of analgesia was assessed.
All women who had incomplete analgesia were randomized (first intervention) to
receive an additional 5 ml 0.25% bupivacaine (local-anestheticonly group) or to
receive 5 ml 0.25% bupivacaine after first withdrawing the epidural catheter 1 cm
(catheter-manipulation group). If after 15 min the woman still had pain, then
(second intervention) the catheter was withdrawn 1 cm and an additional 5 ml
0.25% bupivacaine was administered to the local-anesthetic-only group, whereas 5
ml 0.25% bupivacaine was given to the catheter-manipulation group without further
catheter manipulation. The success rate of the second intervention was assessed
15 min later. RESULTS: Seventy-eight women were enrolled in the study, 39 to each
group. In the local-anesthetic-only group, 29 (74%) women were successfully
treated with the first intervention and the remaining 10 (100%) were successfully
treated with the second intervention. In the catheter-manipulation group, 30
(77%) were successfully treated with the first intervention and 7 (100%; 2
patients were not studied because of investigator error) were successfully
treated with the second intervention (P=NS). CONCLUSIONS: Administration of
additional local anesthetic without first withdrawing the epidural catheter will
effectively treat most women for whom analgesia is incomplete after the placement
of an epidural catheter during labor.
PMID- 9637644
TI - Effects of oral clonidine on heart rate changes after neostigmine-atropine
administration.
AB - BACKGROUND: Clonidine reduces heart rate (HR) responses to atropine, whereas
neostigmine causes bradycardia. This study was designed to determine whether
clonidine premedication would reduce tachycardia after neostigmine-atropine
administration. METHODS: Fifty adult patients without cardiovascular disorders
who were scheduled for elective surgeries were randomly assigned to receive
approximately 5 microg/kg (oral clonidine clonidine group, n=25) or no clonidine
(control group, n=25) 90 min before induction of general anesthesia. After
tracheal intubation, anesthesia was maintained with N2O and 12% isoflurane in
oxygen while patients were paralyzed with vecuronium and mechanically ventilated.
When surgeries were completed, adequate spontaneous respiration, responses to
verbal commands, and sustained tetanus by stimulating the ulnar nerve were
confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg
neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s
under stable hemodynamic condition (systolic blood pressure and HR within +/-5%
of preceding values), and blood pressure and HR were measured noninvasively at 1
min intervals for 10 min. RESULTS: Increases in HR in the clonidine group were
significantly less 1-4 min after neostigmine--atropine injections compared with
HR values in the control group. A maximum increase in HR of the clonidine group
was also significantly less than the control group (15+/-7 vs. 23+/-10 beats/min;
means+/-SD), whereas absolute values of mean blood pressure were similar. Severe
bradycardia (HR < 50 beats/min) developed in no patients in either group.
CONCLUSIONS: Premedication with 5 microg/kg oral clonidine attenuates the initial
increases in HR without subsequent decreases in HR.
PMID- 9637645
TI - Tissue heat content and distribution during and after cardiopulmonary bypass at
31 degrees C and 27 degrees C.
AB - BACKGROUND: Afterdrop following cardiopulmonary bypass results from
redistribution of body heat to inadequately warmed peripheral tissues. However,
the distribution of heat between the thermal compartments and the extent to which
core-to-peripheral redistribution contributes to post-bypass hypothermia remains
unknown. METHODS: Patients were cooled during cardiopulmonary bypass to
nasopharyngeal temperatures near 31 degrees C (n=8) or 27 degrees C (n=8) and
subsequently rewarmed by the bypass heat exchanger to approximately 37.5 degrees
C. A nasopharyngeal probe evaluated core (trunk and head) temperature and heat
content. Peripheral compartment (arm and leg) temperature and heat content were
estimated using fourth-order regressions and integration over volume from 19
intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot
temperature. RESULTS: In the 31 degrees C group, the average peripheral tissue
temperature decreased to 31.9+/-1.4 degrees C (means+/-SD) and subsequently
increased to 34+/-1.4 degrees C at the end of bypass. The core-to-peripheral
tissue temperature gradient was 3.5+/-1.8 degrees C at the end of rewarming, and
the afterdrop was 1.5+/-0.4 degrees C. Total body heat content decreased 231+/-93
kcal. During pump rewarming, the peripheral heat content increased to 7+/-27 kcal
below precooling values, whereas the core heat content increased to 94+/-33 kcal
above precooling values. Body heat content at the end of rewarming was thus 87+/
42 kcal more than at the onset of cooling. In the 27 degrees C group, the average
peripheral tissue temperature decreased to a minimum of 29.8 +/-1.7 degrees C and
subsequently increased to 32.8+/-2.1 degrees C at the end of bypass. The core-to
peripheral tissue temperature gradient was 4.6+/-1.9 degrees C at the end of
rewarming, and the afterdrop was 2.3+/-0.9 degrees C. Total body heat content
decreased 419+/-49 kcal. During pump rewarming, core heat content increased to
66+/-23 kcal above precooling values, whereas peripheral heat content remained
70+/-42 kcal below precooling values. Body heat content at the end of rewarming
was thus 4+/-52 kcal less than at the onset of cooling. CONCLUSIONS: Peripheral
tissues failed to fully rewarm by the end of bypass in the patients in the 27
degrees C group, and the afterdrop was 2.3+/-0.9 degrees C. Peripheral tissues
rewarmed better in the patients in the 31 degrees C group, and the afterdrop was
only 1.5+/-0.4 degrees C.
PMID- 9637646
TI - Epidural fentanyl produces labor analgesia by a spinal mechanism.
AB - BACKGROUND: The purpose of this study was to determine if epidural fentanyl
produces analgesia in laboring patients by a primary spinal or supraspinal
action. METHODS: Fifty-four parturients were randomized to receive epidural
0.125% bupivacaine plus one of three treatments: epidural saline-intravenous
saline, epidural fentanyl (20 microg/h)-intravenous saline, or epidural saline
intravenous fentanyl (20 microg/h). The study treatments were administered by
continuous infusion, whereas epidural bupivacaine use was patient controlled.
RESULTS: Epidural bupivacaine use was significantly reduced by epidural (11.5+/
4.6 ml/h) but not by intravenous fentanyl (15.9+/-4.5 ml/h) compared with saline
control (16+/-5.9 ml/ h). Analgesia characteristics and side effects were similar
among groups. CONCLUSIONS: Low-dose epidural infusions of fentanyl produce labor
analgesia by a primary spinal action.
PMID- 9637647
TI - Desflurane increases pulmonary alveolar-capillary membrane permeability after
aortic occlusion-reperfusion in rabbits: evidence of oxidant-mediated lung
injury.
AB - BACKGROUND: Pulmonary injury occurs after vascular surgery, with xanthine oxidase
(an oxidant generator) released from reperfusing liver and intestines mediating a
significant component of this injury. Because halogenated anesthetics have been
observed to enhance oxidant-mediated injury in vitro, the authors hypothesized
that desflurane would increase alveolar-capillary membrane permeability mediated
by circulating xanthine oxidase after thoracic occlusion and reperfusion.
METHODS: Rabbits were assigned to one of five groups: aorta occlusion groups
administered desflurane (n=14), desflurane and tungstate (xanthine oxidase
inactivator, n=12), fentanyl plus droperidol (n=13), and two sham-operated groups
(desflurane, n=7 and fentanyl plus droperidol, n=7). Aortic occlusion was
maintained for 45 min with a balloon catheter, followed by 3 h of reperfusion.
Alveolar-capillary membrane permeability was assessed by measurement of
bronchoalveolar lavage fluid protein. Xanthine oxidase activity was determined in
plasma and lung tissue. Ascorbic acid content (an antioxidant) was determined in
lung tissue. RESULTS: Desflurane was associated with significantly increased
alveolar-capillary membrane permeability after aortic occlusion-reperfusion when
compared with the fentanyl plus droperidol anesthesia or sham-operated groups (P
< 0.05). Inactivation of xanthine oxidase abrogated the alveolar-capillary
membrane compromise associated with desflurane. Although significantly greater
than for sham-operated animals, plasma xanthine oxidase activities released after
aortic occlusion-reperfusion were not different between the two anesthetics.
There were no anesthetic-associated differences in lung tissue xanthine oxidase
activity. However, desflurane anesthesia resulted in a significant reduction in
lung ascorbic acid after aortic occlusion-reperfusion compared with the sham
operated animals. CONCLUSIONS: Desflurane anesthesia increased xanthine oxidase
dependent alveolar-capillary membrane compromise after aortic occlusion
reperfusion in concert with depletion of a key tissue antioxidant.
PMID- 9637648
TI - Nonanesthetic volatile drugs obey the Meyer-Overton correlation in two molecular
protein site models.
AB - BACKGROUND: Nonanesthetic volatile compounds fail to inhibit movement in response
to noxious stimulation at concentrations predicted to induce anesthesia from
their oil-water partitioning. Thus they represent tools to determine whether
molecular models behave like the targets that mediate in vivo anesthetic actions.
The effects of volatile anesthetics and nonanesthetics were examined in two
experimental models in which anesthetics interact directly with proteins: the
pore of the nicotinic acetylcholine receptor and human serum albumin. METHODS:
Wild-type mouse muscle nicotinic receptors and receptors containing pore
mutations (alphaS252I + betaT263I) were studied electrophysiologically in
membrane patches from Xenopus oocytes. Patch currents evoked by brief pulses of
acetylcholine were measured in the presence of enflurane and two nonanesthetics,
1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane. Nonanesthetic
interactions with human serum album were assessed by quenching of intrinsic
protein fluorescence. RESULTS: Both anesthetic and nonanesthetic volatile
compounds inhibited wild-type and alphaS252I + betaT263I mutant nicotinic
channels but displayed different selectivity for open versus resting receptor
states. Median inhibitory concentrations (IC50s) in wild-type nicotinic receptors
were 870+/-20 microM for enflurane, 37+/-3 microM for 1,2
dichlorohexafluorocylcobutane, and 11.3+/-5.6 microM for 2,3
dichlorooctafluorobutane. For all three drugs, ratios of wild-type IC50s to
mutant IC50mut ranged from 7-10, and ratios of wild-type IC50s to predicted
anesthetic median effective concentrations (EC50s) ranged from 1.8-2.3. 1,2
Dichlorohexafluorocyclobutane quenched human serum albumin with an apparent
dissociation constant (Kd) of 160+/-11 microM. The ratios of dissociation
constants to predicted EC50s for the nonanesthetics were within a factor of two
of the dissociation constant:EC50 ratios calculated for halothane and chloroform
from previous published results. CONCLUSIONS: In two models in which anesthetics
bind to protein sites, both anesthetic and nonanesthetic volatile drugs cause
similar steady state effects with potencies that are predicted by hydrophobicity.
These protein sites do not sterically discriminate between anesthetic and
nonanesthetic drugs. However, differential state-selective actions on ion channel
targets may underlie the distinct in vivo effects of anesthetics and
nonanesthetics.
PMID- 9637649
TI - The effects of extracellular pH with and without bicarbonate on intracellular
procaine concentrations and anesthetic effects in crayfish giant axons.
AB - BACKGROUND: The potentiating effect of sodium bicarbonate on local anesthetic
action is attributed to two mechanisms: (1) an increase in the un-ionized local
anesthetic due to extracellular alkalinization, and (2) an accelerated conversion
of local anesthetic from un-ionized to ionized form with intracellular
acidification caused by bicarbonate. To evaluate these hypotheses, the
intracellular pH, intracellular ionized procaine concentration, and evoked action
potentials were measured in crayfish giant axons. METHODS: In all measurements,
axon preparations from crayfish were perfused extracellularly for 15 min with
either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free
solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH
was measured using a pH-sensitive microelectrode. Intracellular anesthetic
concentration was measured using a specially designed procaine-sensitive
microelectrode with each of three solutions containing 1 mM procaine
hydrochloride. Membrane potential was measured and, as an index of anesthetic
action, the dV/dt of evoked action potential was calculated during perfusion with
procaine. RESULTS: Mean intracellular pH was significantly lower in the
bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and
nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized
procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08
mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6
(0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and
nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately
coincident with the mean intracellular procaine concentration in each solution.
CONCLUSION: The presence of bicarbonate or extracellular alkalinization increased
the intracellular concentration of ionized procaine and the anesthetic effect.
PMID- 9637650
TI - The effects of epidural morphine on cardiac and renal sympathetic nerve activity
in alpha-chloralose-anesthetized cats.
AB - BACKGROUND: Epidural morphine yields postoperative pain relief and hemodynamic
stability. However, the effects of epidural morphine on sympathetic tone are
unclear. This study was designed to elucidate the effects of epidural morphine on
cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement
in anesthetized cats. METHODS: Thirty mongrel cats anesthetized with alpha
chloralose were randomly assigned to one of the following five groups: control
(0.2 ml/kg thoracic epidural normal saline; n=5); thoracic epidural morphine
(n=9); lumbar epidural morphine (n=6); vagotomized, sinoaortic denervated,
thoracic epidural morphine (n=5); or intravenous morphine (n=5). Mean arterial
pressure (MAP), heart rate (HR), CSNA, and RSNA were measured 0, 15, 30, 60, 90,
and 120 min after saline or morphine (200 microg/kg) administration and 15 min
after reversal with 200 microg naloxone given intravenously. RESULTS: In the
control group, no changes in measured variables were found after either thoracic
epidural saline or intravenous naloxone. Thoracic and lumbar epidural morphine
both significantly reduced MAP, HR, CSNA, and RSNA 30 through 120 min after
morphine administration (P < 0.05). These changes were reversed by intravenous
naloxone. Changes after thoracic epidural morphine administration in vagotomized,
baroreceptor-denervated cats were similar to those in intact cats. Intravenous
morphine produced no significant changes except for a decrease in MAP, which was
reversed by intravenous naloxone. CONCLUSION: In contrast to intravenous
morphine, thoracic and lumbar epidural morphine both inhibited cardiac and renal
sympathetic nerve activity and consequently reduced MAP and HR in alpha
chloralose anesthetized cats.
PMID- 9637651
TI - Effect of propofol on norepinephrine-induced increases in [Ca2+]i and force in
smooth muscle of the rabbit mesenteric resistance artery.
AB - BACKGROUND: Propofol (2,6-diisopropylphenol) possesses vasodilating activity in
vivo and in vitro. The propofol-induced relaxation of agonist-induced
contractions in small resistance arteries has not been clarified. METHODS: The
effect of propofol was examined on the contractions induced by norepinephrine and
high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The
effects of propofol on the [Ca2+]i mobilization induced by norepinephrine and
high K+ were studied by simultaneous measurement of [Ca2+]i using Fura 2 and
isometric force in ryanodine-treated strips. RESULTS: Propofol attenuated the
contractions induced by high K+ and norepinephrine, the effect being greater on
the high K+-induced contraction than on the norepinephrine-induced contraction.
In Ca2+-free solution, norepinephrine produced a transient contraction resulting
from the release of Ca2+ from storage sites that propofol attenuated. In
ryanodine-treated strips, propofol increased the resting [Ca2+]i but attenuated
the increases in [Ca2+]i and force induced by both high K+ and norepinephrine. In
the presence of nicardipine, propofol had no inhibitory action on the residual
norepinephrine-induced [Ca2+]i increase, whereas it still modestly increased
resting [Ca2+]i, as in the absence of nicardipine. CONCLUSIONS: In smooth muscle
of the rabbit mesenteric resistance artery, propofol attenuates norepinephrine
induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx
through L-type Ca2+ channels. Propofol also increased resting [Ca2+]i, possibly
as a result of an inhibition of [Ca2+]i removal mechanisms. These results may
explain in part the variety of actions seen with propofol in various types of
vascular smooth muscle.
PMID- 9637652
TI - In vitro hypothermia enhances platelet GPIIb-IIIa activation and P-selectin
expression.
AB - BACKGROUND: A clinical bleeding diathesis is associated with hypothermia.
Inhibition of platelet reactivity is the purported cause of this coagulopathy
despite inconsistent evidence to support this hypothesis. To clarify the effect
of temperature on intrinsic platelet function, platelet GPllb-IIIa activation and
P-selectin expression were assessed under normothermic and hypothermic conditions
in vitro. METHODS: Blood was obtained by venipuncture from healthy volunteers.
Platelet activation was assessed by aggregometry and by cytometric analysis of
platelet binding of fibrinogen, PAC-1, and P-selectin antibodies. Measurements
were made at normothermia (37 degrees C), moderate hypothermia (33 degrees C),
and profound hypothermia (22 degrees C) after stimulating samples with adenosine
diphosphate (ADP), collagen, or thrombin receptor activating peptide. RESULTS:
Agonist-induced platelet aggregation and fibrinogen binding were significantly
greater at 22 degrees C and 33 degrees C than at 37 degrees C. Platelet
fibrinogen binding values to 20 micro M ADP were 23,400, 14,300, and 9,700
molecules/platelet at 22 degrees C, 33 degrees C, and 37 degrees C, respectively.
The aggregation responses of platelets that were cooled and rewarmed were
indistinguishable from those of platelets maintained at 37 degrees C throughout
the study. Platelet binding of PAC-1 and P-selectin antibodies was greater under
hypothermic conditions. CONCLUSIONS: Aggregation, fibrinogen binding, PAC-1
binding, and P-selectin antibody binding studies showed that platelet GPIIb-IIIa
activation and alpha-granule release were enhanced at hypothermic temperatures.
Thus hypothermia appears to increase the ability of platelets to respond to
activating stimuli. The coagulopathy associated with hypothermia is not likely to
be the result of an intrinsic defect in platelet function.
PMID- 9637653
TI - Rebound swelling of astroglial cells exposed to hypertonic mannitol.
AB - BACKGROUND: Mannitol is widely used in anesthesia and critical care medicine.
Although its clinical effects were originally attributed to osmotic dehydration
of brain cells, other mechanisms have also been proposed. Osmotic dehydration of
astroglial cells is opposed by powerful volume-regulating mechanisms that involve
inward transport of electrolytes. These mechanisms have been studied previously
by exposing cells to hypertonic saline gradients. Because of its potential
clinical relevance, the volume response of astroglial cells exposed to hypertonic
mannitol was investigated. METHODS: Rat C6 glioma cells were cultured to
confluence, and their volume behavior was observed by laser light scattering.
After equilibration at physiologic temperature and pH, cells were abruptly
exposed to hypertonic mannitol solutions. In separate experiments, C6 cells were
exposed to hypertonic solutions containing radiolabeled mannitol, and its
cellular uptake was determined. RESULTS: Hypertonic mannitol exposure produced
initial cell shrinkage followed by rapid volume recovery and rebound swelling.
The rebound swelling was similar in magnitude to the initial maximal shrinkage.
For +40 mOsm and +70 mOsm mannitol challenges, mean volume recovery was 184+/-31%
and 227+/-62%, respectively (where full recovery to baseline volume = 100%).
Rebound swelling was substantially inhibited by furosemide. When exposed to
mannitol in varying concentrations, uptake was linear, ranging from 82+/-7
nmol/mg to 406+/-26 nmol/mg protein. After 5 min, estimated intracellular
concentrations of mannitol were similar to extracellular concentrations.
CONCLUSIONS: Unlike hypertonic saline, hypertonic mannitol exposure produces
rebound cell swelling. Cellular penetration of mannitol appears to account for
much of this phenomenon. The clinical implications of these observations remain
to be determined.
PMID- 9637654
TI - Effects of small concentrations of volatile anesthetics on action potential
firing of neocortical neurons in vitro.
AB - BACKGROUND: Volatile general anesthetics depress neuronal activity in the
mammalian central nervous system and enhance inhibitory Cl- currents flowing
across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The
extent to which an increase in GABA(A)-mediated synaptic inhibition contributes
to the decrease in neuronal firing must be determined, because many further
effects of these agents have been reported on the molecular level. METHODS: The
actions of halothane, isoflurane, and enflurane on the firing patterns of single
neurons were investigated by extracellular recordings in organotypic slice
cultures derived from the rat neocortex. RESULTS: Volatile anesthetics depressed
spontaneous action potential firing of neocortical neurons in a concentration
dependent manner. The estimated median effective concentration (EC50) values were
about one half the EC50 values for general anesthesia. In the presence of the
GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane,
isoflurane, and enflurane in reducing the discharge rates were diminished by 48
65%, indicating that these drugs act via the GABA(A) receptor. CONCLUSIONS:
Together with recent investigations, our results provide evidence that halothane,
isoflurane, and enflurane reduced spontaneous action potential firing of
neocortical neurons in cultured brain slices mainly by increasing GABA(A)
mediated synaptic inhibition. At concentrations, approximately one half the EC50
for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated
synaptic inhibition about twofold, thus decreasing spontaneous action potential
firing by half.
PMID- 9637655
TI - Halothane decreases Na,K-ATPase, and Na channel activity in alveolar type II
cells.
AB - BACKGROUND: Halothane alters surfactant biosynthesis and metabolism of alveolar
type II cells. In addition to synthesizing surfactant, alveolar type II cells
actively transport sodium (Na) from the alveolar space to the interstitium. Na
enters the cells through amiloride-sensitive Na channels or Na cotransporters and
is extruded by a Na pump. The purpose of this study was to examine the effects of
halothane on Na transport activities. METHODS: Epithelial type II cells from
adult rat lungs were exposed to halothane concentrations of 1, 2, and 4% from 0.5
4 h. In some experiments, cells that were exposed to 1% halothane for 1 h were
allowed to recover after replacement of the medium for 15 and 30 min. Na
transport was then evaluated by direct measurement of radiolabeled ions uptake.
In addition, the effects of halothane were assessed in the absence of
extracellular calcium (Ca) with or without 1,2-bis(2-aminophenoxy)ethane
N,N,N',N'-tetraacetic acid, an intracellular Ca chelating agent. RESULTS:
Exposure of epithelial type II cells to halothane reduced the activity of sodium,
potassium-adenosine triphosphatase, and amiloride-sensitive Na channels, whereas
Na cotransporters were unchanged. The decrease in sodium, potassium-adenosine
triphosphatase activity was maximal for 30 min of exposure and reached 50, 42,
and 56% for halothane concentrations of 1, 2, and 4%, respectively, and did not
change for longer exposure times. This effect was not prevented by either the
absence of extracellular Ca or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
tetraacetic acid pretreatment. Exposure for 45 min to 1% halothane also decreased
Na channel activity by 46%. These effects were completely reversible after 30 min
of recovery. CONCLUSIONS: Sodium, potassium-adenosine triphosphatase, and
amiloride-sensitive Na channel activities are impaired by halothane in alveolar
type II cells in vitro. This inhibition could reduce transepithelial Na
transport.
PMID- 9637656
TI - Cerebrovascular relaxation responses to endothelium-dependent and -independent
vasodilators after normothermic and hypothermic cardiopulmonary bypass in the
rabbit.
AB - BACKGROUND: Cardiopulmonary bypass causes activation of leukocytes and increased
concentrations of proinflammatory mediators, which may result in endothelial
dysfunction. Because hypothermia attenuates many inflammatory processes, the
authors hypothesized that hypothermic cardiopulmonary bypass would be associated
with better endothelial function than normothermic cardiopulmonary bypass.
METHODS: Isoflurane-anesthetized New Zealand White rabbits were randomized to
undergo 90 min of either normothermic (37 degrees C, n=9) or hypothermic (27
degrees C, n=9) cardiopulmonary bypass with terminal rewarming. A third group
served as anesthetized normothermic non-cardiopulmonary bypass surgical controls
(n=8). Basilar artery and descending thoracic aorta were isolated from each
animal. In vitro vessel relaxation responses to increasing concentrations of
acetylcholine (which induces endothelial release of nitric oxide) and
nitroprusside (which provides exogenous nitric oxide) were measured in
phenylephrine-precontracted vessel rings. RESULTS: There were no differences in
vessel relaxation responses between normothermic and hypothermic cardiopulmonary
bypass groups in basilar artery or aorta. In contrast, basilar arteries from non
cardiopulmonary bypass controls had increased relaxation responses to both
acetylcholine (P=0.004) and nitroprusside (P=0.031) compared with the pooled
cardiopulmonary bypass animal data. CONCLUSIONS: The authors observed no
differences in endothelial or vascular smooth muscle function between
normothermic and hypothermic cardiopulmonary bypass groups. Compared with non
cardiopulmonary bypass controls, cardiopulmonary bypass appeared to decrease
basilar artery smooth muscle relaxation in response to endogenous and exogenous
nitric oxide.
PMID- 9637657
TI - Role of the renal cysteine conjugate beta-lyase pathway in inhaled compound A
nephrotoxicity in rats.
AB - BACKGROUND: The sevoflurane degradation product compound A is nephrotoxic in rats
and undergoes metabolism to glutathione and cysteine S-conjugates, with further
metabolism by renal cysteine conjugate beta-lyase to reactive intermediates.
Evidence suggests that toxicity is mediated by renal uptake of compound A S
conjugates and metabolism by beta-lyase. Previously, inhibitors of the beta-lyase
pathway (aminooxyacetic acid and probenecid) diminished the nephrotoxicity of
intraperitoneal compound A. This investigation determined inhibitor effects on
the toxicity of inhaled compound A. METHODS: Fischer 344 rats underwent 3 h of
nose-only exposure to compound A (0-220 ppm in initial dose-response experiments
and 100-109 ppm in subsequent inhibitor experiments). The inhibitors (and
targets) were probenecid (renal organic anion transport mediating S-conjugate
uptake), acivicin (gamma-glutamyl transferase), aminooxyacetic acid (renal beta
lyase), and aminobenzotriazole (cytochrome P450). Urine was collected for 24 h,
and the animals were killed. Nephrotoxicity was assessed by histology and
biochemical markers (serum BUN and creatinine; urine volume; and excretion of
protein, glucose, and alpha-glutathione-S-transferase, a predominantly proximal
tubular cell protein). RESULTS: Compound A caused dose-related proximal tubular
cell necrosis, diuresis, proteinuria, glucosuria, and increased alpha-glutathione
S-transferase excretion. The threshold for toxicity was 98-109 ppm (294-327 ppm
h). Probenecid diminished (P < 0.05) compound A-induced glucosuria and excretion
of alpha-glutathione-S-transferase and completely prevented necrosis.
Aminooxyacetic acid diminished compound A-dependent proteinuria and glucosuria
but did not decrease necrosis. Acivicin increased nephrotoxicity of compound A,
and aminobenzotriazole had no consistent effect on nephrotoxicity of compound A.
CONCLUSIONS: Nephrotoxicity of inhaled compound A in rats was associated with
renal uptake of compound A S-conjugates and cysteine conjugates metabolism by
renal beta-lyase. Manipulation of the beta-lyase pathway elicited similar
results, whether compound A was administered by inhalation or intraperitoneal
injection. Route of administration does not apparently influence nephrotoxicity
of compound A in rats.
PMID- 9637658
TI - Chronic desipramine treatment desensitizes the rat to anesthetic and
antinociceptive effects of the alpha2-adrenergic agonist dexmedetomidine.
AB - INTRODUCTION: The effects of long-term administration of the tricyclic
antidepressant agent desipramine on the hypnotic, antinociceptive, anesthetic
sparing, and central norepinephrine turnover suppressant action of short-term
dexmedetomidine, a highly selective alpha2-adrenergic agonist, were studied in
rats. METHODS: Rats were given a 3- or 4-week course of twice daily
administration of desipramine, 10 mg/kg, or saline. The effect of a hypnotic dose
of dexmedetomidine, 250 microg/kg given intraperitoneally, on the duration of
loss of righting reflex was determined. The tail flick latency response was
determined before and after 50 microg/kg dexmedetomidine. The minimum anesthetic
concentration of halothane and the central norepinephrine turnover rate were
determined before and after administration of 30 microg/kg dexmedetomidine.
Changes in the affinity and density of the alpha2-adrenergic receptor in locus
coeruleus and spinal cord also were determined. RESULTS: Treatment with
desipramine decreased dexmedetomidine-induced loss of righting reflex duration by
67% and eliminated the antinociceptive effect of dexmedetomidine. Dexmedetomidine
produced a 55% decrease in minimum anesthetic concentration in the control group
but no reduction in desipramine-treated rats. Desipramine did not change the
receptor density or binding affinity of alpha2 receptors at the site for hypnotic
(locus coeruleus) or antinociceptive (spinal cord) responses. No decrement in the
central norepinephrine turnover rate was noted in the locus coeruleus of
dexmedetomidine after 3 weeks of treatment with desipramine. The alpha1
adrenergic antagonist prazosin at 1 or 5 mg/kg completely (minimum anesthetic
concentration reduction), almost completely (antinociceptive), or partially
(hypnotic) restored responsiveness to normal. CONCLUSIONS: These data indicate
that treatment with desipramine induces hyporesponsiveness to the hypnotic,
analgesic, and minimum anesthetic concentration-reducing, but not to the
suppression of central norepinephrine turnover, properties of dexmedetomidine.
The hyporesponsiveness appears to involve an alpha1-adrenergic mechanism.
PMID- 9637659
TI - Thiopental and methohexital depress Ca2+ entry into and glutamate release from
cultured neurons.
AB - BACKGROUND: Although barbiturates activate alpha-aminobutyric acid type A
receptors as part of their hypnotic effect, these drugs also inhibit voltage
gated calcium channels. The authors determined if barbiturates could decrease
neuronal intracellular Ca2+ transients and the resulting glutamate release.
METHODS: Neonatal rat cerebellar granule neurons were isolated and cultured on
coverslips and studied at 37 degrees C. Spectrofluorometric assays were used
during identical conditions to monitor intracellular Ca2+ with the Ca2+
sensitive fluorophore fura-2 and glutamate release by a glutamate dehydrogenase
coupled assay, which produced the reduced form of nicotinamide-adenine
dinucleotide phosphate in proportion to the amount of glutamate released. Neurons
were depolarized by a rapid increase in external [K+] from 5 to 55 mM. Control
responses were compared with those in the presence of 10, 30, and 100 microM
thiopental; 3, 10, and 30 microM methohexital; decreased external [Ca2+]; or
voltage-gated calcium channel blockers. RESULTS: Thiopental and methohexital
depressed the intracellular Ca2+ transient peak and plateau in a dose-dependent
manner, as did decreased Ca2+. The intermediate dose of either drug caused
approximately 50% decrease in peak intracellular Ca2+ and 60% decrease in
glutamate release. In the presence of specific L- and/or N-type voltage-gated
calcium channel blockade by nicardipine or omega-conotoxin-GVIA, respectively, 30
microM thiopental further decreased the intracellular Ca2+ transient. Thiopental
caused a dose-dependent decrease in glutamate release, which was proportional to
the decreased peak intracellular Ca2+. CONCLUSIONS: Thiopental and methohexital
depress the depolarization-induced increase in intracellular Ca2+ and the
accompanying glutamate release, actions which can contribute to the anesthetic
and neuronal protective effects of these drugs.
PMID- 9637661
TI - Writing successful research proposals for medical science.
PMID- 9637660
TI - A comparative evaluation of the effects of multiple vasodilators on human
internal mammary artery.
AB - BACKGROUND: Vasospasm of arterial grafts represents an unpredictable complication
of coronary artery surgery and may compromise myocardial revascularization, and
treatment is based on empirical therapy with nitroglycerin. Because of the
potential for tolerance to nitroglycerin to occur, the authors studied different
vasodilators acting through separate pathways on segments of human internal
mammary artery. METHODS: Isolated vascular rings were precontracted with
norepinephrine (1 microM), KCl, or the thromboxane A2 analogue (U46619, 10 nm).
Nitroglycerin (a nitrovasodilator), milrinone (a type III phosphodiesterase
inhibitor), papaverine (a phosphodiesterase inhibitor), prostaglandin E1, and
isradipine (a dihydropyridine calcium channel blocker) were added in a cumulative
fashion. RESULTS: The analysis of the concentration-response curves showed that
vasodilators induced 90-100% relaxation of the constricted segments with
norepinephrine or the thromboxane A2 analogue, except prostaglandin E1, which
produced 73% relaxation at maximal concentrations. The effective concentrations
of vasodilator agent that caused 50% relaxation for nitroglycerin and milrinone
were within the range of the reported therapeutic concentrations in plasma.
Isradipine was also effective at reversing receptor-mediated contraction (maximal
relaxation=100% in internal mammary artery contracted with norepinephrine;
maximal relaxation=0% in internal mammary artery contracted with the thromboxane
A2 analogue). CONCLUSIONS: Vasodilator drugs acting through multiple pathways are
effective at reversing in vitro vasoconstriction.
PMID- 9637662
TI - Malignant hyperthermia triggered coincidentally after reversal of neuromuscular
blockade in a patient from the Hmong people of Laos.
PMID- 9637663
TI - Nicorandil successfully abolished intraoperative torsade de pointes.
PMID- 9637664
TI - Paraspinal fluid extravasation from long-term epidural catheter delivery system.
PMID- 9637665
TI - Intraoperative bronchospasm induced by stimulation of the vagus nerve.
PMID- 9637666
TI - The cuffed oropharyngeal airway, a novel adjunct to the management of difficult
airways.
PMID- 9637667
TI - Use of the laryngeal mask airway in laboratory cats.
PMID- 9637668
TI - Safer endotracheal tube exchange technique.
PMID- 9637669
TI - An alternative method for conversion of a nasal to an orotracheal intubation.
PMID- 9637670
TI - Sympathectomy and redistribution are not the only causes of hypothermia.
PMID- 9637671
TI - Succinylcholine duration and critical hemoglobin desaturation in the healthy
adult.
PMID- 9637672
TI - Safety of patient-controlled intravenous meperidine.
PMID- 9637673
TI - PCA--not as effective but still a valuable method.
PMID- 9637674
TI - Preinsertion pulmonary artery catheter flushing.
PMID- 9637675
TI - A simple device to prevent back flow of blood into the intravenous line.
PMID- 9637676
TI - LIN-12/Notch signaling: lessons from worms and flies.
PMID- 9637677
TI - beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of
the beta-cell phenotype and maturity onset diabetes.
AB - To study the late beta-cell-specific function of the homeodomain protein
IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted
specifically in beta cells. These mice develop diabetes with age, and we show
that IPF1/PDX1 is required for maintaining the beta cell identity by positively
regulating insulin and islet amyloid polypeptide expression and by repressing
glucagon expression. We also provide evidence that IPF1/PDX1 regulates the
expression of Glut2 in a dosage-dependent manner suggesting that lowered
IPF1/PDX1 activity may contribute to the development of type II diabetes by
causing impaired expression of both Glut2 and insulin.
PMID- 9637678
TI - Myc activates telomerase.
AB - Telomere maintenance has been proposed as an essential prerequisite to human
tumor development. The telomerase enzyme is itself a marker for tumor cells, but
the genetic alterations that activate the enzyme during neoplastic transformation
have remained a mystery. Here, we show that Myc induces telomerase in both normal
human mammary epithelial cells (HMECs) and normal human diploid fibroblasts. Myc
increases expression of hEST2 (hTRT/TP2), the limiting subunit of telomerase, and
both Myc and hEST2 can extend the life span of HMECs. The ability of Myc to
activate telomerase may contribute to its ability to promote tumor formation.
PMID- 9637679
TI - Proteasomal regulation of nuclear receptor corepressor-mediated repression.
AB - Repression of gene transcription is a fundamental property of nuclear hormone
receptors. We report here that cell-specific repression by nuclear receptors
correlates with levels of nuclear receptor corepressor (N-CoR) protein. N-CoR
protein levels are regulated by mSiah2, a mammalian homolog of Drosophila Seven
in absentia that targets N-CoR for proteasomal degradation. mSiah2 expression is
cell-type specific and differentially regulates the repressive activities of
nuclear receptors. These findings establish targeted proteolysis of
transcriptional coregulators as a mechanism for cell-specific regulation of gene
transcription.
PMID- 9637680
TI - Seven-up, the Drosophila homolog of the COUP-TF orphan receptors, controls cell
proliferation in the insect kidney.
AB - Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in
Drosophila by a single large cell, the tip cell. It has been postulated that this
cell sends out a mitogenic signal that induces the division of neighboring cells.
The signal and the molecules that receive it have remained elusive. We show that
the COUP-TF-related nuclear orphan receptor Seven-up is a key component that
becomes induced in response to mitogenic EGF receptor signaling activity
emanating from the tip cell. Seven-up in turn is capable of regulating the
transcription of cell cycle regulators.
PMID- 9637681
TI - A novel protein complex that interacts with the vitamin D3 receptor in a ligand
dependent manner and enhances VDR transactivation in a cell-free system.
AB - Nuclear receptors transduce hormonal signals by binding directly to DNA target
sites in promoters and modulating the transcription of linked genes. Receptor
mediated transactivation appears to be potentiated in response to ligand by a
number of coactivators that may provide key interactions with components of the
transcription preinitiation complex and/or alter chromatin structure. Here, we
use the vitamin D3 receptor ligand-binding domain (VDR LBD) as an affinity matrix
to identify components of a transcriptionally active nuclear extract that
interact with VDR in response to ligand. We describe the purification of a
complex of at least 10 VDR interacting proteins (DRIPs) ranging from 65 to 250 kD
that associate with the receptor in a strictly 1,25-dihydroxyvitamin D3-dependent
manner. These proteins also appear to interact with other, but not all, nuclear
receptors, such as the thyroid hormone receptor. The DRIPs are distinct from
known nuclear receptor coactivators, although like these coactivators, their
interaction also requires the AF-2 transactivation motif of VDR. In addition, the
DRIP complex contains histone acetyltransferase activity, indicating that at
least one or more of the DRIPs may function at the level of nucleosomal
modification. However, we show that the DRIPs selectively enhance the
transcriptional activity of VDR on a naked DNA template utilizing a cell-free,
ligand-dependent transcription assay. Moreover, this activity can be specifically
depleted from the extract by liganded, but not unliganded, VDR-LBD.
Overexpression of DRIP100 in vivo resulted in a strong squelching of VDR
transactivation, suggesting the sequestration of other limiting factors,
including components of the DRIP complex. These results demonstrate the existence
of a new complex of novel functional nuclear receptor coactivators.
PMID- 9637682
TI - Kappa chain monoallelic demethylation and the establishment of allelic exclusion.
AB - Allelic exclusion in kappa light-chain synthesis is thought to result from a
feedback mechanism by which the expression of a functional kappa light chain on
the surface of the B cell leads to an intracellular signal that down-regulates
the V(D)J recombinase, thus precluding rearrangement of the other allele. Whereas
such a feedback mechanism clearly plays a role in the maintenance of allelic
exclusion, here we provide evidence suggesting that the initial establishment of
allelic exclusion involves differential availability of the two kappa alleles for
rearrangement. Analysis of kappa+ B-cell populations and of individual kappa+ B
cells that have rearranged only one allele demonstrates that in these cells,
critical sites on the rearranged allele are unmethylated, whereas the
nonrearranged allele remains methylated. This pattern is apparently generated by
demethylation that is initiated at the small pre-B cell stage, on a single
allele, in a process that occurs prior to rearrangement and requires the presence
in cis of both the intronic and 3' kappa enhancers. Taken together with data
demonstrating that undermethylation is required for rearrangement, these results
indicate that demethylation may actually underly the process of allelic exclusion
by directing the initial choice of a single kappa allele for rearrangement.
PMID- 9637683
TI - A stress response pathway from the endoplasmic reticulum to the nucleus requires
a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells.
AB - Eukaryotes respond to the presence of unfolded protein in the endoplasmic
reticulum (ER) by up-regulating the transcription of genes encoding ER protein
chaperones, such as BiP. We have isolated a novel human cDNA encoding a homolog
to Saccharomyces cerevisiae Ire1p, a proximal sensor for this signal transduction
pathway in yeast. The gene product hIre1p is a type 1 transmembrane protein
containing a cytoplasmic domain that is highly conserved to the yeast counterpart
having a Ser/Thr protein kinase domain and a domain homologous to RNase L.
However, the luminal domain has extensively diverged from the yeast gene product.
hIre1p expressed in mammalian cells displayed intrinsic autophosphorylation
activity and an endoribonuclease activity that cleaved the 5' splice site of
yeast HAC1 mRNA, a substrate for the endoribonuclease activity of yeast Ire1p.
Overexpressed hIre1p was localized to the ER with particular concentration around
the nuclear envelope and some colocalization with the nuclear pore complex.
Expression of Ire1p mRNA was autoregulated through a process that required a
functional hIre1p kinase activity. Finally, overexpression of wild-type hIre1p
constitutively activated a reporter gene under transcriptional control of the rat
BiP promoter, whereas expression of a catalytically inactive hIre1p acted in a
trans-dominant-negative manner to prevent transcriptional activation of the BiP
promoter in response to ER stress induced by inhibition of N-linked
glycosylation. These results demonstrate that hIre1p is an essential proximal
sensor of the unfolded protein response pathway in mammalian cells.
PMID- 9637684
TI - The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for
development of the sympathetic nervous system.
AB - Neuregulins (NDF, heregulin, GGF ARIA, or SMDF) are EGF-like growth and
differentiation factors that signal through tyrosine kinase receptors of the ErbB
family. Here, we report a novel phenotype in mice with targeted mutations in the
erbB2, erbB3, or neuregulin-1 genes. These three mutations cause a severe
hypoplasia of the primary sympathetic ganglion chain. We provide evidence that
migration of neural crest cells to the mesenchyme lateral of the dorsal aorta, in
which they differentiate into sympathetic neurons, depends on neuregulin-1 and
its receptors. Neuregulin-1 is expressed at the origin of neural crest cells.
Moreover, a tight link between neuregulin-1 expression, the migratory path, and
the target site of sympathogenic neural crest cells is observed. Sympathetic
ganglia synthesize catecholamines in the embryo and the adult. Accordingly,
catecholamine levels in mutant embryos are severely decreased, and we suggest
that the lack of catecholamines contributes to the embryonal lethality of the
erbB3 mutant mice. Thus, neuregulin-1, erbB2, and erbB3 are required for the
formation of the sympathetic nervous system; the block in development observed in
mutant mice is caused by a lack of neural crest precursor cells in the anlage of
the primary sympathetic ganglion chain. Together with previous observations,
these findings establish the neuregulin signaling system as a key regulator in
the development of neural crest cells.
PMID- 9637685
TI - Miranda as a multidomain adapter linking apically localized Inscuteable and
basally localized Staufen and Prospero during asymmetric cell division in
Drosophila.
AB - Neuroblasts in the developing Drosophila CNS asymmetrically localize the cell
fate determinants Numb and Prospero as well as prospero RNA to the basal cortex
during mitosis. The localization of Prospero requires the function of inscuteable
and miranda, whereas prospero RNA localization requires inscuteable and staufen
function. We demonstrate that Miranda contains multiple functional domains: an
amino-terminal asymmetric localization domain, which interacts with Inscuteable,
a central Numb interaction domain, and a more carboxy-terminal Prospero
interaction domain. We also show that Miranda and Staufen have similar
subcellular localization patterns and interact in vitro. Furthermore, miranda
function is required for the asymmetric localization of Staufen. Miranda
localization is disrupted by the microfilament disrupting agent latrunculin A.
Our results suggest that Miranda directs the basal cortical localization of
multiple molecules, including Staufen and prospero RNA, in mitotic neuroblasts in
an actin-dependent manner.
PMID- 9637686
TI - Miranda mediates asymmetric protein and RNA localization in the developing
nervous system.
AB - Neuroblasts undergo asymmetric stem cell divisions to generate a series of
ganglion mother cells (GMCs). During these divisions, the cell fate determinant
Prospero is asymmetrically partitioned to the GMC by Miranda protein, which
tethers it to the basal cortex of the dividing neuroblast. Interestingly,
prospero mRNA is similarly segregated by the dsRNA binding protein, Staufen. Here
we show that Staufen interacts in vivo with a segment of the prospero 3' UTR.
Staufen protein and prospero RNA colocalize to the apical side of the neuroblast
at interphase, but move to the basal side during prophase. Both the apical and
basal localization of Staufen are abolished by the removal of a conserved domain
from the carboxyl terminus of the protein, which interacts in a yeast two-hybrid
screen with Miranda protein. Furthermore, Miranda colocalizes with Staufen
protein and prospero mRNA during neuroblast divisions, and neither Staufen nor
prospero RNA are localized in miranda mutants. Thus Miranda, which localizes
Prospero protein, also localizes prospero RNA through its interaction with
Staufen protein.
PMID- 9637687
TI - Binary sibling neuronal cell fate decisions in the Drosophila embryonic central
nervous system are nonstochastic and require inscuteable-mediated asymmetry of
ganglion mother cells.
AB - Asymmetric cell division is a widespread mechanism in developing tissues that
leads to the generation of cell diversity. In the embryonic central nervous
system of Drosophila melanogaster, secondary precursor cells-ganglion mother
cells (GMCs)-divide and produce postmitotic neurons that take on different cell
fates. In this study, we show that binary fate decision of two pairs of sibling
neurons is accomplished through the interplay of Notch (N) signaling and the
intrinsic fate determinant Numb. We show that GMCs have apical-basal polarity and
Numb localization and the orientation of division are coordinated to segregate
Numb to only one sibling cell. The correct positioning of Numb and the proper
orientation of division require Inscuteable (Insc). Loss of insc results in the
generation of equivalent sibling cells. Our results provide evidence that sibling
neuron fate decision is nonstochastic and normally depends on the presence of
Numb in one of the two siblings. Moreover, our data suggest that the fate of some
sibling neurons may be regulated by signals that do not require lateral
interaction between the sibling cells.
PMID- 9637688
TI - The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary
complex with the anaphase-promoting complex to control anaphase initiation.
AB - The spindle assembly checkpoint mechanism delays anaphase initiation until all
chromosomes are aligned at the metaphase plate. Activation of the anaphase
promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from
mitosis, and APC has been implicated as a target for the checkpoint intervention.
We show that the human checkpoint protein hMAD2 prevents activation of APC by
forming a hMAD2-CDC20-APC complex. When injected into Xenopus embryos, hMAD2
arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein
exists in two-folded states: a tetramer and a monomer. Both the tetramer and the
monomer bind to CDC20, but only the tetramer inhibits activation of APC and
blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for
inhibition, and a change in hMAD2 structure may play a role in transducing the
checkpoint signal. There are at least three different forms of mitotic APC that
can be detected in vivo: an inactive hMAD2-CDC20-APC ternary complex present at
metaphase, a CDC20-APC binary complex active in degrading specific substrates at
anaphase, and a CDH1-APC complex active later in mitosis and in G1. We conclude
that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an
upstream signal to inhibit activation of APC.
PMID- 9637689
TI - A bacterial ATP-dependent, enhancer binding protein that activates the
housekeeping RNA polymerase.
AB - A commonly accepted view of gene regulation in bacteria that has emerged over the
last decade is that promoters are transcriptionally activated by one of two
general mechanisms. The major type involves activator proteins that bind to DNA
adjacent to where the RNA polymerase (RNAP) holoenzyme binds, usually assisting
in recruitment of the RNAP to the promoter. This holoenzyme uses the housekeeping
sigma70 or a related factor, which directs the core RNAP to the promoter and
assists in melting the DNA near the RNA start site. A second type of mechanism
involves the alternative sigma factor (called sigma54 or sigmaN) that directs
RNAP to highly conserved promoters. In these cases, an activator protein with an
ATPase function oligomerizes at tandem sites far upstream from the promoter. The
nitrogen regulatory protein (NtrC) from enteric bacteria has been the model for
this family of activators. Activation of the RNAP/sigma54 holoenzyme to form the
open complex is mediated by the activator, which is tethered upstream. Hence,
this class of protein is sometimes called the enhancer binding protein family or
the NtrC class. We describe here a third system that has properties of each of
these two types. The NtrC enhancer binding protein from the photosynthetic
bacterium, Rhodobacter capsulatus, is shown in vitro to activate the housekeeping
RNAP/sigma70 holoenzyme. Transcriptional activation by this NtrC requires ATP
binding but not hydrolysis. Oligomerization at distant tandem binding sites on a
supercoiled template is also necessary. Mechanistic and evolutionary questions of
these systems are discussed.
PMID- 9637690
TI - Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding
heparan sulfate 2-sulfotransferase.
AB - Heparan sulfate proteoglycans have been implicated in the presentation of a
number of secreted signaling molecules to their signal-transducing receptors. We
have characterized a gene trap mutation in the gene encoding a heparan sulfate
biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice
were generated from embryonic stem cells harboring this insertion. lacZ reporter
gene activity in heterozygous embryos demonstrates that the gene is expressed
differentially during embryogenesis, presumably directing dynamic changes in
heparan sulfate structure. Moreover, mice homozygous for the Hs2st gene trap
allele die in the neonatal period, exhibiting bilateral renal agenesis and
defects of the eye and the skeleton. Analysis of kidney development in Hs2st
mutants reveals that the gene is not required for two early events-ureteric bud
outgrowth from the Wolffian duct and initial induction of Pax-2 expression in the
metanephric mesenchyme. It is required, however, for mesenchymal condensation
around the ureteric bud and initiation of branching morphogenesis. Because 2-O
sulfation has been shown to influence the functional interactions of ligands with
heparan sulfate in vitro, we discuss the possibility that the Hs2st mutant
phenotype is a consequence of compromised interactions between growth factors and
their signal-transducing receptors. These data provide the first genetic evidence
that the regulated synthesis of differentially glycosylated proteoglycans can
affect morphogenesis during vertebrate development.
PMID- 9637691
TI - The C/EBPbeta transcription factor regulates epithelial cell proliferation and
differentiation in the mammary gland.
AB - Studies of C/EBPbeta-deficient mice have demonstrated a pivotal role for this
transcription factor in hematopoiesis, adipogenesis, and ovarian function. Here
we show that C/EBPbeta is also essential for normal development and function of
the mammary gland. Ductal morphogenesis in virgin C/EBPbeta-deficient mice was
disrupted, with ducts displaying reduced growth and branching. To distinguish
whether the effect of C/EBPbeta deficiency on mammary epithelium is indirect or
cell autonomous, we performed ovarian and mammary gland transplants. Transplants
of wild-type ovaries into mutant females partially restored ductal morphogenesis
during puberty but failed to support mammopoiesis during pregnancy. At term,
mutant mice harboring wild-type ovaries exhibited reduced alveolar proliferation
and impaired epithelial cell differentiation, including a complete absence of
milk protein expression. Mammary gland transplant experiments demonstrated that
development of C/EBPbeta-deficient epithelium was defective within a wild-type
stroma and host background. Cell proliferation during pregnancy was reduced and
differentiation, as measured by the activity of milk protein genes, was
inhibited. However, wild-type epithelium developed in a C/EBPbeta-deficient
stroma. Thus, C/EBPbeta plays an essential, cell autonomous role in the
proliferation and differentiation of mammary secretory epithelial cells and is
required for the activation of milk protein genes.
PMID- 9637693
TI - An ongoing debate over phenylalanine hydroxylase deficiency in phenylketonuria.
PMID- 9637692
TI - C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis,
lobuloalveolar proliferation, and functional differentiation in the mouse mammary
gland.
AB - The CCAAT/enhancer binding proteins (C/EBPs) are differentially expressed
throughout mammary gland development and interact with binding sites within the
promoter of a milk protein gene, beta-casein. The specific roles of C/EBPbeta and
C/EBPalpha in mouse mammary gland development and differentiation have been
investigated in mice that carry targeted deletions of these genes. C/EBPbeta-/-
virgin mice exhibited cystic, enlarged mammary ducts with decreased secondary
branching. Transplantation of C/EBPbeta-/- mammary epithelium into the cleared
mammary fat pads of nude mice confirmed that this defect in ductal morphogenesis
was intrinsic to the epithelium. When treated with estrogen/progesterone (E+P) to
simulate pregnancy, C/EBPbeta-/- mammary glands displayed only limited
lobuloalveolar development and ductal side branching. Primary mammary epithelial
cells obtained from E+P-treated C/EBPbeta-/- mice that were cultured on
extracellular matrix gels did not functionally differentiate in response to
lactogenic hormones despite their organization into three-dimensional structures.
Expression of beta-casein protein was inhibited 85%-100% and whey acidic protein
(WAP) was undetectable. In contrast, no detectable alterations in mammary
development or beta-casein expression were observed in mammary outgrowths derived
from newborn C/EBPalpha-/- mammary epithelium transplanted into the cleared
mammary fat pads of syngeneic hosts. These results demonstrate that C/EBPbeta,
but not C/EBPalpha, is required for ductal morphogenesis, lobuloalveolar
development, and functional differentiation of mammary epithelial cells.
PMID- 9637694
TI - Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease
in a streptococcal cell wall-induced arthritis model.
AB - Transforming growth factor beta is a potent immunomodulator with both pro- and
antiinflammatory activities. Based on its immunosuppressive actions, exogenous
TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases.
To further explore the potential therapeutic role of TGF-beta, we administered a
plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal
cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF
beta1, but not vector DNA, administered at the peak of the acute phase profoundly
suppressed the subsequent evolution of chronic erosive disease typified by
disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/
0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as
the chronic phase commenced virtually eliminated subsequent inflammation and
arthritis. Both radiologic and histopathologic as well as molecular evidence
supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology,
with decreases in the inflammatory cell infiltration, pannus formation, cartilage
and bone destruction, and the expression of proinflammatory cytokines that
characterize this model. Increases in TGF-beta1 protein were detected in the
circulation of TGF-beta1 DNA-treated animals, consistent with the observed
therapeutic effects being TGF-beta1 dependent. These observations provide the
first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a
mechanism to deliver this potent cytokine that effectively suppresses ongoing
inflammatory pathology in arthritis.
PMID- 9637695
TI - Androgens stimulate early stages of follicular growth in the primate ovary.
AB - The concept that androgens are atretogenic, derived from murine ovary studies, is
difficult to reconcile with the fact that hyperandrogenic women have more
developing follicles than normal-cycling women. To evaluate androgen's effects on
primate follicular growth and survival, normal-cycling rhesus monkeys were
treated with placebo-, testosterone-(T), or dihydrotestosterone-sustained release
implants, and ovaries were taken for histological analysis after 3-10 d of
treatment. Growing preantral and small antral follicles up to 1 mm in diameter
were significantly and progressively increased in number and thecal layer
thickness in T-treated monkeys from 3-10 d. Granulosa and thecal cell
proliferation, as determined by immunodetection of the Ki67 antigen, were
significantly increased in these follicles. Preovulatory follicles (> 1 mm),
however, were not increased in number in androgen-treated animals. Follicular
atresia was not increased and there were actually significantly fewer apoptotic
granulosa cells in the T-treated groups. Dihydrotestosterone treatment had
identical effects, indicating that these growth-promoting actions are mediated by
the androgen receptor. These findings show that, over the short term at least,
androgens are not atretogenic and actually enhance follicular growth and survival
in the primate. These new data provide a plausible explanation for the
pathogenesis of "polycystic" ovaries in hyperandrogenism.
PMID- 9637696
TI - Functional significance of cardiac myosin essential light chain isoform switching
in transgenic mice.
AB - The different functions of the ventricular- and atrial-specific essential myosin
light chains are unknown. Using transgenesis, cardiac-specific overexpression of
proteins can be accomplished. The transgenic paradigm is more useful than
originally expected, in that the mammalian heart rigorously controls sarcomeric
protein stoichiometries. In a clinical subpopulation suffering from heart disease
caused by congenital malformations of the outflow tract, an ELC1v-->ELC1a isoform
shift correlated with increases in cross-bridge cycling kinetics as measured in
skinned fibers derived from the diseased muscle. We have used transgenesis to
replace the ventricular isoform of the essential myosin light chain with the
atrial isoform. The ELC1v--> ELC1a shift in the ventricle resulted in similar
functional alterations. Unloaded velocities as measured by the ability of the
myosin to translocate actin filaments in the in vitro motility assay were
significantly increased as a result of the isoform substitution. Unloaded
shortening velocity was also increased in skinned muscle fibers, and at the whole
organ level, both contractility and relaxation were significantly increased. This
increase in cardiac function occurred in the absence of a hypertrophic response.
Thus, ELC1a expression in the ventricle appears to be advantageous to the heart,
resulting in increased cardiac function.
PMID- 9637697
TI - Vaccination with a recombinant fragment of collagen adhesin provides protection
against Staphylococcus aureus-mediated septic death.
AB - Staphylococcus aureus is a major cause of nosocomial and community-acquired
infections. Morbidity and mortality due to infections such as sepsis,
osteomyelitis, septic arthritis, and invasive endocarditis remain high despite
the use of antibiotics. The emergence of antibiotic resistant super bugs mandates
that alternative strategies for the prevention and treatment of S. aureus
infections are developed. We investigated the ability of vaccination with a
recombinant fragment of the S. aureus collagen adhesin to protect mice against
sepsis-induced death. Actively immunized NMRI mice were intravenously inoculated
with the S. aureus clinical isolate strain Phillips. 14 d after inoculation,
mortality in the collagen adhesin-vaccinated group was only 13%, compared with
87% in the control antigen immunized group (P < 0.001). To determine if the
protective effect was antibody mediated, we passively immunized naive mice with
collagen adhesin-specific antibodies. Similar to the active immunization
strategy, passive transfer of collagen adhesin-specific antibodies protected mice
against sepsis-induced death. In vitro experiments indicated that S. aureus
opsonized with sera from collagen adhesin immunized mice promoted phagocytic
uptake and enhanced intracellular killing compared with bacteria opsonized with
sera from control animals. These results indicate that the collagen adhesin is a
viable target in the development of immunotherapeutics against S. aureus.
PMID- 9637698
TI - Regulation of proliferation of human colonic subepithelial myofibroblasts by
mediators important in intestinal inflammation.
AB - An increase in myofibroblast number may be necessary for wound healing but may
also lead to postinflammatory scarring. We have, therefore, studied the role of
mediators important in inflammatory bowel disease in regulating proliferation of
human colonic myofibroblasts. Using primary cultures of these cells, we have
shown increases in [3H]thymidine incorporation in response to platelet-derived
growth factor (EC50 = 14 ng/ml), basic fibroblast growth factor (EC50 = 2.2
ng/ml), and epidermal growth factor (EC50 = 1.1 ng/ml). Coulter counting of cell
suspensions demonstrated increases in cell number with these growth factors along
with insulin-like growth factor-I and -II. In addition the proinflammatory
cytokines IL-1beta and TNF-alpha produced increases in [3H]thymidine
incorporation. IL-1beta and platelet-derived growth factor together produced an
increase in [3H]thymidine greater than either agonist alone; this effect was not,
however, seen when we examined changes in cell numbers. Finally, we demonstrate a
mechanism whereby these responses may be downregulated: vasoactive intestinal
peptide (1 microM) elevates cyclic AwMP in these cells 4. 2-fold over control and
produces a dose-related inhibition of platelet-derived growth factor-driven
proliferation with a maximum inhibition of 33% at 1 microM.
PMID- 9637699
TI - Identification of the principal proteoglycan-binding site in LDL. A single-point
mutation in apo-B100 severely affects proteoglycan interaction without affecting
LDL receptor binding.
AB - The subendothelial retention of LDLs through their interaction with proteoglycans
has been proposed to be a key process in the pathogenesis of atherosclerosis. In
vitro studies have identified eight clusters of basic amino acids in delipidated
apo-B100, the protein moiety of LDL, that bind the negatively charged
proteoglycans. To determine which of these sites is functional on the surface of
LDL particles, we analyzed the proteoglycan-binding activity of recombinant human
LDL isolated from transgenic mice. Substitution of neutral amino acids for the
basic amino acids residues in site B (residues 3359-3369) abolished both the
receptor-binding and the proteoglycan-binding activities of the recombinant LDL.
Chemical modification of the remaining basic residues caused only a marginal
further reduction in proteoglycan binding, indicating that site B is the primary
proteoglycan-binding site of LDL. Although site B was essential for normal
receptor-binding and proteoglycan-binding activities, these activities could be
separated in recombinant LDL containing single-point mutation. Recombinant LDL
with a K3363E mutation, in which a glutamic acid had been inserted into the basic
cluster RKR in site B, had normal receptor binding but interacted defectively
with proteoglycans; in contrast, another mutant LDL, R3500Q, displayed defective
receptor binding but interacted normally with proteoglycans. LDL with normal
receptor-binding activity but with severely impaired proteoglycan binding will be
a unique resource for analyzing the importance of LDL- proteoglycan interaction
in atherogenesis. If the subendothelial retention of LDL by proteoglycans is the
initial event in early atherosclerosis, then LDL with defective proteoglycan
binding may have little or no atherogenic potential.
PMID- 9637700
TI - Stimulation of bile duct epithelial secretion by glybenclamide in normal and
cholestatic rat liver.
AB - Cholestasis is a cardinal complication of liver disease, but most treatments are
merely supportive. Here we report that the sulfonylurea glybenclamide potently
stimulates bile flow and bicarbonate excretion in the isolated perfused rat
liver. Video-microscopic studies of isolated hepatocyte couplets and isolated
bile duct segments show that this stimulatory effect occurs at the level of the
bile duct epithelium, rather than through hepatocytes. Measurements of cAMP,
cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide
directly activates Na+-K+-2Cl- cotransport, rather than other transporters or
conventional second-messenger systems that link to secretory pathways in these
cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced
cholestasis show that glybenclamide retains its stimulatory effects on bile flow
and bicarbonate excretion even under these conditions. These findings suggest
that bile duct epithelia may represent an important new therapeutic target for
treatment of cholestatic disorders.
PMID- 9637701
TI - Gender differences in ethanol preference and ingestion in rats. The role of the
gonadal steroid environment.
AB - An ethanol oral self administration paradigm showed the existence of gender
differences in alcohol preference in rats: whereas males and females initiated
alcohol drinking at similar rates, females maintained their preference for
ethanol over a longer duration. Neonatal estrogenization of females, which
effectively confers a male phenotype on a genetically female brain, resulted in
patterns of drinking that were similar to those displayed by intact male rats,
indicating that gender differences in alcohol drinking patterns may be, at least
partially, accounted for by sexual differentiation of the brain. To test whether
gonadal steroids also exert activational effects on ethanol-seeking behavior, we
also examined the effects of gonadectomy alone, or in combination with gonadal
steroid replacement therapy. Castration did not significantly alter ethanol
consumption in males, although treatment of castrated rats with
dihydrotestosterone resulted in a significant inhibition of this parameter. As
compared with the situation in intact female rats, ethanol ingestion was
significantly reduced in ovariectomized female rats receiving estradiol (E2) and
in ovariectomized female rats receiving combined E2 and progesterone replacement
therapy. However, neither ovariectomy nor progesterone replacement in
ovariectomized rats resulted in ethanol drinking patterns that were different
compared to those observed in intact female controls. Thus, dihydrotestosterone
and E2, respectively, appear to exert modulatory influences on the male and
female rats' preference for ethanol, but further investigations are necessary to
determine to what extent these effects result from activational actions on the
brain.
PMID- 9637702
TI - In vitro generation of human cytomegalovirus pp65 antigenemia, viremia, and
leukoDNAemia.
AB - Immunocompromised patients with disseminated human cytomegalovirus (HCMV)
infection have circulating PMN carrying HCMV pp65 (antigenemia), infectious virus
(viremia), and viral DNA (leukoDNAemia). Because HCMV does not fully replicate in
PMN, it is generally hypothesized that virions and viral materials are taken up
by phagocytosis from fully permissive HCMV-infected endothelial cells. However,
no experimental evidence has ever been provided for these PMN-endothelium
interactions. PMN from 11 donors were cocultured with endothelial cells infected
with an endothelium-adapted HCMV strain and with human fibroblasts infected with
low-passaged clinical and laboratory-adapted HCMV strains. pp65-positive PMN were
detected after coculture with both HCMV-infected endothelial and fibroblast
cells, provided that wild and not laboratory-adapted strains were used. In
addition, cocultured PMN carried infectious virus as demonstrated by virus
isolation and presence of complete virus particles by electron microscopy.
Moreover, high levels of viral DNA were consistently detected by quantitative PCR
in cocultured PMN. Thus, we have generated in vitro the three most important
viral parameters detected in patients with disseminated HCMV infection
(antigenemia, viremia, and leukoDNAemia). The failure of laboratory-adapted HCMV
strain to induce this phenomenon demonstrates that important modifications have
occurred in attenuated viral strains affecting basic biological functions.
PMID- 9637703
TI - Inhibition of intracellular degradation increases secretion of a mutant form of
alpha1-antitrypsin associated with profound deficiency.
AB - The mutant Z form of alpha1-antitrypsin (alpha1AT) is responsible for > 95% of
all individuals with alpha1AT deficiency, an important inherited cause of
emphysema and liver disease. Since secreted Z alpha1AT is a functional
antiprotease, we hypothesized that interrupting catabolism of retained Z alpha1AT
might increase its transport out of cells, causing an increase in extracellular
protease protection. Both the protein translation inhibitor cycloheximide and the
specific inhibitor of proteasome function, lactacystin, prevented intracellular
degradation of Z alpha1AT. Moreover, this inhibition of degradation was
associated with partial restoration of Z alpha1AT vesicular transport. This
effect was observed in a model system of transfected CHO cells as well as in
human alveolar macrophages synthesizing Z alpha1AT. This study supports the
hypothesis that altering the intracellular fate of a mutant protein may be an
option in the treatment of diseases associated with misfolded but potentially
functional proteins.
PMID- 9637704
TI - Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-
deficient mice.
AB - Previous studies of osteopetrotic (op) mice lacking macrophage colony-stimulating
factor (M-CSF) have revealed an inhibition of atherosclerosis development in the
apolipoprotein E (apo E)-deficient model and in a diet-induced model. Using LDL
receptor-deficient mice, we now show that atheroma development depends on M-CSF
concentration, as not only did homozygous osteopetrotic (op/op) mice have
dramatically reduced lesions (approximately 0.3% of control lesion size) but
heterozygous (op/+) mice had lesions < 1% of controls. Mice heterozygous for the
op mutation (op/+) had plasma levels of M-CSF about half those in controls (+/+).
The finding that an approximately 2-fold reduction in M-CSF expression reduced
lesion size approximately 100-fold suggests the requirement for a threshold level
of M-CSF. The effect of M-CSF on atherosclerosis did not appear to be mediated
either by changes in plasma lipoprotein levels or alterations in the number of
circulating monocytes, since both op/op and op/+ mice exhibited higher levels of
atherogenic lipoprotein particles and (op/+) mice showed a near normal number of
circulating monocytes. LDL receptor-null littermates of genotypes from op/op,
op/+, to +/+ showed monocyte differentials of approximately 4.5, 8, and 10%,
respectively. Taken together, these results suggest that the effects of M-CSF on
atherogenesis may not be mediated by expression of M-CSF systemically or by
modulation of the number of circulating monocytes. These studies support the
conclusion that M-CSF participates critically in fatty streak formation and
progression to a complex fibrous lesion.
PMID- 9637705
TI - Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin
and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide
synthase in vascular endothelial cells.
AB - Endothelial dysfunction associated with atherosclerosis has been attributed to
alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or to an excess of
endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase
inhibitors (statins) have been shown to ameliorate endothelial function. However,
the physiological basis of this observation is largely unknown. We investigated
the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression
and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and
protein levels in bovine aortic endothelial cells. These agents inhibited pre
proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70%
maximum inhibition) and reduced immunoreactive ET-1 levels (25-50%). This
inhibitory effect was maintained in the presence of oxidized LDL (1-50
microg/ml). No significant modification of pre-proET-1 mRNA half-life was
observed. In addition, mevalonate, but not cholesterol, reversed the statin
mediated decrease of pre-proET-1 mRNA levels. eNOS mRNA expression was reduced by
oxidized LDL in a dose-dependent fashion (up to 57% inhibition), whereas native
LDL had no effect. Statins were able to prevent the inhibitory action exerted by
oxidized LDL on eNOS mRNA and protein levels. Hence, these drugs might influence
vascular tone by modulating the expression of endothelial vasoactive factors.
PMID- 9637706
TI - beta2-Microglobulin mutations, HLA class I antigen loss, and tumor progression in
melanoma.
AB - The potential negative impact of HLA class I antigen abnormalities on the outcome
of T cell-based immunotherapy of melanoma has prompted us to investigate the
mechanisms underlying lack of HLA class I antigen expression by melanoma cell
lines Me18105, Me9923, and Me1386. Distinct mutations in the beta2-microglobulin
(beta2m) gene were identified in each cell line which result in loss of
functional beta2m. In Me18105 cells, an aberrant splicing mechanism caused by an
A--> G point mutation in the splice acceptor site of intron 1 of the beta2m gene,
deletes 11 bp from the beta2m mRNA creating a shift in the reading frame. In
Me9923 cells a 14-bp deletion in exon 2 and in Me1386 cells a CT deletion in exon
1 of the beta2m gene produce a frameshift mutation. The beta2m gene mutations
identified in Me18105, Me9923, and Me1386 cells were also detected in the
surgically removed melanoma lesions from which the cell lines originated.
Transfection of each melanoma cell line with a wild-type beta2m gene restored HLA
class I antigen expression and, in Me18105 cells, recognition by Melan-A/MART-1
specific, HLA-A2-restricted cytotoxic T lymphocytes. Interestingly, the beta2m
mutation present in Me9923 cells that were derived from a metastatic lesion was
also found in the Me9923P cell line that originated from the autologous primary
lesion. These data suggest that beta2m mutations in melanoma cells may be an
early event in progression to the malignant phenotype.
PMID- 9637707
TI - Time-dependent changes in the density and hemoglobin F content of biotin-labeled
sickle cells.
AB - Sickle red blood cells (RBC) are subject to a number of important cellular
changes and selection pressures. In this study, we validated a biotin RBC label
by comparison to the standard 51Cr label, and used it to study changes that occur
in sickle cells as they age. Sickle RBC had a much shorter lifespan than normal
RBC, but the two labels gave equivalent results for each cell type. A variable
number of sickle, but not normal, RBC disappeared from the circulation during the
first few hours after reinfusion. The number of biotinylated sickle reticulocytes
was decreased by 50% after 24 h and 75% after 48 h, with a gradual decrease in
the amount of reticulum per cell. The labeled sickle cells exhibited major
density increases during the first 4-6 d after reinfusion, with smaller changes
thereafter. A small population of very light, labeled sickle RBC was essentially
constant in number after the first few days. Fetal hemoglobin (HbF) content was
determined in isolated biotinylated sickle RBC after reinfusion, allowing an
estimate of lifespan for RBC containing HbF (F cells) and non-F cells. The
lifespan of sickle biotinylated RBC lacking HbF was estimated to be approximately
2 wk, whereas F cells survived 6-8 wk.
PMID- 9637708
TI - Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the
epithelial sodium channel in the Xenopus oocyte expression system.
AB - Liddle syndrome is an autosomal dominant form of hypertension resulting from
deletion or missense mutations of a PPPxY motif in the cytoplasmic COOH terminus
of either the beta or gamma subunit of the epithelial Na channel (ENaC). These
mutations lead to increased channel activity. In this study we show that wild
type ENaC is downregulated by intracellular Na+, and that Liddle mutants decrease
the channel sensitivity to inhibition by intracellular Na+. This event results at
high intracellular Na+ activity in 1.2-2.4-fold higher cell surface expression,
and 2.8-3.5-fold higher average current per channel in Liddle mutants compared
with the wild type. In addition, we show that a rapid increase in the
intracellular Na+ activity induced downregulation of the activity of wild-type
ENaC, but not Liddle mutants, on a time scale of minutes, which was directly
correlated to the magnitude of the Na+ influx into the oocytes. Feedback
inhibition of ENaC by intracellular Na+ likely represents an important cellular
mechanism for controlling Na+ reabsorption in the distal nephron that has
important implications for the pathogenesis of hypertension.
PMID- 9637709
TI - Association and direct activation of signal transducer and activator of
transcription1alpha by platelet-derived growth factor receptor.
AB - PDGF stimulates tyrosine phosphorylation of Janus kinase 1 (JAK1) and the signal
transducer and activator of transcription 1 (STAT1alpha). However, it is not
known whether JAKs are required for STAT1alpha phosphorylation or if the PDGF
receptor itself can directly tyrosine phosphorylate and activate STAT1alpha. In
vitro immunecomplex kinase assay of PDGF beta receptor (PDGFR) or STAT1alpha
immunoprecipitates from lysates of mesangial cells treated with PDGF showed
phosphorylation of a 91- and an 185-kD protein. Incubation of lysates prepared
from quiescent mesangial cells with purified PDGFR resulted in STAT1alpha
activation. Immunodepletion of Janus kinases from the cell lysate before
incubation with the purified PDGFR showed no effect on STAT1alpha activation.
Moreover, lysates from mesangial cells treated with JAK2 inhibitor, retained
significant STAT1alpha activity. To confirm that STAT1alpha is a substrate for
PDGFR, STAT1alpha protein was prepared by in vitro transcription and translation.
The addition of purified PDGFR to the translated STAT1alpha resulted in its
phosphorylation. This in vitro phosphorylated and activated protein also forms a
specific protein-DNA complex. Dimerization of the translated STAT1alpha protein
was also required for its DNA binding. Incubation of pure STAT1alpha with
autophosphorylated PDGFR resulted in physical association of the two proteins.
These data indicate that activated PDGFR may be sufficient to tyrosine
phosphorylate and thus directly activate STAT1alpha.
PMID- 9637710
TI - Delta-aminolevulinic acid transport by intestinal and renal peptide transporters
and its physiological and clinical implications.
AB - Delta-aminolevulinic acid (ALA) is the precursor of porphyrin synthesis and has
been recently used in vitro and in clinical studies as an endogenous
photosensitizer for photodynamic therapy in the treatment of various tumors. For
this purpose, ALA is given topically, systemically, or orally. When administered
by the oral route, it shows excellent intestinal absorption. ALA is also
efficiently reabsorbed in the renal proximal tubule after glomerular filtration.
However, the pathways and mechanisms for its transmembrane transport into
epithelial cells of intestine and kidney are unknown. Here we demonstrate that
ALA uses the intestinal and renal apical peptide transporters for entering into
epithelial cells. Kinetics and characteristics of ALA transport were determined
in Xenopus laevis ooyctes and Pichia pastoris yeast cells expressing either the
cloned intestinal peptide transporter PEPT1 or the renal form PEPT2. By using
radiolabeled ALA and electrophysiological techniques in these heterologous
expression systems, we established that: (a) PEPT1 and PEPT2 translocate 3H-ALA
by saturable and pH-dependent transport mechanisms, (b) that ALA and di
/tripeptides, but not GABA or related amino acids, compete at the same substrate
binding site of the carriers, and (c) that ALA transport is electrogenic in
nature as a consequence of H+/ALA cotransport. Reverse transcriptase-PCR analysis
performed with specific primers for PEPT1 and PEPT2 in rabbit tissues
demonstrates that, in particular, the PEPT2 mRNA is expressed in a variety of
other tissues including lung, brain, and mammary gland, which have been shown to
accumulate ALA. This suggests that these tissues could take up the porphyrin
precusor via expressed peptide transporters, providing the endogenous
photosensitizers for efficient photodynamic therapy.
PMID- 9637711
TI - Hypertonicity regulates the function of human neutrophils by modulating
chemoattractant receptor signaling and activating mitogen-activated protein
kinase p38.
AB - Excessive neutrophil activation causes posttraumatic complications, which may be
reduced with hypertonic saline (HS) resuscitation. We tested if this is because
of modulated neutrophil function by HS. Clinically relevant hypertonicity (10-25
mM) suppressed degranulation and superoxide formation in response to fMLP and
blocked the activation of the mitogen activated protein kinases (MAPK) ERK1/2 and
p38, but did not affect Ca2+ mobilization. HS did not suppress oxidative burst in
response to phorbol myristate acetate (PMA). This indicates that HS suppresses
neutrophil function by intercepting signal pathways upstream of or apart from
PKC. HS activated p38 by itself and enhanced degranulation in response to PKC
activation. This enhancement was reduced by inhibition of p38 with SB203580,
suggesting that p38 up-regulation participates in HS-induced enhancements of
degranulation. HS had similar effects on the degranulation of cells that were
previously stimulated with fMLP, but had no effect on its own, suggesting that HS
enhancement of degranulation requires another signal. We conclude that depending
on other stimuli, HS can suppress neutrophil activation by intercepting multiple
receptor signals or augment degranulation by enhancing p38 signaling. In patients
HS resuscitation may reduce posttraumatic complications by preventing neutrophil
activation via chemotactic factors released during reperfusion.
PMID- 9637712
TI - Nitric oxide inhibition induces early activation of type I collagen gene in renal
resistance vessels and glomeruli in transgenic mice. Role of endothelin.
AB - Hypertension is often associated with the development of nephroangio- and
glomerulo-sclerosis. This pathophysiological process is due to increased
extracellular matrix protein, particularly type I collagen, accumulation. This
study investigated whether nitric oxide (NO) synthesis is involved in the
mechanism(s) regulating activation of the collagen I gene in afferent arterioles
and glomeruli. Experiments were performed on transgenic mice harboring the
luciferase gene under the control of the collagen I-alpha2 chain promoter
[procolalpha2(I)]. Measurements of luciferase activity provide highly sensitive
estimates of collagen I gene activation. NO synthesis was inhibited by NG-nitro-L
arginine methyl ester (L-NAME) (20 mg/kg per day) for a period of up to 14 wk.
Systolic blood pressure was increased after 6 wk of treatment (117+/-2 versus
129+/-2 mmHg, P < 0.01) and reached a plateau after 10 wk (around 160 mmHg).
Luciferase activity was increased in freshly isolated afferent arterioles and
glomeruli as early as week 4 of L-NAME treatment (150 and 200% of baseline, P <
0.01, respectively). The activation of procolalpha2(I) became more pronounced
with time, and at 14 wk increased four- and tenfold compared with controls in
afferent arterioles and glomeruli, respectively (P < 0.001). In contrast,
luciferase activity remained unchanged in aorta and heart up to 8 wk and was
increased thereafter. Increased histochemical staining for extracellular matrix
deposition, and particularly of collagen I, was detected in afferent arterioles
and glomeruli after 10 wk of L-NAME treatment. This fibrogenic process was
accompanied by an increased urinary excretion rate of endothelin. In separate
experiments, the stimulatory effect of L-NAME on collagen I gene activation was
abolished when animals were treated with bosentan, an endothelin receptor
antagonist. Similarly, bosentan reduced the increased extracellular matrix
deposition in afferent arterioles and glomeruli during NO inhibition.
Interestingly, bosentan had no effect on the L-NAME- induced increase of systolic
pressure. These data indicate that NO inhibition induces an early activation of
the collagen I gene in afferent arterioles and glomeruli. This activation in the
kidney precedes the increase in blood pressure and the procolalpha2(I) activation
in heart and aorta, suggesting a specific renal effect of NO blockade on collagen
I gene expression that is independent of increased blood pressure and, at least
partly, mediated through stimulation of the endothelin receptor. Use of
procolalpha2(I) transgenic mice provides a novel and efficient model to study the
pathophysiological mechanism(s) regulating renal fibrosis.
PMID- 9637713
TI - A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating
mitochondrial membrane perturbation.
AB - The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the
membrane-damaging effects associated with hydrophobic bile acids. This study was
undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid
(DCA), as well as from ethanol, TGF-beta1, Fas ligand, and okadaic acid; and to
(b) determine whether mitochondrial membrane perturbation is modulated by UDCA.
DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes
determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling
assay and nuclear staining, respectively (P < 0.001). Apoptosis in isolated rat
hepatocytes increased 12-fold after incubation with 0.5% ethanol (P < 0.001). HuH
7 cells exhibited increased apoptosis with 1 nM TGF-beta1 (P < 0. 001) or DCA at
>/= 100 microM (P < 0.001), as did Hep G2 cells after incubation with anti-Fas
antibody (P < 0.001). Finally, incubation with okadaic acid induced significant
apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with
each of the apoptosis-inducing agents was associated with a 50-100% inhibition of
apoptotic changes (P < 0.001) in all the cell types. Also, UDCA reduced the
mitochondrial membrane permeability transition (MPT) in isolated mitochondria
associated with both DCA and phenylarsine oxide by > 40 and 50%, respectively (P
< 0.001). FACS(R) analysis revealed that the apoptosis-inducing agents decreased
the mitochondrial transmembrane potential and increased reactive oxygen species
production (P < 0.05). Coadministration of UDCA was associated with significant
prevention of mitochondrial membrane alterations in all cell types. The results
suggest that UDCA plays a central role in modulating the apoptotic threshold in
both hepatocytes and nonliver cells, and inhibition of MPT is at least one
pathway by which UDCA protects against apoptosis.
PMID- 9637714
TI - A truncated cardiac troponin T molecule in transgenic mice suggests multiple
cellular mechanisms for familial hypertrophic cardiomyopathy.
AB - Mutations in multiple cardiac sarcomeric proteins including myosin heavy chain
(MyHC) and cardiac troponin T (cTnT) cause a dominant genetic heart disease,
familial hypertrophic cardiomyopathy (FHC). Patients with mutations in these two
genes have quite distinct clinical characteristics. Those with MyHC mutations
demonstrate more significant and uniform cardiac hypertrophy and a variable
frequency of sudden death. Patients with cTnT mutations generally exhibit mild or
no hypertrophy, but a high frequency of sudden death at an early age. To
understand the basis for these distinctions and to study the pathogenesis of the
disease, we have created transgenic mice expressing a truncated mouse cTnT allele
analogous to one found in FHC patients. Mice expressing truncated cTnT at low (<
5%) levels develop cardiomyopathy and their hearts are significantly smaller (18
27%) than wild type. These animals also exhibit significant diastolic dysfunction
and milder systolic dysfunction. Animals that express higher levels of transgene
protein die within 24 h of birth. Transgenic mouse hearts demonstrate myocellular
disarray and have a reduced number of cardiac myocytes that are smaller in size.
These studies suggest that multiple cellular mechanisms result in the human
disease, which is generally characterized by mild hypertrophy, but, also,
frequent sudden death.
PMID- 9637715
TI - Regulation of murine fetal-placental calcium metabolism by the calcium-sensing
receptor.
AB - The calcium-sensing receptor (CaSR) regulates PTH secretion to control the
extracellular calcium concentration in adults, but its role in fetal life is
unknown. We used CaSR gene knockout mice to investigate the role of the CaSR in
regulating fetal calcium metabolism. The normal calcium concentration in fetal
blood is raised above the maternal level, an increase that depends upon PTH
related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of
the CaSR caused a further increase in the fetal calcium level. This increase was
modestly blunted by concomitant disruption of the PTHrP gene and completely
reversed by disruption of the PTH/ PTHrP receptor gene. Serum levels of PTH and
1, 25-dihydroxyvitamin D were substantially increased above the normal low fetal
levels by disruption of the CaSR. The free deoxypyridinoline level was increased
in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal
bone resorption is increased. Placental calcium transfer was reduced, and renal
calcium excretion was increased, by disruption of the CaSR. These studies
indicate that the CaSR normally suppresses PTH secretion in the presence of the
normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR
causes fetal hyperparathyroidism and hypercalcemia, with additional effects on
placental calcium transfer.
PMID- 9637716
TI - Characterization of a CD38-like 78-kilodalton soluble protein released from B
cell lines derived from patients with X-linked agammaglobulinemia.
AB - Studies on murine B lymphocytes showed that Bruton's tyrosine kinase mediates
signal transduction induced via CD38, a nonlineage-restricted 45-kD ectoenzyme.
This signaling is defective in B cells from X-linked immunodeficient mice
affected with the analogue of human X-linked agammaglobulinemia (XLA). We
performed a structural and functional analysis of CD38 in XLA and other
immunodeficiencies, using EBV-immortalized B cells derived from such patients.
Membrane CD38 was not significantly different from controls in structure, epitope
density, enzymatic activity, and internalization upon binding of agonistic mAbs.
Meanwhile, an increased release of soluble CD38 from XLA cells was observed:
immunoprecipitation from XLA culture media yielded a protein of approximately 78
kD (p78), reacting also in Western blot and displaying both enzymatic activities
and a peptide map similar to membrane CD38. Soluble forms and homotypic
aggregations of CD38 were documented in different cell models and by
crystallographic analysis of the Aplysia ADP-ribosyl cyclase, the ancestor of
human CD38. p78 might represent the product of an altered turn-over of membrane
CD38, a starting point for studying its association with Bruton's tyrosine kinase
and its role in XLA and other B cell immunodeficiencies.
PMID- 9637717
TI - Therapeutic levels of human protein C in rats after retroviral vector-mediated
hepatic gene therapy.
AB - Protein C deficiency results in a thrombotic disorder that might be treated by
expressing a normal human protein C (hPC) gene in patients. An amphotropic
retroviral vector with a liver-specific promoter and the hPC cDNA was delivered
to rat hepatocytes in vivo during liver regeneration. Expression of hPC varied
from 55 to 203 ng/ml (1.3-5.0% of normal) for 2 wk after transduction. Expression
increased to an average of 900 ng/ml (22% of normal) in some rats and was
maintained at stable levels for 1 yr. All of these rats developed anti-hPC
antibodies and exhibited a prolonged hPC half-life in vivo. The hPC was
functional as determined by a chromogenic substrate assay after
immunoprecipitation. We conclude that most rats achieved hPC levels that would
prevent purpura fulminans, and that hepatic gene therapy might become a viable
treatment for patients with severe homozygous hPC deficiency. Anti-hPC antibodies
increased the hPC half-life and plasma levels in some rats, but did not interfere
with its functional activity. Thus, the development of antibodies against a
plasma protein does not necessarily abrogate its biological effect in gene
therapy experiments.
PMID- 9637718
TI - Cisplatin-induced apoptosis in rat dorsal root ganglion neurons is associated
with attempted entry into the cell cycle.
AB - Platinum compounds induce apoptosis in malignant cells and are used extensively
in the treatment of cancer. Total dose is limited by development of a sensory
neuropathy. We now demonstrate that when rats are administered cisplatin (2 mg/kg
i.p. for 5 d), primary sensory neurons in the dorsal root ganglion die by
apoptosis. This was reproduced by exposure of dorsal root ganglion neurons and
PC12 cells to cisplatin (3 microg/ml) in vitro. Apoptosis was confirmed by
electron microscopy, DNA laddering, and inhibition by the caspase inhibitor z
VAD.fmk (100 microM). Cell death in vitro was preceded by upregulation of cyclin
D1, cdk4, and increased phosphorylation of retinoblastoma protein; all are
indicators of cell cycle advancement. The level of p16(INK4a), an endogenous
inhibitor of the cyclin D1/cdk4 complex decreased. Exposure of PC12 cells and
dorsal root ganglion neurons to increased levels of nerve growth factor (100 ng/
ml) prevented both apoptosis and upregulation of the cell cycle markers. Cancer
cells without nerve growth factor receptors (gp140TrkA) were not protected by the
neurotrophin. This indicated that cisplatin may kill cancer cells and neurons by
a similar mechanism. In postmitotic neurons, this involves an attempt to re-enter
the cell cycle resulting in apoptosis which is specifically prevented by nerve
growth factor.
PMID- 9637720
TI - Right ventricular outflow tract tachycardia due to a somatic cell mutation in G
protein subunitalphai2.
AB - Idiopathic ventricular tachycardia is a generic term that describes the various
forms of ventricular arrhythmias that occur in patients without structural heart
disease and in the absence of the long QT syndrome. Many of these tachycardias
are focal in origin, localize to the right ventricular outflow tract (RVOT),
terminate in response to beta blockers, verapamil, vagal maneuvers, and
adenosine, and are thought to result from cAMP-mediated triggered activity. DNA
was prepared from biopsy samples obtained from myocardial tissue from a patient
with adenosine-insensitive idiopathic ventricular tachycardia arising from the
RVOT. Genomic sequences of the inhibitory G protein Galphai2 were determined
after amplification by PCR and subcloning. A point mutation (F200L) in the GTP
binding domain of the inhibitory G protein Galphai2 was identified in a biopsy
sample from the arrhythmogenic focus. This mutation was shown to increase
intracellular cAMP concentration and inhibit suppression of cAMP by adenosine. No
mutations were detected in Galphai2 sequences from myocardial tissue sampled from
regions remote from the origin of tachycardia, or from peripheral lymphocytes.
These findings suggest that somatic cell mutations in the cAMP-dependent signal
transduction pathway occurring during myocardial development may be responsible
for some forms of idiopathic ventricular tachycardia.
PMID- 9637719
TI - Growth factor activation of the estrogen receptor in vascular cells occurs via a
mitogen-activated protein kinase-independent pathway.
AB - The classical estrogen receptor ERalpha mediates many of the known cardiovascular
effects of estrogen and is expressed in male and female vascular cells. Estrogen
independent activation of ERalpha is known to occur in cells from reproductive
tissues, but has not been investigated previously in vascular cells. In this
study, transient transfection assays in human saphenous vein smooth muscle cells
(HSVSMC) and pulmonary vein endothelial cells (PVEC) demonstrated ERalpha
dependent activation of estrogen response element-based, and vascular endothelial
growth factor-based reporter plasmids by both estrogen-deficient FBS (ED-FBS) and
EGF. In nonvascular cells, ERalpha-mediated gene expression can be activated via
mitogen-activated protein (MAP) kinase- induced phosphorylation of serine 118 of
ERalpha. However, in vascular cells, we found that pharmacologic inhibition of
MAP kinase did not alter EGF-mediated ERalpha activation. In addition, a mutant
ER containing an alanine-for-serine substitution at position 118 was activated to
the same degree as the wild-type receptor by ED-FBS and EGF in both HSVSMC and
PVEC. Furthermore, constitutively active MAP kinase kinase (MAPKK) activated
ERalpha in Cos1 cells as expected, but MAPKK inhibited ER activation in PVEC. We
conclude that growth factors also stimulate ERalpha-mediated gene expression in
vascular cells, but find that this occurs via a MAP kinase-independent pathway
distinct from that reported previously in nonvascular cells.
PMID- 9637721
TI - Human circulating eosinophils secrete macrophage migration inhibitory factor
(MIF). Potential role in asthma.
AB - Macrophage migration inhibitory factor (MIF) is a potent proinflammatory mediator
that has been shown to potentiate lethal endotoxemia and to play a potentially
important regulatory role in human acute respiratory distress syndrome (ARDS). We
have investigated whether eosinophils are an important source of MIF and whether
MIF may be involved in the pathophysiology of asthma. Unstimulated human
circulating eosinophils were found to contain preformed MIF. Stimulation of human
eosinophils with phorbol myristate acetate in vitro yielded significant release
of MIF protein. For example, eosinophils stimulated with phorbol myristate
acetate (100 nM, 8 h, 37 degreesC) released 1,539+/-435 pg/10(6) cells of MIF,
whereas unstimulated cells released barely detectable levels (< 142 pg/10(6)
cells, mean+/-SEM, n = 8). This stimulated release was shown to be (a)
concentration- and time-dependent, (b) partially blocked by the protein synthesis
inhibitor cycloheximide, and (c) significantly inhibited by the protein kinase C
inhibitor Ro-31,8220. In addition, we show that the physiological stimuli C5a and
IL-5 also cause significant MIF release. Furthermore, bronchoalveolar lavage
fluid obtained from asthmatic patients contains significantly elevated levels of
MIF as compared to nonatopic normal volunteers (asthmatic, 797.5+/-92 pg/ml;
controls, 274+/-91 pg/ml). These results highlight the potential importance of
MIF in asthma and other eosinophil-dependent inflammatory disorders.
PMID- 9637722
TI - Phenylketonuria. The in vivo hydroxylation rate of phenylalanine into tyrosine is
decreased.
AB - In phenylketonuria (PKU), the enzyme phenylalanine hydroxylase is deficient,
resulting in a decreased conversion of phenylalanine (Phe) into tyrosine (Tyr).
The severity of the disease is expressed as the tolerance for Phe at 5 yr of age.
In PKU patients it is assumed that the decreased conversion of Phe into Tyr is
directly correlated with the tolerance for Phe. We investigated this correlation
by an in vivo stable isotope study. The in vivo residual hydroxylation was
quantitated using a primed continuous infusion of L-[ring- 2H5]Phe and L-[1
13C]Tyr and the determination of the isotopic enrichments of L-[ring-2H5]Phe, L
[ring-2H4]Tyr, and L-[1-13C]Tyr in plasma. Previous reports by Thompson and
coworkers (Thompson, G.N., and D. Halliday. 1990. J. Clin. Invest. 86:317-322;
Thompson, G.N., J.H. Walter, J.V. Leonard, and D. Halliday. 1990. Metabolism.
39:799-807; Treacy, E., J.J. Pitt, K. Seller, G.N. Thompson, S. Ramus, and R.G.H.
Cotton. 1996. J. Inherited Metab. Dis. 19:595- 602), applying the same technique,
showed normal in vivo hydroxylation rates of Phe in almost all PKU patients.
Therefore, our study was divided up in two parts. First, the method was re
evaluated. Second, the correlation between the in vivo hydroxylation of Phe and
the tolerance for Phe was tested in seven classical PKU patients. Very low (0.13-
0.95 micromol/kg per hour) and normal (4.11 and 6.33 micromol/kg per hour)
conversion rates were found in patients and controls, respectively. Performing
the infusion study twice in the same patient and wash-out studies of the labels
at the end of the experiment in a patient and control showed that the method is
applicable in PKU patients and gives consistent data. No significant correlation
was observed between the in vivo hydroxylation rates and the tolerances. The
results of this study, therefore, showed that within the group of patients with
classical PKU, the tolerance does not depend on the in vivo hydroxylation.
PMID- 9637723
TI - Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate-
dependent anion secretion by an autocrine/paracrine mechanism in gallbladder
epithelial cells.
AB - Ion and fluid transport across the biliary epithelium contributes to bile
secretion. Since endothelin (ET)-1 affects ion transport activities and is
released by human gallbladder- derived biliary epithelial cells in primary
culture, we examined the expression of ET peptides and ET receptors and the
influence of ET-1 on ion transport in this epithelium ex vivo. In freshly
isolated gallbladder epithelial cells, preproET-1, -2, and -3 mRNAs were detected
by reverse transcription PCR and ET-1 isopeptide was identified by
chromatography. The cells also displayed ET receptor mRNAs and high-affinity
binding sites for ET-1, mostly of the ETB type. Electrogenic anion secretion
across intact gallbladder mucosa was stimulated by forskolin, secretin, and
exogenous ATP, as assessed by short-circuit current (Isc) increases in Ussing
type chambers. ET-1 inhibited forskolin- and secretin-induced changes in Isc,
without affecting baseline Isc or ATP-induced changes. Accordingly, ET-1
significantly reduced the accumulation of intracellular cAMP elicited by
forskolin and secretin in the epithelial cells, and this effect was abolished by
pertussis toxin. This is the first evidence that ET-1 is synthesized and
inhibits, via a Gi protein-coupled receptor, cAMP-dependent anion secretion in
human gallbladder epithelium, indicating a role in the control of bile secretion
by an autocrine/paracrine mechanism.
PMID- 9637724
TI - Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants.
Influence of Fas-mediated apoptosis.
AB - Based on successful induction of donor-specific unresponsiveness by alloantigenic
stimulation in several animal models of acute rejection, we hypothesized that
similar immune manipulations would also inhibit the evolution of chronic
rejection and transplant vasculopathy. To induce immune tolerance, DA rats
received a PVG heart allograft and were immunosuppressed with cyclosporine for 30
d. At day 100 the animals were challenged with a PVG aortic allograft after
either 1 or 18 h of cold ischemia. 8 wk after the aortic transplantation, the
grafts were investigated for morphological changes, infiltrating cells,
apoptosis, and Fas-Fas ligand expression. Control allografts showed advanced
transplant arteriosclerosis, whereas tolerance-induced aortic allografts
displayed reduced neointimal formation, less medial atrophy, fewer apoptotic
cells, and fewer Fas- and FasL-expressing cells. Prolonged ischemic storage time
did not profoundly alter the morphological changes of the allografts. Fas
expression was found in T cells, macrophages, vascular smooth muscle cells, and
endothelial cells, whereas FasL was expressed mainly by T cells and macrophages.
FasL mRNA expression was evident throughout the entire allograft wall. In
conclusion, induction of allospecific tolerance can effectively prevent
transplant arteriosclerosis. Cold ischemia damage does not abrogate the
beneficial effect of tolerance, but creates a separate identity of mainly
endothelial lesions. Furthermore, Fas-mediated apoptosis appears to be involved
in the pathological lesions seen in chronic rejection.
PMID- 9637725
TI - A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic
reticulum/proteasome degradation.
AB - Myeloperoxidase (MPO) deficiency is a common inherited disorder linked to
increased susceptibility to infection and malignancy. We identified a novel
missense mutation in the MPO gene at codon 173 whereby tyrosine is replaced with
cysteine (Y173C) that is associated with MPO deficiency and assessed its impact
on MPO processing and targeting in transfectants expressing normal or mutant
proteins. Although the precursor synthesized by cells expressing the Y173C
mutation (MPOY173C) was glycosylated, associated with the molecular chaperones
calreticulin and calnexin, and acquired heme, it was neither proteolytically
processed to mature MPO subunits nor secreted. After prolonged association with
calreticulin and calnexin in the endoplasmic reticulum, MPOY173C was degraded.
Furthermore, the 20S proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L
norleucinyl inhibited its degradation, suggesting that the proteasome mediates
proteolysis of MPOY173C and, thus, participates in quality control in this novel
form of hereditary MPO deficiency.
PMID- 9637726
TI - Polyclonal antibody directed against human RANTES ameliorates disease in the
Lewis rat adjuvant-induced arthritis model.
AB - Adjuvant-induced arthritis (AIA) is one of many animal models of rheumatoid
arthritis, a disease characterized by a T-lymphocyte and macrophage cellular
infiltrate. We have characterized the development of this disease model with
respect to chemokine expression. Increased levels of two chemokines, RANTES, a T
lymphocyte and monocyte chemo-attractant, and KC a chemoattractant for
neutrophils, were found in whole blood and in the joint. Surprisingly, levels of
MIP-1alpha, another T-lymphocyte and monocyte chemoattractant, were unchanged
throughout the course of the disease in whole blood and only slightly elevated in
the joint. RANTES expression plays an important role in the disease since a
polyclonal antibody to RANTES greatly ameliorated symptoms in animals induced for
AIA and was found to be as efficacious as treatment with indomethacin, a non
steroidal anti inflammatory. Polyclonal antibodies to either MIP-1alpha or KC
were ineffective. This is the first report to show the importance of RANTES in
the development of AIA.
PMID- 9637727
TI - Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene
treated guinea pigs.
AB - To test the inducibility of CYP1A homologs in guinea pig adrenal, the effects of
3,3'-methylcholanthrene, an archetypal inducer of CYP1A, were compared in guinea
pig adrenal and liver. Western blot analysis showed that levels of both CYP1A1
(53 kDa) and CYP1A2 (56 kDa) increasedin liver microsomes of 3,3'
methylcholanthrene-treated guinea pigs. In adrenals, an immunoreactive protein
comigrating with liver CYP1A1 was detected only after 3,3'-methylcholanthrene
treatment. Protein comigrating with CYP1A2 was never detected in adrenal
microsomes. A third inducible immunoreactive protein (57 kDa) was seen in liver,
but not adrenal, after 3, 3'-methylcholanthrene treatment. Another immunoreactive
protein (52 kDa), present constitutively in liver and adrenal microsomes, was not
induced in either tissue by 3,3'-methylcholanthrene. The precise identities of
the inducible 57-kDa and the noninducible 52-kDa proteins remain to be
determined. However, the identity of the 53-kDa protein in the adrenal as CYP1A1
was confirmed by RT-PCR, Northern blot, and sequence analysis. Similar analyses
demonstrated that, despite the fact that the 56-kDa protein was not detectable in
adrenal microsomes, CYP1A2 mRNA was present in adrenals of control animals.
Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following
3,3'-methylcholanthrene treatment, underscoring differences in the regulation of
CYP1A expression in the two tissues. Levels of ethoxyresorufin and
methyoxyresorufin metabolism correlated with levels of CYP1A1 and CYP1A2 protein,
respectively.
PMID- 9637728
TI - Two unusual amino acid substitutions in cytochrome b of the colorless alga
Polytomella spp.: correlation with the atypical spectral properties of the bH
heme.
AB - The dithionite-reduced spectra of the purified bc1 complexes from the colorless
alga Polytomella spp. and the closely related green alga Chlamydomonas
reinhardtii were compared. The spectrum of the bc1 complex from C. reinhardtii
showed a profile similar to those of the bc1 complexes from other species. In
contrast, the bc1 complex from Polytomella spp. exhibits a double-peak spectrum
in the alpha-band region, where the absorption bands of cytochrome c1 and
cytochrome b are completely resolved. To further understand the molecular basis
of these spectroscopic differences, the mitochondrial gene encoding cytochrome b
of Polytomella spp. was cloned, sequenced, and compared with that of C.
reinhardtii. The Polytomella spp. cytochrome b gene is 1113 bp long and does not
contain introns. The deduced protein sequence exhibits 56% identity and 68%
similarity with the cytochrome b of C. reinhardtii, and in a phylogenetic
analysis it clearly affiliated with the b-type cytochromes of C. reinhardtii and
C. smithii. A comparison of the primary sequences of the Polytomella spp.
cytochrome b with other b-type cytochromes, and its analysis based on the
structure featuring eight transmembrane stretches, allowed the identification of
a tyrosine in position 114, which substitutes for a tryptophan present in all
mitochondrial b-type cytochromes sequenced to date. In addition, the primary
sequence of the cytochrome b from Polytomella spp. has a serine at position 36,
instead of a nonpolar residue (alanine or leucine) found in all other species. In
the proposed model for cytochrome b, both residues Tyr114 and Ser36 are in close
proximity to the high-potential bH heme. The above data suggest that the polar
residues Y114 and S36, each one by itself or in combination, may interact with
heme bH of Polytomella spp. and, thus, may be responsible for the unique
spectroscopic characteristics of cytochrome b.
PMID- 9637729
TI - Role of allosteric: zinc interdomain region of the regulatory subunit in the
allosteric regulation of aspartate transcarbamoylase from Escherichia coli.
AB - The hydrophobic interface between the allosteric and the zinc domains of the
regulatory subunit of aspartate transcarbamoylase has previously been implicated
in the heterotropic ATP activation of the enzyme. The present work shows that
this interface also affects CTP and CTP-UTP inhibition and proposes a structural
explanation for the effects. Mutant enzymes derived from nonselective mutagenesis
of residues r101-r106 (residues that contribute part of the interface) displayed
a variety of homotropic and heterotropic effects. The cooperative behavior of the
enzymes was affected, as indicated by reduced aspartate S0.5 values and apparent
Hill coefficient values for V106L, V106L/N105S, and I103F/R102C. In addition,
both ATP activation and CTP inhibition were significantly reduced and CTP+UTP
synergistic inhibition was decreased in these mutants. The D104G mutant enzyme
was subject to inhibition by CTP andCTP+UTP, but was not activated by ATP.
Finally, the I103T mutant enzyme had an increased S0.5 value of 11.5 mM and
displayed altered effector responses: ATP acted as an inhibitor, and the CTP+UTP
synergistic inhibition was reduced. Most of these allosteric variations can be
explained in terms of perturbations to the "tongue and groove" hydrophobic
interface between the allosteric and the zinc domains and a consequent impact on
a second interface ("reg1:cat4") between regulatory and catalytic subunits.
PMID- 9637730
TI - Inhibition of protein tyrosine phosphatases PTP1B and CD45 by sulfotyrosyl
peptides.
AB - Sulfotyrosyl peptides corresponding to the known high-affinity substrate
phosphotyrosyl peptide sequences in casein and the autophosphorylation sites of
insulin receptor and EGF receptor were investigated as inhibitors of protein
tyrosine phosphatases PTP1B and CD45. These peptides inhibit both PTP1B and CD45
in the micromolar range competitively and reversibly. The elements required for
inhibition were investigated by truncation and substitution of these peptides.
Acidic residues N-terminal to the sulfotyrosyl residues are essential for high
affinity binding to PTP1B. The recognition elements required for inhibition of
PTP1B and CD45 are different and this suggests the possibility of identifying
selective active-site-directed inhibitors for these enzymes.
PMID- 9637731
TI - Purification, characterization, and amino acid sequence determination of
acanthins, potent inhibitors of platelet aggregation from Acanthophis antarcticus
(common death adder) venom.
AB - Venom of Acanthophis antarcticus, a common death adder, exhibits potent
antiplatelet effects. By a combination of gel-filtration, cation-exchange, and
reversed-phase chromatographic methods, two inhibitors of platelet aggregation,
named acanthin I and II, were purified to homogeneity as assessed by capillary
electrophoresis and electrospray mass spectrometry. These isoforms exhibit the
most potent antiplatelet activity known thus far, with IC50 values of 7 nM for
acanthin I and 4 nM for acanthin II in human whole blood when collagen was used
as an agonist, whereas with ADP the IC50 values were 10 and 12 nM, respectively.
Acanthin I and II are basic proteins with pIs of 10.2 +/- 0.1 and 10.4 +/- 0.1
and molecular weights of 12,844.58 +/- 0.61 and 12,895.63 +/- 0.48, respectively,
as determined by electrospray mass spectrometry. They exhibit phospholipase
enzyme activity, and acanthin I and II hydrolyzed 51. 57 +/- 1.30 and 46.85 +/-
2.90 micromol of phosphatidylcholine/min/mg, respectively. The complete amino
acid sequences of acanthin I and II showed that they have a high homology with
each other and with other elapids' phospholipase A2 neurotoxin, especially
pseudexin A.
PMID- 9637732
TI - Isolation, sequence analysis, and biological activity of atrolysin E/D, the non
RGD disintegrin domain from Crotalus atrox venom.
AB - Crotalid snake venom metalloproteinases often have associated with them
nonproteinase domains that may be processed from the mature proteinases. Nascent
atrolysin E, from the western diamondback rattlesnake, Crotalus atrox, has a
metalloproteinasedomain and a non-RGD disintegrin domain that is lacking in the
mature metalloproteinase. In this studywe report on the isolation, sequence
analysis, andbiological activity of the 7.4-kDa atrolysin E disintegrin domain
(atrolysin E/D). Atrolysin E/D represents approximately 0.2% of the total protein
fromthe crude venom. The protein begins with a glycinyl residue found in the
latter part of the spacer region. The sequence of atrolysin E/D is identical to
thatof the non-RGD disintegrin domain of atrolysin E. The structure is termed a
non-RGD disintegrin sincein lieu of the characteristic RGD sequence, a Met-Val
Asp (MVD) is found instead. Nevertheless, the protein is a potent inhibitor of
both collagen- and ADP-stimulated platelet aggregation with IC50 values of 4 and
8 nM, respectively. A cyclized synthetic peptide, Ac-CRVSMVDRNDDTC-NH2, which
represents the sequence of the atrolysin E/D non-RGD loop, was demonstrated to be
an effective inhibitor of platelet aggregation. Therefore, this region of
atrolysin E/D's structure, as in the disintegrins proper, is important for the
biological activity of the protein. Thus, like the non-RGD disintegrin barbourin
from Sistrurus miliarius barbouri, a RGD sequence in the context of the
disintegrin protein backbone is not an absolute requirement for platelet
aggregation inhibitory activity. These data underscore the biochemical and
functional complexity of crotalid snake venoms due to differential proteolytic
processing of the precursor metalloproteinases and exemplify how the processed
fragments may contribute to the observed pathological effects of the venom.
PMID- 9637733
TI - Expression and characterization of human glutamate-cysteine ligase.
AB - Glutamate-cysteine ligase (GLCL) catalyzes the rate-limiting step in glutathione
biosynthesis. GLCL comprises regulatory (GLCLR) and catalytic (GLCLC) subunits.
To understand better the structure-function relationship of GLCL subunits and
holoenzyme, human GLCLR and GLCLC genes were inserted into the baculovirus
genome. Recombinant hGLCLR andhGLCLC were produced in cells infected with
recombinant baculoviruses, and homogeneous hGLCL subunits and holoenzyme were
purified from cell lysates with a Ni-NTA resin. Purified recombinant hGLCL
holoenzyme was catalytically more active than hGLCLC with L-glutamate, L-alpha
aminobutyrate, and ATP as substrates. The selectivity of purified hGLCL
holoenzyme for L-glutamate, L-alpha-aminobutyrate, or L-cysteine was
significantly higher than for hGLCLC. Glutathione was a noncompetitive inhibitor
for both hGLCL holoenzyme and hGLCLC. hGLCLC was more sensitive to inhibition by
glutathione than hGLCL holoenzyme. Deletion of the first 25 amino acid residues
at the amino terminus of GLCLC dramatically decreased GLCL activity, indicating
that the amino terminus of GLCLC is required for full catalytic activity.
Expressed and purified hGLCL provides a useful tool to investigate glutathione
biosynthesis in vitro.
PMID- 9637734
TI - cAMP does not inhibit convulxin-induced tyrosyl-phosphorylation of human platelet
proteins, including PLCgamma2, but completely blocks the integrin alphaIIb beta3
dependent dephosphorylation step: comparisons with RGDS peptide, cytochalasin D,
and phenylarsine oxide.
AB - Convulxin (Cvx) isolated from Crotalus durissus terrificus venom, induces
platelet aggregation, phospholipase C (PLC) activation, and tyrosyl
phosphorylation (PTP) of multiple proteins, including PLCgamma2 by a mechanism
independent of integrin alphaIIb beta3. However, PTP induced by Cvx is followed
by a dephosphorylation step in a platelet aggregation-dependent manner. Here we
show that increasing intraplatelet content of cAMP with forskolin is associated
with the inhibition of Cvx-induced platelet aggregation, ATP secretion, and
inositol-phosphates production. However, the early onset of Cvx-induced PTP is
not sensitive to cAMP (including PLCgamma2), and it also occurs in the presence
of integrin alphaIIb beta3-antagonist (RGDS peptide, RGDS) or inhibitors of actin
polymerization (cytochalasin D, CD) and tyrosine-phosphatases (phenylarsine
oxide, PAO). However, forskolin, RGDS, and CD prevented the dephosphorylation
step together with inhibition of platelet aggregation, whereas in the presence of
phenylarsine oxide (PAO) the dephosphorylation step was replaced by an increase
in the number and intensity of tyrosyl-phosphorylated proteins. Our data provide
evidence to conclude that (i) cAMP inhibits platelet aggregation at a downstream
site to PLCgamma2 tyrosyl-phosphorylation; (ii) Cvx-induced PTP is independent on
integrin alphaIIb beta3 engagement, actin polymerization, and tyrosine
phosphatases activation; (iii) integrin alphaIIb beta3 mediates the
dephosphorylation step in a platelet aggregation-dependent manner; and (iv) Cvx
and collagen stimulate platelets by a similar signal transduction pathway.
PMID- 9637735
TI - Reasoning enantioselectivity and kinetics of seleno-subtilisin from the
subtilisin template.
AB - The active-site serine (Ser221) of subtilisin Carlsberg(from Bacillus
licheniformis) and subtilisin BPN' (fromBacillus amyloliquefaciens) was
chemically converted into a selenocystein. Contrary to subtilisin's protease
activity the semisynthetic seleno-subtilisin catalyzed the reduction of
hydroperoxides. Enantioselectivity and kinetics of this reaction were studied by
kinetic resolution of five racemic alkyl aryl hydroperoxides catalyzed by the
seleno-subtilisin variants. Due to the identical tertiary structure of subtilisin
and seleno-subtilisin, the enzymes have comparable substrate binding properties.
Thus, a rational screening for suitable peroxidase substrates featuring
structural characteristics of known subtilisin substrates was enabled. The
enantioselective recognition of (S)-configured alkyl aryl hydroperoxides by
seleno-subtilisin was comprehensible by subtilisin's preference for comparable
(S)-alkyl aryl amines or alcohols. The analysis of chiral products by
multidimensional gas chromatography revealed enantiomeric excesses up to 98%.
Kinetics of seleno-subtilisin were rationalized on the basis of the established
substrate-catalyst interactions of the subtilisin framework. The Carlsberg and
BPN' peroxidase variants revealed typical differences in turnover numbers (kcat)
and Michaelis-Menten affinity constants (Km) already known from subtilisin
variants. Turnover numbers of seleno-subtilisin BPN' were lower and Km values
were higher in comparison to Carlsberg variant. Substrate affinity of several
substituted 1-arylethyl hydroperoxides to seleno-subtilisin was reasonable in
comparison to corresponding aryl boronic acid inhibitors of subtilisin.
PMID- 9637736
TI - An examination of the role of increased cytosolic free Ca2+ concentrations in the
inhibition of mRNA translation.
AB - Mobilization of Ca2+ sequestered by the endoplasmic reticulum (ER) produces the
phosphorylation of initiation factor (eIF) 2, whereas an increase in cytosolic
free Ca2+ ([Ca2+]i) due to plasmalemmal Ca2+ influx increases the phosphorylation
of elongation factor (eEF) 2. In nucleated mammalian cells, depletion of ER Ca2+
stores has been demonstrated to inhibit translational initiation, but evidence
that increased [Ca2+]i per se causes slowing of peptide chain elongation is
lacking. L-type Ca2+ channel activity of GH3 pituitary cells, which are enriched
in calmodulin-dependent eEF-2 kinase, was manipulated such that the impact of
[Ca2+]i on eEF-2 phosphorylation and translational rate could be examined for up
to 10 min without inhibiting initiation. At 1 mM extracellular Ca2+, resting
[Ca2+]i values were high (154-255 nM) and eEF-2 was phosphorylated. The Ca2+
channel antagonist, nisoldipine, lowered [Ca2+]i and reduced eEF-2
phosphorylation by half but had no effect on amino acid incorporation. The Ca2+
channel agonist, Bay K 8644, produced sustained elevations of [Ca2+]i that were
associated with 25-50% increases in eEF-2 phosphorylation, but no changes in
protein synthetic rates occurred. Larger Ca2+ influxes were achievable with
either 25 mM KCl or KCl plus Bay K 8644. These treatments further increased eEF-2
phosphorylation (50-100% above control) and inhibited leucine incorporation by 20
70% but ATP content was reduced by 25-50% and total cell-associated Ca2+ contents
rose by 3- to 13-fold. eIF-2alpha was not phosphorylated during these treatments.
Addition of low concentrations of ionomycin, which do not lower ATP content, was
associated with complex changes in [Ca2+]i that resembled alterations in eEF-2
phosphorylation. The inhibition of leucine incorporation in response to
ionomycin, however, coincided only with the phosphorylation of eIF-2alpha, not
eEF-2. It is concluded that changes in [Ca2+]i occurring in the absence of ATP
depletion alter the phosphorylation state of eEF-2 but are not regulatory for
mRNA translation.
PMID- 9637737
TI - The PutA protein of Salmonella typhimurium catalyzes the two steps of proline
degradation via a leaky channel.
AB - Proline utilization in Salmonella typhimurium requires two proteins encoded by
the put operon: PutP, the major proline permease, and PutA. PutA is a
multifunctional, peripheral membrane protein which acts both as a transcriptional
repressor for the put operon and enzyme catalyzing the two-step conversion of
proline to glutamate. In the first enzymatic reaction catalyzed by PutA, proline
oxidation to pyrroline-5-carboxylate (P5C) is coupled with the reduction of a
tightly associated FAD. In the second reaction, P5C oxidation to glutamate is
coupled with reduction of soluble NAD. Although PutA can use exogenous P5C, the
concentration of exogenous P5C required for the P5C dehydrogenase reaction is
much greater than the steady-state P5C concentration accumulated during proline
degradation. Furthermore, exogenous P5C does not efficiently compete against
endogenous P5C for the production of glutamate, and the endogenous P5C produced
directly from proline is preferentially used by PutA for the production of
glutamate. Kinetic assays indicate that in the presence of NAD the two enzymatic
reactions of PutA function synchronously to increase the overall reaction rate
over that of the two independent reactions, and the second reaction proceeds in
the absence of a lag phase. These results indicate that PutA directly transfers
the intermediate P5C between the two enzymatic functions via a "leaky channel"
mechanism. Because both the reduction of FAD and the intermediate P5C stimulate
membrane association of PutA, channeling of P5C may also contribute to the
regulation of proline utilization.
PMID- 9637738
TI - High-level expression of RXRalpha and the presence of endogenous ligands
contribute to expression of a peroxisome proliferator-activated receptor
responsive gene in hepatoma cells.
AB - Genes containing peroxisome proliferator-activated receptor (PPAR) binding sites
are both inducible by peroxisome proliferators and expressed in a tissue-specific
fashion. A PPAR-responsive reporter gene cotransfected with a PPARalpha
expression vector was highly expressed in H4IIEC3 hepatoma cells. Addition of
clofibrate resulted in a modest further induction of the reporter gene. In CV-1
cells, high expression of the reporter required the addition of clofibrate.
H4IIEC3 cells had higher levels of retinoid X receptor (RXRalpha) than CV-1
cells; cotransfection of CV-1 cells with PPARalpha plus RXRalpha expression
plasmids abolished the cell line difference in basal and clofibrate-stimulated
expression of the reporter. Lipid extracts of hepatoma cells or of liver or
kidney stimulated expression of the reporter; extracts of CV-1 cells were far
less effective. Chromatographic analysis of these extracts revealed high levels
of three fractions of lipid in liver and H4IIEC3 cells that were lower in CV-1
cells. We conclude that (1) in cells expressing high levels of both RXRs and
PPARalpha, such as hepatocytes and kidney cells, these factors are constitutively
active; (2) activators of PPARalpha may increase its ability to form heterodimers
with RXRs when the latter are limiting; and (3) hepatoma cells, liver, and kidney
contain lipid-extractable compounds capable of activating PPARalpha.
PMID- 9637739
TI - Mechanism-based inactivation of cytochromes P450 2E1 and 2B1 by 5-phenyl-1
pentyne.
AB - A series of acetylenic compounds whose structures were based on "P450 2E1-like"
substrates was investigated for their ability to cause inactivation of P450 2E1
dependent p-nitrophenol hydroxylation. The most effective compound with liver
microsomes from pyridine-treated rats or with rabbit P450 2E1 in a reconstituted
system was 5-phenyl-1-pentyne. The inactivation of purified 2B1, 2E1, a truncated
2E1 lacking amino acids 3-29, 2E1(Delta3-29), or a truncated 2E1 in which
threonine 303 was replaced with alanine, 2E1(Delta3-29, T303A), in a
reconstituted system by 5-phenyl-1-pentyne was NADPH- and time-dependent and
followed pseudo-first-order kinetics. The maximal rate constants for
inactivation, the concentrations that gave half-maximal inactivation (KI), and
the partition ratios (the number of 5-phenylvaleric acid molecules
formed/inactivation event) were determined with each P450. The KI values for 2B1
and 2E1(Delta3-29, T303A) were twice those for 2E1 and 2E1(Delta3-29), and the
partition ratios for 2B1 and 2E1(Delta3-29, T303A) were 5-10 times greater than
those of 2E1 or 2E1(Delta3-29). During the incubation of P450 2E1 with 5-phenyl-1
pentyne, the loss of P450 as determined by the reduced-CO difference spectra was
equal to the loss of catalytic activity. The formation of a heme adduct was
demonstrated by HPLC analysis of reaction mixtures containing 5-[3H]phenyl-1
pentyne. HPLC analysis with diode-array detection showed that the Soret region of
the proposed heme adduct was different from that of the unmodified heme. The HPLC
peak containing the proposed heme adduct was further analyzed by matrix-assisted
laser desorption ionization mass spectrometry, and the resulting peaks could
result from the addition of a 2-oxo-5-phenylpentyl group to the heme.
PMID- 9637740
TI - Accumulation of various N-acylethanolamines including N-arachidonoylethanolamine
(anandamide) in cadmium chloride-administered rat testis.
AB - Changes in the levels of various molecular species of N-acylethanolamine in CdCl2
administered rat testis were examined. We found that the levels of various N
acylethanolamines including anandamide (N-arachidonoylethanolamine), an
endogenous cannabinoid receptor ligand, were dramatically increased in CdCl2
admin-istered rat testis. Such changes were particularlyprominent for saturated
and monoenoic species such as N-palmitoyl species (39-fold at 9 h) and N-stearoyl
species (21-fold at 9 h), compared with unsaturated fatty acid-containing species
such as anandamide (5-fold at 9 h). Noticeably, increased levels were observed of
not only N-acylethanolamines but also several species of N
acylphosphatidylethanolamine, potential precursors for N-acylethanolamines. We
confirmed that the rat testis microsomal fraction contains phosphodiesterase
activity catalyzing the release of N-acylethanolamine from N
acylphosphatidylethanolamine and transacylase activity catalyzing the formation
of N-acylphosphatidylethanolamine from phosphatidylethanolamine and
phosphatidylcholine. These enzyme activities were not dramatically different in
the microsomal fraction obtained from CdCl2-administered rat testis compared with
that in the case of control rat testis, at least when estimated in cell-free
assay systems, suggesting that the accessibility of the substrates to the enzymes
may be increased in CdCl2-administered rat testis to generate a large amount of N
acylethanolamine. Possible pathophysiological implications of the augmented
generation of N-acylethanolamine including anandamide in CdCl2-administered rat
testis were discussed.
PMID- 9637741
TI - Radiation inactivation suggests that human multidrug resistance-associated
protein 1 occurs as a dimer in the human erythrocyte membrane.
AB - Molecular masses of functional units of two components of 2, 4-dinitrophenyl-S
glutathione (DNP-SG) transport across the erythrocyte membrane determined by
radiation inactivation were 437 +/- 69 kDa for the high-affinity component and
466 +/- 67 kDa for the low-affinity component. These results confirm that the
multidrug resistance-associated protein (MRP) 1 is responsible for the high
affinity DNP-SG transport across the erythrocyte membrane and suggest that MRP1
exists in the membrane as a dimer. The molecular size of the low-affinity
transporter is similar if not identical to that of MRP1. Moreover, while the
molecular mass of the DNP-SG-ATPase activity of the erythrocyte membrane
corresponds also to that of MRP (375 +/- 36 kDa), the molecular mass of the
functional unit of dinitrophenol-stimulated ATPase is significantly lower (232 +/
26 kDa), which suggests that thisactivity is linked to a different protein,
perhapsaminophospholipid translocase.
PMID- 9637742
TI - Dietary cholesterol regulates hepatic 3-hydroxy-3-methylglutaryl coenzyme A
reductase gene expression in rats primarily at the level of translation.
AB - The level of gene expression at which dietary cholesterol exerts feedback
regulation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
was investigated using young male Sprague-Dawley rats. Previous studies suggested
that this regulation might be exerted posttranscriptionally. Thus, possible
regulation at the levels of catalytic efficiency, protein turnover, and
translation was investigated. To examine possible regulation at the level of
catalytic efficiency, rats were placed on chow diets supplemented with 2%
cholesterol and the rates of decline in hepatic HMG-CoA reductase activity and
immunoreactive protein levels were determined. Both decreased slowly over a 72-h
period. The catalytic efficiency did not change. These observations are
inconsistent with phosphorylation-dephosphorylation or thiol-disulfide
interchange as possible mechanisms. The possibility that dietary cholesterol
might act by increasing the rate of turnover of HMG-CoA reductase protein was
examined by determining the half-life of the enzyme in livers from rats consuming
chow or chow supplemented with 2% cholesterol. The half-life of HMG-CoA reductase
protein was not decreased in the animals receiving cholesterol, thus ruling out
this possibility. Regulation at the level of translation was investigated by
measuring the rate of HMG-CoA reductase protein synthesis in liver slices using
[35S]methionine and [35S]cysteine. It was found that the rate of synthesis was
reduced by over 80% in liver slices from rats fed a diet supplemented with 2%
cholesterol. Similar results were obtained with liver slices from rats given
mevalonolactone, which supplies both sterol and nonsterol endproducts. These
results indicate that cholesterol regulates hepatic HMG-CoA reductase gene
expression in rats primarily at the level of translation.
PMID- 9637743
TI - NF-AT-luciferase reporter T cell lines as tools to screen immunosuppressive
drugs.
AB - The development of safer analogues of immunosuppressants such as cyclosporin A
and FK506 is an important goal for a number of clinical applications ranging from
transplantation to the treatment of autoimmune diseases. Here we show the
generation and the characterization of Jurkat T cell lines stably transfected
with a reporter construct containing the firefly luciferase gene under the
control of NF-AT. These lines specifically respond in a cyclosporin A-sensitive
manner to T cell antigen receptor-derived signals. Due to the high levels of
luciferase activity expression fewer than 1000 cells are required for detection
of luciferase. In addition, a simplified luciferase assay allows to reduce both
the manipulations and the time required for the assay, making these lines
potentially useful models for the automated screening of cyclosporin A and FK506
analogues.
PMID- 9637744
TI - Evaluation of the safety and immunogenicity of a new, heat-treated human rabies
immune globulin using a sham, post-exposure prophylaxis of rabies.
AB - A double-blind, controlled, randomized trial was conducted to evaluate the safety
and immunogenicity of a new human rabies immune globulin (HTRIG). This product,
manufactured by Pasteur Merieux Connaught, PMC, has undergone a heat-treatment
step (10 h at 60 degrees C) and removal of mercurothiolate. The corresponding
unheated product available from the same manufacturer (human rabies immune
globulin, HRIG, IMOGAM RABIES[spr2]) was used for comparison. These two rabies
immune globulins (RIGs) were administered either alone or in association with the
human diploid cell rabies vaccine (HDCV, IMOVAX[spr2] RABIES, PMC) according to a
standard, post-exposure rabies prophylaxis schedule. Sixty-four healthy adults
were randomly assigned to four groups of 16 to receive either HRIG/placebo,
HTRIG/placebo, HRIG/HDCV or HTRIG/HDCV. RIG was administered at the recommended
dose of 20 IU/kg by three intramuscular (i.m.) injections in the gluteus. HDCV or
placebo was given on day (D) 0, D3, D7, D14, and D28 into the deltoid by the
intramuscular (i.m.) route. Any local reaction from D0 to D3 at the immune
globulin injection site, and any systemic reaction from D0 to D42, were monitored
by subject diaries. Rabies-neutralizing serum antibody levels were assessed by
the rapid fluorescent focus inhibition test (RFFIT) before treatment and on D3,
D7, D14, D28, D35, and D42. No serious adverse reactions and, in particular, no
allergic-type reactions were reported. The safety profiles of HTRIG and HRIG were
similar, except that complaints of pain, or tenderness at the injection site were
half as common in the HTRIG group. Most of the local reactions were mild or
moderate. After the administration of HTRIG/placebo or HRIG/placebo, 60% of
subjects had detectable rabies antibodies levels, but by D42 all titres were
below the seroprotective level (i.e. below 0.5 IU/ml). In the groups HTRIG/HDCV
and HRIG/HDCV, the antibody titres rose markedly from D7, and reached a maximum
value of 19 IU/ml (95% CI, 11 to 38 IU/ml) and 31 IU/ml (95% CI, 20 to 48 IU/ml),
respectively, on day 14. All subjects who received RIG and vaccine maintained a
protective antibody level from D14 to D42. No significant difference in
immunogenicity results between these two groups (HTRIG/HDCV and HRIG/HDCV) was
observed, and no interference of immune globulin with vaccine was reported. The
safety and immunogenicity profiles of PMC HTRIG appear comparable with the
current reference product. The heat-treatment step will enhance the safety by
further reducing the probability of virus transmission through immune globulin
treatment. The low levels of rabies antibodies obtained by intramuscular
administration of either PMC HTRIG or of PMC HRIG support the recommendations
that call for local infiltration of wounds with RIG.
PMID- 9637745
TI - Studies on the loss of infectivity of live type 3 poliovaccine on storage.
AB - The Children's Vaccine Initiative established a Product Development Group in 1991
to help in the development of oral poliovaccines of improved thermostability.
Under the auspices of this group, the effect of different stabilizers on the loss
of infectivity of commercial monovalent type 3 live poliovaccine bulks at 37
degrees C, 42 degrees C and 45 degrees C has been examined. The only effective
conditions were the maintenance of the pH at 6.5, and the use of deuterium oxide
at a concentration of 90%. All other additives, including detergents, albumin,
antiviral compounds, sucrose and magnesium chloride, alone or in combination
either had no effect or increased the rate of loss of infectivity.
PMID- 9637746
TI - Stepwise iodination. A general procedure for detoxification of proteins suitable
for vaccine development and antiserum production.
AB - By gradual incorporation of stable iodine into toxins and whole venoms it is
possible to abolish completely the lesion and lethal properties of the native
components. Allergen extracts can be turned anallergic. Physiological proteins
with strong biological activity can also be rendered innocuous. Tyrosine and
histidine are the reactive groups that incorporate the hapten. Within the same
batch of protein, there is a defined ratio hapten/protein to achieve the desired
modified properties of the derivative. The iodinating solutions are easily
prepared, can be accurately standardized and have unlimited shelf lives. The
derivatives are obtained in a short time. The cost of the entire procedure is
very low. The method was applied to tityustoxin and whole venom of the scorpion
Tityus serrulatus; crotoxin and whole venom of Crotalus durissus terrificus; to
five bothropic venoms; to allergenic extracts of Schistosoma mansoni; to cholera
and tetanus toxin; and to insulin, kallikrein and tonin. The derivatives obtained
were stable, did not show any reversion to toxicity, generated antibodies against
the native antigens and gave active protection when injected into animals. No
local or systemic side effects were observed, even after prolonged use. The
injections were also apparently painless. By extensive haptenization self
proteins can be rendered non-self, able to generate antibodies against both the
derivative and the native unmodified protein, and iodination was very convenient
for this purpose. A new schedule for immunization, only feasible with completely
toxoided venoms is presented. It is based on a clonal expansion induced by a
small dose, followed by an exponential saturation dose of the same toxoid. The
attainment of higher levels of antibodies against the native antigen, in the
generated sera is unmatched by other procedures.
PMID- 9637747
TI - A simple and rapid method for measuring unconjugated capsular polysaccharide
(PRP) of Haemophilus influenzae type b in PRP-tetanus toxoid conjugate vaccine.
AB - The authors developed a simple and rapid method for quantitation of free capsular
polysaccharide of Haemophilus influenzae type b (polyribosyl ribitol phosphate,
PRP) in PRP-tetanus toxoid conjugate vaccine based on acid precipitation of
tetanus toxoid (TT). Acid hydrolysis of PRP during the assay was not detected.
The conditions used in the assay did not precipitate unconjugated PRP or adipic
acid dihydrazide derivatized PRP. The method was highly reliable, reproducible
and sensitive. The accuracy of the assay was confirmed by spiking known amounts
of unconjugated PRP to PRP-TT conjugate preparations. A PRP-TT preparation,
incubated at 37 degrees C for 6 months showing most of the PRP as unconjugated
(87% determined by this method), was not immunogenic in mice for the PRP
component even after two injections. In contrast, the same preparation held at 4
degrees C for 20 months, showing 17% unconjugated PRP, induced IgG antibodies to
PRP which were boosted after second injection. Therefore, this method is very
useful to evaluate the stability of PRP-TT conjugate vaccine. The assay may be
useful for characterizing other polysaccharide-protein conjugate vaccines.
PMID- 9637748
TI - A universal virus inactivant for decontaminating blood and biopharmaceutical
products.
AB - Removal of virus infectivity from blood and biopharmaceutical products prepared
from blood is an issue of considerable importance. For biopharmaceutical
products, removal can usually be achieved by a series of fractionation steps or
by inactivation with a suitable reagent. Irrespective of the methods that are
chosen it is vital that the biological activity of the product is not impaired.
For blood and unfractionated plasma or serum, the problem is even more
challenging. Selective inactivation of the genome is the key step in the
preparation of killed virus vaccines. Viruses belonging to all the recognised
families can be inactivated by imines. In this paper it is shown that the
biological properties of several proteins, including the cell growth-promoting
factors in calf serum, are not impaired using conditions which ensure the
inactivation of > 10(15) infectious units of poliovirus and foot-and-mouth
disease virus (FMDV). Also shown is that both viruses can be inactivated by
imines at 4 degrees C, thus providing a method for removing infectivity from
protein preparations which are unstable at higher temperatures. The RNA extracted
from FMDV inactivated at 4 degrees C was not degraded and contained no hidden
breaks but nevertheless was non-infectious. However, it could be amplified by PCR
using primers corresponding to the gene coding for a portion of the viral RNA
polymerase, but not from that coding for VP1, one of the structural proteins,
showing that alteration of a base or bases had occurred in that region.
Surprisingly, it could be translated in the rabbit reticulocyte system although
some of the products were different from those obtained with unmodified RNA.
PMID- 9637749
TI - Gold, the noble metal and the paradoxes of its toxicology.
AB - Gold is possibly the most ancient and, in its recent incarnation as a delivery
vehicle for gene therapy, one of the most modern agents in all of medicine's
pharmacopoeia. Its administration to humans is both deliberate and inadvertent.
It is universally recognized as the most inert of metals, yet it can be
sensitizing. Gold's broadest clinical application (in rheumatoid arthritis)
derives from a premise that was totally flawed. It is employed clinically to
effect immune suppression yet it can engender toxicities that stem from
immunostimulation. To complete this series of paradoxes, the toxicity of gold,
unlike that of most pharmaceuticals, is, in general, not predictably related to
the levels it attains within bodily tissues. Accordingly, the pharmacology and
toxicology of gold is remarkably complex. Recent laboratory discoveries
concerning gold's metabolism, have emphasized the important metabolic differences
between its three oxidation states (0, I and III). When placed in the context of
a wealth of clinical experience, these discoveries provide useful insights into
its toxicology and shine a revealing light on the mechanisms which account for
its seemingly paradoxical behaviour.
PMID- 9637750
TI - A cell-based potency assay for insulin-like growth factor-I.
AB - The authors developed a cell-based bioassay for determining the potency of
recombinant human insulin-like growth factor I (IGF-I) using HU-3 human
megakaryoblastic cell line. Cell proliferation was measured using the alamarBlue
fluorescence method. The addition of IGF-I resulted in a dose-dependent growth
response after 48 hours under serum-free conditions. The effective range was 0.1
25 ng/ml with half-maximal response at approximately 2 ng/ml IGF-I. The assay is
simple, requiring just three steps, performed in 96-well microtitre plates and is
able to detect changes in activity of truncated analogues of IGF-I (such as des
Gly-IGF-I, des-Gly-Pro-IGF-I and des-Gly-Pro-Glu-IGF-I) as well as IGF-I samples
that had been subjected to proteolytic or disulfide reduction treatments. This
assay is precise, with interassay variability of less than 10% and accurate, with
percentage recoveries of nearly 100%. The relative efficacies of other insulin
related peptides in stimulating cell growth of the cell line were examined. IGF
II was 5-fold less potent than IGF-I and insulin had little or no proliferative
activity. In addition, the growth-promoting activity correlated well with IGF-I
stimulation of glucose consumption in this system. In conclusion, the HU-3 human
megakaryoblastic cell line constitutes a simple system for measuring the
biological activity of recombinant IGF-I in quality control set-up. The safety,
convenience and precision of the assay make it an attractive alternative to
radioactive and other colorimetric methods.
PMID- 9637751
TI - EPFA/NIBSC Workshop on Nucleic Acid Amplification Technology (NAT) for the
detection of blood borne viruses.
PMID- 9637754
TI - Sublexical Inferences in Beginning Reading: Medial Vowel Digraphs as Functional
Units of Transfer.
AB - Two experiments evaluated young children's use of lexical inference. Experiment 1
compared transfer from shared rimes (e.g., "beak"-"peak"), or heads (e.g., "beak"
"bean"), under three conditions: (a) when both clue word pronunciation and
orthography were present at transfer; (b) when only the pronunciation of the clue
word was given; and (c) when the clue was pretaught. Equivalent transfer occurred
in both conditions (a and b) where clue word pronunciations were provided at
transfer, but no transfer was found when the clue word was pretaught (condition
c). Experiment 2 investigated transfer from three pretaught clue words sharing
rimes (e.g., "leak"-"peak"), or vowel digraphs (e.g., "leak"-"bean"). Children
demonstrated lexical transfer under these conditions, but improvements were
equivalent for vowel and rime analogous words. Results are interpreted in terms
of models of vowel transfer. Copyright 1998 Academic Press.
PMID- 9637755
TI - Perceptual constraints on infant memory retrieval.
AB - In three experiments with 78 3-month-olds, we asked what determines whether or
not a stimulus will pop out and cue retrieval from long-term memory. All infants
were trained with mobiles displaying either Qs (feature-present stimuli) or Os
(feature-absent stimuli) and were tested 24 h later. When the diagonal line of
the Q bisected its rim, feature-absent stimuli controlled retrieval in tests with
homogeneous displays, and stimulus novelty controlled retrieval in tests with pop
out displays. A follow-up experiment revealed that the similarity between Q and O
determined whether or not Q popped out: When its tail projected externally from
the rim, Q popped out and cued retrieval, but O did not (search asymmetry). When
its tail projected internally from the rim, however, 3-month-olds failed to
discriminate Q from O (the externality effect). These data reveal that target
distractor similarity constrains whether or not a feature-present stimulus will
pop out and cue retrieval.
PMID- 9637756
TI - Intersensory redundancy facilitates learning of arbitrary relations between vowel
sounds and objects in seven-month-old infants.
AB - This study investigated 7-month-old infants' ability to relate vowel sounds with
objects when intersensory redundancy was present versus absent. Infants (N = 48)
were habituated to two alternating video-films of vowel-object pairs in one of
three conditions. In the moving-synchronous condition, where redundancy was
present, the movement of one object was temporally coordinated with the spoken
vowel /a/ and that of the other with /i/, simulating showing and naming the
objects to the infant. In the still and in the moving-asynchronous conditions,
where redundancy was absent, infants saw static objects, and objects moving out
of synchrony with the vowel sounds, respectively. The results indicated that
infants detected a mismatch in the vowel-object pairs in the moving-synchronous
condition but not in the still or the moving-asynchronous condition. These
findings demonstrate that temporal synchrony between vocalizations and the
motions of an object facilitates learning of arbitrary speech-object relations,
an important precursor to the development of lexical comprehension in infancy.
PMID- 9637759
TI - Differential mononuclear leukocyte attracting chemokine production after
stimulation with active and inactivated influenza A virus.
AB - After influenza A virus infection of human monocytes, we found a rapid and marked
release of the mononuclear cell attracting chemokines MCP-1, MIP-1 alpha, and IP
10, with corresponding gene expression patterns as determined by Northern blot
analysis. In striking contrast, the expression and release of the neutrophil
chemoattractant IL-8 was not inducible. To determine the underlying mechanisms
responsible for the induction of this differential chemokine pattern, we
stimulated monocytes with UV- and heat-inactivated (56 degrees C and 100 degrees
C) influenza A virus. In comparison with fully infectious influenza A, 56 degrees
C-inactivated virus induced a strong production of MCP-1, MIP-1 alpha, and IP-10,
while the release of MIP-1 alpha and IP-10 was substantially lower after exposure
to UV-inactivated virus. No chemokine expression was found after stimulation with
100 degrees C-inactivated influenza A virus. Our data indicate that, contingent
upon the chemokine examined, the maximal induction depends on the unrestricted
infectivity of the virus, the unaltered hemagglutinin molecule, or the intact
viral RNA. This diversified chemokine production may enable the infected host to
mount an efficient antiviral response against infective and noninfective virus
particles.
PMID- 9637760
TI - Immunological and pathological consequences of mutations in both Fas and Fas
ligand.
AB - The lpr mutation in mice results in premature termination of transcription of the
gene encoding the apoptosis-signaling receptor Fas. As a result, lpr mice develop
severe lymphoproliferation and lupus-like autoantibodies. Growing evidence
suggests that the lpr mutation is "leaky" and that low levels of Fas are
expressed in lpr mice. To determine if Fas expressed in lpr mice is contributing
to apoptosis we generated a novel strain of mice (B6/lprgld) which is homozygous
for both the lpr mutation and the gld mutation which encodes nonfunctional Fas
ligand (FasL) protein. If low levels of Fas in B6/lpr mice contribute to
apoptosis and lessen the severity of disease, the B6/lprgld mice, which also lack
functional FasL, would be expected to develop a more severe form of disease than
B6/lpr mice. Our results revealed no significant increase in either
lymphoproliferation or autoimmunity in B6/lprgld mice compared to B6/lpr or
B6/gld mice. Additionally, no increase in surface expression of Fas was detected
by flow cytometry on B6/lprgld lymphocytes compared to B6/lpr lymphocytes.
However, histological examination of B6/lprgld liver revealed a marked increase
in lymphocytic infiltration, compared to livers of B6/lpr and B6/gld mice. Our
results suggest that, while low levels of Fas in lpr mice may not be contributing
to amelioration of lymphoproliferation or autoimmunity, they may be partially
protecting the liver from abnormalities which arise in the absence of Fas
mediated apoptosis.
PMID- 9637761
TI - Dendritic cells internalize vaccine adjuvant after intramuscular injection.
AB - Vaccine adjuvants help antigens elicit rapid, potent, and long-lasting immune
responses. The lack of understanding of the immunological mechanism of action of
adjuvants has limited the rational development of vaccines for human use. In
particular, little is known about how the immune system processes adjuvants. The
goal of the present study was to determine the fate of the vaccine adjuvant MF59,
labeled with the fluorescent dye Dil, after injection with fluorescein-labeled
gD2 antigen from type 2 herpes simplex virus. At 3 h after intramuscular
injection into BALB/c mice, most of the MF59 was still in the form of
extracellular droplets in the muscle, but a detectable fraction of the MF59 was
in cells in the subcapsular sinus of draining inguinal lymph nodes. At 48 h, most
of the MF59 at the site of injection was inside cells that were immunoreactive
for the dendritic cell markers DEC-205 and MHC class II molecules, reflecting the
interaction of MF59 with antigen presenting cells. At this time, intracellular
MF59 was also abundant in the paracortical (T cell) region of lymph nodes. The
gD2 antigen was also intracellular in muscle and colocalized MF59 at 48 h, and
the presence of MF59 increased the amount of intracellular antigen. Similarly,
serological antibody titers to gD2 were 207-fold higher after two injections when
MF59 was administered with the antigen. These findings suggest that MF59
interacts with antigen presenting cells at the site of injection and then moves
to the draining lymph nodes, where it increases the efficiency of antigen
presentation to T cells.
PMID- 9637762
TI - Interaction between human interleukin-2-activated natural killer cells and heat
killed germ tube forms of Candida albicans.
AB - Human interleukin-2-activated natural killer (LAK) cells are able to recognize
and to bind to both live and heat-killed germ tube forms of Candida albicans,
establishing a wide and intimate contact as revealed by electron microscopic
observations. Following the interaction, LAK cells are activated: an increased
expression of some cytokine mRNA (in particular, TNF-alpha, GM-CSF, and IFN
gamma) has been revealed by RT-PCR and perforin secretion has been suggested by
immunofluorescence microscopy. Nonetheless, neither morphological damage or
growth inhibition of fungal target cells have been detected. Instead, evident
signs of cell damage could be noticed in interacting LAK cells. Moreover, the
observation by transmission electron microscopy of LAK cell-germ tube conjugates
revealed the presence of apoptotic cells. The analysis of LAK cell cytotoxic
activity against DAUDI cells showed that the lymphocytic effector underwent a
significant reduction in its lytic capability after the interaction with C.
albicans. The results obtained in this in vitro study seem to indicate that in
such an interaction LAK cells cannot directly inhibit or kill the fungal pathogen
by using their lytic machinery but they secrete those cytokines which have
stimulatory effects on phagocytic cells. The ultimate results are the programmed
death of LAK cells and the enhancement of the fungicidal activity exerted by
competent cells.
PMID- 9637763
TI - Interleukin-12 induces tyrosine phosphorylation of an 85-kDa protein associated
with the interleukin-12 receptor beta 1 subunit.
AB - Interleukin-12 (IL12) is a heterodimeric cytokine composed of p35 and p40
subunits and having multiple immunomodulatory effects on T cells as well as on
natural killer cells. Two subunits, beta 1 and beta 2, consisting of the
functional IL12 receptor complex, have been recently identified as members of the
hemopoietin receptor superfamily, bearing strong homology to gp130. In the
present study, we attempted to further characterize the biochemical nature of the
IL12 receptor complex and to delineate IL12-triggered signal transduction
pathways. To this end, we established a Jurkat transfectant (JIL12R beta 1t)
highly expressing the recombinant human IL12 receptor beta 1 subunit. Using this
transfectant, we identified an 85-kDa protein (p85) which is associated with the
beta 1 subunit and appears to be a cell surface protein, but is distinct from the
beta 2 subunit (130 kDa). p85 was also detected in PHA-activated T cells.
Importantly, p85 was rapidly tyrosine phosphorylated upon stimulation of both
JIL12R beta 1t cells and PHA-activated T cells with IL12. These results suggest
that p85 is a component of the IL12 receptor complex and may play a significant
role in mediating IL12-dependent signals.
PMID- 9637764
TI - Glucocorticoid receptors are differentially expressed in the cells and tissues of
the immune system.
AB - Cytosolic glucocorticoid receptor (GR) binding studies on immune tissues
demonstrate that the thymus exhibits three to four times higher levels of GR
protein than the spleen. High levels of GR are consistent with the exquisite
sensitivity of the thymus to glucocorticoid exposure. Nevertheless, whole cell
binding studies reveal similar levels of GR in immature thymic T lymphocytes and
more mature, splenic T lymphocytes. Moreover, whole cell binding techniques
indicate that neutrophils (which represent roughly 30% of splenic leukocytes)
exhibit higher GR than both T and B lymphocytes, further contradicting results
from cytosolic binding studies. To address these inconsistencies, GR protein was
assessed in immune cells and tissues using cytosolic radioligand binding. Western
blot analysis, and immunocytochemistry. Consistent with previous cytosolic
receptor binding studies on immune tissue homogenates, thymic T cells were found
to have higher levels of GR than T cells isolated from the spleen. In addition,
neutrophils were found to have fewer GR than lymphocytes and monocytes. These
results indicate a meaningful relationship between receptor expression and known
sensitivity to glucocorticoids.
PMID- 9637765
TI - Strength of signal through BCR determines the fate of cycling B cells by
regulating the expression of the Bcl-2 family of survival proteins.
AB - Cycling, splenic B cells were recultured with: (1) no stimulant to reflect poorly
competitive clones; (2) soluble, whole anti-mu to reflect clones that bind
soluble immune complexes; (3) soluble F(ab')2 anti-mu to reflect clones that bind
soluble antigen; and (4) immobilized anti-mu to reflect clones that bind antigen
presented by FDC. All four groups displayed similar levels of the death proteins
Bax and Bcl-xS. In contrast, cycling B cells restimulated with either soluble
F(ab')2 or immobilized anti-mu expressed heightened levels of the survival
protein Bcl-xL, and only cells restimulated with immobilized anti-mu expressed
the survival protein Bcl-2. Cycling B cells restimulated with either soluble
F(ab')2 or immobilized anti-mu displayed a selective survival advantage over
cycling B cells receiving no stimulus or soluble, whole anti-mu by both enhancing
their responsiveness to CD40 ligand, a Th-cell-derived signal, and increasing the
period that the cycling B cells remained responsive to this Th-cell-derived
signal. The Th-cell-derived signal did not appreciably alter cycling B cell
expression of Bcl-2 family members.
PMID- 9637766
TI - Human dendritic cells, pulsed with either melanoma tumor cell lysates or the
gp100 peptide(280-288), induce pairs of T-cell cultures with similar phenotype
and lytic activity.
AB - Dendritic cells (DCs) pulsed with unfractionated tumor cell lysates or defined
tumor peptides provide potent vaccines which elicit strong antitumor immunity. In
this study, we generated DCs from the 2-h adherent progenitor cells obtained from
the peripheral blood of melanoma patients. These DCs were able to capture
biotinylated melanoma tumor cell lysates. We examined the efficacy of immunogens
composed of DCs loaded either with the melanoma peptide gp100 [amino acids 280
288 (DC/gp100)] or with lysates from melanoma tumor cells (DC/lysates) in
inducing cytotoxic T-cells from autologous PBLs of HLA-A2 melanoma patients.
After four to five weekly stimulations of bulk PBLs with DC/gp100 or DC/lysates,
the cultures were enriched with CD3+ T-cells and exhibited one of three
phenotypic and functional patterns: (1) Predominant expression of CD8+ and MHC
class I-restricted CTLs which displayed strong lytic activity against melanoma
cells and T2 cells loaded with the gp100 peptide, (2) mixed CD4+/CD8+ phenotype
and weak lytic activity, or (3) nonlytic and predominantly CD4+ cultures.
Interestingly, T-cell cultures from each patient exhibited similar phenotypes and
lytic activities whether the stimulant was DC/gp100 or DC/cell lysates. Our study
demonstrates that DCs pulsed with soluble melanoma peptides or cell lysates are
capable of inducing CD8+ CTLs from autologous PBLs of some, but not all, melanoma
patients. The function and phenotype of the generated T-cell cultures are
governed by DCs since both antigens (the gp100 peptide and melanoma lysates),
when presented by a given DC preparation, induced similar T-cell cultures. In
summary, it may be difficult to predict the nature of the cellular responses
elicited by DC/tumor antigen vaccines from patient to patient.
PMID- 9637767
TI - Identification of a lectin that induces cell death in developing chicken B cells.
AB - The bursa of Fabricius is required for the development of a diverse B cell
repertoire in chickens. Bursal B cells are dependent on survival signals within
the bursa and their removal from the bursa results in death by apoptosis. To find
molecules that regulate B cell survival, a panel of mAb and lectins was screened
for the ability to either accelerate or prevent B cell death in culture. The
fucose-specific lectin Aleuria aurantia agglutinin (AAA) rapidly rendered B cells
permeable to propidium iodide. Incubation with the lectin also accelerated the
appearance of internucleosomal DNA fragmentation and nuclear condensation,
characteristics of apoptotic cell death. On Western blots the lectin detects a
single protein band of approximately 48-50 kDa molecular weight. AAA detects
fucose in an alpha 1-6 linkage and the restriction of this fucose linkage to a
single protein suggests that it may be functionally important in the regulation
of cell survival.
PMID- 9637769
TI - The LCC15-MB human breast cancer cell line expresses osteopontin and exhibits an
invasive and metastatic phenotype.
AB - We have characterized the LCC15-MB cell line which was recently derived from a
breast carcinoma metastasis resected from the femur of a 29-year-old woman. LCC15
MB cells are vimentin (VIM) positive, exhibit a stellate morphology in routine
cell culture, and form penetrating colonies when embedded in three-dimensional
gels of Matrigel or fibrillar collagen. They show high levels of activity in the
Boyden chamber chemomigration and chemoinvasion assays, and like other invasive
human breast cancer (HBC) cell lines, LCC15-MB cells activate matrix
metalloproteinase-2 in response to treatment with concanavalin A. In addition,
these cells are tumorigenic when implanted subcutaneously in nude mice and
recolonize bone after arterial injection. Interestingly, both the primary lesion
and the bone metastasis from which LCC15-MB were derived, as well as the
resultant cell line, abundantly express the bone matrix protein osteopontin
(OPN). OPN is also expressed by the highly metastatic MDA-MB-435 cells, but not
other invasive or noninvasive HBC cell lines. Expression of OPN is retained in
the subcutaneous xenograft and intraosseous metastases of LCC15-MB as detected by
immunohistochemistry. Both VIM and OPN expression have been associated with
breast cancer invasion and metastasis, and their expression by the LCC15-MB cell
line is consistent with its derivation from a highly aggressive breast cancer.
These cells provide a useful model for studying molecular mechanisms important
for breast cancer metastasis to bone and, in particular, the implication(s) of
OPN and VIM expression in this process.
PMID- 9637770
TI - Regulation of protrusion shape and adhesion to the substratum during chemotactic
responses of mammalian carcinoma cells.
AB - We report here the first direct observation of chemotaxis to EGF by rat mammary
carcinoma cells. When exposed to a gradient of EGF diffusing from a micropipette,
MTLn3 cells displayed typical ameboid chemotaxis, extending a lamellipod-like
protrusion and moving toward the pipette. Using a homogeneous upshift in EGF to
model stimulated lamellipod extension (J. E. Segall et al., 1996, Clin. Exp.
Metastasis 14, 61-72), we analyzed the relationship between adhesion and
chemoattractant-stimulated protrusion. Exposure to EGF led to a rapid remodeling
of the adhesive contacts on adherent cells, in synchrony with extension of a flat
lamellipod over the substratum. EGF-stimulated lamellipods still extended in the
presence of adhesion-blocking peptides or over nonadhesive surfaces. They were,
however, slightly shorter and retracted rapidly under those conditions. The major
protrusive structure observed on well-spread, adherent cells, after EGF
stimulation was a flat broad lamellipod, whether or not in contact with the
substratum, while cells in suspension showed transient protrusive activity over
the entire cell surface. We conclude that the initial adhesive status of the cell
conditions the shape of the outcoming protrusion. Altogether our results suggest
that, although adhesive contacts are not necessary for lamellipod extension, they
play a role in stabilizing the protrusion as well as in the control of its final
shape and amplitude.
PMID- 9637771
TI - The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear
distribution of SR proteins and influence pre-mRNA splicing.
AB - The three members of the Clk family of kinases (Clk1, 2, and 3) have been shown
to undergo conserved alternative splicing to generate catalytically active (Clk)
and inactive (ClkT) isoforms. The prototype, murine Clk1 (mClk1), is a nuclear
dual-specificity kinase that can interact with, and cause the nuclear
redistribution of, SR proteins. In this study, we demonstrate that the human Clk2
and Clk3 (hClk2 and 3) are also found within the nucleus and display dual
specificity kinase activity. The truncated isoforms, hClk2(T) and hClk3(T),
colocalize with SR proteins in nuclear speckles. We also show catalytically
active hClk2 and hClk3 cause the redistribution of SR proteins and can regulate
the alternative splicing of a model precursor mRNA substrate in vivo.
PMID- 9637772
TI - Cytochemical detection of a senescence-associated beta-galactosidase in
endothelial and smooth muscle cells from human and rabbit blood vessels.
AB - A beta-galactosidase activity has recently been used as a histochemical marker of
replicative senescence in human fibroblasts and keratinocytes. To establish
whether this marker could be used to detect senescence of vascular cells, we have
investigated its presence in cultures of serially passaged human umbilical vein
endothelial cells and rabbit aortic smooth muscle cells. beta-Galactosidase
activity was detected by light microscopy using the chromogenic substrate 5-bromo
4-chloro-3-indolyl beta-d-galactopyranoside. In endothelial cell cultures,
lysosomal beta-galactosidase activity, which is detected at pH 4.0, was present
in all cells regardless of their replicative age. In contrast, senescence
associated beta-galactosidase activity, which is detected at pH 6.0, was absent
in the majority of cells in early passage cultures (<15 cumulative population
doublings), but was present in a large proportion of cells (up to 62%) in late
passage cultures (>30 cumulative population doublings); in intermediate passage
cultures (15-30 cumulative population doublings) it was found in fewer than 15%
of the cells. The increase in the percentage of senescence-associated beta
galactosidase-positive cells correlated with a decrease in the cell density at
confluence and with a marked increase in cell size. Counterstaining with an
antibody directed against the endothelial cell marker CD31 showed that senescent
cells retained the expression of this antigen. Senescence-associated beta
galactosidase was also detected in serially passaged, but not in primary explant
cultures of rabbit aortic vascular smooth muscle cells. The presence of
senescence-associated beta-galactosidase in cultured vascular smooth muscle cells
and endothelial cells suggests that this marker could be used to study the role
of cellular senescence in vascular disease.
PMID- 9637773
TI - Age changes in stem cells of murine small intestinal crypts.
AB - Cell senescence is seen in many types of differentiated cells but age changes in
stem cells have not previously been clearly demonstrated. Changes in stem cells
may be of great importance for the ageing process, because any decline with age
in the numbers and functional integrity of stem cells can lead to progressive
deterioration of function and of proliferative homeostasis in tissues. Stem cells
of the murine small intestine provide an excellent model system because these
cells occupy a well-defined position near the base of the crypts of Lieberkuhn.
We examined mice aged between 5 and 32 months and found age-related alterations
in the histology of the small intestine and in the apoptotic response of stem
cells to low-dose irradiation. Apoptosis in the crypts is concentrated around the
stem cell position and can be markedly elevated by exposure to radiation or
cytotoxic agents, suggesting that "suicide" of damaged stem cells may be an
important system for long-term tissue maintenance. Animals aged 5, 15, 18, and 29
months were exposed to either 1 or 8 Gy gamma irradiation. A twofold increase in
the level of apoptosis was seen following 1 Gy gamma irradiation in the 29-month
old animals, compared to the young and middle-age groups. After 8 Gy irradiation
the level of apoptosis in all age groups was high and the age effect less
pronounced. The data suggest that stem cells do undergo some functional
alteration with age.
PMID- 9637774
TI - Hypophosphorylation of the RB protein in S and G2 as well as G1 during growth
arrest.
AB - The RB tumor suppressor protein is a cell cycle regulator, where
hypophosphorylated RB is associated with G1/0 arrest and its cyclin-dependent
phosphorylation in G1 allows progression from G1 to S. The present report shows
that in human leukemia cells induced to undergo growth arrest with sodium
butyrate or DMSO, hypophosphorylation of the RB protein is not G1 restricted and
also occurs in S and G2/M cells as well as in G1 cells when growth is inhibited.
While all of the RB protein in G1/0 cells is hypophosphorylated, residual cells
in S and G2 have significant detectable amounts of hypophosphorylated RB as well
as still hyperphosphorylated RB protein. Thus RB hypophosphorylation can be
induced in S and G2 as well as the G1 phase. The results show that growth
retardation in other than the G1 phase is associated with occurrence of
hypophosphorylated RB. RB may thus have a broader capability to inhibit
proliferation than just in G1.
PMID- 9637775
TI - Characterization of topotecan-mediated redistribution of DNA topoisomerase I by
digital imaging microscopy.
AB - Topographical image measures have been used to characterize the subnuclear
distribution of DNA topoisomerase I in human tumor cell lines. This topographical
analysis allowed a mathematical description of staining patterns to be produced
that did not depend on subjective grading. The redistribution of topoisomerase I
in response to increasing concentrations of topotecan was then monitored by this
method. The cell lines were stained for topoisomerase I by indirect
immunofluorescence methods. Digital imaging microscopy and image analysis were
used to extract the nucleus from each cell, and nine parameters describing the
topography of the distribution of topoisomerase I within the nucleus were
computed for each. Use of multivariate analysis of variance enabled this nine
parameter set to be reduced to a single canonical variable, representing 60-90%
of the observed internuclear variance. Plotting the canonical variable vs drug
concentration resulted in dose-response curves that could be fitted well by a
simple Emax model. From these curve fits, EC50 and Emax values for drug-induced
redistribution of topoisomerase I were determined. Our results indicate that
neither the maximum extent of topoisomerase I redistribution (Emax) nor the EC50
for drug-induced redistribution correlated well with the growth inhibition
produced by continuous exposure to topotecan in these cell lines. However, the
EC50 determined for the 1-h high-concentration exposure did reflect the growth
inhibition produced in cells exposed to the drug for 1 h. The methodology
described may also be generally applied to any antigen of interest.
PMID- 9637776
TI - Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at
late G1 and S phase.
AB - We have previously reported that certain tyrphostins which block EGF-R
phosphorylation in cell-free systems fail to do so in intact cells. Nevertheless,
we found that this family of tyrphostins inhibits both EGF- and calf serum
induced cell growth and DNA synthesis [Osherov, N.A., Gazit, C., Gilon, and
Levitzki, A. (1993). Selective inhibition of the EGF and HER2/Neu receptors by
Tyrphostins. J. Biol. Chem. 268, 11134-11142.] Now we show that these tyrphostins
exert their inhibitory activity even when added at a time when the cells have
already passed their restriction point and receptor activation is no longer
necessary. AG555 and AG556 arrest 85% of the cells at late G1, whereas AG490 and
AG494 cause cells to arrest at late G1 and during S phase. No arrest occurs
during G2 or M phase. Further analysis revealed that these tyrphostins act by
inhibiting the activation of the enzyme Cdk2 without affecting its levels or its
intrinsic kinase activity. Furthermore, they do not alter the association of Cdk2
to cyclin E or cyclin A or to the inhibitory proteins p21 and p27. These
compounds also have no effect on the activating phosphorylation of Cdk2 by Cdk2
activating kinase (CAK) and no effect on the catalytic domain of cdc25
phosphatase. These compounds lead to the accumulation of phosphorylated Cdk2 on
tyrosine 15 which is most probably the cause for its inhibition leading to cell
cycle arrest at G1/S. A structure-activity relationship study defines a very
precise pharmacophore, suggesting a unique molecular target not yet identified
and which is most probably involved in the regulation of the tyrosine
phosphorylated state of Cdk2. These compounds represent a new class of cell
proliferation blockers whose target is Cdk2 activation.
PMID- 9637777
TI - Increased rate of HIV-1 entry and its cytopathic effect in CD4+/CXCR4+ T cells
expressing relatively high levels of CD26.
AB - The role of the T-cell activation antigen CD26 was evaluated in viral entry and
infection of CD4(+)/CXCR4(+) cells by the lymphotropic HIV-1 Lai isolate. For
this purpose, CEM T cells, which are permissive to HIV infection and express low
levels of CD26, were used to establish by transfection four groups of cell clones
expressing either low, high, and very high levels of CD26, or expressing the anti
sense RNA of CD26. Entry was monitored by the detection of proviral DNA synthesis
and the kinetics of virus production, whereas the cytopathic effect was
demonstrated by the occurrence of apoptosis. HIV entry and infection were
consistently accelerated by at least 24 to 48 h in clones expressing high levels
of CD26 compared to the parental cells or to the clones expressing low levels of
CD26. Interestingly, infection of clones expressing very high levels of CD26 was
not accelerated and showed a kinetics of infection similar to that of low CD26
expressing clones. Moreover, HIV infection was significantly reduced in the
clones expressing CD26 anti-sense RNA. In the different clones, apoptosis was
dependent on the severity of virus infection and occurred after the accumulation
of HIV envelope glycoproteins. Our results demonstrate that with equivalently
expressed levels of CD4 and CXCR4 in cell lines established from CEM cells,
relatively high levels of CD26 contribute to an increased rate of HIV entry,
infection, and apoptosis. Furthermore, they point out that overexpression of CD26
in a given cell line may lead to a negative effect on HIV infection.
Consequently, CD26 appears to regulate HIV entry and apoptosis, processes which
are critical for viral pathogenesis.
PMID- 9637778
TI - PKN interacts with a paraneoplastic cerebellar degeneration-associated antigen,
which is a potential transcription factor.
AB - PKN is a fatty acid-activated serine/threonine protein kinase, having a catalytic
domain homologous to protein kinase C family. PKN has been recently reported to
interact with a small GTP-binding protein Rho and cytoskeletal proteins such as
neurofilament and alpha-actinin. To identify the new components of the PKN
signaling pathway, the yeast two-hybrid system was employed. Using the amino
terminal regulatory domain of PKN as a bait, cDNA encoding a neural antigen
PCD17, which is recognized by characteristic antibodies of patients with
paraneoplastic cerebellar degeneration, was isolated from a human brain cDNA
library. The interaction between PKN and PCD17 was also determined by the in
vitro binding analysis. PCD17 was coimmunoprecipitated with PKN from the lysate
of COS7 cells transfected with both expression constructs for PKN and the amino
terminal region of PCD17. PCD17 was phosphorylated by PKN, and the extent of this
phosphorylation was enhanced by addition of 40 microM arachidonic acid. The amino
terminal region of PCD17 could form a homodimer in vitro, and PCD17 fused to the
Gal4 DNA binding domain showed the transcriptional transactivation of the
chloramphenicol acetyltransferase reporter gene linked to 5 Gal4 binding sites
and minimal promoter in rat C6 glioma cells. These results suggest the
participation of PCD17 in gene expression and lead to a clue for elucidating the
PKN signaling pathway from the cytosol to the nucleus.
PMID- 9637779
TI - Apoptotic changes preceding necrosis in lipopolysaccharide-treated macrophages in
the presence of cycloheximide.
AB - Apoptotic changes occurred specifically in a macrophage-like cell line, J774.1,
treated with lipopolysaccharide (LPS) and cycloheximide (CHX) prior to the
release of lactate dehydrogenase (LDH). The addition of 100 ng/ml LPS and 10
microg/ml CHX induced both the formation of DNA nicks and elevation of caspase-3
like activity (DEVDase) after 75 min, and then the cleavage of poly(ADP-ribose)
polymerase (PARP) into 28-kDa fragments, formation of apoptotic bodies, and DNA
ladder formation. These apoptotic changes were reversible until 60 min, however,
later than 75 min after LPS and CHX addition, the apoptosis proceeded normally
even on extensive washing of the macrophages, which removed the LPS and CHX.
These results suggest that there is a "point of no return" in the apoptotic
processes in macrophages induced by LPS and CHX and that DNA nicks and activation
of DEVDase are critical for these processes.
PMID- 9637780
TI - Mitochondrial membrane potential and DNA stainability in human sperm cells: a
flow cytometry analysis with implications for male infertility.
AB - Sperm cells from control donors of proven fertility and men from barren couples
were studied by conventional procedures, i.e., light microscopy as well as flow
cytometry. Light microscopy analysis of semen included the measurement of
spermatozoa concentration, morphology, and motility. All the men from barren
couples were asthenozoospermic at the conventional analysis of semen samples.
Flow cytometry was applied to study two important parameters of sperm cells:
mitochondrial membrane potential (MMP) assessed by the cationic dye JC-1 and DNA
stainability with propidium iodide (PI). JC-1 staining was more reliable than the
classical procedure used for this purpose, i.e., rhodamine 123 (Rh123) staining,
and allowed us to show a positive correlation between MMP and spermatozoa
motility. Regarding DNA analysis, a higher relative percentage of immature
spermatozoa, showing a high accessibility of DNA to the intercalating PI
fluorochrome, was found in men from barren couples compared to donors of proven
fertility. The relative percentage of immature spermatozoa was significantly
higher in semen from oligoasthenozoospermic subjects. Moreover, a positive
correlation was found between immature spermatozoa, as evaluated by PI staining,
and cells with depolarized mitochondria, as evaluated by JC-1 staining,
suggesting that spermatozoa defective for nuclear maturity could be functionally
defective cells. No correlation between immature spermatozoa determined by FCM
and immature spermatozoa determined by light microscopy was found, suggesting
that these two techniques assess sperm cell maturity at different levels.
PMID- 9637781
TI - The human myoepithelial cell exerts antiproliferative effects on breast carcinoma
cells characterized by p21WAF1/CIP1 induction, G2/M arrest, and apoptosis.
AB - Ductal carcinoma in situ of the breast (DCIS) is surrounded by a layer of
myoepithelial cells. Our previous studies have suggested that these myoepithelial
cells exert paracrine tumor-suppressive effects on invasion of breast carcinoma
cells. Conditioned medium (CM), concentrated 10-100x of HMS-1, HMS-3, and HMS-4,
human myoepithelial cell lines, block Matrigel invasion of a series of carcinoma
cell lines. Immunoprecipitation of maspin, a recently described serpin, from
these CM abolishes this anti-invasive effect. Both CM and maspin
immunoprecipitated CM, however, exert equal antiproliferative effects on a series
of ER+ and ER- cell lines including MCF-7, T47D, MDA-MB-231, and MDA-MB-468.
These antiproliferative effects are characterized by induction of a G2/M arrest,
a twofold increase in p21(WAF1/CIP1) transcription and expression, and a
threefold increase in apoptosis in the breast carcinoma lines examined. The
antiproliferative effects mediated by myoepithelial cell CM do not manifest
themselves in an autocrine manner, are not mediated by TGF-beta1, nor involve ER-
or p53-dependent pathways. Neither the antiproliferative nor the anti-invasive
effects of myoepithelial cell CM is observed with nonmyoepithelial cell CM. The
in vitro observations of our present study may have relevance in explaining the
increased degree of apoptosis exhibited by DCIS cells in vivo. Our findings
illustrate another way myoepithelial cells function as natural paracrine tumor
suppressors.
PMID- 9637782
TI - The expression of heat shock protein 70 decreases with cellular senescence in
vitro and in cells derived from young and old human subjects.
AB - Because heat shock proteins have been shown to play a critical role in protecting
cells from hyperthermia and other types of stresses, it was of interest to
determine what effect cellular senescence in vitro and cells cultured in vitro
from young and old human donors have on the ability of cells to regulate the
expression of heat shock protein 70 (hsp70), the most prominent and most
evolutionary conserved of the heat shock proteins. The ability of early and late
passage IMR-90 lung fibroblasts and epidermal melanocytes and skin fibroblasts
obtained from young and old human donors to express hsp70 was determined after a
brief heat shock. We found that the levels of hsp70 protein and mRNA were lower
in late passage cells and cells from old donors than in early passage cells and
cells from young donors. The binding activity of the heat shock transcription
factor HSF1, as measured by a gel shift assay, was significantly higher in early
passage cells and cells from young donors in comparison to late passage cells and
cells from old donors. In addition, the levels of HSF1 decreased significantly in
late passage cells and cells from old donors in comparison to early passage cells
and cells from young donors. Thus, our study demonstrates that the induction of
hsp70 by hyperthermia in fibroblasts is significantly lower in late passage
fibroblasts and in fibroblasts from old donors. In addition, our study shows that
the decline in hsp70 expression during cellular senescence in vitro and in cells
derived from old human subjects is paralleled by a decrease in the levels of
HSF1.
PMID- 9637783
TI - Regulation of vascular endothelial growth factor receptor-2 (Flk-1) expression in
vascular endothelial cells.
AB - We have previously reported the existence of a synergistic interaction between
vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
(bFGF) in the induction of angiogenesis in vitro. Here we demonstrate that bFGF
increases VEGF receptor-2 (VEGFR-2/Flk-1) expression: mRNA levels were increased
by 4.5- to 8.0-fold and total protein by 2.0- to 3.5-fold, in bovine
microvascular endothelial (BME), aortic endothelial (BAE), and transformed fetal
aortic (GM7373) endothelial cells. VEGF itself did not affect VEGFR-2 expression,
and neither bFGF nor VEGF altered expression of FGF receptor-1. We also show that
synergism occurs at the level of proliferation when this is measured in a three
dimensional but not in a conventional two-dimensional assay. Differences in the
level of VEGFR-2 expression were also observed when cells were grown on or within
collagen gels under different conditions: mRNA levels were lowest under sparse
conditions, increased 20- to 26-fold at confluence, and increased even further
(57-fold) when cells were cultured in suspension in three-dimensional collagen
gels. Finally, a synergistic increase was seen in the level of expression of
urokinase and urokinase receptor mRNAs when cells were exposed to bFGF and VEGF
for 4 days. These findings demonstrate that the level of VEGFR-2 expression can
be modulated by environmental factors including cytokines and the geometry of the
culture conditions and provide some insight into the mechanisms of synergism
between bFGF and VEGF in the induction of angiogenesis in vitro.
PMID- 9637784
TI - PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the
induction of apoptosis and reverses Bcl-2-mediated cytoprotection.
AB - One critical step of the apoptotic process is the opening of the mitochondrial
permeability transition (PT) pore leading to the disruption of mitochondrial
membrane integrity and to the dissipation of the inner transmembrane proton
gradient (Delta Psim). The mitochondrial PT pore is a polyprotein structure which
is inhibited by the apoptosis-inhibitory oncoprotein Bcl-2 and which is closely
associated with the mitochondrial benzodiazepine receptor (mBzR). Here we show
that PK11195, a prototypic ligand of the 18-kDa mBzR, facilitates the induction
of Delta Psim disruption and subsequent apoptosis by a number of different
agents,including agonists of the glucocorticoid receptor,chemotherapeutic agents
(etoposide, doxorubicin),gamma irradiation, and the proapoptotic second messenger
ceramide. Whereas PK11195 itself has no cytotoxic effect, it enhances apoptosis
induction by these agents. This effect is not observed for benzodiazepine
diazepam, whose binding site in the mBzR differs from PK11195. PK11195 partially
reverses Bcl-2 mediated inhibition of apoptosis in two different cell lines.
Thus, transfection-enforced Bcl-2 overexpression confers protection against
glucocorticoids and chemotherapeutic agents, and this protection is largely
reversed by the addition of PK11195. This effect is observed at the level of
Delta Psim dissipation as well as at the level of nuclear apoptosis. To gain
insights into the site of action of PK11195, we performed experiments on isolated
organelles. PK11195 reverses the Bcl-2-mediated mitochondrial retention of
apoptogenic factors which cause isolated nuclei to undergo apoptosis in a cell
free system. Mitochondria from control cells, but not mitochondria from Bcl-2
overexpressing cells, readily release such apoptogenic factors in response to
atractyloside, a ligand of the adenine nucleotide translocator. However, control
and Bcl-2-overexpressing mitochondria respond equally well to a combination of
atractyloside and PK11195. Altogether, these findings indicate that PK11195
abolishes apoptosis inhibition by Bcl-2 via a direct effect on mitochondria.
Moreover, they suggest a novel strategy for enhancing the susceptibility of cells
to apoptosis induction and, concomitantly, for reversing Bcl-2-mediated
cytoprotection.
PMID- 9637785
TI - The regulation of cyclin D1 expression in senescent human fibroblasts.
AB - To clarify the molecular mechanisms of cyclin D1 expression during in vitro
cellular aging, we investigated the binding of nuclear protein factors to the
cyclin D1 gene promoter domain in young and senescent normal human fibroblasts.
The cyclin D1 promoter binding activities of nuclear protein factors from young
and senescent cells were examined by the gel mobility shift assay. Our findings
revealed that (i) the binding of a specific nuclear factor to the enhancer
element was very weak in senescent cells; (ii) the binding of a specific nuclear
factor to the CRE, which is independent of cell growth, was unchanged between
young and senescent cells; (iii) nuclear factors from senescent cells did not
bind to the presumptive silencer element; (iv) the binding of specific factors to
the Inr (transcription initiation region) and E2F increased with growth
stimulation in young cells and was weakly detectable in senescent cells; and (v)
the binding of Sp1 to its promoter element occurred only in senescent cells. The
analysis of the silencer element by the gel mobility shift assay revealed that
the essential sequence required for binding of specific factors to the silencer
element was TTTAAT. The molecular weight of the binding factor to the silencer
element was determined to be approximately 35 kDa by the Southwestern blotting
and UV cross-linking assay. Thus, we postulated that the observed increase of
cyclin D1 expression during cellular aging is due to an increase in the binding
activity of specific nuclear protein factors to an enhancer element, Sp1, and a
decrease in binding to a silencer element in senescent cells.
PMID- 9637786
TI - Phenobarbital suppresses growth and accelerates restoration of differentiation
markers of primary culture rat hepatocytes in the chemically defined hepatocyte
growth medium containing hepatocyte growth factor and epidermal growth factor.
AB - Phenobarbital (PB), a liver-tumor promoter, at a concentration of 3 mM
dramatically inhibited the growth of adult rat hepatocytes in the chemically
defined medium, HGM, with added hepatocyte growth factor (HGF) and epidermal
growth factor (EGF). In concurrence with these findings, PB down-regulated
expression of the HGF receptor (c-met) and suppressed production of the autocrine
growth factor transforming growth factor-alpha (TGF-alpha). Furthermore, PB down
regulated expression of transcription factors associated with proliferation such
as AP1 and NF-kappaB. In the presence of PB, hepatocytes remained morphologically
differentiated and restoration of the expression of mature hepatocyte markers,
such as albumin and cytochrome P450s (1A, 2B1/2, and 2E1), was accelerated after
an initial phase of growth. Additionally, PB strongly suppressed expression of
the mRNA for alpha-fetoprotein, a protein primarily expressed by fetal liver, and
the accelerative effect of PB on restoration of mature hepatocyte markers showed
a correlation with the up-regulation of the hepatocyte-enriched transcription
factors HNF3 and HNF4. When the effects of PB on various extracellular matrix
proteins were examined, the data indicated that PB specifically suppressed
laminin and fibronectin production by hepatocytes, suggesting an important role
for these proteins in growing hepatocyte cultures.
PMID- 9637787
TI - Nucleotide excision repair is not required for the antiapoptotic function of
insulin-like growth factor 1.
AB - The expression of ERCC1, a member of the nucleotide excision repair (NER) family,
is enhanced in cells transfected with insulin-like growth factor 1 (IGF-1)
receptors. Of interest, an excellent concordance between ERCC1 expression and NER
mediated cell survival has been demonstrated. The two aims of the present study
were to determine the signaling pathways used by IGF-1 to confer protection
against apoptotic cell death in Chinese hamster ovary (CHO) cells and to assess
the role of NER in this IGF-1 action. Experiments with pharmacological inhibitors
indicated that phosphatidylinositol 3-kinase (PI 3-kinase) but not mitogen
activated protein kinase (ERK1/ERK2) mediates IGF-1 antiapoptotic activity. Using
two series of CHO cells that have altered expression of ERCC1 or XPB/ERCC3, we
examined IGF-1's ability to delay apoptotic death and reduction of mitochondrial
oxidative function mediated by growth factor withdrawal. IGF-1 effectively
blocked apoptosis, concomitant with increased MTT activity, in a pair of CHO cell
lines expressing inactive ERCC1 (43-3B cells) and the transfected line of the
mutant carrying the expressed human ERCC1 gene (83-G5 cells). Similarly, repair
deficient UV24 cells, which lack XPB/ERCC3, and their parental line AA8 were also
responsive to the IGF-1's antiapoptotic capacity. In the presence of IGF-1, these
cell lines became resistant to the cleavage of poly(ADP-ribose) polymerase, a key
player in DNA damage recognition and DNA repair. These results suggest that PI 3
kinase activation plays a determinant role in the antiapoptotic function of IGF
1, but that functional NER does not play a critical part in mediating this IGF-1
response.
PMID- 9637788
TI - Adjacent carboxyterminal tyrosine phosphorylation events identify functionally
distinct ErbB2 receptor subsets: implications for molecular diagnostics.
AB - Site-directed mutagenesis can define the effects of altering one or more amino
acids within a protein, but this technique may lack sensitivity when used to
characterize proteins which differ conformationally or posttranslationally at
multiple sites. A novel alternative approach involves the direct characterization
of wild-type protein isoforms identified by site-specific immunodetection. To
this end we have developed antibodies which recognize ErbB2 subsets characterized
by adjacent tyrosine phosphorylation events (Y1222 and Y1248) in the C-terminal
tail of the oncoprotein. Here we use these phosphoantibodies to demonstrate the
existence of tyrosine-phosphorylated ErbB2 subsets which differ in their patterns
of heterooligomer formation, in vitro autophosphorylation, and recruitment of SH2
containing substrates. Furthermore, Y1222 and/or Y1248 phosphoantibody
immunoreactivity is readily detectable in ErbB2-overexpressing human breast
tumors, in which context these phosphorylation events exhibit significant
discordance. These data confirm the value of site-specific immunodetection as a
strategy for characterizing phosphoprotein function in vitro and in vivo and
suggest that multisite phosphotyping of human tumors may contribute novel
clinicopathologic insights into the significance of the ErbB2 overexpression
phenotype.
PMID- 9637789
TI - In vivo effects of hepatocyte growth factor/scatter factor on mouse mammary gland
development.
AB - We have recently demonstrated the regulated expression of HGF/SF and its receptor
(c-met) during mouse mammary gland development together with the mitogenic,
motogenic and morphogenic effects of exogenous HGF/SF on primary mammary
epithelial cells in culture. This study was undertaken to analyze the influence
of HGF/SF on reconstituted mouse mammary gland development in vivo. Here we
report that overexpression of HGF/SF induces a range of alterations in the
architecture of virgin mouse mammary gland. These include an enhancement of
ductal end bud (mammary gland morphoregulatory control point) size and numbers
and hyperplastic branching morphogenesis. These data are the first demonstration
of the effects of HGF/SF on mammary epithelium in vivo.
PMID- 9637791
TI - A severely affected male born into a Rett syndrome kindred supports X-linked
inheritance and allows extension of the exclusion map.
PMID- 9637792
TI - The Environmental Genome Project: functional analysis of polymorphisms.
AB - The ultimate goal of the Environmental Genome Project is the improvement of human
health on the basis of information about the variations in certain genes. The
first phase of the project will involve the selection of the human genes and
characterization of the alleles occurring in the American population. However,
intelligent use of this information will require analysis of the relevance of the
allelic differences. Epidemiology alone will not solve the problem, and
mechanistic studies will be required. Factors to be considered in the design of
functional analyses are considered in this commentary.
PMID- 9637793
TI - A case of a laboratory animal feed with high estrogenic activity and its impact
on in vivo responses to exogenously administered estrogens.
AB - We recently noted that immature rats failed to exhibit a normal uterine response
to exogenously administered estradiol as assessed by both biochemical (induction
of gene expression) and morphological (altered uterine and vaginal histology and
size) end points. An initial analysis suggested that this was due to a high
degree of estrogenization from a dietary source which was producing a near
maximal uterotrophic response prior to hormone treatment. Subsequent chemical
analysis indicated that the feed in question contained high amounts of two well
known phytoestrogens, genistein (210 mg/kg) and daidzen (14 mg/kg), and the lot
of feed in question produced a large uterotrophic effect when fed to immature
ovariectomized rats. These findings illustrate that, despite increased awareness
of phytoestrogens, some batches of animal feed contain very high amounts of
estrogenic components which have marked effects on in vivo end points of hormone
action. These observations have important implications for both basic research
and screening methods that utilize in vivo approaches.
PMID- 9637795
TI - A specific spectrum of p53 mutations in lung cancer from smokers: review of
mutations compiled in the IARC p53 database.
AB - Mutations in the p53 gene are common in lung cancer. Using data from the the
International Agency for Research on Cancer p53 mutation database (R1), we have
analyzed the distribution and nature of p53 mutations in 876 lung tumors
described in the literature. These analyses confirm that G to T transitions are
the predominant type of p53 mutation in lung cancer from smokers. The most
frequently mutated codons include 157, 158, 179, 248, 249, and 273, and several
of them (157, 248, and 273) have been shown to correspond to sites of in vitro
DNA adduct formation by metabolites of polycyclic aromatic hydrocarbons (PAHs)
such as benzo(a)pyrene. Furthermore, most of the base changes at codons 248, 249,
and 273 in lung cancer differ from those commonly observed at these codons in
other cancers reported in the database. Thus, lung cancer from smokers shows a
distinct, unique p53 mutation spectrum that is not observed in lung cancer from
nonsmokers. These results further strengthen the association between active
smoking, exposure to PAHs, and lung cancer. They also indicate that a different
pattern of mutations occurs in nonsmokers, and this observation may help to
identify other agents causally involved in lung cancer in nonsmokers.
PMID- 9637794
TI - Oxidative stress in toxicology: established mammalian and emerging piscine model
systems.
AB - Interest in the toxicological aspects of oxidative stress has grown in recent
years, and research has become increasingly focused on the mechanistic aspects of
oxidative damage and cellular responses in biological systems. Toxic consequences
of oxidative stress at the subcellular level include lipid peroxidation and
oxidative damage to DNA and proteins. These effects are often used as end points
in the study of oxidative stress. Typically, mammalian species have been used as
models to study oxidative stress and to elucidate the mechanisms underlying
cellular damage and response, largely because of the interest in human health
issues surrounding oxidative stress. However, it is becoming apparent that
oxidative stress also affects aquatic organisms exposed to environmental
pollutants. Research in fish has demonstrated that mammalian and piscine systems
exhibit similar toxicological and adaptive responses to oxidative stress. This
suggests that piscine models, in addition to traditional mammalian models, may be
useful for further understanding the mechanisms underlying the oxidative stress
response.
PMID- 9637796
TI - A physiologically based pharmacokinetic model for 2,4-toluenediamine leached from
polyurethane foam-covered breast implants.
AB - Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low
dose exposure of patients to the carcinogen 2, 4-toluenediamine (2,4-TDA)
released from the degradation of the polyester urethane foam (PU) used in Meme
silicone breast implants. The tissues are represented as five compartments:
liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and
richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma
and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino
toluene) in rats given low doses of 2, 4-TDA intravenously and subcutaneously.
The rat model was extrapolated to simulate oral and implant routes in rats. After
adjusting for human physiological parameters, the model was then used to predict
the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane
foam implant found in a patient who weighed 58 kg with the Meme and had the
breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was
performed and the polyester urethane foam did present an unreasonable risk to
health for the patient.
PMID- 9637797
TI - A morbidity study of former pentachlorophenol-production workers.
AB - Pentachlorophenol (PCP) is a pesticide that was once widely used for wood
preservation. Commercial PCP contained impurities including higher chlorinated
dibenzo-p-dioxins (CDDs) and chlorinated dibenzofurans (CDFs). We investigated
the effects of occupational exposure to PCP and its CDD and CDF contaminants on
the skin, liver, porphyrin metabolism, and central and peripheral nervous
systems. In 1986 we conducted a medical survey of 366 workers who had been
engaged in the production of PCP at a single plant between 1938 and 1978. The
referent group consisted of 303 workers from the same plant who were not exposed
to these or related compounds. Exposure was determined from computerized
personnel records. The medical survey included an administered questionnaire,
medical record review, physical examination by dermatologists, internists, and
neurologists, and analysis of 24-hr urine for quantitative porphyrins among other
tests. In this paper we present the results of analyses of the general health,
chloracne, and porphyrin metabolism end points. The general health status of PCP
workers was similar to unexposed workers, but 17.8% of PCP workers had evidence
of current or past chloracne. PCP workers with chloracne had significantly higher
mean urinary excretion of coproporphyrins (117. 0 vs. 90.6 microg/24 hr) than
unexposed workers after controlling for potential confounders. Workers with
chloracne who had worked with both PCP and polychlorinated biphenyls had
significantly higher mean urinary excretions of hepta-, penta-, and
coproporphyrins than unexposed workers. We conclude that occupational exposure to
PCP is associated with chloracne and biochemical abnormalities which may persist
years after exposure.
PMID- 9637798
TI - Microcystic cyanobacteria causes mitochondrial membrane potential alteration and
reactive oxygen species formation in primary cultured rat hepatocytes.
AB - Cyanobacteria contamination of water has become a growing public health problem
worldwide. Microcystis aeruginosa is one of the most common toxic cyanobacteria.
It is capable of producing microcystins, a group of cyclic heptapeptide compounds
with potent hepatotoxicity and tumor promotion activity. The present study
investigated the effect of microcystic cyanobacteria on primary cultured rat
hepatocytes by examining mitochondrial membrane potential (MMP) changes and
intracellular reactive oxygen species (ROS) formation in cells treated with
lyophilized freshwater microcystic cyanobacteria extract (MCE). Rhodamine 123 (Rh
123) was used as a fluorescent probe for changes in mitochondrial fluorescence
intensity. The mitochondrial Rh-123 fluorescence intensity in MCE-treated
hepatocytes, examined using a laser confocal microscope, responded in a dose- and
time-dependent manner. The results thus indicate that the alteration of MMP might
be an important event in the hepatotoxicity caused by cyanobacteria. Moreover,
the parallel increase of ROS formation detected using another fluorescent probe,
2',7'-dichlorofluorescin diacetate also suggests the involvement of oxidative
stress in the hepatotoxicity caused by cyanobacteria. The fact that MMP changes
precede other cytotoxic parameters such as nuclear staining by propidium iodide
and cell morphological changes suggests that mitochondrial damage is closely
associated with MCE-induced cell injury in cultured rat hepatocytes.
PMID- 9637799
TI - Factors associated with self-reported, pesticide-related visits to health care
providers in the agricultural health study.
AB - To investigate factors associated with pesticide-related visits to health care
providers (i.e., doctor or hospital visits), responses to self-administered
questionnaires received from 35,879 licensed restricted-use pesticide applicators
participating in the Agricultural Health Study were analyzed. (In Iowa,
applicators are actually certified, whereas in North Carolina they are licensed;
for ease of reference, the term license will be used for both states in this
paper.) The cohort reported a total of more than 10.9 million pesticide
application days. These applications were associated with one or more pesticide
related health care visits by 2,214 applicators (7.0% of the applicator cohort
for whom health care visit data were available). The odds of a pesticide-related
health care visit were increased for commercial applicators compared to private
applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and
for applicators who used insecticides 70 times or more in their lifetime compared
to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After
adjusting for the number of applications in a logistic regression model,
significantly higher odds of health care visits were observed among North
Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52),
among applicators who mixed their own pesticides (OR = 1.65; CI, 1. 22-2.23), and
among applicators who personally repaired their pesticide application equipment
at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were
found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among
applicators who graduated from high school versus those who did not (OR = 0.82;
CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those
with at least some college). Several methods of pesticide application to crops,
seed, or stored grain were also associated with significantly elevated odds
ratios of health care visits. These observations suggest that several steps can
be taken to reduce the number of health care visits resulting from occupational
exposure to pesticides. The implications of this pattern of pesticide-related
health care visits may have etiologic implications for cancer and other chronic
diseases.
PMID- 9637801
TI - Toxic tides.
PMID- 9637800
TI - Aromatic hydrocarbon receptor polymorphism: development of new methods to
correlate genotype with phenotype.
AB - Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon
receptor (AHR) affinity among inbred mouse strains, is an important determinant
of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6
and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for
the rapid identification of DNA sequence differences between Ahr alleles.
Oligonucleotides containing single-base changes at polymorphic sites were
immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA
radiolabeled probes. The observed hybridization patterns demonstrate that this
approach can be used to detect nucleotide differences in the Ahr coding region
with very high accuracy. In parallel experiments, we used a yeast two-hybrid
system to assess phenotypic differences in AHR function. AHR activation, as
measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae
strain SFY526, was determined following treatment with varying doses of the AHR
ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15
fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with
results reported for whole-animal studies than the values observed by in vitro
ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also
confirmed the previously reported observation that an A375V change is principally
responsible for the high- to low-affinity AHR phenotype. There has been no
straightforward method to reliably and reproducibly phenotype large numbers of
humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by
oligonucleotide-hybridization and yeast two-hybrid methodologies will be
invaluable for the rapid and unequivocal determination of changes in DNA sequence
and receptor-ligand affinities associated with human AHR polymorphisms.
PMID- 9637802
TI - Cleaner water: it's elementary.
PMID- 9637803
TI - Regulation of the extracellular ligand binding activity of integrins.
AB - Integrins are a large heterodimeric family of cell surface adhesion receptors
that bind extracellular matrix and cell surface ligands. The extracellular ligand
binding activity of integrins is a dynamic and highly regulated event involving
the induction of conformational changes within the integrin structure. The
adhesive properties of integrins can be controlled by altering the activation
state of the integrin, either through conformational change or receptor
clustering, using mechanisms that are regulated by intracellular proteins. In
this review, we will discuss what is currently known about integrin structure and
the ligand binding sites present within the receptor. In addition, the mechanisms
by which the ligand binding event is regulated through conformational change will
be addressed, and the potential role of intracellular cytoplasmic proteins will
be discussed.
PMID- 9637804
TI - An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among
unvaccinated nursing home residents.
AB - BACKGROUND: Outbreaks of pneumococcal disease are uncommon and have occurred
mainly in institutional settings. Epidemic, invasive, drug-resistant pneumococcal
disease has not been seen among adults in the United States. In February 1996,
there was an outbreak of multidrug-resistant pneumococcal pneumonia among the
residents of a nursing home in rural Oklahoma. METHODS: We obtained
nasopharyngeal swabs for culture from residents and employees. Streptococcus
pneumoniae isolates were serotyped and compared by pulsed-field gel
electrophoresis. A retrospective cohort study was conducted to identify factors
associated with colonization and disease. RESULTS: Pneumonia developed in 11 of
84 residents (13 percent), 3 of whom died. Multidrug-resistant S. pneumoniae,
serotype 23F, was isolated from blood and sputum from 7 of the 11 residents with
pneumonia (64 percent) and from nasopharygeal specimens from 17 of the 74
residents tested (23 percent) and 2 of the 69 employees tested (3 percent). All
the serotype 23F isolates were identical according to pulsed-field gel
electrophoresis. Recent use of antibiotics was associated with both colonization
(relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.2) and disease
(relative risk, 3.6; 95 percent confidence interval, 1.2 to 10.8). Only three
residents (4 percent) had undergone pneumococcal vaccination. After residents
received pneumococcal vaccine and prophylactic antibiotics, there were no
additional cases of pneumonia, and the rates of carriage decreased substantially.
CONCLUSIONS: In this outbreak a single pneumococcal strain was disseminated among
the residents and employees of a nursing home. The high prevalence of
colonization with a virulent organism in an unvaccinated population contributed
to the high attack rate. Clusters of pneumococcal disease may be underrecognized
in nursing homes, and wider use of pneumococcal vaccine is important to prevent
institutional outbreaks of drug-resistant S. pneumoniae infection.
PMID- 9637805
TI - A comparison of rectal diazepam gel and placebo for acute repetitive seizures.
AB - BACKGROUND: Acute repetitive seizures are readily recognizable episodes involving
increased seizure frequency. Urgent treatment is often required. Rectal diazepam
gel is a promising therapy. METHODS: We conducted a randomized, double-blind,
parallel-group, placebo-controlled study of home-based treatment for acute
repetitive seizures. Patients were randomly assigned to receive either rectal
diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight
on the basis of age, or placebo. Children received one dose at the onset of acute
repetitive seizures and a second dose four hours later. Adults received three
doses -- one dose at onset, and two more doses 4 and 12 hours after onset.
Treatment was administered by a care giver, such as a parent, who had received
special training. The number of seizures after the first dose was counted for 12
hours in children and for 24 hours in adults. RESULTS: Of 125 study patients (64
assigned to diazepam and 61 to placebo) with a history of acute repetitive
seizures, 91 (47 children and 44 adults) were treated for an exacerbation of
seizures during the study period. Diazepam treatment was superior to placebo with
regard to the outcome variables related to efficacy: reduced seizure frequency
(P<0.001) and improved global assessment of treatment outcome by the care giver
(frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc
analysis showed diazepam to be superior to placebo in reducing seizure frequency
in both children (P<0.001) and adults (P=0.02), but only in children was it
superior with regard to improvement in global outcome (P<0.001). The time to the
first recurrence of seizures after initial treatment was longer for the patients
receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse
effect of treatment; somnolence was the most frequent. Respiratory depression was
not reported. CONCLUSIONS: Rectal diazepam gel, administered at home by trained
care givers, is an effective and well-tolerated treatment for acute repetitive
seizures.
PMID- 9637806
TI - Effects of metformin on spontaneous and clomiphene-induced ovulation in the
polycystic ovary syndrome.
AB - BACKGROUND: Obese women with the polycystic ovary syndrome are relatively
unresponsive to the induction of ovulation by clomiphene. We hypothesized that
reducing insulin secretion by administering metformin would increase the
ovulatory response to clomiphene. METHODS: We performed oral glucose-tolerance
tests before and after the administration of 500 mg of metformin or placebo three
times daily for 35 days in 61 obese women with the polycystic ovary syndrome.
Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily
for five days while continuing to take metformin or placebo. Serum progesterone
was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have
occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on
any of these days. RESULTS: Twenty-one women in the metformin group and 25 women
in the placebo group were given clomiphene because they did not ovulate
spontaneously during the first phase of the study. Among the 21 women given
metformin plus clomiphene, the mean (+/-SE) area under the serum insulin curve
after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU
per milliliter per minute (40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute,
P=0.03), but it did not change significantly in the 25 women given placebo plus
clomiphene. Nineteen of the 21 women (90 percent) who received metformin plus
clomiphene ovulated (mean peak serum progesterone concentration, 23.8+/-3.4 ng
per milliliter [7.6+/-10.9 nmol per liter]). Two of the 25 women (8 percent) who
received placebo plus clomiphene ovulated (P<0.001). Overall, 31 of the 35 women
(89 percent) treated with metformin ovulated spontaneously or in response to
clomiphene, as compared with 3 of the 26 women (12 percent) treated with placebo.
CONCLUSIONS: The ovulatory response to clomiphene can be increased in obese women
with the polycystic ovary syndrome by decreasing insulin secretion with
metformin.
PMID- 9637807
TI - Use of misoprostol during pregnancy and Mobius' syndrome in infants.
AB - BACKGROUND: Patients with upper gastrointestinal ulceration may be treated with
misoprostol, but it is not recommended for pregnant women because it may
stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent
data from Brazil, where misoprostol is used orally and vaginally as an
abortifacient, have suggested a relation between the use of misoprostol by women
in an unsuccessful attempt to terminate pregnancy and Mobius' syndrome
(congenital facial paralysis) in their infants. METHODS: We compared the
frequency of misoprostol use during the first trimester by mothers of infants in
whom Mobius' syndrome was diagnosed and mothers of infants with neural-tube
defects in Brazil. All diagnoses in infants were made between January 16, 1990,
and May 31, 1996, by clinical geneticists at seven hospitals who also interviewed
the mothers and recorded information about the administration of misoprostol,
among other data. RESULTS: We identified 96 infants with Mobius' syndrome and
matched them with 96 infants with neural-tube defects. The mean age at the time
of the diagnosis of Mobius' syndrome was 16 months (range, 0.5 to 78), and the
diagnosis of neural-tube defects was made within 1 week of birth in most cases.
Among the mothers of the 96 infants with Mobius' syndrome, 47 (49 percent) had
used misoprostol in the first trimester of pregnancy, as compared with 3 (3
percent) of the mothers of the 96 infants with neural-tube defects (odds ratio,
29.7; 95 percent confidence interval, 11.6 to 76.0). Twenty of the mothers of the
infants with Mobius' syndrome had taken misoprostol only orally (odds ratio,
38.8; 95 percent confidence interval, 9.5 to 159.4), 20 had taken misoprostol
both orally and vaginally, 3 had taken the drug vaginally, and 4 did not report
how they took the drug. CONCLUSIONS: Attempted abortion with misoprostol is
associated with an increased risk of Mobius' syndrome in infants.
PMID- 9637808
TI - Images in clinical medicine. Tuberous sclerosis.
PMID- 9637809
TI - Images in clinical medicine. Ash-leaf spots in tuberous sclerosis.
PMID- 9637810
TI - The reproducibility of a method to identify the overuse and underuse of medical
procedures.
AB - BACKGROUND: To assess the overuse and underuse of medical procedures, various
methods have been developed, but their reproducibility has not been evaluated.
This study estimates the reproducibility of one commonly used method. METHODS: We
performed a parallel, three-way replication of the RAND-University of California
at Los Angeles appropriateness method as applied to two medical procedures,
coronary revascularization and hysterectomy. Three nine-member multidisciplinary
panels of experts were composed for each procedure by stratified random sampling
from a list of experts nominated by the relevant specialty societies. Each panel
independently rated the same set of clinical scenarios in terms of the
appropriateness of the relevant procedure on a risk-benefit scale ranging from 1
to 9. Final ratings were used to classify the procedure in each scenario as
necessary or not necessary (to evaluate underuse) and inappropriate or not
inappropriate (to evaluate overuse). Reproducibility was measured by overall
agreement and by the kappa statistic. The criteria for underuse and overuse
derived from these ratings were then applied to real populations of patients who
had undergone coronary revascularization or hysterectomy. RESULTS: The rates of
agreement among the three coronary-revascularization panels were 95, 94, and 96
percent for inappropriate-use scenarios and 93, 92, and 92 percent for necessary
use scenarios. Agreement among the three hysterectomy panels was 88, 70, and 74
percent for inappropriate-use scenarios. Scenarios involving necessary use of
hysterectomy were not assessed. The three-way kappa statistic to detect overuse
was 0.52 for coronary revascularization and 0.51 for hysterectomy. The three-way
kappa statistic to detect underuse of coronary revascularization was 0.83.
Application of individual panels' criteria to real populations of patients
resulted in a 100 percent variation in the proportion of cases classified as
inappropriate and a 20 percent variation in the proportion of cases classified as
necessary. CONCLUSIONS: The appropriateness method is far from perfect.
Appropriateness criteria may be useful in comparing levels of appropriate
procedures among populations but should not by themselves be used to direct care
for individual patients.
PMID- 9637811
TI - Rating the appropriateness of coronary angiography--do practicing physicians
agree with an expert panel and with each other?
AB - BACKGROUND: Evaluations of the appropriateness of medical care are important to
monitor the quality of care and to contain costs and enhance safety by reducing
inappropriate care. Experts' views are usually incorporated into evaluations of
appropriateness. However, practicing physicians may not concur with these views,
and physicians' clinical backgrounds may influence their beliefs. METHODS: We
asked 1058 internists, family practitioners, and cardiologists in California,
Florida, New York, Pennsylvania, and Texas to rate the appropriateness of
coronary angiography after acute myocardial infarction for 20 common indications.
Nine clinical experts also rated these indications using an established consensus
method. RESULTS: For 17 of the 20 indications, median ratings of surveyed
physicians and the expert panel agreed within 1 unit on a 9-unit scale. Patients'
older age had a negative effect on ratings by the expert panel but not on ratings
by surveyed physicians. In multivariable analyses of surveyed physicians,
cardiologists rated angiography as significantly more appropriate than did
primary care physicians for complicated indications, and for uncomplicated
indications cardiologists who performed invasive procedures gave higher
appropriateness ratings for angiography than did cardiologists who did not
perform such procedures and primary care physicians. For uncomplicated
indications, physicians from hospitals providing coronary angioplasty and bypass
surgery rated angiography as more appropriate than physicians from other
hospitals. Physicians from New York and those employed by health maintenance
organizations rated angiography as less appropriate than other physicians.
CONCLUSIONS: Surveyed physicians agreed with clinical experts about the
appropriateness of coronary angiography after myocardial infarction for most
indications, indicating that well-designed expert panels can closely reflect the
views of practicing physicians. Variations in beliefs among practicing physicians
suggest that evaluations of medical practice should incorporate the views of a
range of relevant types of physicians.
PMID- 9637813
TI - Pneumococcal outbreaks in nursing homes.
PMID- 9637814
TI - Gaining a perspective on childhood seizures.
PMID- 9637815
TI - What is appropriate care?
PMID- 9637816
TI - Differential expression of Galalpha1,3Gal epitope in polymeric and monomeric IgM
secreted by mouse myeloma cells deficient in alpha2, 6-sialyltransferase.
AB - IgM are glycoproteins secreted by plasma cells as (mu2L2)5+J or (mu2L2)6
polymers. In most species, mu- and J-chains bear five and one N -glycans,
respectively. Here we compare the terminal glycosylation patterns of 4-hydroxy-3
nitrophenylacetyl (NP)-specific IgM secreted by transfectants of the J558L mouse
myeloma deficient in the alpha2,6 sialyltransferase [alpha2,6ST(N)] or by a
hybridoma expressing this enzyme (B1.8 cells). The absence of alpha2,6
sialylation results in an increased addition of alpha1, 3-galactosyl residues to
mu- and J-chain N-glycans. Since alpha1, 3-galactosyltransferase (alpha1,3Gal-T)
is similarly expressed in the two cell lines, these results indicate that a
competition reaction occurs in vivo between alpha2,6ST(N) and alpha1,3Gal-T. In
the alpha2,6ST(N) deficient transfectants, mu-chains lacking the C-subterminal
Cys575 residue, which are secreted mainly in the form of mu2L2 monomers, are more
efficiently capped by alpha1, 3-galactosyl residues, confirming that
polymerization significantly reduces the accessibility of mu-chain glycans to the
Golgi processing enzymes involved in the biogenesis of antennary sugars.
Functional assays indicate that IgM sialylation affects antigen-binding and
complement-dependent hemolysis of haptenated red blood cells.
PMID- 9637817
TI - [Laboratory media for the cultivation of tubercle bacillus].
AB - A variety of different media for the cultivation of mycobacteria have been
described but a few of them are in use today. Those currently used can be
characterized by three basic types. The first is egg-based media represented by
Ogawa and Lowenstein-Jensen. The second type is agar-based media; the most common
one are Middlebrook 7H10 and 7H11. The third type is liquid media such as
Middlebrook 7H9. Several weeks of incubation may be required for the isolation of
M. tuberculosis on solid media. Substantial improvement in the time to detection
and the recovery rate was realized by using broth-based culture system such as
the BACTEC 460TB, Septi-Chek AFB, MGIT and BACTEC 9000. In the BACTEC 460TB
system, the mycobacteria is detected radiometrically. The processed specimen is
added to a modified 7H9 medium (BACTEC 12B) containing 14C-labeled palmitic acid
and an antibiotic complex, PANTA. Mycobacterial growth can be ascertained by the
liberation of 14CO2 and detected by BACTEC 460TB instrument. The Septi-Chek AFB
is a biphasic medium which combines broth and solid media. The liquid medium is a
modified Middlebrook 7H9 in a carbon-dioxide-enriched culture bottle. After
inoculation of the sample, the bottle is capped with a slide consisting of three
solid media; a non-selective Middlebrook 7H11 agar, an egg-based medium, and
chocolate agar. A novel system is the MGIT, which is a nonradiometric broth
method for the detection of mycobacteria from clinical specimens. The MGIT
consists of a modified Middlebrook 7H9 broth and a sensor embedded in silicone on
the bottom of a tube. The appearance of orange-colored fluorescence in the sensor
when excited indicates the growth of mycobacteria. MB Redox is a modified, serum
supplemented Kirchner medium containing p-indonitrotetrazolium violet (INT) as an
indicator of microbial growth. The INT is reduced by the redox system of the
mycobacteria to deep violet-colored formazan. This substance is water insoluble
and is reduced to the cell surface, by which bacterial clamps can be easily
detected by their violet color. At present, the egg-based media are the first
choice for the culture of clinical samples. However, there are advantages to each
type of medium and not all strains of mycobacteria can be recovered on a single
medium. Therefore, it is recommended that one representative of each type of
medium be used for primary isolation; one example in Japan may be Ogawa egg
medium in combination with Middlebrook 7H11 and MGIT.
PMID- 9637818
TI - [Development of the intratracheal infection model of experimental murine
mycobacteriosis: comparison with the intravenous infection model].
AB - An intratracheal infection method of experimental murine mycobacteriosis was
developed for an in vivo study of antimycobacterial agents. Two models of
intratracheal (IT) and intravenous (i.v.) routes of infection with mycobacteria
of the same inoculum dose were compared in terms of the mean survival days of
mice or bacterial loads in organs during the course of infection. IT model with
either of M. bovis Ravenel, M. tuberculosis Kurono, M. tuberculosis H37Rv or M.
intracellular N-256 exhibited a much more distinct lung-specific infection than
i.v. model with the same dose of respective mycobacterial strains. The
intratracheal infection method presented in this report does not require any
special equipment and is a much safer method for the researcher than airborne
infection. In this model, following slight anesthetizing of mice, bacillary
suspension was injected quantitatively into lungs through the mouth and trachea
by using a specially modified needle set with a short fine polyethylene tube.
This IT model may be useful not only for the in vivo assessment of anti
mycobacterial agents but also for the comparison of virulence among various
mycobacterial strains.
PMID- 9637819
TI - [Diagnostic usefulness of the tuberculin reaction by PPD-B in Mycobacterium avium
complex disease].
AB - This study was carried out to clarify the diagnostic usefulness of the skin tests
of purified protein derivatives from M. intracellulare (PPD-B) and M.
tuberculosis (PPDs). Study subjects consisted of 41 patients with primary
infection type of M. avium complex (MAC) disease, 36 patients with pulmonary
tuberculosis (TB) and 29 patients with other bacterial respiratory infections
including COPD (OB). The patients were sorted out to middle (50-69 y.o.) and old
(70-89 y.o.) age groups of each disease. The size of skin redness elicited 48
hours after the PPD-B and PPDs intradermal injections were compared among them.
The results were as follows. 1) Both PPD-B and PPDs skin reactions were larger in
the middle age group than in the old one for each disease. 2) In PPDs skin tests,
the reaction of TB group was the largest among the three diseases. In PPD-B skin
tests, that of MAC was the largest. 3) In TB group, PPDs skin reaction was
significantly larger than that of PPD-B, while in MAC and OB groups there was no
significant difference between the skin reactions of PPDs and PPD-B. 4) Defining
significant positive reaction to PPD-B as PPD-B skin reaction exceeding 10 mm and
larger than that of PPDs skin reaction, the rate of significant positive reaction
to PPD-B was significantly higher in MAC than TB in both age groups. These
results showed that the simultaneous skin tests of PPD-B and PPDs were a useful
aid in the diagnosis of MAC infection disease when mycobacterial infection
diseases were clinically suspected by bacteriological or chest radiographic
examinations.
PMID- 9637820
TI - [A preventable case who died of miliary tuberculosis after receiving contact
examination].
AB - A 30-year-old-man was admitted to our hospital because of headache and fever. His
consciousness on admission was clouding. Sputum examination was positive for acid
fast bacilli which later identified as Mycobacterium tuberculosis. Chest-X-ray
and computed tomogram on admission showed multiple cavitary lesions on bilateral
upper lung fields and bilateral diffuse nodular shadow. He was diagnosed as
miliary tuberculosis with tuberculous meningitis. His mother admitted because of
pulmonary tuberculosis four months ago, and her sputum examination was smear
positive for acid fast bacilli, Gaffky 4, and she complained of cough for 6
months before admission. Because of this situation, he rapidly underwent the
contact examination with chest X-ray, but not examined by tuberculin skin test
because he was 30-year-old. As then chest X-ray was normal, he was not indicated
of chemoprophylaxis, and he died of miliary tuberculosis and tuberculous
meningitis 4 months after the contact examination.
PMID- 9637821
TI - [Establishment of new diagnostic technique and its clinical application for
nontuberculous mycobacterial infections].
AB - The clinical futures of 52 patients with pulmonary Mycobacterium avium complex
infection (MAC group), 7 M. kansasii infection (MK group), and 5 M. chelonae
infection (MC group) were studied. Aged female was dominant in MAC and MC group,
while middleaged man was dominant in MK group. Although body mass index (BMI) was
the lowest in MAC group, there was no difference between the groups in clinical
sign, symptom, and laboratory data. Type III radiological finding was dominant in
MAC group, while type II in MK and MC groups. Bacteriological eradication rate of
causative organisms was 86% in MK group, 54% in MAC group, and 40% in MC group.
However, the relation between clinical efficacy of chemotherapy, BMI, serum
protein level, and cavity formation in chest radiogram was not observed. MAC was
detected in clinical samples such as sputum, bronchial washing fluid, and gastric
juice with 5 to 10% in frequency by Amplicor, one of commercially available PCR
detection kits for mycobacteria. Furthermore 60% to 80% of the MAC positive cases
were diagnosed and treated as nontuberculous mycobacteriosis. Although MAC is
occasionally exist in oral cavity or clinical environment, the positive result of
genetic diagnostic method such as Amplicor should be carefully considered.
PMID- 9637822
TI - [The short-term effects of multidrug chemotherapy for pulmonary Mycobacterium
avium-intracellulare complex (MAC) infection].
AB - In performing MAC chemotherapy, we are faced with the following two problems:
first, unlike for Mycobacterium tuberculosis, we have neither any suitable
bacteriocidal drugs nor bacteriocidal regimens for MAC treatment; secondly, in
case of MAC, unlike in the case of Mycobacterium tuberculosis, in vitro
sensitivity does not correlate with in vivo sensitivity. For these reasons, we
find difficulty in planning a rational protocol for MAC treatment, and thus
depend on previous experiences of other physicians in MAC chemotherapy. Here, we
have tried to evaluate such previous experiences objectively, and studied
retrospectively the effects of previous combination chemotherapy cases of
pulmonary MAC infections at National Tokyo Hospital. We selected 170 cases which
had received the same chemotherapy continuously over a period of six months.
Concentration of bacilli cultured, 8 weeks in Ogawa solid egg containing medium
was translated semi-quantitatively to colony forming units (CFU) according to the
Japanese guideline for acid fast bacilli test. Having set a mean CFU of 3 times
sputum culture before treatment as 100%, we calculated a six month sequential
bacillary response to a regimen and plotted the bacillary response curves. The
response curve of the total 170 MAC treatment cases exhibits a minimum point of
42.9% at 2 months, and subsequently rises to 71.1% after six months compared to
the state before treatment. The response curves of various regimens of multidrug
chemotherapy indicate that combinations of more than 3 drugs including
aminoglycoside and clarithromycin are most effective. However, although some
effectiveness is indicated, neither the present drugs nor regimens are capable to
achieve a bacteriocidal effect in MAC treatment.
PMID- 9637823
TI - [Geographical distribution of Mycobacterium avium complex in environment and
serovars of Mycobacterium avium complex isolates from patients with and without
AIDS].
AB - Mycobacterium avium complex (MAC) organisms have been isolated from water and
soil. It is now generally accepted that environmental sources, especially natural
waters, are the reservoirs for most human infections caused by MAC. Previously,
we reported that M. avium and M. intracellular were distributed predominantly in
the eastern and western part of Japan, respectively. To clarify the factor(s) of
the difference, the following experiment was undertaken. MAC was isolated from
soil samples collected in Tokai, Kinki and Chugoku districts, by the method of
Ichiyama et al. MAC isolates were identified by AccuProbe Confirmation and
Identification tests, together with some conventional tests. Seven (11.7%) of 60
isolates were identified as M. avium, twenty (33%) as M. intracellulaer and 33
(55%) as MAC-like organisms. Therefore, it was not found that the difference in
the geographical distribution between soil MAC and disease-associated MAC. MAC
like strains possess MAC-specific alpha antigen, and biological and biochemical
features of MAC. They reacted with the AccuProbe MAC but not with the AccuProbe
M. avium and M. intracellulare. Sequencing analysis of 16s RNA gene implies that
MAC-like strains show an intermediate sequence pattern of M. avium and M.
intracellulare. HPLC patterns of these strains were compatible with those of MAC.
It is known that the major serovars of MAC isolates from patients with or without
AIDS are different. Serological aspects in this respect are not yet elucidated
well in Japan. The major serovars of MAC from patients with AIDS are 4 and 8 in
the USA and Australia, 6 and 4 in Sweden, and 8/21 and 8 in Germany. On the other
hand, the major serovars of MAC from patients without AIDS are 8 and 16 (15) in
the USA and 6 and 1 in Sweden. According to out recent study the major serovars
of MAC from non-AIDS patients are 1 and 8 in the eastern part and 16 and 14 in
the western part of Japan. In the present study, 38 MAC isolates from sputum,
stool and blood and AIDS patients were identified. All of the isolates were
identified as M. avium. Serovars of 15 strains were 4 (4 strains), 8 (3 strains),
9 (3 strains), 3 (2 strains), Darkin (2 strains) and 1 (1 strain). Therefore, it
seems that the major serovars of the Japanese MAC strains from AIDS patients are
similar to those of the American MAC strains from such patients.
PMID- 9637824
TI - Subgenus classification of Acanthamoeba by riboprinting.
AB - Subgenus classification of Acanthamoeba remains uncertain. Twenty-three reference
strains of Acanthamoeba including 18 (neo)type-strains were subjected for
classification at the subgenus level by riboprinting. PCR/RFLP analysis of 18S
rRNA gene (rDNA). On the dendrogram reconstructed on the basis of riboprint
analyses, two type-strains (A. astronyxis and A. tubiashi) of morphological group
1 diverged early from the other strains and were quite distinct from each other.
Four type-strains of morphological group 3, A. culbertsoni, A. palestinensis, A.
healyi were considered taxonomically valid, but A. pustulosa was regarded as an
invalid synonym of A. palestinensis. Strains of morphological group 2 were
classified into 6 subgroups. Among them, A. griffini which has an intron in its
18S rDNA was the most divergent from the remaining strains. Acanthamoeba
castellanii Castellani, A. quina Vil3, A. lugdunensis L3a, A. polyphaga Jones, A.
triangularis SH621, and A. castellanii Ma strains belonged to a subgroup, A.
castellanii complex. However, A. quina and A. lugdunensis were regarded as
synonyms of A. castellanii. The Chang strain could be regarded as A. hatchetti.
Acanthamoeba mauritaniensis, A. divionensis, A. paradivionensis could be
considered as synonyms of A. rhysodes. Neff strain was regarded as A. polyphaga
rather than as A. castellanii. It is likely that riboprinting can be applied for
rapid identification of Acanthamoeba isolated from the clinical specimens and
environments.
PMID- 9637825
TI - The first discovery of larval Gnathostoma hispidum (Nematoda: Gnathostomidae)
from a snake host, Agkistrodon brevicaudus.
AB - The present study was performed to observe the infection status of several kind
of animals with indigenous Gnathostoma in Korea, and morphological
characteristics of gnathostome larvae detected from pit-viper, Agkistrodon
brevicaudus, for the species identification. To know the existence of Gnathostoma
in Korea, 3,450 loaches, 24 bullfrogs, several kinds of snakes, i.e., 55 Elaphe
rufodorsata, 2 Dinodon rufozonatum rufozonatum, 62 Rhabdophis tigrinus tigrinus
and 87 Agkistrodon spp., and 438 cats were examined. A total of 21 larval
gnathostomes was detected from 12 pit-vipers, A. brevicaudus. They were 2,233 x
0.343 mm in average size and covered with about 210 transverse rows of minute
cuticular spines. Their characteristic head bulbs were provided with 4 rows of
hooklets of which average numbers in each row were 36.8, 39.0, 41.7 and 44.3,
posteriorly. In the cross sections of midgut level, the intestinal wall consisted
of a single layer of 19-25 elongate epithelial cells with a single nucleus. SEM
observation of the larvae revealed unique features of head bulb, cuticular spines
on transverse striations and a cervical papilla. On the basis of above
morphological characteristics, they were identified as the advanced third-stage
larvae of Gnathostoma hispidum. It was first confirmed that the pit-viper,
Agkistrodon brevicaudus is the snake intermediate host of G. hispidum.
PMID- 9637826
TI - Life history of Echinoparyphium recurvatum (Trematoda: Echinostomatidae) in
Korea.
AB - The present study was performed to observe characteristics of the life history of
Echinoparyphium recurvatum under both natural and laboratory conditions in Korea.
A batch of Radix auricularia coreana was collected from Sunamchon, one of the
stream of West Naktonggang (River), in Kangso-gu, Pusan during August and
September 1992. Out of 106 snails examined by crushing, 52 (49.0%) were infected
with larval E. recurvatum, i.e. rediae, cercariae and metacercariae. Cercariae
naturally shed from snails encysted in the snails of same species and loaches,
but not in mud-snails. Adult worms were detected from chicks and ducks
experimentally infected with metacercariae, but not from rats and mice. The
average recovery rate of adults from chicks was 13.1%. Rediae were sac-like,
2.437 x 0.317 mm in average size, with a muscular pharynx and a brownish cecum
which reached the anterior half of the body. Cercariae consisted of a spindle
shaped body (0.262 x 0.129 mm in average) and a rod-like tail (0.528 x 0.056 mm
in average). In the cercarial body, 45 collar spines were observed on the head
crown, and double rows of excretory ducts with fine granules were laterally
arranged between the pharynx and the ventral sucker. Metacercariae were
spherical, 0.144 x 0.142 mm in average size, with thick hyaline outer and thin
elastic inner walls, and many excretory granules. Adults were slender and more
attenuated in the anterior end, 2.760 x 0.550 mm in average size, and had 45
collar spines including four end group spines on both ventral corners. From the
above results, it was confirmed that R. auricularia coreana plays a pivotal role
in the life cycle of E. recurvatum as the first and/or second intermediate hosts
in Korea.
PMID- 9637827
TI - Viability of eggs, filariform larvae and adults of Strongyloides venezuelensis
(Nematoda: Strongyloidea) maintained in vitro.
AB - The present study was performed to check the viability of eggs, filariform larvae
and adults of Strongyloides venezuelensis exposed to various conditions for an in
vitro maintenance. The eggs in the feces remained viable for about 25 days at 4
degrees C and 15 days at room temperature. However, the isolated eggs in sterile
saline lost their viability within 24 hr at 4 degrees C. The eggs in morula stage
were very sensitive to air drying and rapidly lost their viability (< or = 12
hr). Filariform larvae survived for a maximum period of 45 days in fecal
suspension and 28 days in 0.12% nutrient broth in polyvinyl culture bags
maintained at 20 degrees C. On the other hand, those isolated from nutrient broth
cultures survived for a maximum period of 32 days in tap water and 22 days in
sterile saline at 20 degrees C. The mature adult worms obtained from
experimentally infected rats survived maximally for 9 days in serum supplemented
(10% rat-serum) 0.12% nutrient broth and 4 days in serum free nutrient broth at
37 degrees C while the culture media were changed at an alternate day. The adult
female worms deposited fertile eggs in serum supplemented and serum free nutrient
broth cultures, however, the hatched larvae (L1) were not able to develop to the
filariform stage in the culture media and found to die within 24 hr of
maintenance. The present findings on an in vitro maintenance of different stages
of S. venezuelensis may provide useful information for biological and biochemical
studies with Strongyloides species.
PMID- 9637828
TI - Intestinal mastocytosis and goblet cell hyperplasia in BALB/c and C3H mice
infected with Neodiplostomum seoulense.
AB - Mucosal mast cell (MMC) and goblet cell (GC) responses were observed in the small
intestine of two strains of mice (BALB/c and C3H) infected with Neodiplostamum
seoulense, and their roles in the host defense and worm expulsion were studied.
From day 3 to 28 post-infection (PI) with 200 metacercariae, the worm recovery
rate from BALB/c mice was consistently and remarkably higher than that from C3H
mice. In the duodenum of both strains of mice, the main habitat of the flukes,
mastocytosis was pronounced on day 7 PI but quickly diminished thereafter.
Similar kinetics were observed in the jejunum and ileum, although the extent of
mastocytosis was lesser in the ileum than other two areas. These MMC kinetics
were not different between the two strains of mice. Moreover, the extent of
mastocytosis was stronger in BALB/c mice than in C3H mice. GC hyperplasia was
remarkable in the duodenum of BALB/c mice throughout the course of infection
except day 14 PI, whereas it was recognizable only in the jejunum and ileum of
C3H mice on day 7 PI. Mucin activation was evidently demonstrated in both strains
of mice throughout the course of infection, but more marked in BALB/c than in C3H
mice. The results strongly suggest that mastocytosis and GC hyperplasia are local
immune responses against N. seoulense, however, they play a minor role in the
host defense and worm expulsion.
PMID- 9637829
TI - Immunosuppressive effect of Cryptosporidium baileyi infection on vaccination
against Newcastle disease in chicks.
AB - Hemagglutination-inhibition titers (log2) to Newcastle disease (ND) virus were
chronologically observed in chicks, which were orally inoculated with 5 x 10(5)
oocysts of Cryptosporidium baileyi at 2 days of age and subsequently vaccinated
with inactivated ND virus at 4 and 21 days postinoculation. In general, the
titers were considerably lower in the infected chicks than those in the
uninfected control throughout the experimental period (p < 0.01), and rapid
negative seroconversions were observed in the infected chicks. The titers reached
a peak on weeks 2 and 4 post-booster-vaccination in the control and infected
chicks, respectively. Thus, C. baileyi infection was shown to have an
immunosuppressive effect on ND vaccination when the agent was given to 2-day-old
chicks. It is suggested that C. baileyi infection in chicks may increase the host
susceptibility to ND virus.
PMID- 9637830
TI - The effect of heterogeneous hyperimmune IgG antibody on prophylaxis and treatment
of Pneumocystis carinii infection in rats.
AB - Immunotherapy has been used in support of trimethoprim-sulfamethoxazole treatment
for Pneumocystis carinii pneumonia. The present study investigated the
therapeutic or preventive effects of heterogeneous hyperimmune IgG antibody (HIA)
in experimental rats. Their immunity was suppressed by steroid injection, and
they were also injected peritoneally with HIA which reacted with 40-55, 92, 116,
and 200 kDa bands of the crude antigen. All rats were infected by P. carinii and
the cystic forms on lung impression smears were counted. The count was 20.5-76.5
(mean 52.5 + 19.3) in those which received steroid only, but decreased to 6.0
21.0 (mean 13.5 + 10.6) in those of group 3 which received HIA for the same
duration. In other groups, the mean count ranged from 29.9 + 32.9 to 54.1 + 47.7,
and in those which received 13.7 mg HIA the reduction effect was greater than in
those which received 6.8 mg or 20.5 mg HIA. The present finding confirmed that in
rats during the early stage of infection, the heterogeneous HIA to MSG antigen
bands had a partial effect on P. carinii pneumonia, both prophylactically and
therapeutically.
PMID- 9637831
TI - Isolation and characterization of a 40 kDa cysteine protease from Gymnophalloides
seoi adult worms.
AB - A 40 kDa cysteine protease was purified from the crude extract of adult worms of
Gymnophalloides seoi by two consecutive steps: Sephacryl S-200 HR and DEAE
Sephacel chromatography. Enzyme activities were completely inhibited by cysteine
protease inhibitors. L-trans-epoxysuccinylleucylamido (4-guanidino) butane (E-64)
and iodoacetic acid, strongly suggesting that the purified enzyme belongs to the
cysteine family of proteases. The enzyme was maximally active at pH 4.5 in 0.1 M
of buffer, and its activity was greatly potentiated in the presence of 5 mM
dithiothreitol. The protease degraded macromolecules with differential
capabilities; it degraded extracellular matrix proteins, such as collagen and
fibronectin, with a stronger activity against collagen than fibronectin. However,
the enzyme digested hemoglobin and human immunoglobulins only slightly, leaving
them nearly intact after an overnight reaction. Our results suggest that the
cysteine protease of G. seoi adults is potentially significant in the nutrient
uptake from the host intestine.
PMID- 9637832
TI - A relapsed case of imported tertian malaria after a standard course of
hydroxychloroquine and primaquine therapy.
AB - Resistance of Plasmodium species to antimalarial agents has become increasingly
challenging to the management and prevention of malaria. We experienced an
imported case of tertian malaria due to Plasmodium vivax relapsed after a
seemingly successful treatment with conventional course of hydroxychloroquine and
primaquine. A 35-year-old man developed fever three days after return from India
and mainland China. After his illness was diagnosed as tertian malaria, he was
managed with hydroxychloroquine and then primaquine (primaquine base 15 mg/day
for 14 days). Thereafter peripheral blood smears showed no malarial parasites,
and there was no relapse of symptom until the 55th post-treatment day, however,
six months after the above treatment tertian malaria relapsed. He was managed
with the same medications again and malaria did not relapse for 10 months.
PMID- 9637833
TI - Detection of Cryptosporidium oocysts in canine fecal samples by
immunofluorescence assay.
AB - Fecal samples were collected from 257 dogs in four areas in Korea during the
period of January 1996 to November 1997 and examined by immunofluorescence assay
for Cryptosporidium oocysts using a commercial diagnostic kit (Meridian
Diagnostics, Cincinnati, Ohio). Of the 257 samples, 25 (9.7%) were positive for
Cryptosporidium. Differences were noted in the prevalence of canine
cryptosporidiosis in both areas and dog types. The results provide a further
evidence of environmental contamination and widespread distribution of the
parasite in Korea.
PMID- 9637834
TI - [One-stage repair of interrupted aortic arch with selective cerebral perfusion].
AB - To minimize the neurological compromise after the circulatory arrest, the
selective cerebral perfusion could be beneficial. We underwent one-stage repair
of the interrupted aortic arch (IAA) with various intracardiac anomalies for the
six patients, age ranging from 12 days to 4 months, by using the selective
cerebral perfusion. Cardiopulmonary bypass was established by using two-way
arterial cannulation supported by the two respective pump systems, one of which
utilized the EPTFE graft anastmosed to either the bracheocephalic artery or the
right subclavian artery and second of which enrouted through the arterial ductus
to the descending aorta. The cerebral perfusion during the circulatory arrest for
the aortic arch repair was maintained by the selective perfusion via EPTFE graft
with 10 ml/kg/min blood flow. After the completion of the arch repair, the total
system perfusion was restarted through the graft and the repair of the
intracardiac anomalies was followed. Of six, no operative death or neurological
complications related to the operation were found. The clinical neurological
evaluation after operation also demonstrated the normal for the age. In
conclusion, the selective cerebral perfusion by using the EPTFE graft during the
circulatory arrest might decrease the risk of brain damage.
PMID- 9637835
TI - [A case of fulminant myocarditis treated by ABIOMED BVS 5000 biventricular
support].
AB - Reported is a case of acute fulminant myocarditis with profound circulatory
compromise. The patient was supported with biventricular assist devices (BVS 5000
; ABIOMED Inc., Danvers, Mass.). The patient had remarkable recovery of
ventricular function, which allowed for the removal of the device after 269 hours
of support and the recovery to the normal quality of life. This case shows the
success of mechanical support to treat potentially fatal disease process.
PMID- 9637836
TI - [Three cases of pulmonary dirofilariasis suspected of lung cancer].
AB - We experienced with three patients with pulmonary dirofilariasis found in
resected lungs. Two patients showed abnormal shadows on chest roentgenograms
without symptoms. Another patients had chest discomfort. All patients underwent
diagnostic thoracotomy. Histopathological examination showed necrotic
granulomatous lesions surrounded by fibrous tissue and transverse section of
Dirofilaria immits was found. It has been an increasing reported disease. It is
important to keep in mind the possibility of dirofilariasis.
PMID- 9637837
TI - [A case report of pulmonary embolectomy using an endoscope for the detection of
residual emboli].
AB - A 61-year-old woman was transferred to our hospital because of palpitation,
tachypnea and repeated syncopal attack. On admission, sinus tachycardia and
hypoxia were noted without deterioration of consciousness. The diagnosis of
pulmonary embolism was made by pulmonary angiography and right heart
catheterization showing multiple pulmonary emboli and pulmonary hypertension. An
emergent pulmonary embolectomy was performed under total cardiopulmonary bypass.
Residual emboli of bilateral pulmonary arteries were detected with a fiberoptic
choledochoscope and removed carefully with forceps. Pulmonary angioscopic
evaluation appears to be safe and useful for direct visual detection of emboli
and completion of embolectomy.
PMID- 9637838
TI - [Primary large cell carcinoma of the lung in the patients undergoing pulmonary
resection: a comparison between pre- and post-operative diagnosis].
AB - Between 1981 and 1995, 591 patients with primary lung cancer underwent
operations. Of these, 19 patients (3.2%) was diagnosed as a large cell carcinoma
pathologically. Clinicopathologically, we analyzed a discrepancy between pre- and
post-operative diagnosis of these patients. This study showed as follows: 1)
Accuracy of preoperative diagnosis was 73.7%; 2) No patients with primary site in
right upper lobe had a correct diagnosis; 3) Accuracy of preoperation was not
depending on tumor size; 4) In retrospective findings of the biopsied specimens,
'incomplete glandular differentation' caused preoperative diagnosis to
adenocarcinoma, and modification of the specimens by pneumonia caused it to
squamous cell carcinoma; 5) Inadequatespecimens originated from the right upper
lobe or pneumonia lobe; 6) The five-survival rate was 27.3%.
PMID- 9637839
TI - [The long-term anterior chest wound pain after the cardiac surgery].
AB - We discussed on the long-term anterior chest wound pain after the cardiac surgery
by using a questionnaire. The risk of the left anterior chest wound pain was high
significantly in the cases using the left internal thoracic artery compared with
other cases. Participation of the division of the left upper pericardium and the
adjacent soft tissue was highly suggested as the cause of this pain.
PMID- 9637840
TI - [Outcome of emergency surgery for Stanford type A aneurysms: selection of
operative procedures and supported systems of cerebral protection].
AB - Fourteen surgical cases of acute dissecting aneurysms of Stanford type A were
reported. Clinical symptoms, operative methods, pathophysiology, cerebral
protection, supported systems, and prognosis were examined. All patients
underwent surgery within 5 days of symptom onset. The patient population
consisted 8 males and 6 females with a mean age of 56.6 years. Ascending aortic
replacement was performed using a vascular graft 12 patients. ECC was performed
under deep hypothermia. Femoral artery cannulation and retrograde cerebral
perfusions was performed in all cases. The ascending aorta was the site of entry
in 13 of the 14 cases. Whenever feasible, enhanced CT and aortography were
performed to confirm the entry lesion. Two patients expired. One patient died
intraoperatively due to massive bleeding. The other patient, while hospitalized,
experienced a cerebrovascular accident and died due to pneumonia. All other
patients ran an uneventful post-operative course without cerebrovascular
accident. In conclusion we think that although ascending aorta replacement using
prosthetic grafts is not ideal for patients with Stanford type A dissecting
aneurysms, it is a viable option for emergency cases. We found retrograde
circulatory cerebroplegia (RCCP) to be satisfactory for brain protection during
these emergency procedures.
PMID- 9637841
TI - [Prospective study on evaluation of the ischemic heart disease for preoperative
patients with lung cancer].
AB - One hundred twenty-four patients with lung cancer undergoing operation in our
hospital were prospectively studied on evaluation of the ischemic heart disease
before operation. They performed master double electrocardiogram and exercised T1
scintigram before operation. The patient with positive master double
electrocardiogram and/or exercised T1 scintigram was taken into high risk group.
All patients in high risk group performed coronary angiography. This high risk
group consisted of 37 patients (29.8%), including 6 single vessel disease (4.8%),
2 double vessel disease (1.6%), and 1 triple vessel disease (0.8%). Preoperative
revascularization was done 8 patients (6.5%). These revascularization patients
had uneventful course during and after lung operation. However 2 cases of
vasospastic angina (VSA) occurred in non-risk group during operation. It was
impossible to anticipate VSA before lung operation in our series. Therefore our
preoperative evaluation and care of organic ischemic heart disease was effective
in preventing cardiac complications.
PMID- 9637842
TI - [Comparative studies of video-assisted thoracoscopic surgery versus thoracotomy
for primary spontaneous pneumothorax].
AB - Between April 1992 and March 1997, 32 patients with primary spontaneous
pneumothorax were operated in our institution. In the first three years, 9
patients underwent thoracotomy which was classified into two groups axillary
thoracotomy group (AX group) in 5 cases and postero-lateral thoracotomy group (PL
group) in 4 cases. In the recent two years, 23 consecutive patients underwent
video-assisted thoracoscopic surgery (VATS group). The operating time,
intraoperative blood loss, serum CRP and CK level, the duration of the indwelling
chest tube, postoperative hospital stay, the duration of epidural anesthesia,
complications and recurrences were compared among the three groups. The CRP level
was significantly lower in VATS group than in both AX group and PL group. The
duration of indwelling chest tube and postoperative hospital stay were
significantly less in VATS group than in both AX group and PL group. There was no
significant difference in complications and recurrences among the three groups We
conclude from findings that VATS is superior to thoracotomy in the treatment of
primary spontaneous pneumothorax. However more careful intraoperative
manipulation is required to prevent postoperative recurrence.
PMID- 9637843
TI - [A case report of mycotic aneurysms of descending thoracic aorta].
AB - A rare case of mycotic aneurysms of descending thoracic aorta is presented. A 63
year-old man was admitted with history of persistent high fever and loss of
consciousness to our hospital. On admission, there were elevated WBC and CRP.
Blood and spinal fluid cultures revealed growth of Streptococcus pneumonia.
Despite of antibiotic therapy for meningitis and bacteremia, inflammatory sign
continued, and new abnormal shadow appeared on chest X-ray. Chest CT and
aortography showed two aneurysms of descending thoracic aorta. In an emergency
operation, there was no abscess formation around the aneurysms. Aneurysms were
excised en bloc without opening aneurysms followed by in situ Dacron tube graft
replacement. The patient has been doing well without infection.
PMID- 9637844
TI - [The long-term result of an adult case of transposition of the great arteries
corrected with Rastelli operation at the age of thirty-two years].
AB - A 32-year-old woman with transposition of the great arteries was referred to us
for corrective surgery. She had severe cyanosis, dyspnea, and hemoptysis. The
cardiac catheter study and echocardiography revealed that she had transposition
of the great arteries, associated with atrial septal defect, ventricular septal
defect, patent ductus arteriosus, and pulmonary stenosis. Rastelli operation was
performed using equine pericardial roll with three valves made from autologous
pericardium. After the operation she gave birth to two children without any
symptom. Ventricular tachycardia occurred several times but was controlled by the
drug. Eight years after the operation she underwent catheter study. Although the
right ventricular pressure was 80 mmHg and the pressure gradient through the
conduit was 38 mmHg, her general clinical condition was fairly good. We think the
late postoperative result of this patient is satisfactory as an adult case of
transposition of the great arteries.
PMID- 9637845
TI - [An aortic valve-sparing procedures (remodeling) for a patient with annuloaortic
ectasia: a case report].
AB - A 51-year-old man with annuloaortic ectasia and aortic regurgitation, who did not
have Marfan syndrome, underwent an aortic valve-sparing root reconstruction
(remodeling). All three sinuses were excised and then the ascending aorta was
replaced with a 30 mm collagen-impregnated Dacron graft, one of which ends were
scalloped to reproduce pseudosinus. Each coronary artery orifice was anastomosed
to the graft with Carrel patch method. Post-operative angiogram showed no aortic
regurgitation and no pseudosinus formation, because the graft was slightly larger
than the optimal one. The NYHA functional class has been improved III to I 18
months after the operation.
PMID- 9637846
TI - [An experience with St. Jude medical prosthetic 19A-HP which resulted in
restricted opening at an early stage after operation].
AB - St. Jude medical hemodynamic plus series is positively used for aortic valve
replacement (AVR) of small orifice because it can increase the orifice area by
26% compared with conventional prosthetic valves of the same size. We performed
AVR with SJM 19A-HP on a patient having aortic stenosis with regurgitation using
horizontal mattress suturing technique. The aortic orifice size was 18.9 mm at
the preoperative measurement. The course after the operation was uneventful until
9 days after the operation when cinefluoroscopy revealed symmetrical restriction
of opening of valve leaflets. We are now monitoring the clinical course at the
patient has not developed any symptoms though the LV-Ao pressures gradient is 60
mmHg by Doppler echocardiography. As the restriction of valve leaflet opening was
symmetrical, it is not likely that an excess of the ligature or remnant caused
the restriction; structural problems of St. Jude medical prosthesis appear to be
a more reasonable explanation. Since the orifice ring of this prosthesis is not
reinforced, longitudinal forces applied to the hinge may alter the shape of the
ring, thus restricting the movement of valve leaflets. In the present case,
forced insertion of 19A-HP instead of more desirable 17-HP is considered to have
caused longitudinal forces acting on the hinge.
PMID- 9637847
TI - [Malignant recurrence of solitary fibrous tumor of the pleura developed 20 years
after the surgery: a case report of re-extirpation].
AB - A 63-year-old female developed the chest wall tumor protruding into the right
thoracic cavity. She consulted our hospital complaining of chest pain. 20 years
before this episode, she had undergone tumor extirpation combined with the
partial resection of adherent anterior chest wall and the diaphragm for large
benign solitary fibrous tumor of the pleura. Because of the difficulty in making
diagnosis by needle biopsy, operation (re-tumor extirpation combined with the
chest wall) was done. Histological examination revealed that the tumor was
malignant solitary fibrous tumor. We concluded that the tumor was the malignant
recurrence of the benign solitary fibrous tumor resected 20 years before.
Occasionally, benign solitary fibrous tumor of the pleura recurs and behaves more
aggressively than primary, but such a long latent period as 20 years is quite
uncommon. So we present the case and the review of the literature.
PMID- 9637848
TI - [A case of bronchial mucoepidermoid carcinoma treated with right sleeve middle
lobectomy].
AB - We reported one case of a 26-year-old woman in whom mucoepidermoid carcinoma of
the right middle lobe bronchus was successfully treated by bronchoplasty. The
patient complaining fever and cough was admitted to our hospital and the
bronchoscopic examination revealed a tumor mass occluding the right middle lobe
bronchus. Thus, sleeve middle lobectomy was performed. The histological
examination of the resected material revealed a low-grade malignant
mucoepidermoid carcinoma with no lymphatic metastasis. The patient has been well
and free of recurrence for one year postoperatively. In this case, sleeve
lobectomy is approved of an effective method for local curability and
preservation of respiratory function.
PMID- 9637849
TI - [Primary clear cell carcinoma of the lung: report of an operative case].
AB - The patient was a 75-year-old man complaining of cough in July 1996. Chest X-ray
demonstrated a tumor in the left S6. Percutaneous lung biopsy specimen revealed
lung cancer. On September 4, 1996, left lobectomy (R 2 a) was performed. The
tumor was 3.8 x 3.2 x 2.1 cm in size and showed a white yellow solid mass
(pT2N0M0, pStage I, p1d0e0pm0). The pathological examination was confirmed no
differentiation in adenocarcinoma and squamous cell carcinoma. More than 90% of
the tumor cells were characterized as having large clear cytoplasm. On
immunohistochemical study, the tumor cells expressed positive with EMA, CEA,
cytokeratin and negative with vimentin. The postoperative findings showed no
presence of renal cell carcinoma. As the result, a diagnosis of primary clear
cell carcinoma of the lung was made. The postoperative course is uneventful.
PMID- 9637850
TI - [An adult case of intrathoracic chest wall type lipoma by VATS resection].
AB - A 48-year-old woman without symptoms was pointed out an abnormal shadow on chest
X-ray film taken at the mass survey. Image diagnosis led to intrathoracic chest
wall type lipoma. The tumor was surgically removed by video assisted
thoracoscopic surgery (VATS), and the diagnosis of lipoma pathohistologically.
VATS resection was an useful procedure for intrathoracic lipoma because VATS
itself must be less invasive and lipoma was not invasive. CT and MRI were useful
for evaluation of extent of tumor, but not effective for differential diagnosis
of liposarcoma from lipoma. So surgical resection by VATS should be considered,
if possible.
PMID- 9637851
TI - [A case report on surgery for chylothorax after anterior spinal fusion:
usefulness and effectiveness of intraoperative milk administration and
postoperative OK-432 administration].
AB - A 75-year-old man of chylothorax after anterior spinal fusion successfully
underwent thoracoabdominal operation in order to ligate chyloleakage. Not only
preoperative milk intake but also intraoperative administration of milk through
nasogastric tube was useful for identification of the site of leakage. OK-432 was
administered through locally placed and chest tube after operation, after which
residual chyloleakage was stopped. lntraoperative administration of milk through
nasogastric tube was useful and OK-432 injection through topical and chest tube
may be effective, these should be recommended for management of chylothorax.
PMID- 9637852
TI - Public health protection vs. informed consent.
PMID- 9637853
TI - Cancer clusters. What role for epidemiology?
PMID- 9637854
TI - Minnesota's elite bug busters.
PMID- 9637855
TI - Antimicrobial resistance. Guidelines for the primary care physician.
AB - Antimicrobial resistance is an important issue when treating patients with
various bacterial, fungal, protozoal, and viral infections. Until recently, the
focus of concern was on nosocomially acquired infections. However, organisms
causing common community-acquired infections have now developed antimicrobial
resistance. This paper provides a brief overview of this emerging global threat
and discusses resistance in gram-positive organisms, outpatient and antibiotic
use, and strategies to reduce antibiotic overuse. Curbing the overuse of
antibiotics is crucial to reversing the increase in drug-resistant bacteria. We
need to develop guidelines and educate physicians and the public on the use of
antibiotics for respiratory syndromes with predominantly viral etiologies.
PMID- 9637856
TI - An epidemiologic summary of the AIDS/HIV epidemic in Minnesota.
AB - A cumulative total of 3,202 AIDS cases and 2,355 non-AIDS cases of HIV infection
have been diagnosed in Minnesota and reported to the Minnesota Department of
Health since 1982. The number of AIDS cases and HIV infection cases diagnosed
annually peaked five to 10 years ago. New treatments for HIV infection have led
to a marked reduction in mortality. The number of deaths due to AIDS/HIV in 1997
(76) was the lowest number in Minnesota since 1986. Several trends continue to
evolve in reported AIDS/HIV cases. First, the proportion of female cases has
increased over time. Second, male-to-male sex remains the most common exposure
category, but the proportion has declined over time. In contrast, the proportion
of cases related to injecting drug use and heterosexual contact has increased
over time. Third, an increasing proportion of AIDS/HIV patients are black.
Although progress has been made in reducing AIDS/HIV incidence, more Minnesotans
are living with AIDS/HIV than ever before.
PMID- 9637857
TI - Epidemiology in Minnesota. Alcohol epidemiology. Reporting and collecting data on
use in Minnesota.
PMID- 9637858
TI - Etiology, prevention, and treatment of breast, prostate, colorectal, and lung
cancer.
PMID- 9637859
TI - Trends in cardiovascular disease in Minnesota.
PMID- 9637860
TI - Issues in environmental health epidemiology.
PMID- 9637861
TI - Training infectious disease epidemiologists for the next millennium. The
epidemiology program at the University of Minnesota.
PMID- 9637862
TI - Injury epidemiology. Prevention and control of a major public health problem.
PMID- 9637863
TI - Occupational epidemiology in Minnesota.
PMID- 9637864
TI - Reducing smoking among Minnesota teens in managed care. Smoking.
PMID- 9637865
TI - The role of epidemiology in the court.
PMID- 9637866
TI - Commerce in organ transplantation.
PMID- 9637867
TI - Manic-depressive illness from 1936 to 1996: diagnostic modalities, social
attitudes, and therapeutic options.
PMID- 9637868
TI - The case of the president's polyp: portrayal of pathologists in the media.
PMID- 9637869
TI - Can managed care be managed? Some agnostic reflections.
PMID- 9637870
TI - Rhabdomyolysis in antiquity. From ancient descriptions to scientific explication.
PMID- 9637871
TI - Medical cannibalism in China: the case of ko-ku.
PMID- 9637872
TI - Dartmouth Medical School bicentennial symposium. Great issues for medicine in the
twenty-first century: a consideration of the ethical and social issues arising
out of advances in the biomedical sciences.
PMID- 9637873
TI - Inequalities and antivirals.
PMID- 9637874
TI - Fire, blood, and the lion of the Union: Joshua Chamberlain's Civil War ailments.
PMID- 9637875
TI - Three for the record.
PMID- 9637876
TI - The death of Socrates.
PMID- 9637877
TI - Reflections on the question: where is the sacrifice?
PMID- 9637878
TI - Medical role models.
PMID- 9637879
TI - [Present state of Japan Marrow Donor Program].
PMID- 9637880
TI - [Comparison of disease-free survival between bone marrow transplantation (BMT)
from unrelated donor and BMT from HLA identical sibling].
PMID- 9637881
TI - [Current status of allogeneic-peripheral blood stem cell transplantation and the
possibility for unrelated donor-peripheral blood stem cell transplantation].
PMID- 9637882
TI - [Future problems in cord blood transplantation].
PMID- 9637883
TI - [New strategies and future direction in hematopoietic stem cell transplantation
from unrelated volunteer donor].
PMID- 9637884
TI - [A pharmacokinetic study of the value of oral cytarabine ocfosfate in the
treatment of hematological malignancies].
AB - Cytarabune ocfosfate (SPAC) is rapidly transformed into cytarabine (ara-C) when
orally administered. The pharmacokinetics of SPAC was studied in six patients
with acute non-lymphocytic leukemia (ANLL) and/or myelodysplastic syndromes (MDS)
after oral administration of SPAC at 100 to 400 mg/day for 14 days. Plasma ara-C
concentrations reached a plateau in 48 to 96 hours after initiation of SPAC
administration, remained at this or a little higher level until one day after its
termination and were less than 1 ng/ml 8 days after the termination. From all of
pharmacokinetic data, the oral administration of SPAC at 150 to 300 mg/m2/day was
pharmacokinetically concluded to be comparable to the continuous infusion of ara
C at 20 mg/m2/day. All of the patients could receive SPAC for 14 days. SPAC is
considered to be useful for consolidation or maintenance chemotherapy of ANLL or
MDS outpatients who are unable to undergo intensive chemotherapy.
PMID- 9637885
TI - [Peripheral blood stem cell transplants: clinical considerations and observations
in practice in a general hospital].
AB - Of 36 patients with malignant tumors who had been subjected to peripheral blood
stem cell harvests (PBSCHs), 22 had undergone peripheral blood stem cell
transplants (PBSCTs) since 1993. Flow cytometry recorded higher CD34+ cell yields
in the PBSCHs of those patients with high white blood cell (WBC) counts as well
as those who had been under intensive chemotherapy. Also, higher CD34+ cell
yields were recorded in patients whose peripheral blood WBCs recovered more
rapidly from their nadir state. WBC counts recovered rapidly in patients who
received transfusions of at least 2.0 x 10(6) CD34+ cells/kg. However, patients
with acute non-lymphocytic leukemia (ANLL) demonstrated a delayed recovery in
their platelet counts following PBSCT. The mean disease-free survival rate and
mean disease-free period were 60% and 12.8 months for the 5 patients with ANLL;
and 100% and 11.3 months for the 4 patients with acute lymphocytic leukemia.
These findings suggest PBSCT is a safe and effective treatment for patients with
malignant tumors following high-dose chemotherapy, and can be performed in a
private general hospital.
PMID- 9637886
TI - [All-trans retinoic acid was effective for marked skin infiltration in a relapsed
acute myelogenous leukemia (AML-M2) patient with t(12; 17)].
AB - A 64-year-old man who had taken acute myelogenous leukemia (AML-M2) in 1989 have
relapsed with t(12; 17) (p13; q11.2-21) chromosomal abnormality and presenting
marked infiltration to the skin in 1994. Blasts were seen on his peripheral blood
smear (15%) and bone marrow examination showed increased leukemic cells (56%),
with maturation. Leukemic cells expressed CD13 and CD33 antigen but not HLA-DR.
Although leukemic cells had not promyelocytic feature morphologically, detection
of PML/RAR alpha infusion signal of peripheral leukemic cells were positive for
8% (1% for control) by fluorescence in situ hybridization method. Because he did
not response to standard combination chemotherapy and because we considered the
possibility that t(12; 17) (p13; q11.2-21) observed in this case are t(15; 17)
variant, we tried all trans retinoic acid (ATRA) to him. Interestingly, ATRA was
very effective for skin lesion but hematologically it had no effect at all, and
he died because of bacterial pneumonia.
PMID- 9637887
TI - [Successful double peripheral blood stem cell transplantation for patient with
malignant lymphoma of primary induction failure].
AB - Three patients with non-Hodgkin's lymphoma of intermediate-grade histologies, who
had failed to achieve a complete remission (CR) after more than several courses
of conventional chemotherapy were treated with two cycles of high-dose
chemotherapy with autologous peripheral blood stem cell transplantation (double
PBSCT). All patients received regimen A with carboplatin 1g/m2, etoposide 1.2g/m2
and cyclophosphamide 120mg/kg prior to 1st PBSCT and obtained a partial
remission. One patients received regimen A and two patients received regimen B
with MCNU 500mg/m2, etoposide 750mg/m2 and L-PAM 140mg/m2 prior to 2nd PBSCT and
all patients obtained CR. Second PBSCT was performed 3 to 5 months after the 1st
PBSCT. At a median follow-up of 36 (range; 29 to 54) months, all patients
remained in continuous CR. The period after reinfusion of PBSCT to achieve a
neutrophil count more than 500/microliters ranged between 7 and 9 days and to
achieve a platelet count more than 5 x 10(4)/microliters ranged 12 and 22 days.
Grade 3 nonhematologic toxicity (mucositis) was seen in one patient after 2nd
PBSCT. Double PBSCT could be well tolerated with a high response rate in patients
with malignant lymphoma of primary induction failure.
PMID- 9637888
TI - [Hemostatic evaluation of a patient with haloperidol-induced neuroleptic
malignant syndrome associated with disseminated intravascular coagulation].
AB - A 94-year-old man who had been admitted to our hospital for the treatment of
senile dementia and restless behavior exhibited consciousness disturbances, acute
respiratory failure, high fever, and thrombocytopenia the day after receiving
haloperidol as prescribed by a psychiatrist. On the fourth day following
administration of haloperidol, acute renal failure with rhabdomyolysis and
disseminated intravascular coagulation (DIC) developed in the patient, who was
accordingly given a diagnosis of haloperidol-induced neuroleptic malignant
syndrome (NMS) associated with DIC. He was then given heparin and antithrombin
III, and his DIC symptoms improved soon thereafter. Elevated plasma levels of
tissue factor and tumor necrosis factor-alpha (TNF-alpha) were sustained during
this therapy course. Other cytokines, including interleukin IL-1 beta, IL-2 and
IL-6, were not elevated. There are activation of extrinsic coagulation and an
elevated level of TNF-alpha during acute renal failure and rhabdomyolysis
associated with NMS, which is thought to trigger the onset of DIC.
PMID- 9637889
TI - [A fatal case of aggressive-phase multiple myeloma with ileus and invasion into
extramedullary organs].
AB - A 62-year-old woman with IgA-lambda type monoclonal gammopathy had been followed
up since January 1988. In March 1991, multiple myeloma (IgA-lambda) was diagnosed
on the basis of bone marrow biopsy findings and increased serum IgA levels. She
was treated intermittently with melphalan and prednisolone over a perioa of about
6 years, but was eventually admitted due to renal dysfunction, hypercalcemia,
increased serum IgA and the formation of subcutaneous masses. During chemotherapy
she underwent emergency surgery for obturative ileus. Histological examination of
the resected tissues revealed invasion of myeloma cells into the small intestine
and peritoneum. Despite continued chemotherapy, the patient's soft tissue masses
enlarged, and new lesions appeared in other organs. In the terminal stage, lower
serum IgA levels were observed despite an increase in Bence-Jones protein levels
in urine. The patient died five months after admission. An autopsy found
infiltration by atypical myeloma cells in multiple organs. An immunohistochemical
examination revealed and increase in lambda-light chain positive cells relative
to the number of alpha-heavy chain positive cells. The terminal course was
considered to be representative of aggressive phase multiple myeloma. The case
was rare in that the patient's ileus was caused by invasion of myeloma cells into
the small intestine.
PMID- 9637890
TI - [Hereditary spherocytosis associated with severe hypophosphatemia in patients
recovering from aplastic crisis].
AB - This is a report about two cases of hereditary spherocytosis complicated by
severe hypophosphatemia, while recovering from aplastic crisis. Case #1: A 31
year-old male, who had jaundice and splenomegaly since the age of 15 and who has
a son diagnosed with hemolytic anemia, was admitted because of fever
lymphadenopathy, and jaundice. A diagnosis of hereditary spherocytosis was made
based on microspherocytes observed in his peripheral blood smear. After
admission, the anemia became more serious for a few days and he was considered
suffering from bone marrow aplastic crisis. His serum phosphorus level fell to
0.5 mg/dl on the second day, but it rapidly returned to normal as reticulocyte
counts rose. Case #2: A 29-year-old male with known transient jaundice and
splenomegaly suffered from fever, anemia and jaundice, but recovered two weeks
later. Laboratory examination revealed positive human Parvovirus B19 (HPV-B19)
DNA, anti-HPV-19 IgM and IgG-antibody. His serum phosphorus level fell to 1.2
mg/dl on the eighth day, but it rose in the same manner as seen in case #1. The
fall in serum phosphorus is probably due to its shift to the erythroblasts during
erythroid hyperplasia.
PMID- 9637891
TI - [Hemophagocytic syndrome due to miliary tuberculosis in the course of aplastic
anemia].
AB - We report a 63 year-old female with aplastic anemia (AA) who was complicated with
hemophagocytic syndrome induced by systemic miliary tuberculosis. Two years
before admission to our hospital, she was diagnosed as AA and had been treated
with granulocyte colony-stimulating factor, erythropoietin and methenolone
acetate. In May, 1996, She was transferred to our hospital because of high fever
and exacervation of pancytopenia. She showed severe pancytopenia, and an increase
in macrophages showing remarkable erythrophagocytosis and decrease in hemopoietic
cells in the bone marrow. In initial examination, high titer of IgM antibody to
herpes simplex virus type I was identified and methylprednisolone pulse therapy
was started under the diagnosis of virus associated hemophagocytic syndrome. Ten
days later, however, she died for intestinal hemorrhage followed by multiorgan
failure. In autopsy, multiple epitheloid cell granulomas with acid-fast bacilli
were found in bone marrow, lungs, liver, spleen and kidneys.
PMID- 9637892
TI - [Acute myelogenous leukemia with hyperkalemia induced by pentamidine
administration].
AB - A 27-year-old male with acute myelogenous leukemia received an allogeneic bone
marrow transplantation (allo-BMT). Pneumocystis carinii pneumonia developed on
day 65 after the allo-BMT. The patient was intravenously treated with
pentamidine. This resulted in a prompt improvement of his dyspnea and fever, but
hyperkalemia occurred during the pentamidine therapy. Treatment with pentamidine
was stopped and emergent treatment was started. Nevertheless, the serum potassium
level rose to 7.7 mEq/l. Urgent dialysis was performed and the serum potassium
level fell to 5.0 mEq/l after treatment. Careful monitoring of the serum
potassium level is recommended during intravenous therapy with pentamidine.
PMID- 9637893
TI - [A retrospective study on the development of inhibitors in Japanese hemophiliacs
(second report, 1994 study). Research Group of Blood Products for Hemophilia
Inhibitor].
AB - In this report, we discuss the findings of a 1994 retrospective study concerning
the rate of inhibitor formation in Japanese hemophiliacs. The study was the
second of its kind, following on the first in 1991 (Kamiya et al. 1995 Int. J.
Hematology). The records of 77 medical institutions were examined. Inhibitors
were found in 6.50% (140 of 2154) of the patients with hemophilia A (HA), and
5.21% (22 of 422) of those with hemophilia B (HB). The median age for antibody
formation was 10.7 years in patients with HA, and 4.5 years in those with HB. The
median period (exposure period) from initial plasma factor concentrates exposure
to inhibitor formation was 46 days and 20 days, respectively, in the HA and HB
patients. Among the HA inhibitor patients, those with a large deletion or a
nonsense mutation were aged 17.4 years or less (0.58, 1.7, 3.5, 5.5, 7.0 and
17.4), whereas those with intron 22 inversion were aged 55.7 years or less (1.3,
1.3, 1.8, 33.0, 36.1, 37.7, 43.9, 47.9 and 55.7).
PMID- 9637894
TI - [Study on EEG patterns of schizophrenics--with use of FFT dipole approximation].
AB - EEG recording were performed in 22 non-treated schizophrenics; subsequently, the
combination of traditional EEG frequency analysis with FFT Dipole Approximation
as a new method for EEG analysis was employed to determine power spectra of
baseline EEGs and three dimensional model dipole source location in anterior
posterior, left-right and superior-inferior directions with changing the
frequency by 0.5 Hz. Quantitative EEG study included comparison of baseline EEGs
between normal volunteers and schizophrenics; the results obtained in this study
coincided with previous and reports in increase of slow wave, decrease of alpha
band and increase of fast wave. Dipole source location in schizophrenics were
generally shifted more towards superior and posterior areas compared with those
in normal volunteers whereas no shifts towards left-right areas were evidenced in
schizophrenics. Seven patients on monotherapy of haloperidol were subjected to
determination of dipole source location two weeks after commencement of the
medication. After treatment, the source locations shifted towards anterior and
inferior area, approaching to the dipole source locations in normal volunteers.
Baseline dipole source locations were negatively correlated with both positive
symptom rating score and negative symptom rating score according to BPRS,
indicating that with increasing positive symptom rating score, the source
location shifted towards posterior direction, and higher negative symptoms rating
scores were associated with a shift towards right direction. These findings
support our view that negative symptoms and positive symptoms might be associated
with frontal lobe dysfunction theory and temporal lobe dysfunction theory.
PMID- 9637895
TI - [Psychopathological study on "hallucination of soliloquy" in a case of
schizophrenia].
AB - We present what appears to be the first reported case of schizophrenia with
hallucinatory soliloquy. An appropriate name for this symptom might be
"hallucination of soliloquy." A thirty-year-old man had been laboring under
delusions of persecution and auditory hallucinations in the form of being blamed
by others after changing his job at the age of twenty-eight. He consulted our
hospital because of unintentional "soliloquy." He complained that he had been
maltreated in his new work place and that this stress made him talk to himself.
The contents of his "soliloquies" were nonsensical; for example, he would grumble
about his colleagues or the plot of a teleplay that he had seen the previous day.
During his "soliloquies" he had the vivid sensation of both speaking and hearing
his own voice, but the episodes actually lacked vocalization. As a result of
therapy, the patient's disorder gradually shifted from "soliloquy" to "silent
soliloquy," then to "breathing hard," before finally disappearing. We are aware
of a similar symptom, "delusion of soliloquy" (Y. Kasahara et al.), in which the
patient believes that he unintentionally spoke to himself and that everyone
learned his secrets through his soliloquy. In comparison, our "hallucination of
soliloquy" is unique in that it is an abnormal experience of both speaking and
hearing. From the viewpoint of traditional symptomatology, "hallucination of
soliloquy" is composed of auditory hallucinations, which are experiences of
hearing, and psychomotor hallucinations, which are experiences of speaking. In
other words, it is a simultaneous experience of both thought resonance and
"hallucination verbale psychomotrice" (J. Seglas) or "Halluzination des
Muskelsinns" (A. Cramer) of the speech apparatus. However the overall concept of
"hallucination of soliloquy" deviates from both thought resonance and
"hallucination verbale psychomotrice" or "Halluzination des Muskelsinns." For a
different point of view, we refer to L.S. Vygotsky's studies on inner speech. A
comparison of "hallucination of soliloquy" with inner speech suggests that
"hallucination of soliloquy" is "inner speech which is converted into outer
speech" or "egocentric speech without vocalization." S. Kato notes that two
patterns are found in the schizophrenic discourse, mirroring discourse and
deviant discourse, which are named after mirroring and deviant characters
concerning the ordinary linguistic code. The former simulates the ordinary
linguistic code. In mirroring discourse, the patient almost literally imitates
and repeats customary discourse such as an authority's speech or television. The
latter is characterized by deviation from human actuality or the existing
linguistic code and is represented by delusions, neologisms, and incoherent
speeches. It has been suggested that mirroring discourse has moments of return to
actuality, while in deviant discourse the patient remains entirely in the
delusional world. It is said that discourse is realized in the deviant mode in
the case of ordinary auditory hallucinations. In the case of "hallucination of
soliloquy," the discourse occurs in the patient's own mind and is spoken through
his own mouth, in short, it is realized in mirroring mode. We conclude that
"hallucination of soliloquy" has the characteristic of mirroring discourse, which
is realized in mirroring mode. We suggest that "hallucination of soliloquy" is
schizophrenic auditory hallucination that has self-healing moments.
PMID- 9637896
TI - The Web, communication trends, and children's health. Part 4: How children use
the Web.
AB - Children are embracing the Internet and the World Wide Web. How are they using it
and what do they find? This article, the fourth in a five-part series, explores
the "whys" and the "wherefores" of children's Web use. Included are online
recourses geared specifically for children, including health, educational, and
entertainment sites.
PMID- 9637897
TI - Randomized, single-blinded comparative study of the efficacy of amoxicillin (40
mg/kg/day) versus standard-dose penicillin V in the treatment of group A
streptococcal pharyngitis in children.
AB - A 10-day course of amoxicillin at a dosage of 40 mg per kilogram per day was
compared with conventional (lower dosage) penicillin V therapy in the treatment
of culture-proven Group A streptococcal pharyngitis in children 3 to 18 years of
age in a prospective, randomized, and single-blinded study. Children had to have
signs and symptoms compatible with the diagnosis of streptococcal pharyngitis and
to have a throat swab positive for Group A streptococci. A second throat culture
was obtained 10 to 14 days after the completion of therapy. Serotyping was
performed to help differentiate carrier states from reinfections. Of 161 children
enrolled, 113 were evaluable; 55 received penicillin and 58 received amoxicillin.
At the completion of therapy 70.9% (39/55) of patients in the penicillin group vs
87.9% (51/58) of patients in the amoxicillin group were asymptomatic (clinical
cure, P = 0.025). At the completion of therapy, 54.5% (30/55) of patients in the
penicillin group vs 79.3% (46/58) of patients in the amoxicillin group had
negative throat cultures (bacteriologic cure, P = 0.005). The carrier rate
(children who were well but who were still carrying the same serotype of Group A
streptococcus) also differed between the groups: 13 (23.6%) in the penicillin
group compared with six (10.3%) in the amoxicillin group. Amoxicillin at 40
mg/kg/day was significantly more effective than lower dosages of penicillin V for
clinical and bacteriologic cure in the treatment of Group A streptococcal
pharyngitis in children. The current perception that penicillin is declining in
effectiveness may be due to inadequate dosing.
PMID- 9637898
TI - Hypophosphatemia in malnourished children during refeeding.
AB - Hypophosphatemia in malnourished children during nutritional recovery (refeeding
hypophosphatemia) is recognized as a cause of morbidity and mortality in
adolescents with anorexia nervosa but has been only rarely reported to occur in
younger children with other diagnoses. Over a 6-year period, we encountered three
cases of refeeding hypophosphatemia in malnourished children admitted to a
pediatric rehabilitation hospital. Two children had neurologic dysphagia and one
had been starved by an abusive parent. The one patient who was symptomatic had
obtundation, hemolytic anemia, rhabdomyolysis, and hepatocellular injury that
began during refeeding and resolved with treatment. The signs and symptoms,
pathophysiology, and treatment of refeeding hypophosphatemia are reviewed.
PMID- 9637899
TI - Earlier discharge of infants from neonatal intensive care units: a pilot program
of specialized case management and home care. Delaware Valley Child Health
Alliance.
AB - A multidisciplinary approach using a neonatology independent physicians
association, affiliated hospitals, a pediatric home care company, and a health
maintenance organization was designed to promote earlier safe discharge of
infants from intensive care. This pilot project involved 43 infants who received
case management and early discharge home with home oxygen, monitoring,
intravenous antibiotics, gavage feedings, phototherapy, or nutritional management
for poor weight gain. A staff neonatologist remained the primary physician until
the patient would have been discharged according to standard criteria. Two
patients had unscheduled readmissions and all infants survived. This approach
resulted in an estimated savings of 456 hospital days and $329,982; 89% of
parents rated the care as good to excellent, and 83% were satisfied with the
program and outcome. This study suggests that a prospectively designed program
can be designed to promote safe earlier discharge of infants in intensive care.
PMID- 9637900
TI - Pitfalls in the diagnosis of aerodigestive tract foreign bodies.
AB - In the young child, particularly those between the ages of 1 and 3 years,
aerodigestive tract foreign bodies continue to be a significant problem. Early
diagnosis and treatment can decrease morbidity and length of hospital stay in
these children. Three cases of delayed diagnosis in children with bronchial (2)
and esophageal (1) foreign bodies are presented. In dealing with young children
it is important to maintain a high clinical suspicion of a foreign body and to
perform a detailed history and physical examination. Options in radiographic
analysis of the patient with a suspected foreign body, probable locations of the
foreign body, and the likelihood of definitive radiographic findings are
discussed. Importantly, a negative radiographic analysis does not rule out the
presence of an aerodigestive tract foreign body. Two flow charts for the
evaluation of patients who have possibly ingested or inhaled a foreign body are
presented to aid the primary care physician in diagnosis.
PMID- 9637901
TI - Evaluation of boys with marked breast development at puberty.
AB - During the 10-year period from 1979 to 1988 we evaluated 60 boys who were more
than 9 years old and who had significant breast development (greater than 4 cm in
diameter) around the time of puberty. An endocrine abnormality was identified in
seven subjects. The pathology included Klinefelter's syndrome; 46,XX maleness;
primary testicular failure; partial androgen insensitivity; fibrolamellar
hepatocarcinoma; and increased aromatase activity. Eight of the remaining 53
subjects had underlying medical problems, five of them having neurologic
disorders. The 45 remaining subjects were considered to have significant
idiopathic gynecomastia, a condition sometimes referred to as macromastia. These
boys tended to be both taller and heavier than average, the mean Z score for
height being 1.4 SDs above the mean and the mean weight score being 2.7 SDs above
the mean. This study underscores the observation that pathologic causes of marked
pubertal gynecomastia are unusual. However, the potential for significant health
problems among boys with marked breast development supports the need for an
endocrine evaluation of all affected subjects. Our data also indicate that boys
with marked idiopathic breast development have greater body mass than other boys
of similar age. This may contribute in part to the greater breast development in
these subjects.
PMID- 9637903
TI - An unusual source of lead poisoning.
PMID- 9637904
TI - Long-term prognosis of acute renal failure in the full-term neonate.
PMID- 9637902
TI - Deep venous thrombosis in a preterm newborn of a mother with activated protein C
resistance.
PMID- 9637905
TI - Neonatal acute renal failure: the need for long-term follow-up.
PMID- 9637906
TI - Head lice therapy revisited.
PMID- 9637907
TI - "Anti-cancer gene found".
PMID- 9637908
TI - The Frizzled CRD domain is conserved in diverse proteins including several
receptor tyrosine kinases.
PMID- 9637909
TI - The Wnt receptor CRD domain is also found in MuSK and related orphan receptor
tyrosine kinases.
PMID- 9637910
TI - Bacterial motility: secretory secrets of gliding bacteria.
AB - Many bacteria glide over surfaces without the aid of flagella. Gliding is still
somewhat mysterious, but recent studies show that it involves specialized
secretory systems that assemble membrane-associated filaments, and the
recognition of extracellular components that trigger movement via transmembrane
transducers.
PMID- 9637911
TI - Neurophysiology: electrically evoking sensory experience.
AB - Monkeys trained to distinguish touch stimuli that 'flutter' with different
frequencies can similarly distinguish electrical stimulation of the somatosensory
cortex according to its frequency; the implication is that the electrically
evoked patterns of cortical activity cause flutter sensations similar to those
induced by touch.
PMID- 9637912
TI - Organogenesis: Drosophila goes gonadal.
AB - In many animals, germ cells migrate to the gonad to assemble into a functional
organ. Recent work in Drosophila has built a picture of the gene activities that
specify the gonad and allow it to attract germ cells, and has led to the
identification of a gene, columbus, that may encode the attractive factor.
PMID- 9637913
TI - Anti-apoptosis therapy: a way of treating neural degeneration?
AB - Many degenerative diseases involve apoptotic cell death--can they be treated with
apoptosis inhibitors, while protecting the normal physiological function of the
rescued cells? Reason for optimism comes from a recent study of mutant flies with
an analogue of the human degenerative disease retinitis pigmentosa.
PMID- 9637914
TI - Transcription: gene control by targeted histone acetylation.
AB - A transcriptional regulator in yeast, Gcn5p, activates transcription by targeted
acetylation of specific lysine residues in the amino-terminal tails of histones.
This targeted modification is restricted to nucleosomes assembled on the
promoters of Gcn5p-responsive genes.
PMID- 9637915
TI - Mechanosensation: swimming round in circles.
AB - Studies of inherited deafness disorders in mice and humans are providing new
insights into the basis of hair-cell mechanosensitivity; this enterprise has been
joined by large-scale genetic screening in the zebrafish, where a number of
intriguing mutants defective in mechanosensation have recently been described.
PMID- 9637916
TI - Prostate cancer: new therapies in the pipeline?
AB - Cancer of the prostate gland is the highest unavoidable cause of cancer mortality
in men. The recent identification and characterisation of genes specifically
expressed in prostate cancer helps us to understand its molecular basis and
should offer new therapeutic avenues to combat this disease.
PMID- 9637917
TI - Olfactory G proteins: simple and complex signal transduction.
AB - In both vertebrates and invertebrates, olfactory perception is mediated by G
protein-coupled receptors. Recent work, in both mouse and Caenorhabditis elegans,
sheds light on the role of specific G proteins in olfactory signal transduction,
neuronal morphology and axon guidance.
PMID- 9637918
TI - Identification of the basolateral targeting determinant of a peripheral membrane
protein, MacMARCKS, in polarized cells.
AB - BACKGROUND: Although the molecular determinants that specify the targeting of
transmembrane proteins to the apical or basolateral membrane domains within
polarized epithelial cells have been well characterized, very little is known
about the targeting of peripheral membrane proteins within these cells. MacMARCKS
is a member of the MARCKS family of protein kinase C (PKC) substrates. This
myristoylated protein regulates actin structure at cell membranes and is
essential for the morphogenic movement of neuroepithelial cells during the
formation of the neural tube. RESULTS: MacMARCKS was specifically targeted to
sites of cell-cell contact in the basolateral domain of polarized Madin-Darby
canine kidney (MDCK) epithelial cells and was displaced from this location upon
activation of PKC. We defined the basolateral targeting determinant of MacMARCKS
to be the effector domain, a basic region spanning 24 amino acids and containing
the PKC phosphorylation sites as well as binding sites for calmodulin and actin.
This domain, in conjunction with a myristoyl moiety, was sufficient to target a
non-membrane-associated protein--green fluorescent protein--specifically to the
basolateral surface of polarized MDCK cells. CONCLUSIONS: This is the first
description of a specific amino acid sequence that specifies targeting of a
peripheral membrane protein to the basolateral membrane in polarized epithelial
cells.
PMID- 9637919
TI - Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to
activate protein kinase B.
AB - BACKGROUND: Protein kinase B (PKB) is involved in the regulation of apoptosis,
protein synthesis and glycogen metabolism in mammalian cells. Phosphoinositide
dependent protein kinase (PDK-1) activates PKB in a manner dependent on
phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), which is also needed
for the translocation of PKB to the plasma membrane. It has been proposed that
the amount of PKB activated is determined exclusively as a result of its
translocation, and that a constitutively active pool of membrane-associated PDK-1
simply phosphorylates all the PKB made available. Here, we have investigated the
effects of membrane localisation of PDK-1 on PKB activation. RESULTS: Ectopically
expressed PDK-1 translocated to the plasma membrane in response to platelet
derived growth factor (PDGF) and translocation was sensitive to wortmannin, an
inhibitor of phosphoinositide 3-kinase. Translocation of PDK-1 also occurred upon
its co-expression with constitutively active phosphoinositide 3-kinase, but not
with an inactive form. Overexpression of PDK-1 enhanced the ability of PDGF to
activate PKB. PDK-1 disrupted in the pleckstrin homology (PH) domain which did
not translocate to the membrane did not increase PKB activity in response to
PDGF, whereas membrane-targeted PDK-1 activated PKB to the extent that it could
not be activated further by PDGF. CONCLUSIONS: In response to PDGF, binding of
Ptdlns (3,4,5)P3 and/or Ptdlns(3,4)P2 to the PH domain of PDK-1 causes its
translocation to the plasma membrane where it co-localises with PKB,
significantly contributing to the scale of PKB activation.
PMID- 9637920
TI - Imaging the spatial dynamics of calmodulin activation during mitosis.
AB - BACKGROUND: Calcium is an important and ubiquitous signalling ion. In most cell
types, changes in intracellular calcium concentrations are sensed by calmodulin,
a signal transduction protein that regulates cell function through its
interactions with kinases and phosphatases. Calcium signals show complex
spatiotemporal patterning, but little, if anything, is known about the patterns
of calmodulin activation inside cells. RESULTS: We have measured calmodulin
activation continuously during mitosis in living cells with a new probe, a
fluorescent adduct of calmodulin termed TA-calmodulin. We found that calmodulin
was activated locally and episodically in the nucleus and mitotic spindle. The
pattern of calmodulin activation was different from the pattern of calcium
signals and could not be predicted from the pattern of calcium increase.
Calmodulin activation was essential for mitotic progression: both entry into
mitosis and exit from mitosis were blocked by a novel peptide that bound to
calmodulin with high affinity and so prevented the interaction of calmodulin with
its target proteins. CONCLUSIONS: These data suggest that calmodulin regulates
mitotic transitions and demonstrate the utility of fluorescent adducts for
studying protein activation in living cells with good temporal and spatial
resolution.
PMID- 9637921
TI - Thymic skewing of the CD4/CD8 ratio maps with the T-cell receptor alpha-chain
locus.
AB - The thymic preference for CD4+ T cells over CD8+ T cells is often attributed to a
default pathway favouring CD4+ T cells or to homeostatic mechanisms. It is also
clear, however, that T-cell receptor (TCR) preferences for major
histocompatibility complex (MHC) class I versus class II binding will strongly
influence an individual clone's skewing to the CD4 or CD8 subset. The variable
region of each TCR alpha chain (V alpha) studied to date is found to be
overrepresented in either CD4+ or CD8+ cells, suggesting that each V alpha
element can interact more favourably with either MHC class I or class II
molecules. Indeed, TCRs appear to have an intrinsic ability to interact with MHC
molecules, and single amino acid residues present in germline-encoded
complementarity determining region 1 (CDR1) and CDR2 of the V alpha element can
be responsible for determining MHC specificity. Interestingly, the degree of
CD4/CD8 skewing is variable among different mouse strains and in human
populations. Here, we have shown that polymorphism in CD4/CD8 skewing between B6
and BALB/c mice is determined by the stem cell genotype and not by environmental
effects, and that it maps in or near the TCR alpha-chain complex, Tcra. This was
confirmed by comparing Tcra(b) with Tcra(a) or Tcra(c) haplotypes in congenic
mice. We propose that the array of V alpha genes in various Tcra haplotypes
exerts influence over the proportion of CD4 and CD8 subsets generated and may
account in part for the observed thymic skewing. Thus, while it has been
suggested that the TCR genes have been selected by evolution for MHC binding, our
results further indicate selection for class II MHC preference.
PMID- 9637922
TI - Identification and functional analysis of the ezrin-binding site in the
hyaluronan receptor, CD44.
AB - ERM (ezrin, radixin and moesin) proteins function as linkers between the actin
cytoskeleton and the plasma membrane. In addition to this structural role, these
proteins are highly regulatable making them ideal candidates to mediate important
physiological events such as adhesion and membrane morphology and to control
formation and breakdown of membrane-cytoskeletal junctions. Recently, a direct
interaction in vitro has been demonstrated between ERM proteins and the
hyaluronan receptor, CD44. We have mapped the ezrin-binding site to two clusters
of basic amino acids in a membrane-proximal 9 amino-acid region within the CD44
cytoplasmic domain. To investigate the functional importance of this interaction
in vivo, we created a number of mutations within full-length CD44 and expressed
these mutants in human melanoma cells. We demonstrate here that mutations within
the ezrin-binding site do not disrupt the plasma membrane localization of CD44
and, in addition, that this region is not required to mediate efficient
hyaluronan binding. These studies suggest that ERM proteins mediate the outside
in, rather than inside-out, signalling of adhesion receptors.
PMID- 9637923
TI - The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading
complex.
AB - The proper folding and assembly of major histocompatibility complex (MHC) class I
molecules in the endoplasmic reticulum (ER) is an intricate process involving a
number of components. Nascent heavy chains of MHC class I molecules, translocated
into the ER membrane, are rapidly glycosylated and bind the transmembrane
chaperone calnexin. In humans, after dissociation from calnexin, fully oxidized
MHC class I heavy chains associate with beta 2-microglobulin (beta 2m) and the
soluble chaperone calreticulin. This complex interacts with another transmembrane
protein, tapasin, which is believed to assist in MHC class I folding as well as
in mediating the interaction between assembling MHC class I molecules and the
transporter associated with antigen processing (TAP). The TAP heterodimer (TAP1
TAP2) introduces the final component of the MHC class I molecule by translocating
peptides, predominately generated by the proteasome, from the cytosol into the ER
where they can bind dimers of beta 2M and the MHC class I heavy chain. Recently,
the thiol oxidoreductase ERp57--also known as GRP58, ERp61, ER60, Q2, HIP-70, and
CPT and first misidentified as phospholipase C-alpha--has been shown to bind in
conjunction with calnexin or calreticulin to a number of newly synthesized ER
glycoproteins when their N-linked glycans are trimmed by glucosidases I and II.
It was speculated that ERp57 is a generic component of the glycan-dependent ER
quality control system. Here, we show that ERp57 is a component of the MHC class
I peptide-loading complex. ERp57 might influence the folding of MHC class I
molecules at a critical step in peptide loading.
PMID- 9637924
TI - A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I
molecules.
AB - An important mammalian defence strategy against intracellular pathogens is the
presentation of cytoplasmically derived short peptides by major
histocompatibility complex (MHC) class I molecules to cytotoxic T lymphocytes.
MHC class I molecules assemble in the endoplasmic reticulum (ER) with chaperones,
including calnexin and calreticulin, before binding to the transporter associated
with antigen processing (TAP). We show here that the thiol-dependent reductase
ERp57 (also known as ER60 protease) is involved in MHC class I assembly. ERp57 co
purified with the rat TAP complex (comprising TAP1 and TAP2), and associated with
MHC class I molecules at an early stage in their biosynthesis. This association
was sensitive to castanospermine, which inhibits the processing of glycoproteins.
Human MHC class I molecules were also found to associate with ERp57. We conclude
that ERp57 is a newly identified component of the MHC class I pathway, and that
it appears to interact with MHC class I molecules before they associate with TAP.
PMID- 9637925
TI - Evidence for successive peptide binding and quality control stages during MHC
class I assembly.
AB - Intracellular antigens are continually presented to cytotoxic T lymphocytes by
major histocompatibility complex (MHC) class I molecules, which consist of a
polymorphic 43 kDa heavy chain and a 12 kDa soluble subunit beta 2-microglobulin
(beta 2m), and which bind an 8-10 amino-acid antigenic peptide. The assembly of
this trimolecular complex takes place in the lumen of the endoplasmic reticulum
(ER) and almost certainly requires cofactors. Most MHC class I molecules in the
ER that have not yet acquired peptide are simultaneously bound to the transporter
associated with antigen processing (TAP), to the 48 kDa glycoprotein tapasin and
to the lectin-like chaperone calreticulin, in a multicomponent 'loading complex'.
Previous studies have shown that a mutant MHC class I molecule T134K (in which
Thr134 was changed to Lys) fails to bind to TAP. Here, we show that this point
mutation also disrupted, directly or indirectly, the interaction between MHC
class I molecules and calreticulin. T134K molecules did not present viral
antigens to T cells even though they bound peptide and beta 2m normally in vitro.
They exited the ER rapidly as 'empty' MHC class I complexes, unlike empty wild
type molecules which are retained in the ER and degraded. We show here that,
paradoxically, the rapid exit of empty T134K molecules from the ER was dependent
on a TAP-derived supply of peptides. This implies that MHC class I assembly is a
two-stage process: initial binding of suboptimal peptides is followed by peptide
optimisation that depends on temporary ER retention.
PMID- 9637926
TI - EGF induces recycling membrane to form ruffles.
AB - KB cells are know to respond to epidermal growth factor (EGF) by producing
prodigious ruffles in the plasma membrane within minutes. The signal transduction
pathway underlying this effect in fibroblasts is mediated through Rac, a member
of the Ras-like family of GTPases. As ruffles are rich in components of the
cytoskeleton--particularly in actin and ezrin--it has been suggested that ruffles
arise when activated Rac modulates the actin cytoskeleton to push out a membrane
protrusion. We set out to see whether the surface of new ruffles arises from
neighbouring membrane, or whether it comes from an intracellular pool of
endocytosed membrane. If it arose by exocytosis from endosomes, it would be
expected to be enriched in those recycling receptors that are concentrated in
coated pits in the endocytic side of the cycle. On the other hand, if it arose
passively from the adjacent plasma membrane, a uniform distribution of these
receptors would be expected. Here, we show that as soon as ruffles appear on KB
cells in response to EGF, their membrane surfaces are enriched in both
transferrin and low density lipoprotein (LDL) receptors. Both these proteins are
known to be selectively concentrated into endosomal membranes by clathrin
mediated endocytosis. Our results reveal that the surfaces of ruffles arise by
exocytosis of internal membrane from the endocytic cycle and, therefore, that a
primary action of Rac is to redirect the exocytosis of recycling membrane into
just those specific sites where ruffles form.
PMID- 9637927
TI - Formation of RuvABC-Holliday junction complexes in vitro.
AB - In Escherichia coli, the RuvA, RuvB and RuvC proteins are required for the late
stages of homologous recombination and DNA repair. RuvA and RuvB form a complex
that interacts with Holliday junctions--crossed DNA structures that are
recombination intermediates--and promotes branch migration; RuvC is a junction
specific endonuclease that resolves Holliday junctions and completes the
recombination process. Because genetic and biochemical experiments suggest that
the processes of branch migration and resolution are linked,
coimmunoprecipitation experiments were carried out to determine whether the three
Ruv proteins interact to form a functional complex (RuvABC). Using a synthetic
Holliday junction, a multisubunit complex containing the junction and RuvA, RuvB
and RuvC was detected. In the absence of RuvB, RuvAC-junction complexes were
observed. Complex formation was not facilitated by duplex DNA. The identification
of a RuvABC-junction complex provides direct evidence that the RuvABC proteins
interact at the Holliday junction.
PMID- 9637928
TI - Genetic advances in cystic fibrosis: to screen, to treat or both?
AB - Since the identification of the cystic fibrosis (CF) gene in 1989 there have been
considerable advances in treatment and fierce debate concerning CF screening
programmes. Cystic fibrosis imposes a burden of suffering, of onerous treatment
and of reduced lifespan. New emerging treatments are very expensive but are
expected to improve survival and quality of life. Treatments and screening
programmes should not be played off against one another in choices for funding.
This paper presents an argument for the appropriate use of newer treatments which
could be funded from savings arising from the effects of widespread
implementation of newborn and active cascade carrier detection programmes.
Newborn screening delays the need for expensive treatments reserved for those
with advanced disease, by reducing pre-diagnosis tissue damage and the rate of
progression of the disease. Carrier screening has the capacity to decrease the
numerical burden of affected children born and increases the number of children
born free of disease. For the present, carrier screening in the absence of a
family history could be funded by the individuals who wish it or by those
prepared to buy this service. All types of screening presume quality control, an
existing laboratory and counselling infrastructure and an established method of
communicating results.
PMID- 9637929
TI - Transition from paediatric to adult-orientated care for adolescents with cystic
fibrosis.
AB - Adolescence is a time of major physical and psychological change. Young teenagers
need to become comfortable with their developing sexuality, to begin moving
towards independence with a greater reliance on peer group acceptance, to face
the future and to make important decisions about their education, career and
goals. Difficulties inherent in all of these steps to adult life are magnified by
chronic ill health. It is harder for adolescent patients to break family ties,
harder to feel accepted by their peer group, harder to plan realistically for the
future. It must be the overriding aim of the professional health carers to
encourage these patients to confront the problems of adolescence and to help them
maintain their physical and emotional stability throughout this challenging
period. Parents also must be supported, and encouraged gradually to devolve to
their child responsibilities for decision making and for taking prescribed
medication. A planned and sensitive transition from a paediatric to an adult
health-care system will aid a successful evolution to an independent adult life.
The paediatric hospital environment is not best equipped to deal with the
problems of adolescence. Just as parents must allow their child to move on, so
the paediatric caring team must loosen its ties with the patient and allow
transfer to the adult team. There are several ways of effecting this transfer of
care. None of them is proven to be better than any other, but the transfer should
always be planned, smooth, efficient and expected by the patient. Ideally, all
patients should have the opportunity to transfer to a properly equipped and
properly staffed adult cystic fibrosis centre where they can continue to receive
the highest standards of care from an experienced multidisciplinary team.
PMID- 9637930
TI - The management of young adults with cystic fibrosis: 'genes, jeans and genies'.
AB - Cystic fibrosis is now an adult disease. The understanding of the basic
pathophysiology of this disease has increased considerably over the past decade.
This has resulted in effective management protocols and the development of
innovative approaches to therapy. Management of young adults is complex and
requires expert medical care delivered in a sensitive and appropriate way. The
daily treatment schedule for many adults involves physiotherapy; nebulized, oral
and i.v. drugs; exercise and nutritional supplements. Adherence to such treatment
while living a busy school, work and social life is extremely difficult for
patients. The psychological implications of having a disease with very
significant morbidity and mortality also has an enormous impact on individuals
with CF. Many of these issues have evolved as survival has increased and the next
few decades may produce more unexpected 'genies'. These may be from the disease
itself or from some of the exciting new treatments currently being developed. It
is important that individuals with CF are fully involved in decisions relating to
their treatment and that CF teams provide optimal and appropriate care to enable
these young adults to enjoy their lives to the fullest extent.
PMID- 9637931
TI - Nutritional management in cystic fibrosis--an alternative perspective in
gastrointestinal function.
AB - The gastrointestinal problems in cystic fibrosis (CF) may limit energy and
nutrient availability and also cause symptoms such as abdominal pain and
disturbed bowel habit which may further suppress appetite or alter the diet.
Taken together this may lead to an inadequate supply of energy and nutrients to
meet the nutritional requirements of the individual resulting in restricted
growth or weight loss. A failure to optimize the digestive and absorptive
capacity of the gastrointestinal tract places greater emphasis upon nutritional
management by food intake alone. Practitioners need to focus more on
gastrointestinal dysfunction in CF and its impact upon food intake in order to
improve the efficacy of nutritional management. Refined stable isotopic tracers
allow further exploration of the pathophysiology of the gastrointestinal tract in
terms of nutrient availability. In clinical practice, a closer assessment of
gastrointestinal function is supported by the use of simple, noninvasive tools
which, both objectively and systematically, characterize those patients who have
problems.
PMID- 9637932
TI - Finding evidence to support airway clearance techniques in cystic fibrosis.
AB - Chest physiotherapy, aiming to clear bronchopulmonary secretions, has become a
mainstay in the respiratory management of cystic fibrosis (CF). Early diagnosis
and new therapeutic interventions have dramatically improved the outlook for
patients with this disorder and it is no longer a disease of childhood. Along
with these changes chest physiotherapy has also progressed, with the development
of several treatment modalities that are more effective and can be performed by
the patient without assistance. This allows older children and adults with CF to
lead more normal and independent lifestyles. Despite this progress questions
remain regarding the efficacy and consequences of airway clearance techniques,
the scientific evidence available to support the selection of the most
appropriate treatment modality and, not least, the problems associated with the
treatment-related burden that is placed on patients and their families.
PMID- 9637933
TI - Exercise limitations and training for patients with cystic fibrosis.
AB - Exercise has much to offer to cystic fibrosis patients. Overcoming the limits of
decreased pulmonary function by increasing fitness has a considerable potential
to improve patients' quality of life; decreased breathlessness allows greater
mobility and participation with peers in social and sporting activities, improves
confidence and self-esteem and creates a greater pleasure in life for the
individual patient. There are also immediate therapeutic gains and potentially
long-term gains with improved survival. Above all, cystic fibrosis patients enjoy
and prefer exercise as a therapeutic option to most other forms of therapy.
PMID- 9637934
TI - Community-based care in cystic fibrosis: role of the cystic fibrosis nurse
specialist and implications for patients and families.
AB - Improved survival for cystic fibrosis has rapidly increased over the past four
decades, with patients now living well into adult life. With changes in the
structure of the National Health Service and the formation of provider units and
general practitioner (GP) fund-holding practices, it is important to strengthen
links between the hospital and community teams to ensure that the CF patient
receives adequate care. Increasingly, treatment is being carried out at home, and
this emphasis on home-based therapy demands that parents/carers and patients must
acquire the skills and knowledge of complex therapies in order to optimize
health. It is the role of the CF nurse specialist (NS) to educate those who will
deliver the care, co-ordinate the provision of services at home, liaise with the
CF team and community health-care professionals and to support the patient and
their carers.
PMID- 9637935
TI - Contemporary psychosocial issues in cystic fibrosis: treatment adherence and
quality of life.
AB - This review focuses on the two major psychosocial areas currently topical in
cystic fibrosis research: treatment adherence and quality of life. First, the
paper discusses the importance of evaluating adherence to treatments and medical
advice, its measurement, predictors of adherence and non-adherence and whether
the data should be used to inform clinical practice and policy decisions. Second,
the purpose of evaluating quality of life in cystic fibrosis and an overview of
the data are discussed. Both areas have suffered from problems with terminology
and definition, inappropriate methodologies and hence difficulties with data
interpretation. Future directions for research are advocated.
PMID- 9637936
TI - It's not football.
AB - Today I am as happy as I could ever be. I have created a lot out of very little,
I have worked full time, played full time, got full-time friends, full-time
independence, had full-time love and am lucky enough to be with my new full-time
love who helps me a great deal both physically and mentally. It is definitely no
fun coughing until your chest is sore in the morning, afternoon and evening.
Having wringing night-sweats from cepacia. Wanting to sleep more than Mr Sleep
from Sleepland. Taking tablets the size of which sunk the Belgrano. Finding time
for physiotherapy, eating the right meals, playing on my Playstation. Depression
has got through on previous occasions, but not for long, and it has never
resulted in anything more than a 'wake up and smell the coffee' call from myself.
Having CF is no ball game (otherwise it would be called football or something!),
but I have had a lot of fun and will continue to do so for however long. Two
years, five years, 20 years--who's to say, not me. We could all have the same
left, I just hope that everyone has as much fun.
PMID- 9637937
TI - Neurophysiological study in an Italian family with autosomal dominant late-onset
leukodystrophy.
AB - Evoked potentials (EPs) and nerve conduction velocities (NCV) were evaluated in 8
affected and 10 asymptomatic members of a new Italian family with an adult-onset
autosomal dominant leukodystrophy of uncertain nosography. NCV studies did not
show anomalies. Various EPs abnormalities were found in all the symptomatic
patients (increase of interpeak latency and/or loss of cortical responses),
according with a myelin disorder. Among the asymptomatic subjects 3/10 (30%)
showed similar anomalies at auditory brainstem EPs (increase of I-III/I-V/III-V
interval). Two of these patients had normal brain MRI. This datum require further
confirms (very low penetrance of the disease?), but it remarks the importance of
a functional study of SNC in order to obtain elements not usually given from
clinical and neuroradiological study.
PMID- 9637938
TI - Cerebral potentials are not evoked by activation of Golgi tendon organ afferents
in human abductor hallucis muscle.
AB - The earliest components of the somatosensory evoked potentials (SSEP) are
generated by excitation of the fastest low-threshold, thick myelinated group I
afferents. Ib afferents belonging to this group innervate Golgi tendon organs and
are excited almost selectively by a muscle twitch. Contraction of the abductor
hallucis muscle was evoked by intramuscularly placed teflon insulated needle
electrodes in ten healthy volunteers. We failed to demonstrate any cortical
activity (over Cz' vs. Fz) following isolated muscle contractions. Our results do
not point to a significant projection of group Ib afferents to the human
somatosensory cortex at least with the small numbers of fibers activated by
intramuscular stimulation of abductor hallucis muscle.
PMID- 9637939
TI - Activation and suppression of the trapezius muscle induced by transcranial
magnetic stimulation.
AB - Motor evoked potentials (MEPs) and silent periods (SPs) in the trapezius muscle
induced by transcranial magnetic stimulation (TMS) were investigated in 15
healthy subjects. Stimuli were applied with a Novametrix Magnetic stimulator
using a 14 cm circular coil 4 cm lateral to the vertex on the biauricular line.
Surface electrodes were used for simultaneous bilateral electromyographic
recordings of the trapezius. TMS invariably induced contralateral MEPs (latency
10.5 +/- 1.3 ms, mean +/- SD), with ipsilateral responses in 53% of the subjects
(latency 11.1 +/- 2.5 ms). The mean duration of the SPs was approximately 90 ms
on both sides. There were no significant side differences between any of the MEP
or SP parameters. To study the influence of subcortical inhibition phenomena TMS
induced responses were assessed following electrical mental nerve stimulation
with interstimulus intervals (ISI) of 0-100 ms. MEP latencies significantly
increased at ISI of 10-100 ms, whereas MEP amplitudes and SPs did not change.
These findings may reflect a trigeminal induced exteroceptive suppression of
trapezius muscle activity.
PMID- 9637940
TI - Masseter reflex potentials in olivo-ponto-cerebellar atrophy.
AB - We recorded masseter reflex potentials to examine the correlation between the
masseter reflex and the muscle stretch reflexes of limbs in 19 patients with
olivo-ponto-cerebellar atrophy (OPCA). The patients were subdivided into hyper-
(n = 5), normo- (n = 7) and hypo- (n = 7) reflexia groups according to the
degrees of the conventional deep tendon jerks in the upper limbs. The masseter
reflex potentials, elicited by tapping the chin with a reflex hammer, were
recorded from the bilateral masseters using a pair of surface electrodes. The
latency of the potentials in the hyporeflexia was significantly longer than in
the other groups, while the amplitude of those in the hyperreflexia group was
significantly higher than in the other groups. These results indicate that in
patients with OPCA the magnitude and latency of the masseter reflex correlates
with the status of the muscle stretch reflexes of the limbs in contrast with
Friedreich's ataxia where the masseter reflex has been reported to be normal or
hyperactive despite hyporeflexia in the limbs.
PMID- 9637941
TI - Suprascapular nerve conduction: a comparative analysis in normal subjects.
AB - An electromyographic examination is often utilized to confirm the diagnosis of
suprascapular neuropathy in patients with shoulder pain and dysfunction. The
purpose of this study was to compare three compound motor action potential (CMAP)
recording methods (surface electrode, monopolar needle, concentric needle) for
evaluating suprascapular nerve conduction. Twenty-two normal, healthy subjects
were tested with each method. Differences between the recording methods were
noted for CMAP latencies and amplitudes with the monopolar needle recordings
having the shortest mean latency and greatest mean amplitude. The monopolar
needle recordings also appeared to give a more reproducible measurement of CMAP
latency and evoked amplitude to the supraspinatus and infraspinatus. Therefore,
it may be more accurate to use a monopolar needle to record suprascapular nerve
conduction and determine abnormalities with a side-to-side latency difference of
0.4 ms being acceptable. Considering the diverse branching of the suprascapular
nerve, and the monopolar needle's relatively small sampling area of motor fibers,
it may be prudent to test conduction to multiple sites within these muscles for
the most accurate assessment.
PMID- 9637942
TI - Detection of nerve entrapment during limb lengthening by means of near-nerve
recording.
AB - Eight patients undergoing limb lengthening by the Ilizarov method had near-nerve
needle electrode conduction studies when they developed clinical signs of nerve
entrapment. The near-nerve technique was chosen because it is highly sensitive to
configurational changes which appear in the action potential as injury occurs. In
10 out of 13 symptomatic limbs the near-nerve potential was found to be
abnormally small and its usually smooth contour had become notched and irregular.
In the remaining 3 limbs the potentials were normal initially but became abnormal
as further constriction of the nerve took place. Nerve potentials remained normal
in size and shape in asymptomatic limbs undergoing lengthening and were not
altered by application of the Ilizarov frames themselves. The near-nerve
technique proved useful in the early detection of nerve injury in these patients
and thus enabled surgical intervention before nerve damage had become permanent.
PMID- 9637943
TI - Ratios of nerve conduction parameters in proximal to distal limbs remain constant
through the second to the eighth decades.
AB - We investigated the effect of age on nerve conduction parameters to establish a
diagnostic validity in demyelinating neuropathies of the aged. We evaluated 257
subjects (age 10-76 years old) with no history or signs of peripheral
neuropathies. The CMAP amplitude ratio (proximal CMAP/distal CMAP), duration
ratio, and area ratio were almost the same throughout the second to eighth
decades. The respective lower limits of the normal CMAP amplitude ratio (mean-3
SD) were 0.79 (median nerve), 0.75 (ulnar nerve), 0.57 (peroneal nerve), and 0.45
(tibial nerve). The upper limits of the normal CMAP duration ratio (mean +3 SD)
were 1.21 (median nerve), 1.22 (ulnar nerve), 1.37 (peroneal nerve), and 1.35
(tibial nerve). The lower limits of the normal CMAP area ratio (mean-3 SD) were
0.81 (median nerve), 0.78 (ulnar nerve), 0.60 (peroneal nerve), and 0.57 (tibial
nerve). No age-related changes were observed in the amplitude ratio or duration
ratio SNAP, although the standard deviation increased with age. Since the
amplitude, duration and area ratios are easily calculated and age-independent,
they can provide useful and reliable information on aged patients with
demyelinating neuropathies by conventional nerve conduction studies.
PMID- 9637944
TI - Neurophysiological studies in herpes simplex encephalitis.
AB - In herpes simplex encephalitis (HSE), simultaneous electro-encephalogram (EEG)
and evoked potential studies have not been reported, although EEG changes have
been described. In this communication, EEG, somatosensory and motor evoked
potentials have been reported in 9 patients with HSE. The patients' age ranged
between 2 and 70 years and 3 were females. Seven patients had seizures, CT scan
was abnormal in 6 and MRI in remaining 3 patients. Seven patients received
acyclovir therapy; one patient died and 6 had poor outcome. The initial EEG was
carried out within 5 days of ictus and was abnormal in all the patients. The EEG
abnormalities included frontotemporal delta slowing in 5, periodic lateralised
epileptiform discharge in 3, runs of spike and periodic activity in one patient
each. At 3 months, EEG was normal in 6 patients but it did not correlate with
clinical recovery. Central motor conduction time (CMCT) to upper limb and median
somatosensory evoked potential (SEP) were normal in all. CMCT to lower limbs and
tibial SEPs were unrecordable in one patient who had wide spread herpes simplex
virus (HSV-1) infection associated with AIDS, and died on 18th day of illness.
From this study, we conclude that EEG although is frequently abnormal and may
provide useful diagnostic information in a setting of encephalitis but evoked
potential changes are infrequent; and if present an association of HIV infection
should be considered.
PMID- 9637945
TI - Differential diagnosis of chronic idiopathic polymyositis and neuromyositis.
AB - The term neuromyositis indicates a very rare type of polymyositis where, beside
the usual muscular manifestations, there are signs of peripheral neuropathy.
Although a lot of patients with neuromyositis has been published, it is a very
controversial entity. There may be considerable difficulty in distinguishing
chronic polymyositis from neuromyositis, even with the aid of electromyographic
and muscle biopsy examinations. The aim of this investigation was to re-establish
the clues for distinguishing chronic polymyositis from neuromyositis. Fifty-seven
patients took part in this investigation. They were subdivided into two groups
according to EMG and muscle biopsy data. First group consisted of 29 patients
with chronic polymyositis and second group consisted of 28 patients with chronic
neuromyositis. Our data confirm the existence of neuromyositis as an entity with
different clinical, electromyographic and biopsy findings than polymyositis. The
differentiation between chronic polymyositis and neuromyositis is a difficult
task on purely clinical ground. Electromyographic recordings with widespread
myopathic features, some large potentials and spontaneous activity could be found
in both diseases. The most common and important electromyographic findings in
patients with neuromyositis are prolonged sensory and motor nerve conduction
velocities. In conclusion electromyography and muscle biopsy may be useful in the
differential diagnosis of polymyositis and neuromyositis.
PMID- 9637946
TI - The muscle inhibitory period by transcranial magnetic stimulation. Study in
stroke patients.
AB - Motor evoked potentials (MEPs) elicited over hand muscles by transcranial
magnetic stimulation (TMS) were studied in healthy individuals and, bilaterally,
in patients with cerebral infarction. Conduction time of the central motor
pathways (CMCT), threshold intensity, and amplitude of the MEPs were correlated
with recovery motor hand function after stroke. Following MEPs by TMS during
tonic muscle contraction, there is a transient suppression of muscle action. This
inhibitory period (IP) was significantly shorter in the upper paretic limb of
stroke patients with spasticity than in normal limb of the patients and healthy
individuals. Shortening of the IP duration was correlated to degree of upper limb
spasticity (Ashworth scale) and may be due to supraspinal level reduction of the
inhibitory function. The IP study contributes to a better quantification of the
hand function in stroke patients.
PMID- 9637947
TI - Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic
acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?
AB - A diet including 2-3 portions of fatty fish per week, which corresponds to the
intake of 1.25 g EPA (20:5n-3) + DHA (22:6n-3) per day, has been officially
recommended on the basis of epidemiological findings showing a beneficial role of
these n-3 long-chain PUFA in the prevention of cardiovascular and inflammatory
diseases. The parent fatty acid ALA (18:3n-3), found in vegetable oils such as
flaxseed or rapeseed oil, is used by the human organism partly as a source of
energy, partly as a precursor of the metabolites, but the degree of conversion
appears to be unreliable and restricted. More specifically, most studies in
humans have shown that whereas a certain, though restricted, conversion of high
doses of ALA to EPA occurs, conversion to DHA is severely restricted. The use of
ALA labelled with radioisotopes suggested that with a background diet high in
saturated fat conversion to long-chain metabolites is approximately 6% for EPA
and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to
50%. It is thus reasonable to observe an n-6/n-3 PUFA ratio not exceeding 4-6.
Restricted conversion to DHA may be critical since evidence has been increasing
that this long-chain metabolite has an autonomous function, e.g. in the brain,
retina and spermatozoa where it is the most prominent fatty acid. In neonates
deficiency is associated with visual impairment, abnormalities in the
electroretinogram and delayed cognitive development. In adults the potential role
of DHA in neurological function still needs to be investigated in depth.
Regarding cardiovascular risk factors DHA has been shown to reduce triglyceride
concentrations. These findings indicate that future attention will have to focus
on the adequate provision of DHA which can reliably be achieved only with the
supply of the preformed long-chain metabolite.
PMID- 9637948
TI - Radical oxidation of riboflavin.
AB - Riboflavin, lumiflavin and lumichrome were produced by light catalysis and gamma
irradiation. Their formation under various conditions was determined, and a
number of intermediates identified. Fluorescence excitation and emission spectra
were determined for the compounds and compared with the absorbency spectra. While
lumiflavin predominated in alkali and lumichrome in neutral solutions in the
light-catalyzed reaction, all products were produced to some extent under all
conditions. Gamma radiation resulted only in the formation of lumichrome, with no
observable intermediates.
PMID- 9637949
TI - delta-Aminolevulinate dehydratase inhibition by ascorbic acid is mediated by an
oxidation system existing in the hepatic supernatant.
AB - The effect of ascorbic acid (AA) on hepatic delta-aminolevulinic acid dehydratase
(ALA-D) activity was studied. AA decreased enzyme activity by reducing maximum
velocity and tended to increase the Michaelis constant. ALA-D inactivation by AA
occurred similarly both in air and argonium atmosphere incubation. DTT reduced
considerably the inhibitory effect of AA on ALA-D, but glutathione was
ineffective in reversing inactivation. These data indicate that inhibition occurs
mainly due to an acceleration of the oxidation rate mediated by the hepatic
supernatant utilizing AA in sulfhydryl groups of cysteine residues present at the
ALA-D active site. AA probably acts on cysteine from the ALA-D B site since
cucumber and radish leaves ALA-D was not inhibited by AA (up to 16 mM). The
addition of free radical scavengers to the medium did not alter ALA-D
inactivation caused by AA, indicating that active oxygen species formed during AA
oxidation were not directly related to -SH oxidation. The chelation of zinc ions
from the enzyme by EDTA turned ALA-D more susceptible to the inhibitory effect of
AA. This effect seems to involve mainly ZnB, which is known to bind to four
cysteines. The present data suggest that AA may participate in the regulation of
the heme biosynthesis pathway by promoting a reversible inactivation of ALA-D.
PMID- 9637950
TI - Usefulness of the prognostic inflammatory and nutritional index (PINI) in
hospitalized elderly patients.
AB - The prognostic inflammatory and nutritional index (PINI) is a simple scoring
system of overall health which aggregates two blood markers of inflammatory (C
reactive protein and alpha(1)-acid glycoprotein) and of nutritional (albumin and
transthyretin) states. This study was undertaken with a view to evaluate, in
comparison to currently used predictive approaches, the potential usefulness of
PINI to forecast hospital mortality and outcome of patients hospitalized in an
acute geriatric unit. 1,066 elderly patients, aged 82.7 +/- 6.6 years and
fulfilling inclusion criteria, were enrolled in the study. Logistic regression
analysis and calculation of relative risk (RR) were carried out for
epidemiological data with a cut-off value of 25 for PINI. Immediate mortality
(7.9%) of admissions) was predicted by PINI > or = 25 (RR = 4.34). Only 387
patients (36.3%) could rejoin their residence location (home or family). A
sizeable proportion of acute patients (55.8%) failed to recover and/or developed
diseased states requiring chronic care management. Incapacity to return home was
predicted by PINI > or = 25 (RR = 2.04). Hypoalbuminaemia < or = 30 g/L was not
found a predictor of mortality but was associated with total disability (RR =
9.08). The optimal PINI cut-off value to predict mortality was calculated at 8.8
using the ROC analytic approach. We conclude that the PINI formula is helpful to
predict both nearest lethality and chronic institutionalization. This scoring
system should take a place within the battery of tests used to identify and to
follow up acutely ill elderly patients at risk of major complications.
PMID- 9637951
TI - Nutritional status and serum lipids of a rural population in Northeast Thailand-
an example of health transition.
AB - An investigation was undertaken in Northeast Thailand, a country undergoing rapid
health transition, to find out whether there is a likelihood that the nutritional
and lipid pattern of an adult population in Northeast Thailand is related to
coronary heart disease in the same way as in western countries. In a cross
sectional study, the body mass index (BMI) and the waist-hip ratio as well as the
important plasma lipids were determined. The nutritional status and the lipid
profile of the predominantly middle-aged population is characterised by a
generally favourable nutritional status and lipid concentrations, where the
distribution, indicated by the medians, of the relevant variables over the total
population is concerned. A rather high proportion of individuals was found to be
overnourished and to have high triglyceride levels. Individuals with high
triglyceride levels run a risk of developing coronary heart disease only when the
LDL-HDL fraction is above 5. Only 3% of the total population investigated had a
LDL-HDL ratio above that value. Since hypertriglyceridaemia is also linked to the
insulin-resistant syndrome, it is concluded that, if the mortality of coronary
heart disease increases in future, then this must be accounted probably more to
the after-effects of the insulin-resistant syndrome than to the direct effect of
an atherogenic lipid pattern. This view is supported by a high prevalence of
impaired glucose tolerance (IGT) and non-insulin dependent diabetes mellitus
(NIDDM) in the population under survey. Preventive measures in the area should
concentrate among others on reducing overnutrition, especially among women, and
increasing physical activity and screening for NIDDM.
PMID- 9637952
TI - Nutritional and psychological status of young women after a short-term use of a
triphasic contraceptive steroid preparation.
AB - The present study was aimed to assess the psychological status of young healthy
women after the administration of a triphasic contraceptive steroid preparation
for six complete menstrual cycles. Subjects had never used oral contraceptives
(OC) and had neither a familial history of depression nor psychological
disturbances. OC-induced psychological disturbances were interpreted for years as
evidence of pyridoxine (vitamin B6) deficiency. Other nutritional deficiencies,
namely in cobalamin, folate and iron, can disturb the functioning of the central
nervous system. In addition, a deficiency of any of these nutrients can lead to
several anemia-induced symptoms that are highly susceptible to influence the
psychological status. For ample evidence, nutritional status was then evaluated
in parallel to psychological testing. Blood iron and vitamin levels of interest
were found to be adequate and could not have biased the response to a
psychological test (MMPI). This study showed that a 6-month Triphasil treatment
did not modify significantly the psychological status of subjects. To our
knowledge, this is the first psychological study on young never OC-users taking
an identical triphasic contraceptive steroid preparation to investigate early
psychological side-effects due to OC, at a similar time of the menstrual cycle,
when nutritional status was also evaluated.
PMID- 9637953
TI - Effects of feeding fresh garlic and garlic oil on detoxifying enzymes and
micronuclei formation in rats treated with azoxymethane.
AB - The effect of feeding a fresh garlic or garlic oil-supplemented diet was studied
in rats for a period of 23 weeks with or without the treatment of a carcinogen
azoxymethane (AOM), on the modulation of detoxification enzymes and micronuclei
formation. The results showed that feeding fresh garlic or garlic oil
supplemented diets tended to reduce hepatic lipid peroxidation, though not to
significant levels. Glutathione content was also not altered. The catalase
activity in liver of rats fed a fresh garlic-supplemented diet was reduced
compared to that of the control diet; however, the activity was not affected by
AOM treatment. Ingestion of garlic caused a 40 percent increase in the hepatic
glutathione peroxidase activity, whereas carcinogen treatment reduced it. The
activity of hepatic glutathione-S-transferase was unaffected by the feeding
regimen, while it was lowered in the garlic oil diet group treated with AOM. The
gamma glutamyl transpeptidase activity was elevated more than sevenfold, in the
kidney of rats treated with AOM, while it was reduced almost to half when the AOM
treated rats were fed fresh garlic or garlic oil. Micronuclei formation was
increased fourfold, in rats exposed to AOM whereas the increase was reduced to
half when AOM-injected groups had either fresh garlic or garlic oil in their
diet. From these studies, it is concluded that long-term feeding of garlic, fresh
or oil, reduced the toxic effect of AOM in rats.
PMID- 9637954
TI - Cardiovascular disease myths and facts.
AB - Myths about cardiovascular disease--that the problem is going away, that it is a
"good" way to die, and that no further research is needed--are undermining
prevention efforts and funding for research. Physicians need to counteract these
myths.
PMID- 9637955
TI - Kuru and mad cow disease: understanding the prion theory.
AB - A preponderance of evidence indicates that several neurodegenerative disorders
are caused by prions: abnormally folded proteins that can induce abnormal folding
in other normal protein molecules. Further, these "infections" can cross some
species barriers.
PMID- 9637956
TI - The hospitalist: will inpatient specialists improve care?
AB - The number of hospitalists--i.e., practitioners who specialize in the care of
hospital inpatients--is growing rapidly in the United States. In part a response
to managed care's push for better health outcomes with a minimum waste of time,
effort, and money, this new specialty has its own national organization,
affiliated with the American College of Physicians. Challenges to hospitalists
include minimizing the use of consultations and unnecessary laboratory tests for
inpatient care, and ensuring continuity of care once patients leave the hospital.
PMID- 9637957
TI - Sildenafil (Viagra) for treating male erectile dysfunction.
AB - Sildenafil, the first oral drug for treating male erectile dysfunction, appears
effective and well tolerated. However, more time and experience will be needed to
establish this drug's true efficacy and safety.
PMID- 9637958
TI - Infectious disease and transplantation: messages for the generalist.
AB - Today, more patients than ever are receiving organ or bone marrow transplants and
are surviving longer afterward. Because these patients often live far from the
transplant center, their local primary care physicians may be called on to
evaluate problems as they arise, although all significant issues should be
handled in conjunction with the transplant team. This paper reviews the primary
care physician's role in the pretransplantation evaluation, and in coordination
of long-term care, as well as illustrative cases.
PMID- 9637959
TI - Managing solitary pulmonary nodules.
AB - A solitary pulmonary nodule (SPN) on a chest radiograph represents a major
diagnostic dilemma. The goals of management are to resect malignant tumors
without delay and to avoid unnecessary thoracotomy if the nodule is benign. But
because of the difficulty distinguishing benign from malignant nodules, even with
advances in imaging techniques, these goals cannot be met in all cases.
PMID- 9637960
TI - A 61-year-old woman with edema, shortness of breath, and pleuritic chest pain.
PMID- 9637961
TI - Some perspective on Viagramania.
PMID- 9637962
TI - The promises and risks of inpatient specialization.
PMID- 9637963
TI - Devolution of power: an interim report card.
AB - During the mid-1990s liberals hoped that states would enact health insurance
expansions, while conservatives looked to the states to contain costs. This essay
considers whether states are meeting these great expectations. I review state
performance in four policy priorities: encouraging Medicaid clients to enroll in
managed care; expanding insurance coverage for children; making insurance more
available and more affordable for the small-business community; and containing
long-term care costs. The review suggests that states cannot accomplish these
tasks without federal help. Congress seems to be getting the message and has
enacted its own child health and insurance reform legislation. This trend is
overdue and welcome.
PMID- 9637964
TI - Assessing the new federalism: an introduction.
PMID- 9637965
TI - A different kind of 'new federalism'? The Health Insurance Portability and
Accountability Act of 1996.
AB - The Health Insurance Portability and Accountability Act (HIPAA) of 1996 has been
praised and criticized for asserting federal authority to regulate health
insurance. We review the history of federalism and insurance regulation and find
that HIPAA is less of a departure from traditional federal authority than it is
an application of existing tools to meet evolving health policy goals. This
interpretation could clarify future health policy debates about appropriate
federal and state responsibilities. We also report on the insurance environments
and the HIPAA implementation choices of thirteen states. We conclude with
criteria for judging the success of HIPAA and the evolving federal/state
partnership in health insurance regulation.
PMID- 9637966
TI - Medicaid managed care in thirteen states.
AB - This study examines the recent expansion of Medicaid managed care from the
perspective of the thirteen states in the Urban Institute's Assessing the New
Federalism project. States are moving to managed care for Medicaid both to
improve beneficiaries' access and to control the growth in program costs.
However, we find that despite dramatic growth in enrollment during this decade,
few states are enrolling the elderly or the disabled--the most expensive Medicaid
beneficiaries. We also conclude that cost-savings objectives are often at odds
with goals of contracting with mainstream plans and protecting safety-net
providers.
PMID- 9637967
TI - Transformations in public health systems.
AB - Public health systems are undergoing major changes. Historically, population
oriented services framed the responsibilities of the public health system. Yet
over time, clinical services, particularly maternal and child health care, became
an important component. More recently, many public health agencies have begun to
refocus on traditional services, largely in response to Medicaid managed care and
an associated decline in clients. This paper examines such transformations in
thirteen states.
PMID- 9637968
TI - State policy on long-term care for the elderly.
AB - In the thirteen Assessing the New Federalism states, strategies to control the
rate of increase in long-term care spending are extremely varied, especially in
comparison with acute care's single-minded focus on managed care. States use
three broad strategies: offsetting state spending with increased private and
federal contributions, making the delivery system more efficient, and using
traditional cost-control mechanisms, including controlling the nursing home bed
supply and cutting Medicaid reimbursement rates.
PMID- 9637969
TI - Publicly subsidized health insurance: a typology of state approaches.
AB - Using information from case studies, published documents, and the Current
Population Survey, this paper describes and classifies state approaches to
providing health insurance to low-income populations (as of 1997). It examines
the link between the scope of state efforts and uninsurance rates for low-income
populations. Findings indicate that the breadth of state policies contributes to
differences in insurance coverage for low-income persons across states.
PMID- 9637970
TI - Changing state and federal payment policies for Medicaid disproportionate-share
hospitals.
AB - The Medicaid disproportionate-share hospital (DSH) program has been the subject
of considerable policy debate throughout the 1990s, prompting Congress to revise
the program three times since 1991. Using Medicaid administrative data and
information obtained from twelve state case studies, we examined how the study
states dealt with the federal reforms. We found a variety of state responses,
ranging from not spending their full DSH allotments to seeking new, "DSH-like"
federal money to help support safety-net providers.
PMID- 9637971
TI - Welfare and immigration reforms: unintended side effects for Medicaid.
AB - Welfare reform and changes in immigrants' eligibility may lead to significant
reductions in Medicaid caseloads, even though many states are expanding Medicaid
eligibility rules to accommodate changes under the new welfare programs. In 1996,
for the first time in almost a decade, Medicaid participation of adults and
children fell about 2 percent, and further reductions seem likely in 1997. The
gradual restrictions on new immigrants also will affect future caseloads.
Although new initiatives such as the State Children's Health Insurance Program
(CHIP) should expand health coverage for children, the welfare reform and
immigration changes will disproportionately lead to loss of insurance among
adults.
PMID- 9637972
TI - A broader vision for managed care, Part 1: Measuring the benefit to communities.
AB - For the past quarter-century managed care plans have been judged almost
exclusively in terms of their influence on the health and health care of
individual enrollees. However, policymakers are now paying attention to the ways
in which health care organizations affect the broader well-being of their
communities. These forms of "community benefit" emerged originally from legal
criteria for tax exemption but are increasingly applied to all health care
organizations, whatever their form of ownership. In this paper we identify
different paradigms for defining community benefit and trace the factors that
have encouraged or discouraged their application to health care. We suggest
several strategies encouraging managed care plans to broaden their goals to
include community benefit.
PMID- 9637973
TI - Access to care: how much difference does Medicaid make?
AB - Using the 1994 Robert Wood Johnson Foundation National Access to Care Survey, we
examine the likelihood of having a usual source of care, inability to obtain
needed care, and number of physician visits for persons with private insurance,
Medicaid coverage, and no insurance. Inability to obtain services is surprisingly
consistent: For each service, Medicaid enrollees were about half as likely as
uninsured persons and about twice as likely as privately insured persons were to
report difficulty. For other access measures, access for those on Medicaid more
closely resembles that of the privately insured than that of the uninsured.
PMID- 9637974
TI - Balanced federalism and health system reform.
PMID- 9637975
TI - Medicaid's problem children: eligible but not enrolled.
PMID- 9637976
TI - Mental health insurance in the 1990s: are employers offering less to more?
PMID- 9637977
TI - Consolidation of the inpatient medical rehabilitation industry.
PMID- 9637978
TI - Managed competition in practice: 'value purchasing' by fourteen employers.
AB - Many large U.S. companies have transformed their procurement of health benefits
in the 1990s by combining the principles of managed competition with other
business tactics to create a business-savvy hybrid of the private sector's own
design, often referred to as "value purchasing." Until recently, few policymakers
or health care observers believed that large firms would be a force in health
system reform. Yet to implement value purchasing, the large companies in this
study created new organizational forms, provided employees with financial
incentives to select low-cost health plans, and used business tactics such as
competitive bidding to negotiate more favorable rates and to improve quality
among health plans. The financial results were impressive for the companies
studied. In addition, the companies' demands on the health care delivery system
are multiplying as the interface between business firms and health care
organizations changes. These demands will only increase as the practices we found
become more widespread.
PMID- 9637979
TI - Independent practice association physician groups in California.
AB - We surveyed independent practice association (IPA) physician groups in California
about their approaches to staffing, physician payment, and governance. Most IPAs
desired more primary care physicians but not more specialists. Capitation was the
major mode of remuneration for primary care physicians in 77 percent of IPAs, and
for specialists in 30 percent of IPAs. Most IPAs also used financial incentives
related to use of referral or ancillary services. Boards of directors were
dominated by physicians, but governance tended to be centralized rather than
highly democratic. We found that IPAs mirror many of the broader trends in
physician staffing and physician payment that exist in managed care
organizations.
PMID- 9637980
TI - Managed care and low-income populations: recent state experiences.
AB - This DataWatch examines the relationship between managed care enrollment and
access to care for low-income adults with Medicaid and compares their experience
with that of low-income, privately insured managed care enrollees. Medicaid
managed care enrollees are more likely than low-income, privately insured managed
care enrollees to be poorer, have health problems, and experience access
problems. Compared with low-income populations in fee-for-service care, managed
care enrollees, whether in Medicaid or privately insured, are not appreciably
different in having a usual source of care, having a regular provider, or
emergency room use but report more problems in obtaining care and are more likely
to be dissatisfied with their health plans.
PMID- 9637981
TI - Creating partnerships with clinic associations to preserve the safety net.
PMID- 9637982
TI - How will states implement children's health insurance programs?
PMID- 9637983
TI - Dealing with Dolly: inside the National Bioethics Advisory Commission.
PMID- 9637984
TI - Health care and consumers: some amplification.
PMID- 9637985
TI - Can physicians manage physicians?
PMID- 9637986
TI - Medicare reform.
PMID- 9637988
TI - Emergency departments are not the problem.
PMID- 9637987
TI - Health insurance for low-income adults: the issue of Hispanics.
PMID- 9637989
TI - The 'shoe-box effect'.
PMID- 9637990
TI - Doctors as decisionmakers.
PMID- 9637991
TI - Research needs for rural and environmental health in central Europe.
PMID- 9637992
TI - Occupational health in Germany and other countries of the European Union.
AB - Occupational medicine is affected to a much greater extent by national legal and
social conditions than by clinical issues. The different preconditions specific
to each country serve to restrict the scientific dialogue on issues of
occupational medicine. Therefore, in this paper are described the organisation
and the under- and postgraduate education of occupational medicine in Germany and
other European countries (Austria, Belgium, Denmark, Italy, United Kingdom). In
summary one can state that in many member states of the EU there is a lack of
undergraduate training in occupational medicine for students and there are
distinct systems for the postgraduate training and assessment of occupational
physicians. The practice of occupational medicine in the EU countries probably
has many similarities. The responsibilities of occupational physicians are rather
comparable, though in some countries the approaches of occupational medical
prevention and the interest in evaluating the structure, process and outcome of
many of the activities of occupational medicine seem to recede something into the
background.
PMID- 9637993
TI - Separate and combined effects of the outdoor and indoor air quality on chronic
respiratory symptoms adjusted for allergy among preadolescent children.
AB - The purpose of the study was (a) to assess whether the respiratory effects of
outdoor air pollutants may be replicated after correcting for indoor air quality
(environmental tobacco smoke, home heating and damp or mold houses), (b) to
evaluate whether the extent of the allergic status of children modifies the
respiratory health due to air pollution, and (c) to determine whether the higher
prevalence of respiratory symptoms in more polluted areas of the city may be
explained by excess in allergy. The survey targeted 1,129 school children, nine
years of age, attending schools in Cracow, located in the areas with different
levels of the outdoor air pollution. Based on the measurements obtained from the
air pollution monitoring stations and the information provided by parents on the
sources of local emission of air pollutants, four categories of air pollution
areas have been defined. Chronic phlegm as a single symptom was unrelated to
allergy but associated with the outdoor air pollution score. The prevalence odds
ratio (OR) for this symptom between the contrasting areas of outdoor air
pollution, i.e. very high pollution versus very low, was 5.85 (95% CI: 1.05
32.6). Except for chronic phlegm, the outdoor air pollution score was associated
only with hay fever when adjusted for indoor characteristics and allergy. After
adjustment for air pollution and allergy, the presence of molds or dampness in
the house was significantly related to hay fever (OR = 2.1, 95% CI: 1.5-3.0),
wheezing (OR = 1.6, 95% CI: 1.1-2.5), and difficulty in breathing (OR = 2.0, 95%
CI: 1.2-3.3). In terms of attributable fraction (AF(pop)), the effect of outdoor
air pollution on the occurrence of allergy in children was significant (AF(pop) =
22.3%). The impact of allergy on the occurrence of respiratory symptoms (two or
more respiratory symptoms) was stronger (AF(pop) = 52.1%) than that of the
outdoor air pollution level (AF(pop) = 21.6%) or that of molds/dampness at home
(AF(pop) = 14.1%).
PMID- 9637994
TI - Occupational profile and cardiac risk: possible mechanisms and implications for
professional drivers.
AB - There has been at least forty empirical investigations concerning cardiovascular
disease (CVD) among professional drivers (PDs). Standard cardiac risk factor
status does not consistently distinguish PDs from other lower risk groups. PDs
showed more than twice the overall exposure to stressful work factors compared to
referents. They also showed lower maximum bicycle exercise level with a higher
double product and higher diastolic blood pressure at the end of exercise
compared to controls. Catecholamine excretion has been reported to be elevated
during driving. Ambulatory measurements showed higher systolic and diastolic
blood pressure in drivers before, during and after driving shifts. Using spectral
analysis, the low to high frequency ratio was more than doubled towards the end
of a 4-hour drive compared to the early one and a linear increase in 0.1 heart
rate variability as a function of distance driven. Reactivity to headlight glare
has been shown to roughly parallel the degree of CVD severity in PDs with IHD,
essential and borderline hypertension. It was postulated that PDs with IHD form a
powerful association between the exposure to glare and the stressfulness of
driving and this association was resistant to extinction. The occupational
medicine specialist "should have the authority to check the patient regularly in
the workplace itself (to ascertain whether or not) the decision to return to work
is still valid". An integrated diagnostic approach for PDs might entail using
exercise stress testing, with evaluation of silent myocardial ischaemia and heart
rate variability during work as well as laboratory tests which simulate aspects
of their work environment, with catecholamines measured in relation to these
procedures. Assessment of left ventricular mass and further evaluation of
atherogenic biochemical abnormalities would be of value for further untangling
the mechanisms of cardiac risk among PDs.
PMID- 9637995
TI - Blood lead levels in industrial workers in Poland.
AB - Occupational exposure to lead occurs in about 1,300 enterprises in Poland.
According to the 1994 data, based on the reports of the State Sanitary
Inspectorate, 1,970 persons were employed at that time under conditions of
exposure exceeding the Polish MAC level of 0.050 mg/m3. The measurements of
workers' blood lead concentrations (Pb-B) were carried out only in 90 factories.
In 1996, the Minister of Health and Social Welfare issued a directive stating
that the Pb-B determinations in employees occupationally exposed to lead are
compulsory. The aim of the present study was to assess lead exposure of workers
employed in different branches of the Polish economy, based on Pb-B
determinations. The measurements were performed on 2,324 male and 165 female
workers of 13 different types of industry, including manufacture of crystal
glass, battery industry, copper and zinc smelters, welding in a repair shipyard
and some other workposts under conditions of lead exposure. The results of the
determinations indicate that exposure to lead continues to be a serious problem
in Polish industry. Pb-B concentrations exceeded the newly introduced Polish
biological exposure index (BEI) value of 500 micrograms/l for men workers in
about 30% of workers examined in 1996. In about 65% of females under 45 years of
age the Pb-B concentrations were higher than 300 micrograms/l recommended as BEI
for this age group. Considering the WHO-recommended health-based maximum
individual biological action level of 400 micrograms/l, the percentage of the
employees for whom higher values were found amounted to about 45% for men
workers. The results point to the necessity of enforcing the implementation of Pb
B determinations according to the ministerial ordinance as well as of removing
from exposure the workers with Pb-B levels exceeding the present BEI values. The
improvement of working conditions and the implementation of health education for
workers are also the actions to be promptly undertaken. In order to achieve these
goals a close cooperation is required between the State Sanitary Inspectorate,
the institutes of occupational health as well as the employers and trade unions.
PMID- 9637996
TI - Occupational hearing loss among selected farm tractor operators employed on large
multiproduction farms in Poland.
AB - A specially selected group of 45 farm tractor drivers were examined in order to
estimate the degree of occupational hearing loss. The drivers, aged 21-50 years,
were employed on multiproduction farms. The study showed that the operators under
study had statistically worse hearing within the range of high frequencies (3-6
kHz), especially those aged over 30 years, compared to the control group of the
same age. An intolerable hearing loss (over 20 dB) was noted among 56% of
operators within the highest frequency range (3, 4 and 6 kHz), and among 22% of
operators in the range of medium frequencies (0.5, 1, 2 and 3 kHz), with no
hearing loss observed in the control group. Based on analysis of data concerning
all operators it was noted that age and the period of employment in agriculture
were highly correlated with hearing loss (r = 0.45-0.57). A series of
correlations and linear regression analyses, conducted in two age intervals,
showed that in the group of young operators (under 35 years) a statistically
significant, strong correlation was observed between hearing loss and the period
of employment (right ear: r = 0.60-0.65), whereas in the older age group (over 35
years) hearing loss was more strongly correlated with age than with the period of
employment, although this correlation was not statistically significant. The
results obtained confirmed that the detected hearing loss among operators of farm
tractors was caused by exposure to occupational noise present on farms.
PMID- 9637997
TI - Development of occupational exposure limits in Japan.
AB - The development of occupational exposure limits (OELs) in Japan is discussed by
describing the OELs of two chemical compounds, benzene and trichloroethylene, as
typical examples. As for benzene, sufficient epidemiological evidence has
accumulated indicating that benzene is a human carcinogen. To establish the OEL
for benzene, the OEL committee of the Japan Society for Occupational Health
(JSOH) selected 9 cases of acute myeloic or monocytic leukemia out of the 14
cases of leukemia in the Pliofilm cohort, adopted the exposure estimate of
Paustenbach et al. (52), and calculated the risk of benzene-induced leukemia by
means of an average relative risk model. The lifetime risk of leukemia by
exposure to benzene at 1 ppm for 40 years was calculated as 0.762 x 10(-3) with a
95% confidence interval between 0.621 x 10(-3) and 0.98.10(-3). The benzene level
that causes one lifetime excess death from leukemia among 1,000 workers exposed
to benzene for 40 years was 1.31 ppm, with a 95% confidence interval between 1.01
and 1.61 ppm. The OEL committee decided that benzene exposure should be
controlled by a reference value corresponding to a lifetime risk (10(-3) or 10(
4)) of leukemia rather than by a time-weighted average (TWA) concentration. The
committee has proposed that the benzene exposure level corresponding to the
lifetime risk of 10(-3) is 1 ppm and that corresponding to the risk of 10(-4) is
0.1 ppm. In 1995, the International Agency for Research on Cancer (IARC) changed
the carcinogenicity classification of trichloroethylene from Group 3 (not
classifiable as to carcinogenicity to humans) to Group 2A (probably carcinogenic
to humans). The OEL committee of the JSOH, however, reached the conclusion that
since it has not been confirmed that trichloroethylene is a human carcinogen, and
since carcinogenicity, if any, may be based on an epigenetic rather than
genotoxic mechanism, it is not appropriate to establish the OEL of
trichloroethylene presupposing that trichloroethylene is a carcinogen. The
judgment of the OEL committee is that the OEL for trichloroethylene should be
established on other than carcinogenicity findings, particularly on the basis of
its neurological effects. In the light of accumulated evidence that a long-term
exposure to trichloroethylene at 50 ppm will cause neurotoxic effects to
industrial workers, the OEL committee has proposed 25 ppm (135 mg/m3) as a
reference value for work environments. Finally, we propose that the general
environmental air standards of benzene and trichloroethylene should be about
1/1,000 of the respective reference values for work environment.
PMID- 9637998
TI - Excess mortality in working age males in Poland: general patterns.
AB - Since the second World War, excess mortality of males has been steadily growing
in Poland. The aim of this paper was to analyze the basic relationships between
excess male mortality and some social and economic factors, with special
reference to both age and place of residence. Data published in Demographic
Yearbooks and included in reports produced by the Government Population Council
were used in the analysis. The excess male mortality is expressed in terms of
male/female mortality ratio, and also in terms of the difference between the
average female and male life expectancy. In the early 1990s the general male
mortality rate in Poland was by 23% higher than the general female mortality
rate, whereas in males at younger working age (20-44 years) mortality was three
times higher, and in the older age (45-64 years) groups 2.7 times higher than the
female mortality. Compared with the majority of European countries, Poland is
characterised by high rates of excess male mortality, which points to a
deteriorated health status of the population. At present, excess mortality of the
working age males is much higher than in the 1960s and 1970s. Our analysis of the
1960-1994 trends revealed that the highest excess male mortality occurs in the 20
24 age group. Although recently a falling trend has been observed in the infant,
juvenile and post working age groups, a continuous increase is noted in the
working age population of Poland. Causes of death were also included in our
analysis. Among circulatory diseases, the highest excess mortality was due to
acute myocardial infarction (the risk of death from this disease was 8 times
higher for males than for females). Accidents, injuries and poisoning constitute
another leading group of causes responsible for excess mortality (6/1 male/female
death risk ratio). The excess male mortality rates are higher in the rural than
in the urban areas. The excess male mortality was also reflected in the indices
of average life expectancy. In 1995, the average life expectancy was 67.6 years
for males and 76.4 years for females. Thus, in Poland males live 8.6 years
shorter than females on average. Increased excess mortality among the working age
males, a considerable difference between male and female average life expectancy,
disturbed demographic male/female balance, these are at least some of the reasons
why further in depth studies of excess male mortality in Poland should continue.
PMID- 9637999
TI - Polish bibliography of occupational medicine, 1996. Part 3.
PMID- 9638000
TI - Timely learning by consensus.
PMID- 9638001
TI - A quantitative comparison of machined commercially pure titanium and titanium
aluminum-vanadium implants in rabbit bone.
AB - Screw-shaped implants made from rods of commercially pure titanium (grade 1) and
titanium-aluminum-vanadium (grade 5) were machined, and the implant surface
structures were numerically described before being placed in rabbit tibiae for
healing periods of 1 months, 6 months, and 12 months. Quantitative comparisons of
the removal torque (Ncm) necessary to loosen the implants from the bone bed were
performed. Short-term (1 month) observations revealed no significant differences
between the two tested materials. However, after 6 and 12 months, the
commercially pure titanium implants were significantly more stable in the bone
bed, as compared to the alloy samples. After 6 months, the commercially pure
titanium had a mean removal torque of 29 Ncm versus 23 for the alloy (P = .01),
and after 12 months, the mean removal torque was 38 Ncm for commercially pure
titanium as compared to 35 Ncm for the alloy (P = .01). Quantifications of the
bone tissue response to the materials did not show any significant differences;
however, the commercially pure titanium showed a tendency to have a higher
percentage of bone in contact with the implant as compared to the alloy screws.
Bone volumes in the threads were similar. The absence of any quantitative light
microscopic difference after 1 month following placement may relate to the fact
that there was a sparse amount of bone, since the tissue was in the
organization/granulation phase. After 6 and 12 months of follow-up, substantial
bone formation had occurred, resulting in significantly increased removal torques
for the commercially pure titanium samples.
PMID- 9638002
TI - The treatment dilemma of the furcated molar: root resection versus single-tooth
implant restoration. A literature review.
AB - Successful treatment of furcated molar teeth presents the periodontist and
prosthodontist with a challenging dilemma. Accepted treatment modalities include
chemotherapeutic maintenance, root planning, open flap debridement, modified
Widman flap, bone grafting with and without guided tissue regeneration, and
osseous resection with and without root removal. Determining the appropriate
treatment for an individual patient that is both cost-effective and offers the
greatest long-term prognosis can be a daunting task. The literature is replete
with studies of different therapeutic alternatives for furcated molar teeth. A
relatively new treatment option is complete removal of the tooth combined with
ultimate placement of an endosseous implant and restoration with a single crown.
A review of the relevant literature with special emphasis on root resection
therapy and single molar implant placement is presented. The relative merits of
each treatment modality and guidelines for their use are discussed.
PMID- 9638003
TI - Implants placed in immediate extraction sites: a report of histologic and
histometric analyses of human biopsies.
AB - Five titanium plasma-sprayed implants were biopsied from a human volunteer 6
months after placement. Four test implants had been placed in immediate
extraction sockets, while one implant was placed in a mature site and served as a
control. The histologic analysis demonstrated that all five implants achieved
osseointegration as demonstrated by light microscopy, whereas a varying degree of
bone-implant contact was observed. The non-loaded control implant had the highest
percentage of bone-implant contact, 72%, followed by the two implants placed in
the canine sites presenting with a horizontal defect dimension of 1.5 nm or less.
These implants were placed without a barrier membrane, but in a submerged
fashion. The histometric analysis showed a mean bone-implant contact of 50% for
these two implants. The lowest mean bone-implant contact (17%) was observed for
the two molar implants, which had horizontal defect dimensions of 4 mm; these
implants were placed in a non-submerged fashion with the implants perforating an
expanded polytetrafluoroethylene membrane. The authors concluded that
osseointegration may occur in immediate extraction sites in humans using titanium
implants with a plasma-sprayed surface. The horizontal component of the peri
implant defect was apparently the most critical factor relating to the final
amount of bone-implant contact.
PMID- 9638004
TI - Bone response to functioning implants in dog mandibular alveolar ridges augmented
with distraction osteogenesis.
AB - The specific aim of this study was to determine the response of alveolar bone
after it was augmented vertically using distraction osteogenesis and subsequently
loaded with implant restorations. Four dogs each had four implants placed
horizontally into an edentulous mandibular quadrant and, after integration, a
distraction osteogenesis device was fabricated in the laboratory. An osteotomy
was made to allow the crest of the alveolar ridge to be distracted vertically.
After 10 mm of vertical distraction, the device was stabilized with light cured
resin. Following bone fill confirmation of the distraction gap at 10 weeks, two
implants were placed into the ridges, one in distracted bone and one in
nondistracted bone. After 4 months for implant integration, freestanding
prostheses were fabricated. Crestal bone levels were evaluated throughout the
period of function. Animals were sacrificed after 1 year of loading, for
histologic evaluation of the bone. The vertical ridge augmentation averaged 8.85
+/- 1.05 mm after 10 weeks of healing following distraction, without change over
1 year of implant loading. Histologic examination showed that bone had formed
between the distracted segments, creating an augmented ridge. The average
thickness of the labial cortex in the distraction gap was significantly thinner
than the lingual cortex in distracted bone and the lingual and labial
nondistracted cortical bone. The presence of the dental implant did not
significantly affect cortical bone thickness. Serial sections showed that
implants remained integrated and functional without soft tissue inflammation.
Dental implants placed into alveolar ridges augmented with the technique of
distraction osteogenesis maintained bone and were functional for the length of
this study.
PMID- 9638005
TI - Telescopic prostheses for implants.
AB - This retrospective study investigated the outcome of 73 telescopic implant
supported fixed prostheses. Fifty-four prostheses were entirely cement-retained,
and 19 incorporated a screw-clamping unit. The rate of complications was low and
in most cases minor in nature. Cement-retained prostheses involving a distal
cantilevered extension required the greatest postoperative maintenance. Despite
the small number of combined screw- and cement-retained prostheses, the lack of
complications and ease of retrievability make this approach worthy of further
study.
PMID- 9638006
TI - Report of 302 consecutive ridge augmentation procedures: technical considerations
and clinical results.
AB - Three hundred two consecutive ridge augmentation procedures (289 in a
buccolingual and 13 in an apico-occlusal direction) were performed in 284
patients. Gore-Tex membranes of various configurations were used in conjunction
with various nonautogenous particulate materials. Two hundred ninety-one of the
augmented ridges (279 buccolingual and 12 apico-occlusal augmentations)
demonstrated sufficient regenerated hard tissues for implant placement in ideal
prosthetic positions. This represents an overall "success" rate of 96%, 97% for
horizontally augmented ridges and 92% for vertically augmented ridges. A total of
574 implants were placed in the augmented ridges; 346 of these implants have
subsequently been uncovered and restored. Seven implants failed to achieve
osseointegration, and three implants (in one patient) were lost in function, for
an overall survival rate of 97% for the uncovered implants.
PMID- 9638007
TI - Mandibular implant-retained overdenture: finite element analysis of two anchorage
systems.
AB - Transmission of masticatory load in mandibular implant-retained overdentures was
evaluated using a three-dimensional finite element model. The reaction forces on
the distal edentulous mucosa and the stress on the perimplant bone were compared
in overdentures retained either by two ball attachments or by two clips on a bar
connecting two implants. In the finite element model, a 35 N load on the first
mandibular molar induced a greater reaction force on the distal edentulous ridge
mucosa of the nonworking side when the overdenture was anchored by ball
attachments than with the clips/bar attachment. Stress on peri-implant bone was
greater with the clips/bar attachment than with the ball attachment.
PMID- 9638008
TI - Mobility assessment with the Periotest system in relation to histologic findings
of oral implants.
AB - The relationship between mobility assessment with the Periotest system and
histologic findings was evaluated for oral implants. Five screw-type implants of
pure titanium were placed in the mandibles of four monkeys. Two implants in each
monkey were occlusally overloaded. These implants were brushed once a week.
Plaque was allowed to accumulate around unloaded implants with abutments in the
same monkeys. During the experiment, six of eight implants with occlusal overload
showed increased manually detectable mobility. Two of these were lost. After 18
months of experimentation, the mobility was assessed using the Periotest system.
Sections of the implants and surrounding tissue were cut. For the excessive
occlusally loaded implants with manually detectable mobility, positive Periotest
values were recorded, and for all other implants the values were negative (range
= -7 to -2). All implants with plaque accumulation were histologically
osseointegrated but showed marginal bone loss. Two of the implants with occlusal
overload had lost osseointegration completely, and two other implants were
osseointegrated in the apical part only. A statistically significant association
between the Periotest values and the histologic bone level or the proportion of
bone-implant contact was observed. If only clinically stable implants (i.e.,
without manually detectable mobility or with a negative Periotest value) were
included in the analysis, no significant correlation was found. The Periotest
values revealed only slightly more information concerning the osseointegration of
implants than manual mobility assessments.
PMID- 9638009
TI - Mandibular onlay grafting using prefabricated bone grafts with primary implant
placement: an experimental study in minipigs.
AB - The aim of this experimental study was to evaluate the use of prefabricated
autogenous bone grafts as onlay grafts to the mandible. Excess bone of 10 x 12 x
40 mm was produced inside blocks of pyrolyzed bovine bone under a polylactic
membrane coverage on the outside of the mandible in 15 adult Gottingen minipigs.
After 5 months, this bone was harvested and transferred to the premolar region of
the mandibular body in 10 animals. Onlay grafts of mandibular bone were used as
controls for the transplanted prefabricated grafts. All grafts were fixed by
primary placement of one titanium implant each. Five animals served as ungrafted
controls. Evaluation was performed after 3 months and 5 months, respectively. Two
animals were lost to evaluation, and one scaffold became infected. Eleven of the
remaining 12 scaffolds showed sufficient bone ingrowth for grafting. Three months
after transplantation, bone volume of the prefabricated grafts was almost
completely preserved, with only minimal resorption in the superficial pores of
the scaffolds, while the control grafts exhibited partial resorption. The
titanium implants, which had been placed at the time of only grafting, exhibited
direct bone-implant contact. Five months after grafting, all titanium implants
showed complete osseointegration, with direct bone-implant contact. The grafted
bone exhibited a significant increase in bone density by appositional bone
formation. The control grafts were nearly completely resorbed at that time.
PMID- 9638010
TI - Tridimensional reconstruction of knife-edge edentulous maxillae by sinus
elevation, onlay grafts, and sagittal osteotomy of the anterior maxilla:
preliminary surgical and prosthetic results.
AB - The possibility of placing endosseous implants in the edentulous maxilla is
frequently reduced by inadequate bone volume of the residual ridge. In totally
edentulous maxillae with knife-edge conformation, insufficient thickness is
frequently associated with insufficient height of the residual ridge in the
posterior maxilla because of pneumatization of the maxillary sinuses. This
surgical method combines grafting of the maxillary sinuses, onlay grafts on the
buccal side of maxillary posterior segments, and sagittal osteotomy of the
anterior maxilla with interpositional bone grafts. Five to six months after
maxillary reconstruction, Branemark implants were placed and, after
osseointegration occurred, implant-supported dental prostheses were fabricated.
Three patients have been treated with this method and 22 implants have been
placed. The mean follow-up after final prosthetic rehabilitation has been 16
months; survival rate has been 100%. Despite the small number of patients and the
short follow-up, preliminary results have shown very promising results.
PMID- 9638011
TI - Prognostic variables associated with implant failure: a retrospective
effectiveness study.
AB - The purpose of this study was to determine implant survival rates by means of
life table analyses for a cohort of patients not part of a prospective efficacy
trial and treated by practitioners at varying experience levels. Prognostic
variables associated with implant failure were identified by means of
proportional hazards models and advanced statistical methods that account for
patient effects. Ninety-nine consecutive patients treated from 1987 to 1991 with
follow-up to 1994 were included in this retrospective study. A total of 384
dental implants (79.7% Branemark, 19.3% IMZ plasma-sprayed, 1% IMZ hydroxyapatite
coated) were placed and subsequently supported 108 prostheses. Survival and
proportional hazards modeling were used to generate Kaplan-Meier survival curves
and to identify variables associated with implant failure. Survey data analysis
was used to adjust for any patient effects for variables identified as
significant through the proportional hazards models. Thirty-four implants failed
over the follow-up period (median follow-up time 3.6 years), resulting in an
overall failure rate of 8.9%. Seventeen of 99 patients experienced an implant
failure. When prosthesis type was excluded from the modeling process, survey data
analysis identified posterior location and an implant width of less than 4.0 mm
as being associated with implant failure (all P < .05).
PMID- 9638012
TI - Experience with osseointegrated implants placed in irradiated tissues in Japan
and the United States.
AB - A survey was undertaken to analyze osseointegrated implants placed in irradiated
maxillae and mandibles. It was found that nine centers in Japan and two centers
in the United States had placed 228 implants in 44 patients. Of 228 implants, 59
were placed in the maxilla, 169 in the mandible. Three of 169 implants placed in
irradiated mandibles were removed; 17 of 59 were removed from maxillae. One
hundred nineteen implants were placed in the mandible without adjunctive
hyperbaric oxygen treatment, of which only 2 were removed. From these results, it
is suggested that osseointegrated implants can be placed in the irradiated
mandibles of selected patients without hyperbaric oxygen treatment.
PMID- 9638013
TI - Prosthetic treatment using an osseointegrated implant after secondary bone
grafting of a residual alveolar cleft: a case report.
AB - Conventionally, for dental reconstruction after bone grafting of the congenital
residual alveolar cleft, a fixed prosthesis or removable partial denture is used.
In this paper, residual alveolar cleft reconstruction with an osseointegrated
implant following secondary bone grafting is described. The patient underwent
secondary bone grafting of the residual alveolar cleft at the age of 18 years.
One osseointegrated implant was placed in the bone bridge 8 months after bone
grafting. No problems up to 1 year after the fabrication and placement of the
fixed prosthesis have been observed.
PMID- 9638014
TI - Comparative study of guided bone regeneration using absorbable and permanent
barrier membranes: a histologic report.
AB - In an experimental study using the Gottingen minipig, Gore-Tex, Gore Resolut, and
Vicryl barrier membranes were tested for their efficacy in guided bone
regeneration. The results were compared to those of autologous periosteum. The
strongest reossification was seen in the bone defects covered with Gore-Tex;
however, time-dependent disintegration phenomena, which had already been observed
in preliminary examinations, were clearly established. After investigations of
cell cultures to which human macrophages were added, the latter findings can be
interpreted as the result of a physicochemical process, since a direct attack by
the macrophages was not seen in vitro. Of the membranes used, the absorbable ones
tended to collapse, depending on the size of the defect that was used, and they
did not enhance reossification as much as did the permanent membranes. The
periosteum-covered defects showed a satisfactory degree of regeneration, and no
differences were observed between freely transplanted and pedunculate periosteum.
PMID- 9638015
TI - Immediate implants placed into infected sites: a histomorphometric study in dogs.
AB - The study the effect of chronically infected sites on the immediate placement of
implants, periapical lesions were induced in the third and fourth premolars of
four dogs and the contralateral teeth were used as controls. Nine months after
the induction of periapical lesions, experimental and control teeth were
extracted, and 28 IMZ implants were immediately placed. After a healing period of
12 weeks, the animals were sacrificed, the hemimandibles were removed, and
specimens were prepared to be hard-sectioned and stained with toluidine blue. All
areas healed without inflammation or exudation and all implants were clinically
immobile and were radiographically determined to be surrounded by normal
appearing bone. Histologically, there were no signs of infection, and the
histomorphometric analyses revealed that 28.6% and 38.7% had osseointegrated for
the experimental and control implants, respectively. The difference was not
statistically significant. It was concluded that chronically infected sites, such
as those showing signs of periapical pathosis, may not be a contraindication for
immediate implants, if certain clinical measures and preoperative and
postoperative care are taken.
PMID- 9638016
TI - Minimally invasive diagnosis and surgery in breast screening.
PMID- 9638017
TI - Feasibility of population based screening in Ireland.
AB - Population registers have formed the basis for computerised call/recall registers
for screening programmes in many countries and have been important in achieving
high uptakes in targeted populations. The absence of a population register for
the ECCLES (European Campaign against Cancer, Localisation, Evaluation &
Screening) Breast Screening Project necessitated the development of a special
register of women in the target age group. The data sources used to build the
project register were the Eastern Health Board and North Eastern Health Board
General Medical Services database, Voluntary Health Insurance data and self
registration with the project. The register captured 86.3 per cent of the target
population. A debate on the merits and difficulties associated with the setting
up of a population register in Ireland is now timely.
PMID- 9638018
TI - Post herpetic neuralgia: a review.
PMID- 9638019
TI - Transport of digested decontaminated sputum specimens to a central laboratory for
testing for M. tuberculosis by Amplicor MTB test.
AB - Rapid diagnosis of tuberculosis may improve management of infected patients and
facilitate infection control procedures. The relatively slow growth rate of M.
tuberculosis and the limited sensitivity and specificity of microscopy make rapid
diagnosis difficult. Nucleic acid amplification techniques have been extensively
studied for the detection of M. tuberculosis DNA and a number of commercial
products for detection of M. tuberculosis nucleic acid in clinical specimens are
now available. As performance of diagnostic PCR at central reference laboratories
may be desirable, the impact of specimen transport on the performance of the
Amplicor MTB PCR assay is of practical importance. We have assessed the
performance of the Amplicor MTB PCR on specimens submitted and initially
processed in laboratories in 3 cities and then transported to a single laboratory
for PCR assay. The overall sensitivity of the PCR test was 97 per cent and the
corrected specificity was 100 per cent. All of 23 culture positive specimens
collected locally were PCR positive compared with 10 of 11 culture positive
specimens transported from elsewhere. In this study transportation of digested
decontaminated specimens to a central laboratory either frozen at -20 degrees, or
overnight at room temperature had no apparent effect on the performance
characteristic of the Amplicor MTB PCR assay.
PMID- 9638020
TI - Acquired von Willebrand's disease.
AB - von Willebrand's disease (vWD) is the commonest inherited bleeding disorder in
man with an estimated incidence of 1 per thousand of the population. Acquired von
Willebrand's disease (AvWD) is rare with less than 70 cases reported. AvWD is
usually associated with autoimmune or clonal proliferation disorders and whilst
the precise mechanism of acquired deficiency of von Willebrand factor (vWF) is
poorly understood, the most likely candidate mechanism(s) are; antibodies
inactivate or form a complex with immunologic or functional sites on vWF, or vWF
multimers are selectively absorbed by malignant cells. Unlike hereditary vWD, the
acquired form of the disease can be exceedingly difficult to manage. We report 4
cases of AvWD diagnosed at our centre over the past 3 yr. There was no evidence
of a previous personal or family history of bleeding in any of the patients and
AvWD was confirmed by laboratory testing. All 4 patients had a recognised primary
medical condition known to be associated with AvWD (Waldenstrom's
Macroglobulinaemia in 2 patients, hypothyroidism in 1 patient and monoclonal
gammopathy of unknown significance (MGUS) in 1 patient). The acquired haemostatic
defect corrected following treatment of the primary condition in 3 patients with
the other patient requiring on demand von Willebrand Factor replacement to
control spontaneous and surgery induced bleeding.
PMID- 9638021
TI - Role of carbon fibre implants in osteochondral defects of the knee.
AB - Articular cartilage defects of the knee are a common condition diagnosed at
arthroscopy. The management of these osteochondral lesions is controversial. We
present our experience using carbon fibre implants to repair these defects in 18
patients. Eleven patients (61 per cent) had an osteochondral defect of the medial
femoral condyle. Two patients had isolated patellar defects. The mean knee
assessment and functional scores were 75 and 80 respectively using The Knee
Society Clinical Rating System. Serial post-operative M.R.I. scanning revealed
that there was no loss of implant position with an extensive local tissue
response and good joint congruity. Overall, 11 patients (61 per cent) returned to
their normal sporting activity, while 3 patients (18 per cent) had a poor result.
One of these underwent a patellectomy. We conclude that carbon fibre implants may
have a role to play in the management of osteochondral defects of the femoral
condyles.
PMID- 9638022
TI - Uncensored open access gastroscopy--limited resources--unlimited demand.
AB - In the first 3 yr of an uncensored open access gastroscopy service in a County
Hospital, 891 patients attended for first gastroscopy. The data on these patients
is presented and compared with a randomly selected group who attended for
gastroscopy in the yr prior to the establishment of the service having come to
the normal Consultant clinics. In the open access group the gastroscopy
examination was normal in 29 per cent (32 per cent comparator group), 31 per cent
had major abnormalities (33 per cent comparator group) and 40 per cent had minor
abnormalities (35 per cent comparator group). Delay time from referral to
endoscopy was 37 days for open access patients (45 days comparator group). Only 6
per cent of open access patients were brought back to O.P.D. (47 per cent
comparator group) and 72 per cent of open access patients returned directly to
their family doctor (28 per cent comparator group). A comparison of the Clonmel
findings with British centres reporting their results shows a broadly similar
picture. It is concluded that almost 1,300 unnecessary clinic visits were avoided
by the provision of the open access service, some reduction in delay time to
gastroscopy was achieved, the family doctor maintained control of patient
management in the great majority of patients, the pattern of referral was not
inappropriate and compared very well with the comparator group. Over the 3 yr
there was a large increase in the number of gastroscopies performed which caused
resource difficulties. It is recommended that adequate planning of these
requirements should be carried out before an open access service is started. At
least 1 additional dedicated gastroscopy only endoscopy service per week would be
required.
PMID- 9638023
TI - The benefit of lowering cholesterol: relative risk can be absolutely misleading!
PMID- 9638024
TI - Epidemiology of hepatitis E virus in male blood donors in Jeddah, Saudi Arabia.
AB - To our knowledge, only a few epidemiological reports on the prevalence of
hepatitis E antibodies in Saudi blood donors have been published. Men of several
nationalities, donating blood at King Khalid National Guard Hospital (Jeddah,
Saudi Arabia) were selected (n = 593) for this study examining the seroprevalence
of hepatitis E virus (HEV) in the local male donor population and testing the
relationship of the antibody to HEV (anti-HEV) to donor characteristics using
Odds Ratio (OR) and Chi-square statistic. The prevalence of anti-HEV in the group
examined was 16.9 per cent (100/593). The seroprevalence for Saudi donors was
14.8 per cent compared with 33.3 per cent for non-Saudis of Middle Eastern
origin. Donors who were 40 yr and over had significantly higher seroprevalence
than those donors who were 30 yr or younger (OR = 2.5, p = 0.006). There was a
significant association between anti-HEV and anti-HCV with donors who were
positive to anti-HCV having about 5 times the risk of HEV than those who were
anti-HCV negative (p = 0.02). These findings demonstrate the high seroprevalence
rate of anti-HEV among male blood donors in Saudi Arabia.
PMID- 9638025
TI - Exaggerated blood pressure response to exercise: pathophysiologic mechanisms and
clinical relevance.
AB - The assessment of blood pressure during bicycle ergometry or treadmill exercise
is considered of paramount importance in establishing the eligibility of an
athlete to enter competitive sports. One of the potential risks related to an
exaggerated blood pressure response to stress testing is that in the long run
repetitive blood pressure peaks triggered by physical activity may determine
chronic target organ damage or favour the occurrence of an acute cardiovascular
event. Our concern should be addressed particularly to the competitive athlete,
insofar as training seems to increase the blood pressure reactivity to dynamic
exercise. However, studies performed in young borderline hypertensive subjects
have demonstrated that blood pressure level during steady-state long lasting
exercise can not be predicted by the maximum blood pressure attained during a
short-lasting incremental effort. Several prospective studies have demonstrated
that excessive increases in blood pressure during exercise may be a marker of
future sustained hypertension and of increased risk of cardiovascular mortality.
The steeper rise in exercise blood pressure in normotensive subjects prone to
develop hypertension and its complications seems to be due to a failure to reduce
total peripheral resistance adequately during exercise, as a result of initial
structural vascular changes which would pre-date the tonic elevation in the blood
pressure.
PMID- 9638027
TI - Ultra-triathlon-related blood-chemical and endocrinological responses in nine
athletes.
AB - BACKGROUND: Objective of this study was to get more insight in hematology,
biochemistry, and endocrinology of ultra-endurance exercise, to improve knowledge
in this field, supplementation, and medical care of affected athletes. METHODS: A
large body of individual hematological, biochemical, and endocrinological
parameters was analyzed in the blood taken from ultra-athletes before and after
completing the 1993 Colmar ultra triathlon covering 7.5 km swimming, 360 km
cycling, and approximately 85 km running. PARTICIPANTS: Nine experienced ultra
athletes participated in the study. A follow-up was not possible since the
athletes left Colmar within 24 hrs after the contest. RESULTS: The athletes
finished the ultra-contest at rankings 4, 5, 7, 8, 9, 11, 18, 22, 23 in a total
time between 23:38:53 and 27:54:30 hr:min:sec. Their final body mass (68.6 +/- 1
kg) was significantly lower than at baseline (71.9 +/- 4.2 kg). Non of the
athletes made use of medical care. Data after this contest reflect mild
hyponatremia, intravascular hemolysis, increased triglyceride turnover, acute
phase reaction, hyperaldosteronemia 2061 +/- 1013 pmol.L-1), hypercortisolemia
971 +/- 486 nmol.L-1), hyper-growth-hormonemia (median 6.8 ng.ml-1),
hypoinsulinemia, hypo-free-testosteronemia (42 +/- 17 pmol.L-1), protein
catabolism, depressed testicular function, oliguria, and muscle cell leakage.
CONCLUSIONS: In our opinion, data presented do not reflect any acute health risks
in healthy athletes who are well prepared and carefully supplied during such a
contest.
PMID- 9638026
TI - Effects of prolonged strenuous endurance exercise on plasma myosin heavy chain
fragments and other muscular proteins. Cycling vs running.
AB - BACKGROUND: This study evaluates creatine kinase, myosin heavy chain, and cardiac
troponin blood levels following three types of exercise: 1) short-distance uphill
or downhill running; 2) alpine ultramarathon; and 3) alpine long-distance
cycling. METHODS: EXPERIMENTAL DESIGN: Comparative field study; follow-up up to
10 days. SETTING: Department of Sports Medicine. All biochemical markers were
analysed at the Department of Medical Chemistry and Biochemistry. PATIENTS OR
PARTICIPANTS: Subjects included healthy, trained males (N = 53). All subjects
were nonsmokers and free from medication prior to and during the study. Each
volunteer was an experienced runner or cyclist, who had at least once
successfully finished the Swiss Alpine Marathon of Davos or the Otztal
Radmarathon before. INTERVENTIONS: Running or cycling. MEASURES: Plasma
concentrations of creatine kinase, myosin heavy chain fragments and cardiac
troponins were measured to diagnose skeletal and cardiac muscle damage,
respectively. RESULTS: Skeletal muscle protein release is markedly different
between uphill and downhill running, with very little evidence for muscle damage
in the uphill runners. There is considerable muscle protein leakage in the
ultramarathoners (67 km distance; 30 km downhill running). In contrast, only
modest amounts of skeletal muscle damage are found after alpine long-distance
cycling (230 km distance). CONCLUSIONS: This study proves that there is slow
twitch skeletal muscle fiber damage after prolonged strenuous endurance exercise
and short-distance downhill running. Exhaustive endurance exercise involving
downhill running and short-distance downhill running lead to more pronounced
injury than strenuous endurance exercise involving concentric actions. From our
results there is no reason for suggesting that prolonged intense exercise may
induce myocardial injury in symptom-less athletes without cardiac deseases.
PMID- 9638028
TI - Changes in plasma volume following intense intermittent exercise in neutral and
hot environmental conditions.
AB - BACKGROUND: The purpose of the present investigation was to examine the effect of
supramaximal short duration intermittent exercise in neutral and hot
environmental conditions on changes in plasma volume. The return of plasma volume
(PV) to pre-exercise values following different recovery conditions was also
examined. METHODS: Experimental design. Within subject design in which one way
analysis of variance was conducted. SETTING: Research, sports science academic
institute. PARTICIPANTS: Ten trained men, 25.5 +/- 3/1 (yrs), volunteers.
INTERVENTIONS: Subjects performed six 1-min bouts of exercise at 100% VO2peak on
a cycle ergometer, with 4-min rest intervals between the bouts. Each subject
exercised twice in thermoneutral (22 degrees C, 40% RH) and twice in hot (35
degrees C, 30% RH) conditions. Exercise was followed by either 40 min of passive
recovery (sitting) or by 20 min active recovery (cycling at 35% VO2peak) and 20
min passive recovery, named thereafter "active recovery". MEASURES: Hematocrit
(Hct) and hemoglobin (Hb) were determined upon entry into the climatic chamber
following 20 min rest in the chamber (pre-exercise), immediately postexercise,
and 40 min postexercise. From the changes in Hct and Hb, PV changes were
calculated. RESULTS: There was a significant decrease in PV immediately
postexercise. However, there was no significant difference between the two types
of environmental conditions and no difference between the two types of recovery.
PV increased significantly following recovery and returned to pre-exercise values
following 40 min of recovery. CONCLUSIONS: Changes in PV caused by maximal short
duration cycling bouts is not affected by environmental conditions, PV returns to
its pre-exercise values within 40 min of recovery regardless of the recovery
mode.
PMID- 9638029
TI - Comparison of the aerobic contributions to Wingate anaerobic tests performed with
two different loads.
AB - BACKGROUND: The purpose of the present study was to compare the aerobic
contribution of the Wingate anaerobic test by increasing the test load and power
output. METHODS: SETTING: The study was performed in the Physiology Department
of the Faculty of Medicine, Selcuk University. PARTICIPANTS: Thirty sedentary
male university students volunteered to this study. EXPERIMENTS: The subjects
performed two Wingate tests against resistance of 75 g.kg-1 and 95 g.kg-1 body
weight on Monark 818E bicycle ergometer. Breath-by-breath oxygen consumption
rates were measured using an automated metabolic measurement chart (Sensormedics
2900). Aerobic contribution was determined by dividing energy equivalence of net
oxygen consumption to the total work. RESULTS: The mean total work values
obtained from tests performed at 75 g.kg-1 and 95 g.kg-1 loads were 13.9 +/- 1.5
kjoules and 14.5 +/- 1.8 kjoules (t = 2.32, p = 0.03). Mean total oxygen
consumptions were 765 +/- 105 ml and 770 +/- 110 ml, respectively (t = 0.24, p =
0.81). Assuming 20% mechanical efficiency for both tests, aerobic contributions
were calculated as 19.5 +/- 3.7% and 18.9 +/- 3.7%, respectively (t = 1.01, p =
0.30). CONCLUSIONS: Although the power outputs of the two tests were different,
the difference between aerobic contributions was not statistically significant.
So, it was failed to say that the increase in the power outputs might be related
to higher contribution of anaerobic processes. However, if different mechanical
efficiencies could be used, relationship between aerobic contributions of two
tests might have been different.
PMID- 9638030
TI - The use of a fixed value of RPE during a ramp protocol. Comparison with the
ventilatory threshold.
AB - BACKGROUND: The purpose of our investigation was to assess the use of a fixed
value (12-13) of the Rating of Perceived Exertion (RPE) scale (6-20) as a valid
method for the determination of the workload corresponding to the ventilatory
threshold (VT) during a ramp protocol on a cycle ergometer. METHODS: Eleven
trained cyclists (22 +/- 3 years of age; VO2max: 65.2 +/- 12.4 ml.kg-1.min-1)
were selected as subjects. DESIGN: Each of the subjects performed a ramp protocol
on a cycle ergometer (starting at 25 W, with increases of 25 W.min-1 until
exhaustion). Gas exchange data were analysed continually during the test to
detect the ventilatory threshold (VT) of the subjects. In addition values of RPE
were obtained from each subject in the last 15 sec of each 2-minute-interval
during the tests, and immediately after exhaustion. The RPE threshold (RPET) was
defined as a constant value of 12-13. Mean values of VT and RPET were expressed
as VO2 (ml.kg-1.min-1), %VO2max, heart rate (bpm) and power output (W), and were
compared using a paired "t"-test. RESULTS: No significant difference (p < 0.05)
was found between mean values of VT and RPET, when both parameters where
expressed either as VO2, %VO2max, heart rate, or power output. CONCLUSIONS: In
conclusion, a fixed value (12-13) of the RPE scale might be used to detect the
exercise intensity corresponding to VT. Such parameter may therefore be used for
exercise prescription in substitution to more sophisticated methodologies.
PMID- 9638031
TI - Blood lactate concentrations during exercise: effect of sampling site and
exercise mode.
AB - BACKGROUND: The purpose of the study was to compare blood lactate concentrations
determined in blood sampled from three sites (finger capillary, ear-lobe
capillary, and forearm vein) during exercise on three different ergometers (a
cycle ergometer, a treadmill and an arm-crank ergometer). METHODS: A total of 312
well-trained subjects performed either a six-minute steady-state exercise (n =
219) or an incremental exercise test until exhaustion (n = 93). Blood was sampled
from two sites after each exercise test and at the end of each stage of the
incremental protocol, 852 pairs of blood samples were analysed. RESULTS: Results
showed that, when exercise was performed on a cycle ergometer or a treadmill, no
significant differences between venous and ear capillary samples were observed
whereas finger capillary values were higher. On an arm-crank ergometer, venous
and finger capillary lactate concentrations were usually higher than ear
capillary values with some discrepancies depending on the times of sampling.
CONCLUSIONS: We conclude that lactate values may differ depending on the sampling
site and the type of exercise mode. An ear capillary sample may be preferred
because it is less affected by lactate release in the arms and easier to obtain.
PMID- 9638032
TI - Identifying the integrated electromyographic threshold using different muscles
during incremental cycling exercise.
AB - BACKGROUND: The purpose of this study was to identify the IEMG threshold in the
vastus lateralis (VL) and rectus femoris (RF) muscles during progressive,
incremental exercise and to relate these thresholds to the ventilatory threshold
(Tvent). METHODS: Ten men (age: 23.40 +/- 3.13 yrs, mass 76.64 +/- 8.13 kg, %
fat: 8.81 +/- 2.32, VO2peak: 66.37 +/- 10.61 ml.kg.min-1) with cycling experience
completed a graded exercise test on a cycle ergometer by cycling at 90 rpm using
45 watt increments at two minute intervals. Oxygen uptake was measured
continuously and the IEMG activity of the VL and RF was calculated during the
last 5 s of each minute. The mean for the IEMG of 6 to 7 complete pedal
revolutions was used as the final value. Tvent was visually identified using the
VE/VO2 and V-slope methods. The IEMG threshold for VL and RF was visually
identified at the inflection point where a non-linear increase in IEMG occurred.
Comparisons between Tvent and IEMG thresholds were made using dependent means "t"
tests. RESULTS: Results showed that an IEMG threshold was identified in all 10
subjects for the RF, but in only 5 of 10 subjects for the VL. However, when
identified, the IEMG threshold for VL was similar to RF.VO2 at IEMG threshold for
RF (3.53 +/- 0.36 L.min-1) was not significantly different from Tvent (3.36 +/-
0.42 L.min-1). CONCLUSIONS: These results show that the IEMG threshold is more
consistently detected in the RF compared to VL during incremental cycling
exercise. In addition, the IEMG threshold for RF was closely related to Tvent and
provides an alternative means to assess the ventilatory threshold.
PMID- 9638033
TI - Caffeine consumption habits do not influence the exercise blood pressure response
following caffeine ingestion.
AB - BACKGROUND: The purpose of this study was to determine if the BP response during
walking following caffeine ingestion differed between those who regularly consume
caffeine and those who do not. METHODS: A double-blind cross-over experimental
design was used. Data were collected in a research laboratory with a clinical
exercise testing room. Eight regular caffeine users and eight men who did not
habitually consume caffeine were studied. Each subject consumed of a beverage
once with and once without 4.5 mg caffeine/kg fat-free mass added to the drink.
Following consumption each subject walked at three intensities of exercise (30,
50, and 70% of VO2peak). Measures of BP were obtained by the auscultatory
technique. RESULTS: Caffeine consumption resulted in significant increases in
both systolic BP and diastolic BP at rest and during exercise. The elevation
during exercise was 7-8 mmHg at all three exercise intensities for systolic BP;
however, for diastolic BP there was only a significant elevation (4 mmHg) at the
highest exercise intensity. No differences were noted between those men who
regularly consume and those who regularly abstain from caffeine. There was a wide
range in the resting BP response to caffeine (combined SBP and DBP ranged from 10
39 mmHg) suggesting that there are marked differences in sensitivity to caffeine,
irrespective of individuals' consumption habits. CONCLUSIONS: Consideration
should be given to caffeine intake prior to exercise in patients for whom an
additional increase in BP during exercise would not be desirable.
PMID- 9638034
TI - Exercise tolerance, body composition and blood lipids in obese African-American
women following short-term training.
AB - BACKGROUND: The purpose of this investigation was to examine the exercise
tolerance, body composition and blood lipids in African-American women,
possessing greater than or equal to 30% body fat, following six weeks of
endurance training. METHODS: Oxygen consumption (VO2), central hemodynamics,
blood lipids, body weight, body fat, and the body mass index of seven subjects
(21.0 +/- 0.8 yrs) were studied. Heart rate (HR), blood pressure (BP), exercise
duration, rating of perceived exertion (RPE), blood lactate (bLA) and VO2 were
obtained in response to a maximal exercise tolerance test on a motorized
treadmill. Subjects trained three times per week for 50 minutes per session (30
minutes at 70% maximal oxygen consumption (VO2max). RESULTS: Dependent "t"-tests
revealed significant (p < 0.05) increases in VO2max, 27%; exercise duration, 31%;
as well as peak HR, systolic blood pressure (SBP), and bLA. Values for submaximal
HR, SBP, RPE during the post-training test were lower. In addition, body weight,
body fat and the body mass index decreased 2.2%, 1.3% and 3.4% respectively.
There were no changes in blood lipids. CONCLUSIONS: These findings suggest short
term training at 70% VO2max provides the necessary stimulus for obese women to
improve exercise tolerance and body composition. However, the training stimulus
is insufficient to alter lipid profiles.
PMID- 9638035
TI - Measurement of exercise dependence in bodybuilders.
AB - OBJECTIVE: The purpose of this study was to explore exercise dependence in
bodybuilders, and undertake preliminary validation of a measurement instrument.
EXPERIMENTAL DESIGN: A comparative analysis of self-report indices between
groups. PARTICIPANTS: Forty-seven bodybuilders, 31 individuals who weight trained
for general fitness purposes and 24 weightlifters participated in the study.
MEASURES: Each subject completed the following: demographic information,
bodybuilding-specific versions of the social identity and exclusivity scales of
the Athletic Identity Measurement Scale, the physical strength and body
attractiveness subscales of the Physical Self-Perception Profile, a short form of
the Marlowe-Crowne Social Desirability Scale, and a 9-item Bodybuilding
Dependence Scale. RESULTS: Factor analysis on the BDS revealed 3 subscales
(social dependency, training dependency and mastery) which accounted for 68.4% of
the variance. Internal consistency was satisfactory for each subscale
(Chronbach's alpha = 0.76, 0.75 and 0.78 respectively). The BDS social dependency
and PSPP body attractiveness scores of the bodybuilders were higher than those of
the weightlifters, whose scores were higher than those of the fitness trainers.
The bodybuilders scored higher on both AIMS subscales than the other groups. The
bodybuilders and weightlifters scored higher on PSPP physical strength than the
fitness trainers. BDS social dependency correlated with both AIMS and both PSPP
subscales, and BDS training dependency correlated with AIMS exclusivity. All
three BDS subscales correlated with training frequency. Discriminant analysis
found the combination of AIMS social identity, BDS social dependency and years
training experience enabled correct classification of 92% of the respondents.
CONCLUSIONS: These results support the construct and concurrent validity of the
BDS social dependency subscale, but do not wholly support the validity of the
other two subscales.
PMID- 9638036
TI - Training and injuries amongst elite female orienteers.
AB - BACKGROUND: A study was carried out on the patterns of injury amongst elite
female orienteers. METHODS: A retrospective questionnaire was administered which
contained questions pertaining to training practices such as quality, quantity
and type. This was followed by a section investigating general to specific injury
problems, regarding their occurrence and effect on training. Members of various
national orienteering squads (elite group; n = 19) and competitors of an elite
level in Great Britain (sub-elite group; n = 9) completed these questionnaires.
As this was a descriptive study, no intervention was carried out. RESULTS: The
sub-elite orienteers trained less than the elite during the off-season (p < 0.01)
but there was no significant difference in the distribution and/or likely cause
of injuries between the groups. Only 32% of the subjects did their training
predominantly on the road while the others ran on either off-road terrain or a
mixture. Injuries occurred in 68% of the respondents. Only 4% of them suffered
upper body injuries. Ankle injuries were the most common injuries. The proportion
of injuries to the knee (16%) and ankle (43%) in orienteers was the reverse of
what is normally found in runners. CONCLUSIONS: Orienteers suffer certain sport
specific injuries such as ankle sprain. This is likely to be related to their
training predominantly on rough surfaces.
PMID- 9638037
TI - Overweight prevalence in persons with Down syndrome.
AB - Prevalence of overweight among the general population has been reported to be 33%
for males and 36% for females. We undertook this study to establish overweight
prevalence data in a cohort with Down syndrome and to stratify the incidence of
overweight by living arrangement. We measured Body Mass Index (BMI) in 283
persons with Down syndrome and found a higher prevalence of overweight in this
group compared to the general population. Individuals with Down syndrome living
in a family setting had a higher incidence of overweight than did those living in
a group home setting. Overweight prevalence among persons with Down syndrome
should be considered a major public health concern that warrants further
attention from researchers, practitioners, family members, and individuals with
Down syndrome.
PMID- 9638038
TI - Neuroleptic-induced dementia documented in four adults with mental retardation.
AB - This is the first report to my knowledge of neuroleptic-induced dementia in
adults with mental retardation. Four adults showed full recovery after having
significant cognitive deterioration that persisted until the offending medication
was withdrawn. The ages at onset of dementia were 37, 37, 39, and 55 years; the
duration of dementia ranged from .5 to 2.5 years. Three adults had Down syndrome
and one had mental retardation due to an unknown cause. The neuroleptic-induced
dementia occurred while the individuals were on a low dose of either loxapine,
thioridazine, haloperidol, or pimozide.
PMID- 9638039
TI - Evaluation of outcomes and cost-effectiveness of a community behavioral support
and crisis response demonstration project.
AB - A behavioral support and crisis response demonstration project authorized by the
Minnesota Legislature in 1992 was evaluated. We described the demonstration
program, its service users, and satisfaction and concerns with the program of
service recipients, their families and careproviders, and county case managers.
We also provided follow-up data on the outcomes of the first year service users
and gave the service outcomes projected by case managers had the program not been
established. These projected outcomes were validated by follow-up of a comparison
group of persons unable to access the program's services. Cost-effectiveness was
computed from costs of establishing and operating the demonstration program and
the actual average costs of the services that were projected to otherwise have
been used.
PMID- 9638040
TI - Effects of video-based staff training with manager-led exercises in residential
support.
AB - The effectiveness of video-based staff training with manager-led exercises in
improving staff performance in residential support for persons with disabilities
was examined. Research staff assisted two residential program managers to
implement staff training in health and safety, basic support, and residential
support values. Results showed improvement in (a) staff members' washing hands
when appropriate, (b) wearing gloves when appropriate, and (c) frequency of
positive interactions with residents. These changes in staff behavior maintained
over a 6-month follow-up. Following the values training, in one house, brief
increases were observed in frequency of residents' community activities. These
changes did not maintain. No improvements in these measures were noted in the
other house. Implications of these findings for assurance of competent staff
performance with residents were discussed.
PMID- 9638041
TI - Employment outcomes for people with severe disabilities: opportunities for
improvement.
AB - Supported employment began with a focus on those individuals deemed less likely
to secure a job in the community: those with severe mental retardation,
behavioral challenges, and multiple disabilities. The creation of supported
employment resulted, in part, because of demonstrations of the competence and
capabilities of these same people previously thought to be unemployable in any
meaningful sense of the word. However, as supported employment has unfolded,
those with the most severe disabilities appear to be underrepresented in the
ranks of those benefitting from supported employment. Although the limited access
to supported employment by individuals with such labels appears clear, little is
known about how the employment of those with more severe disabilities compares
with others in supported employment. This report provides analyses of the
employment features, support patterns, and outcomes for persons with more severe
disabilities in supported employment.
PMID- 9638042
TI - How a regression artifact makes ICFs/MR look ineffective.
AB - Based on a simple matched-control group quasi-experiment, Conroy (1996) concluded
that small ICFs for persons with mental retardation have negative quality-of-life
impacts. Our analysis of Conroy's design suggests, in contrast, that the reported
effect is a pure regression artifact. The flaw in Conroy's design is selecting a
control group on the basis of pretest matching. Although selecting a subsample of
controls by matching on static characteristics such as age or gender can reduce
the confounding influence of these variables, selection on the basis of pretest
scores leads invariably to a large, spurious effect. The literature on this issue
dates back a century, with warnings against pretest matching by Galton,
Thorndike, McNemar, Stanley, Campbell, Cronbach, and Cook. We reviewed this
historical literature and then used a Monte Carlo experiment to estimate the
spurious effect that Conroy would observe from pretest matching alone. The
magnitude of the artifact is as large as the quality-of-life reduction that
Conroy attributed to the effects of living in an ICF. We discussed the
methodological logic involved in matching and the broader policy issues raised by
this evaluation.
PMID- 9638043
TI - Break the data-bank with Monte Carlo? Statistical problems in the dispute between
Conroy (1996) and Crinella, McCleary, and Swanson (1998)
AB - In drawing entirely different conclusions from the same bank of data, Conroy saw
consistent evidence favoring the alternative CLAs over the small ICFs in
Pennsylvania while Crinella et al. found a large regression artifact produced by
matching the ICF and CLA residents on adaptive behavior scores. Ten areas of
flawed logic, analysis, and interpretation have undermined both sides of the
argument. Conroy's matching--which might not have been necessary in the first
place--does not pose a serious threat of regression artifacts. Because of two
subtle but fatal errors, the Monte Carlo experiment of Crinella et al. provides
no important evidence against Conroy's findings. Other problems, however, require
a small reduction in his pro-CLA results, along with a substantial limit on their
generalizability.
PMID- 9638044
TI - The Carrier Advisory Committee five years later.
PMID- 9638045
TI - Provider sponsored organizations.
PMID- 9638046
TI - Metastatic basal cell carcinoma of the auricle.
PMID- 9638047
TI - [Roller-skating injuries].
PMID- 9638048
TI - [Treatment of aortic aneurysm with endovascular stent graft].
PMID- 9638049
TI - [Total mesorectal excision in rectal cancer].
PMID- 9638050
TI - [Introduction of a new surgical technique in rectal cancer].
AB - Local recurrence rates following surgery for rectal cancer show considerable
variation in different series, but impressive results (< 4% local recurrences
after five years) have been presented by surgeons using total mesorectal excision
as their operative technique. In Norway, local recurrence rates of 30% have been
reported. Total mesorectal excision was introduced at Ullevaal Hospital in
January, 1994 following a specific training programme. To enable us to compare
the results, we followed-up two groups of patients who had undergone surgery for
rectal carcinoma; one group (76 patients) before the introduction of total
mesorectal excision and the other (76 patients) after total mesorectal excision
was introduced. Anastomotic leakages were the main problem in the initial phase,
but after faecal diversion became routine only one leakage was observed. After a
median observation time of 28 months we had observed two patients (4.3%) with
local recurrence in the total mesorectal excision group, and ten (23.8%) in the
group where total mesorectal excision had not been performed.
PMID- 9638051
TI - [Endovascular treatment of thoracic aortic aneurysm].
AB - Two patients with aneurysms of the descending thoracic aorta were treated by
endovascular technique. One of the patients was also treated for an infrarenal
aortic aneurysm by open surgery during the same procedure. The other patient had
chest pain, probably caused by an impending rupture. The procedures were
performed using fluoroscopy by a C-arm. The thoracic aneurysms were replaced by
an implant made of polyester where Z-stents had been applied on the inside. The
prosthesis was mounted on a pusher and advanced through an introducer. When a
proper position was obtained, the introducer was withdrawn, and the prosthesis
was deployed immediately below the left subclavian artery. Endovascular treatment
seems to represent a less traumatic procedure than open surgery. Both operations
were uncomplicated and both patients were followed up for more than six months.
No complications were observed. A longer follow-up period is necessary to
evaluate this treatment fully.
PMID- 9638052
TI - [Cholesterol values in a cohort of adolescents in Sor Trondelag].
AB - Over a four-year period total serum cholesterol values were obtained from all 7th
grade lower secondary school students (age 13) in a municipality in Norway. The
139 girls included in the survey had a mean value of 4.24 mmol/l (95% CI 4.12
4.37), and the 160 boys 4.11 mmol/l (95% CI 3.98-4.23), which is slightly lower
than other Nordic surveys. Some students from one year were also measured in the
9th and 11th grades. One student was found to have familial hyper
cholesterolemia, and this value was excluded from the reference material.
Screening for this disease among students is not recommended.
PMID- 9638053
TI - [Neuralgic amyotrophy or an isolated lesion of the anterior interosseal nerve?].
AB - In this article we describe five patients with acute or subacute weakness of
flexor pollicis longus and flexor digitorum profundus. A possible diagnosis of an
isolated lesion (entrapment) of the anterior interosseus nerve was considered.
However, clinical and neurophysiological findings suggested a diagnosis of
neuralgic amyotrophy. Three patients experienced acute shoulder pain at the
onset. Sensory loss at the base of the thumb was observed in two patients, and
two patients were affected bilaterally. All patients had EMG signs of involvement
outside the anterior interosseus nerve innervation area. Low amplitude sensory
action potentials were observed in three patients. One patient was operated upon
and entrapment was not observed during surgery. Reinnervation was not seen after
five months, but was noted in three patients who were investigated 13, 13.5, and
30.5 months after the onset. Thus, the prognosis in this unusual form of
neuralgic amyotrophy seems to be rather good, and the length of time before
reinnervation supports the theory that the site of the lesion must be located
proximally, e.g. in the brachial plexus.
PMID- 9638054
TI - [Postoperative tetanus after gangrenous ileus].
AB - Tetanus has become an uncommon disease in developed countries. Tetanus is caused
by exotoxins from the bacteria Clostridium tetani. This microbe, which is
obligate anaerobe, is present in soil, and animal and human faeces. The condition
usually appears after contamination of wounds. However, reports have been
published of tetanus occurring after both acute and selective gastrointestinal
surgery. We present a case of severe postoperative tetanus in a 57 year-old woman
who underwent bowel resection after strangulation of the ileum. The patient was
treated on an intensive care unit and was artificially ventilated for 64 days.
Seven months later she had fully recovered. Clinical presentation, diagnosis,
treatment, and complications are discussed in the report. The diagnosis of
tetanus is made by clinical observation. Nowadays, lack of suspicion of this
condition may cause delay in administering proper treatment. Women and older men
are often inadequately immunized. Doctors should therefore examine the
immunization status of these groups of patients regularly.
PMID- 9638055
TI - [Iatrogen perforation of the rectum after colon radiography].
AB - Perforation of the rectum following barium enema is relatively rare, occurring in
1 of 3,000 procedures. Colorectal perforation is a serious condition and early
diagnosis is of paramount importance in order to avoid any delay in treating the
patient. Direct suture of the perforation, lavage, presacral drainage and stomia
are the preferred methods of primary surgical treatment.
PMID- 9638056
TI - [Mechanisms behind drug dependence].
AB - The neurobiological mechanisms involved in the development and maintenance of
drug dependency are reviewed and discussed. Whereas physical dependency is
related to abstinence symptoms with a noradrenergic hyperactivity in locus
ceruleus, motivational dependency is related to euphoria, which correlates with
dopaminergic activity in the mesolimbic pathway, especially in nucleus accumbens.
Despite the fact that many addictive drugs are chemically unrelated, they
increase the extracellular levels of dopamine in nucleus accumbens. This has been
observed with cocaine, amphetamine, ecstacy, nicotine, opiates, ethanol, and
cannabinoids. On the other hand, substances like LSD do not appear to influence
the dopamine level in the mesolimbic pathway. Increasing knowledge about how drug
abuse modulates signal pathways in discrete parts of the brain gives a new
insight into the development and maintenance of drug dependency.
PMID- 9638057
TI - [Hereditary cancer].
AB - A significant proportion of all cancers is inherited or develops in genetically
susceptible individuals. An updated overview and tabulations are given on
inherited cancer, including the monogenic cancer syndromes, cancer caused mainly
by predisposition in heterozygous carriers for autosomal recessive syndromes, and
the same of different types of cancers occurring in families exhibiting irregular
autosomal dominant inheritance. Environmental factors act in concert with
genetically susceptible genes to cause cancer. A mechanism for the initiation and
progression of cancer on the cellular level is outlined. The identification of an
ever-increasing number of cancer-susceptible genes enables the development of new
genetic tests. Some advantages and problems associated with predictive genetic
testing for cancer are discussed.
PMID- 9638058
TI - [Oncogenes--"reckless drivers" on signal pathways controlling cell division].
AB - Today, about 20 years after the discovery of cellular genes with oncogenic
potential, we possess substantial knowledge on the regulation of normal cell
growth and division. At the same time, we have gained insight into the loss of
growth control which occurs in cancer cells. The following is a brief review of
the progress made in oncogene research and the knowledge we have gained. It is
important to stress that our understanding of the cellular and molecular
mechanisms involved is still in its infancy. However, pieces are being added to
the puzzle at an increasingly faster pace, primarily because of the progress in
gene technology during the last two decades. Research methods have been set up to
allow greater cooperation across disciplinary boundaries, thus increasing the
speed with which important discoveries occur. A goal for the future will be to
identify all oncogenes and tumor suppressor genes and elucidate their functions.
At the same time, one of the major challenges will be to translate the knowledge
thus gained into the development of more powerful and specific therapeutic
strategies. As a result of the increasing insight gained by modern oncogene
research, the need for detailed cancer diagnostics based on molecular genetics
will increase significantly in the future.
PMID- 9638059
TI - [Tumor suppressors--genes and proteins].
AB - Cancer is generally understood to be a genetic disease in the sense that somatic
mutations are the cause of tumour initiation and development. Our knowledge of
cancer-associated genes and gene products has evolved mainly over the past 20
years. The identification and characterization of tumour suppressor genes (TSGs)
as normal growth-inhibiting or apoptosis-inducing genes have helped us to
understand how mutations are tumorigenic. Various TSG encoding membrane-, cytosol
, or nuclear proteins have been identified. Tumor suppressor genes are often
functionally inactive in cancer cells because of mutations of both parental gene
copies. Many TSGs are associated with hereditary cancer diseases or syndromes
caused by the existence of one mutant allele in the germ-line. Individuals who
carry only one functional gene copy, are therefore at great risk of developing
cancer. Several TSGs, such as TP53, RB1 and CDKN2A, encode proteins that are
significant to the cell cycle. TP53 is the most frequently mutated gene in human
cancer, showing changes in more than 50% of all solid tumours. Both DNA repair
and apoptosis are stimulated by p53-induced transcription of genes involved in
the two processes. The characterization of TSGs and their gene products has led
to the identification of a number of new diagnostic and prognostic molecular
genetic parameters in oncology. Furthermore, some TSGs are potentially among the
most promising and important targets for gene therapy in cancer and other
hyperproliferative diseases.
PMID- 9638060
TI - [We need a specialty of community and general psychiatry].
PMID- 9638061
TI - [Migraine and stroke].
PMID- 9638062
TI - [Medical findings].
PMID- 9638063
TI - [Hereditary hemochromatosis and use of genetic tests].
PMID- 9638065
TI - [Physicians and drug industry].
PMID- 9638064
TI - [What happened with the confidence intervals?].
PMID- 9638066
TI - Image is all but interpretation is the key.
PMID- 9638067
TI - The diagnosis of lameness associated with distal limb pathology in a horse: a
comparison of radiography, computed tomography and magnetic resonance imaging.
AB - A cadaver limb from an eight-year-old horse with right forelimb lameness that was
relieved with an intra-articular distal interphalangeal joint block was imaged
with radiographs, spiral computed tomography (CT) and magnetic resonance imaging
(MRI). Spiral CT demonstrated several lucencies within the deep digital flexor
tendon immediately proximal to the navicular bone. On MRI these areas had
increased signal and there was enlargement of the tendon at this site. Effusion
in the proximal interphalangeal joint and navicular bursa and thinning of the
fibrocartilage of the navicular bone were also observed on MRI images. These
changes were not detected on radiographs. Histopathology confirmed that there
were focal areas of collagen necrosis within the deep digital flexor tendon with
thinning and degenerative changes in the fibrocartilage of the navicular bone.
PMID- 9638068
TI - Isolation and identification of canine matrix metalloproteinase-2 (MMP-2).
AB - A canine gelatinase, with an apparent molecular mass of 62 kDa in non-reducing
zymography, is produced by fibroblasts, chondrocytes and a myelomonocytic cell
line. The enzyme has similar characteristics to human matrix metalloproteinase
(MMP) 2 and cross-reacts in Western blotting analysis with a sheep polyclonal
antiserum raised against human MMP-2. The 62 kDa canine protein was purified from
cell culture media, and the N-terminal amino acid sequence determined following
blotting on to a polyvinylidene difluoride (PVDF) membrane. The sequence was 87%
identical to that published for human MMP-2. We therefore consider this enzyme to
be canine MMP-2.
PMID- 9638069
TI - Use of recombinant human erythropoietin as adjuvant therapy for blood banking for
autotransfusion in dogs.
AB - Recombinant human erythropoietin (rhEPO) has been assessed for its potential
value as an adjuvant in the banking of blood for autotransfusion in dogs. Twelve
normal adult dogs were assigned to three groups (saline, iron, and iron plus EPO
groups). On day 0, day 3, and immediately after each autologous blood donation,
the first group received normal saline as a placebo, the second group received
4.1 mgkg-1 of iron (iron chondroitin sulphate), and the third group received 600
IU kg-1 of rhEPO in combination with 4.1 mgkg-1 of iron. Blood for autologous
donation equivalent to 10 mL kg-1 was collected from each dog on days 7 and 10.
The blood was retransfused on day 14 during the removal of an equal volume of
blood and the effect of the autotransfusion evaluated on day 17. After the
autologous blood donation, a marked decrease in haematocrit occurred in the
saline and iron groups. In contrast, the haematocrit remained virtually unchanged
in the iron plus EPO group indicating the therapeutic effect of rhEPO. The iron
plus EPO group also maintained a high haematocrit after blood collection if they
had been autotransfused first. It was concluded that rhEPO is a valuable adjuvant
in canine blood banking for autotransfusion.
PMID- 9638070
TI - A study of cattle-to-cattle transmission of Mycobacterium bovis infection.
AB - Twenty steers, positive to the single intradermal comparative tuberculin test
(SICTT), were selected from herds with a recent history of Mycobacterium bovis
infection. Ten steers, negative to SICTT, were selected from herds with no
history of M. bovis infection and served as in-contact animals. The animals were
divided into 10 groups, each consisting of two SICTT-positive (reactor) animals
and one in-contact animal. Each group was housed in an individual loose-box for a
period of 1 year. Five of the groups were fed a restricted diet for part of the
experiment. All cattle were slaughtered at the end of the study period and
examined at post mortem. Transmission of infection to an in-contact animal
occurred in four of the 10 groups. One of the four in-contact animals, which
became infected, had a retropharyngeal lymph node tubercle and M. bovis was
isolated from lymph nodes without visible lesions from the other three. Two of
the infected in-contact animals without visible lesions did not show any
detectable cell-mediated immune response. There was no evidence that dietary,
restriction had any effect on transmission of disease.
PMID- 9638071
TI - Bovine serum transferrin concentration during acute infection with Haemophilus
somnus.
AB - A novel, competitive immunoassay based on time-resolved fluorimetry was
developed, and used to measure the serum concentration of bovine transferrin
during acute Haemophilus somnus pneumonia. Upper and lower limits of normality
were established using serum from healthy cattle (3.72-1.37 mgmL-1). Following
experimental infection with Haemophilus somnus, transferrin concentration was
depressed in all calves but recovered to pre-infection levels in groups of calves
which had either no lesions, or mild lesions at necropsy between 5 and 6 days
after infection. In a third group, which developed extensive lesions, the
transferrin concentration remained depressed. Transferrin levels remained within
the normal range for all calves during the experimental period. Those calves
which had low transferrin concentrations pre-infection, developed extensive lung
lesions following experimental infection with Haemophilus somnus.
PMID- 9638072
TI - Equinins in equine neutrophils: quantification in tracheobronchial secretions as
an aid in the diagnosis of chronic pulmonary disease.
AB - Equinins are a closely related group of proteins found in equine neutrophil
granules. They demonstrate proteinase inhibiting activity restricted to microbial
proteinase K and subtilisin, and they also possess antibacterial and antiviral
properties. Antiproteinase K activity was measured in tracheobronchial secretions
(TBS) of horses with mild (n = 15), moderate (n = 30) and severe (n = 16) chronic
pulmonary disease, to determine its usefulness as an indicator of severity of
disease and to measure neutrophil content. Determination of proteinase K
inhibiting activity was based on a colorimetric assay measuring the suppression
of 4-nitroaniline liberation from the synthetic substrate succinyl-L-alanyl
alanyl-alanin-4-nitroanilid, a process mediated by proteinase K. Proteinase K
inhibiting activity proved to be a valid and simple indicator for assessing
neutrophil content in TBS and a useful parameter to determine the severity of
chronic pulmonary disease in the horse.
PMID- 9638073
TI - Detrimental effects on villus form during conventional oral rehydration therapy
for diarrhoea in calves; alleviation by a nutrient oral rehydration solution
containing glutamine.
AB - This paper examines the possibility that treatment of diarrhoea with conventional
oral rehydration solutions (ORSs) may be detrimental to villus structure by
imposing nutrient deprivation and that such detrimental effects may be reduced or
avoided by using a nutrient ORS. A conventional WHO-type ORS (W) was compared
with two nutrient solutions (N and G) both containing high glucose concentrations
and the latter containing glutamine; their effects on enteric structure were
assessed by morphometric analysis of samples obtained from diarrhoeic calves
after 96 h treatment. Comparisons were also made with samples from controls and
diarrhoeic calves at the stage where oral rehydration would have begun in the
treated groups. As in our previous ORS studies, diarrhoea was induced with
enterotoxigenic Escherichia coli (09:K30:K99). We measured villus length and
width, crypt depth and width and calculated villus surface area in proximal, mid
and distal small intestine (PSI, MSI, DSI), using standard morphometric
techniques. Proximal and distal spiral colon samples (PC, DC) were examined for
crypt depth and width; mitoses per crypt were counted in samples from all
regions. Non-diarrhoeic calves showed the expected gradient of villus length
through PSI, MSI and DSI, hence data for each region are normalized as a
percentage of the control value for that region. PSI showed the greatest loss of
villus length and surface area (50%) with diarrhoea. In MSI and DSI the villus
loss was greater with solution W and N or G, as were increased mitoses and crypt
depth. Crypt depth and mitoses also increased in the colon with solution W.
Colonic crypt width increased with diarrhoea and conventional oral rehydration
but less so with G; there is reason to believe that such changes have functional
significance. Crypt changes in colon, MSI and DSI were least with solution G. The
changes developing in diarrhoeic calves prior to treatment were thus less
apparent in those treated with a nutritional ORS, particularly if it contained
glutamine.
PMID- 9638074
TI - Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves:
evaluation in models of acute inflammation.
AB - Injections of mild irritants intradermally (carrageenan, zymosan and dextran) and
intracaveally (carrageenan) in a tissue cage model of inflammation were used in
studies of the pharmacodynamics and pharmacokinetics of tolfenamic acid
administered intramuscularly in calves. Inhibition of serum thromboxane (TX)B2
and inflammatory exudate prostaglandin (PG)E2 were used as indicators of the
magnitude and time course of blockade of cyclo-oxygenase isoforms COX-1 and COX
2, respectively. Single doses of 2, 4 and 8 mgkg-1 tolfenamic acid partially
inhibited irritant-induced rises in skin temperature (non-dose dependently) and
skin oedema (dose-dependently). These doses also markedly inhibited serum TXB2
synthesis and the duration of inhibition was dose-related. A dose of 2 mgkg-1
tolfenamic acid also attenuated skin temperature rise over carrageenan-injected
tissue cages, and markedly inhibited exudate PGE2 synthesis, even though drug
penetration into both exudate and tissue cage transudate was limited. Tolfenamic
acid pharmacokinetics were characterized by a relatively short tmax (0.94-2.04
h), a high estimated Vdarea (1.79-3.20 Lkg-1), an estimated t1/2 beta of 8.01
13.50 h and Cl beta of 0.142-0.175 Lkg-1h-1. The actions of tolfenamic acid in
inhibiting PGE2 synthesis and in attenuating two of the cardinal signs of
inflammation (heat and swelling) suggest that a dosage of 2 mgkg-1 administered
intramuscularly should be effective clinically as an anti-inflammatory agent.
PMID- 9638075
TI - Molecular analysis of the virulence determinants of Clostridium perfringens
associated with foal diarrhoea.
AB - During an epidemiological study of foal diarrhoea, over half of the cases yielded
Clostridium perfringens which was significantly associated with disease
(Netherwood et al., 1996b). However, the association could not be accounted for
by enterotoxigenic isolates which had a low prevalence (Netherwood et al., 1997).
Nonetheless, we have hypothesized that the association may be caused by a
pathogenic sub-population which would be significantly more common amongst C.
perfringens-positive cases compared with C. perfringens-positive healthy controls
if it acted as a pathogen when present. Conversely, if foal diarrhoea caused by
C. perfringens was dependent on a predisposing factor, then such an association
might not be evident. As a first step to determine if a molecular marker was more
frequently to be found in C. perfringens-positive cases than controls, we have
genotyped the study isolates (up to five per foal) by polymerase chain reaction
(PCR) based on the published gene sequences for the major lethal toxins alpha,
beta, epsilon and iota as well as for theta toxin, large and small sialidases,
hyaluronidase and virulence regulation. Isolates of major toxin types B, C, D and
E, or isolates which were untypeable, were isolated from less than 15% of C.
perfringens-positive foals and these were not associated with diarrhoea nor were
they more commonly found in C. perfringens-positive cases. Isolates of type A
were found in more than 90% of all C. perfringens-positive foals. A number of
different genotypes were identified by their different patterns of gene
possession but types without any of the genes for theta toxin, large and small
sialidases, hyaluronidase and virulence regulation were found in only 10% of
positive foals. Only type A isolates with all of these genes were associated with
diarrhoea overall but they were not more commonly isolated from C. perfringens
positive cases than controls. In conclusion, genotyping by the sequenced
virulence genes did not identify a marker for a sub-population of C. perfringens
which may be acting more frequently as a pathogen when present.
PMID- 9638076
TI - Plasma aspartate aminotransferase and creatine kinase activities in thoroughbred
racehorses in relation to age, sex, exercise and training.
AB - In order to investigate the effect of age, sex and month on the response of
plasma aspartate aminotransferase (AST) and creatine kinase (CK) to exercise,
blood samples were collected once a month between March and September from a
group of 40 2- and 3-year-old (2yo and 3yo) thoroughbred racehorses (kept under
the same managemental regimen) at rest before exercise (PRE) and at 2 (2H) and 24
h (24H) post-exercise. The absolute change in activities between the 2H and PRE
samples (2H delta) and the 24H and PRE samples (24H delta) was also calculated.
Age had a significant effect on all measured and calculated parameters for colts
(C), apart from 24H delta CK but showed no effect in the fillies (F). Sex only
had a significant effect in the 3yo in the 2H delta CK. In the 2yo, significant
effects of sex were found for both CK and AST in the PRE, 2H and 24H samples. The
effect of month varied according to the classification group with only the 2yoC
not showing any significant effect on any parameter. Fillies were, in general,
more likely than colts to show greater than a twofold increase in CK activity at
2H post-exercise and the number of animals showing such an increase decreased as
the season progressed. Very little change in AST activities occurred with
exercise.
PMID- 9638077
TI - Ultrasonographic examination of the ovine thorax.
PMID- 9638078
TI - Effect of single and divided dose administration on the pharmacokinetics of
albendazole in sheep and goat.
AB - The pharmacokinetics of albendazole were studied in sheep and goats following
single and divided dose administration at nematocidal and flukicidal dose rates.
The disposition curves of the metabolites indicated increased uptake of the drug
both in sheep and goats at divided dose schedules compared to single dose
administration (P < 0.05). The increased bioavailability of benzimidazole
anthelmintics in divided dose schedules could improve their efficacy and help in
extending their lives.
PMID- 9638079
TI - Gross anatomy of the accessory nerve and vagus nerve of the head and cranial neck
region in the Bactrian camel.
AB - Seven heads and necks of Bactrian camels were dissected to investigate the
origin, course, branches and distribution of the accessory nerve and vagus nerve
in the cranial cervical region. The spinal root and external branch of the
accessory nerve were not present, but there was a delicate communicating branch
between the dorsal root of the first cervical nerve and the root of the vagus
nerve. The sternocephalic muscle was innervated by the second cervical nerve
while the brachiocephalic and trapezius muscles were supplied by the sixth and
seventh cervical nerves. In the head and cranial cervical region of the Bactrian
camel the vagus nerve gave off the auricular branch, pharyngeal branch, cranial
laryngeal nerve, a common trunk to the larynx, oesophagus and trachea, and some
communicating branches connecting with the glossopharyngeal, hypoglossal, first
cervical nerves and the cranial cervical ganglion.
PMID- 9638080
TI - Ultrasonographic examination of 12 ovine vaginal prolapses.
PMID- 9638081
TI - Managed care and unintended pregnancy.
PMID- 9638082
TI - Adolescent pregnancy prevention in managed care.
PMID- 9638084
TI - Prevention of sexually transmitted diseases in an era of managed care: the
relevance for women.
PMID- 9638086
TI - Correlates and perceived outcomes of four types of employee development activity.
AB - Participation in 4 different types of development activity was studied in a
sample of manufacturing employees (N = 1,798). It was found that similar sets of
variables were linked to greater participation in 3 activities: required training
courses in work time, work-based development activity in work time, and career
planning activity in work time or an individual's own time. Three kinds of
reported benefits were studied, and the occurrence of these benefits was found to
vary between different types of development activity. Overall job satisfaction
and organizational commitment were significantly associated with prior
participation in required training courses and work-based development activity.
However, voluntary learning in one's own time was completely unrelated to these
work attitudes.
PMID- 9638087
TI - Psychosocial factors predicting employee sickness absence during economic
decline.
AB - Psychosocial factors such as work characteristics, life events, social support,
and personality were examined as predictors of the change in medically certified
sickness absence observed during a period of severe economic decline.
Longitudinal data, derived from self-reports and register-based information
relating to 763 local government employees, were collected at 3 points during a 5
year period: before the economic decline, during the nadir of that decline, and
immediately after the nadir. After the effects of prior absence and demographic
and lifestyle variables had been partialed out, the results of multiple Poisson
regression analyses showed that work characteristics play a major role in
forthcoming sickness absences. Negative life events and the personality trait
sense of coherence (in women) also predicted forthcoming absence rate. Social
support did not relate to absences either in men or in women.
PMID- 9638088
TI - Gender differences in ethical perceptions of business practices: a social role
theory perspective.
AB - This study presents a meta-analysis of research on gender differences in
perceptions of ethical decision making. Data from more than 20,000 respondents in
66 samples show that women are more likely than men to perceive specific
hypothetical business practices as unethical. As suggested by social role theory
(A. H. Eagly, 1987), the gender difference observed in precareer (student)
samples declines as the work experience of samples increases. Social role theory
also accounts for greater gender differences in nonmonetary issues than in
monetary issues. T. M. Jones's (1991) issue-contingent model of moral intensity
helps explain why gender differences vary across types of behavior. Contrary to
expectations, differences are not influenced by the sex of the actor or the
target of the behavior and do not depend on whether the behavior involves
personal relationships or action vs. inaction.
PMID- 9638089
TI - Self-efficacy as a mediator of the relationship between perceived union barriers
and women's participation in union activities.
AB - This study investigated the influence of union self-efficacy (expectations of
success in pursuit of union activities) as a mediator of the relationship between
perceptions of barriers to union participation and women's participation in union
activities (N = 89). Perceived barriers were defined in 4 domains (community,
family, union, work), and self-efficacy was operationalized based on C. Lee and
P. Bobko's (1994) analysis of self-efficacy measures (self-efficacy magnitude,
self-efficacy strength). Union self-efficacy was found to mediate the
relationship between the magnitude of perceived union barriers and the magnitude
of union participation, although mediation was limited to women with weak union
self-efficacy. Implications for designing training and intervention programs to
enhance women's participation in the face of perceived barriers are discussed.
PMID- 9638090
TI - The way we were: gender and the termination of mentoring relationships.
AB - The relationship between gender and the termination of mentoring relationships
was assessed in a matched sample of 142 male and female ex-proteges. Counter to
prevailing assumptions, when gender differences in rank, salary, tenure, and
other demographic and organizational variables were controlled, women did not
differ from men in the number or duration of prior relationships or in their
reasons for terminating the relationship.
PMID- 9638091
TI - Theory and configurality in clinical judgments of expert and novice
psychologists.
AB - This article shows that in judging the degree of pathology of mental patients,
expert psychologists, more than novices, assign heavier weight to the more
pathological information. This difference is explained in terms of the
professional socialization process of clinical psychologists.
PMID- 9638092
TI - [Lumbar bone density. Risk factor for vertebral fractures in women].
AB - BACKGROUND AND OBJECTIVE: The direct connections between a reduction in bone
density and an increase in the incidence of fractures with increasing age is well
known. When interpreting bone density measurements the attending physician is
confronted with an overlap of false-positive and false-negative parameters, as is
also the case with biochemical data. Aim of this study was to determine, in
addition to bone density, a fracture threshold, i.e. a value for bone density
with maximal sensitivity and specificity, in a representative cohort of women.
PATIENTS AND METHODS: 534 healthy women (mean age 60.9 +/- 8.07, range 40-83
years), seen in an out-patient osteological clinic between 1993 and 1996 were
included. After full biochemical investigation to exclude a metabolic bone
disease, bone density (LBD) of the lumbar vertebrae 1-5 and the number of
vertebral body fractures were documented, together with age and menopausal
status. LBD was measured by quantitative computed tomography (qCT), results being
analysed with the Wilcoxon 2-sample test and logistic regression and assessed by
receiver operating characteristics (ROC) analysis. RESULTS: None of the women
with a qCT value over 111 mg/cc had evidence of vertebral fractures. Those with
values under 60 mg/cc had at least one vertebral fracture (defined as at least
15% reduction in vertebral body height). There was a highly significant negative
correlation between age and LBD (r = -0.56; P < 0.0001), as well as between LBD
and the number of fractured vertebrae (r = -0.58, P < 0.0001). But there was no
longer any correlation between age and number of vertebral body fractures once
allowance was made for LBD (r = 0.001, not significant). The least overlap of
false-positive and false-negative values was at an LBD with qCT values of 102
mg/cc. CONCLUSIONS: LBD is the determining variable for fracture risk independent
of age. Despite an overlap of false-positive and false-negative LBD values, the
probability of fractures can be predicted from bone mineral content.
PMID- 9638093
TI - [Acute posterior wall infarct after factor VIII concentrate administration to a
patient with severe hemophilia A].
AB - HISTORY AND CLINICAL FINDING: A 69-year-old man with severe haemophilia A
sustained an acute myocardial infarction (MI) after self-administration of 3000
units factor VIII over 10 min. On admission he had no signs of heart failure.
INVESTIGATIONS: The ECG showed an acute posterior wall MI. Creatinekinase rose to
a maximum of 321 U/l with a significant MB proportion. The echocardiogram
demonstrated hypokinesia of the posterior wall. TREATMENT AND COURSE: After
initial thrombolysis treatment with a total of 100 mg rtPA according to an
accelerated scheme coronary angiography, performed because the symptoms
persisted, revealed two-vessel disease. A subtotal stenosis of the right coronary
artery was balloon-dilated with good primary results. Regular factor VIII
substitution was temporarily administered with the aim of initially achieving
high normal levels of factor VIII activity. CONCLUSION: Factor VIII substitution
in haemophilia A may promote thrombotic complications. Thrombolytic treatment and
balloon angioplasty of acute MI can be successfully performed even in patients
with severe haemophilia A.
PMID- 9638094
TI - [Sicca symptoms and hearing loss in Behcet's syndrome].
AB - HISTORY AND ADMISSION FINDINGS: A 39-year-old woman sustained an irreversible
hearing loss in the left ear, followed 6 months later by a left facial paresis.
Oral aphthous ulcers frequently recurred with fever of up to 39.5 degrees C. Her
general condition was noticeably poor. INVESTIGATIONS: An inflammatory disease
was suggested by an increased erythrocyte sedimentation rate (70/100 mm),
leucocytosis (18,500/microliter), decreased haemoglobin (10.2 g/l) and leftward
shift of the neutrophil granulocytes. Diagnostic tests for an infectious,
autoimmune or haemato-oncological disease were negative. TREATMENT AND COURSE:
Antibiotic and antimycotic treatment failed to bring lasting improvement.
Thrombophlebitis and venous thrombosis developed in both upper limbs and acute
episcleritis (scleritis) in the left eye. Behcet's disease with oral, ocular,
neurological, cutaneous and vascular involvement was diagnosed and treated with
chlorambucil (variable dosage around 7 mg/d orally), with rapid regression of
symptoms. 3 months later joint pains set in, and another 18 months later she
developed sicca symptoms (xerostomia with dry eyes): both responded to
symptomatic treatment. CONCLUSION: The combination of loss of hearing, sicca
syndrome and Behcet's syndrome has not been previously reported.
PMID- 9638095
TI - [Extragastric side effects of non-steroidal antirheumatic agents ].
PMID- 9638096
TI - [Adjuvant treatment for colon carcinoma. Results and perspectives].
PMID- 9638097
TI - [Antihypertensive therapy using a combination of angiotensin 1 receptor
inhibitors with angiotensin-converting enzyme inhibitors].
PMID- 9638098
TI - [Diagnosis and therapy of primary stomach lymphoma].
PMID- 9638099
TI - ["Bull-neck" in HIV-positive patients: result of therapy?].
PMID- 9638100
TI - [Ambulatory therapy concepts for a "forgotten disease:" tuberculosis].
PMID- 9638101
TI - Management of the third stage of labor.
PMID- 9638102
TI - Risk of stroke in patients with carotid bruits.
PMID- 9638103
TI - Calcium channel blockers and cardiovascular complications in hypertensive
diabetics.
PMID- 9638104
TI - Finasteride for BPH.
PMID- 9638105
TI - Potentiation of warfarin by acetaminophen.
PMID- 9638106
TI - Warming bupivacaine for intradermal anesthesia.
PMID- 9638107
TI - Lack of efficacy of cisapride and nizatidine in dyspepsia.
PMID- 9638108
TI - Identifying cardiac risk in patients with atypical chest pain.
PMID- 9638109
TI - Smoking cessation and weight gain.
AB - Cigarette smokers have a lower average body weight than nonsmokers, and the
cessation of smoking is associated with weight gain. Although this weight gain
does not offset the health benefits of smoking cessation, it is frequently a
source of concern for smokers planning to quit. The objective of our review was
to estimate the risk and duration of weight gain after cessation of smoking to
help physicians in counseling concerned smokers. We reviewed the literature by
doing a MEDLINE search using key words for articles on the changes in body weight
after smoking cessation. The retrieved data indicated that (1) the risk of weight
gain is highest during the 2 years immediately following smoking cessation, and
declines thereafter; (2) on average, sustained quitters gain about 5 to 6 kg in
weight; (3) physical exercise, older age, higher baseline body mass index, and
lower rates of smoking attenuate the degree of weight gained after smoking
cessation; and (4) the evidence regarding the permanence of the expected weight
gain is conflicting.
PMID- 9638110
TI - The rising tide of hospitalism: evidence-based or anecdote-based medicine?
PMID- 9638112
TI - The Spiritual Involvement and Beliefs Scale. Development and testing of a new
instrument.
AB - BACKGROUND: Spirituality is receiving greater attention in the medical
literature, especially in the family practice journals. A widely applicable
instrument to assess spirituality has been lacking, however, and this has
hampered research on the relationship between spirituality and health in the
clinical setting. METHODS: A new instrument, called the Spiritual Involvement and
Beliefs Scale, was designed to be widely applicable across religious traditions,
to assess actions as well as beliefs to address key components not assessed in
other available measures, and to be easily administered and scored. The
instrument is a questionnaire containing 26 items in a modified Likert-type
format. Following careful pretesting, the instrument was administered to 50
family practice patients and 33 family practice educators. The validity and
reliability of the instrument were then evaluated. RESULTS: By several measures,
instrument reliability and validity are very good, with high internal consistency
(Cronbach's alpha = .92); strong test-retest reliability (r = .92); a clear four
factor structure; and a high correlation (r = .80) with another established
measure of spirituality, the Spiritual Well-Being Scale. CONCLUSIONS: The
Spiritual Involvement and Beliefs Scale (SIBS) appears to have good reliability
and validity. Compared with other instruments that assess spirituality, the SIBS
has several theoretical advantages, including broader scope, use of terms that
avoid cultural-religious bias, and assessment of both beliefs and actions. More
testing is underway to further assess its usefulness.
PMID- 9638111
TI - Treatment of acute bronchitis in adults. A national survey of family physicians.
AB - BACKGROUND: The purpose of this study was to determine how family physicians in
the United States treat acute bronchitis in an otherwise healthy adult. METHODS:
A 33-item questionnaire on the diagnosis and treatment of acute bronchitis was
mailed to a random sample of 500 physicians who are members of the American Board
of Family Practice. RESULTS: Thirty-two of the 500 sampled physicians could not
be located by mail; 265 of those who received the questionnaire responded. The
response rate was 57% (265/468). Sixty-three percent of responding physicians
indicated that antibiotics are their first choice of treatment for the otherwise
healthy, nonsmoking adult with acute bronchitis. The decision to use antibiotics
as the first choice of treatment did not vary by physician's sex, age, years in
practice, practice location, practice type, or percentage of HMO patients. Only
6% of responding physicians reported using beta 2 agonist bronchodilators as
their first choice of treatment. Physicians in this study stated that they
prescribe an antibiotic 75% of the time in treating nonsmoking patients with
acute bronchitis (first choice or otherwise). If the patient is a smoker,
physicians reported that they prescribe antibiotics 90% of the time (F = 110.25;
df = 1; P > .0001). Physicians reported that for patients who smoke it takes
longer for coughs to totally resolve and longer for them to return to a normal
activity level than for nonsmokers. CONCLUSIONS: Family physicians report that
antibiotics are their most common treatment for acute bronchitis in the otherwise
healthy adult. Previous clinical trials have shown only marginal improvement in
symptoms when patients with this condition are treated with an antibiotic. With
antibiotic resistance emerging as a major global health problem, it is essential
that other methods of treatment be evaluated.
PMID- 9638113
TI - Criteria used by clinicians to differentiate sinusitis from viral upper
respiratory tract infection.
AB - BACKGROUND: Acute sinusitis and upper respiratory tract infections (URIs) share
many common symptoms and signs. Objective criteria have been identified that are
valid for distinguishing between these two clinical problems. The objective of
this study was to determine how often clinicians use these validated criteria and
how often they rely on clinical cues that are less valuable for differentiating
sinusitis from URI. METHODS: We performed a retrospective review of 734 patients
with a diagnosis of acute sinusitis (n = 367) or URI (n = 367) at a family
practice residency training site over a 3-year period. Charts were reviewed to
ascertain patient demographics, past history, current symptoms, physical
findings, and treatment prescribed. RESULTS: Patients with sinusitis were likely
to be older, female, smokers, have a history of allergic rhinitis, and have
longer symptom durations. Complaints of sinus pressure or discolored nasal
discharge and the finding of sinus tenderness were strongly associated with the
diagnosis of sinusitis. In multivariate analysis, eight factors were
independently associated with the diagnosis of sinusitis. Four clinical cues
alone (sinus tenderness, sinus pressure, postnasal drainage, and discolored nasal
discharge) were highly associated with the diagnosis of sinusitis and explained
60% of the variation in the diagnosis between sinusitis and URI. CONCLUSIONS:
Physicians tend to rely on four factors to differentiate sinusitis from URIs.
Only one of these has been shown to be a reliable predictor of acute sinusitis.
This use of unreliable criteria may lead to misdiagnoses and inappropriate
prescriptions for antibiotics.
PMID- 9638114
TI - Screening men for partner violence in a primary care setting. A new strategy for
detecting domestic violence.
AB - BACKGROUND: Health care domestic violence initiatives have given little attention
to screening men for violent behavior toward their partners. We conducted this
study to assess whether men would answer questions about partner violence in a
health care setting, to estimate the prevalence of violent behavior in male
primary care patients, and to identify characteristics associated with violent
behavior. METHODS: We used an anonymous written survey at three family medicine
clinics. The survey instrument included the Conflict Tactics Scale to measure
aggressive and violent behavior. Standard questions assessed demographic
variables and health behaviors. RESULTS: Three hundred seventy-five men were seen
during the study. Of these, 317 (85%) participated and 237 met inclusion
criteria. Thirty-two men (13.5%, 95% confidence interval (CI), 9.1-17.9)
disclosed physical violence toward their partner in the previous 12 months. Ten
men (4.2%, 95% CI, 3.7-4.8) reported severe violence. Men with increased alcohol
consumption, depression, or history of abuse as children were more likely to
report violent behavior. Presence of all three variables resulted in a
probability of violence of 41%, compared with a baseline probability of 7% if no
risk factors were present. CONCLUSIONS: Primary care physicians should consider
screening male patients for aggressive behavior toward their intimate partners.
Physicians should be especially cognizant of this possibility in men who are
depressed, heavy alcohol users, or were childhood victims of abuse.
PMID- 9638115
TI - Physician employment status and practice patterns.
AB - BACKGROUND: Many physicians today are employed by another physician, group,
hospital, HMO, or other organization. However, the differences in the
characteristics, practice patterns, and patient outcomes of self-employed and
employed physicians are not well understood. METHODS: The practices of 108
community family physicians in northeast Ohio were assessed using a multimethod
cross-sectional design. Physician characteristics were assessed by questionnaire.
Direct observation of 3536 consecutive patient visits was used to measure time
use and the delivery of preventive services recommended by the US Preventive
Services Task Force. Patient satisfaction was assessed with the Medical Outcomes
Study (MOS) 9-item Visit Rating Form. RESULTS: Employed physicians were more
likely to be female, in group practice, work fewer hours, and see fewer patients.
Job satisfaction was similar between the two groups, but employed physicians
reported greater satisfaction with leisure and family time. Employed physicians
spent more time per patient visit, scheduled a larger percentage of well-care
visits, and were more likely to refer to specialists. Employed physicians also
spent a greater proportion of their patients' visit time performing history
taking and eliciting family information, and a lesser proportion of time on
physical examination, planning treatment, providing health education, and
chatting. Recommended screening and health habits counseling preventive services
were more likely to be delivered by employed physicians. Patient satisfaction was
similar for the two groups. CONCLUSIONS: Primary care physician characteristics
and practice patterns differ by employment status. The consequences of the trend
toward a largely employed physician workforce as reported in this study should be
carefully considered.
PMID- 9638116
TI - Chronic appendicitis: does it exist?
AB - The typical presentation of acute appendicitis is well known. A few patients,
however, have had an atypical clinical course suggestive of recurrent appendiceal
inflammation, which has been confirmed by appendectomy. Therefore, in the
evaluation of a patient with abdominal pain, a history of similar episodes should
not preclude a diagnosis of appendicitis.
PMID- 9638117
TI - Misoprostol in obstetrics and gynaecology--unregistered, dangerous and essential.
PMID- 9638118
TI - Heart scanner--who's between a rock and a hard place?
PMID- 9638119
TI - Solid science and hard logic--the rock on which good treatment is based.
PMID- 9638121
TI - Hypertension care at a Cape Town community health centre.
AB - OBJECTIVES: To describe the demographic profile of hypertensive patients and the
quality of care for hypertension at a Cape Town community health centre (CHC).
DESIGN: Prospective, descriptive study. SETTING AND SUBJECTS: Medium-sized CHC,
attended by 1,098 hypertensive patients during a 1-year period from 1 January
1992. OUTCOME MEASURES: Default rate--proportion of due visits not attended. Loss
to follow-up--proportion of patients persistently defaulting or not responding to
recall. Frequency of blood pressure measurement--per 12 due visits. Compliance-
proportion of patients collecting > or = 75% of antihypertensive drugs. Blood
pressure control--mean blood pressure of aggregated readings; and proportion
controlled (< 160/95 mmHg) on the basis of all blood pressure readings and mean
blood pressures of individual patients with two or more readings during the study
period. RESULTS: More than half (51.6%) of the hypertensive patients were aged >
or = 65 years; 81.7% were female. The default rate was between 11.9% and 19.4%.
Compliance was high (76.9%). Loss to follow-up was 8.1%. Blood pressure was
recorded a mean of 4.0 times per 12 due visits. There were no significant gender
differences with regard to these measures. Mean blood pressure was 158.3/89.6
mmHg. Over half (56.7%) of all individual readings over the year were
uncontrolled and 51.4% of patients were found to be uncontrolled when categorised
by their mean blood pressure. Control was significantly poorer among women > or =
65 years. CONCLUSION: We found better compliance, more frequent blood pressure
measurement, and lower defaulting and loss to follow-up compared with previous
South African studies in similar settings. Despite this, blood pressure control
was mediocre. Possible explanations for this are discussed. The low proportion of
male hypertensives attending the CHC suggests that the accessibility or
acceptability of care is poor for this group. The study illustrates the potential
for research in this setting and for the use of computers to monitor the quality
of primary care.
PMID- 9638122
TI - Improving cost-effectiveness of hypertension management at a community health
centre.
AB - OBJECTIVES: To describe the pattern of prescribing for hypertension at a
community health centre (CHC) and to evaluate the impact of introducing treatment
guidelines and restricting availability of less cost-effective antihypertensive
drugs on prescribing patterns, costs of drug treatment and blood pressure (BP)
control. DESIGN: Before/after intervention study. SETTING: Medium-sized CHC in
the Cape Flats area of Cape Town. SUBJECTS: 1,084 hypertensive patients attending
the CHC, who had at least two prescriptions for antihypertensive drugs during a 1
year period starting on 1 January 1992. INTERVENTIONS: 1. Implementation of
stepped-care guidelines for hypertension, specifying treatment with more cost
effective drugs and minimising drug treatment. 2. Reducing availability for
routine prescribing by CHC doctors of 10 less cost-effective antihypertensive
drugs or drug combinations. OUTCOME MEASURES: 1. Mean number of drugs prescribed
per patient. 2. Proportion of prescriptions for: each major class of
antihypertensive drug; restricted availability and freely prescribable drugs; and
more and less cost-effective drugs. 3. Mean monthly cost of drugs prescribed per
patient. 4. Mean blood pressure and proportion of BP readings controlled (<
160/95 mmHg) or uncontrolled (> or = 160/95 mmHg). RESULTS: A mean of 1.7 active
drugs was prescribed per patient per visit. The most frequently prescribed drugs
were thiazide-like diuretics (44.8%), centrally acting agents (28.4%) and b
blockers (13.2%). Mean monthly drug costs per patient decreased significantly by
R1.99 (24.2%) from R8.24 to R6.25 between the first and last prescription for
each patient (exclusive of any reduction due to withdrawal of treatment). This
was attributable to reduced prescribing of more expensive drugs withdrawn from
routine use and a 51.1% increase in prescribing of the most cost-effective drugs.
The overall annual cost-saving of the changes in prescribing for this CHC are
estimated at R75 150. Blood pressure control did not change significantly.
CONCLUSION: The pattern of changes in prescribing and drug costs was consistent
with a causal effect of the interventions. The study demonstrates the potential
for improving cost-effectiveness of hypertension care in primary care in South
Africa and the potential for research in this setting.
PMID- 9638123
TI - Survival of children in Cape Town known to be vertically infected with HIV-1.
AB - OBJECTIVE: To determine the survival patterns of children in Cape Town known to
be vertically infected with HIV. DESIGN: Retrospective record review of children
diagnosed with symptomatic HIV infection during the period 1 December 1990-31 May
1995. SETTING: Hospitals in the Cape Town metropolitan area. PATIENTS: 193
children were known to be vertically HIV-infected. HIV diagnosis was based on the
following criteria: two positive HIV enzyme-linked immunosorbent assays (ELISAs)
in children older than 15 months and a positive ELISA together with a positive
polymerase chain reaction (PCR) in younger children. The mothers of the children
were known to be HIV-positive. On the basis of the presenting clinical findings
children were assigned to a disease severity category (A, B or C) according to
the Centers for Disease Control and Prevention (CDC)'s 1994 revised
classification system for HIV infection in children. OUTCOME MEASURES: Survival
was analysed according to the Kaplan-Meier method. Survival time was defined as
the length of time between clinical diagnosis of HIV and death or last contact
with the health services. Mortality risk in relation to specific variables at
diagnosis such as age and clinical manifestations was determined by calculation
of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The median age
at diagnosis was 5 months; 72% of children were aged less than 1 year at
diagnosis. According to the CDC clinical classification, 47 (24%) fell into
category A, 111 (58%) into category B and 35 (18%) into category C. Of the 193
patients 85 (44%) were alive at the time of review, 65 (34%) had died and 43
(22%) were lost to follow-up. Risk of death was significantly associated with age
less than 6 months (OR 4.7, CI 2.1-10.3) and severe disease, i.e. CDC category C
(OR 2.7; CI 1.1-6.9) at time of diagnosis. The median survival for all the
children from time of diagnosis was 32 months. Infants diagnosed before 6 months
of age had significantly shorter median survival (10 months) compared with 36
months for those diagnosed at 7-12 months of age. For the children over the age
of 12 months the cumulative proportion surviving at 48 months was 78%. Children
with severe disease (category C) had a median survival of 21 months,
significantly lower than that in category B (32 months). For the children in
category A the cumulative proportion surviving at 48 months was 66%. CONCLUSION:
The median survival of children with HIV was 32 months from time of diagnosis,
and survival was influenced by age and disease severity.
PMID- 9638124
TI - Electron beam computed tomography for the diagnosis of cardiac disease.
AB - Electron beam computed tomography (EBCT) of the heart is a new modality which
will alter the way cardiology is practised. It allows for the detection of early
coronary artery disease (CAD) in asymptomatic individuals, regardless of their
level of risk as assessed by traditional risk factor analysis. Compared with risk
analysis based on risk factors alone, an assessment which also utilises
quantitative measurements of coronary artery plaque by EBCT allows for more
precise determination of the need for medical therapy. Non-invasive intravenous
contrast EBCT coronary angiography can identify significant obstructive CAD, and
should reduce the need for conventional coronary angiography. Incorporation of
EBCT into routine medical practice is more cost-effective than other modalities
currently available. This paper reviews relevant original articles on EBCT and
preventive cardiology published in peer-reviewed medical journals, and assesses
the implications of EBCT for preventive cardiology.
PMID- 9638125
TI - Enterococcal endocarditis--a case treated with teicoplanin and amoxycillin.
AB - The study aimed to determine the antibacterial therapy effective in the cure of
endocarditis caused by Enterococcus faecalis resistant to clinically achievable
levels of vancomycin. Isolation of the causative enterococcus had been achieved
by direct inoculation of the resected valve into the culture medium in theatre.
The patient was known to have had an aortic valve defect since childhood and had
recently undergone splenectomy following trauma. Blood cultures were negative
prior to valve replacement. A perivalvular abscess was noted at operation. In
vitro minimal bactericidal results and serum activity were the basis of the
postoperative choice of drugs. The minimal bactericidal level of teicoplanin was
250 micrograms/ml and that of amoxycillin 64 micrograms/ml. Neither is achievable
with the advocated dosage. A combination of these two cell-wall-active agents
successfully eliminated the infection. Acting at two different sites in the
synthesis of the bacterial cell wall, teicoplanin and amoxycillin were found to
be bactericidal in vitro at the trough levels of the antibiotics in the serum.
The patient recovered fully.
PMID- 9638126
TI - Limb reduction anomaly after failed misoprostol abortion.
PMID- 9638127
TI - A peripheral hospital can be fulfilling--for staff and patients alike.
PMID- 9638128
TI - The ethics of physician-assisted suicide and euthanasia.
PMID- 9638129
TI - Heart scanner 'min dae'?
PMID- 9638131
TI - Training of rural doctors--a means of enhancing the effectiveness of referrals.
PMID- 9638133
TI - Therapeutic application of organ electrodermal diagnostics for pain.
PMID- 9638134
TI - Caring for babies who survive an abortion attempt--an ethical dilemma.
PMID- 9638135
TI - Late terminations of pregnancy.
PMID- 9638137
TI - Complete nucleotide sequence of wheat yellow mosaic bymovirus genomic RNAs.
AB - The complete sequences of wheat yellow mosaic bymovirus (WYMV) RNA1 and RNA2 were
determined. RNA1 is 7636 nucleotides long [excluding the 3'-poly(A)], and codes
for a 269 kDa polyprotein of 2,404 amino acids which contains the capsid protein
(CP) at the C terminus and seven putative nonstructural proteins. RNA2 is 3,659
nucleotides long and codes for a polyprotein of 904 amino acids which contains a
28 kDa putative proteinase and a 73 kDa polypeptide. These functional proteins
are arranged as in RNA1 and RNA2 of barley yellow mosaic bymovirus (BaYMV).
Comparisons with the sequence reported for the 3' half of RNA1 of wheat spindle
streak mosaic bymovirus (WSSMV) from Southern France show that WYMV and WSSMV
have a similar genetic organization. However, WYMV and WSSMV share only 77% amino
acid sequence identity in their deduced CPs in spite of their close serological
relationship, and 74% nucleotide sequence identity in their 3' non-coding
regions. Thus, the sequence data indicate that WYMV and WSSMV are not strains of
the same virus, which has long been suggested, but are distinct virus species
within the genus Bymovirus of the family Potyviridae.
PMID- 9638138
TI - Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL.
AB - We assessed the genetic polymorphism of mannose-binding lectin (MBL) in 93
patients with chronic hepatitis C (45 responders and 48 nonresponders to
interferon) and 218 healthy controls. Mutant allele was identified only at codon
54 (Gly-->Asp), leading to three genotypes (54 m/m, 54 W/m, and 54 W/W).
Frequency of 54 m/m was significantly lower in interferon-responders (2.2%),
compared to those in nonresponders (14.6%) and controls (10.6%): p < 0.05. Our
results suggest that homozygous carriage of the variant allele of codon 54 of MBL
may predict poor response to interferon in chronic hepatitis C patients.
PMID- 9638139
TI - Two avian H10 influenza A virus strains with different pathogenicity for mink
(Mustela vison).
AB - We compared two strains of avian influenza A viruses of subtype H10 by exposing
mink to aerosols of A/mink/Sweden/3,900/84 (H10N4) naturally pathogenic for mink,
or A/chicken/Germany/N/49, (H10N7). Lesions in the respiratory tract during the
first week after infection were studied and described. Both virus strains caused
inflammatory reactions in the lungs and antibody production in exposed mink but
only mink/84 virus was reisolated. The lesions caused by mink/84 virus were more
severe with higher area density of pneumonia, lower daily weight gain, and more
virus in the tissues detected by immunohistochemistry. The results indicate that
mink/84 (H10N4), but not chicken/49 virus (H10N7), established multiple cycle
replication in infected cells in the mink.
PMID- 9638140
TI - Experimental induction of mucosal disease: consequences of superinfection of
persistently infected cattle with different strains of cytopathogenic bovine
viral diarrhea virus.
AB - Mucosal disease (MD) can be induced in cattle persistently infected with
noncytopathogenic bovine viral diarrhea virus (ncp BVD virus) by superinfecting
them with antigenically related cytopathogenic (cp) BVD virus strains. While some
of these animals succumb to early onset MD after 2 to 3 weeks post infectionem
(p.i.), others only react by producing neutralizing antibodies against the cp BVD
virus strain and may develop late onset MD after longer incubation periods. The
aim of this study was to determine if an increasing degree of antigenic homology
between the ncp and the superinfecting cp BVD virus strains as determined by
their comparative reactivity with E2 glycoprotein specific monoclonal antibodies
(mabs) increases the probability of inducing early or late onset MD,
respectively. For this, each two of eight clinically healthy animals from the
same herd and persistently infected with the same ncp BVD viruses were
superinfected with four different cp BVD virus strains. As only two of these
animals developed late onset MD, one animal from a different herd that developed
early onset MD was included in the study. Besides clinical observation and
testing for antibody production, virus isolation and characterization of the cp
BVD virus isolates were performed. The results indicate that antigenic similarity
as determined by comparative mab analysis alone is not sufficient to allow
prediction of the outcome of the disease.
PMID- 9638141
TI - Defective RNA packaging is responsible for low transduction efficiency of CAEV
based vectors.
AB - Replication defective retroviral vectors are regularly used for transfer and
expression of exogenous genes into dividing cells and in animals. Since
lentiviruses are able to infect terminally differentiated and non-dividing cells,
their use to produce replication defective vectors may overcome this limitation.
We developed two replication-defective lentiviral vectors based on the genome of
Caprine Arthritis Encephalitis Virus (CAEV). The first vector (pBNL2) carries the
neo and lacZ marker genes. Neo gene is expressed from a genomic RNA and lacZ gene
from a subgenomic RNA. The second vector (pCSHL) carries a single fusion gene
encoding both phleomycin resistance and beta-galactosidase activity. Replication
competent CAEV was used as helper virus to provide the viral proteins for
transcomplementation of these vectors. Our data demonstrated that the genomes of
both vectors were packaged into CAEV virions and transduced into goat synovial
membrane cells following infection. However, the vector titers remained 3 to 4
logs lower than those of CAEV. Further analysis showed a lack of accumulation of
unspliced pBNL2 RNA into the cytoplasm of producer cells resulting in the
packaging of pBNL2 sub-genomic RNA only. In contrast, RNA produced from pCSHL
vector was correctly transported to the cytoplasm and more efficiently packaged
than the pBNL2 sub-genomic RNA as revealed by slot-blot and quantitative RT/PCR
analyses. However this higher packaging efficiency of pCSHL genome did not result
in a higher transduction efficiency of lacZ gene.
PMID- 9638142
TI - Genetically determined resistance to flavivirus infection in wild Mus musculus
domesticus and other taxonomic groups in the genus Mus.
AB - Inherited resistance to flaviviruses in laboratory mice is a rare trait conferred
by an autosomal dominant gene (Flvr). To provide information on genetic
resistance to flaviviruses in wild mice, we analysed (i) wild M. m. domesticus
trapped in Australia, and (ii) mice representing other species and subspecies in
the genus Mus. Mice were screened for resistance relative to C3H/HeJ mice by
intracerebral challenge with Murray Valley encephalitis virus or yellow fever
virus, and breeding studies were undertaken to identify inherited resistance
factors. Widespread flavivirus resistance was demonstrated in Australian M. m.
domesticus. A single, autosomal dominant Flvr-like gene appeared to be primarily
responsible, but there was some evidence for additional inherited resistance
factors. Flavivirus resistance was also identified in other taxonomic groups, and
a genetic basis for this resistance was demonstrated in M. m. musculus (Skive),
M. spretus, and M. spicilegus. Interestingly, M. m. musculus (CZI-O) were more
susceptible than C3H/HeJ mice. Our findings show that genetic resistance to
flaviviruses is common in divergent taxonomic groups in the genus Mus, suggesting
that the trait has an ancient evolutionary origin, but whether flavivirus
resistance genes have an anti-viral role or serve some other function is unknown.
PMID- 9638143
TI - Fas antigen expression and apoptosis of lymphocytes in macaques infected with
simian immunodeficiency virus strain mac.
AB - To investigate the role of apoptosis in the pathogenesis of HIV infection we used
macaques infected with simian immunodeficiency virus (SIV) as a primate model and
examined the characteristics of the apoptosis of lymphocytes in SIV mac-infected
macaques. In vitro apoptosis was more strongly induced in peripheral blood
mononuclear cells (PBMC) from SIV mac239-infected macaques than those from
uninfected controls. We found that the frequency of Fas antigen-positive cells
was higher in PBMC from SIV mac-infected macaques than from uninfected controls,
and in vitro apoptosis of PBMC was suppressed by an inhibitor of the interleukin
1 beta converting enzyme (ICE) family proteases. In biopsied lymph nodes, the
number of apoptotic nuclei in T cell-dependent areas was higher in SIV mac
infected macaques than in uninfected controls. A higher number of apoptotic
nuclei in lymph nodes of SIV mac-infected macaques was observed in the stage of
persistent general lymphadenopathy than in those with AIDS-related complex, while
there was no significant difference in the extent of apoptosis of cultured PBMC
among the SIV mac-infected macaques. These results suggest that in vitro
apoptosis is mediated by the Fas/Fas ligand and ICE system and that apoptosis in
lymph nodes may be more closely related to the stage of SIV mac infection than is
that of cultured PBMC.
PMID- 9638144
TI - Genetic targets for the detection and identification of Venezuelan equine
encephalitis viruses.
AB - Rt-PCR probes targeted to different gene sequences of VEE (Venezuelan equine
encephalitis) virus strain TC-83 were assessed for their sensitivity, specificity
and non-specific cross-reactivity. A generic VEE virus amplimer
(VNSP4F2/VNSP4R2), targeted against nsP4 was identified, which was sensitive
(detected at least 10 pfu) and robust (worked over a wide range of salt
concentrations and annealing temperatures). An E2 amplimer designed against TC
83, (VE2F/VE2R), identified VEE strains TRD (1AB), P676 (1C), 3880 (1D)
Everglades (2) vRNA whilst a second E2 primer pair designed against strain
68U201, (68UF/68UR), identified all the remaining VEE viruses in the sero
complex. This would suggest that the VEE virus E2 gene can be sub-divided at the
genetic level into two separate groups making it a useful target for
differentiation of serosubtypes 1 and 2 from the other VEE virus subtypes. Using
a panel of amplimers targeted to different VEE genes and strains it was possible
to distinguish between most of the serotypes, but most importantly, we were able
to detect the epizootic strains TRD and P676 as well as other VEE viruses
implicated in human disease (sero-subtypes 1D and 1E).
PMID- 9638145
TI - Identification and characterization of the Spodoptera littoralis
nucleopolyhedrovirus type B lef-3 gene.
AB - We have identified a gene from the Spodoptera littoralis nucleopolyhedrovirus
type B (SpliNPV-B) with several characteristics that suggest that it is
homologous to the lef-3 genes of the Autographa californica and Orgyia
pseudotsugata NPVs (AcMNPV and OpMNPV, respectively). The SpliNPV-B lef-3 gene
was mapped between 43.6 and 45.5 map units of the SpliNPV-B genome. Northern blot
analysis showed that SpliNPV-B lef-3 was expressed as a 1.6 Kb transcript at 5 h
post infection (p.i.), reached high levels at 24 h p.i., and remained highly
expressed at 56 h p.i. Transcription of SpliNPV-B lef-3 initiated at two distinct
sites downstream from a TATA-box motif and terminated 25 nucleotides downstream
from the translation stop site of the putative LEF-3 polypeptide. The 5'
boundaries of lef-3 promoter elements were investigated by transient expression
assays, which revealed that the major components of the lef-3 promoter are within
a 183 base pair region upstream of the distal transcription initiation site.
Transfection of SpliNPV-B infected Sf9 cells with anti-sense oligonucleotides
designed to inhibit LEF-3 expression resulted in substantial reduction of viral
DNA replication, suggesting that the role of SpliNPV-B lef-3 may be similar to
that of AcMNPV and OpMNPV lef-3 genes, which are essential for viral DNA
replication.
PMID- 9638146
TI - Evidence that whitefly-transmitted cowpea mild mottle virus belongs to the genus
Carlavirus.
AB - Two strains of whitefly-transmitted cowpea mild mottle virus (CPMMV) causing
severe (CPMMV-S) and mild (CPMMV-M) disease symptoms in peanuts were collected
from two distinct agro-ecological zones in India. The host-range of these strains
was restricted to Leguminosae and Chenopodiaceae, and each could be distinguished
on the basis of symptoms incited in different hosts. The 3'-terminal 2500
nucleotide sequence of the genomic RNA of both the strains was 70% identical and
contains five open reading frames (ORFs). The first three (P25, P12 and P7)
overlap to form a triple gene block of proteins, P32 encodes the coat protein,
followed by P12 protein located at the 3' end of the genome. Genome organization
and pair-wise comparisons of amino acid sequences of proteins encoded by these
ORFs with corresponding proteins of known carlaviruses and potexviruses suggest
that CPMMV-S and CPMMV-M are closely related to viruses in the genus Carlavirus.
Based on the data, it is concluded that CPMMV is a distinct species in the genus
Carlavirus.
PMID- 9638147
TI - Characterisation of an avian influenza A virus isolated from a human--is an
intermediate host necessary for the emergence of pandemic influenza viruses?
AB - The partial sequencing of the internal and the neuraminidase genes of isolate
268/96 obtained from a woman with conjunctivitis showed all seven to have closest
homology with avian influenza viruses. The entire nucleotide sequence of the
haemagglutinin gene of 268/96 had close, 98.2%, homology with an H7N7 virus
isolated from turkeys in Ireland in 1995. This appears to be the first reported
case of isolation of an influenza A virus from a human being infected as a result
of direct natural transmission of an avian influenza virus from birds.
PMID- 9638148
TI - The roles of vif and ORF-A genes and AP-1 binding site in in vivo replication of
feline immunodeficiency virus.
AB - To examine the in vivo roles of auxiliary genes and regulatory elements of feline
immunodeficiency virus (FIV), the provirus load in various tissues of cats
infected with each of the mutant viruses (delta vif, delta ORF-A and delta AP-1)
was studied. Although all mutant viruses could infect various tissues, provirus
loads in various tissues especially those in cats infected with delta vif virus
were lower than those with the wild-type virus. Our results indicate the
significance of vif and ORF-A genes and AP-1 binding site of FIV for efficient
viral replication and full pathogenicity in cats.
PMID- 9638149
TI - Effects of GB virus-C/hepatitis G virus on hepatitis B and C viremia in multiple
hepatitis virus infections.
AB - We found that patients with dual HBV and GBV-C/HGV infection had comparable serum
HBV DNA positivity and mean virus concentration compared with age-matched HBV
carriers, and those with triple infection had a significantly lower HBV DNA
positivity. Serum HCV RNA positivity and mean virus titer were similar between
HCV carriers with or without GBV-C/HGV co-infection, and those with GBV-C/HGV co
infection seemed to have a lower serum ALT level. These data suggest that GBV
C/HGV infection exerts no significant suppression on levels of chronic hepatitis
B or hepatitis C viremia.
PMID- 9638150
TI - Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes
of non-neoplastic tonsils by in situ hybridization and in situ PCR.
AB - Non-neoplastic tonsils were analyzed for detection of Epstein-Barr virus (EBV)
positive cells by in situ hybridization and in situ PCR. EBV-encoded small
nuclear RNA 1(EBER1)-positive cells were found in 28.2% of the tonsils and were
evenly localized in the extrafollicular area and within germinal centers. Latent
membrane protein 1 (LMP1)-positive cells were also dispersed in the
extrafollicular and germinal center. Using in situ DNA-DNA hybridization, the EBV
positive signals were observed in the upper epithelial cell layers of the
tonsils. In addition, in situ PCR detected EBV DNA-positive cells in the lower
epithelial cell layers and lymphoid cells.
PMID- 9638151
TI - Nucleotide sequence of the gene encoding the RNA polymerase and the 3' non-coding
region of a bovine enterovirus Japanese isolate: rapid synonymous substitutions
between European and Japanese strains.
AB - The nucleotide sequences of the genome RNA encoding the RNA polymerase and the 3'
non-coding region (NCR) of bovine enterovirus (BEV) serotype I Japanese isolate,
MZ468, were determined. The genetic distance between the two BEV serotype I
strains, MZ468 and VG-5-27, was calculated by pairwise comparison of nucleotide
sequences. The synonymous substitution rate was high (1.40 x 10(-2)/site/year),
and of the same order as those of influenza virus HA, HIV-1 gag and env, and
enterovirus 70 VP1 genes.
PMID- 9638152
TI - Turnover of hepatitis C virus genotypes in hemodialysis patients.
AB - Hepatitis C virus (HCV) genotypes were determined in hemodialysis patients with a
high prevalence and incidence of infection. A change of HCV genotype was observed
in 6/14 follow-up samples analyzed 13 and 21 months later. The appearance and
disappearance of HCV genotypes may be due to either genotype-specific
intermittent viremic status or viral interference.
PMID- 9638153
TI - A proposal for a new (third) genus within the family Adenoviridae.
AB - This article presents a proposal for the establishment of a new adenovirus genus
to accommodate certain bovine, ovine, and avian adenoviruses with special
characteristics which differentiate them from members of the existing genera
Mastadenovirus and Aviadenovirus. This proposal has been developed from earlier
versions with advice from the Adenovirus Study Group of the International
Committee on Taxonomy of Viruses (ICTV).
PMID- 9638154
TI - [A truly useful law (shall we call it Cardinal Law?)].
PMID- 9638155
TI - [Villous-lipomatous proliferation of synovial membrane of the knee (lipoma
arborescens). Magnetic resonance findings].
AB - PURPOSE: We reviewed the imaging patterns of the villous-lipomatous proliferation
of the knee synovial membrane (lipoma arborescens), with special reference to the
role of MRI in the diagnosis of this rare condition. MATERIAL AND METHODS: 1994
to 1996, we examined four patients, none of them with a history of knee trauma.
The clinical picture was characterized by moderate and painful suprapatellar
swelling in three cases and by moderate suprapatellar swelling alone in one case.
All patients were examined with conventional radiography and MRI; two were
submitted to US and two to CT. The diagnosis of lipoma arborescens was suggested
on the basis of imaging patterns and then confirmed by histologic findings.
RESULTS: Conventional radiography showed a roughly oblong slim opacity in the
suprapatellar recess in all cases; the joint space was always preserved. US
showed a villous lesion surrounded by fluid, but provided no specific data on its
nature. CT and MRI not only provided better location and morphologic detailing
and showed the relationships with articular structures better, but also permitted
the direct identification of the fat nodules within the abnormal synovial
reaction. CONCLUSION: We stress the role of MRI in suggesting the correct
diagnosis of lipoma arborescens, as it was subsequently confirmed in our series
by histologic findings. In fact, fat-suppression sequences, after T1-weighted SE,
can typify fat tissue.
PMID- 9638156
TI - [Computerized tomography assessment of replacement of the cruciate ligaments of
the knee].
AB - January, 1993, to December, 1995, we examined with CT 44 patients submitted to
surgical replacement of knee cruciate ligaments, namely 18 anterior cruciate
ligaments (ACL) and 6 posterior cruciate ligaments (PCL). ACL was replaced with a
patellar tendon graft (Eriksson technique) in 23 cases and with a semitendinous
graft (Lindemann-Bousquet technique) in 7 cases. The autologous new ligament
appeared as a laminar structure of intermediate density. The tendon had been
covered with a synthetic lining (Leeds-Kejo) in 10 of the above cases, while the
new ACL graft was completely synthetic in 8 cases, which synthetic allografts
appeared hyperdense relative to autologous new ligaments. PCL replacement had
been performed with Augustine technique (patellar tendon graft in a tibial
tunnel) in 3 cases, with Hughston technique (medial gastrocnemius graft in a
medial condylar tunnel) in 2 cases and with a synthetic graft (Gore-tex) in 1
case. Twelve of 38 new ACLs were injured (7 Eriksson, 3 Lindemann-Bousquet and 2
synthetic grafts): the injured new ligament was enlarged and hypodense, or
involved in atrophic absorption. The new ligament was partially calcified in one
of the 3 patients with PCL replacement with a patellar tendon graft (Augustine
technique). The bone bract was dislocated in the intercondylar notch in a patient
submitted to Hughston surgery because of proximal disinsertion of the new
ligament. The Gore-tex new PCL was sinuous in the proximal tract, with intra
articular calcified loose bodies. CT adequately depicted surgical results and
diagnosed the new ligament injuries and other articular abnormalities. MRI is
currently the gold standard in the multiplanar studies of the postoperative knee,
but CT can be confidently used to identify ligament injuries and intra-articular
calcified loose bodies.
PMID- 9638157
TI - [Deglutition in patients treated with reconstructive laryngectomy].
AB - INTRODUCTION: We stress the importance of dynamic radiologic studies of
swallowing in the patients submitted to reconstructive laryngectomy. MATERIAL AND
METHODS: January, 1989, to December, 1996, we examined 36 patients submitted to
reconstructive laryngectomy, namely cricohyoidoepiglottopexy in 34 cases,
cricohyoidopexy in 1 case and Guerrier's cricohyoidoepiglottopexy in 1 case.
Dynamic radiologic studies were performed with fluoroscopic videorecording (Sony
U-Matic RM 580) from an X-ray unit. The study was performed with the patients
standing or sitting, initially acquiring AP and LL fluoroscopic images of the
oropharyngeal region at rest and during swallowing. The patients then swallowed 2
boluses of 5 ml liquid (60%) and semiliquid (250%) barium. When aspiration was
suspected, we began with a 2-ml bolus. RESULTS: The patients were grouped by
symptoms: group A patients had no symptoms, group B patients had dysphagia and
group C patients presented aspiration. The functional changes were: reduced
pharyngeal contraction, reduced epiglottis deflection, reduced hyoid bone
elevation, aspiration, altered upper esophageal sphincter function. The organic
alterations were: parapharyngeal diverticulum, pharyngeal stenosis, posterior
pharyngeal wall introflexion. Three group A patients had severe posterior
pharyngeal wall introflexion, 4 had marked retention and 2 of them presented
postswallowing aspiration. Two group B patients had major retention, 1
cricopharyngeal incoordination, 3 posterior pharyngeal wall introflexion, 2 a
pseudodiverticulum and 2 a luminal stenosis. Seven group C patients had
intraswallowing and 3 postswallowing aspiration. CONCLUSION: The
videofluorographic identification of organic and functional complications,
sometimes unknown in asymptomatic patients, is useful for therapy and suggests
the speech specialist the best compensatory mechanism to improve the patients'
swallowing and consequently their quality of life. Moreover, videofluorography of
swallowing is a very useful tool in the follow-up, to monitor treatment outcome
after rehabilitation.
PMID- 9638158
TI - [Is mammography useful in the detection of breast cancer in women 35 years of age
or younger?].
AB - Breast cancer in women 35 years old or younger is unusual. It accounts for 1-3.6%
of all breast cancers but is the leading cause of cancer mortality in women 15-35
years old. The diagnostic delay, with T2 or more advanced cancer at clinical
presentation, is due to the patient's age and the opinion of low mammographic
reliability for cancer diagnosis in this age group. To assess the usefulness of
mammography in breast cancer patients aged 35 years or younger, we reviewed the
clinical, mammographic and histologic data of 65 cancers collected in 7 breast
diagnosis and counseling centers in Lombardy. Fifty-three patients (81.5%) were
referred for a palpable breast mass, which was a T2 or more advanced cancer in 23
cases. Mammography showed malignant patterns (spiculated opacities, clusters of
microcalcifications, casting, branching and ductal type calcifications) in 31
patients (47.7%). Mammography was not definitive but correctly suggested further
examinations in 30 women and it had only 4 false negatives. Ultrasonography
performed in 43 patients was negative in 3 (7%), pathologic and pathognomonic for
cancer in 27 (62.8%) and pathologic but not indicative of malignancy in 13
(20.2%). The cytologic or histologic diagnosis of breast cancer was made under US
guidance in 24 cases. In women aged 35 years or younger mammography was effective
in identifying breast cancers; US and fine-needle aspiration biopsy (FNAB)
complete mammography. We believe that mammography can be a valuable screening
tool in young women at high risk for breast cancer because of family history.
PMID- 9638159
TI - [Angiography compared to high resolution magnetic resonance and digital
angiography in atherosclerosis of the iliac-femoral arteries].
AB - INTRODUCTION: Magnetic Resonance Angiography (MRA) potentials in all vascular
districts have been largely applied also to peripheral vessels, where however
there is no agreement as to the best type of sequence. We investigated the
sensitivity, specificity and diagnostic accuracy of 2D TOF travel-sat MRA in the
study of iliac-femoral artery stenoses. The gold standard was digital subtraction
angiography (DSA). MATERIAL AND METHODS: Twenty patients (14 men and 6 women,
mean age: 65 years with suspected atheromasic disease were examined. Diagnostic
MRA and DSA were carried out within 48 hours of each other. A super-conductive 1
T magnet (Siemens Impact) and a body coil were used. 2D TOF travel-sat sequences
were carried out with the following parameters: FA 40 degrees, TR 31 ms, ST 10
mm, overlap 1 mm, MA 128 x 512. The images acquired on the axial plane were
postprocessed with MIP on the z axis from -15 degrees to 15 degrees. Two
different radiologists evaluated MRA and DSA images and graded the stenoses on a
multiple choice card: 1) negative, 2) 1-40%, 3) 41-70%, 4) 71-99%, 5) occlusion.
RESULTS: MRA diagnosed 90 positives and 110 negatives: 60 were true positives, 92
true negatives, 30 false positives and 18 false negatives. MRA overestimated 8
cases and underestimated 4 cases. DSA findings were negative in 122 cases and
positive in 78 cases: 4 grade 2, 10 grade 3, 28 grade 4 and 36 grade 5. Relative
to DSA, MRA sensitivity, specificity and diagnostic accuracy were 72%, 75% and
74%, respectively; MRA diagnostic accuracy, sensitivity and specificity in
hemodynamically severe stenoses (> 71%) were 80%, 78% and 71.8%, respectively.
CONCLUSION: Our study confirms the usefulness of 2D TOF travel-sat MRA in the
study of iliac-femoral stenoses.
PMID- 9638160
TI - [Stenosis-occlusion of the carotid bifurcation. Angiography with MR and contrast
media versus digital angiography].
AB - PURPOSE: To evaluate the comparative sensitivity, specificity and diagnostic
accuracy of contrast enhanced magnetic resonance angiography (CE MRA) and digital
subtraction angiography (DSA) in the study of carotid bifurcation stenoses.
MATERIAL AND METHODS: Twenty-three patients with suspected cerebrovascular
insufficiency by carotid stenosis were examined with CE MRA and DSA within 24
hours of each other. A 1.5 superconductive unit (Signa, General Electric) was
used for CE MRA; fast spoiled gradient echo recalled (SPGR) images were acquired
on the coronal plane 12 s after contrast medium injection, with the following
parameters: TR/TE/FA 8/1/60, MA 256 x 128, NEX 1, FOV 18 x 13, slices/slab 28,
slice thickness 1 mm, TA 32 s. The images were postprocessed with the maximum
intensity projection (MIP) and the targeted MIP algorithms. A Siemens Politron
1000 VR unit was used for DSA examinations. RESULTS: DSA diagnosed 21 true
positives, namely 4 grade II, 4 grade III, 10 grade IV and 3 grade V stenoses. CE
MRA scored 100% in stenosis identification and grading, accurately diagnosing all
the true negatives and the true positives and was always in agreement with DSA as
to stenosis site. CONCLUSION: CE MRA can be considered the technique of choice to
study stenosis occlusion in the epiaortic vessels, because it permits a rapid
panoramic study of the neck vessels and accurate stenosis grading with similar
patterns to those of DSA. Thus, CE MRA appears to be a valid alternative to DSA.
PMID- 9638161
TI - [Radiologic assessment of transpyloric spread of gastric carcinoma].
AB - PURPOSE: We report on our personal experience with the radiologic and CT
demonstration of the traspyloric duodenal spread of gastric carcinoma, whose
relative frequency and prognostic value are recent literature data. MATERIAL AND
METHODS: In the last 4 years we submitted to double contrast studies of the upper
gastrointestinal (GI) tract 49 gastric carcinoma patients with antrum
involvement. Twenty-one cases were staged with CT performed with gastric water
distension, pharmacological hypotonia and dynamic contrast agent perfusion.
Finally, 41 patients underwent surgical treatment. RESULTS: Radiologic evidence
of transpyloric gastric carcinoma spread was found in 6 cases; CT, performed in 5
of them, was always in agreement. Five of 6 positive cases had surgical
confirmation while one lesion was unresectable. No radiologic or CT false
negatives were found among the remaining 36 surgical patients. Barium studies
showed irregular antral lumen narrowing, rigid, open and eccentric pyloric
channel, duodenal bulb deformity and irregular thickening. CT demonstrated antrum
infiltration along the two gastric curvatures and the tumor spread to the
duodenal cap. CONCLUSION: Antral cancer transpyloric spread is more frequent than
previously reported and its presence should not exclude a carcinomatous process.
Double contrast barium studies are a valuable tool in the demonstration of this
spread, showing good correlation with CT staging findings.
PMID- 9638162
TI - [Nine consecutive patients with gallstone ileus. Personal experience].
AB - INTRODUCTION: Gallstone ileus is a mechanical obstruction of the gastrointestinal
tract caused by the impaction of one or more gallstones within the bowel lumen.
The insidious clinical presentation and the lack of specific signs of biliary
disease are responsible for the delayed preoperative diagnosis which leads to an
overall mortality rate of 15%. MATERIAL AND METHODS: A series of 9 consecutive
patients (7 women and 2 men, age ranging from 17 to 83 years), with surgically
proved gallstone ileus, was retrospectively reviewed: the authors report the
radiologic procedures performed preoperatively and the diagnostic findings. Plain
abdominal radiographs were performed in 4 of 9 patients, abdominal US in 4 and CT
in 7 patients. All radiologic examinations were retrospectively reviewed by all
authors independently, to recognize the different signs of gallstone ileus.
RESULTS: The signs of Rigler's triad (small bowel obstruction, ectopic gallstones
and air in the biliary tree) were observed on plain abdominal films in two cases,
and ectopic gallstones and pneumobilia in two cases. The ectopic gallstones and
the small bowel obstruction were demonstrated on abdominal US images in three
cases. Rigler's triad was identified on abdominal CT images in 4 cases, while two
findings (small bowel obstruction and ectopic gallstones) were observed in three
cases. CONCLUSIONS: When the bowel is obstructed by a radiopaque calcified stone,
plain radiographs and US of the abdomen are usually enough to diagnose gallstone
ileus and no further studies are required.
PMID- 9638163
TI - [Prostatic volume: suprapubic versus transrectal ultrasonography in the control
of benign prostatic hyperplasia].
AB - INTRODUCTION: During the follow-up of benign prostatic hypertrophy, the urologist
needs the repeated evaluation of the gland size to monitor the effectiveness of
drug treatment. We investigated the comparative adequacy of transabdominal and
transrectal US for prostatic measurements, to possibly replace the gold standard
transrectal examination with cheaper, easier and less invasive transabdominal
studies. MATERIAL AND METHODS: February, 1994, to May, 1996, we submitted 196
patients to prostate US, with a transabdominal convex probe and a transrectal
biplanar probe. The three prostatic diameters were measured and prostatic volume
and height calculated. RESULTS: The transverse diameter was the same (+/- 5%) in
31.6% of cases, but transabdominal US overestimated it in 41.8% and
underestimated it in 26.5% of cases. The AP diameter was the same in 33.1% of
cases, but trans-abdominal US overestimated it in 15.3% and underestimated it in
51.5% of cases. The cranio-caudal diameter was the same in 25.5% of cases, but
transabdominal US overestimated it in 59.1% and underestimated it in 15.3% of
cases. Consequently, the volume calculated with transabdominal US was the same
(+/- 15%) in 27.5% of cases, overestimated in 45.9% and under-estimated in 26.5%
of cases; prostatic weight rates were about the same. CONCLUSIONS: Prostatic
volume and weight measured with transabdominal US are overestimated in about 50%
of cases and are the same (+/- 15%) in about 27% of cases only. Therefore,
transabdominal US appears less reliable than transrectal US for prostatic
measurements and the latter technique remains the gold standard to monitor drug
treatment effectiveness in benign prostatic hypertrophy follow-up.
PMID- 9638164
TI - [Incidence and functional role of antithyroid antibodies in hyperthyroidism].
AB - INTRODUCTION: We report our personal experience in patients with biochemical
hyperthyroidism and no nodules, studying the correlations between antithyroid
autoantibodies titers, thyroid function and clinical symptoms. MATERIAL AND
METHODS: We examined 93 patients (13 men and 80 women, mean age: 44.6 years,
range: 25-68 years) referred for suspected hyperthyroidism. Thyroid 99mTc
scintigraphy was performed and the 20 minutes' uptake index (UI) calculated: all
these patients had a scintigraphic pattern of normal or enlarged thyroid with
homogeneous radiotracer uptake. The presence and titer of antiperoxidase (TPO)
and anti-TSH receptor antibodies (TRAB), FT3, FT4, TSH were assayed. Based on the
results, the patients were divided into 4 subgroups: A (high TRAB/high TPO, no.
17), B (low TRAB/high TPO, no. 15), C (high TRAB/low TPO, no. 35), D (low
TRAB/low TPO, no. 26). The incidence of hyperthyroidism symptoms was 94% in Group
A, 40% in Group B, 89% in Group C, 50% in group D. RESULTS: UI significantly
correlated with FT3 (p < .001), FT4 (p < .01) and TRAB (p < .01) titers. FT3 and
UI average values were significantly higher in Group A and Group C patients (high
TRAB) than in Group B and Group D patients (low TRAB) (p < .01); these parameters
were significantly higher also in Group A than in Group B patients (p < .05 for
FT3 and p < .03 for UI, respectively). Mean intergroup TSH values did not differ
(p = ns) and anti-TPO antibodies did not correlate with FT3, FT4 and TSH titers.
CONCLUSIONS: UI behaved as a good marker of hyperthyroidism in all patients and
TRAB correlated well with organ function and the clinical picture; however, about
18% of patients exhibited no antibody production. No correlation was found
between TPO and thyroid function. The lack of antithyroid antibodies seems to
indicate a better clinical course for hyperthyroidism. The patients without TRAB
and/or with high anti-TPO titers may follow different clinical courses and need a
regular follow-up.
PMID- 9638165
TI - [Ultrasonography, with Doppler color, and cytologic correlations in Plummer's
disease].
AB - PURPOSE: We carried out a retrospective study to assess the different B-mode and
color Doppler features of Plummer's disease and to compare them with cytologic
findings. MATERIAL AND METHODS: One hundred and eighty autonomous nodules were
studied with B-mode US. Mean patient age was 55 years for women and 56 years for
men. Twenty-seven patients were also submitted to color Doppler US. Forty-nine
autonomous nodules were also submitted to cytologic examination by fine needle
aspiration (FNA). RESULTS: The most frequent US pattern was a hypoechoic solid
nodular lesion (59.8%), while 45.6% of the nodules exhibited a mixed US pattern.
No mixed areas were found in 100% of the nodules in the patients under 20 and
over 60. In contrast, various degrees of mixed areas were found in the patients
20-59 years old, with the highest rate (24.9%) in the 40-49 age range and the
lowest rate (6.2%) in the 20-29 age range. The mixed areas were most frequently
correlated with bigger nodules and the toxic phase. Calcifications were found in
4.3% of the partially autonomous nodules in 4.1% of the pretoxic nodules and in
8.6% of the toxic nodules. Color Doppler US showed rich internal and peripheral
vascularization (pattern A) in 74.1% of the nodules and a mostly perilesional
flow (pattern B) in 25.9% of the cases. Pattern A prevailed in the toxic phase
(75%), while pattern B in the partially autonomous nodules (85.7%). Simple
hyperplasia was the most frequent (63.3%) cytologic feature in the solid nodular
lesions, while bleeding (10.2%) was typical of the mixed anechoic nodular
lesions. Cytologically undifferentiated lesions were found in the toxic phase of
Plummer's disease (50%). DISCUSSION: Solid lesions in Plummer's disease are
characterized by hyperplasia, while the diagnosis of hemorrhagic pseudocyst is
typical of mixed lesions. CONCLUSIONS: Color Doppler US provides data on the
functional phase of Plummer's disease and is a very useful tool to monitor
medical treatment results; moreover, it permits to characterize the lesions with
the richest vascularization, avoiding inadequate cytologic sampling.
PMID- 9638166
TI - [Magnetic resonance in the study of suprarenal neoplasms. Qualitative and
quantitative analysis of signal intensity].
AB - INTRODUCTION: Magnetic Resonance Imaging (MRI) has been proposed as the
diagnostic technique of choice to characterize adrenal tumors. However, the
results of the current studies are controversial. MATERIAL AND METHODS: Forty
nine patients with unilateral adrenal masses were submitted to MRI for lesion
characterization on the basis of MR signal intensity. Cytology and/or histology
demonstrated 14 pheochromocytomas (pheos), 11 adenomas, 3 cysts, 2 myelolipomas,
4 carcinomas, 3 metastases and 1 fibrosarcoma; a clinical diagnosis of adenoma
was made in the remaining 11 patients. MR studies were performed using spin-echo
(SE) sequences with T1 (TR/TE = 600/17 ms) and T2 (TR/TE = 2000/15-90 ms)
weighting. T1-weighted images were also acquired after Gadolinium-DTPA (Gd-DTPA)
administration. MR studies were integrated with in- and out-of-phase (TR/TE =
100/4-6 ms) chemical-shift (CS) sequences. MR signal intensity (SI) was analyzed
qualitatively and quantitatively; MR results were correlated with tumor type and
hormone secretion. RESULTS: The qualitative analysis of T2 images showed high
signal intensity in the majority (80%) of adrenal lesions (14 pheos, 12 adenomas,
3 cysts, 2 myelolipomas and 8 malignancies). The quantitative analysis of post-Gd
DTPA T1 images permitted to distinguish adenomas, cysts and myelolipomas from
pheos and malignancies. The qualitative analysis of post-Gd-DTPA T2 and T1 images
permitted to distinguish pheos and cysts from adenomas and malignancies (p <
.05); however, pheos and cysts as well as adenomas and malignancies were not
differentiated. MR SI was similar in secreting and nonsecreting adenomas from
both a qualitative and a quantitative viewpoints. CS MRI permitted to distinguish
adenomas (decreased signal intensity on out-phase relative to in-phase images)
from other benign and malignant lesions (no signal change from out-phase to in
phase images). CONCLUSIONS: The qualitative analysis of MR SI on conventional T1
and T2 images does not permit to differentiate adrenal masses. The qualitative
evaluation of T1 images after Gd-DTPA administration, the quantitative analysis
and CS sequences are technical options improving lesion characterization.
PMID- 9638167
TI - [Subtraction magnetic resonance angiography. Description of a new technique].
PMID- 9638168
TI - [Intra-arterial antiblastic treatment of breast carcinoma].
AB - PURPOSE: To report our personal experience with the locoregional treatment of
breast cancer. MATERIAL AND METHODS: Eighteen patients aged 33-67 years (mean: 54
years) were treated with 31 sessions of intra-arterial antiblastic infusion, 5 of
them for neoadjuvant purposes (Group 1), 5 for palliation in unresectable tumors
(Group 2) and 8 for cutaneous recurrences after mastectomy (Group 3). RESULTS:
2/5 CR and 3/5 PR were obtained in Group 1; 2/5 lesions were made resectable and
3/5 RP obtained in stage III or unresectable lesions (Group 2). Finally, 3/8 CR,
3/8 PR, 1/8 SD and 1/8 PD were observed in Group 3. An objective response
according to WHO criteria was demonstrated in 15/18 cases (88%). We had no post
treatment hematologic complications, but one patient presented focal subcutaneous
sclerosis and one cutaneous necrosis. CONCLUSIONS: The morphological efficacy of
intraarterial antiblastic infusion in our series was similar to that of other
series. No definitive conclusions can be drawn yet about clinical results and
long-term survival. This poorly invasive and low risk procedure, which should be
combined with other treatments, permits to reduce the extent of surgery and to
treat skin recurrences.
PMID- 9638169
TI - [Multiple bilateral biopsy of the prostate].
AB - INTRODUCTION: Transrectal guided biopsy is the method of choice to detect
carcinoma of the prostate. Systematic bilateral biopsies have been recently
introduced in clinical practice because they provide valuable information about
the local staging of the cancer and better representation of the actual Gleason
grade of the whole tumor. The purpose of this study is to assess the frequency of
neoplastic lesions in prostatic areas with normal structure at US and rectal
examination and to identify, if possible, some criteria to be used in the
selection of patients for random biopsies. MATERIAL AND METHOD: Systematic
bilateral prostatic biopsies were performed in 155 patients with elevated
prostate specific antigen (PSA) values, not exceeding 40 ng/mL and with suspected
neoplastic unilateral lesion at rectal examination or US. All patients with
bilateral or diffuse nodules were not included in this analysis. Three random
biopsies for every side of the gland were performed using a 16-18 gauge tru-cut
needle. A direct biopsy of the hypoechoic nodule or area was always performed.
All specimens results were correlated with PSA and PSA density values obtained
before biopsy. RESULTS: Systematic biopsy identified cancers in 53/155 patients
(34.19%). Of 53 cases, 35 (66%) had unilateral prostatic carcinoma and 18 (34%)
had bilateral cancer. The final diagnosis was benign prostatic lesion in the
remaining 102 patients (benign prostatic hyperplasia, nonspecific granulomatous
prostatitis, chronic prostatitis). Dividing all the patients into main groups on
the basis of pathologic findings (benign, unilateral and bilateral carcinoma)
there was a statistically significant difference of PSA values between the 3
groups. CONCLUSIONS: Our observations confirm the utility of systematic US-guided
biopsies in the detection of tumors in normal appearing areas at US and
transrectal examination, but the clinical utility of this approach needs further
confirmation. Additional data on cancer volume, Gleason grade, capsular
infiltration, lymph node metastasis and long term survival must be evaluated with
large number of patients. In our experience PSA values can be used as a criterion
to select the patients to submit to this technique to provide useful,
preoperative information suspected prostatic malignancy.
PMID- 9638170
TI - [Diagnostic imaging of the salivary glands in patients undergoing radiotherapy of
head and neck neoplasms].
AB - INTRODUCTION: Radiotherapy of head and neck cancers changes the shape and
function of the salivary glands included in the treated region. We investigated
the morphological and functional alterations in the major salivary glands in 15
patients treated with radiotherapy for head and neck cancers (total dose: 55-66
Gy). MATERIAL AND METHODS: All the patients underwent B-mode and power Doppler
US, CT and 99mTC salivary scintigraphy, before, at the end, and 60-80 days after
radiotherapy. RESULTS: At the end of treatment, US showed irregular margins and
inhomogeneous parenchymal echogenicity in 13 parotid and in eight submandibular
glands. Doppler US showed of focal hyperemia and focally decreased or no
intraparenchymal flow in nine parotid and in two submandibular glands. CT
demonstrated parenchymal inhomogeneity with increased and decreased density
areas, cancers irregular margins, and gland atrophy in 15 parotid and in eight
submandibular glands. Salivary scintigraphy depicted injuries of the major
salivary glands detecting their reduced pertechnetate uptake in 12 parotid and in
eight submandibular glands, with a decreased drug excretion in 12 parotid and in
12 submandibular glands. DISCUSSION AND CONCLUSION: Our findings confirm that the
major salivary glands are affected by radiotherapy, which makes their
morphological and structural monitoring of vital importance. US is the technique
of choice for its low cost and easy execution, and it is well accepted by the
patients because it requires no exposure to ionizing radiations. Power Doppler
provided no relevant information, but it confirmed the high resistance of small
and middle caliber vessels after radiotherapy. Scintigraphy clearly showed the
glands involvement demonstrating decreased uptake technetium secretion and
excretion. In conclusion, US and CT are both extremely useful in the study of the
morphological changes of the major salivary glands.
PMID- 9638171
TI - [Use of filgrastim, granulocyte colony stimulating factor (G-CSF), in
radiotherapy to reduce drop-outs because of radiogenic leukopenia].
AB - Radiotherapy patients are at risk of developing leukopenia, which risk depends on
the irradiated volume, the rate of irradiated bone marrow and the radiation dose.
Radiogenic leukopenia may cause radiotherapy drop-out, with consequent effects,
on local tumor control and clinical outcome. The introduction of granulocyte
growth factors, such as filgrastim, has permitted to accelerate normal neutrophil
count recovery in irradiation-related neutropenia both in vitro and animal
models; clinical experience in humans is still lacking, relative to both
indications and scheduling. In the Oncologic Radiotherapy Department of Treviso
Hospital, 31 patients irradiated for Hodgkin disease, rectal cancer and other
malignancies, who presented leukopenia requiring treatment discontinuation, were
given filgrastim to assess its actual effect in avoiding further drop-outs and to
compare two administration schedules (2 or 3 vials, 30 MIU, weekly). Filgrastim
treatment was continued throughout the radiotherapy cycles, for 1 to 5 weeks.
Eighteen patients had received previous chemotherapy and 11 were undergoing
concurrent 5-fluorouracil chemotherapy-irradiation. A mean 203% increase in
leukocyte count was observed (136% in the patients treated with 2 vials/week and
274% in those receiving 3 vials/week); this increase was more apparent in women
that in men (256% versus 91%) and slightly higher in patients 50 years old and
with target volumes < 5000 ml. Filgrastin treatment was well tolerated by all
patients, with no discontinuations due to adverse effects; 9 patients (29%)
reported skeletal pain, which was marked in 2 of them only. Eighty percent of
patients completed all the radiotherapy cycles with no discontinuation, while 6
patients dropped out because leukopenia persisted. Biweekly filgrastim
administration was effective to prevent unscheduled radiotherapy discontinuation
in 75% of patients and triweekly administration was effective in 86% of patients.
In our experience, filgrastim administration was well tolerated and effective in
decreasing the irradiation drop-outs caused by treatment-related leukopenia.
Since this drug is rather expensive, we decided to use routinely the lower dosage
of biweekly administration (with one vial given on Friday and Saturday, to permit
neutrophil recovery during the day off) and to reserve the higher dosage (3 vials
a week) to the patients with large body areas, big target volumes and persistent
leukopenia during previous chemotherapy.
PMID- 9638172
TI - [Multiple hemangiopericytoma of the left ankle and foot. Magnetic resonance study
and surgical findings in a case].
PMID- 9638173
TI - [Necrotizing fasciitis of the neck: report of a case and review of the
literature].
PMID- 9638174
TI - [Intracystic papilloma of the male breast associated with monolateral
gynecomastia. Clinicopathological findings in a case].
PMID- 9638175
TI - [Hypoplastic left ventricular syndrome: report of a case studied with magnetic
resonance in the preoperative period].
PMID- 9638176
TI - [A case of abdominal aortic coarctation studied with angiography and magnetic
resonance].
PMID- 9638177
TI - [A case of spontaneous aorto-caval fistula demonstrated with spiral computerized
tomography].
PMID- 9638178
TI - [Role of cholangiopancreatography combined with magnetic resonance and
hepatobiliary scintigraphy with 99mTc-HIDA in the assessment of biliary
dyskinesia. Report of a case].
PMID- 9638179
TI - [Retained surgical sponge mimicking bladder neoplasm. Report of a case and
diagnostic assessment with ultrasonography and computerized tomography].
PMID- 9638180
TI - [A lung opacity like any other].
PMID- 9638181
TI - [Scintigraphy of somatostatin receptors in gastropancreatic tumors].
PMID- 9638182
TI - A perspective on controlling cat populations.
PMID- 9638183
TI - Bioengineering and food animal veterinarians.
PMID- 9638184
TI - What is your diagnosis? Nasal lymphoblastic lymphosarcoma causing epistaxis in a
dog.
PMID- 9638185
TI - Agents, vehicles, and causal inference in bacterial foodborne disease outbreaks:
82 reports (1986-1995).
AB - OBJECTIVE: To examine the study design of, and the practice of causal inference
in, investigations of bacterial foodborne disease outbreaks occurring in the
United States and to summarize agents and vehicles identified. DESIGN:
Retrospective study. PROCEDURE: An online medical reference database was searched
for reports of bacterial foodborne disease outbreak investigations published
between 1986 and 1995. Reports were retrieved and reviewed for use of 9 causal
criteria in investigations. Information on etiologic agents, vehicles,
seasonality, and primary study design from each outbreak was also retrieved.
RESULTS: 82 reports were retrieved and reviewed. Coherence, consistency,
temporality, and strength of association were the causal criteria most commonly
used in foodborne disease outbreak investigations. Coherence was used in all
investigations. The number of criteria used ranged from 3 to 7. Meat (n = 20) and
eggs (12) were the most commonly implicated vehicles. Salmonella sp and
Escherichia coli O157:H7 accounted for 55% of agents reportedly isolated. Cohort
and case-control methods were the most common study designs. CLINICAL RELEVANCE:
Patterns were found in the use of causal criteria in foodborne disease outbreak
investigations. These criteria can provide veterinarians and other public health
practitioners with a means to effectively conceptualize, communicate, and
summarize causal conclusions. The 4 most commonly used criteria may represent
core criteria that investigators consider most useful in explaining food-borne
disease outbreaks.
PMID- 9638186
TI - Effect of intracameral administration of carbachol on the postoperative increase
in intraocular pressure in dogs undergoing cataract extraction.
AB - OBJECTIVE: To determine whether intracameral injection of carbachol at the
completion of phacoemulsification in dogs would prevent the increase in
intraocular pressure (i.o.p) that can develop during the first 24 hours after
surgery. DESIGN: Randomized controlled trial. ANIMALS: 32 adult dogs undergoing
elective unilateral or bilateral phacoemulsification. PROCEDURE: Dogs were
randomly assigned to 1 of 4 groups with 8 dogs/group: phacoemulsification and
intracameral administration of 0.5 ml of 0.01% carbachol at the end of surgery;
phacoemulsification, intraocular lens implantation, and intracameral
administration of 0.5 ml of 0.01% carbachol; phacoemulsification and intracameral
administration of 0.5 ml of balanced salt solution; and phacoemulsification,
intraocular lens implantation, and intracameral administration of 0.5 ml of
balanced salt solution. Intraocular pressure was measured at 3 and 6 hours and
the morning after surgery. Aqueous flare was also measured 6 hours and the
morning after surgery. RESULTS: None of the dogs treated with carbachol developed
postoperative ocular hypertension (i.e., IOP > 27 mm of Hg), whereas 12 of 16
control dogs had ocular hypertension 3 hours after surgery. Intraocular pressure
3 hours after surgery was not significantly associated with phacoemulsification
time or phacoemulsification power or with whether the dog received an intraocular
lens implant. Severity of aqueous flare was similar for treated and control dogs.
CLINICAL IMPLICATIONS: Results suggested that intracameral administration of
0.01% carbachol at the end of surgery was a safe and efficacious method of
preventing the postoperative increase in IOP associated with phacoemulsification
in dogs.
PMID- 9638187
TI - Association between hyperadrenocorticism and development of calcium-containing
uroliths in dogs with urolithiasis.
AB - OBJECTIVE: To determine, among dogs with urolithiasis, whether dogs that had
hyperadrenocorticism would be more likely to have calcium-containing uroliths
than would dogs that did not have clinical evidence of hyperadrenocorticism.
DESIGN: Retrospective case-control study. ANIMALS: 20 dogs that had urolithiasis
and hyperadrenocorticism and 42 breed-matched dogs that had urolithiasis but did
not have clinical evidence of hyper-adrenocorticism. PROCEDURE: Signalment,
urolith composition, results of bacterial culture of urine, and results of
adrenal axis tests were recorded. A multivariate logistic regression model was
created, including terms for age, sex, and hyperadrenocorticism. The outcome
variable was presence or absence of calcium-containing uroliths. RESULTS: Among
dogs with urolithiasis, those that had hyperadrenocorticism were 10 times as
likely to have calcium-containing uroliths as were dogs that did not have
clinical evidence of hyperadrenocorticism (odds ratio, 10.5; 95% confidence
interval, 1.5 to 23.4). Neutered and sexually intact females were less likely to
have calcium-containing uroliths than were neutered males (odds ratios, 0.041
[95% confidence interval, 0.0057 to 0.29] and 0.024 [95% confidence interval,
0.0012 to 0.51, respectively). CLINICAL IMPLICATIONS: Prompt diagnosis and
treatment of hyperadrenocorticism may decrease prevalence of calcium-containing
uroliths in dogs.
PMID- 9638188
TI - Apparent primary ossification of the menisci in a dog.
AB - A 2-year-old Collie was examined after it developed acute lameness in the right
hind limb. Palpation of the right stifle elicited signs of pain, but a cranial
drawer sign could not be elicited during palpation of the joint. Radiography
revealed mineralized opacities in the craniolateral and caudal portions of the
right stifle joint. Exploratory arthrotomy of the right stifle joint revealed a
firm mass in the cranial horn of the lateral meniscus, which was characterized as
osseous metaplasia in the cranial and caudal menisceal horns on histologic
examination. Other abnormalities were not identified during surgery. Results of
histologic examination, radiologic evidence, and observations during exploratory
surgery supported a diagnosis of primary lateral meniscal ossification of the
right stifle joint. Radiographs were obtained of the contralateral stifle joint
when the dog was clinically normal (5 weeks after arthrotomy), and mineralized
opacities were found in the lateral meniscus of this limb as well. Clinical signs
may not be associated with primary intrameniscal ossification initially; type and
location of ossification may affect likelihood and severity of clinical signs and
secondary joint damage. Initial treatment for menisceal ossification is
conservative (anti-inflammatory medications) unless there is a concurrent
pathologic process that requires surgical repair.
PMID- 9638189
TI - Hepatocellular toxicosis associated with administration of carprofen in 21 dogs.
AB - A diagnosis of hepatocellular toxicosis attributable to carprofen administration
was made in 21 dogs on the basis of development of clinical signs and
clinicopathologic abnormalities associated with hepatic disease and
histopathologic documentation of hepatic necrosis. Clinical signs of toxicosis
were anorexia, vomiting, and icterus. Hyperbilirubinemia and high serum
activities of alanine transaminase, alkaline phosphatase, and aspartate
transaminase were the most notable clinicopathologic abnormalities. In 7 of 9
dogs in which urinalyses were performed, abnormalities suggestive of renal
tubular disease were detected. Clinical course of toxicosis was variable;
however, most dogs had resolution of clinical signs and improvement or resolution
of biochemical abnormalities with discontinuation of the drug and administration
of supportive care. As with any medication, clients should be informed of
possible adverse effects and reactions associated with administration of
carprofen. In the event of those signs, clients should be instructed to
immediately discontinue administration of carprofen to their dog and contact
their veterinarian.
PMID- 9638190
TI - Prognostic factors for dogs with granulomatous meningoencephalomyelitis: 42 cases
(1982-1996).
AB - OBJECTIVE: To assess signalment, clinical signs, results of CSF analysis,
treatment, and survival times in dogs with granulomatous meningoencephalomyelitis
(GME) and to identify factors associated with survival. DESIGN: Retrospective
study. SAMPLE POPULATION: Medical records of 42 dogs with GME. PROCEDURE:
Information on signalment, neurolocalization, presence of focal or multifocal
signs, results of CSF analysis, method of treatment, and time from onset of
clinical signs to death was retrieved from medical records of each dog. Kaplan
Meier survival analysis was used to assess survival times. The Cox proportional
hazards method was used to identify predictors of survival. RESULTS: Females and
toy and terrier breeds were predisposed to GME. Half of the dogs had focal
neurologic signs, and half had multifocal involvement. Clinical signs referable
to the forebrain were most common with focal involvement, whereas signs referable
to the forebrain and brainstem were most commonly seen with multifocal
involvement. Cerebrospinal fluid analysis commonly revealed a mononuclear
pleocytosis. Survival times ranged from 1 to > 1,215 days. Significant
differences in survival times were demonstrated for the following factors: focal
versus multifocal clinical signs, neurolocalization of focal signs, and treatment
with radiation. Radiation was the only independent predictor of survival.
CLINICAL IMPLICATIONS: Dogs with signs suggesting focal involvement of GME tend
to survive longer than those with multifocal involvement. Radiation is an
effective treatment for dogs with GME, particularly those with clinical signs
suggesting focal involvement.
PMID- 9638191
TI - Results of double-contrast cystography in cats with idiopathic cystitis: 45 cases
(1993-1995).
AB - OBJECTIVE: To determine results of double-contrast cystography in cats with
idiopathic cystitis. DESIGN: Retrospective study. ANIMALS: 45 cats with clinical
signs of nonobstructive lower urinary tract disease for which an underlying cause
could not be determined. PROCEDURE: Medical records and double-contrast
cystograms performed initially and during 6- and 12-month reevaluations were
reviewed. RESULTS: 105 cystograms were reviewed. Fifteen (33%) cats had
abnormalities evident on cystograms obtained at the time of initial examination.
Of these, only 1 had abnormalities 6 and 12 months later. Thirty cats did not
have abnormalities evident on cystograms obtained at the time of initial
examination. Of these, 1 had abnormalities on a cystogram performed 6 months
later and another had abnormalities on a cystogram performed 12 months later.
Abnormalities evident on cystograms included focal thickening of the bladder wall
(n = 11), diffuse thickening of the bladder wall (6), irregularities of the
bladder mucosa (10), decreased opacity of the bladder wall (3), increased opacity
of the bladder mucosa (3), filling defects (4), contrast medium in unexpected
locations (3), and altered ureteral opacity (15). CLINICAL IMPLICATIONS: Results
suggested that a large percentage of cats with idiopathic cystitis do not have
cystographic abnormalities when initially examined but that abnormalities may be
apparent during follow-up evaluations. In addition, a smaller percentage of cats
with idiopathic cystitis may have nonspecific cystographic signs of cystitis or
hemorrhage. Leakage of contrast medium into the peritoneal space during
cystography does not necessarily require surgical management.
PMID- 9638192
TI - Development and duration of antibody response against Ehrlichia equi in horses.
AB - OBJECTIVE: To characterize antibody response in horses with clinical signs of
Ehrlichia equi infection. DESIGN: Prospective study. ANIMALS: 13 horses with
confirmed acute E equi infection. PROCEDURE: Sequential serum sampling was
performed in Connecticut and New York during 1995 and 1996 to identify horses
with naturally acquired equine granulocytic ehrlichiosis (EGE). Horses with
clinical signs of EGE (i.e., fever without respiratory involvement) were
confirmed as having E equi infection by polymerase chain reaction detection of
ehrlichial DNA and by a minimum fourfold increase in total antibody titer by
indirect fluorescent antibody staining methods. Infection was corroborated by use
of DNA sequencing. RESULTS: 11 of 13 horses did not have detectable antibody in
serum samples obtained at onset of disease. Seroconversion was evident in samples
obtained 19 to 81 days thereafter. Median time to peak antibody response was 46
days after onset and median titer was 1:320. For 11 of 13 horses, antibody titers
were < or = 1:40 by 215 days after onset. CLINICAL IMPLICATIONS: E equi was found
in horses in the northeastern United States and caused EGE. Concentration of
antibodies to E equi increased within 19 to 81 days of disease onset and were low
during early weeks of infection. Therefore, antibody detection may be of limited
value for early serologic diagnosis. We suggest that disease may develop from a
reinfection, and retrospective serologic studies to determine exposure to E equi
may reflect a disproportionate number of negative reactions.
PMID- 9638193
TI - Primary hyperparathyroidism caused by a functional parathyroid adenoma in a
horse.
AB - A 14-year-old Arabian gelding had weight loss and anorexia of 3 weeks' duration.
Results of repeated laboratory tests revealed persistent hypercalcemia and serum
phosphorus concentration that was within or less than the reference range.
Parathyroid hormone concentration was high. Histologic examination of specimens
obtained at necropsy revealed parathyroid adenoma. A diagnosis of primary
hyperparathyroidism attributable to a functional parathyroid adenoma was made.
Abnormalities in calcium and phosphorus concentrations were similar to those seen
with primary hyperparathyroidism in dogs, in which this syndrome is best
described. Primary hyperparathyroidism should be considered to be a potential
cause of hypercalcemia in horses in which other more common causes of
hypercalcemia, such as humoral hypercalcemia of malignancy, nutritional secondary
hyperparathyroidism, chronic renal failure, vitamin D toxicosis, and bony or
granulomatous disease, are ruled out.
PMID- 9638194
TI - Effects of tilmicosin on acute undifferentiated respiratory tract disease in
newly arrived feedlot cattle.
AB - OBJECTIVES: To evaluate effects of tilmicosin when used in fever-based and
metaphylactic treatment programs to attenuate acute undifferentiated bovine
respiratory disease (BRD) in cattle that recently arrived at feedlots, and to
evaluate the effects of tilmicosin for the treatment of BRD. DESIGN: Randomized
block controlled study. ANIMALS: 1,639 calves from livestock auctions.
PROCEDURES: Cattle were assigned to 3 groups. Cattle in the nonmedicated
(control) group were not given antibiotics during processing. Cattle in the fever
based treatment group were given tilmicosin (10 mg/kg [4.5 mg/lb] of body weight,
s.c.) during processing when their rectal temperature was > or = 40 C (104 F).
All cattle in the metaphylactic treatment group were given tilmicosin (10 mg/kg,
s.c.) during processing. Calves with BRD were treated with tilmicosin (10 mg/kg,
s.c.). RESULTS: Morbidity rates in the metaphylactic (30.4%) and fever-based
(44.7%) treatment groups were less than that for the nonmedicated group (54.8%).
Mortality rate for the metaphylactic group during the first 28 days (1.1%) and
during the entire study (1.7%) was less than that for the nonmedicated group (3.3
and 4.6%, respectively). Differences were not observed in therapeutic response
rates among calves with BRD that were treated. CLINICAL IMPLICATIONS: Fever-based
and metaphylactic treatment programs that used tilmicosin decreased the
prevalence of BRD and improved growth of calves. Metaphylactic treatment
decreased the number of fatalities caused by BRD in high-risk calves. Fever-based
treatment was less effective than metaphylactic treatment for decreasing the
prevalence of BRD in newly arrived cattle.
PMID- 9638195
TI - Isolation of Salmonella serotypes from feces of pigs raised in a multiple-site
production system.
AB - OBJECTIVE: To determine the prevalence and serotypes of Salmonella organisms in
feces of pigs raised in a modern, multiple-site production system. DESIGN: Cross
sectional study of prevalence. SAMPLE POPULATION: Swine housed on 7 farms (1 gilt
development farm, 2 breeding farms, 1 nursery farm, and 3 finishing farms) that
formed a multiplesite production system. PROCEDURE: Fecal samples were obtained
from 792 pigs (96 to 202/farm) and submitted for bacteriolgic culture of
Salmonella organisms. RESULTS: Salmonellae were isolated from pigs on all 7 farms
and from 95 of 792 (12%) fecal samples. Prevalence ranged from 3.4% at the gilt
development farm to 18 and 22% at the breeding farms. Serotypes identified were
Salmonella derby, S typhimurium var. copenhagen, S heidelberg, S typhimurium, S
mbandaka, S worthington, and S tennessee. No single serotype was not isolated
from all the farms of the production system and the most prevalent serotypes at
the 3 finishing farms (S typhimurium or S typhimurium var. copenhagen) were not
isolated from the breeding or nursery farms. CLINICAL IMPLICATIONS: Upstream
infection (pigs infected before arriving at finishing farms) appears to be an
unimportant source of Salmonella infection of finished hogs in multiple-site
systems. High prevalence of Salmonella shedding in breeding animals suggests that
food products derived from culled breeding livestock may be an important source
of foodborne disease.
PMID- 9638196
TI - [Characteristics of ischemic heart disease patients with late ventricular
potentials].
AB - The purpose of this study was to compare ischemic heart disease (IHD) patients
with and without late potentials (LP) by using noninvasive diagnostic methods as:
echocardiographic examination, exercise testing, 24-hours Holter ambulatory
monitoring, recording of atrial and ventricular signal-averaged ECG. Examination
covered 25 IHD pts (12 male and 13 female) with LP, mean age 58.6 +/- 7.3 (group
I) and 100 IHD pts (65 male and 35 female) without LP, mean age 56.8 +/- 8.5
(group II). Summing up, it should be stated that despite showing tendencies to
much often occurrences of ventricular arrhythmias on Holter monitoring and silent
ischemia during exercise testing in IHD pts with LP we were unable to indicate
distinctive differentiating parameters between investigated groups.
PMID- 9638197
TI - [Evaluation of treatment effectiveness for Helicobacter pylori infections in
children].
AB - An assessment was performed of the effectiveness of treatment of Helicobacter
pylori infection and coexisting diseases in children with two and three drugs. A
high percent of bacterial eradication and cure of the coexistent conditions were
achieved particularly in the group of children treated with three drugs.
PMID- 9638198
TI - [Study of nitroblue tetrazolium reduction by granulocytes in workers handling x
ray equipment].
AB - In 44 persons (25 women and 15 men), workers handling X-ray equipment in X-ray
laboratories the ability was studied of nitroblue tetrazolium (NBT) reduction by
neutrophils. The obtained results were compared with a control group. Besides
that subgroups were isolated taking into account the sex of the studied subjects
and duration of their work with X-ray equipment (over five years and below five
years). In the workers handling X-ray equipment and in the isolated subgroups of
women and men, the index of spontaneous NBT reduction turned out to be
statistically significantly higher than that in the control group. In the group
of studied workers the index of latex-stimulated NBT reduction was statistically
significantly lower than that in the control group. Taking into account the
duration of work with X-ray equipment in the subgroups of women and men working
for over five years, the lowest index of phagocytes was noted. On the basis of
the obtained results the following conclusions were formulated: 1. In workers
handling X-ray equipment disturbances occur of peripheral blood neutrophil
metabolism assessed in the NBT test. 2. Neutrophil phagocytic activity is
weakened in persons working over five years with X-ray equipment.
PMID- 9638199
TI - [Usefulness of transcutaneous oximetry in vascular surgery].
AB - The assessment is presented of the value of transcutaneous oximetry in vascular
surgery and in choosing the level of ischaemic limb amputation. Transcutaneous
measurements of oxygen pressure (tcp02) were performed in 172 patients operated
on for chronic ischaemia of the lower limbs before and three weeks after the
operation. The studied subjects had the following operations done: bifurcated or
unilateral aortofemoral bypass, femoropopliteal bypass, restoration of patency of
the iliac and femoral arteries, lumbar sympathectomy, lower limb amputation. The
studies were carried out using Hellige SM 361 oxymonitor and a similar Polish
device. For oximetric measurements superficial skin sensor (Clark's polarographic
electrode) was used, which was applied into the dorsum of the foot and medial
crural surface. Transcutaneous oximetry seems to be a useful method for the
assessment of the results of operations restoring blood flow in lower limb
arteries. It makes possible to evaluate the results of lumbar sympathectomy.
Transcutaneous measurements of oxygen pressure are also a useful method for the
assessment of results of amputation of chronically ischaemic lower limb.
PMID- 9638200
TI - [Evaluation of fear and analysis of personality structure of women at risk for
premature and after term labor].
AB - Psychological studies were performed in 57 pregnant women at risk for premature
labour and 36 at risk for after term labour. The level of fear was evaluated
using the Spielberger STAI questionnaire. The structure of fear and restlessness
was studied using the R.B. Cattell's five factor Self-estimation Sheet. The
analysis of personality structure was performed on the basis of results of the
MMPI-WISKAD test. In the patients in both studied groups, groups an increased
level of situational and persistent fear was found. Women at risk for premature
labour are characterized by higher level of fear of neurotic character resulting
from disharmonious personality. In women delivered after term the fear is of
reactive character. Women at risk for after term labour are characterized by a
higher degree of personality integration and more effective ability to control
fear. Women at risk for premature labour are characterized by disharmonious
personality and simultaneously they use more primitive protective mechanisms.
Women delivered after term are characterized by higher degree of personality
integration and more effective ability to control fear.
PMID- 9638201
TI - [Evaluation of some hemodynamic indices in 15 to 18 year old boys with lipid risk
factors for atherosclerosis].
AB - The aim of the work was an attempt at answering the question whether there is any
correlation between the haemodynamic indices describing arterial elasticity
assessed by physical analysis of the circulatory system and lipid risk factors
for arterial atherosclerosis in boys aged 15 to 18 years. The studies included 45
boys with lipid risk factors for atherosclerosis. The control group included 53
boys without lipid risk factors. In boys aged 17-18 years with lipid risk factors
for atherosclerosis as compared with their peers with normal serum lipid level, a
statistically significant change of arterial elasticity was found. A positive
correlation was also found between the increased serum cholesterol level and the
values of air-chamber elasticity index and peripheral vascular resistance, and a
negative correlation was demonstrated between the decreased serum HDL-cholesterol
concentration and the increase of pulse wave velocity in the aorta, air-chamber
elasticity index and peripheral vascular resistance.
PMID- 9638202
TI - [Profiles of daily secretion of ACTH, beta-endorphins and cortisol in patients
after minor craniocerebral trauma].
AB - In 12 men aged 20-25 men who had minor craniocerebral trauma the profiles of
daily secretion of ACTH, beta-endorphin and cortisol were studied. The studies
were carried out on the second day after the trauma. Plasma concentrations of the
hormones were determined on 8.00, 12.00, 17.00 and 22.00 hours. Statistically
significantly increased, in relation to healthy persons, (p < 0.01) values of
plasma hormone concentration were found at all time points. In 50% of the
patients (six cases) a disturbance was found of the profile of daily secretion of
ACTH and beta-endorphin. The disturbance of the profile of cortisol secretion was
found only in one patient.
PMID- 9638204
TI - [Carcinoid--advances in diagnosis and treatment].
AB - Carcinoid is one of the most frequently diagnosed neuroendocrine tumours. It
develops slowly but grows by infiltration and has the ability to give metastases
in distant organs. The clinical picture is very diverse and in 10% of cases the
signs called carcinoid syndrome develop. Not infrequently it produces also
peptide hormones. In the present paper the most modern diagnostic methods,
possibilities of surgical and pharmacological treatment of this extremely
interesting neoplasm are discussed.
PMID- 9638203
TI - [Iatrogenic esophageal perforation].
AB - A total of 213 patients with a foreign body in the oesophagus was treated in our
unit between 1980-1990. Most of the foreign bodies were impacted in the cervical
oesophagus. Oesophagoscopy were carried out under general anaesthesia in all
cases. iatrogenic perforation of oesophagus was encountered in ten cases. Our
results suggest that most instrumental perforation of the esophagus should be
managed surgically. Drainage and closure of cervical perforations yields good
results. Nonoperative management night be entertained in minimally symptomatic
patients harboring a late, locally contained perforation without signs of ongoing
sepsis.
PMID- 9638205
TI - [Differential diagnosis of enlarged scrotum].
PMID- 9638206
TI - [Spa treatment of urogenital system diseases].
AB - Attention was paid to the underestimated value of spa treatment of urinary system
diseases. The methods of this type of therapy, and indications and
contraindications in the treatment of urological diseases are discussed. Such
therapy accelerates recovery, has prophylactic values and reduces the cost of
treatment.
PMID- 9638207
TI - [Coexistence of Pneumocystis carinii infection with pertussis].
PMID- 9638208
TI - [Use of salazopyrin in Schonlein-Henoch disease].
AB - A favourable effect was achieved of treatment with salazopyrin of severe
abdominal of Schoenlein-Henoch disease (SH). Salazopyrin was used in two children
with generalized form of SH, with paroxysmal abdominal pain and bleeding from the
gastrointestinal tract.
PMID- 9638209
TI - [Iatrogenic uretero-vaginal fistula].
AB - A case is presented of iatrogenic late ureterovaginal fistula treated with
ureteral transplantation with a very good result. It was found that this was the
method of choice in this type of fistulae, and temporary internal ureteral
splinting was worthwhile to use as a prophylaxis of iatrogenic ureteral damage.
PMID- 9638210
TI - [Evaluation of ciliary epithelium cilia in diagnosis of Kartagener syndrome].
AB - A case of 41 year man with Kartagener's syndrome presenting incomplete clinical
symptoms of disease was described. Diagnosis was established by electron
microscopy analysis of nasal mucous membrane cilia biopsy. Ultrastructurally the
complete lack of dynein arms was found.
PMID- 9638211
TI - [Foreign body in the frontal sinus].
AB - The authors describe the case of the foreign body in frontal sinus left there
after prior surgery. The case was treated surgically with good results.
PMID- 9638212
TI - [Bioethical aspects of ecology and medicine in an industrialized society].
PMID- 9638213
TI - [II. Physicians and their practice].
PMID- 9638214
TI - [Activity of beta-hexosaminidase in serum of patients with alcoholic and
nonalcoholic liver diseases].
AB - The total activity and thermostable activity of serum beta-hexosaminidase were
determined in alcohol-dependent patients with liver damage, in non-drinking
hepatic patients, in alcohol-dependent presently drinking patients who had no
hepatic symptoms and signs, and in healthy persons drinking alcohol occasionally
in moderate quantities who served as the control group. The enzyme activity was
determined by the spectrofluorometric method using 4-methylumbelliferone
derivative as substrate. The activity of beta-hexosaminidase in both groups with
liver disease of both alcoholic and non-alcoholic origin exceeded significantly
the control values. In those alcohol-dependent patients with liver disease who
did not stop drinking, the activity was higher after recent drinking in relation
to that after a period of abstinence. The determination can thus serve as a
marker of alcohol abuse also in alcohol-dependent patients with liver damage. The
share of thermostable component in the total increase of beta-hexosaminidase
activity in alcohol-abusing persons was higher than that in the case of hepatic
diseases of non-alcoholic origin.
PMID- 9638215
TI - [Duphalac (lactulose) in the treatment of chronic constipation in children].
AB - The aim of this study was to estimate the effectiveness of DUPHALAC preparation,
produced by Solvay-Pharma, in treatment of functional chronic constipation. 112
children, aged 10 months-15.5 years were examined. DUPHALAC appeared to be very
effective, were examined. Only two patients did not accept its taste. Rapidly
(approximately after 2.5 weeks) improvement was achieved such as of restoration
normal peristalsis and of previously disturbed defecation rhythm, softening of a
stool, regression of pain and/or dyspeptic ailments, encopresis and improvement
of appetite. In no case undesirable side effects were observed.
PMID- 9638216
TI - [The value of anti-inflammatory effectiveness of Apranax 550 and Voltaren 50
after knee joint arthroscopic surgery].
AB - The results are presented of the study of the effectiveness of non-steroid anti
inflammatory drugs (Apranax, Voltaren) on the basis of observation of 60 patients
in a double blind trial after knee joint arthroscopic operations. The
administration of Apranax 550 or Voltaren 50 within the period of 10 days after
the operation decreased significantly the incidence of inflammatory reactions.
Apranax 550 was acting more rapidly and more effectively in elimination of
clinical signs and symptoms of inflammation, and the patients were not reporting
any adverse effects.
PMID- 9638217
TI - [Evaluation of treatment results for lateral ankle fractures].
AB - An analysis was performed of 18 lateral ankle fractures with fracture fissure
running from above-back forward and down-ward. In this group, 15 cases were
treated conservatively and three cases surgically. In eight patients an evident
limitation of pronation movements was found, the remaining movement being limited
to a lesser degree. In six patients traces after previous separation of
tibiofibular syndesmosis were found. The conservative treatment failed to
maintain normal conditions in the talocrural joint.
PMID- 9638218
TI - [Conservative treatment of calcaneal fractures].
AB - The results of conservative treatment has been presented in 19 patients treated
for calcaneal bone fracture. The most common changes are: 1--dislocation of
loading point; 2--disorder of foot statics; 3--degenerative and deformity causing
changes; 4--reduction of walking efficiency which made some patients change their
profession; 5--quite frequent recommendation to subtalar arthrodesis.
PMID- 9638219
TI - [Anxiety-depressive neurosis in ambulatory treatment conditions].
AB - A group of 48 patient was treated for fear and depressive neurosis at Psychical
Health Consulting Unit. They were observed and evaluated in period from April
5th, 1990 till December 31st, 1990. The group included 32 women and 16 men. The
conclusion is the women was 66.6% and the men 33.4%. 23 persons (47.9%) was
treated with Doxepin and 25 persons (52.1%) was treated with Alprazolam (Xanax,
Valeans). The administration of one medicine was the rule, in case of the failure
a medicine was change for another one. One used also individual psychotherapy.
PMID- 9638220
TI - [Endocrine ophthalmopathy--etiopathology].
AB - Endocrine ophthalmopathy is regarded as organ specific disease of
autoimmunological origin. It occurs most frequently in patients with Graves
disease, less frequently in those with Hashimoto thyroiditis. The presence of HLA
DR-3 and HLA b-8 antigens, cigarette smoking, treatment with radioiodine, and
thyroid function disturbances predispose for the development of the disease. On
the other hand, the most important pathogenetic mechanism is fibroblast
stimulation and increased collagen and glucosaminoglycans production within the
extrabulbar muscle interstitium.
PMID- 9638221
TI - [Diabetic osteopathy].
PMID- 9638222
TI - [Ototoxicity of drugs].
AB - The paper included the most current information about the mechanisms of
ototoxicity of five groups of the most popular drugs: a) antibiotics, b)
chemotherapeutics (cytostatic) agents, c) loop diuretics, d) salicylate and
nonsteroidal anti-inflammatory drugs, as well as e) progestagen contraceptives
minimized or even prevented by thoughtful selection of drug, attention to risk
factors and careful patient monitoring.
PMID- 9638223
TI - [Interstitial cystitis--diagnosis and etiopathogenesis].
PMID- 9638224
TI - [Alcoholic withdrawal delirium].
AB - The actual progress of medical studies, reach to 1% in comparison with former
data 20% a number of death in delirium tremens. The aim of this study is the
presentation the symptoms of alcohol psychosis, as well as of various methods of
it's cure. To choose of right therapy is sometimes very difficult for the
physician. In this work one tries to explain pathogenesis of delirium tremens.
Author's doctors of first contact in achieving right diagnosis and therapy.
PMID- 9638225
TI - [Scar changes in the bronchus caused by a foreign body].
AB - Long lasting recurrent pneumonia in 13-year-old girl was been described. The main
cause was the foreign body (pawn of plastic) covered in intermediate bronchus.
Bronchoscopy revealed scars in type of "bridges" narrowing intermediate bronchus.
The foreign body and the scar changes were removed.
PMID- 9638226
TI - [Lesniowski-Crohn disease in the esophagus].
AB - In the paper two cases are presented of Lesniowski-Crohn disease located in the
oesophagus. The clinical course, diagnosis and surgical treatment are described.
The attention is paid to the difficulties in differentiation of lesions
developing in the course of this disease from malignancy, exerting significant
influence on the choice of surgical management.
PMID- 9638227
TI - [High esophageal perforation in a 2.5 year old child].
AB - A case is presented of a 2,5-year-old child in whom high oesophageal perforation
developed after gastric lavage due to ingestion of lethal dose of salicylates.
Strong, locally irritating action of salicylates on the oesophageal mucosa was
demonstrated which, most probably, was the cause of the perforation.
PMID- 9638228
TI - [Foreign bodies in the bile ducts as a cause of jaundice].
PMID- 9638229
TI - [The development of hydrocephalus after intracranial hemorrhage in an infant with
meningoencephalitis].
AB - The present paper describes the case of hydrocephalic infant resulting from the
intracranial haemorrhage with coexisting meningitis. The evolution of brain
changes in sonography is shown.
PMID- 9638231
TI - [A case of primary pulmonary hypertension in a 52-year old man].
AB - The presented case of primary pulmonary hypertension is worth attention in view
of rare incidence in men, especially those over 50 years of age. It was possible
to observe the course of the disease and to perform examinations confirming the
diagnosis. The unavoidable and rapid progression of lesions, extremely poor
prognosis and lack of possibilities of causal treatment should be stressed.
PMID- 9638230
TI - [A case of Lyell's syndrome caused by carbamazepine].
AB - A case is described of Lyell syndrome in a female patient with schizoaffective
psychosis which developed several days after addition of carbamazepine to the
psychotropic treatment used. After withdrawal of the drug and three weeks of
treatment with prednisone in dose 60 mg daily, antibiotic therapy and intensive
dermatological-nursing care, full remission of skin lesions and oral mucosa
lesions was obtained.
PMID- 9638232
TI - [Hepatitis virus infection as a possible cause of cholangiopathy].
PMID- 9638233
TI - [I. Physicians and their practice].
PMID- 9638234
TI - [Historical outline of electrocardiography].
PMID- 9638235
TI - [Clinical picture of acute myocardial infarction depending on the use of
pharmacologic treatment schemes].
AB - The aim of the work was a retrospective comparison of the clinical course of
acute myocardial infarction depending on the applied schema of pharmacological
treatment: streptokinase, heparin, antiplatelet drugs. The analysis included 409
patients (261 men and 148 women aged 31-85 years; mean age 61 years). Twelve-lead
ECG records were analysed: 24 hours, 48 hours, 72 hours, 7 days and 14 days after
the onset of the disease. The sum of ST segment elevations, sum of Q wave
amplitude and the sum of R wave amplitude in the leads showing signs of
infarction were taken into account. The mean was calculated from the highest
values of AspAT and AlAT. The haemodynamic, arrhythmic and other early and late
complications occurring during the treatment were subjected to analysis; the per
cent index of deaths in each group was also calculated. In the patients treated
with streptokinase, in comparison to the patients treated with heparin and
antiplatelet drugs, earliest stabilization was observed of the ECG pattern in the
form of: reduction of ST segment elevation, reduction of R wave height, and
formation of a stable Q wave. AspAT and AlAT values were highest in the group of
patients treated with streptokinase in relation to the remaining groups of
patients. Arrhythmic and haemodynamic complications occurred less frequently in
the patients treated with streptokinase and heparin than in those treated with
antiplatelet drugs. On the other hand, late and other early complications were
observed less frequently in the patients treated with antiplatelet drugs. The
mortality during hospitalization period was similar in individual groups of
patients, being 7.2% for the patients treated with streptokinase, 7.5% for those
treated with antiplatelet drugs, and 9% for those treated with heparin.
PMID- 9638236
TI - [The influence of patient age on the effectiveness of bronchodilators].
AB - The beta adrenergic receptors are exposed to variety of factors modulating their
activity. We analyzed the sensitivity to Salbutamol in asthmatic patients divided
into three group (I-30 yr; II-30-50 yr; III-50 yr). The effectiveness of beta
adrenergic receptors was assessed by means of estimation of plasma cAMP level
before and after Salbutamol infusion. We didn't found any significant differences
in plasma cAMP changes between investigated group of patients.
PMID- 9638237
TI - [The effect of multiple plasmapheresis on levels of apolipoprotein B, fibrinogen
and cholesterol in blood donors].
PMID- 9638238
TI - [Evaluation of arrhythmia incidence during gastroscopy examination].
PMID- 9638239
TI - [Investigations in the use of mogramostime (GM-CSF) in patients with acute
leukemia].
PMID- 9638240
TI - [Treatment of advanced pancreatic cancer with interferon alpha, tumor necrosis
factor and 5-fluorouracil (preliminary report].
AB - This paper presents the first outcomes of a combined therapy of advanced cancer
of pancreas with Interferon alpha, Tumor Necrosis and 5-Fluorouracil. Every
subject underwent surgical treatment, but only in two cases partial resection was
done. In the other subject only palliative operations were performed because of
advances stages of neoplastic process. All patients were followed up during the
time ranged between from 2.5-13.5 months. Complete remission was observed in one
patient (survival time--9 months). In three subjects partial remission was
reported, whereas in the left part of our cohort the general condition was
steady. This research would be continued.
PMID- 9638241
TI - [Long term treatment results for chloride diarrhea].
PMID- 9638242
TI - [Evaluation of selected enzyme activity in neutrophils and in blood serum of x
ray technicians].
PMID- 9638243
TI - [Vaginal candidiasis in parturients].
PMID- 9638244
TI - [Biotherapy in hematology. Biology and clinical use of granulocyte colony
stimulating factor (G-CSF)].
AB - G-CSF is one of drugs which play important role as one of link of the long chain
used in biotherapy of cancers. However effect of G-CSF was known more than 20
years ago, it doesn't exclude chemotherapy and/or radiotherapy but it is
effective complementary of this methods. The purpose of this short review is to
describe biological activity, effects and clinical applications of G-CSF.
PMID- 9638245
TI - [The role of the thymus in the human body].
AB - The work deals with contemporary opinions on the endocrinological function of
thymus. The latest information concerning T cell maturation has also been
provided. It has been shown that there is a direct relationship between the
process of lymphocyte T proliferation and formation of the organism tolerance to
self. The current opinions dealing with the phenomenon of the thymus involution
have been given stressing its advantageous significance for human organism. The
work shows wide connections of the gland in question with other organs. The
participation of thymus in pathogenesis of some disease entities has also been
presented.
PMID- 9638246
TI - [Stimulation of fetal lung development].
PMID- 9638247
TI - [Pathophysiology of cerebral ischemia].
PMID- 9638248
TI - [Central nervous system infections in patients with AIDS].
AB - Central Nervous System (CNS) is very common site of the opportunistic infections
in patients with AIDS. Patients, who died because of AIDS have described
pathology of CNS in 80% in autopsy series. Toxoplasmic encephalitis (TE) is the
most common infection in the course of AIDS, and it touches 25-50% of the HIV
infected people. The treatment of TE is very difficult, but relapses are very
often and primary and secondary prophylaxis of TE is necessary. Fungal infections
(particularly cryptococcal meningitis) are very unpopular in immunocompetent
patients; in HIV-infected people Cryptococcus neoformans is the cause of the 30%
of encephalitis. Viral and bacterial encephalitis, they are not very common in
AIDS patients.
PMID- 9638249
TI - [Losartan, new angiotensin receptor antagonist--a challenge for enzyme converting
angiotensin inhibitors?].
PMID- 9638250
TI - [Malignant neoplasms of the small intestine as a cause of obstruction].
PMID- 9638251
TI - [Giant ovarian cyst in a 15-year girl].
PMID- 9638252
TI - [Endometriosis with colonic involvement].
PMID- 9638253
TI - [Vestibular neuritis in the course of a tick-borne viral meningitis infection].
PMID- 9638254
TI - [A case of leptospirosis with respiratory tract symptoms].
PMID- 9638255
TI - [III. Physicians and their practice].
PMID- 9638256
TI - The petrolingual ligament: the anatomy and surgical exposure of the
posterolateral landmark of the cavernous sinus.
AB - The petrolingual ligament is the posteroinferior attachment of the lateral wall
of the cavernous sinus, where the internal carotid artery enters the cavernous
sinus. The petrous segment of the internal carotid artery finishes and the
cavernous segment begins at the superior margin of this ligament. The ligament is
surgically important due to its identification as a landmark for dissection of
the internal carotid artery during the approaches to posterolateral
intracavernous and extracavernous lesions. It can be well exposed after
mobilization of the gasserian ganglion, or after the trigeminal root and ganglion
have been split along the junction of V2 and V3 (the transtrigeminal approach).
The petrolingual ligament was studied in five cadaveric head specimens from ten
sides. The size of the ligament was measured, and its anatomical, clinical and
surgical importance is discussed.
PMID- 9638257
TI - Supratentorial primitive neuroectodermal tumours: a report of four cases with an
unusual clinical course in one patient.
AB - Four children, who were treated for supratentorial primitive neuro-ectodermal
tumours between 1986 and 1995 at Kyushu University Hospital, are here presented.
The initial characteristic symptoms and signs of these patients included vomiting
and headache, followed by motor weakness. All patients underwent direct surgery
for their tumours while 2 also received a course of postoperative radio-therapy.
After these treatments, 3 died within 4 months after diagnosis, whereas one
infant, who underwent a total removal of the tumour but had no adjuvant therapy,
is still alive after a follow-up period of 4 years. Most of the tumour cells of
these 4 cases were poorly differentiated neuro-ectodermal cells, but some also
showed variable differentiation along the glial and/or neuronal lines. While such
differentiation had no impact on the clinical course of the patients, the
malignant potential as assessed by the percentage of MIB1-positive cells showed a
good correlation with the clinical features; the 3 cases with a rapid clinical
course had MIB1 staining indices of more than 2%, and one case, who survived more
than 4 years, had the same indices of 0.2% as found in benign tumours. Although
"PNETs" of Hart and Earl share certain clinical features, they may be a group of
tumours heterogeneous in their origins, histogenesis, and biological behaviours.
PMID- 9638258
TI - Functional magnetic resonance mapping of sensory motor cortex for image-guided
neurosurgical intervention.
AB - PURPOSE: This paper describes the potentials of functional magnetic resonance
imaging (fMRI) to map sensory motor cortex in patients with mass lesions near
primary motor cortex and to guide neurosurgical procedures located close to
eloquent brain regions. MATERIAL AND METHODS: 7 patients with mass lesions near
the central sulcus and 10 healthy volunteers were studied using a blood
oxygenation level dependent 2D multislice multishot T2* weighted gradient echo
EPI sequence on a 1.5T Phillips Gyroscan during alternating epochs of rest and
motor activation of hand, foot and tongue. Sites of neuronal activation were
identified by statistical analysis of the signal time course using Kolmogorov
Smirnov statistics. RESULTS: Neuronal activation following motor tasks
consistently localised to the contralateral precentral gyrus and the
supplementary motor area, even in the presence of local brain pathology.
Additionally we could observe activation in primary sensory areas (post-central
gyrus) and supplementary motor area (SMA) in some cases. CONCLUSION: fMRI is
capable of mapping sensory motor cortex even in the presence of distorting brain
lesions. Since this information will provide valuable information to the
neurosurgeon during pre-operative planning, we consider this method for
neurosurgical navigation a valuable tool in the routine diagnostic of
intracerebral interventions.
PMID- 9638259
TI - Haemodynamic evaluation of cerebral gliomas using XeCT.
AB - The purpose of this study was to characterize regional blood flow (BF) in
untreated cerebral gliomas (CG) using stable Xe-enhanced computed tomography
(XeCT). XeCT of 38 patients with untreated CG were analyzed and compared with CT
and magnetic resonance images (MRI) and histopathological findings. Individual
averaged BF values for tumour in 29 high grade gliomas (HGGs) and 9 low grade
gliomas (LGGs) were intermediate between averaged BF values for cortex and white
matter in the non-tumour bearing hemisphere. All averaged BF values for cyst and
central necrosis were very low. In 27 HGGs, BF in tumour was relatively high in
ring-enhancement lesions on CT and MRI, but was low even in viable tumour centers
showing no contrast enhancement. In the other 2 HGGs, BF was low in tumour center
and relatively high in tumour periphery regardless of homogeneous enhancement. In
5 HGGs, averaged BF value of the cortex outside surrounding oedema was higher
than that of cortex in the non-tumour bearing hemisphere. In LGGs, BF
distribution in tumour was homogeneously low in 3 small-sized and heterogeneous
in 6 large-sized lesions including moderately high and low BF regions. These
differences in BF pattern between HGGs and LGGs on XeCT might be helpful in
considering to some extent the histopathology of untreated cerebral glioma pre
operatively.
PMID- 9638260
TI - Intraoperative facial nerve monitoring (IFNM) predicts facial nerve outcome after
resection of vestibular schwannoma.
AB - Intraoperative facial nerve monitoring (IFNM) is a suitable technique for
intraoperative facial nerve identification and dissection, especially in large
vestibular schwannomas (VS) (acoustic neuroma). To evaluate its feasibility for
estimating functional nerve outcome after VS resection 60 patients underwent
surgery using IFNM. Out of this group the last 40 patients were included in a
prospective study evaluating the prognostic value of various IFNM parameters
(proximal and distal absolute EMG amplitude, stimulation threshold, and proximal
to-distal amplitude ratio) for prediction of initial postoperative facial nerve
function and recovery of function. Stimulation threshold and absolute EMG
amplitude proximally at the brain stem were both predictive for postoperative
nerve function. Good initial facial nerve outcome (modified House Brackmann
grading, mHB degree I and degree II) was found in 15/16 patients with a proximal
EMG amplitude greater than 800 microV and in 19/22 patients with proximal
stimulation threshold less than 0.3 mA. Sixteen of 16 patients with proximal
stimulation threshold equal to or greater than 0.3 mA had moderate-to-severe
facial palsy (mHB degree III or worse). Six of six patients without evokable
proximal amplitude initially had insufficient nerve function (mHB degree IV).
Intraoperative decrease of the proximal amplitude was associated with an
unfavourable outcome, whereas distal amplitudes usually stayed unchanged. Mean
distal EMG amplitudes were also found to be decreased with poor nerve function,
which may mean that the tumour had already affected the nerve. A proximal
amplitude of 300 microV or less and a proximal-to-distal amplitude ratio below
1:3 were found in the absence of functional recovery in 6/8 (75%) and 5/6 (83%)
patients with initial mHB degree IV, respectively. Two patients with initial mHB
degree IV improved to mHB degree III despite intraoperative evidence of missing
functional nerve integrity. Therefore, functional recovery cannot be predicted by
IFNM in all cases of anatomical nerve preservation. We conclude that a minimum
follow-up period of 1 year may still be advisable even in certain patients
without evidence of intraoperative functional nerve integrity.
PMID- 9638261
TI - Subjective complaints versus neuropsychological test performance after moderate
to severe head injury.
AB - Neuropsychological test performance and subjective complaints of 85 patients with
moderate to severe head injury were investigated at 6 months postinjury. The
neuropsychological test battery included 10 measures of attention, memory, mental
flexibility, reaction time, visuoconstruction and verbal fluency. Subjective
complaints were assessed using a self-report questionnaire subdivided into four
subscales (somatic, cognitive, emotional and behavioural). Ratings were obtained
for the pre-injury and current status. Thirty-three trauma patients with injuries
to other parts of the body than the head were used as controls. For the head
injured, relatives also completed the questionnaire. Head injured patients
performed significantly below trauma control patients on nearly all test
measures. Head injured patients and their relatives reported a significant
increase in subjective complaints since the injury on all four subscales, with no
differences between patients' and relatives' reports. These changes were also
reported by the trauma controls, but they report fewer changes in somatic and
cognitive functioning. Exploratory canonical correlation analyses revealed no
correlations between any of the four scales of the questionnaire and the test
measures, nor for the head injured, the trauma controls, or the relatives,
indicating no relevant relationship between subjective complaints and
neuropsychological test performance.
PMID- 9638262
TI - Profuse hemorrhage from cerebral vessels in tangential missile injuries.
AB - Tangential missile injuries are recognized as a cause of cerebral damage by in
driven bone fragments, parenchymal lacerations and intracerebral haematomas.
Severe blood loss from this type of injury was not reported. Four patients are
described in whom high kinetic energy missiles caused severe tangential
craniocerebral injuries. Their condition was aggravated by life threatening
haemorrhage. The bleeding vessels were cerebral arteries or major veins entrapped
in the fracture line and bleeding extracranially. This blood loss cannot be
controlled by dressing and salvage could be achieved only by immediate
resuscitation, vigorous fluid replacement and very rapid evacuation to a
neurosurgical center.
PMID- 9638263
TI - Local hypercoagulative activity precedes hyperfibrinolytic activity in the
subdural space during development of chronic subdural haematoma from subdural
effusion.
AB - The involvement of coagulation and fibrinolysis in the development of chronic
subdural haematoma (CSH) from subdural effusion was investigated. Subdural fluid
and venous blood samples were obtained from 34 patients with CSH and 9 patients
with subdural effusion, and analyzed using enzyme-linked immunosorbent assays for
thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2),
tissue factor, tissue factor pathway inhibitor (TFPI) and D-dimer. CSH was
classified into the layering type, believed to be active, and other types
according to x-ray computed tomography. All markers in the blood of both patient
groups were similar to the values of normal subjects. Levels of TAT and F1 + 2
were much higher in the subdural fluid than in the blood of patients with CSH (P
< 0.001, P < 0.001) and with subdural effusion (P < 0.05, P < 0.05). The level of
D-dimer in the subdural fluid was significantly higher than in the blood (P <
0.001) in patients with CSH, but not in patients with subdural effusion. All
markers in the subdural fluid of layering type CSH, except TFPI, were
significantly higher than in the other types (P < 0.05). Local hypercoagulative
activity in the subdural space is present in subdural effusion and precedes
hyperfibrinolytic activity in CSH. Thrombin generation as indicated by TAT and F1
+ 2 might be involved in the development of CSH. Propagation of CSH may be
modulated by the coagulation system including the extrinsic pathway and
fibrinolysis.
PMID- 9638264
TI - A surgical technique for a vertebral column autograft using the intervertebral
disc for cervical disc disease.
AB - We describe a surgical technique for a vertebral column autograft using the
intervertebral disc for cervical disc disease for patients whose major problem is
not spinal instability. Of a total of 41 patients with cervical disc disease
suffering from cervical spondylotic radiculomyelopathy, 33 patients were operated
on at one level and 8 patients were operated on at two levels. Postoperative X
ray film showed some movement at the "operated" disc level in all patients
(average postoperative follow-up period was 43 months, range two years to 5
years). A significant decrease in motion in the extension position was observed
postoperatively (p < 0.0001), but no significant difference was observed between
the preoperative motion and the postoperative motion in the flexion position.
Anterior angulation was found in two (5%) of the 41 patients. This surgical
procedure has two major advantages: 1) no complications related to the iliac
donor site, allowing early patient mobilization; 2) the extensive posterior spur
can be removed safely and easily under a wide operative field. We believe that
this surgical procedure is suitable for preserving the mobility of the spine and
may avoid stress concentration at adjacent levels of the "operated" disc.
However, in patients whose major problem is spinal instability, anterior cervical
fusion should be performed.
PMID- 9638265
TI - Cellular dynamics of macrophages and microglial cells in reaction to stab wounds
in rat cerebral cortex.
AB - To examine the cellular dynamics of macrophages and microglial cells in response
to cerebral injury, we studied the brain adjacent to cortical stab wounds in
young adult rats. Brains were obtained 30 min after intravenous infusion of
bromodeoxyuridine (BrdU) on one day (day 1) to 28 days (day 28) after wounding.
Brain sections were double-labelled immunohistochemically for monocyte/macrophage
antigen ED1 and for BrdU. ED1-positive (ED1+) cells were classified
morphologically into two groups, ED1+L and ED1+S cells, representing macrophages
and microglial cells, respectively. ED1+L cells appeared on day 1 after wounding
and rapidly increased in number to reach a maximum on day 3, but quickly
disappeared by day 5. ED1+S cells also appeared on day 1, but the increase in
number was slower, reaching a maximum only on day 7. ED1+L cells were all
negative for BrdU, but some ED1+S cells were stained for BrdU, evidence of
proliferation. The present investigation demonstrated different cellular dynamics
for macrophages and microglial cells responding to a stab wound, and also
indicated differing sources for the two cell type. It may be possible to prevent
the accumulation of these cells which are harmful to the brain in reducing the
damage suffered.
PMID- 9638267
TI - Intraspinal air: an unusual finding of cervical epidural abscess.
PMID- 9638266
TI - Multiple intracerebral haemangioblastomas in identical twins with von Hippel
Lindau disease--a clinical and molecular study.
AB - Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant neoplastic
disorder causing central nervous system haemangioblastomas. The VHL gene (3p25
3p26) is known to be a tumour suppressor gene, with its inactivation being
responsible for a predisposition to tumour development. As far as we know, the
present report of VHL disease manifestation in identical twins is unique. Genetic
inquiry into the family background did not reveal this disease among their
progenitors. For presymptomatic diagnosis of 17 presently unaffected family
members, constitutional DNA of the twins was screened for VHL germline mutations,
using loss of heterozygosity studies and exon-specific DNA sequencing. To
determine the influence of somatic mutations of the VHL gene in tumourigenesis,
DNA of five surgically removed intracerebral haemangioblastomas of the identical
twins was analyzed in comparison with their constitutional DNA by DNA sequencing
of the complete VHL coding region. However, no allelic losses were found for the
VHL gene or for various other tumour suppressor genes (p53, BRCA1, BRCA2, DCC,
and MCC). Furthermore, no mutations were found in the constitutional DNA of
either twin sister or in the DNA of all five tumour lesions. Based on our
observations, we conclude that in certain VHL families, presymptomatic molecular
diagnosis of the disease is not feasible and requires close clinical surveillance
of all individuals at risk.
PMID- 9638268
TI - Mycotic aortic aneurysm presenting as multiple cerebral abscesses.
AB - A 68-year-old male presented with multiple cerebral abscesses. Possible
intrathoracic embolic sources were not detected by echocardiography and chest
radiography and the main lesion was surgically excised. Following deterioration
of the neurological status, computerized tomography performed 2 weeks later
revealed a mycotic aneurysm of the ascending aorta, probably related to a
previous cardiac operation. This is the first case in the literature of aortic
infection presenting as multiple brain abscesses.
PMID- 9638269
TI - Psammomatous meningioma arising from the diaphragma sellae.
PMID- 9638270
TI - A case of non-functioning pituitary adenoma accompanied by a large cyst.
PMID- 9638271
TI - Haematological changes in N'Dama and Gobra Zebu bulls during Trypanosoma
congolense infection maintained under a controlled feeding regimen.
AB - Haematological changes were monitored in Gobra-Zebu and N'Dama bulls following
infection with Trypanosoma congolense. The cattle were offered a diet which
provided levels of protein and energy above maintenance requirement and a pair
feeding regimen was used in order to eliminate the confounding anorexic effects
of trypanosomosis on the traits studied. Packed red cell volume (PCV), red blood
cells (RBC) and haemoglobin (Hb) were monitored weekly. Mean corpuscular
haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and mean
corpuscular volume (MCV) were derived by computation. Significant breed
differences (P < 0.001) were observed in the baseline data collected with N'Dama
bulls having higher (P < 0.001) values for RBC and Hb. PCV levels were similar in
both breeds pre-infection. Post-infection, there was a significant (P < 0.001)
infection effect on the RBC, Hb and PCV in both breeds. The pathogenic effects
were more severe in the Gobra-Zebu bulls where three out of ten bulls compared
with only one out of eight infected N'Dama bulls attained the low PCV threshold,
treated and withdrawn from the study along with their pair mates. Throughout the
infection in N'Dama cattle and during the first 6 weeks of infection in the Gobra
Zebu bulls, the infection presented a normochromic normocytic anaemia. However,
in the chronic phase, the Gobra-Zebu bulls became macrocytic. The infection
reduced total dry matter intake in both breeds although this persisted longer in
the Gobra-Zebus. However, their pair-fed controls showed no haematological
changes indicating that the anorexia was not compounding the effects of the
infection. The severity and type anaemia in N'Dama correlates with their innate
ability to resist the effects of trypanosome infection compared to the Gobra-Zebu
bulls.
PMID- 9638272
TI - The genomic fingerprinting of the coding region of the beta-tubulin gene in
Leishmania identification.
AB - We have demonstrated the polymorphism of the beta-tubulin gene region in
Leishmania and its value in the identification of the parasite. In this work we
have shown that the coding region of the gene has sufficient variation to
accurately discriminate these parasites at the subgenus level. Nevertheless,
intrasubgenus diversity, for particular restriction enzymes, was found in New
World Leishmania belonging to the Leishmania subgenus. For instance, differences
were found between mexicana and amazonensis strains. A unique pattern at the
species level was found in particular species of both subgenera, e.g. L. (L.)
major strain P and L. (L.) tropica belonging to the Leishmania subgenus, and L.
(V.) panamensis strain LS94 from the Viannia subgenus. Particular endonucleases
are diagnostic in Leishmania species discrimination as in the case of PvuII for
the mexicana and amazonensis. This variation evidenced in the beta-tubulin gene
region of Leishmania also occurred in other Kinetoplastida e.g. Trypanosoma
cruzi, Leptomonas spp. and Crithidia spp. Moreover, these organisms showed a
different genomic fingerprinting for the beta-tubulin gene among them and also
Leishmania. Thus, the polymorphism of the coding region of the beta-tubulin gene
can be used as a molecular marker for the identification of Leishmania.
PMID- 9638273
TI - Activity of N,N-dimethy-1-2-propen-1-amine derivatives in mice experimentally
infected with Trypanosoma cruzi.
AB - Propenamine derivatives 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N
dimethyl-2-prope n-1-amine (where X = H or Br) were tested in experimentally
infected mice with Trypanosoma cruzi (Y strain). When a daily dose of 20 mg kg-1
of the bromo (X = Br) derivative for 9 consecutive days was used, no parasite by
optical microscopy was found. Significant parasitemic decrease was also observed
with a single dose (100 mg kg-1) of this compound. Moreover, both treatment
schemes displayed a strong protective effect characterized by decreased of
mortality. On the other hand, similar treatment schedules using the unsubstituted
(X = H) derivative led to parasitemic and mortality curves similar to the control
group. These results indicate that the bromo derivative has a remarkable activity
against T. cruzi infection. Due to the potentiality of this derivative, further
investigation of this class of compounds as chemotherapeutic agents for Chagas'
disease is of prime importance.
PMID- 9638274
TI - Relationship between Borrelia burgdorferi sensu lato species, red squirrels
(Sciurus vulgaris) and Ixodes ricinus in enzootic areas in Switzerland.
AB - The infection and reservoir status of red squirrels (Sciurus vulgaris) for
Borrelia burgdorferi sensu lato were studied in Switzerland. B. burgdorferi sensu
lato was isolated from 15 skin samples from 4/6 dead red squirrels, victims of
road traffic. Isolates were identified using restriction fragment length
polymorphism (RFLP): B. burgdorferi sensu stricto was present in 14 culture tubes
containing skin samples and B. afzelii in two other tubes. A mixed infection was
revealed in one case. A total of 227 ticks attached to squirrels were cultivated
in BSKII medium and 90 isolates were obtained. Genotypic identification by RFLP
showed that B. afzelii (59%) and B. burgdorferi sensu stricto (46%) dominated in
ticks feeding on red squirrels. Data collected from one particular animal, highly
infested with Ixodes ricinus and harbouring numerous Borrelia-infected Ixodes
ricinus ticks, showed that transmission of B. burgdorferi sensu lato occurred
from S. vulgaris to feeding ticks. More precisely, B. burgdorferi sensu stricto
and B. afzelii were mainly transmitted from S. vulgaris to ticks. The present
data emphasized the results obtained previously from small rodents and birds in
Japan and in Switzerland, showing the occurrence of specific associations between
host species and Borrelia genospecies.
PMID- 9638275
TI - Cutaneous and subcutaneous granulomata formation in mice immunized and challenged
with third-stage infective hookworm (Ancylostoma caninum) larvae.
AB - To determine the inflammatory and immunological mechanisms associated with live
third-stage (L3) hookworm larval vaccines, mice were immunized either
subcutaneously or orally with three doses of 500 L3 of Ancylostoma caninum at 2
week intervals, and then challenged percutaneously (via abdominal skin) with 500
L3. Non-immunized mice served as negative controls. Skin was excised from post
challenge mice at intervals between 6 h and 28 days, and then examined by light
microscopy. In non-immunized mice the L3 exhibited no structural damage and
infiltrating inflammatory cells were absent from the surrounding tissues. There
were no changes in the cutaneous architecture. In contrast, skin recovered from
the immunized mice was edematous and exhibited marked inflammatory changes with
resultant destruction of the challenge L3. At 6 h post-challenge the L3 exhibited
cuticular swelling and damage; the surrounding tissue was infiltrated by
polymorphonuclear inflammatory cells. By 24 h granulomata in the dermis,
subcutaneous tissues and underlying abdominal muscles were first observed
surrounding dead L3. The number of granulomata peaked at 72 h, with the majority
distributed in the subcutaneous tissues. Plasma cells predominated in the early
granulomata, but by 3-7 days post-challenge foreign body giant cells began to
appear. In some cases, intact and presumably living L3 were noted in the
abdominal muscles 14-28 days post-challenge, which suggested that protection
against larval challenge was not absolute. Granuloma formation appears to be a
major component of the post-vaccination murine host immune response against
challenge larvae. The observation generates several hypotheses to investigate the
mechanisms of protection afforded by living helminth vaccines.
PMID- 9638276
TI - Biological characterization and genetic diversity of Mexican isolates of
Trypanosoma cruzi.
AB - The present work reports the in vitro biological characterization of 17
Trypanosoma cruzi isolates from southern and central Mexico, and compares these
results to those of four South American strains and one clone from Brazil. The
parameters evaluated were growth rates, percentage of parasites undergoing
transformation from epimastigotes to trypomastigotes, infectivity to, and in
vitro killing of cultured Vero and P388 cells. Isoenzyme patterns of 11 enzymatic
systems and 16 loci were also determined for the Mexican isolates. The parasites
showed differences in growth, depending if they were cultured in LIT with hemin
or in Grace's media. Transformation was obtained only in Grace's medium and
differences were observed between the stocks. Stocks Z10 and Z21 showed the
highest percentage of transformation within the Mexican isolates (39 and 41%,
respectively). A second group showed percentages of transformation between 15 and
28%. In contrast, the South American strains showed higher rates of
transformation (36-65%). Infection of cultured cells by isolates Z10 and H5 was
evaluated in both Vero and P388 cells. Differences were observed both in the
percentage of infected cells as well as in the number of amastigotes per cell.
Differences in the ability to cause in vitro killing of P388 cells were also
observed among the isolates. Isoenzyme analysis revealed genetic variation
between the isolates, each of them with an unique zymodeme. This genetic analysis
revealed, in general, a clustering based on the geographical origin of the
isolates. Finally, correlation with clinical symptoms is discussed.
PMID- 9638277
TI - Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii
nigeriensis infection in Swiss mice.
AB - The causal prophylactic activity of five tricyclic anti-histaminic agents
(histamine H1-receptor antagonists) cyproheptadine, ketotifen, loratadine,
azatadine and terfenadine was evaluated in an experimental murine malaria model.
Sporozoite induced infections with Plasmodium yoelii nigeriensis (N-67), a strain
innately resistant to choloroquine, were employed for the efficacy test and
pyrimethamine and primaquine were used as standard reference drugs. Treatment
with cyproheptadine or ketotifen at 5 mg/kg and terfenadine at 50 mg/kg, orally
for 3 days (-1, 0, +1) completely prevented the establishment of patent infection
in mice inoculated with 1 x 10(5) sporozoites on day 0. Partial activity was
recorded with lower doses of the above agents as well as with azatadine and
loratadine at 10 mg/kg as indicated by marginal delay in the development of
patent infection after sporozoite challenge. None of these agents showed blood
schizontocidal activity at doses found effective in the causal prophylactic test,
though initial suppression of parasitaemia was observed with cyproheptadine and
ketotifen at higher doses. This study is the first report on efficacy of
antihistaminic agents for growth inhibition of pre-erythrocytic stages of any
malaria parasite.
PMID- 9638278
TI - Response of a T. b. rhodesiense stock with reduced drug susceptibility in vitro
to treatment in mice and cattle.
AB - In vivo drug susceptibility tests involving treatment of infected mice and cattle
were performed on two trypanosome stocks, a T. brucei brucei and a T.b.
rhodesiense, isolated in South Eastern Uganda. The T. b. rhodesiense stock had
expressed reduced susceptibility to diminazene aceturate and isometamidium
chloride in vitro, while the other, a T. b. brucei stock was susceptible.
Diminazene aceturate at 14 mg/kg was not sufficient to cure all T. b. rhodesiense
infected mice. Similarly, in the case of isometamidium chloride, 33% of infected
mice treated with 2.0 mg/kg drug were not cured. In contrast, mice infected with
the susceptible T. b. brucei and treated similarly with either drug were all
cured. However, when cattle infected with the T. b. rhodesiense stock, or the
susceptible T. b. brucei stock, or a 1:1 mixture of the two were treated with 7
mg/kg diminazene aceturate, they were all cured. Use of diagnostic PCR employing
T. brucei specific primers confirmed that although the cattle had acquired
infection pre-treatment, no trypanosome DNA amplification signal was demonstrated
in the samples collected 60 days post-treatment. The reduced susceptibility of
this T. b. rhodesiense, which could be demonstrated in mice as well as in
culture, may indicate the existing potential for evolution of resistance in South
Eastern Uganda.
PMID- 9638279
TI - Gulf War syndrome--a model for the complexity of biological and environmental
interaction with human health.
AB - Since the end of the Gulf War, tens of thousands of American, Canadian and
British soldiers who participated in that war have claimed to be suffering from a
variety of incapacitating symptoms which are generally termed as Gulf War
Syndrome (GWS). The symptoms are multiple but mainly consist of excessive
tiredness, muscle and joint pain, loss of balance, sensory symptoms,
neurobehavioural manifestations, diarrhoea, bladder dysfunction, sweating
disturbances, and respiratory, gastrointestinal, musculoskeletal and skin
manifestations. These veterans have been exposed to a variety of damaging or
potentially damaging risk factors including environmental adversities, pesticides
such as organophosphate chemicals, skin insect repellents, medical agents such as
pyridostigmine bromide (NAPS), possible low-levels of chemical warfare agents,
multiple vaccinations in combinations, depleted uranium, and other factors. A
large number of basic research findings, clinical epidemiological studies, and
case control studies are reviewed to try and link them together to produce a
coherent picture and to demonstrate the complexity of the interaction of
biological systems, environmental and genetic factors, combinations of drugs and
toxins with human health. The findings of these studies so far have demonstrated
that many of the previous assumptions made about the 'safety' of certain drugs
and toxic substances or vaccines must be radically reviewed. Many of the findings
have far reaching implications not only in terms of explanation of what might
have gone wrong during the Gulf War, but also have wider implications for many
occupational groups who are exposed daily to some of these risk factors. More
open-mindedness and much less prejudice are required concerning the basic biology
of interactions of the above factors and their effects on cell functions and
wider intelligent research is urgently required with high priority. This review
highlights the importance of intelligent research for answers for a new
phenomenon, and demonstrates the necessity for a combination of this approach
with high quality epidemiological research. The reader will notice an emerging
clear picture that the majority (if not all) of these advances have been achieved
from studies funded by independent or charity organizations rather than by the
responsible authorities who are supposed and are duty bound to take on this task.
PMID- 9638281
TI - Status of peer review.
PMID- 9638280
TI - The evolution of human medicines control from a national to an international
perspective.
PMID- 9638282
TI - Emerging infectious diseases: can we meet the challenge?
AB - Demonstration of quality health care includes documentation of outcomes of care.
Surveillance is a comprehensive method of measuring outcomes and related
processes of care, analyzing the data, and providing information to members of
the health care team to assist in improving those outcomes. Surveillance is an
essential component of effective clinical programs designed to reduce the
frequency of adverse events such as infection or injury.
PMID- 9638283
TI - Risk index for prediction of surgical site infection after oncology operations.
AB - INTRODUCTION: Several studies have shown that surgical site infections represent
most hospital-acquired infections, with the major impact being on average
hospital stay and cost of hospitalization. METHODS: To develop a risk model for
prediction of surgical site infections in cancer patients undergoing operative
procedures and identify those with high probability of infection we performed a
prospective cohort study in a tertiary cancer care hospital in Rio de Janeiro,
Brazil. Risk factors were studied in single and multivariate analyses. RESULTS:
Over a 24-month period, 1205 patients underwent operations for malignant disease.
The overall surgical site infection rate was 17.3%. A multivariate stepwise
logistic regression model identified six independent predictive risk factors:
contaminated and infected operations, surgical duration greater than 280 minutes,
male sex, prior radiotherapy, American Society of Anesthesiology class III to V,
and antimicrobial prophylaxis not according to protocol. On the basis of
individual risk scores, two groups of patients were identified: a low-risk (score
< or = 8; surgical site infection rate 10%) and a high-risk group (score > or =
9; surgical site infection rate 33.6%; relative risk 3.4; 95% confidence interval
2.6 to 4.4). CONCLUSION: The oncology risk model allowed for the identification
of a high-risk score group of patients and implementation of a more efficient and
selective intervention program.
PMID- 9638284
TI - Evaluation of infection control parameters according to the 1994 Centers for
Disease Control and Prevention Tuberculosis guidelines: a 2-year experience.
AB - BACKGROUND: Because of classification as a high-risk institution for potential
Mycobacterium tuberculosis exposure and an employee purified protein derivative
conversion rate of 2.7%, a large university-affiliated county hospital enhanced
administrative and engineering controls, as recommended by its tuberculosis task
force in early 1994. METHODS: For 1994 and 1995 the medical records of all
patients with culture-confirmed M. tuberculosis were reviewed according to the
1994 Centers for Disease Control and Prevention guidelines for case surveillance
and risk assessment (infection control parameters). The chi 2-test was used to
compare 1994 and 1995 infection control parameters for statistical significance
(p < or = 0.05). RESULTS: In 1994 and 1995 there were 253 patients with
tuberculosis, 85% of whom (214/253) had pulmonary-site tuberculosis. The
"representative" patient with pulmonary tuberculosis was profiled, along with
institution-specific surveillance data on diagnostics, medication regimens, and
airborne isolation practices. Between 1994 and 1995 there was a trend toward
increased numbers of homeless patients with tuberculosis, from 8.2% to 17% (p =
0.07). Decreases in the numbers of HIV seropositive patients with tuberculosis
from 35% in 1994 to 24% in 1995 (p = 0.2) and of jailed patients with
tuberculosis from 9.8% to 5% (p = 0.5) were not significant. Drug-resistance
patterns increased from 13% to 24%, with borderline significance (p = 0.06). The
employee purified protein derivative testing compliance rate increased from 49%
in 1994 to 74% in 1995, with the purified protein derivative conversion rate also
increasing from 2.7% to 3.5%. CONCLUSION: The infection control parameter data
were beneficial in identification of institution-specific risk factors for our
population with tuberculosis. Although labor-intensive, the annual tuberculosis
reports supported requests for administrative and engineering controls; however,
efficacy of the 1994 tuberculosis control plan was difficult to assess from
purified protein derivative conversion rates alone, because the testing
compliance rate also increased.
PMID- 9638285
TI - An effectiveness and cost analysis of presumptive treatment for Mycobacterium
tuberculosis.
AB - BACKGROUND: Delay in treatment of tuberculosis has contributed to both the spread
of tuberculosis and its case fatality rate. METHODS: Decision analysis was used
to examine the effectiveness and cost of presumptive treatment in patients
evaluated for tuberculosis. RESULTS: Over a range of assumptions, empiric
antituberculous therapy for acid-fast bacillus smear-positive persons lowers
mortality and cost per person evaluated when available rapid diagnostic
laboratory methods for tuberculosis are used. In contrast, the average cost per
life saved by giving presumptive treatment to all acid-fast bacillus smear- and
HIV-negative patients exceeds. $1 million. Empiric treatment for HIV-infected
patients with acid-fast bacillus-negative smears decreases average mortality by
2% at an additional cost of $8000 per life saved. When the prevalence of multiple
drug resistance exceeds 9.6%, presumptive drug-resistant therapy for acid-fast
bacillus smear-positive patients, rather than the initial four-drug regimen
recommended for much of the United States, minimizes both mortality and costs.
CONCLUSIONS: Empiric antituberculous therapy often minimizes average mortality
and cost for patients evaluated for tuberculosis when rapid diagnostic methods
are used.
PMID- 9638286
TI - A survey of infection control professional staffing patterns at University
HealthSystem Consortium institutions.
AB - BACKGROUND: Proper staffing of infection control departments has long been a
topic of interest. The most complete report on the subject, the Study on the
Efficacy of Nosocomial Infection Control, was published in 1985. To provide
current benchmarking comparison data for expected staff reductions at the
University of Michigan Health System, a survey of University HealthSystem
Consortium members was performed. METHODS: A survey tool was developed to obtain
general demographic, staffing, and case-mix information. An infection control
professional at each institution was contacted to obtain most of the information.
Additional information was obtained from standard references. RESULTS: Responses
were obtained from 45 University HealthSystem Consortium members (67%). Full-time
equivalent ratios were based on the following parameters and compared for the
institutions: number of occupied beds (according to occupancy rate, median 137
occupied beds/full-time equivalent), number of intensive care unit beds (median
28 beds/full-time equivalent), number of admissions or discharges (median 6686
admissions/full-time equivalent), number of ambulatory care visits (median
104,426 visits/full-time equivalent), and case-mix index (median 1.75).
CONCLUSIONS: Many institutions are using benchmarking comparison data to make
decisions regarding staff reductions. This survey provides preliminary data for
determining the "best practice" in staffing for infection control departments.
More information may be needed to evaluate other factors that affect infection
control professionals' workload.
PMID- 9638287
TI - Behavioral interventions to improve infection control practices.
AB - No single intervention has been successful in improving and sustaining such
infection control practices as universal precautions and handwashing by health
care professionals. This paper examines several behavioral theories (Health
Belief Model, Theory of Reasoned Action and Theory of Planned Behavior, self
efficacy, and the Transtheoretic Model) and relates them to individual factors,
also considering interpersonal and organizational factors. Further, this article
includes recommendations of individual and organizational components to be
addressed when planning a theoretically based intervention for improving
infection control practices. A hypothetic framework to enhance handwashing
practice is proposed.
PMID- 9638288
TI - Wound infections after hysterectomy: opportunities for practice improvement.
AB - BACKGROUND: This study was designed to determine the frequency of surgical site
infection development after discharge from the hospital after abdominal or
vaginal hysterectomy and the frequency of use of antimicrobial prophylaxis in
this patient group. METHODS: A prospective cohort study was performed on patients
undergoing abdominal or vaginal hysterectomy between February 1 and December 31,
1995. Surgeons were contacted 1 month after the operations to determine which
patients had acquired surgical site infections. Surgical site infection rates
were calculated according to procedure, surgeon, and National Nosocomial
Infection Surveillance system risk categories. A retrospective pharmacy record
review was conducted to determine antimicrobial prophylaxis use according to
procedure and surgeon. RESULTS: A total of 763 cases were surveyed; 55 (7.2%) met
criteria for postoperative surgical site infection (7.7% abdominal and 4.5%
vaginal hysterectomy). National Nosocomial Infection Surveillance system moderate
risk patients had significantly higher infection rates than did low-risk patients
for both abdominal (p = 0.045) and vaginal (p = 0.05) procedures. Most patients
(71.1%) were not given antimicrobial prophylaxis. There was a wide range of
antimicrobial prophylaxis use by surgeon (3.6% to 94.4% of patients, p < 0.01).
CONCLUSION: Despite long-standing and widespread recommendations for
antimicrobial prophylaxis before hysterectomy, most of our patients were operated
on without such prophylaxis. Surveillance programs permit detailed review of
patient care practices that may reveal opportunities for improvement.
PMID- 9638289
TI - Costs of implementing a tuberculosis control plan: a complete education module
that uses a train-the-trainer concept.
AB - BACKGROUND: Tuberculosis once was thought to be nearly eradicated, but there was
a 14% increase in cases of tuberculosis between 1985 and 1993, although decreases
were observed in both 1994 and 1995. To reduce spread of this disease, health
care workers must be familiar with tuberculosis, its signs, symptoms, and modes
of transmission. In October 1994 the Centers for Disease Control and Prevention
issued "Guidelines for Preventing the Transmission of Mycobacterium tuberculosis
in Health Care Facilities." The combination of persistently high tuberculosis
case rates, the development of multidrug-resistant tuberculosis, the new Centers
for Disease Control and Prevention recommendations, and Occupational Safety and
Health Administration enforcement has mandated large-scale training in health
care facilities. METHODS: A tuberculosis control plan was developed and the train
the-trainer concept was selected after review of the hospital's tuberculosis risk
assessment, staff members requiring training, and available teaching staff. The
training program that was developed included tuberculosis pathology and
transmission, national and local epidemiology, placement and evaluation of skin
tests, and an algorithm to assist in determining when isolation is indicated.
RESULTS: One hundred forty-six trainers were trained in 4 days. During the next
quarter, 66% (1989/3000) of staff members requiring instruction were trained. The
total cost involved in development and training was approximately $26,000 and
involved 1600 person-hours. CONCLUSION: Tuberculosis training should be directed
toward high-risk areas, including intensive care units, emergency departments,
and acute medicine wards. Large-scale training is time-consuming and expensive.
Evaluation remains difficult. To facilitate compliance, pretest and posttest
results should be provided, linked to Occupational Safety and Health
Administration compliance and quality indicators for the hospital.
PMID- 9638290
TI - Effect of several interventions on the frequency of handwashing among elementary
public school children.
AB - BACKGROUND: The purpose of this educational project was to assess the effect of
several interventions on the frequency of handwashing among elementary public
school children. METHODS: Participants in this project were first-graders and
fourth-graders from jurisdictions within a mid-Atlantic metropolitan area. Phase
I included a baseline assessment of bathroom cleanliness as well as adequacy of
supplies for handwashing in each school. During phase 2, the frequency of
handwashing before lunch or after bathroom use was monitored and recorded during
a 2-month period. The schools were separated into four groups: a peer education
group, a hand wipes and instructional poster group, a combination of the
education and hand wipes/poster groups, and a (control) comparison school.
RESULTS: Overall, a significant increase occurred in the proportion of
handwashing frequency from preintervention to postintervention for each
intervention group (wipes: 0.50 vs 0.66, p = 0.03; education only: 0.64 vs 0.72,
p = 0.02; and education and wipes: 0.45 vs 0.67, p = 0.03) but not in the control
group (0.42 vs 0.46, p = 0.26). When the first 3 weeks and the last 3 weeks after
intervention were compared, handwashing frequency remained unchanged in the wipes
only group (0.66 vs 0.66, p = 0.96), decreased in the education group (0.77 vs
0.65, p = 0.006), and increased in the education and wipes group (0.58 vs 0.75, p
= 0.003), as well as in the control group (0.37 vs 0.52, p = 0.01). CONCLUSION:
Education combined with accessible convenient hand hygiene may result in a
sustainable increase in the frequency of handwashing among elementary school
children.
PMID- 9638291
TI - Tuberculosis control in New York City hospitals.
AB - OBJECTIVES: To assess the implementation of tuberculosis (TB) control measures in
New York City hospitals in 1992 and determine trends during the subsequent 2
years. METHODS: The 22 acute care facilities with the largest number of
hospitalized TB patients in 1991 were selected for inclusion in the study.
Medical and laboratory records of the 10 most recent acid fast bacilli (AFB)
smear-positive patients in each of the selected facilities in 1992, 1993, and
1994 were reviewed by using a standardized questionnaire to determine risk
factors for TB, previous history of TB, clinical signs and symptoms, AFB
laboratory turnaround times, emergency department contact, timing of isolation,
timing of treatment, case reporting, and status on discharge. The patients' rooms
were evaluated for TB environmental control measures if the patient was still on
respiratory isolation precautions. RESULTS: More than one third of patients were
admitted with a previous history of TB, 31% were admitted with a cavitary lesion
on chest x-ray examination, and 48% were known to have HIV infection. Eighty-five
percent were admitted from the emergency department where they stayed for up to
116 hours (mean stay: 17 hours). The proportion of patients placed in AFB
isolation on admission to the floor increased from 75% in 1992 to 84% in 1994.
The proportion of patients given a minimum of four anti-TB drugs increased from
88% in 1992 to 94% in 1994. Patients "on isolation" were sharing rooms with up to
nine other patients in 1992, whereas no patients were sharing rooms in the 1994
survey. In 1992, 51% of the rooms were under negative air flow with respect to
the corridor. During the 1994 survey, 80% of rooms were under negative air flow.
Between 1992 and 1994, the proportion of AFB isolation rooms with dust/mist
respirators increased from 28% to 76% (p < 0.00001). Approximately 25% of
discharged patients left against medical advice (no trend over time). The
proportion of medically discharged patients with three negative AFB smears before
discharge increased from 26% to 48% (p = 0.03) and the proportion referred for
directly observed therapy increased from 15% to 53% (p = 0.00001). CONCLUSION: TB
control efforts in New York City hospitals improved dramatically between 1992 and
1994. The ultimate control of TB will continue to depend on the coordinated
efforts within and between health care facilities, providers, and the community.
PMID- 9638292
TI - Recommended practices for surveillance. Association for Professionals in
Infection Control and Epidemiology, Inc. Surveillance Initiative working Group.
AB - Demonstration of quality health care includes documentation of outcomes of care.
Surveillance is a comprehensive method of measuring outcomes and related
processes of care, analyzing the data, and providing information to members of
the health care team to assist in improving those outcomes. Surveillance is an
essential component of effective clinical programs designed to reduce the
frequency of adverse events such as infection or injury. Although there is no
single or "right" method of surveillance design or implementation, sound
epidemiologic principles must form the foundation of effective systems and must
be understood by key participants in the surveillance program and supported by
senior management. Teamwork and collaboration across the health care spectrum are
important for the development of surveillance plans. Each health care
organization must tailor its surveillance systems to maximize resources by
focusing on population characteristics, outcome priorities, and organizational
objectives. To ensure quality of surveillance, the following elements must be
incorporated: A written plan should serve as the foundation of any surveillance
program. The plan should outline important objectives and elements of the
surveillance process so that resources can be targeted appropriately.
Thoroughness or intensity of surveillance for an area of interest must be
maintained at the same level over time. Fluctuations of a surveillance rate have
no meaning unless the same level of data collection is maintained. External rate
comparisons are meaningless unless the systems used have comparable intensity.
All the elements of surveillance should be used with consistency over time. This
includes application of surveillance definitions and rate calculation methods.
Personnel resources need to be appropriate for the type of surveillance being
performed. This includes trained professionals who understand epidemiology and
who have access to continuing professional education opportunities. Other
resources essential to surveillance include computer support, information and
technology services, clerical services, and administrative understanding and
support to maintain a quality program. As a means of quality control and to
ensure accuracy, the data and process of surveillance should undergo periodic
evaluation and validation. This document is intended to assist professionals who
plan and conduct surveillance programs as well as those who assure that there is
appropriate organizational support to accomplish appropriate surveillance. While
design of surveillance systems must be unique for each organization,
incorporation of these seven core Recommended Practices for Surveillance provides
a scientific framework to approach surveillance programs.
PMID- 9638293
TI - The microbiology "unknown" misadventure.
AB - A 19-year-old nursing student was hospitalized after several days of nausea,
vomiting, diarrhea, and fevers. Salmonella paratyphi A was isolated from multiple
blood cultures. Because this is an unlikely isolate in the United States, an
investigation ensued. Two and a half weeks earlier, the student had been working
on a microbiology laboratory exercise "unknown." Both the "unknown" organism and
the patient's blood culture isolates were identified as S. paratyphi A, with the
same biochemical reactions and antimicrobial susceptibility results. The
patient's condition improved with antibiotic therapy, and she was discharged
after 9 days in the hospital. Conclusions related to our investigation are as
follows: (1) relatively virulent organisms were unnecessary to fulfill the
laboratory objectives, (2) pipetting by mouth must never be allowed, (3) proper
labeling of specimens is imperative, (4) instructors should have knowledge of
laboratory safety regulations, and (5) it is the obligation of laboratory
directors and administrators to provide a safe academic environment.
PMID- 9638294
TI - Infection surveillance in home care: device-related incidence rates.
AB - BACKGROUND: Four home health agencies of different sizes, including a rural
agency with many branch offices, participated in a surveillance study. METHODS:
These agencies used the same definitions for symptomatic urinary tract infections
in patients with urinary catheters and for bloodstream infections in patients
receiving intravenous therapy. Identical data and methods were used for
calculating infection rates, with device-days consistently used as the
denominator. Each agency's primary goal was to develop baseline information about
its own infection rates and to use these statistics to detect problems and
trends. Chart audits were performed if trends or problems were identified. A
secondary goal was to compare or benchmark infection rates, because there is
almost no published information in this area of home care. RESULTS: We found that
our mean infection rates for symptomatic urinary tract infection among patients
with urinary catheters and for bloodstream infection among patients receiving
intravenous therapy were similar among the four agencies. The mean rates for all
four agencies were 4.5 symptomatic urinary tract infections/1000 device-days and
1.1 bloodstream infections/1000 device-days. CONCLUSION: The methods used here
can be implemented in other home care agencies. Using the same definitions,
collecting data for the same type of infections, and using the same rate
calculations make infection control benchmarking possible between home health
agencies.
PMID- 9638295
TI - Infections in solid organ transplantation.
PMID- 9638296
TI - Testing and evaluation of surgical gown fabrics: comments and concerns.
PMID- 9638297
TI - Leukocytoclastic vasculitis after pneumococcal vaccination.
PMID- 9638298
TI - Benefits of sterile water use in an endoscopic laboratory.
PMID- 9638299
TI - Increasing hospital employee participation in an influenza vaccine program.
PMID- 9638300
TI - Varicella-zoster virus: infection, control, and prevention.
AB - Varicella-zoster virus is a herpes virus that produces a primary infection,
chickenpox, manifested by a vesicular eruption and is considered one of the
common childhood infectious diseases. After the initial infection the virus
becomes latent, then when activated it is manifested as herpes zoster, commonly
known as shingles. This highly communicable human disease is associated with
serious morbidity and significant mortality, particularly among the
immunocompromised. When introduced in the hospital, significant disruptions occur
and serious sequelae may results. Recently, a live virus varicella vaccine was
approved by the Food and Drug Administration in the United States. Studies have
shown the vaccine to be safe and effective. Widespread use of this vaccine may be
beneficial in reducing the opportunities for varicella-zoster virus introductions
in health care settings.
PMID- 9638301
TI - Comparison of native, lyso and hydrogenated soybean phosphatidylcholine as
phospholipid source in the diet of postlarval Penaeus japonicus bate.
AB - Native and two modified forms of soybean phosphatidylcholine were used to study
the nutritional effect of their fatty acids for postlarval Penaeus japonicus.
Five semipurified and isolipidic diets were formulated using casein as a protein
source. Three diets contained 1.5% of different types of phosphatidylcholine (95%
purity), i.e. native soybean phosphatidylcholine, hydrogenated soybean
phosphatidylcholine and 1-acyl lyso soybean phosphatidylcholine, besides 1% of n
3 highly unsaturated fatty acid formulated as triglycerides. Two negative control
diets contained either triglycerides or ethyl esters as a source of n-3 highly
unsaturated fatty acids without phospholipid. The experiment was conducted during
two successive phases of 20 d starting from 12-d old postlarvae. Feeding the diet
containing native soybean phosphatidylcholine resulted in significantly better
growth and resistance to osmotic shock of P. japonicus postlarvae compared to the
other diets. The total lipid content of the tissue was significantly increased by
the supplementation of soybean phosphatidylcholine, whereas no significant
difference was observed for the shrimp fed the modified phosphatidylcholine
sources compared to the phosphatidylcholine-free diet at the end of the
experiment. Shrimp fed the diet containing soybean phosphatidylcholine exhibited
a higher polar lipid fraction in the whole body total lipid mainly as a result of
the increased proportion of phosphatidylcholine and to a lesser extent of
phosphatidylinositol at the expense of free fatty acids, free sterols and sterol
esters. The content of 20:5n-3, 22:6n-3 and total n-3 highly unsaturated fatty
acids in the shrimp tissue were higher in shrimp fed the native soybean and
hydrogenated soybean phosphatidylcholine diets compared to those fed the
phosphatidylcholine-free and 1-acyl lyso soybean phosphatidylcholine-based diets.
The fatty acid profile of tissue phosphatidylethanolamine was more influenced by
the type of dietary phosphatidylcholine than that of tissue phosphatidylcholine.
In the absence of phospholipids in the diet, triglyceride fish oil and a mixture
of ethyl ester concentrate and coconut oil with similar n-3 highly unsaturated
fatty acids content were equivalent sources of n-3 highly unsaturated fatty
acids. The beneficial effects of dietary phospholipids may be due to a more
efficient transport and utilization of dietary neutral lipids through a better
lipid mobilization following absorption in the intestinal mucosa rather than due
to a better emulsification of neutral lipid in the gut lumen. The functionality
of phosphatidylcholine in the diet of postlarval P. japonicus requires the
presence of unsaturated fatty acids and an intact fatty acid moiety.
PMID- 9638302
TI - The effect of porcine bile acids on methane production by rumen contents in
vitro.
AB - Hindgut fermentation differs from rumen fermentation by a lower methane
production and the presence of reductive acetogenesis. Bile acids which are lost
into the lower digestive tract may have a promoting effect on reductive
acetogenesis in the hindgut. In this experiment it was investigated if bile acids
induce reductive acetogenesis in rumen fermentation in vitro. Rumen contents from
a fistulated cow were incubated in vitro with ground hay and increasing amounts
of porcine bile acids or bile acid salts. Bile acids inhibited methane production
up to 70% of the control incubation. The concomitant increase in propionate
production compensated for the lower methane production so that the 2H-recoveries
were in a normal range between 79-92%. Therefore the occurrence of reductive
acetogenesis could be excluded. It is concluded, that bile acids are a
controlling factor in caecal methanogenesis.
PMID- 9638303
TI - Inevitable losses of phosphorus in pigs, estimated from balance data using diets
deficient in phosphorus.
AB - Faecal losses of phosphorus (P) were determined in 66 growing pigs weighing
between 30 and 70 kg on a semi-purified diet containing less than 1.3 g P/kg DM.
Regression analysis showed that the coefficient of absorption of P from this diet
was 82.5% and that inevitable faecal P excretion of pigs fed this diet was, on
average, 5.9 mg/kg BW.d-1 with no statistically significant effect of body weight
on faecal P excretion within the range of body weight studied. Semi-purified
diets almost identical in composition were also fed to 5 piglets weighing about
20 kg and to 4 heavy pigs of about 150 kg BW. Inevitable daily faecal losses of P
were calculated to be 6.2 mg/kg BW in piglets and 6.8 mg/kg BW in the heavy pigs.
It is concluded that inevitable faecal losses of P do depend on body weight and
that the variation faecal P excretion was too great to allow detecting this
effect within the limited range between 30 and 70 kg BW. Further diets were
obtained by blending various ingredients into the semi-purified diet. From a
total of 262 balances measured under the condition of suboptimal P supply it is
concluded that daily inevitable urinary losses of P depend on body weight and, on
average, amount to 0.35 mg/kg BW. It is concluded that under the conditions of
suboptimal P supply the utilisation of digestible P is almost complete.
PMID- 9638304
TI - [Effect of various sources of phosphorus on the apparent digestibility of crude
nutrients, growing and slaughtering performance as well as selected parameters of
metabolism in fattening bulls].
AB - Two long-term individual feeding experiments (336 and 307 days) were carried out
with 52 (experiment I; Black and White dairy cattle) and 22 (experiment II;
Yellow cattle) growing bulls. Rations varied in P-content. In experiment I straw:
concentrate-mixture (1:2.5) were fed, phosphorus content of rations amounted to
2, 3 or 4 g/kg DM. In experiment II maize silage was fed ad lib. supplemented
with 2.4 kg concentrate per animal per day. P-content of rations amounted to 3
and 4 g/kg DM. Apparent digestibility of rations was determined during
experiments. Blood samples were taken to analyse selected parameters of
metabolism. Various P-supply did not significantly influence apparent
digestibility of organic matter and crude nutrients in both experiments. Bulls
fed 2 g P/kg DM decreased DMI in experiment I already after 50 days of
experiment. After 168 experimental days daily weight gain of bulls fed with 2 g
P/kg DM was 124 or 132 g lower than that of bulls fed with 3 or 4 g P/kg DM
respectively. P-concentration of inorganic P in serum decreased to < 2 mmol/l,
bone mineralisation was reduced. There exist no significant differences in feed
intake, weight gain and metabolic parameters of bulls fed with 3 or 4 g P/kg DM.
Increase of P-supply from 2 to 3 or 4 g/kg DM compensated partially the lower
weight gain. Application of 3 or 4 g P/kg DM in experiment II effected daily
weight gains of > 1200 g and did not significantly influence all investigated
criterions.
PMID- 9638305
TI - Effect of different technical treatments of rapeseed on the feed value for
broilers and laying hens.
AB - The effect of different technical treatments of rapeseed on its feed value for
broilers and laying hens was the object of the study. The technical treatments
comprised different grinding procedures (whole seed, roller mill--coarse and fine
adjustment, flake mill) resulting in different average particle sizes of the
ground seed and thermal treatments of flaked seed (hydrothermal treatment,
micronizer, jet sploder). Each thermal treatment was carried out at two
temperatures. A marked increase in the digestibility of organic matter and of the
AMEN content was observed as the average particle size of the seed was decreased
to < or = 0.56 mm and was much more pronounced for the broilers. AMEN contents of
21.1 to 22 and 22.6 to 23 MJ/kg DM were observed at this particle sizes for
broilers and hens, respectively. Thermal treatment of rapeseed improved the
apparent crude fat digestibility slightly whereas the apparent crude protein
digestibility tended to decrease especially at the higher temperatures. This
resulted in inconsistent changes in the apparent digestibility of the organic
matter and the AMEN content. Only the treatment with hot air (jet sploder) seemed
to have preferential effects on the feed value for both broilers and hens. For
the thermal treatments AMEN contents ranged from 18.8 to 21.9 and 19.0 to 24.3
MJ/Kg DM for broilers and hens, respectively.
PMID- 9638306
TI - The effect of sealing and of additives on the fermentation characteristics and
mould and yeast counts in stretch film wrapped big-bale lucerne silage.
AB - The effect of number of film layers was investigated in silages produced in
wrapped big bales. The herbage used was difficult to ensile lucerne wilted to DM
levels of 320-490 g/kg. Fermentation changed to a more homofermentative process
as the number of film layers increased. An increasing number of film layers (4,
6, 8 or 10) also resulted in a notable decrease in moulds and yeasts. Four layers
could not guarantee successful preservation in lucerne, and higher numbers of
undesirable micro-organisms were detected. Hard stalks damaged the first two film
layers during wrapping in the bales. Effect of number of film layers was more
important than effect of additives for inhibition of mould and yeast counts.
PMID- 9638307
TI - Research note: a comparison of metabolisable energy values of lucerne and barley
between young and mature ostriches.
AB - Apparent and true metabolisable energy (ME) values, corrected for zero nitrogen
retention, of lucerne and barley were compared in balance studies between young
(six months old, 50 to 60 kg BW) and mature (30 months old, 110 to 120 kg BW)
ostriches. Birds were housed in individual metabolism crates and excreta
collection were performed over a five day period after an adaptation period of
seven days. Apparent metabolisable energy, corrected for zero nitrogen retention,
(AMEN) of 9.17 +/- 0.251 MJ/kg (lucerne) and 14.24 +/- 0.136 MJ/kg (barley) for
young ostriches do not differ (P > 0.05) from values of 8.97 +/- 0.226 MJ/kg
(lucerne) and 14.21 +/- 0.134 MJ/kg (barley) obtained for mature ostriches. Also
no significant differences occurred between true metabolisable energy, corrected
for zero nitrogen retention, (TMEN) values of 9.16 +/- 0.450 MJ/kg (lucerne) and
13.94 +/- 0.390 MJ/kg (barley) for young ostriches and 9.26 +/- 0.412 MJ/kg
(lucerne) and 13.92 +/- 0.316 MJ/kg (barley) for mature ostriches. It is
concluded that similar AMEN and TMEN values of feedstuffs would be suitable in
ostrich diet formulation for age groups older than six months.
PMID- 9638308
TI - Metabolism of 2(R,S)-1,2-bis(nicotinamido)propane, a new agent with anti
vasospasm activity, in rats and rabbits.
AB - 1. The metabolic fate of the new Anti-vasospasm Substance (AVS), 2(R,S)-1,2
bis(nicotinamido)propane (CAS 79455-30-4), was studied using 14C-labelled drug in
rats and rabbits by thinlayer chromatography, mass spectrometry and nuclear
magnetic resonance. 2. More than 75% of the radioactivity was observed in the
urine when 14C-AVS was given intravenously to rabbits and rats, showing that the
major route of excretion of AVS and its metabolites is via the kidney. 3. Marked
species differences were observed in the metabolism of AVS in rats and rabbits.
In rabbits, the major metabolites were 6- or 6'-monopyridone (23.5% of dose), and
there were a few minor metabolites such as the mono N- or N1-oxide of two
pyridine rings. In rats, however, only approximately 5% of the radioactivity was
due to metabolites, mainly the N-oxide. 4. Formation of AVS monopyridone by
rabbit liver cytosol was much higher than in rats, and was markedly inhibited by
the aldehyde oxidase inhibitor, menadione. The difference between rats and
rabbits in oxidase activity giving the AVS monopyridone metabolite correlated
well with that measured by the general assay method for aldehyde oxidase. These
results suggest that the species difference in AVS metabolism between rats and
rabbits is mainly due to the difference in aldehyde oxidase activity, which is
involved in formation of the monopyridone.
PMID- 9638309
TI - Pharmacokinetics of tramadol and bioavailability of enteral tramadol
formulations. 2nd communication: drops with ethanol.
AB - The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride
(CAS 36282-47-0) after oral administration of Tramal drops (with ethanol) were
determined in a balanced cross-over study in 8 (4 male and 4 female) volunteers
in comparison with the intravenous injection. Each fasting volunteer received two
single doses of 100 mg tramadol-HCl, one by oral (1 ml of drops) and one by
intravenous route (2 ml of a solution for injection). The formulations were
administered in the morning; the washout period was one week. Serum and urine
concentrations of tramadol-HCl were determined by gas chromatography-mass
spectrometry and gas chromatography, respectively, and the pharmacokinetic
evaluation was carried out model-dependently. Only the extent of bioavailability
and the renal clearance were calculated model-independently. The extent of the
absolute bioavailability (F) of tramadol after oral administration of the drops,
based on AUC data, was 66.3% (point estimate; n = 8) with a 95% confidence
interval of 58.1-75.6% (ANOVAlog). The areas under the serum concentration curves
of tramadol-HCl calculated by curve fitting (AUC), which agreed very well with
the model-independently determined areas (AUC), were 2390 +/- 712 h.ng/ml (p.o.)
and 3490 +/- 510 h.ng/ml (i.v.) (mean +/- SD; n = 8). After oral administration
the means of the serum concentration peaks were 308 +/- 89 ng/ml (cmax) and 1.20
+/- 0.39 h (tmax), the half-life of absorption was 0.34 +/- 0.18 h (t1/2,ka) and
the lag time 0.23 +/- 0.01 h (t0). The biological half-life in the terminal phase
(t1/2,beta) was 5.5 +/- 0.9 h and agreed well with the value of 5.2 +/- 0.8 h
determined after i.v. injection. There were large differences between the
volunteers in the distribution rate. For the slower distribution half-life
(t1/2,alpha) mean values of 1.2 +/- 0.7 h (p.o.; n = 6) and 1.9 +/- 0.7 h (i.v.;
n = 6) were obtained. The values determined after i.v. injection for the total
distribution volume and the total and renal clearance were 216 +/- 21 l
(Vd,beta), 487 +/- 71 ml/min (Cltot) and 77 +/- 20 ml/min (Clren), respectively.
These results show that after administration of the drops (with ethanol) the
active ingredient tramadol is rapidly absorbed and that the extent of the
absolute bioavailability is about the same as after oral administration of
tramadol capsules.
PMID- 9638310
TI - Disposition of the novel anti-schizophrenic drug [14C]olanzapine in male Fischer
344 and female CD rats following single oral dose administration.
AB - These studies comprehensively evaluate the distribution of [14C]olanzapine (2
methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)-1,5)benzodiazepin e, CAS
132539-06-1, LY170053) a novel anti-schizophrenic compound, following single oral
dose administration in male Fischer 344 rats, and pregnant and non-pregnant
lactating female CD rats. The disposition of radiocarbon was determined and
tissue pharmacokinetics evaluated in male Fischer 344 rats following a single
oral 8 mg/kg dose at 2, 6, 24, 48, 72, and 96 h postdose using quantitative whole
body autoradiographic (QWBA) techniques in conjunction with image analysis. This
study demonstrated that [14C]olanzapine and/or metabolites were rapidly absorbed
and widely distributed with a tmax of 2 h postdose in most tissues. Persistent
but declining concentrations of radiocarbon were detected in feces, kidney,
liver, and Harderian, preputial, and thyroid glands at 96 h postdose. Placental
transfer of [14C]olanzapine was evaluated at 0.5, 1, 3, 6, and 24 h postdose on
gestation day 12, the mid-point of organogenesis, by tissue dissection and liquid
scintillation spectroscopy (LSC) and on gestation day 18, a time which enabled
visualization of fetal tissues by whole-body autoradiography (WBA). The placental
transfer studies indicated that all tissues analyzed had a tmax of 1 or 3 h
postdose with maternal liver consistently containing high concentrations of
radiocarbon. Embryos contained measurable concentrations of radiocarbon
throughout the time course of these studies confirming that [14C]olanzapine
and/or its metabolites crossed the placenta. Additionally, the disposition of
[14C]olanzapine in milk and plasma of lactating female CD rats confirmed pup
exposure through milk ingestion.
PMID- 9638311
TI - Absorption of the new anxiolytic compound deramciclane in rats, dogs and rabbits.
AB - The absorption of deramciclane fumarate ((1R,2S,4R)-(-)-N,N-dimethyl-2-[(1,7,7
trimethyl-2-phenylbicyclo [2,2,1] hept-2-yl) oxy] ethane amine-2-(E)-butenedioate
(1:1), CAS 120444-78-8, EGIS-3886), a new anxiolytic compound, was studied in
rats, dogs and rabbits by using 3H-camphor- or 14C-phenyl-labelled radioisomers
of the substance. The compound was readily absorbed from the intestinal tract
after oral administration. The absorption of 14C-deramciclane was also studied
from the isolated intestinal loops of rats (duodenal, jejunal, ileal loops) and
dogs (duodenal loop). The absorption was faster in rats and rabbits than in dogs
(tmax = 1 h or 6 h, respectively). The radioactivity was not absorbed from the
isolated stomach of any species studied for 2 h. Meanwhile, the substance was not
decomposed by the gastric juice, as it has been proved by TLC and MS analyses.
Deramciclane is preferentially excreted via the bile. The intensity of its bile
excretion is higher in rats than in dogs. Higher plasma levels of labelled
deramciclane were found in female than in male rats.
PMID- 9638312
TI - Comparative autoradiographic investigations on the tissue distribution of
benfotiamine versus thiamine in mice.
AB - The tissue distribution of two therapeutically applied preparations of B-vitamins
were investigated in blood and selected organs (liver, brain, muscle, kidney) of
laboratory mice using autoradiographic techniques. Incorporation of lipid-soluble
3H-benfotiamine (CAS 22457-89-2) and water-soluble 3H-thiaminehydrochloride (CAS
67-03-8) (200 microCi, equivalent to 105 mg vitamin/kg body weight) was monitored
between 0.75 and 168 h after an oral or subcutaneous administration. The labelled
tissue slices were autoradiographically analysed after a differential
histochemical extraction procedure to evaluate the respective total
radioactivity, the uptake into lipid-soluble, water-soluble and residual
macromolecular compounds. Evaluation of these autoradiographic data (given as
mumol vitamin preparation/mg tissue equivalent) proved that benfotiamine is
incorporated much better than thiaminehydrochloride independent of the
administration mode. In muscle and brain tissue a 5 to 25 fold higher amount of
tracer incorporation was registered following benfotiamine as compared with the
thiamine application, whereas in all other organs the difference in the label was
mostly between 10 and 40%. Concerning the organ specific distribution, liver and
kidney were the structures labelled highest by both substances and administration
procedures. In the liver, concerning all incorporation times, a higher proportion
of residual macromolecular compounds was found, whereas in the kidney the
proportions of lipid- as well as of water-soluble materials prevailed. These data
should be clinically relevant.
PMID- 9638313
TI - Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee
osteoarthritis.
AB - A double-blind therapeutic investigation was performed on 178 Chinese patients
suffering from osteoarthritis of the knee randomized into two groups, one treated
for 4 weeks with glucosamine sulfate (GS, CAS 29031-19-4, Viartril-S) at the
daily dose of 1,500 mg and the other with ibuprofen (IBU, CAS 15687-27-1) at the
daily dose of 1,200 mg. Knee pain at rest, at movement and at pressure, knee
swelling, improvement and therapeutic utility as well as adverse events and drop
outs were recorded after 2 and 4 weeks of treatment. The variables were recorded
also after 2 weeks of treatment discontinuation in order to appreciate the
remnant therapeutic effect. Both GS and IBU significantly reduced the symptoms of
osteoarthritis with the trend of GS to be more effective. After 2 weeks of drug
discontinuation there was a remnant therapeutic effect in both groups, with the
trend to be more pronounced in the GS group. GS was significantly better
tolerated than IBU, as shown by the adverse drug reactions (6% in the patients of
the GS group and 16% in the IBU group--p = 0.02) and by the drug-related drop
outs (0% of the patients in the GS group and 10% in the IBU group--p = 0.0017).
The better tolerability of GS is explained by its mode of action, because GS
specifically curbs the pathogenic mechanisms of osteoarthritis and does not
inhibit the cyclo-oxygenases as the non-steroidal anti-inflammatory drugs
(NSAIDs) do, with the consequent anti-inflammatory analgesic activities but also
with the several adverse reactions due to this not targeted effect. The present
study confirms that GS is a selective drug for osteoarthritis, as effective on
the symptoms of the disease as NSAIDs but significantly better tolerated. For
these properties GS seems particularly indicated in the long-term treatments
needed in osteoarthritis.
PMID- 9638314
TI - Synergistic effects of ularitide acetate with classical bronchorelaxants on
guinea-pig tracheal smooth muscle.
AB - Ularitide (CAS 118812-69-4, urodilatin) is a member of the family of the atrial
natriuretic peptides. In the present study, the relaxant effects of ularitide
acetate, isoproterenol (isoprenaline) hemisulfate, aminophylline, zaprinast, and
different combinations between these drugs were investigated on methacholine
chloride-precontracted guinea-pig tracheal smooth muscle. Ularitide acetate was a
weaker bronchorelaxant than isoproterenol hemisulfate and aminophylline. Moreover
the relaxation induced by ularitide acetate was reversible, while the relaxation
induced by isoproterenol hemisulfate, aminophylline, and zaprinast was
irreversible. Combinations between in each case two of these substances were
overadditive, if the phosphodiesterase-inhibiting component was applicated before
the combination partner. Their effects were only additive, if the combination
partners were applicated simultaneously. All combinations between ularitide
acetate and isoproterenol hemisulfate, aminophylline, or zaprinast respectively
relaxed the tracheas irreversibly. These results suggest that ularitide acetate
might be a novel partner for classical bronchorelaxants in potent bronchorelaxing
combinations in the therapy of asthma bronchiale.
PMID- 9638315
TI - [The action of the proton pump inhibitor pantoprazol against acetylsalicylic acid
induced gastroduodenopathy in comparison to ranitidine. An endoscopic controlled,
double blind comparison].
AB - In a randomised double-blind parallel study the gastroduodenal tolerability of
300 mg acetylsalicilic acid daily (ASA, CAS 50-78-2) has been evaluated in the
presence of placebo (n = 8), 40 mg pantoprazole (CAS 102625-70-7) daily (8 a.m.)
(n = 16) and 300 mg ranitidine (CAS 66357-35-5) daily (8 a.m.) (n = 16) in
healthy volunteers using upper GI-endoscopy. The treatment period lasted 14 days,
endoscopic controls were performed at entry and repeated at day 14. At entry, the
mean endoscopic score averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo, in the
ASA/pantoprazole and the ASA/ranitidine group. In the placebo experiments 300 mg
ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 6.8 +/
1.4 (+/- SEM). Concomitant administration of 40 mg pantoprazole daily offered
significant protection against 300 mg ASS daily on day 14 (2.1 +/- 0.6) (+/- SEM)
(p < 0.05) vs ASA/placebo. 300 mg ASA plus 300 mg ranitidine daily reduced the
damaging score to 4.9 +/- 1.2 (+/- SEM) (n.s. vs ASA/ placebo). Our data suggest
that coadministration of 40 mg pantoprazole daily reduces significantly
gastroduodenal lesions evoked by 300 mg ASA daily.
PMID- 9638316
TI - [Intravesical instillation of trospium chloride, oxybutynin and verapamil for
relaxation of the bladder detrusor muscle. A placebo controlled, randomized
clinical test].
AB - Therapy of detrusor hyperactivity with anticholinergic agents often is followed
by adverse drug reactions. Intravesical application may be an interesting
alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical
trial was carried out in 84 patients with urgency or urge incontinence. Due to
intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium
chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in
maximum bladder capacity and decrease of detrusor pressure accompanied by an
increase of residual urine were found in comparison to placebo in urodynamical
investigations. Improvement of uninhibited bladder contractions occurred leading
to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked
changes in the efficacy variables were found compared with placebo. All patients
completed the study and were assessed with regard to efficacy and safety. No
adverse events or marked changes in the vital signs were reported. The immediate
onset of effect and the lack of adverse drug reactions suggest that treatment
with topical oxybutynin or trospium chloride is an effective alternative in
patients with intolerable side effects when orally treated. In addition,
intravesical administration may be indicated in patients with bladder spasms due
to indwelling catheter or in order to increase bladder capacity before
percutaneous cystostomy.
PMID- 9638317
TI - In vitro studies on the influence of carbomers on the availability and
acceptability of estradiol gels.
AB - The objective of the present study was to evaluate the pharmaceutical properties
of estradiol (CAS 50-28-2) gels: pH, viscosity, texture, spreadability,
evaporation of solvent and transcutaneous diffusion from carbomer-based
formulations. This study was performed with the aim of measuring possible
pharmaceutical differences as a function of the nature of the polymers used. The
results obtained show a similarity of behaviour for the Estreva gels made with
carbomers Carbopol 1342 (C 1342) and 1382 (C 1382). The reference gel,
commercially available in France and made with the carbomer Carbopol 934 (C 934)
is different in terms of its rheological criteria.
PMID- 9638318
TI - Effects of a standardized mistletoe preparation on metastatic B16 melanoma
colonization in murine lungs.
AB - The immune response-modifying drug Lektinol is a mistletoe preparation which is
standardized with respect to bioactive viscum album agglutinin, the most active
component of mistletoe. The present study was designed to evaluate the
antimetastatic effects of this preparation following intravenous injection of B16
melanoma cells into mice. The standardized mistletoe extract was administered
intravenously in doses of 100, 1000 or 5000 microliters/kg (equivalent to 3, 30
or 150 ng/kg of viscum album agglutinin) once daily for three weeks. An
inhibition of mean pulmonary metastatic colonization of 58 to 95%, as measured by
the number of melanoma cells on lung tissue slides, and a significant decrease of
percentage of bronchoalveolar lavage pigmented cells were observed. In addition,
a correlation of this antimetastatic activity with cellular immune parameters was
investigated. In lavage fluids from the tumor-bearing mice, there was a 5 to 6
fold significant increase in the percentage of MAC-1+ (CD11b/CD18)
immunocompetent macrophages in comparison with cells from vehicle-treated
animals. The percentages of double-positive immature CD4+8+ thymocytes were
significantly increased in animals treated with the standardized mistletoe
extract. There were no signs of treatment-related toxicity. The results of this
study indicate that the standardized mistletoe extract shows antimetastatic
activity against B16 melanoma lung colonization.
PMID- 9638319
TI - [Quality control and documentation of effectiveness of bacterial autovaccines
with the use of flow cytometry].
AB - Autovaccines are bacterial preparations derived from non pathogenic autologous
bacteria of human origin. In the course of microbiological therapy these
individual bacterial vaccines are mainly used in conditions of chronic
inflammatory disorders of the respiratory or gastrointestinal tract as well as
allergic diseases. Being autologous bacterial preparations from the patients own
flora the control of batch variabilities of these individual products represents
a special challenge for the manufacturer. A flow cytometric method suitable for
batch control of autovaccines is described. The method is based upon the
determination of the de novo expression of the CD69 antigen on different
leucocyte subpopulations in whole blood cultures after preincubation of cells
with different batches of autovaccines. Thus, manufacturers of autovaccines and
other microbial preparations are able to reliably control batch variability and
immunological activity of such products in accordance with drug regulations. The
results of this study highlight the pharmaceutical quality of the individual
therapeutic agent autovaccine.
PMID- 9638320
TI - Absorption and excretion of radioactivity after intravaginal administration of an
advanced delivery system of 14C-flutrimazole vaginal cream to postmenopausal
women.
AB - In order to improve the effectiveness of treatment of vaginal yeast infections,
flutrimazole, (CAS 119006-77-8), a broad spectrum local imidazolic fungicide, has
been formulated in an advanced delivery system (Site Release, here in after
briefly referred to as SR) designed to improve vaginal retention of the drug. To
determine the extent of absorption of 14C-flutrimazole from this formulation, the
absorption and excretion of total radioactivity have been studied in healthy
postmenopausal female volunteers after intravaginal administration of
approximately 5 g of SR Vaginal Cream containing 2% 14C-flutrimazole.
Concentrations of unchanged flutrimazole have also been measured in plasma and
urine, using a validated gas chromatography-mass spectrometry method. The rate of
absorption was slow, with a mean peak plasma radioactivity concentration, Cmax,
of 56 ng equivalents/ml, achieved at a mean Tmax of 28 h. Corresponding
parameters for flutrimazole were 1.94 ng/ml at 24 h. At 24 h post-dose, unchanged
flutrimazole represented only 3% of plasma total radioactivity which indicates
that flutrimazole is extensively metabolised in man. Total radioactivity and
unchanged flutrimazole were eliminated from plasma with terminal half-lives of 37
and 22 h, respectively. From the proportion of the radioactive dose excreted in
urine and faeces, the maximal extent of absorption indicated for the intravaginal
dose was about 8%, which is similar to that observed with other imidazolic
compounds administered by this route. Thus, the formulation achieves the aim of
prolonged drug action through the maintenance of therapeutic concentrations of
the drug at the site of infection without notably increased absorption.
PMID- 9638321
TI - Identification and development of new biopharmaceuticals.
AB - The 34 protein based biopharmaceuticals which are presently on the market reached
a total sale of 10 Mio $ in 1996. Out of 500 biopharmaceutical under
investigation, 200 are already in clinical trial programs. Although
biopharmaceuticals have good records in efficacy and drug safety, biologics are
still competitive due to economic reasons. In future in some cases gene therapy
or oligonucleotide antisense therapy as modern technologies for in vivo protein
synthesis regulation will be an alternative to protein replacement therapy. All
three therapeutic approaches will be supported by the human genome project which
will give new hints on genetic disorders related to specific diseases. The
identification of new therapeutic developments will be on the DNA-, RNA- and
protein level. The decision whether the therapeutic principle will be gene
therapy or whether the differential genomic analysis will provide just a research
tool for high through-put screening of small molecules will be decided upon the
evaluation of the results of the genomic projects and the research strategy of
the company.
PMID- 9638322
TI - Recovery and rehabilitation following subarachnoid haemorrhage. Part I: Outcome
after inpatient rehabilitation.
AB - BACKGROUND AND PURPOSE: Although subarachnoid haemorrhage (SAH) is a subtype of
stroke, functional outcome following rehabilitation for SAH must be considered
distinct from that of cerebral infarction because of the younger age and the
difference in pathology and resultant neurologic deficits. The purposes of this
study were to: (1) describe the demographic and clinical characteristics of SAH
patients receiving rehabilitation; (2) describe functional outcomes following
inpatient rehabilitation; and (3) investigate possible relationships between
patient characteristics and functional outcomes. METHODS: Retrospective chart
review of SAH patients admitted to inpatient rehabilitation. Functional Outcomes
rated by the Functional Independence Measures (FIM). Analysis with descriptive
and nonparametric statistics. RESULTS: Eighty patients with SAH admitted to a
rehabilitation unit with a mean age of 54 years. Fifty-seven had identified
aneurysms as a cause of SAH. Seventy-four subjects (93%) presented with Hunt and
Hess grades of 3-5. The median length of stay was 26 days in acute care and 49
days in rehabilitation. Seventy patients (88%) were discharged home. The mean
admission FIM was 59.5 and mean discharge FIM 91.0. The FIM efficiency (aggregate
change in FIM/day) was 0.62/day and the average rate of FIM gain 0.97 points/day.
Hydrocephalus negatively influenced outcome (p = 0.05). There was a trend for
subjects with worse Hunt and Hess scores at onset to have poorer discharge FIM
scores. CONCLUSION: SAH patients receiving inpatient rehabilitation make
functional gains, although the rate of gain is less than for TBI or stroke. These
SAH patients represent a subgroup with more severe SAH at onset than the total
population of SAH survivors. The presence of hydrocephalus negatively impacts on
outcome. Further detailed study of functional and neuropsychological outcome in
SAH survivors is needed.
PMID- 9638323
TI - Incidence and outcomes of traumatic brain injury and substance abuse in a New
Zealand prison population.
AB - The present study investigated the rates and perceived effects of past traumatic
brain injury (TBI) and substance use in a prison population. Responses to a
questionnaire indicated that 86.4% of the 118 respondents had sustained a TBI,
with 56.7% reporting more than one, and rates of illicit substance use were
higher than the general population. Maori reported 12% more TBI and more
substance use than non-Maori. All those with TBI reported difficulties with
general memory and socialization on a problem rating scale, but there was no
relationship between level of difficulty and severity of TBI, problems with
interpersonal relationships, family, and finances were associated with greater
substance use.
PMID- 9638324
TI - Caring for a family member with a traumatic brain injury.
AB - The responses to a questionnaire on subjective burden are reported for 52 primary
caregivers of a group of persons with traumatic brain injuries sustained an
average of 6 years previously. The aim of the study was to examine satisfaction
with social support, perception of coping skills, and appraisal of symptoms as
predictors of strain in the carers. A range of responses, both positive and
negative, to the work of caring for a relative with a head injury was reported. A
high prevalence rate of emotional and behavioural changes in the persons with
head injuries was found and the amount of distress caused by these symptoms was
found to be predictive of burden. The other factor important in predicting burden
was the carers' ratings of their satisfaction with their ability to cope with the
work of caregiving. Social support, injury severity, and the demographic
characteristics of the persons with head injury and their carers were not
significant predictors. Depression in the carers was also investigated and the
variable most predictive of elevated depression scores was coping satisfaction.
These findings reinforce the importance of strengthening carers coping resources
in rehabilitation work with head injured persons and their families.
PMID- 9638325
TI - Primary caregivers of persons with brain injury: life change 1 year after injury.
AB - The impact of a traumatic brain injury on the family of the injured person is
just beginning to be explored. In the current study, 61 primary caregivers were
contacted at 1 year following injury. They completed the Relative and Friend
Support Index, Social Support Index, Trauma Complaints List and the Life Change
Question. The majority of caregivers indicated at least mild negative life change
following the brain injury. Greater social support was correlated with less life
change and greater injury severity was correlated with negative life change.
Neither of these relationships was found to be significant at the 0.05 level. A
significant positive correlation was found between caregivers' perception of
deficits and the degree of negative life change. Perceived deficits accounted for
the greatest amount of variance in life change followed by relative and friend
support when all variables were entered into a stepwise regression. Further
analyses indicated that the most significant factor of the Trauma Complaints List
in predicting life change may be problems with cognition, which accounted for a
significant amount of the variance in life change. Implications for counselling
and further research regarding caregivers of persons with brain injury are
discussed.
PMID- 9638326
TI - The ability to effect intended stress following traumatic brain injury.
AB - This study was designed to explore the production of word stress following
traumatic brain injury (TBI). Ten subjects with TBI and ten matched normal
controls produced a sentence with stress elicited on different words. The
difference between stressed and unstressed productions of the same word was
calculated for intensity, fundamental frequency and duration. Subject's intensity
range, fundamental frequency range and vital capacity were also obtained. Naive
listeners judged which word was stressed within each sentence. Individuals with
TBI were significantly less accurate conveying intended stress compared with
normal controls. Individuals with TBI produced significantly less difference in
duration between stressed and unstressed words. There was no correlation for
either group between percentage change in intensity, fundamental frequency, or
duration and the related physiological range. Durational control requires subtle
physiological adjustments that individuals with TBI may be unable to accomplish.
Further, compensatory strategies may place excessive cognitive demands on the
speaker. Thus, the production of stress contrasts may not be amenable to
therapeutic intervention. Rather, listeners may be required to rely on context to
infer intended stress.
PMID- 9638327
TI - Are the subjective complaints of traumatically brain injured patients reliable?
AB - The present study was designed to compare the subjective complaints of 50
traumatically brain injured (TBI) patients with the observations of their
significant others. The complaints of the TBI patients and their significant
others were contrasted according to the severity of the TBI and the type of
complaint (physical, cognitive/behavioural and emotional). While no differences
were found in physical complaints, the cognitive/behavioural and emotional
complaints of TBI patients, regardless of the severity of the initial TBI, were
significantly under-reported in comparison to the observations of their
significant others. The data suggests that while this finding was most likely due
to the TBI patients' poor awareness, it was unlikely to be the result of
psychological denial since all of these individuals were evaluated in the context
of being a plaintiff in personal injury litigation or a claimant in a Workers'
Compensation claim. The data suggests that the cerebral trauma these patients
sustained played a major role in their ability to recognize their cognitive,
behavioural and emotional symptoms. Finally, the data suggests that clinicians
should obtain information about the TBI patients' cognitive/behavioural and
emotional functioning from their significant others, rather than rely entirely on
the TBI patients' subjective assessment of these problems.
PMID- 9638328
TI - Assessment of neuroendocrine dysfunction following traumatic brain injury.
AB - Posttraumatic neuroendocrine pathology may be a clinically significant
complication following traumatic brain injury (TBI). Metabolic abnormalities are
described after TBI in two cases. A 21 year old male injured in a motor vehicle
accident admitted in a minimally responsive condition presented with fluctuating
high sodium levels, undetectable serum testosterone, and depressed cortisol and
thyroid function. Imaging revealed near complete avulsion of the pituitary stalk
leading to panhypopituitarism. A 38 year old male admitted for occipital skull
fractures and brain contusions presented with hyponatremia and low serum
testosterone. Both patients required hormonal replacement and correction of
electrolyte abnormalities. A screening protocol adapted for selected patients at
risk for endocrine problems is described. While neuroendocrine screening is not
advocated in all TBI patients, physicians should be aware of the importance of
neuroendocrine dysfunction following TBI.
PMID- 9638329
TI - Increase in the chronically monitored cerebrospinal fluid pressure after
experimental brain injury in rats.
AB - The early effects of experimental brain injury with diffuse axonal lesions on
intracranial pressure (i.c.p.), mean arterial pressure (MAP) and cerebral
perfusion pressure (CPP) in rats have been already studied. The aim of this
experiment was to examine the effects of brain injury on ICP, MAP and CPP during
the first few days post-injury. In order to do that, an accurate technique of ICP
measurement had to be developed. In a series of eight rats, a translumbar
intrathecal catheter (TIC) was surgically introduced allowing repeated
measurements of cerebrospinal fluid pressure (CSFP). Under anaesthesia, a second
series of nine rats were equipped simultaneously with TIC and an intracranial
fiberoptic device to measure ICP. Simultaneous measurements of CSFP and ICP were
recorded for baseline values, than during and after jugular compression which was
intended to induce an acute and significant increase in ICP. A third series of 53
rats having TIC received an experimental severe brain injury. MAP was measured
non-invasively and CPP was calculated as CPP-MAP. CSFP, MAP and CPP were
intermittently measured during 5-6 post-traumatic days and compared to the values
obtained during ten control rats (SHAM). A clinical score was used to compare
clinical condition. The results showed that the translumbar CSFP accurately
measured ICP in rats having normal or acutely increased ICP. The experimental
brain injury induced increased CSFP lasting up to 5-6 days, with increased MAP
during the first 6 hours. CPP values were compromised at 24-48 hours. The
clinical performance was reduced in the brain-injured rats. The translumbar
technique of CSFP measurement reflected exact ICP in normal and acutely increased
ICP in rats. Experimental brain injury with diffuse axonal lesions can increase
lumbar CSFP in rats for many days.
PMID- 9638330
TI - Adhesion and cytosolic dye transfer between macrophages and intestinal epithelial
cells.
AB - Activated macrophages (M phi) found in the intestinal lesions of patients with
inflammatory bowel disease (IBD) secrete many inflammatory mediators which can
regulate intestinal epithelial cell (IEC) function. However, little is known
about direct M phi-IEC interactions. Two potential mechanisms by which cells may
interact are through specific receptor-ligand binding of adhesion molecules, such
as integrins or cadherins, and by exchange of cytoplasmic substances through
transmembraneous channels called gap junctions. We investigated whether M phi
could adhere to epithelial cells in culture and form transmembrane communication
channels as defined by dye transfer. Primary cultures of murine M phi and a M phi
cell line, P388D1, adhered to Mode-K and IEC6, but not CMT-93 IEC. Antibody
blocking studies determined that P388D1-Mode-K binding was partially dependent on
beta 2 integrin (CD18) function, Mode-K constitutively expressed CD106 (VCAM-1)
and cell associated fibronectin, while P388D1 expressed low levels of CD49d/CD29
(VLA4) but blocking antibodies to these surface molecules did not inhibit P388D1
Mode-K adherence. Transfer of calcein dye from M phi to IEC was quantitated by
flow cytometry and was dependent on M phi-IEC adhesion. Dye transfer was
concentration dependent in that the fluorescence intensity of Mode-K was
proportional to the number of adherent P388D1 cells as well as the dye load of
the M phi. These results indicate that M phi interact with IEC by adhesion and
possibly through gap junctions and may thus regulate IEC function by direct cell
cell communication.
PMID- 9638331
TI - The apical lamina and its role in cell adhesion in sea urchin embryos.
AB - The hyaline layer (HL) is an extracellular matrix surrounding sea urchin embryos
which has been implicated in a cell adhesion and morphogenesis. The apical lamina
(AL) is a fibrous meshwork that remains after removal of hyalin from the HL and
the fibropellins (FP) are glycoproteins thought to be the principal components of
the AL. Using anti-FP antibodies (AL-1 and AL-2) we report immunoprecipitations
and affinity purifications yield a high molecular weight complex comprised of the
FP glycoproteins. The three components form a complex, stabilized by disulphide
cross-linking and have stochiometric ratios of 2 FPIa molecules to 1 each of FPIb
and FPIII. Pulse chase experiments indicate all 3 FP's are synthesized throughout
development with peaks in synthesis during cleavage and a sustained peak
beginning at hatching. Using immunogold and immunoperoxidase localization, the FP
localize to a fibrillar complex forming the innermost layer of the HL. In cell
adhesion experiments, cells adhere to affinity purified FP in a temperature, time
and concentration dependent manner. Cell adhesion to Fp is about 70% of that seen
when hyalin is used as a substrate. Pretreating with AL-1 and AL-2 reduces in
vitro cell adhesion by about 65%. We conclude FP's form a fibrillar complex,
which is synthesized throughout early development and functions, with other
components of the HL, as a substrate for cell adhesion.
PMID- 9638332
TI - Down-regulation of laminin-binding integrins by 1 alpha,25-dihydroxyvitamin D3 in
human melanoma cells in vitro.
AB - In the present investigation the effect of 1 alpha,25(OH)2D3 on the expression of
the integrin laminin receptor on the melanoma cell line SK-MEL-28 has been
examined. The SK-MEL-28 cells were shown to contain high-affinity receptors for 1
alpha,25(OH)2D3 and cell proliferation was found to be inhibited in a dose
dependent manner in response to the hormone. Using monoclonal antibodies against
the alpha 6-sub-unit of the integrin laminin receptor, immunocytochemistry
demonstrated that exposure of cells to 1 alpha,25(OH)2D3 for 5 days caused a
reduced staining intensity. This observation was further confirmed by dot blot
analysis, where a dose-dependent decline of alpha 6 expression was obtained after
treatment of the cells with 1 alpha,25(OH)2D3 for 6 days. FACS-analysis was
performed in order to quantify this decline, and it was found that the level of
alpha 6-subunits on the cell surface was reduced by more than 40%. Additional
investigations including Northern blot analyses of poly(A)+RNA extracts also
showed a dose-dependent reduction of alpha 6 mRNA. Interestingly, the decrease of
alpha 6 expression on the surface of SK-MEL-28 melanoma cells was accompanied by
a reduced ability of the cells to adhere to an artificial basement membrane. In
conclusion, the present investigation shows that besides having an
antiproliferative effect on the SK-MEL-28 melanoma cells, 1 alpha,25(OH)2D3 is
also able to inhibit the surface expression of the alpha 6-subunit of the
integrin laminin receptor. Moreover, the results strongly indicate that 1
alpha,25(OH)2D3 exerts its regulatory effect on the alpha 6-subunit at the
transcriptional level rather than at the protein level.
PMID- 9638333
TI - Maturation of cell-substratum focal adhesions induced by depolymerization of
microtubules is mediated by increased cortical tension.
AB - Dynamics of alterations of focal adhesions (FA) induced by a microtubule
depolymerizing drug, colcemid, was examined in several types of fibroblastic
cells. Evolution of individual FA in cultured cells was monitored by interference
reflection microscopy (IRM); at the end of the monitoring period (3 hours) the
cells were fixed and immunofluorescence microscopy of the same FA was performed
with an antibody against vinculin. Control and colcemid-treated cells remained
non-motile and did not show lamellipodial activity at the edges. During the
incubation, formation of new FA or disappearance of pre-existing FA did not occur
in either colcemid-treated or control cultures. However, FA in colcemid-treated
cells significantly increased in size in the course of a 3 hour incubation. The
growth of FA was centripetal and sometimes was accompanied by the fusion of
several adjacent FA. Immunofluorescence examination showed that colcemid-induced
growth of FA was accompanied by accumulation of several proteins specific for
these structures including vinculin, talin, paxillin and pp125FAK kinase.
Immunoblotting with anti-vinculin antibody showed that incubation with colcemid
considerably increased the amount of vinculin associated with the ventral
membranes due to its partial redistribution from a soluble pool into the growing
adhesions. A substantial increase in tyrosine phosphorylation of pp125FAK was
also observed in colcemid-treated cells. In cells plated on elastic silicone
rubber films, colcemid induced formation of wrinkles in the films and these
wrinkles relaxed after treatment with cytochalasin D. These results confirm that
microtubule depolymerization increases traction transmitted to the substratum by
the actin cortex and shows that an increase in cortical tension accompanies
maturation of FA. Taken together, these data show that short-term incubation with
colcemid does not affect the formation of initial FA. In contrast, microtubule
depolymerization considerably stimulates the maturation FA, manifested by their
centripetal growth. Maturation is proposed to be mediated by increased cortical
tension, which is caused by microtubule depolymerization.
PMID- 9638334
TI - Calcium-induced intercellular adhesion of keratinocytes does not involve
accumulation of beta 1 integrins at cell-cell contacts and does not involve
changes in the levels or phosphorylation of catenins.
AB - On initiation of terminal differentiation human epidermal keratinocytes detach
from the underlying basement membrane as a result of inactivation and subsequent
loss of integrins from the cell surface. Assembly of keratinocytes into
multilayered sheets requires functional E- and P-cadherin and when stratification
is inhibited in low calcium medium differentiating keratinocytes continue to
express functional integrins. Using immunofluorescence microscopy, we found that
on addition of calcium ions to keratinocyte monolayers there was colocalisation
of the beta 1 integrins and E-cadherin along the lateral membranes except for a
zone close to the substratum which exclusively contained integrins. Quantitative
immunoelectron microscopy showed that on induction of stable cell-cell contacts
the density of beta 1 integrins was the same on the apical and lateral membranes,
suggesting that the accumulation of integrins on the lateral membranes observed
by immunofluorescence microscopy is due to the increased area of contact between
adjacent cells and not to an increase in receptor density. There were no changes
in the levels of catenins and their degree of phosphorylation after induction of
cell-cell contacts. These observations provide new sights into the mechanism of
calcium-dependent intercellular adhesion of keratinocytes.
PMID- 9638335
TI - CD43 (sialophorin, leukosialin) shedding is an initial event during neutrophil
migration, which could be closely related to the spreading of adherent cells.
AB - Leukosialin is a negatively-charged mucin-like membrane protein of leukocytes.
This anti-adhesive molecule prevents uncontrolled cellular interactions and is
proteolytically cleaved during neutrophil activation. CD43 is shed in vivo during
neutrophil migration to the inflammatory site. We have analysed the decrease in
CD43 expression during in vitro adherence of TNF-alpha activated PMN. CD43 was
quantitated by flow cytometry on TNF-alpha-activated PMN either maintained in
suspension or allowed to adhere then detached with EDTA. Although TNF did not
induce significant modification of CD43 expression on suspended cells, we showed
that 40% of membrane CD43 is released during neutrophil TNF-induced adhesion to
serum-coated plates or endothelial cells, and that migration through the
endothelial monolayer did not result in further shedding. Adhesion-blocking anti
beta 2 integrin mAbs prevented CD43 shedding. beta 2 integrin "activation" by
anti-CD 18 mAbs or Mn ions did not decrease CD43 expression if adhesion was
prevented by stirring. Inhibitors of signal transduction or of cytoskeleton
association, which allowed cells to adhere but not to spread, inhibited the
shedding of CD43 during adhesion. We conclude that CD43 shedding is not promoted
by beta 2 integrins engagement or adhesion but is concomitant with spreading of
adherent cells.
PMID- 9638336
TI - Distinct location and prevalence of alpha-, beta-catenins and gamma
catenin/plakoglobin in developing and denervated skeletal muscle.
AB - We studied the distribution of alpha-catenin, beta-catenin and gamma
catenin/plakoglobin in developing, adult and denervated mouse skeletal muscle.
During primary myogenesis, all three catenins present a subsarcolemmal
distribution within primary myotubes. During secondary myogenesis they accumulate
at myotube-myotube contacts. In contrast to the other catenins, gamma-catenin is
strongly expressed in the sarcoplasm. In adult muscle, all three catenins are
localized on the presynaptic elements of the neuromuscular junction. In
denervated muscles, alpha- and beta-catenins are upregulated like N- and M
cadherin, while the levels of gamma-catenin/plakoglobin remain unchanged. The
developmental changes in localization and regulation of alpha- and beta-catenins
in muscle compared to gamma-catenin/plakoglobin are suggestive of a privileged
association of alpha- and beta-catenins with N- and M-cadherins, while gamma
catenin/plakoglobin appears to be expressed quite independently and must assume a
different role during myogenesis.
PMID- 9638337
TI - Desmosomes are regulated by protein kinase C in primary rat epithelial cells.
AB - In the present study, we addressed the possible relevance of protein kinase C
(PKC) in the regulation of intracytoplasmic desmosome assembly. Treatment of
cultured rat lingual and epidermal keratinocytes with a potent and highly
selective PKC inhibitor (GF109203X) induced an increase in granular labelling for
major desmosomal proteins, desmoplakins, desmoglein and plakoglobin, both
intracellularly and at the cell surface. This was associated with the formation
of ultrastructurally recognizable desmosomes deep in the cytoplasm and increase
in intercellular desmosome number. In contrast, PKC activation upon short
exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in altered cell
morphology, loss of intercellular contact and accumulation of desmosomal proteins
in the juxtanuclear zone. On the other hand, PKC depletion by long term TPA
treatment re-established cell-cell contact, where desmosomal markers were
exclusively redistributed. Taken together, these results suggest that inhibition
of PKC is required for intracytoplasmic as well as intercellular desmosome
assembly, whereas its activation may regulate disassembly process.
PMID- 9638338
TI - Cadherin mediated cell-cell adhesion is regulated by tyrosine phosphatases in
human keratinocytes.
AB - Normal Human Keratinocytes express on their cell surface E- and P-cadherins, two
Ca2+ dependent homophilic cell adhesion molecules that mediate keratinocyte
keratinocyte adherens junctions. In other cell types, adherens-type junctions are
reported to be major subcellular targets for tyrosine specific protein
phosphorylation (Volberg et al. (1991) Cell Regul., 2, 105-120) involving
tyrosine kinases and tyrosine phosphatases. We investigated the role of tyrosine
phosphatases in the regulation of cadherin mediated keratinocyte-keratinocyte
adhesion. We report the results of a wide tyrosine phosphatase inhibition using
pervanadate, a modified vanadate derivative known to inhibit most tyrosine
phosphatases. Keratinocytes treated with pervanadate, exhibit an important change
in cellular morphology and cadherins/catenins localization as shown by phase
contrast microscopy and immunocytochemistry. In this conditions, cadherins and
catenins no longer colocalize with the actin cytoskeleton of cells and the amount
of E-cadherin bound to the cytoskeleton decreases. A more intense phosphotyrosine
labelling is seen at the edges of the treated cells, suggesting that an increase
in the phosphorylation rate of some cadherin-catenin complex proteins induces a
diminished intercellular adhesion. Finally immunoprecipitation experiments of the
E-cadherin/catenin complex from pervanadate treated keratinocytes reveal an
increase in the tyrosine phosphorylation rate of E-cadherin, beta catenin and
probably gamma catenin. These data suggest an essential role for the protein
tyrosine phosphatases in keratinocyte intercellular junctions.
PMID- 9638339
TI - Dependence of neutrophil activation on cell density and adhesion.
AB - Upon an increasing cell density human neutrophils develop more cell-to-cell
contacts in conjunction with an increase in the pHi. These changes are
accompanied by decreased superoxide formation after adherence, and a decrease in
the total amount of 5-lipoxygenase products after various stimuli. Among the
various arachidonate metabolites, leukotriene formation remained almost constant
but the yield in 5-HETE decreased. This drop in could account for the decrease in
total 5-lipoxygenase products observed when the cell density increased. We
conclude that cellular signalling can be affected by an increase of cell-cell
interactions. Whether the increase in cellular pH is a cause or consequence of
such contact inhibition has yet be answered.
PMID- 9638340
TI - Early atherosclerotic plaques in the aorta following cytomegalovirus infection of
mice.
AB - We show here that BALB/c mice inoculated with murine cytomegalovirus (MCMV)
express viral antigens in the endothelial and smooth muscle cells of the aortic
wall, and that accumulation of inflammatory cells in the aortic lumen, similar to
that seen in early atherosclerotic lesions in humans, colocalizes with the site
of virus antigen expression. Immunosuppression of the mice at the time of virus
infection increased the expression of viral antigens and the size of early
atherosclerotic lesions in the intima. The percentage of the low-density
lipoprotein cholesterol (LDL-C), the major lipid contributor to atherosclerotic
plaques, was significantly increased in the serum of MCMV-infected mice, whether
or not the mice were fed a high cholesterol diet. Human cytomegalovirus (HCMV)
significantly increased the esterified cholesterol component of the total
cholesterol in a human arterial smooth muscle cell line infected in vitro with
HCMV. These results suggest that CMV infection is involved in two of the major
mechanisms that lead to development of atherosclerosis, i.e., immune injury and
high LDL-C.
PMID- 9638341
TI - Vinculin and cell-cell adhesion.
AB - Vinculin, a 117-kDa protein, is a constituent of adhesion plaques and adherence
junctions in non-muscle cells. We investigated the role of vinculin on the
physical strength of cell-cell adhesion by conducting disaggregation assays on
aggregates of parental wild-type F9 mouse embryonal carcinoma cells (clone BIM),
two vinculin-depleted F9 cell lines, gamma 227 and gamma 229, and a reconstituted
gamma 229 cell line (R3) that re-express vinculin. Immunoblotting demonstrated
that the four cell lines used in the study had similar expressions of the cell
cell adhesion molecule E-cadherin and associated membrane proteins alpha- and
beta-catenin. Double immunofluorescence analysis showed that, in contrast to the
vinculin-null cell lines. BIM and R3 cells expressed abundant vinculin at the
cell margins in adhesion plaques and in cell-cell margins that also contained
actin. Laminar flow assays showed that both the vinculin-positive and vinculin
negative cell aggregates that were formed in culture in the course of 24 to 48
hours largely remained intact despite the imposition of shear flow at high shear
rates. Since laminar flow imposed on cell aggregates act to separate cells from
each other, our data indicate that F9 cells that were adherent to a substrate
formed strong cell-cell adhesion bonds independent of vinculin expression. On the
other hand, aggregates of vinculin-depleted gamma 229 and gamma 227 cells that
were formed in suspension during a two-hour static incubation at 37 degrees C
were desegregated more easily with the imposition of shear flow than the BIM and
R3 cell aggregates formed under identical conditions. Loss of vinculin was
associated with a reduction in cell-cell adhesion strength only among those cells
lacking contact to a substrate. Overall, the results indicate that vinculin is
not needed for forming strong cell-cell adhesion bonds between neighboring
carcinoma cells which are adherent to the basal lamina.
PMID- 9638342
TI - A conserved role for L1 as a transmembrane link between neuronal adhesion and
membrane cytoskeleton assembly.
AB - The L1-family of cell adhesion molecules is involved in many important aspects of
nervous system development. Mutations in the human L1-CAM gene cause a
complicated array of neurological phenotypes; however, the molecular basis of
these effects cannot be explained by a simple loss of adhesive function. Human L1
CAM and its Drosophila homolog neuroglian are rather divergent in sequence, with
the highest degree of amino acid sequence conservation between segments of their
cytoplasmic domains. In an attempt to elucidate the fundamental functions shared
between these distantly related members of the L1-family, we demonstrate here
that the extracellular domains of mammalian L1-CAMs and Drosophila neuroglian are
both able to induce the aggregation of transfected Drosophila S2 cells in vitro.
To a limited degree they even interact with each other in cell adhesion and
neurite outgrowth assays. The cytoplasmic domains of human L1-CAM and neuroglian
are both able to interact with the Drosophila homolog of the cytoskeletal linker
protein ankyrin. Moreover the recruitment of ankyrin to cell-cell contacts is
completely dependent on L1-mediated cell adhesion. These findings support a model
of L1 function in which the phenotypes of human L1-CAM mutations results from a
disruption of the link between the extracellular environment and the neuronal
cytoskeleton.
PMID- 9638343
TI - Epitope mapping of a function-blocking beta 1 integrin antibody by phage display.
AB - Integrins are a major class of cell surface receptors involved in cell-cell and
cell-matrix adhesion and communication. Ha2/11 is a function-blocking anti-rat
beta 1 integrin hamster IgM that should be a useful reagent for understanding
beta 1 integrin function. We demonstrate that Ha2/11 cross reacts with human,
Xenopus, and Drosophila beta 1 integrins, and use phage display to map the
epitope for Ha2/11 to residues within the sequence LRSGEPQTF which lies 18 amino
acids proximal to the putative I domain in beta 1 integrins. Monoclonal antibody
mapping experiments, mutational analyses, and direct binding assays have
implicated integrin I domains in both cation and ligand binding. Our data
therefore suggest that Ha2/11 blocks beta 1 integrin function by interfering with
I domain-mediated ligand binding.
PMID- 9638344
TI - The biochemistry of gene therapy for AIDS.
AB - Gene therapy has enormous potential and could in the near future involve the
clinical biochemist in monitoring its efficacy. The involvement of clinical
biochemists in this field could be not only in evaluating the impact of a gene
based strategy on disease progression, but also in measuring the expression of
the products of therapeutic genes in treated individuals. Indeed, gene therapy
presents new possibilities for the treatment of many diseases and, in particular,
merits consideration in the treatment of a fatal disease like AIDS. The aim of
this paper is to review the biochemical basis and clinical relevance of the gene
therapy approaches directed towards the inhibition of human immunodeficiency
virus type-1. We discuss the goals which have been achieved, the problems which
have occurred and the efforts that are being made to solve them. In this regard,
particular attention is paid to new strategies targeting 'therapeutic' enzymes to
human immunodeficiency virus type-1 nucleic acids.
PMID- 9638345
TI - Reticulocytes and reticulated platelets: simultaneous measurement in whole blood
by flow cytometry.
AB - Reticulated platelets are a fraction of newly released circulating elements
characterized by a residual amount of RNA. It has been suggested that the
reticulated platelet count, providing an estimate of thrombopoiesis in the same
way as erythrocyte reticulocyte count is a measure of erythropoiesis, may be
useful in the study of thrombocytopenic disorders. Reticulated red cells and
platelets can be analyzed by flow cytometry using specific stains for nucleic
acids such as Thiazole Orange and Auramine-O. The aim of our work was to perform
the simultaneous evaluation of reticulated elements in whole blood using a
standard flow cytometer and to correlate the results obtained with a dedicated
cytometer. A group of 14 patients with abnormal absolute reticulocyte counts
(range 1.1-11%) and a group of 41 patients showing a platelet discrimination
error when analyzed with a dedicated flow cytometer (Sysmex R1000) were enrolled.
Linear amplification of both scatter and fluorescence was used to perform
reticulocyte count. A gate was set on platelet dimensions, and logarithmic
amplification of scatter and fluorescence was used to count reticulated
platelets. A good correlation was obtained both for results of reticulocyte count
(r2 = 0.9825) and for reticulated platelets (r2 = 0.8717) between our method and
those using dedicated instruments. These data show that reticulated platelet
count may be easily introduced in clinical laboratories that routinely perform
reticulocyte count by flow cytometry.
PMID- 9638346
TI - Salivary cortisol--an alternative to serum cortisol determinations in dynamic
function tests.
AB - Salivary cortisol was measured as an alternative to serum cortisol as a marker
for adrenocortical function following insulin tolerance test, corticotropin
releasing-hormone stimulation and adreno-corticotrophic hormone stimulation.
During insulin tolerance test and corticotropin-releasing-hormone stimulation
adreno-corticotrophic hormone was also measured. The tests were performed on
healthy control subjects as well as on patients under investigation for various
disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance
test: 3 controls on two occasions and 14 patients; corticotropin-releasing
hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone
stimulation: 6 controls and 10 patients). Five patients underwent both insulin
tolerance test and corticotropin-releasing-hormone stimulation. Using criteria
for adequate cortisol response in serum, the patients were classified as good or
poor responders. In 42 of the 45 tests performed the same conclusion as to
cortisol status was drawn when based on serum and salivary cortisol responses. In
healthy subjects and good responders the mean cortisol relative increase was
greater in saliva than in serum in all three tests (p < 0.05). Characteristic of
the results for the insulin tolerance test was a significant initial mean
decrease (p < 0.05), not found in serum, and the highest observed salivary
cortisol value was delayed for at least 30 minutes compared to that in serum.
Plasma adreno-corticotrophic hormone correlated significantly with the cortisol
concentrations determined 15 minutes later in serum (r = 0.54-0.64) and in saliva
(r = 0.76-0.85). The more pronounced cortisol response in saliva than in serum
and its closer correlation with adreno-corticotrophic hormone offer advantages
over serum cortisol, suggesting salivary cortisol measurement may be used as an
alternative parameter in dynamic endocrine test.
PMID- 9638347
TI - A time-resolved fluorescence immunoassay for the measurement of testosterone in
saliva: monitoring of testosterone replacement therapy with testosterone
buciclate.
AB - Monitoring of testosterone replacement therapy requires a reliable method for
testosterone measurement. Determination of salivary testosterone, which reflects
the hormone's biologically active plasma fraction, is a superior technique for
this purpose. The aim of the present study was to establish a new sensitive time
resolved fluorescence immunoassay for the accurate measurement of testosterone
levels in saliva and to validate it by monitoring testosterone replacement
therapy in eight hypogonadal men. A clinical phase I-study with the new ester
testosterone buciclate was performed to search for new testosterone preparations
to produce constant serum levels in the therapy of male hypogonadism. After two
control examinations eight male patients with primary hypogonadism were randomly
assigned to two treatment groups (n = 2 x 4) and given single doses of either 200
mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva
and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then
weekly for three months. The time-resolved fluorescence immunoassay for salivary
testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at
a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a
testosterone concentration of 305 pmol/l) and a good correlation with an
established radioimmunoassay of r = 0.89. The sample volume required by this
method is only 180 microliters for extraction and duplicate determination. The
assay procedure requires no more than three hours. In group I (200 mg)
testosterone did not increase to normal levels either in saliva or in serum.
However, in group II, androgen levels increased significantly and were maintained
in the normal range for up to 12 weeks with maximal salivary testosterone levels
of 303 +/- 18 pmol/l (mean +/- SE) and maximal testosterone levels of 13.1 +/-
0.9 nmol/l (mean +/- SE) in serum in study week 6 and 7. The time-resolved
fluorescence immunoassay for salivary testosterone provides a useful tool for
monitoring androgen status in men and women and is well suited for the follow-up
of testosterone replacement therapy on an outpatient basis. The long-acting ester
testosterone buciclate is a promising agent for substitution therapy of male
hypogonadism and in combination with testosterone monitoring in saliva offers an
interesting new perspective for male contraception.
PMID- 9638348
TI - External quality assessment of molecular biology-based methods used in
laboratories of clinical chemistry and human genetics.
AB - The Reference Institute of Bioanalysis of the German Society of Clinical
Chemistry has performed the first external assessment of molecular genetics
methods used in medical diagnosis. The following procedures were tested: (I) DNA
preparation from whole blood, (II) PCR amplification using "standard" primers,
and (III) submarine agarose gel electrophoresis. Out of 50 participants, 45
returned samples for evaluation.
PMID- 9638349
TI - Preoperative values of molecular coagulation markers identify patients at low
risk for intraoperative haemostatic disorders and excessive blood loss.
AB - Conventional laboratory investigations of haemostasis like prothrombin time and
activated partial thromboplastin time are not useful in predicting and managing
intra-operative bleeding complications. In order to establish a possible
"perioperative reference range" for thrombin generation prothrombin fragment F1+2
(F1+2) and fibrin degradation (D-dimer) markers, we measured F1+2 and D-dimer
concentrations before surgery (but after induction of anaesthesia), 30 minutes
into surgery, 10 minutes after the event expected to induce the maximal
activation of the haemostatic systems, 90 minutes after surgery and on
postoperative days 1 and 2 in 226 consecutive patients. Samples were collected
from arterial lines. Twenty patients developed a clinically defined,
intraoperative disorder of haemostasis, 206 did not. Patients with an
intraoperative disorder of haemostasis had significantly higher preoperative F1+2
and D-dimer concentrations. Preoperative values for F1+2 and D-dimer
concentrations above the 75th percentile of patients without an intraoperative
disorder of haemostasis indicated a 2.70 to 2.88 fold risk of developing an
intraoperative disorder of haemostasis (odds ratios were 3.04, 3.12 and 3.29 for
D-dimer, ELISA, F1+2, and D-dimer latex tests, respectively with 95% confidence
intervals from 1.20 to 8.46) with negative predictive values of 94%, but positive
predictive values of only 16% to 26%. These data suggest that preoperative
determination of molecular markers might be helpful in identifying a group of
patients at high risk for intraoperative disorder of haemostasis by exclusion of
low risk patients. Validation of such an approach requires a prospective trial.
PMID- 9638350
TI - Rifampicin causes false-positive immunoassay results for urine opiates.
AB - The treatment of tuberculosis usually includes the antibiotic rifampicin,
especially in patients with concomitant human immunodeficiency virus infection.
Some of these patients are in withdrawal therapy for drug abuse. When opiate
screening is carried out in patients receiving rifampicin, false positive results
are detected with the kinetic interaction of microparticles in solution method.
We evaluated this interference in a Cobas-Integra analyzer and found a 12% cross
reactivity of rifampicin for antibiotic concentrations ranging from 0.19 to 6.08
mumol/l (156 to 5000 micrograms/l). This effect is not explained by the colour of
the rifampicin solutions. Calculations assuming first order kinetics of
elimination show that more than 18 hours after a single oral dose of 600 mg of
rifampicin, a false positive result for opiates could be obtained. This indicates
that the risk of a false positive result must always be considered when urine
samples from these patients are analyzed.
PMID- 9638351
TI - Neuron-specific enolase: reference values in cord blood.
AB - With foetal sonography prenatal detection of tumours has become more frequent. To
evaluate and treat these infants it is necessary to identify the tumour
postnatally. Elevated neuron-specific enolase is a biochemical marker of
neuroblastoma. Since conditions during birth may influence neuron-specific
enolase concentration in foetal serum, specific reference values in cord blood
are required. Cord blood samples were taken from 192 healthy term newborns and
concentration of neuron-specific enolase was measured by enzyme immunoassay
(EIA). Median neuron-specific enolase concentration in the reference group was
8.0 micrograms/l and the 5th-95th percentiles were 4.8-19.4 micrograms/l. No
differences between male and female newborns were detected (p = 0.13).
Measurement of neuron-specific enolase in cord blood, in comparison with our
reference values, offers an early postnatal possibility of confirming the
diagnosis of neuroblastoma.
PMID- 9638352
TI - Additional Essential Criteria for Quality Systems of Medical Laboratories.
European Community Confederation of Clinical Chemistry (EC4) Working Group on
Harmonisation of Quality Systems and Accreditation.
AB - Essential Criteria for Quality Systems of Medical Laboratories have been
published recently by the European Community Confederation of Clinical Chemistry
(EC4) Working Group on Harmonisation of Quality Systems and Accreditation. The
Essential Criteria address the majority of critical aspects of quality management
in the medical laboratory. They have been accepted by the EC4 General Assembly
and are endorsed by the Forum of European Societies for Clinical Chemistry
(FESCC). However, a supplement to the Essential Criteria was necessary,
addressing two aspects, which are only partly covered by the Essential Criteria:
the management of resources and point of care testing. Thus, the EC4 Working
Group on Harmonisation of Quality Systems and Accreditation has decided to
formulate Additional Essential Criteria for Quality Systems of Medical
Laboratories, directed at the issues of management of resources and point of care
testing. Criteria on management of resources address financial aspects,
information logistics and acceptance by clients. Criteria on point of care
testing address responsibilities, education of non-laboratory staff and
operational aspects. The Additional Criteria are supplementary to the previously
published Essential Criteria and should be read as an integral part of these.
PMID- 9638353
TI - Low concentration monoclonal and oligoclonal bands in serum and urine using the
Sebia Hydragel Protein Electrophoresis System.
PMID- 9638354
TI - Neglected topics in eating disorders: guidelines for clinicians and researchers.
AB - Over the past few decades, there has been significant progress in research on
eating disorders that has informed the clinical management of these difficult,
and sometimes refractory, disorders. Indeed, sufficient progress has been made
such that practice guidelines have been offered to delineate standards of
clinical care and guidance to clinicians in the treatment of bulimia nervosa and
anorexia nervosa. Out of necessity, however, the practice guidelines are based on
a combination of research-based recommendations and clinical consensus because of
significant gaps in the extant research. Nonetheless, clinicians must confront
these clinical issues. The purpose of this special series is to address areas of
significant clinical importance that have a very modest research literature, and
to briefly summarize the existing research. The authors of the individual papers,
all noted experts in eating disorders treatment, then offer practical clinical
management recommendations drawing both on the modest available research and
their extensive clinical experience.
PMID- 9638355
TI - Enhancing motivation for change in treatment-resistant eating disorders.
AB - Denial and resistance to change are prominent features in most patients with
anorexia nervosa. The egosyntonic quality of symptoms can contribute to
inaccuracy in self-report, avoidance of treatment, difficulties in establishing a
therapeutic relationship, and high rates of attrition and relapse. Individuals
with bulimia nervosa are typically more motivated to recover, but often
ambivalent about forfeiting the ideal of slenderness and the protective functions
of binge-purge behavior. Few attempts have been made to assess denial and
resistance in the eating disorders, or to examine alternative strategies for
enhancing motivation to change. Review of the clinical literature indicates a
striking convergence of recommendations across conceptually distinct treatment
approaches. Clinicians are encouraged to acquire a frame of reference that can
help them understand the private experience of individuals with eating disorders,
empathize with their distress at the prospect of weight gain, and acknowledge the
difficulty of change. The Socratic method seems particularly well-suited to work
with this population because of its emphasis on collaboration, openness,
curiosity, patience, focused and systematic inquiry, and individual discovery.
Four themes are crucial in engaging reluctant eating-disordered clients in
therapy: the provision of psychoeducational material, an examination of the
advantages and disadvantages of symptoms, the explicit use of experimental
strategies, and an exploration of personal values.
PMID- 9638356
TI - Treatment of eating disorders in children and adolescents.
AB - Anorexia nervosa and bulimia nervosa are expressed differently in children and
adolescents than in adults. Consequently, diagnostic procedures and
multidisciplinary treatments need to be tailored to the unique developmental,
medical, nutritional, and psychological needs of children and adolescents with
eating disorders. This paper reviews current research outlining the differences
between child, adolescent, and adult eating disorders. Research is then reviewed
concerning the effectiveness of hospitalization, partial hospitalization,
individual dynamic therapy, cognitive-behavioral therapy, interpersonal therapy,
family therapy, and medication for treating anorexia nervosa, bulimia nervosa,
and related eating disorders in children and adolescents. Specific
recommendations are made for practitioners to tailor these treatments to their
eating-disordered child and adolescent patients, following a stepped-care,
decision-tree model of intervention that takes into account the effectiveness,
cost, and intrusiveness of the interventions.
PMID- 9638357
TI - Long-term course of anorexia nervosa: response, relapse, remission, and recovery.
AB - There is no predictable or normative long-term course associated with anorexia
nervosa. Some Individuals achieve complete recovery; others are ravaged by a
chronic disorder; and some die from it. Predicting course and outcome of anorexia
nervosa is complicated by the intrinsic complexity of the disorder; a lack of
shared terminology in studying the disorder; and a paucity of controlled clinical
treatment studies. This manuscript provides a review of the current state of
knowledge based on the long-term studies and discusses ways in which
methodological issues limit our ability to generalize more confidently regarding
the course and outcome of anorexia nervosa. In order to advance the field, we
need to bridge the gap between treatment outcome studies and naturalistic follow
up studies. Further we need to devine more carefully and consistently the
milestones of initial treatment response, relapse, remission, and recovery.
Building on previous works, criteria for each of these terms are proposed. Based
on existing studies, a discussion of treatment outcome and prognostic factors is
provided. Finally, clinical recommendations are provided for the clinician who is
responsible for the long-term care of an individual with anorexia nervosa.
PMID- 9638358
TI - Lymphocyte activation and effector functions. Web alert.
PMID- 9638359
TI - Germinal centers: form and function.
AB - Our understanding of the formation of germinal centers has advanced considerably
during the past year. Highlights include the elucidation of the role of cytokines
and chemokines in splenic organization and lymphocyte migration and their roles
in germinal center development. The functional consequences of recombination
activating gene re-expression in the germinal center have also been reported, as
have in vitro models of somatic mutation. Finally the resolution of the germinal
center reaction is being addressed by analysis of the individual cell types
produced.
PMID- 9638360
TI - Long-lived plasma cells: a mechanism for maintaining persistent antibody
production.
AB - Current models suggest that continuous antigenic stimulation of memory B cells is
required to maintain long-term antibody production. In view of recent
developments concerning plasma cell longevity, a new model is described that
incorporates the important role of long-lived plasma cells in sustaining
persistent antibody responses.
PMID- 9638361
TI - Regulation of interferon-gamma production by IL-12 and IL-18.
AB - IL-18 (interferon-inducing factor) and IL-12 exhibit a marked synergism in
interferon-gamma induction in T cells. Investigations into the mechanism of this
synergism have revealed that IL-12 upregulates expression of the IL-18 receptor
on cells producing interferon-gamma. Although IL-18 does not induce the
development of Th1 cells, it is essential for the effective induction and
activation of Th1 cells by IL-12. As for natural killer cells, IL-18 seems to
activate them independently of IL-12. Although IL-12 and IL-18 activate both
innate and acquired immunity, their excessive production by activated macrophages
may induce multiple organ disorders including disruption of the immune system.
PMID- 9638362
TI - Chemokines, lymphocytes and viruses: what goes around, comes around.
AB - Chemokines are believed to be the long-sought soluble mediators of selective
lymphocyte recruitment. As most selectin-integrin interactions are nonselective,
it is thought that the discrimination seen during lymphocyte infiltration into
tissues is brought about by the actions of distinct chemokines. Developments over
the past year have demonstrated the expanding roles of these factors in
lymphocyte chemoattraction, normal trafficking, and viral immunity.
PMID- 9638363
TI - JAK/STAT signaling by cytokine receptors.
AB - The JAK/STAT pathway is recognized as one of the major mechanisms by which
cytokine receptors transduce intracellular signals. This system is regulated at
multiple levels, including JAK activation, nuclear trafficking of STAT factors,
and negative feedback loops. Gene deletion studies have implicated selected STAT
factors as predominant mediators for a limited number of lymphokines. This
signaling pathway influences normal cell survival and growth mechanisms and may
contribute to oncogenic transformation.
PMID- 9638364
TI - Death-inducing functions of ligands of the tumor necrosis factor family: a
Sanhedrin verdict.
AB - Members of the tumor necrosis factor ligand family can kill cells in a rather
straightforward manner. They induce their receptors to recruit and activate
caspases, enzymes that are critically involved in the death process, and this
activation is further amplified by intracellular mitochondria-associated
mechanisms. The potentially hazardous expression of the ligands occurs widely in
the body; it is antigen-restricted only in the lymphocytes. Yet, in addition to
control modes affecting ligand expression, there are numerous inhibitory
mechanisms that act within target cells, to make doubly sure of avoiding an undue
'death verdict', while allowing the cells to exhibit other, noncytocidal effects
of the ligands.
PMID- 9638365
TI - Cytokine regulation of secondary lymphoid organ development.
AB - Lymphotoxin and tumor necrosis factor provide essential signals for the formation
of secondary lymphoid tissue structures. Lymphotoxin in its membrane form (LT
alpha 1 beta 2 heterotrimer) is required for the development of lymph nodes and
Peyer's patches and supports the development of normal spleen structure. In the
spleen, lymphotoxin acts during embryonic development to support the formation of
distinct B and T cell zones. Lymphotoxin also acts in a tonic fashion-supporting
the formation and maintenance of the follicular dendritic cell network and of
primary B cell follicle structure. The cells that deliver the tonic lymphotoxin
signal supporting follicular dendritic cell structure are B cells; thus, B cells
participate fundamentally in the development of the lymphoid tissue structure in
which they subsequently mature.
PMID- 9638366
TI - Natural killer cell receptors.
AB - In killing of cellular targets, natural killer cells employ receptors that
activate them and receptors specific for MHC class I that inhibit their
activation. Progress in understanding the inhibitory receptors has been rapid,
and indications are that they fall into two distinct structural types that appear
to utilize the same inhibitory signaling cascade; meanwhile, components of the
activation cascade are being elucidated, permitting us to integrate the pathways
involved.
PMID- 9638367
TI - Inhibitory signaling by B cell Fc gamma RIIb.
AB - The fact that B cells undergo feedback suppression, or negative signaling,
through the interaction of secreted antibody with specific antigen has been
extensively documented but the mechanisms involved in the process have been
elusive. Experiments over the past year using B cell deletion mutants and
dominant-negative enzymes have firmly established an important role for SH2
domain-containing inositol 5-phosphatase (SHIP) in negative signaling. Negative
signaling through SHIP appears to inhibit the Ras pathway through SH2 domain
competition with Grb2 and Shc and may involve consumption of intracellular lipid
mediators that act as allosteric enzyme activators or that promote entry of
extracellular Ca2+.
PMID- 9638368
TI - Negative regulation of T cell activation.
AB - T cell activation is negatively regulated by cytotoxic T lymphocyte antigen 4
(CTLA-4) and the killer cell inhibitory receptors. Endocytosis and signaling of
CTLA-4 are regulated by tyrosine phosphorylation. While T cell activation is
mediated by phosphorylation of immunoreceptor tyrosine-based activation motifs
and tyrosine kinases, inhibitory signals are delivered by tyrosine phosphatases.
Unresponsiveness is also induced by modulation of signaling components of the T
cell receptor complex.
PMID- 9638369
TI - GTPases in antigen receptor signalling.
AB - Immunological interest in small GTPases has focused for some years almost
exclusively on the role of Ras in promoting lymphocyte activation and
development. A new concept in this field is that GTPases are linked to multiple
biochemical effector signalling pathways and are consequently able to regulate
diverse cellular processes. It is also now recognised that GTPases other than Ras
regulate lymphocyte biology. Rap 1 has been suggested as a negative regulator of
lymphocyte responses and Rho GTPases are important components of signalling
pathways used by antigen receptors and by costimulatory, cytokine and chemokine
receptors to regulate the immune response.
PMID- 9638370
TI - Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of
cytokine receptor signaling.
AB - Recent findings have significantly advanced our understanding of the mechanism by
which the potent immunosuppressive drug rapamycin inhibits cytokine-dependent
lymphocyte proliferation. The protein targeted by the immunophilin-rapamycin
complex is a member of a newly defined family of phosphoinositide-3-kinase
related kinases. The rapamycin target protein functions as a protein kinase in a
signal transduction pathway that regulates the synthesis of proteins required for
cell-cycle progression in both lymphoid and nonlymphoid cells.
PMID- 9638371
TI - Adaptor proteins in lymphocyte antigen-receptor signaling.
AB - Adaptor molecules, proteins that possess no intrinsic enzymatic function, but
which mediate protein-protein interactions, have a critical role in integrating
signal transduction pathways following engagement of cell-surface receptors.
Several newly described adaptor molecules have been shown to serve important
functions in the regulation of signaling events initiated by lymphocyte antigen
receptors. Understanding how these adaptor proteins function to modulate
signaling cascades will provide important insights into the complex biology of
lymphocyte activation.
PMID- 9638372
TI - Long-range transcriptional regulation of cytokine gene expression.
AB - Most studies on the control of cytokine gene expression have involved the
functional analysis of proximal promoters. Recent work has identified distal
elements that mediate long-range cytokine gene regulation and has implicated
chromatin reorganization in regulation of cytokine gene loci. These studies have
begun to elucidate the basis for cell-specificity and high-level expression of
cytokine genes.
PMID- 9638373
TI - The regulation and roles of Rel/NF-kappa B transcription factors during
lymphocyte activation.
AB - The activation of B and T cells by a wide range of stimuli can rapidly induce
specific gene expression via a mechanism that promotes the nuclear translocation
of different Rel/nuclear factor-kappa B (NF-kappa B) transcription factors which
are normally resident in the cytoplasm. Recent findings highlight the crucial
roles of specific Rel/NF-kappa B family members in the processes of cell
division, apoptosis and differentiation that accompany lymphocyte activation.
PMID- 9638374
TI - Signaling checkpoints during the development of T lymphocytes.
AB - Two major lineage decisions face immature T cells as they develop in the thymus.
At an early stage in their development, they must first commit to either the
gamma delta or alpha beta lineages. If they opt for the alpha beta lineage, then
at a later stage they must also choose between a CD4+ or CD8+ fate before they
can pass through the thymic medulla and exit to the periphery. Thymocyte survival
at key developmental checkpoints is determined by signaling from cytokine
receptors and the T-cell receptor. Recent advances have been made in contemporary
understanding of the signals that regulate thymocyte survival, proliferation and
lineage decisions.
PMID- 9638375
TI - False-negative cervical smears: medico-legal fallacies and suggested remedies.
PMID- 9638376
TI - A case-control study of true-positive versus false-negative cervical smears in
women with cervical intraepithelial neoplasia (CIN) III.
AB - Cervical smears (n = 150) from five departments showing high-grade dyskaryosis
were examined by three cytologists. All the smears came from patients with biopsy
proven CIN III. One hundred had been correctly reported (true positives) but 50
had originally been reported as negative and had been found to be positive only
on review (false negatives). There were significant differences between the two
sets in the characteristics of the dyskaryotic cell population. The false
negative smears tended to have fewer than 200 dyskaryotic cells. The nuclei of
the dyskaryotic cells tended to have fine rather than coarse nuclear chromatin. A
smear with fewer than 50 dyskaryotic cells is 26 times more likely to be reported
as negative than one with more than 200 dyskaryotic cells. The results suggest
that there is a type of severely dyskaryotic smear that is inherently likely to
be missed on routine screening.
PMID- 9638377
TI - Personal performance profiles: a useful adjunct to quality assurance in cervical
cytology.
AB - In our laboratory, which processes approximately 40,000 smears annually, the
reporting patterns of each individual primary screener have been continuously
monitored over a 6-year period. The detection rates for minor abnormalities
(borderline/mild dyskaryosis) and major abnormalities (moderate dyskaryosis and
worse) are published quarterly in the laboratory. Individual continuous
monitoring rapidly identifies screeners with low detection rates. It is a useful
adjunct to existing methods of quality assurance; rescreening can be more
appropriately directed to smears reported by screeners with low detection rates.
It also identifies training needs and may be used to assess the value of update
courses for each screener. It is a faster method of identifying poor performance
than rapid review of all smears. The reporting rate of inadequate smears is also
calculated and published on a quarterly basis. This promotes a degree of
uniformity within the laboratory in the rate at which smears are reported as
inadequate, and also reduces the inadequate rate.
PMID- 9638378
TI - Achievable laboratory standards; a review of cytology of 99 women with cervical
cancer.
AB - The Working Party guidelines are a significant advance in the audit of the
National Health Service Cervical Screening Programme (NHSCSP), the priority of
which is to reduce mortality and morbidity from cervical cancer. This study was
undertaken to apply the guidance on review of screening history to a series of 99
women with invasive cervical cancer diagnosed in one centre during a 9 year
period. The majority (approx. 64%) of these women had not been screened within
the 5 years preceding diagnosis, 25% had negative, inadequate or abnormal smears
and 6% had previous treatment for cervical intraepithelial neoplasia (CIN). In
four patients diagnosis was delayed. No standards are yet available to test the
results of this series of women. Cervical cancer is relatively uncommon, and for
data to be aggregated and compared across the UK, it is important that strict
criteria are developed and applied to ensure that recruitment to the Working
Party categories is uniform and not open to local interpretation. Full review and
documentation of screening history should be mandatory for all women who develop
cervical cancer.
PMID- 9638379
TI - Evaluation of a statistically derived decision tree for the cytodiagnosis of fine
needle aspirates of the breast (FNAB).
AB - A decision tree for the diagnosis of FNAB was derived from defined human
observations using a rule induction method, C4.5 (a derivative of the ID3
algorithm). This algorithm is an implementation of the top-down induction method
where the tree is determined iteratively by adding those nodes and branches which
maximize the information gain at each step. The tree was derived from a training
set of 200 FNAB with known outcome using 10 defined features (from one observer)
and patient age. The tree contained a total of seven nodes (six observable
features and patient age) with eight endpoints (four benign, four malignant). The
tree was applied to a test set of 400 further FNAB with observations from the
training observer and produced a sensitivity of 95%, specificity of 93% and a
positive predictive value (PPV) of a malignant result of 89%. Four trainee
pathologists were given a training session on the observable features and then
used the tree to determine outcome in a further 50 FNAB. The observers were blind
to clinical details apart from age and the endpoints were coded with letters and
not labelled benign or malignant. The results from these observers produced
ranges of sensitivity 80-96%, specificity 64-92%, PPV 73-92% and kappa statistics
(with known outcome) 0.6-0.8. Reported difficulties in using the tree included
estimation of nuclear size. These results were worse than the performance of the
observers on a further 50 cases without using the decision tree (sensitivity 80
100%, specificity 72-100%, PPV 78-100%, kappa 0.72-0.92). The original 50 case
test set was rerandomized and the four trainee observers made all 10 defined
observations on each specimen without using the decision tree; these observations
were then used to derive decisions from the tree. The performance from this
method was similar to that using selected features from the tree, suggesting that
observation of all features together does not improve the reliability of each
specific observation. The poor performance of this tree suggests that this
methodology may be unsuitable for producing decision support aids for diagnostic
or training purposes in this domain.
PMID- 9638380
TI - A 3-year audit of thyroid fine needle aspirates.
AB - Fine needle aspiration (FNA) cytology is an important adjunct to the preoperative
management of thyroid swellings. It is a simple and highly cost effective
procedure with a higher sensitivity for the detection of malignancy than
ultrasound and radio-isotope scans. We audited a total of 208 aspirates performed
over a 3-year period. In our experience 61% of solitary thyroid swellings can be
diagnosed confidently on FNA cytology as either non-neoplastic (46%) or
neoplastic (15%). Based on these two groups the sensitivity is 91% and
specificity 94%. The specificity, however, decreases to 40% if the group reactive
vs neoplastic, which comprises 10-15% of cases and requires surgical
intervention, is included. The positive predictive value for malignant disease is
94% while the false-negative and -positive rates excluding the unsatisfactory and
reactive vs neoplastic groups are low at 2.7% and 5.4%, respectively (involving
non-neoplastic lesions and benign tumours only). There was no case of malignant
cytology with a benign biopsy follow up.
PMID- 9638381
TI - Pitfalls in the diagnosis of papillary carcinoma of the thyroid.
PMID- 9638382
TI - Fine needle aspiration (FNA) cytology in tuberculous lymphadenitis.
AB - Sixty-three lymph node aspirates were screened and 32 aspirates revealing
granulomatous lymphadenitis with or without caseation necrosis were re-evaluated.
The most characteristic morphological features among these cases were epithelioid
cell clusters with or without caseation necrosis. When clusters were thick,
careful observation of the periphery of the clusters helped to find epithelioid
cells. Caseation necrosis revealed a typical macroscopic and microscopic
appearance. Ziehl-Neelsen staining was negative in all smears and histological
sections. Polymerase chain reaction (PCR) amplification technique was applied to
23 of the cases in which the cytological diagnoses were consistent with
tuberculosis. Mycobacterium tuberculosis was demonstrated in 19 (82.60%) cases.
IN CONCLUSION: (i) it is necessary to perform several aspirations from different
sites of the enlarged lymph node; (ii) the diagnosis of 'granulomatous
lymphadenitis, consistent with tuberculosis' can be given, even though the acid
fast stains are negative; (iii) additional techniques such as PCR give supportive
information; (iv) an open biopsy is recommended if there is a discrepancy with
the clinical impression.
PMID- 9638383
TI - AFB staining in cytodiagnosis of tuberculosis without classical features: a
comparison of Ziehl-Neelsen and fluorescent methods.
AB - Fine needle aspirates (FNA) were obtained from lymph node and other sites in 250
suspected cases of tuberculosis. Twenty-four cases proved to be non-tubercular on
FNA smears and served as negative controls. Of the smears obtained from the
remaining 226 cases, 233 were classified into five groups based on
cytomorphological features, i.e. presence of necrosis and granulomas, necrosis
alone or acute inflammatory exudate (AIE) with or without granuloma. Cases with
AIE alone formed the largest group (n = 123). Staining for AFB was done by Ziehl
Neelsen (ZN) and fluorescent methods in all 250 cases. A correlation of AFB
positivity and its semiquantitative scoring (1+ to 3+) with the cytomorphological
spectrum was done. Overall AFB positivity by ZN staining was 33.5% and by
fluorescent staining 45.4%. When the two methods were combined, AFB positivity
was 58.7%. Fluorescent staining was superior to the ZN stain in the presence of a
low bacterial load as seen in smears with diagnostic cytomorphological features
of tuberculosis. In problem areas like AIE alone or with occasional granulomas,
AFB positivity by ZN staining is nearly as good as the fluorescent method,
because the bacterial load is high.
PMID- 9638384
TI - Fine needle aspiration diagnosis of subcutaneous and osteolytic rhinosporidiosis.
PMID- 9638385
TI - Drug-food interactions in hospitalised patients. Methods of prevention.
AB - Drug-food interactions in hospitalised patients may result in decreased drug
efficacy or increased drug toxicity. The increasing complexity of drug therapy
regimens has increased the potential for drug-food interactions to occur,
reinforcing the need to develop methods to prevent clinically significant drug
food interactions. Before selecting the optimal method, in terms of feasibility
of implementation and successful outcome, drugs with the potential for clinically
significant interactions with food must be identified. From an analysis of the
literature, 6 methods to prevent drug-food interactions have been suggested as
useful tools. Each method has its own advantages and disadvantages. Most have
been developed in response to guidelines from the most well recognised agency for
quality review in the US, the Joint Commission on Accreditation of Healthcare
Organisations (JCAHO). Based on those recommendations, an ideal programme to
prevent drug-food interactions would be a combined patient counselling and label
system to select the most appropriate drug administration times and increase
nurse and patient awareness of the potential for drug-food interactions. However,
because of time constraints and limited resources, a label system or the
provision of a drug-food interaction pamphlet to the patient before discharge
would be a more practical method. Newsletters and educational in-services
combined with patient counselling or a label system would be a valuable method to
prevent drug-food interactions in hospitalised patients.
PMID- 9638386
TI - A risk-benefit assessment of irinotecan in solid tumours.
AB - Irinotecan is a water-soluble camptothecin analogue. Its cytotoxicity effects are
exerted through interaction with the topoisomerase I-DNA complex, eventually
leading to cell death. In preclinical studies, irinotecan has demonstrated a
broad spectrum of activity in vitro and in vivo, and synergistic effects have
been observed when it is administered in combination with other antineoplastic
agents. Phase I studies of irinotecan conducted in Europe, Japan and the US have
provided useful information on optimal dosage and scheduling, as well as thorough
evaluation of the toxicity profile of the drug. Phase II and III trials utilising
either irinotecan alone or in innovative combinations with other drugs are
currently in progress. Available data indicate that irinotecan alone or in
combination with other cytotoxic agents has therapeutic potential in several
types of malignancy, including colorectal, lung, ovarian, cervical and gastric
cancers and non-Hodgkin's lymphoma. It is the first drug since fluorouracil to
possess consistent antitumour activity against metastatic colorectal cancer. The
principal toxicities associated with irinotecan are diarrhoea and leucopenia.
Effective strategies have been developed to circumvent both the early- and
delayed-onset diarrhoea induced by irinotecan, thus allowing safer delivery of
this promising agent in the clinical setting.
PMID- 9638387
TI - A risk-benefit assessment of pharmacological treatments for panic disorder.
AB - Panic disorder, a psychiatric disorder characterised by frequent panic attacks,
is the most common anxiety disorder, affecting 2 to 6% of the general population.
No one line of treatment has been found to be superior, making a risk-benefit
assessment of the treatments available useful for treating patients. Choice of
treatment depends on a number of issues, including the adverse effect profile,
efficacy and the presence of concomitant syndromes. Tricyclic antidepressants
(TCAs) are beneficial in the treatment of panic disorder. They have a proven
efficacy, are affordable and are conveniently administered. Adverse effects,
including jitteriness syndrome, bodyweight gain, anticholinergic effects and
orthostatic hypotension are commonly associated with TCAs, but can be managed
successfully. Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors
are also potential first line agents and are well tolerated and effective, with a
favourable adverse effects profile. There is little risk in overdose or of
anticholinergic effects. Adverse effects include sedation, dyspepsia and headache
early in treatment, and sexual dysfunction and increased anxiety, but these can
be effectively managed with proper dosage escalation and management.
Benzodiazepines are an effective treatment, providing short-term relief of panic
related symptoms. Patients respond to treatment quickly, providing rapid relief
of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and
psycho-motor impairment. There are reservations over their first-line use because
of concerns regarding abuse and dependence. Monoamine oxidase inhibitors, because
of their adverse effects profile, potential drug interactions, dietary
restrictions, gradual onset of effect and overdose risk, are not considered to be
first-line agents. They are effective however, and should be considered for
patients with refractory disease. Valproic acid (valproate sodium), while not
intensively studied, shows potential for use in panic disorder. More studies are
needed in this area before the available data can be confirmed. As a supplement
to drug therapy, cognitive behavioural therapy is effective. It is well
tolerated, and may be beneficial in certain clinical situations. Its main
drawback is the time commitment and effort needed to be made by the patient.
PMID- 9638388
TI - Minocycline-induced pigmentation. Incidence, prevention and management.
AB - Pigmentation is a well recognised adverse effect of minocycline therapy. Various
body sites, most notably the skin, nails, bones, thyroid, mouth and eyes are
affected and the pigmentation may appear at multiple sites. In general,
pigmentation results from long term administration of minocycline at cumulative
doses greater than 100 g, although cutaneous or oral mucosal pigmentation may
appear, regardless of dose or duration of therapy. When the skin is involved, the
blue-black pigmentation develops most frequently on the shins, ankles and arms.
Other patterns of skin involvement include pigmentation that is either
generalised and symmetrical, or that develops at sites of inflammation. The bones
of the oral cavity are probably the most frequently affected sites of
pigmentation affecting greater than 20% of patients taking minocycline for more
than 4 years. In contrast, the oral mucous membranes and teeth are infrequently
pigmented from minocycline. Ocular, thyroid and visceral pigmentation is also
relatively uncommon and usually develops only with high doses and long term
minocycline use. Whereas pigmentation of the skin and oral mucosa is generally
reversible when the drug is discontinued, the pigmentation is often permanent
when other sites are involved. Although minocycline-induced pigmentation is not
harmful, the drug should be discontinued when the adverse effect is recognised.
All patients receiving minocycline, especially those treated for longer than 1
year, require screening for the development of pigmentation.
PMID- 9638389
TI - Drug administration in patients with diabetes mellitus. Safety considerations.
AB - Diabetes mellitus is associated with alterations in a number of key metabolic
pathways. Despite theoretical concerns, clinically significant alterations in the
pharmacokinetic properties of commonly prescribed drugs are relatively uncommon.
Indeed, dose adjustment is rarely required in the setting of well controlled
diabetes mellitus. However, significant alterations in drug handling may occur in
the context of poor metabolic control or in the presence of complications such as
nephropathy. Metformin use may be complicated by lactic acidosis. Fortunately,
this is a rare occurrence providing that the agent is not used in circumstances
in which it is contraindicated. Indeed, the risk of death from metformin-related
lactic acidosis is similar in magnitude to the risk of death related to
hypoglycaemia in sulphonylurea-treated patients. The novel hypoglycaemic agent
troglitazone may be associated with abnormalities in liver function in
approximately 2% of patients. Discontinuation of treatment is followed by
normalisation of liver enzyme levels. Current prescribing information recommends
frequent monitoring of liver function tests and immediate cessation of therapy if
abnormalities develop. In addition to disturbances in intermediary metabolism,
diabetes mellitus may also lead to chronic microvascular and marcovascular
complications. Thus, in addition to the use of drugs for the control of blood
glucose, patients with diabetes mellitus are likely to be prescribed medication
for associated conditions such as cardiovascular disease. Such medication
includes the ACE inhibitors which are contraindicated in patients with bilateral
renal artery stenosis. This complication may be theoretically more common in
patients with diabetes mellitus because of accelerated atherosclerosis. However,
in clinical practice this is an uncommon occurrence in the absence of clinical
features that should alert the treating clinician that an individual patient
might be at high risk. Although caution should also be used with beta-blocker
therapy in patients with diabetes mellitus, current evidence suggests that, like
ACE inhibitors, these drugs may be particularly useful in this patient group.
PMID- 9638391
TI - The ELITE Study. What are its implications for the drug treatment of heart
failure? Evaluation of Losartan in the Elderly Study.
AB - Angiotensin II type 1 (AT1) receptor antagonists inhibit the renin-angiotensin
system more completely than ACE inhibitors, and do not increase bradykinin levels
as ACE inhibitors do. ACE inhibitors have been proven to increase survival and
improve quality of life in patients with congestive heart failure (CHF). At the
48-week follow-up of the Evaluation of Losartan in the Elderly (ELITE) Study, the
AT1 receptor antagonist losartan (at a dosage of 50 mg/day) was found to be
superior to captopril 50 mg 3 times daily in terms of its effects on total
mortality, total mortality and/or hospitalisation for CHF, and hospitalisation
for any reason. Hospitalisation for CHF was the same for both drugs. Adverse
effects occurred in 12 and 21% of those receiving losartan and captopril,
respectively. Cough, rash, angioedema or taste disturbances/reduced appetite
prompted the cessation of drug treatment in 0 and 7% of those receiving losartan
and captopril, respectively. Until additional data are available, this author
recommends that elderly patients with CHF and an abnormal or normal left
ventricular ejection fraction, and who are unable to tolerate ACE inhibitors,
should receive losartan 50 mg/day.
PMID- 9638390
TI - Pain treatment in multimorbid patients, the older population and other high-risk
groups. The clinical challenge of reducing toxicity.
AB - The prevalence of pain is high in multimorbid patients and they can experience a
multitude of painful conditions. The changes in physiology and homeostasis
associated with multimorbidity and increasing age and the immature metabolism of
neonates all increase the risk of toxicity from analgesics. Altered
pharmacokinetics and metabolism influence drug pharmacodynamics and therapeutic
windows. Imbalances in local homeostatic mechanisms increase local toxicity. The
gastrointestinal organs and the kidney have a major role in the absorption,
metabolism and excretion of analgesics and changes in their function predispose
individuals to adverse effects. Knowledge of such compromise should influence the
choice of analgesic, the administration regimen and the mode of application. The
mainstay of chronic pain treatment are 3 classes of drugs: nonsteroidal anti
inflammatory drugs (NSAIDs), opioids and a host of so-called adjuvant drugs,
which are used to enhance the analgesic action of the classic analgesics. In each
class a wide range of drugs are available, that differ in pharmacokinetic and
pharmacodynamic characteristics. These differences can be exploited to either
increase analgesic efficacy and reduce toxicity, or to minimise the interference
of pain therapy with daily life. Clinically important differences in analgesic
and toxic effects between drugs in each analgesic class will be discussed in this
article from the perspective of reducing adverse effects. New knowledge
concerning the mechanism of action of analgesics and their metabolites is making
the specific selection of NSAIDs and opioids to reduce adverse effects in
multimorbid, chronic pain patients possible.
PMID- 9638392
TI - Alpha 1-antitrypsin. Hope on the horizon for emphysema sufferers?
AB - Alpha 1-Antitrypsin (alpha 1AT) deficiency is the most common genetic cause of
liver disease in children and emphysema in adults. Therapy for pulmonary disease
attributable to alpha 1AT deficiency includes alpha 1AT augmentation therapy
along with supportive measures. The alpha 1AT preparation that is currently used
for therapy is derived from fractionated plasma. The results of clinical trials
suggest that augmentation therapy with alpha 1AT slows the progression of
emphysema and causes few adverse events. Patients with plasma levels of alpha 1AT
that are < 11 mumol/L and who have airway obstruction should be considered for
augmentation therapy. Novel approaches include the administration of aerosolised
alpha 1AT, recombinant alpha 1AT, gene therapy and synthetic elastase inhibitors.
PMID- 9638393
TI - Drug therapy in haemodialysis patients. Special considerations in the elderly.
AB - End-stage renal disease (ESRD) is the stage of renal failure at which an
individual requires dialysis therapy or a renal transplant to survive. The
prevalence of ESRD is disproportionately higher among patients aged > 65 years,
and the average age of new ESRD patients is continually rising in the US Medicare
population. Medication management in this population is challenging because of
the combination of multiple comorbid disease states, a plethora of medications
and the added dimension of dialysis therapy, as well as pharmacokinetic and
pharmacodynamic changes attributable to the aging process. Cardiovascular
disorders such as hypertension, coronary artery disease, congestive heart failure
and arrhythmias are common in elderly patients with ESRD, and account for most of
the deaths in this population. Constipation is common in patients aged > 65
years, and its incidence is even higher among those receiving dialysis. Pain
management is of particular concern because elderly dialysis patients are
frequently prescribed inappropriate pain relief regimens. Many healthcare
practitioners do not realise that patients with uraemia are at a higher risk of
bleeding caused by nonsteroidal anti-inflammatory drugs than are patients with
normal renal function. In addition, most practitioners do not appreciate that
virtually all opioids (narcotics) and their active metabolites accumulate in
patients with renal failure, leading to an increased risk of narcosis. Infectious
complications are frequent in the ESRD population, with dialysis access
infections and pneumonia being the 2 most common infections seen in hospitalized
patients receiving dialysis treatment. The establishment of vaccination
programmes for the prevention of hepatitis B, influenza and pneumococcal
infections is important because of the increased risk of these disease in this
population. Unfortunately, these high-risk patients display, in general, a
decreased immunogenic response to vaccinations. This article addresses some of
the practical issues that surround the medication management or prevention of
these particular diseases in elderly patients undergoing haemodialysis.
Specifically, we discuss the pharmacokinetic and pharmacodynamic changes that
occur with specific medications in such patients. Drug dialysability is also
discussed.
PMID- 9638394
TI - The use of drugs for cardioversion of recent onset atrial fibrillation and
flutter. Focus on ibutilide.
AB - Atrial fibrillation (AF) is the most common sustained arrhythmia, particularly in
the elderly population. It is well recognised that AF is a major cause of stroke,
even in the absence of underlying heart disease. Although AF and atrial flutter
share many causes and may be seen in the same patient, there are differences
between these arrhythmias: atrial flutter is less common, and the risk of stroke
associated with it is less than that with AF. In addition to stroke, both AF and
atrial flutter may cause cardiomyopathy, which may be fully reversible with
effective treatment of the arrhythmia. Both AF and atrial flutter can result in
severe symptoms and may precipitate heart failure, ischaemia and syncope. Recent
research indicates that AF is a self-perpetuating arrhythmia, and that the longer
it is left untreated the less likely it is that effective cardioversion will be
possible. Drugs are an attractive option for the cardioversion of AF and atrial
flutter because their use does not require anaesthesia. Antiarrhythmic drugs in
class III of the Vaughan-Williams classification are effective in the treatment
of AF, but they have adverse effects; several new 'pure' class III agents are
under development. The first of these to be made available is ibutilide, a
methanesulphonamide derivative. Initial results are encouraging, particularly for
atrial flutter. However, the drug has the potential for proarrhythmic effects and
physicians who use it will need to be aware of these.
PMID- 9638395
TI - Pathogenesis and treatment of glucocorticoid-induced osteoporosis.
AB - Aging is associated with a marked decline in bone mineral density (BMD), an
increased likelihood of falling and a much greater propensity for fracture.
Several factors contribute to aging-related bone loss, including reduced bone
formation, increased bone resorption, recent bodyweight loss, poor nutritional
status and the coexistence of other, often rheumatological, conditions. Any of
these factors can lead to an uncoupling of the bone remodelling unit. In
addition, the frequent use of glucocorticoids to treat a vast array of conditions
has contributed to an ever-expanding group of elderly individuals who are at
extremely high risk for spine and hip fractures. Owing to the surprisingly high
morbidity and mortality associated with these fractures in the elderly, an
understanding of the pathogenesis and epidemiology of glucocorticoid-induced
osteoporosis is paramount. The factors that contribute to bone loss in older
individuals treated with glucocorticoids include reduced muscle mass, poor
nutrition, hypogonadism, vitamin D deficiency and secondary hyperparathyroidism.
Recent studies suggest that a prophylactic approach to this problem could have a
huge impact on the medical, social and economic costs of osteoporosis.
PMID- 9638396
TI - Important drug-drug interactions in the elderly.
AB - Although drug-drug interactions constitute only a small proportion of adverse
drug reactions, they are important because they are often predictable and
therefore avoidable or manageable. Their frequency is related to the age of the
patient, the number of drugs prescribed, the number of physicians involved in the
patient's care and the presence of increasing frailty. The most important
mechanisms for drug-drug interactions are the inhibition or induction of drug
metabolism, and pharmacodynamic potentiation or antagonism. Interactions
involving a loss of action of one of the drugs are at least as frequent as those
involving an increased effect. It is likely that only about 10% of potential
interactions result in clinically significant events and, while death or serious
clinical consequences are rare, low-grade, clinically unspectacular morbidity in
the elderly may be much more common. Nonspecific complaints (e.g. confusion,
lethargy, weakness, dizziness, incontinence, depression, falling) should all
prompt a closer look at the patient's drug list. There are a number of strategies
that can be adopted to decrease the risk of potential clinical problems. The
number of drugs prescribed for each individual should be limited to as few as is
necessary. The use of drugs should be reviewed regularly and unnecessary agents
withdrawn if possible, with subsequent monitoring. Patients should be encouraged
to engage in a 'prescribing partnership' by alerting physicians, pharmacists and
other healthcare professionals to symptoms that occur when new drugs are
introduced. Physicians with a responsibility for elderly people in an
institutional setting should develop a strategy for monitoring their drug
treatment. For those interactions that have come to clinical attention, it is
important to review why they happened and to plan for future prevention.
Clinicians should also report, via the appropriate postmarketing surveillance
scheme, any drug-drug interactions they have encountered. Finally,
multidisciplinary education about the nature of physiological aging and its
effect on drug handling, and the possible presentations of drug-related disease
in older patients, is an important element in reducing interactions in the
elderly.
PMID- 9638398
TI - Current and future therapies for HCV infection: what should the end point for
treatment be?
AB - Based upon all of the available data relating to the natural history, chemical
course, and response to therapy of HCV, the following recommendations are made:
1) The primary end point for HCV therapy should be HCV clearance from all tissue
sites, eg plasma, liver and others 2) Therapy should be provided for patients
with early infections as they have the best chance of achieving a virologic
response 3) Therapy should be offered to patients with cirrhotic disease, as
prevention of hepatic decompensation and degeneration to hepatic cancer is
possible 4) End stage decompensated disease should be treated, particularly if
liver transplantation is being considered, in an effort to either eliminate or
ameliorate disease recurrence 5) Combination therapies are preferable to
monotherapy as they enhance the likelihood of a therapeutic response. Some of
these include agents that reduce the frequency of IFN-induced untoward events
(NSAIDs) 6) The approach to HCV infection should be to view it as an infectious
disease. In this way, multi-agent therapy could be used to prevent the emergence
of drug resistant mutants as well as to obtain earlier clearance of the infection
than is possible with monotherapy.
PMID- 9638397
TI - Pramipexole. A review of its use in the management of early and advanced
Parkinson's disease.
AB - Pramipexole is an orally active non-ergoline dopamine agonist with selective
activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4
receptor subtypes) and with preferential affinity for the D3 receptor subtype. It
is approved as monotherapy in early Parkinson's disease and as adjunctive therapy
to levodopa in patients with advanced disease experiencing motor effects because
of diminished response to levodopa. The potential neuroprotective effects of
pramipexole have been shown in animal and in vitro studies. Data from relatively
long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to
6.0 mg/day) can improve activities of daily living and motor symptoms in patients
with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36
weeks), as an adjunct to levodopa in advanced disease, improved activities of
daily living and motor symptoms, reduced the duration and severity of 'off'
periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood
[Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test
were not significantly improved. The extent of disability improved according to
the UPDRS parts II and III but, when assessed by secondary efficacy parameters,
it is unclear whether disability or the severity of disease improved. No
significant differences were observed in patients randomised to pramipexole or
bromocriptine according to a secondary hypothesis in a prospective study in which
both drugs were better than placebo. Some quality-of-life measures improved with
active treatment relative to placebo. Further studies comparing pramipexole with
other dopamine agonists and levodopa in patients with early and advanced
Parkinson's disease would be useful. In pramipexole recipients with early
disease, the most commonly experienced adverse events were nausea, dizziness,
somnolence, insomnia, constipation, asthenia and hallucinations. The most
commonly reported adverse events in pramipexole recipients with advanced disease
were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a
worsening of the Parkinson's disease), dizziness, hallucinations, accidental
injury, dream abnormalities, confusion, constipation, asthenia, somnolence,
dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency.
The incidence of some adverse events did not greatly differ between pramipexole
and placebo recipients. CONCLUSIONS: Pramipexole is effective as adjunctive
therapy to levodopa in patients with advanced Parkinson's disease. However, the
potential beneficial effects of pramipexole on disease progression need to be
confirmed in clinical studies. The efficacy of pramipexole monotherapy in
patients with early disease has also been demonstrated, although the use of
dopamine agonists in early Parkinson's disease remains controversial.
PMID- 9638399
TI - Treatment of HCV positive individuals with normal serum ALT levels.
AB - A substantial number of cases of chronic hepatitis C infection can be shown to
have normal or near normal serum ALT levels. Major questions that arise when such
cases are seen are: should such patients be treated; if so for how long; and what
is the end point of therapy. The reported experience of such patients treated by
IFN is reviewed.
PMID- 9638400
TI - Use of interferon for the treatment of chronic hepatitis C in the elderly.
AB - Hepatitis C virus is a worldwide health care problem. It affects all age groups.
Many patients have had the infection for 20-30 years before they present for
therapy. With a peak incidence of disease in the 30-40 year age group, it is
obvious that a large number of cases must occur in the elderly (age > 65 years).
Of these, a fraction progress to cirrhosis and hepatocellular carcinoma.
Interferon is the only agent approved for use in patients with chronic hepatitis
C. The efficacy of interferon in younger patients is reported to be 50%. Half of
these will experience a relapse within 1 year. There are few studies assessing
the role of interferon used for elderly patients with chronic hepatitis C. The
reported response rate to interferon in elderly patients was 60%, with 30% having
a virologic/complete response. These studies demonstrate that the elderly
tolerate interferon reasonably well. No significant differences have been
reported between elderly and young treatment groups.
PMID- 9638401
TI - Treatment of chronic hepatitis C in individuals with pre-existing or confounding
neuropsychiatric disease.
AB - The problems associated with the recognition and management of chronic hepatitis
C in a population of individuals with confounding psychiatric disease are
identified. The experience of treating such patients and the psychotropic
medication required during treatment are reviewed.
PMID- 9638402
TI - The interaction of alcoholic liver disease and hepatitis C.
AB - The following article reviews available data of the interaction of alcohol
related liver disease and hepatitis C viral infection as well as special
considerations for the treatment of these patients. Alcohol worsens the degree
and accelerates the progression of hepatic injury, enhances the risk of
developing hepatocellular carcinoma and decreases response to interferon therapy.
Patients with hepatitis C should avoid alcohol ingestion.
PMID- 9638403
TI - Interferon treatment of HCV positive cirrhotic patients.
AB - An estimated 3.5 million people in the United States have chronic hepatitis C.
Each year, 8,000 to 10,000 of these chronically infected patients die of a liver
related complication of their infection. The introduction of effective blood
screening assays has resulted in a remarkable decrease in the incidence of post
transfusion HCV infection. Nonetheless, hepatitis C remains an important clinical
problem. Some important new treatment programs can help prevent the development
and progression of compensated cirrhosis to either decompensated cirrhosis or
HCC. Patients who present to the health care system with advanced chronic active
hepatitis or cirrhosis have been treated with interferon. Of those studied, only
IFN therapy has been shown to induce remissions of the hepatic inflammatory
process and to eliminate viral infection in most treated cases. However, it is
widely held assumption that cirrhotic individuals do not respond to IFN therapy
and that the treatment of decompensated cirrhotic individuals with HCV infection
is dangerous. We believe that this assumption is false. In many studies,
cirrhotic patients with chronic hepatitis C have been shown to respond to IFN
therapy. However, they do so at a rate of half that reported for individuals with
non-cirrhotic chronic active hepatitis. There have been no reports of hepatic
decompensation as a consequence of IFN treatment of cirrhotic individuals with
chronic hepatitis C. The use of IFN for cirrhotic patients is reviewed.
PMID- 9638404
TI - Interferon treatment of children with chronic hepatitis C.
AB - Hepatitis C virus (HCV) is the major cause of acquired non-A, non-B hepatitis.
Interferon is becoming the standard treatment in adults for chronic hepatitis C,
however, the experience with interferon treatment in children is very limited.
The review article describes the current approach in the management of children
with chronic hepatitis C infection and the review of the literatures.
PMID- 9638405
TI - Role of iron in the natural history and clinical course of hepatitis C disease.
AB - The following review evaluates the current data implicating a role for hepatic
iron in enhancing the liver injury in patients with chronic hepatitis C
infection. Iron removal lowers transaminases, but doesn't appear to improve
responsiveness to interferon-alpha therapy. An important effect of iron removal
might be to delay progression of liver injury to fibrosis and cirrhosis. Until
such a hypothesis is disproven, phlebotomy therapy for even mildly iron-loaded
HCV patients is recommended.
PMID- 9638406
TI - Biology, physiology and physiopathology of clamping during liver surgery.
AB - Liver surgery is currently performed with minimal morbidity and mortality, mostly
thanks to reduced intraoperative blood loss, achievable by various types of liver
clamping. A better knowledge of the physiological and physiopathological changes
caused by liver clamping is however still necessary. The "natural" evolution of
biochemical and liver function tests after liver surgery have been described.
This paper describes the hemodynamic changes observed with different types of
clamping and discusses several ways in which liver clamping techniques might be
improved.
PMID- 9638407
TI - Major liver resections without vascular clamping: retrospective study of 84
cases.
AB - BACKGROUND/AIMS: The question as to whether vascular clamping aggravates
mortality and morbidity of major liver resection was investigated in this study.
Major liver resection with vascular clamping for parenchyma transection has
mortality between 0 and 5%, and higher morbidity reaching 47% with healthy liver
in recent report. METHODOLOGY: Eighty-four major liver resection without vascular
clamping were carried out between January 1986 to December 1996 were reviewed.
There were 57 men and 27 women with average age of 58.2 (12.2) years old.
Indications of resection were adenoma (4.8%) angioma (11.9%) focal nodular
hyperplasia (1.2%) hematoma (1.2%) metastases (60.7%) hepatocellular carcinoma
(14.3%) and cholangiocarcinoma (5.9%). Resections used ultrasonic dissector
(Sonoca) with intraoperative ultrasonography were right hepatectomy in 56 cases
extended right hepatectomy in 10 cases left hepatectomy in 17 cases and middle
hepatectomy in 1 case. Remnant liver was cirrhotic in 3 cases. RESULTS: Three
patients died (3.5%) and the rate of major complications were 11.2%. 46 patients
(54.8%) had no blood transfusion. The mean of blood transfusion was 1.5 (2.7)
units. The mean of operative length was 286.23 (63.3) minutes and the mean
hospital stay was 15.8 (8.1) days. Liver function tests are same with the others
authors at day 1, 4 and 7 after operation with return to normal value after 1
week. CONCLUSION: In major liver resection, vascular clamping is not always
necessary.
PMID- 9638408
TI - Total vascular exclusion for liver resection.
PMID- 9638409
TI - Routine use of total hepatic vascular exclusion in major hepatectomy is not
necessary.
AB - The prime concert of a hepato-biliary surgeon undertaking liver resection is to
minimise blood loss and prevent air embolism through the control of the major
vascular structures. Several methods to achieve this are now available and
include in particular clamping of the hepatic pedicle and total vascular
exclusion. Both techniques are detailed as well as their benefits and drawbacks.
For conventional liver resections, total vascular exclusion has no advantage over
clamping of the hepatic pedicle in preventing blood loss and is associated with
additional morbidity. This technique should be selectively used in patients with
tumours involving major hepatic veins or the inferior vena cava.
PMID- 9638410
TI - Selective and unselective clamping in cirrhotic liver.
AB - BACKGROUND/AIMS: Liver surgery requires a reduction of the operative blood loss
especially for patients with cirrhosis. Selective or unselective liver clamping
during hepatic resection is performed to minimize the surgical risk for such
compromised patients. METHODOLOGY: We carried out elective hepatic resection in
158 patients with the use of total hilar clamping (Pringle's manoeuvre) or
selective vascular clamping (Makuuchi's manoeuvre). The clinical outcomes were
evaluated according to the clamping method and the condition of background liver.
RESULTS: Pringle's manoeuvre was used in 132 patients who underwent all types of
hepatectomy, whereas Makuuchi's manoeuvre was applied selectively to 26 patients,
most of whom underwent segmentectomy or subsegmentectomy. A modified Makuuchi's
manoeuvre was used in eight healthy donors who underwent left-sided hepatectomy
for transplantation. The cumulative clamping times and blood losses were 61 +/-
47 min (mean +/- SD) and 831 +/- 716 ml in the Pringle's manoeuvre group, and 95
+/- 47 min and 1.035 +/- 577 ml in the Makuuchi's manoeuvre group. In patients
with normal hepatic parenchyma the longest clamping time was 322 min, and in
those with cirrhosis it was 202 min. All the patients in this series tolerated
vascular clamping well, and their hepatic functional parameters returned,
regardless of the presence or absence of cirrhosis, to the baseline levels within
a week. As a whole, the operative morbidity and mortality rates were 20.3% and
0%, respectively. CONCLUSIONS: Intermittent total or selective clamping can be an
indispensable procedure during hepatic resection for all patients, irrespective
of the degree of hepatic dysfunction, to improve safety and resectability.
PMID- 9638411
TI - Hepatectomy with hypothermic perfusion of the liver.
AB - Whereas most liver resections can be performed within 60 min, the period of
vascular clamping and resulting ischemia may prove too short to allow complex
major liver resections (MLR) especially on diseased livers. To overcome this
problem, cooling of the liver with 4 degrees C preservations solution routinely
used in liver transplantation may be used in three different approaches to MLR: I
"In situ": the liver remains in the abdomen and integrity of afferent and
efferent vessels is conserved. II "Ex situ-in vivo": the liver exteriorized from
the abdomen by transecting all hepatic veins, remains connected to the porta
hepatis. III "Ex vivo": the liver being removed from the abdomen, the MLR is
performed extracorporeally. Of 15 MLR reported here, 11 were performed "in situ"
and 4 "ex situ-in vivo"/Nowadays, the liver surgeon's "toolbox" must contain
hypothermic liver perfusion. In carefully selected cases, these techniques allow
MLR on diseases livers or mandating complex vascular procedures.
PMID- 9638412
TI - Intermittent complete vascular exclusion of the liver during hepatectomy:
technique and indications.
AB - BACKGROUND/AIMS: Complete intermittent vascular exclusion of the liver (IVEL)
combines clamping of the hepatic pedicle with clamping of the hepatic veins
without interruption of the caval flow. The major advantages of this technique
are that patient preclamping fluid overload is avoided, major haemodynamic
changes due to caval clamping are escaped, and it allows a very long clamping
time. Disadvantage of this technique is the necessity of looping the terminal
part of the hepatic veins. METHODOLOGY: In this prospective study, 41 cases of
IVEL (Representing 19% of the hepatectomies carried out for cancer during the
same period) used for difficult hepatectomies were analyzed, and the operative
technique is presented. RESULTS: IVEL was feasible in 90% of the 46 attempted
cases, and completely controlled the bleeding in 90% of the cases. The mean
duration of IVEL was 69.2 minutes (Range: 37 to 140), and was greater than 130
minutes in three patients. No liver failure occurred during the postoperative
course. CONCLUSION: We conclude that IVEL without caval clamping is a new, and
valuable, technique of vascular exclusion of the liver. Its application is
indicated in the following conditions: 1. For patients who should have classical
vascular exclusion but cannot tolerate vena cava clamping (18% of the cases), 2.
for patients with pathological liver parenchyma when intrahepatic venous pressure
is high, 3. for patients with impaired liver parenchyma, requiring conservative
surgery that leads to anatomic or non-anatomic resection close to a vein
(Example: A tumor located in the dihedral angle of the terminal part of two
hepatic veins), 4. for patients with tumors closely located to a hepatic vein
that must be preserved and sharply dissected (Example: A left trisegmentectomy
that requires pelting of the right hepatic vein), and 5. for the scarce patient
with tumors infiltrating the major hepatic veins, constraining a hepatic vein
reconstruction to preserve liver function.
PMID- 9638413
TI - Pancreatic resection for pancreatic carcinoma combined with neo- and adjuvant
locoregional targeting immuno-chemotherapy--a prospective randomized study.
AB - BACKGROUND/AIMS: The effects on early and late results of combined pancreatic
resection with neo- and adjuvant immuno-chemotherapy for patients undergoing
pancreatic resection are prospectively evaluated. METHODOLOGY: A group of 26
patients was divided into two groups, which were matched in terms of age-sex
ratio, stage of disease, histological diagnosis and mode of pancreatic resection.
Group A patients received a multimodality therapy, combining pancreatic resection
with neo- and adjuvant locoregional targeting immunochemotherapy. Group B
received pancreatic surgery only. RESULTS: For Group A patients (n = 14pts), a
complete response was seen in 11 patients with a time interval ranging from 9 to
29 months. In the remaining 3 patients liver secondaries developed 12 months
after pancreatic resection in 2 patients and the other patient developed
pulmonary metastases 22 months after pancreatic resection. All patients (n =
3pts) are alive, but continue to have the disease. For Group B patients (n =
12pts), a complete response was seen in 3 patients with a survival of 9, 10 and
20 months following pancreatic resection. Six patients died due to locoregional
recurrence of the disease, with the survival rate ranging from 7 to 18 months
(mean 10 months). Locoregional recurrence was complicated with liver secondaries
(n = 3) and with peritoneal dissemination of the disease in a further 3 patients.
The remaining 3 patients are alive, but continue to have the disease due to
locoregional recurrence. CONCLUSIONS: Patients in whom neo- and adjuvant
locoregional immunochemotherapy was carried out in conjunction with pancreatic
resection, demonstrated a significantly higher response rate to treatment.
Therefore the data collected offers clear evidence, regarding the usefulness,
applicability and safety of combined neo- and adjuvant therapy with pancreatic
resection. A Multi-modality approach is therefore highly recommended.
PMID- 9638414
TI - Intrasplenic immunostimulation in malignancies fact or fiction? Present and
future.
AB - BACKGROUND/AIMS: The clinical application of intrasplenic immunostimulation with
IL-2 in a group of patients suffering from metastatic renal carcinoma, melanoma,
recurrent rectal carcinoma, lung carcinoma and gastric carcinoma are discussed in
terms of clinical applicability, effectiveness and survival. METHODOLOGY: From
May 1996 to February 1998, 45 patients with advanced malignancies were admitted
to Athens Medical Center for intrasplenic immunostimulation. Transplenic
immunostimulation was carried out via a subcutaneously implanted port. The
injected therapy included IL-2 (Proleukin) 1 ml 18 x 10(6) suspended in 1.5 ml of
lipiodol and 0.5 ml of urografin. In conjunction gamma-INF (Immukin) 0.5 ml 100
mcg, was administered. RESULTS: Patients included in this study have completed
their treatment, or are still undergoing maintenance treatment. The duration of
the CR was between 11 and 16 months, and for PR was between 10-14 months. For
melanoma patients (n = 9), 3 patients with PD died 9, 10 and 12 months after
initial treatment began. The remaining patients (n = 6) are alive with a mean
survival rate of 16 months. Of those patients, 4 have been classified as complete
responders, being completely free of disease at this time. The number of CR for
patients with lung, renal and recurrent rectal cancer was achieved as a result of
the continuing maintenance treatment. Twenty-two patients remain alive and 23
patients have died. From those alive (n = 22), 10 patients are complete
responders and free of disease, 10 are partial responders with controlled disease
and 2 remain with standard disease. For those surviving patients with lung
cancer, the mean survival time is 14 months. Patients with recurrent rectal
cancer and renal cancer were shown to have a mean survival time of 15 and 13
months, respectively. CONCLUSION: The safety, effectiveness and feasibility of
long-lasting administration of high dosages of IL-2 are documented from the data
of this study. Intrasplenic immunostimulation utilizing lipiodol-urografin
emulsion as a carrier, offers new possibilities for the safe administration of
long lasting high dosages of IL-2 and gamma-INF. Further studies are warranted,
to further elucidate the results of this phenomenon.
PMID- 9638415
TI - Diphenylhydantoin-induced hepatitis: a case report.
AB - This case report is of a 25-year old man with severe diphenylhydantoin-induced
hepatitis, fever, rash and generalized lymphadenopathy. Hepatic histology and
lymphocyte transformation tests strongly supported the diagnosis. He made an
uneventful recovery with supportive therapy.
PMID- 9638416
TI - Endoscopic irradiation and parallel arrangement of Wallstents for hilar
cholangiocarcinoma.
AB - BACKGROUND/AIMS: The placement of two Wallstents in parallel seems to be a common
solution for endoscopic technique in order to obtain bilateral hepatic drainage
in patients with hilar biliary strictures. However, a biliary stricture at the
hepatic confluence hinders the sequential delivery of multiple Wallstents.
Intraductal irradiation has been shown to recanalize the cancerous stricture
caused by cholangiocarcinoma. METHODOLOGY: We attempted to place two Wallstents
in parallel by endoscopic means after endoscopic intraductal irradiation with a
high-dose rate afterloading device in three patients with hilar
cholangiocarcinoma. After the placement of two guidewires into the bilateral
hepatic ducts, two Wallstents were sequentially delivered over the guidewires.
RESULTS: Owing to adequate re-opening of the hilar bile ducts after irradiation,
the delivery of the second Wallstent alongside the expanded first Wallstent could
be readily accomplished in all of the patients without complications. Two
Wallstents were placed so that their distal ends were juxtaposed in the common
bile duct, ensuring good drainage. There were no signs of recurrent biliary
obstruction in any of the patients during the follow-up period of 24 to 44 weeks.
CONCLUSION: This endoscopic technique seems to be simple, safe, and reliable in
obtaining bilateral hepatic drainage with Wallstents in patients with hilar
cholangiocarcinoma.
PMID- 9638417
TI - Effect of long-acting somatostatin analogue (octreotide, SMS 201-995) plus
calcium channel blocker (verapamil) on gallbladder contraction.
AB - BACKGROUND/AIMS: In this study we investigated the effect of the long-acting
somatostatin analog octreotide (SMS 201-995) plus calcium channel blocker
(Verapamil) on gallbladder contraction. METHODOLOGY: Fourty healthy volunteers
participated in this study. Gallbladder volumes were measured by ultrasonography.
After recording the baseline measurement, the volunteers received either saline
(n:10), or SMS 201-995 100 B microgram subcutaneously (s.c.) (n:10) or verapamil
80 mg peroral (po) (n:10), or verapamil plus SMS 201-995 (n:10). Two hours later
the gallbladder volumes were rescanned in 15 min intervals for 60 min. At the end
all volunteers received standard liquid test meal (ensure 250 Cal/250 ml) and
scans were again performed for one hour. RESULTS: The mean baseline gallbladder
volume was 18.6 +/- 5.2 ml in all groups. The gallbladder volumes in the placebo
group were 18.6 +/- 5.2 to 19.0 +/- 10.2 ml. In this group, after administration
of test meal decreased the mean gallbladder volume to 14.3 +/- 7.5 to 8.4 +/- 5.8
ml, but these values were not significantly different from the baseline values.
In the verapamil group the volumes increased from 18.6 +/- 5.2 to 28.5 +/- 9.7 to
30.8 +/- 11.6 ml. These values were significantly different from the baseline and
the control group (p < 0.05). In this group, post-prandial mean volumes decreased
to baseline in 30 min, but these values were higher than in the placebo group (p
< 0.01). Verapamil-induced fasting the gallbladder relaxation was totally
abolished to the placebo value by SMS 201-995. In verapamil plus SMS 201-995 and
SMS 201-995 alone groups, the fasting and post-prandial volumes did not change
when compared to the baseline value, but post-prandial volumes were higher than
the placebo (p < 0.01). CONCLUSION: These results suggest that verapamil-induced
gallbladder relaxation was totally abolished by SMS 201-995.
PMID- 9638418
TI - A traumatic neuroma associated with obstructive jaundice after laparoscopic
cholecystectomy.
AB - A traumatic neuroma of the biliary tract is rarely associated with biliary
obstruction. The authors describe a case of obstructive jaundice that occurred
after laparoscopic cholecystectomy. Obstructive jaundice developed in a 39-year
old woman 8 months after laparoscopic cholecystectomy. The stricture was resected
and a Rouxen-Y hepaticojejunostomy was performed. Histological examination
revealed a traumatic neuroma and a fibrous scar around the biliary duct. To our
knowledge, a traumatic neuroma of the biliary tract after laparoscopic
cholecystectomy has not been reported previously. Thermal injury may cause the
late onset of a fibrous scar and traumatic neuroma. Therefore, traumatic neuroma
should be included in the differential diagnosis when late-onset biliary tract
obstruction develops after laparoscopic cholecystectomy.
PMID- 9638419
TI - A case of early cancer in cystic intrahepatic duct associated with congenital
choledochal cyst.
AB - Herein, we report an extremely rare case of early cancer localized in the cystic
intrahepatic duct, which is associated with the choledochal cyst including both
the intra- and extrahepatic duct (type IV-A cyst). A small polypoid lesion in the
cyst was detected by computed tomography. Extensive resection of the choledochal
cyst with lobectomy was performed on the tumor in a 23-year-old woman. Tubular
adenocarcinoma localized in the wall of the cystic left hepatic duct was
histologically confirmed. Awareness of the diagnostic and treatment modalities,
with a focus on potential malignancy in the cystic intrahepatic duct, in cases
with anomalous arrangement of the pancreatobiliary duct is necessary.
PMID- 9638420
TI - Correlation of macroscopic and histological characteristics in the regional lymph
nodes of patients with rectal and sigmoidal adenocarcinoma.
AB - BACKGROUND/AIMS: The number of involved lymph nodes is a relevant prognostic
parameter which determines the duration of survival in patients with colonic and
rectal adenocarcinoma. The purpose of this study was to establish a correlation
between the macroscopic (size and consistency) and microscopic characteristics of
the regional lymph nodes (type of involvement in tumor tissue, state of the
capsule, adherence of the lymph nodes, etc.) in patients with colorectal
carcinoma. METHODOLOGY: In this prospective study, 46 patients with rectal and
sigmoid adenocarcinoma were studied through randomized selection. From the
resected specimens, a total of 736 lymph nodes were identified (average 15.66 per
patient), with the precise location determined according to Enker and
Philiphsken. The macroscopic and microscopic characteristics of each lymph node
were identified. These lymph node findings were then distributed by means of the
x2 test, while the interrelationship of lymph node characteristics was determined
by factor analysis. RESULTS: Within the group of "small" lymph nodes, 17.18% were
malignant. Additionally, of all the malignant lymph nodes, 46.23% were less than
5 mm in diameter. Although the malignant lymph nodes were predominantly diffusely
involved within the tumor tissue, 19.50% were focally involved within the tumor
tissue, of which 48.38% were "small" lymph nodes, which are commonly non
palpable. Perforation of the capsule and adherence were more characteristic for
focally mutated than for diffusely mutated lymph nodes in the cases of
malignantly mutated lymph nodes. CONCLUSION: Size and consistency of the lymph
nodes are not dependable parameters for appraisal of lymph node involvement in
tumor tissue, the state of the lymph node capsule, nor the interrelation among
the lymph nodes. As in the case of the primary tumor, local tumor aggression in
the lymph nodes is conditioned by the grade of differentiation, i.e. histologic
immaturity, rather than by tumor size.
PMID- 9638421
TI - Discriminant analysis of pre- and intraoperatively detected prognostic factors
influencing lymph node involvement in patients with colorectal carcinoma.
AB - BACKGROUND/AIMS: The aim of this study was to establish whether, and to what
extent, pre- and intraoperatively detected characteristics (demographic,
anamnestic and laboratory data) and tumor characteristics can be used in the
assessment of regional lymph node involvement in patients with colorectal
carcinoma. The assessment also included the number of lymph nodes involved in
patients with positive lymph nodes. Considering that the number of obtained lymph
nodes widely varies in resected specimens, assessment parameters also included
the percentage of the involved lymph nodes within the total population of lymph
nodes. METHODOLOGY: From 1992-1993, 46 patients with carcinoma of the rectum and
sigmoid colon were studied, with a total number of 736 lymph nodes evaluated. Out
of the total number of lymph nodes, 577 (78.4%) were benign and 159 (21.6%),
malignant. Data were analyzed by multi-variant statistical methods, namely:
discriminant analysis and multiple regression with the aid of SPSS/PC+ software.
RESULTS: For this patient group, we evaluated the following potentially
predictive factors for lymph node involvement: age; serum hemoglobin, albumin and
alkaline phosphatase levels; weight loss; and the primary tumor localization
characteristics: histologic type, macroscopic growth pattern and depth of tumor
invasion of the bowel wall. We found that there was no difference in the
prediction of regional lymph node involvement between analysis of the
aforementioned parameters and analysis of the isolated discriminators only.
CONCLUSION: A predictability likelihood of 83.78% greatly surpasses the
acceptable error tolerance level of 5%. Correlation of demographic, anamnestic
and laboratory data about the patient and the characteristics of the primary
tumor cannot be used in distinguishing malignant lymph nodes from benign ones.
These data cannot be the basis for exact intraoperative staging and thus cannot
be significant criteria for decision-making about operative treatment modalities.
PMID- 9638422
TI - Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel
disease.
AB - BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors
in inflammatory bowel disease, particularly Crohn's disease. The aim of our study
was to assess rectal blood flow in patients with active inflammatory bowel
disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood
flow was performed by laser Doppler flowmetry in 45 subjects divided into three
groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS:
Rectal perfusion was found to be significantly impaired in patients with
ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our
results confirm the role of local ischemia in ulcerative colitis, but do not
support the theory that vascular factors play a key role in the pathogenesis of
Crohn's disease.
PMID- 9638423
TI - Diagnostic and treatment of Zenker's diverticulum: review of our series pharyngo
esophageal diverticula.
AB - BACKGROUND/AIMS: Clinical aspects and preneoplastic potential of Zenker's
diverticulum justify its surgery. The clinical signs of the patients and the size
of the diverticulum determine the surgical technique. METHODOLOGY: Between
January 1974 and December 1995, 32 patients underwent surgery in our department.
In order to compare the surgical technique, we divided the patients into 3
groups: group A (cricopharyngeus myotomy: 15 patients (46.9%)), group B (myotomy
with diverticulectomy: 15 patients (46.9%)) and group C (myotomy with
diverticulopexy: 2 patients (6.7%)). The chi-square test was used for statistical
analysis, p < 0.05. RESULTS: Local or regional anaesthesia was used in 7 patients
from group A (46.6%); 5 patients from group B (33.3%) and all the patients from
group C (100%). General anaesthesia was used in 8 patients from group A (53.4%),
10 patients from group B (66.7%) and 0 patients from group C (0%). The overall
mortality was 0%. The mean postoperative stay in group A was 6 +/- 2 days (3-10
days); in group B was 11.6 +/- 6.4 days (5-25 days) and in group C was 3.5 +/-
0.7 days (3-4 days). The mean postoperative stay in patients with local or
regional anaesthesia was 5.3 +/- 1.6 days (3-9 days) and in patients with general
anaesthesia, 10.9 +/- 6.1 days (4-25 days). No statistically significant
difference was found between the anaesthetic technique and the surgical technique
(p = 0.193), between the surgical technique and the mean postoperative stay (p =
0.596) and between the anaesthetic technique and the mean postoperative stay (p =
0.166). CONCLUSIONS: Cricopharyngeus myotomy is the main surgical technique,
however, in diverticula longer than 3 cm of diameter it is mandatory to associate
diverticulectomy. Diverticulopexy is indicated in patients of advanced age with a
high surgical risk. Local or regional anaesthesia facilitates the identification
of the diverticulum intraoperatively and reduce the mean postoperative stay,
however, there is no statistical significant difference.
PMID- 9638424
TI - Carcinoid somatostatinoma of the papilla of Vater: a case report.
AB - A 57 year-old Japanese man with a carcinoid somatostatinoma of the papilla of
Vater is presented. He was found to have cholecystolithiasis without any
symptoms. Physical examination showed no abnormal findings. Routine laboratory
data gave normal results, except for glucose intolerance and an elevated
somatostatin concentration. A yellowish papillary tumor was found at the papilla
of Vater, and histological examination suggested the diagnosis of carcinoid. He
underwent a pancreatoduodenectomy in March 1992. The gallbladder contained a
single pure cholesterol stone. Histological, immunohistochemical, and electron
microscopic studies resulted in the diagnosis of a carcinoid somatostatinoma of
the papilla of Vater, without regional lymph node metastases. Post-operative
pancreatic juice output from the total pancreatic duct drainage increased to more
than 1000 mL/day. Although an anastomotic leakage of the pancreatojejunostomy was
noted, the pancreatic fistula closed 8 weeks later. His postoperative
somatostatin value was normal. He has been well for 54 months following surgery,
without any signs of recurrence.
PMID- 9638425
TI - Intussusception of the small bowel due to Peutz-Jeghers syndrome: a case report.
AB - We report the case of a 45-year-old woman with an intussusception of the small
bowel due to Peutz-Jeghers syndrome. Immediate laparotomy was performed, and
approximately 5 cm of the small bowel had to be removed because of ischemic
areas. Six other polyps were removed through buttonhole enterotomies. The Peutz
Jeghers syndrome is rare. Treatment is either surgery or a combination of surgery
and intraoperative enteroscopy. Bowel resections must be kept to a minimum.
PMID- 9638426
TI - Mesenteric neurofibroma with von Recklinghausen's disease: a case report.
AB - Mesenteric neurofibroma associated with von Recklinghausen's disease is rare.
Herein, we present one such case. A 15-year-old mentally retarded Japanese boy
presented with destruction of the right 2nd and 3rd ribs on a routine chest
roentgenogram. Physical examination revealed a funnel chest and multiple cafe-au
lait spots, but no cutaneous nodules. Although the patient had no symptoms, a
computed tomography (CT) and angiogram were performed. There were no definitive
findings of malignancy in the tumors. However, since there were two risk factors
for malignancy, specifically, a young age at the time of diagnosis and multiple
tumors, and coupled with the size of the abdominal tumor which was large, the
abdominal mesenteric tumor was removed. Pathological examination showed a
neurofibroma with no evidence of malignancy.
PMID- 9638427
TI - Infantile hemangioendothelioma with a highly elevated serum alpha-fetoprotein
level.
AB - Infantile hemangioendothelioma is the most common vascular tumor in infancy. A
three-month-old infant was admitted to the hospital for hepatomegaly. Abdominal
ultrasonography, a CT-scan, and MRI studies demonstrated bilateral diffuse
hepatic nodules, which were characteristic of hepatic hemangioendothelioma. A
highly elevated alpha-fetoprotein (AFP) level misled us to an impression of
hepatoblastoma, but the pathology report through an open biopsy disclosed a liver
hemangioendothelioma. The patient responded to methylprednisolone therapy. A
follow-up sonogram revealed regression of the hepatic masses. This case
emphasizes that an elevated AFP level of up to 400 ng/ml is normally found in
some neonates until two months of age. Careful interpretation of this value is
very important, especially when it is associated with a hepatic tumor. Herein, we
present a case of infantile hemangioendothelioma in a three-month-old boy with a
highly elevated serum AFP.
PMID- 9638428
TI - Carcinoembryonic antigen and intra-arterial chemotherapy response of liver
metastases.
AB - BACKGROUND/AIMS: We investigated the relationship between serum carcinoembryonic
antigen and response to hepatic artery chemotherapy for unresectable colorectal
liver metastases. METHODOLOGY: The study included 14 patients with unresectable
colorectal liver metastases receiving hepatic arterial chemotherapy weekly.
Patients were evaluated monthly including liver function tests and
carcinoembryonic antigen. Ten patients received high dose 5-fluorouracil (1000
mg/m2) and 4 patients received other regimens. One patient underwent hepatectomy
for cure after 5-fluorouracil. RESULTS: Thirteen patients (93%) had normal
quality of life without toxicity during hepatic artery infusion. Response rate in
the high dose 5-fluorouracil group was 50%, while the response rate of other
regimens was 25%. Mean survival time differed between responding (n = 6) and non
responding patients (n = 8) (527 vs 289 days), and the high dose 5-fluorouracil
(n = 10) and other regimens (n = 4) (462 vs 213 days). In responding patients,
peak serum carcinoembryonic antigen levels before hepatic artery infusion
decreased within 6 months. In the non-responding patients, serum carcinoembryonic
antigen levels increased rapidly despite hepatic artery infusion. CONCLUSIONS:
Serum carcinoembryonic antigen levels correlated well with response. Hepatic
artery infusional chemotherapy with high dose 5-fluorouracil may be recommended
as effective treatment for unresectable liver metastasis from colorectal cancer
if serum carcinoembryonic antigen levels decrease within 6 months.
PMID- 9638429
TI - Glucagon and insulin metabolism in cirrhotic patients.
AB - BACKGROUND/AIMS: The aim of this study was to investigate glucagon and insulin
metabolism in order to clarify the mechanisms that lead to hyperglucagonemia and
hyperinsulinemia in cirrhosis. METHODOLOGY: Splanchnic output and metabolic
clearance rates were studied in 16 cirrhotic patients and 5 non-cirrhotic
controls. Splanchnic glucagon and insulin output into the portal circulation were
calculated by the difference between portal venous and systemic arterial
concentration multiplied by portal plasma flow. The metabolic clearance rate was
calculated as the ratio of output to systemic arterial concentration. Portal
blood flow was measured by continuous local thermodilution. RESULTS: Arterial
glucagon levels were higher in cirrhotics than in controls. Glucagon output was
triple of that found in controls (52.4 +/- 7.0 vs 17.7 +/- 2.9 ng/min, p < 0.05).
Both groups exhibited similar metabolic clearance rates of glucagon. Systemic
arterial insulin values were higher in cirrhotics than in non-cirrhotics. Insulin
output was not significantly different between the two groups. However, metabolic
clearance of insulin in cirrhotics was reduced to one half of the rate found in
controls (237.0 +/- 39.8 vs. 450.5 +/- 17.5 mL/min, p < 0.05). CONCLUSIONS:
Hyperglucagonemia in cirrhotic patients results from increased pancreatic output,
while hyperinsulinemia results from decreased insulin clearance.
PMID- 9638430
TI - Determination of hepatic zinc content in chronic liver disease due to hepatitis B
virus.
AB - BACKGROUND/AIMS: Zinc is an essential, mostly intracellular, trace element which
participates in many physiologic mechanisms. Some liver functions like urea
formation require the presence of zinc; thus the determination of hepatic zinc
content may contribute to the understanding of probable zinc-related clinical
consequences of chronic liver disease. In this study, we aimed to determine the
hepatic zinc concentrations in patients with chronic liver disease due to the
Hepatitis B virus and to ascertain the relationship between the severity of liver
disease and hepatic zinc content, if one in fact exists. METHODOLOGY: A total of
99 HBsAg positive subjects were included in the study. We performed a liver
biopsy on all subjects. Hepatic zinc concentrations were determined by atomic
absorption spectrophotometry. RESULTS: The liver biopsies were normal in 25
subjects. There were 33 chronic active hepatitis (CAH), 34 cirrhosis and 7
chronic persistent hepatitis (CPH) patients in the study group. In the control
group, CAH, cirrhosis and CPH groups, the mean liver zinc concentrations were
3.83 +/- 1.86, 1.86 +/- 0.92, 1.14 +/- 0.68 and 3.74 +/- 1.81 mumol/g dry weight,
respectively. Hepatic zinc in the CAH and cirrhosis groups were lower than that
of the control group (p < 0.05). We also found that liver zinc in the cirrhosis
group was lower than in the CAH group (p < 0.05). CONCLUSION: According to these
results, as the severity of liver damage increases, the hepatic zinc
concentration decreases. Therefore, it can be suggested that zinc supplementation
may improve hepatic encephalopathy by increasing the efficiency of the urea
cycle.
PMID- 9638431
TI - Does hypothermic perfusion have beneficial effects for ischemic liver during
extended hepatectomy with hepatic inflow occlusion of canine liver? A comparative
study with topical cooling.
AB - BACKGROUND/AIMS: The present study was designed to elucidate the effect of
topical cooling and hypothermic perfusion in extended hepatectomy under hepatic
inflow occlusion. Hypothermic perfusion has provided to have a protective effect
on the ischemic liver. However, it has not been determined whether hypothermia or
perfusion had salutary effects on the ischemic liver. METHODOLOGY: Seventy-five
percent of the liver was resected under hepatic inflow occlusion for 60 minutes
in each adult mongrel dog. The animals were divided into three groups; no cooling
group (n = 8), topical cooling group (n = 7) using ice slush and hypothermic
perfusion group (n = 7). Blood from the hepatic vein was sampled for measurement
of ALT, AST, LDH and purine nucleoside phosphorylase. RESULTS: The seven-day
survival in topical cooling group and hypothermic perfusion group was better
compared with that in no cooling group. ALT, AST and LDH levels showed no
significant differences among the groups. PNP levels were significantly lower in
topical cooling group (p < 0.01) and hypothermic perfusion group (p < 0.05) than
in no cooling group, but no significant differences between topical cooling group
and hypothermic perfusion group. CONCLUSIONS: In the hepatic ischemia for 60
minutes, hypothermic perfusion did not demonstrate markedly better effects
compared with topical cooling.
PMID- 9638432
TI - Significance of the peroral phenolsulfonphthalein test in hepatic resection: a
possible predictor of bacterial translocation.
AB - BACKGROUND/AIMS: The aim of this study was to evaluate the perioperative changes
in intestinal permeability by using the phenolsulfonphthalein (PSP) test and to
also to clarify the significance of the peroral PSP test in hepatic resection.
METHODOLOGY: Fifty patients, all of whom underwent hepatic resection, were
prospectively studied. Postoperative complications occurred in 16 patients, and
10 of these complications were infectious. A peroral PSP test, which was
scheduled before operation and on postoperative days 3, 7, and 14, was performed
as follows: after the administration of 30 mg of PSP, a 24-hour urine was
collected, and the urinary PSP was measured by colorimetric assay. The
correlation between the preoperative PSP value and various clinical variables,
such as perioperative changes in urinary PSP excretion, and the relationship
between the postoperative PSP value and postoperative complications, were
investigated. RESULTS: Preoperative urinary PSP excretion was found to increase
in proportion to the degree of liver dysfunction. In contrast, urinary PSP
excretion did not significantly change during the perioperative period. However,
urinary PSP excretion on postoperative day 3 in patients with postoperative
infectious complications (27.3%) was significantly greater than that in those
without infectious complications (17.4%; p < 0.05). Furthermore, PSP excretion on
postoperative day 3 in those with infectious complications was also significantly
greater as compared to the preoperative level. The patients with a urinary PSP
excretion level on postoperative day 3 of greater than 25%, exhibited infectious
complications more frequently than patients with a level under 25% (60% versus
10.3%, respectively; p < 0.05). CONCLUSIONS: The peroral PSP test is thus
suggested to be a possible predictor of bacterial translocation after hepatic
resection.
PMID- 9638433
TI - Treatment of chronic hepatitis C genotype 4 with alpha-interferon in Saudi
Arabia: a multicenter study.
AB - BACKGROUND/AIM: Several studies have indicated that there are certain predictive
factors (gender, duration of infection with HCV, cirrhosis and genotype of HCV)
of a better response with alpha-interferon treatment in patients with chronic
hepatitis C. The aim of this study was to evaluate these factors in Saudis and
other Arab nationals with chronic hepatitis C-genotype 4-undergoing alpha
interferon treatment. METHODOLOGY: A multicenter study was conducted between 1992
and 1994 on 80 consecutive patients who were prospectively recruited and
randomized in treatment and control groups. RESULTS: The results of this
multicenter study indicated a low response rate to alpha-interferon with an
overall response rate of 43%, of which 28% was complete. The sustained response
was only 16%. Among the reasons for this low response in our study are the high
percentage of patients with cirrhosis and the long infection interval, as about
80% of our HCV cases were community-acquired. CONCLUSION: Liver cirrhosis was
found to be the main predetermining factor for response to interferon treatment.
Genotype 4 was not a contributing factor to the difference in response rate.
PMID- 9638434
TI - Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary
gastric cancer.
AB - BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric
cancer, it is usually presumed to be metastatic. However, this may not be true in
a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This
study was conducted to examine the clinicopathological factors of both
conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a
synchronous hepatectomy in combination with radical gastrectomy over the past 15
years was performed. RESULTS: Seven patients had metastatic gastric cancer, and
seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node
metastasis were the major features in the patients with metastatic gastric
cancer. Early gastric cancer was found in three of the patients with the
coexisting primary cancers. No patient with solitary metastatic cancer survived
more than one year, but long-term survival of more than two years was achieved in
two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the
stomach and liver should be kept in mind in patients with gastric cancer
concomitant with a solitary hepatic tumor, in order to provide optimal treatment.
PMID- 9638435
TI - Treatment of benign hepatic cysts by instillation of tetracycline hydrochloride.
AB - BACKGROUND/AIMS: Despite the high frequency of benign hepatic cysts, they rarely
cause symptoms. Large cysts, however, may produce clinical manifestations. In
these cases, ultrasonography-guided therapy has been proposed. We report the
results of this therapy in patients with symptomatic benign hepatic cysts.
METHODOLOGY: Seven patients with non-parasitic, non-neoplastic benign hepatic
cysts were submitted to fine-needle ultrasonography-guided aspiration, followed
by injection of diluted tetracycline hydrochloride (1 g). In all cases, cytology,
tumour markers and microbiology analysis of aspirates were performed. One patient
required two sessions. The grade of patient satisfaction and ultrasonography
changes were assessed 1, 3 and 6 months after the procedure. RESULTS: Cyst size
decreased in all patient, with total collapse in three. No major complications
occurred. Cytology, alpha fetoprotein, CA19.9, CEA and microbiology of the cyst
fluid confirmed the initial ultrasonographic diagnosis of simple biliary cysts.
Clinical complaints improved in 2 cases, and 5 patients became asymptomatic.
Ultrasonography evaluation 3 months after the procedure was more reliable in
predicting successful treatment. CONCLUSION: Intracystic instillation of
tetracycline hydrochloride is an effective and safe technique and may become the
first choice therapy for benign hepatic cysts.
PMID- 9638436
TI - Point mutations in the S and pre-S2 genes observed in two hepatitis B virus
carriers positive for antibody to hepatitis B surface antigen.
AB - Two hepatitis B virus (HBV) carriers who had antibodies to HBV surface antigen
(anti-HBs) were studied. Case 1 was a 47 year old woman positive for hepatitis B
e antigen (HBeAg), and case 2 was a 61 year old man positive for antibody to
HBeAg (anti-HBe) and DNA-polymerase (DNA-p). Neither case had received the HBV
vaccine. The nucleotide sequences of the HBV-DNA extracted from the patients'
sera were determined within the pre-S2 and S genes. Seven out of nine S gene
clones from case 1 and six out of nine S gene clones from case 2 had an amino
acid replacement from Thr or Ile to Ser at codon 126 in the alpha-determinant of
the S gene. Amino acid substitution of codon 145 of the S gene previously
reported was not observed. Although two previous reports on HBV escape mutant
carriers with both anti-HBs and HBeAg described some deletions in the pre-S2
gene, our cases did not show these deletions. Our analysis indicated that
carriers with the HBV escape mutant did not always have pre-S2 gene deletions. We
found two HBV escape mutant carriers who had amino acid substitutions at codon
126 in the S gene due to point mutation without any deletions in the pre-S2 gene.
PMID- 9638437
TI - Jejunal variceal bleeding after esophageal transection in a patient with
idiopathic portal hypertension.
AB - This report describes a 38-year-old man with massive gastrointestinal bleeding
from jejunal varices. He had been previously diagnosed to have idiopathic portal
hypertension and esophageal varices, and had undergone an esophageal transection
8 years earlier. The pre-operative diagnosis was a suspected hemorrhage from the
small intestine as visualized by 99mTc-HSAD scintigraphy (technetium 99m-labeled
human serum albumin D-type) and was not considered to be repeated massive lower
GI tract bleeding. An exploratory laparotomy was performed, and intra-operative
endoscopy revealed active bleeding from the jejunal varices. A partial resection
of the small intestine resulted in a complete resolution of the bleeding. A
review of the literature thereafter disclosed twelve previously reported cases of
jejunal variceal bleeding.
PMID- 9638438
TI - Left hepatic vein kinking after right trisegmentectomy: a potential cause of
postoperative liver failure.
AB - We report a case of left hepatic vein kinking which caused severe congestion of
the left lateral segment after right trisegmentectomy for a large liver tumor.
Intraoperative doppler ultrasonography documented an 80% reduction of the left
hepatic vein blood flow when the left lateral segment was rotated into the right
subphrenic space.
PMID- 9638439
TI - Graft mass and volume calculation in living related donors for liver
transplantation.
AB - Living related liver transplantation is one of the strategies currently used to
increase the donor pool. A preoperative and non-invasive estimate of the donor's
liver volume is needed to ensure sufficient functional liver reserve for survival
after resection, and to obtain a graft of adequate volume to suit the recipient's
features. A method based on a preoperative abdominal computerised axial
tomography of the donor, that enables the volume and mass of the whole liver, and
the graft, to be calculated is herein described. The compatibility of the
estimate with real graft mass after its removal has been proved, and the accuracy
of the calculi has been compared with other published methods. Moreover,
progressive growth of the recipient liver remnant has been demonstrated in
subsequent explorations.
PMID- 9638440
TI - Fibrolamellar hepatocellular carcinoma--an atypical MR manifestation.
AB - We report the imaging findings, specifically magnetic resonance pictures of a non
cirrhotic case of fibrolamellar hepatocellular carcinoma in an older patient (60
years). Computed tomography revealed non-enhanced hypodense central scar without
notable intratumoral calcification. MR imaging revealed a mass, which was
homogeneously hypointense on T1-weighted images (T1WI) and turned hyperintense on
T2-weighted images (T2WI). Stellate central scar was depicted with more
hypointensity on T1WI, however, it became markedly hyperintense on T2WI. This
manifestation is very different from the typical pattern reported in the
literature. In gadolinium enhanced T1WI, the mass other than the central scar got
enhanced. Fibronodular hyperplasia and fibrolamellar hepatocellular carcinoma
should be differentiated with reference to the clinical and imaging findings.
Collagenous central scar was described pathologically within the latter. However,
a discrepancy between the pathological and magnetic resonance pattern concerning
the central scar which was collagenous and corresponding to hyperintensity on
T2WI was found. To our knowledge no similar entity has been described in the
literatures so far.
PMID- 9638441
TI - Isoflurane hepatotoxicity in a patient with a previous history of halothane
induced hepatitis.
AB - Halogenated volatile anesthetics have been associated with liver injury. Most
reported cases have been linked to halothane and enflurane. Cross-sensitization
between the latter agents has also been documented. Isoflurane hepatitis is
extremely rare, and only a few convincing cases have been published. Moreover,
clinical cases of cross-sensitization of isoflurance with other haloalkanes have
not been reported. We describe a case of hepatic dysfunction 2 weeks after
isoflurance anesthesia in a 35-year-old obese woman with a previous history of
halothane hepatitis. The diagnosis was made on the basis of exposure to
isoflurance, the delay between the time of exposure and the onset of jaundice,
and the exclusion of other causes of liver dysfunction. This case reiterates the
recommendation that patients who sustain liver injury from one haloalkane should
not be exposed to another.
PMID- 9638442
TI - Separate histogenesis of combined hepatocellular and cholangiocellular carcinoma
in two patients.
AB - Double primary liver carcinomas, i.e. hepatocellular carcinoma (HCC) and
cholangiocellular carcinoma (CCC) are rare. Two patients in whom double primary
liver carcinomas were surgically resected are described herein. Case 1: A 51-year
old Japanese man with chronic type B hepatitis underwent hepatectomy for primary
HCC with intrahepatic metastasis. Case 2: A 67-year-old Japanese man with a
history of rectal cancer and CCC underwent lateral hepatic segmentectomy for a
suspected recurrence of intrahepatic CCC. Lack of direct contact between tumors,
no evidence of histological transition and clearly different immunohistochemical
staining for cytokeratin support a distinct histogenesis of the tumors in these
two patients. The findings indicate that combined HCC and CCC can arise
synchronously or metachronously as an intrahepatic double cancer.
PMID- 9638444
TI - Pancreatic head resection with segmental duodenectomy and preservation of the
gastroduodenal artery.
AB - BACKGROUND/AIMS: Duodenum-preserving pancreatic head resection has been performed
for benign pancreatic head diseases. Complete resection of the pancreatic head
with preservation of common bile duct and the duodenum sometimes causes common
bile duct or duodenal necrosis due to ischemia. We propose the simple, easy and
safe procedure for complete resection of pancreatic head with segmental
duodenectomy to prevent complications, which may be caused on duodenum preserving
pancreatic head resection. METHODOLOGY: Pancreatic head resection with segmental
duodenectomy including minor and major papilla was performed. By conserving the
right gastric artery, 5 to 7 cm of the first portion of the duodenum is preserved
with good arterial circulation. In addition, by conserving the anterior inferior
pancreaticoduodenal artery, the third portion and anal side of the second portion
of the duodenum are preserved with good arterial circulation. Resection of the
pancreatic head with 3 to 4 cm of segmental duodenectomy including minor and
major papilla completes this procedure. Reconstruction of the alimentary tract is
then performed with pancreatogastrostomy, end to end duodenoduodenostomy and end
to side choledochoduodenostomy. RESULTS: In 14 cases of pancreatic head diseases,
chiefly benign tumors, this procedure was successfully performed without severe
complications. Postoperative quality of life was quite satisfactory. CONCLUSION:
Using this procedure, complete resection of the pancreatic head for benign tumor
of the pancreatic head region can be performed safely and effectively.
PMID- 9638443
TI - Epithelial anomalies in chronic pancreatitis as a risk factor of pancreatic
cancer.
AB - BACKGROUND/AIMS: The relationship between chronic pancreatitis and the
development of pancreatic cancer is still a matter of dispute. Our aim was to
determine the frequency of hyperplastic, metaplastic and dysplastic epithelial
anomalies in the course of chronic pancreatitis and the potential steps in their
development to malignancy. METHODOLOGY: The study was based on biopsy material of
70 patients with clinically diagnosed advanced chronic pancreatitis, who
underwent partial or total pancreatectomy, as well as other operations. The
patients were assigned to 2 groups: Group I (n = 41) with calcifying chronic
pancreatitis; Group II (n = 29) with other forms of the disease. Histological
sections were stained with hematoxylin-eosin, Mallory-azan, Gomori's silver
method, and glycosaminoglycans (PAS and Alcian blue staining). Special interest
was focused on the type and incidence of epithelial ductal and acinar cell
anomalies, and on the degree of parenchymal scarring. RESULTS: Hyperplasia of the
ductal epithelium was present in 31.4%, focal squamous metaplasia in 21.4%,
mucous metaplasia in 11.1%, cellular dysplasia in 8.6%, dysplastic acinar cell
nodules in 21.4%, and "tubular complexes" in 30.0% of all cases. The differences
in the frequency of these changes, except for ductal epithelial hyperplasia, were
not statistically significant in two comparable groups. Advanced pancreatic
fibrosis was associated with epithelial anomalies in 65.7% of all cases.
CONCLUSIONS: From the morphological point of view, the adequate prerequisites for
the consideration of advanced forms of chronic pancreatitis, independent of type,
as a risk factor of pancreatic cancer exist, necessitating the surgical removal
of pathological lesions.
PMID- 9638445
TI - Factors predictive of the healing of pancreatic pseudocysts treated by
percutaneous evacuation.
AB - BACKGROUND/AIMS: Pseudocyst formation is a well-known complication of
pancreatitis which develops over 1 to 4 weeks in approximately 15% of patients.
Nearly one-third of pancreatic pseudocysts resolve spontaneously; however, if
there is no resolution within six weeks, evacuation must be performed. The aim of
this study was to prospectively assess the reliability of the following:
etiology; location; amount of pseudocyst liquid; and concentrations of certain
biochemical parameters (LDH, glucose, proteins, sodium, potassium, bilirubin,
lipase and amylase) in the pseudocyst content and patients' serum, in terms of
the efficacy of ultrasound-guided percutaneous evacuation as a therapeutic
approach. METHODOLOGY: Pseudocyst fluid was obtained by ultrasound-guided
percutaneous evacuation in 67 patients, with a history of pancreatitis and
pancreatic pseudocysts larger than five centimeters in diameter, with a matured
membraneous wall that persisted for more than six weeks. RESULTS: There is a
prognostic value associated with the location of the pseudocyst, the amount of
pseudocyst liquid and the concentration of proteins, potassium, lipase and
amylase in the evacuated material. CONCLUSION: Analysis of the aforementioned
parameters provides an early forecast of the outcome of percutaneous evacuation.
PMID- 9638446
TI - Solid cystic tumor of the head of the pancreas in a young woman.
AB - This a case report of a solid papillary tumor of the pancreas in a young woman of
18 years, who was referred to after having suffered for a period of 8 months with
a rather vague symptomatology, characterized by dyspepsia, fatigue and, towards
the end of the 8 month period, weight loss (approximately 2 kg). In the last
week, as a consequence of a modest abdominal trauma, the patient was submitted to
abdominal CT that showed a burden at the head of the pancreas, demonstrating a
round neoformation about 6 cm in diameter with solid echogenicity slightly
hypodense. Subsequently, she underwent an operation with the diagnosis of
pseudocystis of the pancreas. During surgery, a big cystic formation of the head
of the pancreas, into which a drain was introduced, was revealed. The
histological postoperative examination was compatible with pancreatic tumor with
a low grade of malignancy, cystic papillary or solid papillary type. Therefore,
the patient came under our observation and underwent an operation of
pancreatoduodenectomy. Two years after the operation, the patient had completely
recovered. In this case, we discussed the problem of performing certain
preoperative diagnoses despite the aid of modern diagnostic imaging, this being a
very rare illness that almost exclusively plagues young women (median age 19
years). This diagnosis has an uncertain histological origin and is generally
accompanied by a modest and vague symptomatology. The surgical procedure, given
the low grade of malignancy of the neoplasm and the excellent long-term
prognosis, must be, with respect to the oncological radicality, as conservative
as possible.
PMID- 9638447
TI - A new porto-systemic bypass technique for hepatopancreatoduodenectomy with portal
vein resection.
AB - When reconstructing the portal vein (PV) following hepatopancreatoduodenectomy
(HPD) with PV resection, a new porto-systemic bypass (PSB) technique can be
employed to prevent intestinal vascular congestion. The Whipple procedure is
performed in a standard manner, as long a portion of the gastrocolic trunk is
preserved for insertion of an antithrombogenic catheter (ATC). After harvesting
the left external iliac vein and exposing the right great saphenous vein, the end
of the ATC is inserted in the superior mesenteric vein via the gastrocolic trunk
in the distal direction and the other end of the ATC is inserted in the greater
saphenous vein. PSB is achieved as a result of the venous pressure gradient. By
employing this technique, an ATC can be inserted without damaging another
mesenteric venous branch and with minimal damage to the endothelium, and the
small intestine is not exposed in the operative field until enteric
reconstruction is started. This technique is a promising option for PSB during
HPD with PV resection.
PMID- 9638448
TI - Tyrosine hydroxilase activity in discrete brain regions from prehepatic portal
hypertensive rats.
AB - BACKGROUND/AIMS: Portal hypertension in patients and rat models are characterized
by splanchnic and systemic hemodynamic alterations. Both the central and
autonomic nervous systems are implicated in its pathophysiology. The aim of our
research was to study the tyrosine hydroxylase activity and the rate limiting
step in the biosynthesis of catecholamines in partial ligated portal hypertensive
and in control rat brains. METHODOLOGY: The following seven discrete brain
regions were investigated: Subfornical Organ, Organum Vasculosum Lamina
Terminalis, Median Eminence, Periventricular Nucleus, Area Postrema, Locus
Coeruleus and Nucleus Tractus Solitarius. RESULTS: The enzyme activity showed a
significant increment in six nuclei and a decrease in Area Postrema Nucleus when
portal hypertensive rats were compared to controls. CONCLUSIONS: These results
suggest the participation of some discrete brain regions in the mechanism of
hepatic portal hypertension under the present rat model.
PMID- 9638449
TI - Metallic stents for low invasive recanalization of the portal veins with
cancerous invasion--first case report.
AB - BACKGROUND/AIMS: Portal venous stenosis caused by cancer invasion has been
difficult to treat and patients do not have any treatment options. On the other
hand, protal venous stents have been applied to patients with variceal
haemorrhaging associated with portal vein thrombosis. However, there have not
been any reports concerning portal venous stents for malignant portal stenosis.
The aim of this report was to apply metallic stent for malignant portal stenosis
to reduce portal hypertension and restore portal venous blood flow, which in turn
leads to the recovery of liver function. METHODOLOGY: Two patients with portal
hypertension caused by malignant portal stenosis were treated by metallic stent
implantation. In one case, the stent was applied intraoperatively via the ileal
vein and in the other case, it was applied postoperatively via transhepatic
portal cannulation. RESULTS: In the first case, portal pressure monitored before
and after placement of the stent was 350 mmH2O and 200 mmH2O, respectively. Liver
function tests showed normalization after stent placement. In the second case,
over 3000 ml of ascites, which were drained through the drainage catheter every
day, could be reduced remarkably, and one week later, the catheter could be
withdrawn. Portal pressure before and after embedding the stent was 410 and 275
mmH2O, respectively. Both patients were discharged from the hospital and their
recovery was uneventfully. CONCLUSION: Both cases had an uneventful postoperative
course, with normalization of liver function and cessation of ascites on the next
postoperative day in case 2. Thus, portal venous stent should be considered a
viable option for the treatment of malignant portal stenosis.
PMID- 9638450
TI - Laparoscopic splenectomy with the newly devised morcellator.
AB - BACKGROUND/AIMS: One of the major hurdles to overcome in the development of
laparoscopic surgery has been finding effective extraction techniques for the
removal of large tissue masses. The electromechanical morcellator makes it easy
to remove relatively large sections of tissue from the abdomen through the
existing incisions. To determine the safety and efficacy of the new morcellator
in laparoscopic splenectomy, our preliminary experiences using the morcellator
were reviewed and retrospectively compared with the results in patients who
previously underwent conventional extraction techniques. METHODOLOGY: From
February 1992 to March 1996, 31 patients underwent laparoscopic splenectomy. In
the last eight patients, the new morcellator was used to remove the spleen, while
in the remaining 23 patients, a laparoscopic splenectomy was performed using the
conventional extraction techniques. RESULTS: In the last eight patients who
underwent laparoscopic splenectomy, the newly devised morcellator was
successfully used without any complications. The spleen could be removed from the
abdominal cavity in an average of 15.9 +/- 10.4 minutes using the morcellator,
while the average was 45.7 +/- 15.4 minutes using conventional techniques. It was
not necessary to extend the skin incision in patients with the morcellator,
while, on the other hand, a 2-cm extension of the existing skin incision was
always required to remove the spleen in the latter method. CONCLUSION: The
morcellator was found to be an effective device which can safely, efficiently and
rapidly remove tissue masses. This procedure is therefore considered to be one
feasible way to solve the age-old problem of intracorporeal morcellation.
PMID- 9638451
TI - Jejunal pouch with nerve preservation and interposition after total gastrectomy.
AB - BACKGROUND/AIMS: In this paper, we describe operative technique details and our
results with a modified technique for jejunal pouch formation and interposition
after total gastrectomy, with an overall aim to achieve results superior to
jejunal pouch and Roux-en-Y reconstruction, as reported in the literature.
METHODOLOGY: Following total gastrectomy, the jejunum was divided approximately
20 cm distal to the ligament of Treitz. Marginal vessels were not divided in
order to preserve the nerves in the 50 cm of distal jejunum which would be used
for pouch construction. The pouch was constructed using a linear stapler (Endo
GiA, United States Surgical Corp., Norwalk, Conn). A total of 15 gastric cancer
patients underwent construction of a nerve-preserving jejunal pouch and
interposition following total gastrectomy. RESULTS: None of the patients
experienced postoperative complications due to pouch construction. Additionally,
discomforts such as dumping or stagnation were not observed. Mild reflux
esophagitis occurred in five of the 15 patients and was resolved by oral
administration of camostat mesilate. Six months after surgery, the average
patient's diet volume and body weight had gradually increased to 79% and 86%,
respectively, of the presurgical levels. A dual phase, dual isotope radionucleid
pouch emptying study was also performed six months after surgery. The intra-pouch
RI retention rate was 47% for liquid food and 53% for solid food 120 minutes
after intake. The emptying rate was slower for both solid and liquid food, as
compared with healthy individuals. CONCLUSIONS: The pouch-emptying test
demonstrated a satisfactory retention capacity and an acceptable emptying time as
a gastric substitute. The patients who underwent gastric reconstruction with a
nerve-preserving jejunal pouch with interposition have experienced a reasonably
good quality of life.
PMID- 9638452
TI - The incidentally found leiomyoma that was in a resected stomach and its follow
up.
AB - BACKGROUND/AIMS: A prospective study measured the occurrence of leiomyoma in
patients receiving various gastric surgeries and the probable characteristics of
patients presenting an incidental leiomyoma. METHODOLOGY: Twenty-eight (3.5%)
patients with gastric leiomyoma were encountered among 796 resected stomach
specimens within the past two years. Of these patients, 11 exhibiting a
submucosal tumor were preoperatively diagnosed with endoscopy, whereas 17 showing
leiomyoma were incidentally found during a thorough survey of the resected
stomach specimens. Their demographic characteristics were compared. RESULTS:
Occurrence of incidental leiomyoma tended to be more common in patients with
gastric cancer than in other lesions (3.2% vs 0.9%, p = 0.0513). Comparing the
characteristics of patients showing incidental leiomyoma and pre-operatively
diagnosed submucosal tumor, their differences in age, gender, tumor location or
number were not significant. However, the former usually exhibited tiny lesions
without an overlying necrotic ulcer. Recent endoscopic follow-up did not find any
evidence of recurrence. CONCLUSIONS: Incidental leiomyoma is not rare in resected
specimens. Most lesions are tiny without overlying ulcer and gross recurrence
looks impossible. Pre-operative diagnosis of this lesion remains difficult since
a warning sign of leiomyoma never exists.
PMID- 9638453
TI - Effect of histamine on thyrotropin-releasing hormone and somatostatin secretion
in rat stomach.
AB - BACKGROUND/AIMS: Histamine plays an important role in gastric function, and the
histaminergic system is involved in the regulation of neuropeptides and gastric
acid secretion. METHODOLOGY: We investigated the effect of histamine and
histamine receptor antagonist (HRA) on the intraluminal secretion of thyrotropin
releasing hormone (TRH) and somatostatin (SOM) using a rat luminal perfusion
model. RESULTS: Intravenous administration of histamine caused an increase in TRH
secretion and a decrease in SOM secretion preceding a decrease in pH in the
perfusate. When the total contents of TRH and SOM in the perfusate were
calculated after administration of histamine, the effect of histamine was found
to be dose-dependent in both neuropeptide secretions. Under basal conditions,
neither H1RA, H2RA, nor H3RA caused changes in TRH secretion into the perfusate.
In contrast, H2RA and H3RA yielded an increase in basal SOM secretion. When
administered before the injection of histamine, H2RA caused a complete inhibition
of histamine-induced changes in TRH and SOM secretion. Preadministration of H3RA
also induced a weak but significant inhibition of the changes in neuropeptide
secretion. CONCLUSION: It was concluded that paracrine pathways do exist among
histamine, TRH, and SOM in the regulation of gastric acid secretion.
PMID- 9638454
TI - Gastroenterological surgery for patients with chronic respiratory insufficiency.
AB - BACKGROUND/AIMS: The aim of this study was to clarify the surgical indications
for patients with chronic respiratory insufficiency. METHODOLOGY: Fourteen
patients with chronic respiratory insufficiency who underwent abdominal surgical
procedures, were retrospectively studied. The surgical indications were carefully
determined based primarily on the performance status (PS) of each patient and
cardiopulmonary function tests. A PS of equal to or less than 3, which meant the
patient's status required bed rest > 50% of the time, and the need for assistance
in performing normal activities were all factors considered for surgical
indications. RESULTS: During the period studied, two patients were excluded from
the surgical indications due to the fact that one was at a terminal stage of
pulmonary disease and was completely bedridden (PS = 4), while the other
demonstrated active pneumonia with a considerable amount of purulent sputa.
Regarding the pulmonary function tests for patients who underwent surgery, the
lowest limits of those examinations were as follows: 810 ml of vital capacity
(VC), 23.8% of predicted VC, 610 ml of forced expiratory volume in one second
(FEV1.0), 38.6% of predicted FEV1.0, 50.5 mmHg of PaO2 while inhaling 4 liters of
oxygen and 73.8 mmHg of PaCO2. No surgery related mortality or hospital death
within 30 days after operation was observed. Only two patients had
cardiopulmonary complications (consisting of pulmonary edema with atrial
fibrillation in one patient, and acute myocardial infarction in another patient).
However, neither pneumonia, prolonged ventilatory support for more than 2 days,
nor the need for a tracheostomy after surgery was observed. CONCLUSIONS:
Gastroenterological surgery is thus considered to be indicated even for patients
with chronic respiratory insufficiency, as long as the PS can be maintained (PS
of equal to or less than 3) and no active pneumonia with a considerable amount of
purulent sputa is present.
PMID- 9638455
TI - Histologic types and surveillance of gastric polyps: a seven year clinico
pathological study.
AB - BACKGROUND/AIMS: This is a seven-year prospective study based on all gastroscopic
examinations of our patient population in order to study gastric polyps.
METHODOLOGY: One hundred and twenty-one polyps, removed from 96 patients were
analysed. All polyps, after endoscopic polypectomy, were classified according to
their histotype. The follow-up was carried out in 49 patients for a mean time of
40 months. RESULTS: Polypoid lesions were more frequent in females (57.3%) and
they were preferentially located in antrum (60.3%). Hyperplastic and inflammatory
polyps were 55.4% and 28.9%, respectively, while adenomatous lesions were 9.9%.
Four fundic gland polyps, 1 carcinoid, 1 type I early gastric cancer and 1
pancreatic heterotopia were also found. During the follow-up no malignant lesion
was encountered. On the other hand 25 benign polyps were found in 19 patients.
CONCLUSIONS: Our experience confirms that there is a close relationship between
the size of the polyps and the neoplastic change. In fact, in our series all
polyps were smaller than 2 cm and only one malignancy was found (an early gastric
cancer). None of adenomatous polyps was associated with gastric adenocarcinoma.
Our data also indicates that when a polypectomy is carried out for small polyps
(smaller than 2 cm.) a strict follow-up is necessary for the neoplastic polyps
only.
PMID- 9638456
TI - Poor prognosis in early gastric cancer complicated by five or more positive
nodes.
AB - BACKGROUND/AIMS: Despite the increased frequency of early gastric cancer, little
is known about the clinicopathological features of early gastric cancers
complicated by lymph node metastasis. This study was designed to determine
whether the number of involved lymph nodes is associated with prognosis in
patients with early gastric cancer. METHODOLOGY: Fifty one patients with node
positive early gastric cancer were reviewed retrospectively from hospital
records. The patients were divided into two groups according to the number of
positive nodes: a) 40 patients with 1-4 positive nodes, b) 11 patients with 5 or
more positive nodes. RESULTS: The patients with 5 or more positive nodes showed
poorer prognosis than patients with less than 5 positive nodes. CONCLUSIONS:
Early gastric cancer patients with 5 or more positive nodes show a poorer
prognosis than early gastric cancer patients with less than 5 positive nodes.
Since surgery alone cannot completely cure patients with early gastric cancer
complicated by 5 or more positive nodes, intensive postoperative chemo
immunotherapy should be administered to these patients.
PMID- 9638457
TI - The course of Helicobacter pylori infection after partial gastrectomy for peptic
ulcer disease.
AB - BACKGROUND/AIMS: While the number of patients operated on for peptic ulcer
disease is decreasing, many underwent surgery before the Helicobacter pylori era.
Some of them later develop ulcer relapses. The aim of this study was to evaluate
the course of H. pylori infection in the gastric remnant after surgery for peptic
ulcer disease. METHODOLOGY: This study included 90 consecutive partial
gastrectomy patients, obtained from gastroscopy registers of the Department of
Surgery, Helsinki University Central Hospital, between 1985 and 1988, in whom
both pre- and postoperative samples were available. All of the patients had
undergone partial gastrectomy at some time between 1925 and 1988. The median
interval between operation and reference gastroscopy was 5 years. RESULTS: Twenty
three patients had a recurrent ulcer, and an additional six patients had a
history of an earlier ulcer recurrence. Preoperative H. Pylori infection (68%)
did not correlate significantly with the ulcer recurrence rate. The recurrence
rate was higher in patients with Billroth I (BI) (27%) and Billroth II (BII)
(33%) reconstructions than in those with a Roux-en-Y type reconstruction (9%, BII
vs Roux-en-Y, p = 0.02, BI vs Roux-en-Y, p = 0.12). At the time of reference
gastroscopy, the proportion of H. pylori positive patients was 38%. The presence
of H. pylori at the time of reference gastroscopy did not correlate with ulcer
recurrence. A recurrent. ulcer was more often found in patients with
histologically normal gastric mucosa in the stump than in those with H. Pylori
infection (35% and 19%, p = 0.25). CONCLUSIONS: A persistent H. pylori infection
is frequently seen in the gastric remnant after operation for peptic ulcer
disease, but the infection does not seem to cause ulcer relapses in the gastric
stump or in the anastamosis.
PMID- 9638458
TI - Results of resection of gastric cancer with distant metastases.
AB - BACKGROUND/AIMS: The present study was carried out in order to examine the
outcome of resection in cases of gastric cancer with distant metastases.
METHODOLOGY: The survival rates of two hundred and eighty-one patients who had
undergone resection for primary carcinomas of the stomach, and who had distant
metastases according to the TNM classification, were studied. RESULTS: The 5-year
survival rates for patients with metastasis to the peritoneum or group 3 nodes
were 8.9% and 15.3% respectively and were significantly higher than the survival
rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or
to more than one site among the liver, lymph nodes and peritoneum (3.5%).
Moreover, the 5-year survival rates for patients with metastasis to the
peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively,
when curative surgery was performed. CONCLUSIONS: The findings of the present
study suggests that metastases to the adjacent peritoneum or group 3 nodes have a
greater chance of being cured using radical surgery, and that gastrectomy with
extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there
is no gross evidence of metastasis to the distant peritoneum, liver or group 4
nodes.
PMID- 9638459
TI - Intraoperative enteroscopy in obscure gastrointestinal hemorrhage.
AB - Forty three patients were diagnosed to have obscure gastrointestinal hemorrhage
(OGH) between January 1987 and April 1996. Pre-operative diagnostic
investigations were useful in localizing the site of bleeding in 28 patients
(65.1%). These included small bowel enema (n = 12), erythrocyte tagged scan (n =
8), Meckel's scan (n = 2) and selective visceral angiography (n = 7). Following
complete evaluation all patients underwent exploratory laparotomy. At laparotomy
31 patients were found to have gross lesions. Intraoperative enteroscopy (IOE)
could detect lesions in 9 of the remaining 12 patients.
PMID- 9638460
TI - The duodenal diverticulum: an exceptional site of massive bleeding.
AB - Duodenal diverticula are usually asymptomatic but may induce major hemorrhage on
rare occasions. When endoscopy cannot determine the cause of bleeding,
angiography must be performed. This paper describes a patient in whom angiography
identified the diverticulum as the bleeding source, which was an exceptional
occurrence, and thereby allowed prompt, appropriate treatment.
PMID- 9638461
TI - Gastric antral vascular ectasia (the watermelon stomach): a brief case report.
AB - Herein, the endoscopic and histological features of a case of gastric antral
vascular ectasia (watermelon stomach) occurring in a 76-year-old woman are
described. The condition, first recognized by Jabbari et al in 1984, is a rare
but important cause of severe gastrointestinal blood loss and chronic iron
deficiency anemia. Differential diagnosis from portal hypertensive gastropathy,
treatment and outcome of the watermelon stomach are discussed.
PMID- 9638462
TI - Current status and future challenges of tympanoplasty.
AB - Four decades after the introduction of tympanoplasty, the goal of achieving
stable and long-term hearing improvement after tympanoplasty surgery for chronic
otitis media continues to be elusive. In this review, we focus on the current
status of our understanding of the mechanics and pathology of the middle ear
after tympanoplasty surgery. We also analyze some problems and challenges faced
by clinicians and basic scientists in the quest for improved postoperative
hearing results.
PMID- 9638463
TI - Long-term rail stance training in healthy young adult women.
AB - Daily rail stance training was performed for no longer than 3 months on 12
healthy Japanese women volunteers with eyes open and closed. Rail width
conditions were varied, during which time rail stance was repeated 30 times every
day until volunteers could stand for 60 s in at least half the trials.
Prolongation of stance time and retention of training effects were investigated.
The rate of progress depended on the difficulty of the stance and was determined
by rail width and visual conditions. However, marked differences were seen among
subjects even under the same training conditions. The faster the progress, the
better preserved was the training effect during the post-training period. There
was no obvious difference in the learning curve between narrow rails with eyes
open and wide rails with eyes closed. We concluded that the retention of the
training effect parallels the rate of progress, and this is determined by the
difficulty of action relative to the inherent ability of the subjects.
PMID- 9638464
TI - Cytochemical and patch-clamp studies of calcium influx through voltage-dependent
Ca2+ channels in vestibular supporting cells of guinea pigs.
AB - To clarify whether or not vestibular supporting cells have voltage-dependent Ca2+
channels, cytochemical and patch-clamp studies were performed using cells
isolated from the ampullae of the semicircular canal of the guinea pig. Image
analysis used fura-2 as a Ca(2+)-sensitive fluorescence dye and showed that the
intracellular Ca2+ concentration ([Ca2+]i) increased with bath application of
high (150 mM)K+, but was unaffected by 80 mM K+. The increase in [Ca2+]i induced
by high K+ was completely blocked by 1 microM nifedipine as an L-type Ca2+
channel antagonist. In the patch-clamp whole-cell recording of the isolated
supporting cells, the voltage-dependent inward current was induced by a
depolarizing pulse lasting 2 s in a high (50 mM) Ca2+ and tetraethylammonium
containing external solution replaced by choline chloride and a Cs(+)-containing
internal solution. The inward current was obtained when the membrane was
depolarized to -50 mV and maximum current was observed at -10 to +10 mV. This
inward current was completely blocked by 1 microM nifedipine. These findings
strongly suggest that voltage-dependent Ca2+ channels exist in the vestibular
supporting cells and regulate Ca2+ concentration in the vestibular endolymph.
PMID- 9638465
TI - Hearing in the MRL/lpr mouse as a possible model of immune-mediated sensorineural
hearing loss.
AB - In order to clarify the possible mechanism of hearing loss in immune-mediated
sensorineural hearing loss, basic research needed includes animal model studies.
In the present investigation, we examined hearing thresholds and cochlear
histologies of the MRL/lpr mouse which is now well-known as a model for pathology
consistent with systemic lupus erythematosis (SLE). Present findings demonstrated
that there were no statistically significant differences in auditory brainstem
response (ABR) thresholds between 4- to 6-week-old "young" and 20- to 25-week-old
"old" MRL mice. These differences were not sex-dependent. Under light microscopy,
there were no abnormal morphological findings in the cochleas of either young or
old MRL mice. With immunohistochemistry, mouse IgG was detected around the
capillary walls in the stria vascularis in both young and old MRL mice. Serum IgG
level of the MRL mice significantly decreased after predonisolone (PSL)
administration. However, expression of mouse IgG in the stria vascularis was not
observed in the MRL mice after PSL administration. From these results, we
speculate that the hearing of the MRL mouse does not always deteriorate, and the
deposition of mouse IgG on the capillary wall in the stria vascularis is not a
sufficient factor to induce hearing loss. At this point, we conclude that the MRL
mouse should not be considered a useful model for immune-mediated sensorineural
hearing loss.
PMID- 9638466
TI - In vitro measurements of aerodynamic characteristics of an improved tracheostoma
valve for laryngectomees.
AB - Tracheostoma valves are often required in the rehabilitation process of speech
after total laryngectomy. Patients are thus able to speak without using their
hands to close the tracheostoma. The improved Groningen tracheostoma valve
consists of a "cough" valve with an integrated ("speech") valve, which closes for
phonation. The cough valve opens as the result of pressure produced by the lungs
during a cough. The speech valve closes by the airflow produced by the lungs,
thus directing air from the lungs into the esophagus at a deliberately chosen
moment. An experimental setup with a computer-based acquisition program was
developed to measure the pressure at which the cough valve opened and the flow at
which the speech valve closed. In addition, the airflow resistance coefficient of
the tracheostoma valve was defined and measured with an open speech valve. Both
dry air from a cylinder and humid expired air were used. Results showed a
pressure range of 1-7 kPa to open the cough valve and a flow range of 1.2-2.7 l/s
to close the speech valve. These values were readily attained during speech,
while the flow range occurred above values reached in quiet breathing. The device
appeared to function well in physiological ranges and was optimally adjustable to
an individual setting. No significant differences were measured between air from
a cylinder and humid expired air. Findings showed that methods used to obtain
results could be employed as a reference method for comparing aerodynamic
characteristics of tracheostoma valves.
PMID- 9638467
TI - Endolaryngeal high-frequency ultrasound.
AB - High-frequency ultrasound can provide high-resolution imaging for diagnosing
diseases of the head and neck. Over the last few years, a virtual technical
evolution has led to the development of small and flexible ultrasound transducers
with even greater anatomic resolution. The aim of the present study was to
evaluate the efficacy of this new technique for imaging normal and altered
anatomical structures of the endolarynx. Specially developed high-resolution,
real-time ultrasound transducers (10 and 20 MHz) placed on the tip of endoluminal
catheters were inserted into 20 autopsied larynges and five laryngectomy
specimens. In a standardized examination process the endolarynx was analyzed in a
real-time mode. Using this technique, exact 360 degrees cross sections of the
larynx were obtained, demonstrating that it was possible to image the structures
of the endolarynx with ultrasonography. Depending on the frequency used, all
anatomical structures could be visualized up to a depth of 2 cm. In laryngeal
cancer the depth of tumor as well as its relationship to the laryngeal framework
could be clearly recognized. These findings suggest that this new endoluminal
sonographic procedure represents a potentially important diagnostic tool in the
assessment of laryngeal carcinoma.
PMID- 9638468
TI - Diffuse idiopathic skeletal hyperostosis causing obstructing laryngeal edema.
AB - Diffuse idiopathic skeletal hyperostosis (DISH), or ankylosing hyperostosis
("Forestier's disease"), is an ossifying diathesis of unknown etiology. Diagnosis
is primarily radiologic: osseous bridging of at least four contiguous vertebral
bodies, a radiolucent line between the deposited bone and the anterior vertebral
surface, large osteophytes and preservation of disk height especially in the
cervical and lumbar spine. Although DISH is found in 6-12% of autopsy cases,
clinical features are rare and consist primarily of swallowing disorders. A case
of DISH is reported in which excessively enlarged cervical osteophytes led to
edema of the laryngeal inlet and consequent severe dyspnea, necessitating
emergency tracheotomy. Surgical excision of the osteophytic masses resulted in
relief of symptoms. Symptomatology, radiographic features and individual
treatments are discussed, with the latter dependent on clinical symptoms.
PMID- 9638469
TI - Anatomic relationships between surgical landmarks in type b and type c
infratemporal fossa approaches.
AB - Anatomic relationships of the structures exposed in type B and C infratemporal
fossa approaches were studied in 20 temporal bones. The intrapetrous carotid
artery (ICA), cochlea (CH), eustachian tube (ET), foramen spinosum (FS), foramen
ovale (FO) and anterior foramen lacerum (AFL) were exposed by drilling of the
glenoid fossa and base of middle cranial fossa. The relationships of the ICA with
the cochleariform process (CP), CH, ET, FS, FO and AFL were noted along with
associated measurements. The CP was lodged at a mean distance of 9.2 mm from the
ICA genu. The ET was found to intersect the ICA. The mean distance of the ICA to
the CH was 1.6 mm. The carotid canal was dehiscent on its horizontal portion in
30% of the bones studied and on its vertical portion in 5%. The periarterial
venous plexus was found in 70% of the bones. No obvious branch was observed
emerging from the vertical portion of the ICA. The FS was found to be a canal
having a mean length of 5.8 mm.
PMID- 9638471
TI - Tortuous common carotid artery encountered during neck dissection.
AB - Anomalies of the carotid artery are rare in clinical experience. To our knowledge
a tortuous common carotid artery with an abnormal course encountered during neck
dissection has never been reported in the available world literature. During
dissection of the lower neck in a 60-year-old Korean man, a tortuous right common
carotid artery was found to cross over the lower cervical trachea anteriorly and
then was positioned in its usual site in the carotid sheath in the mid-neck.
PMID- 9638470
TI - Flow cytometric analysis of DNA content and Ki-67-positive fractions in the
diagnosis of salivary gland tumors.
AB - To explore the utility of flow cytometry (FCM) for the diagnosis of
histopathology of salivary gland tumors, fresh materials taken at surgery from 23
Warthin's tumors, 57 pleomorphic adenomas, and 14 malignant tumors were analyzed
for DNA ploidy and proliferative cell activities, including S-phase fraction
(SPF), G2- plus M-phase fraction (G2M), and Ki-67-positive fraction. To
facilitate this study, glands were taken from all major salivary sites and minor
glands in the head and neck. DNA aneuploidy was not detected in the benign
tumors. Nine of 14 malignant tumors showed DNA aneuploidy. The percentage of SPF
or G2M of the malignant tumors was significantly higher than those of the benign
tumors. The percentage of Ki-67-positive fraction of pleomorphic adenomas was
comparable to that of malignant tumors and was significantly higher than that of
Warthin's tumors. Ki-67 of 20% as a cut-off had a sensitivity of 88%, specificity
of 100%, and accuracy of 91% for differentiating pleomorphic adenomas from
Warthin's tumors. In analyzing DNA content and proliferative activities by FCM,
we could distinguish among the three major histopathologies of salivary gland
tumors. Warthin's tumors showed low SPF + G2M with low Ki-67, pleomorphic
adenomas had low SPF + G2M with high Ki-67, and malignant tumor showed high SPF +
G2M with high Ki-67. The high percentage of the Ki-67-positive fraction seen in
pleomorphic adenomas may reflect their potential biological aggressiveness
manifested as tumor recurrence or malignant transformation.
PMID- 9638472
TI - A murine model system for detection of neoplasia of the head and neck using
transfectomas and carcinoembryonic antigen transgenic mice.
PMID- 9638473
TI - Heterogeneity in the clonal T cell response. Implications for models of T cell
activation and cytokine phenotype development.
AB - The T cell can be defined in the context of two properties--the recognition
specificity of the T cell receptor (TCR) heterodimer and the functional response
of the T cell after TCR stimulation. Once a particular TCR heterodimer is
expressed and successfully selected during thymic development, the antigen
specificity is fixed for all the clonal progeny of that cell. In contrast, the
potential functional responses that may be generated in response to specific
antigen in the postthymic environment are quite extensive. These range from
programmed cell death to initiation of alternate programs of phenotype
development that generate effector populations with distinct cytokine expression
patterns and regulatory properties. Recent advances in analytical methods that
have permitted multiparametric characterizations of the T cell response at the
single cell, rather than population level, have necessitated a modified view of T
cell activation and the clonal T cell response, and have generated new insights
into the regulation of immunity. In this brief review, we highlight studies that
have characterized heterogeneity of the CD4+ T cell clonal response based on
single-cell analyses, and discuss implications for models of T cell activation
and cytokine phenotype development.
PMID- 9638474
TI - Regulation of adaptive immunity by natural killer cells.
AB - Natural killer (NK) cells are well recognized as cytolytic effector cells of the
innate immune system. In the past several years, the structure and function of NK
cell receptors for the major histocompatibility complex (MHC) class I molecules
and other ligands have been the subject of extensive studies. These studies.
These studies have focused largely on the mechanisms of target cell recognition
for lysis. Another aspect of NK cell function that seems to be underappreciated
is their role in immune regulation. Since NK cells produce a number of
immunologically relevant cytokines, it has been suggested that these cells may
modulate the development of the adaptive immune response. But, is it the only
mechanism by which NK cells interact with cells involved in the induction of
antigen-specific responses? This article reviews some older and more recent
studies and attempts to place NK cells in the context of potent immune regulators
of T cell responses.
PMID- 9638475
TI - The intercellular adhesion molecule (ICAM) family of proteins. New members and
novel functions.
AB - Macromolecular adhesive associations between cells are important for transmitting
spatial and temporal information that is critical for immune system function. One
such group of proteins, the intercellular adhesion molecules (ICAMs), has grown
as newly identified members are revealed. In addition, the functions of the
ICAMs, in general, have begun to be better understood, including intracellular
signaling events. This information has led to the design of novel therapeutic
agents that may prove effective in a variety of disease states.
PMID- 9638478
TI - Cytological changes and conjunctival hyperemia in relation to sensory eye
irritation.
AB - In general, irritation is a physiological response to a chemical or physical
stimulus involving objective changes (e.g., local redness and edema) and
subjective sensations (e.g., pruritus and pain). The perception of an irritating
stimulus in the eyes and the upper airways is called sensory irritation. Sensory
irritation is a prevalent symptom in relation to complaints about indoor air
quality. The intensity of perceived sensory irritation in humans has mainly been
evaluated using psychophysical methods. However, perceived sensory irritation is
dependent on the subject expressing the symptoms; that is, it is a subjective
measure. This is a problem in assessment of irritation effects from air pollution
or other factors, since the expression of the irritation symptoms may be biased
by, for example, interaction with other people and odors. The subjectivity of the
measures is an important complication in several studies dealing with problems
regarding indoor air quality. The bias problems make it important to complement
the psychophysical measurements of sensory irritation with objective assessments
of irritation. In addition, only little is known about the association between
sensory irritation and possible physiological/ pathological changes in the
mucosal membranes in relation to studies of indoor air. Two studies (study 1 and
study 2) were conducted to investigate changes in conjunctival hyperemia and
conjunctival fluid cytology for subjects exposed to volatile organic compounds
(VOCs) in their eyes only. Eight subjects participated in study 1. Each subject
was exposed to three different mixtures of VOCs. A total of 16 subjects
participated in study 2. Half of the subjects were exposed to 1-octene and the
other half, to n-butanol. In both studies, photographs of bulbar conjunctiva were
taken and conjunctival fluid was sampled before and after exposure. Moreover, the
perceived irritation intensities were registered continuously during exposure.
Overall, perceived irritation intensity and conjunctival hyperemia increased with
increasing exposure concentrations, whereas cytological changes in the
conjunctival fluid samples did not seen to be related to exposure concentration,
perceived irritation, or changes in conjunctival hyperemia.
PMID- 9638476
TI - The role of germinal centers for antiviral B cell responses.
AB - Germinal centers (GCs) are crucially involved in T cell-dependent B cell
responses. B cells rapidly proliferate within GCs and their Ig variable region
genes undergo hypermutation. Cognate T helper cells and antigen presented in
native form on follicular dendritic cells (FDCs) select B cells expressing high
affinity Igs, leading to affinity maturation and the generation of memory B
cells. In addition to these well-established functions of GCs, this article
presents evidence that they also play a crucial role for the maintenance of
specific memory Ig titers and for the prevention of viral antibody escape
mutants.
PMID- 9638479
TI - Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5
hexanedione concentration in the sciatic nerve, serum, and urine of rats.
AB - OBJECTIVE: To clarify changes in the serum, nerve, and urinary levels of 2,5
hexanedione (2,5-HD) in rats on coadministration with methyl ethyl ketone (MEK),
acetone (AC), and toluene (TO). METHOD: 2,5-HD alone or combined with MEK, AC,
and TO was injected subcutaneously into a total of 306 male Wistar rats. The rats
were divided as follows into 7 groups: (1) 2.6 mmol/kg 2,5-HD alone (HD) and (2)
2.6 mmol/ kg 2,5-HD combined with 2.6 mmol/kg MEK (HD + MEK), (3) with 2.6
mmol/kg AC (HD + AC), (4) with 2.6 mmol/kg TO (HD + TO), (5) with 13.0 mmol/kg
MEK (HD + 5MEK), (6) with 13.0 mmol/kg AC (HD + 5AC), and (7) with 13.0 mmol/kg
TO (HD + 5TO). 2,5-HD concentrations in the serum, sciatic nerve, and urine of
rats were determined within 16 h of the injections and pharmacokinetic parameters
were estimated. RESULTS: It was observed that (1) the 2,5-HD concentration and
AUC value (area under concentration versus time curve) determined in the serum
and nerve increased significantly in the cotreated groups as compared with the HD
group; (2) the effect MEK had in elevating the 2,5-HD concentration and AUC in
the serum and nerve was stronger than that of AC, and the effect AC had was
stronger than that of TO; (3) a. dose increase from 2.6 to 13.0 mmol/kg for MEK
and AC induced further increases in the 2,5-HD concentration and AUC determined
in the serum and nerve; (4) elimination constants recorded for 2,5-HD (Ke) from
the serum and nerve decreased in all the cotreated groups, and the degree of the
decrease correlated inversely with the elevation in 2,5-HD concentration and AUC
in the serum and nerve; and (5) urinary 2,5-HD concentrations measured in the
13.0-mmol/kg cotreated groups increased in parallel with the elevation in serum
2,5-HD concentrations. CONCLUSION: Coadministration of 2,5-HD with MEK, AC, or TO
can increase the concentration and AUC of 2,5-HD in serum and the sciatic nerve,
and these increases can be further enhanced by an increase in the concomitant
doses of MEK and AC.
PMID- 9638480
TI - Update of cancer incidence among workers at a copper/nickel smelter and nickel
refinery.
AB - OBJECTIVES: To assess cancer risk among nickel-exposed workers. METHODS: We
updated cancer incidence among 1388 workers employed for at least 3 months at a
copper/nickel smelter and nickel refinery in Harjavalta, Finland. There were 1155
workers exposed to nickel during the period 1960-1985 in the smelter (566
workers), repair shop (239 workers), or refinery (418 workers). Cancer incidence
was followed through the files of the Finnish Cancer Registry up to 31 December
1995. For overall cancer and for a priori selected specific cancer types the
ratio of observed to expected numbers of cases was computed as a standardized
incidence ratio (SIR), controlled for age, gender, and calendar period and using
the region-specific rates as a reference. RESULTS: The overall cancer incidence
among both nickel-exposed and unexposed subcohorts was at the expected level. A
small increase in lung cancer incidence, which reached statistical significance
among workers with a latency exceeding 20 years, was observed among the smelter
workers exposed to insoluble nickel compounds. Among workers in the refinery, who
were exposed primarily to nickel sulfate at levels below 0.5 mg/m3 as well as to
low concentrations of other nickel compounds, there was an increased risk for
nasal cancer (SIR 41.1, 95% CI 4.97-148), positively associated with latency and
duration of employment, and an excess risk for stomach (SIR 4.98, 95% CI 1.62
11.6) and lung (SIR 2.61, 95% CI 0.96-5.67) cancers. CONCLUSIONS: Since elevated
nasal and lung cancer risks were confined to the refinery, where the primary
exposure was to nickel sulfate, it is likely that nickel sulfate is mainly
responsible for the elevated respiratory cancer risk. We cannot rule out whether
the excess stomach cancer risk is a chance finding, or related to the working
environment.
PMID- 9638477
TI - Thymopentin and splenopentin as immunomodulators. Current status.
AB - Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Arg-Lys-Asp-Val
Tyr) are synthetic immunomodulating peptides corresponding to the region 32-34 of
a splenic product called splenin (SP) and the thymic hormone thymopoietin (TP),
respectively. TP was originally isolated as a 5-kDa (49-amino acids) protein from
bovine thymus while studying effects of the thymic extracts on neuromuscular
transmission and was subsequently observed to affect T cell differentiation and
function. TP I and II are two closely related polypeptides isolated from bovine
thymus. A radioimmunoassay for TP revealed a crossreaction with a product found
in spleen and lymph node. This product, named splenin, differs from TP only in
position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and
it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5),
reproduce the biological activities of TP and SP, respectively. It is now evident
that various forms of TPs were created by proteolytic cleavage of larger proteins
during isolation. cDNA clones have been isolated for three alternatively spliced
mRNAs that encodes three distinct human T cell TPs. The immunomodulatory
properties of TP, SP, TP-5, SP-5 and some of their synthetic analogs reported in
the literature have been briefly reviewed.
PMID- 9638481
TI - Evaluation of urinary cadmium and lead as markers of background exposure of
middle-aged women in Korea.
AB - OBJECTIVE: The present study was initiated to investigate the validity of cadmium
(Cd) and lead (Pb) in urine in comparison with the metals in blood as a
biological marker of nonoccupational exposure of general populations to these
metals as environmental pollutants. DESIGN: Peripheral blood samples, morning
spot-urine samples, and 24-h total food duplicate samples were collected from 107
nonsmoking women (aged 30-59 years) in four urban and rural survey sites in
Korea. METHODS: Portions of the samples were digested by heating in the presence
of mineral acids, and the digests were analyzed for Cd and Pb by graphite furnace
atomic absorption spectrophotometry. The metal concentrations in urine were
adjusted for creatinine concentration and a specific gravity of 1.016. The
analyte levels were evaluated on an individual basis (n = 107) and also on a
group basis, i.e., in terms of geometric means for the survey sites (n = 4).
RESULTS: Cd in urine correlated with Cd in blood on an individual as well as
survey-site basis and tended to correlate with Cd in food duplicates on a group
basis. The correlation of Pb in urine with Pb in blood was weaker than that of Cd
in urine with Cd in blood when evaluated on an individual and survey-site basis.
Pb in urine correlated with Pb in food duplicates either weakly or even
negatively when examined on a survey-site basis. CONCLUSIONS: Cd in urine proved
to be valid as a biological marker of environmental exposure of general
populations, whereas less support was obtained for Pb in urine as an exposure
marker.
PMID- 9638482
TI - Erythrocyte antioxidant enzyme activities in coal miners from three French
regions.
AB - This study investigated whether differences in the prevalence and severity of
coal workers' pneumoconiosis (CWP) between three coal mines could be related to
differences in oxidative stress exposure as evaluated in vivo through red-blood
cell antioxidant enzyme activities. Blood samples were obtained from 229 miners
selected according to their occupation and their pneumoconiotic status. The
following biomarkers were evaluated: erythrocyte catalase, Cu2+/Zn2+ superoxide
dismutase (Cu2+/Zn2+ SOD), and glutathione peroxidase activities. Antioxidant
enzyme activities did not differ significantly between the group of surface
workers in Lorraine and the group of underground miners without CWP in Lorraine
and in the other coal mines. Erythrocyte Cu2+/Zn2+ SOD activity was slightly
decreased in the group of active underground miners with simple pneumoconiosis as
compared with the group of miners without CWP in Nord/Pas-de-Calais. No effect
was seen between retired miners at different stages of CWP. Our findings indicate
that differences in the prevalence and severity of CWP do not seem to be related
to various oxidative activities of coal dust particles, at least as reflected by
measurements of antioxidant enzyme activities in circulating erythrocytes in this
study.
PMID- 9638483
TI - Angular and fibrous particles in lung in relation to silica-induced diseases.
AB - INTRODUCTION: The lung concentration of angular and fibrous particles was
measured in cases of lung fibrosis only, in cases of lung fibrosis and lung
cancer, and in cases of lung cancer only. These patients worked in different
trades (mining, foundries, construction and were not a homogeneous group of
exposed workers. MATERIAL AND METHODS: Particles, both angular and fibrous, were
extracted from lung parenchyma by a bleach digestion method, mounted on copper
microscopic grids by a carbon replica technique, and analyzed by transmission
electron microscopy (TEM) and energy-dispersive spectroscopy (EDS). The quartz
concentration was also determined by X-ray diffraction (XRD) on a silver membrane
filter after extraction from the lung parenchyma. RESULTS: (1) Lung cancer and
lung fibrosis cases retained more metal-rich particles (P = 0.02) and more
angular particles of all sorts (P = 0.009) than did lung fibrosis cases only, and
the differences were statistically significant. (2) However, more quartz was
retained in the lungs in lung fibrosis cases than in lung fibrosis or lung cancer
cases, but the difference in the concentrations was not statistically
significant. (3) More ferruginous bodies were retained in the lungs in lung
cancer and lung fibrosis cases than in cases of lung fibrosis only, and the
difference in the concentrations was statistically significant (P = 0.02).
CONCLUSION: Results obtained from lung tissue must always be interpreted
cautiously. However, these results are consistent with the hypothesis that
workers in some trades such as foundries were exposed not only to quartz but also
to asbestos, ceramic fibers, metal-rich non fibrous particles, and other likely
carcinogenic chemicals. The wide range of particle types identified in the lungs
of these workers illustrates the complexity of trying to determine disease
origins in these work environments. Epidemiology studies have to control for the
exposure to these carcinogens as well as for smoking habits.
PMID- 9638484
TI - Neurological and functional effects of short-term exposure to hand-arm vibration.
AB - OBJECTIVE: The aim of the present study was to quantify the sensory and
functional effects resulting from a short-duration (30 min) exposure to hand-arm
vibration. SUBJECTS AND METHODS: Nine subjects went through nine laboratory
experiments. For 32 min they grasped a handle vibrating at three different
amplitudes (5, 20, and 80 ms-2) and at three frequencies (31.5, 125, and 500 Hz).
Additionally, a reference experiment was conducted in which the handle did not
vibrate. Three sensory tests [vibration perception threshold (VPT), pressure
perception threshold (PPT), and distal sensory latency time (DSL)], two
functional tests [Purdue peg-board (PPB) and maximal voluntary force (MVF)], and
a questionnaire concerning the perceived paresthesia and numbness were completed
before, during, and after exposure. RESULTS: A 32-min period of exposure to
vibration leads to a temporary threshold shift (TTS) of the VPT and to the
development of paresthesia and numbness. The VPT appears to vary with the
exposure duration according to a first-order model with a time constant about
equal to 3 min. The TTS increases with the vibration acceleration amplitude and
is greater for an exposure frequency of 125 Hz than for that of 31.5 or 500 Hz.
It is also greater at the test frequency 125 Hz than at 31.5 Hz. The other tests
do not demonstrate any significant variation. In particular, the PPB test does
not demonstrate any loss of dexterity. CONCLUSION: After some 30 min of exposure
to vibration the VPTs are increased and paresthesia and numbness develop.
However, these do not appear to influence significantly the capacity or
performance at work.
PMID- 9638485
TI - Benzene exposure in car mechanics and road tanker drivers.
AB - The purpose of this study was to identify professional factors related to benzene
exposure and to deduce suitable safety measures. Atmospheric benzene, urinary
muconic acid (tt-MA) and leukocyte alkaline phosphatase activity (LAPA) were
evaluated among 66 car mechanics, 34 road tanker drivers, and 28 nonexposed
workers. Professional and medical questionnaires were filled in at the same time.
Atmospheric benzene was significantly higher among road tanker drivers than among
car mechanics. The arithmetic mean +/- SD, median, and geometric mean values
were, respectively, 0.48 +/- 1.49, 0.14, and 0.06 mg/m3 among car mechanics and
1.88 +/- 4.18, 0.68, and 0.65 mg/m3 among road tanker drivers. In the latter case
the increase was caused by transport of unleaded petrol and correlated with the
volume of the tank. Among car mechanics, tobacco smoking, windy conditions,
dismantling of petrol filters, and handling of petrol increased atmospheric
benzene levels. Urinary muconic acid was increased significantly among car
mechanics (148 +/- 137, 127, and 111 micrograms/g) and among road tanker drivers
(309 +/- 420, 137, and 151 micrograms/g) as compared with the controls (49 +/-
46, 33, and 33 micrograms/g). Among road tanker drivers, alcohol intake and
transportation of unleaded petrol increased the excretion of muconic acid, which
was also directly related to the volume of the tank. Among car mechanics,
professional factors (dismantling of petrol filters, handling of and washing of
hands with petrol) and nonprofessional factors (tobacco smoking and damaged skin
on the hands and forearms) increased muconic acid excretion. In the control
group, tobacco smoking increased its excretion. LAPA was not significantly
modified among exposed workers. There was a weak but significant linear
correlation between LAPA and muconic acid. These results suggest that to reduce
exposure to benzene in unleaded petrol, individual and collective safety measures
should be imposed in both occupations.
PMID- 9638486
TI - Determination of urinary 2,5-hexanedione in the general Italian population.
AB - OBJECTIVE: Determination of the urinary levels of 2.5-hexanedione (2,5-HD) was
performed in subjects belonging to the Italian general population to define the
reference value for this metabolite. MATERIALS AND METHODS: Urine samples were
collected from 123 healthy Italian subjects who had not been occupationally
exposed to n-hexane or methyl-n-butyl ketone (60 men and 63 women; 53 living in
urban areas and 70 living in rural areas; 36 smokers and 87 nonsmokers; 65 aged
above 35 years and 58 aged below 35 years). The determinations were performed by
a gas chromatography method using a flame ionization detector (FID). A quality
control step was realized by analysis of 78 of these samples by high-performance
liquid chromatography (HPLC) with UV detection. RESULTS AND DISCUSSION: The
distribution of 2,5-HD concentration was log-normal and the corresponding
centiles at the 95% confidence interval were as follows: the 50th centile, 0.270
mg/l for men and 0.191 mg/l for women; the 75th centile, 0.352 and 0.330 mg/l,
respectively, for men and women; and the 95th centile, 0.762 and 0.582 mg/l,
respectively, for men and women. The reference value, calculated as the upper
unilateral 95% tolerance interval at 95% of confidence, was 0.795 mg/l for men
and 0.627 for women.
PMID- 9638487
TI - Occupational protein contact dermatitis with type I allergy to different kinds of
meat and vegetables.
AB - OBJECTIVE: Even though occupational protein contact dermatitis is not an uncommon
finding in occupational dermatology, reports about multiple sensitizations are
rare. High-molecular-weight substances such as proteins can pass the epidermis
only if it is damaged and cause a sensitization. In a high percentage of case,
atopic dermatitis might be the cause of this damage but cannot be regarded as the
only cause. An interesting case is presented that was carefully worked up.
METHODS: Scratch, intracutaneous, and prick or prick-to-prick tests with native
occupational allergens were performed as single tests. The patient was patch
tested with the European Standard Series. The determination of allergen-specific
IgE was performed by ImmunoCAP. The results were subdivided into six classes. In
addition, oral provocations with relevant allergens were performed. RESULTS: The
skin tests showed positive type I allergies to beef, lamb, horse, and pork meat,
to pork and horse blood as well as to rye and wheat flour, raw potato, and pasta.
Weak positive reactions could be found for fowl, duck, goose, and turkey in
intracutaneous testing. The ImmunoCAP showed elevated specific IgE values for
pork meat, raw potato, and rye and wheat flour. The oral provocation did not show
any systemic or skin change. CONCLUSIONS: This case report demonstrates how an
initial case of contact urticaria turns into protein contact dermatitis. It shows
that the diagnosis can be made by means of scratch or prick tests with native
occupational allergens. The determination of allergen-specific IgE by ImmunoCAP
might be helpful, but a negative result does not exclude protein contact
dermatitis.
PMID- 9638490
TI - Clinical and manometric effects of combined external beam irradiation and
brachytherapy for anal cancer.
AB - This study evaluates anorectal function after combined tele- and brachytherapy
for anal cancer using manometric measurements and a standardized questionnaire.
Eight patients received 44 +/- 3 Gy external beam radiation followed by 20 +/- 4
Gy interstitial brachytherapy with iridium-192. Patients were examined 43 months
(range 25-83) after therapy. Maximum anal basal pressure, squeeze pressure, and
squeeze increment were significantly lower in patients (50, 163, 115 mmHg,
respectively) than in control subjects (75, 285, 180 mmHg, respectively).
Decreased anal elasticity was not observed. Anal prestretch "normalized" the
contractility of the internal and external sphincter. Thus damage to the anal
epithelium and hemorrhoidal cushions seems to be the most important mechanism
explaining reduced anal closing pressure values. The rectoanal inhibitory reflex
was observed in all but one patient. Rectal compliance was significantly reduced.
Whereas all patients could retain a water filled rectal balloon until the maximum
tolerable sensation level was reached, the rectal saline infusion test was
strongly abnormal. Four patients were perfectly continent. Four patients were
incontinent for gas and presented urgency in case of liquid stools with limited
soiling occurring once weekly or less; three of them also had urgency for solids.
Defecation frequency was increased but regular in most patients. Reduced anal
closure together with reduced rectal compliance are at the basis of stool
frequency, urgency and partial incontinence with occasional soiling. However,
enough reserve sphincter function was maintained to preserve a clinically
acceptable degree of anal continence in our patients.
PMID- 9638491
TI - Prevalence of fecal incontinence: what can be expected?
AB - Fecal incontinence is a serious problem especially for the elderly. The
epidemiology of incontinence is not well described in the literature although it
is often used as an endpoint for treatment evaluation in clinical trials.
Complete continence is often assumed to be the "normal" standard. The goals of
this study were to establish detailed prevalence rates for fecal incontinence in
a standard population and to identify differences due to age and sex. A
questionnaire about fecal incontinence and its consequences with predefined
answers was filled out anonymously by 500 volunteers. The study population was
selected to meet the respective age and sex distribution of the German adult
population. The data indicated that 4.8% of the persons were unable to control
solid stools, while 19.6% had problems at least with one type of incontinence
(solid, pasty, or lipid stools, winds). Problems with pasty or liquid stools are
more frequent in women. The ability to control wind is decreased in elderly
persons. The time needed to reach a toilet is shorter for women, and generally
decreases in the elderly. Men more often describe soiling the underwear. Persons
with signs of incontinence show decreased levels of social activities. A global
incontinence rate of 5% fits well with some previously published results. Soiling
of the underwear is not well suited for defining incontinence. The increased rate
in women may in part be explained by morphological differences. The reduced time
to hold stools especially in the elderly in combination with a reduced mobility
may result in a higher rate of incontinence, which is correlated with reduced
social activities.
PMID- 9638489
TI - Substance P containing nerve fibers in ulcerative colitis.
AB - The distribution of and morphological changes in substance P containing nerve
fibers were examined immunohistochemically in the colonic mucosa of ulcerative
colitis (UC) patients. Quantitative and morphological changes in substance P
fibers were analyzed by digitized morphometry. The linear density of substance P
fibers was significantly greater in the UC group (19.4 +/- 1.2 microns/1000
micron 2) than in the Crohn's disease group (10.1 +/- 1.2 microns; P < 0.01) and
the control group (8.4 +/- 0.8 microns; P < 0.01). Analysis of the UC group
showed that the degree of inflammation affected the linear density of substance
fibers, with "moderate" cases presenting the highest linear density and "severe"
cases the lowest. Substance P fibers were thickened and coarse in UC; they were
significantly wider in the UC group (2.5 +/- 0.5 microns) than in the Crohn's
disease group (1.5 +/- 0.2 microns; P < 0.01) and the control group (1.2 +/- 0.1
microns; P < 0.01). In conclusion, alterations in substance P containing nerve
fibers, as evidenced by both the linear density and morphology, may play some
role in the pathogenesis of UC.
PMID- 9638492
TI - New healing agent for colonic anastomosis.
AB - This study evaluated the healing property, on colonic anastomoses, of a new
compound termed RGTA11 (standing for "regenerating agent," a dextran derivative
with heparin-like properties). Colonic anastomoses were performed in 183 adult
rats after dipping both ends of the colon in solutions containing RGTA11. The
anastomoses were made end-to-end on a single plan, 8 sutures. Healing was
evaluated mechanically by the bursting pressure in 108 animals and histological
analysis in 75. Results indicated that after 48 h RGTA11-treated animals
presented a twofold increased resistance to anastomoses breakage (P < 0.01) over
nontreated (saline buffer) animals. After 96 h and until day 7 there was no
longer a difference between study and control animals. Although this difference
in breakage was not readily observed at histological level, results suggest that
RGTA11 could be used to aid colonic anastomosis healing. RGTA11 is of potential
clinical interest in this regard since complications that are known to occur
postoperatively result from early leakage.
PMID- 9638495
TI - The appropriate use of colonoscopy in the curative management of colorectal
cancer.
AB - A total of 175 patients who underwent a curative resection for a colonic (n =
130) or a rectal cancer (n = 45) between 1986 and 1992 were entered into a
routine colonoscopy program. Colonoscopies were performed 1 year after the
operation, and then at 2-year intervals. The findings at colonoscopy, as well as
those of preoperative colonoscopy (when performed), were recorded. Eleven
anastomotic recurrences were diagnosed at an asymptomatic stage, at a mean follow
up of 14 months. All of them were identified in patients with a stage B or C
primary rectosigmoid cancer. Eight patients underwent another potentially
curative re-operation. Only perioperative colonoscopy (preoperative colonoscopy;
first postoperative colonoscopy in patients for whom the preoperative procedure
was incomplete or not performed) allowed diagnosis of second cancers (n = 7) and
adenomatous polyps greater than 10 mm (n = 17). Further colonoscopies detected
only polyps less than 10 mm. Positive examination rates for successive follow-up
colonoscopies were 15, 20 and 23%, respectively; they were significantly higher
in patients who had previously had adenomatous polyps than in patients who had
not: 30% versus 6% (P < 0.025), 46% vs 5% (P < 0.005) and 38% vs 11% (P < 0.025),
respectively. From these data, the following recommendations are made: (1) All
colorectal cancer patients should have a total colonoscopy either before
(whenever possible) or soon after operation; (2) Based on results of the
perioperative colonoscopy, patients: should undergo their first follow-up
colonoscopy only 3 yearly (presence of synchronous adenomatous polyps) or 5
yearly (absence of synchronous adenomatous polyps) after resection; (3) In
patients with stage B or C primary rectosigmoid cancer, a surveillance of the
suture line by rigid proctosigmoidoscopy should be added during the first 2
postoperative years: 6, 15 and 24 months after the operation.
PMID- 9638494
TI - Outcome of patients with an implanted artificial anal sphincter for severe faecal
incontinence. A single institution report.
AB - Implantation of an artificial sphincter is an alternative treatment for patients
with severe faecal incontinence. This prospective study from one institution has
evaluated the results from 13. Preoperative and postoperative incontinence
scores, anal manometry, and quality of life were evaluated in 13 patients who had
undergone implantation of an artificial sphincter over a 7-year period. Two
patients were definitive failures. One developed acute total colitis after 5
years of satisfactory function, and a second had discomfort and demanded removal
of an otherwise functioning device. After a median follow-up of 30 (range 5-76)
months, 11 patients had an activated and functional device. These included 6 with
a urinary AMS 800 and 5 with the newly designed anal ABS. The mean incontinence
score decreased from 17 to 4, and quality of life improved markedly. Two of the
11 patients had undergone successful reimplantation, one following rupture of the
cuff and the second following ulceration of the control pump through the labia.
In no case was infection or erosion of the anal canal a cause of failure. While
the cause of incontinence and age did not affect outcome, psychological reaction
had a significant impact. The artificial anal sphincter may have a role to play
in severe faecal incontinence.
PMID- 9638493
TI - Transrectal ultrasonography: relationship with anorectal manometry,
electromyography and sensitivity tests in irritable bowel syndrome.
AB - Irritable bowel syndrome is the most frequently diagnosed disorder in
gastroenterology. It has been demonstrated with specialized motility studies that
these patients compared to healthy subjects show changes in rectoanal electrical
and mechanical activity and in rectoanal sensitivity. However, until now no
report has been published on morphological alterations in the rectum or the
internal anal sphincter. Twenty-five consecutive patients with irritable bowel
syndrome (mean age 32, range 17-47 years; 24 females) were evaluated
prospectively by transrectal ultrasonography, rectal sensitivity studies, and
recordings of both electrical and mechanical activity of the distal rectum and
internal anal sphincter during a 2-h inter-digestive period. Ten healthy
volunteers (mean age 34.5, range 19-50 years) served as a control group. Paired
and non-paired Student's two-tailed t test and linear regression analysis were
used. It was shown that muscle thickness of the rectum during rest (4.7 +/- 0.1
mm) was correlated neither with its rectal spike amplitude (0.73 +/- 0.1 mV) nor
with rectal spike frequency (17.06 +/- 3.6 spike/2 h). In addition, the diameter
of the internal anal sphincter (1.2 +/- 0.1 mm) was correlated neither with its
resting pressure, nor with frequency (17.1 +/- 3.2/2 h), duration (14.9 +/- 1.5
s), or amplitude (14.1 +/- 1.9 mmHg), of inhibition of the spontaneous rectoanal
inhibitory reflex. No correlation was found between ultrasonographic parameters
and rectal distension variables (r = 0.03). This study demonstrates for the first
time morphological anorectal changes in patients with irritable bowel syndrome
compared to healthy subjects, in addition to showing that morphological changes
are independent of physiological ones. Therefore both transrectal ultrasonography
to determine anorectal morphology and electromanometry to assess anorectal
function are important measures in the evaluation of patients with irritable
bowel syndrome.
PMID- 9638488
TI - Fistulas complicating diverticulitis.
AB - This study was undertaken to assess the appropriate management of patients with
diverticulitis complicated by fistula formation. A retrospective chart review was
conducted on patients with symptoms of a fistula who presented between 1975 to
1995. There were 42 patients (32 women, 76%; 10 men, 24%) who ranged in age from
46 to 89 years (mean 69.8 +/- 9.8). Six patients had multiple fistulas. The types
of fistulas included colovesical (48%), colovaginal (44%), colocutaneous (4%),
colotubal (2%), and coloenteric (2%). Operative procedures consisted of resection
and primary anastomosis in 38 patients and a Hartmann's operation in one. Three
patients were managed conservatively with antibiotics (two due to poor
performance status, the third due to resolution of symptoms). There were no
operative deaths. The postoperative course was uncomplicated in 69%, while 12
patients (31%) experienced 19 complications (40%). These consisted of urinary
tract infection (9.5%), atelectasis (7.1%), prolonged ileus (4.8%), arrhythmias
(4.8%) and renal failure, myocardial infarction, pseudomembranous colitis,
peroneal nerve palsy, unexplained fever, pulmonary edema (2.4% each). There were
no anastomotic leaks and no deaths. Hospital stay ranged from 6 to 31 days (mean
12.3 +/- 7.6). Fistulas due to diverticulitis were safely managed by resection
and primary anastomosis without mortality and with acceptable morbidity in this
series. Patients deemed to be poor operative risks can be managed with a course
of nonoperative treatment.
PMID- 9638496
TI - The novel combination of fat clearance and immunohistochemistry improves
prediction of the outcome of patients with colorectal carcinomas: a preliminary
study.
AB - To evaluate the significance of micrometastases in relation to survival rate,
specimens from 48 colorectal carcinoma patients were analysed after fat
clearance. The number and size of the lymph nodes harbouring metastases and the
significance of micrometastases for patients' survival were assessed. We found
that although the majority of metastatic lymph nodes (71.8%) were 5 mm or less in
diameter, their size had no effect on survival. Immunohistochemical staining of
lymph nodes revealed that 15 of 25 patients with Dukes' stage B diagnosed by
routine staining had micrometastases, 86% of these lymph nodes being less than 5
mm in diameter. The survival rate of this subgroup was found to be considerably
poorer than that of Dukes' stage B patients with no micrometastases. None of the
three patients with Dukes' stage A carcinoma had micrometastases. Since most of
the metastases and micrometastases occur in lymph nodes of 5 mm and less and can
be easily missed by routine examination, we suggest that fat clearance and
routine immunohistochemical analysis of Dukes' stage B improve the prediction of
outcome of colorectal cancer patients.
PMID- 9638497
TI - Patterns of distribution of endoscopic and histological changes in the ileal
reservoir after restorative proctocolectomy for ulcerative colitis. A long-term
follow-up study.
AB - OBJECTIVE: This study was undertaken to assess the long-term macroscopic
appearance of the ileal reservoir after restorative proctocolectomy for
ulcerative colitis, to determine whether there is any correlation between
macroscopic and histological changes and whether the distribution of these is
homogeneous, focal or patchy. BACKGROUND: No study has examined the macroscopic
appearance of the ileal reservoir over a long period and it is still unknown to
what degree histological changes are diffuse or patchy. Moreover, the
relationship between macroscopic and histological changes is poorly understood.
METHOD: Fifty-nine patients were examined by one clinician (PSC) 5.3-14.5 years
(median 8.2 years) postoperatively. A rigid sigmoidoscopy of the reservoir was
performed. Four zones in the posterior midline at 5-cm intervals from the
ileoanal anastomosis were inspected. At each level a macroscopic score of
severity of inflammation was given and a biopsy taken. The degree of acute and
chronic inflammation was assessed using a histopathological scoring system.
RESULTS: All reservoirs showed macroscopic abnormalities, which were more marked
distally in 14 (24%). There was no case in which severity of inflammation was
greater in proximal than in distal zones. Endoscopy overall correlated with both
acute and chronic histological changes. On histological examination the patients
could be divided into three groups as follows: (1) all four biopsies were normal
(group 1, n = 8, 14%), (2) the score of acute and chronic inflammation decreased
from distal to proximal zones (group 2, n = 25, 42%) and (3) all four biopsies
were abnormal with the same score (group 3, n = 26, 44%). The latter group
significantly correlated with a present or past history of pouchitis. CONCLUSION:
The study has shown that when there is a gradation of inflammation within the
ileal reservoir this is more severe in distal than in proximal zones.
PMID- 9638498
TI - Papillomavirus and anal carcinoma.
AB - Human papilloma virus (HPV; 16 and 18) is known to play an important etiologic
role in cervical dysplasia, but its relationship with anal carcinoma is still
unclear. Surgical samples from 80 female patients treated for anal epidermoid
carcinoma in the Polyclinic of Surgery in Geneva between 1976 and 1989 were
retrospectively studied. Of these, HPV detection was performed in 41 whose DNA
was preserved well enough to allow such an analysis. Seventeen (42%) samples
contained HPV, with a high percentage of high risk HPV (15/41, 36%). Thirty-eight
of the 80 patients had a cervical smear, of which 18% revealed cervical
carcinoma. When compared with epidemiological data, the results of this study
suggest that genital HPV infection predisposes not only to cervical cancer, but
also to anal carcinoma, possibly by means of contiguous contamination.
PMID- 9638506
TI - Telephone support for nurses in HIV/AIDS care.
PMID- 9638500
TI - Time course of apoptosis in collagen-induced arthritis.
AB - Recently, apoptotic cells were discovered in the synovial cells of rheumatoid
arthritis patients. Their role, however, is unknown. We thus examined the time
course of apoptosis in the synovium using an animal model of rheumatoid
arthritis, in which arthritis was induced by intracutaneous injection of
collagen. No apoptotic cells were detected before the onset of synovitis, but
they increased in parallel with the progress of arthritis in its initial period,
and decreased in the later chronic stages. Apoptotic cells appear to maintain the
homeostasis of a joint when synovial proliferation occurs.
PMID- 9638505
TI - Patients with HIV are safe to treat, says ANA.
PMID- 9638507
TI - HIV-positive nurse wins precedent-setting case in Norway.
PMID- 9638503
TI - Successful treatment of severe atopic dermatitis-complicated cataract and male
infertility with a natural product antioxidant.
AB - There has been a recent dramatic change in the features of atopic dermatitis and
male infertility, including a marked increased prevalence of severe and treatment
resistant atopic dermatitis; an increase in severe atopic dermatitis complicated
by cataracts, especially in urban and industrial areas; and an increase in the
number of infertile men with poor sperm motility. Previously we have attributed
these changes to the increased free radicals produced by environmental toxicity.
We have reported the increase in lipid peroxide levels and decrease in superoxide
dismutase inducibility in severe atopic dermatitis patients, and shown that lipid
peroxides attach to the stratum corneum, promoting loss of skin moisturization
and resulting in the worsening of atopic dermatitis. Cataracts which occur with
severe atopic dermatitis are also formed by the diffusing of lipid peroxides
through the posterior lens. Regarding aspermia, the standard levels of sperm
motility according to the World Health Organization Guidelines have been reduced
to 50% from 60%, but nonetheless the prevalence of infertile men is increasing.
It has been reported that antioxidants such as ascorbate, catalase and
glutathione-Px can reverse the decrease in sperm motility in the seminal plasma
of infertile men. We have developed an oral antioxidant, named AOA, which is
produced from natural plants and seeds (e.g., soybean, sesame, wheat germ),
treated by heating with far infrared rays (4-14 microns wavelength), brewed with
Aspergillus oryzae, and lipophilized with similarly heated sesame oil. These
procedures liberate low-molecular-weight antioxidants that exist naturally in an
inactive form of repeating subunits of polymers, to produce free, activated forms
of antioxidants. This natural medicinal product, AOA, has been applied to the
treatment of both cataract complicated with atopic dermatitis and male
infertility. Approximately half the patients tested have shown marked
improvement.
PMID- 9638508
TI - ICN promotes partnerships.
AB - Partnership is today's keyword. As it has become evident that no one institution,
group or individual can eliminate poverty, improve health status or solve any
other societal problem alone, WHO, the World Bank and other UN agencies and
nongovernmental organizations are on the search for partnerships, starting from
the international down to the local level and involving all sectors, including
private and public companies. An ICN core value, partnership is being promoted on
International Nurses' Day, May 12, and throughout the year. In this issue,
partnerships are called for in defending human rights (page 76), in curtailing
the spread of HIV/AIDS (page 85) and in a community's health development (page
81). Below, a review of how nurses can work hand in hand with their communities
and others to improve health.
PMID- 9638501
TI - Effects of a neutral endopeptidase inhibitor, BP102, on the development of
deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway
Katholiek rats.
AB - The nature of all of the peptides critical to the mechanism(s) of the
antihypertensive action of neutral endopeptidase (NEP) inhibitors is still
unclear, but bradykinin is thought to be one such peptide. This study was
designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone
acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka)
rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased
urine volume and urinary sodium excretion in a dose-dependent manner in
anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN
Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development
of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka
rats was also significantly reduced, by an 8-day administration of BP102. When
BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated
BN-Ka rats was markedly lowered, and their heart weights were reduced. These
results suggest that kinins play no role in the antihypertensive effect of this
inhibitor and that other factors may be involved in this effect.
PMID- 9638502
TI - Long-term ethanol administration enhances urinary ultraweak luminescence and age
dependent modulation of redox in central and peripheral organs of the rat.
AB - Numerous experimental evidence sustains a pathogenic role for oxidative stress in
aging. Acute and chronic ethanol metabolism is also known to be associated with
oxidative perturbation of cellular oxidant/antioxidant balance. In the present
work we investigated the effects of 25 months of ethanol consumption on the
antioxidant defense system in different organs of rats, in comparison with normal
and aged animals. We show that aged rats underwent a significant perturbation of
the antioxidant defense system, as indicated by depletion of reduced glutathione
content, increases in oxidized glutathione and free radical-induced urinary
luminescence associated with a decrease of glutathione reductase and increase of
glutathione transferase activities. These modifications, observed particularly in
the liver and brain, were enhanced by long-term alcohol exposure. Our results
indicate that increased glutathione transferase activity and decreased
glutathione reductase activity, followed by thiol depletion, are important
factors sustaining a pathogenic role for oxidative stress in aging and in all
situations where age-correlated changes occur. They also reinforce the oxidative
potential of toxic compounds, such as ethanol intoxication.
PMID- 9638499
TI - Treatment of acute pain following removal of mandibular third molars. Use of the
dental pain model in pharmacological research and development of a comparable
animal model.
PMID- 9638509
TI - Human Rights and torture.
AB - 1998 marks the 50th anniversary of the historic Universal Declaration of Human
Rights, which proclaims that all peoples are born free and equal and sets out the
basic principles of equality and nondiscrimination in the enjoyment of
fundamental freedoms and human rights. Yet, despite the many covenants and
conventions stemming from this declaration and signed by nations around the
world, human rights continue to be violated by powerful groups, by individuals,
often even by family members. On 26 June, which has been declared UN
International Day in Support of Victims of Torture, attention will be focused on
torture--a grave violation of a person's human rights still practised in its many
insidious forms in many countries. INR reviews the work of the organizations
trying to help stop the perpetrators and participation of health professionals;
rehabilitate the survivors; and educate health professionals and the public.
PMID- 9638510
TI - Teaching health professionals about torture.
PMID- 9638504
TI - Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following
inguinal hernioplasty.
AB - In this study lysine clonixinate, a nonsteroidal antiinflammatory agent with
selective inhibition of cyclooxygenase-2 and 5-lipooxygenase in in vitro and in
vivo pharmacodynamic studies, was evaluated in a prospective, randomized, double
blind, double-dummy clinical study versus paracetamol/codeine, in 151 patients
with pain following inguinal hernioplasty. Patients were treated with one 125 mg
tablet of lysine clonixinate or paracetamol/codeine (500 mg + 30 mg) administered
at fixed doses every 4 h during 2 days. Controls were carried out 1, 2 and 4 h
after the first intake of day 1 and day 2. Each control included assessment of
pain at rest, when coughing, sitting and upon moderate pressure. Both treatment
groups (lysine clonixinate, 77 patients and paracetamol/codeine, 74 patients)
were comparable in terms of demographic and baseline pain intensities.
Spontaneous pain was reduced significantly in both treatment groups from the 1st
h control. The following values were recorded in the lysine clonixinate group
during day 1: baseline: 6.86 +/- 1.24; 1st h: 4.49 +/- 1.77; 2nd h: 2.96 +/-
1.74; 4th h: 2.23 +/- 1.51. The following values for the same group during day 2
were: predose: 1.70 +/- 1.64; 1st h: 1.16 +/- 1.17; 2nd h: 0.78 +/- 1.06; 4th h:
0.63 +/- 1.05. The paracetamol/codeine group revealed the following values: day
1: baseline: 6.72 +/- 1.22; 1st h: 4.57 +/- 1.72; 2nd h: 2.97 +/- 1.68; 4th h:
2.47 +/- 1.68 and day 2: predose: 2.02 +/- 1.57; 1st h: 1.32 +/- 1.23; 2nd h:
0.82 +/- 0.99; 4th h: 0.66 +/- 0.89. Reduction of pain induced by coughing,
sitting and pressure showed similar behavior patterns. No significant differences
between both treatment groups were encountered in terms of analgesic efficacy.
Incidence of adverse effects was significantly higher in the paracetamol/codeine
group (X2: p < 0.05): 11 out of 74 patients; three patients had to discontinue
treatment. In the lysine clonixinate group four out of 77 patients showed side
effects but these did not require treatment discontinuation.
PMID- 9638511
TI - Empowering communities--a strategy used in Malawi.
AB - In Malawi, community health nurses and environmental health officers are helping
communities to solve their own health problems. Below, the lessons learned in one
district.
PMID- 9638512
TI - Nurses fighting the HIV/AIDS epidemic in Africa.
AB - Nurses involved in HIV/AIDS care must contend with many practical, professional
and ideological issues. In doing so they must also be activists for social
justice and human rights in health care, especially in countries where poverty
and lack of knowledge are inextricably linked to the spread of HIV. Below, a
report on where nurses are and should be going in Africa.
PMID- 9638513
TI - Nursing and health in Russia.
AB - There are over one million nurses in Russia, and they work in a crippled
healthcare system facing a dramatic increase in infectious diseases. But nurses
are valiantly coping with the country's health crisis and becoming a recognized
profession.
PMID- 9638514
TI - Lipoproteins and cardiovascular risk-from genetics to CHD prevention.
AB - Dyslipidemia is said to be present when lipid or lipoprotein levels lie within a
range which is known from epidemiological studies to be associated with secondary
complications, in particular atherosclerosis of the coronary arteries, or when a
lipid or lipoprotein grossly deviates from the norm as in abetalipoproteinemia,
hypobetalipoproteinemia or the HDL deficiency syndromes. In most cases,
dyslipidemia is due not to a single genetic or environmental factor, but to a
combination of the effects of several genes of small effect (polygenes) and
environment. In other cases, however, dyslipidemia is caused by a mutation in a
single gene of large effect. In such cases, the extent and nature of the
phenotype depends primarily on the identity of the gene involved, but is also
modulated to an important degree by the nature of the mutation and the genetic
and environmental background against which this mutation occurs. In addition,
many cases of hyperlipidemia are secondary to other disorders such as
hypothyroidism or renal dysfunction. Such disorders may also unmask or exacerbate
a genetic lipoprotein disorder. Examples of the latter are the unmasking of type
III hyperlipidemia by diabetes mellitus or the exacerbation of familial
hypercholesterolemia by hypothyroidism.
PMID- 9638515
TI - Vascular dopamine-I receptors and atherosclerosis.
AB - Vascular smooth muscle cell (VSMC) migration and proliferation are believed to
play key roles in atherosclerosis. To elucidate the role of vascular dopamine D1
like receptors in atherosclerosis, the effects of dopamine, specific D1-like
agonists SKF 38,393, and YM 435 on platelet-derived growth factor (PDGF) BB
mediated VSMC migration, proliferation, and hypertrophy were studied. We observed
that cells stimulated by 5 ng/ml PDGF BB showed increased migration,
proliferation and hypertrophy. These effects were prevented by coincubation with
dopamine, SKF 38,393, or YM 435 at 1-10 mumol/l, and this prevention was reversed
by Sch 23,390 (1-10 mumol/l), a specific D1-like antagonist. These actions are
mimicked by 1-10 mumol/l forskolin, a direct activator of adenylate cyclase and 8
bromocyclic AMP at 0.1-1 mmol/l. The actions are blocked by a specific protein
kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline
sulfonamide (H 89), but are not blocked by its negative control, N-[2-(N-formyl-p
chlorocinnamylamino) ethyl]-5-isoquinoline sulfonamide (H 85). PDGF-BB (5 ng/ml)
mediated activation of phospholipase D (PLD), protein kinase C (PKC) and mitogen
activated protein kinase (MAPK) activity were significantly suppressed by
coincubation with dopamine. These results suggest that vascular D1-like receptor
agonists inhibit migration, proliferation and hypertrophy of VSMC, possibly
through PKA activation and suppression of activated PLD, PKC and MAPK activity.
PMID- 9638518
TI - Effects of copper-zinc type superoxide dismutase on the proliferation and
migration of cultured vascular smooth muscle cells induced by oxidized low
density lipoprotein.
AB - We have investigated the effects of copper-zinc type superoxide dismutase (Cu, Zn
SOD) on the function of oxidized low density lipoprotein, utilizing cultured
smooth muscle cells (SMC), obtained from rabbit aorta. We added native LDL
(nLDL), minimally oxidized LDL (MmLDL) and copper ion-induced oxidized LDL
(OxLDL) to the culture media. No remarkable change was found out by adding nLDL.
The numbers of SMC, including migrated SMC, were increased by the addition of
MmLDL. Cu, Zn-SOD significantly inhibited the reactions induced by MmLDL. The SMC
numbers were markedly decreased by OxLDL addition without recovery by adding Cu,
Zn-SOD. Thus, MmLDL significantly promoted the SMC proliferation and migration.
OxLDL revealed strong cytotoxicity against SMC. Cu, Zn-SOD inhibited both the
migration and the proliferation of SMC induced by MmLDL, and did not alter the
effect of OxLDL. In conclusion, Cu, Zn-SOD inhibited some functions of MmLDL, and
may play an important role in protecting against the atherosclerotic processes
evoked by MmLDL.
PMID- 9638516
TI - Molecular mechanisms of the exaggerated growth of vascular smooth muscle cells in
hypertension.
AB - The molecular mechanisms of the exaggerated growth of vascular smooth muscle
cells (VSMC) in hypertension are reviewed based on our previous experimental
data. Spontaneously hypertensive rats (SHR)-derived VSMC increasingly express
angiotensinogen, cathepsin D and angiotensin-converting enzyme (ACE) mRNAs,
compared to cells from normotensive Wistar-Kyoto (WKY) rats, indicating the
presence of an Ang II generating system in a homogeneous culture of VSMC from
SHR. The produced Ang II then induces TGF-beta. SHR-derived VSMC show the
distinct expression and abnormal regulation by Ang II of TGF-beta receptors when
compared with cells from WKY rats, which express TGF-beta type II receptor
predominantly to induce PDGF A-chain stimulation of VSMC growth. These findings
imply that the increased growth of VSMC in hypertension is a primary event
independent of high blood pressure, and is associated with endogenous Ang II
related growth factors.
PMID- 9638517
TI - Cytotoxicity of some oxysterols on human vascular smooth muscle cells was
mediated by apoptosis.
AB - A decrease in smooth muscle cells is observed in advanced atherosclerotic lesion.
To understand this mechanism, we selected oxysterols as candidates for toxic
lipid, and examined their cytotoxicity on human cultured vascular smooth muscle
cells, together with the manner of cell death. In the presence of 7
ketocholesterol or 7 beta-hydroxycholesterol (50 mumol/L), the percentage of
detached cells increased significantly with dose dependency, and an increase in
detached cell number and DNA nick detected by terminal deoxynucleotidyl
transferase-mediated dUTP-biotin nick end labeling study (TUNEL) preceded an
increase in lactate dehydrogenase released into the medium. DNA extracted from
smooth muscle cells incubated with 7-ketocholesterol or 7 beta-hydroxycholesterol
showed a laddering pattern on agarose electrophoresis. In the presence of 7
ketocholesterol or 7 beta-hydroxycholesterol, fragmented DNA quantified by the
quantitative sandwich enzyme immunoassay was significantly increased. From these
results, it is proposed that 7-ketocholesterol and 7 beta-hydroxycholesterol are
toxic to smooth muscle cells, and that this cytotoxicity is mediated by
apoptosis.
PMID- 9638519
TI - Effects of pressor substances on low density lipoprotein peroxidation by Cu++.
AB - To investigate whether pressor substances accelerate low density lipoprotein
peroxidation by Cu++, low density lipoprotein was dialysed against physiological
saline containing O-5 mumol/l CuCl2 and/or 1 mumol/l of various pressor
substances. Lipid peroxide value of low density lipoprotein changed little with
the addition of norepinephrine to the saline, but the addition of norepinephrine
to 1 mumol/l CuCl2 accelerated the peroxidation. When low density lipoprotein was
dialysed against saline with norepinephrine, epinephrine, serotonin or dopamine,
there were no significant differences in the lipid peroxide values of low density
lipoprotein. Although the addition of serotonin into the dialyzate did not
accelerate the peroxidation of low density lipoprotein due to Cu++, the addition
of norepinephrine, epinephrine and dopamine accelerated the Cu(++)-peroxidation
with a significant increase in the acceleration rate starting at the 36 hour
point. Thus, it is speculated that various stresses stimulating the sympathetic
nervous system accelerate the peroxidation of low density lipoprotein and produce
peroxidized low density lipoprotein in the blood.
PMID- 9638520
TI - Elevation of plasma lipid peroxides in non-insulin dependent diabetics with
multiple lacunar infarcts.
AB - Our purpose was to determine whether lipid peroxides are elevated in the plasma
of patients with non-insulin dependent diabetes with multiple lacunar infarcts as
detected by magnetic resonance imaging (MRI), and to confirm whether peroxide
levels correlate with glycemic controls and blood lipid levels. The level of
lipid peroxide (measured as thiobarbituric acid reactive substances (TBARS)) was
measured in 23 healthy controls and 28 diabetics showing normal MRI findings and
22 diabetics with multiple lacunar infarcts. These groups were age-matched. In
patients with multiple lacunar infarcts, systolic blood pressure, diastolic blood
pressure and TBARS levels were significantly higher than in diabetics without
such infarcts (p < 0.05). When the diabetic patients were divided into two groups
according to the presence or absence of hypertriglyceridemia or hyperglycemia, in
both groups plasma TBARS levels in patients with multiple lacunar infarcts were
significantly higher than in patients without such infarcts. Multivariate
analysis showed systolic blood pressure and plasma TBARS levels to be independent
predictors of multiple lacunar infarcts. Among diabetics, total plasma TBARS
levels were positively correlated with fasting blood glucose, HbA1c and
triglyceride levels, but not with total cholesterol levels and age. In conclusion
plasma lipid peroxides were elevated in diabetics with multiple lacunar lesions,
and are related to the metabolic imbalance of plasma glucose and lipids.
PMID- 9638523
TI - Biocompatibility of poly(etherurethane urea) containing dehydroepiandrosterone.
AB - Poly(etherurethane urea) (PEUU) elastomers, with their broad range of mechanical
properties and high biocompatibility, are used clinically for medical
applications. However, the possibility exists for the ether soft segment of PEUU
to degrade in long-term uses. To retard degradation, antioxidants that scavenge
reactive oxygen intermediates are added. In this study, we incorporated
dehydroepiandrosterone (DHEA), which functions by the alternate mechanism of
modulating or down-regulating adherent macrophage activity, to retard the
biodegradation of PEUUs. Biocompatibility of PEUU samples containing 1% DHEA, 5%
DHEA, and 5% vitamin E (alpha-tocopherol) by weight were studied in vivo and in
vitro. The biocompatibility was initially evaluated by examination of the
inflammatory cellular exudate. Compared to PEUU without additives and PEUU with
5% vitamin E, the addition of 5% DHEA to PEUU caused a decrease in the total
leukocyte exudate concentration at 4 days. The addition of 5% DHEA also caused
lower macrophage adhesion and FBGC formation compared to the other materials at 7
days. Despite these short-term effects, the biocompatibility at later time points
(14, 21, and 70 days) was similar for all materials. Transmission infrared
analysis of the materials revealed that more than 70% of the DHEA had leached out
of the samples by 3 days implantation. Furthermore, through attenuated total
reflectance Fourier transform analysis and scanning electron microscopy, it was
determined that unlike vitamin E, DHEA did not enhance long-term PEUU
biostability. The effect of DHEA on inflammatory cell activity appeared to be
dose dependent, with improved biocompatibility in vivo for higher loading levels
of DHEA, but the overall effect was limited owing to the rapid diffusion of the
water-soluble DHEA from the PEUU.
PMID- 9638525
TI - Effects of hyaluronan viscous materials on cell membrane electrical properties.
AB - Hyaluronan [hyaluronic acid (HA)] has been implicated in various cellular
processes such as proliferation, adhesion, migration, and differentiation. The
secondary and tertiary structures of HA give it very important and unique
viscoelastic properties. HA-composed materials are currently used intraocularly
during ophthalmological surgery to facilitate surgical procedures and prevent
tissue damage. To examine the effects of three viscous biomaterials composed of
hyaluronan (Healon, IAL, and Biolon) used in ophthalmological surgery, the
membrane electrical properties of the erythroleukemic K562 cell line exposed to
these materials were investigated. Membrane conductivity, membrane permittivity,
and the conductivity of the cytosol were evaluated using dielectric relaxation
measurements in the radiofrequency range and fitting the experimental results to
the general equations of the Maxwell-Wagner effect. The results demonstrate that
while membrane permittivity and the conductivity of the cytosol are not
significantly altered, the membrane conductivity of K562 cells exposed to all
three biomaterials increases substantially and in a time-dependent manner with
respect to untreated cells. These observations seem to indicate that hyaluronan
perturbs ionic transport while it does not vary the type, quantity, or
distribution of membrane components. In addition, the variations induced by these
substances on the cell membrane are not dependent upon the molecular weight or on
the biological origin of hyaluronan. These results may aid in elucidating the
mechanisms involved in hyaluronan/cell membrane interaction and thus may provide
a deeper understanding of the complications related to their use in
ophthalmological surgery.
PMID- 9638521
TI - Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign
body giant cell formation on silane-modified surfaces in vitro. Student Research
Award in the Master's Degree Candidate Category, 24th Annual Meeting of the
Society for Biomaterials, San Diego, CA, April 22-26, 1998.
AB - A cytokine-based, in vitro model of foreign body giant cell (FBGC) formation was
utilized to examine the effect of biomaterial surface chemistry on the adhesion,
motility, and fusion of monocytes and macrophages. Human monocytes were cultured
for 10 days on 14 different silane-modified glass surfaces, during which time the
cells assumed the macrophage phenotype. The adhesion of monocytes and macrophages
during the culture period decreased by an average of approximately 50%, with the
majority of cell loss observed during days 1-3. Most important, the adhesion of
monocytes and macrophages was surface independent except for two surfaces
containing terminal methyl groups, which decreased adhesion levels. Interleukin-4
(IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were added
to the medium to induce FBGC formation and enhance macrophage adhesion,
respectively. Surprisingly, GM-CSF decreased long-term monocyte/macrophage
adhesion. IL-4-induced FBGC density was strongly influenced by the surface carbon
content, as determined by X-ray photoelectron spectroscopy (XPS). In contrast,
contact angle and surface energy displayed no correlation with FBGC formation.
The motility of adherent macrophages, as measured by time-lapse confocal
microscopy, was not affected significantly by differences in surface chemistry or
the addition of cytokines. The surface dependence of FBGC formation is
hypothesized to be the result of varying levels of silane-derived surface carbon.
PMID- 9638524
TI - Inhibition of the tissue reaction to a biodegradable biomaterial by monoclonal
antibodies to IFN-gamma.
AB - Biomaterials are increasingly used for clinical applications. However, loss of
function may occur owing to tissue reactions, which are mainly caused by a
variety of inflammatory reactions. Recently, we demonstrated that macrophages
(MO) and T cells play key roles in these reactions. Since immunological studies
showed that the T cell-derived cytokine interferon-gamma (IFN-gamma) activates
MO, the aim of this study was to investigate the possibility of modulating tissue
reactions to biodegradable biomaterials by inactivating IFN-gamma. Dermal sheep
collagen (DSC) was used as a test biomaterial. DSC impregnated with anti-IFN
gamma or phosphate-buffered saline (control) was implanted in rats. The results
showed that cellular ingrowth and formation and function of giant cells were
strongly delayed by anti-IFN-gamma. Also, MHC class II expression was strongly
inhibited. In the treated DSC, some huge giant cells were formed at the interface
but association with the DSC bundles did not occur. Finally, in both the control
and treated DSC, T cells and NK cells were rarely detected. This study
demonstrates that IFN-gamma plays an important role in the inflammatory reaction
to biomaterials. This reaction can be modulated by anti-IFN-gamma, which warrants
further studies of anti-IFN-gamma for clinical application to prevent unwanted
tissue reactions to biomaterials.
PMID- 9638527
TI - Preparation of calcium phosphate coatings on titanium implant materials by simple
chemistry.
AB - A two-step chemical treatment has been developed in our group to prepare
commercially pure titanium (cpTi) surfaces that will allow calcium phosphate (Ca
P) precipitation during immersion in a supersaturated calcification solution
(SCS) with ion concentrations of [Ca2+] = 3.10 mM and [HPO4(2-)] = 1.86 mM. It
was observed that a precalcification (Pre-Ca) procedure prior to immersion could
significantly accelerate the Ca-P deposition process. In this work, the
bioactivity of chemically treated cpTi and Ti6Al4V was further verified by
applying commercially available Hanks' balanced salt solution (HBSS), an SCS with
very low ion concentrations of [Ca2+] = 1.26 mM and [HPO4(2-)] = 0.779 mM, as the
immersion solution. It was found that a uniform and very dense apatite coating
magnesium impurities was formed if the Pre-Ca procedure was performed before
immersion, as compared with the loose Ca-P layer obtained from the abovementioned
high concentration of SCS. The formation of a microporous titanium dioxide thin
surface layer on cpTi or Ti6Al4V by the two-step chemical treatment could be the
main reason for the induction of apatite nucleation and growth from HBSS.
Variations of pH values, Ca and P concentrations, and immersion time in HBSS were
investigated to reveal the detailed process of Ca-P deposition. The described
treatments provide a simple chemical method to prepare Ca-P coatings on both cpTi
and Ti6Al4V.
PMID- 9638528
TI - Application of solubility parameter theory to dentin-bonding systems and adhesive
strength correlations.
AB - The principal aim of this study was to investigate the relationships between the
solubility parameters of ectched dentin, and adhesive primer solutions and
adhesive bond strength. Solubility parameters characterize the molecular
interactions which determine physical properties such as wetting, and thus can
serve as tools to aid development of polymeric adhesives and interpenetrating
polymer networks. If an adhesive monomer has a solubility parameter close to that
of a polymer substrate, then the monomer may act as a solvent for the polymer and
penetrate below the surface. Subsequent polymerization of the monomer may then
produce an interpenetrating network, thus adhering without necessarily forming
primary chemical bonds to the substrate. The dentin substrate considered in this
study was abraded dentin treated with ethylenediaminetetraaceitc acid. Solubility
parameters delta pr, delta h, and delta d calculated for the etched dentin
substrate were 20.3, 23.6, and 16.0 (J/cm3)1/2, respectively. Solubility
parameters of the primers were expressed using Hansen's three-dimensional scheme.
The data indicate a correlation between the calculated solubility parameters of
the etched dentin, and dentin primers and the resulting bond strengths. The
results corroborate the significance of solubility parameter considerations for
adhesive bonding to dentin.
PMID- 9638526
TI - Thermal analysis of bones from ovariectomized rats.
AB - Thermal analyses [thermogravimetry (TG) and differential thermal analysis (DTA)],
X-ray diffraction, and infrared absorption analysis of bones from ovariectomized
rats were carried out. The rats were divided into five groups: sham operated
(Sham); ovariectomized (OVX); OVX given traditional Chinese (Kampo) medicine,
Unkei-to; OVX given 17 beta-estradiol; and OVX given the estradiol vehicle,
respectively. The activation energy (delta E), a kinetic parameter from TG data
of OVX rats, increased by 57% from that in Sham rats. The administration of Unkei
to and 17 beta-estradiol to OVX rats clearly restored the delta E to the levels
of Sham rats, while the vehicle for 17 beta-estradiol had no effect. DTA data
from thermal analyses of rats from the Sham, OVX, and OVX given various compounds
were almost the same except for OVX rats given 17 beta-estradiol. The X-ray
diffraction pattern and infrared absorption spectrum of bone powders from Sham
rats were not different from those of OVX rats or others. These results strongly
suggest that kinetic parameter, delta E calculated from TG data, may be a useful
method for assessing both experimentally induced osteoporosis and drug effects on
it.
PMID- 9638530
TI - Creating molecular barriers to acute platelet deposition on damaged arteries with
reactive polyethylene glycol.
AB - We report here a novel method for blocking acute platelet deposition at the site
of vessel injury by molecularly masking thrombogenic vascular wall proteins with
covalently attached polyethylene glycol (PEG). To evaluate this technique, blood
containing 111In-labeled platelets was perfused over damaged human placental
arteries for 2 min at a wall shear rate of 200 s-1. Denuded vessel segments were
incubated for 30, 15, 5, and 1 min with a solution of either reactive PEG
diisocyanate (PEG-ISO) or nonreactive PEG-dihydroxyl (PEG-OH). Vessels treated
with PEG-ISO for 1 min exhibited 87 +/- 12% less platelet deposition (p < 0.01)
than untreated control vessels, and this reduction did not vary significantly
among treatment times, indicating that this reaction occurs rapidly enough to be
clinically applicable. To investigate the duration of this thrombotic barrier,
denuded pig carotid arteries were treated with reactive PEG-ISO for 1 min,
perfused with plasma for 30 min, and then perfused with blood containing
radiolabeled platelets. PEG-ISO-treated arteries exhibited 84 +/- 9% less
platelet deposition (p < 0.05) than untreated controls. These data demonstrate
that damaged arterial surfaces can be rendered resistant to platelet deposition
after short contact periods with reactive PEG. Molecular PEG barriers ultimately
might find application following vascular procedures to sterically inhibit blood
cell interaction with damaged vascular surfaces.
PMID- 9638529
TI - Development of a novel osteochondral graft for cartilage repair.
AB - This study reports the development of a novel osteochondral graft for cartilage
repair. A technique of proteoglycan extraction via timed enzymatic digestion with
hyaluronidase and trypsin and subsequent processing with a chloroform-methanol
solution to remove cellular debris from a fresh-frozen bovine osteochondral
sample is a method described to prepare a stable biological carrier of low
immunogenicity. Lyophilization of the carrier followed by rehydration in a
suspension of lapine chondrocytes produced a chimeric xenograft that succeeded in
vivo in enhancing cartilage repair. In a pilot study, full-thickness articular
cartilage defects treated with these xenografts demonstrated improved healing
compared to untreated defects or defects treated with unseeded grafts at 2, 6,
and 12 weeks postimplantation. The xenograft provoked a mild inflammatory
response; however this did not impede the repair process. Further investigation
of this novel chimeric xenograft eventually may yield a method of cartilage
repair superior to current methods of treatment.
PMID- 9638531
TI - Effects of polyelectrolyte complex (PEC) on human periodontal ligament fibroblast
(HPLF) function. I. Three-dimensional structure of HPLF cultured on PEC.
AB - Human periodontal ligament fibroblast (HPLF) cultured on tissue culture dishes
(TCD), irrespective of the presence of serum, showed only a spreading form. In
contrast, using polyelectrolyte complex (PEC) as a matrix, HPLF showed spreading,
round, and aggregate forms. Cells of the inner part of the aggregate contacted
with each other to form a three-dimensional structure, and this condition
corresponded to typical tissues in vivo. These seemed to be related to the
interrelation between growth and morphology; that is, the HPLF of the spreading
form was considered to belong to a proliferation phase, and the HPLF of the round
and aggregate forms, with a little growth, seemed to belong to a functional phase
of the cell cycle, indicating that PEC is able to control such cell functions as
proliferation, morphology, and differentiation. The cell aggregate was observed
only on PEC with carboxymethyl residues and was stained by alizarin red (AR),
which suggested mineralization. The spreading cells on PEC containing sulfate
residues were not stained by AR. Therefore, it was found that there was a certain
relationship between cell growth and morphology, and that PEC affected the cell
cycle and promoted proliferation and differentiation of HPLF.
PMID- 9638522
TI - In vitro formation by reverse dialysis of collagen gels containing highly
oriented arrays of fibrils.
AB - Acid extracts of rat tail tendon were subjected to reverse dialysis against 0.5%
PEG at 4 degrees C in an attempt to induce liquid crystallization. After 48 h,
gel and fibril formation were initiated by continuing dialysis at 20 degrees C
against the same PEG solution adjusted to pH 7.4. The inclusion of calcium- or
magnesium chloride (final concentration 0.3-33 mM) in the collagen solution
before dialysis resulted in strongly birefringent gels that showed a progressive
rotation of the slow axis of birefringence with increasing distance from the
lateral margin of the gel. The gels contained fibers running predominantly in the
plane of the flattened gel and crossing at angles of between 55 degrees and 90
degrees. We suggest that liquid crystallization is responsible for this
phenomenon and that it might be possible to exploit this to produce materials for
tissue engineering.
PMID- 9638534
TI - X-ray diffraction and polarizing optical microscopy investigation of the
structural organization of rabbit tibia.
AB - X-ray diffraction and polarized optical microscopy investigations were carried
out on thin sections of rabbit tibia in order to study the morphological
organization of the structural components of this tissue, which often is utilized
to test bone response to implants. In the optical microscope, the lateral face as
well as the lateral portion of the caudal face exhibit a lamellar structure with
an alternation of dark and bright lamellae running parallel to the long axis of
the tibia. In contrast, both in the medial face and in the medial portion of the
caudal face there are numerous osteonic structures. In spite of the complexity of
this morphological organization, the results of small- and high-angle X-ray
diffraction analyses indicate that the structural relationship between collagen
fibrils and inorganic crystals is quite similar to that observed in single
osteons and allows evaluation of the orientation of the two main structural
components. Both collagen fibrils and apatitic crystallites are preferentially
oriented parallel to the long axis of the tibia. The degree of orientation is
greater in the thickness than in the plane of the lamellae, suggesting that
collagen fibrils and inorganic crystallites lie preferentially in the plane of
the lamellae, where they follow an oblique course. The degree of orientation of
the apatitic crystallites is higher in the lateral face than in the medial and
caudal faces, in agreement with the optical microscopic images. The results
provide information that must be taken into account when evaluating the
structural modifications of bone due to the insertion of a prosthetic device.
PMID- 9638532
TI - Effects of polyelectrolyte complex (PEC) on human periodontal ligament fibroblast
(HPLF) function. II. Enhancement of HPLF differentiation and aggregation on PEC
by L-ascorbic acid and dexamethasone.
AB - In addition to many types of extra cellular matrix (ECM) in vivo, cells are
stimulated by many types of vitamins, hormones, growth factors, etc. In this
paper the effects of L-ascorbic acid 2-phosphate (Asc-2P) and dexamethasone (Dex)
on proliferation and differentiation of human periodontal ligament fibroblast
(HPLF) using polyelectrolyte complex (PEC) as a matrix in vitro will be
discussed. The PEC was composed of chitosan as a polycation, with carboxymethyl
(CPEC) or sulfated chitin (SPEC). Asc-2P (0.2 mM) inhibited the growth of HPLF on
CPEC, but promoted the growth on SPEC. Moreover, the aggregation of HPLF on CPEC
was inhibited by Asc-2P, but that on SPEC was induced in the presence of Asc-2P
and Dex. Although Asc-2P reduced an increase in alkaline phosphatase (ALPase)
activity of HPLF on CPEC as well, it induced a twofold increase in ALPase
activities on SPEC and TCD. Furthermore, in the medium containing Asc-2P and 100
mM of Dex, cell growth was inhibited, but ALPase activity was promoted on both
SPEC and TCD to form many aggregates on SPEC. ALPase activity increased by
twofold over that of HPLF cultured in the medium containing only Asc-2P.
Therefore, it is suggested that the cell functions of HPLF are controlled by the
combination of PEC and additives.
PMID- 9638533
TI - Modification of glassy carbon surfaces with synthetic laminin-derived peptides
for nerve cell attachment and neurite growth.
AB - Interactions between cultured nerve cells and surfaces are of importance for the
implantation of biocompatible electrode materials such as glassy carbon (GC).
Since implants serve as recording sensors in prosthetic neuroscience, we
investigated whether coating electrodes with certain laminin derivatives
containing the peptide sequences SIKVAV, CDPGYIGSR, PDSGR, YFQRYLI, and
RNIAEIIKDA influences neuronal adhesion and neurite outgrowth in vitro. The
coating of GC was performed by electrochemical polymerization and, for
comparison, by adsorption or covalent coupling. Electrochemical polymerization is
suitable for the coupling of peptides to GC, as shown by amino acid analysis and
sequencing. Embryonic chicken retinal ganglion cells and brain cells (days E7 or
E17) were used for both attachment and growth studies. Surfaces made by
electrochemical polymerization of peptides were more efficient than those made by
adsorption or covalent coupling of peptides. Synthetic cyclic peptide derivatives
of CDPGYIGSR and 18-mer SIKVAV were found to be more efficient than the linear
peptides. Competitive effects that resulted in a decreased cell attachment could
be found upon application of soluble peptides. Nevertheless, irrespective of the
method of coating, peptides were less efficient compared with the whole laminin
molecule, as expected from its multiple adhesion sites. When small GC pins were
implanted into the brain of E17 chicken after coating with the 18-mer SIKVAV
peptide, nerve cell attachment was observed in vivo. The results suggest that
chronically implantable materials may exert a higher neurocompatibility when
coated with synthetic peptides.
PMID- 9638536
TI - Platelet adhesion onto wettability gradient surfaces in the absence and presence
of plasma proteins.
AB - A wettability gradient was prepared on lowdensity polyethylene (PE) sheets by
treating them in air with a corona from a knife-type electrode the power of which
increased gradually along the sample length. The PE surfaces oxidized gradually
with the increasing corona power and a wettability gradient was created on the
surfaces, as evidenced by the measurement of water contact angles, Fourier
transform infrared spectroscopy in the attenuated total reflectance mode, and
electron spectroscopy for chemical analysis. The wettability gradient surfaces
prepared were used to investigate the adhesion behavior of platelets in the
absence and presence of plasma proteins in terms of the surface
hydrophilicity/hydrophobicity of polymeric materials. The platelets adhered to
the wettability gradient surfaces along the sample length were counted and
examined by scanning electron microscopy (SEM). It was observed that the platelet
adhesion in the absence of plasma proteins increased gradually as the surface
wettability increased along the sample length. The platelets adhered to the
hydrophilic positions of the gradient surface also were more activated (possessed
more pseudo pods as examined by SEM) than on the more hydrophobic ones. However,
platelet adhesion in the presence of plasma proteins decreased gradually with the
increasing surface wettability; the platelets adhered to the surface also were
more activated on the hydrophobic positions of the gradient surface. This result
is closely related to plasma protein adsorption on the surface. Plasma protein
adsorption on the wettability gradient surface increased with the increasing
surface wettability. More plasma protein adsorption on the hydrophilic positions
of the gradient surface caused less platelet adhesion, probably due to platelet
adhesion inhibiting proteins, such as high-molecular-weight kininogen, which
preferably adsorbs onto the surface by the so-called Vroman effect. It seems that
both the presence of plasma proteins and surface wettability play important roles
for platelet adhesion and activation.
PMID- 9638538
TI - Engineering smooth muscle tissue with a predefined structure.
AB - Nonwoven meshes of polyglycolic acid (PGA) fibers are attractive synthetic
extracellular matrices (ECMs) for tissue engineering and have been used to
engineer many types of tissues. However, these synthetic ECMs lack structural
stability and often cannot maintain their original structure during tissue
development. This makes it difficult to design an engineered tissue with a
predefined configuration and dimensions. In this study, we investigated the
ability of PGA fiber-based matrices bonded at their fiber crosspoints with a
secondary polymer, poly-L-lactic acid (PLLA), to resist cellular contractile
forces and maintain their predefined structure during the process of smooth
muscle (SM) tissue development in vitro. Physically bonded PGA matrices exhibited
a 10- to 35-fold increase in the compressive modulus over unbonded PGA matrices,
depending on the mass of PLLA utilized to bond the PGA matrices. In addition, the
bonded PGA matrices degraded much more slowly than the unbonded matrices. The
PLLA bonding of PGA matrices had no effect on the ability of cells to adhere to
the matrices. After 7 weeks in culture, the bonded matrices maintained 101 +/- 4%
of their initial volume and an approximate original shape while the unbonded
matrices contracted to 5 +/- 1% of their initial volume with an extreme change in
their shape. At this time the bonded PGA matrices had a high cellularity, with
smooth muscle cells (SMCs) and ECM proteins produced by these cells (e.g.,
elastin) filling the pores between PGA fibers. This study demonstrated that
physically bonded PGA fiber-based matrices allow the maintenance of the
configuration and dimensions of the original matrices and the development of a
new tissue in a predefined three-dimensional structure. This approach may be
useful for engineering a variety of tissues of various structures and shapes, and
our study demonstrates the importance of matching both the initial mechanical
properties and the degradation rate of a matrix to the specific tissue one is
engineering.
PMID- 9638541
TI - Cost of diabetes-related amputations in minorities.
AB - The objective of this study was to identify the direct cost and length of
hospitalization of diabetes-related lower extremity amputations among Hispanics,
African Americans, non-Hispanic whites, and Asians. The authors used a database
from the office of Statewide Planning and Development in California that
identified all hospitalizations for lower extremity amputations in the state in
1991. Amputation level was defined by the ICD-9-CM codes 84.11-84.18. The total
hospital charges for diabetes-related lower extremity amputations for the state
of California in 1991 was $141 million. The mean hospital charge (HC) per patient
with all ethnic groups combined was $27,930; and the mean length of stay (LOS)
was 15.9 days. African Americans had significantly higher mean charges ($32,383)
and longer stays (17.3 days) compared to all other ethnic groups (p < .05). Toe
level amputations had lower HC (p < .05) and LOS (p < .01) than other amputation
levels for all race groups. One-quarter of the population received multiple
amputations during their hospital stay. These patients incurred significantly
higher hospital charges ($44,731) and stayed in the hospital longer (23.4 days)
than those receiving only a single amputation. There was a considerable variation
in the HC and LOS among ethnic groups by level of amputation. The direct charges
reported in this study suggest considerably higher overall direct costs than have
been previously reported in the medical literature. The greater burden of disease
experienced by African Americans is probably related to their higher amputation
cost and longer hospitalization.
PMID- 9638540
TI - Functional outcome in the elderly following lower extremity amputation.
AB - Data regarding functional outcome in the elderly following major lower extremity
amputation (LEA) are minimal. In the general diabetic population there is a
significant mortality associated with these procedures, with the 5-year survival
rates approaching only 40%. Contrasts between this group and the nondiabetic
population will help to clarify the morbidity of these procedures and
substantiate efforts at limb salvage. The authors review their experience with
patients 80 years of age and above undergoing major LEA between 1990 and 1995
with a specific focus on postoperative mortality and functional status. Forty-one
patients were studied, 67% of whom had diabetes mellitus. Postoperative
functional status remained unchanged in 40% and worsened in 55% of patients,
while residential status was unchanged in 68% and worsened in 32%. The median
survival for patients with and without diabetes was 19 and 49 months,
respectively. The 5-year survival for the entire group was 25% and was not
statistically different in the two subgroups. The authors conclude that major LEA
in the very elderly is associated with a considerable mortality and deterioration
of functional and residential status.
PMID- 9638539
TI - Complement activation and inflammation triggered by model biomaterial surfaces.
AB - Biomaterial-mediated complement activation repeatedly has been invoked as a
trigger of phagocyte reactions and inflammation. However, a direct correlation
between complement activation and inflammatory responses to biomaterial surfaces
has yet to be established. Using an animal implantation model and gold surfaces
bearing various thiol-linked functionalities, we investigated the potency of
different surface groups in prompting complement activation in vitro and surface
mediated accumulation of inflammatory cells in vivo. Among the surfaces tested,
mercaptoglycerol- and mercaptoethanol-bearing surfaces engendered the strongest
inflammatory responses, as reflected by the accumulation of large numbers of
adherent neutrophils and monocytes/macrophages. In contrast, L-cysteine-coated
surfaces caused only minor inflammatory responses, and both glutathione-modified
and untreated gold implants attracted minimal numbers of inflammatory cells. The
accumulation of inflammatory cells on mercaptoglycerol surfaces appears to arise
from surface-mediated complement activation because complement-depleted animals
failed to exhibit inflammatory responses to mercaptoglycerol-modified implants.
Furthermore, there is a close relationship between surface-mediated complement
activation (as measured by in vitro iC3b/C5b-9 generation and C3 deposition) and
in vivo inflammatory responses. At least in this animal model and with these
model surfaces, our results indicate that surface-mediated complement activation
can be responsible for the subsequent accumulation of inflammatory cells on
implant surfaces.
PMID- 9638535
TI - Differences in microstructural characteristics of dense HA and HA coating.
AB - Two implant types of hydroxyapatite (HA) currently are available for dental
implants: dense HA-cemented titanium (Ti) and HA-coated. It has been shown in
previous reports that there are differences in the chemical and mechanical
stabilities between the dense HA and HA coated. The differences are thought to be
due to structural differences between the two ceramic types. The aim of this
study was to investigate the differences in microstructural characteristics of
currently available dense HA and HA coated implants before implantation and at
periods of 3 weeks and 10 months after implantation in canine bone. X-ray
diffractometry, infrared analysis, transmission electron microscopy, and energy
dispersive X-ray analysis were used. The dense HA is composed of crystal grains,
with a well crystallized structure of HA, closely bound to each other and
approximately 0.4-0.6 micron in size. Implantation did not change the original
sintered structure of the dense HA. The HA coating was composed of an amorphous
phase with a Ca/P ratio of 1.46 and a crystal phase consisting of
oxyhydroxyapatite, tricalcium phosphate, tetracalcium phosphate, and CaO, with a
Ca/P ratio of 1.57. In the amorphous phase, compared to other portions in the
amorphous phase, there were some layers with lower atomic density and with no
significant difference in Ca/P ratio. After implantation, the crystallization of
super fine crystals of approximately 4-5 nm in thickness occurred in the
amorphous phase, and with time it progressed and spread from the surface to the
deeper portion of the HA coating. A Ca/P ratio of 1.58 in the crystallized
portion was close to the ratio (1.60) in the dense HA, suggesting that the super
fine crystals were HA. This crystallization cannot significantly decrease the
solubility of the amorphous phase portion and poses risks of stress accumulation
within the coating and a decrease of binding strength between the HA coating and
the substrate.
PMID- 9638542
TI - Beneficial effects of electrical stimulation on neuropathic symptoms in diabetes
patients.
AB - Transcutaneous electrical nerve stimulation is utilized for relieving pain in the
diabetes peripheral neuropathy. Previous studies were short-term and did not
document sustained beneficial effects. In this study, the authors evaluated long
term effectiveness of electrotherapy administered by proprietary equipment, an H
wave machine. A detailed questionnaire concerning patients' symptoms prior to and
following electrotherapy was mailed to the users of H-wave machine. The responses
of 34 individuals who had diabetes mellitus were analyzed (age 74.1 +/- 1.6 SEM
years, body mass index 28.5 +/- 0.8 kg/m2, duration of diabetes 15.8 +/- 2.0
years and duration of neuropathic symptoms 8.0 +/- 1.8 years). Telephone
interviews were conducted with 20 additional diabetes patients selected randomly
from the persons who did not return the questionnaire. Forty-one (76%) patients
reported a 44.0 +/- 4.0% subjective improvement in their neuropathic pain. The
overall improvement in pain was also significant on an analog scale of 10 (p <
.01), and correlated well with the percent amelioration data (r2 = .65). These
data suggest an effectiveness of electrotherapy in managing neuropathic pain as
an adjunct to the analgesics. It appears to provide continued benefit as the
responders have used this nonpharmacological treatment modality for an average
period of 1.7 +/- 0.3 years.
PMID- 9638543
TI - The effects of diabetes mellitus on the material properties of human metatarsal
bones.
AB - While some investigations have focused on the effect of diabetes on the material
properties of connective tissue in both the human and animal model, no study to
date has investigated the effects of the disease process on human metatarsal
bones. This investigation compared the material properties of human metatarsal
bones from young diabetic donors (51.3 +/- 8 years) and older nondiabetic donors
(72.3 +/- 10 years). The results demonstrated no significant differences between
the two groups. This would seem to suggest that the effects of aging are
comparable to the effects of diabetes on the structural integrity of human
metatarsal bones.
PMID- 9638537
TI - Flow cytometric assays to detect platelet activation and aggregation in device
implanted calves.
AB - Cardiovascular device development often relies upon large-animal models to assess
blood biocompatibility prior to initiating clinical trials. Unfortunately, the
amount of information gleaned from such trials is limited by simple assays that
do not take full advantage of immunotechnological advances that increasingly are
applied in clinical studies. Thus we have developed and tested new flow
cytometric techniques for measuring circulating activated bovine platelets and
platelet microaggregates. Monoclonal antibodies (MAbs) raised against both
activated and quiescent bovine platelets were incubated with control and PMA-or
ADP-stimulated whole blood. Selected MAbs detected activated bovine platelets and
platelet microaggregates in vitro with flow cytometry. Five calves implanted with
one of two designs of nonpulsatile ventricular-assist devices (VADs) were
followed with these assays prior to and during VAD implantation. Circulating
activated bovine platelets and microaggregates increased after implantation in
all animals and, alternatively, remained elevated or returned toward preimplant
levels. Platelet activation percentages as detected temporally by three MAbs were
correlated with one another, and platelet activation was correlated with
microaggregate formation. In summary, these new methods for the sensitive
measurement of circulating activated bovine platelets and microaggregates may
provide valuable information for the development and assessment of future
cardiovascular device designs.
PMID- 9638545
TI - Reconstruction of hallux limitus deformity using a first metatarsal sagittal-Z
osteotomy.
AB - A sagittal-Z osteotomy was used for reconstruction of symptomatic grade I and
grade II hallux limitus deformity in 10 patients using the Regnauld
classification system. This surgical method was also used in a patient to
reconstruct a structurally elevated first metatarsal as an adverse sequela of
previous hallux valgus surgery. All patients exhibited evidence of radiographic
metatarsus primus elevatus (MPE) and/or an anatomically elongated first
metatarsal (EM). Linear comparison of first and second metatarsal length was
performed in the transverse plane on dorsoplantar weightbearing radiographs. A
long first metatarsal (positive metatarsal protrusion distance) was considered an
anatomically elongated metatarsal. Metatarsus primus elevatus was evaluated by
comparing the dorsal cortical margin of the first and second metatarsals and/or
comparing the first metatarsal-cuneiform joint axis with the talonavicular joint
axis. Metatarsus primus elevatus was therefore defined as a position of the
dorsal cortical margin of the first metatarsal 5 mm superior to that of the
second. A dorsal position of the first metatarsal-cuneiform joint axis in
relation to the talonavicular joint axis also established MPE. A total of 11
patients underwent a total of 13 procedures. There were eight excellent results
(73%) and three good results (27%). There were no fair or poor results.
PMID- 9638546
TI - Retrospective analysis of the Mau osteotomy and effect of a fibular
sesamoidectomy.
AB - The purpose of this study was to evaluate retrospectively outcomes of the Mau
osteotomy for hallux abducto valgus deformity. Twenty-two patients were evaluated
by the senior author on an average of 14 months (range, 3-34 months) following
their surgery. Preoperative and postoperative intermetatarsal (IM) and hallux
abductus (HA) angles were evaluated as well as range of motion of the first
metatarsophalangeal joint and patient satisfaction. The mean preoperative IM and
HA angles were 16.1 degrees and 35.8 degrees. The mean reduction in IM and HA
angles was 10.5 degrees and 23.5 degrees, respectively. Joint range of motion was
58 degrees of dorsiflexion (range, 42 degrees-80 degrees) and 11 degrees of
plantarflexion (range, 0 degree-20 degrees). There were no cases of delayed
healing or avascular necrosis. There were two patients (9%) with radiographic
values consistent with hallux varus; however, neither patient had a clinical
appearance of hallux varus and neither patient was displeased with the outcome.
Ninety-one percent of patients returned to a soft shoe or sneakers in an average
of 5.1 weeks following surgery. Eighty-two percent of patients had no pain at the
time of their evaluation, and 96% of patients stated they were satisfied or very
satisfied with the surgery. Comparing the subgroup of patients who underwent a
Mau-Reverdin procedure with another subgroup undergoing a Mau-Reverdin fibular
sesamoidectomy, there was a 3.7 degrees greater reduction of IM angle and 6.7
degrees greater reduction in HA angle in the subgroup with the fibular
sesamoidectomy.
PMID- 9638544
TI - Talocalcaneal bar resection.
AB - The purpose of this retrospective study is to report the author's experience with
talocalcaneal bar resections in eight young patients, mean age 14.1 years, with a
mean follow-up of 54 months (range, 36-136 months). All patients were submitted
before surgery to conservative treatment during 20.3 months (range, 6-60 months)
which consisted of nonsteroidal anti-inflammatory medication, physical therapy,
short waves, and insoles. At follow-up, no recurrence and no secondary deformity
of the foot were observed. Four patients were totally pain free with no
restriction of activity, two patients had some pain during sport exercises, and
one patient with bilateral involvement had pain after strenuous activities. The
study evaluated the mobility of the subtalar joint at follow-up by comparing it
with the healthy side. A total restoration of mobility was observed in four
patients, partial in three, and limited residual mobility was observed in only
one patient. Talocalcaneal bar resection is the treatment of choice in young
patients after failure of conservative measures. In this population, there is no
place for subtalar joint arthrodesis.
PMID- 9638547
TI - Stabilization of the subluxed second metatarsophalangeal joint: flexor tendon
transfer versus primary repair of the plantar plate.
AB - Surgical treatment of the subluxed second metatarsophalangeal joint (MTPJ) has
been a consistently frustrating problem for the foot and ankle surgeon. The
plantar plate is the principal stabilizing structure of the second MTPJ and
compromise to its integrity has been implicated as the cause of the subluxed
second toe. Flexor tendon transfer has been reported as the mainstay of treatment
to stabilize the subluxed second MTPJ. Recently, primary repair of the plantar
plate has been advocated, yet no research exists comparing it to flexor tendon
transfer. Eight freshly frozen lower extremity cadaver specimens were mounted on
a custom-fabricated load frame. A vertical dorsally directed force was applied to
the base of the proximal phalanx of the second toe via a pneumatic actuator to
stimulate the Lachman test. Dorsal displacements of the proximal phalanx were
measured with a linear variable distance transducer. This investigation examined
the comparative strength of flexor tendon transfer versus primary repair of the
plantar plate in stabilizing the second MTPJ. Results showed a significant
difference between the transected plantar plate and the intact plantar plate.
Displacements for the repair groups were similar to the intact plantar plate
group and also significantly different from the transected plantar plate. Primary
repair of the plantar plate is a viable alternative to flexor tendon transfer in
stabilizing the second MTPJ with the advantage of addressing the pathology
anatomically. Clinical studies are needed to substantiate these laboratory
findings.
PMID- 9638548
TI - A comparison of the efficacy of injectable dexamethasone sodium phosphate versus
placebo in postoperative podiatric analgesia.
AB - Forty-two patients undergoing identical bilateral foot surgery were evaluated in
a double-blind study designed to evaluate the efficacy of injectable
dexamethasone sodium phosphate versus placebo as an analgesic. Patients who had
elective foot surgery on an outpatient basis received an injection of
dexamethasone sodium phosphate in one foot and an equivalent injection of normal
sterile saline in the contralateral foot. Both the patients and the surgeons were
unaware of which foot was injected with each agent. The results suggest that
there was not a difference in the patient perception of which foot was most
painful. Forty-eight to 72 hours after surgery, 18 (44%) patients identified the
foot that received steroid as less painful, 18 (44%) patients identified the foot
that received placebo as less painful, and 5 (12%) patients did not perceive a
difference. In addition, there was not a difference in outcome based on soft
tissue or osseous procedures.
PMID- 9638549
TI - Autogenous free dermal fat grafts in the surgical approach to plantar
fibromatosis.
AB - Plantar fibromatosis is a benign disorder of the foot in which there is fibrous
tissue infiltration of the plantar aponeurosis and in some cases the overlying
skin. Treatment is indicated for pain and functional gait disturbance. Even with
wide fascial resection, recurrence with spreading, scarring, and continued
discomfort can be a frustrating and difficult problem. Various techniques to
lessen recurrence have included split-thickness skin grafting and Marlex mesh
placement. However, these procedures have documented problems, including
recurrence, foreign-body reaction, scarring, and inadequate soft-tissue coverage.
The authors introduce dermal fat grafting following primary excision as a means
to minimize recurrence while maintaining the anatomic architecture of the foot
and preserving a soft, supple weightbearing surface with minimal scar tissue
formation.
PMID- 9638550
TI - Angiomatoid malignant fibrous histiocytoma: report of an unusual case with highly
aggressive clinical course.
AB - The authors report a case of angiomatoid malignant fibrous histiocytoma (AMFH),
affecting a 9-year-old girl, with a highly aggressive clinical course. The tumor,
noticed by the patient as a painless nodule in the dorsum of her left foot for 12
months, recurred 8 months after initial excision, and despite wide local
reexcision, metastasized 4 months later to the liver and lung, where it grew at
an alarming rate, to the extent of occupying the entire left hemithorax in a
period of 10 weeks and killed the patient 14 months after initial excision.
Review of the literature showed that the culminated rates of recurrence,
metastasis, and mortality for AMFH were 23.2%, 8.7%, and 4.3%, respectively,
indicating that it is definitely a malignant neoplasm with a potentially fatal
outcome.
PMID- 9638552
TI - Diabetic foot infections.
PMID- 9638551
TI - Lateral subtalar dislocation: review of the literature and case presentation.
AB - Lateral subtalar joint dislocations are rare injuries which are usually the
result of a violent eversional force, driving the talar head medially and
displacing the rest of the foot laterally. Associated fractures and obstruction
to closed reduction are more common with lateral than medial dislocations.
Avascular necrosis of the talus and navicular as well as subtalar instability may
result from these injuries. Severe post-traumatic subtalar arthritis may warrant
triple arthrodesis. Prompt closed reduction of lateral subtalar dislocation is
recommended to avoid soft-tissue or neurovascular compromise. A short period of
immobilization limits loss of subtalar range of motion. Open reduction may be
required, particularly with entrapment of the posterior tibial tendon or
obstructing fracture fragments. A case of lateral subtalar joint dislocation is
presented.
PMID- 9638553
TI - The simple "plumb line" osteotomy guide.
PMID- 9638556
TI - Sketching the framework for a history and sociology of homosexualities in the
Nordic countries.
PMID- 9638554
TI - Flexor hallucis longus dysfunction.
PMID- 9638557
TI - State policy, popular discourse, and the silence on homosexual acts in early
modern Sweden.
AB - In Sweden, homosexual acts between men were mentioned in secular law for the
first time in 1608. Despite the explicit criminalization, very few trials are
known from the seventeenth and eighteenth centuries, and the new National Law
Code of 1734 contained no sanction at all. The central issue of this essay is how
the insignificant number of court cases and the seemingly very limited judicial
interest in the issue of sodomy in Early Modern Sweden should be interpreted. The
silence of the new law is explained by a shift in the official policy from
deterrence to a policy of silence, but the low number of court cases was foremost
dependent on a lacking actualization and problematization of homosexual acts in
the Swedish popular discourse on sexuality, gender, and prestige. Finally, it is
argued that this undeveloped popular discourse probably also corresponded to a
meagre and rather restricted sexual practice.
PMID- 9638558
TI - A premodern legacy: the "easy" criminalization of homosexual acts between women
in the Finnish Penal Code of 1889.
AB - Homosexual acts between women were criminalized in Finland in the 1889 Penal Code
which also criminalized men's homosexual acts for the first time explicitly in
Finnish legislation. The inclusion of women in the Penal Code took place without
much ado. In the article it is argued that the uncomplicated juxtaposing of men
and women was due to the legacy of a cultural pattern where man and woman, as
categories, were not in an all-pervasive polarity to each other, for example, in
sexual subjectivity. A cultural pattern of low gender polarization was typical of
preindustrial rural culture, and it can help us apprehend also certain other
features in contemporary Finnish social and political life, for example, women
obtaining a general franchise and eligibility for the parliament first in the
world, in 1906. A modern image of "public man" and "private woman" was only
making its way in Finnish society; hence, there was not much anxiety at women's
entry in politics, or, for that matter, at their potential for (homo)sexual
subjectivity becoming recognized publicly in criminal law.
PMID- 9638559
TI - Creating their own private and public: the male homosexual life space in a Nordic
city during high modernity.
AB - In this article I describe the male homosexual life space in a Nordic city during
the decades around the Second World War. It consisted almost entirely of outdoor
places such as parks, public conveniencies, and streets. It included, in Delph's
(1978) words, not only erotic, but also cultural and social oases, fostering an
extensive and varied social life and a growing community. Most of this outdoor
space was invisible to those other than the participants. It had its own
differentiation of, and meanings for, "public" and "private." A poor economy,
overcrowding, and the classical modern city helped shape the location and design
of the male homosexual life space, as did the participation of many men who did
not look upon themselves as "homosexual." During this period, and especially
after the Second World War, this life space began to change in a direction
pointing towards that of today, that is, towards less outdoor life and more life
in homes and semipublic indoor spaces. Better economy, the rise of the welfare
state, and diminished overcrowding furthered this movement. Among other things,
these changes stimulated the withdrawal of men who did not see themselves as
"homosexual." The transformation of the city into the spread out, suburbanized
city, with segregation of various functions, contributed to the development, as
did the obstruction of parks and toilets as meeting places by public authorities.
The law reform of 1944, which decriminalized homosexual erotic acts between
adults, was also of importance.
PMID- 9638560
TI - The power of confession: the role of the criminal law and courtpractices in the
production of knowledge concerning sexuality between women: Finland, in the
1950s.
AB - The article discusses a number of court cases on women's same-sex fornication in
the Finnish countryside in the 1950s. Based on a close reading of the minutes of
the police investigations and the court records, the article shows how the notion
of sexual acts between women, and the notion of certain modes of conduct as
"sexual," were constructed in these proceedings. The authorities could conceive
sexual relations only in terms of the "heterosexual matrix" (cf. Judith Butler);
hence they assumed that the alleged sexual encounters between the women were a
copy of a heterosexual sexual intercourse. As for the accused women, many of whom
were connected with a Christian sect, they often insisted that the physical
expressions of their mutual affection were not sexual, and they opposed the
interpretation that their conduct might have anything to do with homosexuality,
which they considered a pathology. As the women nevertheless often ended up
repenting their conduct, they reproduced the conventional image of sexually
passive "soft" woman, though perhaps partly because of strategic reasons.
PMID- 9638561
TI - A dung beetle in distress: Hans Christian Andersen meets Karl Maria Kertbeny,
Geneva, 1860: some notes on the archaeology of homosexuality and the importance
of tuning.
AB - In 1860, the Danish fairy tale writer (whose fairy tales are perhaps primarily
for grown-ups) met Karl Maria Kertbeny--who is supposed to have coined the term
"homosexual" (first used in a private manuscript in 1868). The meeting caused
immense despair in Andersen; yet what happened has remained a mystery. A careful
study of Andersen's fairy tales and papers, however, provides a clue to an
answer. The article deals with the horrors of being labelled; but it also
discusses labelling as merely a minor part of what goes on in the making of the
modern homosexual. Above all, Andersen's moods seem important and identifiable to
us as homosexuals; more generally, they seem stirringly close to postmodern
existence.
PMID- 9638562
TI - Identity, place, and erotic community within gay leather culture in Stockholm.
AB - There has been much recent attention to the relationship between the construction
of place, identity, and the body. This paper examines some of these themes in a
presentation of the gay leather scene in Stockholm, Sweden. Based on ethnography
of Stockholm's only true leather club, it shows how identity and spatial location
are implicated in one another. It also looks at social and cultural processes of
containment and dispersion within leather culture, the creation of erotic bodies,
and forms of erotic interaction. These processes are seen as reflecting features
of the wider Swedish gay scene and society in general, which is sometimes less
tolerant than it is imagined to be. Aspects of current and possible future
transformations of leather culture and style are also briefly considered.
PMID- 9638563
TI - Dressing up in power: Tom of Finland and gay male body politics.
AB - On one hand, the article examines ways in which Tom of Finland's drawings
participated in discursive formations that created and disseminated the gay macho
look. "Tom's men" appropriated these pictures to make gay identities visible in
their bodies, and created potentially resisting meanings. On the other hand, the
author explores the meanings of Tom's drawings, particularly in relation to
discourses of sexuality, gender, and race. He argues for the multiplicity of
power and for ambivalent interaction of resistance and oppression in Tom's
drawings. Tom's pictures draw attention to an idea, derived from Michel Foucault,
that power and resistance are to be found in one and the same place. Although
ways in which these images are used may give rise to subversive meanings they
also circulate racist, sexist, and fascist discourses that contradict their
potentially radical meanings. Indeed, the problem with the transgressive
pleasures is that transgression may help to sustain the limits that are supposed
to be crossed and deconstructed by a transgressor.
PMID- 9638564
TI - The ambiguity of lesbian and gay marriages: change and continuity in the symbolic
order.
AB - The article discusses the Registered Partnership Act, passed in Norway in 1993,
which has given gay and lesbian couples a right to register their relationship
and to obtain many of the legal rights that heterosexual couples have. The
article argues that the introduction of the Act is a product of, among others,
cohabitation having become more legitimate as a life-form also among
heterosexuals. The practical consequences of the Act have been modest, with
relatively few couples having registered their relationship. The article suggests
that the symbolic rather than the practical aspects of the Act have been
important, and even then, the symbolic effect of the Act is equivocal. The new
formal rights of gays and lesbians are of decreasing social and symbolic value,
as new boundaries for legitimate life-forms are being demarcated elsewhere: While
legislation on marriage concedes that personal relationships are a private
matter, the right to have and to foster children is regarded as an issue where
society at large should have a say. This view is also reflected in the
restrictions that the Registered Partnership Act has placed on gay and lesbian
couples in having children of their own.
PMID- 9638565
TI - Gay and lesbian politics: assimilation or subversion: a Danish perspective.
AB - The article discusses the trajectory of lesbian and gay politics in Denmark, from
the 1970s to the 1990s. It argues that, as part of the social and cultural
change, marriage has become an empty institution; hence the ostensibly remarkable
progress that gay and lesbian couples have also been conceded a marriage-like
status. However, while pursuing this right, lesbian and gay organizations may
have been too compliant with middle-class ideals of "decent" lifestyles; entering
a registered partnership may become a new norm which excludes "less respectable"
modes of homosexual lifestyles. The radical potential of homosexuality as a
manifestation of the variety of lifestyles should not be jettisoned in the name
of politics of assimilation.
PMID- 9638566
TI - The ethics of care: a feminist virtue ethics of care for healthcare
practitioners.
AB - In this paper I seek to distinguish a feminist virtue ethics of care from (1)
justice ethics, (2) narrative ethics, (3) care ethics and (4) virtue ethics. I
also connect this contemporary discussion of what makes a virtue ethics of care
feminist to eighteenth and nineteenth century debates about male, female, and
human virtue. In conclude that by focusing on issues related to gender--primarily
those related to the systems, structures, and ideologies that create and sustain
patterns of male domination and female subordination--we can begin to appreciate
that true care and bona-fide virtue can flourish only in societies that treat all
persons with equal respect and consideration.
PMID- 9638567
TI - Impartial principle and moral context: securing a place for the particular in
ethical theory.
AB - This essay critically assesses two strategies of accommodation used by defenders
of impartialism in ethics to argue that the care orientation represents no
genuine challenge to impartialist theoretical paradigms. One strategy focuses on
impartiality as a constraint on moral deliberation, the other as a constraint on
moral justification. While highlighting respects in which the commitment to
impartiality is more consonant with the care orientation than many advocates of
care have acknowledged, this essay attempts to clarify crucial ways in which each
accommodationist strategy fails, thus locating some of the more important
contributions and challenges the care orientation offers to moral theory.
PMID- 9638568
TI - Care theory and the ideal of neutrality in public moral discourse.
AB - In this paper I argue that Care theory has the resources to offer an insightful
and original theoretical perspective on issues in medical ethics. The paper
begins with a discussion of the sort of theory Care is, and argues that it
closely resembles virtue theory. After a discussion of common features of Care
theories, I respond to a few of the criticisms that have been levied against the
theory. The final section of the paper is a discussion of the question of
neutrality in public moral discourse. Care theory is not a neutral theory with
regard to questions of the nature of the good life for humans, but I argue that
this should not preclude Care from playing a part in the public debate over
policy decisions.
PMID- 9638569
TI - Care: from theory to orientation and back.
AB - In this paper, I urge that the very real lessons Carol Gilligan's work in moral
psychology offer to moral philosophy can best be appreciated if we take seriously
the gap between the two disciplines. The care and justice perspectives Gilligan
explores are psychological orientations, and orientations are defined as much by
matters of emphasis, selectivity of interpretation, and gestalt as they are by
propositional commitment. As such, I argue, their contribution to moral theory is
best seen as stances from which to do theory, rather than as constituting ready
made theories themselves. In pursuing this train of thought, I examine how
Gilligan's work has developed over time and how, in the end, we should understand
the juxtaposition between the two orientations.
PMID- 9638570
TI - The place of care in ethical theory.
AB - The concept of care and a related ethical theory of care have emerged as
increasingly important in biomedical ethics. This essay outlines a series of
questions about the conceptualization of care and its place in ethical theory.
First, it considers the possibility that care should be conceptualized as an
alternative principle of right action; then as a virtue, a cluster of virtues, or
as a synonym for virtue theory. The implications for various interpretations of
the debate of the relation of care and justice are then explored, suggesting
three possible meanings for that contrast. Next, the possibility that care
theorists are taking up the debate over the relation between principles and cases
is considered. Finally, it is suggested that care theorists may be pressing for
consideration of an entirely new question in moral theory: the assessment of the
normative appropriateness of relationships. Issues needing to be addressed in an
ethic of relationships are suggested.
PMID- 9638571
TI - Advances in biopharmaceutical analysis in the People's Republic of China 1995
1997.
AB - The present paper is the third biannual review in succession to the author's
previous publications (Z.L. Qin, Advances in biopharmaceutical analysis in the
People's Republic of China: 1991-1993, J. Pharm. Biomed Anal. 13, 1995, 1-7 and
Z.L. Qin, Advances in biopharmaceutical analysis in the People's Republic of
China: 1993-1995, J. Pharm. Biomed. Anal. 14, 1996, 1395-1403), regarding the
methodological study and progress in biopharmaceutical analysis by RP-HPLC, GC
and GC-MS selected from relative journals between April 1995 and March 1997 in
P.R. China. The published methods were widely adopted in pharmacokinetic and
metabolic studies. Investigation on drug metabolism were conducted more deeply,
both in vitro and in vivo, for searching the structure of metabolites and drug
metabolic pathways. The use of high performance CZE as a new trend for the
analysis of drugs and metabolites in biofluids was also reported.
PMID- 9638572
TI - Validation of bioanalytical chromatographic methods.
AB - A strategy is discussed for the validation of chromatographic methods that are
developed to quantify drugs in biological matrices. Both the validation
terminology and the hypothesis testing are briefly reviewed. The emphasis is on
the design of the experiments required to allow a reliable conclusion about
acceptance or rejection of the bioanalytical method. In particular, it is
explained how to evaluate the calibration line, devise experiments to estimate
precision and bias and how to determine the stability of the analyte between the
time of the sample collection and the analysis of the processed sample.
PMID- 9638573
TI - Moisture determination in hygroscopic drug substances by near infrared
spectroscopy.
AB - The moisture level in a hygroscopic drug substance was successfully determined by
near infrared spectroscopy using coulometric Karl Fischer titration as the
reference method. The importance of sample handling and proper application of the
reference technique are stressed for this difficult sample type. Samples were
prepared with moisture levels from 0.5 to 11.4% (w/w) and reflectance spectra
were collected over the spectral range 1100-2500 nm. Calibration models were
built using partial least squares (PLS) regression analysis. Optimum models were
found by choosing proper spectral ranges and number of PLS factors. The best
calibration models were built using first derivative spectra, a spectral range of
1850-1936 nm and 5 PLS factors. The corresponding standard error of prediction
was 0.11% (w/w) water.
PMID- 9638574
TI - Comparison of p-fluoroketorolac and [18O3]ketorolac for use as internal standards
for the determination of ketorolac by gas chromatography/mass spectrometry
(GC/MS).
AB - A chemical and a stable-isotope analog, p-fluoroketorolac and [18O3]ketorolac
respectively, were directly compared for applicability as internal standards for
the determination of ketorolac in plasma samples using gas chromatography/mass
spectrometry (GC/MS) with selective-ion-monitoring detection, following
derivatization to form the methyl esters. This comparison involved analyzing
ketorolac calibration standards and spiked plasma samples that contained both
internal standard candidates. The response for ketorolac and each internal
standard was monitored simultaneously and electronically integrated peak heights
were obtained. Thus, for each analysis performed, a response ratio was obtained
for each internal standard relative to an identical ketorolac response. Linearity
of response for ketorolac calibration standards and accuracy for spiked plasma
sample analysis were compared using each internal standard. The use of
[18O3]ketorolac as the internal standard provided superior accuracy data for the
analysis of ketorolac in plasma samples.
PMID- 9638575
TI - Spectrofluorometric determination of piroxicam.
AB - The spectrofluorometric determination of piroxicam [4-hydroxy-2-methyl-N-(2
pyridyl)-2II-1,2-benzothiazine-3-carboxam ide-1, 1-dioxide] in pharmaceutical
tablets is described. It involves excitation at 330 nm of an acid solution (HNO3
0.5 M) of the drug, and measurement of the fluorescence intensity at 440 nm. The
linear range is 0.01-1.25 micrograms ml-1.
PMID- 9638576
TI - Simultaneous determination of dextromethorphan HBr and bromhexine HCl in tablets
by first-derivative spectrophotometry.
AB - A rapid, simple and direct assay procedure based on first-derivative
spectrophotometry, using a zero-crossing and peak-to-base measurement at 234 and
324 nm, respectively, has been developed for the specific determination of
dextromethorphan HBr and bromhexine HCl in tablets. Calibration graphs were
linear with the correlation coefficients of 0.9999 for both analytes. The limit
of detections were 0.033 and 0.103 microgram ml-1 for dextromethorphan HBr and
bromhexine HCl, respectively. A HPLC method has been developed as the reference
method. The results obtained by the first-derivative spectrophotometry were in
good agreement with those found by the HPLC method.
PMID- 9638577
TI - Enzyme-linked immunosorbent assay for TA-2005-glucuronide in human plasma.
AB - A sensitive enzyme-linked immunosorbent assay (ELISA) for TA-2005-glucuronide, a
main metabolite of new adrenergic beta-receptor agonist TA-2005, has been
investigated without prior deconjugation. Coupling of the hapten with bovine
serum albumin (BSA) or beta-D-galactosidase was carried out by the N
hydroxysuccinimide ester method. An anti-TA-2005-glucuronide antiserum was
obtained from guinea pig immunized with the hapten-BSA conjugate. The ELISA was
based upon a competitive assay in which the separation of bound from free
fraction was performed by the double antibody technique using rabbit anti guinea
pig immunoglobulin antibody adsorbed to microtiter plates. A satisfactory
standard curve for the ELISA of TA-2005-glucuronide was observed in the range of
30 pg-3 ng ml-1 using 25 microliters of human plasma. Inter-day and intra-assay
variations were 7.0-17.5% and 1.0-11.7% respectively. The recoveries of TA-2005
glucuronide spiked to plasma samples were 95.5-120% (inter-assay) and 96.0-123.3%
(intra-assay). The cross-reactivities of the prepared antiserum with the related
compound of TA-2005-glucuronide were quite low though there was a considerable
cross-reaction with TA-2005. However, TA-2005-glucuronide could be easily
separated from TA-2005 by a simple pretreatment of the plasma sample with a C18
cartridge column. This method was applied to the determination of TA-2005
glucuronide in human plasma samples for the evaluation of the pharmacokinetics of
TA-2005. From the results, it was demonstrated that the ELISA developed was
useful for the determination of TA-2005-glucuronide in human plasma and that the
method was applicable to pharmacokinetic studies in humans.
PMID- 9638578
TI - Simultaneous determination of an active metabolite and open-ring metabolites by
high performance liquid chromatography and pharmacokinetic studies of a penem
antibiotic, FCE22891, in dogs.
AB - A sensitive high performance liquid chromatographic method for the simultaneous
determination of an active metabolite (FCE22101) and open-ring metabolites (P1,
P2) of a penem antibiotic, FCE22891, in dog plasma was developed. Plasma samples
were pretreated only by ultrafiltration for the determination of the metabolites.
The filtrates were directly analyzed by a reversed-phase high-performance liquid
chromatographic system using a two-sided bracketing injection technique. The
quantitation limits of FCE22101, P1 and P2 were 0.03, 0.1 and 0.15 microgram ml
1, respectively. Analysis of the spiked plasma samples demonstrated the good
accuracy and precision of the method. The proposed method was applied to the
pharmacokinetic studies of an active metabolite and open-ring metabolites after
oral administration of a penem antibiotic, FCE22891, in dogs. In addition, the
plasma levels of unchanged FCE22891 and the possible changes of formaldehyde and
acyl-L-carnitine levels in plasma, which will be generated from the ester group
of FCE22891, were also investigated.
PMID- 9638579
TI - Flow-injection spectrophotometric determination of diclofenac sodium in
pharmaceuticals and urine samples.
AB - A sensitive and fast flow-injection spectrophotometric method for the
determination of diclofenac sodium based on the formation of coloured compound
with Ce(IV)-3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in H2SO4
3 x 10(-2) M medium is proposed. Using the peak height as a quantitative
parameter diclofenac was determined at 580 nm over the range 0.20-8.0 micrograms
ml-1. The proposed method was successfully applied to the determination of
diclofenac in pharmaceuticals and urine samples.
PMID- 9638580
TI - Polarographic determination of some penicillins through nitrosation.
AB - Direct current and differential pulse polarography DPP were used for the
determination of three penicillins, namely, ampicillin, benzylpenicillin and
carbenicillin, in pure form and in their dosage forms. The method is based upon
treatment of penicillins with nitrous acid followed by polarographic measurement
of the produced derivatives polarographically. The nitroso derivatives formed
exhibited reduction waves over the whole pH range in Britton-Robinson buffers.
The waves were characterized as being diffusion-controlled and free from
adsorption phenomena. The current-concentration plots were rectilinear over the
concentration range 8-200 and 2-160 micrograms ml-1 for DCt and DPP,
respectively, for all the studied compounds. The proposed method was further
applied to determine penicillins in pharmaceutical preparations, and the results
obtained were in good agreement with those given by the companies.
PMID- 9638581
TI - Oxidation of recombinant methionyl human granulocyte colony stimulating factor.
AB - The oxidation of methionine residues in recombinant methionyl human granulocyte
colony stimulating factor with hydrogen peroxide has been investigated. Kinetic
data of the oxidation were obtained by using reversed phase-high performance
liquid chromatography. The stability-indicating capability of this system was
confirmed with micellar electrokinetic capillary chromatography. In the pH range
1.9-7.5, the kobs value for the oxidation process is constant. Above pH 7.5, kobs
tends to increase with increasing pH. In the pH range 1.9-11.8, four oxidation
products were detected in RP-HPLC. Mass spectrometric analysis revealed that one
mono-, one di- and two trioxidation products were formed. Using the cyanogen
bromide cleavage method the nature of the oxidation products was determined. The
mono-oxidation product is the protein with Met121 oxidized, while the dioxidation
product has oxidized Met121 and Met126 residues. The trioxidation products are
the proteins with Met121, Met126 and Met137 or Met0, Met121 and Met126 oxidized.
PMID- 9638582
TI - Determination of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of
doxifluridine, in body fluids by high performance liquid chromatography.
AB - A high performance liquid chromatography method for the determination of N3
methyl-5'-deoxy-5-fluorouridine, a possible metabolic product of the anticancer
pro-drug 5'-deoxy-5-fluorouridine, in human serum and urine is described. Sample
treatment involved addition of internal standard (5-bromouracil) and protein
precipitation with ammonium sulphate (serum samples) followed by liquid-liquid
extraction with ethyl acetate-isopropanol (90:10, v/v). The average recovery at
0.5 mg ml-1 level was (80 +/- 4%). A linear response extending over two decades
of concentration was observed. Detection limits of 50 and 100 ng ml-1 were
obtained in serum and urine, respectively.
PMID- 9638583
TI - Electrochemical reduction of metronidazole at activated glassy carbon electrode
and its determination in pharmaceutical dosage forms.
AB - A voltammetric method has been developed for the determination of metronidazole
in dosage forms. The method is based on the electrochemical reduction of the drug
at a glassy carbon electrode activated by applying a new pretreatment. The
influence of pH, concentration, scan rate and presence of organic solvent and
surfactant has been studied. The current is proportional to the concentration and
permits the drug to be determined in the concentration range 2 x 10(-6)-6 x 10(
4) M in Britton-Robinson buffer (pH 10). Furthermore, results obtained by the
proposed method have been compared with USP XXIII procedure which involves a HPLC
method.
PMID- 9638584
TI - A novel technique for visualizing the intracellular localization and distribution
of transported polyamines in cultured pulmonary artery smooth muscle cells.
AB - The use of a combination of monofluorescein adducts of spermidine (FL-SPD) and
spermine (FL-SPM) with confocal laser scanning microscopy (CLSM) provides a
useful means for monitoring the fate and time-dependent changes in the
distribution of transported polyamines within living cells. Polyamine-fluorescein
adducts were synthesized from fluorescein isothiocyanate and the appropriate
polyamine. Monofluorescein polyamine adducts (ratio 1:1) were isolated using thin
layer chromatography, and the structure and molecular weight of the
monofluorescein polyamine adducts were confirmed using NMR and mass spectroscopy,
respectively. The covalent linkage of the fluorescent adduct moiety to SPD and
SPM did not influence their rate of uptake by bovine pulmonary artery smooth
muscle cells (PASMC). Similar to 14C-SPD and 14C-SPM, the rate of uptake of 14C
FL-SPD and 14C-FL-SPM in PASMC was temperature-dependent. Treatment for 24 h with
difluoromethylornithine (DFMO), a selective blocker of the enzyme ornithine
decarboxylase and an inducer of the polyamine transport system, significantly
increased the cellular uptake of 14C-FL-SPD and 14C-FL-SPM compared to that of
control cells. When compared to control cells, treatment of PASMC with the
pyrrolizidine alkaloid monocrotaline for 24 h also significantly increased the
cellular uptake of 14C-FL-SPD and 14C-FL-SPM. On the other hand, 24 h treatment
of PASMC with a polymer of SPM, a selective blocker of the polyamine transport
system, or with free spermine, markedly reduced the cellular accumulation of 14C
FL-SPD and 14C-FL-SPM. After a 20-min treatment of PASMC with FL-SPD or FL-SPM,
CLSM revealed that adduct fluorescence was localized in the cytoplasm of living
cells. Treatment with DFMO increased the cytoplasmic accumulation of both FL-SPD
and FL-SPM. In addition, the fluorescence observed in the cytoplasm of chinese
hamster ovary cells (CHO) was significantly higher than that detected in the
cytoplasm of their polyamine transport deficient variants (CHOMGBG). The results
of this study provide the first evidence of the utility of a novel method for
visualizing the uptake, distribution, and cellular localization of transported
polyamines in viable cultured mammalian cells.
PMID- 9638585
TI - Determination of (S)(-)-cathinone by spectrophotometric detection.
AB - Previous studies on the Khat plant (Catha edulis, Celastraceae) illustrated the
importance of using freshly harvested young shoots and leaves such that
cathinone, the principle active component and Schedule I controlled drug
contained within the plant, could be suitably isolated and identified. The
purpose of this work was to develop a quantitative analytical technique for the
determination of cathinone. The proposed method is based on treating the
reductant cathinone with copper(II)-neocuproine reagent in sodium acetate
buffered medium followed by measuring the absorbance of the copper(I)-neocuproine
complex at 455 nm. The calibration plot is linear in the range 0.08-25 micrograms
ml-1 with a detection limit of 0.08 microgram ml-1. The precision of the method,
expressed as the relative standard deviation, is 1.35% for 10 micrograms ml-1
cathinone. Good recoveries have been obtained in applying the method to the
analysis of cathinone in Khat leaves.
PMID- 9638586
TI - Acidic hydrolysis of bromazepam studied by high performance liquid
chromatography. Isolation and identification of its degradation products.
AB - A kinetic study on the acidic hydrolysis of bromazepam was carried out in 0.01 M
hydrochloric acid solution at 25 and 95 degrees C. A reversed-phase HPLC method
was developed and validated for the determination of bromazepam and its
degradation products. Bromazepam degraded by a consecutive reaction with a
reversible first step. Two degradation products were isolated and identified by
infrared, 1H and 13C nuclear magnetic resonance and mass spectroscopy.
Spectroscopic data indicated that N-(4-bromo-2-(2-pyridylcarbonyl)phenyl)-2
aminoacetamide was the intermediate degradation product of this acid hydrolysis,
whereas 2-amino-5-bromophenyl-2-pyridylmethanone was the final one. Therefore,
the mechanism of this acid-catalysed hydrolysis involved initial cleavage of the
4,5-azomethine bond, followed by slow breakage of the 1,2-amide bond. Statistical
evaluation of the HPLC method revealed its good linearity and reproducibility.
Detection limits were 3.8 x 10(-7) M for bromazepam, 6.25 x 10(-7) M for the
intermediate and 8.16 x 10(-7) M for the benzophenone derivative.
PMID- 9638587
TI - HPLC analysis of pharmaceutical estrogens in raw materials and dosage forms.
AB - The use of HPLC with fluorescence detection (lambda ex = 280 nm; lambda em = 410
or 312 nm) in combination with a postcolumn on line photochemical derivatization
was investigated for the analysis of conjugated and unconjugated estrogens and
their correlated impurities. The column effluents were subjected on-line to UV
irradiation (254 nm) and the photo induced modifications were useful for the
identification of the various estrogens. The proposed HPLC methods were
successfully applied to the analysis of commercially available conjugated
estrogens (raw materials and pharmaceuticals) and estrogen samples. The assays
results relative to the pharmaceutical formulations were in agreement with those
obtained by a reference HPLC method with UV detection (lambda = 280 nm).
PMID- 9638588
TI - Determination of terbutaline based on oxidation by voltammetry.
AB - A voltammetric study of the oxidation of terbutaline has been carried out at an
activated glassy carbon electrode. The compound was oxidized irreversibly at high
positive potential. The response was evaluated with respect to pH, scan rate,
nature of the buffer and other variables. The peak current, at about 0.8 V
(versus a saturated calomel electrode), was proportional to the terbutaline
concentration in the range of 8 x 10(-6)-8 x 10(-4) M in phosphate buffer pH 6.0.
This method was applied, without any interferences from the excipients, to
determine the drug in a tablet dosage form.
PMID- 9638589
TI - Field method for the micro-quantitative determination of tetracycline in human
blood serum.
PMID- 9638590
TI - Effect of .OH scavenging action by non-SH-containing angiotensin converting
enzyme inhibitor imidaprilat using microdialysis.
AB - We examined the effect of non-SH-containing angiotensin converting enzyme (ACE)
inhibitor imidaprilat on hydroxyl radical (.OH) generation using microdialysis.
Salicylic acid in Ringer's solution containing sodium salicylate (0.5 n mol
microL-1 min-1) was infused directly through a microdialysis probe to detect the
generation of .OH as reflected by the formation of 2,3-dihydroxybenzoic acid
(DHBA) in the myocardium of anesthetized rats. We compared the ability of two non
SH-containing ACE inhibitors (imidaprilat and enalaprilat) with an -SH-containing
ACE inhibitor (captopril) to scavenge the .OH. When iron (II) was administered to
animals pretreated with these three ACE inhibitors, a decrease in 2,3-DHBA of all
three compounds was observed, as compared with the iron (II) only-treated group.
All three ACE inhibitors were able to scavenge .OH generated by the action of
iron (II). However, imidaprilat is a free radical scavenger more potent than
enalaprilat. These results suggested that ACE inhibitors are probably not only
related to the presence of the SH radical.
PMID- 9638591
TI - Involvement of AMPA receptors in posterior locomotor activity in the rabbit: an
in vivo study.
AB - Although AMPA receptors are known to be widely involved in excitatory synaptic
neurotransmission at the spinal level, very little is known about their role in
modulating motor activity in mammals. In curarized decerebrate or spinalized
rabbit preparations, fictive locomotion was monitored on hindlimb nerves after
either activation or blockade of AMPA receptors. In decerebrate preparations, the
administration of the antagonist, NBQX (3.5 mg/kg i.p.) or the agonist, AMPA (0.5
mg/kg i.v.) produced, in both cases, a depression of locomotor activities induced
by stimulation of cutaneous afferents (evoked locomotor activity). This potent
effect was transient with AMPA (recovery after 20 min) and followed by the
occurrence of spontaneous locomotor sequences, while no recovery was observed
with NBQX treatment. In spinal preparations where a continuous 'spontaneous'
locomotor activity resulted from the pharmacological activation of noradrenergic
descending pathways (nialamide-DOPA pretreatment), the same drugs injected at
higher doses (5 mg/kg NBQX i.p. and 1 mg/kg AMPA i.v.) only weakly affected the
frequency of 'spontaneous' and evoked locomotor bursts while they exerted
inhibitory and facilitatory effects on the burst amplitude respectively. The
results suggest that AMPA receptors are involved at spinal level: 1) in direct
mediation of cutaneous afferent excitatory effects on the posterior locomotor
generators (pLG); 2) in indirect mediation of a supraspinal descending inhibition
controlling, likely presynaptically, the cutaneous afferent activation; and 3) in
transmission to motoneurons of the output signals from the pLG. Finally, tight
spinal interactions between potent descending noradrenergic pathways and spinal
AMPA neurotransmission were disclosed.
PMID- 9638592
TI - Opioid peptide involvement in the bulbar inhibition of electrodermal activity in
the cat.
AB - By analogy with supraspinal and spinal inhibitory controls of pain, it was
hypothesized that an opioid mechanism could be involved in the bulbar inhibitory
control of the electrodermal activity. This activity was evoked as skin potential
responses on the footpads of 13 cats by the central tegmental field stimulation
(control responses) and inhibited by the simultaneous stimulation of bulbar
reticular formation (experimental responses). Then, naloxone, an opioid peptide
antagonist, was injected intravenously or intrathecally and its effects were
analyzed on both control and experimental responses. Intravenous injections of
naloxone increased significantly the amplitude of experimental responses from 6
to 12 min after the injection and had no effect on the amplitude of control
responses. Intrathecal injections of naloxone induced significant increases of
amplitude of experimental responses from 6 to 42 min after the injection. These
results showed that a spinal opioid peptide link could be involved in bulbar
inhibition mechanisms of electrodermal activity.
PMID- 9638593
TI - Imidazoline receptors of the paraventricular nucleus on the pressor response
induced by stimulation of the subfornical organ.
AB - In the present experiments we investigated a possible involvement of imidazoline
receptors of the paraventricular nucleus (PVN) of the hypothalamus on the pressor
effects of the angiotensin II (ANG II) injected into the subfornical organ (SFO),
in male Holtzman rats (250-300 g) with a cannula implanted into the third
ventricle (3rdV), PVN and SFO. At first we tested the participation of alpha 2
and imidazoline agonist and antagonist compounds on the pressor effect of ANG II
injected into the 3rdV. Based on the results we may conclude that clonidine
associated with rilmenidine was able to block the hypertensive response to ANG
II. The ANG II (20 pmol) injected into SFO induced a robust increase in blood
pressure (37 +/- 2 mmHg). Isotonic saline (0.15 M) NaCl did not produce any
change in blood pressure (5 +/- 2 mmHg). The injection of rilmenidine (30
micrograms/kg/1 microL), an imidazoline agonist agent injected into PVN before
ANG II injection into SFO, blocked the pressor effect of ANG II (5 +/- 2 mmHg).
Also, the injection of idazoxan (60 micrograms/kg/microL) before rilmenidine
blocked the inhibitory effect of rilmenidine on blood pressure (39 +/- 4 mmHg).
The injection of clonidine (20 nmol/microL) prior to ANG II into the 3rdV
produced a decreased in arterial blood pressure (37 +/- 2 mmHg) to (15 +/- 4
mmHg). The injection of yohimbine (80 nmol/microL) prior to clonidine blocked the
effect of clonidine on the effect of ANG II (27 +/- 2 mmHg). The injection of
rilmenidine prior to ANG II also induced a decrease in arterial blood pressure
(10 +/- 3 mmHg). The injection of idazoxan prior to rilmenidine also blocked the
inhibitory effect of rilmenidine (24 +/- 3 mmHg). In summary, the present study
demonstrated that rilmenidine decreases the hypertensive effect of ANG II, with
more potency than clonidine, even when injected into 3rdV or PVN. This study
established that the PVN interacts with SFO by imidazoline receptors in order to
control the arterial blood pressure.
PMID- 9638594
TI - Glucose-induced mobilisation of intracellular Ca2+ in depolarised pancreatic
islets.
AB - Perifused rat pancreatic islets, prelabelled with 45Ca, were exposed for 90 min
to a medium containing 30 mM K+, 0.25 mM diazoxide and 0.5 mM EGTA, but deprived
of CaCl2. Either verapamil (0.05 mM) or Cd2+ (0.05 mM) were also present in the
perifusate. Under these conditions a rise in D-glucose concentrations from either
2.8 to 16.7 mM or zero to 8.3 mM increased both 45Ca outflow and insulin release,
after an initial and transient decrease in effluent radioactivity. These findings
suggest that, in islets depolarised by exposure to a high extracellular
concentration of K+, D-glucose provokes an intracellular redistribution of Ca2+
ions and subsequent stimulation of insulin release. The functional response to D
glucose is apparently not attributable to either the closing of ATP-sensitive K+
channels, which were actually activated by diazoxide, or stimulation of Ca2+
influx, which was prevented by the absence of extracellular Ca2+. The present
experimental design thus reveals a novel component of the glucose-induced
remodelling of Ca2+ fluxes in islet cells. Such an effect might also be operative
under physiological conditions, when the hexose leads to depolarisation of the
islet B-cells.
PMID- 9638595
TI - Lumbar collaterals of neurons of the C6 segment projecting to sacral segments of
the cat spinal cord.
AB - Electrophysiological investigations of neurons of the C6 segment of the spinal
cord were made in alpha-chloralose anesthetized animals. It was established in
the experiments that a part of long descending propriospinal neurons originating
in the sixth cervical segment (C6) that projected to sacral segments (S1/S2) gave
off collateral branches at the level of the fourth lumbar segment (L4). Several
types of neurons were distinguished according to the ipsilateral, contralateral
or bilateral course of axons at the thoracic level as well as their lumbar or
sacral projections. The cell bodies of 58 identified neurons were distributed in
Rexed's laminae VII and VIII of the gray matter. Axons descended in lateral
funiculi and their conduction velocities varied from 50 to 85 m/s. The existence
of collaterals to various segments of the lumbosacral enlargement indicates that
the same information conveyed by long descending propriospinal neurons can reach
separate motor centers controlling various muscles of the hindlimbs.
PMID- 9638596
TI - Characteristic frequency bands of the cortico-frontal EEG during the sexual
interaction of the male rat as a result of factorial analysis.
AB - The electrocorticogram (ECoG) from the prefrontal cortex was simultaneously
recorded with the accelerometric signals of pelvic thrusting performed by male
rats during sexual behavior. The changes in the prefrontal ECoG were precisely
correlated in time with well defined elements of male rat copulation. Principal
component analysis allowed to identify three distinct bands of frequencies in the
frontal ECoG: the absolute power (AP) of the 4-16 Hz band was increased in the
500-ms periods before, during, and after the execution of pelvic thrusting in
mount, intromission and ejaculation responses; the AP of the 18-24 Hz band was
selectively increased during the execution of pelvic thrusting at the three
copulatory responses, whereas the AP of the 26-32 Hz band was increased only
during the pelvic moments of mount and intromission responses. These results show
that the electroencephalographic activity of the prefrontal cortex of the male
rat is related to the performance of sexual behavior, supporting the concept that
this cortical area is involved in the organization of sequential behaviors, as
sexual behavior.
PMID- 9638597
TI - Deiodinase activity after short cold stimulation in rat.
PMID- 9638598
TI - The free woman.
PMID- 9638599
TI - Psychosomatic obstetrics and gynecology in the next millennium: some thoughts and
observations.
AB - While the importance of psychosocial and cultural issues inobstetric care has
been increasingly acknowledged in recent decades there is still neglect and
misunderstanding of what women want during pregnancy, birth and the postpartum
period with regard to their care by health care providers. This paper highlights
significant issues of concern which should be of value for caregivers, educators
and health service planners as we move into the next millenium.
PMID- 9638600
TI - A follow-up study of adolescent girls with early sexual debut in combination with
gynecological problems.
AB - This research examined the extent to which women's reproductive experiences
during adolescence have repercussions in adult life with regard to sexuality,
self-image and state of gynecological health. The investigated group comprised 30
females (study group), with a sexual debut at the age of 15 years or younger and
documented gynecological ill-health during adolescence. A comparison was made
with 30 matched females from the same school classes (control group) without
documented gynecological ill-health. At the age of 25-30 a semi-structured
interview was conducted with both investigated and control participants. The
majority of the women from the study group experienced their adolescent sexual
experiences as generally negative. In early adulthood these women had more
recurrent and varied gynecological illnesses than their control group
counterparts. The study group women more often referred to their appearance as an
indicator of their femininity than did the control women (who defined femininity
in terms of 'to be in a relationship'). The study group women had a more negative
attitude towards their own body than did the control women. Study group women's
early sexual experience was also linked to an increase in norm-breaking behavior,
lower educational attainment and a younger age of adult responsibilities compared
with the control women.
PMID- 9638601
TI - Psychometric aspects of the W-DEQ; a new questionnaire for the measurement of
fear of childbirth.
AB - Up to now it has been difficult to study fear of childbirth because of a shortage
of adequate psychological measurements. Therefore the Wijma Delivery Expectancy/
Experience Questionnaire (W-DEQ) was developed. This paper presents the
theoretical background of the W-DEQ together with a documentation of the first
psychometric studies. Examination of construct validity indicates that it seems
to be possible to penetrate a psychological construct related to fear of
childbirth by means of the W-DEQ, both before and after delivery, in nulliparous
as well as in parous women. The questionnaire measures the construct more clearly
in parous than in nulliparous women. Internal consistency reliability and split
half reliability of the W-DEQ of > or = 0.87 are good for a new research
instrument. More research is on its way to make the W-DEQ suitable even for
measurements in applied settings.
PMID- 9638602
TI - A comparative study of vertical and horizontal deliveries in the presence and
with the assistance of the woman's partner.
AB - The authors are the first in Hungary to have applied the method of vertical
delivery with the husband's or partner's presence in the delivery room. This is
part of the authors' family-centered delivery program at the Maternity Ward of
Borsod-Abauj-Zemplen County Hospital, Miskolc. A comparison of 321 births was
carried out, which included 158 vertical deliveries and 163 horizontal
deliveries. During both vertical and horizontal deliveries, the husband or
partner was present in the delivery room. The comparison included the mother's
biometrics and social characteristics, as well as the circumstances of the
delivery and the clinical parameters of the newborns. Certain stages of delivery
in the vertical position took a shorter period of time compared to horizontal
delivery, but the differences were not significant. Episiotomies were carried out
in fewer cases of vertical deliveries, and significant injuries due to the lack
of an episiotomy in the case of vertical deliveries were not detected. The
parameters characterizing the clinical state of the newborns were the same in
both groups. The answers given to questionnaires supported the favorable
psychological effects of a vertical delivery. The authors hope that vertical
delivery, as a possible alternative, will find its place in obstetric practice in
Hungary.
PMID- 9638603
TI - Puerperal and menstrual psychoses: the proposal of a unitary etiological
hypothesis.
AB - Puerperal and menstrual psychoses are both uncommon disorders and the occurrence
of both in individual patients suggests the possibility of a common underlying
pathogenesis. In this paper two cases are reported, the literature is reviewed
and a unifying etiological hypothesis is postulated in which precipitous
reductions in the brain estrogen environment precipitate episodes of psychosis in
predisposed individuals. In the case of puerperal psychosis, estrogen cascade
follows a lengthy period of sustained high brain estrogen environment; in
menstrual psychosis, it is postulated that the occurrence in at least some cases
of anovulatory menstrual cycles, wherein high levels of relatively unopposed
estrogens are maintained until the next ovulatory cycle, play a role in priming
the central nervous system prior to premenstrual estrogen cascade. Further
research in this area using more sensitive techniques to follow hormonal
fluctuation and mental state is called for.
PMID- 9638604
TI - Assessment of menstrual regularity and irregularity using self-reports and
objective criteria.
AB - To assess subjective and objective definitions of menstrual regularity, and the
relationship between them, 114 university students (mean age 20.3 years)
prospectively recorded eight consecutive menstrual dates and reported whether
they considered themselves 'regular' or 'irregular'. The percentage of women who
reported being menstrually 'regular' or menstrually 'irregular' was compared with
a classification developed according to a criterion based upon the results of
their prospective menstrual records. According to self-reports and objective
measures of regularity, a similar portion of the women (about 70%) were regular.
But when cross-classifying regularity and non-regularity by the two procedures,
it was found that only 44% of those who defined themselves as irregular were
likewise defined by the objective criteria, whereas 82% of the women who defined
themselves as regular were also deemed so by the objective criteria. It is
concluded that some women will, and others will not, construe 'variability' as
'irregularity'.
PMID- 9638605
TI - Measured copper and zinc in body fluids.
PMID- 9638606
TI - In vivo and in vitro effects of boron and boronated compounds.
AB - Boron is ubiquitously present in soils and water. Associated with pectin it is
essential for vascular plants as a component of cell walls, and it stabilizes
cell membranes. It is required for the growth of pollen tubes and is involved in
membrane transport, stimulating H(+)-pumping ATPase activity and K+ uptake.
However, a high boron concentration in the soils is toxic to plants and some
boronated derivatives are used as herbicides. An absolute requirement for boron
has not been definitively demonstrated in animals and humans. However,
experiments with boron supplementation or deprivation show that boron is involved
in calcium and bone metabolism, and its effects are more marked when other
nutrients (cholecalciferol, magnesium) are deficient. Boron supplementation
increases the serum concentration of 17 beta-estradiol and testosterone but boron
excess has toxic effects on reproductive function. Boron may be involved in
cerebral function via its effects on the transport across membranes. It affects
the synthesis of the extracellular matrix and is beneficial in wound healing.
Usual dietary boron consumption in humans is 1-2 mg/day for adults. As boron has
been shown to have biological activity, research into the chemistry of boronated
compounds has increased. Boronated compounds have been shown to be potent anti
osteoporotic, anti-inflammatory, hypolipemic, anti-coagulant and anti-neoplastic
agents both in vitro and in vivo in animals.
PMID- 9638607
TI - Distribution of selenium between plasma fractions in guinea pigs and humans with
various intakes of dietary selenium.
AB - The distribution of selenium between the plasma fractions was investigated in
guinea pigs fed various levels (basal, 0.5, 1.0, 2.0, 4.0, 6.0 and 8.0 mg Se/kg)
of dietary selenomethionine (Semet) and in humans living in different areas of
China with different selenium status. There was a corresponding increase of
selenium concentration in liver, kidney, brain, testis, spleen, heart and muscle
with each increase of dietary selenium, but there were no increases of
glutathione peroxidase (GPX) activity in liver, brain, testis, heart or muscle in
pigs fed any of the selenium levels as compared to controls fed a basal
commercial diet. On a percentage distribution basis, the selenium in
selenoprotein P decreased and that in the albumin fraction increased with
increased dietary intakes of selenium as Semet. The ratios of selenium to albumin
in either the plasma or the albumin fractions increased with each increase in
dietary selenium. The greatest percentage of selenium was in the albumin fraction
of Chinese living in the high selenium areas whereas the greatest amount was in
the selenoprotein P fraction in subjects living in deficient and adequate areas
of China. Increases in the ratios of selenium to albumin in either the plasma or
the albumin fraction also occurred with increases of selenium intake of these
subjects. The results indicate that the distribution of selenium in plasma
fractions reflect the levels of dietary intakes of Semet.
PMID- 9638608
TI - An in vivo study of the gastrointestinal absorption site for zinc chloride in
mice.
AB - The experimental model presented below enables quantitation of the uptake of zinc
(Zn++) into gastrointestinal mucosal cells in vivo using gamma-counting of 65Zn.
Experiments were performed in mice fed their normal diet under natural
physiological conditions. The in vivo site(s) of significant zinc absorption may
thereby be identified. Absorption of zinc was extensive during the first hour
after administration of a single oral dose of ZnCl2. Apparently, absorption
continued during at least eight hours postdosage, and probably continued for 48
hours. The intestinal mucosal labelling profile for zinc did not depend on dose
size or the mode of administration (single oral doses or in drinking water). The
duodenum and ileum were important sites for rapid zinc absorption. A continuous,
slower absorption of zinc may take place in the jejunum. The stomach, caecum and
colon appeared to be insignificant sites of zinc absorption. The transit time for
zinc was very short as large quantities of zinc passed through the small
intestine within one hour. In contrast to other studies, the intestinal labelling
profile or the extent of zinc absorption were not changed in mice that received
Tetraethylthiuram disulfide (TTD) in their food.
PMID- 9638609
TI - Mercury in human colostrum and early breast milk. Its dependence on dental
amalgam and other factors.
AB - The mercury concentration in 70 breast milk samples (Hg-M) from 46 mothers,
collected within the first 7 days after delivery, was determined by cold vapour
atomic absorption spectrometry. For comparison, 9 formula milk samples
(reconstituted with Hg-free water) were investigated. The Hg-M in the human milk
samples ranged from < 0.2 to 6.86 micrograms/L (median 0.37), in the formula milk
samples from 0.4 to 2.5 micrograms/L (median 0.76). The Hg-M in the breast milk
samples correlates positively with the number of maternal teeth with dental
amalgam. The mean Hg-M of amalgam-free mothers was < 0.2 microgram/L, while milk
from mothers with 1-4 amalgam fillings contained 0.57 microgram/L, with 5-7
fillings 0.50 microgram/L and with more than 7 fillings 2.11 micrograms/L. Hg-M
correlated negatively to the day after delivery. Frequency of fish consumption
tends to influence Hg-M positively, while the age of the mother shows no
significant correlation. In the first 2 to 3 days after delivery some colostrum
samples with Hg-M higher than in formula milk were found. Later on, the Hg
concentration in the breast milk was equal or even lower to that in formula milk.
The higher Hg burden of infants' tissues from mothers with dental amalgam, as
reported previously, must be explained (1) by a prenatal transfer of Hg from the
mother's fillings through the placenta to the fetus, followed by a redistribution
of this Hg in the body of the newborn, and (2) an additional burden via breast
milk. Nevertheless, the comparison of Hg-M in breast and formula milk, the
relatively moderate Hg burden in both kinds of milk, and the multiple manifest
advantages of breast feeding speak against any limitation of nursing, even for
mothers with a large number of dental amalgam fillings.
PMID- 9638610
TI - Trace elements and cardioprotection: increasing endogenous glutathione peroxidase
activity by oral selenium supplementation in rats limits reperfusion-induced
arrhythmias.
AB - Oxyradicals have been implicated as a possible cause of reperfusion-arrhythmias
(RA). However, the use of diverse exogenous oxyradical scavengers designed to
reduce RA has given contradictory results. The aim of the present study was to
determine whether enhancing the activity of the main endogenous enzyme involved
in peroxide elimination in cardiac cells, namely glutathione peroxidase, may
limit RA in isolated heart preparations by increasing their antioxidant status.
For this purpose, a group of 15 male Wistar rats received a selenium enriched
diet for ten weeks (1.5 mg Se/kg diet). Control animals (n = 15) received a
standard diet containing 0.05 mg Se/kg diet. The incidence of early ventricular
arrhythmias was investigated during the reperfusion period following 10 min
regional ischemia induced ex-vivo by left coronary artery ligation. Our results
show that selenium-supplementation significantly increased the global selenium
status of the animals. In the isolated heart preparations, the selenium
supplementation induced a significant reduction of the severity of RA as assessed
by the arrhythmia score and the limitation of the incidence of both ventricular
tachycardia (control: 91% vs selenium: 36%, p < 0.05) and irreversible
ventricular fibrillation (control: 45% vs selenium: 0%, p < 0.05). These effects
were associated with a significant increase in cardiac mitochondrial and
cytosolic glutathione peroxidase activities in both the left and the right
ventricles. These results illustrate the potential protective effect of selenium
against ischemia-reperfusion injury and suggest that peroxides might play a key
role in the genesis of some aspects of the reperfusion syndrome.
PMID- 9638611
TI - Serum glycerol ester hydrolase activity is related to zinc and copper
concentrations in atherosclerosis obliterans and aneurysm.
AB - Although the body status of zinc and copper in cardiovascular disease (CVD) has
been shown to be important little is known about the effect of these trace
element alterations on lipolytic enzyme activities in atherosclerosis human
subjects. The aim of the present study was to evaluate the multiple relationships
between lipase (GEH = glycerol ester hydrolase, EC 3.1.1.3) activity, zinc,
copper and lipid concentrations in serum and the arterial wall of men with
atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). The mean
concentrations of zinc and copper in serum were found to be higher in AO in
comparison to AA. Low but significant correlation coefficients for zinc and
lipase catalytic activity (r > or = 0.64) and lipase metabolic activity GEH/TAG
(r > or = 0.67) were calculated in serum in AA. Multiple correlation coefficients
(R) for three variables GEH-Zn-Cu were found to be significant for both AO and AA
(R > or = 0.45 and 0.68, respectively) in serum but not in the arterial wall.
Multiple relations for GEH/TAG-HDL-C (LDLC)-Zn(Cu) were found to be significant
(R > or = 0.63) in serum in AA. The results indicate the influence of zinc and
copper on the activity of lipase and lipid concentrations and suggest that the
multiple relations may provide a better understanding of the role these elements
play in atherosclerosis than relations between 2 substances.
PMID- 9638612
TI - Serum zinc and copper concentrations and Cu/Zn ratios in patients with
hepatopathies or diabetes.
AB - The serum zinc and copper levels, as well as Zn/Cu ratios, were determined in 30
patients (18 with diabetes and 12 with hepatopathies) and compared to healthy-age
matched controls by atomic absorption spectrometry. Serum Zn (0.946 +/- 0.302
mg/l) and Cu (0.952 +/- 0.355 mg/l) concentrations were not significantly
different in patients with hepatopathies as compared to controls (p > 0.05).
Serum Zn concentrations (0.778 +/- 0.164 mg/l) were significantly lower in
diabetic patients than those determined in controls (p < 0.01). In contrast, Cu
levels (0.987 +/- 0.305 mg/l) were not significantly different (p > 0.05) than in
controls. Serum Cu/Zn ratios were not significantly different in patients with
diabetes or hepatopathies than those measured in healthy controls (p > 0.05). In
patients, no statistically significant differences were observed in the Zn, Cu
and Cu/Zn with respect to sex (p > 0.05) or age (p > 0.05).
PMID- 9638613
TI - Adsorptive stripping measurements of iron accumulation in mice kidney using
microelectrodes and histological features.
AB - The toxic effects caused by iron in kidney was performed on experimental studies
with mice following administration of a metallic solution of this species to
simulate the iron corrosion products of a metallic implant. To quantify the total
levels of iron present in this organ, an electrochemical method was chosen based
on the application of square wave voltammetry using adsorptive collection of iron
catechol on a mercury film microelectrode (MFM). The optimal working conditions
to produce a very stable and reproducible iron peak in the digested kidney
samples were found to be pH = 7.2 provided by 8.0 mmol/L PIPES buffer, catechol
concentration of 3.0 x 10(-4) mol/L, deposition potential -1.80 V and deposition
time 20 s. These results were compared with those obtained by atomic absorption
spectrometry (AAS) indicating a good performance of the electrochemical method
used. The analytical results show an increase of iron concentration with
treatment time, which indicates that this metal ion is partially accumulated in
the kidney. This accumulation induces with time some morphological alterations as
evidenced by the histological analysis.
PMID- 9638614
TI - On the interaction of the VO2+ cation with cystine.
AB - The interaction between the VO2+ cation and cystine was investigated by electron
absorption spectroscopy in aqueous solutions at different metal-to-ligand ratios.
Reduction of NaVO3 solutions with cysteine gave similar spectra. The results
suggest that interaction occurs through the carboxylate and amino groups of the
ligand. The interest of the results in relation to vanadium metabolism are
commented upon.
PMID- 9638615
TI - Review of publications.
PMID- 9638616
TI - The effects of melengestrol acetate on the ovaries of captive wild felids.
AB - Melengestrol acetate (MGA) is the most widely used contraceptive in zoo felids,
but the mechanism of contraception and the pathologic effects have not been
investigated. For this study, the effects of MGA on folliculogenesis were
assessed, and the association of MGA with ovarian lesions was evaluated.
Comparisons were made among the histopathologic findings in the ovaries from 88
captive wild felids (representing 15 species) divided into three groups: 37
currently contracepted with MGA, eight previously exposed to MGA, and 43 never
contracepted. Ninety-one percent of the felids evaluated had tertiary follicles,
and no differences were noted between contracepted and uncontracepted cats. Some
MGA-contracepted cats also had corpora lutea indicating recent ovulation. These
results indicate that folliculogenesis not suppressed by current doses of MGA and
ovulation occurred in some cats. Therefore, the contraceptive actions of MGA do
not occur by suppressing folliculogenesis, and MGA-contracepted felids likely
have endogenous estrogens that may confound progestin effects on the uterus.
Cystic rete ovarii was the most common pathologic finding, but they were not more
prevalent in MGA-contracepted cats. These findings indicate that MGA is not
associated with ovarian disease, including ovarian cancer, in contrast to the
uterine lesions noted in MGA-treated cats.
PMID- 9638617
TI - Ultrasonographic evaluation of the effects of exogenous gonadotropins on
follicular recruitment and ovulation induction in the Atlantic bottlenose dolphin
(Tursiops truncatus).
AB - Transabdominal ultrasonography and serum steroid concentrations were used to
evaluate the effects of exogenous gonadotropin administration on ovarian activity
of two anestrous bottlenose dolphins (Tursiops truncatus). The gonadotropin used
for follicular recruitment was PG600, which has 400 IU equine chorionic
gonadotropin (eCG) and 200 IU human chorionic gonadotropin (hCG) activity per 5
ml. Ovulation induction was attempted with hCG. PG600 was administered in two
doses of 20 ml (1,600 IU eCG and 800 IU hCG) and 12.5 ml (1,000 IU eCG and 500 IU
hCG), respectively, 48 hr apart on days 0 and 2. On day 6, 1,500 IU of hCG was
administered. Progesterone and total immunoreactive estrogens were determined
before and after the gonadotropin administration. Bilateral ovarian
ultrasonographic exams were performed daily on days 4-9 and on day 22. Serum
immunoreactive estrogen concentrations were greater than the pretreatment
concentrations after day 4 for both dolphins and remained elevated for the rest
of the study. Serum progesterone concentrations rose above 1 ng/ml 2 days after
hCG treatment and remained elevated for the rest of the study. Small antral
follicles (< 0.5 cm) were initially observed bilaterally in both dolphins on day
4. In both animals on day 9, there were > 12 follicles/ovary, ranging from 0.5 to
1.5 cm. By day 22, the multiple follicles ranged from 0.5 to 4.5 cm in diameter.
No ultrasonographic evidence of luteal formation was observed. The results
indicate that 1) transabdominal ultrasonography can be used to detect and follow
follicle growth in bottlenose dolphins; 2) bottlenose dolphins are sensitive to
exogenous gonadotropins (multiple follicular recruitment of follicles occurred);
and 3) until further ultrasonographic studies can be conducted to evaluate the
effects of titrated doses of exogenous gonadotropins, these protocols should be
considered unsuitable for ovulation induction.
PMID- 9638618
TI - The effects of short-term physical restraint and isoflurane anesthesia on
hematology and plasma biochemistry in the island flying fox (Pteropus
hypomelanus).
AB - The effects of short-term physical restraint and isoflurane anesthesia on
hematologic and serum biochemistry parameters were evaluated in 12 island flying
foxes (Pteropus hypomelanus). Physical restraint was associated with
significantly decreased calcium, cholesterol, globulin, albumin, hemoglobin
concentrations, red blood cell count, and hematocrit and increased glucose,
phosphorus, and potassium concentrations. Isoflurane restraint was associated
with significantly decreased calcium, cholesterol, albumin, globulin, and glucose
concentrations, aspartate transaminase and alkaline phosphatase activities, white
blood cell count, red blood cell count, hemoglobin, hematocrit, and total
neutrophil and lymphocyte counts and significantly increased phosphorus and
chloride concentrations. For those variables where both restraint forms produced
an alteration (red blood cell count, hemoglobin, hematocrit, calcium, phosphorus,
glucose), the magnitude of change was always significantly greater for the
physically restrained animals. This study indicates that in adult flying foxes
isoflurane anesthesia is preferable to physical restraint for collection of blood
samples for hematologic and plasma biochemical analysis. Additionally, blood
samples should be collected as soon as possible after capture, regardless of
restraint technique.
PMID- 9638619
TI - Serologic survey of free-living nestling prairie falcons (Falco mexicanus) for
selected pathogens.
AB - Serum samples from 34 free-living nestling prairie falcons (Falco mexicanus) in
southwestern Idaho were negative for antibodies to avian influenza virus,
Newcastle disease virus, and three Aspergillus species. Serum from a single bird
had hemagglutinating inhibition activity in response to Mycoplasma synoviae, and
another bird's serum had slight activity in response to M. gallisepticum.
PMID- 9638620
TI - Use of monoclonal antibodies against chicken coccidia to study invasion and early
development of Eimeria gruis in the Florida sandhill crane (Grus canadensis).
AB - Eimeria gruis and E. reichenowi are common coccidial parasites of a number of
crane species. In the present study, monoclonal antibodies (McAbs), elicited
against Eimeria spp. of chickens and turkeys, cross-reacted with sporozoites and
developmental stages of E. gruis in the tissues of Florida sandhill cranes. These
McAbs were used to define the area of the intestine that was invaded by
sporozoites of E. gruis and to demonstrate the feasibility of using McAbs to
study the early development of E. gruis in the intestines and visceral organs of
cranes. At 6 hr postinoculation (PI), E. gruis sporozoites were found primarily
from just proximal to Meckle's diverticulum in the jejunum to the ileocecal
juncture. Fewer sporozoites were found in the ceca and rectum, and none were
found in the duodenum. Most of the sporozoites were in the middle third of the
villi and within the lamina propria. At 14 days PI, developmental stages were
detected in the ceca, jejunum, liver, and lungs but not in the heart, kidney, or
brain. In the ceca and jejunum, the number, location, and maturity of the stages
differed markedly.
PMID- 9638621
TI - Trypanosoma cruzi infection of free-ranging lion-tailed macaques (Macaca silenus)
and ring-tailed lemurs (Lemur catta) on St. Catherine's Island, Georgia, USA.
AB - Free-ranging Old World primates released on St. Catherine's Island, Georgia
(USA), were tested for infection with Trypanosoma cruzi as part of a study of the
epizootiology of sylvatic T. cruzi in the southeastern USA. The parasite was
observed in liver infusion tryptose medium cultures of blood from seven of 11
lion-tailed macaques (Macaca silenus) and one of 19 ring-tailed lemurs (Lemur
catta). Cultures of blood from 10 black and white ruffed lemurs (Varecia
variegata) were all negative. Analysis of small subunit ribosomal RNA gene
polymorphisms detected using polymerase chain reaction techniques indicates that
the parasites isolated from both the lion-tailed macaques and the ring-tailed
lemur are probably the same as T. cruzi parasites isolated from raccoons (Procyon
lotor) trapped on St. Catherine's Island and other locations in the southeastern
USA. Foraging lion-tailed macaques were observed to handle and partially consume
specimens of Triatoma sanguisuga, the triatomine bug thought to be a vector of T.
cruzi in the southeastern USA. Oral transmission of the parasite may have
occurred as a result of this behavior.
PMID- 9638622
TI - Recovery rates, serotypes, and antimicrobial susceptibility patterns of
salmonellae isolated from cloacal swabs of wild Nile crocodiles (Crocodylus
niloticus) in Zimbabwe.
AB - Samples from the cloaca and the ventral skin surface of 67 Nile crocodiles
(Crocodylus niloticus) captured in four uninhabited areas at Lake Kariba,
Zimbabwe, were cultured for Salmonella. All the skin samples tested negative for
Salmonella, whereas 18 of 67 (26.9%) cloacal samples grew Salmonella.
Significantly more males than females yielded Salmonella, but no statistically
significant correlation among salmonella carriage, body size, and age was
recorded. Ten different serotypes of S. enterica belonging to the subspecies
enterica, salamae, and diarizonae were isolated. All isolates belonging to
subspecies enterica displayed invasive properties in an experimental mouse model
and thus exhibited pathogenic potential, whereas none of the other isolates were
invasive. In general, isolates were sensitive to a number of commonly used
antimicrobials, except for three isolates that were resistant to streptomycin.
PMID- 9638623
TI - Malignant seminoma with metastasis and herpesvirus infection in a free-living sea
otter (Enhydra lutris).
AB - In winter 1990, an adult male sea otter (Enhydra lutris) was found dead along the
eastern shore of Prince William Sound, Alaska. Necropsy findings included an
enlarged retained left testicle with a twisted spermatic cord, enlarged left
sublumbar lymph node, emaciation, dental attrition, oral papules and ulcers, and
luminal intestinal hemorrhage associated with numerous acanthocephalids. A
malignant seminoma was present in the left testicle and left sublumbar lymph
node. Additionally, herpesvirus like intranuclear inclusion bodies were found in
oral, esophageal, and corneal epithelial cells. Virions consistent with a
herpesvirus were found in esophageal epithelium. Dental attrition, severe
intestinal acanthocephaliasis, the malignant seminoma, and emaciation were
considered contributing factors in causing death. The herpesviral disease was
probably secondary to the debilitation and stress. This is the first report of
malignant seminoma with metastasis in a sea otter.
PMID- 9638624
TI - Effects of lithium heparin and tripotassium EDTA on hematologic values of
Hermann's tortoises (Testudo hermanni).
AB - In an effort to define the effect(s) of lithium heparin and tripotassium EDTA on
various hematologic parameters in Testudo hermanni, we collected blood samples
from 29 clinically healthy adult individuals of both sexes. Portions of each
blood sample were transferred to tubes containing either lithium heparin or
tripotassium EDTA. The following determinations were made on samples of blood
from each anticoagulant: red and white cell counts, packed cell volume,
hemoglobin concentration, red cell indices, and differential white cell counts.
Due to hemolysis, hematocrits could not be determined from blood samples in EDTA.
Further, red blood cell counts were lower in the EDTA samples than in the heparin
samples, again due to hemolysis associated with EDTA. However, EDTA did not
appear to interfere with hemoglobin determinations. Heparin blood samples
provided more optimal blood smears than did EDTA samples, thus differential
leucocyte counts were determined only from smears taken from heparin blood
samples. Further, thrombocyte and leucocyte aggregation was not observed with
heparin use. Thus, heparin is considered the anticoagulant of choice in
chelonians for determining red blood cell counts, erythrocyte indices, and
hematocrits. When May-Grunwald-Giemsa stain was compared with Diff-Quick,
thrombocytes could be more easily differentiated from lymphocytes using the May
Brunwald-Giemsa stain. Heterophil granules seemed to coalese more when Diff-Quick
was used. Eosinophils, basophils, and monocytes were similar in appearance with
both staining methods.
PMID- 9638625
TI - Chemical restraint of the Nile hippopotamus (Hippopotamus amphibius) in
captivity.
AB - This retrospective study describes 16 immobilizations performed on nine adult
captive Nile hippopotamus (Hippopotamus amphibius). Animals were immobilized
using intramuscular etorphine alone (1.0-5.0 micrograms/kg; n = 9) or in
combination with xylazine (67-83 micrograms/kg; n = 6) or acepromazine (20
micrograms/kg; n = 1). Exact weights for the animals were unknown so drug dosages
were based on estimated weights. Seven animals either were in good health or had
minor or localized medical problems. Following etorphine and xylazine induction,
one animal undergoing castration was anesthetized with isoflurane in oxygen
delivered by endotracheal tube. Ten immobilizations occurred without
complications, and eight of those procedures were rated as good or excellent.
Complications, including bradypnea, cyanosis, and apnea, occurred during six
immobilizations. One animal died following prolonged apnea, and the necropsy
failed to find a specific cause of death. Immobilizations were reversed with
diprenorphine alone (4.4-10.0 micrograms/kg; n = 13), diprenorphine (2.9
micrograms/kg) and naloxone (14.6 mu k/kg; n = 1), or naltrexone (146-180
micrograms/kg; n = 2). Mean time to reversal of immobilization for those animals
given etorphine alone and reversed with diprenorphine alone was 21.6 min (n = 5).
Time to reversal for the two immobilizations reversed with only naltrexone was 4
min. No renarcotizations were observed. Total doses of 2.0-6.0 mg etorphine i.m.
should produce heavy sedation to surgical anesthesia in calm adult captive Nile
hippopotamuses. Insufflation with oxygen during immobilization seems warranted.
PMID- 9638626
TI - Presumptive dirofilariasis in a pale-headed saki monkey (Pithecia pithecia).
AB - A 6-yr-old male pale-headed saki monkey (Pithecia pithecia), born at the Dallas
Zoo, reentered the collection in 1994 after it was housed for 4 yr in Rhode
Island and 2 yr in Florida. The monkey tested negative for both Dirofilaria
immitis microfilariae and D. immitis adult antigens (via commercially available
tests) upon return. However, it tested positive for adult antigens 1 yr later,
and additional testing, including ultrasonography, suggested a diagnosis of
aberrant dirofilariasis. Relevant evidence of previous microfilaremia in pale
headed saki monkeys at the Dallas Zoo is reviewed. Dirofilaria immitis infection
should be included in the differential diagnosis list for any nonhuman primate
with cardiopulmonary disease wherever the parasite is enzootic.
PMID- 9638627
TI - Fatal acute toxoplasmosis in three golden lion tamarins (Leontopithecus rosalia).
AB - Fatal acute toxoplasmosis was diagnosed in three golden lion tamarins
(Leontopithecus rosalia), a breeding pair and their male offspring, by histology
and immunohistochemistry. The distribution and severity of lesions differed among
the animals, but the small intestine and the pancreaticoduodenal lymph nodes were
especially affected. Protozoal organisms consistent with Toxoplasma gondii
tachyzoites, often clustered, were seen in all lesions and were specifically
immunostained with a T. gondii polyclonal antibody. The infection was probably
acquired orally. Several breeding groups of golden lion tamarins have succumbed
to toxoplasmosis both in North American and European zoos, so this disease should
be considered an important problem in this endangered species. Toxoplasma gondii
can cause latent infections in New World primates and therefore could potentially
induce abortions or congenital infections in wild golden lion tamarins born from
latently infected reintroduced females.
PMID- 9638628
TI - Isolation of a herpes simplex virus type 1-like agent from the brain of a
mountain agile gibbon (Hylobates agilis agilis) with encephalitis.
AB - A captive-born 2-yr-old male mountain agile gibbon (Hylobates agilis agilis) that
died of encephalitis harbored a herpes simplex virus type 1 (HSV1)-like agent in
the brain. A complete necropsy revealed intensive meningeal congestion with
nonsuppurative encephalitis. The virus was recovered from frozen brain tissue in
Vero cells. The isolate was very similar but not identical to human HSV1. Both
western blot assay and virus neutralization tests were done with sera from 15
gibbons. Antibodies against HSV1 and herpes simplex virus type 2 (HSV2) were
detected in four healthy gibbons, which included four species in three subgenera.
PMID- 9638629
TI - Agenesis of a radius in a polar bear cub (Ursus maritimus).
AB - A polar bear (Ursus maritimus) cub, delivered by a cesarean section, was
diagnosed with congenital agenesis of the radius on the basis of clinical
presentation and radiology. A specific etiology could not be ascertained.
Agenesis of the radius has not been previously reported in any nondomestic
species.
PMID- 9638630
TI - Granulomatous hepatitis associated with Hepatozoon sp. meronts in a southern
water snake (Nerodia fasciata pictiventris).
AB - A wild-caught adult female southern water snake (Nerodia fasciata pictiventris)
did poorly in captivity. A peripheral blood-film examination demonstrated
numerous hemogregarines characterized as fusiform nondividing intraerythrocytic
gametocytes. Xenodiagnostic typing in laboratory-reared mosquitoes demonstrated
the parasite to be of the genus Hepatozoon. Gross and histopathologic examination
of the liver demonstrated numerous granulomas centered on groups of one to six
Hepatozoon sp. meronts, an unusual finding in naturally infected wild-caught
snakes.
PMID- 9638631
TI - A fibrosarcoma in a Siamese crocodile (Crocodylus siamensis).
AB - A fibrosarcoma of periosteal origin was identified in the oral cavity of a 22-yr
old male captive Siamese crocodile (Crocodylus siamensis). The diagnosis was
based upon the gross and light microscopical examination. The mesenchymal
histogenesis was derived from the capability of the cells to produce collagen
fibers. The invasive growth and the polymorphous cells in combination with the
low mitotic index suggest a low-order malignancy. Attempts by immunohistochemical
staining techniques to identify the specific lineage of the neoplastic cells and
the expressed collagen type were unsuccessful.
PMID- 9638632
TI - A fatal Pegosomum sp. (Trematoda: Echinostomatidae) infection in a wild cattle
egret (Bubulcus ibis) from Japan.
AB - An adult cattle egret (Bubulcus ibis) caught in Kobe of Hyogo Prefecture, Japan,
in December 1995 died of a severe infection associated with the trematode
parasite Pegosomum sp. At necropsy, 22 trematode parasites were found in the
lumen of the bile duct, and the duct wall was markedly thickened.
Histopathologically, severe cholangitis and cholecystitis were observed in close
association with the parasites in the bile duct. Severe Pegosomum sp. infection
may be one of the factors contributing to the mortality of wild cattle egrets.
This is the first reported case of the genus Pegosomum infection in wild birds of
Japan.
PMID- 9638633
TI - Metastatic malignant mesothelioma in a tiger (Panthera tigris).
AB - An 8-yr-old female tiger (Panthera tigris) died following a 2-wk history of
progressive depression, anorexia, respiratory insufficiency, and exercise
intolerance. At the time of necropsy, numerous coalescing, 4-20-mm, tan, firm
nodules were scattered throughout the pleural surfaces of the thoracic wall and
the mediastinum, giving a velvety appearance to these surfaces. Histologically,
the nodules were diagnosed as malignant pleural mesothelioma. Secondary
metastasis to the regional tracheobronchial and mediastinal lymph nodes was
observed.
PMID- 9638634
TI - Squamous cell carcinoma in an immature common stork (Ciconia ciconia).
AB - An immature common stork (Ciconia ciconia) was referred from the Wildlife
Recovering Center to the Department of Surgery for evaluation. Physical
examination revealed a partially ulcerated, necrotic mass on the left surface of
the upper beak. The mass was surgically removed and classified histologically as
a squamous cell carcinoma. Postsurgically, the bird recovered uneventfully and
proceeded to mature normally. During this growth period, no tumor recurrence or
metastasis was detected, and no local bone alteration to the beak was found. The
stork was ringed and released back into its natural environment.
PMID- 9638635
TI - Clinical challenge. Internal hydrocephalus.
PMID- 9638636
TI - Lung cancer: therapeutic modalities and cytoprotection.
AB - Lung cancer is the leading cancer killer in the United States today. The current
methods of treatment, radiation and various chemotherapies, have been used with
some success; however, early detection remains the key to successful therapy.
Current clinical trials indicate that an improvement of available therapies is
needed. Consequently, the development of new approaches to treatment is foremost
in the minds of researchers. Advances in molecular medicine have produced new
drugs that can protect normal cells from chemotherapy-induced toxicities,
resulting in enhanced drug delivery with few dose reductions. This review will
discuss some of the advances that have been made in understanding the molecular
biology of lung cancer as well as the current and most promising methods of
treatment used for various forms of lung cancer. The potential contribution of
cytoprotectors to enhance the safety and effectiveness of these therapies will be
examined.
PMID- 9638637
TI - Induction of manganese superoxide dismutase gene expression in bronchoepithelial
cells after rockwool exposure.
AB - Superoxide dismutases play an important protective role in the lung defense
against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers).
Particularly crocidolite, but also other asbestos fibers, are known to induce
cellular antioxidant defense. Although rockwool, a man-made fiber made from rock,
is used widely for insulation purposes, its effects on the superoxide dismutases
in bronchoepithelial cells have not been investigated. Thus, the purpose of this
study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to
rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA
and an increase of MnSOD activity levels. The results were compared with BEAS 2B
cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale
Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50
micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control
fibers. Scanning electron microscopy confirmed close dust cell contact under all
experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p
< 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2.
However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but
not in rockwool-exposed cells decreased. Slight (no significance) increases of
MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2)
concentrations. These results suggest that: (1) like crocidolite and silica,
rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an
increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3)
in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of
crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because
oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of
active MnSOD protein may be caused by inactivation on a post-translational level.
Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with
increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD
gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial
cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic
in this experimental setting.
PMID- 9638638
TI - Effects of halothane, enflurane, isoflurane, and sevoflurane on slowly adapting
pulmonary stretch receptor activity in anesthetized dogs.
AB - The aim of this study was to evaluate the effects of halothane, enflurane,
isoflurane, and sevoflurane on slowly adapting pulmonary stretch receptor (SAR)
activity in dogs. Eight beagles were anesthetized with an intravenous injection
of a mixture of urethane and alpha-chloralose as a basal anesthesia, then
vagotomized, artificially ventilated, and chest opened. Single afferent
activities from SARs were recorded from the peripheral nerve cut end of the left
vagus. Changes in SAR activities with inhalation of halothane, enflurane,
isoflurane, and sevoflurane at 1, 1.5, and 2 times the minimal alveolar
anesthetic concentration (MAC) were measured, and differences in the discharges
within and among four anesthetics were evaluated. As a result, two different
types of SARs, low threshold SARs and high threshold SARs, were detected in this
study. In all anesthetics, expiratory discharges of low threshold SARs decreased
significantly in a dose-dependent manner, whereas inspiratory discharges did not
change significantly at any anesthetic level. Discharges of high threshold SARs
tended to decrease with increasing anesthetic level; however, no statistical
significance was observed at any anesthetic level. Only one exception to these
changes was observed at 1 MAC of halothane where no significant decrease in the
expiratory discharge of low threshold SARs or significant increase in the
discharge of high threshold SARs was induced against a control value. In
conclusion, recent inhalation anesthetics, except for halothane at the light
anesthetic level, tended to decrease SAR activities depending on the anesthetic
level, suggesting attenuation of the Hering-Breuer inflation reflex.
PMID- 9638639
TI - Changes in pulmonary mechanics after lung volume reduction surgery.
AB - Lung volume reduction surgery (LVRS) is a promising new treatment for emphysema
and leads to increased flow rates. We investigated the mechanisms by which flow
rates could increase and the correlates of lessened dyspnea in patients
undergoing LVRS before and 3 months after LVRS in patients with severe emphysema.
The following were done: routine pulmonary function testing, measurements of
elastic recoil (Pel), tidal breathing patterns, inspiratory work of breathing
(Winsp), construction of static recoil-maximum flow curves, and measurement of
baseline and transitional dyspnea index (TDI). There were increases in forced
vital capacity (FVC: 2.24 +/- 0.71 to 2.92 +/- 0.63 liters; p < 0.05), forced
expired volume in 1 (FEV1: 0.64 +/- .16 to 1.03 +/- 0.28 liters; p < 0.01), and
decreases in all divisions of lung volume, e.g. total lung capacity (TLC: 6.86 +/
1.41 to 5.96 +/- 1.49 liters; p < 0.01). Maximum Pel increased (11.7 +/- 3.7 to
19.8 +/- 7.8 cmH2O; p < 0.02) as did the coefficient of retraction (CR = Pel/TLC:
1.8 +/- 0.7 to 3.6 +/- 3.6 +/- 2.2 cmH2O/liter). However, the individual
responses in other parameters were markedly different among patients. There was
no consistent trend in changes in the slope or position of the static recoil
maximum flow curve or Winsp. The only positive correlate of improved dyspnea (TDI
= 3.22 +/- 2.22; p < 0.01) was improvement in CR, FEV1 being a weak negative
correlate and change in lung volume not being a correlate at all. We conclude
that there is a heterogeneous response of the airways to LVRS. Increased elastic
recoil was the primary determinant of improved flow rates after LVRS and is the
only positive correlate for improvement in dyspnea.
PMID- 9638640
TI - Isoniazid levels in the bronchoalveolar lavage fluid of patients with pulmonary
tuberculosis.
AB - Isoniazid (INH) is one of the most important first line drugs in the treatment of
tuberculosis. We utilized high performance liquid chromatography with a hydrazone
extraction technique to measure INH in bronchoalveolar lavage (BAL) fluid
specimens from six patients with active pulmonary tuberculosis. We found BAL
fluid INH levels to be similar to 2-h peak serum levels. The concentration of INH
in BAL fluid from lobes with infiltrate was similar to the concentration of INH
in BAL fluid from lobes without infiltrate (0.062 microgram/ml and 0.073
microgram/ml, respectively). After adjusting for protein concentration in the BAL
fluid, INH levels in lobes with infiltrate were threefold lower than in lobes
without infiltrate. The correlation between the concentration of INH in serum and
BAL fluid approached significance after correcting for protein (lobes with
infiltrate, r2 = 0.60 (p = 0.07); lobes without infiltrate, r2 = 0.50 (p = 0.12).
INH penetrates into bronchoalveolar fluid, and concentrations of INH in the BAL
fluid suggest that assessment of the INH serum concentration is adequate to
evaluate bioavailability of the drug in patients with pulmonary tuberculosis.
PMID- 9638641
TI - Experimental hypersensitivity pneumonitis: location of transferring cells.
AB - Cultured cells from Micropolyspora faeni-sensitized donors can adoptively
transfer murine experimental hypersensitivity pneumonitis (EHP). We sought to
determine the location of transferred cells in recipient animals, the influence
of the origin of the cultured cells, and the effect of specific intratracheal
challenge. We labeled cultured sensitized spleen or lung-associated lymph node
(LALN) cells with CFDA-SE, a cytoplasmic stain, before transfer to naive
recipients, which were sacrificed 1 h, 1 day, or 4 days thereafter. We also
transferred labeled cultured spleen cells to recipients that were challenged with
intratracheal M. faeni and sacrificed 4 days later (MF). Controls were recipients
of M. faeni-sensitized and cultured cells challenged with intratracheal normal
saline (NS) and recipients of ovalbumin (OVA)-sensitized cells cultured with M.
faeni and challenged with intratracheal M. faeni (OVA). The number and proportion
of cells that were stained were determined in dispersed spleen, peripheral and
lung-associated lymph nodes, and lung parenchyma. The extent of the pulmonary
inflammatory response was measured by determining the proportion of microscopic
fields that were abnormal and the total number of dispersed pulmonary cells. CFDA
SE stained cells uniformly, and stained cells could be detected in recipients for
up to 7 days after transfer. CFDA-SE treatment (0.5 microM) did not affect the
ability of cells to transfer EHP adoptively. Transferred cells could be detected
easily in lung, lung-associated and peripheral lymph nodes, blood, and spleen.
Transferred cells localized to the lung at 1 h but then rapidly decreased with no
difference between labeled cells from spleen and LALN. After intratracheal M.
faeni challenge, there was no difference in the proportion of labeled cells in
the lung among any of the groups (MF, NS, or OVA). There was an increase in the
number of lung cells in the MF group compared with the control (NS and OVA)
groups. We conclude that cells capable of transfer are transiently (1 h) trapped
in the lung but are much decreased in the lung by four days after transfer. After
intratracheal antigen challenge of recipients, there is a substantial increase in
the number of pulmonary cells in animals exhibiting adoptive EHP but not in the
control groups. Transferred cells responsible for EHP are increased in the lungs
of animals with adoptive EHP.
PMID- 9638642
TI - Cloning and characterization of a tobacco cDNA encoding calcium/calmodulin
dependent glutamate decarboxylase.
AB - In plants, gamma-aminobutyric acid (GABA), a major transmitter in the central
nervous system in animals, is synthesized by glutamate decarboxylase (GAD), the
activity of which is tightly modulated by Ca2+/calmodulin. To study the molecular
mechanism of GAD regulation and examine the physiological role of GABA in plants,
we isolated and characterized a 1771 bp tobacco cDNA clone, pNtGAD2. The 496
amino acid sequence deduced from pNtGAD2 showed 97, 92, and 81% identity to
NtGAD1, petunia, and tomato GAD, respectively. The 26 amino acid sequence within
the putative calmodulin binding domain at the carboxy terminus showed a typical
alpha-helical structure with hydrophobic and charged amino acid clusters. The
pNtGAD2-encoded 56 kDa protein interacted strongly with a monoclonal antibody
against the petunia GAD and its GAD activity was stimulated markedly by the
addition of exogenous calcium and calmodulin. The molecular sequence of pNtGAD2
and biochemical characteristics of the pNtGAD2-encoded protein confirmed that
pNtGAD2 is a clone encoding a functional calmodulin-binding and Ca2+/calmodulin
dependent tobacco glutamate decarboxylase. This result indicates that tobacco
plants also have Ca2+/calmodulin-dependent GADs.
PMID- 9638643
TI - Saccharomyces cerevisiae STE11 may contribute to the stabilities of a scaffold
protein, STE5, in the pheromone signaling pathway.
AB - Saccharomyces cerevisiae STE5 is an essential component of the pheromone-mediated
mitogen activated protein kinase (MAPK) pathway. The STE5 protein recruits MAPK
module kinases (STE11, STE7, and FUS3) to give a specificity for the pheromone
pathway. The STE5 protein contains a putative PEST motif for ubiquitin-dependent
protein degradation, and its level may be important for regulation of pheromone
signal transduction. In this article, we studied the roles of proteins associated
with the STE5 protein for its stabilization by analyzing ste deletion mutants.
Here, we found that the STE11 kinase performed the most important role in
stabilization of the STE5 protein. The level of STE5 protein was significantly
low in the absence of STE11 kinase, suggesting essential roles of STE11 in
stabilization of the STE5 protein. Immunodetection and Northern blot analyses
showed that the low level of the STE5 protein in the ste11 delta mutant is not
due to the level of gene expression but to that of protein stability. Measurement
of relative binding affinities showed that the STE11 protein tightly interacts
with the STE5 protein for its stabilization.
PMID- 9638644
TI - Spinach cytosolic fructose-1,6-bisphosphatase: I. Its organ-specific and
developmental expression characteristics.
AB - Spinach (Spinacia oleracea) cytosolic fructose-1,6-bisphosphatase (FBPase) was
purified and the final preparation of protein has a specific activity of about 45
units/mg protein and a single band of molecular mass of 39 kDa. Polyclonal
antibody against the protein did not cross-react with chloroplast FBPase, but
showed strong cross-reactivity with all plant cytosolic FBPases tested. Studies
of the FBPase expression characteristics at early stages of development
demonstrated that it was controlled at both the transcriptional and translational
levels, and its mRNA was detected even in etiolated cotyledons. This suggests
that the expression is not light-inducible. A single transcript was detected in
all spinach tissues tested. Western blot analysis revealed two protein bands in
the etiolated cotyledons: one was the same size as that present in the mature
leaf, and the other slightly smaller. A high enzyme activity was detected in
etiolated cotyledons, especially compared to protein levels in Western blots.
Expression of the cytosolic FBPase gene during leaf development showed no change
in the steady-state level of mRNA, but the protein level and enzyme activity were
higher in mature leaves than in young ones, suggesting that the increase in
FBPase activity during development is due to an increase in protein synthesis.
Young roots showed low enzyme activity, but an unexpectedly high activity was
detected in old fiber roots.
PMID- 9638645
TI - Spinach cytosolic fructose-1,6-bisphosphatase: II. Light effect on its
expression.
AB - The effect of light on the expression of spinach (Spinacia oleracea) cytosolic
fructose-1,6-bisphosphatase (FBPase) was determined by the level of mRNA, protein
content, and enzyme activity. It was found that its expression and activity were
constant and stable during normal daily conditions as well as under continuous
light or dark conditions. However, two different mRNAs were detected; one
transcript was expressed all the time, while the other was detected only during
prolonged dark periods. Analysis of the expression of the mRNAs at the protein
level using an activity gel showed that this "darkness-specific" mRNA encoded a
separate, distinct polypeptide. Thus, our data suggest that cytosolic FBPase is
encoded by a small multigene family.
PMID- 9638646
TI - Top DNA polymerase from Thermus thermophilus HB27: gene cloning, sequence
determination, and physicochemical properties.
AB - A gene, top encoding Thermus thermophilus HB27 (Top) DNA polymerase, was cloned
in E. coli and its nucleotide sequence was determined. Based on its deduced amino
acid sequence, Top DNA polymerase is a 93.8 kDa protein comprising 834 amino acid
residues. Top DNA polymerase showed high amino acid homology with those of other
DNA polymerases from the Thermus sp., for example, 87.3% identity with Taq DNA
polymerase. Codon usage in the top gene was similar to those of the proteins from
other Thermus strains. The G + C content in the third position of the codons was
as high as 93%. The top gene under the control of the tac promoter was expressed
in E. coli [plasmid pTOP9]. DNA amplification using the recombinant Top DNA
polymerase performed the same as other thermostable DNA polymerases from Thermus
strains. The optimum temperature for its reaction was 76 degrees C. An
interesting observation was that the recombinant Top DNA polymerase was slowly
cleaved into two fragments of about 60 kDa and 35 kDa at 4 degrees C and -20
degrees C. The larger fragment possessed polymerase activity like the Klenow
fragment of E. coli DNA polymerase I. To prevent the cleavage of the Top DNA
polymerase, a variety of protecting agents were examined. Among those examined,
(NH4)2SO4 (100 mM) solution demonstrated an outstanding ability to block its
cleavage for a prolonged period.
PMID- 9638647
TI - Characterization of Mas-7-induced pore formation in SK-N-BE(2)C human
neuroblastoma cells.
AB - Mastoparan, a peptide toxin from wasp venome, mimics receptors by stimulating the
GTPase activity of guanine nucleotide binding proteins and the G-protein-coupled
phospholipase C (PLC). By using Mas-7, the active analog of mastoparan, we showed
that it makes pores in the plasma membrane. Treatment with Mas-7 but not Mas-17,
the inactive analog, produced a concentration-dependent rise in intracellular
Ca2+ concentration ([Ca2+]i) and facilitated the uptake of ethidium bromide
(EtBr) (314 Da) to a sustained level during the stimulation. In addition, Mas-7
triggered the influx of lucifer yellow (457 Da), while it did not induce the
influx of fura-2 (831 Da) and Evans blue (961 Da). However, the Mas-7-induced
permeability was selectively prevented by the addition of La3+, Ni2+, and Co2+,
but not Cd2+. This blocking activity was concentration-dependent. While the
stimulatory effect of Mas-7 on PLC activity was dependent on extracellular Ca2+,
the pore forming activity of Mas-7 was not effected by removal of extracellular
Ca2+. These results, therefore, suggest that the mastoparan's action in pore
formation is independent from its action in PLC stimulation and is negatively
effected by inorganic cations.
PMID- 9638648
TI - Development of a new anti-CD4 monoclonal antibody (YG23) which inhibits the
formation of colonies of human bone marrow progenitor cells.
AB - We have previously reported CD4 expression in CD34+ hematopoietic progenitor
cells and suggested a role of CD4 in normal hematopoiesis and its possible
relationship with the pathogenesis of acquired immunodeficiency syndrome (AIDS).
To investigate whether CD4 expression in bone marrow progenitor cells can explain
bone marrow suppression in AIDS, monoclonal antibodies (mAbs) against human CD4
were developed by immunizing Balb/c mice with human thymocytes. Three mAbs
completely blocked the binding of Leu3a antibody, a well-known anti-CD4 mAb, to
thymocytes, which indicates overlap between the epitopes recognized by these and
Leu3a antibodies. Interestingly, one of these mAbs, YG23, significantly inhibited
colony formation of human bone marrow progenitor cells treated with GM-CSF. This
is the first demonstration that ligation of CD4 by an anti-CD4 mAb suppresses GM
CSF mediated proliferation and differentiation of human hematopoietic progenitor
cells by modifying the intracellular signaling pathway through CD4 molecules.
Based on these findings, we propose that alteration of CD4 signaling by either
cross-linked gp120 or antibodies directed against a certain epitope shared with
the YG23 binding site of the CD4 molecule may play a role in bone marrow
dysfunction in AIDS patients.
PMID- 9638649
TI - Sequencing and chromosomal localization of the RA138 gene encoding a rice
allergenic protein.
AB - A cDNA clone (RA138) encoding a rice allergenic (RA) protein has been isolated
during a large-scale random sequencing of a cDNA library prepared from developing
seeds. The nucleotide sequence of the RA138 gene contained an open reading frame
(ORF, 477 bp) encoding a 17 kDa protein. The amino acid sequence deduced from the
ORF was composed of 159 amino acid residues and was highly homologous to those
from RA genes previously isolated, such as RA5 (92% identity), RA14 (73%), and
RA17 (68%). The protein contained 10 cysteine residues that were conserved in the
alpha-amylase/trypsin inhibitor family including RA proteins. Excluding a
putative signal peptide consisting of 26 amino acid residues, the mature protein
would be 14.4 kDa in size and have a pI of 7.0. DNA gel blot analysis under high
stringency conditions indicated that multiple copies of the RA138 gene were
present in the rice genome. The chromosomal location of the RA138 gene has been
identified on chromosome 7 in a segregation analysis using a population of 164
recombinant inbred lines derived from a cross between Milyang 23 and Gihobyeo.
The locus that may contain multiple copies of the RA138 was located between RFLP
markers RG477A and C492 with genetic distances of 10.7 cM and 6.7 cM,
respectively.
PMID- 9638650
TI - Genome characterization of a Korean isolate of cymbidium mosaic virus.
AB - The complete nucleotide sequence of the genomic RNA of a Korean isolate of
cymbidium mosaic virus (CymMV-K2) was determined. The genomic RNA is 6227
nucleotides in length, excluding the poly(A) tail. It contains a 5'-noncoding
region (NCR) of 73 nucleotides, five open reading frames (ORFs 1 to 5) which
encode proteins with M(r) 160 kDa RNA-dependent RNA polymerase (ORF1), 26 kDa
movement protein 1 (ORF2), 13 kDa movement protein 2 (ORF3), 10 kDa movement
protein 3 (ORF4), 24 kDa coat protein (OFR5), and a 3' NCR of 76 nucleotides. The
5'-end of the CymMV-K2 genome initiates with GGAAAA which contrasts to GAAAA at
the 5'-ends of other potexviruses, including a Singapore isolate of CymMV (CymMV
S2). When compared with CymMV-S2, 171 base substitutions were observed in the
CymMV-K2 genome. Substitutions in the overlapping ORFs (ORFs 2 to 4) occurred
more frequently than those in 5' NCR, ORF1, and 3' NCR. In addition to
substitutions, two single-base deletions, one in the intercistronic region
between ORF1 and ORF2 and the other in the ORF2, were found on the CymMV-K2
genome. The deletion in the ORF2 induced a frameshift which altered the C
terminal domain of movement protein 1. ORF3 and ORF4 of the CymMV-K2 genome are
partially different from those of another Singapore CymMV genome (CymMV-S1) which
has four frameshifts due to nucleotide deletions within these ORFs.
Interestingly, the frameshifts resulted in no change in the conserved sequences
of the movement proteins but reconstructed their transmembrane domains.
PMID- 9638651
TI - High level accumulation of an aberrantly spliced human DHFR RNA species.
AB - Cells transduced with either of two human DHFR minigenes express an RNA product
which is considerably shorter than what would be predicted from the size of an
unspliced transcript expressed from its DNA template. RNA blotting analysis has
shown that this short transcript accumulated to exceedingly high levels which
were comparable to the levels reached by the highly abundant endogenous actin
mRNA, or MoMLV RNA expressed in chronically infected cells. RNA blotting, RNase
mapping, primer extension, RT-PCR, and sequencing have shown that this highly
expressed transcript, termed TBN, is a spliced RNA product which utilizes cryptic
splice signals present in the normally spliced DHFR mRNA. Subcloning experiments
have demonstrated that all the information required for the generation and high
level accumulation of the TBN transcripts is encoded in the 1.6 kb DHFR DNA
minigene. TBN transcripts were generated with comparable efficiency from DNA
templates containing either the human ADA or the early SV40 promoters. Since
neither the ADA nor the SV40 promoter are considered to be particularly "strong"
promoters, this observation argues that initiation of transcription is not the
rate limiting step in determining the amount of the TBN transcripts which
accumulate in the cell. Insertion of a foreign sequence into the DHFR DNA
minigene led to the expression and high level accumulation of a chimeric
transcript, suggesting that the unusual properties of this expression system may
be used for high level expression of foreign sequences. These observations offer
new insights into the mechanisms which control the accumulation of translatable
mRNA in the cell, and have potentially important implications for experiments
involving optimization of gene expression for gene therapy applications.
PMID- 9638652
TI - Increased expression of the gentamicin resistance gene by a Tn3 sequence located
at the upstream region.
AB - Recombinant plasmids designated as pCH1 and pCH21 were constructed to determine
the influence of the bla sequence on the expression of the gentamicin resistance
gene which is located downstream of Tn3. Minimal inhibitory concentration (MIC)
test and Northern hybridization results with the constructed plasmids showed that
the transcription of the gentamicin resistance gene was initiated from the
promoter, located downstream from the PstI site within the bla gene, and the
hybrid promoter created by IR sequences of Tn3. Although the read-through
transcription from the bla promoter did not occur, the transcription of the bla
gene increased the expression of the gentamicin resistance gene.
PMID- 9638653
TI - Effects of dopamine and estrogen on the regulation of Pit-1 alpha, Pit-1 beta,
and PL-II gene expression in the rat placenta.
AB - Pituitary-specific transcription factor Pit-1 regulates growth hormone and
prolactin gene expression in the pituitary. Recently, Pit-1 was shown to be
locally synthesized in the rat placenta and is involved in the regulation of rat
placental lactogen (PL) gene expression. Pit-1 has three different splicing
variants. They are well known as being biologically active. In the present study,
we found that Pit-1 beta is also synthesized in the rat placenta and we tried to
examine the effects of dopamine and estrogen on the regulation of Pit-1 alpha,
beta and PL-II genes expression using the reverse transcription-polymerase chain
reaction (RT-PCR) and Northern blot hybridization. A dopamine receptor agonist,
bromocriptine, significantly decreased placental Pit-1 alpha, beta, and PL-II
mRNA levels. To examine the effect of estrogen on the gene expression of Pit-1
beta, pregnant female rats were ovariectomized (OVX) and injected daily with 17
beta-estradiol. OVX markedly lowered the amount of Pit-1 beta mRNA. Estrogen
injection recovered the OVX-induced inhibition of Pit-1 beta mRNA level. Finally,
we investigated the site-specific transcription of Pit-1 alpha and beta mRNA in
the labyrinth zone and junctional zone of the placental in 15 and 20 days of
gestation. The main site of Pit-1 alpha and beta synthesis was shifted from the
junctional zone to the labyrinth zone from 15 to 20 days of gestation. Together,
these data presume that Pit-1 beta may play a more important role in the placenta
than in the pituitary and that Pit-1 may be involved in the regulation of the PL
and prolactin-like peptide by estrogen and dopamine in the rat placenta.
PMID- 9638654
TI - Identification of differentially expressed genes in human hepatoblastoma cell
line (HepG2) and HBV-X transfected hepatoblastoma cell line (HepG2-4x).
AB - Hepatitis B virus-X protein (HBV-X) is known to be an important factor in the
formation of hepatocellular carcinoma by acting as a transcriptional activator on
viral or cellular genes. To identify differentially expressed genes between the
human hepatoblastoma cell line HepG2 and HBV-X gene transfected hepatoblastoma
cell line HepG2-4X, we used a differential display polymerase chain reaction
technique. The technique produced numerous up-regulated and down-regulated bands,
each representing a partial cDNA fragment. We isolated 23 different kinds of cDNA
fragments that showed marked differences in two cell lines. The fragments were
used as templates for DNA sequencing analysis and as probes for Northern blot
analysis. This analysis revealed that eight cDNA clones were differentially
expressed in each cell line but fifteen cDNA clones were not. Among the 8 clones,
3 clones showed sequence similarities with human mitochondrial ATPase subunit 6
(mtATPase 6) and the human amidophosphoribosyl transferase (ATase) precursor,
whereas 5 other clones were human novel protein encoding genes. Two genes having
similarity with known genes were repressed by HBV-X. These results reflect that
complex alterations of the expression of enzymes concerning the energy-generating
system in mitochondria and metabolite synthesis are closely associated with the
HBV-X function during the formation of hepatocellular carcinoma. These newly
obtained genes will be useful for analyzing HBV-X functions. We are in the
process of further characterizing these genes.
PMID- 9638655
TI - Sequence analysis and expression of Met-rich storage protein SP-1 of Hyphantria
cunea.
AB - We isolated and sequenced a cDNA clone corresponding to the 2.5 kb storage
protein (SP-1) from fall webworm, Hyphantria cunea. The SP-1 gene encoded a pre
protein of 753 amino acids, including a signal peptide of 15 amino acids. The
deduced amino acid sequence of SP-1 contained one potential N-glycosylation site,
and the calculated isoelectric point and molecular weight of secreted SP-1 were
pI = 8.38 and 86.8 kDa, respectively. A Northern blot of mRNA from various
developmental stages revealed that the SP-1 mRNA in fat body appears in early
last instar larvae and accumulates to a maximum level at the end of last instar
larvae. The persistence of SP-1 transcript through the early pupal stage suggests
that its mRNA might be stable or expressed during the pupal stage. SP-1
transcription was also found in the ovary as well as testis. This local
expression of SP-1 in both reproductive organs seems to allow the insect to keep
its reproductive activity under a nutritional stress.
PMID- 9638656
TI - Sequence variation of EBNA2 of Epstein-Barr virus isolates from Korea.
AB - To reveal sequence variations in the Epstein-Barr virus nuclear antigen 2 (EBNA2)
genes of Epstein-Barr virus (EBV) strains circulating in the Korean population,
the EBNA2 divergent region was amplified and sequenced from 13 EBV-1 isolates, 2
EBNA2 type 1 intertypic EBV isolates, and two EBV-2 isolates, all derived from
Korean cancer patients. Comparative sequence analysis revealed that type 1 and
type 2 EBNA2 divergent regions of Korean EBV isolates were almost identical to
the respective regions of the B95-8 EBV-1 and AG876 EBV-2 strains. Two of the
nucleotide changes found in the type 1 divergent regions of all Korean isolates,
G-to-T and C-to-A at B95-8 EBV positions 48,991 and 48,998, respectively, are
also present in all EBV-1 strains of non-Asian origins, indicating that these two
sites might be mutational hot sites. Besides these two mutations, EBV-1 strains
from Papua New Guinea or European Caucasians and Africa show unique patterns of
identical sequence variations from B95-8, which were not found in type 1 isolates
from Korea, suggesting that Korean type 1 are evolving as a lineage distinct from
isolates from Papua New Guinea or European Caucasian and Africa.
PMID- 9638657
TI - Cholesterol biosynthesis from lanosterol: differential inhibition of sterol delta
8-isomerase and other lanosterol-converting enzymes by tamoxifen.
AB - The fact that administration of tamoxifen (Tam) to humans and laboratory animals
(e.g., rats and monkeys) results in both a drastic reduction in cholesterol and a
marked accumulation of certain sterol intermediates in their serum led us to
undertake more direct biochemical studies on the mechanism of Tam's inhibitory
action on the cholesterogenic enzymes. Of the five rat hepatic lanosterol
converting enzymes examined, the enzyme most sensitive to inhibition by Tam was
sterol delta 8-isomerase (delta 8-SI) (a 208-fold inhibition relative to
lanosterol 14 alpha-methyl demethylase), followed by sterol delta 24-reductase
(13-fold) and sterol delta 14-reductase (5.2-fold). The inhibition patterns of
all four affected enzymes were found to be noncompetitive, despite widely
different inhibition constants (Ki) of 0.21 to 23.5 microM. The inhibitory
activity of Tam on delta 8-SI was not affected by detergent-mediated
solubilization of the microsomes. In Chinese hamster ovary cells, inhibition of
delta 8-SI activity (IC50 = 0.15 microM) was paralleled by a decreased rate of
[14C]-mevalonate incorporation into cholesterol (IC50 = 0.70 microM). Our results
should provide more insight into an underlying mechanism of Tam's
cardioprotective role by interfering the operation of the pathway of cholesterol
biosynthesis from lanosterol in mammals.
PMID- 9638658
TI - Byr4, a dosage-dependent regulator of cytokinesis in S. pombe, interacts with a
possible small GTPase pathway including Spg1 and Cdc16.
AB - Coordination between karyokinesis and cytokinesis in the cell division cycle is
fundamental to a precise transmission of duplicated genome into dividing daughter
cells. byr4, a previously isolated essential gene, affects the mitotic cell cycle
and cytokinesis in S. pombe. Phenotypic analyses of the null alleles and the
overexpression of byr4 suggest that byr4 is a dosage-dependent coordinator of
karyokinesis and cytokinesis (Song et al., 1996). In this study, the functional
mechanisms of byr4 were investigated using a byr4 mutant that exhibits byr4
overexpression phenotypes in thiamine deficient media. Genetic suppression
analyses of this byr4 mutant with other cytokinesis regulatory genes in S. pombe,
cdc16, cdc7, cdc15, cdc14, and plo1, show that byr4 overexpression phenotypes are
suppressed by the overexpression of cdc16 and cdc7, but not by plo1, cdc14, and
cdc15. Also, the basal expression of byr4 and cdc7 suppresses the temperature
sensitive cdc16 mutation. However, the basal expression of either byr4 or cdc16
does not suppress the temperature-sensitive cdc7 mutation. The results of these
suppression tests suggest that byr4 genetically interacts with cdc16 and cdc7:
byr4 functions at the same level with or downstream of cdc16 and upstream of
cdc7. In the present study, we also show that Byr4 interacts with Cdc16 and Spg1
in the yeast two-hybrid assays. Recent reports suggest a possible small GTPase
pathway to regulate the timing of cytokinesis where Cdc16 functions as a GAP
(GTPase activating protein), Spg1 as a GTPase, and Cdc7 as a downstream effector.
Combined genetic and two-hybrid analyses of this study strongly suggest that Byr4
directly interacts with this possible small GTPase pathway including Cdc16, Spg1,
and Cdc7 to regulate cytokinesis in S. pombe.
PMID- 9638659
TI - Analysis of TNFB and TNFA NcoI RFLP in colorectal cancer.
AB - We examined the relationship between the NcoI RFLP of tumor necrosis factor beta
(TNFB) and alpha (TNFA) genes and the risk of colorectal cancer. The first intron
of TNFB and the -308 promoter region of TNFA NcoI RFLP were ascertained from
peripheral leucocytes of 136 colorectal cancer patients and 325 healthy controls.
The TNFB*1/TNFB*1 homozygote was significantly predominant in patients with
colorectal cancer (18.4%) compared to control subjects (9.8%) (p < 0.01), whereas
there was inverse association in TNFB*2/TNFB*2. However, the association between
colorectal cancer and TNFA genotypes was not found which indicates that these
alleles did not appear to be a susceptibility factor for colorectal cancer. TNFB
polymorphism was not associated with a clinicopathological parameter of
colorectal cancer. However, in regard to the degree of recurrence during the
postoperative survival period, TNFB*1/TNFB*1 (12.5%) and TNFB*1/TNFB*2 (24%) were
higher than TNFB*2/TNFB*2 (8.3%). Based on these results, it indicates that
TNFB*1/TNFB*1 genotypes show an increased risk for colorectal cancer, and that
the TNFB*1 allele (R.R. = 1.41) mediates some role in the initial step of
tumorigenesis or activation of dormant tumor cells, whereas TNFB*2 allele
mediates some functions associated with cytotoxicity of tumor cells.
PMID- 9638660
TI - Cerebrospinal fluid investigations for neurometabolic disorders.
AB - Careful clinical delineation and advances in analytical methods have opened new
possibilities for the detection of inherited neurometabolic disorders, some of
which require specific CSF analyses for diagnosis. Although patients suffering
from these disorders have recognizable phenotypes, there are strong indications
that remain many undiagnosed, leading to a continuation of futile diagnostic
searches and, for most disorders, withholding of available rational therapy. As
there is still widespread uncertainty about when to perform specialist CSF
investigations, it is the aim of this paper to define the place for CSF
investigations in the diagnostic work-up of a child with an encephalopathy of
unknown origin. Most neurometabolic disorders can be identified through serum,
plasma and urine analyses in conjunction with neuroradiological investigations.
Whenever CSF investigations are performed, the analysis should include
quantitative determination of lactate, pyruvate and amino acids, the latter by
methods especially suited for CSF, in addition to cells, glucose, protein,
immunoglobulin classes, specific immunoglobulins, and an evaluation of the blood
brain barrier. If the disease course is non-progressive or if extracerebral
symptoms are present in addition to an encephalopathy, e.g. endocrinological,
hepatic, muscular or renal symptoms, investigations of metabolites in CSF over
and above lactate, pyruvate and amino acids are generally noncontributary.
Specific CSF investigations, which are discussed in detail, test metabolic
pathways of brain metabolism, especially of neurotransmission. For a successful
diagnosis of these defects, analyses must be planned individually, before CSF
samples are taken, based on family history, clinical findings and disease course.
Different determinations require different logistics from taking of the sample to
shipment. One indication for specialized CSF analyses including biogenic
monoamines and GABA is severe neonatal/infantile epileptic encephalopathy. In
addition to a therapeutic trial of B6, folinic acid should be tried empirically
for two to three days as the emerging syndrome of folinic acid responsive
seizures appears to be the underlying cause in a sizable proportion of patients.
In later infancy and childhood, defects in the metabolism of the biogenic
monoamines may be suspected in patients with (fluctuating) extrapyramidal
disorders, in particular Parkinsonism dystonia or more general "athetoid cerebral
palsy", and vegetative disturbances. A severe epileptic encephalopathy and
progressive mental retardation may be present. Neuroimaging findings do not show
specific lesions. Determinations of folates and organic acids in CSF appear at
present only warrantable individually in special constellations, e.g. classical
clinical findings and disease course suggestive of glutaryl-CoA dehydrogenase
deficiency with repeated negative quantitative analyses of organic acids in
urine. The diagnosis of disorders, which require specific analyses of CSF, can
only be achieved by conscious diagnostic decisions based on a concept of the
respective disease and repeated scrupolous expert clinical evaluation aided by an
array of investigations in blood and urine as well as neuroimaging findings. No
single one investigation in CSF can serve as a "selective screening" test. A
growing awareness of these disorders is needed and should lead to increased and
earlier diagnosis of patients through fewer rather than more lumbar punctures.
PMID- 9638661
TI - SIDS, abnormal nighttime REM sleep and CNS immaturity.
AB - SIDS (Sudden Infant Death Syndrome) is the major cause of death in young,
apparently healthy, infants, yet its etiology and pathogenesis remain unknown.
SIDS peaks at 2-4 months, is more prevalent in the winter months and typically
occurs in the early morning hours when most babies are asleep, suggesting that
sleep may be part of the pathophysiological mechanism of SIDS. The sleep patterns
of infants at high risk for SIDS were analyzed to test the hypothesis that there
are abnormalities specific to nighttime sleep which may be indicative of a
central nervous system (CNS) deficit that contributes to a high frequency of SIDS
during the night. Electrophysiological sleep variables were recorded at monthly
intervals in 1-6 months-old infants during the peak age of SIDS. The risk group
(R) was resuscitated from a potentially life-threatening Sudden A-Ventilatory
Event (S.A.V.E.) and compared to a group of control infants (C) with no family
history of SIDS. The data representing four equal time intervals from 11 p.m.-11
a.m. show an abrupt, statistically significant increase in REM sleep from 2-5
a.m. in R infants. In C infants, time spent in REM sleep after 2 a.m. becomes
progressively shorter while NREM sleep is proportionately longer. From 11 p.m.-2
a.m., however, R and C infants do not differ either in the duration or in the
percent of total sleep time (TST) of REM sleep. We hypothesize that these REM
sleep abnormalities in vulnerable infants are indicative of a pervasive CNS
immaturity. The higher prevalence of SIDS in the cold winter months and in the
early morning hours, when darkness is prolonged, is discussed in relation to the
possible involvement of the circadian rhythm of melatonin.
PMID- 9638662
TI - Impaired visual perceptual performance on an object recognition task in children
with cerebral visual impairment.
AB - Visual perceptual ability and grating acuity were studied in 22 children with
cerebral visual impairment (CVI). In most studies indicating visual perceptual
impairments in CVI children, the evidence is weakened by the co-presence of
reduced nonverbal, relative to verbal, intelligence, which in itself might
account for the impaired performance on visual perceptual tasks. Our aim was to
show that CVI children's performance on a visual perceptual task is weaker than
can be expected from their nonverbal intelligence scores, thus demonstrating an
impairment that is specific to visual perception. To this end, we used an object
recognition task consisting of 60 line drawings depicting common objects in
various aberrant ways. For each drawing, the age was established at which 9 out
of 10 normal children could recognise the object depicted. This information was
used to select the subset of drawings appropriate for each of the CVI subjects'
nonverbal intelligence level, expressed as an age equivalent. Recognition
performance on this subset of drawings was impaired in 16 children (72.7%), but
was unrelated to visual acuity. We conclude that these children have a specific
visual perceptual impairment, which is not reducible to any nonverbal
intelligence impairments they might suffer.
PMID- 9638663
TI - Magnetic resonance imaging of the brain in premature infants during the neonatal
period. Normal phenomena and reflection of mild ultrasound abnormalities.
AB - An MRI study was performed in 34 preterm infants who were clinically and
neurologically normal and whose cranial ultrasound revealed no or only mild
abnormalities. The postconceptional age at MRI varied between 30.6 and 37 weeks.
The purpose of the study was to evaluate the significance of periventricular
changes in signal intensity on MRI, comparing MRI with ultrasound. T1-weighted
and T2-weighted images were assessed for changes in signal intensity of the
periventricular white matter relative to the remainder of the cerebral
hemispheric white matter. Cerebral MRIs of 13 postterm infants were additionally
investigated. In all preterm infants small localized areas of high signal
intensity on T1-weighted images and low signal intensity on T2-weighted images
were seen adjacent to the frontal horns of the lateral ventricles. They faded
with increasing age and were no longer seen one month after term in the group of
postterm infants. The areas were considered normal before term age and probably
represent remnants of the germinal matrix. Periventricular echodensities
corresponded with a zone of changed signal intensity within the periventricular
white matter on MRI. MRI signal change correlated with the presence and location
of echodensities; the MRI signal changes slowly faded away after the
echodensities disappeared.
PMID- 9638664
TI - Marinesco Sjogren syndrome with rhabdomyolysis. A new subtype of the disease.
AB - Four children from two families with characteristics of Marinesco-Sjogren
syndrome (congenital cataract, ataxia) are presented. All children had clinical
and neurophysiological signs of a demyelinating polyneuropathy. Three of them
developed acute rhabdomyolysis with marked weakness and CK levels of up to 40,000
U/I following a viral infection. In all children CK levels returned to normal
within two weeks. Symptoms were recurrent in one of the children and resulted in
a severe disability. In two other children recovery of motor function took about
a month following the first attack. Metabolic disorders of the muscle were
excluded by pathobiochemical examination of a muscle biopsy in one of the
children. In conclusion, acute rhabdomyolysis can occur as a neuromuscular
complication of Marinesco-Sjogren syndrome.
PMID- 9638665
TI - Combined therapy of medulloblastoma: review of 46 patients treated in a single
institution.
AB - Medulloblastoma is the most frequent malignant brain tumor in pediatric patients.
Early treatment strategies, combining surgery and radiotherapy alone, resulted in
survival rates of about 40% only. In the last 15 years, chemotherapy was used
more frequently in combination with surgery and radiotherapy. The rationale was
to increase the survival rate and to decrease radiation toxicity in young
children. Forty-six patients younger than 16 years were treated between July 1977
and September 1995 in our institution (32 boys and 14 girls). Thirty-nine
patients could be evaluated according to their postoperative treatment with
regard to different protocols such as SIOP 1, SIOP 2, HDMTX/VCR, HIT protocol
89/91 and Carbo-PEI (one patient). In total, 21/39 patients are alive without
evidence of disease (EFS 55 +/- 7%) with a follow-up of 26 to 210 months. Four
children are lost to follow-up. Twelve patients died after relapse, 1 child died
of MTX-induced brain atrophy, 1 patient developed a secondary malignancy (acute
lymphoblastic leukemia) and died. The best results were seen in patients treated
according to the HIT 89/91 protocol as first-line treatment (CR 9/10). The
improvement in outcome of our patients with medulloblastoma in recent years
suggests the benefit of intensified chemotherapy on survival. In addition,
refinement in surgical and radiological treatment have certainly also contributed
to the better results.
PMID- 9638666
TI - A case of myasthenia gravis in childhood associated with chronic inflammatory
demyelinating polyradiculoneuropathy.
AB - We report a 14-year-old girl who developed chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP) during the course of myasthenia gravis. Myasthenia
gravis, which was clinically of ocular type, but with waning phenomenon of the
extremities, occurred at 2 years and 4 months of age. Muscle weakness of the
lower extremities gradually developed over the next 6 years. The
electrophysiological and pathological findings fulfilled the criteria of
"possible CIDP" with severe axonal involvement. The signs of myasthenia gravis
and CIDP fluctuated synchronously. A common immunological abnormality was
suggested to underlie this rare association of myasthenia gravis and CIDP in
childhood.
PMID- 9638667
TI - An algorithm for correction of distortion in stereotaxic digital subtraction
angiography.
AB - An algorithm for correction of the geometrical distortion in digital subtraction
angiography (DSA) images was developed. Originally invented for 3D X-ray
angiography, the algorithm was implemented in a computer program designed to
fulfil the specific needs of stereotaxic DSA. The algorithm is based on
transformation of an image of a grid from a distorted image back into its
original pattern. The same transformation is then applied pixel-by-pixel to the
angiographic images, which are acquired in direct conjunction with the grid
image, without moving the gantry. The algorithm was tested in phantom studies and
in the clinical situation with seven patients in ten examinations. Comparisons
were made between co-ordinate determinations made on conventional full-size cut
film and those performed on uncorrected and corrected DSA images, using 30- and
23-cm fields of view. With our method of measurement we could not shown any
remaining geometric distortion in the corrected DSA images. This distortion
correction can, if properly applied, be used for high-precision stereotaxic DSA.
PMID- 9638668
TI - Cerebrospinal fluid flow waveforms: effect of altered cranial venous outflow. A
phase-contrast MR flow imaging study.
AB - Our purpose was to assess the effect of alterations in the cranial venous outflow
on cerebrospinal fluid (CSF) flow waveforms using phase-contrast MRI. Thirteen
healthy subjects were assessed for CSF flow and cerebral vascular flow at the C2
3 level, both before and after jugular venous compression (JVC). The flow
waveforms were assessed both as an aggregate, and after dividing subjects in two
groups based on percent jugular venous flow (PJVF) i.e. jugular outflow expressed
as percent of cerebral arterial inflow. Group 1:7 subjects with PJVF more than
and including median (predominantly jugular outflow); Group 2:6 subjects with
PJVF less than median (predominantly extra-jugular outflow). CSF waveforms: JVC
produced rounding of contours and flattening of dicrotic waves, with the effect
being greater in group 1 than group 2. In group 1, systolic upslopes of the
waveforms increased. No significant aggregate amplitude changes were noted;
amplitudes increased in group 1 (P = 0.001), and decreased in group 2 (P = 0.03).
Temporal interval to the maximum CSF systolic flow significantly increased in
group 1. Vascular flow: Arterial flow significantly decreased in group 1. Jugular
flow significantly decreased in both groups. The results suggest that CSF flow
waveforms are sensitive to alterations in the cranial venous outflow. Changes in
group 1 are most likely because of an elevation in intracranial pressure.
Analysis of CSF flow waveforms appears a promising noninvasive tool for
assessment of cranial compartment.
PMID- 9638669
TI - Optimisation of unenhanced MRI for detection of lesions in multiple sclerosis: a
comparison of five pulse sequences with variable slice thickness.
AB - We used five MRI sequences in six patients with multiple sclerosis (MS):
conventional spin-echo (CSE) with 5-mm slices; 2D fast spin-echo (FSE) with 2-mm
slices; multishot T2*-weighted echo-planar imaging (EPI) with 5-mm slices; fast
fluid-attenuated inversion recovery (fFLAIR) with 2-mm slices; and 3D fast spin
echo with 1.5-mm-thick slices. A total of 225 lesions were detected on CSE, 274
on 2D FSE, 137 on EPI, 385 on fFLAIR and 320 on 3D FSE. The EPI sequence was
clearly the least sensitive and susceptibility artefact was a problem,
particularly in the brain stem and temporal lobes. Fast FLAIR displayed a much
higher number of supratentorial lesions (380) than 3D FSE (297), 2D FSE (264) or
CSE (211). However, in the posterior cranial fossa 3D FSE was the most sensitive
sequence (23 lesions), followed by CSE (14) and 2D FSE (10), while fFLAIR (5) was
extremely insensitive.
PMID- 9638670
TI - Subcortical frontal lesions on MRI in patients with motor neurone disease.
AB - MRI was performed in 32 patients with motor neurone disease (26 men and 6 women,
aged 40-77 years) and in a control group of 21 subjects. Of the patients studied,
19 had definite and 11 probable amyotrophic lateral sclerosis (ALS) and two had
progressive bulbar palsy. In 10 patients there were asymmetrical bilateral foci
of increased signal intensity on proton-density and T2-weighted images, confined
to the white matter. Two patients had only cortical frontal atrophy and slightly
increased ventricular size, whereas 20 had normal MRI. The focal lesions were not
confined to corticospinal tracts, but were also observed in subcortical frontal
areas. While the lesions along the corticospinal tracts correspond to pyramidal
tract degeneration, the subcortical foci correlate with degeneration of the
frontal bundles and indicate generalised involvement of the central nervous
system.
PMID- 9638671
TI - MRI features of choroid plexitis.
AB - Four cases of choroid plexitis of the brain (two with cryptococcosis and two with
tuberculosis) are presented. The four patients showed either unilateral
enlargement (3) or bilateral enlargement (1) and dense enhancement of the choroid
plexus in the lateral ventricles (4) and fourth ventricle (1) in association with
clinical findings of leptomeningitis. All patients had unilateral cystic
dilatation of the temporal horn of the lateral ventricle presumably secondary to
entrapment of the temporal horn and extensive oedema around the ipsilateral
ventricle.
PMID- 9638672
TI - Amyloid angiopathy causing widespread miliary haemorrhages within the brain
evident on MRI.
AB - The case of a 70-year-old woman with cerebral amyloid angiopathy (CAA) is
presented. MRI of the head showed widespread miliary foci of haemorrhage within
the cerebrum and cerebellum, with some additional linear lesions within the
cerebral cortex and patchy lesions in the white matter. This is in contrast to
the more usual pattern of intracranial haemorrhage in CAA, i.e., a lobar
haematoma.
PMID- 9638673
TI - Secondary superficial siderosis of the central nervous system in a patient
presenting with sensorineural hearing loss.
AB - We present a 50-year-old man who was investigated for sensorineural hearing loss.
On MRI of the brain superficial siderosis of the central nervous system was seen,
while MRI of the spine revealed an ependymoma of the cauda equina. This case
illustrates the importance of performing T2-weighted imaging of the brain and
posterior fossa when sensorineural hearing loss is present. Spine imaging is
mandatory when superficial siderosis of the brain is diagnosed without
identification of a bleeding source in the brain.
PMID- 9638674
TI - 1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative
analysis.
AB - Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male
and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17
patients with normal MRI of the basal ganglia without metabolic disturbance
(control group) and 11 patients with various metabolic diseases: one case each of
high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh
disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic
syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic
acidemia with abnormal MRI of the basal ganglia or blood or urine analysis
(abnormal group). The MR spectrum was measured by using STEAM. The MR-visible
water content of the region of interest was obtained. Levels of myoinositol,
choline, creatine and N-acetylaspartate were measured using a semiquantitative
approach, with absolute reference calibration. In the control group, there was a
gradual drop of water content over the first year of life; N-acetylaspartate,
creatine and myoinositol levels showed no significant change with age, in
contrast to the occipital, parietal and cerebellar regions. Choline showed a
gradual decrease for the first 2 years of life and then remained fairly constant.
In the abnormal group the water content was not significantly different. N
Acetylaspartate was decreased in patients with high serum sodium and high serum
osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic
acidemia. Decreased creatine was also found in Leigh disease, and decreased
choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated
in the patient with abnormally high serum sodium, and decreased in the hemolytic
uremic syndrome.
PMID- 9638675
TI - Cerebellar arteriovenous malformations in children.
AB - We review the presentation, imaging findings and outcome in 18 children with
cerebellar arteriovenous malformations (AVM). This group is of particular
interest because of the reported poor outcome despite modern imaging and
neurosurgical techniques. All children had CT and 15 underwent catheter
angiography at presentation. Several of the children in the latter part of the
study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing
intracranial haemorrhage. The remaining child presented with temporal lobe
epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM.
This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children
had pre-existing abnormalities of possible relevance. One had a vascular
malformation of the cheek and mandible, one a documented chromosomal abnormality
and another a midline cleft upper lip and palate. Six of the 17 children with a
ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other
than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who
had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous
outflow obstruction (one child having both an aneurysm and obstruction). The
severity of clinical presentation was directly related to the size of the acute
haematoma, which was a reasonable predictor of outcome.
PMID- 9638676
TI - CT and MRI of microcephalia vera.
AB - CT and MRI findings in three patients, two of them siblings, with microcephalia
vera are presented. In this rare entity, a very small brain with an extremely
thin, smooth cortex and increase surrounding cerebrospinal fluid are observed.
PMID- 9638677
TI - Imaging of huge lingual thyroid gland with goitre.
AB - We present the CT and MRI findings in a 75-year-old woman with a huge
pathologically proven lingual thyroid which underwent goitrous degeneration. CT
and MRI showed a midline, tongue-based, exophytic mass with areas of necrosis and
heterogeneous contrast enhancement, as seen in large goitres in the normal
thyroid gland.
PMID- 9638678
TI - Transmural migration of an intracavernous carotid detachable balloon used to
control surgically induced haemorrhage.
AB - We report a case in which a balloon detached in the carotid siphon for control of
iatrogenic bleeding migrated to the oesophagus. We discuss the pathophysiology.
PMID- 9638679
TI - Transplacental cocaine exposure. 1: A rodent model.
AB - To characterize the transplacental effects of cocaine on the developing brain, we
have developed a mouse model of gestational cocaine exposure. Pharmacokinetic
analysis revealed that cocaine and its metabolites (BE, BNE, and NC) were found
in fetal brain and plasma at 30 and 120 min following SC administration to
embryonic day (E) 17 pregnant Swiss Webster mice. Pregnant dams injected twice
daily with cocaine HCl at 20 mg/kg SC from gestational day E8 to E17 (COC)
demonstrated less food intake and lower percentage weight gain than vehicle
injected dams allowed access to food ad lib (SAL). A nutritionally paired control
group of dams injected with saline vehicle and pair-fed with the COC dams (SPF)
demonstrated the lowest percentage weight gain of all three groups. The surrogate
fostered offspring of COC and SPF dams demonstrated persistent growth retardation
[on postnatal days (P) 1, P9, and P50] and transient brain growth retardation (on
P1 and P9) when compared to pups born to SAL dams. We conducted behavioral tests
that allowed us to dissociate the indirect effect of cocaine-induced malnutrition
from a direct effect of prenatal cocaine administration in altering postnatal
behavior. Pups from all three groups were tested for first-order Pavlovian
conditioning on P9 or P12, or for the ability to ignore redundant information in
a blocking paradigm on P50 or P100. Unlike the SPF and SAL controls, COC mice
(i.e., mice born to COC dams) were unable to acquire an aversion to an odor
previously paired with shock on P9. This learning deficit was transient because
on P12, COC mice trained on the same conditioning task displayed an aversion to
the odor that was indistinguishable from the SPF and SAL controls. P50 and P100
COC mice (and to a lesser extent, SPF mice) demonstrated a persistent behavioral
deficit in the blocking paradigm, which may reflect alterations in selective
attention. We discuss how these findings in our rodent model have developmental
implications for human infants exposed to cocaine in utero.
PMID- 9638680
TI - Transplacental cocaine exposure. 2: Effects of cocaine dose and gestational
timing.
AB - We have utilized a mouse model of transplacental cocaine exposure to investigate
the effects of cocaine dose and gestational timing in altering brain and body
growth and postnatal behavior in exposed offspring. Pregnant dams were injected
with cocaine HCl at 40 mg/kg/day (COC 40) or 20 mg/kg/day (COC 20), or 10
mg/kg/day (COC 10) SC from embryonic day (E) 8 to E17, or cocaine HCl at 40
mg/kg/day SC from E8 to E13 (COC Early) or from E13 to E17 (COC Late) divided in
two daily doses. COC 40 and COC Late dams, as well as dams in nutritionally
paired control groups (injected with saline vehicle and pair-fed with the COC
dams: SPF 40, SPF 20, SPF 10), demonstrated less weight gain than SAL controls
(injected with saline vehicle and allowed access to food ad lib). The surrogate
fostered offspring of COC 40 and SPF 40 dams demonstrated brain and body growth
retardation [on postnatal day (P) 1 and P9] when compared to pups born to SAL
dams. Offspring of COC Late, SPF 20, and SPF 10 dams demonstrated brain and body
growth retardation on P1 when compared to pups born to SAL dams. Pups from all
groups were tested for first-order Pavlovian conditioning on P9, or for the
ability to ignore redundant information in a blocking paradigm on P50. Only COC
40 mice (i.e., offspring born to COC 40 dams) were unable to acquire an aversion
to an odor previously paired with shock on P9. When compared with SAL controls,
COC 40 mice (and to a less significant extent SPF 40 mice) demonstrated a
persistent behavioral deficit in the blocking paradigm on P50, which may reflect
alterations in selective attention. Correlation analyses indicated that the dose
and gestational timing of transplacental cocaine exposure, and varying degrees of
malnutrition, had effects on blocking performance, with greater prenatal cocaine
exposure and increased prenatal malnutrition resulting in more significant
behavioral impairments. A path regression analysis demonstrated independent and
significant effects of prenatal cocaine as well as prenatal malnutrition in
contributing to impaired performance in the blocking paradigm. As suggested by
the clinical literature, our preclinical data support a model whereby the dose
and duration of prenatal cocaine exposure have direct effects on offspring brain
and body growth and on behavioral performance.
PMID- 9638681
TI - Transplacental cocaine exposure. 3: Mechanisms underlying altered brain
development.
AB - In a mouse model of transplacental cocaine exposure we have demonstrated
alterations in brain structure and function of offspring including disturbances
of brain growth, disruption of neocortical cytoarchitecture, and transient as
well as persistent behavioral deficits. One mechanism by which cocaine may alter
fetal brain development is through cocaine-induced alpha-adrenergic-mediated
(uterine) arterial vasoconstriction. In this study pregnant Swiss Webster (SW)
mice were injected with cocaine HCl (20 or 40 mg/kg, SC) without any changes
evident in mean arterial blood pressure (MAP) measurements. These physiology
results suggest that in our mouse model, cocaine's transplacental effects on the
fetus are not due to cocaine-induced maternal vasoconstriction, nor concomitant
hypoperfusion of the fetus. In a separate series of experiments, pregnant SW dams
were administered cocaine HCl at 40 mg/kg/day (COC 40), 20 mg/kg/day (COC 20), or
10 mg/kg/day (COC 10) [SC, divided in two daily doses, from embryonic day (E) 8
to E17 inclusive]. Additional groups of cocaine-treated dams were administered
phentolamine (5 mg/kg, SC), a short-acting alpha-adrenergic antagonist, 15 min
prior to each cocaine dose (Phent COC 40, Phent COC 20, Phent COC 10). Animals
born to Phent COC 40 dams demonstrated transient postnatal brain growth
retardation and behavioral deficits in first-order conditioning of P9 mice
comparable to mice born to COC 40 dams, which received the same regimen of
cocaine injections without phentolamine pretreatment. Like COC 40 offspring,
Phent COC 40 offspring also demonstrated a persistent deficit in the blocking
paradigm. The behavioral and growth findings confirm and extend the physiology
data, and imply that in our rodent model, alpha-adrenergic mechanisms (including
maternal vasoconstriction) are unlikely to mediate these toxic effects of
transplacental cocaine exposure on developing brain.
PMID- 9638682
TI - Neurobehavioral and pregnancy effects of prenatal zidovudine exposure in Sprague
Dawley rats: preliminary findings.
AB - In 1994, the Public Health Service made prenatal zidovudine (ZDV, AZT) the
standard of care to prevent mother-to-child transmission of HIV. The current
study was undertaken to determine if prenatal exposure to ZDV has an impact on
pregnancy outcomes, birth anomalies, or offspring behavior in an animal model
using Sprague-Dawley (SD) rats. Thirty-one virgin female SD rats were mated and
randomly assigned to receive either ZDV at 150 mg/kg/day or vehicle via gastric
intubation for 22 days starting on gestation day (G) 1. On G 22, teratologic
examination of 12 litters showed no gross structural malformations. There were no
significant differences between the groups for maternal food and water
consumption or maternal weight gain across pregnancy. However, ZDV treatment
significantly reduced litter size and increased birth weights for both male and
female pups. One developmental milestone, pinna detachment, occurred
significantly earlier in the ZDV-exposed male pups compared to the vehicle
intubated male controls. On day 21-22 of life, pups in each litter were injected
with one of four doses of amphetamine and were observed for behavioral activity
in a photobeam-based activity monitor for 1 h. Overall amphetamine increased
activity and decreased thigmotaxis or wall-hugging behavior. ZDV treatment
increased the locomotor response to amphetamine in females only and dampened the
action of amphetamine to decrease thigmotaxis in both genders. Further studies
are warranted to determine the threshold dose at which these changes occur, the
duration of the effects, as well as the neurochemical system(s) responsible for
the altered amphetamine responses.
PMID- 9638683
TI - Neurobehavioral changes in shoe manufacturing workers.
AB - A study was carried out to evaluate: (a) the value of a cumulative exposure
estimate (CEE) calculated from limited information on air concentration; and (b)
whether chronic exposure to mixed organic solvents at a shoe manufacturing
factory has induced neurobehavioral changes. The Neurobehavioral Core Test
Battery was administered to 40 female workers from a shoe manufacturing factory
and 28 housekeepers as referents. The airborne concentrations of the solvents as
a mixture were 0.46-0.71 at the frame making process and 1.83-2.39 at the
adhesive process. Performance was analyzed by three exposure indices: current
department, exposure duration, and CEE. The Santa Ana Dexterity test showed
statistically significant differences only in CEE. In particular, the group with
higher exposures had a significantly poorer performance than the reference group,
on preferred hand trials. The results suggested that CEE appeared to be a better
indicator of mixed organic solvents exposure, and neurobehavioral changes were
associated with CEE over 10 years.
PMID- 9638684
TI - CYP2D1 polymorphism in methamphetamine-treated rats: genetic differences in
neonatal mortality and effects on spatial learning and acoustic startle.
AB - d-Methamphetamine (MA) is one of more than two dozen drugs included in the
cytochrome P450-mediated "debrisoquine oxidation polymorphism" panel. The human
gene (CYP2D6) is responsible for the "poor metabolizer" (PM) and "extensive
metabolizer" (EM) phenotypes for drugs such as MA; a similar polymorphism (the
CYP2D1 gene) exists in rats. Female Black or Dark Agouti rats exhibit the PM
phenotype, whereas Sprague-Dawley (SD) rats show the EM trait. We sought to test
the possibility that these strains of rats might exhibit altered MA-induced
developmental neurotoxicity. Neonatal exposure to MA on days 11-20 has previously
been shown to induce spatial learning deficits in Sprague-Dawley rats when tested
as adults. Therefore, in the present experiment, on postpartum days 11 through
20, ACI (Black Agouti) and SD progeny were administered 30 mg/kg MA twice daily.
MA treatment caused larger increases in mortality in ACI than in SD rats,
suggesting that decreased MA metabolism leads to enhanced toxicity and lethality.
Female offspring were assessed behaviorally as adults. No differences were
observed in acoustic startle or straight swimming channel performance. In the
Morris maze, both MA-treated rat strains showed longer latencies to find the
hidden platform during acquisition, reinstatement, and shift trials, and spent
less time in the target quadrant on probe trials; no strain differences in
learning were found. Although these data do not support our hypothesis that MA
induced developmental neurotoxicity might be enhanced in the ACI rat, this
interpretation is tempered by the high mortality rate (65%) of MA-treated ACI
neonates, suggesting a possible "survivor effect" in this strain.
PMID- 9638685
TI - Lack of effect of methylmercury exposure from birth to adulthood on information
processing speed in the monkey.
AB - Although it is established that developmental methylmercury exposure produces
severe motor and sensory impairment, the effect on cognitive function is less
clear. To explore this issue, monkeys with robust methylmercury-induced deficits
in visual, auditory, and somatosensory function were tested on a series of tasks
assessing central processing speed, which is highly correlated with intelligence
in humans. Five monkeys (Macaca fascicularis) were dosed from birth to 7 years of
age with 50 micrograms/kg/day of mercury as methylmercuric chloride. Blood
mercury levels were stable at 0.8-1.1 micrograms/g until cessation of dosing.
When they were 20 years old, these monkeys and four age- and rearing-matched
controls were tested on a series of simple and complex reaction time tasks. The
monkey sat in a primate chair with a stainless steel bar centered at waist
height. Four push buttons equidistant from the steel bar were mounted on a
vertical Plexiglas panel in front of the monkey. The monkey was required to make
contact with the bar, then release the bar and push the appropriate button in
response to a change in stimulus conditions. For the first task (simple reaction
time), the monkey was required to respond on a button when it changed from unlit
to red. The monkey then performed a sequence of complex reaction time tasks: two
button, four-button, and several tasks of increasing complexity using four
buttons and multiple colors. For each task, the latency to release the bar after
the stimulus change (central processing speed) and to move the hand from the bar
to the button (motor speed) were determined. Lastly, the monkey was required to
make the quickest possible motor response on the simple reaction time task. There
were no differences between groups on any aspect of the experiment. These data
provide further evidence for absence of cognitive impairment in monkeys exposed
developmentally to methylmercury.
PMID- 9638686
TI - Binge neonatal alcohol intubations induce dose-dependent loss of Purkinje cells.
AB - Previous work using artificial rearing methods to administer alcohol to neonatal
rats identified postnatal days (PD) 4-6 as a period of enhanced vulnerability to
alcohol-induced Purkinje cell loss. To develop an alternative to artificial
rearing, alcohol was administered to pups in a binge pattern of exposure using
acute intubations, and dose-related effects on blood alcohol concentrations
(BACs), somatic growth, and cerebellar Purkinje cell survival were assessed. Pups
were intubated with alcohol in milk formula, twice a day, 2 h apart, with total
daily doses of 4.5, 5.25, or 6.0 g/kg of alcohol. After intubations on PD 4, the
blood alcohol concentration (BAC)-time curves systematically increased with
increasing dose. Intubation of these doses on PD 4-6 produced significant, dose
dependent reductions in the total number of cerebellar Purkinje cells on PD 10,
counted using the stereological optical fractionator. Somatic growth was
significantly affected only by the highest dose. These dose manipulations using
intubations confirmed that Purkinje cell death systematically increased as a
function of BAC profiles within the PD 4-6 window of vulnerability.
PMID- 9638687
TI - Differential effects on cognitive functioning in 9- to 12-year olds prenatally
exposed to cigarettes and marihuana.
AB - Cognitive performance was examined in 131 9-12-year-old children for whom
prenatal marihuana and cigarette exposure had been ascertained. The subjects,
participants in an ongoing longitudinal study, were from a low-risk,
predominantly middle class sample. The tasks included the WISC-III and a series
of tests assessing aspects of cognition subsumed under the rubric of executive
function. Consistent with results obtained at earlier ages, discriminant function
analysis revealed a dose-dependent association, which remained after controlling
for potential confounds (including secondhand smoke), between prenatal cigarette
exposure and lower global intelligence scores with the verbal subtests of the
WISC maximally discriminating among levels of in utero exposure. In contrast,
prenatal marihuana exposure was not associated with global intelligence or the
verbal subtests. Rather, this drug was negatively associated with the executive
function tasks that require impulse control and visual analysis/hypothesis
testing and with a number of WISC subtests requiring the same abilities. The
interpretation of these results is discussed in terms of executive function and
is related to earlier observations of this sample and to the extant prefrontal
and general marihuana literature.
PMID- 9638688
TI - Long-term changes in rat social behavior following treatment with
trimethylolpropane.
AB - A potent convulsant, trimethylolpropane phosphate (TMPP), was evaluated for long
term effects on measures of social behaviors and anxiety in Long-Evans rats.
Animals received three to four daily treatments of TMPP (0.1 mg/kg/ml) beginning
at age 23 days in Experiment 1 and 73 days in Experiment 2. Gregariousness was
measured in juvenile play and adult social investigation. Anxiousness was
measured in the open field and elevated plus-maze. Long-lasting changes in social
behaviors were found: play and social investigation were elevated, especially in
female rats. Also, an aversive environmental experience associated with TMPP
treatment influenced the drug effect on social investigation for males, but not
females. In males, TMPP- vs. VEH-treated animals displayed greater social
investigation when the treatment was in a positive environment than in an
aversive one. In contrast, TMPP- vs. VEH-treated females showed greater social
investigation regardless of environmental experience. There were no treatment
group differences for measures of anxiety. These results suggest short-term
exposure to TMPP may lead to long-lasting changes in specific social behaviors
and neural substrates related to them, but not to changes in anxiousness.
PMID- 9638689
TI - Active oxygen species formation in synaptosomes exposed to an aluminum chelator.
AB - This study evaluates the potential of two chelators, 1,2-dimethyl-3
hydroxypyridine-4-one (Hdpp) and 1-n-butyl-2-methyl-3-hydroxypyridin-4-one
(Hnbp), to modulate cerebral rates of free radical production. The fluorometric
assay for 2',7'-dichlorofluorescein, which is formed by oxidation of a
nonfluorescent precursor (2',7'-dichlorofluorescein diacetate), was used to assay
reactive oxygen species (ROS) production. The chelator Hdpp alone and the
aluminum complexes of each chelator, Al (dpp)3 and Al (nbp)3, all inhibited basal
rates of generation of ROS within a rat cerebral synaptosomal fraction. In the
presence of an iron salt (1 microM FeSO4), a major enhancement of synaptosomal
ROS formation was apparent. However, with the addition of an equimolar
concentration of Hdpp, Al(dpp)3, or Al(nbp)3, this stimulation was completely
abolished. The N-substituted-3-hydroxy-4-pyridinones have been proposed to be of
clinical utility for the removal of iron or aluminum from tissues. The clinical
potential of this class of chelator may be enhanced by their ability to inhibit
iron-related oxidative events.
PMID- 9638690
TI - Combined effects of simultaneous exposure to toluene and ethanol on auditory
function in rats.
AB - Three experimental groups and one control group of Long-Evans rats were used to
study the combined effects of toluene and ethanol on auditory function. The first
experimental group was exposed to toluene vapors (1750 ppm, 6 h/day, 5 days/week,
4 weeks), the second one was daily gavaged with a saline solution of ethanol (4
g/kg, 4 weeks), and the last group was simultaneously exposed to both toluene and
ethanol. Auditory function was tested by recording brain stem (inferior
colliculus) auditory-evoked potentials for audiometric frequencies ranging from 2
to 32 kHz. Urinary hippuric acid was dosed to check the toluene metabolism during
the experiments. Ethanol clearly modified the toluene metabolism in the present
experimental conditions. As a result, the hearing loss induced by a simultaneous
exposure to both ethanol and toluene was larger than that induced by exposure to
toluene alone.
PMID- 9638691
TI - The lost generation.
PMID- 9638692
TI - Atypical odontalgia.
PMID- 9638693
TI - Cavernous hemangioma of the masseter muscle.
PMID- 9638694
TI - Alloplastic temporomandibular joint reconstruction.
PMID- 9638695
TI - Platelet-rich plasma: Growth factor enhancement for bone grafts.
AB - Platelet-rich plasma is an autologous source of platelet-derived growth factor
and transforming growth factor beta that is obtained by sequestering and
concentrating platelets by gradient density centrifugation. This technique
produced a concentration of human platelets of 338% and identified platelet
derived growth factor and transforming growth factor beta within them. Monoclonal
antibody assessment of cancellous cellular marrow grafts demonstrated cells that
were capable of responding to the growth factors by bearing cell membrane
receptors. The additional amounts of these growth factors obtained by adding
platelet-rich plasma to grafts evidenced a radiographic maturation rate 1.62 to
2.16 times that of grafts without platelet-rich plasma. As assessed by
histomorphometry, there was also a greater bone density in grafts in which
platelet-rich plasma was added (74.0% +/- 11%) than in grafts in which platelet
rich plasma was not added (55.1% +/- 8%; p = 0.005).
PMID- 9638696
TI - The validity of clinical examination for diagnosing anterior disk displacement
with reduction.
AB - OBJECTIVE: The objective of this study was to evaluate the diagnostic accuracy of
a clinical examination for diagnosing anterior disk displacement with reduction.
STUDY DESIGN: A series of 273 consecutive patients with temporomandibular
disorders were clinically examined according to well-defined criteria. The
patients were examined for clicking by digital palpation during maximal mouth
opening and closing (the Clicking test). When clicking was identified, two
additional tests were performed: one determined whether the clicking was
eliminated at a protruded position, and the other determined whether the clicking
became louder when the patient's mandible was manipulated toward the eminences.
Bilateral magnetic resonance images were subsequently obtained from all patients;
the clinical examination findings were then compared to the imaging-based
diagnoses of the temporomandibular joint status to assess the diagnostic accuracy
of the clinical findings. RESULTS: Although the predictability of identifying
anterior disk displacement with reduction by clicking was relatively low, it
increased to an acceptable level when the additional tests were used. The overall
accuracy for the Clicking test combined with either of the other tests was about
90%. CONCLUSION: Our results suggest that anterior disk displacement with
reduction can be diagnosed with considerable accuracy through the use of a
clinical examination only.
PMID- 9638697
TI - The validity of clinical examination for diagnosing anterior disk displacement
without reduction.
AB - OBJECTIVE: The objective of this study was to evaluate the diagnostic accuracy of
patient history and clinical signs as confirmed by magnetic resonance imaging
examination for diagnosing anterior disk displacement without reduction. STUDY
DESIGN: A series of 273 consecutive patients with temporomandibular disorders
were clinically examined according to well-defined criteria. Patients were first
asked if they had a history of clicking. The following clinical characteristics
of anterior disk displacement without reduction were then assessed: (1) maximal
mouth opening less than 40 mm; (2) deflection of the mandible to the affected
side at the maximal mouth opening position; (3) limitation of condylar
translation on palpation during maximal mouth opening; (4) preauricular pain
during mandibular movements; and (5) crepitation. Bilateral magnetic resonance
images were obtained for all patients, and the magnetic resonance imaging
interpretation was compared with the clinical examination findings to assess the
diagnostic accuracy of the clinical findings. RESULTS: The sensitivity was
considerably low in contrast with the relatively high specificity for all six
clinical parameters tested. The overall accuracies of the clinical parameters
ranged from 71% to 81%. CONCLUSION: Our results suggest that the predictability
of historical or clinical findings to differentiate anterior disk displacement
without reduction from other diagnoses is not high.
PMID- 9638698
TI - Design and preliminary evaluation of an extraoral Gow-Gates guiding device.
AB - Incidence of unsuccessful anesthesia with the Gow-Gates mandibular block may be
greater than that for the inferior alveolar nerve block until the administrator
gains experience with this technique. The aim of this study was to develop a
support instrument for the Gow-Gates mandibular block in an attempt to make the
described procedure easier and more precise, especially for beginners. In a
preliminary clinical experiment 40 patients were anesthetized with this new
device; a control group of 40 patients was anesthetized without the instrument.
The operators were 80 dental students without previous clinical experience in the
Gow-Gates technique. In the experimental group 39 (97.5%) of the 40 patients were
provided with complete anesthesia. In the control group 31 (77.5%) of the 40
patients were completely anesthetized. It appears that the new device allows a
great level of success with the Gow-Gates mandibular block, irrespective of the
clinical experience of the operator.
PMID- 9638699
TI - Effect of impact and injury characteristics on post-motor vehicle accident
temporomandibular disorders.
AB - OBJECTIVES: The objective of this study was to assess the potential effects of
motor vehicle accident impact and injury characteristics on post-motor vehicle
accident temporomandibular disorders in terms of presenting signs and symptoms,
diagnoses, treatment regimens, and outcomes. STUDY DESIGN: A retrospective chart
review of 50 patients with post-motor vehicle accident temporomandibular
disorders from a private oral medicine practice was undertaken. Various
demographic data and data related to temporomandibular disorders and motor
vehicle accident impact and injury characteristics were collected. Chi-square and
Fisher exact tests and multiple regression analyses were performed. RESULTS:
Patients involved in front-end collisions or motor vehicle accidents resulting in
severe vehicle damage reported more direct orofacial injury. However, those in
rear-end collisions or accidents resulting in minimal vehicle damage required
more treatment. Direct head or orofacial injury was therefore not a prognostic
indicator. From multiple regression analyses, indicators of a poorer prognosis
were minimal vehicle damage, lack of headrest use, driver position, and
settlement of insurance claim. CONCLUSIONS: In this patients group several
prognostic indicators for patients with post-motor vehicle accident
temporomandibular disorders were identified; these indicators may influence the
management approach for this patient population.
PMID- 9638700
TI - Effect of muscle relaxation splint therapy on the electromyographic activities of
masseter and anterior temporalis muscles.
AB - The purpose of this study was to compare the effectiveness of splint therapy on
the electromyographic activity of masticatory muscles (anterior temporalis and
masseter) before and after the application of a muscle relaxation splint.
Electromyography recordings from the masseter and anterior temporalis muscles
were analyzed quantitatively during maximal biting in the intercuspal position
both before and after treatment without a splint. Fourteen patients whose chief
complaint was masticatory muscle pain were selected for the study. After the
initial evaluations muscle relaxation splints were applied, and the patients were
instructed to use the splints for 6 weeks. Surface electromyographic recordings
were taken from each patient before the beginning of clinical therapy and after 6
weeks of wearing the splints. The data obtained were analyzed through paired
sample t tests and Wilcoxon's signed rank tests. The results of the study were as
follows: (1) the electromyographic activity of the two muscles during maximal
biting was not markedly changed after the muscle relaxation splint was used; and
(2) the changes observed in electromyographic activity of the involved and
noninvolved sides were insignificant as well.
PMID- 9638701
TI - Caries in patients with non-insulin-dependent diabetes mellitus.
AB - OBJECTIVE: The purpose of this study was to investigate the prevalence and risk
factors of dental caries in patients with non-insulin-dependent diabetes mellitus
and to determine whether these factors are associated with metabolic control and
vascular complications of the disease. STUDY DESIGN: Both the occurrence of
caries, acidogenic oral bacteria, and yeasts and salivary flow were studied in 25
patients with non-insulin-dependent diabetes mellitus whose diagnosis had been
set 13 to 14 years earlier and in whom the metabolic evolution of the disease was
well established. The patients' glycemic control was determined by means of
analysis of the blood hemoglobin A1C concentration at the time of dental
examination. The control group consisted of 40 nondiabetic subjects in the same
age group. Decayed, missing, and filled teeth indices and numbers of surfaces
with caries, filled surfaces, and root caries were determined by means of
clinical dental caries examination. Stimulated salivary flow was measured, and
levels of Streptococcus mutans, lactobacilli, and yeasts were analyzed. RESULTS:
The median hemoglobin A1C concentration of the patients was 8.6%, which indicates
poor metabolic control of diabetes. No association was found between the
metabolic control of disease and dental caries. The occurrence of dental caries
was not increased in the patients with non-insulin-dependent diabetes mellitus in
comparison with the control subjects. The counts of acidogenic microbes and
yeasts did not differ statistically significantly between the groups. There was
no association of caries with the prevalence of coronary artery disease or
hypertension in either the patients or the control subjects. In a stepwise
logistic regression model, a salivary flow of at least 0.8 ml/min was related to
the occurrence of dental caries in patients with non-insulin-dependent diabetes
mellitus, whereas negligence with respect to dental care was the most important
risk predictor in the control group. CONCLUSION: Our results showed no effect of
diabetes on the prevalence of caries. However, the caries-protective effect of
saliva was partly lost in patients with non-insulin-dependent diabetes mellitus.
PMID- 9638702
TI - Penetration of human vaginal and buccal mucosa by 4.4-kd and 12-kd fluorescein
isothiocyanate-labeled dextrans.
AB - In a previous study we demonstrated that human vaginal mucosa was as permeable to
water as was buccal mucosa. Water, however, is a very small molecule with a
molecular weight of 18 d. To further explore similarities between these two types
of mucosa with respect to permeability, it was decided to investigate the passage
of two large, hydrophilic molecules across these epithelia. Specimens of fresh,
clinically healthy human vaginal and buccal mucosa were taken from excised tissue
obtained during vaginal hysterectomies and various oral surgical procedures.
Seven biopsy materials from each specimen were mounted in flow-through diffusion
cells (exposed area, 0.039 cm2), and their permeability to 4.4- and 12-kd
fluorescein-isothiocyanate-labeled dextrans was determined through use of a
continuous flow-through perfusion system. Dextran was detected by means of a
fluorospectrophotometric method at excitation and emission wave lengths of 498
and 520 nm, respectively. Specimens were examined histologically before and after
permeability experiments, and similarities between vaginal and buccal tissues
were verified. No statistically significant differences between the flux values
of the 4.4-kd dextran across vaginal and buccal mucosa were found. However, for
the 12-kd dextran the flux rate across buccal mucosa was significantly higher
than the rate across vaginal mucosa. These results demonstrate that human vaginal
mucosa is for practical purposes as permeable as buccal mucosa to 4.4-kd
hydrophilic molecules. This further supports the hypothesis that vaginal mucosa
may be a useful model for studying the passage across buccal mucosa of chemical
compounds and therapeutic agents that are less than approximately 4.4 kd in
molecular mass. For a 12-kd dextran the flux rate across buccal mucosa is
significantly higher than the flux rate across vaginal mucosa, and the model
becomes inaccurate.
PMID- 9638703
TI - Immunohistochemical evaluation of bcl-2 oncoprotein in oral dysplasia and
carcinoma.
AB - The proto-oncogene bcl-2 is associated with follicular lymphoma involving
translocation t(14;18)(q32;q21) and is also overexpressed in various neoplasms.
We report deregulation of bcl-2 expression during progression from oral
epithelial dysplasia to squamous cell carcinoma. Immunohistochemical analysis
with monoclonal antibodies to bcl-2 oncoprotein in formalin-fixed paraffin
embedded tissue sections revealed that severe epithelial dysplasias had a higher
percentage of immunoreactivity than did mild and moderate dysplasias and squamous
cell carcinomas. Expression of this oncoprotein was directly proportional to the
degree of epithelial dysplasia, and nondysplastic basal cells contiguous to
neoplastic lesions also expressed bcl-2. These findings, along with down
regulation of bcl-2 in differentiating carcinomas, suggest a role for this
oncoprotein in relatively early stages of oral tumor progression. Differentiating
neoplastic cells with marginal or no bcl-2 reactivity showed heterogeneous cell
labeling of varying intensity for differentiation-associated cytokeratin (CK13),
indicating their inverse topographic relationship.
PMID- 9638704
TI - Cell population changes during atrophy and regeneration of rat parotid gland.
AB - Limited data exist regarding the changes in number and location of myoepithelial
cells during salivary gland atrophy and regeneration. Through the use of double
immunohistochemical labeling for muscle-specific actin and amylase coupled with
morphometric analysis, this study investigated the changes in distribution and
proportion of cell types during salivary gland atrophy/regeneration phases in a
model previously used to study proliferation in rat parotid gland. The double
immunohistochemical labeling clearly showed the changes in proportion of cell
types in the atrophying and regenerating glands. The morphometric analysis showed
that the relative myoepithelial area increased (as did the intercalated duct and
striated duct areas) as the gland atrophied. Myoepithelial cells occupied 19.0%
of the total epithelial area by day 7 of atrophy, up from 2.7% in the resting
gland. Regeneration of acinar cells was obvious 1 day after duct release. The
myoepithelial cell area decreased to 4.3% of the total epithelial area by day 14
of regeneration; this value was higher than the percentage of area in the resting
gland (p = 0.02). The relative areas of acinar, striated duct, and intercalated
duct cells returned to resting levels after 14 days of regeneration. The
morphometric and histologic results of this study show that the parotid gland is
capable of regenerating to essentially normal anatomic condition after 7 days of
gland atrophy and then 14 days of regeneration. Each type of cell, however,
responded to the atrophy and regeneration differently. Atrophy of salivary glands
from radiation therapy. Sjogren's syndrome, or sialadenitis is an important
clinical problem. Study of the salivary gland response to atrophy and
regeneration may provide a framework for designing strategies for the
radioprotection of salivary glands or methods by which to treat or reverse the
effects of gland atrophy.
PMID- 9638705
TI - Florid cemento-osseous dysplasia: Report of a case documented with computed
tomography and 3D imaging.
AB - Florid cemento-osseous dysplasia is an uncommon disease of the jaws. This article
reports the case of a 49-year-old black woman who was diagnosed with florid
cemento-osseous dysplasia on the basis of conventional radiographic findings.
Computed tomography and three-dimensional imaging of the mandible were performed,
and they enabled detailed localization of the bone defects. The role of computed
tomography in the evaluation of cemento-osseous lesions is discussed.
PMID- 9638706
TI - Pulp reaction to a tri-cure resin-modified glass ionomer.
AB - OBJECTIVE: This study evaluated the pulp response to a tri-cure resin-modified
glass ionomer cement and compared this response to those elicited by a zinc oxide
eugenol cement and a silicate cement. Materials were placed in nonexposed class V
cavity preparations on human teeth. STUDY DESIGN: Sixty premolars were selected
in orthodontic patients in a voluntary group of teenagers. All cavities were
prepared according to International Dental Federation specifications. Resin
modified glass ionomer and silicate applications were carried out according to
the manufacturers' instructions. RESULT: All teeth were asymptomatic. Pulp
responses to the resin-modified glass ionomer cement were slightly greater than
to the zinc-oxide-eugenol cement. Bacterial staining attempts were inconclusive
with regard to time intervals and pulp responses. No necrotic pulps were seen in
any teeth. CONCLUSION: The tri-cure resin-modified glass ionomer cement elicited
a slightly greater adverse pulp response than did the zinc-oxide-eugenol cement
with respect to the healing process of the pulp.
PMID- 9638707
TI - Development of periradicular lesions in immunosuppressed rats.
AB - PROBLEM: The role of bacteria has been well established in pulpal and periapical
diseases, but the contribution of the host defenses is less clear. OBJECTIVES:
The purpose of this study was to compare periradicular lesion development in
immunosuppressed rats with that in normal rats. STUDY DESIGN: Fifteen rats were
given weekly injections of Cytoxan (Bristol Laboratories) to suppress their
immune systems. The pulps of mandibular first molars of these animals and another
15 rats that had received no medications were exposed and left open to their oral
flora. The rats were killed at 2, 4, and 6 weeks. Radiographic analysis was
performed by means of a computer linked to a digitizing board and stylus. In
addition, specimens were decalcified, sectioned, stained, and examined under a
microscope with a grid to quantify relative percentages of surface areas of bone,
root, periodontal ligament, marrow spaces, soft tissue, and inflammatory
infiltrate. RESULTS: Statistical analysis showed a significantly greater
radiographic bone loss in the immunosuppressed group only at 4 weeks. No
significant histologic differences were found between the two groups. CONCLUSION:
Our results suggest that reduction of circulating leukocytes may not
significantly affect the development of periradicular pathosis in rats.
PMID- 9638708
TI - Labial and palatal "talon cusps" on the same tooth: A case report.
AB - Talon cusps are uncommon. Although they normally occur on the palatal surface of
maxillary incisors, the literature contains two case reports of labial talon
cusps. This is the first report describing a tooth with both a labial and a
palatal talon cusp and its successful management.
PMID- 9638709
TI - A diagnostic comparison of panoramic and intraoral radiographs.
AB - OBJECTIVE: This study compared panoramic and intraoral radiographic surveys in
the evaluation of specific dental pathoses in Air Force personnel. STUDY DESIGN:
The radiographs of 30 subjects were read singly and in various combinations:
panoramic survey only; periapicals plus bitewings; panoramic survey plus
bitewings; and panoramic survey plus periapicals plus bitewings. Three
independent, blinded examiners using standardized viewing conditions assessed the
radiographs in random order for the presence of caries, periapical pathoses, bone
loss, furcation involvement, impacted/unerupted teeth, internal/external root
resorption, and retained roots. The consensus radiographic standard of true
pathosis was the simultaneous interpretation by the three examiners of all
radiographs for each subject. RESULTS AND CONCLUSIONS: The panoramic survey by
itself was shown to have the lowest correlation with the consensus radiographic
standard when basic military trainees with generalized dental pathoses were
evaluated. The combination of panoramic survey plus bitewing radiographs
exhibited a diagnostic yield for specific pathoses that was comparable to that of
panoramic survey plus bitewings plus periapicals.
PMID- 9638710
TI - Distribution of scattered radiation during intraoral radiography with the patient
in supine position.
AB - OBJECTIVE: The purpose of this study was to investigate the spatial distribution
of scattered radiation during intraoral radiography with the patient in a supine
position to determine the exposure to an operator without a suitable barrier.
STUDY DESIGN: A phantom was placed in the supine position on a dental chair with
the occlusal plane perpendicular to the floor, and four intraoral periapical
radiographic examinations in the anterior and posterior regions of the maxilla
and mandible were performed. The scattered radiation was measured with an
ionization chamber at distances ranging from 25 to 200 cm at 25 cm increments and
at intervals of 45 degrees. Measurements were made at two different heights:
level with the occlusal plane and 30 cm below it. The exposure was converted to
an air-kerma/absorbed dose in air. RESULTS: The distribution of scattered
radiation was symmetric during examinations of the anterior region. Circular iso
exposure curves of up to 0.5 microGy were observed at the level of the occlusal
plane, and curves of up to 0.1 microGy were observed 30 cm below the plane. The
lowest exposures were measured 30 cm below the occlusal plane and behind the
chair. The distribution of scattered radiation was not symmetric during
examinations of the posterior region. Iso-exposure curves of up to 0.25 microGy
were observed at the level of the occlusal plane during exposure of the maxilla,
and curves of up to 0.5 microGy were observed during exposure of the mandible.
Circular iso-exposure curves of up to 0.1 microGy were observed 30 cm below the
occlusal plane. Lower values for scattered radiation were observed 30 cm below
the occlusal plane between 135 and 180 degrees behind the phantom. CONCLUSION:
The spatial distribution of scattered radiation with the patient in a supine
position was not the same in eight directions around the chair. Although the
preferred position for the operator is behind a suitable barrier, the preferred
position in the absence of a barrier is 200 cm behind the patient.
PMID- 9638711
TI - The lesions of the pterygopalatine and infratemporal spaces: Computed tomography
evaluation.
AB - OBJECTIVE: The purpose of this study was to categorize the computed tomography
features of lesions affecting the pterygopalatine fossa and infratemporal fossa
and thus aid in the diagnosis of these lesions. DESIGN: Eighty-six patients with
lesions of the pterygopalatine fossa and infratemporal fossa were examined with
computed tomography; the lesions were confirmed by both surgery and biopsy. The
patients were divided into three groups: group I consisted of patients in whom
the lesions had originated in one or both fossae; group II, of patients in whom
the lesions originated in other oral and maxillofacial regions but showed
extension into the pterygopalatine and infratemporal fossae; and group III, of
patients in whom the lesions had multicentric origins. RESULTS: Of the 11 cases
in group I, demarcation was confined to both fossae in 4 patients, and
involvement of the adjacent structures was shown on computed tomography images in
7 patients. Involved structures included the maxillary sinus (4 sides), nasal
cavity (3 sides), mandibular ramus (6 sides), buccal space (2 sides), base of the
skull (5 sides), palate (3 sides), and parapharyngeal space (5 sides). In the 70
cases in group II, computed tomography images showed that lesions had invaded
both fossae via following routes: (1) 40 lesions in the maxillary sinus had
infiltrated posterolaterally into 26 pterygopalatine and 39 infratemporal fossae;
(2) two nasal cavity and three nasopharynx tumors had infiltrated laterally or
lateroanteriorly into five pterygopalatine and one infratemporal fossae; (3)
lesions originating in mandibular rami (9 lesions), buccal regions (4 lesions),
parapharyngeal spaces (1 lesion) and parotid glands (1 lesion) had intruded
medially into 15 infratemporal fossae; (4) two temporal bone tumors had
encroached inferiorly on two infratemporal fossae; (5) four palate tumors had led
to involvement of three pterygopalatine and four infratemporal fossae; and (6)
four inflammatory diseases of the facial spaces involved two pterygopalatine and
four infratemporal fossae. Group III lesions (5 cases) affecting one
pterygopalatine and five infratemporal fossae were hemangiomas; one was a
malignant lymphoma. CONCLUSION: Group I lesions may involve the adjacent anatomic
structures of both pterygopalatine and infratemporal fossae in every direction.
Group II lesions that correspond to the various origins of the maxillofacial
region have different pathways of infiltration into the pterygopalatine or
infratemporal fossae. Computed tomography examination is very important in the
evaluation of lesions involving the pterygopalatine and infratemporal fossae.
PMID- 9638712
TI - Can an oxygenator design potentially contribute to air embolism in
cardiopulmonary bypass? A novel method for the determination of the air removal
capabilities of neonatal membrane oxygenators.
AB - At present, air handling of a membrane oxygenator is generally studied by using
an ultrasonic sound bubble counter. However, this is not a quantitative method
and it does not give any information on where air was entrapped in the oxygenator
and if it eventually was removed through the membrane for gas exchange. The study
presented here gives a novel technique for the determination of the air-handling
characteristics of a membrane oxygenator. The study aimed at defining not only
the amount of air released by the oxygenator, but also the amount of air trapped
within the oxygenator and/or removed through the gas exchange membrane. Two
neonatal membrane oxygenators without the use of an arterial filter were
investigated: the Polystan Microsafe and the Dideco Lilliput. Although the air
trap function of both oxygenators when challenged with a bolus of air was
similar, the Microsafe obtained this effect mainly by capturing the air in the
heat exchanger compartment while the Lilliput did remove a large amount of air
through the membrane. In conclusion, the difference in trap function was most
striking during continuous infusion of air. Immediate contact with a microporous
membrane, avoidance of high velocities within the oxygenator, pressure drop,
transit time and construction of the fibre mat all contribute to the air-handling
characteristics of a membrane oxygenator.
PMID- 9638714
TI - The effects of haemofiltration on cefazolin levels during cardiopulmonary bypass.
AB - Ultrafiltration has been shown to affect cardiac drug concentrations during
cardiopulmonary bypass (CPB), based on their respective pharmacological
properties. In an attempt to understand the aetiology of sternal wound
infections, a study was performed to eliminate the use of ultrafiltration as a
possible cause. We compared cefazolin levels at three time intervals during the
course of routine CPB with ultrafiltration to those levels in a control group in
which ultrafiltration was not used. Our results indicate that there is little
difference in the rate of decay of antibiotic levels with or without the use of a
haemoconcentrator. This implies that ultrafiltration procedures do not put the
patient at any increased risk for infection and that additional measures beyond
that which we would normally use at our institution need not be taken.
PMID- 9638713
TI - Clinical evaluation of a new generation membrane oxygenator: a prospective
randomized study.
AB - A new generation hollow-fibre membrane oxygenator (Spiral Gold) has been
introduced by Baxter Healthcare (Irvine, CA, USA). The purpose of this study was
to evaluate the operational performance of this device under clinical conditions
and to compare it to the Univox Gold membrane oxygenator. Following institutional
review board approval, and the obtainment of informed consent, 26 patients
undergoing coronary artery bypass grafting were randomly assigned to either a
Spiral Gold (Spiral) (n = 13) or Univox Gold (Univox) (n = 13) group. Study
parameters were grouped into the following categories: haematological,
haemodynamic, oxygenator performance and perioperative outcomes. All patients
received identical surgical, anaesthesia and postoperative care. There were no
statistically significant differences in either preoperative or operative
parameters between groups. During cardiopulmonary bypass, the Spiral group had a
significantly lower pressure drop (26.9 +/- 8.2 vs 46.7 +/- 16.2 mmHg, p <
0.001). The Spiral group had significantly lower plasma free haemoglobin levels
during all time periods of CPB compared to the Univox group. Heat exchange
coefficients were higher during the rewarming period in the Spiral patients (0.59
+/- 0.28) compared to the Univox group (0.36 +/- 0.19), p = 0.06. There were no
differences in oxygen transfer between groups, but ventilation gas sweep rates
and FiO2 levels were statistically lower in the Spiral group at two of the three
sampling time periods. The ratio of ventilating gas sweep rate to blood flow rate
was lower in the Spiral group (0.56 +/- 0.12) compared to the Univox group (0.74
+/- 0.23), p < 0.03. The Spiral Gold oxygenator had superior oxygen transfer
efficiency and lower haemolysis rates than the Univox Gold oxygenator.
PMID- 9638715
TI - The influence of mannitol on renal function during and after open-heart surgery.
AB - Mannitol is often included in the priming solution of the heart-lung machine used
during cardiopulmonary bypass (CPB). This study was set up to evaluate the effect
of different doses of mannitol on human patients. Patients receiving 10 g of
mannitol (n = 18) had an increased diuresis only during the bypass period (mean
time = 87 min) when compared with a control group (n = 19) who did not receive
mannitol. Patients receiving 20 g of mannitol (n = 19) had a significantly
greater diuresis than both the control group and the 10 g group and the diuresis
continued on throughout the immediate postbypass period (total mean time
approximately 3 h). Patients receiving 30 g of mannitol (n = 20) also had a
significantly greater diuresis that continued on during the first hour in the
intensive care unit (ICU) (total mean time approximately 4 h). After 6 h in the
ICU, all three groups of mannitol-treated patients equally demonstrated a trend
towards an increased diuresis over the control group, which became a significant
increase by 12 h in the ICU (p = 0.001) despite indications that the mannitol had
been cleared from the body. These results suggest that there is an improvement of
renal function post-CPB if mannitol is included in the CPB prime which may be due
to an amelioration of the ischaemic effects of bypass on the kidneys.
PMID- 9638716
TI - The effect of albumin priming solution on platelet activation during experimental
long-term perfusion.
AB - The objective of this study was to evaluate the effect of albumin priming on
platelet consumption and activation during long-term perfusion. Two identical in
vitro extracorporeal membrane oxygenation circuits were used; one was primed with
Ringer's solution containing human serum albumin, the other with Ringer's
solution only. Fresh heparinized human blood was pooled, divided between the two
systems and circulated for 24 h at 37 degrees C. Platelet count, plasma
concentration of betathromboglobulin (BTG), platelet membrane density of
glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5,
1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We
found that during the first hour of perfusion, slightly higher platelet counts (p
= 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed
with albumin, compared to the control circuits. No statistically significant
differences were observed for the platelet membrane expression of GPIb and
GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent
platelet consumption and activation during long-term perfusion.
PMID- 9638717
TI - Heparin-bonded circuits: clinical outcomes and costs.
AB - The aim of this study was to use meta-analysis to combine the results of numerous
studies and examine the impact of heparin-bonded circuits on clinical outcomes
and the resulting costs. Heparin-bonded circuits, both ionically and covalently
bonded, are examined separately. The results of the study provide evidence that
heparin-bonded circuits result in improved clinical outcomes when compared to the
identical nonheparin-bonded circuits. These improved clinical outcomes result in
subsequent lower costs per patient with their use. However, differences are
apparent in the significance and magnitude of these outcomes between ionically
and covalently bonded circuits. Covalently bonded circuits provide a greater
magnitude and significance of improvement in clinical outcomes than ionically
bonded circuits. Total cost savings can be expected to be three times greater
with covalently bonded circuits ($3231 versus $1068). It was concluded that the
choice regarding the use of a heparin-bonded circuits and the type of heparin
bonded circuit used has the potential to alter clinical outcomes and subsequent
costs. Cost consideration cannot be ignored, but clinical benefits should be the
main rationale for the choice of cardiopulmonary bypass circuit. This analysis
provides evidence that clinical benefits and cost savings can both be derived
from use of the same technology-covalently bonded circuits.
PMID- 9638718
TI - Clinical evaluation of a leucocyte-depleting blood cardioplegia filter (BC1B) for
elective open-heart surgery.
AB - Activation of leucocytes during extracorporeal circulation has attracted
attention in recent years as a cause of reperfusion injury in open-heart surgery
patients. In the present study, 40 adult patients undergoing elective open-heart
surgery were randomized into two groups: 20 using the Pall BC1B leucocyte
depleting filter for blood cardioplegia (group 1) and the other 20 without the
filter (group 2). In order to determine if the filter was effective in protecting
the myocardium, CPK-MB and troponin-T (TnT) were measured. In addition, efforts
were also made to determine appropriate sites at which the BC1B blood
cardioplegia filter should be positioned. There were no significant differences
between the two groups in terms of conditions of perfusion. No adverse effects
were seen in either group. The total leucocyte reduction rate through the filter
was 98.1% with the passage of 2 liters of blood through the filter. A pressure
drop of 4.4 +/- 3.2 mmHg was observed through the filter during use.
Statistically significant differences were noted between the two groups in CPK-MB
(p = 0.031) and TnT (p = 0.004). Findings obtained in previous studies
demonstrate that the various advantages of leucocyte reduction, shown in
experimental studies, can be translated into clinical advantages. In conclusion,
based on the results in this clinical study showing significant difference in CPK
MB and TnT which are known effective indicators for myocardial injury, between
leucoreduced and non-leucoreduced group, the Pall BC1B leucocyte-depleting filter
for blood cardioplegia has been shown to be effective in alleviating reperfusion
injury in open-heart surgery patients.
PMID- 9638719
TI - Extracorporeal membrane oxygenation in emergency resuscitation from deep
hypothermia.
PMID- 9638721
TI - Management of the erythropoietic porphyrias.
PMID- 9638720
TI - Stockert roller pump generated pulsatile flow: cerebral metabolic changes in
adult cardiopulmonary bypass.
PMID- 9638722
TI - The porphyrias: an introduction.
PMID- 9638723
TI - Management of the acute porphyrias.
AB - Three hepatic porphyrias--acute intermittent porphyria, hereditary coproporphyria
and variegate porphyria--are characterized by episodic acute attacks that consist
of various neuro-psychiatric symptoms and signs, such as abdominal pain,
vomiting, constipation, hypertension and tachycardia associated with increased
excretion of porphyrins and porphyrin precursors. Peripheral neuropathy is
manifested as pain in the extremities, and it may progress to a severe motor
neuropathy. Measurement of porphobilinogen in the urine gives a prompt diagnosis
during acute attacks. Attacks are often induced by precipitating factors such as
drugs, alcohol, infection, fasting or changes in sex-hormone balance, and they
should be eliminated when a patient is treated during an attack. Heme, the end
biosynthetic product, is the most effective therapy for restoration of porphyrin
biosynthesis to normal, and it is usually infused at 3 mg/kg daily for 4 days.
Adequate calories are necessary and parenteral nutrition with carbohydrates may
be necessary. Attacks may also require therapy for hypertension, pain and
epileptic seizures. Strict avoidance of all precipitating factors may not be
necessary in the asymptomatic phase.
PMID- 9638724
TI - Hepatic complications of erythropoietic protoporphyria.
AB - A quarter of patients with erythropoietic protoporphyria develop mild to severe
cholestatic liver disease. The determination of early indicators of hepatobiliary
involvement are of pivotal importance to select patients for choleretic therapy.
Porphyrin parameters were studied during ursodeoxycholic acid treatment in eight
patients with protoporphyrin-associated liver disease and eight patients with
liver failure before and after liver transplantation. The patients with
intrahepatic cholestasis exhibited excessive protoporphyrinemia (27 mumol/l)
compared with controls (normal < 0.64 mumol/l). Fecal protoporphyrin excretion
decreased in patients with deterioration of liver function, whereas urinary
coproporphyrin increased up to 2290 nmol/24 h (normal < 119 nmol/24 h).
Coproporphyrin isomer I proportion increased to 71 +/- 10% (mean +/- SD, n = 8)
in patients with terminal liver failure (normal < 31%). During therapy with
ursodeoxycholic acid biochemical improvement occurred but without clinical
remission in most cases. Eight patients underwent liver transplantation between
1987 and 1997. One patient died of liver failure. Two transplant recipients are
in a good condition since 8 and 9 years, respectively. All explanted livers
revealed micronodular cirrhosis and high protoporphyrin levels of about 25,000
fold (mean, n = 3). Immediately after liver transplantation protoporphyrin in
erythrocytes decreased to 46-96% of pre-operative values. Coproporphyrin remained
moderately elevated due to post-operative cholestasis. A post-operative rise in
fecal protoporphyrin elimination reflected sufficient biliary clearence of
protoporphyrin by the transplant. In conclusion, moderate coproporphyrinuria with
isomer I is the earliest sign of liver complications in erythropoietic
protoporphyria. Progression of protoporphyrin induced toxic liver injury is
indicated by excessive protoporphyrinemia and coproporphyrinuria with an isomer I
proportion > 71 +/- 10%, and reduction of fecal protoporphyrin excretion. Results
suggest that therapy of intrahepatic cholestasis with ursodeoxycholic acid is
only effective in the initial stages of liver disease in erythropoietic
protoporphyria. In patients with severe cholestatic hepatic failure, liver
transplantation is the treatment of choice.
PMID- 9638725
TI - Evaluation of porphyria.
PMID- 9638726
TI - Management of patients with porphyria cutanea tarda.
PMID- 9638727
TI - Update on enzyme and molecular defects in porphyria.
AB - Each porphyria results from decreased activity of one of the enzymes of haem
biosynthesis. The molecular basis of enzyme deficiencies in acute intermittent
porphyria (AIP), variegate porphyria (VP) and congenital erythropoietic porphyria
(CEP) is outlined. All three conditions show extensive allelic heterogeneity. In
the autosomal dominant disorders, AIP and VP, no genotype/phenotype correlations
have been demonstrated, and the explanation for their low clinical penetrance
remains uncertain. In AIP and VP, mutational analysis is superior to biochemical
methods for screening families for latent porphyria. In the autosomal recessive
condition, CEP, there is some genotype/phenotype correlation--one common mutation
(C73R) being associated with severe disease in homozygotes. Porphyria cutanea
tarda (PCT) is not a simple monogenic disorder. Patients appear to have an
inherited susceptibility to inactivation of hepatic uroporphyrinogen
decarboxylase (UROD) as part of a response to hepatocyte injury by alcohol, HCV
and other agents. Inherited factors that, in combination, may predispose to PCT
include mutations in the UROD gene, present in about 20% of patients, and the
C282Y mutation in the haemochromatosis (HFE) gene.
PMID- 9638728
TI - Molecular genetics of erythropoietic protoporphyria.
AB - Erythropoietic protoporphyria (EPP) is caused by decreased activity of the enzyme
ferrochelatase and is characterized by burning photosensitivity commencing in
childhood. From 1-10% of patients develop potentially fatal protoporphyric
hepatic failure. The gene for ferrochelatase has been cloned, sequenced and
mapped to the long arm of chromosome 18. EPP is genetically very heterogeneous
and 24 different mutations in 27 unrelated patients have been published. In the
majority of families co-inheritance of a mutant ferrochelatase allele from one
parent and a low-output "normal" ferrochelatase allele from the other parent is
required for disease expression. The molecular basis, if any, of protoporphyric
hepatic failure has not yet been resolved. Gene therapy experiments have been
completed in vitro and are in progress in an animal model of EPP. In conclusion,
molecular genetic investigation of EPP has increased our understanding of its
pathogenesis and inheritance. Why some EPP patients develop hepatic failure is
still unanswered. Gene therapy of EPP patients may become possible in the future.
PMID- 9638729
TI - Skin pigmentation in Caucasian babies is high and evenly distributed throughout
the body.
AB - To investigate if Caucasian babies have particular sun sensitive skin and if skin
pigmentation before any sun exposure is uniform throughout the body, we measured
skin pigmentation objectively by skin reflectance spectroscopy in 10 anatomical
sites in 20 healthy Caucasian babies (mean age 5 months, range 1 to 10 months)
that had not been sun exposed previously. We found that skin pigmentation at all
the measured sites was significantly higher than the constitutive pigmentation in
Caucasian adults (P < 0.01). Furthermore, the level of skin pigmentation in all
the 10 measured sites in the babies was statistically not different (P < 0.31)
and there was no gender differences in pigmentation for any site.
PMID- 9638730
TI - Two patients with isoniazid-induced photosensitive lichenoid eruptions confirmed
by photopatch test.
AB - Causative agents of drug eruptions are frequently unknown, and skin tests with
candidate drugs would be useful before systemic challenge. It remains to be
clarified how phostosentive lichenoid drug eruptions are induced, but allergy,
including delayed type allergy, has been suggested. Two patients who had taken
anti-tuberculous drugs developed a lichenoid drug eruption, primarily on sun
exposed skin. Patch and photopatch tests were performed with each of the ingested
drugs (10% in petrolatum). Photopatch tests to isoniazid (INH) were positive.
These were confirmed by oral challenge followed by irradiation with UVA. In
conclusion, photopatch tests facilitated identification of the causative drug in
two patients with photosensitive lichenoid eruptions to INH.
PMID- 9638731
TI - A hazard assessment of artificial tanning units.
AB - As a result of increasing concern over the use of artificial tanning units, many
local government recreation departments are phasing out the use of sunbeds on
their premises, resulting in some clients switching to high street parlours about
which little is known. An Environmental Health survey was conducted in all 32
tanning premises within a local government area (Perth & Kinross, Scotland). A
number of significant problems emerged in the private sector. In this group,
there was no form of cumulative UV exposure control in 89% of premises and 81%
failed to give adequate advice and information to customers. We conducted UV
spectral irradiation measurements in 38 tanning units using a double grating
spectroradiometer. When a carcinogenic weighting factor was applied to these
measurements, it was found that a 10 min exposure in a high intensity stand-up
cabinet carried the same carcinogenic risk as approximately 30 min of local (56
degrees North) mid-day summer sunlight or 10 min of Mediterranean sunlight at mid
day. A questionnaire completed by 57 customers revealed a wide pattern of usage;
6 (10%) had more than 20 h exposure in the previous 12 months and 3 (5%) had made
regular use of sunbeds for the previous 16 to 20 years. These results indicate
that there is a need for continuing public education and surveillance of
commercial artificial tanning units.
PMID- 9638732
TI - Withdrawal of presession saccharin suppresses food-maintained responding in rats.
AB - Decreased motivation following drug withdrawal is often characterized as
indicative of addiction. Similar behavioral disruptions are seen in negative
contrast paradigms. In the current study, 7 rats with a history of access to a
palatable 0.15% saccharine solution before operant sessions were conditioned.
Rats responded for food under a multiple FR 5 FR 40 reinforcement schedule. When
presession saccharin was removed and replaced with water, responding maintained
by food was significantly decreased, with greater effects observed under the FR
40 schedule. These results support the assertion that behavioral disruptions
accompanying withdrawal syndromes include a negative contrast component.
PMID- 9638733
TI - Reliability estimates of the Purpose in Life and Seeking Noetic Goals tests with
rural and metropolitan-area adolescents.
AB - The Purpose in Life and Seeking Noetic Goals tests were administered to 198 rural
Missouri and 659 metropolitan-area Washington high school students and
readministered after an 8-week interval. The obtained test-retest and Cronbach
alpha coefficients were largely consistent with earlier research using adult
clinical samples.
PMID- 9638734
TI - Performance on two attention tasks as a function of sex and competition.
AB - Effects of sex and competition on receptive attention and Stroop task performance
of 59 college students were investigated, 33 participants in a competitive
condition were informed that performance would be ranked by sex; 36 in a
noncompetitive condition were given no information regarding competition.
Consistent with previous research, no significant main effects or interactions
were found for scores on the receptive attention task. Contrary to previous
findings, though, the Stroop task also yielded no significant main effects;
however, a significant interaction was found. Men experienced more interference
in the competitive condition, whereas women showed no significant effects of
competition. Women did experience more interference than men in the
Noncompetitive condition. Conclusions suggest that men may be more sensitive to
sex-based performance comparisons.
PMID- 9638736
TI - Semantic activation by Japanese kanji: evidence from event-related potentials.
AB - In a character-judgment paradigm, the subject quickly pressed a key when a
hiragana (Japanese syllabary) appeared on a display and did nothing when a kanji
(Japanese logograph) appeared. The amplitude of the N400 component was compared
when four types of visual stimuli were used: (Type 1) single kanji--Grade 1- to 3
level words, (Type 2) single kanji--Grade 1- to 3-level bound morphemes, (Type 3)
single kanji--high school- and college-level bound morphemes, and (Type 4)
obsolete kanji. Analysis showed that N400 was largest in the temporal-occipital
areas for the Type 1 stimuli and larger in the right parietal area for Type 2
than Type 3 stimuli. The analyses of N400 to semantic stimulations have been
conducted and discussed in terms of their meaningfulness, age when writing of
these kanji was mastered, and linguistic status (kanji versus nonkanji). Most
interestingly, the Types 3 and 4 kanji did not activate semantic responses,
showing that they did not function as linguistic units, i.e., kanji, in the
mental lexicon.
PMID- 9638737
TI - Indirect tactual discrimination of heights by blind and blindfolded sighted
subjects.
AB - The ability of blind and blindfolded sighted subjects to discriminate cubes of
different heights was measured using the method of constant stimuli. Five male
blind and 5 male blindfolded sighted students, ages 22 to 28 years, were
subjects. All blind subjects had undergone orientation and mobility training at a
school for the blind. The cubes, made of wood, were explored using a long cane.
Subjects were presented the standard cube and a comparison cube and required to
judge whether the comparison cube height was taller, the same, or shorter than
the standard. Analysis showed that the difference thresholds of blind and
blindfolded sighted subjects were 1.93 and 2.14 cm, respectively. No significant
difference in accuracy of discrimination was found between the two groups. The
blind subjects showed significantly better performance than the blindfolded
sighted subjects on the discrimination task. The blind subjects performed the
task significantly faster than the blindfolded sighted subjects. The results
suggest that braille reading, use of a long cane, and daily physical activities
which required prolonged haptic or proprioceptive learning, may enhance nonvisual
motor skills.
PMID- 9638738
TI - Methodological concerns when using silhouettes to measure body image.
AB - This paper discusses methodological concerns of using silhouette figures to
measure body images. These include concerns related to scale coarseness (limiting
response options to one of a finite number of drawings), restriction of range,
method of presentation, and scale of measurement. Recommendations are made to
address these limitations, and an alternative silhouette scale using continuous
scale measurements is proposed.
PMID- 9638739
TI - Spacing effects on implicit picture memory.
AB - 25 undergraduates studied the stimulus pictures of common objects successively
presented as spaced or massed repetitions, or one at a time. Immediately after a
study period, they were given a free-recall test followed by a perceptual
identification test. Analysis indicated that spacing effects were observed on the
free-recall test but not in perceptual identification. On the later test, each
stimulus picture was exposed for a short period and subjects were more likely to
use perceptual cues than on first the test. Thus, the spacing effects on memory
may be eliminated at test as there is no benefit of conceptual cues.
PMID- 9638740
TI - Ear preference: association with other functional asymmetries of the ears.
AB - The bases for the preferential use of one ear are not clear. We investigated ear
preference, asymmetry on a dichotic listening test and acuity dominance
(laterality of hearing loss) in a sample of 51 patients with mild high frequency
hardness of hearing. There was a higher correlation between measured ear
preference and the measured acuity dominance than between ear preference and
dichotic listening, suggesting a certain peripheral (cochlear) base for the ear
preference.
PMID- 9638741
TI - Practice and serial reaction time of adolescents with autism.
AB - This study examined effects of practice on timing of serial reactions by 7
adolescents diagnosed with autism by using a task requiring they track a series
of timed lights. The adolescents showed significantly slower and more variable
mean simple reaction time than 10 normal control subjects of the same age. On a
task of tracking a serial light stimulation for 4 days, on the other hand,
significant effects of practice on timing of serial reactions were observed for
mean serial reaction times of them. In addition, from individual variations in
reaction times and anticipatory reaction times, four of seven subjects with
autism showed significant effects of practice. Analysis suggested that these
autistic adolescents may be chunking together the whole series of responses and
are unable to coordinate the timing of individual responses with individual
stimuli. Our data indicate that at least some adolescents with autism are able to
form and utilise a motor program with practice.
PMID- 9638742
TI - Body consciousness in Dohsa-hou, a Japanese psychorehabilitative program.
AB - To seven cerebral palsied children in a special elementary school, Dohsa-hou, a
Japanese psychorehabilitative program, was introduced in a pre-post design. With
the help of their mothers in writing they rated on a 5-point scale changes in
their body consciousness by applying 8 1-hr. sessions of Dohsa-hou training to
each child. Analysis suggests a significant positive change after training in
body consciousness of these children especially for private as compared to public
body consciousness.
PMID- 9638743
TI - Comparison of demands of sustained attentional events between public and private
children's television programs.
AB - The durations and variability of changing events were analyzed for 20 min. each
of 13 children's television programs. These programs included selections from
both publically and privately produced shows. Significantly different patterns of
attentional demands were found between the programs. Public television
programming is characterized by longer and more variable durations of sustained
attentional events, while private television programming is best described as
having fast-paced shorter events. The implications of this finding for
difficulties in learning by school-age children to attend for longer periods are
discussed.
PMID- 9638744
TI - An examination of the reliability and validity of scores on the Italian version
of the Dieter's Inventory of Eating Temptations.
AB - The aim of this paper was to highlight some psychometric characteristics of
scores on the Italian version of the Dieter's Inventory of Eating Temptations.
The analysis included assessment of the internal consistency of the individual
scales, test-retest reliability, and estimates of both convergent and
discriminant validity. Analyses showed that the Italian version of the inventory
can be considered reliable and valid, which suggested its use as screening test
for the identification of subjects who may be at risk for over-eating.
PMID- 9638745
TI - Differences in auditory scalp potentials evoked by meaningful words and
nonlinguistic stimuli.
AB - Differences in auditory evoked potentials with meaningful words and their reverse
playback may reflect different neural processes in recognizing auditory stimuli.
Auditory evoked potentials with the words and their reverse playback were
analyzed for eight volunteers, and a maximal difference was observed at a latency
around 400 msec. over the left middle temporal central area.
PMID- 9638746
TI - Two measures of laterality in handedness: the Edinburgh Handedness Inventory and
the Purdue Pegboard test of manual dexterity.
AB - This study investigated the relationship between a paper-and-pencil measure of
laterality in handedness, the Edinburgh Handedness Inventory, and a test of
manual dexterity, the Purdue Pegboard test. Individuals of extreme handedness
based on the Edinburgh Handedness Inventory (laterality Quotients of +90 to +100
and -100 and +54; 50 each) were recruited to complete the Purdue Pegboard test of
manual dexterity. Subjects in the sinistral group had significantly smaller mean
discrepancy scores in performance between their hands [t80 = 5.12, p = .0001] and
much greater variance in performance than dextral subjects (F1,98 = 2.85, p =
.0001). These findings suggest that paper-and-pencil measures of lateral
preference for handedness may not identify proficiency of subgroups within a
sinistral group.
PMID- 9638747
TI - Figure-ground perceptual organization and learning by three-year-old children.
AB - We have elaborated a program for the instruction of 54 3-yr.-olds using visual
aids (cards showing the graphic representation of a number printed on three
different types of backgrounds). Analysis showed differences in the increase in
scores obtained by the children before and after the application of the program
depending on the type of background.
PMID- 9638748
TI - Similar Muller-Lyer effects from operant and comparison response modes.
AB - A one-sided (monopole) version of the Muller-Lyer was used to assess the effect
of response mode on the metric distortion associated with the illusion. Two
different response modes were tested for comparability. The Operant Mode required
the judgment of stimulus span to be indicated by marking a dot on the test page.
The Comparison Mode required judgment of equality of two adjoining prepositioned
spans. The perceptual effects with the comparison procedure are known to consist
of underestimation of spans which are bounded by concave fin-sets and over
estimation of spans which are bounded by convex fin-sets. The question is whether
the motor demands of the operant task produce an additional source of metric
bias. Analysis indicate a very high correlation of judgments for the two modes of
testing. Also, data with either mode of responding closely fit a linear model of
the effect, and the model provides comparable index values for the concave and
convex versions. These results should mitigate concern about potential motor bias
from the operant method and encourage its use as a more efficient procedure for
assessing metric distortion.
PMID- 9638749
TI - Effect of music on spatial performance: a test of generality.
AB - Previous attempts by various researchers to replicate the enhancement of spatial
performance following 10 min. exposure to music have been inconsistent in their
findings. In the present study 16 subjects showed reliable improvement on a paper
folding-and-cutting task after listening to Mozart's Sonata for Two Pianos in D
major, as employed by others. The enhanced performance was also noted for 16
other subjects after listening to a contemporary selection having similar musical
characteristics. In both cases the control procedure included 10 min. of
listening to a progressive relaxation tape.
PMID- 9638750
TI - Information-processing characteristics of explicit time estimation by patients
with schizophrenia and normal controls.
AB - The information-processing characteristics of time estimation have not been well
documented. This research investigated explicit time estimation to test whether
(1) it can occur "automatically" and (2) the cognitive function generally known
as "working memory" predicts accuracy of time estimation. Data on two tasks
requiring explicit time judgement (time interval estimation and production) are
reported for a sample of 43 normal, healthy controls and 19 inpatients with
chronic schizophrenia. Each task was given in a standard (passing time interval
is unfilled) and dual-task format (interval is filled by oral reading).
Multivariate analysis of variance suggested that for both patients' and the
normal controls' time estimation accuracy was (1) highly sensitive to whether a
passing interval was filled with a concurrent activity such as reading and (2)
predictable on the basis of age, education, and working memory skills. Also, the
effect of the dual-task manipulation did vary as a function of psychosis for the
Time Interval Production task. The data suggest that procedures for explicit time
judgements do not occur automatically and utilize controlled processes such as
working memory.
PMID- 9638751
TI - Mental rotation: a task for the assessment of visuospatial skills of children.
AB - 7 girls and 5 boys, ranging in age from 7 to 12 years, participated in the pilot
testing of a mental rotation task developed for use in a comprehensive test
battery of visuoperceptual abilities. Two asymmetric, three-dimensional objects
were constructed from wood strips such that one object was the mirror-image of
the other. Black and white photographs were taken of these objects in various
spatial orientations along a horizontal plane. 16 photographs depicted the object
right-side-up and in 16 the object was upside-down (rotated 180 degrees in the
vertical plane). These photographs were presented to the children who were asked
to match each with the corresponding object. Analysis indicated correct
judgements of the right-side-up images occurred more frequently than the upside
down images (t11 = 4.73, p < .001). Using these data, adjustments were made to
the task instructions to provide greater clarity for the young participants.
PMID- 9638753
TI - Psychometric properties of the grade 4 reading level Multiple Affect Adjective
Check List-Revised with offenders.
AB - The reliability and validity of the Grade 4 reading level Multiple Affect
Adjective Check List was assessed with offenders in four settings within the
criminal justice system. With the exception of the Sensation Seeking Scale, the
MAACL-R4 scales showed good internal consistency and test-retest reliability and
adequate convergent and discriminant validity, but not for the Depression scale
for 53 female arrestees and the Hostility scale with 51 male arrestees.
Correlations with self-ratings of health and stress and with the Family
Environment scales were in expected directions. It is concluded that the MAACL-R4
has the basic qualities necessary for use in research with offenders.
PMID- 9638752
TI - Unilateral neglect in children with hemiplegic cerebral palsy.
AB - The purpose of this study was to examine the pattern of attentional deficits in
children with right and left hemiplegic cerebral palsy. Unilateral neglect and
visuospatial deficits are common findings following right brain injury in adults.
It has been suggested by some that children may show a similar pattern. Children
were tested on several paper-and-pencil measures of neglect. It was hypothesized
that (a) on the left side of the page, children with left hemiplegia (right
hemispheric damage) will score significantly lower than both the control group
and the right hemiplegia group and (b) on the right side of the page, there will
be no significant difference between the control group and the right and left
hemiplegic groups. Participants included 32 children with cerebral palsy, 15 with
left hemiplegia, 17 with right hemiplegia, and 32 matched controls. The ages
ranged from 5 years 10 months to 12 years 6 months; all had normal intelligence.
Inventories included 3 subtests of the Conventional part of the Behavioral
Inattention Test, the Mesulam Symbol Cancellations tests, and the Rey Osterrieth
Complex Figure, copy and recall. Analysis indicated that children with left
hemiplegia scored significantly more poorly than controls on seven of the eight
measures on the left side of the page, but they did not consistently score more
poorly than children with right hemiplegia. Moreover, the poorer performance of
the children with left hemiplegia was not specific only to the left side of the
page; they also scored significantly lower than the controls on five of the eight
measures on the right side. These findings suggest that children with left
hemiplegia may have relatively greater attentional and perceptual problems than
children with right hemiplegia, but they do not clearly indicate a left
unilateral neglect. Results also indicate that children with right hemiplegia
have attentional and perceptual problems relative to controls, particularly on
the more complex tasks of high demand.
PMID- 9638754
TI - Economic growth and suicide and homicide rates revisited.
PMID- 9638755
TI - Congenital dyschromatopsia and school achievement.
AB - In 1993-94, in Liguria (a northwestern Italian region) a study was carried out on
dyschromatopsia, a congenital sex-linked form of colour blindness. 3124 junior
high school boys aged 10-15 years were tested using Ishihara plates (1973
edition) and Farnsworth's D-15 test (1947 edition). 152 students were identified
as colour blind (4.87%), a value slightly below the Italian average of 5.3%. The
school achievement of these students was assessed by means of the school marks of
two randomised subsamples composed of 82 dyschromates and 82 orthochromates,
paired homogeneously by age and class. Statistical analysis indicated
significantly lower general school achievement for the 82 dyschromate subjects
(except for art). The learning difficulties of dyschromate persons for whom
colour is a basic didactic tool are discussed. Introduction of dyschromatopsia
tests at preschool would be desirable.
PMID- 9638756
TI - Physical exertion in simple reaction time and continuous attention of sport
participants.
AB - To investigate the effect of physical exertion on simple reaction time and
continuous attention of sport participants, an experiment was conducted with 46
male university students and 12 male cyclists. The subjects were assigned to
three experimental and two control groups. The subjects of the experimental
groups were asked to perform, following a 5-min, period of warming up, a high
intensity exercise protocol for 5 min., on a mechanically braked cycle ergometer
(Group A) or a moderate intensity exercise protocol for 30 min, on the same cycle
ergometer (Groups B and C). Shortly before and immediately after the physical
exercise subjects of all groups were asked to perform a test of simple reaction
time and continuous attention. The subjects of the control groups were asked to
perform at rest both tests of the simple reaction time and the continuous
attention twice, with a 10-min. and a 35-min. interval between the first and
second attempts, respectively. The results did not support the notion that
exercise of moderate or high intensity influences significantly the cognitive
performance of aerobically trained or untrained subjects. The results are
discussed in the light of the current research findings concerning exertion and
human psychomotor performance.
PMID- 9638757
TI - Handwriting in assessing treatment for substance abuse.
PMID- 9638758
TI - Identification of a speaker's sex: a study of vowels.
AB - An experiment was carried out to test whether three phonetically naive listeners
were able to identify a speaker's sex from brief natural vowel segments. All
speech segments presented to the listeners were extracted from sentences spoken
by members of a group of three women and three men with a British General
Northern accent. Analysis showed that listeners were able to identify the
speaker's sex from the vowel segments with high accuracy (a mean score of 98.9%,
p < .001). Acoustic analyses were subsequently carried out to quantify the
acoustic and phonetic differences related to the sex of the speakers. Fundamental
frequencies and format frequencies of the vowel stimuli were investigated. The
men generally had lower values of both than the women.
PMID- 9638759
TI - Identification of a speaker's sex: a fricative study.
AB - An experiment was carried out to test whether three phonetically naive listeners
were able to identify the speaker's sex from brief (30 msec. to 100 msec.)
voiceless fricative segments. All speech segments were extracted from sentences
spoken by members of a group of 3 women and 3 men with a British General Northern
accent. The consonant segments were significantly identified by the listeners
with an accuracy of 64.4%. A sample of the fricative segments was chosen to
investigate acoustic and phonetic differences related to a speaker's sex, using
spectrographic analysis. Analysis showed that on the average the frication of the
women's voiceless fricatives was significantly higher in frequency than that of
the men.
PMID- 9638760
TI - Influence of time of day on anaerobic capacity.
AB - 12 volunteers performed exhaustive exercise tests in the morning and afternoon.
Paired-means t tests indicated that anaerobic capacity, as reflected by maximal
accumulated oxygen deficit, was 26% higher (p < .01) in the afternoon than in the
morning. VO2max appeared higher and VO2 kinetics seemed faster in the afternoon,
but differences did not attain statistical significance. Thus, the time of day
affects anaerobic capacity and may influence other responses to exercise.
PMID- 9638761
TI - Effectiveness of redundant color coding in multidimensional identification.
AB - This study investigated the effectiveness of redundant color coding in
multidimensional identification. Statistical analysis showed that redundant color
in multidimensional identification did not necessarily improve performance and
response speed might even deteriorate if subjects were not informed of the use of
redundant color. Merely informing subjects of the use of redundant color might
not benefit identification speed either; subjects had to actually use color in
responding to facilitate response speed. Further, redundant color might be more
appropriate to associate with the less-salient or the less-familiar stimulus
attribute. Implications of the results for the design of multidimensional display
and for human information processing were discussed.
PMID- 9638762
TI - Adolescents' perceptions of psychosocial factors related to sickle cell disease.
AB - 12 adolescents with sickle cell disease rated psychosocial reactions to their
disease. They had positive social and family relationships but had concerns about
body development, self-confidence, being a burden on their families, and death.
PMID- 9638763
TI - Preliminary development of a scale to measure attitudes regarding the importance
of role modeling in physical activity and fitness behaviors among Health,
Physical Education, Recreation, and Dance professionals.
AB - This paper presents a new 16-item scale designed to measure attitudes regarding
the importance of role modeling in physical activity and fitness behaviors among
Health, Physical Education, Recreation, and Dance professionals. The measure was
reviewed for face validity by a panel of experts and preliminary analyses gave as
Cronbach alpha of .95 and split-half reliability of .97 for 22 graduate students.
PMID- 9638764
TI - Speakers' sex differences in voice onset time: a study of isolated word
production.
AB - This report presents a brief study into sex differences of speakers in the voice
onset time of English plosives that are stressed in both word-initial and
prevocalic positions. 36 isolated words were spoken by 5 men (age range 25 to 37
yr., M: 34.2 yr.) and 5 women speakers (age range 28 to 38 yr., M: 32.6 yr.) who
were subjects. Analysis showed that the women speakers had on the average
relative to the men, longer voice onset time values for voiceless plosives and
shorter voice onset time values for the voiced plosives.
PMID- 9638765
TI - Comparison of the vertec and Just Jump Systems for measuring height of vertical
jump by young children.
AB - To assess differences between the Vertec and the Just Jump Systems in measuring
height of vertical jump, 248 boys and 232 girls between 7 and 11 years were
required to perform four maximal countermovement vertical jumps. A maximum of the
four trials recorded was the dependent variable. Each vertical jump was
simultaneously evaluated by each measuring device and a paired t test indicated
the systems were significantly different; however, the experiment wise difference
of .93 in has no practical value. The Just Jump System seems a viable
alternative. Advantages and potential pitfalls regarding the use of each system
are discussed.
PMID- 9638766
TI - Correlations between hand preference and durations of hearing for right and left
ears in young healthy subjects.
AB - In this study, to test an inference from the 1991 Previc hypothesis that right
handers have a right-ear advantage, the durations of hearing for the right and
left ears were compared for 81 right- and 45 left-handed high school students. In
the present study, right-handedness was associated with a right-ear advantage and
left-handedness was associated with a left-ear advantage. In addition, there was
a significant positive correlation between the durations of hearing for the right
and left ears and the scores for right-handedness for right-handed subjects. The
durations of hearing for the right and left ears were negatively correlated with
the left-handedness for left-handed subjects. These results suggest hand
preference may be related to asymmetry of aural sensitivity.
PMID- 9638767
TI - Education students' description of learning 'disabilities'.
AB - 295 first- and fourth-year students in the College of Education at the University
of Saskatchewan, Canada were asked to describe learning disabilities. When the
descriptors they used were categorized, nonparticipation in the classroom formed
the largest single category.
PMID- 9638768
TI - Sports members' participation in assessment of incidence rate of injuries in five
sports from records of hospital-based clinical treatment.
AB - This study is about the incidence rate of sports injuries in five different types
of sports, gymnastics, soccer, volleyball, hockey, and basketball, for which
5,154 patients were admitted to the Emergency Unit of the Groningen University
Hospital during the period 1990 through 1994. Incidence rate had been computed by
membership participation. Basketball had the highest incidence rate (231 injured
persons per 10,000 participants), followed by hockey (158 injured persons per
10,000 participants). The highest mean Injury Severity Score, 2.39, was found for
gymnastics which had the lowest incidence rate (7 injured persons per 10,000
participants). Gymnastics had the highest percentage (12%) clinically treated
patients, whereas basketball had the smallest percentage (2%) of clinically
treated patients. The most frequent type of injury was distorsion, except for
hockey, in which contusion had the highest percentage of occurrence. For all five
types of sports, the majority (about 90%) of the injuries were observed at either
the lower or at the upper extremities.
PMID- 9638769
TI - Redundancy gain in discrimination of colored lights: effects of complexity and
eccentricity.
AB - The present study investigated the redundancy gain in discrimination of colored
lights. Subjects were requested to discriminate a target from 34 nontarget lights
differing from the target in luminance, hue, or both, and RTs were recorded.
Experimental variables were the complexity of stimulus pattern and the
eccentricity of the target in visual angle. The 35 lights were arranged regularly
on an imaginary grid in the low-complexity condition and were arranged randomly
in the high-complexity condition. The eccentricity of target was varied from 0
degree to 16 degrees. Only when the stimulus pattern was highly complex and
eccentricity was large, the combination of luminance and hue made the subject's
discrimination faster than when luminance or hue individually operated as a cue
for discrimination. That is, a redundant target effect was found only for a
highly complex stimulus pattern and in peripheral vision.
PMID- 9638770
TI - Novelty and complexity in human infants' exploratory behaviour.
AB - The effect of novel and complex stimulus cubes on the exploratory behaviour of
human infants was analysed in two studies (ns = 30 and 20). Infants showed
relatively greater preference for complex patterned cubes, and their exploratory
behaviour habituated over 5 days.
PMID- 9638771
TI - Attitudes of undergraduate physical education majors in Brazil toward teaching
students with disabilities.
AB - This study assessed the relationship of attitudes of physical education majors in
Brazil to specific disabling conditions, i.e., Emotional and Behavioral
Disorders, Specific Learning Disabilities, Moderate Mental Retardation, and
Orthopedic Impairment. This study also identified which selected teachers'
attributes, i.e., age, sex, years of teaching, course work in adapted physical
education, course work in special education, years teaching students with
disabilities, quality of teaching experience, and perceived competence were
related to favorable attitudes. Analysis showed no significant differences toward
teaching students with these disabilities. Simultaneous multiple regression
procedure also showed perceived competence was the only statistically significant
predictor of attitudes toward teaching such students.
PMID- 9638772
TI - A signal-detection theory based perspective on design of warning.
AB - The effects of warnings are analyzed using a distributed signal-detection theory
model. It is established that selectivity always increases effectiveness. The
implications to optimal warning design for intermittent versus continuous hazards
are discussed. The changes in the behavior of the 6 human subjects in response to
changes in the warning levels are consistent with the predictions of the model.
PMID- 9638773
TI - Sex differences in exercise motivation and body-image satisfaction among college
students.
AB - The current study was an expansion of one by Cash, Novy, and Grant in 1994, in
which responses of 101 female nursing students were examined for associations
between reasons for exercise, frequency of exercise, and body-image satisfaction.
In the current study, 78 male and 100 female undergraduates between the ages of
18 and 25 years (M = 21.2, SD = 1.9) from various majors completed a
demographics/frequency of exercise survey, two body-assessment inventories, and
the Reasons for Exercise Inventory of Silberstein, Striegel-Moore, Timko, and
Rodin. Contrary to Cash, et al.'s findings, only health and fitness reasons were
predictive of women's frequency of exercise, and women's dissatisfaction with
specific bodily attributes was not significantly related to any reasons for
exercising; however, like women in their sample, the current students who
experienced more situational body dissatisfaction exercised for appearance and
weight control. Sex comparisons indicated similar dissatisfaction with specific
bodily attributes among men and women, but values were not significantly
associated with any reasons for exercising. Women reported higher situational
body dissatisfaction and exercising for appearance-related reasons more than men.
Current participants may represent a more diverse group than previously tested,
and the inventory's factor structure may not be generalizable to men and women.
PMID- 9638774
TI - Stability and variability of dream content.
AB - The present study investigated the stability and variability, respectively, of
selected dream content measures derived from diary dreams. The within-subject
correlations were small when dream length was controlled. To obtain sufficient
reliability for all scales dream series of 20 dreams or more would be necessary.
PMID- 9638775
TI - Clinical, bacteriological and epidemiological aspects of clinical mastitis in
Israeli dairy herds.
AB - A 4-year retrospective study was performed to determine the clinical,
bacteriological and epidemiological aspects of acute clinical mastitis in seven
Israeli dairy herds. A total of 1124 clinical mastitis cases were detected by
abnormal changes in the milk and udder with concurrent decrease of at least 25%
in daily milk production. A total of 1190 quarters were affected with clinical
mastitis in 1089 cows. The rear quarters had a higher incidence risk (64.7% of
quarter cases) than the front quarters. The annual herd-year-incidence varied
from 4.2 to 126.8 cases/100 cows/year. The whole-lactation incidence risk (LIR)
was 20.8 per 100 lactations. LIR increased from the first to fifth lactation and
then decreased. Most clinical mastitis cases were associated with coliform
bacteria (60.2% of cases), environmental streptococci (18.6%), coagulase-negative
staphylococci (8.7%) and samples from which no bacterial growth was detected
(8.1%). Most cases of clinical mastitis occurred in the early stages of
lactation, with 51.4% of all cases, 52.3% of coliform cases and 54.6% of
environmental streptococci mastitis cases occurring during the first 4 months of
lactation. The median days in milk at diagnosis was 118 days. The incidence was
lower in the dry summer months. The ratio of peak to low incidence was 1.62 with
a calculated peak incidence in January.
PMID- 9638776
TI - Multiple sources of Escherichia coli O157 in feedlots and dairy farms in the
northwestern USA.
AB - Samples from cattle, other domestic and wild animals, flies, feeds, and water
troughs were collected from 12 cattle farms and tested for Escherichia coli O157.
E. coli O157 was isolated from bovine fecal samples on all 12 farms with a within
herd prevalence ranging from 1.1% to 6.1%. E. coli O157 was also found in 1 of 90
(1.1%) equine fecal samples, 2 of 65 (3.1%) canine fecal samples, 1 of 200 pooled
bird samples (0.5%), 2 of 60 pooled fly samples (3.3%), and 10 of 320 (3.1%)
water-trough sample sets (biofilm and water). No E. coli O157 were isolated from
300 rodents, 33 cats, 34 assorted wildlife, or 335 cattle feed samples.
Indistinguishable pulsed-field gel electrophoresis patterns of XbaI digested
chromosomal DNA and Shiga toxin types were observed for bovine and water-trough
isolates from two farms and for one equine and two bovine isolates from one farm.
PMID- 9638777
TI - Seroprevalences to Toxoplasma gondii in privately-owned dogs in Taiwan.
AB - The prevalences of IgG and IgM antibodies to Toxoplasma gondii in pet dogs in
Taiwan were measured by using both a kinetics-based enzyme-linked immunosorbent
assay and immunoblotting. A logistic regression model with five factors (sex,
age, weight, breed, domain) was analyzed. Pet dogs (n = 658) had seroprevalence
of 7.9%, and had IgG and IgM geometric mean titers of 1:50 and 1:31,
respectively. Older or heavier pet dogs had higher odds of seropositivity than
younger or lighter dogs. Also, mixed-breed dogs had higher odds of seropositivity
than pure-bred dogs.
PMID- 9638778
TI - Biological predictors for early clinical mastitis occurrence in Holstein cows
under field conditions in France.
AB - Individual risk factors for clinical mastitis within the first month of lactation
(early clinical mastitis, ECM) were analyzed in 695 Holstein multiparous cows
(561 ECM- and 134 ECM+) which were clinical mastitis-free during the previous
lactation. They belonged to 44 herds from the French Brittany region and were
surveyed for 4 years. Individual biological parameter levels during the last 2
months of gestation, production of the preceding lactation and calving conditions
and health were the available explanatory variables. The construction and
explanation model used multiple logistic regression run with herd as a fixed
effect. High precalving plasma ceruloplasmin oxidase (p < 0.01) and low glutamate
dehydrogenase (p < 0.05) activities, high 305-day previous-lactation milk yield
(p < 0.001) and milk protein content at the last milk-test day before drying-off
(p < 0.01) were the significant risk factors for ECM occurrence. Intensive
production and unsatisfactory dietary conditions (energy and antioxidants) would
increase ECM risk in the dairy cow. Further studies should be conducted to
determine if metabolic and/or genetic factors could explain the relationship
between ceruloplasmin and subsequent ECM occurrence.
PMID- 9638779
TI - Associations between milk-protein production and reproduction, health, and
culling.
AB - Associations between protein production and individual-cow reproductive
performance, health, and culling were investigated in a 2-year observational
study involving a convenience sample of 75 Ontario, 5 Alberta, and 3 Nova Scotia
dairy farms. Protein production was defined by 305-day lactation protein yields
and by estimated breeding values for protein yield. After controlling for the
level of milk production, herd, parity, breed, and season of calving, there were
no significant associations between either measure of protein production and days
open or days to first breeding. The only associations between protein production
and disease were small positive associations between the estimated breeding value
for protein yield and cystic ovaries and mean lactation somatic cell count. The
risk of culling, after controlling for the level of milk production, was
negatively associated with previous-lactation 305-day protein yield for parity
three animals only. The estimated breeding value for protein yield had a small
negative association with the overall risk of culling, although the associations
were not significant for individual lactations.
PMID- 9638780
TI - Measurement of digestive disorders in the piglet at weaning and related risk
factors.
AB - A cohort study was carried out in France about postweaning digestive disorders in
the piglet. One hundred and six farrow-to-finish farms were involved. In each of
them, a batch of contemporary piglets was considered. A total of 12,034 piglets
were ear-notched, evaluated during the suckling phase and weighed at weaning, at
14 and 28 days postweaning. Postweaning diarrhoea and mortality were recorded
daily. Data were collected about diet composition and feed intake, housing and
husbandry throughout the period. Weaning weight was 8.1 kg and weaning age was
27.2 days on average. Diarrhoea occurred in the pens after a 3-4-day latency
period. Prevalence was maximum around 7 to 9 days after weaning and remained high
until 21 days after weaning. Mortality was moderate (1.9%). Average daily gains
were 283 and 489 g for the two subsequent 14-day periods postweaning. Descriptive
multivariate methods indicated a strong pattern between diarrhoea, mortality and
growth. The main risk factors associated with the digestive disorders were
determined. The hygiene level at the reception of the piglets (cleanliness, level
of temperature), management and husbandry level (air quality, group size and
stocking procedure) were found to be important factors leading to risky or secure
profiles. In addition, the feed intake of the piglet during the first week
postweaning was strongly associated with the severity of the digestive disorders
over the whole 28-day postweaning period of observation. It is concluded that
prevention of postweaning digestive disorders could be based on the control of
zootechnical conditions.
PMID- 9638781
TI - Gender differences in outcomes among patients with cancer.
AB - This study examined gender differences in 162 female and 65 male patients with
cancer referred to home care. Data were collected before hospital discharge using
the Multidimensional Functional Assessment Questionnaire, the Karnofsky
Performance Status, and the Quality of Life-Cancer Scale. Controlling for age and
stage of disease, the results showed that men reported significantly more cancer
related impairments, more limitations in activity of daily living, and poorer
social resources than women. No gender differences were found in quality of life,
perceived emotional health, perceived physical health, performance status, and
comorbidity. Significant predictors of self-care activities were: for women
perceived physical health, Karnofsky Performance Status, and stage of disease
(58% variance explained); for men Karnofsky Performance Status and medication
taken (67% variance explained). Gender differences should be considered in
discharge planning to provide appropriate home care services for male and female
patients with cancer.
PMID- 9638782
TI - Reducing distress in cancer patients with an orientation program.
AB - The purpose of this study was to test a brief orientation program for reducing
anxiety, depressive symptoms, and overall distress in cancer patients at their
initial clinic visit. One hundred and fifty consecutively referred patients seen
in an oncology outpatient clinic were randomly assigned to an intervention or
usual care control group. The intervention group received a clinic tour, general
information about clinic operations, and a question and answer session with an
oncology counselor. Outcome measures included the State-Trait Anxiety Inventory
(STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic
Studies-Depression (CES-D) Scale, and an oncology clinic questionnaire which were
administered at the initial clinic visit and follow-up. There were no
statistically significant clinical or demographic differences between groups at
initial assessment. At follow-up, the intervention group had lower state anxiety,
lower overall distress, and fewer patients reporting depressive symptoms.
Patients in the intervention group demonstrated significantly more knowledge
about clinic operations and greater satisfaction with care. These data provide
evidence that anxiety, distress and depressive symptoms can be reduced with an
orientation program. This finding has particular relevance in the early stages of
diagnosis where patients may suffer symptoms of anxiety and depression.
PMID- 9638783
TI - A comparison of adjuvant psychological therapy and supportive counselling in
patients with cancer.
AB - This study compared the effectiveness of two psychological treatments in a group
of 57 patients with various types of cancer attending the Royal Marsden Hospital.
Patients referred for psychiatric assessment who met criteria for an abnormal
adjustment reaction were randomly allocated to either 8 weeks of Adjuvant
Psychological Therapy (APT), a problem-focused, cognitive behavioural treatment
programme, or 8 weeks of a comparison treatment of supportive counselling. At 8
weeks from the baseline assessment, APT had produced a significantly greater
change than the counselling intervention on fighting spirit, helplessness, coping
with cancer, anxiety, and self-defined problems. At 4 months from baseline, APT
had produced a significantly greater change than counselling on fighting spirit,
coping with cancer, anxiety and self defined problems. It is concluded that APT
produces greater change in anxiety, adjustment to cancer and use of coping
strategies than a non-directive, supportive intervention over an 8 week period of
treatment. This difference persists at follow up 4 months after baseline
assessment.
PMID- 9638784
TI - Spanish version of the Rotterdam Symptom Check List: cross-cultural adaptation
and preliminary validity in a sample of terminal cancer patients.
AB - We report on the process of adaptation into Spanish of the Rotterdam Symptom
Check List (RSCL). The original version was translated and back-translated by
professional bilingual translators. A quantitative rating method was used to
select the items to include in the final Spanish version. Validity (discriminant
and construction) and reliability were test in 118 terminal cancer patients. In
addition to the RSCL the Nottingham Health Profile (NHP) and the Karnofsky
Performance Status (KPS) were used. The RSCL showed different ratings on all
scales according to the functional level of the patients. The scales were
moderately to highly correlated with the NHP (from 0.48 to 0.71). Internal
consistency, measured by Cronbach's alpha coefficient ranged from 0.74 (physical)
to 0.90 (activity). Twenty-four hours test-retest intraclass correlation
coefficient ranged from 0.71 to 0.88. The results of this study suggest that the
Spanish version of the RSCL is conceptually equivalent to the original. More
research is needed to assess the responsiveness of the version before using it in
clinical trials.
PMID- 9638785
TI - Strategies of information disclosure to Chinese cancer patients in an Asian
community.
AB - There is little information available on strategies of information disclosure
used by doctors in the care of patients with cancer. This report focuses on the
style of disclosure used by doctors when giving diagnostic and prognostic
information to patients with cancer. Among 46% of 133 surgeons and
radiotherapists interviewed, disclosure of diagnosis involved a sudden approach
(information given outright at one sitting). Less commonly used (19%) was a
gradual disclosure style. Of the remainder who disclosed, more than half did so
through the family or left it to the family to tell the patient. Doctors'
specialty and patients' requests for prognostic information dictated disclosure
style most frequently. Single people were more likely to have information
disclosed to their families than were married people. While anecdotal accounts
indicate negative reactions on the part of patients are a major reason for
withholding such information, different disclosure style had little effect on
doctors' reports of patient reactions to the bad news. Doctors perceived 25% of
patients appeared to react 'with depression' but the remaining 75% appeared
'calm'. These results suggest patients are more likely to be told bad news
suddenly, and that doctors do not perceive that this impacts too negatively on
patients. The high levels of reported preference for information about cancer in
Hong Kong (Fielding and Hung, 1996) conflict with actual prevalence patterns. It
seems that commonly cited anecdotal reasons for withholding information from
cancer patients in Hong Kong are not sustained by the data produced in these
studies.
PMID- 9638786
TI - The quality and coping patterns of women's decision-making regarding breast
cancer surgery.
AB - This study addressed issues regarding the decision-making process used by women
who had mastectomy as their surgical treatment for breast cancer. The seven
criteria for quality decision-making and the conflict model proposed by Janis and
Mann (1977) were used as the study's conceptual framework along with the notion
by Simon (1957) of 'bounded rationality'. Four coping patterns emerged: vigilance
(actively searches for information and advice), satisficing (being satisfied,
chooses first solution that meets the desired objectives), complacency (accepts
advice without questions or fully comprehending), and defensive avoidance
(rationalises and avoids discussion and consideration of the problem). The
participants primarily left the decision for surgical treatment of breast cancer
to their surgeons using satisficing, complacency and defensive avoidance. When
the option of lumpectomy was offered to some of the participants (34%), they
rejected this treatment alternative using the coping patterns of satisfying and
defensive avoidance. Those women who were not offered lumpectomy (66%) did not
seek a rationale for not being given this alternative. The findings indicated
that the women's decision-making process was halted in Stage 2 of the criteria
for quality decision-making actively searched for and viewed a number of
alternatives. The study's findings are discussed in relation to improving the
quality of the decision-making process for women regarding their breast cancer
surgical treatment.
PMID- 9638787
TI - 'You don't want to lose your ovaries because you think 'I might become a man".
Women's perceptions of prophylactic surgery as a cancer risk management option.
AB - This preliminary study provides insight into the meaning of prophylactic surgery
as a risk management strategy for women who have a familial risk of breast or
ovarian cancer. Data were collected during observations of genetic consultations
and in semi-structured interviews with 41 women following their attendance at
genetic counselling. The option of prophylactic surgery was raised in 29
consultations and discussed in 35 of the post-clinic interviews. Fifteen women
said they would consider having an oophorectomy in the future and nine said they
would consider having a mastectomy. The implications of undergoing oophorectomy
and mastectomy were discussed during the post-clinic interviews. Prophylactic
surgery was described by the counsellees as providing individuals with a means to
(a) fulfil their obligations to other family members and (b) reduce risk and
contain their fear of cancer. The costs of this form of risk management, were
described as: (a) compromising social obligations; (b) upsetting the natural
balance of the body; (c) not offering protection from cancer; (d) operative and
post-operative complications; (e) the onset of menopause (f) the effects on body
image, gender and personal identity and (g) potential effects on sexual
relationships.
PMID- 9638788
TI - Digestive and metabolic adaptations of ruminants to undernutrition, and
consequences on reproduction.
AB - In response to undernutrition, short- (days) and medium-term (weeks) adaptations
are more pronounced for splanchnic organs than for other tissues. For the latter,
the long-term response involves a sequential mobilization (fat > muscle > bone)
with relative priorities differing among anatomical sites. Among chemical
components, the body lipids are extensively used (up to 80%) in underfed animals,
while the range of protein utilization is limited (up to 15-20%). The decrease in
energy expenditure during undernutrition is mostly due to a short- and medium
term decrease in feeding activity, and in the mass and activity of splanchnic
tissues. In the long-term, energy expenditure and tissue masses decrease
concomitantly, but there does not appear to be a significant decrease in
expenditure per unit tissue weight. Nitrogen losses decrease in response to
decline in nitrogen fluxes and also due to sparing by renal activities and
sometimes by urea recycling. However, ruminants do not seem to be able to
compensate for a low level of intake (below maintenance) by an increase in
digestive efficiency. Numerous hormones (insulin, growth hormone, insulin-like
growth factor I, catecholamines, thyroid hormones, cortisol, leptin, etc.) are
involved in the changes during undernutrition of nutrient fluxes between tissues,
either through control of synthesis and/or degradation in peripheral tissues
(adipose tissue and muscle), or through hepatic conversions of substrates
(gluconeogenesis, ureagenesis and ketogenesis), in order to maintain the
constancy of the internal environment (homeostasis) and/or to sustain productive
functions (teleophoresis). However, reproductive process may be blocked in
underfed animals.
PMID- 9638789
TI - Ubiquitin-proteasome-dependent proteolysis in skeletal muscle.
AB - The ubiquitin-proteasome proteolytic pathway has recently been reported to be of
major importance in the breakdown of skeletal muscle proteins. The first step in
this pathway is the covalent attachment of polyubiquitin chains to the targeted
protein. Polyubiquitylated proteins are then recognized and degraded by the 26S
proteasome complex. In this review, we critically analyse recent findings in the
regulation of this pathway, both in animal models of muscle wasting and in some
human diseases. The identification of regulatory steps of ubiquitin conjugation
to protein substrates and/or of the proteolytic activities of the proteasome
should lead to new concepts that can be used to manipulate muscle protein mass.
Such concepts are essential for the development of anti-cachectic therapies for
many clinical situations.
PMID- 9638790
TI - Effect of training on muscle strength and motor function in the elderly.
AB - Overall muscle strength and mass decline 30-50% between the ages of 30 and 80.
The loss of muscle mass, the so called sarcopenia, accounts for most of the
observed loss of strength. A reduced specific muscle force has also been observed
but its contribution to the decrease in strength with age remains unclear. The
loss of muscle tissue is due to a decrease in the number of muscle fibres and
atrophy of the type II muscle fibres. The declining strength reduces the capacity
to carry out basic activities of daily life and puts people at risk for falls and
dependence. Resistive strength training greatly increases muscle strength even in
very old people. It produces muscle fibre hypertrophy and improves neural factors
involved in force production. The recovered strength in turn enhances the
physical performance and allows a more active and independent life towards the
end of the life span.
PMID- 9638791
TI - Alteration in nutritional status and diaphragm muscle function.
AB - Diet-induced undernutrition causes deleterious changes in the structure and
function of the diaphragm muscle. Diseases associated with somatic washing cause
atrophy of the respiratory muscles. In cachectic subjects, the diaphragm muscle
mass and thickness are reduced in proportion to the reduction in body weight. In
addition, respiratory muscle strength and endurance are reduced more dramatically
than the weight loss. This finding suggests that malnutrition induces a reduction
in muscular mass which is associated with a decrease in contractility.
Diaphragmatic weakness may increase the risk of respiratory failure in patients
with chronic obstructive pulmonary disease (COPD). The primary goal of a
successful nutritional programme is to improve the diaphragm strength by
correcting the mineral, electrolyte and energetic disturbances at the muscular
level, the latter being responsible for the decreased contractability associated
with malnutrition.
PMID- 9638792
TI - Duchenne muscular dystrophy: a model for studying the contribution of muscle to
energy and protein metabolism.
AB - Duchenne muscular dystrophy (DMD) is associated with a dramatic muscle mass loss.
We hypothesized that DMD would be associated with significant changes in both
energy and protein metabolism. We studied the resting energy expenditure (REE) in
DMD and control children using indirect calorimetry, and their protein metabolism
using an intravenous infusion of leucine and glutamine labeled with stable
isotopes. In spite of a 75% muscle mass loss in the DMD children, the REE only
decreased by 10%. DMD was associated with increased leucine oxidation but neither
protein degradation nor protein synthesis were different from that of the
controls. In contrast, whole body turnover of glutamine, an amino acid mainly
synthesized in the muscle, was significantly decreased. These studies emphasized
the quantitatively poor contribution of muscle to energy and protein metabolism
in children. The qualitative impact of muscle mass loss on amino acid metabolism
(glutamine) offers a fascinating field of research for the next few years and has
therapeutic potential.
PMID- 9638793
TI - IV perflubron emulsion versus autologous transfusion in severe normovolemic
anemia: effects on left ventricular perfusion and function.
AB - Intact cardiac compensatory mechanisms are necessary to maintain adequate tissue
oxygenation during acute normovolemic hemodilution (ANH). Left ventricular (LV)
perfusion, oxygenation and function were analyzed in an experimental whole-body
model of profound ANH (Hct 9%) and effectiveness of a perfluorocarbon-based
oxygen carrier in maintaining myocardial oxygenation and function was evaluated.
A total of 22 anesthetized dogs were hemodiluted to Hct 20% followed by a
simulated, controlled blood-loss phase in which dogs were randomized to either:
(1) 1:1 exchange of lost blood with autologous red blood cells (RBC-group), (2)
1:1 exchange with a colloid (control-group) and (3) 1:1 exchange with a colloid
after a single dose of 1.8 g/kg BW perflubron i.v. (PFC-group). Myocardial oxygen
delivery and consumption as well as endocardial perfusion were determined using
radioactive microspheres. LV myocardial contractility (LV MC) was assessed from:
(1) the relationship between maximum rate of LV pressure increase (LVdp/dtmax)
and LV enddiastolic volume (LVEDV) and (2) analysis of the LV endsystolic
pressure volume relationship (ESPVR). LV diastolic properties were reflected by
(1) minimum rate of LV pressure increase (LVdp/dtmin), (2) slope and intercept of
the enddiastolic pressure-volume relationship (EDPVR) and (3) the time-constant
of isovolumic LV pressure decline "tau 1/2". Full sets of LV MC data were
obtained from 18 dogs (n = 6 per group). LV MC (LVdp/dtmax-LVEDV relation)
increased after perflubron administration. At the lowest Hct level, all
parameters reflecting LV MC as well as LVdp/dtmin were significantly higher in
the PFC-group than in the control-group. After profound normovolemic hemodilution
(Hct 9%) superiority of LV MC and LV diastolic properties was found, when
myocardial oxygenation was supported by i.v. perflubron emulsion, a temporary O2
carrier.
PMID- 9638794
TI - Type V phosphodiesterase inhibition modulates endogenous immunoreactivities of
endothelin-1 and endothelial nitric oxide synthase in pulmonary arteries in rats
with monocrotaline-induced pulmonary hypertension.
AB - We evaluated the effects of oral administration of E4021 (100 mg/kg/day), a type
V phosphodiesterase inhibitor, on immunoreactivities of endothelin-1, endothelin
receptors, and nitric oxide synthases in pulmonary arteries in a rat model of
pulmonary hypertension. Immunoreactivities of endothelin-1 and endothelial nitric
oxide synthase were observed significantly less frequently, together with
significant reduction of right ventricular overload and medial thickening in rats
treated with E4021 than in the control with monocrotaline on day 28. The levels
of plasma endothelin-1 and serum nitrite and nitrate were significantly lower in
rats that received E4021 than in the control with monocrotaline. Oral
administration of E4021 modulates endogenous immunoreactivities of endothelin-1
and endothelial nitric oxide synthase with the improvement or right ventricular
overload and medial thickening.
PMID- 9638795
TI - Liver bilirubin UDP-glucuronosyltransferase activity in chronic nonhemolytic
unconjugated hyperbilirubinemia of adults.
AB - Ten adult patients with chronic nonhemolytic unconjugated (indirect)
hyperbilirubinemia were analyzed by determining bilirubin uridine diphosphate
glucuronosyltransferase activity according to a more physiological and sensitive
method (9 control cases, 0.457 +/- 0.163 nmole/mg protein/min). There was no
overlap of the enzyme activities of 2 cases with Crigler-Najjar syndrome (type
II) (0.006 nmole/mg protein/min on average) and 6 cases with Gilbert's syndrome
(0.051 +/- 0.016 nmole/mg protein/min). The enzyme activities in 2 patients with
post-hepatitic hyperbilirubinemia were within the normal range. A new
classification of nonhemolytic unconjugated hyperbilirubinemia in adults is
proposed according to the results of this enzyme activity and the recent data on
the gene mutation of this enzyme.
PMID- 9638796
TI - The systemic vasodilatory action of protamine: is it inhibited or mediated by
heparin?
AB - The administration of protamine to neutralize the circulating heparin is common
practice in cardiovascular surgery. The use of this drug is sometimes associated
with hemodynamic alterations of varying degree and intensity (systemic
hypotension, pulmonary hypertension and even cardiogenic shock). An intrinsic
action of protamine has been suggested to be the cause of these vascular
reactions. This action is blocked when protamine forms a complex with heparin,
although in other cases it appears that the heparin-protamine complex is the
factor responsible for these hemodynamic alterations. The aim of this
experimental study was to characterize the vasodilatory action of protamine on
the systemic circulation, determining whether or not it is dose-dependent; to
analyze the role of endothelium; and to evaluate whether this vasodilatory effect
is modified by the presence of heparin. MATERIALS AND METHODS: The abdominal
aorta was dissected from eight New Zealand rabbits and then sectioned into
vascular rings for study in an organ chamber. Mechanical disruption of
endothelium was performed on some rings (n = 14). Once submaximal contraction was
reached (ClK 80 mM), protamine sulfate with a final concentration in the organ
chamber of 80-400 micrograms/ml was added to one of the groups (n = 12). In the
second group (n = 12), equal concentrations of protamine were tested in the
presence of heparin at a final concentration of 100 U/ml. RESULTS: The mean
vasodilatation reached in the group of rings exposed only to protamine was 95.4
+/- 1.5% with respect to the submaximal contraction induced with ClK. In the
second study group, the rings were exposed to protamine at equally increasing
concentrations (80-400 micrograms/ml) but with the presence of heparin in the
organ chamber. The mean vasodilatation in this group was 90 +/- 1.5. No
statistically significant differences in vasodilatation were found between this
group and the protamine without heparin group. On the other hand, in the
endothelium-denuded rings (n = 14) exposed to isolated protamine and to protamine
heparin, no vasodilatory response was observed. CONCLUSION: Our results show that
the administration in vitro of protamine induces endothelium-dependent
vasodilatation of the systemic circulation. Likewise, this relaxing effect
mediated through endothelium is not blocked when protamine forms a complex with
heparin in comparable concentrations of both drugs. Based on these preliminary
findings, we believe that in high-risk patients the prevention of systemic
vasodilatation and cardiovascular collapse produced by protamine should move
towards the use of other substances that can neutralize the anticoagulant effect
of heparin or towards pre-medication guidelines that prevent these secondary
effects in the case of protamine administration.
PMID- 9638797
TI - Prevention of intestinal adhesions after laparotomy in a rat model--a randomized
prospective study.
AB - We prospectively studied the effect of a foam composite containing glycerin,
propylene glycol, polyol, stearine, stearate and silicone oil, which is known to
form a temporary barrier layer when applied to epithelial surface, on adhesion
prevention in rats. The small intestine abrasion model was used for creation of
adhesions. Sixty male Sabra rats of a mean weight of 295 +/- 23 g were randomly
assigned into four groups: group 1 (n = 20) underwent laparotomy and abrasion;
group 2 (n = 20) underwent laparotomy, abrasion and intraperitoneal instillation
of the foam composite; group 3 (n = 10) underwent laparotomy with abrasion and a
second laparotomy with adhesiolysis 2 weeks later; and group 4 (n = 10), was
treated in the same way as group 3 but during the second laparotomy the foam
composite was instilled intraperitoneally. All animals were relaparotomized 2
weeks (groups 1 and 2) and 4 weeks (groups 3 and 4) after the initial laparotomy
for adhesion scoring performed by a blinded independent investigator using the
standard 0-3 adhesion grading score. Representative specimens of small intestine
and liver from animals in groups 2 and 4 were analyzed. A significantly lower
mean adhesion score was noted in group 2 (1.15 +/- 0.3) compared with that of
group 1 (2.65 +/- 0.1) or group 3 (2.60 +/- 0.1) (P < 0.01). Group 4 had a
significantly lower score (1.4 +/- 0.3) than group 3 or group 1 (P < 0.05). There
was no significant difference in the mean adhesion score between groups 1 and 3.
Histological examination revealed no evidence of residual foam composite or
adverse reaction to its use in the intestine and liver. The foam composite tested
may reduce the severity of intestinal adhesions after laparotomy and may also
reduce the severity of recurrent adhesions after adhesiolysis. Intraperitoneal
use of this composite is safe in rats. The exact mechanism of action is unclear
but may be related to the formation of a temporary microlayer that coats the
injured surface of the intestine and facilitates healing without adhesion
formation. Further investigation is needed to evaluate its full potential.
PMID- 9638798
TI - Resolving the genetics of resistance to infectious diseases.
AB - The genetics of resistance to disease is an area of great interest in
agriculturally important plant and animal species. Selective breeding for
resistance to pathogens in plants, animals and insects has demonstrated that
resistance and susceptibility to pathogens are controlled by both genetic and
environmental factors. The immune loci causally involved in susceptibility and
resistance to disease are currently unknown. However, novel enabling molecular
technologies promise to assist in unravelling the genetics of the host response
to infectious diseases in new ways, and ultimately to improve seed stock
genetics.
PMID- 9638799
TI - Constitutional and non-specific immunity to infection.
AB - Most immunologists focus on elaborate non-specific and antigen-specific factors
of reactive immunity produced by the vertebrate lymphoid system. Modern
principles of immunogenic prophylaxis and therapy are based solely on the use of
these agents. There is, however, a more effective system of specific resistance
which is shared by all forms of life: hereditary constitutional immunity to
infection and invasion. An explosive growth in knowledge of the constitutional
immunogenic system has occurred during the past two decades. The author
illustrates the nature and importance of constitutional immunity, using examples
from genetics and molecular biology. Special attention is given to testing for
genetic susceptibility to infection and genetic engineering of resistance.
PMID- 9638800
TI - Immunoglobulin diversity, B-cell and antibody repertoire development in large
farm animals.
AB - The B-cell lineage, the antibodies produced by these cells and the
diversification of the antibody repertoire are essential for the health and
survival of all mammals. Cattle, sheep, swine and horses, unlike rodents and
primates, develop their antibody repertoire from a relatively small number of VH
(variable heavy) genes of one or several families and cattle, sheep and horses
use almost exclusively lambda-light chains. These large farm animals appear to
use templated mutation (gene conversion) in addition to untemplated (point)
mutation in repertoire development; this may occur predominantly in the ileal
Peyer's patches. Whether B-cell lymphogenesis is continuous throughout life--as
in rodents and primates--or whether B cells are largely of the B-1 lineage and
develop only in foetal and neonatal life, is uncertain. The fact that
immunoglobulin D (IgD) is totally absent from swine and ruminants may be
significant, as IgD is expressed weakly on rodent B-1 cells. Information on IgG
subclass diversity in large farm animals is incomplete, except for sheep and
cattle, and no information is available for any large farm animal to show whether
T helper 1 (Th1) and Th2 responses correlate with the expression of any subclass
antibody response, as is the case in rodents. All large farm animals exclusively
use the mammary gland to transfer immunity to offspring, although the receptor
involved in the transport of IgG into colostrum and milk has not been
characterised. Efforts to standardise the nomenclature and measurements of
antibodies and immunoglobulins in large farm animals are discussed, and a
proposal currently under review concerning the standardisation of the
nomenclature for bovine immunoglobulins is presented as a model.
PMID- 9638801
TI - Antigen-specific immune response of porcine T lymphocytes to various pathogens.
AB - The importance of swine in agriculture has resulted in a substantial increase in
research efforts on the swine immune system during the past few years. A better
knowledge of the porcine immune system is required before improved vaccination
strategies, the design of more efficient vaccines and breeding for disease
resistance will be able to contribute to a reduction in the extensive economic
losses caused by the disabling effects of viral, bacterial and parasitic
infections. T lymphocytes play a central role in the antigen-specific immune
response to the various pathogens. To detect and characterise porcine T
lymphocytes, monoclonal antibodies (mAbs) were raised against different leucocyte
differentiation antigens and classified for specificity in two international
workshops. These mAbs have enabled detailed studies to be made on specific cell
populations involved in the porcine immune response to pathogens, on T
lymphocytes and on the peculiarities of porcine T lymphocyte sub-populations:
extra-thymic CD4+CD8+ T lymphocytes and a substantial proportion of CD2-TCR gamma
delta+ T cells. Furthermore, these reagents and the increased knowledge of the
immune system have allowed studies of the interactions of T lymphocyte sub
populations with regard to different pathogens and the role which these play in
infections.
PMID- 9638802
TI - Cytokines orchestrating the immune response.
AB - The author summarises the current knowledge of the major immune cytokines, their
receptors and functions, and illustrates the pivotal role of cytokines in
regulating immune responses. As researchers explore the factors which influence
the genetics of disease resistance in livestock and poultry, alleles associated
with differences in the expression of, and responsiveness to, cytokines will
inevitably be defined. Variations in cytokine receptors, as well as in
sensitivity to the rapidly expanding array of cytokine agonists and antagonists,
will also be identified. These differences influence not only disease resistance
but also potential disease pathology and speed of recovery from infection. The
author concludes with a discussion of some uses of cytokines in clinical
practice. This area is the subject of active exploration with clinical trials in
many species, addressing issues such as immune system stimulation and disease
treatment with cytokine proteins. As veterinarians use such new biotherapeutics,
the issue of genetic control of responses to deliberate cytokine stimulation will
become important to producers.
PMID- 9638803
TI - Porcine major histocompatibility complex.
AB - The major histocompatibility complex in swine (swine leucocyte antigen: SLA) is
located on chromosome 7 with the class I and class III regions separated by the
centromere from the class II region. The overall molecular organisation of the
class I and III regions is well known, but further research is needed to
establish that of the class II region. Approximately sixty genes have been
characterised to date, including ten tightly packed SLA class I sequences. The
exact number of functional polymorphic class I genes, as defined by serology,
probably varies from one to four, depending on the haplotype. At least two other
distantly class I-related gene families exist. The numerous and significant
associations reported between SLA haplotypes and physiological traits are
described. These traits include immune responsiveness to a variety of microbes
and metazoan parasites, and male and female production and reproduction
performance. The results obtained suggest that selection for specific SLA
haplotypes may assist in the improvement of porcine production.
PMID- 9638804
TI - The major histocompatibility complex of ruminants.
AB - Studies of the major histocompatibility complex (MHC) of cattle over the past
twenty years have revealed a reasonably detailed picture of the genetic
organisation and function of the genes within this genetic system. Serological
and biochemical analysis of lymphocyte cell surface antigens provided the first
evidence for highly polymorphic MHC genes in cattle and other ruminant species.
The MHC of cattle was thus named the bovine leucocyte antigen (BoLA) system.
During the past 10 years, tools of molecular biology have been used to
characterise the number of MHC genes, their sequence and fine structure in a
number of ruminant species. Although individual MHC genes were found to have
clear orthologues among ruminants and other mammalian species, the MHC of cattle,
and probably that of sheep and goats, has a unique genetic organisation. Cattle
have a class II gene cluster (class IIb region) which is physically distant from
all the other MHC genes on the same chromosome. Moreover, genes involved in
antigen processing, such as the proteosome subunit locus LMP2, are also found in
the class IIb region, demonstrating that these genes need not be in close
proximity to other MHC genes to function normally. The MHC class I and class II
gene products of ruminants present processed peptides to T lymphocytes which
mediate helper and cytotoxic functions. Identification of peptide binding motifs
of cattle MHC class I molecules indicates that ruminant MHC molecules function in
a similar manner to those of mice and humans. These functional studies provide a
firm molecular basis for a number of well-documented associations with infectious
diseases, although a detailed understanding of the immunogenetic mechanisms
underlying these associations has yet to be elucidated.
PMID- 9638805
TI - The major histocompatibility complex in fish.
AB - The first major histocompatibility complex (MHC) molecule in fish was identified
in 1990 using a polymerase chain reaction strategy with degenerate primers
(thereby avoiding the problem of low sequence similarity between higher
vertebrates and fish). Since that time, MHC in fish has attracted much attention,
partly due to evolutionary aspects and partly because of the potential practical
consequences for future fish breeding. Knowledge of the MHC molecules in fish has
thus been growing extremely rapidly. All current data point to a functional MHC
system in fish. There seem to be many loci and many alleles for both classes of
MHC molecules, but a lack of knowledge about functional loci versus pseudogenes
and non-classical loci is making it difficult at present to establish the exact
number found within each species. Fish create a few surprises, such as the lack
of a link between class I and class II regions in at least two teleost species.
Data on other molecules which are physically or functionally linked to the MHC
genes are currently emerging. To date, no studies have established the functional
implications of the MHC molecules in fish but, considering the molecular data
available, such an achievement will undoubtedly occur soon. Fish may well offer a
unique opportunity for identifying correlations of MHC with resistance or
susceptibility to diseases.
PMID- 9638806
TI - The chicken major histocompatibility complex and disease.
AB - The chicken major histocompatibility complex (MHC), or B complex, consists of
several clusters of highly polymorphic genes, some of which are associated with
disease resistance. The class I and class II antigens resemble their mammalian
counterparts in the encoded protein structure. The class IV region encodes the B
blood group antigens, which are readily identified by serological blood-typing.
The class III region appears to be divided in chickens, with some elements that
are MHC-linked and others that map elsewhere. In addition the Rfp-Y system, which
bears a strong similarity to the MHC, maps to the opposite side of the nucleolar
organiser region on the same microchromosome as the MHC. Each class of MHC genes
is a potential candidate for a role in disease resistance. The MHC genes show
associations with response to diseases as diverse as virally induced neoplasia,
bacterial, parasitic and auto-immune diseases.
PMID- 9638807
TI - Genetic resistance to parasitic infection.
AB - The ability of animals to resist infections with parasites is genetically
determined and therefore variable between individuals or breeds of a given host
species. Such variation may involve innate (non-immunological) and acquired
(immunologically mediated) resistance mechanisms, and is determined by both major
histocompatibility complex (MHC)-linked and non-MHC genes. Resistance is
inherited as a dominant trait, with heritability often exceeding 0.3. Genetic
variation can be exploited to improve the capacity of domestic animals to resist
parasitic infection. Methods to achieve this exploitation are discussed in
relation to gastrointestinal nematode infections in sheep.
PMID- 9638808
TI - Trypanotolerance, an option for sustainable livestock production in areas at risk
from trypanosomosis.
AB - Trypanosomosis is one of the major constraints on animal production in areas of
Africa which have the greatest potential for significant increases in domestic
livestock populations and livestock productivity. While the eradication of
trypanosomosis from the entire continent is an unrealistic goal, considerable
effort has been invested in the control of this disease through the use of
trypanocidal drugs, management of the vector and exploitation of the genetic
resistance exhibited by indigenous breeds. There is little hope that a
conventional, anti-infection vaccine will be produced in the near future. Drug
resistance is developing faster than generally thought. The control of the tsetse
fly has been attempted over many decades. The decreasing efficacy of available
trypanocidal drugs and the difficulties of sustaining tsetse control increase the
imperative need to enhance trypanotolerance through selective breeding, either
within breeds or through cross-breeding. Trypanotolerance has been defined as the
relative capacity of an animal to control the development of the parasites and to
limit their pathological effects, the most prominent of which is anaemia. A major
constraint on selection for trypanotolerance in cattle, for both within-breed and
cross-breeding programmes, has been the absence of practical reliable markers of
resistance or susceptibility. Distinct humoral immune response to trypanosome
infection is the major feature of bovine trypanotolerance. The role that these
responses play in the control of infection or disease is being addressed by
ongoing research, but remains a matter of speculation at present. Results in
recent years have shown that packed cell volume (PCV) in particular and
parasitaemia, the two principal indicators of trypanotolerance, are strongly
correlated to animal performance. However, although direct effects of trypanosome
infections on PCV and growth are obvious, more sensitive diagnostic methods for
reflecting parasite control are required so that individual animals can be
categorised reliably for their parasite control capability. One key finding is
the major contribution made by each of the indicators evaluated to the overall
trypanotolerance variance. Preliminary genetic parameters for PCV provide
evidence that trypanotolerance is not only a breed characteristic but is also a
heritable trait within the N'Dama population; this brings new opportunities for
improved productivity through selection for trypanotolerance. More reliable
estimation of genetic parameters of the indicators may well show that these
parameters must be handled simultaneously for optimal progress. This would
require diagnostics for assessing parasite control capability that identify
trypanosome species more accurately, especially in mixed infections. A major
advantage of trypanotolerant livestock, particularly N'Dama cattle, is the
resistance or adaptation of this breed to many of the important pathogenes which
prevail in the sub-humid and humid tropics. Research on practical indicators of
resistance to these conditions will be required to establish relevant integrated
strategies based on disease-resistant livestock. Selective breeding will require
the integration of the traits that farmers hold important for their production
systems.
PMID- 9638809
TI - Murine leishmaniosis: a paradigm for the importance of T helper 1 and T helper 2
cells.
AB - The murine model of leishmaniosis is a prototypic example for the critical role
played by T helper cells in immunity to pathogens. Cytokines, such as interleukin
12 and interleukin-4, are the major regulatory factors for differentiation of
naive T helper cells into T helper 1 and T helper 2 cells, respectively. T helper
1 cells, which are cellular immune mechanisms involving gamma interferon
production, are associated with protection against murine leishmaniosis. Loss of
T helper 1 activity (i.e., reduced gamma interferon production and lack of
macrophage activation) leads to a fatal progressive course of murine
leishmaniosis. Knowledge of the murine model of leishmaniosis is now contributing
to studies of infectious diseases in humans, livestock and companion animals.
Greater insight into the pathogenesis, diagnosis and therapy of infectious
diseases will be gained from the analysis of cytokine-dependent regulation of T
helper responses during infection. In particular, the development of prophylactic
and therapeutic vaccines will benefit significantly from these studies.
PMID- 9638810
TI - The use of vaccines and genetically resistant animals in tick control.
AB - The control of ticks and diseases transmitted by ticks is extremely difficult.
Application of acaricides is the most common prophylactic and therapeutic control
measure against these ectoparasites. The selection of tick strains which are
resistant to these products, the appearance of chemical residues in milk and
meat, and environmental pollution resulting from the use of acaricides pose real
problems. This article deals with aspects of current work on the alternative
control of ticks and places special emphasis on the development of vaccines and
the utilisation of genetically resistant animals.
PMID- 9638811
TI - Genetic resistance to bacterial diseases of animals.
AB - Despite traditional disease control measures, losses attributable to infectious
diseases continue to impede the livestock industries. An alternative approach to
this problem is genetic disease resistance involving both immune and non-immune
mechanisms, which is the inherent capacity of a previously unexposed animal to
resist disease when challenged by pathogens. Although the nurturing environment
influences variability in disease expression, natural resistance has been found
to be inheritable and is transmitted from parent to offspring. Thus, an
alternative approach to enhancing animal health management systems is to increase
the overall level of genetic resistance at herd and population levels by using
selective breeding programmes. The purpose of this review is to bring
veterinarians, regulatory officials, industry representatives and animal
technicians up to date with the principles and applications of genetic resistance
as an adjunct to traditional interventions to control bacterial diseases of
livestock. Although genetic resistance to bacterial diseases is often regulated
by multiple genes controlling different processes of the host-pathogen
interaction, the genetics of natural resistance is being unravelled increasingly
by identification and characterisation of candidate genes, microsatellite markers
and comparative gene mapping, to develop more practical methods of application.
PMID- 9638812
TI - Mx proteins: mediators of innate resistance to RNA viruses.
AB - Mx proteins are interferon-induced members of the dynamin superfamily of large
guanosine triphosphatases. These proteins have attracted attention because some
display antiviral activity against pathogenic RNA viruses, for example against
members of the orthomyxovirus (influenzavirus) family or the bunyavirus family.
Transfected cells and transgenic mice expressing Mx proteins are highly resistant
to Mx-sensitive viruses, demonstrating that Mx proteins are powerful antiviral
agents. In humans, synthesis of MxA is observed during self-limiting viral
infections and may thus promote recovery from disease.
PMID- 9638813
TI - Genetic control of host resistance to flavivirus infection in animals.
AB - Flaviviruses are small, enveloped RNA viruses which are generally transmitted by
arthropods to animals and man. Although flaviviruses cause important diseases in
domestic animals and man, flaviviral infection of animals which constitute the
normal vertebrate reservoir may be mild or sub-clinical, which suggests that some
adaptation between virus and host may have occurred. While this possibility is
difficult to study in wild animals, extensive studies using laboratory mice have
demonstrated the existence of innate, flavivirus-specific resistance. Resistance
is heritable and is attributable to the gene Flvr, which is located on chromosome
5 in this species. The mechanism of resistance is at present unknown, but acts
early and limits the replication of flaviviruses in cells. While some evidence
supports a role for Flvr in enhancing the production of defective interfering
virus, thereby restricting the production of infectious virus, other reports
suggest that Flvr interferes with either virus RNA replication or RNA packaging.
Recent research suggests that cytoplasmic proteins bind to the viral replication
complex and that allelic forms of these proteins in resistant mice may restrict
the production of infectious progeny. Apparent resistance to flaviviruses has
been described in other vertebrates, although it remains to be seen if this is
attributable to a homologue of Flvr. Nonetheless, knowledge gained of the
characteristics and function of Flvr in mice should be applicable to other host
species, and improvement of resistance to flaviviral infection in domestic
animals by selective breeding or gene technology may ultimately be possible.
PMID- 9638814
TI - Genetic resistance to avian viruses.
AB - Viral infections of poultry can be catastrophic in terms of both welfare and
economics, and although vaccines have been very successful in combating these
diseases, new forms of viruses have evolved which present increasing difficulties
for vaccine control. Differences in genetic susceptibility are known to exist for
many of the major viral pathogens of poultry. Consequently, an increase in the
level of genetic resistance provides a possible means of enhancing protection of
flocks. This is particularly feasible where specific resistance genes have been
identified, as in the case of avian leukosis and Marek's disease, and the
development of genetic maps of the chicken has offered new possibilities for the
identification of further resistance genes. It has also become clear that there
are genetic differences in the response to live attenuated vaccine viruses, and
new possibilities exist to manipulate the genetics of host flocks so that the
effect of vaccination can be optimised.
PMID- 9638815
TI - Myxoma virus in rabbits.
AB - Myxoma virus in European rabbits (Oryctolagus cuniculus) is one of the best
documented examples of host-virus co-evolution. In the natural hosts (Sylvilagus
brasiliensis or S. bachmani rabbits in the Americas), myxoma virus causes a
benign cutaneous fibroma. In European rabbits, however, myxoma virus causes the
fulminant disease, myxomatosis. When introduced into wild European rabbit
populations in Australia, Europe and Great Britain, the virus was initially
highly lethal, killing in excess of 99% of infected rabbits. Development of
resistance was encouraged by the emergence of attenuated virus strains which
allowed the survival of moderately resistant rabbits. This may have occurred more
rapidly in hot climates, as high ambient temperatures increase the survival rate
of infected rabbits. Resistant rabbits are less effective transmitters of the
virus and this may encourage the emergence of more virulent virus strains. Little
is known of the mechanism of resistance. There have been suggestions of non
genetic resistance. However, these are yet to be confirmed experimentally.
PMID- 9638816
TI - Fv1, the mouse retrovirus resistance gene.
AB - A number of genes which affect the susceptibility of mice to infection by
retroviruses have been described. One of the most interesting of these genes is
Fv1 (Friend virus susceptibility 1), which acts at a stage in the retroviral life
cycle following virus entry into the cell but prior to integration and formation
of proviral structures. A detailed understanding of the mode of action of Fv1
might be expected to shed fresh light on early steps of the retroviral
replication, although progress has been slow in this area due to uncertainty
about the nature of the Fv1 gene. The recent cloning of Fv1 by a positional
approach fills this gap in current knowledge. Fv1 appears to be derived from a
fragment of a retroviral genome, an observation that may suggest novel approaches
to the control of retroviral replication.
PMID- 9638817
TI - The use of transgenic mice in the investigation of transmissible spongiform
encephalopathies.
AB - The prion, the transmissible agent that causes spongiform encephalopathies such
as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, is
believed to be devoid of nucleic acid and to be identical to PrPSc (prion
protein: scrapie form), a modified form of the normal host protein PrPC (prion
protein: cellular form) which is encoded by the single copy gene Prnp. The
'protein only' hypothesis proposes that PrPSc, when introduced into a normal
host, causes the conversion of PrPC into PrPSc; it therefore predicts that an
animal devoid of PrPC should be resistant to prion diseases. The authors
generated homozygous Prnp(o/o) ('PrP knockout') mice and showed that, after
inoculation with prions, these mice remained free from scrapie for at least two
years while wild-type controls all died within six months. There was no
propagation of prions in the Prnp(o/o) animals. Surprisingly, heterozygous
Prnp(o/+) mice, which express PrPC at about half the normal level, also showed
enhanced resistance to scrapie despite high levels of infectious agent and PrPSc
in the brain at an early stage. After introduction of murine PrP transgenes,
Prnp(o/o) mice became highly susceptible to mouse--but not to hamster--prions,
while the insertion of Syrian hamster PrP transgenes rendered the mice
susceptible to hamster prions but much less susceptible to mouse prions. These
complementation experiments enabled the application of reverse genetics. The
authors prepared animals transgenic for genes encoding PrP with amino terminal
deletions of various lengths and found that PrP that lacks 48 amino proximal
amino acids (which comprise four of the five octa repeats of PrP) is still
biologically active.
PMID- 9638818
TI - Conventional breeding programmes and genetic resistance to animal diseases.
AB - The power of selection is illustrated by the increase in the average annual yield
of dairy cows in Sweden in kg fat-corrected milk from 2,500 kg in the year 1900
to 8,200 kg in 1997. More than a half of this improvement has a genetic origin.
The breeding goal for dairy cattle has successively been broadened to cover
traits other than production. The prerequisites for a successful breeding
programme and the consequences of the process are presented in this article. The
dramatic improvement of the reproduction techniques and statistical tools for
genetic evaluation of breeding stock and selection, which have occurred during
the last 50 years, is also discussed. The factors which affect the genetic gain
are described in detail to demonstrate the possibility of making genetic gains in
traits reflecting disease resistance. The Swedish procedure of disease recording
and the procedures for genetic evaluation of fitness traits, such as disease
resistance and female fertility, are described. The existence and consequences of
negative genetic correlations between production and fitness traits are dealt
with, as is the procedure for multi-trait selection. An illustration of methods
for performing multi-trait selection in real life, and the consequences of such
selection in an envisaged Nordic selection scheme, are given. Finally, the
authors review the present genetic trends for fitness traits of dairy cows in
Sweden.
PMID- 9638819
TI - Biological principles of heredity of and resistance to disease.
AB - Understanding the biological principles of disease heredity and resistance to
disease is a prerequisite for the incorporation of these factors into multi-trait
breeding programmes. Mutations represent an evolutionary aspect of disease. The
author reviews patterns of Mendelian inheritance and possible causes of non
Mendelian inheritance, such as multifactorial inheritance, expansion of
trinucleotide repeats, mitochondiral inheritance and genomic imprinting, in
relation to diseases of domestic animals. Host-pathogen interactions underlie
genetic variability in resistance to disease. Infectious pathogens endowed with a
high potential for evolutionary change use this potential to evade various host
defence mechanisms. This interaction may have a competitive or co-evolutionary
character. The host immune system copes with the variability of pathogens by
using the potential of genetic diversity of lymphocytes in immunoglobulin, T-cell
receptor and major histocompatibility complex genes. Possible mechanisms for
maintenance of this diversity are discussed in the context of selection for
disease resistance.
PMID- 9638820
TI - Breeding for disease resistance in Merino sheep in Australia.
AB - Breeding for disease resistance in Merino sheep in Australia has attracted
considerable research and development attention. Increased labour costs, the
reduced efficacy of common anthelmintics and insecticides, consumer demand for
products which are free of chemicals and the poor prognosis of alternative long
term control strategies are all forcing sheep breeders to contemplate the best
animal health options available, including selective breeding for resistance. The
three major diseases which affect sheep production include gastrointestinal
nematode parasites, flystrike (cutaneous myiasis) and footrot. Genetic
improvement has been shown to be feasible in all these diseases, possibly with
little adverse effect on genetic progress in other production traits. Programmes
for resistance to internal parasites to be included in practical breeding
programmes are now in progress. This paper deals with the incentives for focusing
on the three major diseases in Merino sheep, the potential sources of genetic
variation, and the means to exploit these sources of variation. The authors also
highlight gains and benefits achieved in experimental selection flocks, and the
difficulties and options available for commercial breeders.
PMID- 9638821
TI - Genomic approaches to the improvement of disease resistance in farm animals.
AB - As a result of the difficulties in improving disease resistance in farm animals
by traditional phenotype selection, the achievement of such improvement is one of
the most important applications of genome research. The major hurdle to this
important goal is the collection of informative disease records to enable the
segregation of disease resistance loci (DRL) to be traced in pedigrees. This
paper reviews the principles for DRL identification by association analyses or by
linkage analyses. Once linkage has been established, the location of the DRL may
be further refined, a process which may eventually lead to the molecular
characterisation of the causative gene(s) and mutation(s). A reliable map
assignment of a DRL is sufficient for the practical utilisation of this
knowledge, since the inheritance of the DRL can be traced by flanking markers.
Marker-assisted selection concerns the use of linked markers for selection within
populations, while marker-assisted introgression is used if DRL alleles are
introgressed from a donor (resource) population.
PMID- 9638822
TI - Genetic databases: online catalogues of inherited disorders.
AB - Current information on inherited disorders in domestic animals is available on
the internet: Online Mendelian inheritance in animals (OMIA) and Mendelian
inheritance in sheep (MIS) are the two major sources of information. OMIA was
created (and is maintained) by workers at the University of Sydney. MIS has been
compiled by the Committee on Genetic Nomenclature of Sheep and Goats (COGNOSAG),
an international group of geneticists. In the future, similar catalogues for
other species (starting with goats and cattle) will be made available by
COGNOSAG. Electronic access to this information is freely accessible on the world
wide web at http:/(/)www.angis.su.oz.au/Databases/BIRX/om ia (for OMIA),
http:/(/)probe.nalusda.gov:8300/animal/omia.h tml (for OMIA in the United States
of America) and at http:/(/)www.angis.org.au/Databases/BIRX/mis (for MIS).
PMID- 9638823
TI - Lessons from gene knockouts.
AB - The authors describe the technique for the application of homologous
recombination in embryonic stem cells, which is now widely used to engineer mice
which carry specific knockouts of genes. A summary is given of some of the
knowledge of the pathogenesis of and resistance to infections with parasites,
bacteria, or viruses which has accumulated during recent years, based on the
investigation of knockout mice. Special emphasis is placed on knockout animals
which lack components of the cytokine network, lack genes which are critical for
the correct presentation of antigens or are deficient in different immune cell
subsets. In addition, a brief explanation is offered of the possibilities for
inducing targeted deletions or mutations in genes of livestock species (e.g., by
nuclear transfer or by mutagenesis using the alkylating agent N-ethyl-N
nitrosourea) which could lead to the breeding of animals which are resistant to
infectious diseases in the future.
PMID- 9638824
TI - Transgenic approaches to the increase of disease resistance in farm animals.
AB - Molecular genetics and reproductive biology techniques enable the transfer of
foreign DNA into mammals. Novel approaches to modify disease resistance or
susceptibility in livestock are justified by economic and animal welfare
concerns. Current research on the improvement of disease resistance by gene
transfer focuses on three main strategies, as follows: a) somatic gene transfer,
i.e., nucleic acid vaccines b) deletive germ-line gene transfer, i.e., gene
knockout c) additive germ-line gene transfer. These strategies aim at either the
transient or stable expression of components known to influence non-specific or
specific host defence mechanisms, or the disruption of genes known to cause
susceptibility to disease. Referring to the source of the effective agent and the
site and mode of action, the strategies are termed 'genetic', 'congenital',
'intracellular' and 'extracellular' immunisation. Each gene transfer experiment
has to be evaluated carefully with respect to the potential to create novel cases
of pathogen resistance or to lose species barriers or cell-type restrictions.
PMID- 9638825
TI - A miniaturized artificial mastoid using a skull simulator.
AB - A miniaturized artificial mastoid of size and weight that allow calibration and
measurement of bone conduction hearing aids in a conventional audiometric
soundproof box has been developed. Its level of mechanical impedance corresponds
to the standard IEC 373 (1990) within the frequency range 250 Hz to 8 kHz. The
miniaturized artificial mastoid consists of three parts: coupler, skull simulator
(TU-1000), and an external electrical correction filter. The coupler is a highly
damped mass-spring system designed to give the miniaturized artificial mastoid
mechanical impedance in accordance with the standard IEC 373 (1990). It was found
that the miniaturized artificial mastoid yielded results that are in
correspondence with results obtained with the Bruel & Kjaer type 4930 artificial
mastoid for frequencies above 450 Hz. Thus, at these frequencies, the
miniaturized artificial mastoid can be used for audiometer calibration as well as
measurement of bone conduction hearing aids.
PMID- 9638826
TI - Influence of electrode position on near-threshold recording of auditory evoked
brainstem potentials.
AB - Use of brainstem potentials in audiology is based on identifying a response in
the near-threshold range. Wave V has turned out to be the component of the
brainstem potentials that can be detected with a great deal of reliability when
assessment of the threshold for the particular stimulus is desirable. As the
detection of Wave I can be dispensed within audiologic diagnosis, the question
arises as to whether or not a non-cephalic reference electrode compared to the
common lateral position of the reference electrode on the ipsilateral mastoid
produces a more stable Wave V of increased amplitude. In a group of 20 normal
hearing adults, near-threshold stimulation with clicks was conducted and the
brainstem potentials recorded simultaneously with the reference electrode placed
in four different locations (ipsilateral mastoid, contralateral mastoid, non
cephalic electrode, and ipsilateral earlobe). At all of the three intensities
studied (10 dB nHL, 20 dB nHL and 30 dB nHL), recording with the non-cephalic
reference yielded the highest amplitudes, the finding being statistically
significant.
PMID- 9638827
TI - Auditory function in 70- and 75-year-olds of four age cohorts. A cross-sectional
and time-lag study of presbyacusis.
AB - Within the framework of the gerontological and geriatric population studies in
Goteborg, Sweden, 473 elderly persons were examined using pure-tone audiometry in
two recent cohorts. The aim of this study was to present cross-sectionally
acquired hearing data in these contemporary groups aged 70 and 75. Another
objective was to compare hearing function at the same age over the last two
decades (time-lag study) in three 70-year-old cohorts and three 75-year-old
cohorts. The largest time-lags were 14 years (75-year-olds) and 21 years (70-year
olds). The most recently tested cohort of 70-year-olds, studied in 1992,
demonstrated median pure-tone averages (PTA: 0.5, 1 and 2 kHz) of 20.2 dB HL in
the left ear of men and 18.2 dB HL in women. The left median pure-tone thresholds
at 4 kHz were 56.0 dB HL in men and 34.7 dB HL in women. Hearing acuity in 70
year-olds was not demonstrated to have changed in any consistent fashion over a
21-year time-lag. For the most recently evaluated 75-year-olds, the median PTA in
the left ear was 27.3 dB HL in men and 21.6 dB in women. The left median 4 kHz
threshold was 67.3 in the male group and 45.5 dB HL in the female group. Hearing
in 75-year-olds over a time-lag of 14 years demonstrated somewhat better pure
tone thresholds predominantly in the men's better ear in the earliest cohort when
compared to the cohort tested in 1990-91. However, there were no consistent
differences of pure-tone thresholds between these age cohorts, except for the
intermediate cohort 2, in which the men had generally worse hearing. Thus, there
was no apparent evidence of changes of the auditory function in elderly of the
same age over the last two decades. Gender-specific dissimilarities in annual
pure-tone threshold deterioration between the ages of 70 and 75 were found and
are discussed.
PMID- 9638828
TI - Epidemiology of moderate to profound childhood hearing impairments in northern
Finland. Any changes in ten years?
AB - The epidemiology of childhood hearing impairments was studied in a clinical
series of the birth cohorts for 1973-82 and 1983-92 from a geographically well
defined area. The overall prevalence of hearing impairments with PTA0.5-4 kHz >
or = 40 dB was 1.2/1000 live births. Even in the later cohort, the median age
ascertainment was 2.6 years for the congenital or early acquired group and 3.0
years for all impairments. Risk indicators for hearing impairment were present in
half of the children, and those referred for the risk were ascertained at the
median age of 1.1 years. The delay from suspicion to ascertainment was over a
year in about one fifth of cases, while the median time from referral to
ascertainment was only 1.8 months. The planning and implementation of neonatal
hearing screening are suggested, and general information is given on
paedoaudiology for both parents and professionals. A database could be beneficial
in increasing the systemacy of the diagnostic process.
PMID- 9638829
TI - Equivalent threshold sound pressure levels for Sennheiser HDA 200 earphone and
Etymotic Research ER-2 insert earphone in the frequency range 125 Hz to 16 kHz.
AB - Equivalent Threshold Sound Pressure Levels (ETSPLs) have been determined for the
Sennheiser HDA 200 earphone and the Etymotic Research ER-2 insert earphone.
Thirty-one young normal-hearing test subjects participated and the thresholds
were determined for all recommended frequencies in the frequency range 125 Hz to
16 kHz. The results for the HDA 200 earphone are generally in very good agreement
with the results from two other investigations which are available at present.
Only at 6 kHz is a 9 dB deviation found and at 8 kHz a 6 dB deviation is found
between the three investigations. For ER-2 it has not been possible to find other
ETSPL determinations in the literature.
PMID- 9638830
TI - Agreement between two tympanometers. A methodological study of instrument
comparison.
AB - When old instruments are replaced by new ones, agreement between them becomes
important when comparing measurements. Their precision, too, is important. A
common, however inappropriate, statistical approach in these cases is correlation
analysis. As an alternative, a simple statistical method is suggested, in which
differences between measurements of either instrument are plotted against their
means. The distribution of the differences is tested against 0 (one-sample t
test), and for good agreement P > 0.05. This statistical method was used in a
group of 32 adults in which measurements taken with an older automatic
tympanometer and a new digital one were compared. Static compliance and and
gradient showed good agreement, while middle ear pressure showed a significant
bias between instruments explained by phase delay. This disagreement was
insignificant for clinical purposes, but may be important in scientific studies.
The same statistical principle applies determining the precision of each
instrument. The new digital instrument showed higher precision than the older
one.
PMID- 9638831
TI - Normative Wave V latency-intensity functions using the EARTONE 3A insert earphone
and the Radioear B-71 bone vibrator.
AB - Early auditory evoked response (ABR) audiometry is useful for estimating auditory
sensitivity in infants and other difficult-to-test populations. Several
investigations advocate using bone-conducted stimuli, in addition to air
conducted stimuli, for screening infants with hearing loss or for ascertaining
the presence and magnitude of a conductive hearing loss. The present study was
designed to gather normative Wave V latency-intensity data with an insert
earphone (EARTONE 3A) and a bone vibrator (Radioear B-71). Forty normal-hearing
subjects were tested with air-conducted and bone-conducted clicks at intensities
of 55, 40, 30, 20, and 10 dB SL. The stimulus waveforms showed a click onset
delay of 0.1 ms for the 3A insert earphone. It is important to note that our ABR
latencies were not adjusted to account for these differences. The results
revealed that both the air-conduction and bone-conduction functions exhibited
Wave V latencies of 7.0 ms at 55 dB SL. Although both functions exhibited
increased latencies as intensity decreased to 10 dB SL, the air-conducted clicks
yielded somewhat longer latencies than the bone-conducted clicks. To allow direct
comparison of the air-conduction and bone-conduction latency-intensity function,
the bone-conduction function must be corrected by approximately +0.3 ms at 40 dB,
+0.4 ms at 30 dB, +0.5 ms at 20 dB, and +0.8 ms 10 dB nHL. No correction is
needed at 55 dB. The present study suggests that it may not be appropriate to
apply a single correction value (e.g., 0.5 ms) to the entire latency-intensity
function. If clinicians elect to use published latency-intensity data, they must
employ procedure similar to those that were used to collect the normative data.
Otherwise, individual clinics should generate normative latency-intensity data
using well-defined procedures. An alternative to generating latency-intensity
functions is to compare ABR air-conduction and bone-conduction thresholds. This
procedure is advantageous because threshold responses are not as sensitive as
latency measures to slight changes in instrumentation and procedures. The
normative air-conduction and/or bone-conduction values presented in this
investigation are offered as a baseline for either latency-intensity or threshold
comparisons.
PMID- 9638832
TI - Anterior versus posterior, and rim-rent rotator cuff tears: prevalence and MR
sensitivity.
AB - PURPOSE: To determine the relative distribution of the locations of rotator cuff
tears, and the sensitivity of anterior versus posterior tears on MR images.
PATIENTS AND METHODS: We identified 110 consecutive patients who had a shoulder
MR and either a partial-thickness or a small full-thickness rotator cuff tear
diagnosed at arthroscopy. From the arthroscopy videotapes, we classified the
tears as centered in the anterior or posterior half of the cuff, and as either in
the critical zone or adjacent to the bony insertion. The original MR
interpretation was compared with the arthroscopic findings. MR sensitivity and
patient age were compared between patients with tears in the anterior and
posterior halves of the cuff. In addition, in patients with partial tears less
than 2 cm in diameter, an age comparison between those with tears in the critical
zone and those with articular surface tears adjacent to the bony insertion (rim
rent tear) was performed. RESULTS: The tear was centered in the anterior half of
the rotator cuff in 79% of the patients younger than 36 years old, and in 89% of
the patients 36 years old and over. The average age of the patients with tears in
the anterior half (44 years) was not significantly different from the average age
of those with posterior tears (40 years) (P = 0.23). The sensitivity of MR for
anterior tears was 0.69, and for posterior tears it was 0.56 (P = 0.17). The
average age of the 9 patients with rim-rent tears was 31 years, while that of the
28 patients with similarly-sized partial tears not involving the insertion was 40
years old (P = 0.048). Five of the nine rim-rent tears (0.56) were interpreted
correctly on the original MR report; two of the other tears were misinterpreted
as intratendinous fluid but were diagnosable in retrospect. CONCLUSION: Even in
patients less than 36 years old, most partial and small full-thickness rotator
cuff tears are centered in the anterior half of the supraspinatus. Although our
figure for MR sensitivity for these tears is lower than in recent articles, we
found no significant difference between the sensitivity of MR for diagnosing
posterior tears versus tears in the anterior half of the supraspinatus tendon.
Rim-rent tears can be mistaken for intratendinous signal, and should be carefully
looked for in younger patients with shoulder pain.
PMID- 9638833
TI - MRI of fractures of the distal radius: comparison with conventional radiographs.
AB - OBJECTIVE: To compare the evaluation of fractures of the distal radius with MRI
and conventional radiographs. To demonstrate the ability of MRI to detect
unsuspected soft tissue derangement accompanying this common injury. DESIGN AND
PATIENTS: Twenty-one consecutive inpatients admitted following fracture of the
distal radius underwent preoperative evaluation with both conventional
radiographs and MRI. In each case, analysis was made of both the osseous and soft
tissue injury. MRI findings were compared with those identified on conventional
radiographs and at subsequent surgical fixation. RESULTS: Of 21 patients with
fractures of the distal radius, 20 had extension to the radiocarpal articulation,
14 had distal radio-ulnar joint extension and 5 had avulsion of the ulnar
styloid. Occult carpal bone fractures accompanying fracture of the distal radius
were identified in two patients: one of the capitate and the other of the second
metacarpal base. Ten patients (48%) had associated soft tissue injury: six
patients had scapholunate ligament rupture, two patients had disruption of the
triangular fibrocartilage, one patient had extensor carpi ulnaris tenosynovitis
and one patient had a tear of a dorsal radiocarpal ligament. Of five patients
with ulnar styloid avulsions, none had evidence of triangular fibrocartilage
tears. CONCLUSION: MRI affords better evaluation of osseous injury accompanying
distal radial fractures than conventional radiographs. Intra-articular soft
tissue injury accompanies distal radial fractures in almost 50% of cases.
Scapholunate ligament disruption commonly accompanies intraarticular fracture
through the lunate facet of the distal radius. Fracture of the ulnar styloid is
infrequently associated with tear of the triangular fibrocartilage.
PMID- 9638834
TI - MRI of pediatric growth plate injury: correlation with plain film radiographs and
clinical outcome.
AB - PURPOSE: To evaluate pediatric growth plate injuries with conventional
radiographs and magnetic resonance imaging (MRI). To review potential clinical
impact of MRI on subsequent patient management and outcome. METHODS: Fourteen
patients with known or suspected growth plate injury were studied. Each patient
underwent imaging by conventional radiography and MRI within 2 weeks of injury.
Findings on conventional radiographs and on MR images were compared and then
correlated with subsequent management and outcome at a mean of 12 months.
RESULTS: Direct visualization of cartilage afforded by MRI improved evaluation of
growth plate injury in each case. MRI changed Salter Harris classification or
staging in 2 of 9 patients with fractures visualized on conventional radiographs,
allowed the detection of radiographically occult fractures in 5 of 14 cases, and
resulted in a physical change in management in 5 of the 14 patients studied.
CONCLUSION: MRI has an important role in the evaluation of acute pediatric growth
plate injury, particularly when diagnostic uncertainty persists following the
evaluation of conventional radiographs. MRI allows detection of occult fractures,
may alter Salter Harris staging, and in the reported study it frequently resulted
in a change in patient management.
PMID- 9638835
TI - Value of arthrography after supination trauma of the ankle.
AB - OBJECTIVE: To investigate the merits of arthrography after supination trauma of
the ankle. DESIGN AND PATIENTS: In a group of 160 consecutive patients operative
exploration was performed in cases where arthrography and/or a delayed physical
examination showed positive findings. In all patients arthrography was performed
within 48 h after trauma. To determine interobserver agreement, all arthrograms
were independently evaluated by two radiologists, both ignorant of the first
assessment. RESULTS: The prevalence of an ankle ligament lesion was found to be
76%. Of the 122 patients with a rupture of one or more ankle ligaments, 52% had
an isolated anterior talofibular ligament lesion, 3% had an isolated
calcaneofibular ligament lesion, and 45% had combined lesions. The site of the
lesion was predominantly intraligamentous. In the determination of the presence
or absence of an ankle ligament lesion, the specificity and sensitivity of the
ankle arthrogram were 71% and 96% respectively. Interobserver agreement on the
arthrogram was very good (kappa 0.9). In 1% of patients a clear diagnosis was not
possible by means of arthrography. CONCLUSION: Arthrography provides information
of high diagnostic quality with excellent interobserver agreement and therefore
remains the gold standard for early diagnosis (within 48 h) of a lateral ankle
ligament rupture.
PMID- 9638836
TI - Synovial effusion in reflex sympathetic dystrophy: an additional sign for
diagnosis and staging.
AB - PURPOSE: To improve the present MRI criteria for diagnosis and staging of reflex
sympathetic dystrophy (RSD) by including increased joint fluid as an additional
MRI sign of RSD. DESIGN AND PATIENTS: One hundred and fourteen extremities (69
affected and 45 contralateral controls) in 57 consecutive patients with RSD were
evaluated using a 1.5-T unit. T1- and T2-weighted pulse sequences, often with fat
suppression, were used before and after administration of intravenous contrast
enhancement (Gd). Following T2-weighted image digitization the volume of synovial
fluid was measured with a computer model. RESULTS: Effusions were detected in 61%
of the extremities suspected of RSD and in 44% of the contralateral control
joints. The mean fluid quantity measured in the symptomatic articulation was 201
mm3. MRI diagnosis of RSD based on previously described criteria was done in 62%
of the patients, yielding a sensitivity of 60%. Effusions were present in 79% of
the false negative MRI cases. Retrospectively considering the presence of fluid
as a potential positive criterion for RSD increases the sensitivity by 31% (to
91%). CONCLUSIONS: Joint effusions are probably associated with early stages of
RSD. Adding effusion to the list of radiological criteria for RSD increases the
sensitivity of MRI from 60% to 91%.
PMID- 9638837
TI - Subcutaneous granuloma annulare: radiologic appearance.
AB - OBJECTIVE: Granuloma annulare is an uncommon benign inflammatory dermatosis
characterized by the formation of dermal papules with a tendency to form rings.
There are several clinically distinct forms. The subcutaneous form is the most
frequently encountered by radiologists, with the lesion presenting as a
superficial mass. There are only a few scattered reports of the imaging
appearance of this entity in the literature. We report the radiologic appearance
of five cases of subcutaneous granuloma annulare. DESIGN AND PATIENTS: The
radiologic images of five patients (three male, two female) with subcutaneous
granuloma annulare were retrospectively studied. Mean patient age was 6.4 years
(range, 2-13 years). The lesions occurred in the lower leg (two), foot, forearm,
and hand. MR images were available for all lesions, gadolinium-enhanced imaging
in three cases, radiographs in four, and bone scintigraphy in one. RESULTS:
Radiographs showed unmineralized nodular masses localized to the subcutaneous
adipose tissue. The size range, in greatest dimension on imaging studies, was 1-4
cm. MR images show a mass with relatively decreased signal intensity on all pulse
sequences, with variable but generally relatively well defined margins. There was
extensive diffuse enhancement following gadolinium administration. CONCLUSION:
The radiologic appearance of subcutaneous granuloma annulare is characteristic,
typically demonstrating a nodular soft-tissue mass involving the subcutaneous
adipose tissue. MR images show a mass with relatively decreased signal intensity
on all pulse sequences and variable but generally well defined margins. There is
extensive diffuse enhancement following gadolinium administration. Radiographs
show a soft-tissue mass or soft-tissue swelling without evidence of bone
involvement or mineralization. This radiologic appearance in a young individual
is highly suggestive of subcutaneous granuloma annulare.
PMID- 9638838
TI - Skeletal age assessment in children and young adults: comparison between a newly
developed sonographic method and conventional methods.
AB - OBJECTIVE: To compare the performance of a new sonographic (US) method of bone
age estimation with other methods currently in use. DESIGN AND PATIENTS: One
hundred and fifteen subjects underwent left hand/wrist radiography and US
examination of the hip for bone age assessment. For each patient, measurements of
skeletal age were available based on Greulich-Pyle and Tanner and Whitehouse, the
latter being presented in three subtypes (RUS, carpals, and B20) in addition to
the US values. To assess agreement between methods, each method was compared with
every other method. Differences between calculated skeletal age and chronological
age were assessed, and the sensitivity, specificity, and predictive values of
each method computed. RESULTS: Coupled B20/RUS values showed the best agreement,
with 95% of observations within 2.45 years of each other, followed by
carpals/B20, B20/GP, and GP/RUS. The US method agreed the least (difference of
4.19-5.13 years) with the other methods. The US method provided 85.8% (US vs RUS)
to 91.3% (US vs GP) concordant results in recognizing differences between
skeletal and chronological age, and showed a 72.5% sensitivity and a 56.8%
specificity. CONCLUSION: Although the US method promises to permit a safe and
cost-effective assessment of skeletal age, its low accuracy makes it currently
unsuitable for clinical use.
PMID- 9638839
TI - Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud's
syndrome.
AB - Mazabraud's syndrome, though uncommon, is reported increasingly frequently. It
represents an entity readily recognisable radiologically on MR imaging. Awareness
of the syndrome, particularly when the myxoma is solitary, can prevent
misdiagnosis of intramuscular myxomas (especially when large) as malignant
mesenchymal tumors containing myxoid tissue. We review the 34 cases previously
reported in the literature and include a recent case from our center.
PMID- 9638840
TI - Focal myositis.
AB - Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep
soft tissue of the extremities, and is a relatively rare lesion. There is a wide
clinical spectrum, with approximately one-third of patients with focal myositis
subsequently developing polymyositis, and clinical symptoms of generalized
weakness, fever, myalgia, and weight loss, with elevation of creatine
phosphokinase. We report the case of a patient with focal myositis who
subsequently developed myositis ossificans-like features.
PMID- 9638841
TI - Tibial plateau erosions associated with lateral meniscal cysts.
AB - Although meniscal cysts are common, erosions of bone caused by these cysts are
quite rare. We report MR imaging findings of two cases in which lateral meniscal
cysts resulted in erosion of the lateral tibial plateau.
PMID- 9638842
TI - Condensing osteitis of the clavicle in a man.
AB - Condensing osteitis of the clavicle is a rare, benign, usually painful condition
leading to sclerosis of the medial end of the clavicle. In the English language
literature, this has only been reported in women since its original description
by Brower et al. in 1974 [1]. We report a clavicular lesion occurring in a man
that is clinically, radiographically, and histologically identical to described
cases of condensing osteitis.
PMID- 9638843
TI - Schnitzler's syndrome.
AB - We report on a case of Schnitzler's syndrome, focusing on pattern of bone
involvement and its differential diagnosis.
PMID- 9638844
TI - Dual renal grafts: expansion of the donor pool from an overlooked source.
AB - This is a review of the emerging practice of dual renal allografting. In the
setting of the expanded criteria cadaveric (and usually older) donor with
inadequate function to allow single kidney transplantation, both kidneys have
been transplanted into a single recipient. The recipient and donor have often
been matched for age and size as dictated by the concept of nephron dosing. The
reported results of dual grafting are excellent and statistically comparable to
contemporaneous single cadaveric grafts. Criteria are evolving regarding when to
apply single or dual grafting. Wider acceptance of dual renal grafting could have
a significant impact on the cadaver kidney shortage.
PMID- 9638845
TI - Intragraft cytokine gene expression: implications for clinical transplantation.
AB - As our knowledge of the cytokine network in experimental transplant models grows,
we need to understand how and to what extent cytokines mediate the various donor
directed immune events in clinical situations. This overview of clinical cytokine
measurements shows that specific intragraft cytokine messenger RNA (mRNA)
expression profiles can be associated with acute rejection, that they may reflect
the efficacy of immunosuppression, and that they can identify patients at risk
for the development of early chronic rejection. The literature also shows that
acute rejection and immunological quiescence in humans are not restricted to the
cytokine patterns defined in the type 1/type 2 paradigm. This apparent lack of
association may be caused by the immunosuppression used in the clinic but may
also be the result of the infinite diversity of donor and recipient factors, in
which polymorphisms in cytokines and cytokine receptor genes may play a central
role.
PMID- 9638846
TI - A comparative study of FK506 granules and capsules in renal transplant
recipients.
AB - Nine renal transplant recipients in stable systemic condition on FK506 capsules
were converted to FK506 granules in order to investigate the safety, efficacy,
and pharmacokinetics of the granular formulation of FK506. The study period for
the administration of FK506 granules was 4 weeks, and in principle, the oral dose
was the same as that of the FK506 capsules. Renal graft function remained stable
and no rejection signs were noticed while the patients were taking the granules.
The area under the blood concentration-time curve (AUC), the maximum blood level
(Cmax), and the time to reach Cmax (Tmax) after FK506 capsules and FK506 granules
were, respectively, 93.1 +/- 66.4 and 97.0 +/- 89.1 ng.h/ml (P = 0.81), 12.7 +/-
7.1 and 15.2 +/- 11.7 ng/ml (P = 0.39), and 2.0 +/- 1.7 and 1.3 +/- 0.6 h (P =
0.29). The mean trough blood level during FK506 medication was 4.25 +/- 3.42 and
4.02 +/- 3.83 ng/ml, respectively, for the capsules and the granules. FK506
granules, a new formulation, showed an efficacy comparable to that of the FK506
capsular formulation.
PMID- 9638847
TI - Donor pretreatment with ambroxol or dexamethasone fails to ameliorate reperfusion
injury in experimental lung transplantation.
AB - Based on the known properties of ambroxol and dexamethasone to inhibit
inflammation and increase endogenous surfactant levels, the potential advantage
of donor pretreatment with either drug was investigated in an acute rat double
lung transplant model. Donor animals were randomly assigned to one of three
treatment groups: an ambroxol group (AMB; 0.4 mg/kg), a dexamethasone group (DX;
2 mg/kg); or an untreated control group (CN). Drugs were given intraperitoneally
6 h prior to harvest. Following standard preservation and 16 h of cold ischemia,
the donor double lung block was implanted into syngeneic recipients using custom
designed stents for the vascular anastomosis. During reperfusion, serial
measurements of graft pulmonary vascular resistance and alveolar-arterial oxygen
difference were obtained. Separate graft ventilation allowed determination of
graft dynamic lung compliance. Final assessment included weight gain and
histology. For phospholipid analysis, lung lavages were performed in the three
study groups at the end of reperfusion and compared to levels before graft
harvest. Donor pretreatment did not significantly affect preharvest phospholipid
levels. Survival following graft ischemia and reperfusion was shortest after AMB
(92 +/- 5 min) and longest after DX (110 +/- 5 min; DX vs AMB P < 0.03) and CN
(116 +/- 4 min; CN vs AMB P < 0.02). DX pretreatment provided better compliance
(P < 0.02) and lower vascular resistance (P < 0.0001) than AMB treatment. Airway
resistance was lower in the AMB and DX groups than in controls (P < 0.04 and P <
0.02, respectively). The alveolar-arterial oxygen difference was markedly similar
in all groups. Graft weight gain amounted to 114% +/- 10% in AMB, 88% +/- 12% in
DX, and 98% +/- 13% in CN (P = NS). Thus, in this rat lung transplantation model,
donor pretreatment with dexamethasone did not improve graft function compared to
untreated controls and donor pretreatment with ambroxol was found to be
potentially detrimental to graft function during reperfusion.
PMID- 9638848
TI - Allogenic grafting of vascularized bone segments under immunosuppression.
Clinical results in the transplantation of femoral diaphyses.
AB - Trauma surgery lack, substitute, for the reconstruction of large defects of the
long bones. Encouraged by the promising results of bone allotransplantation in
animal models, we successfully performed vascularized bone transplantation in
humans. Vascularized femoral diaphyses were allogenically transplanted into three
patients suffering from chondrosarcoma or post-traumatic osteomyelitis with
postoperative immunosuppression. The bone segments were harvested from multi
organ donors and perfused with UW solution. After back-table preparation, the
grafts were transplanted into the defect zone. Interlocking devices were used in
these operations. Vascular anastomoses were performed in end-to-side technique.
The early clinical course of the patients was not free of anatomical, technical,
or immunological complications. However, all patients are currently free of
malignancy and infection. They are also free of pain and full weight bearing. We
conclude that allogenic grafting of vascularized bone segments has the potential
to become an alternative for the replacement of large bone defects.
PMID- 9638849
TI - Single centre experience with mycophenolate mofetil for refractory rejection in
cadaveric renal transplantation.
AB - Ten patients with refractory rejection following renal transplantation were
treated with mycophenolate mofetil (MMF) in an attempt to salvage the allografts.
All cases of rejection were biopsy-proven. Seven of the patients had initially
been on tacrolimus-based triple therapy and three were on cyclosporin-based
regimens. Those on cyclosporin had been unsuccessfully converted to tacrolimus
prior to receiving MMF. All patients had received at least one course of
methylprednisolone pulse therapy and three had been given OKT3 prior to MMF. MMF
was prescribed at a dose of 2000 mg per day in two divided doses and was given in
addition to tacrolimus and prednisolone. Eight of the ten patients showed
evidence of reversal of rejection, as indicated by improvement in renal function
following commencement on MMF, whilst two patients experienced ongoing rejection
and underwent graft nephrectomy. One of the patients successfully treated has
since had his MMF discontinued due to gastrointestinal intolerance. We conclude
that MMF is effective in salvaging renal allografts with resistant rejection and
that it has an acceptable side-effect profile.
PMID- 9638850
TI - Optimal pH for simple cold storage or machine perfusion of dog kidneys with UW
solution.
AB - Metabolic suppression by temperature is a key to successful organ preservation.
Additional methods for inducing metabolic suppression may further improve organ
preservation. Extracellular acidosis has been shown to suppress warm anoxic
injury to various isolated cells. Acidosis may suppress enzymes with a pH optimum
at the pH of the cytosol (pH 7.3). In this study, the combination of hypothermia
and acidosis was used to determine if it would improve renal preservation. Dog
kidneys were cold-stored (CS) for 48 h in University of Wisconsin (UW) solution
with the pH adjusted to 6.4, 6.8, 7.4, or 7.8. Kidneys were also machine-perfused
(MP) for 3 days with the gluconate perfusion solution (Belzer's machine perfusion
solution, MPS) at pHs similar to those tested for CS. Renal function (serum
creatinine, SCr) and survival were recorded in immediate contralateral
nephrectomized recipients. On the basis of maximum SCr values, kidneys preserved
by CS or MP were best preserved at pHs of 7.4 or 7.8. At a pH of 6.8, SCr values
were elevated and returned to normal at a slower rate than in those preserved at
higher pHs. This study shows that acidosis is not cytoprotective to cold-stored
dog kidneys and causes preservation/reperfusion injury.
PMID- 9638851
TI - Situs inversus of donor or recipient in liver transplantation.
AB - Situs inversus is a rare anatomical abnormality that is often associated with
multiple, complex malformations. In the past, patients with situs inversus were
considered unsuitable candidates for transplantation or organ donation because
associated visceral, and especially vascular, anomalies pose special technical
difficulties. Recently, several cases of successful liver transplantation in
recipients with situs inversus have been published using modified surgical
techniques. This report reviews the literature and describes our own experience,
including two liver graft recipients with complete and incomplete situs inversus,
and one patient who underwent successful transplantation using a liver from a
donor with situs inversus.
PMID- 9638852
TI - A validated technique for the analysis of biliary bile acid secretion in donor
livers prior to transplantation.
AB - Many parameters currently used for the pre-transplant assessment of liver
allografts, are not reliable enough in predicting the likelihood of early graft
dysfunction or non-function. It is generally accepted that bile secretion is a
sign of hepatic function post-transplant and that bile flow shows a close linear
relationship to the secretion of bile acids ("apparent choleretic activity"). We
have studied bile flow, biliary bile acid concentrations and composition and
measured apparent choleretic activity from hepatic bile collected with a new
technique under controlled conditions at the time of retrieval from 18 donor
livers. More than three samples were collected from each of 13 donors and a total
of 65 samples of hepatic bile were analysed. Of these, ten showed typical
apparent choleretic activity with a positive slope in the regression line
analysis (correlation coefficient of 0.9), validating our collection technique.
PMID- 9638853
TI - High-Na+ low-K+ UW cold storage solution reduces reperfusion injuries of the rat
liver graft.
AB - The isolated perfused rat liver model was used to assess graft viability after 24
h of cold preservation. Two solutions were compared for liver preservation:
Belzer's original UW solution (high-K+ UW) and a solution containing the same
components but with inverted concentrations of sodium and potassium (high-Na+
UW). During the 120 min of normothermic reperfusion, livers preserved in the high
Na+ UW solution released lower levels of creatine kinase-BB isoenzyme,
transaminases (ALT and AST), and potassium than those preserved in the high-K+ UW
solution. Bile flow and biliary excretion of indocyanine green increased when
livers were preserved in the high-Na+ UW solution. We found no statistical
differences for oxygen consumption and tissue ATP concentration. The results of
this study support the concept that a high-Na+ UW solution is a more effective
means of preserving rat livers, at least after 24 h of cold-storage and 120 min
of reperfusion in the isolated perfused model, than the original high-K+ UW
solution. Liver preservation in the high-Na+ UW solution reduces damage to
sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like
Belzer cold storage solution eliminates potassium-related problems in cold
preservation and subsequent normothermic reperfusion while keeping all the
qualities of the original UW solution.
PMID- 9638854
TI - A randomized prospective study comparing low-dose OKT3 to low-dose ATG for the
treatment of acute steroid-resistant rejection episodes in kidney transplant
recipients.
AB - Acute steroid-resistant rejection episodes in kidney allograft recipients require
treatment with antilymphocyte antibodies. Monoclonal anti-CD3 and polyclonal
antilymphocyte antibodies have been widely used but seldom compared. Recent data
have suggested that these antibodies could be used at reduced doses without
jeopardizing their efficacy. In this study, we randomized renal transplant
recipients who encountered a first acute steroid-resistant rejection episode to
low-dose ATG or low-dose OKT3 treatment. Sixty patients were enrolled in the
study. They received prophylactic immunosuppression with cyclosporin,
azathioprine, and prednisolone. Treatment of biopsy-proven rejection consisted of
a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was
484 +/- 110 mg, i.e., 0.75 mg/kg per day. The total OKT3 dose was 32 +/- 4 mg,
i.e., 0.05 mg/kg per day. We compared reversion of rejection, side effects,
immunodepression, and graft function. Reversion of rejection was similar in the
two groups, although we noted a trend in favor of ATG. Results were 3% vs 10%
early graft failures, 13% vs 23% overall graft failures, 28% vs 38% 3-month
actuarial incidence of rebound rejection, and 89% vs 81% 1-year graft survival
rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3
group due to the first-dose syndrome. Infections and cancers occurred with the
same frequency. ATG resulted in a deeper and longer decrease in peripheral
lymphocyte subsets. Graft function was similar in the two groups. We conclude
that low-dose ATG and low-dose OKT3 are equally effective in reversing steroid
resistant acute rejection. Tolerance was better with ATG, which also gave a more
potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3
did not appear to lessen their efficacy.
PMID- 9638855
TI - Bradycardia in children less than two years of age during liver transplantation.
PMID- 9638856
TI - Prevention of ischemic injury in the small intestine.
PMID- 9638857
TI - Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California,
July 1995.
AB - The final assignment of antibody clusters for leucocyte antigens and
immunoglobulins, as described in detail in Sections 3 and 4, is summarized in
Table 4. Together with other mAbs developed outside of ELAW II (Table 9) this
pool of reagents represent a powerful array of tools for the study of equine
immunity. The Second Equine Leucocyte Antigen Workshop made considerable advances
in pursuing the objectives of establishing the specificities of mAbs and
achieving consensus on the nomenclature for equine leucocyte and immunoglobulin
molecules. Of equal importance, several productive collaborations were fostered
among the participating laboratories and observers. Overall, enormous advances
have been made in the past decade since mAbs specific for equine leucocyte
antigens and immunoglobulins were first reported. There remains enormous scope
and need for further studies of equine leucocyte antigens and immunoglobulins,
both for the purposes of comparative immunology and for the good of the horse. In
the future novel techniques will be required to develop reagents for specific
target antigens such as the orthologues of the CD25 or CD45 isoforms. In studies
of equine immunoglobulins the functional role of the IgG isotypes must be better
established, reagents for IgE must be developed, and cloning of the
immunoglobulin heavy chain genes will be essential if the complexities of the IgG
sub-isotypes are to be elucidated. The tasks still facing the currently small
group of equine immunologists throughout the world remain formidable, and will
only be tackled successfully in a spirit of collaboration.
PMID- 9638858
TI - Production of monoclonal antibodies to six isotypes of horse immunoglobulin.
AB - Stable clones of 18 mouse hybridomas that produce monoclonal antibodies (MAbs) to
six isotypes of horse immunoglobulin were produced. The number of hybridomas of
different specificities are: four to IgGa, four to IgGb, one to IgGc, four to
IgG(T), two to IgM, and three to IgA. The immunoglobulin isotypes purified from
affinity columns bound with each MAb showed variable mobility in agarose-gel
electrophoresis. Migration proceeded from the anode as: IgG(T), IgA, IgM, IgGc,
IgGb and IgGa. The purified isotypes also demonstrated a single precipitin line
when in immunoelectrophoresis against isotype-specific or polyclonal antisera,
raised against the purified isotype or whole equine serum, respectively.
PMID- 9638859
TI - Monoclonal antibodies to subclass-specific antigenic determinants on equine
immunoglobulin gamma chains and their characterization.
AB - This paper describes the production of a panel of monoclonal antibodies (mAbs)
identifying the four recognised equine IgG subisotypes IgG, IgGa, IgGb, IgGc and
IgG(T). Pure preparations of the subisotypes for use in immunisations and testing
were produced using a combination of gel filtration, salt precipitation, ion
exchange chromatography and protein A and Protein G affinity chromatography. The
specificity of mAbs for the IgG subisotypes was confirmed using ELISA assays, by
characterisation of affinity purified proteins recognised by the mAbs, and by
Western blotting of equine serum proteins. The expression of equine IgG
subisotypes by B cells was examined by flow cytometry using the panel of mAbs.
PMID- 9638860
TI - The equine homologue of LFA-1 (CD11a/CD18): cellular distribution and
differential determinants.
AB - The equine homologue of the leucocyte integrin LFA-1 (CD11a/CD18) has been
characterized using a panel of four monoclonal antibodies (mAbs). The antibodies
labelled almost all leukocytes, thymocytes and lymph node cells from normal
horses, and immunoprecipitated two noncovalently associated polypeptides with
molecular weights of 180 kDa and 100 kDa, respectively. The antigen recognized by
one mAb could be precipitated by another in this cluster in a sequential
immunoprecipitation assay. The mAbs, however, did not block the activities on
lymphocyte function of one another. A mAb to the beta subunit of human LFA-1
cross-reacted with equine LFA-1, but an antibody to its alpha subunit did not,
suggesting that the beta subunit of the leukocyte integrin may be more highly
conserved. Functionally, H20A and a human CD18 antibody (MHM23) inhibited phorbol
ester-mediated homotypic lymphocyte aggregation, whereas mAb CZ3.2 induced rather
than inhibited the homotypic cell aggregation. The formation of lymphocyte
aggregates induced by CZ3.2 was not blocked by the inhibitory antibodies H20A or
MHM23. CZ3.1 seemed to have little inducible or inhibitory effects on homotypic
cell aggregation. The mAb CZ3.1 defined a unique LFA-1 determinant present on
granulocytes, but absent on lymphocytes in members of an extended horse family,
in contrast to the other antibodies which labelled both granulocytes and
lymphocytes from these animals. In all other horses tested, no differences in
reactivity of CZ3.1 and the other LFA-1 antibodies were observed when the
antibodies were tested on lymphocytes or granulocytes. Our results indicate that
common epitopes are shared' between human and equine LFA-1, and that the
described panel of monoclonal antibodies identifies distinct determinants present
on the equine LFA-1 molecule. The following monoclonal antibodies used in this
study were given official workshop designations at the Second International
Workshop on Equine Leukocyte Antigens (Lunn et al., 1998) CZ3.1 (Cor) = W45;
CZ3.2 (Cor) = W77.
PMID- 9638861
TI - The genome of Staphylococcus aureus: a review.
AB - The genome of Staphylococcus aureus consists of a single circular chromosome (2.7
2.8 mbp) plus an assortment of extrachromosomal accessory genetic elements:
conjugative and nonconjugative plasmids, mobile elements (IS, Tn, Hi), prophages
and other variable elements. Plasmids (1-60 kbp) are classified into 4 classes
and there are 15 known incompatibility groups. Mobile elements of the genome (0.8
18 kbp) appear in the chromosome or in plasmids of classes II and III. Prophages
(45-60 kbp) are integrated in the bacterial chromosome, and they are UV- or
mitomycin-inducible. Temperate bacteriophages of S. aureus are members of the
Siphoviridae and the serological groups A, B and F occur most frequently. In the
paper presented, the characteristics of chromosome, plasmids, transposons and
other genetic elements of S. aureus genome are given and an alphabetical list of
known genes of this species is included.
PMID- 9638862
TI - Cooperative haemolysis between weakly-beta haemolytic human intestinal
spirochaetes and Clostridium perfringens.
AB - Interactions between human intestinal spirochaetes (HIS) related to intestinal
spirochaetosis and intestinal pathogenic anaerobic bacteria were investigated by
searching for the presence of cooperative haemolysis among 39 strains of weakly
beta-haemolytic human intestinal spirochaetes and Clostridium perfringens alpha
toxin producers on plates carrying six different sheep blood agar media. An area
of intense cooperative haemolysis (about 3-10 mm) was observed between all tested
spirochaetal strains and C. perfringens where the clostridial alpha-toxin
diffused toward the colonies of the spirochaetes overlapping part of their growth
zone. The cooperative haemolysis was a potentiation of the haemolysis due to the
single cultivation of human intestinal spirochaetes and C. perfringens and was
observed after anaerobic incubation for 24-48 hours when both bacteria at a
concentration range of 10(8)-10(3) CFU/ml were streaked at a distance of 3-10 mm
to each other. A cooperative haemolysis was also observed between C. perfringens
and weakly beta-haemolytic spirochaetes related to porcine and avian intestinal
spirochaetosis and the spirochaete causing swine dysentery. The present study
indicated that the damage produced in vitro by the clostridial alpha-toxin was
enhanced only on the red blood cells which were in proximity to the HIS colonies
causing the complete lysis of the erythrocytes. It is hence possible that the
potentiation of the damage to red blood cells observed in vitro mimics an in vivo
damage on the membranes of enterocytes to which HIS are attached when intestinal
spirochaetosis occurs and when cytolysins similar to the alpha-toxin are
available in the intestine of the host.
PMID- 9638863
TI - Electrophoretic characterization of exposed outer membrane proteins in
environmental and human Bacteroides fragilis strains.
AB - Bacteriodes fragilis isolated from aquatic environment, from infectious process
and from human feces were compared as to their outer membrane protein
electrophoretic profiles after staining with Coomassie blue and reacting with
antibodies prepared against whole-cell antigens of a reference strain from a
clinical source. A marked homogeneity was found among the strains with these
methodologies. The profiles of all strains obtained after radio-iodination of the
intact cell showed qualitative similarity when compared with the profiles
obtained by the other methods. Thus, these data allow us to suggest the
designation of the peptides observed in the autoradiograms as surface-exposed
proteins. Differences observed in the autoradiograms in the expression of bands
mainly detected at a molecular weight of 28 in the commensal strain 118,310
defined previously as avirulent, in addition to a distinction in the titres of
agglutination with the sera tested and lower reactivity in the immunoblotting
assays, suggest a relationship of the B. fragilis surface architecture with the
virulence potential as well as with the origin of the strain.
PMID- 9638864
TI - Outer membrane proteins of Klebsiella pneumoniae after exposure to ciprofloxacin.
AB - Suppression of bacterial growth of two Klebsiella pneumoniae strains after a
short time exposure to ciprofloxacin at suprainhibitory concentrations was found
(postantibiotic effect-PAE). PAEs induced by ciprofloxacin at 2 x MIC were 4.1 h
and 5.3 h for the strains tested, the concentration of 4 x MIC manifested a
suppression of the bacterial growth which lasted 5.9 h and 6.3 h. Delay of
regrowth of K. pneumoniae strains exposed to suprainhibitory concentrations of
quinolones was shown also by other authors. New information concerning the outer
membrane protein profile of K. pneumoniae after PAE has been found. SDS-PAGE
analysis revealed that outer membrane protein patterns isolated from K.
pneumoniae strains treated with a suprainhibitory concentration of ciprofloxacin
did not show apparent changes as compared to controls.
PMID- 9638865
TI - Detection of Borrelia burgdorferi in urine specimens from dogs by a nested
polymerase chain reaction.
AB - A nested PCR (nested flagellin PCR) carrying an internal E. coli DNA control was
established and compared with an in-vitro culture method for the detection of
Borrelia burgdorferi in urine specimens of dogs. The predicted specific amplicon
of the flagellin gene fla was generated from all cultured strains of B.
burgdorferi tested (comprising three European genospecies). In contrast, all 13
strains of seven other flagellated bacterial species were negative. The PCR
detection limit yielded 20 cells of B. burgdorferi per ml of double-distilled
water and approx. 250 bacteria per ml of dog urine. Using the bacterial culture
method, urine specimens collected from 216 dogs in Germany were all diagnosed
negative for spirochetes by in-vitro culture and dark-field microscopy. In
contrast, DNA of B. burgdorferi was detected in 32 specimens (14.8%) by PCR. 31
urine specimens (14.4%) showed inhibitory activity in the PCR assay. However, 94
(44%) were inhibitory in the culture assay. The majority of the PCR-positive dogs
exhibited major clinical symptoms which have not been reported in the course of
B. burgdorferi infection previously, e.g. cystitis (14/32 dogs) or prostatitis
(5/32 dogs). Our results indicate that the analysis of urine specimens by the
nested flagellin PCR is a highly valuable procedure for the diagnosis of B.
burgdorferi infections in dogs.
PMID- 9638866
TI - Comparison of genetic characteristics of MRSA strains present in a Warsaw
hospital in 1992 and 1996.
AB - Nine isolates of methicillin-resistant Staphylococcus aureus (MRSA) collected in
a Warsaw hospital in 1996 were typed by phenotypic (resistograms) and genotypic
(PFGE and plasmid restriction analysis-REAP) methods. Twenty-four (MRSA) strains
collected in this hospital during a period of the same duration in 1992 and typed
earlier using resistograms and PFGE were also typed by REAP. Comparison of typing
results obtained for isolates from 1992 and 1996 showed that strains
characterised by PFGE patterns of two distinct types described as specific of the
two clonally related groups of Polish MRSA in a multicentre study in 1992 are
continuously present in the hospital. However, MRSA strains representing PFGE
patterns not observed before were also found within the collection from 1996.
REAP typing has proved to have a discriminatory power similar to that of PFGE
analysis. Nevertheless, due to the lack of plasmids or difficulties in plasmid
DNA isolation in 3 out of 33 studied strains, the typability of REAP turned out
to be lower than that of PFGE.
PMID- 9638867
TI - Effect of isoleucine on toxin production by Clostridium difficile in a defined
medium.
AB - Supplementation of a carbohydrate-free minimal medium with a high level (100 mM)
of histidine, methionine, valine, isoleucine, proline and leucine, in particular
isoleucine, markedly increased toxin production by Clostridium difficile VPI
10463. The effect of isoleucine was further examined. Increasing the
concentration of isoleucine from 20 to 100 mM remarkably increased toxin
production, while bacterial growth decreased gradually. Amino acid analysis of
the culture revealed that, at 100 mM isoleucine, consumption of isoleucine was
remarkably increased. During the incubation period when toxin titers increased
markedly but bacterial growth was declining, isoleucine, leucine and cysteine
were taken up preferentially and alanine and cystathionine, which were not found
at 1 mM isoleucine, were produced in large quantities. These findings suggest
that isoleucine may play an important role in toxin production by C. difficile
and that alanine and cystathionine production may be co-regulated with the toxin
production in the absence of fermentable carbohydrates.
PMID- 9638868
TI - Studies of the presence of the virulence factors, adhesion, invasion,
intracellular multiplication and toxin formation in salmonellas of different
origin.
AB - Salmonellas of different origin were classified into two groups (11 strains of
common serovars which had been isolated from organs of calves having died from
salmonellosis and 18 strains belonging to rare serovars which showed uncommon
metabolic characteristics and had been isolated from spices and spiced foods).
The strains were examined with regard to different virulence parameters. All
salmonellas investigated possessed the genetic information on invasion (invA) and
toxin formation (stn). They adhered equally well to epithelial cells, could
penetrate into these and survive and multiply inside the cells. The formation of
toxic substances could be detected in all strains after co-cultivation with
epithelial cells in the CHO-K1 test. Significant differences between the groups
of strains could be demonstrated only for the invasion of epithelial cell
monolayers. Since adhesion, invasion and the ability of intracellular survival
and multiplication as well as toxin formation constitute virulence parameters of
salmonellas, it must be assumed that also the Salmonella serotypes studied which
have been rarely observed epidemiologically constitute a risk for humans.
PMID- 9638869
TI - Influence of stress conditions on Bacteroides fragilis survival and protein
profiles.
AB - Bacteroides fragilis strains isolated from different sources, i.e. 1 strain (AA1)
from an aquatic environment, 1 strain from normal flora (118310) and the type
strain (ATCC 25285) originally isolated from clinical material, were analysed for
both cell envelope proteins composition and surviving under oxidative stress
starvation. All strains examined showed a similar survival response when cultured
in drinking water with a ten-fold decrease in viable counts per day during the 7
days of analysis. The outer membrane protein (OMP) profiles of all strains were
quite similar during the stress period as determined by sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE). However, the periplasmic proteins
of the strain 118310 showed two protein bands at 48 and 58 kDa, respectively,
that were absent in the strains AA1 and ATCC 25285 during the incubation period
in potable water. Whole cells and periplasmic 35S-labelled proteins from bacteria
cultured in drinking water showed a significant increase in proteins at 16, 18,
24, 26, 35, 48, and 58 kDa and 18, 22, 24, 48, 58, and 70 kDa, respectively, in
all strains when compared to cells grown in BHI-PRAS media as detected by
autoradiography following SDS-PAGE. These data suggest that B. fragilis may have
a synthesis mechanism that allows them to adapt to adverse environments.
PMID- 9638870
TI - Activity of silver ions in different media.
AB - A major problem in medicine is the large number of infections associated with
implanted and indwelling devices. Silver coating of medical devices is believed
to preserve infection resistance. Several in vitro and animal studies as well as
clinical observations on silver-nylon, silver-intramedullary pins, silver-oxide
Foley catheters and silver-coated vascular protheses have been interpreted as
successful for the prophylaxis of foreign-body infections. Nevertheless, these
products have not been established in clinical use. In this study we have been
able to present physico-chemical and pharmacological data as well as simple
microbiological experiments explaining the reduced anti-microbial activity of
silver-ions in some biological fluids.
PMID- 9638871
TI - Susceptibility of the anaerobic gram-negative non-sporulating rod, Bilophila
wadsworthia to beta-lactams, beta-lactamase inhibitors, meropenem, metronidazole,
clindamycin and quinolones.
AB - The susceptibility of eighty-seven strain of Bilophila wadsworthia to five beta
lactams, two beta-lactamase inhibitors, meropenem, metronidazole, clindamycin and
two quinolones was determined. Tests were performed by the modified reference
agar dilution technique using triphenyltetrazolium chloride for endpoint reading.
The test strains showed a reduced susceptibility to the beta-lactams, penicillin
G (MIC90 4 micrograms/ml), ampicillin (MIC90 32 micrograms/ml), piperacillin
(MIC90 64 micrograms/ml), cephalothin (MIC90 2 micrograms/ml and cefotaxim (MIC90
4 micrograms/ml). The activity of ampicillin was increased by addition of the
beta-lactamase inhibitor, sulbactam (MIC90 2 micrograms/ml), as was the activity
of piperacillin by the addition of tazobactam (MIC90 4 micrograms/ml) 90.8% of
the strains were found to produce beta-lactamase by the nitrocefin tube method.
All strains were shown to be highly susceptible to meropenem, metronidazole and
clindamycin (MICs < or = 1 microgram/ml). Sparfloxacin (MIC90 1 microgram/ml) and
ciprofloxacin (MIC90 0.5 microgram/ml) were found to be active against most of
the strains tested.
PMID- 9638872
TI - Intracerebellar tuberculoma in a patient with AIDS. A case report.
AB - The incidence of tuberculosis in HIV-infected patients has increased continuously
over the past ten years. Extrapulmonary manifestations have become more frequent
in AIDS patients than in immunocompetent hosts. Here we report about a patient
with an unusual presentation of extrapulmonary tuberculosis. Our case report
indicates that differential diagnosis of brain lesions in HIV-infected patients
should include tuberculosis. In uncertain cases, it is indispensable to obtain
specimens by craniotomy or stereotactic biopsy.
PMID- 9638873
TI - Virulence factors of Staphylococcus aureus in the pathogenesis of endocarditis. A
comparative study of clinical isolates.
AB - It is now generally accepted that adherence of microorganisms to various
components of cardiac valve surfaces or vegetation lodging on the heart valves is
an important early event in the pathogenesis of infective endocarditis. 120
clinical isolates of S. aureus obtained from patients with endocarditis and wound
infections and from nasopharyngeal carriers were quantitatively analysed in vitro
for their ability to bind to fibronectin and to produce protein A and alpha
toxin. Both cell-bound and extracellular protein A were measured and alpha-toxin
was determined as antigen and as haemolytic activity. The highest fibronectin
binding ability was found in carrier strains while no significant differences
between strains were observed regarding the production of protein A. Strains
isolated from patients with endocarditis produced significantly lower amounts of
alpha-toxin than did strains from the other two groups. An inverse relationship
between the production of protein A and of alpha-toxin was noticed in the
material. Animal passage of five strains in an experimental endocarditis model
showed a good reproducibility of the test systems and one strain was upregulated
in its fibronectin binding ability and in alpha-toxin production. These in vitro
results indicate that the fibronectin binding ability is not the decisive
adherence factor and question the role of alpha-toxin as a virulence factor in
endocarditis.
PMID- 9638874
TI - Cloning and sequencing of BeS-1 gene encoding the immunogenic antigen of
Streptococcus sanguis KTH-1 isolated from the patients with Behcet's disease.
AB - In order to analyze the immunopathologic mechanisms of Behcet's disease, the gene
(bes-1) encoding a streptococcal antigen correlated with the disease was cloned
and sequenced, and protein produced by this clone was identified by Western
immunoblotting using serum antibody from the patient. Cellular DNA of
Streptococcus (S.) sanguis serotype KTH-1 (uncommon serotype 1, strain 113-20)
from the patient was extracted and digested with EcoRI. The digested fragments
were cloned into the cloning vector lambda gt11, and then the resulting DNA
library was immunoscreened using the patient's serum antibody to serotype KTH-1.
The immunopositive clone of the 1.5 kbp fragment was subcloned into pUC 118
plasmid (pU8BeS1-1) and sequenced. The sequence showed that the 3'-terminal half
side region of this insert contained 962bp of open-reading frame (ORF)
discontinued at the EcoRI restriction site, and the stop codon was not found. The
nucleotide sequence of the remaining additional 3'-terminal region of this gene
encoding whole BES-1 was determined by genome walking. The whole ORF of bes-1
consisted of 849 amino acid residues with a calculated molecular mass of 95 kDa.
The residues in a portion of the amino acid sequence showed a 60% correspondence
to those of the human intraocular peptide Brn-3b.
PMID- 9638875
TI - Binding of immobilized fibronectin by biliary drain isolates.
AB - Occlusion of biliary stents, as the result of bacterial adhesion and colonization
onto biliary stents, still remains a major problem. Biliary proteins, such as
fibronectin (Fn) and vitronectin (Vn), have been presumed to be involved in the
process of bacterial adhesion to biliary biomaterial. In the present study, Fn
binding by 5 strains of E. coli isolated from biliary drains or from bile was
studied. All strains did not bind detectable amounts of soluble Fn but bound to
immobilized plasma Fn. Adhesion of four strains of E. coli to ovalbumin was
reduced by periodate treatment of ovalbumin, but adhesion to Fn was unaffected.
Adhesion was inhibited by mannose-containing saccharides, trypsin treatment of
the protein, and protease treatment of the bacterial cells. Autoradiography
showed that components of cell extracts from three E. coli strains bind 125I-Fn
but not a 150 kD Fn fragment. The findings indicate that the adhesion of these
bacteria to Fn is a protein-protein interaction, inhibited by D-mannose, and
possibly mediated by fimbrial components.
PMID- 9638876
TI - Expression of outer surface proteins A and C of Borrelia afzelii in Ixodes
ricinus ticks and in the skin of mice.
AB - Several studies have described changes in the expression of proteins, especially
of OspA and OspC, of B. burgdorferi sensu stricto during tick feeding. In this
study, the expression of OspA and OspC of B. afzelii in unfed and feeding I.
ricinus nymphs and in the subsequent adults was followed by means of the
immunofluorescence test. Spirochaetes expressing OspA and OspC were observed in
70% and 80%, respectively of the unfed nymphs. In feeding and in fully engorged
ticks, spirochaetes expressed OspC, while OspA disappeared 24 hours after the
beginning of the blood meal. Spirochaetes expressing OspC in salivary glands were
observed in one engorged tick. After molting, in unfed adults spirochaetes again
expressed OspA and OspC but did so less frequently (6% and 13%, respectively).
The mouse strain (AKR/N or BALB/C) on which ticks had their infectious blood meal
influenced OspC expression in the following tick stage. In the skin of AKR/N
mice, at the tick feeding site, B. afzelii expressed OspC only, as was shown by
immunostaining.
PMID- 9638877
TI - Systemic infection with Yersinia enterocolitica in a hemodialysis patient.
PMID- 9638878
TI - Cytomegalovirus infection in kidney transplant patients: clinical manifestations
and diagnosis.
AB - Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality
after solid organ transplantation. CMV infection after kidney transplantation was
confirmed in 19 (54.3%) out of 35 patients. 16 of these (84.2%) developed CMV
disease. CMV infection was diagnosed based on a fourfold or greater increase of
anti-CMV IgG antibody titre, detection of CMV-IgM antibodies and/or virus
isolation. Primary infection was observed in 3 patients, reactivation in 9 and an
undefined type of infection in 7. In most patients (63%), infection was diagnosed
in the first 2 months, and in 3 patients, after 3, 5 and 9 years following kidney
transplantation. The most frequent symptoms of CMV disease were fever (58%),
pneumonitis (26.3%) and enterocolitis (15.8%). In 53% of the patients, CMV
infection co-occurred with other pathogens such as Candida albicans. Cryptococcus
neoformans, bacteria or viruses (HBV, HCV, HSV). Treatment with polyvalent
globulin (Sandoglobin) or hyperimmune globulin (Cytotect), in combination with
ganciclovir in 7 patients, resulted in a regression of CMV disease.
PMID- 9638879
TI - Characterization of pathogenetic determinants of Candida albicans strains.
AB - The study was an attempt to correlate phenotypic pathogenetic determinants of
clinical Candida albicans strains with their genotype as determined by PCR
fingerprinting. A total of 25 C. albicans strains was tested. Adherence capacity,
hydrophobicity and proteinase production were compared with the genotypes of the
particular Candida strains. The fungal strains represented eleven genotypes. No
correspondence relationship was found between genotype and the markers of
pathogenicity.
PMID- 9638880
TI - Phage restriction and the presence of small plasmids in Salmonella enteritidis.
AB - Between 1990-1994, a total of 16,505 S. enteritidis strains of human, animal and
food origin were phage-typed, using the Hungarian scheme and the changes of
incidence of the dominant phage types were monitored. The incidence of PT1
(corresponding to Ward's PT1 was very high between 1990 and 1992 (67.9-71.0% of
the total S. enteritidis isolates), later, it decreased. The prevalence of PT6
(corresponding to Ward's PT4) was rare until 1992, then it gradually increased.
The phage type and plasmid content of 78 Salmonella enteritidis strains were
determined. Small plasmids were present in 59% of the isolates, together with a
serotype-specific (38 MDa) plasmid. A correlation was found between the presence
of the small plasmid and phage restriction to two phages used for subdividing the
Hungarian phage types 1 (PT1) and 6 (PT6) of S. enteritidis (corresponding to PT1
and PT4 in Ward's typing scheme, respectively).
PMID- 9638881
TI - An avian reservoir (Turdus merula) of the Lyme borreliosis spirochetes.
AB - The reservoir competence of passerine birds for the Lyme borreliosis spirochetes
was studied in an enzootic focus in Switzerland. Skin aspirates and skin biopsies
were used to isolate Borrelia spirochetes from Turdus species. B. burgdorferi
sensu lato was isolated and/or PCR-detected in BSK medium containing skin biopsy
or skin aspirate from 5 blackbirds (T. merula) and one song thrush (T.
philomelos). Seven isolates were obtained from 3 different blackbirds. Either B.
garinii or Borrelia from the genomic group VS116 was found in bird skin samples.
Mixed infection occurred in 2 cases. Tick xenodiagnosis was used to determine
whether blackbirds transmitted Borrelia to ticks. Five xenodiagnoses were
performed on 3 different blackbirds. Borrelia DNA was detected in BSK medium
inoculated with xenodiagnostic ticks from all the passerines tested. Isolates
cultured from xenodiagnostic ticks were obtained from 2 blackbirds. Isolates
belonged to group VS116 (n = 10) and to B. garinii (n = 1). Our study has shown
that Turdus sp. are infected by B. garinii and by Borrelia from group VS116 and
that blackbirds are implicated as reservoirs for these 2 genomic groups of
Borrelia, as they transmit living borreliae to ticks. An association seems to
exist between birds and Borrelia VS116, and to a lesser extent, B. garinii,
similar to the association existing between small rodents and B. afzelii. Our
observations emphasize the fact that different enzootic cycles maintain Lyme
borreliosis spirochetes in nature.
PMID- 9638882
TI - Use of silica as a carrier to recover and prepare waterborne enteric viruses for
detection by RT-PCR.
AB - A rapid, efficient and inexpensive method was developed to concentrate poliovirus
type 1 (PV1), rotavirus (RV) and hepatitis A virus (HAV) from artificially spiked
samples of tap and surface water. The method consists of adsorbing the viruses to
silicon dioxide (SiO2) in the presence of 0.5 mM AlCl3 and adjustment of the pH
to 3.5. The silica-adsorbed virus was collected by low speed centrifugation.
Viral RNA was then extracted with guanidium thiocyanate (GT), and environmental
nucleases and inhibitors of reverse transcriptase and Taq polymerase were further
eliminated from concentrates by sequential treatment with GT, ethanol and
acetone. Subsequent RT-PCR allowed the detection of as few as 1 to 10 TCID50 of
PV1, RV, and HAV in seeded 1 liter samples of tap water. The same protocol was
then used with effluents from two local sewage treatment plants. These samples,
found to be free of HAV, were most commonly contaminated with enteroviruses and
rotaviruses. Addition of 1000 TCID50 of HAV, PV1 or RV to a second 1 liter
sample, taken at the same time from the corresponding surface waters allowed
detection of the input virus without discernible inhibition by amplification
inhibitors. The newly established method seems amenable to scaling up and
promising for virus monitoring in different water types. The method is rapid and
results can be obtained within 24 to 36 hours.
PMID- 9638883
TI - [Potassium as an indicator of anthropogenic contamination of swimming pool
water].
AB - Swimming pool water is processed, filtered and disinfected repeatedly in order to
maintain hygienic conditions. Additionally, fresh water is added. However, it
cannot be avoided, that the concentrations of certain components of swimming pool
water will increase in the course of time. DIN 19,643 regulates that fresh water
supply can be measured by nitrate concentration. Nitrate is mainly formed by
oxidation of nitrogen containing organic compounds. Oxidation reactions are
complex and the amount of nitrate formed by this process depends on specific
factors which may vary in swimming pools with different technical equipment.
Therefore nitrate is only of limited reliability to estimate fresh water addition
in public swimming pools. Main sources for nitrogen containing compounds in pool
water are sweat and urine which contain inorganic compounds like potassium.
Potassium is a direct indicator of contamination. Its concentration is not
influenced by chemical reactions because it is an inert compound. The urine
release into the water of indoor pools was estimated by this parameter to be 77.5
ml/person, in outdoor pools about 60 ml. Potassium concentration in swimming
pools will reach an equilibrium concentration, depending on the size of the pool,
the number of bathers and the amount of fresh water added. This equilibrium
concentration is mathematically calculated in a general approach. In none of 36
swimming pools where potassium concentration was measured, this calculated value
was exceeded. The results indicate that the potassium concentration is a new
valuable parameter to assess the quality of swimming pool water under hygienic
aspects.
PMID- 9638884
TI - [Haloforms in hot spring pools].
AB - Chloroforme is formed during disinfection of swimming pool water in certain
amounts depending on several cofactors. Because of its carcinogenic properties
this compound has been frequently a subject of public discussion over the last
couple of years. Little is known about chloroforme concentrations in spas. Spas
are operated at significantly higher temperatures as compared to other pools, and
the organic contamination may be higher. Therefore, chloroforme is possibly
produced in higher amounts than in regular swimming pools. On the other hand the
air that is blown through the bassin may reduce the concentration of this low
volatile substance. In order to investigate the average concentration, 21 water
samples from spas in public indoor pools were analyzed as to their chloroforme
contend. The median of concentration was 3.8 micrograms/l. The maximum measured
chloroforme concentration was 6.4 micrograms/l. The average chloroforme
concentration in the filtered water was slightly higher than before filtration.
The use of spas does not implicate an increase in chloroforme uptake by bathers.
PMID- 9638885
TI - Factors affecting the bacteriological contamination of commercial washing
machines.
AB - Wash water from self-service washing machines in three commercial launderettes of
Bologna (Italy) were examined to verify which factors affect their bacterial
contamination and to determine which procedures in the laundering process have
the most significant effects on the removal of bacteria. Four washing formulas
were compared: a delicates cycle (programmed temperature 25-30 degrees C; actual
temperature: 28-31 degrees C); a whites cycle (programmed temperature: 80-90
degrees C; actual temperature: 50-57.5 degrees C); a delicates cycle with the
addition of an oxygen-based bleach safe for delicate fabrics and a whites cycle
with the addition of an oxygen-based bleach. Bacterial contamination of washing
machines was higher in the launderette most heavely used, and, furthermore, it
was in relation with the washing temperature and the use of bleaches. The low
temperature laundering cycle (20-30 degrees C) did not guarantee elimination of
bacterial content from either the inside of the washing machine or from the
fabric being washed. Washing with water at a higher temperature, of about 55
degrees C, or adding an oxygen-based bleach to the low temperature cycle did
ensure a significant reduction in bacterial recovery from water samples and
fabrics, but did not prevent bacteria such as P. aeruginosa from surviving inside
the washing machine. Only the addition of bleaches to the hot water program
ensured the almost total elimination of bacteria and also guaranteed their
elimination from protected parts of the drum.
PMID- 9638886
TI - [Johann Sigismund Elsholtz--the forgotten pioneer and German-speaking hygiene].
AB - In 1682, the term "hygiene" appeared for the first time in the German language,
in Johann Sigismund Elsholtz's Diaeteticon. In the author's meaning this term is
used to describe the tenet of the maintenance of good health. In his book,
Elsholtz who was physician at the court of Frederick William, the Great Elector
of Brandenburg, makes suggestions for wholesome food and drinking. He demands the
availability of clean water and of a good air and draws attention to the
importance of personal hygiene. Thus, Elsholtz should be referred to as a German
pioneer of hygiene whose recognition has been long overdue.
PMID- 9638887
TI - [A Salmonella epidemic by Salmonella subspecies II 4,12,12,27:b:- at the
University Hospital of Tubingen in April 1996].
AB - In April 1996 four patients at the University Hospital of Tubingen became ill
with diarrhoea at short intervals; one of the patients also suffered from fever.
From stool samples of all four patients Salmonella subspecies II 4,12,27:b:- was
isolated; from the patient who had fever the pathogen was also isolated from one
blood culture. The patients were treated at different wards of the hospital. All
four patients suffered from underlying diseases. In the course of a
microbiological examination of the central kitchen staff of the hospital
Salmonella subspecies II 4,12,27:b:- was isolated from a stool sample of one of
the employees. No contact to cold blooded animals, no travel abroad and no
symptoms of gastroenteritis were reported by the employee. When the employee had
been temporarily suspended no further Salmonella infections occurred.
PMID- 9638888
TI - Characterization and quantitation of parasite species in the effluents of the
Berisso main sewage channel, Buenos Aires, Argentina.
AB - Outbreaks of disease can be caused by pathogenic intestinal parasites in drinking
water. La Plata, the capital of the province of Buenos Aires, Argentina, is
located on the La Plata River; a principal tributary receiving the raw sewage
from the city's 500,000 inhabitants via the Berisso main septic channel at an
estimated volume of 108,390 m3/day (4516.3m3/h). To determine the parasite
contamination level of the La Plata River, we obtained 18 sewage effluents from
the Berisso main septic channel at its point of discharge into the river and
concentrated these samples by filtration. This approach detected the following
parasites at the indicated average levels (cysts/m3): members of the flagellate
genus Giardia, more than 9000; representatives of the amoebic species Entamoeba
histolytica, slightly more than 800 and Entamoeba coli, 5000; other amoebic
forms, up to 23,000. These data clearly illustrate the degree of contamination
within the La Plata River caused by the Berisso septic channel. Pollution of the
La Plata River to this extent thus presents a high health risk for people who
drink the water from this river even after conventional processing as well as for
those who use the water from this portion of the river for recreation.
PMID- 9638890
TI - Fibromyalgia is not a muscle disorder.
AB - Originally described as "fibrositis," fibromyalgia has long been considered a
muscle disorder, and many studies have investigated the possible pathologic basis
of the disorder by examining muscle tissue, using various methodologic
approaches. Although initial studies suggested a possible pathologic basis in
muscle, most had serious methodologic limitations. More recent studies, however,
have avoided methodologic pitfalls and indicate that the muscles of patients with
fibromyalgia are normal. When data from studies of tenderness are also taken into
account, the weight of evidence suggests that fibromyalgia is a chronic pain
syndrome which has a central rather than peripheral or muscular basis.
PMID- 9638891
TI - Skeletal muscle abnormalities in patients with fibromyalgia.
AB - Widespread muscle pain and tender points are the most common complaints of
fibromyalgia patients, and the underlying mechanisms responsible for these
symptoms have been studied intensively during the past decade. It has been
suggested that fatigue and pain may lead to decreased levels of physical activity
in many patients. The resulting deconditioned state may itself contribute to
muscle abnormalities. Associated symptoms such as disturbed sleep, anxiety,
depression, or irritable bowel also may have a negative impact on muscle function
and level of daily activities. The important interactions between the central
nervous and musculoskeletal systems may involve another element, the
neuroendocrine stress-response system. This review will consider both the current
state of knowledge and also future studies which might be designed to answer more
effectively the outstanding questions regarding the underlying pathogenesis of
fibromyalgia.
PMID- 9638892
TI - Neuroendocrine abnormalities in fibromyalgia and related disorders.
AB - Fibromyalgia (FM) and related syndromes are poorly understood disorders that
share symptoms such as pain, fatigue, sleep disturbances, and psychological
distress. These syndromes are more common in women, and they are associated with
psychological or physical stressors. The neuroendocrine axes are essential
physiologic systems that allow for communication between the brain and the body.
Interconnections among the neuroendocrine axes lead to coordinate regulation of
these systems in both a positive and negative fashion. Several neuroendocrine
axes have been shown to be dysfunctional in patients with FM. Although we do not
yet understand the relationship between the reported disturbances of
neuroendocrine function and the development or maintenance of FM and related
syndromes, the authors have proposed that these abnormalities are important in
symptomatic manifestations. This article reviews data showing disturbances of the
neuroendocrine axes in FM and proposes a hypothesis of the development and
maintenance of FM related to neuroendocrine disturbances.
PMID- 9638893
TI - Sleep in fibromyalgia patients: subjective and objective findings.
AB - Fibromyalgia (FM) patients report early morning awakenings, awakening feeling
tired or unrefreshed, insomnia, as well as mood and cognitive disturbances; they
may also experience primary sleep disorders including sleep apnea. Longitudinal
studies have demonstrated the chronic nature of these disturbances in patients
with FM. A distinct relationship exists between poor sleep quality and pain
intensity. Polysomnographic findings during sleep in these patients include an
alpha frequency rhythm, termed alpha-delta sleep anomaly, which is also seen in
normal controls during stage 4 sleep deprivation; deep pain induced during sleep
in normal controls also causes this anomaly. Sleep architecture is altered in FM
patients showing an increase in stage 1, a reduction in delta sleep, and an
increased number of arousals. Before prescribing pharmacologic compounds aimed at
modifying sleep, adequate pain control and sleep habits should be achieved;
tricyclic antidepressants, trazadone, zopiclone, and selective serotonin reuptake
inhibitors, however, may be required. More research is needed to elucidate the
cellular and molecular mechanisms involved in the sleep disturbances occurring in
patients with FM.
PMID- 9638894
TI - Advances in fibromyalgia: possible role for central neurochemicals.
AB - The neurophysiologic term allodynia has been applied to fibromyalgia because
people with that disorder experience pain from pressure stimuli which are not
normally painful. The nociceptive neurotransmitters of animal studies are now
relevant to this human model of chronic, widespread pain. Evidence is presented
to implicate several chemical pain mediators (including serotonin, substance P,
nerve growth factor, and dynorphin A) in the pathogenesis of fibromyalgia. This
perception is hopeful because it offers many new options for the development of
innovative therapy.
PMID- 9638895
TI - Abnormal functional activity of the central nervous system in fibromyalgia
syndrome.
AB - The evaluation of pain is one of the major problems facing general practitioners
and specialists in medicine. Although the source of pain can be usually be traced
to specific abnormalities in a given organ system, some patients present with
generalized pain syndromes, such as fibromyalgia, for which no specific source
can be found. Some researchers have begun to consider that although there may be
a somatic source of such pain at its initiation, over time the pain may be
maintained or exacerbated by functional alterations in critical regions of the
brain and spinal cord that are involved in pain processing or pain inhibition.
This article describes the techniques currently used to measure regional cerebral
blood flow (rCBF) in the brain by single photon emission computed tomography
(SPECT) imaging, and reviews the SPECT and positron emission tomography
literature concerning alterations in functional brain activity associated with
pain in healthy individuals and in patients with chronic pain, including those
with fibromyalgia. The article concludes by describing the implications of
current knowledge about pain and abnormal functional brain activity in the
understanding of the pathophysiology of fibromyalgia and in the development of
therapeutic strategies to manage patients with this disorder.
PMID- 9638896
TI - Advances in the treatment of fibromyalgia: current status and future directions.
AB - Despite significant efforts devoted to understanding the etiopathogenesis of
fibromyalgia, its treatment still presents a challenge to practicing clinicians,
who must recognize the disorder and quantify the different symptoms in order to
treat it. This article discusses recent research to identify sensitive and
reliable measures for determining response to treatment among patients with FM,
and the elements of therapeutic programs (pharmacologic and nonpharmacologic) for
patients with FM along with the empirical or theoretical basis for their use.
Future directions, including the need for systematic, controlled outcome studies
of therapies and evaluation of variables which may mediate the effects of
treatment, as well as demonstration that the effects produced in outcome studies
generalize to settings beyond those in which the studies are initially conducted,
are also discussed.
PMID- 9638897
TI - Current concepts in the pathophysiology of abnormal pain perception in
fibromyalgia.
AB - Fibromyalgia is a noninflammatory rheumatic disorder characterized by chronic
widespread musculoskeletal pain. Although many studies have described the pain
and other clinical symptoms associated with this disorder, the primary mechanisms
underlying the etiology of fibromyalgia remain elusive. This article reviews
recent data supporting the links among each of three systems--the musculoskeletal
system, the neuroendocrine system, and the central nervous system (CNS), all of
which appear to play major roles in fibromyalgia pathophysiology--and pain in
fibromyalgia, and concludes by presenting a model of the pathophysiology of
abnormal pain perception in fibromyalgia which integrates the research findings
described.
PMID- 9638898
TI - Effect of fiber length on glass microfiber cytotoxicity.
AB - Fiber length has been implicated as a determinant of fiber toxicity. Fibers of
narrowly defined length can be generated by dielectrophoretic classifiers. Since
the quantities of fibers produced are very small, we developed a rat alveolar
macrophage microculture system to study the toxicity of these samples. The
objective of this study was to examine the role of fiber length on the
cytotoxicity of Manville code 100 (JM-100) fibers. Rat alveolar macrophages were
cultured with 0-500 microg/ml of 5 lengths of JM-100 fibers on 96-well plates.
After 18 h, well supernatants were removed and lactate dehydrogenase (LDH)
activity was measured to assess cell damage. Chemiluminescence (CL), an
assessment of macrophage function, was measured by adding lucigenin with or
without zymosan, a particulate stimulus, to appropriate wells. For each fiber
length the effects were concentration dependent: CL declined and LDH rose with
increasing fiber concentration. Comparing the effects of different lengths showed
the greatest toxicity from a relatively long fiber sample (mean length = 17
microm). Microscopic examination of the interaction of fibers with macrophages
revealed multiple macrophages attached along the length of the long fibers. This
suggests that frustrated, or incomplete, phagocytosis may be a factor in the
increased toxicity of longer fibers. Overall the results demonstrate that length
is an important determinant of toxicity for JM-100 fibers.
PMID- 9638899
TI - Ventilatory responses in awake guinea pigs exposed to acid aerosols.
AB - This study reports experiments designed to evaluate the dose and temporal effects
of an atmospheric pollutant, sulfuric acid (H2SO4) aerosol, on the dynamic
components of the respiratory cycle. Ventilation was measured in a whole-body
barometric plethysmograph in unanesthetized, unrestrained animals following a 4-h
exposure to H2SO4 aerosol at 14.1, 20.1, or 43.3 mg/m3. Lung injury was assessed
by histopathology and bronchoalveolar lavage (BAL). Aerosol exposure with H2SO4
caused marked alterations in both the magnitude and composition of the
ventilatory response, which were both dose and time dependent. At the highest
concentration tested, there was a significant increase in tidal volume (deltaVt)
and a decrease in breathing frequency (f) immediately after exposure. Analysis of
BAL fluid at this time showed increased inflammatory cells and protein in the
acid exposed animals, and histology showed hyaline membranes and acute
inflammatory cells in the proximal acinar region. By 24 h postexposure, f
significantly increased whereas deltaVt decreased. This pattern of breathing was
interspersed with short periods of apnea. The onset of rapid, shallow breathing
was associated with histological evidence of diffuse pulmonary edema. By
contrast, the immediate postexposure period at the lowest concentration of H2SO4
aerosol was characterized by a significant increase in f and little or no effect
on deltaVt. These effects diminished with time, and at 24 h postexposure
ventilatory parameters were indistinguishable from baseline values. An apparent
crossover between the effects associated with the high and low exposure
concentrations was seen at the intermediate exposure concentration; however,
closer inspection of these findings on an animal-by-animal basis revealed two
populations of animals with respiratory characteristics of either the high
exposure or low-exposure groups. The data suggest that the guinea pig exhibits
complex interactions between dose and time to response that are consistent with
the activation of neural reflexes. The indirect plethysmographic method provides
a simple means to assess these responses in a model system that avoids the use of
anesthetics, surgery, and restraint.
PMID- 9638900
TI - Regional brain dosimetry of trichloroethane in mice and rats following inhalation
exposures.
AB - While certain neuroactive volatile organic compounds (VOCs) have been reported to
have an uneven distribution in various anatomically distinctive brain regions,
this has not yet been reported for the short-chain aliphatic halogenated
hydrocarbons. Therefore, the uptake and regional brain distribution of 1, 1, 1
trichloroethane (TRI) in mice and rats following inhalation exposure were
examined. Male Sprague-Dawley rats and CD-1 mice were exposed to TRI at either
3500 or 5000 ppm for 10, 30, 60, or 120 min. Seven brain regions from rats and
three from mice were sampled, and TRI concentrations in the blood and brain
tissues were determined by headspace gas chromatography. In both species, the
medulla oblongata was found to have the highest TRI concentrations, while cortex
(in both species) and hippocampus (only sampled in rats) contained the lowest TRI
concentrations. Substantial differences were also observed between the two
species, as the mice exhibited higher capacity to accumulate TRI in the blood as
well as in the brain regions. It appears that lipid content is a main factor
influencing the differential disposition of TRI among the brains regions.
Physiological differences in the respiratory systems of the two species and the
physiochemical properties of the chemical favoring diffusion toward lipid-rich
compartments could also have been expected to account for the patterns of
regional distribution and species differences.
PMID- 9638901
TI - Human in vivo and in vitro hydroquinone topical bioavailability, metabolism, and
disposition.
AB - Hydroquinone is a ubiquitous chemical readily available as monographed in
cosmetic and nonprescription forms for skin lightening, and is an important
industrial chemical. The in vivo bioavailability for 24-h application in humans
was 45.3+/-11.2% of dose from a 2% cream formulation containing
[14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h.
Timed skin wash and skin tape-stripping sequences showed a rapid and continuous
movement of hydroquinone into the stratum corneum of human volunteers. Plasma
levels taken both ipsilateral and contralateral to the topical dosing site
contained radioactivity at the first 0.5-h sampling time. Peak plasma
radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous
absorption with fresh viable human skin gave a bioavailability of 43.3% of dose,
and flux was calculated at 2.85 microg/cm2/h. In vitro, some of the skin samples
were pretreated with the metabolic inhibitor sodium azide, which had no effect on
percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were
extracted and the extracts subjected to thin-layer chromatography (TLC). Control
[14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone.
Receptor fluid and skin extraction had a second peak with the same Rf as
benzoquinone, which was decreased with azide treatment. No other peaks were
found. Ethyl acetate extraction of urine from the in vivo study showed all
radioactivity to be only water-soluble, free hydroquinone released following
glucuronidase treatment. Risk assessment should not only involve the
bioavailability of intact topical hydroquinone, but also consider phase I and
phase II metabolism in both humans and any animal for which toxicity potential
was assessed.
PMID- 9638902
TI - Chlorpropham [isopropyl N-(3-chlorophenyl) carbamate] disrupts microtubule
organization, cell division, and early development of sea urchin embryos.
AB - The herbicide CIPC [N-(3-chlorophenyl) carbamate] has been shown to disrupt
microtubule organization in plants, apparently by interfering with the
functioning of the microtubule organizing center. Very few studies have examined
the effects of CIPC on animal cell microtubules and centrosomes, however, and the
effects of this cytoskeletal disrupting agent on fertilization and early
development have not been studied in detail. To address these questions,
fertilized sea urchin eggs were cultured in the presence of CIPC until the prism
stage, and perturbations in the cytoskeleton and development were examined. It
was found that Lytechinus pictus embryos are sensitive to micromolar amounts of
CIPC, and that a characteristic set of cytoskeletal and developmental deficits is
produced as a result of exposure to this herbicide. Mitotic spindles were
truncated and randomly oriented within zygotes and blastomeres, and cytokinesis
was compromised, resulting in the production of blastomeres of various sizes and
ploidy. Interestingly, in spite of these cytoskeletal and nuclear alterations,
spindle poles at fourth cleavage retained their ability to interact with the
plasma membrane in a manner similar to that normally characterizing the unequal
division of macromeres and micromeres. CIPC treatment resulted in unequal cell
divisions at atypical times, and skeletal spicule formation in these embryos was
abnormal. These results indicate that CIPC may pose a significant health risk
during mammalian embryogenesis; in addition, it may be a useful tool with which
to study microtubule and centrosomal functioning during animal cell division
especially in those cell types that exhibit stereotypic patterns of cell division
during early development.
PMID- 9638903
TI - Evaluation of abnormal liver function in pregnancy.
AB - Liver disease in pregnancy may present in a subtle or dramatic fashion. An
approach using the pattern of liver function abnormalities, time of gestation,
and constellation of symptoms will narrow the diagnostic possibilities.
Diagnostic tests, including serology, ultrasonography of the hepatobiliary tree,
and liver biopsy, can make a definitive diagnosis.
PMID- 9638904
TI - Intrahepatic cholestasis of pregnancy.
AB - Intrahepatic cholestasis of pregnancy (ICP) is a disease of the third trimester
of pregnancy involving pruritus and elevated bile acid levels. Its pathogenesis
likely involves a genetic hypersensitivity to estrogen. Once thought to be benign
for both mother and fetus, ICP has been associated with increased rates of fetal
morbidity and mortality and an increased risk of maternal coagulopathy. Optimal
obstetric management includes delivery after establishment of fetal lung
maturity. Many treatments have been proposed for the maternal medical management
of ICP, none of which is ideal.
PMID- 9638905
TI - Hepatitis in pregnancy.
AB - The study of viral hepatitis was expanded over the past decade with the emergence
of new viruses, therapies, and vaccination guidelines as well as new data on the
risks of perinatal transmission. There are now at least six hepatitis viruses.
Hepatitis A and E are causes of epidemic, enteric infection and do not carry a
significant risk of chronic infection. Hepatitis B, C, D, and G are
hematogenously spread and are significant causes of chronic hepatitis,
hepatocellular carcinoma, and cirrhosis. The following report reviews the types
of hepatitis as well as the consequences of infection to the mother and fetus.
PMID- 9638906
TI - Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a review
of diagnosis and management.
AB - Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a form of
severe preeclampsia that threatens the gravida and her fetus. In this report, the
diagnostic criteria and maternal and fetal risks of HELLP are defined. Prompt
recognition and treatment in tertiary centers is emphasized, because the
prognosis can be adversely affected by delayed or less than optimal diagnosis and
treatment. Management guidelines are offered for treating this disorder. The
potential roles of corticosteroids, plasmapheresis, and expectant management are
critically evaluated. Subsequent pregnancy outcome, contraception, and
preventative strategies are considered.
PMID- 9638907
TI - Acute fatty liver of pregnancy.
AB - Acute fatty liver of pregnancy is a rare clinical entity unique to pregnancy that
occurs during the third trimester. The obstetric team must be familiar with this
disease because early diagnosis and prompt delivery have dramatically improved
prognosis, which was often fatal for both mother and child. Clinicians must have
a high index of suspicion for this condition when a woman has nausea or vomiting,
abdominal pain (particularly epigastric), jaundice, polyuria-polydipsia (without
diabetes), increased serum transaminase activity or thrombocytopenia in late
pregnancy. The disease rarely recurs during a subsequent pregnancy. The cause is
unknown, but some cases of acute fatty liver of pregnancy have been associated
with a genetic deficiency of fatty acid beta-oxidation. Because of the
possibility of this congenital deficiency, infants of affected mothers should
undergo close follow-up from birth.
PMID- 9638908
TI - Liver hematoma and rupture in pregnancy.
AB - Liver hematoma and rupture is a rare but devastating complication of pregnancy.
The majority of cases have been associated with severe preeclampsia, but unlike
typical preeclampsia, it is a disease of older, multiparous patients. Although
there are predictable findings on liver pathology, the underlying pathophysiology
is poorly understood. Early recognition and prompt surgical intervention are
crucial to reduce the high fetal and maternal mortality rate associated with this
disease.
PMID- 9638909
TI - Pregnancy after liver transplantation.
AB - This article reviews the reported experience with pregnancy after liver
transplantation and describes obstetric risks and medical issues that the
maternal fetal medicine specialist has a reference for managing these pregnancies
and for providing appropriate preconception counseling. Women who undergo liver
transplantations have a higher risk of preeclampsia, worsening hypertension,
preterm premature rupture of membranes, anemia, small for gestational age,
preterm delivery, and cesarean section than the normal obstetric population.
Women with preconceptional renal dysfunction appear to be at greatest risk for
pregnancy complications. Women who conceived within 6 months of transplant had a
high risk of rejection. Reproductive-aged recipients of liver allograft should
receive contraception and preconception counseling. In an appropriately timed and
planned pregnancy, women who undergo liver transplantations can have successful
pregnancies with little risk to their allograft function.
PMID- 9638910
TI - Cirrhosis and portal hypertension in pregnancy.
AB - Cirrhosis and portal hypertension infrequently coincide with pregnancy but
increase maternal and fetal morbidity and mortality when present. Chronic liver
disease and portal hypertension are not contraindications to pregnancy but
necessitate intensive monitoring throughout pregnancy. The complications of liver
disease are numerous and pose additional risks. Management of complications
arising during pregnancy is similar to management in the nonpregnant patient.
Provision of optimal care for mother and fetus can require the skills of multiple
specialties such as maternal fetal medicine, gastroenterology, nutrition, and
surgery. This report provides guidelines for the management of cirrhosis and
portal hypertension in pregnancy.
PMID- 9638911
TI - Liver masses in pregnancy.
AB - Liver masses in pregnancy are rare but when encountered pose a difficult clinical
scenario with many diagnostic and management uncertainties. They can be
classified as nonneoplastic and neoplastic and further subdivided into benign and
malignant. Fortunately, benign hepatic adenomas, focal nodular hyperplasia, and
hemangiomas appear to be the more common sources of liver masses identified in
this generally young and healthy patient population, but the actual incidence of
each type is unknown during pregnancy. In some areas of the world infectious
causes are more prevalent. Malignant causes of hepatic masses carry a grave
prognosis, similar to that for the nonpregnant population. The clinical
presentation of a liver mass during pregnancy is similar in presentation to a
nonpregnant patient, although symptoms may initially be attributed to pregnancy,
and diagnosis is therefore delayed. Management varies depending on the etiology
and size of the mass and on gestational age.
PMID- 9638912
TI - Contraception in the patient with liver disease.
AB - Selection of a method of contraception in patients with liver disease can be
complicated. Tubal ligation should be considered in the setting of chronic liver
disease for those patients who have completed families. Multiple reversible
methods of contraception are currently available but may affect hepatic disease.
Estrogen-containing contraceptive methods are contraindicated in patients with
acute liver disease. Progestin contraceptives appear to be safe and multiple
delivery systems are available. With rare exception, barrier methods and the
intrauterine device may be offered as alternative methods.
PMID- 9638913
TI - Effects of a circumferentially vented mask on breathing patterns of women as
measured by respiratory kinematic techniques.
AB - Since pneumotachograph masks are commonly used in studies of speech breathing,
the purpose of this study was to measure the differences in respiratory
volumetric and frequency measures during speech under two conditions: with and
without a circumferentially vented pneumotachograph mask coupled to the face.
Thus we sought to identify whether changes in breathing patterns occur with the
use of a specific face mask, because these patterns are accepted as
representative of normal speech breathing. Subjects were 10 normal-speaking
women, each of whom produced a syllable train and a connected speech task, both
at comfortable intensity levels. Respiratory measures were made using linearized
magnetometers during speech production. The measurements included lung volume,
rib cage volume, and abdominal volume at utterance initiation and termination,
volume excursions during the utterance, and the number of breath groups during
the speech task. There were no significant differences between the mask-on and
mask-off conditions in volumetric and frequency measures. A significant task
difference for abdominal initiation was found. It was concluded that the use of a
circumferentially vented pneumotachograph mask does not alter the reliability of
respiratory volume and frequency measures for studies of voice.
PMID- 9638914
TI - Effect of extended exposure to frequency-altered feedback on stuttering during
reading and monologue.
AB - An ABA time series design was used to examine the effect of extended, continuous
exposure to frequency-altered auditory feedback (FAF) during an oral reading and
monologue task on stuttering frequency and speech rate. Twelve adults who stutter
participated. A statistically significant decrease in number of stuttering
events, an increase in number of syllables produced, and a decrease in percent
stuttering was observed during the experimental segment relative to baseline
segments for the oral reading task. In the monologue task, there were no
statistically significant differences for the number of stuttering events, number
of syllables produced, or percent stuttering between the experimental and
baseline segments. Varying individual patterns of response to FAF were evident
during the experimental segment of the reading task: a large consistent reduction
in stuttering, an initial reduction followed by fluctuations in amount of
stuttering, and essentially no change in stuttering frequency. Ten of 12
participants showed no reduction in stuttering frequency during the experimental
segment of the monologue task. These findings have ramifications both for the
clinical utilization of FAF and for theoretical explanations of fluency
enhancement.
PMID- 9638915
TI - The effect of lung volume on selected phonatory and articulatory variables.
AB - The purpose of the study was to examine the effects of manipulating lung volume
(LV) on phonatory and articulatory kinematic behavior during sentence production
in healthy adults. Five men and five women repeated the sentence "I sell a
sapapple again" under five LV conditions. These included (1) speaking normally,
(2) speaking after exhaling most of the air from the lungs, (3) speaking at end
expiratory level (EEL), (4) speaking after a maximal inhalation, and (5) speaking
after a maximal inhalation while attempting to maintain as normal a mode of
speech as possible. From a multichannel recording, measures were made of LV,
sound pressure level (SPL), fundamental frequency (F0) and semitone standard
deviation (STSD), and upper and lower lip displacements and peak velocities. When
compared with the reference condition, the sentence was spoken significantly more
quickly at the lowest LV. SPL increased significantly for the high LV condition,
as did the women's F0 and STSD. Upper lip displacements and peak velocities
generally decreased for LVs other than the reference condition. Lower lip
movements showed inconsistent changes as a function of LV. Adjustments to the LV
for speech led to SPL and F0 changes consistent with a coordinated control of the
respiratory system and the larynx. However, less consistent effects were observed
in the articulatory kinematic measures, possibly because of a less direct
biomechanical and neural control linkage between respiratory and articulatory
structures.
PMID- 9638916
TI - Nasal coarticulation in normal speakers: a re-examination of the effects of
gender.
AB - The purpose of this study was to re-examine the influence of gender on nasal
coarticulation in normal speakers. Twenty adult speakers (10 men, 10 women)
produced the vowel-nasal-vowel (VNV) sequence /ini/ within a carrier phrase using
two stress patterns: (1) with equal stress placed on both syllables, and (2) with
contrastive stress placed on the second syllable. A partitioned,
circumferentially vented pneumotachograph mask and microphone were used to
determine nasal airflow, ratios of nasal to oral-plus-nasal airflow, and sound
pressure levels (SPLs) at the midpoints of the first and second vowels of the
syllables. Volume ratios of nasal to oral-plus-nasal airflow that reflected the
entire duration of the vowels were also obtained. Results indicated that all
speakers except 1 woman exhibited nasal airflow at the midpoint of the first
vowel when /ini/ was produced with equal stress; all speakers exhibited carryover
nasal airflow during the second vowel. During contrastive stress, all speakers
except 1 woman and 1 additional man exhibited anticipatory nasal airflow; all
speakers exhibited carryover nasal airflow. Analysis of variance (ANOVA)
procedures with repeated measures indicated significant main effects of syllable
stress (p < 0.001) relative to nasal airflow and ratios of nasal to oral-plus
nasal airflow. Regardless of the gender of the speakers, syllable stress resulted
in reduced anticipatory and carryover nasal airflow during the first and second
vowels of /ini/, respectively. The results suggest that (a) both men and women
adhere to similar patterns of velar articulation, and (b) velopharyngeal closure
during the vowel /i/ may be enhanced during stressed syllables. Implications
relative to aspects of speech production and clinical practice are discussed.
PMID- 9638917
TI - Altered auditory feedback research conditions and situations of everyday life:
comments on Ingham, Moglia, Frank, Costello Ingham, and Cordes (1997)
PMID- 9638918
TI - Psychometric equivalence of recorded spondaic words as test items.
AB - In the determination of the speech-reception threshold (SRT), spondaic words are
assumed to be homogeneous with respect to intelligibility; and the assumption of
equal intelligibility requires that the words be comparable for all signal
levels. Previous attempts to assess the equal intelligibility assumption using
word thresholds as the sole criterion are not an adequate basis for specifying
the equality of intelligibility. In the present study, the recorded spondaic
words (Tillman recording) were analyzed in an attempt to create a more
homogeneous set of spondaic words for future laboratory work. To achieve this
goal, the data reported by Young, Dudley, and Gunter (1982) and data collected in
our laboratory were fitted to a logistic function (psychometric function) from
which a 50% point (threshold) and slope were obtained. To specify their
acoustical parameters, the recorded spondaic words were digitized and the RMS
level and duration of each syllable and word were calculated. None of the RMS or
duration measures were correlated with word thresholds, so no attempt was made to
equate level or duration. On the other hand, when the threshold of each word was
adjusted to equal the mean threshold of the set (n = 36), the dispersion among
word thresholds and slopes was greatly reduced. Further, we recommend that small
sets of "equally intelligible" spondaic words not be used for clinical testing
because set size is a strong factor in determining threshold for spondees (Meyer
& Bilger, 1997; Punch & Howard, 1985).
PMID- 9638919
TI - Hearing loss, control, and demographic factors influencing hearing aid use among
older adults.
AB - Preference for non-use of hearing aids among older adults who are candidates for
amplification remains to be explained. Clinical studies have examined the
contribution of consumer attitudes, behaviors, and life circumstances to this
phenomenon. The present study extends the interests of earlier investigators in
that it examines psychological control tendencies in combination with hearing
loss and demographic variables among older adults who elected to accept
(adherents) or ignore (nonadherents) advice from hearing professionals to acquire
and use hearing aids. One hundred thirty-one individuals participated by
completing measures of hearing, hearing handicap, psychological control,
depression, and ego strength. Participants were asked to provide demographic
information and personal opinions regarding hearing aid use. Adherence group and
gender differences were noted on measures of hearing sensitivity, psychological
control, and demographic factors. Female adherents demonstrated greater hearing
loss and poorer word recognition ability but less hearing handicap, higher
internal locus of control, higher ego strength, and fewer depressive tendencies
than female nonadherents. They reported demographic advantages. Female adherents
assumed responsibility for effective communication. Although male adherents and
nonadherents did not differ significantly demographically, male adherents were
more accepting of their hearing loss, took responsibility for communication
problems, and found hearing aids less stigmatizing. Implications for clinical
practice and future clinical investigations are identified and discussed. Results
are expected to be of interest to clinicians, clinical investigators, and health
care policymakers.
PMID- 9638920
TI - Functional magnetic resonance imaging measures of blood flow patterns in the
human auditory cortex in response to sound.
AB - Functional Magnetic Resonance Imaging (fMRI) holds exciting potential as a
research and clinical tool for exploring the human auditory system. This
noninvasive technique allows the measurement of discrete changes in cerebral
cortical blood flow in response to sensory stimuli, allowing determination of
precise neuroanatomical locations of the underlying brain parenchymal activity.
Application of fMRI in auditory research, however, has been limited. One problem
is that fMRI utilizing echo-planar imaging technology (EPI) generates intense
noise that could potentially affect the results of auditory experiments. Also,
issues relating to the reliability of fMRI for listeners with normal hearing need
to be resolved before this technique can be used to study listeners with hearing
loss. This preliminary study examines the feasibility of using fMRI in auditory
research by performing a simple set of experiments to test the reliability of
scanning parameters that use a high resolution and high signal-to-noise ratio
unlike that presently reported in the literature. We used consonant-vowel (CV)
speech stimuli to investigate whether or not we could observe reproducible and
consistent changes in cortical blood flow in listeners during a single scanning
session, across more than one scanning session, and in more than one listener. In
addition, we wanted to determine if there were differences between CV speech and
nonspeech complex stimuli across listeners. Our study shows reproducibility
within and across listeners for CV speech stimuli. Results were reproducible for
CV speech stimuli within fMRI scanning sessions for 5 out of 9 listeners and were
reproducible for 6 out of 8 listeners across fMRI scanning sessions. Results of
nonspeech complex stimuli across listeners showed activity in 4 out of 9
individuals tested.
PMID- 9638921
TI - The effects of hearing loss and noise masking on the masking release for speech
in temporally complex backgrounds.
AB - Speech recognition was measured in three groups of listeners: those with
sensorineural hearing loss of (presumably) cochlear origin (HL), those with
normal hearing (NH), and those with normal hearing who listened in the presence
of a spectrally shaped noise that elevated their pure-tone thresholds to match
those of individual listeners in the HL group (NM). Performance was measured in
four backgrounds that differed only in their temporal envelope: steady-state (SS)
speech-shaped noise, speech-shaped noise modulated by the envelope of multi
talker babble (MT), speech-shaped noise modulated by the envelope of single
talker speech (ST), and speech-shaped noise modulated by a 10-Hz square wave
(SQ). Threshold signal-to-noise ratios (SNRs) were typically best in the ST and
especially the SQ conditions, indicating a masking release in those modulated
backgrounds. SNRs in the SS and MT conditions were essentially identical to one
another. The masking release was largest in the listeners in the NH group, and it
tended to decrease as hearing loss increased. In 5 of the 11 listeners in the HL
group, the masking release was nearly identical to that obtained in the NM group
matched to those listeners; in the other 6 listeners, the release was smaller
than that in the NM group. The reduced masking release was simulated best in
those HL listeners for whom the masking release was relatively large. These
results suggest that reduced masking release for speech in listeners with
sensorineural hearing loss can only sometimes be accounted for entirely by
reduced audibility.
PMID- 9638922
TI - Selective visual masking in speechreading.
AB - Using digital video technology, selective aspects of a face can be masked by
identifying the pixels that represent it and then, by adjusting the gray levels,
effectively eliminate that facial aspect. In groups of young adults with normal
vision and hearing, consonant-viseme recognition was measured for closed sets of
vowel-consonant-vowel disyllables. In the first experiment viseme recognition was
measured while the tongue and teeth were masked and while the entire mouth was
masked. The results showed that masking of the tongue and teeth had little effect
on viseme recognition, and when the entire mouth was masked, participants
continued to identify consonant visemes with 70% or greater accuracy in the /a/
and /(ball)/ vowel contexts. In the second experiment, viseme recognition was
measured when the upper part of the face and the mouth were masked and when the
lower part of the face and the mouth were masked. The results showed that when
the mouth and the upper part of the face were masked, performance was poor, but
information was available to identify the consonant-viseme /f/. When the mouth
and the lower part of the face were masked, viseme recognition was quite poor,
but information was available to discriminate the consonant-viseme /p/ from other
consonant visemes.
PMID- 9638923
TI - Children's imitations of intonation contours: are rising tones more difficult
than falling tones?
AB - Perceptual evidence suggests that young children do not imitate adult-modeled
intonation patterns with a rising pitch contour (rising tones) as well as those
with a falling pitch contour (falling tones). To investigate the acoustic basis
of this uneven imitation pattern, 10 4-year-old children were asked to imitate
short sentences with falling and rising tones in 4 sentence contexts called
"intonation groups." The results indicated that the children used more falling
tones than adults in most intonation groups. When the children matched the adult
modeled contour direction (falling or rising), the children's speed of pitch
change was comparable to that of adults in the falling tones of final intonation
groups and in the rising tones of nonfinal groups, but was slower than that of
adults in the complementary environments. In a manner consistent with previously
reported perceptual data, the instrumental findings indicate that rising tones
may be more difficult for 4-year-old children to produce than falling tones. The
results additionally suggest that children's intonation is sensitive not only to
the direction of tonal contours but also to their position in sentence-final
versus nonfinal intonation groups.
PMID- 9638924
TI - Young children's acquisition of the movement aspect in American Sign Language:
parental report findings.
AB - The acquisition of the movement aspect of American Sign Language signs was
examined longitudinally in 9 young children of deaf parents. During monthly home
visits, the parents demonstrated on videotape how their children formed the
different signs in their lexicons. The parents also demonstrated how they formed
or modeled these same signs. Overall, the children correctly produced 61.4% of
the movements that were present in the adult sign models. Although the production
accuracy of the movement aspect of signs did not improve over the course of the
study, the number and complexity of movements produced by the children did
increase as they got older and their vocabularies grew in size. Of the different
sign movements, contacting action was by far the most frequently produced. The
children were also relatively successful in their production of closing action
and downward movement. The order of acquisition for the remaining ASL movements,
however, was quite variable, with the exception that bidirectional movements
tended to be produced more accurately than unidirectional movements. The
relationship between children's early rhythmical motor behaviors and the
development of sign movements is discussed.
PMID- 9638925
TI - Written language comprehension in younger and older adults.
AB - This study examined the effects of text genre and repeated reading on written
language comprehension in younger (M = 21 years) and older (M = 72 years) healthy
adults (N = 54). Participants verified four text-based statements (i.e.,
explicit, implicit, contradictory, and elaborated) after reading expository,
narrative, and procedural texts. Verification accuracy was comparable for both
age groups; however, text genre, statement-type, and repeated reading produced
significant effects. Expository passages, explicit and implicit statements, and
repeated reading yielded superior results. Procedural passages and contradictory
and elaborated statements yielded less accurate results. Statement-types invoked
multiple levels of cognitive representation across text genres and age groups.
Overall, reading time was significantly faster for younger adults, and reading
times were significantly faster for both age groups during the repeated reading
trial. Text genre also influenced reading time, with expository passages read
faster than narrative and procedural passages. These findings suggest the
appreciable influences of text genre and repeated reading on measures of text
processing and comprehension in healthy adults, irrespective of age.
PMID- 9638926
TI - Socioeconomic status and gender influences on children's dialectal variations.
AB - This investigation compares dialect use by African American children differing in
socioeconomic status (SES) and gender. Subjects were 5- and 6-year-old boys (n =
30) and girls (n = 36), who were kindergartners attending schools in the
Metropolitan Detroit area. Comparisons of the amount of dialect in the children's
spontaneous discourse revealed systematic differences relative to SES and gender
in the frequencies but not the forms of dialect in use. Children from lower
income homes, and boys, were more marked dialect users than their middle-class
peers or girls. The sociolinguistic implications of the findings are discussed.
PMID- 9638927
TI - Concurrent and predictive validity of an early language screening program.
AB - The efficacy of screening 2-year-old children for language delay using a parent
report questionnaire was investigated in three studies. The Language Development
Survey (Rescorla, 1989) was mailed to 650 families at the time of their child's
second birthday. Fifty-three percent of the surveys received by parents were
completed and returned. Screening outcomes were then compared, in double-blind
fashion, with the results of comprehensive clinical evaluations at ages 2 (N =
64) and 3 (N = 36). Parents' report of the size of their children's expressive
vocabularies was highly correlated with clinical language measures at age 2.
Children who screened positive performed significantly poorer than children who
screened negative on standardized language tests and on measures taken from
spontaneous conversation. The screening program demonstrated excellent
sensitivity and specificity for identifying language delay at age 2 but somewhat
lower levels for predicting developmental status one year later.
PMID- 9638928
TI - The acquisition of Arabic consonants.
AB - This normative study of the acquisition of consonants of Arabic as spoken in
Jordan answered 4 questions: (1) What percentage of children at each of 9 age
levels produced each consonant correctly? (2) What are the ages of customary
production, mastery, and acquisition for each phoneme? (3) Does accuracy of
consonants within sound classes vary by position in the word? (4) What are the
differences in ages of acquisition between Arabic and English? Samples were
collected from 180 normally developing children between the ages of 2:0 and 6:4.
The percentages of accuracy of both standard and acceptable consonants were
plotted and showed clear developmental trends. Medial consonants were
significantly more accurate than initial and final consonants. The ages of
customary production, acquisition, and mastery of Arabic consonants were similar
to those for English but with notable exceptions that have implications for
description of phonological acquisition. Support for previously proposed
universal sound acquisition sequences was found, but some language-specific
effects were also seen.
PMID- 9638929
TI - Short-term memory and language outcomes after extreme prematurity at birth.
AB - The performance of 26 children (3;0-4;0 years) who were born before 32 weeks
gestation was compared with the performance of 26 full-term children on a range
of short-term memory and language measures. The measures tested vocabulary,
expressive language, phonological short-term memory, and general nonverbal
ability. Preterm children scored more poorly across the full range of measures.
The mildly depressed performance of the preterm group on the short-term memory
and language measures was attributable to the large deficits on these tests shown
by a subgroup of approximately one third of preterm children identified as being
"at risk" for persisting language difficulties using the Bus Story Test (Bishop &
Edmundson, 1987). The findings indicate that preterm birth and associated hazards
may constitute a significant risk factor for specific language impairment in a
sizable minority of children.
PMID- 9638930
TI - Communicative competence as perceived by adults with severe speech impairments
associated with cerebral palsy.
AB - The effects of aided message length (single-word vs. phrase-generated messages)
and partner feedback (presence vs. absence of expanded message repetitions) on
perceptions of the communicative competence of an adult augmentative and
alternative communication (AAC) system user were examined. Subjects consisted of
12 nonambulatory adults with severe speech impairments associated with cerebral
palsy. Four scripted videotaped conversational conditions involving the AAC
system user and a typically speaking partner were employed to manipulate the two
independent variables. A balanced incomplete block design was used. Following
each viewing, subjects completed a questionnaire designed to assess the
communicative competence of the AAC system user. Results indicated that neither
independent variable had an impact on the subjects' ratings of communicative
competence. Findings are compared with those from an earlier investigation, and
clinical implications are discussed.
PMID- 9638931
TI - Acquisition of linguistic and cognitive skills by children with cleft palate.
AB - This study compared the early cognitive and linguistic development of young
children with cleft palate (N = 28) to that of noncleft children (N = 29).
Measures included the Mental scale of the Bayley Scales of Infant Development,
the Minnesota Child Development Inventory, Mean Length of Utterance, and words
acquired by 24 months. Children with cleft palate, although well within the
normal range, performed significantly below the children in the control group on
the Mental Scale of the Bayley Scales of Infant Development, some subscales of
the Minnesota Child Development Inventory, and words acquired by 24 months.
Differences observed in the cognitive development of children with and without
cleft palate were verbal as opposed to nonverbal (i.e., linguistic in nature) and
were related to hearing status at 12 months and velopharyngeal adequacy.
PMID- 9638932
TI - The socioemotional behaviors of children with SLI: Social Adaptation or Social
Deviance?
AB - Two models of the relationship between socioemotional behavior and verbal
abilities are compared: Social Adaptation and Social Deviance. The socioemotional
integrity of 17 children with specific language impairment (SLI) and 20
unaffected children who were age-matched (AM) was examined using the Child
Behavior Checklist (CBCL) and the Teacher's Report Form (TRF) at kindergarten and
first grade. All CBCL and TRF syndrome scale means for both groups were within
normal limits. Significant group x respondent interaction effects were observed;
teachers, and not parents, rated the children with SLI as having more social and
internalizing behavioral problems than their AM peers. Significant differences
between groups were restricted to internalizing, social, and attention problems.
Very little congruence or stability over time was observed in the clinical
ratings. The outcomes support a Social Adaptation Model of socioemotional
behavior and language impairment. Implications for the clinical management of
children with SLI are discussed.
PMID- 9638933
TI - Deficits in finite verb morphology: some assumptions in recent accounts of
specific language impairment.
AB - The grammatical morphology deficits common in children with specific language
impairment (SLI) are characterized in some models as linguistic deficits. Such
models must assume some mechanism for correct productions of finite verb forms.
Three such assumptions were tested by analyzing speech samples from 18 children
with SLI (aged 3 years 6 months to 6 years 9 months). Assumption 1, that
nonfinite forms are used consistently until replaced by memorized finite forms,
was tested by examining the distribution of verb types in present third-person
singular and noun types in present third-person singular contractible copula
contexts. Significantly more word types than expected were inflected
inconsistently. Both Assumption 2, that finite and nonfinite verb forms are
memorized but used indiscriminately, and Assumption 3, that affixation rules are
applied indiscriminately, predict random use of finite forms. This prediction was
not supported.
PMID- 9638934
TI - High sensitivity analysis of proteins and peptides by capillary electrophoresis
tandem mass spectrometry: recent developments in technology and applications.
AB - Analytical biochemistry, in particular the analysis of regulatory proteins that
control biological systems and pathways, is dependent on methods of ever
increasing sensitivity. Capillary electrophoresis (CE) has long been recognized
as an ultrasensitive analytical technique. In spite of the high sensitivity, CE
has not penetrated protein discovery research as a standard analytical method. In
this review article we summarize recent technical developments which have
significantly enhanced CE as a tool for the analysis of trace amounts of
proteins. Specifically, we review recent advances in the development and
application of capillary electrophoresis-mass spectrometry (CE-MS) and on-line
analyte concentration techniques, and introduce the emerging field of
microfluidics as a front end to mass spectrometry (MS).
PMID- 9638935
TI - Database searching using mass spectrometry data.
AB - Large-scale DNA sequencing is creating a sequence infrastructure of great benefit
to protein biochemistry. Concurrent with the application of large-scale DNA
sequencing to whole genome analysis, mass spectrometry has attained the
capability to rapidly, and with remarkable sensitivity, determine weights and
amino acid sequences of peptides. Computer algorithms have been developed to use
the two different types of data generated by mass spectrometers to search
sequence databases. When a protein is digested with a site-specific protease, the
molecular weights of the resulting collection of peptides, the mass map or
fingerprint, can be determined using mass spectrometry. The molecular weights of
the set of peptides derived from the digestion of a protein can then be used to
identify the protein. Several different approaches have been developed. Protein
identification using peptide mass mapping is an effective technique when studying
organisms with completed genomes. A second method is based on the use of data
created by tandem mass spectrometers. Tandem mass spectra contain highly specific
information in the fragmentation pattern as well as sequence information. This
information has been used to search databases of translated protein sequences as
well as nucleotide databases such as expressed sequence tag (EST) sequences. The
ability to search nucleotide databases is an advantage when analyzing data
obtained from organisms whose genomes are not yet completed, but a large amount
of expressed gene sequence is available (e.g., human and mouse). Furthermore, a
strength of using tandem mass spectra to search databases is the ability to
identify proteins present in fairly complex mixtures.
PMID- 9638936
TI - Sample handling for proteome analysis.
AB - The main factor limiting the sensitivity range for the identification of proteins
isolated by two-dimensional (2-D) electrophoresis is sample handling: protein
detection limits on the gel, losses during extraction and digestion, as well as
interference of gel contaminants and detergents with the mass spectrometry (MS)
detection increasing background noise. At the one hundred picomole level, losses
are fairly negligible but when the amounts drop below 1 picomole (and
subfemtomole peptide detection limits have been reported recently by MS), the
losses become a critical point. In order to extend proteome analysis to include
very low copy number proteins, methods must be developed to minimize losses and
handling steps, maximize digestion and extraction yields, as well as to lower
chemical noise. We present several methods that we have developed in our
laboratory to: (i) increase the amount of material available in a sodium dodecyl
sulfate (SDS)-free form which does not require staining, (ii) increase protein
extraction and digestion yields and lower the contamination by autoproteolytic
products, and (iii) allow direct modification of the peptide mixture to generate
sequence tags.
PMID- 9638937
TI - A peptide concentration and purification method for protein characterization in
the subpicomole range using matrix assisted laser desorption/ionization
postsource decay (MALDI-PSD) sequencing.
AB - We here describe the use of added reversed-phase chromatographic beads to
concentrate peptides from highly diluted solutions. In the procedure developed,
peptide-bead suspensions are dried under vacuum to complete dryness; peptides are
subsequently eluted in a small volume of matrix-assisted laser
desorption/ionization (MALDI)-matrix containing organic/aqueous solvent and
transferred to a MALDI-target for mass analysis. We show that by using this bead
peptide concentration procedure, low femtomole amounts of peptides are
efficiently concentrated, up to 1000 times, to volumes smaller than 0.7 microL.
We have used this concentration procedure in combination with MALDI-post-source
decay analysis to identify subpicomole amounts of proteins present in
polyacrylamide gels. Furthermore, we show that the bead-peptide concentration
method can be elegantly used to clean up samples contaminated with high
concentrations of substances normally deleterious to MALDI-mass spectrometry (MS)
experiments. We have found additionally that the bead-peptide concentration
procedure can be successfully used to store low femtomole amounts of peptide for
prolonged periods of time without severe losses of peptide material. This bead
peptide concentration procedure therefore seems to be a simple and convenient
step in the MALDI-MS sample preparation process.
PMID- 9638938
TI - Peptide mass fingerprint sequence coverage from differently stained proteins on
two-dimensional electrophoresis patterns by matrix assisted laser
desorption/ionization-mass spectrometry (MALDI-MS).
AB - Identification of proteins separated by two-dimensional electrophoresis (2-DE) is
a necessary task to overcome the purely descriptive character of 2-DE and a
prerequisite to the construction of 2-DE databases in proteome projects. Matrix
assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has a
sensitivity for peptide detection in the lower fmol range, which should be
sufficient for an analysis of even weakly silver-stained protein spots by peptide
mass fingerprinting. Unfortunately, proteins are modified by the silver staining
procedure, leading to low sequence coverage. Omission of glutaraldehyde increased
the sequence coverage, but this improved sequence coverage is still clearly below
the sequence coverage starting with Coomassie Brilliant Blue (CBB) R-250-stained
spots. Other factors additionally seem to modify proteins during silver staining.
By decreasing the protein amount, the advantage of very sensitive detection on
the gel is lost during identification, because the resulting low sequence
coverage is not sufficient for secure identification. Low-quantity proteins can
be identified better starting with CBB G-250 or Zn-imidazol-stained proteins. In
contrast, for high-quantity CBB R-250-stained spots, a sequence coverage of up to
90% can be obtained by using only one cleaving enzyme, and up to 80% was reached
for medium-quantity spots after combination of tryptic digest with Asp-N- and Glu
C digest.
PMID- 9638939
TI - Additional possible tools for identification of proteins on one- or two
dimensional electrophoresis.
AB - Additional, essentially chemical, identification methods of proteins in
polyacrylamide gel electrophoresis are described. Two cleavages of peptide bonds
were used at the C-side of aspartic acid with a 0.2% pentafluoropropionic acid
(PFPA) aqueous vapor at 90 degrees C for 4-16 h, and the N-side of
serine/threonine with an S-ethyl trifluorothioacetate vapor at 50 degrees C for 6
24 h. The products were analyzed by mass spectrometry-peptide mass
fingerprinting. A new type of C-terminal sequencing at multisites of protein was
introduced. An aqueous vapor of 90% PFPA at 90 degrees C for 2-16 h provided
cleavages at the C-side of aspartic acid and the N-side of serine/threonine and
simultaneous successive truncation at the C-termini of the cleaved fragments. The
product resulted in C-terminal sequences at multisites in proteins by mass
spectrometric analysis. The following chemical deblocking methods were used.
Anhydrous hydrazine vapor at -5 degrees C for 8 h deblocked the N-formyl group,
and the vapor at 20 degrees C for 4 h deblocked pyrrolidone carboxylate. N
acetylserine/threonine was deblocked by aqueous vapor of 75% PFPA at 50 degrees C
for 1 h, followed by reaction with p-sulfophenylisothiocyanate at pH 6.0. These
methods were applied to a variety of protein spots on polyacrylamide gels. A new
stepwise C-terminal sequencing of protein from polyacrylamide gels is also
described.
PMID- 9638940
TI - Identification of gel-separated proteins by liquid chromatography-electrospray
tandem mass spectrometry: comparison of methods and their limitations.
AB - We have compared several different experimental systems currently in use in our
laboratory for protein identification by high performance liquid chromatography
electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) after sodium
dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The efficiency of
peptide recovery from trypsin-digested gel bands or electroblotted membrane
slices was examined using 35S-labeled yeast proteins, and was found to be in
excess of 80%. A dilution series of two standard proteins, bovine serum albumin
(BSA) and carbonic anhydrase (CA), was analyzed by HPLC-ESI-MS/MS to determine
what amount of protein could be loaded onto a gel and successfully identified, a
measure we refer to as the practical detection limit. We were able to identify
both standards at the 500 ng level in samples prepared from gel slices, using
either a regular spray or a flow-split microspray HPLC-MS interface system. In
samples prepared from membrane pieces, carbonic anhydrase was also identified at
the 500 ng level, while bovine serum albumin could only be identified in samples
of more than 1000 ng. In general, protein identification was slightly better in
samples prepared from gels rather than membranes. A dilution series of lesser
amounts of the same standard proteins was also analyzed using a gradient
capillary LC system and we were able to successfully identify 50 ng of carbonic
anhydrase and 100 ng of BSA.
PMID- 9638941
TI - Capillary column chromatography improves sample preparation for mass
spectrometric analysis: complete characterization of human alpha-enolase from two
dimensional gels following in situ proteolytic digestion.
AB - Two-dimensional polyacrylamide gel electrophoresis (2-DE) in combination with
mass spectrometry is an extremely powerful tool for characterizing complex
mixtures of proteins. In many cases, the success of this approach relies upon the
ability to recover peptides at high concentrations and free of interfering
artifacts from in-gel and/or on-membrane enzymatic digests. In previous studies,
we demonstrated that capillary or microcolumn (< 350 microm ID) reversed-phase
high performance liquid chromatography (RP-HPLC) is a powerful microseparation
technique for proteins and peptides (Moritz, R. L. and Simpson, R. J., J.
Chromatogr. 1992, 599, 119-130). Here we evaluate various capillary column RP
HPLC/mass spectrometric approaches for identifying and characterizing 2-DE
resolved proteins. For these studies, stable and efficient 0.20 mm and 0.32 mm
internal diameter (ID) fused-silica columns with hydrophilic polyvinylidene
difluoride (PVDF) frits were fabricated and slurry packed with 7 microm
spherical, 300 A pore size, C8 bonded phase silica particles. We show that
capillary column chromatography is a rapid and efficient desalting/concentrating
(ON/OFF) technique for sample cleanup prior to protein identification by peptide
mass fingerprinting using matrix-assisted laser desorption ionization (MALDI)
time-of-flight mass spectrometry. While marginally more peptide mass information
can be obtained by stepped elution of the peptide mixture with increasing
concentrations of organic solvent, best results were obtained by fractionation of
the peptide mixture using a linear 60 min gradient. One salient feature of this
study was the observation that, in contrast to the stepped elution and gradient
approaches, the ionization of peptide T1 (m/z 2402.2 SGETEDTFIADLVV(PeCys)TGQIK)
was almost completely suppressed using the ON/OFF approach. Maximal amino acid
sequence coverage, a necessary prerequisite for complete characterization of a
protein, was accomplished using a capillary column (0.2 mm ID) directly coupled
with an electrospray ionization (ESI) ion-trap tandem mass spectrometer. For
example, from an in situ tryptic digest of alpha-enolase isolated by 2-DE from
the human breast carcinoma cell line MDA-MB231, 71% of the amino acid sequence
was obtained. In addition to identifying two possible N-terminal acetylated alpha
enolase variants, Asn153Asp and Ile152Asp/Asn153Ile, the tandem mass
spectrometric data revealed the presence of a number of process-induced
modifications of alpha-enolase such as methionine oxidation and cysteine
amidoethylation.
PMID- 9638942
TI - Optimization of capillary chromatography ion trap-mass spectrometry for
identification of gel-separated proteins.
AB - The current paradigm for protein identification using mass spectrometric derived
peptide-mass and fragment-ion data employs computer algorithms which match
uninterpreted or partially interpreted fragment-ion data to sequence databases,
both protein and translated nucleotide sequence databases. Nucleotide sequence
databases continue to grow at a rapid rate for some species, providing an
unsurpassed resource for protein identification in those species. Ion-trap mass
spectrometers with their ability to rapidly generate fragment-ion spectra in a
data-dependent manner with high sensitivity and accuracy has led to their
increased use for protein identification. We have investigated various parameters
on a commercial ion trap-mass spectrometer to enhance our ability to identify
peptides separated by capillary reversed phase-high performance liquid
chromatography (RP-HPLC) coupled on-line to the mass spectrometer. By
systematically evaluating the standard parameters (ion injection time and number
of microscans) together with selection of multiple ions from the full mass range,
improved tandem mass spectrometry (MS/MS) spectra were generated, facilitating
identification of proteins at a low pmol level. Application of this technology to
the identification of a standard protein and an unknown from an affinity-enriched
mixture are shown.
PMID- 9638943
TI - Rapid identification of comigrating gel-isolated proteins by ion trap-mass
spectrometry.
AB - In the search for novel nuclear binding proteins, two bands from a sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel were analyzed and each
was found to contain a number of proteins that subsequently were identified by
tandem mass spectrometry (MS/MS) on a quadrupole ion trap instrument. The bands
were digested with trypsin in situ on a polyvinylidene difluoride (PVDF) membrane
following electroblot transfer. Analysis of a 2.5% aliquot of each peptide
mixture by matrix assisted laser desorption/ionization-mass spectrometry (MALDI
MS) followed by an initial database search with the peptide masses failed to
identify the proteins. The peptides were separated by reversed-phase capillary
high performance liquid chromatography (HPLC) in anticipation of subsequent Edman
degradation, but mass analysis of the chromatographic fractions by MALDI-MS
revealed multiple, coeluting peptides that precluded this approach. Selected
fractions were analyzed by capillary HPLC-electrospray ionization-ion trap mass
spectrometry. Tandem mass spectrometry provided significant fragmentation from
which full or partial sequence was deduced for a number of peptides. Two stages
of fragmentation (MS3) were used in one case to determine additional sequence.
Database searches, each using a single peptide mass plus partial sequence,
identified four proteins from a single electrophoretic band at 45 kDa, and four
proteins from a second band at 60 kDa. Many of these proteins were derived from
human keratin. The protein identifications were corroborated by the presence of
multiple matching peptide masses in the MALDI-MS spectra. In addition, a novel
sequence, not found in protein or DNA databases, was determined by interpretation
of the MS/MS data. These results demonstrate the power of the quadrupole ion trap
for the identification of multiple proteins in a mixture, and for de novo
determination of peptide sequence. Reanalysis of the fragmentation data with a
modified database searching algorithm showed that the same sets of proteins were
identified from a limited number of fragment ion masses, in the absence of mass
spectral interpretation or amino acid sequence. The implications for protein
identification solely from fragment ion masses are discussed, including
advantages for low signal levels, for a reduction of the necessary interpretation
expertise, and for increased speed.
PMID- 9638944
TI - Analyzing glycoproteins separated by two-dimensional gel electrophoresis.
AB - Two-dimensional (2-D) electrophoresis is the preferred method for separating the
glycoforms of proteins. The isoforms usually present as 'trains' of spots in the
first dimension and may also differ in molecular weight. The primary goal for
analyzing the carbohydrate content of glycoprotein spots is to understand the
'rules' which govern the migration of glycoproteins in 2-D electrophoresis. These
rules can then be used to produce predictive vectors to interpret changes in
glycosylation patterns. Techniques for the analysis of oligosaccharides released
from glycoproteins which have been electroblotted to PVDF membrane after one
dimensional (1-D) and 2-D preparative gel electrophoresis are described. The
oligosaccharides are removed enzymatically (PNGase F of N-linked
oligosaccharides) or chemically (beta-elimination of O-linked oligosaccharides)
and separated by high performance anion exchange chromatography (HPAEC-PAD) and
identified by electrospray ionization mass spectrometry (ESI-MS) or analyzed
directly by ESI-MS. After enzymic removal of the N-linked oligosaccharides the
protein spots can be further analyzed by Edman sequence tagging for
identification and quantitation of the protein and by acid hydrolysis for
monosaccharide analysis of the O-linked oligosaccharides. These approaches have
been proved on 1-D PAGE electroblotted bovine fetuin and human glycophorin A and
then used to analyze two abundant proteins which separate as glycoforms on 2-D
PAGE preparative narrow range (pH 4.5-5.5) blots of human plasma: alpha2-HS
glycoprotein (human fetuin) and alpha1-antitrypsin (alpha1-protease inhibitor).
It is apparent that both the macroheterogeneity (site occupation) and
microheterogeneity (diversity of structures) of the glycosylation contribute to
the separation of protein isoforms in 2-D PAGE.
PMID- 9638945
TI - The identification of peptide modifications derived from gel-separated proteins
using electrospray triple quadrupole and ion trap analyses.
AB - Microspray tandem mass spectrometry (MS/MS) in combination with database search
routines has become a powerful tool for the identification of proteins from
femtomole amounts of material following gel electrophoresis and in-gel digestion
procedures. However, artifactual modification of susceptible residues can arise
during gel electrophoresis, leading to unexpected peptide mass shifts during mass
analysis. Consequently, collision-induced dissociation (CID) spectra generated
from these derivatized peptides can defy direct interpretation by automated
database search routines and remain unidentified. Here, we evaluate the MS/MS
spectra of peptides carrying oxidized derivatives of tryptophane and methionine
residues, and various modifications of cysteine. We demonstrate that certain of
these modifications generate characteristic fragmentation patterns or
"fingerprints", during CID analysis, the knowledge of which can facilitate the
interpretation of the spectra. We will show that these signature fragment ions
are predominantly produced during the CID analysis of singly charged ions
although they can be observed in the MS/MS spectra of the doubly charged species
as well. In other cases, the CID spectrum lacks a characteristic fingerprint and
the modification remains silent. However, CID spectra of related peptides,
differing only by their modifications, are similar and all or part of the
fragment ion spectra will have shifted by a discreet mass, which facilitates the
identification of the modified residue. At the same time, the comparison of
related spectra can prevent misinterpretations such as the assignment of a
residue mass to the wrong amino acid or a neutral loss fragment ion to a gamma-
or b-ion.
PMID- 9638946
TI - Protein identification using mass spectrometric information.
AB - In an effort to gain an understanding of the value of the information in
different mass spectrometric measurements for protein identification, the genome
of Saccharomyces cerevisiae was studied in silico. We calculate how constraining
the knowledge of the mass of a proteolytic peptide is as a function of mass and
mass accuracy. We also assess the value for protein identification of additional
information concerning a proteolytic peptide, including the presence or absence
of a given amino acid, the number of exchangeable hydrogens, the N-terminal
sequence, and the masses of mass spectrometrically produced fragment ions.
Knowledge of the relative value of these different constraints is useful in the
design of efficient protein identification experiments. Finally, we describe a
software tool, PepFrag, for searching protein and DNA sequence databases that can
use different types of mass spectrometric information to restrict the search.
PMID- 9638947
TI - Two-dimensional electrophoresis of human placental mitochondria and protein
identification by mass spectrometry: toward a human mitochondrial proteome.
AB - Owing to the complexity of higher eukaryotic cells, characterization of a
complete proteome is likely to be difficult to achieve. However, advantage can be
taken of the cell compartmentalization to build organelle proteomes, which can
moreover be viewed as specialized tools to study specifically the biology and
"physiology" of the target organelle. Within this frame, we report here the
construction of the human mitochondrial proteome, using placenta as the source
tissue. Protein identification was carried out mainly by peptide mass
fingerprinting, but other methods were also used (N-terminal microsequencing,
blotting). The optimization steps in two-dimensional (2-D) electrophoresis needed
for proteome research are discussed. However, the relative paucity of data
concerning mitochondrial proteins is still the major limiting factor in building
the corresponding proteome, which should be a useful tool for researchers working
on human mitochondria and their deficiencies.
PMID- 9638948
TI - Identification of phosphorylated proteins from thrombin-activated human platelets
isolated by two-dimensional gel electrophoresis by electrospray ionization-tandem
mass spectrometry (ESI-MS/MS) and liquid chromatography-electrospray ionization
mass spectrometry (LC-ESI-MS).
AB - Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful tool
to separate complex protein mixtures including whole cell lysates. In combination
with immunoblotting techniques or radioactive labeling techniques it is a fast
and convenient way to demonstrate the presence of certain proteins or protein
modifications. With the development of extremely sensitive analytical techniques
such as matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS)
or electrospray ionization (ESI)-MS, it has become possible to use 2-D gels not
only as an analytical but also as a preparative tool. Starting with a number of
spots excised from 2-D gels, a protein can be identified using different
strategies involving enzymatic cleavage of the protein in the gel matrix, elution
of the resulting peptides and analysis of these peptides by mass spectrometry.
The obtained peptide mass fingerprint or fragment ion spectra from peptides can
be used to screen protein or nucleic acid databases in order to identify the
protein. We have used the techniques described above to identify proteins from
human platelets which change their phosphorylation state following activation of
platelets by thrombin. Platelets were radioactively labeled with
[32P]orthophosphate and stimulated. Several protein spots in the observed range
of 10-80 kDa and an isoelectric point of 3-10 showed a significant increase or
decrease in phosphorylation. We present the results from the investigation of a
spot group representing different isoforms and phosphorylation states of myosin
light chain.
PMID- 9638949
TI - Correlation of acidic and basic carrier ampholyte and immobilized pH gradient two
dimensional gel electrophoresis patterns based on mass spectrometric protein
identification.
AB - Separation of proteins on either carrier ampholyte-based or immobilized pH
gradient-based two-dimensional (2-D) gels gives rise to electrophoretic patterns
that are difficult to compare visually. In this paper we have used matrix
assisted laser desorption/ionization mass spectrometry (MALDI-MS) to determine
the identities of 335 protein spots in these two 2-D gel systems, including a
substantial number of basic proteins which had never been identified before.
Proteins that were identified in both gel systems allowed us to cross-reference
the gel patterns. Vector analysis of these cross-references demonstrated that
there is no obvious pattern by which the mobility of a protein in one gel system
can be used to predict its mobility in the other. Thus, as laboratories adopt the
immobilized pH gradient-based 2-D gel systems, the only reliable means of
translating the data gained with the carrier ampholyte-based gel system is to
positively identify the proteins in both 2-D systems.
PMID- 9638950
TI - Routine identification of proteins from sodium dodecyl sulfate-polyacrylamide gel
electrophoresis (SDS-PAGE) gels or polyvinyl difluoride membranes using matrix
assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF
MS).
AB - As the resource laboratory for Rockefeller University our emphasis continues to
be on methodology development for the routine analysis of low abundance proteins
isolated from native sources. In the past ten years, gel electrophoresis of
proteins has become the method of choice for the preparation of microgram and
submicrogram quantities of protein for primary structural characterization, and
over 95% of the samples submitted for protein identification are either in a gel
or bound to polyvinyl difluoride membranes (PVDF). As such, we employ multiple
microanalytical approaches encompassing Edman sequence degradation, amino acid
and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass
spectrometric analysis to provide an integrated protein characterization of such
samples. Here we describe the two major services we employ when providing protein
identification from in-gel or PVDF-bound proteins.
PMID- 9638951
TI - Use of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC
ESI-MS/MS) for routine identification of enzymatically digested proteins
separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
AB - Automated liquid chromatography-electrospray ionization-tandem mass spectrometry
(LC-ESI-MS/MS) analysis of >100 tryptic digests carried out on sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separated, Coomassie Blue
stained proteins that were prepared by >50 different laboratories demonstrates
that a commercial electrospray/quadrupole ion trap mass spectrometer and the
tandem mass correlation algorithm developed by Eng et al. (Am. Soc. Mass
Spectrom. 1994, 5, 976-989) provide an extremely robust and facile approach to
routine protein identification. By requiring a minimum of two significant matches
to peptides that would be predicted to be produced by the protease that was used,
low pmol levels of proteins can be identified with high confidence while
minimizing the probability of identifying the protease itself and/or the
ubiquitous contaminant, keratin. Hence, in only 7% of the digests analyzed was
keratin identified and in only 5% of the digests analyzed was the protease itself
identified. In contrast, 58% of the analyzed samples were identified and, in many
instances, multiple proteins were identified in the same sample. Although the
median amount of digest analyzed was 6.1 pmol, the limit of sensitivity (as the
instrument is configured with a flow rate of 4 microL/min) appears to be at the
500 fmol level. Since one of the primary reasons for not identifying a sample is
that its sequence is not yet in the database searched, the utility of an LC MS/MS
approach to protein identification will certainly increase in the future as the
sequences of more genomes are completed.
PMID- 9638952
TI - The emotional motor system in relation to the supraspinal control of micturition
and mating behavior.
PMID- 9638953
TI - Premature ejaculation and serotonergic antidepressants-induced delayed
ejaculation: the involvement of the serotonergic system.
AB - Premature ejaculation has generally been considered a psychosexual disorder with
psychogenic aetiology. Although still mainly treated by behavioural therapy, in
recent years double-blind studies have indicated the beneficial effects of some
of the serotonergic antidepressants (SSRIs) in delaying ejaculation. We describe
here the neurophysiology and the peripheral neuroanatomy of ejaculation and
provide a review of the involvement of serotonin in the central nervous system in
relation to serotonergic nuclei and their projections. A hypothesis of the role
of 5-HT1A and 5-HT2C receptors in premature ejaculation is postulated.
PMID- 9638954
TI - The central nervous system control of micturition in cats and humans.
AB - Recent findings concerning the central control of micturition in cats are
compared to findings obtained from dynamic imaging studies in humans. In the cat,
three areas in the brainstem and diencephalon are specifically implicated in the
control of micturition: (1) Barrington's nucleus or the pontine micturition
center in the dorsomedial pontine tegmentum directly excites bladder motoneurons
and indirectly inhibits, via inhibitory interneurons in the medial sacral cord,
urethral sphincter motoneurons; (2) the periaqueductal grey receiving bladder
filling information; and (3) the pre-optic area of the hypothalamus possibly
involved in determining the beginning of micturition. According to PET-scan
studies, in humans the same supraspinal regions are active during micturition. In
the cat another area, located in the ventrolateral pontine tegmentum and is
called the L-region, which controls the motoneurons of the pelvic floor,
including the external urethral sphincter. This region might be considered as the
pontine storage center. In humans the L-region is especially active in volunteers
who tried but did not succeed to micturate. The results suggest that in cats and
humans at the brainstem and diencephalic levels micturition is organized in the
same way.
PMID- 9638955
TI - Developmental and injury induced plasticity in the micturition reflex pathway.
AB - The storage and periodic elimination of urine are dependent upon neural circuits
in the brain and spinal cord that co-ordinate the activity of the urinary
bladder, the urethra and the striated urethral sphincter. This study utilized
anatomical, electrophysiological and pharmacological techniques to examine: (1)
the organization of the parasympathetic excitatory reflex mechanisms that control
the urinary bladder of the rat and the cat; and (2) the changes in these reflexes
during postnatal development and after spinal cord injury. In normal adult cats
and rats, the parasympathetic excitatory input to the bladder is dependent upon a
spinobulbospinal reflex pathway that is activated by myelinated (Adelta) bladder
afferents and that passes through an integrative center (the pontine micturition
center, PMC) in the rostral brain stem. Transneuronal tracing studies using
pseudorabies virus as well as physiological methods have revealed that the PMC is
located in close proximity to the locus coeruleus. Single unit recordings
indicate that neurons in the PMC respond to afferent input from the bladder and
are excited prior to or during reflex bladder contractions. Glutamic acid is the
major excitatory transmitter in the micturition reflex pathway. Glutamatergic
transmission which is mediated by AMPA/kainate and NMDA receptors can be
modulated by a variety of other transmitters. In neonatal animals, a spinal
micturition reflex is activated by somatic afferent fibers from the perigenital
region. This reflex is suppressed during postnatal development, but can be
unmasked in adult animals following spinal cord injury. Spinal injury also causes
the emergence of a spinal bladder-to-bladder reflex which in the cat is activated
by capsaicin-sensitive C-fiber bladder afferents. Patch clamp studies in spinal
cord slice preparations indicate that developmental and spinal cord injury
induced plasticity in sacral parasympathetic reflex pathways is due in part to
alterations in glutamatergic excitatory transmission between interneurons and
preganglionic neurons. Changes in the electrical properties of bladder afferent
pathways may also contribute to the reorganization of bladder reflexes in
paraplegic animals.
PMID- 9638956
TI - Neuromodulation: urodynamic effects of sacral (S3) spinal nerve stimulation in
patients with detrusor instability or detrusor hyperflexia.
AB - The aim of this study was to determine the urodynamic effects of sacral (S3)
nerve stimulation in patients with urge incontinence due to detrusor overactivity
which has been refractory to conservative treatment. A total of 24 patients with
idiopathic detrusor instability and five with neurogenic hyperreflexia were
studied urodynamically before and 6 months after a permanent S3 foramen electrode
implant. The urodynamic studies at follow-up were done with the stimulus on.
Clinically, the average voiding frequency, the number of leakage episodes and pad
use per 24 h decreased significantly. Improvement in several urodynamic
parameters was noted. In the idiopathic as well as in the neurogenic group, the
correlation between symptomatic and urodynamic improvement was incomplete.
Neuromodulation leads to improvement of several urodynamic parameters in patients
with urge incontinence due to detrusor overactivity which has been refractory to
conservative treatment and appears to be a valuable treatment option in these
patients.
PMID- 9638957
TI - Clinical studies of cerebral and urinary tract function in elderly people with
urinary incontinence.
AB - Brain and urinary tract function have been studied in a group of 128 geriatric
patients with established urinary incontinence. Median age was 79 years. About
half suffered from dementia. A group of 27 continent patients of similar age and
cognitive status was used in some comparisons. It was expected that impaired
voluntary control of voiding (urge incontinence) would be associated with
particular aspects of cognitive impairment and dysfunction of specific regions of
the brain. Comprehensive investigations, including 24 h monitoring of
incontinence, videourodynamic testing, cognitive testing and SPECT brain
scanning, demonstrated that genuine urge incontinence could be proven in half of
the patients and was frequently accompanied by reduced sensation of bladder
filling, especially in males. Genuine urge incontinence with reduced bladder
filling sensation led to greater urine loss than other types of incontinence.
Overall, cognitive function was slightly more impaired in patients with genuine
urge incontinence, but the strongest and most specific association was with
impaired temporal orientation. Genuine urge incontinence with reduced bladder
filling sensation was associated with global underperfusion of the cerebral
cortex and more specifically, with underperfusion of the frontal areas of the
brain, especially on the right. These results are consistent with PET scan
observations of Blok et al. (Brain 1997;20:112-121), which show that areas in the
right anterior cingulate gyrus and right inferior frontal gyrus are involved in
voluntary voiding of normal males.
PMID- 9638958
TI - Sensory and motor components of reproductive behavior: pathways and plasticity.
AB - Reproductive behavior in most mammalian species consists of a highly stereotyped
pattern of movements, is elicited by specific sensory stimuli and is sex steroid
dependent. The present paper describes a concept of the pathways in the midbrain,
brainstem and spinal cord which control the receptive posture of the female cat.
The midbrain periaqueductal gray (PAG), which is an important structure in the
Emotional Motor System (EMS), receives direct input from a distinct group of
neurons in the dorsal horn of the lumbosacral cord. This cell group overlaps with
the location of pelvic and to lesser extent, pudendal nerve primary afferents,
which convey information from the pelvic viscera and sex organs to the central
nervous system. The PAG, in turn, controls various motor components of female
receptive behavior using different pathways. For example, immobility, which is
one of the characteristics of receptive behavior, might be mediated by a diffuse
pathway from the PAG, via the ventral part of the medial medullary tegmentum, to
all parts of the spinal ventral horn. More specific components, such as hindlimb
treading, lateral deviation of the tail and elevation of the lower back, are
thought to be controlled by a circumscribed projection from the PAG to the
nucleus retroambiguus (NRA). The NRA is a group of interneurons at the transition
between brainstem and spinal cord and projects directly to distinct lumbosacral
motoneuronal cell groups, which innervate muscles that are likely to be involved
in the female receptive posture. Estrogen induces axonal sprouting of the NRA
lumbosacral pathway in adult female cats, which explains why female cats only
display receptive behavior when estrogen levels are high.
PMID- 9638959
TI - Mapping of neural and signal transduction pathways for lordosis in the search for
estrogen actions on the central nervous system.
AB - Estrogen can act on the brain to regulate various biological functions and
behavior. In attempts to elucidate the estrogen action, the rodent female
reproductive behavior, lordosis, was used as a model. Lordosis is an estrogen
dependent reflexive behavior and, hence, is mediated by discrete neural pathways
that are modulated by estrogen. Therefore, a strategy of mapping the pathways,
both neural and biochemical, and examining them for estrogen effect was used to
localize and subsequently analyze the central action of estrogen. Using various
experimental approaches, an 'inverted Y-shaped' neural pathway both sufficient
and essential for mediating lordosis was defined. The top portion is a descending
pathway conveying the permissive estrogen influence which originated from
hypothalamic ventromedial nucleus relayed via midbrain periaqueductal grey down
to medullary reticular formation, the top of the spino-bulbo-spinal reflex arc at
the bottom. This estrogen influence alters the input-output relationship,
shifting the output toward more excitation. With this shift in output, estrogen
can enable the otherwise ineffective lordosis-triggering sensory stimuli to
elicit lordosis. In the ventromedial nucleus, the origin of the estrogen
influence, a multidisciplinary approach was used to map intracellular signaling
pathways. A phosphoinositide pathway involving a specific G protein and the
activation of protein kinase C was found to be involved in the mediation of
lordosis as well as a probable target of the permissive estrogen action. The
action of estrogen on this signal transduction pathway, a potentiation, is
consistent with and, hence, may be an underlying mechanism for the estrogen
influenced shift toward excitation. Thus, further investigation on this specific
signal transduction pathway should be helpful in elucidating the action of
estrogen on the brain.
PMID- 9638960
TI - Neural activation following sexual behavior in the male and female rat brain.
AB - Neural activation following sexual behavior was studied in the male and female
rat brain, using Fos-immunoreactivity (Fos-IR) as a measure. In accordance with
the available literature, we observed increased expression of c-fos in the medial
preoptic nucleus (MPN), in the posteromedial subdivision of the bed nucleus of
the stria terminalis, in the posterodorsal part of the medial amygdala, and in
the caudal thalamus, in the parvicellular part of the subparafascicular nucleus.
After performance of different behavioral elements (anogenital investigation,
mounting, intromission or ejaculation) not only the numbers of Fos-IR neurons
varied considerably, but also their distribution. Especially after ejaculation,
but in females already after intromissions, dense groups of Fos-IR neurons
appeared in specific subdivisions of the areas mentioned above. That these groups
of dense Fos-IR appeared as a result of the ejaculation per se, was assessed by
administrating the 5-HT1A agonist 8-OH-DPAT to the males, whereupon they
ejaculated within a few seconds, without the usual amount of preceding behavioral
elements. Since the pattern of Fos-IR was similar to the normal ejaculation
pattern, we have described the dense activation areas as 'ejaculation-related
clusters'. Our review discusses the stimuli and pathways probably involved in the
observed pattern of Fos-IR and we conclude that the 'deep viscero-genital'
activation, occurring at the moment of ejaculation, running along the pelvic
nerve and ascending from the spinal cord, is most probably responsible. We show
that the location of the Fos-IR neurons in the medial subparafascicular nucleus
perfectly coincides with the location of Galanin-IR fibers, ascending from the
spinal cord. The application of anterograde and retrograde neuroanatomical
tracers into the MPN, in combination with Fos-IR showed that the medial preoptic
nucleus has very specific relationships with the Fos-IR sub-areas, involved in
ejaculation. We conclude that within the larger brain structures involved in
sexual and other social activities, a specific ejaculation-related subcircuit
exists, which may, under normal conditions in the rat, serve a 'sexual-satiety
function'.
PMID- 9638961
TI - Organization and regulation of sexually dimorphic neuroendocrine pathways.
AB - Reproduction depends on the co-ordinated expression of stereotypical behaviors
and precisely timed physiological events, yet the neurobiological mechanisms
underlying the integration of sensory and hormonal information that is crucial to
this process have remained difficult to define. A variety of experimental
approaches has provided compelling evidence that the anteroventral
periventricular nucleus (AVPV) of the preoptic region plays a particularly
important role in the neural control of gonadotropin secretion. It is larger in
female rats, contains high densities of neurons that express receptors for
ovarian steroid hormones and appears to provide direct projections to
gonadotropin releasing hormone neurons in the hypothalamus. Moreover, it receives
inputs from a variety of distinct sensory systems known to influence secretion of
luteinizing hormone from the anterior pituitary. Thus, the AVPV appears to
represent an important nodal point in sexually dimorphic forebrain circuits for
the integration of sensory and hormonal information that influence reproduction.
Examples of neurohumoral integration at the level of functional neural systems,
individual neurons in the AVPV, or at the molecular level have been identified
which provide new insight into how the hypothalamus co-ordinates expression of
sex specific reproductive behaviors with gonadotropin secretion.
PMID- 9638962
TI - Double duty for sex differences in the brain.
AB - Sex differences have been found in the anatomy of brains of a wide variety of
vertebrates including humans. Common lore tells us that sex differences in the
brain cause sex differences in behavior. This review entertains the possibility
that sex differences in the brain may also do the exact opposite. Specifically,
sex differences may allow males and females to display remarkably similar
behaviors, despite major differences in their physiological and hormonal
conditions. First, the difficulties in interpreting the relationship between
structure and function will be illustrated by discussing the role of the sexually
dimorphic medial preoptic area (MPOA) in male sexual behavior and parental
behavior. Second, the sexually dimorphic vasopressin innervation of the brain
will be presented as a system that appears to promote as well as prevent sex
differences in behavior. Finally, basic and clinical aspects of sex differences
in human brains will be discussed.
PMID- 9638963
TI - Comparison of endothelin-1 levels at rest and during exercise between patients
with cardiac syndrome-X and healthy people.
AB - Several previous studies have shown that endothelin-1 (ET 1) plasma levels are
raised in cases of endothelial abnormality and microvascular dysfunction.
Syndrome-X constitutes an important clinical entity characterized by angina-like
pain and normal coronary arteries which is believed to reflect microvascular
dysfunction. The aim of the present study was to investigate the role of ET 1 in
the pathophysiology of the above syndrome. For that purpose the plasma ET 1
concentrations, measured by radioimmunoassay, between 28 X-syndrome patients
(group A) and 10 age-matched normal control subjects (group B) at rest and at the
peak of the exercise testing were compared. We specify that all individuals of
group A were referred to our Department for effort angina and were found to have
normal coronary arteriograms, negative ergonovine and hyperventilation test and
positive exercise test. Our results showed that while at rest ET 1 plasma
concentrations did not differ significantly between the two groups, at the peak
of the exercise test its levels were found to be significantly higher in syndrome
X patients as compared with those of normal subjects (p< 0.001). In addition, in
healthy control subjects ET 1 levels decreased during exercise as compared with
the baseline values and that difference was found to be statistically significant
(p approximately 0.01). The above finding suggests opposite kinetics during
exercise of ET 1 between the two groups studied, which could explain effort
angina onset in patients with syndrome-X.
PMID- 9638964
TI - Simvastatin compared to fluvastatin in the reduction of serum lipids and
apolipoproteins in patients with ischaemic heart disease and moderate
hypercholesterolaemia.
AB - OBJECTIVE: Inhibitors of HMG-CoA reductase are widely used for the treatment of
hypercholesterolaemia and have recently been shown in the Scandinavian
Simvastatin Survival Study (4S), to reduce coronary mortality as well as total
mortality in CH D patients. Although a couple of studies have already established
the efficacy ratio between simvastatin and fluvastatin, one of the newest members
of this class, we considered it to be important to verify the comparative
efficacy in patients with coronary artery disease in the same type of patients
that were included in 4S particularly since the previous studies include rather
few patients with CHD, 17-28% only. METHODS AND RESULTS: Three Scandinavian lipid
clinics participated in this randomized double-blind study and enrolled a total
of 113 hypercholesterolaemic patients with a profile similar to the 4S patients,
i.e. either a history of typical angina pectoris lasting at least three months or
a myocardial infarction at least six months before the study and with moderate
hypercholesterolaemia, total serum cholesterol between 5.5 and 8.0 mmol/l. After
a diet run-in period lasting at least 8 weeks, followed by a two week placebo
period, patients received treatment with active drug for a 16 week period, with
measurement of lipids using the same technique and laboratory as was used in 4S.
Patients were randomly assigned to simvastatin 20 mg or fluvastatin 20 mg. If
after 6 weeks of double-blind treatment, the 4S total cholesterol target of < or
= 5.2 mmol/l total serum cholesterol had not been reached, the dose was doubled
at the next visit, i.e. at week 10 based upon blinded titration information from
the central lipid laboratory like in the 4S study. A final assessment of serum
lipids and lipoproteins was made at week 16. The mean percent reductions in LDL
cholesterol from baseline were 37% and 40% in the simvastatin group compared to
19% and 26% in the fluvastatin group, at weeks 10 and 16, respectively (p <
0.001). In the simvastatin group 18 percent of the patients needed an increase in
the dose to 40 mg compared to 63 percent in the fluvastatin group (p < 0.001). At
the 20 mg dosage, simvastatin produced a lowering of LDL-cholesterol
approximately twice that of fluvastatin 20 mg and resulted in 82% of patients
achieving the cholesterol target levels as defined in the 4S study, compared to
19% for fluvastatin. All other recorded lipid variables showed differences which
favoured simvastatin over fluvastatin at comparable doses including serum
triglyceride reductions where serum triglycerides at week 6 were borderline
significantly different between the two groups. Patient tolerability of the two
drugs was similar. CONCLUSION: At the recommended doses in patient with angina or
a prior MI and mild to moderate hypercholesterolaemia simvastatin is considerably
more effective than fluvastatin in lowering serum total cholesterol, LDL
cholesterol as well as other serum lipid risk factors. At an average titrated
dose of 32 mg less than 50% of the fluvastatin patients reached the 4S
cholesterol target of < 5.2 mmol/l compared to 89% of the simvastatin patients at
an average dose of 23 mg daily and only 13% of the fluvastatin patients achieved
an LDL-cholesterol reduction of at least 40% compared to 63% of the simvastatin
patients.
PMID- 9638965
TI - The use of low-molecular-weight heparins in cardiovascular disease.
AB - Unfractionated heparin (UFH) has been used for decades as an effective and
relatively inexpensive agent in the prevention of venous and arterial
thromboembolic events. Low-molecular-weight heparin (LMWH) preparations are
obtained by chemical or enzymatic depolymerization of unfractionated commercial
grade heparin; their mean molecular weights range from below 4,000 to about 6,500
D (Table 1). Their mechanism of antithrombotic action is basically similar to
that of UFH - binding to antithrombin to inhibit activated coagulation factors -
but they have a different relative potency (to some extent also inter
individually) of anti-Xa versus anti-IIa activity. Shorter fragments which
contain the essential pentasaccharide to bind to antithrombin but lack the
required chain length to bind at the same time to thrombin, only inhibit
activated Factor X. Fragments above 5,000 D which contain the pentasaccharide
maintain their property to inhibit Factor Xa but with increasing chain length,
they become stronger inhibitors of thrombin. LMWHs have little or no effect on
global tests of blood coagulation such as the activated partial thromboplastin
time when used in prophylactic or therapeutic dosages. A specific assay of anti
Xa activity is required to monitor biological activity but this is rarely needed.
The main advantage of LMWHs for clinical practice derive from their
pharmacokinetic properties. UFH binds to plasma proteins, endothelial cells and
platelets. This saturable mechanism clears heparin rapidly from the circulation
(the plasma half-life is non-linearly dose-related) and is held responsible for
the large variation from person to person and from moment to moment in biological
and clinical response. LMWHs bind far less to these elements and therefore have a
2 to 4-times longer plasma half-life, a markedly better bioavailability when
injected subcutaneously and a more stable dose response. They also have a lower
toxic effect in terms of heparin-induced thrombocytopenia which may be related to
their lesser interaction with platelets.
PMID- 9638966
TI - Sudden death in hypertrophic cardiomyopathy: risk stratification and prevention.
AB - Hypertrophic cardiomyopathy is an important cause of sudden death in young and
asymptomatic patients. Young athletes and patients with unexplained sudden death,
including their relatives, should be screened for its presence. Risk
stratification identifies a high-risk group, in which preventive measures should
be taken to reduce the risk for sudden death: moderate to heavy physical activity
has to be avoided and arrhythmias with haemodynamic impact should be rigorously
prevented.
PMID- 9638967
TI - Left atrial lipoma: case report and review of the literature.
PMID- 9638968
TI - Magnetic resonance imaging in a patient with a dual-chamber pacemaker.
AB - The presence of an implanted cardiac pacemaker has been considered an absolute
contraindication for magnetic resonance imaging due to the interactions between
the pulse generators and the magnetic and radiofrequency fields generated by the
magnetic resonance unit. We describe the case of a patient with a dual-chamber
pacemaker who underwent two magnetic resonance imaging examinations of the head
without any sequelae. Both procedures were performed with a 1 Tesla unit, with
the pacemaker programmed to the AOO mode. The only interference observed was
activation of the reed switch -probably due to the static magnetic field-
resulting in asynchronous atrial pacing at the magnet rate. Although the general
policy of never exposing a patient with a pacemaker to magnetic resonance imaging
should not be revised, we think that if the testing is considered essential, it
could be safely used in certain carefully selected patients.
PMID- 9638969
TI - Cardiac graft vasculopathy: aetiologic factors and therapeutic approaches.
AB - Heart transplantation has become an accepted and successful treatment for end
stage heart disease with survival rates of 80-90% after one year and 70% after 5
years. During the early posttransplant period (6-12 months), patients are subject
to two major complications: rejection and infection. Fortunately, a certain
degree of graft tolerance develops, allowing the immunosuppressive therapy to be
progressively tapered off with a concomitant decrease in infectious problems.
Long-term survival, however, is largely dependent on the development of an
accelerated atherosclerosis in the graft, which is believed to represent some
kind of chronic rejection. This transplant vasculopathy is documented by means of
coronary angiography with an incidence of approximately 5 to 10% per year. It is
not surprising therefore that major interest has risen concerning risk factors
promoting this pathology.
PMID- 9638970
TI - Non-fatal sustained ventricular fibrillation.
PMID- 9638971
TI - Structure and function of P-selectin glycoprotein ligand-1.
AB - Directed emigration of leukocytes into inflammatory sites and lymphatic tissues
is orchestrated by the regulated expression of adhesion and signaling molecules
on cells within the vasculature. The selectin family of adhesion molecules that
are expressed on activated endothelial cells (E-selectin and P-selectin),
activated platelets (P-selectin), and peripheral blood leukocytes (L-selectin),
mediate tethering and rolling of leukocytes to the vessel wall in the
microcirculation. Selectins promote these interactions by binding to
glycoconjugate ligands expressed on apposing cells. Selectin-mediated rolling is
a prerequisite for firm adhesion and subsequent transendothelial migration of
leukocytes into tissues. This review will focus on the structure and function of
P-selectin glycoprotein ligand-1 (PSGL-1, CD162). PSGL-1 is a disulfide-bonded
homodimeric mucin-like glycoprotein on leukocytes that interacts with P-, L-, and
E-selectin. PSGL-1 mediates leukocyte-endothelial and leukocyte-platelet adhesion
by binding to P-selectin expressed on activated endothelium and platelets and
PSGL-1 mediates leukocyte-leukocyte adhesion by binding to L-selectin expressed
on apposing leukocytes. PSGL-1 is unique in that it is the only selectin
glycoprotein ligand that has been directly demonstrated to mediate cell-cell
adhesion in vitro and in vivo.
PMID- 9638972
TI - Therapy-related chronic myeloid leukemia: an epidemiological, clinical and
pathogenetic appraisal.
AB - Second primary cancers represent an important complication of modern chemotherapy
and radiotherapy. Therapy-related (tr) leukemias are among the most common second
malignancies in both pediatric and adult populations. Whereas a reasonable amount
of data is available regarding the epidemiology, molecular pathogenesis, clinical
behavior and response to therapy of second primary acute leukemias, very little
is known about therapy-related chronic myeloid leukemia (tr-CML). A better
characterization of this entity could increase our understanding about the
mechanisms of carcinogenesis, specially the induction of specific genetic
abnormalities, e.g., BCR-ABL fusion, following chemotherapy and/or radiotherapy
exposure, could facilitate the investigation of the kinetics of the development
of CML, and also provide a model to study molecular events that might precede its
development. Review of 32 tr-CML cases suggests that there are no clinically
appreciable differences between tr-CML and de novo CML cases. Analysis of large
epidemiological studies that investigated the risk of second primary leukemias
has not shown any clear evidence of a higher risk of CML among individuals who
underwent treatment for a primary cancer over the general population. The cancer
predisposing syndromes, the detection of BCR-ABL transcripts in healthy
individuals, and the induction in vitro of BCR-ABL fusions by ionizing radiation,
are all discussed in the context of tr-CML. Finally, the need for a large
epidemiological study to specifically assess the risk of developing second
primary CML after chemotherapy and/or radiotherapy is stressed.
PMID- 9638973
TI - CDKN2 (MTS1/p16INK4A) gene alterations in adult T-cell leukemia/lymphoma.
AB - p16INK4A is a cyclin-dependent kinase inhibitor (CDKI), and regulates the cell
cycle negatively. Recently, p16INK4A protein was shown to be encoded by the CDKN2
gene, which is identical to multiple tumor suppressor gene 1 (MTS1) on chromosome
9p21, where genetic alterations occur frequently in many malignant tumors. As the
loss of p16INK4A function by genetic alterations leads to inappropriate
progression of the cell cycle, the CDKN2 gene has been investigated intensively
as a new candidate tumor suppressor gene in many malignant tumors. Adult T-cell
leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy associated with human
T-cell lymphotrophic virus type 1 (HTLV-1). As the development to ATL is believed
to require not only HTLV-1 infection but also accumulation of genetic
alterations, we investigated the relationship between alterations in the CDKN2
gene and ATL. Alterations in the CDKN2 gene were detected in approximately 15 to
20% of ATL patients. Interestingly, most of the patients with CDKN2 gene
alterations had the aggressive form of ATL. The CDKN2 gene appears to be the
major tumor suppressor gene on chromosome 9p21, and alteration in this gene may
play an important role during late stages in the transformation process induced
by HTLV-1.
PMID- 9638974
TI - CD73 and adhesion of B-cells to follicular dendritic cells.
AB - CD73, otherwise known as ecto-5'-nucleotidase, is a lymphocyte maturation marker
which is involved in intracellular signalling, lymphocyte proliferation and
activation. In addition, we have demonstrated that CD73 is involved in mediating
lymphocyte binding to in vitro cultured endothelial cells and in controlling
adhesion between freshly isolated germinal center B-cells and follicular
dendritic cells (FDC). In secondary lymphoid tissues, CD73 is expressed on FDC in
the light zone of the germinal center as well as on small, resting mantle zone B
cells but not on B-cells within germinal centers. In this review article, the
potential role of CD73 in controlling B-cell-FDC interactions and B-cell
maturation will be discussed.
PMID- 9638975
TI - Growth characteristics of myelodysplastic CD34+ cells.
AB - Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of
hematopoiesis entailing hyperproliferative and ineffective hematopoiesis
associated with morphologic evidence of marrow cell dysplasia resulting in
refractory cytopenia(s), and an increased risk of transformation into acute
myeloblastic leukemia (AML). The administration of colony-stimulating factor(s)
(CSFs) to patients with MDS increased blood neutrophil concentrations, in most
patients, and it was anticipated to be of benefit to prevent infections. The
progression to AML while being treated with CSFs has come under close scrutiny.
In vitro studies are expected to produce more pertinent criteria for selection of
patients who are likely to benefit, as well as the overall benefits of various
therapies. For this purpose, in vitro colony assays are an excellent approach for
investigation of the biologic characteristics of MDS progenitor cells. The stem
cell phenotype CD34 is the one of the best markers of progenitor cells, and can
be used for the purification of these cells to unify levels of maturation; a
direct comparison of proliferative and differentiative capacity of MDS progenitor
cells with normal CD34+ cells can thus be made. The properties of MDS CD34+ cells
are described here in association with proliferation and differentiation, with
special emphasis on the role of stem cell factor (a ligand for c-kit) in leukemic
type growth of MDS CD34+ cells.
PMID- 9638976
TI - Regulation of myeloid and lymphoid development of hematopoietic stem cells by
bone marrow stromal cells.
AB - Development of hematopoietic stem cells is regulated by stromal cells of the bone
marrow. Many stromal cell lines have been established from temperature-sensitive
SV40 large T-antigen gene transgenic mice and used to examine regulation of the
purified stem cells. When the sorted stem cells were cocultured on the stromal
cell layers, cobblestone formation was induced by the stromal cells. The
cobblestones were formed by finite cell division (8 divisions on average) of
sorted Lin- c-Kit+ Sca1+ stem cells committed to myeloid or lymphoid lineages.
These stromal cell lines showed variable activities supporting the stem cell
development. In one stromal cell line, TBR59, two waves of cobblestone formation
committed to either myeloid lineage or lymphoid lineage were induced. TBR31-1,
another bone marrow stromal cell line, induced only the cobblestone formation
committed to lymphoid lineage. These results indicate that the bone marrow
stromal cells selectively induce lineage-specific commitment of the stem cells.
Both cobblestone formations require c-Kit function as well as adhesive
interaction through VLA4 and VCAM1.
PMID- 9638977
TI - Production and effects of interleukin-6 and other cytokines in patients with non
Hodgkin's lymphoma.
AB - Cytokines are regulatory molecules that are produced by a variety of cell types
and are characterized by numerous biologic functions involved in the regulation
of the immune system and hematopoiesis. This review summarizes the functions and
regulation of cytokines in lymphomas and discusses the effect of a specific
cytokine, interleukin-6 (IL-6), in B-cell lymphomas. IL-6 is a multipotent
cytokine that can mediate the differentiation of B-cells into immunoglobulin
secreting cells, stimulate the autocrine or paracrine growth of myeloma cells,
induce acute-phase proteins in liver cells, and may influence the pathogenesis of
several diseases by autocrine or paracrine mechanisms. Patients with non
Hodgkin's lymphoma (NHL) have increased serum concentrations of IL-6; increased
IL-6 levels can be associated with the presence of B-symptoms. Data presented in
this review indicate that neoplastic cells from patients with NHL contained high
concentrations of IL-6. Thus, elevated serum levels of IL-6 appear to originate
from the lymphoma cells in patients with B-cell NHL, suggesting that the
neoplastic cells may modulate the general status of patients with B-cell NHL. The
inhibition or modification of the production of IL-6 in lymphoma cells may lead
to a more effective control of the general status of patients with B-cell NHL.
PMID- 9638978
TI - The tumor necrosis factor signaling complex: choosing a path toward cell death or
cell proliferation.
AB - Signal transduction pathways which are initiated by the tumor necrosis factor
(TNF) utilize receptors which are devoid of intrinsic catalytic activity.
Recently identified two families of proteins that directly associate with the
cytoplasmic domains of the TNF receptor family members, have partially bridged a
molecular gap within the TNF-induced signaling pathways. Clearly, there are
numerous alternate routes that originate from the TNF ligand-receptor assembly
and terminate on the diverse cellular responses, including proliferation,
differentiation, or death. This review focuses on recent advances characterizing
the TNF ligand-receptor signaling network, which allow to better understand its
participation in a life-death balance within the target cell.
PMID- 9638979
TI - Analysis of the t(2;5) (p23;q35) translocation in CD30+ primary cutaneous
lymphoproliferative disorders and Hodgkin's disease.
AB - The t(2;5) (p23;q35) chromosomal translocation is found in about 40% of lymph
node-based CD30+ anaplastic large cell lymphomas of T-cell or null-cell lineage.
This translocation results in the expression of a fusion protein containing the
catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the
promoter for nucleophosmin (NPM), a nucleolar phosphoprotein. Expression of ALK
activity, normally absent in lymphocytes, is postulated to be involved in the
pathogenesis of lymphomas bearing the t(2;5) translocation. Certain primary
cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to
contain CD30+ large lymphoid cells. In order to determine the role of the t(2;5)
translocation in these diseases, several investigators have employed a variety of
techniques including cytogenetics, genomic Southern blot analysis, RNA- and DNA
based PCR assays, various forms of in-situ hybridization, and immunostaining for
the p80 fusion protein encoded by the chimeric t(2;5) transcripts. These studies
included approximately 415 cases of Hodgkin's disease, 65 cases of CD30+ primary
cutaneous large cell lymphoma, and 38 cases of lymphomatoid papulosis. The
aggregate results of these studies indicate that the t(2;5) translocation or
other somatic mutations resulting in inappropriate expression of ALK are involved
rarely if at all in the pathogenesis of Hodgkin's disease, but may be present in
about 10% of cases of lymphomatoid papulosis and 20% of cases of CD30+ primary
cutaneous large cell lymphoma. However, the t(2;5) has not been detected yet in
any case involving multiple or secondary CD30+ lymphoproliferative disorders,
thereby providing no evidence for a role in tumor clone progression. Additional
studies will be needed to determine if t(2;5) status has any clinical
significance for patients with CD30+ primary cutaneous lymphoproliferative
disorders.
PMID- 9638981
TI - Enhanced proliferative activity of PIXY-321, the granulocyte-macrophage colony
stimulating factor and interleukin-3 fusion protein.
AB - Previous studies with the granulocyte-macrophage colony-stimulating factor (GM
CSF) and interleukin-3 (IL-3) fusion protein, PIXY-321, demonstrated the enhanced
biological activity of this molecule in comparison with GM-CSF or IL-3 alone or
in combination. Here, we performed experiments to determine the proliferative
effect of PIXY-321 on 13 constitutively growth factor-dependent human leukemia
cell lines in comparison with GM-CSF, IL-3 and their combination using as read
out parameters the 48-hour 3H-thymidine incorporation assay and viable cell
counts after in vitro culture for 7-8 days. Whereas one cell line was not
responsive to any of these three cytokines, the other 12 cell lines showed
variable degrees of growth in response to these effector molecules. PIXY-321
increased proliferation as measured by thymidine uptake relative to IL-3, GM-CSF
or GM-CSF + IL-3 by 34% (range 5-448%), 12% (range 0-122%), and 6% (range 1-13%),
respectively. PIXY-321 induced a mean increase of 32%, 30% and 11% in cell counts
relative to the values obtained with IL-3, GM-CSF or GM-CSF + IL-3, respectively.
Altogether, these data indicate that PIXY-321 stimulates proliferation of
immature hematopoietic cells substantially better than equivalent concentrations
of the single growth factors GM-CSF and IL-3. This hybrid growth factor showed a
marginal to modest, but definite and reproducible increase in proliferation
compared to the combination of GM-CSF plus IL-3. In summary, the fusion cytokine
protein PIXY-321 appears to have biological effects superior to those elicited by
its components, singly or in combination. This unique molecule should represent a
useful tool in studies on the mechanisms underlying cytokine ligand-receptor
interaction and the subsequent signal transduction. The use of PIXY-321 provides
an opportunity for taking greater advantage in vitro and in vivo of the
hematopoietic stimulatory activities of GM-CSF and IL-3.
PMID- 9638980
TI - HIV-related non-Hodgkin's lymphoma: CHOP induction therapy and interferon-alpha
2b/zidovudine maintenance therapy.
AB - In a prospective multicenter study 68 out of 158 patients with HIV infection and
malignant lymphoma were assigned to a risk-adapted induction therapy using the
following algorithm: High-risk patients fulfilled 2 of 3 criteria: T4 lymphocytes
<50/microL; WHO activity index 3 or 4; pre-existing AIDS-defining opportunistic
infection. Normal-risk patients received 4 to 6 cycles of CHOP chemotherapy;
those that achieved complete remission (CR) received zidovudine (500 mg/d) and
interferon-alpha maintenance therapy (5 million units three times a week) for one
year. High-risk patients received low-dose CHOP or vincristine/prednisone
chemotherapy. Supportive care was performed with pentamidine inhalation and G
CSF. Intrathecal (it) methotrexate was given for CNS prophylaxis. The median
survival was 634 days for 38 patients of the normal-risk group and 129 days for
30 patients of the high-risk group. 18 high-risk patients treated with low-dose
CHOP had better survival (156 days) than 12 patients treated with
vincristine/prednisone (72 days p=0.044). 68% of the patients in the normal-risk
group achieved complete remission. 5 out of 18 high-risk patients treated with
low-dose CHOP achieved complete remission. Three normal-risk patients developed
fatal opportunistic infections during chemotherapy. Immune parameters
deteriorated after CHOP induction and partially recovered with maintenance
treatment. We conclude that the normal-risk patients survived longer than
reported in most published studies. Toxicity was low. Low-dose CHOP seems to be
superior to vincristine/prednisone therapy in high-risk patients.
PMID- 9638982
TI - Gastrointestinal emergencies in patients with acute intestinal graft-versus-host
disease.
AB - Acute intestinal graft-versus-host disease (GVHD) develops in about 30-50% of
allogeneic bone-marrow transplant recipients: 10-20% have gastrointestinal
emergencies (hemorrhage or perforation). Mortality reaches 30-60% in patients
with acute, grade 2-4 GVHD. We studied 36 bone marrow recipients in whom acute
intestinal GVHD developed. Seven had gastrointestinal emergencies: 4 severe
gastrointestinal bleeding and 3 acute peritonitis. Three patients with
gastrointestinal bleeding and one patient with peritonitis responded to medical
therapy. Three needed surgery: one with bleeding and two with peritonitis, while
1 patient had embolization. Of the 7, two patients died, one after embolization
and one after surgery. Two of the three surgically-treated cases are still alive
several years after operation. From this experience we feel that surgery for
gastrointestinal bleeding in acute GVHD is indicated only when medical treatment
fails. Severe neutropenia, thrombocytopenia (<10.000 x mm3) and blood cultures
positive for CMV have an unfavorable prognostic value.
PMID- 9638983
TI - Expression of p53 predicts treatment failure in aggressive non-Hodgkin's
lymphomas.
AB - Approximately 50% of patients with aggressive non-Hodgkin's lymphomas (NHL)
achieve a complete remission (CR) and cure with combination chemotherapy. The
International Index is a useful clinical measure that predicts the patients'
tolerance of therapy and likelihood of achieving CR, but it is not a direct
measure of chemosensitivity. In this study we have investigated the predictive
value of the tumor suppressor gene, p53, as a biological marker for response to
treatment in the aggressive NHL. A retrospective study was carried out on 50
patients with aggressive NHL who were treated with CHOP chemotherapy. Treatment
outcome was correlated with the expression of p53 in the lymphoma, as measured by
routine immunohistochemistry using the monoclonal antibody Do-7. Forty percent of
the lymphomas had >5% of the cells staining positively for p53 and this finding
correlated significantly with response to treatment. Fifty percent of patients
with p53 positive tumors achieved a CR versus 77% of patients with p53 negative
tumors. In addition, the relapse rate and time to relapse were significantly
different in the two groups. In the p53 positive group, 60% of patients relapsed
in a median time of 6 months, whereas 26% of the p53 negative group relapsed with
the time to relapse being >22 months. The overall survival of the p53 positive
group (17 months) was significantly shorter than that of p53 negative group (>24
months). These results suggest that the immunohistochemical assessment of p53 is
a simple and important prognostic measure for patients with aggressive NHL who
are treated with CHOP chemotherapy.
PMID- 9638984
TI - Myeloperoxidase gene expression in infant leukemia: a Pediatric Oncology Group
Study.
AB - A high incidence of co-expression of myeloid-associated antigens in infant B
precursor Acute Lymphocytic Leukemia (B-ALL) has been reported, but the
significance of this finding is uncertain. To further assess myeloid
differentiation and its prognostic significance in this disease, we investigated
the frequency of myeloperoxidase (MPO) gene expression in the blast cells from 43
infants with B-ALL registered in a Pediatric Oncology Group (POG) Pilot Study for
Treatment of Infant ALL, utilizing a molecular probe for detection of MPO
messenger RNA (mRNA) by Northern blot hybridization and a monoclonal antibody to
detect MPO-protein by immunohistochemical staining. Sufficient RNA for Northern
blot was extracted from 32 bone marrow or blood samples. In two cases, MPO mRNA
was determined by a reverse transcriptase-polymerase chain reaction assay and was
negative in both cases. MPO-specific transcripts (MPO+) were present in 19 of 34
(56%) samples analyzed. Immunoreactive MPO protein was positive in 13 of the 20
(65%) patients studied. No correlation was found between MPO gene expression and
clinical or laboratory features, karyotypic patterns or clinical outcome. The
high frequency of MPO gene expression demonstrated in this study suggests that
leukemogenic events in many cases of infant B-ALL appear to involve a pluripotent
stem cell not yet fully committed to lymphoid differentiation.
PMID- 9638985
TI - Residual leukemic cell counts in the bone marrow at the end point of intensive
induction therapy may be a prognostic factor for acute myeloblastic leukemia in
adults.
AB - Between January 1990 and May 1994, 59 previously untreated adult patients with
acute myeloblastic leukemia (AML) were treated with a combination of behenoyl
cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and
prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR).
The Kaplan-Meier analysis revealed an actuarial probability for remaining in
remission of 36% in patients who achieved remission and a survival of 29% in all
patients at 5 years. A favorable factor relative to achieving CR was performance
status (P=0.04). In addition the presence of 300 cells/microl or less of residual
leukemic cell counts in the bone marrow at the end point of induction therapy
tended to favor remission (P=0.06) using the multivariate analysis with a
multiple logistic regression model. In addition the residual leukemic cells
counts of less than 300/microl in the bone marrow at the end point of induction
therapy was the most significant factor for durable remission (P=0.05) by the
Cox's proportional hazard model. We concluded that residual leukemic cells counts
in the bone marrow at the end point of intensive induction therapy is a valuable
prognostic factor for adults receiving response-oriented individualized induction
therapy for AML.
PMID- 9638986
TI - High incidence of chemotherapy-induced acral erythema in female patients with non
Hodgkin's lymphoma treated with the VACOP-B regimen.
AB - Seven patients, all females out of 29 with non-Hodgkin's lymphoma (NHL) (16 males
and 13 females) treated with the VACOP-B regimen utilizing granulocyte-colony
stimulating factor (G-CSF) support developed chemotherapy-induced acral erythema
(CAE). In contrast, none of 32 patients with NHL who were treated with CHOP,
MACOP-B, or biweekly CHOP regimens without G-CSF developed CAE. Total dose
intensities of VACOP-B regimen were higher than those of the three other
regimens. However, no significant difference in dose intensities of each drug in
the patients treated with the VACOP-B regimen was found between male and female
patients and between female patients with or without CAE. The cause of the high
incidence of CAE (7/13) in the female patients treated with VACOP-B regimen
remains unknown. However, female sex hormones may increase susceptibility to CAE.
Since the occurrence of CAE interrupts intensive chemotherapy and reduces the
cure rate, high risk patients for CAE should be carefully monitored for early
symptoms and signs of CAE and should be treated early and appropriately.
PMID- 9638987
TI - Detection of B-cell monoclonality in fine needle aspiration by PCR analysis.
AB - Cytologic examination of fine-needle aspiration (FNA) sometimes fails to diagnose
the malignant nature of B-cell proliferations. In this study we analyzed the Ig
gene rearrangement of 49 FNA samples by polymerase chain reaction (PCR) in order
to evaluate whether molecular analyses can improve the accuracy of FNA. Twenty
six patients had non-Hodgkin's lymphoma, 11 had reactive lymphoid diseases, 5 had
chronic inflammation and 7 had carcinoma. A semi-nested PCR was performed using
an oligoprimer specific for consensus sequences of the V regions (FR3A) and two
oligoprimers derived from conserved sequences of the J regions (LJH and VLJH).
Histologic examination always followed the molecular and cytologic analysis. The
sensitivity of PCR and FNA morphological examination in detecting a neoplastic
pattern was 92% and 78%, respectively. When samples were considered inadequate
for cytologic examination, PCR always reached a diagnosis consistent with the
histologic features. Our results demonstrate that PCR analysis of FNA specimens
is a reliable and sensitive method capable of enhancing the diagnostic accuracy
of cytologic examination.
PMID- 9638988
TI - All trans retinoic acid with low dose cytosine arabinoside in the treatment of
myelodysplastic syndrome.
AB - The demonstration of synergistic interaction between differentiation inducing
agents and DNA synthesis inhibitors suggests that these two groups act by two
different mechanisms. We prospectively studied the response rate, response
duration, survival, and toxicity in 10 patients with myelodysplastic syndrome
(MDS) treated with all trans retinoic acid (ATRA) and low dose cytosine
arabinoside (ara-C). These patients diagnosed between October 1993 and May 1995
were treated with ATRA (45 mg/M2/day) for 90 days followed by 90 mg/M2 on
alternate day till Day 275; together with Ara-C (10 mg/m2) subcutaneously twice
daily for 21 days for a total of 6 cycles. These patients were analyzed for
response after 3 cycles of LD Ara-C and at the time of completion of therapy.
Toxicity was recorded at the end of each cycle of Ara-C. There were 6 male and 4
female patients in the age range of 24 to 76 years. The morphological diagnosis
was chronic myelomonocytic leukemia in 2, refractory anemia with excess blasts in
4 and refractory anemia with excess blasts in transformation in 4. Only 1 patient
achieved a complete remission and 1 patient achieved a partial response. Four
patients had progressive disease on treatment. One patient died of neutropenic
sepsis and 1 of resistant thrombocytopenia and intracranial hemorrhage while on
treatment. One patient refused further treatment after a minor clinical response
and in 1 patient treatment was stopped due to toxicity. This data in a pilot
study with a limited number of patient suggests that ATRA in combination with Ara
C has little effect in MDS.
PMID- 9638989
TI - Familial hairy cell leukemia.
AB - Familial hairy cell leukemia (HCL) occurs rarely, and HCL occurring in
association with other hematologic malignancies is even rarer. We describe two
cases of familial HCL syndromes: a mother and son with HCL, and a HCL patient
whose aunt developed Hodgkin's Disease (HD). This is the first reported familial
association of HCL with HD.
PMID- 9638990
TI - Mediastinal large-cell lymphoma with sclerosis refractory to conventional
chemotherapy can respond after daily oral cyclophosphamide.
AB - Mediastinal large-cell lymphoma with sclerosis (MLCLS) is a distinctive subtype
of non-Hodgkin's lymphoma (NHL) with unique clinicopathology aspects and
aggressive behavior. Prompt diagnosis and aggressive chemotherapy followed by
consolidation radiotherapy may result in long-term survival in the majority of
cases. However, a subset of patients do not respond to first-line or salvage
treatment and have a poor prognosis. We report here a 27-year-old man with MLCLS
resistant to several conventional chemotherapies and to radiotherapy who achieved
a very good partial remission after one year's treatment with daily oral
cyclophosphamide (100 mg/day). This is the first report of refractory MLCLS with
good response to daily oral cyclophosphamide. This case suggests that daily oral
monochemotherapy might be beneficial for some patients with mediastinal large
cell lymphoma with sclerosis refractory to conventional intravenous
chemotherapies and radiotherapy.
PMID- 9638991
TI - Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity
and acute renal failure.
AB - We describe the case of a 35-year old male who developed acute renal failure
following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma.
Serum methotrexate levels reached 37 micromol/l, and remained higher than 1
micromol/l for more than a week. Folinic acid rescue was intensified to 200-400
mg intravenously every 4 hours. As methotrexate binds markedly to proteins,
plasma exchange was initially chosen, 4 sessions being performed from day 2 to
day 4. The methotrexate pharmacokinetic profile was not significantly modified
during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno
venous hemodiafiltration was therefore performed from day 5 to day 10. This
procedure also seemed ineffective, with evidence of low ultrafiltrate clearance.
No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal
procedures appear to have a limited role in the setting of overexposure to
methotrexate. The use of very high doses of folinic acid in our case probably
played a major role in the eventual favorable outcome.
PMID- 9638992
TI - Teaching cases from the Royal Marsden Hospital. Case 16: T-cell non Hodgkin's
lymphoma associated with hypercalcaemia in a black Caribbean.
PMID- 9638993
TI - Nd Yag laser angioplasty: a safe procedure in peripheral vascular surgery.
AB - BACKGROUND: Thirty-three patients (34 limbs) with peripheral vascular occlusive
disease were treated with Nd Yag laser assisted angioplasty over a three-year
period (1989-1991). METHODS: Sixteen males and 17 females were included in the
study. The mean age of all patients was 70.29 (44-86) years. Twenty-two (66.7%)
patients were smokers, 21 (63.6%) had coronary artery disease and 14 (42.4%) had
diabetes mellitus. Thirty-three patients (100%) had disabling intermittent
claudication, 20 patients (60.6%) had rest pain, 2 patients (6.1%) had ulcers and
10 patients (30.3%) had gangrenous changes. Thirty-nine vessels were treated; 34
(87.2%) superficial femoral arteries, 4 (10.3%) popliteal arteries and 1 external
iliac artery. Eleven (28.2%) vessels were totally occluded and the remaining 28
(71.8%) vessels had high grade stenosis of more than 90%. The mean preoperative
ABI Index was 0.23+/-12. RESULTS: The preoperative angiogram showed poor out-flow
in 24 (70.6%) extremities, 1 patent distal vessel in 7 extremities (20.6%) and at
least 2 vessels in 3 extremities (8.8%). The patients were followed up for a
period of 9.9 months (20 days-30 months). The procedure could not be done in 2
extremities. All the remaining 32 extremities had patent vessels at the end of
the procedure. Fifteen (48.4%) patients stated that they improved but remained
symptomatic. Twelve (38.7%) were completely asymptomatic, 3 (9.7%) patients had
no change in their symptoms and 2 patients worsened at the end of the follow-up
period. The mean postoperative ABI was 0.78. Bleeding from the puncture site
requiring closure was the most common complication of the procedure in 6 patients
(19.4%). Angioplasty in 5 of these patients was done by the open technique. Other
complications included hematoma in 3 (9.7%) patients and one case (3%) of artery
perforation. Among those who remained asymptomatic at the end of the follow-up
period the mean change in ABI was 0.625+/-0.19, those who improved but remained
symptomatic the mean ABI change was 0.43+/-0.25 while those whose symptoms did
not change or worsened the mean ABI change was 0.12+/-0.13. The ABI change in the
first two groups was significantly higher than the last one (p<0.006 and p<0.001
respectively). There was no significant difference in the outcome of LABA between
stenosed and occluded vessels. Smoking was significantly higher in the
symptomatic patients (7/20) compared to those who were asymptomatic 5/12, p<0.02.
Diabetes mellitus, cardiovascular disease and the preoperative ABI were not
significant variables in the outcome of angioplasty. CONCLUSIONS: In conclusion,
Nd Yag laser assisted angioplasty is a safe procedure. It could relieve symptoms
in 87.1% of cases. Change in the ABI and smoking are predictive of the success of
the procedure.
PMID- 9638994
TI - Occlusive disease associated with popliteal aneurysms: impact on long term graft
patency.
AB - OBJECTIVE: Correlate graft patency and limb salvage outcomes following popliteal
aneurysm repair with the extent of tibial occlusive disease. EXPERIMENTAL DESIGN:
Retrospective study with a mean follow-up of 36 months (range, 2-96 months).
SETTING: Institutional teaching hospital. PATIENTS: Of 20 popliteal aneurysms
among 16 patients undergoing repair, 75% were associated with preoperative tibial
vessel occlusion. Normal, three vessel infrapopliteal runoff was present in 5
patients, two vessels in 7 patients, and one or no vessels in 8 patients. Fifty
percent of limbs were asymptomatic, while the remainder suffered from a variety
of ischemic symptoms. INTERVENTIONS: Eighteen of the 20 aneurysms were repaired
with femoropopliteal bypass grafts, and two femoral-tibial bypasses were
performed. Autogenous saphenous vein was used in 18 cases (10 in situ, 8
reversed) and PTFE in two short segment femoral-popliteal bypasses. MEASURES:
Graft patency was determined by presence of a palpable pulse, the re
establishment of normal ankle-brachial indices, or duplex scanning. Patency and
limb salvage rates were estimated using life table analysis by the Kaplan-Meier
method. RESULTS: Preoperative symptoms did not correlate with tibial runoff,
except in two patients presenting with acute thrombosis and ischemia. Cumulative
graft patency by life table analysis was not different for either good (2-3
vessels, N-12) or poor (0-1 vessels, N-8) runoff. Overall primary patency at 60
months was 73%, and cumulative secondary patency was 100% with no limbs lost at
60 months. CONCLUSIONS: Concomitant distal arterial occlusive disease is
frequently associated with popliteal aneurysms, yet did not appear to
substantially impact either long-term graft patency or limb salvage.
PMID- 9638995
TI - Abdominal aortic aneurysm and lower-limb occlusive arterial disease.
AB - BACKGROUND: Abdominal aortic aneurysms (AAA) are associated with lower-limb
occlusive arterial disease (LLOAD) in 20-40% of patients. Retrospective analysis
of 200 elective AAA repairs and comparison with literature data revealed that
LLOAD has little influence on standard therapeutic management of AAA. METHODS: In
this study, only 2.5% of the patients required femoropopliteal bypass along with
aneurysm repair. In contrast, aneurysm repair was associated with lumbar
sympathectomy in 30% of cases owing to existence of peripheral arterial disease.
RESULTS: Concurrent LLOAD did not significantly increase the operative mortality
of AAA, but postoperative peripheral arterial complications were more frequent in
patients with both aneurysmal and occlusive disease. CONCLUSIONS: Although
concomitant LLOAD did not adversely affect the long-term survival of patients who
underwent surgical repair of AAA, this subgroup of patients was at higher risk of
aggravation of their lower extremity arterial lesions.
PMID- 9638996
TI - Surgical experiences with peripheral arterial aneurysms due to vasculo-Behcet's
disease.
AB - BACKGROUND: Vascular involvement of Behcet's disease is currently considered as
an important sign of the clinical evolution of patients with Behcet's disease. In
addition, Behcet's disease is important in that it causes peripheral arterial
aneurysms. METHODS: In this report, 4 patients with vasculo-Behcet's peripheral
arterial aneurysms are presented. These aneurysms were distributed in the carotid
artery (n=1), popliteal artery (n=1) and femoral arteries (n=3). Operative
procedures included patch closure of a perforated wall for the carotid aneurysm,
arterial reconstruction with the autogenous saphenous vein for the femoral and
popliteal aneurysms. RESULTS: All four patients tolerated the operation well,
however, two of four patients required re-operation due to anastomotic
insufficiency later. CONCLUSIONS: Aneurysms associated with Behcet's disease have
a sudden onset in many cases and often result in rupture. Appropriate operative
procedures, including an adequate choice of anastomotic sites and reinforcement
of the suture, may reduce the incidence of complications in patients with
arterial aneurysms due to Behcet's disease.
PMID- 9638997
TI - Saphenous vein sparing surgery: principles, techniques and results.
AB - OBJECTIVE: Evaluation of saphenous vein sparing surgical procedures alternative
to high ligation and distal stab avulsion, in terms of effectiveness and
suitability for eventual bypass surgery. EXPERIMENTAL DESIGN: Prospective
evaluation of 421 operations for primary varicose veins, 64 external valve
plasties of the sapheno-femoral junction (EV-SFJ), (42 performed using the hand
sewing technique and 22 using the Veno-cuff device), mean follow-up 52 months,
and 357 hemodynamic correction of varicose veins (French acronymis CHIVA), mean
follow-up 49 months. Moreover, a subgroup of 27 patients was operated on using
the CHIVA technique in two steps, mean follow-up 18 months. SETTING: Institute of
General Surgery, University of Ferrara. Institutional practice, one-day surgery.
PATIENTS: Patients were selected using clinical and duplex scanning evaluations,
and classified according to CEAP criteria. Patients with varicose veins due to
sapheno-femoral reflux with duplex scanning evidence of mobile valve leaflets
underwent EV-SFJ. The other patients were operated on using the hemodynamic
correction technique. INTERVENTIONS: EV-SFJ restores valve function correcting
vein wall dilatation by applying an external prosthesis. CHIVA consists of
selected ligatures of the superficial veins that allow superficial blood
aspiration in the deep veins through the perforators as well as the preservation
of saphenous drainage. MEASURES: The outcome was evaluated with independent
clinical and ultrasonographic examinations; pre and postoperative AVP and LRR-RT
measurements were assessed in 125 cases. Data from self-assessment of the
functional and cosmetic result of the patients of the CHIVA group were also
obtained using a scoring system. Moreover, scanning the preserved long saphenous
vein the rate of long saphenous vein suitable as arterial conduit following
sparing surgery was also evaluated. RESULTS: Overall long saphenous vein patency
registered after EV-SFJ and CHIVA was 94%. Varicose veins recurrence rate was 12%
and 11%, respectively. Postoperative AVP and LRR-RT improvement was statistically
significant (p<0.001). CONCLUSIONS: These two alternative procedures seem to be
effective in varices treatment following the proposed indications and techniques.
In addition, they appear able to preserve a more significant rate of saphenous
veins suitable for eventual bypass surgery than high ligation and multiple
cosmetic avulsion.
PMID- 9638998
TI - Carotid string sign resulting from an aberrant branch of the internal carotid
artery.
AB - Branches of the extracranial internal carotid artery are very rare. A case is
reported wherein an aberrant artery originated from the bulb of the internal
carotid artery (ICA) approximately 2 cm from the bifurcation. The ICA was
occluded distal to the branch's origin. Arteriography in this case gave the
appearance of a carotid "string sign". Vascular surgeons and radiologists should
be aware of this anomaly when interpreting carotid arteriograms.
PMID- 9638999
TI - Traumatic pseudoaneurysm of the axillary artery following anterior dislocation of
the shoulder. Case report.
AB - Vascular complications are rare in cases of simple anterior dislocation of the
shoulder but the axillary artery or its branches may be damaged. Very few cases
are found in the literature reporting false aneurysms of axillary artery
secondary to blunt trauma to the shoulder. A case of pseudoaneurysm of the
axillary artery in a 75-year-old woman is reported. Diagnosis was suspected
because large pectoral haematoma with haemodynamic instability appeared a few
hours later after manual reduction of the dislocation. The pseudoaneurysm was
confirmed with selective angiography of the axillary artery. Arteriography should
be performed whenever vascular injury is suspected. Delayed recognition of these
lesions may lead to permanent neurologic deficits despite adequate vascular
repair of the axillary artery. A coordinated vascular and orthopaedic approach
and prompt surgical treatment may assure full upper limb function. Although
endovascular treatment of these lesions could seem attractive, we prefer to use
open surgical techniques because they allow us to treat frequent concomitant
injuries and perform decompression of the axillar fossa because of the large
haematoma.
PMID- 9639000
TI - Osteomyelitis of the fibula due to septic embolism: a rare complication of a
graft enteric erosion. Case report.
AB - We report the case of a 70-year-old female who experienced a graft enteric
erosion (GEE) three years after a right aorto-femoral bypass. She was treated by
right axillo-femoral bypass, removal of the aortic prosthesis and direct aortic
suture. The duodenum was stitched up and separated from the aorta by
omentoplasty. Bacteriological culture of the removed graft identified Escherichia
coli and Peptostreptococcus. Antibiotic therapy consisting of Amoxicillin and
Gentamycin was given for seven days. A month later this patient developed a
fibula osteomyelitis due to the same germs. She was then treated by surgical
excision of the infected tissues and by antibiotics: Amoxicillin, Metronidazole
and Gentamycin for one month. This case of embolism into bone due to GEE is a
rare complication which indisputably establishes a link between the spontaneously
septic cavity of the bowel and bone tissue by way of blood via the interstices of
the fabric. The prosthesis may be responsible for blood seeding infection and not
only a mere victim. The prosthesis acts as a porous membrane which allows two
opposite flows: the passage of blood from graft to bowel and germ migration from
naturally septic bowel to blood. When a GEE is encountered, a rigorous management
is required to prevent septic embolism. The precise timing of each step of the
surgical procedure remains difficult to codify.
PMID- 9639001
TI - Multivarious clinical manifestations of multiple pseudoaneurysms in Behcet's
disease.
AB - In Behcet's disease, an aneurysm is prone to progress rapidly to a
pseudoaneurysm. Acute limb ischemia due to acute thrombosis of a femoral
pseudoaneurysm and subsequent Horner's syndrome due to another subclavian
pseudoaneurysm are very rare but acceptable complications in Behcet's disease. We
present a case of Behcet's disease with multiple pseudoaneurysms, which also
showed these other clinical manifestations. Over a short time span, the patient
rapidly developed left femoral and right subclavian pseudoaneurysms, which were
successfully resected with graft replacements.
PMID- 9639002
TI - Dilatation of sealed Dacron vascular prostheses: a comparison of Gelseal and
Hemashield.
AB - OBJECTIVE: Early postoperative dilation of a gelatin-impregnated knitted dacron
prosthesis (Gelseal, Vascutek) and a collagen-impregnated woven Dacron prosthesis
(Hemashield, Meadox Medicals) was studied. EXPERIMENTAL DESIGN: Prospective
study. SETTING: Institutional clinical research. MATERIALS AND METHODS: A total
of 30 patients who underwent aortic repair for abdominal aortic aneurysm with a
Gelseal (n=15) or Hemashield (n=15) were studied. Prior to and immediately
following implantation, the diameter of each graft was measured with slide
calipers. The external diameter was examined by CT scan 4 weeks after surgery.
Early dilation of Gelseal and Hemashield was estimated and compared. RESULTS:
Prior to implantation, the external diameter of the Gelseal and Hemashield was
120% and 113% of the package size (PS), respectively, while the internal diameter
was 103% and 102% of the PS, respectively. Following implantation, the external
diameter of the Gelseal and Hemashield was 122% and 113% (immediately after) and
129% and 118% (4 weeks later) of the PS, respectively. CONCLUSIONS: The actual
dilation rate for the first 4 weeks after implantation was estimated as 8% with
the Gelseal and 4% with the Hemashield.
PMID- 9639003
TI - The effect of cardiopulmonary bypass on blood cell filterability in children
undergoing cardiac surgery.
AB - BACKGROUND: The extended use of cardiopulmonary bypass (CPB) in cardiac surgery
is limited because of damage to blood which in adults has been assessed by
alterations in blood cell rheology. Blood trauma assessment in children is
difficult because of the restrictions in sample volume and frequency but needs to
be established from time to time in order to study the tolerance to new surgical
and extracorporeal techniques. MATERIALS AND METHODS: Fourteen pediatric patients
undergoing cardiac surgery with CPB for congenital heart disease corrections were
studied. Whole blood, red blood cell and white blood cell rheology
(filterability) were monitored before, during and after CPB using the St. George
filtrometer that used small amounts of blood. RESULTS: The results showed that
all the rheologic parameters were altered during the blood trauma of CPB and were
outside the reference values before, during and after CPB. CONCLUSIONS: This
suggested that blood cell rheologic disturbances did not recover soon after CPB
and this may be of interest in long term follow-up to understand responses and
recovery patterns to disease and interventions associated with pediatric heart
surgery using CPB.
PMID- 9639004
TI - Papaverine solutions cause loss of viability of endothelial cells.
AB - OBJECTIVE: The optimal composition of the solution used for irrigation of
saphenous veins used for cardiac surgery may influence ultimate graft patency due
to potential injurious effects on the vein endothelium of some of the solution
constituents. EXPERIMENTAL DESIGN: The viability of cultured saphenous vein
endothelial cells was assessed after incubation of saphenous vein endothelial
cells with solutions containing saline, saline with papaverine (0.15 M NaCl, 32.5
mg/mL papaverine), culture medium and buffered saline solution (Plasma-Lyte-A).
RESULTS: Cell viability was significantly decreased after one hour incubation
with solutions containing saline with papaverine (24.4+/-9.4%) as compared to
culture medium and buffered saline solutions (medium 100%, Plasma-Lyte-A 86.8+/
6.90%). Loss of viability was directly related to the length of exposure of the
cultured cells to papaverine. Morphologic changes of cells incubated with saline:
papaverine were also seen including cell retraction and nuclear pyknosis. The
cells exposed to medium recovered 100% viability whereas by 4 hours only 22% of
the saline: papaverine cells were viable, and by 3 days this viability had fallen
to 7.7%. CONCLUSIONS: Loss of viability was shown in cultured saphenous vein
endothelial cells exposed to saline solutions containing papaverine, whereas no
difference was found between culture medium, saline and balanced salt solutions.
Cell death was directly related to the length of exposure of the cells to
papaverine. Further, after short- and long-term recovery periods, there was
little recovery of cell viability. Although papaverine is a potent vasodilator,
exposure to this compound may compromise long-term viability of graft endothelial
cells.
PMID- 9639005
TI - Incidence and risk factors of perioperative cerebral complications. Heart
transplantation compared to coronary artery bypass grafting and valve surgery.
AB - OBJECTIVE: The aim of this study was to define the neurologic risk of heart
transplantation compared to coronary artery bypass grafting (CABG) and valve
surgery. DESIGN: A retrospective study. SETTING: A university hospital. PATIENTS:
8001 patients undergoing heart transplantation, CABG and valve surgery. MEASURES:
The incidences of perioperative central nervous system (CNS) complications were
compared between different procedures. Risk factors were analysed using
univariate and multivariate methods. RESULTS: The overall incidence of CNS
complications was 19.8% (78/393) in heart transplantation, 3.1% (176/5734) in
elective CABG, 9.5% (161/1689) in elective valve surgery, 10.3% (15/146) in
emergency CABG and 51.3% (20/39) in emergency valve surgery. Most powerful
predictors of CNS complications were preoperative intra-aortic counterpulsation
(IABP) in the heart transplantation group, age >65 years in the CABG group and
preoperative use of catecholamine in the valve group. CONCLUSIONS: CNS
complications occur much more frequently after heart transplantation than
elective CABG and valve surgery. The high incidence of CNS complications after
emergency operations as well as preoperative catecholamine and IABP as powerful
contributing factors suggest that preoperative cerebral hypoperfusion due to a
compromised hemodynamic state facilitates postoperative CNS complications and
this may partly explain the high incidence of CNS complications after heart
transplantation.
PMID- 9639006
TI - Early and late results after surgical therapy of postinfarction left ventricular
aneurysm.
AB - From 1979 to 1993, 139 patients had reduction of left ventricular aneurysm (LVA)
by plication (PL) (25 cases) linear repair (74 cases) or ventricular
reconstruction (VR) (40 cases). Coronary bypass grafting was performed in 89
patients. We retrospectively reviewed our experience in order to identify
predictore of early and late outcome and determine whether ventricular
reconstruction (VR) can improve postoperative and late prognosis. Operative
mortality (OM) was 7.2%. Among 129 hospital survivors, 48 died during FU (LM). OM
was related to a more recent myocardial infarction (p=0.0001), a higher residual
score (RS) (p=0.02), a lower EF (p=0.038), a higher left ventricular score
(p=0.059), a three-system disease (TSD) (p=0.09) and a right coronary disease
(RCD) (p=0.13). At Multivariate Analysis (Stepwise Logistic Regression) TSD
(p=0.001), RCD (p=0.008) and RS (p=0.04) are independent risk factors. Actuarial
survival rate at 15 years is 33.5+/-6.9% (OM included). According to the
comparison of the Actuarial Curves (Tests of Mantel and Breslow, OM excluded) the
most significant risk factors were: non use of left internal mammary artery
(LIMA) (p=0.004), VR (p=0.01), TSD (p=0.03) and higher NYHA class (p=0.019).
Multivariate Analysis (Co Model) confirms that late prognosis is influenced by
non use of LIMA (p=0.03) and TSD (p=0.04); outcome is also affected by
preoperative arrhythmias (p=0.022). Five-year survival after VR is 87.5+/-5.7% vs
64.9+/-5.5% after simple linear closure or PL (p=0.1075 and p=0.2252). Our
results confirm that OM and LM are influenced by extent of myocardial ischemic
damage; in agreement with the majority of Authors we advocate a complete
revascularization using IMA, when appropriate, on left anterior descending
artery. Our limited experience with VR fails to demonstrate this technique as an
independent factor of late survival.
PMID- 9639007
TI - Chylous ascites following heart transplantation.
AB - We report a case of chylous ascites in a 52-year-old woman after an orthotopic
heart transplantation. The patient was successfully managed with conservative
treatment including dietetic measures and repeated paracentesis. The potential
aetiopathological factors involved and other implications for cardiac transplant
patients are discussed.
PMID- 9639008
TI - Laceration of a saphenous vein graft by an epicardial pacemaker wire.
AB - The use of temporary pacing wires has become wide-spread in cardiac surgery.
Complications related to their use are rare. We report a case of cardiac
tamponade following removal of an atrial pacing wire.
PMID- 9639009
TI - Echo-guided endomyocardial biopsy in heterotopic heart transplantation. Case
report.
AB - Right ventricular endomyocardial biopsy is difficult to perform in patients who
underwent heterotopic heart transplantation because of the complex vascular
anatomy. The procedure is usually performed under fluoroscopic control. We
present a case of a 59-year-old woman that after heterotopic heart
transplantation underwent echo-guided endomyocardial biopsy. We report the
technique discussing data obtained in other 11 patients heart transplanted in the
heterotopic way. In conclusion we believe that echocardiographic guidance during
endomyocardial biopsy allows a better choice of bite sites, reduces the risk of
free wall perforation. Moreover is diminished the risk of X-ray exposure to both
patient and operator.
PMID- 9639010
TI - Myocardial abscess at a distant zone from the active valvular infection.
AB - A case of an infective endocarditis with myocardial abscess due to Streptococcus
anginosus at a distant location from the active valvular infection is reported.
We conclude that local cardiac suppurative complications can appear in the
evolution of endocarditis caused by this virulent organism.
PMID- 9639011
TI - Bilateral thoracotomy for coronary artery bypass grafting in a patient with
unfavorable median sternotomy.
AB - In this report, we describe a patient who underwent coronary artery bypass
grafting (CABG) through bilateral thoracotomy and distal median sternotomy,
because he had received terminal tracheotomy as a treatment to prevent aspiration
pneumonia due to Wallenberg's syndrome. On the first day after the terminal
tracheotomy, he suddenly complained of severe anterior chest pain. Emergency
coronary angiogram revealed complete occlusion of the proximal right coronary
artery (RCA), severe stenosis of the left anterior descending artery (LAD) and
the large first diagonal branch. Catheter intervention for RCA was attempted but
it was unsuccessful, and therefore he was required to have urgent operation. The
patient had received total laryngectomy and terminal tracheotomy two weeks before
urgent CABG, and the large hole of the tracheotomy was just placed above the
incisura juglaris of the sternum. So high risks of sternal infection and severe
mediastinitis after ordinary median sternotomy were considered and we applied the
bilateral thoracotomy approach. To our knowledge, this is very rare but effective
approach to vascularize both right and left coronary artery and to use both left
internal thoracic artery (LITA) and gastroepiploic artery (GEA) graft. It seemed
that this approach is safe and effective for cardiac surgery in such situations
that median sternotomy is not favorable as in the described patient or in
patients having reoperation.
PMID- 9639012
TI - Immunohistochemical properties of lipid peroxidation and prognosis in
adenocarcinoma of the lung.
AB - Glutathione-related enzymes are thought to influence the prognoses of patients
with adenocarcinoma of the lung. In this study, the localization of these enzymes
was examined immunohistochemically in the primary lesions and metastatic lymph
nodes of 61 patients with primary adenocarcinoma. Strong immunoreactivity for
glutathione peroxidase (GSH-PO) and superoxide dismutase (SOD) was found in
tissue from patients with poor prognoses, while tissue from patients with
favorable prognoses demonstrated only immunoreactivity for these enzymes.
Therefore, believe that glutathione-related enzymes may serve as predictors of
tumor resistance in patients with adenocarcinoma, hence measuring these enzymes
may be useful in determining the need for adjuvant therapy.
PMID- 9639013
TI - Lung volume reduction surgery for emphysema. A review.
AB - Lung volume reduction surgery is emerging as a promising treatment option for
selected patients with severe, debilitating end-stage emphysema refractory to
medical management. Lung volume reduction surgery involves the removal of space
occupying severely diseased, slowly ventilating and hyperexpanded lung, thus
allowing the better conserved adjoining lung parenchyma to expand into the
vacated space and function effectively. The operation can be accomplished by
unilateral or bilateral thoracoscopy, thoracotomy or median sternotomy. The most
emphysematous areas are excised using stapling or laser techniques or both. This
review summarises the results of lung volume reduction surgery performed by
various operative techniques. Results indicate that in the majority of patients
improvement occurs in subjective dyspnoea and objective pulmonary function while
oxygen and steroid dependence are reduced or eliminated at the cost of acceptable
mortality and morbidity. Even though bilateral procedures produced much greater
improvement, it is emphasized that it is the lung resection and not the operative
approach that is critical to the success of the operation. Regardless of the
technique used, the surgical treatment of emphysema is palliative in nature.
PMID- 9639014
TI - Intraoperative cardiac tamponade complicating esophagogastrectomy.
AB - BACKGROUND: Thoracoabdominal esophagogastrectomy is associated with a number of
potential life-threatening complications. PATIENTS: We describe a patient with
intraoperative hypotension in which a number of therapeutic maneuvers eventually
led to the diagnosis of cardiac tamponade. RESULTS: Once the diagnosis of
tamponade was made, it was successfully treated by the release of
intrapericardial blood. CONCLUSIONS: Although rare, tamponade should be
considered as a cause of hemodynamic instability whenever intraoperative
manipulation of the heart has occurred.
PMID- 9639015
TI - Rupture of the azygos vein in blunt chest trauma.
AB - Isolated traumatic laceration of the azygos vein is a rare condition that is
mainly associated with violent deceleration traumas. Diagnosis is crucially based
on radiologic evidence of massive right pleural bleeding and hemorrhagic shock.
Surgical exploration needs to be early and concomitant with resuscitation,
prognosis largely depending on timely intervention. Median sternotomy provides
the most advantageous access because it can be quickly performed and allows for
surgical exploration.
PMID- 9639016
TI - Magnetic resonance angiography in axillobifemoral grafting.
PMID- 9639017
TI - The effect of free-radical-scavenger system "N-Acetylcysteine/Glutathione" for
hypothermic prolonged lung cells preservation.
PMID- 9639018
TI - Regional differences in noradrenaline-induced release of adenosine triphosphate
from rat vascular endothelium.
AB - We examined the release of endogenous adenyl purines such as adenosine
triphosphate (ATP), ADP, AMP and adenosine from the caudal artery (CA), saphenous
artery (SA), renal artery (RA), mesenteric artery (MA), pulmonary artery (PA) and
thoracic aorta (TA) of rats, using high-performance liquid chromatography
fluorescence detection. Noradrenaline induced the release of adenyl purines from
these blood vessels. The total amount of adenyl purines release induced by
noradrenaline from the CA was considerably larger than that from the TA. The rank
order of the amount of adenyl purines released from the six blood vessels was
CA>SA>RA>MA>PA> or =TA. The noradrenaline induced release of adenyl purines from
the CA was significantly reduced by the removal of the endothelium. Noradrenaline
also induced the release of adenyl purines from cultured endothelial cells of the
CA and TA. The total amount of adenyl purines released from the former blood
vessel was much larger than that from the latter. These results suggest the
existence of vascular endothelial cells that are able to release ATP by an alpha1
adrenoceptor mediated mechanism, and that these cells are not homogeneously
distributed in the vasculature.
PMID- 9639019
TI - Involvement of cholinergic motor neurons in pharmacological regulation of
gastrointestinal motility by glucagon in conscious dogs.
AB - To clarify the exact mechanisms of the pharmacological effects of glucagon on
gastrointestinal motility, the following experiments were performed on the
conscious and anesthetized dogs. 1) During phase I of interdigestive migrating
contractions (IMC), glucagon (5 approximately 50 microg/kg, drip infusion for 5
minutes) induced phasic contractions in the duodenum, jejunum and ileum, but not
in the antrum. These excitatory responses were also observed in the truncal
vagotomized dogs. These contractions were abolished by atropine or hexamethonium
in the conscious dogs, and also by tetrodotoxin in the anesthetized dogs. 2)
Glucagon inhibited cisapride-induced contractions only in the antrum in the
conscious dogs. After pre treatment with hexamethonium, glucagon inhibited these
contractions in the duodenum, jejunum and ileum as well as in the antrum. After
pre treatment with tetrodotoxin in the anesthetized dogs, glucagon did not affect
acetylcholine induced contractions in any region. 3) Glucagon inhibited
spontaneous phase III contractions and erythromycin induced phase III like
contractions in the antrum, but did not inhibit either contractions in the other
regions in the conscious dogs. These paradoxical effects of glucagon between the
antrum and intestine were similar to those involved in the blockade of 5
hydroxytryptamine 3 receptors. After pre-treatment with hexamethonium, glucagon
inhibited these contractions in the duodenum, jejunum and ileum as well as in the
antrum. IN CONCLUSION: 1) Glucagon latently inhibits cholinergic motor activities
in the antrum and intestine not directly, by binding to either receptor on the
smooth muscle cells, but through postganglionic cholinergic neurons and possibly
through 5-hydroxytryptamine neurons. 2) On the other hand, in the intestine the
reverse effects through preganglionic cholinergic neurons involving nicotinic and
muscarinic receptors are more potent. 3) As a result, glucagon inhibits antral
contractions and does not affect intestinal contractions in a conscious state.
PMID- 9639020
TI - Essential role of newly synthesized ATP for cyclic GMP-induced relaxation in
alpha-toxin permeabilized smooth muscle of rat proximal colon.
AB - The role of newly synthesized ATP in cyclic GMP-induced relaxation was studied in
membrane permeabilized longitudinal muscle preparations of the rat proximal
colon. Cyclic GMP and 8 bromo cGMP induced concentration-dependent relaxation of
alpha-toxin permeabilized preparations which were precontracted by 3 microM Ca2+
in the presence of 4 mM ATP and 5 mM phosphocreatine (PC). The relaxation by 8
bromo cGMP was inhibited by Rp-8-pCPT cGMPS, an inhibitor of cyclic GMP dependent
protein kinase. The relaxation was inhibited by removal of PC from the bathing
solution, in spite of the presence of ATP. The relaxation was also inhibited by
dinitrofluorobenzene (DNFB), a selective inhibitor of creatine kinase. The
removal of PC or treatment with DNFB is known to produce accumulation of ADP
within smooth muscle cell, however, ADPbetaS did not affect the relaxation. After
irreversible inhibition of endogenous creatine kinase by DNFB in beta-escin
permeabilized preparations, treatment of the preparations with exogenous creatine
kinase restored the relaxation. In the presence of ADP and PC but without ATP, 8
bromo cGMP induced the relaxation to the similar extent to that in the presence
of ATP and PC. These results suggest that ATP newly synthesized from ADP and PC
by creatine kinase is essential for cyclic GMP-induced relaxation of the smooth
muscle preparations obtained from the proximal colon of rats.
PMID- 9639021
TI - Muscarinic inhibition of L-type Ca2+ channels in guinea-pig tracheal smooth
muscle cells.
AB - Modulation of L-type Ca2+ channels by acetylcholine (ACh) was studied in
enzymatically isolated guinea-pig tracheal smooth muscle cells (TSMCs). ACh
reversibly inhibited whole cell L type Ca2+ current measured with Ba2+ ions as
charge carriers (I(Ba)). With pipette solution containing 0.1 mM EGTA, 1 microM
ACh induced transient inhibition of I(Ba) followed by sustained inhibition
(67.0+/-3.7% of the control, n=19). When intracellular Ca2+ concentration
([Ca2+]i) was fixed at 50 nM by BAPTA-Ca2+ buffer in the pipette, the transient
inhibition was abolished whereas the sustained inhibition (66.0+/-7.8%, n=6)
still occurred, suggesting that the transient inhibition was attributed to
inactivation of the channels induced by increase in [Ca2+]i. The sustained
inhibition was abolished when [Ca2+]i was fixed at zero. The sustained inhibition
of I(Ba) by 1 microM ACh was observed in the presence of 10 microM AF-DX 116,
whereas it was not observed in the presence of 1 microM 4 DAMP. ACh did not
inhibit I(Ba) in the presence of 1 mM GDP-beta-S in the pipette, whereas the drug
irreversibly inhibited the current in the presence of 0.1 mM GTP-gamma-S in the
pipette. Pretreatment of TSMCs with pertussis toxin did not altered the effects
of ACh. Application of neither 1-oleoyl-2-acetyl sn-glycerol (1 microM) nor
phorbol 12-myristate 13-acetate (1 microM) reduced I(Ba). These results suggest
that the sustained inhibition of I(Ba) by ACh is mediated by Ca2+ requiring and
protein kinase C-independent mechanisms existing in the downstream of G-protein
coupled with M3 receptors.
PMID- 9639022
TI - Pharmacological regulation of postprandial gastrointestinal motility by glucagon
in conscious dogs.
AB - The physiological or pharmacological role of glucagon in the postprandial
regulation of gastrointestinal motility has not yet been clarified. To clarify
it, the following experiments were performed on conscious dogs. Antral, duodenal,
jejunal and ileal contractile activities were monitored by chronically implanted
strain gauge force transducers without restraint. The serum gastrin concentration
in response to ingestion was measured by radioimmunoassay. 1) When glucagon (5
approximately 50 microg/kg, drip infusion for 5 minutes) was administered before
ingestion of meal or 2 hours after ingestion, it inhibited postprandial motility
dose-dependently in the antrum, while enhancing it in the duodenum, jejunum and
ileum. 2) At the same time, glucagon inhibited the meal induced elevation of the
serum gastrin concentration. 3) On the other hand, glucagon did not inhibit the
contractions induced by pentagastrin (4 microg/kg,s.c.) or those induced by
acetylcholine chloride (0.5 mg/kg, drip infusion for 10 minutes) in any region.
4) These glucagon-induced inhibitory effects in postprandial antral motility were
not affected by phentolamine (0.5 mg/kg, i.v.) or nitro-L-arginine-methyl ester
(L-NAME) (3 mg/kg/hr, drip infusion for 30 minutes). These results suggest that:
1) Glucagon inhibits the postprandial elevation of the serum gastrin
concentration and thus inhibits postprandial antral motility. 2) On the other
hand, in the intestine, glucagon-induced inhibitory responses might be reversed
by glucagon-induced excitatory responses through preganglionic cholinergic motor
neurons. 3) The mechanism of inhibition of gastrin release was not definite in my
experiments, but one of the candidates may be activation of somatostatin release
from the D cells by glucagon.
PMID- 9639023
TI - Postprandial electrogastrographic changes with or without parasympathetic nerve
blockade.
AB - To investigate the relationship between postprandial electrogastrographic changes
and parasympathetic nervous activity, 10 healthy adult males (20 to 29 years old)
volunteered for EGG recording in the following conditions: 1) butylscopolamine
bromide (scopolamine) administration to block parasympathetic nervous activity;
2) after food intake; and 3) during a postprandial period after the
parasympathetic blockade. Power spectral analysis of EGG was performed according
to Akaike's autoregressive model. When the parasympathetic nervous activity was
blocked, there were no changes in the dominant frequency of the EGG. During the
postprandial period, the dominant frequency in EGG increased significantly, and
postprandial dip (transient frequency decrease after the food intake) was
observed in 8 of the 10 subjects. During the postprandial period after
scopolamine administration, the dominant frequency of EGG did not increase, and
postprandial dip was observed in only two subjects. These results suggest that
the parasympathetic nervous activity is involved in occurrence of postprandial
gastric motor function and postprandial electrogastrographic changes.
PMID- 9639024
TI - Imaging of calcium release in inositol 1,4,5-trisphosphate-sensitive internal
stores in permeabilized HSY cells using fluorescent indicators.
AB - We described methods for imaging the IP3-induced Ca2+ release in Ca2+ storage
organelles. IP3-induced changes in Ca2+ concentrations within Ca2+ stores
([Ca2+]L) in permeabilized HSY cells were monitored using the low affinity Ca2+
indicators, mag-fura-2 and mag-fura-red. The ratio images of mag-fura-2 were used
to estimate the [Ca2+]L in the store. The apparent [Ca2+]L was 300-1000 microM at
the cell periphery, whereas the [Ca2+]L in the cytoplasm around the nucleus was
70-150 microM. The [Ca2+]L throughout the cytoplasm was reduced by the
application of 10 microM IP3 to 30-70 microM, and could be largely recovered
after removal of IP3. The structure of IP3-sensitive Ca2+ stores was investigated
by confocal microscopy using mag-fura-red. An IP3-induced increase in
fluorescence was observed in the ER-like network and reticulum structures of the
cytoplasm, and also in the nuclear envelope, suggesting that these organelles
serve as IP3-sensitive Ca2+ stores. An analogous localization of the network and
tubular elements of the ER was also demonstrated by electron microscopy. These
observations suggest that these fluorescence techniques are useful to study the
correlation between the distribution and function of Ca2+ stores.
PMID- 9639025
TI - Localization of cytoplasmic dynein light-intermediate chain mRNA in the rat
testis using in situ hybridization.
AB - Expression of cytoplasmic dynein light-intermediate chain mRNA in the rat testis
was examined using in situ hybridization. The ribonucleotide probe, referred to
the 5' end of open reading frame (6-515 nucleotids) of cytoplasmic dynein light
intermediate chain 53/55 (LIC-2) of the rat brain (Hughes et al., 1995. J. Cell
Sci., 108: 17-24), was used. All spermatogenic cells were positive. Pachytene
spermatocytes in later stages (after-stage VII) were the most intensely positive
and round spermatids were also intense. These findings indicated that all
spermatogenic cells may store the light-intermediate chain signal, and
spermatocytes may produce it during later stages. The reaction in Sertoli cells
was constant in intensity during the spermatogenic cycle, indicating that the
light-intermediate chain mRNA signal may have no relation to the stage-dependent
organelle transport, and that there may be post-translational regulation of the
light-intermediate chain. In interstitium, only a few positive cells were
observed. Northern blot hybridization demonstrated that one major band (2.0 kb)
and two minor bands (4.4 kb and 3.5 kb) were detected in the testis, while one
major band (4.4 kb) and one minor band (3.5 kb) were in the brain. This indicated
that there are at least 3 isoforms in cytoplasmic dynein light-intermediate chain
53/55.
PMID- 9639026
TI - Immunocytochemical detection of phosphatidylinositol 3 kinase in Burkitt lymphoma
cells.
AB - PI 3-kinase, an enzyme responsible for the phosphorylation of the D3 position of
the inositol ring of phosphatidylinositol (PI), is recognized to be involved in
the regulation of many cellular processes such as mitogenic signalling,
inhibition of apoptosis, intracellular vesicle trafficking/secretion, regulation
of actin and integrin functions and regulation of protein kinases induced by
tumour necrosis factor, oncoproteins and ultraviolet light. Here we report the
subcellular distribution and the phosphorylative pattern of p85 alpha subunit of
PI 3-kinase in Burkitt lymphoma cells exposed to R interferon alpha treatment.
Immunocytochemical analysis of this enzyme, performed by confocal microscopy,
revealed an increased expression of this protein at cytoplasmic level after 90
min of interferon alpha treatment. Western blotting analyses performed on nuclear
and cytoplasmic fractions confirmed the overexpression found by confocal
microscopy at cytoplasmic level in the 90 min interferon alpha treated cells
still persisting in the 24 hr treated samples. Such an overexpression was
paralleled by an increase of tyrosine phosphorylation both at cytoplasmic and
nuclear level suggesting that an enhanced requirement for cytoplasmic expression
and phosphorylation of PI 3-kinase might be necessary to the cell for regulating
some cytoplasmic-nuclear cross talk involved in the control of Burkitt lymphoma
cell metabolism following interferon alpha treatment.
PMID- 9639027
TI - TATA-less mouse vitronectin gene promoter: characterization of the
transcriptional regulatory elements and a nuclear protein binding site on the
promoter.
AB - Vitronectin in a cell-adhesion molecule whose expression is temporally and
spatially regulated in vivo, but whose regulatory mechanism of transcription is
unknown. In this study, we characterized the mouse vitronectin gene promoter.
Luciferase expression vectors cloned the successive 5'- or 3'-deletions of the 5'
flanking region upstream of the luciferase gene and were transfected into the
human hepatoma cell line HepG2. The assay of luciferase activity in the
transfected cells revealed that a 38 base pair (bp)-element (positions +3 to +40)
displays promoter activity. A consensus sequence consisting of a TATA box and
initiator is shown around the transcription initiation site of the mouse
vetronectin gene, but the GC box is not shown. Site-directed or deleted
mutagenesis against a consensus sequence of TATA box and initiator could not
abolish the promoter activity. These results induce that the putative TATA box
and initiator are not involved in the promoter activity, and that the vitronectin
promoter lacks the TATA box, initiator and GC box. To characterize trans-acting
factors involved in promoter activity, a DNA fragment (position -74 to +95) was
subjected to gel shift assay using nuclear proteins extracted from HepG2 cells.
One shifted band was detected by the gel shift assay, suggesting that a nuclear
protein binds to the promoter region. Results of the DNase I foot printing assay
and gel shift assay demonstrate that the nuclear proteins can bind to the 38 bp
element, which has promoter activity. The nuclear protein is a putative trans
acting factor involved in transcription initiation.
PMID- 9639028
TI - Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion
between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells.
AB - We studied the effects of bafilomycin A1, a potent and specific inhibitor of
vacuolar H+ ATPase (V-ATPase), on the process of autophagy in rat hepatoma cell
line, H-4-II-E cells. To induce autophagy, cells were transferred from Dulbecco's
modified Eagle medium containing 12% fetal calf serum into Hanks' balanced salt
solution. When bafilomycin A1 was added to Hanks' balanced salt solution,
endogenous protein degradation was strongly inhibited and numerous autophagosomes
accumulated in H-4-II-E cells, whereas autolysosomes decreased in number. Acid
phosphatase activity was not detected in the autophagosomes which accumulated in
the presence of bafilomycin A1, suggesting that fusion between autophagosomes and
lysosomes was disturbed by this drug. Inhibition of the fusion was reversible,
and the autophagosomes changed into autolysosomes after the removal of the
inhibitor. Bafilomycin A1 also prevented the appearance of endocytosed HRP in
autophagic vacuoles. These results suggested that acidification of the lumenal
space of autophagosomes or lysosomes by V-ATPase is important for the fusion
between autophagosomes and lysosomes.
PMID- 9639029
TI - Structural analysis of milk and testis beta-1,4-galactosyltransferase gene
products.
AB - There seems to exist a relatively low similarity between the amino acid sequences
of the testis and milk beta-1,4-galactosyltransferase gene products. However, the
predicted higher structures of testis and milk beta-1,4-galactosyltransferase
proteins revealed a highly significant similarity in the regions required for
enzymatic activities. Testis beta-1,4-galactosyltransferase protein contained a
WD repeat similar to the motif of the G protein beta subunit type I and a Zn
finger motif at the N- and C-terminal portions of the protein, respectively.
Phylogenetic analysis of glycosyltransferase proteins revealed that the ancestral
gene of testis and milk beta-1,4-galactosyltransferases and alpha-1,3
galactosyltransferase evolved into three different destinations at about the same
time on an evolutionary scale.
PMID- 9639030
TI - A stereotaxic atlas of the grey lesser mouse lemur brain (Microcebus murinus).
AB - In response to the growing interest in the prosimian Microcebus murinus for
studies on cerebral aging, the stereotaxic atlas of its brain was carried out in
view of further anatomical, biochemical, electrophysiological, and behavioral
investigations as well as for therapeutic experiments. This primate, which could
be a valuable model for neuroscientific studies in various domains, presents
numerous physiological advantages (e.g., size, cost, and ability to breed)
compared to rodents, which can be used as nonprimate models, and simians. The
atlas, valid for adult microcebes of every age and both sexes, consists of 54
frontal plates and 28 sagittal plates. For the establishment of stereotaxic
coordinates and for drawings and photographs, 10 adult specimens of Microcebus
murinus were used. The brains were frozen, cut into sections of 50 microm
thickness, every fourth section being stained with Nissl. First, sections were
projected and the outlines of the different structures, nuclei, and fibers were
drawn. Then, the accuracy of the analysis was improved by detailed observation
directly by microscope and also by computer analysis. Finally, the photographs of
the sections were scanned and processed using the software Photoshop and
Illustrator. For testing coordinates, several verifications were made.
Experiments on lesions and injections of different substances were carried out in
specific regions of the brain and brains implanted with needles were fixed in
formol and embedded in paraffin wax.
PMID- 9639031
TI - The calcium receptor in health and disease.
AB - The recent cloning of a G-protein-coupled, extracellular calcium [(Ca2+)e]
sensing receptor (CaRG) from the parathyroid, kidney and brain of several species
has clarified the molecular mechanisms underlying Ca2+-sensing by parathyroid and
other cell types. It has long been suspected that such a receptor existed on
parathyroid cells, coupled to intracellular second messengers through guanine
nucleotide regulatory (G) protein which is able to recognize and respond to
(Ca2+)e. Recently, functional screening of a cDNA library constructed from bovine
parathyroid mRNA led to the isolation of a 5.3-kb clone expressing maximal Ca2+
stimulated Cl- currents in oocytes. This 5.3-kb cDNA encodes a protein of 1,085
amino acids with three principal predicted structural domains. The CaRG protein
is present in chief parathyroid cells, in C cells of the thyroid, in the cortical
thick ascending limb (TAL) and collecting duct of the kidney, and in discrete
brain areas. CaRG may play several physiological roles. It is a central element
in the control of both parathyroid and calcitonin secretion by (Ca2+)e. Moreover,
functional evidence for its participation in the regulation of renal Ca2+
reabsorption in TAL and water reabsorption in the collecting duct has been
obtained. Mutations of the CaRG gene are responsible for hereditary and familial
parathyroid disorders, and a decrease in CaRG expression has been documented in
primary and secondary uremic hyperparathyroidism. The expression of CaRG in
several additional organs and tissues allows speculation on the potential
involvement in other pathologies.
PMID- 9639032
TI - Prostaglandin receptors in the kidney: a new route for intervention?
AB - Prostaglandins comprise a structurally diverse family of cyclooxygenase
metabolites of arachidonic acid, including thromboxane A2, PGD2, PGE2, PGF2alpha
and PGI2. These prostaglandins are now known to act via different G-protein
coupled receptors. PGE2, the major prostaglandin synthesized along the nephron,
interacts with at least four E-prostanoid (EP) receptors, three of which are
highly expressed in distinct regions of the kidney. Each EP receptor also
preferentially couples to a different signal transduction pathway, including
stimulation of cAMP generation by the EP2 and EP4 receptors; inhibition of cAMP
generation, via Gi by EP3 receptors, and activation of phosphatidylinositol
hydrolysis by EP1 receptor. Other intrarenal prostanoid receptors include the
thromboxane A2 receptor and the prostacyclin receptor. These receptors also
exhibit a discrete intrarenal distribution. The possibility of pharmacologically
targeting each renal prostanoid receptor may provide a unique approach to
modifying renal function in disease states.
PMID- 9639033
TI - Adeno-associated virus gene transfer into renal cells: potential for in vivo gene
delivery.
AB - The human parvovirus adeno-associated virus (AAV), type 2, has a number of
features that make it an attractive choice as a vector for gene delivery to the
kidney. AAV vectors permit long-term gene expression in vivo by integration into
the host genome, have potential for site-specific integration on chromosome 19,
do not express viral genes or generate a cellular immune response, and
demonstrate enhancement of gene expression by chemotherapeutic agents that are
approved for use in vivo. These properties confer advantages to AAV over other
viral and nonviral methods for gene transfer. Preliminary experiments in our
laboratory suggest that AAV is able to transfer genes to both renal cells in
culture and the kidney in vivo. Thus, AAV has the potential to be an important
gene transfer vector for the kidney in vivo.
PMID- 9639034
TI - Endogenous inhibitors of nitric oxide synthesis: how important are they?
AB - In animals and humans, inhibition of nitric oxide (NO) production has widespread
effects. Reduced activity of the NO:cyclic GMP pathway has been documented in
disease states, including hypertension, diabetes and certain types of renal
disease. Inhibitors of NO synthesis occur endogenously, and have been implicated
in the regulation of the NO pathway in health and disease. Here we review the
possible biological roles of endogenous NO synthase inhibitors, with particular
reference to renal disease.
PMID- 9639035
TI - Potential functional roles of extracellular ATP in kidney and urinary tract.
AB - P2 receptors are sensitive to adenosine triphosphate (ATP) and uridine
triphosphate and can be divided into two major subtypes: P2X and P2Y receptors.
They are specific membrane-bound receptors which when activated by extracellular
ATP initiate a variety of biological effects. The P2X receptors are ligand-gated
channels, whereas the P2Y receptors are coupled to G proteins linked to second
messenger systems. In this review, the potential functional roles of
extracellular ATP in the kidney and lower urinary tract are discussed and briefly
explored in the context of some specific renal and urinary tract abnormalities.
PMID- 9639036
TI - Production of inflammatory mediators and cytokine responsiveness of an SV40
transformed human proximal tubular epithelial cell line.
AB - Proximal tubular epithelial cells (PTEC) play a central role in the physiology of
the renal tubulointerstitium. To be able to study the relationship between
tubular cells and inflammatory renal diseases the availability of cultured cells
is of importance. This study describes an immortalized proximal tubular
epithelial cell line which was generated using SV40 DNA. To determine whether the
transformation altered the cell line, the transformed cell line was characterized
phenotypically using different monoclonal antibodies directed against peptidases,
which are characteristic of PTEC, such as adenosine deaminase binding protein
(CD26), leucine amino peptidase and carboxy peptidase M by immunofluorescent
staining and FACS analysis. All peptidases were clearly present on the parental
cell line and the transformed cell line. However, the level of expression of the
peptidases was lower on the transformed cell line as compared to the parental
nontransfected cells. The morphology of the transformed cell line, determined
using a transwell culture system and electron microscopy, showed a polarized
morphology of the tubular cells, tight junctions and microvilli. The transformed
cell line was compared with the parental proximal tubular epithelial cells in its
ability to respond to inflammatory cytokines such as IL- 1alpha TNF-alpha, IFN
gamma. Stimulation with these cytokines resulted in enhanced production of
complement components C2, C3, C4 and factor H, IL-6 and the chemokines IL-8 and
MCP-1. The transformed cell line responded in a similar fashion as the parental
cell line, although the amount of the different proteins produced was
significantly higher in the transformed cell line. Overall, the transformed
tubular cell line seems to be a suitable model to study different effects on
tubular cells in relation to inflammatory kidney diseases.
PMID- 9639037
TI - Expression of cytoskeletal proteins differentiates between progressors and non
progressors in treated idiopathic membranous nephropathy.
AB - Myofibroblasts play an important role in wound healing in a variety of tissue
injuries. They have also been implicated in tissue fibrosis including renal
scarring. This study was aimed at defining their role in one of the commonest
forms of nephrotic syndrome in adults, namely membranous nephropathy. We have
studied 21 patients with biopsy proven idiopathic membranous nephropathy who were
treated with glucocorticoids, attempting to define the role of myofibroblasts
(alpha-smooth muscle actin-positive as well as vimentin-positive cells) in the
progression of this form of nephropathy. There were 13 non-progressors (NP) and 8
progressors (P). The clinical, histological, and immunohistochemical
characteristics of both groups were compared. Immunohistochemical staining for
myofibroblasts cytoplasmic markers a-smooth muscle actin (alpha-SMA) and vimentin
relied on an avidin-biotin-peroxidase method. The level of blood pressure, degree
of proteinuria, severity of interstitial infiltrate and interstitial fibrosis did
not differentiate P from NP. However, vascular sclerosis was more severe in P
compared to NP (p < 0.016) and its severity predicted the subsequent functional
outcome (slope of the 1/serum creatinine against time; r2 = 0.618, p < 0.01).
Mesangial alpha-SMA was significantly higher in P (31 +/- 18.6%) than in NP (14.5
+/- 9.8%), p < 0.015. Interstitial alpha-SMA immunostain was also higher in P but
did not reach statistical significance. However, the number of interstitial
myofibroblasts (alpha-SMA positive cells) closely predicted the subsequent rate
of the progression of chronic renal failure (r2 = 0.919, p < 0.0001). Mesangial
vimentin expression was not different between both groups. By contrast,
interstitial vimentin immunostain was higher in P (19.1 +/- 8.8%) compared to NP
(7.9+/-5.6 %), p < 0.002. These data suggest that the expression of mesangial and
interstitial cytoskeletal proteins (alpha-SMA and vimentin) may have useful
prognostic implications as they appear to differentiate between patients with
membranous nephropathy who respond to immunosuppression and those who continue to
progress.
PMID- 9639038
TI - The renal TGF-beta system in the db/db mouse model of diabetic nephropathy.
AB - The prosclerotic cytokine transforming growth factor beta 1 (TGF-beta1) has been
causally implicated in renal pathobiology in diabetes. We sought evidence that
the TGF-beta system participates in the nephropathic process in the db/db mouse,
a hyperinsulinemic model of genetic diabetes that develops abnormalities in renal
morphology and function that parallel those in human diabetic nephropathy. In
support of this hypothesis, we found that steady state levels of mRNA encoding
the TGF-beta type II receptor were significantly increased in renal cortex from
db/db diabetic mice. Additionally, the translated TGF-beta type II receptor
protein, assessed by immunoblot, also was increased in diabetic kidneys. However,
in contrast to rodents with insulin-deficient diabetes, steady state levels of
mRNA encoding TGF-beta1 in the renal cortex of diabetic db/db mice did not differ
from those in cortex from nondiabetic (db/m) littermate controls. Further,
concentrations of TGF-beta protein, measured by immunoassay and bioassay, were
significantly lower in extracts prepared from renal cortex of diabetic animals
compared with those from nondiabetic controls. Urine and serum concentrations of
immunoreactive TGF-beta1 also were reduced in diabetic mice. The findings are
consistent with upregulation of TGF-beta type II receptor activity as a
consequence of hyperglycemia in the hyperinsulinemic db/db mouse and suggest that
hyperinsulinemia inhibits TGF-beta1 production. The results further suggest that
type II receptor upregulation is a contributing factor to the increased gene
expression of renal cortical mRNAs encoding the extracellular matrix proteins
fibronectin and alpha 1 (IV) collagen and to the renal abnormalities observed in
this animal model.
PMID- 9639039
TI - Podocyte phenotypes as defined by expression and distribution of GLEPP1 in the
developing glomerulus and in nephrotic glomeruli from MCD, CNF, and FSGS. A
dedifferentiation hypothesis for the nephrotic syndrome.
AB - Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein
tyrosine phosphatase located on the apical cell membrane of visceral glomerular
epithelial cell (VGEC) foot processes. Double label immunofluorescence,
immunoelectron microscopy, and peroxidase immunohistochemistry were used to map
the GLEPP1 distribution in the developing glomerulus and in minimal-change
nephropathy (MCN), congenital nephrotic syndrome of the Finnish type, and focal
segmental glomerulosclerosis (FSGS). In MCN GLEPP1 was shifted away from the
glomerular basement membrane on the apical cell membrane of effaced foot
processes. These data are compatible with the previously suggested concept that
MCN can be considered a form of dedifferentiation of the podocyte phenotype.
Similarly, changes seen in congenital nephrotic syndrome of the Finnish type can
be considered a consequence of failure to complete normal podocyte development.
In FSGS glomeruli GLEPP1 was frequently absent from VGECs, even when no sclerosis
was detectable in that glomerulus. Therefore, in FSGS, VGECs may lose GLEPP1, and
this loss appears to occur in the absence of scarring and may, therefore, precede
the scarring process. We speculate that a changed VGEC phenotype that does not
express GLEPP1 might have properties similar to the early undifferentiated VGEC
developmental phenotype. GLEPP1 distribution pattern and absence from glomeruli
of individuals with nephrotic syndrome may, therefore, represent a useful
phenotypic marker.
PMID- 9639040
TI - Renal hemodynamic response to erythropoietin-induced polycythemia in 5/6
nephrectomised rats is different from normal rats.
AB - The effects of recombinant human erythropoietin (rHuEPO)-induced polycythemia on
renal function and glomerular hemodynamics were evaluated in Munich-Wistar rats
(MW+EPO) before and after infusion of indomethacin; the rHuEPO effects on total
renal function were also evaluated in 5/6 nephrectomized (CRF) MW and
spontaneously hypertensive rats (MW-CRF+EPO and SHR-CRF+EPO, respectively). In
normal MW rats, rHuEPO (300 IU/kg BW, 3 x /week, during 2 weeks) induced
elevation in MAP, with maintenance of GFR, paralleled by superficial
vasodilatation and elevation in SNGFR, suggesting cortical blood redistribution.
These hemodynamic alterations induced by rHuEPO were blunted by indomethacin,
suggesting a participation of the vasodilator prostaglandins in the renal
compensatory mechanism of polycythemia. Elevation in MAP and reduction in GFR
occurred in the MW-CRF+EPO group compared with the group receiving vehicle. In
contrast, the SHR-CRF+EPO presented a reduction in MAP and maintenance of GFR,
suggesting different rHuEPO effects depending on previous renal function and/or
hypertensive state.
PMID- 9639041
TI - Expression of Id-1 mRNA and protein in the post-ischemic regenerating rat kidney.
AB - The basic helix-loop-helix (bHLH) class of proteins are of major importance in
controlling tissue-specific gene expression. The actions of the bHLH proteins are
inhibited by a related class of proteins, inhibitors of differentiation (Id). We
have studied the expression of one of these latter proteins, Id-1, in the normal
and post-ischemic regenerating rat kidney by immunocytochemistry, Western blot
and RNase protection assay (RPA) and correlated Id-1 regulation to the expression
of vimentin and proliferating cellular nuclear antigen (PCNA). In the normal
kidney strong immunostaining for Id-1 was found in the distal nephron, especially
in the distal convoluted tubule in the cortex. In particular, the perinuclear
region was intensely stained in the cells of the distal tubule. mRNA for Id-1I
was detectable by RPA on total RNA extracted from the renal cortex of sham
operated animals. The Id-1 monomer was detected on Western blots of normal
animals. Vimentin was expressed in the mesangial cells of the glomeruli and in
cells in the interstitium while tubule cells were negative. The labeling
intensity for PCNA was low in all cellular compartments in the normal kidney. In
the regenerating kidneys at various time intervals, the expression of Id-1-like
immunoreactivity was widespread in the regenerating dedifferentiated tubule cells
while by the end of the study period, more highly differentiated tubule cells
appeared to lose their staining. On Western blots the Id-1 monomer was
undetectable and instead strong staining was seen in the high molecular range. Id
1 mRNA levels in the regenerating kidneys did not differ significantly when
compared to sham. PCNA labeling was intense in the regenerating kidneys at all
time periods studied, indicating the intense proliferative activity in the
regenerating kidneys. Vimentin expression in the renal tubule cells was increased
from day 3 and onward. The data are consistent with a hypothesis in which Id-1
regulates differentiation of renal tubule cells in the post-ischemic regenerating
rat kidney.
PMID- 9639042
TI - Y-chromosome deletions and male infertility: state of the art and clinical
implications.
PMID- 9639043
TI - The acid-fast stain is a superior stain for use in the mean mature spermatid
count for testicular biopsies.
AB - The mean mature spermatid count (MMSC) provides a useful, simplified quantitative
evaluation of human spermatogenesis that is based on the number of mature
spermatids in histological sections of testicular biopsies. Here, the activity of
the acid-fast (AF) stain was compared to that of the usual hematoxylin and eosin
(H&E) stain in performing the MMSC. Thirty bilateral testicular biopsies showing
normal spermatogenesis were chosen retrospectively from 15 subfertile patients
with obstructive azoospermia or severe oligospermia. The MMSC was determined on
each biopsy by utilizing both H&E and AF stains. The AF stain proved to be
specific for the mature spermatids normally counted for the MMSC. It simplified
recognition of mature spermatids, thereby shortening the overall time required
for the procedure. The mean AF MMSC was lower than the mean H&E MMSC, and the
mean interobserver differences were decreased. The AF stain is a superior stain
for the MMSC when used in conjunction with the H&E stain for descriptive
histology.
PMID- 9639044
TI - Vitamin E deficiency causes incomplete spermatogenesis and affects the structural
differentiation of epithelial cells of the epididymis in the rat.
AB - The effects of vitamin E deficiency on the rat testis and epididymis were
examined in a light- and electron-microscopic analysis. Various groups of animals
were made vitamin E-deficient, beginning at postnatal day 10, via their lactating
mothers, until day 21, when they were separated from their mothers. The groups
were maintained thereafter on either a vitamin E-deficient or a normal diet
(controls). The vitamin E-deficient animals of group A, sacrificed at day 42,
revealed testes that were normal in appearance, with a full complement of germ
cells when compared to their controls (group B). Group C, however, sacrificed at
day 48, revealed major abnormalities in the testes, unlike both their controls
(group D) and normal, untreated animals (group E). Spermatogenesis was
incomplete; the most advanced cell type was predominantly step-7 spermatids.
However, many of these cells, as well as earlier spermatids, appeared to undergo
degeneration, evidenced by large pale areas in their nuclei, disrupted acrosomes,
and a cytoplasm with uncharacteristic organelles. Multinucleated cells,
characterized by their chromatoid bodies as spermatids, were often seen in the
seminiferous tubule lumen. Sertoli cells were normal in appearance, except for
numerous, large lipid droplets in their basal region, at stages I-VIII; in
appropriate controls (group D), such droplets were absent at these stages. These
lipid inclusions presumably represented the final breakdown products of the late
spermatids, which were phagocytosed by Sertoli cells between days 42 and 48.
However, numerous germ cells, often recognized as round spermatids, and
multinucleated cells were noted in the epididymal lumen, which indicates that
such cells were spared from Sertoli cell phagocytosis. These data suggest that
vitamin E plays a key role in the maintenance and survival of spermatids. In the
epididymis, vitamin E deficiency resulted in principal, narrow, and apical cells
that showed a poorly developed secretory and endocytic apparatus at days 42
(group A) and 48 (group C), unlike those of normal, untreated animals (group E).
On the other hand, clear cells of groups A and C showed a highly developed
endocytic apparatus in the cauda region only, whereas in the caput and corpus
regions, endocytic apparatuses were small and undifferentiated, unlike those of
group E. Thus, in the epididymis, vitamin E plays a role in the structural
differentiation of principal cells along the entire epididymis, whereas, in the
case of clear cells, its role is region-specific. Readministration of vitamin E
to the diet restored a normal appearance to both the testis and the epididymis,
which indicates that the effects on these tissues are reversible. Taken together,
these data indicate that vitamin E plays important roles in maintaining the
viability of the spermatid population and in allowing epithelial epididymal cells
to acquire their fully differentiated structural appearance.
PMID- 9639045
TI - Activation of coagulation factor X in human semen.
AB - Tissue factor (TF) is an essential cofactor for factor VII (fVII) in initiating
blood coagulation. Recently, TF was shown to be present in human semen and to be
associated with prostasomes that originate from prostatic secretions. In the
blood coagulation cascade, the complex of TF and activated factor VII (fVIIa) can
activate both factor X and factor IX, by limited proteolysis. In the present
study, we investigated the ability of semen to activate factor X. We also
determined that factor X was activated predominantly by TF-fVIIa and that most of
the TF was present in the seminal plasma, consistent with prostasome
localization. No endogenous factor X was detected in semen, but activation of
added factor X occurred in the absence of added fVIIa. Subsequent experiments
showed that seminal plasma contains endogenous fVII-like activity, but the
addition of more fVIIa increased factor X activation. Thus, while seminal plasma
contains significant amounts of TF, its potential to activate factor X is limited
by fVII availability and by the absence of endogenous factor X. Evaluation of
semen specimens from infertility patients revealed a 16-fold variation in TF-fVII
activity. No relationship between TF and number of days of abstinence, specimen
pH, sperm count, or sperm motility was evident. Additional factor X-activating
potential, independent of further TF activity, was generated in seminal plasma
after treatment of semen with calcium and ionophore A23187. Production of this
additional activity was blocked by the addition of anti-TF antibody during the
activation. Since there is no factor X endogenous to semen, the additional
activity stimulated by A23187 appears to be due to an endogenous, non-factor X
substrate for TF-fVII in semen. This endogenous substrate may be either factor IX
or a novel new substrate for TF-fVIIa. Future experiments will test these
hypotheses.
PMID- 9639046
TI - Semen donor selection by in vitro sperm mobility increases fertility and semen
storage in the turkey hen.
AB - Commercial turkey production relies on the artificial insemination (AI) of pooled
semen. However, semen quality ultimately depends on the quality of individual
ejaculates. The purpose of this study was to evaluate semen from individual toms
by means of an objective sperm-mobility assay. Semen was then pooled by mobility
phenotype and inseminated into hens, and the percentages of fertile and hatched
eggs were determined after egg incubation. To indirectly evaluate hens' sperm
storage, we determined the number of sperm holes in the perivitelline layer (PL)
of freshly laid eggs. Semen from individual ejaculates (two trials, total of 169
toms) was evaluated by use of the sperm-mobility test (SMT). Semen was diluted to
1 x 10(9) sperm/ml, in prewarmed N-tris-[hydroxymethyl] methyl-2-amino
ethanesulfonic acid (TES)-buffered saline, and was placed over 3 ml of a 2% (w/v)
Accudenz solution at 41degrees C. After a 5-minute incubation period, the cuvette
was placed in a densimeter, and percentage transmission was recorded after 1
minute. Semen samples from toms ranked, according to sperm mobility, in the
highest 10% and the lowest 10%, after three evaluations, were pooled by group and
were used to inseminate hens weekly (trial 1: n = 20 hens/group, for 10 weeks, AI
dose 150 x 10(6) spermatozoa inseminated fresh and after 24-hour in vitro storage
at 5 degrees C; trial 2: n = 60 hens/group, for 16 weeks, AI dose = 75 x 10(6)
spermatozoa inseminated fresh). Each week, eggs from day 6 post-AI were evaluated
for holes in the PL, vestiges of acrosomal induced hydrolysis. Spermatozoa from
toms of different mobility phenotypes were also evaluated individually, for sperm
chromatin structure and motility variables, by use of the Hobson Sperm Tracker.
Toms characterized by high and low in vitro sperm-mobility phenotype were
categorized as "high mobility" and "low mobility," respectively. The percentage
of fertile eggs from hens inseminated with semen from the high-mobility toms was
higher than the percentage of fertile eggs from the low-mobility group, in each
trial (95.8+/-1.3% vs. 90.4+/-2.2%, and 88.7+/-4.0% vs. 82.4+/-0.4%, trials 1 and
2, respectively; P < 0.05). More sperm holes were observed in the PL of eggs
fertilized by the high-mobility toms than in the PL of eggs fertilized by the low
mobility toms (P < 0.05). No differences in susceptibility of sperm nuclear DNA
to denature in situ, as measured by the flow-cytometric sperm chromatin-structure
assay, were detected between toms of differing mobility phenotypes. Sperm
motility variables, straight-line velocity, and average-path velocity were
significantly greater for high-mobility toms compared to low-mobility toms (P <
0.05). Sperm-mobility differences between toms (detected by means of the SMT)
influenced sperm storage, as indicated by the number of sperm in the PL and by
the percentage of fertile eggs produced.
PMID- 9639047
TI - Presence and modulation of interleukin-12 in seminal plasma of fertile and
infertile men.
AB - Interleukin-12 (IL-12) is a unique cytokine that recently has drawn considerable
attention because of its immunomodulatory properties and its possible involvement
in several normal physiological and pathophysiological processes. In the present
study, concentrations of IL-12 were determined, in the seminal plasma of fertile
(n = 33), male-factor-infertile (n = 27), and immunoinfertile (n = 14) men, to
investigate its role, if any, in male infertility. Levels of IL-12 were expressed
both as picograms per milliliter and as picograms per milligram protein. IL-12
was detected in seminal plasma of fertile men as well as in that of infertile
men. The levels of IL-12 in seminal plasma of both male-factor and
immunoinfertile men were significantly (P < 0.05) different from those of fertile
men, when levels were expressed as picograms per milligram protein. When
expressed as picograms per milliliter, the levels of IL-12 differed significantly
between the immunoinfertile group and the fertile/male-factor-infertile group.
There was significant correlation between the IL-12 levels and the total sperm
count and percentage of morphologically normal sperm in the semen, whether groups
were analyzed together or individually by condition. These findings suggest that
IL-12 may have a role in fertility and that its derangement may be involved in
male infertility.
PMID- 9639048
TI - Hormonal regulation of spermatogenesis in the hypophysectomized rat: FSH
maintenance of cellular viability during pubertal spermatogenesis.
AB - The potential for follicle-stimulating hormone (FSH) to promote germ-cell
survival and the cellular sites of FSH action were studied using a gonadally
maturing (pubertal), hypophysectomized (Hx) rat model in which residual
testosterone (T) activity was blocked by injections of an androgen-receptor
antagonist, flutamide. Recombinant human FSH was given to androgen-deprived and
androgen-blocked male rats at 27 days of age to determine maintenance of
individual germ-cell types at 35 days of age. Follicle-stimulating hormone
significantly increased testis weights and tubular diameters as compared with Hx
and Hx-flutamide controls, although testis weights in FSH-treated animals were
significantly lower than in pituitary-intact animals. Morphometric assays to
determine ratios of germ cells to Sertoli cells and to determine the number of
germ cells present per hour of development showed that the population of type A
spermatogonia in the early stages of the cycle was not responsive to FSH.
Follicle-stimulating hormone had a marked ability to maintain cell viability in
the rapid, successive divisions that begin in the latter part of the cycle and
that continue through the next cycle (i.e., from type A1 to A4 and from
intermediate spermatogonia to type B spermatogonia to preleptotene spermatocytes
to leptotene/zygotene spermatocytes to young pachytene spermatocytes). The data
also suggest T responsiveness of these cell types since the Hx-FSH-flutamide
group showed lower cell viability at the aforementioned steps when compared with
the Hx-FSH group. Too few cell types were present at subsequent phases of
spermatogenesis to allow a sensitive determination of FSH activity in the
maintenance of cell viability. The data show the potential of FSH in the absence
or relative absence of T activity to maintain cell viability. These data support
the concept of overlapping and synergistic (or additive) effects of T and FSH in
the immature rat and identify the cellular sites of FSH action.
PMID- 9639049
TI - Hormonal regulation of spermatogenesis in the hypophysectomized rat: cell
viability after hormonal replacement in adults after intermediate periods of
hypophysectomy.
AB - A quantitative analysis of germ-cell populations in normal, hypophysectomized
(Hx), and Hx-hormone-treated animals was undertaken during periods of regression
that were characterized as intermediate, between short-term and long-term
regression of the testis. Twenty-one groups of adult rats were administered
either follicle-stimulating hormone (FSH), growth hormone, thyroid-stimulating
hormone (TSH), or testosterone (T) in various doses and combinations. The dosage
of T administered was less than that expected to achieve maximum testis weight.
Flutamide and Casodex were used to compete with androgen binding to receptors in
Hx animals, as it is known that small amounts of androgen are secreted in the
absence of pituitary stimulation. Follicle-stimulating hormone, T, and TSH all
significantly maintained testis weight as compared with Hx controls, although FSH
and T, singly or in combination, were the most effective. Contamination of the
TSH preparation with trace amounts of FSH was apparently responsible for the
slight maintenance of testis weight. A novel assay for determination of the
numbers of viable germ cells was used in a subset of these groups to determine
the cellular sites of FSH and T action. Numbers of type A spermatogonia were
lowered after Hx and were maintained by either FSH or T or a combination of these
hormones. Other phases of germ-cell development most susceptible to FSH and/or T
were the successive conversions of type A spermatogonia to intermediate
spermatogonia, intermediate spermatogonia to type B spermatogonia, preleptotene
spermatocytes to pachytene spermatocytes, and early pachytene spermatocytes to
intermediate maturity pachytene spermatocytes during early and midcycle phases of
pachytene spermatocyte development. Germ-cell loss during meiosis and virtually
every phase of spermatid development was largely prevented by FSH or T or a
combination of these hormones. Thus, in testes in advanced stages of regression,
both FSH and T were capable of preventing cell loss, suggesting that both
hormones can affect the survival of the same cell type. The present study
demonstrated that FSH can partially compensate for lowered T levels. The combined
administration of FSH and T was more effective in preventing overall cell
degeneration than either hormone alone. Unlike the initial phase of
spermatogenesis, in which there is a largely midcycle loss of germ cells due to
Hx, the loss of cells during testis regression is more widespread and impacts
several cell types in more than one stage of the spermatogenic cycle.
PMID- 9639050
TI - Hormonal regulation of spermatogenesis in the hypophysectomized rat: quantitation
of germ-cell population and effect of elimination of residual testosterone after
long-term hypophysectomy.
AB - Spermatogenesis continues after long-term hypophysectomy (Hx), but massive cell
degeneration prevents seminiferous tubules from attaining the full complement of
cells. One objective of this study was to determine the vulnerable sites for
completion of spermatogenesis in long-term Hx rats. It is now known that Leydig
cells continue to secrete small amounts of androgen after Hx. A second objective
was to determine the cellular sites that are maintained by residual androgen
secreted by Leydig cells post-Hx. Two groups of adult animals were utilized. Both
groups were Hx for 36 days, but one group of rats received the androgen
antagonist flutamide during the 26th through the 36th day of Hx (10 days). Germ
cell numbers were quantified using a method that allowed their expression as
numbers of cells present per hour of development. In the long-term Hx rat, the
germ-cell population increased to preleptotene, but the divisions that led to
preleptotene were inefficient due to cell degeneration. Subsequent to
preleptotene, there was a gradual loss in cells such that there were few germ
cells remaining by steps 9-13. Flutamide given to Hx rats did not result in a
significant difference in the numbers of intermediate and type B spermatogonia or
significant differences in progenitor cells. A significant and major depression
of cell numbers in Hx-flutamide-treated rats occurred in the cell division of
type B spermatogonia to form preleptotene spermatocytes. There was a less
dramatic, although significant, depression of cell numbers in Hx-flutamide
treated animals that occurred from preleptotene until late pachytene as well as
an increased loss of round spermatids at midcycle (step 5-6). These data
demonstrate that cell loss after long-term Hx occurs at numerous phases of
spermatogenesis. The data also demonstrate that the presence of residual androgen
action after long-term Hx results in enhanced germ-cell survival. Although the
major blockage in cell viability occurs at midcycle steps in the long-term Hx
rat, there are several other hormone-sensitive phases of spermatogenesis.
PMID- 9639051
TI - Seminal vesicles are novel sites of luteinizing hormone/human chorionic
gonadotropin-receptor gene expression.
AB - The hypothesis that rat seminal vesicles may contain luteinizing hormone
(LH)/human chorionic gonadotropin (hCG) receptors was tested by means of a number
of different techniques. Northern blotting demonstrated that rat seminal vesicles
contained multiple LH/hCG-receptor transcripts. In situ hybridization revealed
that these transcripts were present primarily in the principal epithelial cells
lining the lumen. Western immunoblotting detected proteins, two of which
disappeared (80 and 46 kDa) and another of which decreased (30 kDa) after
preabsorption of the receptor antibody with excess receptor peptide. Ligand
blotting showed that 125I-hCG could bind only to an 80-kDa protein and that this
binding was inhibited by coincubation with excess unlabeled hCG.
Immunocytochemistry demonstrated that LH/hCG-receptor protein was present
primarily in the principal epithelial cells. In conclusion, our data demonstrate
that seminal vesicles contain LH/hCG receptors, thus making this previously
unsuspected male accessory reproductive organ a potential target of direct
regulation by LH.
PMID- 9639053
TI - Neuronal nitric oxide synthase in the canine prostate: aging, sex steroid, and
pathology correlations.
AB - Nitric oxide synthase (NOS) is expressed in the prostate of various species,
including humans. NOS catalyzes the production of nitric oxide (NO), which may
function in prostatic smooth-muscle relaxation. To investigate further the role
of NO in the prostate, we examined neuronal NOS expression in the aging canine
prostate, after hormonal perturbation, and correlated these results with
histopathologic findings. The study comprised the following treatment groups:
intact dogs (treatment group 1, n = 6); dogs who were castrated at 7 days of age
and received testosterone and estrogen replacement at 2 years of age (treatment
group 2, n = 10); and dogs who were castrated at 2 years of age and received
testosterone and estrogen replacement at 2 years of age (treatment group 3, n =
9). Studies were done on prostates removed from dogs after euthanasia at 6 years
of age. In treatment group 1, complex benign prostatic hyperplasia (BPH) was
observed in all specimens. In treatment group 2, atrophy was observed in 70%,
normal prostate with small areas of hyperplasia in 20%, and BPH in 10% of
specimens. In treatment group 3, atrophy was observed in 78%, normal histology
with small areas of hyperplasia in 11%, and BPH in 11% of specimens. Neuronal NOS
localizations were confirmed by western blot analysis and by immunohistochemistry
in 0% and 17%, respectively, of specimens in treatment group 1, in 60% and 70%,
respectively, of specimens in treatment group 2, and in 67% and 71%,
respectively, of specimens in treatment group 3. Neuronal NOS immunoreactivity
was localized in histologically normal prostates of four intact, young-adult
control dogs (2 years of age). For all treatment groups, neuronal NOS
immunoreactivity was confirmed by western blot in 86% of atrophic prostates but
in no prostates with BPH (P < 0.001), and it was confirmed by
immunohistochemistry in 75% of atrophic prostates but in only 13% of prostates
with BPH (P < 0.02). These data suggest that, in the canine prostate, NO release
relates to growth and pathology. Low levels of neuronal NOS expression in BPH
tissue, compared with higher levels in atrophic tissue, suggest that neuronal NOS
expression is down-regulated in the prostate with benign cellular proliferation
whereas it is maintained or possibly up-regulated in the prostate with prostatic
involution. Whether altered neuronal NOS expression contributes to the
pathogeneses of BPH and prostatic involution or whether it occurs as a
consequence of these processes requires further investigation.
PMID- 9639052
TI - Ethnic differences in testicular structure and spermatogenic potential may
predispose testes of Asian men to a heightened sensitivity to steroidal
contraceptives.
AB - Spermatogenesis in Asian men appears to be more susceptible to suppression by
steroidal contraceptives administered in clinical trials than spermatogenesis in
Caucasian men. The objective of this study was to determine whether ethnic
differences exist in testicular structure and spermatogenic potential that might
predispose Asians to a high sensitivity to steroidal contraceptives. Testes from
12 Chinese men were compared to those from 8 Hispanic men and 12 non-Hispanic
Caucasian men of ages 29+/-3, 30+/-2, and 29+/-3 years, respectively. Testes were
fixed by vascular perfusion with glutaraldehyde, further fixed in osmium,
embedded in Epon, and evaluated by stereology using 0.5-microm sections stained
with toluidine blue. Homogenates of fixed testes were evaluated for the number of
Sertoli cells and the daily sperm production based on pachytene primary
spermatocytes (PDSP) or spermatids with spherical nuclei (DSP). Paired
parenchymal weight was less (P < 0.05) in Chinese men than in Hispanic or
Caucasian men. The PDSP per gram of parenchyma was lower (P < 0.05) and the DSP
per gram tended to be lower in Chinese men than in other groups. The histologic
appearance, volume density, and length per man of seminiferous tubules were the
same among the ethnic groups; however, the diameter of seminiferous tubules was
less (P < 0.05) in Chinese than in Hispanic or Caucasian men. The PDSP per man
and the DSP per man were lower (P < 0.05) in Chinese than in Hispanic or
Caucasian men. The number of Sertoli cells per gram was higher (P < 0.05) in
Chinese or Caucasian men than in Hispanic men, but the number of Sertoli cells
per man was lower (P < 0.05) in Chinese men than in Hispanic or Caucasian men.
Sertoli cell function, measured as the number of germ cells accommodated by a
single Sertoli cell, was lower (P < 0.05) in Chinese men than in Caucasian men.
The volume density of Leydig cell cytoplasm was greatest (P < 0.05) in Chinese
men, but the number of Leydig cells was similar among the ethnic groups. Hence,
smaller testes coupled with reduced Sertoli cell number and function and reduced
daily sperm production could predispose Asian men to have a heightened negative
response of testes to steroidal contraceptives, as compared to Caucasian men.
Dampening (by exogenous androgens) of any physiological benefit to
spermatogenesis that a high volume density of Leydig cell cytoplasm may bestow on
the human testis (that Asian men may have evolved to require) would exacerbate
ethnic differences in the spermatogenic response to hormonal contraceptives.
PMID- 9639054
TI - Expression of 140-kDa neural cell adhesion molecule in developing testes in vivo
and in long-term Sertoli cell-gonocyte cocultures.
AB - The basis for cell-cell adhesion in the seminiferous epithelium of the developing
testis is doubtless critical in supporting events that are essential for the
onset and maintenance of normal spermatogenesis. In this study, we applied
immunoblotting and immunolocalization approaches for the following reasons: 1) to
ask whether neural cell adhesion molecule (NCAM) underlies cell-cell interactions
in vivo, as we previously showed for cells in vitro, 2) to characterize the
isoform or isoforms of NCAM expressed during testicular development, and 3) to
study NCAM expression in long-term Sertoli cell-gonocyte cocultures and to
compare and contrast this pattern of expression with that in vivo. Our findings
indicate that NCAM is found ubiquitously at cell-cell interfaces within the
seminiferous cord from birth through day 10 and thereafter is restricted to
interstitial cells. Moreover, only polysialic acid-negative 140-kDa NCAM is
expressed in the testis or in coculture, an isoform whose properties are
compatible with the concept of NCAM as both a direct modifier of cell function
and an indirect influence on cell responses mediated by other external factors.
In addition, we found that germ cells, potentially gonocytes or Type A
spermatogonia, persist in long-term cocultures maintained for 15 days after
isolation from 5-day-old rat pups and that NCAM continues to be expressed at high
levels in these cultures. This observation is in marked contrast to our
observation that NCAM gradually decreases and eventually disappears in vivo by
postnatal day 15. Thus, our findings indicate that 140-kDa NCAM is prominent in
neonatal testes but is down-regulated by as yet unidentified mechanisms
thereafter. Our findings also indicate that down-regulation of NCAM fails to
occur in hormone- and serum-free Sertoli cell-germ cell cocultures.
PMID- 9639055
TI - Glutamate transport and storage in synaptic vesicles.
AB - Glutamate plays an important metabolic role in virtually every vertebrate cell.
In particular, glutamate is the most common excitatory neurotransmitter in the
vertebrate central nervous system. As such, the mechanism by which glutamate is
diverted from its normal metabolic activities toward its role as a
neurotransmitter has, in recent years, been systematically investigated. In
glutamatergic nerve endings, synaptic vesicles accumulate and store a proportion
of the cellular glutamate pool and, in response to appropriate signals, release
glutamate into the synaptic cleft by exocytosis. Glutamate accumulation is
accomplished by virtue of a glutamate uptake system present in the synaptic
vesicle membrane. The uptake system consists of a transport protein, remarkably
specific for glutamate, and a vacuolar-type H+-ATPase, which provides the
coupling between ATP hydrolysis and glutamate transport. The precise manner in
which the glutamate transporter and H+-ATPase operate is currently the subject of
debate. Recent data relevant to this debate are reviewed in this article.
Additionally, pharmacological agents thought to specifically interact with the
vesicular glutamate transporter are discussed. Finally, a newly discovered,
endogenous inhibitor of vesicular uptake, inhibitory protein factor (IPF), is
discussed with some speculations as to its potential role as a presynaptic
modulator of neurotransmission.
PMID- 9639056
TI - Pathophysiological effects of dietary essential fatty acid balance on neural
systems.
AB - Dietary fatty acid balance has been revealed to affect neural functions as well
as chronic diseases such as cancer, cerebro- and cardiovascular diseases, and
allergic hyper-reactivity. In this review, we focused on the pathophysiological
effects of n-6 and n-3 fatty acids on brain functions. Long-term n-3 fatty acid
deficiency in the presence of n-6 fatty acids has been shown to affect learning
behavior, drug sensitivity and retinal functions. Some membrane enzymes and ion
channel functions have been shown in experimental animals to be regulated by
membrane fatty acid modifications. We also summarized the effects of these fatty
acids in diets on human psychotic aspects and brain diseases. Although
biochemical mechanisms remain to be elucidated, investigations on the effect of
dietary fatty acids on neural networks may provide an important clue to clarify
complex brain functions.
PMID- 9639057
TI - Stimulatory guanine nucleotide-binding protein in failing heart of hamsters and
rats.
AB - The role of the stimulatory guanine nucleotide-binding protein (Gs) in heart
failure is unclear. We therefore determined the amount of protein and mRNA of Gs
in the failing myocardium using two animal models: the BIO 53.58 hamster, a model
of genetic cardiomyopathy, and adriamycin-treated rats (ADR rats), a model of
secondary cardiomyopathy. The maximal number of myocardial beta-adrenoceptors in
the BIO 53.58 hamsters as well as in the ADR rats was significantly lower than
that in the respective controls, indicating that the beta-adrenoceptors were down
regulated in heart failure. Analysis by Western blot and Northern blot revealed a
significant decrease in Gs protein and mRNA in the BIO 53.58 hamsters relative to
the control. There were no differences in the level of Gs protein or mRNA in the
ADR rats vs the controls. The functional activity of Gs was investigated by
measuring adenylate cyclase activity. The activity of adenylate cyclase in
response to stimulation by sodium fluoride or forskolin was decreased in the BIO
53.58 hamsters relative to control animals, whereas no differences were observed
in the ADR rats vs the controls. Thus, alterations in Gs in the failing heart
appear to differ according to its cause.
PMID- 9639058
TI - Protective effects of ranolazine, a novel anti-ischemic drug, on the hydrogen
peroxide-induced derangements in isolated, perfused rat heart: comparison with
dichloroacetate.
AB - The effect of ranolazine, a novel anti-ischemic drug that stimulates the activity
of pyruvate dehydrogenase, on hydrogen peroxide (H2O2)-induced mechanical and
metabolic derangements was studied in isolated rat heart and compared with that
of dichloroacetate (DCA), an activator of pyruvate dehydrogenase. The heart was
perfused aerobically by the Langendorff's technique at a constant flow and driven
electrically. H2O2 (600 microM) decreased the left ventricular developed pressure
and increased the left ventricular end-diastolic pressure (i.e., mechanical
dysfunction), decreased the tissue level of adenosine triphosphate (i.e.,
metabolic derangement), and increased the tissue level of malondialdehyde (MDA)
(i.e., lipid peroxidation). These mechanical and metabolic derangements induced
by H2O2 were significantly attenuated by ranolazine (10 or 20 microM). On the
other hand, DCA (1 mM) was ineffective in attenuating the H2O2-induced mechanical
and metabolic derangements. Ranolazine, however, did not modify the tissue MDA
level, which was increased by H2O2. In the normal (H2O2-untreated) heart,
ranolazine did not alter the mechanical function and energy metabolism. These
results demonstrate that ranolazine attenuates mechanical and metabolic
derangements induced by H2O2. It is suggested that the protective action of
ranolazine against the H2O2-induced derangements is due to neither the energy
sparing, DCA-like, nor anti-oxidant effects.
PMID- 9639059
TI - Comparison of atypical beta3-adrenoceptor agonists with their respective
metabolic activities in rat white adipocytes.
AB - The metabolic activities of four types of beta3-adrenoceptor (AR) agonists,
BRL35135A, BRL28410, ICI215001 and CL316243, were compared with those of other
beta1- and beta2-AR agonists in rat white adipocytes. All the beta3-AR agonists
caused cAMP formation, free fatty acid release and 2-deoxyglucose uptake; the
maximum activity levels were similar except for ICI215001, which was lower.
However, the magnitude of potency and selectivity of these agonists differed. The
most potent and selective beta3-agonist was CL316243. Metabolic activities and
Northern blotting showed that there were three beta-AR subtypes that were coupled
to adenylyl cyclase and contributed to the induction of lipolysis and glucose
uptake. The rank order of the amounts of beta-AR subtypes was beta3 >>beta1>
beta2. However, the physiological functions of beta-AR subtypes were essentially
similar in rat white adipocytes. On the other hand, cAMP accumulation and
Northern blotting showed that human adipocytes predominantly contained beta2-AR,
with far lower levels of beta1- and beta3-ARs. These findings suggested that the
beta3-AR plays an important role in energy metabolism and thermogenesis in which
cross talk exists between beta1- and beta3-ARs in rat adipocytes, while beta2-AR
is the most important for the lipolysis regulation in human subcutaneous
adipocytes.
PMID- 9639060
TI - Affinity of mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors
in guinea pig ileum.
AB - We examined the binding affinity of mosapride citrate (mosapride) (4-amino-5
chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl] benzamide citrate),
a novel gastroprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in
guinea pig ileum using a selective 5-HT4-receptor radioligand, [3H]GR113808. In
membrane preparations from longitudinal muscle with myenteric plexus in guinea
pig ileum, specific [3H]GR113808 binding revealed a single saturable site of high
affinity (Kd=0.28 +/-0.02 nM, Bmax = 45+/- 3 fmol/mg protein). Mosapride and
other 5-HT4-receptor agonists inhibited the specific binding of [3H]GR113808 in
guinea pig ileum. The 5-HT4 agonists examined displayed the following inhibition
potency order: BIMU-8 > cisapride > mosapride > renzapride > 5-HT > zacopride >
metoclopramide. Mosapride exhibited monophasic inhibition of the specific
[3H]GR113808 binding in the ileum (Ki value: 84.2 nM). The presence of mosapride
(30 nM) significantly increased the Kd value to 0.44+/-0.05 nM in the Scatchard
analysis of [3H]GR113808 binding. Bmax of [3H]GR113808, however, was not affected
(48 +/-4 fmol/mg protein) by mosapride. As for the affinity of mosapride, the
addition of GppNHp (100microM) slightly increased the Ki value to 104 nM. These
results indicate that mosapride has an affinity for 5-HT4 receptors in guinea pig
ileum in the radioligand binding study.
PMID- 9639061
TI - Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced
orthostatic hypotension.
AB - Newly developed alpha1-adrenoceptor antagonists including naftopidil are free
from the "prazosin-like" side effect of orthostatic hypotension and associated
symptoms. We investigated the mechanism for the differential effects of
naftopidil and prazosin on the development of postural hypotension, with special
attention on their selectivity for the alpha1-adrenoceptor subtype. We observed
that head-up tilt caused a similar extent of drop in mean arterial pressure in
control, naftopidil (1 mg/kg)- or prazosin (10 microg/kg)-treated rats; however,
the tilt-induced postural hypotension was recovered within 2 min in the
naftopidil-treated group, but not in the prazosin-treated group. Comparing an
inhibitory effect on noradrenaline-induced contraction in the rat aorta and
portal vein, we found that naftopidil was sixfold less potent in the portal vein,
while prazosin showed similar potency in both tissues. Reverse transcription
polymerase chain reaction analysis showed that the expression of alpha1d
adrenoceptor mRNA predominated in the aorta, while that of alpha1b-adrenoceptor
mRNA predominated in the portal vein. Using cloned rat alpha1-adrenoceptor
subtypes, we found that naftopidil was selective for the alpha1d-subtype with
approximately ninefold higher affinity than at the other subtypes. These results
show that the pharmacological character of naftopidil, combined with the
differential expression of the alpha1-adrenoceptor subtype in the artery and the
vein, may partly explain the differential effect of naftopidil and prazosin on
head-up tilt-induced hemodynamic responses.
PMID- 9639062
TI - Effects of SS320A, a new cysteine derivative, on the change in the number of
goblet cells induced by isoproterenol in rat tracheal epithelium.
AB - We examined the effects of SS320A ((-)-(R)-2-amino-3-(3
hydroxypropylthio)propionic acid), a new cysteine derivative, on the change in
the number of goblet cells induced by isoproterenol in rat tracheal epithelium.
Four types of goblet cells were characterized in tracheal epithelium according to
their size and staining affinity with Alcian blue (AB) / periodic acid Schiff
(PAS). When each rat was given a single daily injection of isoproterenol (0.05
mg/kg, i.p.) for 14 days, a significant increase was observed in AB/PAS-positive
cells that were recognizable as goblet cells in tracheal epithelium. When SS320A
(10-100 mg/kg, p.o.) or propranolol (1 mg/kg, s.c.) was administered before each
injection of isoproterenol, the increase in the number of goblet cells induced by
isoproterenol was significantly inhibited. There was no difference between male
and female rats with regard to this inhibitory action. On the other hand,
ambroxol, bromhexine, L-cysteine ethyl ester and S-carboxymethylcysteine (100
mg/kg, p.o., respectively), which are used as expectorants, had no inhibitory
effects on the isoproterenol-induced change in the number of goblet cells. Four
metabolites (M1-M4) of SS320A in rats also failed to inhibit the change induced
by isoproterenol. These data suggest that SS320A itself may have a beneficial
effect against mucus hypersecretion in chronic respiratory diseases.
PMID- 9639063
TI - Cardioprotective effects of an angiotensin-converting-enzyme inhibitor,
imidapril, and Ca2+ channel antagonist, amlodipine, in spontaneously hypertensive
rats at established stage of hypertension.
AB - The present study was performed to compare cardioprotective effects of an
angiotensin-converting-enzyme inhibitor, imidapril, and of a Ca2+ channel
antagonist, amlodipine, against the cardiac hypertrophy in male spontaneously
hypertensive rats (SHRs) at the established stage of hypertension. Fifteen-week
old SHRs were given imidapril (2 and 5 mg/kg/day) or amlodipine (10 mg/kg/day) by
gavage for 8 weeks. Three hours after the 1st treatment, imidapril moderately
reduced blood pressure without changing heart rate, while amlodipine caused a
marked reduction in blood pressure accompanied by transient tachycardia. At the
end of the treatments, ventricular weight in the imidapril-treated groups was
markedly lower, but that in the amlodipine-treated group was only slightly lower
than that in the vehicle-treated group. Myocardial collagen content in the
imidapril-treated group tended to be decreased, and significant reduction was
observed in the low-dose group. In another experiment, the isolated heart of the
imidapril-treated animals demonstrated better cardiac compliance than that in the
vehicle-treated animals. In contrast, amlodipine failed to improve cardiac
function. The present results suggest that imidapril possesses advantageous
effects to prevent cardiac hypertrophy and deteriorated cardiac function in SHRs
of established stage of hypertension as compared with amlodipine.
PMID- 9639064
TI - Difference in inhibitory effects of dexamethasone and cyclosporin A on Sephadex
bead-induced airway hyperresponsiveness and inflammation in rats.
AB - We investigated the effects of dexamethasone and cyclosporin A on Sephadex bead
(Sephadex G-200, Sephadex)-induced airway hyperresponsiveness (AHR) and
inflammation in rats. Sephadex (0.5 mg/animal) was intravenously administered on
days 0, 2 and 5. Bronchoalveolar lavage, histological study and measurement of
AHR were performed on day 7. Dexamethasone (0.1, 1 and 10 mg/kg, p.o. x 3) and
cyclosporin A (0.1, 1 and 10 mg/kg, s.c. x 3) clearly inhibited the increase in
eosinophils in bronchoalveolar lavage fluid after Sephadex injection. On
histological study, pulmonary eosinophilia, granulomatous arteritis with
horseshoe-shaped multinuclear giant cell formation and goblet hyperplasia were
observed after Sephadex injection. Both dexamethasone (10 mg/kg x 3) and
cyclosporin A (10 mg/kg x 3) inhibited these findings and an increase in
eosinophil peroxidase in the lung. Dexamethasone dose-dependently inhibited AHR
induced by Sephadex, and completely suppressed it at a dose of 1 mg/kg (x 3).
Cyclosporin A, however, did not inhibit AHR even at a dose of 10 mg/kg ( x 3).
These results show that there is a difference between dexamethasone and
cyclosporin A in the inhibitory effect on Sephadex-induced AHR, and they suggest
that eosinophils are not directly associated with the development of AHR after
Sephadex injection.
PMID- 9639065
TI - Coronary artery diameter increase induced by a phosphodiesterase 5 inhibitor,
E4021, in conscious pigs.
AB - The effects of intravenous infusions of 1, 3 and 10 microg/kg/min of the
phosphodiesterase 5 inhibitor, E4021, at 30-min intervals on coronary artery
diameter were studied in 8 conscious pigs monitored with a pair of piezoelectric
crystals. The highest dose increased the diameter by 2.9 +/-0.5% (P <0.01 vs
vehicle) of the baseline diameter, with a significant decrease in mean pulmonary
arterial pressure. However, there were no changes in mean aortic pressure and
heart rate. Additionally, E4021 significantly prolonged the duration of the
diameter increase induced by nitroglycerin. Thus, phosphodiesterase 5 inhibition
causes coronary artery diameter increase and produces an amplifying effect with
nitroglycerin.
PMID- 9639066
TI - Inhibition by [Arg8]-vasopressin of long term potentiation in guinea pig
hippocampal slice.
AB - We examined the effects of [Arg8]-vasopressin (AVP) on long term potentiation
(LTP) of the field excitatory postsynaptic potentials at CA1 and CA3 synapses in
adult guinea pig hippocampal slices. AVP (10 nM) depressed the magnitude of LTP
without any effects on basal responses at both synaptic pathways. The depressive
effect by AVP at CA1 synapses appears to be receptor-mediated since it was
inhibited by an AVP V1-receptor antagonist, [Pmp1,Tyr(Me)2]-AVP. From these
results, AVP may play an inhibitory role on the induction of LTP via V1 receptors
in the guinea pig hippocampus.
PMID- 9639067
TI - HIV and HIV dementia.
PMID- 9639068
TI - SIV infection of macaques--modeling the progression to AIDS dementia.
AB - AIDS dementia complex affects 15-20% of HIV-infected adults and a greater
percentage of HIV-infected children. Whether or not an HIV-infected individual
develops neurological disease and how early in infection the clinical signs
appear is most likely the net result of both viral virulence factors and host
factors. Important viral factors include cell tropism and sequences that
determine neurovirulence. The host factors include the cellular expression of
viral co-receptors and maintenance of competent immune responses. The
pathogenesis of AIDS dementia complex is difficult to study in the human host
because of the difficulty in identifying acutely infected individuals and the
inaccessibility of human brain tissue for examination during infection. The
SIV/macaque model is excellent for the study of viral virulence factors and host
responses to infection. This review outlines how the SIV/macaque model has been
used to identify viral factors that are important for the development of
neurological disease, to determine when HIV enters the brain, and to characterize
the host immune responses affecting virus entry to the CNS and the development of
neurological disease.
PMID- 9639069
TI - Simian immunodeficiency virus encephalitis in rhesus macaques is associated with
rapid disease progression.
AB - Central nervous system (CNS) disease is a major feature of simian
immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS
lesions in SIV-infected macaques and the potential associations with viral strain
and disease course, we performed a retrospective analysis of necropsies on 124
macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed
in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion
occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all
animals. The incidence of SIVE correlated significantly with shortened survival
(P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors
(animals that died within 200 days) compared to only 18% (16/89) of normal
progressors (animals that lived longer than 200 days) (P=0.011). Animals with
SIVE had higher viral loads in peripheral blood than those that did not, but this
difference did not reach statistical significance. Similarly, while animals
infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51)
than animals infected with molecularly cloned SIVmac239 and its T-cell tropic
derivatives (18.5%; 10/54) this difference was not statistically significant. In
this study rapid disease progression and SIVE were highly correlated making
separation of viral determinants of virulence from those of neurovirulence
difficult.
PMID- 9639070
TI - Efficient infection of brain microvascular endothelial cells by an in vivo
selected neuroinvasive SIVmac variant.
AB - A neuroinvasive/neuropathogenic SIV variant termed SIVmac182 was previously
isolated and characterized (Watry et al, 1994). This neuroinvasive strain was
derived from the uncloned strain SIVmac251 through serial animal passage of
infected microglia, unlike previously reported neurovirulent strains.
Importantly, the virus described here was isolated from a strain which already
demonstrates limited neuroinvasiveness in vivo, through a route of inoculation
which exerts selective pressure for variants in the periphery that can naturally
cross the blood-brain barrier and gain access to the brain. Examination of animal
tissues indicated that the neuroinvasive strain was capable of replicating in
brain microvascular endothelial cells (BMEC). Therefore, we developed an in vitro
model of BMEC infection in which to examine mechanisms of virus neuroinvasiveness
and neuropathogenicity as well as to address mechanisms of HIV-induced dementia.
Results obtained with this in vitro system indicate that growth in BMEC may
predict neuroinvasiveness in vivo, and furthermore, that brain passage of virus
results in the generation of neuroinvasive strains which demonstrate an increased
efficiency of BMEC infection in vitro.
PMID- 9639071
TI - Neuronal apoptosis induced by HIV-1 Tat protein and TNF-alpha: potentiation of
neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia.
AB - Apoptosis of neurons and non-neuronal cells has been demonstrated in the brain of
AIDS patients with dementia. Previous studies suggest that the apoptotic stimuli
are likely to be soluble factors. Several candidates for the soluble factors that
lead to neuronal apoptosis in HIV-1 infection have been proposed, including the
HIV-1 Tat protein and TNF-alpha. The mechanisms that lead to neuronal apoptosis
in the brain of AIDS patients in vivo, may involve the combined effects of more
than one pro-apoptotic factor. In this study, we examine whether exposure of
primary human neurons to the combination of HIV-1 Tat and TNF-alpha can
potentiate the induction of neuronal apoptosis compared with exposure to either
factor alone. TNF-alpha was shown to potentiate the induction of neuronal
apoptosis by HIV-1 Tat via a mechanism that involves increased oxidative stress.
Antioxidants inhibited, but did not completely abolish the induction of neuronal
apoptosis by Tat, suggesting that other mechanisms are also likely to be
involved. These findings suggest that soluble HIV-1 Tat and TNF-alpha may play a
role in neuronal apoptosis induced by HIV-1 infection of the CNS, particularly
when present in combination. Our findings further suggest that one mechanism
whereby combinations of pro-apoptotic factors may potentiate the induction of
neuronal apoptosis in the brain of AIDS patients is by increasing oxidative
stress. Understanding the role of oxidative stress and other mechanisms that lead
to apoptosis in HIV-1 infection of the CNS may advance the development of new
therapeutic strategies to prevent neuronal cell death and improve neurologic
function in AIDS patients.
PMID- 9639072
TI - Anomalies in Nef expression within the central nervous system of HIV-1 positive
individuals/AIDS patients with or without AIDS dementia complex.
AB - In determining levels of expression of HIV-1 Nef protein within the central
nervous system (CNS) we assessed antibody responses to the protein both
peripherally and in CNS. Antibodies to Nef were not detected within the CNS
despite detection of antibodies to both gp41 and Nef in peripheral blood and
representative virus isolates derived from CNS and peripheral blood (PB) samples
containing full length nef sequence and virus-infected cells expressing Nef
protein. We conclude from this that expression of Nef within the CNS is such that
little or no antibody production occurs and that these differences indicate that
Nef protein may not be directly contributing to the AIDS dementia complex.
Expression of Nef protein in PHA-activated peripheral blood mononuclear cells
from CNS derived isolates was different to that of coincidental PB derived
isolates in that partial surface expression was observed for the latter. The
results suggest that antigenic presentation of Nef within the CNS is anomalous
and that Nef protein expression, at least for the limited number of in vitro
derived isolates tested, has a different localization pattern.
PMID- 9639073
TI - Chemokine receptors in the human brain and their relationship to HIV infection.
AB - Chemokine receptors have been recently identified as the important co-factors
which in conjunction with CD4, mediate entry of HIV into its target cells. The
brain is one of the most prominent targets of HIV infection, where it leads to
HIV encephalitis (HIVE) and HIV-associated dementia. Knowledge of the
distribution, physiology, and pathology of chemokines and chemokine receptors in
the human brain is fundamental for understanding the pathogenesis of the
interaction between HIV and the central nervous system (CNS). There is also
increasing evidence that chemokine receptors expression in the CNS increases
during pathological, especially inflammatory, conditions. The major co-factors
for HIV infection, CCR5, CCR3, and CXCR4 have been detected in the human brain in
a variety of cell types including microglia, astrocytes, neurons, and vascular
endothelial cells. Furthermore, antibodies to chemokine receptors can also block
HIV infectivity in cultured CNS cells. This indicates that chemokine receptors
are likely to have a functional role in the pathogenesis of HIVE.
PMID- 9639074
TI - Sp1 and related factors fail to interact with the NF-kappaB-proximal G/C box in
the LTR of a replication competent, brain-derived strain of HIV-1 (YU-2).
AB - The HIV-1 LTR promoter proximal G/C box array has been demonstrated to function
by interacting with the Sp1 transcription factor family whose members can act as
either activators or repressors of transcription. In this regard, we have
examined the interaction of the HIV-1 Sp binding sites with nuclear factors that
are present in cell types that support HIV-1 replication, including those of
lymphocytic, monocytic, and astrocytic origin. As determined by electrophoretic
mobility shift (EMS) competition analyses using oligonucleotides containing the
sequences of each of the Sp1 sites of HIV-1 strain LAI, the NF-kappaB-proximal Sp
site (site III) displayed the highest binding activity compared to sites I and II
with regard to Sp1 and related factors present in lymphocytic (Jurkat) and
astrocytic (U-373 MG) nuclear extracts. Sp1 and two Sp3 isoforms were detected as
the primary cellular constituents of DNA-protein complexes formed with the NF
kappaB-proximal site. Only modest differences in Sp1:Sp3 binding ratios were
observed when this site was reacted with either astrocytic or lymphocytic nuclear
extract. However, when nuclear extracts derived from two monocytic cell types
that differ in the degree of differentiation were reacted with the HIV-1 LAI Sp
site III, a large difference in Sp1 and Sp3 binding was observed. To determine if
naturally occurring and replication-competent strains of HIV-1 contain base pair
alterations within the Sp elements that affect the ability of the site to
interact with Sp1 and related factors, a series of Sp site III variants were
constructed and examined by EMS analyses. One of these sites, obtained from the
published sequence of the YU-2 strain (a brain-derived macrophage tropic strain
of HIV-1), displayed almost no Sp1 or Sp3 binding activity as a result of a
single base pair alteration in Sp site III. This base-pair alteration, when
placed in the context of an HIV-1 LAI LTR-luciferase construct, resulted in a 40
50% reduction in LTR activity in transiently transfected Jurkat and U-373 MG
cells. Overall, these results suggest that specific G/C box sequence alterations
present in the brain-derived HIV-1 variant YU-2, or possibly other brain-derived
variants, may exhibit altered replication properties as a result of the low
affinity of the NF-kappaB-proximal G/C box for members of the Sp transcription
factor family.
PMID- 9639075
TI - Survival prolongation in HIV-associated progressive multifocal
leukoencephalopathy treated with alpha-interferon: an observational study.
AB - A retrospective chart review was conducted to determine the effect of alpha
Interferon (alpha-IFN) on disease progression, symptom palliation, and survival
in HIV-associated Progressive Multifocal Leukoencephalopathy (PML). METHODS:
Subjects were HIV seropositive patients diagnosed with PML at the Johns Hopkins
Hospital between 1985 and July of 1986. Diagnostic criteria for PML included both
clinical symptomatology and histologic or radiographic confirmation. All patients
with concomitant CNS infections were excluded. Patients receiving a minimum
treatment of 3 weeks of 3 million units of alpha-IFN daily were compared to
untreated historical controls. From 104 PML cases reviewed, 77 met the defined
criteria for PML. Twenty-one patients had received open-label alpha-IFN treatment
in a non-randomized manner for at least 3 weeks, and 32 met criteria for
inclusion in the untreated group as historical controls. Deceased treated
patients were comparable to deceased untreated patients with respect to age,
gender, race, HIV risk factors, AIDS-defining illnesses, and CD4+ counts. CD4+
counts and use of anti-retroviral medications within 6 months of PML onset were
higher among those who were living at the time of the study. RESULTS: Among
deceased patients, median survival of treated patients was 127.5 days longer than
that of untreated patients (Chi-square=4.21, P=0.04). When living and deceased
treated patients were combined, the median survival was 325 days (range 35 -
1634) versus 121 days (range 46 - 176) in untreated patients (Chi-square=13.47, P
< 0.001). When survival times in untreated patients were left-censored to account
for possible survivorship bias in treated patients, survival in treated patients
remained significantly prolonged (325 days versus 175.5 days, Chi-square=4.65,
P=0.03). In addition, use of alpha-IFN was associated with a significant delay in
the onset of memory loss (Chi-square=8.59, P < 0.01). Seven alpha-IFN treated
patients showed sustained remissions of several months to over a year, with
documented improvements in mental status, aphasia, dysarthria, dysphagia,
paresis, and dyscoordination. Moreover, four IFN-treated patients had evidence of
MRI lesion regression, although this was not always correlated with clinical
remission. Four of 32 untreated patients also reported transient symptomatic
improvements. CONCLUSION: This open-label study suggests that alpha-IFN may delay
progression, palliate symptoms, and significantly prolong survival in HIV
associated PML, and we therefore suggest that a controlled clinical trial is
warranted.
PMID- 9639076
TI - Short-term side effects of stimulant medication are increased in preschool
children with attention-deficit/hyperactivity disorder: a double-blind placebo
controlled study.
AB - Preschool children with attention-deficit/hyperactivity disorder (ADHD) (27 boys,
5 girls, mean age 4 years 10 months) participated in a double-blind placebo
controlled crossover drug study to assess the side effects of methylphenidate.
Children received twice daily, for at least 1 week each, placebo, 0.3 mg/kg
methylphenidate, and 0.5 mg/kg methylphenidate. Side effects were monitored by a
parent rating scale designed for medication studies. In general, methylphenidate
was tolerated relatively well, with no children withdrawing because of adverse
effects. Of 17 childhood behaviors usually associated with side effects, 8
behaviors showed significant changes, generally at the higher dose of
methylphenidate. Interestingly, 3 of the side effects were associated with
improved behavior. The number of side effects appeared higher than what is
usually reported in a population of school-age children, but few parents reported
them as being severe. Severe side effects were reported in less than 10% of the
sample, with approximately as many reports of severe effects on placebo as on low
and high doses of the medication. The results indicate that methylphenidate has a
relatively low toxicity in preschool children (over the first 7-10 days), that
some behavioral changes that might be viewed as side effects of methylphenidate
are actually normal behaviors or ADHD behaviors in preschool children (e.g.,
sociability), that these "side-effect" behaviors are more common in preschool
than school-age children, that some "side effects" of methylphenidate are
associated with improvements in behavior, and that preschool and school-age
children may have different side effects of methylphenidate (e.g., mood changes
and anxiety).
PMID- 9639077
TI - Prevalence and patterns of psychotropic and anticonvulsant medication use in
children and adolescents referred to residential treatment.
AB - The prevalence and patterns of use of psychiatric and anticonvulsant medications
were studied in 83 seriously emotionally disturbed children and adolescents at
the time of their admission to a residential treatment facility. Youths (aged 5
19, mean = 13.6 years), consecutively admitted over 17 months, were assessed for
the prevalence and patterns of use of psychotropic and anticonvulsant treatments.
At admission, 76% of the youths were receiving psychiatric pharmacotherapy, 40%
with more than one psychiatric agent, and 15% with a combination of psychotropic
and anticonvulsant medications. Frequently prescribed medications were
neuroleptics (35 % of the medicated youths), sedative-hypnotics (26 %), and
anticonvulsants (15%). Psychostimulants (16%) and antidepressants (22%) were
under-prescribed relative to their diagnostic indications. Over 50 different
medication combinations were used. The neuroleptic + lithium combination was most
common (25 % of the polypharmacological treatments). Neuroleptics were the most
commonly prescribed medication and mostly used for nonpsychotic, nontic, and
nonbipolar indications (55% of neuroleptic trials). Neuroleptics were used
primarily for aggression regardless of diagnosis. Neuroleptics were used more in
symptomatic treatments than in treatments for indicated diagnoses. The high
prevalence of psychiatric and antiepileptic medication use in children and
adolescents admitted to a residential treatment facility, and especially the
pattern of their use, raises questions about prescribing practices for youths
entering residential treatment and about pediatric psychopharmacotherapy in
general.
PMID- 9639078
TI - Effectiveness of methylphenidate in Native American children with fetal alcohol
syndrome and attention deficit/hyperactivity disorder: a controlled pilot study.
AB - This pilot study was designed to assess the short-term effectiveness and side
effects of methylphenidate in treating symptoms of attention deficit
hyperactivity disorder (ADHD) in Native American children (5 to 12 years old)
with documented fetal alcohol syndrome (FAS) or partial fetal alcohol syndrome.
Using strict criteria for the diagnosis of FAS and ADHD, a randomized double
blind cross-over study of two placebos and a fixed dose of methylphenidate was
completed in 4 Native American children in a residential school. Each treatment
condition lasted 5 days, and daily observational outcome measures, the Conners
Parent Rating Scale (CPRS-48), and the Conners Teacher Rating Scale (CTRS-39),
were employed. Methylphenidate significantly improved scores of the Hyperactivity
Index Scale on the CPRS-48 and the CTRS-39 but not the Daydreaming-Attention
score on the CTRS-39. Side effects were similar to those traditionally found in
other populations. The promising preliminary results suggest that a more
definitive study of methylphenidate in Native and non-Native children with FAS
and ADHD is warranted.
PMID- 9639079
TI - Risperidone for young children with mood disorders and aggressive behavior.
AB - Open clinical treatment with risperidone was administered to a clinically
heterogeneous group of 11 children and adolescents (age range 5.5-16 years, mean
9.8 years) with concurrent presentation of affective symptoms (mostly suggestive
of bipolar disorder), aggressive and violent behavior, and marked management
problems. These patients had responded inadequately to several mood-stabilizing
medications. In this outpatient sample, 8 of 11 children (73%) appeared to have
therapeutic responses to risperidone. Risperidone doses were low (0.75-2.5 mg
daily) and clinical responses were observed at times within days of receiving the
medication. Improvement was clinically judged to be moderate to marked in 7 of 8
children. In addition, the treatment of 2 children was stopped because of
drowsiness; one also experienced a weight gain of 6 kg (13 lbs). An additional
child with autism and aggressive behavior who lacked affective symptoms did not
respond to risperidone. None of the children showed behavioral deterioration.
Seven of the 8 responders were taking concurrent medications; including 4 on mood
stabilizing medications (either lithium, carbamazepine, or valproic acid) in
subtherapeutic doses. Even in combination with other medications, side effects at
these doses were minimal and limited to mild sedation and, at times, troubling
weight gain. Pending controlled studies, these preliminary findings suggest that
risperidone--alone or in combination with mood stabilizers--may be of value in
treating children and adolescents with mood disorders (especially subthreshold
bipolar disorder) and aggressive behavior.
PMID- 9639080
TI - Combination treatment with clomipramine and selective serotonin reuptake
inhibitors for obsessive-compulsive disorder in children and adolescents.
AB - Medication management of obsessive-compulsive disorder (OCD) has consisted of
monotherapy with either clomipramine (CMI) or selective serotonin reuptake
inhibitors (SSRIs) such as fluvoxamine, paroxetine, or sertraline. Frequently,
OCD patients receiving monotherapy experience low treatment response rates and
problematic side effects that may result in discontinuation or noncompliance.
This open-label case series presents 7 patients (6 male, 1 female) ages 9 to 23
years with OCD who were effectively treated with combination of CMI plus an SSRI.
Treatment effects persisted through 5 to 22 months of follow-up from onset of
combination therapy. The drug combination was effective in the 2 patients with
OCD and no mood/anxiety comorbidity. Side effects appeared in 5 of 7 patients;
cardiovascular side effects were the most common adverse effects. Two patients
had prolongation of QTc intervals and 2 developed tachycardia while taking CMI
and SSRI combinations. Other risks might include serotonin syndrome, manic
switch, insomnia, and possibly headaches, EPS, and sexual dysfunction.
Recommendations are made to monitor electrocardiograms, CMI blood concentrations,
and vital signs in all cases because SSRIs can increase the blood levels of CMI
and/or its active metabolite, desmethylclomipramine (DCMI). CMI could also
potentially increase SSRI absorption and/or protein binding. The use of CMI and
SSRI combination therapy was found to be more effective compared with their
monotherapy in all 7 cases.
PMID- 9639081
TI - Paroxetine treatment of trichotillomania in an adolescent.
AB - The authors present a case report involving an adolescent with trichotillomania
who was treated with paroxetine. A significant reduction in symptoms was apparent
after two weeks of treatment. Dose was gradually increased to 30 mg of paroxetine
per day, which was well tolerated without any significant adverse events. The
authors discuss potential treatment implications of this case.
PMID- 9639082
TI - Manic behaviors associated with fluoxetine in three 12- to 18-year-olds with
obsessive-compulsive disorder.
AB - In a sample of 40 youths (ages 11-17) with obsessive-compulsive disorder (OCD)
and mood disorders who were treated with behavior therapy, 20 patients received
serotonin reuptake inhibitors (SRIs) and 20 did not. In open-label clinical
treatment, 30% of the patients (6/20) treated with SRIs developed manic or
hypomanic symptoms (5/15 on fluoxetine, 1/1 on sertraline). Symptoms included
impulsivity, grandiosity, pressured speech, and disinhibition and did not
resemble akathisia or "behavioral activation." These behaviors emerged despite
gradual dose elevation (2-5 mg/wk), conservative dosing (maximum 40 mg daily),
and careful weekly outpatient monitoring of each patient. Fluoxetine-induced
mania occurred at doses as low as 10 mg daily. It is unclear whether
mania/hypomania would appear in OCD children without comorbid mood disorders or,
alternatively, whether OCD is a stronger risk factor than mood disorder for manic
switch in SRI-treated youths. Clinicians are advised to be aware of the risk and
to be vigilant in monitoring manic and hypomanic behaviors when using SRIs to
treat OCD in youth, even with low doses and gradual dose elevation.
PMID- 9639083
TI - Gabapentin in the treatment of adolescent mania: a case report.
AB - Gabapentin is a new antiepileptic drug with an unknown mechanism of action and
very favorable pharmacokinetic and safety profiles. An increasing number of
reports have described the successful use of gabapentin in bipolar disorder in
adults. A 13-year-old boy with bipolar I disorder, manic episode, and ADHD, was
treated with gabapentin 1,500 mg/day as add-on therapy to carbamazepine and
showed a marked response within 1 month. He had previously failed a divalproex
trial, could not tolerate lithium, and carbamazepine could not control his
symptoms and induced a low WBC. He remained euthymic 7 months after gabapentin
was added. His Young Mania Rating Scale (YMRS) score was 27 when gabapentin was
added, 9 after 1 month, 15 after 4 months, and 6 after 7 months. Controlled
studies are needed to evaluate the possible anti-manic, mood stabilizing, and/or
anti-depressant properties of gabapentin in youth.
PMID- 9639084
TI - Sialic acid-binding lectin with antibacterial activity from the horse mussel:
further characterization and immunolocalization.
AB - A heterogeneous sialic acid-binding lectin with affinity for bacterial LPS was
isolated and partially characterized from hemolymph of the horse mussel Modiolus
modiolus.(1) Using two-dimensional electrophoresis with immobilized pH gradients,
the lectin revealed three subunits with different molecular weight and
isoelectric points (pI); Mr14 (pI approximately 5.1 and approximately 5.5), 17.5
(pI approximately 5.5) and 20 (pI approximately 4.9) kDa. The affinity purified
lectin existed in its native state as aggregates, and by stepwise centrifugation
it could be fractionated into molecular entities with distinct specificities
towards human and/or horse erythrocytes (modiolin H and/or E activity,
respectively). While the medium size entities (range < or = 30 and < 100 kDa)
exhibited only modiolin E activity and the lowest size entities (range < or = 5
and < 10 kDa) demonstrated only modiolin H activity, the largest aggregates (> or
= 100 kDa-)expressed both activities. Antibacterial activity of the lectin has
been observed against various marine bacteria, whereas the whole hemolymph was
less effective. The lectin exhibited strong antibacterial effect against all
tested strains of Vibrio anguillarum, Vibrio salmonicida, Vibrio viscosus, Vibrio
wodanis, and Vibrio ordalii, slight effect on Aeromonas salmonicida salmonicida
and Shewanella putrefaciens, and no inhibitory effect with Alteromonas sp.
Hemolymph of the horse mussel demonstrated no antibacterial effect against A.
salmonicida salmonicida, Alteromonas sp., Sh. putrefaciens and some strains of V.
anguillarum, but slight effects against some strains of V. anguillarum and both
strains of V. ordalii, and more predominantly against V. wodanis, V. salmonicida
and V. viscosus. These results indicate that the lectin plays a role in
elimination of bacteria. Circulating hemocytes were demonstrated to be the source
of the lectins since granules of the hemocytes were immunoreactive to anti
hemolymph lectin antibody and protein A/gold labelling.
PMID- 9639085
TI - Differential production of active oxygen species in photo-symbiotic and non
symbiotic bivalves.
AB - We investigated the generation of active oxygen species in the bivalves,
Crassostrea gigas, Fulvia mutica and Tridacna crocea in order to understand the
defensive mechanisms in giant clams that allow a stable association with
symbiotic zooxanthellae. C. gigas produced active oxygens, superoxide anion and
nitric oxide upon stimulation by phorbol myristate acetate. F. mutica generated a
little amount of superoxide anion and nitric oxide, and contained significant
phenoloxidase activity which catalyzes formation of quinones. T. crocea did not
generate any apparent active oxygen species or quinones. The importance of
lacking rapid cytotoxic responses consisting of active oxygen species to foreign
organisms in the symbiotic clam is discussed.
PMID- 9639086
TI - Evidence for antigen recognition by nonspecific cytotoxic cells: initiation of 3H
thymidine uptake following stimulation by a protozoan parasite and homologous
cognate synthetic peptide.
AB - Catfish nonspecific cytotoxic cells bind to and lyse certain protozoan parasites
and tumor cells. Target cell binding is facilitated by recognition of (minimally)
one antigenic determinant. Binding to this determinant initiates multiple
signalling pathways in NCC including protooncogene kinase phosphorylation,
regulation of phosphatase activity and increased membrane receptor expression. In
the present study, highly purified NCC were activated in vitro with the protozoan
parasite Tetrahymena pyriformis, with a multiple antigenic peptide (MAP) composed
of the cognate antigenic determinant of this parasite (i.e. natural killer target
antigen/NKTag) and NCC were activated with a monoclonal antibody specific for the
NCC receptor which binds NKTag. NCC were purified by Percoll density gradients
and negative selection by panning (2x) over anti-sIg specific mab 9E1. In 5 day
proliferation experiments, treatment of NCC with immobilized Tetrahymena
initiated a significant increase in uptake of tritiated thymidine. This appeared
to be a primary response in that NCC from in vivo parasite primed catfish did not
have secondary-like proliferation responses. Stimulation of NCC with immobilized
synthetic peptides composed of the cognate antigenic determinant of this parasite
(i.e. MAP) also caused significant increased uptake of tritiated thymidine. An
indication that NCC recognize a specific antigenic determinant was that sMAP
(i.e. peptides composed of the same amino acids as MAP but in a scrambled
sequence) failed to increase incorporation. Similar to the MAP results, mab 5C6
binding to NCC also caused increased thymidine uptake. To determine if an IL-2
cosignal was required to achieve optimum activation responses by NCC, different
concentrations of human recombinant IL-2 (rHuIL-2) were tested individually or as
costimulants. Co-treatment of NCC with rHuIL-2 and any of the three stimuli
(parasite, MAP, mab 5C6) did not produce increased proliferation of NCC. These
studies demonstrated that NCC specifically recognize an antigenic determinant on
protozoan parasites and binding to this antigen produces an activation signal
that may have important consequences for elicitation of innate immunity.
PMID- 9639087
TI - Intracellular signaling events in superoxide generation and adhesion of channel
catfish, Ictalurus punctatus rafinesque, neutrophils to the extracellular matrix
protein fibrinogen.
AB - Activation of channel catfish neutrophils is essential if these cells are to
participate in adhesion to extracellular matrix proteins or generate
intracellular superoxide for killing of microbes. Various signaling pathways are
required for these activities to occur. The objective of this study was to
identify components of the signal transduction pathways in channel catfish
neutrophils. A23187, bryostatin, and phorbol dibutyrate (PDBU) all induced
catfish neutrophil adhesion to fibrinogen coated plates and the adhesion could be
significantly reduced when neutrophils were pretreated with staurosporine (1 x
10(-7) M). Staurosporine was the only inhibitor used in the study that inhibited
or reduced PDBU-induced adhesion of catfish neutrophils to fibrinogen. Phorbol
dibutyrate at the concentrations used in the adhesion assay was the only
stimulant that caused generation of intracellular superoxide and therefore was
the only stimulant used in the remainder of the study. Aristolochic acid (1 x 10(
4) and 3 x 10(-5) M) + PDBU and staurosporine (1 x 10(-7) and 1 x 10(-8) M) +
PDBU caused a significant decrease (p < or = 0.05) in PDBU-induced intracellular
oxygen generation. The role of protein kinase C and phospholipases in channel
catfish neutrophil adhesion and superoxide generation are discussed.
PMID- 9639088
TI - A comparative study of pentraxin-like proteins in different fish species.
AB - Pentraxins are a family of pentameric serum proteins that have been conserved in
evolution and share sequence homology, similar subunit assembly and the capacity
for calcium-dependent ligand binding. The classical pentraxins are human C
reactive protein (CRP) and serum amyloid P component (SAP). The sequence homology
and gene organization indicate that they arose from a gene duplication of an
ancestral pentraxin gene. They are usually isolated based on their affinity for
phosphorylcholine and agarose, respectively. We have used this method for
isolation of pentraxin-like proteins from normal serum of Atlantic salmon (Salmo
salar), common wolffish (Anarhichas lupus), cod (Gadus morhua) and halibut
(Hippoglossus hippoglossus). Although pentraxin structures have not been
verified, the isolated proteins all appear to be pentraxin-like based on their
binding specificity, molecular weight of subunits, cross-reactivity with
antibodies to human pentraxins and N-terminal amino acid sequences. However, with
the described method only one pentraxin-like protein was detected in each of the
fish species.
PMID- 9639089
TI - In vitro cell-mediated cytotoxicity against allogeneic erythrocytes in ginbuna
crucian carp and goldfish using a non-radioactive assay.
AB - Cell-mediated cytotoxicity of clonal ginbuna crucian carp leukocytes against
allogeneic erythrocytes is described using a sensitive non-radioactive in vitro
assay. Hemoglobin released from target erythrocytes after cell-mediated
erythrolysis was detected by tetramethylbenzidine (TMB). TMB assay showed clear
correlation with a 51Cr-release assay and even exhibited higher cytotoxicity. The
use of erythrocytes as target cells has several advantages over a conventional
51Cr-release assay. Erythrocytes do not have cytotoxic activity, are relatively
homogeneous, are available in large numbers and erythrocyte donors need not be
killed. Leukocytes from fish sensitized by erythrocyte injection or scale
grafting efficiently lysed allogeneic erythrocytes, but did not kill isogeneic or
autologous erythrocytes. In contrast, leukocytes from unsensitized fish did not
lyse allogeneic erythrocytes and repeated sensitizations by allogeneic grafts
were necessary to induce cytotoxic cells. Effector cells isolated from peripheral
blood showed a higher cytotoxic effect toward allogeneic target cells than
effector cells isolated from kidney. These studies support the hypothesis that
fish are capable of a genetically restricted specific cell-mediated cytotoxicity.
PMID- 9639090
TI - Isolation and initial characterisation of complement components C3 and C4 of the
nurse shark and the channel catfish.
AB - Complement components C3 and C4 have been isolated from the serum of the nurse
shark (Ginglymostoma cirratum) and of the channel catfish (Ictalurus punctatus).
As in the higher vertebrates, the fish C4 proteins have three-chain structures
while the C3 proteins have two-chain structures. All four proteins have intra
chain thioesters located within their highest molecular mass polypeptides. N
terminal sequence analysis of the polypeptides has confirmed the identity of the
proteins. In all cases except the catfish C3 alpha-chain, which appears to have a
blocked N-terminus, sequence similarities are apparent in comparisons with the
chains of C3 and C4 from higher vertebrates. We have confirmed that the
activity/protein previously designated C2n is the nurse shark analogue of
mammalian C4. This is the first report of structural evidence for C4 in both the
bony and cartilaginous fish.
PMID- 9639091
TI - Natural cytotoxicity towards allogeneic tumour targets in Xenopus mediated by
diverse splenocyte populations.
AB - We have recently demonstrated NK-like activity in the spleen of the clawed frog,
Xenopus laevis. This paper investigates the cellular basis of this natural
cytotoxicity. Significant levels of cytotoxicity towards B3B7 allogeneic thymus
tumour targets, that express neither class Ia nor class II MHC proteins, occurred
after splenocytes from either control or early-thymectomized (Tx) year-old
Xenopus were cultured for 48 hours. Killing by Tx cells required their culture in
growth factor-rich medium (GFM) obtained from concanavalin A-stimulated cells.
Immunomagnetic cell sorting revealed that cytotoxic effectors in both control and
Tx frogs were found in the B cell-depleted population, but never in the B cell
enriched fraction. Splenocytes from control Xenopus, depleted of T cells by
magnetic sorting and following culture in GFM, also developed natural
cytotoxicity towards allotumour cells. Magnetic cell sorting also revealed that
purified (CD5+) T cells cultured for 48 hours in GFM also became able to lyse the
allogeneic tumour targets. Cytotoxicity mediated by T cells resided not only in
the CD5+, CD8+ population, but also in the CD5+, CD8- (putative CD4+) T cell
subset. Ontogenetic studies revealed that splenocytes from 6-7 week-old (stage 56
57) control larvae, even after 48 hr culture in GFM, were unable to spontaneously
lyse the allotumour targets, whereas cultured splenocytes from 6 month old
froglets were effective killers. Thymocytes from larvae or adults routinely
failed to kill tumour cells. The work highlights the need to use Tx Xenopus to
further explore non-T-cell-mediated, NK-like cytotoxicity at the amphibian level
of evolution.
PMID- 9639092
TI - The complement system of the marsupial Monodelphis domestica.
AB - The activation requirements and pathways of the serum C' system of the marsupial
Monodelphis domestica were characterized using standard hemolytic procedures. The
existence of distinct classical and alternative activation pathways was
established on the basis of their ionic requirements, hemolytic capacity at
different temperatures, kinetics of hemolysis, and differential susceptibility to
the classical pathway inhibitor carrageenan. For the most part, the activities of
these pathways were influenced by factors and conditions in a manner similar to
the way they affect the activity of eutherian complement. These observations
provide further support for the idea that Monodelphis domestica would serve as a
useful model for comparative immunological studies in mammals.
PMID- 9639093
TI - Age-dependent remodeling of peripheral blood CD4+ CD8+ T lymphocytes in
cynomolgus monkeys.
AB - Recently, we have found in adult cynomolgus monkeys that substantial peripheral
blood CD4+ CD8+ double-positive (DP) T lymphocytes exhibit a resting memory
phenotype and increase in proportion with age. In this study, we investigated
whether phenotypic changes occur in the course of the increase in proportion of
the DP T cells. The results obtained from 195 clinically healthy monkeys aged
from 1 month to 31 years showed that the CD29hi and CD28 subpopulation in the DP
T subset increased in proportion with age and that the increase reached a plateau
at six years old for the CD29hi subpopulation and at eleven years old for the
CD28 one, respectively. The phenotypic alteration preceded the abrupt increase in
proportion of the DP T cells and was able to be classified into four phases on
the basis of the qualitative and quantitative alteration.
PMID- 9639094
TI - LAMP-1/ESGp appears on the cell surface of single celled mouse embryos subsequent
to fertilization.
PMID- 9639095
TI - Validation of routine mycoplasma testing by PCR.
PMID- 9639096
TI - A clonal chondrocytic cell line derived from BMP-2/T antigen-expressing
transgenic mouse.
PMID- 9639097
TI - Primary human vascular smooth muscle cell culture enhanced by human umbilical
cord serum.
PMID- 9639098
TI - Establishment of monk seal cell lines.
PMID- 9639099
TI - Culture and characterization of sinusoidal endothelial cells isolated from human
liver.
AB - Although most vascular models use large vessel endothelial cells from human
umbilical veins, there is marked heterogeneity among endothelial cells from
different vascular beds and organs. More accurate modeling of endothelial
involvement in liver diseases, including metastasis, may result from the use of
human hepatic sinusoidal endothelial cells. Liver resection specimens were
sectioned, then treated with a 1.2 U/ml dispase solution. The tissue slurry was
mechanically disaggregated and separated by centrifugation on a Percoll density
gradient. Cells were then cultured in an endothelial-specific media with growth
factors. These techniques resulted in a homogeneous monolayer consistent with
endothelial cells by light microscopy. An endothelial origin was further
confirmed by the expression of Factor VIII, binding of Ulex lectin, and uptake of
acetylated low density lipoprotein. Electron microscopy showed transcellular
fenestrations consistent with a sinusoidal origin. These human hepatic sinusoidal
endothelial cells were then studied for expression of the adhesion molecules
CD31/PECAM, CD34, E-selectin, ICAM-1, L-selectin, LFA-3, P-selectin, and VCAM-1
plus the binding of wheat germ agglutinin lectin. The patterns of adhesion
molecule expression and lectin binding by these cells are characteristic of
hepatic sinusoidal endothelia. In this paper, we have described a method for
isolation and culture of human cells with the morphologic and phenotypic
characteristics of hepatic sinusoidal endothelia.
PMID- 9639101
TI - The proliferation of mouse mammary epithelial cells in response to specific
mitogens is modulated by the mammary fat pad in vitro.
AB - The ability of the murine mammary fat pad to directly stimulate the growth of
mammary epithelial cells and to modulate the effects of various mammogenic agents
has been investigated in a newly described, hormone- and serum-free coculture
system. COMMA-1D mouse mammary epithelial cells were cultured for 5 or 7 d with
various supplements in the absence or presence of epithelium-free mammary fat pad
explants from virgin female BALB/c mice. Cocultured fat pad stimulated increases
in the DNA content of COMMA-1D cultures by two- to threefold or six- to eightfold
after 5 or 7 d, respectively. The mitogenic effect was additive to that of 10%
fetal calf serum and could not be attributed to the release of prostaglandin E2
or synthesis of prostaglandins by epithelial cells. In addition, bovine serum
albumin attenuated (P < 0.05) the mitogenic effect of cocultured mammary fat pad.
Added alone, insulinlike growth factor-I, epidermal growth factor, and insulin
increased (P < 0.05) total DNA of COMMA-1D cultures by 2.5-, 3.7-, and 2.3-fold,
respectively. Cocultured mammary fat pad markedly interacted (P < 0.01) with
these mitogens to yield final DNA values that were 21.2-, 13.3-, and 22.1-fold
greater than in basal medium only. Associated with this proliferation was the
formation of numerous domes above the COMMA-1D monolayer. There was no
proliferative response to growth hormone or prolactin in the absence or presence
of cocultured fat pad (P > 0.05). Whereas hydrocortisone did not alter cell
number, it attenuated (P < 0.05) the mitogenic effect of cocultured mammary fat
pad. These results indicate that the murine mammary fat pad is not only a direct
source of mitogenic activity, but also modulates the response of mammary
epithelial cells to certain mammogens.
PMID- 9639100
TI - Cytokine inducible matrix metalloproteinase expression in immortalized rat
chondrocytes is independent of nitric oxide stimulation.
AB - The objective of this study was to determine if an immortalized mammalian
chondrocyte cell line had a profile of matrix metalloproteinase (MMP) expression
that was consistent with what has been reported for primary chondrocytes in vitro
and in vivo. A combination of zymography, Western, and Northern analysis was used
to examine the expression of MMPs that are relevant to cartilage degradation.
Both interleukin-1beta and tumor necrosis factor alpha induced a 4- to 9-fold
increase in the level of MMP-9 expression in conditioned media, and a 17- to 24
fold increase in MMP-3 mRNA. Other compounds such as basic fibroblast growth
factor and staurosporine each increased MMP-9 expression individually and
potentiated the effects of the two cytokines. Transforming growth factor beta had
no positive or inhibitory effects. N-methyl arginine blocked the increase in
nitric oxide observed following treatment with the cytokines but did not prevent
the increased expression of MMPs. The pattern of metalloproteinase expression
observed in IRC cells and the response to cytokines is very similar to what has
been reported during the pathogenesis of osteoarthritis. The IRC cells should be
useful as a model system to study basic mechanisms controlling chondrocyte MMP
expression and to identify pharmacological modulators of this process.
PMID- 9639102
TI - Ultrastructural and functional study of the liver pigment cells from Rana
esculenta L.
AB - A study of the liver pigment cells of Rana esculenta L. has been performed on
both liver in toto and cells in culture. Ultrastructural and cytochemical
analyses showed a close relationship between this visceral pigment cell system
and the cells of hepatic macrophage lineage. Like the latter, the liver pigment
cells present phagocytic activity, in the sinusoids and in vitro, and give a
positive response to tests for peroxidase and lipase. The liver pigment cells are
isolated, together with the Kupffer cells, from the sinusoidal cell fraction of
the liver. In culture, they maintain their melanogenetic ability, demonstrated by
the presence of dopaoxidase activity in the soluble, membranous, and melanosome
fractions. Analysis of the cultures showed that as culture time increased, so did
melanosome dopaoxidase activity, the number of pigmented fields, and the level of
pigmentation of the cells. The values of dopaoxidase activity of the pigment
cells in culture show the same seasonal oscillations as the system in toto,
indicating that the cells maintain an internal clock, at least in the first 72 h
of culture. There is evidence that the pigment cells are macrophages which can
express a melanogenetic function. Our results and other experimental data provide
a basis for hypothesizing that the pigment cells in Rana esculenta L. liver may
derive from, or have a common origin with, the Kupffer cells.
PMID- 9639103
TI - Direct cloning of astrocytes from primary culture without previous
immortalization.
AB - In primary cultures, much evidence shows the existence of different subtypes of
astrocytes that are not all identified. One methodology for studying these
subtypes can be their cloning. The present investigation shows a method for a
direct cloning of astrocytes without previous immortalization. Astrocytes from
the cerebral cortex of newborn rats were cultured, purified by shaking, and
harvested by trypsinization. One single astrocyte was plated in a small volume of
a homemade cloning medium. After getting a colony, successive platings were made
using larger and larger vessels, up to 60-mm-diameter petri dishes. Then,
subcultures were made. The yield of the cloning was similar to that of common
eukaryotic cell clonings. All along the cloning procedure, the cells were
positively immunostained with anti-glial fibrillary acidic protein antibodies.
Cloned cells from some batches were spindle-shaped, looking like fibroblasts.
Nevertheless, they were immunostained with anti-glial fibrillary acidic protein
antibodies, unlike true fibroblasts. These spindle-shaped astrocytes were
compared to cells from an astrocytoma cell line that had the same shape. The
growth pattern of the astrocytoma cells was different from that of the astrocytes
cloned from the primary cultures. All the types of studied cells contained
glycogen. On the basis of the criteria of morphology, of glial fibrillary acidic
protein immunolabeling, and of glycogen synthesis, the cloned cells kept the
characteristics of astrocytes. This study shows that it is perfectly possible to
get clones of astrocytes from one astrocyte without previous immortalization,
giving thus a convenient material for the study of astrocyte biology.
PMID- 9639105
TI - An in vitro approach for the characterization of the cycling B cell response.
AB - Because isolation of sufficient numbers of cycling, germinal center B cells from
mice for biochemical characterization of BCR-derived signals can be problematic,
we have designed an experimental approach for generating large numbers of cycling
B cells for further study. In the experiments reported here, small, resting B
cells were polyclonally stimulated with lipopolysaccharide (LPS), and cycling B
cells isolated as two bands on three-step Percoll gradients. Cycling B cells
isolated at Days 2, 4, or 6 of preactivation showed an increased expression of
Fas receptor and peanut agglutinin binding, with a concomitant decrease in sIgD
positivity. These cells phenotypically resembled extrafollicular or early
germinal center B cells. These cycling B cells were used to study the functional
consequences of differential signaling through the BCR. Strong cross-linking of
BCR, by restimulation of cycling normal B cells with either immobilized or
soluble F(ab')2 anti-mu and cycling hen egg lysozyme (HEL) transgenic B cells
with either soluble or immobilized HEL, extended cellular proliferation by 2-3 d.
In contrast, cycling B cells either restimulated with soluble, whole anti-mu (to
mimic binding of soluble immune complexes) or cultured in the absence of
restimulation (to mimic cycling B cells not competitive for antigen) resulted in
the rapid exit of the cells from cycle. This system will enable the molecular and
biochemical characterization of signal delivery to cycling B cells.
PMID- 9639104
TI - Autocrine secretion of TGF-beta 1 and TGF-beta 2 by pre-adipocytes and
adipocytes: a potent negative regulator of adipocyte differentiation and
proliferation of mammary carcinoma cells.
AB - We have developed an in vitro system to examine the influence of adipocytes, a
major mammary stromal cell type, on the growth of a murine mammary carcinoma,
SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor,
hepatocyte growth factor, which strongly stimulates proliferation of SP1 cells.
We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which
inhibit DNA synthesis in SP1 cells. In addition, latent inhibitory activity is
present in conditioned media (CM) from both pre-adipocytes and adipocytes, and is
activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild
type epithelial cells, but not DR27 mutant epithelial cells which lack TGF-beta
type II receptor. Inhibitory activity of CMs was partially abrogated by
neutralizing anti-TGF-beta1 and anti-TGF-beta2 antibodies, and was removed
following ultrafiltration through membranes of 10,000 Mr but not 30,000 Mr pore
size. These results show that the inhibitory effect on DNA synthesis is mediated
by TGF-beta1-like and TGF-beta2-like molecules. In addition, acid-treated CM as
well as purified TGF-beta inhibited differentiation of pre-adipocytes. Untreated
pre-adipocyte CM, but not mature adipocyte CM, spontaneously inhibited adipocyte
differentiation. Together, these findings indicate that pre-adipocytes
spontaneously activate their own secreted TGF-beta, whereas mature adipocytes do
not, and suggest that activation of TGF-beta has a potent negative regulatory
effect on adipocyte differentiation and tumor growth. Thus, TGF-beta may be an
important modulator of tumor growth and adipocyte differentiation via both
paracrine and autocrine mechanisms. These findings emphasize the importance of
adipocyte-tumor interactions in the regulation of tumor microenvironment.
PMID- 9639106
TI - Chlorophyll and pheophytin derivatives in geochemical transformation pathways: a
surface-enhanced resonance Raman spectroscopic study.
AB - Protected surface-enhanced resonance Raman spectroscopy (PSERRS) has been used to
study a number of chlorophyll transformation products that have been suggested as
intermediates in the so-called Treibs hypothesis which describes the
transformation of ancient chlorophyll a (chl a) in the biosphere into
desoxophylloerythroetio-porphyrin (DPEP) found in sedimentary environments. Both
Soret- and Qy-resonant PSERR spectra have been recorded, providing two
dimensional structural fingerprints containing a number of bands which enable the
presence of specific peripheral substituents to be identified. Some of these
marker bands can be assigned directly to vibrational modes of the particular
substituents. This has allowed further characterization of the vibrational
spectrum of chl a; in particular, a vinyl mode has been identified which
previously was thought to be Raman silent.
PMID- 9639107
TI - Effect of surface modifiers on the electrode reactions and conformation of
cytochrome c3 adsorbed on a silver electrode.
AB - Surface-enhanced resonance Raman scattering and electroreflectance voltammetry
were used to investigate the effect of electrode surface modification on the
structure and redox properties of cytochrome c3 immobilized on Ag surfaces. It is
shown that the redox reactions of cytochrome c3 are more reversible at an 11
mercaptoundecanoic acid modified Ag electrode as compared to a bare metal
surface. The heme of cytochrome c3 is in a mixed low and high spin state when
adsorbed at the bare electrode, whereas only the low spin form is present on the
11-mercaptoundecanoic acid modified electrode, suggesting that the native
conformation is maintained in the latter case. The reduction potential is close
to that of the most positive macroscopic potential as determined by
electroreflectance spectroscopy. In contrast, the reduction potential as
determined by SERRS undergoes a large positive shift in the presence of 4,4'
bipyridine, the magnitude of which is dependent upon the concentration of 4,4'
bipyridine. These results indicate that the effect of the cytochrome c3
interaction with the 4,4'-bipyridine-modified surface is significantly different
as compared to its interaction with the 11-mercaptoundecaodoic acid modified
surface. Moreover, the results emphasize that electrode modifiers can have
dramatically different effects on the redox properties of different proteins. It
is well known that 4,4'-bipyridine acts as a redox promoter in the case of
cytochrome c, whereas no electrochemical or electroreflectance response was
observed in the case of cytochrome c3.
PMID- 9639108
TI - Raman linear intensity difference of membrane-bound peptides: indole ring
orientations of tryptophans 11 and 13 in the gramicidin A transmembrane channel.
AB - A Raman linear intensity difference (RLID) method has been developed to determine
orientations of chromophores in membrane-bound peptides and proteins. The method
involves orientation of the peptide or protein in lipid bilayer membranes and
measurement of intensity differences between Raman spectra excited with two
orthogonal laser polarizations. Analysis of the RLID spectrum is simplified when
the chromophore exhibits a vibrational mode for which the Raman band is enhanced
through resonance with a single molecular electronic transition. To examine the
indole ring orientations of Trp residues in the gramicidin A transmembrane
channel, we have prepared analogues of gramicidin A, in which one of four Trp
residues is replaced by deuterated Trp (Trp-2,4,5,6,7-d5). Two vibrational Raman
bands omega(d)3 and omega(d)2 of deuterated Trp have been shown to gain intensity
predominantly through resonance with the Bb and La electronic transitions,
respectively, when excited at 244 and 257 nm. By examining the RLID spectra of
the omega(d)3 and omega(d)2 bands of gramicidin A channels oriented in
phospholipid bilayer membranes, we have determined the inclination angles of the
Bb and La transition moments with respect to the channel axis in the absence and
presence of Na+. The orientations of the Trp-11 and Trp-13 indole rings in the
gramicidin channel structure have been derived from the inclination angles of the
transition moments. The indole rings of Trp-11 and Trp-13, which are known to
shift along the channel axis upon binding of Na+, do not reorient during their
positional shifts.
PMID- 9639109
TI - A spectroscopic study of the hydrogen bonding and pi-pi stacking interactions of
harmane with quinoline.
AB - A spectroscopic (UV-vis, Fourier transform IR, steady state, and time-resolved
fluorescence) study of the interactions of the ground and excited singlet states
of harmane (1-methyl-9H-pyrido/3,4-b/indole) with quinoline has been carried out
in cyclohexane, toluene, and buffered pH=8.7 aqueous solutions. To analyze how
the number of rings in the substrate influences these interactions, pyridine and
phenanthridine have also been included in this study. In cyclohexane and toluene
1:1 stoichiometric hydrogen-bonded complexes are formed in both the ground and
the excited singlet states. As the number of rings of the benzopyridines and the
solvent polarity increase hydrogen-bonding interactions weaken and pi-pi van der
Waals interactions become apparent.
PMID- 9639110
TI - The binding of biotin analogues by streptavidin: a Raman spectroscopic study.
AB - Raman spectra of anhydrous complexes of streptavidin (Strep) with biotin (Bio)
and some Bio analogues [Biotin methyl ester (MEBio), desthiobiotin (DEBio), 2'
iminobiotin (IMBio), and diaminobiotin (DABio)] were recorded. The vibrational
results indicate that the interaction with some of these ligands is able to
modify the overall structure of the protein and this binding results in a
decrease in the beta-sheet content and an increase in the alpha-helix content. To
further confirm the conformational changes of the protein structure due to Bio
analogue binding, the curve-fitting analysis of the amide I Raman band of neat
Strep and of the complexes were performed. The intensity ratio of the components
due to the beta-sheet and alpha-helix conformations decreased in the Strep-MEBio,
Strep-IMBio (pH 11), and Strep-Bio systems, whereas in all the other systems the
changes were not significant. This behavior differs from that of Avi bound to the
same ligands and suggests that Strep and Avi differ in their binding selectivity.
A good correlation was found between the secondary structure percentages of the
Avi and of the Strep complexes and deltaG(o). On the basis of this linear
relationship, the vibrational results allow for an acceptable evaluation of the
dissociation constants of the Strep complexes, not previously reported in the
literature. The present results indicate a correlation between the type of
interaction and the effects of the protein-substrate bonding on the overall
structure of the proteins. The amino acid residues in the binding site appear to
be positioned in a such a way as to provide a precise fit of Bio. Even slight
change in the substrate structure causes a weakness in the strength of the
binding. The vibrational results confirm that both the imidazolidinone and the
thiophan rings are important in the Strep-Bio interactions, but the former is
more responsible for the high affinity of the binding. One of the Tyr residues is
hydrogen bound with the ureido ring and another Tyr could be involved in the
binding pocket. Trp residues do not directly bind the ligand and probably
stabilize other binding site residues which in turn interact directly with Bio.
PMID- 9639111
TI - Pressure-induced structural rearrangements of bovine pancreatic trypsin inhibitor
studied by FTIR spectroscopy.
AB - Fourier transform infrared (FTIR) spectroscopy combined with resolution
enhancement techniques, second-derivative and difference spectroscopies, have
been used to characterize pressure-induced changes in the structural
rearrangements of bovine pancreatic trypsin inhibitor (BPTI) in D2O solution at
25.0 degrees C. According to the observed changes in the amide I' band up to 550
MPa, the secondary structure elements of BPTI, such as the alpha-helix, 3(10)
helix, beta-sheet, and beta-turn, are scarcely rearranged except for the loop
structure of residues of 9-17 and 36-43. The polypeptide backbone is not
extensively unfolded up to 550 MPa. The minor pressure-induced structural
rearrangements are completely reversible. A further increase in pressure above
1000 MPa associated with the precipitation of BPTI in D2O buffer solution induces
the partial structural rearrangements of the alpha-helix, beta-turn and/or 3(10)
helix, and beta-sheet. The polypeptide backbone of BPTI is not fully unfolded
even above 1000 MPa. Most of the protected backbone amide protons involved in the
beta-sheet remain intact in the pressure range where BPTI is not precipitated,
while those involved in the alpha-helix and beta-turn and/or 3(10)-helix are
exchanged with solvent deuterons. The protected backbone amide protons located
near the surface regions are more easily exchanged with solvent deuterons by
application of high pressure than those involved in the core.
PMID- 9639112
TI - Why classify basal cell carcinomas?
AB - Basal cell carcinoma of the skin is the commonest form of cancer in the white
population. A simple pathological classification is presented and recommended for
general use to aid clinicians in their management of cases. Basal cell carcinoma
can be classified as nodular, infiltrative, superficial apparently multifocal and
mixed in terms of the histological growth pattern. These patterns can be related
to the likelihood of complete excision and, if excision is incomplete, to the
frequency of recurrence.
PMID- 9639113
TI - Ki67 expression in lichen sclerosus of vulva in patients with and without
associated squamous cell carcinoma.
AB - AIMS: To investigate the malignant potential of lichen sclerosus, a study using
the cell proliferation marker Ki67 comparing lichen sclerosus with and without
associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin
fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated
carcinoma, and 31 cases without associated carcinoma, including 16 random cases,
seven with epidermal thickening and eight with epidermal thinning, were examined
by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67
reactivity was mostly seen in the basal and parabasal cells in both groups of
lichen sclerosus and this pattern was similar to normal skin, squamous cell
hyperplasia and analogous to that of one form of squamous cell carcinoma. There
was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with
associated squamous cell carcinoma; however, in squamous cell hyperplasia
adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In
lichen sclerosus without associated carcinoma, the random cases had a count of 53
per 100 basal cells, those with epidermal thickening 53 and those with thinning
42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION:
The lack of qualitative differences of Ki67 expression in normal skin, in lichen
sclerosus with and without carcinoma, in squamous cell hyperplasia and in one
form of squamous cell carcinoma indicates that these conditions share a common
localized pattern of cell proliferation and does not support or deny the
malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell
hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to
the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened
lichen sclerosus compared to thinned suggests that some or all of the cases of
thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia
or that lichen simplex chronicus superimposed on lichen sclerosus has a higher
Ki67 expression or that the distinction between squamous cell hyperplasia and
lichen simplex chronicus is only one of terminology.
PMID- 9639114
TI - Nerve sheath tumours with hybrid features of neurofibroma and schwannoma: a
conceptual challenge.
AB - AIMS: To characterize and delineate a subset of rare nerve sheath tumours showing
hybrid features of neurofibroma and schwannoma. METHODS AND RESULTS: Nine lesions
were identified in the authors' files showing predominant features of
neurofibroma with distinct, often nodular regions of classical schwannomatous
differentiation. Most patients were adults, eight out of nine were male. Of the
nine lesions, two were dermal, two were subcutaneous and five were subfascial.
Five lesions had a plexiform architecture and one patient had overt
neurofibromatosis. One out of six patients with follow-up developed local
recurrence. Schwannoma-like regions displayed strong S100 staining, in contrast
to more varied and limited S100 reactivity in neurofibromatous areas. The Antoni
A areas could be quite cellular with high MIB-1 proliferation indices. No lesion
underwent malignant change. CONCLUSIONS: Our results demonstrate that some nerve
sheath tumours may contain histologically clear components of both neurofibroma
and schwannoma, suggesting that (despite evident and well-defined
clinicopathological differences) these two lesions may be even more closely
related than previously recognized. Whether this phenomenon results from a
localized microenvironmental change or from a clonal genetic alteration remains
unknown.
PMID- 9639115
TI - Vascular endothelial cadherin is expressed by perineurial cells of peripheral
nerve.
AB - AIMS: To study the distribution of vascular endothelial (VE) cadherin in
peripheral nerves. METHODS AND RESULTS: Using two monoclonal antibodies that
detect VE-cadherin (TEA1.31 and 7B4) an immunohistochemical study of VE-cadherin
expression in five common peroneal nerve biopsies and five skin specimens
containing small peripheal nerves was performed. VE-cadherin was consistently
expressed by the perineurium of nerves but not by other nerve elements such as
Schwann cells or axons. CONCLUSION: This report indicates that VE-cadherin is
not. as was previously thought, a specific marker of endothelial cells and
further defines the phenotype of the perineurial cell. The established role of VE
cadherin in controlling the permeability of vascular endothelium suggests that
this molecule may have a similar role in the perineurium. VE-cadherin may
therefore be important in the maintenance of the blood-nerve barrier, the
peripheral nerve equivalent of the blood-brain barrier.
PMID- 9639116
TI - Cellular 'neurothekeoma': an epithelioid variant of dermatofibroma?
AB - AIMS: Cellular neurothekeoma is a rare benign cutaneous neoplasm with conflicting
opinions regarding its histogenetic origin (nerve sheath, smooth muscle,
myofibroblasts) as well as its relation to myxoid neurothekeoma (nerve sheath
myxoma). The present series describes 15 cases whose clinicopathological features
indicate a relationship to dermatofibroma. METHODS AND RESULTS: In this
retrospective clinicopathological study, the lesions preferentially occurred in
adolescents to young adults on the upper half of the body, often clinically
diagnosed as some kind of fibrohistiocytic tissue response. Besides
characteristic whorled nests to fascicles of palely eosinophilic epithelioid
cells, all lesions showed variable clues pointing to dermatofibroma: acanthosis,
ill-defined storiform periphery, peripherally accentuated prominent sclerosis and
lymphocytic demarcation/infiltration. Immunohistochemically, all cases were
positive with NK1C3 (CD57), KiM1p and proliferating cell nuclear antigen, seven
were positive for neurone specific enolase, five for factor XIIIa, six for smooth
muscle specific actin and three for E9, an antimetallothionein marker. These
findings are similar to those of conventional dermatofibromas, the variability of
the profile being best explained by time cycle and function dependent changes.
Ultrastructurally, two cases showed microfilaments, attachment plaques, prominent
pinocytosis and focal remnants of basal lamina. A careful study of the data and
photomicrographs from the literature reveals that in many cases similar
conclusions could be reached. Obvious discrepancies are most likely due to the
confusion with myxoid neurothekeoma, a well circumscribed, more spindly and
myxoid, S100 positive lesion of Schwannian origin. CONCLUSION: The appearance of
dermatofibromas is markedly influenced by architectural, e.g. in deep penetrating
dermatofibroma, and/or cellular/stromal criteria, e.g. in epithelioid cell
histiocytoma or sclerosing dermatofibroma. Cellular neurothekeoma seems to be a
variant of dermatofibromas with both architectural and cellular/stromal
peculiarities, i.e. plexiform pattern, epithelioid cytology and stromal
sclerosis.
PMID- 9639117
TI - Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its
malignant transformation.
AB - AIMS: To clarify the association of p53 and CD34 expression with development of
malignant solitary fibrous tumour we have studied 10 cases of solitary fibrous
tumour arising in the pleura, retroperitoneum and pelvic cavity with
clinicopathological features of malignancy. METHODS AND RESULTS: Tumours were
localized solid masses with or without necrosis in eight and they nearly totally
occupied the pleural cavity in two. Basic histology of the tumours was the
proliferation of spindle cells arranged in 'patternless' pattern or in
interlacing bundles with nuclear atypia and mitotic activities of various degree.
In two, high-grade foci were present within low or intermediate-grade tumours.
Recurrent tumours also showed more atypical features than primary tumours in two.
Immunohistochemical studies showed CD34 positivity in seven, but three of them
showed marked diminution or complete loss of CD34 expression in high-grade foci
or a recurrent tumour. Three high-grade cases showed totally negative staining
for CD34. p53 was strongly expressed in cases with fatal outcome, clinical
recurrence, nuclear atypia, high mitotic activity or local invasion, whereas
almost negative in benign tumours. CONCLUSIONS: Malignant solitary fibrous
tumours may occur de novo or by transformation within benign or low-grade tumours
and may be associated with p53 mutation. Although CD34 is a useful marker in the
diagnosis of solitary fibrous tumour, one should bear in mind that its expression
can be lost in high-grade tumours.
PMID- 9639118
TI - Translocation 2;11 in a fibroma of tendon sheath.
AB - AIMS: To determine whether fibromas of tendon sheath represent a reactive
fibrosing process or whether they are neoplastic, we investigated the chromosomes
of the proliferating cells. A clonally occurring karyotypic abnormality would be
an argument in favour of these fibromas being neoplastic. METHODS AND RESULTS: A
biopsy specimen of a fibroma of tendon sheath was cultured after collagenase
exposure leading to dissociation of the tissue. The cultured cells were harvested
after 4 days and chromosome analysis done according to standard procedures. Ten
out of 20 karyotyped cells showed an identical chromosome abnormality
characterized by a t(2;11)(q31-32;q12). The other 10 cells showed a normal 46,XX
karyotype. CONCLUSION: The clonally occurring chromosome abnormality found in
this fibroma of tendon sheath suggests that this proliferation is neoplastic and
not a reactive fibrosing process.
PMID- 9639119
TI - A cytogenetic approach to the differential diagnosis of metastatic clear cell
renal carcinoma.
AB - AIMS: To determine by cytogenetic analysis the origins of two clear cell tumours
in a 70-year-old Caucasian woman, one in the thyroid gland, and the other in the
skin, 16 and 20 years, respectively, after tumour nephrectomy. We sought a
conclusive distinction between primary clear cell thyroid carcinoma and its
cutaneous metastasis, and between thyroid and cutaneous metastases of clear cell
renal carcinoma (RCC). METHODS AND RESULTS: Paraffin sections of the previously
formalin-fixed thyroid tumour, and the fresh cutaneous tumour were stained with
haematoxylin and eosin (H & E) and periodic acid-Schiff (PAS). Additionally,
samples of both tumours were examined electron microscopically.
Immunohistochemistry was performed with antibodies against thyroglobulin,
pancytokeratin, keratin 7, 8, 18 and 19, chromogranin, calcitonin, CEA, vimentin
and EMA. Five to six micrometre sections of both tumours were analysed with alpha
satellite probes of chromosomes 3, 7 and 17 using chromosomal in-situ
hybridization (CISH). The cutaneous tumour was also cultured and analysed
cytogenetically. The thyroid tumour displayed some follicle-like structures that
stained positive with both PAS and antithyroglobulin, giving evidence of possibly
entrapped thyroid follicles in metastatic RCC. The cutaneous tumour was negative
for both stains. The tumours were ultrastructurally completely devoid of
neurosecretory granules. Classical cytogenetical analysis of the cultured
cutaneous tumour cells revealed monosomies 3 and 14, well-known specific primary
and secondary aberrations, respectively, in clear cell RCC, and hitherto not
reported in thyroid carcinomas. CISH of both tumours revealed monosomy 3,
indicating a cytogenetical correlation between them. There was no evidence of
typical chromosomal aberrations for thyroid carcinomas like structural changes on
10q, structural rearrangements or translocations of chromosome 7. CONCLUSION:
Although neither histological sections, nor paraffin blocks of the original
nephrectomy specimen were available for review, the original tumour was on record
as clear cell RCC. Therefore the two tumours' renal origin was confirmed.
PMID- 9639120
TI - Clear cell carcinoma of the pancreas: an adenocarcinoma with ductal phenotype.
AB - AIMS: Primary clear cell carcinoma of the pancreas resembling metastatic renal
carcinoma has only rarely been described. To date it has been poorly
characterized as a distinct tumour entity. METHODS AND RESULTS: We report a case
of clear cell carcinoma in a 53-year-old man involving the head of the pancreas
and which had a small intraductal papillary component. The clear cell portion
comprised about 90% of the tumour mass. It showed predominantly a solid growth
pattern with a few scattered tubular structures. Immunocytochemically the tumour
cells stained positively for cytokeratins 7, 8, 18 and 19, whereas the reaction
for vimentin and neuroendocrine markers was negative. K-ras analysis revealed a
point mutation at codon 12 with mutation of GGT to GAT. CONCLUSION: The
intraductal tumour component of this clear cell carcinoma as well as the
cytokeratin pattern and the K-ras mutation suggest that this rare type of
pancreatic cancer has a ductal phenotype.
PMID- 9639121
TI - Intrahepatic bile duct loss in primary sclerosing cholangitis: a quantitative
study.
AB - AIMS: Intrahepatic bile duct volume density has been evaluated in four cases of
primary sclerosing cholangitis (PSC) by applying a semiautomatic image analysis
system to histological sections of surgical biopsies. Comparison was made between
normal livers and cases of primary biliary cirrhosis. METHODS AND RESULTS: A
marked decrease in both bile duct volume density in liver (up to 50% of normal
value) and bile duct volume density in portal tracts (up to 21% of normal value)
was found. The analysis of correlations between the portal tract size and the
portal tract volume fraction constituted by bile ducts confirms that the
destruction mainly affects small and medium-sized ducts. The ratio of bile duct
to arterial component volume fractions in portal tracts turned out to be inverted
with respect to that determined in normal liver, showing a decrease of up to 30%
of normal value. CONCLUSIONS: The features observed in primary sclerosing
cholangitis, as well as the extent of bile duct loss proved to be quite similar
to what we had previously described in primary biliary cirrhosis. Thus,
regardless of the causes and mechanisms leading to the bile duct loss, the
quantification of ductopenia produced results which are alike for the two
distinct cholestatic diseases.
PMID- 9639122
TI - Liver biopsy is a useful predictor of response to interferon therapy in chronic
hepatitis C.
AB - AIM: To evaluate the usefulness of easily assessable morphological parameters in
liver biopsies in order to predict efficacy of interferon-alpha (IFN) treatment
in patients with chronic hepatitis C. METHODS AND RESULTS: Inflammatory activity
and fibrosis (according to Scheuer), and the hepatic iron content (according to
Rowe and DiBisceglie) were assessed in pre-treatment liver biopsies of 73 de novo
patients with chronic hepatitis C. Furthermore the presence of fat, lymphoid
aggregates, and bile duct lesions was evaluated. With respect to IFN therapy
patients were classified as responders alanine aminotransferase (ALT) normal and
negative hepatitis C virus (HCV) RNA in serum at the end of treatment, n = 33) or
non-responders (n = 40). Non-responders had more advanced fibrosis (P = 0.0001)
and more extensive iron storage (P = 0.0008) than responders. In contrast absence
of stainable iron was frequently (46%) associated with sustained response.
Absence of fat droplets in hepatocytes was associated with response (P = 0.0001).
Stepwise logistic regression analysis indicated that the stage of fibrosis, the
hepatic iron grade, and the presence or absence of fat were independent
predictors of response. CONCLUSIONS: Liver biopsy provides useful information for
selection of patients with hepatitis C for IFN therapy.
PMID- 9639123
TI - A comparative evaluation of immunohistochemical markers for the differential
diagnosis of malignant pleural tumours.
AB - AIMS: To determine the value of immunocytochemistry in differentiation of
malignant pleural mesothelioma from carcinoma in a pleural biopsy using
commercially available monoclonal antibodies. METHODS AND RESULTS: A panel of
monoclonal antibodies against keratins, epithelial membrane antigen (EMA),
epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated
glycoprotein (B72.3), Leu-M1, CD30 (Ber-H2), vimentin and desmin, was applied to
40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic
to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber-EP4,
CEA, B72.3 and Leu-M1 were found to have the highest nosologic sensitivities
(87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%,
100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the
highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive
staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas.
Diagnostic sensitivity and diagnostic specificity (P-values) were calculated for
these markers. In respect to the diagnostic power defined by the clinically
relevant predictive values of positive and negative tests, we found that a two
marker panel of antibodies including vimentin and Ber-EP4 is most useful for the
histopathological distinction between carcinoma (pulmonary or extrapulmonary) and
malignant pleural mesothelioma. CONCLUSIONS: A combination of Ber-EP4 and
vimentin provides the most sensitive and specific pair of markers for
distinguishing between malignant pleural mesothelioma and carcinoma metastatic to
the pleura. The prevalence of the tested tumours should be taken into account
when evaluating the clinical value of ancillary techniques in pathology.
PMID- 9639124
TI - Epithelioid haemangioendothelioma of the thyroid gland: a case report and review
of literature.
AB - AIMS: This is a hitherto unreported case of an epithelioid haemangioendothelioma
of the thyroid gland. METHODS AND RESULTS: The patient was a 44-year-old woman
who presented with a right thyroid mass. A right subtotal thyroidectomy was
performed. Histologically the lesion had characteristic epithelioid and spindle
cell proliferation in a background of chondromyxoid stroma. Cytoplasmic
vacuolization in the epithelioid and spindle cells was present. No atypical
mitotic activity or necrosis was noted. The tumour cells were positive for factor
VIII-related antigen, Ulex europeus and CD 31 and were negative for cytokeratin.
CONCLUSION: The patient has been followed for 24 months and is free of recurrent
and metastatic disease, which is supportive of a benign course in the thyroid
gland.
PMID- 9639125
TI - Primary primitive neuroectodermal tumour of the urinary bladder.
PMID- 9639126
TI - Prostate-specific antigen and the salivary gland.
PMID- 9639127
TI - Squamoid eccrine ductal carcinoma.
PMID- 9639128
TI - Proteinaceous deposits and lipidic histiocytosis in follicular lymphoma.
PMID- 9639129
TI - An unusual granulomatous form of chronic pyelonephritis mimicking tuberculosis.
PMID- 9639130
TI - Large cell carcinoma of lung with osteoclast-like giant cells.
PMID- 9639131
TI - The double muscularis mucosa in ulcerative colitis: is it all new?
PMID- 9639132
TI - Outcomes research and cost-effectiveness analysis in radiology.
PMID- 9639133
TI - Receiver operating characteristic (ROC) analysis: basic principles and
applications in radiology.
AB - Receiver operating characteristic (ROC) analysis is a widely accepted method for
analyzing and comparing the diagnostic accuracy of radiological tests. In this
paper we will explain the basic principles underlying ROC analysis and provide
practical information on the use and interpretation of ROC curves. The major
applications of ROC analysis will be discussed and their limitations will be
addressed.
PMID- 9639134
TI - The cost-effectiveness of the diagnosis of renal artery stenosis.
AB - The objective of this study was to assess the cost effectiveness of eight
strategies to diagnose renovascular hypertension (RVHT) followed by treatment
with percutaneous transluminal angioplasty (PTRA) with or without stent
placement. The eight diagnostic strategies were compared with a reference
strategy, i.e. antihypertensive medication. The diagnostic imaging techniques
under consideration were captopril renography, spiral computed tomography
angiography (CTA), magnetic resonance angiography (MRA) and conventional
angiography. Cost-effectiveness analysis was carried out from the perspective of
the health care system, based on data from the literature. A model was developed
to predict the reduction in 10-year morbidity and 10-year mortality owing to
myocardial infarction, stroke and chronic renal failure achieved after PTRA
compared with the reference strategy. Life-years gained over a 10-year follow-up
period and the incremental cost-effectiveness ratio per life-year saved were the
outcome measures. The strategy CTA followed by angiography was more effective,
but more costly, than captopril renography followed by angiography, with an
incremental cost-effectiveness ratio per life-year gained of Dfl 64700. Combining
captopril renography with CTA was even more effective, but the incremental cost
effectiveness ratio per life-year gained was Dfl 236400. Strategies including MRA
were not cost-effective. The results suggest that diagnostic strategies that
include CTA are more effective than captopril renography in detecting renal
artery stenosis (> 50%) and cost saving due to prevented myocardial infarction,
stroke or chronic renal failure. MRA is even more effective, but in order to
achieve an acceptable cost-effectiveness ratio, the costs would need to be
reduced. The cost-effectiveness of the diagnostic strategies is sensitive to the
pre-test probability of RVHT. So, careful clinical evaluation, in order to
achieve a pre-test probability of at least 20%, is an essential component of the
complete workup strategy in patients suspected to have RVHT.
PMID- 9639135
TI - Clinical trials: study design and analysis.
AB - To enable doctors to select the best therapeutic strategy, the value of the
various options needs to be determined. The best approach to the evaluation of
therapeutic effectiveness and side effects is a randomised clinical trial.
Traditionally, such trials have been mainly conducted to evaluate new drugs.
However, other medical interventions, such as surgical and radiological
procedures and lifestyle changes, also require methodologically sound evaluation.
In this article, some of the basic principles of the study design of randomised
clinical trials will be discussed, such as study group comparability, treatment,
data collection and statistical analysis, as well as issues relating to
randomisation, outcome and blinding. Attention is also paid to some of the
ethical aspects.
PMID- 9639136
TI - Advances in radiology and the real versus apparent effects of early diagnosis.
AB - Over the last two decades, technological advances in radiology have
revolutionized the practice of medicine. Although the potential benefits of these
advances are well recognized, the potential harms are not. This paper describes
how early diagnosis can cause overestimations of disease prevalence and the
effectiveness of intervention. The paper begins by demonstrating how the observed
prevalence of disease increases with the sensitivity of the test and by
explaining the concept of pseudodisease. Next, the paper explains how lead time
bias, length bias and overdiagnosis bias cause overestimations of the
effectiveness of earlier diagnosis and associated treatments. These biases
pertain to both the detection and staging of disease. In addition, the paper
explains how these overestimations of disease prevalence and the effectiveness of
intervention can initiate a cycle of increasing testing and treatment, which may
eventually cause more harm than benefit. Finally, randomized clinical trials and
decision analysis are discussed in the context of evaluating new testing
strategies.
PMID- 9639137
TI - Economic analyses of radiological procedures: a methodological evaluation of the
medical literature.
AB - OBJECTIVE: Increasing pressure to curb health care costs has led to considerable
interest in economic analyses, including both cost-effectiveness and cost-benefit
analyses. Numerous economic analyses of radiological procedures have appeared in
both the radiology and non-radiology literature. The objective of this study was
to evaluate the methodological quality of economic analyses of radiological
procedures published in the non-radiology medical literature during the years
1990 1995. METHODS: Original investigations from the medical (non-radiological)
literature that include economic analyses of radiological interventions were
identified from a computerized literature search. Each economic analysis article
was evaluated by two independent reviewers for adherence to ten methodological
criteria. The criteria were derived from review of the medical and radiological
economic analysis methodology literature and consisted of the following: (1)
Comparative options stated; (2) perspective of analysis defined; (3) outcome
measure identified; (4) cost data included; (5) source of cost data stated; (6)
long term costs included; (7) discounting employed; (8) summary measure provided;
(9) incremental computation method used; and (10) sensitivity analysis performed.
The results were compared to a previous study that evaluated the radiological
literature. RESULTS: Of the 56 articles in the medical literature that included
economic analyses of radiological procedures, only eight (14%) conformed to all
ten methodological criteria. The cost data (98%) and comparative options (89%)
criteria exhibited high compliance, while the perspective of analysis (25%) and
discounting (32%) criteria had relatively low compliance. Agreement between the
reviewers was excellent (kappa = 0.88). CONCLUSIONS: Published economic analyses
of radiology procedures usually do not meet accepted methodological standards.
PMID- 9639138
TI - Meta analysis of the relationship between tuberous sclerosis complex and renal
cell carcinoma.
AB - The association of angiomyolipoma with tuberous sclerosis complex (TSC) patients
is well recognised. Some literature has suggested that patients with TSC are at
increased risk of renal neoplasm, particularly since angiomyolipomas can be
locally invasive and demonstrate tumor like neovascularity on angiography. In an
attempt to place in context one case of metastatic renal cell carcinoma in a
patient with TSC a meta analysis of the literature was performed. One pediatric
patient with TSC and metastatic renal cell carcinoma was evaluated. Reviews and
case reports of TSC and renal cell carcinoma and related imaging findings were
identified by searching the MEDLINE database, the 'bibliography of reviews' in
Index Medicus, personal files and the reference lists from all identified
reviews. Individual cases suitable for review in the available literature from
1922 through 1993 comprised the data base. The data base was analysed with the
method of proportions and unpaired two-tailed Student's t-test for different
populations. A cumulative summary of the literature amassed 107 additional cases
from 62 reports over 71 years. Our case is the 17th case, to our knowledge, of
renal cell carcinoma in TSC. Analysis of the distribution of characteristics and
incidence of; renal cysts, renal cell carcinoma, and lymph node involvement
demonstrate no increased risk of renal cell carcinoma in patients with TSC (P =
NS). Though anecdotal evidence has suggested a relationship between TSC and renal
cell carcinoma, meta analysis of cases of coincident TSC renal complex, cystic
changes, angiomyolipoma and renal cell carcinoma implies an identical, though
small, risk of malignancy in TSC patients as compared with the normal population.
PMID- 9639139
TI - Minor cerebral alterations observed by magnetic resonance imaging in syndromic
children with mental retardation.
AB - OBJECTIVE: To evaluate the anomalies of the central nervous system (CNS) by
magnetic resonance imaging (MRI) in normal subjects and in syndromic patients.
METHODS AND MATERIAL: Seventy-three normal subjects and 50 different syndromic
patients with mental retardation (from 3 months to 16 years) were studied
utilizing several morphometric parameters (degree of myelination of the white
matter, evaluation of liquoral spaces, septo-caudate distance, Evans index,
Aboulezz method, and length, width and angles of corpus callosum). RESULTS: A
high frequency of anomalies of the corpus callosum, the Chiari anomaly and
alterations either of the white matter or of the ventricular and periencephalic
system have been observed. CONCLUSION: The authors point out the importance of
cerebral MRI in the study of CNS in patients with malformation syndromes. The
present research, carried out on a large number of both normal subjects and
patients with malformation syndromes, represents one of the first systematic
studies in this field.
PMID- 9639140
TI - Cutis verticis gyrata: its computed tomographic demonstration in acromegaly.
AB - A retrospective review of the 17 cases of acromegaly, recorded in the hospital
and with available CT scans was undertaken in order to determine the presence and
of cutis verticis gyrata (CVG) frequency, and the spectrum of other associated
radiographic appearances of CVG. The hormone levels were analysed, and the
histopathology of the surgical specimens reviewed. Five cases were uncovered. In
these, the scalp in CVG was markedly thickened with convoluted, gyriform or cog
wheel appearances. There was no correlation in the age, sex, duration of symptoms
or the hormone levels in these two groups of acromegalics: with or without CVG.
All cases were histologically pituitary adenoma. It is concluded that CVG is not
uncommon in acromegaly. Its presence on a CT scan should caution the radiologist
to the presence of pituitary adenoma or any of the other neurological causes of
CVG.
PMID- 9639141
TI - Oesophageal narrowing in chronic granulomatous disease.
AB - A 14 year-old boy with X-linked chronic granulomatous disease (CGD) developed a
long smooth narrowing at the mid oesophagus with severe dysphagia. Endoscopy
revealed a normal mucosa and biopsy showed non-specific acute inflammatory
changes. Bacterial cultures of the biopsy specimens were sterile. Combined
treatment with antibiotics and steroids resulted in a transitory remission, but
symptoms recurred after 2.5 months. One second course of steroids and antibiotics
lead to a long-term remission. Oesophagogram was more useful than endoscopy to
evaluate the severity of the stricture.
PMID- 9639142
TI - MR imaging of meniscal tears with discoid lateral meniscus.
AB - OBJECTIVE: To study MR findings of meniscal tears with discoid lateral menisci
(DLMs) and to evaluate the incidence and accuracy of MRI compared to
arthroscopical surgery. MATERIAL AND METHODS: MR appearances of surgically proved
torn discoid lateral menisci (DLM) were studied in 57 knees (40 patients). They
were all performed with a 1.5T MR before surgery. MR sequences included T1- and
T2* weighted images on both coronal and sagittal planes and 3D-axial images with
a slice thickness of 0.7 mm. RESULT: Of 57 DLMs, there were 32 complete DLMs and
25 incomplete DLMs. Twenty-five of 32 complete DLMs had tears; including seven
with intrasubstance tear, five with radial tear, five with other kinds of tears
and eight with severe tears involving whole meniscus. On the other hand, 13 of 25
incomplete DLMs had tears; including two with intrasubstance tear, six with
radial tear, four with other kinds of tears and one with severe tears. All DLMs
were correctly diagnosed on MR images. Twenty-seven of 38 tears with DLM were
correctly identified on conventional 2D MR images. This yielded 71.1%
sensitivity, 100% specificity and 80.7% overall accuracy. When adding axial 3D MR
images to 2D MR images, 36 of 38 tears were correctly diagnosed. A combination of
both techniques yielded a sensitivity of 94.7% and a specificity of 100%. Ten of
11 radial tears with DLM were correctly identified on 3D axial images, where only
three of them could be diagnosed on conventional 2D images. Eight of nine
intrasubstance tears were correctly identified on 3D axial images, where six of
them could be diagnosed on conventional 2D images. CONCLUSION: DLMs had a much
higher incidence of meniscal tears than normally shaped lateral menisci and MR is
the only modality of choice to evaluate them before surgery. Especially 3D axial
MR images were quite useful in the detection of intrasubstance and radial tears
often associated with DLMs.
PMID- 9639143
TI - Intramuscular low flow vascular malformations: treatment by means of direct
percutaneous embolization.
AB - PURPOSE: Intramuscular hemodynamically inactive vascular malformations are
infrequent entities whose surgical treatment is often impossible, crippling, or
inefficient. We describe a nonsurgical therapeutic approach consisting on
embolization by direct puncture with sclerosant substances. METHODS: Four
patients have been treated from April to November 1994, three female and one
male, ranging in age from 13 to 31 years. Three vascular malformations were
located in the quadriceps and one in the deltoid muscle. The point of access was
determined with information provided by MR. The skin was cleaned with an
antiseptic solution and puncture was performed with a 22 gauge Chiva needle.
Blood flow inside the malformation was slow in all cases and no afference to the
normal venous system was detected. We embolized with 5-15 cc (mean 7.5 cc) of a
mixture of ethibloc and ethanol. RESULTS: The mean follow-up period was 17 months
(range 14-21). All patients remain asymptomatic and have resumed normal daily
life activities. There were no complications. CONCLUSION: Percutaneous
embolization by direct puncture of intramuscular vascular malformations is a
feasible and simple procedure. Our preliminary results are promising, although
more extensive studies need to be to performed in order to reach definite
conclusions.
PMID- 9639144
TI - A validation of a flow quantification by MR phase mapping software.
AB - AIM: We evaluated a Siemens software of flow quantification (FQ) by MR phase
mapping, in the framework of a common practical use. METHODS: Experiments with a
laminar flow phantom and in vivo pulsatile flow were performed. In particular, FQ
in ascending aorta was investigated in healthy volunteers. RESULTS AND
CONCLUSION: Flow phantom experiments reveal that the FQ slightly underestimates
(8% on the average) actual velocities (mean velocities over a vessel area), and
also that velocity uncertainties are related to the encoding velocity value,
whatever the measured velocity. Furthermore, using well characterized working
criteria, we found low intraobserver variability and negligible interobserver
variability in ascending aorta FQs. The role played by the choice of reference
area in FQ accuracy is emphasized. When recording several cardiac cycles during
the same acquisition, it is shown that the FQ software may provide erroneous
results. Several comments for FQ software use in the ascending aorta are added.
PMID- 9639145
TI - Gossypol as a male antifertility agent--why studies should have been continued.
AB - It has been nearly three decades since the beginning of nationwide research into
gossypol as a male antifertility agent in China. Several lines of data
implicating some side effects of gossypol were published which led to the
termination of this area of research in China. The present review re-examines
these data and points out the confusion surrounding issues such as hypokalaemia,
irreversible azoospermia and other side effects. The prospects and related
difficulties for gossypol as a potential male contraceptive are also discussed.
PMID- 9639146
TI - Gossypol: reasons for its failure to be accepted as a safe, reversible male
antifertility drug.
AB - Following clinical trials conducted in China in the 1970s, gossypol was proposed
as a drug for male contraceptive use. This review summarizes the extensive
investigations on formal animal toxicology and on the recovery of fertility in
men after stopping gossypol treatment which led to the decision by the Special
Programme of Research, Development and Research Training in Human Reproduction
(HRP) at the World Health Organization (WHO), that gossypol would not be
acceptable as an antifertility drug. It is concluded that the assessment of
gossypol reinforces the mandatory requirement that future contraceptive drugs
must be developed by the established routes of appropriate animal toxicology and
phased clinical studies.
PMID- 9639147
TI - Centromere sequences localize to the nuclear halo of human spermatozoa.
AB - Chromatin is organized into a series of discrete nuclear matrix-associated and
non-nuclear matrix-associated domains. The non-matrix-associated domains consist
of loops of DNA that are attached to the proteinaceous nuclear matrix by matrix
associated regions (MARs). Although this organization is well characterized in
somatic cells, comparatively little is known of this mode of organizing the
genome in the human sperm nucleus. To define this relationship, the interaction
of human sperm chromatin with the nuclear matrix was assessed by fluorescence in
situ hybridization using specific alpha satellite probes directed to the
centromeric regions of chromosomes 13 plus 21 and 18. Hybridization of the
centromeric sequences was visualized as segmented, bundled structures that
extended from the nuclear core into the halo.
PMID- 9639148
TI - Binding of seminal vesicle proteins to the plasma membrane of rat spermatozoa in
vivo and in vitro.
AB - The association of seminal vesicle (SV) proteins with rat spermatozoa has been
studied in vivo and in vitro. SV proteins bind to the sperm plasma membrane after
ejaculation but are removed progressively from the sperm plasma membrane in the
female genital tract. Although some of these remain bound to spermatozoa when
they reach the oviducts, they do not seem to be present at the time of
fertilization. This could indicate a putative role for these SV proteins in pre
fertilization events. In addition, the binding of SV antigens was studied in
vitro. It was observed that the ability to bind SV proteins is gained by the
spermatozoa during epididymal maturation, and is first detectable in spermatozoa
collected from the cauda epididymis. On the other hand, the binding is regulated
by other proteins present in the ejaculate which are secreted by the coagulating
glands. Experiments also showed that mouse spermatozoa are able to bind rat SV
proteins, indicating that the binding is not a highly species-specific
phenomenon.
PMID- 9639149
TI - Effects of nitrogenous components of urine on sperm motility: an in vitro study.
AB - The effects of the major nitrogenous components of urine (ammonia, creatinine,
urea and uric acid) on sperm motility were investigated. Semen samples were
obtained by masturbation from a young volunteer with a normal spermiogram and
fertility. Sperm motility was measured using a Sperm Quality Analyzer and Makler
Chamber. When semen was mixed with a urine sample for which acidity and
osmolality were adjusted to pH 7.5 and 340 mOsm/kg, the higher the concentration
of the urine, the poorer the sperm motility. When solutions of various
concentrations of the nitrogenous compounds which are excreted in urine were
mixed with semen, sperm motility decreased in proportion to ammonia levels and
was markedly decreased after 30 min. However, in the case of creatinine, urea and
uric acid, good motility was maintained for 30 min regardless of their amounts.
In conclusion, urine ammonia content is detrimental to sperm motility and may be
an important factor in retrograde ejaculation.
PMID- 9639151
TI - Performance of the sperm quality analyser in predicting the outcome of assisted
reproduction.
AB - The present study was undertaken to assess the relationship between the results
of conventional semen analysis and the sperm motility index (SMI) as measured by
the sperm quality analyser (SQA), and to evaluate these in relation to the
fertilization and/or pregnancy outcome of assisted reproduction. SMI
determinations and conventional semen analyses were performed on 223 samples from
subfertile men in two laboratories in Leuven (n = 136) and Antwerp (n = 87), and
on spermatozoa prepared on a Percoll gradient (n = 136) used for treatment of
male factor infertility in 57 cycles of intrauterine insemination (IUI), 44
attempts at in vitro fertilization (IVF) and 31 attempts at intracytoplasmic
sperm injection (ICSI). SMI values for native semen correlated significantly with
sperm concentration, motility and morphology. Multiple regression analysis
revealed sperm concentration after preparation, and the concentration of motile
spermatozoa with normal morphology and SMI (before preparation) to be the
independent determinants for SMI after preparation. SMI values were significantly
higher after, than before, preparation (p < 0.0001). In regular IVF (n = 44) the
percentage of fertilized oocytes correlated significantly (p < 0.05) with sperm
motility (A + B%, r = 0.33), with the percentage of spermatozoa with normal
morphology (r = 0.46) before preparation, with the values of SMI both before and
after preparation (r = 0.54, r = 0.48), with sperm concentration (r = 0.34) and
with the motile sperm concentration (r = 0.29) after preparation. For the
occurrence of pregnancy (all treatment methods), comparison of areas under ROC
curves (AURC) indicated motile sperm concentration after preparation, as well as
SMI both before and after preparation, to have the highest AURC, with no
significant difference between these values as far as predictive power was
concerned. These results indicate that the SQA allows for rapid evaluation of
sperm characteristics and of the effectiveness of sperm preparation techniques.
However, it is not superior to conventional semen analysis in predicting the
outcome of assisted reproduction.
PMID- 9639150
TI - Characterization and expression of a stage specific antigen by monoclonal
antibody TRA 54 in testicular germ cells.
AB - To study the mechanism of spermatogenesis, we have isolated many monoclonal
antibodies (mAb) which recognize specific steps of mouse germ cell
differentiation and then have evaluated the specific expression and
characterization of antigenic molecules using immunohistochemistry and Western
blotting. Monoclonal antibody TRA 54 recognized specific organelles in germ cell
cytoplasm from spermatocytes to spermatids; that is, a large granule was stained
in mid-late pachytene, diplotene and secondary spermatocytes and in round
spermatids at stage I while the acrosome of spermatids at steps 2-3 to step 12
were also positive. Thereafter, the antigens disappeared from spermatids at more
advanced stages of differentiation. Western blots using TRA 54 revealed broad
bands with approximate molecular weights of >200, 190 and 85 kDa in the testis.
The expression of these antigens during testicular germ cell development should
be of interest in relation to the biogenesis of organelles such as the chromatoid
body and acrosome and will be a useful stage-specific molecular marker for the
study of spermatogenesis.
PMID- 9639152
TI - Semen levels of mitochondrial DNA deletions in men attending an infertility
clinic do not correlate with phenotype.
AB - In view of previous reports associating mitochondrial DNA deletions with male
reproductive disorders, levels of the 'common' 4977 bp mitochondrial DNA deletion
were evaluated semi-quantitatively in 64 men, without prior knowledge of the
clinical diagnosis. Significant levels of deletions were detected in 34/64 men
(53%) but 29 of these (45%) had a normal semen profile and were phenotypically
normal. No deletions were detected in 30 men, of whom 21 were normospermic, six
were oligozoospermic and three were azoospermic. It is concluded that although
mitochondrial DNA deletions within the testis may be associated with primary
testicular disease, no correlation with semen quality was evident in this study,
thus limiting its potential use as a diagnostic test.
PMID- 9639153
TI - Asymmetrical testicular weights in mammals, birds, reptiles and amphibia.
AB - The testes of different classes of animals (mammals, birds, reptiles and
amphibia) were weighed. Some species showed inconsistent left-right asymmetric
testicular weights, while other species (including amphibians, reptiles, some
birds and some mammals) showed consistent asymmetry in their weights. In rodents,
for example, five strains of mice consistently exhibited asymmetrical testes,
with the right testis always being heavier than the left. In contrast, another
strain of mice showed inconsistent bilateral asymmetry of the testes.
PMID- 9639154
TI - Validation of a recording protocol for assessing temporomandibular sounds and a
method for assessing jaw position.
AB - Sounds are often produced by the temporomandibular joint (TMJ) during movement in
both symptomatic and asymptomatic subjects. However, subjective methods of
describing these sounds have been shown to have poor inter- and intra-observer
reliability. In this study, a low cost system in which TMJ sounds were detected
using the loudspeakers of lightweight in-ear headphones as microphones is
evaluated. The sounds were recorded on tape and then analysed using a computer.
Sounds were elicited by asking subjects to bring their teeth together with
sufficient force to produce a tooth contact sound, then open their mouths as far
as possible and then close again. Placing the microphones in the ears attenuated
ambient sounds by 58%, thus providing a degree of immunity from ambient noise.
Sampling was performed on the left microphone only at 3.4 kHz and from the left
and right microphones together at 1.7 kHz for 60 TMJ sounds and 60 tooth contact
sounds. Spectral analysis of sounds recorded at the two sample rates revealed no
significant differences. Therefore, a sample rate of 1.7 kHz is adequate to
resolve the frequency components present in the TMJ sounds. Although simply
recording TMJ sounds does not give a direct measurement of the position of the
mandible, using this protocol allows the length of the open close cycle to be
determined. If the envelope of movement is assumed to approximate a sinusoid,
then the direction of mandibular movement can be assumed to reverse at the half
way point in the cycle. The accuracy of this assumption was calculated by
comparing the mid-point of the cycle to the point of maximum gape in 129 cycles
from nine subjects. The mean difference expressed as percentage of cycle length
was 1.3 +/- 0.9%.
PMID- 9639155
TI - Two-dimensional configuration of the myoneural junctions of human masticatory
muscle detected with matrix electrode.
AB - Motor unit action potentials (MUAPs) propagate bidirectionally from the myoneural
junction along the muscle fibre. The propagation of excitation within single
motor units can be detected during sustained isometric contraction using a
surface electrode array. Electromyographic (EMG) signals from an adjacent pair of
contacts along the muscle fibres show a very similar wave form with a time shift.
In the present study, EMG signals of the masseter and the temporal muscles were
obtained from two male adults during clenching in the intercuspal position using
the multichannel surface electrode with 17 x 11 contacts. The two-dimensional
location of the myoneural junction for each column from the source of the
propagation was estimated. Each of the myoneural junctions was located in the
lower portion of the masseter muscle and in the upper portion of the temporal
muscle. However, the junction was distributed within 10 mm along the muscle
fibres at different contraction levels in each muscle. This noninvasive technique
of multiple surface electrodes enabled us to add to knowledge of the anatomical
structure of the masticatory muscles examined.
PMID- 9639156
TI - A comparison between the wear resistance of three types of denture resin to three
different dentifrices.
AB - This study compares the abrasive effects of three dentifrices on three different
denture base resins, a heat cured acrylic resin, a self cured acrylic resin and a
light activated urethane dimethacrylate-based resin. Specimens of the resins were
subjected to a regimen of mechanical brushing using measured amounts of paste on
standard toothbrushes driven by a reciprocating device. The apparent wear of each
specimen was assessed qualitatively using scanning electron microscopy and
quantitatively using profilometry and reflex microscopy. The study showed that
cleaning pastes play a significant role in the wear of conventional acrylic
resins, the relative abrasivity of the dentifrices being substrate related.
However, wear was less evident on the light activated urethane dimethacrylate
resin. Brushing with water alone produced no detectable wear on any of the
specimens.
PMID- 9639157
TI - Cerana--a new method for the restoration of teeth with prefabricated ceramic
inlays.
AB - Cerana are all-ceramic, prefabricated inlays which replace enamel and are
produced in a lucite-reinforced glass ceramic. To evaluate the clinical quality
of Cerana inlay therapy, 38 patients with a total of 60 inlays were examined in a
retrospective cross-sectional study. The inlays were primarily of Class I type,
but even Class II tunnel preparations and Class V were examined. The median age
of the inlays was 1.5 years. A modified form of the California Dental Association
criteria was used in the evaluation. The results show that all inlays were of
excellent or acceptable character in terms of marginal fit, colour and surface
roughness. None of the patients reported any post-operative symptoms of pain. One
restoration had secondary caries and a fractured marginal ridge. One restoration
with poor anatomical form caused by a fractured filling and one restoration with
deep marginal discolouration were discovered. Although the follow-up time was
short, the results show that Cerana can be considered an interesting alternative
to other tooth-coloured materials on the market.
PMID- 9639158
TI - Curing depth of four composite veneering materials polymerized with different
laboratory photo-curing units.
AB - Post-curing properties of composite materials are influenced by the type of base
monomer, activation system, filler content, and also by the type of light source
employed. This study examined curing depth of four composite veneering materials
polymerized by means of two different high-intensity photo-curing units for the
purpose of evaluating the curing performance of the combinations of composite
material and photo-curing unit. Two microfilled and two hybrid composite
materials designed for prosthetic veneer were assessed. The composite materials
were cured using two photo-curing units, one with a xenon light source and one
with two metal halide light sources, and exposure periods varied from 20 to 90 s.
Curing depth of the materials was determined with a scraping technique described
by the International Organization for Standardization (ISO 4049). Three-factor
analysis of variance revealed that the depth of cure was influenced by the type
of composite material as well as by the photo-curing unit, and also by the
exposure period (P = 0.0001). A microfilled composite material (Dentacolor)
demonstrated the greatest depth of cure (4.69 mm) after 90 s irradiation with a
metal halide unit (Hyper LII). Of the two photo-curing units, the metal halide
curing unit consistently exhibited greater depth of cure than the xenon curing
unit (Dentacolor XS). Longer exposure increased the depth of cure for all
combinations.
PMID- 9639159
TI - Ratio between vertical and horizontal mandibular range of motion.
AB - Mandibular range of motion (ROM), vertical and horizontal, is often measured as a
part of a diagnostic assessment of temporomandibular joint disorders. In the
literature, a fixed ratio between the vertical and the horizontal ROM has been
suggested, i.e. 4:1. The ratio is frequently used to predict the vertical ROM on
the basis of the horizontal ROM and vice versa. However, no scientific data are
available to substantiate the ratio suggested. The aim of this study was to
determine whether the fixed ratio of 4:1 exists and, if so, whether this ratio
has a predictive value. Vertical and horizontal mandibular ROM was measured in 91
healthy subjects, 59 women, and 32 men (mean age 27.2 years, s.d. 7.4 years)
using vernier callipers. We found a mean ratio between vertical and horizontal
ROM ranging from 6.0:1-6.6:1. On an individual basis the ratio ranged from 3.6
15.5. Correlations between vertical and horizontal ROM were weak. On the basis of
the results on this study it is concluded that the ratio between vertical and
horizontal ROM is approximately 6:1 rather than 4:1, and that the ratio has poor
predictive value.
PMID- 9639160
TI - Properties of four composite veneering materials polymerized with different
laboratory photo-curing units.
AB - This study examined properties of four composite veneering materials polymerized
with two different photo-curing units for the purpose of evaluating curing
performance of the combination of composite material and curing unit. Two
microfilled (Dentacolor and Thermoresin LC II) and two hybrid (Cesead II and
Solidex) composite materials designed for prosthetic veneer were selected. The
respective light sources of the units were a xenon (Dentacolor XS) and a metal
halide (Hyper L II) lamp. The composite materials were exposed with the photo
curing unit for 60 s on each side (i.e. from top and bottom). Knoop hardness,
compressive strength, flexural strength, flexural modulus, water absorption and
water solubility were determined according to standardized testing methods. The
specimens exposed with the metal halide unit generally exhibited greater Knoop
hardness number, and compressive strength and lower solubility than those exposed
with the xenon unit. A microfilled material (Thermoresin LC II) cured with the
metal halide unit exhibited significantly improved results for all tests as
compared with the same material cured with the xenon unit.
PMID- 9639161
TI - Detection of onset and termination of muscle activity in surface electromyograms.
AB - A method of automated detection of onset and termination of rhythmic muscle
activity in electromyograms (EMGs) is presented. A threshold level in the EMG is
computed, such that amplitudes in the EMG signal exceeding this level indicate
muscle activity. The threshold level is determined using a statistical criterion
based on the amplitude distribution of the entire EMG signal. The working of the
method is illustrated with EMG signals recorded from chewing muscles. EMG signals
with a good as well as a worse signal-to-noise ratio are presented. The method
can be used for any EMG signal containing cyclic bursts of activity and thus may
be applied in studies on rhythmic movements, such as chewing, walking and
breathing. An automated method of EMG burst detection has the advantage that
large amounts of EMG data can be easily and objectively processed.
PMID- 9639162
TI - Comparison of the most comfortable mandibular position with the intercuspal
position using cephalometric analysis.
AB - For evaluation of the most comfortable position (MCP) in edentulous subjects, as
decided by mandibular position sense, the MCP was recorded in ten edentulous
subjects and compared with the intercuspal position (ICP) of normal dentate
persons. It was found that the MCP was at a lower mandibular position than the
ICP; the facial height was markedly reduced in the former by a front-upward
rotation of the mandible centering around the condyles. Thus, it has been
suggested that the occlusal vertical dimension (OVD) of the MCP in the restored
dentition is less than that of the original ICP.
PMID- 9639163
TI - Posterior bite collapse--revisited.
AB - Although there are different definitions of posterior bite collapse, only the
classical definition of Amsterdam provides a definite diagnosis and treatment
plan. This situation entails a subtle loss of the occlusal vertical dimension
with resultant flaring of the maxillary incisors. Other causes for flaring, such
as derangements of form and functions of lips and tongue, bruxism, habits, as
well as the presence of advanced periodontal disease or malocclusions, should be
ruled out before the diagnosis of posterior bite collapse can be made. The
complexity of differential diagnosis is illustrated with three case reports.
PMID- 9639164
TI - Examination of the diagnostic value and estimation of the chaos phenomenon in
masticatory movement using fractal dimension in patients with temporomandibular
dysfunction syndrome.
AB - The aim of this study was to estimate the chaos phenomenon (chaos) in masticatory
movements using the fractal dimension (FD), and to examine the diagnostic value
of the fractal dimension in comparing stomatognathic functional disturbances with
normal stomatognathic function. The subjects were all high school students and
included nine subjects presenting with acceptable normal occlusion, 18 subjects
with TMJ dysfunction syndrome and seven subjects with tooth crowding. Masticatory
movements were obtained during free, right side, and left side gum-chewing and
were used to calculate the capacity dimension in the FD. Chaos in the masticatory
movement was estimated by the FD saturated with some constant value to an
increase of embedding dimension (approached a plateau). In the crowding group,
the FD was also significantly high on the sagittal plane in comparison with the
normal. In the patients with pain, the FD on the sagittal plane was significantly
high. In the patients with pain and closed lock, the FD on the frontal plane was
significantly high. However, in the patients with pain and with reduction of
anterior disc displacement, the FD was significantly low on the horizontal plane.
These findings suggest that chaos is present in masticatory movements and the
difference in the FD are of diagnostic value in evaluation of the relationship
between FD and stomatognathic functional disturbance.
PMID- 9639165
TI - Monitoring the state of the occlusion--gnathosonics can be reliable.
AB - Monitoring the state of the occlusion should include records that can be
compared. Gnathosonics has not become generally accepted as an everyday method of
assessing the quality of the occlusion. It is suggested that this may be due to
inconsistencies in the results obtained by various workers in the field. It is
further suggested that such inconsistencies could be due to the manner of data
gathering in the areas of equipment, transfer of data from the patient and
interpretation of the records. A reliable method of data gathering using
accelerometers is suggested and, taking account of the complexities of sound
transmission through the skull, concludes that the overall envelope of the sounds
produced by the occlusion of the teeth is more informative that the actual
frequencies generated. Ways in which gnathosonics could be placed on a scientific
footing and areas where further investigation might be useful are suggested.
Gnathosonics, properly controlled, can provide a simple, quick and reliable
method of making permanent records of occlusal sounds for comparison and
assessment of stability or change in the state of the occlusion.
PMID- 9639166
TI - The making and the breaking of senescence: changes of gene expression during
cellular aging and immortalization.
PMID- 9639167
TI - Metabolite concentrations in skeletal muscle of different aged rats submitted to
hypoxia and pharmacological treatment with nicergoline.
AB - The energy metabolism of the gastrocnemius and soleus muscles in young-adult,
mature, and senescent rats was evaluated after 72 h of continuous exposure to
normobaric hypoxia or normoxia. The effects of treatment with the alpha
adrenergic antagonist nicergoline were also investigated. In the gastrocnemius
muscle we evaluated the concentrations of some significative metabolites involved
in anaerobic glycolysis and the Krebs' cycle, free amino acids related to the
Krebs' cycle, ammonia, some energy mediators, and the energy store creatine
phosphate. In the soleus muscle a selection of these was evaluated. In both
muscles aging was similarly characterized by a decrease in muscular creatine
phosphate concentration, while the energy mediators and the energy charge
potential remained unchanged. Singly, some gastrocnemius muscle metabolites
showed linear changes in their concentrations with aging, while for the soleus
muscle the only linear change regarded glucose-6-phosphate. Continuous normobaric
hypoxia induced greater changes at the age of 4 and 24 months than at 12 months.
Chronic treatment with nicergoline modified the influence of hypoxic conditions
on muscle metabolites concentrations only in some cases, regardless of the age of
the animals. Further investigations are necessary before any firm conclusions can
be drawn about the pharmacological activity of nicergoline on hypoxia in aged
rats.
PMID- 9639168
TI - Effect of chronic hyperoxia on young and old rat carotid body ultrastructure.
AB - Morphologic, physiological, and biochemical changes occur in the carotid body
(CB) during postnatal development in relation to physiological requirements.
Chronic normobaric hyperoxia attenuates the carotid chemosensory response to
hypoxia. During aging there is less of a CB response to hypoxia, which results in
a reduced ventilatory adaptation and chemosensory discharge. To test if the
oxygen-sensitive mechanism is affected by chronic hyperoxia in an age-dependent
fashion, we have studied structural and ultrastructural aspects of young and old
rat CBs. Four groups of six male Wistar rats were used. One group of two-month
old rats and another of 25-month-old rats were kept at room air. The other two
groups, age matched, were exposed to 98-100% O2, for 60-65 h, in a large
Plexiglas chamber. The rats were anesthetized, CBs were fixed in situ with
glutaraldehyde (2.5% in phosphate buffer. pH 7.4, 320 mOsm), and were prepared
for electron microscopy. Young hyperoxic rats showed focal necrosis in type I
cells, along with an increase of endoplasmic reticulum, Golgi apparatus, and of
mitochondria volume, with loss of cristae. These changes were less pronounced in
the older rat CBs compared with the young rats. In conclusion, hyperoxia seems to
affect the oxygen-sensitive mechanism in the carotid body cells, and the reduced
effects shown in the old rat CBs suggest an age-related decreased sensitivity to
oxygen.
PMID- 9639169
TI - Cohort size and maximum likelihood estimation of mortality parameters.
AB - The purpose of this study was to investigate the effects of cohort size on
maximum likelihood estimates of mortality parameters. Recent experimental
investigations have stressed the importance of large cohorts for detecting
leveling off of mortality rates at older ages. In the present study, emphasis was
placed on evaluation of relatively small cohorts (about 150-300 individuals).
Deaths were simulated under the assumption of the frailty mortality model. Two
different parameter sets that resulted in differences in mean life span of more
than twofold were used for simulations. Our smallest cohorts yielded parameter
estimates that had generally good statistical properties, but relatively large
standard errors. For tests of hypotheses concerning equality of parameters among
populations or experimental treatments, empirical standard errors (obtained from
several cohorts) were preferable to asymptotic standard errors (obtained for
single cohorts). In particular, empirical standard errors yielded reliable type I
error rates.
PMID- 9639171
TI - 1st meeting of the German Interest Group for Geronto-Endocrinology.
PMID- 9639170
TI - Analysis of the effect of membrane arachidonic acid concentration on modulation
of glutamate release by interleukin-1: an age-related study.
AB - Aging is associated with a change in membrane composition that includes a
decrease in membrane polyunsaturated fatty acids, including arachidonic acid, and
an increase in membrane cholesterol. Alterations in membrane structure are likely
to impact on transmitter release, which relies on the fusion of synaptic plasma
and synaptic vesicle membranes, and it may therefore be the underlying cause of
the age-related decrease in glutamate release in hippocampal preparations. Recent
evidence indicates that interleukin-1, by binding with its receptor, inhibits
glutamate release in hippocampal synaptosomes prepared from young but not aged
rats. The age-related attenuated effect may be due to impaired ligand-receptor
interactions arising from the change in membrane composition, which should
theoretically be reversed by increasing membrane polyunsaturated fatty acid
concentration. To test this hypothesis, we have investigated the effect of a diet
supplemented with arachidonic acid and its precursor, gamma-linolenic acid, on
membrane arachidonic acid concentration, glutamate release and on the release
response to interleukin-1 in hippocampal tissue prepared from aged and young
rats. We report that dietary supplementation reversed the age-related changes in
membrane arachidonic acid and expression of IL-1beta. We also present data that
indicate that the age-related decrease in glutamate release from hippocampal
synaptosomes was reversed in aged animals that had been fed on the experimental
diet. The data support the view that changes in membrane composition contribute
to certain age-related deficits, in particular the decrease in glutamate release
observed in hippocampal synaptosomes.
PMID- 9639172
TI - The clinical relevance of observational research.
PMID- 9639173
TI - Analgesia in the accident and emergency department: do SHOs have the knowledge to
provide optimal analgesia?
AB - OBJECTIVE: To assess senior house officers' knowledge in prescribing emergency
analgesia for acute presentations in the accident and emergency (A&E) department.
DESIGN: Prospective telephone survey of a defined population of SHOs, using a
standardised structured questionnaire, in the months of October and November,
1995; 231 SHOs from 215 A&E departments were interviewed. The questionnaire
required responses to hypothetical scenarios. A six member expert panel from the
local region was consulted for suggestions for appropriate responses. MAIN
OUTCOME MEASURES: Comparisons between SHO responses and those of an expert panel.
RESULTS: For choice of analgesic agent, 83% of SHO responses were appropriate,
for route of administration 57%, and for the dose of drug 34%. The scenario with
the best overall response was a sprained ankle. The paediatric case with partial
burns faired worse. Responses to a myocardial infarction scenario were the most
consistent. CONCLUSIONS: A&E SHOs lack knowledge and confidence when asked to
prescribe emergency analgesia for acute conditions. Responses to certain
scenarios were extremely varied, indicating a need for national analgesia
guidelines and protocols. Recognised training in pain management should be more
readily available.
PMID- 9639174
TI - Do supine oblique views provide better imaging of the cervicothoracic junction
than swimmer's views?
AB - OBJECTIVE: To determine whether a swimmer's view or supine (trauma) oblique views
are more likely to visualise the lower cervical spine when a lateral view fails
to show the cervicothoracic junction. DESIGN: A prospective study comparing two
20 week periods. In the first phase the swimmer's view was performed as an
additional view when the cervicothoracic junction was not demonstrated. In the
second phase paired supine oblique views replaced the swimmer's view. RESULTS:
230 patients were included in the first phase, of whom 60 required swimmer's
views. In the second phase 62 of 197 patients required supine oblique views.
Radiology analysis of 53 pairs of supine oblique views showed that the vertebral
bodies were adequately demonstrated at the cervicothoracic junction in only 20
patients (38%) compared with 22 in the swimmer's group (37%). The facet joints
and posterior elements were, however, clearly seen in 37 (70%) of the supine
oblique patients compared with 22 (37%) of the swimmer's group (p < 0.001, chi2
test). Exposure dose calculations showed a substantial reduction for a pair of
supine oblique views (1.6 mGy) over a single swimmer's view (7.2 mGy).
CONCLUSIONS: In injured patients for whom the standard three view series fails to
demonstrate the cervicothoracic junction, swimmer's views and supine oblique
views show the alignment of the vertebral bodies with equal frequency. However,
supine oblique films are safer, expose patients to less radiation, and are more
often successful in demonstrating the posterior elements.
PMID- 9639175
TI - Efficacy of transabdominal ultrasound examination in the diagnosis of early
pregnancy complications in an emergency department.
AB - OBJECTIVE: To assess the value of ultrasound in an emergency department in the
diagnosis of early pregnancy complications, the efficacy of a study protocol in
identifying ectopic pregnancies, and the agreement on ultrasound findings among
emergency department staff and gynaecologists. METHODS: All women presenting with
early pregnancy complications had a transabdominal ultrasound scan performed by
the attending doctor and checked by a senior doctor. The ultrasound findings were
classified as normal intrauterine pregnancy (IUP), probable abnormal pregnancy,
definite ectopic pregnancy, no definite IUP, and other. Women with clinical and
ultrasound findings compatible with threatened abortion were referred to a
gynaecologist, or were admitted if findings suggested abnormal or ectopic
pregnancy, or if a definite IUP could not be confirmed on ultrasound scan. For
patients who were admitted or referred, a transvaginal ultrasound scan was
performed by the attending gynaecologist. The findings of the gynaecologist were
used as the gold standard. RESULTS: 151 cases were enrolled during a four month
study period. Ultrasound findings in the emergency department included definite
IUP in 95 (63%), probable abnormal IUP in 20 (13%), no definite IUP in 23 (21%),
and other findings in four (3%). For evaluating the presence or absence of IUP,
sensitivity of the initial scan was 82% (95% confidence interval 76% to 88%) and
specificity 92% (88% to 96%). Agreement between junior and senior emergency
department doctors on their ultrasound findings was 81% (75% to 87%) and between
emergency department senior staff and gynecologists 85% (79% to 91%). The
diagnoses made in the emergency department were thought to be compatible with the
final assessments by gynaecologist in 72% (65% to 79%). Using either no definite
IUP or other findings as a positive screening test for ectopic pregnancy, the
sensitivity, specificity, positive predictive value, and negative predictive
value were 80% (74% to 86%), 78% (71% to 85%), 12% (7% to 17%), and 99% (97% to
100%), respectively. CONCLUSIONS: Transabdominal ultrasound performed in the
emergency department is useful in screening for early pregnancy complications.
Ectopic pregnancy should be suspected when no IUP is found on preliminary
scanning.
PMID- 9639176
TI - The risks of minor head injury in the warfarinised patient.
AB - The risk factors affecting intracranial haemorrhage in warfarinised patients are
described and an attempt made to calculate the risk of haemorrhage in
warfarinised patients with minor head injuries. Using the data from studies of
patients with spontaneous haemorrhage while taking warfarin, guidelines for
treatment and given and the likely outcome predicted.
PMID- 9639177
TI - Aerobic and anaerobic microbiology of infections after trauma in children.
AB - OBJECTIVE: To review the recovery of aerobic and anaerobic bacteria from
infections after trauma in children over a 20 year period. METHODS: Only
specimens that were studied for both aerobic and anaerobic bacteria were included
in the analysis. They were collected from seven separate centres in which the
microbiology laboratories only accepted specimens that were properly collected
without contamination and were submitted in appropriate transport media.
Anaerobes and aerobic bacteria were cultured and identified using standard
techniques. Clinical records were reviewed to identify post-trauma patients.
RESULTS: From 1974 to 1994, 175 specimens obtained from 166 children with trauma
showed bacterial growth. The trauma included blunt trauma (71), lacerations (48),
bites (42), and open fractures (5). Anaerobic bacteria only were isolated in 38
specimens (22%), aerobic bacteria only in 51 (29%), and mixed aerobic-anaerobic
flora in 86 (49%); 363 anaerobic (2.1/specimen) and 158 aerobic or facultative
isolates (0.9/specimen) were recovered. The predominant anaerobic bacteria
included Peptostreptococcus spp (115 isolates), Prevotella spp (68),
Fusobacterium spp (52), B fragilis group (42), and Clostridium spp (21). The
predominant aerobic bacteria included Staph aureus (51), E coli (13), Ps
aeruginosa (12), Str pyogenes (11) and Klebsiella pneumoniae (9). Principal
infections were: abscesses (52), bacteraemia (3), pulmonary infections (30,
including aspiration pneumonia, tracheostomy associated pneumonia, empyema, and
ventilator associated pneumonia), wounds (36, including cellulitis, post
traumatic wounds, decubitus ulcers, myositis, gastrostomy and tracheostomy site
wounds, and fasciitis), bites (42, including 23 animal and 19 human), peritonitis
(4), osteomyelitis (5), and sinusitis (3). Staph aureus and Str pyogenes were
isolated at all sites. However, organisms of the oropharyngeal flora predominated
in infections that originated from head and neck wounds and abscesses, and bites,
and those from the gastrointestinal tract predominated in infections that
originated from peritonitis, abdominal abscesses, and decubitus ulcers.
CONCLUSIONS: Many infections that follow trauma in children involve multiple
organisms.
PMID- 9639178
TI - Primary care problems in patients attending a semi-rural accident and emergency
unit: a prospective study.
AB - OBJECTIVE: To analyse the characteristics of patients attending a coastal resort
accident and emergency (A&E) unit and compare use by summer visitors with use by
the indigenous winter population by previously validated assessment criteria.
SETTING: Accident and emergency unit of a semi-rural coastal town district
general hospital. SUBJECTS: 3643 first attenders in the summer cohort and 2876 in
the winter cohort. METHODS: All patients attending the A&E unit over two 28 day
periods in summer and winter 1995 were assessed prospectively in four categories
by trained, experienced nurse assessors. Category 4 identified patients who
fulfilled the King's College Hospital criteria as being suitable for care from
primary care practitioners. RESULTS: 43.8% of the summer patients could have been
seen in the primary care setting, as could 38.7% of the winter visitors.
CONCLUSIONS: The proportion of patients with primary care problems who attend
semi-rural A&E units appears to be much higher than previously thought. These
findings cast doubt on the validity of the King's College Hospital criteria for
classifying patients to either primary care or A&E categories.
PMID- 9639179
TI - The work of the American emergency physician.
AB - The organisation of the American emergency health care system has changed rapidly
during recent years, but it remains very different to the system in the United
Kingdom. American emergency departments are organised around an attending
physician based service, rather than a consultant led service. As a result, the
work of the American emergency physician differs considerably from that of the
United Kingdom A&E consultant. The problems associated with working in an
attending physician based service include antisocial hours of work, sleep
deprivation, decreased job satisfaction, and "burn out," all in the context of a
relatively hostile medicolegal climate. Although there appear to be no easy
answers to some of these problems, the A&E specialist should be aware of the
potential future difficulties for A&E medicine as it develops within the United
Kingdom.
PMID- 9639180
TI - A transatlantic comparison of training in emergency medicine.
AB - The system of training in accident and emergency (A&E) medicine in the United
Kingdom is at a critical and much earlier stage of development than in the United
States. Transatlantic comparison offers the opportunity to explore possible ways
of improving training in the United Kingdom. Comparison revealed deficiencies in
the UK training system in the following: prehospital care training, formal
theoretical teaching, close supervision in a clinical setting, and in-service
training examinations. Implementation of measures designed to address these
deficiencies would enhance UK training in A&E medicine.
PMID- 9639181
TI - Accident and emergency 24 hour senior cover--a necessity or a luxury?
PMID- 9639182
TI - The flat electrocardiogram--systole or asystole?
AB - A case of stone heart syndrome is reported in a pregnant 27 year old West African
patient, who suffered syncopal symptoms shortly before cardiac arrest. The
electrocardiographic features were those of asystole, but direct examination of
the heart at emergency thoracotomy in the A&E department revealed tetanic
contracture of the organ. At necropsy, the heart was of normal weight but showed
areas of fibrosis surrounding the bundle of His. The discrepancy between the ECG
features and the physiological state of the heart raises the possibility that
other cases of apparent asystole may not be what they seem.
PMID- 9639183
TI - Spontaneous carotid artery dissection presenting as migraine--a diagnosis not to
be missed.
AB - Two cases are reported in which the diagnosis of a serious condition was delayed
as the symptoms had been attributed to migraine. Spontaneous carotid artery
dissection is a serious but treatable cause of headache that may be misdiagnosed
as recent onset migraine. The importance of correctly identifying this condition
is emphasised.
PMID- 9639184
TI - Late clotted haemothorax after blunt chest trauma.
AB - A clotted haemothorax can develop any time after blunt chest trauma. Two cases
are described in which late clotted haemothoraces developed which were treated by
limited thoracotomy and evacuation of clots. Late clotted haemothorax may occur
even in the absence of any abnormal initial clinical findings. Early detection
and treatment is important to avoid the complications of fibrothorax and empyema
with permanent pulmonary dysfunction. After blunt chest trauma patients should be
advised to return to the accident and emergency department for assessment on
development of any new chest symptom. Under these circumstances a chest x ray is
mandatory to exclude a haemothorax.
PMID- 9639185
TI - Out of hospital cardiac arrest and associated injury.
AB - Three patients are described who sustained injuries around the time of a collapse
that led to out of hospital cardiac arrest. In this group of patients the
importance of taking a complete medical history and recording the circumstances
of the syncopal episode cannot be overemphasised. If cardiac output is
successfully restored the possibility of occult traumatic injury must be
considered in high risk patients.
PMID- 9639186
TI - Ectopic pregnancy presenting with obturator nerve pain.
AB - A 27 year old woman had a three day history of pain in the cutaneous distribution
of the left obturator nerve before she developed the classical picture of ectopic
pregnancy with lower abdominal pain and vaginal bleeding. A left tubal pregnancy
was subsequently confirmed by laparoscopy. Referred pain along the obturator
nerve has been reported in other pelvic conditions, but has not previously been
reported as a manifestation of ectopic pregnancy. Ectopic pregnancy may present
with a very wide range of signs and symptoms and should be excluded in females of
child bearing age with unexplained symptoms including pain anywhere from the
shoulder down to the knee.
PMID- 9639187
TI - Clarithromycin induced digoxin toxicity.
AB - A case of digoxin poisoning following the co-administration of digoxin and
clarithromycin in a 28 year old male is described. Since the aetiology of chronic
digoxin poisoning is often unclear, clinicians should be aware of the potential
drug-drug interaction between digoxin and clarithromycin.
PMID- 9639188
TI - Caffeine toxicity in a bodybuilder.
AB - Substance abuse is well documented among bodybuilders and weight lifters keen to
enhance their performance. A case is described of abuse of caffeine to toxic
levels by an amateur bodybuilder and is believed to be the first documented case
of such recreational abuse.
PMID- 9639189
TI - A case of ipsilateral shoulder and elbow dislocation: an easily missed injury.
PMID- 9639190
TI - Spinal tumour: a diagnostic lesson.
PMID- 9639191
TI - Accident and emergency broadsheet: Undergraduate accident and emergency medicine
education broadsheet.
PMID- 9639192
TI - Purchasing new equipment.
PMID- 9639193
TI - Disciplinary procedures.
PMID- 9639194
TI - Is routine computed tomographic (CT) scanning necessary in suspected basal skull
fractures?
PMID- 9639195
TI - Anaesthetic for Colles' fracture.
PMID- 9639196
TI - Sevoflurane.
PMID- 9639197
TI - Traumatic pericardial tamponade.
PMID- 9639198
TI - SHOs' interpretation of x rays.
PMID- 9639199
TI - Curriculum based teaching.
PMID- 9639200
TI - Developments in radiology.
PMID- 9639201
TI - Significance of asymptomatic microhaematuria in men.
PMID- 9639202
TI - Clinical guidelines and standards for the management of uncomplicated genital
chlamydial infection. Central Audit Group in Genitourinary Medicine.
PMID- 9639203
TI - Attitudes to HIV testing in general practice.
AB - Newer therapies for the treatment of HIV infection and the effectiveness of
zidovudine in reducing vertical transmission mean that it is becoming
increasingly important to diagnose HIV infection earlier. General practitioners
(GPs) attending a local study day on sexually transmitted diseases (STDs) were
asked about their likelihood of raising the subject of HIV antibody testing, and
their anxiety when doing so, for different patient groups. A high level of
anxiety was found when raising this topic in certain patient groups, and a
proportion of GPs would never discuss HIV testing, even in very high-risk groups.
No respondents were aware that vertical transmission could be reduced by
antiretroviral drug therapy. These data advocate that the barriers to raising the
issue of HIV testing and the methods of reducing GPs' anxiety associated with it,
need to be addressed.
PMID- 9639204
TI - Systemic immunosuppression by HIV infection influences HPV transcription and thus
local immune responses in condyloma acuminatum.
AB - Human immunodeficiency virus (HIV) infection is considered to influence the
pathogenesis of human papillomavirus (HPV)-associated diseases. It is not clear
whether this occurs directly through molecular interactions between viral genes
and/or indirectly through effects on the immune functions. In the present study
we compared molecular characteristics of penile condylomas from immunocompetent
and HIV-positive individuals. Using polymerase chain reaction (PCR) and reverse
transcriptase (RT)-PCR techniques we determined some characteristics of local
immune responses and transcriptional activity of both viruses. Our findings
revealed that HIV-seropositivity was accompanied by multiple HPV infection and a
CD4-count-dependent appearance of oncogenic HPV-types. HIV infection also changed
the patterns of HPV transcription favouring transcription of early genes such as
E7. Apparently, HIV infection influences local immunity by altering HPV
transcription and by systemic immunodeficiency.
PMID- 9639205
TI - Condom use among Aboriginal people in Ontario, Canada.
AB - A survey of 658 Aboriginal men and women living in 11 reserve communities in
Ontario, Canada, was utilized to collect data on patterns of condom use.
Individuals who had sexual intercourse in the previous 12 months were included in
the analysis (n=400). Descriptive statistics and multiple logistic regression
were used to analyse condom use in the previous 12 months. Eight per cent always,
31% sometimes, and 61% never used condoms. Rates of condom use differed with the
number of sex partners in the last year, age, gender, having a steady sex
partner, and marital status. Multiple logistic regression revealed that people
most likely to use condoms were under the age of 30, male, did not have a long
term steady sex partner, had more than one sex partner, worried about pregnancy,
were knowledgeable about HIV/AIDS, and were not embarrassed to obtain condoms.
Condom users who were knowledgeable about HIV/AIDS and who knew someone with
HIV/AIDS were more likely to always use condoms. The most common reason for not
using a condom was 'I was with my steady sex partner'. These results have
implications for STD prevention efforts and for future research of sexual and STD
preventive behaviour among Aboriginal people.
PMID- 9639206
TI - Hospital service interventions and improving survival of AIDS patients St Mary's
Hospital, London, 1982-1991.
AB - The relationship between changes in hospital service interventions at St Mary's
Hospital, London, reduced case fatality for patients with their first episode of
Pneumocystis carinii pneumonia (PCP) and improved survival from diagnosis of AIDS
was investigated for the period 1982-1991. Multivariate logistic regression
models identified factors independently associated with episode survival; for
those patients who survived their first episode of PCP, survival from time of
diagnosis of AIDS was analysed using multivariate Cox's proportional hazards
models. The case-fatality rate after 1987 was significantly lower for the 159
subjects. Median survival from diagnosis of AIDS increased significantly from 142
days to 554 days (P=0.01). Improved survival of first episode of PCP was
associated with it being the index diagnosis and having a haemoglobin at
diagnosis of PCP greater than 12 g/dl. The presence of a concurrent AIDS-defining
condition in patients who presented with an A-a gradient equal to or greater than
40 mmHg was associated with reduced episode survival, especially before 1987. For
the 126 individuals who survived their first episode of PCP, death rates were
lowest in patients treated with primary or secondary PCP prophylaxis and those
who received zidovudine since their first episode of PCP. Survival in patients
with HIV disease is better in patients who receive appropriate antiretroviral
treatment of HIV infection and timely treatment of opportunistic illnesses. Early
diagnosis of HIV-1 infection with early diagnosis and treatment of first episode
of PCP was associated with improved episode survival. Subsequent medical follow
up combined with PCP prophylaxis and zidovudine were significantly associated
with long-term survival.
PMID- 9639207
TI - Sexually transmitted disease rates before and after HIV testing.
AB - The aim of the study was to evaluate the effect of having an HIV-positive or
negative test result on sexual risk behaviour before and after the test.
Longitudinal retrospective case-note survey identifying new episodes of sexually
transmitted disease (STD) infections in 114 subjects testing HIV positive and 114
matched negatives were examined at the Genitourinary Medicine Department, St
Mary's Hospital, Paddington, London. Across the whole sample in the year after
HIV testing the number of cases of new STD infections was 40% of the number of
cases in the year prior to HIV testing. There was no association between
serostatus and incidence of STD infections before and after HIV testing. Of those
testing negative, 5.3% were identified as having a new infection in the year
after the HIV test, while amongst those testing positive there was a rate of new
STDs of 2.6%. In conclusion, there was no evidence that having a negative test
result increased the risk of acquisition of new STDs. Rates of new STD infections
amongst seropositives in the year after HIV testing were low.
PMID- 9639208
TI - HIV, STDs, anal sex and AIDS prevention policy in a northeastern Brazilian city.
AB - Data on HIV/AIDS, other STDs, and related sexual practices and AIDS prevention
measures in Sao Luis, capital of Maranhao state, were collected in May-July 1995
using participant-observation fieldwork, including a number of face-to-face
interviews in addition to archival research, and were updated by correspondence
in 1996-1997 and a brief visit in February 1998. In contrast to the continuing
severe AIDS epidemic in southern Brazil, public health statistics and public HIV
testing recently instituted in Sao Luis suggest that HIV infection has remained
largely concentrated among men who have sex with men, as well as a few, though
growing number of cases of women evidently infected by such men. However, other
STDs are endemic to the region, and could provide an increasing portal of entry
for HIV infection. AIDS prevention education programmes have commenced in public
schools and elsewhere in Sao Luis, but greater emphasis needs to also be placed
on the prevention and treatment of other STDs. As in other regions of Brazil and
Latin America, the reportedly common practice of anal sex among heterosexuals
also represents a significant yet typically underemphasized risk factor for HIV.
PMID- 9639209
TI - Outcome of inflammatory smears managed in a genitourinary medicine clinic.
PMID- 9639210
TI - An audit of cervical cytological screening amongst HIV-positive women.
PMID- 9639211
TI - Cervical smear: is screening of teenagers justified?
PMID- 9639212
TI - Charter mark for genitourinary medicine.
PMID- 9639213
TI - Genitourinary medicine services in Manchester Royal Infirmary.
PMID- 9639214
TI - Occult anal sphincter trauma following randomized forceps and vacuum delivery.
AB - OBJECTIVE: To determine the prevalence of occult anal sphincter trauma 5 years
after randomization to forceps and vacuum delivery. METHOD: Anal endosonography
and manometry was performed in 44 of 313 women who had originally participated in
one center of the Keele University Multicenter Assisted Delivery Trial at the
North Staffordshire Maternity Hospital between September 1989 and May 1990.
RESULTS: 50% admitted to defecatory symptoms and anal sphincter defects were
identified in 61%. On the basis of intention to treat, 82% of forceps (n = 17)
and 48% of vacuum deliveries (n = 27) had occult sphincter defects (P = 0.03). In
four women, both instruments were used. However, the preponderance of defects in
the forceps group persisted even when analysis was performed according to the
final mode of delivery as well as in the group where only one instrument was used
(n = 40). There was a significant fall in maximum squeeze anal pressure in the
forceps group compared to the vacuum group (56 vs. 36 mmHg; P = 0.0007). Although
twice as many in the forceps group suffered anal incontinence (32% vs. 16%)
significance was not reached. CONCLUSIONS: Vacuum delivery appears to be
associated with less occult anal sphincter trauma than forceps delivery. A large
prospective randomized study is required to address the impact of specific
situations, such as failed instrumentation with use of a second instrument and
rotational delivery.
PMID- 9639215
TI - Second trimester calcium-phosphorus-magnesium homeostasis in women with
threatened preterm delivery.
AB - OBJECTIVE: The effect of threatened preterm delivery on calcium, phosphorus,
magnesium homeostasis in the second trimester of pregnancy was investigated.
METHODS: Serum concentrations of total and ionized calcium, inorganic phosphorus,
magnesium, total protein, albumin, total estrogens and human placental lactogen
were determined in women with threatened preterm delivery at 23-28 weeks of
gestation (the studied group) and in women with uncomplicated pregnancy of the
same duration (the control group). Additionally activities of total alkaline
phosphatase and heat-stable alkaline phosphatase fraction were measured. RESULTS:
Patients of the studied group compared to the control group showed decreased
concentration of total calcium (2.15 +/- 0.073 vs. 2.25 +/- 0.11 mmol/l, P <
0.001), inorganic phosphorus (1.21 +/- 0.26 vs. 1.34 +/- 0.22 mmol/l, P < 0.01)
and magnesium (0.63 +/- 0.053 vs. 0.71 +/- 0.12 mmol/l, P < 0.001), total protein
(64.0 +/- 5.4 vs. 68.6 + 1.0 g/l, P < 0.001), albumin (546.3 +/- 55.1 vs. 579.6
+/- 49.3 micromol/l, P < 0.003) and placental lactogen (3664 +/- 1806 vs. 4651 +/
1858 ng/ml, P < 0.02); they also demonstrated decreased activity of total
alkaline phosphatase (42.17 +/- 16.99 vs. 50.66 +/- 6.56 IU/l, P < 0.001) and its
heat stable fraction (22.65 +/- 7.89 vs. 31.89 +/- 9.09 IU/l, P < 0.001).
Patients of the studied group showed normal values of ionized calcium and total
estrogens. CONCLUSIONS: Premature uterine contractility in women in the second
trimester is accompanied by lowered serum concentrations of total calcium,
inorganic phosphorus, magnesium, total protein and albumin. There is also
decreased activity of total alkaline phosphatase, its heat-stable fraction and
placental lactogen which may have diagnostic value. Premature uterine
contractility in women in the second trimester may be related to the disturbances
of calcium-phosphorus-magnesium homeostasis and calcium supplementation should be
considered.
PMID- 9639216
TI - Intensification of fetal and maternal surveillance in pregnant women with
hypertensive disorders.
AB - OBJECTIVE: To examine the need to intensify fetal and maternal surveillance in
pregnant women with mild pregnancy hypertension. METHODS: The multi-center cohort
study in 2413 healthy nulliparae analyzed differences in hypertension-related
adverse events (small-for-gestational age, perinatal mortality, eclampsia,
abruptio placentae and HELLP syndrome) according to maximum diastolic blood
pressure and proteinuria. RESULTS: Compared to the reference group (diastolic
blood pressure 70-85 mmHg) (n = 1882) the relative risks of adverse fetal and
maternal outcome in 34 proteinuric hypertensive women were 8.9 (95% CI 3.3-24.1)
and 41.5 (95% CI 9.7-178.4), respectively. In 203 non-proteinuric women with a
maximum diastolic blood pressure of > or = 95 mmHg only the relative risk of
adverse maternal outcome was increased (11.6, 95% CI 3.1-42.8), but it was not
increased in 230 non-proteinuric women with a maximum diastolic of 90 mmHg.
CONCLUSIONS: Intensified surveillance in women with mild pregnancy hypertension
is not indicated and should be reserved for groups with increased fetal and
maternal risk.
PMID- 9639217
TI - Amnioinfusion in labor induction of term pregnancies with premature rupture of
the membranes and low amniotic fluid.
AB - OBJECTIVE: To analyze the utility of prophylactic amnioinfusion in term
pregnancies with PROM and a low amniotic fluid index during labor induction.
METHOD: Forty-two women with amnioinfusion and 42 in a control group with
amniotic fluid index (AFI) below 10 cm when admitted to labor induction were
studied. All patients had electronic fetal heart rate and intrauterine pressure
continuous monitoring. Amnioinfusion of normal saline (37 degrees C) was realized
in the study group, using a continuous perfusion pump at 600 ml/h for 1 h, after
which the AFI was again recorded; if this was < 15, the perfusion was continued
at 180 ml/h until full cervical dilatation was achieved or until uterine baseline
activity reached 20 mm Hg. The control group received identical obstetric care
except in respect of amnioinfusion. RESULT: Both groups were similar in age,
primiparity, gestational age, initial AFI, interval from rupture of membranes
until delivery and length of labor. The amnioinfusion of 600 ml in 1 h
significantly increased the AFI (an increase of 7.2 +/- 3.9 vs. a decrease of 1.1
+/- 1.6, P < 0.01). In the amnioinfusion group, there was a significantly lower
rate of cesarean deliveries (0 vs. 6, P < 0.05) and a better mean umbilical
arterial pH at delivery (7.24 +/- 0.07 vs. 7.21 +/- 0.08, P < 0.05). No
differences were observed in maternal or neonatal hospitalization days or
infectious morbidity. CONCLUSION: It is concluded that prophylactic amnioinfusion
improves neonatal metabolic state when used in labor induction of term
pregnancies with PROM and a low amniotic fluid index.
PMID- 9639218
TI - Effects of postpartum corticosteroids in patients with HELLP syndrome.
AB - OBJECTIVE: To evaluate the effect of corticosteroid treatment on the postpartum
recovery of parturients with HELLP syndrome. METHOD: Thirty cases with HELLP
syndrome were randomly assigned to a study or a control group, each including 15
patients. A total dose of 30 mg intravenous dexamethasone was given to the study
group during the 36 h following the childbirth, while the control group did not
receive any steroid medication. Arterial blood pressure, urine output, hematocrit
ratio, platelet count, serum alanine and aspartate aminotransferases and uric
acid levels were monitored during the first 48 h postpartum. The data were
analyzed by unpaired t-test, chi2 or Fisher's exact tests. RESULT: Before the
treatment, no significant difference was observed between the two groups. The
study group showed statistically significant improvement in mean arterial blood
pressure, mean serum aspartate aminotransferase level, mean urine volume per hour
and mean platelet count (P < 0.05). Length of hospitalization was also shorter in
the study group (P < 0.01). CONCLUSION: Early postpartum high-dose corticosteroid
treatment accelerates the recovery and shortens the hospitalization of the
parturients with HELLP syndrome.
PMID- 9639219
TI - Fluorescence microsatellite analysis to study the parental origin of the
supernumerary chromosome in Down's syndrome.
AB - OBJECTIVE: Down's syndrome (DS) is an important cause of mental retardation. This
study investigated the parental origin of the extra chromosome 21 in DS patients.
METHODS: Fourteen families each with a DS patient were recruited for analysis of
nine microsatellite markers on chromosome 21. We collected DNA from both parents
and the patient and used polymerase chain reaction to amplify nine segments on
chromosome 21: D21S1435, D21S1436, D21S1437, D21S1446, D21S156, D21S258, D21S263,
D21S265 and D21S270. One of each pair of DNA primers was labeled with a
fluorescence dye. The amplified products were subjected to electrophoresis in a
semi-automated DNA sequencer and then analyzed with Genescan software to
determine the origin of the extra chromosome 21. RESULTS: The extra chromosome 21
originated from the mother in 13 (93%) patients and from the father in one (7%)
patient. CONCLUSIONS: Our findings were compatible with those from Caucasian
patients. A great majority of Down's syndrome cases resulted from meiotic errors
in the eggs.
PMID- 9639220
TI - Maternal and perinatal outcomes of multiple pregnancy following IVF-ET.
AB - OBJECTIVE: To analyze the course of pregnancy and perinatal outcome in 31 twins,
22 sets of triplets and five quadruplet clinical pregnancies following
conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection
(ICSI) procedures and in relation to 58 singleton pregnancy following the same
procedure. METHODS: Retrospective analysis of maternal and neonatal medical
records of 58 singleton, 31 twin, 22 triplet and five quadruplet pregnancies
diagnosed at 7-8 weeks gestation following 561 embryo transfer procedures in 628
oocyte collections at the IVF Center in the Maternity Hospital, Kuwait from July
1994 to December 1996. RESULTS: The clinical pregnancy rate in 628 cycles
proceeding to oocyte collection was 32.6%, there being 58 singletons (50.6%), 31
twins (33.5%), 22 triplets (10.8%) and five quadruplets (2.5%). Early complicated
outcomes included 47 miscarriages (23.7%), four ectopic pregnancies (1.9%) and
one hydatidiform mole. The spontaneous fetal reduction rate was 20.6% in twin,
45.5% in triplet and 40% in quadruplet pregnancies. There was a significantly
higher maternal and neonatal complication rate in the triplet group compared to
singletons and twins, including threatened miscarriage, pre-eclampsia, antepartum
hemorrhage, longer hospital stay and preterm labor. The chance of operative
delivery was higher in high-order multiple pregnancy (HOMP). The major neonatal
complications were related to prematurity. Neonatal morbidity and mortality were
significantly higher in the triplet group. The need for admission to the Special
Care Baby Unit (SCBU) and the Neonatal Intensive Care Unit (NICU) was
significantly higher in HOMP. However, there were no statistically significant
differences in the perinatal mortality in relation to the degree of HOMP.
CONCLUSION: Maternal complications, perinatal and neonatal morbidity after 2
years activities in the IVF Center have been reviewed leading to changes in
policies of management, notably a reduction in the number of embryos transferred.
PMID- 9639221
TI - Simplified abdominal wall-lifting device for gasless laparoscopy.
AB - OBJECTIVE: To develop a simplified abdominal wall-lifting device for gasless
laparoscopy. METHODS: The device is composed of an electric-power actuator,
sliding arm and abdominal wall-retractor. All parts of the device are reusable.
The device provides planar displacement of the anterior abdominal wall to enable
space for laparoscopy. The valveless ports and conventional instruments, as well
as laparoscopic instruments, were used without a gas leak problem. RESULTS: After
preliminary success in the laboratory testing, a petition was made to the
hospital's Ethic Committee. Since then we have performed 40 gasless laparoscopic
procedures including 13 salpingo-oophorectomies, 10 diagnostic laparoscopies,
five tubal ligations, five ovarian cystectomies, four salpingectomies, two
removals of pelvic IUDs and one laparoscopic hysterectomy. There were no surgical
complications, including no abdominal wall trauma. The operative field was almost
the same as that of the pneumoperitoneum technique, with the exception of
morbidly obese patients. CONCLUSIONS: This preliminary experience demonstrates
the efficiency of the simplified abdominal wall-lifting device and the potential
advantages of gasless laparoscopy. Continued modifications and applications are
necessary to delineate the full range of benefits of this device and technique,
especially in developing countries.
PMID- 9639222
TI - Oral glucose challenge effects on growth and sex steroid hormones in normal women
and women with hypothalamic amenorrhea.
AB - OBJECTIVE: To investigate the effect of growth hormone (GH) on the serum levels
of ovarian and adrenal sex steroid hormones in women with hypothalamic amenorrhea
(HA). METHODS: A standard 75-g oral glucose tolerance test (OGTT) was performed
in 12 normal women and 16 women with stress-related or weight-loss-related
amenorrhea. RESULTS: Significant progressive declines in GH, testosterone (T),
estradiol (E2) and dehydroepiandrosterone sulfate (DHEAS) were observed during
the OGTT in the normal and HA groups. Significant positive correlations were
observed between GH and T, E2 and DHEAS. The area under the curve (AUC) for the
GH response was significantly greater in the HA group than in the normal group.
The ratio of the AUC of insulin-like growth factor to that of GH was
significantly lower in the HA group. CONCLUSIONS: Growth hormone may modify
ovarian and adrenal sex steroidogenic responses to tropic hormones. A significant
degree of GH resistance exists in HA patients. This GH resistance may be related
to an ovulatory disturbance.
PMID- 9639223
TI - A maternity waiting home experience in Zimbabwe.
PMID- 9639224
TI - Jaundice induced by hyperemesis gravidarum.
PMID- 9639225
TI - Cessation of drug use and infant birth weight.
PMID- 9639226
TI - Elective Shirodkar procedure: prognostic factors and postoperative pregnancy
outcome.
PMID- 9639227
TI - Acrania, MTHFR 677C-->T mutation and role of folate intake.
PMID- 9639228
TI - Leiomyomatosis peritonealis disseminata.
PMID- 9639229
TI - ACOG educational bulletin. Antiphospholipid syndrome. Number 244, February 1998.
American College of Obstetricians and Gynecologists.
PMID- 9639230
TI - ACOG committee opinion. Role of loop electrosurgical excision procedure in the
evaluation of abnormal Pap test results. Number 195, November 1997. Committee on
Gynecologic Practice. American College of Obstetricians and Gynecologists.
PMID- 9639231
TI - ACOG committee opinion. Vitamin A supplementation during pregnancy. Number 196,
January 1998 (replaces No. 157, September 1995). Committee on Obstetric Practice.
American College of Obstetricians and Gynecologists.
PMID- 9639232
TI - ACOG criteria set. Quality evaluation and improvement in practice. Tocolysis.
Number 31, February 1998. Committee on Quality Assessment. American College of
Obstetricians and Gynecologists.
PMID- 9639233
TI - Behavioral tolerance to and withdrawal from multiple fluoxetine administration.
AB - The objective of this study was to characterize the lasting effects of fluoxetine
on the locomotor behavior of rats using a computerized activity-monitoring
system. Challenge dosages (8, 16, and 24 mg/kg i.p.) of fluoxetine 2 h into the
dark phase resulted in dose-dependent suppression of locomotor activity for 4 h
following injection. Escalating (10-30 mg/kg i.p.) semidaily fluoxetine
administration for the next five days resulted in decreasing locomotor activity
during the multiple-administration period relative to saline control. Circadian
activity patterns at the conclusion of the regimen were unchanged in shape, but
featured uniform decreases in locomotor activity at every hour which were more
significant during the phase. Upon discontinuation, fluoxetine-treated rats
showed a significant increase in activity during the first 4 h following the
first "missed" dose which was not seen in subsequent washout. Ninety-six h after
the final maintenance dose, the initial three dosages were readministered, and
the locomotor activity suppression in response to the rechallenge dose of
fluoxetine was significantly lessened compared to initial challenge. These
findings suggest that tolerance and withdrawal were obtained.
PMID- 9639234
TI - Crossed cerebro-cellular diaschisis in a patients with melas with aphasia but
without hemiparesis.
AB - We describe a 25 year old woman diagnosed with MELAS during an acute stroke-like
episode. Global aphasia, migraine-like headaches and hemi-anopsia were her main
clinical features. MR imaging revealed extensive cortical and subcortical left
hemispheric signal abnormalities. [Tc-99m]ECD SPECT scanning revealed crossed
cerebrocerebellar diaschisis. Aphasia in the absence of gross hemiparesis can be
related to cross-cerebellar diaschisis in MELAS.
PMID- 9639235
TI - Acoustic startle electromyographic (EMG) activity indexed from an
electroculographic (EOG) electrode placement: a methodological note.
AB - Acoustic startle EMG responses were indexed from a traditional EOG electrode
placement in 11 young adults while they viewed slides which varied in affective
valence. We found, replicating earlier work that subjects' startle responses
became more augmented as the content of the slides became more negative. The
advantages of using an EOG electrode placement for measuring acoustic startle
responses are discussed.
PMID- 9639236
TI - Is backward stepping over obstacles achieved through a simple temporal reversal
of forward stepping?
AB - The main purpose of the study was to examine whether backward stepping over
obstacles was a simple temporal reversal of kinematic and muscle activation
patterns found in forward obstacle avoidance. Obstacle avoidance was used as a
probe to represent one aspect of walking over variable terrain. Kinematics,
trajectories and muscle activation profiles for forward versus backward stepping
over obstacles revealed that the simple reversal of locomotor patterns observed
for level walking cannot be applied to obstacle avoidance. However, key kinematic
data and limb trajectories for backward leading limb stepping were found to be
similar to existing forward trailing limb data. Therefore, it appears that
stepping over obstacles requires a complex upper level reorganization of the
basic locomotor pattern based on biomechanical and sensory feedback.
PMID- 9639237
TI - Utility of the seven subtest WAIS-R short form in a female sample with brain
damage.
AB - We examined the accuracy of the WAIS-R seven subtest short form (Ward, 1990) for
predicting IQs of 130 females with brain damage or dysfunction. Means for age,
education, and FSIQ were 44.37 years (SD = 18.46), 12.74 years (SD = 2.42), and
87.64 (SD = 13.62). Results indicated that 93%, 84%, and 93% of short form
estimated VIQs, PIQs, and FSIQs were within +/-5 points of their actual WAIS-R
scores. In terms of Wechsler's (1981) seven category intelligence classification,
levels of agreement were 83%, 72%, and 82% for the Verbal, Performance, and Full
scales, respectively. These findings support the use of the seven subtest short
form with brain-damaged women when time is at a premium and only a general
estimate of intellectual functioning is required.
PMID- 9639238
TI - Smell and taste of chewing gum affect frequency domain EEG source localizations.
AB - We investigated brain electric field signatures of subjective feelings after
chewing regular gum or gum base without flavor. 19-channel eyes-closed EEG from
20 healthy males before and after 5 minutes of chewing the two gum types in
random sequence was source modeled in the frequency domain using the FFT-Dipole
Approximation. 3-dimensional brain locations and strengths (Global Field Power,
GFP) of the equivalent sources of five frequency bands were computed as changes
from pre-chewing baseline. Gum types differed (ANOVA) in pre-post changes of
source locations for the alpha-2 band (to anterior and right after regular gum,
opposite after gum base) and beta-2 band (to anterior and inferior after regular
gum, opposite after gum base), and of GFP for delta-theta, alpha-2 and beta-1
(regular gum: increase. gum base: decrease). Subjective feeling changed to more
positive values after regular gum than gum base (ANOVA).--Thus, chewing gum with
and without taste-smell activates different brain neuronal populations.
PMID- 9639239
TI - ATP-sensitive potassium channels mediate norepinephrine- and morphine-induced
antinociception at the spinal cord level.
AB - The effects of intrathecally (i.t.) administered glibenclamide, a blocker of
adenosine triphosphate-sensitive potassium ( KATP) channels, on antinociception
produced by i.t. norepinephrine, morphine, or 5'-N-ethylcarboxamide adenosine, an
adenosine agonist, were investigated using tail-flick assay. The results showed
that: 1) i.t. norepinephrine (1 nmol), morphine (0.5 nmol) and 5'-N
ethylcarboxamide adenosine (0.5 nmol) elicited prolongation of tail-flick
latency, 2) i.t. glibenclamide given in 2 different doses (5 and 10 nmol)
exhibited no effects on tail-flick latency, 3) the antinociception produced by
norepinephrine (1 nmol) and morphine (0.5 nmol) was blocked by glibenclamide in a
dose-dependent manner, 4) glibenclamide failed to modulate the effects of 5'-N
ethylcarboxamide adenosine on tail-flick latency. These observations suggest that
KATP channels may play an important role in norepinephrine- and/or morphine
induced antinociception at the spinal level.
PMID- 9639240
TI - Using event-related potentials to examine pharmacological effects on intervening
cognitive functions in rats.
AB - Assessing toxicological and pharmacological effects on cognition using sensory
evoked potentials and purposive behaviors as endpoints may limit testing to
afferent activity and to populations able to follow directions. The present study
uses a non-invasive method that does not require training or response to
instruction to measure the brain's longer latency intervening cognitive response
to stimulation. The averaged electrophysiological responses of 8 rat brains,
Event-Related Potentials (ERPs), were recorded in 3 spatial dimensions and time
while they experienced two time varying modes of auditory stimulation and
anesthesia. Results show that both modes of stimulation elicited ERPs with
similar magnitudes and latencies but with different electrophysiological patterns
at each level of anesthesia. These results suggest anesthesia may not effect the
brain's ability to detect and represent an input, but rather its ability to
inhibit that input's decay over time so it can consolidate into a form able to
benefit future processing. Anesthesia effected these events during the two modes
of stimulation differently over time, suggesting this method of stimulation and
recording may provide dependent variables sensitive to the brain's response at
different dose levels.
PMID- 9639241
TI - Treatment with AC pulsed electromagnetic fields normalizes the latency of the
visual evoked response in a multiple sclerosis patient with optic atrophy.
AB - Visual evoked response (VER) studies have been utilized as supportive information
for the diagnosis of multiple sclerosis (MS) and may be useful in objectively
monitoring the effects of various therapeutic modalities. Delayed latency of the
VER, which reflects slowed impulse transmission in the optic pathways, is the
most characteristic abnormality associated with the disease. Brief transcranial
applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux
density are efficacious in the symptomatic treatment of MS and may also
reestablish impulse transmission in the optic pathways. A 36 year old man
developed an attack of right sided optic neuritis at the age of 30. On
presentation he had blurring of vision with reduced acuity on the right and
fundoscopic examination revealed pallor of the optic disc. A checkerboard pattern
reversal VER showed a delayed latency to right eye stimulation (P100 = 132 ms;
normal range: 95-115 ms). After he received two successive applications of AC
pulsed EMFs of 7.5 picotesla flux density each of 20 minutes duration
administered transcranially, there was a dramatic improvement in vision and the
VER latency reverted to normal (P100= 107 ms). The rapid improvement in vision
coupled with the normalization of the VER latency despite the presence of optic
atrophy, which reflects chronic demyelination of the optic nerve, cannot be
explained on the basis of partial or full reformation of myelin. It is proposed
that in MS synaptic neurotransmitter deficiency is associated with the visual
impairment and delayed VER latency following optic neuritis and that the recovery
of the VER latency by treatment with pulsed EMFs is related to enhancement of
synaptic neurotransmitter functions in the retina and central optic pathways.
Recovery of the VER latency in MS patients may have important implications with
respect to the treatment of visual impairment and prevention of visual loss.
Specifically, repeated pulsed applications of EMFs may maintain impulse
transmission in the optic nerve and thus potentially sustain its viability.
PMID- 9639242
TI - A neuromagnetic view of hippocampal memory functions.
AB - Bursts of highly synchronized discharges of 4-7Hz sinusoidal wave activity can be
recorded from the hippocampus during rapid eye movement (REM) sleep. These
rhythmic discharges, the hippocampal theta activity, are generated in the dentate
granule cells and the pyramidal cell layers of the CA1 field of the hippocampus.
The physiological function of the hippocampal theta activity is elusive. The
occurrence of this rhythm throughout the REM sleep stage suggests that it is
related to some fundamental neurophysiological phenomena associated with REM
sleep, particularly consolidation of memory processes. Synchronous oscillations
among a population of neurons are expected to yield stronger, more coherent
associated magnetic fields which, through their influence back on the electrical
fields via induction, would exert an independent effect on the electrical
activity of hippocampal neurons and additionally, could foster and reinforce
these oscillations through self-induction. The snail-shaped structure of the
hippocampal formation, which resembles a solenoid embedded in the temporal lobe,
would be expected to amplify these magnetic fields. Additionally, the discovery
of large ferromagnetic particles in the human hippocampus suggests that it may
function as a large iron-core electromagnet. It is proposed that memory traces
may be encoded or decoded magnetically and analogous to a videotape, each
encoding unit (i.e., synapse, set of synapses or glial cell) could be magnetized
in one direction, or the other through the flow of a strong, AC magnetic field
along the hippocampal formation. The encoding of memory traces in the hippocampal
formation may ultimately reflect an electromagnetic phenomenon.
PMID- 9639243
TI - Age-dependent effect of ketanserin on the sleep-waking phases in rats.
AB - The age-dependent effect of the specific 5-HT2 receptor antagonist ketanserin at
two doses (1 mg/kg and 6 mg/kg) on six sleep-waking phases was
electroencephalographically (EEG) examined in young, middle-aged, and old male
Wistar rats. Because 5-HT2 receptor binding sites decrease with aging, the
question of whether ketanserin can produce any effect on sleep-wake in advanced
age was addressed. Ketanserin enhanced deep slow wave sleep in the three age
groups. However, in the old rats this effect was much less pronounced and did not
depend on the dose. Only in the young and middle-aged animals, ketanserin reduced
wakefulness in a dose-dependent manner. The suppression of paradoxical sleep with
ketanserin did not depend on the age. The results suggest that the model of aging
may be useful to study the functional role of 5-HT2 receptors in sleep-waking
regulation.
PMID- 9639244
TI - Age-related effect of ritanserin on the sleep-waking phases in rats.
AB - The age-related effect of the specific 5-hydroxytryptamine-2A/2C (5-HT(2A/2C))
antagonist ritanserin at two doses 0.63 mg/kg and 2.5 mg/kg) on six sleep-waking
phases in young, middle-aged, and old male Wistar rats was
electroencephalographically (EEG) examined. Only in the young and middle-aged
rats, ritanserin enhanced slow wave sleep and reduced wakefulness in a dose
dependent manner. Ritanserin suppressed paradoxical sleep, such that this effect
did not depend on the age. Although the effect of ritanserin on slow wave sleep
was significantly smaller in the old compared to the young and the middle-aged
rats, ritanserin produced an apparent sleep-improving effect in the old age
group.
PMID- 9639245
TI - Dichotic memory: paradoxical effect of removing a left frontal gyrus: a case
study.
AB - A 27-year-old right-handed woman was operated with resection of an epileptogenic
lesion, a nonmalignant tumor, in the left frontal lobe. The surrounding cortical
and subcortical tissue in the tumor-containing gyrus was also resected. Care was
taken during the operation not to interfere with motor or language related
cortical areas. Pre- and postoperatively, she was tested with a dichotic memory
test. In the preoperative test, she showed a marked Left Ear Advantage. In the
corresponding tests on the second and fourth postoperative days and at follow-up,
her performance had changed to a Right Ear Advantage. A possible explanation of
this result is that neighboring cortical areas involved in hemispheric
specialization for lateralized, verbal cognitive functions are suppressed by a
focal epiletogeneic activity caused by the tumor. The subsequent removal of this
influence allowed these cortical areas to function normally.
PMID- 9639246
TI - The in vitro effect of substance P on the GnRH-induced LH release depends on the
steroidal environment and is reverted by a NK1 receptor antagonist (RP 67580) in
the cycling female rat.
AB - A previously study reported that administration of substance P on the morning of
the proestrous day induces an inhibition of afternoon gonadotropin preovulatory
surges in the female rat. It has also been shown, with a non-peptide specific
antagonist of the neurokinin 1 (NK1) receptor (RP 67580), that this effect is
mediated by NK1 receptors. The present study used perifused anterior pituitaries
from proestrous morning female rats and showed that the SP modulation of the GnRH
induced LH release is markedly dependent on the steroidal environment. In the
absence of steroids or in the presence of 17beta estradiol, or a combination of
17beta estradiol and progesterone, SP inhibited the GnRH-induced LH release. In
contrast, SP stimulated the GnRH-induced LH secretion in the presence of
progesterone alone. However, the inhibitory or stimulatory effect of SP was
antagonized by the specific NK1 receptor antagonist RP 67580.
PMID- 9639247
TI - Cholecystokinin peptides and receptor binding in rat brain after DSP-4 treatment.
AB - The neurotoxin DSP-4 has, in this laboratory, previously been shown to upregulate
cholecystokinin (CCK) binding in the frontal cortex and the hippocampus in rats.
The present study investigated the effect of DSP-4 on CCK peptide levels and CCK
receptor binding in some rat brain areas. Sprague-Dawley rats were given single
injections of DSP-4 (10 and 50 mg/kg) and examined after 1 week. Wistar rats were
given an injection of DSP-4 (50 mg/kg) and evaluated 1 week and 4 months after
treatment. No significant changes in CCK levels or in CCK binding were found. It
has been found that stress produced by handling of the rats immediately before
decapitation can result in an increase in cortical CCK receptor binding. This
finding led to the speculation that the upregulation of CCK binding after DSP-4
treatment which was reported earlier, reflects a stress-potentiating effect of
DSP-4.
PMID- 9639248
TI - A comparison of actions of neuropeptide Y (NPY) agonists and antagonists at NPY
Y1 and Y2 receptors in anaesthetized rats.
AB - The pancreatic polypeptide family includes three members, neuropeptide Y (NPY),
peptide YY (PYY) and pancreatic polypeptide (PP), with sequence homology between
members and species varying from approximately 50 to 80%. Some of these peptides
were compared in the mammalian cardiovascular system for activity mediated by
actions on pre- (Y2) and post-junctional (Y1) NPY receptors. NPY and PYY, with
sequence homology of 67% have similar actions on Y1 and Y2 receptors. Rat
pancreatic polypeptide (rPP) with sequence homology of approximately 50% is
inactive at both. This study reports that the chimeric peptide, hPP1-11/NPY12-36
and the truncated peptide NPY2-36 show similar activity to NPY mediated through
both receptor types in vivo, while salmon PYY (sPYY), with 81% homology to NPY,
has improved potency at both receptor subtypes. NPY3-36 has equal activity with
NPY on actions mediated through Y2 receptors, but significantly reduced activity
mediated through Y1 receptors. Two NPY antagonists were also examined: PYX2 was
inactive in vivo and 1229U91 showed potent, long-lasting activity on Y1 receptor
mediated effects.
PMID- 9639249
TI - Measurement of cytokines in the cavernous sinus plasma from patients with
Cushing's disease.
AB - In order to know more about the in vivo secretion of various cytokines from the
human pituitary, this study measured the concentrations of interleukin (IL)
1alpha, IL-1beta, IL-2, IL-6, tumor necrosis factor-alpha and IL-1 receptor
antagonist (ra) in both the peripheral blood and the cavernous sinus (CS) plasma
from six patients with Cushing's disease before and after an intravenous bolus
injection of human corticotropin-releasing hormone (CRH, 100 microg). As a
routine procedure for the diagnosis of Cushing's disease, adrenocorticotropin
(ACTH) levels were also determined in the same samples. In four of the six
patients, unstimulated levels of IL-1ra in the CS ipsilateral to the ACTH
secreting adenoma were higher than those in the peripheral blood, with a ratio of
> or = 1.5:1, even though CRH was without effect on the cytokine's concentration
in the CS. In contrast, no consistent data were obtained for any of the remaining
five cytokines. These results demonstrate for the first time that the in vivo
release of IL-1ra is detectable in at least some corticotroph adenomas, and also
suggest a possible role of the cytokine in physiological and pathophysiological
processes occurring in the human pituitary.
PMID- 9639250
TI - Effect of melatonin on arginine vasopressin secretion stimulated by physical
exercise or angiotensin II in normal men.
AB - The present study was undertaken in order to establish the possible involvement
of melatonin in the mechanisms underlying the arginine-vasopressin (AVP)
responses to physical exercise and angiotensin II (ANG II). On two mornings at
least 1 week apart, normal male subjects were tested with exercise on a bicycle
ergometer (the workload was gradually increased at 3-min intervals until
exhaustion and lasted about 15 min in all subjects) or ANG II (60-min infusion of
ANG II (Asp 1, IIe 5 angiotensin II) dissolved in 5% glucose in successively
increasing doses of 4, 8, 16 ng/kg/min; each dose for 20 min). Tests were carried
out with the administration of either 6 mg melatonin or placebo. Melatonin
treatment neither modified the basal concentrations of AVP nor changed the AVP
response to ANG II. In contrast, plasma AVP levels rose 3.6 times during exercise
in the absence of melatonin, but only 2.3 times in the presence of melatonin.
These data indicate an involvement of melatonin in the mechanism underlying the
AVP response to physical exercise, but not ANG II, in normal men.
PMID- 9639251
TI - The C-terminal tetrapeptide of beta-endorphin (MPF) enhances lymphocyte
proliferative responses.
AB - Human MPF (Lys-Lys-Gly-Glu) stimulates the proliferative response of human
lymphocytes to the T-cell mitogen concanavalin A by 121-751% in the concentration
range 10(-11)-10(-4) M; the peak effect is at 10(-8) M, lower or higher
concentrations eliciting reduced responses, i.e. the dose-response curve is bell
shaped. Species specificity is high. Human MPF similarly stimulates rat
lymphocytes, but the peak effect is seen at a 100-fold higher dose (10(-6) M).
Rat MPF (Lys-Lys-Gly-Gln) has a peak effect at 10(-6) M with human lymphocytes,
but the peak effect with rat lymphocytes is at a 1000-fold lower dose (10(-9) M).
Truncated forms of the MPFs (Gly-Glu, Gly-Gln, Gly, Glu, Gln) and opioid peptides
(beta-endorphin, [Leu] and [Met]enkephalin) show insignificant or only weak
stimulatory or inhibitory effects. These results suggest that MPF acts via
specific non-opioid receptors located on lymphocytes and that endogenously
released MPF may have an important role in the functioning of the immune system.
PMID- 9639252
TI - Penetration of dynorphin 1-13 across the blood-brain barrier.
AB - Previous studies have demonstrated neuroprotective effects of the opioid peptide
dynorphin (dyn) 1-13 in focal cerebral ischemia. The passage of dyn 1-13 across
the blood-brain barrier (BBB) was studied by a modification of the Oldendorf
technique in the normal rat and cat, as well as in a feline model of
experimentally induced focal cerebral ischemia. In the rat, dyn 1-13 penetration
of the BBB could not be detected by this technique, even in the presence of
peptidase inhibitors. In contrast, dyn 1-13 did cross the BBB into the normal cat
hippocampus, cortex and cerebellum. The passage of dyn 1-13 across the BBB was
greater in cats with experimentally induced focal cerebral ischemia. Some of the
tritium-labeled material which crossed the BBB was confirmed by high performance
liquid chromatography to be dyn 1-13. These studies support the hypothesis that
the therapeutic effects observed after the peripheral administration of dyn 1-13
to cats with focal cerebral ischemia can be produced by a central mechanism of
action.
PMID- 9639253
TI - Diabetic rats are unresponsive to the penile erection-inducing effect of
intracerebroventriculary injected adrenocorticotropin.
AB - The penile erection-inducing effect of intracerebroventricularly (i.c.v.)
injected adrenocorticotropin-(1-24) [ACTH-(1-24)] (4 or 10 microg/animal) was
almost completely absent in diabetic rats, either 8 days or 2 months after
streptozotocin administration. The other behavioral symptoms (stretching,
yawning, excessive grooming) were unevenly affected: stretching was significantly
reduced either in early or in long-standing diabetes; yawning was practically
absent in early diabetes and significantly reduced at the highest dose of ACTH-(1
24) in long-standing diabetes; grooming was reduced only at the highest dose of
ACTH-(1-24), both in early and in long-standing diabetes. The fact that ACTH
induced penile erections (a centrally mediated effect) are practically absent
even a few days after streptozotocin injection suggests that diabetes mellitus
induced penile dysfunction occurs, at least in part, through central mechanisms,
and is not solely the consequence of peripheral nerve and vascular lesions.
PMID- 9639254
TI - The cholecystokinin-B receptor antagonist L-740,093 produces an insurmountable
antagonism of CCK-4 stimulated functional response in cells expressing the human
CCK-B receptor.
AB - A stable cell line expressing the human cholecystokinin-B receptor gene (hCCK
B.CHO) has been employed in an evaluation of the recently developed CCK-B
receptor antagonist L-740,093. L-740,093 exhibited high affinity (IC50 0.49 nM)
and selectivity (<50% displacement at CCK-A sites at 1 microM) for the human CCK
B receptor subtype as estimated from [125I]-CCK-8S displacement studies with
membranes prepared from hCCK-B.CHO cells. The elevation of intracellular free
Ca2+ in hCCK-B.CHO cells in response to stimulation with CCK-4 was used to
evaluate the antagonist activity of L-740,093 in vitro. L-740,093 potently (IC50
5.4 nM) antagonized the 30 nM CCK-4-stimulated Ca2+ mobilization in hCCK-B.CHO
cells. Further studies were performed to investigate the nature of the antagonist
activity of L-740,093. When tested at 10 nM L-740,093 produced a modest rightward
shift in the CCK-4 dose response curve, an effect which was accompanied by a
small reduction (13%) in the maximum response to CCK-4. In the presence of 30 nM
L-740,093 the maximum functional response to CCK-4 was further reduced by 45%
indicating that L-740,093 behaves as an insurmountable antagonist of the human
CCK-B receptor subtype.
PMID- 9639255
TI - Extracellular dopamine in the anterior nucleus accumbens is distinctly affected
by ventral tegmental area administration of cholecystokinin and apomorphine: data
from in vivo voltammetry.
AB - The interaction of cholecystokinin (CCK) and dopamine (DA) in the mesolimbic
system was investigated. The study focused on DAergic cells not containing
colocalized CCK projecting from the ventral tegmental area (VTA) to the anterior
nucleus accumbens (NA). Differential pulse voltammetry in pargyline pretreated
and anesthetized rats was used to measure extracellular DA in the anterior NA
following microinjection of apomorphine either alone or in combination with CCK
8s into the VTA. In agreement with an earlier study there was a dose-dependent
increase in the DA signal in the anterior NA after microinjection of CCK-8s into
the VTA. Apomorphine microinjected into the VTA produced a biphasic effect on
extracellular DA in the anterior NA with an increase from basal levels of
approximately 50% by 1 ng, whereas 10 ng was ineffective and 100 ng apomorphine
caused a slight decrease in the DA signal. Apomorphine (1 ng) microinjected
together with 1 ng CCK-8s produced an increase in the DA signal to approximately
180% of the baseline value, whereas the combination of 1 ng apomorphine and 100
ng CCK-8s was ineffective. When 100 ng apomorphine were microinjected in
combination with either 1 ng or 100 ng CCK-8s, the DA signal in the anterior NA
was unchanged. These results suggest that low doses of apomorphine injected into
the VTA synergistically influence the effects of CCK-8s on extracellular DA in
the anterior NA, whereas higher doses of apomorphine suppress the effect of CCK
8s on DAergic cells projecting to the anterior NA.
PMID- 9639256
TI - Expression and protective effects of urocortin in cardiac myocytes.
AB - Reverse transcription PCR showed that mRNA encoding the CRH-like molecule,
urocortin, is expressed in a rat cardiac myocyte cell line and in primary
cultures of cardiac myocytes. Identity of the amplified with the published
sequence was established by restriction mapping and direct sequencing. Expression
of urocortin mRNA was increased 12-18 h after thermal injury. Urocortin peptide
protected cardiac myocytes from cell death induced by hypoxia. The data suggest
that urocortin is an endogenous cardiac myocyte peptide which modulates the
cellular response to stress.
PMID- 9639257
TI - Opioids modulate the calcitonin gene-related peptide8-37-mediated hindpaw
withdrawal latency increase in thermally injured rats.
AB - The present study was performed to explore the modulatory potential of different
endogenous opioid systems on transmission of presumed nociceptive information at
the spinal cord level in thermally injured rats. Thermal injury was performed by
dipping the left paw into water 60 degrees C for 20 s. This induced a significant
bilateral decrease in hindpaw withdrawal latency HWL to pressure. Intrathecal
administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in
HWL in the thermally injured group and in the intact controls. The effect of
different opioid receptor antagonists on the increased latency to withdrawal
response induced by intrathecal injection of 10 nmol of CGRP8-37 was explored in
the thermally injured rats. The effect was reversed by intrathecal injection of
40 and 80 nmol of: b-funaltrexamine (mu opioid receptor antagonist) and
naltrindole (delta opioid receptor antagonist), but not by norbinaltorphimine
(kappa opioid receptor antagonist). The results of the present study show that
intrathecal CGRP8-37 increases hindpaw withdrawal latency in thermally injured
rats, an effect reduced by a mu as well as by a delta opioid receptor antagonist.
PMID- 9639258
TI - Increased concentrations of calcitonin gene-related peptide-like immunoreactivity
in rat brain and peripheral tissue after ischaemia: correlation to flap survival.
AB - The effects of experimentally induced ischaemia after free-flap surgery on
concentrations of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and
calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) were studied
in flap tissue and in different regions of the rat brain (striatum, hippocampus,
pituitary, hypothalamus, frontal and occipital cortex). Ten days after the
operation, CGRP-LI and NKA-LI were decreased in the ischaemic tissue but
increased in the surrounding tissue. In the brain, CGRP-LI was increased in five
of six regions analysed, with the exception of the striatum. SP-LI and NKA-LI
were increased in the pituitary and hippocampus, but decreased in other brain
regions. Changes of CGRP-LI in the brain correlated positively with the CGRP-LI
concentrations in the surrounding flap tissue and the CGRP-LI concentrations in
the ischaemic flap tissue with the extent of flap survival. The results of the
present study suggest that higher concentrations of CGRP-LI are related to tissue
survival and that endogenous CGRP has a regulatory effect in ischaemia.
PMID- 9639259
TI - Protein kinase C is involved in cholecystokinin octapeptide-induced proliferative
action in rat glioma C6 cells.
AB - Chotecystoknin octapeptide (CCK-8) has been shown to stimulate DNA synthesis in
rat glioma C6 cells by activation of CCKB type receptors. However, the signalling
pathways contributing to this proliferative action in C6 cells have not been
investigated thus far. This study demonstrated that stimulation of rat glioma C6
cells with CCK-8S resulted in activation of protein kinase C isozymes betaI,
betaII, gamma and zeta. The participation of protein kinase C in the CCK-8S
induced effect on C6 cell growth was demonstrated by measurement of [3H]thymidine
incorporation and estimation of cell number. The data indicate that CCK-8S
stimulates growth in rat glioma C6 cells by a protein kinase C-dependent
mechanism.
PMID- 9639260
TI - Identification of the spinal degradation products and inhibition of adenylate
cyclase by recombinant rat galanin message-associated peptide.
AB - In rat preprogalanin, galanin is C-terminally flanked by a 60 amino acid long
peptide: galanin message-associated peptide (GMAP). GMAP sequences in different
species show high degree of homology, suggesting a biological role. However, the
study of the physiological and pharmacological actions of this peptide have been
hampered by lack of availability of this large peptide, its fragments and well
characterized antibodies to GMAP. This study report the production of GMAP in
Escherichia coli and the use of the recombinant peptide to define its degradation
products in the spinal cord. The GMAP fragments formed upon incubation of GMAP
with membranes of lumbar spinal cord were identified by sequencing and were also
produced by solid phase synthesis for studies on second messenger systems.
Furthermore, the study demonstrates that GMAP inhibits forskolin stimulated
adenylate cyclase activity in a concentration dependent manner, while GMAP and
its synthetic fragments did not affect cGMP level.
PMID- 9639261
TI - Reduction of sensory and metabotropic glutamate receptor responses in the
thalamus by the novel metabotropic glutamate receptor-1-selective antagonist S-2
methyl-4-carboxy-phenylglycine.
AB - Previous work has shown that responses of thalamic neurons in vivo to the
metabotropic glutamate receptor agonists 1S,3R-aminocyclopentane-1,3
dicarboxylate and S-3,5-dihydroxyphenylglycine can be reduced by a variety of
phenylglycine antagonists. Responses of thalamic neurons to noxious thermal
somatosensory stimuli were reduced in parallel by these antagonists, indicating
that these responses are mediated by Group I metabotropic glutamate receptors
(i.e. metabotropic glutamate receptor-1 and/or metabotropic glutamate receptor
5), which are known to be linked to phosphoinositol phosphate hydrolysis. The
recent development of S-2-methyl-4-carboxyphenylglycine as an antagonist which is
highly selective for metabotropic glutamate receptor-1 compared to metabotropic
glutamate receptor-5 on human receptors expressed in AV-12 cells, now offers the
possibility of discriminating between these two receptor subtypes in order to
distinguish which is involved in thalamic responses. We have made recordings from
single somatosensory neurons in the thalamus of the rat, and find that S-2-methyl
4-carboxy-phenylglycine is able to reduce responses of neurons to 1S,3R
aminocyclopentane-1,3-dicarboxylate, S-3,5-dihydroxyphenylglycine, and noxious
stimuli without significant effect on responses to either N-methyl-D-aspartate or
(+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. These results suggest
that excitatory responses of thalamic neurons to 1S,3R-aminocyclopentane-1,3
dicarboxylate and S-3,5-dihydroxyphenylglycine may be mediated by metabotropic
glutamate receptor-1. Furthermore, the reduction of nociceptive responses by S-2
methyl-4-carboxy-phenylglycine indicates that metabotropic glutamate receptor-1
is involved in thalamic nociceptive processing and that such antagonists may have
analgesic properties.
PMID- 9639262
TI - Nociceptive stimulus induces release of endogenous beta-endorphin in the rat
brain.
AB - The hypothesis that the naturally occurring analgesic peptide, beta-endorphin, is
released in the brain in response to pain had never been directly validated. In
this study, we applied a brain microdialysis method for monitoring beta-endorphin
release in vivo, to test this hypothesis in the brains of conscious, freely
moving rats. Herein we first show that endogenous beta-endorphin can be measured
in vivo in the brain under physiological conditions. Upon induction of a
nociceptive stimulus by injection of formalin into the hind-paws of rats, the
extracellular levels of beta-endorphin in their arcuate nucleus increased by 88%,
corresponding to their nociceptive response. This direct evidence for the release
of endogenous beta-endorphin in the brain in response to nociceptive stimulus
indicates a possible mechanism for organisms to cope with pain.
PMID- 9639263
TI - Putative gap junctional communication between axon and regenerating Schwann cells
during mammalian peripheral nerve regeneration.
AB - Gap junctions are intercellular channels which mediate the traffic of ions and a
variety of molecular messengers between contiguous cells. Here, we report on the
possibility that atypical gap junctions develop between heterologous tissues,
such as regenerating nerve axons and Schwann cells, during peripheral nerve
regeneration in adult rats. After a complete transection and subsequent
regeneration in the rat sciatic nerve distal segment, a small scale gap junction
like structure was observed between the regenerating axons and adjoining Schwann
cells. Immunoelectron microscopy showed that one of the gap junctional proteins,
connexin32, was located at a small region of contact between the axon and Schwann
cells. Biocytin, a small molecular weight dye, was transported from regenerating
axons into adjoining Schwann cells. The present findings suggest that
regenerating axons communicate directly with adjacent Schwann cells through small
gap junctions, which may play a role in the mechanism of regeneration following
nerve transection.
PMID- 9639264
TI - Dopamine facilitates long-term depression of glutamatergic transmission in rat
prefrontal cortex.
AB - Using sharp-electrode intracellular recordings, we studied the dopaminergic
facilitation of synaptic plasticity in layer I-II afferents--layer V neuron
glutamatergic synapses in rat prefrontal cortex in vitro. Tetanic stimulation
(100 pulses at 50 Hz, four times at 0.1 Hz) to layer I-II afferents induced N
methyl-D-aspartate receptor-independent long-term depression (>40 min) of the
glutamatergic synapses when the stimulation was coupled with a bath-application
of dopamine. Tetanic stimulation alone did not induce lasting synaptic changes.
Dopamine application alone transiently depressed synaptic responses, which fully
recovered within 30 min. Pharmacological analyses with antagonists suggested that
dopamine action on either D1-like or D2-like receptors can facilitate the
induction of long-term depression. However, results with agonists were not fully
consistent with the antagonist results: while a D2 agonist mimicked the
facilitatory dopamine effect, D1 agonists failed to mimic the effect. We also
analysed the synaptic responses during tetanus and found that dopamine prolongs
membrane depolarization during high-frequency inputs. Postsynaptic membrane
depolarization is indeed critical for long-term depression induction in the
presence of dopamine, since postsynaptic hyperpolarization during tetanus blocked
the dopaminergic facilitation of long-term depression induction. Postsynaptic
injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetra-acetic acid
(100 mM in the electrode) also blocked long-term depression induction. Our
results show that dopamine lowers the threshold for long-term depression
induction in rat prefrontal glutamatergic transmission. A possible underlying
mechanism of this dopaminergic facilitation is the enhancement of postsynaptic
depolarization during tetanus by dopamine, which may increase the amount of Ca2+
entry from voltage-gated channels to the level sufficient for plasticity
induction.
PMID- 9639265
TI - Neurochemical features and synaptic connections of large physiologically
identified GABAergic cells in the rat frontal cortex.
AB - Physiological and morphological properties of large non-pyramidal cells
immunoreactive for cholecystokinin, parvalbumin or somatostatin were investigated
in vitro in the frontal cortex of 18-22-day-old rats. These three peptides were
expressed in separate populations including large cells. Cholecystokinin cells
and parvalbumin cells made boutons apposed to other cell bodies, but differed in
their firing patterns in response to depolarizing current pulses. Parvalbumin
cells belonged to fast-spiking cells. Parvalbumin fast-spiking cells also
included chandelier cells. In contrast, cholecystokinin cells were found to be
regular-spiking non-pyramidal cells or burst-spiking non-pyramidal cells with
bursting activity from hyperpolarized potentials (two or more spikes on slow
depolarizing humps). Large somatostatin cells belonged to the regular-spiking non
pyramidal category and featured wide or ascending axonal arbors (wide arbor cells
and Martinotti cells) which did not seem to be apposed to the somata so
frequently as large cholecystokinin and parvalbumin cells. For electron
microscopic observations, another population of eight immunohistochemically
uncharacterized non-pyramidal cells were selected: (i) five fast spiking cells
including one chandelier cell which are supposed to contain parvalbumin, and (ii)
three large regular-spiking non-pyramidal cells with terminals apposed to somata,
which are not considered to include somatostatin cells, but some of which may
belong to cholecystokinin cells. The fast-spiking cells other than a chandelier
cell and the large regular-spiking non-pyramidal cells made GABA-positive
synapses on somata (4% and 12% of the synapses in two small to medium fast
spiking cells, 22% and 35% of the synapses in two large fast-spiking cells, and
10%, 18% and 37% of the synapses in three large regular-spiking non-pyramidal
cells). A few terminals of the fast-spiking and regular-spiking non-pyramidal
cells innervated GABAergic cells. About 30% of the fast-spiking cell terminals
innervated spines, but few of the regular-spiking non-pyramidal cell terminals
did. A fast-spiking chandelier cell made GABA-positive synapses on GABA-negative
axon initial segments. These results suggest that large GABAergic cells are
heterogeneous in neuroactive substances, firing patterns and synaptic
connections, and that cortical cells receive heterogeneous GABAergic somatic
inputs.
PMID- 9639266
TI - Effects of lesions in the mesial frontal cortex on bimanual co-ordination in
monkeys.
AB - The hypothesis was tested that the mesial frontal cortex, including the
supplementary motor area, is engaged in bimanual co-ordination. Three monkeys,
trained in a well-co-ordinated bimanual pull-and-grasp task, were subjected to
unilateral or bilateral lesions of the mesial frontal cortex. With unilateral
lesions, the deficit consisted in a delay in movement initiation of the
contralateral arm. With a bilateral lesion, the deficit was more pronounced with
marked bilateral delays in movement onset and slowing in reaching. However, in
the three monkeys bimanual co-ordination at the moment of goal achievement
remained intact with an excellent temporal co-variation of the two limbs. In the
two unilateral cases, an adaptive strategy developed after a few sessions, either
by catching up during reaching with the limb contralateral to the lesion (monkey
M1) or by delaying movement initiation of the limb ipsilateral to the lesion
(monkey M2). This outcome is discussed in terms of Lashley's principle of motor
equivalence, i.e. invariant goal achievement with variable means. Bilateral
lesions led to a transient and near-total impairment in movement self-initiation
when all external cues were absent. It is concluded that in monkeys the mesial
frontal cortex does not play a crucial role in bimanual co-ordination but rather
in movement initiation, especially when sensory cues are absent.
PMID- 9639267
TI - Two visual areas located in the middle suprasylvian gyrus (cytoarchitectonic
field 7) of the cat's cortex.
AB - Neuronal properties and topographic organization of the middle suprasylvian gyrus
(cortical cytoarchitectonic field 7) were studied in three behaving cats with
painlessly fixed heads. Two main neuronal types were found within this field.
Type 1 neurons occupied the lateral part of the field and bordered representation
of directionally selective neurons of the lateral suprasylvian visual area by
vertical retinal meridian. Type 1 neurons had elongated and radially oriented
receptive fields located in the lower part of contralateral visual field. Type 1
neurons preferred stimuli moving out or to the centre of gaze at a low or
moderate speed, and many of them were depth selective. The responses were
enhanced by attention, oriented to the presented stimulus. Medial part of the
field 7 along the border with the area V3 was occupied by neurons with not
elongated receptive fields (type 2). These neurons preferred moderate and high
speeds of motion, and gratings of proper spatial frequency and orientation were
effective stimuli for them. Border between representations of type 2 and type 1
neurons coincided with projection of horizontal retinal meridian. At the rostral
and caudal borders of the field 7 abrupt changes of neuronal properties took
place. Neurons which abutted field 7 anteriorly and posteriorly resembled
hypercomplex cells and their small receptive fields were located in the central
part of the visual field. Topographical considerations and receptive field
properties allowed us to conclude that the medial part of the field 7 (included
type 2 neurons) is functionally equivalent to the area V4 in the cortex of
primates, while the lateral part (type 1 neurons) may correspond to the area V4T.
PMID- 9639268
TI - Differential expression of rat and human type I metabotropic glutamate receptor
splice variant messenger RNAs.
AB - The type I metabotropic glutamate receptor (mGlu1) messenger RNA and protein are
known to be widely expressed in rat brain, but knowledge of the regional
expression of splice variants other than mGlu1a is limited. Probes were designed
for in situ hybridization that specifically recognize each of the carboxy
terminal splice variants mGlu1a, -1b, -1c and -1d. The novel rat mGlu1d sequence
was obtained by polymerase chain reaction and the predicted protein is highly
homologous to the human sequence but contains both conservative and radical
substitutions and is slightly longer (912 vs 908 amino acids). Each rat mGlu1
splice variant messenger RNA was found in a unique expression pattern. The
messenger RNA encoding mGlu1a was abundant in cerebellar Purkinje cells and in
mitral and tufted cells of the olfactory bulb. Strong expression was also
detected in hippocampal interneurons, and neurons of the thalamus and substantia
nigra, while moderate expression was found in colliculi and cerebellar granule
cells. The mGlu1b messenger RNA was strongly expressed in Purkinje cells,
hippocampal pyramidal neurons, dentate gyrus granule cells and lateral septum,
and moderately expressed in striatal, superficial cortical and cerebellar granule
neurons. The mGlu1d messenger RNA was expressed in all regions where mGlu1a and
1b were detected; abundant in Purkinje cells, mitral and tufted cells, and
hippocampal principal neurons and interneurons, strong in thalamus and substantia
nigra, and moderate in lateral septum, cortex, striatum and colliculi. Human
mGlu1 splice variant expression in the cerebellum matched that found for the rat.
No specific signal was found with a probe capable of hybridizing to the rat
mGlu1c splice junction, although another probe designed against a more 3'
sequence of mGlu1c gave strong signals in the cerebellum and hippocampus, and
moderate signals in thalamus and colliculi. It is concluded that mGlu1d messenger
RNA is widely expressed, that mGlu1a and -1b messenger RNAs are expressed in
almost complementary patterns and that formation of the mGlu1c splice junction is
a rare event.
PMID- 9639269
TI - Neuroprotective activity of N-acetylaspartylglutamate in cultured cortical cells.
AB - The endogenous dipeptide, alpha-N-acetylaspartylglutamate behaves as a partial
agonist of N-methyl-D-aspartate receptors, but can also activate metabotropic
glutamate receptors, with a high degree of selectivity for the metabotropic
glutamate receptor 3 subtype. Knowing that agonists of group-II metabotropic
glutamate receptors (i.e. of mGlu2 and -3 receptors) are neuroprotective, we have
examined the neuroprotective activity of alpha-N-acetylaspartylglutamate in mixed
cultures of mouse cortical cells exposed to a toxic pulse with N-methyl-D
aspartate. Alpha-N-acetylaspartylglutamate co-applied with N-methyl-D-aspartate
was neuroprotective, but its action was insensitive to the selective group-II
metabotropic glutamate receptor antagonist, ethylglutamate. Protection was
instead antagonized by ethylglutamate when alpha-N-acetylaspartylglutamate was
applied to the cultures immediately after the N-methyl-D-aspartate pulse, a
condition in which there was no direct competition between alpha-N
acetylaspartylglutamate and N-methyl-D-aspartate at the level of N-methyl-D
aspartate receptors. alpha-N-acetylaspartylglutamate was highly neuroprotective
when transiently applied to pure cultures of cortical astrocytes and the
conditioned medium, collected 20 h later, was transferred to sister mixed
cultures challenged with N-methyl-D-aspartate. This particular form of
neuroprotection was attenuated or abolished when astrocytes where exposed to
alpha-N-acetylaspartylglutamate in the presence of the group-II metabotropic
glutamate receptor antagonists ethylglutamate or (2S, 1'S,2'S,3'R)-2-(2'-carboxy
3'-phenylcyclopropyl)glycine, but not in the presence of the N-methyl-D-aspartate
receptor antagonist, D-2-amino-5-phosphonopentanoate. These results indicate that
alpha-N-acetylaspartylglutamate induces neuroprotective effects in culture, which
are mediated, at least in part, by the activation of glial metabotropic glutamate
receptor 3 receptors.
PMID- 9639270
TI - Expression of HNK-1 carbohydrate and its binding protein, SBP-1, in apposing cell
surfaces in cerebral cortex and cerebellum.
AB - Sulfoglucuronyl carbohydrate is the terminal moiety of neolacto-oligosaccharides,
expressed on several glycoproteins of the immunoglobulin superfamily involved in
cell-cell recognition and on two glycolipids. Sulfoglucuronyl carbohydrate is
temporally and spatially regulated in the developing nervous system. It appears
to be involved in neural cell recognition and in cell adhesion processes through
its interaction with specific proteins on cell surfaces. Previously we have
characterized a specific sulfoglucuronyl carbohydrate-binding protein in rat
brain. Sulfoglucuronyl carbohydrate binding protein-1 is structurally similar to
a 30,000 mol. wt adhesive and neurite outgrowth promoting protein amphoterin
[Rauvala and Pihlaskari (1987) J. biol. Chem. 262, p. 16,625]. The pattern of
expression of sulfoglucuronyl carbohydrate binding protein-1 in developing rat
nervous system was studied to understand the significance of its interaction with
sulfoglucuronyl carbohydrate-bearing molecules. Biochemical analyses showed that
the expression of sulfoglucuronyl carbohydrate binding protein-1 was
developmentally regulated similarly to sulfoglucuronyl carbohydrate.
Immunocytochemical localization of sulfoglucuronyl carbohydrate binding protein-1
and sulfoglucuronyl carbohydrate was performed by bright-field and fluorescent
confocal laser scanning microscopy. In postnatal day 7 rat cerebellum,
sulfoglucuronyl carbohydrate binding protein-1 was primarily associated with
neurons of the external and internal granule cell layers. The sulfoglucuronyl
carbohydrate binding protein-1 immunoreactivity was absent in Purkinje cell
bodies and their dendrites in the molecular layer, as well as in Bergmann glial
fibres and in white matter. In contrast, sulfoglucuronyl carbohydrate (reactive
with HNK-1 antibody) was localized in processes surrounding granule neurons in
the internal granule cell layer. Sulfoglucuronyl carbohydrate was also expressed
in Purkinje neurons and their dendrites in the molecular layer and their axonal
processes in the white matter. To a lesser extent Bergmann glial fibres were also
positive for sulfoglucuronyl carbohydrate. In the cerebral cortex, at embryonic
day 21, sulfoglucuronyl carbohydrate binding protein-1 was mainly observed in
immature neurons of the cortical plate and subplate and dividing cells near the
ventricular zone. Whereas, sulfoglucuronyl carbohydrate was strongly expressed in
the fibres of the subplate and marginal zone. Sulfoglucuronyl carbohydrate was
also found in the processes surrounding the sulfoglucuronyl carbohydrate binding
protein-1-expressing neuronal cell bodies in the cortical plate and in
ventricular zone. The specific localization of sulfoglucuronyl carbohydrate
binding protein- in cerebellar granule neurons and neurons of the cerebral cortex
was also confirmed by immunocytochemistry of the dissociated tissue cell
cultures. The complementary localization of sulfoglucuronyl carbohydrate and
sulfoglucuronyl carbohydrate binding protein-1, both in cerebral cortex and
cerebellum, in apposing cellular structures indicate possible interaction between
the two and signalling during the process of cell migration and arrest of
migration.
PMID- 9639271
TI - Cerebellar circuitry is activated during convulsive episodes in the tottering
(tg/tg) mutant mouse.
AB - Tottering (tg) is an autosomal recessive mutation of the calcium channel alpha1A
subunit in the mouse that results in epileptic spike and wave discharges, mild
ataxia and paroxysmal episodes of involuntary spasms of the limbs, trunk and
face. These convulsions have been especially difficult to characterize because of
their unpredictable occurrence and lack of electroencephalographic correlates.
However, it is, in fact, possible to induce these convulsions, making this facet
of the tottering phenotype amenable to controlled experimentation for the first
time. Here, the neuroanatomical basis of the convulsions in tottering mice has
been identified using in situ hybridization for c-fos messenger RNA to chart
abnormal neuronal activity. Convulsion-induced c-fos messenger RNA expression was
most prominent in the cerebellum of convulsing tottering mice. Additionally,
cerebral cortex and principal cerebellar relay nuclei were also activated during
a convulsion. The c-fos activation in the cerebellum temporally preceded
expression in cerebral cortex, suggesting that cerebral cortex is not driving the
expression of convulsions. These results suggest that the cerebellum, a region
not classically associated with paroxysmal events, is important in the generation
and/or maintenance of the intermittent convulsions in tottering mutant mice.
PMID- 9639272
TI - A single pre-training glucose injection induces memory facilitation in rodents
performing various tasks: contribution of acidic fibroblast growth factor.
AB - Effects of a pre-training intraperitoneal glucose injection on learning and
memory were tested using two tasks: passive avoidance and Morris water maze. In
the former task, mice that had received glucose 2 h prior (but not 1, 3, or 5 h
prior) to a trial that combined acquisition with passive avoidance of foot shock
showed a significantly increased retention latency when tested 24 h later. Thus,
this effect was time-dependent, and it was also found to be dose-dependent by
further experiment. In contrast, 2-deoxy-D-glucose and fructose had no such
effect. In the Morris water maze task, glucose injection 2 or 3 h before a block
of trials enhanced the spatial memory performance of mice. These glucose-induced
memory-facilitation effects were abolished by an intracerebroventricular
injection of anti-acidic fibroblast growth factor antibody 30 min before the
glucose injection, suggesting a critical role for endogenous acidic fibroblast
growth factor in this facilitatory effect. Furthermore, continuous
intracerebroventricular infusion of acidic fibroblast growth factor in rats
significantly increased retention latency (when tested repeatedly on successive
days using a passive avoidance task). Our earlier studies demonstrated that brain
acidic fibroblast growth factor is produced in the ependymal cells of the
cerebroventricular system, and is released into the cerebrospinal fluid following
either a meal or a (intraperitoneal or intracerebroventricular) glucose
injection. This released acidic fibroblast growth factor also diffuses into the
brain parenchyma, and is taken up by neurons in the hippocampus, hypothalamus,
and elsewhere in the brain some 2 h after the meal or glucose injection. These
and the present findings indicate (i) that pre-training glucose injection
improves memory performance, and (ii) that acidic fibroblast growth factor,
especially by its action within the hippocampus, is involved in this enhancement
process.
PMID- 9639273
TI - Corticotropin-releasing hormone receptor (type I) antisense targeting reduces
anxiety.
AB - Two brain-derived corticotropin-releasing hormone receptors have been cloned,
termed corticotropin-releasing hormone receptors type I and type 2. Antisense
oligodeoxynucleotides targeted to the cloned rat and mouse corticotropin
releasing hormone receptors type I messenger RNA reduced the binding of the
natural ligand of the corticotropin-releasing hormone receptors type I and also
the release of adenocorticotrophic hormone in primary rat anterior pituitary
cells and in clonal mouse pituitary cells (AtT-20) by up to 60% in an application
time-dependent manner. Studies on intracellular uptake of fluorescence-labelled
oligodeoxynucleotides indicated a cytoplasmic accumulation starting within two to
four hours after application of oligodeoxynucleotides in vitro. In vivo,
antisense oligodeoxynucleotides infused intra-cerebroventricularly reduced
binding of radiolabelled corticotropin-releasing hormone receptors in central
sites of the rat brain. Anxiety induced by i.c.v. administration of corticotropin
releasing hormone was attenuated by corticotropin-releasing hormone receptors
type I antisense treatment as determined in the elevated plus maze and in the
novel open field test. The corticotropin-releasing hormone-induced behavioural
changes were absent in corticotropin-releasing hormone receptors type I antisense
pretreated animals. These results show that the selected antisense probes used
were able to suppress corticotropin-releasing hormone receptors type I function
in vitro as well as in vivo and suggest that the development of drugs blocking
this specific receptor might lead to a novel class of anxiolytics.
PMID- 9639274
TI - The role of alpha-2 receptors in the medial preoptic area in the regulation of
sleep-wakefulness and body temperature.
AB - The study was conducted on 48 free-moving male rats to find out the role of the
medial preoptic alpha2 receptors in the regulation of sleep and body temperature.
Recording electrodes for assessment of sleep-wakefulness, and injector cannulae
for injection of drugs in the medial preoptic area were chronically fixed on the
skulls of the animals. The noradrenergic fibres projecting to the medial preoptic
area were destroyed in 24 rats by administration of 6-hydroxydopamine at the
ventral noradrenergic bundle. Though arousal was produced in normal rats by the
injection of the alpha2 adrenergic agonist, clonidine, at the medial preoptic
area, it induced sedation in rats with noradrenergic fibre lesion. Clonidine did
not alter the rectal temperature in normal rats but it induced hypothermia in
lesioned rats. Injection of alpha2 antagonist, yohimbine, at the medial preoptic
area induced sleep in rats with intact noradrenergic fibres. However, the sleep
inducing effect of this drug was very much attenuated in the lesioned animals.
There was no significant change in body temperature, in both these groups of
animals, after yohimbine administration. The study indicates the role of
presynaptic alpha2 adrenergic receptors in arousal response and indirectly
supports the contention that the alpha1 postsynaptic receptors at the medial
preoptic area are involved in hypnogenesis. It also suggests that the thermal
changes induced by adrenergic system are mediated through alpha1 postsynaptic
receptors. But the thermal changes do not contribute towards the induced
alterations in sleep-wakefulness. It is proposed that there should be separate
sets of noradrenergic terminals for regulation of sleep and body temperature.
PMID- 9639275
TI - Galanin stimulates the N-methyl-D-aspartate receptor/nitric oxide/cyclic GMP
pathway in vivo in the rat ventral hippocampus.
AB - We investigated whether the neuropeptide galanin affects the nitric oxide
synthase/cyclic GMP pathway in rat hippocampus by measuring in vivo the
extracellular cyclic GMP levels during microdialysis. Galanin (2.5 and 3.5 nmol;
i.c.v.) dose-dependently raised the extracellular levels of cyclic GMP in the
ventral but not the dorsal hippocampus. The effect of 3.5 nmol galanin was
blocked by local application of tetrodotoxin and inhibited by the high-affinity
galanin antagonist M40 (galanin-[1-12]-Pro3-[Ala-Leu]2-Ala amide). The non
competitive N-methyl-D-aspartate receptor antagonist dizocilpine maleate (30
microM infused into the ventral hippocampus or 0.2 mg/kg, i.p.) and the
competitive one, 3-([R]-carboxypiperazin-4-yl)-propyl-phosphonic acid (50 microM
infused), but not local perfusion of the AMPA antagonist 6-nitro-7
sulphamoylbenzo(f)quinoxaline-2,3-dione (15 microM) abolished the galanin-evoked
cyclic GMP response in the hippocampus. Inhibitors of nitric oxide synthase, L
Arg(NO2)-OMe.HCl and 7-nitroindazole monosodium salt, applied locally, blocked
the galanin-induced increase in hippocampal extracellular cyclic GMP. This
increase was also prevented by local application of 1H-(1,2,4)oxadiazolo(4,3a)
quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase. The galanin
receptors mediating the rise in cyclic GMP reside outside the hippocampus, as
galanin (0.35-3 nmol) locally applied had no effect. The results provide in vivo
evidence that galanin stimulates the N-methyl-D-aspartate receptor/nitric oxide
synthase/cyclic GMP pathway in the ventral hippocampus, which may be of
importance in memory processes.
PMID- 9639276
TI - On the role of galanin in mediating spinal flexor reflex excitability in
inflammation.
AB - The effects of exogenous and endogenous galanin on spinal flexor reflex
excitability was evaluated in rats one to eight days after the induction of
inflammation by subcutaneous injection of carrageenan into the sural nerve
innervation area. In normal rats, electrical stimulation of C-fibres in the sural
nerve elicited a brisk reflex discharge. Conditioning stimulation of C-fibres
(1/s) generated a gradual increase in reflex magnitude (wind-up), which was
followed by a period of reflex hyperexcitability. Intrathecal galanin dose
dependently blocked reflex hyperexcitability induced by C-fibre conditioning
stimulation whereas i.t. M-35, a high-affinity galanin receptor antagonist,
moderately potentiated this effect. At one to three days after the injection of
carrageenen, when inflammation was at its peak, the magnitude of the reflex was
significantly increased and discharge duration became prolonged. However, wind-up
and reflex hyperexcitability were significantly reduced. Furthermore, reduced
reflex excitability during conditioning stimulation ("wind-down") and depression
of the reflex were sometimes present, which are rarely observed in normal rats.
Intrathecal galanin reduced hyperexcitability during inflammation, although its
potency was weaker than in normals. However, the galanin receptor antagonist M-35
strongly enhanced wind-up and reflex hyperexcitability, similarly as in normal
rats. The baseline flexor reflex, wind-up and C-fibre conditioning stimulation
induced facilitation were normalized four to eight days after carrageenan
injection when signs of inflammation were diminishing. Interestingly, intrathecal
galanin and M-35 failed to influence spinal excitability. The results suggest a
complex functional plasticity in the role of endogenous galanin in mediating
spinal excitability during inflammation. There appears to be an enhanced
endogenous inhibitory control by galanin on C-afferent input during the peak of
inflammation, which may explain the relative ineffectiveness of exogenous
galanin. During the recovery phase there may be a reduction in galanin receptors,
which may impair the action of endogenous and exogenous galanin. These results
further support the notion that galanin is an endogenous inhibitory peptide in
nociception.
PMID- 9639277
TI - Apposition of enkephalin- and neurotensin-immunoreactive neurons by serotonin
immunoreactive varicosities in the rat spinal cord.
AB - The descending serotonergic system provides a powerful inhibitory input to the
dorsal horn of the spinal cord. Little is known about the chemical identity of
the spinal neurons that the serotonergic system innervates, although spinal
enkephalinergic neurons are likely candidates. This study investigated the
apposition of serotonin-immunoreactive varicosities onto enkephalin- and
neurotensin-immunoreactive neurons in the rat lumbosacral spinal cord. Using a
double immunofluorescence technique, serotonin-immunoreactive varicosities were
observed to abut the soma or proximal dendrites of [Met]enkephalin- and
neurotensin-immunoreactive neurons. Nearly 75% of all [Met]enkephalin- and
neurotensin-immunoreactive neurons were apposed by serotonin-immunoreactive
varicosities in the marginal zone and dorsal gray commissure. In substantia
gelatinosa, approximately half of the [Met]enkephalin- and neurotensin
immunoreactive neurons were juxtaposed by serotonin-immunoreactive varicosities.
[Met]enkephalin-immunoreactive neurons also were bordered by serotonin
immunoreactive varicosities in the nucleus proprius (65%) and sacral
parasympathetic nucleus (75%). The results of this study suggest that the
descending serotonergic system mediates nociception via probable contacts with
intrinsic enkephalin and neurotensin spinal systems. The mode of action of spinal
serotonin on enkephalin and neurotensin neurons may be through "volume"
transmission vs synaptic or "wiring" transmission.
PMID- 9639278
TI - Reduced nicotinamide adenine dinucleotide phosphate diaphorase in the spinal cord
of dogs.
AB - The distribution of somatic, fibre-like and punctate, non-somatic reduced
nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity was
examined in dog spinal cord using horizontal, sagittal and transverse sections.
The morphological features of NADPH diaphorase exhibiting neurons divided into
six different neuronal types (N1-N6) were described and their laminar
distribution specified. Major cell groups were identified in the superficial
dorsal horn and around the central canal at all spinal levels, and in the
intermediolateral cell column at thoracic level. NADPH diaphorase exhibiting
neurons of the pericentral region were distributed in a thin subependymal cell
column containing longitudinally-arranged small bipolar neurons with processes
penetrating deeply into the intermediolateral cell column and/or running
rostrocaudally in the subependymal layer. The second pericentral cell column
located more laterally in lamina X contains large, intensely-stained NADPH
diaphorase exhibiting neurons with long dendrites radiating in the transverse
plane. Neurons of the sacral parasympathetic nucleus seen in segments S1-S3
exhibited prominent NADPH diaphorase activity accompanied by heavily-stained
fibres extending from Lissauer's tract through lamina I along the lateral edge of
the dorsal horn to lamina V. A massive dorsal gray commissure, with high NADPH
diaphorase activity, was found in segments S1-S3. At the same segmental level a
prominent group of moderately-stained motoneurons was detected in the
dorsolateral portion of the anterior horn. Fibre-like NADPH diaphorase activity
was found in the superficial dorsal horn and pericentral region in all segments
studied. Punctate, non-somatic NADPH diaphorase activity was detected in the
superficial dorsal horn, in the pericentral region all along the rostrocaudal
axis and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments
Th2-L2), nucleus Y (segments S1-S3), and the dorsal part of the dorsal gray
commissure (S1-S3). A schematic diagram documenting the segmental and laminar
distribution of NADPH diaphorase activity is given.
PMID- 9639279
TI - Identification of lamina V and VII interneurons presynaptic to adrenal
sympathetic preganglionic neurons in rats using a recombinant herpes simplex
virus type 1.
AB - Although indirect evidence suggests that the control of sympathetic preganglionic
neurons is mediated to a great extent through interneurons, little is known about
the location, morphology or neurotransmitter phenotype of such interneurons. This
limitation seriously impedes our understanding of spinal synaptic circuits
crucial to control of arterial pressure and other visceral functions. We used a
highly neurotropic, minimally cytopathic recombinant herpes simplex virus type-1
to study spinal "sympathetic" interneurons labelled by trans-synaptic transport
of the virus from the adrenal gland in rats. Approximately 120-320 infected
neurons/rat were identified by immunocytochemical detection of the viral antigen.
We distinguished between virus-infected preganglionic neurons and infected
interneurons by (i) their location within the spinal laminae, (ii) their size and
shape and (iii) the presence or absence of immunoreactivity for the acetylcholine
synthesizing enzyme, choline acetyltransferase, a marker of sympathetic
preganglionic neurons. Virus-labelled sympathetic preganglionic neurons were
found within the known spinal preganglionic nuclei. Non-cholinergic, virus
labelled neurons were located throughout lamina VII and in the ventral portion of
lamina V. These putative interneurons were found in the major spinal
preganglionic nuclei, usually intermingled with the preganglionic neurons.
Sometimes, they were located in clusters separate from the preganglionic neurons.
The interneurons were approximately 15 microm in diameter, smaller than the
average preganglionic neuron (diameter=25 microm), and had a few fine processes
emanating from them. These non-cholinergic interneurons constituted approximately
one-half of the population of virus-infected neurons. In summary, with the use of
a recombinant herpes simplex virus, we identified a large number of non
cholinergic interneurons close to, or intermingled with, adrenal sympathetic
preganglionic neurons. The neurotransmitter phenotype of these neurons remains to
be determined but they likely integrate much of the supraspinal and primary
afferent inputs to spinal preganglionic neurons that control arterial pressure
and other visceral functions.
PMID- 9639280
TI - Differential regulation of the cloned kappa and mu opioid receptors.
AB - To directly compare the regulation of the cloned kappa and mu opioid receptor, we
expressed them in the same cells, the mouse anterior pituitary cell line AtT-20.
The coupling of an endogenous somatostatin receptor to adenylyl cyclase and an
inward rectifier K+ current has been well characterized in these cells, enabling
us to do parallel studies comparing the regulation of both the kappa and the mu
receptor to this somatostatin receptor. We show that the kappa receptor readily
uncoupled from the K+ current and from adenylyl cyclase after a 1 h pretreatment
with agonist, as indicated by the loss in the ability of the agonist to induce a
functional response. The desensitization of the kappa receptor was homologous, as
the ability of somatostatin to mediate inhibition of adenylyl cyclase or
potentiation of the K+ current was not altered by kappa receptor desensitization.
The mu receptor uncoupled from the K+ current but not adenylyl cyclase after a 1
h pretreatment with agonist. Somatostatin was no longer able to potentiate the K+
current after mu receptor desensitization, thus this desensitization was
heterologous. Interestingly, pretreatment with a somatostatin agonist caused
uncoupling of the mu receptor but not the kappa receptor from the K+ current.
These results show that in the same cell line, after a 1 h pretreatment with
agonist, the kappa receptor displays homologous regulation, whereas the mu
receptor undergoes only a heterologous form of desensitization. mu receptor
desensitization may lead to the alterations of diverse downstream events, whereas
kappa receptor regulation apparently occurs at the level of the receptor itself.
Broad alterations of non-opioid systems by the mu receptor could be relevant to
the addictive properties of mu agonists. Comparison of kappa and mu receptor
regulation may help define the properties of the mu receptor which are important
in the development of addiction, tolerance, and withdrawal to opioid drugs. These
are the first studies to directly compare the coupling of the kappa and mu
receptors to two different effectors in the same mammalian expression system.
PMID- 9639281
TI - Pharmacological, molecular and functional characterization of vasoactive
intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide
receptors in the rat pineal gland.
AB - Melatonin secretion from the mammalian pineal gland is strongly stimulated by
noradrenaline and also by vasoactive intestinal polypeptide (VIP) and pituitary
adenylate cyclase-activating polypeptide (PACAP). Three types of receptors for
VIP and PACAP have been characterized so far: VIP1/PACAP receptors and VIP2/PACAP
receptors, which possess similar high affinities for VIP and PACAP, and PACAP1
receptors which exhibit a 100-1000-fold higher affinity for PACAP. The aim of the
present study was to characterize the receptor subtype(s) mediating the
stimulatory effects of VIP and PACAP on melatonin synthesis in the rat pineal
gland. Autoradiographic studies showed that PACAP and VIP were equally potent in
displacing binding of radioiodinated PACAP27 from pineal sections. Amplification
of pineal complementary DNAs by polymerase chain reaction using specific primers
for the different receptor subtypes revealed that all three receptor messenger
RNAs are expressed and that VIP1/PACAP receptor messenger RNA was predominant
over VIP2/PACAP receptor messenger RNA. In vitro, VIP and PACAP stimulated
melatonin synthesis with similar high potency and the effect of the two peptides
were not additive. The selective VIP1/PACAP receptor agonists [R16]chicken
secretin (1-25) and [K15, R16, L27]VIP(1-7)/growth hormone releasing factor(8-27)
were significantly more potent than the selective VIP2/PACAP receptor agonist RO
25-1553 in stimulating melatonin secretion. The stimulatory effects of VIP and
PACAP were similarly inhibited by the VIP1/PACAP antagonist [acetyl-His1, D-Phe2,
K15, R16, L27]VIP(3-7)/growth hormone releasing factor(8-27). These data strongly
suggest that VIP and PACAP exert a stimulatory effect on melatonin synthesis
mainly through activation of a pineal VIP1/PACAP receptor subtype.
PMID- 9639282
TI - Quantitative immunolocalization of mu opioid receptors: regulation by naltrexone.
AB - The present study utilized a newly developed quantitative immunohistochemical
assay to measure changes in mu opioid receptor abundance following chronic
administration of the opioid receptor antagonist naltrexone. These data were
compared with those obtained from mu receptor radioligand binding on adjacent
tissue sections, in order to determine whether the characteristic antagonist
induced increase in radioligand binding is due to an increase in the total number
of mu receptors and/or to an increase in the proportion of receptors that are in
an active binding conformation in the absence of a change in the total number of
receptors. Adult male Sprague-Dawley rats were administered naltrexone, 7-8 mg/kg
per day, or saline continuously for seven days by osmotic minipumps, after which
time their brains were processed for immunohistochemistry and receptor
autoradiography on adjacent fresh frozen tissue sections. Semiquantitative
immunohistochemistry was performed using a radiolabelled secondary antibody for
autoradiographic determination and a set of radioactive standards. Results
demonstrate an overall concordance between the distribution of mu opioid
receptors as measured by the two different methods with a few exceptions.
Following naltrexone administration, mu receptor immunoreactivity was
significantly higher in the amygdala, thalamus, hippocampus, and interpeduncular
nucleus as compared with the saline-treated control animals. [3H]D-Ala2,N-Me
Phe4,Gly-ol5-enkephalin binding to mu opioid receptors was significantly higher
in the globus pallidus, amygdala, thalamus, hypothalamus, hippocampus, substantia
nigra, ventral tegmental area, central gray, and interpeduncular nucleus of the
naltrexone-treated rats. These findings indicate that in some brain regions
chronic naltrexone exposure increases the total number of mu opioid receptors,
while in other regions there is an increase in the percent of active receptors
without an observable change in the total number of receptors. Quantitative
receptor immunodetection together with ligand autoradiography provides a new
approach for investigating the regulation of mu opioid receptors on tissue
sections.
PMID- 9639283
TI - Attenuation of 6-hydroxydopamine-induced dopaminergic nigrostriatal lesions in
superoxide dismutase transgenic mice.
AB - 6-Hydroxydopamine is a neurotoxin that produces degeneration of the nigrostriatal
dopaminergic pathway in rodents. Its toxicity is thought to involve the
generation of superoxide anion secondary to its autoxidation. To examine the
effects of the overexpression of Cu,Zn-superoxide dismutase activity on 6
hydroxydopamine-induced dopaminergic neuronal damage, we have measured the
effects of 6-hydroxydopamine on striatal and nigral dopamine transporters and
nigral tyrosine hydroxylase-immunoreactive neurons in Cu,Zn-superoxide dismutase
transgenic mice. Intracerebroventricular injection of 6-hydroxydopamine (50
microg) in non-transgenic mice produced reductions in the size of striatal area
and an enlargement of the cerebral ventricle on both sides of the brains of mice
killed two weeks after the injection. In addition, 6-hydroxydopamine caused
marked decreases in striatal and nigral [125I]RTI-121-labelled dopamine
transporters not only on the injected side but also on the non-injected side of
non-transgenic mice; this was associated with decreased cell number and size of
tyrosine hydroxylase-immunoreactive dopamine neurons in the substantia nigra pars
compacta on both sides in these mice. In contrast, superoxide dismutase
transgenic mice were protected against these neurotoxic effects of 6
hydroxydopamine, with the homozygous transgenic mice showing almost complete
protection. These results provide further support for a role of superoxide anion
in the toxic effects of 6-hydroxydopamine. They also provide further evidence
that reactive oxygen species may be the main determining factors in the
neurodegenerative effects of catecholamines.
PMID- 9639284
TI - Rat striatal adenosinergic modulation of ethanol-induced motor impairment:
possible role of striatal cyclic AMP.
AB - We have previously reported the involvement of the striatum in acute ethanol
induced motor incoordination and the striatal adenosinergic modulation of ethanol
induced motor incoordination through A1 receptor-mediated mechanism(s). The
present study, a continuation of our previous work, was carried out to
investigate the possible functional correlation between striatal cyclic AMP and
ethanol-induced motor incoordination, and its modulation by striatal adenosine in
Sprague-Dawley rats. Forskolin (0.1, 0.5 and 1.0 pmol), a known activator of
adenylate cyclase, significantly attenuated ethanol-induced motor incoordination
in a dose-dependent manner following its direct intrastriatal microinfusion.
Forskolin also antagonized the accentuating effect of intrastriatal N6
cyclohexyladenosine on ethanol-induced motor incoordination. These results
suggested that ethanol-induced motor incoordination might be functionally
correlated to a decrease in the striatal cyclic AMP levels and that the striatal
adenosine A1 receptors might modulate ethanol-induced motor incoordination
through cyclic AMP signaling mechanism(s). Further support to this hypothesis was
obtained by the actual measurement of the striatal cyclic AMP levels in the same
experimental conditions as in motor coordination studies using high-performance
liquid chromatography with fluoroscence detection. Regardless of the method
(focused microwave irradiation, cervical dislocation or decapitation into a dry
ice-ethanol mixture) used to kill the animals, a significant decrease in the
striatal cyclic AMP levels was observed due to ethanol. Intrastriatal adenosine
A1-selective agonist, N6-cyclohexyladenosine (24 ng), caused a further
significant decrease in the striatal cyclic AMP levels in the ethanol- but not in
the vehicle-treated animals. The further enhancement in the ethanol-induced
decrease in the striatal cyclic AMP levels by intrastriatal N6
cyclohexyladenosine, therefore, functionally correlated with the observed
potentiating effect of intrastriatal N6-cyclohexyladenosine on ethanol-induced
motor incoordination. The effects of intrastriatal N6-cyclohexyladenosine+ethanol
and of ethanol alone on the striatal cyclic AMP levels were blocked by
intrastriatal pertussis toxin (500 ng) pretreatment, indicating the involvement
of pertussis toxin-sensitive G-proteins (Gi, Go) and possibly of the adenosine A1
receptor coupled to the G-proteins in the striatum. Furthermore, ethanol alone
significantly decreased the basal as well as the cyclic AMP-stimulated catalytic
activities of the striatal cyclic AMP protein kinase, which were further reduced
by intrastriatal N6-cyclohexyladenosine. The results of the present study
therefore support an involvement of a cyclic AMP signaling pathway in the
striatal adenosinergic modulation of ethanol-induced motor incoordination at the
post-adenosine A1 receptor level.
PMID- 9639285
TI - Riluzole interacts with voltage-activated sodium and potassium currents in
cultured rat cortical neurons.
AB - The actions of the neuroprotective and anticonvulsant agent riluzole on voltage
activated currents were studied in primary cultures of rat cortical neurons by
using whole-cell patch-clamp recording techniques. Isolated Na+, Ca2+ and K+
currents were generated in these cells by depolarizing commands from a holding
potential of - 80 mV. Riluzole (10-300 microM) reversibly reduced in a dose
dependent manner the inward Na+ currents with an IC50 of 51 microM in all the
tested neurons (n=29). This drug also shifted the steady-state inactivation curve
of the sodium current towards more negative values (about 20mV, n=15) while it
did not change significantly the decay phase of the Na+ current. Furthermore,
riluzole (100 and 300 microM; n=5 and n=3, respectively) did not modulate the
inward Ca2+ currents evoked by depolarizing steps on cortical cells. An
additional concentration-dependent effect of riluzole was observed on the outward
potassium currents. In fact, while the amplitude of the peak of the outward
current (IA) was not changed significantly, the amplitude of the late component
of the outward K+ current (Iss) was markedly decreased during the perfusion of
riluzole (IC50=88 microM; n=16). It is concluded that riluzole modulates the Na+-
and the late K+-dependent currents in cortical neurons. Both phenomena may
explain, at least in part, the anticonvulsant and neuroprotective properties of
this compound.
PMID- 9639287
TI - Comparison of vesicular volume and quantal size in bovine chromaffin cells.
AB - Electrochemical measurements of vesicular content released were compared with the
morphometric measurements of vesicular size in bovine chromaffin cells. Cross
sectional vesicular diameters were determined from electron micrographs. Two
methods were used to determine the frequency histograms of "true" vesicular
diameters (i.e. diameters of the vesicles in the equatorial plane): (i) "peeling
off" method [Coupland R. E. (1968), Nature 217, 384-388], and (ii) summation of
individual probabilities of "true" vesicular diameters. Quantal size was
estimated from the area under the spontaneous current spike detected
electrochemically. The frequency histograms of "true" vesicular diameters are
found to be skewed (thus not well described by a Gaussian function) irrespective
of the method used to calculate them, as are the frequency histograms of the cube
roots of the quantal sizes. Furthermore, we also find that the frequency
histograms of electrochemical measurements (the cube roots of quantal sizes) have
lower skews and coefficients of variation than those of morphometric measurements
("true" vesicular diameters), with discrepancy being especially pronounced for
noradrenaline-secreting cells. Such a difference in both coefficients of
variation and skews suggests that the intravesicular catecholamine concentration
is not uniform, but that it is lower for vesicles of larger size. In conclusion a
variety of factors--vesicular volume, vesicular surface area to volume ratio,
binding capacity of chromogranin and/or ATP, likely determines the amount of
catecholamine stored in the vesicle.
PMID- 9639286
TI - Mu-opioid and GABA(B) receptors modulate different types of Ca2+ currents in rat
nodose ganglion neurons.
AB - Whole-cell patch-clamp recordings were obtained from nodose ganglion neurons
acutely dissociated from 10-30-day-old rats to characterize the Ca2+ channel
types that are modulated by GABA(B) and mu-opioid receptors. Five components of
high-threshold current were distinguished on the basis of their sensitivity to
blockade by omega-conotoxin GVIA, nifedipine, omega-agatoxin IVA and omega
conotoxin MVIIC. Administration of the mu-opioid agonist H-Tyr-D-Ala-Gly-Phe(N
Me)-Gly-ol (0.3-1 mM) or the GABA(B) agonist baclofen in saturating
concentrations suppressed high-threshold Ca2+ currents by 49.9+/-2.4% (n=69) and
18.7+/-2.1% (n=35), respectively. The inhibition by H-Tyr-D-Ala-Gly-Phe(N-Me)-Gly
ol exceeded that by baclofen in virtually all neurons that responded to both
agonists (67%), and occlusion experiments revealed that responses to mu-opioid
and GABA(B) receptor activation were not linearly additive. In addition,
administration of staurosporine, a non-selective inhibitor of protein kinase A
and C, did not affect the inhibitory responses to either agonist or prevent the
occlusion of baclofen-induced current inhibition by H-Tyr-D-Ala-Gly-Phe(N-Me)-Gly
ol. Blockade of N-type channels by omega-conotoxin GVIA eliminated current
suppression by baclofen in all cells tested (n=11). Mu-opioid-induced inhibition
in current was abolished by omega-conotoxin GVIA in 12 of 30 neurons tested, but
was only partially reduced in the remaining 18 neurons. In the latter cells
administration of omega-agatoxin IVA reduced, but did not eliminate the mu-opioid
sensitive current component that persisted after blockade of N-type channels.
This residual component of mu-opioid-sensitive current was blocked completely by
omega-conotoxin MVIIC in nine neurons, whereas responses to H-Tyr-D-Ala-Gly-Phe(N
Me)-Gly-ol were still recorded in the remaining cells after administration of
these Ca2+ channel toxins and nifedipine. Dihydropyridine-sensitive (L-type)
current was not affected by activation of mu-opioid or GABA(B) receptors in any
of the neurons. These data indicate that in nodose ganglion neurons mu-opioid
receptors are negatively coupled to N-, P- and Q-type channels as well as to a
fourth, unidentified toxin-resistant Ca2+ channel. In contrast, GABA(B) receptors
are coupled only to N-type channels. Furthermore, the results do not support a
role for either protein kinase C or A in the modulatory pathway(s) coupling mu
opioid and GABA(B) receptors to Ca2+ channels, but rather lend credence to the
notion that the signalling mechanisms utilized by these two receptors might
simply compete for inhibitory control of a common pool of N-type channels.
PMID- 9639288
TI - Activity-dependent regulation of dopamine content in the olfactory bulbs of naris
occluded rats.
AB - Several lines of evidence strongly suggest that reduced olfactory nerve activity
results in decreased bulb dopamine content. In the present study, high
performance liquid chromatography with electrochemical detection was used to
assess catecholamine levels in bulbs from postnatal day 60 rats that had
undergone either unilateral naris cautery or a sham surgery on day 30. Thirty
days of odor deprivation dramatically reduced dopamine and dihydroxyphenylacetic
acid levels in functionally-deprived bulbs (ipsilateral to occluded nares) as
compared to contralateral controls, while norepinephrine and
dihydroxyphenylglycol levels were unchanged. The loss of dopamine was more severe
in medial as compared to lateral aspects of experimental bulbs, while the loss of
dihydroxyphenylacetic acid was similar on the two sides. To test directly the
hypothesis that afferent activity regulates dopamine and dihydroxyphenylacetic
acid content, 1 h of high frequency tetanic nerve stimulation was provided to the
rostral-medial olfactory nerve layer in deprived olfactory bulbs, and
catecholamine levels were assessed from 6 to 192 h later. Partial and temporary
recovery of dopamine was observed in medial aspects of the bulb when rats were
examined 96 h later, while consistent recovery of dihydroxyphenylacetic acid
content was not apparent. These data corroborate evidence that olfactory nerve
activity is a potent regulator of bulb dopamine and indicate that continued
afferent input is necessary to maintain dopamine levels.
PMID- 9639289
TI - Modulation of gamma-aminobutyric acid (GABA) receptors and the feeding response
by neurosteroids in Hydra vulgaris.
AB - Gamma-Aminobutyric acid (GABA) receptors are present in membrane preparations
from Hydra vulgaris, one of the most primitive organisms with a nervous system.
These receptors are sensitive to muscimol and benzodiazepines and appear to be
important in the regulation of the feeding response. The effects of
neurosteroids, general anaesthetics, and GABA antagonists on GABA(A) receptors in
membranes prepared from Hydra and on the feeding response have now been
investigated. The neurosteroids tetrahydroprogesterone and
tetrahydrodeoxycorticosterone increased [3H]GABA binding to hydra membranes with
nanomolar potency (EC50, 141+/-11 and 623+/-36 nM, respectively) and high
efficacy (maximal increase 79+/-6.5 and 62+/-4%, respectively), whereas the 3beta
hydroxy epimer of tetrahydroprogesterone was ineffective. The benzodiazepine
receptor ligands diazepam (100 microM), clonazepam (100 microM) and abecarnil (30
microM) enhanced [3H]GABA binding to Hydra membranes by 22, 20 and 24%,
respectively; effects abolished by the specific benzodiazepine antagonist
flumazenil (100 microM). On the contrary, the peripheral benzodiazepine receptor
ligand 4'chlorodiazepam failed to affect [3H]GABA binding to Hydra membranes. The
general anaesthetics propofol and alphaxalone similarly increased (+38% and +30%
respectively) [3H]GABA binding. Moreover, [3H]GABA binding to Hydra membranes was
completely inhibited by the GABA(A) receptor antagonist SR 95531, whereas
bicuculline was without effect. The modulation of GABA(A) receptors in vitro by
these various drugs correlated with their effects on the glutathione-induced
feeding response in the living animals. Tetrahydroprogesterone and
tetrahydrodeoxy-corticosterone (1 to 10 microM) prolonged, in a dose-dependent
manner, the duration of mouth opening induced by 10 microM glutathione, with
maximal effects of +33 and +29%, respectively, apparent at 10 microM
neurosteroid. Alphaxalone (10 microM) similarly increased (+33%) the effect of
glutathione. The effects of steroids on the feeding response were inhibited by SR
95531 in a dose-dependent manner; t-butylbyclophosphorothyonate (1 microM), a
specific Cl- channel blocker, which per se, like picrotoxin but not bicuculline,
shortened the duration of the response, also counteracted the steroids effects at
1 microM. These results suggest that the modulation of GABA(A) receptors by
steroids is an ancient characteristic of the animal kingdom and that the
pharmacological properties of these receptors have been highly conserved through
evolution.
PMID- 9639290
TI - Differential effect of protein kinase inhibitors on calcium-dependent and calcium
independent [14C]GABA release from rat brain synaptosomes.
AB - Rat brain synaptosomes were isolated to study the effects of protein kinase
inhibitors (sphingosine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
dihydrochloride, N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide,
staurosporine) on Ca2+-dependent and Ca2+-independent [14C]GABA release. The Ca2+
dependent [14C]GABA release was stimulated by depolarization with a K+-channel
blocker, 4-aminopyridine, or high K+ concentration. It has been shown that 4
aminopyridine-evoked [14C]GABA release strongly depends on extracellular Ca2+
while K+-evoked [14C]GABA release only partly decreases in the absence of
calcium. The substitution of sodium by choline in Ca2+-free medium completely
abolished Ca2+-independent part of K+-evoked [14C]GABA release. So the main
effect of 4-aminopyridine is the Ca2+-dependent one while high K+ is able to
evoke [14C]GABA release in both a Ca2+-dependent and Na+-dependent manner. In
experiments with protein kinase inhibitors, 4-aminopyridine and high K+
concentration were used to study the Ca2+-dependent and the Ca2+-independent
[14C]GABA release, respectively. In addition, the Ca2+-independent [14C]GABA
release was studied using alpha-latrotoxin as a tool. Pretreatment of
synaptosomes with protein kinase inhibitors tested, except of 1-(5
isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, resulted in a marked
inhibition of 4-aminopyridine-stimulated Ca2+-dependent [14C]GABA release. The
inhibitory effects of N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide and
staurosporine on [14C]GABA release were not due to their effects on 4
aminopyridine-promoted 45Ca2+ influx into synaptosomes. Only sphingosine (100
microM) reduced the 45Ca2+ influx. All the inhibitors investigated were
absolutely ineffective in blocking the Ca2+-independent [14C]GABA release
stimulated by alpha-latrotoxin. Three of them, except for sphingosine, did not
affect the Ca2+-independent [14C]GABA release stimulated by high potassium. The
inhibitory effect of sphingosine was equal to 30%. Thus, if [14C]GABA release
occurred in a Ca2+-independent manner irrespective of whether alpha-latrotoxin or
high K+ stimulated this process, it was not inhibited by the drugs decreased the
Ca2+-dependent [14C] GABA release. Given the above points it is therefore not
unreasonable to assume that the absence of Ca2+ in the extracellular medium
created the conditions in which the activation of neurotransmitter release was
not accompanied by Ca2+-dependent dephosphorylation of neuronal phosphoproteins,
and as a consequence the regulation of exocytotic process was modulated so that
the inhibition of protein kinases did not disturb the exocytosis.
PMID- 9639291
TI - FDG accumulation and tumor biology.
AB - The tumoral uptake of fluorine-18-deoxyglucose (FDG) is based upon enhanced
glycolysis. Following injection, FDG is phosphorylated and trapped
intracellularly. An important mechanism to transport FDG into the transformed
cell is based upon the action of glucose transporter proteins; furthermore,
highly active hexokinase bound to tumor mitochondria helps to trap FDG into the
cell. In addition, enhanced FDG uptake may be due to relative hypoxia in tumor
masses, which activates the anaerobic glycolytic pathway. In spite of these
processes, FDG uptake is relatively aspecific since all living cells need
glucose. Clinical use is therefore recommended in carefully selected patients.
PMID- 9639292
TI - Electrophysiological study, biodistribution in mice, and preliminary PET
evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane
(18F-MEM): a potential radioligand for mapping the NMDA-receptor complex.
AB - The effect of the fluorinated memantine derivative and NMDA receptor antagonist,
1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion
channel was studied by patch clamp recording. The results showed that 19F-MEM is
a moderate NMDA receptor channel blocker. A procedure for the routine preparation
of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction
sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1
[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl- 5-methyl-adamantane
and the subsequent cleavage of the BOC-protecting group using aqueous HCI. The
18F-MEM was obtained in 22 +/- 7% radiochemical yield (decay-corrected to EOB) in
a total synthesis time including HPLC purification of 90 min. A biodistribution
study after i.v. injection of 18F-MEM in mice showed a fast clearance of
radioactivity from blood and relatively high initial uptake in the kidney and in
the lung, which gradually decreased with time. The brain uptake was high (up to
3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10,
6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation
of the radioactivity in the mouse brain was consistent with the known
distribution of the PCP recognition site. Preliminary PET evaluation of the
radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention
in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich
regions (frontal cortex, striata, and temporal cortex). Delineation of the
hippocampus, a region known to contain a high density of NMDA receptors, was not
possible owing to the resolution of the PET tomograph. The regional brain uptake
of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801,
indicating competition for the same binding sites. In a preliminary experiment,
haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding
of 18F-MEM from the brain regions examined, suggesting that binding was also
occurring to the sigma recognition sites.
PMID- 9639293
TI - Exploration of the dopamine transporter: in vitro and in vivo characterization of
a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3
iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-m ethylph enyl)nortropane (PE2I).
AB - For the diagnosis and follow-up of neurodegenerative diseases, many cocaine
derivatives have been proposed as radioligands to explore the dopamine
transporter. As none of them have all the criteria of specificity and kinetics
for human use, we have developed a new derivative, (E)-N-(3-iodoprop-2-enyl)
2beta-carbomethoxy-3beta-(4'-methy lphenyl)nortropane (PE2I), which displays
promising properties. We report the characterization of PE2I in vitro on rat
striatal membranes and in vivo in rats and in monkeys. PE2I had a high affinity
(Kd = 0.09 +/- 0.01 nM) and high specificity for the dopamine transporter. In
rats we observed a high accumulation in the striatum; by contrast, a very low
fixation was measured in the cortex. Moreover, a preinjection of a saturating
dose of GBR 12909 prevented the striatal accumulation of PE2I by 74%. These
results confirmed the specificity of PE2I for the dopamine transporter. In vivo
in monkeys, SPECT studies showed a high accumulation in striatum. Moreover, an
equilibrium state was obtained 1 h after injection. PE2I seemed to be the most
promising ligand for the dopamine transporter exploration by SPECT using a single
day protocol.
PMID- 9639294
TI - Synthesis and characterization of a 11C-labelled derivative of S12968: an attempt
to image in vivo brain calcium channels.
AB - [11C]S11568 (3-ethyl-5-methyl 2-[2-(2-aminoethoxy)ethoxymethyl]-4-(2,3
dichlorophenyl)-6-methyl- 1,4-dihydropyridine-3,5-dicarboxylate) is a powerful
ligand for the visualization of the cardiac calcium channel in vivo using PET.
The aim of the present study was to synthesize a lipophilic, nonionized
derivative of S11568 to facilitate its penetration into the brain. To increase
the lipophilicity and to remove simultaneously the ionic nature of our ligand,
the N-tert-butoxycarbonyl (N-Boc) derivative of S11568 was synthesized. An IC50
value of 1.7 nM for this derivative confirmed that both the affinity and
selectivity for the calcium channel was unaltered by this chemical modification
(S11568 with IC50 value of 9.9 nM). The biologically more active enantiomer of
S11568, the levogyre isomer S12968, was labelled with 11C using [11C]iodomethane.
The lipophilicity of the N-Boc derivative was increased by a factor of three to
four when compared to the parent compound (as determined by the measurement of
the octanol/buffer partition coefficients). In vivo, this derivative slightly
crosses the blood-brain barrier, as demonstrated by a 4-fold increase (with
respect to the parent compound S12968) of the radioactivity in the brain using
the 11C-labelled N-Boc S12968. This uptake remained too low to be suitable for
imaging calcium channels.
PMID- 9639295
TI - High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a
fluoro analog of WAY-100635.
AB - No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2
pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of
the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by
microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis.
Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a
semipreparative HPLC C18 column. After Sep-Pak formulation, the
radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about
70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of
the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF
was studied with PET on fluothane-anesthetized cats. Following intravenous
injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the
hippocampus and cerebral cortex. Low levels of radioactivity were observed in
cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum
ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked
by prior administration of reference WAY-100635, demonstrating the specificity of
the ligand.
PMID- 9639296
TI - Blocking [211At]astatide accumulation in normal tissues: preliminary evaluation
of seven potential compounds.
AB - Normal tissue accumulation of 211At must be minimized during targeted
radiotherapy with 211At-labeled compounds. Therefore, we investigated the ability
of seven compounds to block normal organ uptake of [211At]astatide in mice:
potassium iodide, sodium thiocyanate, sodium perchlorate, sodium periodate,
cysteine, 2,3-dimercapto-1-propanesulfonic acid, and meso-2,3-dimercaptosuccinic
acid. The monovalent anions I-, SCN-, and ClO4- reduced 211At uptake in stomach
and thyroid, while thiocyanate and cysteine were the only compounds to
significantly reduce activity levels in lungs and spleen. This study suggests
that blocking agents may help reduce normal organ radiation doses in
endoradiotherapeutic procedures with 211At-labeled radiopharmaceuticals.
PMID- 9639297
TI - Radiosynthesis and quality assurance of 5-[124I]Iodo-2'-deoxyuridine for
functional PET imaging of cell proliferation.
AB - 5-[124I]Iodo-2'-deoxyuridine ([124I]IUdR) was routinely produced by direct
electrophilic labelling of 2'-deoxyuridine with 124I of high specific activity
(12 Ci/micromol) in an Iodogen-coated ReactiVial, followed by purification on a
Sep-Pak C-18 cartridge. The radiochemical purity was determined by TLC on a
Silicagel-60 plate and by reverse-phase HPLC on a RP-18 column. Based upon 45
syntheses, the yield ranged from 45% to 65%. The radiochemical impurity of
[124I]IUdR was determined at 2.9% by TLC (mainly iodate) and 4.3% by HPLC. The
chemical stability of the solvated formulation allowed a time window of 2 days
following end of synthesis (EOS) for chemical application, based upon the
required 95% radiochemical purity grade of [124I]IUdR. The labelled compound was
routinely used for the clinical determination of cell proliferation in glioma
patients by positron emission tomography.
PMID- 9639298
TI - Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex
virus thymidine kinase.
AB - Assessment of suicide enzyme activity would have considerable impact on the
planning and the individualization of suicide gene therapy of malignant tumors.
This may be done by determining the pharmacokinetics of specific substrates. We
generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after
transfection with a retroviral vector bearing the herpes simplex virus thymidine
kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were
performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell
line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and
phosphorylation than control cells, whereas in wild-type MCF7 cells no
phosphorylated GCV was detected. In bystander experiments the total GCV uptake
was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of
GCV correlated closely with the growth inhibition (r = 0.92). Therefore, the
accumulation of specific substrates may serve as an indicator of the HSV-tk
activity and of therapy outcome. Inhibition and competition experiments
demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake
and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the
nucleoside transport systems or for HSV-tk. This may be the limiting factor for
therapy success, necessitating the search for better substrates of HSV-tk.
PMID- 9639299
TI - Intracellular metabolism of 99mTc-d,l-HMPAO in vitro: a basic approach for
understanding the hyperfixation mechanism in damaged brain.
AB - The mechanism of technetium-99m-labeled d,l-hexamethylpropylene amine oxime
(99mTc-HMPAO) hyperfixation in damaged brain was elucidated using in vitro
metabolic studies. Among the subcellular fractions of mouse brain homogenate, the
mitochondrial fraction showed dominant metabolic activity with respect to 99mTc
HMPAO, followed by the cytosolic fraction. The metabolic activity of the
mitochondrial fraction was enhanced by heat and detergent treatment, being
proportional to the leakage of thiol (SH) compound(s) from the granules. The
leaked SH compound(s) had a higher metabolic activity than glutathione, a well
known reductant in cells. 99mTc-HMPAO might be metabolized by mitochondrial SH
compound(s) exhibiting strong reductant activity, and hyperfixation might be an
indication of mitochondrial damage of the brain.
PMID- 9639300
TI - Cellular distribution of 111In-LDTPA galactose BSA in normal and
asialoglycoprotein receptor-deficient mouse liver.
AB - 111In-LDTPA galactose BSA (bovine serum albumin) was used to evaluate the
asialoglycoprotein receptor (ASGPR) system in both normal and ASGPR-deficient
mice. The radiolabeled glycoprotein had complete liver uptake in both normal and
ASGPR-deficient mice. Metabolism and hepatic cell-type distribution studies were
performed. The normal mouse excreted greater than 60% of the hepatic activity,
while the ASGPR-deficient mouse excreted less than 40% of the hepatic activity.
111In-LDTPA galactose BSA was metabolized to 111In-LDTPA-L-lysine in both mouse
types. Normal mice showed 70% of the radioactivity in the hepatocyte, whereas the
homozygous ASGPR-deficient mouse had equal activity in the hepatocyte and the
hepatic endothelial cell.
PMID- 9639301
TI - Similarities in the biodistribution of iodine-labeled anti-Tac single-chain
disulfide-stabilized Fv fragment and anti-Tac disulfide-stabilized Fv fragment.
AB - We evaluated the biodistribution and pharmacokinetics of two different iodine
labeled Fv fragments of anti-Tac monoclonal antibody (MAb) in normal and tumor
bearing nude mice. One was a disulfide-stabilized Fv fragment (dsFv), and the
other was a single-chain disulfide-stabilized Fv fragment (scdsFv). The scdsFv is
a newly developed type of Fv fragment superior to the dsFv in which the VH and VL
are linked by covalent bonds through a spacer arm and by an internal disulfide
bond. These modifications increase the yield of scdsFv. Both reagents recognize
the alpha subunit of the interleukin-2 receptor (IL-2Ralpha). The biodistribution
of the Fv fragments was evaluated in normal mice co-injected with 50 mg of L
lysine and in a no-lysine control group. Biodistribution was also evaluated in
nude mice bearing subcutaneous tumor xenografts derived from IL-2Ralpha-positive
ATAC4 cells and receptor-negative A431 cells. These mice were co-injected with
125I-labeled anti-Tac scdsFv (6 microCi/0.7 microg) and 131I-labeled anti-Tac
dsFv (2 microCi/0.7 microg) or with 131I-labeled anti-Tac scdsFv (6 microCi/0.7
microg) and 125I-labeled anti-Tac dsFv (4 microCi/0.7 microg). The
biodistribution of 125I-labeled anti-Tac scdsFv and 131I-labeled anti-Tac dsFv
was very similar in all organs and the tumors. The renal uptake of both reagents
was blocked effectively (<93%) and similarly by lysine. The scdsFv cleared
slightly faster from the circulation than did the dsFv because there were more
aggregates of dsFv than of scdsFv (3% vs. 1%, respectively). The scdsFv-to-dsFv
ratio ranged from 0.79 to 1.20 in all organs at all time points we examined. In
conclusion, the first biodistribution study of an scdsFv molecule shows that the
scdsFv had a biodistribution very similar to that of the dsFv and seems to be a
good alternative to the dsFv because of its higher production yield.
PMID- 9639302
TI - Human polyclonal immunoglobulin labelled with technetium-99m via NHS-MAG3: a
comparison of radiochemical behavior and biological efficacy with other labelling
methods.
AB - The aim of this study was to evaluate the radiochemical behavior, biological
distribution, and localization in infection sites in mice of a human polyclonal
immunoglobulin (HIG) labelled with 99mTc by a novel MAG3-labelling method. The
resulting [99mTc]MAG3-HIG was compared with [99mTc]HIG preparations radiolabelled
directly via 2-mercaptoethanol (2-Me) or stannous ion (Sn) reduction and
indirectly via 2-iminothiolane (2-Im) conjugation. All preparations showed
similar UV and radioactivity HPLC profile to that of native HIG except for 2-Im
HIG, which showed aggregates. The stabilities of the label to challenge with
cysteine were similar for all the preparations. By nondenaturing SDS-PAGE, all
preparations other than MAG3-HIG showed evidence of lower molecular weight
fragments. The tissue distribution 4 and 24 h after intravenous administration of
the four preparations were compared in mice previously administered with an
isolate of Staphylococcus aureus in one thigh. The pharmacokinetics varied among
the different preparations. When prepared via 2-Me, Sn, and 2-Im, both blood
clearance and urinary excretion were faster than that of labelled MAG3-HIG. The
absolute uptake in the infected thigh at 24 h was significantly higher for HIG
labelled via MAG3 and 2-Me vs. the remaining methods. The infected thigh/normal
thigh radioactivity ratios were similar at both time points for labelled HIG
prepared via 2-Me, 2-Im, and NHS-MAG, methods but was significantly lower at 24 h
for HIG prepared via Sn. The radioactive HPLC profiles of serum at 4 and 24 h
were similar to that of the radiolabelled injectates. Based on these data we
conclude that each radiolabelled HIG preparation studied showed increased
localization in infectious foci although [99Tc]MAG3-HIG showed superior
radiochemical and biological characteristics under the conditions of this
investigation.
PMID- 9639303
TI - Toxicity, mutagenicity, and behavioral effects of beta-CIT, a ligand for dopamine
transporter exploration by SPECT.
AB - The cocaine analog beta-CIT is one of the most used compounds for SPET
examination of the dopamine transporter in drug abuse and Parkinson's disease.
However, the toxicity of this agent has not yet been studied. We report here
acute toxicity, mutagenicity, and effect on locomotor activity of beta-CIT. Acute
toxicity experiments were performed in mice and rats. The LD50 values were about
20 mg and 5 mg for mice and rats, respectively. There was no sex difference. The
mutagenicity was evaluated using the Ames' test. No mutagenic effect was observed
for beta-CIT. Effects on locomotor activity were measured in mice using the open
field test. beta-CIT increased locomotion (+65%) when injected at a dose of 0.312
mg/kg; the maximal increase (+205%) was observed at a dose of 1.25 mg/kg; at
higher doses, the effect was decreased slightly. These pharmacological findings
are in agreement with an inhibitory effect of beta-CIT at the dopamine
transporter. We conclude that with no mutagenic effects and LD50 more than 6
orders of magnitude higher than the routinely used doses in PET or SPET, it can
be assumed that beta-CIT can be safely used as a radioligand in humans.
PMID- 9639304
TI - Synthesis, estrogen receptor binding, and tissue distribution of a new
iodovinylestradiol derivative (17alpha,20E)-21-[123I]Iodo-11beta-nitrato-19-norp
regna-1,3,5 (10),20-tetraene-3,17-diol (E-[123I]NIVE).
AB - We have synthesized and evaluated E-11beta-nitrato-17alpha-iodovinylestradiol (E
NIVE; E-3c) and its 123I-labelled form, as a new potential radioligand for
imaging of estrogen receptor (ER)-positive human breast tumors. E-[123I]NIVE was
prepared by stereospecific iododestannylation of the E-tri-n-butylstannylvinyl
precursor (E-2c), obtained from reaction of 11beta-nitrato-estrone (8) with E
tributylstannylvinyllithium. In competitive binding studies, E-NIVE proved to
have high binding affinity for both the rat and the human ER (Ki 280-730 pM),
without significant binding to human sex hormone binding globulin. Distribution
studies in normal and mammary tumor-bearing rats showed specific ER-mediated
uptake of E-[123I]NIVE in the estrogen target tissues, i.e., uterus, ovaries,
pituitary, and hypothalamus, but not in the mammary tumors. Selective retention
in these target tissues, including tumor tissue, resulted in significant
increases over time for the target tissue-to-muscle uptake ratios, but not for
the target tissue-to-fat uptake ratios. The tumor-to-fat uptake ratio even
appeared constantly below 1. In the primary estrogen target tissues, E-[123I]NIVE
displayed high specific ER-mediated uptake and retention, which resulted in
moderate target-to-nontarget tissue uptake ratios. In contrast, in tumor tissue,
E-[123I]NIVE uptake appeared to be rather low and not ER-specific. As a
consequence, E-[123I]NIVE appears to be a less favorable radioligand for ER
imaging in breast cancer than the previously studied stereoisomers of 11beta
methoxy-17alpha-[123I]iodovinylestradiol (E- and Z-[123I]MIVE; [123I]E- and
[123I]Z-3b).
PMID- 9639305
TI - Monte Carlo-assisted voxel source kernel method (MAVSK) for internal beta
dosimetry.
AB - A method is described for the determination of patient-specific organ beta doses
given a known cumulated internal radioactivity distribution. A voxel source
kernel for 90Y analogous to the point source function was simulated. Dose to each
organ of interest could then be estimated by convolving the voxel source kernel
with the patient's 3-D volume with known radioactivity assigned to each voxel.
The dose calculation on eight organs took less than 1 min per patient using a Sun
Sparc10 workstation.
PMID- 9639306
TI - Comparison of the kit performance of three 99mTc myocardial perfusion agents.
PMID- 9639307
TI - Physical mapping of chromosomes VII and XV of Saccharomyces cerevisiae at 3.5 kb
average resolution to allow their complete sequencing.
AB - The high resolution complete physical maps of chromosomes VII and XV were
constructed to form the basis for sequencing these chromosomes as part of the
European systematic sequencing programme of the yeast genome, using a unique
cosmid library from strain FY1679, and an original top-down mapping strategy
involving I-Sce I chromosome fragmentation. A total of 138 and 196 cosmid clones
were used to construct the maps for VII and XV, respectively, forming two unique
contigs that cover the entirety of chromosomes (1091 kb each), except the
telomeric repeats. Colinearity of the cosmid inserts with yeast DNA was verified,
and the physical maps were eventually compared with the independently generated
genetic maps.
PMID- 9639308
TI - An extracellular meiosis-promoting factor in Saccharomyces cerevisiae.
AB - Meiosis and sporulation in the yeast Saccharomyces cerevisiae has been
classically viewed as an example of unicellular, eukaryotic differentiation that
occurs in response to nutritional starvation. We present evidence that S.
cerevisiae produces an extracellular factor(s), called meiosis-promoting factor
(MEP), that is required, in addition to starvation conditions, for efficient
meiosis and sporulation. This factor is secreted and accumulates in a cell
density-dependent fashion such that cells at a low density sporulate poorly under
conditions in which cells at a high density sporulate efficiently. Conditioned
medium from sporulating cells at a high density contains a small anionic molecule
that has cytostatic activity and stimulates sporulation of cells at low density
under a normal starvation condition. These results indicate that MEP-mediated
social communication between cells is required for meiosis and sporulation.
PMID- 9639309
TI - Bicarbonate-mediated social communication stimulates meiosis and sporulation of
Saccharomyces cerevisiae.
AB - Meiosis and sporulation in the yeast Saccharomyces cerevisiae requires social
communication, mediated by an extracellular factor which is secreted from cells
during sporulation and accumulates in a cell density-dependent manner. We show
here genetic and biochemical analyses supporting our conclusion that the
extracellular factor is bicarbonate acting as an alkali to elevate extracellular
pH. Sporulation defects of mdh1 (mitochondrial malate dehydrogenase) mutants and
of wild-type cells at low density were rescued extracellularly by addition of
bicarbonate or other alkaline solutions to raise medium pH. Addition of
bicarbonate (or alkalization of medium) raised steady-state levels of mRNA in
respiration-deficient mdh1 mutants and inhibited proliferation of wild-type cells
at low density. These results indicate that the two conditions (respiration
competency and high cell density), required for meiosis and sporulation, are
essential for extracellular accumulation of bicarbonate and resulting
alkalization of medium.
PMID- 9639310
TI - The Saccharomyces cerevisiae early secretion mutant tip20 is synthetic lethal
with mutants in yeast coatomer and the SNARE proteins Sec22p and Ufe1p.
AB - Tip20p is an 80 kDa cytoplasmic protein bound to the cytoplasmic surface of the
endoplasmic reticulum (ER) by interaction with the type II integral membrane
protein Sec20p. Both proteins are required for vesicular transport between the ER
and Golgi complex. Recently, sec20-1 was found to be defective in retrograde
transport. A collection of temperature-sensitive tip20 mutants are shown to be
lethal in combination with ufe1-1, a target SNARE of the ER and ret2-1, yeast
delta-COP. A subset of tip20 mutants was found to be lethal in combination with
sec20-1, sec21-1, sec22-3 and sec27-1. Since all pairwise combinations of a tip20
mutant, sec20-1, and ufe1-1 are lethal, Tip20p and Sec20p might be part of the
docking complex for Golgi-derived retrograde transport vesicles. Since carboxy
terminal tip20 truncations are lethal in combination with mutants in three
coatomer subunits, Tip20p might be involved in binding or uncoating of COPI
coated retrograde transport vesicles.
PMID- 9639311
TI - Isolation of the Pichia pastoris PYC1 gene encoding pyruvate carboxylase and
identification of a suppressor of the pyc phenotype.
AB - We have cloned and characterized a gene encoding pyruvate carboxylase from the
methylotrophic yeast Pichia pastoris. Disruption of this gene produced inability
to grow in minimal medium with glucose as carbon source and ammonium as nitrogen
source. Growth was possible with aspartate or glutamate as nitrogen source. The
gene PpPYC1 expressed from its own promoter was able to rescue the phenotype of
Saccharomyces cerevisiae mutants devoid of pyruvate carboxylase. In a P. pastoris
strain carrying a disrupted PpPYC1 gene we have isolated spontaneous mutants able
to grow in non-permissive conditions. In a mutant strain grown in glucose several
enzymes sensitive to catabolite repression were derepressed. The strain also had
elevated levels of glutamate dehydrogenase (NAD) both in repressed and
derepressed conditions.
PMID- 9639312
TI - Genomic disruption of six budding yeast genes gives one drastic example of
phenotype strain-dependence.
AB - Using PCR to construct disruption cassettes, null alleles of six genes have been
created in Saccharomyces cerevisiae. In a FY1679 background, no defects were
detected in any of the haploid deletion mutants with respect to growth, gross
morphology, or mating. A diploid FY1679-derived delta ygl194c/delta ygl194c
homozygous disruptant displayed reduced sporulation. In contrast to the lack of
phenotypic consequences of delta yol100w disruptions in the FY1679 background, in
the CEN.PK2 strain even a heterozygous disruption of the same gene caused
striking effects, very slow vegetative growth and highly impaired sporulation.
Tetrad analysis showed YOL100w to be an essential gene in this strain. A copy of
the YGL194c or the YOL100w wild-type gene borne on a centromeric episomal plasmid
was introduced into a corresponding disruption mutant strain, and in both cases
was found to partially complement the defects.
PMID- 9639313
TI - Identification of a putative histidine kinase two-component phosphorelay gene
(CaHK1) in Candida albicans.
AB - We have cloned and analysed the sequence of a putative histidine kinase, two
component gene (CaHK1) from Candida albicans. This gene encodes a 2471 amino acid
protein (Cahk1p) with an estimated molecular mass of 281.8 kDa. A homology search
of Cahk1p with other proteins in the databases showed that Cahk1p exhibits the
greatest homology at its C-terminus with both the sensor and regulator components
of prokaryotic and eukaryotic two-component histidine kinases. A further analysis
of this homology showed that the Cahk1p possessed both sensor and regulator
domains in the same polypeptide. Also, Cahk1p is likely to be a soluble protein.
The sensor kinase domain of Cahk1p contains conserved motifs that are
characteristic of all histidine kinase proteins, including the putative histidine
which is believed to be autophosphorylated during activation, ATP binding motifs
and others (F- and N-motifs), with unknown function. The Cahk1p regulator domain
also contains conserved aspartate and lysine residues and the putative aspartate,
which is secondarily phosphorylated by the autophosphorylated histidine. Finally,
according to the codon usage frequency of the CaHK1 gene in comparison with other
genes from C. albicans, there would appear to be a low level of expression of the
gene.
PMID- 9639314
TI - Isolation and characterization of the Candida albicans SEC4 gene.
AB - The SEC4 gene product is a major component of the protein secretion machinery.
More specifically, it is believed to play a pivotal role in targeting and fusion
of secretory vesicles to the plasma membrane. Its recently described implication
with the Saccharomyces cerevisiae Rho3p, which is required for directing growing
points during bud formation, has prompted us to investigate the role and function
of Sec4p in the morphological changes of the yeast pathogen Candida albicans. We
have therefore cloned the C. albicans SEC4 gene. It encodes a 210 amino acids
long protein sharing up to 75% homology to the S. cerevisiae homolog, when
conserved changes are allowed. Its RNA is constitutively expressed in C. albicans
grown under various physiological conditions. We also show that it can
functionally complement a S. cerevisiae sec4 thermosensitive mutant.
PMID- 9639315
TI - Genetic organization and sequence analysis of the hypha-specific cell wall
protein gene HWP1 of Candida albicans.
AB - A previously isolated partial cDNA encoding a cell wall protein antigen found on
hyphal surfaces of the opportunistic fungal pathogen, Candida albicans (Staab et
al., 1996) was used to clone the complete hyphal wall protein 1 gene (HWP1).
Hyphal forms of C. albicans invade mucosal surfaces of immunocompromised patients
such as those with AIDS. HWP1 consisted of an open reading frame predicting an
acidic protein (pI of 3.37) with a calculated molecular size of 61,122. The
antigenic domain was located in the N-terminal third of the protein. The
remainder of the protein contained abundant hydroxy amino acids, and terminated
with a string of 15 amino acids typical of sequences specifying post
translational modification with glycosylphosphatidylinositol (6PI). The analyses
suggested that Hwp1 is a glucan-linked protein with serine/threonine-rich regions
that are predicted to function in extending a ligand-binding domain into the
extracellular space.
PMID- 9639317
TI - Current awareness on yeast.
PMID- 9639316
TI - The HIS4 gene from the yeast Kluyveromyces lactis.
AB - The Kluyveromyces lactis HIS4 gene was cloned by complementation of a
Saccharomyces cerevisiae his4 mutant. Sequence analysis revealed a 2388 bp open
reading frame encoding a single polypeptide predicted to encompass three distinct
enzymatic activities (phosphoribosyl-AMP cyclohydrolase, phosphoribosyl-ATP
pyrophosphohydrolase and histidinol dehydrogenase). This structural organization
is strikingly similar to that of the His4 proteins from S. cerevisiae and Pichia
pastoris. Transcript analysis detected a single mRNA species of 2.5 kb.
PMID- 9639318
TI - Immunolocalization of tumour necrosis factor-alpha (TNF-alpha) in the placental
bed of normotensive and hypertensive human pregnancies.
AB - To identify tumour necrosis factor (TNF)-alpha immunopositive cells, third
trimester human placental bed biopsies were selected from nine normotensive
control women, 16 severely pre-eclamptic patients and seven patients with pre
existing hypertension with superimposed pre-eclampsia. In addition, five first
and early second trimester specimens were included in the study. Immunostaining
was performed with a mouse IgG1 monoclonal antibody (J1D9) reactive specifically
with human TNF-alpha (1:300 ascitic fluid), using a biotin-streptavidin
peroxidase technique. Variable staining of stromal cells was noted in all
biopsies. Specimens of early pregnancy showed marked immunostaining for TNF-alpha
on proliferating tips of anchoring villi, invasive interstitial cytotrophoblast
(but not the multinuclear giant cells), and endovascular trophoblast invading the
spiral arteries. At term, weak staining was found in trophoblast incorporated
within spiral artery walls. In biopsies from pre-eclamptic patients, spiral
arteries without physiological change showed very little staining except in
atherotic vessels where the infiltrated lipophages often showed intense
immunolabelling. The marked presence of TNF-alpha in extravillous cytotrophoblast
of young specimens is suggestive of a role in early invasion. Immunostaining of
foam cells in non-invaded spiral arteries in pre-eclampsia at or near-term
indicates a potential role of this cytokine in the development of atherotic
lesions.
PMID- 9639319
TI - Decidual spiral artery remodelling begins before cellular interaction with
cytotrophoblasts.
AB - Endometrial arteries undergo structural alterations during pregnancy to increase
blood flow to the intervillous space. It is hypothesized that physiologic change
in decidual arteries is similar to vascular remodelling seen in other organs.
Histologic features of spiral arteries in secretory endometrial biopsies were
compared blindly to decidual arteries from elective abortions. Similar sections
were stained for trophoblastic and vascular antigens. Spiral arteries in
endometrium from ectopic (tubal) and intrauterine pregnancies were compared also.
Evidence of decidual endothelial activation was sought using antibodies to
vascular cell adhesion molecule (VCAM-1). As expected, decidual arteries were
significantly different than arteries in secretory endometrium: there was more
endothelial basophilia, vacuolation, and arterial dilation in early pregnancy.
Some vessels had disorganized or hypertrophied smooth muscle layers. Similar
structural alterations were seen in endometrium of ectopic pregnancies, and in
the decidua parietalis of intrauterine pregnancies. Immunohistochemical studies
confirmed that these alterations occurred in the absence of cellular interaction
with extravillous cytotrophoblasts. Independently of trophoblasts, decidual
endothelial cells expressed VCAM-1. It is concluded that the initial stages of
physiologic change are characterized by vascular remodelling, which occur in the
absence of trophoblast invasion of the spiral arteries. Arterial modifications in
decidua begin as a maternal response to pregnancy.
PMID- 9639320
TI - Gene expression of nitric oxide synthase in cultured human term placental
trophoblast during in vitro differentiation.
AB - The human placental syncytiotrophoblast is derived from differentiating
cytotrophoblasts and is in contact with maternal blood. This endothelial function
positions the trophoblast to regulate maternal-fetal exchange and to influence
circulatory dynamics through paracrine interactions in the placenta. Two isoforms
of nitric oxide synthase (NOS) are expressed in placenta, and northern analysis,
reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry
were used to correlate expression of the type II, inducible NOS (iNOS) and the
type III, endothelial NOS (eNOS) with state of differentiation in cultured
trophoblast from term placentae. It was also tested whether cytokines known to
induce NOS in other cell systems would induce iNOS in human trophoblast. The mRNA
for eNOS was detected by RT-PCR, but not by Northern analysis, in cultures grown
for 24 h when cytotrophoblasts were dominant. In contrast, eNOS mRNA was abundant
in cultures grown for 72 h when syncytiotrophoblast was present.
Immunocytochemical staining for eNOS protein showed specific fluorescence in a
few cells in cultures at 24 h, but the vast majority of cells expressed eNOS at
72 h. The iNOS isoform was expressed neither basally in any trophoblast culture
nor was this isoform induced in cultures exposed to interleukin-1, tumour
necrosis factor-alpha, interferon-gamma and lipopolysaccharide. The in vitro
pattern of trophoblast eNOS expression models the in vivo pattern of eNOS
expression described for villous trophoblast. The results suggest that eNOS plays
a role in human trophoblast differentiation and function.
PMID- 9639321
TI - Increase in expression and activity of thrombomodulin in term human
syncytiotrophoblast microvilli.
AB - A comparative study of thrombomodulin (TM), a potent natural anticoagulant, was
performed in first trimester and term human placentae. Immunoreactive TM was
observed on fetal vascular endothelium and syncytiotrophoblast at both
gestational ages. Staining was stronger in term than in early placentae,
particularly along the microvillous apical membrane of the syncytiotrophoblast.
Similarly, a higher level of TM mRNA was detected by RT-PCR (P<0.02) and Northern
blot analysis in extracts of whole term placentae. The localization of TM on
syncytial microvilli was confirmed by electron microscopy after immunogold
labelling. When isolated microvilli were compared at both gestational ages; a
significant 2.3-fold increase in TM protein was observed in term microvilli as
compared to first trimester microvilli by Western blot analysis (P<0.005) and
ELISA (P<0.05). This higher level of TM in term microvilli was associated with an
increase in its ability to activate protein C, from 3.7 +/- 1.2 to 8.7 +/- 4.2
mOD/min/microg protein +/- s.d. (P<0.01) in first trimester and term microvilli,
respectively. The modulation of biologically active TM at the syncytial membrane
exposed to maternal blood according to the length of gestation suggests that TM
may be involved both in maternal haemostasis within the intervillous spaces, and
also in the trophoblast differentiation process.
PMID- 9639322
TI - Demonstration of the expression of CD95 ligand transcript and protein in human
placenta.
AB - Tolerance of the fetal allograft enables the human conceptus to implant itself
into the maternal uterus and survive and grow there. This tolerance phenomenon
remains largely obscure, notably because it appears to be controlled by multiple
mechanisms. CD95 ligand (CD95-L), which can trigger death of CD95-positive cells
by apoptosis, may participate in inducing anti-fetus-sensitized CD95-positive T
lymphocytes to enter apoptosis. Using immunohistochemistry (first trimester and
term placentae), FACS assays (term placenta) and RT-PCR assays (term placenta),
the presence of CD95-L protein and mRNA has been shown in crude placental tissue
preparations and isolated placental cells. Among the latter, CD95-L expression
was detected in trophoblastic cells, fetal blood cells (mRNA only) and also the
Hofbauer macrophages. No CD95-L was detected in fibroblasts or fetal endothelial
cells. Thus trophoblastic cells, Hofbauer macrophages, and perhaps also fetal
blood cells could form a sequential barrier blocking maternal activated defence
cells bearing CD95 molecules.
PMID- 9639323
TI - Cellular specificity of fibroblastic proMMP-3 downregulation by normal or cancer
trophoblastic cells.
AB - It has been shown previously that endometrial fibroblast prometalloproteinase-3
(proMMP-3) secretion is inhibited by normal cytotrophoblasts as a result of
paracrine interactions. To investigate the specificity of this downregulation,
two different types of co-culture were used. First, peritoneal and synovial
fibroblasts obtained from human tissue biopsies were co-cultured with normal
cytotrophoblasts. By contrast to what has been observed with endometrial
fibroblasts, their proMMP-3 secretion increased though their morphology was
slightly modified. Secondly, the regulation of endometrial proMMP-3 secretion was
tested in co-cultures with two choriocarcinoma cell lines (JAr and JEG-3 cell
lines). With tumoral cytotrophoblastic cells, endometrial fibroblasts became
decidua-like cells and JAr and JEG-3 cell lines grew in syncytium. However, co
culture of endometrial fibroblasts with JAr and JEG-3 choriocarcinoma cells did
not decrease proMMP-3 secretion. The present results show that endometrial proMMP
3 downregulation is tissue specific and does not depend on cell differentiation.
A cytotrophoblast cell membrane factor which might not be expressed in tumoral
cells could probably play a role in paracrine relations between epithelial cells
and surrounding stroma.
PMID- 9639324
TI - Suppression by beta-mercaptoethanol of the intracellular hormonal dynamics of
human chorionic gonadotropin-beta subunit (hCG-beta) in BeWo choriocarcinoma
cells.
AB - The effects of beta-mercaptoethanol (ME) on the steady-state level of mRNA of the
human chorionic gonadotropin-beta subunit (hCG-beta) and the intracellular
hormonal dynamics of the product protein were examined in BeWo cells, a
choriocarcinoma cell line, using Northern blot analysis and a radioimmunoassay
(RIA) specific for hCG-beta. ME reduced both medium and intracellular contents of
hCG-beta in a dose-dependent manner, with its minimum effective dose being 0.01
per cent. The highest dose used (0.1 per cent) caused more than 90 per cent
inhibition with both parameters, without affecting the cell number and the cell
viability as verified by trypan blue exclusion. Significant reductions in both
the medium and intracellular contents began to occur 6 h after the onset of
incubation with ME. The ME-induced suppressions were reversible. Northern blot
analysis showed that ME had no effects on the steady-state level of hCG-beta
mRNA. When medium and cell lysates collected from ME-free incubations were
incubated with 0.03 per cent ME, there were significant reductions of
immunoreactive hCG-beta with both the medium and cell lysates. The magnitude of
reduction, however, was much greater with the latter (75 per cent) than with the
former (25 per cent). In contrast, the hCG-beta immunoreactivity of the RIA
reference preparation was unaffected by incubation with ME. These results
suggested that the major target(s) of ME action were the intracellularly located
hCG-beta molecule, presumably its intramolecular disulphide bonds. It must also
be pointed out that the hCG-beta molecule synthesized and secreted by BeWo cells
have some structural deviation from the reference standard molecule of normal
trophoblastic origin to explain the differential susceptibility to ME.
PMID- 9639325
TI - Decreased placental and umbilical cord glycogen levels associated with meconium
stained amniotic fluid.
AB - Most frequently, placental glycogen has been studied as an index of fetal
nutrition. There are no published studies of placental glycogen as an index of
fetal stress. In this study of 1573 samples from 71 placentae, glycogen levels in
the placental disk, fetal membranes and umbilical cord of normal uncomplicated
pregnancies were compared with those in complicated pregnancies. The complicated
pregnancies included preterm delivery, hypertensive disorders, inadequate
prenatal care, substance abuse, maternal fever or infection, obesity, diabetes
mellitus, premature rupture of membranes, intrauterine growth retardation, sickle
cell trait, and acute meconium staining of amniotic fluid at delivery. The data
showed that the only significant differences were in the subgroup complicated by
meconium-stained amniotic fluid in which the placental disks and umbilical cords
had significantly lower (P=0.0006) glycogen levels. This finding suggests a
relatively specific association. It is interesting to speculate that the passage
of meconium with its vasoconstrictive effect increases utilization of local
glycogen stores, decreases local glycogen reserves needed for the work of further
vasoconstriction, and, in the event of subsequent acute stress, impairs vascular
perfusion of tissues. In this way, meconium could predispose the infant to
asphyxia.
PMID- 9639326
TI - Stimulation of prostaglandin production from intact human fetal membranes by
bacteria and bacterial products.
AB - The addition of live or sonicated Escherichia coli, or endotoxin from E. coli
increased the release of prostaglandins (PG) on both sides of intact human fetal
membranes after 24 h of incubation, indicating that live bacteria were not
required to activate prostaglandin production. Time-course studies showed that
the levels of PGE2 and PGF2alpha on the fetal side of the membrane were increased
6 h after the addition of endotoxin, whereas levels on the maternal side
increased within 1-2 h. These changes were independent of the side to which the
endotoxin was added, indicating that a stimulatory factor passes through the
fetal membranes. This factor is not endotoxin, which did not cross the membranes,
and further studies are required to identify this endogenous stimulus.
Prostaglandin metabolite levels were either unaffected or increased by endotoxin,
indicating that the main effect is at the level of increased prostaglandin
biosynthesis rather than decreased metabolism.
PMID- 9639327
TI - Culture of human amniotic cells: a system to study interferon production.
AB - This study investigated whether primary culture of human amniotic membrane cells
(PCHAM) could be used as an in vitro model system for the study of interferon
(IFN) production. PCHAM cells infected with Newcastle disease virus (NDV)
produced the two antigenic types of IFN, previously shown in a amniotic membrane
cells (HAM) system. PCHAM IFN was detected as early as 2 h after NDV infection
and was composed by two antigenically distinct fractions, one neutralized with
anti-HuIFN beta antibody and another that is not related to IFN beta, -alpha and
gamma. These fractions correspond respectively to 80 and 20 per cent of the IFN
produced 4 h after virus induction, 55 and 45 per cent of the IFN produced from 4
to 12 h and 67 and 33 per cent of the IFN produced 12 h after virus induction. A
cDNA library, established from PCHAM with or without NDV infection, was screened
for IFN alpha and -beta using specific primers. The PCR product, amplified by IFN
beta primers, was cloned, sequenced and expressed in Escherichia coli M15. The
sequences of several cloned cDNAs were identical to HuIFN beta gene and the
antiviral activity of the expressed protein was neutralized only by antiHuIFN
beta antibody. The other IFN fraction not neutralized by polyclonal antibodies
anti-IFN beta, -alpha and -gamma is now being studied.
PMID- 9639328
TI - Mechanisms of chloride transport across the syncytiotrophoblast basal membrane in
the human placenta.
AB - Chloride transport mechanisms in isolated plasma membrane vesicles were studied
to characterize pathways for transcellular transport of chloride. Microvillous
membrane (MVM) and basal membranes (BM) vesicles were isolated from term
placentae. Western blot analysis of the anion exchanger isoform 1 (AE1)
demonstrated that the density of AE1 was 12-fold higher on the MVM compared to
the BM. At 30 sec, the Cl- uptake in the absence of a potential difference (p.d.)
was 457.3 +/- 69.7 and 111.0 +/- 29.1 pmol/mg protein in MVM and BM, respectively
(mean +/- SEM, n=6). Chloride transport pathways were characterized using
diisothiocyano-2'2-disulphonic stilbene. (DIDS, 0.1 mM) and diphenylamine-2
carboxylate (DPC, 0.5 mM) in the absence or presence of inside positive membrane
potentials. Anion exchange (DIDS-sensitive uptake at zero mV) was found in the
MVM only. Both MVM and BM showed increased chloride uptake in the presence of
inside positive potentials, suggesting the presence of chloride conductance
pathways. The chloride uptake with a 25-mV inside positive p.d. could be
inhibited by both DIDS and DPC in MVM and BM. However greater potentials (50 mV)
showed no significant inhibition by DIDS or DPC in BM. In conclusion, the anion
exchanger is unlikely to contribute significantly to chloride fluxes across BM.
The data also suggest the presence of Cl- conductance pathways in both the MVM
and BM which are sensitive to both DIDS and DPC.
PMID- 9639330
TI - Glycine is not formed through the amino transferase reaction in human or rat
placenta.
AB - The fetus has a substantial demand for glycine, which is satisfied in part by
placental formation. The ability to form glycine through the activity of
alanine:glyoxylate aminotransferase enzyme was measured in placentae from normal
term human pregnancies and placentae from rats at day 20 of gestation. There was
no detectable enzyme activity in either human or rat placentae, although activity
was measured in rat liver. It is concluded that in the placenta glycine is only
formed from serine through the activity of serine hydroxymethyl transferase
enzyme, which uses folate as a cofactor, because there are no other known
metabolic pathways for endogenous glycine production.
PMID- 9639329
TI - Sodium-independent lysine uptake by the BeWo choriocarcinoma cell line.
AB - Transport of L-lysine by a cultured placental trophoblast cell line was
investigated by characterization of L-[3H]lysine uptake. In the mononuclear form
of the BeWo clone b30 choriocarcinoma cell, at least two sodium-independent
systems are present. Concentration dependence data were fitted by a two system
model with Km values (+/- s.e.) of 2 +/- 0.7 and 94 +/- 31 microM and Vmax values
(+/- s.e.) of 0.7 +/- 0.3 and 25 +/- 6.0 nM/mg DNA/min. A portion of sodium
independent uptake was inhibited by the sulphydryl modifying reagent N
ethylmaleimide (NEM). Following NEM treatment, the data were fitted by a single
system with Km = 10 +/- 2 microM AND Vmax = 5.1 +/- 0.8 nM/mg DNA/min. In the
absence of sodium, NEM-resistant uptake was sensitively inhibited by leucine
whereas NEM-sensitive uptake was not inhibited by leucine. It is concluded that
like placental basal membrane, the mononuclear BeWo cell possesses two sodium
independent L-lysine transport systems. The high-capacity, NEM-sensitive, leucine
insensitive system resembles the widespread system y+. The high-affinity, NEM
resistant, leucine-sensitive system resembles system b(0,+).
PMID- 9639331
TI - Single case report: late gestational fetal sheep may survive blockage of the
ductus venosus for 1 week.
PMID- 9639332
TI - Microelectrode measurements of the potential profile of the pig placenta in
vitro: evidence for an electrically positive compartment.
PMID- 9639333
TI - Competition in the NHS internal market: an overview of its effects on hospital
prices and costs.
AB - The 1989 reforms of the UK National Health Service (NHS) introduced competition
in the supply of hospital services. This paper synthesizes both the theory
underlying the introduction of competition into the NHS, and the limited existing
evidence on whether competition affects the prices posted by sellers of medical
services, and the costs of producing these services. The results indicate high
levels of price variability, widespread disregard for average cost pricing rules
and some indication that competition had some effect on prices. It appears that
lower prices may be offered to smaller purchasers, such as General Practice Fund
Holders (GPFH). This effect of competition on price was mirrored, with a delay,
in hospital costs.
PMID- 9639334
TI - Volume responses to Medicare payment reductions with multiple payers: a test of
the McGuire-Pauly model.
AB - The effects of changing financial incentives on physician's practice behaviour
have long been of interest to researchers and policy makers. We test a model of
physician volume response within the context of multiple payers developed by
Thomas McGuire and Mark Pauly. A panel data set covering discharges from about
200 hospitals in the US over 45 months is used to carry out the empirical
investigation. A fixed-effect model with generalized least squares and
instrumental variable specifications is used to compute empirical evidence of
volume responses from eight specialties experiencing varying degrees of Medicare
payment reductions following the implementation of Omnibus Budget Reconciliation
Acts of 1989 and 1990. The empirical findings are compared with McGuire and
Pauly's simulated predictions. We note that in examining physician responses to
Medicare payment reductions in the context of a multi-payer environment, it
becomes evident that only fixing one payer's reimbursement policy is at best a
partial solution to cost containment. We echo observations made by other analysts
that physician responses to payment changes can be quite complex. Physicians do
not all respond to payment reduction in the same way.
PMID- 9639335
TI - Use of economic evaluation guidelines: 2 years' experience in Canada.
AB - Considerable effort has been expended in recent years in the development of
methodology guidelines for economic evaluation of pharmaceutical products, driven
in part by the desire to improve the rigour and quality of economic evaluations
and to help decision making. Canada was one of the first countries to develop
such guidelines and to encourage their use. This paper examines the extent to
which the economic evaluations that were submitted to the Canadian Coordinating
Office for Health Technology Assessment in the last two years adhered to Canadian
guidelines. The analytic technique employed by twelve studies as well as the
comparator used, the perspective taken, the outcome measure selected, the cost
items that were taken into consideration and the extent of sensitivity analyses
that were performed are reviewed in this paper. It can be concluded that although
studies have been of variable quality, the majority of them were well presented,
complete and transparent, due in part to the guidelines. Except for the
perspective of the analysis, guidelines were, in many respects, adhered to and
did not restrict investigators to specific methodologies or specific techniques.
They were also instrumental in ensuring a minimum set of standards.
PMID- 9639336
TI - Drug use, drug abuse, and labour market outcomes.
AB - This paper examines the relationship between illicit drug use and labour market
success, and in doing so addresses two shortcomings of the previous literature.
First, unlike many previous analyses, ours accounts for differences in intensity
of use using clinically based diagnostic measures. Second, while recent studies
focus only on young adults, we analyze a prime-age (30-45-year-olds) sample as
well. Our results indicate that these differences are important. Similar to
previous studies, we find evidence of a positive relationship between drug use
and income for young workers. However, we also find some evidence of lower
incomes for young workers reporting daily use of illicit drugs. For prime-age
men, we find strong evidence that problematic drug use (as indicated by either a
diagnosis of pathological use or dependence or by daily use) is negatively
related to income. We also find a negative relationship between problematic use
and employment among prime-age, but not younger, men.
PMID- 9639337
TI - Effects of selective contracting on hospital efficiency, costs and accessibility.
AB - This paper exploits a natural experiment in the state of California, to show that
pro-competitive healthcare policy may have unintended long-term liabilities
unless the system as a whole is carefully designed to preserve access to care for
the poor. California's Medicaid Reform Act of 1982 increased competition among
hospitals in urban areas, with legislation which allowed direction of patients to
more efficient providers via selective contracting. This slowed the average rate
of hospital cost inflation, and saved the state billions of dollars. The
substantial short-term savings have been documented in empirical research, but
little attention has been paid to the longer-term effects of the reforms. We find
that Medicaid contracts were awarded to more efficient hospitals. The
distributional effects post-reform resulted in efficiency gains for most
hospitals, but costs escalated for over half of the public hospitals in the
sample, as their uncompensated care burdens rose. Public hospitals continued to
fail during the period, leaving over half of California's counties without a
county hospital by 1990. Because public hospitals provide the vast majority of
healthcare for the poor in California, there is reason for concern about erosion
of their access to care as an unintended outcome of pro-competitive reforms.
PMID- 9639338
TI - Technical efficiency in the clinical management of critically ill patients.
AB - The purpose of this paper is to obtain empirical measures of performance in the
management of critical patients treated in intensive care units (ICUs) and to
evaluate the factors associated with performance, in a two stage approach. In the
first stage, this paper uses an extended version of Data Envelopment Analysis
(non-discretionary and categorical variables, and weight constraints under
consideration) to obtain measures of technical efficiency in the treatment of 993
critical care patients in intensive care units in Catalonia (Spain) in 1991-92.
The model incorporates accurate individual measures of illness severity from
Mortality Probability Models (MPM II0) and quality outcome measures in the input
output set to obtain non-biased efficiency measures. In the second stage, a
loglinear regression model is applied to test a number of hypothesis about the
role of different environmental factors--such as ownership, market structure,
dimension, internal organization, diagnostic, mortality risk, etc.--to explain
differences in the efficiency scores.
PMID- 9639339
TI - Comparison of extrinsic and intrinsic neuromodulation in two central pattern
generator circuits in invertebrates.
AB - There are many sources of modulatory input to CPGs and other types of neuronal
circuits. These inputs can change the properties of cells and synapses and
dramatically alter the production of motor patterns. Sometimes this enables the
production of motor patterns by the circuit. At other times, the modulation
allows alternate motor patterns to be produced by a single circuit. Modulatory
neurones have fast as well as slow actions. In some cases, such as with GPR, the
two types of effects are due to the release of co-transmitters. In other cases,
such as with the DSIs, a single substance can act at different receptors to cause
fast and slow postsynaptic actions. The effect of a neuromodulatory neurone is
determined by the type of receptor on the target neurone. Thus a single
modulatory neurone evokes a suite of actions in a circuit and thereby produces a
co-ordinated output. Extrinsic and intrinsic sources of neuromodulation have
different sets of constraints acting upon them. For example, extrinsic
neuromodulation can easily be used for motor pattern selection; a different
pattern is produced depending upon which modulatory inputs are active. However,
intrinsic neuromodulation is not well suited to that task. Instead, it is useful
for self-organizing properties and experience-dependent effects. One clear
conclusion from this work and other work in the field is that neuromodulation by
neurones intrinsic and extrinsic to CPGs is not uncommon (Katz, 1995; Katz &
Frost, 1996). It is part of the normal process of motor pattern generation. As
such, it needs to be considered when discussing mechanisms for neuronal circuit
actions.
PMID- 9639340
TI - A method for reversible permeabilization of isolated rat ventricular myocytes.
AB - A method is described that enables the cell membrane of isolated rat ventricular
myocytes to be permeabilized and resealed while maintaining cell viability.
Streptolysin O, a cholesterol-binding cytolysin, was used to form pores in the
surface membrane; subsequent incubation with 5% fetal bovine serum was used to
reverse this permeabilization. The efficacy of membrane permeabilization and
resealing was ascertained using a simultaneous double-staining technique using
propidium iodide, a marker for cells with permeabilized membranes, and
fluorescein diacetate, a marker for viable cells. This procedure allowed a
distinction to be made between dead cells, unpermeabilized cells and viable cells
that had been successfully permeabilized and resealed. The accessibility of the
cell interior during permeabilization was investigated by including fluorescein
isothiocyanate (FITC)-labelled dextrans (11, 38 and 148 kDa) and bovine serum
albumin (67 kDa) in the permeabilization buffer, and localizing the FITC label
using confocal microscopy following resealing. The confocal images showed that
these molecules entered the cells and were retained after resealing. Following
the permeabilization-resealing protocol, cells appeared to have both normal
morphology and response to electrical stimulation. Thus this appears to be a
cheap, simple and effective method to introduce relatively large molecules into
cardiac myocytes.
PMID- 9639341
TI - Rapid modulation of L-type calcium current by acutely applied oestrogens in
isolated cardiac myocytes from human, guinea-pig and rat.
AB - Gender-based differences in cardiovascular mortality may be due to a cardio
protective effect of oestrogens on the myocardium. However, mRNA expression of
oestrogen receptors in myocardial tissue of the adult heart has yet to be
demonstrated. Furthermore, a calcium antagonistic action of 17beta-oestradiol on
myocardial tissue has been discussed. Therefore, two subjects were investigated
in atrial myocytes of the human, and ventricular myocytes of guinea-pig and rat
in this study. (1) Are oestrogen receptors expressed in adult myocardial cells?
(2) Is there an influence of oestrogens on the L-type calcium current of cardiac
myocytes? Expression of oestrogen receptors was investigated by reverse
polymerase chain reaction. L-type calcium current was usually measured by the
patch-clamp technique in whole-cell recording mode under selective recording
conditions, i.e. overlapping currents were blocked. One series of experiments was
performed in perforated patch configuration to avoid internal perfusion. 17beta
oestradiol inhibited L-type calcium current reversibly in all three species. At
10(-5) M, the inhibition was 15-20%. This inhibition was independent of the sex
and the species. A full concentration response curve of 17beta-oestradiol on
basal L-type current was recorded from female guinea-pig myocytes. The inhibition
increased from 2% at 10(-7) M to about 30% at 10(-4) M 17beta-oestradiol. The
values could be fitted by a sum of two sigmoidal functions with log EC50 values
of -6.5 and -4.9 M and Hill slopes of 2.5 for both. The specificity of the 17beta
oestradiol action was tested by recording the L-type current in the presence of
17alpha-oestradiol and oestrone. 17alpha-oestradiol also inhibited the current,
but with a maximal inhibition of only 17%. The concentration-response curve could
be fitted by a single sigmoidal function (log EC50 -6-3 M; Hill slope 0.55).
Oestrone did not influence the current at all. The decrease in L-type current
after the application of 17beta-oestradiol via a rapid perfusion system developed
with a time constant of 3-4 s, which was in the same range as that for the
influence of isoprenaline. The isoprenaline-stimulated L-type current was much
more susceptible to the inhibition by 17beta-oestradiol, i.e. in pre-stimulated
cells (1) the inhibitory effect is significantly higher (e.g. at 10(-5) M,
inhibition was 36.3% compared with 11.2% in untreated cells) and (2) an
inhibitory effect can be seen with oestradiol concentrations as low as 10(-9) M.
Although the concentrations needed to gain a calcium antagonistic influence on
the basal current were much too high to explain a cardio-protective influence of
oestrogens, the presence of oestrogen receptors in cardiac myocytes of all three
species, together with the shift in concentration dependence following pre
stimulation by isoprenaline, suggest that myocytes are a potential target for
oestrogen.
PMID- 9639342
TI - Calcium-inhibitable current in cultured embryonic chick cardiac myocytes:
possibly via a novel chloride channel.
AB - The role of extracellular Ca2+ (Ca(2+)o) in the modulation of cardiac Cl-
currents (I(Cl)) such as those activated by cAMP or swelling is uncertain. The
effects of Ca(2+)o and extracellular cadmium (Cd(2+)o) on Cl- currents in
cultured chick cardiac myocytes were investigated in Na+- and K+-free internal
and external solutions using the whole-cell patch-clamp technique. In the absence
of Na+ and K+ internally and externally, the whole-cell current was predominantly
I(Cl). In the absence of cAMP, removal of Ca(2+)o (+ 1 mM EGTA) resulted in an
increase in the current that was suppressed by reduction of Cl(o)- with a
rightward shift of the zero-current potential towards the CI- reversal potential.
We designated this current as a Ca2+-inhibitable I(Cl). Addition of 0.5 mM
Cd(2+)o with or without removal of Ca(2+)o also resulted in a 1.5- to 2.0-fold
increase in I(Cl) that was attenuated by 1 mM DIDS (4,4'-diisothiocyanatostilbene
2,2'-disulphonic acid). Under similar conditions, I(Cl) activated by Cd(2+)o (in
1 mM Ca(2+)o solution) was not further increased by subsequent removal of
Ca(2+)o, suggesting that addition of Cd(2+)o and removal of Ca(2+)o activated the
same I(Cl). In contrast, exposure to 1 microM forskolin further enhanced I(Cl) in
the presence of Cd(2+)o. With 10 microM cAMP in the pipette solution, Ca2+
inhibitable I(Cl) could be activated in myocytes that do not possess cAMP
activated Cl- channels, indicating that activation of Ca2+-inhibitable I(Cl) does
not require cAMP. In the presence of cAMP, in cells that display the cAMP
activated I(Cl), removal of Ca(2+)o resulted in a further increase in I(Cl)
comparable to the Ca2+-inhibitable I(Cl). The Ca2+-inhibitable I(Cl) was
minimized when pipette solutions contained 1.5 microM Ca2+. These results suggest
that removal of Ca(2+)o or application of Cd(2+)o activates a Ca2+-inhibitable
I(Cl) that is distinct from the cAMP-activated I(Cl).
PMID- 9639343
TI - Differential effects of hypoxia on the intracellular Ca2+ concentration of
myocytes isolated from different regions of the rat pulmonary arterial tree.
AB - Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen
sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been
proposed that hypoxia inhibits a K+ conductance, which promotes membrane
depolarization, subsequent activation of L-type Ca2+ channels and ultimately
constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+
concentration ([Ca2+]i) of single myocytes isolated from the rat pulmonary
arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1
fluorescence. The basal level of [Ca2+]i was in the range 35-80 nM and cells were
quiescent at rest exhibiting no spontaneous oscillations in [Ca2+]i. When the
extracellular K+ concentration ([K+]o) was raised to 20 mM, the [Ca2+]i increased
from approximately 60 to approximately 100 nM. This increase was abolished by
nifedipine, demonstrating the presence, and need for activation, of functional
voltage-gated L-type Ca2+ channels. Hypoxia (PO2 < or = 30 mmHg; throughout) had
little effect on the resting [Ca2+]i in myocytes isolated from either the main
intrapulmonary artery, or its primary, secondary or tertiary branches. However,
upon raising the [Ca2+]i by increasing [K+]o to 20 mM, hypoxia was found to lower
[Ca2+]i from approximately 110 to approximately 70 nM, in cells isolated from the
main conduit and primary branches of the intrapulmonary artery. In marked
contrast, when [Ca2+]i was raised, by increasing [K+]o to 20 mM, in myocytes
isolated from secondary and tertiary branches of the intrapulmonary artery,
hypoxia induced a further reversible increase in the [Ca2+]i from approximately
160 to approximately 240 nM. Neither hypoxia alone nor in combination with 20 mM
K(+)o induced any increase in the [Ca2+]i in the presence of nifedipine. We
conclude that hypoxia may modulate [Ca2+]i in rat pulmonary artery myocytes only
following its elevation by a depolarizing stimulus.
PMID- 9639344
TI - Changes in contraction, cytosolic Ca2+ and pH during metabolic inhibition and
upon restoration of mitochondrial respiration in rat ventricular myocytes.
AB - Exposure of cardiac muscle to metabolic poisons reduces the availability of
cellular ATP and cardiac dysfunction ensues. In this study rat ventricular
myocytes were exposed to 2-deoxyglucose, iodoacetate and cyanide to induce
complete metabolic blockade. Changes in contraction, cytosolic Ca2+ and pH were
determined during metabolic blockade and following restoration of mitochondrial
ATP production. Metabolic blockade resulted in a rapid failure of contractions
and Ca2+ transients, a rise of diastolic Ca2+, a cytosolic acidosis and
ultimately a rigor contracture. Washing out cyanide during the development of the
rigor contracture led to a rapid relaxation of the contracture, a fall in
cytosolic Ca2+ and a rapid, partial reversal of the cytosolic acidosis. The
partial reversal of the cytosolic acidosis and fall of cytosolic Ca2+ were
abolished in the presence of oligomycin. This suggests that the rapid partial
recovery of cytosolic acidosis could result from the rephosphorylation of ADP to
ATP by the mitochondrial F1,F0-ATPase (a reaction that consumes protons).
PMID- 9639345
TI - Site of catecholamine modulation of feto-maternal electric potential difference
in the pig.
AB - Feto-maternal vascular (PD(F-M)) and amniotic maternal (PD(A-M)) potential
differences were measured simultaneously on seven occasions in six conscious pigs
of 100-106 days gestation. Resting values of PD(F-M) and PD(A-M) were not
significantly different although the range was wide. Fetal intravascular
injection of 20 microg adrenaline, but not of saline, was associated with a
prompt reversible change, of equal magnitude, in both PD(F-M) and PD(A-M). In
some experiments polarity was reversed. Feto-amniotic potential difference did
not change. There was no change in fetal plasma K+ and Na+ concentrations.
Because of the simultaneous and equal alterations in PD(F-M) and PD(A-M)
following adrenaline and the anatomical configuration of the pig conceptus, we
conclude that the catecholamine modifiable component of PD(F-M) is generated by
electrogenesis in the pig placenta, probably by its chorionic (trophoblastic)
cell layer.
PMID- 9639346
TI - Temperature dependence of mechanical power output in mammalian (rat) skeletal
muscle.
AB - Force-velocity data at different temperatures (range, 10-35 degrees C) from
intact fibre bundles are analysed to determine the temperature dependence of the
maximal mechanical power output of fast and slow rat muscles. At 35 degrees C,
the maximal mechanical power was approximately 250 kW m(-3) (=250 microW mm(-3))
in fast (probably an underestimate) and approximately 100 kW m(-3) in slow
muscle. Within the more physiological temperature range (25-35 degrees C), the
temperature coefficient (Q10) of maximum power was 2-2.5. In both muscles, the
maximal power at 10 degrees C was only about 3-5% of that at 35 degrees C, the
decrease being particularly pronounced at temperatures below 20 degrees C (Q10 of
5-7).
PMID- 9639347
TI - Cyclical passive stretch influences the mechanical properties of the inactive cat
soleus.
AB - The effects of cyclical, passive manipulation (PM, 30 min day(-1), 5 days week(
1) for 6 months) mimicking the length excursions observed during stepping on the
mechanical and associated biochemical properties of the inactive cat soleus
muscle were determined in five cats. Inactivity was produced via spinal cord
isolation (SI), i.e. complete spinal cord transections at low thoracic and high
sacral levels and bilateral dorsal rhizotomy between the transection sites.
Passive manipulation was administered to one leg of each SI cat. Compared with
normal controls, SI resulted in approximately 70% decrease in weight, an 80%
decrease in maximum tetanic tension (Po) and an approximately 100% increase in
maximum rate of shortening (Vmax) and myosin adenosine triphosphatase (mATPase)
activity of the soleus. The passive manipulation regime partially ameliorated
these effects. When compared with the control SI soleus, the SI-PM soleus weight
and maximum tetanic tension were 12 and 21% higher, respectively, and the Vmax
and mATPase activity 21 and 12% (p > 0.05) lower, respectively. Thus, inactivity
resulted in a smaller and faster muscle, whereas passive manipulation for only 30
min a day tended to maintain these properties closer to normal control values.
The results suggest a potential therapeutic effect of short bouts of cyclical,
passive manipulation on otherwise inactive skeletal muscles.
PMID- 9639348
TI - Electrocholecystogram: a study of the electromechanical activity of the gall
bladder in a canine model.
AB - To characterize an 'electrocholecystogram' (EChG) for the normal gall bladder
(GB) that might act as a standard for the evaluation of pathological
electrocholecystograms of the diseased GB, ten mongrel dogs (14.4+/-3.2 kg) were
studied. Under anaesthesia, the abdomen was opened and three silver-silver
chloride electrodes were sutured to the GB serosa. The GB pressure was measured
by a perfused catheter introduced through the fundus. The response of the
myoelectrical activity of the GB to balloon distension was tested and the
direction of electrical waves was defined by GB myotomies. Pacesetter potentials
(PPs) were recorded exhibiting the same frequency, amplitude and velocity of
conduction from the three electrodes of each dog on all test days. Action
potentials (APs) followed the PPs randomly and were associated with a rise of the
GB pressure. Balloon distension of the GB caused increased PP and AP frequency.
The electrical waves showed proximally but not distally to GB myotomy, indicating
that they propagate proximo-distally towards the cystic duct. To conclude, the GB
possesses electrical waves which are probably initiated from a 'pacemaker' at the
GB fundus. A normal EChG could be characterized in the canine model. It is
suggested that this EChG might show changes in gall bladder diseases and might
thus act as an investigative tool, provided it can be developed to be performed
percutaneously.
PMID- 9639349
TI - Gas handling in the caecum of the horse.
AB - Electromanometric recordings of caecal pressures were made in chronically
cannulated ponies. Endoscopy allowed direct observation of the caecal base and
cupola while recording intracaecal pressures and enabled a functional
interpretation of caecal pressure profiles. Using gas-tight seals, the caecal gas
cap baseline pressure (tone) was usually below atmosphere, becoming less negative
postprandially. Diurnal variations were observed in the amplitude and frequency
of caecal pressure profiles and the direction of caecal movements, during which
intra-caecal gas cap pressures briefly became positive. A paraprandial (psychic)
phase of enhanced caecal motility was observed. Manipulation of the caecal gas
cap volume, by insufflation of nitrogen gas, demonstrated the capacity of the
caecal base to regulate gas pressures and to eliminate fermenting gases.
PMID- 9639350
TI - Daily patterns of secretion of neurohypophysial hormones in man: effect of age.
AB - The neurohypophysial hormone vasopressin contributes to control of urine output
and, while urine flow shows a clear daily rhythm, there has been debate as to
whether this is true of neurohypophysial hormones. A study was performed on
fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood
samples being taken at regular intervals for the determination of
neurohypophysial hormones and indices of fluid balance. Samples were taken via an
indwelling cannula so that sleep was undisturbed. A daily variation in the plasma
concentrations of oxytocin and vasopressin was demonstrated with concentrations
reaching a nadir in the late afternoon. Concentrations of both hormones peaked at
02.00 h. Vasopressin concentrations were inversely correlated with packed cell
volume, indicating that the altered hormone release was affecting fluid
retention. Consistent with this was the observation that the relationship of
plasma osmolality to vasopressin depended on the time of day. To determine the
effect of ageing, a similar study was performed on nine healthy elderly subjects
with a mean age of 70 years. The nocturnal peak of vasopressin was markedly
attenuated, while oxytocin release was similar to that in the younger group.
These observations confirm the existence of a daily rhythm in the plasma
concentrations of neurohypophysial hormones and indicate that the amplitude of
the vasopressin change decreases with age.
PMID- 9639351
TI - The effects of substrate and fluid provision on thermoregulatory,
cardiorespiratory and metabolic responses to prolonged exercise in a cold
environment in man.
AB - During prolonged exercise in a cold environment, fatigue is generally associated
with a depletion of endogenous glycogen stores. This has lead many authors to
hypothesize that the carbohydrate (CHO) content of fluids ingested in cool
environments should be high, yet this hypothesis has not been specifically
examined. In the present study, six healthy males cycled to exhaustion at
approximately 80% of their maximum oxygen consumption (V2O,max) with either no
drink (ND), a 15% CHO-electrolyte drink (15% CHO) or a 2% CHO electrolyte drink
(2% CHO). Dietary intake and exercise were replicated 2 days prior to each trial.
Mean (S.D.) ambient temperature was 10.0 (0.3) degrees C with a relative humidity
of 72 (2) % and an air velocity of approximately 0.7 m s(-1) on all trials.
Weighted mean skin temperature was calculated, and rectal temperature and heart
rate were recorded at rest, during exercise and at exhaustion. Venous samples
were drawn before and during exercise and at exhaustion for determination of
haemoglobin, haematocrit, blood metabolites and serum electrolytes and
osmolality. Expired air was collected for calculation of VO2 and respiratory
exchange ratio which were used to estimate rates of fuel oxidation. Ratings of
perceived exertion (RPE) were also obtained. Exercise capacity was not different
(P=0.49) between trials, with median (range) times to exhaustion of 90.6 (66.8
106.0), 97.7 (60.9-112.0) and 102.0 (77.1-170.7) min for the ND, 15% CHO and 2%
CHO trials, respectively. The 15% CHO drink significantly (P < 0.05) elevated
blood glucose concentration and total CHO oxidation compared with the ND trial.
The 2% CHO drink significantly (P < 0.05) reduced the estimated change in plasma
volume and resulted in a lower serum osmolality than the other two trials. No
differences were observed in any thermoregulatory or cardiorespiratory responses
between trials. These data suggest that maintenance of blood-borne substrate
and/or plasma volume does not influence exercise capacity in the cold, as is
commonly reported during this type and intensity of exercise in warmer
environments.
PMID- 9639352
TI - Measurement of nitric oxide concentration in human skin in vivo using dermal
microdialysis.
AB - Using microdialysis, we measured nitric oxide (NO) levels in healthy human skin,
in vivo, before and during the local inflammatory response to histamine. Basal
dialysate NO concentration, assayed using an amperometric technique, was 0.49+/
0.06 microM (mean+/-S.E.M., 21 probes, 14 subjects). Histamine injection produced
transient increases in NO concentration within both the weal and flare which was
blocked by the NO synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME).
Dialysate NO concentration also increased following transdermal delivery of the
nitrosovasodilator, glyceryl trinitrate. Thus, using microdialysis, it is
possible to quantify NO production in human skin in vivo and study its modulation
during the acute inflammatory response.
PMID- 9639353
TI - Unequal cleavage in the early Tubifex embryo.
AB - Unequal cleavage that produces two blastomeres of different size is a cleavage
pattern that many animals in a variety of phyla, particularly in Spiralia, adopt
during early development. This cleavage pattern is apparently instrumental for
asymmetric segregation of developmental potential, but it is also indispensable
for normal embryogenesis in many animals. Mechanically, unequal cleavage is
achieved by either simple unequal cytokinesis or by forming a polar lobe at the
egg's vegetal pole. In the present paper, the mechanisms for unequal cytokinesis
involved in the first three cleavages in the oligochaete annelid Tubifex are
reviewed. The three unequal cleavages are all brought about by an asymmetrically
organized mitotic apparatus (MA). The MA of the first cleavage is monastral in
that an aster is present at one pole of a bipolar spindle but not at the other.
This monastra form, which arises as a result of the involvement of a single
centrosome in the MA assembly, is both necessary and sufficient for unequal first
cleavage. The egg cortex during the first mitosis is devoid of the ability to
remodel spindle poles. In contrast to the non-cortical mechanisms for the first
cleavage, asymmetry in the MA organization at the second and third cleavages
depends solely on specialized properties of the cell cortex, to which one spindle
pole is physically connected. A cortical attachment site for the second cleavage
spindle is generated de novo at the cleavage membrane resulting from the first
cleavage; it is an actin-based, cell contact-dependent structure. The cortical
microtubule attachment site for the third cleavage, which functions independently
of contact with other cells, is not generated at the cleavage membrane resulting
from the second cleavage, but is located at the animal pole; it may originate
from the second polar body formation and become functional at the 4-cell stage.
PMID- 9639354
TI - Dorsal specification in blastoderm at the blastula stage in the goldfish,
Carassius auratus.
AB - The teleost dorsoventral axis cannot be morphologically distinguished before
gastrulation. Previous studies by the current authors have shown that localized
dorsalizing activity in the yolk cell (YC) induces the dorsal tissues in the
overlying blastoderm. In order to examine whether or not dorsal blastomeres are
committed to their dorsal fate before the gastrula stage, a variety of transplant
operations were performed in goldfish blastoderms at the mid- to late-blastula
stages. When the blastoderm was cut from the YC, rotated horizontally at 180
degrees, and recombined with the YC, the blastoderm frequently developed two
axes, indicating that dorsal blastomeres of the blastula had already acquired the
ability to differentiate into the organizer in the absence of dorsalizing signals
from the YC. This result was further confirmed by experiments using ventralized
embryos in which no dorsal structures formed: the axis formation was frequently
observed in the normal blastoderm combined with the ventralized YC at the
blastula stage. However, the axes formed in the absence of dorsal information
from the YC exhibited a lower dorso-anterior index. Furthermore, the dorsal
specification was not stably maintained when the dorsal cells were located far
from the YC. These results suggest that the inductive and permissive influence of
the YC may be required for the blastoderm to undergo full dorsal differentiation.
PMID- 9639355
TI - Embigin/basigin subgroup of the immunoglobulin superfamily: different modes of
expression during mouse embryogenesis and correlated expression with carbohydrate
antigenic markers.
AB - Embigin and basigin are highly glycosylated transmembrane glycoproteins with two
immunoglobulin domains and form a subgroup in the immunoglobulin superfamily.
Previous studies have demonstrated the functional significance of these
molecules. In the present study, in situ hybridization analysis of their
expression was performed during mouse embryogenesis. Embigin was strongly
expressed in the endoderm during early postimplantation embryogenesis, and in the
somite stage in the gut and visceral endoderm. Embryonic ectoderm and its
derivative tissues weakly to moderately expressed this molecule. From day 10 to
15 of gestation, no embigin signal was detected. Basigin was more broadly
expressed. During the organogenesis period, basigin was expressed in various
epithelial tissues, brain ventricles, the spinal cord and dorsal root ganglion.
The modes of expression of these two proteins throughout the egg cylinder stage
correlated with the expression of the carbohydrate markers that they carry;
embigin with Dolichos biflorus agglutinin binding sites and basigin with LeX
antigen and more closely with fucosyltransferase IV, which forms the antigenic
epitope. These findings imply that proteins with specific carbohydrate epitopes
play roles in early postimpantation embryogenesis.
PMID- 9639356
TI - Initial analysis of the molecular image of pamlin, a sea urchin cell adhesion
protein, by transmission electron microscopy.
AB - Pamlin, an important extracellular protein required early for sea urchin
embryogenesis, is readily isolated from the embryos of Hemicentrotus
pulcherrimus. A molecular image analysis of pamlin was conducted using immuno
electron microscopy, rotary shadowing and negative staining technique-applied
electron microscopy. The electron microscopy showed that a monoclonal antibody to
the pamlin alpha-subunit bound to a position 13.5 nm from one end of a purified
255 kDa pamlin molecule, which is a 132 nm long and 6.8 nm wide linear structure.
The pamlin structure is composed of three subunits, a 47 nm long 52 kDa alpha
subunit that attaches to one end of a 105 nm long 180 kDa beta-subunit, and a
15.6 nm diameter globular 23 kDa gamma-subunit that binds to the middle of the
beta-subunit. The alpha- and beta-subunits together form a 125-140nm linear
structure. Intermolecular aggregation frequently occurred between the free end of
two beta-subunits of the alphabetagamma pamlin molecule, leaving the entire alpha
subunit surface free. Occasionally associations between the ends of alpha
subunits, or between an alpha-subunit and the middle of a beta-subunit also
occurred, but no aggregations of pamlin formed through the gamma-subunit. These
homophilic molecular aggregations of pamlin formed a large supramolecular
network. In addition, the single pamlin molecule rounded at one end under high
calcium ion concentration to form a 'loop', suggesting the presence of a calcium
sensitive region in the molecule.
PMID- 9639357
TI - Effects of wheat germ agglutinin on tunicate egg activation and fertilization: is
there a plasma membrane sperm receptor system on Ascidia ceratodes eggs?
AB - Little work has been carried out on the sperm recognition systems present on the
egg plasma membrane. Here it is shown that wheat germ agglutinin (WGA) interferes
with the sperm-interacting system on the plasma membrane of eggs of the ascidian,
Ascidia ceratodes. The WGA activates the dechorionated egg, indicating that a
plasma membrane sugar residue can be directly tied to egg activation. Low
concentrations of this lectin do not activate the eggs, but reduce
fertilizability. This observation suggests that the WGA binding site might be
part of a sperm reception-activation complex in the plasma membrane. While WGA
also affects sperm binding to the chorion, the mechanisms of sperm interaction at
the plasma membrane and chorion show different sensitivities to lectins, sugars
and enzymes.
PMID- 9639358
TI - Induction of metamorphosis in the sand dollar Peronella japonica by thyroid
hormones.
AB - The larva of the sand dollar Peronella japonica lacks a mouth and gut, and
undergoes metamorphosis into a juvenile sand dollar without feeding. In the
present study, it was found that thyroid hormones accelerate the metamorphosis of
P. japonica larvae. The contents of thyroid hormones in larvae increased
gradually during development. Thiourea and potassium perchlorate, inhibitors of
thyroid hormone synthesis, delayed larval metamorphosis and simultaneously
repressed an increase in the content of thyroxine in the larval body. These
results suggest that the P. japonica larva has a system for synthesis of thyroid
hormones that act as factors for inducing metamorphosis.
PMID- 9639359
TI - Calcium transients accompany ooplasmic segregation in zebrafish embryos.
AB - Through the injection of f-aequorin (a calcium-specific luminescent reporter),
and the use of an imaging photon detector, transient localized elevations of free
cytosolic calcium in the forming blastodisc (BD) and animal hemisphere cortex
were visualized that correlated with ooplasmic segregation. The introduction of
an appropriate concentration of the weak (KD = 1.5 micromol/L) calcium buffer
5,5'-dibromo-BAPTA results in the dissipation of these calcium domains, and
inhibits cytoplasmic streaming and the subsequent formation of a BD at the animal
pole. These inhibitory actions are dependent on the final cytosolic concentration
of buffer within the egg: > or = 1.3 mmol/L blocks ooplasmic streaming; < 1.3
mmol/L eggs segregate normally. Injection of 5,5'-dimethyl-BAPTA (KD = 0.15
micromol/L) to a final concentration of 1.5 mmol/L as a control has no effect on
ooplasmic streaming. These results suggest that localized domains of elevated
free cytosolic calcium are essential for ooplasmic segregation in zebrafish.
Furthermore, a hypothetical model is presented linking these calcium transients
to the contraction of a cortically located actin microfilament network as a
possible mechanism providing the driving force for segregation.
PMID- 9639360
TI - Effects of mesenchyme on epithelial tissue architecture revealed by tissue
recombination experiments between the submandibular gland and lung of embryonic
mice.
AB - Lung epithelium during morphogenesis maintains a sheet structure of polarized
cells lining a lumen, in which E-cadherin, beta-catenin and tight junctional
proteins are localized at the cell-cell contact sites. On the other hand, the
submandibular gland epithelium at early stages of development forms a non
cavitated mass of cells where E-cadherin/beta-catenin are present on the entire
cell surfaces and tight junctional proteins are almost absent or weakly
scattered. In the present study, tissue recombination experiments were performed
between the two organs to explore roles of mesenchyme in the architectural
development of the epithelium. Homotypic recombinants of both submandibular gland
and lung showed the tissue architecture as observed in the intact organs. In
contrast, 11-day lung epithelium cultured with 13-day submandibular mesenchyme
formed multilayers of cells with the lumen being less visible. It was accompanied
by redistribution of E-cadherin/beta-catenin along the entire cell surfaces and
by an irregular distribution of tight junctional proteins. A similar
redistribution of these molecules was observed in 15-day lung epithelium cultured
with the submandibular mesenchyme, although the epithelial sheet structure lining
the lumen was formed. On the other hand, the tissue architecture of submandibular
gland epithelium was little affected by lung mesenchyme, although the epithelium
was flattened and showed branching morphogenesis.
PMID- 9639361
TI - Patterns of gene expression in the core of Spemann's organizer and activin
treated ectoderm in Cynops pyrrhogaster.
AB - The presumptive pharyngeal endoderm region of the Cynops early gastrula induces
head or trunk-tail structures in sandwich culture. Activin-treated ectoderm can
mimic this phenomenon at least at the histological level. The patterns of
expression of organizer-specific genes were examined to compare these two
inductive materials at the molecular level. A chordin cDNA clone from Cynops
pyrrhogaster (Cychd) was isolated by reverse transcription-polymerase chain
reaction (RT-PCR). Cychd mRNA was first detected in the presumptive pharyngeal
endoderm and prechordal plate regions of stage 11 embryos, and was expressed
continuously until stage 20. The spatiotemporal expression pattern of Cychd was
similar to that of Xenopus chordin. The patterns of expression of organizer
related genes in the pharyngeal endoderm and activin-treated ectoderm were
compared by RT-PCR analysis. Expression of Cychd in these two materials peaked at
the time when they can induce head structures in sandwich culture. Expression of
fork head and goosecoid did not change in the presumptive pharyngeal endoderm
over this period. Cychd may play a key role in head formation in the Cynops
embryo.
PMID- 9639363
TI - Existence of gradient in cell adhesiveness along the developing Xenopus hind limb
bud, shown by a cellular sorting-out experiment in vitro.
AB - To examine the possibility of a difference in cell adhesiveness along the
developing Xenopus hind limb bud axes, single mesenchymal cells from developing
hind limb buds were cultured, allowing them to form an aggregate in a gyratory
culture system. By observing the distribution of cells within aggregates, it was
found that sorting-out occurred between cells from different positions and
different stages. Cells derived from more distal positions tended to be situated
interiorly in the aggregates. According to Steinberg's differential adhesion
hypothesis, these results support the idea that there is a graded difference in
cell adhesiveness along the proximo-distal axis of the developing limb, with
adhesiveness increasing distally. Although similar sorting-out was observed
between anterior and posterior cell populations, it could not be determined which
cell populations were definitely more cohesive. These properties may be
correlated with the experimentally demonstrated 'positional value', which should
be different among cells located at different positions along the axes of the
developing vertebrate limb bud.
PMID- 9639362
TI - Sequence and expression of a novel mouse gene PRDC (protein related to DAN and
cerberus) identified by a gene trap approach.
AB - Gene trapping in embryonic stem (ES) cells was used to identify a novel gene
involved in mouse development. In order to screen trapped ES cell lines for the
presence of developmentally regulated genes, an in vitro differentiation test was
used. One of the G418 resistant cell lines, in conjunction with the lacZ reporter
gene, showed differential expression patterns under differentiated and
undifferentiated conditions. The gene trap insertion in this cell line was germ
line transmitted and X-gal staining was used to assess the expression pattern of
lacZ in embryos heterozygous for the trapped allele. The reporter gene's
expression was detected in commissural neurons in the developing spinal cord,
suggesting functions for the trapped gene in mouse neural development. Structural
analysis of the cDNA revealed that this trapped gene, named PRDC (protein related
to DAN and cerberus), is a novel gene that encodes a putative secretory protein
consisting of 168 amino acid residues. PRDC gene product shows limited
similarities to the products of DAN (differential screening-selected gene
aberrative in neuroblastoma) and cerberus. (DAN is a possible tumor-suppressor
for neuroblastoma in human. Cerberus can induce an ectopic head in Xenopus
embryos when ectopically expressed.) These three gene products may form a novel
family of signaling molecules.
PMID- 9639364
TI - Hantavirus pulmonary syndrome--Colorado and New Mexico, 1998.
AB - Hantavirus pulmonary syndrome (HPS) is a severe cardiopulmonary illness resulting
in death in approximately 45% of cases. The most frequently recognized etiologic
agent of HPS in North America, Sin Nombre virus (SNV), is transmitted to humans
from its primary rodent reservoir, Peromyscus maniculatus (deer mouse), by direct
contact with infected rodents, rodent droppings, or nests or through inhalation
of aerosolized virus particles from mouse urine and feces. Sporadic cases occur
throughout the United States and Canada, but the potential for spread from
rodents to humans in 1998 probably has increased because of increased rodent
population densities in some regions of the country. This report describes three
cases of HPS that occurred in the southwestern United States with onsets of
illness during April 15-28, 1998, and recommends methods to avoid exposure to
rodents inside and around human dwellings.
PMID- 9639365
TI - Deaths associated with occupational diving--Alaska, 1990-1997.
AB - During 1989-1997, the Occupational Safety and Health Administration (OSHA)
recorded 116 occupational diving fatalities in the United States (OSHA,
unpublished data, 1998). During 1990-1997, nine persons in Alaska died in work
related diving incidents (four were investigated by OSHA); only one had training
beyond a recreational diving certificate, and three lacked any certification. In
response to concerns about adequate training of occupational divers in Alaska and
recent public inquiry, CDC's National Institute for Occupational Safety and
Health (NIOSH) reviewed the nine occupational diving fatalities in Alaska. This
report describes three of these incidents, summarizes the results of the review,
and provides recommendations to improve the safety of commercial diving.
PMID- 9639366
TI - Community exposure to toluene diisocyanate from a polyurethane foam manufacturing
plant--North Carolina, 1997.
AB - In August 1996, residents of a community in Randolph County, North Carolina,
contacted the Agency for Toxic Substances and Disease Registry (ATSDR) because of
health concerns about possible exposure to chemical emissions from a polyurethane
manufacturing plant. ATSDR and the North Carolina Department of Environment,
Health, and Natural Resources (NCDEHNR) conducted ambient air monitoring to
characterize air contamination near the plant. ATSDR and Randolph County health
officials also conducted biologic monitoring to determine whether residents were
being exposed to toluene diisocyanate (TDI) emitted from the plant. This report
summarizes the results of these investigations, which indicate that residents
were being exposed to TDI in ambient air surrounding the plant.
PMID- 9639367
TI - Outbreak of Vibrio parahaemolyticus infections associated with eating raw oysters
-Pacific Northwest, 1997.
AB - During July-August 1997, the largest reported outbreak in North America of
culture-confirmed Vibrio parahaemolyticus infections occurred. Illness in 209
persons was associated with eating raw oysters harvested from California, Oregon,
and Washington in the United States and from British Columbia (BC) in Canada; one
person died. This report summarizes the investigations of the outbreak, which
suggest that elevated water temperatures may have contributed to increased cases
of illness and highlights the need for enhanced surveillance for human
infections.
PMID- 9639368
TI - Multistate outbreak of Salmonella serotype Agona infections linked to toasted
oats cereal--United States, April-May, 1998.
AB - During April-May 1998, a total of 11 states reported an increase in cases of
Salmonella serotype Agona infections; as of June 8, a total of 209 cases have
been reported and at least 47 persons have been hospitalized, representing an
eightfold increase over the median number of cases reported in those states
during 1993-1997. The states reporting increases were Illinois (49 cases),
Indiana (30), Ohio (29), New York (24), Missouri (22), Pennsylvania (20),
Michigan (15), Iowa (eight), Wisconsin (six), Kansas (four), and West Virginia
(two). This report summarizes the outbreak investigation by local, state, and
federal public health officials, which implicated Millville brand plain Toasted
Oats cereal manufactured by Malt-O-Meal, Inc. as the cause of illness.
PMID- 9639369
TI - Measles, mumps, and rubella--vaccine use and strategies for elimination of
measles, rubella, and congenital rubella syndrome and control of mumps:
recommendations of the Advisory Committee on Immunization Practices (ACIP).
AB - These revised recommendations of the Advisory Committee on Immunization Practices
(ACIP) on measles, mumps, and rubella prevention supersede recommendations
published in 1989 and 1990. This statement summarizes the goals and current
strategies for measles, rubella, and congenital rubella syndrome (CRS)
elimination and for mumps reduction in the United States. Changes from previous
recommendations include: Emphasis on the use of combined MMR vaccine for most
indications; A change in the recommended age for routine vaccination to 12-15
months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A
recommendation that all states take immediate steps to implement a two dose MMR
requirement for school entry and any additional measures needed to ensure that
all school-aged children are vaccinated with two doses of MMR by 2001; A
clarification of the role of serologic screening to determine immunity; A change
in the criteria for determining acceptable evidence of rubella immunity; A
recommendation that all persons who work in health-care facilities have
acceptable evidence of measles and rubella immunity; Changes in the recommended
interval between administration of immune globulin and measles vaccination; and
Updated information on adverse events and contraindications, particularly for
persons with severe HIV infection, persons with a history of egg allergy or
gelatin allergy, persons with a history of thrombocytopenia, and persons
receiving steroid therapy.
PMID- 9639370
TI - FDA Panel report: January 1998.
PMID- 9639371
TI - Load-dependent myocyte dysfunction.
PMID- 9639372
TI - Intracoronary infusion of reduced glutathione improves endothelial vasomotor
response to acetylcholine in human coronary circulation.
AB - BACKGROUND: Oxygen free radicals have been shown to cause endothelial vasomotor
dysfunction. This study examined the effect of reduced glutathione (GSH), an
antioxidant, on human coronary circulation. METHODS AND RESULTS: Responses of
epicardial diameter and blood flow of the left anterior descending coronary
artery to intracoronary infusion of acetylcholine (ACh, 50 microg/min) were
measured by quantitative coronary angiography and Doppler flow-wire technique,
respectively, before and during combined intracoronary infusion of GSH (50
mg/min) or saline in 26 subjects with no significant coronary stenosis. GSH
infusion suppressed the constrictor response of epicardial diameter to ACh and
enhanced the increase in blood flow response to ACh. Furthermore, GSH potentiated
the coronary dilator effect of nitroglycerin. A beneficial effect of GSH on the
epicardial diameter response to ACh was observed in a subgroup of subjects with >
or = 1 coronary risk factors but not in a subgroup without risk factors. Saline
infusion did not have any effects. CONCLUSIONS: The results indicate that GSH
improved coronary endothelial vasomotor function, particularly in subjects with
coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin
in human coronary arteries.
PMID- 9639373
TI - Angiographic assessment of myocardial reperfusion in patients treated with
primary angioplasty for acute myocardial infarction: myocardial blush grade.
Zwolle Myocardial Infarction Study Group.
AB - BACKGROUND: The primary objective of reperfusion therapies for acute myocardial
infarction is not only restoration of blood flow in the epicardial coronary
artery but also complete and sustained reperfusion of the infarcted part of the
myocardium. METHODS AND RESULTS: We studied 777 patients who underwent primary
coronary angioplasty during a 6-year period and investigated the value of
angiographic evidence of myocardial reperfusion (myocardial blush grade) in
relation to the extent of ST-segment elevation resolution, enzymatic infarct
size, left ventricular function, and long-term mortality. The myocardial blush
immediately after the angioplasty procedure was graded by two experienced
investigators, who were otherwise blinded to all clinical data: 0, no myocardial
blush; 1, minimal myocardial blush; 2, moderate myocardial blush; and 3, normal
myocardial blush. The myocardial blush was related to the extent of the early ST
segment elevation resolution on the 12-lead ECG. Patients with blush grades 3, 2,
and 0/1 had enzymatic infarct sizes of 757, 1143, and 1623 (P<0.0001),
respectively, and ejection fractions of 50%, 46%, and 39%, respectively
(P<0.0001). After a mean+/-SD follow-up of 1.9+/-1.7 years, mortality rates of
patients with myocardial blush grades 3, 2, and 0/1 were 3%, 6%, and 23%
(P<0.0001), respectively. Multivariate analysis showed that the myocardial blush
grade was a predictor of long-term mortality, independent of Killip class,
Thrombolysis In Myocardial Infarction grade flow, left ventricular ejection
fraction (LVEF), and other clinical variables. CONCLUSIONS: In patients after
reperfusion therapy, the myocardial blush grade as seen on the coronary angiogram
can be used to describe the effectiveness of myocardial reperfusion and is an
independent predictor of long-term mortality.
PMID- 9639374
TI - Apoptosis and related proteins in different stages of human atherosclerotic
plaques.
AB - BACKGROUND: The transition of a fatty streak into an atherosclerotic plaque is
characterized by the appearance of focal and diffuse regions of cell death. We
have investigated the distribution of apoptotic cell death and apoptosis-related
proteins in early and advanced atherosclerotic lesions. METHODS AND RESULTS:
Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy
specimens (n=18). This approach allowed comparison of adaptive intimal
thickenings, fatty streaks, and advanced atherosclerotic plaques of the same
patient. The fatty streaks differed from adaptive intimal thickenings by the
presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both
regions were composed mainly of smooth muscle cells (SMCs), and macrophage
infiltration was low and not different. Apoptosis, as detected by DNA in situ end
labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ
nick translation) was not present in these regions. Apoptosis of SMCs and
macrophages, however, was present in advanced atherosclerotic plaques that were
present mainly in the carotid sinus. A dense infiltration of macrophages (5.8+/
3% surface area) was present in these advanced atherosclerotic plaques.
Cytoplasmic remnants of apoptotic SMCs, enclosed by a cage of thickened basal
lamina, were TUNEL negative and remained present in the plaques as matrix
vesicles. CONCLUSIONS: We conclude that SMCs within human fatty streaks express
BAX, which increases the susceptibility of these cells to undergo apoptosis. The
localization of these susceptible SMCs in the deep layer of the fatty streaks
could be important in our understanding of the transition of fatty streaks into
atherosclerotic plaques, which are characterized by regions of cell death. Matrix
vesicles are BAX-immunoreactive cytoplasmic remnants of fragmented SMCs that can
calcify and may be considered the graves of SMCs that have died in the plaques.
PMID- 9639375
TI - Myocyte recovery after mechanical circulatory support in humans with end-stage
heart failure.
AB - BACKGROUND: The failing myocardium is characterized by decreased force
production, slowed relaxation, and depressed responses to beta-adrenergic
stimulation. In some heart failure patients, heart function is so poor that a
left ventricular assist device (LVAD) is inserted as a bridge to transplantation.
In the present research, we investigated whether circulatory support with an LVAD
influenced the functional properties of myocytes from the failing heart. METHODS
AND RESULTS: Myocytes were isolated from human explanted failing hearts (HF
myocytes) and failing hearts with antecedent LVAD support (HF-LVAD-myocytes).
Studies of myocyte function indicated that the magnitude of contraction was
greater (9.6+/-0.7% versus 6.9+/-0.5% shortening), the time to peak contraction
was significantly abbreviated (0.37+/-0.01 versus 0.75+/-0.04 seconds), and the
time to 50% relaxation was reduced (0.55+/-0.02 versus 1.45+/-0.11 seconds) in
the HF-LVAD-myocytes compared with the HF-myocytes (P<0.05). The HF-LVAD-myocytes
had larger contractions than the HF-myocytes at all frequencies of stimulation
tested. The negative force-frequency relationship of the HF-myocytes was improved
in HF-LVAD-myocytes but was not reversed. Responses to beta-adrenergic
stimulation (by isoproterenol) were greater in HF-LVAD-myocytes versus HF
myocytes. CONCLUSIONS: The results of the study strongly support the idea that
circulatory support with an LVAD improves myocyte contractile properties and
increases beta-adrenergic responsiveness.
PMID- 9639376
TI - Inhibition of neutral endopeptidase causes vasoconstriction of human resistance
vessels in vivo.
AB - BACKGROUND: Neutral endopeptidase (NEP) degrades vasoactive peptides, including
the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition
of NEP does not consistently lower blood pressure, even though it increases
natriuretic peptide concentrations and causes natriuresis and diuresis. We
therefore investigated the direct effects of local inhibition of NEP on forearm
resistance vessel tone. METHODS AND RESULTS: Four separate studies were
performed, each with 90-minute drug infusions. In the first study, 10 healthy
subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat
(125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/
2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours
after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP
inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local
forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%,
P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy
subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA
antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local
forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation
(33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/
1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive
patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30
nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/
2%, P=0.0001). CONCLUSIONS: Inhibition of local NEP causes vasoconstriction in
forearm resistance vessels of both healthy volunteers and patients with
hypertension. The lack of effect of ACE inhibition on the vasoconstriction
produced by thiorphan and its absence during concomitant ETA receptor blockade
suggest that it is mediated by endothelin-1 and not angiotensin II. These
findings may help to explain the failure of systemic NEP inhibition to lower
blood pressure.
PMID- 9639377
TI - Tachycardia-induced change of atrial refractory period in humans: rate dependency
and effects of antiarrhythmic drugs.
AB - BACKGROUND: Atrial fibrillation (AF) has been shown to shorten the atrial
effective refractory period (ERP) and make the atrium more vulnerable to AF. This
study investigated the effect of atrial rate and antiarrhythmic drugs on ERP
shortening induced by tachycardia. METHODS AND RESULTS: Seventy adult patients
without structural heart disease were included. For the first part of the study,
right atrial ERP was measured with a drive cycle length of 500 ms before and
after 10 minutes of rapid atrial pacing using five pacing cycle lengths (450,
400, 350, 300, and 250 ms) in 10 patients. For the second part of the study, the
remaining 60 patients were included to study the effects of antiarrhythmic drugs
on changes in atrial ERP induced by AF. Atrial ERP was measured with a drive
cycle of 500 ms before and after an episode of pacing-induced AF. After the
patients were randomized to receive one of six antiarrhythmic drugs
(procainamide, propafenone, propranolol, dl-sotalol, amiodarone, and verapamil),
atrial ERP was measured before and after another episode of pacing-induced AF. In
the first part of the study, atrial ERP shortened significantly after 10 minutes
of rapid atrial pacing, and the degree of shortening was correlated with pacing
cycle length. The second part of the study showed that atrial ERP shortened after
conversion of AF (172+/-15 versus 202+/-14 ms, P<0.0001) and that ERP shortening
was attenuated after verapamil infusion (-4.6+/-1.2% versus -15.1+/-3.4%,
P<0.001) but was unchanged after infusion of the other antiarrhythmic drugs.
Furthermore, all of these antiarrhythmic drugs could decrease the incidence and
duration of secondary AF. CONCLUSIONS: The atrial ERP shortening induced by
tachycardia was a rate-dependent response. Verapamil, but not other
antiarrhythmic drugs, could markedly attenuate this effect. However, verapamil
and the other drugs could decrease the incidence and duration of secondary AF.
PMID- 9639378
TI - Inducible nitric oxide synthase expression in smooth muscle cells and macrophages
of human transplant coronary artery disease.
AB - BACKGROUND: The inducible isoform of the nitric oxide synthase (iNOS) produces
large amounts of nitric oxide in response to cytokine stimulation. Previous
investigations have demonstrated iNOS expression in the setting of acute and
chronic rejection in experimental cardiac transplant models. The goal of this
study was to investigate whether iNOS is upregulated in human transplant coronary
artery disease (TCAD), a major cause of late mortality after cardiac
transplantation. METHODS AND RESULTS: We studied 15 patients with TCAD and 10
with normal coronary arteries. In situ hybridization and immunohistochemistry
were used in tissue sections to localize iNOS mRNA and protein, respectively. The
presence of peroxynitrite was indirectly assessed by immunostaining with an anti
nitrotyrosine antibody. Normal coronary arteries had no evidence of iNOS
expression. In contrast, 30 of 36 coronary artery segments with TCAD (83%) were
immunostained by the iNOS antibody. The presence of iNOS mRNA was demonstrated in
these vessels by in situ hybridization. Specific cell markers identified iNOS
positive cells as neointimal macrophages and smooth muscle cells. Nitrotyrosine
immunoreactivity colocalized with iNOS expression in arteries with TCAD,
distributed in macrophages and smooth muscle cells. CONCLUSIONS: iNOS mRNA and
protein are expressed in human arteries with TCAD, where they are associated with
extensive nitration of protein tyrosines. These findings indicate that the high
output nitric oxide pathway and possibly the oxidant peroxynitrite might be
involved in the process leading to the development of TCAD.
PMID- 9639379
TI - Role of endogenous endothelin in the development of graft arteriosclerosis in rat
cardiac allografts: antiproliferative effects of bosentan, a nonselective
endothelin receptor antagonist.
AB - BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET
1) contributes to the development of graft arteriosclerosis and whether the
orally active nonpeptide endothelin receptor antagonist bosentan, which blocks
both ETA and ETB receptors, can protect against this pathologic damage. METHODS
AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1
received heterotopic heart transplantations from Lewis donors and groups 2 and 3
received transplantations from Brown-Norway donors; group 3 recipients also
received bosentan orally at the dose of 20 mg/kg per day for 120 days. All
recipients were given cyclosporine and were euthanized at examination 120 days
after transplantation. Plasma ET-1 levels were significantly higher in group 2
than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1
immunoreactivity was seen in both the thickened neointima and the media of the
coronary arteries in group 2 but not in group 1. The mean ratio of the coronary
luminal area to the total vascular area in group 2 (19.0+/-11.7%) was
significantly lower than that in group 1 (34.2+/-9.9%) and was significantly
increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local
upregulation of ET-1, mainly in the thickened neointima and the media of the
coronary arteries, may play an important role in the pathogenesis of graft
arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally
active bosentan might be a useful agent for the clinical prevention of graft
arteriosclerosis.
PMID- 9639380
TI - Impaired modulation of sympathetic excitability by nitric oxide after long-term
administration of organic nitrates in pigs.
AB - BACKGROUND: Endogenous nitric oxide (NO) reduces sympathetic vasoconstriction by
attenuating neuronal excitability in the brain stem and inhibition of
postganglionic neurotransmission. We studied whether this modulation of
sympathetic circulatory control by NO may be altered during chronic
administration of NO donor drugs in pigs. METHODS AND RESULTS: Nitrate tolerance
was induced by oral administration of isosorbide dinitrate (ISDN, 4 mg/kg per day
for 4 weeks) in eight pigs. Four of them were chronically instrumented for the
measurement of mean arterial blood pressure and cardiac output in the conscious
state. ISDN treatment caused hemodynamic tolerance to NO donors and significantly
increased the hypotensive responses to pharmacologic ganglionic blockade in
conscious pigs. In general anesthesia, ISDN-treated animals and age-matched
controls (n=5) had similar baseline renal sympathetic nerve activity and in both
groups neither inhibition of NO synthases (NOS) nor administration of NO donors
to the brain stem by intracerebroventricular (i.c.v.) infusions caused
significant changes in baseline renal sympathetic nerve activity. However,
whereas sympathoexcitatory responses to glutamate (0.5 mL, 0.1 mol/L, i.c.v.) or
electrical stimulation of somatic nerve afferents were significantly potentiated
by central NOS inhibition and attenuated by NO donors in controls, these
treatments no longer had significant effects in ISDN-treated pigs. Furthermore,
reflex sympathetic activation in response to intravenous NO donor treatment was
more pronounced in nitrate tolerant animals, which suggests loss of central
sympathoinhibitory effects of NO. Subsequent histology on brain stem slices with
NADPH-diaphorase as NOS marker revealed significant reduction of NOS density in
ISDN-treated pigs. CONCLUSIONS: Long-term administration of organic nitrates
reduces the number of NO-producing neurons in the brain stem and causes loss of
inhibitory effects of NO on sympathetic excitability. This component of tolerance
to organic nitrates may be important in patients confronted frequently with
sympathetic activation caused by mental and/or physical stressors.
PMID- 9639382
TI - Dual-chamber pacing is superior to ventricular pacing: fact or controversy?
PMID- 9639381
TI - Dual-tracer assessment of coupling between cardiac sympathetic neuronal function
and downregulation of beta-receptors during development of hypertensive heart
failure of rats.
AB - BACKGROUND: Heart failure is associated with activation of the sympathetic
nervous system and downregulation of beta-receptors. However, the coupling
between cardiac sympathetic neuronal function and the beta-receptor during the
development of hypertensive heart failure is not clear. METHODS AND RESULTS: We
determined cardiac neuronal function and beta-receptors with a dual-tracer method
of [131I]metaiodobenzylguanidine (MIBG) and 125I-cyanopindolol (ICYP) in Dahl
salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl
diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12
weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR
rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but
deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE)
content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was
different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes
decreased, by 52% and 39%, respectively, in association with 71% reduction of
cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was
lower in the LV endocardial regions at 18 weeks in DS rats. CONCLUSIONS: The
present results indicate that cardiac sympathetic neuronal function is relatively
preserved at the compensated, hypertrophic stage of DS rats but deteriorates in
association with beta-receptor downregulation at the failing stage. The cardiac
neuronal dysfunction occurs heterogeneously. A combination of scintigraphic
portrayal of beta-receptors with MIBG should provide valuable information
regarding sympathetic nerve signaling in living hearts.
PMID- 9639383
TI - Images in cardiovascular medicine. Iron deposition in myocardium documented on
standard computed tomography in cardiac hemochromatosis.
PMID- 9639384
TI - Images in cardiovascular medicine. Coronary artery ectasia and systolic flow
cessation in hypertrophic cardiomyopathy.
PMID- 9639385
TI - Preferential allelic expression can lead to reduced expression of BRCA1 in
sporadic breast cancers.
AB - BRCA1 is considered to be a tumor-suppressor gene, yet mutations in this gene are
uncommon in sporadic breast tumors. We investigated whether mechanisms other than
DNA mutations that affect the coding region might be involved in breast
carcinogenesis. Since loss of expression of the BRCA1 gene would lead to lack of
protein, we evaluated the level of BRCA1 mRNA in 21 normal epithelial specimens
and in 74 breast carcinomas using quantitative reverse-transcription-polymerase
chain-reaction (RT-PCR). All normal breast epithelial samples expressed BRCA1
mRNA. On the other hand, the tumor specimens exhibited approximately 10-fold
range of levels of BRCA1, with some specimens expressing barely detectable
amounts of BRCA1 mRNA. The distribution in levels was significantly higher in
normal breast epithelial cells than in tumor specimens (p = 0.004). Examination
of the BRCA1 locus indicated that deletion of the BRCA1 gene may account for low
levels of BRCA1 in a number of specimens. In addition, analysis of samples with
relatively reduced levels of BRCA1 expression revealed preferential allele
specific expression in a number of cases, suggesting the presence of regulatory
mutations. Our data suggest that the BRCA1 gene may be involved in sporadic
breast carcinogenesis through a reduction in gene expression.
PMID- 9639386
TI - Quantitative analysis of Th1, Th2 and TGF-beta1 cytokine expression in tumor, TIL
and PBL of non-small cell lung cancer patients.
AB - For understanding the local immune response in human non-small cell lung cancer
(NSCLC), we investigated both Th1 and Th2-type as well as TGF-beta1 cytokine mRNA
expression in 10 fresh tumor biopsies, the corresponding tumor and short term TIL
cell lines as well as patient PBMC. A methodology based on a highly sensitive
quantitative RT-PCR was used. We found that IL-6 mRNA was highly expressed in all
tumor biopsy samples analyzed (4 LLC, 3 ADC and 3 SCC). IL-10 mRNA was expressed
in 7 of 10 biopsies whereas IL-4 mRNA expression was moderate. Analysis of type I
cytokines revealed a low expression level of IL-2 mRNA, while IFNgamma and GM-CSF
expression was high in the majority of the tumor lesions studied. Quantitatively,
high amounts of Th2-type cytokine mRNA were detected at the tumor site with IL-6
as the predominant lymphokine. A high mRNA expression level of the
immunosuppressive cytokine TGF-beta1 was observed in all NSCLC. To identify the
cell types responsible for the production of TGF-beta1, IL-6, IL-10 and GM-CSF at
the tumor site, tumor and TIL cell lines were derived from the corresponding
biopsies. All the 3 tumor cell lines analysed were found to express high amount
of TGF-beta1 but not IL-10 mRNA, 2 expressing IL-6 and GM-CSF. Five short term
TIL cell lines established in the presence of IL-2 expressed high level of IL-10,
IL-4 and IFNgamma but not IL-2 mRNA. Strikingly, high expression of IL-10 mRNA
was also observed in all 6 patient PBMC analyzed as compared to controls.
Together, our results indicate the existence of a local and peripheral Th-2-type
cytokine pattern in patients bearing NSCLC.
PMID- 9639387
TI - Perspectives of combined radioimmunotherapy and anti-EGFR antibody therapy for
the treatment of residual head and neck cancer.
AB - Rhenium-186 based radioimmunotherapy (RIT) may have potential for the treatment
of minimal residual disease in patients with squamous cell carcinoma of head and
neck (HNSCC). In an effort to enhance the efficacy of RIT, we evaluated the
combination of RIT and anti-epidermal growth factor receptor (EGFR) therapy in
nude mice bearing established HNSCC s.c. xenografts. For this purpose we used the
EGFR-blocking monoclonal antibody (MAb) 425. Treatment of HNSCC-bearing mice with
the combination of a single administration of 200 microCi 186Re-labeled MAb U36
as well as 1.1 mg unlabeled MAb 425 showed an enhanced efficacy in comparison to
the single treatments. When 500 microCi 186Re-labeled MAb U36 were administered,
all tumors eventually regressed completely. The combination of this RIT treatment
with multiple injections of MAb 425 significantly increased the rate of tumor
regression. Although RIT with 186Re-labeled MAbs appears to be very efficient on
HNSCC xenografts, the combination with anti-EGFR MAb 425 may enhance the
efficacy.
PMID- 9639388
TI - Expression of SSX genes in human tumors.
AB - The HOM-MEL-40 antigen which is encoded by the SSX-2 gene was originally detected
as a tumor antigen recognized by autologous IgG antibodies in a melanoma patient.
Expression analysis demonstrated that SSX-2 is a member of the recently described
cancer/testis antigen (CTA) class as it is expressed in a variety of different
human neoplasms, but not in normal tissues with the exception of testis and a
weak expression in the thyroid. Further studies demonstrated that SSX-2 belongs
to a gene family consisting of at least 5 homologous genes. We now report the
analysis of the expression of all 5 SSX genes in 325 specimens of human neoplasms
from various histological origins, using reverse transcription polymerase chain
reaction (RT-PCR). SSX-1, -2, and -4 were found to be expressed in 8%, 15% and
15%, of the tumors, respectively, while the expression of the SSX-5 gene was rare
(7/325), and SSX-3 expression was not detected. For defined tumor types,
expression of at least one of the SSX family members was most frequently observed
in head and neck cancer (75%), followed by ovarian cancer (50%), malignant
melanoma (43%), lymphoma (36%), colorectal cancer (27%) and breast cancer (23%),
while leukemias and the few cases of leiomyosarcomas, seminomas and thyroid
cancers were found not to express any SSX gene.
PMID- 9639389
TI - Whole grain food intake and cancer risk.
AB - The relationship between frequency of consumption of whole grain food and risk of
selected neoplasms has been analysed using data from an integrated series of case
control studies conducted in northern Italy between 1983 and 1996. The overall
dataset included the following incident, histologically confirmed neoplasms: oral
cavity and pharynx 181, oesophagus 316, stomach 745, colon 828, rectum 498, liver
428, gallbladder 60, pancreas 362, larynx 242, breast 3,412, endometrium 750,
ovary 971, prostate 127, bladder 431, kidney 190, thyroid 208, Hodgkin's disease
80, non-Hodgkin's lymphomas 200, multiple myelomas 120. Controls were 7,990
patients admitted to hospital for acute, non-neoplastic conditions, unrelated to
long-term modifications in diet and not likely to have been caused by tobacco or
alcohol use. Odds ratios (OR) for subsequent scores (never/occasional/frequent)
of whole grain food consumption were derived after allowance for age, sex,
education, smoking, alcohol intake and body mass index. High intake of whole
grain foods consistently reduced risk of neoplasm at all sites, except thyroid.
The ORs for the highest category of consumption were 0.2-0.3 for upper digestive
and respiratory tract neoplasms, 0.5 for stomach, colon and gallbladder, 0.7 for
rectum, 0.6 for liver, 0.8 for pancreas and prostate, 0.9 for breast and
endometrium, 0.6 for ovary, 0.4 for bladder and kidney, 1.3 for thyroid and
around 0.5 for lymphomas and myeloma. The tests for trend in risks were
significant for all neoplasms, except pancreas, endometrium, Hodgkin's disease
and multiple myeloma. No significant heterogeneity was found across strata of age
at diagnosis, sex, education, smoking habit, alcohol intake and body mass index.
Thus, even in the absence of a univocal and satisfactory biological
interpretation, the consistency of the patterns observed indicate that, in this
population, higher frequency of whole grain food intake is an indicator of
reduced risk of several neoplasms.
PMID- 9639390
TI - Risk factors for endometrial cancer according to familial susceptibility.
AB - Endometrial cancer (EC) shares some environmental or genetic risk factors with
colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is
the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis
colorectal cancer) and, in this syndrome, it has the same inheritance pattern as
CRC. Neoplastic family history and clinical features were evaluated in women with
EC in a health care district (Pordenone Province) in Northeastern Italy from 1990
to 1995, to examine the proportion of patients with hereditary cancer and the
relation with clinical characteristics of EC. We interviewed 215 patients with EC
(average age 61 years, range 35-88) in relation with some risk factors (age,
weight, diabetes, menstrual and reproductive pattern, synchronous and
metachronous neoplasms) and we obtained their family pedigree. Twenty-nine
patients (13.5%) had a CRC family history, 66 (30.7%) showed an aspecific cancer
aggregation in their families and more than half (120, 55.8%) had a negative
cancer family history. Family pedigrees were consistent with a dominant inherited
cancer pattern in 8 patients (3.7%) belonging to the CRC-related family history
group. A different pattern of family history distribution emerged in relation
with age (< 55 vs. > or = 55, p < 0.001) and body mass index (BMI) (< 26 vs. > or
= 26, p = 0.002). Patients with a CRC pedigree were more numerous in the younger
group, in the group with lower BMI and in pre-menopausal women.
PMID- 9639391
TI - Localization of CYP1A1 mRNA in human lung by in situ hybridization: comparison
with immunohistochemical findings.
AB - Cytochrome P4501A1 (CYP1A1) is involved in the bioactivation of polycyclic
aromatic hydrocarbons into their reactive epoxide metabolites. CYP1A1 is
considered to be important with regard to individual susceptibility to lung
cancer since phenotypic and genotypic polymorphisms of CYP1A1 have been
associated with an increased risk of lung cancer in a number of studies. We
examined here the expression and localization of CYP1A1 mRNA in human lung tissue
using in situ hybridization with a CYP1A1-specific RNA probe. A centrilobular
expression of CYP1A1 mRNA was observed in the peripheral lung. The expression was
intense in bronchiolar epithelium of peripheral lung, especially in terminal
cuboidal epithelium. Type II alveolar epithelial cells were also intensely
labelled. Type I alveolar epithelial cells and vascular epithelium exhibited
binding but the hybridization signals were less intense. Our results are in good
agreement with our previous work on immunohistochemical localization of CYP1A
protein, in which we used the 1-7-1 MAb that recognizes both CYP1A1 and CYP1A2.
In serial sections analyzed with in situ hybridization and immunohistochemistry,
a similar distribution of CYP1A1 mRNA and CYP1A protein was observed. CYP1A1 mRNA
is thus expressed in human lungs and the expression is particularly intense in
the cell types involved in the development of peripheral lung cancers.
PMID- 9639392
TI - Urinary excretion of 5-(hydroxymethyl) uracil in healthy volunteers: effect of
active and passive tobacco smoke.
AB - The urinary excretion of 5-(hydroxymethyl)uracil (5-HMUra), one of the major
oxidative modifications of thymine, was investigated in 134 healthy volunteers
living in North Italy. Overnight urine was collected, and a questionnaire was
completed on smoking habits and exposure to environmental tobacco smoke (ETS). 5
HMUra was analyzed by GC/MS, following urine purification by HPLC. 5-HMUra
excretion showed an approximately normal distribution, ranging from 0.08 to 0.84
(mean 0.44) nmoles/kg/8 hr and from 3.2 to 18.7 (mean 8.5) nmoles/mmoles
creatinine. 5-HMUra excretion was significantly higher in women than in men and
in smokers than in non-smokers when results were expressed as the ratio to
creatinine. Slightly higher levels of 5-HMUra excretion, expressed as
nmoles/mmoles creatinine, were also found in subjects highly exposed to ETS,
monitored either as the number of hours of exposure or as the number of smokers
in the workplace and at home. Our results show that the urinary excretion of 5
HMUra is higher than that of other oxidized nucleobases, including 8-oxo-7,8
dihydroguanine, and can be slightly modified by environmental factors such as
tobacco smoke. These findings suggest that measurement of urinary excretion of 5
HMUra could be useful as a biomarker of oxidative DNA damage and repair, though
further research is needed to support these data.
PMID- 9639393
TI - Adenovirus-mediated p16 gene transfer prevents drug-induced cell death through G1
arrest in human glioma cells.
AB - This study examined the effects of full-length p16 gene transfer by recombinant
adenovirus on cell growth and on sensitivity to CDDP or ACNU chemotherapies. We
developed a recombinant adenovirus expressing the full-length human p16 gene
(AxCA-hp16) by the COS-TPC method. AxCA-hp16 was infected into the p16-null human
glioma cell line, U251MG. AxCA-hp16 infection inhibited proliferation of U251MG
cells. A proliferation assay employing MTT showed that AxCA-hp16 infection
induced chemoresistance, preventing CDDP-induced cell death (11- to 15-fold) and
ACNU-induced cell death (80- to 92-fold). In the absence of AxCA-hp16, cell death
was induced with CDDP or ACNU at 3 to 5 days after treatment, as demonstrated by
Trypan-blue exclusion. Flow-cytometric analysis showed that CDDP or ACNU arrested
cells in the G2 phase on day 1 and that cells re-entered the cycle on day 3.
However, the cells infected with AxCA-hp16 after CDDP or ACNU treatment showed G1
arrest on day 5 after re-entering the cycle from G2 arrest on day 3. The cells
infected with AxCA-hp16 before CDDP or ACNU treatment showed G1 arrest over the 5
days after the infection. This study demonstrated that G1 arrest induced with p16
gene expression prevents ACNU- or CDDP-induced cell death. The cell death induced
by ACNU and CDDP therefore appears to occur in the phase after the G1/S check
point.
PMID- 9639394
TI - Changes in glutathione redox cycling and oxidative stress response in the
malignant progression of NB2 lymphoma cells.
AB - Differential analysis of closely related Nb2-lymphoma cell lines can be used for
identification of changes in biochemical properties associated with the malignant
progression of certain T-cell cancers. As tumors progress, they tend to show
metabolic alterations such as an increased resistance to oxidative stress, a
characteristic that may be correlated with changes in intrinsic antioxidant
levels (e.g., glutathione) and in activities of associated enzymes such as the
glutathione redox pathway. Whether increases in malignancy of Nb2 cells were
associated with changes in cellular glutathione levels and activities of
glutathione-metabolizing enzymes was addressed. To evaluate this relationship, 3
cell lines, showing increased malignancy, were used: Nb2-U17 (hormone-dependent,
non-metastatic), Nb2-11 (hormone-dependent, metastatic), Nb2-SFJCD1 (growth
factor-independent, metastatic). Compared to Nb2-U17 and Nb2-11 cells, the highly
progressed Nb2-SFJCD1 lymphoma cells maintain low basal glutathione levels.
However, the Nb2-SFJCD1 cells display an enhanced capacity to produce glutathione
when challenged with an oxidative stress and show a significantly higher
resistance to H2O2-induced apoptosis.
PMID- 9639395
TI - Reversal of multidrug resistance by the staurosporine derivatives CGP 41251 and
CGP 42700.
AB - It has been shown previously that the staurosporine derivative CGP 41251, a
specific inhibitor of protein kinase C (IC50 = 50 nM), exhibits antitumor
activity and reverses mdr1 mediated multidrug resistance. At present, the
compound is evaluated as an anticancer drug in clinical phase I trials. We
compared the effects of CGP 41251 with CGP 42700, another staurosporine
derivative, which exhibits low protein kinase C inhibiting activity (IC50 = > 100
microM). We found that in contrast to CGP 41251, CGP 42700 does not show
antiproliferative activity in HeLa and KB cells in tissue culture (up to a
concentration of 10 microM). We compared both compounds for their ability to
reverse mdr1-mediated resistance in KB-C1 and in HeLa-MDR1 cells (transfected
with the mdr1 gene). CGP 42700 is able to reverse mdr1-mediated resistance to a
similar extent as CGP 41251. The intracellular accumulation of rhodamine 123 in
KB-C1 cells following pretreatment with CGP 41251 for 30 min was higher than that
following treatment with CGP 42700 if determined in medium without serum.
However, quantitation of rhodamine efflux in an ex vivo assay using human CD8+
cells in serum showed that CGP 42700 is more effective in inhibiting the efflux
of rhodamine 123 than CGP 41251. We conclude from our results that (1) CGP 42700
is more effective in reversal of multidrug resistance in serum than CGP 41251,
indicating that the compound may be useful for treatment of patients, and (2) CGP
42700 does not inhibit protein kinase C and cell proliferation and, therefore,
may be less toxic and elicit less side effects in humans than other
chemosensitizers.
PMID- 9639396
TI - Sex- and strain-specific induction of renal tumors by ochratoxin A in rats
correlates with DNA adduction.
AB - Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, has been implicated
as an etiologic agent in the Balkan endemic nephropathy (BEN), a chronic disease
affecting populations in the Balkans. Compared with unaffected individuals,
patients suffering from BEN and/or urinary tract tumors were more frequently
found to have a capacity for rapid debrisoquine (DB) metabolism, a metabolic
reaction related mostly to cytochrome P450 (CYP) 2D in humans. Earlier studies,
using female DA and Lewis rats phenotyped as poor or extensive DB metabolizers
respectively, revealed a parallelism between DB-4 hydroxylation and OTA-4
hydroxylation. To investigate whether genetic polymorphism modifies tumor
induction, we have compared both OTA-induced renal carcinogenicity and DNA
adducts in DA and Lewis rats of both sexes. OTA induced renal adenocarcinoma, DA
male rats being most responsive, while DA females were resistant. Lewis rats
showed an intermediate renal tumor response. OTA also induced malignant
transitional cell carcinomas of the bladder in DA male rats only. DNA adducts in
the kidney, as judged by the nature of spots and prevalence in OTA-treated
animals, were significantly correlated with renal carcinogenicity of OTA, being
highest in DA males and lowest in DA females. A parallelism between karyomegalies
and tumors of the kidney was observed. In conclusion, our results classify OTA as
a genotoxic carcinogen in rats, with sex-specific response controlled in part by
drug-metabolizing enzymes that convert OTA into reactive intermediates.
PMID- 9639397
TI - Radiation-induced apoptosis in human tumor cell lines: adaptive response and
split-dose effect.
AB - Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI
8226) with graded doses of 137Cs-gamma-rays led to a 35-40% increase in time
dependent apoptosis 72 hr after 6-8 Gy irradiation. Large individual variations
in sensitivity to radiation-induced apoptosis were noted in human lymphocytes
obtained from 5 donors. Pretreatment of OVCAR 3 and RPMI 8226 cells with 0.01 Gy
increased their resistance to apoptosis after subsequent 6 Gy irradiation several
hours or 48 and 72 hr later. A dose of 4 or 8 Gy given in 2 equal fractions at an
interval of a few hours produced a low level of apoptosis compared to that
resulting from a single administration of the same total dose. Adaptive response
was demonstrated in 2 out of 3 samples of human lymphocytes isolated from
different donors, and no split-dose effect for apoptosis was noted in 2 other
donors. In split-dose experiments, there was no correlation between the
sensitivity of cells to apoptosis and their position in the cell cycle, after the
first half-dose. No G1 block was observed in irradiated cell lines. Adaptive
response and split-dose effect were prevented by 3-aminobenzamide and okadaic
acid which inhibit poly(ADP-ribose)polymerase and protein phosphatase,
respectively. These results imply a common mechanism for acquired resistance to
radiation-induced apoptosis in adaptive response and the split-dose effect.
PMID- 9639398
TI - Activation of MMP-2 by human GCT23 giant cell tumour cells induced by
osteopontin, bone sialoprotein and GRGDSP peptides is RGD and cell shape change
dependent.
AB - We show that osteopontin (OPN), bone sialoprotein (BSP) and GRGDSP peptides, in
solution, induce activation of metalloproteinase-2 (MMP-2) secreted by human
GCT23 giant cell tumour cells. Activation of MMP-2 is RGD sequence dependent,
possibly involves anti-alphaVbeta3 integrins, is preceded by a change from spread
to rounded cell morphology and is mimicked by the actin depolymerising agent
cytochalasin B. Cells that had spread on OPN, BSP and GRGDSP substrata failed to
activate MMP-2, but subsequent addition of soluble GRGDSP induced rounding and
MMP-2 activation. Activation induced by GRGDSP and cytochalasin B was cell
mediated, inhibited by EDTA, tissue inhibitor of metalloproteinase-2 (TIMP-2) and
carboxyl terminal MMP-2 consistent with a role for membrane type (MT)-MMP but did
not involve urokinase, plasmin or thrombin activity. Activation induced by GRGDSP
and cytochalasin B, but not cell rounding, was inhibited by herbimycin A,
cycloheximide and actinomycin D, suggesting a role for tyrosine kinases, protein
and RNA synthesis, but was not associated with changes in mRNA for MT-MMP-1, MMP
1, MMP-2, TIMP-1 or TIMP-2. GRGDSP and cytochalasin B enhanced levels of membrane
associated pro- and active form MMP-1 and MMP-2 but not MT-MMP-1, stimulated cell
surface MMP-1 staining and induced that of MT-MMP-1, MMP-2 and TIMP-2. This was
consistent with the possible relocation of constitutive MT-MMP-1 to the cell
surface as a prerequisite for subsequent cell surface MMP-2/TIMP-2/MT-MMP-1
complex formation and to the potential induction of conditions favourable for
reciprocal cell surface MMP-1/MMP-2 activation. Our data provide a novel insight
into interactions between RGD containing bone matrices, GCT cells and MMPs of
potential relevance to GCT pathology.
PMID- 9639399
TI - ras mutation and platinum resistance in human ovarian carcinomas in vitro.
AB - A panel of 16 human ovarian carcinoma cell lines comprising cisplatin naive as
well as those with acquired cisplatin resistance was studied to determine if
there was a relationship between ras status and cisplatin sensitivity. From the
ras expression studies alongside data produced by direct DNA sequencing, there
was very little to suggest that ras overexpression or mutation plays a role in
the cisplatin sensitivity of the panel of human ovarian carcinoma cell lines
tested. A weak correlation (r2 = 0.53) was found between total Ras protein levels
and resistance to cisplatin. No relationship was found between Kirsten-Ras
protein levels and cisplatin sensitivity (r2 = 0.0). Only one ras mutation (codon
13, Kirsten exon 1, glycine --> aspartate in the HX62 cell line) was observed in
the cisplatin naive cell lines from the panel which comprised both cisplatin
sensitive and resistant models. Of interest, however, was that the HX62 cell line
was the most resistant to cisplatin. No ras mutations were found in those cell
lines which had repeatedly been exposed, and acquired resistance, to cisplatin.
The A2780 and CH1 human ovarian carcinoma cell lines were transfected with
activated, mutant Harvey-ras and, as a result, were shown to display elevated MAP
kinase phosphorylation in low serum concentration growth medium. No changes in
cisplatin sensitivity were found following transfection with activated Harvey-ras
in these 2 human ovarian carcinoma tumor cell models which, importantly, differed
greatly in their expression of Bcl-2. Therefore, when conducted under similar
conditions to previously published studies, very little evidence was found to
support Harvey-ras activation as a factor which can either sensitize or confer
resistance to cisplatin in human ovarian carcinoma cell lines.
PMID- 9639400
TI - Enhanced sensitivity to tumor necrosis factor-alpha in doxorubicin-resistant
tumor cell lines due to down-regulated c-erbB2.
AB - We have studied the relationship between tumor necrosis factor (TNF)-sensitivity
and doxorubicin-resistance in our doxorubicin-resistant cell line panel
consisting of the parental cell line GLC4 plus GLC4-Adr2x and GLC4-Adr350x with
respective resistance factors of 2 and 350 compared with GLC4. At the highest
dose of 1000 ng/ml TNF, GLC4 was almost completely resistant to TNF, whereas 37%
and 68% growth inhibition was observed in GLC4-Adr2x and GLC4-Adr350x,
respectively. Sensitivity to TNF appeared to correlate inversely with the
expression and gene copies of topoisomerase IIalpha in these cell lines. The gene
encoding for c-erbB2 is in the proximity of the topoisomerase IIalpha gene and
its product is a known cause for TNF-resistance. We found that our doxorubicin
resistant cell lines with decreased topoisomerase IIalpha gene copies have a
simultaneous decrease in c-erbB2 gene copies, probably due to linkage between
these 2 genes. This reduced number of c-erbB2 gene copies resulted in decreased c
erbB2 expression and subsequently in increased sensitivity to TNF. Additionally,
we tried to establish some of the mechanisms associated with TNF-resistance in
GLC4 related to c-erbB2 overexpression. There was no difference in TNF-receptor-1
expression between the cell lines. Compared with the TNF-sensitive GLC4-Adr350x,
GLC4 appeared to have a decreased activation of NF-kappaB after exposure to TNF
that might indicate a reduced TNF-receptor function. In GLC4, increased Bcl-2
expression was found, a protein described to confer TNF-resistance. Moreover, it
was demonstrated that combining TNF with the poly-ADP-ribose polymerase (PARP)
inhibitors 6-aminonicotinamide and 3-aminobenzamide did not affect TNF
sensitivity in GLC4 and GLC4-Adr350x, excluding a pivotal role of PARP in TNF
resistance in these cell lines. In conclusion, our data show that doxorubicin
resistant tumor cell lines with decreased topoisomerase IIalpha gene copies can
become sensitive to TNF due to loss of c-erbB2 gene copies. We also found that
several mechanisms associated with c-erbB2 overexpressing contribute to TNF
resistance in GLC4.
PMID- 9639401
TI - Enhancement of the anti-tumor immune response using a combination of interferon
gamma and B7 expression in an experimental mammary carcinoma.
AB - In recent years, tumor immunotherapy has begun to exploit the emerging knowledge
of the mechanisms of T cell activation to enhance the immune responses to tumors.
However, many tumors, despite genetic modification to express co-stimulatory
molecules or cytokines, are not readily rejected due to their inherently poor
immunogenicity. In the present study, we tested whether expression of the co
stimulatory ligand B7-1 and the immunostimulatory cytokines interferon gamma (IFN
gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary
carcinoma (SM1) would sufficiently augment its immunogenicity to obtain rejection
and immunity. Our findings demonstrate that expression of B7, IFN-gamma, or GM
CSF alone, or co-expression of B7 and GM-CSF did not result in rejection of SM1.
However, co-expression of B7 and IFN-gamma was sufficient to result in regression
of SM1 tumors by a CD8+ T cell-dependent mechanism. Rejection of the B7/IFN-gamma
expressing SM1 tumor resulted in protection from rechallenge not only with the
unmodified SM1 tumor but with another syngeneic mammary tumor. Our data support
the idea that although B7 expression alone may not be sufficient for rejection of
certain tumors, the immune system may be stimulated to mount an effective anti
tumor immune response by the co-expression of both the co-stimulatory ligand and
a cytokine.
PMID- 9639402
TI - Antigen loss variants of a murine renal cell carcinoma: implications for tumor
vaccination.
AB - Vaccination with tumour cells genetically modified to support induction of an
immune response either by production of cytokines or expression of co-stimulatory
molecules provides a promising therapeutic approach. We have evaluated the
efficiency of tumour vaccination using RENCA cells, a renal cell carcinoma of the
BALB/c strain, which were stably transfected with MHC class II, B7.1 or both.
Tumour growth after vaccination with MHC class II and/or B7.1 transfected RENCA
cells was extremely variable, with protection close to 100% after vaccination
with some clones and no effect of vaccination with others. To unravel the
underlying mechanism, untransfected RENCA cells were cloned, and individual
clones were tested for immunogenicity; that cloned RENCA cells varied
considerably in immunogenicity. Whereas all clones displayed comparable growth
rates in nude mice, some grew very slowly in immunocompetent syngenetic hosts.
Vaccination with rapidly growing clones was ineffective and, importantly, this
feature remained unaltered by vaccination with MHC class II and/or B7.1
transfected clones. Instead, 8 of 10 mice rejected the parental line after
immunisation with a pool of MHC class II and B7.1 transfected clones. Finally, by
cloning RENCA cells, we obtained one highly immunogenic clone (P2). Vaccination
with this clone led to an individual-specific response, which indicates that
during the cloning procedure a new strongly immunogenic entity must have arisen.
Taken together, our results indicate that vaccination with MHC II and/or B7.1
transfected tumour cells induces an efficient immune response, but only if the
tumour is weakly immunogenic. Since tumours may be composed of clones displaying
different antigenicities, it is mandatory to use bulk cell populations for
transfection and vaccination.
PMID- 9639403
TI - Anti-prostate immunotoxins: cytotoxicity of E4 antibody-Pseudomonas exotoxin
constructs.
AB - E4 is a monoclonal antibody (MAb) that reacts with a surface antigen present on
normal prostate and prostate cancers. Using this antibody, 2 immunotoxins were
generated, one being a chemical conjugate with a mutant truncated form of
Pseudomonas exotoxin A (PE), E4-PE35KDEL. The other is a recombinant single chain
immunotoxin, E4(Fv)-PE38KDEL. The affinity of the conjugated immunotoxin was
similar to the hybridoma-produced MAb E4, revealing that conjugation did not
impair the binding ability. The affinity of the recombinant immunotoxin (10 nM)
was 10-fold lower than that of the MAb, probably reflecting differences of
bivalent (MAb) vs. monovalent (Fv) binding. Antigen positive prostate, breast and
colon carcinoma cell lines showed cytotoxic response to the E4 immunotoxins while
antigen negative cells were not affected. The IC50 value, representing a 50%
inhibition of cellular protein synthesis, ranged from 0.3 to 20 ng/ml for E4
PE35KDEL and from 2 to 100 ng/ml for E4(Fv)-PE38KDEL. Therefore, the E4-derived
immunotoxins may be useful for the treatment of prostate as well as breast and
colon cancers.
PMID- 9639404
TI - The Ets-1 and Ets-2 transcription factors activate the promoters for invasion
associated urokinase and collagenase genes in response to epidermal growth
factor.
AB - Urokinase plasminogen activator (uPA) has been associated with invasion and
metastasis in breast cancer. The expression of uPA and 92 kDa type IV collagenase
(gelatinase B/MMP-9) is regulated by growth factors, receptor-type tyrosine
kinases and cytoplasmic oncoproteins. Here, we have identified transcriptional
requirements for the induction of uPA and 92 kDa type IV collagenase by epidermal
growth factor (EGF). EGF stimulates the motile and invasive activities
specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of
extracellular matrix-degrading proteases including type I collagenase/MMP-1, 92
kDa type IV collagenase/MMP-9, uPA and uPA receptor were induced. EGF also
transiently stimulated expression of the transcription factors Ets-1 and Ets-2.
Reporter transfection assays revealed the activation of uPA and MMP-9 collagenase
promoters by EGF and the requirement of each of the composite Ets and AP-1
transcription factor binding sites for an EGF response. Most notably,
transfections with the Ets-1 and Ets-2 expression vectors potentiated uPA and MMP
9 promoter activation in response to EGF. Mutation of the threonine 75 residue of
chicken Ets-2 conserved in the Pointed group of the Ets family proteins abrogated
the ability of Ets-2 to collaborate with EGF. Ets-1 and Ets-2 were highly
expressed in invasive breast tumor cell lines. Our results suggest that Ets-1 and
Ets-2 provide the link connecting EGF stimuli with activation of uPA and 92 kDa
type IV collagenase promoters and may contribute to invasion phenotypes.
PMID- 9639405
TI - IFNgamma induction of p21WAF1 in prostate cancer cells: role in cell cycle,
alteration of phenotype and invasive potential.
AB - Type I and type II interferons (IFNs) are known to exert antitumor effects on a
variety of tissues and cell types. We have previously shown that the type I IFN
IFN alpha induces the expression of the cyclin-dependent kinase inhibitor p21WAF1
and inhibits the cell cycle of the human prostate adenocarcinoma cell line,
DU145, that carries mutations in the tumor suppressor gene products p53 and pRB.
We now show that the type II IFN IFN gamma similarly induces the expression of
p21WAF1 and inhibits the cell cycle of DU145 cells. In addition, we show that
while both IFNs exert antiproliferative activity, only IFN gamma induced
phenotypic changes in these cells that accompanied the antiproliferative effect.
For example, IFN gamma, but not IFN alpha, caused a significant reduction in
epidermal growth factor receptor expression as well as an increase in the
adhesion molecules intercellular adhesion molecule-1 and integrin alpha3. These
phenotypic changes in DU145 cells are suggestive of the acquisition of a non
tumorigenic state. Consistent with these findings, IFN gamma showed a
significantly lower invasive ability in in vitro assays using invasion chambers.
Thus, IFN gamma inhibits both the cell cycle and the metastatic potential of
DU145 cells independent of the p53 and RB status, and our data describe a
mechanism for mediating the antitumor capabilities of IFN gamma that bypasses
tumor suppressor genes like p53.
PMID- 9639406
TI - Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol
in endothelial cells.
AB - The anti-tumor drug Flavopiridol is a potent inhibitor of cyclin-dependent
kinases (cdks). As a consequence, Flavopiridol-treated cells arrest in both G1
and G2, but Flavopiridol has also been shown to be cytotoxic for some tumor cell
lines. The underlying molecular events are, however, unclear. We now show that
Flavopiridol induces apoptosis in human umbilical vein endothelial cells
(HUVECs), as judged by the occurrence of classical apoptotic markers, including
chromatin condensation, internucleosomal cleavage, DNA fragmentation (TUNEL
assay), annexin V binding and poly(ADP-ribose) polymerase (PARP)-cleavage. Such
induction of apoptosis occurs with equal efficiency in both proliferating and
G0/G1-arrested cells. Because growth-arrested HUVECs lack cdk2 activity and
contain high levels of the cdk inhibitor p27, our observations suggest that cell
cycle regulated cdks may not be the only critical target for Flavopiridol-induced
apoptosis. Surprisingly, A549 lung carcinoma cells were clearly dependent on cell
proliferation for the induction of cell death, pointing to cell type-related
differences in the mechanism of Flavopiridol action.
PMID- 9639407
TI - Antisense inhibition of urokinase: effect on malignancy in a human osteosarcoma
cell line.
AB - Expression of urokinase-type plasminogen activator (u-PA) strongly correlates
with a malignant tumor cell phenotype. In the multistep process of metastasis,
different cellular functions are influenced by urokinase. The enzyme is known to
be effective via both proteolytical and signal transduction mechanisms. In the
present study, the osteosarcoma cell line MNNG/HOS was transfected with a vector
capable of expressing an antisense transcript, complementary to 1,021 bases of
the 3' end of u-PA cDNA. This construct was most effective in reducing u-PA
expression in previous experiments. Stably transfected antisense (as) cell lines
were characterized and compared with the parental MNNG/HOS. Antisense
transfection of MNNG/HOS gave the following results: (1) stable incorporation of
the construct into the genome of as-clones, as detected by Southern blot
analysis; (2) decreased mRNA level of u-PA, as detected by Northern blot
analysis; (3) approximately 50% reduced enzyme expression in cell culture medium
and cell homogenate; and (4) unchanged cellular proliferation activity and u-PAR
expression. In further functional analysis, as-clones showed (1) significantly
reduced invasion and motility in modified Transwell chambers (random migration
and chemotaxis with collagen I as a chemoattractant); (2) significantly reduced
adhesion on matrices of collagen I and vitronectin; (3) unchanged adhesion
properties on Matrigel matrix; and (4) reduced metastatic potential to lungs and
especially liver in chick embryos after i.v. infection into chorioallantoic
membrane veins. Our data show that in MNNG/HOS urokinase influences cellular
malignancy by promoting migration and selective adhesion. These specific
functions were notable in addition to the effects on invasion and basement
membrane degradation.
PMID- 9639408
TI - Sensitivity or specificity of reverse transcriptase-polymerase chain reaction
assays: the real challenge for molecular staging of prostatic carcinomas.
PMID- 9639409
TI - Detection of illegitimate transcripts of prostate-specific antigen mRNA in blood
by reverse transcription-polymerase chain reaction.
PMID- 9639410
TI - Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes
p15, p16, p18 and p19 in human leukemia-lymphoma cells.
AB - The cyclin-dependent kinase inhibitors known as p15, p16, p18 and p19 have been
suggested as candidates for tumor suppressor genes. The main genetic alterations
are deletions (bi- or monoallelic) or 5' CpG island methylation of p15 and p16;
very few cases or cell lines had p18 or p19 deletions or hypermethylation.
Hypermethylation and homozygous deletions of tumor suppressor genes establish a
new paradigm of inactivation by lack of expression, in contrast to the previously
identified tumor suppressors which are predominantly inactivated by point
mutations followed by loss of the wild-type allele. Here, the literature data on
alterations of this gene family in more than 4700 primary cases of leukemia or
lymphoma and some 320 continuous leukemia-lymphoma cell lines are summarized.
Among hematopoietic malignancies, the highest frequencies of p15del and p16del
were seen in acute lymphoblastic leukemia (ALL) (>30%) with striking rates in T
ALL (>50%), but also high rates in B cell precursor (BCP)-ALL (>20%); the rates
of deletions in chronic lymphoid leukemia (CLL), multiple myeloma, acute and
chronic myeloid leukemia (AML and CML), and myelodysplastic syndromes (MDS) were
rather low, only some B cell and T cell lymphomas showed increased frequencies.
Results are quite different with regard to the second mode of inactivation,
hypermethylation of the promoter region. Here, p15 is most often inactivated, at
particularly high frequencies in the disorders lacking any p15/p16 deletions: 40
80% p15met in AML, MDS and multiple myeloma. Also p15met rates in BCP- and T-ALL
cases were high (c. 40%). There is controversy concerning the prognostic impact
of p15 and p16 aberrations with some studies describing a significant correlation
between inactivation of these genes and poor prognosis, while most others did not
detect any prognostic relevance, at least in pediatric ALL; there may be a worse
prognosis for adults with B or T cell lymphomas. Despite the small number of
cases studied, paired sequential analyses suggested that disease progression is
associated with loss of p15/p16 activity in a certain percentage of adult
patients. p15del/p16del and p15met/p16met were also detected in the large panel
of leukemia-lymphoma cell lines studied. In general, the results in cell lines
reproduce the data seen in primary cells with the important difference that the
rates of p15/p16 inactivation are clearly higher in the cultured cells compared
with the freshly explanted cells. Retrovirus- or electroporation-mediated ectopic
gene transfer of p16 wild-type into p16-deficient cell lines led to growth
inhibition, arrest in G1 (without apoptosis) and occasionally to differentiation,
suggesting that the malignant phenotype of p16-/- cell lines can, at least
partially, be reversed by restoring p16 gene expression. A striking inverse
correlation between the absence of p16 (due to deletion) and presence of wild
type retinoblastoma gene was observed in cell lines confirming a common growth
suppressor pathway; no comparable relationship of p16 inactivation with p53 was
detected. Paired analysis of cell lines and corresponding primary cell material
showed that in all instances tested both populations carried the same gene
configuration of p15 and p16. Thus, p15del or p16del did not occur during
establishment of the cell lines or during prolonged culture. It is likely that
p15 or p16 deletions already acquired in vivo provide a dramatic growth advantage
for the immortalization process in vitro, thus increasing the success rate for
cell line establishment which is commonly extremely difficult. In conclusion, the
present review suggests an involvement of the p15 and p16 tumor suppressor genes
in leukemo- and lymphomagenesis. Future studies will determine their exact role
in the development and progression of hematopoietic neoplasms. These genes may
represent interesting targets for new therapeutic strategies.
PMID- 9639411
TI - GM-CSF can improve the cytogenetic response obtained with interferon-alpha
therapy in patients with chronic myelogenous leukemia.
AB - Patients with chronic myelogenous leukemia (CML) who achieve a major cytogenetic
remission when treated with interferon-alpha (IFN-A) have a survival advantage
when compared to patients with no cytogenetic response. We investigated the
effect of combining granulocyte-macrophage colony-stimulating factor (GM-CSF)
with IFN-A in the cytogenetic response of patients with minor responses to IFN-A
alone. CML patients were eligible if they had shown sensitivity to IFN-A as
determined by achievement of a hematologic or cytogenetic response, but failed to
achieve or lost a major cytogenetic response after a minimum of 12 months of
therapy with IFN-A alone. Patients received GM-CSF 30 microg/m2 daily,
subcutaneously and the dose was escalated to 60 microg/m2 if tolerated. IFN-A was
continued at the same dose being received by the patient and escalated when
possible. Fourteen evaluable patients were included, 13 in chronic phase and one
in accelerated phase. The best response prior to GM-CSF was a transient major
cytogenetic response in two patients (14%), minor cytogenetic response in nine
(64%), and complete hematologic response in three (22%). The median time on IFN-A
prior to the start of GM-CSF was 39 months (range 12-72 months). Four patients
achieved a significant cytogenetic response, including two complete (14%) and two
partial (14%) cytogenetic remissions during therapy. One partial cytogenetic
remission converted to complete shortly after therapy was discontinued. Two other
patients had a significant reduction in the percentage of Philadelphia chromosome
positive metaphases. The dose of IFN-A could be escalated in half of the patients
treated. No toxicity could be attributed to the addition of GM-CSF. We conclude
that the addition of GM-CSF to the treatment with IFN-A in CML patients who are
sensitive to IFN-A alone but fail to achieve a major cytogenetic response may be
beneficial in some patients and should be further investigated.
PMID- 9639412
TI - A phase I trial of a single high dose of idarubicin combined with high-dose
cytarabine as induction therapy in relapsed or refractory adult patients with
acute lymphoblastic leukemia.
AB - Relapsed or refractory adult acute lymphoblastic leukemia (ALL) carries a grave
prognosis. The most promising strategy for curing these patients is through re
induction chemotherapy followed by successful allogeneic transplant. We studied a
new high-dose induction regimen in order to improve the outcome for these
patients. Eighteen adult patients with relapsed/refractory ALL were treated on a
phase I study of high-dose cytarabine combined with a single escalating dose of
idarubicin. Five patients had primary refractory disease and 13 were treated in
refractory relapse. Nine patients (50%) had Ph+ ALL. The induction regimen was
cytarabine 3 g/m2/day intravenously days 1-5 and idarubicin as a single
intravenous dose on day 3. G-CSF 5 microg/kg subcutaneously every 12 h was
started on day 7. The initial idarubicin dose was 20 mg/m2 with dose escalations
of 10 mg m2. Cohorts of three patients were treated at each idarubicin dose
level. Unacceptable toxicity was encountered at 50 mg/m2 with one death from
infection and one death from cardiotoxicity in a patient with significant prior
anthracycline exposure. There were no instances of grade 4 non-hematologic
toxicity encountered at idarubicin doses of 20 mg/m2, 30 mg/m2, or 40 mg/m2. The
data suggest a dose-response relationship for increasing doses of idarubicin with
0/3 complete responses (CR) at 20 mg/m2, 1/3 CR at 30 mg/m2, and 7/12 (58%) CR at
idarubicin doses > or = 40 mg/m2. We conclude that concomitant administration of
cytarabine 3 g/m2/day x 5 and high-dose idarubicin at 40 mg/m2 as a single dose
on day 3 can be administered safely to patients with refractory and relapsed ALL.
PMID- 9639413
TI - Polycythemia vera treated with pipobroman as single agent: low incidence of
secondary leukemia in a cohort of patients observed during 20 years (1971-1991).
AB - The 'gold standard' for the treatment of polycythemia vera (PV) is to date
undefined. We performed a retrospective analysis to evaluate the outcome of a
cohort of PV patients treated with pipobroman (PB) at a single institution during
a period of 20 years (November 1971-October 1991). During this period, a total of
366 adult PV patients were diagnosed according to Polycythemia Vera Study Group
(PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and
107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical
characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3
cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white
blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor
neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus
and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1
mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in
females). Thereafter treatment was given according to toxicity and maintenance of
response. All patients were phlebotomized before starting treatment (mean number
of phlebotomies performed: three, range 2-4) and 47 of them received PB when
hematocrit value was already reduced at response levels: therefore, while all
patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%)
patients are evaluable for response to PB. During a median time of 2 months, all
these 152 patients achieved the response; as maintenance, 128/199 (64.3%)
patients were managed with PB alone and 71/199 (35.7%) patients received
phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed
disease-related complications (25 neurological symptoms, 21 thrombotic
complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%)
patients developed acute myelogenous leukemia (AML) after a median time of
treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed
myelofibrosis (median time from treatment 71 months, range 31-182 months) and in
six (3%) patients cancer occurred (median time from treatment 85 months, range 13
118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6%
(95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of
myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years,
respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40
(20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191
months. In conclusion, this retrospective analysis confirms the efficacy and
safety of PB in PV patients and its low leukemogenic role; prospective studies
are needed to evaluate the real impact of PB in the treatment of PV.
PMID- 9639414
TI - Acute lymphoblastic leukemia with maturation--a new entity with clinical
significance.
AB - The diagnosis of 'ALL with maturation' (ALLm) is proposed. One hundred and one
patients with untreated ALL were entered into this study. The diagnosis of ALLm
was made when more than 20% of all nucleated elements in the bone marrow showed
maturation beyond prolymphocytes by light microscopic examination. The mature
appearing leukemic cells showed the same immunophenotype to remaining
lymphoblasts. The number of ALLm cases was 19 (18.8%). The mean age at
presentation of ALLm was 29 +/- 18, older than that of 18 +/- 16 of the remaining
typical ALL (ALLt) (P = 0.015). Remission was induced with daunorubicin,
vincristine, prednisone and L-asparaginase. Only two of 19 ALLm patients achieved
CR after 4 weeks induction chemotherapy. In contrast, 57 of 82 (69.5%) ALLt
patients achieved CR after the same induction chemotherapy. There was no
significant difference in immunophenotype of ALLm compared with ALLt. Labeling
index of DNA topoisomerase IIalpha (TopoLI) was studied by immunohistochemistry.
Initial TopoLI of ALLm (221 +/- 147) was much lower than that of ALLt (609 +/-
262, P = 0.005). Furthermore, the remaining leukemic cells after chemotherapy
were not labeled with anti-DNA topoisomerase IIalpha. The P53 protein was
expressed in nine of 18 ALLm cases (50.0%) and P-glycoprotein was not expressed
in ALLm cases. Twelve of 19 ALLm cases were studied for carrying bcr/abl fusion
by karyotyping and/or fluorescent in situ hybridization. Only two cases revealed
bcr/abl fusion. In conclusion, ALLm is a separate entity of ALL which has a very
poor clinical course and is independent of other prognostic factors. The
morphologically mature leukemic cells are in resting GO phase.
PMID- 9639415
TI - CD34+/CD36- cells from myelodysplasia patients have a limited capacity to
proliferate but can differentiate in response to Epo and MGF stimulation.
AB - Myelodysplasia (MDS) is mostly characterized by a normal or increased number of
normoblasts in the bone marrow and an impaired in vitro colony formation. In the
present study we analyzed whether this might be due to a disconnection between
proliferation and differentiation. CD34+/CD36- sorted bone marrow cells of 18 MDS
patients were cultured in a clonogenic and suspension culture assay in the
presence of erythropoietin (Epo) and mast cell growth factor (MGF). Burst-forming
units erythroid (BFU-E, 75 +/- 88/10(4) CD34+ cells, X +/- s.d.) and colony
forming units E (CFU-E) were observed in eight of the 13 cases (62%) with
refractory anemia with or without ring sideroblasts (RA and RARS) and one of the
five cases with RA with excess of blasts or in transformation (RAEB and RAEB-T).
Suspension cultures with CD34+/CD36- sorted cells with Epo plus MGF demonstrated
an 8.9 +/- 6.5-fold expansion after 7 days in cases with >10 BFU-E/10(4)
CD34+/CD36- cells while cases with <10 BFU-E/10(4) CD34+/CD36- cells demonstrated
1.0 +/- 0.8-fold expansion especially in cases with RAEB/RAEB-T. FACS and
morphology analysis after 7 days of suspension culture demonstrated partial
differentiation along the erythroid lineage in cases with RA/RARS (75%) and
RAEB/RAEB-T (66%) reflected by the presence of erythroblasts and normoblasts with
variable expression of CD34, CD36 and Glycophorin A. In cases with erythroid
colony formation 69 +/- 24% of the cells were CD34-/CD36+ and in cases with <10
BFU-E/10(4) CD34+ cells 18 +/- 16% of cells were CD34-/CD36+. Iron staining
showed the presence of ring sideroblasts in two cases with RARS indicating that
the cells originate from the abnormal erythroid clone. Finally, it was shown that
cases with an impaired proliferative response demonstrate an enhanced binding of
Annexin-V on CD34+ cells during the first days of the cell suspension culture
phase. These results suggest that a defect in the proliferative response is most
pronouncedly expressed in MDS whereas a subpopulation of cells retain the
capacity to differentiate between transition to a terminated stage.
PMID- 9639416
TI - RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10
year follow-up.
AB - The molecular mechanisms underlying the development and evolution of
myelodysplastic syndrome (MDS) are largely unknown. The increasing number of
blast cells in the bone marrow correlate with poor prognosis and risk of
developing acute leukemia. Such progression is frequently associated with
increasing chromosomal abnormalities and genetic mutations. A cohort of 75 MDS
patients were investigated for RAS, FMS and p53 mutations, and these molecular
findings were related to cytogenetics, clinical status, transformation to acute
leukemia, prognostic scores and survival. A mutation incidence of 57% (43/75) was
found, with 48% (36/75) RAS mutations, 12% (9/75) FMS mutations and 8% (4/50) p53
mutations. The mutation status for RAS and FMS was related to MDS subgroup,
increasing with poor-risk disease. The highest incidence was in the chronic
myelomonocytic leukemia (CMML) subgroup. The most frequent RAS mutations were of
codon 12 and a predominance of FMS codon 969 mutations was observed. A
statistically significant increased frequency of transformation to AML was
observed in MDS patients harboring RAS or FMS mutations (P < 0.02). Patients with
oncogene mutations had a significantly poorer survival compared with those
without mutations at 2 years and at the end of the period of follow-up (P <
0.02). Multivariate analysis including mutation, age, gender, diagnosis (FAB),
cytogenetics and International score shows that the International score and
mutation and age is the best predictive model of a poor outcome, (P < 0.0001).
When the analysis was undertaken without the International score, mutation and
gender was the best predictor of poor survival (P = 0.005). This study shows that
oncogene mutation, indicative of genetic instability, is associated with disease
progression and poor survival in MDS.
PMID- 9639417
TI - Cyclin A1 is predominantly expressed in hematological malignancies with myeloid
differentiation.
AB - Cyclin A is a cell cycle regulatory protein that functions in mitotic and S phase
control in mammalian cells. However, in contrast to other G1 phase regulatory
proteins, such as cyclin D, retinoblastoma protein and p16INK4A, cyclin A seems
not to be commonly involved in tumorigenesis. Recently, a second human cyclin A-
cyclin A1--has been identified. In contrast to cyclin A which is expressed
throughout embryonic development and in adult tissue, the expression of cyclin A1
has been reported to be restricted to embryonic and germ line cells. We have
confirmed the absence of cyclin A1 mRNA from normal peripheral blood leukocytes
of seven healthy donors by single step reverse transcriptase-polymerase chain
reaction (RT-PCR). Furthermore, we have examined the expression of cyclin A1 mRNA
in 173 peripheral blood samples of 162 patients with various hematological
malignancies. Cyclin A1 mRNA was detectable in 11 of 11 patients with acute
myeloid leukemia, three of three patients with acute biphenotypic leukemia, eight
of eight patients with myelodysplastic syndrome, 59 of 69 patients with chronic
myelogenous leukemia (CML) at diagnosis, 13 of 15 patients with CML in blastic
transformation, 10 of 18 patients with chronic lymphocytic leukemia, two of nine
patients with essential thrombocythemia, and only two of 10 patients with acute
lymphoblastic leukemia (ALL) with both cyclin A1 RT-PCR positive ALL leukemias
being undifferentiated relapses. In addition, cyclin A1 mRNA was found in one of
six leukapheresis products, harvested from individuals without hematological
disorders. Taken together, cyclin A1 is expressed in the majority of myeloid and
undifferentiated hematological malignancies as well as in normal hematopoietic
progenitor cells. We conclude that cyclin A1, a protein potentially involved in
G1/S phase progression of immature cells, might be necessary for proliferation of
early hematopoietic progenitor cells and their leukemic counterparts being
blocked at that stage of differentiation.
PMID- 9639418
TI - Increased expression of the differentiation-defective granulocyte colony
stimulating factor receptor mRNA isoform in acute myelogenous leukemia.
AB - Granulocyte colony-stimulating factor (G-CSF) critically affects all stages of
granulopoiesis by activating a signaling cascade initiated by dimerization of its
receptor (G-CSFR). Five human G-CSFR isoforms have been identified (classes I-V).
A quantitative polymerase chain reaction (Q-PCR) technique was used to examine
the expression of these five isoforms in normal and leukemic myeloid cells. We
demonstrated that neutrophils expressed predominantly the class I isoform and low
levels of class IV isoform (IV/I = 0.037 +/- 0.005). No expression of the class
II, class III, or class V isoform was detected. In contrast, all AML cell lines
and acute myelogenous leukemia (AML) patient samples expressed increased relative
amounts of the class IV isoform (IV/I = 0.047-0.350). When compared to normal
immature myeloid cells, as represented by the CD34+ fraction of adult bone marrow
(ABM) cells, three of eight AML cell lines and three of six AML patient samples
expressed significantly increased levels of the class IV isoform relative to
class I. This suggests that the increase in the relative expression of the class
IV isoform seen in a considerable portion of AML cell samples is related to their
leukemic phenotype. Given the inability of the class IV G-CSFR to drive myeloid
maturation, the relative increase in class IV expression in AML cells may
contribute to their aberrant response to G-CSF.
PMID- 9639419
TI - Recombinant human megakaryocyte growth and development factor (MGDF) increases
the numbers of megakaryocyte progenitor cells to normal values in long-term bone
marrow cultures of patients with AML in first remission.
AB - The megakaryopoietic potential in the bone marrow (BM) of patients in first
remission after treatment for acute myelogenous leukaemia (AML) was investigated
using long-term bone marrow cultures (LTC) stimulated with megakaryocyte growth
and development factor (MGDF). The baseline number of megakaryocyte colony
forming cells (Meg-CFC) was very low. However, there was a 10 to 100-fold
increase of Meg-CFC in cultures treated with 10 ng/ml MGDF with mean numbers
within the normal range for the first 4 weeks of culture with a 24-fold increase
in their cumulative numbers. Similarly, a 12-fold increase in the numbers of
megakaryocytes (MKs) was found by CD61 immunostaining. These effects were lost at
the dose of 100 ng/ml. In contrast, the cumulative mean numbers of Meg-CFC in the
control cultures from normal bone marrow (NBM) were not significantly different
from those in cultures treated with 10 or 100 ng/ml MGDF. These results
demonstrate that MGDF stimulates megakaryocytopoiesis in patients with AML in
first remission, restoring the Meg-CFC compartment to normal values, a result
with potential clinical implications for their treatment with autologous
transplantation.
PMID- 9639420
TI - The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in
vitro cytotoxicity and intracellular content of daunorubicin in childhood acute
lymphoblastic leukemia.
AB - Resistance to anthracyclines is related to a poor prognosis in childhood acute
lymphoblastic leukemia (ALL). Resistance to this class of drugs may (partly) be
reversed by modulating agents, as has been demonstrated in a variety of cell
lines. However, it is unknown which modulators may be of clinical benefit in
childhood ALL. Therefore, we studied the modulating effect of PSC 833,
cyclosporin A (CsA), verapamil (Vp) and genistein on daunorubicin (DNR)
cytotoxicity, accumulation and retention in childhood ALL cells. DNR cytotoxicity
was determined using the MTT assay; DNR accumulation, DNR retention and the
expression of P-glycoprotein (P-gp), multidrug resistance-associated protein
(MRP) and major vault protein/lung resistance protein (LRP) were determined by
flow cytometry. In the majority of samples PSC 833 (19/26), CsA (22/26) and Vp
(15/18) sensitized the cells to DNR whereas genistein made 25 out of 26 samples
more resistant to DNR. The sensitizing effect on the cytotoxicity of DNR was
median 1.2-fold using 2 microM PSC 833 (P = 0.025), 1.5-fold using 4 microM CsA
(P = 0.003) and 1.6-fold using 6 microM Vp (P = 0.012) whereas the adverse effect
of 25 microM genistein was median 1.8-fold (P < 0.0001). No relationship was
found between the sensitizing effect of PSC 833, CsA or Vp and the degree of DNR
resistance. In contrast, the adverse effect of genistein was largest in DNR
sensitive samples (P = 0.003). The effect of each modulator on the cytotoxicity
of DNR did not differ between initial and relapse ALL samples although the latter
were median 1.4-fold more resistant to DNR (P = 0.005). Modulation of DNR
cytotoxicity was not correlated with changes in the accumulated and retained
intracellular DNR content or with the expression of P-gp, MRP and LRP. Besides
genistein, PSC 833, CsA and Vp incidentally made ALL cells more resistant to DNR.
CsA stimulated the leukemic cell survival in seven out of 26 samples, a
phenomenon that was not related to the degree of DNR resistance. In conclusion,
PSC 833, CsA and Vp but not genistein may be used to sensitize cells to DNR in
childhood ALL. The data also indicate that not all patients may have a
therapeutic benefit from these modulators. Therefore, an in vitro culture assay
may be necessary to screen for patients who may benefit by a modulator in their
therapy.
PMID- 9639421
TI - Multiplication and death-type of leukemia cell lines exposed to very long-chain
polyunsaturated fatty acids.
AB - Polyunsaturated fatty acids (PUFA) may reduce cell multiplication in cultures of
normal, as well as transformed, white blood cells. We assessed the sensitivity of
14 different leukemia cell lines to PUFA by measuring cell number after 3 days of
incubation. Ten of the examined cell lines were sensitive to 30, 60 and/or 120
microM of arachidonic, eicosapentaenoic and docosahexaenoic acid, whereas four
cell lines were resistant. The sensitivity to PUFA was not associated with any
particular cell lineage, clinical origin or specific mRNA pattern of bcl-2 and c
myc. Effects on cell viability were assessed by studying cell membrane integrity,
DNA fragmentation and cell morphology. The sensitive cell lines Raji and Ramos
died by necrosis and apoptosis, respectively, during incubation with
eicosapentaenoic acid, whereas the viability of the resistant U-698 cell line was
unaffected. The effects of EPA on Raji cells, was counteracted by vitamin E,
indicating that lipid peroxidation was involved. However, apoptosis induced by
eicosapentaenoic acid in Ramos cells, was unaffected by vitamin E, as well as
eicosanoid synthesis inhibitors. In conclusion, our results indicate that a
majority of leukemia cell lines are sensitive to PUFA. This sensitivity may be
caused by induction of apoptosis or necrosis by very long-chain polyunsaturated
fatty acids.
PMID- 9639422
TI - Arginine butyrate downregulates p210 bcr-abl expression and induces apoptosis in
chronic myelogenous leukemia cells.
AB - Downregulation of bcr-abl expression in the chronic myelogenous leukemia cell
line K562 using antisense oligonucleotides has been shown to enhance the
sensitivity of the cells to apoptotic stimuli, suggesting that p210 bcr-abl, like
bcl-2 functions as an anti-apoptosis factor (McGahon A et al, Blood 1994, 83:
1179). In these experiments, the inhibition of p210 bcr-abl expression alone was
not sufficient to induce apoptosis. We demonstrated that exposure to low doses
(0.5 mM) of a butyric acid analog, arginine butyrate, was capable of inducing
apoptosis in selected leukemia cell lines, including K562 cells, and in fresh
leukemia cells from patients with chronic myelogenous leukemia. To further
explore the mechanisms of this effect, we examined expression of p210 bcr-abl
after butyrate exposure and found a dose-related inhibition of p210 bcr-abl
protein without concordant change in other phosphoproteins, including the JAK-1
kinase. Further analysis revealed that the inhibition of bcr-abl expression
occurs due to transcriptional regulation of the bcr-abl gene by arginine
butyrate. These results suggest that arginine butyrate and other butyrate analogs
alone or in combination may be useful in the therapy of patients with chronic
myelogenous leukemia or bcr-abl expressing acute leukemias.
PMID- 9639423
TI - Hypermethylation of p15/ink4b/MTS2 gene is differentially implicated among non
Hodgkin's lymphomas.
AB - P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the
p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15
genes, however, mutations in the coding sequence of the p15 gene have not been
found in the majority of tumors analyzed, including non-Hodgkin's lymphomas.
Abnormal methylation of the promoter region of p15 has been recently described as
an alternative mechanism of inactivation of this gene. We analyzed 72 non
Hodgkin's lymphomas (NHL) for methylation at p15 exon 1 by PCR and Southern blot
techniques using methylation-sensitive restriction enzymes. Abnormal methylation
was found in eight cases (11%), most of them (three MALT, one anaplastic T cell
lymphoma, one Burkitt and one follicular lymphoma) showing hypermethylation in
the p16 gene also. In contrast, two pleomorphic T cell NHL showed a selective
methylation at p15 gene, while the p16 gene remained unmethylated. The results
show that methylation at the p15 gene is frequently associated with p16
methylation in NHL, and suggest that selective methylation of p15, although
uncommon, could be a specific alteration implicated in T cell NHL.
PMID- 9639424
TI - CD34+, kit+, rhodamine123(low) phenotype identifies a marrow cell population
highly enriched for human hematopoietic stem cells.
AB - We hypothesized that human hematopoietic cells displaying a CD34+, kit-,
rhodamine123(low) phenotype would be highly enriched for cells with stem-like
properties. To test this hypothesis, we employed fluorescence activated cell
sorting (FACS) to isolate cells with this phenotype from normal light density
marrow mononuclear cells (MNC). CD34+, kit+, rhodamine123(low) cells comprised
from 0.05-0.01% of the total MNC population. They were small, had scant
cytoplasm, and contained nuclei with dense, hyperchromatic chromatin and
inconspicuous nucleoli. Additional immunophenotyping revealed that these cells
were CD33-, CD38-, CD20-, and glycophorin A-. When plated in semisolid cultures
containing optimal concentrations of IL-3, GM-CSF, KL, EPO, IL-6, and IL-1 these
cells did not form colonies. However, when cultured over irradiated stromal
cells, cobblestone areas were observed to form after 3 weeks, and harvested cells
were able to initiate long-term cultures. To further demonstrate that these cells
were indeed stem like, we also tested their ability to engraft and mature in
immunocompromised (SCID) mice. Irradiated (400 cGy) SCID mice were transplanted
with 2 x 10(3) candidate stem cells which were then injected with recombinant
human growth factors every other day. Two months post-transplant the animals were
sacrificed. PCR and FACS analysis of marrow and spleen cell samples revealed the
presence of cells expressing human CD45 consistent with engraftment of human stem
cells and the establishment of murine-human chimerism. Moreover, MNC isolated
from transplanted mice formed unambiguously human BFU-E, CFU-GM and B cell
colonies when stimulated with the appropriate growth factors. Accordingly, we
have identified a relatively rapid and simple mechanism for isolating primitive
human hematopoietic cells with stem cell-like properties. We anticipate that this
strategy will be useful for experimental and therapeutic applications that
require human stem cells in quantity.
PMID- 9639425
TI - Stroma-conditioned medium and sufficient prestimulation improve fibronectin
fragment-mediated retroviral gene transfer into human primitive mobilized
peripheral blood stem cells through effects on their recovery and transduction
efficiency.
AB - Mobilized peripheral blood stem cells (PBSC) are an attractive vehicle for cancer
gene therapy. However these stem cells may have a reduced proliferative capacity
due to previous cytotoxic chemotherapy treatment of the patient. In addition,
primitive hematopoietic stem cells (HSC) from mobilized peripheral blood are
almost exclusively quiescent, which makes it hard to induce proliferation in
vitro and thus to improve stable transduction of introduced genes into a
sufficiently large number of primitive stem cells. In this study CD34-selected
mobilized PBSC from lymphoma and myeloma patients were used as target cells for
retroviral-mediated gene transfer using a clinically relevant cell- and serum
free supernatant transduction protocol. We have investigated various parameters
that may contribute to an improvement of the poor transduction efficiency of the
primitive HSC, including prestimulation time, the use of the carboxy-terminal
fibronectin fragment CH-296, as well as stromal cell line conditioned media.
Retroviral supernatant transduction in combination with CH-296 increased
significantly the gene transfer efficiency as compared to supernatant alone and
made the use of polycations redundant. Gene transfer of primitive HSC
(cobblestone area forming cell (CAFC) week 6) was specifically improved when this
procedure was preceded by a 5-day pre-culture period as compared to a 2-day
transduction procedure. However, irrespective of the numerical recovery, the CAFC
week 6 after retroviral transduction produced less long-term culture colony
forming cells, suggesting a loss of individual stem cell quality. The addition of
stroma-conditioned media during the pre-culture period did not affect the
individual CAFC quality or transduction efficiency, but increased greatly the
recovery of the total number of transduced and untransduced HSC leading to larger
grafts containing higher numbers of transduced stem cells.
PMID- 9639426
TI - Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different
diseases.
AB - We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients
with abnormal karyotypes. Most karyotypes were complex with numerical and
structural abnormalities but the analysis of chromosomal abnormalities allowed
identification of two cytogenetic patterns depending on the chromosome number: a
first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and
19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near
tetraploid karyotypes. Structural abnormalities were present in all but five
hyperdiploid karyotypes, and frequently involved lymphoid breakpoints:
immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases).
Numerous other structural aberrations were detected; the most frequent involved
chromosome 1 and chromosome 13. Structural abnormalities were significantly more
frequent in the second hypodiploid group. When analyzing the results obtained in
the 60 patients studied at the time of diagnosis, a prognostic correlation was
found between the cytogenetic pattern and overall survival: hyperdiploid patients
had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid
group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that
MM could correspond to two closely related diseases.
PMID- 9639427
TI - Amplification of the TCL1 flanking region at 14q32.1 with no TCL1 gene
transcription in a patient with peripheral T cell lymphoma.
AB - Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma
(PTL) have not been well defined, except for those in adult T cell
leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome
band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We
studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in
tumor tissues from 20 patients with PTL including three with 14q32 translocations
by two color fluorescent in situ hybridization (FISH) using two cosmid probes
flanking the TCL1 gene. The two cosmid signals were separated in none of them,
but much increased in number in one tumor without 14q32 translocation, indicating
that the TCL1 genomic region was amplified in this tumor. Reverse transcription
polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript
in the tumor. These findings suggest that an oncogene other than TCL1 may be
located in 14q32.1, and its amplification may be involved in the neoplastic
process of PTL.
PMID- 9639428
TI - Abnormalities of the short arm of chromosome 12 in T cell prolymphocytic
leukemia.
AB - Abnormalities of the short arm of chromosome 12 are nonrandom events in T cell
prolymphocytic leukemia (T-PLL). Fluorescence in situ hybridization (FISH)
studies were performed in three patients with T-PLL and one patient with T cell
peripheral lymphoma and rearrangement of 12p. Whereas the rearrangements of 12p
were different in the four patients, a breakpoint centromeric to the ETV6 gene
was present in the three T-PLL patients. In addition, loss of heterozygosity for
a chromosomal segment telomeric to ETV6 with loss of the RAD52 locus was also
shown by FISH studies. In contrast, the breakpoint was telomeric to ETV6 in the
patient with peripheral lymphoma.
PMID- 9639429
TI - Panhandle PCR: a technical advance to amplify MLL genomic translocation
breakpoints.
AB - Translocations involving a breakpoint cluster region of the MLL gene at
chromosome band 11q23 are the most common molecular abnormalities in acute
leukemias of infants and acute leukemias related to chemotherapy with DNA
topoisomerase II inhibitors. Molecular cloning of MLL genomic breakpoints by PCR
has previously been difficult because MLL has many translocation partners and
several breakpoints involve unknown partner genes. We review a new approach to
MLL genomic breakpoint cloning called panhandle PCR. By adding an oligonucleotide
sequence to the unknown 3' partner gene that is complementary to a known 5' MLL
sequence, we have been able to generate a genomic template with an intrastrand
loop for PCR schematically shaped like a pan with a handle. The intrastrand loop
contains the translocation breakpoint and unknown partner DNA, while the handle
contains the known 5' sequence from MLL and a complement to that sequence.
Primers both derived from MLL are used to amplify the breakpoint by panhandle
PCR. Panhandle PCR offers the advantage of having specificity for the strand of
interest at both primer annealing sites without requiring specific primers for
the many partner genes of MLL. Panhandle PCR is a straightforward method that
represents a technical advance in MLL genomic breakpoint cloning.
PMID- 9639430
TI - Examination of a role for idiotypy in the disease remission of a long-term
survivor of adult T cell leukemia treated with anti-Tac antibody.
AB - The alpha chain of the interleukin 2 receptor (IL2R alpha; Tac) was targeted in
clinical trials with adult T cell leukemia using murine anti-Tac antibody. Of 19
patients, a single individual achieved a durable complete remission. The
mechanism of this action by murine anti-Tac has not been defined. We examined the
hypothesis that the maintenance of the long-term response after treatment might
be related to induction of a network of anti-idiotypic antibodies, as proposed in
other tumor settings. In contrast to anti-Tac non-responders, the patient was
found to have produced a human anti-mouse antibody (HAMA) response, and
specifically an anti-idiotypic (Ab2) response, that was readily detectable by
standard assays 4 years after treatment. Using phage display antibody libraries,
this response was shown to be monoclonal, consisting of a single IgG1,kappa
antibody of moderate affinity. No evidence was found for anti-anti-idiotypic
(Ab3) antibodies with reactivity for sTac, which might alternatively have
maintained an autogenic human anti-Tac antibody response. An area of limited
homology was noted between the Ab2 antibody and the IL2R in the domain of IL2
binding, but no binding of Ab2 to IL2 could be shown that might have reduced
endogenous ligand (IL2) concentrations. Similarly, no anti-anti-idiotypic (T3) T
cell response was detected. Thus, we are unable to confirm features of idiotypy
that could suggest a role in maintaining an anti-tumor response by anti-Tac
antibody therapy.
PMID- 9639431
TI - Prolonged molecular remission after PML/RAR alpha-positive autologous peripheral
blood stem cell transplantation in acute promyelocytic leukemia: is relevant
pretransplant minimal residual disease in the graft?
AB - The contribution of residual malignant cells contaminating the autologous graft
with the occurrence of post-transplant relapse in acute myeloid leukemia (AML) is
still unclear. The presence of a specific molecular marker (the PML/RAR alpha
rearrangement) in acute promyelocytic leukemia (APL) offers the opportunity to
investigate better the pathogenesis of disease recurrence after transplant. We
report an APL patient who received high-dose chemotherapy and peripheral blood
stem cell (PBSC) autograft in second hematologic remission. Two leukaphereses
that tested PML/RAR alpha positive by RT-PCR were obtained during the post
reinduction hematopoietic recovery, while the patient also tested PCR positive in
the BM, and was reinfused after myeloablative chemotherapy (BUCY4), when the
patient had spontaneously converted to PCR negative in the marrow. At present, he
remains in continuous molecular and hematologic remission 22 months after PBSC
transplantation. This is the second report of an APL patient who was transplanted
in molecular remission with a PML/RAR alpha-positive PBSC autograft. As in the
previous report, the prolonged clinical and molecular remission experienced post
transplant suggests that autologous PBSC infusion is still worthy of
consideration for patients with APL in spite of the detection of PML/RAR alpha
positive cells in the PBSC collections. Possible underlying mechanisms and the
potential role of molecular monitoring of the graft, as well as the host, before
and after transplant, in patients with APL undergoing autologous HSCT are also
discussed.
PMID- 9639432
TI - Impact of TEL/AML1-positive patients on age distribution of childhood acute
lymphoblastic leukemia in Czech Republic. Pediatric Hematology Working Group in
Czech Republic.
PMID- 9639433
TI - Peripheral blood progenitor cells mobilized early at diagnosis in patients with
chronic myelogenous leukemia contain very low amounts of BCR-ABL transcripts.
PMID- 9639434
TI - Cytogenetic response induced by interferon alpha in the myeloproliferative
disorder with eosinophilia, T cell lymphoma and the chromosomal translocation
t(8;13)(p11;q12)
PMID- 9639435
TI - Susceptibility of the adult T cell leukemia (ATL) cell lines to HHV-6B.
PMID- 9639436
TI - Identification of integrated human herpesvirus 6 DNA in early pre-B cell acute
lymphoblastic leukemia.
PMID- 9639437
TI - Fulminant hepatosplenic B cell lymphoma in a young patient with HCV-chronic
hepatitis.
PMID- 9639438
TI - Late relapse in BCR/ABL-positive patients after non-intensive chemotherapy.
PMID- 9639439
TI - Pupil involvement in patients with diabetes-associated oculomotor nerve palsy.
AB - OBJECTIVE: To derive a reliable estimate of the frequency of pupil involvement in
patients with diabetes-associated oculomotor nerve palsy. PATIENTS AND METHODS:
In this prospective study, standardized enrollment criteria were employed to
identify 26 consecutive patients with diabetes-associated oculomotor nerve palsy
who were evaluated in a referral-based, outpatient neuro-ophthalmology practice.
A pupil ruler accurate to within 0.5 mm was used to measure pupil diameters using
a standardized procedure. The degree of anisocoria, if present, was recorded at
each office visit until the ophthalmoplegia had resolved. Descriptive statistics
were used to identify the frequency and characteristics of pupil involvement.
RESULTS: Internal ophthalmoplegia occurred in 10 (38%) of 26 patients. The size
of the anisocoria was 1 mm or less in most patients. None of the patients had a
fully dilated unreactive pupil. CONCLUSIONS: Pupil involvement in patients with
diabetes-associated oculomotor nerve palsy occurs more often than has been
previously recognized, although the degree of anisocoria in any 1 patient is
usually only 1 mm or less. Some characteristics of the internal ophthalmoplegia
may help to distinguish diabetic ophthalmoplegia from injury of the oculomotor
nerve caused by aneurysmal compression.
PMID- 9639440
TI - Angle-closure glaucoma associated with occult annular ciliary body detachment.
AB - OBJECTIVE: To evaluate the role of annular ciliary body detachment in the
development of postoperative angle-closure glaucoma. DESIGN: Case series.
SETTING: Tertiary care glaucoma referral center. METHODS: High-resolution,
anterior segment ultrasound biomicroscopy, ophthalmoscopy, and B-scan
ultrasonography were performed on 6 eyes of 6 patients with a clinical diagnosis
of postoperative malignant glaucoma. RESULTS: Each eye had an elevated
intraocular pressure, a shallow anterior chamber, 1 or more patent iridectomies,
and no ophthalmoscopic or B-scan ultrasound evidence of serous or hemorrhagic
ciliochoroidal detachment. Ultrasound biomicroscopy revealed annular ciliary body
detachment in each eye. In 4 eyes, observation with topical medical treatment was
associated with deepening of the anterior chamber, reduced intraocular pressure,
and resolution of the detachment. Drainage of the supraciliary fluid was
performed in 2 eyes. CONCLUSION: Occult, annular, serous detachment of the
ciliary body may cause postoperative angle-closure glaucoma. This entity is
clinically indistinguishable from malignant glaucoma. Ultrasound biomicroscopy
facilitates the diagnosis.
PMID- 9639441
TI - Transforming growth factor beta2 in the vitreous in proliferative diabetic
retinopathy.
AB - OBJECTIVE: To evaluate the hypothesis that transforming growth factor beta2 (TGF
beta2) is involved in the cause of proliferative diabetic retinopathy (PDR).
METHODS: We assayed TGF-beta2 levels in the vitreous of patients with PDR and
other vitreoretinal disorders. Forty-nine vitreous specimens were obtained from
eyes of patients with PDR undergoing vitrectomy, and 19 vitreous specimens from
nondiabetic subjects served as controls. We assessed TGF-beta2 levels using an
enzyme-linked immunosorbent assay. Both mature and total TGF-beta2 levels were
quantified. RESULTS: The mean (+/- SD) total levels of TGF-beta2 were 2634 (+/-
1652) pg/mL in the patients with PDR and 1305 (+/- 972) pg/mL in controls. The
mean (+/- SD) levels of mature TGF-beta2 were 244 (+/- 316) pg/mL in patients
with PDR and 79 (+/- 81) pg/mL in controls. Total and mature TGF-beta2 levels
were significantly greater in patients with PDR (total TGF-beta2, P <.001; mature
TGF-beta2, P <.01). Mature TGF-beta2 levels were higher in the vitreous of
patients who had severe fibrous proliferation. CONCLUSION: The results indicate
increased levels of both total and mature TGF-beta2 in the vitreous of patients
with PDR, suggesting that TGF-beta2 plays an important role in the pathogenesis
of PDR.
PMID- 9639442
TI - Histopathologic and ultrastructural findings of surgically excised choroidal
neovascularization. Submacular Surgery Trials Research Group.
AB - OBJECTIVE: To study the histologic and ultrastructural features of surgically
excised choroidal neovascularization (CNV) from patients who had undergone
submacular surgery. MATERIALS AND METHODS: Voluntarily submitted surgically
excised CNV specimens from a subset of specimens obtained by the Submacular
Surgery Trials Research Group between January 1, 1994, and December 31, 1996,
were available for this study. The specimens were routinely processed for
transmission electron microscopic examination. The largest horizontal and
vertical dimensions, cellular and extracellular constituents, and relationship of
the CNV to the neurosensory retina and retinal pigment epithelium (RPE) were
recorded. RESULTS: Seventy-eight surgical specimens were obtained from 160
patients treated surgically in Submacular Surgery Trials centers. Sixty-one (78%)
were from patients with age-related macular degeneration (ARMD) and 17 (22%) were
from patients with ocular histoplasmosis syndrome or idiopathic causes (hereafter
referred to as the non-ARMD group). The histologic diagnosis was fibrovascular
tissue, fibrocellular tissue, or hemorrhage in all cases. Vascular endothelium
and RPE were the most common constituents of the CNV. Basal laminar deposit was
only present in CNV from patients with ARMD. Age-related macular degeneration
specimens were larger (mean +/- SD, 2042 [+/- 1175] x 320 [+/- 185] microm vs
1498 [+/- 792] x 227 [+/- 166] microm) and were more likely to have a sub-RPE
(beneath the RPE) component than non-ARMD specimens. CONCLUSIONS: All evaluated
surgically excised CNV specimens in this study from patients enrolled in the
Submacular Surgery Trials consisted of fibrovascular tissue, fibrocellular
tissue, or hemorrhage. Surgically excised CNV associated with ARMD in this series
was larger and often was located beneath the RPE compared with non-ARMD CNV,
although fewer than half of all the specimens could be oriented by topographic
relationship to the RPE.
PMID- 9639443
TI - Long-term follow-up of iatrogenic phototoxicity.
AB - OBJECTIVE: To evaluate the outcomes of a group of patients who suffered
iatrogenic phototoxic injury. METHODS: The medical records of 24 patients (24
eyes) with iatrogenic phototoxicity from 3 medical centers were reviewed. We
report the findings from long-term follow-up of these patients with particular
attention to visual outcome, type and duration of procedure, and location of the
phototoxic lesion. RESULTS: Phototoxic injury occurred after anterior segment
surgery in 20 eyes and after vitrectomy in 4 eyes. The mean duration of surgery
was 109 minutes; there was no statistically significant difference in duration
between the anterior segment procedures and the vitrectomies. Mean final visual
acuity was 20/40 for all cases (range, 20/15 to counting fingers) and 20/25 for
all anterior segment cases. In vitrectomized eyes, the mean final visual acuity
was 20/900. Phototoxic lesions tended to spare the fovea after anterior segment
surgery and involve the foveal center after vitrectomy. CONCLUSIONS: In general,
patients who suffer phototoxicity do well, and the prognosis is good for
extrafoveal lesions. Foveal injury, which often occurs with vitrectomy, usually
leads to a worse visual outcome. The development of choroidal neovascularization
may have an effect on the ultimate visual outcome as well.
PMID- 9639444
TI - Effects of fenretinide (4-HPR) on dark adaptation.
AB - OBJECTIVES: To assess the alterations in dark adaptation induced by low (200
mg/d) doses of fenretinide (4-HPR), to assess whether these effects were
cumulative and whether they were reversible, and to attempt to elucidate the
mechanism underlying the changes in night vision. DESIGN: Case series. SETTING:
Outpatient eye clinic. PATIENTS: Twenty-two women enrolled in a breast cancer
chemoprevention trial, and 18 normal control subjects. INTERVENTION: Measurements
of absolute luminance thresholds during dark adaptation. MAIN OUTCOME MEASURES:
Parameters of an exponential model of the dark-adaptation function before,
during, and after administration of fenretinide. RESULTS: The most conspicuous
effect of fenretinide on dark adaptation was a significant delay in the timing of
the rod-cone break (P<.001). A minimal elevation of the final cone threshold was
also observed. These effects were reversible after fenretinide therapy was
discontinued and did not seem to be cumulative. An inverse relationship between
delay of the rod-cone break and plasma retinol concentration was found.
CONCLUSION: The dose of fenretinide used in this study produced clearly
measurable, but not severe, changes in night vision, which were rarely
symptomatic.
PMID- 9639445
TI - Vertical location of the corneal light reflex in strabismus photography.
AB - OBJECTIVE: To improve the clinical documentation of strabismus by mathematically
predicting and clinically verifying the location of a fixation target that
produces a vertically centered corneal light reflex (first Purkinje image) in
clinical photographs of the eye using a standard photographic flash unit.
MATERIALS AND METHODS: Mathematical modeling of the corneal light reflex during
clinical photography was based on the schematic eye. Clinical photographs were
taken using a range of fixation targets located between the center of the camera
lens and the center of the flash. Image quality was also assessed subjectively.
RESULTS: Optimum vertical centration of the corneal light reflex was predicted
and produced when the fixation target was located one fifth of the distance from
the center of the flash to the center of the camera lens. Placement of the flash
below, rather than above, the camera lens provided more uniform illumination of
the patient's eyes and face. Decreasing the distance between the camera lens and
the flash minimized the severity of these artifacts. CONCLUSIONS: A poorly
positioned corneal light reflex makes it difficult to identify the fixing eye in
photographs of patients with strabismus, especially when vertical strabismus is
present. Adoption of the aforementioned protocol will reproduce the appearance of
coaxially viewed corneal light reflexes and provide much-needed standardization
for strabismus case presentation.
PMID- 9639446
TI - Development of tearing in preterm and term neonates.
AB - BACKGROUND: Although term and preterm infants have the capacity to secrete tears,
the relative contribution of basal and reflex secretion of tears has not been
previously assessed together in a prospective study. This information potentially
has practical clinical importance. OBJECTIVES: To measure basal and reflex tear
secretion in preterm (30-37 weeks after conception) and term (38-42 weeks)
newborns and to determine the developmental pattern of tear production. METHODS:
Tear secretion was evaluated by applying Schirmer tear test strips to the
inferior fornix for 5 minutes before (reflex plus basal secretion) and after
(basal secretion) applying a topical anesthetic agent. RESULTS: Seventy infants
(36 preterm and 34 term) were tested. Mean (+/- SD) basal tear secretion was 6.2
(+/- 4.5) mm in preterm and 9.2 (+/- 4.3) mm in term infants and increased
progressively with increasing weight (P<.001) for all newborns. Mean (+/- SD)
reflex tear secretion was 7.4 (+/- 4.8) mm in preterm and 13.2 (+/- 6.5) mm in
term infants and also increased with increasing weight (P<.001) for all newborns.
CONCLUSIONS: Preterm infants have reduced reflex and basal tear secretion. This
may mask the diagnosis of a nasolacrimal duct obstruction, concentrate topically
applied medications, and allow corneas to quickly become dry during
ophthalmological examination and treatment. By term, tear production in newborns
is similar to that in adults.
PMID- 9639448
TI - The effect of age on the retardation of axial elongation following a lensectomy
in infant monkeys.
AB - OBJECTIVE: To determine the effect of age on the retardation of axial elongation
in neonatal monkey eyes following the extraction of the crystalline lens.
METHODS: A monocular lensectomy was performed on 4 rhesus monkeys when they were
4 days, 2 weeks, 7.5 months, and 1 year of age. Longitudinal measurements of
axial lengths and keratometry readings were made. RESULTS: The aphakic eye was
1.7 mm shorter than the unmanipulated fellow eye in the monkey undergoing surgery
at 4 days of age and 1.1 mm shorter in the monkey undergoing surgery at 2 weeks
of age. However, the aphakic eyes were only 0.2 mm and 0.1 mm shorter than their
unmanipulated fellow eyes, respectively, in the monkeys undergoing surgery at 7.5
months and 1 year of age. CONCLUSIONS: The retardation of axial elongation
following a lensectomy in infantile monkey eyes is age dependent. Little effect
is observed in monkeys aged 7.5 months or older.
PMID- 9639447
TI - Trifluridine, cidofovir, and penciclovir in the treatment of experimental
herpetic keratitis.
AB - OBJECTIVE: To compare trifluridine eyedrops, cidofovir eyedrops, and penciclovir
ophthalmic ointment for the treatment of herpes simplex virus type 1 keratitis.
METHODS: New Zealand white rabbits were infected with the McKrae strain of herpes
simplex virus type 1. Three days after viral inoculation, the rabbits were
randomly assigned to treatment with 1% trifluridine, 0.2% cidofovir, 3%
penciclovir ointment, or phosphate-buffered saline (for control) on various
schedules. The severity of keratitis was graded in a masked manner. RESULTS:
Treatment with any of the antiviral drugs resulted in significantly less severe
keratitis than treatment with phosphate-buffered saline. There was no
statistically significant difference between eyes given trifluridine 2, 4, or 7
times a day and eyes given cidofovir 2 times a day (P=.06, P=.43, and P=.19,
respectively, using the F test of the analysis of variance). Cidofovir given
twice a day was significantly more effective than penciclovir given either 2 or 4
times a day (P<.001 and P=.002, respectively). Even with once-a-day dosage, all 3
drugs were significantly more effective than phosphate-buffered saline (P<.001
for all). There was no significant difference between once-a-day trifluridine and
cidofovir treatments (P=.17). Trifluridine administered 5 times a day was as
effective as 1% cidofovir. A similar degree of punctate keratitis was seen after
4 to 5 days in eyes treated with trifluridine at the highest frequency, 1%
cidofovir, or penciclovir ointment. CONCLUSION: Trifluridine treatment was highly
effective in this rabbit model, even when given only once a day. Treatment with
cidofovir was as effective as that with trifluridine. CLINICAL RELEVANCE:
Cidofovir and penciclovir treatments may prove to be effective against epithelial
keratitis. Clinical trials of trifluridine, cidofovir, and penciclovir with lower
treatment frequencies appear to be warranted.
PMID- 9639449
TI - Retinal vessel changes in galactose-fed dogs.
AB - BACKGROUND: Retinal lesions similar to those in human early-stage diabetic
retinopathy have been reported to occur in dogs fed galactose for long periods.
Investigations of retinal changes, however, have been limited to studies of the
intact retinal vasculature isolated by trypsin digestion. OBJECTIVE: To document
the onset and progression of retinal lesions in galactose-fed dogs by the common
clinical techniques of fundus color photography and fluorescein angiography.
METHODS: Fourteen 6-month-old male beagles made aphakic in 1 eye were divided
into a control group (4 dogs), receiving a diet containing 30% cellulose, and a
galactosemic group (10 dogs), receiving a diet containing 30% galactose. The
progression of retinal changes in these dogs was periodically monitored by color
fundus photography and fluorescein angiography. RESULTS: Dogs fed a 30% galactose
diet for 28 to 41 months were observed by fluorescein angiography and color
fundus photography to develop, in order of frequency, microaneurysms, retinal
hemorrhages, intraretinal microvascular abnormalities, retinal nonperfused areas,
and varicose and serpiginous veins. These findings are similar to the early
clinical retinal changes observed in humans with diabetes. CONCLUSION: These
results confirm that galactosemic dogs are an appropriate and suitable animal
model for investigating human diabetic retinopathy.
PMID- 9639450
TI - A novel mutation in the GLC1A gene causes juvenile open-angle glaucoma in 4
families from the Italian region of Puglia.
AB - BACKGROUND: Primary open-angle glaucoma encompasses a complex of potentially
blinding ocular diseases characterized by a normal-appearing angle of the
anterior chamber, a characteristic degeneration of the optic nerve with resultant
typical visual field defects, and usually, an elevated intraocular pressure. It
can be subdivided into 2 groups according to the age at onset: the more prevalent
chronic open-angle glaucoma diagnosed after 40 years of age, and the less common
juvenile form, which occurs between 3 years of age and early adulthood. A locus
for primary open-angle glaucoma (GLC1A) has been mapped to a 3-centimorgan region
of the long arm of chromosome 1 (1q23-25). Recently, the myocilin (MYOC) gene,
located in this chromosomal interval, has been found mutated in several patients
affected by primary open-angle glaucoma. OBJECTIVE: To describe the clinical and
molecular genetic features of 4 pedigrees affected by autosomal dominant juvenile
open-angle glaucoma, all from the Italian region of Puglia. METHODS: Clinical
study, gonioscopy, automated perimetry, and DNA analysis were performed on
several members of the 4 families. RESULTS: We identified a new molecular defect
(1177GACA-->T) in the third exon of the GLC1A gene. This mutation is present in
all affected persons and in 2 still phenotypically normal persons. CONCLUSION:
Our results are important for diagnostic purposes because it is now possible to
identify asymptomatic carriers, for whom clinical surveillance for the early
detection and treatment of glaucoma may be suggested.
PMID- 9639451
TI - Managing oculomotor nerve palsy.
PMID- 9639452
TI - Options in the management of malignant glaucoma.
PMID- 9639453
TI - Multifocal choroiditis: clinicopathologic correlation.
AB - Many of the white dot syndromes are considered to have a granulomatous
pathogenesis. The histopathologic characteristics of this case of multifocal
choroiditis seen within 15 months of apparent clinical onset show that the white
dot lesions were nongranulomatous perivascular choroidal infiltrates, consisting
mainly of B lymphocytes. Early choroidal neovascularization was also seen.
PMID- 9639455
TI - Pars plana tube insertion of aqueous shunt with vitrectomy in malignant glaucoma.
PMID- 9639454
TI - Sarcoidosis with orbital tumor outside the lacrimal gland: initial manifestation
in 2 elderly white women.
AB - Two elderly white women (aged 72 and 87 years) were first seen with painless,
unilateral orbital swelling. Orbital scanning revealed masses infiltrating the
soft tissue around the eye. Biopsy results showed nodular, noncaseating
granulomas consistent with sarcoidosis. One patient's workup revealed systemic
manifestations of sarcoidosis at the time of examination with hilar
lymphadenopathy noted on gallium scan; the other refused a complete systemic
workup. The orbital tumors resolved with systemic prednisone therapy. To our
knowledge, our 87-year-old patient is the oldest to be seen with orbital
sarcoidosis. These 2 patients demonstrate that this diagnosis must be considered
with orbital tumors in the elderly and in unusual locations, such as these which
occurred outside the lacrimal gland.
PMID- 9639456
TI - Acute microcystic corneal epitheliopathy after daily soft contact lens wear.
PMID- 9639457
TI - Repair of a complex retinal detachment with proliferative vitreoretinopathy in an
eye with extreme scleral thinning.
PMID- 9639458
TI - Parafoveal telangiectasia in association with CREST syndrome.
PMID- 9639459
TI - Low-dose external beam irradiation for bilateral diffuse choroidal hemangioma.
PMID- 9639460
TI - Electrophysiologic evaluation of a patient with peripheral visual field
contraction associated with vigabatrin.
PMID- 9639461
TI - Iris fixation of a decentered silicone plate haptic intraocular lens: double knot
technique.
PMID- 9639462
TI - Intraorbital metallic foreign body.
PMID- 9639463
TI - Acute thioridazine retinopathy.
PMID- 9639464
TI - Use of blue-on-yellow perimetry to demonstrate quadrantanopia in multiple
sclerosis.
PMID- 9639465
TI - Erbium-YAG laser ablation: the myth of 1-microm penetration.
PMID- 9639466
TI - Optic nerve hypoplasia diagnosis should be confirmed by accurate measurements.
PMID- 9639467
TI - Interaction between acetazolamine and cyclosporine.
PMID- 9639468
TI - Botulinum toxin treatment of infantile esotropia in children.
PMID- 9639469
TI - Showing abnormal slitlamp findings.
PMID- 9639471
TI - Complement activation in sudden deafness.
AB - OBJECTIVE: To test whether complement activation is associated with sudden
deafness. DESIGN: Plasma samples obtained from patients in the acute phase of
sudden deafness were analyzed for complement activation measured by C3bc levels
and terminal complement complex. Comparisons were made with plasma samples from
healthy controls. PATIENTS: Twenty-five adult patients with unilateral sudden
deafness. The criteria for inclusion were symptoms of hearing loss for not longer
than 14 days and a hearing loss of 35 dB or more measured at entry. RESULTS:
Levels of C3bc were higher in patients compared with controls (P<.001). There
were no differences in the formation of terminal complement complex in patients
and controls. CONCLUSIONS: The elevated levels of C3bc in patients with sudden
deafness indicate an activation of the first part of the complement cascade and
therefore suspected inflammatory causes. Measurements of C3bc levels might
identify patients with sudden deafness who would benefit from treatment with anti
inflammatory drugs.
PMID- 9639470
TI - Functional results of primary closure vs flaps in oropharyngeal reconstruction: a
prospective study of speech and swallowing.
AB - BACKGROUND: The preservation of speech and swallowing function is the primary
goal when reconstructing soft tissue defects in the oral cavity or oropharynx.
The type of reconstructive procedure used should be based on outcome data
examining speech and swallowing function; yet, there is a paucity of such
information. OBJECTIVES: To present the results of a multi-institutional
prospective study of speech and swallowing function before and after soft tissue
reconstruction of the oral cavity and oropharynx, and to compare 3 methods of
reconstruction with respect to speech and swallowing function: primary closure,
distal myocutaneous flap, and microvascular free flap. DESIGN: Prospective case
comparison study. SETTING: Four leading head and neck cancer institutions.
PATIENTS: The patients were selected from a database of 284 patients treated at
the different institutions. The patients were matched for the location of the
oral cavity or oropharyngeal defect and the percentage of oral tongue and tongue
base resection. Those patients who had previous speech and swallowing deficits
and patients in whom postoperative fistulas or wound infections developed were
excluded from the study. METHODS: The patients underwent speech and swallowing
evaluation preoperatively and 3 months after healing. This evaluation included
videofluoroscopic studies of swallowing and tests of speech intelligibility and
sentence articulation. Videofluoroscopy provided measures of swallowing
efficiency and bolus movement. Liquid and paste consistencies were used in
evaluating swallowing function. MAIN OUTCOME MEASURE: The functional results of
the reconstruction. RESULTS: Patients who had primary closure were more efficient
at swallowing liquids, had less pharyngeal residue, a longer oral transit time
with paste, and higher conversational intelligibility than patients who underwent
reconstruction with a distal flap. Compared with patients who underwent
reconstruction with a free flap, those who had primary closure had more efficient
swallowing of liquids, less pharyngeal residue, and shorter pharyngeal delay
times with paste. No difference in the speech and swallowing function existed
between patients treated with distal myocutaneous flaps and those treated with
microvascular free flaps. CONCLUSION: Contrary to the current theory of oral and
oropharyngeal reconstruction, we found that the use of primary closure resulted
in equal or better function than the use of flap reconstruction in patients with
a comparable locus of resection and percentage of oral tongue and tongue base
resection.
PMID- 9639472
TI - Perineural invasion in squamous cell carcinoma of the head and neck.
AB - OBJECTIVE: To determine if perineural invasion (PNI) of small nerves affects the
outcome of patients with squamous cell carcinoma (SCC) of the upper aerodigestive
tract. DESIGN: Retrospective clinicopathological study of patients with at least
2 years of follow-up and with negative margins and no prior, synchronous, or
metachronous SCC. SETTING: Academic otolaryngology department. PATIENTS: One
hundred forty-two patients who had SCC of the oral cavity, oropharynx and
hypopharynx, or larynx resected between 1981 and 1991. INTERVENTION: Surgery with
or without adjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence was examined
with respect to PNI, nerve diameter, and microvascular or microlymphatic
invasion. Perineural invasion was correlated with lymph node metastasis,
extracapsular spread, and survival. RESULTS: Perineural invasion of nerves less
than 1 mm in diameter was present in 74 patients, lymphatic invasion in 53, and
vascular invasion in 9. Perineural invasion was significantly associated with
local recurrence (23% for PNI vs 9% for no PNI; P=. 02), and disease-specific
mortality (54% mortality for PNI vs 25% for no PNI; P<.001). With extralaryngeal
tumors, PNI was associated with nodal metastasis (73% vs 46%; P=.03). Perineural
invasion was not associated with extracapsular spread (P=.47). Microvascular
invasion, lymphatic invasion, and nerve diameter were not significantly related
to local recurrence. CONCLUSIONS: Perineural invasion of small nerves is
associated with an increased risk of local recurrence and cervical metastasis and
is, independent of extracapsular spread, a predictor of survival for patients
with SCC of the upper aerodigestive tract.
PMID- 9639473
TI - Peritumoral CD1a-positive dendritic cells are associated with improved survival
in patients with tongue carcinoma.
AB - OBJECTIVES: To determine if survival and recurrence rates for patients with
squamous cell carcinoma of the tongue correlate with the degree of dendritic cell
(DC) infiltration of the primary tumor or adjacent tongue tissue and if there is
an association between tumor or nodal stage and DC infiltration. DESIGN: Hospital
and office medical records were reviewed to obtain 5-year follow-up data.
Original pathology specimens were recut and stained for the cell surface markers
S100 and CD 1a. The number of DCs present in the specimens was quantified
microscopically and compared statistically with patient outcome and staging.
SETTING: A university hospital. PATIENTS: All patients who underwent resection of
primary squamous cell carcinoma of the tongue from January 1, 1987, through
December 31, 1990, for whom 5-year follow-up data and original pathology
specimens were available (N=43). MAIN OUTCOME MEASURES: Time to recurrence,
death, or both. RESULTS: Patients who had greater numbers of CD1a-positive DCs
adjacent to tumor had improved survival (P=.02) and decreased recurrence rates
(P=.06). The other subpopulations of DCs examined were not associated with
survival or recurrence. In addition, the number of CD 1a-positive DCs in
peritumoral epithelium decreased as the tumor stage increased (P=.01) and if
nodal metastases were present (P=.05). CONCLUSIONS: Dendritic cells are antigen
presenting cells that are thought to play a major role in the antitumor immune
response. The CD1a surface antigen has been shown to mediate T-cell interactions.
The association between CD1a-positive peritumoral DCs and patient outcome
suggests an important function for this cell population.
PMID- 9639474
TI - The ectopic parathyroid adenoma: a cost justification for routine preoperative
localization with technetium Tc 99m sestamibi scan.
AB - OBJECTIVES: To evaluate the cumulative costs of failure to identify the ectopic
parathyroid adenoma when exploration without preoperative localization is
performed and to compare these costs with the expenses of routine preoperative
localization in every patient. DESIGN: A consecutive series of 59 patients with
primary hyperparathyroidism studied with preoperative scans using technetium Tc
99m sestamibi and ultrasound was submitted to a cost analysis. A subset of 5
cases of ectopic adenomas, presumed to be unidentifiable on routine surgery, was
similarly analyzed. SETTING: Academic tertiary referral center. METHODS: The
operative, anesthesia, hospitalization, imaging, and physician reimbursement
costs of a failed exploration are compared with the costs of preoperative
technetium Tc 99m sestamibi and ultrasound scans in every patient. RESULTS: Two
cases of mediastinal parathyroid adenomas in this consecutive series of 59
patients were given a theoretical cost, including hospitalization, physician
reimbursement, and anesthesia fees. These costs were based on a failed cervical
exploration and extracted from the record of an actual patient who underwent such
a process at the University of Vermont, Burlington, in 1995. In addition, the
records of 2 patients with intrathyroidal adenomas were submitted to the same
theoretical cost analysis with the exception that these patients were assumed to
have adenomas that could be discovered after prolonged cervical exploration and
thyroid lobectomy. The net management and imaging costs for 4 cases of ectopic
parathyroid adenomas undergoing theoretical failed exploration are compared with
the cost of obtaining routine technetium Tc 99m sestamibi and ultrasound scans
for each of the 59 patients. CONCLUSION: The added cost of protracted or failed
cervical exploration nearly neutralized the costs of a routine preoperative
localization with technetium Tc 99m sestamibi and ultrasound scans.
PMID- 9639475
TI - Morphometry of paranasal sinus anatomy in chronic rhinosinusitis: a pilot study.
AB - OBJECTIVES: To test the null hypothesis that there is no relationship between
anatomical variations around the ostiomeatal complex and a predisposition to
chronic rhinosinusitis and to define such variations with increased precision.
DESIGN: Case-control study of anatomical variations in diseased and normal
sinuses. Eight homologous landmarks defining the ostiomeatal complex were located
on coronal computed tomographic scans, and their x and y coordinates were
digitized using image analysis. SUBJECTS: Ten patients with unilateral sinus
disease and 10 subjects without sinus disease (scanned for facial pain) who were
selected retrospectively by case-note analysis. RESULTS: Logistic regression
showed that the only significant spatial change predictive of a person with
rhinosinusitis was the vertical position of the middle turbinate (P=.04),
although this was not confirmed by Wilcoxon testing (P>.10). When examined by
sinus, however, the horizontal position of the uncinate process was more
laterally placed in persons with rhinosinusitis (P=.01), confirmed on Wilcoxon
testing (P=.04), but there was no significant difference when compared with
sinuses in persons without rhinosinusitis. CONCLUSIONS: Our findings suggest that
there are no anatomical differences within the ostiomeatal complex between
patients with and without rhinosinusitis. Patients with rhinosinusitis, however,
are more likely to develop it in the side with a more laterally positioned
uncinate process. Further studies, with more patients and more advanced
techniques, including thin-plate spline analysis, are indicated.
PMID- 9639476
TI - Posterior cricoidotomy lumen augmentation for treatment of subglottic stenosis in
children.
AB - OBJECTIVES: To determine the results of posterior cricoidotomy lumen augmentation
in the treatment of moderate and severe subglottic stenosis in children, and to
assess the effect of this surgery on the growth of the larynx in young children.
DESIGN: A 17-year retrospective study. PATIENTS AND METHODS: Thirteen children
with moderate and severe subglottic stenosis who underwent posterior cricoidotomy
lumen augmentation from 1980 to 1996. Eight children (62%) were male and 5 (38%)
were female. The average age was 4.7 years (age range, 8 months to 15 years). Six
(46%) of the 13 children were younger than 3 years. Nine children (69%) had
acquired subglottic stenosis, 3 of whom had a combined subglottic-posterior
glottic stenosis, and 4 (31%) had congenital subglottic stenosis. All the
children already had a tracheotomy tube placed and had undergone treatment at our
clinic or at other institutions. The surgical procedure we used included a
cricoid lamina split with grafting (2 children with costal cartilage graft and 11
with buccal mucosal graft) and stenting. RESULTS: Twelve (92%) of the 13 children
underwent decannulation, and 1 (8%) is still undergoing treatment: decannulation
is expected to be carried out in the near future. Of the 12 children who
underwent decannulation, 9 demonstrated good postoperative voice quality and 3,
who had combined subglottic-posterior glottic stenosis, developed impaired voice
function. Following stent removal, all children experienced some degree of
difficulty in swallowing saliva and liquids, which was soon overcome. No evidence
of surgery-induced laryngeal growth impairment in younger children was observed.
CONCLUSIONS: The posterior cricoidotomy lumen augmentation is a safe and
effective technique for the treatment of moderate and severe subglottic stenosis
in children of any age. This study lends further support to the assertion that
external surgery does not affect the growth of the larynx in younger children.
PMID- 9639477
TI - Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant.
AB - OBJECTIVE: To determine whether fibrin sealant can replace suture as a means of
holding a cartilage graft securely in the trachea. DESIGN: Randomized blinded
control study comparing the use of fibrin sealant vs sutures in laryngotracheal
reconstruction in ferrets. We compared results at 7 and 30 days. SUBJECTS: Forty
ferrets randomized into 2 groups of 20: fibrin sealant and sutures. Within each
group, half were studied at 7 days and the rest at 30 days. No ferrets were
withdrawn from study because of adverse effects of the intervention.
INTERVENTION: A carved costal cartilage graft was placed in the anterior cricoid
split incision, and was secured with either fibrin sealant or sutures. All
animals were extubated after recovery from anesthesia. Specimens were examined
grossly and histologically. RESULTS: All animals survived until humanely killed.
The pathologist, unaware of the groupings, measured lumen expansion in
millimeters, cartilage graft migration, mucosal in-growth, degree of
inflammation, graft integration, and graft viability. The fibrin sealant group
had statistically significant (P<.05) better results in mucosal in-growth. In no
categories was the suture group better than the fibrin sealant group. In
comparing 7-day with 30-day results, the 30-day group had significantly better
results in inflammation and graft viability. CONCLUSIONS: Fibrin sealant can be
used in place of sutures with improvement in mucosal growth in costal cartilage
laryngotracheal reconstruction in the experimental animal model. Use of fibrin
sealant (instead of sutures) may result in less surgical trauma and edema, less
surgical time, and faster recovery.
PMID- 9639478
TI - Autogenous tissue-engineered cartilage: evaluation as an implant material.
AB - OBJECTIVES: To determine whether autogenous tissue-engineered cartilage grafts
can be synthesized in predetermined shapes, to compare tissue-engineered
cartilage with native cartilage with respect to histological characteristics and
biomechanical properties, and to demonstrate how multiple transplantations affect
tissue-engineered cartilage. DESIGN: Controlled, prospective animal study.
SUBJECTS: Twenty New Zealand white rabbits, 3 weeks old. INTERVENTIONS:
Autogenous chondrocytes were seeded onto biodegradable polyglycolic acid-poly-L
lactic acid copolymer templates in 1 of 3 shapes (cross, nasal tip graft, or
auricle). Grafts and controls of sculpted cartilage were divided among 3 groups:
short-term implantation (4 or 8 weeks), long-term implantation (6 or 12 months),
and a reimplantation group. The gross morphological features, histological
findings, and tensile strength of grafts were assessed. RESULTS: Production of
tissue-engineered cartilage was confirmed in 30 of 31 implants. Histological
evaluation demonstrated characteristic cartilaginous matrix, but with prominent
vascular and fibrous tissue ingrowth. In long-term implantation grafts (n=4),
foci of osteoid were evident by 6 months. In the subset of transplanted grafts
(n=7), 5 of 7 demonstrated significant loss of cartilage viability. Tensile
strength measurements demonstrated values 24% and 41% of those of controls at 4
and 8 weeks, respectively. CONCLUSIONS: Tissue-engineered autogenous cartilage
can be reliably produced, and predetermination of graft shape is possible.
Histologically, grafts represent composites of mature cartilage infiltrated by
vasculature and fibrous tissue, with delayed osteoid formation. Graft viability
is compromised by early transplantation, and tensile strength is less than that
of native cartilage. These results demonstrate the feasibility of tissue
engineered cartilage as a future graft material.
PMID- 9639479
TI - Chronic conductive hearing loss in adults: effects on the auditory brainstem
response and masking-level difference.
AB - OBJECTIVE: To determine whether chronic conductive hearing loss in adults results
in changes in the auditory brainstem response (ABR) similar to those observed in
children with histories of otitis media with effusion. DESIGN: Test of effect of
unilateral conductive hearing loss on adult ABR using age-matched control group
and subjects as their own controls. SUBJECTS: Twelve adults with a history of
unilateral conductive ear disease. An age-matched control group of 21 adults was
also tested. METHODS: The ABR, an electrophysiologic test of auditory brainstem
functioning, was used to evaluate possible brainstem abnormalities in the
impaired listeners. In addition, the masking-level difference, a behavioral test
of binaural auditory processing in the brainstem, was used. RESULTS: When
comparing the patients' diseased ears with their healthy ears, significant delays
were seen for wave V as well as for the I-V and III-V interwave intervals. For
comparison with the control population, significant prolongations were again seen
for wave V and for the III-V interwave intervals. In addition, reduced masking
level differences and significant correlations between the masking-level
differences and the ABRs, independent of hearing threshold, were noted.
CONCLUSIONS: The results suggest that chronic conductive impairment in adults
leads to changes in the ABR similar to those observed in children with histories
of otitis media with effusion. As such, these changes do not appear to be related
to a critical period of development.
PMID- 9639480
TI - Malignant infantile osteopetrosis: otolaryngological complications and
management.
AB - OBJECTIVES: To inform otolaryngologists about upper airway obstruction requiring
tracheotomy and other otolaryngological manifestations of malignant infantile
osteopetrosis (MIOP) and to discuss pathophysiological features, management, and
new treatment strategies in MIOP. DESIGN: Ongoing case series combined with a
retrospective chart review. SETTING: International tertiary pediatric hospital.
INTERVENTIONS: Patients with MIOP were initially referred for treatment and
routine follow-up. Tracheotomy was performed to manage obstructive sleep apnea.
Audiograms were also performed at regular intervals. RESULTS: The records of 9
patients were examined. The otolaryngological findings of hearing loss,
obstructive sleep apnea (sometimes requiring tracheotomy), otitis media, and
chronic osteomyelitis with facial fistulas were identified. CONCLUSIONS:
Osteopetrosis is a rare condition caused by a failure of the osteoclast to resorb
bone. This results in thickened dense, deformed, and easily fractured bone. As a
result, growth failure, anemia, hypoplastic dentition, chronic infections, facial
fistulas, blindness, hearing loss, nasal congestion, and upper airway obstruction
may occur. The management of otolaryngological problems in a child with
osteopetrosis is an important component in comprehensive care. To our knowledge,
this study represents the largest case series of MIOP in the otolaryngology
literature.
PMID- 9639481
TI - Meniere disease caused by an anomalous vein of the vestibular aqueduct.
AB - The precise cause of Meniere disease remains unclear. Multiple causes have been
proposed with most experimental evidence pointing to impaired fluid resorption by
the endolymphatic duct and sac as the final common pathway in development of
hydrops. We report a unique case of Meniere disease secondary to compression of
the endolymphatic duct and sac by an anomalous vein of the vestibular aqueduct.
The resulting mechanical obstruction led to excessive accumulation of endolymph
with clinical signs of Meniere disease. We review the literature and discuss
proposed pathogenesis of disease. The finding of this anomalous vein provides
further evidence that anatomical obstruction of the endolymphatic duct and sac
may lead to Meniere-like symptoms. This unique example of an anatomical variant
offers additional insight into the pathophysiology of endolymphatic hydrops.
PMID- 9639482
TI - Further characterization of the DFNA1 audiovestibular phenotype.
AB - BACKGROUND: Autosomal dominant, nonsyndromic, hereditary hearing impairment in a
large Costa Rican kindred is caused by a mutation in the human homolog of the
Drosophila diaphanous gene. OBJECTIVE: To further characterize the phenotype of
DFNA1 with comprehensive audiovestibular evaluation and computed tomography of
the temporal bone. PATIENTS: One affected child and 2 affected adults of the
Costa Rican kindred who harbor a mutation in the diaphanous gene. SETTING:
Medical Center at the University of California, San Francisco. INTERVENTION:
Otologic and neuro-otologic examination; pure tone audiometry, speech audiometry,
and immitance testing; auditory evoked potentials, electrocochleography, and
otoacoustic emissions; electronystagmography and vestibular autorotation tests;
and computed tomography of the temporal bone. RESULTS: The youngest subject, an 8
year-old boy, had a mild hearing loss, intact stapedial reflexes, otoacoustic
emissions at high frequencies, normal auditory evoked potentials, and
electrocochleographic findings consistent with endolymphatic hydrops. The two
adults had severe to profound bilateral sensorineural hearing impairment.
Electronystagmography disclosed normal vestibular function. Computed tomography
demonstrated normal external, middle, and inner ear structures. CONCLUSIONS:
These results suggest that the early low-frequency hearing loss in this family is
associated with endolymphatic hydrops. Elucidation of the role of the diaphanous
gene in hearing will therefore lead to a better understanding of the mechanism of
endolymphatic hydrops.
PMID- 9639483
TI - Bilateral nasolacrimal duct obstruction managed with endoscopic techniques.
AB - We present 3 cases of bilateral acquired nasolacrimal duct obstruction secondary
to Wegener granulomatosis, sarcoidosis, and chronic lymphocytic leukemia. In all
cases significant paranasal sinus and intranasal disease coincided with bilateral
nasolacrimal duct obstruction. Surgical treatment of the nasolacrimal duct
obstruction with dacryocystorhinostomy was more successful if the paranasal sinus
disease was also treated. Nontraumatic bilateral nasolacrimal duct obstruction
heralds unusual underlying systemic diseases, and coexisting paranasal sinus
disease should be suspected. The simultaneous surgical treatment of both lacrimal
and paranasal sinus disease through an endoscopic approach is advocated.
PMID- 9639484
TI - Otolaryngological manifestations of Creutzfeldt-Jakob disease.
AB - Creutzfeldt-Jakob disease (CJD) is one of the uniformly fatal spongiform
encephalopathies that is characterized clinically by an unrelenting progression
of myoclonus, dementia, and ataxia. Since many of these patients will develop
cerebellar abnormalities, some may present to the otolaryngologist with
dizziness. Hearing loss, however, to our knowledge, has not been reported. We
describe a patient with CJD who presented with hearing loss and vague symptoms of
imbalance, and whose disease progressed rapidly and fatally despite an extensive
initial workup that was otherwise unrevealing. A review and discussion of the
otolaryngological manifestations of CJD is presented. The otolaryngologist should
be aware that CJD can present with otolaryngological manifestations, and with
proper diagnosis extensive workups may be avoided.
PMID- 9639485
TI - Minimal endoscopic approach.
PMID- 9639486
TI - Pathologic quiz case 1. Salivary gland choristoma of the middle ear.
PMID- 9639487
TI - Pathologic quiz case 2. Nasal leiomyosarcoma, low grade.
PMID- 9639488
TI - Laser-assisted uvulopalatoplasty in mild obstructive sleep apnea.
PMID- 9639489
TI - The success of LAUP in select patients with sleep-related breathing disorders.
PMID- 9639490
TI - More data needed.
PMID- 9639491
TI - Thrombopoietin and the hematopoietic stem cell.
PMID- 9639492
TI - Role of c-mpl in early hematopoiesis.
AB - Recently, several lines of evidence have indicated an expanded role for
thrombopoietin (TPO) and its receptor, c-mpl, in hematopoiesis. In addition to
being the primary physiological regulator of platelet production, it is now
apparent that TPO also acts during early hematopoiesis. To futher define the role
of TPO in early hematopoiesis we have identified discrete murine and human stem
cell populations with respect to c-mpl expression and evaluated their potential
for hematopoietic engraftment. Fluorescence-activated cell sorter analysis of
enriched stem cell populations showed the presence of c-mpl expressing
subpopulations. Approximately 50% of the murine fetal liver stem cell-enriched
population, AA4(+)Sca+c-kit+, expressed c-mpl. Analysis of the murine marrow stem
cell population LinloSca+c-kit+ showed that 70% of this population expressed c
mpl. Expression of c-mpl was also detected within the human bone marrow
CD34(+)CD38(-) stem cell progenitor pool and approximately 70% of that population
expressed c-mpl. To rigorously evaluate the role of TPO/c-mpl in early
hematopoiesis we compared the repopulation capacity of murine stem cell
populations with respect to c-mpl expression in a competitive repopulation assay.
When comparing the fetal liver progenitor populations, AA4(+)Sca+c-kit+c-mpl+ and
AA4(+)Sca+c-kit+c-mpl-, we found that stem cell activity segregates with c-mpl
expression. This result is complemented by the observation that the LinloSca+
population of c-mpl gene-deficient mice was sevenfold less potent than LinloSca+
cells from wild-type mice in repopulating activity. The engraftment potential of
the human CD34(+)CD38(-)c-mpl+ population was evaluated in a severe combined
immunodeficient-human bone model. In comparison to the CD34(+) CD38(-)c-mpl-
population, the CD34(+)CD38(-)c-mpl+ cells showed significantly better
engraftment. These results demonstrate a physiological role for TPO and its
receptor, c-mpl, in regulating early hematopoiesis.
PMID- 9639493
TI - Intracellular cytokine profile of cord and adult blood lymphocytes.
AB - Umbilical cord blood (CB) transplantation is thought to be associated with a
reduced risk of severe graft-versus-host-disease (GVHD) compared with bone marrow
transplantation (BMT). The cytokine cascade is known to be important in the
pathogenesis of GVHD; however, previous studies investigating the cytokine
secretion pattern of CB cells have been contradictory because of variations in
experimental techniques. In this study, the cytokine profile of cord and adult
blood lymphocytes and lymphocyte subsets has been assessed at the single-cell
level by flow cytometry, using CD4/CD8 and CD45RA/CD45RO markers. Cord and adult
blood mononuclear cells were stimulated with phorbol 12-myristate 13-acetate
(PMA) and ionomycin in the presence of monensin. After 4 to 24 hours of
incubation, interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-gamma), and tumor
necrosis factor-alpha (TNF-alpha) production was measured by three-color flow
cytometry. The results show that cord blood lymphocytes (CBL) produce less IL-2,
IL-4, IFN-gamma, and TNF-alpha than adult peripheral blood lymphocytes (ABL).
Further subset analysis showed that in CBL the majority of cytokine producing
cells were CD4(+)CD45RA+, whereas in ABL the cytokine-producing cells were both
CD4(+)CD45RO+ and CD8(+)CD45RO+. These results suggest that the reduced incidence
of GVHD in CB transplantation may partly due to the altered cytokine profile seen
in CBL.
PMID- 9639494
TI - Antileukemic HLA-restricted T-cell clones generated with naturally processed
peptides eluted from acute myeloblastic leukemia blasts.
AB - Recent studies have shown that transfusions of HLA-compatible donor lymphocytes
may induce complete remission in marrow-grafted patients with relapses of acute
myeloblastic leukemia (AML). We investigated the in vitro generation of
antileukemia T-cell clones obtained from the peripheral blood mononuclear cells
of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the
leukemic blasts) after stimulation with a pool of naturally processed peptides
extracted from leukemic blast cells collected at diagnosis from a patient with
hyperleucocytosis AML. We recovered a significant quantity of peptides that bound
to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte
(CTL) lines and clones specific for the eluted AML peptides and restricted to the
HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic
cells, and one clone was able to interact with the leukemic blasts from which the
naturally processed peptides had been eluted. Such T-cell clones might provide a
rationale for the development of adoptive immunotherapy and could be used to
improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft
versus-leukemia response in patients with AML.
PMID- 9639495
TI - Protease-activated receptor genes are clustered on 5q13.
AB - The serine protease, thrombin, is both a potent agonist for platelet aggregation
and a mitogen inducing the proliferation of other cell types. Many cellular
responses to thrombin are mediated by a G-protein-coupled thrombin receptor
(protease-activated receptor-1, PAR-1). This represents the prototype of a new
family of proteolytically cleaved receptors that includes PAR-2 and the recently
identified PAR-3. Like PAR-1, PAR-3 is a potential thrombin receptor. Their
similar gene structure, mechanism of activation, and colocalization to 5q13
raises the question of a common evolutionary origin and of their belonging to a
clustered gene family. Construction of a physical map of the 5q13 region by
pulsed-field gel electrophoresis (PFGE) has allowed us to identify six potential
CpG islands and to establish a linkage of the PAR genes. Southern blot analysis
showed that they were in a cluster on a 560-kb Asc I fragment, in the order PAR
2, PAR-1, and PAR-3. PAR-1 and PAR-2 genes were contained within the identical
240-kb Not I fragment, thus confirming a tight linkage between them. The
localization of other CpG islands suggested that more PAR-family genes may be
present.
PMID- 9639496
TI - Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte
colony-stimulating factor receptor gene associated with severe chronic
neutropenia.
AB - Mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene are
found in a number of patients with severe chronic neutropenia predisposed to
acute myeloid leukemia. These mutations result in the absence of the C-terminal
domain of the G-CSF-R, a region which has been implicated in differentiation
signaling. We generated mice with an equivalent mutation (gcsfr-triangle
Delta715) by homologous and Cre-mediated recombination in embryonic stem cells.
Both wt/triangle Delta715 and triangle Delta715/triangle Delta715 mice have
significantly reduced numbers of blood neutrophils compared with their wt/wt
littermates. However, under continuous G-CSF administration mutant mice develop
peripheral neutrophil counts that significantly exceed those of wild-type
littermates. These findings indicate that depending on G-CSF levels in mice, the
triangle Delta715 mutation can contribute both to neutropenia and to
neutrophilia.
PMID- 9639497
TI - Prostaglandin E2 induces resistance to human immunodeficiency virus-1 infection
in monocyte-derived macrophages: downregulation of CCR5 expression by cyclic
adenosine monophosphate.
AB - The chemokine receptor CCR5 can function as a coreceptor for human
immunodeficiency virus-1 (HIV-1) entry into CD4(+) T cells and macrophages,
especially during the early stages of HIV-1 infection. The regulation of CCR5
expression may affect not only leukocyte migration, but also infectivity by HIV-1
and, therefore, acquired immunodeficiency syndrome (AIDS) pathogenesis. We report
here that agents which increase intracellular concentrations of cyclic adenosine
monophosphate (cAMP) rapidly downregulate CCR5 gene expression, with consequent
loss of CCR5 expression and function in monocytes/macrophages. Chemotaxis and
intracellular Ca2+ mobilization in monocytes pretreated with prostaglandin E2 or
dibutyryl-cAMP for 24 hours were significantly reduced in response to the CCR5
ligand, MIP-1beta. Moreover, HIV-1 entry into monocyte-derived macrophages
pretreated with dibutyryl-cAMP or prostaglandin E2 was markedly decreased. Our
findings suggest that resistance to HIV-1 can be induced by agents which increase
cellular levels of cAMP and that this may suggest additional therapeutic
strategies to limit infection by HIV-1.
PMID- 9639498
TI - Concentrations of thrombopoietin in bone marrow in normal subjects and in
patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential
thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.
AB - The function of bone marrow (BM) stromal thrombopoietin (TPO) in megakaryopoiesis
remains unknown. In the present study we attempted to clarify the
pathophysiological implications of stromal TPO in normal subjects (NS) and in
patients with idiopathic thrombocytopenic purpura (ITP), aplastic anemia (AA),
and essential thrombocythemia (ET) by measuring TPO concentrations in BM and
peripheral blood (PB) and by estimating the levels of stromal TPO mRNA with
TaqMan fluorescence-based post-reverse transcription-polymerase chain reaction
product detection system. The results showed that TPO concentrations in PB were
significantly elevated in patients with ITP (34.9 +/- 11.7 pg/mL) and AA (364.1
+/- 153.5 pg/mL) but within normal range in patients with ET (each 20.0 and 22.1;
NS, 22.1 +/- 8.2 pg/mL). In all subjects, the TPO concentrations in BM correlated
well with the PB levels, and the former were consistently higher than the latter.
The concentrations of TPO in BM also correlated with the levels of TPO mRNA in
stromal cells. Furthermore, expression levels of TPO mRNA clearly correlated with
megakaryocyte counts in NS and patients with ITP, indicating that stromal TPO
actually enhances megakaryopoiesis. Thus, our results in the present study
indicate that TPO from BM stromal cells is considered to play an essential role
for megakaryopoiesis under various patho-physiological conditions.
PMID- 9639499
TI - Detection and titration of human herpesvirus-8-specific antibodies in sera from
blood donors, acquired immunodeficiency syndrome patients, and Kaposi's sarcoma
patients using a whole virus enzyme-linked immunosorbent assay.
AB - A human herpesvirus-8 (HHV-8) enzyme-linked immunosorbent assay (ELISA) with a
whole virus lysate as antigen was developed and used to measure the
seroprevalence rate and levels of IgG antibodies to HHV-8 in sera/plasma of
various patient groups and blood donors. The virus antigen was prepared from the
KS-1 cell line, which produces lytic virus, and therefore contains a broad array
of viral proteins. Seroprevalence studies using this ELISA showed the following:
10 of 91 blood donors (11%) had an average HHV-8 antibody titer of 118; 67 of 72
(93%) classic Kaposi's sarcoma (KS) patients were positive with an average titer
of 14,111; and 57 of 62 (92%) KS/human immunodeficiency virus (HIV) patients were
positive with an average titer of 4,000. A study on a very limited number of
serial serum samples from patients before and after diagnosis with KS showed
highly elevated antibody titers to HHV-8 virus after KS lesions developed.
Preliminary data show that 50% of the sera from HIV-1(+) homosexual patients
contain IgG antibodies to HHV-8 suggesting that this population is at high risk
for developing KS. Antibody results correlated well with the confirmatory
immunofluorescent assays (IFA) using KS-1 cells as the substrate. This HHV-8 IgG
antibody detection ELISA is sensitive and specific and does not cross-react with
Epstein-Barr virus (EBV) or other human herpesviruses. The results of this HHV-8
antibody survey suggest that this rapid ELISA assay can be used to screen large
numbers of sera to find those at risk for developing KS.
PMID- 9639500
TI - The redox state as a correlate of senescence and wasting and as a target for
therapeutic intervention.
AB - The loss of body cell mass (bcm) in senescence and wasting is poorly understood.
We now show that the plasma cystine/acid soluble thiol ratio, ie, an indicator of
the redox state, is increased in old age and cancer patients and correlated with
a decrease in bcm and plasma albumin. A cause/effect relationship was suggested
by two independent studies with N-acetyl-cysteine (NAC). NAC caused an increase
in the bcm of healthy persons with high plasma cystine/thiol ratios, and
treatment of cancer patients with NAC plus interleukin-2 caused an increase in
bcm, plasma albumin, and functional capacity. Albumin levels below 680 micromol/L
were associated with an increase in body water. Our studies suggest that the
shift in the redox state may contribute to the loss of bcm and may provide a
quantitative guideline for therapeutic intervention. Treatment of cancer patients
with thiol-containing antioxidants may improve the quality of life.
PMID- 9639501
TI - Treatment of anemia in myelodysplastic syndromes with granulocyte colony
stimulating factor plus erythropoietin: results from a randomized phase II study
and long-term follow-up of 71 patients.
AB - Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic
syndromes (MDS) in approximately 20% of patients. Previous studies have suggested
that treatment with the combination of granulocyte colony-stimulating factor (G
CSF) and epo may increase this response rate. In the present phase II study,
patients with MDS and anemia were randomized to treatment with G-CSF + epo
according to one of two alternatives; arm A starting with G-CSF for 4 weeks
followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks
followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory
anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27
refractory anemia with excess blasts [RAEB]) were included in the study, three
were evaluable only for epo as monotherapy and 47 for the combined treatment. The
overall response rate to G-CSF + epo was 38%, which is identical to that in our
previous study. The response rates for patients with RA, RARS, and RAEB were 20%,
46%, and 37%, respectively. Response rates were identical in the two treatment
groups indicating that an initial treatment with G-CSF was not neccessary for a
response to the combination. Nine patients in arm B showed a response to the
combined treatment, but only three of these responded to epo alone. This suggests
a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71
evaluable patients from both the present and the preceding Scandinavian study on
G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic
transformation during a median follow-up of 43 months was 28%. Twenty patients
entered long-term maintenance treatment and showed a median duration of response
of 24 months. The international prognostic scoring system (IPSS) was effective to
predict survival, leukemic transformation, and to a lesser extent, duration of
response, but had no impact on primary response rates.
PMID- 9639502
TI - Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's
lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA).
AB - Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse
prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and
scarcity, the outcomes of the different histological subtypes have not been
compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive
non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed
for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and
1,595 (85%) had BCL. According to the Kiel classification, most PTCL were
classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell
(PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with
BCL patients, the former had more disseminated disease (78% v 58%), B symptoms
(57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%),
and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more
bulky disease (41% v 26%). According to the International Prognostic Index (IPI),
PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and
22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and
PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5
year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free
survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different
histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%)
was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%)
NHL. When multivariate analysis was applied using the IPI score as one factor,
nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the
poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse
prognostic factors at diagnosis, this study shows that the T-cell phenotype is an
independent significant factor, which should be incorporated into the definition
of prognostic groups.
PMID- 9639503
TI - Sustained gene expression in retrovirally transduced, engrafting human
hematopoietic stem cells and their lympho-myeloid progeny.
AB - Inefficient retroviral-mediated gene transfer to human hematopoietic stem cells
(HSC) and insufficient gene expression in progeny cells derived from transduced
HSC are two major problems associated with HSC-based gene therapy. In this study
we evaluated the ability of a murine stem cell virus (MSCV)-based retroviral
vector carrying the low-affinity human nerve growth factor receptor (NGFR) gene
as reporter to maintain gene expression in transduced human hematopoietic cells.
CD34(+) cells lacking lineage differentiation markers (CD34(+)Lin-) isolated from
human bone marrow and mobilized peripheral blood were transduced using an
optimized clinically applicable protocol. Under the conditions used, greater than
75% of the CD34(+) cell population retained the Lin- phenotype after 4 days in
culture and at least 30% of these expressed a high level of NGFR (NGFR+) as
assessed by fluorescence-activated cell sorter analysis. When these CD34(+)Lin
NGFR+ cells sorted 2 days posttransduction were assayed in vitro in clonogenic
and long-term stromal cultures, sustained reporter expression was observed in
differentiated erythroid and myeloid cells derived from transduced progenitors,
and in differentiated B-lineage cells after 6 weeks. Moreover, when these
transduced CD34(+)Lin-NGFR+ cells were used to repopulate human bone grafts
implanted in severe combined immunodeficient mice, MSCV-directed NGFR expression
could be detected on 37% +/- 6% (n = 5) of the donor-type human cells recovered 9
weeks postinjection. These findings suggest potential utility of the MSCV
retroviral vector in the development of effective therapies involving gene
modified HSC.
PMID- 9639504
TI - Interleukin-7 influences the development of thymic dendritic cells.
AB - Interleukin-7 (IL-7) has been shown to be a critical factor in B and T
lymphopoiesis, and to influence the differentiation of myeloid cell lineages. In
the present study we extend these results demonstrating that IL-7 also plays an
important role in the development of thymic dendritic cells (DC). The addition of
IL-7 to rat fetal thymus organ cultures (FTOC) resulted in a drastic increase in
the number of CD3(-)CD4(-)CD8(-) cells, which mostly expressed typical DC
markers, including major histocompatibility complex class II, OX-62, CD11b, CD68,
and CD54. These cells exhibited morphological and ultrastructural features of DC,
and were potent stimulators of the allogeneic mixed leukocyte reaction. Although
increased numbers of DC were continuously generated throughout the culture period
in the presence of IL-7, they were not actively dividing, indicating that DC in
IL-7-treated cultures did not arise by expansion of pre-existing cells. Reduced
DC numbers obtained after the addition of neutralizing anti-IL-7 antibodies to
mouse FTOC confirmed the relevance of endogenously produced IL-7 on thymic DC
development. Furthermore, the addition of IL-7 to FTOC derived from severe
combined immunodeficient mice also generated large numbers of DC in the absence
of thymocyte maturation.
PMID- 9639505
TI - Involvement of Fas-mediated apoptosis in the hematopoietic progenitor cells of
graft-versus-host reaction-associated myelosuppression.
AB - The influence of graft-versus-host (GVH) reaction on the host hematopoietic cells
clinically manifests itself both as adverse reactions in transfusion-associated
GVH disease (GVHD) and as a therapeutic graft-versus-leukemia (GVL) effect in
either donor lymphocytes transfusion (DLT) or allogeneic bone marrow (BM)
transplantation. We examined the effect of GVH reaction on the host hematopoiesis
in the murine parent-into-F1 (P1 --> F1) model of GVHD. The systemic transfer of
5 x 10(7) of C57BL/6 (B6) splenocytes into (B6xDBA/2)F1 mice (BDF1), which
results in acute GVHD, reduced the peripheral blood cell counts, the number of BM
cells, and colony-forming unit-granulocyte macrophage (CFU-GM), whereas the
injection of 10(8) of DBA/2 cells into BDF1, which results in chronic GVHD, did
not affect hematopoiesis 2 weeks after the transfer. To clarify the mechanism of
such myelosuppression, we examined the Fas expression in both hematopoietic
progenitor cells as well as whole BM cells. The Fas expressions in each fraction
significantly increased in BDF1 mice 2 weeks after the induction of acute GVHD,
whereas no such effects were observed in the BDF1 mice with chronic GVHD.
Furthermore, when such BM cells were incubated with anti-Fas antibody (Jo2),
which induces apoptosis through Fas, the fraction of apoptotic cells increased
and the number of CFU-GM decreased significantly. The in vivo administration of
neutralizing anti-FasL antibody into BDF1 mice receiving with B6 spleen cells
thus protected the host mice from BM failure. These results indicate that the
functional expression of Fas on hematopoietic cells plays an essential role in
the myelosuppressive effect of GVHD.
PMID- 9639506
TI - Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice.
AB - The MLL (ALL-1, HRX) gene is frequently involved in chromosomal translocations in
acute leukemia and has homology with Drosophila trithorax, which controls
homeobox gene expression and embryogenesis. To elucidate the function of Mll, we
generated mice with a mutated Mll locus. Mice with a homozygous mutation were
embryonic lethal and died at embryonic day 11.5 to 14.5, showing edematous bodies
and petechiae. Histological examination revealed that hematopoietic cells were
decreased in the liver of homozygous embryos, although they were composed of
erythroid, myeloid, monocytic, and megakaryocytic cells with normal
differentiation. Colony-forming assays using cells from fetal livers and yolk
sacs showed that the number of colonies was markedly reduced and many of the
colonies delayed to be recognized in Mllmu/mu embryos, although some of the
colonies from Mllmu/mu embryos developed similarly with that from Mll+/+ and
Mll+/mu embryos, suggesting the delayed onset of the proliferation of
hematopoitic precursors. These data show that the hematopoietic precursors were
greatly reduced in mutant mice, and suggest that Mll functions as a regulator of
the growth of hematopoietic precursors.
PMID- 9639507
TI - Bifurcated dendritic cell differentiation in vitro from murine lineage phenotype
negative c-kit+ bone marrow hematopoietic progenitor cells.
AB - We have recently established the culture system to generate dendritic cells (DCs)
from murine Lin-c-kit+ bone marrow hematopoietic progenitor cells (HPCs) in the
presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell
factor (SCF) + tumor necrosis factor-alpha (TNF-alpha). We present here the
identification of two DC precursor subsets originated from HPCs with the
phenotype of CD11b-/dullCD11c+ and CD11b+hiCD11c+ that develop independently at
early time points (days 4 to 6) in the same culture conditions. Both of CD11b
/dullCD11c+ and CD11b+hiCD11c+ precursors could differentiate at day 10 to 14
into CD11b-/dullCD11c+ mature DCs with typical morphology, phenotype, and the
ability to stimulate allogenic mixed leukocyte reaction (MLR). However, the
endocytic capacity of fluorescein isothiocyanate-dextran was markedly reduced
during the differentiation. CD11b-/dullCD11c+ precursors expressed high levels of
Ia, CD86, CD40, and E-cadherin molecules, but not c-fms transcript, and mature
DCs derived from this precursor subset continue to express abundant E-cadherin
antigen, a discernible marker for Langerhans cells. In contrast, CD11b+hiCD11c+
precursors expressed c-fms mRNA, but low levels of Ia, CD86, and E-cadherin,
whereas CD40 was undetectable. CD11b-/dullCD11c+ mature DCs differentiated from
these precursors displayed abundant c-fms mRNA and nonspecific esterase activity.
Interestingly, CD11b+hiCD11c+ precursors, but not CD11b-/dullCD11c+ precursors,
may be bipotent cells that can be induced by M-CSF to differentiate into
macrophages. All of these results suggest that CD11b-/dullCD11c+ and
CD11b+hiCD11c+ cells are distinct DC precursors derived from Lin-c-kit+ HPCs,
which differentiate into mature DCs through bifurcated and independent DC
differentiation pathways.
PMID- 9639508
TI - Induction of synaptosomal-associated protein-23 kD (SNAP-23) by various
cytokines.
AB - Cytokines manifest their function through regulation of gene expression. We
searched for immediate-early cytokine responsive genes by the mRNA differential
display technique using interleukin-3 (IL-3)-dependent OTT-1 cells, and have
isolated a novel cDNA which encodes 210 amino acids and shows 87% amino acid
identity to human SNAP-23 (synaptosomal-associated protein of 23 kD). The message
for this protein (mouse SNAP-23) was induced in OTT-1 cells by IL-3, granulocyte
macrophage colony-stimulating factor (GM-CSF), and IL-5. The experiment using C
terminal deletion mutants of the common beta subunit (betac) of IL-3/GM-CSF/IL-5
receptors showed that expression of SNAP-23 was associated with the Ras-Raf-MAPK
pathway, but not with the JAK-STAT pathway. Moreover, SNAP-23 was induced in
response to a wide variety of cytokines, including IL-2, IL-3, IL-5, IL-10, stem
cell factor, G-CSF, GM-CSF, leukemia inhibitory factor, and erythropoietin.
Constitutive expression of SNAP-23 was seen in various tissues, including heart,
lung, kidney, liver, spleen, and small intestine. Possible involvement of SNAP-23
in cytokine signal transduction is discussed.
PMID- 9639509
TI - Some human inhibitor antibodies interfere with factor VIII binding to factor IX.
AB - Factor VIII (fVIII) functions as a cofactor of factor IXa in the intrinsic
pathway of blood coagulation. Its absence or abnormality causes the bleeding
disorder hemophilia A. About 23% of hemophiliacs who receive therapeutic fVIII
infusions develop antibodies that inhibit its activity. We previously showed by
inhibitor neutralization assays that the fVIII A2 and C2 domain polypeptides
contain common inhibitor epitopes. Often hemophilic inhibitor plasmas were
partially neutralized by C2 and more completely neutralized by fVIII light chain
(A3-C1-C2), suggesting the presence of an additional major inhibitor epitope(s)
within the A3-C1 domains. In immunoprecipitation assays, 17 of 18 inhibitor IgGs
bound to recombinant 35S-A3-C1. Amino acids 1811-1818 of the A3 domain comprise a
binding site for factors IX and IXa. Three inhibitor IgGs prevented binding of
factor IXa to fVIII light chain, and the binding of each IgG to light chain was
competed by A3 peptide 1804-1819. The generation of factor Xa by the fVIIIa/fIXa
complex in a chromogenic assay was prevented by these inhibitors. Therefore, we
propose that another important mechanism of fVIII inactivation by human
inhibitors is the prevention of fVIIIa/fIXa association.
PMID- 9639510
TI - Cancer procoagulant and tissue factor are differently modulated by all-trans
retinoic acid in acute promyelocytic leukemia cells.
AB - All-trans-retinoic acid (ATRA) downregulates the expression of two cellular
procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human
promyelocytic leukemia cells. To evaluate whether or not changes of the
procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto
differentiation process, we have characterized the effect of ATRA on the TF and
CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4
derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and
NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental
cells of three synthetic retinoid analogues, ie: AM580 (selective for the
retinoic acid receptor [RAR] alpha), capable to induce the granulocytic
differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437
(selective for RARgamma), both lacking this capability. Cells were treated with
either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on
cell differentiation was evaluated by morphologic changes, cell proliferation,
nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33
and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal
Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient
plasmas. Further TF and CP have been characterized and quantified in cell-sample
preparations by chromogenic and immunological assays. In the first series of
experiments, ATRA downregulates both TF and CP in NB4 parental cells, as
expected. However, in the differentiation-resistant cell lines, it induced a
significant loss of TF but had little or no effect on CP. In a second series of
experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell
maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto
differentiating effects and did not affect CP levels. On the other hand, in the
same cells the TF expression was reduced by ATRA and AM580, but also by the
RARbeta agonist CD2019, which did not induce cell maturation. These data indicate
that in NB4 cells, ATRA modulation of CP occurs in parallel with signs of cell
differentiation, while the regulation of TF appears to be at least in part
independent from these processes, and involves both alpha and beta nuclear
retinoid receptors.
PMID- 9639511
TI - The P2Y1 receptor is necessary for adenosine 5'-diphosphate-induced platelet
aggregation.
AB - The human P2Y1 receptor heterologously expressed in Jurkat cells behaves as a
specific adenosine 5'-diphosphate (ADP) receptor at which purified adenosine
triphosphate (ATP) is an ineffective agonist, but competitively antagonizes the
action of ADP. This receptor is thus a good candidate to be the elusive platelet
P2T receptor for ADP. In the present work, we examined the effects on ADP-induced
platelet responses of two selective and competitive P2Y1 antagonists, adenosine
2'-phosphate-5'-phosphate (A2P5P) and adenosine-3'-phosphate-5'-phosphate
(A3P5P). Results were compared with those for the native P2Y1 receptor expressed
on the B10 clone of rat brain capillary endothelial cells (BCEC) and for the
cloned human P2Y1 receptor expressed on Jurkat cells. A2P5P and A3P5P inhibited
ADP-induced platelet shape change and aggregation (pA2 = 5) and competitively
antagonized calcium movements in response to ADP in fura-2-loaded platelets, B10
cells, and P2Y1-Jurkat cells. In contrast, these compounds had no effect on ADP
induced inhibition of adenylyl cyclase in platelets or B10 cells, whereas known
antagonists of platelet activation by ADP such as Sp-ATPalphaS were effective.
These identical signaling responses and pharmacologic properties suggest that
platelets and BCEC share a common P2Y1 receptor involved in ADP-induced
aggregation and vasodilation, respectively. This P2Y1 receptor coupled to the
mobilization of intracellular calcium stores was found to be necessary to trigger
ADP-induced platelet aggregation. The present results, together with data from
the literature, also point to the existence of another as yet unidentified ADP
receptor, coupled to adenylyl cyclase and responsible for completion of the
aggregation response. Thus, the term, P2T, should no longer be used to designate
a specific molecular entity.
PMID- 9639512
TI - Anticoagulant effects of 1alpha,25-dihydroxyvitamin D3 on human myelogenous
leukemia cells and monocytes.
AB - The hormonally active form of vitamin D is 1alpha, 25-dihydroxyvitamin D3
[1,25(OH)2D3], which is a principal regulator of calcium homeostasis. It also
affects hormone secretion, cell differentiation, and proliferation by a mode of
action that involves stereospecific interaction with an intracellular vitamin D
receptor (VDR). We recently found that retinoids, which are vitamin A
derivatives, exert anticoagulant effects by upregulating thrombomodulin (TM) and
downregulating tissue factor (TF) expression in acute promyelocytic leukemia
cells and monoblastic leukemia cells. Both the VDR and retinoid receptors belong
to the same family of receptors. A heterodimer consisting of the retinoid X
receptor and the VDR binds to vitamin D responsive elements on genes regulated by
vitamin D. To determine whether 1,25(OH)2D3 would exhibit anticoagulant effects
similar to retinoids, we measured the antigen level, activity, and mRNA level of
TM and TF in human leukemic cells, vascular endothelial cells, and monocytes
treated with 1,25(OH)2D3. We found that 1,25(OH)2D3 upregulates antigen
expression, activity, and mRNA levels of TM and downregulates antigen expression,
activity, and mRNA levels of TF in human monocytic leukemia cells, some acute
myelogenous leukemia cells, and monocytes, but not in umbilical vein endothelial
cells. Transient transfection studies with reporter plasmids in monocytic
leukemia cells and mobility gel-shift assay showed interaction with 1,25(OH)2D3
and functional retinoic acid responsive elements present in the 5'-flanking
region of the TM gene. However, auxiliary factors or other elements in the TM
gene may contribute to VDR specificity and transactivation of the gene in
specific target cells. These findings indicate that 1,25(OH)2D3 resembles the
retinoids in its control of the transcription of the TM and TF genes in human
monocytic cells. Analogs of 1,25(OH)2D3 with anticoagulant activity may serve as
adjunctive antithrombotic agents in monocytic leukemia and atherosclerotic
disease.
PMID- 9639513
TI - Targeted inactivation of the coagulation factor IX gene causes hemophilia B in
mice.
AB - Hemophilia B is a leading target for gene therapy because current therapy is not
optimal. Hence, a murine model of factor IX (F. IX) deficiency was generated to
develop gene therapy strategies for hemophilia B. A targeting vector was created
by replacing a 3.2-kb segment of the gene encompassing the catalytic domain with
a phosphoglycerokinase promoter-driven neomycin resistant (neor) gene cassette.
The transfected embryonic stem cell clones generated chimeric male mice, and germ
line transmission of the inactivated F. IX gene was observed in their offsprings.
Southern analysis confirmed the mutant genotype in hemizygous male and carrier
female mice. F. IX transcripts were not detected in liver RNA isolated from
hemizygous mice, and lower levels of F. IX mRNA were noted in carrier female mice
when compared with those of normal litter mates. As expected, the mean F. IX
coagulant titer of affected male mice was 2.8 U/dL (n = 10), while the mean F. IX
titer of carrier female mice was 35 U/dL (n = 14), compared with 69 U/dL (n = 9)
for the normal female mice and 92 U/dL (n = 22) for normal male and female litter
mates. Further, the tail bleeding time of hemizygous mice was markedly prolonged
(>3 hours) compared with those of normal and carrier female litter mates (15 to
20 minutes). Seven of 19 affected male mice died of exsanguination after tail
snipping, and two affected mice died of umbilical cord bleeding. Currently, there
are 10 affected mice surviving at 4 months of age. Aside from the factor IX
defect, the carrier female and hemizygous male mice had no liver pathology by
histologic examination, were fertile, and transmitted the F. IX gene mutation in
the expected Mendelian frequency. Taken together, we have generated a F. IX
knockout mouse for evaluation of novel gene therapy strategies for hemophilia B.
PMID- 9639514
TI - Naturally occurring mutations in glycoprotein Ibalpha that result in defective
ligand binding and synthesis of a truncated protein.
AB - The platelet GPIb-V-IX complex is the receptor for the initial binding of von
Willebrand factor (vWF) mediating platelet adhesion. The complex is composed of
four membrane-spanning glycoproteins (GP): GPIbalpha, GPIbbeta, GPIX, and GPV.
Bernard-Soulier syndrome results from a qualitative or quantitative defect in one
or more components of the platelet membrane GPIb-V-IX complex. We describe the
molecular basis of a novel Bernard-Soulier syndrome variant in two siblings in
whom GPIbalpha was not detected on the platelet surface but that was present in a
soluble form in plasma. DNA sequence analysis showed that the affected
individuals were compound heterozygotes for two mutations. One, inherited from a
maternal allele, a T777 --> C point mutation in GPIbalpha converting Cys65 -->
Arg within the second leucine rich repeat, the other, a single nucleotide
substitution (G2078 --> A) for the tryptophan codon (TGG) causing a nonsense
codon (TGA) at residue 498 within the transmembrane region of GPIbalpha,
inherited from a mutant paternal allele. The Bernard-Soulier phenotype was
observed in siblings who were compound heterozygotes for these two mutations.
Although GPIbalpha was not detected on the surface of the patient's platelets,
soluble GPIbalpha could be immunoprecipitated from plasma. When plasmids encoding
GPIbalpha containing the Cys65 --> Arg mutation were transiently transfected into
Chinese hamster ovary (CHO) cells stably expressing the GPbeta-IX complex
(CHObetaIX), the expression of GPIbalpha was similar to the wild-type (WT)
GPIbalpha, but did not bind vWF. When plasmids encoding GPIbalpha containing the
Trp498 --> stop were transiently transfected into CHObetaIX, the surface
expression of GPIbalpha was barely detectable compared with the WT GPIbalpha.
Thus, this newly described compound heterozygous defect produces Bernard-Soulier
syndrome by a combination of synthesis of a nonfunctional protein and of a
truncated protein that fails to insert into the platelet membrane and is found
circulating in plasma.
PMID- 9639515
TI - Construction and characterization of a fusion protein of single-chain anti-CD20
antibody and human beta-glucuronidase for antibody-directed enzyme prodrug
therapy.
AB - The CD20 antigen is an attractive target for specific treatment of B-cell
lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific
activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a
tumor-specific antibody such as anti-CD20. We constructed a fusion protein of the
single-chain Fv anti-CD20 mouse monoclonal antibody (MoAb) 1H4 and human beta
glucuronidase for the activation of the nontoxic prodrug N-[4-doxorubicin-N
carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate to doxorubicin at the
tumor site. The cDNAs encoding the light- and heavy-chain variable regions of 1H4
were cloned, joined by a synthetic sequence encoding a 15-amino acid linker and
fused to human beta-glucuronidase by a synthetic sequence encoding a 6-amino acid
linker. An antibody-enzyme fusion protein-producing cell line was established by
transfection of the construct into human embryonic kidney 293/EBNA cells. The
yield of active fusion protein was 100 ng/mL transfectoma supernatant. Antibody
affinity, antibody specificity, and enzyme activity were fully retained by the
fusion protein. Immunoprecipitation and analysis by sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) showed that the fusion protein has
a relative molecular weight (Mw) of 100 kD under denaturing conditions. Gel
filtration analysis indicated that the enzymatically active form of the fusion
protein is a tetramer with an Mw of approximately 400 kD. The nontoxic prodrug N
[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate was
hydrolyzed by the fusion protein at a hydrolysis rate similar to that of human
beta-glucuronidase. When the fusion protein was specifically bound to Daudi
lymphoma cells, the prodrug induced similar antiproliferative effects as
doxorubicin. Thus, it is feasible to construct a eukaryotic fusion protein
consisting of a single-chain anti-CD20 antibody and human beta-glucuronidase for
future use in the activation of anticancer prodrugs in B-cell lymphoma.
PMID- 9639516
TI - Localization of receptors for vasoactive intestinal peptide, somatostatin, and
substance P in distinct compartments of human lymphoid organs.
AB - Regulatory peptides, such as vasoactive intestinal peptide (VIP), somatostatin
(SS), or substance P (SP), are considered to play a role in immune regulation. To
localize the targets of these peptides in the human immune system, their
receptors have been evaluated with in vitro receptor autoradiography in lymph
nodes, tonsils, appendix, Peyer's patches, spleen, and thymus. The three peptide
receptors were detected in all lymphoid tissues tested, but, unexpectedly,
usually in distinct compartments. In lymph nodes, palatine tonsils, vermiform
appendix, and Peyer's patches, VIP receptors were found in the CD3 positive zone
around lymphoid follicles; SS receptors in the germinal centers of secondary
follicles; and SP receptors mainly in interfollicular blood vessels. In the
spleen, VIP receptors were detected in periarterial lymphatic sheaths, SS
receptors in the red pulp, and SP receptors in the central arteries. In the
thymus, VIP receptors were present in cortex and medulla, SS receptors in the
medulla, and SP receptors in blood vessels. For comparison, cholecystokinin (CCK)
A and -B receptors were not demonstrated in any of these tissues. These results
suggest a strong compartmentalization of the three peptide receptors in human
lymphoid tissues and represent the molecular basis for the understanding of a
very complex and interactive mode of action of these peptides.
PMID- 9639517
TI - Expression of the CD8alpha beta-heterodimer on CD8(+) T lymphocytes in peripheral
blood lymphocytes of human immunodeficiency virus- and human immunodeficiency
virus+ individuals.
AB - CD8(+) T lymphocytes play a pivotal role in controlling human immunodeficiency
virus (HIV)-1 replication in vivo. We have performed four-color flow cytometric
analysis of CD8(+) peripheral blood lymphocytes (PBL) from 21 HIV-1 seronegative
and 103 seropositive individuals to explore the phenotypic heterogeneity of
CD8beta-chain expression on CD8(+) T lymphocytes and to clarify how its
expression on CD8(+) T lymphocytes may relate to acquired immunodeficiency
syndrome (AIDS) clinical progression. We showed that the single monoclonal
antibody (MoAb) 2ST8-5H7, directed against the CD8alpha beta-heterodimer,
identifies CD8(+) T lymphocytes as effectively as the conventional combination of
anti-CD3 and anti-CD8alpha antibodies. However, we detected a significantly lower
mean fluorescence (MF) of anti-CD8alpha beta staining on PBL from HIV-1
seropositive donors as compared with seronegative donors. In fact, CD8(+) T
lymphocytes from HIV-1-infected individuals with the lowest CD4 counts showed the
lowest levels of CD8alpha beta MF. To explore further this change in CD8alpha
beta expression, we assessed the expression of 14 different cell surface
molecules on CD8alpha beta+ T lymphocytes of PBL from 11 HIV-1 seronegative and
22 HIV-1 seropositive individuals. The MF of anti-CD8alpha beta staining was
significantly reduced on CD8(+) T lymphocyte subsets that showed immunophenotypic
evidence of activation. The subset of lymphocytes expressing low levels of
CD8alpha beta expressed higher levels of activation, adhesion, and cytotoxic
associated molecules and was predominantly CD45RO+ and CD28(-). Finally, we
monitored the expression of the CD8alpha beta-heterodimer on PBL of eight HIV-1
infected individuals over a 16-week period after the initiation of highly active
antiretroviral therapy (HAART), including zidovudine (ZDV), lamivudine (3TC), and
indinavir (IDV), and found a significant increase in the expression of the
CD8alpha beta-heterodimer. These results suggest that antibodies recognizing the
CD8alpha beta-heterodimer are useful tools to specifically identify CD8(+) T
lymphocytes. Moreover, the quantitative monitoring of CD8alpha beta expression
allows the detection of discrete CD8(+) T lymphocyte subsets and may be useful
for assessing the immune status of individuals infected with HIV-1.
PMID- 9639518
TI - Adhesion, transendothelial migration, and reverse transmigration of in vitro
cultured dendritic cells.
AB - Dendritic cells (DC) are migratory cells which exhibit complex trafficking
properties in vivo, involving interaction with vascular and lymphatic endothelium
and extracellular matrix (ECM). The underlying mechanisms involved in these
processes are still ill defined. In the present study we have investigated the
ability of DC to interact in vitro with human vascular endothelial cells (EC) and
ECM. DC were differentiated from monocytes by in vitro exposure to granulocyte
macrophage colony-stimulating factor and interleukin-13 for 7 days. In adhesion
assays a considerable proportion of DC bound to resting EC monolayers: (17% +/-
4%, mean +/- SE of eight experiments). Adhesion to tumor necrosis factor (TNF)
activated EC was increased to 29% +/- 5% (n = 8). Binding to resting EC was
strongly inhibited by anti-CD11a and CD11b, but not by CD11c monoclonal
antibodies (MoAbs); on TNF-activated EC, anti-VLA-4 in concert with anti-CD18
inhibited adhesion by more than 70%. Binding to a natural ECM, derived from
cultured EC, or to purified fibronectin was high: 52% +/- 6% (n = 8) involved VLA
4 and VLA-5 integrins. In a transmigration assay, 10% +/- 2% (n = 6) of input
cells were able to cross the EC monolayer. Unlike adhesion, transendothelial
migration was significantly reduced by anti-CD31 MoAb. The amount of DC
transmigrated through a monolayer of EC was increased twofold to threefold by a
defined set of C-C chemokines including RANTES, MIP1alpha, MIP5, and, to a lesser
extent, by MIP1beta and MCP-3. Most importantly, in view of the trafficking
pattern of these cells, a significant proportion of DC (13% +/- 4% of input cells
seeded) was able to migrate across the endothelial basement membrane and,
subsequently, across the endothelial barrier (reverse transmigration). The
adhesion molecules and chemoattractants characterized herein are likely to
underlie the complex trafficking of DC in vivo.
PMID- 9639519
TI - Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized
blood products: a mechanism for monocyte-mediated suppression of T-cell
proliferation.
AB - Previous reports showed that granulocyte colony-stimulating factor (G-CSF)
mobilized peripheral blood mononuclear cells (G-PBMC) are hyporesponsive to
alloantigen compared with control PBMC. In the current study, neutralizing
antibodies to interleukin-10 (IL-10) increased the proliferative response of G
PBMC to alloantigen by 50. 14% (+/- 12.79%; n = 8), whereas the proliferative
response of control PBMC was not affected. The inhibition of OKT3-stimulated CD4
cell proliferation by G-PBMC-derived CD14(+) cells could also be abrogated by the
addition of IL-10 neutralizing antibodies. Further, IL-10 levels correlated with
the number of CD14 cells in these cultures. Constitutive IL-10 mRNA levels
detected by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)
were 10-fold higher in G-PBMC compared with control PBMC. This translated into
significantly higher IL-10 levels after 24-hour lipopolysaccharide (LPS)
stimulation of G-PBMC compared with control PBMC (P = .036). IL-10 mRNA levels
were also fivefold higher in isolated G-PBMC-derived CD14 cells compared with
control CD14 cells. This corresponded to increased constitutive production of IL
10 by isolated G-PBMC-derived CD14 cells compared with control CD14 cells (357.2
+/- 104.5 v 51.7 +/- 30.5, P = .051). In conclusion, these data suggest that
monocytes contained within G-PBMC, which, in comparison to marrow, are increased
in absolute number and relative proportion to T cells, may suppress T-cell
responsiveness by secretion of IL-10.
PMID- 9639521
TI - Microsatellite instability and frameshift mutations in BAX and transforming
growth factor-beta RII genes are very uncommon in acute lymphoblastic leukemia in
vivo but not in cell lines.
AB - Mutations in the DNA mismatch repair (MMR) system lead to an instability of
simple repetitive DNA sequences involved in several cancer types. This
instability is reflected in a high mutation rate of microsatellites, and recent
studies in colon cancer indicate that defects in MMR result in frequent
frameshift mutations in mononucleotide repeats located in the coding regions of
BAX and transforming growth factor-beta (TGF-beta) receptor genes. Circumstantial
evidence suggests that the MMR defect may be involved in some lymphoid
malignancies, although several allelotype analyses have concluded on the low
level of microsatellite instability in acute lymphoblastic leukemias. To further
evaluate the implication of MMR defects in leukemogenesis, we have studied a
series of 98 children with acute lymphoblastic leukemia and 14 leukemic cell
lines using several indicators of MMR defects. Microsatellite markers were
compared between blast and normal DNA from the same patients and mutations were
sought in mononucleotide repeat sequences of BAX and TGF-beta receptor II (TGF
beta RII). The absence of microsatellite instability (MI) and the absence of
mutations in the genes examined from patient's leukemic cells contrasted with the
observation that half of the cell lines displayed a high degree of MI and that
three of seven of these mutator cell lines harbored mutations in BAX and/or TGF
beta RII. From these results we conclude that MMR defects are very uncommon in
freshly isolated blasts but are likely to be selected for during the
establishment of cell lines.
PMID- 9639520
TI - Differential effects of chondroitin sulfates A and B on monocyte and B-cell
activation: evidence for B-cell activation via a CD44-dependent pathway.
AB - At inflammatory sites, proteoglycans are both secreted by activated mononuclear
leukocytes and released as a consequence of extracellular matrix degradation.
Chondroitin 4-sulfate proteoglycans constitute the predominant ones produced by
activated human monocytes/macrophages. In this study, we show that two
chondroitin 4-sulfate forms, CSA and CSB, can activate distinct peripheral blood
mononuclear cell types. Whereas CSA activates monocytes (to secrete monokines),
CSB activates B-cells (to proliferate). In contrast, the chondroitin 6-sulfate
CSC and heparin do not exert these functional effects. We further show that CD44
monoclonal antibodies block CSB-induced B-cell proliferation. These findings
point to glycosaminoglycans, and specifically chondroitin 4-sulfates, as a novel
class of immunological mediators at inflammatory sites. Furthermore, the data
link CD44 to B-cell activation, paralleling the established roles of CD44 in T
cell and monocyte activation.
PMID- 9639522
TI - Chromosomal and gene amplification in diffuse large B-cell lymphoma.
AB - Chromosomal translocations leading to deregulation of specific oncogenes
characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL).
To characterize additional genetic features that may be of value in delineating
the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis
consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC)
for incidence of gene amplification, a genetic abnormality previously shown to be
associated with tumor progression and clinical outcome. A subset of 20 cases was
subjected to comparative genomic hybridization (CGH) analysis, which identified
nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14,
13q32, 16p12, 18q21-22, and 22q12). Candidate amplified genes mapped to these
sites were selected for further analysis based on their known roles in lymphoid
cell and lymphoma development, and/or history of amplification in tumors. Probes
for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2
(18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern
blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or
more copies) with incidence ranging from 11% to 23%. This analysis is consistent
with our previous finding that REL amplification is associated with extranodal
presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4,
and MDM2 amplification was associated with advanced stage disease. These data
show, for the first time, that amplification of chromosomal regions and genes is
a frequent phenomenon in DLBL and demonstrates their potential significance in
lymphomagenesis.
PMID- 9639523
TI - Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: support for
the hypothesis that protection is mediated via inhibition of the JNK/SAPK
pathway.
AB - The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma
cells from apoptosis induced by anti-fas antibodies and dexamethasone was
studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle
distribution or activation of RAF-1 or ERK in dexamethasone- or anti-fas-treated
8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability
correlated with an inhibition of dexamethasone- and anti-fas-induced activation
of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that
cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also
inhibited c-jun function in 8226 cells via introduction of a mutant dominant
negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to
anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone
induced apoptosis. These results support the notion that IL-6 protects MM cells
against anti-fas through its inhibitory effects on JNK/c-jun but indicate
protection against dexamethasone occurs through separate, yet unknown pathways.
PMID- 9639524
TI - Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell
lymphoma cells.
AB - In this study we investigated the role of interleukin-15 (IL-15) in the
immunobiology of cutaneous T-cell lymphoma (CTCL) cells. Using cell culture
techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and
immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the
Sezary cell line SeAx and that both cytokines prolonged the survival of malignant
T cells directly isolated from Sezary syndrome (SS) patients. Both IL-15 and IL-7
were more potent than IL-2. IL-4 and IL-9, whose receptors share the same gamma
chain with the receptors of IL-2, IL-7, and IL-15, did not sustain the growth of
CTCL cells, indicating that signaling through the common gamma chain (gammac) is
not sufficient for continuous growth. IL-13 and tumor necrosis factor-alpha (TNF
alpha) had no effect. IL-7 and IL-15 also supported the growth of SeAx cells in
the presence of the apoptosis inducing agents dexamethasone and retinoic acid.
The analysis of patient Sezary cells and three CTCL cell lines by RT-PCR showed
that all these cells expressed IL-15 mRNA, but only a few (25%) produced IL-7
mRNA. Immunohistological analyses of skin biopsy samples of SS and Mycosis
fungoides patients showed immunoreactivity for IL-15 in basal cell layer
keratinocytes and in the infiltrating lymphocytes. We conclude that IL-15 is a
growth or viability factor for CTCL-derived cell lines or shortly cultivated
Sezary cells. The findings that IL-15 mRNA can be detected in Sezary syndrome
peripheral blood mononuclear cells and that the IL-15 protein is detected in skin
sections from CTCL patients suggest that IL-15 plays an important role in the
biology of CTCL.
PMID- 9639525
TI - Prednisolone resistance in childhood acute lymphoblastic leukemia: vitro-vivo
correlations and cross-resistance to other drugs.
AB - As an important determinant of response to chemotherapy, accurate measurement of
cellular drug resistance may provide clinically relevant information. Our
objectives in this study were to determine the relationship between in vitro
resistance to prednisolone (PRD) measured with the colorimetric methyl-thiazol
tetrazolium (MTT) assay, and (1) short-term clinical response to systemic PRD
monotherapy, (2) long-term clinical outcome after combination chemotherapy within
all patients and within the subgroups of clinical good and poor responders to
PRD, and (3) in vitro resistance to 12 other drugs in 166 children with newly
diagnosed acute lymphoblastic leukemia (ALL). The 12 clinical poor PRD responders
had ALL cells that were median 88-fold more in vitro resistant to PRD than 131
good responders (P = .013). Within all patients, increased in vitro resistance to
PRD predicted a significantly worse long-term clinical outcome, at analyses with
and without stratification for clinical PRD response, and at multivariate
analysis (P = .001). Within both the clinical good and poor responder
subgroups, increased in vitro resistance to PRD was associated with a worse
outcome, which was significant within the group of clinical good responders (P <
.001). LC50 values, ie, lethal concentrations to 50% of ALL cells, for PRD and
each other drug correlated significantly with those of all other 12 drugs, with
an average correlation coefficient of 0.44 (standard deviation 0.05). The highest
correlations were found between structurally related drugs. In conclusion, in
vitro resistance to PRD was significantly related to the short-term and long-term
clinical response to chemotherapy, the latter also within the subgroup of
clinical good responders to PRD. There was a more general in vitro cross
resistance between anticancer drugs in childhood ALL, although drug-specific
activities were recognized.
PMID- 9639526
TI - Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia
without clinical evidence of neurofibromatosis, type 1.
AB - Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic syndrome
that is associated with neurofibromatosis, type 1 (NF1). The NF1 tumor suppressor
gene encodes neurofibromin, which regulates the growth of immature myeloid cells
by accelerating guanosine triphosphate hydrolysis on Ras proteins. The purpose of
this study was to determine if the NF1 gene was involved in the pathogenesis of
JMML in children without a clinical diagnosis of NF1. An in vitro transcription
and translation system was used to screen JMML marrows from 20 children for NF1
mutations that resulted in a truncated protein. Single-stranded conformational
polymorphism analysis was used to detect RAS point mutations in these samples. We
confirmed mutations of NF1 in three leukemias, one of which also showed loss of
the normal NF1 allele. An NF1 mutation was detected in normal tissue from the
only patient tested and this suggests that JMML may be the presenting feature of
NF1 in some children. Activating RAS mutations were found in four patients; as
expected, none of these samples harbored NF1 mutations. Because 10% to 14% of
children with JMML have a clinical diagnosis of NF1, these data are consistent
with the existence of NF1 mutations in approximately 30% of JMML cases.
PMID- 9639527
TI - The evolution of B precursor leukemia in the Emu-ret mouse.
AB - Emu-ret mice carrying an RFP/RET fusion gene under the transcriptional control of
the immunoglobulin heavy chain enhancer develop B lineage leukemias/lymphomas. We
have characterized B-cell development in these mice before the onset of clinical
disease to determine the steps involved in leukemogenesis. Flow cytometry reveals
that the CD45R+CD43(+)CD24(+)BP-1(+) late pro-B-cell population is markedly
expanded in the bone marrow of 3- to 5-week-old Emu-ret mice. Compared with late
pro-B cells from transgene-negative mice, Emu-ret late pro-B cells have a limited
capacity to differentiate in interleukin (IL)-7 and a higher incidence of VDJ
rearrangements, but a similar cell cycle profile. In contrast,
CD45R+CD43(+)CD24(+)BP-1(-) early pro-B cells from 3- to 5-week-old Emu-ret mice,
which also express the RFP/RET transgene, differentiate in IL-7 similarly to
their normal counterparts. Furthermore, early pro-B cells from Emu-ret and
transgene-negative mice have an identical pattern of growth inhibition when
exposed to interferons (IFNs)-alpha/beta and -gamma, whereas, pro-B-cell leukemia
lines derived from Emu-ret mice are markedly less sensitive to growth inhibition
by these IFNs. In 13-week-old well-appearing Emu-ret mice, late pro-B cells
upregulate CYCLIN D1 expression and downregulate CASPASE-1 expression in a
pattern that correlates with the emergence of B precursor cells in the peripheral
blood and the loss of other B lineage subsets in the bone marrow. Taken together,
these results suggest that the expression of the RFP/RET transgene initially
prevents the normal elimination of late pro-B cells with nonproductive
rearrangements. Secondary events that simultaneously disturb the normal
transcriptional regulation of genes involved in the control of the cell cycle and
apoptosis may allow for subsequent malignant transformation within the expanded
late pro-B-cell population.
PMID- 9639528
TI - Complement fragment-induced release of neutrophils from bone marrow and
sequestration within pulmonary capillaries in rabbits.
AB - Infusion of complement fragments induces rapid sequestration of neutrophils
within the pulmonary capillaries. This study examined the contributions of the
bone marrow (BM) and the liver to the accumulation of neutrophils within the
lungs. Complement fragments induced the release of neutrophils from the BM within
7 minutes of infusion, and these neutrophils sequestered in the lungs immediately
upon reaching the pulmonary capillaries. Neutrophils expressing high levels of L
selectin were preferentially retained within the pulmonary microvasculature. By
30 minutes after the infusion was stopped, the circulating neutrophil counts had
increased, primarily because of release from the BM. The number of neutrophils
sequestered in the lung had decreased by only 27%, and the number of neutrophils
in the liver increased by 223%. These studies indicate that complement fragments
induce the release of neutrophils from the BM far more rapidly than previously
described. These newly released neutrophils immediately sequester within the
lung, increasing the number of neutrophils available to injure the lung many fold
beyond the number that were circulating before infusion. The preferential
retention of L-selectin-expressing neutrophils likely reflects the requirement
for L-selectin-mediated adhesion in maintaining sequestered neutrophils within
the pulmonary microvasculature. The number of circulating neutrophils reflects a
balance between pulmonary sequestration, rapid release from the BM, and uptake by
the liver and other organs.
PMID- 9639529
TI - Epstein-Barr virus infects and induces apoptosis in human neutrophils.
AB - The role of neutrophils during Epstein-Barr virus (EBV) infection is not known.
Disruption of the initial and nonspecific immune response may favor the spread of
EBV infection. We have previously shown that EBV interacts with human neutrophils
and modulates protein expression. In this study we have investigated the ability
of EBV to infect neutrophils. Electron microscopy studies showed penetration of
virus and its subsequent localization to the nucleus. The presence of viral
genomes in isolated nuclei from neutrophils was also shown by polymerase chain
reaction (PCR). Expression of viral transcripts like EBNA-2 (Epstein-Barr nuclear
antigen-2) and ZEBRA (BamHI Z EBV replication activator) was not detected by
reverse transcriptase (RT)-PCR, suggesting that EBV does not seem to establish a
latent or a lytic infection in neutrophils. However, at 20 hours post-EBV
infection, 77% of cells were apoptotic as compared to 22% in uninfected cell
cultures, as evaluated by flow cytometry. This EBV-induced apoptosis was
prevented by the addition of granulocyte-macrophage colony-stimulating factor to
the cell cultures. Apoptotic cell death seems to implicate the Fas/Fas ligand (L)
pathway, as reflected by an increase of Fas/Fas L expression on neutrophils
treated with EBV and an increase of soluble Fas L, which may function in an
autocrine/paracrine pathway to mediate cell death. Lastly, EBV genome was
detected from neutrophils of infectious mononucleosis (IM) patients in contrast
to neutrophils obtained from healthy EBV-seropositive donors. Our findings on the
interactions of EBV with neutrophils will then provide new insights on the
immunosuppressive effects associated with EBV infection.
PMID- 9639530
TI - Intracellular storage and regulated plasma membrane expression of human
complement receptor type 1 in rat basophil leukemia cell transfectants.
AB - Polymorphonuclear neutrophils (PMN) contain multiple distinct secretory
compartments that are sequentially mobilized during cell activation. Complement
receptor type 1 (CR1) is a marker for a readily mobilizable secretory vesicle
compartment, which can undergo exocytic fusion with the plasma membrane
independently of secretion of traditional granule contents. The basis for the
formation of these distinct compartments is incompletely understood. Primary and
secondary granules are generated directly from the Golgi complex during different
stages of development of the cell, obviating the need for sorting signals for
proper packaging of their constituents. To determine whether the secretory
vesicles are formed in a similar manner, we studied a stable rat basophilic
leukemia cell line (RBL-CR1) transfected with a plasmid containing the cDNA of
human CR1 driven by a viral promoter. The CR1 was present primarily
intracellularly in small vesicles resembling the CR1 storage pools in resting
PMN. Activation of RBL-CR1 resulted in translocation of intracellular CR1 to the
plasma membrane, with mobilization requirements different from those of the
classical RBL granules. Thus, in RBL-CR1, continuously synthesized CR1 is stored
and upregulated in much the same way as in PMN. This suggests that differential
timing of gene expression is not essential for proper storage of CR1 and that
other sorting mechanisms are involved, which can be studied in RBL-transfectants.
PMID- 9639531
TI - An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5
reductase in humans.
AB - Two forms of NADH-cytochrome b5 reductase (b5R), an erythrocyte-restricted
soluble form, active in methemoglobin reduction, and a ubiquitous membrane
associated form involved in lipid metabolism, are produced from one gene. In the
rat, the two forms are generated from alternative transcripts differing in the
first exon, however, biogenesis of human b5R was less understood. Recently, two
different transcripts (M and S), differing in the first exon were also described
in humans. Here, we have investigated the tissue-specificity and the role of the
S-transcript in the generation of soluble b5R. By RNase protection assays
designed to simultaneously detect alternative b5R transcripts in the same sample,
the S transcript was undetectable in nonerythroid and in erythroleukemic K562
cells induced to differentiate, but was present in terminal erythroblast
cultures, and represented a major b5R transcript in reticulocytes. Analysis of
the translation products of the M- and S-transcripts in HeLa cells transfected
with the corresponding cDNAs demonstrated that the S-transcript generates soluble
b5R, presumably from an internal initiation codon. Our results indicate that the
S-transcript is expressed at late stages of erythroid maturation to generate
soluble b5R.
PMID- 9639532
TI - Analysis of the human ferrochelatase promoter in transgenic mice.
AB - Ferrochelatase catalyzes the chelation of ferrous iron and protoporphyrin to form
heme. It is expressed as a housekeeping gene in all cells, but is upregulated
during erythropoiesis. Ferrochelatase activity is deficient in the inherited
disease protoporphyria as a result of heterogeneous mutations. Although human
ferrochelatase is transcribed from a single promoter in both nonerythroid and
erythroid cells, previous studies using transient transfection assays failed to
demonstrate erythroid-specific increased expression from 4.0 kb of the human
ferrochelatase promoter containing the erythroid cis-elements, GATA and NF-E2.
The present study analyzes the in vivo regulation of the ferrochelatase gene to
provide insights into the mechanism of its erythroid-specific enhancement.
Transgenic (TG) mouse lines were generated in which the luciferase reporter gene
was driven by either a 150-bp ferrochelatase minimal promoter (-0.15 TG) or by a
4.0 kb extended 5' upstream region (-4.0 TG). Expression of the -4.0 TG transgene
was generally consistent with the endogenous gene during embryonic development
and in nonerythroid and erythroid tissues as demonstrated by Northern blotting
and mRNA in situ hybridization. The -4.0 TG was expressed at a higher level than
the -0.15 TG in nonerythroid and erythroid tissues, including during
extramedullary erythropoiesis induced by n-acetylphenylhydrazine injection. The
enhanced erythroid expression of the -4.0 TG correlates with the appearance of a
DNase I hypersensitive site in the 5' flanking region of the transgene.
Therefore, in the context of chromosomal integration, the 5' flanking region of
the ferrochelatase gene is necessary and sufficient to confer high levels of
transgene expression in erythroid tissue.
PMID- 9639533
TI - Temporal synthesis of band 3 oligomers during terminal maturation of mouse
erythroblasts. Dimers and tetramers exist in the membrane as preformed stable
species.
AB - Band 3, the anion transport protein of the erythrocyte membrane, exists in the
membrane as a mixture of dimers (B3D) and tetramers (B3T). The dimers are not
linked to the skeleton and constitute the free mobile band 3 fraction. The
tetramers are linked to the skeleton by their interaction with ankyrin. In this
report we have examined the temporal synthesis and assembly of band 3 oligomers
into the plasma membrane during red cell maturation. The oligomeric state of
newly synthesized band 3 in early and late erythroblasts was analyzed by size
exclusion high-pressure liquid chromatography of band 3 extracts derived by mild
extraction of plasma membranes with the nonionic detergent C12E8 (octaethylene
glycol n-dodecyl monoether). This analysis revealed that at the early
erythroblast stage, the newly synthesized band 3 is present predominantly as
tetramers, whereas at the late stages of erythroid maturation, it is present
exclusively as dimers. To examine whether the dimers and tetramers exist in the
membrane as preformed stable species or whether they are interconvertible, the
fate of band 3 species synthesized during erythroblast maturation was examined by
pulse-chase analysis. We showed that the newly synthesized band 3 dimers and
tetramers are stable and that there is no interconversion between these species
in erythroblast membranes. Pulse-chase analysis followed by cellular
fractionation showed that, in early erythroblasts, the newly synthesized band 3
tetramers are initially present in the microsomal fraction and later incorporated
stably into the plasma membrane fraction. In contrast, in late erythroblasts the
newly synthesized band 3 dimers move rapidly to the plasma membrane fraction but
then recycle between the plasma membrane and microsomal fractions. Fluorescence
photobleaching recovery studies showed that significant fractions of B3T and B3D
are laterally mobile in early and late erythroblast plasma membranes,
respectively, suggesting that many B3T-ankyrin complexes are unattached to the
membrane skeleton in early erythroblasts and that the membrane skeleton has yet
to become tightly organized in late erythroblasts. We postulate that in early
erythroblasts, band 3 tetramers are transported through microsomes and stably
incorporated into the plasma membrane. However, when ankyrin synthesis is
downregulated in late erythroblasts, it appears that B3D are rapidly transported
to the plasma membrane but then recycled between the plasma membrane and
microsomal compartments. These observations may suggest novel roles for membrane
skeletal proteins in stabilizing integral membrane protein oligomers at the
plasma membrane and in regulating the endocytosis of such proteins.
PMID- 9639534
TI - To GpIb or not to GpIb.
PMID- 9639535
TI - Serglycin expression during monocytic differentiation of U937-1 cells.
AB - Serglycin is the major proteoglycan in most hematopoietic cells, including
monocytes and macrophages. The monoblastic cell line U937-1 was used to study the
expression of serglycin during proliferation and differentiation. In unstimulated
proliferating U937-1 cells serglycin mRNA is nonconstitutively expressed. The
level of serglycin mRNA was found to correlate with the synthesis of chondroitin
sulfate proteoglycan (CSPG). The U937-1 cells were induced to differentiate into
different types of macrophage-like cells by exposing the cells to PMA, RA, or
VitD3. These inducers of differentiation affected the expression of serglycin
mRNA in three different ways. The initial upregulation seen in the normally
proliferating cells was not observed in PMA treated cells. In contrast, RA
increased the initial upregulation, giving a reproducible six times increase in
serglycin mRNA level from 4 to 24 h of incubation, compared to a four times
increase in the control cells. VitD3 had no effect on the expression of serglycin
mRNA. The incorporation of (35S)sulfate into CSPG decreased approximately 50% in
all three differentiated cell types. Further, the (35S)CSPGs expressed were of
larger size in PMA treated cells than controls, but smaller after RA treatment.
This was due to the expression of CSPGs, with CS-chains of 25 and 5 kDa in PMA
and RA treated cells, respectively, compared to 11 kDa in the controls. VitD3 had
no significant effect on the size of CSPG produced. PMA treated cells secreted
75% of the (35S)PGs expressed, but the major portion was retained in cells
treated with VitD3 or RA. The differences seen in serglycin mRNA levels, the
macromolecular properties of serglycin and in the PG secretion patterns, suggest
that serglycin may have different functions in different types of macrophages.
PMID- 9639536
TI - Site localization of sialyl Lewis(x) antigen on alpha1-acid glycoprotein by high
performance liquid chromatography-electrospray mass spectrometry.
AB - A simple, fast and sensitive method was developed to verify the presence of the
sialyl Lewis(x) antigen on an N-linked glycoprotein. High performance liquid
chromatography-electrospray mass spectrometry (HPLC-ESI/MS) was used to identify
which of the five N-linked glycosylation sites of human plasma alpha1-acid
glycoprotein (orosomucoid, OMD) contain the sialyl Lewis(x) antigen. OMD was
digested with proteolytic enzymes and analyzed by reversed phase chromatography
coupled with on-line ESI/MS. A tandem mass spectrometry experiment was designed
to detect the presence of the sialyl Lewis(x) antigen based on the observation of
an 803 mass to charge ratio ( m/z ) ion produced in the intermediate pressure
region of the ESI interface. The ESI/MS signal at m/z 803 is consistent with an
oxonium ion for a glycan structure containing NeuAc, Gal, GlcNAc, and Fuc. The
identity of the m/z 803 ion was confirmed by ESI/MS/MS analysis of the m/z 803
fragment ion and comparison with a sialyl Lewis(x) standard. The stereochemistry
and linkage positions were assigned using previous NMR analysis but could be
determined with permethylation analysis if necessary. The analysis of OMD gave a
pattern showing signal for the sialyl Lewis(x) antigen coeluting with each of the
five N-linked glycopeptides. The ability to monitor sialyl Lewis(x) expression at
each of the five sites is of interest in the study of OMD's role in inflammatory
diseases.
PMID- 9639537
TI - GPI anchor biosynthesis in yeast: phosphoethanolamine is attached to the alpha1,4
linked mannose of the complete precursor glycophospholipid.
AB - Cells synthesize the GPI anchor carbohydrate core by successively adding N
acetylglucosamine, three mannoses, and phosphoethanolamine (EtN-P) onto
phosphatidylinositol, thus forming the complete GPI precursor lipid which is then
added to proteins. Previously, we isolated a GPI deficient yeast mutant
accumulating a GPI intermediate containing only two mannoses, suggesting that it
has difficulty in adding the third, alpha1,2-linked Man of GPI anchors. The
mutant thus displays a similar phenotype as the mammalian mutant cell line S1A-b
having a mutation in the PIG-B gene. The yeast mutant, herein named gpi10-1 ,
contains a mutation in YGL142C, a yeast homolog of the human PIG-B. YGL142C
predicts a highly hydrophobic integral membrane protein which by sequence is
related to ALG9, a yeast gene required for adding Man in alpha1,2 linkage to N
glycans. Whereas gpi10-1 cells grow at a normal rate and make normal amounts of
GPI proteins, the microsomes of gpi10-1 are completely unable to add the third
Man in an in vitro assay. Further analysis of the GPI intermediate accumulating
in gpi10 shows it to have the structure Manalpha1-6(EtN-P-)Manalpha1-4GlcNalpha1
6(acyl) Inositol-P-lipid. The presence of EtN-P on the alpha1,4-linked Man of GPI
anchors is typical of mammalian and a few other organisms but had not been
observed in yeast GPI proteins. This additional EtN-P is not only found in the
abnormal GPI intermediate of gpi10-1 but is equally present on the complete GPI
precursor lipid of wild type cells. Thus, GPI biosynthesis in yeast and mammals
proceeds similarly and differs from the pathway described for Trypanosoma brucei
in several aspects.
PMID- 9639538
TI - Cloning and expression of an alpha-2,8-polysialyltransferase (STX) from Xenopus
laevis.
AB - Polysialic acid (polySia) is a carbohydrate structure found on neural cell
adhesion molecules (N-CAM). Two polysialyltransferases (polySiaTs) that catalyze
synthesis of polySia have been described, and designated PST-1/PST/ST8SiaIV and
STX/ST8SiaII. We cloned a polySiaT (xSTX) from a nonmammalian vertebrate, Xenopus
laevis . xSTX had 80% amino acid similarity to the rat STX. This clone induced
polySia expression when transfected into polySia-negative COS-1 cells. Northern
blot analysis of whole embryos at different stages of development revealed that
xSTX mRNA was most abundantly expressed in premetamorphic stages. The relative
level of xSTX and N-CAM mRNAs was also examined and found to change in parallel
to the extent of polysialylation on N-CAM. In adult tissues, the expression of
xSTX mRNA was restricted to brain, eye and heart, which also expressed polySia.
These results suggest that xSTX is the major enzyme responsible for the synthesis
of polysialylated N-CAM in embryos at certain stages of development and also in
adult tissues.
PMID- 9639539
TI - Structural characterization and independent folding of a chimeric glycoprotein
comprising granulocyte-macrophage colony stimulating factor and erythropoietin
sequences.
AB - MEN 11300 is a hybrid glycoprotein of 297 amino acids obtained by fusion of the
cDNA encoding GM-CSF with the cDNA encoding EPO followed by transfection of the
hybrid gene into CHO cells. The oligonucleotide construct incorporated a spacing
sequence between the two individual cDNAs which encodes eight amino acids
constituting a linker peptide intended to separate the GM-CSF and EPO moieties.
The recombinant MEN 11300 protein was submitted to a detailed structural
characterization including the verification of the entire amino acid sequence,
the assignment of the disulfide bridges pattern, the identification of the
glycosylation sites and the definition of the glycosidic moiety, including site
specificity. Partial processing of the C-terminal Arg residue and the occurrence
of N-glycosylation sites at Asn27, Asn155, Asn169, Asn214 were established.
Moreover, O-glycosylation at Ser257 and at the N-terminal region was also
detected. A large heterogeneity was observed in the N-glycans due to the presence
of differently sialylated and fucosylated branched complex type oligosaccharides
whereas O-linked glycans were constituted by GalGalNAc chains with a different
number of sialic acids. The disulfide bridges pattern was established by direct
FABMS analysis of the proteolytic digests or by ESMS analysis of HPLC purified
fractions. Pairing of the eight cysteine residues resulted in Cys54-Cys96, Cys88
Cys121, Cys138-Cys292, and Cys160-Cys164. This S-S bridges pattern is identical
to that occurring in the individual natural GM-CSF and EPO, thus showing that the
two protein moieties in MEN 11300 can independently acquire their native three
dimensional structure.
PMID- 9639540
TI - Coordinated binding of sugar, calcium, and antibody to macrophage C-type lectin.
AB - Mouse macrophage galactose/N-acetylgalactosamine-specific C-type lectin (MMGL) is
a type II transmembrane glycoprotein belonging to the C-type lectin family. Our
development of monoclonal antibodies led us to discover that a calcium-dependent
conformational change is detected by an antibody (termed mAb LOM-11) and that the
antibody's binding to the respective site locks the lectin in an active
conformation. These findings correspond to the divalent cation-mediated
regulatory mechanisms in a family of cell adhesion molecule integrins that have
gained much attention. We now provide direct evidence that mAb LOM-11 increases
the affinity of the lectin for calcium ions as a mechanism for the conformational
lock using a soluble recombinant form of MMGL (rML) produced in bacteria.
Furthermore, we discovered by using an enzyme-linked immunosorbent assay that
specific monosaccharides induced a binding site for mAb LOM-11 on the immobilized
rML under low calcium environments. We also demonstrated that cell surface MMGL
on a transfectant cell line underwent a conformational change upon addition of
calcium or ligands, as detected by the binding of mAb LOM-11. These properties
are reminiscent of ligand-induced binding sites defined for integrins. The
present results suggest a possibility that the mAb LOM-11 binding site on the
lectin may be a site at which protein-protein interaction helps to fine tune the
specificity of the C-type lectins by means of coordinated recognition mechanisms.
PMID- 9639541
TI - Fucosebeta-1-P-Ser is a new type of glycosylation: using antibodies to identify a
novel structure in Dictyostelium discoideum and study multiple types of
fucosylation during growth and development.
AB - Three antibodies that recognize distinct fucose epitopes were used to study
fucosylation during growth and development of Dictyostelium discoideum. mAb83.5
is known to recognize an undefined "fucose epitope" on several proteins with
serine-rich domains, while mAb CAB4, and a component of anti-horse-radish
peroxidase, specifically recognize Fucalpha1,6GlcNAc and Fucalpha1,3GlcNAc
residues respectively in the core of N-linked oligosaccharides. We show that mAb
83.5 defines a new type of O-glycosylation. Serine-containing peptides incubated
with GDPbeta[3H]Fuc and microsomes formed two fucosylated products. A neutral
product accounting for 30% of the label did not react with the antibody, while
the rest of the label was incorporated into a charged product which contained all
the mAb83.5 reactive material. beta-Elimination of the labeled peptide or
endogenous products produced [3H]Fuc-1-P, indicating phosphodiester linkage to
serine. Fucbeta-1-P and GDP-betaFuc at 100 microM blocked mAb83.5 binding to
endogenous and peptide products, but their alpha-linked anomers did not.
Electrospray ionization mass spectra of the neutral and anionic labeled products
showed major peaks of mass units corresponding to O-Fuc-Ser peptide and O-Fuc
phospho-Ser peptide, respectively. The activity of Fuc-phosphotransferase exactly
paralleled the accumulation of reactive glycans during growth and development.
The expressions of N-glycan core Fucalpha1,6GlcNAc and Fucalpha1,3GlcNAc and
their respective fucosyl transferase activities were also synchronous, but their
developmental regulation differed from one another. Fucalpha1, 6GlcNAc was
expressed maximally during growth but declined during development. In contrast
core Fucalpha1,3GlcNAc epitopes were expressed almost exclusively during
development. These findings provide direct evidence for a novel type of O
phosphofucosylation, demonstrate the existence of an O-fucosyl transferase, and
identify two different types of core fucosylation in the N-glycans of
Dictyostelium.
PMID- 9639542
TI - alpha-N-acetylgalactosamine-capping of chondroitin sulfate core region
oligosaccharides primed on xylosides.
AB - We previously reported that cultured mammalian cells incubated with 4
methylumbelliferyl (MU) or p -nitrophenyl (pNP) beta-xyloside synthesize an alpha
GalNAc-terminated pentasaccharide resembling the glycosaminoglycan-core protein
linkage region. Here we show that human melanoma M21 cells and human
neuroblastoma cells incubated with Xylbeta-MU/pNP also make an alpha-GalNAc
terminated heptasaccharide containing one chondroitin disaccharide repeat. High
performance liquid chromatography and matrix-assisted laser desorption ionization
mass spectrometry analysis of intact or glycosidase-digested xyloside showed the
structure as: GalNAcalphaGlcAbeta1,3GalNAcbeta1,4GlcAbeta1,3Galbe ta1,3Galbeta1,
4Xylbeta-MU/pNP. The alpha-GalNAc-terminated xylosides can account for
approximately 10% of the total Xylbeta-MU/pNP products ( approximately 1.5
nmol/h/mg). These results show that GalNAcalphaGlcAbeta-modification is
relatively abundant, but not unique to the GAG-linkage tetrasaccharide. alpha
GalNAc addition to the GlcA residue does not appear to be an extension of general
phase II detoxification of xenobiotics that involve glucuronidation, since M21
cells incubated with MU synthesize only 0.3 pmol GlcAbeta-MU/h/mg protein, and
undetectable amount of GalNAcalphaGlcAbeta-MU (<40 fmol/h/mg). Further,
subcellular fractionation shows that the alpha- N-
acetylgalactosaminyltransferase activity colocalizes in the Golgi with other
glycosyl transferases and not in the ER, where xenobiotic detoxification
glucuronosyltransferases are found. Although GalNAcalphaGlcAbeta-terminal
modification has not been detected on naturally occurring GAG chains, the
substantial amount of alpha-GalNAc transferase activity suggests that the alpha
GalNAc transferase could utilize other GlcA-containing glycoconjugates as
acceptors.
PMID- 9639543
TI - A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells
regulates their proliferation and migration.
AB - The formation of atherosclerotic lesions is characterized by invasion of vascular
smooth muscle cells (VSMC) into the tunica intima of the arterial wall and
subsequently by increased proliferation of VSMC, a process apparently restricted
to the intimal layer of blood vessels. Both events are preceded by the
pathological overexpression of several growth factors, such as platelet-derived
growth factor (PDGF) which is a potent mitogen for VSMC and can induce their
chemotaxis. PDGF is generally not expressed in the normal artery but it is
upregulated in atherosclerotic lesions. We have previously shown that PDGF-BB
specifically stimulates proliferating VSMC to secrete a 340 kDa hyaluronic acid
(HA-340). Here, we present evidence regarding the biological functions of this
glycan. We observed that HA-340 inhibited the PDGF-induced proliferation of human
VSMC in a dose-dependent manner and enhanced the PDGF-dependent invasion of VSMC
through a basement membrane barrier. These effects were abolished following
treatment of HA-340 with hyaluronidase. The effect of HA-340 on the PDGF
dependent invasion of VSMC coincided with increased secretion of the 72-kDa type
IV collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid
inhibitor of matrix metalloproteinases. HA-340 did not exert any chemotactic
potency, nor did it affect chemotaxis of VSMC along a PDGF gradient. In human
atheromatic aortas, we found that HA-340 is expressed with a negative
concentration gradient from the tunica media to the tunica intima and the
atheromatic plaque. Our findings suggest that HA-340 may be linked to the
pathogenesis of atherosclerosis, by modulating VSMC proliferation and invasion.
PMID- 9639544
TI - Two soluble glycosyltransferases glycosylate less efficiently in vivo than their
membrane bound counterparts.
AB - Many Golgi glycosyltransferases are type II membrane proteins which are cleaved
to produce soluble forms that are released from cells. Cho and Cummings recently
reported that a soluble form of alpha1, 3-galactosyltransferase was comparable to
its membrane bound counterpart in its ability to galactosylate newly synthesized
glycoproteins (Cho,S.K. and Cummings,R.D. (1997) J. Biol. Chem., 272, 13622
13628). To test the generality of their findings, we compared the activities of
the full length and soluble forms of two such glycosyltransferases, ss1,4 N
Acetylgalactosaminyltransferase (GM2/GD2/ GA2 synthase; GalNAcT) and beta
galactoside alpha2,6 sialyltransferase (alpha2,6-ST; ST6Gal I), for production of
their glycoconjugate products in vivo . Unlike the full length form of GalNAcT
which produced ganglioside GM2 in transfected cells, soluble GalNAcT did not
produce detectable GM2 in vivo even though it possessed in vitro GalNAcT activity
comparable to that of full length GalNAcT. When compared with cells expressing
full length alpha2,6-ST, cells expressing a soluble form of alpha2,6-ST contained
3-fold higher alpha2,6-ST mRNA levels and secreted 7-fold greater alpha2,6-ST
activity as measured in vitro , but in striking contrast contained 2- to 4-fold
less of the alpha2,6-linked sialic acid moiety in cellular glycoproteins in vivo
. In summary these results suggest that unlike alpha1,3-galactosyltransferase the
soluble forms of these two glycosyltransferases are less efficient at
glycosylation of membrane proteins and lipids in vivo than their membrane bound
counterparts.
PMID- 9639545
TI - Microneurographic research on sympathetic nerve responses to environmental
stimuli in humans.
AB - The sympathetic nervous system plays an important role to maintain the
homeostasis of vital functions in humans against environmental stimuli.
Sympathetic nerve responses to environmental stimuli in humans have been assessed
conventionally using rather indirect methods by analyzing the responses of
effector organs or by measuring the changes in plasma norepinephrine level.
Meanwhile, the microneurography technique has enabled us to approach the
sympathetic nervous system in humans more directly. By applying this technique,
it has become possible to investigate how the human sympathetic nervous system
responds to different kinds of environmental stimuli. In this paper, the
usefulness of microneurography as a research tool in environmental physiology is
shown together with a review of microneurographic findings on sympathetic nerve
responses to environmental stimuli in humans.
PMID- 9639546
TI - Force-velocity relation of sliding of skeletal muscle myosin, arranged on a
paramyosin filament, on actin cables.
AB - To investigate in vitro ATP-dependent sliding of regularly arranged myosin
molecules on actin filaments, we prepared thick hybrid filaments in which myosin
molecules isolated from rabbit skeletal muscle were arranged around the
paramyosin core (length, 10-20 micron; diameter, =0.2 micron) obtained from a
molluscan smooth muscle. A single to a few thick hybrid filaments were attached
to a polystyrene bead (diameter, 4.5 micron; specific gravity, 1.5) and made to
slide on actin filament arrays (actin cables) in the internodal cell of an alga,
mounted on the rotor of a centrifuge microscope. The bead was subjected to
centrifugal forces serving as external loads to the ATP-dependent actin-myosin
sliding. The maximum unloaded sliding velocity of the thick filament attached
bead (mean, 3.4 micron/s; 20-23 degrees C) was significantly higher than that of
the bead coated with randomly oriented myosin molecules reported previously. The
steady-state force-velocity (P-V) relations obtained were qualitatively similar
to those in intact skeletal muscle fibers. These results indicate that this in
vitro motility assay system retains the basic characteristics of contracting
skeletal muscle fibers, and that it may be effectively used to study mechanisms
underlying the steady-state P-V characteristics of ATP-dependent actin-myosin
sliding using various recombinant myosins produced in nonmuscle cells.
PMID- 9639547
TI - Effects of Ca2+ and epinephrine on Ca2+ recirculation fraction and total Ca2+
handling in canine left ventricles.
AB - We investigated the effects of intracoronary Ca2+ and epinephrine on the
intracellular Ca2+ recirculation fraction (RF) and total Ca2+ handling in the
left ventricle (LV) of the excised cross-circulated canine heart preparation. We
analyzed LV postextrasystolic potentiation (PESP) following a spontaneous
extrasystole that occurred sporadically under constant atrial pacing. All PESPs
decayed in alternans and none decayed monotonically. We extracted an exponential
decay component from the alternans PESP, determined its beat constant (taue), and
calculated RF = exp(-1/taue). Increased intracoronary Ca2+ slightly increased
taue and RF, but epinephrine did not change them, although both agents enhanced
LV contractility 2-3 times. Neither Ca2+ nor epinephrine affected the sinusoidal
decay of the alternans PESP. These results indicate that RF via the sarcoplasmic
reticulum was slightly augmented by Ca2+, but not by epinephrine. We combined
these RF data with LV Ca2+ handling O2 consumption data and obtained 40-110
micromol/kg as the total amount of Ca2+ handled in one cardiac cycle in the
control and enhanced contractile states. These results indicate that this new LV
level approach seems to better the understanding of the Ca2+ mass dynamics
responsible for the mechanoenergetics enhanced by inotropic interventions.
PMID- 9639548
TI - Basic fibroblast growth factor-mediated lymphangiogenesis of lymphatic
endothelial cells isolated from dog thoracic ducts: effects of heparin.
AB - We have attempted to evaluate whether, similar to the angiogenesis of blood
vessels, cultures of lymphatic endothelial cells (LEC) isolated from dog thoracic
ducts have an ability to induce lymphangiogenesis in response to basic fibroblast
growth factor (bFGF), then to examine the effects of heparin on the bFGF-mediated
morphogenesis. The effects of bFGF and/or heparin on the proliferation and
migration of the LEC were evaluated by changing the number of the subconfluent
cells and by wound migration assay, respectively. The effects of the agents on
invasion and tube formation of the LEC into a three-dimensional collagen gel and
on collagen gel induced tube formation of the LEC were also investigated by a
phase-contrast microscope and an electron microscope. The bFGF (10 ng/ml) caused
a significant induction of proliferation and migration of the LEC, the induction
of which was augmented dose-dependently by an additional treatment with heparin
ranging from 1 to 100 microg/ml. The bFGF produced invasion and tube formation of
the LEC into a three-dimensional collagen gel. The bFGF also facilitated to form
capillary-like tubes of the LEC between two layers of collagen gels. Heparin (10
microg/ml) accelerated both processes of bFGF-mediated lymphangiogenesis of the
LEC. These findings suggest that the cultured LEC isolated from dog thoracic
ducts have an ability to form lymphatic capillary-like tubes in response to bFGF
and that heparin accelerates dose-dependently the process of the bFGF-mediated
neovascularization of lymph vessels.
PMID- 9639549
TI - Nonshivering thermoregulatory responses in trained athletes: effects of physical
fitness and body fat.
AB - We studied the difference of thermoregulatory responses between trained male
athletes (TR, n = 9) and untrained men (UT, n = 7) during 60 min of cold exposure
(15 degrees C) without shivering, and examined the effects of physical fitness
and body fat on these responses. Mean skin temperature (Tsk), esophageal
temperature (Tes), and skin conductance (Kb) were similar between TR and UT, and
heat production (M) for TR increased significantly during exposure at 15 degrees
C. The M at 15 degrees C correlated positively with maximal oxygen uptake and
negatively with body fat (%BF), but not with Tes. The Kb correlated negatively
with Tes and positively with Tsk. The %BF also correlated negatively with Kb and
Tsk during exposure at 15 degrees C, and the slope of %BF vs. Tsk relationship
was significantly steeper in TR than in UT. These results suggest that (1) body
temperature is maintained by the reduction of skin conductance, and (2) heat
insulation independent of body fat is enhanced in trained athletes during cold
exposure without shivering.
PMID- 9639550
TI - Effects of different types of clothing on circadian rhythms of core temperature
and urinary catecholamines.
AB - This study investigated the effects of three different types of clothing on the
circadian rhythms of core temperature and urinary catecholamines. One type of
clothing consisted of long-sleeved shirts, full-length trousers, and socks (Type
L, 1,042 g); the second type was of half-sleeved shirts and knee-length trousers
(Type H, 747 g); the third type was of Type H during the daytime and Type L
during night sleep (Type M). Six healthy females participated in this study where
rectal temperature, skin temperatures, heart rate, and urinary catecholamines
were continuously measured for 37.5 h at an ambient temperature of 23.8 +/- 0.2
degrees C and a relative humidity of 60 +/- 5%. The results were as follows: (1)
The nocturnal minimum of rectal temperature decreased significantly in the
sequence Type L < Type M < Type H clothing, and 27.2 and 12.4% of the circadian
amplitude were influenced by type of clothing during the daytime and the
nighttime, respectively. (2) The rise of skin temperatures in the extremities
increased significantly more after the subjects retired for sleep with Type M or
Type H clothing than with Type L. (3) Urinary catecholamines decreased more in
the evening and increased more in the morning with Type H and Type M clothing
than with Type L. These results show that the circadian rhythm of core
temperature, especially the nocturnal minimum value, was influenced by the type
of clothing worn not only during the nighttime, but also during the daytime.
PMID- 9639551
TI - Role of platelet-activating factor on extravascular lung water after coronary
reperfusion in dogs.
AB - Platelet-activating factor (PAF), one of the harmful substances released after
coronary reperfusion, has been reported to increase pulmonary vascular
permeability and induce pulmonary edema. In this study, we sought to examine the
possible role of PAF in the genesis of pulmonary edema after coronary
reperfusion. Extravascular lung water (EVLW) was measured by the thermal-dye
double indicator dilution method during coronary ligation and after reperfusion
in situ in dogs. The proximal left anterior descending coronary artery was
occluded for 15 min and reperfused in 5 dogs (group 1), while five other dogs
(group 2) were treated with PAF-antagonist (TCV-309, 1 mg/kg) before coronary
artery occlusion. EVLW and hemodynamic indices were measured at baseline, 15 min
of coronary occlusion, and 15 and 30 min after coronary reperfusion. EVLW
increased at 15 min of coronary occlusion in both groups, but there was no
significant difference between the two groups (6.4 to 10.3 ml/kg and 5.4 to 7.1
ml/kg in groups 1 and 2, respectively). After coronary reperfusion, EVLW
increased further in group 1 (6.4 to 16.5 ml/kg, p < 0.01), but no further
increase was observed in group 2 at 30 min after coronary reperfusion. There were
no significant differences in hemodynamic indices between the two groups
throughout the test. Thus, PAF-antagonist attenuated the increase in EVLW after
coronary reperfusion independent of hemodynamic indices, and hence, PAF may play
an important role in the genesis of pulmonary edema caused by coronary
reperfusion.
PMID- 9639552
TI - Changes in core temperature and thermoeffector thresholds in exercise-trained
rats.
AB - Spontaneous running in a running wheel has emerged as an alternative method of
exercise in small animals. The present study investigated how exercise training
with a running wheel affects core temperature level and thermoeffector thresholds
in rats. Female rats were allowed to run freely in the wheel for 6 months.
Sedentary controls did not exercise during the same period. After the exercise
training period, they were loosely restrained and their threshold core
temperatures for tail skin vasodilation and cold-induced thermogenesis were
determined by warming or cooling the animals by use of a chronically implanted
intravenous thermode. Resting and threshold core temperatures of the exercise
trained rats were higher than those of the sedentary controls. The results
suggest that in rat, exercise training with a running wheel shifts threshold
temperatures for heat loss and heat production to high levels, which may result
in a rise in core temperature level.
PMID- 9639553
TI - Plasma insulin and growth hormone during antarctic residence.
AB - Circulatory levels of insulin and growth hormone (GH) were estimated in nine
tropical euglycemic men in New Delhi and during the first week of every month of
stay in Dakshin Gangotri, Antarctica. Prolonged residency in Antarctica did not
alter GH levels because mean GH values during Austral summer and Austral winter
were not significantly different from the New Delhi values. Compared with GH, the
insulin levels during March, April, and June were found to be significantly lower
than the New Delhi values. In Antarctica, the insulin levels in March, April,
May, June, July, and August were also found to be significantly lower than the
December values. This decline in insulin in Antarctica might be important in
increasing substrate availability for heat production by facilitating lipolysis
and hepatic glucose output.
PMID- 9639554
TI - Prothymosin alpha is a chromatin-remodelling protein in mammalian cells.
AB - Prothymosin alpha (ProTalpha) is an abundant mammalian acidic nuclear protein
whose expression is related to cell proliferation. Here we report that in HL-60
cells overexpressing ProTalpha, the accessibility of micrococcal nuclease to
chromatin is strongly increased. In the DNA ladder generated by the nuclease
activity, the sizes of the mononucleosome (146 bp, the DNA fragment that is bound
to the histone octamer) and its multimers correspond to nucleosomes lacking
histone H1. The percentage of histone-H1-depleted chromatin (active chromatin) is
also higher in the cells overexpressing ProTalpha. On the basis of these and
previous findings, we propose a biological role for ProTalpha in the remodelling
of chromatin fibres through its interaction with histone H1.
PMID- 9639555
TI - The majority of human glutathione peroxidase type 5 (GPX5) transcripts are
incorrectly spliced: implications for the role of GPX5 in the male reproductive
tract.
AB - An epididymis-specific, secretory glutathione peroxidase (GPX5) has been proposed
previously to play a role in protecting mammalian sperm membranes from the
deleterious effects of lipid peroxidation, which, if not contained, can lead to
reduced fertilizing capacity. Here we report the cDNA cloning of human GPX5 and
show that the majority of transcripts contain a 118 nt frame-shifting deletion,
arising, most likely, from inappropriate excision of exon 3 during processing.
Antisera raised against recombinant human GPX5 cross-reacted with rat and macaque
(Macaca fascicularis) epididymal proteins of the size expected for full-length,
active GPX5. However, no similar reactivity could be demonstrated in any of the
human samples tested.
PMID- 9639556
TI - Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and
SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase
kinase (MKK) kinase-1.
AB - Overexpression of the protein kinases mixed-lineage kinase-2 (MLK2) or mitogen
activated protein kinase (MAPK) kinase kinase-1 (MEKK1) is known to trigger the
activation of stress-activated protein kinase (SAPK1)/c-Jun N-terminal kinase
(JNK). Here we demonstrate that MLK2 activates SAPK kinase-1 (SKK1)/MAPK kinase 4
(MKK4) and SKK4/MKK7, the two known direct activators of SAPK1/JNK (both in
transfection studies and in vitro). In contrast, MEKK1 activates SKK1/MKK4 more
efficiently than MLK2, but barely activates SKK4/MKK7. Since SKK4/MKK7 (but not
SKK1/MKK4) is activated by interleukin-1 and tumour necrosis factor in several
cells and tissues, we suggest that MEKK1 does not mediate the activation of
SKK4/MKK7 and SAPK1/JNK induced by these pro-inflammatory cytokines. MLK2 and
MEKK1 also activated SKK2/MKK3 and SKK3/MKK6, the direct upstream activators of
SAPK2a/p38.
PMID- 9639557
TI - Elucidation of a promoter activity that directs the expression of acetyl-CoA
carboxylase alpha with an alternative N-terminus in a tissue-restricted fashion.
AB - Previous studies in rats and humans have demonstrated that acetyl-CoA carboxylase
alpha (ACC-alpha), the principal ACC isoenzyme in lipogenic tissues, is
transcribed from two promoters, PI and PII, that operate in a tissue-specific
fashion. Each promoter gives rise to ACC-alpha mRNA isoforms that differ in their
5' untranslated regions but essentially encode the same protein product. In the
present study we demonstrate that such a pattern of promoter usage is evident in
sheep tissues but in addition we have detected the expression of a novel ACC
alpha mRNA isoform that is expressed in a variety of tissues including kidney,
lung, liver and mammary gland, where it is markedly induced during lactation.
This novel transcript differs from the previously described ACC-alpha mRNA in
that exon 5, the primary coding exon in both PI and PII transcripts, is replaced
by a 424-nt sequence that seems to represent the 5' terminus of the mRNA. The 424
nt sequence encodes a 17-residue N-terminal region as the N-terminal residue in
the deduced sequence is a methionine flanked by several in-frame stop codons. The
5' terminal 424 nt are present as a single exon, which we have termed exon 5A, in
the sheep ACC-alpha gene and this is located approx. 15 kb downstream of exon 5
and 5 kb upstream of exon 6. A 1.5 kb HindIII-BglII fragment encompassing the 5'
terminus and sequence immediately upstream of exon 5A demonstrates promoter
activity when transiently transfected into HepG2 cells and HC11 mouse mammary
cells and this is markedly enhanced when insulin is present in the culture
medium. Promoter activity is also evident in primary sheep mammary epithelial
cells. These results demonstrate the presence of a third promoter, PIII, in the
ACC-alpha gene that results in the tissue-restricted expression of an ACC
isoenzyme.
PMID- 9639558
TI - Functional characterization of a recombinant form of the C-terminal, globular
head region of the B-chain of human serum complement protein, C1q.
AB - The first step in the activation of the classical pathway of the complement
system by immune complexes involves the binding of the six globular heads of C1q
to the Fc regions of IgG or IgM. The globular heads of C1q are located C-terminal
to the six triple-helical stalks present in the molecule; each head is considered
to be composed of the C-terminal halves (3x136 residues) of one A-, one B- and
one C-chain. It is not known if the C-terminal globular regions, present in each
of the three types of chain, are independently folded modules (with each chain
having distinct binding properties towards immunoglobulins) or whether the
different binding functions of C1q are dependent upon a globular structure which
relies on contributions from all three chains. As a first step towards addressing
this question, we have expressed the globular head region (residues 87-226) of
the C1q B-chain (ghB) as a soluble fusion protein with maltose-binding protein
(MBP) in Escherichia coli. The affinity purified fusion protein, designated MBP
ghB, behaved as a dimer on gel filtration and bound preferentially to aggregated
IgG rather than to IgM. It could also inhibit C1q-dependent haemolysis of both
IgG- and IgM-sensitized erythrocytes. After its release from MBP, by use of
Factor Xa, the free ghB exhibited a tendency to aggregate and come out of
solution. Since MBP is known to be a monomeric molecule, the dimerization of the
MBP-ghB fusion polypeptide is probably brought about by the ghB region, perhaps
through hydrophobic interactions within the ghB region. The functional behaviour
of MBP-ghB indicates that the globular regions of C1q may adopt a modular
organization, i.e. each globular head of C1q may be composed of three
structurally and functionally independent domains, thus retaining multivalency in
the form of a heterotrimer.
PMID- 9639559
TI - Characterization of authentic recombinant pea-seed lipoxygenases with distinct
properties and reaction mechanisms.
AB - The two major isoforms of lipoxygenase (LOX-2 and LOX-3) from pea (Pisum sativum
L. cv. Birte) seeds have been cloned and expressed from full-length cDNAs as
soluble, active, non-fusion proteins in Escherichia coli. A comparison of both
isoforms purified to apparent homogeneity from E. coli and pea seeds has
confirmed the authenticity of the recombinant products and established the
properties of the native enzymes. Despite 86% similarity at the amino acid
sequence level, the enzymes have distinct properties. They have been
characterized in terms of specific activity, Fe content, optimum pH, substrate
and product specificity, apparent Km and Vmax for the preferred substrate,
linoleic acid, and interfacial behaviour with linoleic acid. We have used this
evidence, in addition to EPR spectroscopy of the hydroperoxide-activated enzymes
and estimates of kcat/Km, to propose different reaction mechanisms for linoleic
acid oxidation for the two isoforms. The differences relate primarily to carbonyl
production from linoleic acid for which we propose a mechanism. This implicates
the release of a peroxyl radical in an aerobic hydroperoxidase reaction, as the
source of the carbonyl compounds formed by dismutation of the liberated peroxyl
radical.
PMID- 9639560
TI - Cytotoxic effect of HIV-1 coat glycoprotein gp120 on human neuroblastoma CHP100
cells involves activation of the arachidonate cascade.
AB - HIV type-1 (HIV-1) coat glycoprotein gp120 causes necrotic death in human
neuroblastoma CHP100 cells. Here, we investigated the possible role of the
arachidonate cascade and membrane peroxidation in gp120-induced cell necrosis. It
is shown that gp120 increases the intracellular concentrations of prostaglandin
E2 and leukotriene B4 by up-regulating the activity and expression of the
arachidonate-metabolizing enzymes prostaglandin H synthase and 5-lipoxygenase
respectively. Consistent with this observation, selective inhibitors of
prostaglandin H synthase (i.e. indomethacin) and 5-lipoxygenase (i.e. MK886 and
caffeic acid) protected CHP100 cells against gp120-induced necrosis. Treatment
with gp120 also enhanced membrane lipid peroxidation and this may be implicated
in the execution of cell damage. Interestingly, incubation with exogenous nitric
oxide (NO) mimicked the effects of gp120 on necrotic death of CHP100 cells and
activation of prostaglandin H synthase and 5-lipoxygenase. This suggests that NO
might participate in the mechanism by which gp120 activates the arachidonate
cascade.
PMID- 9639561
TI - The first high-mobility-group box of upstream binding factor assembles across
over DNA junction by basic residues.
AB - Upstream binding factor (UBF) is a eukaryotic RNA polymerase I-specific
transcription factor. Its predominant DNA-binding motif, ubfHMG box 1, preserves
DNA assembling activity that can bind two or more DNA duplexes simultaneously to
form a crossover DNA junction. Here we investigate the basis of crossover DNA
assembling activity of ubfHMG box 1 by extensive mutagenesis analyses and
mobility shift assay. Although the ubfHMG box 1 preserves a high mobility group
(HMG) core structure, changing a number of the consensus hydrophobic and aromatic
residues to alanine did not inhibit its crossover-assembling activity. This
indicates that these residues do not directly participate in protein-DNA
interaction. However, altering a series of basic residues in the helices 1 and 2
regions or the N-terminal extended strand of the ubfHMG box 1 motif had severe
effects on DNA-assembling activity; however, certain non-specific DNA binding
activity still remained. This suggests that the ubfHMG box 1 motif might
extensively contact the backbone of a crossover junction through its multiple
basic residues. Mutating a hydrophobic residue in the terminal dimerization
domain inhibited the association of truncated Xenopus UBF, but had little effect
on its crossover-assembling activity. This indicates that the UBF-crossover DNA
complex is not established by the association of individual DNA-bound peptides.
PMID- 9639562
TI - Differential effects of phorbol ester on growth and protein kinase C isoenzyme
regulation in human hepatoma Hep3B cells.
AB - PMA has both mitogenic and antiproliferative effects on human hepatoma Hep3B
cells. In response to low PMA concentration (10 nM), Hep3B cells displayed an
increasing proliferation potentiation. At high PMA concentration (1 microM) Hep3B
cells exhibited modest cytostatic effects. Determinations of protein kinase C
(PKC) activity in PMA-treated cells revealed that alterations in PKC activity are
associated with proliferative capacity. The decrease in PKC activity mediated by
a high dose of PMA was accompanied by cell growth inhibition. Increases in PKC
activity mediated by a low dose of PMA were consistent with proliferation
stimulation. Immunoblot analysis showed that there are at least six PKC
isoenzymes: alpha, delta, epsilon, mu, zeta and iota/lambda, constitutively
expressed in Hep3B cells. Cellular fractionation and immunocytochemical staining
results demonstrated that both 10 nM and 1 microM PMA treatments induced a marked
translocation of PKC-alpha from cytosol to membrane or nuclear fraction within 5
30 min. At the same time PKC-delta and epsilon were translocated from the
membrane to nuclear fraction. In addition, prolonged treatment with 1 microM PMA,
but not with 10 nM PMA, selectively mediated the down-regulation of these three
PKC isoenzymes. The distinct effects of different concentrations of PMA on cell
proliferation and PKC-alpha, delta and epsilon isoenzyme modulation support the
involvement of these three PKC isotypes in the mechanism of action of Hep3B cells
in cell growth events.
PMID- 9639563
TI - Changing nucleosome positions in vivo through modification of the DNA rotational
information.
AB - The effects of the rotational information of DNA in determining the in vivo
localization of nucleosomal core particles (ncps) have been studied in the
Saccharomyces cerevisiae 5 S rRNA repeat gene. The distribution of the phased
series of flexibility signals present in this DNA has been altered by inserting
in its centre a 25 bp tract. The effects of such alteration on the in vivo
distribution of the helically phased, alternatively located ncps have been
determined relative to a reference 21 bp insertion mutant. The results show that
the answers provided in vitro and in vivo by the yeast 5 S rRNA gene sequence to
specific modifications of the DNA rotational frame are similar, thus pointing to
the relevance of DNA rotational information in vivo.
PMID- 9639564
TI - Structural and functional effect of Trp-62-->Gly and Asp-101-->Gly substitutions
on substrate-binding modes of mutant hen egg-white lysozymes.
AB - In order to clarify the structural role of subsite B of hen egg-white lysozyme in
hydrolytic activity towards a carbohydrate substrate, we analysed the structures
of Trp-62-->Gly and Asp-101-->Gly mutant hen lysozymes, which have no side chain
at positions 62 or 101, complexed with a substrate analogue, (N-acetyl-d
glucosamine)3 [(GlcNAc)3], using X-ray crystallography. The overall protein
structures in the mutant lysozyme complexes were almost identical to those in the
wild type. In the crystals of all the mutant complexes, the (GlcNAc)3 molecule,
which is an inhibitor of wild-type lysozyme, had no inhibitory effect, but was
hydrolysed as a substrate. One of the products, (GlcNAc)2, the reducing end of
which is an alpha-anomer, was bound in an unproductive binding mode, protruding
from the active-site cleft, and was able to act as an inhibitor. Hydrolysis of
the synthetic substrate by the mutants occurred in a beta-anomer-retaining
manner, and so the alpha-anomer product was converted from the beta-anomer
product. Thus the interactions of Asp-101 and Trp-62 in subsite B are not
essential for the catalytic mechanism, but co-operatively enhance the affinity of
the substrate in the productive binding mode, other than the inhibitor in the
unproductive mode.
PMID- 9639565
TI - Nuclear factor 1 regulates the distal silencer of the human PIT1/GHF1 gene.
AB - Here we report the characterization of 12 kb genomic DNA upstream of the human
PIT1/GHF1 promoter. Different regions involved in the modulation of human
PIT1/GHF1 gene expression were defined by transient transfection studies. Two
regions, one proximal (-7.1/-2. 3) and one distal (-11.8/-10.9), presented an
enhancer activity in pituitary cells when placed upstream of the SV40 promoter.
The 0.9 kb distal region was analysed further and found to decrease the basal
transcriptional activity of the human PIT1/GHF1 minimal promoter, indicating that
this region behaves as a silencer for its own promoter. Three Pit-1/GHF-1-binding
sites and two ubiquitous nuclear factor 1 (NF-1)-binding sites were identified by
DNase I footprinting in the distal regulatory region. Deletion analysis indicated
that NF-1 or NF-1-related protein(s) participate in the down-regulation of human
PIT1/GHF1 gene expression by interacting with an NF-1-binding site within the
distal regulatory region.
PMID- 9639566
TI - Alteration of zif268 zinc-finger motifs gives rise to non-native zinc-co
ordination sites but preserves wild-type DNA recognition.
AB - Zinc fingers are among the major structural motifs found in proteins that are
involved in eukaryotic gene regulation. Many of these zinc-finger domains are
involved in DNA binding. This study investigated whether the zinc-co-ordinating
(Cys)2(His)2 motif found in the three zinc fingers of zif268 could be replaced by
a (Cys)4 motif while still preserving DNA recognition. (Cys)2(His)2-to-(Cys)4
mutations were generated in each of the three zinc fingers of zif268
individually, as well as in fingers 1 and 3, and fingers 2 and 3 together.
Whereas finger 1 and finger 3 tolerate the switch, such an alteration in finger 2
renders the polypeptide incapable of DNA recognition. The protein-DNA interaction
was examined in greater detail by using a methylation-interference assay. The
mutant polypeptides containing the (Cys)4 motif in fingers 1 or 3 recognize DNA
in a manner identical to the wild-type protein, suggesting that the (Cys)4 motif
appears to give rise to a properly folded finger. Additional results indicate
that a zif268 variant containing a (Cys)2(His)(Ala) arrangement in finger 1 is
also capable of DNA recognition in a manner identical to the wild-type
polypeptide. This appears to be the first time that such alterations, in the
context of an intact DNA-binding domain, have still allowed for specific DNA
recognition. Taken together, the work presented here enhances our understanding
of the relationship between metal ligation and DNA-binding by zinc fingers.
PMID- 9639567
TI - The tumour necrosis factor-sensitive pool of sphingomyelin is resynthesized in a
distinct compartment of the plasma membrane.
AB - Sphingomyelin (SM) biosynthesis is believed to occur in the early Golgi
apparatus, plasma membrane and recycling endosomes. In the present study, the
localization of the SM synthesis that follows its hydrolysis upon activation of
the SM signal-transduction pathway was investigated in human skin fibroblasts
treated with tumour necrosis factor (TNF) alpha. After TNFalpha-induced
degradation, the intracellular SM levels returned to baseline levels within 30-60
min in cells treated at 37 degrees C. Pretreatment or co-incubation of cells with
bacterial sphingomyelinase or phospholipase C, decreasing the SM and
phosphatidylcholine content in the external leaflet of the plasma membrane
respectively, did not inhibit SM resynthesis. However, SM resynthesis was not
observed when TNFalpha-treated cells were continuously exposed to exogenous
sphingomyelinase, suggesting that under these particular conditions the
resynthesized SM becomes accessible to the enzyme. Furthermore, whereas
inhibition of vesicular traffic/endocytosis at 4 degrees C blocked exoplasmic SM
resynthesis, it did not alter SM resynthesis in TNFalpha-treated fibroblasts,
negating the role of endosomes and the Golgi apparatus. This was further
evidenced by the finding that after SM resynthesis, TNFalpha was again able to
promote SM turnover, even at 4 degrees C. In addition, when the exoplasmic
leaflet SM was hydrolysed by treating fibroblasts with bacterial
sphingomyelinase, resynthesis of SM occurred at 37 degrees C much more slowly
than after TNFalpha treatment. These findings support strongly the conclusion
that the SM, which is resynthesized after TNFalpha-induced hydrolysis, resides in
the cytosolic leaflet of the plasma membrane, and that the process involved in
this resynthesis displays characteristics different from those of the previously
described SM synthases.
PMID- 9639568
TI - Evidence that the conformation of unliganded human plasminogen is maintained via
an intramolecular interaction between the lysine-binding site of kringle 5 and
the N-terminal peptide.
AB - Human Glu-plasminogen adopts at least three conformations that provide a means
for regulating the specificity of its activation in vivo. It has been proposed
previously that the closed (alpha) conformation of human Glu-plasminogen is
maintained through physical interaction of the kringle 5 domain and a lysine
residue within the N-terminal peptide (NTP). To examine this hypothesis, site
directed mutagenesis was used to generate variant proteins containing
substitutions either for aspartic acid residues within the anionic centre of the
kringle 5 domain or for conserved lysine residues within the NTP. Size-exclusion
HPLC and rates of plasminogen activation by urokinase-type plasminogen activator
were used to determine the conformational states of these variants. Variants with
substitutions within the kringle 5 lysine-binding site demonstrated extended
conformations, as did variants with alanine substitutions for Lys50 and Lys62. In
contrast, molecules in which NTP residues Lys20 or Lys33 were replaced were shown
to adopt closed conformations. We conclude that the lysine-binding site of
kringle 5 is involved in maintaining the closed conformation of human Glu
plasminogen via an interaction with the NTP, probably through Lys50 and/or Lys62.
These conclusions advance the current model for the initial stages of
fibrinolysis during which fibrin is thought to compete with the NTP for the
kringle 5 lysine-binding site.
PMID- 9639569
TI - L-Mandelate dehydrogenase from Rhodotorula graminis: cloning, sequencing and
kinetic characterization of the recombinant enzyme and its independently
expressed flavin domain.
AB - The l-mandelate dehydrogenase (L-MDH) from the yeast Rhodotorula graminis is a
mitochondrial flavocytochrome b2 which catalyses the oxidation of mandelate to
phenylglyoxylate coupled with the reduction of cytochrome c. We have used the N
terminal sequence of the enzyme to isolate the gene encoding this enzyme using
the PCR. Comparison of the genomic sequence with the sequence of cDNA prepared by
reverse transcription PCR revealed the presence of 11 introns in the coding
region. The predicted amino acid sequence indicates a close relationship with the
flavocytochromes b2 from Saccharomyces cerevisiae and Hansenula anomala, with
about 40% identity to each. The sequence shows that a key residue for substrate
specificity in S. cerevisiae flavocytochrome b2, Leu-230, is replaced by Gly in L
MDH. This substitution is likely to play an important part in determining the
different substrate specificities of the two enzymes. We have developed an
expression system and purification protocol for recombinant L-MDH. In addition,
we have expressed and purified the flavin-containing domain of L-MDH
independently of its cytochrome domain. Detailed steady-state and pre-steady
state kinetic investigations of both L-MDH and its independently expressed flavin
domain have been carried out. These indicate that L-MDH is efficient with both
physiological (cytochrome c, kcat=225 s-1 at 25 degrees C) and artificial
(ferricyanide, kcat=550 s-1 at 25 degrees C) electron acceptors. Kinetic isotope
effects with [2-2H]mandelate indicate that H-C-2 bond cleavage contributes
somewhat to rate-limitation. However, the value of the isotope effect erodes
significantly as the catalytic cycle proceeds. Reduction potentials at 25 degrees
C were measured as -120 mV for the 2-electron reduction of the flavin and -10 mV
for the 1-electron reduction of the haem. The general trends seen in the kinetic
studies show marked similarities to those observed previously with the
flavocytochrome b2 (L-lactate dehydrogenase) from S. cerevisiae.
PMID- 9639570
TI - Re-design of Saccharomyces cerevisiae flavocytochrome b2: introduction of L
mandelate dehydrogenase activity.
AB - Flavocytochrome b2 from Saccharomyces cerevisiae is an l-lactate dehydrogenase
which exhibits only barely detectable activity levels towards another 2
hydroxyacid, l-mandelate. Using protein engineering methods we have altered the
active site of flavocytochrome b2 and successfully introduced substantial
mandelate dehydrogenase activity into the enzyme. Changes to Ala-198 and Leu-230
have significant effects on the ability of the enzyme to utilize l-mandelate as a
substrate. The double mutation of Ala-198-->Gly and Leu-230-->Ala results in an
enzyme with a kcat value (25 degrees C) with L-mandelate of 8.5 s-1, which
represents an increase of greater than 400-fold over the wild-type enzyme.
Perhaps more significantly, the mutant enzyme has a catalytic efficiency (as
judged by kcat/Km values) that is 6-fold higher with l-mandelate than it is with
L-lactate. Closer examination of the X-ray structure of S. cerevisiae
flavocytochrome b2 led us to conclude that one of the haem propionate groups
might interfere with the binding of L-mandelate at the active site of the enzyme.
To test this idea, the activity with l-mandelate of the independently expressed
flavodehydrogenase domain (FDH), was examined and found to be higher than that
seen with the wild-type enzyme. In addition, the double mutation of Ala-198-->Gly
and Leu-230-->Ala introduced into FDH produced the greatest mandelate
dehydrogenase activity increase, with a kcat value more than 700-fold greater
than that seen with the wild-type holoenzyme. In addition, the enzyme efficiency
(kcat/Km) of this mutant enzyme was more than 20-fold greater with L-mandelate
than with l-lactate. We have therefore succeeded in constructing an enzyme which
is now a better mandelate dehydrogenase than a lactate dehydrogenase.
PMID- 9639571
TI - Thrombin stimulates fibroblast procollagen production via proteolytic activation
of protease-activated receptor 1.
AB - Thrombin is a multifunctional serine protease that has a crucial role in blood
coagulation. It is also a potent mesenchymal cell mitogen and chemoattractant and
might therefore have an important role in the recruitment and local proliferation
of mesenchymal cells at sites of tissue injury. We hypothesized that thrombin
might also affect the deposition of connective tissue proteins at these sites by
directly stimulating fibroblast procollagen production. To address this
hypothesis, the effect of thrombin on procollagen production and gene expression
by human foetal lung fibroblasts was assessed over 48 h. Thrombin stimulated
procollagen production at concentrations of 1 nM and above, with maximal
increases of between 60% and 117% at 10 nM thrombin. These effects of thrombin
were, at least in part, due to increased steady-state levels of alpha1(I)
procollagen mRNA. They could furthermore be reproduced with thrombin receptor
activating peptides for the protease-activated receptor 1 (PAR-1) and were
completely abolished when thrombin was rendered proteolytically inactive with the
specific inhibitors d-Phe-Pro-ArgCH2Cl and hirudin, indicating that thrombin is
mediating these effects via the proteolytic activation of PAR-1. These results
suggest that thrombin might influence the deposition of connective tissue
proteins during normal wound healing and the development of tissue fibrosis by
stimulating fibroblast procollagen production.
PMID- 9639572
TI - Assembly of flammutoxin, a cytolytic protein from the edible mushroom Flammulina
velutipes, into a pore-forming ring-shaped oligomer on the target cell.
AB - Flammutoxin has been previously isolated as a cardiotoxic and cytolytic
polypeptide of 22 or 32 kDa from the fruiting bodies of the edible mushroom
Flammulina velutipes. In the present study, we purified flammutoxin as a single
haemolytic protein of 31 kDa and studied the mode of its cytolytic action. (1)
Flammutoxin caused efflux of potassium ions from human erythrocytes and swelling
of the cells before haemolysis. (2) Flammutoxin did not lyse human erythrocytes
in the presence of non-electrolytes with hydrodynamic diameters of >5.0 nm,
although it caused leakage of potassium ions and swelling of the cells under the
same conditions. (3) Experiments including solubilization of cell-bound toxin
with 2% (w/v) SDS at 20 degrees C and subsequent Western immunoblots showed that
flammutoxin formed a band corresponding to 180 kDa under the conditions where it
lysed erythrocytes. (4) Electron microscopy of flammutoxin-treated human
erythrocytes revealed the presence of a ring-shaped structure with outer and
inner diameters of 10 and 5 nm, respectively, on the cells. (5) A ring-shaped
toxin oligomer of the same dimensions was solubilized from the toxin-treated
human erythrocytes with 2% (w/v) SDS at 20 degrees C and isolated by a sucrose
gradient ultracentrifugation. These data indicated that flammutoxin assembles
into a ring-shaped oligomer possessing a hydrophilic pore of 4-5 nm on target
cells.
PMID- 9639573
TI - cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and
changes in rolipram inhibition triggered by protein kinase A phosphorylation of
Ser-54: generation of a molecular model.
AB - Ser-13 and Ser-54 were shown to provide the sole sites for the protein kinase A
(PKA)-mediated phosphorylation of the human cAMP-specific phosphodiesterase
isoform HSPDE4D3. The ability of PKA to phosphorylate and activate HSPDE4D3 was
mimicked by replacing Ser-54 with either of the negatively charged amino acids,
aspartate or glutamate, within the consensus motif of RRES54. The PDE4 selective
inhibitor rolipram ?4-[3-(cyclopentoxy)-4-methoxyphenyl]-2-pyrrolidone? inhibited
both PKA-phosphorylated HSPDE4D3 and the Ser-54-->Asp mutant, with an IC50 value
that was approximately 8-fold lower than that seen for the non-PKA-phosphorylated
enzyme. Lower IC50 values for inhibition by rolipram were seen for a wide range
of non-activated residue 54 mutants, except for those which had side-chains able
to serve as hydrogen-bond donors, namely the Ser-54-->Thr, Ser-54-->Tyr and Ser
54-->Cys mutants. The Glu-53-->Ala mutant exhibited an activity comparable with
that of the PKA phosphorylated native enzyme and the Ser-54-->Asp mutant but, in
contrast to the native enzyme, was insensitive to activation by PKA, despite
being more rapidly phosphorylated by this protein kinase. The activated Glu-53-
>Ala mutant exhibited a sensitivity to inhibition by rolipram which was unchanged
from that of the native enzyme. The double mutant, Arg-51-->Ala/Arg-52-->Ala,
showed no change in either enzyme activity or rolipram inhibition from the native
enzyme and was incapable of providing a substrate for PKA phosphorylation at Ser
54. No difference in inhibition by dipyridamole was seen for the native enzyme
and the Ser-54-->Asp and Ser-54-->Ala mutants. A model is proposed which
envisages that phosphorylation by PKA triggers at least two distinct
conformational changes in HSPDE4D3; one of these gives rise to enzyme activation
and another enhances sensitivity to inhibition by rolipram. Activation of
HSPDE4D3 by PKA-mediated phosphorylation is suggested to involve disruption of an
ion-pair interaction involving the negatively charged Glu-53. The increase in
susceptibility to inhibition by rolipram upon PKA-mediated phosphorylation is
suggested to involve the disruption of a hydrogen-bond involving the side-chain
hydroxy group of Ser-54.
PMID- 9639574
TI - Targeting and assembly of the oxoglutarate carrier: general principles for
biogenesis of carrier proteins of the mitochondrial inner membrane.
AB - We have studied the targeting and assembly of the 2-oxoglutarate carrier (OGC),
an integral inner-membrane protein of mitochondria. The precursor of OGC,
synthesized without a cleavable presequence, is transported into mitochondria in
an ATP- and membrane potential-dependent manner. Import of the mammalian OGC
occurs efficiently into both mammalian and yeast mitochondria. Targeting of OGC
reveals a clear dependence on the mitochondrial surface receptor Tom70 (the 70
kDa subunit of the translocase of the outer mitochondrial membrane), whereas a
cleavable preprotein depends on Tom20 (the 20 kDa subunit), supporting a model of
specificity differences of the receptors and the existence of distinct targeting
pathways to mitochondria. The assembly of minute amounts of OGC imported in vitro
to the dimeric form can be monitored by blue native electrophoresis of digitonin
lysed mitochondria. The assembly of mammalian OGC and fungal ADP/ATP carrier
occurs with high efficiency in both mammalian and yeast mitochondria. These
findings indicate a dynamic behaviour of the carrier dimers in the mitochondrial
inner membrane and suggest a high conservation of the assembly reactions from
mammals to fungi.
PMID- 9639575
TI - Membrane type 1 matrix metalloproteinase (MT1-MMP) cleaves the recombinant
aggrecan substrate rAgg1mut at the 'aggrecanase' and the MMP sites.
Characterization of MT1-MMP catabolic activities on the interglobular domain of
aggrecan.
AB - The recent detection of membrane type 1 matrix metalloproteinase (MT1-MMP)
expression in human articular cartilage [Buttner, Chubinskaya, Margerie, Huch,
Flechtenmacher, Cole, Kuettner, and Bartnik (1997) Arthritis Rheum. 40, 704-709]
prompted our investigation of MT1-MMP's catabolic activity within the
interglobular domain of aggrecan. For these studies we used rAgg1mut, a mutated
form of the recombinant fusion protein (rAgg1) that has been used as a substrate
to monitor 'aggrecanase' catabolism in vitro [Hughes, Buttner, Eidenmuller,
Caterson and Bartnik (1997) J. Biol. Chem. 272, 20269-20274]. The rAgg1 was
mutated (G332 to A) to avoid the generation of a splice variant seen with the
original genetic construct, which gave rise to heterogeneous glycoprotein
products. This mutation yielded a homogeneous recombinant product. Studies in
vitro with retinoic acid-stimulated rat chondrosarcoma cells indicated that the
rAgg1mut substrate was cleaved at the 'aggrecanase' site equivalent to Glu373
Ala374 (human aggrecan sequence enumeration) in its interglobular domain sequence
segment. The differential catabolic activities of the recombinant catalytic
domain (cd) of MT1-MMP and matrix metalloproteinases (MMPs) 3 and 8 were then
compared by using this rAgg1mut as a substrate. Coomassie staining of rAgg1mut
catabolites separated by SDS/PAGE showed similar patterns of degradation with all
three recombinant enzymes. However, comparative immunodetection analysis, with
neoepitope antibodies BC-3 (anti-ARGS...) and BC-14 (anti-FFGV...) to distinguish
between 'aggrecanase' and MMP-generated catabolites, indicated that the catalytic
domain of MT1-MMP exhibited strong 'aggrecanase' activity, cdMMP-8 weak activity
and cdMMP-3 no activity. In contrast, cdMMP-3 and cdMMP-8 led to strongly BC-14
reactive catabolic fragments, whereas cdMT1-MMP resulted in weak BC-14
reactivity. N-terminal sequence analyses of the catabolites confirmed these
results and also identified other potential minor cleavage sites within the
interglobular domain of aggrecan. These results indicate that MT1-MMP is yet
another candidate for 'aggrecanase' activity in vivo.
PMID- 9639576
TI - Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis
oocytes by changes in cytosolic pH.
AB - Several laboratories have investigated monocarboxylate transport in a variety of
cell types. The characterization of the cloned transporter isoforms in a suitable
expression system is nevertheless still lacking. H+/monocarboxylate co-transport
was therefore investigated in monocarboxylate transporter 1 (MCT1)-expressing
Xenopus laevis oocytes by using pH-sensitive microelectrodes and [14C]lactate.
Superfusion with lactate resulted in intracellular acidification of MCT1
expressing oocytes, but not in non-injected control oocytes. The basic kinetic
properties of lactate transport in MCT1-expressing oocytes were determined by
analysing the rates of intracellular pH changes under different conditions. The
results were in agreement with the known properties of the transporter, with
respect to both the dependence on the lactate concentration and the external pH
value. Besides lactate, MCT1 mediated the reversible transport of a wide variety
of monocarboxylic acids including pyruvate, D,L-3-hydroxybutyrate, acetoacetate,
alpha-oxoisohexanoate and alpha-oxoisovalerate, but not of dicarboxylic and
tricarboxylic acids. The inhibitor alpha-cyano-4-hydroxycinnamate bound strongly
to the transporter without being translocated, but could be displaced by the
addition of lactate. In addition to changes in the intracellular pH, lactate
transport also induced deviations from the resting membrane potential.
PMID- 9639577
TI - Effects of dietary Pi on the renal Na+-dependent Pi transporter NaPi-2 in
thyroparathyroidectomized rats.
AB - Dietary Pi and parathyroid hormone (PTH) are two most important physiological and
pathophysiological regulators of Pi re-absorption in the renal proximal tubule.
Effects of dietary Pi on Na+/Pi co-transporter NaPi-2 were investigated in
thyroparathyroidectomized (TPTX) rats. NaPi-2 protein and mRNA in the kidney
cortex of TPTX rats were increased approximately 3.8- and 2.4-fold in amount
respectively compared with those in the sham-operated animals. Administration of
PTH to the TPTX rats resulted in a decrease in the amount of NaPi-2 protein, but
not in the abundance of NaPi-2 mRNA. Deprivation of dietary Pi in the TPTX rats
did not affect the amount of NaPi-2 mRNA and protein. In the Pi-deprived TPTX
rats, feeding of a high-Pi diet resulted in marked decreases in Pi transport
activity and the amount of NaPi-2 protein in the superficial nephrons.
Immunohistochemical analysis demonstrated that administration of PTH to TPTX rats
resulted in a decrease in NaPi-2 immunoreactivity from both superficial and
juxtamedullary nephrons within 4 h. Switching TPTX animals from a low-Pi diet to
the high-Pi diet decreased NaPi-2 immunoreactivity from superficial nephrons, but
not from juxtamedullary nephrons, within 4 h. These results suggest that dietary
Pi could regulate the amount of NaPi-2 protein in the superficial nephrons in a
PTH-independent manner.
PMID- 9639578
TI - A structural comparison of the colicin immunity proteins Im7 and Im9 gives new
insights into the molecular determinants of immunity-protein specificity.
AB - We report the first detailed comparison of two immunity proteins which, in
conjunction with recent protein engineering data, begins to explain how these
structurally similar proteins are able to bind and inhibit the endonuclease
domain of colicin E9 (E9 DNase) with affinities that differ by 12 orders of
magnitude. In the present work, we have determined the X-ray structure of the
Escherichia coli colicin E7 immunity protein Im7 to 2.0 A resolution by molecular
replacement, using as a trial model the recently determined NMR solution
structure of Im9. Whereas the two proteins adopt similar four-helix structures,
subtle structural differences, in particular involving a conserved tyrosine
residue critical for E9 DNase binding, and the identity of key residues in the
specificity helix, lie at the heart of their markedly different ability to bind
the E9 DNase. Two other crystal structures were reported recently for Im7; in
one, Im7 was a monomer and was very similar to the structure reported here,
whereas in the other it was a dimer to which functional significance was
assigned. Since this previous work suggested that Im7 could exist either as a
monomer or a dimer, we used analytical ultracentrifugation to investigate this
question further. Under a variety of solution conditions, we found that Im7 only
ever exists in solution as a monomer, even up to protein concentrations of 15
mg/ml, casting doubt on the functional significance of the crystallographically
observed dimer. This work provides a structural framework with which we can
understand immunity-protein specificity, and in addition we believe it to be the
first successfully refined crystal structure solved by molecular replacement
using an NMR trial model with less than 100% sequence identity.
PMID- 9639579
TI - Secretory-granule dynamics visualized in vivo with a phogrin-green fluorescent
protein chimaera.
AB - To image the behaviour in real time of single secretory granules in
neuroendocrine cells we have expressed cDNA encoding a fusion construct between
the dense-core secretory-granule-membrane glycoprotein, phogrin (phosphatase on
the granule of insulinoma cells), and enhanced green fluorescent protein (EGFP).
Expressed in INS-1 beta-cells and pheochromocytoma PC12 cells, the chimaera was
localized efficiently (up to 95%) to dense-core secretory granules (diameter 200
1000 nm), identified by co-immunolocalization with anti-(pro-)insulin antibodies
in INS-1 cells and dopamine beta-hydroxylase in PC12 cells. Using laser-scanning
confocal microscopy and digital image analysis, we have used this chimaera to
monitor the effects of secretagogues on the dynamics of secretory granules in
single living cells. In unstimulated INS-1 beta-cells, granule movement was
confined to oscillatory movement (dithering) with period of oscillation 5-10 s
and mean displacement <1 microm. Both elevated glucose concentrations (30 mM),
and depolarization of the plasma membrane with K+, provoked large (5-10 microm)
saltatory excursions of granules across the cell, which were never observed in
cells maintained at low glucose concentration. By contrast, long excursions of
granules occurred in PC12 cells without stimulation, and occurred predominantly
from the cell body towards the cell periphery and neurite extensions. Purinergic
receptor activation with ATP provoked granule movement towards the membrane of
PC12 cells, resulting in the transfer of fluorescence to the plasma membrane
consistent with fusion of the granule and diffusion of the chimaera in the plasma
membrane. These results illustrate the potential use of phogrin-EGFP chimeras in
the study of secretory-granule dynamics, the regulation of granule-cytoskeletal
interactions and the trafficking of a granule-specific transmembrane protein
during the cycle of exocytosis and endocytosis.
PMID- 9639580
TI - Alteration of the isoform composition of plasma-membrane-associated rat sperm
alpha-L-fucosidase during late epididymal maturation: comparative
characterization of the acidic and neutral isoforms.
AB - In a previous study, evidence was provided for the presence of a novel plasma
membrane-associated neutral-pH-optimum alpha-L-fucosidase in rat sperm. In the
present study, rat sperm alpha-L-fucosidase was characterized during epididymal
maturation. The pH 7 activity optimum of alpha-L-fucosidase and its subunit
composition (one or two closely spaced immunoreactive protein bands of about 53+/
2 kDa) did not appear to change during transit through the epididymis.
Isoelectric focusing of alpha-L-fucosidase indicated the presence of a major
isoform (B) with a pI near 7 in sperm from testis, caput, corpus and the proximal
half of the cauda. alpha-L-Fucosidase from sperm from the distal half of the
cauda, which contained a significant enrichment of sperm and alpha-L-fucosidase
activity, contained isoform B and an additional minor isoform (A) with a pI near
5.2. Isoform B and small amounts of isoform A were present in sperm from the vas
deferens. The two fucosidase isoforms present in sperm from the distal cauda were
separated by isoelectric focusing and comparatively characterized. They had
similar pH-activity curves (with optima near pH 7) and comparable apparent KM
values (0.4+/-0.04 mM) for 4-methylumbelliferyl alpha-l-fucopyranoside.
Preincubation of the isoforms at different temperatures indicated that isoform A
is considerably more thermostable than isoform B. Immunoprecipitation studies
using polyclonal antibodies against human liver alpha-L-fucosidase indicated that
approx. 90% of the enzymic activity for both isoforms was immunoprecipitable
under conditions that immunoprecipitated essentially all the human liver enzyme.
Neuraminidase treatment of sperm alpha-L-fucosidase from distal cauda (when
compared with the appropriate heat-treated control) led to disappearance of
isoform A and a concomitant increase in isoform B. The overall results suggest
that isoform A is derived by sialylation of isoform B near the end of epididymal
maturation.
PMID- 9639581
TI - Sp3 regulates fas expression in lung epithelial cells.
AB - By transducing an apoptotic signal in immune effector cells, Fas has been
directly implicated in the control of immunological activity. Expression and
functional results, however, have also suggested a role for Fas in regulating
cell turnover in specific epithelial populations. To characterize factors
responsible for Fas expression in epithelial cells, approximately 3 kb of the 5'
flanking region of the mouse Fas gene was isolated. By rapid amplification of
cDNA ends and primer extension, transcriptional start sites were identified
within 50 bp upstream of the translation start site. Transient transfection of
promoter-luciferase constructs in a mouse lung epithelial cell line, MLE-15,
localized promoter activity to the first 77 bp of upstream sequence. By using a
60 bp DNA probe (-18 to -77) in electrophoretic mobility-shift assays, three
shifted complexes were found. Incubation with excess cold Sp1 oligonucleotide or
an anti-Sp3 antibody inhibited complex formation. Site-directed mutagenesis of
the Sp1 site resulted in 60-70% loss of promoter activity. In Drosophila SL-2
cells, promoter activity was markedly increased by co-transfection of an Sp3
expression construct. These results show that the Sp3 protein is involved in
regulating Fas gene expression in lung epithelial cells.
PMID- 9639583
TI - Identification of skatolyl hydroperoxide and its role in the peroxidase-catalysed
oxidation of indol-3-yl acetic acid.
AB - Indol-3-yl acetic acid (IAA, auxin) is a plant hormone whose degradation is a key
determinant of plant growth and development. The first evidence for skatolyl
hydroperoxide formation during the plant peroxidase-catalysed degradation of IAA
has been obtained by electrospray MS. Skatolyl hydroperoxide degrades
predominantly non-enzymically to oxindol-3-yl carbinol but in part enzymically
into indol-3-yl methanol via a peroxidase cycle in which IAA acts as an electron
donor. Skatolyl hydroperoxide is degradable by catalase. Horseradish peroxidase
isoenzyme C (HRP-C) and anionic tobacco peroxidase (TOP) exhibit differences in
their mechanisms of reaction. The insensitivity of the HRP-C-catalysed reaction
to catalase is ascribed to the formation of HRP-C Compound III at the initiation
step and its subsequent role in radical propagation. This is in contrast with the
TOP-catalysed process in which skatolyl hydroperoxide has a key role. Indol-3-yl
aldehyde is produced not via the peroxidase cycle but by catalysis involving
ferrous peroxidase. Because indol-3-yl aldehyde is one of the main IAA-derived
products identified in planta, we conclude that ferrous peroxidases participate
in IAA catalytic transformations in vivo. A general scheme for peroxidase
catalysed IAA oxidation is presented.
PMID- 9639582
TI - Ca2+ modulation of cis-unsaturated fatty acid-induced mutant protein kinase C
activity: indication of inhibitory Ca2+-binding site in protein kinase C-alpha.
AB - The C2 domain in protein kinase C (PKC) is homologous to equivalent domains in a
number of important cytoplasmic proteins. Except for its implied function in Ca2+
and phospholipid binding, the precise role of this domain is not well understood.
We examined the role of the C2 domain of PKC-alpha using a mutant enzyme in which
80% of this domain has been deleted. This mutant can be activated by phospholipid
and diacylglycerol, but is independent of Ca2+. In this regard, its
characteristics are similar to those of the novel PKCs (nPKCs), consistent with
the notion that the C2 domain of PKC confers its Ca2+ responsiveness. However,
when the C2 deletion mutant is activated by cis-unsaturated fatty acid, the
activity is strongly inhibited by Ca2+ at micromolar concentrations. The Ca2+
inhibition is dose-dependent and is specific to cis-unsaturated fatty acids. The
deletion mutant can also be activated synergistically by diacylglycerol and cis
fatty acid, but again activation is inhibited by Ca2+. Our results indicate that
a PKC lacking the C2 domain is Ca2+-responsive and there exists an additional
site for Ca2+ that modulates the sensitivity of the enzyme to cis-unsaturated
fatty acid but not to diacylglycerol. This modulatory Ca2+-binding site appears
to be suppressed by the C2 domain because the presence of the domain reverses the
direction of PKC activity induced by cis-unsaturated fatty acid. These results
suggest that the modulatory Ca2+-binding site could act as a molecular switch
selective for fatty acid activation by sensing the changes in the Ca2+ levels in
a cell, serving a possible mechanism of differential activation of cPKC with a C2
domain and nPKC lacking this domain.
PMID- 9639584
TI - The electroneutral cation-chloride cotransporters.
AB - Electroneutral cation-chloride cotransporters are widely expressed and perform a
variety of physiological roles. A novel gene family of five members, encompassing
a Na+-Cl- transporter, two Na+-K+-2Cl- transporters and two K+-Cl-
cotransporters, encodes these membrane proteins; homologous genes have also been
identified in a prokaryote and a number of lower eukaryotes. The cotransporter
proteins share a common predicted membrane topology, with twelve putative
transmembrane segments flanked by long hydrophilic N- and C-terminal cytoplasmic
domains. The molecular identification of these transporters has had a significant
impact on the study of their function, regulation and pathophysiology.
PMID- 9639585
TI - Relaxation and activation of graviresponses in Paramecium caudatum.
AB - The kinetics of gravitaxis and gravikinesis in Paramecium caudatum were
investigated by employing (1) step transitions from normal gravity (1 g) to
weightlessness (microgravity) and (2) turns of the experimental chambers from the
horizontal to the vertical position at 1 g. The transition to microgravity left
existing cell orientations unchanged. Relaxation of negative gravitaxis under
microgravity took longer than 10 s and may be described by the time constant of
the decay of orientation coefficients. Gravitaxis was started at 1 g by turning
the experimental chamber from a horizontal to a vertical position. Gravitaxis
activated rapidly during the turning procedure and relaxed to an intermediate
level after the turning had stopped. Gravity-induced regulation of swimming speed
(gravikinesis) at 1 g had reached a steady state after 1 min; at this point,
gravikinesis counteracted the effects of sedimentation (negative gravikinesis). A
step transition to microgravity initially reversed the sign of the gravikinesis
(positive gravikinesis). The relaxation of this kinetic response was not
completed during 10 s of microgravity. The data suggest that gravikinesis is
functionally unrelated to gravitaxis and is strongly affected by the rate of
change in acceleration. We present a model explaining why gravikinesis reverses
sign upon the onset of a step from 1 g to microgravity.
PMID- 9639586
TI - The electric image in weakly electric fish: physical images of resistive objects
in Gnathonemus petersii.
AB - The present study describes a measurement-based model of electric image
generation in the weakly electric mormyrid fish Gnathonemus petersii.
Measurements of skin impedance, internal resistivity and fish body dimensions
have been used to generate an electrical-equivalent model of the fish and to
calculate electrical images and equivalent dipole sources for elementary
resistive objects. These calculations allow us to understand how exafferent and
reafferent signals are sensed by electroreceptors. An object's electric image
consists of the modulation of the transcutaneous voltage profile generated by the
fish's own discharge. The results suggest a set of rules for electrolocation: (1)
the side of the fish where modulation is larger indicates the side on which the
object is situated; (2) the object's position in the electroreceptive field is
indicated by the point of maximum modulation of the transcutaneous voltage; (3)
the degree of focus of the image indicates the distance to the object. In
addition, center-surround opposition originating at pre-receptor level is
proposed. Both experimental measurements and modeling indicate that fish skin
impedance is relatively low (400-11 000 cm2) and
mainly resistive. This low skin impedance appears to enhance the local electric
organ discharge modulation, the center-surround effect, the signal-to-noise ratio
for electrolocation and the active space for electrocommunication.
PMID- 9639587
TI - A role of 5-HT2 receptors in the gill vasculature of the antarctic fish
Pagothenia borchgrevinki.
AB - This study was conducted to describe the cardiovascular responses to intra
arterial injections of serotonin in the Antarctic fish Pagothenia borchgrevinki
and to elucidate the underlying mechanisms. Immunohistochemistry was used to
localise serotonin-containing cells within the gills. Simultaneous and continuous
recordings of ventral and dorsal aortic blood pressure, heart rate and ventral
aortic blood flow (cardiac output) were made using standard cannulation
procedures in combination with Doppler flow measurement. An extracorporeal loop
with an in-line oxygen electrode allowed continuous measurements of arterial
oxygen pressure PaO2. Pre-branchial injection of serotonin (5-hydroxytryptamine,
5-HT) or the 5-HT2 receptor agonist alpha-methylserotonin increased the branchial
vascular resistance and ventral aortic pressure, while the 5-HT1 receptor agonist
piperazine was without effect. The branchial vasoconstriction produced by
serotonin injection was completely blocked by the 5-HT1/5-HT2 receptor antagonist
methysergide and the branchial vasoconstriction produced by WIDTH="9" HEIGHT="12"
ALIGN="BOTTOM" NATURALSIZEFLAG= alpha-methylserotonin injection was completely
blocked by the specific 5-HT2 receptor antagonist LY53857. The results suggest
that the 5-HT2 receptor alone mediates the branchial vasoconstriction. Serotonin
also mediated a methysergide-sensitive reduction in PaO2, the reduction being
greatest when the pre-injection PaO2 value was high. 5-HT-immunoreactive cells
and nerve fibres were present within the gill tissues. All the 5-HT
immunoreactive cells were located on the efferent side of the filaments, but 5-HT
immunoreactive nerve fibres were found lining both of the branchial arteries. Our
findings demonstrate a potential serotonergic control system for the gills in
Pagothenia borchgrevinki. In contrast to its effects on the branchial
vasculature, serotonin produced a methysergide-insensitive decrease in the
systemic vascular resistance. However, neither the specific 5-HT1 nor 5-HT2
receptor agonists produced a decrease in the resistance of the systemic
vasculature. The nature of the serotonergic receptor(s) inducing vasodilation in
teleost fish is uncertain.
PMID- 9639588
TI - Digging in sand crabs: coordination of joints in individual legs.
AB - Sand crabs use their multi-jointed legs to dig into sand. Combined movement and
electromyogram (EMG) analyses showed that the pattern of intra-leg coordination
in the legs of two sand crabs of different families (Blepharipoda occidentalis
and Emerita analoga) is similar in legs 2 and 3, but very different in leg 4. For
example, the sequence of proximal joint movements in legs 2 and 3 is elevation,
retraction, depression and protraction (similar to backward walking in most
decapods), but the sequence of proximal joint movements in leg 4 is elevation,
protraction, retraction and depression (similar to forward walking). The
synergies are the same during leg movements in sea water and in sand, suggesting
that the same motor programme is used in both situations. At the transition from
sea water into sand, however, both the frequency and amplitude of the EMG
potentials increase, and the phasing of the motor output to leg 2 (and presumably
leg 3) changes from proportional (both power and return strokes co-vary with
period) to return stroke constant (power strokes co-vary much more with period
than do return strokes). The motor output to leg 4 remains intermediate between
proportional and return stroke constant in sea water and in sand. On the basis of
the segmental specialisation of the motor patterns for the legs, we hypothesize
that sand crab digging may be an evolutionary mosaic of disparate ancestral
locomotor behaviours.
PMID- 9639589
TI - Burrow ventilation in the tube-dwelling shrimp Callianassa subterranea (Decapoda:
thalassinidea). I. Morphology and motion of the pleopods, uropods and telson.
AB - The morphology of the pleopods, uropods and telson of the tube-dwelling shrimp
Callianassa subterranea have been studied using dissection microscopy and
scanning electron microscopy. The kinematics of these appendages were examined by
motion analysis of macro-video recordings of ventilating shrimps in transparent
artificial burrows. The pleopods show the usual crustacean biramous anatomy, but
all segments are rostro-caudally flattened. The protopodite bears a triangular
medially oriented endopodite and a scoop-shaped exopodite. The contralateral
endopodites are linked by the appendix interna, ensuring a perfect phase
relationship between contralateral pleopods. The outer rims of the exopodites are
fringed with long fern-leaf-like plumose setae bearing flattened setules. These
setae have very mobile joints and can be turned caudally. The slits between
contralateral endopodites have rims of leaf-like setae as well. Setae of the same
leaf-like type fringe the uropods, but these are non-motile. The telson has a
narrow fringe of leaf-like setae, locally interrupted by long mechanoreceptory
setae. A shrimp, wandering through the burrow or resting, holds its pleopods
against the abdomen with the exopodites and their setal fringes retracted
medially. The uropods are folded medially as well, probably to reduce the
shrimp's drag. During ventilation, the uropods are extended against the tube
wall, leaving only a small opening for flow ventral from the telson, and the
pleopods beat at a frequency of approximately 1 Hz (0.9+/-0.2 Hz). Fourier
analysis of pleopod kinematics showed that the motion pattern of the first flow
generating pleopod pair (PP1) consisted mainly of the first harmonic (75 %) and
to a lesser extent of the third harmonic (20 %), resulting in almost perfect
sinusoidal motion. The motion patterns of PP2 and PP3 could be modelled by
assigning pure sinusoids with a 120 degrees phase shift and a rostro-caudal
ranking to the three pairs of pleopods.
PMID- 9639590
TI - Burrow ventilation in the tube-dwelling shrimp callianassa subterranea (Decapoda:
thalassinidea). II. The flow in the vicinity of the shrimp and the energetic
advantages of a laminar non-pulsating ventilation current.
AB - The ventilation flow in the vicinity of the pleopod-pumping thalassinid shrimp
Callianassa subterranea in an artificial transparent burrow has been mapped using
particle image velocimetry. The flow in the tube in front of the shrimp was
unidirectional, laminar and steady, with a parabolic cross-sectional velocity
profile. The mean flow velocity was 2.0+/-0.1 mm s-1. The flow passed the thorax
of the shrimp along the lateral and ventral sides. Ventral to the abdomen, the
flow was dominated by the metachronally oscillating pleopods. The water around a
pleopod is accelerated caudally and ventrally during the power stroke, and
decelerated to a much lesser extent during the recovery stroke owing to a
reduction in pleopod area. On average, the flow ventral to the abdomen converged
towards the small opening underneath the telson, simultaneously increasing in
velocity. A jet with a core velocity of 18-20 mm s-1 entered the area behind the
shrimp from underneath the telson. This caused a separation zone with backflow
caudal to the telson. Owing to the high rates of shear, the jet diverged and re
adjusted to a parabolic cross-sectional profile within 1-2 body lengths behind
the shrimp, showing no traces of pulsation. The metachronal pleopod movements in
combination with the increase in flow velocity at the constriction in the tube
caused by the uropods and the telson probably prevented pulsation. The energetic
consequences of pulsating and steady flows in combination with several tube
configurations were evaluated. The results suggested that, by constricting the
tube and keeping the flow steady, C. subterranea saves on ventilation costs by a
factor of up to six compared with oscillatory flow in a tube without the tail-fan
constriction.
PMID- 9639591
TI - Burrow ventilation in the tube-dwelling shimp Callianassa subterranea (Decapoda:
thalassinidea). III. Hydrodynamic modelling and the energetics of pleopod
pumping.
AB - The process of flow generation with metachronally beating pleopods in a tubiform
burrow was studied by designing a hydrodynamic model based on a thrust-drag force
balance. The drag of the tube (including the shrimp) comprises components for
accelerating the water into the tube entrance, for adjusting a parabolic velocity
profile, for accelerating the flow into a constriction due to the shrimp's body
and another constriction due to the extended tail-fan, for shear due to
separation and for the viscous resistance of all tube parts. The thrust produced
by the beating pleopods comprises components for the drag-based thrust and for
the added-mass-based thrust. The beating pleopods are approximated by oscillating
flat plates with a different area and camber during the power stroke and the
recovery stroke and with a phase shift between adjacent pleopod pairs. The added
mass is shed during the second half of the power stroke and is minimized during
the recovery stroke. A force balance between the pleopod thrust and the tube drag
is effected by calculating the mean thrust during one beat cycle at a certain
flow velocity in the tube and comparing it with the drag of the tube at that flow
velocity. The energetics of the tube and the pump are derived from the forces,
and the mechanical efficiency of the system is the ratio of these two. Adjusted
to standard Callianassa subterranea values, the model predicts a mean flow
velocity in the tube of 1.8 mm s-1. The mean thrust force, equalling the drag, is
36. 8 microN, the work done by the pleopod pump per beat cycle is 0.91 microJ and
the energy dissipated by the tube system is 0.066 microJ per cycle. The
mechanical efficiency is therefore 7.3 %. Pump characteristics that may be varied
by the shrimp are the beat frequency, the phase shift, the amplitude and the
difference in pleopod area between the power and recovery strokes. These
parameters are varied in the model to evaluate their effects. Furthermore, the
moment of added mass shedding, the distance between adjacent pleopods, the number
of pleopods and the total tube drag were also varied to evaluate their effects.
PMID- 9639592
TI - Prolonged swimming, recovery and repeat swimming performance of mature sockeye
salmon Oncorhynchus nerka exposed to moderate hypoxia and pentachlorophenol.
AB - Mature, wild sockeye salmon (Oncorhynchus nerka) demonstrated their remarkable
stamina and recovery abilities by performing three consecutive critical swimming
speed tests with only a 45 min interval for recovery between subsequent tests.
Although the repeated swimming challenges were performed without a full recovery,
normoxic fish swam just as well on the second swim, and the majority of fish swam
only marginally more poorly on the third swim. In addition, metabolic loading in
these fish, as measured by the rate of oxygen consumption, ventilation rate and
plasma lactate levels during recovery, did not appear to be cumulative with
successive swims. Fish, however, did not recover as well after a similar level of
initial swimming performance under moderately hypoxic conditions (water PO2>100
mmHg; 1 mmHg=0.1333 kPa). Four out of the five fish did not swim again and their
high plasma lactate levels indicated a greater anaerobic effort. In another group
of fish, metabolic loading (elevated control rates of oxygen consumption) was
induced with an overnight sublethal exposure to pentachlorophenol, but these fish
swam as well as normoxic fish on the first swim, and five of the six fish swam
for a third time at a marginally lower critical swimming speed. In contrast to
expectations, pentachlorophenol pretreatment and moderate hypoxia were not
additive in their effects. Instead, the effects resembled those of
pentachlorophenol pretreatment alone. The results are discussed in terms of what
aspects of fatigue might impair the repeat swimming performance of sockeye
salmon.
PMID- 9639593
TI - Cold inhibition of cell volume regulation during the freezing of insect
malpighian tubules.
AB - Cells in freeze-tolerant tissues must survive substantial shrinkage during
exposure to the hyperosmolarity that results as solutes are excluded from
extracellular ice. We investigated the possibility that this hyperosmotic shock
elicits an acute regulatory volume increase (RVI) by monitoring the response of
epithelial cell volume in the Malpighian tubules of the New Zealand alpine weta
(Hemideina maori) during exposure to low temperature/hyperosmolarity (mimicking
freezing conditions) or during an actual freeze/thaw cycle. The cross-sectional
area of cells in isolated Malpighian tubules was measured using differential
interference contrast microscopy. At 20 degrees C, cells held in saline
containing 400 mmol1-1 glucose exhibit an RVI in response to hyperosmotic shock.
Cross-sectional area decreased by 30% immediately after a change from iso-osmotic
(0.7 osmol1-1) to hyper-osmotic saline (2.1 osmol1-1, equal to the osmotic shock
encountered during freezing to -4 degrees C) and then returned to 21% below the
control value 30 min after the exposure. Although substantial cellular function
of Malpighian tubules was retained at low temperature (the rate of fluid
secretion by isolated tubules at 4 degrees C was 72% of that measured at 20
degrees C), no RVI was observed at 0% degrees C; cross-sectional area was 39%
below the control value immediately after the hyperosmotic exposure and 36% below
the control value 30 min after hyperosmotic exposure. Dibutyryl cyclic AMP
potentiated the RVI observed at 20 degrees C, but failed to elicit an RVI at 0
degrees C. A substantial RVI was also absent when the saline contained trehalose
rather than glucose, regardless of whether the tubules were held at 20 degrees C
or 0 degrees C. The cross-sectional area of cells in saline containing glucose
remained at approximately 30% below the control value during an entire 30 min
period of actual freezing to -4 degrees C, suggesting that an acute volume
regulatory response was in fact inhibited during mild freezing. The inhibition of
an acute RVI during mild freezing may serve to avoid the energetic expenditure
associated with volume regulation at a time when the normal defence of cell
volume appears to be unnecessary.
PMID- 9639594
TI - Evidence for membrane-bound carbonic anhydrase in the air bladder of bowfin (Amia
calva), a primitive air-breathing fish.
AB - The purpose of this study was to examine the subcellular distribution and
isoenzyme characteristics of carbonic anhydrase from the gills and respiratory
air bladder of bowfin Amia calva, a primitive air-breathing fish. Separation of
subcellular fractions by differential centrifugation revealed that the vast
majority of carbonic anhydrase from the gills of bowfin originated from the
cytoplasmic fraction. Washing of the gill microsomal pellet also indicated that
the carbonic anhydrase originally associated with this pellet was largely due to
contamination from the cytoplasmic fraction. Experiments with a carbonic
anhydrase inhibitor, sulphanilamide, and the plasma carbonic anhydrase inhibitor
from this species confirmed that the bowfin gill probably contains only one
carbonic anhydrase isoenzyme which had properties resembling those of CA II. In
contrast to the situation in the gills, a relatively large percentage (27%) of
the total air bladder carbonic anhydrase was associated with the microsomal
fraction. Washing of the air bladder microsomal pellet removed little of the
carbonic anhydrase activity, indicating that most of the carbonic anhydrase in
the microsomal fraction was associated with the membranes. Like the mammalian
pulmonary CA IV isoenzyme, microsomal carbonic anhydrase from the bowfin air
bladder was less sensitive to the bowfin plasma carbonic anhydrase inhibitor,
sodium dodecylsulphate (SDS) and sulphanilamide than was cytoplasmic carbonic
anhydrase from the air bladder. Microsomal carbonic anhydrase from the bowfin air
bladder also resembled CA IV in that it appears to be anchored to the membrane
via a phosphatidylinositol-glycan linkage which could be cleaved by
phosphatidylinositol-specific phospholipase C. Taken together, these results
suggest that a membrane-bound carbonic anhydrase isoenzyme resembling mammalian
CA IV in terms of inhibition characteristics and membrane attachment is present
in the air-breathing organ of one of the most primitive air-breathing
vertebrates.
PMID- 9639595
TI - Visual modulation of olfactory learning in honeybees.
AB - We use classical conditioning of the honeybee (Apis mellifera) proboscis
extension reflex with a visual (A) and an olfactory (X) conditioned stimulus in a
blocking paradigm. Typically, learning about one element (X) of a compound (AX)
is decreased (blocked) if the other component (A) has previously been rewarded
alone. Our results show that visual pretraining did not produce blocking in
honeybees: instead, forward pairings of A with a reward increased subsequent
learning about X relative to a backward pairing control. This finding violates
the independence assumption, which holds that elements of inter-modal compound
stimuli change associative strength independently of each other. Furthermore, it
is at odds with common theories of conditioning that predict blocking and assume
that the elements of a compound stimulus rely on one common internal reinforcing
signal. Taking the functional anatomy of the honeybee brain into account, we
suggest that vision and olfaction may not rely on the same internal reinforcing
signal; compound interactions might thus reflect the wiring of the honeybee
nervous system and the biological significance of different sensory modalities
during natural behaviour.
PMID- 9639596
TI - The role of angiotensin in arterial blood pressure regulation in the toad Bufo
marinus.
AB - Little is known about the role of the renin-angiotensin system in anuran
amphibians, although they appear to possess the functional components of such a
system. We investigated the role of angiotensin (ANG) in arterial blood pressure
regulation in the conscious toad Bufo marinus using the angiotensin-converting
enzyme blocker captopril. We found that conversion of endogenous ANG I to ANG II
made a significant contribution to mean arterial pressure in undisturbed animals.
The vascular tone contributed by ANG II was not mediated via &agr ; adrenergic
mechanisms because increases in pressure in response to ANG infusion were
unaffected by the presence of the &agr ; antagonist phentolamine. Angiotensin
induced vasoconstriction was shown to be an important mechanism in arterial blood
pressure regulation in the face of an acute hypotensive perturbation of pressure
brought about by sodium nitroprusside. Blockade of the conversion of ANG I to ANG
II significantly delayed the recovery of mean arterial pressure after sodium
nitroprusside-induced hypotension. This suggests that the renin-angiotensin
system may play an important role in the initial responses to hypotension in
anurans, whether brought about by haemorrhage or dehydration.
PMID- 9639597
TI - Functional citric acid cycle in an arcA mutant of Escherichia coli during growth
with nitrate under anoxic conditions.
AB - The operation of the citric acid cycle of Escherichia coli during nitrate
respiration (anoxic conditions) was studied by measuring end products and enzyme
activities. Excretion of products other than CO2, such as acetate or ethanol, was
taken as an indication for a non-functional cycle. From glycerol, approximately
0.3 mol acetate was produced; the residual portion was completely oxidized,
indicating the presence of a partially active citric acid cycle. In an arcA
mutant devoid of the transcriptional regulator ArcA, glycerol was completely
oxidized with nitrate as an electron acceptor, demonstrating derepression and
function of the complete pathway. Glucose, on the other hand, was excreted mostly
as acetate by the wild-type and by the arcA mutant. During growth on glucose, but
not on glycerol, activities of succinate dehydrogenase and of 2-oxoglutarate
dehydrogenase were missing nearly completely. Thus, the previously described
strong repression of the citric acid cycle during nitrate respiration occurs only
during growth on glucose and is the effect of anaerobic and, more important, of
glucose repression. In Pseudomonas fluorescens (but not Pseudomonas stutzeri), a
similar decrease of citric acid cycle function during anaerobic growth with
nitrate was found, indicating a broad distribution of this regulatory principle.
PMID- 9639598
TI - Aerobic chemolithoautotrophic growth and RubisCO function in Rhodobacter
capsulatus and a spontaneous gain of function mutant of Rhodobacter sphaeroides.
AB - Photosynthetic prokaryotes that assimilate CO2 under anoxic conditions may also
grow chemolithoautotrophically with O2 as the electron acceptor. Among the
nonsulfur purple bacteria, two species (Rhodobacter capsulatus and
Rhodopseudomonas acidophilus), exhibit aerobic chemolithoautotrophic growth with
hydrogen as the electron donor. Although wild-type strains of Rhodobacter
sphaeroides grow poorly, if at all, with hydrogen plus oxygen in the dark, we
report here the isolation of a spontaneous mutant (strain HR-CAC) of Rba.
sphaeroides strain HR that is fully capable of this mode of growth. Rba.
sphaeroides and Rba. capsulatus fix CO2 via the reductive pentose phosphate
pathway and synthesize two forms of ribulose 1, 5-bisphosphate
carboxylase/oxygenase (RubisCO). RubisCO levels in the aerobic
chemolithoautotrophic-positive strain of Rba. sphaeroides were similar to those
in wild-type strains of Rba. sphaeroides and Rba. capsulatus during
photoheterotrophic and photolithoautotrophic growth. Moreover, RubisCO levels of
Rba. sphaeroides strain HR-CAC approximated levels obtained in Rba. capsulatus
when the organisms were grown as aerobic chemolithoautotrophs. Either form I or
form II RubisCO was able to support aerobic chemolithoautotrophic growth of Rba.
capsulatus strain SB 1003 and Rba. sphaeroides strain HR-CAC at a variety of CO2
concentrations, although form II RubisCO began to lose the capacity to support
aerobic CO2 fixation at high O2 to CO2 ratios. The latter property and other
facets of the physiology of this system suggest that Rba. sphaeroides and Rba.
capsulatus strains may be effectively employed for the biological selection of
RubisCO molecules of altered substrate specificity.
PMID- 9639599
TI - Cloning and characterization of a Rhizobium meliloti nonspecific acid
phosphatase.
AB - Nodulated legumes require high levels of phosphorus for optimal symbiotic
performance. However, the basis for this elevated phosphorus requirement is
poorly understood, and very little information regarding bacteroid phosphorus
metabolism is available. To develop an understanding of the relative importance
of organic and inorganic phosphorus sources for bacteroids, we investigated
phosphatase activity in Rhizobium meliloti. An R. meliloti plasmid library clone
that complemented an Escherichia coli phosphatase mutant was isolated, and the
clone was sequenced. The complementing fragment contained a 337-amino-acid open
reading frame that has a potential leader sequence and processing sites
characteristic of periplasmic proteins. The phosphatase activity was located in
the periplasm of R. meliloti and of E. coli containing the cloned gene. The
subunit molecular mass of the cloned phosphatase was 33 kDa, and gel filtration
indicated the active enzyme was a 66-kDa homodimer. Lack of substrate specificity
suggests the cloned gene, napD, encodes a nonspecific acid phosphatase with a pH
optimum of approximately 6.5. An R. meliloti napD transposon-insertion mutant was
constructed, and its symbiotic phenotype was determined to be Fix+ regardless of
the level of phosphorus provided to the host plant.
PMID- 9639600
TI - Carboxin resistance in Paracoccus denitrificans conferred by a mutation in the
membrane-anchor domain of succinate:quinone reductase.
AB - Succinate:quinone reductase is a membrane-bound enzyme of the citric acid cycle
and the respiratory chain. Carboxin is a potent inhibitor of the enzyme of
certain organisms. The bacterium Paracoccus denitrificans was found to be
sensitive to carboxin in vivo, and mutants that grow in the presence of 3'-methyl
carboxin were isolated. Membranes of the mutants showed resistant
succinate:quinone reductase activity. The mutation conferring carboxin resistance
was identified in four mutants. They contained the same missense mutation in the
sdhD gene, which encodes one of two membrane-intrinsic polypeptides of the
succinate:quinone reductase complex. The mutation causes an Asp to Gly
replacement at position 89 in the SdhD polypeptide. P. denitrificans strains that
overproduced wild-type or mutant enzymes were constructed. Enzymic properties of
the purified enzymes were analyzed. The apparent Km for quinone (DPB) and the
sensitivity to thenoyltrifluoroacetone was normal for the carboxin-resistant
enzyme, but the succinate:quinone reductase activity was lower than for the wild
type enzyme. Mutations conferring carboxin resistance indicate the region on the
enzyme where the inhibitor binds. A previously reported His to Leu replacement
close to the [3Fe-4S] cluster in the iron-sulfur protein of Ustilago maydis
succinate:quinone reductase confers resistance to carboxin and
thenoyltrifluoroacetone. The Asp to Gly replacement in the P. denitrificans SdhD
polypeptide, identified in this study to confer resistance to carboxin but not to
thenoyltrifluoroacetone, is in a predicted cytoplasmic loop connecting two
transmembrane segments. It is likely that this loop is located in the
neighborhood of the [3Fe-4S] cluster.
PMID- 9639601
TI - Two malate dehydrogenases in Methanobacterium thermoautotrophicum.
AB - Methanobacterium thermoautotrophicum (strain Marburg) was found to contain two
malate dehydrogenases, which were partially purified and characterized. One was
specific for NAD+ and catalyzed the dehydrogenation of malate at approximately
one-third of the rate of oxalacetate reduction, and the other could equally well
use NAD+ and NADP+ as coenzyme and catalyzed essentially only the reduction of
oxalacetate. Via the N-terminal amino acid sequences, the encoding genes were
identified in the genome of M. thermoautotrophicum (strain DeltaH). Comparison of
the deduced amino acid sequences revealed that the two malate dehydrogenases are
phylogenetically only distantly related. The NAD+-specific malate dehydrogenase
showed high sequence similarity to L-malate dehydrogenase from Methanothermus
fervidus, and the NAD(P)+-using malate dehyrogenase showed high sequence
similarity to L-lactate dehydrogenase from Thermotoga maritima and L-malate
dehydrogenase from Bacillus subtilis. A function of the two malate dehydrogenases
in NADPH:NAD+ transhydrogenation is discussed.
PMID- 9639602
TI - Identification and characterization of IS1302, a novel insertion element from
Wolinella succinogenes belonging to the IS3 family.
AB - A new insertion sequence (IS) designated IS1302 was identified in Wolinella
succinogenes. IS1302 is 1,306 bp in size with 36-bp imperfect terminal inverted
repeats. It contains only one open reading frame (tnpA), which encodes a putative
transposase whose sequence is similar to that of transposases of various IS
elements of the IS3 family. IS1302 was identified in the genome of a W.
succinogenes fumarate reductase deletion mutant in which the frd operon had been
replaced by the kan gene. The insertion of IS1302 occurred when the mutant was
propagated in the presence of a high concentration of kanamycin. Two different
target sites of IS1302 were found immediately upstream of the kan gene, where the
insertion of IS1302 resulted in a duplication of 3 bp of the target DNA. Upon
insertion of IS1302, new possible promoter structures of the kan gene were
created, which might lead to a stimulated transcription of the kan gene and
result in a selective advantage of cells containing IS1302 at one of the two
target sites. Southern blot analysis suggested the presence of at least 13 copies
of IS1302 in the genome of W. succinogenes. This is the first IS element
discovered in W. succinogenes.
PMID- 9639603
TI - Two membrane anchors of Wolinella succinogenes hydrogenase and their function in
fumarate and polysulfide respiration.
AB - Wolinella succinogenes can grow by anaerobic respiration with fumarate or
polysulfide as the terminal electron acceptor, and H2 or formate as the electron
donor. A DeltahydABC mutant lacking the hydrogenase structural genes did not grow
with H2 and either fumarate or polysulfide. In contrast to the wild-type strain,
the mutant grown with fumarate and with formate instead of H2 did not catalyze
the reduction of fumarate, polysulfide, dimethylnaphthoquinone, or benzyl
viologen by H2. Growth and enzymic activities were restored upon integration of a
plasmid carrying hydABC into the genome of the DeltahydABC mutant. The
DeltahydABC mutant was complemented with hydABC operons modified by artificial
stop codons in hydA (StopA) or at the 5'-end of hydC (StopC). The StopC mutant
lacked HydC, and the hydrophobic C-terminus of HydA was missing in the
hydrogenase of the StopA mutant. The two mutants catalyzed benzyl viologen
reduction by H2. The enzyme activity was located in the membrane of the mutants.
A mutant with both modifications (StopAC) contained the activity in the
periplasm. The three mutants did not grow with H2 and either fumarate or
polysulfide, and did not catalyze dimethylnaphthoquinone reduction by H2. We
conclude that the same hydrogenase serves in the anaerobic respiration with
fumarate and with polysulfide. HydC and the C-terminus of HydA appear to be
required for both routes of electron transport and for dimethylnaphthoquinone
reduction by H2. The hydrogenase is anchored in the membrane by HydC and by the C
terminus of HydA. The catalytic subunit HydB is oriented towards the periplasmic
side of the membrane.
PMID- 9639604
TI - Sulfide oxidation in the phototrophic sulfur bacterium Chromatium vinosum.
AB - Sulfide oxidation in the phototrophic purple sulfur bacterium Chromatium vinosum
D (DSMZ 180(T)) was studied by insertional inactivation of the fccAB genes, which
encode flavocytochrome c, a protein that exhibits sulfide dehydrogenase activity
in vitro. Flavocytochrome c is located in the periplasmic space as shown by a
PhoA fusion to the signal peptide of the hemoprotein subunit. The genotype of the
flavocytochrome-c-deficient Chr. vinosum strain FD1 was verified by Southern
hybridization and PCR, and the absence of flavocytochrome c in the mutant was
proven at the protein level. The oxidation of thiosulfate and intracellular
sulfur by the flavocytochrome-c-deficient mutant was comparable to that of the
wild-type. Disruption of the fccAB genes did not have any significant effect on
the sulfide-oxidizing ability of the cells, showing that flavocytochrome c is not
essential for oxidation of sulfide to intracellular sulfur and indicating the
presence of a distinct sulfide-oxidizing system. In accordance with these
results, Chr. vinosum extracts catalyzed electron transfer from sulfide to
externally added duroquinone, indicating the presence of the enzyme
sulfide:quinone oxidoreductase (EC 1.8.5.-). Further investigations showed that
the sulfide:quinone oxidoreductase activity was sensitive to heat and to quinone
analogue inhibitors. The enzyme is strictly membrane-bound and is constitutively
expressed. The presence of sulfide:quinone oxidoreductase points to a connection
of sulfide oxidation to the membrane electron transport system at the level of
the quinone pool in Chr. vinosum.
PMID- 9639605
TI - Liver transplantation in children.
PMID- 9639606
TI - Pediatric liver transplantation: from the full-size liver graft to reduced,
split, and living related liver transplantation.
AB - Between 1984 and 1996, the authors performed 499 liver transplants in 416
children less than 15 years old. The overall patient survival at 10 years was
76.5%. It was 71.3% for the 209 children grafted in 1984-1990; 78.5% for biliary
atresia (n = 286), 87.3% for metabolic diseases (n = 59), and 72.7% for acute
liver failure (n = 22). The 5-year survival was 73.6% for the 209 children
grafted in 1984-1990 and 85% for the 206 grafted in 1991-1996. Scarcity of size
matched donors led to the development of innovative techniques: 174 children who
electively received a reduced liver as a first graft in our center had a 5-year
survival of 76% while 168 who received a full-size graft had a survival of 85%
(NS). Results of the European Split Liver Registry showed 6-month graft survival
similar to results obtained with full-size grafts collected by the European Liver
Transplant Registry. Extensive use of these techniques allowed the mortality
while waiting to be reduced from 16.5% in 1984-1990 to 10% in 1991-1992. It rose
again to 17% in 1993, leading the authors to develop a program of living related
liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between
July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In
elective cases, a detailed analysis was made of the 45 children listed for LRLT
between July 1993 and March 1997 and the 79 registered on the cadaveric waiting
list during the same period. Mortality while waiting was 2% and 14.5% for the
LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and
16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant
survival was 88% and 82% for children who received a LRLT or a cadaveric graft,
respectively. Overall survival from the date of registration was 86% and 70% (P <
0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival
in children less than 1 year of age at transplantation was 88.8% and 80. 3% with
a LRLT or cadaveric graft, respectively; patient survival after 3 months post
transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and
93.7% in children hospitalized for complications of their disease, and 89.5% and
77.7% for children hospitalized in an intensive care unit at the time of
transplantation for children who received a LRLT or cadaveric graft,
respectively. It is concluded that LRLT seems to be justified for
multidisciplinary teams having a large experience with reduced and split liver
grafting.
PMID- 9639607
TI - Development of a pediatric liver transplantation program in Argentina.
AB - This article describes the preliminary experimental steps and clinical
implementation of a purely pediatric liver transplantation (LT) program in a
large public children's hospital in Buenos Aires, Argentina, a city with well
over 10 million inhabitants and a referral population of over 30 million. Between
1993 and 1997, 84 LTs were performed in 81 patients, of which one-fourth weighed
below 10 kg. The main indications were biliary atresia (n = 25, 30%) and
fulminant liver failure (n = 23, 27%), followed by autoimmune cirrhosis (n = 14,
16%) and other liver diseases. Shortage of organs due to local conditions led to
the use of liver-reduction techniques in 48 cases (57%), split liver in 2, and
living-related donor (LRD) in 2. Retransplantation was necessary in 3 instances.
Seventy-eight percent of the recipients survived for more than 1 year and 71%
were alive after 4 years. The authors comment on the need for adaptation to local
conditioning factors when developing a pediatric LT program in any country in
which demographics and economic, medical, and sociological environments have a
decisive influence on organ procurement, the actual performance of the operation,
and the lifelong postoperative medication. In Buenos Aires, where the hospital
setting is well-developed, the indications are in part determined by the high
incidence of hepatitis A. Organ shortages in our area led to liberal use of liver
reduction, split-liver, and LRD techniques. The overall results of the first
years of such a program were largely satisfactory.
PMID- 9639608
TI - Changes in growth, growth hormone, and insulin-like growth factor-I (IGF-I) after
orthotopic liver transplantation.
AB - Growth failure is an important consequence of chronic liver disease in childhood.
Insulin-like growth factor-I (IGF-I), which is synthesized and released by the
liver, plays an important role as a growth regulator in humans. We examined the
growth hormone (GH)/IGF-I axis before and after orthotopic liver transplantation
(LT) in 14 children aged between 2 and 11 years (mean 5.6 +/- 1.1 years). Pre
transplantation serum GH levels (7.5 +/- 1.2 ng/ml) were significantly higher (P
< 0.001) compared with controls (5 +/- 0.5 ng/ml). However, post-transplantation
levels (1.8 +/- 0.8 ng/ml) did not differ from those in the control group. Serum
IGF-I levels showed a statistically significant increase after LT (20.1 +/- 9.4
vs 190 +/- 66.2 ng/ml; P < 0.001) and became indistinguishable from the levels in
the control group (180 +/- 96 ng/ml). In comparison with pre-transplantation data
(z - 2.70), there was an increase in height 4 years postoperatively (z - 1.68).
Catch-up growth was highly significant, in particular during the 1st year after
LT (z -1. 58 +/- 1.63 vs 2.59 +/- 5.29; P < 0.01). We conclude that a GH
resistance state found in patients with severe chronic liver disease reverted
following LT. Given that IGF-1 depends upon liver function, this could be one of
the main factors in the significant catch-up growth in pediatric LT recipients.
PMID- 9639609
TI - Long-term follow-up of patients with biliary atresia successfully treated with
hepatic portoenterostomy. The importance of sequential treatment.
AB - The outcome of 18 biliary atresia (BA) patients (5 male, 13 female; age range
10.7-22.5 years; mean 15.4+/-0.7 years) treated with hepatic portoenterostomy
(HPE) and jaundice-free for more than 10 years without liver transplantation (LT)
is analyzed retrospectively. Eight of these patients subsequently required LT
(age at LT 12. 8+/-0.5 years, range 10.5-15.2 years); 3 children (aged 11.6, 13.2
and 14.1 years, respectively) had episodes of gastrointestinal variceal bleeding
associated with other signs of severe disease and are now candidates for LT; and
among the 7 asymptomatic patients (age range 11.2-22.5 years; mean 15.9+/-2.1
years), 5 had sonographic and biochemical signs of moderate portal hypertension
(PH). In order to analyze whether the age at transplantation influences the
survival of children transplanted for BA, we also reviewed the outcome of 71 BA
patients transplanted at our hospital between 1986 and 1996. All the children
older than 10 years at the time of LT were alive; only patients younger than 10
years died following LT (n = 15). We conclude that the natural outcome of
extrahepatic BA is toward PH, fibrosis, and cirrhosis, even in those cases
successfully treated with HPE. In our experience, the results of sequential
treatment with HPE and LT were excellent.
PMID- 9639610
TI - Evidence-based operations in paediatric surgery.
AB - It has been assumed that only 10% of medical interventions are supported by solid
scientific evidence. The aim of this study was to determine the type of research
evidence supporting operations in a tertiary referral paediatric surgical unit.
All patients admitted over a 4-week period to two surgical firms were enrolled in
the study. All major operations carried out on each patient since birth were
evaluated. Patients for whom a diagnosis was not reached were excluded. A
bibliographic database (MEDLINE) was used to search for the articles published
between January 1986 and December 1995 on the analysed operations. The type of
evidence supporting the operations was classified as follows: I=evidence from
randomised controlled trials (RCTs); II=self-evident intervention (obvious
effectiveness not requiring RCTs); III=evidence from prospective and/or
comparative studies; IV=evidence from follow-up studies and/or retrospective case
series; and V=intervention without substantial evidence for or against results of
randomised trials. Seventy operations (32 individual types) were performed on 49
patients (1-5 operations/patient); 18 (26%) were supported by RCTs (type of
evidence I). Two patients (3%) received a self-evident intervention (type II); 48
operations (68%) were based on non-randomised prospective or retrospective
studies (type III=13%; type IV=55%). Two patients (3%) received an operation not
supported by or against convincing scientific evidence (type V). A significant
proportion of operations in paediatric surgery is supported by RCTs. However, the
vast majority of these trials were conducted on adult patients. Sixty-eight per
cent of the operations were based on prospective follow-up studies or
retrospective case series, which may not represent solid scientific evidence.
More RCTs are needed in paediatric surgery.
PMID- 9639611
TI - Oesophageal replacement in the management of corrosive strictures: when is
surgery indicated?
AB - The accidental ingestion of corrosive agents is a major cause of oesophageal
strictures in children. The mainstay of treatment is repeated dilatations.
Despite this, a significant number of patients eventually require oesophageal
bypass. We reviewed the records of all cases managed with this condition at the
University of Cape Town teaching hospitals between 1976 and 1994. Dilatation
therapy alone was successful in 14 out of 39 patients (41%). Morbidity of failed
dilatation therapy included repeated hospital admissions over an average 11.5
months and 17 dilatations each. Oesophageal perforations occurred in 7 cases
(18%). Early factors predictive of failure of conservative treatment were: delay
in presentation of more than 1 month; severe pharyngo-oesophageal burns requiring
a tracheostomy; oesophageal perforation; and a stricture longer than 5 cm on
radiological assessment. The size of dilators accepted during early bougienage
also correlated with eventual outcome. These criteria may be useful in predicting
which patients will not respond to repeated dilatations. Early surgical
intervention in such cases will prevent fruitless dilatations and related
complications.
PMID- 9639612
TI - Longitudinal follow-up of pulmonary function after lobectomy in childhood -
factors affecting lung growth.
AB - We examined the changes in pulmonary function values in 27 patients who underwent
a lobectomy due to cystic lung disease and compared the results regarding such
factors as disease type, age at operation, and preoperative infections. Percent
vital capacity (%VC) decreased immediately after lobectomy, but recovered to
normal values within 2 postoperative years and remained within or above the
normal range. The ratio of residual volume to total lung capacity (RV/TLC) rose
temporally with the increase in %VC, but then remained normal after 2
postoperative years. There was no difference in %VC and RV/TLC between diseases,
while bronchial atresia showed a significantly lower correlation with percent of
forced expiratory volume at 1 s. The older group operated upon at over 4 years of
age and the group that had infections before operation showed relatively low %VC
and high RV/TLC. Some patients demonstrated extremely low %VC along with funnel
chest deformities. Our study suggests that overinflation of the remaining lung
compensates VC in the early period after lobectomy while subsequently alveolar
multiplication occurs. Factors affecting compensatory lung growth were considered
to be operation later than 4 years of age, preoperative infection, and a thoracic
deformity.
PMID- 9639613
TI - Gastric necrosis in newborns: a report of 11 cases.
AB - Eleven neonates ranging in gestational age from 34 to 40 weeks presented with
gastric necrosis. The 4 full-term neonates showed sudden-onset hemorrage and
"coffee-ground" vomiting; in the 7 premature babies the initial clinical finding
was abdominal distention. The criteria for diagnosis were: perinatal distress in
prematures and transient neonatal respiratory distress in full-term babies.
Radiographic evidence of gastric distention was typical and preceded clinical
signs of hematemesis and gastric perforation. Surgery was performed in 8
patients; 3 received medical treatment. At surgery 1 total and 3 subtotal
gastrectomies and 4 segmental gastric resections were performed. Three of these
patients died post-operatively as a consequence of multiorgan failure; a second
look was necessary in one patient 1 week after surgery because of prepyloric
perforation due to ulcers. Biopsy specimens taken from the site of perforation
demonstrated extensive necrosis; ulceration was disseminated in the surrounding
gastric mucosa; no signs of phlogosis were detected. The diagnosis, treatment,
and physiopathologic considerations are reviewed.
PMID- 9639614
TI - The influence of laparoscopic surgery on perioperative heat loss in infants.
AB - Perioperative heat loss is a potentially serious complication of surgery in
infants. The influence of laparoscopic surgery on perioperative hypothermia has
not previously been documented. We reviewed heat loss in 26 infants undergoing
laparoscopic pyloromyotomies compared with 42 control patients having the
standard open procedure over the same time period. The mean fall in temperature
in the laparoscopic group was -0.69 degreesC compared with -0.47 degreesC in the
open group. This difference was not significant, with a P value of 0.077. This
may reflect the small sample size and the relatively short duration of this
procedure with few instrument changes. There was a trend for increased heat loss
in the laparoscopic group, which might have implications for longer and more
complex laparoscopic procedures in infants.
PMID- 9639615
TI - The use of laparoscopy in the diagnosis and treatment of abdominal complications
of ventriculo-peritoneal shunts in children.
AB - Ventriculo-peritoneal shunts (VPS) are the most frequent operative procedures
used to treat hydrocephalic children. Abdominal complications of VPS are now a
rare event; however, their frequency varies from 5% to 47% according to reports.
Anything that causes an obstruction or impediment of the VP derivation system
will lead to intracranial hypertension, which requires immediate surgery. From
1985 to 1995 at the Division of Pediatric Surgery of the Federico II University
of Naples, ten laparoscopies were performed in ten children with VPS
complications. Cerebrospinal fluid pseudocysts were found in four infants. There
was one case of abdominal wall perforation by the tip of the catheter at the
umbilical level, two bowel obstructions, and one catheter was lost in the
abdominal cavity. Finally, two children had malfunctioning of the peritoneal limb
of the catheter. The laparoscopic technique was curative in all ten cases, thus
avoiding a conventional laparotomy and the consequent risk of adhesions, which
could cause further complications.
PMID- 9639616
TI - Multidisciplinary evaluation of the distended abdomen in critically ill infants
and children: the role of bedside sonography.
AB - Abdominal distention and metabolic acidosis are common in critically ill infants
and children, and can be manifestations of an intra-abdominal catastrophe. This
series demonstrates the value of bedside sonography (US) in this difficult
assessment. Eight infants and children presented with the above situation. Seven
were immediately post-cardiopulmonary resuscitation and none had antecedent
histories of abdominal pain or bilious vomiting. Abdominal radiographs could not
rule out intra-abdominal pathology such as ischemic bowel. Review of all
laboratory and radiological data showed US to be a discerning modality for acute
bowel pathology. A characteristic pattern of echogenic ascites, thickened bowel
wall, dilated, fluid-filled bowel lumen, and lack of peristalsis was seen in
those children with gangrenous bowel. Sonographic examination accurately
predicted the status of the bowel in all patients. Four patients survived: two
had segmental ileal necrosis, one had localized gangrene of the jejunum (twice),
and one had necrotic bowel from a closed-loop obstruction. The four who died had
malrotation with volvulus (two), superior mesenteric venous thrombosis, and one
was immunocompromised with pulmonary aspiration. We conclude that bedside US can
be extremely valuable as an adjunct in assessing the abdomen and diagnosing
gangrenous bowel in critically ill infants and children.
PMID- 9639617
TI - Reliability of color Doppler and power Doppler sonography in the evaluation of
intussuscepted bowel viability.
AB - In two similar cases of irreducible intussusception with wall necrosis and
perforation, symptoms had begun 24 h before admission and the plain radiographs
showed signs of small-bowel obstruction. The sonographic (US) appearances,
however, were different: color Doppler (CD) US showed vascular flow in the
intussuscepted bowel in one case and no flow in the other. After radio-clinical
assessment, both children underwent surgery and an intestinal resection had to be
performed, manual reduction being impossible. The reliability of the US findings
and the prognostic value of CD and power Doppler US in determining the viability
of the intussuscepted bowel are discussed with a review of the literature.
PMID- 9639618
TI - Intestinal volvulus and right-sided blunt trauma: consequence or coincidence?
AB - Two boys developed bile-stained vomiting shortly after being involved in
significant right-sided blunt trauma and sustaining fractured right femurs. Both
had intestinal volvulus and both had a history of bile-stained vomiting in
infancy, which had been investigated and interpreted as normal.
PMID- 9639619
TI - Meconium ileus secondary to cystic fibrosis. The East London experience.
AB - Meconium ileus (MI) affects 15% of neonates with cystic fibrosis (CF). The
authors reviewed the management and outcome of 51 neonates presenting to a single
institution between 1976 and 1995 with MI secondary to CF. Clinical presentation
included abdominal distension (96%), bilious vomiting (49%), and delayed passage
of meconium (36%). A family history of CF was present in 4 cases (8%). Twenty
three neonates presented with MI and evidence of volvulus, atresia, or
perforation (complicated MI). Of these, 16 underwent stoma formation, 1
appendicectomy, and 6 resection with primary anastomosis. Twenty-eight neonates
presented with uncomplicated MI. Of these, 11 were managed non-operatively by
Gastrografin enema (10) or enteral N-acetylcysteine (1). The remainder required
stoma formation (15) or bowel resection with primary anastomosis (2). Early
postoperative complications occurred in 2 neonates (4%). In this hospital the 1
year survival for this condition has increased from 49% (1953-1970) to 98% (1976
1995) irrespective of the surgical procedure performed or the presence of
volvulus, atresia, or perforation. In our experience, bowel resection with
primary anastomosis is as safe as stoma formation and is associated with a
reduced length of initial hospital stay.
PMID- 9639620
TI - The Malone antegrade colonic enema procedure: outcome and lessons of 6 years'
experience.
AB - The successful management of faecal incontinence can dramatically improve the
quality of life of affected children. The introduction of the non-refluxing,
catheterisable appendico-caecostomy provides the opportunity to treat previously
resistant patients. Over a 6-year period, 29 children had a Malone antegrade
continent stoma for enema administration (MACE). Incontinence was related to
spina bifida in 12 children, ano-rectal anomaly in 12, Hirschprung's disease in
2, followed excision of a pelvic tumour in 2, and was secondary to intractable
chronic constipation in 1. The conduit was fashioned from the appendix (20), a
caecal tube (8), or a gastric tube (1). Surgical complications were stomal
stenosis (11), wound infection (1), anastomotic leak (1), MACE stoma prolapse
(1), and a pressure sore (1). Colonic irrigation was achieved with washouts of
saline (24), saline plus phosphate (4), and saline plus Picolax (1). Twenty-three
patients have complete control of bowel function, but 4 still soil. Two remain
incontinent, 1 of whom is still being instructed. One child subsequently had a
colostomy, but still uses the MACE stoma. Successful bowel management requires
motivation, dedication, commitment, and the input of a clinical nurse specialist.
The MACE is a relatively straightforward operative procedure that provides an
effective washout technique that is acceptable to both parents and children.
PMID- 9639621
TI - Duplication of the rectum: report of four cases and review of the literature.
AB - Rectal duplications are rare anomalies. Recently, we observed four cases of
rectal duplication, each presenting with different clinical features including
chronic constipation, a prolapsing rectal "polyp, " a "growth" from the vulva,
and acute retention of urine. The variety of clinical presentations may lead to
delay in diagnosis and multiple operations.
PMID- 9639622
TI - Parenting children with anorectal malformations: implications and experiences.
AB - Parents play a crucial role in the life of a child suffering from an anorectal
malformation (ARM), since their guidance contributes to the degree to which the
child learns to cope with his or her disability. We investigated whether they
experience stress in parenting such a child and also attempted to identify
somatic or behavioral characteristics in the child that influence the stress of
parenting. The parents of 109 children (69 males, 40 females; median age 5.9
years, range 1-18 years) with an ARM (58 low, 10 intermediate, 41 high) were
studied. The Nijmegen Questionnaire on Child-rearing Situations (NQCS) was used
to investigate the existing parenting situation. Behavioral characteristics of
the children were studied by means of the Child Behaviour Checklist (CBCL) and
the Teacher Report Form (TRF). In a semi-structured interview, we investigated
how parents experienced the implications of the disability in everyday life with
their child. Our study showed that as far as the perception of parenting stress
is concerned, parents of children with an ARM do not differ from those with
healthy primary-school children. Within the group of parents with ARM-afflicted
children, the parents of older, incontinent children experienced relatively more
stress, especially when the child concerned was male. With regard to the
children's behavior, the parents and teachers under investigation did not report
a higher than normal incidence of deviant behavior. However, when individual
parents observed difficult behavior in their child, they found it harder to deal
with than the incontinence for feces. Regarding the implications of the disorder
for their everyday lives, parents were concerned and indicated a need for
specific counselling. We conclude that having a child with a somatic affliction,
in this case an ARM, does not automatically imply that the parents experience
child-rearing problems. However, certain groups of parents are more at risk,
i.e., parents with older, incontinent sons and parents with children exhibiting
behavioral problems. In addition, our study shows that parents do have
difficulties in coping with the implications of the disorder and express a need
for support. We feel that patient care can be improved if aid is tailored to
these specific problems.
PMID- 9639623
TI - Torsion of the adnexa in children: the value of laparoscopy.
AB - Experience with adnexal torsion in neonates and children is often disappointing.
Delay between the first symptoms and operation is important, and adnexal loss the
rule. The authors reviewed their experience and the literature to assess the
appropriate diagnostic and therapeutic approach. Diagnostic procedures (standard
ultrasonography [US], color Doppler US, computed tomography, magnetic resonance
imaging, endorectal US, and diagnostic laparoscopy) are discussed; for neonates
and premenarcheal girls a specific surgical approach is proposed. Twenty-seven
adnexal torsions treated between 1985 and 1995 in the same institution were
retrospectively reviewed. Neonatal (7) and premenarcheal cases (20) were
separated. The neonatal cases (7) were all operated upon: 4 adnexectomies, 2
oophorectomies, and 1 detorsion with cystectomy were performed. In the
premenarcheal group (20) 8 adnexectomies, 6 oophorectomies, 5 detorsions with
cystectomy, and 1 salpingectomy were performed. There were only 6 salvaged adnexa
in this series. In the neonatal group, US seemed accurate in predicting
complicated cases. Prenatal puncture of large (>40 mm) ovarian cysts is possible.
The authors advocate a laparoscopic approach in the first days of life of all
uncomplicated cysts independent of size in order to increase the percentage
salvaged. In ultrasonic complicated cases a delayed operation is proposed in the
premenarcheal group, endorectal US will probably become the diagnostic method of
choice for complicated ovaries; other methods were disappointing. In order to
increase adnexal salvage, the authors recommend a laparoscopic approach in the
emergency situation if a clinical examination is positive as well as better
medical (pediatricians, gynecologists) and general (girls, parents) information.
They suggest controlateral oophoropexy in cases of torsion of a normal adnexum.
PMID- 9639624
TI - Effect of cyclosporine on fertility in male rats.
AB - The effect of cyclosporine (CsA) on fertility has assumed greater importance with
the increasing numbers of pediatric transplantations being performed all over the
world. Conflicting reports on the effects of CsA on sex hormones are available.
This experimental animal study was designed to examine the effect of CsA on
testicular weight, sperm counts, seminiferous tubular diameter (STD), testicular
morphology, DNA flowcytometry, sex hormone levels, and fertility in male rats.
Those rats who received CsA (20 mg/kg per day) showed significant reductions in
testicular weight (P < 0.05), sperm count (P < 0.01), Johnsen score (P < 0.05),
STD (P < 0.01), serum testosterone levels (P < 0.05), haploid cell population (P
< 0. 001) in the testis, and fertility (P < 0.001) compared to those receiving
CsA 10 mg/kg per day and control rats. These findings will have an important
bearing for children receiving cyclosporine for long periods to guide the
physician in optimally adjusting long-term treatment.
PMID- 9639625
TI - Fertility and unilateral undescended testis in the rat model II.
AB - Continuing experimental work on the effect of experimentally created unilateral
undescended testis (UL-UDT) in neonatal rats, this study examined the fertility
and correlated it to contralateral (CL) testicular morphology, seminiferous
tubular diameter (STD), DNA flowcytometry, and the presence of serum anti-sperm
antibodies (ASA) at 120-135 days of age. In our previous reported work, the
fertility of rats with UL-UDT at 65-80 days of age was the same as that of
controls. In the present study the rats with UL-UDT had significantly reduced
fertility (P < 0.01) compared to controls, even though the Johnsen scores and
mean STD of the CL testicular tissue were comparable. DNA flowcytometry
demonstrated a significant decrease (P < 0.001) in haploid cell population in the
CL testicular tissue of rats with UL-UDT. Furthermore, the rats with UL-UDT who
either received an immunosuppressive or in whom the UDT was excised early showed
almost normal fertility and DNA histograms like those of controls. Significantly
high titres of serum ASA were detected only in the group with UL-UDT when tested
at 135 days of age. From these results, in combination with earlier results on
similar work, it may be inferred that UL-UDT causes immunologically-mediated,
progressive damage to the CL descended testis, leading to a decrease in fertility
in rats.
PMID- 9639626
TI - Upper-tract changes after treatment of posterior urethral valves.
AB - This paper discusses the long-term sequelae in the upper urinary tract with
respect to hydroureteronephrosis (HUN), vesicoureteral reflux (VUR), renal
parenchymal disease, and their correlation with renal function in 84 boys with
posterior urethral valves followed for 1 to 21 years. Thirty-one boys (39.3%)
were adolescents or older at the time of review. The incidence of high-grade VUR
(grade III or more) was 47.6% at presentation, and resolution following
decompression of the lower urinary tract occurred in 38.7% of refluxing units.
VUR was associated with a high incidence of chronic renal failure (CRF) (30%) on
long-term follow up; however, 16% of non-refluxing patients also progressed to
CRF. The incidences of renal parenchymal disease and persistent upper-tract
dilatation in the non-refluxing group were 25% and 50% of renal units
respectively. Gross HUN persisted in 12.3% of patients despite decompression and
reconstructive surgery, with vesicoureteral junction (VUJ) obstruction being
documented in 1 patient only. Moderate and mild upper-tract dilatation persisted
in 31.6% and 43.9% of patients, respectively. Persistent gross HUN was associated
with a very high incidence of CRF (92.3%), while 88.4% of those with persistent
mild/moderate dilatation maintained normal renal function over a follow-up period
ranging from 1 to 21 years. This study emphasizes the need for systematic
evaluation to exclude VUJ obstruction and abnormal urodynamics as a cause of
persistent HUN so that effective therapy can be instituted early to relieve back
pressure and to provide a low-pressure reservoir with effective emptying. In the
absence of either of these causes, persistent ureterectasis after treatment is
presumably due to secondary peristaltic failure as a consequence of ureteral
fibrosis, ureteral tortuosity, or developmental dysplasia.
PMID- 9639627
TI - The evolution of biofilms in venous access devices implanted in children with
Wilms' tumour.
AB - Biofilms form on all implanted foreign materials. In venous access ports (VAPs),
the biofilm with entrapped organisms may be the source of recurring bacteraemia.
At present, little is known of the development of biofilms in VAPs. In this study
light, scanning, and transmission electron microscopy were used to investigate
the evolution of biofilms in VAPs implanted in 15 African children with Wilms'
tumour. The VAPs were removed either emergently because of infection (n = 6) or
blockage (n = 3), or electively at the end of chemotherapy (n = 6). Intact
biofilms were obtained from lengths of the catheter attached to ports that had
been in place for 11 days to 3 years. Each was prepared for light and electron
microscopy. In infected ports, shortly after implantation biofilms were thin and
comprised of apparently healthy erythrocytes (RBCs) and occasional platelets,
leucocytes (WBCs), and bacteria enmeshed in a network of fibrin. Three weeks
after implantation, RBCs had autolysed and large numbers of WBCs and bacterial
colonies were present within and on the luminal surface. In 1 instance, the lumen
of a VAP had been occluded by a "plug" of WBCs. In non-infected patients, the
biofilms in long-standing VAPs were of varying thickness and primarily composed
of an amorphous granular material. In most cases, healthy and necrotic bacteria
were present both within the core and on the surface of the biofilms. The results
suggest that while bacteria, per se, are an important factor, the presence and
degradation of blood components may be an equally important factor in the
development of biofilms in VAP catheters.
PMID- 9639628
TI - An outbreak of post-surgical wound infections due to Mycobacterium abscessus.
AB - An outbreak of post-operative wound infections due to Mycobacterium abscessus is
described. During a 5-month period 45 post-surgical patients developed wound
infection, manifested by wound breakdown, cellulitis, and discharge and
progressing slowly to suppuration and sinus formation. The majority (43/45) had
undergone out-patient operations, and 40 had had surgery in the inguinal region.
The source of infection was identified as contaminated tap water. A study
revealed serious deficiencies in the disinfection and sterilisation techniques
employed in the operating theatre (OT), including major defects in the
autoclaving machine. The outbreak was controlled after several specific measures
were instituted. The patients responded well to treatment with conventional first
line anti-tuberculous drugs administered for 3-8 months. The report highlights
the necessity of strict monitoring of disinfection and sterilisation techniques
in surgical units and OTs.
PMID- 9639629
TI - To tube or not to tube: do infants and children need post-laparotomy gastric
decompression?
AB - The purpose of this study was to evaluate the role of nasogastric (NG)
decompression after laparotomy in pediatric surgical practice: 94 children who
underwent abdominal surgery by a single surgeon were consecutively prospectively
managed without postoperative NG tubes. Patients with either bowel obstruction or
intra-abdominal infection were excluded from the study. These children were
compared with 94 retrospective, matched controls who were routinely managed with
postoperative NG decompression by the same surgeon. Data were analyzed with
regard to patient, operative, and outcome variables. There was no difference in
gender, age (3.8 +/- 0.5 vs 3.5 +/- 0.4 years, P > 0.7), or postoperative
complications (P > 0.8) between the two groups. However, there was a higher
incidence of postoperative vomiting (22% vs 11%, P > 0.05) in the children who
did not have postoperative NG decompression. Nevertheless, a significant decrease
in time to first feed, first stool, and discharge was noted in the group of
patients managed without NG tubes (P < 0.05). NG decompression thus need not be
routinely used in the pediatric patient undergoing abdominal surgery, as there is
no difference in postoperative complications and the hospital stay is shortened.
PMID- 9639630
TI - Esophageal hiatal hernia after omphalocele repair.
AB - Esophageal hiatal hernias (EHH) are probably caused by congenital, traumatic, or
iatrogenic factors, although the etiology remains unknown. EHHs may develop after
abdominal wall closure for omphalocele or gastroschisis due to the increased
intra-abdominal pressure, however, there have been few reports in the literature.
We present a case of EHH developing after abdominal wall closure.
PMID- 9639631
TI - Congenital microgastria: a case report and review of literature.
AB - Congenital microgastria is an uncommon result of impairment of normal foregut
development. To date, only 39 cases have been described in the literature. We
report a boy born with microgastria and bilateral hypoplastic kidneys who had
feeding problems, resulting in failure to thrive and growth retardation. After a
short period of conservative management, he was operated upon at the age of 11
months. A Hunt-Lawrence pouch was created, leading to toleration of increasing
amounts of oral feeding. Although his feeding problems have decreased, his height
and weight are below normal (<10th percentile). The embryology, clinical
presentation, diagnostic procedures, associated anomalies, and management are
discussed.
PMID- 9639632
TI - Rapid enlargement of a choledochal cyst: antenatal diagnosis and delayed primary
excision.
AB - A case of choledochal cyst (CC) antenatally diagnosed at 29 weeks' gestation is
reported. Rapid enlargement of the cyst soon after delivery resulted in complete
gastric outlet obstruction (GOO). The lesion was treated by external drainage as
a temporary maneuver, with delayed cyst excision and hepaticoduodenostomy at the
hepatic hilum performed at 81 days of age. Surgical treatment of CC in early
infancy has been reported to be safe and effective. However, delayed primary
excision would be an alternative procedure, especially in rare cases showing
rapid enlargement resulting in GOO, since this choice has the potential advantage
of allowing weight gain and improved nutritional status without risking interim
complications due to the drainage procedure.
PMID- 9639633
TI - Colonic atresia secondary to a choledochal cyst.
AB - Colonic atresia and choledochal cyst are both uncommon congenital abnormalities.
We report a case in which the two conditions coexisted and propose an
aetiological link.
PMID- 9639634
TI - Spiral computed tomography for bilioenteric anastomotic stricture.
AB - Spiral computed tomography scanning after intravenous cholangiography (IVC-SCT)
was used to assess the anatomy of the biliary tree and anastomosis in a 7-year
old girl with recurrent cholangitis 5 years after surgical excision of a
choledochal cyst. The technique clearly visualized the stenosis of the
hepaticojejunostomy and hepatic duct and the dilated intrahepatic ducts. IVC-SCT
provides a precise, prompt, and accurate image with minimal invasiveness and is
especially suitable for the preoperative evaluation of pediatric patients.
PMID- 9639635
TI - Splenic torsion in the presence of renal agenesis.
AB - A 14-year-old male with left renal agenesis presented with a history of
intermittent abdominal pain for over 1 year. At laparotomy, the cause was found
to be splenic torsion. The case is presented with a literature review. A theory
of the cause is also presented based on the regional anatomy and embryology.
PMID- 9639636
TI - Cystic degeneration of heterotopic pancreas.
AB - The case of a large cyst arising from heterotopically-situated pancreatic tissue
in an 11-month-old girl is reported. This is the first published report of
childhood pancreatic cyst that developed in heterotopic pancreatic tissue. There
is strong evidence to suggest that the cyst became symptomatic as a result of
secondary infection, an additional unreported phenomenon. This case serves to
underscore the fact that pancreatic cysts should be considered in the
differential diagnosis of intestinal duplication cysts of childhood.
PMID- 9639638
TI - Large, septated ileal duplication cyst in a 4-year old, simulating the urinary
bladder.
AB - A 4-year-old boy presented with acute abdominal pain and a 1-year history of
intermittent umbilical complaints. Ultrasonographic examination demonstrated a
large cyst in the lower abdomen divided by a thin membrane. With micturition,
impaired bladder function was expected. Initial suprapubic drainage produced
1,000 ml dark-brown liquid. Laparotomy revealed an ileal duplication cyst.
Preoperative computed tomography and laparoscopy with the cyst drained did not
further clarify the diagnosis.
PMID- 9639637
TI - Intraluminal hamartoma of the ileum in a child: a rare cause of intestinal
occlusion.
AB - A case of small-intestinal obstruction in a 12-year-old boy caused by an
intraluminal hamartoma of the ileum is reported. The rarity of the lesion, its
location, symptomatology, histology, and diagnosis are discussed.
PMID- 9639639
TI - An unusual domestic accident: a penetrating abdominal wound with intestinal
evisceration in a child.
AB - We report a penetrating abdominal injury due to a piece of glass, a very unusual
domestic accident, in a 2-year-old boy who was admitted to the emergency
department with an evisceration through the umbilicus. His mother reported that
she was asleep when the boy came to her room, and did not know how it had
happened. We primarily suspected child abuse, but the presence of a piece of
glass in the boy's heel led us to think of a domestic accident. He had poured
himself a glass of water, and then fell on the glass. We could not find a similar
case in the literature on domestic accidents.
PMID- 9639640
TI - Currarino's triad: an unusual cause of constipation in children.
AB - A 6-year-old girl presented with intractable constipation. On investigation, she
was found to have an association of anorectal stenosis, anterior sacral defect,
and anterior meningocoele (Currarino's triad). The meningocoele was excised and a
Duhamel pull-through procedure performed after resection of a massively distended
rectosigmoid. Post-operatively, she started having spontaneous bowel action.
Early diagnosis and management is recommended to avoid the high mortality and
morbidity associated with this condition.
PMID- 9639641
TI - Neonatal scrotal faecal fistula.
AB - Incarceration of a congenital inguinal hernia, if untreated promptly, can result
in dreaded complications like faecal fistula. We report one neonate who presented
with a scrotal faecal fistula due to late presentation.
PMID- 9639642
TI - Cystic lymphangioma of the scrotum.
AB - A 7-year-old boy who presented with a painful left hemiscrotal mass was diagnosed
with acquired lymphangioma of the scrotum. Chronic friction from a cast for
Perthes' disease might have been the cause of sudden enlargement of a congenital
lymphangioma of the scrotum. Magnetic resonance imaging (MRI) was useful for
preoperative diagnosis and determining the extent of the scrotal lesions. Total
excision of the mass leaving the overlying skin was successfully performed. The
clinical significance of MRI for preoperative diagnosis and planning surgical
resection of this lesion is discussed.
PMID- 9639643
TI - Gonadal preservation in a simple testicular cyst.
AB - The authors report a case of a simple testicular cyst in a 16-week-old infant.
Preoperative ultrasonography helped to diagnose this condition accurately.
Gonadal preservation and enucleation of testicular cysts are possible with a
careful surgical approach, and orchiectomy is not necessary.
PMID- 9639644
TI - Infantile myofibromatosis: a rare presentation with intussusception.
AB - Infantile myofibromatosis (IM) is a distinct but rare clinicopathological entity
occurring in neonates and infants. It probably represents a rare soft-tissue
tumour made up of undifferentiated myofibroblasts. Its recognition is important
since it can be mistaken for a malignancy when, in fact, it has a generally
benign prognosis with spontaneous regression. We describe the first case of an
infant with IM presenting with acute intussusception due to gastrointestinal as
well as the typical skin involvement.
PMID- 9639645
TI - Median nerve compression in Proteus syndrome.
AB - Proteus syndrome is a multi-organ disorder, a prime feature of which is localized
gigantism, usually clinically obvious. Symptoms secondary to hypertrophy of
nerves has not been previously recognized as a part of the syndrome.
PMID- 9639646
TI - Experience with a new technique of primary gastrostomy button placement in
association with the Nissen fundoplication.
AB - The tube gastrostomy has always been associated with significant morbidity,
mainly because of difficulty in immobilisation, resultant dislodgement, and
problems with replacement. Between January and October 1994, we employed a method
of primary button gastrostomy in 18 patients with excellent results.
Complications have been minimal. There has been no incidence of intra-peritoneal
gastric leakage, wound infection, or button dislodgement. Two patients have had
peristomal ulceration.
PMID- 9639647
TI - Open gastrostomy performed through the umbilicus.
AB - A new variation of open gastrostomy placement is described in which a Stamm
gastrostomy is performed via a supraumbilical incision around the circumference
of the umbilicus. Access to the stomach is good and the cosmetic result is
superior to that obtained with the conventional incision.
PMID- 9639648
TI - Deflating proximal enterostomy for jejunoileal atresia.
AB - A modification is described to avoid postoperative gaseous distension and
facilitate early oral feeding after resection and anastomosis for jejunoileal
atresia.
PMID- 9639649
TI - Venous access via the renal vein: a technical innovation.
AB - A patient with difficult venous access is described in whom both haemodialysis
and parenteral nutrition were required. To minimize the impact on transplant
prospects, the renal veins were used for vascular access. The technique and
rationale for this novel approach are presented.
PMID- 9639650
TI - Scroto-peritoneal port for laparoscopic orchidopexy.
AB - Recently, laparoscopic orchidopexy has been accepted as the standard procedure of
management for clinically impalpable testes. However, many techniques have been
described for the delivery of the mobilized testes. In this report, a new
approach is described. The use of a fourth "scroto-peritoneal" port, makes
complete laparoscopic orchidopexy possible, and in addition, is safe and easy to
perform.
PMID- 9639651
TI - Hepatobiliary cystadenoma with hyaline stroma.
PMID- 9639652
TI - Dictyostelium discoideum Hsp32 is a resident nucleolar heat-shock protein.
AB - Hsp32 is a small shock protein in Dictyostelium discoideum that is expressed in
growing cells in the absence of heat shock. Here we show that Hsp32 is an Ag-NOR
staining protein capable of binding DNA with high affinity. Hsp32 is also shown
to be a resident nucleolar protein both under normal growth conditions and during
heat stress. In unstressed cells, Hsp32 localizes to the nucleolar periphery in a
pattern reminiscent of the rDNA in this organism. During the first several hours
of heat shock, the peripheral localization of Hsp32 is not altered, although rDNA
transcription is arrested. Prolonged heat shock causes a condensation of the
rDNA. Under these conditions, Hsp32 is no longer predominantly associated with
the rDNA, but is instead distributed over the entire nucleolus. Hsp32 therefore
retains ist nucleolar localization under prolonged heat shock conditions by
associating with nucleolar components other than the rDNA or rRNA.
PMID- 9639653
TI - Remodeling of chromatin loops does not account for specification of replication
origins during Xenopus development.
AB - We have investigated the possible relationship between replicons and chromatin
loops during Xenopus development. In early embryos, replication of the ribosomal
RNA genes (rDNA) can initiate at apparently any sequence. Nevertheless, the need
for a regular spacing of replication origins suggests that some periodic
chromatin folding might dictate which sites are actually used for initiation.
After the midblastula transition, replication initiation is restricted to the
rDNA intergenic spacers. A remodeling of chromatin folding could account for this
change in origin usage. Here, it is reported that nuclear matrix anchorage of the
Xenopus rDNA occurs at multiple, apparently random sequences, throughout
embryonic development as well as in adult cells. In vitro matrix rebinding assays
confirmed the lack of specific anchoring sequences in the rDNA, before as well as
after specific replication origins are established. Thus, no change in loop
attachment sites could explain the change in origin usage at this locus.
Nonspecific loop anchorage was a special feature of the rDNA locus, since the
same nuclear matrices were able selectively to bind the scaffold attachment
region (SAR) of the Drosophila histone gene cluster in vitro. Blastula and
gastrula nuclear matrices bound a higher amount of SAR sequences than matrices
from later stages or adult cells. This developmental change in SAR binding might
explain the increase in size of the bulk of genomic DNA loops that occurs after
the gastrula stage. However, no change in chromatin loop organization that could
explain the midblastula stage transition from small to large replicons was
observed.
PMID- 9639654
TI - Centromeric genotyping and direct analysis of nondisjunction in humans: Down
syndrome.
AB - In species with chiasmate meioses, alterations in genetic recombination are an
important correlate of nondisjunction. In general, these alterations fall into
one of two categories: either homologous chromosomes fail to pair and/or
recombine at meiosis I, or they are united by chiasmata that are suboptimally
positioned. Recent studies of human nondisjunction suggest that these
relationships apply to our species as well. However, methodological limitations
in human genetic mapping have made it difficult to determine whether the
important determinant(s) in human nondisjunction is absent recombination, altered
recombination, or both. In the present report, we describe somatic cell hybrid
studies of chromosome 21 nondisjunction aimed at overcoming this limitation. By
using hybrids to "capture" individual chromosomes 21 of the proband and parent of
origin of trisomy, it is possible to identify complementary recombinant meiotic
products, and thereby to uncover crossovers that cannot be detected by
conventional mapping methods. In the present report, we summarize studies of 23
cases. Our results indicate that recombination in proximal 21q is infrequent in
trisomy-generating meioses and that, in a proportion of the meioses,
recombination does not occur anywhere on 21q. Thus, our observations indicate
that failure to recombine is responsible for a proportion of trisomy 21 cases.
PMID- 9639655
TI - Ordered arrangement and rearrangement of chromosomes during spermatogenesis in
two species of planarians (Plathelminthes).
AB - The pattern of distribution of telomeric DNA (TTAGGG), 28S rDNA, and 5S rDNA has
been studied using fluorescence in situ hybridization (FISH) and primed in situ
labelling during spermatogenesis and sperm formation in the filiform spermatozoa
of two species of planarians, Dendrocoelum lacteum and Polycelis tenuis
(Turbellaria, Plathelminthes). In both species, the positions of FISH signals
found with each probe sequence are constant from cell to cell in the nuclei of
mature sperm. Chromosome regions containing 5S and 28S rDNA genes are gathered in
distinct bundles of spiral form. In early spermatids with roundish nuclei, the
sites of a given sequence on different chromosomes remain separate. Centromeres
(marked by 5S rDNA) gather into a single cluster in the central region of the
slightly elongated sperm nucleus. During spermatid maturation, this cluster
migrates to the distal pole of the nucleus. In Polycelis, telomeric sites gather
into three distinct clusters at both ends and in the middle of the moderately
elongated nucleus. These clusters retain their relative positions as the
spermatid matures. All the chromosome ends bearing 28S rDNA gather only into the
proximal cluster. Our data suggest that structures in the nucleus selectively
recognise chromosome regions containing specific DNA sequences, which helps these
regions to find their regular places in the mature sperm nucleus and causes
clustering of the sites of these sequences located on different chromosomes. This
hypothesis is supported by observations on elongated sperm of other animals in
which a correlation exists between ordered arrangement of chromosomes in the
mature sperm nucleus and clustering of sites of the same sequence from different
chromosomes during spermiogenesis.
PMID- 9639656
TI - Unordered arrangement of chromosomes in the nuclei of chicken spermatozoa.
AB - The arrangement of chromosomes in the elongated sperm nuclei of chicken was
studied using fluorescence in situ hybridization with probes specific for
telomeres of all chromosomes, a microchromosome, the long arm of chromosome 6,
the large heterochromatic block on the Z-chromosome, and the same heterochromatic
block plus subtelomeric sites on macrochromosomes 1-4. The positions of all
probes vary from one sperm to another. No order in chromosome arrangement is
apparent. It is suggested that large chromosome size and small chromosome number
correlate with constant positions of chromosomes and vice versa. Based on the
known quantity of repetitive units of the repeat on the Z-chromosome, the degree
of compaction of chromatin in the chicken sperm nucleus is estimated as ca 0.7
Mb/ microm. As judged from the length of the heterochromatic region of the Z
chromosome at the lampbrush stage, the total length of the Z-chromosome in mature
sperm is 2.5-4 times that of the sperm nucleus.
PMID- 9639658
TI - Improved detection and comparative sizing of human chromosomal telomeres in situ.
AB - Telomeric length dynamics are thought to play an important role both in the
processes of cellular aging and cancer progression. We have revised the primed in
situ (PRINS) labeling technique to allow an estimation of the relative length of
individual telomeres. We illustrate the applicability of the approach by
demonstrating different telomeric sizes not only between blood lymphocytes from a
young and an old donor, but also among bone marrow cells from hematological
cancer patients. In the latter case we found general variations in telomeric
sizes as well as individual telomeric variations that would have escaped
detection by other methods. An interesting finding was the selective expansion of
a single telomere within a specific subset of cells.
PMID- 9639657
TI - CENP-G: a new centromeric protein that is associated with the alpha-1 satellite
DNA subfamily.
AB - A new constitutive centromere-specific protein (CENP) has been identified as a
result of its recognition as an autoantigen by serum from a patient with gastric
antral vascular ectasia disease. Conventional immunoblotting and two-dimensional
double blotting with both this antiserum and a known anti-centromere antiserum
showed that this antiserum predominantly recognized a Mr 95,000 protein that is
different from all known CENPs. We have named this new protein CENP-G. This
protein was detected at the centromeric region throughout the cell cycle. In
mitosis, it was restricted to the kinetochore inner plate as shown by immunogold
labeling and electron microscopy. The centromeres of some human chromosomes are
known to contain two subfamilies of alpha-satellite DNA. Using immunofluorescence
combined with fluorescent in situ hybridization with subfamily-specific DNA
probes, we revealed that CENP-G was specifically associated with one of the
subfamilies, which we have named alpha-1, but not the other. The localization and
the alpha-1-specific association suggested that CENP-G may play a role in
kinetochore organization and function. Like CENP-B and C, but unlike CENP-A, this
protein remained with the nuclear matrix after intensive extraction. While CENP-B
is absent from the human Y chromosome, the existence of CENP-G on the Y
chromosome has been proven by immunofluorescence and whole chromosome painting.
CENP-G was also detected in CHO, Indian muntjac and Chinese muntjac cells,
suggesting that it is conserved in evolution.
PMID- 9639659
TI - Sex chromosome linkage of chicken and duck type I interferon genes: further
evidence of evolutionary conservation of the Z chromosome in birds.
AB - Type I interferons (IFNs) are a family of proteins that are predominantly
expressed in response to viral infection. Two serologically distinct forms of
type I IFN, designated ChIFN1 and ChIFN2, have recently been recognized in the
chicken. ChIFN1 is encoded by a cluster of ten or more intronless genes, whereas
ChIFN2, whose primary sequence is 57% identical, is encoded by a single
intronless gene. By fluorescence in situ hybridization we now demonstrate that
the genes for ChIFN1 and ChIFN2 are all located on the short arm of the chicken Z
chromosome. This assignment was confirmed by results that showed that DNA from
male (ZZ) chickens yielded approximately twofold stronger Southern blot signals
with ChIFN1 and ChIFN2 hybridization probes than DNA from females (ZW). Attempts
to determine differences in IFN production between male and female chickens
failed owing to a high degree of variation in virus-induced IFN expression
between individuals of both sexes. Sex linkage of IFN genes was also observed in
domestic ducks: fluorescence in situ hybridization of duck metaphase chromosomes
with a duck type I IFN probe was confined to the terminal region of the long arm
of the Z chromosome. Thus, in contrast to mammals, which have their IFN genes on
autosomes, birds have the type I IFN genes on the sex chromosome.
PMID- 9639660
TI - Two separate conserved domains of eukaryotic DNA topoisomerase I bind to each
other and reconstitute enzymatic activity.
AB - The two-hybrid system was used to identify proteins that interact with the
central conserved domain of Saccharomyces cerevisiae DNA topoisomerase I. Several
different C-terminal domain-containing fragments of topoisomerase I, none of
which overlapped with the central domain, were identified as specific interacting
polypeptides. Coexpression of these two domains in yeast partially complemented
the growth defects of top1-top2ts and top1-hpr1 mutants. Moreover, an in vitro
assay showed that some topoisomerase I enzymatic activity was restored to these
mutants. The results demonstrate that the central domain of topoisomerase I
interacts with the C-terminal domain of the protein and that these two domains
reconstitute enzymatic activity in vivo, even when expressed as separate
polypeptides.
PMID- 9639661
TI - Growth promotion by homocysteine but not by homocysteic acid: a role for
excessive growth in homocystinuria or proliferation in hyperhomocysteinemia?
AB - Excessive growth of long bones in patients with homocystinuria is still
unexplained and previous work incriminating homocysteic acid could not be
confirmed by others. In vitro studies from our laboratory showed that
homocysteine stimulated growth in a clonogenic assay. This observation made us
study plasma cyclin dependent kinase (CDK), homocyst(e)ine and homocysteic acid
in 10 patients with homocystinuria and 20 controls. In addition, homocysteine and
homocysteic acid were tested in a clonogenic assay to correlate the growth
promoting activity with CDK. Plasma CDK (protein) correlated strongly with
homocysteine (r=0.84) but not with homocysteic acid. Supernatants of the
clonogenic assay samples showed up to three times higher CDK levels in the
presence of homocyst(e)ine but not homocysteic acid. In vitro data and the strong
correlation between homocysteine and CDK suggest a role for homocysteine
stimulating CDK, the starter of mitosis, with subsequent stimulation of growth.
PMID- 9639662
TI - Increased transcription decreases the spontaneous mutation rate at the thymidine
kinase locus in human cells.
AB - Transcription increases DNA repair efficiency and modulates the distribution of
certain types of DNA damage. Furthermore, increased transcription level
stimulates spontaneous mutation rate in yeast. We explored whether transcription
level affects spontaneous mutation rate in human cells. We first developed two
thymidine kinase (tk) inducible human cell lines using the Gal4-Estrogen receptor
system. In our TK6i-G3 and G9 tk heterozygous cell lines, the active tk allele is
linked to an inducible promoter element. Tk mRNA is induced following treatment
with estrogen. Spontaneous mutation rate was significantly decreased in human
cell lines after induction in contrast to the report in yeast. Thus, humans may
have evolved different or additional mechanisms to deal with transcription
related spontaneous mutagenesis.
PMID- 9639663
TI - The role of neuronal growth factors in neurodegenerative disorders of the human
brain.
AB - Recent evidence suggests that neurotrophic factors that promote the survival or
differentiation of developing neurons may also protect mature neurons from
neuronal atrophy in the degenerating human brain. Furthermore, it has been
proposed that the pathogenesis of human neurodegenerative disorders may be due to
an alteration in neurotrophic factor and/or trk receptor levels. The use of
neurotrophic factors as therapeutic agents is a novel approach aimed at restoring
and maintaining neuronal function in the central nervous system (CNS). Research
is currently being undertaken to determine potential mechanisms to deliver
neurotrophic factors to selectively vulnerable regions of the CNS. However, while
there is widespread interest in the use of neurotrophic factors to prevent and/or
reduce the neuronal cell loss and atrophy observed in neurodegenerative
disorders, little research has been performed examining the expression and
functional role of these factors in the normal and diseased human brain. This
review will discuss recent studies and examine the role members of the nerve
growth factor family (NGF, BDNF and NT-3) and trk receptors as well as additional
growth factors (GDNF, TGF-alpha and IGF-I) may play in neurodegenerative
disorders of the human brain.
PMID- 9639664
TI - Phospholipase D activity is altered in X-linked adrenoleukodystrophy heterozygous
carriers, but not in hemizygous patients.
AB - Abnormalities in levels of choline and its metabolites have been reported in the
lesions of brains of X-linked adrenoleukodystrophy (X-ALD) patients. We have
examined the turnover of the major choline-containing phospholipid,
phosphatidylcholine (PtdCho), in fibroblasts from hemizygous X-ALD, heterozygous
X-ALD, Zellweger syndrome (ZW), and male and female control individuals to assess
possible alterations in PtdCho metabolism mediated by activation of protein
kinase C (PKC). Hydrolysis of PtdCho by phospholipase D (PLD) and resynthesis of
PtdCho from labeled choline were stimulated 2- to 4-fold by PKC activation with
the phorbol ester, 4beta-12-O-tetradecanoylphorbol-13-acetate (beta-TPA), in all
cells except those from heterozygous X-ALD individuals. No differences in
quantity or intracellular distribution of PKC activity, PKC isoforms by Western
blot analysis, or of the PKC substrate, myristoylated alanine-rich C kinase
substrate (MARCKS), were apparent in any of the cells. Thus, altered PtdCho
metabolism was not directly linked to either of these inherited defects that
result in abnormal peroxisomal functions. Further, altered responsiveness of PLD
in X-ALD heterozygotes was independent of changes in PKC and MARCKS.
PMID- 9639665
TI - Utilization of microhomologous recombination in yeast to generate targeting
constructs for mammalian genes.
AB - We have developed a new procedure utilizing microhomologous recombination in
yeast to generate targeting constructs for producing targeted mutations in mice.
This procedure is rapid and efficient, and should be directly applicable to all
mammalian genes. Moreover, only minimal information about the locus being
targeted is required. The feasibility of this approach was demonstrated by
producing another allele of the mouse Tg737 polycystic kidney gene.
PMID- 9639666
TI - Role of intracellular second messengers and reactive oxygen species in the
pathophysiology of V. cholera O139 treated rabbit ileum.
AB - Vibrio cholerae O139 has pandemic potential and it produces copious amounts of
fluid secretion. The levels of various second messengers (intracellular Ca2+,
cAMP, IP3, PKC) were measured to determine the cause of fluid secretion produced
by this strain of V. cholerae. There was a significant increase in the levels of
these second messengers in V. cholerae O139 treated ileum as compared to control
ileum (enterocytes). Levels of these second messengers were also assessed in V.
cholerae 569B induced fluid secretion in rabbit ileum and it was found that the
levels were raised more in V. cholerae O139 treated ileum than in V. cholerae
569B treated rabbit ileum. The intestinal damage was assessed by measuring
changes in the extent of lipid peroxidation of the enterocytes. Intracellular
second messengers are known to raise the extent of lipid peroxidation. In V.
cholerae O139 treated loops calcium ionophore A23187 enhanced the extent of lipid
peroxidation whereas l-verapamil could only marginally decrease the lipid
peroxidation. Dantrolene and H7 significantly decreased the extent of lipid
peroxidation of enterocytes in V. cholerae O139 treated rabbit ileum. However,
PMA could not enhance further the extent of lipid peroxidation in V. cholerae
O139 treated rabbit ileum. So intracellular calcium and protein kinase C appear
to be involved in intestinal damage caused by V. cholerae O139. Reactive oxygen
species are responsible for causing tissue damage and the extent of oxidative
damage depends on the balance between the pro-oxidants and the anti-oxidants. So
the changes in the enterocytes' antioxidant level during V. cholerae O139
mediated intestinal infection was estimated. There was a significant decrease in
the enterocyte level of the antioxidant enzymes SOD, catalase, glutathione
peroxidase, glutathione reductase, glutathione transferase and glucose-6
phosphate dehydrogenase in V. cholerae O139 mediated intestinal infection. So a
significant decrease in the levels of antioxidant defenses and a significant
increase in the levels of second messengers appear to be important in mediating
V. cholerae O139 induced lipid peroxidation which contributes to the changes in
membrane permeability and thus to fluid secretion.
PMID- 9639667
TI - Caffeine does not potentiate gamma-radiation induced DNA damage in ataxia
telangiectasia lymphoblastoid cells.
AB - Ataxia telangiectasia (AT) cells display a profound sensitivity to ionizing
radiation, exhibiting more frequent chromosomal breaks, increased micronuclei
formation and abnormal DNA repair kinetics following exposure. Despite the recent
cloning of the ATM gene there remains a need for a simple and rapid means of
discriminating AT heterozygotes from normal individuals. Caffeine (1,3,7
trimethyl xanthine), known to inhibit the repair of double-strand DNA breaks
following ionizing radiation, increases the frequency of radiation induced
chromosomal breaks in normal cells. Here we report that caffeine potentiates the
induction of chromosomal breaks in G2 arrested AT heterozygote and normal
lymphoblastoid cells, but not in homozygous AT lymphoblastoid cells. This
observation parallels the findings reported by others that caffeine fails to
potentiate the effect of ionizing radiation in radiation-sensitive yeast strains
and radiation sensitive CHO cells. It also suggests that caffeine may somehow
mimic the effect of the ATM gene product in normal cells. We also report that
caffeine is unlikely to be useful in helping to discriminate AT heterozygotes
from normal individuals.
PMID- 9639668
TI - Antimicrobial peptides derived from pepsinogens in the stomach of the bullfrog,
Rana catesbeiana.
AB - Three antimicrobial peptides, which had strong antimicrobial activity against a
broad spectrum of microorganisms, were isolated from the stomach of the bullfrog,
Rana catesbeiana. Two of the antimicrobial peptides were found to be derived from
the N-terminal sequences of pepsinogen A and C prosequences. The amino acid
sequences of the new antimicrobial peptides, named bullfrog pepsinogen A-derived
antimicrobial peptide (bPaAP) and bullfrog pepsinogen C-derived antimicrobial
peptide (bPcAP), were Gly-Val-Val-Lys-Val-Ser-Arg-Leu-Lys-Gly-Glu-Ser-Leu-Arg-Ala
Arg-Leu (MW 1865.5) and Ile-Ile-Lys-Val-Pro-Leu-Lys-Lys-Phe-Lys-Ser-Met-Arg-Glu
Val-Met-Arg-A sp-His-Gly-Ile-Lys-Ala-Pro-Val-Val-Asp-Pro-Ala-Thr-Lys-Tyr (MW
3691.6), respectively. The bPaAP and bPcAP adopted 35% and 42% amphipathic alpha
helical structure in 50% trifluoroethanol, respectively, and were non-hemolytic
up to a concentration of 200 microg/ml. Synthesized pepsinogen C prosequences of
monkey and human, which had similar structural characteristics as bPaAP and
bPcAP, also showed antimicrobial activity at concentrations of 10-200 microg/ml.
The third peptide was buforin I, previously found in the stomach of the Asian
toad, Bufo bufo gargarizans. These findings strongly suggest that peptides
derived from the prosequences of pepsinogens, along with buforin I, may
contribute to the antimicrobial function of the gastrointestinal mucosa of
vertebrates, including human.
PMID- 9639669
TI - A method to score micronuclei in vivo using cytochalasin B-induced cytokinesis
block.
AB - The present paper describes an in vivo micronucleus assay using Cytochalasin B
(CyB). Mice bearing three different tumours, fibrosarcoma (Swiss albino mice),
B16 F1 melanoma (C57 BL) and Ehrlich ascites carcinoma (Swiss albino mice), were
injected with repeated doses of CyB at different time intervals and binucleate
cells were scored at 24, 36, 48, 60 and 72 h after CyB injection. It was found
that three doses of 3+2+2 mg/kg CyB administered intraperitoneally (i.p.) at 12-h
intervals effectively blocked cytokinesis. The maximum number of binucleated
cells (BNC) was scored at 60 h after the last CyB dose. This dose schedule was
also effective in scoring micronuclei in BNC after irradiation.
PMID- 9639671
TI - The functions of the preplate in development and evolution of the neocortex and
hippocampus.
AB - Recently, it has been shown that the early developmental organization of the
archicortical hippocampus resembles that of the neocortex. In both cortices at
embryonic stages, a preplate is present, which is split by the formation of the
cortical plate into a marginal zone and a subplate layer. The pioneer neurons of
the preplate are believed to form a phylogenetically ancient cortical structure.
Neurons in these preplate layers are the first postmitotic neurons and have
important roles in the development of the cerebral cortex. Cajal-Retzius cells in
the marginal zone regulate the phenotype of radial glial cells and may direct
neuronal migration establishing the inside-out gradient of corticogenesis.
Furthermore, pioneer neurons form the initial axonal connections with other
(sub)cortical structures. A significant difference between the hippocampus and
neocortex, however, is that in the hippocampus, most afferents are guided by the
pioneer neurons in the prominent marginal zone, while in the neocortex most
ingrowing afferent axons enter via the subplate. At later developmental periods,
most pioneer neurons disappear by cell death or transform into other neuronal
shapes. Here, we review the early developmental organization of the mammalian
cerebral cortex (both neocortex and hippocampus) and discuss the functions and
fate of pioneer neurons in cortical development, in particular that of Cajal
Retzius cells. Evaluating the developmental properties of the hippocampus and
neocortex, we present the hypothesis that the distribution of the main ingrowing
afferent systems in the developing neocortex, which differs from the one in the
hippocampal region, may have enabled the specific evolution of the neocortex.
PMID- 9639670
TI - Fewer chromosome aberrations and earlier apoptosis induced by DNA synthesis
inhibitors, a topoisomerase II inhibitor or alkylating agents in human cells with
normal compared with mutant p53.
AB - The human lymphoblastoid cell lines TK6 (normal p53) and WI-L2-NS or WTK1 (mutant
p53) differ in sensitivity to killing and induction of gene mutations and
chromosome aberrations by ionizing radiation. This may be related to decreased
apoptosis in the cells with mutated p53, such that more damaged cells survive. We
compared the response of the two cell types to various chemicals. First, to
ensure that the thymidine kinase deficiency does not increase the sensitivity of
TK6 tk+/- cells to mutagens, we demonstrated that they were not hypersensitive to
aberration induction by altered DNA precursor pools or DNA synthesis inhibition,
by aphidicolin (APC), methotrexate, hydroxyurea (HU), cytosine arabinoside and
thymidine. TK6 cells were then compared with WI-L2-NS or WTK1 cells. With APC,
HU, methyl methanesulfonate (MMS), ethyl nitrosourea (ENU) and etoposide (etop),
TK6 cells had more apoptosis in the first two days after treatment. Fewer
aberrations were seen in normal p53 TK6 cells than the mutant p53 WI-L2-NS cells,
ranging from very little difference between the two cell types with MMS to very
large differences with ENU and etop. For MMS and ENU we followed cultures for
several days, and found that WI-L2-NS cells underwent delayed apoptosis 3 to 5
days after treatment, in parallel with published observations with ionizing
radiation. WI-L2-NS cells also had a delayed increase in aberrations (up to 5
days post-treatment) when no aberrations remained in TK6 cells. Colony forming
efficiency was measured for APC, MMS and ENU, and was greater in the p53 mutant
cells. Our results show that normal p53 function is required for rapid and
efficient apoptosis in these lymphoblastoid cells with DNA synthesis inhibitors,
alkylating agents and a topoisomerase II inhibitor, and support the hypothesis
that induced levels of aberrations are higher in p53 mutant cells because of a
failure to remove damaged cells by apoptosis.
PMID- 9639672
TI - Coding defect and a TATA box mutation at the bilirubin UDP
glucuronosyltransferase gene cause Crigler-Najjar type I disease.
AB - Mutations at the bilirubin UDP-glucuronosyltransferase (transferase) gene in a
severely hyperbilirubinemic Crigler-Najjar (CN) type I individual was compared
with that in a moderately hyperbilirubinemic CN II individual. The CN-I (CF)
patient in this study sustained a TATA box insertional mutation which was paired
with a coding defect at the second allele, unlike all coding defects previously
seen in CN-I patients. The sequence of the mutant TATA box, [A(TA)8A], also seen
in the CN-II patient, was compared with that at the wild-type box, [A(TA)7A].
Transcriptional activity with [A(TA)8A] was 10-15% that with the wild-type box
when present in the -1.7 kb upstream regulatory region (URR) of the bilirubin
transferase UGT1A1 gene which was fused to the chloramphenicol acetyl transferase
reporter gene, pCAT 1.7H, and transfected into HepG2 cells. Also, a construct
with a TA deletion, [A(TA)6A], was prepared and used as a control;
transcriptional activity was 65% normal. The coding region defect, R336W, seen in
CF (CN-I) was placed in the bilirubin transferase UGT1A1 [HUG-Br1] cDNA, and its
corresponding protein was designated UGT1A1*32. The UGT1A1*32 protein supported 0
10% normal bilirubin glucuronidation when expressed in COS-1 cells. The I294T
coding defect seen at the second allele in SM (CN-II) generated the UGT1A1*33
mutant protein which supported 40-55% normal activity with a normal Km (2.5
microM) for bilirubin. The hyperbilirubinemia seen in SM decreased in response to
phenobarbital treatment, unlike that seen in CF. Parents of the patients were
carriers of the respective mutations uncovered in the offspring. The TATA box
mutation paired with a deleterious missense mutation is, therefore, completely
repressive in the CN-I patient, and is responsible for a lethal
genotype/phenotype; but when homozygous, i.e. paired with itself, as previously
reported in the literature, it is far less repressive and generates the mild
Gilbert's phenotype.
PMID- 9639673
TI - The form of iron oxide deposits in thalassemic tissues varies between different
groups of patients: a comparison between Thai beta-thalassemia/hemoglobin E
patients and Australian beta-thalassemia patients.
AB - Mossbauer spectra of 12 beta-thalassemia/hemoglobin E spleen samples from Thai
patients who had not received multiple blood transfusions and chelation therapy
and seven beta-thalassemia spleen samples from Australian patients who had
received multiple blood transfusions and chelation therapy were recorded with
sample temperatures of 78 K. Each spectrum was found to consist of a
superposition of a relatively intense central doublet characteristic of high-spin
Fe(III), a low intensity sextet of peaks due to magnetic hyperfine-field
splitting, and occasionally a doublet that could be attributed to heme iron. A
significant (P=0.01) difference (Kolmogorov-Smirnov statistic of 0.71) between
the distributions of sextet signal intensity as a fraction (Fs) of the total non
heme iron Mossbauer spectral signal for the two groups of patients was detected.
The distribution of Fs for the Thai beta-thalassemia/hemoglobin E spleens had a
mean value of 0.128 (S.D. 0.035) while that for the Australian beta-thalassemia
spleens had a mean of 0.27 (S.D. 0.12). No significant difference between the
distributions of non-heme iron concentrations in the tissues for the two groups
of patients was detected by atomic absorption spectrometry. This study shows that
the Australian beta-thalassemia patients had a higher fraction of their non-heme
spleen iron in a goethite-like form than the Thai beta-thalassemia/Hb E patients.
PMID- 9639674
TI - DNA damage and cytotoxicity induced by beta-lapachone: relation to poly(ADP
ribose) polymerase inhibition.
AB - beta-Lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5, 6-dione) was
previously shown to enhance the lethality of X-rays and radiomimetic agents and
its radiosensitizing role in mammalian cells was attributed to a possible
interference with topoisomerase I activity. Furthermore, beta-lapachone alone was
found to induce chromosomal damage in Chinese hamster ovary (CHO) cells. The aim
of the present study was to further elucidate the possible mechanisms by which
beta-lapachone exerts its genotoxic action in cultured mammalian cells. Flow
cytometry analysis of beta-lapachone-treated CHO cells indicated a selective
cytotoxic effect upon S phase of the cell cycle. beta-lapachone produced DNA
strand breaks as determined by alkaline elution assay; alkaline elution profiles
from treated cells showed a bimodal dose-response pattern, with a threshold dose
above which a massive dose-independent DNA degradation was observed. Furthermore,
beta-lapachone increased the capacity of crude CHO cellular extracts to unwind
supercoiled plasmid DNA, while significantly inhibiting in vitro poly(ADP-ribose)
polymerase (PARP). These results suggest that damage induction is probably
mediated by the interaction between beta-lapachone and cellular enzymatic
function(s), rather than reflecting a direct action on the DNA. We suggest that
the inhibition of PARP plays a central role in the complex biological effects
induced by beta-lapachone in CHO cells.
PMID- 9639675
TI - Neuroleptic drug-stimulated iron uptake by synaptosome preparations of rat
cerebral cortex.
AB - Neuroleptic-induced tardive dyskinesia has been linked to impaired iron
homeostasis in the central nervous system attributed to increased iron levels. A
chlorpromazine stimulatory effect upon iron uptake from 55Fe-citrate and 55Fe
transferrin by cortical synaptosome preparations of rats was recently
demonstrated. The present work extends this study to other neuroleptic drugs such
as thioridazine, haloperidol, clozapine and fluphenazine. Like chlorpromazine,
thioridazine showed a stimulatory effect upon iron uptake from both iron donors
whereas fluphenazine highly increased uptake from 55Fe-citrate but not from 55Fe
transferrin. Haloperidol and clozapine had no effect. Stimulation of iron uptake
by neuroleptics is probably related to their property of calmodulin antagonism,
since calmidazolium also stimulated synaptosomal iron uptake from both donors.
Calmidazolium-stimulated uptake from 55Fe-citrate was approx. 5-fold when
compared to control samples while uptake from 55Fe-transferrin was 250% higher.
The results are in agreement with the iron uptake magnitude observed with the
different drugs for the two iron donors used and the reported Ki values of
neuroleptic drugs for calmodulin antagonism evaluated by the inhibition of 3',5'
monophosphate phosphodiesterase activity. Moreover, vanadate, an inhibitor of
protein phosphorylation and KCl-promoted membrane depolarization, greatly
inhibited iron uptake from 55Fe-citrate by both chlorpromazine-treated and
untreated synaptosome preparations.
PMID- 9639676
TI - Chromosome abnormalities in peripheral blood lymphocytes from Cebus apella
(Cebidae, Platyrrhini) after X-ray irradiation.
AB - In this paper, we describe the results of a qualitative and quantitative study of
chromosomal reorganizations observed in X-irradiated (1Gy and 2Gy) and cultured
lymphocytes from Cebus apella. A total of 646 breakpoints have been detected,
identified and localized in the ideogram of the species. The breakpoint
distribution along chromosomes, p and q arms, and bands is not random.
Chromosomes #11, #12 and chromosome arms 1p, 12p, 13p, 15p, 11q, and 12q are
significantly more affected than expected, while chromosome #19 and chromosome
arm 19q are less affected. Terminal regions of chromosome arms accumulate a
higher number of breakpoints than the rest of the chromosome (37.82%). A high
percentage (93.66%) of breakpoints is found in G negative bands.
PMID- 9639677
TI - Pattern generation for stick insect walking movements--multisensory control of a
locomotor program.
PMID- 9639678
TI - Presenilin-1 mutations associated with familial Alzheimer's disease do not
disrupt protein transport from the endoplasmic reticulum to the Golgi apparatus.
AB - Mutations in genes encoding presenilin-1 (PS1) and presenilin-2 (PS2) have been
linked to familial forms of Alzheimer's disease (AD). Cells expressing mutant
presenilins produce elevated levels of Abeta42, the major amyloid peptide found
in AD plaques. The mechanism whereby this occurs remains unknown, but the
localization of presenilins to endoplasmic reticulum (ER) and Golgi compartments
has suggested that they may function in intracellular trafficking pathways
involved in processing beta-amyloid precursor proteins (APP). To test this
possibility, we coexpressed PS1(wt), PS1(M146L), or PS1(L286V) in HEK293 cells
together with the LDL receptor, a classic glycoprotein marker that undergoes post
translational O-glycosylation in the Golgi compartment. Pulse-chase analysis of
the receptor indicated that mutant presenilins had no effect on ER-->Golgi
transport. Similar results were obtained when the studies were carried out with
cells expressing the Swedish variant of APP (SWAPP751) instead of the LDL
receptor. Moreover, secretion of the soluble exodomain polypeptide fragments of
SWAPP751 that arise from alpha-secretase and beta-secretase cleavage was not
markedly affected by the PS1 mutants. Despite the lack of discernible effect of
the PS1 mutants on trafficking of proteins through the Golgi apparatus, they
caused a substantial increase in the proportion of Abeta42 relative to total
Abeta in the culture medium. The results suggest that mutant forms of PS1 cause
elevated production of Abeta42 by a mechanism that is independent of a major
disruption of exocytic trafficking of APP.
PMID- 9639679
TI - DNA damage caused by common cytological fixatives.
AB - Tissues from nine species of plants and fungi were treated separately with eight
solutions, including seven cytological fixatives (3.7% formaldehyde at pH 3.0 and
7.0, FAA at pH 3.0 and 7. 0, 1% glutaraldehyde at pH 3.0 and 7.0, and Lavdowsky's
fluid at pH 3.0) and one storage buffer (SED=NaCl-EDTA-DMSO, pH 7.0). DNA from
untreated tissue and SED-treated tissue was of high molecular weight (>50 kb).
DNA from glutaraldehyde-treated tissues averaged 20 kb in length, while DNA from
all other treatments averaged less than 8 kb in length. Each DNA was subjected to
amplification using the polymerase chain reaction, followed by sequencing of 250
bp near the 3' end of the nuclear rRNA small subunit gene. Glutaraldehyde
treatments (at pH 3.0 and 7.0) produced damaged bases at rates of 0. 0% to less
than 0.1%. Treatments with Lavdowsky's fluid (containing mercuric chloride), FAA
at pH 7.0, and SED produced rates of 0.0% to 3.6%. FAA at pH 3.0 produced rates
of 7.6% to 15.6%. Nearly 100 attempts to amplify from specimens treated with 3.7%
formaldehyde (at pH 3.0 and 7.0) failed, indicating extreme damage to the DNA.
PMID- 9639680
TI - Estrogen-induced tumorigenesis in the pituitary gland of TGF-beta(+/-) knockout
mice.
AB - Transforming growth factor (TGF)-beta receptor type II gene (Tgfbr2) knockout and
wild type mice underwent chronic estrogen exposure using estradiol pellets.
Histological examination of the pituitary glands found 38 adenomas in 14
Tgfbr2(+/-) mice but only one tumor in ten wild type mice. Pituitary
tumorigenesis is greatly accelerated in Tgfbr2(+/-) mice by estrogen treatment.
PMID- 9639681
TI - Assembly of a high-resolution map of the Acadian Usher syndrome region and
localization of the nuclear EF-hand acidic gene.
AB - Usher syndrome type 1C (USH1C) occurs in a small population of Acadian
descendants from southwestern Louisiana. Linkage and linkage disequilibrium
analyses localize USH1C to chromosome 11p between markers D11S1397 and D11S1888,
an interval of less than 680 kb. Here, we refine the USH1C linkage to a region
less than 400 kb, between genetic markers D11S1397 and D11S1890. Using 17 genetic
markers from this interval, we have isolated a contiguous set of 60 bacterial
artificial chromosomes (BACs) that span the USH1C critical region. Exon trapping
of BAC clones from this region resulted in the recovery of an exon of the nuclear
EF-hand acidic (NEFA) gene. However, DNA sequence analysis of the NEFA cDNA from
lymphocytes of affected individuals provided no evidence of mutation, making
structural mutations in the NEFA protein unlikely as the cellular cause of
Acadian Usher syndrome.
PMID- 9639682
TI - Similar mutational spectra in the HPRT gene of human and hamster cell lines after
exposure to either low dose rate or high dose rate X-rays.
AB - The dose rate at which cells are exposed to X-rays may influence the nature of
induced mutations. To investigate this, the molecular spectra were determined at
the HPRT gene in a hamster (V79) and a human (WI-L2-NS) cell line after the same
total dose of X-rays has been administered at either a low dose rate (LDR; 3.33
mGy/min) or a high dose rate (HDR; 1.24-1.4 Gy/min) X-irradiation. Mutational
spectra appeared similar, the fraction of mutants carrying deletions ranging
between 59%-66% for the V79 strain and between 64%-75% for the WI-L2-NS strain,
and independent of the irradiation conditions. The data indicate no effect of
ongoing repair processes under LDR conditions on the kind of induced mutations in
mammalian cells.
PMID- 9639683
TI - Human chondroitin 6-sulfotransferase: cloning, gene structure, and chromosomal
localization.
AB - Chondroitin 6-sulfotransferase (C6ST) is the key enzyme in the biosynthesis of
chondroitin 6-sulfate, a glycosaminoglycan implicated in chondrogenesis,
neoplasia, atherosclerosis, and other processes. C6ST catalyzes the transfer of
sulfate from 3'-phosphoadenosine 5'-phosphosulfate to carbon 6 of the N
acetylgalactosamine residues of chondroitin. Based on the previously published
avian sequence, we searched the database of expressed sequence tags (dbEST) and
obtained partial-length cDNAs that we completed by 5'-RACE using human
chondrosarcoma and endothelial-cell RNA as template. Stable transfection of our
full-length expression construct into CHO-K1 cells resulted in marked increases
in C6ST and keratan sulfate sulfotransferase (KSST) enzymatic activities in cell
homogenates. The predicted 411 amino acid sequence of human C6ST contains an N
terminal hydrophobic domain consistent with membrane insertion, four potential
sites for N-linked glycosylation, several consensus sequences for protein
phosphorylation, and one RGD sequence. The human and chick C6ST cDNA share 51%
nucleotide identity, 40% amino acyl identity, and 75% amino acyl conservation.
The human C6ST gene structure has been elucidated and exhibits an intron-less
coding region, and the gene has been mapped to human chromosome 11 by radiation
hybrid panel mapping.
PMID- 9639684
TI - New Escherichia coli WP2 tester strains highly sensitive to reversion by
oxidative mutagens.
AB - New Escherichia coli strains have been added to the WP2 mutagenicity test for the
specific detection of oxidative mutagens. Strain IC203 derives from WP2
uvrA/pKM101 and is highly sensitive to oxidative stress due to a deficiency in
the OxyR function. Following exposure to t-butyl hydroperoxide (BuOOH) or
menadione (MD), but not to 4-nitroquinoline 1-oxide (4NQO), strain IC203 (oxyR)
shows increased mutability with respect to the oxyR+ parent. The advantage that
the OxyR deficiency confers on IC203 strain in detecting oxidative mutagens is
not obtained with strains deficient in either katG or ahpCF, two OxyR-regulated
genes. Strain IC206, a derivative of WP2 uvrA carrying a deletion of the umuDC
genes and deficient in the MutY glycosylase, has also been added to the WP2 test
for the detection of SOS-independent mutations promoted by 8-oxoguanine lesions.
Induction of these mutations was observed after treatment with BuOOH, but not
after MD or 4NQO exposure. The two new strains, IC203 and IC206, can be useful
for the screening of mutations resulting from oxidative stress as well as in
studies on antioxidants preventing mutagenesis.
PMID- 9639685
TI - The in vivo mutagenicity and mutational spectrum at the lacI transgene recovered
from the spleens of B6C3F1 lacI transgenic mice following a 4-week inhalation
exposure to 1,3-butadiene.
AB - 1,3-Butadiene (BD) is carcinogenic and mutagenic in B6C3F1 mice. We determined
the lacI mutant frequency and mutational spectrum in spleen following inhalation
exposure to BD at levels that are known to induce tumors. B6C3F1 lacI transgenic
mice were exposed to air or to 62.5, 625, or 1250 ppm BD for 4 weeks (6 h/day, 5
days/week) and euthanized 14 days after the last exposure. BD increased the lacI
mutant frequency in spleen at all levels of BD examined. In BD-exposed mice, an
increased frequency of G:C-->A:T transitions occurred at non-5'-CpG-3' sites.
Exposure to BD in B6C3F1 lacI transgenic mice also increased the frequency of
base substitution mutations that occurred at A:T base pairs when compared to air
controls. The increased frequency of specific mutations at G:C base pairs in
spleen was not observed in our previous studies in bone marrow and indicates
tissue-specific differences in the BD-induced mutational spectrum. These data
demonstrate that in vivo transgenic mouse mutagenicity assays can identify tissue
specific mutagenicity and mutational spectrum responses of genotoxic carcinogens
at exposure levels that are known to induce tumors.
PMID- 9639686
TI - In vivo antigenotoxic effects of dietary agents and beverages co-administered
with urethane: assessment of the role of glutathione S-transferase activity.
AB - Antigenotoxic effects and changes in glutathione S-transferase (GST) activity
were assessed in mice after oral co-administration of urethane (URE) with aqueous
extracts of dietary vegetables (carrot, spinach and cabbage), spices (cinnamon,
pepper, cumin, clove and cardamom), tea and coffee. The results of the
genotoxicity assay (micronucleus test) demonstrated dose-related antigenotoxic
effects after URE was co-administered with aqueous extracts of vegetables,
spices, tea and coffee. Inhibition of GST activity was observed 4 h after
treatment with URE alone. Co-administration of URE with extracts of vegetables,
coffee and spices resulted in dose-related attenuation of the inhibitory effect
of URE on GST activity. However, tea had no effect on inhibition of GST activity
by URE. Hence an association between antigenotoxicity and GST activity could not
be established.
PMID- 9639687
TI - The alkaline single-cell gel electrophoresis (SCGE) assay applied to the analysis
of radiation-induced DNA damage in thyroid cancer patients treated with 131I.
AB - The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be
a promising tool for measuring DNA damage at the individual cell level in both in
vitro and in vivo studies. To provide further data on the possible applicability
of this assay in human biomonitoring studies, we have evaluated the eventual
genetic damage induced by therapeutic exposure to 131I, by measuring the Comet
length and the amount of DNA damage in peripheral blood leukocytes from a group
of 28 thyroid cancer patients who received 131I sodium iodide via oral
administration. Blood samples were taken just before the treatment and 1 week
after it. From the results obtained after radioiodine therapy, a small increase
in the Comet length and in the grade of DNA damage is observed; however, this
increase is not statistically significant because of inter-individual variability
and the variable responses before and after 131I treatment. Considering our
previous studies showing significant increases in the frequency of cytogenetic
damage (when measured as micronuclei) in patients treated with relatively low
doses of 131I, the results obtained in the present work by using the Comet assay
could indicate that 1 week after the exposure most of the radioiodine-induced DNA
lesions, that can be detected with this assay, have already been repaired.
PMID- 9639688
TI - Radioprotective effect of zinc aspartate on mouse spermatogenesis: a flow
cytometric evaluation.
AB - The radioprotective effect of zinc aspartate on spermatogonial cells of whole
body irradiated mice was studied using flow cytometry. Adult male Swiss albino
mice were treated with 30 mg/kg body weight of zinc aspartate 30 min before
exposure to 0, 0.5, 1, 2 and 3 Gy of gamma-radiation. The animals were killed 7
to 70 days postirradiation and the relative percentages of different germ cells
were analyzed by flow cytometry. A significant increase (p<0.002, 0. 0001, 0.005
and 0.008 for 0.5, 1, 2 and 3 Gy, respectively) in the relative percentage of
spermatogonial (2C) population was observed in mice treated with zinc aspartate
before exposure to different doses of gamma-radiation, compared to the irradiated
controls on day 35 posttreatment. Also mean of each radiation dose of all the
intervals studied showed a significant (p<0.03) increase in the relative
percentage of spermatogonia. Despite the increase in the relative percentage of
spermatogonia, the relative percentage of tetraploid cells (4C) remained higher
in the zinc aspartate treated mice, compared to the irradiated controls. However,
there was no change in the haploid populations viz. round (1C) and elongated (HC)
spermatids of the zinc aspartate pretreated animals compared to irradiated
controls. These data suggests that zinc aspartate pretreatment protects
spermatogonia and tetraploid cells from radiation-induced cell killing.
PMID- 9639689
TI - Genotoxicity of nitric oxide produced from sodium nitroprusside.
AB - Induction of mutation and micronucleus (MN) formation by nitric oxide (NO) was
investigated in mammalian cells using sodium nitroprusside (SNP) as a drug donor
of NO. Results showed that the concentration of NO2- in the tested solution rose
according to time- and concentration-exposure to SNP. The treatment of SNP (0.5-8
micromol/ml with S9 or 2-8 micromol/ml without S9) induced a concentration
dependent increase in the mutation frequency at the gpt gene locus in g12 cells
and caused a 13- (-S9) to 25- (+S9) fold increase above the background level at
the highest concentration. A statistically significant increase in the number of
micronucleated binucleated cells (MNBN) was also observed in treated groups. MNBN
per thousand, MN per thousand and the proportion of the multiple micronuleated
cells increased in a concentration-dependent manner in the concentration range of
SNP (0.5-4 micromol/ml with S9 or 2-8 micromol/ml without S9). Our results
indicate that SNP, an NO releasing drug, is genotoxic in g12 cells.
PMID- 9639690
TI - Induction of telomerase activity and chromosome aberrations in human tumour cell
lines following X-irradiation.
AB - Telomerase, a ribonucleoprotein enzyme, has been detected in immortalised cells
and in majority of human cancers. Numerical and structural chromosome aberrations
are commonly observed in tumour cell lines. To study the expression of telomerase
and its influence on the formation of chromosomal aberrations, human colon
carcinoma cell line (SW480) and human nonpolyposis colorectal carcinoma (HNPCC)
cell lines (NA50600, NA59 and NA61) were exposed to 2 or 4 Gy X-rays. Increased
telomerase activity was observed in all these cell lines at 24 h postirradiation
and a 3 to 7 fold increase was seen at 4 Gy dose as detected by Telomere Repeat
Amplification Protocol. Chromosomal rearrangements (dicentrics, translocations
and breaks/fragments) analysed by Giemsa staining and chromosome painting were
increased significantly following X- Quantitative fluorescence in situ
hybridisation using a peptide nucleic acid telomeric probe to measure telomere
length at irradiation chromosomal level revealed that all cell lines have very
short telomeres in the range of 0.29 to 2.1 kb. Following X-irradiation, an
increase in the chromosome end-to-end (telomere) associations was observed. The
present results demonstrate that presence or upregulation of telomerase activity
did not prevent the formation of chromosome aberrations and/or telomere
associations in tumour cell lines after X-irradiation.
PMID- 9639691
TI - In vitro antimutagenic and in vivo anticlastogenic effects of carotenoids and
solvent extracts from fruits and vegetables rich in carotenoids.
AB - The water insoluble residues of some carotenoid-rich fruits and vegetables, such
as apricots, oranges, brussels sprouts, carrots, yellow-red peppers, and
tomatoes, were sequentially extracted with n-hexane, dichloromethane, acetone,
and 2-propanol, and solvent extracted materials were tested for inhibition of
mutagenicities induced by aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), 2-amino-3
methylimidazo[4,5-f]quinoline (IQ), and cyclophosphamide (CP) in histidine
deficient strains of Salmonella typhimurium. Antimutagenic activities were found
in many extracts, but especially in the n-hexane extracts. For example, in the
case of oranges, 100 microg of this extract reduced the bacterial mutagenicity of
AFB1, BaP, CP and IQ by 72, 67, 53, and 27%, respectively. Separation by semi
preparative HPLC of the n-hexane extracts of carrots, tomatoes, and oranges
indicated that the antimutagenicity was mainly associated with the fractions of
the hydrocarbon carotenoids (alpha-, beta-carotene, lycopene), the xanthophylls
(beta-cryptoxanthin, lutein), and also the carotenolesters (oranges). When 16
reference carotenoids were investigated as described above, the following results
were obtained: In the case of BaP, antimutagenic activity, quantified by dose
response curves, was exhibited by 8'-apo-beta-carotenal, alpha- and beta
carotene, beta-cryptoxanthin, lutein, retinal, and retinol (ID50-values: 20-100
nmol ml-1 top agar, 50-70% maximum inhibition at 1 micromol ml-1 top agar), while
the maximum inhibition by torularhodin did not exceed 40%. Astaxanthin, 10'- and
12'-apo-beta-carotenal, bixin, canthaxanthin, ethyl-8'-apo-beta-caro-ten-8'-oate,
lycopene, and zeaxanthin were inactive or at best marginally active (<20%
inhibition). Closely similar results were obtained with AFB1. The bacterial
mutagenicity of CP was strongly reduced by alpha- and beta-carotene,
canthaxanthin, and retinol (ID50-values: 67-112 nmol ml-1 top agar, 50-63%
maximum inhibition at 1 micromol ml-1 top agar), moderately by beta
cryptoxanthin, and lutein (45% and 28%, respectively), and only marginally or,
not at all, by all remaining carotenoids. In the case of IQ, the carotenoids
exhibited the weakest antimutagenic potency (7-43%, ID50-values of retinal and
retinol: 160 and 189 nmol ml-1 top agar, 60% and 55% inhibition, respectively).
The mutagenic activity of the proximal mutagen of IQ, N-OH-IQ, in S. typhimurium
TA 98NR was not significantly reduced by any carotenoid tested. These
observations as well as the inhibition of various cytochrome P-450 linked 7
alkoxyresorufin-O-dealkylase activities (EROD, MROD, PROD) by four selected
carotenoids (retinol>beta-cryptoxanthin>beta-carotene>lutein, IC50-values: 19-109
microM), indicate that the inhibition of the metabolic activation of the
different promutagens could cause antimutagenicity. Finally, it could be
demonstrated that the number of BaP or CP induced micronuclei in polychromatic
erythrocytes in bone-marrow of mice was reduced significantly by the carotenoids
lycopene, canthaxanthin, lutein and beta-cryptoxanthin (25-46%). These results
clearly show that carotenoids possess biological activities in vitro and in vivo
distinct from their function as precursors of vitamin A or antioxidants
suggesting effects on activation of promutagens.
PMID- 9639692
TI - Efficient protection of cells from the genotoxicity of nitrosoureas by the
retrovirus-mediated transfer of human O6-methylguanine-DNA methyltransferase
using bicistronic vectors with human multidrug resistance gene 1.
AB - Retrovirus-mediated transfer of O6-methylguanine-DNA methyltransferase (MGMT;
E.C. 2.1.1.63) and a human multidrug-resistance gene (MDR1) confers resistance to
nitrosoureas and natural product antitumor agents, respectively. In a previous
study, we constructed two bicistronic retroviral vectors, Ha-MDR-IRES-MGMT and Ha
MGMT-IRES-MDR, that allow co-expression of the MGMT gene and the MDR1 gene to
protect cells from the toxicity of combination chemotherapy. Each cell transduced
with Ha-MDR-IRES-MGMT or Ha-MGMT-IRES-MDR showed high-level resistance to
vincristine and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3
nitrosou rea (ACNU), indicating that the two drug-resistance genes can be
functionally co-expressed from these vectors. In the present study, we examined
whether the expression of MGMT from these MDR1-MGMT bicistronic retroviral
vectors could protect cells from the genotoxicity of nitrosoureas. Three
independent Ha-MDR-IRES-MGMT-transduced clones and three independent Ha-MGMT-IRES
MDR-transduced clones of HeLa MR cells showed 12-23-fold and 27-30-fold higher
MGMT activity than the parental cells. These clones are more resistant to ACNU
mutagenicity measured by the frequency of the emergence of 6-thioguanine
resistant colonies after ACNU treatment over the frequency seen in the parental
cells. The ACNU-induced sister chromatid exchange (SCE) was markedly suppressed
in these clones. Murine bone marrow cells were transduced with either Ha-MDR-IRES
MGMT or Ha-MGMT-IRES-MDR. Non-selected populations of the transduced cells showed
only marginal increases in drug resistance and MGMT activity. Remarkable increase
in drug resistance and MGMT activity were observed after a short exposure of the
transduced cells to vincristine. The Ha-MDR-IRES-MGMT-transduced, vincristine
selected bone marrow cells showed 27-fold resistance to vincristine, 7-fold
resistance to ACNU, and 10-fold higher MGMT activity than the non-transduced, non
selected cells. The Ha-MGMT-IRES-MDR-transduced, vincristine-selected cells
showed 8-fold resistance to vincristine, 16-fold resistance to ACNU and 19-fold
higher MGMT activity than the non-transduced, non-selected cells. The rates of
ACNU-induced SCE in the vincristine-selected cells were as follows: non
transduced cells (non-selected) and HaMDR-transduced cells>Ha-MDR-IRES-MGMT
transduced cells>Ha-MGMT-IRES-MDR-transduced cells. Again, the only marginal
levels of increases in the rates of ACNU-induced SCE were observed in non
selected population of the transduced cells. These results indicate that the MDR1
MGMT bicistronic retrovirus vectors would be useful to protect normal
hematopoietic cells from nitrosourea-induced mutagenesis, and drug-selectable
bicistronic constructs would have great advantage over non-selectable vectors.
PMID- 9639693
TI - Induction of somatic DNA damage as measured by single cell gel electrophoresis
and point mutation in leaves of tobacco plants.
AB - The induction and measurement of DNA damage in nuclei of plant tissues is a new
area of study with the alkaline single cell gel electrophoresis/comet assay.
Methods to isolate plant cell nuclei cause high levels of DNA damage which are
detected by the comet assay. We developed a method to isolate nuclei from leaf
tissue of Nicotiana tabacum (a1+/a1; a2+/a2) in a modified Sorensen buffer that
resulted in constant, low tail moment values for the negative controls. After
treating intact tobacco plants with 1-8 mM ethyl methanesulfonate (EMS) we
obtained a direct concentration-response with an average median tail moment of
65.9+/-4.4 micro(m) for plants exposed to the highest EMS concentration as
compared to the median control tail moment value of 4.1+/-0.8. We found that the
highest resolution was obtained with electrophoretic conditions of 0.74 V/cm at
300 mA for 20 min. Multiple leaves could be analyzed per plant within each
treatment group and the tail moments were not significantly different. Tobacco
seedlings were treated with EMS in the same manner as used for the comet assay
and mutations were induced in the leaf primordia. The mean mutant frequency for
the control was 1.46+/-0.20 mutant sectors/leaf. The mutant frequency increased
in a concentration dependent manner; the mutant frequency induced by 8 mM EMS was
37.89+/-2.37 mutant sectors/leaf. The comet tail moment values and the leaf
mutant frequency were highly correlated (r=0.98). The genetic response factor was
calculated by the ratio of the difference in the response within the linear
portion of each concentration-response curve divided by the slope of the curve.
The genetic response factor for the tail moment was 7.82 while the value for
mutation induction was 7.76. In this paper we describe a sensitive method with
high resolution to apply the alkaline comet assay to plant leaves. The comet
assay response was compared to that of induced point mutation. With this
sensitive method for nuclei isolation from plant leaves, the alkaline SCGE assay
could be incorporated into in situ plant environmental monitoring.
PMID- 9639694
TI - Involvement of oxidative stress in motorcycle exhaust particle-induced DNA damage
and inhibition of intercellular communication.
AB - In this study, we investigated the involvement of reactive oxygen species (ROS)
in the motorcycle exhaust particle (MEP)-induced genotoxic and non-genotoxic
activity in mammalian cell systems. Initially, the capability of MEP to induce
ROS was evaluated by using 2',7'-dichlorofluorescin diacetate (DCFH-DA) to detect
hydrogen peroxide (H2O2). A five-fold increase in H2O2 was observed in Chinese
hamster lung V79 and human lung carcinoma Calu-1 cells treated with 100 microg/ml
MEP for 2 h. Under the same experimental conditions, only a two-fold elevation in
H2O2 was detected in hepatic cell systems such as BNL.Cl.2, HepG2, and Hep3B.
Treatment of the V79 cells with varying concentrations of MEP caused a dose
dependent increase in sister chromatid exchanges (SCEs), which are effectively
inhibited by addition of antioxidants, N-acetyl-l-cysteine (NAC) and ascorbic
acid. Furthermore, we determined the oxidized bases in the V79 cells after
exposure to MEP. The result showed that 500 microg/ml MEP induced a 3.7-fold
increase in thymine glycol (TG) and a seven-fold increase in 8-hydroxy-guanosine
(8-OHGua) as compared to untreated cells. We subsequently examined whether MEP
would affect gap junctional intercellular communication (GJIC), a tumor promotion
process, in V79 cells. We found that MEP inhibited GJIC in a dose-response
fashion. Maximal inhibition occurred at 500 microg/ml. The concentration that
inhibited at 0.5 of the fraction of the control was 200 microg/ml. Interestingly,
when cells were pretreated with NAC or ascorbic acid, they could abolish the MEP
mediated inhibition of GJIC. In addition, a moderate decrease of glutathione was
observed in the V79 cells during exposure to MEP. Taken together, our findings
suggest that MEP can induce oxidative stress in a broad range of cell lines,
especially in lung cell systems. The MEP-induced oxidative stress was critically
involved in both genotoxic and non-genotoxic activity.
PMID- 9639695
TI - C-mitotic effects of trichloroethylene (TCE) on bone marrow cells of mice.
AB - The possible aneuploidy inducing activity of Trichloroethylene (TCE, CAS No. 79
01-6) an industrial chemical was investigated by employing three cytogenetic end
points i.e., C-mitotic effects, Micronuclei (MN) and parallel chromosome
structural aberration (CA) analysis in vivo. The experiments were conducted in
mouse bone marrow cells. The animals were treated with TCE in the dose of 500,
1000, 2000 and 4000 mg/kg for 6, 12, 24, 48 hr. Colchicine (COL) was taken as
positive control for its known aneuploidy-inducing effects and Cyclophosphamide
as a model mutagen. TCE showed positive CM effects accompanied with increases of
Mitotic Index and decreased frequencies of anaphases in higher doses. The
chemical showed a positive MN response in bone marrow polychromatic erythrocytes
but was negative in CA analysis. The preliminary results indicated that TCE is
capable of inducing C-mitotic effects in mouse bone marrow cells which is
suggestive of its possible aneuploidy induction potential.
PMID- 9639696
TI - Comparative mutational spectra of the nitrogen mustard chlorambucil and its half
mustard analogue in Chinese hamster AS52 cells.
AB - Nitrogen mustards play an important role in current cancer chemotherapy. The most
effective antitumour agents are those carrying two alkylating functions, probably
through their ability to form interstrand cross-links in DNA. Such lesions appear
to create more of a block in DNA replication and are more difficult to repair
than are most monoadducts. Although there were early reports that monofunctional
drugs were more mutagenic than the bifunctional drugs, this has not been formally
proved using structurally related drugs in a mutagenicity assay capable of
detecting a range of different events. We have studied both the mutagenic potency
and spectrum of events caused by treatment with the clinical agent, chlorambucil,
compared with its half-mustard analogue, in Chinese hamster ovary (CHO)-AS52
cells. Although both drugs caused comparable increases in mutation frequency at
doses killing 90% of cells (from around 9x10-6 to around 9x10-5 mutant cells),
the nature of events differed significantly between the drugs. By far the
majority of mutations caused by the half-mustard were transversion mutations, and
almost all of these could be interpreted in relation to the DNA adducts that are
known to be formed. In contrast, the majority of chlorambucil-induced mutations
were major deletions, and point mutations were only identified from a few clones.
Parallel micronucleus assays verified that chlorambucil has a stronger ability to
break chromosomes than the half-mustard. These two drugs are thought to form
similar monoadducts, but only the full mustard can form interstrand cross-links.
The data suggest that DNA cross-links, although only a minor fraction of the
total lesions, dominate the mutagenic spectrum and lead to gross changes at the
chromosome level that can not be readily associated with individual lesions
produced by the drug.
PMID- 9639697
TI - In vitro investigation of toxaphene genotoxicity in S. typhimurium and Chinese
hamster V79 lung fibroblasts.
AB - The polychlorinated pesticide toxaphene has been identified as a persistent
environmental contaminant and is of particular concern in the Great Lakes and
Arctic regions of Canada. Inconsistencies in published in vitro genotoxicology
studies have hindered risk assessments of toxaphene exposure. When toxaphene
mutagenicity was re-evaluated in the Ames Salmonella/microsome assay at 10-10,000
microg/plate, a dose-dependent increase in His revertants occurred in all five
strains of S. typhimurium tested (TA97, TA98, TA100, TA102 and TA104) with higher
mutation frequencies observed in the absence of S9 metabolic activation. However,
the mutagenic potential of toxaphene was relatively low with concentrations
greater than 500 microg/plate required to induce mutation. Toxaphene genotoxicity
was also examined in a mammalian system using Chinese hamster V79 lung
fibroblasts with metabolic activation provided by human HepG2 hepatoma cells.
Genotoxicity of 1-10 microg/ml toxaphene was examined by measuring the frequency
of sister chromatid exchange (SCE) and mutation induction at the hypoxanthine
guanine phosphoribosyl transferase (HGPRT) gene locus. Although small increases
in SCE were observed at toxic concentrations of toxaphene approaching the LD50
(10 microg/ml), they were not found to be statistically significant relative to
control. Toxaphene was also unable to induce HGPRT mutagenesis at the
concentrations tested. These results show that while toxaphene is a weak, direct
acting mutagen in the Ames Salmonella Test, convincing evidence of dose-dependent
SCE induction and mutagenicity at the HGPRT gene locus could not be demonstrated
in V79 cells.
PMID- 9639699
TI - Increased sister chromatid exchange and chromosomal aberration frequencies in
psychiatric patients receiving psychopharmacological therapy.
AB - Combinations of various psychotropic drugs are often used, sometimes for long
periods, in the treatment of various forms of psychiatric disorders. This paper
evaluates the cytogenetic consequences of daily exposure to polytherapy with
antianxiety, antipsychotic and antimaniacal drugs by determining chromosomal
aberrations (CA) and sister chromatid exchange (SCE) in peripheral blood samples.
The study was performed with a group of 36 psychiatric patients: 18 receiving
long-term treatment with lithium carbonate, combined with benzodiazepines (BD)
and antipsychotic agents (Group A) and 18 treated with BD and antipsychotics
(Group B). Among the latter, 7 patients had only been treated for 1 month (Group
B1). The results reveal a significant increase (p<0.01) in cells with aberrations
in the two groups of patients (A,B) compared to controls. Moreover, complex
aberrations (dicentrics, rearrangements, chromatid exchanges) had a frequency of
0.63% in patients receiving long-term treatment compared to 0.11% in controls,
corresponding to the general spontaneous rate. The mean frequency of SCE/cell and
the percentage of cells with a high frequency of exchanges (HFC) also showed a
highly significant difference compared to controls in both Group A and Group B.
Group B1 (patients who only commenced treatment 1 month earlier) did not differ
from the control group with regard to the frequency and type of chromosomal
aberration or in relation to the mean frequency of SCE/cell. No significant
differences were detected between Groups A and B both of which showed similar
frequencies of cells with aberrations, SCE/cell and HFC. No correlations were
observed in Group A between lithemia and the biological markers studied.
PMID- 9639698
TI - Comparison of in vivo mutagenesis in the endogenous Hprt gene and the lacI
transgene of Big Blue(R) rats treated with 7, 12-dimethylbenz[a]anthracene.
AB - The lacI transgene of Big Blue(R) (BB) rats was evaluated as a reporter of in
vivo mutation by comparing mutant frequencies (MFs) in it and in the endogenous
Hprt gene. Seven-week old female BB rats were given single doses of 0, 20, 75 and
130 mg/kg of 7, 12-dimethylbenz(a)anthracene (DMBA) by gavage, and Hprt and lacI
MFs in splenic lymphocytes were measured over a period of 18 weeks. The Hprt MFs
in treated rats increased for 10 weeks and then declined; 130 mg/kg of DMBA
produced a maximum Hprt MF of 168+/-11.4x10-6 clonable lymphocytes, while the MF
in control rats was 7.4+/-1. 5x10-6. DMBA exposure of generic F344 rats resulted
in a similar time-course of mutant induction but produced about 50% higher Hprt
MFs with the 75 and 130 mg/kg doses. In contrast, the lacI MFs increased for 6
weeks and then remained relatively constant; 130 mg/kg of DMBA produced a maximum
increase in lacI MF of 341+/-83x10-6 PFU compared with 25+/-5x10-6 PFU in control
rats. The Hprt mutant frequencies in DMBA-treated BB and F344 rats were
significantly increased over control values for every dose-time combination
examined, while only the 130 mg/kg dose consistently produced lacI MFs that were
significantly above the controls. In addition, the fold-increase in MF for
treated vs. control rats was two times higher for the Hprt gene than the lacI
gene due to the higher MFs in the lacI gene of control rats. Differences between
the lacI and Hprt genes in the kinetics of mutant induction, in the frequency of
induced mutants, and in the sensitivity of mutant detection could be explained at
least partially by the properties of these two genes.
PMID- 9639700
TI - Mutagenic interactions between X-rays and two promutagens, o-phenylenediamine and
N-nitrosodimethylamine, in the stamen hairs of Tradescantia clone BNL 4430.
AB - Mutagenic interactions between X-rays and two promutagens, o-phenylenediamine
(PDA) and N-nitrosodimethylamine (DMN), were studied in the stamen hairs of
Tradescantia clone BNL 4430, a blue/pink heterozygote. The young inflorescence
bearing shoots with roots of this clone cultivated in a nutrient solution
circulating growth chamber were used as tester plants. After determining dose
response curves for X-rays. PDA and DMN, combined treatments with PDA or DMN and
X-rays were conducted, exposing acutely to X-rays 20 h before starting, at the
midpoint of, or 20 h after completing the PDA or DMN treatments for 4 h. Clear
synergistic effects in inducing somatic pink mutations were detected when X-rays
were irradiated before the PDA or DMN treatments, resembling those confirmed
earlier between maleic hydrazide (MH) and X-rays. On the contrary, clear
antagonistic effects were observed when X-rays were given after the PDA or DMN
treatments, also resembling those between MH and X-rays. When X-rayed at the
midpoint of the PDA or DMN treatments, merely additive and synergistic effects
were observed, respectively, differing from the antagonistic effects between MH
and X-rays. The mutagenic synergisms detected were considered to be the results
of interactions between DNA strand breaks (and the resultant chromosome breaks)
induced by X-rays and those by PDA or DMN, whereas the mutagenic antagonisms
observed were presumed to be due to X-ray-caused inhibition of the activation of
PDA and DMN in the stamen-hair cells. The time periods required for penetrations
into floral tissues and/or activations into mutagens seem different among PDA,
DMN and MH.
PMID- 9639701
TI - High and low UV-dose responses in SOS-induction of the precise excision of
transposons tn1, Tn5 and Tn10 in Escherichia coli.
AB - UV-inducible precise excision of transposons is a specific SOS-mutagenesis
process. It deals with the deletion formation which has previously been
demonstrated to involve direct or inverted IS-sequences of transposons. The
process was used for revisiting the targeted and untargeted SOS-mutability and
its relationship to the key genes for SOS-mutagenesis: the recA, lexA and umuDC.
The precise excision of transposons Tn5 and Tn10 from the chromosomal insertion
sites ade128 and cyc750 is induced in Escherichia coli K-12 and B cells, wild
type for DNA-repair, both by the low doses of UV-light ranging from 0.25 J m-2 to
2.5 J m-2 and the high doses within the range 5.0-40.0 J m-2. Precise excision of
these transposons induced by the range of low doses incapable to induce targeted
point mutations reveals its mostly untargeted nature. This process for the
transposon Tn1 is not induced by UV-light within the range of doses 0.25-2.5 J m
2 while its induction is possible by UV-fluences ranging from 5.0 to 40.0 J m-2.
A dose-response of the precise excision of Tn1 is similar to that of the UV
induced reversion of trpUAA point mutation that is targeted by nature and
contrasts to the UV-inducible precise excision of Tn5 and Tn10. Both types of UV
inducible precise excision, demonstrated either by Tn1 or Tn5 and Tn10, are
eliminated by mutations in the lexA, recA and umuDC genes indispensable for UV
induced SOS-mutability. The palindromic structures different for the transposons
Tn1, Tn5 and Tn10 are discussed to be involved and affect the targeted and
untargeted precise excision of transposons induced by UV-light.
PMID- 9639702
TI - Induction of micronuclei in the domestic cat (Felis domesticus) peripheral blood
by colchicine and cytosine-arabinoside.
AB - One advantage of bioassays over other kinds of tests is the processing or
metabolism of the compound by the organism. In a previous work, in which we
reported the number of micronucleated erythrocytes (MNE) in the peripheral blood
of 35 species, the cat was one of the species with the highest number of
micronuclei (MN). Cats have a low level of circulating polychromatic erythrocytes
(PCE), i.e. 0.05%, which is much lower than in the laboratory mouse, but higher
than in species such as cows, donkeys, sheep, goats and horses. Thus, MN were
scored in total blood erythrocytes. In the present work, we assess the cat as a
test system for MN induction. Three doses of a colchicine-cytosine arabinoside
mixture were administered to young cats during 4 days; then, the numbers of MNE
in blood collected before the first injection and 48 and 96 h later were
compared. The number of MNE increased with time, reaching the highest values in
the samples taken 96 h after the administration of the micronucleogenic agents.
PMID- 9639703
TI - Genotoxic activity of four inhibitors of DNA topoisomerases in larval cells of
Drosophila melanogaster as measured in the wing spot assay.
AB - Four inhibitors of DNA topoisomerases namely nalidixic acid, camptothecin, m
amsacrine and etoposide, have been evaluated for genotoxic effects in the wing
spot test of Drosophila melanogaster. This assay assesses somatic recombination
and mutational events. We studied nalidixic acid as an inhibitor of bacterial DNA
gyrase, camptothecin as a topoisomerase I inhibitor, as well as m-amsacrine and
etoposide as topoisomerse II inhibitors. The genotoxic effects were determined
from the appearance of wing spots in flies trans-heterozygous for the recessive
markers multiple wing hairs (mwh) and flare, as well as in flies heterozygous for
mwh and the multiply inverted TM3 balancer chromosome. From our results it
appears that whilst nalidixic acid and m-amsacrine were compounds that did not
increase the incidence of mutant clones, camptothecin and etoposide proved to be
significantly genotoxic in this test, being camptothecin more effective than
etoposide. A significant proportion of the total spot induction was due to
mitotic recombination, confirming previously reported data. On the other hand,
the cotreatments of each topoisomerase inhibitor with the alkylating agent ethyl
methanesulfonate (EMS) indicate that, while nalidixic acid, m-amsacrine and
etoposide show a tendency to an antagonistic interaction, camptothecin shows an
additive effect, suggesting mechanistic differences between the activity of the
four inhibitors of DNA topoisomerases studied.
PMID- 9639704
TI - Cytogenetic study on children living in Southern Urals contaminated areas
(nuclear incidents 1948-1967).
AB - As a result of the activities of the first Soviet plutonium production reactor,
large territories of the Southern Urals were exposed to radioactive
contamination. Three different incidents occurring between 1948 and 1967 lead to
major exposure. A total of 280,000 people residing on the contaminated
territories were exposed both to external and internal contamination particularly
due to the long-lived radionuclides 137Cs and 90Sr. The highest doses were
received by 28,000 people living on the Techa riverside villages. In the present
paper 15 presumably exposed children coming from the Muslyumovo village on the
Techa river have been analyzed using conventional cytogenetic procedure in order
to assess a radiation-induced damage. The data obtained have been compared to a
group of matched unexposed controls. The results show a statistical difference
between the two cohorts which suggests a possible residual contamination
representing a continuous hazard for the new generations.
PMID- 9639705
TI - Characterization of gamma irradiation-induced deletion mutations at a selectable
locus in Arabidopsis.
AB - Seeds of transgenic Arabidopsis, containing a negatively selectable suicide
marker, a 35Stms2 construct introduced as a transgene, were gamma-irradiated at a
range of doses from 20-120 krad. Batches of M2 seeds, from M1 plants irradiated
at doses of 40, 45 and 60 krad, were screened by germinating them on medium
containing NAM under conditions that selectively inhibited growth of plants
expressing the tms2 gene product. Nine candidate loss-of-transgene mutants were
isolated. The frequency of such mutations (0.0125 to 0.025%) did not vary
significantly with irradiation dose or M1 pool size. DNA from the mutants and the
parent was hybridized in Southern blots, using probes complementary to various
regions of the transgene. All nine mutants were null for both the tms2 coding
sequence and the 35S promoter. Six of the nine mutants were null for the entire
transgene construct of 9 kbp. DNA from one mutant contained one of the T-DNA
borders and gave a hybridization pattern consistent with a deletion at least 5
kbp. The two remaining mutant lines gave identical patterns of hybridization,
consistent with a 5.6-kbp internal deletion within the transgene. From the
Southern blots, and on the basis of lineage, the nine lines represent the progeny
of either seven or eight independent mutations. We have established conditions
capable of producing deletion mutations of at least 5 kbp, but without apparently
introducing small deletions or rearrangements. Such deletion mutations are
ideally suited for cloning by subtractive hybridization, and should also be
readily detectable by RFLP analysis, facilitating map-based cloning procedures.
PMID- 9639706
TI - [Development of tertiary disciplines in otorhinolaryngology].
PMID- 9639707
TI - [The cochlea in short-term culture].
AB - In order to establish organotypic culture of the cochlea, the dissection of the
early postnatal mouse cochlea and its morphology in short-term culture were
investigated. The viability of hair cells in the culture was assessed using
differential interference contrast (DIC) microscopy and double-staining with
fluorescein diacetate (FDA) and propidium iodide (PI). The hair cells remained
viable and did not show any signs of damage for up to 8-18 hours. When incubated
in Hank's solution containing 1 mmol/L dihydrostreptomycin, the hair cells
initially deteriorated in 0.5-4.5 hours and progressed to entire degeneration
after 10-20 hours. In addition to its utilization in organotypic culture, the
cochlea in short-term culture can be used as a valuable model for studying
cellular and molecular neurobiology of the inner ears.
PMID- 9639708
TI - [Effect of epidermal growth factor and dexamethasone on blast hearing loss].
AB - The expression of epidermal growth factor receptor (EGFR) in cochlear hear cells
was studied in normal and guinea pigs exposed to blasts. The effects of epidermal
growth factor (EGF) and dexamethasone (DXM) treatment for blast hearing loss and
the underlying mechanisms were also explored. Scattered expression of EGFR was
seen in IHCs and OHCs in normal guinea pigs. Segmentally distributing positive
reaction was also located in stereocillia of hair cells. Distribution of EGFR
reaction was seen in the cytoplasm of IHC 24 hours after exposure to blasts, and
in the stereocillia of IHC and the cuticular plate of OHC 72 hours postexposure.
At one week EGFR reaction in hair cells increased obviously and part of OHC
stereocillia also showed positive reaction. EGFR reaction reduced at two weeks,
though positive reaction could still be found in the stereocillia of hair cells
at one month. Combination of EGF and DXM administrations promoted hearing
recovery significantly. Our results suggest that healing of injured hair cells
may be to EGF.
PMID- 9639709
TI - [Computer image analysis in the study of endolymphatic hydrops].
AB - In search for an objective method to be used to judge the extent of hydrops,
computer image analysis system was used in the study on guinea pig endolymphatic
hydrops. The image information of the whole cochlea was collected, then the
length of Reissener's membrane and section area of scala media were calculated
based upon parameters such as ratio factors and point values. The results were as
follows: 1) Hydrops observed with light microscope had no statistical difference.
2) Within 55 days postoperatively, the hydrops grew more obvious with time. 3)
The hydrops was more extensive in the basal turn than in the apical turn, though
more conspicuous cytopathologic change was found in the apical turn. The
conclusions: 1) The current technique is objective, accurate and reliable. 2)
Both the length of Reissener's membrane and section area of scala media can be
used to measure the extent of hydrops.
PMID- 9639710
TI - [Dynamic effects of sulphuric gentamicin on vestibular function in guinea pigs].
AB - Sinusoidal rotation and rotational stimulation tests were used to examine
vestibular function in guinea pigs. The results showed that there was no
statistically significant difference in the mean number of nystagmus of semi
cycle sinusoidal rotation test and the duration of nystagmus of rotational
stimulation test for both the control and test groups before treatment in albinos
and pigmented guinea pigs. Meantime, daily subcutaneous injection of gentamicin
125 mg/kg body weight for 12 days in albinos and pigmented guinea pigs showed no
significant change in vestibular function until the 7th day of treatment.
Significant impairment of vestibular function was noticed on the 10th treatment
day. At 5 days after treatment vestibular impairment reached its maximum and
minimal recovery was seen at 14 days after treatment. No Further improvement of
vestibular function was noticed three months after treatment. The methods are
feasible and reliable.
PMID- 9639711
TI - [Failure in mastoidectomy with posterior canal wall preservation and
tympanoplasty case analysis].
AB - Preservation of the posterior canal wall in mastoidectomy is essential for
rebuilding normal tympanum and conductive structures, and has been widely
recommended. However, controversies remain about the technique due to its
complications and diverse results reported. This paper analysed the causes of
four failed cases in detail and proposed measure to reduce morbidities and
promote success. The review includes case selection, operation staging, surgical
techniques and lesion removal etc.
PMID- 9639712
TI - [Vestibular and auditory functions in Meniere's disease].
AB - This paper is, aiming at understanding disturbances of and correllation between
colchear and vestibular functions in Meniere's disease. Auditory and vestibular
functions in 121 Meniere cases (70 males and 51 females, age ranging from 19 to
63 years), diagnosed according to the AAO-HNS criteria, were analysed. The
results were as follows: 1)There was positive correlation between semicircular
canal paresis and hearing impairment. 2) There was statistically significant
positive correlation between hearing impairment and the -SP/AP ratio. 3) There
was statistically significant correlation between hearing impairment and glycerin
test result, the rate of positive result being higher in those with advanced
hearing loss than in those with mild loss. 4) There was correlation between the
rate of positive glycerin test result and audiogram configuration. The rate with
rising audiogram pattern was higher than with that falling pattern (69.0% vs
33.3%). It was also found that ECochG was far more effective than glycerin test
in diagnosing Meniere's disease. The physiologic basis and significance of ECochG
and glycerin test in Meniere's disease were discussed.
PMID- 9639713
TI - [Endoscopic surgery of the cerebellopontine angle].
AB - Twenty-four patients with various cerebellopontine angle (CPA) disorders
including hemifacial spasm (11 cases), trigeminal neuralgia (9 cases),
glossopharyngeal neuralgia (2 cases) incapacitating vertigo and acoustic neuroma
(one case each), were treated by endoscopic surgery, via the retrosigmoid
approach. Because of the distal light and panoramic view, the endoscope provides
an excellent view inside the CPA, allows clear identification of the vascular and
nervous components, and is especially helpful in cases of trigeminal neuralgia
and hemifacial spasm to find the location of cross-conflict. Under the monitor of
endoscope, the surgeon is able to perform facial nerve decompression and
splitting, selective trigeminal nerve root and glossopharyngeal nerve section
with ease and safty. The present study shows that the endoscopic surgery is a
simple and useful procedure which helps to reduce surgical complications. We
recommend the application of endoscopy in the management of CPA disorders.
PMID- 9639714
TI - [Anatomy of the endolymphatic sac and its clinical significance].
AB - Using 28 formalin fixed temporal bones and materials of 26 cases of endolymphatic
surgery for menieres' disease, the location, vascular distribution and size of
the endolyphatic sac (ELS) were investigated. ELS were measured with surgical
microscope in all the cadaver specimen with a mean length of 6.9393 +/- 2.0429 mm
and mean width of 5.8821 +/-1.6522 mm. All the specimens showed no clear
capillary distribution. Only in 24 of the 26 ELS surgeries for Menieres' disease
the ELS were found. The mean length was 6.8125 +/- 2.2449 mm, the mean width
5.6666 +/- 1.5084 mm and the vascular distribution was unclear in 29% of the
cases. It was found that the ELS usually located at the Donaldson line, and moved
downward in the under-developed mastoid with smaller size.
PMID- 9639715
TI - [Cluster epithelial cells in nasal secretions of allergic rhinitis and its
relation to eosinophils].
AB - The cytology of nasal secretions in 20 patients with allergic rhinitis and 15
patients with chronic maxillary sinusitis was investigated with transmission
electron microscope to study the ultrastructure of the cluster epithelial cells
in nasal secretions of allergic rhinitis. The results showed that the cluster
epithelial cells were predominant cellular element in allergic nasal secretions.
The number of cluster cells correlated positively with the number of eosinophils
and the levels of eosinophilic cationic protein. It is suggested that the
exfoliation of cluster nasal epithelial cellular elements may be caused by
eosinophic cationic protein with resultant hyperreactivity of nasal mucosa.
PMID- 9639716
TI - [Estradiol receptors expression in nasal polyps and its significance].
AB - Nasal polyps are generally considered as a result of extreme nasal mucosal edema
induced by long-term recurrent inflammation of the respiratory mucosa. The
estradiol (E2) has been demonstrated to play a facilitating role in nasal
inflammation. To evaluate the effect of estradiol on the pathogenesis of nasal
polyps, the expression of E2 receptors in paraffin section from patients with
nasal polyps (84 cases), chronic hypertrophic rhinitis (6 cases) and healthy
control subjects were investigated by means of immunohistochemistry for E2
receptors and toluidine blue staining for mast cells. It was shown that there was
high expression of E2 receptors in 61 out of 84 cases (male 40, female 44) of
nasal polyps and the expression distributed equally among both sexes. Low
expression of E2 receptors presents in 2 out of 6 cases of chronic rhinitis and 1
out of 4 healthy subjects. Noteworthily, the E2 receptor expressing cells are
similar with the mast cells in shape and distribution. The authors speculate that
they may be identical cells. E2 receptor expression in nasal polyps suggests that
estradiol plays certain role in the development of nasal polyps.
PMID- 9639717
TI - [Metastatic potential correlates with cell surface carbohydrate profiles of
nasopharyngeal carcinoma].
AB - In order to investigate the changes in glycoprotein structure between non
metastatic and metastatic cells of nasopharyngerl carcinoma (NPC), peanut
agglutinin (PNA), ulex europeaus (UEA-I) and concanavalin ensifomis agglutinin
(ConA) staining were used to examine 102 nasopharyngeal carcinoma tissues (84
primary tumors and 18 metastatic lymph nodes) with the avidin-biotinperoxidase
complex method. PNA reaction was positive in most cells of nasopharyngeal
carcinomas regardles of in histopathologic type, the degree of differentiation
and metastasis. The levels of UEA-I receptors apparently increased during
nasopharyngeal carcinoma progression from non-metastatic to metastatic tumors.
The binding to ConA clearly decreased in the cells of metastatic cases and
metastatic lymph node. So, the increased expression of UEA-I receptors and
decrease of ConA receptors on tumor cells might have been implicated in the
expression of metastatic potential.
PMID- 9639718
TI - [Influence of HPD on immunological functions in patients with nasopharyngeal
carcinoma treated by radiotherapy].
AB - Seventy-eight patients with nasopharyngeal carcinoma were equally divided into
two groups: 39 patients were treated by HPD plus radiation and 39 patients by
radiation alone. Immunological functions were evaluated in each patient before
and after radiation. The results showed that (1) in patients treated by RPD and
radiation, no statistical difference was observed on immunological functions
before and after treatment; (2) in patients treatd by radiation alone, the
immunological functions, including OKT3, OKT4, OKT4/OKT8 ratio and lymphocyte
transformation, were significantly decreased after treatment. These findings
indicate that the immunological functions in patients with nasopharyngeal
carcinoma could be protected by HPD during radiotherapy.
PMID- 9639719
TI - [Induction of apoptosis by expression of retroviral mediated wild type p53 gene
in laryngocarcinoma cell line].
AB - The p53 gene is one of the most common targets for genetic abnormalities in human
laryngocarcinoma. In this report, the ability of wild-type p53 gene to induce
apoptosis of laryngocarcinoma cell was examined. The wt-p53 gene recombinant
retroviral vector was constructed and the PA317 packaging cell line producing
virus established. The recipient cell lines of Hep2 (laryngocarcinoma) containing
the abnormal p53 gene were transfected in vitro with 1 ml fresh retroviral stock
produced by the PA317. Southern-blot and Northern-blot were performed using the
probe (1.7 Kb p53 cDNA). Assays for in vitro growth characteristics were
performed. The result showed that introduction of wt-p53 greatly suppressed in
vitro cellular growth of the laryngocarcinoma cell line and identified that the
wt-p53 gene mediated the process of cell apoptosis. In conclusion, the retroviral
vector-mediated wt-p53 gene transfer appeared to be able to induce the apoptosis
in human laryngocarcinoma bearing multiple genetic lesions. The observation
strongly suggests that inactivation of the p53 gene plays a significant role in
the pathogenesis of laryngocarcinoma.
PMID- 9639720
TI - [Epidermal growth factor receptor expression in laryngeal cancer].
AB - The expression of epidermal growth factor receptor (EGFR) in 60 laryngeal
carcinoma and 20 normal laryngeal mucosa was studied with immunohistochemical
LSAB (labelled streptavidin biotin) method to elucidate its role in tumor
progression. EGFR was negative in all 20 normal laryngeal mucosa specimens, and
it was positive in 44 of 60 laryngeal carcinoma specimens. The expression of EGFR
did not correlate with tumor location, tumor stage and lymph node metastasis, but
correlated significantly with histological grading and the survival rate. A
significantly higher positive rate was found in poorly differentiated than in
moderately well differentiated tumors. The 3-year survival rate in patients with
expression of EGFR was much lower than those with negative results (P < 0.01).
The results suggest that EGFR may play an important role in the process of
carcinogenesis in laryngeal mucosa and be used as a useful marker for the
assessment of biological behavior and prognosis of laryngeal carcinoma.
PMID- 9639721
TI - [Bi-pedical and bi-muscle flap reconstruction of the laryngeal function].
AB - The method of reconstruction of laryngeal function by bi-pedical and bi-muscle
flap (DP-DMF) was presented. The DP-DMF was obtained from sternohyoid muscle,
sternothyroid muscle and thyrohyoid muscle. It had enough length, width and
plasticity, applicable to all patients with T3 and T4 laryngeal carcinoma. Up to
now, 102 patients were treated by expanded horizontal hemilaryngectomy and
repaired with unilateral or bilateral DP-DMF. After operation, the swallow
function returned to normal in 7 to 11 days. The tracheal tube extraction rate
was 66.7% (72/108). The 5-year survival rate was 76.5% (62/81), and recurrence
rate was 13.9% (15/108). With the application of DP-DMF, the patients who might
have been treated formerly by total laryngectomy could be treated by partial
laryngectomy. This method expanded the indication of partial laryngectomy,
improved the life quality and survival rate.
PMID- 9639722
TI - [A study on activity of beta-glucuronidase in serum and secretion from upper
respiratory tract in patients with head and neck malignant tumors].
AB - Beta-glucuronidase (beta-GD) activity in serum and upper respiratory tract (URT)
secretion in patients with head and neck malignant tumors (HNMT) was studied.
Subjects included 40 HNMT patients, 40 healthy volunteers and 40 patients with
benign tumors of the head and neck region. The results showed that there was no
statistically significant difference of serum beta-GD level among the three
groups. The same was true for URT secretion between the normal control and benign
tumor groups. beta-GD level in URT secretion was higher in HNMT group than in
other groups (P < 0.001). Using healthy subjects' average beta-GD level plus two
standard difference as positive standard, the sensitivity, reliability and
specificity of the test were 85.0%, 92.5% and 100% respectively. beta-GD levels
were higher in patients with advanced tumors and metastases. One year follow-ups
of six patients showed that beta-GD level change in URT secretion was in
accordance with clinical manifestations. These results suggest that assay of beta
GD level in URT secretion can be used as a valuable supplimental parameter in
early diagnosis of HNMTs, their clinical staging, evaluation of therapeutic
effectiveness and detection of recurrence and metastases. In addition, this
method has the advantage of easy, prompt, result specificity, sensitivity and
reliability.
PMID- 9639723
TI - [Vaginal template implant for cervical carcinoma with vaginal stenosis].
AB - OBJECTIVE: For cervical carcinoma patients with poor geometry for conventional
intracavitary radiotherapy, a simple vaginal template for interstitial
implantation as a substitute was used. This is a report of the treatment results.
METHODS: Patients with vaginal stenosis were treated over from July 1987 to June
1991 with this vaginal template implant as part of the treatment. The applicator
consisted of a front piece and an end piece. Holes were drilled in the front
piece to guide the implantation of the cervix or vaginal vault. The diameter of
applicators varied from 2.0 cm to 3.5 cm. Depending on the diameter of the
applicators, six to eight needles on the periphery, or eight peripheral plus one
central needle were used. The activity of the needles were around 8 mCi with a
total length of 5.5 cm. The end piece was locked onto the front piece by a
bayonet-type locking device. The purpose of the end piece was two-fold: to make
up the length of the whole applicator to fit the vagina and to keep the implanted
needles in place without being extruded. The implantation was performed under
general anesthesia. RESULTS: One of the twelve patients treated with the vaginal
template implant for vaginal stenosis had relapsed centrally but subsequently
died of intercurrent disease. Two other patients died of intercurrent disease at
26.2 and 41.9 months, respectively, without evidence of relapse. Nine other
patients had been followed with no evidence of local relapse for 23.7 to 54.6
months. CONCLUSION: This vaginal template implantation is satisfactory in
treating cervical carcinoma patients with vaginal stenosis.
PMID- 9639724
TI - [loop electrosurgical excision procedure: a review of our recent experience].
AB - OBJECTIVE: To investigated whether persistence or recurrence of cervical
intraepithelial neoplasis (CIN) is associated with an involved excisional margin
during loop electrosurgical excision procedure (LEEP). METHODS: The records of
256 consecutive LEEP were studied. After LEEP, all patients were followed up by
colposcopy and cytology at 4 to 6 month intervals for at least two years. A
patient was classified as having persistent disease if SIL was seen within one
year of treatment or recurrent disease if SIL was detected after one year of
treatment. All relevant patient details including cytology, colposcopy findings,
treatment histology, complications, recurrence or persistence of disease entered
into a computer database. RESULTS: Complications occurred in 8 patients (3.1%).
LEEP was successful in treating 226 patients (95.4)%. Eleven patients (4.6%) had
persistent SIL. Involvement of the resection margin was a significant risk factor
for persistent disease (3.1% for uninvolved margins vs 11.4% for involved
margins, P < 0.05). Similarly, recurrent disease occurred in 9.1% of patients
with involved resection margins vs 2.1% with uninvolved margins (P < 0.05).
Eleven patients (4.3%) had microinvasive carcinoma. Only 3 were identified by
colposcopy and directed biopsy. CONCLUSION: LEEP is established as a safe and
efficacious method for the treatment of CIN, long term morbidity including the
effect on subsequent fertility must be observed.
PMID- 9639725
TI - [Detection of human papillomavirus DNA in cervical squamous cell carcinoma in
Xinjiang Uygur women].
AB - OBJECTIVE: To study the association of cervical cancer with human papillomaviral
(HPV) infection in Uygur women at high risk for development of cervical cancer in
Xinjiang. METHODS: Cervical samples from 65 Uygur women with cervical cancer were
collected. HPV DNA types 6/11, 16/18, 31/33/35 were studied by in-situ
hybridization, and both consensus and type-specific primers for HPV types 6, 16
and 18 were used in 58 cases by polymerase chain reaction (PCR). RESULTS: HPV DNA
was detected in 43.1%, 22.4% and 77.6% of specimens by the in-situ hybridization,
PCR using L1 consensus primers and E6 type-specific primers, respectively.
CONCLUSIONS: E6 type-specific PCR was more sensitive than L1 consesus PCR and in
situ hybridization detection of HPV DNA. These data supported the role of HPV DNA
(particularly HPV 16) in the pathogenesis of cervical carcinoma in high risk
women living in Xinjiang.
PMID- 9639726
TI - [Analysis of the causes of neonatal deaths at term in pregnancy induced
hypertension patients].
AB - OBJECTIVE: To study the neonatal developmental status, its causes of death and
their possible correlation in women complicated with pregnancy induced
hypertension (PIH). METHODS: 46 autopsies of neonatal death at term with PIH and
their clinical data were collected. The developmental status was evaluated by
body weight, body length, and the weights of lungs, kidneys, liver and brain. The
causes of death were reviewed by the clinicopathologic findings. RESULTS: The
neonatal development features for mild PIH in term pregnancy approached to the
normal levels of 37 to 38 gestation weeks. In the infants with moderate and
severe PIH, the body weights, the weights of lungs and liver were significantly
decreased in comparison with those of the mild PIH, respectively (P < 0.05),
while the weights of kidneys and brain were not significantly decreased. The
causes of death showed that pulmonary hypoplasia accounted for 23.9%, primary
pulmonary atelectasis 10.9%, pulmonary hyaline membrane disease 21.7%, massive
pulmonary hemorrhage 13.0%, the meconium aspiration 19.6% and others 10.9%. There
was no difference in sex among the dead infants. CONCLUSIONS: The PIH syndrome
had retarded the process of fetal growth and development, and associated with the
severity of PIH, mostly involving the lung and the liver. The pulmonary
hypoplasia and immaturity were the primary causes for neonatal death in PIH
women.
PMID- 9639727
TI - [Detecting pathogens of fetal defects in paraffin embedded tissues by polymerase
chain reaction].
AB - OBJECTIVE: To examine 3 types of pathogens in dead fetus with congenital defects
for exploring the pathogenesis. METHODS: The paraffin embeded brain and liver
tissues from 39 fetal autopsies with congenital defects were examined for
toxoplasma, cytomegalovirus, and herpes simplex II by polymerase chain reaction.
Among them 16 placentae were examined as well. RESULTS: Pathogens were detected
in 25 of 39 cases, a positive rate of 64%. Nine out of the 13 fetuses with
urogenital defects were positive for the shove pathogens, while 8 from the 12
with neural tube defects were positive as well. CONCLUSION: Intrauterine
infection was one of the important causes of birth defects. The characteristics
of placenta morphologic changes were described, and the significance of placenta
investigation in congenital malformation was emphasized.
PMID- 9639728
TI - [The mechanisms of progesterone treatment on endometrial carcinoma].
AB - OBJECTIVE: To study the mechanisms of the exogenic progestrerone treatment on
endometrial carcinoma. METHODS: We observed the morphologic changes of the
endometrial cancer cells treated by exogenic progesterone with light and
electronic microscopy. RESULTS: The main changes of the tumor cell treated were
well differentiation, increase in secretory activity and apoptosis of tumor
cells. CONCLUSIONS: Progesterone may directly affect tumor cells, inhibit the
growth of tumor cells and lead to well differentiation. Clinically with
preoperative and postoperative progesterone therapy, it can decrease the
peritoneum implantation and metastasis, and also decrease the recurrence after
operation.
PMID- 9639729
TI - [Estrogen and progesterone receptors in endometrial carcinoma].
AB - OBJECTIVE: To study the relationship between estrogen receptor (ER) and
progesterone receptor (PR) and the clinico-pathologic features in endometrial
carcinoma. METHODS: ER and PR contents of fresh tumor tissues taken from 70 cases
of primary endometrial carcinoma were measured by biochemical (DCC) method and 30
paraffin-embedded archival specimens of the 70 cases also by immunohistochemical
(IHC) method. RESULTS: Both ER and PR positive rates were 77.1% by DCC assay and
83.3% by IHC method. Excellent correspondency of one method to the other was
observed (ER 83.3%, PR 86.7%). And the IHC method displayed further the origin of
the tissue examined. The ER and PR levels correlated negatively with the grades
of tumor (P < 0.01). ER and PR positive rates in adenocarcinoma (including
papillary adenocarcinoma) and adenoacanthoma were higher than those in the other
histological types (ER, P < 0.01; PR, P < 0.005). There was a positive
correlation between the ER levels and obesity. CONCLUSIONS: The levels of ER and
PR and the histopathological classification and grading of the tumor tissue
reflect biologic behaviors of endometrial carcinoma. ER and PR assays are
important for endocrinotherapy and in predicting prognosis.
PMID- 9639730
TI - [The effect of gestational impaired glucose tolerance on fetus and newborns].
AB - OBJECTIVE: To study the effect of gestational impaired glucose tolerance (GIGT)
on fetus and newborns. METHODS: 52 GIGT mothers and 34 gestational diabetes
mothers (GDM) were subjected to systematic monitoring prospectively, other 44
normal mothers served as controls. The perinatal outcomes were compared in the
three groups. RESULTS: The incidence of macrosmia in the GIGT group was higher
than that of the control group (P < 0.025). Neonatal blood glucose level in the
GIGT group at 2 hours of age was the lowest in the three groups (P < 0.05). The
incidence of hypoglycemia, polycythemia and wet lung in the GIGT group was higher
than that of the control group. CONCLUSION: GIGT and GDM are important factors
for poor perinatal outcome. Obstetricians and pediatricians must pay more
attention to it.
PMID- 9639731
TI - [Prenatal diagnosis of fetal nuchal cystic hygroma in 22 cases].
AB - OBJECTIVE: To investigate the early diagnosis and prognosis of fetal nuchal
cystic hygroma. METHODS: 72 cases of fetal nuchal cystic hygroma diagnosed in
uterus were analyzed retrospectively. RESULTS: Most of the cases were diagnosed
by B ultrasound between 15-26 gestational weeks. 55.9% the multipara had abnormal
pregnant history, and 40% (4/10) of fetuses with karyotype performed had chrosome
abnormality. Except for fetal deaths and induced abortions, 3 cases had term
deliveries: one neonatal death, one was born with hygroma of 5.9 cm x 3.7 cm and
transferred for surgery, and the other one with hygroma disappeared at the 37th
week and baby was born at 40 week with normal appearance. CONCLUSIONS: This
disease is one of common fetal morphological abnormalities. Few may recover
spontaneously but most have poor outcomes.
PMID- 9639732
TI - [Renin-angiotensin system: involvement in polycystic ovarian syndrome].
AB - OBJECTIVE: To investigate the relationship between renin-angiotensin system (RAS)
and polycystic ovarian syndrome (PCOS) METHODS: A pituitary-stimulating test with
luteinizing hormone releasing hormone (LRH, 100 micrograms) was performed in two
PCOS groups with similar mean testosteron (T) levels of luteinizing
hormone/follicular stimulating hormone (LH/FSH) (LH/FSH > or = 3, group 1, n =
15; LH/FSH < 3, group 2, n = 15) and the controls (n = 20) of matched body mass
index with group 1. The basal level and LRH-evoked responses of LH, plasma renin
activity (PRA), angiotensin II (AT II ) and aldosterone (ALD) were measured by
RIA with commercially available kits. In the basal state, a positive correlation
was found between T and AT II levels (r = 0. 49, P < 0.05) in all PCOS subjects.
After LRH administration, susceptible individuals, especially of group 1 had
exaggerated responses of LH, PRA, AT II and ALD as compared with the controls,
and a positive correlation was also found between peak levels of LH and AT II (r
= 0.54, P < 0.01). CONCLUSIONS: There is enhanced RAS function in PCOS especially
in group 1. This may contribute to the excess androgen production and high
incidence of ovarian hyperstimulation syndrome in this disorder.
PMID- 9639733
TI - [Endometrial cytology in normal postmenopausal women and during hormone
replacement therapy].
AB - OBJECTIVE: To explore the possibility of endometrial cyopathologic examination as
a method of monitoring endometrium during hormone replacement therapy (HRT) in
postmenopausal women. METHODS: Endometrial cells were taken via tubal aspiration
in 60 normal postmenopausal women (non-HRT group) and 41 with HRT for 3-18 months
(HRT group). Their morphologic changes were observed and compared by
cytopathologist. RESULTS: Atrophic endometrium was found in 51.7% of the non-HRT
group. Its proportion increased with age and the time after menopause.
Macrophages were seen in 68.3% of this group. However, in the HRT group the
occurrence of atrophic type and macrophage (12.2%, 7.0% respectively) was
significantly lower than that in the non HRT group (P < 0.05). Heterogeneity of
endometrial cell type was shown both in non-HRT (38.3%) and HRT (65.8%) groups.
CONCLUSIONS: Endometrial cells of postmenopausal women are not always atrophic in
appearance. They change significantly during HRT. Endometrial cytological
examination may be useful for monitoring during HRT.
PMID- 9639734
TI - [Induction of apoptosis in human ovarian cancer cell line HO-8910 by transforming
growth factor beta 1].
AB - OBJECTIVE: To investigate the mechanism of inhibitory effects of Transforming
Growth Factor beta 1 (TGF-beta 1) on human ovarian cancer cell in vitro. METHODS:
The possibility of induction of apoptosis in human ovarian cancer cell line HO
8910 cells after treatment with TGF-beta 1 was studied by using methods of DNA
electrophoresis, P1-staining, TdT-mediated dUTP-x nick end labeling and flow
cytometer assay (FCM); and the kinetic change of expression of c-myc was also
studied by relative quantified RT-PCR. RESULTS: DNA-strand nicks were present in
cells after treatment with TGF-beta 1 at the final concentration of 20 ng/ml for
36 hours. The percent of labeled cells reached 75.55% on the time of 48 hours, PI
staining-FCM assay also showed subdiploid peak of apoptotic cells at the same
time. The typical apoptotic DNA ladder was present in genomic DNA preparation
after treatment with TGF-beta 1 for 60 hours, meanwhile, the expression of c-myc
in cells started to decrease beginning at treatment for 9 hours. CONCLUSIONS: TGF
beta 1 can induce apoptosis in HO-8910; such an inductive effect may occur mainly
in G0/G1 phase. The effects of TGF-beta 1 on the inhibited expression of c-myc
and on the enhancement of cAMP concentration may also play important roles in the
process of apoptotic induction.
PMID- 9639735
TI - [Emphasizing clinical research on gynecological oncology].
PMID- 9639736
TI - [Summary of 5th National Symposium on Gynecological Oncology].
PMID- 9639737
TI - [Expression of glutathione S-transferase-pi in operative specimens as marker of
chemoresistance in patients with ovarian cancer].
AB - OBJECTIVE: To study the relationship between the expression of glutathione S
transferase-pi (GST-pi) in operative specimens and chemoresistance in patients
with ovarian cancer. METHODS: The expression of GST-pi in 87 epithelial ovarian
cancer tissues and 30 normal ovarian epithelial tissues was determined with
labelled streptavidin biotin method (LSAB). All the patients had not received
chemotherapy before operation. We used Chi-Square and Cox-Mantel test to analyze
the relativity between the expression of GST-pi and clinical pathological data,
chemotherapeutic response, prognosis in patients with ovarian cancer. RESULTS:
(1) 59 (67.8%) of 87 ovarian cancer tissue were demonstrated to be positive
expression with GST-pi, but all 30 normal ovarian epithelial tissue were
negative. (2) There was no direct correlation between the expression of GST-pi
and clinical pathological data. (3) 43 (43/59) of GST-pi positive cases were
chemoresistant, while only 3 (3/28) of GST-pi negative ones were chemoresistant.
(4) The difference in the chemotherapeutic response between the two groups was
obviously significant (P < 0.005). The survival period of the patients with GST
pi positive expression was also obviously shorter than that of those with GST-pi
negative expression (P = 0.004). CONCLUSION: These results strongly suggest that
GST-pi expression in epithelial ovarian cancer tissues is closely related to
chemoresistance clinically and it may be served as a useful marker to predict the
prognosis of patients.
PMID- 9639738
TI - [The relationship between multi-drug resistance gene expression and drug
resistance of ovarian carcinoma].
AB - OBJECTIVE: To study the relationship between multi-drug-resistance (MDR1) gene
expression and the drug resistance of ovarian carcinoma and the reversing potency
of drug-resistance modifying agent--cyclosporin A (CsA). METHODS: Tumor-bearing
mice of ovarian carcinoma cell (OVCA3) were divided randomly into three groups:
control group, adriamycin (ADM) group and ADM +CsA group. The tumor growth rate
and the survival rate of mice were investigated and compared among the groups. 32
frozen specimens of ovarian carcinoma tissue from patients were examined for the
expression of MDR1 gene by means of RT-PCR. RESULT: Ovarian carcinoma cells with
positive MDR1 gene expression showed cross drug-resistance to ADM, daunorubicin
(DNR), vincristine (VCR) and etoposide (VP-16), the value of inhibiting
concentration (IC50) is 4.1-15.5 times of that of the cells with negative MDR1
gene expression. To tumor-bearing mice, there was significant difference in tumor
growth rate between mice given combined therapy of CsA + ADM and those given ADM
only (P<0.01) Of the 32 frozen specimens of ovarian carcinoma tissue, there was
no confirmed relationship between MDR1 gene expression and the pathologic type or
differential grade. The possibility of poor prognosis of patients with positive
MDR1, gene expression was 16.07 (1.78-144.7) times of that of patients with
negative MDR1 gene expression. CONCLUSION: MDR-related drug can induce the
overexpression of MDR1 gene and result in the appearance of the multidrug
resistance phenomenon. CsA can partially reverse the multidrug resistance of
ovarian carcinoma cells both in vitro and in vivo. Detection of MDR1 gene
expression in patients of ovarian carcinoma could be used as an index to predict
the prognosis of the patients.
PMID- 9639739
TI - [Effects of herpes simplex virus thymidine kinase gene transduction and prodrug
on ovarian cancer cell].
AB - OBJECTIVE: To evaluate the efficacy of gene therapy with the herpes simplex virus
thymidine kinase (HSV-TK) gene transference followed by ganciclovir (GCV) therapy
in ovarian cancer. METHODS: HSV-TK gene was inserted into the hind III site of
pLNSX vector and recombinant plasmid (pLNS/HSV-TK) was constracted. Then, the
recombinant plasmid was transfered into PA317 packaged cell and the producer cell
line of recombinant retrovirus vector pLNS/HSV-TK was established. The
cytotoxicity efficacy of HSV-TK/GCV system to AO cell line was evaluated by
microcucture tetrajolium test (MTT) method. RESULTS: The recombinant retroviral
vector pLNS/HSK-TK can transfer HSV-SK gene into the genome of AO cell line and
make it sensitive to GCV. The growth inhibitory rate of AO cell line transfered
by pLNS/HSV-TK was 98.0% in the medium containing 400 mumol GVC. CONCLUSION: The
ovarian cancer cell line transfered by HSV-TK gene regressed rapidly in response
to the GCV therapy.
PMID- 9639740
TI - [Chemotherapy repeated injection via pelvic retroperitoneal cannulation].
AB - OBJECTIVE: To investigate the feasibility of chemotherapy for lymphatic
metastases of gynecologic cancer by repeated injection via pelvic retroperitoneal
cannulation. METHODS: 5-fluorouracil (5-FU), thiotepa, methofrexate were
repeatedly injected into the pelvic retroperitoneal space of 25 dogs and 24
patients respectively via cannulation. Microscope and high-performance liquid
chromatography were used to observe the drug concentration of 5-FU and pathologic
changes of the involved tissues. RESULTS: Animal experiment showed no toxicity to
vessels, ureter and the normal tissues involved; nodal 5-FU concentration of
repeated injection side was 7 to 9 times of that on the peripheral connective
tissue (P < 0.05). Clinical study revealed: (1) the external iliac, hypogastric,
obturator, deep inguinal and most of the common iliac lymph nodes were submerged
in the 5-FU solution; (2) pelvic and periaortic nodal 5-FU concentrations of
repeated injection side were 20 to 73 and 27 to 110 times of that on single
injection side respectively; nodal 5-FU concentration was 11 to 20 times of that
on the peripheral connective tissue; (3) metastatic cancer cells of nodal in the
study group showed obvious degeneration and necrosis while no changes in the
control; (4) no severe complications or adverse effects were observed.
CONCLUSION: Repeated injection via pelvic retroperitoneal cannulation was
feasible and probably more effective for the treatment of lymphatic metastases of
gynecologic cancer.
PMID- 9639741
TI - [Treatment and prognostic factors of epithelial ovarian cancer].
AB - OBJECTIVE: To study the treatment results and prognostic factors of epithelial
ovarian carcinoma. METHODS: Retrospective study of 155 cases of ovarian
epithelial carcinoma admitted in our hospital since Jan. 1970 to Dec. 1992. All
of these cases had postoperative pathological diagnosis and staging according to
FIGO. 42 cases had second operations and 4 cases had the third. 149 cases had
postoperative chemotherapies except for 6. Chemotherapies were also given to 32
cases after the second operation, while 9 for recurrence. RESULTS: The 2-year, 5
year, 10-year survival rates of stage I were 92.4%, 87.0%, 70.6%; and II 91.9%,
63.6% 47.8%; III 59.9%, 38.2%, 19.2% and IV 25.0%, 25.0%, 0.0% respectively. All
6 cases without chemotherapy after surgery died within 2 years. The results
indicated that the prognosis of ovarian epithelial carcinoma was related to
clinical stage, cellular grade and tumor residues. The 5-year survival rates for
stage I was 87.0% and III 38.2% (P < 0.001); and cell G1 95.0% and G3 11.8% (P <
0.001), while no residual tumor 97.6% and with residual tumor > 2cm 21.2% (P <
0.001) respectively. CONCLUSION: Residual tumor of ovarian epithelial carcinoma <
2cm after primary surgery and chemotherapy right after surgery can improve
survival rates.
PMID- 9639742
TI - [Immunohistochemical locating and quantitative studies of 5-hydroxytryptamine and
5-hydroxytryptamine receptor in placental villi of patients with pregnancy
induced hypertension].
AB - OBJECTIVE: To supply evidence of relationship between pregnancy induced
hypertension (PIH) and 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine
receptor (5-HTR) synthesized by placental villi. METHODS: Five normal placentas
and 15 placentas of PIH were used for studying localization and quantification of
5-HT and 5-HTR in placental villi by using immunohistochemical and in situ
quantitative methods. RESULTS: Syncytiotrophoblasts and capillary endothelium in
placental villi of control group showed 5-HT and 5-HTR positive immunoreaction,
but in placental villi of group with PIH, syncytiotrophoblasts appeared 5-HT and
5-HTR weak positive immunoreaction and capillary endothelium appeared 5-HT and 5
HTR weak positive or negative immunoreaction. The results of in situ quantitation
showed that the content of 5-HT and 5-HTR in placental villus
syncytiotrophoblasts of group with PIH were significantly lower than those in the
control group. CONCLUSIONS: The content of 5-HT and its receptor in placenta may
be related to PIH.
PMID- 9639743
TI - [Changes of concentrations of umbilical blood monoamines in low birth weight
infant and their clinical significance].
AB - OBJECTIVE: To investigate the changes of concentrations of umbilical blood
monoamines in low birth weight (LBW) infants and their clinical significance.
METHODS: By fluorescence spectrophotometry, the concentrations of umbilical
plasma norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5
hydroxyindoleacetic acid (5-HIAA) in 18 LBW before and after delivery were
measured and compared with 20 normal birth weight (NBW) infants. RESULTS: The
concentration of all monoamines, especially of the 2 catecholamines, i.e. NE and
DA, were markedly lower in LBW than that in NBW (P < 0.05-0.01), regardless of
prepartus or postpartus; the concentrations of all monoamines in postpartal
umbilical plasma in both of LBW and NBW were higher than those in prepartal, and
the increase of NE in NBW showed significant difference (P < 0.05). CONCLUSIONS:
The decrease of all monoamines, especially of catecholamines in LBW could be one
of the reasons causing the increase of mortality and the decrease of mental and
physical development in LBW.
PMID- 9639744
TI - [Insulin growth factor I in the development of ovarian follicles].
AB - OBJECTIVE: To investigate the role of insulin growth in factor-1 (IGF-1) in the
development of ovarian follicles under the stimulation of gonadotropins in an in
vitro fertilization (IVF) program. METHODS: Radioimmuoasssy was used to determine
the levels of sex hormones and IGF-1 in the serum and follicular fluid samples.
In situ hybridyzation was used to detect the expression of IGF-1 and IGF-1
receptor (IGF-1R) in the granulosa cell obtained from follicular aspiration in
women undergoing IVF egg retrieval procedures. RESULTS: (1) Levels of plasma IGF
1 increased with the development of follicles (P < 0.001); follicular fluid (FF)
IGF-1 levels were lower than those of matched plasma; FF-IGF-1 decreased with
increase of follicle numbers (P < 0.01), e.g. in patients with less than 2
follicles (diameter > or = 15 mm) at the tine of ovum pick-up the FF-IGF-1 levels
were much higher than patients with more than 2 follicles (P < 0.05). (2)
Significant negative correlation was found between plasma IGF-1 and plasma E2 and
also between FF-IGF-1 and FF-follicle-stimulating hormone (FSH) during ovum pick
up (P < 0.01). (3) IGF-1 mRNA was not, while IGF-1R mRNA was found to be present
in the human granulosa cells taken at ovum pick-up. CONCLUSIONS: Plasma IGF-1
production might be stimulated by gonadotropins and distributed into the ovarian
follicles by diffusion from peripheral circulation, acting upon the granulosa
cells and therefore plays a complementary role with the gonadotropins in the
regulation of follicular development.
PMID- 9639745
TI - [Responses of growth hormone and prolactin to L-Dopa in women with polycystic
ovarian syndrome].
AB - OBJECTIVE: To evaluate the altered dopaminergic modulation of growth hormone (GH)
and prolactin (PRL) in polycystic ovarian syndrome (PCOS). METHODS: Responses of
GH and PRL to L-Dopa (L-DA) (500 mg) were observed in two PCOS groups (LH/FSH >
or = 3, Group I, n = 15, LH/FSH < 3, Group II, n = 15) and the control (n = 20).
RESULTS: Significantly lower GH (P < 0.01) and higher PRL levels (P < 0.05 in
group I) in the basal state, and lower responses of GH and PRL to L-DA were found
in two PCOS groups as compared with the control. CONCLUSION: The altered basal
levels and blunted L-DA evoked responses of GH and PRL suggest a relative
decrease of the dopaminergic activity in PCOS patients.
PMID- 9639747
TI - [The risks and benefits of hormone replacement therapy in postmenopausal women].
PMID- 9639746
TI - [Small cell carcinoma of the cervix].
PMID- 9639748
TI - [Prevention and treatment of postmenopausal osteoporosis].
PMID- 9639749
TI - [Summary of the National Symposium on Menopausal and Postmenopausal Problems].
PMID- 9639750
TI - [The shrinkage of ovarian and uterine size and the decline of serum estradiol
level in post-menopausal women].
AB - OBJECTIVE: To investigate the shrinkage of ovarian and uterine size, and the
decline of serum estradiol (E2) level in normal women. METHODS: Ovarian and
uterine area of 92 perimenopausal and 292 postmenopausal women, measured by
transvaginal ultrasonography, were analysed retrospectively and were compared
with those of the controls consisting of 41 normal women in midfollicular phase,
so did the serum E2 levels. RESULTS: As compared with the control group, ovarian
area and endometrium thickness shrunk on an average of 30%, 2% and 56%, 48% in
early perimenopausal and postmenopausal groups respectively. Serum E2 level and
uterine area increased by 11% and 38% in early perimenopausal group, but
decreased by 67% and 21% in postmenopausal groups respectively. No obviously
further decline of serum E2 level was found 1 year after menopause, and of
ovarian, uterine area 3-5 years after menopause. CONCLUSION: These data represent
a normal profile of ovarian and uterine shrinkage and decline of serum E2 levels
related to the time of menopause.
PMID- 9639751
TI - [The effects of ethinyl estradiol on glucose metabolism in postmenopausal women].
AB - OBJECTIVE: To study the effects of ethinyl estradiol on glucose metabolism in
postmenopausal women. METHODS: Postmenopausal women were randomized as nine cases
(group A) receiving 0.025 mg ethinyl estradiol (EE) and ten cases (group B)
receiving EE 0.05 mg for three months. The oral glucose tolerance test (OGTT) and
frequently sampled intravenous glucose tolerance test (FSIGT) were performed
before and after EE respectively. The levels of plasma glucose, insulin were
measured and the area under curve (AUC) and insulin sensitivity indexes (SI) were
calculated. RESULTS: Both two dosages of EE administration effectively decreased
the levels of fasting plasma glucose and insulin and significantly reduced the
AUC of insulin. SI was increased significantly. There were no significant
differences in AUC of glucose before and after treatment in group A, but in group
B the AUC of glucose significantly increased after treatment. CONCLUSIONS: EE may
significantly reduce the levels of fasting plasma glucose and insulin
concentrations and abate the insulin resistance in postmenopausal women; 0.05 mg
EE possibly causes the deterioration in glucose tolerance, suggesting the use of
0.025 mg EE as an appropriate dosage.
PMID- 9639752
TI - [Relative contribution of ageing and menopause to the changes of lumbar bone
density in 1,400 Beijing women].
AB - OBJECTIVE: To study the pattern of bone mass changes in women's lumbar spine and
obtain evidence to guide the prevention of postmenopausal osteoporosis. METHOD:
Bone mineral content (BMC) and bone mineral density (BMD) of lumbar 1-4 in 1 400
Beijing women aged 20-85, were measured by dual energy X-ray absorptiometry.
RESULTS: (1) Both BMC and BMD increased after age 20, reached the peak at the age
of 30, and decreased significantly after the age of 50; (2) There was no
significant change of BMC and BMD after the age of 25 in premenopausal women.
Bone loss accelerated in the first 10 years after menopause. Women who
experienced menopause early had lower bone mass. (3) The prevalence of
osteoporosis in 1 121 postmenopausal women was 17.40%. CONCLUSION: Significant
bone mass loss of lumbar spine occurs during the first decade following
menopause, which is the key period for preventing osteoporosis.
PMID- 9639753
TI - [Prevention of bone loss by chlorotrianisene in oophorectomized rats].
AB - OBJECTIVE: To determine the influence of chlorotrianisene on bone metabolism in
oophorectomized rats. METHODS: Forty-eight Wistar female rats, 70 days of age,
were randomly divided into four groups: SV group (sham operation + vehicle), OV
group (oophorectomy + vehicle), SE group (sham (operation + chlorotrianisene) and
OE group (oophorectomy + chlorotrianisene). Chlorotrianisene or vehicle 4 ml/kg
was given i.p. daily for 45 days from day 7 of being ovariectomized or sham
operated. At the time of death, uterine weight was measured, and the thoracic
vetebra 12, left tibia were collected and made into decalcified bone specimens
for histomorphometry. RESULTS: There were significant difference in the uterine
weight among each group. Significant different appearance by bone
histomorphometry was seen between OV and the other three groups, but not shown
between SV and SE, OE groups. CONCLUSION: These results suggest chlorotrianisene
could inhibit bone loss and delay the atrophy of uterus induced by ovariectomy in
Wistar female rats. It has protective effects on bone like other estrogen
preparations.
PMID- 9639754
TI - [Effects of progesterone on proliferation and differentiation of fetal rat
calvarial osteoblasts in vitro].
AB - OBJECTIVES: To investigate the influence of progesterone on proliferation and
differentiation of osteoblast at the levels of gene expression and cell
functions. METHODS: Fetal rat calvarial osteoblasts were cultured in vitro in the
presence of (10(-9) mol/L-10(-6) mol/L) progesterone. Cell proliferation,
alkaline phosphalase (ALP) activity, osteocalcin mRNA expression and osteocalcin
secretion in the medium and bone nodule formation were analyzed. RESULTS:
Progesterone did not influence cell proliferation; Progesterone enhanced the ALP
activity in rat osteoblasts; Progesterone stimulated osteocalcin mRNA expression
in a dose-dependent manner and increased the amount of osteocalcin in the culture
medium; Progesterone increased both number and area of bone nodule formation.
CONCLUSION: Progesterone has a multi-stimulating effect on the differentiation of
fetal rat calvarial osteoblast, hut no effect on cell proliferation.
PMID- 9639755
TI - [Relationship between human parvovirus B19 infection and spontaneous abortion].
AB - OBJECTIVE: To determine whether there is a relationship between parvovirus B19
infection and spontaneous abortion. METHODS: 105 embryo tissues from spontaneous
abortions of unknown cause during 1994-1995 were studied using nested polymerase
chain reaction (PCR) assay for parvovirus B19 DNA. As controls 40 fetal tissues
were also examined. Among which, 20 were collected from induced abortions, and
the others were stillbirths. The positive specimens underwent further study for
TORCH infections. RESULTS: 26 (24.5%) were B19 DNA positive in the case group and
2 (5.0%) in the control group. The difference was significant (P < 0.05). Among
26 positive specimens, 5 had cytomegalovirus (CMV) infection as well as 2 had
both CMV and herpes simplex virus (RSV) infections. CONCLUSIONS: Parvovirus B19
infection may be an important pathogen for spontaneous abortion, and it is
suggested to investigate parvovirus B19 infection among pregnant women in China.
PMID- 9639756
TI - [Histomorphometric study of the effect of nylestriol on bone turnover in
ovariectomized rabbits].
AB - OBJECTIVE: To assess the effect of Nylestriol on postmenopausal osteoporosis in
an attempt to reveal its mechanism. METHODS: Thirty-seven month-old female New
Zealand white rabbits were randomized into 3 groups (10 rabbits per group):
treatment group [ovariectomized (OVX) + nylestriol (2 mg, monthly)], OVX control
group (OVX + vehicle) and normal control group (sham operation + vehicle). Six
months later, all rabbits were subjected to tetracycline labelling and then were
killed. Under VIDAS system, bone turnover was assessed by bone histomorphometry.
RESULTS: Bone volume trabecular (BV/TV), relative osteoid volume (OV/BV),
osteoblastic index (OBI) and bone formation rate at tissue level [BFR(T)]
increased in treatment group compared with OVX control group and (or) sham
control group. CONCLUSIONS: Nylestriol can increase the number of osteoblast,
which resulted in more bone matrix production and consequently converted the bone
turnover of OVX rabbits to a positive balance situation. It indicated that
Nylestriol was probably a stimulator for osteoblast recruitment and (or)
proliferation.
PMID- 9639757
TI - [The clinical and pathological characteristics of epithelial ovarian carcinoma in
patients with age under 40].
AB - OBJECTIVE: To investigate the clinical and pathological characteristics of
epithelial ovarian carcinoma in patients with age under 40. METHODS: From Jan
1978 to Dec 1992, 54 cases with epithelial ovarian carcinoma under 40 years old
were admitted to our hospital and enrolled in the study group, another 54
patients suffered from the same disease with age over 40 in the same period were
served as control. Comparison analysis for clinical and pathologic data of 2
groups was performed using SPSS and SURVALC statistics software. RESULTS: Main
complaint because of either pelvic mass or abdominal mass found by chance was
more common in study group (46.3%) than that in control group (27.8%). whereas
because of symptoms was less common in study group (53.7%) than in control group
(72.2%). Other parameters such as early stage (I and II) rate (61.1%), unilateral
tumor rate (68.5%), average maximum diameter of tumor (13.6 cm), highly
differentiated rate (50%) and the possibility for tumor reductive surgery were
higher in study group than in control group. The difference of histological
pattern and chemotherapy between 2 groups was not significant. Single variate
analysis showed that the prognosis was better in study group. The 2-year and 5
year survival rates were 69.8% and 50.2% respectively. No recurrence was found in
the 8 patients in whom the contralateral healthy ovary remained. However multiple
variate analysis indicated that age was not a prognostic factor. CONCLUSION:
Epithelial ovarian carcinoma was prone to be lower degree malignancy in patients
under 40 years therefore the prognosis of them was better. It might be resonable
to have healthy ovary left in some select cases.
PMID- 9639758
TI - [Pregnancies complicated by human B19 parvovirus infection: prevention and
treatment].
PMID- 9639759
TI - [Pregnancy and hypertension].
PMID- 9639760
TI - [Current status and trends of prenatal gene diagnosis].
PMID- 9639761
TI - [Rapid prenatal diagnosis of Down's syndrome in the first trimester of pregnancy
by fluorescence in situ hybridization].
AB - OBJECTIVE: To assess whether fluorescence in situ hybridization (FISH) with
chromosome 21, specific DNA probe is applicable as a prenatal diagnostic tool for
Down's syndrome. METHOD: We used FISH with chromosome 21 specific probe on 30
uncultured chorionic villi cell samples to detect the Down's fetus, and we also
performed the conventional chromosome analysis of chorion cells from parallel
samples. RESULTS: In samples with disomic karyotype, an average of 1 percent (0-5
percent) of the nuclei had three hybridization signals. By contrast, in the
samples of trisomy 21 fetus, an average of 86 percent (78-91 percent) of the
nuclei displayed three signals. CONCLUSION: FISH can provide a rapid and accurate
method for the first trimester prenatal diagnosis of Down's syndrome.
PMID- 9639762
TI - [Prenatal screening for major fetal defects by using of maternal serum markers].
AB - OBJECTIVE: To investigate the effect of second-trimester maternal serum markers
AFP, beta-hCG, uE3, for prenatal screening of the fetal defects. METHODS: In 677
women the triple markers were measured. Some factors that may affect the testing
such as maternal weight, gestational age, were adjusted on analyzing the result
of the testing. Each woman, who underwent the triple screening, will be followed
up until her fetus was delivered. RESULTS: Among the women who were screened, 11
patients who presented at least one marker positive were identified as having an
abnormal fetus, and the positive rate was 1.6%. While 32 women were confirmed to
be false positive with a rate of 4.7%. Another 11 women had fetal demise on
second-trimester, which had been proved to be not caused by fetal abnormality.
CONCLUSION: Maternal triple serum markers may take as a routine protocol for
prenatal screening of the fetal defects.
PMID- 9639763
TI - [The human SRY gene for prenatal diagnosis].
AB - OBJECTIVE: To establish the method for prenatal sex diagnosis of the fetus
carrying sex-linked genetic disorder. METHOD: Human SRY gene was amplified by
polymerase chain reaction. A 422-bp male specific fragment was obtained. RESULTS:
The fragment was identified in 10 men, but unidentified in 10 women. The
diagnostic accordance rate of 20 amniotic fluid samples was 100%, 22 of 47
chorionic villi samples were positive. The rate of positive/negative (22/25) was
nearly the sex rate of newborn babies. In the meantime, direct-PCR amplification
of blood and amniotic fluid was completed. The fragment was shown from 4
microliters to 0.5 microliters of blood and from 2 ml to 0.5 ml of amniotic
fluid. CONCLUSION: The results show that fetal sex determination by PCR will be
suitable for clinical prenatal diagnosis of sex-linked genetic disorders.
PMID- 9639764
TI - [AFP, uE3, beta-hCG levels applied for prenatal diagnosis of Down's syndrome].
AB - OBJECTIVE: To investigate the relationship between fetal trisomy 21 and alpha
fetoprotein (AFP), unconjugated oestriol (uE3) and beta human chorionic
gonadotropin (beta-hCG) levels in maternal serum, amniotic fluid and fetal serum.
METHOD: AFP, uE3 and beta-hCG levels in maternal serum, amniotic fluid and fetal
serum from 17 pregnancies with fetal trisomy 21 and 131 unaffected control
pregnancies were measured between 16 to 28 weeks gestation using
radioimmunoassay. RESULTS: In these pregnancies with fetal trisomy 21, the AFP
and uE3 levels in maternal serum, amniotic fluid and fetal serum were lower than
those in controls; but beta-hCG levels were higher (P < 0.05). CONCLUSION: To
measure maternal serum AFP, uE3 and beta-hCG levels will be useful in prenatal
detection of trisomy 21.
PMID- 9639765
TI - [Clinical observation on Doula delivery].
AB - OBJECTIVE: To improve the obstetricare quality during labour and delivery, our
hospital carried out Doula delivery which is an appropriate technology in
promoting natural delivery reported by Dr M Klaus, USA. METHODS: Mothers were
accompanied by senior experienced midwife who afforded continuous physical,
psychological and emotional support during the whole course of labour. From April
to August 1996, 46 cases of primigravida were selected as study group. Another
336 primigravida given birth in the same period were taken as controls, who were
accompanied by their family member during their active phase of labour. RESULTS:
The results showed that the cesarean section rate was 6.5% in Doula group while
20.8% in the control group. The difference was significant (P < 0.05). The
duration of labour and volume of postpartum bleeding both declined obviously in
the study group (P < 0. 05). CONCLUSION: Doula delivery offered better quality of
health care during labour and decreased cesarean section rate duration of labour
and postpartum bleeding.
PMID- 9639766
TI - [Histochemical localization of nitric oxide synthase in the human placenta].
AB - OBJECTIVES: To study localization, distribution and activity of nitric oxide
synthase (NOS) in the human placenta and to speculate the action of nitric oxide
(NO) during pregnancy. METHODS: NADPH-diaphorasc histochemical method was used to
indicate the distribution, localization and activity of NOS in the placentae of
normal term pregnancy (n = 21). Severe pregnancy induced hypertension (PIH) (n =
15), intrauterine growth retardation (IUGR) (n = 2) and villi of early pregnancy
(n = 16). RESULTS: The NOS reactive product called blue formazan was found in
most of syncytiotrophoblast (STr) and located in top of cells in severe PIH and
IUGR placentae. In normal term placentae the blue formazan was found in STr and
located in base of cells. The number of blue formazan was more than that of PIH
and IUGR placentae. Endothelial cells of most capillaries of the terminal villi
in severe PIH and IUGR placentae were found to be deposited with blue formazan,
but in normal term pregnancy, blue formazan was found only on rare occasion.
CONCLUSION: Distribution and localization of NOS in placentae of normal term
pregnancy, severe PIH and IUGR cases and early villi are specific. The NOS
activity of STr in severe PIH placentae and IUGR placentae are lower than that of
normal term placentae. The distribution and localization of NOS within the STr in
severe PIH placentae and IUGR placentae are different from those in normal term
placentae. The low activity of NOS secreted by placenta may be relative to the
pathogenesis of PIH and IUGR.
PMID- 9639767
TI - [Comparison of misoprostol and ricinus oil meal for cervical ripening and labor
induction].
AB - OBJECTIVE: To compare the safety and efficacy of intravaginal prostaglandin E1,
misoprostol with ricinus oil meal for labor induction. METHODS: Sixty patients
with an indication for induction of labor were randomly assigned to two groups
(30 cases each) induction with misoprotol, 50 micrograms intra-vaginally every 3
hours until active labor, or with that ricinus oil meal was taken. RESULTS: The
time from start of induction to vaginal delivery was significantly shorter in the
misoprostol group (12.2 vs 18.1, P < 0.05), and fewer patients in the misoprostol
group required oxytocin augmentation (10.0% vs 40.0%, P < 0.05). The mean change
in the Bishop score was significantly higher in those receiving misoprostol (5.5
vs 3.1, P < 0.05). Uterine tachysystole occurred more frequently in patients in
the misoprostol group (16.7%) than in the ricinus oil meal group (3.0%). No
significant differences were noted in the mode of delivery and patients of
successful labor induction. CONCLUSIONS: Vaginally administered misoprostol is an
effective agent for the cervical ripening and induction of labor.
PMID- 9639768
TI - [The value of blood sedimentation test in early diagnosis of amniotic fluid
embolism].
AB - OBJECTIVE: To explore the value of peripheral blood sedimentation in early
diagnosis of amniotic fluid embolism. METHOD: The contents of amniotic fluid were
detected with blood sedimentation test in 15 cases of amniotic fluid embolism and
100 cases of normal pregnant women. RESULTS: The contents of amniotic fluid
including particles of vernix caseasa, lanugo hair and epithelium cells were
found in serum of amniotic fluid embolism cases but not found in cases of normal
pregnant women. CONCLUSION: It suggested that the blood sedimentation test would
be valuable for early diagnosis of amniotic fluid embolism.
PMID- 9639769
TI - [The changes of T lymphocyte subsets and serum interleukin-2 receptor in
peripheral blood of the pregnant women complicated by systemic lupus
erythematosus].
AB - OBJECTIVE: To determine the changes of T lymphocyte subsets, natural killer (NK)
cell and serum interleukin-2 receptor (SIL-2R) in peripheral blood of the
pregnant women with systemic lupus erythematosus (SLE). METHODS: T lymphocyte
subsets NK cell, and SIL-2R in peripheral blood were detected by flow cytometry
(FCM) and enzyme-labeled immunosorbent assay (ELISA) in 14 cases of pregnant
women complicated by SLE (SLE+NP), 18 cases of stationary phase SLE (SLE), 20
cases of normal non-pregnant women (NNP) and 20 cases of normal pregnant women
(NP). RESULTS: The percentages of CD4+ cell were decreased significantly in
SLE+NP group as compared with the other three groups (P < 0.01); and the ratio of
CD4+/CD8+ was decreased significantly in SLE+NP group, as compared that in SLE
group and in NNP group (P < 0.01). There were no difference in the number of NK
cells among the four groups. The SIL-2R values were found to be increased
significantly in the SLE+NP group, as compared with that of other three groups (P
< 0.01). CONCLUSION: The observation on the changes of peripheral T lymphocyte
subsets and SIL-2R may be helpful for monitoring progress of SLE during
pregnancy.
PMID- 9639770
TI - [Immunohistochemical study on the decidua vessels in recurrent spontaneous
abortion].
AB - OBJECTIVE: To investigate the effects of uterine local immunological factors in
recurrent spontaneous abortion (RSA). METHODS: The decidua vessels were studied
by immunohistochemical ABC method in 26 cases of RSA and 10 cases of normal
pregnant women (control group). Meanwhile, serum IgG, IgM, IgA, C3 and CH50 were
determined in RSA group and in control group. RESULTS: In RSA cases, the
depositions of IgM (17 cases, 80.8%) were significantly increased (P < 0.001,
respectively) as compared with the control group, the depositions of IgG (2
cases, 7.8%) were significantly decreased (P < 0.001); the levels of serum C3,
CH50 were significantly decreased (P < 0.01 respectively), but the level of serum
IgA was increased significantly (P < 0.05) as compared with the control group.
The depositions of C3 were significantly increased in RSA who had autoantibodies
(P < 0.01), as compared with those without autoantibodies. In addition, the
positive stain of IGM and C3 in the cytoplasm and nuclei of decidua cells and in
the cytoplasm of gland cells of some RSA patients were also observed. CONCLUSION:
The results suggest that the immunological damage of decidua vessels is a very
important factor in immunopathogenesis for RSA. Decidua cells and gland cells may
have potential immunological function.
PMID- 9639771
TI - [Carcinoma metastatic to the cervix: a study of 19 cases].
AB - OBJECTIVES: To report the clinical features and to evaluate the treatment results
of 19 cases of cervical metastatic carcinoma. METHODS: We analyzed
retrospectively the 19 patients with carcinoma metastatic to the cervix treated
during the period of 1959 to 1994 at Cancer Hospital, Chinese Academy of Medical
Sciences. RESULTS: The average age of patients was 43.7. The main symptom was
irregular vaginal discharge and (or) bleeding. In most patients, the primary
cancers originated from digestive tract or ovary. The treatment methods included
radiotherapy alone, radiotherapy combined with chemotherapy after operation, and
surgery plus radiotherapy. The 1-, 2- and 5-years survival rates (life-time table
were 68.5%, 47.3% and 26.2% respectively, and the longest period for survived
patient with dysgerminoma has lived was more than 22 years. CONCLUSION: The
active proper treatment of primary cancer can prolong the survival time of
patients with carcinoma metastatic to the cervix. The patients whose metastatic
lesions are limited to the cervix and sensitive to the radiation may be cured by
radiotherapy and combination therapy.
PMID- 9639772
TI - [Prenatal screening for Down's syndrome].
PMID- 9639773
TI - [Gene diagnosis of fragile X syndrome].
PMID- 9639774
TI - Effect of dexamethasone on Glu-IR and GABA-IR neurons of hippocampus in rats.
AB - Dexamethasone (Dex) was injected into the rat lateral ventricle and the changes
of glutamate-immunoreactivity (Glu-IR) and gamma-aminobulyric acid
immunoreactivity (GABA-IR) neurons in the hippocampus were immunocytochemically
examined 2 h after injection. The results showed that Glu-IR neurons increased
and GABA-IR neurons did not show marked change. The mechanism remains to be
further studied.
PMID- 9639775
TI - Mechanism of anti-beta-adrenoceptor antibody mediated myocardial damage in
dilated cardiomyopathy.
AB - Antibodies against beta(1)-adrenoceptor can be detected in serum of patients with
dilated cardiomyopathy (DCM), which have beta-agonist-like activity, and induce a
positive chronotropic effect on cardiac myocytes by its persistence at full
strength. Effects of the antibodies against beta-adrenoceptor from sera of
patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca(2+)
concentration ([Ca2+]i) were observed in the cultured single layer SD rat
ventricular cells by using the cytotoxicity assay and fluorescent Ca(2+)
indicator fura-2/AM. The positive sera of the anti-beta-adrenoceptor antibodies
from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a beta(1)
receptor blocker, might inhibit the increase of the antibody-mediated myocardial
[Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i.
Our results suggest that the anti-beta-adrenoceptor antibody might increase
myocardial [Ca2+]i and result in myocardial damage. The antibodies might activate
receptor-gating Ca(2+)-channel, thereby causing myocardial [Ca2+]i rise and
calcium overload. Early use of betaloc is recommended in the treatment of dilated
cardiomyopathy.
PMID- 9639776
TI - Effects of ligustrazine on bone marrow microvessel system in the early period of
acute radiation injury in mice.
AB - Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine
Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow
microvessels of the Ligustrazine group was much greater than that of the control
group. On the 7th day, the amount of the control group decreased to normal, while
the ligustrazine group was still increasing, and the microvessel area was
enlarged obviously.. The percentage of the hematopoietic tissue volume in bone
marrow between the two groups had no significant difference in the first 7 days.
On the 7th day after irradiation, the peripheral neutrophilic granulocytes
increased in the Ligustrazine group. The results suggested that early use of
Ligustrazine after acute radiation injury might improve the blood supply of bone
marrow, and be helpful for recovery of hematopoiesis.
PMID- 9639777
TI - Effect of concurrent use of rh-IL-3 and rh-GM-CSF on apoptosis of HL-60 cells
induced by Ara-C.
AB - The myeloid leukemic cell line HL-60 was studied by using DNA gel
electrophoresis, flow cytomery, McAb C-myc, McAb Bcl-2 and CFU-L. From zero to 36
h, the apoptosis rates of 8 different phases and other indexes were observed. The
results showed that with the prolonged time of drug incubation, apoptosis of HL
60 cells increased progressively. This effect can be enhanced obviously by rh-IL
3 and rh-GM-CSF. At the same time, the killed rate of leukemic cells by Ara-C
induction was increased. C-myc expression was decreased and Bcl-2 expression did
not display apparent change. Interestingly, the normal hemopoietic cells were not
affected by these two kinds of cytokine. The theoretical basis was provided for
concurrent use of rh-IL-3, rh-GM-CSF and cytotoxic drugs whose purpose is to
elevate remission rate during the phase of induced remission of leukemia.
PMID- 9639779
TI - Redistribution of platelet membrane glycoprotein IV and release of intracellular
alpha-granule thrombospondin in patients with chronic myelogenous leukemia.
AB - The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of
intracellular alpha-granule thrombospondin (TSP) were examined and the inhibition
of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in patients with
chronic myelogenous leukemia (CML) was observed and quantitation of beta-TG and
PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080 +/- 17010
molecules/platelet as compared with 13190 +/- 4810 from the controls (P < 0.01).
No abnormality was found in the distribution of platelet membrane GPIb and
GPIIb/IIIa (P > 0.05). The GPIV redistribution on active platelet membrane
induced thrombin (IU/ml) from CML and healthy donors was 44320 +/- 32310 and
22800 +/- 12700 molecules/platelet respectively (P < 0.01). The difference in the
release of intracellular alpha-granule TSP between CML and the control group was
not found (P > 0.05). There was no direct correlation between GPIV expression and
TSP binding after platelet activation. The high levels of beta-TG and PF4 in sera
inhibited release of intracellular alpha-granule TSP in vitro. These results
indicate that the abnormality of platelet membrane GPIV is a common marker in
CML, therefore the specific increase of platelet GPIV in patients with CML may be
a useful tool for the diagnosis and monitoring of the platelet dysfunction. The
release of internal TSP pools is hindered by either beta-TG or PF4 in sera.
PMID- 9639778
TI - Study on immunoregulation by interleukin-1 receptor antagonist in NZB/W F mice.
AB - The immunoregulating effect of Interleukin-1-receptor antagonist (IL-1ra) in
lupus-like NZB/W F1 mice was investigated to find possible approach to prevent
lupus nephritis. 12 female NZB/W F1 mice of 13 weeks were randomly divided into 2
groups. Each mouse in the treated group was intraperitoneally injected with IL
1ra once every 2 weeks for 3 times at the dosage of 100 micrograms each time,
while the control group was given injection of 0.1 ml normal saline. All the mice
were killed at the age of 9 months and the immunologic function was examined.
Results showed that this dosage could not completely prevent the development of
lupus nephritis, but the renal damage was alleviated and the urine protein was
decreased. Moreover, it could improve the immunofunction by significantly
reducing the levels of serum IL-1 and obviously increase the activities of NK
cells and IL-2 induced by ConA in mononuclear cells of spleen. There was no
significant difference in the levels of serum IL-6 and TNF-alpha between the
treated group and control group. It is concluded that IL-1ra has certain
regulatory effect on the immunologic function of lupus-like NZB/W F1 mice.
PMID- 9639780
TI - Nitric oxide synthase activity in arterial tissues of cirrhotic rats.
AB - The changes in the activities of constitutive nitric oxide (NO) synthase (cNOS)
and inducible NOS (iNOS) were investigated in arterial tissues of CCl4-induced
cirrhotic adult SD rats. The aortic tissue homogenate were prepared in normal and
cirrhotic rats. NOS activity was measured by conversion of 3H-arginine to 3 H
citrulline. The activities of cNOS and iNOS were calculated in terms of presence
or absence of Ca2+. The results showed that activities of total NOS, cNOS and
iNOS in arterial tissues were all increased significantly in cirrhotic rats as
compared with those in normal controls. There was a significant positive
correlation between the activities of total NOS and cGMP content in cirrhotic
arterial tissues.
PMID- 9639781
TI - Expression of matrix metalloproteinase-9 mRNA in osteoporotic bone tissues.
AB - Matrix metalloproteinases (MMPs), a sort of important enzymes involved in
extracellular matrix metabolism, play critical roles in the process of tissues
remodeling, wound healing and metastasis of tumors. Dot blot and in situ
hybridization were used in this study to detect the expression and localization
of MMP-9, an important proteolytic enzyme implicated in bone resorption in bone
tissues. The results showed that the level of MMP-9 mRNA expression in
osteoporotic bone tissues was significantly higher than that in normal control
group and the cell types that expressed MMP-9 mRNA included mono- and multi
nuclear osteoclasts and some lining cells on the surface of bone matrix. It was
suggested that MMP-9 play a key role in the development of bone loss in
osteoporosis.
PMID- 9639782
TI - Bipolar esophageal electrocardiography by using standard limb leads.
AB - The ear-xiphisternum distance (EXD, the distance from the low edge of the ear to
the xiphisternal basis in supine position) was used as a reference value for
esophageal catheter insertion. ECGs recorded in the esophagus with bipolar
electrocardiography using standard limb lead (ESLL) and conventional unipolar
lead (ECUL) were compared. 112 patients with sinus rhythm and 76 patients during
paroxysmal supraventricular tachycardia (PSVT) whose P-wave and QRS complex did
not overlap were studied. The results suggested that in sinus rhythm the
amplitude of the P-wave in ESLL was larger and the T-wave was smaller than in
ECUL. During PSVT, the P-wave was much clear and higher in each lead of ESLL than
that in ECUL. The ideal range of esophageal ECG recording was situated between
the end of EXD and 6.5 cm proximal to it.
PMID- 9639783
TI - Experimental study on the effects of aprotinin on myocardial ischemia and
reperfusion.
AB - Direct effects of a high-dose aprotinin on the normally perfused hearts and the
myocardial protection after ischemia and reperfusion were investigated in an
isolated working rat heart model. In trial I, hearts had no ischemia and were
perfused with either K-H solution or the K-H solution containing aprotinin (200
KIU/ml) for 55 min. No statistically significant difference was observed in
hemodynamics between the two groups. In trial II, hearts were exposed to 150 min
period of global ischemia at 15 degrees C with 4 degrees C multidose St. Thomas'
II solution (STS). The control group I received normal K-H solution; the group II
was treated with the solution with aprotinin added. The group III was similar to
the group I and received the STS enriched with aprotinin. On reperfusion, the
recovery of hearts in group III was significantly better than those of the group
I and II, as reflected by better hemodynamics and myocardial ATP levels and
milder myocardial ultrastructural injury. There was no difference between the
group I and II. These results suggest that the aprotinin a dose of 200 KIU/ml has
no harmful effects on normally perfused hearts and has a marked myocardial
protective effect on the prolonged myocardial ischemia when used in cold
crystalloid cardioplegia.
PMID- 9639784
TI - Effect of intra-arachnoid space perfusion on thromboxane A and prostacycline in
experimental spinal cord injury.
AB - In order to understand the relation between TXA2-PGI2 and secondary trauma and
the effect of intra-arachnoid perfusion of dexamethasone and verapamil on
alteration of TXA2-PGI2 following spinal cord injury, TXB2 and 6-keto-PGF alpha
concentration and pathological changes in injured site 1, 2, 4, and 6 h after
injury were studied using a rabbit spinal cord injury model by Allen's weight
drop method.
PMID- 9639785
TI - Role of injury of gastric parietal vessels by immunocomplexes in the mechanism of
gastric mucosal lesion in portal hypertension with cirrhosis.
AB - The present experiment employed the immunohistochemical technique and
morphological observation to investigate the expression and distribution of C3,
C4, IgG, IgE 5-HT in portal hypertensive pigs with pathological change of gastric
mucosa and gastric parietal vessels. The wall of gastric mucosal mirco-vessels in
portal hypertensive pigs had a positive or strong positive reaction of C3, C4,
IgG, IgE and 5-HT with obvious injury of gastric mucosa normal pigs imparted
negative or feeble positive reaction, suggesting that during portal hypertension,
the gastric mucosal micro-vessels has deposit of immunocomplexes resulting in the
injury of the micro-vessels. It might be a factor involved in the pathogenesis of
the gastric mucosal lesion during portal hypertension with cirrhosis.
PMID- 9639786
TI - Application of color Doppler ultrasonic examination in deep vein valvular
incompetence in lower limbs.
AB - By use of color Doppler Flow Imaging (CDFI), the morphologic and hemodynamic
parameters such as the diameters of femoral and popliteal veins, blood flow
velocity and the reflux of valve area were examined in lower extremity deep
valvular incompetence (DVI) and normal control groups. The purpose was to
evaluate the value of CDFI in the diagnosis of DVI. The results demonstrated that
the parameters between the two groups had a very significant difference (P <
0.001), indicating that the CDFI is non-invasive, cost-effective and safe and it
might serve as a practical tool in the diagnosis of lower extremity deep valvular
incompetence.
PMID- 9639787
TI - Multiple respiratory gas monitoring causes changes of inspired oxygen
concentration in closed anesthesia system.
AB - Effect of multiple respiratory gas monitoring (MRGM) on inspired concentration of
oxygen in circuit system during closed anesthesia was studied in 51 adult
patients scheduled for abdominal surgery. Required flow rate of fresh oxygen
(OFR), inspired oxygen concentration (FiO2) and oxygen saturation of pulse
oximeter (SpO2) were measured continuously. Patients were equally divided into
three groups at random, group C (no MRGN used), group M1 (using MRGM with its
tail gas returned to circuit system), group M2 (using MRGM without tail gas
returned). The results revealed that during 180 min of closed anesthesia, OFR
required in group C and M1 were about 200-230 ml/min, and in group M2 it was
about 400 ml/min. In group C FiO2 decreased by about 10% after 60 min of closed
anesthesia (P < 0.01, 60 min vs 0 min) and then stayed stable at this level. In
group M1, FiO2 decreased by 16% at 60 min and 34% at 180 min and the decrease was
significantly greater than that in group C (P < 0.01). In group M2, FiO2 remained
constant during closed anesthesia, which was much higher than those in group C
and M1. The tail gas of Capnomac Ultima MRGM contained less oxygen than its
sample gas drawn from circuit system simultaneously.
PMID- 9639788
TI - Innervation of cholinergic vestibular efferent system in vestibular periphery of
rats.
AB - The innervation of cholinergic efferent fibers in the vestibular endorgans of the
rats was investigated using a modified preembedding immunostaining technique of
immunoelectron microscopy. A monoclonal antibody to choline acetyltransferase
(ChAT) was used as a marker of cholinergic fibers. It was found that there were
four types of cholinergic innervation in the vestibular endorgans of the rat: (1)
cholinergic nerve endings formed axo-dendritic synapses with afferent chalice
surrounding the type I sensory hair cells; (2) cholinergic nerve endings formed
axo-somatic synapses with type II hair cells; (3) cholinergic fibers synapse with
afferent nerve fibers and (4) a synaptic contact developed between cholinergic
nerve endings. The results demonstrated that a multiform innervation of the
cholinergic efferents exists in the rats vestibular periphery.
PMID- 9639789
TI - Development and application of an instrument for analysis of bone structure on
radiographs.
AB - An instrument used for quantitative assessment of trabecular structure of radius
on radiograph including trabecular number and trabecular width was developed
using a microdensitometer and a single-chip microcomputer. The device is
characterized by its high sensitivity, good reproducibility, convenience and
economy. The results obtained with the instrument were significantly correlated
to actual bone mineral content. This device can be used for the diagnosis of
osteoporosis, fluorosis, rickets and bone damages caused by cadmium.
PMID- 9639790
TI - Regulation of ApoE gene expression in mouse peritoneal macrophages by VLDL.
AB - Mouse peritoneal macrophages (MPM) were incubated with ApoE-poor VLDL or ApoE
rich VLDL at same concentrations for 24 h. The ApoE mRNA content increased in
both groups than that in control and the highest ApoE mRNA content was seen in
MPM incubated with ApoE-poor VLDL. The results suggest that VLDL could stimulate
ApoE gene expression in MPM and the ApoE-poor VLDL has more pronounced effect. We
think that the ApoE secreted by MPM may be incorporated into VLDL, especially the
ApoE-poor VLDL, and thereby enhance the uptake of those lipoproteins by MPM or
other local cells via ApoE-mediated receptor pathways.
PMID- 9639791
TI - Relationship between invasiveness of pituitary somatotrophinomas and structural
abnormalities of protein kinase C gene in human.
AB - The potential role of the protein kinase C (PKC) transduction system in
controlling proliferation of human pituitary somatotrophinomas was investigated.
Twenty somatotrophinomas were studied using PCR and direct sequencing methods. No
point mutation within the alpha PKC gene, previously thought to be associated
with invasive pituitary tumors, was found in any of the 20 somatotrophinomas. It
is concluded that PKC transduction system may play an important role in
controlling pituitary somatotrophinoma proliferation, but there is no correlation
between invasiveness and the previously reported alpha PKC gene mutation.
PMID- 9639792
TI - Induction of osteocalcin gene expression in vitro by progesterone.
AB - The effect of progesterone on osteocalcin gene expression was investigated in
order to understand how progesterone acts on osteoblast in vitro. For this
purpose, fetal rat calvarial osteoblasts were cultured in the medium containing
10(-9) M-10(-6) M progesterone respectively for two weeks while the cells
progressing differentiation. Northern blot analysis showed that progesterone
increased the level of osteocalcin mRNA in a dose-dependent manner. Among those
doses of progesterone employed in this study, only 10(-6) M hormone caused a
significant induction of osteocalcin gene expression (2.3 fold, P < 0.01). Our
results demonstrated for the first time that the osteocalcin gene expression is
regulated by progesterone. In addition, the results obtained from our study
provides a good evidence for the direct effect of progesterone on osteoblast in
vitro.
PMID- 9639793
TI - Abnormal change of p53 gene in gastric and precancerous lesions and APC gene
deletion in gastric carcinoma and near tissues.
AB - p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and
precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in
gastric carcinomas were studied by PCR/SSCP and PCR/RFLP. Results showed mutation
rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37.5% (3/8),
42.17% (8/19), 53.33 (16/30) respectively. There was significant difference among
groups of metaplasia, dysplasia, cancer and normal controls. No exon8 mutation
was found in metaplasia and dysplasia, but 4 cases were found to have exon8
mutation in cancer group. It is suggested that exon8 mutation occurs at the late
stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course of
precancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,
APC was 47, 37% (9/19), 8.73% (2/23), 16.67% (3/18) respectively. LOH of exon4
had something to do with poor differentiation, lymph node metastasis, depth of
invasion. LOH of exon4 may be of prognostic marker of gastric cancer. We are led
to conclude that p53 gene mutation is an early event and perhaps work together
with ras oncogene in gastric carcinogenesis.
PMID- 9639794
TI - The molecular epidemiological study on enteric adenovirus in stool specimens
collected from Wuhan area by using digoxigenin labeled DNA probes.
AB - A summer-autumn (1994) molecular epidemiological study of enteric adenoviruses
(EAds) in stool specimens collected in Wuhan area was conducted by using
Digoxigenin-labelled DNA probes specific to EAd40 and EAd41 respectively. 44 of
602 specimens were positive, among which 23 cases were identified as EAd40, 14
were EAd41 infection and 7 were dual infection. The ratio of males to females for
the positive specimens was 1. 44. The infection rate of EAd40 and EAd41 each
displayed no marked difference in seasons (summer and autumn) and similar age
distribution was found between them. All of the two types of EAds infections
predominated in patients with diarrhea under 3 years old. The results indicated
that the Digoxigenin probe could detect DNA quantities as low as 1 pg with
satisfactory specificity and the technique can be used for both clinical and
experimental purposes.
PMID- 9639795
TI - Preliminary studies on the relationship between autoantibodies to heat stress
proteins and heat injury of pilots during acute heat stress.
AB - Comparison in the heart rate, oral temperature and lymphocyte DNA damage during
heat stress was made in pilots with negative antibodies to heat stress proteins
(HSPs) and those with positive antibodies in the man-made climate room with
Western blot and comet assay. Our results showed that the increase in oral
temperature, heart rate and lymphocyte DNA damage in pilots with the positive
antibodies to HSPs were higher than those in pilots with the negative antibodies
during heat stress. These results indicated that the presence of autoantibodies
in plasma of pilots might reflect heat damage and high sensitivity to heat.
PMID- 9639796
TI - The study on the relationship between the expression of calponin and gallstone
formation.
AB - In order to understand the molecular mechanisms of gallstone formation, the
expression of calponin in animal model of gallstone disease was studied. High
cholesterol diet was given to the guinea pigs to induce gallstone formation. RT
PCR and Western-blotting were used to evaluate expression level of calponin gene.
Down-regulation of calponin gene expression was observed in animals with
gallstone, while myosin expression was relatively stable. Our results indicated
that the decrease of calponin could increase the pressure of Oddi's sphincter,
aggravate the stasis of bile and promote the gallstone formation.
PMID- 9639797
TI - The effect of levobunolol hydrochloride on the calcium and potassium channels in
isolated ventricular myocytes of guinea pig.
AB - The effects of levobunolol hydrochlorid (Bun) on the type L calcium channel
currents (ICA) and delayed rectifier potassium channel currents (IK) in isolated
ventricular myocytes of guinea pig were studied by using patch clamp whole cell
recording techniques. The results were showed that: 1) Bun caused a dose
dependent decrease in ICA and a dose-dependent increase in IK of the ventricular
myocytes. The threshold concentrations of Bun for ICA and IK were 10(-8) mol/L
and 10(-7) mol/L respectively. The maximum effective concentration of Bun for bot
ICA and IK was 3x10(-5) mol/L, and half-maximal concentration was 3x10(-6) mol/L;
2) IK was blocked by 2x100(-6) mol/L tetraethylammonium (TEA). A concentration of
3x10(-6) mol/L Bun showed a decreasing effect on the ICA as revealed by the
current-voltage relationship curve, i.e., Bun caused an elevation of the curve;3)
When ICA was blocked by 2x10(-6) mol/L Isoptin (Verapamil), at a concentration of
3x10(-6) mol/L Bun showed an increasing effect on IK and the effect could be
blocked by TEA. The above-mentioned results indicated that Bun had an inhibitory
effect on ICA and a fascilitatory effect on IK. The results suggested that the
molecular mechanisms of antihypertensive, heart rate slowing the beta -receptor
blocking effects of Bun might be due to decrease of ICA and increase of IK.
PMID- 9639798
TI - An experimental comparative study on the characteristics of ventricular
fibrillation during cardiac arrest and methoxamine administration.
AB - The effect of a pure alpha-adrenergic agent, methoxamine on ventricular
fibrillation (VF) amplitude and the relation between hemodynamic parameters and
survival in a rodent cardiopulmonary resuscitation (CPR) model were studied. Our
results suggested that: 1) VF amplitude decreased during untreated VF, but it
increased during pericardial chest compression: 2) methoxamine significantly
increased the mean aortic pressure (MAP) and coronary perfusion pressure (CPP)
but not VF amplitude, and the survival also increased due to elevation of CPP;
and 3) all surviving animals with successful defibrillation had a higher VF
amplitude.
PMID- 9639799
TI - Effect of left ventricular outflow on flow convergence region on the left septal
surface in ventricular septal defect.
AB - The corrected shunt flow rate (Fc) and corrected defect orifice area (Ac) were
calculated by modified equation F = 2 pi R2 (NL-VLVOT x Sin theta) in 23 patients
with single membranous ventricular septal defect, in order to correct the effect
of left ventricular outflow on flow convergence region on the left septal
surface. The results indicated that Fc was closely correlated with Qp-Qs, and
Qp/Qs measured by pulsed wave Doppler (r = 0.95 and r = 0.81 respectively, P <
0.001). And the correlation between Ac and the diameter of defect (Dd) measured
directly in two-dimensional views was better than that between uncorrected defect
orifice area (A) and the Dd (r = 0.98 and 0.69, respectively, P < 0.001). The
shunt flow rate calculated by ideal equation F = 2 pi R2 x NL overestimated the
actual shunt flow rate in ventricular septal defect, especially in membranous
type. Our study concluded that Fc can be used for a more accurate evaluation of
the shunt severity of ventricular septal defect.
PMID- 9639800
TI - A model of subarachnoid cavity drugs perfusion and its clinical application in
treatment of spinal cord injury.
AB - An animal model of subarachnoid cavity drugs perfusion and its prelimilary
clinical application in treatment of acute spinal cord injury (SCI) were
reported. Analysis of the heart rate (HR), ECG blood pressure (CVP, CAP)
cerebrospinal fluid (CSF) pressuer and CSF gas and pH values of 10 healthy adult
goats during subarachnoid daxamethasone verapamil perfusion showed that this
model was safe anti reliable. 26 patients with acute SCI were selected for a
clinical obseration. Good results were obtained in 7 cases who received this
treatment of subarachnoid cavity perfusion with dexamethasone and verapamil.
PMID- 9639801
TI - Sonographic diagnosis of bone tumors.
AB - This paper presents the results of sonographic and radiographic examinations in
48 patients clinically diagnosed as having bone tumors. Sonography revealed bone
destruction in all 48 cases, elevated periosteum in 26 cases and soft tissue mass
in 34 cases. The results obtained in this series demonstrate that most bone
tumors have their characteristic sonographic features such as giant cell tumors,
malignant bone tumors, bone cysts, as well as metastatic lesions. Study showed
that sonography has equally high accuracy in the diagnosis of these tumors
compared with radiography.
PMID- 9639802
TI - Color Doppler monitoring of changes of utero-placental-fetal circulation in
normal pregnancy and intrauterine growth retardation.
AB - The utero-placental-fetal circulation (UPFC) of 150 subjects during second and
third trimester was examined by using color Doppler. Of them 89 were normal woman
and 58 were patients with intrauterine growth retardation IUGR). Our results
showed that UPFC was increased gradually during normal pregnant period. In IUGR
patients it was revealed that TAV and Q of UmA, UmV and UtA decreased at 20th
week of gestation, especially after 30th week. PI, RI and S/D ratio of UmA were
increased, but TAV, Q of UmA and UmV were markly reduced, so was UtA. PI were
increased, but the changes of RI, S/D ratio in UtA were not significant.
Hemodynamical findings of UmA, UmV and UtA were abnormal in 92.53% of IUGR
patients. Only 81.03% present abnormal S/D ratio of UmA (P < 0.01) and the
difference was statistically significant. Maternal serum E3, HPL level in IUGR
were significantly lower than that of the normal. 6KP level was reduced, TXB2/6KP
ratio was significantly increased. TXB2/6KP ratio was markedly related with TAV,
Q of UmA, UmV and UtA. Our results suggested that using color doppler ultrasound
for examination of hemodynamical changes of UmA, UmV and UtA could revealed UPFC
function directly. It is one of the best methods for monitoring IUGR and might be
used for early diagnosis of IUGR. The main pathophysiological changes of IUGR
were UPFC obstruction and placental disfunction.
PMID- 9639803
TI - Effects of cyclosporin A on proliferation of cultured rat mesangial cells.
AB - The proliferation of mesangial cells on cyclosporin (CsA) test medium was studied
by MTT assay and TNF-alpha in cultured supernatant was examined by using ELISA.
The results showed that cyclosporin A significantly inhibited the proliferation
of mesangial cells at the concentration between 0.25-15 micrograms/ml (IC50 1
microgram). This action appeared to be dose-dependent. Release of TNF-alpha from
mesangial cells stimulated by LPS was also dose-dependently suppressed. It is
suggested that cyclosporin A play an important role in antiproliferation
mechanism of mesangial cells in vitro.
PMID- 9639804
TI - Tissue response and the cytoconduction ability to collagen/hydroxyapatite
heterotopic implantation.
AB - A histological and ultrastructural observation of CHA implanted intramuscularly
and subcutaneously had been reported. Our results showed that a mild inflammation
developed at the early stage and disappeared 2 weeks after implantation. The
infiltrating cells were mainly monocyte-macrophages, a number of fibroblasts
followed macrophages closely. It was possible that as CHA degrades, monocyte
macrophages continuously released inflammatory factors, thus enhancing fibroblast
proliferation activity and tissue regeneration. In addition, the heterotopic
calcification of collagen matrix was observed, suggesting that CHA promoted
calcification deposition.
PMID- 9639805
TI - The factors related to fungal peritonitis in patients on peritoneal dialysis.
AB - Fungal peritonitis (FP) is a serious infectious complication of peritoneal
dialysis (PD). This retrospective study was conducted in 11 cases of FP among 64
cases of patients with bacterial peritonitis (BP). Our results showed that age
and sex underlying disease did not correlate significantly with the development
of FP (P > 0.05), while long-term, repeated administration of antibiotics did (P
< 0.01). It is suggested that the patients recently suffering from BP and being
resistant to antibiotics were at great risk of suffering from FP. The key to
prevent FP was to avoid BP, to use sensitive antibiotics with appropriate courses
and to give nutritive treatment.
PMID- 9639806
TI - Lipids, lipoproteins and apolipoproteins abnormalities in patients undergoing
dialysis.
AB - Twenty hemodialysis (HD) patients and 20 patients on continuous ambulatory
peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins and
apolipoproteins abnormalities. HD patients had elevated serum triglyceride,
decreased high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I
(Apo A-I), while CAPD patients had elevated total cholesterol, triglyceride, low
density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-I
ratio, and decreased HDL-C, Apo A-I. Because of the molecular sieving effects of
peritoneum, CAPD have a negative effect on these abnormalities. CAPD patients
might be at greater risk of developing coronary artery disease than HD patients
who are also at increased risk as compared with normals.
PMID- 9639807
TI - [Co-regulative effect of PKA-RII and PKC-alpha kinase subspecies on expression of
c-myc and c-H-ras in human gastric cancer cells (MGC 80-3)].
AB - Based on preceding experiment, we further studied the co-regulative effects of
PKA-R II and PKC-alpha on expression of oncogenes in human gastric cell line MGC
80-3. The c-myc and c-H-ras expression were suppressed in MGC 80-3 cells during
HMBA-induced differentiation. At the same time, PKA-R II showed nuclear
translocation from cytoplasm, whereas the expression of PKC-alpha shifted from
nucleus to cytoplasm. PKA inhibitor (Sigma) was added to block cAMP-PKA pathway
when cell differentiation were induced by HMBA. The PKA-R II was still located in
cytoplasm but expression of PKC-alpha translocated again into nucleus. Meanwhile,
the c-myc and c-H-ras again expressed. This suggested that the changing
regulation of oncogene expression were closely related to signalling from nuclear
translocation of kinase subspecies. It thus shows the co-regulation effects of
two signal system on oncogenes expression.
PMID- 9639808
TI - [Internalization of tumor associated antigen on human lung adenocarcinoma cell
line SPC-A-1 by McAb LC-1].
AB - Antigenic modulation of tumor cells is a kind of immunophenomenon that the
antigenicity of tumor cell surface antigen could be lessened, weakened or
completely lost. It is a potential route for tumor cells to escape the
immunosurveillance and immunoattack of the host. One of the means to cause the
antigenic modulation is by means of the antibody. In present research, gold
labeled monoclonal antibody LC-1, which is raised against human lung cancer in
our lab, as a molecular tracer to study the internalization and the subsequent
fate of the membrane tumor associated antigen-LC-1 complex on the SPC-A-1 cell
surface has been used. We found that this complex was internalized via the
receptor-mediated endocytic pathway and concentrated in the multivesicular bodies
and transported to lysosomes for proteolysis in the end. Strikingly, we noted
that LC-1 had induced the autophagocytosis of ribosomes in SPC-A-1 cells in the
median time it induced the internalization of the cell surface antigen cause by
internalization and the restoration after antigenic modulation were also analyzed
by the fluorescence activated cell sorter (FACS).
PMID- 9639809
TI - [Apoptosis of HL-60 cells induced by Harringtonine: membrane blebs, nucleus blebs
and chromatin condensation].
AB - Using Video Enhancement Contrast (VEC) microscopy, we recorded the morphological
changes of same HL-60 cell in the processes of apoptosis induced by
harringtonine. Our results show that all of apoptotic cells need several nucleus
blebs before their chromatin condensation. Every nucleus bleb is induced by a
relative membrane bleb. The number of membrane blebs is much higher than that of
nucleus blebs, so there are only some of membrane blebs which can induce nucleus
blebs. It suggested that membrane and nucleus blebs probably are related to
apoptotic chromatin condensation. After HL-60 cells pretreated with cytochalasin
B(CB), apoptotic chromatin condensation delayed eight hours, but no membrane
bleb, nucleus bleb and apoptotic body formed eventually. So membrane and nucleus
blebs during apoptosis are related to microfilament re-organization and can
accelerate apoptotic chromatin condensation, but are unnecessary for apoptotic
chromatin condensation. All this suggested that nuclear changes and cytoplasmic
changes during HL-60 cell apoptosis are independent.
PMID- 9639810
TI - [Study on the transferring of YACs to new host by means of KAR cross].
AB - The donor yeast strain YAC23 containing a 340 kb human genomic DNA fragment in
YAC (Yeast Artificial Chromosome) was mated with recipient strain YLB504 by means
of improved kar cross and the condidate YACductants were assayed by PCR and the
amplification band of 404 bp indicated that they were the same as those of
recipient strains (i.e. MAT alpha). Further analysis of the electrokaryotype of
the candidate YACductants by PFGE (Pulsed Field Gel Electrophoresis) confirmed
that the YACs had succeeded in entering into the recipient cells. The YACs had
thus completed the process of transferring from one host to the other.
PMID- 9639811
TI - [Cell-free nuclear assembly induced by nucleoli and demembranated macronuclei
from Tetrahymena shanghaiensis].
AB - Nuclei assembled in Xenopus egg extracts from exogenous DNA or chromatin are
morphologically similar to normal eukaryotic nuclei except that they do not
contain nucleolus-like structure. Previous work show that prenucleolar bodies
could be found in these nuclei, but they are unable to fuse with each other,
probably due to the absence of a functional nucleolus organizer. It is
interesting to know if exogenous functional nuclei could act as functional
nucleolus organizer to induce the formation of mature nucleoli. To test this
possibility, nucleoli and demembranated macronuclei which contain perinuclear
distributed nucleoli were isolated and purified from Tetrahymena shanghaiensis
and were introduced into Xenopus cell-free system. By EM observation, we showed
that these nucleoli, both individual isolated and perinuclear distributed, could
not keep their original morphological characteristic, but undergo a series of
structural changes resembling nuclear assembly induced by exogenous chromatin. No
nucleolus-like structure was found in these nuclear like structure. These results
indicate that functional nucleolus organizers could neither keep their original
activity of RNA transcription nor induce the formation of new nucleoli in Xenopus
egg extracts.
PMID- 9639812
TI - [A novel conservative structure found in the carp mitochondrial tRNA(phe) gene].
AB - A nucleotide sequence for the tRNA(phe) gene of Carp mitochondria was determined.
Sequence data comparisons made among the whale, human, Xenopus laevis, bovine,
mouse, chicken and carp, showed that a novel conservative structure was found in
the D. stem (dihydrouridine stem), which was known had variant nucleotides in any
other vertebrate mitochondrial tRNA and cytoplasmic tRNA genes. This conservative
structures contains 13 bp. When we compared the front 7 bp of the conservative
structure with the eukaryotic RNA Pol III recognitive A domain, we found these
two kinds of different species had partly homologue. As the mitochondrial
tRNA(phe) gene is located between the displacement loop and mitochondrial rRNA
gene, we inferred that the novel conservative structure might have some extra
interesting functions.
PMID- 9639813
TI - [The mechanism of vasculogenesis: the critical role of transforming growth factor
beta 1 in the formation of vessel-like structures during the differentiation in
vitro of murine embryonic stem cells].
AB - When ES-5 cells were transfected with an exogenous porcine TGF-beta 1 gene, one
can obtain clones of genetically modified ES cells with over-expression of the
transfected gene. We called the genetically modified ES-5 cells as ES-T cells.
When ES-T cells were used to study their differentiation in vitro by all trans
retinoic acid (RA), it was soon noticed that embryoid bodies of ES-T cells can
exclusively differentiate into endothelial cells and vessel-like structures, but
not in their parent ES-5 cells. The above result is the first indication that the
differentiation of tubular structures in embryoid bodies of ES-T cells may
somehow be related to TGF-beta 1. To demonstrate further the role of TGF-beta 1
in the formation of vessel-like structures, the cultured ES-5 cells in the
presence of added rhTGF-beta 1 were closely followed in the course of their
differentiation. We have, thus, demonstrated the promoting effects of exogenous
rhTGF-beta 1 in the formation of vessel-like structures, morphologically similar
to those structures derived from ES-T6 cells, during the differentiation of ES-5
cells, both in monolayer culture, in three dimensional collagen gel and in
embryoid bodies cultured on gelatin-coated tissue culture wells. Addition of
suitable amount of anti-TGF-beta 1 monoclonal antibody IgG (TB21) to the culture
medium of embryoid bodies of ES-T6 cells could effectively abolish the formation
of vessel-like structures induced by retinoic acid. The percentage of the
inhibition was very high, giving a figure comparable to that of atypical vessel
like structures formed in the control embryoid bodies from their parent ES-5
cells. The flat epithelial-like cells and round cells differentiated from
embryoid bodies of ES-T6 cells were stained rather strongly for laminin and type
IV collagen by immunofluorescent procedure. The above results indicate clearly
that TGF-beta 1 is a crucial factor in organizing the differentiated derivatives
(endothelial-like cells and their immediate progenitor cells) from ES-T6 cells to
form vessel-like structures, and that the role of TGF-beta 1 in vasculogenesis
might be performed, in part, through the modulation of the composition and
organization of the extracellular matrix. In addition, the enhanced expression of
bFGF mRNA in derivatives differentiated from both ES-5 cells treated with rhTGF
beta 1 and ES-T6 cells were detected by Northern blot analysis. Thus, aside from
its effects on extracellular matrix, TGF-beta 1 might also modulate the
bioactivity of bFGF in relation to the growth of vascular endothelial cells in
the present system.
PMID- 9639814
TI - [Cloning and screening on tumor-related genes inactivated in rat hepatoma cells.
II. Reversion of malignant phenotype of hepatoma cells].
AB - A rat normal expressing cDNA library was established and subsequently its whole
DNA was transfected into CBRH-7919 rat hepatoma cell cultures. With neomycin
selection and morphological distinction, several reversed colonies were isolated
and subcloned. All these colonies showed decreased growth rates, reduced capacity
for foci formation on soft agar and tumorigenicity in nude mice compared to CBRH
7919. Analysis of rescued plasmid cDNA from these colonies is under way.
PMID- 9639815
TI - [A retrotransposon-like element Tca1 was used for taxonomic determination of
Candida albicans].
AB - We had isolated from Candida albicans a moderately repetitive sequence designated
alpha and a retrovirus-like transposable element Tcal (Transposon Candida
albicans). The Tcal consisted of two 388bp direct repeats of the alpha element,
called LTR (Long Termination Repeat), which was separated by approximately 5.5kb
of DNA. A large number of strains from America and China have been grouped based
on patterns of hybridization bands visualized on Southern blots of EcoRI digested
genomic DNA probed with alpha and Tcal element internal sequence. Strains from
same area have higher relatedness than those from different area. The
hybridization patterns with URA3 and other DNA probes were also conserved within
the groups. alpha element are species specific, no hybridization was observed
with genomic DNA of other yeast species. The data presented here indicate that
the alpha element can be employed to distinguish between species and to assess
strain relatedness within C. albicans, we suggest that Tcal may be relevant to
the genomic evolutions of C. albicans and the pathogenic potential of the
organism.
PMID- 9639816
TI - Essential region for self-replication of Coryneform bacteria plasmid pXZ10145.
AB - A pTSK series of recombinant plasmids were constructed by cloning DNA fragments
of pXZ10145 or its deleted deriviate pATN65 into plasmid vector pACYC177 of E.
coli. Experiment results of Coryneform bacteria transformation with these pTSK
plasmids allowed us to localize the essential region for self-replication on
plasmid pXZ10145. The minimal replication region of the pXZ10145 was located on a
1.2kb Nael-Nrul DNA fragment in which only one open reading frame was found. This
ORF was believed to be encoded a trans-acting replication factor. The replication
origin (oriV) was locate on a 0.3kb NaeI-SalI fragment which was within the ORF
region.
PMID- 9639817
TI - Cloning and expression of full-length delta-endotoxin cryIA(c) gene in three
kinds of prokaryotic systems using shuttle vector pHT3101.
AB - Two fragments, 6.5kb and 4.3kb encoding 5' end and 3' end of delta-endotoxin
cryIA(c) gene, respectively, were selected from the Bacillus thuringiensis
kurstaki-HD-73 75kb plasmid gene pool using random primer labelling delta
endotoxin cryIA(b) gene probe. The full-length 3.92kb cryIA(c) gene including 5'
end 152 bp promoter sequence and 3' end 198 bp terminater sequence was rebuilt
after uncoding sequences were deleted. Three kinds of engineering strains
harbouring the same recombinant plasmid pHTY1 were obtained after the cryIA(c)
gene had been subcloned in shuttle vector pHT3101 and transformed to E. coli
NM522, Bacillus subtilis AS1176 and Bacillus thuringiensis crystal-deficient
4D10(H3ab). SDS-PAGE electrophoresis patterns reveal that the cryIA(c) gene
expressed the same 133,300 protoxin proteins in all three host systems with the
same molecular weight to the crystal protein from the Bacillus thuringiensis
kurstaki HD-73. Immuno-assays indicate that the expression proteins can react
with antiserum of HD-73 paraspore crystal protein in the same pattern as the
natural crystalprotein. Bioassays using crude expressed products from three host
strains reveal that they all showed toxicities to second instar larvae of
Plutella xylostella, and their LD50 were calculated to be 0.311 micrograms/cm2,
0.02 micrograms/cm2 and 0.017 micrograms/cm2, respectively.
PMID- 9639818
TI - [Immunogenicity of recombinant S. typhimurium ex. pressing a hybrid antigen of
Plasmodium falciparum].
AB - We have expressed a 74-peptide hybrid Plasmodium falciparum antigen as fusion
protein in attenuated Salmonella typhimurium SL3261. Live organisms were orally
immunized Rabbits with a dose of 2 x 10(9)cfu. Specific anti-serum were detected
by ELISA after immunization. Obvious Delayed type hypersensitivity (DTH) could be
induced by PfAg and GZ-C antigen. The recombinant vaccine had no evident side
effects to the hosts. Our studies indicate that attenuated Salmonella typhimurium
SL3261 can express synthetic P. falciparum antigen with several epitopes and live
organisms can activate special cell-mediated immunity and humoral immunity.
PMID- 9639819
TI - [Studies on midecamycin 4"-O-propionyltransferase gene structure].
AB - A BamHI-BamHI 8.0 kb DNA fragment which contains midecamycin propionyltransferase
(mpt) gene was digested with different restriction enzymes and the restriction
map was made. The mpt gene was localized in a EcoRI-EcoRI-PstI3.0 kb DNA fragment
by Southern blot analysis using a 2.4 kb DNA fragment of the CarE gene as a
probe. The 3.0 kb DNA fragment of mpt gene was cloned into E. coli/Streptomyces
shuttle vector pWHM3 and a recombinant plasmid pWFPE was obtained. S.
ambofaciens(pWFPE) and S. lividans(pWFPE) can convert endogenously synthesized or
exogenously added spiramycin into 4"-O-propionylspiramycin, respectively.
Sequence analysis of mpt gene demonstrated an open reading frame in the EcoRI
EcoRI-PstI3.0 kb DNA fragment, which starts with ATG and ends with TGA. Mpt gene
encodes a product of 388 aa. G+C mol% of mpt is 68.0 and G+C mol% of 3rd codon
position is 91.5. The putative product of mpt has a identity of 67.6% and a
similarity of 86.4% with CarE product. A consensus RBS GAGGT in the 6bp upstream
from ATG and a promoter region were found. An inverted repeat sequence in the
downstream from TGA acts as transcriptional terminator.
PMID- 9639820
TI - [A legionella pneumophila strain serologically cross-reacting with thirteen
serogroups of this species].
AB - A bacterial strain, designated as Jin-1, was isolated from a water sample taken
from the Jinyang Lake located in the suburbs of Taiyuan City, Shanxi Province.
Its morphologic and tinctorial properties, nutritional requirements, growth
characteristics, biochemical reactions, as well as results of DNA and peptide
analysis overall met the criteria for identification of Legionella pneumophila.
In serogrouping, extensive cross-reactions between Jin-1 and the type strains of
L. pneumophila serogroup 1 through 14 were observed in both slide and tube
agglutination tests mediated by the IgM antibodies. However, Jin-1 revealed the
L. pneumophila serogroup 5 specificity in IFA, ELISA and dot-ELISA, all mediated
by the IgG antibodies. Jin-1 was finally identified as a strain of L. pneumophila
serogroup 5 with the more complex antigenic composition than the ATCC type strain
of this serogroup. The taxonomic conclusion has been confirmed by CDC. A
Legionella pneumophila strain which serologically cross-reacting with so many
serogroups of this species has never been reported in the published articles. It
is presumed that the cross-reacting antigen of Jin-1 belongs to the thymus
independent antigen by nature.
PMID- 9639821
TI - [Studies on some characteristics of a strain of mink infectious enteritis virus].
AB - A strain of mink infectious enteritis virus that was isolated from the east
district of China can be bred on FK cell. Concentrated viruses were purified by
using Sepharose-4B chromatography. The size of the virus was about 20-22 nm by
electron microscope. Viral nucleic acid was extracted from pure virus by using
SDS-protease K-Phenol. Tests with diphenylamine, acridine orange and the curve of
thermal dentuation, etc. showed that the virus had a single-stranded DNA. The
molecular weight of the ssDNA was from 1.5 x 10(6) to 2.0 x 10(6) determined by
length of the virul nucleic acid.
PMID- 9639822
TI - [Microcolony observation for rapid detection and identification of cultures of
Mycobacterium tuberculosis].
AB - 219 sputa were seeded on Kuang's agar plates. A total of 112 isolates of
Mycobacterium tuberculosis were detected in 219 specimens. Of these 112 isolates,
104 (92.8%) were detected in Kuang's agar media and 108 (96.4%) were detected by
microcolony observation. The detection time of microcolony observation and
culture method needed 11 and 18.6 days respectively. The detection time of
microcolony method is much shorter (P < 0.001). The results of conventional tests
of different species of Mycobacterium and microcolony differentiation were
identical in 99% of isolates of Mycobacterium tuberculosis.
PMID- 9639823
TI - [Studies on modulation and control sigma 38 and RMF for the expression of some
genes].
AB - The E. coli mutants and wild type strains of rpoS and rmf were cultured in rich
medium LB and limited component medium EP respectively. During the stationary
phase, the viable cells of mutants were less than wild type strains's. The change
of the product of serial proteins was quantified with Western blot. Sigma 38 has
not effects on the product of rpoA, rpoB, rpoC, groE and tu gene, depress the
transcription of crp and promote the expression of rmf. RMF can promote
expression of rpoA, rpoD, groEl, rho, ompA and tufA gene in rich medium, but not
in limited medium, and then depress and promote the expression of crp and rpoS
respectively.
PMID- 9639824
TI - [A new zoonosis--investigation of Gardnerella vaginalis disease of fox. V.
Studies serotype of Gardnerella vaginalis in fox].
AB - 145 strains Gardnerella vaginalis isolated in foxes were isolated from 13 main
farms raising foxes in six provinces (regions), China, after antigenicity and
immunogenicity of the strains were measured, 1-3 appropriate strains were
selected from each farm raising foxes for serotype studies. Cross agglutinin
absorption test confirmed that selected 26 strains Gardnerella vaginalis were
divided into three serotypes and then the representing strains were used to
produce typing serum. Among remaining 119 strain, 108 strains were typable with
the typing sera, and 11 strains can't be set. Among three serotypes, serotype I
made up 79.1% of the strains. It was shown that serotype I was the principal
serotype of Gardnerella vaginalis of fox in China. The test also confirmed that 5
strains of Gardnerella vaginalis isolated from racoon dog, 4 strain Gardnerella
vaginalis from mink and 2 strains Gardnerella vaginalis from canine also belonged
to serotype I. Supersonic antigben was produced with three serotypes,
representative strains. By agar immuno-diffusion test, it confirmed that the
antigens of three serotypes formed a obvious blending precipitating line with the
homologous or heterologous serotype antiserum. It indicated common antigen
existed among all serotypes. The agar immuno-diffusion test results revealed that
the precipitating line of the homologous serotype completely blended. It is our
opinion that the method of serotyping is reliable.
PMID- 9639825
TI - [Analysis of surface antigen molecule expression on serovar stains of Neisseria
gonorrhoeae by flow cytometry].
AB - In the present experiment, flow cytometry was employed for analysing expression
characteristics of the antigen molecules distingushed by 10 monoclonal antibodies
against Neisseria gonorrhoeae lipooligosaccharides. Stability of antigen
expression and amount of epitope on the surface of N. gonorrhoeae were
quantitative determined. Reactivity of the monoclonal antibodies with serovar
strains of N. gonorrhoeae were evaluated.
PMID- 9639826
TI - [Study of relationship between the bacteria in air and the clinic infection].
AB - The Source of infectious bacteria is the first problem in provension of infection
considered by the medical workers. In this paper, with the method of bacteria
plasmid analysis, chromosome DNA restriction fragment length polymorphism
analysis, drug resistance experiment (antibacterial drug, sterilizing drug) and
so on. We confirmed that staphylococci of nosocomi is mainly from air; but the
gram-negative bacteria is mainly from the patient's pharyngeal portion; and cause
hospital infection indirectly. The drug resistance of gram-negative from air was
lower than the same gram-negative bacilli's isolated from the patient. Moreover,
kill bacteria the infectious strain is same strain in air. Above-mentioed results
provided the important basis for control of the hoslpital infection.
PMID- 9639827
TI - [Regulation of purine biosynthetic genes expression in Salmonella typhimurium. V.
Nucleotide sequences evidence without purJ gene].
AB - Previous genetic analysis showed that AICAI transformylase, IMP cyclohydrolase
and GAR synthetase are encoded by purJ, purH and purD respectively, and which
constitute a operon, mapped on 90 min in genetic map of Salmonella typhimurium
But recent study in E. coli indicated that the genes encoding for above three
enzymes only have purH and purD, without purJ gene. Report here is the DNA
sequences evidence for abence of purJ gene in Salmonella typhimurium.
PMID- 9639828
TI - [Cloning and identification of fliCi gene of Salmonella typhimurium].
AB - Purified Salmonella typhimurium 8705 chromosomal DNA was digested with EcoRI. DNA
fragments above 400 bp were obtained by Sepharcyl S-400 chromatography and cloned
into vector pGEM-3Zf(-), then transformed into host cell LC2a (hag- is recA-).
One out of 6013 transformants was found to be motile and this clone was named
pGI4015. Miniprep proved that pGI4015 contained an inserted fragment about 15.3
kb. Motility/inhibition tests as well as Southern blot hybridization showed that
pGI4015 bear the H-1i gene of S. typhimurium. With the aid of BamHI and SalI
site, sequences unrelated to flagellin in the cloned DNA fragment was removed,
and a 3.8kb fragment containing fliC gene was subcloned.
PMID- 9639829
TI - [Studies on purification and some properties of nisin from Lactococcus lactis
subsp. lactis Al2].
AB - Nisin from Lactococcus lactis subsp. lactis AL2 was extracted with n-propanol
from NaCl-saturated culture and purified by ion-exchange chromotography on CM
Sephadex C-25. Nisin was purified 1.63 fold with a yield of 41.7%. The molecular
weight of nisin was determined by SDS-PAGE to be about 3500. Nisin activity was
stable at low pH and sensitive to digestion by a-chymotrypsin. Nisin is capable
of inhibiting a broad range of gram-positive bacteria. In contrast, the gram
negative bacteria, yeasts, molds and Nip+ L. lactis subsp. lactis ATCC11454 were
not inhibited.
PMID- 9639830
TI - [An experimental animal model study of HCMV].
AB - This Paper is a study of animal model on the Kunmin and BALB/C mice infected HCMV
AD169. The death-rate showed a marked higher BALB/C mice (28.75%) than the kunmin
mice. The Kunmin mice Percentage of diseased (94.74%) higher than BALB/C mice.
Brian tissue of two groups mice that pathological changed was equal by HCMV
infected.
PMID- 9639831
TI - [Distribution of Bacillus thuringiensis in soils of north and south of China].
AB - 221 isolates of Bacillus thuringiensis were isolated in 1491 soil samples from
North and South of China. H-serotypes and larvicidal characters of all Bt
isolates have been identified. The rate of Bt-harbouring soil sample and the rate
of Bt isolates in Northeast and Neimeng were in 12.6% and 17.2% respectively.
Predominant serotypes were H4, H10, H3, H13, H5 and H29. The most fertile Bt
harbouring area was the Heilongjiang Province with rate of Bt-harbouring sample
of 21.4% and rate of Bt isolate of 29.4%. Rate of Bt-harbouring sample and rate
of Bt isolate in Northwest area were 6.6% and 7.1% respectively. Main serotypes
were H4, H5, H19, H10 and H3. In four provinces of Southern China, both rates
above were 18.6% and 29.5%, but frequency of Bt distribution was varied seriously
in different distinct. Predominant serotypes in soils from Southern China were H3
and H5. Results of bioassay showed that the percentage of strains high active to
Heliothis armigera and Plogioidera versicolora were 1.6% and 1.1% in soils from
North of China. In contrast to North of China, Bt strains active to H. armigera
were 5.3% and none of Bt was effective to P. versicolora in South of China. A
strain H27-05 was high toxic to H. armigera and showed temperate toxicity to P.
versicolora.
PMID- 9639832
TI - [Characterization of insecticidal crystal proteins of Bacillus thuringiensis
subsp. chinensis CT-43].
AB - Bacillus thuringiensis subsp. chinensis CT-43, no flagellum, produces various
shaped parasporal crystals, which consist of 140000, 130000, and 65000 proteins.
Based on two kinds of mutant, 140000 and 130000 crystal protein individually
forms bipyramidal crystal and the 65000 protein forms cubidal crystal, and that
the 140000 and 130000 protein is activated by trypsin into 55000 and 66000
proteins and 60000 protein, respectively. Bioassay were conducted to 3rd instar
Plutella xylostella larvae with crystals, soluble crystal proteins, and activated
crystal proteins, respectively, and it indicated that high toxic mutants can be
obtained by curing low toxic crystal genes, and that the toxicity of crystals can
be improved 16.3 to 58.4 times after solubilization.
PMID- 9639833
TI - [Preliminary research on Bifidobacterium cuniculi in stomach and intestines of
rabbits].
AB - The distribution of Bifidobacterium in stomach and intestines of ten healthy
rabbits were studied by microecological methods. The results showed that
Bifidobacterium exist in stomach, small intestine and large intestine, the amount
hightest in large intestine, second in jejunum and no finnd in duodenum. Being
isolated, purified and biologically identified, the bacteria was identified as
Bifidobacterium cuniculi, whose other biological characteristics also was
studied.
PMID- 9639834
TI - A population-based study of lens opactities.
AB - PURPOSE: Age-related lens opacity is the main cause of vision disability in
elderly population all over the world. This study was designed to investigate the
prevalence and incidence of lens opacity. METHODS: 1817 eyes of 932 adults over
45 years-old were sampled randomly from 4 villeges within Doumen, a county
located in the south of Guangdong provience, China. The procedure of the
examination was performed by ophthalmologists. The lens opacities were graded
according to a standarized photo of the Lens Opacities Classification System II
(LOCS-II). RESULTS: The prevalence of lens opacities in nuclear color, nuclear
opacity, cortical opacity and subcapsular opacity was 16.1%, 28.6%, 30.3% and
8.7%, respectively. The frequency of all four types of opacities increased with
age. The prevalence of lens opacities in four types was higher in female than
that in male. CONCLUSION: The data we got are important for prevalence of lens
opacities of population-based study as well as basic information for cohort study
in the future.
PMID- 9639835
TI - The etiology of vision impairment in target population.
AB - PURPOSE: research the etiology of vision impairment in target persons over 45
years old in Doumen county, Guangdong province. METHODS: Depending on the
prevalences of the blindness among the person aged over 50 years, the theoretic
sample rate is 1,000/4,8733 x 100% = 2.05%. The 8 districts were divided into 3
parts according to the local economic situation and the proportion of the
population in the areas. In fact, the sampling rate is 932/10055 = 88.34%.
RESULTS: We found that impairment < 0.3 accounted for 10.94%. The prevalence of
bilateral blindness and low vision was 1.61% and 3.22%, respectively. Both
prevalences of blindness and low vision were increased with age. The leading
cuase of blindness was cataract (45.2%). The second was corneal opacity (16.7%).
Prevalences of the low vision and the blindness were higher in females than in
males (P < 0.005). CONCLUSIONS: Curable and preventable diseases were the leading
cause for the blindness (70%). Prevalences of blindness and the low vision
increase with age. We will continually follow up the population over 50 years of
age in Doumen county.
PMID- 9639836
TI - Relationship between myopia and optical components--a study among Chinese Hong
Kong student population.
AB - PURPOSE: To establish the prevalence and severity of myopia among the Chinese
Hong Kong students and to study the relationship between myopia and optical
components. METHODS: One thousand and seventy-five freshmen of the 1993-1994
academic year in the Chinese University of Hong Kong underwent the eye
examination including evaluation of refractive error, keratometry, and A-scan
ultrasonic biometry. The data were analyzed with the SPSS/PC+4.01 statistical
package. RESULTS: The prevalence of myopia was 91.7% with the mean refraction
being -4.00 +/- 2.64D in this young adult population. The statistical analyses
demonstrated a significant correlation between refractive value and axial length
of the globe (r = -0.78), vitreous length (r = -0.76), anterior chamber depth (r
= -0.33), lens thickness (r = 0.13) and corneal curvature (r = 0.19). CONCLUSION:
The refractive status is mainly dependent on the axial length. In general, the
higher the myopia was, the longer the eyeball, the deeper the anterior chamber,
the steeper the cornea, and the thinner the lens would be.
PMID- 9639837
TI - A dynamic and quantitative study of pattern visual evoked potentials and gamma
aminobutyric acid neurones in the lateral geniculate nucleus and the visual
cortex of monocular deprivation cats.
AB - PURPOSE: To assess the effects of monocular lid closure during critical period on
cortical activity. METHOD: Pattern visual evoked potentials (PVEP) of the normal
and the monocular deprivation (MD) cats were dynamically measured and the number
of gammaaminobutyric acid immunopositive (GABA-IP) neurones of the area 17 of the
visual cortex and the lateral geniculate nucleus (LGN) was quantitatively
compared by using immunohistochemical method (ABC). RESULTS: The amplitude of the
N1-P1 attenuated in deprived eyes (DE), NE/DE at postnatal week (PNW) 7-8 (P <
0.05), NE/DE at PNW 15-16 (P < 0.01); while P1 latency delayed, NE/DE at PNW 7-8
(P > 0.05), NE/DE at PNW 15-16 (P< 0.05). The numbers of GABA-IP neurones in
layer A1 of the ipsilateral LGN and in layer A of the contralateral LGN, compared
to those in the corresponding normal laminae, were not significant at PNW 7-8 and
PNW 11-12 (P > 0.05), while in the same cats a reduction in the number of GABA-IP
neurones was found in layer IV of area 17 at PNW 11-12 (P < 0.05). However, with
longer survival of 3-4 weeks in duration, the numbers of GABA-IP neurones in the
deprived laminae of LGN were remarkably reduced (P < 0.05). CONCLUSIONS: The
amplitude of N1-P1 components is sensitive to the effects of monocular
deprivation. Monocular deprivation in cats during critical period leads to
dramatic changes of the number of GABA-IP neurones in the LGN and cortical layer
IV receiving inputs from the deprived eye in cats. The deprivation-induced
reduction in GABA-IP neurones is delayed in the LGN compared with the visual
cortex. PVEP of the MD cats is consistent with the damage of its GABA system in
visual cortex.
PMID- 9639838
TI - The visual deprivation and increase in axial length in patients with cataracts.
AB - PURPOSE: To investigate the relationship between axial myopia and visual
deprivation in patients with cataracts in their youth. METHODS: Forty myopic eyes
of 25 cases had long deprivation of form vision due to cataracts during their
youth. The axial length was measured by A-Scan ultrasound. RESULTS: The axial
length is 2-6mm (mean: 3.7mm) longer than the other eyes in 10 patients with
unilateral cataracts. Fifteen cases with bilateral cataracts had 25-29mm of axial
length (mean of the right eyes 26.8mm and the left eyes: 26.7mm). Six cases with
unilateral cataract had traumatic history at age from 2-9 years (mean: 5.1 years)
and the duration of visual deprivation due to cataract was from 8 to 30 years
(mean: 12 years). Thirteen cases with dilateral congenital cataract had 17.4
years (from 3 to 37 years) of visual deprivation. CONCLUSION: The deprivation of
form vision due to cataracts in childhood leads to increase in axial length and
myopia.
PMID- 9639839
TI - Refractive changes in chicks with form-deprivation myopia.
AB - PURPOSE: To study the refractive changes of form deprivation of myopia. METHODS:
Haisaik chickens were used to establish the animal models of myopia. Monocular
eyelids were sutured for form deprivation on the 5th day after chickens birth.
The chickens were examined by optometer and the anteroposterior axis, transverse
and vertical diameters were measured by verniermicrometer. RESULTS: Form
deprivation leads to myopic refractive abnormality (P < 0.001). The ocular
anteroposterior axis (P < 0.005), transverse and vertical diameters lengthen (P <
0.05). CONCLUSION: Form deprivation is the main cause of the development of
myopia.
PMID- 9639840
TI - Surgical management of macular epiretinal membranes.
AB - PURPOSE: To evaluate the effects of surgical treatment on macular epiretinal
membranes. METHODS: Vitrectomy and membrane removal were undergone for idopathic
secondary macular epiretinal membrane. RESULTS: Fourteen eyes of 15 patients
(93%) had vision improvement after operation in which 8 eyes (57%) increased 3 or
more Senellen lines. Only one case suffered from paracentral scotoma. No other
complications were noted. CONCLUSION: Surgical management of macular epiretinal
membrane is safe and effective with good visual outcome and few complications.
PMID- 9639841
TI - In vivo observations and electron microscopy of treatment of experimental HSV
keratitis with anti-HSV monoclonal antibodies.
AB - PURPOSE: To study the antiviral activity of monoclonal antibodies (McAb) in vivo
and identify their effects on experimental herpetic keratitis. METHODS: Topical
use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute
herpetic keratitis of rabbits infected by HSV-1 SM44. The application of the eye
drops in each group was five times per day for 14 days by double-blind method. In
vivo observation and electron microscopy were performed during the whole
procedure. The anti-HSV McAb's solution was mixed up of five monoclonal
antibodies with high neutrilization titers and/or high ADCC activity. RESULTS:
Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically
significant reduction of herpetic corneal epithelial lesion on rabbits from day 3
to day 14 postinnoculation (P < 0.01). Punctate and short dendritic lesion were
the main patterns. The area of involvement was also limited. Electron microscopic
analysis showed ultrastructural changes of herpetic corneal infection. The
clumping of nuclear chromatin, swollon nuclei, reduction of microflament,
rounding of epithelial cells were apparent in placebo-treated eyes. The advanced
lesion of the viral infection was karyolysis, karyoklasis and disruption of cells
in both scanning and transmission electron micrographes. The management of the
McAb-treated eyes showed that the pathological involvements as mentioned above
reduced remarkably. CONCLUSION: Topical application of anti-HSV monoclonal
antibodies produced marked antiviral effects in inhibiting the development of
experimental herpetic keratitis in rabbits and in protecting the susceptible
corneal cells. As a new biological product, the anti-HSV monoclonal antibodies
may provide a new approach to the treatment of HSV keratits.
PMID- 9639842
TI - Detection of RB germline mutations using exon-by-exon heteroduplex analysis
compared with SSCP.
AB - PURPOSE: To compare heteroduplex analysis with SSCP and to develop a simple and
effective method for mutational screening of RB gene. MATERIALS AND METHODS:
Leukocyte DNA was prepared from 12 unrelated Japanese patients with hereditary
retinoblstoma. PCR combined with simultaneous nonisotopic heteroduplex and SSCP
analysis was used to screen leukocyte DNA for such mutations, exon-by-exon,
without the use of restriction endonuclease digestion. PCR was conducted using 28
pairs of primers flanking all 27 exons and the promoter region of the RB gene,
with PCR products ranging from 159bp to 326bp. Mutations were identified by
sequencing. RESULTS: Heterozygous germline mutations were detected in 8 of 12
Japanese patients. The mutations were identified by sequencing as follows: G-
>C/acceptor of exon 11, T insertion/codon 389, C-->T/codon 455, 33bp
insertion/codon 455 (C decreases GA), G-->T/codon 533, C-->T/codon 579, C
deletion/codon 674, and C-->T/codon 787. CONCLUSION: Our results suggest that
small RB gene mutations are common. Heteroduplex analysis has advantage over SSCP
and they may complement each other for the rapid detection of unknown mutations.
PMID- 9639843
TI - Combined argon and Nd: YAG laser peripheral iridectomy: A new approach in
clinical practice.
AB - PURPOSE: To evaluate the therapeutic effect of combined argon and Nd: YAG laser
peripheral iridectomy. METHODS: 151 cases (200 eyes) of primary angle-closure
glaucoma and combined glaucoma were treated by combined procedure. Argon laser
was the first used to create partial iridectomy in 2/3-3/4 thickness without
penetrating pigmented epithelium, and then Nd: YAG laser was required to complete
a patent iridectomy. RESULTS: A successful iridectomy was achieved in all
patients independent of any type of irides (100%). Iris penetration rate in one
session presented in 95.0%. Complications appeared to be less common in our
patients: iris bleeding was only seen in 5.0% cases; the postoperative
inflammation was mild; corneal burns, localized lenticular opacities and closure
of iridectomies were less frequent. The follow-up ranged from 3m to 6.5 years.
The success rate in controlling IOP with/without medications were 99.0% except 2
eye failure. No attack occurred in 129 eyes with prophylactic laser therapy
during the periods of follow-up. CONCLUSION: Combined procedure had much more
advantage over either the argon or Nd: YAG laser iridectomy. It tended to be more
preferable for Asian patients with heavily pigmented and thick irides.
PMID- 9639844
TI - Corneal topography research of myopia in Chinese.
AB - PURPOSE: To determine corneal topography parameters of myopia in Chinese and help
for studies of causes of myopia, distingiush other corneal diseases (such as
early keratoconus), further explore the accurateness and safeness of the clinical
effects of radil keratotomy (RK) or photorefractive keratectomy (PRK). METHODS:
Fifty-eight eyes with mild or moderate myopia were examined by computer-assisted
photokeratography. (TMS-1 Computed Anatomy Inc. New York. NY) RESULTS: The
corneal topography of most (68%) of the examined eyes showed symmetric bowtie
pattern: the corneal surface of most (75%) of the examined eyes showed positive
aspheric shape (steeper centrally, flatter peripherally); the refractive power of
central cornea is at mean 44.165 +/- 1.429 D; the refractive difference between 1
to 25 ring in keratoscpe was at mean 1.655 +/- 0.785D; the mean SRI was 0.558 +/-
0.768, the mean SAI was 0.296 +/- 0.149; the mean Smik was 44.209 +/- 1.515D. The
apex and visual axis were dislocation in all the cornea examined. CONCLUSIONS:
The corneal surface refractive characterization of myopia might be relative to
the clinical effects of RK or PRK.
PMID- 9639845
TI - Ocular symptoms of tumors at sella turcica region.
AB - BACKGROUND: The sella tumors were found in 15% of intracranial tumors. The sella
turcica region locates in the base of skull, so the carcinoma patients in early
stage often showed no intracranial hypertension and other positive signs of
neural system. However, the patients presented visual field defect and hypopsia,
and often went to see the doctor of ophthalmology, which resulted from that the
tumor often compressed optic nerve and chiasm. We analysed the symptomatic
changes of the visual organs in order to provide a diagnostic basis for sellar
tumor in ophthalmological department. CLINICAL MATERIALS: Of the 407 cases of
sellar tumors, 296 were pituitary adenoma, 52 were craniopharyngioma, 43 were
meningioma, and the rest 16 were other kinds of sellar tumors. We analysed their
ocular changes of the sellar tumors and the characteristics of the tumors.
RESULTS: The sellar tumor in its early stage is mainly symptomized as visual
field changes. Visual field defect was found in 92.9% of pituitary adnoma, 75% of
craniopharyngioma and 34.8% meningioma patients. The patients of intermediate and
later sellar tumors gradually manifested the hypopsia and optic atrophy. Hypopsia
was found in 86.5% of pituitary adenoma patients, 89.9% of craniopharyngioma and
48.8% of meningioma patients. The morbidity rate of optic atrophy is 59.5% in
patients with pituitary adenoma, 65.5% of craniopharyngioma and 44.1% of
meningioma. CONCLUSION: The misdiagnostic rate of sellar tumor in
ophthalmological department still keeps comparatively high. The reason is that:
(1) The doctors lack the neuroophthalmological knowledge. (2) The patients were
not examined attentively enough. The ocular symptoms of sellar tumors are often
the first occurred and most important changes. In the clinical practice, all the
patients showing visual acuity and visual field disturbances should be examined
carefully (especially in visual field) and excluded ocular diseases, should be
transferred to the department of neurosurgery for further diagnosis and
treatment.
PMID- 9639846
TI - [Dynamic changes in soluble interleukin-2 receptor levels after rat corneal
allograft].
AB - PURPOSE: To evaluate the diagnostic utility of serum IL-2R level test in corneal
allograft rejection. METHODS: Serum soluble IL-2R was detected by
radioimmunoassay in rat corneal allograft model. RESULTS: Levels of soluble IL-2R
were markedly elevated prior to the clinical diagnosis of rejection. CONCLUSIONS:
Marked elevations of soluble IL-2R are associated with rejection, measurement of
soluble IL-2R may have a useful value in the early diagnosis of corneal allograft
rejection.
PMID- 9639847
TI - [Relationship between expression of P21ras and cellular DNA in pleomorphic
adenoma of lacrimal gland].
AB - BACKGROUND: The pleomorphic adenoma is the most frequent tumor of the human
lacrimal gland comprising about 50% of the epithelial tumors of this organ.
Although being benign, local recurrences can occur when the first removal was
incomplete and malignant transformation is also not in frequent. It is well known
that many sorts of cellular oncogene products are involved in the initiation,
promotion and progression of the human neoplasm. Our purpose was to know whether
there is abnormal expression of P21ras in pleomorphic adenoma. METHODS: We have
undertaken a study of the expression of P21ras in 5 normal tissues and 32
pleomorphic adenoma of lacrimal gland by immunohistochemical means using the
monoclone antibody F-132-62 and the nuclear DNA content in the tumor was assayed
by image analysis technique. RESULTS: Normal tissues of lacrimal gland were
negative, 12 tumors were stained positively with the antibody. The DNA content of
14 cases of tumor was increased. Their DNA ploidy distribution pattern showed two
or several peaks. Good correlation has been found between the expression of
P21ras and DNA ploidy distribution pattern, the DNA ploidy distribution pattern
of tumor which expressed p21ras showed mainly two or several peaks. P< 0.05.
CONCLUSIONS: The result of our studies may suggest that there are increased
expression of p21ras in pleomorphic adenoma and the expression of p21ras is
related to the promotion and progression of pleomorphic adenoma of lacrimal
gland.
PMID- 9639848
TI - [Study of pathogenesis of age-related macular degeneration].
AB - OBJECTIVES: To explore the pathogenesis of age-related macular degenerastion
(AMD) for its early prevention and treatment. METHODS: The enzymes of red blood
cells, levels of serum mineral elements and antiretinal antibodies were
determined in AMD and controls. Electronic microscopy, immunohistochemical survey
of the AMD patient subretinal neovascular membrane were performed. The light
exposure of animal experiment was also made. RESULTS: The levels of superoxide
dismutase and catalase as well as serum zinc were decreased in AMD patients, the
ratio of copper and zinc was increase. The retinal antibody reaction was higher
than that of controls, and the subretinal neovascular membrane showed
inflammatory granulomatous appearance. CONCLUSIONS: In addition to age, AMD may
be related to light damage, change in human defense system and chronic
inflammatory process.
PMID- 9639849
TI - [The study of the biological character on the culture of human trabecular
meshwork cells in vitro].
AB - PURPOSE: To establish the culture of human trabecular cells in vitro and to study
their biological character. METHOD: The trabecular specimens from human eyes were
cultured. The morphologic features of cultured cells were examined by light and
electron microscopy, the immunohistochemical characteristics and the
proliferative curve of the cultured cells were also investigated. RESULTS: The
primary cells in culture are multiangular or irregular, and the confluent
trabecular cells grow as a single cell layer. The junctions between trabecular
cells observed most frequently are puncta adherens and gap junction. Trabecular
cells showed apical villons projections and had a high density of various
organelles. The trabecular cells were stained intensely with monoclone antibodies
to fibronection and laminin and NSE. And it had negative reaction to monocolone
antibodies to VIII factor. The cultured cells showed a longer doubling time.
CONCLUSION: The culture of human trabecular cells in vitro was established. This
was a key step to dissect the trabecular specimen accurately and carefully.
According to the different cellular growth patterns and speed, morphologic and
immunohistochemical characteristics from that of the near cells, the cultured
human trabecular cells can been identified.
PMID- 9639850
TI - [Changes of the cornea induced by lipopolysaccharide in Lewis rats].
AB - PURPOSE: To investigate changes of the cornea induced by lipopolysaccharide
(LPS). METHODS: Immunohistochemical study using monoclonal antibodies to
monocytes, macrophages (ED1, ED2) and MHC class II antigen (OX6) was performed on
the corneal wholemounts obtained from normal lewis rats and those after LPS
injection. RESULTS: Macrophages were noted to be present in whole cornea with a
gradually decreased cell density from limbus to central part in normal lewis
rats. However, major histocompatibility complex class II antigen (MHC class II)
positive cells were only distributed at limbus. Footpad injection of LPS induced
an increase of monocytes and macrophages in whole cornea and a dramatical changes
of these cells morphologically. MHC class II-positive cells were only and shortly
noted on the surface of the cornea endothelium at early stage after LPS
injection. CONCLUSION: LPS-induced increase of macrophages in the cornea may be
an important defense mechanism in response to LPS challenge. On the other hand,
the absence of MHC class II-positive cells both in the normal and in the inflamed
cornea may be contributed to the stability of immunological microenvironment
within this tissue.
PMID- 9639851
TI - [The effect of mitomycin C on activities of carbonic anhydrase and ATPase of the
ciliary body epithelium in rabbit].
AB - PURPOSE: Enzymohistochemical methods were performed to observe the effect of
mitomycin C(MMC) on the activities of carbonic anhydrase (CA) and ATPase of the
ciliary body epithelium in rabbits after using 0.2mg/ml mitomycin C during
sclerectomy for the further study on the mechanism of the decrease of intraocular
pressure postoperatively. METHODS: 0.2mg/ml mitomycin C was topically applicated
during the sclerectomy in rabbit eyes. 7 days postoperatively, Hasson's method
and plumbum nitrate's method were used to stain the CA and ATPase of the ciliary
body epithelium. The grey value of the enzymes was quantitated by Image Analysor.
RESULTS: MMC inhibited the activities of CA and ATPase of the ciliary body
epithelium underlying the site of MMC application, but the difference of
enzymatic activities of the region 90 degree apart from the surgical site and
that of surgical site in normal saline control group was not statistically
obvious (P < 0.05). CONCLUSIONS: MMC could inhibit the activities of CA and
ATPase of ciliary body epithelium, thus leading to the decreased secretion of
humor aqueous and the lowerdown of intraocular pressure even persistent hypotony.
PMID- 9639852
TI - [The approach of cloned method in a human retinoblastoma cell line SO-Rb50].
AB - PURPOSE: In order to obtain the same characteristic tumor cells in genetical and
biological aspect, the cloned human retinoblastoma cell line SO-Rb50 established
in our department is reported in this paper. METHOD: SO-Rb50 cells were cloned in
multi-well plates. RESULT: Non-rosette Rb cells were successfully cloned while
rosette Rb cells failed. CONCLUSION: The result suggested that high
differentiated Rb cells were difficult to be cloned.
PMID- 9639853
TI - [Assessment of the toxicity of TAH on the cell lines of SO-Rb50 and SO-Rb70].
AB - PURPOSE: MTT assay was evaluated on cytoxicity for suspension growing cell lines
of SO-Rb50 and SO-Rb70, and the toxicity of TAH (the total alkaloid of peqanum
harmala L) on the above cell lines was assessed. METHODS: The relationships
between cell number and optical density, between optical density and exposure
time of MTT, and the stability of formazan crystal solution in MDSO were
determined. And the toxicity of TAH on the cell lines of SO-Rb50 and SO-Rb70 in
vitro with MTT assay was assessed. RESULTS: There was a direct proportional
relationship between the amount of cell number and its optical density; The
optical density increased gradully within 12 hours of the MTT incubation time;
The stable time of the formazan crystal solved in DMSO was 11 hours. The IC50
values (micrograms/ml) of TAH on SO-Rb50 were 10.66, 4.82 respectively for 48 and
72 hours; and on SO-Rb70 were 6.38, 4.2 respectively for 48 and 72 hours.
CONCLUSION: MTT assay can be used for suspension growing cell lines of SO-Rb50
and SO-Rb70: TAH has obvious toxicity to these two cell lines.
PMID- 9639854
TI - [The evaluation of oscillatory potentials of the electroretinogram in the early
diagnosis of the patients with primary open angle glaucoma].
AB - PURPOSE: To study the changes in the oscillatory potentials (OPs) of the
electroretinogram in the earlier or early stage of primary open angle glaucoma.
METHODS: OPs were recorded in thirty-three normal subjects (66 eyes) and 30
patients with primary open angle glaucoma (POAG) (58 eyes). The abnormal rates of
OPs in the different stages of POAG were analyzed and the sensitivity and the
specificity of OPs were also determined. RESULTS: The overall OPs amplitudes
(sigma o) were reduced in the patients with POAG and the amounts of small
wavelets were also decreased. The total abnormal rate of sigma o was 67.24%, and
42.86% in the earlier stage, 65.38% in the early stage and 76.00% in the advanced
and late stage. The sensitivity and the specificity of OPs were 67.24% and
92.42%. OPs had correlation with C/D. CONCLUSION: OPs can be considered as an
indicator of earlier or early diagnosis of patients with POAG before visual field
loss is detected.
PMID- 9639855
TI - [The study of local electroretinogram in age-related macular degeneration].
AB - PURPOSE: Observing the features of electro-activities at macular region in age
related macular degeneration (AMD), and evaluating the sensitivities of local
electroretinogram (LERG). METHODS: The LERG of 2.5, 5, 7.5 degrees at macula had
been recorded in 99 eyes (68 dry form, 31 wet form) of 80 AMD patients. The
contrast study had also been carried out with visual acuities and lesion areas at
the corresponding region. RESULTS: The results showed that there were no
significant differences between the decreased amplitudes of a and b waves of LERG
in dry form AMD with normal controls (P > 0. 05). While significant differences
existed in wet form AMD (P < 0.01). The changes of LERG at 2.5 degrees were
greater than those of the other two regions. The correlation study on b wave
amplitude and visual acuity of AMD patients showed that there was a positive
correlation existed between them only in wet form AMD at 2.5 degrees region (r =
0.516, P < 0.05). The negative correlations were observed between amplitudes of b
wave and lesion areas in wet form AMD at the three macular regions. Drusen of dry
form AMD had no effects on the amplitudes of LERG. CONCLUSIONS: The impairments
on macular function from two types of AMD are different. This study reveals that
the LERG is a sensitive method of visual electrophysiology for measuring macular
function. The smaller the testing area, the higher the sensitivity.
PMID- 9639856
TI - [Evaluation for grading standard of oblique flashlight test].
AB - PURPOSE: We try to study the validity and reliability of grading standard of
oblique flashlight test in this paper. METHODS: The validity of the grading
standard of the oblique flashlight test was evaluated in 251 eyes. Based on
anterior chamber angle as the gold standard, different grades of oblique
flashlight test can find capable of closure angle sensitivity and specificity.
The reliabilities (interobserver agreement and intraobserver agreement) also were
evaluated in 250 and 88 eyes. RESULTS: 1. Validity of grading standard of oblique
flashlight test: the results showed that it can find capable of closure angle
sensitivity is 96.67%, specificity is 74.53% and Youden's index is 0.712, when
the grades cutoff point on grade II. 2. Reliability of grading standard of
oblique flashlight test: the results showed that the intraobserver agreement was
observed agreement (Po) = 0.8, Kappa value (K) = 0.74 , Z = 22.48 and the
intraobserver agreement was Po = 0.909, K = 0.875, Z = 16.08. CONCLUSIONS: The
results of this research showed there are satisfactory validity and reliability
for grading standard of oblique flashlight test. The test may be applied widely
to estimate shallow anterior chamber and narrow angle.
PMID- 9639857
TI - [The comparative study of the macular light threshold in the normal and low
visual acuity people].
AB - PURPOSE: To test the macular light threshold (MLT) and the change of macular
light sensitivity (MLS) in the normal and low visual acuity people. METHODS: MLT
of 93 eyes of the normal and 76 eyes of low visual acuity people was measured
with macular threshold test of Humphrey Field Analyzer-640. RESULTS: 1. MLT
increases with age, there is a negative correlation between MLS and age 2. MLT of
low visual acuity people is significantly higher than that of the normal visual
acuity people in the same age group; 3. No significant difference of MLT was
found in the four quadrants of visual field in the same age group; 4. No
significant difference of MLT was found between male and female. CONCLUSIONS: MLS
of the normal visual acuity people is superior to that of the low visual acuity
people; MLS decreases with age.
PMID- 9639858
TI - [Effect of combining EGF with KGF on proliferation of human corneal epithelial
cells].
AB - OBJECTIVE: To select effective drugs for enhancing corneal epithelial wound
healing and treating persistent corneal epithelial defect. METHODS: Epidermal
growth factor (EGF) and keratinocyte growth factor (KGF) were added to cultures
of human corneal epithelial cells and DNA synthesis in corneal epithelial cells
were measured with [3H]-thymidine incorporation and liquid scintillation
techniques. The cells were counted in a hemocytometer to determine the doubling
time. RESULTS: 10 ng/ml EGF, 10 ng/ml KGF enhanced cellular proliferation
effectively (P < 0.01). EGF in combination with KGF, the enhancement was more
effective (P < 0.05) and reduced the doubling time. CONCLUSIONS: Our results
suggest that exogenous EGF with KGF can stimulate proliferation of human corneal
epithelial cells and it may be of potential use clinically for treatment of
persistent corneal epithelial
PMID- 9639859
TI - [Surgical treatment for congenital motive defect nystagmus by the parks (5, 6, 7,
8mm) procedure or the augmented Parks procedure].
AB - PURPOSE: The purpose of the surgical treatment for patients with congenital
motive detect nystagmus was to correct deviation of the eye and the head tilt, to
improve vision and eliminate nystagmus. METHODS: 19 patients underwent the Parks
(5, 6, 7, 8mm) or the augmented Parks procedure from 1987 to 1994. For patients
with abnormal head turn > or = 30 degrees, We used a 40-60% augmented Parks
procedure. RESULTS: A follow up of 19 patients ofr an average of 22 months
revealed a marked improvemtnts. After operation, the head turn was decreased form
30.5 degrees to 4.9 degrees, the intensity of nystagmus was decreased from 36.0
to 9.7, 21 eyes (55.3%) of 19 patients improved by two or more lines of Snellen
visual acuity. CONCLUSIONS: The Parks (5, 6, 7, 8mm) and the augmented Parks (5,
6, 7, 8mm) procedure produce a marked correction for congenital motive defect
nystagmus.
PMID- 9639860
TI - [A report of congenital giant defects in macular and choroid of both eyes].
PMID- 9639861
TI - 'Inclined abstainers': a problem for predicting health-related behaviour.
AB - A longitudinal test of the association between motivation to undertake a
precautionary health action and subsequent behaviour was conducted on women's
uptake of the cervical screening test. A sample of never-screened women (N = 166)
completed measures derived from protection-motivation theory (PMT; Rogers, 1983).
One year later, screening uptake was reliably determined from medical records.
While regression analyses demonstrated that PMT variables predicted both
motivation to undergo cervical screening and screening uptake, there was,
nonetheless, a good deal of inconsistency between protection motivation and
screening behaviour. Fifty-seven per cent of those who indicated they were
willing to undergo the test did not do so within a one-year period. Discriminant
analysis was therefore used to test the ability of cognitions specified by PMT to
distinguish four patterns of association between motivation and behaviour:
inclined actors, inclined abstainers, disinclined actors and disinclined
abstainers. While PMT variables could successfully classify the four groups, it
was not possible to derive a reliable discriminant function which distinguished
between inclined actors and inclined abstainers. The results suggest that PMT
provides a useful account of choice motivation but does not address the
psychological processes by which intention is translated into action. Recent
calls for the development of a social psychology of volition are discussed in the
light of these findings.
PMID- 9639862
TI - Thinking about one's gender group's privileges or disadvantages: consequences for
well-being in women and men.
AB - Thoughts about group-based privileges or disadvantages were expected to have
different consequences for personal and group well-being, depending on whether
the individual is a member of a high- or low-status group. To test this
hypothesis, women and men were randomly assigned to consider the ways that their
gender group membership has resulted in either beneficial or detrimental outcomes
in their lives. For men, thinking about their gender group's privileges resulted
in lower scores on the group-related well-being measures compared to women, and
thinking about their group's disadvantages resulted in higher personal self
esteem scores in men compared to women. It is suggested that among high-status
group members, thinking about privilege can evoke guilt and taint one's group
image, whereas thinking about disadvantage can augment personal internal
attributions for the positive outcomes received. Discussion focuses on the
implications that the operation of two types of mechanisms--group-based emotions
and the undermining or augmenting of attributions--has for the responses of high-
and low-status group members when their groups are portrayed as exerting either
negative or positive effects on their lives.
PMID- 9639863
TI - Are men more competitive than women?
AB - This study uses competition diaries to see whether women and men differ in (a)
what they compete over, (b) whom they compete with, and (c) their competitive
tactics, including use of aggression. In Study 1, university students kept
diaries of their competitive interactions during the term. Sex differences, few
overall, were as follows: (a) men's diaries contained more same-sex competition,
(b) women competed more about looking attractive whereas men competed more about
sports, and (c) men used physical (but not verbal) aggression more frequently
than women. In Study 2 strength of competition was also measured by
questionnaire. Women and men felt equally competitive overall, but men felt more
competitive about athletics and sexual attention whereas women felt more
competitive about looking attractive. In men, but not women, competitiveness for
financial success was correlated with various aspects of mating competition.
Young men were more competitive than older men in a variety of domains and were
also more physically and verbally aggressive, but no age difference in aggression
was found for women.
PMID- 9639864
TI - Do intentions predict condom use? Meta-analysis and examination of six moderator
variables.
AB - This study used meta-analysis to quantify the relationship between intentions and
behaviour in prospective studies of condom use. The effects of six moderator
variables were also examined: sexual orientation, gender, sample age, time
interval, intention versus expectation and condom use with 'steady' versus
'casual' partners. Literature searches revealed 28 hypotheses based on a total
sample of 2532 which could be included in the review. Overall, there was a medium
to strong sample-weighted average correlation between intentions and condom use
(r+ = .44), and this correlation was similar to the effect sizes obtained in
previous reviews. There were too few studies of gay men to permit meaningful
comparison of effect sizes between homosexual versus heterosexual samples. Gender
and measurement of intention did not moderate the intention-behaviour
relationship. However, shorter time intervals, older samples and condom use with
'steady' rather than 'casual' partners were each associated with stronger
correlations between intentions and condom use. Factors which might explain the
significant effects of moderator variables are discussed and implications of the
study for future research on intention-behaviour consistency are outlined.
PMID- 9639865
TI - A new class of cis-monobactam derivatives bearing a sulfamoyloxymethyl or an N
alkylsulfamoyloxymethyl group at position 4: synthesis and antibacterial
activity.
AB - A new series of monobactam derivatives, bearing unsubstituted or N
monosubstituted sulfamoyloxymethyl groups in position 4 was synthesized either in
racemic or in optically active form. Their in vitro antibacterial activity was
tested in comparison with carumonam 1a and its methoxyimino derivative 1b.
PMID- 9639866
TI - 1-Aminocylopropane-1-carboxylic acid derivatives as ligands at the glycine
binding site of the N-methyl-D-aspartate receptor.
AB - Several 1-aminocyclopropane-1-carboxylic acid derivatives were prepared and
tested for activity at the glycine-binding site of the N-methyl-D-aspartate
(NMDA) receptor complex. Structural modifications involved the amino group, the
carboxylic function or position 2 of the ring. When tested in a [3H]-MK-801
binding assay in the presence of glutamic acid, some of the compounds were able
to activate the receptor. Two of them (3e and 6) are selective ligands for the
glycine site of the NMDA receptor.
PMID- 9639867
TI - Synthesis and A1 and A2A adenosine binding activity of some pyrano[2,3-c]pyrazol
4-ones.
AB - A series of pyrano[2,3-c]pyrazol-4-ones was synthesized and evaluated for bovine
brain adenosine A1 and A2A receptor binding affinity. Substituents at positions 5
and/or 6 were varied in order to define the structure-activity relationships in
these new kinds of adenosine receptor ligands. The most selective and potent
ligand among the reported compounds was the 1,4-dihydro-1-phenyl-3-methyl-6-(3
aminophenyl)-pyrano[2,3-c]pyraz ol-4-one 11 which showed a 27-fold selectivity
for A1 receptor and a Ki value of 84 nM.
PMID- 9639868
TI - Variations in rat biochemical parameters after buckshot implant.
AB - Twenty eight albino Wistar rats were implanted with two 100 mg lead spheres: 14
received the implant in the peritoneum (P) and 14 in the thigh (T). Variations in
the activity of delta-aminolevulinic dehydratase (ALAD), of urinary delta
aminolevulinic acid (ALAU), of hematoporphyrins (HP) and of lead blood levels
(BPb) were then determined at 30, 60 and 90 days with respect to basal values.
Parallel determinations were performed by the same schedule in 7 rats implanted
with two glass beads and in 8 sham animals receiving surgical incision alone.
Techniques employed for ALAD were Berlin and Schaller; for ALAU, Tomokuni and
Ogata; for HP, Piomelli; and for BPb, atomic absorption spectrophotometry. As
indicators of lead presence, HP and ALAU proved better, both in P and in T rats.
The replacement of lead buckshot for small game hunting by other less toxic
elements is recommended.
PMID- 9639869
TI - Synthesis, antimicrobial activity and bleaching effect of some reaction products
of 4-oxo-4H-benzopyran-3-carboxaldehydes with aminobenzothiazoles and hydrazides.
AB - The synthesis of the biologically active novel systems derived from reaction of 3
formylchromones with three types of amino derivatives, 6-R2-2
aminobenzothiazoles, 6-amino-2-R3-thiobenzothiazoles and hydrazide derivatives
(derived from cyanoacetic, isonicotine, salicylic and gallic acids) was carried
out. The structures of the prepared compounds have been proved by elemental
analysis, 1H NMR and IR spectra. Antimicrobial activity was studied against the
following microorganisms--bacteria G+ (Staphylococcus aureus 29/58, Bacillus
subtilis 18/66), G- (Escherichia coli 326/71, Pseudomonas aeruginosa); yeasts:
Candida albicans, Saccharomyces cerevisiae; moulds: Microsporum gypseum,
Aspergillus niger, Scopulariopsis brevicaulis; and against typical and atypical
mycobacteria: Mycobacterium tuberculosis (H37Rv), Mycobacterium kansasii (PFG 8),
Mycobacterium avium (My 80/72), Mycobacterium fortuitum (1021). The hereditary
bleaching effect on the plastid system of Euglena gracilis, a unique phenomenon
of the biological activity of chromone derivatives, is reported. The bleaching
test on E. gracilis is used for detecting extranuclear mutations.
PMID- 9639870
TI - Synthesis of 1-methyl-4-(N-aroyl)-piperidinamides with anti-inflammatory and
analgesic activities.
AB - Two series of 1-methyl-4-(N-aroyl)-piperidinamides were synthesized and evaluated
for their anti-inflammatory and analgesic properties, as well as for their
gastrointestinal irritation liability. A non-aromatic derivative, 1-methyl-4-(N
cyclohexanoyl)-piperidinamide, was synthesized and evaluated in order to obtain a
more exhaustive knowledge of the structure-activity relationship.
PMID- 9639871
TI - Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4
methylenedioxy)phenylpropanal.
AB - Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal
were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea
pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation
to aldehyde using pyridinium dichromate (PDC) and condensation with five N
substituted derivatives of thiosemicarbazide. Tests were performed to evaluate
the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of
the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6
micrograms/ml, respectively.
PMID- 9639872
TI - Synthesis and preliminary antileukemic studies of cyclic mitoguazone analogues.
AB - Analogues of mitoguazone bearing a terminal amidino group as a part of the seven
membered ring of 1,3-diazepine and six-membered ring of pyrimidine were prepared
in order to evaluate in vivo antileukemic action towards L1210 leukemia in mice.
Preliminary pharmacological screening showed that the investigated compounds
increase the life span (T/C%) of the treated mice in comparison with the
untreated animals. The strongest antineoplastic effect was exhibited by compound
8.
PMID- 9639873
TI - A hydrophobic peptide (VAP-peptide) of the silkworm, Bombyx mori: structure,
expression and an enhancing function of diapause hormone activity.
AB - We have recently identified a unique lipophilic peptide (VAP-peptide) with
diapause egg inducing activity in the silkworm, Bombyx mori (Imai et al., 1996).
The cloning and sequencing of cDNA encoding VAP-peptide have demonstrated that
the deduced amino acid sequence consisted of 84 amino acid residues, from which
the mature VAP-peptide of 68 amino acid residues was released by cleaving a
signal sequence. Searches of the GenBank data base revealed no significant
sequence similarity to other proteins including diapause hormone (DH). VAP
peptide gene was selectively expressed just before and at adult eclosion in the
head and the thorax not in the abdomen. By a Western blot analysis, VAP-peptide
was also localized in the head and the thorax of adults. The purified recombinant
VAP-peptide could not induce diapause eggs even when injected at a high dose of
10 nmol/pupa. Whereas, injection of a mixture of VAP-peptide and DH clearly
decreased a half-maximum dose (ED50 value) and a threshold dose (TD value) of DH,
and these values decreased according to increasing molar ratios of VAP-peptide to
DH. Thus, the VAP-peptide is concluded to be an endogenous protein acting as a
potent enhancer of DH activity through interaction with DH.
PMID- 9639874
TI - G0/G1 cell cycle arrest in the brain of Sarcophaga crassipalpis during pupal
diapause and the expression pattern of the cell cycle regulator, proliferating
cell nuclear antigen.
AB - During pupal diapause in the flesh fly, Sarcophaga crassipalpis, the cells of the
brain are arrested in the G0/G1 phase of the cell cycle. When diapause is
terminated with a topical application of hexane, cell cycling is evident within
12 hours. Four G1 and S phase regulatory genes were examined by Northern blot
analysis to evaluate their expression patterns in relation to this cell cycle
arrest. A distinction between diapausing and nondiapausing individuals was noted
only for Proliferating Cell Nuclear Antigen (PCNA). PCNA was highly expressed
after diapause was terminated but not during diapause. In contrast, cyclin E,
p21, and p53 were expressed equally at all times. In situ hybridization using
PCNA probes further indicated a correlation between PCNA transcription
(expression) in the brain and cell cycling. Our evidence thus suggests a
potential role for PCNA as an important regulator of cell cycle arrest during
diapause.
PMID- 9639875
TI - TER94, a Drosophila homolog of the membrane fusion protein CDC48/p97, is
accumulated in nonproliferating cells: in the reproductive organs and in the
brain of the imago.
AB - We have cloned a Drosophila homolog of the membrane fusion protein CDC48/p97. The
open reading frame of the Drosophila homolog encodes an 801 amino acid long
protein (TER94), which shows high similarity to the known CDC48/p97 sequences.
The chromosomal position of TER94 is 46 C/D. TER94 is expressed in embryo, in
pupae and in imago, but is suppressed in larva. In the imago, the
immunoreactivity was exclusively present in the head and in the gonads of both
sexes. In the head the most striking staining was observed in the entire neuropil
of the mushroom body and in the antennal glomeruli. Besides TER94, sex-specific
forms were also detected in the gonads of the imago: p47 in the ovaries and p98
in the testis. TER94/p47 staining was observed in the nurse cells and often in
the oocytes, while TER94/p98 staining was present in the sperm bundles. On the
basis of its distribution we suggest that TER94 functions in the protein
transport utilizing endoplasmic reticulum and Golgi derived vesicles.
PMID- 9639876
TI - cDNA and deduced amino acid sequences of a peritrophic membrane glycoprotein,
'peritrophin-48', from the larvae of Lucilia cuprina.
AB - The gut of most insects is lined with a semi-permeable peritrophic membrane (or
peritrophic matrix) composed of chitin, proteoglycans and proteins. Despite the
probable importance of the peritrophic membrane in facilitating the digestive
process and protecting insects from invasion by micro-organisms and parasites,
there has been little characterization of the specific components and their
interactions within this acellular structure. Here we report the characterization
of an integral peritrophic membrane glycoprotein, peritrophin-48, from the larvae
of the fly Lucilia cuprina, a primary agent of cutaneous myiasis in sheep.
Peritrophin-48 was purified from peritrophic membrane obtained by larval culture
and its location within the peritrophic membrane determined by immuno
fluorescence and immuno-gold localizations. The cDNA coding for peritrophin-48
was cloned and sequenced. The deduced amino acid sequence codes for a protein of
375 amino acids containing an amino-terminal signal sequence followed by five
similar, but non-identical domains, each approximately 65-70 amino acids in
length and characterised by a specific register of six cysteines. The deduced
amino acid sequence shows significant similarity to two other peritrophic
membrane proteins, peritrophin-95 and peritrophin-44, from the same species. A
reverse transcriptase-PCR approach indicated that there are several highly
related peritrophin-48 genes expressed in each individual. Reverse transcriptase
PCR also demonstrated the expression of peritrophin-48 in all three larval
instars and adults but not pupae or eggs. Peritrophin-48 was expressed only by
the cardia and by the larval midgut. A simple structural model of a basic unit of
a type 2 peritrophic membrane is presented.
PMID- 9639877
TI - Characterization of two male-specific polypeptides in the tergal glands
secretions of the cockroach Leucophaea maderae (Dictyoptera, Blaberidae).
AB - During the sexual behavior of cockroaches, the female mounts the courting male to
feed on the proteinaceous secretion of the tergal glands. Polyacrylamide gel
electrophoresis of male and female protein extracts after cuticle wiping revealed
three major bands. Two of 18 and 22 kDa, named Lma-P18 and Lma-P22, are specific
to the male tergal extracts. Moreover, Lma-P22 is only found in the male second
tergite extracts. The third one of 54 kDa, named Lma-P54, is common to male and
female extracts and could be considered as an ubiquitous surface protein. Several
other minor proteins are also present on the body surface of adults of both
sexes. Quantitation of the total protein amount of the male tergal gland
secretion shows a progressive accumulation from adult ecdysis to sexual maturity.
Western blot analysis using antibodies raised against Lma-P22 and Lma-P54
confirms that Lma-P22 is only secreted by the male second tergite glands.
Immunohistolocalization demonstrates that these three major proteins are produced
by class 3 glandular cells.
PMID- 9639878
TI - Micropellicular stationary phases for high-performance liquid chromatography of
double-stranded DNA.
AB - The central role of nucleic acids in biosciences has effectuated the rapid
development of numerous techniques for their isolation, separation,
characterization and quantitation. Advances in high-performance liquid
chromatography, particularly the introduction of novel microparticulate sorbents,
have greatly promoted the separation and quantitation of nucleic acids. Because
of their favorable mass transfer properties, micropellicular packing materials
are advantageous for fast and high-resolution separations of double-stranded (ds)
DNA molecules. With micropellicular packings, anion-exchange and ion-pair
reversed-phase chromatography are the most popular chromatographic separation
modes for dsDNA. The effective separation mechanisms in both chromatographic
techniques are preferably described by nonstoichiometric models, that are founded
on a better physicochemical background than traditional stoichiometric models.
Column efficiency, retention characteristics, and size or sequence dependency of
retention of dsDNA are greatly influenced by the chosen operational variables in
both chromatographic modes. The applicability of HPLC with micropellicular
stationary phases nucleic acids research includes preparative DNA fractionation,
DNA restriction mapping, analysis of polymerase chain reaction products and
purification of plasmid DNA.
PMID- 9639879
TI - Preparative purification of supercoiled plasmid DNA using anion-exchange
chromatography.
AB - Large scale manufacturing of gene vectors such as plasmid DNA is an important
issue in gene therapy. Anion-exchange chromatography is fundamental in the
downstream processing of plasmids both as a process and analytical technique.
This work reports the use of Q-Sepharose columns (1, 10 and 40 ml) for the
preparative purification of plasmid pUC18. NaCl gradient elution enabled the
isolation of supercoiled plasmid from low-M(r) RNA, cDNA and plasmid variants. A
compact covalently closed, supercoiled form of denatured plasmid carrying large
stretches of single-stranded DNA was identified as one of the major contaminants.
Anion-exchange HPLC on a Poros QE 20 column was used to quantify plasmid yield.
Supercoiled plasmid was recovered in a single fraction with a 62 +/- 8% yield.
Loadings higher than 40 micrograms/ml gel could be used but at the expense of a
loss of resolution between open circular and supercoiled forms. Plasmid quality
was evaluated by gel electrophoresis, restriction analysis, transformation
experiments and protein assays.
PMID- 9639880
TI - Quantitative analysis of gene expression by ion-pair high-performance liquid
chromatography.
AB - We have analyzed the utility of ion-pair reversed-phase HPLC for gene
quantification by competitive reverse transcriptase polymerase chain reaction (RT
PCR). Competitive RT-PCR reactions employed various RNA competitors which shared
high sequence similarity to the native transcripts for which they served as
references. Competitive reactions resulted in the detection of two reaction
products when reactions were analyzed by agarose gel electrophoresis, but three
products when analyzed by HPLC. The third product was demonstrated to be a
heteroduplex formed between mixed strands of native and competitor amplicons.
Mathematical analysis of these competitive reactions indicated that
identification and quantification of the heteroduplexes were essential to produce
accurate gene quantification. PCR amplification efficiency was shown to be
identical for native and competitor transcripts. However, RT efficiency
differences were observed which may be sequence dependent. These differences were
highly consistent across reactions for the same native and competitor inputs.
Increasing the sequence similarity resulted in a competitor which had the same RT
efficiency as the native transcript. Titration of various levels of competitor
against native RNA resulted in the expected linear relationships which had slopes
of unity. Quantitation could be performed with similar precision in single tube
comparisons in which the initial abundance of the native transcript was
calculated by knowledge of the final reaction product ratio and the initial
competitor input level. The assay system is highly accurate, i.e. the measured
level of gene expression reflected the actual copy number of the gene present in
the sample. This was demonstrated by performing reactions in which known amounts
of native transcript were quantified and the amount estimated by the assay was
shown to be the same as the known amount added to the reaction. A similar
approach has been devised for examining the relative levels of alternatively
spliced isoforms. In this system, primers were selected to produce reaction
products which served as their own internal competitors (by spanning the
alternative splice site). Hormonal dependence of the ratio of abundance of two
isoforms of the rabbit RUSH-1 gene was demonstrated.
PMID- 9639881
TI - Separation of oligonucleosomal DNA fragments from apoptotic animal cells using a
triad of Sephacryl columns.
AB - The degradation of DNA, resulting in information of oligonucleosomal fragments,
is a characteristic feature of apoptosis, i.e., the process of programmed cell
death. In this work we have developed a method for exact determination of the
proportion of fragmented DNA in an apoptotic cell population. To this end we
employed Sephacryl gel chromatography matrices and UV detection of DNA
concentration. The disturbing effect of low-molecular-mass UV-absorbing
contaminants was eliminated by insertion of a Sephacryl S-200 HR pre-column.
Optimum resolution of DNA samples isolated from apoptotic cells was achieved
using a triad of Sephacryl S-200 HR, Sephacryl S-500 HR and Sephacryl S-1000 SF
columns.
PMID- 9639882
TI - N-hydroxysuccinimide ester labeling 5'-aminoalkyl DNA oligomers: reaction
conditions and purification.
AB - Difficulties were encountered in labeling 5'-aminoalkyl DNA oligomers with
glycolketo electrophore N-hydroxysuccinimide esters in aqueous sodium bicarbonate
(a common base for this purpose), followed by C18-silica reversed-phase high
performance liquid chromatography (HPLC) to achieve purification. The
electrophore-labeled oligomers were not separated readily either from the
hydrolyzed electrophore or from the starting oligomer. This problem was overcome
by conducting the reaction with triethylamine as a base, organic washing the
reaction mixtures after evaporation, and separating on a C18-poly(styrene
divinylbenzene) HPLC packing.
PMID- 9639883
TI - Analysis of clinically relevant, diagnostic DNA by capillary zone and double
gradient gel slab electrophoresis.
AB - A number of applications of capillary zone electrophoresis (CZE) in sieving
liquid polymers (notably linear polyacrylamides and cellulose) for the analysis
of polymerase chain reaction products of clinically relevant, diagnostic DNA, are
reviewed here. The fields covered are human genetics, quantitative gene dosage,
microbiology and virology, forensic medicine and therapeutic DNA (notably
antisense nucleotides). Some unique, novel developments are highlighted, such as
(a) non-isocratic CZE, i.e., temperature-programmed CZE for detection of DNA
point mutations and (b) the synthesis of novel N-substituted acrylamides,
offering extreme resistance to alkaline hydrolysis, coupled with high
hydrophilicity. In the field of denaturing gradient gel electrophoresis (DGGE),
as routinely performed in gel slabs, a novel methodology is described, i.e.,
double-gradient DGGE. In this technique, two gradients are simultaneously applied
along the migration direction; a chemical denaturing gradient, for partially
unwinding homo- and hetero-duplexes of DNA and a porosity gradient, for re
compacting diffuse bands melting over a broader range of denaturing conditions.
Both the CZE and the slab gel methodologies, with the latest developments
described in this review, appear to be promising tools for screening diagnostic
DNA.
PMID- 9639885
TI - Comparison of slab gel electrophoresis and capillary electrophoresis for the
detection of the fluorescently labeled polymerase chain reaction products of
short tandem repeat fragments.
AB - The sizing capability of slab gel electrophoresis for short tandem repeat (STR)
fragments was compared to the sizing capability of capillary electrophoresis
(CE). Both systems used automated laser fluorescence detection to detect four
fluorescent dyes, enabling the use of an internal lane standard within each
sample. The STR fragments were amplified using a multiplex polymerase chain
reaction (PCR) in which the STR fragments Hum CD-4, Hum TH01, Hum D21S11 and Hum
SE33 were amplified simultaneously. The reproducibility of the size calling was
determined for both systems. The average standard deviation obtained for the slab
gel system was 0.2, which was comparable to the standard deviation of 0.12
obtained for the CE system. The CE system produced results comparable to those
obtained on the slab gel system, with a level of precision of +/- 1.0 bp (between
instruments).
PMID- 9639884
TI - Contamination-free and automated composition of a reaction mixture for nucleic
acid amplification using a capillary electrophoresis apparatus.
AB - The acceptance of the polymerase chain reaction (PCR) as an amplification method
in molecular diagnostics and the rapid development of capillary electrophoresis
(CE) as an analysis method of those PCR products was a reason for us to
investigate further integration of those two techniques. Using a fused-silica
capillary as a pipette we were able to compose a PCR mixture in the CE apparatus.
Because a capillary can be thoroughly rinsed and the CE apparatus is a closed
system, the risk of contamination and therefore the occurrence of false positive
results is minimized. The fact that a CE system can be fully automated
contributes to a more reproducible and standardized PCR composition protocol.
PMID- 9639886
TI - Fast DNA separations using poly(ethylene oxide) in non-denaturing medium with
temperature programming.
AB - We demonstrated fast DNA separations in low viscosity entangled solutions with a
temperature gradient in a non-denaturing separation medium. The separations were
carried out in a solution of commercially available poly(ethylene oxide) (PEO) [1
x Tris(hydroxymethyl)aminomethane borate buffer, without urea] with a temperature
gradient of 2 degrees C/min. The performance was compared with that of a solution
of PEO with urea at ambient temperature. We found that the former condition gives
sufficient resolution for accurate base calling and that in general, it gave
better separation for fragments larger than 450 base pairs (bp). Most
importantly, the separation speed approaches 30 bp/min. In addition, we describe
a simple yet reliable gel preparation protocol for such separations.
PMID- 9639887
TI - Separation of pd(GC)12 from pd(AT)12 by free solution capillary electrophoresis.
AB - The two synthetic self complementary oligonucleotides pd(AT)12 and pd(GC)12 were
separated by free solution capillary electrophoresis (CZE) using simple borate
buffers. The effects of pH (7.5-9) and the concentration of the buffer (0.03-0.35
M) were investigated. Higher pH values and buffer concentrations led to better
resolution and longer migration times, the pH having a more pronounced effect on
the separation than the concentration of the buffer. It is proposed that the
conformation and effective length of the oligonucleotides may have a role in
their separation in free solution capillary electrophoresis.
PMID- 9639888
TI - Detecting single base substitutions, mismatches and bulges in DNA by temperature
gradient gel electrophoresis and related methods.
AB - Temperature gradient gel electrophoresis (TGGE) and related methods can separate
DNA fragments that differ by a single base pair or defect. This article describes
the basic features of TGGE, and reviews the theoretical model of DNA unwinding
and its ability to predict DNA mobility in a temperature gradient gel. Recent
applications of TGGE and related methods that were directed at detecting point
mutations, and evaluating the effects of single site defects are also reported.
PMID- 9639889
TI - Comparison of DNA migrations in two clamped homogeneous electric field chambers
of different sizes. Relation between sample thickness and electrophoresis time.
AB - We present here a method to compare the mathematical descriptions of DNA
migration per pulse as a function of pulse time. It is based on obtaining robust
estimates and variances of DNA reorientation time, migration velocities during
and after DNA reorientation; and on the statistical comparisons of these
estimates. We demonstrated an equal description for the migration per pulse of
each DNA molecule separated under identical conditions in clamped homogeneous
electric field (CHEF) and miniCHEF chambers. However, miniCHEF resolved the
patterns in shorter times, because it uses thinner samples. The relationship
between sample thickness and CHEF run time is also presented.
PMID- 9639890
TI - Detection of gene expression in single neurons by patch-clamp and single-cell
reverse transcriptase polymerase chain reaction.
AB - Detection and quantitation of gene expression in single cells is especially
important in the central nervous system where, at the cellular level, the synapse
can be considered the single functional unit. For example, the consolidation of
long-term memories may be mediated by persistent changes in the strength of
synaptic transmission at individual synapses. In order to investigate the
requirement for de novo RNA synthesis during long-term potentiation in individual
neurons, we have combined single-cell electrophysiology with single-cell gene
expression methodology. Described are methods combining whole-cell patch-clamp
and single-cell RT-PCR for the detection of a single mRNA species for nitric
oxide synthase, or, through a multiplex strategy, for the simultaneous detection
of several mRNAs including heme oxygenase 2, protein phosphatase inhibitor 1
protein, and several isoforms of the calcium/calmodulin dependent protein kinase
II.
PMID- 9639891
TI - High resolution free chromatin/DNA fiber fluorescent in situ hybridization.
AB - High resolution chromatin/DNA fiber fluorescent in situ hybridisation (FISH) is a
powerful system for physical mapping and genome research. With direct
visualisation of molecular probes along released chromatin or DNA fiber, fiber
FISH has become the method of choice to order genes or DNA markers within
chromosomal regions of interest. Combined with DNA-protein in situ codetection
fiber FISH shall play a more important role for analysis of genome function. In
this paper the concept and technical developments of fiber FISH are reviewed with
the emphasis of comparison on the various protocols. Future challenges are also
discussed along with the highlights of the successful applications achieved by
fiber FISH methodology.
PMID- 9639892
TI - Development of guanine analyzer to measure activity of guanylate cyclase.
AB - A previous analyzer of adenine compounds by high-performance liquid
chromatography was converted for the determination of guanine, its nucleoside and
nucleotides by a post-column fluorescence derivatization with phenylglyoxal (PGO)
in place of bromoacetoaldehyde. The gel filtration column (Asahipak GS-320H) was
used for separation by a mobile phase consisting of 25 mM sodium citrate buffered
(pH 4.0)-150 mM NaCl solution and CH3CN (85:15, v/v) containing 15 mM PGO. The
separated analytes reacted with flow through PGO in a reaction coil at 90 degrees
C into fluorescent derivatives. Those derivatives were detected fluorimetrically,
highly selective and quantitatively. The activity of soluble guanylate cyclase
(sGC) in the neuroblastoma N1E-115 cell was measured by tracing the peak height
of cGMP synthesized from substrate GTP using this guanine analyzer. The
sensitivity of the present method was lower than the radioisotope method.
However, our modified method was simpler, safer and quicker than the radioisotope
method. Furthermore, this method could trace other guanine compounds
simultaneously, allowing measurement of guanine metabolizing enzymatic activity.
Therefore, it will be useful for screening of effectors on sGC.
PMID- 9639894
TI - Temperature dependent population growth of Gyrodactylus derjavini on rainbow
trout, Oncorhynchus mykiss.
AB - Rainbow trout were experimentally infected with the ectoparasitic monogenean
Gyrodactylus derjavini at three temperatures, 5.5 degrees C, 11.6 degrees C and
18.7 degrees C. Subsequently, the infection level was monitored during the
following 6 weeks. The population growth was positively correlated with
temperature in the initial part of the investigation. At 18.7 degrees C growth of
the parasite population was fast reaching a peak abundance within 3 weeks,
whereafter the infection level decreased significantly. Peak abundance was
recorded in week 5 at 11.6 degrees C. A very slow but steady parasite
reproduction was noted at 5.5 degrees C, but no peak abundance was reached within
6 weeks. The decline in parasite population after reaching peak levels is likely
to be caused by a host response. The host response is also indicated by the
parasites' active selection of particular microhabitats. This anti-monogenean
response developed fastest at 18.7 degrees C, more slowly at 11.6 degrees C and
was not recorded within 6 weeks at 5.5 degrees C.
PMID- 9639893
TI - Analysis of T cell populations and IL-3 mRNA expression in mesenteric lymph node
cells and intestinal intraepithelial lymphocytes in Strongyloides ratti-infected
mice.
AB - T cell populations and IL-3 mRNA expression were analysed in mesenteric lymph
node cells and intestinal intraepithelial lymphocytes (IEL) in Strongyloides
ratti-infected mice. On days 7 and 12 post-infection, 2.6 times as many
mesenteric lymph node cells were present in S. ratti-infected mice compared with
uninfected mice. Although the percentages of CD3+, CD4+ and CD8+ cells decreased
during infection, the absolute numbers of these cell types increased on day 7 due
to an overall increase in the mesenteric lymph node cell number. The CD4/CD8
ratio in IEL was increased on day 5, whereas no significant change in the CD4/CD8
ratio was observed in the mesenteric lymph node cells. Expression of IL-3 mRNA,
which is an important cytokine for the induction of murine mucosal mastocytosis
and S. ratti-expulsion, was examined in mesenteric lymph nodes and IEL of
uninfected and infected mice. IL-3 mRNA was detected in mesenteric lymph nodes of
S. ratti-infected mice but not detected in the lymph nodes of uninfected mice. IL
3 mRNA was detected in IEL from both infected and uninfected mice with an 20-fold
increase in expression in IEL of infected mice. Overall, IL-3 mRNA levels were
higher in IEL than in mesenteric lymph nodes following S. ratti-infection.
Expression of IL-4, IL-10, stem cell factor (SCF or c-kit ligand) and IFN-gamma
mRNA was also examined in these two tissues. IL-10 mRNA was not detected in any
tissue examined and IFN-gamma mRNA levels were unaltered as a result of an S.
ratti-infection. Elevated expression of mRNA for SCF (5-fold) and IL-4 (20-fold)
was observed in the mesenteric lymph nodes of infected mice. In contrast, SCF
mRNA levels were similar in IEL of uninfected and infected animals and only a
modest increase in IL-4 mRNA was observed in IEL of infected mice.
PMID- 9639895
TI - Gastrointestinal and pulmonary nematode infections decrease goat productivity in
Moroccan semi-arid conditions.
AB - A herd of goats naturally infected with lungworm and gastrointestinal nematodes
was divided into three groups and treated with either morantel tartrate or
fenbendazole at strategic periods, i.e. in June (at pre-mating), in November (at
pre-kidding) and in January (at early lactation) or left untreated. Morantel
tartrate treatment (8 mg kg-1) was efficient in reducing the gastrointestinal
nematode egg output and fenbendazole treatment (15 mg kg-1) was efficient in
reducing the gastrointestinal nematode egg and small lungworm larvae faecal
output. Reductions in mortality of adult goats and their progeny and improvement
of rearing percentages were recorded in both treated groups, with fenbendazole
showing a greater response than morantel tartrate. A relative risk analysis
showed that mortality in goats and kids was significantly reduced in treated kids
and goats. Reduction of 6.6% in kidding rates, 0.21 in prolificacy, and an
increase of 1.3 in abortion rates, 8.3% in kid and 2.2% in goat mortalities,
could be attributable to the small lungworm infection. Small lungworm infections
seem therefore to be one of the main causes of indirect kid mortality and
inadequate breeding performance of goats in the semi-arid Middle Atlas region of
Morocco.
PMID- 9639896
TI - Dung-derived biological agents associated with reduced numbers of infective
larvae of equine strongyles in faecal cultures.
AB - Two sets of dung-derived organisms from soil routinely fertilized with manure
(MA) and soil chemically fertilized (CH) were cultured separately in the
laboratory. Baermannized organisms from these cultures were added to 20 g of
faeces from strongyle-infected horses to form three treatment groups: (i) no soil
organisms; (ii) low inoculum of soil organisms containing all organisms present
in a suspension of approximately 100 adult female free-living nematodes; and
(iii) high inoculum containing those soil organisms present with approximately
1000 adult female free-living nematodes. Three studies were conducted using MA
cultures and faeces containing 50 stronglye epg, CH cultures and faeces
containing 1500 strongyle epg, and a mixture of soil organisms from the two
cultures (MC) and faeces containing 600 strongyle epg. Within each study, five
control cultures and 15 each of low and high inoculum cultures were prepared and
incubated at 24 degrees C and 95% humidity in a climate chamber for 15 days.
Parasitic and free-living nematodes were then recovered by the Baermann technique
and counted. The numbers of third stage larvae were significantly lower in the
high inoculum group compared to controls. The percent reductions in the number of
third stage larvae for the low and high inoculum groups were 63.6% and 90.9%,
85.1% and 97.1%, 84.5% and 98.4% for MA, CH, and MC studies, respectively,
indicating that mortality increased with the number of soil organisms added to
cultures. Examination of the source cultures detected the presence of two species
of nematophagous fungi and three genera of free-living nematodes reported to be
predacious.
PMID- 9639897
TI - Prevalence of cystic echinococcosis in camels (Camelus dromedarius) in Libya.
AB - In an abattoir study, 514 camels, slaughtered for meat production in different
areas of northern Libya were examined for the presence of cystic echinococcosis
(CE). In addition, 367 sheep and 184 goats were examined. The overall prevalence
of infection with CE was 48% in camels, 15.8% in sheep and 3.8% in goats. The
infection rate, number and size of cysts were significantly higher in older
camels. In six city abattoirs across northern Libya, i.e. Zawia, Tripoli, El
Khumes, Mesurata, Sirt and Benghazi, the prevalence rate of infection in camels
ranged from 38.7% to 55.2%, in comparison with sheep and goat rates which were
between 0% and 37.9% and 0% and 8.2%, respectively. In camels, the lungs were the
most frequently infected organs (85.4%) with liver cysts occurring at a
significantly lower rate (33%). In contrast, the liver was the predominant
infected site with prevalence values of 86% and 100% in sheep and goats,
respectively. More than 90% of camel hydatid cysts were fertile. The possible
role of camels in the transmission of CE in Libya is discussed.
PMID- 9639898
TI - Histopathology of Sanguinicola inermis infection in carp, Cyprinus carpio.
AB - The histopathological response of carp to Sanguinicola inermis was investigated
by serial sectioning laboratory infected fish up to 90 days post infection (d
p.i.). Juvenile flukes and adults caused mechanical damage to tissues during
invasion and migration up to 28 d p.i. Adults partially occluded blood vessels
and may have reduced blood circulation. In the initial phase of egg production
(28-42 d p.i.), eggs and emigrating miracidia in gill tissue caused breakdown of
vascular integrity, necrosis, hyperplasia, haemorrhage and eosinophilic
infiltration of epithelial tissue. After 42 d p.i. the host granulomatous
inflammatory response encapsulated eggs lodged in the gills, visceral sites and
connective tissue displacing normal tissue. Encapsulation and subsequent
degradation of eggs and miracidia within granulomata was highly developed by 90 d
p.i. Laboratory infections of S. inermis can induce respiratory distress and
therefore impair respiration of fish. The parasite also caused pathological
changes in osmoregulatory, excretory and haemopoietic tissue and may impair
function in these organ systems.
PMID- 9639899
TI - Tests on the centrifugal flotation technique and its use in estimating the
prevalence of Toxocara in soil samples from urban and suburban areas of Malaysia.
AB - The influence of soil texture (silt, sand and laterite) and flotation solutions
(saturated NaCl, sucrose, NaNO3, and ZnSO4) upon the recovery of Toxocara ova
from seeded soil samples with the centrifugal flotation technique was
investigated. Soil samples of different texture were artificially seeded with
Toxocara spp. ova and subjected to a centrifugal flotation technique which used
various flotation solutions. The results showed significant (P < 0.001)
interactions between the soil types and the flotation solutions. The highest
percentage of ova recovery was obtained with silty soil (34.9-100.8%) with
saturated NaCl as the flotation solution (45.3-100.8%). A combination of washing
of soil samples with 0.1% Tween 80, and flotation using saturated NaCl and a 30
min coverslip recovery period was used to study the prevalence of contamination
of soil samples. Forty-six soil samples were collected from up to 24 public
parks/playgrounds in urban areas of Petaling Jaya and suburban areas of Serdang.
The prevalence of Toxocara species in the urban and suburban areas was 54.5% and
45.8% respectively.
PMID- 9639900
TI - Recovery from arrhythmias in lambs infected with Strongyloides papillosus
following worm elimination.
AB - Calves and lambs heavily infected with Strongyloides papillosus develop cardiac
arrest by ventricular fibrillation which is preceded by continuous sinus
tachycardia and prolongation of the PQ interval during the patent infection. In
the present study, cardiac rhythms following anthelmintic treatment were
investigated in lambs infected with S. papillosus to ascertain whether cardiac
disorders due to the infection are based on a reversible and curable change.
Eight lambs were given a lethal dose of S. papillosus. Five of the animals were
injected with ivermectin when they developed continuous sinus tachycardia and
prolongation of the PQ interval. The other three animals served as untreated
controls. In the treated animals, elevated heart rates and PQ intervals began to
decrease between 10 and 21 h, then continuous sinus tachycardia and prolongation
of PQ interval disappeared within 39 h of treatment. No arrhythmias were detected
after the disappearance of sinus tachycardia. Faecal egg counts became negative
within 61 h of treatment. Only a few worms were collected from the small
intestine at necropsy. The control animals developed ventricular fibrillation by
349 h after infection, having high faecal egg counts and intestinal worm burdens.
These results indicate that cardiac disorders generated by S. papillosus
infection are reversible and curable following worm elimination.
PMID- 9639901
TI - Epidemiology of trichinellosis in lynx in Finland.
AB - Three hundred and twenty seven European lynx (Lynx lynx) were examined for
Trichinella sp. larvae using the muscle digestion method. The animals were of
both sexes, various ages, and collected between 1989 and 1994 in different
locations in Finland. Forty percent of them (132) were found to be infected.
Infection was overdispersed, so that the majority of infected lynx only harboured
small amounts of larvae, while a minority had higher densities of infection, but
never significantly exceeding 40 larvae per gram of muscle (lpg). The median
density of infection was 1.04 lpg. To find factor statistically associated with
the risk of infection, multivariate logistic regression analysis was performed.
Male sex, increasing age, and the density of raccoon dog population in the area
were all significantly associated with infection. However, the association with
age was not linear and prevalence did not increase after middle age. The mean
density of infection decreased slightly with age. The association with the
density of the raccoon dog population leads to a tentative hypothesis that the
raccoon dog might be an important reservoir of sylvatic trichinellosis in
Finland.
PMID- 9639902
TI - Predictability of morphological gradients in the tapeworm, Hymenolepis diminuta.
AB - The strobila of an adult tapeworm represents a continual gradient of
developmental stages from immature to gravid proglottids. The purpose of this
study was to determine if organogenesis (as measured by the developmental
gradient) in tapeworms within a single host and among different hosts occurred at
the same rates. Rats were infected with Hymenolepis diminuta and the tapeworms
were recovered 20 days post-infection. The total number of proglottids in each
worm was determined, and five 'benchmarks' of organogenesis were quantified. The
data demonstrated that organogenesis in worms from a single host occurred at a
relatively constant rate, but that rates in tapeworms from different hosts were
different.
PMID- 9639903
TI - Experimental infection of larval Echinococcus multilocularis in the rodent brain
as a model for cerebral alveolar echinococcosis.
AB - Experimental infection of larval Echinococcus multilocularis in the rodent brain
was attempted to establish a murine model for cerebral alveolar echinococcosis.
Balb/c mice and jirds were injected intracranially with 10% of a homogenated
hydatid cyst mass. Small cystic larvae were observed macroscopically in the
cranial cavity 1, 2 and 5 months post-infection in both mice and jirds. Some
larval cysts from both rodents contained mature or immature protoscoleces. In
mice, the laminated layer was found in the lateral ventricle 2 months post
infection but without protoscoleces. At five months post-infection, larger larval
cysts were found in the cranial cavity of a mouse, which also demonstrated
partial palsy of the legs. A laminated layer with mature protoscoleces was
observed in the third ventricle and the mouse also harboured, in the left lung, a
larval cyst containing protoscoleces surrounded by lymphocytes. Jirds were also
found to be infected with metacestodes in the cranial cavity, but neither unusual
behaviour nor establishment of cysts inside the brain was observed in jirds
during the course of infection.
PMID- 9639905
TI - Different levels of Schistosoma mansoni infection induce changes in drug
metabolizing enzymes.
AB - Most carcinogens and xenobiotics are metabolized primarily by the mixed function
oxidase system which includes cytochrome P450, cytochrome b5, NADPH-cytochrome c
reductase and aryl hydrocarbon [benzo(a)pyrene] hydroxylase. The present study
investigates the influence of infection with different levels of Schistosoma
mansoni cercariae on the hepatic levels of reduced glutathione, glutathione S
transferase and glutathione reductase in addition to the enzymes of mixed
function oxidase. Cercariae infection levels of 60, 120, 180, 300 and 600 per
mouse increased: (i) the hepatic content of cytochrome P450 by 27%, 38%, 72%,
57%, 48% respectively; (ii) the aryl hydrocarbon hydroxylase activity by 44%,
64%, 76%, 90%, 51% respectively; and (iii) the hepatic level of reduced
glutathione by 67%, 83%, 103%, 60%, 38% respectively. The cytochrome b5 content
did not change at the lowest level of infection but increased at the other four
levels by 45%, 76%, 49% and 38% respectively. The activity of glutathione S
transferase increased at the first three levels by 42%, 40%, 27% respectively and
decreased at the last two levels by 28% and 52% respectively. On the other hand,
the activity of glutathione reductase did not change at any level, whereas, NADPH
cytochrome c reductase activity decreased at the last two levels by 44% and 54%.
The alterations in the activities of phase I & II of drug-metabolizing enzymes as
a result of infection with different levels of S. mansoni may thus change the
liver's capacity to detoxify many endogenous compounds and may also potentiate
the deleterious effects of aromatic hydrocarbons, e.g. benzo(a)pyrene, upon the
liver and probably other organs. Such alterations may also change the therapeutic
actions of drugs that are primarily metabolized by the P450 system, when
administered to patients with schistosomiasis.
PMID- 9639906
TI - Larval trematode infections in freshwater gastropods from the Albufera Natural
Park in Spain.
AB - Malacological samplings were made from January 1994 to December 1996 in the
Albufera Natural Park (Valencia, Spain) to trace the dynamics of molluscan
populations and the prevalence and intensity of infection by larval trematodes. A
total of 10,533 freshwater gastropods belonging to seven species (Lymnaea
auricularia, L. truncatula, L. palustris, L. peregra, Bithynia tentaculata, Physa
acuta and Gyraulus chinensis) was examined, and 110 (1.04%) were found to harbour
some of the nine distinguishable types of cercariae, namely four echinostome
cercariae (Hypoderaeum conoideum, Echinoparyphium recurvatum, Euparyphium
albuferensis, and Echinostoma sp.), four furcocercous cercariae, and one
xiphidiocercous cercaria. This study shows that the composition of the snail and
trematode communities may be determined by the particular environmental
conditions present and the human intervention in the area.
PMID- 9639907
TI - Histochemical glycogen and neutral lipid in Echinostoma trivolvis cercariae and
effects of exogenous glucose on cercarial longevity.
AB - Histochemical glycogen and neutral lipid studies were conducted on Echinostoma
trivolvis cercariae maintained in artificial spring water (ASW) at 24-25 degrees
C for up to 24 h after emergence from host snails. Treatment of whole cercariae
by the periodic acid Schiff (PAS) reagent with or without 1% malt diastase showed
that cercariae depleted glycogen mainly from the tail by 6 to 24 h postemergence.
The posterior tip of the tail remained PAS positive and diastase fast suggesting
the presence of mucopolysaccharides there. Fresh cercariae or those stained up to
24 h postemergence with Oil Red O showed the presence of neutral lipid droplets
in the excretory system. There was no discernible difference in the size,
abundance, or distribution of these droplets in fresh or aged cercariae.
Cercariae maintained in ASW plus 1% glucose for 12 or 23 h showed no evidence of
resynthesizing glycogen. Nevertheless, cercariae survived longer in 1% glucose
than in either 0.0, 0.1 or 0.5% glucose; but only at 23 h were any differences
statistically greater (one way ANOVA, P < 0.05).
PMID- 9639908
TI - Intestinal parasites of the grey fox (Pseudalopex culpaeus) in the central
Peruvian Andes.
AB - The intestines of 20 grey Peruvian foxes (Pseudalopex culpaeus) were examined for
the presence of Echinococcus granulosus and other intestinal parasites.
Echinococcus granulosus was not found in foxes but Taenia hydatigena and T.
multiceps were found in 7 and 4 animals respectively. The grey fox may not be a
suitable definitive host for E. granulosus. However, it may act as a sylvatic
reservoir of T. hydatigena and T. multiceps in the central Peruvian Andes.
PMID- 9639909
TI - Maintenance of Helisoma trivolvis naturally infected with Echinostoma trivolvis
in spring water at 4 degrees C for 300 days.
AB - Helisoma trivolvis (Pennsylvania strain) snails naturally infected with
Echinostoma trivolvis larvae were maintained for 10 months (300 days) at 4
degrees C in artificial spring water to determine the effects of storage on
parasite survival. Three of 20 snails were alive at 10 months and when isolated
in spring water at 22-24 degrees C released active cercariae. The mean number of
cercariae released in 2 h from each stored snail was significantly less than that
from freshly collected snails. Infectivity of cercariae from stored hosts to
experimentally infected, laboratory-raised Helisoma trivolvis (Colorado strain)
snails was significantly less than that of cercariae from fresh hosts based on
cyst recoveries in the Colorado strain of H. trivolvis within 24 h p.i. There was
no significant difference in the redial number or the number of cercariae per
redia in stored versus fresh snails. In conclusion, some reduction in cercarial
emergence and decrease in cercarial infectivity to a second intermediate snail
host occurred following storage of H. trivolvis naturally infected with E.
trivolvis in ASW at 4 degrees C for 10 months.
PMID- 9639910
TI - Photosensitizing drugs containing the benzophenone chromophore.
AB - The nonsteroidal anti-inflammatory agents ketoprofen, tiaprofenic acid, suprofen
and tolmetin, together with the anti-hyperlipoproteinemic drug fenofibrate and
the anti-arrhythmic amiodarone can be included in the group of benzophenone
derived photosensitizing drugs. They contain a diaryl ketone chromophore and
mediate the development of phototoxic reactions. In some cases, photoallergic
responses have been reported. These properties have been substantiated in
clinical reports, as well as by means of in vivo and in vitro assays. Tolmetin is
phototoxic in vitro, however there are no reports on photosensitization by this
drug in humans. In general, photochemical and photobiological studies strongly
suggest that photosensitization involves formal hydrogen abstraction (either in a
single step or via electron transfer followed by proton transfer) by the
benzophenone-like chromophore from the excited triplet state. In the case of
amiodarone, the radicals generated by photodehalogenation from the triplet are
responsible for the photosensitivity side-effects.
PMID- 9639911
TI - Photodynamic therapy as a tool for suppressing the haematogenous dissemination of
tumour cells.
AB - The chance of most cancer patients surviving their disease is to a high degree
dependent on the status of the metastatic processes. One general route of cancer
cell dissemination is passive transport in the blood stream, i.e., haematogenous
dissemination. In this study we try to find an answer to the following question:
is it possible to use photodynamic therapy for suppressing the haematogenous
dissemination of cancer cells? In first in vitro experiments we incubated CX1
cells (colon carcinoma cells) with two photosensitizers, Photofrin II and
mesotetra(hydroxyphenyl)chlorin (mTHPC). We added the cells to fresh whole blood
and irradiated the blood with suitable laser light in a flow-through irradiation
system. The tumour-cell survival fraction (SF) was determined with plating
efficiency. Using Photofrin II we observed a minimal tumour-cell survival in
blood of SF = 3.5% and using mTHPC we measured SF = 0.02%. These results
encourage further investigations concerning the use of photodynamic therapy for
suppressing haematogenous dissemination.
PMID- 9639912
TI - A robust, inexpensive filter for blocking UVC radiation in broad-spectrum 'UVB'
lamps.
AB - Accurate studies of the biological effects of UBV radiation require suitable
laboratory sources. Lamps labeled as UVB sources often emit UVC radiation that
contributes significantly to the levels of DNA damage. The UVC from an unfiltered
UVB source produced more pyrimidine dimers in soybean DNA than a lamp filtered by
a Pyrex dish that removes wavelengths of < 280 nm. Calculations based on action
spectra and on the emission spectra of unfiltered lamps indicate that UVC
contributes approximately 13%, 4% and approximately 1% of the total dimers
induced in unshielded cells or DNA, alfalfa cotyledons, and human skin,
respectively. Further, relative to a Pyrex dish-filtered lamp, an unfiltered lamp
would produce approximately 7-, 2.4- or 2.8-fold more dimers in these three
biological systems. We report here that a Pyrex dish provides an effective,
stable, robust and inexpensive filter for reducing or excluding the contribution
of UVC to damage induced by broad-spectrum 'UVB' lamps.
PMID- 9639913
TI - Raman spectroscopic study of microcosmic and photosensitive damage on the
liposomes of the mixed phospholipids sensitized by hypocrellin and its
derivatives.
AB - Using Raman spectroscopy, we studied and compared the characteristics of
microcosmic and photosensitive damage of the liposomes of mixed DPPE and DPPC
sensitized by hypocrellin and its derivatives at the molecular level. After
photosensitive damage, the structure of the liposomes of mixed phospholipids
changed considerably. The trans conformation decreased and gauche conformation
increased. The longitudinal order parameter in chains and the lateral order
parameter between chains decreased clearly. The results suggested that the
hydrocarbon chains of DPPE and DPPC were broken after the photodamage sensitized
by hypocrellin B (HB) and 5-Br-hypocrellin B (5-Br-HB). Photosensitive damage on
the liposomes sensitized by 5-Br-HB is stronger than that by hypocrellin A (HA)
and HB, that is, 5-Br-HB > HB > HA. The results elucidated the sites of
interaction or binding to HA, HB and 5-Br-HB in the liposomes and these changed
with the use of drugs.
PMID- 9639914
TI - Spatial measurement of oxygen levels during photodynamic therapy using time
resolved optical spectroscopy.
AB - Tissue oxygenation is one of the key dosimetric factors involved in the
application of photodynamic therapy (PDT). However, quantitative studies of
oxygenation levels at and surrounding the treatment site have been lacking both
before, during and after treatment. With the recent development of sensitive, non
invasive, optical spectroscopic techniques based on oxygen-dependent
phosphorescence quenching of probe compounds, oxygenation levels can now be
measured quantitatively at selected sites with spatial resolution on the
millimeter scale. We present results using the phosphorescent compound, palladium
meso-tetra(carboxyphenyl)porphine, for measurement of in vivo microvascular
oxygen tensions in rat liver during PDT. Time-resolved phosphorescence detection
was carried out using fibre-optic sensoring, and oxygen tensions were determined
from the phosphorescence lifetimes using Stern-Volmer analysis. During PDT
treatment using 5-aminolaevulinic (ALA) acid-induced protoporphyrin IX (PPIX)
with a 50 mg/kg ALA dose, oxygen levels near the irradiation fibre placed on the
surface of the liver showed a significant decrease by a factor of ten from 20 to
2 torr after an energy dose of 60 J using 100 mW at 635 nm. Areas farther from
the treatment site which were exposed to lower light doses exhibited lower
reductions in oxygen levels. This spectroscopic technique is a highly sensitive
means of investigating tissue oxygenation during and after treatment, and should
help not only to advance the understanding of hypoxia and microvascular damage in
the PDT mechanism but also contribute to improving the dosimetry of PDT.
PMID- 9639915
TI - Synergistic effect of UVB radiation and age on HMPS enzymes in rat lens
homogenate.
AB - The behaviour of rat lenticular enzymes, glucose-6-phosphate dehydrogenase (G6PD,
EC: 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGD, EC: 1.1.1.44) as a
function of age and UVB irradiation (in vitro) was investigated by irradiating
the lens homogenate from 3- and 12-month-old rats at 300 nm (100 microW cm-2). In
the 3-month-old group the specific activities of G6PD and 6PGD were reduced by
26% and 42%, respectively, after 24 h of irradiation, whereas in the 12-month-old
group the decrease was 38% and 49% respectively, which suggests that the
susceptibility of HMPS enzymes to UVB damage is higher in older lenses. The
decrease in specific activity was associated with a change in apparent K(m) and
Vmax (marginal in 3 months and significant in 12 months) of these enzymes due to
UVB irradiation. UVB irradiation also decreased the levels of NADPH and
NADPH/NADP ratio. These changes, altered activities of G6PD and 6PGD and altered
levels of NADPH, may in turn have a bearing on lens transparency.
PMID- 9639917
TI - Investigating biological response in the UVB as a function of ozone variation
using perturbation theory.
AB - In order to determine a biological response to ultraviolet radiation,
calculations of biologically weighted dose rates are required, which in turn
involve the integral over wavelength of an action spectrum multiplied by
appropriate surface flux data. To determine a biologically weighted dose rate
accurately, a reasonable wavelength resolution is required, involving a full
radiative transfer solution to be performed for each wavelength in order to
obtain the surface flux information. If biologically weighted dose rates are
needed as a function of ozone variation, then the number of radiative transfer
solutions quickly makes a large number of ozone variations cumbersome. This paper
shows that the perturbation theory developed for atmospheric radiative transfer
by Box and co-workers can predict surface fluxes and hence biologically weighted
dose rates for a large range of ozone variations very efficiently. The method is
then extended to calculate radiation amplification factors. Results for
biologically weighted dose rates are presented for a large range of solar zenith
angles and ozone loadings using perturbation theory and a full radiative transfer
code and show that the perturbation predictions never deviate very far from the
radiative transfer solutions.
PMID- 9639916
TI - Hemodynamic effects of 5-aminolevulinic acid in humans.
AB - Endogenous protoporphyrin IX (PpIX), which results from the oral administration
of 5-aminolevulinic acid (ALA), is being investigated for its efficacy as a
photosensitizing agent for photodynamic therapy (PDT). Clinical use of ALA has
been associated with only mild gastrointestinal side effects. The hemodynamic
effects of orally administered ALA in doses used for PDT are unknown. Six
patients with a significant history of cardiac disease underwent Swan-Ganz
catheterization prior to ALA administration and abdominal operation for PDT.
Hemodynamic data collection began at least 1 h prior to ALA, and continued for at
least 4 h subsequently, during which time no other medications were administered.
When compared to measurements made prior to ALA administration, all patients
displayed a significant decrease in systolic and diastolic blood pressures,
pulmonary artery systolic and diastolic pressures as well as pulmonary vascular
resistance. Five of the six patients also developed a decrease in systemic
vascular resistance. No significant changes in pulmonary capillary wedge
pressure, cardiac output or cardiac index was observed, but the mean pulse rate
rose significantly. These findings cannot be explained on the basis of other
cardiovascular depressants or to poor central volume status. Although no adverse
sequela were appreciated as a result of the observed hemodynamic changes, this
potential should be recognized in patients undergoing PDT using ALA.
PMID- 9639918
TI - Insertion mutagenesis of XpsD, an outer-membrane protein involved in
extracellular protein secretion in Xanthomonas campestris pv. campestris.
AB - XpsD is an outer-membrane protein required for extracellular protein secretion in
Xanthomonas campestris pv. campestris. Cross-linking and gelfiltration
chromatography analyses have suggested that it forms a multimer. To determine its
structure-function relationship, linker-insertion mutants were constructed in an
xpsD gene carried on a plasmid. To assay for secretion function, each mutant gene
was introduced into an xpsD::Tn5 mutant strain (XC1708) and assayed for alpha
amylase secretion on starch plates. To test whether the mutant genes exerted a
dominant-negative effect, each was introduced into the parental strain XC1701 and
examined for secretion interference. Nine functional, one semi-functional and
eleven non-functional mutants were obtained. All the non-functional mutants,
except two for which the mutant proteins were undetectable on immunoblots, showed
interference of normal secretion. The insertion sites in the different mutant
proteins are randomly distributed throughout the entire sequence of the XpsD
protein. All the permissive insertion sites are located where beta-turn or coiled
secondary structure is predicted. Over half of the non-permissive sites are
located within predicted helical or beta-sheet regions. By pretreating total
membranes of XC1701 in SDS at 50 degrees C, an immunoreactive band with high
molecular mass (HMM) could be detected that remained in the stacking gel during
SDS-PAGE. The semi-functional and all functional mutant proteins formed HMM
complexes that were as SDS-resistant as those of the wild-type, whereas all
except three of the non-functional mutant proteins formed HMM structures that
were less resistant to SDS than the wild-type. By analysing the appearance of SDS
resistant HMM complexes, we were able to detect conformational alterations in
XpsD that are too subtle to be detected by other assays.
PMID- 9639919
TI - Evidence for a role for the gumB and gumC gene products in the formation of
xanthan from its pentasaccharide repeating unit by Xanthomonas campestris.
AB - The biosynthesis of the extracellular polysaccharide xanthan in Xanthomonas
campestris pv. campestris is directed by a cluster of 12 genes, gumB-gumM.
Several xanthan-deficient mutants of the wild-type strain 8004 have previously
been described which carry Tn5 insertions in this region of the chromosome. Here
it is shown that the transposon insertion in one of these mutants, strain 8397,
is located 15 bp upstream of the translational start site of the gumB gene. EDTA
treated cells of strain 8397 were able to synthesize the lipid-linked
pentasaccharide repeating unit of xanthan from the three nucleotide sugar donors
(UDP-glucose, GDP-mannose and UDP-glucuronic acid) but were unable to polymerize
the pentasaccharide into mature xanthan. A subclone of the gum gene cluster
carrying gumB and gumC restored xanthan production to strain 8397 to levels
approximately 28% of the wild-type. In contrast, subclones carrying gumB or gumC
alone were not effective. These results are discussed with reference to previous
speculations, based on computer analysis, that gumB and gumC are both involved in
the translocation of xanthan across the bacterial membranes.
PMID- 9639920
TI - Cryptic carbapenem antibiotic production genes are widespread in Erwinia
carotovora: facile trans activation by the carR transcriptional regulator.
AB - Few strains of Erwinia carotovora subsp. carotovora (Ecc) make carbapenem
antibiotics. Strain GS101 makes the basic carbapenem molecule, 1-carbapen-2-em-3
carboxylic acid (Car). The production of this antibiotic has been shown to be
cell density dependent, requiring the accumulation of the small diffusible
molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) in the growth medium. When
the concentration of this inducer rises above a threshold level, OHHL is proposed
to interact with the transcriptional activator of the carbapenem cluster (CarR)
and induce carbapenem biosynthesis. The introduction of the GS101 carR gene into
an Ecc strain (SCRI 193) which is naturally carbapenem-negative resulted in the
production of Car. This suggested that strain SCRI 193 contained functional
cryptic carbapenem biosynthetic genes, but lacked a functional carR homologue.
The distribution of trans-activatable antibiotic genes was assayed in Erwinia
strains from a culture collection and was found to be common in a large
proportion of Ecc strains. Significantly, amongst the Ecc strains identified, a
larger proportion contained trans-activatable cryptic genes than produced
antibiotics constitutively. Southern hybridization of the chromosomal DNA of
cryptic Ecc strains confirmed the presence of both the car biosynthetic cluster
and the regulatory genes. Identification of homologues of the transcriptional
activator carR suggests that the cause of the silencing of the carbapenem
biosynthetic cluster in these strains is not the deletion of carR. In an attempt
to identify the cause of the silencing in the Ecc strain SCRI 193 the carR
homologue from this strain was cloned and sequenced. The SCRI 193 CarR homologue
was 94% identical to the GS101 CarR and contained 14 amino acid substitutions.
Both homologues could be expressed from their native promoters and ribosome
binding sites using an in vitro prokaryotic transcription and translation assay,
and when the SCRI 193 carR homologue was cloned in multicopy plasmids and
reintroduced into SCRI 193, antibiotic production was observed. This suggested
that the mutation causing the silencing of the biosynthetic cluster in SCRI 193
was leaky and the cryptic Car phenotype could be suppressed by multiple copies of
the apparently mutant transcriptional activator.
PMID- 9639921
TI - Yersinia pseudotuberculosis and Yersinia pestis are more resistant to
bactericidal cationic peptides than Yersinia enterocolitica.
AB - The action of bactericidal polycationic peptides was compared in Yersinia spp. by
testing peptide binding to live cells and changes in outer membrane (OM)
morphology and permeability. Moreover, polycation interaction with LPS was
studied by measuring the dependence of dansylcadaverine displacement and zeta
potential on polycation concentration. When growth at 37 degrees C, Yersinia
pestis and Yersinia pseudotuberculosis bound less polymyxin B (PMB) than
pathogenic or non-pathogenic Yersinia enterocolitica, regardless of virulence
plasmid expression. Y. pseudotuberculosis OMs were unharmed by PMB concentrations
causing extensive OM blebbing in Y. enterocolitica. The permeability to lysozyme
caused by PMB was greater in Y. enterocolitica than in Y. pseudotuberculosis or
Y. pestis and differences increased at 37 degrees C. Similar observations were
made with other polycations using a polymyxin/novobiocin permeability assay. With
LPS of cells grown at 26 degrees C, polycation binding was highest for Y.
pseudotuberculosis and lowest for Y. pestis, with Y. enterocolitica yielding
intermediate results which were lower for pathogenic than for non-pathogenic
strains. With LPS of cells grown at 37 degrees C, polycation binding remained
unchanged for Y. pestis and pathogenic Y. enterocolitica, increased for non
pathogenic Y. enterocolitica and decreased for Y. pseudotuberculosis to Y. pestis
levels. Polycation binding related in part to differences in charge density (zeta
potential) of LPS aggregates, suggesting similar effects at bacterial surfaces.
It is suggested that species and temperature differences in polycation resistance
relate to infection route, invasiveness and intracellular multiplication of
Yersinia spp.
PMID- 9639922
TI - Yersinia pseudotuberculosis and Yersinia pestis show increased outer membrane
permeability to hydrophobic agents which correlates with lipopolysaccharide acyl
chain fluidity.
AB - The hydrophobic probe N-phenyl-1-naphthylamine accumulated less in non-pathogenic
Yersinia spp. and non-pathogenic and pathogenic Yersinia enterocolitica than in
Yersinia pseudotuberculosis or Yersinia pestis. This was largely due to
differences in the activity of efflux systems, but also to differences in outer
membrane permeability because uptake of the probe in KCN/arsenate-poisoned cells
was slower in the former group than in Y. pseudotuberculosis and Y. pestis. The
probe accumulation rate was higher in Y. pseudotuberculosis and Y. pestis grown
at 37 degrees C than at 26 degrees C and was always highest in Y. pestis. These
yersiniae had LPSs with shorter polysaccharides than Y. enterocolitica,
particularly when grown at 37 degrees C. Gel<-->liquid-crystalline phase
transitions (Tc 28-31 degrees C) were observed in LPS aggregates of Y.
enterocolitica grown at 26 and 37 degrees C, with no differences between non
pathogenic and pathogenic strains. Y. pseudotuberculosis and Y. pestis LPSs
showed no phase transitions and, although the fluidity of LPSs of Y.
pseudotuberculosis and Y. enterocolitica grown at 26 degrees C were close below
the Tc of the latter, they were always in a more fluid state than Y.
enterocolitica LPS. Comparison with previous studies of Salmonella choleraesuis
subsp. choleraesuis serotype minnesota rough LPS showed that the increased
fluidity and absence of transition of Y. pseudotuberculosis and Y. pestis LPSs
cannot be explained by their shorter polysaccharides and suggested differences at
the lipid A/core level. It is proposed that differences in LPS-LPS interactions
and efflux activity explain the above observations and reflect the adaptation of
Yersinia spp. to different habitats.
PMID- 9639923
TI - Lipopolysaccharide expression within the genus Bordetella: influence of
temperature and phase variation.
AB - LPSs play an important role in bacterial pathogenesis. In this study, the LPS
expression of the seven known Bordetella species and its dependency on growth
temperature was analysed by oxidative silver staining of proteinase-K-treated
whole bacteria separated by Tricine-SDS-PAGE. The bordetellae were found to have
extensively variable LPS in a species-specific way. In addition, the human and
ovine Bordetella parapertussis strains exhibited host-specific LPS expression.
LPSs from human B. parapertussis strains grown at 37 and 25 degrees C were
distinct. Growth temperature also affected LPS production by several Bordetella
bronchiseptica strains. In some of these cases, BvgAS, the global regulator of
virulence factors, was involved in this regulation of LPS biosynthesis. In
contrast, no evidence was found for the involvement of the Bordetella pertussis
BvgAS system in regulation of LPS synthesis. The obligate human pathogens B.
pertussis and Bordetella holmesii are closely related but were shown to produce
immunologically distinct LPSs. These species are isolated from the upper
respiratory tract and blood, respectively. This raises several interesting
questions concerning the potential role of LPS as a virulence factor in the
infection processes.
PMID- 9639924
TI - Characterization of the glnB gene product of Nostoc punctiforme strain ATCC
29133: glnB or the PII protein may be essential.
AB - Bacterial PII proteins, encoded by glnB genes, are central signalling molecules
in nitrogen regulatory pathways and are modulated by post-translational
modification in response to the cellular nitrogen status. The glnB gene was
cloned from the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme
strain ATCC 29133 (PCC 73102) by heterologous hybridization to a Synechococcus
sp. strain PCC 7942 gene fragment. Expression of the cloned gene was verified by
hybridization to N. punctiforme total RNA and a single cross-reactive polypeptide
was observed in immunoblots of N. punctiforme extracts probed with anti
Synechococcus 7942 PII antiserum. Modification of the purified N. punctiforme PII
protein by a Synechococcus 7942 PII kinase was observed, but modified forms of
PII were not detected in extracts of N. punctiforme from a variety of incubation
conditions. The N. punctiforme glnB gene could not be disrupted by targeted gene
replacement unless a second copy of glnB was provided in trans, suggesting that
the gene or gene product is essential for growth under the conditions tested.
PMID- 9639925
TI - Multiple oligomeric forms of glucose-6-phosphate dehydrogenase in cyanobacteria
and the role of OpcA in the assembly process.
AB - Multiple molecular forms of glucose-6-phosphate dehydrogenase (G6PDH) were
detected by activity staining in non-denaturing polyacrylamide gels of cell-free
extracts from a range of cyanobacteria including Anabaena sp. PCC 7120,
Synechococcus sp. PCC 7942, Plectonema boryanum PCC 73110, Synechocystis sp. PCC
6803, Nostoc sp. MAC PCC 8009 and the marine strain Synechococcus sp. WH7803. In
most of the species tested, the profile of G6PDH activities was modulated by the
growth of the cells in the presence of exogenous 10 mM glucose. Using an
antiserum raised against a fragment of G6PDH from Anabaena sp. PCC 7120, it was
shown that the different molecular forms of G6PDH all contained an antigenically
related subunit, suggesting that the different forms arose from different
quaternary structures involving the same monomer. An insertion mutant of
Synechococcus sp. PCC 7942 was constructed in which the opcA gene, adjacent to
zwf (encoding G6PDH), was disrupted. Although no reduction in the amount of G6PDH
monomers (Zwf) was observed in the opcA mutant, activity staining of native gels
indicated that most of this protein is not assembled into one of the active
oligomeric forms. The oligomerization of G6PDH in extracts of the opcA mutant was
stimulated in vitro by a factor present in crude extracts of the wild-type,
suggesting that the product of the opcA gene is involved in the oligomerization
and activation of G6PDH.
PMID- 9639926
TI - Pleiotropic effects of potassium deficiency in a heterocystous, nitrogen-fixing
cyanobacterium, Anabaena torulosa.
AB - Omission of potassium from the growth medium caused multiple metabolic
impairments and resulted in cessation of growth of the filamentous,
heterocystous, nitrogen-fixing cyanobacterium Anabaena torulosa, during both
diazotrophic and nitrogen-supplemented growth. Prominent defects observed during
potassium deprivation were: (i) the loss of photosynthetic pigments, (ii)
impairment of photosynthetic functions, (iii) reduced synthesis of dinitrogenase
reductase (Fe-protein), (iv) inhibition of nitrogenase activity, and (v) specific
qualitative modifications of protein synthesis leading to the repression of
twelve polypeptides and synthesis and accumulation of nine novel polypeptides.
The observed metabolic defects were reversible, and growth arrested under
prolonged potassium deficiency was fully restored upon re-addition of potassium.
Such pleiotropic effects of potassium deficiency demonstrate that apart from its
well-known requirement for pH and turgor homeostasis, K+ plays other vital
specific roles in cyanobacterial growth and metabolism.
PMID- 9639927
TI - Phytase activity of anaerobic ruminal bacteria.
AB - Phytase catalyses the release of phosphate from phytate (myo-inositol
hexakisphosphate), the predominant form of phosphorus in cereal grains, oilseeds
and legumes. The presence of phytase activity was investigated in 334 strains of
22 species of obligately anaerobic ruminal bacteria. Measurable activities were
demonstrated in strains of Selenomonas ruminantium, Megasphaera elsdenii,
Prevotella ruminicola, Mitsuokella multiacidus and Treponema spp. Strains
isolated from fermentations with cereal grains proved to have high activity, and
activity was particularly prevalent in S. ruminantium, with over 96% of the
tested strains being positive. The measured phytase activity was found
exclusively associated with the bacterial cells and was produced in the presence
of approximately 14 mM phosphate. The most highly active strains were all S.
ruminantium, with the exception of the one Mitsuokella multiacidus strain
examined. Phytase activity varied greatly among positive strains but activities
as high as 703 nmol phosphate released (ml culture)-1 were measured for a S.
ruminantium strain and 387 nmol phosphate released (ml culture)-1 for the
Mitsuokella multiacidus strain.
PMID- 9639928
TI - Inducible chitinolytic system of Aspergillus fumigatus.
AB - Incubation of Aspergillus fumigatus NCPF 2140 in growth medium containing 1%
chitin as sole carbon source led to induction of specific extracellular
chitinolytic activity of 1.5 mumol GlcNAc released min-1 (mg protein)-1. The
effect was repressed by the inclusion of GlcNAc in the medium, indicating
regulation by a negative feedback mechanism. Extracellular chitinase activity was
inhibited by allosamidin (IC50 0.12 microM). Multiple chitinolytic enzymes were
detected on zymograms of extracellular preparations; levels of individual enzymes
induced were dependent upon whether cells were incubated with purified colloidal
chitin or a crude preparation of crystalline chitin. A major, inducible, 45 kDa
chitinase was purified using ammonium sulphate precipitation, chitin affinity
chromatography and a novel procedure involving the electroelution of the enzyme
from a substrate gel containing glycol chitin. The enzyme is a glycoprotein with
endochitinase activity.
PMID- 9639929
TI - Characterization of a second cell-associated Arg-specific cysteine proteinase of
Porphyromonas gingivalis and identification of an adhesin-binding motif involved
in association of the prtR and prtK proteinases and adhesins into large
complexes.
AB - Porphyromonas gingivalis has been associated with the development of adult
periodontitis and cysteine proteinases with Arg- and Lys-specific activity have
been implicated as major virulence factors. In a cell sonicate of P. gingivalis
W50, a complex of non-covalently associated proteins has been previously
characterized. This complex is composed of a 45 kDa Arg-specific, calcium
stabilized cysteine proteinase (PrtR45), a 48 kDa Lys-specific cysteine
proteinase (PrtK48) and seven sequence-related adhesins designated PrtR44,
PrtR15, PrtR17, PrtR27, PrtK39, PrtK15 and PrtK44, with all proteins being
encoded by the two genes prtR and prtK. It has been proposed that these non
covalently associated complexes form extracellularly after autolytic processing
of the PrtR and PrtK polyproteins, with the adhesins binding to the proteinases
(PrtR45 and PrtK48) and autoaggregating. Another form of the cell-associated, Arg
specific, calcium-stabilized cysteine proteinase is described here. Designated
PrtRII50, it is a discrete 50 kDa protein with no adhesin-association and has
enzymic characteristics and an inhibitor/activator profile almost identical to
PrtR45. The PrtRII50 proteinase is encoded as a preproprotein by a second gene,
prtRII, with high sequence similarity to PrtR except that it lacks the C-terminal
adhesin domains. A comparison of the deduced amino acid sequence of PrtRII50 with
that of the adhesin-associated proteinases PrtR45 and PrtK48 revealed that
PrtRII50 does not contain a C-terminal motif that is conserved in PrtR45 and
PrtK48. Related motifs are also found in the adhesin domains of PrtR and PrtK. It
is proposed that this conserved motif is an adhesin-binding motif (ABM) involved
in association of the PrtR and PrtK proteinases and adhesins into large
complexes, as the PrtR-PrtK proteinase-adhesin complex inactivated by N-alpha-p
tosyl-L-lysine chloromethyl ketone (TLCK) was shown to bind specifically to a
synthetic peptide corresponding to the conserved motif in a competitive binding
assay.
PMID- 9639930
TI - The yvsA-yvqA (293 degrees-289 degrees) region of the Bacillus subtilis
chromosome containing genes involved in metal ion uptake and a putative sigma
factor.
AB - The region between yvsA (293 degrees) and yvqA (289 degrees) of the Bacillus
subtilis chromosome has been sequenced within the framework of the B. subtilis
168 international sequencing programme. A primary analysis of the 42 ORFs
identified in this 43 kb region is presented. The region included a high
proportion of genes that did not show homology with genes in other bacteria. The
identified ORFs showed homology to proteins involved in the transport of metal
ions, two-component signal transducers, ATP-binding-cassette-type transporters
and a sigma factor.
PMID- 9639931
TI - Psychroflexus torquis gen. nov., sp. nov., a psychrophilic species from Antarctic
sea ice, and reclassification of Flavobacterium gondwanense (Dobson et al. 1993)
as Psychroflexus gondwanense gen. nov., comb. nov.
AB - A group of sea-ice-derived psychrophilic bacterial strains possessing the unusual
ability to synthesize the polyunsaturated fatty acids eicosapentaenoic acid (20:5
omega 3) and arachidonic acid (20:4 omega 6) belong to the Family
Flavobacteriaceae (Flexibacter-Bacteroides-Flavobacterium phylum), according to
16S rRNA sequence analysis. Surprisingly, the isolates were also found to cluster
closely to the moderately halophilic and psychrotrophic species [Flavobacterium]
gondwanense (sequence similarity 97.8-98.1%). The whole-cell fatty acid profiles
of this group and [Flavobacterium] gondwanense were very similar and distinct
from other related flavobacteria. The sea ice strains and [Flavobacterium]
gondwanense differed substantially in terms of ecophysiology, possibly
representing divergent adaptations to sympagic and planktonic marine habitats,
respectively. Evidence based on phylogeny and fatty acid profiles supports the
conclusion that the taxa are close relatives distinct from other bacterial
groups. It is thus proposed that the sea ice strains represent a novel taxon
designated Psychroflexus torquis gen. nov., sp. nov. (type strain ACAM 623T)
while [Flavobacterium] gondwanense becomes Psychroflexus gondwanense gen. nov.,
comb. nov.
PMID- 9639932
TI - PAGE analysis of the heteroduplexes formed between PCR-amplified 16S rRNA genes:
estimation of sequence similarity and rDNA complexity.
AB - Analysis of the 16S rRNA genes retrieved directly from different environments has
proven to be a powerful tool that has greatly expanded our knowledge of microbial
diversity and phylogeny. It is shown here that sequence similarity between 80 and
100% among 16S rDNAs can be estimated by the electrophoretic migration of their
heteroduplexes. This was measured by hybridization and electrophoresis in
polyacrylamide gels of the product obtained after PCR amplification of almost the
entire 16S rRNA gene from different bacterial species. These heteroduplexes were
also observed after amplification of samples containing DNA from two or more
bacterial species and a procedure was applied to identify reliably heteroduplexes
among the amplification products. The electrophoretic migration of the
heteroduplexes observed after PCR was used to detect the presence of 16S rDNAs
with different sequences in DNA extracted from both a mixture of two bacterial
species and samples containing a natural bacterial community.
PMID- 9639933
TI - Identification of Mycobacterium tuberculosis signal sequences that direct the
export of a leaderless beta-lactamase gene product in Escherichia coli.
AB - Proteins secreted by Mycobacterium tuberculosis may play a key role in virulence
and may also constitute antigens that elicit the host immune response. However,
the M. tuberculosis protein export machinery has not been characterized. A
library of M. tuberculosis H37Rv genomic DNA fragments ligated into a signal
sequence selection vector that contained a leaderless beta-lactamase gene and an
upstream Tac promoter was constructed. Transformation of Escherichia coli with
the M. tuberculosis DNA library and selection on plates containing 50-100
micrograms ampicillin ml-1 resulted in the identification of 15 Ampr clones out
of a total of 14,000 transformants. Twelve of the beta-lactamase gene fusions
conferred high levels of Ampr (up to 1 mg ampicillin ml-1); insert sizes ranged
from 350 to 3000 bp. Of ten inserts that were completely sequenced, two were
identified as fragments of the genes for M. tuberculosis antigens 85A and 85C,
which are the major secreted proteins of this pathogen. Seven of the remaining
inserts were > or = 97% identical to hypothetical ORFs in the M. tuberculosis
genome, one of which encoded a protein with 35% identity to a low-affinity
penicillin-binding protein (PBP) from Streptomyces clavuligerus. Four of the
seven hypothetical ORFs encoded putative exported proteins with one or more
membrane interaction elements, including lipoprotein attachment sites and type I
and II transmembrane (TM) segments. All of the inserts encoded typical signal
sequences, with the exception of a possible type II membrane protein. It is
concluded that expression of beta-lactamase gene fusions in E. coli provides a
useful system for the identification and analysis of M. tuberculosis signal
sequence-encoding genes.
PMID- 9639934
TI - Genes for D-arabinitol and ribitol catabolism from Klebsiella pneumoniae.
AB - The enzymes for catabolism of the pentitols D-arabinitol (Dal) and ribitol (Rbt)
and the corresponding genes from Klebsiella pneumoniae (dal and rbt) and
Escherichia coli (atl and rtl) have been used intensively in experimental
evolutionary studies. Four dal and four rbt genes from the chromosome of K.
pneumoniae 1033-5P14 were cloned and sequenced. These genes are clustered in two
adjacent but divergently transcribed operons and separated by two convergently
transcribed repressor genes, dalR and rbtR. Each operon encodes an NAD-dependent
pentose dehydrogenase (dalD and rbtD), and ATP-dependent pentulose kinase (dalK
and rbtK) and a pentose-specific ion symporter (dalT and rbtT). Although the
biochemical reactions which they catalyse are highly similar, the enzymes showed
interesting deviations. Thus, DalR (313 aa) and RbtR (270 aa) belong to different
repressor families, and DalD (455 aa) and RbtD (248 aa), which are active as a
monomer or as tetramers, respectively, belong to different dehydrogenase
families. Of the two kinases (19.3% identity), DalK (487 aa) belongs to the
subfamily of short D-xylulokinases and RbtK (D-ribulokinase; 535 aa) to the
subfamily of long kinases. The repressor, dehydrogenase and kinase genes did not
show extensive similarity beyond local motifs. This contrasts with the ion
symporters (86.6% identity) and their genes (82.7% identity). Due to their
unusually high similarity, parts of dalT and rbtT have previously been claimed
erroneously to correspond to 'inverted repeats' and possible remnants of a
'metabolic transposon' comprising the dal and rbt genes. Other characteristic
structures, e.g. a secondary att lambda site and chi-like sites, as well as the
conservation of this gene group in E. coli C are also discussed.
PMID- 9639935
TI - Molecular analysis of the DNA gyrB gene from Myxococcus xanthus.
AB - DNA gyrase, an essential type II topoisomerase, mediates negative supercoiling of
the bacterial chromosome, thereby affecting the processes of DNA replication,
transcription, recombination and repair. The gyrB gene from the Gram-negative
soil bacterium Myxococcus xanthus was sequenced. The sequence predicts a protein
of 815 amino acid residues displaying significant homology to all known GyrB
proteins. A 6-His-GyrB fusion protein was overexpressed in Escherichia coli and
purified to near homogeneity using affinity chromatography on Ni-nitrilotriacetic
acid-agarose and novobiocin-Sepharose columns. The fusion protein bound
novobiocin and cross-reacted with anti-E. coli GyrB antibodies, indicating
structural and functional similarities to the E. coli DNA GyrB. The gene was
mapped to the region of the origin of replication (oriC) of M. xanthus.
PMID- 9639936
TI - The NADH-dependent glutamate dehydrogenase enzyme of Bacteroides fragilis Bf1 is
induced by peptides in the growth medium.
AB - Bacteroides fragilis Bf1 possesses two enzymes having glutamate dehydrogenase
(GDH) activity. One is dual cofactor NAD(P)H-dependent, while the other has NADH
specific activity. The gene encoding the NADH-GDH (gdhB) was cloned by
complementation of the glutamate auxotrophic mutant Escherichia coli MX3004 and
the recombinant protein was characterized with respect to the GDH activities
present in the parental organism grown under different nitrogen conditions. The
NAD(P)H-dependent GDH of B. fragilis was confirmed to be most active under high
ammonia conditions, but the NADH-specific GDH levels were increased by high
peptide concentrations in the growth medium and not regulated by the levels of
ammonia. Northern blotting analysis showed that gdhB regulation was at the
transcription level, with a single transcript of approximately 1.6 kb being
produced. GDH activity was demonstrated by zymography of the parental and
recombinant enzymes. The recombinant GDH was NADH-specific and co-migrated with
the equivalent enzyme band from B. fragilis cell extracts. The gdhB structural
gene comprises 1335 bp and encodes a protein of 445 aa (49 kDa). Comparisons of
the derived protein sequence with that of GDH from other bacteria indicated that
significant sequence homology and conservation of functional domains exists with
enzymes of Family I-type hexameric GDH proteins.
PMID- 9639937
TI - Cyanide hydrolysis in a cyanide-degrading bacterium, Pseudomonas stutzeri AK61,
by cyanidase.
AB - The cyanide-degrading bacterial strain AK61 was isolated from waste water at a
metal-plating plant. The isolated strain was characterized by Gram-staining,
quinone analysis, fatty acid profile and the API 20NE identification system, and
identified as Pseudomonas stutzeri. Whole cells were able to degrade cyanide
rapidly in a 1 mM solution containing no organic substances, and produced ammonia
as a product. The induction of the cyanide-degrading activity of P. stutzeri AK61
did not depend on the presence of cyanide in the culture medium during growth.
The cyanide-degrading enzyme was purified approximately 49-fold from a cell
extract of P. stutzeri AK61. The enzyme had a K(m) of 1.7 mM for cyanide and a
specific activity of 54.6 mumol ammonia produced min-1. The activity of the
enzyme was optimal at 30 degrees C and pH 7.5. The results of SDS-PAGE, gel
filtration chromatography and NH2-terminal amino acid sequence analysis of the
enzyme indicated that the functional enzyme was an aggregated protein consisting
of a 38 kDa polypeptide. Like cyanidase (cyanide dihydratase), it was shown that
the enzyme catalysed the hydrolysis of cyanide to ammonia and formate.
PMID- 9639938
TI - Distribution of 14C-labelled carbon from glucose and glutamate during anaerobic
growth of Saccharomyces cerevisiae.
AB - The distribution of carbon from glucose and glutamate was studied using
anaerobically grown Saccharomyces cerevisiae. The yeast was grown on glucose (20
g l-1) as the carbon/energy source and glutamic acid (3.5 g l-1) as additional
carbon and sole nitrogen source. The products formed were identified using
labelled [U-14C]glucose or [U-14C]glutamic acid. A seldom-reported metabolite in
S. cerevisiae, 2-hydroxyglutarate, was found in significant amounts. It is
suggested that 2-hydroxyglutarate is formed from the reduction of 2-oxoglutarate
in a reaction catalysed by a dehydrogenase. Succinate, 2-oxoglutarate and 2
hydroxyglutarate were found to be derived exclusively from glutamate. Based on
radioactivity measurements, 55%, 17% and 14% of the labelled glutamate was
converted to 2-oxoglutarate, succinate and 2-hydroxyglutarate, respectively, and
55%, 9% and 3% of the labelled glucose was converted to ethanol, glycerol and
pyruvate, respectively. No labelled glucose was converted to 2-oxoglutarate,
succinate or 2-hydroxyglutarate. Furthermore, very little of the evolved CO2 was
derived from glutamate. Separation of the amino acids from biomass by paper
chromatography revealed that the glutamate family of amino acids (glutamic acid,
glutamine, proline, arginine and lysine) originated almost exclusively from the
carbon skeleton of glutamic acid. It can be concluded that the carbon flow
follows two separate paths, and that the only major reactions utilized in the
tricarboxylic acid (TCA) cycle are those reactions involved in the conversion of
2-oxoglutarate to succinate.
PMID- 9639939
TI - A novel quantitative mating assay for the fungal pathogen Cryptococcus neoformans
provides insight into signalling pathways responding to nutrients and
temperature.
AB - Cryptococcus neoformans is a fungal pathogen that causes a lethal meningitis in
immunocompromised individuals. Several factors are associated with virulence of
this fungus, including its mating type; however, the mechanism by which mating
type affects virulence is unknown. C. neoformans is a basidiomycete that exists
in two mating types called a and alpha that can fuse to form an a/alpha dikaryon.
A mating assay was developed that allowed a quantitative analysis of cryptococcal
mating physiology. Interestingly, the efficiency of mating appeared to be
dependent on temperature, being highest at 30 degrees C and almost completely
absent at 37 degrees C. Thus, while mating type itself may be associated with
virulence (which must occur at 37 degrees C), the ability to mate is probably not
a virulence factor. Mating efficiency was increased by altering the carbon or
nitrogen sources to give so-called starvation media. The addition of various
drugs also seemed to alter the frequency of mating, depending on the composition
of mating medium. The data suggested that cAMP, 8-bromo-cAMP and caffeine
increased mating on starvation medium but only cAMP and 8-bromo-cAMP stimulated
mating on rich medium; caffeine was unable to stimulate mating on rich medium.
Aluminium fluoride, an activator of heterotrimeric GTP-binding proteins (G
proteins), was also found to stimulate mating, suggesting the involvement of a G
protein that may regulate the level of cAMP.
PMID- 9639940
TI - Effects of relative humidity and applied force on atomic force microscopy images
of the filamentous phage fd.
AB - The filamentous phage fd was studied by both contact- and tapping-mode atomic
force microscopy under conditions of controlled variations in relative humidity
and changes in the applied tip force. By spin-coating freshly cleaved mica with
phage containing solutions having very low salt content followed by rapid
humidity control, stable and reliable sample preparation was achieved. The
apparent height of the phage varied by about 10-fold with a quadratic dependence
on the stabilized relative humidity, extrapolating to 73% of the accepted X-ray
diffraction-based height at 0% relative humidity. The variation in measured
height with relative humidity largely reconciles previous widely varying atomic
force microscopy estimates of this dimension for the filamentous phage. Our
finding that contact-mode images of phage are more difficult to analyze than
those acquired in tapping mode are consistent with previously published results
on other biological specimens such as DNA.
PMID- 9639941
TI - Reconstruction of symmetry deviations: a procedure to analyze partially decorated
F-actin and other incomplete structures.
AB - The absolute value of individual differences (AVID) procedure is a method to map
variations within images arising from deviations in symmetry. We devised this
procedure to analyze images of actin filaments decorated with actin-binding
proteins (ABPs). In three-dimensional maps of such actin complexes, ABPs often
appear weak (i.e. they have low density) relative to actin. Because the 3D map
represents an average taken over equivalent positions in the helix, the final
density at the position of the ABP represents an average of the densities at all
ABP sites. If there is either incomplete binding or a conformational variability
of the bound ABP, the average density will be lowered. By the same argument, the
variation of density at these sites will be increased. The aim of the AVID
procedure is to calculate the density variations within partially decorated
filaments and thereby attempt to locate the bound protein. We tested the AVID
procedure with model data and then applied it to electron micrographs of F-actin
decorated with an actin-binding domain of fimbrin known as N375 [Hanein et al.,
J. Cell Biol. 139 (1997) 387-396]. The AVID maps have peaks at the site where
N375 binds. Because it excludes the layer line data, the AVID procedure uses data
that are independent of the data used for 3D reconstruction and difference
mapping. It therefore provides an independent way to localize the bound subunit
without the need for a map of undecorated actin. Moreover, the difficulties of
scaling maps are minimized. This procedure could also be applied to structures
with non-helical symmetry.
PMID- 9639942
TI - Calcium antagonists, is there a real concern about safety?
AB - Calcium antagonists are widely used in the treatment of arterial hypertension
and, or in ischemic heart disease. During the last 3 years, controversial
articles and editorials have been published concerning the potential risk of
calcium antagonists in regard to mortality, cancer and haemorrhage. The
information has been mainly derived from case-control studies. The major concern
about such observational studies of treatment outcome is the large potential for
systematic error to affect the results. However, overviews of controlled trials
with calcium antagonists do not provide clear evidence of an effect of calcium
antagonists on mortality, risk of cancer and risk of bleeding.
PMID- 9639943
TI - Immunotherapy for allergic reactions.
AB - In this review, hyposensitization or immunotherapy will be discussed. The
earliest immunotherapy was applicated in allergic respiratory diseases such as
asthma and rhinitis. The most important indication has become the treatment of
hymenoptera allergy. Some less frequently indications are associated with drug
allergy. Immunotherapy is most frequently indicated in IgE mediated diseases, but
new applications for cell mediated reactions will be described. With the
introduction of molecular biology in allergology new theoretical possibilities
emerged: use of peptide antigens, recombinant allergens, anticytokines....
Unfortunately, these newer approaches did not (yet) cause a breakthrough. The
cost of these products will be a major draw back, even when ethical problems for
using them on a larger scale will have been solved.
PMID- 9639944
TI - Epidemiology as a tool for hospital infection control.
AB - Epidemiology today studies the occurrence of health and disease and evaluates the
global quality of health care, whereas it previously mainly consisted in the
investigation of infectious outbreaks. This paper describes basic principles of
descriptive and analytical hospital epidemiology, and focuses on the standardized
and professional methodology used to manage nosocomial outbreaks. The basis for
applied epidemiology for infection control purposes is surveillance. Computer
technology permits data retrieval for detailed investigation by filtering the
microbiology reports for specific data with nosocomial and epidemiological
importance, so that expertise and organization of the microbiology laboratory
have become key success factors for surveillance. In Belgium epidemiologists
rarely, if ever, practice in hospitals as a separate discipline, although
professional hospital epidemiology as part of infection control would be
profitable for all. A debate is still to be held on how epidemiology should be
organized in Belgian hospitals. It is generally accepted and provided by law that
hospital hygiene physicians and nurses should perform epidemiological
investigations and surveillance. However, the lack of professional training in
epidemiology and insufficient resources constitute two major drawbacks.
Microbiological typing techniques have become indispensable tools for
epidemiology and should be accessible to every hospital infection control
practitioner.
PMID- 9639945
TI - [Inflammation phenomena in vasculitis: from immune complexes to less immune
forms].
AB - Immune complexes are involved in the pathogenesis of Henoch-Schonlein purpura,
essential mixed cryoglobulinemia, hepatitis B-associated periarteritis nodosa and
hypersensitivity vasculitis (related to infection or medications). ANCA's
probably play a pathogenic role in Wegener's Granulomatosis, microscopic
polyangiitis and renal-limited vasculitis. Pathologic responses of T-lymfocytes
and granuloma formation have been demonstrated in temporal arteritis, Takayasu
arteritis, Wegener's Granulomatosis, Churg-Strauss syndrome and Kawasaki
syndrome. The eventual pathogenic role of AECA's is less clear, with the possible
exception of rheumatoid arthritis and systemic lupus erythematosus. These four
pathogenic factors are not mutually exclusive: several mechanisms may play in one
disorder, as has been demonstrated for Wegener's Granulomatosis. From these new
insights in the pathogenesis of vasculitis, new therapies with better efficacy
and fewer side effects may arise.
PMID- 9639946
TI - Neurological complications in critically ill patients; septic encephalopathy,
critical illness polyneuropathy.
AB - Septic encephalopathy and critical illness polyneuropathy are two syndromes,
appearing at different stages in critically ill patients. Their aetiology is
unclear, but many arguments seem to associate them with respiratory insufficiency
in a context of systemic inflammatory response syndrome (S.I.R.S.) and multiple
organ dysfunction syndrome (M.O.D.S.). Septic encephalopathy appears early in the
course of sepsis, diagnosis is based on clinical picture and electro
encephalogram. The exact pathogenesis is unclear. Prognosis is related to the
underlying pathology, and treatment is supportive. Critical illness
polyneuropathy is a predominantly motor axonal dysfunction, occurring in a
setting of respiratory insufficiency, S.I.R.S., and M.O.D.S. A weaning problem
often indicates the presence of critical illness polyneuropathy. Diagnosis is
made on history, clinical picture and electromyographic studies. Indeed, motor
and sensory conduction studies show a reduction of the amplitude of action
potentials. In a later stage fibrillations and positive sharp waves emerge, with
a further reduction of action potentials. Follow-up examinations reveal signs of
axonal regeneration. The exact aetiology is unknown, but may be related to sepsis
and M.O.D.S. Sepsis and M.O.D.S. are associated with the release of "mediator"
substances, and somewhere in this cascade, there might be a toxin, influencing
the nerve. A differential diagnosis with myopathy and neuromuscular transmission
defects has to be made. Specific treatment is absent, and prognosis is related to
the underlying pathology.
PMID- 9639947
TI - The wide and deep excision of primary malignant melanoma: a dogma on the decline.
AB - For years, a wide and deep excision of primary cutaneous melanomas has been
recommended to achieve a better care and to decrease the risk of local recurrence
of the disease. However, recent studies indicate that removal of peritumoral
tissue beyond complete excision of the primary neoplasm does not decrease
significantly the risk of local metastases. In addition, it confers no benefit to
the patient survival.
PMID- 9639948
TI - GB virus C: a novel pathogen or a curiosity for virologists?
AB - The recently identified GB virus C is a flavivirus related to the hepatitis C
virus. It appears quite prevalent in the general population and especially in
individuals at risk of parenteral transmission. Many questions remain, most
importantly the pathogenic role of the virus. It is unlikely that this virus has
a major role in hepatic disease.
PMID- 9639949
TI - [Nasal CPAP in sleep-related respiration disorders: patient profile, therapy
compliance and influence of gas exchange and lung function pattern].
AB - A survey performed in 100 CPAP users indicated that irritation of the face, a
painful nose and nasal obstruction were among the most frequently mentioned
complaints in chronic CPAP users. In 132 normocapnic SAS patients a significant
improvement of PaO2 was shown, with a decrease of the alveolo-arterial oxygen
difference. This improved gas exchange was parallelled by a significant increase
in the FRC and TLC. Maybe a modulation in force of the respiratory muscles may be
involved. These data were more pronounced in obstructive sleep apnea than in
central sleep apnea. In 50 chronic CPAP users we could show a lower AHI
immediately after CPAP withdrawal after a previous prolonged treatment. These
findings may support the insufflation theory as a mechanism of action of CPAP.
Traditionally, mechanical splinting of the upper airway has been considered as
the dominant mechanism of action. Other mechanisms like changes in regulation of
breathing and decrease of the pharyngeal edema may be involved as well.
PMID- 9639950
TI - Tuberculous mediastinal lymphadenopathy.
AB - We report about 2 cases of isolated mediastinal tuberculous lymphadenitis
presenting without parenchymal infiltrates. Although rare, this mode of
presentation reminds the clinician that tuberculosis has to be included in the
differential diagnosis of mediastinal masses even in the absence of parenchymal
lesion. Both cases illustrate the value of mediastinoscopic examination to assess
the diagnosis.
PMID- 9639951
TI - Experimental induction of renal lesions in chickens.
AB - The present work was conducted to investigate the possibility of inducing renal
lesions in chickens subcutaneously or orally inoculated with E. coli [E. coli
O1K67(B12)], Staphylococcus aureus and Actinomyces pyogenes. The strains were
previously isolated from the kidneys of broilers showing different pathological
lesions. The gross lesions observed in the kidneys included enlargement,
congestion, haemorrhagic spots in addition to dilatation and distension of the
ureters. The microscopic lesions were mainly interstitial nephritis. The lesions
were acute and changed gradually to subacute or chronic nephritis. The glomerular
lesions were not common. The wall of the primary branches of the ureter and the
ureters was heavily infiltrated with inflammatory cells, also granular and
albuminous casts were seen in the renal tubules. The lesions were not related to
the inoculated pathogen, although they were more severe in chickens inoculated
with E. coli and Staph. aureus more than in Actinomyces pyogenes. Reisolation of
the inoculated pathogens was more successful from the birds inoculated
subcutaneously than from those infected orally.
PMID- 9639952
TI - [Occurrence of bacterial infectious agents in pathologically/anatomically altered
lungs of pigs and compilation of resistance spectra].
AB - The goal of this work was to investigate the type and etiology of bacterial
porcine pneumonia by analyses of autopsy findings made in the Tierarztlichen
Ambulanz Schwarzenbek, Aussenstelle der Freien Universitat Berlin, and in the
Institut fur Tiergesundheit, Milchhygiene und Lebensmittelqualitat der
Landwirtschaftskammer Westfalen-Lippe in Munster in the years from 1991 to 1993.
The evaluation of the results of the total 6560 autopsies (N = 6560) of pigs
shows: 1. Pneumonia as the main diagnosis was found in 24.4% (n = 1599), as the
second diagnosis in 14.3% (n = 941) of the sections. 2. Fattening pigs show signs
of pneumonia (43.2% (n = 1096) vs. 27.8% (n = 706); N = 2540) more frequently
than younger pigs. 3. The most frequently isolated etiologic agents from lung
specimens (N = 2337) were Pasteurella multocida (49.3%; n = 1152), Actinobacillus
pleuropneumoniae (5.4%; n = 125) and Bordetella bronchiseptica (5.3%; n = 124).
4. With increasing age of the isolation rate of Pasteurella multocida (piglets [N
= 210]: 21.4%, n = 45; fattening pigs [N = 652]: 61.8%, n = 403) and
Actinobacillus pleuropneumoniae (piglets: 1.4%, n = 3; fattening pigs: 7.1%, n =
46) increased while Bordetella bronchiseptica (piglets: 10.0%, n = 21; fattening
pigs: 1.1%, n = 7) and Haemophilus parasuis (piglets: 3.8%, n = 8; fattening
pigs: 0%, n = 0) were isolated at decreasing rates. 5. Most cultures of the lung
samples (N = 2337) showed multiple infections (1087 = 54.2%). 6. The highest rate
of single bacterial isolates was found for Pasteurella multocida (40.9%, n = 471,
N = 1152) in relation to Haemophilus parasuis (30.9%, n = 11, N = 36),
Actinobacillus pleuropneumoniae (24.0%, n = 30, N = 125), and Bordetella
bronchiseptica (20.2%, n = 25, N = 124). 7. Less than 10% of the examined
Pasteurella multocida, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica
and Haemophilus parasuis strains were resistant to tetracycline, oxytetracycline,
enrofloxacin and kanamycin, but more than 55% were resistant to sulfonamides.
PMID- 9639953
TI - [The problem of Q fever in zoo ungulates].
AB - Antibodies to Coxiella burnetii were recorded from approximately 13% of 469
ungulates which had been examined by means of micro-CFT (complement fixation
test). Particular reference is made to a Q-fever situation in a musk ox herd. The
results obtained from these investigations are likely to support the conclusion
that latent Q-fever infection may be expected to occur in ungulates and to grow
manifest in stress situations.
PMID- 9639954
TI - [Evaluation of an intracutaneous test using a Sarcoptes mite extract solution
(Acari: Sarcoptidae) as a method for detection of Sarcoptes mite-infested dogs].
AB - Sarcoptes infestation in dogs, caused by Sarcoptes canis, is a relatively common
disease in small animal practice. The parasites may induce severe allergic skin
reactions. By means of clinical symptoms a presumptive diagnosis should be made.
For ensurement detection of mites in skin scrapings is necessary, but it is not
easy to find the parasites. Serodiagnostic methods are helpful to confirm the
diagnosis. They indicate specific antibody (circulating IgE) titer.
Intracutaneous test by using allergen extracts as possible third way of
diagnostic methods was tested comparatively with the existing causaldiagnostic
procedures in 45 dogs with suspected scabies. Preconditions of own examinations
was mite antigen preparation. A mite extract solution of Sarcoptes suis was
prepared and 0.1 ml were applicated intracutaneously. In 14 dogs (31.11%)
allergic skin changes (Immediate reaction type 1) became apparent. The results
were opposed to both other detection methods--skin scraping (4 positive
findings/8.89%) and serodiagnosis (13 positive findings/30.77%).
PMID- 9639955
TI - [Polymerase chain reaction (PCR) for detection of BLV provirus-- a practical
complement for BLV diagnosis?].
AB - A typical infection with bovine leukemia virus (BLV) induces a permanent antibody
(Ab) response with high titers against BLV-antigens. In the last few years
atypical courses of infection with low or transient BLV-Ab-titers or even lack of
any detectable BLV-Ab-titers in animals with BLV-provirus integration have been
described. This makes it difficult to eliminate BLV infection from herds using
serological assays only. Whether or not polymerase chain reaction (PCR) is a
useful tool to complement serological Ab-assays in BLV-eradication in herds was
clarified in three ways: (i) different DNA-quick-preparations of blood were
examined in nested PCR, (ii) cows of a BLV infected herd that was involved in a
national eradication program were investigated for 6 months und (iii) BLV
provirus-variants occurring in this herd were differentiated. The results show,
that even by using PCR it was not possible to detect all infected animals all the
time and that eradication of BLV from this herd was not completed in this short
time. The PCR is useful for the investigation of herds and more sensitive than
ELISA. PCR using LTR-primers (34 positive cattle) was more sensitive than PCR
with env-primers (30 positive cattle). Using PCR 34 BLV infected cattle were
detected of which only 21 reacted in ELISA. Restriction enzyme analysis or
sequence analysis of PCR-amplificates allowed the detection of virus variants and
conclusions about the way of infection. PCR should be used for BLV-eradication in
cattle herds with low BLV-incidence, for the investigation of new outbreaks or
tumor cases in long term BLV free herds and for investigation of breeding cattle.
PMID- 9639956
TI - [Detection of Chlamydia psittaci infections in amphibians using an
immunofluorescence test].
AB - In amphibians, Chlamydia psittaci infections are known since 1982 as a fatal
disease. Only documented in two amphibian species, the pathogen seems to be
widespread in these coldblooded vertebrates. The detection of intracytoplasmatic
inclusion bodies and following examinations (electronmicroscopy) were necessary
for the postmortal diagnosis. In 26 amphibians (3 species) a specific
immunological testkit (immunofluerescence test) have been used. In 18 cases a
positive result was found. This is the first report about using an IFT for the
detection of Chlamydia psittaci in amphibians. Two new host species for this
pathogen were found, one bufonid anuran (Bufo maculatum) and the new Pachytriton
sp.
PMID- 9639957
TI - Pleural fluid: accuracy of computed tomography in differentiating exudates from
transudates.
AB - PURPOSE: To determine the accuracy of computed tomography in differentiating
pleural exudates from transudates when reviewed subjectively by two experienced
radiologists in a community hospital. METHODS: Computed tomography scans of 55
consecutive patients who had a thoracenteses within 10 days of the study were
retrospectively reviewed independently by two experienced staff radiologists.
They were asked to evaluate subjectively parietal pleural thickness (anterior,
lateral, posterior), attenuation of extra-pleural fat, and categorize pleural
fluid as loculated or free flowing. Radiographic findings were correlated with
biochemical results of thoracentesis (Light's criteria) to assess the accuracy of
computed tomography in differentiating pleural exudates from transudates.
RESULTS: For the diagnosis of an exudate, pleural thickening alone had the best
sensitivity and specificity (50%, 100%, respectively) with an accuracy of 55%.
CONCLUSION: Subjective evaluations for increased pleural thickness have a high
accuracy for diagnosing pleural exudates.
PMID- 9639958
TI - Atorvastatin (Lipitor).
PMID- 9639959
TI - As life ebbs, so does time to elect comforts of hospice.
PMID- 9639960
TI - Physician liability for suicide of noncustodial patient.
PMID- 9639961
TI - Regarding: "Trends in the incidence of upper extremity soft tissue malignancies:
a 40-year review of the Connecticut State Tumor Registry".
PMID- 9639962
TI - Burdensome Medicare guidelines.
PMID- 9639963
TI - Leg edema secondary to bladder distention.
PMID- 9639964
TI - How to evaluate national suicide programs?
PMID- 9639965
TI - Hotlines and mental health services.
PMID- 9639966
TI - Arranging the death of a king.
PMID- 9639967
TI - The posttotalitarian pattern of suicidal behavior: impact on youth.
PMID- 9639968
TI - Letter across the Pacific.
PMID- 9639969
TI - A clinical-psychological approach to suicidal behavior in depression from Moscow.
AB - This contribution strives to familiarize Western readers with the theoretical
concept of suicidal behavior which was developed at the Department of Suicidology
of Moscow Psychiatric Research Institute and has been in use there for the last
two decades. In describing this approach the paper concentrates on what
differentiates it from traditional Western management without making value
judgments about either approach. Such an account of the concept and its
development will hopefully afford the reader an opportunity to arrive at his or
her own conclusions regarding its clinical value.
PMID- 9639970
TI - Empowered consumers and telephone hotlines.
AB - Today health-care budgets are rapidly being cut and services streamlined.
Volunteers and nonprofit agencies have been commissioned to take on part of the
burden. Currently they are expanding and reorganizing their services to meet the
new demand. Telephone crisis lines, in particular, have the potential to take on
a large share of consumer needs--they are always available and turn no one away.
Unfortunately, crisis lines have their own set of problems. Although the bulk of
work is performed by volunteers and represents a minimum of expense, the
clientele is varied, the workload unpredictable. Staff at the line need to
balance the needs of their regular callers with crisis calls and their volunteer
needs by establishing comprehensive policies. This article looks at just a few of
the challenges these lines face, and attempts to analyze the options, keeping the
rights of modern consumers in mind.
PMID- 9639971
TI - Suicides in Hong Kong and Australia.
AB - Although the suicide rate for both Hong Kong and Australia was about 12 per
100,000 in 1994, the age- and gender-specific rates, methods of suicide, and time
trends vary greatly for these two places. This paper explores the possible
social, economic, and cultural background to explain this discrepancy. We used
the official suicide death statistics of Hong Kong and Australia for the period
1984-1994. We calculated age-standardized suicide rates in order to take into
account the differences in the age composition between the two countries and
years. We employed a log-linear (Poisson) model to detect the age- and gender
specific trends, and to determine whether there were specific age or gender
groups whose suicide behavior had changed significantly between 1984 and 1994.
Hong Kong experienced a slight increase in suicide rate for both genders in the
years 1984-1994, whereas Australia experienced a cubic trend for both genders
during the same period and a rise in suicide rate in recent years. The suicide
rate in Hong Kong increased with age, with a sharp increase (nearly four times
the average) among the group aged 75 or over. A relatively low gender ratio
(male:female) was also observed in Hong Kong, whereas in Australia there was not
much difference in suicide rates among all age groups, though the suicide rate of
the group aged 75 or over was 1.2 times the average. The gender ratio in
Australia was higher, and the male suicide rate was four times higher than that
of females. The Hong Kong suicide rate in females was twice that of Australia,
whereas the Hong Kong male suicide rate was about half that of Australia. Jumping
and hanging were the most common methods of suicide in Hong Kong, accounting for
more than 80% of all suicide deaths. Poisoning (including gas poisoning) was the
most common method used in Australia, with firearms being more common among young
males. Australia had a higher years of potential life lost (YPLL) than Hong Kong
because of the higher suicide rate among young males (aged 15-24). The high
suicide rate among the elderly in Hong Kong raises the possibility that medical
and social support to the elderly could be enhanced. The high female suicide rate
in Hong Kong could be related to workload, responsibility, and expectations. The
high suicide rate in Australia among males aged 15-24 was disturbing.
Availability of the suicide methods is certainly one explanation for the
difference in suicide methods used in Hong Kong and Australia.
PMID- 9639972
TI - A study of elderly suicides in Hong Kong.
AB - Hong Kong has one of the highest rates of suicide among the elderly in the world.
Most of the existing suicide prevention programs have had very little effect on
the elderly, who rarely utilize these programs. This study aims to help in
understanding the problem, so that effective prevention can be provided to this
high-risk group of suicidal people. Specifically, the study (1) describes the
characteristics of the suicidal elderly, (2) investigates the reason(s) why the
elderly are in distress and become suicidal, and (3) formulates a policy and
service model to reach the elderly high-risk group. This research project
involves secondary data analysis. Police records on elderly suicide cases in 1992
were scrutinized to find out the major reason(s) for fatal death in the elderly.
Our study points out those districts that are more crowded and have fewer medical
and social facilities tended to have higher suicide rates. Most of the deaths
occurred at home or nearby, and the suicidal elderly were alone before their
death. The majority of elderly suicide victims suffered from chronic diseases.
Very few of them, however, were totally dependent: About 40% of the cases had
consulted medical practitioners, and 27% had consulted psychiatrists within one
month before their deaths. Close to 70% of the cases had indicated to family
members or other their suicidal thoughts, and many of them had revealed numerous
suicidal indications. Both policy and practice issues are discussed in light of
the findings.
PMID- 9639973
TI - Attempted suicides in Ankara in 1995.
PMID- 9639974
TI - [Evaluation of bacteriological research data and laboratory symptoms of infection
in the diagnosis of congenital and acquired infections].
AB - The predisposition of the newborns to contract infections diseases is dependent
upon the limited efficiency of their immune mechanisms. Congenital infections
amount to 5.7% in the research material, and the acquired infections 1.15%. The
isolation of the microorganism is the basis for treating infections-the profiles
of the pathogenic bacterial in flora were subjected to analysis. Im generalised
infections Stafphylococcus epidermidis makes 56.6% and E. Coli accounts for 87.5
of the infections of the urinary system. In our research the late sepsis and
pneumonia are more frequently the result of the hospital infection (14.2%) in the
cases of congenital infections-pneumonia and the infection of the urinary system
(72%). Hematologic indicators such as: leucopenia, thormbocytopenia, I/T are
distinct infection markers (those were found in 31% of the cases). The CRP
protein shows the lowest values in congenital infections, still monitoring its
level is useful for assessing the effectiveness of the undertaken antybacterial
treatment. The newborns of male sex (58%) more often prone to infection.
Pneumonia is the manifestation pertaining to an organ in 70% of congenital
infections, the infection of urinary system amounts to 17.1%.
PMID- 9639975
TI - The concentration of cotinine in urine, colostrum and amniotic fluids within the
system mother-baby.
AB - The findings obtained by the authors of the thesis submit the new cognitive
values to the diagnosis of pathology of pregnancy i.e. the influence of nicotine
on the organisms of a mother and a new-born child, estimated by the assay of
cotinine, the most important metabolite of nicotine. The authors lay a particular
stress on the "colostrum-milk way" in the mother-child relationship and this is
that needs to be emphasized in this thesis.
PMID- 9639976
TI - The average quantitative concentration of cotinine within the system pregnant
woman-baby.
PMID- 9639977
TI - [Surgical treatment of uterine leiomyomas in infertile patients].
AB - Retrospective analysis of the results of operative treatment for uterine
leiomyomas was carried out. Our screening included the total of 186 patients. One
hundred and eight women responded to the questionnaire /58%/. Respondens were
treated for sterility in the period between 1990-1995. Successful operative
treatment, expressed as pregnancy rate reached 29.7%.
PMID- 9639978
TI - [Trinucleotide repeats polymorphism of the androgenic receptor gene in the
detection of carriers of androgen insensitivity syndrome].
AB - Androgen insensitivity syndrome (AIS) is caused by mutation in androgen receptor
(AR) gene. This phenomenon leads to the defect of the virilization of the
external genitalia and is one of the causes of human male pseudohermaphroditism.
Molecular diagnosis of AR gene mutations is very complex because of heterogeneity
of AR mutations. AIS is X-linked recessive trait and therefore the simple
diagnosis of AIS carriers is a very important problem. Detection of AIS carriers
by using the analysis of CAG repeating sequence polymorphism of exon 1 or AR gene
is reported.
PMID- 9639979
TI - [The significance of cardiography in the diagnosis of cardiac ectopia of the
fetus].
AB - Retrospective analysis of echocardiographic examinations of 7 fetuses with
ectopia cordis was presented. The majority of abnormalities were found in low
risk pregnancies. There was only one case of isolated ectopia cordis with normal
heart anatomy and no extracardiac malformations. There was no survival.
Theoretically the prenatal diagnosis of isolated ectopia cordis may help to
choose the proper term, place and method of delivery and also to plan the optimal
care of newborn. Parents should be counseled about the prognosis in such cases,
at the tertiary center, after detailed fetal echocardiography.
PMID- 9639980
TI - [The analysis of factors which affect qualification of pregnant women as cord
blood donors].
AB - Authors' analysis refers to reasons for which some women did not meet criteria
for the programme of collection of cord blood by The Cord Blood Bank in Warsaw.
The main reasons were: 1) reactivation of infection with CMV virus, 2)
complications of delivery and 3) technical problems. We present also preliminary
results of blood tests aimed at identification of some viral (hepatitis B and C,
HIV, CMV), bacterial (Treponema pallidum) and protozoal infections (Toxoplasma)
in the selected group of pregnant women.
PMID- 9639981
TI - [Ultrasound diagnosis of four fetuses with Fraser syndrome during pregnancy].
AB - The authors present results of sonography analysis of four fetuses with Fraser
syndrome. First woman had prenatal diagnosis by ultrasounds and ascites of fetus
with polyhydramnion were diagnosed in two of her successive pregnancies. The
second pregnant woman was observed by ultrasound and lack of kidney was detected.
The third pregnant one was diagnosed at first trimester of pregnancy and results
of sonography examination were at norm. After delivery, Fraser syndrome in all of
these children was diagnosed. Findings on sonography included: ascites of fetus,
polyhydramnion, hydrocephalus and nonvisualization of kidney. Sonography is more
efficient in the diagnosis of Fraser syndrome in a fetus whose parents had had a
previous affected child because of diverse anomalies were observed.
PMID- 9639982
TI - Emergency medicine in the problem-based learning curriculum.
PMID- 9639983
TI - Common sports injuries seen by the primary care physician. Part II: Lower
extremity.
AB - Sports medicine is the science of caring for the medical and surgical needs of
athletes and their injuries. Injuries of the upper extremity were dealt with in
Part I in a previous article. Part II deals with injuries of the lower extremity.
Trochanteric bursitis and hamstring strains are treated with rest,
rehabilitation, and correction of training errors. Patellofemoral pain syndromes
require accurate diagnosis and usually a rehabilitative program. Injuries to the
medial collateral ligament are very common, but can be associated with tears of
the meniscus and cruciate ligaments. The latter two often require surgical
intervention. Ankle sprains are graded by severity. The most severe can result in
chronic pain or instability, but most respond well to functional bracing and
progressive return to activity.
PMID- 9639984
TI - 10 common medicolegal questions on HIV infection.
AB - As the HIV pandemic continues, physicians will increasingly face both medical and
legal questions when caring for these patients. Using a question and answer
format, we provide in this paper, a guide to physicians in Hawaii on the
medicolegal issues surrounding HIV infection.
PMID- 9639985
TI - Fat chance of immunomodulation.
PMID- 9639986
TI - Tumour immunology: false hopes--new horizons?
PMID- 9639987
TI - Pediatric rheumatology: autoimmune mechanisms and therapeutic strategies.
PMID- 9639988
TI - Innate T-cell immunity to nonpeptidic antigens.
PMID- 9639989
TI - CD1-restricted T cells and resistance to polysaccharide-encapsulated bacteria.
PMID- 9639990
TI - Collagen receptor signalling in platelets: extending the role of the ITAM.
PMID- 9639991
TI - Enkelytin and opioid peptide association in invertebrates and vertebrates: immune
activation and pain.
PMID- 9639992
TI - Gap junctions: a novel route for direct cell-cell communication in the immune
system?
PMID- 9639993
TI - Preferential expression of TCR V alpha regions in CD4/CD8 subsets: class
discrimination or co-receptor recognition?
PMID- 9639994
TI - The role of endosomes and lysosomes in MHC class II functioning.
PMID- 9639995
TI - Immune modulation by zinc: clues from immunoglobulin structure and function.
PMID- 9639996
TI - Genetics of type I diabetes.
PMID- 9639997
TI - The role of dendritic cells in contact hypersensitivity.
PMID- 9639998
TI - An experimental study of the esthetic effect of facial profiles.
AB - In this study good-looking "male" and "female" as well as ugly facial profiles
were shaped by 104 lay persons using an especially constructed device according
to specific instructions. These profiles were photographed and subsequently
evaluated using a series of parameters from soft tissue profile analyses.
Although some significant mean value differences were found between the good
looking and ugly profile variants, they were not substantial. In contrast,
markedly significant differences were revealed between the variances of all
variables. In some instances the variance of the ugly profiles was more than 3 to
4 times higher than that of the good-looking profiles. These findings were
convincingly confirmed when statistical distribution of the data was established
and compared. This implies that perception of beauty is associated with
regularity of facial features and is conveyed by measurement values which are
located close to the mean. Ugliness is associated with extreme deviations from
the latter in either direction. Apart from the facial proportions, the degree of
convexity or concavity of facial profile and their sequence seem to be important
for the esthetic effects. "Male" profiles in contrast to "female" profiles
exhibited more conspicuous facial features such as pronounced convexity and
concavity.
PMID- 9639999
TI - Class II correction with magnets and superelastic coils followed by straight-wire
mechanotherapy. Occlusal changes during and after dental therapy.
AB - The investigation comprised 18 consecutively selected patients, mean age 14.7
years at the start of treatment, with Class II malocclusion, deep overbite and
space deficiency in the maxillary arch. The first phase of the treatment
consisted of 6 months simultaneous distal movement of maxillary first and second
molars with repelling samarium-cobalt magnets on one side and a superelastic
nickel-titanium coil on the contralateral side together with an anterior
biteplane to achieve bite opening. For the second phase of the treatment, a
straight-wire appliance was used for an average treatment time of 1.3 years.
Lateral head radiographs and dental casts were available at the start of
treatment, after molar distalisation, at the end of treatment and 1 year post
treatment. The treatment resulted mainly in dental changes. The dental Class II
molar relation was corrected to Class I by bodily distal movement of maxillary
molars and by mesial movement of the mandibular molars. The correction of molar
relation was significantly greater on coil sides than on magnet sides, mean 3.4
mm, and 3.0 mm, respectively. Despite anchorage loss associated with the
maxillary molar movement, i.e. mesial movement of the maxillary incisors (mean
1.8 mm), the net overjet was reduced, mean 2.5 mm, by the use of Class II
elastics. The average net improvement of bite opening was 2.6 mm, mainly due to
extrusion of mandibular and maxillary molars. During the 1-year post-treatment
period no significant dental or skeletal changes were found. The long-term
implications of the treatment results need further consideration.
PMID- 9640000
TI - Frictional forces when rectangular guiding arches with varying edge bevel are
employed.
AB - In orthodontic treatment employing arch guided tooth movement, rectangular wires
are usually used to achieve three-dimensional controlled tooth movement. In the
intention to optimize sliding mechanics and to improve the comfort of patients,
edge beveled rectangular orthodontic wires are offered by different
manufacturers. The objective of the study presented was to investigate the
influence of differing but defined wire roundings on sliding mechanics of canine
retraction. Employing the 0.018" slot system, 0.016" x 0.022" standard steel
wires (Remaloy and Remanium, Dentaurum Comp.) were tested. Force loss due to
friction during canine retraction was determined using the Orthodontic
Measurement and Simulation System (OMSS). In the arch guided distalization of
canines, the average loss of force caused by friction was determined to be
approximately 50%. Comparing wires with different edge bevel, the rounded wire in
contrast to the wire with sharpest edge configuration results in a reduction of
friction. Even a moderate wire rounding of the 0.016" x 0.022" steel wire results
in about 10% reduction in frictional losses. However, dynamic analysis of tooth
movement with the OMSS shows that there is no further improvement of sliding
mechanics using wires with edge bevel exceeding the standard rounding of
rectangular wires. In contrast, a strong edge bevel may result in a considerable
loss of leveling.
PMID- 9640001
TI - Condylar restoration after early TMJ fractures and functional appliance therapy.
Part I: Remodelling.
AB - The aim of this study was to measure quantitatively and to analyze the process of
condylar restoration during and after functional appliance therapy with an
activator in children and juveniles who had sustained condylar fractures. Spiral
computed measurement of condylar morphology was performed in order to quantify
the association described in the literature between condylar remodelling and age
as well as certain types of fracture. Nineteen patients with an average age of
13.4 years, who had sustained a functionally treated unilateral condylar fracture
4.9 years earlier on average, were included in the present study as the follow-up
group. Twenty patients, who had sustained a unilateral fracture at an average age
of 8.1 years and had been treated functionally for 6 to 8 months, formed the
treatment group. The condylar dimension and the condylar neck length of the
ipsilateral and of the contralateral temporomandibular joints were measured from
the axial and parasagittal reconstructions and were compared on the basis of sex,
age and fracture type. The mediolateral condylar dimension of the follow-up group
showed a sex-specific difference of 0.2 cm on the contralateral side and 0.4 cm
on the ipsilateral side. The fracture side condyle indicated a relative
mediolateral decrease of 4.2% and an anteroposterior increase of 12.6%.
Shortening of the condylar neck and excessive bony overgrowth were found to occur
more often in fractures with displacement and in low fracture types. The "10
plus" subgroup at time of trauma showed a significantly greater variation and
greater differences in mediolateral and anteroposterior condylar dimension than
the younger patients.
PMID- 9640002
TI - Evaluation of the profile line in prognathic patients in the Saxony-Anhalt region
of Germany.
AB - The aim of the present study was to investigate the soft-tissue morphology and
profile line of prognathic patients in the Saxony-Anhalt region of central
Germany. To this effect, the profile photographs and lateral cephalograms taken
at treatment start for 34 adults (17 female patients, mean age: 22.6 years; 17
male patients; mean age: 23.2 years), Class III subjects who had not undergone
orthodontic treatment, were measured and, by means of statistical analysis, the
findings were compared with those of an age-matched control group (17 female
subjects, mean age: 21.4 years; 17 male subjects, mean age: 23.8 years). Patients
with Class III anomalies had a significantly longer and thinner lower lip and a
smaller lower subnasal angle than the control subjects. The lower face was
markedly enlarged. Furthermore, the osseous profile line was significantly
flatter and the soft-tissue convexity was considerably reduced compared with the
control group. Hence the prognathic patients of central Germany manifested
typical features of the prognathic profile line. To elucidate typical regional
features, further comparative studies are required.
PMID- 9640003
TI - Incisor torque by means of a modified Teuscher activator. Three case reports.
AB - It is generally accepted that in the treatment of Class II, 1 malocclusion
classical activators may tip the upper incisors considerably. In comparison, in
the cases described, an even better torque control was obtained. It has been our
clinical experience that with the modified Teuscher activator it is possible to
control upper incisor inclination and in some cases it is even possible to induce
active palatal root torque. The appliance is relatively comfortable with good
vertical retention even without headgear.
PMID- 9640004
TI - Oculo-facio-cardio-dental (OFCD) syndrome.
AB - The association of facial dysmorphy, congenital cataracts, microphthalmia, heart
disease, and dental radiculomegaly is very rare. We describe a girl with atrial
septal defect, unilateral congenital cataract, unilateral microphthalmia,
radiculomegaly of incisor and canine teeth with open apices and other dental
crown anomalies. This combination of symptoms clearly represents a distinct
syndrome and has recently been described as oculo-facio-cardio-dental (OFCD)
syndrome.
PMID- 9640005
TI - Orthodontic treatment of a Class II, 1 malocclusion including extractions of the
4 first molars. Case report.
AB - Orthodontic treatment of a Class II, 1 malocclusion in a 13-year-old boy is
demonstrated. The first molars were extracted and an edgewise appliance was used.
PMID- 9640006
TI - Sexually transmitted diseases and adolescents.
PMID- 9640007
TI - Quality parental decision making and distress.
AB - The purpose of this study was to test three hypotheses in the context of
parenting an adolescent: (1) socioeconomic status (SES), parental gender, marital
status, and age of parent will be predictors of quality decision-making for
parents of adolescents; (2) as predispositional and situational distress
increase, quality decision making among these parents will decrease; and (3)
predispositional distress will be as strong a predictor for quality decision
making as situational distress. The sample included 123 parents of adolescents
ages 13 to 19 years. SES was the only significant predictor (11%) for parental
decision making; the higher the SES, the more quality in decision making
reported. Moderate negative correlations were obtained between predispositional
distress and quality decision making and situational distress and quality
decision making. Both predispositional distress and situational distress
contributed equally as predictors of quality decision making.
PMID- 9640008
TI - The Hispanic teen mother's origin of birth, use of prenatal care, and maternal
and neonatal complications.
AB - The purpose of this study was to describe and compare differences in
demographics, prenatal care use, and pregnancy, labor, postpartum, and neonatal
complications for 129 pregnant Mexican-American adolescents who were either born
in the United States or born in Mexico. A significant finding was that 25% of the
teens, regardless of origin of birth, received either inadequate or no prenatal
care. The findings of this study will be useful to clinicians providing health
care for Hispanic teens and for administrators and policy makers who affect the
types of health care and education available to these young mothers.
PMID- 9640009
TI - Reducing teenage and unintended pregnancies through client-centered and family
focused school-based family planning programs.
AB - Achievement of the national health goal to reduce teenage and unintended
pregnancies through family planning requires a holistic approach to primary
prevention. Building upon Rogers' Science of Unitary Human Being, Orem's Self
Care Theory, and Rosenstack's Health Belief Model, a client-centered and family
focused school-based family planning program is proposed as a means to achieve
the health goal. FNPs play a pivotal role in development and successful
implementation of such a program.
PMID- 9640010
TI - The interpretation of infant pain: physiological and behavioral indicators used
by NICU nurses.
AB - The purpose of this descriptive study was to identify the indicators used by
neonatal nurses to interpret the experience of pain in infants in a Neonatal
Intensive Care Unit (NICU). A sample of 72 NICU nurses completed a structured
questionnaire to identify the physiological and behavioral indicators they used
to interpret the experience of pain in the infants entrusted to their care. The
10 pain indicators used by more than 50% of the nurses, listed in decreasing
order of frequency, were: fussiness, restlessness, grimacing, crying, increasing
heart rate, increasing respirations, wiggling, rapid state changes, wrinkling of
forehead, and clenching of fist. These findings are consistent with existing
literature, are compatible with the stress cues identified in Als' Synactive
Theory of Development, and lend support to the use of such measures for the
assessment of infant pain.
PMID- 9640011
TI - Discharging ventilator-dependent children: a continuing challenge.
AB - Preparation of ventilator-dependent children, their families, the health care
system, and communities for community-based care has presented many challenges
over the past two decades. This article reviews some of the challenges that have
been resolved by interdisciplinary discharge planning, discharge protocols, case
management approaches, and collaborative care. Unresolved challenges continue to
prevent children with special health care needs (CSHCN) from being served
adequately by the health care system, the legal system and the community in this
era of cost containment. Current literature, existing research and clinical
observation were used to develop nursing implications and recommendations for
continued research.
PMID- 9640012
TI - Community child health nursing: a New Zealand experience.
PMID- 9640013
TI - The nurse's role in the prevention of child abuse and neglect: Part II.
PMID- 9640014
TI - I.V. HOUSE: pediatric nurses contribute to refinement of i.v. protector.
PMID- 9640015
TI - [Evaluation of visual evoked potentials in partial optic nerve atrophy].
AB - PURPOSE: Parameters of visual evoked potentials in partial optic nerve atrophy in
different aetiology were studied. MATERIALS AND METHODS: The study involved 48
patients (68 eyes) with partial optic nerve atrophy from neuritis, toxic,
arteriosclerosis and trauma. The tests of visual evoked potentials were performed
by the use of UTAS E-1000 computer system in all patients with the use of pattern
and flash stimulation. RESULTS: Amplitude of all waves were reduced in 74%
patients using "pattern" and in 61% patients using "flash" stimulation. Latency
of wave P2 was delayed in all patients with optic nerve atrophy from
arteriosclerosis. Latency of P100 wave and N1 wave were not delayed in patients
with optic nerve atrophy from toxic neuropathy. CONCLUSIONS: Estimation of
latency of the VEP may be useful in diagnosis of the partial optic nerve atrophy.
Variety of records of VEP indicate different degree of disturbances of nerve
conduction.
PMID- 9640016
TI - [The condition of the posterior capsule in pseudophakic retinal detachment].
AB - PURPOSE: Analysis of condition of posterior capsule in pseudophakic retinal
detachment. MATERIAL AND METHODS: 37 pseudophakic eyes of 35 patients with
retinal detachment were examined. The condition of posterior capsule and the time
when retinal detachment was observed were analysed. CONCLUSION: Disruption of the
posterior capsule as a complication of cataract surgery was associated with a
significant elevated risk of retinal detachment. Uncomplicated posterior capsule
prevented acid from vitreous delayed retinal detachment, but is not eliminated,
especially in risk factor cases.
PMID- 9640017
TI - [Late effects after anterior intraocular lens implantation].
AB - MATERIAL AND METHODS: During ten years, 890 operations of cataract with anterior
chamber intraocular lens implantation were performed. TWO GROUPS OF EYES WERE
OBSERVED: Eyes after planned intracapsular cataract surgery and eyes in which
intraoperative complications occurred making impossible to apply posterior IOL.
PURPOSE: To evaluate late complications and functional status of the eye.
RESULTS: Our results indicate that anterior chamber intraocular lens implantation
yields in many cases good visual acuity and, although not free of complications,
is a safe procedure.
PMID- 9640018
TI - [Corneal astigmatism after trabeculectomy].
AB - PURPOSE: The aim of the present study was to investigate the effect of
conventional and mitomycin trabeculectomy on the corneal astigmatism. SUBJECT AND
METHODS: Measurements with the use of computer-assisted videokeratography (Eye
Sys) were performed in 34 glaucoma patients who underwent trabeculectomy. Color
coded topography maps were analyzed to obtain astigmatic data. RESULTS: The mean
surgically-induced astigmatism in conventional trabeculectomy group was 2.2 D and
in the mitomycin group 4.0 D, 1 day post-op, 1.3 D and 3.0 D after 10 days and
0.4 D and 1.1 D after 3 months, respectively. CONCLUSION: There was an apparent
correlation between the amount of induced astigmatism and the use of mitomycin.
This may be related to the impaired healing process of trabeculectomy wound and
lower intraocular pressure in the mitomycin group.
PMID- 9640019
TI - [Evaluation of the rate of ophthalmologic complications of insulin-dependent
diabetes mellitus in children and adolescents].
AB - PURPOSE: To detect very early changes of the visual organ among 156 young
patients with diabetes mellitus. MATERIAL AND METHODS: Beyond the traditional
ophthalmological examination, the fluorescein angiography and electroretinography
were performed. RESULTS: On the whole, the changes were confirmed in 56 children
(35.8%). Diabetic retinopathy was observed in 24 cases (15.4%), changes of the
lens revealed in 52 children (33.3%). Among 40 children examined with electro
retinography 25 had decreased amplitude and prolonged latency of oscillatory
potentials. CONCLUSIONS: Fluorescein angiography is the more sensitive method of
examination than routine ophthalmoscopy. Electro-retinography seems to be
important in the diagnosis of early changes of diabetic retinopathy.
PMID- 9640020
TI - [Changes in the corneal curvature in soft contact lens users].
AB - PURPOSE: This study was designed to show the corneal topography changes induced
by contact lens use. MATERIAL AND METHOD: The corneal topography has been
examined in 19 contact lens users (37 eyes). RESULTS: The mayor changes in
topography have been found between 6th and 18th week after stopping the contact
lens wearing.
PMID- 9640021
TI - [Examination of ocular lesions in drug abusers in Poland].
AB - The authors present ocular symptoms in 116 drug abusers. They have observed optic
atrophy and defects in visual field in 9 cases, reduced convergence in 8 cases,
slow pupillary reaction in 9 cases, ptosis in 3 cases, nystagmus in 2 cases,
retinal haemorrhages in the nerve fibre layer in 2 cases, myopia in 45 cases and
blepharoconjunctivitis in most of cases. The authors want to indicate the
principal ocular signs in drug abusers in our country.
PMID- 9640022
TI - [Bilateral isolated posterior scleritis].
AB - A case of 44-year-old man is presented with no simultaneous bilateral posterior
scleritis with amelanotic chorioidal mass initially diagnosed as intraocular
tumor. The patient showed the features of nodular posterior scleritis without
associated systemic disease. The case presented symptoms of severe eye pain,
unilateral proptosis, hyperemia and dilatation of scleral, episcleral and
conjunctival vessels. Diagnosis was made on the basis of B-scan ultrasonography.
Differential diagnosis excluded melanoma malignum chorioideae, orbital
cellulitis, Graves ophthalmopathy, orbital cellulitis, cavernous sinus thrombosis
and carotid-cavernous fistula. The patient did not respond well to systemic
steroids given in high doses and during slow tapering at the dosage of 30 mg
prednisone once per day the symptom of uveal effusion syndrome occurred. After 10
months of steroid therapy the signs of disease like mild hyperemia and tenderness
were still present. The adjunction of cyclosporin improved the disease and caused
the remission.
PMID- 9640023
TI - [Ocular manifestations of the HELLP syndrome].
AB - A 23-year old female patient diagnosed as HELLP syndrome (H-hemolysis, EL
elevated liver enzymes, LP-low platelets) was admitted during her 34th week of
first pregnancy. After caesarean section she received hypotensive and
anticoagulant treatment and blood transfusion. Her general condition was
improved. The ocular manifestations (i.e. blurred vision, retinal oedema nad
hemorrhages) were seen on the 10th postpartum day in both eyes. The ocular
changes disappeared 4 month later.
PMID- 9640024
TI - [Pleoptic therapy in anisometropic and strabismic amblyopia].
AB - The study aims at describing the current trends in pleoptic treatment with a
special attention paid to the practised exercises. On the basis of literature a
short review of the pathogenesis of amblyopia with or without strabismus is
presented. The need for careful choice of the treatment according to specific
conditions in each subject is emphasised. The importance of active pleoptic
therapy in cases with or without strabismus is particularly pointed out. In
anisometropia contrast sensitivity is decreased, differentiation of optotypes put
in line and shape differentiation are worsened, ability to discern figures and to
accommodation are impaired. Amblyopia with strabismus leads to decrease in space
orientation ability, impairment in following movement, prolongation of saccadic
movement and of eye-hand coordination time. The types of visual dysfunction
mentioned above determine the exercises which should be recommended in a given
case. Examples of exercises are presented and the range of improvement possible
to achieve is documented.
PMID- 9640025
TI - Treatment of the wounded at Chipyong-ni.
PMID- 9640026
TI - Utilization of combat stress control detachments.
PMID- 9640027
TI - Subject: military disaster medicine.
PMID- 9640028
TI - Mental health nursing support during Operation Sea Signal: Cuban/Haitian
humanitarian mission.
AB - Joint military humanitarian missions provide challenges and rewards for mental
health nursing not found in the garrison mission. A primary challenge is to
develop and implement programs that benefit the various populations inherent in
such missions. During Operation Sea Signal, several programs, such as migrant
adult day treatment, halfway house, outreach, and inpatient, led to the overall
enhancement of mental health nursing care for the Cuban and Haitian migrants. It
also gave the participating mental health nursing team of professionals and
enlisted technicians the opportunity to develop their nursing expertise and
sensitivity in a culturally diverse situation.
PMID- 9640029
TI - Operational stress control in the former Yugoslavia: a joint endeavor.
AB - The military has developed specialized mental health teams to evaluate and treat
soldiers diagnosed with stress reactions and neuropsychiatric disorders. The
response of these mental health teams in support of the year-long peace
enforcement mission to Bosnia-Herzegovina is reviewed. Demographics and
operational stressors are examined. Stress control doctrine is tested and
revised. Credibility with leaders, chaplains, and medical personnel is achieved
through rapid response to serious injury or fatality. Emphasis is placed on
successful marketing strategies, stress management and suicide prevention
classes, prompt access to care, and decreasing the stigma of mental health
through education. Coordination of mental health assets promotes synergy and
mission accomplishment.
PMID- 9640030
TI - Psychological health and trauma in male and female soldiers.
AB - This study assessed the effect of premilitary and military trauma on the
psychological health of more than 1,000 female and male active duty soldiers.
Questionnaire data provided information on demographics, history of trauma
exposure, and general psychological health as assessed by the Brief Symptom
Inventory (BSI). The results indicated that females reported experiencing more
sexual traumas and males reported more nonsexual traumas. BSI subscale scores
indicated poorer psychological health among all of the subjects compared with BSI
normative groups and other Army soldiers. The need for military norms for the BSI
is discussed.
PMID- 9640031
TI - Early syphilis in an active duty military population and the surrounding civilian
community, 1985-1993.
AB - Syphilis among active duty soldiers at Fort Bragg, North Carolina, and the
nonmilitary population of Cumberland County was examined during a 9-year period
encompassing the most recent nationwide syphilis epidemic. A total of 762 cases
of primary and secondary syphilis were recorded between 1985 and 1993, 27% of
which occurred in soldiers. The epidemic struck both military and civilian
populations simultaneously; epidemic curves in the two populations were parallel,
peaking in 1990-1991, with highest annual incidences of 122.6/ 100,000 (military)
and 48.0/100,000 (civilian). Individual risk factor data were not available for
analysis, but a relationship was observed between primary and secondary syphilis
diagnoses in both populations and cocaine arrests in Cumberland County. Our
findings provide epidemiological support for a high degree of interplay between
the military and the surrounding civilian communities that has significant
implications for control of sexually transmitted diseases. Enhanced collaboration
between military and civilian public health authorities is essential to the
control of syphilis and other sexually transmitted diseases.
PMID- 9640032
TI - Senior executive behaviors for the Army Dental Care System of the 21st century.
AB - Challenges will most likely confront the Army Dental Care System as it moves into
the next century. Like any other learning organization, the Army dental care
system must develop a continuous stream of dynamic leaders to direct its
evolution if it wants to survive. Using the Delphi method, the investigators
surveyed senior dental leaders to determine the attitudes and behaviors believed
to be required to perform successfully as commanders, residency directors, and
senior staff officers. The essential executive behaviors appear to be consistent:
be honest, act with integrity, be accountable for your actions, be dedicated to
mission accomplishment, and perform your duty with care and compassion. Relying
solely on ratings assigned to the behaviors, discriminant function analyses could
predict proper group membership with an accuracy of 79.4%. When demographic
information was included, prediction accuracy improved to 96.7%.
PMID- 9640033
TI - Temporary dental restorative materials for military field use.
AB - New temporary dental restorative materials are an important military requirement.
This study compares the critical properties of the currently used temporary
material, reinforced zinc oxide-eugenol (ZOE), with those of a glass ionomer
restorative material (GI), a high-viscosity modified glass ionomer material
(MGI), and two resin-modified glass ionomer materials (RMGIs). Properties tested
included compressive and tensile strength, rigidity, hardness, bond strength,
working and setting times, and storage stability. Ranked results for compressive
strength, rigidity, and hardness were MGI > GI > RMGI > ZOE; for tensile strength
they were RMGI > MGI > GI > ZOE; and for storage stability they were ZOE > MGI >
GI > RMGI. Working and setting times were all within reasonable clinical limits,
and bond strength was heavily dependent on tooth surface preparation. Although
none of the materials tested met all of the ideal requirements, the high
viscosity glass ionomer material offers the most promise for military field use.
PMID- 9640034
TI - Dental sealants: prevalence and need in U.S. military recruits.
AB - This paper explores the need for and the prevalence of dental sealants in U.S.
military recruits. The data come from the 1994 Tri-Service Comprehensive Oral
Health Survey. Data were collected on 2,711 Army, Air Force, Marine Corps, and
Navy recruits at one recruit in-processing center per service. Women and
minorities were oversampled. Both bivariate and logistic regression analysis were
done on the need for at least one dental sealant and the prevalence of at least
one dental sealant in recruits. Weighted data (101,072) were used for the
bivariate analyses; unweighted data were used in the regressions. Results show
that 8.7% of recruits need dental sealants and that 14.8% have dental sealants.
Need for dental sealants varies across branch of service only, whereas prevalence
of dental sealants varies across age, race, and branch of service. The cost
effectiveness of dental sealants in this population should be established.
PMID- 9640035
TI - Ventilator-related Acinetobacter outbreak in an intensive care unit.
AB - An outbreak of 16 cases of ciprofloxacin-resistant Acinetobacter baumannii
(calcoaceticus subspecies anitratus) infections occurred during a 7-month period
in a medical intensive care unit. Fifteen of the patients developed pneumonia
associated with ventilator support. Possible sources considered in the outbreak
investigation were sinks, ice, personnel, patients on multiple antibiotic
therapy, reusable ventilator circuits, and hemodialysis. The equipment and
environment associated with the outbreak were cultured. Patients on ventilators
were significantly more susceptible to Acinetobacter nosocomial infection
compared with the rest of the patients in the medical intensive care unit (p <
0.05). Sputum cultures were only 5% sensitive to ciprofloxacin and gentamicin,
but they were 100% sensitive to imipenem (p < 0.0001). Uncloaking imipenem was a
significant contributing factor in controlling this outbreak. Once outbreak
control measures were instituted, Acinetobacter isolates dropped from 77 (during
the outbreak year) to 9 (during the subsequent year) and no new pneumonia cases
occurred.
PMID- 9640036
TI - Perceptions of current and recent military internal medicine residents on
operational medicine, managed care, graduate medical education, and continued
military service.
AB - Current and recent internal medicine residents were surveyed on their level of
confidence in practicing operational medicine, satisfaction with graduate medical
education, the impact of TRICARE, the military managed care plan, on their
patients and education, and intentions on remaining in uniformed service. Their
sentiments were recorded on a five-point Likert scale (1 = strongly agree, 3 =
neutral, 5 = strongly disagree). Two hundred twenty-one of the 294 surveys were
returned (75.2%). Most physicians felt unprepared to perform duties in a nuclear,
biological, or chemical warfare environment, or handle administrative aspects of
operational medicine (mean scores, 3.2-3.7). A majority of respondents felt
satisfied with the quality of their residency experience (mean score, 1.9).
Although more than half of those surveyed (53.6%) listed the opportunity to teach
residents as a top factor influencing their retention decision, most felt
skeptical that graduate medical education would remain important in the future
(mean score, 3.6). Most physicians agreed that restriction of TRICARE to patients
less than 65 years old may degrade the quality of military internal medicine
residencies (mean score, 1.6). Previous service, Reserve Officer Training Corps
experience, and graduation from the Uniformed Services University of the Health
Sciences were factors associated with increased physician intention to remain
beyond their obligated service. The most common factors inducing physicians to
leave the military included frequent deployments, relocations, and financial
compensation. Factors cited most frequently as influencing physicians to stay on
active duty included high-quality colleagues, opportunities for teaching
residents, and freedom from malpractice and office management details.
PMID- 9640037
TI - Longitudinal trends and gender differences in physical fitness and lifestyle
factors in career U.S. Navy personnel (1983-1994)
AB - This study examines long-term health and physical readiness trends in the U.S.
Navy. We mailed lifestyle questionnaires to all participants in baseline studies
between 1983 and 1989 who were still on active duty in 1994. Commands provided
body composition and physical readiness test scores for the participants. Two
longitudinal cohorts were created: an 8-year sample (N = 640) with matched data
from 1986, 1989, and 1994; and an 11-year sample (N = 1,576), with data from 1983
and 1994. Analyses of both cohorts revealed significant improvements in
cardiovascular fitness, muscle strength, exercise, lean body mass, dietary
habits, and sleep, as well as significant decreases in tobacco and alcohol use
and job stress. However, hypertension rates, percentage of body fat, and body
mass index increased over time. Women's scores were significantly better than
men's on a number of factors. Overall, these findings suggest that the Navy's
health promotion efforts have had a significant positive effect on the fitness
and health behaviors of career Navy men and women.
PMID- 9640038
TI - Psychological aspects of pregnancy in the military: a review.
AB - OBJECTIVES: In the past 20 years, more women have joined the armed forces than
ever before. Consequently, the management of pregnant service members has raised
important medical and administrative issues. Recent studies comparing service
women with their civilian counterparts have shown a significantly increased rate
of pregnancy complications. This paper explores the psychosocial milieu in which
active duty pregnancies occur and attempts to elucidate the psychological
stressors that may contribute to the increased complication rate. METHODS: The
literature on pregnancy in the military and the existing regulations governing
its medical and administrative management are reviewed. Case material is
presented and analyzed. RESULTS AND CONCLUSIONS: Three types of psychological
stressors are identified and discussed: lack of social supports, the pressures of
minority status, and the institutional reactions to gender roles. The author
proposes mandatory education for military leaders regarding sensitivity to
women's reproductive issues as well as specialized briefings for women inductees
on the realities and risks of pregnancy in the military.
PMID- 9640039
TI - The field hospital at Zagreb: tri-service medical care in a peacekeeping
operation.
AB - The objective of this investigation was to provide military medical planners with
insights into the specific materiel, skills, and information requirements
demanded by humanitarian missions through review of approximately 16,000 records
from a tri-service medical patient database used at the field hospital in Zagreb,
Croatia, during Operation Provide Promise. This review describes (1) the origin,
rationale, structure, and implementation of the database; (2) the patients who
used medical services provided by the hospital; (3) the diagnoses encountered in
outpatient visits, admissions, and surgical operations; and (4) the distribution
of medical services used by various subgroups of interest.
PMID- 9640040
TI - Injuries in Croatian Army brigade soldiers inflicted in an offensive action
during the 1991/1992 war in Croatia.
AB - The type and number of injuries sustained by soldiers of a Croatian Army brigade
in an offensive action during the war in Croatia (1991/1992) were analyzed
according to the mechanism of wounding. About 1,000 soldiers participated in a 6
hour offensive action in a flat, partially swampy, and wooded area, convenient
for large-scale use of antipersonnel mines and other explosive devices. There
were 92 casualties in total: 15 soldiers were killed in action and 77 were
lightly or severely wounded. The mechanism of wounding included shell fragments
in 44 soldiers (47.8%), antipersonnel mines and gunshot projectiles in 14
soldiers each (15.3%), and others (fall, blow, stress, etc.) in 20 soldiers
(21.7%). Death was recorded in 1 of 13 soldiers (7.1%) with gunshot wounds, 11 of
44 soldiers (25%) wounded by shell projectiles, and 4 of 14 soldiers (28.5%)
wounded by antipersonnel mines. All injuries inflicted by shell fragments were
multiple, whereas the type and severity of injury inflicted by antipersonnel
mines were directly related to the type of mine. Pressure-activated mines
generally caused limited injuries to the lower extremities, ranging from
mutilation to amputation. Injuries inflicted by other antipersonnel mines
resembled those caused by shell projectiles; however, their severity depends on a
number of factors.
PMID- 9640041
TI - Clinical and radiological management of wartime eye and orbit injuries.
AB - OBJECTIVE: The purpose of this study is to present our experience in treating 191
patients with eye and orbit injuries that occurred during the war in Croatia and
Bosnia and Herzegovina. METHODS: The authors retrospectively reviewed the
clinical and radiological management of wartime eye and orbit injuries in
patients hospitalized at Clinical Hospital Split. RESULTS: Seventy-nine percent
of the war eye and orbit injuries were caused by fragments of explosive devices,
9.9% by high-velocity missiles, and 8.4% by other objects. Most of the patients
were admitted to the hospital within 24 hours of injury. The total number of
injured globes was 222; 48.2% of globes had intrabulbar (mostly magnetic) foreign
bodies, and 13% had extrabulbar intraorbital foreign bodies. Extensive wounds
(perforation, double perforation, rupture, and evisceration/ enucleation) were
encountered in 74% of patients, and 26% of patients had slight trauma. There was
a statistically significant correlation between admission within the first 12
hours and postoperative visual acuity (Chi 2 = 3.93; p = 0.0474). CONCLUSION:
Along with clinical examination, computed tomography is the most important
diagnostic procedure in preoperative evaluation of various forms of globe and
orbit injuries. The admission time is the most important factor in determining
postoperative visual acuity.
PMID- 9640042
TI - The Army psychological autopsy: then and now.
AB - The conduct and reporting of an Army psychological autopsy is a complex and
relatively infrequent event. The details of these reports may not be completely
clear to the behavioral sciences personnel tasked with collecting the data. This
paper reviews the current status of the Army psychological autopsy and contrasts
it with the development of civilian psychological autopsies. The current thinking
of the Department of Defense Health Affairs working group on psychological
autopsies is presented. The epidemiological content of the Army psychological
autopsy as a scientific resource is presented in the form of an analysis of the
psychological autopsies for the 1995 Army suicide data. Suggestions for updating
this unique command tool are included.
PMID- 9640044
TI - Shoulder arthroplasty in war wounds.
PMID- 9640043
TI - Hepatitis A and cytomegalovirus infection precipitating acute hemolysis in
glucose-6-phosphate dehydrogenase deficiency.
AB - A 34-year-old man presented with acute hemolytic anemia secondary to acute viral
hepatitis A and a coexisting acute cytomegalovirus infection. This association
has not been described previously in patients with glucose-6-phosphate
dehydrogenase deficiency and is the subject of this report.
PMID- 9640045
TI - [The study of the influence of aminoglycoside antibiotics on the hearing organs
in children].
AB - The paper presents results of audiologic assessments hearing examinations in 19
children that received aminoglycosides in cases of pneumonias, meningitis and
sepsis. Examination of hearing acuity with otoscopic assessment of the ears,
tympanometry, ABR and acoustic otoemission were performed before, directly after
infusion and after completion of treatment. After a laryngological examination
and of the hearing acuity, tympanometry and the ABR the authors have concluded
the normal state of the hearing organ. Only in the examination of the acoustic
otoemission produced during the treatment it was found the amplitude was
flattened or there was no otoeimssion for some individual frequencies in relation
to records taken before the treatment. The authors emphasize that among risk
factors of ototoxic effect of some medicines are of importance the following:
patient's age, uncontrolled increase in blood drug concentration, increase in
daily dosage, cumulation of the drug in the organism, prolonged treatment with
the drug.
PMID- 9640046
TI - [Dysphagia due to diffuse degenerative changes in the cervical spine].
AB - Degenerative changes in the cervical spine can produce osteophytes of the
anterior margins of the cervical vertebrae. Although cervical osteophytes have
been reported to cause many complications, most remain clinically silent. Very
few cases of pharyngeal dysphagia and pseudotumoral bulging of pharyngeal wall
resulting from cervical osteophytes have been described. Dysphagia in these cases
is caused either by mechanical obstruction or by paraoesophageal inflammation due
to irritation at the osteophytes processes. We present a case of 63 year-old
patient suffering dysphagia secondary to cervical osteophytes. ENT examination
reveal bulged wall of the hypopharynx resemble the tumor. The diagnosis was
established by conventional X-ray of the spine and CT. We investigated this case
fully to rule out an alternative pathology.
PMID- 9640047
TI - [Results of surgical treatment of laryngeal cancer in elderly patients in 1946
95].
AB - In the years 1946-1995 in Karol Marcinkowski University School of Medical
Sciences, Department of Otolaryngology, Head and Neck Surgery the long term
results on 2223 patients with laryngeal cancer treated surgically according to
the age were evaluated. Five year survival rates after total laryngectomy in
elderly persons was 44.2%. Five year survival rates (67.7%) after partial
laryngectomy justify their application in suitably chosen cases of cancer of the
larynx.
PMID- 9640048
TI - [The role of potential duplication of time for the neoplastic cells in patients
with head and neck cancer treated by radiation].
AB - Proliferation potential of tumour cells is one of the most important features of
malignant neoplasms. This factor can be assessed by measurement of the potential
doubling time (Tpot). This method includes the single intravenous injection of
thymidine analogue (iodo- or bromodeoxyuridine) with subsequent single biopsy of
the tumour and simple calculation using flow cytometry data of the specimen. The
preliminary results of clinical trials show that Tpot determined prior to
treatment can serve as an independent prognostic factor in patients with head and
neck cancer receiving conventional radiotherapy. This assay may also help to
selected a subgroup of patients with high proliferation capacity for whom
application of accelerated radiotherapy regimens may be advantageous. The aim of
this paper is to describe the methodology of Tpot measurement and to review the
clinical radiotherapy trials involving Tpot measurement.
PMID- 9640049
TI - [Selected parameters of immunologic reactivity in patients with sensorineural
hearing loss. I. Receptor activity of T lymphocytes].
AB - Receptors activity of peripheral T cells for sheep erythrocytes was analyzed in
67 healthy individuals and in the 29 patients with progressive, bilateral hearing
loss and in 7 patients with sudden deafness on unknown etiology. The ability of T
lymphocytes to form non-immune complete and incomplete rosettes in TEt and TEa
tests was evaluated before and at the beginning of ubiquitine therapy. The mean
values of rosette forming cells (RFC) in percentage and absolute numbers and the
statistical analysis were presented. It was found that the receptor activity of T
lymphocytes in TEt test was not significant different from the results of healthy
control group. On the other hand highly significant differences were observed (p
< 0.001) in subset of "active" T-cells determined in TEa rosette test. The
relative coefficient of receptor activity of lymphocytes (CRAL) calculated for
complete TEa rosettes was high different (p < 0.0008). Normalization of the
results of TE rosette tests after first period of ubiquitin biotherapy was
observed.
PMID- 9640050
TI - [The errors of the operative technique as a cause of unsuccessful tympanoplasty.
Part II].
AB - This study is based on the author's personal experience in a middle ear
reconstructions. Errors can occur at each surgical stage--tympanic membrane and
chain reconstructions, mobilisation of the footplate. At any moment the surgeon
can gain or loose the dB. The operating technique is the main factor. A proper
operative technic includes a good operating approach and excellent hemostasis.
The tympanic membrane, should be as thin as possible, exactly and carefully
dissected. Care should be taken to avoid any damage to the fascia graft fibers.
Bad or unsure material should be discarded. The graft should not be too large
because if it overlaps the EAC wall, it narrows the canal. If the graft is too
small, secondary edge performation can occur. The shallow placement of the graft
risk a bad contact. Opposite--too deep--poor ventilation of the middle ear and
may lead to adhesions. The annulus should be well prepared, free of epithelial
remnants. If not cholesteatoma could develop and discontinuity between the
neotympanium and the ossicular chain abolish the transmission effect. The
mechanical and lever principles during reconstruction of the sound transmission
should be kept in mind at all times. The reconstructed system must be delicate
and light. The round window reflex is the most important indice of good performed
reconstruction, and should be used similar to the modern monitoring system. Try
to prevent the natural structures. They are the most valuable material for the
future reconstruction.
PMID- 9640051
TI - [Laryngocele].
AB - Author present four cases of mixed laryngocoele. Planocellular carcinoma of
larynx was recognized at one of the four patients after 17 months from the
operation of laryngocoele. A rare case of bilateral laryngocoele described by the
authors was found in a woman, who was operated on in 1981 because of the internal
laryngocoele at the left side. She was reoperated in 1995 a mixed laryngocoele at
the right side was removed.
PMID- 9640052
TI - [Lobular capillary hemangioma of the nasal septum].
AB - A case of 27 years old woman cured surgically of lobular capillary hemangioma of
the nasal septum, which occurred post delivery was described. The current status
of this subject was presented.
PMID- 9640053
TI - [Prosper Meniere: unknown and little known facts].
AB - In the article some less known and unknown facts from Prosper Meniere's life are
reported. It was emphasized that in foreign bibliography etiology of Meniere's
disease isn't connected with labyrinthine's hameorrhagia, as it is often stated
in Polish laryngological literature.
PMID- 9640054
TI - [Organic nitrates--new perspectives on an old drug group].
PMID- 9640055
TI - [Current information on the metabolism of flavonoids. I. Absorption and
metabolism of flavonols].
PMID- 9640056
TI - [Thalidomide, an unending story].
PMID- 9640057
TI - [Lipoprotein metabolism disturbances in patients with kidney diseases].
AB - Lipoprotein(a) was discovered over 30 years age and it is an independent risk
factor for atherosclerosis, coronary artery disease and peripheral vascular
diseases. Among patients with end stage renal failure lipoprotein(a) levels are
higher than in general population and being independent of the type of treatment.
Cardiovascular diseases are the most important cause of mortality in ESRD
patients. Moreover we have interesting information about possibility of influence
of Lp(a) serum levels.
PMID- 9640058
TI - [The effect of pentoxifylline on treatment results and course of rehabilitation
of patients after ischemic stroke].
AB - The study has been taken up to compare the effect of treatment with
pentoxifylline and typical treatment in early ischaemic stroke. The study
included 107 patients aged 42-85, with the ischaemic stroke confirmed by CT scan,
in early stage of stroke (within 24 hours after onset). Excluded from the study
were patients with severe physical diseases. The patients were divided into two
groups. Group I was treated typically, group II had been profited from a typical,
appropriate therapy and pentoxifylline delivery during 30 days as well, with a
daily dose of 1200 mg i.v. within the first 5 days followed by an oral dose of
800 mg subsequent days. Such a treatment has been continued until 12th month. The
neurological state was assessed according to the European Stroke Scale (ESS) and
Mathew Scale (MS), general fitness according to the Kamofsky Scale (KS) and
Barthel Index (IB) at the admission, after 30 days and 12 months of the
treatment. Quality of life assessment using by Oxford Handicap Scale and Frenchay
Activities Index. After 30 days and 12 months of the treatment, no statistically
significant differences between all study groups was found in: 1) mortality, 2)
mean survival time, 3) neurological and functional state, 4) quality of life.
According to the above results the beneficial influence of pentoxifylline
treatment of ischaemic stroke was not confirmed.
PMID- 9640059
TI - [Evaluation of non-cerebral complications in light of ischemic stroke severity].
AB - Extracerebral complications which were observed in great number of ischemic
stroke patients increased the risk of death and disability. Pneumonia, myocardial
infarction, pulmonary embolisms and urinary tract infections are most often. We
considered the influences of extracerebral complications on anterior circulation
territory disturbances. A cohort of 1697 patients with first-ever ischemic stroke
within anterior circulation region was evaluated. Patients were divided into
three groups: A, B, C according to the heaviness of stroke. We understood the
heaviness of stroke as a degree of cerebral disfunction occurring within the
first 24 hours of the onset and assessed it using Clinical Groups of the Whole
Body Activity (CG WBM). CG WBM is an original classification, a three-degree one,
prepared by Department of Neurology University School of Medicine Sciences in
Bydgoszcz. The rate of complications was statistically significantly lower in
group A with the mild course of ischemic stroke than in group B with moderate or
in group C with the severe course of ischemic stroke. Pneumonia, myocardial
infarction and pulmonary embolism were recognized more often in patients with
fatal outcome. The amount of extracerebral complications raised with the severity
of the ischemic stroke.
PMID- 9640060
TI - [Evaluation of the prognostic value of general motor activity for rehabilitation
of patients after cerebral stroke].
AB - Following cerebral stroke motor activity of the patient is dependent on the
extensiveness of brain ischemia. Evaluation of this activity may be an exponent
of brain ischemia extent. It can be used for the determination of predictability
of patient survival and results of rehabilitation. Using Mathew and Barthel
scales effectiveness of treatment and rehabilitation was evaluated four times
during 12-month follow-up in patients of General Motor Activity Clinical Group II
i III. The results obtained may be evidence of significant prognostic importance
of evaluation of general motor activity of the organism in the initial period of
treatment and rehabilitation only, i.e. within 3 months following cerebral
stroke. However, it is no importance for evaluation of remote results (one year
following cerebral stroke). The evaluation of general activity cannot be used to
predict the dynamics of the improvement of neurological and functional status of
patients undergoing rehabilitation following cerebral stroke.
PMID- 9640061
TI - [Concentrations of tumor necrosis factor alpha and interleukin-1 beta in
cerebrospinal fluid in the course of tick-borne encephalitis].
AB - CSF concentrations of TNF-alpha and Il-1 beta were detected in patients with TBE.
The cytokines were detected by immunometric assay by MEDGENIX kit. CSF
Concentrations of TNF-alpha and IL-1 beta in patients with TBE were significantly
higher than in control group before as well as after treatment and normalization
of CSF parameters. These concentrations were lower comparing to one obtained in
group of bacterial meningitis. There was no correlation between concentration of
cytokines and other CSF parameters (cytosis, protein, glucose concentration).
Concentrations of analysed cytokines did not change significantly before and
after treatment. Detection of CSF concentrations of TNF-alpha and Il-1 beta in
patients with tick-borne encephalitis can be used to evaluate efficacy of
treatment and retreat of infection.
PMID- 9640062
TI - [Allogenic blood stem cell transplants: characteristics of transplantation
material and clinical transplantation course].
AB - We have analysed the clinical course of the 14 consecutive allogeneic peripheral
blood stem cell transplantations (PBSCT) and cellular composition of the grafts.
Donors were HLA-identical siblings except for the one donor who was only HLA
phenotypically identical brother. Nine of them were sex-mismatched to their
recipient. Donors received filgrastim (G-CSF) at a dose of 10 microkilograms/kg
for 5 days (4-6). Leukaphereses were started at 5 day to obtain the target dose 4
x 10(6) CD34+ cells/kg recipient weight. Median 24 l of blood (24-36) was
processed collecting: 10.3 x 10(8)/kg (6.69-18.8) WBC, 9.9 x 10(8)/kg (5.87
16.02) MNC, 9.72 x 10(6)/kg (0.74-18.98) CD34+ cells, 242.5 x 10(6)/kg (77.9-422)
T lymphocytes (CD4+ to CD8+ ratio was 1.5), 76 x 10(6)/kg (24-113) B lymphocytes,
33 x 10(6)/kg (14-88) NK cells and 168.8 x 104/kg (23.1-271.4) CFU-GM with 131.7
x 10(4)/kg (8.4-297.6) BFU-E. Engraftment times to a neutrophil count (ANC) > 0.5
x 10(9)/l was achieved at a median of 15 days (range 10-23) in all patients
whereas the platelet count > 20 x 10(9)/l at a median of 14 days (9-19) in all
but one patient who received the smallest dose of CD34+ cells. Acute graft versus
host disease (GvHD) developed in 8 patients who survived more than 30 days. Most
of them (75%) were patients with chronic myeloid leukaemia (CML). In 4 of them
GvHD was steroid resistant. Chronic GvHD developed in 3 of 6 evaluable patients.
We confirm that allogeneic PBSCT result in rapid and longterm trilineage
engraftment. However, the observation of the increasing incidence and severity of
acute GvHD in patients with CML will require verification in the larger setting
of patients after completion of ongoing clinical trials.
PMID- 9640063
TI - [The role of chemotherapy in treatment of nephroblastoma in children. Report of
the Polish Pediatric Group re. treatments of solid tumors].
AB - Retrospective analysis of chemotherapy results of children with nephroblastoma
was performed in 220 patients aged from 1 yr to 14 yrs of live in 12 centers.
Stage I nephroblastoma was documented in 24.5% but stage II--in 55.3%.
Histologically 74.6% cases were diagnosed as medium malignant and 12.7%--high
malignant. Therapy results were similar to observed in other centers.
PMID- 9640064
TI - [Results of treating patients with highly malignant non-Hodgkin's lymphomas;
comparison of treatment efficacy with CHOP and CBVPM-AVBP].
AB - The treatment of highly of 43 patients with highly malignant non-Hodgkin
lymphomas were analysed and assessed. These patients were treated at the
Department of Hematology, Pomeranian Medical Academy within 1981-1990. The
process was advanced in 76% of and localization of the tumour outside lymph nodes
was also seen in 79%. The results of treatment with CHOP regimen used during the
first 5 years were compared with CBVPM-AVBP used in 1986-1990. CBVPM-AVBP regimen
proved more 4 effective (55% of the complete remissions) than CHOP regimen (37.5%
of the complete remission). Mean duration of the complete remission (survival
free from the relapse) was 27.5 (1-88) months. Complete remissions were easier to
achieve in patients with centroblastic lymphoma in higher percentage. These
patients survived longer than those with other highly malignant lymphomas. The
authors conclude that further intensification of chemotherapy in case of highly
malignant non-Hodgkin lymphomas is justified.
PMID- 9640065
TI - [Evaluation of the usefulness of stereotactic aspiration fine needle biopsy for
breast neoplasm diagnosis in the preclinical stages].
AB - Out of 6000 mammographies performed in the years 1991-1992, 61 patients have been
qualified to stereotactic fine needle biopsies. Finally 50 stereotactic biopsies
have been performed on 37 patients. In 6 cases (12%) cancer has been recognized.
Stereotactic biopsy allows to recognize cancer in preclinical stages. In
comparison with the surgical this method is less stressing for the patients and
cheaper.
PMID- 9640066
TI - [Storage of human bone marrow before transplantation at 4 degrees C. The effect
of cell proliferation potential particularly in hematopoietic cloned cell lines].
AB - The possibility of storage of human bone marrow CD34+ cells at 4 degrees C for
bone marrow transplantation purposes was investigated. The cells were placed in
Iscove medium supplemented with 20% serum (15% bovine calf serum + 5% human AB
serum) for three weeks at 4 degrees C. During storage time clonogenicity of
granulocytic-monocytic (CFU-GM) erythropoietic (BFU-E) and megakaryocytic (CFU
Meg) progenitors were investigated. It turns out that it is possible to keep
human CD34+ cells at 4 degrees C for at least few days before transplantation. At
day four of storage the number of CFU-GM and BFU-E cells still exceeded 50% of
cells present at day 0. We have found however, CFU-Meg progenitors in comparison
to others are much more sensitive to metabolic storage stress. This enhanced
sensitivity of megakaryocytic progenitors could explain at least partially the
well known ++phenomenon of retardation of thrombopoietic recovery in patients
undergoing bone marrow transplantation.
PMID- 9640067
TI - [Social problems of porphyria].
AB - Late consequences of the attacks of acute porphyrias were studied. Among 312
patients who were investigated the motor disability (neuropathy) was found in 9
patients, psychoneurological changes in 1 case and drug abuse in 7 subjects. In
the group of 200 patients in remission (chosen at random) 72 persons (36%)
received a disability pension. The existence of problems in change of the
profession when it was necessary for health-reasons was marked. It was find that
Dolargan (Pethidine) is too often applied to the patients in remission. It was
made the warning that drug dependence will arise very easy in patients with
porphyria.
PMID- 9640068
TI - [Evaluation of sweating function, changes in heart function and postural blood
pressure in patients with multiple sclerosis].
AB - The aim of the study was electrophysiologic assessment of sudomotor function and
some aspects of cardiovascular system function in patients with multiple
sclerosis and an attempt of referring assessed variables to duration of the
disease and EDSS score. The study included 24 patients with clinically definite,
relapsing-remitting multiple sclerosis and 22 healthy, age-matched controls.
Autonomic functions were evaluated by means of clinical examination, heart rate
variability tests, measures of blood pressure in supine and standing position and
skin sympathetic response examination. Clinical symptoms in patients with
multiple sclerosis were scarce. Electrophysiologic tests showed no abnormalities
in heart rate variability and blood pressure response to standing in studied
group. The majority of patients presented with subclinical dysfunction of
sudomotor system, indicated by an abnormal sympathetic skin response, which did
not correlate with duration of the disease or EDSS score. Sympathetic skin
response examination proved to be a sensitive indicator of autonomic disturbances
in patients with multiple sclerosis.
PMID- 9640069
TI - [Use of hypoprothrombinemia provocation test for early diagnosis of liver disease
caused by harmful environmental agents].
AB - The aim of this work has been to assess the feasibility of using Prothrombin Time
(PT) Assay before and after administration of Pelentan (Hypoprothrombinemia
Provocation (HPP) Test) for early detection of subclinical toxic hepatic
injuries. The proposed modification of PT Assay is based on the observation that
people with slight hepatic injury receiving small doses of Pelentan
(diethylcoumarol) display remarkably longer PT than healthy people receiving
similar doses of the chemical. The test group comprised 37 people occupationally
exposed to hepatotoxic agents, 85 males permanently abusing alcohol, while 24
clinically healthy people, not exposed occupationally to the toxic agents served
as the control. In addition, 26 hepatitis B and/or C virus carriers were also
examined. The results show that: 1. HPP test enables assessment of hepatic
function in patients with suspected hepatic injury and in people permanently
abusing alcohol; 2. low value of serum prothrombin index 24 h and 48 h after the
administration of Pelentan is indicative of the positive result of the test; 3.
HPP test provides more information on the functional condition of liver than
single PT determination by the Quick assay.
PMID- 9640070
TI - [Evaluation of efficacy and tolerance sumatriptan at a dose of 50 mg in treatment
of migraine attack].
AB - Sumatriptan has been used successfully in the acute treatment of migraine since
1991. Most patients (70-80%) experience pain relief 2-4 hours after receiving 100
mg sumatriptan orally. During last few years efficacy of lower doses has been
studied. Many authors proved that 50 mg of sumatriptan may be as effective as 100
mg. Our study confirmed that 50 mg oral dose of sumatriptan is sufficient in many
patients. Headache relief was achieved in 58% of treated patients after single
dose. The second dose of sumatriptan was effective in next 14% of patients.
Totally headache relief after two doses of sumatriptan was achieved in 72% of
patients. The sumatriptan 50 mg was well tolerated; only 10% of patients reported
adverse events, which were minor and transient.
PMID- 9640071
TI - [Hereditary cerebellar ataxia syndrome].
AB - Hereditary cerebellar ataxia syndrome has been described in 68 yrs old man with
progressive symptoms of muscle disturbances of lys. Next other clinical symptoms
were observed.
PMID- 9640072
TI - [Treatment problems of eosinophilic granuloma].
AB - Two clinical cases of eosinophilic granuloma with pulmonary manifestation were
observed. Therapeutical problems were discussed and corticosteroids and
cytostatics were recommended.
PMID- 9640073
TI - [Diagnostic difficulties with skull and brain injury complications in alcoholic
patients].
AB - About 20% of patients treated because of craniocerebral injuries are those after
an alcohol intake. Great number of these patients slightly bodily injured without
any focal cerebral deficit are stopped by police. The effects of injuries masked
by the picture of alcohol intoxication are developed during that time. Published
data and authors of this paper observations show that atypical clinical picture,
lack of typical, specific disturbances of cerebral function make diagnosing of
the effect of craniocerebral injuries difficult. To avoid diagnostic errors in
inebriate patients with head injuries, the degree of cerebral function
disturbances together with life-threatening risk factors should be carefully
evaluated. Afterwards the range of diagnostic methods can be established. If the
wide range of diagnostics is not necessary, patients should be observed over the
period of a few hours. The authors present original 63-points Scale of Brainstem
Insufficiency (ITC). This ITC scale assesses: consciousness, the whole body
movements, vegetative functions (breath temperature, blood pressure, pulse),
pupils and eye movements movements. This scale can be used for evaluation of
global cerebral function disturbances observed in not only craniocerebral
injuries but in alcohol intoxication as well.
PMID- 9640074
TI - [The role of nutrition on the treatment of septic syndrome and multiple organ
failure].
AB - Basing on current literature the issues regarding nutrition in patients with
septic syndrome and multiple organ failure were discussed. It was emphasised that
patient feeding along with providing metabolic substrates also serves as a
treatment method. Diet ingredients in specific carbohydrate, protein and fat
metabolism disorders were analysed. We focused upon the role of emulsion of fat,
especially medium chain triglycerides (MCT) and -3-linolenic acid (fish oil). The
unique role o f glutamine, arginine and branched chain amino acids (BCA) was
highlighted. Patient nutrition with accordance to the presented new methods has
become an efficient routine of treatment in septic syndrome. It may constitute an
efficient prophylaxis against multiple organ failure.
PMID- 9640075
TI - [Management of pancreatic injury].
PMID- 9640076
TI - [Kava-kava preparations--alternative anxiolytics].
AB - Since Cook's world cruises (1772-1775) there is written evidence of the use of
kava-kava by the inhabitants of the Pacific Islands. In last decades kava-kava,
an extract of the plant Piper methysticum was used in several European countries
(drugs like Laitan, Antares, Viocava, Mosaro etc.). In the presented paper the
authors describe the pharmacology, toxicology and pharmacokinetics of the active
compounds of kava-kava the kavapyrones. The discussion concerning the therapeutic
value of kavapyrones ends with the conclusion of the authors, that kava-kava may
be a useful alternative for synthetic anxiolytics.
PMID- 9640077
TI - [Urinary excretion of extracellular matrix proteins in insulin dependent diabetes
mellitus].
AB - The purpose of the study was to assess urinary excretion of extracellular matrix
proteins and proteolytic enzymes in 12 subjects with IDDM with albuminuria, 12
subjects with IDDM without microalbuminuria and 10 normal healthy subjects.
Urinary excretion of FN was significantly higher in subjects with IDDM and
albuminuria as compared to patients with IDDM without microalbuminuria and
healthy subjects (223.6 +/- 143.2 vs. 103.2 +/- 59.7 vs. 58.3 +/- 12.0 ng/mg
creatinine, p < 0.01). Urinary level of type IV collagen was significantly
elevated in subjects with IDDM and albuminuria as compared to IDDM without
microalbuminuria and healthy subjects of cathepsin B was significantly higher in
diabetic patients with albuminuria as compared to patients without
microalbuminuria and healthy subjects (0.82 +/- 0.53 vs. 0.25 +/- 0.17 vs. 0.22
+/- 0.05 mlU/mg creatinine, p < 0.01). Urinary activity of plasmin was
significantly elevated in diabetic patients with albuminuria as compared to
subjects without microalbuminuria and healthy control (0.477 +/- 0.37 vs. 0.194
+/- 0.09 vs. 0.21 +/- 0.02 mlU/mg creatinine, p < 0.01). Our data indicate that
increase in the urinary excretion of extracellular matrix proteins may be the
useful tool for monitoring glomerular injury.
PMID- 9640078
TI - [Mutation T-->C of nucleotide 2238 in the gene of atrial natriuretic peptide
(ANP) precursor and heterogeneity of sodium-sensitive hypertension. Preliminary
report].
AB - Atrial natriuretic peptide (ANP) is involved in the pathogenesis of sodium
sensitive hypertension. The loss of Sca I restriction site in the ANP precursor
gene abolishes the regular stop codon. The aim of our study was the analysis of
the Sca I gene polymorphism in 23 patients with sodium-sensitive hypertension,
the molecular characteristic of the mutation and the comparison of the blood
pressure values, plasma renin activity, plasma ANP and aldosterone concentration
between patients with or without mutation. Applying the polymerase chain reaction
(PCR), followed by digestion with Sca I, the heterozygous mutation has been found
in 9 (39%) patients. The sequencing of PCR products indicated that the loss of
Sca I restriction site is caused by T2238-->C transition leading to the
translation of ANP with two additional arginines. The higher concentration of ANP
in plasma has been found in T2238-->C transition patients on normal and high
sodium diet as compared with patients without mutation. These preliminary results
suggest that the heterogeneity of sodium-sensitive hypertension is associated
with the T2238-->C mutation of the ANP precursor gene.
PMID- 9640079
TI - [Evaluation of platelet function and tissue plasminogen activator activity in
ischemic heart disease depending on concurrence with hyperlipoproteinemia and
aspirin therapy].
AB - Platelet activation, impairment of fibrinolysis and dyslipidemia are important
factors in the pathogenesis and progression of ischemic heart disease. Aspirin
therapy will reduce platelet activation both by its negative effect on platelet
aggregation (SPA) and by inhibition of granule release which liberates such
mediators as platelet factor 4 (PF4) and plasminogen activator inhibitor 1 (PAI
1). The present study was performed in 57 patients with ischemic heart disease
(IHD), divided into groups depending on coexistent hyperlipoproteinemia (HLP) and
aspirin treatment. The control group included 21 healthy individuals, matched for
age and sex. Parameters of hemostasis (SPA, PF4, PAI-1) and concentration of
lipid fractions (TC, TG, LDL, HDL) were measured in plasma. Increased PF4 levels
were found in all groups with IHD, irrespective of hyperlipoproteinemia or
aspirin treatment. Enhanced SPA and higher PAI-1 were limited to group IHD-HLP
without aspirin. Highest PAI-1 activities were observed after stimulation of
platelets in vitro. In conclusion, patients with IHD and hyperlipoproteinemia
presented most pronounced platelet activation and impairment of fibrinolysis.
Aspirin had a beneficial effect on these changes. Lower activities of PAI-1, in
patients treated with aspirin, can be ascribed to its reduced release from
platelets. Aspirin did not satisfactorily reduce the level of PF4, although it
strongly inhibited SPA.
PMID- 9640080
TI - [Zinc protoporphyrin (ZPP) in diagnosis of anemia].
AB - In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and
the ZPP concentration in erythrocytes increased (normal value < 2.3 micrograms
ZPP/g Hb). The ZPP level and comparison with the other normally used tests in
iron deficiency in the group of the patients with iron deficiency, ACD, MDS, AML,
plasmocytoma was investigated. The ZPP level was determined by hematofluorometry
in samples from 96 patients. Thirty five patients with iron depletion showed
decreased both serum ferritin (median 5.9 ng/ml), and hemoglobin level (median
9.8 g/dl) with significantly increased ZPP level (median 8.5 micrograms/gHb). An
increased level of ZPP (median 3.95 micrograms/gHb) with normal level of ferritin
(median 24 ng/ml) and iron (median 50 (g/dl) in the serum of patients with ACD
was determined. Measurement of ZPP level in the combination with ferritin and
peripheral blood morphology allows to classify the degree of iron deficiency. The
ZPP levels higher than 4.55 micrograms/gHb confirms iron deficiency in the group
of anaemic patients.
PMID- 9640081
TI - [The influence of salmon calcitonin on the soluble form of VCAM-1 (CD 106) and E
selectin (CD 62E) in serum of patients with atopic bronchial asthma].
AB - The aim of the study was to evaluate the effect of salmon calcitonin (CT) on
serum level of soluble form of VCAM-1 (sVCAM-1 = soluble vascular cell adhesion
molecule-1) and E-selectin (sE-selectin = soluble E-selectin) in patients with
atopic bronchial asthma. Twenty-four individuals divided into 4 groups (6 persons
each) were investigated. The first group consisted of patients with chronic
moderate bronchial asthma, the second and third groups consisted of patients with
mild bronchial asthma and the fourth group K consisted of healthy individuals.
The patients of the first and second group were treated with CT at a dose of 100
i.v./days s.c. for three days. The patients of the third group were given placebo
(phychological saline) in similar way as CT. The indices were measured before the
treatment with CT or placebo and on the 4th day of the treatment. It was found
that CT treatment decreased sVCAM-1 in serum only in the patients of the first
group (p < 0.05) but had no effect upon sE-selectin level. The obtained results
suggest that CT interfered into mechanisms of inflammation involving adhesion
molecules in patients with bronchial asthma.
PMID- 9640082
TI - [Renal proximal disfunction based on activity of n-acetyl-beta-d-glucosaminidase
in urine of patients with kidney failure].
AB - N-acetyl-beta-D-glucosaminidase (NAG) urine activities of 63 patients with stable
and unstable chronic renal failure have been investigated. The values of NAG
activity obtained from these patients were compared with NAG activity of 33
normal controls. Abnormal NAG values (> 70 nmol/mg of creatinine) were found in
60 (95.2%) patients with chronic renal failure and the median of all values was
327.8 nmol/mg of creatinine. It was 14-fold greater than the median of values for
normal controls. There were any significant differences of NAG values between the
patients with massive proteinuria (> 1.5 g/24 h), moderate proteinuria and those
without 24 hour proteinuria or non-significant proteinuria (respectively 423.5 +/
286.3 vs 414.4 +/- 334.8 vs 453.0 +/- 451.3 nmol/mg of creatinine). There was no
significant difference between the two subgroups of patients with NAG values
above and below 280 nmol/mg of creatinine in age, gender, serum urea and uric
acid levels. However, the incidence of patients with NAG values higher than 280
nmol/mg of creatinine was statistically significant in unstable course of renal
insufficiency and raised serum creatinine levels. It is suggested that the
measurement of NAG excretion may be helpful to monitor unstable process in renal
failure.
PMID- 9640083
TI - [Liver failure in the course of Wilson's disease--report of two cases].
AB - Wilson's disease is an autosomal recessive disorder characterized by inability to
excrete copper, and manifests by hepatic, neurologic or/and psychiatric symptoms.
The therapy is available if diagnosis is made in time. The hepatic form of the
disease is rarely recognized in Poland. The authors describe two patients with
Wilson's disease who developed acute hepatic failure leading to death, in the
first case within few months, in the second within few weeks. The diagnosis was
established in the terminal stage of the disease and attempts of treatment were
uneffective.
PMID- 9640084
TI - [Fibromuscular dysplasia of the internal carotid artery as a cause of transient
cerebral ischemia episodes].
AB - A case of fibromuscular dysplasia affecting internal carotid artery is described.
It is presented clinically as repeated episodes of transient monocular blindness
on the affected side. We discuss clinical, pathological, color doppler and
angiographic findings characteristic for this type of pathology.
PMID- 9640085
TI - [Noninvasive diagnosis of extracranial and peripheral artery diseases].
PMID- 9640086
TI - [The influence of physiopathologic and genetic factors on drug
biotransformation].
PMID- 9640087
TI - [Uremic pruritus--pathogenesis and treatment].
PMID- 9640088
TI - [Beta-adrenolytic drugs in heart failure--hopes and reality].
PMID- 9640089
TI - [Endoral donor bone removal for autografts. A comparative clinical study of donor
sites in the chin area and the retromolar region].
PMID- 9640090
TI - [Universal building cable installation in the dental practice].
PMID- 9640091
TI - Predicting extreme patterns of long-term course of psychogenic impairment: a ten
year follow-up.
AB - This longitudinal study identifies predictors of course and etiologically
relevant factors of psychogenic disorders. Since 1979, the Mannheim Cohort
Project on the Epidemiology of Psychogenic Disorders has investigated neurotic
spectrum disorders, personality disorders, stress reactions, and somatoform
disorders in the normal population. Using these data, a cohort of probands
suffering from moderate psychogenic impairment (N = 240; 121 men, 119 women)
based on a representative sample of the urban adult population (N = 600; with
cohorts 1935, 1945, 1955; gender distribution 1:1) of Mannheim, an industrial and
university town in Germany, was followed up for almost 10 years. The cohort was
investigated three times by psychodynamically trained physicians and
psychologists. Tests were performed by means of cluster analysis. Different types
of course of psychogenic impairment were identified. Both extreme types--the
probands with the most positive and the most negative spontaneous long-term
course--were investigated with regard to potential course-determining variables.
Personality variables and conditions of early childhood development considerably
influenced the spontaneous long-term course.
PMID- 9640092
TI - Accessibility of government-run sheltered workshops to people with psychiatric
histories.
AB - Government-run sheltered workshops in the Netherlands are not as easily
accessible to people with psychiatric histories as they are to other groups, such
as those with physical and intellectual disabilities. This was found in a large
scale nationwide study in 21 such workshops, commissioned by the Dutch Ministry
of Social Affairs and Employment. The workshops varied in their degree of
accessibility. The more accessible ones placed stronger emphasis on social
objectives and had shorter waiting periods and more lenient admission policies.
PMID- 9640093
TI - Detecting errors in a scoring program: a method of double diagnosis using a
computer-generated sample.
AB - This paper discusses a new method for locating errors in diagnostic computer
scoring programs for structured clinical interviews. It was proposed as a test of
the accuracy of the scoring program for the Composite International Diagnostic
Interview, version 1.1. The proposal was to create an independent scoring program
in a different computer language but serving the same criteria. Both programs
were then applied to the same large set of valid (i.e., logically consistent)
computer-generated test cases, and differences in diagnostic assignments
reviewed. The method described can identify the program steps that account for
the sources of the errors. Corrections can be made and the programs run again on
new sets of test cases until discrepancy-free results are achieved. While this
method cannot discover errors that are repeated in the two programs, it does
discover more of the errors in a scoring program than we have previously been
able to identify. This technique provides a systematic and rigorous approach to
assuring the accuracy of scoring programs based on established algorithms.
PMID- 9640094
TI - Symptom distress and frequency of life events.
AB - A study of the frequency of life events was conducted in a group of subjects
selected from the general population over a period of 9 months. Four assessments
were made, using an events questionnaire and the Psychiatric Symptom Index (PSI),
at 3-monthly intervals. The results show a significant relationship (maintained
over time) between PSI score and the number of upsetting events, but no
significant relationship between PSI score and non-upsetting events. These
observations are interpreted as follows: the higher frequency of upsetting life
events is secondary to the previous psychological pattern of subjects.
PMID- 9640095
TI - Psychiatric disorder and disability in a rural community.
AB - This study examined the relationship between psychiatric disorder and disability
in a rural community and the use of formal and informal services in the
management of such disabilities. It was found that of the 26% of the surveyed
population who obtained a positive current psychiatric diagnosis, 48.3% had
required assistance in managing at least one activity of daily living. The
majority of those seeking assistance in managing these functional problems did so
from family and friends rather than from formal agencies. Psychiatric disorder
was found to lead to disability as frequently as did physical disorder, with
almost 50% of those who had experienced mental health problems reporting that
they were currently unable to carry out at least one activity of daily living.
The finding that assistance was sought primarily from family and friends raises
important questions about the nature of psychiatric disorder as a public health
problem.
PMID- 9640096
TI - Arrest among psychotic inpatients: assessing the relationship to diagnosis,
gender, number of admissions, and social class.
AB - The present study of psychotic patients investigates the relationship of specific
psychotic diagnoses (i.e., psychoactive-substance-induced psychosis,
schizophrenia, bipolar disorder, other DSM-III Axis I psychotic disorders),
social class, gender, and number of admissions to the rate of arrest in the
community. All admissions with psychotic symptoms to hospitals providing
inpatient psychiatric services in the Baltimore area were surveyed during a 6
year period. Study participants were assessed using a modified version of the
Diagnostic Interview Schedule. During the course of the interview, patients were
asked whether they had ever been arrested as a juvenile or as an adult. After
adjusting for age, gender, number of admissions, and social class, we found that
patients admitted for psychoactive-substance-induced psychosis were more likely
to report having been arrested than patients with other psychotic diagnoses.
Patients with schizophrenia were not more likely to have an history of arrest
than patients with other psychotic disorders. Number of admissions and social
class were independent predictors of history of arrest. The relationship between
psychotic diagnosis and history of arrest was modified by gender. Psychotic
patients with substance-induced diagnosis who were male were more likely to
report a prior arrest in the community than their female counterparts. Our
results suggest that type of psychotic diagnosis and social class, in addition to
gender and number of admissions, are important predictors of differences in
arrest-rate histories among psychotic patients. Gender appears to be an effect
modifier of the relationship between psychotic diagnosis and history of arrest.
PMID- 9640098
TI - Factors related to utilization of services for mental health reasons in Montreal,
Canada.
AB - This study examines factors related to the utilization of services for mental
health reasons by Montreal residents. Data were drawn from telephone interviews.
A random sample of 893 respondents completed a questionnaire on service
utilization and the Diagnostic Interview Schedule Self Administered to assess DSM
III-R psychiatric disorders. Results indicate that 12.8% of the population had
used such services in the past year. Medical doctors and psychiatrists, whose
services are free of charge under universal health coverage, were consulted,
respectively, by 4.1% and 2.0% of respondents. Psychologists, whose services are
not free, were seen by 3.4% of respondents. In all, 42.0% of respondents who
presented a current diagnosis used services in the past year. The highest
proportion of users (48.0%) was found among respondents who presented both
current and lifetime diagnoses and among respondents with comorbidity. The choice
of caregiver was related also to pattern of disorders: respondents with current
and comorbid disorders tended to consult general practitioners, while respondents
with lifetime disorders or with lifetime and current disorders favoured
specialized care. In line with other studies, self-perception of mental health,
gender and marital status were related to utilization; unlike other studies,
attitudes and age were not. It is argued that particularities found in this study
stem not only from methodological considerations, but also from the configuration
of the mental health system in Quebec, where the greater availability of
psychologists may facilitate service utilization.
PMID- 9640097
TI - Prevalence estimates of cognitive impairment in medical model adult day health
care programs.
AB - Despite an increasing emphasis on adult day health care (ADHC) programs as
alternatives to institutional care for persons with dementia, little research
based on direct assessment of clients' cognitive status has been conducted in
such settings. The goal of this analysis was to estimate the prevalence of
cognitive impairment among ADHC clients using commonly used screening measures.
Age-adjusted and non-age-adjusted prevalence estimates of cognitive impairment in
New York State ADHC programs were developed using a probability sample of 336
clients. Estimates were made using traditional cutting scores on standard
cognitive screening measures, such as the Mini-Mental State Examination (MMSE),
as well as latent class analyses applied to the same item sets. Average
prevalence estimates of cognitive impairment were 55% across age cohorts and 60%
for persons aged 65 and over. The MMSE yielded a prevalence estimate of 58%
across age cohorts and 63% for those aged 65 and over. Using a more conservative
cut score, the estimate for the MMSE was 33%; latent class estimates of moderate
to severe impairment indicate that approximately 30% of the ADHC clients had
cognitive impairment suggestive of probable or definite dementia. Community
alternatives to institutional care for the elderly are increasing in popularity.
These findings suggest that 1. While institutions are serving the most severely
cognitively impaired, age-adjusted prevalence ratios for the ADHC sample approach
the bounds of the institutional estimates. 2. The institutional setting will
continue to be an important mode of care for the more severely impaired
individuals. 3. Daycare is serving a high proportion of the mildly and moderately
cognitively impaired individuals. It follows, therefore, that such programs need
to address the needs of these individuals by developing specialized care plans
and tracks targeted for the cognitively impaired.
PMID- 9640099
TI - Experimental infection with Ehrlichia phagocytophila in cattle.
AB - Twenty Norwegian Red cattle, aged 8-10 months were used. Ten animals were
inoculated intravenously with 3 ml of a whole blood dimethyl sulphoxide stabilate
of a bovine strain of Ehrlichia (Cytoecetes) phagocytophila. The animals were
observed on a daily basis for clinical symptoms and rectal temperatures were
recorded daily for 36 days post inoculation. Blood and serum samples were
collected regularly during the observation period. All infected animals developed
fever of 2-4 days duration within a week. Six out of 10 animals had secondary
temperature rises of 1-2 days duration. Three animals showed swellings in the
hind limbs and a stiff gait. Compared with the control group, there was a 10%
decrease in the mean haematocrit and a leukopenia that initially was due to a
lymphopenia and later to a neutropenia. A monocytosis occurred after the
subsidence of the primary fever period. A thrombocytopenia occurred during the
early phase of infection. Granulocytic inclusions were detected for 18-32 days.
All infected animals developed antibodies > or = 1:4096 to E. phagocytophila
within 14 days post infection.
PMID- 9640100
TI - Epidemiological aspects of dermatophyte infections in horses and cattle.
AB - Ringworm infections in the principal domestic animals are a major public and
veterinary health problem. The aetiology, epidemiology and symptomatology of
these mycoses are quite heterogeneous and complex. In this context, the AA
carried out an epidemiological study to investigate the prevalence of
dermatophytes in two different animal species, horses (n = 200) belonging to 10
private stables and cattle (n = 1900) belonging to farms with different breeding
purposes and management. With regard to horses the results showed a positive
level of 9% and Trichophyton equinum was the major organism isolated. The results
concerning the cattle showed positive values that varied both in relation to the
type of animals and their management as well as to the productive objectives: 19%
in intensive beef breeding, 4.5% in intensive dairy farms (the aetiologic agent
isolated in both types of farms was Trichophyton verrucosum) and 8% in
traditional-type farms (the species of fungi isolated were T. verrucosum and
Trichophyton mentagrophytes). The results are discussed both in clinical and in
hygiene and management terms.
PMID- 9640101
TI - Serological studies on Corynebacterium pseudotuberculosis infections in goats
using enzyme-linked immunosorbent assay.
AB - Corynebacterium pseudotuberculosis was isolated from a goat suffering from
caseous lymphadenitis and used for preparation of cell wall antigens and exotoxin
for detection of specific antibodies in enzyme-linked immunosorbent assay
(ELISA). In immunoblotting sodium dodecyt sulphate (SDS) extracted cell wall
antigens revealed molecular weights ranging from 20 to 120 kDa. The raw exotoxin
showed molecular weights of 30 and 55 kDa and an inhibition of the haemolysis of
a Staphylococcus aureus strain. For validation of the ELISA 109 goats of known
clinical status were examined reaching a sensitivity of 96% and a specificity of
76% for this test. No serological reactions showed in 191 goats originating from
11 flocks which never had suffered from caseous lymphadenitis. Using this ELISA
test 24 goats originating from flocks suffering from caseous lymphadenitis were
examined serologically before and after vaccination with a bacterin. Before
vaccination one of the five goats with clinical signs showed no positive reaction
in ELISA. After vaccination all 24 animals showed positive reactions. Of a total
of 1868 goats sampled in Baden-Wuerttemberg 41 (2.2%) in 22 (10%) flocks showed
positive reactions in ELISA.
PMID- 9640102
TI - Assaying granulocyte phagocytosis by chemiluminescence: effect of storage time
and temperature of blood samples.
AB - The objective was to study the effect of storage of blood samples for up to 4.5 h
at either room temperature or on ice on granulocyte phagocytosis as assessed by
chemiluminscence. The study included three groups of animals: eight pigs, seven
cows and eight horses, which were bled at one occasion. The blood samples were
divided into two and stored either at room temperature or on ice. Granulocyte
phagocytosis in the samples was then assessed every 60 min starting 30 min and
finishing 4.5 h after bleeding. The phagocytosis was recorded as the AUC of
chemiluminescence following phagocytosis of opsonized zymosan particles. The time
of storage of blood samples had a significant (P < 0.001) overall effect on the
chemiluminscence following phagocytosis in all species tested, as was the case
with storage temperature (P < 0.001). It should be noted, however, that there
were considerable species differences in the effect of the storage on the
granulocyte phagocytosis. Hence, for valid comparisons of data on granulocyte
phagocytosis assessed by chemiluminiscence it is important that the handling
procedures of the blood samples have been applied consistently even if the assays
have been performed only a few hours after blood collection.
PMID- 9640103
TI - [Migration and transposition of Oesophagostomum quadrispinulatum larvae from
feces].
AB - Investigations on the migration and translation of free-living stages of
Oesophagostomum quadrispinulatum, using faeces containing eggs as starting
material, revealed that mostly third stage larvae and very few second stage
larvae migrated out of faeces, whereas first stage larvae remained in the faeces.
The emigration rates depended on ambient relative humidity. Compared with the
control, third stage larvae emigrated out of faeces at rates of 0.3%, 1.6% and
12.2% at 50%, 75% and 100% relative humidity, respectively. Offering helminth
free faeces, emigrated third stage larvae returned into faces at rates of 0.4
1.2%, 5.8-17.7%, 39.0-52.7%, and 45.2-60.7% after 1 h, 24 h, 5 days and 14 days,
respectively. After a period of 1, 2, 3 or 4 weeks staying out of faeces,
emigrated third stage larvae returned into faeces at rates of 23.3%, 8.8%, 22.1%
and 6.0%, respectively. An examination of the horizontal translation revealed
that most of the third stage larvae migrated distances up to 80 cm and a few even
up to 150 cm returning into helminth-free faeces.
PMID- 9640104
TI - Studies on biochemical, serological and further characteristics of Streptococcus
porcinus.
AB - In the present study 70 Streptococcus porcinus isolates could be identified and
further characterized by cultural and biochemical properties, by determination of
their antibiotic susceptibility and by serological classifications. The S.
porcinus included serogroup- and serotype-reference strains, presumptive group
candidates and isolates obtained from routine diagnostics. All cultures
investigated appeared with a broad zone of beta-haemolysis on sheep blood agar
showed a CAMP-like reactivity in the zone of staphylococcal beta-lysin and had
the typical biochemical properties of this species. Determination of antibiotic
susceptibility revealed a high number of cultures to be susceptible to
ampicillin, bacitracin, chloramphenicol, penicillin and vancomycin. Resistances
could be observed for erythromycin, minocycline, sulfamethoxazole-trimethoprim,
streptomycin and tetracycline. Serogrouping and serotyping could be performed
with autoclaved extracts of the bacteria and group- and type-specific antisera
prepared against reference strains and group candidates by immunodiffusion
reactions. By serogrouping almost all cultures could be classified into serogroup
E, U, V or P. Some group E streptococci could additionally be serotyped with type
II, VI, VII and group X specific antiserum indicating that group X represents an
additional type antigen of serogroup E. None of the antigen preparations reacted
with serotype IV, V or group candidate NG1 specific antiserum. The described
properties might help to identify and further characterize isolates of the
species. S. porcinus, possibly useful in epidemiological aspects.
PMID- 9640105
TI - Comparative studies of diagnostic bacteriological methods for the recovery of
Salmonella from faecal samples from flocks of layers.
AB - Several conventional culture procedures were compared for the recovery of
Salmonella from faecal samples of layer flocks. The cultural media employed
consisted of Rappaport-Vassiliadis and tetrathionate broth for selective
enrichment and three different plating media (Brilliant Green, Xylose-Lysine
Desoxycholate and modified semisolid Rappaport-Vassiliadis medium). The initial
enrichment and plating procedures were repeated in a four-stage secondary
enrichment. Selective enrichment in Rappaport-Vassiliadis or tetrathionate broth
followed by plating on modified semisolid Rappaport-Vassiliadis medium (selective
motility enrichment) resulted in a significantly higher isolation rate for
Salmonella from faecal samples of layers compared to Brilliant Green and Xylose
Lysine-Desoxycholate medium. The selective enrichment yielded additional
Salmonella isolates up to the second stage. Further enrichment did not increase
the isolation rate.
PMID- 9640106
TI - Report of a case of pyogenic arthritis associated with Actinomyces pyogenes in a
chamois (Rupicapra pyrenaica).
AB - A case of pyogenic arthritis associated to an Actinomyces pyogenes infection in a
chamois (Rupicapra pyrenaica) is described. The animal was a 5-year-old female
that had been seen alone in a wooded area close to a small town in November 1995,
and was lame on one front limb. One month later, it was seen again in a nearby
area. Its lameness had worsened and it knuckled on both front limbs while eating.
Its nutrition status had worsened considerably. On 8 January 1996 the animal was
found dead. It was cachectic, its metatarsal/metacarpal-digital joints were all
swollen and its hoofs were longer than normal. The microbiological study of the
samples obtained showed a large number of beta-haemolytic colonies subsequently
identified as Actinomyces pyogenes. Obligate anaerobic bacteria were not isolated
from the samples.
PMID- 9640107
TI - Raman spectroscopy.
PMID- 9640108
TI - Intravenous anaesthesia: a step forward.
PMID- 9640109
TI - Pharmacokinetic concepts for TCI anaesthesia.
AB - The development of new short-acting anaesthetic drugs, improved drug assay
techniques and the availability of reliable infusion systems opened the field of
clinical pharmacokinetics and pharmacodynamics. The tri-exponential drug
concentration decay complicates the definition of therapeutic dosage regiments
and prevents straightforward prediction of recovery from drug effects. The
context-sensitive half-time, the time required for drug blood concentration to
decrease to half its value, provides a useful comparative predictor of drug
concentration decline after infusion. The effect-site equilibration time
contributes to the delay of drug effect and intensifies the disequilibrium
between drug blood concentrations and obtained effect following incremental
dosage. The rationale for drug infusion is reduction of fluctuating drug
concentrations and drug effects. A variability similar to that observed with the
use of inhalation agents, must be achieved by the choice of an appropriate
pharmacokinetic model. The use of a target controlled infusion device, delivering
proportional changes based on pharmacokinetic principles, allows titration of the
concentration against clinical effect in individual patients.
PMID- 9640110
TI - The development of 'Diprifusor': a TCI system for propofol.
AB - The 'Diprifusor' target controlled infusion system has been developed as a
standardised infusion system for the administration of propofol by target
controlled infusion. A preferred set of pharmacokinetic parameters for propofol
was selected using computer simulation of a known infusion scheme with
pharmacokinetic parameters described in published literature. The selected model
was included in a 'Diprifusor' module that was interfaced with, and later
incorporated into, a computer-compatible infusion pump. Clinical trials with such
systems led to guidance on appropriate target concentrations for the
administration of propofol by 'Diprifusor' target controlled infusion for
inclusion in drug prescribing information. Standardisation of the delivery
performance (+/- 5%) of commercial systems has been achieved with a laboratory
performance specification. Clinical studies indicate that the actual blood
concentrations achieved were about 16% greater than the calculated values
displayed by the system. In an individual patient, titration of the target
concentration is required in the same manner as an anaesthetic vapouriser is
adjusted to obtain a specific pharmacodynamic effect.
PMID- 9640111
TI - Development of the technology for 'Diprifusor' TCI systems.
AB - The availability of fast-acting intravenous drugs for anaesthesia has encouraged
anaesthetists to gain a practical understanding of the pharmacodynamics and
pharmacokinetics of these drugs to optimise their administration. 'Diprifusor'
technology uses pharmacokinetic modelling to control the infusion rate of a pump,
providing the anaesthetist with direct control of the blood concentration rather
than indirect control by the infusion rate. The 'Diprifusor' electronics module
is a dual microprocessor component that can be incorporated into an infusion pump
to provide this mode of administration. This paper describes the module's
infusion control system, prefilled syringe recognition system and the safety
aspects addressed by the design.
PMID- 9640112
TI - Practical use of 'Diprifusor' systems.
AB - This paper describes practical aspects relating to the safe use of target
controlled infusion systems in anaesthesia. Consideration is given to the correct
use of syringes and infusion lines for any target controlled infusion system. The
importance of appropriate connections, minimising infusion line dead space and
the avoidance of syphoning are emphasised. The first two commercially available
infusion pumps to incorporate the 'Diprifusor' module for the administration of
propofol by target controlled infusion are the Graseby 3500 (Graseby Medical Ltd)
and the Vial Master TCI (Fresenius Vial SA, originally developed by Becton
Dickinson). Particular features of these systems are discussed. Finally, the
practical consequences of possible misuse of infusion systems incorporating
pharmacokinetic models are considered.
PMID- 9640113
TI - TCI: supplementation and drug interactions.
AB - The pharmacokinetic and pharmacodynamic interactions between propofol and
adjuvant agents have increasingly been recognised as clinically important and the
improved knowledge of these interactions is being used to optimise the quality of
intravenous anaesthesia. It is now known that propofol interferes with opioid
metabolism, thereby increasing the plasma concentrations of the opioids, while
opioids such as alfentanil increase propofol concentrations by reducing both the
distribution and clearance of propofol. The pharmacokinetic interactions,
however, are of relatively minor clinical importance compared with
pharmacodynamic interactions. The pharmacodynamic interaction between propofol
and other sedative agents, or one of the synthetic opioids, is synergistic. From
the pharmacodynamic interaction data, optimal target propofol-opioid
concentrations and optimal infusion regimens have been developed that ensure
adequate anaesthesia in 50% and 95% of patients with the most rapid recovery
possible. These optimal target propofol concentrations and infusion regimens are
affected by the opioid with which propofol is combined, as well as the duration
of infusion.
PMID- 9640114
TI - Intravenous anaesthesia: manual infusion schemes versus TCI systems.
AB - Propofol was first used to induce and maintain anaesthesia in the early 1980s.
Several infusion regimens were described, some based on pharmacokinetic
predictions. Advances in computing technology subsequently have allowed the
development of portable target controlled infusion devices, with drugs delivered
to achieve specific predicted target blood propofol concentrations. Assessments
of propofol target controlled infusion systems in clinical practice and
comparisons of 'Diprifusor' target controlled infusion systems with manual
infusion are reviewed here.
PMID- 9640115
TI - 'Diprifusor' for general and day-case surgery.
AB - Total intravenous anaesthesia may be most beneficial for day-case surgery with
regard to quality of recovery, lack of complications and the ability to sustain
an efficient throughput of patients. However, the technique can be applied to all
forms of surgery and, with a little practice, consistent results will be
achieved. Computerised infusion pumps can be programmed to provide a target blood
concentration that can be easily varied to alter the anaesthetic state. The
commercially available 'Diprifusor', a target controlled infusion system for
propofol, can facilitate the more widespread use of total intravenous techniques
and allow their potential benefits to be applied and appreciated more widely.
This review outlines some practical considerations that should enable a more
confident approach to total intravenous techniques by anaesthetists who are
unfamiliar with them.
PMID- 9640116
TI - Use of 'Diprifusor' in anaesthesia for ophthalmic surgery.
AB - A technique of balanced anaesthesia involving propofol infusions and a rapidly
metabolised opioid offers advantages over traditional anaesthetic techniques for
eye surgery. The most appropriate mode of delivery of propofol is by a
'Diprifusor' target controlled infusion system. This paper discusses the use of a
'Diprifusor' target controlled infusion system for eye surgery. Published data
are reviewed and the results of a retrospective analysis of 138 successive eye
surgery patients are presented.
PMID- 9640117
TI - 'Diprifusor' for neurosurgical procedures.
AB - The pharmacokinetic profile of propofol is an advantage in neurosurgery, where
the rapid return of cognitive function is essential for an early postoperative
assessment of neurological status. Administration of propofol by 'Diprifusor'
target controlled infusion allows induction of anaesthesia in neurosurgical
patients without significant reduction of mean arterial pressure or occurrence of
apnoeic episodes. This short paper describes our experience of 'Diprifusor'
target controlled infusion for neuroanaesthesia in a series of 20 patients
undergoing craniotomy for excision of epileptic foci. The results have been
compared with ten similar operations where propofol infusion was controlled
manually.
PMID- 9640118
TI - Future applications for TCI systems.
AB - Infusion pumps incorporating 'Diprifusor' for the administration of propofol by
target controlled infusion are now commercially available and are becoming more
widely used. This paper considers possible future applications of target
controlled infusion and summarises results obtained using prototype systems as a
component of other control techniques and with other drugs. These include studies
with patient-controlled systems for the administration of analgesia or sedation
and a closed loop control system for the administration of propofol. Among
currently available analgesic drugs, alfentanil and remifentanil are considered
to be the most suitable for administration by target controlled infusion, but
commercial systems for these agents are not yet available.
PMID- 9640119
TI - Evaluation of the predictive performance of a 'Diprifusor' TCI system.
AB - The predictive performance of a 'Diprifusor' target controlled infusion system
for propofol was examined in 46 patients undergoing major surgery, divided into
three age groups (18-40, 41-55 and 56-80 years). Measured arterial propofol
concentrations were compared with values calculated (predicted) by the target
controlled infusion system. Performance indices (median performance error and
median absolute performance error) were similar in the three age groups, with
study medians of 16.2% and 24.1%, respectively. Mean values for 'divergence' and
'wobble' were -7.6%.h-1 and 21.9%, respectively. Measured concentrations tended
to be higher than calculated concentrations, particularly following induction or
an increase in target concentration. The mean (SD) propofol target concentration
of 3.5 (0.7) micrograms.ml-1 during maintenance was lower in older patients,
compared with higher target concentrations of 4.2 (0.6) and 4.3 (0.7)
micrograms.ml-1 in the two younger age groups, respectively. The control of depth
of anaesthesia was good in all patients and the predictive performance of the
'Diprifusor' target controlled infusion system was considered acceptable for
clinical purposes.
PMID- 9640120
TI - Influence of pre-anaesthetic medication on target propofol concentration using a
'Diprifusor' TCI system during ambulatory surgery.
AB - The effects of pre-anaesthetic medication on target propofol concentration,
induction dose, time to induction, and discomfort on infusion were studied in 45
female patients undergoing ambulatory gynaecological procedures using
'Diprifusor' target controlled infusion of propofol. The patients were randomly
allocated to receive either no premedication (group 1) or premedication with
diazepam alone (group 2) or in combination with alfentanil (group 3). Induction
was more successful in premedicated than unpremedicated patients with an initial
target propofol concentration of 4 micrograms.ml-1 (87% in group 2 and 93% in
group 3 vs. 38% in group 1, p < 0.01). Premedication was also associated with the
requirement of a lower mean target concentration for induction, a lower induction
dose and a shorter time to induction. There were no significant between-group
differences in discomfort on infusion or target concentration during maintenance.
For short ambulatory procedures, the recommended initial target concentration of
propofol is 4 micrograms.ml-1 in premedicated and 6 micrograms.ml-1 in
unpremedicated patients.
PMID- 9640121
TI - Influence of analgesic supplementation on the target propofol concentrations for
anaesthesia with 'Diprifusor' TCI.
AB - Forty healthy patients undergoing orthopaedic surgery were randomly allocated to
receive an initial blood propofol target concentration of either 4 micrograms.ml
1 or 6 micrograms.ml-1 for induction of anaesthesia with a 'Diprifusor' target
controlled infusion system for propofol, and analgesic supplementation with
either nitrous oxide 67% in oxygen or alfentanil 15-20 micrograms.kg-1.h-1.
Anaesthesia was induced within 3 min in 80% and 95% of patients with propofol
target concentrations of 4 micrograms.ml-1 and 6 micrograms.ml-1, respectively.
The frequency of discomfort on infusion was similar for both target
concentrations. During maintenance, supplementary doses of alfentanil were
required to provide adequate surgical conditions in approximately half of the
patients receiving nitrous oxide. There was no statistically significant
difference between the target concentration [mean (SD)] of propofol for total
intravenous anaesthesia [5.1 (2.0) micrograms.ml-1] compared with a technique
using nitrous oxide [4.6 (1.2) micrograms.ml-1] supplemented as needed with small
doses of alfentanil.
PMID- 9640122
TI - Influence of ventilatory mode on target concentrations required for anaesthesia
using a 'Diprifusor' TCI system.
AB - This study examined the influence of mode of ventilation (spontaneous or
controlled) on the target blood concentrations required to maintain anaesthesia
with 'Diprifusor' (a target controlled infusion system for propofol) in 40
healthy, unpremedicated, adult patients undergoing knee arthroscopy. All patients
were given alfentanil (10 micrograms.kg-1) and ketorolac (10 mg) immediately
before induction and all received a 2:1 mixture of nitrous oxide:oxygen. An
initial target blood concentration of propofol of 6.0 micrograms.ml-1 was used in
most patients to induce anaesthesia. The blood target concentration required to
produce acceptable anaesthetic conditions was not significantly influenced by the
mode of ventilation. The mean maintenance target concentration for propofol was
3.9 (SD 0.83) micrograms.ml-1 in the ventilated group and 3.5 (SD 0.82)
micrograms.ml-1 in the group of patients breathing spontaneously.
PMID- 9640123
TI - TCI compared with manually controlled infusion of propofol: a multicentre study.
AB - This prospective, randomised multicentre study was designed to determine the
clinical profile of 'Diprifusor' target controlled infusion compared with
manually controlled infusion of propofol in 562 patients, aged 18-85 years, in a
range of surgical procedures in 29 centres. The dose of propofol required for
loss of consciousness was statistically significantly lower in the target
controlled infusion group [1.69 (0.50) vs. 2.31 (0.75) mg.kg-1, p < 0.001] but
the overall rate of propofol administration was slightly, but significantly,
higher [12.1 (5.1) vs. 11.0 (6.0) mg.kg-1.h-1, p < 0.05]. The target
concentration (CT) required for induction decreased with increasing age and ASA
class, with premedication and with the administration of an opioid before
induction. However, the amount of opioid given did not influence the CT required
for induction, but enhanced the haemodynamic effects of propofol induction in
both groups. Most investigators expressed an overall preference for target
controlled infusion (93%) and found it easier to use (76%). Despite the lack of
experience of most investigators in using target controlled infusion, the
clinical profiles of both propofol administrations were similar. Data suggest
that the clinical profile of target controlled infusion may be improved with
experience, for example by more active titration of CT to effect. Target
controlled infusion may well become the preferred choice for anaesthetists.
PMID- 9640124
TI - Gene therapy in autoimmune diseases.
PMID- 9640125
TI - Can non-fundable trials be conducted anyway? The case for open, randomised,
actively controlled trials in rheumatology.
PMID- 9640126
TI - Unexplained hip pain: look beyond the obvious abnormality.
PMID- 9640127
TI - Do the radiological changes of classic ankylosing spondylitis differ from the
changes found in the spondylitis associated with inflammatory bowel disease,
psoriasis, and reactive arthritis?
AB - OBJECTIVE: In 1971 McEwen and colleagues suggested that the radiological changes
of classic ankylosing spondylitis (AS), and the changes of the spondylitis
associated with inflammatory bowel disease differ in several respects from the
radiological features of psoriatic and reactive spondylitis. The findings of this
study have never been confirmed. The aim of this study was to replicate the
McEwen study comparing films blinded to diagnostic group. METHODS: The study
population comprised 91 patients with classic AS, 15 patients with regional
enteritis, 16 patients with ulcerative colitis, five patients with sexually
acquired reactive arthritis, two with post-dysenteric arthritis, and 34 with
psoriatic arthritis. Blinded reading of spinal radiographs was undertaken,
scoring for severity, symmetry, paravertebral ossification, size of
syndesmophytes, ligamentous calcification, squaring, discitis, pseudofractures,
zygoapophyseal joint involvement, and complete ankylosis. RESULTS: Comparison of
the four groups--classic, enteropathic, psoriatic, and reactive AS--showed
differences with respect to symmetry of sacroiliitis, symmetry of lumbar spinal
involvement, and frequency and size of syndesmophytes. Zygoapophyseal joint
involvement was more frequent in the lumbar spine in classic and enteropathic
spondylitis but no between group differences were found with respect to
symphisitis, squaring, apophyseal joint involvement and ligamentous calcification
in the lumbar spine, and other areas. CONCLUSIONS: Some of the radiological
differences described by McEwen et al, notably the asymmetry, the less severe
changes, and the distinctive syndesmophytes in psoriasis, have been confirmed. A
number of phypotheses are proposed to explain these differences including
biomechanical, biochemical, and genetic factors.
PMID- 9640128
TI - Clinical spectrum associated with positive ANCA titres in 94 consecutive
patients: is there a relation with PR-3 negative c-ANCA and
hypergammaglobulinaemia?
AB - OBJECTIVE: To calculate the positive predictive value (ppv) of cytoplasmic
antineutrophil cytoplasmic antibodies (c-ANCAs) and anti-proteinase 3 (PR 3)
antibodies for Wegener's granulomatosis (WG) and to evaluate their association
with other diseases. METHODS: The clinical files of all 94 patients who had a
positive c- or perinuclear (p)-ANCA test, or both, in the laboratory of the
University Hospital, Leuven between April 1995 and March 1996 and who attended
the Internal Medicine Department of the hospital were retrospectively studied.
RESULTS: Of the 94 patients with ANCAs (fluorescence titre > or = 1/40), 57 were
c-ANCA positive and 45 p-ANCA positive (eight were simultaneously c- and p-ANCA
positive). Of the 57 c-ANCA positive patients, 23 had WG. The ppv for WG thus was
40%. This value did not increase by defining a higher threshold for a positive
ANCA. There was not a good relation between ANCA titres and disease activity in
the WG patients, nor was there a relation between anti-PR 3 antibody levels and
WG disease activity. The ppv of anti-PR 3 antibodies for WG however was very high
(85%). There was a positive correlation between the level of (hyper)
gammaglobulinaemia and c-ANCA titres in those patients with final diagnoses not
known to be associated with c-ANCA. Forty five patients had positive p-ANCAs. The
largest group were those with inflammatory bowel disease (n = 20, of whom the
majority had colitis ulcerosa or primary sclerosing cholangitis, or both); the
great majority of these patients had no anti-myeloperoxidase antibodies.
Vasculitis was present in eight patients, of whom two had WG (both were also c
ANCA positive). CONCLUSION: There is a low ppv of c-ANCAs for WG, caused by a
high percentage of PR 3 negative, positive c-ANCA determinations, possibly
related to hypergammaglobulinaemia. Anti-PR 3 antibodies have a high ppv for WG.
However, neither c-ANCA titre, nor the level of anti-PR 3 antibodies correlated
with the activity of the disease.
PMID- 9640129
TI - Effects of patient education on compliance with basic treatment regimens and
health in recent onset active rheumatoid arthritis.
AB - OBJECTIVES: To determine the effects of patient education on compliance and on
health in patients with active, recent onset rheumatoid arthritis (RA). METHODS:
A randomised, controlled, assessor blinded, one year trial. The experimental
group followed an education programme. All patients started on sulphasalazine
therapy. Compliance with sulphasalazine was measured by pill counting. Compliance
rates with regimens of physical exercise, endurance activities, and energy
conservation were measured by questionnaires. Compliance with prescriptions of
joint protection was scored using a test for joint protection performance. Health
was measured by a Disease Activity Score (function of erythrocyte sedimentation
rate, Ritchie score, and number of swollen joints), C reactive protein, Dutch
AIMS scores, and M-HAQ scores, range of motion of shoulder, elbow, and knee
joints. Parameters were scored at baseline and after three, six, and 12 months.
RESULTS: Sixty of 65 patients gave informed consent, five of them withdrew from
follow up. Compliance with sulphasalazine exceeded 80% with no differences
between groups. Compliance with physical exercise (at three months), energy
conservation (at three and at 12 months), and joint protection (at three months)
improved significantly more in the experimental group. The improvements of health
were not different in the groups. CONCLUSION: Compliance with sulphasalazine
among patients with active, recent onset RA is high, whether formal patient
education is followed or not. Compliance with physical exercise, energy
conservation, and joint protection was increased by patient education. Formal
patient education did not improve health status.
PMID- 9640130
TI - Quantitative assessment of the rheumatoid synovial microvascular bed by
gadolinium-DTPA enhanced magnetic resonance imaging.
AB - OBJECTIVE: To examine the relation between rate of synovial membrane enhancement,
intra-articular pressure (IAP), and histologically determined synovial
vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic
resonance imaging (MRI). METHODS: Dynamic gadolinium-DTPA enhanced MRI was
performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients
vascular morphometry study). Rate of synovial membrane enhancement was quantified
by line profile analysis using the image processing package ANALYZE. IAP was
measured using an intra-compartmental pressure monitor system. Multiple synovial
biopsy specimens were obtained by a blind biopsy technique. Blood vessels were
identified immunohistochemically using the endothelial cell marker QBend30 and
quantified (blood vessel numerical density and fractional area). RESULTS: Median
blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3
110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane
enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with
both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel
fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of
enhancement. CONCLUSIONS: Gadolinium-DTPA enhanced MRI may prove to be a valuable
technique for evaluating drugs that influence angiogenesis.
PMID- 9640131
TI - Rheumatoid synovial endothelial cells secrete decreased levels of tissue
inhibitor of MMP (TIMP1).
AB - OBJECTIVES: Angiogenesis (the formation of new blood vessels) is a major
component of the inflammatory pannus in rheumatoid arthritis (RA). Matrix
metalloproteinase (MMP) secretion by microvascular endothelial cells is an
essential step in angiogenesis. The secretion of MMP1, MMP2, MMP9, and TIMP1 by
human microvascular endothelial cells derived from RA synovium (RASE) to normal
synovium (NSE) and neonatal foreskin (FSE) was compared. METHODS: Confluent
monolayers of endothelial cells in basal medium were pre-incubated for 24 hours
in the presence or absence of phorbol myristate acetate (PMA, 100 ng/ml). MMP1
activity was measured using a spectrophotometric assay and western blotting. MMP2
and MMP9 were measured using zymography. TIMP1 was measured by enzyme linked
immunosorbent assay and western blotting. RESULTS: There was little difference
between the amounts of MMP2 secreted by any of the cell lines. In response to PMA
both synovial cell types showed a significantly higher MMP1 and MMP9 activity
compared with FSE, although there was no difference between RASE and NSE. Tumour
necrosis factor alpha had minimal effect on MMP activity. There was a striking
decrease in the amount of TIMP1 secreted by RASE compared with normal synovium.
CONCLUSIONS: As overall MMP activity is a balance between the amount of MMP and
TIMP1 present, the low levels of TIMP1 produced by RASE would shift the balance
in favour of increased MMP activity by these cells. This is likely to contribute
to the angiogenic potential of RASE.
PMID- 9640132
TI - Inactivation of antithrombin III in synovial fluid from patients with rheumatoid
arthritis.
AB - OBJECTIVE: To investigate the thrombin inhibitory capacity of antithrombin III in
the inflamed human joint. METHODS: Thrombin inhibitory capacity was measured,
using a kinetic spectophotometric method, in matched plasma and synovial fluid
samples of patients with rheumatoid arthritis (n = 22) and osteoarthritis (n =
16), together with normal control plasma samples (n = 13). In the same samples,
the concentration of antithrombin III was also determined by the method of radial
immunodiffusion. The combination of these measurements allowed the calculation of
the specific thrombin inhibitory capacity of these samples. RESULTS: An increased
concentration of antithrombin III in rheumatoid compared with osteoarthritic
synovial fluid was noted (p < 0.05). However, there was a significant depression
in the specific activity of antithrombin III in rheumatoid synovial fluid when
compared with matched plasma samples (p < 0.001) or with osteoarthritic synovial
fluid (p < 0.05). CONCLUSION: In rheumatoid synovial fluid the thrombin
inhibitory capacity of antithrombin III is disproportionately depressed relative
to the concentration of antithrombin III, indicating the inactivation of
antithrombin III in the rheumatoid joint.
PMID- 9640133
TI - The occurrence of falls among patients with a new episode of hip pain.
AB - OBJECTIVES: To establish the risk of falling among those who consult their
general practitioner with a new episode of hip pain and to discover if risk is
altered by age and according to whether, at presentation, signs of osteoarthritis
are present on radiography. METHODS: A case-control study was conducted. Cases
were all patients who presented with a new episode of hip pain to participating
general practices throughout the United Kingdom. All cases had a pelvic
radiograph taken on recruitment to the study. Three controls were matched for
sex, age, and general practice to each case. A questionnaire was sent by post to
all cases and controls. The risk of having fallen in the past 12 months among
cases and controls was compared. RESULTS: The study included 111 cases presenting
with hip pain and 229 controls who had not consulted with hip pain in the
previous 12 months. Women (odds ratio = 3.6, 95% CI 1.9, 6.7) but not men (odds
ratio = 0.8, 95% CI 0.3, 2.3) reported an increased risk of falling in the
previous 12 months. Similar results were obtained when the previous four months
were considered. For all cases, hip pain predated any reported falls. The
increased risk in women was found particularly for those aged less than 70. Risk
of falling was not altered by the presence of radiological changes of
osteoarthritis. CONCLUSIONS: Hip pain, which may be a symptom of osteoarthritis
of the hip, increases the risk of falling. This finding has implications for the
advice offered by general practitioners to patients who consult with early hip
pain.
PMID- 9640134
TI - Multiple extra-articular synovial cyst formation: case report and review of the
literature.
AB - OBJECTIVE: To investigate the clinical manifestations and the treatment strategy
of a very rare entity of disease manifesting as multiple extra-articular cystic
synovitis with recurrent polyarthralgia. METHODS: A 47 year old male patient with
multiple extra-articular synovial cysts was followed up prospectively for 13
years. The clinical manifestations and response to various treatments were
recorded. Comparisons are made among the five reported cases (including the
present case). RESULTS: Multiple synovial cysts over the tendon sheath and bursae
appeared successively with and without antecedent growth of nodules during 13
years of follow up. Although polyarthralgia and high titred rheumatoid factor
persisted throughout the course, there were no roentgenographical changes of
joints specific to rheumatoid arthritis (RA). The synovial cysts and arthralgia
failed to respond to any of the disease modifying anti-rheumatic drugs (DMARDs)
prescribed. Systemic involvements such as pulmonary interstitial fibrosis and
skin ulcers were also noted, but they were not progressive. CONCLUSIONS: Multiple
extra-articular cystic synovitis is an uncommon disease entity closely related to
RA. It has been reported exclusively in Japanese subjects and therefore some
cultural factors, either genetic or environmental, may contribute to its
development.
PMID- 9640135
TI - Fatal vascular occlusion in juvenile dermatomyositis.
PMID- 9640136
TI - Polyarteritis nodosa associated with precore mutant hepatitis B virus infection.
PMID- 9640137
TI - Polymyalgic presentation of Sjogren's syndrome: a report of three patients.
PMID- 9640138
TI - Duration of methotrexate treatment until partial and total remission of
refractory juvenile rheumatoid arthritis.
PMID- 9640139
TI - Lipid profiles in patients with rheumatoid arthritis.
PMID- 9640140
TI - Smoking, rheumatoid factors, and rheumatoid arthritis.
PMID- 9640141
TI - Pain after amputation: is prevention better than cure?
PMID- 9640142
TI - Onset times and intubating conditions.
PMID- 9640143
TI - Does ketorolac cause postoperative renal failure: how do we assess the evidence?
PMID- 9640144
TI - Ventilatory assistance and respiratory muscle activity. 1: Interaction in healthy
volunteers.
AB - We have investigated the response of 12 normal, healthy subjects to resistance
loading and ventilator assistance of spontaneous breathing. Three ventilators,
the Hamilton Veolar, Engstrom Erica and Puritan Bennett 7200, were used to
provide synchronized intermittent mandatory ventilation and two levels of
pressure assistance. Total respiratory elastance and resistance were measured.
The equivalent (negative) pressure of respiratory muscle activity (pmus) was then
calculated from measurement of flow and pressure at the mouth. With ventilatory
assistance, subjects maintained frequency, decreased inspiratory time and the
magnitude of pmus, but increased tidal volume, thus not taking full advantage of
ventilatory assistance. The waveform of pmus varied in detail within and between
subjects and conditions, but the all-subject mean waveforms showed for all
conditions a consistency of trajectory. Increasing the level of assistance
decreased the duration and hence the (negative) peak value of pmus. The results
suggest that some waveforms of flow or pressure from the ventilators may be more
acceptable to patients than others, and that different patients may prefer
different waveforms.
PMID- 9640145
TI - Ventilatory assistance and respiratory muscle activity. 2: Simulation with an
adaptive active ("aa" or "a-squared") model lung.
AB - The aim of this study was to develop a lung model which adapted its active
simulation of spontaneous breathing to the ventilatory assistance it received--an
"aa" or "a-squared" lung model. The active element required was the waveform of
negative pressure (pmus), which is equivalent to respiratory muscle activity.
This had been determined previously in 12 healthy volunteers and comprised a
contraction phase, relaxation phase and expiratory pause. Ventilatory assistance
had shortened the contraction and relaxation phases without changing their shape,
and lengthened the pause phase to compensate. In this study, the contraction and
relaxation phases could be adequately represented by two quadratic equations, in
addition to a third to provide a smooth transition. Therefore, the adaptive
element required was the prediction of the duration of the contraction phase. The
best predictive variables were flow at the end of contraction or peak mouth
pressure. Determination of either of these allowed adjustment of the "standard"
waveform to the level of assistance produced by an "average" ventilator, in a
manner that matched the mean response of 12 healthy conscious subjects.
PMID- 9640146
TI - Effect of different doses of inhaled nitric oxide on pulmonary capillary pressure
and on longitudinal distribution of pulmonary vascular resistance in ARDS.
AB - Inhaled nitric oxide lowers pulmonary capillary pressure (PCP) in animals and in
patients with acute respiratory distress syndrome (ARDS). A dose-response
relationship in patients with ARDS has not yet been established. Therefore, we
studied the effects of four concentrations of nitric oxide (1, 10, 20 and 40
volumes per million (vpm)) in random order, on PCP in 19 patients with ARDS. PCP
was estimated by visual analysis of the pressure decay curve after balloon
inflation of the pulmonary artery catheter. Haemodynamic and gas exchange
variables were measured at each nitric oxide concentration. Patients were
classified as responders when PCP decreased by at least 2 mm Hg after nitric
oxide 20 vpm. In responders (n = 8), nitric oxide decreased PCP and post
capillary vascular resistance dose-dependently and changed longitudinal
distribution of pulmonary vascular resistance with a maximum effect at 20 vpm. In
non-responders (n = 11), PCP did not change. In both groups, the nitric oxide
induced decrease in pre-capillary vascular resistance was small with a maximum
effect at 1 vpm. In ARDS, vasodilatation of pre-capillary vessels is achieved at
low concentrations of nitric oxide, whereas the effect of nitric oxide on
postcapillary vessels is variable. Higher concentrations may be required for
optimal post-capillary vasodilatation in a subgroup of ARDS patients.
PMID- 9640147
TI - Influence of surgical technique on early postoperative hypoxaemia in children
undergoing elective palatoplasty.
AB - We have assessed the influence of different surgical procedures on the incidence,
severity and duration of early postoperative hypoxaemia in 312 healthy infants
and children undergoing elective palatoplasty. Group 1 patients underwent von
Langenbeck palatoplasty (n = 149), group 2 patients underwent push-back
palatoplasty (n = 124) and group 3 patients underwent combined push-back
palatoplasty and superior pharyngeal flap surgery (n = 39). Arterial oxygen
saturation (SpO2) was recorded while patients were breathing air shortly after
arrival in the recovery room (0 min), and at 5, 10, 15, 20, 30, 40, 50, 60, 120
and 180 min thereafter. Patients who underwent more complex surgical techniques
for palatoplasty had lower postoperative SpO2 values, slower recovery of SpO2 and
a higher incidence of hypoxaemia during the early postoperative period. There
were significant differences in postoperative SpO2, values and the incidence of
hypoxaemia. The incidences of hypoxaemia and severe hypoxaemia were 27% and 1%,
respectively, in group 1, 37% and 12% in group 2, and 36% and 33% in group 3.
Hypoxaemia occurred most commonly in the first 15 min in children after von
Langenbeck palatoplasty, in the first 40 min after push-back palatoplasty and in
the 120 min after combined push-back palatoplasty and superior pharyngeal flap
surgery. There were significant associations between low SpO2 values, incidence
of hypoxaemia on admission to the recovery room and recovery scores.
PMID- 9640148
TI - Sevoflurane compared with halothane for tracheal intubation in children.
AB - We have studied 40 healthy children, aged 3-10 yr, undergoing adenotonsillectomy,
in a double-blind, randomized study. Intubating conditions were assessed when the
pupils had become small and central after inhalation induction with either 5%
halothane and 60% nitrous oxide in oxygen or 8% sevoflurane and 60% nitrous oxide
in oxygen. The quality of tracheal intubation was graded according to ease of
laryngoscopy, position of the vocal cords, coughing, jaw relaxation and movement
of limbs. Fewer children had significant vocal cord movement on laryngoscopy (P <
0.01) and more had ideal intubating conditions when halothane was used (12 of 20
compared with seven of 20; ns). Time to reach the clinical end-point for
intubation was reached sooner with halothane (P = 0.015). In all children the
trachea was intubated successfully at the first attempt and all remained
haemodynamically stable throughout induction.
PMID- 9640149
TI - Induction and emergence in infants less than 60 weeks post-conceptual age:
comparison of thiopental, halothane, sevoflurane and desflurane.
AB - We have studied 40 infants with a post-conceptual age of less than 60 weeks
undergoing general anaesthesia for herniotomy. Patients were anaesthetized with 1
MAC equivalent values for age and agent and allocated randomly to receive
halothane, savoflurane or thiopental for induction, and halothane, sevoflurane or
desflurane for maintenance of anaesthesia. At induction, both time to acceptance
of a face mask and loss of eyelash reflex were recorded. Emergence times were
noted by a blinded observer. Induction and emergence times were similar between
the halothane and sevoflurane groups but were consistently shorter in the
desflurane group compared with the halothane or sevoflurane groups. There were no
problems at extubation or significant apnoea in any group. Induction of
anaesthesia in this population was no quicker with sevoflurane than with
halothane and the method used for induction did not influence recovery time.
Maintenance of anaesthesia with desflurane resulted in a shorter recovery time in
infants in whom anaesthesia was induced with halothane or thiopental. Desflurane
maintenance may be particularly beneficial in the neonate.
PMID- 9640150
TI - Surgical/tourniquet pain accelerates blood coagulability but not fibrinolysis.
AB - Tissue damage during surgery induces coagulation factors and activates platelets.
Surgical pain may provoke release of catecholamines, leading to
hypercoagulability. We have investigated the effect of surgical pain on blood
coagulability and fibrinolysis in orthopaedic operations using tourniquets in 22
patients undergoing total knee replacement. Patients were allocated to one of two
groups to receive extradural anaesthesia (EA; n = 11) or general anaesthesia (GA;
n = 11). The EA group received lumbar extradural block with lidocaine. The GA
group received only general anaesthesia, maintained with 1.5-2.5% sevoflurane and
66% nitrous oxide in oxygen. Using a thrombelastogram technique, blood
coagulability and fibrinolysis were measured. Mean maximum amplitude (MA), which
reflects coagulability, increased after tourniquet inflation (11%) in group GA
whereas MA in group EA did not change. After tourniquet deflation, MA values in
both GA and EA groups increased significantly (10% and 20%, respectively) (P <
0.05), and there was also a significant difference in MA between groups (P <
0.05). The fibrinolytic rate did not change in either group during tourniquet
inflation, but increased significantly (160%) after tourniquet deflation. There
was no significant difference in fibrinolytic rate between the groups. We
conclude that the hypercoagulability seen in group GA could have been caused by
surgical or tourniquet pain, or both, and that extradural anaesthesia is a useful
technique to prevent hypercoagulability.
PMID- 9640151
TI - Changes in specific markers of haemostasis during reduction mammoplasty.
AB - We have investigated the time course of the coagulation and fibrinolytic changes
during moderate surgical trauma (elective reduction mammoplasty) in the absence
of other confounding factors that could affect haemostasis. Specific markers for
coagulation (prothrombin fragment 1.2 (F1.2), thrombin-antithrombin III complex
(TAT)) and fibrinolysis (plasmin-antiplasmin complex (PAP) and D-dimer) were
examined. Blood samples were obtained in 20 ASA I anaesthetized female patients
at T0 (before operation), T75 (during operation) and T150 (before the end of
operation). There was a progressive increase in blood loss during operation:mean
110 (SD 80) ml at T75 and 470 (180) ml at T150. This was associated with a
significant increase in plasma concentrations of F1.2, PAP and D-dimer at T150
only (P < 0.05 vs T0). We conclude that moderate surgical trauma with blood
losses greater than 300 ml can activate thrombin generation and fibrinolysis
during operation.
PMID- 9640152
TI - Effect of remifentanil on the haemodynamic response to orotracheal intubation.
AB - We have examined the effect of remifentanil on the haemodynamic response to
orotracheal intubation in a randomized, double-blind study. We studied 40
patients allocated to one of four groups of 10 each, to receive the following
immediately before induction of anaesthesia: remifentanil 1 microgram kg-1 bolus
over 30 s, followed by an infusion of 0.5 microgram kg-1 min-1; saline placebo
only; glycopyrrolate 200 micrograms and remifentanil 1 microgram kg-1 bolus over
30 s, followed by an infusion of 0.5 microgram kg-1 min-1; or glycopyrrolate 200
micrograms only. Anaesthesia was induced with propofol, vecuronium and 1%
isoflurane with 66% nitrous oxide in oxygen. The trachea was intubated under
direct laryngoscopy 3 min after induction of anaesthesia. Arterial pressure and
heart rate were measured non-invasively, immediately before induction of
anaesthesia and then at 1-min intervals. Remifentanil was found to effectively
attenuate the pressor response to intubation (P < 0.05 for the increase in mean
arterial pressure; P < 0.01 for the increase in heart rate). In the absence of a
concurrent vagolytic agent, remifentanil was associated with bradycardia or
hypotension, or both, in five of 10 patients, compared with one patient who
received remifentanil and glycopyrrolate.
PMID- 9640153
TI - Appropriate size and inflation of the laryngeal mask airway.
AB - We have compared size 3 and size 4 laryngeal masks in 30 females and size 4 and
size 5 in 30 males for success rate of insertion, incidence of airleak and
pressure exerted on the pharynx. First, the ex vivo volume-pressure relationship
of the mask was obtained. Second, after insertion of a mask, the cuff was
inflated with the recommended maximum volume of air and intracuff pressure
measured. Third, the incidence of airleak during a steady airway pressure of 18
cm H2O was noted. Fourth, the cuff was deflated until it just prevented airleak,
and cuff pressure was measured. The mask was removed, the other size was inserted
and the same procedure repeated. At the end of operation, final in vivo and ex
vivo pressures were measured. The pressure exerted on the pharynx was calculated
as the difference between ex vivo and in vivo intracuff pressures. It was always
possible to insert both sizes in both sexes. In females, airleak occurred in 15
patients with the size 3 and in five patients with the size 4 (difference: P =
0.005) and in males, 21 patients with the size 4 and in four patients with the
size 5 (P < 0.001). Removal of air to the minimum effective volume significantly
decreased intracuff pressure and pressure on the pharynx; on removal of the mask,
pressures were similar to, or lower than, initial pressures. Therefore, a larger
mask (size 4 in females and size 5 in males) provided a better seal than a
smaller size without producing higher pressures on the pharynx.
PMID- 9640154
TI - Changes in mucociliary activity may be used to investigate the airway-irritating
potency of volatile anaesthetics.
AB - We have examined the short-term effects of three volatile anaesthetics,
halothane, isoflurane and desflurane, on mucociliary activity in the rabbit
maxillary sinus in vivo. Mucociliary activity was recorded photoelectrically and
the signal processed by fast Fourier transformation. Administration of 1.0 MAC of
halothane, isoflurane or desflurane caused a temporary increase in mucociliary
activity, with mean peak responses of 47.8 (SEM 13.0)%, 44.0 (9.6)% and 45.1
(23.7)% (n = 6), respectively. The response to all three compounds was biphasic;
an initial peak was observed within 2 min and a second peak at 3-8 min. The
second response was not significant for halothane. In contrast, desflurane
produced a significant second peak while the first was small and failed to reach
significance. Halothane displayed an initial peak within 2 min which was blocked
by atropine but not by the neurokinin 1 (NK1) receptor antagonist CP-99. The
second peak at 3-5 min was less pronounced for halothane than for isoflurane or
desflurane. The second peak was not affected by atropine pretreatment, but was
blocked by pretreatment with CP-99. A combination of atropine and CP-99
pretreatment abolished the mucociliary response to halothane. Atropine
pretreatment did not affect, whereas CP-99 significantly reduced, the response to
desflurane. We conclude that the NK1-mediated response was most pronounced for
desflurane which is considered the most airway irritating compound of the three.
It is likely that the size of the NK1-mediated response reflects the airway
irritating properties of the volatile anaesthetic used.
PMID- 9640155
TI - Cardiovascular effects of concomitant administration of isoflurane and nicorandil
in dogs.
AB - Nicorandil, a new KATP channel opener, is used in clinical practice for anti
anginal therapy. It exhibits vasodilator properties as does the halogenated
anaesthetic isoflurane. We have examined the cardiovascular effects of increasing
concentrations of isoflurane after administration of nicorandil in 10 adult
beagle dogs anaesthetized with thiopental and whose lungs were ventilated
mechanically. During surgery, anaesthesia was maintained with 1.0-1.5%
isoflurane. A left thoracotomy was performed and the heart suspended in a
pericardial cradle. Monitoring included: ECG; aortic, left ventricular, arterial,
central venous and pulmonary artery pressures; cardiac output; coronary flow; and
segmental length in the apical region. After surgery, isoflurane anaesthesia was
set at an end-tidal concentration of 1.05% (1 MAC) and measurements obtained;
these were repeated with 1.4%, 1.75%, 2.1% and 1.05% isoflurane concentrations
after appropriate stabilization periods. Nicorandil (100 micrograms kg-1 bolus,
25 micrograms kg-1 min-1 infusion) was begun and a second dose-response study of
isoflurane was obtained as before. Blood samples were obtained for measurement of
concentrations of nicorandil. Systolic ventricular function was assessed by
systolic shortening (%SS) and preload recruitable stroke work (PRSW). Increasing
isoflurane concentration produced decreases in heart rate, systolic pressure,
cardiac output, %SS and PRSW. Nicorandil produced a slight decrease in systolic
arterial pressure (10 and 15 mm Hg after 1.05% and 2.05% isoflurane) and a slight
increase in heart rate (10 and 5 beat min-1 after 1.05% and 2.05% isoflurane).
Preload, assessed by end-diastolic length, decreased. Coronary blood flow
increased with infusion of nicorandil. Left ventricular function was not affected
by infusion of nicorandil. We conclude that nicorandil has only minor
vaso/venodilatory effects in the presence of isoflurane. Ventricular function was
not altered by infusion of nicorandil.
PMID- 9640156
TI - Population based pharmacokinetic analysis: why do we need it; what is it; and
what has it told us about anaesthetics?
PMID- 9640157
TI - Leucocyte distribution during sevoflurane anaesthesia.
AB - We have examined if sevoflurane anaesthesia per se modified the number of
circulating leucocytes in humans. Fifty-nine patients undergoing elective surgery
were anaesthetized with sevoflurane in oxygen. The inhaled concentration was
increased gradually to 5% and maintained for 20 min. Arterial blood samples were
obtained before induction of anaesthesia and at 20 min. While the total number of
leucocytes remained constant, circulating neutrophils decreased (mean 3370 (SD
1030) mm-3 to 3170 (940) mm-3; P < 0.01) and lymphocytes increased (1870 (520) mm
3 to 2040 (580) mm-3; P < 0.01). We conclude that high concentrations of
sevoflurane modified the distribution of leucocytes in anaesthetized patients.
PMID- 9640159
TI - Caudal anaesthesia with 0.375% ropivacaine or 0.375% bupivacaine in paediatric
patients.
AB - We have determined the effectiveness and degree of motor block produced by the
new local anaesthetic, ropivacaine, when used for caudal anaesthesia in children.
We studied 60 children, aged 3-6 yr, ASA I, allocated randomly in a double-blind
manner, to receive one of two local anaesthetics: 0.375% ropivacaine 1.0 ml kg-1
or 0.375% bupivacaine 1.0 ml kg-1. Patients were anaesthetized with continuous
infusion of propofol 200 micrograms kg-1 min-1. The lungs were ventilated with
50% nitrous oxide in oxygen. Heart rate and arterial pressure were measured every
5 min after administration of local anaesthetic until discharge from the recovery
room. The extent of motor block in the recovery room was scored as 1-3. Adverse
events and time to first analgesic requirements were recorded. Patients in the
two groups did not differ in age, weight or height. There were no differences in
heart rate or arterial pressure between the two groups. No adverse events were
observed. The degree of motor block was significantly different between the two
groups. The ropivacaine group showed a shorter duration of motor block than the
bupivacaine group (P < 0.05). Postoperative analgesia was required at a mean time
of 5 (SD 3.2) h in the ropivacaine group compared with 5 (2.8) h in the
bupivacaine group. These findings suggest that caudal anaesthesia with
ropivacaine in paediatric patients is effective and produces less motor block in
the postoperative period.
PMID- 9640158
TI - Thiopental or etomidate for rapid sequence induction with rocuronium.
AB - We have assessed the effect of the choice of i.v. induction agent on intubation
conditions, 60 s after administration of rocuronium 0.6 mg kg-1. We studied 60
adult patients, allocated randomly to one of two groups. Anaesthesia was induced
with alfentanil 10 micrograms kg-1 followed by thiopental 5 mg kg-1 (AT-R group;
n = 30) or etomidate 0.3 mg kg-1 (AE-R group; n = 30). Both groups received
rocuronium 0.6 mg kg-1. Laryngoscopy was started 60 s later and intubation
conditions were evaluated according to a standard score, which considered ease of
laryngoscopy, condition of the vocal cords and reaction to intubation. In the AT
R group, overall intubation conditions were scored as excellent in 20 patients,
good in nine and fair in the remaining patient. In the AE-R group, overall
intubating conditions were excellent in 24 and good in six patients. The
difference between the two groups was not significant. Of the three components of
the intubation score assessed, response to intubation stimulus was significantly
less pronounced in group AE-R compared with group AT-R (P < 0.05): group AE-R, no
reaction in 24 patients, slight diaphragmatic movement in five and mild coughing
in one patient; group AT-R, no reaction in 13, slight diaphragmatic movement in
14, mild coughing in two and severe coughing in one patient. We conclude that
etomidate as part of an induction regimen containing alfentanil and rocuronium
attenuated the reaction to intubation to a greater extent than thiopental.
PMID- 9640160
TI - Remifentanil in combination with propofol for spontaneous ventilation
anaesthesia.
AB - We have investigated the effect of four doses of remifentanil on the incidence of
respiratory depression and somatic response at incision. Remifentanil was
administered as a loading dose of 0.125, 0.25, 0.375 or 0.5 microgram kg-1 and at
a maintenance infusion rate of 0.025, 0.05, 0.075 or 0.1 microgram kg-1 min-1,
respectively, with an infusion of propofol 6 mg kg-1 h-1. Responses occurred in
88% of patients with remifentanil 0.025 microgram kg-1 min-1 compared with 30-40%
in the other groups. Respiratory depression after incision increased from 6% with
remifentanil 0.025 microgram kg-1 min-1 to 73% with 0.1 microgram kg-1 min-1.
Increases in propofol infusion rate to 7.2-8.4 mg kg-1 h-1 produced adequate
maintenance of anaesthesia. Reductions in remifentanil doses to 0.025-0.05
microgram kg-1 min-1 resulted in adequate respiration at the end of surgery in
88% of patients. Maintenance infusions of the two drugs for spontaneous
ventilation are likely to be in these ranges. However, the ideal loading doses
and infusion rates for induction remain to be established.
PMID- 9640161
TI - Extradural anaesthesia for caesarean section in a patient with syringomyelia and
Chiari type I anomaly.
AB - We describe elective Caesarean section performed under extradural anaesthesia in
a parturient with symptomatic syringomyelia and coexisting Chiari type I anomaly.
Syringomyelia is reviewed and the anaesthetic implications of the condition
discussed. Anaesthesia should be directed primarily at avoidance of increased
intracranial pressure, which can cause sudden deterioration in these patients.
PMID- 9640162
TI - Anaesthetic management in patients suspected of, or at risk of, having
Creutzfeldt-Jakob disease.
AB - We report two young patients who had repeated neurosurgical procedures and who
were thought to be at risk of developing Creutzfeldt-Jakob disease (CJD). The
first patient had been given a lyophilized dural graft in the course of removal
of a cerebellar medulloblastoma 15 yr previously. The second patient had received
pituitary-derived growth hormone for treatment of growth hormone deficiency,
secondary to a third ventricle teratoma, exised 13 yr earlier. The presence of
cerebellar symptoms together with being recipients of growth hormone or dural
graft of cadaveric extraction arose suspicion of a diagnosis of CJD in both
individuals. Precautions in the anaesthetic and surgical management of these two
patients are discussed, and pertinent literature is reviewed briefly.
PMID- 9640163
TI - Minimally invasive coronary bypass surgery: postoperative pain management using
intermittent bupivacaine infiltration.
AB - Minimally invasive direct coronary artery bypass grafting (MIDCAB) is becoming a
popular adjunct to standard cardiac bypass surgery in selected patients with
accessible single or double vessel disease. However, the limited anterior
thoracotomy used to access the heart involves trauma to the muscle tissue during
removal of the fourth costal cartilage and a small piece of connected rib,
perhaps leading to more severe postoperative pain compared with patients
undergoing routine sternotomy. Intrathecal opioids can be used but have limited
therapeutic duration and there is concern regarding anticoagulation. We present a
case where soft tissue catheters were placed into the depths of the surgical
wounds and pain was diminished greatly by intermittent regular infiltration with
bupivacaine.
PMID- 9640164
TI - Error in measurement of oxygen and carbon dioxide concentrations by the
DeltatracII metabolic monitor in the presence of desflurane.
AB - In experiments in dogs on the metabolic effects of inhalation anaesthetics, we
noticed that in the presence of desflurane, oxygen uptake (VO2) measured with the
Deltatracll metabolic monitor seemingly increased whereas it decreased when
determined independently by the Fick principle. This difference remained even
after correction for changes in gas concentration on addition of an inhalation
anaesthetic. Therefore, we suspected that desflurane interferes with the
measurement of gas concentrations. Using different precision gases, we found that
desflurane disturbed both the paramagnetic oxygen sensor and the infrared carbon
dioxide detector so that the measured oxygen (when FIO2 was > 0.21) and carbon
dioxide concentrations were greater than expected. These errors multiply in the
computing process of oxygen uptake by the DeltatracII. When the DeltatracII is to
be used during inhalation anaesthesia, its results should be corrected for the
presence of an anaesthetic gas. More importantly, corrections must also be made
for measurement errors of the oxygen and carbon dioxide sensors, unless the
device has been equipped with a modified (nickel membrane) oxygen sensor
insensitive to the presence of volatile agents.
PMID- 9640165
TI - Video-intuboscopy: a new aid to routine and difficult tracheal intubation.
AB - Video-intuboscopy gives a video display of the view from the tip of the tracheal
tube during conventional laryngoscopy, and was developed particularly to assist
the immediate management of unexpected difficult intubation. A lightweight,
malleable video-optical intubation stylet transmits the view from the stylet tip
onto a monitor. It is inserted in the tracheal tube before starting anaesthesia,
and the view from the tracheal tube tip enables the anaesthetist to verify
tracheal tube position in the trachea. During difficult intubation the video view
is used to guide the tracheal tube into the trachea. When used to allow
confirmation of tracheal placement, the system did not interfere with
conventional intubation procedures. The method showed the subglottic airway, gave
immediate confirmation of tracheal tube position, and aided teaching and
supervision. The method was used to guide intubation in two patients with
unanticipated grade 3 laryngoscopic views. Intubation was simple, rapid and
atraumatic, without the need for head, neck or laryngeal manipulation. Tracheal
placement was instantly confirmed using the video view from the stylet tip.
Clinical studies are required to define the value of this new intubation
technique.
PMID- 9640166
TI - Stimulus frequency in the detection of neuromuscular block in humans. 1970.
PMID- 9640167
TI - Anaesthesia and the competence revolution.
PMID- 9640168
TI - Anaesthesia and the competence revolution.
PMID- 9640169
TI - Autologous blood transfusion.
PMID- 9640170
TI - Propofol and electrophysiological variables during emergence from anaesthesia.
PMID- 9640171
TI - Bronchospasm during inhalation of nebulized midazolam.
PMID- 9640172
TI - Low-dose naloxone in the treatment of urinary retention during extradural
fentanyl causes excessive reversal of analgesia.
PMID- 9640173
TI - Extradural catheter-related infections in patients with infected cutaneous
wounds.
PMID- 9640174
TI - Extradural catheter-related infections in patients with infected cutaneous
wounds.
PMID- 9640175
TI - Colour imaging using a scanning laser ophthalmoscope.
PMID- 9640176
TI - Macular holes--a diagnostic and therapeutic enigma?
PMID- 9640177
TI - Why "orbital pseudotumour" is no longer a useful concept.
PMID- 9640178
TI - Novel approach towards colour imaging using a scanning laser ophthalmoscope.
AB - AIMS: Conventional fundus imaging using a fundus camera produces colour fundus
pictures. The scanning laser ophthalmoscope (SLO) has the advantages of lower
levels of light exposure, improved contrast, and direct digital imaging but until
now has produced monochromatic images as a laser of single wavelength is used.
True representation of the fundus is possible by combining images taken using
blue, green, and red lasers. METHODS: A custom built SLO was used to capture
blue, green, and red fundus images from suitable volunteers and patients with
fundus disease. Images were corrected for eye movement and combined to form a
colour image. Colour fundus photographs were taken using a fundus camera for
comparison with the SLO image. RESULTS: The background fundus and retinal
vasculature had similar appearances with the two imaging modalities. Internal
limiting membrane reflections were prominent with the SLO. Identification of new
vessels in the diabetic fundus was easier with the SLO than the colour fundus
photographs. CONCLUSION: A colour SLO offers all the advantages of the present
monochromatic imaging system with the added advantage of true colour
representation of the fundus.
PMID- 9640179
TI - Fundus autofluorescence in patients with macular holes imaged with a laser
scanning ophthalmoscope.
AB - AIM: To demonstrate the usefulness of a recently developed technique of imaging
fundus autofluorescence and to compare it with the results of fluorescein
angiography in the diagnosis and staging of macular holes. METHODS: The intensity
and distribution of fundus autofluorescence was studied in 51 patients with
idiopathic macular holes and pseudoholes using a confocal laser scanning
ophthalmoscope (cLSO) and the images were compared with those obtained by fundus
fluorescein angiography. RESULTS: Autofluorescence imaging demonstrated bright
fluorescence of macular holes with appearance similar to that obtained by
fluorescein angiography. In contrast macular pseuodoholes showed no such
autofluorescence. The attached operculum in stage 2 macular holes and the
preretinal operculum in stage 3 macular holes showed focal decreased
autofluorescence. The associated retinal elevation and the cuff of subretinal
fluid were less fluorescent compared with the background autofluorescence of the
normal fellow eyes. Following successful surgical treatment the autofluorescence
of the macular holes was no longer visible. CONCLUSION: Autofluorescence imaging
with the cLSO makes the assessment of macular holes possible with an accuracy
comparable with that of fluorescein angiography. Being non-invasive and rapid,
autofluorescence imaging may become a useful alternative to fluorescein
angiography in the assessment and the differential diagnosis of full thickness
macular holes.
PMID- 9640181
TI - Comparison of measurements of neuroretinal rim area between confocal laser
scanning tomography and planimetry of photographs.
AB - BACKGROUND: To compare neuroretinal rim area measurements by confocal scanning
laser tomography and planimetric evaluation of optic disc photographs. METHODS:
For 221 patients with primary and secondary open angle glaucoma, 72 subjects with
ocular hypertension, and 139 normal subjects, the optic disc was morphometrically
analysed by the confocal scanning laser tomograph HRT (Heidelberg retina
tomograph) and by planimetric evaluation of stereo colour optic disc photographs.
RESULTS: Absolute rim area and rim to disc area were significantly (p < 0.0001)
larger with the HRT than with planimetric evaluation of photographs. Differences
between the two methods were significantly (p < 0.01) larger in normal eyes with
small cupping than in normal eyes with large cupping, and differences were
significantly (p < 0.01) larger in glaucomatous eyes with marked nerve damage
than in glaucomatous eyes with moderate nerve damage. Coefficients of
correlations between rim measurements of both methods were R2 = 0.60 for rim to
disc area and R2 = 0.33 for absolute rim area. Planimetric measurements of rim
area correlated significantly (p < 0.05) better than HRT determinations of rim
area with mean visual field defect and retinal nerve fibre layer visibility.
CONCLUSIONS: Measurements of absolute rim area and rim to disc area are
significantly larger with the HRT compared with planimetry of disc photographs.
Differences between both methods depend on disc area, cup size and glaucoma
stage. The reason may be that the HRT measures the retinal vessel trunk as part
of the neuroretinal rim. The differences between both methods, which should be
taken into account if disc measurements performed by both methods are compared
with each other, may not influence the main advantage of the HRT--that is,
morphological follow up examination of patients with glaucoma.
PMID- 9640180
TI - Quantitative evaluation of the optic nerve head in early glaucoma.
AB - AIMS: Progressive loss of neuroretinal rim tissue is known to occur early in
glaucoma and measurement of the neuroretinal rim area is possible by
magnification corrected analysis of optic disc photographs (planimetry). This
study was performed to determine whether the facility to distinguish between
glaucomatous and normal optic discs could be improved upon by: (a) taking into
account the known relation between optic disc size and neuroretinal rim area, and
(b) measuring rim area in a number of segments, in order to detect focal changes.
METHODS: Planimetric examination of the optic disc photographs of 88 control
subjects and 51 patients with early visual field defects was performed. In the
control group, multiple linear regression analysis was performed between
neuroretinal rim area and optic disc area, age, sex, eye side, refraction, and
keratometry. This was repeated for the whole disc and for each of twelve 30
degree segments. Normal ranges were defined by the 98% prediction intervals of
the regression analysis and the sensitivity and specificity for correct
identification of optic discs in the two groups determined. RESULTS: Multiple
linear regression demonstrated significant associations between the neuroretinal
rim area and optic disc area and age in normal subjects. Sensitivity and
specificity for glaucoma diagnosis, using the cut off derived from the 98%
prediction intervals, was 37.7% and 98.9% respectively when total neuroretinal
rim area alone was considered, and 88.7% and 94.3% respectively when the 30
degree segments were included. The most frequent pattern of neuroretinal rim loss
was diffuse, followed by thinning in more than one sector and then by thinning in
the inferotemporal sector alone. CONCLUSIONS: This method of optic disc analysis
enables the examiner to identify glaucomatous optic discs at the stage of early
perimetric loss with a high degree of precision. Optic disc photography is
simple, and fundus cameras are widely available. This method for glaucoma case
identification may therefore be suitable for the primary care setting as well as
hospital practice.
PMID- 9640182
TI - Optical coherence tomography of pneumatic displacement of optic disc pit
maculopathy.
AB - BACKGROUND: The authors have previously concluded that fluid from an optic disc
pit creates an inner layer separation (ILS) of the retina. An outer layer
detachment (OLD) centred on the macula is a secondary phenomenon that causes a
dense central scotoma. Pneumatic displacement of the OLD effects an improvement
in central vision. Pathology to confirm these conclusions is lacking.
Intraretinal images obtained by optical coherence tomography (OCT), however, are
confirmatory. METHODS: Three patients with optic disc pit maculopathy were
studied with stereoscopic photographs, visual fields, and OCT before and after
intravitreal gas was injected to displace the central retinal elevation to below
the inferior temporal vascular arcade. RESULTS: Preoperatively, OCT demonstrated
an ILS that connected with the optic disc pit. External to it was an OLD that
centred on the fovea and did not connect with the optic disc pit. Pneumatic
displacement of the OLD was accompanied by an improvement in central vision. Long
term follow up indicates that the effect of displacement may be temporary.
CONCLUSION: OCT confirmed the two layer structure of optic disc pit maculopathy
and that the improvement in central vision after pneumatic displacement coincides
with a reattachment of the OLD in the macula. It also supports the hypothesis
that the ILS, which persists, provides a conduit for the continuous flow of fluid
from the pit to the displaced retinal elevation.
PMID- 9640183
TI - An alternative and more cost effective method of delivery of radiotherapy in age
related macular degeneration.
AB - AIMS/BACKGROUND: In the past 5 years there has been a dramatic increase in the
use of radiotherapy to treat subfoveal neovascular membranes (NVMs) in both
Europe and the USA despite the high cost. An alternative, more cost effective
method of delivery using x ray simulation and bite block head fixation is
described. METHOD: 15 patients were recruited with classic subfoveal NVMs. Head
fixation was achieved with a customised Perspex mask for eight patients and a
bite block for seven. An x ray simulator was used to check the field of
irradiation. No computerised tomography (CT) was performed. All patients received
a total dose of 13.3 Gy ionising radiation. Visual acuities were charted before
and after treatment over a 24 month period. RESULTS: After 24 months, 5/8 (67%)
in the mask group showed stable visual acuities (less than two line change on
Snellen chart) compared with 3/7 (43%) in the bite block group. This difference
may be attributed to a variation in the pretreatment visual acuities in the two
groups. From several studies it has been estimated that 24 months after diagnosis
28% untreated individuals would have stable vision compared with 53% patients in
this study. CONCLUSIONS: These results compare favourably with other studies and
show that teletherapy can be safe and effective form of treatment for subfoveal
NVMs. The authors have described an alternative method of head fixation and shown
that CT scanning is not essential. This method of delivery is considerably less
costly than that traditionally used and may allow greater numbers of patients to
benefit from radiotherapy treatment.
PMID- 9640184
TI - Epithelial permeability reflects subclinical effects of contact lens wear.
AB - AIMS: Recently, it was reported by the authors that a single drop
fluorophotometric technique for estimating corneal epithelial permeability (Pde)
to fluorescein is not sufficiently precise for monitoring permeability changes in
individual patients., but may be useful for evaluating mean differences in Pdc in
population based research. To determine whether this technique provides a more
sensitive index of epithelial integrity compared with conventional clinical
assessments, the effects of mild corneal trauma on Pdc, the slit lamp appearance
of the cornea, and corneal thickness (CT) were assessed. METHODS: After baseline
slit lamp examinations (SLE) and CT measurements, one randomly chosen eye of each
of 32 normal subjects underwent 1 hour of closed eye soft contact lens (CL) wear
while the fellow eye served as a control (no CL). After removing the CL, the SLE
and CT measurements were repeated. Then, Pdc to fluorescein was assessed using a
single drop fluorophotometric method refined to enhance feasibility, precision,
and accuracy. RESULTS: The mean (95% confidence interval) difference in natural
log (Pdc) between 32 pairs of eyes (CL minus no CL) was 0.341 (0.069, 0.613), p =
0.016. By contrast, none of the 32 subjects exhibited corneal epithelial
disruption upon SLE with white light following the closed eye period. Also, no
substantial differences were apparent in the corneal swelling response between
paired eyes, mean delta CT (95% CI) = -2.31(-7.53, 2.91) microns, p = 0.37.
CONCLUSIONS: Pdc measurements, used in studies of modest sample size, appear
capable of detecting average differences in corneal barrier function that remain
undetectable by SLE or pachymetry.
PMID- 9640185
TI - Donor organ cultured corneal tissue selection before penetrating keratoplasty.
AB - AIMS: Donor organ cultured corneal tissue selection before penetrating
keratoplasty is carried out by taking into account different variables. The
objective was to identify preoperative variables which are significantly and
independently associated with transplant outcome and should effectively be taken
into account before transplantation. METHODS: 231 consecutive penetrating
keratoplasties were prospectively studied using organ cultured tissue.
Morphometric analysis of the donor corneal endothelium was performed before
transplantation. Graft survival and endothelial cell density, during the second
year following transplantation, were studied both at a univariate and
multivariate level. RESULTS: Recipient age, recipient rejection status, and
preoperative diagnosis significantly influenced graft survival. Graft survival
was higher when using corneal tissue from donors older than 80 years.
Postoperative endothelial density decreased with preservation time and
coefficient of variation after preservation. It increased with endothelial cell
density after preservation and deswelling time, and correlated with preoperative
diagnosis. CONCLUSION: Organ cultured corneas with endothelial cell density after
preservation < 2000 cells/mm2, and high coefficient of variation, may be
discarded before transplantation. Corneas should be preserved for less than 3
weeks, and allowed to deswell before transplantation for 2 or 3 days rather than
1 day.
PMID- 9640186
TI - Efficacy of probing as treatment of epiphora in adults with blocked nasolacrimal
ducts.
AB - AIMS: To determine the efficacy of probing in the initial treatment of epiphora
and the symptom free period in adults with blocked nasolacrimal ducts. METHODS:
The results of probing in 85 eyes with epiphora due to nasolacrimal duct
obstruction were studied retrospectively after a mean follow up of 7.4 months (SD
11.6) by a questionnaire and interview survey of patients. RESULTS: 35% of the
eyes had an outcome of no watering after probing, 17% mild watering, 35% moderate
watering, and 11% severe watering. The patients' satisfaction (watering
subjectively improved) after undergoing this procedure was 82%, which is higher
than previously reported. The mean symptom free period in eyes with no watering
was 11.25 months, in eyes with mild watering 8.20 months, in eyes with moderate
watering 5.35 months, and in eyes with severe watering 0.95 months. There was a
significant difference (p = 0.001) in the symptom free period between the no
watering and severe watering groups. CONCLUSIONS: Probing in adults with
confirmed nasolacrimal duct obstruction can be recommended as an initial
treatment procedure because of its relatively good efficacy and high patient
satisfaction without compromising subsequent surgical treatment if unsuccessful.
PMID- 9640187
TI - Open lacrimal surgery: a comparison of admission outcome and complications after
planned day case or inpatient management.
AB - AIMS: To assess the outcome, in terms of completion of admission and complication
rates, for two series of patients undergoing open lacrimal surgery, one group
planned for a day case admission and the other planned for inpatient stay.
METHODS: A retrospective analysis of case notes was performed for 200 patients
planned to have day case admission (for 209 open lacrimal operations) and the
details compared with those for 200 inpatient admissions (for 228 lacrimal
procedures) during the same period of study. The success rates for surgery were
not examined. RESULTS: 9% of planned day cases required overnight admission, 5.5%
for medical reasons and 3.5% for social or administrative reasons. There was a
similar incidence of postoperative complications in planned day cases and
inpatients, although 6% of day case patients developed postoperative cellulitis,
compared with 1.3% of the inpatients (p = 0.01). Overall, the incidence of
cellulitis was greater in cases complicated by intraoperative haemorrhage (p <
0.05) or the use of absorbable nasal packing (p < 0.0001). A similar number of
patients in each group attended the accident and emergency department before the
planned first postoperative clinic visit. CONCLUSION: Patients undergoing open
lacrimal surgery can be safely managed as day cases if carefully selected for
suitability on social and medical criteria. The use of general anaesthesia is
not, in itself, a contraindication to day case lacrimal surgery.
PMID- 9640188
TI - Trabeculectomy augmented with mitomycin C application under the scleral flap.
AB - AIM: The authors investigated the safety and intraocular pressure (IOP) lowering
effectiveness of trabeculectomy augmented with mitomycin C application beneath
the scleral flap, and assessed the influence of preoperative risk factors on the
surgical outcome. METHODS: A retrospective study of 72 consecutive high risk eyes
undergoing trabeculectomy with adjunctive mitomycin C (0.2 mg/ml) applied under
the scleral flap for 5 minutes was performed. Each eye was ascribed a score based
on the number of preoperative risk factors, and categorised into one of three
risk factor groups. Success was described as unqualified where IOP was < or = 21
mm Hg without medication and qualified where antiglaucomatous therapy was
required to maintain it at such a level. A life table analysis of IOP control was
calculated. RESULTS: The mean IOP (SD) fell from a preoperative level of 28.4
(6.9) to a level of 16.63 (8.06) mm Hg at the last follow up (paired Student's t
test: p < 0.0001). Fifty two eyes (72%) were classed as unqualified successes.
The survival rates did not differ significantly between different risk factor
groups (log rank test: chi 2 = 0.967, p > 0.1). The incidence of postoperative
complications compared favourably with reports of mitomycin C application between
Tenon's capsule and the undissected scleral bed. CONCLUSION: The results
illustrate that mitomycin C applied beneath the scleral flap during
trabeculectomy in high risk eyes is associated with a success rate comparable to
other modes of application. The incidence of potentially serious complications
such as conjunctival wound leak and prolonged hypotony was lower than previously
published data reporting sub-Tenon's administration of mitomycin C. The number
and nature of preoperative risk factors do not appear to influence the surgical
outcome. A possible mechanism of action is proposed.
PMID- 9640189
TI - Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure
and on blood-aqueous barrier permeability.
AB - AIM: To investigate the effect on intraocular pressure (IOP) and aqueous flare of
topical applications of latanoprost and dipivefrin alone or combined. METHODS: 22
patients with open angle glaucoma or ocular hypertension were included in a 4
week open label study. Median age was 68 years (range 50-79). They were allocated
to either 2 weeks' treatment with once daily evening administration of
latanoprost monotherapy (50 micrograms/ml) or twice daily dipivefrin monotherapy
(1 mg/ml), followed by 2 weeks' combination therapy with both drugs. RESULTS:
Latanoprost alone reduced IOP from 19.3 (SD 1.4) to 14.8 (0.9) mm Hg (p < 0.01).
Addition of dipivefrin caused a further reduction to 12.4 (0.9) mm Hg (p < 0.01
compared with latanoprost alone). In the group where the treatment started with
dipivefrin IOP was reduced from 22.3 (1.2) to 18.4 (1.0) mm Hg (p < 0.01) and
with the combination to 14.9 (0.9) mm Hg (p < 0.01). No change in aqueous flare
was observed with either drug, alone or in combination. A slight increase in
conjunctival hyperaemia was observed when the two drugs were combined.
CONCLUSIONS: Latanoprost and dipivefrin have an additive effect on IOP and no
clinically significant effect on the permeability to proteins of the blood
aqueous barrier. This implies that the two drugs can be a useful combination for
the treatment of glaucoma.
PMID- 9640190
TI - Diabetic retinopathy in Down's syndrome.
AB - AIM: To determine the prevalence of diabetic retinopathy in patients with Down's
syndrome and diabetes mellitus. METHODS: Nine patients with Down's syndrome and
diabetes mellitus were assessed. Factors recorded included type and duration of
diabetes, level of diabetic control, blood pressure, urinalysis, and results of
ophthalmological examination. RESULTS: The duration of diabetes ranged from 8 to
41 years (mean 17.6 years). All had satisfactory glycaemic control and blood
pressure measurements on the low side of normal (mean 106.6/70 mm Hg). One
patient had early background diabetic retinopathy. The remainder had no evidence
of diabetic retinopathy. CONCLUSION: The low prevalence of diabetic retinopathy
in these Down's syndrome patients, despite the long duration, is an interesting
finding. It suggests some inherent protective factor against the development of
diabetic retinopathy in this patient subgroup.
PMID- 9640191
TI - Use of eye care services by people with diabetes: the Melbourne Visual Impairment
Project.
AB - AIM: The use of eye care services by people with and without diabetes was
investigated in the Melbourne Visual Impairment Project (VIP), a population based
study of eye disease in a representative sample of Melbourne residents 40 years
of age and older. METHODS: A comprehensive interview was employed to elicit
information on history of diabetes, medication use, most recent visit to an
ophthalmologist and optometrist, and basic demographic details. Presence and
extent of diabetic retinopathy was determined by dilated fundus examination.
RESULTS: The Melbourne VIP comprised 3271 people who ranged in age from 40 to 98
years; 46.2% of them were male. Of 3189 people who had the fundus examination and
knew their diabetes status, 162 (5.1%) reported having been previously diagnosed
with diabetes and, of these, 37 (22.2%) were found to have diabetic retinopathy.
Seven people (4.3%) had developed diabetes before age 30. The mean duration of
diabetes was 9.2 years. People with diabetes were significantly more likely to
have visited an ophthalmologist ever or in the past 2 years than people without
diabetes. However, 31.8% of people with diabetes had never visited an
ophthalmologist. The proportion of people who had never seen an ophthalmologist
was 47.1% for people without diabetes, 34.2% for people with diabetes but without
diabetic retinopathy, and 25% for people with diabetic retinopathy. Sixty one per
cent of people with diabetic retinopathy had seen an ophthalmologist in the past
year and a further 3% within the past 2 years. People with diabetes were not
significantly more likely to have visited an optometrist than people without
diabetes (p = 0.51). Overall, 37.7% of people with diabetes and 32.9% of people
without diabetes had visited an optometrist within the past year (chi 2 = 2.25, 1
df, p = 0.13). Information concerning retinal examinations was available for 135
individuals (83.3% of people with diabetes). Only 74 (54.8%) could recall ever
having a dilated fundus examination; 10 (14%) by an optometrist, 62 (86%) by an
ophthalmologist, and five (7%) by a general practitioner. Of those 68 people who
had seen an ophthalmologist in the past 2 years, 48 (71%) reported a dilated
fundus examination during that time. This compares with 28 (43%) reported dilated
fundus examinations in the 65 people who had seen an optometrist in the past 2
years. This finding is statistically significant (chi 2 = 10.2, 1 df, p < 0.005).
CONCLUSION: These results indicate that nearly half of people with diabetes in
Melbourne are not receiving adequate screening or follow up for diabetic
retinopathy, despite universal health care.
PMID- 9640192
TI - A new computer program for mass screening of visual defects in preschool
children.
AB - AIMS: To test the effectiveness of a PC computer program for detecting vision
disorders which could be used by non-trained personnel, and to determine the
prevalence of visual impairment in a sample population of preschool children in
the city of Beer-Sheba, Israel. METHODS: 292 preschool children, aged 4-6 years,
were examined in the kindergarten setting, using the computer system and "gold
standard" tests. Visual acuity and stereopsis were tested and compared using
Snellen type symbol charts and random dot stereograms respectively. The
sensitivity, specificity, positive predictive value, negative predictive value,
and kappa test were evaluated. A computer pseudo Worth four dot test was also
performed but could not be compared with the standard Worth four dot test owing
to the inability of many children to count. RESULTS: Agreement between computer
and gold standard tests was 83% and 97.3% for visual acuity and stereopsis
respectively. The sensitivity of the computer stereogram was only 50%, but it had
a specificity of 98.9%, whereas the sensitivity and specificity of the visual
acuity test were 81.5% and 83% respectively. The positive predictive value of
both tests was about 63%. 27.7% of children tested had a visual acuity of 6/12 or
less and stereopsis was absent in 28% using standard tests. Impairment of fusion
was found in 5% of children using the computer pseudo Worth four dot test.
CONCLUSIONS: The computer program was found to be stimulating, rapid, and easy to
perform. The wide availability of computers in schools and at home allow it to be
used as an additional screening tool by non-trained personnel, such as teachers
and parents, but it is not a replacement for standard testing.
PMID- 9640193
TI - Comparison of decentration and tilt between one piece and three piece polymethyl
methacrylate intraocular lenses.
AB - BACKGROUND: The extent of the decentration and tilt was prospectively compared
between one piece polymethyl methacrylate (PMMA) and three piece PMMA intraocular
lenses (IOLs) which were implanted in the capsular bag after performing
continuous curvilinear capsulorhexis. METHODS: 91 patients underwent a one piece
PMMA IOL implantation in one eye as well as the implantation of the three piece
PMMA IOL with polyvinylidene fluoride loops in the opposite eye. The length of
the lens decentration and the angle of the tilt were quantitated using the
anterior eye segment analysis system (EAS-1000) at 1 week as well as 1, 3, and 6
months postoperatively. RESULTS: The mean length of the decentration in the one
piece IOL was smaller than that in the three piece IOL at 1 week (p = 0.0092), 1
month (p = 0.0044), 3 months (p = 0.0069), and 6 months (p = 0.0010)
postoperatively. However, no significant difference was found in the degree of
the tilt between the two types of IOLs throughout the observation periods.
CONCLUSION: These results clarified that the one piece PMMA IOL with rigid PMMA
haptics implanted in the capsular bag provides a better centration than the three
piece PMMA IOL with flexible haptics, whereas the tilt was the same between the
two types of IOLs.
PMID- 9640194
TI - Ocular complications of heart, lung, and liver transplantation.
AB - AIM: To document the nature and frequency of ocular complications in a large
group of patients who underwent heart, lung, or liver transplantation. METHODS: A
retrospective audit of the medical records of all patients undergoing heart,
lung, or combined heart-lung transplantation at St Vincent's Hospital, Sydney, or
liver transplantation at Royal Prince Alfred Hospital Sydney, was performed to
detect patients with symptomatic ocular complications following transplantation.
19 of 860 patients were identified as having ocular complications. RESULTS:
Ocular complications occurred in 2% of patients with 65% of these being
opportunistic infections. Herpes group viral retinitis (77%) and fungal
chorioretinitis (22%) were seen. Other complications included choroidal
pseudolymphoma, central retinal vein occlusion, herpes zoster ophthalmicus,
herpetic keratitis, dacryocystitis, cyclosporin retinopathy, and rifabutin
associated uveitis. CONCLUSION: Herpes group viral retinitis was the most common
ocular opportunistic infection and occurred most frequently during the second
year after transplantation. Delayed diagnosis was associated with poor visual
outcome.
PMID- 9640195
TI - Use of indomethacin for pain relief following scleral buckling surgery.
AB - BACKGROUND/AIMS: Patients undergoing scleral buckling and cryotherapy suffer from
mild to moderate postoperative pain. As good pain relief facilitates post
operative ocular examination, as well as patient comfort and recovery, the
authors designed a prospective randomised double masked trial to evaluate the
efficacy of indomethacin as a satisfactory analgesic for such patients. METHOD:
Patients with a primary uncomplicated rhegmatogenous retinal detachment requiring
scleral buckling and cryotherapy were randomly allocated to receive either
indomethacin or placebo. A rectal suppository was administered 2 hours before
surgery, followed by two capsules twice daily for 10 days. Pain relief was
assessed with a linear graphic rating scale at the end of each day. Supplementary
analgesia was allowed and recorded. RESULTS: 12 patients received indomethacin
(group A) and 16 received placebo (group B). The extent of surgery was similar in
both groups. One patient in group A, and two in group B withdrew after 3 days.
The pain scores were converted to changes from the baseline (score on day 1), and
the area under the curve calculated for each patient. The means of the areas were
analysed with the Mann-Whitney test and showed that indomethacin caused a
statistically significant reduction in pain score, both at 3 days (p = 0.04) and
at 10 days (p = 0.014). There was no statistically significant difference in
extra analgesic requirements between the two groups (p = 0.2). CONCLUSIONS:
Indomethacin is recommended for short to medium term pain relief following
scleral buckling and cryotherapy.
PMID- 9640197
TI - Vitreous intercellular adhesion molecule 1 in uveitis complicated by retinal
detachment.
AB - AIMS: The vitreous levels of soluble intercellular adhesion molecule 1 (sICAM-1)
were investigated in uveitic eyes undergoing vitrectomy for retinal detachment
(RD) or other complications, and the presence of this molecule was related to
disease activity and vitreous levels of the cytokine tumour necrosis factor alpha
(TNF alpha), known to upregulate ICAM-1 expression on various cells. METHODS:
Vitreous and serum samples from 23 patients with either active or quiescent
uveitis undergoing retinal surgery were examined for the levels of immunoreactive
sICAM-1 and TNF alpha by ELISA methods, and for the presence of biologically
active TNF alpha. Vitreous from non-uveitic eyes with rhegmatogenous retinal
detachment (RRD), macular holes or cadaveric eyes were used as controls. RESULTS:
As a whole, vitreous from uveitic eyes complicated or uncomplicated by RRD
contained significantly higher levels of sICAM-1 than vitreous from non-uveitic
eyes with RRD alone (p < 0.0005), eyes with macular holes (p < 0.0001), or normal
cadaveric vitreous (p < 0.0001). The proportion of vitreous containing > 20 ng/ml
sICAM-1 (> four times the normal values) was significantly higher in eyes with
uveitis complicated by RRD than in those eyes without RRD (Fisher's test, p =
0.02), and although levels of sICAM-1 were higher in eyes with active uveitis
than in those with quiet disease (p < 0.02), this could not be dissociated from
the increase caused by RRD. There was a relation between the vitreous levels of
sICAM-1 and those of immunoreactive TNF alpha (Spearman's correlation
coefficient; r = 0.601, p = 0.006), but not between the vitreous levels of sICAM
1 and those of biologically active TNF alpha. CONCLUSION: Increased vitreous
sICAM-1 levels and the association of this molecule with the presence of
immunoreactive TNF alpha in uveitic eyes confirm the operation of cytokine
mediated vascular reactions at the blood-retinal barrier during the development
of this condition. The persistence of high vitreous levels of sICAM-1 in eyes
with uveitis complicated by RRD despite previous immunosuppression may indicate a
low rate of clearance of inflammatory molecules from the vitreous cavity and an
exacerbation of the existing inflammatory process by the retinal detachment
itself.
PMID- 9640196
TI - Adhesion molecules in iris biopsy specimens from patients with uveitis.
AB - BACKGROUND/AIMS: Earlier studies on intraocular tissue have demonstrated that T
lymphocytes play a major role in the pathogenesis of uveitis. Adhesion molecules
are immunoregulatory molecules for the interaction between T lymphocytes and
vascular endothelium and they play an important role in the recruitment of
specific T lymphocytes from the circulation into inflamed tissue. In uveitis an
increased expression of some of these adhesion molecules may be expected.
METHODS: The presence of adhesion molecules was investigated in iris biopsy
specimens from 11 patients with uveitis and eight controls (patients with primary
open angle glaucoma) immunohistochemically with a panel of monoclonal antibodies:
LECAM (CD 62L), ICAM-1 (CD 54), LFA-1 (CD 11a/18), VCAM-1 (CD 106), VLA-4 (CD
49d), and HECA-452, a marker for high endothelial venules. RESULTS: Positive
staining for ICAM-1, LFA-1 and VCAM-1 was found in the iris in a significantly
higher number of uveitis patients than in controls. The remaining adhesion
molecules were also found in a higher number of uveitis patients than in
controls, but this difference did not reach statistical significance. CONCLUSION:
An increased expression of adhesion molecules was found in the iris of patients
with uveitis, indicating an immunoregulatory function for adhesion molecules in
the pathogenesis of uveitis.
PMID- 9640198
TI - Quantitative analysis of lipid deposits from Schnyder's corneal dystrophy.
AB - AIM: To report the quantitation of the lipid composition of a corneal button from
a Japanese woman in her 60s with clinically and histopathologically proved
Schnyder's corneal dystrophy. METHODS: Total lipids extracted from the corneal
button of the patient were analysed by the method of thin layer chromatography
flame ionisation detection. Two different solvent systems were used for neutral
lipid analysis and phospholipid analysis. Results were compared with three age
matched corneal buttons obtained from cadaveric eyes. RESULTS: The lipids that
accumulated in the cornea in Schnyder's dystrophy consisted mainly of
unesterified cholesterol and phospholipids. The analysis of phospholipids showed
sphingomyelin to be the predominant phospholipid in the patient's cornea.
CONCLUSION: Findings suggest that this disorder involves a disturbance of the
metabolism of cholesterol and/or sphingomyelin metabolism that is limited to the
cornea.
PMID- 9640199
TI - Long term growth arrest of human Tenon's fibroblasts following single
applications of beta radiation.
AB - AIMS/BACKGROUND: Antimetabolites are increasingly used to manipulate the healing
response after filtration surgery, but problems with thin cystic blebs have been
encountered with the liquid agents commonly used such as 5-fluorouracil and
mitomycin C. beta Radiation appears to be a useful adjuvant treatment for
preventing scarring after trabeculectomy, resulting in diffuse rather than cystic
bleb formation, but much of the basic cell biology of the ocular fibroblast
response to beta radiation remains unclear. The effects of beta radiation on
ocular fibroblast proliferation and cell cycling were investigated to determine
the nature and duration of these effects on these cells. METHODS: In vitro cell
culture techniques were used to investigate fibroblast proliferation. Cell
viability was studied using trypan blue dye exclusion. The effect of radiation on
cell cycling was investigated using bromodeoxyuridine uptake. p53 expression was
demonstrated using immunocytochemistry. RESULTS: beta Radiation inhibited
fibroblast proliferation in a dose dependent manner. Early cell death was not a
prominent feature, but irradiated fibroblasts demonstrated a rapid onset and
sustained period of growth arrest. p53 expression was found to be increased in
irradiated cells. CONCLUSIONS: Single doses of beta radiation significantly
inhibit Tenon's capsule fibroblast proliferation in vitro over a 28 day period.
This inhibition is the result of a rapid onset and sustained period of growth
arrest in irradiated cells. Irradiated fibroblasts show an increase in p53
expression, a nuclear phosphoprotein which has been associated with control of
the cell cycle. Single applications of beta radiation may be an effective
treatment for the prevention of bleb failure as a result of prolonged growth
arrest of Tenon's capsule fibroblasts.
PMID- 9640200
TI - Tear lipocalin and the eye's front line of defence.
PMID- 9640201
TI - Cystoid macular oedema in patients with AIDS and cytomegalovirus retinitis on
highly active antiretroviral therapy.
PMID- 9640202
TI - Aicardi syndrome.
PMID- 9640203
TI - Paucity of signs in X linked ocular albinism with a 700 kb deletion spanning the
OA1 gene.
PMID- 9640204
TI - Intracranial plasmacytoma masquerading as Gradenigo's syndrome.
PMID- 9640205
TI - Use of ultrasound biomicroscopy in the localisation and management of an
anteriorly situated intraocular foreign body.
PMID- 9640206
TI - Intravitreal phaco chopper fragment missed by computed tomography.
PMID- 9640207
TI - Absence of relative afferent pupillary defect and pupillary hemiakinesia in a
child with homonymous hemianopia due to ((retro-)geniculate) porencephaly.
PMID- 9640208
TI - Expression of transforming growth factor beta superfamily and their receptors in
the corneal stromal wound healing process after excimer laser keratectomy.
PMID- 9640209
TI - Quality of life and breast cancer--the learning curve never ends.
PMID- 9640210
TI - Should cancer patients with incurable disease receive parenteral or enteral
nutritional support?
PMID- 9640211
TI - Irinotecan and 5-fluorouracil in colorectal cancer: time for a pause?
PMID- 9640212
TI - Electronic biomedical journals: how they appear and what they offer.
AB - This study, prompted by a number of articles presaging the imminent demise of
biomedical journals due to the rise of their electronic spread, analysed 54 Web
sites of the journals included in the Oncology section of the Science Citation
Index, Journal Citation Reports (1994) and the sites of 10 other leading
digitised biomedical journals. The aim was to determine quantitative and
qualitative differences in terms of information content existing between the two
media. The analysis confirmed that there are limits to the information contained
in the scientific journals currently on the Internet and upholds the authors'
conclusion that, in the oncology field, the printed journal will continue to have
an important role for most individual users for some time.
PMID- 9640213
TI - Comparison of 5-fluoro-2'-deoxyuridine with 5-fluorouracil and their role in the
treatment of colorectal cancer.
AB - Despite more than 30 years of intensive studies on new drugs against advanced
colorectal cancer, the fluoropyrimidines remain the drugs of choice for systemic
treatment and for hepatic artery infusion (HAI). This overview describes new
developments in advanced colorectal cancer chemotherapy, providing a rationale
for more effective use of the fluoropyrimidines, with biochemical modulation,
scheduling or by revealing biochemical mechanisms of action that correlate with
antitumour activity. In human colorectal cancer cell lines and various animal
tumour model systems 5-fluoro-2'-deoxyuridine (FdUrd) is more effective than 5
fluorouracil (5-FU). Comparably, FdUrd's modulation by leucovorin (LV) is more
potent than 5-FU. In animal studies it is shown that intermittent high-bolus
administration of FdUrd generates better antitumour activity, compared with equal
toxic doses or any other schedule of 5-FU. These effects are related to prolonged
thymidylate synthase (TS) inhibition and the prevention of TS induction, rather
than RNA incorporation. Preclinical studies with modulators such as N
phosphonacetyl-L-aspartate (PALA), WR-2721, mitomycin C and platinum derivatives
provide a rationale for clinical use in the future. The first choice systemic
chemotherapy of patients with advanced colorectal cancer remains 5-FU combined
with LV. Some improvement in therapeutic efficacy has been achieved with
locoregional HAI. In randomised studies HAI FdUrd improves the quality of life
and survival as compared with optimal systemic therapy. Chronomodulation
decreases toxicity, allowing dose intensification, while modulators such as LV or
dexamethasone increase survival of patients treated with HAI FdUrd to 86% after 1
year. In conclusion, the clinical use of FdUrd has not been fully explored.
Intermittent high-dose FdUrd, chronomodulation together with the use of
modulators or drugs focused on prolonged TS inhibition, should be studied in
large randomised studies.
PMID- 9640214
TI - Quality of life of early-stage breast cancer patients treated with radical
mastectomy or breast-conserving procedures: results of EORTC Trial 10801. The
European Organization for Research and Treatment of Cancer (EORTC), Breast Cancer
Co-operative Group (BCCG).
AB - In 1980 the EORTC-BCCG initiated a multicentre randomised clinical trial
comparing modified radical mastectomy (MRM) with breast-conserving therapy (BCT)
in stage I and II breast cancer. The main endpoint of the trial was survival. A
brief quality of life (QoL) questionnaire consisting of two multi-item scales
(body image and fear of recurrence) and two single items (satisfaction with
treatment and cosmetic result) was included in the trial. A cosmetic evaluation
of the breast after conservative surgery was also performed. This report
concentrates on the results of the QoL study and the cosmetic evaluation.
Multitrait scaling analysis was employed to verify the hypothesised scale
structure of the questionnaire. Treatment comparison of the QoL scores at 2 years
post-treatment was performed using a stratified Wilcoxon rank sum test. Both
patients' and doctors' ratings of the cosmetic result were documented on the
clinical follow-up form. A multivariate analysis was performed to identify which
factors influenced the cosmetic outcome. In total, 127 patients in the MRM arm
and 151 in the BCT arm completed a QoL questionnaire at approximately 2 years
after randomisation (months 25-36). The Cronbach's alpha coefficients were 0.79
and 0.73 for the body image and fear of recurrence scales, respectively.
Significant benefit in body image and satisfaction with treatment was observed in
the BCT patients. No significant difference was observed in fear of recurrence
between the two groups. Ratings of cosmetic results decreased with time, in line
with clinical observations of long-term side-effects of radiotherapy. Wide
excision appeared to be the most important predictive factor for poor cosmetic
result. In this multicentre randomised study, BCT helped to maintain the
patients' body image, resulted in higher satisfaction with treatment and yielded
no significant difference from MRM with respect to fear of recurrence.
PMID- 9640215
TI - Eight-year results of a prospective non-randomised study on therapy of small
breast cancer. The German Breast Cancer Study Group (GBSG).
AB - In this report, the results of the first controlled clinical trial on breast
cancer in Germany, begun in 1983, are presented after a median follow-up of 8
years. Four-year results have been previously published. In pT1 N0 M0 breast
cancer, mastectomy as the standard treatment was to be compared with tumorectomy
plus radiotherapy to the remaining breast tissue. The study design, originally
planned as a comprehensive cohort study including randomised and non-randomised
patients, had to be changed into a prospective observation study due to the low
randomisation rate. 1036 out of 1119 recruited patients were evaluable. After a
median follow-up of 97 months, 237 events (local recurrence, regional recurrence,
distant metastases, contralateral breast cancer or death of the patient without
previous recurrence) occurred. With the exception of death without recurrence,
the events were evenly distributed among the two treatment groups. The 8-year
local recurrence rate of the whole patient population is 8.8%. Out of all
prognostic factors examined, only tumour size and grade had a significant
influence on recurrent disease. Event-free survival decreased in cases with
'uncertain' tumour margins, whereas the width of the margin has no influence on
disease recurrence. Based on 151 deaths observed so far, there was no significant
difference in overall survival between the two treatment groups. The 8-year
results of this study are in accordance with the 4-year results reported
previously and with those of other breast-conserving treatment trials. There was
no significant difference between the two treatment groups with regard to event
free and overall survival. Incomplete tumorectomy had a negative influence on
recurrence.
PMID- 9640216
TI - The use of complementary therapies by breast cancer patients attending
conventional treatment.
AB - The aim of this study was to measure the proportion and characteristics of
complementary therapy (CT) users among female breast cancer patients receiving
conventional treatment. 473 women who had received surgical intervention for
breast cancer in the year of diagnosis were sent a questionnaire for completion,
and 242 responded. CT had been used by 16.5% after cancer diagnosis, only 8.7%
before. The most commonly used CTs were homeopathy, manual healing method,
herbalism and acupuncture. The main reason for using CTs was physical distress.
Only a minority was searching for psychological support. 24 users were satisfied
with these treatments, and two-thirds would suggest them. Users were
significantly younger, more educated, and previous users of CTs than non-users.
Adjusting each variable for the effect of the others, only previous use had an
independent effect on increasing the probability of being users after cancer
diagnosis.
PMID- 9640217
TI - Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients.
AB - Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently
recognised as a distinct disease entity. Little is known about the prognostic
factors and optimal treatment of MCL. The aim of this study was to analyse
retrospectively the clinical features and effect of treatment in 94 MCL patients
diagnosed and treated in one centre between 1980 and 1996, and to find out
different factors influencing the treatment results and prognosis. The median age
of the patients was 66 years, and 77% were over 60 years old. Of the patients,
76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B
symptoms were present in 35% of the cases. Bone marrow infiltration was found in
61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved
complete remission with first- or second-line therapy. The median duration of
remission, time to treatment failure (TTF), and survival were 28, 18, and 41
months, respectively. In multivariate analyses, age, stage and leukaemic disease
were significantly associated with TTF, and age, stage, leukaemic disease and
lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL.
None of the conventional chemotherapies seems curative. A prospective randomised
trial should be made to evaluate the benefit of anthracycline-containing regimens
in MCL.
PMID- 9640218
TI - Vessel counts and vascular endothelial growth factor expression in pancreatic
adenocarcinoma.
AB - Angiogenesis is essential for growth and metastasis of solid malignancies. In
several tumours, tumour vessel count and expression of vascular endothelial
growth factor (VEGF), a potent angiogenic factor, have been associated with
prognosis. To determine if vessel count and VEGF expression are prognostic
factors in pancreatic cancer, we examined these parameters in resected tumour
specimens from 22 patients who did not receive pre-operative therapy. Paraffin
embedded tumour specimens were immunohistochemically stained for factor VIII
(surrogate for vessels) and VEGF. Vessel counts and VEGF expression were
evaluated without knowledge of patient outcome. The median follow-up for the
entire group had not been reached as of 23.1 months (range 10-69 months). The
mean vessel count and VEGF expression were no different between those patients
who had recurrences and those who did not. By linear regression analysis, the
correlation of VEGF expression with vessel count did not reach statistical
significance (P = 0.0685). Survival and time to recurrence were similar in
patients with high and low vessel counts and VEGF expression of 1, 2 or 3. Tumour
differentiation or lymph node positivity had no effect on either VEGF expression
or vessel count. Our data suggest that, in contrast to findings in other solid
malignancies, vessel count and VEGF expression are not predictors of survival or
recurrence in patients with resectable adenocarcinoma of the pancreas.
PMID- 9640219
TI - Long-term survival following neoadjuvant chemotherapy and radical surgery in
locally advanced cervical cancer.
AB - The aim of this study was to analyse the long-term survival and the relationships
between prognostic factors at presentation, chemoresponsiveness and disease
outcome in patients with locally advanced cervical cancer treated by neoadjuvant
chemotherapy and radical surgery (RS). Two consecutive studies of neoadjuvant
chemotherapy containing cisplatin, bleomycin plus/minus methotrexate followed by
radical hysterectomy and systematic aortic and pelvic lymphadenectomy were
carried out between January 1986 and September 1990 on 130 patients with > or = 4
cm stage IB2-III cervical cancer. Survival analysis was performed using the
Kaplan and Meier test and Cox's multivariate regression analysis. 128 (98%) of
the patients enrolled were evaluable for clinical response and survival, 83%
(106) of the patients responded to chemotherapy, with a 15% complete response
rate. Logistic regression analysis demonstrated that International Federation of
Gynecology and Obstetrics (FIGO) stage, cervical tumour size, parametrial
involvement and histotype are highly predictive of response. Responding patients
underwent laparotomy, but 8% were not amenable for radical surgery. The 10-year
survival estimates were 91%, 80% and 34.5% for stage IB2-IIA bulky, IIB and III,
respectively (P < 0.001). After Cox's regression analysis, the parameters
significantly associated with survival were the same factors predicting response
to neoadjuvant chemotherapy. No stage IB2-IIA bulky patient has so far relapsed,
while 12% stage IIB and 56% stage III patients recurred. The 10-year disease-free
survival estimates are 91% and 44% for stage IB2-IIB and III, respectively (P <
0.001). Metastatic nodes and persistent tumour in the parametria were the only
two independent factors for disease-free survival after multiple regression
analysis. After a long-term follow-up (median follow-up 98 months (20-129+)), our
results give new evidence of the prognostic value of response to neoadjuvant
chemotherapy and of a possible therapeutic benefit of the sequential treatment
adopted which, however, must be verified in a randomised setting.
PMID- 9640220
TI - Initial management of primary mediastinal seminoma: radiotherapy or cisplatin
based chemotherapy?
AB - Primary mediastinal seminoma is an uncommon neoplasm, the optimal management of
which is still debated. Radiotherapy produces a 65% disease-free survival rate.
We assess whether these results have been improved with the advent of cisplatin
based chemotherapy. Data from 14 patients treated at the Institut Gustave-Roussy
were reviewed. 9 had received cisplatin-based chemotherapy (Group 1): their
outcome was compared with that of 5 patients treated with radiotherapy without
chemotherapy (Group 2). We also reviewed data from the English literature using
strict criteria, and report results concerning patients who received cisplatin
based chemotherapy and those who received radiotherapy. 8 of the 9 patients (89%)
in Group 1 are long-term disease-free survivors and only 3 of 5 patients in Group
2. The patient who died in Group 1 was the only one who refused surgical
resection of residual masses after chemotherapy. The review of the literature
revealed that 59 of 68 (87%) patients initially managed with cisplatin- or
carboplatin-based chemotherapy and for whom sufficient data are available, are
long-term survivors and free of disease. Some of these patients had also received
radiotherapy. Only 64 of 103 (62%) treated with thoracic radiotherapy without
chemotherapy were long-term disease-free survivors. The disease-free survival
rate of 51 patients who received cisplatin-based chemotherapy (excluding those
who received carboplatin) was 86%. The difference in survival between patients
administered cisplatin-based chemotherapy and those who underwent radiotherapy is
apparently not due to unbalanced prognostic factors, the effect of time or non
specific medical management. We conclude that cisplatin-based chemotherapy allows
long-term disease-free survival in approximately 85% of patients. These results
seem to be higher than those obtained without cisplatin-based chemotherapy.
However, a randomised study is required for definitive conclusions, but it is
very unlikely that such a study will be performed due to the rarity of this
neoplasm. Another alternative would be a meta-analysis based on individual data.
PMID- 9640221
TI - Cisplatin-based chemotherapy in advanced seminoma: the Institut Gustave Roussy
experience.
AB - The aim of this study was to report the results of cisplatin-based combination
chemotherapy for patients with pure seminomatous tumours. 72 patients with
advanced seminoma were treated with various cisplatin-based chemotherapy
regimens. 61 (85%) patients achieved a sustained durable response. 11 relapses
were observed with a median time to failure of 6 months. Overall, 60 (83%) of the
72 patients remain alive and free of disease after a median follow-up of 64
months. Initial clinical (age, site of primary, prior radiotherapy, extent of
disease) and biological (serum human chorionic gonadotrophin levels, serum lactic
dehydrogenase levels, p53 immunostaining) features which could be of predictive
value for survival, were analysed in a univariate analysis. No variable retained
statistical significance. High cure rates are expected after chemotherapy with
standard cisplatin-based combinations in advanced seminoma. Renewed efforts are
required to identify markers of chemosensitivity.
PMID- 9640222
TI - Non-Hodgkin's lymphoma.
PMID- 9640223
TI - Recombinant human erythropoietin in the prevention of chemotherapy-induced
anaemia in children with malignant solid tumours.
AB - This prospective, randomised pilot study was designed to evaluate safety,
feasibility and efficacy of recombinant human erythropoietin (rhEPO) in the
prevention and treatment of chemotherapy-induced anaemia in children with solid
tumours. 20 children (age 4-18 years) undergoing cyclic combination chemotherapy
were randomised either to a control group or to receive rhEPO at a dose of 150
U/kg/dose subcutaneously three times/week for a minimum of 12 weeks or three
chemotherapy cycles. Of 15 evaluable patients, 8 were randomised to the rhEPO
group and 7 to the control group. RhEPO-treated patients showed an increase in
the haematocrit over the first 8 weeks of therapy, with a significantly higher
mean haematocrit at week 8 (33.2 +/- 2.1% versus 39.3 +/- 4.2% in the control and
rhEPO groups, respectively, P < 0.05). Similarly, significantly higher
haemoglobin concentrations could be demonstrated in the rhEPO group by week 8
(11.06 +/- 1.35 g/dl versus 13.11 +/- 1.13 g/dl in the control and rhEPO groups,
respectively, P < 0.05), with higher precycle haemoglobin before chemotherapy
cycles 3 and 4 and higher midcycle haemoglobin between cycles 3 and 4. There was
a trend towards a reduction of transfusion requirements during the 3rd month of
therapy in rhEPO patients. The results of this pilot study indicate a significant
benefit of rhEPO in children treated with intensive combination chemotherapy
regimens. Further studies should target issues such as appropriate dosing, timing
and duration of rhEPO therapy in children with cancer.
PMID- 9640224
TI - BRCA1-positive patients are small for gestational age compared with their
unaffected relatives.
AB - The BRCA1 gene is thought to exert its main function early in life. We,
therefore, studied the effects of BRCA1 mutations on birth weight and birth
length. This was carried out by comparing 33 women with and without mutations.
Birth weight and length were obtained from a self-administered questionnaire.
BRCA1 mutations carriers had a significantly lower birth weight (P = 0.0041)
compared with non-carriers, after adjustment for gestational age. They were also
significantly shorter at birth compared with their unaffected relatives (P =
0.0060), after adjustment for gestational age. The BRCA1 gene thus seems to
influence the carriers in utero. The findings could imply that humans
heterozygotic for the BRCA1 mutations may be influenced by the mutations during
development in utero.
PMID- 9640225
TI - Survival of breast cancer patients in Lithuania and Norway, 1988-1992.
AB - In Norway, the incidence of breast cancer is almost twice that in Lithuania,
whereas the mortality rates of the disease are approximately the same in both
countries. The aim of the present study was to compare the survival of breast
cancer patients in the two countries according to stage. The material from both
countries included cases diagnosed between 1988 and 1992 with complete follow-up
of date of death to the end of 1995. The Norwegian data consisted of all 9403 new
cases recorded by the Norwegian Cancer Registry. The Lithuanian data included in
all 1649 new cases treated at the Oncology Centre in Vilnius, which represents
40% of breast cancer cases in Lithuania--these cases had the same distribution of
the disease by age and stage as for the whole country. The overall 5-year
relative survival was lower in Lithuania (57.3%) than in Norway (78.4%). Lower
survival was observed in Lithuania compared with Norway for all stages. In stage
I, the difference was 7.8% in absolute terms which could be explained by a higher
proportion of small tumours among the Norwegian cancer cases (63.7% of tumours
were 2 cm or less, while in Lithuania the proportion of small stage I tumours was
only 27.9%). Therefore, early diagnosis within the stage I category seems
relevant. The difference in survival was, however, most pronounced in stage II
(20%) and III (29%). In Norway, the better overall survival is partly explained
by a more favourable stage distribution. The lower survival of Lithuanian cases
within stage categories could be explained by more advanced metastases to
regional lymph nodes and by higher proportions of large tumours within stage.
PMID- 9640226
TI - No predictive value of the micronucleus assay for patients with severe acute
reaction of normal tissue after radiotherapy.
AB - In approximately 5% of cancer patients undergoing radiotherapy, this treatment
has to be interrupted because of an acute reaction of normal tissues. To test the
possibility of predicting this type of reaction, the micronucleus assay was used
to determine radiosensitivities of peripheral blood lymphocytes of 15 patients
with severe acute reaction of normal tissue, 15 patients without this reaction
and 15 healthy donors. Whole-blood cultures were irradiated with X-rays (4 Gy,
1.08 Gy/min) and treated with cytochalasin B. The micronuclei scores observed in
irradiated cells were corrected for the scores in unirradiated cells. Intra
individual and interindividual variations in micronuclei scores were analysed in
samples from healthy donors, and highly significant interindividual differences
were found (P < 0.001). Scores of cells not irradiated in vitro were higher for
cancer patients before radiotherapy than for healthy donors (P < 0.001), and
those for cancer patients after radiotherapy were higher than for patients before
radiotherapy (P < 0.001). Average micronuclei scores induced by in vitro
irradiation were significantly higher in samples from cancer patients compared
with those from healthy donors (P < 0.01). Moreover, all subgroups of cancer
patients included individuals with very high levels of micronuclei after in vitro
irradiation. There was, however, no relationship between the micronuclei scores
and the occurrence of severe acute reactions in normal tissues.
PMID- 9640227
TI - Antitumour activity and schedule dependency of 8-chloroadenosine-3',5'
monophosphate (8-ClcAMP) against human tumour xenografts.
AB - 8-Chloroadenosine-3',5'-monophosphate (8-ClcAMP) is a novel antitumour agent
currently undergoing phase I clinical trials in several European centres. In this
study, its antitumour activity against human tumour xenografts and its dependence
on schedule were investigated. When administered by continuous infusion at doses
of 100 or 50 mg/kg/day to nude mice bearing human tumour xenografts, 8-ClcAMP
inhibited the growth of the HT 29 colorectal, ZR-75-1 breast, HOX 60 and PE04
ovarian and PANC-1 pancreatic carcinoma xenografts. However, these infusion
schedules produced hypercalcaemia and severe weight loss. In an attempt to
optimise antitumour activity and minimise toxicity, several other schedules were
studied. In comparison with continuous administration of 8-ClcAMP at 50 mg/kg/day
for 14 days which, although producing complete growth inhibition in the HOX 60
model, was associated with a marked body weight loss, schedules in which the
infusion was interrupted (infusion on either days 0-4; 7-11 or days 0-2; 6-8)
produced minimal weight loss but also reduced antitumour activity. However, co
administration of salmon calcitonin with continuous infusion of 8-ClcAMP
prevented both hypercalcaemia and body weight loss in 3/6 animals while still
producing marked inhibition of tumour growth. These data indicate that 8-ClcAMP
has broad-spectrum antitumour activity and the major side-effect of
hypercalcaemia may at least in part be ameliorated by the use of salmon
calcitonin.
PMID- 9640228
TI - 3,3',4,4'-tetrachlorobiphenyl (TCB) can enhance DMBA-induced mammary
carcinogenesis in the rat.
AB - Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants which
can be stored in the fatty tissue of breast and secreted in milk. Previous
studies have shown that PCBs can influence liver carcinogenesis in animal models
but no such studies have been reported in breast. These experiments aimed to
determine whether a PCB congener could influence mammary carcinogenesis using the
rat DMBA-induced mammary tumour model system. 3,3',4,4'-Tetrachlorobiphenyl (TCB)
enhanced the development of DMBA-induced mammary tumours in young female rats and
did so in animals fed either a low-fat (5% w/w corn oil) or a high-fat (20% w/w
corn oil) diet. The combination of TCB and high-fat diet resulted in tumours
growing so fast that the experiment had to be terminated at 10.5 weeks for humane
reasons. At termination the total numbers of tumours in each group of 20 rats
were: 4 in the low-fat group, 22 in the low-fat plus TCB group, 25 in the high
fat group and 50 in the high-fat plus TCB group. Histopathological analysis
confirmed that 98% of the tumours were mammary carcinomas, predominantly in situ
ductal carcinomas, but, in addition, revealed that 13 of the tumours had an
invasive phenotype of which 12/13 had all arisen in TCB-treated animals. This
demonstrates, for the first time, that a PCB congener can influence mammary
carcinogenesis.
PMID- 9640229
TI - Serum levels of intercellular adhesion molecule 1 (ICAM-1) in patients with
colorectal cancer: inhibitory effect on cytotoxicity.
AB - A positive correlation between the level of ICAM-1 in serum and the stage of
neoplastic processes has been demonstrated. We studied ICAM-1 serum concentration
in 27 colorectal cancer patients and investigated the effect of this molecule on
cellular aggregation and toxicity. ICAM-1 serum concentration in the group of
patients was significantly higher (P < 0.01) than in normal controls and was
related to tumour stage. Patient sera inhibited both the formation of cellular
aggregates and the percentage of specific lysis, the effect being lost when the
serum was depleted of ICAM-1. These results suggest that the release of soluble
ICAM-1 may represent a mechanism of tumour escape.
PMID- 9640230
TI - Dipeptidyl peptidase III in malignant and non-malignant gynaecological tissue.
AB - Exopeptidases, in contrast to endopeptidases (proteinases) have been much less
studied in relation to cancer. The aim of this study was to investigate one such
enzyme, dipeptidyl peptidase III (DPP III), in gynaecological tissues, by
measuring both the enzyme activity and enzyme content. DPP III activity was
assessed in normal (n = 65), benign (n = 9) and malignant (n = 51) gynaecological
tissues. A statistically significant higher DPP III activity was observed in
endometrial (n = 40, P = 4.6 x 10(-7)) and ovarian (n = 11, P = 8.1 x 10(-4))
malignant tumours, whereas no significant difference was detected for leiomyomas
(n = 8), if compared to the activity in normal tissue. A matched pair analysis of
normal and cancerous endometrial tissue confirmed the significance of the DPP III
activity increase in the transformed tissue (n = 7, P = 0.022). Western blot
analysis revealed a significantly (P = 0.014) increased level of DPP III in
endometrial cancer. Further, regression analysis showed a positive correlation
between the activity and the content of DPP III in normal tissue (r = 0.637, P =
0.047) and in endometrial cancer (r = 0.574, P < 0.007). The increase of the DPP
III activity was observed in the endometrial carcinomas of various histological
types, grade or the depth of myometrial invasion. The easy-to-perform
determination of this exopeptidase activity may serve as a potential indicator of
endometrial and ovarian malignancies.
PMID- 9640231
TI - Potentiated antitumour effects of cisplatin and lovastatin against MmB16 melanoma
in mice.
AB - Lovastatin, the drug used in the treatment of hypercholesterolaemia, has
previously been reported to exert synergistic antitumour activity in a melanoma
model in mice when used together with some immune response modifiers. In this
study, we examined the antitumour effect of cisplatin augmented by its combined
application with lovastatin, both in vitro and in vivo, in a murine melanoma
model. The results of this study suggest that lovastatin may enhance the
therapeutic effects of cisplatin in the treatment of malignant melanomas.
PMID- 9640232
TI - Pharmacokinetics of cisplatin with and without amifostine in tumour-bearing nude
mice.
AB - Amifostine (Ethyol, WR-2721) is in use in the clinic as a protector against
platinum-induced toxicities. We have previously reported that amifostine induced
a potentiation of the antitumour activity of carboplatin in human ovarian cancer
xenografts. An influence of amifostine on the pharmacokinetics of carboplatin,
resulting in higher platinum concentrations in plasma and tissues of the tumour
bearing nude mice, was thought to be the cause of enhancement of the antitumour
activity. Therefore, the pharmacokinetics of cisplatin were investigated in
tumour-bearing nude mice treated with cisplatin alone or in combination with
amifostine. A significant increase in the area under the curve (AUC) of the total
platinum concentration in mice treated with amifostine was only observed in the
kidney (from 355 to 398 nmol h/g), whereas in the other tissues and plasma no
significant changes were measured. The selective protection of normal tissues by
amifostine was confirmed by a decrease in the AUC of the cisplatin-DNA adduct
levels in normal tissues. The decrease was only significant in the liver (282-240
fmol h/microgram DNA), whereas in tumour tissue a slight increase in the AUC of
the cisplatin-DNA adducts could be detected (91.3-110.1 fmol h/microgram DNA).
The minor influence of amifostine on the pharmacokinetics of cisplatin may be the
reason why amifostine did not potentiate the antitumour activity of cisplatin.
The influence of amifostine on cisplatin-DNA adduct levels in normal tissues
versus tumour tissues is further evidence for the usefulness of this toxicity
modulator in cancer patients.
PMID- 9640233
TI - Identification of a new commonly deleted region within a 2-cM interval of
chromosome 11p11 in breast cancers.
AB - Allelic loss has been observed on the short arm of chromosome 11 in a variety of
human cancers. We have examined 184 breast cancers for allelic loss anywhere in
chromosome 11p, using 15 well-spaced microsatellite markers. Allelic loss was
observed in 86 cases (47%) and a new commonly deleted region 2-cM in length was
identified at 11p11 between loci D11S986 and D11S1313, in addition to a 12-cM
region of a common deletion at 11p15.5. A significant association was found
between allelic loss on 11p15.5 and LOH on 11p11 and the loss of progesterone
receptors.
PMID- 9640234
TI - Results of a phase II trial with second-line cystemustine at 60 mg/m2 in advanced
soft tissue sarcoma: a trial of the EORTC Early Clinical Studies Group.
AB - The aim of this phase II trial was to examine the efficacy of a new nitrosourea,
cystemustine, in soft tissue sarcoma. Between January 1990 and March 1991, 32
pretreated patients with advanced soft tissue sarcoma were enrolled. Cystemustine
was given every 2 weeks at 60 mg/m2 via a 15-min i.v. infusion. All eligible
patients were considered evaluable for response and toxicity (WHO criteria). Of
the 32 enrolled patients, 4 were ineligible, leaving 28 evaluable patients. All
but 1 had been pretreated: 6 with adjuvant chemotherapy, 18 patients with first
line palliative chemotherapy without nitrosourea, 3 with both treatments, and 18
had received radiotherapy. Median age was 54 years (range 20-73) and median
performance status was 1 (0-2). One partial response (PR, duration 12 weeks), 2
stable disease and 25 progressions were observed, giving an overall response rate
of 3.57% (confidence interval: 0.1-18.4%). Toxicity was mild, and was mainly
neutropenia (no grade 3 or 4), thrombocytopenia (3.57% grade 3 and grade 4) and
nausea-vomiting (no grade 3 or 4). It should be noted that the treatment for the
patient who obtained a PR was third line with no previous response. Cystemustine
with this schedule appears to have a low clinical activity and toxicity in
advanced soft tissue sarcoma.
PMID- 9640235
TI - alpha-Melanotropin immunoreactivity in human melanoma exudate is related to
necrosis.
AB - We have previously reported high immunoreactive alpha-MSH (IR-alpha-MSH)
concentrations in melanoma patients' plasma, as well as significant amounts in
melanoma metastases and cells grown in culture. Necrosis within the melanoma
tumour leads to a massive proteolysis of intracellular proteins and release of
cell content: this might significantly contribute to the elevated IR-alpha-MSH
plasma levels measured in melanoma patients. To test this hypothesis, we studied
the necrosis-related release of MSH from human melanoma cells, using a specific
radioimmunoassay. The studies of fine-needle biopsies indicated that most of the
human melanoma tumour exudates tested contained very high MSH concentrations (>
500 pg/ml; 14/15), while plasma levels were generally normal (< or = 25 pg/ml;
10/15). The level in an exudate from a non-melanoma tumour type was < 40 pg/ml.
In vitro studies showed that release of the IR-alpha-MSH was time- and
temperature-dependent, and related to cell death.
PMID- 9640236
TI - Why are patients with malignant lymphomas excluded from clinical trials? The
experience of an oncology institute in Italy.
PMID- 9640237
TI - Human transplacental passage of the retinoid fenretinide (4HPR)
PMID- 9640238
TI - Comments on: Haemostatic abnormalities in lung cancer: prognostic implications,
Buccheri et al., Eur J Cancer, 33, pp. 50-55, 1997.
PMID- 9640239
TI - Inhibition of an established allergic response to ovalbumin in BALB/c mice by
killed Mycobacterium vaccae.
AB - Allergic disorders are mediated by T lymphocytes secreting T helper 2 (Th2)
cytokines, interleukin-4 (IL-4) and interleukin-5 (IL-5), resulting in high
levels of serum immunoglobulin E (IgE) and recruitment of eosinophils. One of the
treatment strategies is to downregulate the Th2 component by inducing a T helper
1 (Th1) response to the relevant allergen, because Th1 and Th2 cytokines are
thought to be mutually antagonistic. In this study, we examined the effects of
Mycobacterium vaccae, a potent inducer of Th1 immunity, on allergic responses in
a murine model. A single injection of M. vaccae into ovalbumin (OVA)-preimmunized
BALB/c mice suppressed serum IgE over a wide dose range (10(7), 10(8) or 10(9) M.
vaccae). Further experiments, using 10(7) M. vaccae injected twice, showed that
this treatment inhibited not only serum IgE, but also the potential for ovalbumin
induced IL-5 production by spleen cells. This non-specific ability of a
mycobacterium to decrease Th2 activity, even when not presented together with the
allergen, is in agreement with recent epidemiological studies on the impact of
bacillus Calmette-Guerin (BCG) vaccination, and of other potent Th1 stimuli, on
the incidence of atopy. The suppression of serum IgE and allergen-specific IL-5
synthesis by M. vaccae suggest that this organism is likely to have clinical
application in the immunotherapy of allergy.
PMID- 9640240
TI - Recognition of a common mycobacterial T-cell epitope in MPB59 of Mycobacterium
bovis.
AB - Bovine tuberculosis, which persists as a residual level of infection in many
European countries, has implications not only for the economy of farming
communities but also for human health. The aim of this study was to identify a
common mycobacterial antigen which was recognized in bovine tuberculosis and to
characterize the response to this antigen at the epitope level. A T-cell clone,
phenotype CD4+, raised from an animal experimentally infected with Mycobacterium
bovis was shown to proliferate in response to a panel of sonicates derived from
different mycobacterial species indicating recognition of an antigen with broad
specificity. This antigen was subsequently shown to be MPB59. Recognition of
MPB59 at the epitope level was determined in experimental and field cases of
bovine tuberculosis using a panel of synthetic peptides (20-mers with 10-residue
overlaps) incorporating the signal sequence and mature protein. The results
showed that in vitro interferon-gamma was predominantly produced in response to
adjacent peptides numbers 10 and 11, suggesting that the dominant epitope was
contained in the overlap, correlating to residues 101-110 (YYQSGLSIVM). This
epitope was recognized by 54% of tuberculous cattle of mixed breeds, which
suggests that it may be genetically permissive in terms of major
histocompatibility complex presentation. Sequence analysis confirmed that there
were only minor differences in the amino acid composition within this region for
various mycobacterial species, which could explain the common T-cell recognition
described in this study. Common recognition of this epitope indicates that it
would have limited potential for use as a diagnostic reagent per se but may have
potential for inclusion in a subunit vaccine.
PMID- 9640241
TI - In vivo exposure to Porphyromonas gingivalis up-regulates nitric oxide but
suppresses tumour necrosis factor-alpha production by cultured macrophages.
AB - The present study was designed to test whether the functional response of mouse
macrophages elicited by chronic exposure to bacteria will be different from that
of cells elicited by a non-bacterial irritant. Macrophage elicitation was
conducted by Porphyromonas gingivalis, a major periodontal pathogen, in
comparison to a standard elicitation by thioglycollate (TG). We measured
lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumour necrosis factor
alpha (TNF-alpha) secretion by the elicited macrophages, and the expression of
inflammatory cytokines in the whole elicited cell population. In addition, we
tested the response of TG-elicited macrophages to pretreatment with P. gingivalis
LPS in vitro. Mouse peritoneal macrophages were harvested 4 days after
intraperitoneal injection of TG or heat-killed P. gingivalis. TG-elicited
macrophages produced undetectable levels of TNF-alpha and approximately 0.5
microM of NO. The stimulation of the macrophages with LPS resulted in the
secretion of NO and TNF-alpha in a dose-dependent manner. The P. gingivalis
elicited macrophages produced basal levels of approximately 5 microM NO, but TNF
alpha was not detectable. LPS stimulation of these cells further increased the
secretion of NO eightfold while TNF-alpha remained undetectable. The NO secretion
by P. gingivalis-elicited cells was significantly higher than that by TG-elicited
cells. Examination of cytokine expression in the whole elicited cell population
revealed that both P. gingivalis-elicited cells and TG-elicited cells expressed
messenger RNA for interleukin-2 (IL-2), TNF-alpha and interferon-gamma (IFN
gamma), but not for IL-4. IL-6 was expressed in P. gingivalis-elicited cells
only. Pretreatment of TG-elicited macrophages with P. gingivalis LPS for 24 hr
prior to a second LPS challenge resulted in down-regulation of TNF-alpha
secretion and up-regulation of NO secretion, a response similar to that seen in
P. gingivalis-elicited peritoneal macrophages. The results suggest that the in
vivo exposure of resident macrophages to P. gingivalis induces functional changes
in peritoneal macrophages. These changes might be due to the effect of P.
gingivalis LPS.
PMID- 9640242
TI - In situ study on the pathogenesis and immune reaction of equine herpesvirus type
1 (EHV-1) infections in mice.
AB - The mouse model was used to study the pathogenesis of equine herpesvirus type 1
(EHV-1) after primary and secondary intranasal infections. Within a few hours
after infection, EHV-1 was found in nasal and olfactorial epithelium and sub
epithelial cells of the respiratory mucosa, but antigen-specific immune cells
were never detected. Next to the lung, EHV-1 was transmitted early and directly
to the brain, both via the olfactory route and the trigeminal nerve, but traces
of degenerative or inflammatory processes were not detected there. In the lung,
the immune cells residing or invading the parenchyma did not contain viral DNA or
proteins. The primary immune response in the lungs was an alveolar and
interstitial inflammation, dominated by the sequential appearance of neutrophils
and macrophages, while the number of T and B lymphocytes remained unaltered.
Within 24 hr after re-infection, lymphocytes accumulated around the blood
vessels, outnumbering monocytes more than twofold, without neutrophils appearing.
The lymphocytes comprised of little more B than T cells and the T cells were
predominantly CD8+ cells. Those and B cells infiltrated the parenchyma. These
results show the route of virus distribution and demonstrate the lack of antigen
specific immune cells in the lungs of mice after primary intranasal infection
with EHV-1.
PMID- 9640243
TI - The orf virus OV20.0L gene product is involved in interferon resistance and
inhibits an interferon-inducible, double-stranded RNA-dependent kinase.
AB - The parapoxvirus orf virus was resistant to type 1 (IFN-alpha) and type 2 (IFN
gamma) interferons in cultures of ovine cells. The recently identified orf virus
OV20.0L gene exhibits 31% predicted amino acid identity to the vaccinia virus E3L
interferon-resistance gene, and is referred to as the (putative) orf virus
interferon-resistance gene (OVIFNR). The objective of this study was to determine
whether OVIFNR was involved in interferon resistance. Recombinant OVIFNR as a
thioredoxin fusion protein (OVIFNR-Tx) inhibited the activation (by
autophosphorylation) of an interferon-inducible, double-stranded (ds) RNA
dependent kinase (PKR) of sheep, which was shown to bind dsRNA (poly I:C). PKR in
other species is involved in the inhibition of protein synthesis as part of the
antiviral state in infected cells. Virus-infected cell lysates, but not control
lysates, from cells grown in the presence of cytosine arabinoside also contained
PKR inhibitory activity, which indicated that the inhibitory activity was
associated with early viral gene expression. Significantly, the OVIFNR gene
expressed in interferon-treated ovine fibroblasts protected the unrelated Semliki
Forest virus from the antiviral effect of both type 1 and type 2 interferons.
Taken together, the results indicate that the OVIFNR gene functions as an
interferon-resistance gene, the product of which inhibits PKR in a similar way to
the vaccinia virus E3L gene product.
PMID- 9640244
TI - The CD4+ T-cell response to protein immunization is independent of accompanying
IFN-gamma-producing CD8+ T cells.
AB - By virtue of their strong bias towards production of interferon-gamma (IFN
gamma), CD8+ T cells have the potential to promote the development of type 1
immune responses. We have previously shown that the CD4+ T-cell response to
immunization with the protein antigen keyhole limpet haemocyanin (KLH) has a
mixed interleukin-4 (IL-4)/IFN-gamma production profile. Here we show that this
immunization regimen also stimulates accumulation in the draining lymph nodes of
CD8+ T cells, which preferentially contain IFN-gamma mRNA ex vivo and secrete IFN
gamma protein in vitro. This provides a model to test whether CD8+ cell-derived
IFN-gamma participates in the normal control of the immune response to a non
viable exogenous antigen. To investigate regulation of the anti-KLH response by
the CD8+ population or IFN-gamma produced by this or other cell types, mice were
administered depleting antibodies. Depletion of CD8+ cells had no effect on the
frequency of clonogenic KLH-specific CD4+ T cells, the IL-4/IFN-gamma profiles of
their progeny, or the isotype profiles of the serum antibody response to KLH. In
contrast, IFN-gamma neutralization diminished cell accumulation in the lymph
nodes and reduced both the frequency of KLH-specific CD4+ T cells that gave rise
to IFN-gamma-producing clones and serum titres of KLH-specific IgG2a and IgG3.
Therefore, despite the potential for cross-regulation, the CD4+ T-cell response
to this immunogen is independent of the IFN-gamma-skewed CD8+ response.
PMID- 9640245
TI - Kinetics of cytokine and NFAT gene expression in human interleukin-2-dependent T
lymphoblasts stimulated via T-cell receptor.
AB - T cells respond to mitogenic or antigenic stimulation by proliferation and by
turning on cytokine gene expression. Here we have analysed the kinetics and
nature of cytokine production in human peripheral blood-derived T lymphoblasts
stimulated with anti-CD3 antibodies or Lens culinaris lectin (LCL). T cells were
purified from peripheral blood mononuclear cells (PBMC) and primarily activated
with anti-CD3 antibodies and cultured in the presence of interleukin-2 (IL-2).
Anti-CD3-restimulated T cells (mainly CD8+) produced IL-2, interferon-gamma (IFN
gamma) and tumour necrosis factor-alpha (TNF-alpha) and low levels of IL-4 and IL
10 transcripts and proteins. No IL-6 gene expression was observed. In LCL
stimulated cells the cytokine production pattern was very similar. Steady-state
mRNA levels of IL-2, IL-10 and IFN-gamma peaked at 3 hr after anti-CD3
stimulation and declined rapidly thereafter. The kinetics of TNF-alpha mRNA
expression was faster, being at its peak level 1 hr after stimulation. Anti-CD3
stimulated IL-2 gene expression was down-regulated by protein synthesis
inhibitor, whereas IL-10, IFN-gamma and TNF-alpha genes were readily induced
independent of ongoing protein synthesis. T-cell receptor stimulation also
induced a very rapid expression of c-jun, c-fos and NFATc1 (NFATc) genes, the
gene products of which are involved in cytokine gene expression. In conclusion,
the cytokines synthesized by IL-2-dependent T cells were predominantly IL-2, IFN
gamma and TNF-alpha.
PMID- 9640246
TI - Simultaneous cross-linking of CD6 and CD28 induces cell proliferation in resting
T cells.
AB - In the present study, we showed that simultaneous ligation of the monoclonal
antibodies (mAb) against CD6 and CD28 induces T-cell proliferation in purified
resting T lymphocytes in the absence of T-cell receptor (TCR) occupancy. No cell
proliferation was observed when the mAb were cross-linked alone or used
simultaneously in the soluble form. T-cell proliferation mediated through
CD6/CD28 is accompanied by the up-regulation of interleukin-2 (IL-2) mRNA and
expression of IL-2 receptors on the cell surface. In the presence of IL-2
neutralizing mAb the proliferative response of the T cell induced through
CD6/CD28 was inhibited dose dependently. Cross-linking mAb to CD6 and CD28 alone
or together did not down-regulate the CD3/TCR complex. T-cell proliferation
mediated through CD6/CD28 was only partially blocked by the immunosuppressive
drug, cyclosporin A (CsA), whereas anti-CD28-induced T-cell proliferation in the
presence of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was
unaffected. In sharp contrast T-cell proliferation mediated by anti-CD6 in the
presence of TPA was efficiently blocked by CsA. In addition, two protein kinase C
(PKC) inhibitors, GF 109203X and H-7 dose-dependently inhibited T-cell
proliferation mediated through CD6/CD28, suggesting that PKC activation may be
involved. Furthermore, there was a marked differential dose-dependent inhibitory
effect of the PKC inhibitors on T-cell proliferation mediated by the co-ligation
of anti-CD6 or anti-CD28 in the presence of anti-CD3, with the former being more
sensitive to PKC inhibition. Taken collectively, our results suggest that T-cell
activation can occur through an antigen-independent pathway by cross-linking the
accessory molecules, CD6 and CD28, and that these two cell surface antigens may
have distinct signalling pathways.
PMID- 9640247
TI - Non-responsiveness of antigen-experienced CD4 T cells reflects more stringent co
stimulatory requirements.
AB - We recently reported that previously activated T cells, irrespective of the
nature of the first stimulus they encountered, are unable to respond to
Staphylococcal enterotoxin B (SEB), nor to soluble anti-CD3 monoclonal antibody
(mAb) presented by splenic antigen-presenting cells (APC). Such previously
activated T cells are, however, fully capable of responding to plate-bound anti
CD3 plus splenic APC. These data suggest differential integration of the T-cell
receptor (TCR) and co-stimulatory signalling pathways in naive versus antigen
experienced T cells. Consistent with this hypothesis, anti-CD28 mAb restores the
proliferative capacity of resting ex vivo CD45RBlo CD4+ T cells (representing
previously activated T cells) to both soluble anti-CD3 mAb and SEB.
Interestingly, mAb-mediated engagement of cytotoxic T-lymphocyte antigen-4 (CTLA
4) completely negates the rescue effects mediated by anti-CD28 mAb in CD45RBlo
cells. Nevertheless, the non-responsiveness of CD45RBlo CD4+ T cells cannot be
reversed by anti-CTLA-4 Fab fragments, indicating that it is not related to
negative regulatory effects of CTLA-4 engagement itself. Interestingly, the
addition of interleukin-2 (IL-2) restores the proliferative capacity of CD45RBlo
CD4+ T cells to SEB and soluble anti-CD3 mAb. Moreover, when rescued by IL-2, the
cells are less susceptible to the negative regulatory effects of CTLA-4
engagement. Together, these findings suggest that the non-responsiveness of
CD45RBlo CD4+ T cells to certain stimuli may be related to inadequate TCR
signalling, primarily affecting IL-2 production.
PMID- 9640248
TI - The transmembrane region of CD2-associated signal-transducing proteins is crucial
for the outcome of CD2-mediated T-cell activation.
AB - Signalling through the CD2 molecule was shown previously to employ similar
signalling molecules as the T-cell receptor (TCR). Here, we show that CD2
mediated signalling is strongly influenced by the expressed transmembrane region
of the employed signal-transducing molecule. We used TCR-negative cells
expressing chimeric fusion proteins that consist of human interleukin-2 (IL-2)
receptor alpha-chain-derived sequences (hCD25) fused to mouse-specific zeta-chain
segments (hCD25-zeta). One set of TCR-negative cell lines expressed the hCD25
derived extracellular part fused to mouse-specific transmembrane and cytoplasmic
zeta-protein sequences ('TZZ'). The second type of cell lines expressed the hCD25
derived extracellular and transmembrane portions fused to the mouse-specific zeta
chain cytoplasmic segment ('TTZ'). After cross-linking the hCD25-zeta molecules
with specific monoclonal antibodies (mAb), all TCR-negative cell lines produced
similar amounts of IL-2. Cross-linking with stimulating pairs of CD2-specific
mAb, however, led to IL-2 production only in cell lines expressing the zeta-chain
specific transmembrane segment. Co-cross-linking of CD25 and CD2 molecules
resulted in an effective stimulation of both TZZ- and TTZ-expressing cell lines.
Moreover, TTZ- and TZZ-expressing cell lines differed in their pattern of
tyrosine-phosphorylated proteins after stimulation with hCD25-specific mAb. Thus,
although CD2 and TCR molecules share signalling components and pathways, the fine
tuning of CD2 co-receptor function appears to be regulated in part by
transmembrane regions of signal-transducing molecules like the TCR-associated
zeta-chain.
PMID- 9640249
TI - The CD8+ granzyme B+ T-cell subset in peripheral blood from healthy individuals
contains activated and apoptosis-prone cells.
AB - Granzyme B (GrB) has been implicated in induction of apoptosis in target cells.
The presence of GrB in peripheral blood CD8+ T cells from healthy individuals was
analysed in immunocytochemical and flow cytometric studies. Furthermore, CD8+ GrB
T cells and CD8+ GrB+ T cells were compared regarding phenotypical
characteristics and susceptibility to both spontaneous and Fasmediated apoptosis.
GrB was expressed by approximately one-fifth of CD8+ T cells. Compared with the
CD8+ GrB- T-cell subset, the CD8+ GrB+ T-cell subset contained cells that were
relatively more activated and more prone to spontaneous apoptosis. Culturing of
cells with immunoglobulin M (IgM) anti-Fas monoclonal antibody had no additional
effect on the number of CD8+ GrB+ T cells undergoing apoptosis. We suggest that
the presence of CD8+ GrB+ T cells in peripheral blood from healthy individuals
results from immune surveillance or contact with infectious agents, and that
spontaneous apoptosis of these cells might serve as a mechanism for their
eventual clearance.
PMID- 9640250
TI - Gene transfer of costimulatory molecules into a human colorectal cancer cell
line: requirement of CD54, CD80 and class II MHC expression for enhanced
immunogenicity.
AB - Colorectal cancer is considered a non-immunogenic malignany. One strategy to
augment the immunogenicity of such tumours is represented by the expression of
costimulatory molecules by gene transfer. Using transfected variants of the human
colorectal cancer cell line SW480 we tested various costimulatory molecules
(CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele
(HLA-DR3) alone or in combination on their ability to support primary T
lymphocyte activation in vitro. Expression of CD80 or CD86 similarly as the
combination of both was not sufficient to induce proliferation of human
allogeneic T cells. Expression of CD54 together with CD80 strongly augmented the
costimulatory function of CD80, as observed in the presence of a CD3 monoclonal
antibody (mAb), but did not lead directly to a T-cell response against modified
tumour cells. Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3
allele effectively promoted T-lymphocyte proliferation. Moreover, the use of such
CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the
generation of T-cell lines predominantly composed of CD8+ T cells exhibiting
class I MHC restricted cytolytic activity towards untransfected SW480 tumour
cells. This demonstrates that the generation of immunogenic tumour cell variants,
i.e. for the use as cellular vaccines, requires multiple genetic alterations in
the case of non-immunogenic human tumours cells, such as colorectal cancer cells.
PMID- 9640251
TI - Emigration of mature T cells from the thymus is inhibited by the imidazole-based
compound 2-acetyl-4-tetrahydroxybutylimidazole.
AB - The primary role of the thymus is to provide mature T cells for the peripheral
immune system. The mechanisms involved in the cellular export processes are as
yet unknown. In this study, we examined the ability of 2-acetyl-4
tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia
caramel food colouring, to inhibit T-cell export from the thymus. BALB/c mice
were maintained on drinking water containing THI for 5 days. The mice showed a
twofold increase in the total number of mature medullary thymocytes (CD4+CD8- and
CD4-CD8+) as well as a slight decrease in the total number of immature double
positive cells (CD4+CD8+). The mature single-positive thymocytes were found to
express high levels of the homing molecule L-selectin, suggesting that these
potential emigrants were prevented from leaving the thymus. To confirm this, THI
treated mice were injected intrathymically with fluorescein isothiocyanate and
the number of labelled T cells appearing in the lymph nodes and spleen was
determined 16 hr later. A 10-fold decrease in the number of CD4+ and CD8+ recent
thymic emigrants in the lymph nodes and spleen of THI-treated mice was observed.
Previous studies have shown that THI does not affect other aspects of thymocyte
development, such as proliferation and differentiation. Taken together, these
results suggest that the immunosuppressive effects of THI may be due, in part, to
preventing of the final step of T-cell export out of the thymus.
PMID- 9640252
TI - CD4+ T cells, but not CD8+ T cells, are required for the development of
experimental autoimmune gastritis.
AB - Murine autoimmune gastritis, induced by neonatal thymectomy, is characterized by
a mononuclear infiltrate within the gastric mucosa, loss of parietal and
zymogenic cells and circulating autoantibodies to the gastric H/K ATPase. The
infiltrate contains both CD4+ and CD8+ T cells. Here we have investigated the
roles of CD4+ and CD8+ T cells in the development of gastritis by in vivo
treatment with depleting rat anti-CD4 and anti-CD8 monoclonal antibodies.
Depletion of CD4+ T cells decreased the incidence of gastric mononuclear
infiltrates from 63% (5/8), observed in normal rat immunoglobulin G (IgG)
injected mice, to 8% (1/12) and also abolished the production of antigastric
autoantibodies. In contrast, depletion of CD8+ T cells did not reduce the
incidence of gastritis. The absence of CD8+ T cells in the infiltrate of the
stomach of anti-CD8(+)-treated mice was confirmed by immunocytochemistry. These
results argue that neonatal thymectomy-induced autoimmune gastritis is mediated
by CD4+ T cells and that CD8+ T cells do not play a significant role in the
development of the gastric lesion.
PMID- 9640253
TI - An increase in basal glucocorticoid concentration with age induces suppressor
macrophages with high-density Fc gamma RII/III.
AB - Ageing is usually accompanied by a decline in immune and neuroendocrine
functions. To elucidate the mechanisms underlying age-related immunosuppression,
the functions and surface phenotypes of peritoneal cells in the
monocyte/macrophage lineage from old mice were investigated. The role of
glucocorticoids (GC) in the immunomodulation was also examined. Proliferative
responses of spleen cells from control mice stimulated with concanavalin A (Con
A) were significantly suppressed by adding peritoneal exudate cells from old
mice. Flow cytometry analysis revealed that the proportion of MAC-1+ cells with a
high density of type II or type III receptor for the Fc portion of IgG (Fc gamma
RII/IIIbright cells) was increased markedly in the periotoneal exudate cells from
old mice. The prominent suppressor activity for Con A responses of control spleen
cells was found in the Fc gamma RII/IIIbright cells, whereas MAC-1+ cells with a
low density of Fc gamma RII/III (Fc gamma RII/IIIdull cells) did not suppress the
Con A responses. On the other hand, both the basal corticosterone concentrations
in serum and the mRNA expression for GC receptor in peritoneal exudate cells
increased significantly in old mice. Furthermore, the proportion of Fc gamma
RII/IIIbright cells in peritoneal exudate cells from old mice was normalized on
administration of the GC antagonist RU 38,486 (mifepristone). These results
suggest that the increase in basal corticosterone concentrations in old mice
induces the generation of Fc gamma RII/IIIbright suppressor cells, possibly
leading to the immune-suppressive state.
PMID- 9640254
TI - Lysis-sensitive targets stimulate an elevation of cAMP in human natural killer
cells.
AB - Natural killer (NK) cells are lymphocytes that are capable of destroying tumour
cells and virally infected cells (cytolysis) without prior sensitization. When
cAMP is artificially elevated in NK cells, it is a potent inhibitor of their
cytolytic function. We investigated whether NK-cell cAMP levels are modulated in
response to tumour target cells to determine the potential of cAMP as a
physiological regulator of NK cytotoxic function. When NK cells are exposed to a
range of lysis-sensitive (LS) tumour-target cells there is an increase in
intracellular cAMP levels in the NK cells over a 60-min period. The peak increase
in cAMP (200-400% above control) occurs at 30 min for all LS targets tested.
There is no increase in NK-cell cAMP in response to lysis-resistant (LR) tumour
target cells. The cAMP elevation may be dependent on both LS-target-stimulated
adenylyl cyclase (AC) activation and LS-target-stimulated phosphodiesterase (PDE)
inhibition. When the NK cells are pretreated with the protein tyrosine kinase
(PTK) inhibitor, genistein (30 micrograms/ml), the AC-activation component of the
cAMP elevation is abolished. Thus, the AC-activation component appears to require
PTK activation. When NK cells are pretreated with the protein kinase C (PKC)
inhibitor, chelerythrine chloride (10 microM) the cAMP elevation in response to
LS targets was not diminished. This indicates that neither the AC-activation
component nor any PDE-inhibition component require PKC activation.
PMID- 9640255
TI - Cloning and sequencing of a cDNA encoding chicken mannan-binding lectin (MBL) and
comparison with mammalian analogues.
AB - The serum lectin, mannan-binding lectin (MBL) (also denoted mannan-binding
protein or mannose-binding protein, MBP) has been identified in mammals (humans,
monkey, cow, rabbit, mouse and rat). Upon binding to carbohydrates on the surface
of microorganisms, MBL mediates activation of the complement system, leading to
killing of the microorganism. MBL thus exerts a role in the innate immune
defence. We have described the isolation and partial characterization of an
analogous protein in chicken serum. Oligonucleotides based on the N-terminal
sequence of this protein were used in a reverse transcription-polymerase chain
reaction (RT-PCR) with chicken liver RNA as template. The PCR product was
sequenced and found to encode part of the NH2 terminus of chicken MBL. A perfect
match probe was synthesized and used to screen a chicken liver cDNA library. The
isolated clones carried a cDNA insert of 1692 bp with an open reading frame of
714 bp encoding a mature protein of 238 amino acids including a signal peptide of
five amino acids. The deduced amino acid sequence agrees with those determined by
conventional amino acid sequence analysis of the peptides except for four
residues. We have compared the deduced primary structure of chicken MBL with the
mammalian analogues. The phylogenetic analysis indicates that the gene
duplication leading to two different MBL forms in mammals occurred after the
split from birds and reptiles. This concurs with the finding of only one form of
MBL in chickens.
PMID- 9640256
TI - The plasma levels of coglutinin are heritable in cattle and low levels predispose
to infection.
AB - Conglutinin, like mannan-binding lectin (MBL) and CL-43, is a serum collection
involved in the innate immune defence system. In man, low serum MBL
concentrations, resulting from mutations in the collagen region, are associated
with a common opsonic defect. Plasma levels of conglutinin in cattle were assayed
by rocket immunoelectrophoresis to examine whether they were genetically
determined. Samples were collected from calves (309 bull-calves and 260 heifers
with complex pedigree relationships). The number of respiratory infections from
the 42nd to 336th day of life was recorded. The number of infections was found to
be genetically determined (heritability: h2 = 0.31 +/- 0.07). A wide
concentration range of conglutinin was found in plasma (< 1.25-35 micrograms/ml
for females, geometric mean 8.1 micrograms/ml, and < 1.25-47 micrograms/ml for
males, geometric mean 15.5 micrograms/ml), and the concentrations was found to be
genetically determined (heritability, h2 = 0.52 +/- 0.07). The analysis revealed
a negative association between disease frequency and the conglutinin levels (
0.56 +/- 0.18 for female; -0.50 +/- 0.18 for male). Levels of conglutinin below
the detection limit of the assay (1.25 micrograms/ml) were found in 2% of the
animals. If these animals are assumed to be homozygous for a single recessive
allele causing low concentrations a gene frequency of 0.15 could be calculated.
These findings suggests that selection for resistance against infectious disease
is possible in cattle and that the level of plasma conglutinin may be a helpful
trait in such a breeding scheme.
PMID- 9640257
TI - Calreticulin associates with non-HLA-A,-B class I proteins in the human
choriocarcinoma cell lines JEG-3 and BeWo.
AB - Human placental trophoblast expresses as unusual repertoire of major
histocompatibility complex (MHC) class I products that appears to reflect the
unique role of this epithelium in mediating feto-maternal relations during
pregnancy. Trophoblast is devoid of human leucocyte antigen (HLA)-A,-B antigens
but can express one or more non-HLA-A,-B class I proteins. The human
choriocarcinoma cell lines JEG-3, BeWo and JAR are widely used as models to study
trophoblast. During attempts to isolate non-HLA-A,-B class I from JEG-3 and BeWo
by immunoaffinity chromatography using a monoclonal antibody to beta 2
microglobulin we observed a 55,000 MW protein co-purifying with class I. N
terminal amino acid sequencing and immunoblotting using a specific antiserum
identified this product as calreticulin, a molecule recently shown to be involved
in the assembly of classical class I in human B-lymphoblastoid cells. In our
hands JEG-3 and BeWo were found to express 45,000 MW non-HLA-A,-B class I
proteins while the 40,000 MW HLA-G product was identified only in JEG-3. Our data
suggest that calreticulin associates with non-HLA-A,-B class I heterodimers and
with free 45,000 MW non-HLA-A,-B class I H chains in JEG-3. JAR was found to be
devoid of detectable class I H chains but contained beta 2-microglobulin and
calreticulin. However, calreticulin-beta 2-microglobulin complexes were not
detected in JAR. Calreticulin and class I were apparently co-localized within the
endoplasmic reticulum of JEG-3 cells whereas only class I was expressed at the
cell surface. These studies demonstrate that calreticulin is associated with non
HLA-A,-B class I products in human choriocarcinoma cells.
PMID- 9640258
TI - Effect of testosterone and cortisol administration on the reproductive tract of
male Antechinus stuartii (Marsupialia).
AB - The life history of Antechinus stuartii, a marsupial, is highly synchronized and
culminates in a brief mating period that is followed by complete male mortality.
The accessory reproductive tracts of male A. stuartii enlarge in association with
testosterone and cortisol hormone concentrations, but this appears to be
unrelated to the spermatogenic cycle. The present study examined the effects of
testosterone and cortisol on the male reproductive tract. Four groups of adult
males from May (when plasma testosterone and cortisol concentrations are low)
were given depot injections of testosterone esters or synthetic cortisol in doses
that mimic concentrations found in males in the breeding period (August). Males
were given either saline, testosterone only, cortisol only, or testosterone plus
cortisol. Experimental groups did not differ in the seminiferous tubule
morphology. However, the cells from the caudal end of the epididymides of both
testosterone groups were considerably hypertrophied compared with males treated
with saline or cortisol only. Testosterone treatment significantly increased
prostate and bulbourethral gland mass, although addition of cortisol to the
testosterone administration diminished this effect. The morphology of the
accessory reproductive tract of males treated with either saline or cortisol only
was similar to that of untreated males at the same time of year, and the
morphology of the accessory reproductive tract of males treated with testosterone
plus cortisol was similar to that of untreated males in the breeding season. Like
some other marsupials, the spermatogenic cycle in A. stuartii is apparently not
correlated with androgen activity, while the accessory reproductive tract is
affected by androgens.
PMID- 9640259
TI - Role of nitric oxide and cyclooxygenase products in controlling vascular tone in
uterine microvessels of rats.
AB - The importance of nitric oxide (NO) and dilator prostaglandins in uterine
resistance arterioles was investigated. In pentobarbital anaesthetized rats at
dioestrus-2, the uterine microcirculation in vivo was transilluminated by a
fibreoptic probe and microvessels (circumferential arterioles) viewed by video
microscopy. Arteriolar diameters were measured while increasing concentrations of
acetylcholine (ACh), serotonin (5-HT), phenylephrine (PE), or angiotensin II
(AII) were applied topically (suffused) over the uterus. Agonists were applied
alone or with ibuprofen (IBU; cyclooxygenase inhibitor), N omega-nitro-L-arginine
(L-NA; nitric oxide synthase inhibitor) or both. Circumferential arterioles were
dilated by ACh and 5-HT (10(-8)-10(-4) mol l-1) and constricted by PE (10(-8)-10(
5) mol l-1) and AII (10(-11)-10(-7) mol l-1). Suffusion of L-NA or L-NA with
ibuprofen (10(-4) mol l-1 each) abolished ACh-induced dilation; ibuprofen alone
blocked dilation at higher ACh concentrations. Serotonin-induced relaxation was
significantly attenuated by L-NA alone or in combination with ibuprofen.
Vasoconstriction induced by PE was enhanced by L-NA alone and L-NA with
ibuprofen, but ibuprofen alone had no effect. In contrast, AII-induced
constriction was enhanced significantly by ibuprofen or L-NA and further enhanced
when both ibuprofen and L-NA were present. These results suggest that ACh can
release either nitric oxide (NO) or cyclooxygenase products to cause uterine
arteriolar dilation and that 5-HT-induced uterine microvascular relaxation is
mediated via NO only. They also suggest that PE-induced vasoconstriction is
attenuated by the release of NO but not cyclooxygenase products and that
constrictor responses evoked by AII are attenuated by both NO and dilator
prostaglandin release. Thus, both nitric oxide and dilator prostaglandins are
important in the control of uterine microvessels.
PMID- 9640260
TI - Diet-induced loss of cyclic ovarian function at normal body weight in a rodent
model for bulimia nervosa.
AB - A bulimic rat model was used to test whether type and frequency of food intake
mimicking that in human bulimia nervosa could disrupt oestrous cyclicity, induce
an effect on glycoprotein (LH) structure, or affect both processes and if so, to
determine whether any such effects were acute, or persisted after return to
normal eating patterns. Voluntary hyperphagia was induced by offering female rats
a varied and palatable choice of human food items--the 'cafeteria diet'. There
were four groups: control (normal chow), obese (continuous cafeteria diet), post
obese (cafeteria diet, then fasted to reduce weight to that of controls) and
binge (cafeteria alternated with normal diet every few days). Animals were
maintained on these diets for 60 days (phase I). They were then given a GnRH
challenge on day 2 of dioestrus of the cycle. Twenty-four hours later, half of
the animals in each group were killed for assessment of effects on their
reproductive organs. The remaining animals were returned to normal diets and kept
for a further 40 days, when the GnRH challenge was repeated and the animals were
killed 24 h later (phase II). All animals on the cafeteria diet in phase I
exhibited significant disruption of oestrous cyclicity irrespective of body
weight. LH released in response to the first GnRH challenge showed a prolonged
half-life, and/or increased rate of secretion in the obese and post-obese groups
but in the binge group the secretory/clearance properties resembled those of
control animals. After the second GnRH challenge at the end of phase II, however,
the LH of the binge group appeared to have different secretory or clearance
characteristics, whereas that of the previously obese animals had returned to
normal. These data show ovarian cyclicity was disrupted by hyperphagia and
irregular eating, even at normal body weight. Relating ovarian function to
pituitary output in terms of LH, the effects of the continuous cafeteria diet did
not appear to persist in the animals that returned to normal diets, but in the
binge group the effect, presumably of the diet manipulation, was manifested after
return to a normal eating pattern. This finding suggests that irregular eating
habits may exert a direct (and acute) effect on the ovary, but that effects on
the pituitary (and LH glycoforms) take longer to be expressed, explaining many
features of bulimia nervosa.
PMID- 9640261
TI - Oxytocin- and aluminium fluoride-induced phospholipase C activity and
prostaglandin F2 alpha secretion during the ovine luteolytic period.
AB - A series of studies was conducted to characterize changes in components of the
cell signalling cascade that mediates oxytocin-induced prostaglandin F2 alpha
(PGF2 alpha) synthesis at the onset of luteolysis in sheep. In the first
experiment, caruncular tissue was dissected from 20 ewes on days 12-15 of the
oestrous cycle, and incubated for the measurement of phospholipase C (PLC)
activity or secretion of PGF2 alpha. Activation of GTP-binding proteins with
aluminium fluoride stimulated both inositol phosphate accumulation and PGF2 alpha
secretion on all days examined. However, oxytocin did not stimulate PLC activity
or PGF2 alpha accumulation until day 13. While the ability of oxytocin to
stimulate PLC activity increased after day 13, oxytocin-induced PGF2 alpha
secretion declined slightly from day 13 to 15, suggesting that cell signalling
components downstream from PLC modulate the response to oxytocin after day 13.
Oxytocin failed to stimulate PGF2 alpha synthesis on day 14 after oestrus.
Secretion of endogenous luteal oxytocin may have rendered uterine tissues
collected on day 14 refractory to oxytocin in vitro. Therefore, a second study
was conducted in ovariectomized, steroid replaced ewes. Ovarian steroids were
administered to mimic endogenous changes in progesterone and oestradiol. The
temporal patterns of PGF2 alpha synthesis in response to oxytocin and
pharmacological agents were similar to uterine tissues from cyclic ewes in the
first experiment; however, the magnitude of the response was less. These data
suggest that oxytocin receptors are absent or are not coupled to PLC until day 13
after oestrus.
PMID- 9640262
TI - Localization of follistatin in the rat testis.
AB - The cellular localization of the activin-binding protein, follistatin, in the rat
testis has been a matter of some controversy with different investigators
claiming that Sertoli cells, Leydig cells or germ cells are the primary cell
types containing this protein. The localization of mRNA encoding follistatin was
re-examined using reverse transcription-polymerase chain reaction (RT-PCR) and in
situ hybridization as well as the distribution of follistatin by
immunohistochemistry. The results demonstrate that mRNA encoding follistatin is
located in many germ cells including type B spermatogonia, primary spermatocytes
with the exception of the late leptotene and early zygotene stages, and
spermatids at steps 1 to 11. It is also found in Sertoli cells and endothelial
cells but not in Leydig cells. Immunohistochemistry, using two different antisera
to follistatin, showed that this protein was localized to spermatogonia, primary
spermatocytes at all stages except the zygotene stage, spermatids at all stages
and to endothelial cells and Leydig cells in the intratubular regions. The
failure to detect mRNA for follistatin in Leydig cells using RT-PCR and in situ
hybridization suggests that the immunohistochemical localization in these cells
reflects binding of follistatin produced elsewhere. The widespread localization
of follistatin, taken together with its capacity to neutralize the actions of
activin, may indicate that follistatin modulates a range of testicular actions of
activin, many of which remain unknown.
PMID- 9640263
TI - Depletion of vitamin C from pig corpora lutea by prostaglandin F2 alpha-induced
secretion of the vitamin.
AB - The luteolytic effects of prostaglandin F2 alpha (PGF2 alpha) are thought to be
mediated in part by the promotion of an increasingly oxidative cellular
environment. Loss of antioxidants is one mechanism by which PGF2 alpha might
induce or exacerbate oxidative damage within the corpus luteum. This study was
performed to establish whether depletion of vitamin C is an acute effect of PGF2
alpha on the pig corpus luteum and to gain insight into the mechanism of luteal
vitamin C loss at luteolysis. Gilts (n = 4) were anaesthetized and both utero
ovarian veins and an ear vein were catheterized. Each corpus luteum on the
treated ovary received an intraluteal injection of PGF2 alpha (1 microgram)
followed by a sustained release implant containing 100 micrograms of the
prostaglandin. The other ovary served as the control and each corpus luteum
received corresponding volumes of injection vehicle and blank implant. Blood was
collected from the ear vein and both utero-ovarian veins every 15 min beginning
15 min before the onset of treatment. Collection of blood stopped when animals
were ovariectomized and corpora lutea were collected at 2 h after treatment.
Progesterone and vitamin C (ascorbate) concentrations were measured in tissue and
plasma samples. PGF2 alpha-treated luteal tissue had similar progesterone, but
significantly lower ascorbate, concentrations when compared with control corpora
lutea. PGF2 alpha treatment resulted in a rapid and sustained increase in plasma
ascorbate within the treatment-side utero-ovarian vein, while the control utero
ovarian vein and ear vein showed little change in plasma ascorbate during the
experimental period. No effect of PGF2 alpha on plasma progesterone was evident.
This finding suggests that PGF2 alpha depletes the pig corpus luteum of vitamin C
by inducing secretion of the vitamin into the bloodstream. Further studies are
necessary to determine whether the depletion of vitamin C that is induced by PGF2
alpha contributes to the demise of the pig corpus luteum.
PMID- 9640264
TI - Effect of acute treatment with progesterone on the timing and synchrony of
ovulation in Bos indicus heifers treated with a norgestomet implant for 17 days.
AB - The aim of the present study was to develop a treatment protocol for the precise
synchronization of oestrus that would avoid the development of persistent
dominant ovarian follicles. Bos indicus heifers, in which oestrous cycles had
been presynchronized, were allocated randomly, according to the day of their
oestrous cycle, to one of five treatment groups. All heifers received a
subcutaneous ear implant containing 3 mg of norgestomet for 17 days starting on
day 0 and an injection of an analogue of prostaglandin F2 alpha on days 0 and 4.
Heifers in group 1 (control group; n = 7) received no other treatment, while
heifers in groups 2 (n = 8), 3 (n = 7), 4 (n = 7), and 5 (n = 7) received a
single progesterone-releasing controlled internal drug release device (CIDR) for
24 h on days 10, 12, 14 and 16, respectively. Treatment with a single CIDR
delayed the mean time of ovulation and the day of emergence of the ovulatory
follicle in heifers treated on days 14 and 16 compared with control heifers (P <
0.05). There was less variation in the interval to ovulation in heifers treated
on day 10 compared with other treated heifers (P < 0.05). The variation among
heifers in the day of emergence of the ovulatory follicle and the age of the
ovulatory follicle at ovulation was less for all groups treated with a CIDR than
for the control group (P < 0.05). The duration of dominance and variation in the
duration of dominance of the ovulatory follicle was less in heifers treated with
a CIDR device on days 10 and 16 than for control heifers (P < 0.05). Mean age
(days from emergence to ovulation) of the ovulatory follicle did not differ among
treatment groups (P > 0.05). Concentrations of LH and oestradiol decreased
coincident with increased concentrations of progesterone on the days of CIDR
treatment in treated compared with control heifers (P < 0.02) but increased again
after removal of the CIDR. A smaller proportion of follicles in the growing phase
of follicular development at the time of CIDR treatment become atretic compared
with follicles that had reached a plateau phase of follicular growth (14.3% (1/7)
versus 90.5% (19/21), respectively; P < 0.001). It was concluded that acute
treatment with progesterone can influence the growth pattern of ovarian
follicular development. However, the effect varies with the stage of ovarian
follicular development. Short term treatment with progesterone 7 days before the
end of a 17 day period of norgestomet treatment resulted in precise synchrony of
ovulation without the ovulation of a persistent dominant ovarian follicle.
PMID- 9640265
TI - Anti-Mullerian hormone (AMH) secretion in prepubertal and adult rams.
AB - The aim of the present analysis was to determine whether anti-Mullerian hormone
concentrations in prepubertal plasma or adult rete testis fluid are related to
the number or function of Sertoli cells in rams or to the presence of the FecB
Booroola gene. Twenty rams from two Booroola crosses, differing in their
testicular masses were analysed; in each cross, half of the animals were
heterozygous carriers of the FecB gene. The data from rams, during prepuberty and
at adulthood during the non-sexual season, were analysed by two-way ANOVA and
residual correlations. In 4-week-old intact male lambs, the mean anti-Mullerian
hormone plasma concentration was 15 ng ml-1, irrespective of cross, genotype or
eCG stimulation; it was significantly negatively correlated with FSH (r = -0.51;
P = 0.02; n = 19). In adults, anti-Mullerian hormone was not detectable in plasma
and was 0.5 ng ml-1 in rete testis fluid, irrespective of cross or genotype. The
total number of Sertoli cells per testis was not related to anti-Mullerian
hormone concentration in lamb prepubertal plasma or in adult rete testis fluid.
The concentration of anti-Mullerian hormone in adult rete testis fluid was
significantly and negatively correlated with the daily production of leptotene
primary spermatocytes per testis (r = -0.56; P = 0.02; n = 16). The mean
oestrogen concentration in the adult testicular vein was 2 pg ml-1 and was
correlated negatively with the rete testis fluid concentration of anti-Mullerian
hormone (r = -0.60; P = 0.02; n = 15) and correlated positively with the daily
production of leptotene primary spermatocytes per testis (r = 0.53; P < 0.05; n =
19). In conclusion, anti-Mullerian hormone secretion was not correlated with the
total numbers of Sertoli cells per testis and cannot be used as a predictor of
the number of Sertoli cells. Anti-Mullerian hormone secretions were not affected
by the presence of FecB gene. However, anti-Mullerian hormone secretion could be
considered to be inversely related to the daily production of primary
spermatocytes by the testis.
PMID- 9640266
TI - Differential localization of laminin chains in bovine follicles.
AB - The composition of a basal lamina markedly affects its ability to filter material
and affects the fate of adjacent epithelial cells. Therefore, basal laminae
differ in composition with tissue development, and between different tissues in
the body. Laminins are a component of basal laminae and consist of one alpha, one
beta and one gamma chain, of which there are at least five, three and two
isoforms, respectively. This is the first study to immunolocalize a range of
these individual laminin chains (alpha 1, alpha 2, beta 1, beta 2, gamma 1) in
ovarian follicles. Frozen sections of bovine ovaries (n = 6) were immunostained
using specific antisera to laminin chains and factor VIII-related antigen (to
identify endothelial cells). Secondary antisera were labelled with one of two
different fluorochromes (DTAF and Cy3), and dual localization of laminin chains
and factor VIII-related antigen was performed. The alpha 1, beta 2 and gamma 1
chains were consistently localized to the follicular basal lamina in all healthy
follicles. Staining was less intense in the atretic antral follicles. Conversely,
alpha 2 and beta 1 were rarely present in the follicular basal laminae of healthy
antral follicles. Two of nine healthy antral follicles observed stained weakly
for alpha 2 in their basal lamina, and beta 1 was present at low concentrations
in growing preantral follicles. In atretic antral follicles, the follicular basal
lamina stained positively for alpha 1, alpha 2, and beta 2 but no beta 1 was
detected and the gamma 1 staining was less intense than in healthy follicles.
Antisera to Englebreth Holm-Swarm tumour laminin stained basal laminae of all
follicles. In the theca of antral follicles, beta 1 and beta 2 chains were both
present in the vasculature. Staining for the gamma 1 chain was present in the
thecal vasculature and generally throughout the theca of healthy and atretic
antral follicles. Therefore, the composition of the follicular basal lamina
alters during development and atresia, and potentially plays a role in the
changing identity of the granulosa cells and the accumulation of antral
follicular fluid.
PMID- 9640267
TI - Stimulation of ovarian oxytocin secretion and uterine prostaglandin release by
exogenous progesterone early in the cycle of the ovarian auto-transplanted ewe.
AB - The present study was undertaken to determine whether the administration of
progesterone, early in the oestrous cycle, had an influence on ovarian oxytocin
secretion and on peripheral concentrations of the prostaglandin F2 alpha
metabolite 13,14-dihydro-15-keto PGF2 alpha (PGFM) in the ovarian auto
transplanted ewe. Twelve ewes with ovarian auto-transplants (n = 6 per group)
were randomly assigned to receive an i.m. injection of progesterone (12.5 mg) or
vehicle, twice a day, on days 1, 2 and 3 of the oestrous cycle. Beginning on day
7, blood samples were collected at intervals of 1 h from the ovarian and
contralateral jugular veins for up to 70 h. Ovarian oxytocin secretion rate and
jugular concentrations of PGFM and progesterone were determined by
radioimmunoassay. The number of ewes that showed pulses of both ovarian oxytocin
and PGFM was significantly (P < 0.05) greater in progesterone-treated ewes than
in control ewes. In progesterone-treated ewes, the average number of ovarian
oxytocin pulses per ewe was 9.66 +/- 5.5 (mean +/- SD) and the interval between
pulses was 7.18 +/- 5.8 h. The mean amplitude and amount of oxytocin released, as
calculated by the area under the curve of ovarian oxytocin pulses, were 6.27 +/-
1.98 ng min-1 and (10.05 +/- 8.91 ng min-1)tau, respectively (where tau is the
number of hours between the last time point before and the first time point after
a significant increase in hormone concentration was detected by the Pulsar
program). The mean amplitude and area under the curve of PGFM pulses were 317.22
+/- 5.65 pg ml-1 and (383.36 +/- 1.77 pg ml-1)tau, respectively. The average
number of pulses of plasma PGFM observed per ewe was 5.8 +/- 1.9 and interpulse
interval for plasma PGFM pulses was 10.32 +/- 8.7 h between day 7 and day 9 after
oestrus. These data indicate that administration of progesterone during the first
3 days of the oestrous cycle results in the premature release of ovarian oxytocin
and uterine prostaglandin F2 alpha.
PMID- 9640268
TI - Development of oestrogen receptor expression and hormone response in the uterus
of the bovine fetus.
AB - The objective of the present study was to determine the temporal expression of
oestrogen receptor alpha in the uterus of the developing bovine fetus. Bovine
fetuses were collected and approximate gestational age was determined by crown
rump measurement. Fetal uteri were either snap frozen in dry ice-ethanol, or
placed in sterile Dulbecco's modified Eagle's medium. Fetal uteri (n = 20) were
homogenized and cytosolic oestrogen receptor measured by [3H]ligand binding
assay. Total RNA was extracted from fetal uteri (n = 53) and amplified by reverse
transcription-polymerase chain reaction using primers specific for the oestrogen
receptor, progesterone receptor, interleukin 1 alpha, interleukin 6, transforming
growth factor beta, prolactin receptor, epidermal growth factor receptor,
retinoic acid receptor isoforms alpha, beta, and gamma, or glyceraldehyde-3
phosphate dehydrogenase (loading control). Expressed as a ratio with
glyceraldehyde-3-phosphate dehydrogenase, mRNA encoding oestrogen receptor was
identified in fetal uteri throughout the period from day 65 to day 200, and was
increased from day 100 to day 185 (P < 0.003); uterine samples from day 100 to
day 200 expressed interleukin 1 alpha, interleukin 6, transforming growth factor
beta, prolactin receptor, epidermal growth factor receptor and retinoic acid
receptor isoforms alpha, beta, and gamma, but did not express detectable mRNA
encoding progesterone receptor. Despite the presence of mRNA encoding oestrogen
receptor, [3H]oestradiol binding was not detected until after day 155. Fetal
uterine explants collected at days 100-110 (n = 3) or at days 185-200 (n = 3)
were cultured in the presence of oestradiol (1.0 nmol l-1, or vehicle); there was
a significant effect of oestradiol treatment on specific mRNA expression at days
185-200 (P < 0.014), but not at days 100-110 (P = 0.71). It is concluded that
mRNA encoding oestrogen receptor is constitutively expressed at least from day 65
in the uterus of the bovine fetus, but that oestrogen receptor alpha protein and
a functional oestrogen response are not present until late in the second third of
pregnancy.
PMID- 9640269
TI - Doppler ultrasonography of canine maternal and fetal arteries during normal
gestation.
AB - Two-dimensional ultrasonography was used in combination with colour-flow imaging
and pulsed wave Doppler ultrasonography to study the maternal circulation and the
development of fetal vascularization in six Beagles during normal gestation. For
the first time, the development of the circulation was demonstrated in the bitch
and her fetuses intra vitam. The bloodstream was examined in small uteroplacental
arteries, the umbilical artery, the fetal aorta and the common carotid artery.
The duration of the study was from week 3 after insemination until birth.
Relatively large vessels were detected by cross-sectional ultrasonography, and
small vessels were detected by colour-flow imaging. In pulsed wave Doppler
ultrasonography, the blood flow was measured and described using the parameters
of systolic peak velocity, diastolic peak velocity, end-diastolic velocity,
pulsatility index, resistance index, A:B ratio (systolic peak velocity:end
diastolic velocity) and S:D parameter (systolic peak velocity:diastolic peak
velocity). The development of the measured parameters is typical and similar to
that in humans. The systolic peak velocity of the canine maternal uteroplacental
arteries shows important differences in comparison with humans. The pulsatility
index, resistance index and A:B ratio decrease in nearly all vessels. Only the
fetal common carotid artery has constant pulsatility and resistance indices
during gestation. For the first time, the quality and quantity of the normal
blood flow have been monitored during the whole of gestation. A normal
circulation is fundamental for supplying the fetus adequately with oxygen and
nutrients and thus for physiological development. These ultrasonographic results
are the basis for further clinical studies.
PMID- 9640270
TI - Differential effects of oestradiol and progesterone on proliferation and
morphology of cultured bovine uterine epithelial and stromal cells.
AB - The effect of oestrogen and progesterone on the proliferation of cultured bovine
uterine epithelial and stromal cells was assessed. Epithelial and stromal cells
recovered from cows at day 1 to day 3 of the oestrous cycle were cultured in RPMI
medium supplemented with 5% steroid-free fetal calf serum for 4 and 8 days. The
addition of progesterone to the culture medium altered the morphology of stromal
cells. Oestradiol (0.1-10 nmol l-1) and progesterone (50 nmol l-1) significantly
increased the total DNA (from 9.6 +/- 0.96 to 25.6 +/- 0.99 micrograms per well,
P < 0.001) and protein content (from 76.6 +/- 2.6 to 125.8 +/- 2.6 micrograms per
well, P < 0.001) and decreased the ratio of protein to DNA (from 8.0 +/- 0.24 to
4.9 +/- 0.24, P < 0.01) in stromal cells during the first 4 days. During the
second 4 days, the relative percentages of increase in DNA content were not
affected by steroids, indicating that the major effect of steroids on stromal
cell proliferation was exerted during the first 4 days of incubation. The
morphology of epithelial cells was not influenced by the addition of steroids.
DNA content of epithelial cells was reduced by the addition of oestrogen (from
22.9 +/- 2.1 to 15.0 +/- 2.0 micrograms per well, P < 0.01), but not progesterone
(from 22.9 +/- 2.1 to 25.8 +/- 2.0 micrograms per well, P > 0.05). Total protein
content of epithelial cells was reduced by oestradiol by day 4 (from 111.0 +/-
6.2 to 71.0 +/- 6.2 micrograms per well, P < 0.01), but not by day 8 (from 305.0
+/- 10.5 to 296.0 +/- 10.5 micrograms per well, P > 0.05). Progesterone increased
the total protein content (from 305.0 +/- 10.5 to 366.0 +/- 10.5 micrograms per
well, P < 0.01). Oestradiol significantly enhanced the ratio of protein to DNA in
epithelial cells at day 8 (from 10.1 +/- 1.0 to 16.8 +/- 1.0, P < 0.01). These
results show that oestradiol and progesterone have different effects on the
proliferation and morphology of epithelial and stromal cells in vitro.
PMID- 9640271
TI - Creatine metabolism in the seminiferous epithelium of rats. I. Creatine synthesis
by isolated and cultured cells.
AB - The testis synthesizes creatine from both arginine and glycine precursors, but
when rat testicular tissue is separated into seminiferous tubules and
interstitial cells, creatine synthesis occurs only in the tubular fraction. The
purpose of the work presented here was to define the locus of creatine synthesis
within the seminiferous tubules, by using cell separation and culture techniques
to examine synthesis in the Sertoli cells and germ cells. The total creatine
content, in the cellular compartment and incubation medium, of Sertoli-germ cell
co-cultures and of Sertoli cell-enriched cultures, largely free of germ cells,
increased by similar amounts over a 24 h incubation period. Sertoli cell-enriched
cultures incorporated radioactivity from L-[guanidino-14C]arginine and [1
14C]glycine into both creatine and its biosynthetic precursor, guanidinoacetic
acid. Isolated germ cells did not incorporate radioactivity from L-[guanidino
14C]arginine into either creatine or guanidinoacetic acid when incubated at a
similar density and protein concentration under similar conditions. It is
concluded that the synthesis of creatine observed in isolated rat seminiferous
tubules occurs within the Sertoli cells and not the germ cells.
PMID- 9640272
TI - Creatine metabolism in the seminiferous epithelium of rats. II. Effect of
modulators of cellular biochemical function on creatine secretion by cultured
Sertoli cells.
AB - The Sertoli cells have been identified as the primary locus for creatine
synthesis within the seminiferous epithelium. The purpose of the studies reported
here was to examine the effect of modulators of Sertoli cell function on creatine
secretion by primary cultures of these cells. Sertoli cell-enriched cultures,
maintained in a defined medium, secreted creatine into the incubation medium in a
manner that was linear with time over at least 6 h, but which had reached a
plateau within 24 h. Secretion was stimulated by physiological and toxicological
modulators of Sertoli cell function. Incubation of Sertoli cell-enriched cultures
in the presence of FSH (> or = 40 mU ml-1), dibutyryl cyclic AMP (> or = 0.1 mmol
l-1), mono-(2-ethylhexyl) phthalate (> or = 1 mumol l-1) or cadmium (> or = 3
mumol l-1) increased the secretion of creatine into the incubation medium by at
least 85% over 24 h. Creatine secretion by Sertoli cell-enriched cultures,
incubated over 4 h in a balanced salt solution, was independent of exogenous L
glutamine. However, the stimulation of secretion induced by 1 mmol dibutyryl
cyclic AMP l-1 was dependent on the presence of 4 mmol L-glutamine l-1 in the
incubation medium, which suggests that an increase in creatine secretion occurs
as a consequence of stimulated glutamine oxidation.
PMID- 9640273
TI - Concentrations of oxytocin in the intercavernous sinus of mares during
luteolysis: temporal relationship with concentrations of 13,14-dihydro-15-keto
prostaglandin F2 alpha.
AB - The reproductive tracts of nine thoroughbred mares were examined by ultrasound to
determine the day of ovulation (day 0). Mares were fitted with intercavernous
sinus cannulae on the day before the start of sample collection of pituitary
venous effluent rich in oxytocin. Intercavernous sinus blood samples were
collected for at least 36 h at 5 min intervals beginning at noon on day 13 (n =
2), day 15 (n = 5) or day 16 (n = 2) after ovulation. Concentrations of oxytocin
and 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM) in plasma were determined
by radioimmunoassay. Three high-magnitude surges of PGFM (> 1 ng ml-1) were found
in these samples. Three high magnitude pulses of oxytocin (> 200 pg ml-1) were
also observed, one associated with each of the PGFM surges. In each of these
cases, the oxytocin pulse appeared to follow or coincide with the onset of the
PGFM surge. Lower magnitude pulses of both hormones were detected throughout the
bleeding period in every mare. The average interval between these pulses was
122.3 min for oxytocin and 121.0 min for PGFM. The interval between pulses for
individual mares varied from 90 to 199 min for oxytocin, and from 87 to 213 min
for PGFM. However, there was no correlation between PGFM and oxytocin pulse
intervals among mares. Within each mare, there was no discernable association
between low magnitude pulses of oxytocin and PGFM. From these data, it was
concluded that high-magnitude surges of PGF2 alpha are associated with similar
surges of oxytocin from the posterior pituitary gland, and that PGF2 alpha may
induce their secretion. The posterior pituitary gland also appears to secrete
oxytocin in a pulsatile manner at a frequency of approximately 1 pulse every 2 h
but these pulses do not appear to be associated with the low magnitude pulses of
PGF2 alpha secreted from the uterus.
PMID- 9640274
TI - Central metabolic messengers and the effects of nutrition on gonadotrophin
secretion in sheep.
AB - Nutrition influences the reproductive axis via alteration of gonadotrophin
secretion. However, a link between nutrition and the secretion of GnRH, which
drives the axis, has yet to be established. The aim of the present study was to
measure the change in the concentrations of metabolic substances in the
cerebrospinal fluid of adult male sheep offered a diet designed to maintain
constant gonadotrophin secretion (Group M; n = 6), or a diet known to increase
gonadotrophin secretion (Group M + L; n = 6). On days 1, 3 and 10 of the dietary
treatments, cerebrospinal fluid and jugular blood were sampled and analysed for
metabolic fuels (glucose, amino acids and free fatty acids) and metabolic
hormones (insulin, insulin-like growth factor I, GH, prolactin, cortisol and the
thyroid hormones). On day 11 of the dietary treatment, LH pulse frequency and
mean FSH concentrations in Group M + L had increased relative to Group M and to
day 0. Plasma concentrations of prolactin and insulin on days 3 and 10, and
glucose and insulin-like growth factor I on day 10, were higher in Group M + L
than in Group M, but only cerebrospinal fluid concentrations of insulin, glucose
and certain amino acids were affected by the dietary treatments on days 3 and 10.
Cerebrospinal fluid, but not plasma, concentrations of aspartate, tyrosine,
cystine, phenylalanine and arginine on day 3, and glutamine, gamma-aminobutyric
acid, threonine, alanine on days 3 and 10, were higher in Group M + L relative to
Group M. On day 10, plasma and cerebrospinal fluid concentrations of arginine,
phenylalaine, proline, tyrosine, methionine and phosphoserine, but only the
plasma concentrations of linoleic acid, aspartate and serine, were higher in
Group M + L than in Group M. Concentrations of triiodothyronine, thyroxine, and
cortisol in plasma and cerebrospinal fluid were not affected. These results show
that the nutritional stimulation of gonadotrophin secretion is accompanied
primarily by fluctuations in plasma and cerebrospinal fluid concentrations of
insulin and certain amino acids, which suggests that, when nutritional status is
improved, insulin, amino acids and possibly glucose interact to modulate GnRH
secretion.
PMID- 9640275
TI - Dog epididymis-specific mRNA encoding secretory glutathione peroxidase-like
protein.
AB - A differential library screening procedure was used to clone a novel abundant and
tissue-specific cDNA from the dog epididymis. It was tentatively named CE7 for
dog epididymal gene product 7. By sequence similarity to homologous counterparts
expressed in mice, rats, pigs, and macaque monkeys, it appears that the 1.5 kb
dog epididymal mRNA encodes the secretory glutathione peroxidase-like protein,
GPX5. This protein is very similar to the family of glutathione peroxidase
enzymes, but does not contain selenocysteine. Northern blot and in situ
hybridization analyses revealed that the mRNA encoding CE7/GPX5, like its species
homologues, was restricted to the epididymis and transcribed by the epithelial
cells in the proximal parts of the organ. While the CE7 cDNA probe cross
hybridized to epididymal mRNAs in most species included in this study, it failed
to identify a human GPX5 counterpart. Northern blot analyses of epididymal RNA
extracts from hemi-cryptorchid dogs suggested that testicular secretions,
including androgen hormones, temperature effects, or both, were involved in the
region-dependent modulation of mRNA encoding CE7 in the dog epididymis. The
effect was most obvious in the caput region of the abdominal organ where the mRNA
encoding CE7 was almost completely downregulated.
PMID- 9640276
TI - Proteolysis of insulin-like growth factor-binding proteins (IGFBPs) within the
pig uterine lumen associated with peri-implantation conceptus development.
AB - Pig conceptuses undergo morphological development from spherical to filamentous
forms during days 10 to 12 of pregnancy, coincident with a high content of mRNAs
encoding insulin-like growth factor (IGF)-I in the uterine endometrium and
secretion of IGF-I into the uterine lumen. The potential regulation by developing
conceptuses of the bioavailability of IGF-binding proteins (IGFBPs) within the
uterine microenvironment was investigated. Uterine luminal flushings (ULFs) were
obtained between days 10 and 18 of pregnancy and the presence of specific IGFBPs
was detected by ligand blot analysis. ULFs collected at days 10 and 11 of
pregnancy contained 46 and 43 kDa IGFBP-3, several IGFBPs of about 30 kDa
including IGFBP-2, and an unidentified 26 kDa IGFBP; IGFBP-3 was the most
abundant. By day 12, however, IGFBPs were substantially diminished or
undetectable. Examination of the morphology of flushed conceptuses revealed that
the loss of IGFBPs in ULF was associated with the transition from spherical to
filamentous morphology. The abundance of IGFBP-3 mRNA in uterine endometrium, as
monitored by blot-hybridization, was not altered in a similar way, suggesting
that lack of IGFBP-3 in 'filamentous' ULF resulted from proteolysis rather than
from decreased expression of the IGFBP-3 gene. Consistent with this, incubation
of 'spherical' ULF with or without added 'filamentous' ULF at 37 degrees C
resulted in the disappearance of endogenous IGFBP-3 only in 'spherical +
filamentous' ULF. The protease activity in 'filamentous' ULF was inhibited by
EDTA, but unlike matrix metalloproteinases, was not zinc ion-dependent or
inhibited by 1,10-phenanthroline. Moreover, this activity was partially inhibited
by the serine protease inhibitor aprotinin, but not by 4-(2-aminoethyl)
benzenesulfonyl fluoride (AEBSF), a known inhibitor of plasmin. The IGFBP
protease activity of ULF may therefore comprise a group of enzymes including an
unidentified serine protease. The results suggest that elongating pig conceptuses
induce IGFBP protease activity which may increase the intrauterine
bioavailability of IGF.
PMID- 9640277
TI - Effect of follicle size and of the FecB Booroola gene on oocyte function in
sheep.
AB - Booroola ewes have a major gene that affects ovulation rate. Gene expression has
consequences on ovarian somatic cells but it is unknown whether it also affects
germ cells in the adult ovary. Hence, the present study examined (1) whether
oocyte growth was similar in FecBFecB and Fec+ Fec+ oocytes during preantral and
antral follicular growth, (2) whether the patterns of proteins neosynthesized by
oocytes of these two genotypes were identical, (3) whether the ability of the
oocytes to resume meiosis was unaffected by genotype and (4) whether, after IVF,
oocytes from both genotypes could develop to the blastocyst stage at similar
rates. Histological examination of the respective sizes of the oocyte and of the
follicle demonstrated that oocytes were larger in FecBFecB versus Fec+ Fec+
preantral follicles. Resolution of the proteins neosynthesized by FecBFecB and
Fec+ Fec+ oocytes by one-dimensional PAGE and image analysis demonstrated that
quantitative (but not qualitative) differences could be observed between
genotypes for bands at 74, 59, 35 and 25 kDa. In addition, a genotype by oocyte
size interaction was detected for two additional bands at 45 and 43 kDa. After 24
h of culture in vitro in TCM-199 plus 100 ng ml-1 FSH plus 10% sheep follicular
fluid, oocytes from FecBFec+ follicles gained the ability to resume meiosis at a
smaller size and a higher proportion of them reached metaphase II irrespective of
the size class studied compared with Fec+ Fec+ follicles. In addition, the
developmental rate of eggs after IVF was also affected by follicle size and
genotype, since FecBFec+ oocytes originating from 1.0-3.5 mm follicles had a
greater ability (P < 0.05) to develop to the blastocyst stage than Fec+ Fec+
oocytes. It is concluded that the FecB gene, in addition to its effects on
granulosa cell maturation, also affects oocyte development and function. Whether
these alterations are related requires further investigation.
PMID- 9640278
TI - Expression of RNA from developmentally important genes in preimplantation bovine
embryos produced in TCM supplemented with BSA.
AB - This study investigated the effects of a semi-defined culture system on the
temporal pattern of expression of RNA from genes involved in compaction and
cavitation: gap junction protein connexin43 (Cx43), desmosomal glycoproteins
desmoglein 1 (Dg 1), desmocollins I, II and III (Dc I, Dc II, Dc III), desmosomal
protein plakophilin (Plako); metabolism glucosetransporter-1 (Glut-1); RNA
processing poly(A)polymerase (PolyA); heat shock protein 70.1 (HSP); and
trophoblastic function trophoblast protein (TP) in bovine oocytes and embryos
generated in vitro using TCM199 supplemented with BSA as the culture medium.
Morulae and blastocysts derived in vivo were collected from superovulated heifers
and also used for this study. Poly(A)+ RNA was extracted from pools of 20-50
oocytes or embryos, analysed by reverse transcription-polymerase chain reaction
and the amplified fragments were verified by sequencing. Assays were repeated at
least three times for each developmental stage and provided consistent results in
all replicates. In bovine embryos produced in vitro, mRNA encoding Cx43 was
detectable up to the morula stage, whereas blastocysts and hatched blastocysts
did not express this gene. No transcripts were found for Dg 1 and Dc I throughout
the tested preimplantation stages. Dc II and Dc III transcripts were found from 2
4-cell embryos up to the hatched blastocyst stage. mRNA encoding Plako was
detected in immature and mature oocytes and zygotes, while no transcripts were
seen in 2-4-cell and 8-16-cell embryos. The gene was expressed again from the
morulae to the hatched blastocyst stage. Oocytes and bovine embryos produced in
vitro showed transcripts for Glut-1, PolyA and HSP throughout preimplantation
development up to the hatched blastocyst stage. The gene encoding TP was
transcribed only in blastocysts and hatched blastocysts. Morulae and blastocysts
produced in vivo showed the same expression as their in vitro counterparts, with
one exception: the in vivo embryos transcribed Cx43. The results of this study
reveal for the first time the transcriptional pattern of a set of 'marker' genes
involved in various processes in early bovine embryonic development. Transferable
morulae and blastocysts produced in vitro expressed most genes similar to their
in vivo counterparts. These data contribute to the molecular characterization of
this widely used in vitro culture system for bovine embryos and provide a major
advance towards production of 'physiologically normal' embryos.
PMID- 9640279
TI - Photoperiod-induced phase-shifts of the endogenous clock controlling reproduction
in the rainbow trout: a circannual phase-response curve.
AB - Different groups of winter-spawning female rainbow trout that had been maintained
under seasonally changing daylength and temperature were exposed to 2 months of
continuous light at different times of the year. The same photoperiod produced
advances in the time of spawning of up to 232 days and delays of up to 80 days,
depending upon the timing of exposure in relation to the phase of the
reproductive cycle. The proportion of fish spawning in each group varied from 18%
to 100%, again dependent on the timing of exposure to continuous light. The
photoperiod-induced changes in spawning time can be interpreted as phase
dependent phase-shifts of an endogenous circannual clock controlling maturation.
It is proposed that long days, occurring earlier or later than they would under a
natural photoperiod, were perceived as indications that the clock was running
slow or fast, thus initiating corrective forward adjustments (advance phase
shifts) or backward adjustments (delay phase-shifts), respectively. Collectively,
these responses can be described in the form of a circannual phase-response
curve.
PMID- 9640280
TI - Introducing an integrated imaging delivery system in Manitoba.
AB - OBJECTIVE: As a result of the reform of a comprehensive government health plan,
an integrated imaging system is being created in the province of Manitoba. The
intent of the system is to reduce costs, avoid causing harm to patients, enhance
physician referral services and add new programs. METHODS: Evaluation of trends
in examinations, equipment, personnel, expenditures and policy in the 1992-93 and
1995-96 fiscal years in Manitoba. RESULTS: The population has remained steady, at
1.1 million. Hospitals have been amalgamated under new authorities, and
Manitoba's annual health care spending of $1.8 billion has been reduced by $235
million. Between the 2 years, use of radiography declined from 835,748 to 726,394
examinations per year. Use of mammography, ultrasonography, computed tomography,
magnetic resonance imaging and nuclear medicine increased moderately. The total
number of radiologic examinations declined from 1,069,579 to 975,044. There was
little change in equipment, but the plant aged as a result of freezes on
construction and capital spending. Personnel declined by 20 full-time equivalent
positions, from 794.3 in 1992-93 to 774.3 in 1995-96. Savings in operations were
made as a result of hospital budget restrictions. Total expenditures declined
from $100 million to $89 million. The income of imaging specialists did not
change because they were paid higher fees for examinations involving newer
technology. CONCLUSION: Integration of rural/northern and urban hospital services
has followed the plan set out in recent legislation. Savings of up to 20% are
expected to be realized through reduction in personnel (saving $1 million), group
tendering ($1 million), in-house repair ($1 million), reduction in deployment of
equipment ($3 million), integration of services ($1 million), indirect cost
reduction ($5 million), practice guidelines ($3.5 million), reduced breast
screening costs ($1 million), physician payment reform ($1 million) and rigorous
clinical/fiscal audit ($1 million).
PMID- 9640281
TI - Metformin and contrast media: where is the conflict?
AB - Intravascular administration of iodinated contrast media to patients who are
receiving metformin, an oral antidiabetic agent, can result in lactic acidosis.
However, this rare complication occurs only if the contrast medium causes renal
failure, and the patient continues to take metformin in the presence of renal
failure. Because metformin is excreted primarily by the kidneys, continued intake
of metformin after the onset of renal failure results in a toxic accumulation of
this drug and subsequent lactic acidosis. To avoid this complication, metformin
must be withheld after the administration of the contrast agent for 48 hours,
during which the contrast-induced renal failure becomes clinically apparent. If
renal function is normal at 48 hours, the metformin can be restarted. There is no
scientific justification for withholding metformin for 48 hours before
administration of the contrast medium, as currently recommended in the package
insert. The authors review the pharmacology of metformin and present a
departmental policy for managing patients with diabetes who receive metformin and
who require intravascular administration of iodinated contrast media.
PMID- 9640282
TI - Consultation skills in radiology: a qualitative study.
AB - OBJECTIVE: Consultation is an important part of radiologic practice. Recently,
many concerns have been expressed about the lack of emphasis on consultation
skills as part of the training requirements for radiologists. In order to improve
the teaching and assessment of trainees, we designed a qualitative study to
specify the consultation skills expected from a trainee by the end of residency.
METHODS: Three successive focus groups were held with professors of radiology,
residents in radiology, and referring physicians. Participants were asked to
identify the various competencies required from radiologic consultants (1)
spontaneously, (2) by reacting to a previously generated list, and (3) by
reacting to common clinical problems encountered in radiology. RESULTS:
Consultation skills thus identified were organized in a framework consisting of 2
groups: observable skills and standards of practice. Observable skills were
subdivided into 5 "problem-setting" skills and 6 "results-management" skills.
Seven qualities and attitudes identified were combined under the rubric
"standards of practice." CONCLUSION: The specification of these abilities and
competencies through a consensus process should permit the teaching of these
skills and their evaluation through objective, structured clinical examinations.
PMID- 9640283
TI - Gestational breast cancer.
AB - OBJECTIVE: To study the problems of breast imaging in gestational breast cancer.
PATIENTS AND METHOD: Retrospective review of the charts of 19 patients with
breast cancer detected during pregnancy or lactation or within 1 year of
delivery, who were referred to a tertiary centre for adjuvant therapy between
1986 and 1996. For 10 patients who underwent breast imaging, mammograms and
breast ultrasonograms or reports were requested from outside facilities. RESULTS:
The patients ranged in age from 23 to 41 years (mean 31 years). All 19 patients
presented with palpable tumours; in 7 patients, the tumours were stage T2 or
higher; in 11 patients, the tumours were at an advanced stage with positive
axillary nodes. In 11 of the patients there was a delay in diagnosis, which
ranged from 2 to 16 months. Of the 8 mammograms that could be reviewed, 5 showed
infiltrating ductal carcinomas with typical features, which were detected as a
mass (in 1 case), a mass with microcalcifications (in 1 case),
microcalcifications (in 2 cases) and asymmetry (in 1 case). Three mammograms were
negative, including 1 obtained from a patient with extensive comedocarcinoma.
Breast ultrasonograms obtained from 4 patients (2 of whom also had mammograms)
showed solid hypoechoic masses; in 2 of the ultrasonograms, the masses simulated
a benign lesion. CONCLUSIONS: Although breast cancer during pregnancy and
lactation is rare, this study suggests that radiologists should include it in the
differential diagnosis of a solid breast mass seen during pregnancy or lactation.
Clinicians appear to be reluctant to use breast imaging in these patients;
however, this can lead to a delay in diagnosis. Ultrasonography is the modality
of choice for initial analysis of such a mass in this age group. Mammography with
shielding of the abdomen is recommended if there is suspicion of cancer.
Clinical, mammographic and sonographic findings should be integrated for optimum
interpretation.
PMID- 9640284
TI - Aneurysm of coronary artery bypass graft presenting as a mediastinal mass: case
report.
PMID- 9640285
TI - Choroidal melanoma metastasis as a rare cause of cerebellopontine angle lesion: 2
case reports.
PMID- 9640286
TI - Coats' disease (exudative retinopathy): case report.
PMID- 9640287
TI - Comparison of digital angiographic images with conventional radiographs for
detection of pneumothorax after needle biopsy of lung.
AB - OBJECTIVE: To compare the rate of detection of pneumothoraces from images
obtained from a digital angiographic system (1024 x 1024 matrix) and from
conventional film-screen chest radiographs, following fine-needle biopsy of the
lung. PATIENTS AND METHOD: For 102 patients who underwent fine-needle biopsy, 2
digital fluoroscopic chest images and 1 film-screen chest radiograph were
obtained during expiration after the biopsy. The images were interpreted by 4
blinded readers. RESULTS: There were 30 pneumothoraces, of which 96.6% were
detected from standard chest radiographs and 54.2% were detected from digital
images. CONCLUSIONS: The detection of pneumothorax from digital images was far
inferior to that from standard film-screen chest radiographs. Therefore, standard
chest radiographs are recommended after fine-needle biopsy of the lung.
PMID- 9640288
TI - Check-valve pneumatocele formation following fully treated tuberculosis: case
report.
PMID- 9640289
TI - Residents' corner. Answer to case of the month #55. Intrathoracic extramedullary
hematopoiesis secondary to idiopathic myelofibrosis.
PMID- 9640290
TI - Telehealth in home care practice.
PMID- 9640291
TI - North Central West Virginia Nursing Workforce Network.
PMID- 9640292
TI - Creating value for patients. A legal perspective.
PMID- 9640293
TI - Developing a nursing outcomes measurement tool.
AB - In an era of rapidly shifting resources and changing models of care, healthcare
providers must demonstrate quality and cost-effective patient care. Historically,
quality of care has been described using administrative variables such as
mortality, morbidity, length of stay, readmissions, and cost. Methods have not
been readily available to define quality in terms of the effect of care delivery
on the health of patients. Combined administrative and health-related databases
are foundational to outcome infrastructures evolving with the electronic medical
record. Nursing leaders in a large health maintenance organization sponsored the
development of the Health Status Outcome Dimensions (HSOD) instrument. The HSOD
instrument includes measures of functional status, knowledge, and engagement in
healthcare and the patient and family psychosocial well-being. This article
describes the processes used and the challenges faced in the development of the
HSOD instrument. The current status of the HSOD instrument is described, as well
as its planned future development.
PMID- 9640294
TI - Nurse executives' leadership roles. Perceptions of incumbents and influential
colleagues.
AB - The authors present a leadership profile of employed nurse executives (NEs).
Interviews and survey data show that the typical NE is a married, middle-aged
woman who has a masters degree in clinical nursing and extensive clinical
experience. When comparing NEs' and influential colleagues' perceptions of the
effectiveness of NEs leadership skills, the former rate themselves higher than
the latter, and both groups perceive that NEs' leadership styles are more "task
motivated" than "relationship motivated." The authors apply these findings to the
career planning of NEs, chief executive officers, and educators in healthcare
fields.
PMID- 9640295
TI - Disaster preparedness pays off.
AB - Last spring, the Red River Valley of North Dakota and Minnesota was devastated by
an unprecedented flood. Flooding caused foundations to collapse and houses to
float away or become severely damaged by the raging, sewage-filled water. The
river displaced people from their homes, and caused significant disruption of
services including water, power, and medical care for 18 days. Find out how a
medical contingency plan enabled staff members at the only trauma center and the
largest clinic in the region to evacuate safely and effectively nearly 1,000
patients and senior residents in 36 hours, while setting up critical services
across the region to care for the 50,000 displaced residents of the flood
disaster.
PMID- 9640296
TI - The changing nature of organizational commitment in the acute care environment.
Implications for nursing leadership.
AB - The downsizing of the acute care sector of healthcare is providing hospital
nursing staff with fewer alternative employment options in the areas in which
they currently work. This greater employment uncertainty is likely to affect the
variables that organizational behaviorialists have found to both enhance or
detract from the organizational commitment that staff members feel toward the
organization. The author analyzes the latent effects of the progressive changes
being sustained in acute care work markets that influenced nurses' perceived
levels of organizational commitment in earlier times. The research conducted in
this field by both nursing and other disciplines is reviewed, and implications
are proposed.
PMID- 9640297
TI - Bowen's family systems theory. A useful approach for a nurse administrator's
practice.
AB - Two concepts from Bowen's family systems theory are differentiation of self and
triangles. These concepts are presented and recommended as useful tools for the
nurse a administrator. By using the principles from differentiation of self,
nurse administrators may improve the work environment by distinguishing between
their own thoughts and feelings. Once a nursing administrator identifies and
changes triangulation processes, healthy relationship patterns may occur and
staff absenteeism and low morale may be improved.
PMID- 9640298
TI - Community collaboration. The nursing administrator's role in implementing a child
abuse prevention program.
AB - The increasing incidence of child abuse is a national disaster. One proposed
intervention is prevention through a public health nurse home visitation program
developed and extensively researched by David Olds. Selected components of the
conceptual model of community collaboration developed by Polivka are applied to
the implementation process. The role of the public health nursing administrator
in collaboration, human resource management, and delegation is discussed.
PMID- 9640299
TI - Kidney disease in Australian aboriginals: time for decisive action.
PMID- 9640300
TI - Wernicke's encephalopathy and thiamine fortification of food: time for a new
direction?
PMID- 9640301
TI - Australian medical research: more resources and the right balance.
PMID- 9640302
TI - An epidemic of renal failure among Australian Aboriginals.
AB - OBJECTIVE: To define recent trends (1993-1996) in incidence of endstage renal
disease (ESRD) among Australian Aboriginal people in the Top End of the Northern
Territory (NT). DESIGN: Analysis of hospital and clinical records of the Darwin
based ESRD treatment program from 1993 to 1996 and comparison with data
accumulated since 1978. PARTICIPANTS: All people entering the ESRD treatment
program from 1978 to 1996. MAIN OUTCOME MEASURES: Number of patients treated for
ESRD; their ethnicity, age and sex; comorbidities in Aboriginal patients;
treatment methods and outcomes. RESULTS: More Aboriginal people presented with
ESRD between 1993 and 1996 (87) than in the previous 15 years of the program
(68). The incidence of ESRD in Aboriginals reached 838 per million in 1996, and
is doubling every 4 years. Aboriginal people presenting with ESRD are younger
than non-Aboriginal people with ESRD, and, in contrast to non-Aboriginals, ESRD
rates are higher in women than men. The numbers and proportions of Aboriginal
ESRD patients who have hypertension, type 2 diabetes and cardiac disease are
rising. Haemodialysis remains the most common form of treatment, and the number
of dialysis treatments is doubling every 2.5 years. Only 9% of Aboriginal
patients entering the program in 1993-1996 were treated with chronic ambulatory
peritoneal dialysis and only 3% received transplants. Despite their younger age,
survival of Aboriginal people on dialysis is low (median 3.3 years v. 6.5 years
in non-Aboriginals), and graft survival after transplant is poor (37% at 5 years
v. 88% in non-Aboriginals). Survival has not improved in the past 4 years, with
fewer deaths from infection offset by more deaths from cardiovascular disease.
CONCLUSIONS: The predicted doubling of ESRD incidence among Aboriginal people by
the year 2000 will add an enormous burden to limited resources. Risk factors for
renal disease underlie all the excess morbidity and mortality in NT Aboriginal
adults, and arise out of accelerated lifestyle changes and socioeconomic
disadvantage. Better living conditions and education, robust and integrated
primary healthcare programs, and systematic screening for early renal disease and
treatment of those with established disease are all matters of urgency.
PMID- 9640303
TI - Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine
fortification made a difference?
AB - OBJECTIVE: To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS)
in Australia and compare this with previous studies. DESIGN AND SETTING:
Prospective autopsy study at the New South Wales Institute of Forensic Medicine,
1996-1997. METHODS: Brains of deceased people (aged over 15 years) derived from
2212 sequential autopsies performed between 1 January 1996 and 31 December 1997
were studied macroscopically and microscopically to identify cases of WKS. MAIN
OUTCOME MEASURES: Standard histological criteria for WKS and any available
clinical data. RESULTS: Twenty-five cases of WKS were identified (prevalence,
1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of
alcohol abuse. Only four cases (16%) had been diagnosed during life. CONCLUSIONS:
There has been a significant reduction in the prevalence of WKS in Australia
since the introduction of thiamine enrichment of bread flour. While the
prevalence is still higher than in most other Western countries, further research
is needed before adding thiamine to alcoholic beverages can be recommended.
PMID- 9640304
TI - Measles-mumps-rubella and hepatitis B vaccination uptake in adolescents: a survey
in metropolitan Melbourne.
AB - OBJECTIVE: To measure the uptake of preadolescent measles-mumps-rubella (MMR) and
adolescent hepatitis B vaccinations and assess the influence of certain
demographic factors on the uptake of these vaccines. DESIGN: Prevalence surveys
of uptake rates of preadolescent (school Year 6; age 10-11 years) MMR and
adolescent (school Year 9; age 13-14 years) hepatitis B vaccination. SETTING:
City of Darebin, an inner northern metropolitan region of Melbourne, 1996.
SUBJECTS: 1160 Year 6 school students (580 boys) and 1102 Year 9 school students
(548 boys). INTERVENTION: School-based vaccination program administered by
Darebin Council. RESULTS: 83% of Year 6 students were vaccinated with the MMR
vaccine (84.1% of girls and 81.9% of boys). 71.6% of Year 9 students completed
the full course of hepatitis B vaccination (68.9% of boys and 74.2% of girls).
There was a higher uptake of MMR in non-government primary schools, but no other
demographic factors (sex, economic status, non-English-speaking background,
parental education, school class size) were associated. CONCLUSIONS: These uptake
rates do not meet National Health and Medical Research Council (NHMRC)
recommendations. Further study is required to determine and quantify the factors
that affect vaccination uptake in adolescence. Programs may then be developed to
improve vaccination uptake.
PMID- 9640305
TI - Haemolytic-uraemic syndrome outbreak caused by Escherichia coli O111:H-: clinical
outcomes.
AB - In South Australia in 1995, we treated 20 children with haemolytic-uraemic
syndrome associated with Escherichia coli O111:H-. The source of the outbreak was
contaminated locally produced semi-dry fermented sausage (mettwurst). One child
died of multiple haemorrhagic cerebral infarcts. Eighteen children required renal
dialysis (for a median of 14 days); 12 months after discharge five still had
significant impairment of renal function. Other major complications included
colonic necrosis (3), cerebral haemorrhage/infarction (3), convulsions (4), and
glucose intolerance (2). Although E. coli O111:H- has been associated with
sporadic cases of haemolytic-uraemic syndrome, this was the first large outbreak
reported in Australia.
PMID- 9640306
TI - Casemix funding in Australia.
AB - Casemix funding for hospitals with the use of diagnosis-related groups (DRGs),
which organise patients' conditions into similar clinical categories with similar
costs, was introduced in Australia five years ago. It has been applied in
different ways and to a greater or lesser extent in different Australian States.
Only Victoria and South Australia have implemented casemix funding across all
healthcare services. Attempts have been made to formally evaluate its impact, but
they have not met the required scientific standards in controlling for
confounding factors. Casemix funding remains a much-discussed issue. In this
Debate, Braithwaite and Hindle take a contrary position, largely to stimulate
policy debate; Phelan defends the casemix concept and advocates retaining its
best features; and Hanson adds a plea for consumer input.
PMID- 9640307
TI - Essential gastroenterology for the non-gastroenterologist.
PMID- 9640308
TI - Acute viral hepatitis.
AB - Most cases of acute hepatitis are caused by hepatitis viruses A, B or C.
Diagnosis rests on the risk factor history and serological tests. In seronegative
cases, consider other agents, such as Epstein-Barr virus and cytomegalovirus,
drug reactions and autoimmune hepatitis. Hepatitis A and B can be prevented by
appropriate use of highly effective, safe vaccines. Acute liver failure is an
uncommon, devastating complication of acute viral hepatitis; continued vomiting,
prolongation of prothrombin time and clouding of consciousness are indications
for urgent transfer to a liver transplant unit. Hepatitis A is a simple,
enterically transmitted illness that does not cause chronic hepatitis. 95% of
adults recover from acute hepatitis B, whereas infection with hepatitis B virus
acquired in childhood usually becomes chronic.
PMID- 9640309
TI - Managing somatoform disorders.
AB - The management of somatoform disorders is a confusing and difficult area. There
are many iatrogenic complications, including unnecessary and repetitive
investigations and surgery, drug dependence and "doctor shopping". Somatisation
is a world wide phenomenon and a common presentation of psychological distress.
Three main groups of patients are encountered in general practice: those with
high levels of somatic symptoms, those with illness fear, and those with somatic
presentations of other psychiatric illnesses. Management is straightforward for
the acute cases and consists of trying to get the patient to accept a link
between the psychosocial conflicts and the symptoms. Management is very difficult
for chronic cases, where care, not cure, is the goal, as is an attempt to limit
harm to the patient and limit the cost to the health system.
PMID- 9640310
TI - GM-CSF and wound healing.
PMID- 9640311
TI - Rationing in Australian health care services.
PMID- 9640312
TI - Stress management and counselling in primary care.
PMID- 9640313
TI - Echinacea-associated anaphylaxis.
PMID- 9640314
TI - Treating stingray wounds with onions.
PMID- 9640315
TI - Indications for liver transplantation.
PMID- 9640316
TI - Once is enough--why some women do not continue to participate in a breast cancer
screening programme.
AB - AIM: To assess the reasons why many women who have been screened once in a breast
screening programme decline an invitation for further screening. METHODS:
Telephone interview survey of a sample of such women; for questions relating to
their experience of previous mammography, comparison to data on a representative
sample of first screen attendees. The subjects were women who had attended the
first round of the Otago-Southland breast cancer screening programme in 1991
1994, who were eligible for re-screening but had been rescreened; age range 50
62. RESULTS: From programme records, 86% of women who were eligible for a second
screen accepted it. Of the women not recorded as having had a second screen, some
had attended for a second screen; some had not been invited until they had become
age ineligible and some had received no invitation for re-screening. Of women who
had received and declined an invitation for re-screening (n = 81), the major
reason (46%) was their previous mammogram being painful. Other factors
contributing were illness in themselves or their spouse, practical difficulties
arranging time and negative experiences with staff in the previous mammography,
although these related to relatively few women. A few women thought mammography
would be of no benefit, and a few thought re-screening was unnecessary because
their first mammography had been normal, or because they practise self
examination. CONCLUSIONS: Ensuring that all women eligible for further screening
do get invited could substantially increase the re-screening rate. Even women who
have declined previous invitations should be offered further invitations, as a
substantial proportion with to be screened. Flexible and convenient appointment
times are the main modifiable logistic issue. The major factor influencing non
participation with further screening is a painful experience of mammography.
Innovative approaches, either to reduce the pain or to reduce the impact of the
pain on the woman's attitude to re-screening, should be trialed.
PMID- 9640317
TI - Current airway clearance techniques.
AB - In recent times, airway clearance has become an increasingly important part of
the treatment of patients with excessive bronchial secretions, especially those
with cystic fibrosis. The number of airway clearance techniques available has
also grown considerably, becoming increasingly more specific. This has allowed
patients a greater choice of treatment techniques and has led to a subsequent
rise in independence. This paper gives a brief overview of the methods of airway
clearance currently being used by physiotherapists in New Zealand. To date, no
one method has been shown to be more effective than another. It is imperative
therefore, that those involved in respiratory care have a clear understanding of
the airway clearance techniques available. This will allow us to provide out
patients with the best possible treatment option.
PMID- 9640318
TI - Paediatric exploratory ingestions of paracetamol.
AB - AIM: To review paediatric exploratory ingestions of paracetamol presenting to
Christchurch Hospital Emergency Department. METHOD: A retrospective review of all
paediatric patients presenting with paracetamol ingestion over a 12 month period.
RESULTS: During the study period there were 88 paediatric presentations for
possible toxic ingestions involving paracetamol and 85 of these were exploratory
self-ingestion. The male to female ratio was 43:42 and the mean age was 35
months. Paracetamol suspension was ingested in 79/85 cases and tablets in 6/85.
The mean four hour plasma level was 162 mumol/L and all levels were well below
the possible toxic level (1300 mumol/L). There was very poor correlation between
estimated dose ingested and plasma level. CONCLUSION: Toxicity from paediatric
exploratory ingestion of paracetamol is extremely rare. To reduce the potential
for poisoning, bottles and prescriptions of paracetamol should have less than a
total dose of 4 g. The authors recommend that unwitnessed exploratory ingestions
of paracetamol in children require no treatment if the estimated maximum ingested
dose is below 140 mg/kg. Above this dose, treatment is based on the result of a
plasma paracetamol level drawn four hours after ingestion. Gastrointestinal
decontamination should be reserved for the rare occasions of a definite witnessed
ingestion of a dose exceeding 140 mg/kg.
PMID- 9640319
TI - What do general practitioners do when patients present with symptoms indicative
of urinary tract infections?
AB - AIM: The primary aim of the study was to examine whether the results of
laboratory investigations of midstream urine samples from patients with suspected
urinary tract infection influenced management by general practitioners. METHOD:
Eleven general practitioners in the Network participated in the study by
recording treatment and outcomes for consecutive patients with symptoms of
urinary tract infection. RESULTS: Data from 216 patients were included in the
study. Dipsticks were used to test the urine of 98 patients (45%) and midstream
urine samples were sent to the laboratory for 176 patients (82%). Antibiotics
were prescribed for 176 patients (82%). Antibiotics were prescribed for 95% of
patients with symptoms of dysuria, frequency and urgency. Where the laboratory
results showed infection there was no change in treatment after the general
practitioners received the results for 75 patients (85%). Among those patients
where the laboratory reported no infection there was no change in treatment after
the general practitioner received the results for 53 patients (87%). CONCLUSIONS:
The results of laboratory investigation of midstream urine samples did not change
the treatment provided for the majority of patients in the study.
PMID- 9640320
TI - Experience of the upright breast stereotactic core biopsy method and histological
correlation with surgical biopsy.
PMID- 9640321
TI - Pathological fracture in an 87-year-old woman.
PMID- 9640322
TI - Tamoxifen for breast pain.
PMID- 9640323
TI - Youth suicide rates.
PMID- 9640324
TI - Statins.
PMID- 9640325
TI - Ischaemic nephropathy.
PMID- 9640326
TI - Pharmac--what next?
PMID- 9640327
TI - Hepatitis TT virus is present in New Zealand.
PMID- 9640328
TI - Xenopus Smad7 inhibits both the activin and BMP pathways and acts as a neural
inducer.
AB - Smads are proteins that transduce signals on behalf of members of the TGF beta
superfamily of growth factors. Recently, inhibitory Smads, Smad6, Smad7, and Dad,
were isolated from human, mouse, and fly. These anti-Smads were shown to inhibit
TGF beta signaling by stably associating to TGF beta type I receptors or, as it
was shown for Smad6, by binding to receptor-activated Smad1. We report the
cloning, distribution, and embryological activity of the Xenopus Smad7 (XSmad7).
We report that XSmad7 inhibits signaling from the activin and BMP pathways in
animal explants although at different thresholds. When expressed in the embryo,
low concentrations of XSmad7 dorsalize the ventral mesoderm, thus inducing a
secondary axis. At higher concentrations however, XSmad7 inhibits both mesoderm
induction and primary axis specification. In addition, we show that XSmad7 acts
as a direct neural inducer both in the context of ectodermal explants and in
vivo. We discuss the implications of these findings in the biochemical context of
the activin and BMP pathways as well as their implications in mesodermal, neural,
and axis specification.
PMID- 9640329
TI - Disregulation of ocular morphogenesis by lens-specific expression of FGF-3/int-2
in transgenic mice.
AB - FGF-3, originally named int-2, was discovered as an oncogene frequently activated
in mammary carcinomas resulting from the chromosomal integration of the mouse
mammary tumor virus (MMTV). Int-2 was later designated FGF-3 based on sequence
homology with other members of the fibroblast growth factor (FGF) family. FGF-1
is the prototypical member of the FGF family, and is the only family member which
activates all known FGF receptor isoforms. Transgenic mice expressing in the lens
a form of FGF-1 engineered to be secreted show premature differentiation of the
entire lens epithelium. In contrast, transgenic mice engineered to secrete FGF-2
in the lens do not undergo premature differentiation of the lens epithelium (C.
M. Stolen et al., 1997, Development 124, 4009-4017). To further assess the roles
of FGFs and FGF receptors in lens development, the alpha A-crystallin promoter
was used to target expression of FGF-3 to the developing lens of transgenic mice.
The expression of FGF-3 in the lens rapidly induced epithelial cells throughout
the lens to elongate and to express fiber cell-specific proteins including MIP
and beta-crystallins. This premature differentiation of the lens epithelium was
followed by the degeneration of the entire lens. Since FGF-1 and FGF-3 can both
activate one FGF receptor isoform (FGFR2 IIIb) that is not activated by FGF-2,
these results suggest that activation of FGFR2 IIIb is sufficient to induce fiber
cell differentiation throughout the lens epithelium in vivo. Furthermore,
transgenic lens cells expressing FGF-3 were able to induce the differentiation of
neighboring nontransgenic lens epithelial cells in chimeric mice. Expression of
FGF-3 in the lens also resulted in developmental alterations of the eyelids,
cornea, and retina, and in the most severely affected transgenic lines, the
postnatal appearance of intraocular glandular structures.
PMID- 9640330
TI - Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart
development.
AB - Connexin 43 (Cx43) knockout mice and transgenic mice (CMV43) overexpressing the
Cx43 gap junction gene exhibit heart defects involving the conotruncus and right
ventricle. Based on the heart phenotype and Cx43 gene and transgene expression
pattern, we previously proposed that the heart defects may reflect a role for gap
junctions in the modulation of cardiac neural crest development. To further
elucidate the mechanism by which these heart defects may arise, fetal heart
structure and function in these transgenic and knockout mice were examined by
magnetic resonance microscopy and Doppler echocardiography. Magnetic resonance
microscopy of E14.5 fetuses revealed an enlargement of the right ventricular
chamber in the heterozygous Cx43 knockout and CMV43 transgenic mice. This was
accompanied by thinning of the chamber wall. In the homozygous Cx43 knockout
mouse, heart malformation was also restricted to the right ventricle. This was
generally characterized by two pouches at the base of the pulmonary outflow
tract, but occasionally hearts with a single pouch were found. Magnetic resonance
microscopy showed in some of the CMV43 and Cx43 knockout mice an attenuation of
the ductus arteriosus, a phenotype which may be indicative of outflow tract
obstruction. This was confirmed by the in utero Doppler echocardiography, which
showed increased outflow velocity in E12.5 to 14.5 CMV43 and Cx43 knockout
fetuses. In some of these fetuses, Doppler analysis also revealed arrhythmia and
absence of isovolemic contraction time. Further examination of these hearts by
histology and immunohistochemistry showed abnormal myocardial development in the
conotruncus. Particularly interesting was the presence of abundant subendocardial
fibrous tissue expressing smooth muscle actin. In the developing heart, such
mesenchyme in the outflow tract is usually considered neural crest-derived
tissue. Together, these results confirm the importance of Cx43 gene dosage in
conotruncal heart development and suggest that this likely involves a role for
Cx43 gap junctions in cardiac crest development. In future studies, these
transgenic mice may serve as valuable animal models for further studying the role
of gap junctions and cardiac crest cells in conotruncal heart development.
PMID- 9640331
TI - Roles of secretion and the cytoskeleton in cell adhesion and polarity
establishment in Pelvetia compressa zygotes.
AB - During the establishment of polarity, fucoid algal zygotes adhere to the
substratum and select a growth axis according to environmental cues. Since little
is known about the early events leading to axis selection, we investigated the
chronology of cell adhesion, adhesive deposition, and axis selection induced by
light (photopolarization). The requirements for secretion and the cytoskeleton in
these processes and in the process of changing the orientation of an axis in
response to new environmental cues (axis realignment) were also tested. Adhesive
deposition occurred in two distinct stages: it was deposited uniformally on young
zygotes (uniform primary adhesive) and later was deposited asymmetrically (polar
secondary adhesive). Uniform primary adhesive deposition, cell adhesion, and
photopolarization occurred simultaneously, and shortly thereafter, polar
secondary adhesive deposition occurred at the future growth site. Uniform primary
adhesive deposition and cell adhesion required secretion, but were independent of
filamentous-actin (F-actin) and microtubule function. Photopolarization of young
zygotes and polar secondary adhesive deposition required secretion but not
microtubules. F-actin served to localize secondary adhesive deposition at the
rhizoid pole; its function in polarization was more complex. F-actin was required
for axis selection; however, its role in realignment of an axis depended on the
light regime. The differing requirements for F-actin during development indicates
that the axis is not static, but changes with time. These findings indicate that
previous and future work on "axis formation" must be interpreted in the context
of the developmental stage of the zygote.
PMID- 9640332
TI - Differential dependency of unmyelinated and A delta epidermal and upper dermal
innervation on neurotrophins, trk receptors, and p75LNGFR.
AB - The impact of the nerve growth factor (NGF) family of neurotrophins and their
receptors was examined on the cutaneous innervation in the mystacial pads of
mice. Ten sets of unmyelinated and thinly myelinated sensory and autonomic
innervation were evaluated that terminated in the epidermis, upper dermis, and
upper part of the intervibrissal hair follicles. Mystacial pads were analyzed
from newborn to 4-week-old mice that had homozygous functional deletions of the
genes for NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3),
neurotrophin-4 (NT-4), tyrosine kinase (trk) A, trkB, trkC, or p75. Mystacial
pads were also analyzed in adult transgenic mice that had overproduction of NGF,
BDNF, or NT-3 driven by a keratin promoter gene. The innervation was revealed by
using immunofluorescence and immunocytochemistry with antibodies for protein gene
product (PGP) 9.5, calcitonin gene-related product (CGRP), substance P (SP),
galanin (GAL), neuropeptide Y (NPY), tyrosine hydroxylase (TH), and a
neurofilament protein. The cumulative results indicated that NGF/trkA signaling
plays a major role in the outgrowth and proliferation of sensory axons, whereas
NT-3/ trkA signaling plays a major role in the formation of sensory endings. TrkC
is also essential for the development of three sets of trkA-dependent sensory
innervation that coexpress CGRP, SP, and GAL. Another set of sensory innervation
that only coexpressed CGRP and SP was solely dependent upon NGF and trkA.
Surprisingly, most sets of trkA-dependent sensory innervation are suppressed by
trkB perhaps interacting with p75. BDNF and NT-4 appear to mediate this
suppressing effect in the upper dermis and NT-4 in the epidermis. In contrast to
sensory innervation, sympathetic innervation to the necks of intervibrissal hair
follicles depends upon NGF/trkA signaling interacting with p75 for both the axon
outgrowth and ending formation. Although NT-3/trkA signaling is essential for the
full complement of sympathetic neurons, NT-3 is detrimental to the formation of
sympathetic terminations to the necks of hair follicles. TrkB signaling mediated
by BDNF but not NT-4 also suppresses these sympathetic terminations. One sparse
set of innervation, perhaps parasympathetic, terminating at the necks of hair
follicles is dependent solely upon NT-3 and trkC. Taken together, our results
indicate that the innervation of the epidermis, upper dermis, and the upper
portion of hair follicles is regulated by a competitive balance between promoting
and suppressing effects of the various neurotrophins.
PMID- 9640333
TI - Stability and plasticity of neural crest patterning and branchial arch Hox code
after extensive cephalic crest rotation.
AB - The extent to which the spatial organisation of craniofacial development is due
to intrinsic properties of the neural crest is at present unclear. There is some
experimental evidence supporting the concept of a prepattern established within
crest while contiguous with the neural plate. In experiments in which the neural
tube and premigratory crest are relocated within the branchial region, crest
cells retain patterns of gene expression appropriate for their position of origin
after migration into the branchial arches, resulting in skeletal abnormalities.
But in apparent conflict with these findings, when crest is rerouted by late
deletion of adjacent crest, infilling crest alters its pattern of gene expression
to match its new location, and a normal facial skeleton results. In order to
reconcile these findings thus identify processes of relevance to the course of
normal development, we have performed a series of neural tube and crest rotations
producing a more extensive reorganisation of cephalic crest than has been
previously described. Lineage analysis using DiI labelling of crest derived from
the rotated hindbrain reveals that crest does not migrate into the branchial arch
it would have colonised in normal development, rather it simply populates the
nearest available branchial arches. We also find that crest adjacent to the
grafted region contributes to a greater number of branchial arches than it would
in normal development, resulting in branchial arches containing mixed cell
populations not occurring in normal development. We find that after exchange of
first and third arch crest by rotation of r1-7, crest alters its expression of
hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the
reestablishment of the normal branchial arch Hox code. A facial skeleton in which
all the normal components are present, with some additional ectopic first arch
structures, is formed in this situation. In contrast, when second and third arch
crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is
stable, resulting in the persistence of an abnormal branchial arch Hox code and
extensive defects in the hyoid skeleton. We suggest that the intrinsic properties
of crest have an effect on the spatial organisation of structures derived from
the branchial arches, but that exposure to increasingly novel environments within
the branchial region or "community effects" within mixed populations of cells can
result in alterations to crest Hox code and morphogenetic fate. In both classes
of operation we find that there is a tight link between the resulting branchial
arch Hox code and a particular skeletal morphology.
PMID- 9640334
TI - FGF is an essential regulator of the fifth cell division in preimplantation mouse
embryos.
AB - Fibroblast growth factor (FGF) signaling is required prior to gastrulation in the
mouse embryo. To test for the spatial and temporal requirements of FGF signaling,
a dominant negative FGF receptor (dnFGFR) was used to make transgenic mouse
embryos. In mosaic embryos, cell division ceased at the fifth cell division in
all cells that expressed the mutant receptor, but cell death did not increase.
After the fifth cell division, the progeny of unaltered cells and cells
expressing lacZ continued to accumulate at the same rate, suggesting that the FGF
requirement is cell autonomous. In mosaic embryos, lacZ, but not dnFGFR
expression was detected in mitotic trophoblasts adjacent to the ICM. Conversely,
dnFGFR-expressing extraembryonic ectoderm cells were detected at the abembryonic
pole in postmitotic cells. In blastocysts expressing the dnFGFR in all cells, the
morphology appeared normal and inner cell masses (ICMs) formed, but resultant
embryos had only one-third the number of cells as control embryos. In these
blastocysts, cell division had also ceased at the fifth cell division, but
cavitation, a concurrent morphogenetic event, initiated and progressed normally.
To test for the continuing requirement of FGF, FGFR-3 was overexpressed in all
cells and resulted in an increase in cell numbers after the fifth cell cycle. In
a model for postimplantation development, addition of FGF-4 to blastocyst
outgrowths increased the number of extraembryonic ectoderm cells, suggesting a
continuing role for FGF. Thus, FGF signaling induces the cell division of
embryonic and extraembryonic cells in the preimplantation mouse embryo starting
at the fifth cell division. The signal requirement for FGF is cell autonomous,
but is not required to prevent cell death. This provides the first evidence for
the necessity of a growth factor before implantation.
PMID- 9640335
TI - Evidence that Gq family G proteins do not function in mouse egg activation at
fertilization.
AB - Embryonic development is initiated after the fertilizing sperm contacts the egg
and triggers a process termed "egg activation," resulting in calcium release,
cortical granule exocytosis, recruitment of maternal mRNAs, and cell cycle
resumption. Heterotrimeric guanine nucleotide-binding proteins (G proteins) may
be involved in mouse egg activation since inhibition of G protein beta gamma
subunits partially inhibits sperm-induced cell cycle resumption. In addition,
specific events of egg activation can be initiated in the absence of sperm by
acetylcholine stimulation of mouse eggs overexpressing the human m1 muscarinic
receptor, a G protein-coupled receptor. In somatic cell, G proteins in the Gq
family couple ligand stimulation of the m1 muscarinic receptor to activation of
phospholipase C, resulting in the production of inositol 1,4,5-trisphosphate
(IP3) and IP3-mediated release of intracellular calcium. Since IP3-mediated
calcium release is involved in egg activation at fertilization, we have examined
the role of Gq family G proteins in both sperm-independent (muscarinic receptor
mediated) and sperm-induced egg activation using a function-blocking antibody
raised against the common C-terminal region of Gq and G11 proteins. We show that
this antibody effectively inhibits Gq family G proteins in mouse eggs by
demonstrating that the antibody inhibits egg activation in response to
stimulation of the m1 muscarinic receptor. This same antibody, however, does not
inhibit sperm-induced egg activation events. These results indicate that although
activation of Gq family G proteins can result in egg activation in the mouse, it
is unlikely that these proteins are used by the sperm to initiate egg activation
at fertilization.
PMID- 9640336
TI - Syncope and sudden death in hypertrophic cardiomyopathy.
PMID- 9640337
TI - Preventing adult disease: windows of opportunity.
PMID- 9640338
TI - Reflex responses of venous capacitance vessels in patients with hypertrophic
cardiomyopathy.
AB - 1. The aim of this study was to determine if there is impaired reflex
venoconstriction in patients with hypertrophic cardiomyopathy and whether this is
related to a history of syncope or exercise hypotension. 2. Thirty percent of
patients with hypertrophic cardiomyopathy have exercise-induced hypotension
associated with a failure of arteriolar constriction. Impaired venoconstriction
could exacerbate this situation. 3. We evaluated 43 patients with hypertrophic
cardiomyopathy and 24 controls. Nuclear venous plethysmography was used to
measure forearm venous capacitance during lower body negative pressure, splenic
venous volume changes during bicycle exercise and blood pressure responses to
treadmill exercise. We assessed any association between abnormal reflex venous
control and a history of syncope and exercise hypotension. 4. The percentage
reduction in unstressed forearm venous volume during lower body negative pressure
was similar in patients and controls (8.9 +/- 7.1% versus 9.7 +/- 5.9%, P not
significant). Patients with a history of syncope demonstrated a less marked
percentage reduction in volume than those without (-2.1 +/- 6.9% versus -10.6 +/-
6.0%, P = 0.001). In three patients with a history of syncope there was a
paradoxical increase in forearm venous volume during lower body negative
pressure. During exercise there was a substantially smaller decrease in splenic
venous volume in patients compared with controls (-20.1 +/- 14.0% and -42.6 +/-
12.6% respectively, P = 0.0001). Furthermore, there was an association between
attenuated splenic venoconstriction or venodilation and exercise hypotension in
patients (P = 0.005). 5. Abnormal reflex control of venous capacitance beds in
patients with hypertrophic cardiomyopathy was associated with both syncope and
exercise hypotension.
PMID- 9640339
TI - Dynamics of circulatory adjustments to head-up tilt and tilt-back in healthy and
sympathetically denervated subjects.
AB - 1. The initial circulatory adjustments induced by head-up tilt and tilt-back were
investigated in six healthy subject (aged 30-58 years) and six patients with
orthostatic hypotension due to pure autonomic failure (aged 33-65 years). 2.
Continuous responses of finger arterial pressure and heart rate were recorded by
Finapres. A pulse contour algorithm applied to the arterial pressure waveform was
used to compute stroke volume responses. 3. In the healthy subjects, head-up tilt
induced gradual circulatory adjustments. After 1 min upright stroke volume and
cardiac output had decreased by 39 +/- 9% and 26 +/- 10% respectively. Little
change in mean blood pressure at heart level (+1 +/- 7 mmHg) indicated that
systemic vascular resistance had increased by 39 +/- 24%. The gradual responses
to head-up tilt contrasted with the pronounced and rapid circulatory responses
upon tiltback. After 2-3 s a rapid increase in stroke volume (from 62 +/- 8% to
106 +/- 10%) and cardiac output (from 81 +/- 11% to 118 +/- 20%) was observed
with an overshoot of mean arterial pressure above supine control values of 16 +/-
3 mmHg at 7 s. In the patients a progressive fall in blood pressure on head-up
tilt was observed. After 1 min upright mean blood pressure had decreased by 59 +/
8 mmHg. No change in systemic vascular resistance and a larger decrease in
stroke volume (60 +/- 7%) and cardiac output (53 +/- 8%) were found. On tilt-back
a gradual recovery of blood pressure was observed. 4. In healthy humans upon head
up tilt neural compensatory mechanisms are very effective in maintaining arterial
pressure at heart level. The gradual circulatory adjustments to head-up tilt in
healthy subjects contrast with the pronounced and abrupt circulatory changes on
tilt-back. In patients with a lack of neural circulatory reflex adjustments,
gradual blood pressure decreases to head-up tilt and gradual increases to tilt
back are observed.
PMID- 9640340
TI - Cerebral blood flow velocity during and after sustained isometric skeletal muscle
contractions in man.
AB - 1. Twenty-seven young subjects used their right hand to perform sustained,
isometric contractions at 40% of maximum for 2 min while lying supine. 2. During
the last 30 s of exercise, mean arterial blood pressure increased by 38 +/- 4
mmHg (mean +/- S.E.M.) and heart rate by 27 +/- 2 beats/min. 3. Nineteen of the
subjects respired eucapnically during exercise, increasing ventilation by 4.1 +/-
0.5 litres/min. Eight subjects hyperventilated (7.1-19.6 litres/min) and
decreased end-tidal PCO2 by 8.2 to 15.1 mmHg during the last minute of exercise.
4. In the eucapnic subjects mean flow velocity in the right (i.e. contralateral
to the activated cortex) middle cerebral artery increased by 11.4 +/- 1.0 cm/s, a
change of 17%, during the contraction. This represents an increase in volume flow
to the territory of this vessel, but an increase in global flow to the brain
cannot be inferred. 5. In the eight subjects who hyperventilated during exercise,
there was no rise of flow velocity in the middle cerebral artery, and in some
subjects there was a fall during the first 2 min of recovery. These findings
suggest that if subjects hyperventilate during handgrip exercise there could be a
fall in volume flow to many regions of the brain during and after the exercise.
PMID- 9640341
TI - Differential regulation of ventricular adrenomedullin and atrial natriuretic
peptide gene expression in pressure and volume overload in the rat.
AB - 1. Adrenomedullin is a recently discovered vasodilating and natriuretic peptide
whose physiological and pathophysiological roles remain to be established. Like
atrial natiuretic peptide adrenomedullin is expressed in the left ventricle.
Ventricular expression of atrial natriuretic peptide is known to be markedly
increased by volume or pressure overload. In this study we investigated whether
ventricular expression of adrenomedullin is similarly stimulated under such
conditions. 2. Ventricular adrenomedullin and atrial natriuretic peptide mRNA
levels as well as those of a loading control mRNA (glyceraldehyde-3-phosphate
dehydrogenase) were quantified by Northern blot analysis in (a) rats with severe
post-infarction heart failure induced by left coronary ligation at 30 days post
surgery and (b) in rats with pressure-related cardiac hypertrophy induced by
aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days)
after surgery. Levels were compared with those in matched sham-operated controls.
3. The mRNA level of atrial natriuretic peptide was markedly increased (8-10
fold) in the left ventricle of animals with post-infarction heart failure. In
contrast, there was only a modest (40%) increase in the level of adrenomedullin
mRNA. In rats with pressure-induced cardiac hypertrophy the ventricular level of
atrial natriuretic peptide mRNA was again markedly increased (maximum 10-fold).
The increase was first noticeable at 24 h post-banding and persisted until 28
days. In contrast, there was no change in adrenomedullin mRNA level compared with
sham-operated rats at any time point. 4. Despite having similar systemic effects,
the expression of adrenomedullin and atrial natriuretic peptide in the left
ventricle is differently regulated. The findings imply distinct roles for the two
peptides. The results do not support an important role for ventricular
adrenomedullin expression in the remodelling process that occurs during the
development of cardiac hypertrophy but suggest that ventricular adrenomedullin
participates in the local and/or systemic response to heart failure.
PMID- 9640342
TI - Chronic administration of octreotide ameliorates portal hypertension and portal
hypertensive gastropathy in rats with cirrhosis.
AB - 1. Portal hypertension and hyperdynamic circulation have been postulated to play
a role in the pathogenesis of portal hypertensive gastropathy. Administration of
octreotide to portal hypertensive rats has been shown to reduce portal pressure
and ameliorate hyperdynamic circulation. 2. This study investigated the effects
of chronic administration of octreotide on systemic and portal haemodynamics and
the development of portal hypertensive gastropathy in carbon tetrachloride
induced cirrhotic rats. 3. After 12 weeks of carbon tetrachloride induction,
cirrhotic rats were randomly assigned to receive either placebo (5% dextrose in
water) or octreotide (65 micrograms/kg in 5% dextrose in water) subcutaneously
twice daily for 10 days. Haemodynamic studies with a thermodilution technique and
gastric morphometric analyses were performed at 10 days after treatment. 4. In
cirrhotic rats, octreotide treatment induced a significant increase in systemic
vascular resistance (2.7 +/- 0.2 versus 3.4 +/- 0.2 mmHg/ml.min-1.100 g-1, P <
0.05) and decrease in portal pressure (12.5 +/- 1.2 versus 9.9 +/- 0.5 mmHg, P <
0.05) compared with placebo-treated rats. In addition, octreotide treatment
significantly reduced the mean cross-sectional area of gastric mucosal vessels
(2290 +/- 145 versus 1810 +/- 101 micron 2, P < 0.05). 5. This study shows that
chronic octreotide treatment ameliorates the development of portal hypertensive
gastropathy in cirrhotic rats. The effect of octreotide on portal hypertensive
gastropathy may, at least partly, be due to the alleviation of portal
hypertension and hyperdynamic circulation.
PMID- 9640343
TI - Early administration of angiotensin-converting enzyme inhibitor captopril,
prevents the development of hypertension programmed by intrauterine exposure to a
maternal low-protein diet in the rat.
AB - 1. Associations of intrauterine exposure to maternal undernutrition with later
hypertension and coronary heart disease in the human population have been
duplicated in the rat. Fetal exposure to low protein diets produces offspring
that develop raised systolic blood pressure by the age of weaning. This animal
model of 'programmed' hypertension was used to investigate the role of the renin
angiotensin system in the initiation and maintenance of high blood pressure. 2.
Pregnant rats were fed diets containing 18 or 9% casein from conception until
littering. The offspring from these pregnancies were administered captopril
either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The
feeding of low protein diets in pregnancy had no effect upon the reproductive
ability of female rats and the offspring generated were of normal birthweight. By
4 weeks of age the male and female offspring of low-protein-fed dams had systolic
blood pressures that were 24-25 mmHg higher than those of rats exposed to a
control diet in utero. 4. Treatment of 10-week-old female offspring with
captopril for 2 weeks indicated that angiotensin II formation may play a role in
the maintenance of high blood pressure in low-protein-exposed rats. While
captopril had no significant effect upon systolic pressures of rats exposed to
the control diet in intrauterine life, the systolic blood pressures of low
protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to
male and female offspring between 2 and 4 weeks of age exerted long-term effects
upon systolic blood pressure. Eight weeks after cessation of treatment, at an age
where maximal blood pressures are achieved, captopril-treated, low-protein
exposed rats had similar blood pressures to normotensive rats exposed to the
protein-replete diet in utero. 6. In conclusion, we have demonstrated that the
elevation of adult blood pressure associated with fetal exposure to a maternal
low-protein diet, is prevented by early administration of an angiotensin
converting enzyme inhibitor. The actions of angiotensin II in the late suckling
period may be a critical determinant of long-term cardiovascular functions in
these animals.
PMID- 9640344
TI - Human muscle sympathetic activity and cardiac catecholamine spillover: no support
for augmented sympathetic noradrenaline release by adrenaline co-transmission.
AB - 1. Evidence from animal studies indicates that circulating adrenaline may be
taken up into sympathetic nerves, facilitating the release of noradrenaline. To
test whether adrenaline acts as a co-transmitter in humans we studied eight
healthy men (aged 19-23 years) during isometric handgrip before and after an
adrenaline infusion (1-3 micrograms/min for > 30 min). Sympathetic activity was
assessed using radiotracer kinetic techniques to measure total and cardiac
spillovers of noradrenaline and adrenaline, and microneurography to measure
muscle sympathetic activity. 2. During the adrenaline infusion systolic blood
pressure and heart rate increased significantly and diastolic blood pressure
decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma
noradrenaline concentrations, increased significantly. Muscle sympathetic nerve
traffic increased both during and after the end of the infusion. 3. Thirty
minutes after the end of the adrenaline infusion there was adrenaline release
from the heart (1.5 +/- 0.4 ng/min, mean +/- S.E.M.) indicating that significant
adrenaline loading of cardiac sympathetic nerves had occurred. At this time
muscle sympathetic nerve traffic and total body and cardiac noradrenaline
spillovers were similar (P > 0.05) to pre-adrenaline infusion values (nerve
traffic 24 +/- 4 versus 21 +/- 3 bursts/min; total noradrenaline spillover 698 +/
98 versus 618 +/- 119 ng/min; cardiac noradrenaline spillover 16.2 +/- 2.8
versus 13.9 +/- 3.9 ng/min). 4. Isometric handgrip contraction evoked similar
responses pre- and post-adrenaline infusion in total and cardiac noradrenaline
spillovers and in muscle sympathetic activity. 5. The results do not support the
theory that adrenaline is a co-transmitter facilitating noradrenaline release
from human sympathetic nerves.
PMID- 9640345
TI - Vascular endothelial growth factor (VEGF) is released from platelets during blood
clotting: implications for measurement of circulating VEGF levels in clinical
disease.
AB - 1. Dysregulated vascular endothelial growth factor (VEGF) expression has been
reported in several pathological states based upon evidence of elevated serum
VEGF levels. Using two immunoassays for VEGF, this study determines normal plasma
and serum VEGF ranges, determines which are more likely to reflect circulating
VEGF levels and investigates a potential contribution of VEGF from platelets to
VEGF levels detected in serum. 2. The presence of soluble VEGF receptor, sflt-1,
at a molar excess of 7:1 significantly reduced measured VEGF levels in both
assays. Serum VEGF levels were higher than plasma levels in children [(mean +/-
S.E.M.) 306.1 +/- 39.4 versus 107.4 +/- 24.9 pg/ml, P < 0.0001] and adults (249.4
+/- 46.4 versus 76.1 +/- 10.7 pg/ml, P < 0.0001). Serum VEGF increased with
clotting time (P = 0.0005 t0 compared with 2 h samples); plasma VEGF levels were
not affected by time between sampling and centrifugation. 3. Calcium-induced
clotting of platelet-rich but not platelet-poor plasma induced VEGF release with
a proportional response between platelet count and VEGF level and isolated
platelets released significant quantities of VEGF upon incubation with thrombin.
Reverse transcriptase-PCR studies confirmed that platelets express VEGF121 and
VEGF165 mRNA. 4. These data suggest that plasma is the preferred medium to
measure VEGF levels; a significant and highly variable platelet-mediated
secretion of VEGF during the clotting process invalidates the use of serum as an
indicator of circulating VEGF levels in disease states.
PMID- 9640346
TI - Bone mineral changes during pregnancy and lactation: a longitudinal cohort study.
AB - 1. The influence of pregnancy, lactation and weaning on bone mineral density in
healthy women was investigated during a 2 year prospective study of 59 pregnant
and lactating women from the 18th week of gestation. 2. Bone mineral density was
measured by dual energy X-ray absorptiometry at the non-dominant radius ultra
distally and more proximally in the 18th and 37th weeks of gestation, and 0, 3,
6, 12 and 18 months after delivery. Measurements of bone mineral density of the
lumbar spine, the proximal femur and the whole body were performed at all dates
after delivery. 3. Reappearance of menstruation after delivery averaged 6.1
months; mean lactating period was 8.7 months. During pregnancy and lactation bone
mineral density tended to decrease, but different measuring sites showed
different patterns of bone mineral density changes. The reduction in the ultra
distal radius during pregnancy amounted to 2%, and no further changes were
observed here during lactation. After delivery, reduction in mean bone mineral
density was most pronounced in the spine (5.2% in 3 months), but the fall in bone
mass tended to revert after resumption of menstruation. Bone mineral density was
still reduced by 3.3% after 12 months in women with menstruation resumption later
than 8 months after delivery. No significant reduction was observed 18 months
after delivery. No association with calcium intake, weight changes or initial
bone mineral density was observed. High calcium intake did not protect against
bone mineral loss in the spine and the femur. 4. Thus it can be concluded that
bone loss during pregnancy and lactation took place mainly from the trabecular
skeleton. Resumption of menstruation tended to result in a regain of bone mass
towards baseline.
PMID- 9640347
TI - Sustained modifications of protein metabolism in various tissues in a rat model
of long-lasting sepsis.
AB - 1. Sepsis was induced in rats by an intravenous injection of live bacteria.
Infected and pair-fed animals were studied before the infection, in an acute
septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a
late septic phase (day 10). Protein synthesis rates were measured in vivo after
administration of a flooding dose of L[1-13C]valine. 2. During the acute phase,
muscle protein loss associated with infection resulted from both a decrease in
protein synthesis and an increase in proteolysis. During the chronic phase and
the late phase, the increase of proteolysis in infected rats as compared with
pair-fed animals persisted, worsening muscle atrophy. Skin protein synthesis
rates were not significantly modified by infection. However, skin protein content
decreased 6 and 10 days after infection, suggesting an increased proteolysis in
response to sepsis. 3. Protein synthesis in liver of infected rats was twice that
of pair-fed animals. Liver protein synthesis remained elevated in infected rats
compared with pair-fed animals until day 10. Hypoalbuminaemia and high plasma
concentrations of fibrinogen were evident at all periods studied. alpha 2
Macroglobulin and alpha 1-acid glycoprotein reached peak concentrations during
the acute phase (concentrations increased 50 times in infected rats). On day 10,
the levels of these proteins were still about 12-fold higher. 4. Protein
synthesis rates were significantly increased in the digestive tract and lung of
infected rats compared with pair-fed groups on days 2 and 6, but were similar in
the two groups on day 10 post-infection. The fractional protein synthesis rate
was increased 3-fold over the entire experimental period in the spleen. 5. The
results show that sepsis stimulates protein synthesis in various tissues over a
long time, and that skin, like muscle, can provide amino acids to the rest of the
body.
PMID- 9640348
TI - Proximal renal tubular peptide catabolism, ammonia excretion and tubular injury
in patients with proteinuria: before and after lisinopril.
AB - 1. Progression to renal failure may be linked to the degree of proteinuria
through tubulo-interstitial mechanisms. However, there are no data in man on the
kinetics of proximal renal tubular protein catabolism or markers of tubular
injury before and after lisinopril. We developed a method to allow such studies,
and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in
patients with nephrotic range proteinuria which was associated with increased
ammonia excretion. 2. In this study, 10 patients with mild renal impairment (51Cr
EDTA clearance 63.7 +/- 8.3 ml.min-1.1.73 m-2) and heavy proteinuria (8.2 +/- 2.3
g/ 24 h) were given lisinopril (10-20 mg) for 6 weeks. Renal tubular catabolism
of intravenous aprotinin was measured before and after lisinopril by renal
imaging and urinary excretion of the free radiolabel over 26 h. Fractional
degradation was calculated from these data. Fresh timed urine collections were
also analysed for ammonia excretion every fortnight from 6 weeks before
treatment. Total urinary N-acetyl-beta-D-glucosaminidase and the more tubulo
specific N-acetyl-beta-D-glucosaminidase 'A2' isoenzyme were also measured. 3.
After lisinopril proteinuria fell significantly as expected (from 9.5 +/- 1.6 to
4.5 +/- 1.0 g/24 h, P < 0.01). This was associated with a reduction in metabolism
over 26 h (from 1.7 +/- 0.1 to 1.2 +/- 0.1% dose/h, P < 0.01) and in fractional
degradation of aprotinin (from 0.08 +/- 0.02 to 0.04 +/- 0.007/h, P < 0.04).
Ammonia excretion also fell significantly (from 1.2 +/- 0.1 to 0.6 +/- 0.1
mmol/h, P < 0.0001), as did both total urinary N-acetyl-beta-D-glucosaminidase (P
< 0.0001) and the N-acetyl-beta-D-glucosaminidase 'A2' isoenzyme (P < 0.015).
These observations after lisinopril treatment have not been described previously.
There was no significant change in blood pressure nor in glomerular
haemodynamics.
PMID- 9640349
TI - Inappropriately high plasma leptin levels in obese haemodialysis patients can be
reduced by high flux haemodialysis and haemodiafiltration.
AB - 1. Blood leptin levels are increased in obese subjects and seem to play a major
role in the hypothalamic regulation of appetite and energy expenditure. 2. We
measured plasma leptin levels in a cohort of 46 patients on maintenance
haemodialysis treatment and 26 control subjects. 3. Higher body mass indices were
associated with higher plasma leptin levels in both groups. 4. The increase was
more pronounced in the dialysis group than in the control group (P = 0.001),
leading to inappropriately high plasma levels. 5. Haemodialysis with low flux
cellulosic dialysers did not result in a decrease in plasma levels, while
dialysis with high flux dialysers and haemodiafiltration led to a substantial
reduction of the initial value to 76.95 +/- 14.89% (P = 0.013) and 62.90 +/-
24.94% (P = 0.001) respectively. 6. Our data suggest that high flux dialysis
membranes can decrease plasma leptin levels and that inappropriately high plasma
leptin levels may play a role in the nutrition of haemodialysis patients.
PMID- 9640350
TI - Neutrophil cathepsin G modulates platelet P-selectin expression and inhibits P
selectin-mediated platelet-neutrophil adhesion.
AB - 1. Close contact between platelets and neutrophils modulates their cellular
interactions in thrombotic and inflammatory states, with stimulation of P
selectin expression on platelets by agonists such as thrombin and neutrophil
derived cathepsin G being critical in mediating platelet-neutrophil adhesion.
This study compared the effects of thrombin and cathepsin G on platelet P
selectin expression and on P-selectin-mediated platelet-neutrophil adhesion. 2.
Washed platelets and platelet-neutrophil mixed cell suspensions
(platelet/neutrophil ratio, 10:1) were incubated with either the supernatant of
activated neutrophils, purified cathepsin G or thrombin. Platelet P-selectin
expression and platelet adhesion to neutrophils was quantified by flow
fluorocytometric analysis. 3. The supernatant from activated neutrophils
stimulated platelet P-selectin expression comparable to that produced by purified
cathepsin G or thrombin. P-selectin expression induced by both activated
neutrophil supernatant and purified cathepsin G was completely inhibited by alpha
1-antichymotrypsin, a specific inhibitor of cathepsin G. Unlike thrombin, which
induced maximum platelet P-selectin expression by 10 min, sustained to 120 min,
cathepsin G induced an initial large increase in platelet P-selectin expression,
followed by a progressive reduction over 30-60 min to baseline levels. 4. Co
incubation of neutrophils with thrombin-stimulated platelets resulted in a
significant increase in P-selectin-mediated platelet-neutrophil adhesion, which
was completely inhibited by preincubation of neutrophils with anti-sialyl
Lewis(x) monoclonal antibody. Thrombin produced maximum platelet-neutrophil
adhesion by 10 min which remained stable over 120 min. In contrast, cathepsin G
stimulated platelets did not adhere to neutrophils over 120 min of co-incubation.
Addition of cathepsin G to thrombin-stimulated platelets caused a progressive
reduction over 30-60 min to baseline levels of platelet-neutrophil adhesion. 5.
Neutrophil-derived cathepsin G is a potent platelet activator, but unlike
thrombin it causes a time-dependent loss of platelet P-selectin expression and
inhibits P-selectin-mediated platelet-neutrophil adhesion. Therefore, cathepsin G
may modulate thrombin-mediated platelet-neutrophil adhesive interactions in
inflammation and thrombosis.
PMID- 9640351
TI - Effect of oxidative stress on lymphocytes from elderly subjects.
AB - 1. Oxidative damage has been associated with ageing, but there is no agreement as
to whether or not it is produced by a decrease in antioxidant defences with the
ageing process. In purified lymphocytes from 47 healthy elderly (75.27 +/- 0.91
years) and 47 healthy young (29.87 +/- 0.53 years) volunteers, we studied the
levels of antioxidant enzyme activity (superoxide dismutase, catalase and
glutathione peroxidase), protein oxidative damage (as protein carbonyl content)
and lysosomal proteolytic activity (cathepsins B, H and L), with and without
exposure to oxidative stress produced by 25 mumol/l H2O2. 2. There were no
differences in antioxidant enzyme activities in the stressed and non-stressed
samples between the young and elderly subjects, indicating that there was no
relationship between age and antioxidant enzyme activity even in oxidative
stress. However, a dissimilar response to oxidative stress was observed in
protein oxidative damage and cathepsin B and L activities, depending on the age
of the donor. 3. With these results we conclude that oxidative stress produces
greater protein oxidative damage and increased protein degradation in elderly
subjects than in young ones; this effect cannot be attributed to dissimilar
antioxidant enzyme responses to oxidative stress, since these did not differ
between the two age groups.
PMID- 9640352
TI - Time course and pattern of pulmonary flow distribution following unilateral
airway occlusion in sheep.
AB - 1. Unilateral bronchial occlusion causes ipsilateral hypoxic pulmonary
vasoconstriction, which shifts blood flow towards the other lung. We studied the
time course of flow diversion following acute bronchial occlusion, and the
temporal effect of the latter on blood gases and vertical distribution of blood
flow within the two lungs. 2. Serial infusion of radioactive or fluorescent
microspheres were given to each of seven adult standing sheep before, during
occlusion of the left mainstem bronchus for up to 6 min, and after release of
occlusion. Pulmonary and systemic arterial pressures were recorded continuously
and arterial and mixed venous blood gases were determined intermittently. Post
mortem, the lungs were inflated, dried and cut into slices. Relative blood flow
at the time of infusion was expressed as the weight-normalized intensity of each
tracer in each slice or lung divided by the weight-normalized intensity in the
two lungs. 3. Within 30 s, 1 min and 2 min after onset of occlusion, flow in the
occluded lung had decreased to 68-84% (range), 51-78% and 43-79% respectively, of
the initial value. In the contralateral lung, flow increased by 10-24%, 14-37%
and 23-39% respectively. The distribution of flow along the gravitational axis
within each lung varied widely between animals, both before and during occlusion.
The during-occlusion profiles in the occluded lung differed from those in the non
occluded lung. In either lung, during-occlusion profiles could not be predicted
with certainty from the pre-occlusion profiles. Two minutes post-occlusion, inter
and intra-lung flow distribution were nearly the same as before occlusion.
Arterial oxygen tension fell in the first minute of occlusion, but never below
7.5 kPa, and increased slowly thereafter. Arterial carbon dioxide tension
increased slightly throughout the occlusion period. No appreciable changes in
systemic or pulmonary artery pressure were observed. Post-occlusion, arterial
oxygen tension was still sub-normal, while carbon dioxide tension continued to
increase. 4. We conclude that acute unilateral bronchial occlusion diverts blood
flow within 30 s towards the contralateral lung. This rapidly occurring flow
diversion prevents the development of severe arterial hypoxaemia. The variable
and largely unpredictable distribution of blood flow in the hyperfused non
occluded lung might explain some of the gas-exchange abnormalities observed in
physiologically hyperfused lungs and in patients with one hyperfused lung.
PMID- 9640353
TI - Benjamin W. Zweifach 1910-1997.
PMID- 9640354
TI - Linear viscoelastic properties of bovine brain tissue in shear.
AB - We report the results from a series of rheological tests of fresh bovine brain
tissue. Using a standard Bohlin VOR shear rheometer, shear relaxation and
oscillating strain sweep experiments were performed on disks of brain tissue 30
mm in diameter, with a thickness of 1.5-2 mm. The strain sweep experiment showed
that the viscoelastic strain limit is of the order of 0.1% strain. Shear
relaxation data do not indicate the presence of a long-term elastic modulus,
indicating fluid-like behavior. A relaxation spectrum was calculated by inverting
the experimental data and used to predict oscillatory response, which agreed well
with measured data.
PMID- 9640355
TI - Rheological behavior of rat mesangial cells during swelling in vitro.
AB - The response of cells to mechanical forces depends on the rheological properties
of their membranes and cytoplasm. To characterize those properties, mechanical
and electrical responses to swelling were measured in rat mesangial cells (MC)
using electrophysiologic and video microscopic techniques. Ion transport rates
during hyposmotic exposures were measured with whole-cell recording electrodes.
Results showed that cell swelling varied nonlinearly with positive internal
pressure, consistent with a viscoelastic cytoplasm. The extrapolated area
expansivity modulus for small deformations was estimated to be 450 dyne/cm. Cell
swelling, caused either by positive pipet pressure or hyposmotic exposure (40-60
mOsm Kg-1), rapidly induced an outwardly rectifying membrane conductance with an
outward magnitude 4-5 times the baseline conductance of 0.9 +/- 0.5 nS (p < .01).
Swelling-induced (SI) current was weakly selective for K+ over Na+, partially
reversed upon return to isotonicity, and was antagonized by 0.5 mM GdCl3 (p <
0.02; n = 6). Isolated cells treated with GdCl3 rapidly lysed after hypotonic
exposure, in contrast to untreated cells that exhibited regulatory volume
decrease (RVD). Our results indicate that volume regulation by MC depends upon a
large swelling-induced K+ efflux, and suggest that swelling in MC is a
viscoelastic process, with a viscosity dependent on the degree of swelling.
PMID- 9640356
TI - Inertial migration based concentration factors for suspensions of Chlorella
microalgae in branched tubes.
AB - When a dilute suspension flows in the laminar regime through a tube, under
certain conditions the suspended particles migrate radially to an equilibrium
radial position. Branched tubes can use this radial concentration distribution to
concentrate dilute suspensions. Suspensions of microalgae, Chlorella vulgaris,
were pumped through tubes of various diameters for tube Reynolds number ranging
from 47-1839 and photographed. Upstream particle concentration profiles were
obtained by image analysis of the photographs. The dividing stream surfaces in
branched tubes were obtained from the three-dimensional numerical solutions of
the Navier-Stokes equations for steady, laminar, and homogeneous flow through
tubes having one and two orthogonal branches. Concentration factors for Chlorella
suspensions in branched tubes, predicted by a general method, fall in the range
of 1.0-1.3.
PMID- 9640357
TI - Simulation of red blood cell aggregation in shear flow.
AB - A simulation model has been developed for red blood cell (RBC) aggregation in
shear flow. It is based on a description of the collision rates of RBC, the
probability of particles sticking together, and the breakage of aggregates by
shear forces. The influence of shear rate, hematocrit, aggregate fractal
dimension, and binding strength on aggregation kinetics were investigated and
compared to other theoretical and experimental results. The model was used to
simulate blood flow in a long large diameter tube under steady flow conditions at
low Reynolds numbers. The time and spatial distribution of the state of
aggregation are shown to be in qualitative agreement with previous B-mode
ultrasound studies in which a central region of low echogenicity was noted. It is
suggested that the model can provide a basis for interpreting prior measurements
of ultrasound echogenicity and may help relate them to the local state of
aggregation.
PMID- 9640358
TI - Ultrasound backscattering from non-aggregating and aggregating erythrocytes--a
review.
AB - The objective of the present paper is to provide a detailed review of
theoretical, experimental and clinical works aimed at understanding the
scattering of ultrasound by red blood cells (RBC). The paper focuses on the role
of biofluid mechanics and blood biorheology on the scattering mechanisms. The
influence of RBC aggregation on the ultrasound backscattered power is
specifically addressed. After a short introduction, the paper presents the theory
of Rayleigh scattering and summarizes theoretical models on ultrasound
backscattering by RBC. The particle, continuum and hybrid models are presented
along with reported packing factors used to consider the orderliness in the
spatial arrangement of RBC. Computer models of ultrasound backscattering by RBC
are also presented in this section. In the second section, experimental factors
affecting the ultrasound backscattered power from blood are presented. The
influence of the volume of the scatterers, ultrasound frequency, hematocrit,
orientation of the scatterers, flow turbulence, flow pulsatility, and
concentration of fibrinogen and dextran is discussed. The third section focuses
on the use of ultrasound to characterize RBC aggregation. Three aspects are
reported: the shear rate dependence of the backscattered power, the "black hole"
phenomenon, and the kinetics of RBC rouleau formation. The fourth section reports
in vivo observations of the "smoke like" echo in mitral valve disease, and blood
echogenicity and backscattered power in veins and arteries. In the last section,
new areas of research, clinical applications of ultrasound backscattering, and
areas of potential future developments are presented.
PMID- 9640359
TI - Vulval lichen planus.
AB - Lichen planus of the vulva can occur as part of more widespread disease or in
isolation. Its cause is unknown, but it can become chronic and has a potential
for malignant change. It may present a difficult management problem and several
treatments have been used with variable success. This review focuses on the
problem of vulval lichen planus, and highlights some of the treatments and
management strategies that have been used to date.
PMID- 9640360
TI - Identification of common dermatophytes (Trichophyton, Microsporum,
Epidermophyton) using polymerase chain reactions.
AB - Polymerase chain reaction (PCR) fingerprinting detected DNA polymorphisms among
frequently isolated species and strains of the genera Trichophyton, Microsporum
and Epidermophyton. The patterns generated by this DNA-based method permitted
species and strains to be identified. The conventional methods to identify
dermatophytes rely on the expression of characteristic morphological features, as
well as several physiological properties. Identification is often delayed or
problematic because isolates may be slow to form conidia or produce atypical
microscopic structures or colony appearances. Using non-specific primers such as
(AC)10, (GTG)5, M13 core sequence and AP3, characteristic PCR profiles were
generated for 17 species. Intraspecies variables were also observed for four of
six varieties of T. mentagrophytes, whereas no detectable DNA variability was
found within the three varieties of T. tonsurans. Comparing species-specific PCR
fingerprints of clinical isolates with those of type strains, species could be
identified by their PCR fingerprints, even if they could not be identified by the
accepted phenotypic characteristics.
PMID- 9640361
TI - Non-uniform cellular packing of the stratum corneum and permeability barrier
function of intact skin: a high-resolution confocal laser scanning microscopy
study using highly deformable vesicles (Transfersomes).
AB - Novel, functional skin staining with fluorescent, ultradeformable lipid vesicles
(Transfersomes, IDEA, Munich, Germany) was developed and combined with confocal
laser scanning microscopy. This revealed the structural and barrier
characteristics of intact skin to a resolution of > or = 0.2 micron, that is, to
the limit of light microscopy. Different routes of penetration into the stratum
corneum were visualized and new details in the skin anatomy and barrier were
unveiled. Most prominent was the lateral inhomogeneity of the stratum corneum,
where three to 10 neighbouring corneocyte 'columns' were found to form a cluster.
Corneocyte edges inside each cluster intercalated extensively, but adjacent
clusters were separated by 'gorges' a few micrometers deep; lipid packing was
also less regular and tight in the intercluster region. Two quantitatively
different hydrophilic pathways were found in the horny layer: an intercluster
route with low penetration resistance comprising < or = 1% of the total or < or =
20% of the pathway area in the skin, and an intercorneocyte pathway that resists
penetration better and is more abundant (> or = 3% of the skin or > or = 80% of
the pathway area). This latter route is strongly tortuous, as it goes between all
the corneocytes in a cluster. It traces the irregularities between the
intercellular lipid lamellae and/or the adjacent corneocyte envelopes which may
act as virtual channels in the skin. It was inferred that such channels coincide
with the route of water evaporation through the skin and exhibit the permeability
barrier maximum in the stratum corneum conjunctum.
PMID- 9640362
TI - Application of confocal laser scanning microscopy to differential diagnosis of
bullous pemphigoid and epidermolysis bullosa acquisita.
AB - We applied confocal laser scanning microscopy to fluorescence overlay antigen
mapping (FOAM) for differential diagnosis of bullous pemphigoid (BP) and
epidermolysis bullosa acquisita (EBA). FOAM of tissue-bound IgG and marker
basement membrane components (BMCs) including integrin beta 4, laminin-1, laminin
5 and type IV collagen, showed that tissue-bound IgG in perilesional skin samples
from five patients with BP was localized on the epidermal side of type IV
collagen, and colocalized with some of the other three BMCs, whereas IgG in a
sample from a patient with EBA was on the dermal side of all the BMCs. FOAM of
binding sites of autoantibodies in patients' sera and markers including integrin
beta 4, laminin-1, type IV collagen and type VII collagen, showed that the
binding sites of autoantibodies from 16 patients with BP were localized on the
epidermal side of type IV and type VII collagens, and localized above or
codistributed with integrin beta 4 and laminin-1, whereas those from five
patients with EBA were codistributed with type IV and type VII collagens, and
localized on the dermal side of integrin beta 4 and laminin-1. These spatial
relationships are compatible with their previously described ultrastructural
locations. Thus, this method appears to be useful in the differential diagnosis
of BP and EBA.
PMID- 9640363
TI - Mucous membrane pemphigoid: a dual circulating antibody response with IgG and IgA
signifies a more severe and persistent disease.
AB - Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease frequently
associated with scarring of involved clinical sites. At present, therapeutic
intervention in the form of immunomodulating or immunosuppressive agents is often
reserved until the onset of significant inflammation and/or early cicatrization.
We have therefore studied the clinical and immunopathological findings in 67
patients with MMP in order to try to establish a reliable prognostic indicator by
which patients at high risk may be identified early in the disease. Inclusion
criteria were a predominantly mucosal disease and the detection of IgG and/or C3
anti-basement membrane zone (BMZ) immunoreactants using immunofluorescence
techniques. Patients were allocated to three disease subgroups on the basis of
the modality and duration of therapeutic intervention required to achieve
effective control of disease. In addition, at presentation and at each follow-up
visit, a clinical score for severity of involved clinical sites was awarded and
serum collected for indirect immunofluorescence (IIF). A dual circulating anti
basement membrane zone (anti-BMZ) antibody response with IgG and IgA was
significantly associated with a more severe and persistent disease profile (P <
0.001). The odds ratios for requiring systemic therapy were: 11.6 among patients
in whom there was a clinical score > or = 5 compared with a score < 5, and 31.3
and 66.9 among patients with IgG alone and both IgG and IgA, respectively,
compared with negative IIF. The findings suggest that an assessment based upon a
combination of site severity score and the presence of circulating IgG and IgA by
IIF using 1 mol/L salt-split human skin substrate may be considered a useful
prognostic indicator.
PMID- 9640364
TI - Cytokine pattern in blister fluid and serum of patients with bullous pemphigoid:
relationships with disease intensity.
AB - Few and contrasting data are available in the literature concerning the levels of
various cytokines in blister fluid (BF) and in the serum of patients affected
with bullous pemphigoid (BP). Using commercially available ELISA kits, this study
reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients
and compares them with those of 15 control subjects' sera. Generally, no
significant differences were observed in BP and control sera. In contrast,
interleukin (IL) 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor
alpha (TNF-alpha) and interferon-gamma (IFN-gamma) showed increased BF levels as
compared with BP sera. Two cytokines, IL-11 and IL-12 did not show significant
differences between BP BF and sera, while an opposite behaviour was observed for
transforming growth factor beta 1 (TGF-beta 1), whose serum levels were higher
than the concentrations in BF. Using the number of lesions of the patients as a
possible disease intensity marker, significant correlations were found with the
BF levels of IL-1 beta, IL-8, TNF-alpha and, most closely, IL-5. These data may
have pathogenetic relevance and suggest the possibility that these biological
modulators may be used as a quantitative marker of disease intensity.
PMID- 9640365
TI - Expression of CD26/dipeptidyl-peptidase IV in benign and malignant pigment-cell
lesions of the skin.
AB - The T-cell activation antigen CD26 or dipeptidyl-peptidase IV (DPP-IV) belongs to
a group of membrane-bound proteases that are variably expressed by melanoma cell
lines. In vitro studies have suggested that loss of CD26 is associated with
tumour progression. To correlate its expression with the histological stage of
tumour progression of malignant melanoma (MM), we studied the distribution of
CD26/DPP-IV in paraffin sections of a series of 110 benign and malignant pigment
cell lesions of the skin using a cocktail of anti-CD26 monoclonal antibodies and
the three-step ABC method. Only two of 44 benign lesions focally expressed CD26
in their junctional compartment. In MM, expression of CD26 was not related to any
of the known histological prognostic factors, but was associated with the stage
of tumour progression; thus, CD26 was expressed in the situ or invasive radial
growth phase in 34% of MM, whereas only 12% of MM expressed CD26 in the vertical
growth phase. No CD26 expression occurred in metastatic melanomas. These data
suggest that this proteinase plays a part in the early invasion of MM. Thus, CD26
may serve in the binding to, and enzymatic degradation, components of the
extracellular matrix of the papillary dermis. Loss of CD26 in the vertical growth
phase may contribute to the insufficient inactivation of regulatory peptides and
unlimited action of growth factors.
PMID- 9640366
TI - The intradermal effects of the H3 receptor agonist R alpha methylhistamine in
human skin.
AB - We have investigated the possible existence of the H3 histamine receptor in human
skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3
agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of
RAMHA with histamine, and studied their potential modulation by the H1 antagonist
terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide
on codeine phosphate-, substance P- and histamine-induced weal and flare
responses were also studied. RAMHA produced dose-related weal and flare responses
that were approximately 10- and fivefold less, respectively, than responses to
histamine. Flare responses to RAMHA were significantly inhibited by oral
terfenadine (P < 0.05). Weal and flare responses to histamine after oral
cimetidine showed much intersubject variation, and cimetidine did not
significantly alter either RAMHA- or histamine-induced weal and flare responses.
Codeine phosphate-, substance P- and histamine-induced responses were not
significantly affected by concurrent administration of RAMHA. Thioperamide was
not found to influence codeine phosphate-, substance P-, RAMHA- or histamine
induced effects. RAMHA induces vascular (weal and flare) responses in human skin,
and these responses are partially inhibited by terfenadine. There is a trend for
RAMHA to have an additive effect to the weal induced by substance P and
histamine, although our results largely do not reach statistical significance.
Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate,
histamine or substance P. We cannot conclude that the effects of RAMHA are
induced by H3 receptors on cutaneous endothelial or mast cells.
PMID- 9640367
TI - Celtic ancestry, HLA phenotype and increased risk of skin cancer.
AB - Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer
than non-Celts, and various positive and negative associations between certain
human leucocyte antigen (HLA) phenotypes and the development of skin cancer have
been described. The aims of this study were to determine whether any HLA
phenotypes are associated either with Celtic or non-Celtic ancestry, or skin
type. One thousand and ten members of the Welsh Bone Marrow Donor Registry
(WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire
which enquired as to their family origins and their 'Index of Celtic Ancestry'
scored out of 12. Three groups were identified: non-Celts (score < 3), Celts
(score > 9), and a subset of the Celts--'high scoring' Celts (score > 10).
Details of hair and eye colour and skin type were also requested. Skin type and
HLA-A, -B, -DR and -DQ frequencies were compared between the three groups (Celts,
non-Celts and 'high scoring' Celts), and a random indigenous population of 9196
members of the WBMDR. Seven hundred and thirty-six replies were received (279
male, 457 female, mean age 31 years). One hundred and forty-four Celts, 51 'high
scoring' Celts and 170 non-Celts were identified. Forty-six (32%) Celts had skin
type I or II compared with 36 (21%) non-Celts (P = 0.039), and 37 (73%) 'high
scoring' Celts had skin type I or II (P < 0.0001). However, there were no
significant differences between the groups with regard to hair colour, eye colour
or number of episodes of painful sunburn. The frequency of HLA-DR4 was 32% in the
non-Celtic group, 44% in the Celtic group (not significant), and 53% in the 'high
scoring' Celts (P = 0.008). However, the difference was not significant after
correction. There were no significant associations between skin type and HLA
phenotype. HLA-DR4 is known to be associated with an increased risk of both basal
cell carcinoma and malignant melanoma and its increased frequency in Celts may be
an independent risk factor for skin cancer in addition to skin type.
PMID- 9640368
TI - Effects of nitrazepam on nocturnal scratching in adults with atopic dermatitis: a
double-blind placebo-controlled crossover study.
AB - We investigated the effect of nitrazepam on nocturnal scratching in 10 adult out
patients with atopic dermatitis (AD) using a double-blind placebo-controlled
crossover method. Patients were given either nitrazepam (Benzalin tablets
containing 5 mg nitrazepam) or a placebo on 3 successive nights, with a washout
interval of 4 days. We used an infrared video camera to identify bouts of
scratching lasting more than 5 s. These were counted and the duration of all the
bouts of scratching (total scratching time, TST) was calculated. The percentage
of TST to total recording time (TST%) was used as an index of nocturnal
scratching. The frequency with which bouts of scratching (bouts/h) occurred was
reduced by 10 mg nitrazepam (7.7 +/- 3.6 with nitrazepam vs. 9.6 +/- 3.6 with
placebo, P < 0.05). However, the mean duration (s/bout) of the bouts of
scratching was longer with 10 mg nitrazepam (32.3 +/- 23.4 with nitrazepam vs.
19.1 +/- 10.0 with placebo, P < 0.05). As a result, there was no significant
difference between TST% (6.5 +/- 4.2 with nitrazepam vs. 5.4 +/- 3.8 with
placebo, not significant). All the above values are mean +/- SD. The degree of
itching and the condition of the AD did not change during the 2 weeks of the
study. We conclude that taking 10 mg nitrazepam is not an effective way of
reducing the total duration of nocturnal scratching in AD patients, although it
decreases the frequency with which bouts of nocturnal scratching occur.
PMID- 9640369
TI - The characteristics of urticaria in 390 patients.
AB - Data were collected on 390 patients who attended a dermatology out-patient
department in whom a clinical diagnosis of urticaria was made. Two hundred and
thirty-seven (61%) were women. The median age at onset of symptoms was 40 years.
Sixty-one (16%) had acute urticaria with symptoms of less than 6 weeks duration
at presentation. The disorder was deemed idiopathic in 217 (56%) patients, 59
(15%) had physical urticaria and 57 (15%) had both idiopathic and physical
urticaria. Thirty-eight (10%) patients reported intolerance to salicylate or
similar drugs, and 31 of these 38 patients also had idiopathic symptoms. One
hundred and seventy-two (44%) patients reported a good response to treatment with
H1 receptor antagonists. Those who gained little or no benefit from these drugs
were more likely to have a physical urticaria (P < 0.05) or to report intolerance
reactions (P < 0.05). Only 113 (29%) patients were asymptomatic when discharged.
One in five of a small sample contacted still had symptoms 10 years after
presentation. Patients seen in an urticaria clinic were less likely to have
routine investigations performed and more likely to be discharged at first
attendance. When compared with previous published surveys, these figures show a
lower proportion of intolerance reactions and a greater proportion of patients
responding well to treatment with antihistamines.
PMID- 9640370
TI - Successful treatment of facial blushing by endoscopic transthoracic
sympathicotomy.
AB - Facial blushing is one of the cardinal symptoms of social phobia and has a strong
negative impact on the quality of life. Traditional therapeutic options are
psychotherapy and pharmacological treatment. The results of these treatments on
facial blushing are poorly documented. To investigate whether endoscopic
bilateral transection of the upper thoracic sympathetic chain is efficient in the
treatment of facial blushing, 244 consecutive patients were treated with
bilateral endoscopic transthoracic sympathicotomy (ETS). The results were
evaluated by questionnaire and symptoms assessed with visual analogue scales (0
10). There was no mortality nor conversion to open surgery. No Horner's syndrome
occurred. Two patients with postoperative pneumothorax were treated with
intercostal drainage and one small pulmonary embolus was detected. The
questionnaire was answered by 219 patients (90%) a mean (+/- SEM) of 8 months (+/
9 days) after surgery. Facial blushing (mean +/- SEM) was reduced from 8.7 +/-
0.1 to 2.2 +/- 0.2, P < 0.0001, by the operation. Heart palpitations in stressful
situations were also reduced (3.7 +/- 0.3 to 1.3 +/- 0.1, P < 0.0001). The
quality of life was substantially improved. The main side-effect was
redistribution of sweating from the upper to the lower part of the body.
Increased sweating of the trunk occurred in 75% of the patients. Overall, 85% of
the patients were satisfied with the result and 15% were to some degree
dissatisfied, mainly due to insufficient effect, but only four patients (2%)
regretted the operation. As this is an open study, the results must be viewed
with caution. ETS, however, appears to be an efficient, safe and minimally
invasive surgical method for the treatment of facial blushing.
PMID- 9640371
TI - Leucoderma treated by transplantation of a basal cell layer enriched suspension.
AB - The aim of this study was to test the usefulness of a melanocyte-enriched cell
suspension for the treatment of leucoderma. After removal of a superficial (4-30
cm2) skin sample, the cells were mechanically separated in a trypsin-EDTA
solution, centrifuged and washed in a melanocyte medium. The melanocyte-enriched
epidermal cell suspension devoid of stratum corneum and stratum granulosum was
then applied to the dermabraded depigmented skin. The 26 patients treated had
piebaldism (three), vitiligo vulgaris (17), segmental vitiligo (three), halo
naevi (one), naevus depigmentosus (one) and chemical leucoderma (one). In
patients with widespread piebaldism we found that by diluting the cell suspension
the recipient area could be increased to up to 10 times the size of the donor
area with the same good results as without or with less dilution. In patients
with vitiligo areas of between 50 and 90 cm2, the recipient areas were increased
three- to fivefold in the donor area. Patients with piebaldism, segmental
vitiligo and halo naevi healed completely, as did most patients with vitiligo. In
naevus depigmentosus no effect was seen. Our new method for treatment of
leucoderma has the advantage that cell culture is not needed and that it is more
suitable than epidermal sheet grafts when several small areas are to be treated.
PMID- 9640372
TI - The detection of human papillomavirus DNA in skin tags.
AB - Human papillomavirus (HPV) is associated with benign cutaneous or mucosal lesions
and with malignant tumours, but none of the HPV types has so far been related to
skin tags. Skin biopsy specimens from 49 Caucasian patients suffering from the
presence of multiple soft fibromas were analysed by means of dot blot
hybridization and by polymerase chain reaction assays aimed at detecting all
known HPV types. The results revealed the presence of HPV DNA type 6/11 in 88% of
the skin tags examined. This result supports the hypothesis that HPV plays a part
in the progression of cutaneous soft fibromas, as previously reported for
laryngeal papillomas.
PMID- 9640373
TI - Nodular localized cutaneous amyloidosis: further demonstration of monoclonality
of infiltrating plasma cells in four additional Japanese patients.
AB - Nodular localized cutaneous amyloidosis (NLCA) is a disorder characterized by
deposition of amyloid derived from immunoglobulin light chains. We used semi
nested polymerase chain reaction (PCR) to analyse archival paraffin-embedded
sections from a previous patient and from four additional, previously reported
patients with NLCA to determine whether involvement of monoclonal plasma cells is
a universal feature of this condition. The semi-nested PCR analysis revealed one
or two amplified bands, around 100-120 bp, for all five cases of NLCA, although
the yields varied from case to case. These results suggest that clonal expansion
of plasma cells in NLCA may occur locally.
PMID- 9640374
TI - X-linked ichthyosis: relation between cholesterol sulphate,
dehydroepiandrosterone sulphate and patient's age.
AB - Steroid sulphatase deficiency is a feature of recessive X-linked ichthyosis
(RXLI) that causes the accumulation of sulphated steroids (SS) in various organs
and cells. In a previous study, we detected elevated cholesterol sulphate (CS)
and dehydroepiandrosterone sulphate (DHEAS) serum levels in a group of 15 RXLI
patients selected in a narrow age range. In the present study both CS and DHEAS
serum levels were qualitatively and quantitatively determined using gas
chromatographic analysis in a group of 33 RXLI patients ranging in age from 3 to
70 years. The levels of CS and DHEAS were significantly increased in all
patients. Variations in SS were related both to patients' ages and clinical
course of the disease; Serum SS levels start to increase in early infancy, peak
at puberty, remain elevated in adults and decrease slightly in the elderly.
PMID- 9640375
TI - Prevalence of undetected tinea capitis in a prospective school survey in Madrid:
emergence of new causative fungi.
AB - From October 1994 to December 1996, a prospective study was undertaken in 10,000
unselected school children in Madrid, aged between 2 and 16 years (mean +/- SD
8.5 +/- 3.6 years). Fifty-two (0.52%) (including 13 immigrants from Africa) had
dermatophytes in the scalp: 33 (0.33%) (including 10 immigrants from Africa) had
tinea capitis and 19 were scalp carriers. Almost half of the symptomatic cases
were caused by Trichophyton tonsurans (12 of 33 cases) and Microsporum canis (16
of 33 cases). T. tonsurans (13 of 19 cases) was the predominant species in the
scalp carriers. Twenty-four per cent of the subjects with tinea capitis and 42%
of the asymptomatic scalp carriers also had ringworm in other body sites. There
was a significantly higher occurrence of tinea capitis (P < 0.001) (particularly
due to T. tonsurans: P < 0.001) and of asymptomatic scalp carriers (P < 0.05)
(particularly due to anthropophilic species: P < 0.01) in the immigrant
population from Africa.
PMID- 9640376
TI - Prognostic implications of determining 180 kDa bullous pemphigoid antigen (BPAG2)
gene/protein pathology in neonatal junctional epidermolysis bullosa.
AB - Epidermolysis bullosa (EB) in neonates is often difficult to characterize, both
in terms of making a precise diagnosis and in being able to comment accurately on
the prognosis for the affected child. We present a case of a neonate with
inherited mucocutaneous fragility and failure to thrive and detail our laboratory
approach for classifying the subtype of EB in this child. Mutational analysis
revealed a homozygous non-sense mutation in the gene encoding the 180 kDa bullous
pemphigoid antigen, also known as type XVII collagen, predicting a non-lethal
form of junctional EB. Identification of the underlying molecular pathology in
this case was of use in improving diagnosis, classification, management and
counselling.
PMID- 9640377
TI - Localized mucosal involvement and severe pulmonary involvement in a young patient
with paraneoplastic pemphigus associated with Castleman's tumour.
AB - We describe a 19-year-old female patient who developed recurrent ulcerations
limited to the orogenital mucosa for the last 3 years. She also developed
dyspnoea 5 months after the onset of the orogenital lesions. Castleman's tumour
of the retroperitoneum was found incidentally during routine physical
examination. The diagnosis of paraneoplastic pemphigus (PNP) was made by
pathological and immunological studies. The orogenital ulceration responded well
to corticosteroid therapy, but severe bronchiolitis obliterans progressed despite
intensive care. The patient eventually died from respiratory failure. This case
demonstrates the diversity of clinical features of paraneoplastic pemphigus.
PMID- 9640378
TI - Decreased activity of acid alpha-glucosidase in a patient with persistent
periocular swelling after infusions of hydroxyethyl starch.
AB - After infusion therapy with hydroxyethyl starch (HES) on account of sudden
hearing loss, a 68-year-old woman developed a marked and persistent periocular
swelling. This extraordinary adverse effect caused us to search for an
explanation by means of histopathology, immunohistochemistry, immunoelectron
microscopy and biochemistry. In lesional periocular skin and in normal-appearing
skin, lysosomal storage of HES could be detected with a specific HES antibody in
histiocytes, endothelial cells, basal keratinocytes and small nerves. In the
periocular skin, a stronger deposition of HES was found in addition to distinct
xanthomatous changes as well as features of lymphoedema. In view of lysosomal HES
storage we measured the pH-dependent activity of the lysosomal alpha-glucosidase
(GAA) in cultured fibroblasts. We found a 50% decreased activity of the acid GAA,
which is consistent with a heterozygous state of glycogenosis type II (Pompe's
disease) and potentially of pathogenetic relevance for the intralysosomal
accumulation of HES. Xanthomatous changes and lymphoedema are likely to be
secondary effects, but contribute considerably to the clinical manifestation of
persistent visible swelling. This observation could point to a role for GAA in
the elimination of tissue-stored HES. Patients with decreased activities of GAA
may be at risk of unusual adverse effects following extraordinary and prolonged
tissue storage of HES, especially if it is infused in large quantities.
PMID- 9640379
TI - Clear cell papulosis of the skin.
AB - Clear cell papulosis is a new entity first described in 1987. To date, six
patients have been reported: all were young Taiwanese children. The disease is
characterized clinically by multiple small, whitish maculopapules distributed
along the milk line and by the presence of large, benign pagetoid cells in the
epidermis resembling the clear cell of the nipple. The significance of this
entity lies in its potential histogenetic link with Paget's disease of the skin.
We report four new Taiwanese patients, three girls and one boy, aged between 21
months and 4 years. Two were sisters. Small hypopigmented macules first appeared
on the pubis. They were eventually distributed bilaterally along the milk line
but were most numerous in the public area. The disease may easily be overlooked
when the macules are tiny or few in number and thus display no clear milk-line
distribution, or when they occur in white-skinned individuals. Histologically,
solitary large clear cells with large, round pale nuclei were detected in the
basal layer of the hypomelaninized epidermis. The numbers of clear cells varied
on haematoxylin and eosin staining and were only small in two patients. The
cytoplasm of the clear cells was decorated by antikeratin AE1 and
anticarcinoembryonic antigen antibodies. AE1 was the best marker of the clear
cell. Some of the AE1-positive cells were tadpole-like in shape and were situated
well above the basal layer. Ultrastructurally, large clumps of disintegrated or
vacuolated mucin granules were present in the cytoplasm of the clear cells. The
melanocytes appeared normal; the suprabasal keratinocytes were essentially devoid
of melanosomes. The pathological findings in the present study support the
hypothesis that these clear cells are an aberrant derivative of sweat gland cells
in the epidermis and are potentially the precursor cells giving rise to mammary
and extramammary Paget's disease. The differential diagnosis includes chicken pox
scars, idiopathic guttate hypomelanosis, hypomelanotic tinea versicolor,
anetoderma and early, hypopigmented lesions of Paget's disease.
PMID- 9640380
TI - Porokeratotic eccrine ostial and dermal duct naevus with dermatomal trunk
involvement: literature review and report on the efficacy of laser treatment.
AB - Porokeratotic eccrine ostial and dermal duct naevus (PEODDN) is a rare, benign
hamartomatous malformation involving the eccrine sweat duct. The existence of
filiform keratinous plugs that represent cornoid lamellae overlying dilated
infundibula of eccrine ducts is a distinctive feature and the presence of
associated abnormal dermal ducts is frequent. We report a patient with PEODDN who
exhibited lesions on the left side of her chest. Cases of PEODDN reported in the
literature are reviewed. Our experience in treating this patient with ultrapulsed
carbon dioxide laser is also presented.
PMID- 9640381
TI - Paget's disease of the scrotum: a case exhibiting positive prostate-specific
antigen staining and associated prostatic adenocarcinoma.
AB - A 75-year-old man with carcinoma of the prostate presented with a pruritic,
erythematous plaque involving the scrotal skin. Histological examination revealed
extramammary Paget's disease. The intraepidermal tumour cells expressed prostate
specific antigen in keeping with a prostatic origin.
PMID- 9640382
TI - Angiosarcoma arising in a chronically lymphoedematous leg.
AB - Cutaneous angiosarcoma is a rare aggressive tumour of capillary and lymphatic
endothelial cell origin. It presents as multiple purple and red papules and
nodules on the head and neck or the extremities. We report an 86-year-old woman
with angiosarcoma arising on her chronically lymphoedematous right leg. The
lymphoedema, secondary to chronic immobility, had developed gradually over 40
years. No other family members had lymphoedema. The patient presented with a
plaque of friable tumour tissue on the lower right leg and dorsum of the foot,
and satellite lesions on the knee and groin which initially appeared to be
petechial haemorrhages. The satellite lesions in the groin grew into tumour
nodules. There was no evidence of a preceding malignancy, nor any operative
intervention to the affected limb or abdomen. Histological examination of all
tumour specimens revealed moderately to poorly differentiated angiosarcoma. She
died within 5 months of the first appearance of the skin nodules.
PMID- 9640383
TI - Spindle and pseudoglandular squamous cell carcinoma arising in lichen sclerosus
of the vulva.
AB - An 83-year-old woman presented with a vulval mass. Radical vulvectomy was
performed and histology showed a unique mixed picture of spindle, pseudoglandular
and classical squamous cell carcinoma arising in vulval lichen sclerosus.
PMID- 9640384
TI - Tripe palms associated with systemic mastocytosis: the role of transforming
growth factor-alpha and efficacy of interferon-alfa.
AB - Tripe palms are thickened, moss-like or velvety textured exaggerations of the
normal dermatoglyphics. The disease belongs to the spectrum of papulosquamous
paraneoplastic syndromes. Although suspected, the role of transforming growth
factor-alpha (TGF-alpha) has not been clearly established. A 54-year-old man with
systemic mastocytosis presented with thickening and darkening of the palms and
soles. We performed skin biopsies for light microscopy (including toluidine
blue), in situ hybridization and double labelling, and determination of serum
tryptase, histamine and TGF-alpha levels. Toluidine blue stained the mast cells
that had massively infiltrated the dermis. Tripe palm samples showed extensive
hyperkeratosis. The TGF-alpha probe reacted strongly with the mast cells that
also reacted with the antitryptase monoclonal antibody. Elevated tryptase,
histamine and TGF-alpha levels prior to interferon-alfa administration decreased
under treatment. The demonstration of TGF-alpha in infiltrating mast cells, the
clinical regression of tripe palms and the lowering of the serum level and the
mast cell molecular signal of the cytokine when systemic mastocytosis was
controlled by interferon-alfa, suggest a key role for TGF-alpha in this cutaneous
paraneoplastic syndrome.
PMID- 9640385
TI - Nodular secondary syphilis.
AB - Nodular secondary syphilis in a 23-year-old Indian man was characterized by
numerous papular, nodular and plaque skin lesions, without involvement of the
mucous membranes. The histopathology showed sarcoid-like granulomata with
lymphocytes, histiocytes, eosinophils, plasma cells and multinucleated giant
cells. The differential diagnosis included deep mycoses, leprosy, tuberculosis,
sarcoidosis and lymphoma. The results of serological tests and the rapid response
to penicillin indicated a correct diagnosis.
PMID- 9640386
TI - DNA image cytometry in sebaceous tumours of the Muir-Torre syndrome.
PMID- 9640387
TI - Terbinafine-induced lupus erythematosus.
PMID- 9640388
TI - Terbinafine-induced acute generalized exanthematous pustulosis.
PMID- 9640389
TI - Lamotrigine and phenobarbitone-associated hypersensitivity syndrome: resolution
without corticosteroids.
PMID- 9640390
TI - Flutamide-induced pseudoporphyria.
PMID- 9640391
TI - Giant oral aphthous ulcers induced by nicorandil.
PMID- 9640392
TI - Genital ulcers in a psoriasis patient using topical tazarotene.
PMID- 9640393
TI - Hyperkeratotic varicella zoster virus infection in an HIV-infected patient.
Successful treatment of persistent lesions with cryosurgery.
PMID- 9640394
TI - Resolution of severe molluscum contagiosum on effective antiretroviral therapy.
PMID- 9640395
TI - Nodular erythema elevatum diutinum in an HIV-1 infected woman: response to
dapsone and antiretroviral therapy.
PMID- 9640396
TI - Severe therapy-resistant necrotizing vasculitis associated with hepatitis C virus
infection: successful treatment of the vasculitis with extracorporeal
immunoadsorption.
PMID- 9640397
TI - PUVA for diffuse cutaneous reticulohistiocytosis.
PMID- 9640398
TI - Severe skin pain after combined ultraviolet B and ultraviolet A phototherapy for
atopic dermatitis.
PMID- 9640399
TI - Systemic plasmacytosis with deposition of interleukin (IL)-6 and elevated
expression of IL-6 mRNA in the skin lesions.
PMID- 9640400
TI - Irritant and allergic reactions are additive, not synergistic.
PMID- 9640401
TI - Imaging of incidentally discovered adrenal masses.
PMID- 9640402
TI - Selective oestrogen receptor modulators: potential therapeutic applications.
PMID- 9640403
TI - The aetiology of Graves' disease: what is the genetic contribution?
PMID- 9640404
TI - A population-based study of Graves' disease in Danish twins.
AB - OBJECTIVE: The aetiology of Graves' disease (GD) is generally thought to fit a
multi-factorial pattern of inheritance in which clinical disease develops on the
basis of genetic susceptibility interacting with environmental and endogenous
factors. In previous twin studies the probandwise concordance rates for
hyperthyroidism were as high as 0.86 in monozygotic twins and 0.20 in dizygotic
twins, indicating a very strong genetic influence. In these studies, however, no
effort was made to distinguish between GD and non-autoimmune hyperthyroidism, and
one study also included patients with simple non-toxic goitre, hampering if not
invalidating any conclusions. The aim of the present study was to determine
whether there is a genetic contribution in the aetiology of GD. DESIGN:
Historical cohort study of pairs of same-sex twins, with information on GD being
gathered by questionnaire surveys in the 1950s and 1960s. All available hospital
material was sought to verify the diagnosis, which was assigned on the basis of
clinical and histopathological evidence. The healthy co-twins were followed
through middle age by questionnaire surveys in the 1970s and 1980s. PATIENTS:
Same-sex twin individuals born between 1870-1920, included in a population-based
nationwide register. A total of 118 subjects indicated hospitalization due to GD.
A hospital record was available in 76 subjects. Of these, 55 (46 females and 9
males) could be classified as having GD. MEASUREMENTS: Pairwise and probandwise
concordance rates for GD in monozygotic and dizygotic twin pairs. RESULTS: The
probandwise concordance rates were 0.36 for monozygotic pairs and 0 for dizygotic
pairs. The pairwise concordance rates were 0.22 and 0 for monozygotic and
dizygotic pairs, respectively. The concordance rates were significantly (P =
0.012) higher in monozygotic than in dizygotic pairs. CONCLUSIONS: These results
confirm that genetic factors play an important role in the aetiology of Graves'
disease. However, they may not be as powerful as previously thought.
PMID- 9640405
TI - Serum leptin and insulin in paediatric end-stage liver disease and following
successful orthotopic liver transplantation.
AB - OBJECTIVE: Leptin, the product of the ob gene, is a postulated feedback regulator
of adiposity with appetite suppressant and catabolic effects. Catabolic states
are associated with decreased body fat mass as a result of both nutritional and
metabolic perturbation. Low serum leptin has been described previously in a
number of catabolic states. It has been unclear whether the observed changes in
leptin are a cause or consequence of changes in adiposity. Paediatric end-stage
liver disease (ESLD) is characterized by decreased body fat mass and poor linear
growth. Successful treatment by orthotopic liver transplantation (OLT) is
accompanied by increase in fat mass. We investigated the hypothesis that serum
leptin would be low in paediatric ESLD and that increase in body fat mass post
OLT would result in increased serum leptin. DESIGN: Serum leptin and insulin were
measured by radioimmunoassay in children with ESLD before and after successful
OLT and in age-matched controls. PATIENTS: Twenty-four children with ESLD
attending the outpatient department of King's College Hospital, London and 10 age
matched controls. MEASUREMENTS: Anthropometric measurements were performed
according to standard techniques and standard deviation (SDS) derived from
population standards. Serum leptin and insulin were measured by radioimmunoassay.
RESULTS: Serum leptin pre-OLT, leptin (4.06 micrograms/l, [3.45, 5.68] median,
with 25th and 75th interquartile ranges) was significantly lower than controls
(6.62 micrograms/l, [4.33, 8.05], P = 0.02). Following OLT, serum leptin fell to
levels which were significantly lower than pre-OLT values (3.32 micrograms/l,
[2.30, 3.99], P = 0.01). There was no significant difference between boys and
girls either pre-OLT (boys; 3.64 micrograms/l, [2.45, 5.57], girls; 4.14
micrograms/l, [3.18, 5.65]) or post-OLT (boys; 3.32 micrograms/l, [2.93, 3.62],
girls; 3.69 micrograms/l, [2.23, 4.63]. Neither the age at OLT nor the age at the
time of blood sampling was correlated with serum leptin pre-OLT or post-OLT. Pre
OLT the children were significantly malnourished with low measures of body fat
mass (mid-arm circumference (MAC) SDS -1.90 [-4.67, -1.07]; triceps skinfold
thickness (TSF) SDS -1.53, [-2.23, -0.23]; body mass index (BMI) 16.2, [15.5,
16.9]). Three months post-OLT, there were significant improvements in MAC SDS (
0.77, [-1.08, -0.20], P = 0.02) and TSF SDS (-0.41, [-1.95, -0.38], P = 0.003),
but no significant change in BMI (15.9 [15.3, 16.7], P = 0.41. Pre-OLT, log serum
leptin did not correlate with BMI, MAC SDS or TSF SDS. In contrast, post-OLT,
there was a positive correlation between log serum leptin and BMI (r = 0.59, P =
0.003), MAC SDS (r = 0.49, P = 0.01) and TSF SDS (r = 0.41, P = 0.05). BMI also
correlated with log serum leptin in the control children (r = 0.64, P = 0.04).
CONCLUSIONS: Serum leptin is low in children with end-stage liver disease but
does not show the expected correlation with measures of body fat mass.
Surprisingly, following orthotopic liver transplantation serum leptin falls
significantly despite significant increases in measures of body fat mass (triceps
skinfold thickness standard deviation scores, mid-arm circumference standard
deviation scores). Orthotopic liver transplantation restores the expected
correlation of serum leptin with measures of body fat mass within the treatment
group. The elevation of serum leptin above predicted levels in paediatric end
stage liver disease offers a mechanism for the anorexia and cachexia
characteristic of this disease.
PMID- 9640406
TI - Effect of isoprenaline on plasma leptin and lipolysis in humans.
AB - OBJECTIVE: The sympathetic nervous system may play a central role in the
regulation of both lipolysis and leptin production. Therefore, we investigated
the effect of intravenous infusions of the beta-adrenergic agonist isoprenaline
on plasma concentrations of leptin and nonesterified fatty acids. DESIGN AND
PATIENTS: Eight lean, healthy human volunteers, (4M:4F; median (interquartile
range) age 36.5 (30.8-40.0) years; BMI 22.9 (20.1-29.2) kg.m-2; % body fat 24.5
(17.9-26.3)), were studied following an overnight fast. Intravenous infusion of
isoprenaline was carried out for 3 h, followed by a 1 hour recovery phase. The
isoprenaline infusion rates (0.5-3.5 micrograms.min-1) were titrated individually
for each subject in order to achieve similar biological sympathetic responses
based on heart rate (target heart rates were > 100 min-1 but < twice resting
heart rate). MEASUREMENTS: Plasma leptin was determined using an in-house
radioimmunoassay, nonesterified fatty acids estimated with an enzymatic
colourimetric assay and insulin concentrations were assayed using a specific, two
site immunoenzymometric assay. RESULTS: Fasting preinfusion plasma leptin
concentrations (6.3 (3.0-12.8) micrograms/l) correlated with percentage body fat
measured by bioimpedance (r = 0.95; P < 0.001). Plasma leptin concentrations were
rapidly suppressed by isoprenaline, with maximal suppression (20.5 (15.0-25.0)%
of preinfusion levels (Wilcoxon rank sum test; P < 0.05)), observed after 2 h. In
the recovery period, plasma leptin concentrations rapidly returned to preinfusion
levels (postinfusion vs maximally suppressed leptin concentrations P < 0.05; vs
preinfusion leptin concentrations P = NS). Plasma nonesterified fatty acids and
insulin concentrations showed opposite changes to those observed with leptin.
CONCLUSION: Plasma leptin concentrations are rapidly and reversibly suppressed by
the infusion of isoprenaline in humans in vivo.
PMID- 9640407
TI - Serum follistatin concentrations are increased in patients with septicaemia.
AB - OBJECTIVE: Follistatin (FS) is the specific binding protein of activin, a growth
and differentiation factor of many cell types. Both factors have almost
ubiquitous tissue distributions. In vitro, FS is secreted by vascular endothelial
cells and this can be stimulated by bacterial compounds. For this reason, serum
FS levels were examined in patients with septicaemia. PATIENTS: Five male and
four female patients of different age with various forms of septicaemia and
different clinical outcome. MEASUREMENTS: Serum concentrations of FS, C-reactive
protein (CRP) and blood leucocyte counts were determined repeatedly in all nine
patients; samples from age- and sex-matched healthy volunteers served as
controls. RESULTS: The median of the maximum FS concentrations of septicaemic
patients was threefold higher than in healthy controls (P = 0.008). The highest
increase observed was approximately 40 times normal. Serum FS levels in patients
with septicaemia showed large variations between individuals. Serum FS levels
parallelled those of CRP but were not correlated to the leucocyte counts.
CONCLUSION: Serum follistatin concentrations in humans are elevated during
septicaemia and appear to parallel serum C-reactive protein levels.
PMID- 9640408
TI - An audit of the management of thyroid cancer in a district general hospital.
AB - OBJECTIVE: Thyroid cancer is the commonest endocrine malignancy yet it appeared
to present infrequently to the endocrinologists at this large District General
Hospital. The management of well-differentiated thyroid cancer remains
controversial with a wide variation in clinical practice. The aim of this survey
was to determine the characteristics of the patients diagnosed with thyroid
cancer and whether any deficiencies existed in the management of subjects
diagnosed with thyroid cancer over a five-year period using standards of care
based upon long-term outcome data and recently published USA guidelines. DESIGN
AND PATIENTS: Retrospective case-note survey of all patients newly registered
with thyroid cancer from 1990 to 1994 in North Staffordshire (estimated total
population 450,000). RESULTS: The annual incidence of all thyroid cancer was two
per 100,000 of which well-differentiated tumours comprised 70%. Medical records
were obtained in 48 new cases (91% of total) identified. Fifteen subjects who
presented as surgical emergencies received only palliative treatment and had a
poor outcome. Two patients presented with metastatic medullary thyroid carcinoma
(3% of total). Thirty-one patients (97% of whom presented with a thyroid nodule)
were referred electively to either surgical (n = 22), ENT (n = 2) or
endocrinology (n = 7) outpatients with well-differentiated papillary (n = 17) and
follicular (n = 14) tumours. Thirteen patients (42%) had fine-needle aspiration
cytology performed preoperatively. Of the 22 tumours (71%) greater than 1.5 cm,
five (27%) had a total thyroidectomy and two (9%) also had radioiodine ablation.
There was inadequate serum thyrotrophin suppression postoperatively in 12
patients (39%) and only five (16%) were being monitored for recurrence with serum
thyroglobulin measurements. CONCLUSIONS: Deficiencies in the optimum management
of small, well-differentiated thyroid cancers were identified. Improved
communication between specialties has led to the development of an agreed
management protocol to increase the quality of care offered to patients with
thyroid cancer and for auditing the coordinated service in the future.
PMID- 9640409
TI - Retinoid X receptor expression in the normal pituitary and clinically 'non
functioning' pituitary tumours.
AB - OBJECTIVE: The glycoprotein hormone common alpha-subunit is frequently expressed
in clinically 'non-functioning' tumours (NFTs) of the anterior pituitary, despite
normal levels of T3 and gonadal steroids. This observation suggests abnormal
negative-feedback regulation of the alpha-subunit by T3 and gonadal steroids in
NFTs. We have previously documented reduced expression of thyroid hormone
receptor (TR) variants in NFTs compared to normals and proposed that this
observation may, in part, explain the defective negative regulation. Due to the
important role of retinoid X receptors (RXRs) in transactivating TR-mediated
transcriptional regulation, via heterodimer formation, we hypothesize that
aberrant RXR isoform expression in NFTs may contribute to the defective negative
regulation of the alpha-subunit by T3. DESIGN: Comparison of RXR isoform protein
and mRNA expression in NFTs and normal pituitaries. PATIENTS AND TUMOURS: Twenty
clinically non-functioning pituitary tumours and 27 normal pituitaries were
obtained for analysis. MEASUREMENTS: Immunocytochemistry and semiquantitative RT
PCR was performed on tumours and normal pituitaries to determine the relative
levels of expression of RXR isoform proteins and mRNAs, respectively. RESULTS:
RXR alpha was expressed in a similar proportion (approximately 50%) of both
normal human pituitaries and NFTs, while RXR beta and gamma were each observed in
26% of normals but were undetectable in NFTs. The application of semiquantitative
RT-PCR revealed similar levels of mRNAs encoding the RXR alpha and RXR beta
isoforms in normals and NFTs but significantly reduced expression of RXR gamma
mRNA was observed in NFTs. CONCLUSIONS: We propose that abnormal RXR isoform
expression in clinically 'non-functioning' pituitary tumours may contribute to
abnormal T3-mediated negative regulation of alpha-subunit production.
PMID- 9640410
TI - Clinical profile of primary hyperparathyroidism in adolescents and young adults.
AB - OBJECTIVE: Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed
condition among adolescents and young adults. We review the clinical
characteristics of these patients based on our institutional experience.
SUBJECTS: Patients aged 12-28 years treated for PHPT at our institution from 1990
to 1996 were evaluated by a review of medical records and current follow-up data.
This consisted of 22 patients (8M:14F), constituting approximately 3% of all
patients operated for PHPT during this period. MEASUREMENTS: Serum and urinary
calcium concentrations, renal function, and serum intact parathyroid hormone
(IPTH) levels were measured in all patients. After biochemical confirmation of
diagnosis, the patients completed a questionnaire to evaluate the presence of
symptoms and/or conditions associated with PHPT. All the patients underwent
parathyroidectomy and their tumour characteristics were evaluated. Surgical
outcome was determined by measurements of serum calcium and IPTH levels
postoperatively and during long-term follow-up. RESULTS: A third of the patients
were diagnosed by routine serum chemistry whereas two-thirds presented with
symptoms or conditions associated with hypercalcaemia. Non-specific complaints
such as fatigue or exhaustion, and weakness or lethargy constitute the most
common findings on questionnaire review. A family history of PHPT was present in
only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to
4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical
pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas
and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young
adults (aged 19-28 years) revealed no differences in the clinical, pathological
or laboratory profiles, except for a male predominance in adolescent patients.
Fifteen patients had resection of one or more adenomas while 7 underwent subtotal
parathyroidectomy. Six patients (27%) were reoperated cases, all received primary
treatment elsewhere. All patients with benign PHPT were cured surgically, with a
median follow-up of 47 months (range 3-77 months). One reoperated patient
developed permanent hypocalcaemia. One patient with carcinoma underwent several
operations for recurrence; he is now eucalcaemic despite persistent disease at 80
months from diagnosis. CONCLUSIONS: We found a high incidence of multiglandular
disease and relatively non-specific symptomatology in our adolescent and young
adult patients with primary hyperparathyroidism. In view of the heterogeneous
clinical expression noted in young patients, one should consider primary
hyperparathyroidism in the differential diagnosis of unexplained non-specific
complaints, and perform serum calcium estimations more readily in these subjects.
Our experience suggests that primary hyperparathyroidism can be a serious disease
with significant morbidity if left untreated, whereas parathyroidectomy provides
successful results.
PMID- 9640411
TI - TSH receptor antibody-associated thyroid dysfunction following subacute
thyroiditis.
AB - OBJECTIVE: Autoimmunity plays an important role in the development of
thyrotrophin (TSH) receptor antibodies and the pathogenesis of Graves' disease
and Hashimoto's thyroiditis. On the other hand, subacute thyroiditis is a self
limited inflammatory disease of presumed viral aetiology. The aim of this study
was to examine whether subacute thyroiditis triggers TSH receptor antibody
associated thyroid disorders. PATIENTS: We reviewed 1,697 patients with subacute
thyroiditis seen between 1985 and 1995. DESIGN AND MEASUREMENTS: We measured
antibodies which inhibit the TSH binding to the TSH receptor (TBIAb), thyroid
stimulating antibodies (TSAb) and antibodies that block TSH action (TBAb). Other
thyroid autoantibodies were also determined. RESULTS: TBIAb became positive in 38
patients following subacute thyroiditis. Thyroid function after the development
of TBIAb appeared to be influenced by the bioactivity of the antibody.
Hyperthyroidism developed in the presence of TSAb, and so did hypothyroidism in
the presence of TBAb, although 21 patients did not have thyroid dysfunction
despite high titres of TBIAb. Fifteen out of 17 patients recovered from
hyperthyroidism or hypothyroidism after the disappearance of TBIAb sometimes even
without medication. TBIAb-positive patients had a high incidence of a family
history of thyroid disease and positive anti-thyroid microsomal antibodies. An
ophthalmopathy similar to Graves' disease was also observed in 3 patients.
CONCLUSIONS: Subacute thyroiditis may trigger autoreactive B cells to produce TSH
receptor antibodies, resulting in TSH receptor antibody-associated thyroid
dysfunction in some patients.
PMID- 9640412
TI - Serum collagen crosslinks as markers of bone turn-over during GH replacement
therapy in growth hormone deficient adults.
AB - OBJECTIVES: Bone metabolism is an important target for GH replacement therapy.
However, in adults, treatment periods exceeding 12 months are required for a
positive effect of GH on bone mineral density. Thus, to detect an early effect of
GH on bone, markers of bone turn-over are important. Pyridinoline (PYR) and
deoxypyridinoline (DPYR) are well-defined sensitive markers of bone resorption,
but to date only urinary assays have been available. We report the use of a novel
assay to measure changes in serum PYR and DPYR in GH deficient (GHD) adults
during GH replacement therapy. STUDY DESIGN: The study consisted of a 6-month
randomized, double-blind, placebo-controlled study of the administration of GH
(Genotropin) (0.25 IU/Kg/week (0.125 IU/kg/week for the first four weeks))
followed by a 6-month open phase of GH therapy. PATIENTS: Thirty-five GHD adults
(17 women; mean age 39.8 years; range 21.1-59.9) on conventional hormone
replacement therapy as required, were studied. MEASUREMENTS: Bone formation was
analysed using serum bone alkaline phosphatase (BAP) and serum osteocalcin (OC).
Bone resorption was analysed using serum pyridinoline (PYR) and serum
deoxypyridinoline (DPYR). Bone mineral density (BMD) was determined by dual
energy X-ray absorptiometry (DEXA). RESULTS: After 6 months placebo treatment
there were no significant changes in any of the bone markers analysed, nor in
BMD. In the active arm of the study there was a significant increase in serum OC,
BAP, PYR and DPYR (P = 0.03, P = 0.004, P = 0.003 and P = 0.01, respectively),
remaining significantly elevated over their baseline levels for the subsequent 6
months of treatment (P = 0.04, P = 0.009, P = 0.003 and P = 0.04, respectively).
No changes were observed in BMD in any of the groups after 6 months GH treatment.
In the active arm of the study, after 12 months GH treatment there was a
significant increase in BMD at both the lumbar spine and femoral neck (P = 0.01
for both sites). CONCLUSIONS: In summary, the present study confirms that
administration of GH treatment to GHD adult patients significantly activates bone
remodelling, with the effect of GH both in bone formation and bone resorption
markers being maximal after 6 months of treatment. The serum assay for PYR and
DPYR has a number of practical and theoretical advantages over the urine assay
and gave similar results to those previously reported for the urine assay.
PMID- 9640413
TI - Long-term change in the bone mineral density of adults with adult onset growth
hormone (GH) deficiency in response to short or long-term GH replacement therapy.
AB - OBJECTIVE: Only two previous studies have assessed the effects of long-term GH
replacement therapy on bone mineral density (BMD) in patients with adult onset GH
deficiency. To date no study has looked at the long-term impact on BMD after a
short course (6-12 months) of GH replacement. In two groups of patients with
adult onset GH deficiency we have studied BMD either (a) after 3 years of
continuous GH replacement or (b) 2 years after completion of a short course of
GH. DESIGN: An open GH therapeutic study in which patients were recruited from a
previous double-blind placebo-controlled study. The BMD status of all patients
was unknown to the physician and patient at the time of recruitment. PATIENTS:
Group A (n = 7, three females) all received GH replacement continuously for 3
years. Group B (n = 8, five females) included six patients who received GH
replacement for 6 months and two who received GH replacement for 12 months with
BMD being measured at 6-monthly intervals. METHODS: Single photon absorptiometry
(SPA) and later single X-ray absorptiometry (SXA) were used to measure forearm
cortical BMD. Dual-energy X-ray absorptiometry (DXA) was used to measure lumbar
spine, trochanteric, femoral neck and Ward's area BMD. RESULTS: In group A lumbar
spine and trochanter BMD had increased significantly from baseline by 3.7% (DXA:
median change = 0.045 g/cm2; P = 0.028) and 4.0% (DXA: median change = 0.031
g/cm2; P = 0.046), respectively. There were non-significant decreases in femoral
neck (1.9%) (DXA: median change = -0.02 g/cm2; P = 0.39), Ward's area (6.5%)
(DXA: median change = -0.06 g/cm2; P = 0.09) and forearm (2.6%) (SPA/SXA: median
change = -0.013 g/cm2; P = 0.18). In group B, compared with baseline, only
trochanter BMD changed significantly, increasing by 5.9% (DXA: median change =
0.0485 g/cm2; P = 0.049). Lumbar spine (DXA: median change = -0.001 g/cm2) Ward's
area (DXA: median change = 0.0135 g/cm2), femoral neck (DXA: median change =
0.005 g/cm2) and forearm cortical (SPA/SXA; median change = -0.01 g/cm2) BMD did
not change significantly (P = 0.67, P = 0.57, P = 0.86 and P = 0.31,
respectively). Median percentage changes compared with baseline were -0.1%, 1.8%,
-0.5% and -2.1%, respectively. From the time of completion of GH therapy however,
BMD increased significantly at lumbar spine, (median change = 0.023 g/cm2),
Ward's area (median change = 0.03 g/cm2) and trochanter (median change = 0.056
g/cm2) (P = 0.036, P = 0.049 and P = 0.012, respectively) but not at the femoral
neck (median change = 0.017 g/cm2; P = 0.31) or forearm (median change = 0 g/cm2;
P = 0.75). CONCLUSION: Long-term GH replacement therapy for three years appears
to have beneficial effects on bone in patients with adult onset GH deficiency
particularly at the lumbar spine and trochanter; the effects on femoral neck and
forearm cortical BMD, however, are less impressive. A short course (6-12 months)
of GH replacement therapy results in an increase in trochanter BMD several years
later, and after an initial decline in BMD whilst on GH replacement, lumbar spine
and Ward's area BMD return towards their baseline values. These results emphasize
that not all types of bone and skeletal sites respond to GH therapy identically.
Furthermore a short course of GH replacement over 6-12 months may result in
significant changes in BMD several years later.
PMID- 9640414
TI - Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly
population: relation to age and sex steroid levels.
AB - BACKGROUND: Most previous studies concerning the relationship between IGF-I and
age used assays measuring total IGF-I. Although free IGF-I is considered of
greater biological relevance, little is known about its relationship with sex
steroids levels in elderly healthy subjects. MEASUREMENTS: In a cross-sectional
study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured
serum total and free IGF-I, IGFBP-1 and IGFBP3 levels and sex steroids. Free
androgen index and free oestradiol index were used as an indicator for free
oestradiol and free testosterone levels, respectively. RESULTS: Free IGF-I levels
did not decline with age in the whole study population. Free IGF-I levels even
increased in individuals above 70 years of age in comparison to those aged
between 55 and 70 years (mean +/- SE 0.106 +/- 0.007 nmol/l vs. 0.086 +/- 0.004
nmol/l, P = 0.009). Total IGF-I and IGFBP-3 decreased with age (r = -0.20, P =
0.005 and r = -0.24, P = 0.001, respectively). Total IGF-I levels were positively
related with free oestrogen index in both sexes. Free IGF-I did not relate to
free oestrogen or androgen index. In women only, free IGF-I was related
positively with DHEAS while IGFBP-1 was inversely correlated with DHEAS.
CONCLUSIONS: Free IGF-I levels do not decrease with age and are even higher in
individuals above 70 years. There was no relationship between free IGF-I and free
androgen or oestrogen index in either gender. We hypothesize that higher free IGF
I levels in older persons may be the consequence of selective survival in the
cohort: subjects with high free IGF-I levels may live longer. The absence of a
relationship between free IGF-I levels and free androgen and oestrogen indices
suggests that there is no direct interaction between the biological activity of
circulating IGF-I levels and sex hormone production in a healthy ageing
population.
PMID- 9640415
TI - Determinants of serum insulin-like growth factor I in growth hormone deficient
adults as compared to healthy subjects.
AB - OBJECTIVE: Growth hormone status is an important determinant of serum IGF-I but
it is well known that hypopituitary adults with pronounced GH-deficiency (GHDA)
may exhibit normal IGF-I levels. To elucidate possible causes of this apparent
paradox we compared the significance of putative IGF-I predictors in GHDA and
normal subjects. DESIGN: A cross-sectional study. SUBJECTS: Twenty-seven GHDA (9
females, 18 males, mean +/- SE age 44 +/- 1 years) and 27 healthy control
subjects (9 females, 18 males, mean +/- SE age 43 +/- 2 years). RESULTS: Serum
IGF-I and IGFBP-3 were significantly lower in GHDAs, but a considerable overlap
existed (IGF-I (microgram/l) 87 +/- 12 (GHDA) vs 177 +/- 10 (Control) (P <
0.001)). In both Controls and GHDA, IGF-I was higher in males than females
(Control: 196 +/- 12 vs 138 +/- (P = 0.004); GHDA: 97 +/- 16 vs 56 +/- 11 (P =
0.05)). In GHDA, males on testosterone substitution had the highest IGF-I
concentrations. The molar IGF-I:IGFBP-3 ratio was significantly lower in GHDAs
(0.18 +/- 0.01 vs 0.23 +/- 0.02 (P = 0.002)). IGFBP-1 (microgram/l) was
significantly elevated in GHDAs (6.28 +/- 1.11 vs 3.07 +/- 0.32 (P < 0.001))
despite comparable fasting insulin levels. Percentage total body fat (TBF, DEXA,
waist/hip ratio, and intra-abdominal fat (CT) were all elevated in GHDAs. IGF-I
correlated positively with lean body mass (DEXA) and negatively with TBF and
IGFBP-1 in both groups. IGF-I correlated negatively with age in CON but not in
GHDAs, whereas IGF-I correlated positively with IGFBP-3 only in GHDAs. Multiple
regression analysis revealed that age and IGFBP-1 were the only significant
predictors of IGF-I in CON, whereas IGFBP-3 and, to a lesser extent TBF, were the
only independent predictors of IGF-I in GHDAs. Neither peak stimulated GH, nor
physical fitness contributed in any equations in the two groups. CONCLUSIONS: 1)
IGF-I levels are regulated by several variables in addition to GH status 2) age
per se is an independent negative determinant in healthy subjects but not in GHDA
3) it is probable that some cases of paradoxically high IGF-I levels in GHDA are
secondary to inappropriately elevated IGFBP-3 levels. 4) in mid-adulthood males
have higher IGF-I levels than females and it is likely that testosterone directly
stimulates IGF-I. The influence of gender and sex steroids must therefore be
accounted for when comparing IGF-I levels between hypopituitary and healthy
subjects.
PMID- 9640416
TI - Serum concentrations of insulin, insulin-like growth factor(IGF)-I, IGF binding
protein (IGFBP)-1 and -3 and growth hormone binding protein in obese children:
fasting IGFBP-1 is suppressed in normoinsulinaemic obese children.
AB - OBJECTIVE: Simple obesity is characterized by normal or accelerated growth in the
presence of reduced serum levels of GH, whereas its detailed mechanism remains
unknown. We, therefore, evaluated interrelationships among serum levels of
insulin, IFG-I, IGF binding protein (IGFBP)-1 and -3 and growth hormone binding
protein (GHBP) in prepubertal obese children. SUBJECTS: Prepubertal 20 obese
children and 20 age-matched control children were included in the study. RESULTS:
Serum levels of insulin, IGF-I and IGFBP-3 in obese children did not differ from
those in controls. The serum level of IGFBP-1 was significantly lower in obese
children (22.1 +/- 18.4 micrograms/l, P < 0.001) than in control children (76.0
+/- 62.9 micrograms/l). No relationship was found between the serum levels of
insulin and IGF-I, IGFBP-1, or IGFBP-3 in obese subjects. The serum level of GHBP
in obese children was significantly elevated as compared with that in controls
and was positively correlated with body mass index (BMI). No relationship was
found between the serum levels of GHBP and IGF-I in obese subjects. CONCLUSIONS:
The present study showed for the first time that the fasting IGFBP-1 level was
suppressed in prepubertal obese children with fasting normoinsulinaemia. We
speculate that the hyperinsulinaemia which cannot be detected in the fasting
state may have suppressed hepatic production of IGFBP-1. Alternatively, the
reduced IGFBP-1 is likely to be a compensatory response to impaired insulin
sensitivity. Thus, the IGFBP-1 level may be a useful predictor for the early
identification in the development of insulin resistance in prepubertal obese
children.
PMID- 9640417
TI - Corticotroph axis sensitivity after exercise in endurance-trained athletes.
AB - OBJECTIVE: The present study was conducted in order to describe human hypothalamo
pituitary adrenal (HPA) axis adaptation in a model of repeated physical stress
(endurance training) that causes a moderate increase in cortisol levels.
SUBJECTS: We performed the same stimulation tests (adrenal stimulation with ACTH
or pituitary stimulation with combined CRH/LVP) in a population of 8 endurance
trained athletes in two distinct situations: resting (baseline cortisol values)
and 2 h after the end of strenuous exercise (increased cortisol values) to
evaluate the HPA axis sensitivity to endogenous sustained increases in cortisol
concentrations. MEASUREMENTS: During these tests, saliva and plasma cortisol (Fs
and Fp, respectively) were assessed and compared. RESULT: Cortisol values in both
plasma and saliva at the end of 2 h of exercise were significantly higher than in
rested controls: Fs 11.5 +/- 1.3 vs 6.5 +/- 0.8 nmol.l-1 and Fp 428 +/- 36 vs 279
+/- 27 nmol.l-1 (post exercise vs post rest sessions, respectively, P < 0.001 for
both). After either hormone test (CRH/LVP or ACTH), cortisol levels in plasma and
saliva increased similarly when rest was compared to post exercise. Saliva
variations (delta %) under exogenous hormone stimulation were dramatically
greater than plasma variations. For example, under ACTH stimulation, the relative
increments in cortisol were on control day: delta Fs 980 +/- 139 vs delta Fp 218
+/- 43% (saliva vs plasma, respectively, P < 0.05) and on exercise day: delta Fs
605 +/- 89 vs delta Fp 102 +/- 14% (saliva vs plasma, respectively, P < 0.05).
CONCLUSIONS: In endurance-trained athletes, displaying a moderate but sustained
endogenous cortisol increase: (1) ACTH responses following pituitary stimulation
are not blunted, (2) cortisol responses following maximal adrenal stimulation are
not blunted. Our results favour the hypothesis of a decreased pituitary
sensitivity to cortisol negative feedback whereas the hypothesis of a major
decreased adrenal sensitivity to ACTH was discarded. The greater ability of
saliva assays to detect a cortisol increase strongly supports its use in the
study of HPA physiology, whether under basal or dynamic conditions.
PMID- 9640418
TI - Overnight urinary free cortisol determination: a screening test for the diagnosis
of Cushing's syndrome.
AB - OBJECTIVE: The collection of urine over 24 h to measure free cortisol (UFC) is
used to diagnose Cushing's syndrome. However, a complete collection of urine is
not easy to achieve and the sampling is frequently inaccurate, so a 24 h
collection for the determination of UFC excretion is used as a confirmatory
rather than a screening test for Cushing's syndrome. Our objective was to
evaluate a more convenient urine collection for screening patients suspected of
Cushing's syndrome. DESIGN: We have studied the possibility of using night-time
(from 2000 h to 0800 h) UFC excretion as a screening test for Cushing's syndrome
('overnight UFC'). PATIENTS: Thirty patients with proven Cushing's syndrome were
studied before treatment (21 cases of Cushing's disease, two cases of ectopic
ACTH secretion, seven of adrenal adenoma). The results were compared to those
from 150 control obese subjects. MEASUREMENTS: Overnight UFC, and creatininuria
(UC), were evaluated at least once in the patients and in all subjects. The 24 h
UFC and UC were determined at least once in the patients and in 56 control
subjects. RESULTS: The overnight UFC/UC ratio clearly separated all but one
patient of the two groups: 194 +/- 386 vs 5.7 +/- 3.4 nmol/mumol (P < 0.0005)
(ranges 16.2-2024 vs 0.6-17.4, Cushing's syndrome vs controls, respectively). The
only patient with Cushing's syndrome who had an overnight UFC/UC ratio that
overlapped with that of controls suffered from renal failure. The 24 h UFC/UC
ratio of the patients differed from the ratio of controls: 184 +/- 365 vs 8.4 +/-
4.1 nmol/mumol (P < 0.0005) (ranges 14-1639 vs 1.5-21.2, respectively). Four
patients with Cushing's syndrome had 24 h UFC/UC ratios lower than the upper
control ratio. CONCLUSION: The overnight urinary sampling is a simple procedure
compared to the 24 h urine collection performed in out-patients. For a
sensitivity set at 100%, the specificities were 97% for the overnight UFC/UC
ratio and 87% for the 24 h-UFC/UC ratio. This therefore appears to provide a good
screening method for Cushing's syndrome.
PMID- 9640419
TI - Corticosteroid metabolism in human granulosa-lutein cells.
AB - OBJECTIVE: The aims of this study were to determine the type and level of 11 beta
hydroxysteroid dehydrogenase (11 beta HSD) in human granulosa-leutein cells (GLE)
shortly before ovulation and to correlate activity with the outcome of treatment
in patients undergoing in vitro fertilization and embryo transfer (IVF/ET).
DESIGN: GLC from 32 patients undergoing IVF/ET were tested for type and level of
11 beta HSD activity in relation to treatment outcome. PATIENTS: Periovulatory
follicles were aspirated by ultrasound guided transvaginal puncture following a
standard controlled ovarian stimulation protocol, approximately 36 h after
administering an ovulation-inducing dose of human chorionic gonadotrophin (HCG).
GLC were separated from follicular fluid by density-gradient centrifugation and
taken for measurement of 11 beta HSD activity in vitro; oocytes were used for
IVF/ET. MEASUREMENTS: Interconversion of cortisol (F) and cortisone (E), and
dexamethasone (D) and 11-dehydrodexamethasone (DHD) was measured in standardized
assays comprising incubation of GLC with 3H-labelled substrate, with separation
of substrate and product by thin-layer radiochromatography. RESULTS: Conversion
of F to E varied from 10.5 to 30.9% while that of E to F was between 2.4 and
44.6%. In the GLC of 25 patients in whom both activities were measured,
dehydrogenase (F to E) activity predominated in 13 and reductase (E to F) in 12.
By contrast, D (substrate for 11 beta HSD2 but not 11 beta HSD1) showed less than
1% metabolism in this system while DHD (substrate for 11 beta HSD1 and 11 beta
HSD2) was converted significantly (65.6-90.5%) to D in the four patients tested.
There was no significant difference in the interconversion of F and E between
patients who became pregnant and those who did not. CONCLUSIONS: The
dehydrogenase and oxoreductase reactions catalysed by 11 beta HSD both occur in
granulosa-lutein cells at the time of follicular rupture, probably due to 11 beta
HSD1. A lack of measurable conversion of dexamethasone to 11-dehydrodexamethasone
suggests that dehydrogenation due to 11 beta HSD2 is low or absent. Neither type
nor level of 11 beta HSD activity measured under the present assay conditions
correlates with IVF outcome.
PMID- 9640420
TI - Lipoprotein lipase mass and activity in post-heparin plasma from subjects with
intra-abdominal visceral fat accumulation.
AB - OBJECTIVES: The purpose of this study was to investigate the possibility of
impaired lipolysis of triglyceride-rich lipoproteins in patients with abdominal
visceral fat accumulation by assessing two major lipolytic enzymes in the plasma,
lipoprotein lipase (LPL) and hepatic lipase (HL). DESIGN AND PATIENTS: A total of
31 patients [20 men, 11 women, age 50 +/- 7 years old, body mass index (BMI) 26
+/- 2 kg/m2 (mean +/- sd)] were analyzed. Visceral fat and subcutaneous fat areas
were evaluated using a computerized tomographic (CT) method at the level of the
umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured
using Triton X-100-emulsified triolein and LPL activity was calculated as the
activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL
enzyme mass was determined by a sandwich enzyme immunoassay. RESULTS: The
visceral fat area was found to be negatively correlated with LPL mass (V vs LPL
mass, r = -0.37, P = 0.04) in PHP and had a tendency toward negative correlation
with the LPL activity in the PHP (V vs LPL activity, r = -0.29, P = 0.12).
Subcutaneous fat area, on the other hand, did not show any correlation with LPL
activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The
visceral fat area was found to be positively correlated with fasting serum
insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated
with LPL mass or activity in the PHP. Multi-regressional analysis showed that
abdominal visceral fat could be correlated with LPL mass in the PHP,
independently of fasting serum insulin. The HL activity from PHP of the patients
did not show significant correlation with visceral fat area, subcutaneous fat
area or body mass index. CONCLUSIONS: Fat distribution affects LPL mass and
activity, either directly or via another metabolic abnormality such as insulin
resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and
very low density lipoproteins (VLDL) in these subjects.
PMID- 9640421
TI - The tender neck: thyroiditis or thyroid abscess?
AB - Following apparent subacute thyroiditis, a 16-year-old girl developed a left
thyroid abscess thought to be secondary to steroids and haematogenous spread from
a pilonidal abscess. The thyroid suppuration became recurrent and required
partial thyroidectomy. Further left-sided abscess formation in the neck prompted
a barium swallow which revealed the source of infection to be a sinus tract
arising from the left piriform fossa. The patent fourth branchial sinus tract was
later excised. All patients with a tender thyroid should have ultrasound-guided
fine needle aspiration to establish the diagnosis. If suppuration is confirmed, a
barium swallow is advised to exclude a sinus tract from the piriform fossa.
PMID- 9640422
TI - Altered lipid pattern explains increased cardiovascular mortality in
hypopituitary patients with growth hormone deficiency.
PMID- 9640423
TI - Transient hypothyroidism after iodine-131 therapy for Graves' disease.
PMID- 9640424
TI - Retinoid X receptor gamma mRNA expression is reduced in recurrent non-functioning
pituitary adenomas.
PMID- 9640425
TI - Voluntary and involuntary access to autobiographical memory.
AB - Involuntary autobiographical memories recorded in a diary study are compared to
voluntary autobiographical memories retrieved in response to verbal cues in a
laboratory. The verbal cues were generated to be comparable to the cues that were
found to elicit the involuntary memories. The findings demonstrate that voluntary
and involuntary retrieval may access different samples of autobiographical
memories. The voluntary memories were (1) less specific, (2) more frequently
rehearsed, and (3) less emotionally positive than the involuntary memories. A
reanalysis of the diary study examined conditions of involuntary retrieval. The
memories occurred most frequently when attention was diffuse. They were typically
triggered by environmental cues matching central features of the remembered
event. The findings are discussed in relation to current models of
autobiographical memory.
PMID- 9640426
TI - Memory span, naming speed, and memory strategies in poor and normal readers.
AB - Eleven-year-old severely impaired poor readers failed to show a word length
effect with pictorial presentation, but showed an effect of equal magnitude to
that of reading age and chronological age controls with auditory presentation.
The lack of a pictorial word length effect was unlikely to be due to slow speed
of naming skills, as in one study these were at least as fast as those of the
reading age controls. It is possible that the poor readers failed to verbally
encode the pictures. However, they reported using verbal rehearsal, and lip
movements were often observed during presentation, suggesting that they did
verbally encode the items. Therefore they may have failed to show a word length
effect because they did not retrieve information from the phonological store at
recall. Although the poor readers had impaired naming speed skills for their age
on both discrete item identification and articulation rate tasks, they could not
be equated with their chronological age controls on memory span or reading when
these naming speed differences were controlled. However, the groups were matched
on the naming speed measures when differences in reading ability were controlled.
PMID- 9640427
TI - When even arbitrary order becomes important: developments in reliable temporal
sequencing of arbitrarily ordered events.
AB - By late in the first year of life, children show temporally ordered recall of
event sequences, the orders of which are constrained by enabling relations; they
do not reliably recall arbitrarily ordered events. Using elicited imitation, in
two experiments, we examined age- and experience-related changes in young
children's recall of events, the orders of which are arbitrary. The changes were
found to have implications for the efficacy of verbal reminding and to be related
to developments in language. Specifically, on the basis of a single experience,
16-month-olds did not accurately recall arbitrarily ordered event sequences
either immediately or after a two-week delay (Experiment 1); 22-month-olds
recalled the events immediately, but not after the delay; by 28 months, children
recalled the events even after the delay (Experiment 2A). This development was
accompanied by changes in the ability to benefit from verbal reminders: 28-month
olds' recall was facilitated by provision of verbal reminders, whereas that of
the younger children was not. Moreover, age-related changes in accurate
reproduction of lengthy arbitrarily ordered event sequences were found to be
related to developments in language (Experiment 2B). Critically, the limitations
on 1-year-olds' performance that are overcome with age are not absolute: After
three experiences, 16-month-olds accurately recalled the events after a two-week
delay; their recall was facilitated by verbal reminders (Experiment 1). The
implications of these findings are discussed.
PMID- 9640428
TI - Descriptiveness and proper name retrieval.
AB - Cohen (1990) hypothesised that the retrieval of proper names is particularly
difficult because proper names convey little information about their bearers'
attributes. In the present study, this hypothesis was evaluated by using a face
naming task. Faces were those of cartoon and comic-strip characters bearing
either arbitrary names or descriptive names. Results unequivocally showed that
retrieval blocks occurred more often in naming characters bearing arbitrary names
than in naming characters bearing descriptive names. Moreover, retrieving
arbitrary names that were also common names was as difficult as retrieving
arbitrary names that were not common names. These results support Cohen's claim
that arbitrariness plays a significant role in the relative vulnerability of
proper name retrieval.
PMID- 9640429
TI - Contextual dependencies during perceptual-motor skill performance: influence of
task difficulty.
AB - The present experiment was designed to address the role of task difficulty for
the development of contextual-dependent behaviour during perceptual-motor task
acquisition. Task difficulty in the present study was manipulated by restricting
the time that the subject; (a) viewed task-relevant information, and (b) was
afforded to execute a sequence of key presses. Assuming these manipulations made
the acquisition of the key press tasks more difficult, it was hypothesised that
reducing the time for either of these processes would result in a greater
dependence on reinstating the training context at the time of test. This was
based on previous findings reported by Wright and Shea (1991) which indicated
that task difficulty can contribute to the development of context-dependent
behaviour. The results of the study revealed that viewing time was a potent
difficulty manipulation. This is supported by the slower acquisition rates for
subjects exposed to short as opposed to long viewing conditions during training.
More importantly, the impact of changing the intentional-incidental stimuli
relationship that was apparent during training, during the test was greatest for
the individuals who experienced shorter viewing times during the training phase.
Thus, the proposed influence of task difficulty on contextual-dependent
performance was supported. This dependency was manifested as a slowing in both
the initiation and execution of the correct key presses. It is proposed that
individuals trained in the more difficult viewing condition during training, when
faced with an incongruence in the acquisition and test stimuli, must engage
additional data-driven verification processes to supplement their extant
knowledge in order to execute an appropriate response.
PMID- 9640430
TI - Individual differences and the creation of false childhood memories.
AB - We investigated if college students will create false childhood memories, the
role of self-knowledge in memory creation, and if there are reliable individual
differences related to memory creation. Based on information obtained from
parents, we asked college students about several true childhood experiences. We
also asked each student about one false event and presented the false event as if
it was based on parent information. We asked the students to describe all events
in two interviews separated by one day. When participants could not recall an
event (whether true or false), we encouraged them to think about related self
knowledge and to try to imagine the event. In an unrelated experimental session,
the students were administered four cognitive/personality scales: the Creative
Imagination Scale (CIS), the Tellegen Absorption Scale (TAS), the Dissociative
Experiences Scale (DES), and the Marlowe-Crowne Social Desirability Scale (SDS).
We found that approximately 25% of the students created false childhood memories.
Participants who made connections to related self-knowledge in the first
interview were more likely to create false memories. We also found that the CIS
and the DES were positively related to memory creation. Factors that decrease
one's ability to engage in reality monitoring are related to the acceptance of
false events and the creation of false memories.
PMID- 9640431
TI - Rehabilitation of memory for people's names.
AB - In a training study, memory-impaired patients were taught strategies to improve
the learning of new names and the retrieval of familiar people's names. To
improve new name learning, the patients were encouraged to give more meaning to a
person's name, without requiring an explicit association between the face and the
name. Strategies to improve retrieval of familiar names mainly concerned ways to
resolve tip-of-the-tongue states. Learning names to faces improved following
training on one of the two target tests and this improvement was maintained six
months following training. Retrieval of familiar people's names also improved
immediately following the training, although the improvement disappeared at the
six-month follow-up. Two control memory tests and a group of normal subjects, who
received no training, were used to discriminate an effect of training from the
effects of repeated testing and the extensive attention received by the trained
group.
PMID- 9640432
TI - The spacing effect depends on an encoding deficit, retrieval, and time in working
memory: evidence from once-presented words.
AB - The spacing effect in list learning occurs because identical massed items suffer
encoding deficits and because spaced items benefit from retrieval and increased
time in working memory. Requiring the retrieval of identical items produced a
spacing effect for recall and recognition, both for intentional and incidental
learning. Not requiring retrieval produced spacing only for intentional learning
because intentional learning encourages retrieval. Once-presented words provided
baselines for these effects. Next, massed and spaced word pairs were judged for
matches on their first three letters, forcing retrieval. The words were not
identical, so there was no encoding deficit. Retrieval could and did cause
spacing only for the first word of each pair; time in working memory, only for
the second.
PMID- 9640433
TI - Apperception and imagery in blindfold chess.
AB - Apperception constructs functional and "meaningful" mental representations. These
representations are often built on mental images. Hence it is rational to assume
that the contents of some parts of images may be functionally more important than
others. This means that the cognitive processing of some parts of the image is
more effective than for others. To extract this preferential structure, which we
call the functional figure in mental images, five experiments were conducted on
blindfold chess imagery. We showed that blindfold chess players have much better
recall of functionally significant than of functionally insignificant areas of
chess positions. Thus, of the various mental representations of chess board
areas, the functionally more significant areas are better represented than
others.
PMID- 9640434
TI - Visuo-spatial imagery in congenitally totally blind people.
AB - The present study provides evidence for congenitally blind people's ability to
generate visuo-spatial images, and explores its limitations. Congenitally blind
and sighted participants were asked to memorize the spatial positions of target
objects (cubes) in two- and three-dimensional matrices, while simultaneously
performing a sequence of spatially based imagery operations. Furthermore, during
half of the trials, subjects were required to perform an articulatory suppression
task. Although articulatory suppression affected both groups to the same extent,
congenitally blind people performed poorly with more demanding spatial tasks and
when an active elaboration was required.
PMID- 9640435
TI - Knowledge of the crime context: improving the understanding of why the cognitive
interview works.
AB - Since the Cognitive Interview (CI) was devised under laboratory conditions
(Geiselman, Fisher, MacKinnon, & Holland, 1985), researchers have performed many
experiments where a variety of variables and conditions have been reported.
Nevertheless, few studies have attempted to delve into the theoretical aspects on
which the CI is based. A variable that might help us to improve our understanding
of why the CI works is prior knowledge of the crime context. Some studies have
included familiar contexts and others unfamiliar ones, but no study has been
performed to test the effect of the familiarity of the crime context as an
independent variable. The aim of this research is to study the effect of prior
knowledge on subjects' memory when they are interviewed by means of the CI in
contrast to a Spanish Standard Interview (SSI). A significant effect of prior
knowledge that subjects had of the context where the crime took place was
expected, especially for those subjects who were interviewed by means of the CI.
Results confirmed this hypothesis.
PMID- 9640436
TI - Diabetic retinopathy.
AB - Diabetic retinopathy is the commonest cause of blindness amongst individuals of
working age. The onset of retinopathy is variable. Regular ophthalmic screening
is essential in order to detect treatable lesions early. Retinal laser therapy is
highly effective in slowing the progression of retinopathy and in preventing
blindness. As the sufferers of diabetes mellitus, the commonest endocrine
disorder, now constitute approximately 1-2% of Western populations, concerted
multidisciplinary effort must be made towards cost-effective community screening
by the medical community.
PMID- 9640437
TI - Disorders of the sleep-wake cycle in adults.
AB - Adults have an intrinsic body clock which regulates a complex series of rhythms
including sleep and wakefulness, fatigue and cognitive ability. This endogenous
clock naturally runs more slowly than the solar day and is entrained to a 24-h
rhythm primarily by the alternation of light and darkness. Jet lag, shift-work
sleep disorder, and some of the chronic insomnias are caused by a temporal
discrepancy of the body clock relative to the surrounding environment and social
network. The underlying mechanisms and general management are described. Both
bright light and melatonin therapy have potential in the management of these
disorders. Traditionally, bright light therapy has been used to alleviate the
depression associated with seasonal affective disorder. Melatonin has received
much ill-formed publicity, it being claimed that it is a panacea and an
'antiageing' treatment. Both of these treatment approaches are reviewed.
PMID- 9640438
TI - Thymectomy for myasthenia gravis.
AB - The pathophysiological role of the thymus in myasthenia gravis, and the mechanism
of therapeutic effect of thymectomy, are incompletely understood. Nevertheless,
thymectomy is a valuable treatment modality in selected patients with generalised
myasthenia gravis. There are several types of thymectomy operation, but no one
operative approach is clearly superior to the others. Total removal of the thymus
gland is essential. Additional excision of associated mediastinal and cervical
tissue, that may harbor ectopic thymic rests, is a controversial surgical issue.
Surgeons that advocate thymectomy through small, cosmetically favourable,
incisions usually believe that simple removal of the thymus gland is an adequate
operation. Surgeons that emphasise the importance of removing extrathymic tissue,
in addition to the thymus gland, usually favour greater operative exposure
through a median sternotomy. To minimise operative morbidity, surgery for
myasthenia gravis requires a multidisciplinary (neurology, surgery, anaesthesia)
approach to peri-operative care.
PMID- 9640440
TI - Advance directives and living wills.
AB - Under certain circumstances, living wills or advance directives may carry legal
force in the UK. This paper traces the development of advance directives,
clarifies their current legal position and discusses potential problems with
their use. Case histories are used to illustrate some of the common dilemmas
which doctors may face.
PMID- 9640441
TI - Recognition and management of hypercholesterolaemia in patients awaiting elective
coronary artery bypass grafting.
AB - The recently published Scandinavian Simvastatin Survival Study showed that long
term treatment with simvastatin, in patients with ischaemic heart disease and
serum cholesterol levels between 5.5 and 8.0 mmol/l, improved survival. The
present study was conducted in order to evaluate whether patients with ischaemic
heart disease awaiting coronary revascularisation are aware of their serum
cholesterol levels and whether raised levels are being treated adequately. One
hundred consecutive patients admitted from our waiting list for elective coronary
artery bypass grafting, with or without valve replacement, were included in the
study. The patients were asked whether they had a history of raised serum
cholesterol and, if so, how this was being treated. Fasting serum cholesterol
levels were subsequently taken in the morning before surgery. Forty-six patients
gave a positive history of raised blood cholesterol levels; 25 of these were on
cholesterol-lowering medication at the time of admission, 15 were on a lipid
lowering diet and six were not being treated. Thirty-one (67%) of these 46
patients had a serum cholesterol of more than 5.5 mmol/l, compared with 30 (56%)
of the 54 patients without a positive history of hypercholesterolaemia, and 61%
of the total 100 patients. These data suggest that an inadequate number of
patients awaiting coronary artery bypass grafting are aware of their cholesterol
status. The management of hypercholesterolaemia among these patients could be
improved.
PMID- 9640439
TI - Trends in the management of gastro-oesophageal reflux disease.
AB - Gastro-oesophageal reflux disease is common, with up to 10% of the general
population experiencing heartburn on a daily basis. It is a chronic condition and
follow-up studies indicate the presence of symptoms at least 20 years after
initial diagnosis. In addition to lifestyle modifications, management usually
involves the use of an acid suppressant from the H2-receptor antagonist or proton
pump inhibitor groups or a prokinetic agent at some stage. In terms of initial
symptom resolution and mucosal healing the proton pump inhibitors are
consistently superior to the other available agents. However, while it is
possible to keep the majority of patients in remission while taking medications,
almost all patients have a recurrence of symptoms within six months of stopping
medications. The introduction of laparoscopic fundoplication has produced
promising initial results but the long-term benefits of this procedure remain to
be established. The role of Helicobacter pylori eradication in the management of
gastro-oesophageal reflux disease needs further evaluation.
PMID- 9640442
TI - Variability in management of symptomless microhaematuria in schoolchildren.
AB - The evaluation of incidentally detected symptomless microhaematuria in
schoolchildren is controversial. Some authors advocate varying numbers of
immediate tests, while others recommend investigations only in cases who develop
systemic symptoms or signs, or a decline in renal function. The objective of this
study was to estimate the extent to which this uncertainty affects the declared
habits of practising physicians. A sample of 16 family physicians, 42 primary
care paediatricians and 26 full-time hospital-based paediatric nephrologists in
Israel were asked to complete a survey using a written case of a hypothetical
eight-year-old boy with incidentally detected symptomless microhaematuria.
Responses were received from 16 (100%), 18 (43%) and 18 (69%), respectively. The
mean number of requested tests, other than follow-up examination of the urine,
were 1.5 (range 0-5) for family physicians, 2.5 (1-5) for primary care
paediatricians and 5.3 (2-12) for paediatric nephrologists, at an average cost of
NIS 408 (US$ 136), NIS 454 (US$ 151) and NIS 860 (US$ 286), respectively. There
was also a marked variability within subspecialty groups, so that some family
physicians recommended more tests at a higher cost than some of the paediatric
nephrologists. There was a marked and unexplained variability within and among
the three groups of respondents regarding the extent of the evaluation. The main
reason for this variability is probably the uncertainty about the scientifically
appropriate way to approach this condition in a symptomless child.
PMID- 9640443
TI - A collaborative audit of the management of hypertension in general practice.
AB - We carried out an audit of the management of essential hypertension in general
practice, against standards based on current guidelines. We examined the records
of 882 hypertensive subjects (on medication) in whom hypertension had been
diagnosed between January 1989 and December 1993, from 14 general practices in
the Portsmouth and South East Hampshire Health Authority. The overall prevalence
of hypertension was 3.5%. Pretreatment blood pressure had been measured on three
or more occasions in 87% of patients. Pretreatment blood pressure was equal to or
greater than 150/95 mmHg in 96% and 160/100 mmHg in 86.5% of patients. A thiazide
diuretic was the initial drug of choice in 30% of patients, with beta-blockers
being the most popular initial treatment. Ninety per cent of patients had had
their blood pressure measured at least once during the preceding year. In 82.5%
of patients, current blood pressure was less than 150/95 mmHg, while 44% achieved
a current blood pressure less than 140/90 mmHg. We conclude that the prevalence
of hypertension in this population was lower than expected, suggesting the need
for improved screening. We also propose that the initial treatment choice should
be a thiazide in the majority, which would result in significant cost saving. The
blood pressure control was suboptimal compared to current guidelines.
PMID- 9640444
TI - Lymphogranuloma venereum as a cause of rectal strictures.
AB - Rectal strictures are uncommon in young patients without a history of malignancy,
inflammatory bowel disease or previous surgery. Lymphogranuloma venereum of the
rectum has been described as a rare cause of rectal strictures in the western
world, mainly in homosexual men and in blacks. It presents with nonspecific
symptoms, rectal ulcer, proctitis, anal fissures, abscesses and rectal
strictures. Clinical and endoscopic findings as well as histology resemble
Crohn's disease, which may be misdiagnosed. Serology is often positive for
Chlamydia trachomatis but negative serology is not uncommon. We present two young
black women who suffered from chronic diarrhoea, abdominal pain and weight loss.
There was no previous history and investigations showed in both cases a long
rectal stricture. Serology was positive in one patient. They were treated with
erythromycin and azithromycin and they both underwent an anterior resection of
the rectum. Postoperative histology confirmed the presence of lymphogranuloma
venereum of the rectum. We conclude that rectal lymphogranuloma venereum is a
rare cause of rectal strictures but surgeons should be aware of its existence and
include it in the differential diagnosis of unexplained strictures in high-risk
patients.
PMID- 9640445
TI - Giant cell arteritis presenting as renal vasculitis.
AB - Giant cell arteritis commonly presents with headache, polymyalgia, and visual
signs and symptoms. Other neurological, respiratory or vascular symptoms occur in
10-30% of patients. It is extremely rare for giant cell arteritis to present
initially with haematuria. Here we describe a case which presented with fever and
haematuria, which emphasise the need to be vigilant about the diagnosis of giant
cell arteritis as an underlying cause.
PMID- 9640446
TI - Sarcoidosis of the paranasal sinuses treated with hydroxychloroquine.
AB - A case of sarcoidosis of the paranasal sinuses is reported. Biopsies of the sinus
mucosa showed typical noncaseating granulomas. Hydroxychloroquine, which is known
to be active on the cutaneous form of sarcoidosis, was used here with success and
is proposed as an effective alternative to high-dose systemic steroids.
PMID- 9640447
TI - A rare abdominal cystic mass with unusual presentation.
PMID- 9640448
TI - An unusual cause for a painful diplopia.
PMID- 9640449
TI - Spontaneous intercostal bulge.
PMID- 9640451
TI - Abdominal pain in a healthy young man.
PMID- 9640450
TI - Mycobacterial liver abscess in a patient with AIDS.
PMID- 9640452
TI - An 88-year-old woman with tetraparesis after a fall.
PMID- 9640453
TI - An unusual abdominal mass.
PMID- 9640454
TI - Acute psychosis in a trauma patient due to ciprofloxacin.
PMID- 9640455
TI - Bacterial endocarditis.
PMID- 9640456
TI - Perforated diverticulitis following extra-abdominal surgery.
PMID- 9640457
TI - Role of lipid metabolites in the signalling and activation of macrophage cells by
lipopolysaccharide.
PMID- 9640458
TI - Chemistry and functional distribution of sulfoglycolipids.
PMID- 9640459
TI - Oregon groups devise rules, policies on assisted suicide.
PMID- 9640460
TI - Medicaid to pay Mississippi pharmacists for disease management.
PMID- 9640461
TI - FDA proposes rules for health claims on dietary supplements.
PMID- 9640462
TI - Immediate use of anticoagulants may not improve stroke outcomes.
PMID- 9640464
TI - Teen smoking up one third.
PMID- 9640463
TI - Integrated systems may have economic incentive for using alteplase in stroke
patients.
PMID- 9640465
TI - Herbals and homeopathic remedies as formulary items?
PMID- 9640466
TI - Outcomes of antiemetic therapy after the administration of high-dose
antineoplastic agents.
AB - Patterns of antiemetic therapy and its outcomes in patients undergoing high-dose
antineoplastic therapy were studied. The study, conducted at a cancer center,
included both a retrospective evaluation of patients undergoing highly emetogenic
high-dose chemotherapy with peripheral blood stem-cell rescue between November
1994 and December 1995 and a concurrent evaluation of patients treated between
January and May 1996. During the study period the recommended antiemetic regimen
for highly emetogenic chemotherapy was a single dose of granisetron 1 mg i.v.
daily 30 minutes before treatment on days of chemotherapy. Severity of nausea and
vomiting during both the acute phase (from day 1 of chemotherapy to 24 hours
after its completion) and delayed phase (from 24 hours to five days after the end
of chemotherapy) was graded according to the Common Toxicity Criteria Grading
Scale. A total of 59 patients were evaluable; 41 were reviewed retrospectively,
and 18 were reviewed concurrently. On day 1 of the acute phase, 53 patients (90%)
had no vomiting and 51 patients (86%) had no nausea. The frequency and severity
of nausea and vomiting increased on successive acute-phase days, and it was
necessary to add other antiemetics. Nausea and vomiting continued to be
significant problems throughout the delayed phase; 32 (54%) of the patients had a
maximum of grade 3 nausea, and 29 patients (49%) had a maximum of grade 2
vomiting. Substantial numbers of patients who received selective serotonin type 3
receptor antagonists before high-dose antineoplastic agents had significant
nausea and vomiting that required the addition of other antiemetics.
PMID- 9640467
TI - Effect of a pharmacist-education initiative on ketorolac use and costs in a
Medicaid program.
AB - The effects of a pharmacist-education initiative on the use and costs of
ketorolac in a state Medicaid program are reviewed. An intervention letter
describing changes in the manufacturer's prescribing guidelines for ketorolac and
providing suggestions for interacting with physicians regarding the use of
ketorolac was sent to 150 of the 301 pharmacies that participate in New Mexico's
Medicaid program. The remaining 151 pharmacies served as a control group.
Ketorolac claims records for three months before and after the intervention were
reviewed. The mean quantity of ketorolac tablets, total days' supply, and number
of prescriptions filled per pharmacy per month were calculated for both periods.
The number of prescriptions not filled as a result of the intervention as well as
the number that could have been avoided, the number of cases of peptic ulceration
(ketorolac's major adverse effect) that would be avoided, and the associated cost
savings if all the state's Medicaid pharmacies had been included in the
intervention were estimated. A total of 167 pharmacies (90 intervention and 77
control) dispensed ketorolac for Medicaid patients during the study period.
Ketorolac dispensing rates declined during the postintervention period in both
the intervention group and the control group, but the reduction was greater in
the intervention group. It was predicted that if all pharmacies were included in
an intervention, 135.6 fewer prescriptions for ketorolac would be filled each
year; as a result, 1.14 cases of peptic ulceration would be avoided and net
Medicaid costs would be reduced by $1638. Sending educational letters to
pharmacists was associated with a modest reduction in ketorolac use in a state
Medicaid program; a net reduction in Medicaid costs if the intervention were
extended to all pharmacies that participate in the state's Medicaid program was
projected.
PMID- 9640468
TI - Motivations and practice-area preferences of pharmacists interested in pursuing a
Pharm.D. degree through a nontraditional program.
AB - Pharmacists' interest in a proposed nontraditional Pharm.D. program, motivations
for wanting to pursue a Pharm.D. degree, and practice-area preferences were
surveyed. Questionnaires were mailed to 12,621 pharmacists in Illinois and
Arizona. Information sought included current position and practice area, number
of job and career changes, preferred practice area, and interest in enrolling in
a proposed nontraditional Pharm.D. program described in a cover letter. For
pharmacists indicating an interest, information was sought on motivations for
wanting to pursue a Pharm.D. degree expected support from employers, and
preferred practice areas after obtaining a Pharm.D. degree. The response rate was
28.8%. A total of 1119 respondents (31.9%) indicated that they would or probably
would enroll in the proposed Pharm.D. program. These pharmacists gave improving
their clinical skills and improving the quality of their work as reasons for
wanting to enroll, and half indicated that their current practice area would be
their preferred area after they completed a Pharm.D. degree. Almost three
quarters (72%) of hospital pharmacists; more than 60% of home health care or
consultant independent, and managed care pharmacists; and 21% of pharmacists in
chain pharmacies stated a preference to stay in their current practice area after
obtaining a Pharm.D. degree. Eight variables were useful in predicting whether
respondents would prefer to remain in their current practice area, including
tuition assistance or reimbursement from employers, satisfaction with current
position, and number of years in current position. Respondents who were
interested in pursuing a Pharm.D. degree through the nontraditional program
described to them were motivated by a desire to improve their clinical skills and
the quality of their work and the opportunity to open doors to new careers.
PMID- 9640469
TI - Effect of sodium metabisulfite on hydrogen peroxide production in light-exposed
pediatric parenteral amino acid solutions.
AB - The effect of sodium metabisulfite (MBS) on hydrogen peroxide (HP) production in
model and commercial amino acid solutions exposed to phototherapy light was
studied. Model and commercial pediatric amino acid solutions were prepared such
that the amino acid concentration was 1%. MBS concentration, riboflavin
concentration, and duration of exposure to phototherapy light were varied to
determine the effect on HP production. Control solutions were kept in the dark.
HP production was assayed in the model amino acid solutions by using potassium
iodide in the presence of ammonium molybdate. In all experiments, HP production
was measured at 360 nm in the presence and absence of catalase. In light-exposed
solutions, HP production increased linearly for several hours and reached a
plateau by eight hours. A mean maximum of 940 microM was produced (data pooled
for all solutions). No detectable HP was generated in the solutions kept in the
dark. After two hours of light exposure, it was necessary to add at least 10
times more MBS than is typically found in commercial total parenteral nutrient
solutions to scavenge all the HP produced. An average of up to 940 microM of HP
was produced in model and commercial pediatric parenteral 1% amino acid solutions
in the presence of phototherapy light and clinically relevant concentrations of
riboflavin and MBS. Light exposure decreased the antioxidant effect of MBS.
PMID- 9640470
TI - Pharmacy coordination of an indigent care program in a psychiatric facility.
PMID- 9640471
TI - Activity of enoxaparin sodium in tuberculin syringes for 10 days.
PMID- 9640472
TI - Content uniformity and stability of nifedipine in extemporaneously compounded
oral powders.
PMID- 9640473
TI - Institutional and contingency approaches to the reprofessionalization of
pharmacy.
PMID- 9640474
TI - Therapeutic drug monitoring: observations and recommendations.
PMID- 9640475
TI - Workshop for developing drug formularies in Russia.
PMID- 9640476
TI - Filtration recommendations for i.v. medications.
PMID- 9640477
TI - Fluorouracil precipitate.
PMID- 9640478
TI - Fluorouracil precipitate.
PMID- 9640479
TI - Comparison of tacrolimus absorption in transplant patients receiving continuous
versus interrupted enteral nutritional feeding.
AB - OBJECTIVE: To determine the effect of enteral nutritional feeding on the
absorption of tacrolimus administered through a nasoduodenal tube to organ
transplant patients. METHODS: A nonrandomized, prospective study of tacrolimus
absorption was performed in 10 liver or lung transplant patients who received
Osmolite enteral nutrition through a nasoduodenal feeding tube. Multiple blood
samples were collected just prior to and at 30 minutes, 1, 2, 3, 4, 6, 8, 10, and
12 hours after nasoduodenal administration of tacrolimus on 2 consecutive days,
once when tacrolimus was administered along with the continuous enteral feeding
and the other time when the enteral feeding was withheld 1 hour prior to and 8
hours after tacrolimus administration, to assess tacrolimus absorption. The whole
blood tacrolimus concentrations were measured by the microparticulate enzyme
immunoassay method. Pharmacokinetic parameters between the two time periods were
compared by using a paired t-test at a significance level of a p value of 0.05 or
less. RESULTS: The time to reach peak blood concentrations (p = 0.055), dose
normalized trough concentrations (p = 0.617), maximum blood concentrations (p =
0.197), and dose-normalized AUC (p = 0.755) were not significantly different
between two study periods. CONCLUSIONS: This study demonstrated that simultaneous
administration of Osmolite enteral feedings with tacrolimus did not interfere
with tacrolimus absorption in transplant patients.
PMID- 9640480
TI - Management of patients with type 2 diabetes by pharmacists in primary care
clinics.
AB - OBJECTIVE: To determine the impact of clinical pharmacists involved in direct
patient care on the glycemic control of patients with type 2 diabetes mellitus.
DESIGN: Eligible patients included those with type 2 diabetes who received
insulin or were initiated on insulin therapy by the pharmacists and were willing
to perform self-monitoring of blood glucose. The pharmacists provided diabetes
education, medication counseling, monitoring, and insulin initiation and/or
adjustments. All initial patient interactions with the pharmacists were face-to
face. Thereafter, patient-pharmacist interactions were either face-to-face or
telephone contacts. SETTING: Two primary care clinics in a university-affiliated
Veterans Affairs Medical Center. PARTICIPANTS: Study subjects were patients with
type 2 diabetes who were referred to the pharmacists by their primary care
providers for better glycemic control. OUTCOME MEASURES: Primary outcome
variables were changes from baseline in glycosylated hemoglobin, fasting blood
glucose, and random blood glucose measurements. Secondary outcomes were the
number and severity of symptomatic episodes of hypoglycemia, and the number of
emergency room visits or hospitalizations related to diabetes. Twenty-three
veterans aged 65-9.4 years completed the study. Fifteen (65%) patients were
initiated on insulin by the pharmacists; 8 (35%) were already using insulin.
Patients were followed for a mean-SD of 27-10 weeks. Glycosylated hemoglobin,
fasting blood glucose concentrations, and random blood glucose concentrations
significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01),
and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes
occurred in 35% of patients. None of these episodes required physician
intervention. CONCLUSIONS: This study demonstrates that pharmacists working as
members of interdisciplinary primary care teams can positively impact glycemic
control in patients with type 2 diabetes requiring insulin.
PMID- 9640481
TI - State pharmacy regulators' opinions on regulating pharmaceutical care outcomes.
AB - OBJECTIVE: To examine the opinions of state pharmacy regulators regarding
responsibility for the outcomes of drug therapy, and approaches that might be
taken to regulate for pharmaceutical care outcomes. DESIGN: Surveys were sent to
the executive secretaries of state pharmacy boards. The executive secretaries
were encouraged to seek input from other board staff and board members in
formulating a response. Reminder postcards were sent to all subjects 1 week after
the initial mailing. MEASURES: The survey instrument was divided into three
sections. The first section identified 10 approaches that state boards could use
to regulate for outcomes and asked subjects to indicate the utility of each. The
second and third sections asked the subjects to determine the extent to which
pharmacies and pharmacists, respectively, should be responsible for outcomes
potentially related to pharmaceutical care. RESULTS: Forty-one usable surveys
were returned. All approaches to regulation were viewed as potentially useful,
and scores for three approaches indicated that they would be consistently helpful
for effective regulation of pharmaceutical care outcomes. The pharmacy was viewed
as solely responsible for poor outcomes related to systems deficiencies, a lack
of self-assessment, inadequate references, equipment, and technician support.
Pharmacists were assigned greatest responsibility for outcomes related to
prescription filling, and less responsibility for outcomes related to patient
care. However, there was considerable variation in responses to many of the
items, reflecting the diverse opinions of pharmacy regulators on these issues.
CONCLUSIONS: While pharmacy regulators appear open to some outcomes-oriented
approaches to regulation, there is no clear consensus on responsibility for
pharmaceutical care outcomes.
PMID- 9640482
TI - Syncopal episodes associated with cisapride and concurrent drugs.
AB - OBJECTIVE: To report a case of QT prolongation and syncopal episodes resulting
from concomitant use of cisapride and agents known to inhibit its metabolism.
CASE SUMMARY: A 53-year-old white woman was involved in two motor vehicle
accidents on the same day after experiencing syncopal episodes. Cardiac and
neurologic evaluations were negative; the syncopal episodes were attributed to QT
prolongation associated with the concomitant use of cisapride and agents known to
inhibit its metabolism. DISCUSSION: This is the first case published in the
English-language literature describing QT prolongation resulting from the
concomitant use of cisapride and agents known to inhibit its metabolism.
Clarithromycin inhibits CYP3A4, the isoenzyme responsible for the metabolism of
cisapride. Concomitant administration of cisapride with agents known to inhibit
CYP3A4 (i.e., azole antifungals, erythromycin, clarithromycin) may result in
elevated cisapride concentrations. Elevated cisapride concentrations have been
associated with QT prolongation, syncopal episodes, and cardiac dysrhythmias.
CONCLUSIONS: Acquired QT prolongation is a well-recognized adverse effect of
several drugs. Recognition of newer drugs and drug combinations that place
patients at risk for this potentially fatal adverse event is imperative for
appropriate monitoring and prevention.
PMID- 9640483
TI - Cutaneous ulceration: an unusual sign of methotrexate toxicity--first report in a
patient without psoriasis.
AB - OBJECTIVE: To describe a case of skin ulcer related to methotrexate toxicity.
CASE SUMMARY: A 67-year-old white man with seronegative arthralgia developed
recurrent skin ulcer concurrent with 3-year treatment with methotrexate 5 mg
daily. The skin ulcer resolved on discontinuation of methotrexate. DISCUSSION: To
the best of our knowledge, this is the first reported case of skin ulcer believed
to be induced by methotrexate in a patient without psoriasis. CONCLUSIONS: Skin
ulceration should be added to the list of possible toxic adverse effects of
methotrexate, not only in psoriatic patients but also in those without psoriasis.
PMID- 9640484
TI - Respiratory depression following administration of intrathecal bupivacaine to an
opioid-dependent patient.
AB - OBJECTIVE: To document two cases of respiratory depression in patients receiving
morphine once the stimulating effect of pain on respiration was removed by
bupivacaine. CASE SUMMARIES: Case 1: A 72-year-old 84-kg white man with cancer of
the bladder and bone metastases had intense back and leg pain that was treated
with intrathecal morphine for 6 months at an increasing dosage up to 10 mg twice
daily. The intrathecal route was avoided for 4 days because of a suspected local
infection at the site of the intrathecal catheter. During this 4-day period the
patient received extended-release morphine and subcutaneous morphine daily. When
the intrathecal route was used again, he received an identical dose of morphine
plus bupivacaine and epinephrine. Ten minutes after the injection, fatal
respiratory distress occurred. Case 2: A 92-year-old white woman was admitted for
revascularization of arteritis on her left leg. To treat a painful sacrum and
heel bedsores, she received extended-release oral morphine for 8 days. Induction
of the intrathecal anesthesia was performed with bupivacaine. After 10 minutes,
the patient became subcomatose, with miosis and apnea. Intravenous naloxone
restored spontaneous respiration and normal consciousness. CONCLUSIONS: Pain is a
physiologic antagonist of the respiratory depressant effects of opioid
analgesics. By reducing pain stimulation, bupivacaine may make patients more
susceptible to opioid respiratory depression. Such situations require titration
of bupivacaine and other analgesics as well as increased monitoring of the
patient.
PMID- 9640485
TI - Probable diltiazem-induced acute interstitial nephritis.
AB - OBJECTIVE: To describe a case of acute interstitial nephritis (AIN) probably
related to administration of diltiazem. CASE SUMMARY: A 53-year-old white man
presented to the hospital experiencing abdominal pain radiating to both renal
fossae, as well as dysuria. Diltiazem and atenolol had been prescribed to treat
an episode of precordial pain associated with effort. An erythematous
maculopapular rash developed approximately 2 hours after administration of a
single dose of diltiazem, and acute renal failure, associated with elevated liver
function test results, developed 6 days later. DISCUSSION: To the best of our
knowledge, this is the third reported case of acute renal failure believed to be
induced by diltiazem. In all cases, there was an obvious temporal relationship
between administration of diltiazem and the onset of acute renal failure.
Previous reports failed to discuss a probable pathogenic mechanism. AIN is the
most likely etiology of acute renal failure in our patient. Favorable resolution
with no relapse, the presence of the skin rash, and the liver sequelae suggest a
common immunoallergic mechanism. CONCLUSIONS: Healthcare professionals should
consider diltiazem-induced AIN in the differential diagnosis of a patient taking
diltiazem who develops acute renal failure.
PMID- 9640486
TI - Mibefradil: a new class of calcium-channel antagonists.
AB - OBJECTIVE: To describe the pharmacology, pharmacokinetics, and clinical efficacy
of mibefradil compared with other agents used for hypertension and angina. DATA
SOURCES: A MEDLINE search was performed for the period of January 1980 through
September 1997 using the key terms mibefradil or Ro 40-5967. All articles written
in English were considered for review. STUDY SELECTION AND DATA EXTRACTION: All
clinical studies involving mibefradil were evaluated. Preclinical data were
included if these data were not adequately represented in clinical (human)
studies. DATA SYNTHESIS: Mibefradil is the first member of a new class of calcium
channel antagonists (CCAs) that block the T-type calcium channels. A long
elimination half-life makes once-daily dosing feasible, and the drug's lack of
negative inotropy and reflex tachycardia distinguishes it from other available
CCAs. When administered at recommended dosages (50 or 100 mg once daily),
mibefradil reduces blood pressure over 24 hours in patients with hypertension,
improves exercise capacity, and relieves anginal symptoms in patients with
chronic stable angina pectoris. CONCLUSIONS: Clinical studies have found that the
antihypertensive effects of mibefradil are comparable with those of nifedipine,
verapamil, and amlodipine, and more effective than those of diltiazem. These
effects result from peripheral vasodilation and a slight reduction in heart rate.
Selective vasodilation of the coronary vasculature makes it an effective
antianginal agent when used alone or added to beta-blocker therapy. Mibefradil
demonstrates no significant effects on cardiac contractility, and no adrenergic
stimulation resulting in reflex tachycardia. Therefore, it may have some
advantages over currently available CCAs, especially in patients with congestive
heart failure, although such advantages are unproven in published clinical
trials. Ongoing clinical studies, including the Mortality Assessment in
Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to
clarify mibefradil's place in cardiovascular therapy.
PMID- 9640487
TI - Ranitidine bismuth citrate in the treatment of Helicobacter pylori infection and
duodenal ulcer.
AB - OBJECTIVE: To review the clinical pharmacology of ranitidine bismuth citrate in
the treatment of Helicobacter pylori (HP) infection and duodenal ulcer. DATA
SOURCES: A MEDLINE search of the English-language literature from 1992 to January
1997 was conducting using the key terms Tritec, ranitidine, and bismuth.
References of articles pertaining to treatment of duodenal ulcer or HP were
extensively searched for relevant sources. DATA EXTRACTION: All articles
pertaining to ranitidine bismuth citrate were considered for inclusion, with
emphasis placed on randomized, double-blind trials. Priority was placed on data
pertaining to regimens that are currently approved by the Food and Drug
Administration for the treatment of duodenal ulcer in conjunction with HP. DATA
SYNTHESIS: Each tablet of ranitidine bismuth citrate 400 mg contains 162 mg of
ranitidine base, 128 mg of trivalent bismuth, and 110 mg of citrate. It uses the
acid-suppressive actions of ranitidine and the antimicrobial and mucosal
protective effects of bismuth to eradicate HP. Ranitidine bismuth citrate in
conjunction with clarithromycin represents one of four treatment regimens
currently approved in the US for duodenal ulcer associated with HP infection. In
four double-blind, randomized trials, this agent has achieved HP eradication
rates of 73-94% and duodenal ulcer healing rates of 73-89%. It is given twice
daily for 28 days, and is associated with very low rates of adverse effects.
CONCLUSIONS: Relative to some therapeutic alternatives, ranitidine bismuth
citrate plus clarithromycin may be simpler to take and have less adverse effects,
but may be more expensive. Compared with omeprazole plus clarithromycin, it is
less expensive, may have lower ulcer healing rates, but may be more effective in
eradicating HP. The role of ranitidine bismuth citrate will continue to evolve as
more patients are treated, and other regimens continue to be tested for duodenal
ulcer healing and HP eradication.
PMID- 9640488
TI - Beyond benzodiazepines: alternative pharmacologic agents for the treatment of
insomnia.
AB - OBJECTIVE: To review the epidemiology, etiology, and classification of insomnia
and provide an overview of the pharmacologic therapy of insomnia. Novel
nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well
as nonprescription products such as valerian and melatonin, are reviewed in
detail. DATA SOURCES: A MEDLINE search was performed to identify relevant
clinical studies, case reports, abstracts, and review articles published between
April 1992 and December 1997. Key search terms included insomnia,
benzodiazepines, zolpidem, zopiclone, zaleplon, Cl 284,846, melatonin, and
valerian. Additional references were obtained from the lists of review articles
and textbooks. DATA EXTRACTION AND SYNTHESIS: Data concerning the safety and
efficacy of the hypnotic agents were extracted from all available clinical trials
and abstracts. Background information regarding insomnia, benzodiazepines, and
other hypnotics was extracted from the most current literature, including review
articles and textbooks. CONCLUSIONS: New developments in benzodiazepine receptor
pharmacology have introduced novel nonbenzodiazepine hypnotics that provide
comparable efficacy to benzodiazepines. Although they may possess theoretical
advantages over benzodiazepines based on their unique pharmacologic profiles,
they offer few, if any, significant advantages in terms of adverse effects. Over
the-counter agents such as valerian and melatonin may be useful in alleviating
mild, short-term insomnia, but further clinical trials are required to fully
evaluate their safety and efficacy.
PMID- 9640489
TI - Selective serotonin-reuptake inhibitor-induced movement disorders.
AB - OBJECTIVE: To compile and evaluate all available data suggesting an association
between selective serotonin-reuptake inhibitor (SSRI) administration and the
occurrence of movement disorders, and to characterize these reactions in terms of
onset, duration, treatment and outcome, and potential predisposing factors.
METHODOLOGY: Reports of movement disorders were identified by conducting a
comprehensive literature search that included tertiary adverse drug reaction
resources, MEDLINE, EmBASE, Biological Abstracts, Current Contents, Reactions,
ClinAlert, and International Pharmaceutical Abstracts. In addition, reports were
solicited from the Canadian proprietary manufacturers of SSRIs, and from the
Therapeutic Products Program of Health Canada. Each case was then classified
according to the description of the movement disorder, based on predefined
diagnostic criteria. RESULTS: A total of 127 published reports of SSRI-induced
movement disorders were identified involving akathisia (n = 30), dystonia (19),
dyskinesia (12), tardive dyskinesia (6), parkinsonism (25), and 15 cases of mixed
disorders. Ten isolated cases of bruxism were identified. Ten additional reports
could not be classified. Manufacturers of SSRIs provided 49 reports of akathisia,
44 of dystonia, 208 of dyskinesia, 76 of tardive dyskinesia, 516 of parkinsonism,
and 60 of bruxism. Treatment strategies included discontinuation of the SSRI;
dosage reduction; or the addition of a benzodiazepine, beta-blocker, or
anticholinergic agent. CONCLUSIONS: SSRI use appears to be associated with the
development of movement disorders, as either a direct result of the drug or
exacerbation of an underlying condition. Predisposing factors may include the use
of neuroleptics, existing neurologic diagnoses, or preexisting movement
disorders. Clinicians should be cognizant of the potential for these reactions,
as prompt recognition and management is essential in preventing potentially
significant patient morbidity.
PMID- 9640490
TI - Beta-blockers and depression: the more the murkier?
AB - OBJECTIVE: To review the literature regarding the purported association between
oral ingestion of beta-blocker drugs and depressed mood. DATA SOURCE: MEDLINE was
searched for published articles using the key words propranolol, atenolol,
metoprolol, nadolol, timolol, beta-blocker, beta-adrenergic antagonist, or beta
adrenergic blocker in combination with the key words depression, depressive
symptomatology, major depressive disorder, or depressed mood from January 1966
through December 1996. DATA SYNTHESIS: Findings regarding the association are
equivocal. Plausible explanations include study design, case definition, and
confounding disease states. Most of the evidence supporting an association has
used case series and case reports. Findings from cross-sectional observational
studies and case-control studies are equivocal. Case definition and measurement
instruments may partially explain these inconsistencies. Studies using a
diagnosis of depression generally do not support the relationship. Trials using
depressive symptoms are about evenly split, but they have generally enrolled a
small number of patients and have questionable statistical power. Studies
defining antidepressant prescriptions dispensed as a marker for depression
generally support the association. Evidence exists both for and against the
hypothesis that lipophilic beta-blockers cause more depression than do
hydrophilic beta-blockers. CONCLUSIONS: beta-Blockers may have been unjustly
associated with depression and their use avoided for that reason. Future studies
into the association between depression and beta-blocker use should evaluate
whether the association is affected by case definition and study design
characteristics, including disease, dose-response, bias, measurement error, or
ability to precisely measure the length of the exposure.
PMID- 9640491
TI - Oral ketoconazole in cutaneous fungal infections.
AB - Few data are available on the mechanism by which oral ketoconazole reaches the
stratum corneum and exhibits its antifungal activity. The rapid onset of effect
and the isolation of ketoconazole from the sweat support the theory that this
agent reaches its site of action through eccrine sweat secretion. However,
passive diffusion from the bloodstream and sebum secretion may also account for
the antimycotic effect at the level of the stratum corneum. Oral ketoconazole has
been shown to be effective in a variety of cutaneous fungal infections. However,
systemic antifungal therapy is best reserved for extensive infections or those
resistant to topical therapy.
PMID- 9640492
TI - Movement disturbances associated with the use of selective serotonin-reuptake
inhibitors.
PMID- 9640493
TI - Comment: modification of weight-based heparin nomogram.
PMID- 9640494
TI - Comment: cost-effective pharmaceutical care for HIV disease.
PMID- 9640495
TI - Expression of the autoreactive Ig repertoire in a large family, with high
prevalence of thyroid autoimmune diseases.
AB - We have investigated the autoreactive Ig repertoire expressed by sera Ig of
patients and healthy relatives individuals, who belong to a large family with
high prevalence of autoimmune thyroid diseases (AITD). We have used a panel of
thyroid, muscular and nuclear self antigens. IgG autoantibodies directed against
thyroid antigens were found in 17 out of 29 patients (58.62%) and in 10 out of 46
(21.7%) of relatives sera which suggested that some relatives were either
predisposed to develop the AITD or already affected with AITD. IgM natural
autoantibodies (NAAb) directed against muscular and nuclear antigens were found
in 27 out of 46 (58.69%) of healthy individuals but not exhibited in all of the
patients. In relative's sera, the presence of anti-Tg and anti-TPO seems to be
associated with the increase of the NAAb activity. Our Data suggested that The
emergence of anti-Tg and anti-TPO auto-antibodies is secondary to a polyclonal
activation.
PMID- 9640496
TI - [Myxomatosis in Tunisia: seroepidemiological study in the Monastir region
(Tunisia)].
AB - A sero-epidemiological study of myxomatosis, realized in the region of Monastir,
confirmed the existence and the prevalence of the disease in its nodular form.
Different strains of the myxomatosis virus were isolated and identified by gel
immunodiffusion test (GID) using specific polyclonal sera. Serological analyses
using complement fixation (FC) and (GID) tests allowed the detection of specific
antibodies in sera from both healthy and sick animals. The results also confirmed
the better sensitivity of the FC over the GID. Overall rates infection of herds
and animals were 54.9% and 32.63% (p < 0.05), respectively, as revealed by
serological testing. These rates increase with the size of herds. Geographic
distribution of myxomatosis cases suggests that the disease first appeared in the
coastal region then moved inside the Sabel area. Breeding and farming conditions,
associated with deficiency in sanitary and medical measures, are at the origin of
the introduction and the wide distribution of myxomatosis in this region.
PMID- 9640497
TI - [Isolation of salmonella in wastewaters and study of indicator bacteria survival
in soils].
AB - Detection of salmonella in wastewaters was done in semi-industrial pilot plant.
In parallel, survival of indicator bacteria (feacal coliforms and feacal
streptococci) in the soil was evaluated into a laboratory incubation device.
Results revealed the isolation of 21 strains of salmonella in 7 campaigns of
analysis on DCLS media, and 6 strains on lactose-green-brilliant and phenol red
media in 2 campaigns. Salmonella were recovered in all the lines of wastewater
treatment. The study led on the survival of coliforms and streptococci bacteria
allowed the conclusion that feacal streptococci introduced by wastewaters were
more qualified to survive in the soil than feacal coliforms. On the other hand,
feacal coliforms appeared more sensitive to the biological factors of the soil
than feacal streptococci. The ambient temperature of incubation situated between
12 and 24 degrees C seemed suitable for bacteria survival in the soils.
PMID- 9640498
TI - [Epidemiological and clinical profile of superficial mycoses in the Monastir
region (Tunisia). Retrospective study (1991-1994) of 3578 cases].
AB - Despite of socio-economical improvement in our population and the efficacy of
available antifungal treatment, superficial mycoses remain a common condition in
dermatologic practice. To determine the epidemio-clinical pattern of superficial
mycoses in our region, a retrospective study of 3578 cases have been carried out
in the Department of Dermatology of the University Hospital of Monastir during a
4 year-period. The mean age of patients was 33 years (range: 6 months-91 years).
The male to female sex-ratio was 0.82. Rural origin, history of previous mycoses,
diabetes, topic or systemic corticosteroids and the presence of animals in
surroundings were the most predisposing factors. The most frequent clinical
patterns were: tinea corcoris and pedis (40.3%), Tinea versicolor (21.6%), Tinea
capitis (9.7%) dermatophytosis of hairless skin (9.6%) and onychomycosis (8.6%).
Dermatophyte was the most frequent (55.5%). The occurrence of superficial mycose
especially if it affects diffuse area of the body, or if it is relapsing and
resistant to treatment, requires looking for predisposing factors.
PMID- 9640499
TI - [Study of symbiotic, serological and antibiotic resistance characteristics of
different Rhizobium cicerii strains].
AB - The symbiotic performance of 24 isolates of Rhizobium Cicerii, collected from
different Tunisien soils, were studied in a growth room and compared to the
performance of two international strains (Som and 43). The antibiotic and
serologic tests showed a large biogenetic diversity among the different isolates.
Three serogroups gathering 18 isolates have been identified. Monchar strain
(isolat 12) was shown to be resistant to all the six different antibiotic used.
The standard strain 43 produced the greatest number of nodules and the best
nitrogen yield in association with "Amdoun" roots, whereas the Menzel bouzelfa
isolate brought about the best nitrogen yield in association with "Amdoun" and
thus was the most efficient. An interesting result, consisted on the existence of
a significant correlation (r = 0.67) between streptomycin resistance of the
isolates and their capacity of nodule initiation (infectivity).
PMID- 9640500
TI - [Pollen density calender in Tunisia].
AB - The pollen calendar of the region on Tunis atmosphere was established and the
weekly variations of the pollen density of the 25 main taxones were studied. This
calendar showed an identity reflecting the surrounding vegetation modulated by
the pollen production of neighbouring regions and other far-off areas. This
should allow the allergist to predict the critical periods for the patients and
to advice him the specific treatment. On the other hand, it would demonstrate the
usefulness, in using a series of skin tests, certain European pollens which are
partially or totally absent in the atmosphere of Tunis. However, it would be
desirable controlling the allergic capacity of pollens which are not tested up to
now and could be found in non negligible concentrations in the atmosphere.
PMID- 9640501
TI - [Estimation of fertility and quality of oocytes emitted by the clam Ruditapes
decussatus (Linnaeus 1758) during experimental inductions].
AB - Experimental inductions were carried out on some genitors of clams Ruditapes
decussatus to obtain sexual emissions and estimate the fecondity of this species.
The genitors were collected from two sites of tunisian littoral. Higher percent
of oocytes was found in summer with a maximum of 52 x 10(4) oocytes in Gargour
(Golf of Gabes) against 45 x 10(4) in Menzel-Jemil (Lagoon of Bizerte). The
observation under the electronic microscope of free oocytes allowed us to
subdivised them in three groupes: immatures, matures and atretics. Only mature
oocytes were susceptible to be feconded and underwent larval development with
unknown proportion.
PMID- 9640502
TI - [Cerbussowia cerruti Wilhelmi 1901, from the Tunisian Golf (Platyhelminths,
marine Tricladida)].
AB - Cerbussowia cerruti Wilhelmi, 1909 (Plathyhelminthe, Turbellaria, Tricladida) is
described in Tunisia for the first time. A morphological, anatomical and
histological accounts of this marine flatworm are presented. Some differences
between the anterior ends of the tunisian animals and accounts in the literature
are discussed.
PMID- 9640503
TI - [Trace metals: zinc and copper in Tunisian littoral fishes].
AB - Investigations have been carried out in order to find out whether zinc and copper
are or not accumulated in flesh and organs of some edible fish of a polluted
area, namely Sfax. Tracking zinc and copper was our first aim, the second was the
determination of an organotropism of the two metals. Finally, our results, would
help stating whether or not Sfax-shore is polluted with zinc and copper.
PMID- 9640504
TI - [Minerals in Tunisia's drinking water].
AB - We have made the physico-chemical analysis of drinking waters sampled from
different Tunisian areas. The results obtained show that those waters are rich in
mineral elements particularly those of the south of the country. Calcium and
magnesium level in south drinking water is about three times higher than the
maximum admitted concentration by WHO an EEC. The sodium, chloride and sulfate
level is twice higher. The nitrate contents slightly exceeds the EEC guide level.
The high mineralization observed needs a chemical quality improvement of those
waters.
PMID- 9640505
TI - Hormone replacement.
PMID- 9640506
TI - Patients as partners. Encouraging lifestyle changes through feedback.
PMID- 9640507
TI - Close friends as patients in rural practice.
PMID- 9640508
TI - Medical services supply measurement. A case for access modeling.
PMID- 9640509
TI - No remuneration for telephone renewals.
PMID- 9640510
TI - Rejecting the facts.
PMID- 9640511
TI - Keeping an open mind.
PMID- 9640512
TI - What we need to know.
PMID- 9640513
TI - Preparing LET solution.
PMID- 9640514
TI - Comparing antihypertensive agents.
PMID- 9640515
TI - Therapeutic approach to hypertension during pregnancy.
AB - QuestionQuite a few of my pregnant patients have hypertensive disorders. What is
the threshold for treating hypertension during pregnancy? Which of the various
antihypertensive agents are considered safe during pregnancy?AnswerPharmacologic
therapy could benefit mother and baby when diastolic pressure exceeds 110 mm Hg.
Preeclampsia must be followed closely. Methyldopa (eg, Aldomet) and hydralazine
(eg, Apresoline) are still the drugs of choice during pregnancy, although the
safety and efficacy of calcium channel blockers and Beta-blockers appear well
established.
PMID- 9640516
TI - Ophthaproblem. Chalazion.
PMID- 9640517
TI - Dermacase. Tuberous sclerosis (Bourneville's disease).
PMID- 9640518
TI - Emergency treatment of paraphimosis.
PMID- 9640519
TI - Should we be giving all children with otitis media antibiotics?
PMID- 9640520
TI - Peak flow meters for asthma patients. Do they up the benefits or up the costs?
PMID- 9640521
TI - Alternative treatments for menopausal symptoms. Qualitative study of women's
experiences.
AB - OBJECTIVE: To describe women's experiences with alternative treatments for
symptoms attributed to menopause. DESIGN: Descriptive qualitative study. SETTING:
Personal interviews and focus groups were conducted in private rooms at the
Toronto Hospital; telephone interviews were conducted at mutually convenient
times. PARTICIPANTS: Thirteen perimenopausal women with a mean age of 52.6 +/-
2.6 years who were experiencing symptoms attributed to menopause and were using
alternative therapies participated in the study. METHOD: Women using alternative
therapies for menopausal symptoms were recruited via posted notices and were
screened over the telephone. Data were collected during semistructured personal
interviews, telephone interviews, and a focus group. All interviews were
audiotaped, transcribed, and mailed to participants for verification. Recruitment
continued until theme saturation was reached. MAIN FINDINGS: Because of their
"natural" origin, the women perceived alternative treatments to be safe and
considered them somewhat effective. Factors influencing use of alternative
therapies included personal control over health, confidence in advice from
nonphysicians, perceived pressure from physicians to use hormone replacement
therapy, and physicians' disinterest and frequently negative attitudes toward
alternatives. CONCLUSION: Personal control was a central issue. Helping women
during their menopausal years feel they have some control over their health,
including their informed choice of treatments, might help them to trust their
physicians more and to feel more confident in their ultimate treatment decisions,
which might include improvements in health behaviour.
PMID- 9640522
TI - [Factors influencing the adoption of hormone replacement therapy].
AB - OBJECTIVE: To develop and test the metrologic qualities of a questionnaire for a
survey on determining factors in initiating hormone replacement therapy (HRT),
using Ajzen's planned behaviour theory. DESIGN: Semistructured interviews to
collect the behavioural beliefs needed to develop the questionnaire and the test
retest. SETTING: Family medicine practices and the community. PARTICIPANTS: In
two family medicine practices, 42 women completed semistructured interviews that
yielded the beliefs needed to design the questionnaire for the core survey.
Thirty other women from the community took part in the test-retest 2 weeks later.
MAIN OUTCOME MEASURES: The internal consistency of the constructs (tendency of
answers within a group of questions) was determined using Cronbach's alpha
coefficient. Stability of the global constructs (proportion of subjects who had
an absolute difference in their scores of less than 1 between the two
measurements) was determined using the adjusted agreement coefficient (adjusted
Po). RESULTS: Findings for 12 of the 14 global constructs were above the
acceptance threshold of 0.60. In one case alpha could not be measured because
there was only one question for measuring it. On the test-retest, 12 of the 14
adjusted Pos had a reliability rating at or above 80%. CONCLUSION: The
questionnaire developed using Ajzen's planned behaviour theory had the requisite
metrologic qualities for integration into the core survey on determining factors
for initiating HRT.
PMID- 9640523
TI - Hypercholesterolemia screening. Does knowledge of blood cholesterol level affect
dietary fat intake?
AB - OBJECTIVE: To assess whether knowing blood cholesterol test results influences
people's intention to lower their dietary fat intake and to assess changes in
diet after 3 months. DESIGN: Randomized clinical study. SETTING: Two hospital
based family medicine centres. PARTICIPANTS: A total of 526 patients aged 18 to
65, without prior knowledge of their blood cholesterol levels, were recruited.
Seventy did not appear for their appointments, and 37 did not meet study
criteria, leaving 419 participants. From that group, 391 completed the study.
INTERVENTIONS: Patients submitted to cholesterol screening were randomly assigned
to one of two groups, completing the study questionnaires either before (control
group) or after (experimental group) being informed of their screening test
results. All participants were called 3 months after transmission of test results
to assess their dietary fat intake at that time. MAIN OUTCOME MEASURES:
Differences in intention to adopt a low-fat diet reported between the
experimental and control groups and differences in dietary fat intake
modification after 3 months between patients with normal and abnormal blood
cholesterol test results. RESULTS: Knowledge of test results influenced patients'
intentions to adopt low-fat diets (F1,417 = 5.4, P = .02). Patients reported
lower mean dietary fat intake after 3 months than at baseline (P < .0001). The
reduction was greater in patients with abnormal screening results (F2,388 = 3.6,
P = .03). CONCLUSIONS: Being informed of personal blood cholesterol levels
effects an immediate change in eating habits that translates into reduced dietary
fat intake.
PMID- 9640525
TI - Initial experience of McMaster SmokeStop. Smoking Cessation Clinic at McMaster
Family Practice Unit.
AB - PROBLEM ADDRESSED: There are very few smoking cessation resources in the
community, and many family physicians have not incorporated smoking cessation
counseling into their practices. Yet many smokers are interested in individual
assistance to stop smoking. McMaster SmokeStop is a unique smoking cessation
program that operates within the Family Practice Unit at McMaster University
Medical Centre. The program has been in operation since October 1994. Additional
clinics have been established at three other Hamilton hospitals and a community
health centre in the past year. OBJECTIVE OF PROGRAM: To assist people to change
smoking behaviour by quitting, cutting down, or making progress toward quitting
as manifested by an advance in stage of change using the Prochaska and DiClemente
model. The program was established in response to requests from various health
care providers who wanted to refer difficult and challenging smoking patients.
MAIN COMPONENTS OF PROGRAM: Using an individual counseling approach, the program
assists smokers with the use of reflective listening and support as well as, when
indicated, acupuncture, nicotine patch, nicotine gum, stress management, and
behaviour modification. Thirty to 60 minutes are allowed for initial appointments
and 15 to 30 minutes for follow-up appointments. CONCLUSION: The program has
become a popular resource for health care providers in the community who refer
difficult smoking patients. Because of increasing numbers of smokers who wish to
attend, the clinics have expanded considerably.
PMID- 9640524
TI - Alternative treatments for menopausal symptoms. Systematic review of scientific
and lay literature.
AB - OBJECTIVE: To review the scientific literature on common alternative remedies for
treatment of symptoms attributed to menopause and to contrast this with available
lay literature. QUALITY OF EVIDENCE: Scientific articles were identified by
searching MEDLINE, CINAHL, and HEALTH databases from 1966 to mid-1997 for English
language articles. More than 200 references were reviewed; 85 were selected for
citation based on specific reference to alternative medicine for symptoms
commonly attributed to menopause (e.g., hot flashes), to the effects of changing
estrogen levels (e.g., irregular menses, vaginal dryness), and to reported side
effects of the treatments. MAIN FINDINGS: The scientific literature was
categorized under the headings nutritional supplements, herbal remedies,
homeopathic remedies, and physical approaches. Some scientific evidence of the
safety and efficacy of alternative treatments during menopause was uncovered,
with the strongest evidence emerging in favour of phytoestrogens, which occur in
high concentrations as isoflavones in soy products. CONCLUSIONS: In available
controlled studies, the strongest data support phytoestrogens for their role in
diminishing menopausal symptoms related to estrogen deficiency and for possible
protective effects on bones and the cardiovascular system. Randomized controlled
trials, standardization of dosage, and accurate safety and efficacy labeling are
required to ensure proper use of alternative remedies.
PMID- 9640526
TI - Eradicating tuberculosis. Report on the National Consensus Conference on
Tuberculosis.
PMID- 9640527
TI - BC whiplash initiative.
PMID- 9640528
TI - Nucleus and gene expression.
PMID- 9640529
TI - New systems for replicating DNA in vitro.
AB - Current paradigms for the regulation of genomic DNA replication in eukaryotes are
derived primarily from cell fusion experiments, yeast genetics, and from in vitro
assays in Xenopus egg extracts. Initially, many aspects seemed irreconcilably
different among the various organisms and model systems. In the past year,
however, divergent approaches have arrived at a consensus on how the cell cycle
regulates the initiation of DNA replication. All major players appear to be
conserved from yeast to vertebrates, yet the important challenge of
reconstituting eukaryotic replication from purified components remains. Three
novel in vitro assays that replicate nuclear templates bring us closer to this
goal.
PMID- 9640530
TI - DNA mismatch repair and cancer.
AB - Mutations in DNA mismatch repair (MMR) genes have been associated with hereditary
nonpolyposis colorectal cancer. Studies in bacteria, yeast and mammals suggest
that the basic components of the MMR system are evolutionarily conserved, but
studies in eukaryotes also imply novel functions for MMR proteins. Recent results
suggest that mutations in MMR genes lead to tumorigenesis in mice, but DNA
replication errors appear to be insufficient to initiate intestinal tumorigenesis
in this model system. Additionally, MMR-deficient cell lines display a mutator
phenotype and resistance to several cytotoxic agents, including compounds widely
used in cancer chemotherapy.
PMID- 9640531
TI - SMC protein complexes and higher-order chromosome dynamics.
AB - The structural maintenance of chromosome (SMC) family of proteins represents an
expanding group of chromosomal ATPases that are highly conserved among Bacteria,
Archaea and Eukarya. During the past year, significant progress has been made
towards understanding the cellular functions and molecular activities of this new
class of proteins. Emerging evidence suggests that eukaryotic SMC proteins form
large protein complexes with non-SMC subunits and act as key components for a
wide variety of higher-order chromosome dynamics.
PMID- 9640532
TI - The cellular organization of gene expression.
AB - Recent cell biological observations have provided new insights into how
transcription, pre-mRNA splicing and 3' processing are organized and coordinated
with each other in the mammalian cell nucleus. Morphological observations are
supported by biochemical evidence that suggests physical interactions between
components of the transcription and RNA processing machineries. A working model
of the cellular organization of gene expression is now emerging.
PMID- 9640533
TI - Telomeres, the nucleolus and aging.
AB - Reactivation of telomerase in cultured human cells extends their replicative life
span beyond the Hayflick limit. How telomere shortening triggers cell senescence
and whether it contributes to aging in vivo are under investigation. Studies in
yeast have revealed another site critical to cellular aging: the nucleolus. The
accumulation of ribosomal DNA circles is a cause of aging in this organism. The
possible relevance of this mechanism to human aging is also being considered.
PMID- 9640534
TI - Life with nucleosomes: chromatin remodelling in gene regulation.
AB - In the past year, the role of chromatin has emerged at the forefront of
transcription research. Discovery and characterisation of the chromatin modifying
machinery have significantly advanced our understanding of the molecular
activities that establish a transcriptionally competent substrate in vivo, and
have underscored the importance of the part played by chromatin in the regulation
of transcription.
PMID- 9640535
TI - Chromatin-remodeling factors: machines that regulate?
AB - Chromatin has shifted into the focus of attention as a key to understanding the
regulation of nuclear processes such as transcription. Protein machines have been
described that use the energy of ATP to render chromatin dynamic and hence
active, but which may also be involved in chromatin assembly. The discovery of
three different Drosophila nucleosome remodeling complexes that contain imitation
switch (ISWI), an ATPase with a high degree of sequence conservation from yeast
to human, points to a central function of this ATPase in chromatin dynamics.
PMID- 9640536
TI - Chromo-domain proteins: linking chromatin structure to epigenetic regulation.
AB - Chromo-domain proteins appear to be a central component in the epigenetic
regulation of heterochromatin function and euchromatic gene expression. The
recent discovery of a variety of interacting partners of chromo-domain proteins
is yielding new molecular insights into epigenetic regulatory processes acting at
the level of higher order chromatin structure.
PMID- 9640537
TI - Locus control regions, chromatin activation and transcription.
AB - The past year has seen interesting advances in our understanding of the action of
locus control regions. For the first time, the chromosomal distance was described
in detail as a parameter in positive/negative regulation of transcription via
gene competition. A number of publications have also described negative
regulatory elements which restrict the action of locus control regions and other
regulatory regions to specific genes and/or specific tissues. The emerging
picture indicates that several very different types of negative regulation ensure
that transcriptional activation occurs only in the appropriate cells.
PMID- 9640538
TI - TCF: transcriptional activator or repressor?
AB - T cell factor, or TCF, has been identified as the transcriptional response factor
activated by Wnt-1 and Wingless signalling. TCF is thought to be a potent
architectural factor which facilitates assembly of multiprotein enhancer
complexes. Its deregulation in the colonic epithelium, and in other cells, leads
to cancer. This raises the question of how TCF is kept inactive in unstimulated
cells.
PMID- 9640539
TI - Co-activators and co-repressors in the integration of transcriptional responses.
AB - The nuclear hormone receptors are DNA binding transcription factors that are
regulated by binding of ligands, switching them from an inactive or repressive
state to gene-activating functions. Recent evidence supports the hypothesis that
many nuclear receptors switch, in a ligand-dependent manner, between binding of a
multicomponent co-repressor complex containing histone deacetyltransferase
activity, and binding of a co-activator complex containing factors with histone
acetyltransferase activity that are further regulated by diverse signal
transduction pathways. The identification of these limiting co-repressor and co
activator complexes and their specific interaction motifs, in concert with
solution of the structures of the receptor ligand-binding domain in apo (empty)
and ligand bound forms, indicates a common molecular mechanism by which these
factors activate and repress gene transcription.
PMID- 9640540
TI - The nuclear receptor ligand-binding domain: structure and function.
AB - In the past few years our understanding of nuclear receptor action has
dramatically improved as a result of the elucidation of the crystal structures of
the empty (apo) ligand-binding domains of the nuclear receptor and of complexes
formed by the nuclear receptor's ligand-binding domain bound to agonists and
antagonists. Furthermore, the concomitant identification and functional analysis
of co-regulators (transcriptional intermediary factors [TIFs], comprising co
activators and co-repressors) previously predicted from squelching studies, have
deepened this understanding. Recent data have provided the structural basis for
the specific recognition of ligands and the molecular mechanisms of agonism and
antagonism, enabling us to gain a comprehensive view of the early steps of
nuclear receptor action.
PMID- 9640541
TI - Transport routes through the nuclear pore complex.
AB - The nuclear pore complex can be considered to be the stationary phase of
bidirectional traffic between the nucleus and the cytoplasm. The mobile phase
consists of karyopherins, transport substrates, and the small GTPase Ran and its
modulators. Recently, the family of karyopherins was expanded with the
recognition of numerous open reading frames with limited homology to karyopherin
beta 1. In several cases, the specific substrates transported by the new
karyopherins have been identified, allowing the characterization of new pathways
into and out of the nucleus. However, the mechanisms of transport, particularly
the role of Ran, remain poorly understood.
PMID- 9640542
TI - Functions of the GTPase Ran in RNA export from the nucleus.
AB - Significant and exciting advances in the field of RNA and protein export have
been made recently, due in large part to discovery of the roles played by Ran, a
small, soluble GTPase present in both the nucleus and cytoplasm of all eukaryotic
cells. Ran is thought to be primarily bound to GTP in the nucleus and to GDP in
the cytoplasm, as a result of the assymetric distribution of factors that
interact with Ran to promote guanine nucleotide exchange (in the nucleus) and GTP
hydrolysis (in the cytoplasm). A key function of the nuclear Ran.GTP is to
support formation of complexes containing an export receptor (an exportin) and
cargos such as RNAs, RNPs or proteins that are destined for export. In the
cytoplasm, removal of the Ran.GTP from the complex results in its destabilization
and release of the export cargo. Although Ran.GTP is required for formation of
the export complex, GTP hydrolysis does not appear to be necessary for
translocation through the nuclear pore complex or cytoplasmic release.
Nevertheless, the GTPase of Ran does appear to be required in as yet unidentified
intranuclear steps prior to export of some, but not all, RNAs.
PMID- 9640543
TI - Nuclear envelope and nuclear pore assembly: analysis of assembly intermediates by
electron microscopy.
AB - At mitosis, the nucleus of higher eukaryotic cells disassemblies into components
which subsequently reform functional nuclear envelopes in the two daughter cells.
The molecular mechanisms underlying this remarkable morphological reorganization
are the focus of active investigation. Recent electron microscopy techniques have
provided intriguing glimpses of intermediate structures in both nuclear envelope
and nuclear pore complex reassembly.
PMID- 9640544
TI - Peripheral vascular disease, Part 2.
PMID- 9640545
TI - Money-irritation.
PMID- 9640546
TI - The safety of bleaching creams containing hydroquinone.
PMID- 9640547
TI - Hereditary papulotranslucent acrokeratoderma.
PMID- 9640548
TI - A dermatologic diary. Portrait of a new life.
PMID- 9640549
TI - Surgical management of rhinophyma.
PMID- 9640550
TI - Aquatic adversaries: shark bites.
PMID- 9640551
TI - Do you anticipate that you will be seeing a greater or lesser amount of patients
with melanoma due to the media blitz concerning sun awareness and skin
protection?
PMID- 9640553
TI - Rosaceous lymphedema: a rare variant of a common disorder.
AB - Rosaceous lymphedema is considered to be a rare and disfiguring variant of acne
rosacea. Cases remain difficult to treat and can challenge afflicted patients
both cosmetically and psychologically. We describe an unusual presentation of
rosaceous lymphedema and review the differential diagnosis of persistent facial
edema.
PMID- 9640554
TI - POEMS syndrome in a patient with diabetic ketoacidosis: case report and review.
AB - POEMS syndrome is an uncommon multisystem disorder characterized by the
combination of polyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changes. A 57-year-old man diagnosed with POEMS syndrome
after presenting with diabetic ketoacidosis and characteristic skin lesions is
reported. The dermatologic and systemic manifestations of this unusual syndrome
are reviewed.
PMID- 9640555
TI - Perceived deprivation of social touch in psoriasis is associated with greater
psychologic morbidity: an index of the stigma experience in dermatologic
disorders.
AB - Touch is a powerful medium of social validation. Patients with skin disorders
often experience social rejection when people avoid touching them, possibly
fearing contagion or filth. We examined the psychologic impact of the stigma
experience among 137 patients with moderate to severe psoriasis; 26.3 percent of
patients reported that during the previous month they had experienced an episode
when "people made a conscious effort not to touch them" because of their
psoriasis. The stigmatized group did not have greater psoriasis severity than the
non-stigmatized control group. However, in contrast to the non-stigmatized group,
the stigmatized group had higher (P = 0.0003) depression scores (in the range for
clinical depression, as measured by the Carroll Rating Scale for Depression), by
stepwise logistic regression analysis using a wide range of psychopathologic
measures as the independent variables. These findings underline the profound
impact of the stigma experience in psoriasis, and possibly other dermatologic
conditions that are associated with social stigma.
PMID- 9640556
TI - Effective sunscreen ingredients and cutaneous irritation in patients with
rosacea.
AB - Patients with rosacea are particularly susceptible to the irritation caused by
sunscreen ingredients. The purpose of this bilateral comparison study was to
examine the effects of different ingredients found in sunscreen on facial
cutaneous irritancy in patients with rosacea. patients clinically diagnosed with
rosacea were asked to test different preparations of common sunscreens on their
faces. The results show that the presence or absence of appropriate protective
ingredients, such as dimethicone and cyclomethicone in the vehicle, may prevent
irritation from other sunscreen ingredients in patients with inflammatory
conditions such as rosacea.
PMID- 9640557
TI - An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the
cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic
hyperkeratosis, and ichthyosis.
AB - A number of genetic, intrinsic, and extrinsic factors can cause conditions of
problem dry skin, marked by unusual dryness, rough texture, and extreme flaking
and scaling, that are generally not controlled by conventional moisturizers. A
study was undertaken to evaluate the safety and efficacy of two novel alpha
hydroxy acid (AHA)-containing creams in reducing the appearance and symptoms of
problem dry skin on subjects with a range of dry skin conditions, including
xerosis, epidermolytic hyperkeratosis, and ichthyosis. Twenty subjects completed
a course of treatment with either regular or extra strength AHA-blend cream on a
test site, compared with a currently marketed, non-AHA moisturizing lotion on a
control site. Subjects were treated for 4 weeks, with clinical evaluations
performed at weeks 0, 2, and 4. The test for mulations reduced symptoms and
improved cosmetic appearance following 2 weeks of use, with continued improvement
following 4 weeks of use. Improvements were significant compared to baseline and
compared to sites treated with the control lotion. Some patients experienced mild
to moderate local adverse effects; all subjects were able to continue using the
test product for the duration of the study.
PMID- 9640558
TI - The causes and treatment of pseudofolliculitis barbae.
AB - Pseudofolliculitis barbae, commonly referred to as "razor bumps" or "ingrown
hairs," is a papular and pustular, foreign body inflammatory reaction that can
affect any individual who has curly hair and who shaves. This condition is a
particular nuisance to African-Americans. This report will discuss the causes of
pseudofolliculitis barbae and present a systematic approach to treatment.
PMID- 9640559
TI - Chaos game representation of proteins.
AB - The present report proposes a new method for the chaos game representation (CGR)
of different families of proteins. Using concatenated amino acid sequences of
proteins belonging to a particular family and a 12-sided regular polygon, each
vertex of which represents a group of amino acid residues leading to conservative
substitutions, the method can generate the CGR of the family and allows pictorial
representation of the pattern characterizing the family. An estimation of the
percentages of points plotted in different segments of the CGR (grid points)
allows quantification of the nonrandomness of the CGR patterns generated. The
CGRs of different protein families exhibited distinct visually identifiable
patterns. This implies that different functional classes of proteins follow
specific statistical biases in the distribution of different mono-, di-, tri-, or
higher order peptides along their primary sequences. The potential of grid counts
as the discriminative and diagnostic signature of a family of proteins is
discussed.
PMID- 9640560
TI - Comparative molecular modeling study of the three-dimensional structures of
prostaglandin endoperoxide H2 synthase 1 and 2 (COX-1 and COX-2).
AB - To understand the structural features that dictate the selectivity of diverse
nonsteroidal antiinflammatory drugs for the two isoforms of the human
prostaglandin H2 synthase (PGHS), the three-dimensional (3D) structure of human
COX-2 was assessed by means of sequence homology modeling. The ovine COX-1
structure, solved by X-ray diffraction methods and sharing a 61% sequence
identity with human COX-2, was used as template. Both structures were energy
minimized using the AMBER 4.0 force field with a dielectric constant of 4r. (S)
Flurbiprofen, a nonselective COX inhibitor, and SC-558, a COX-2-selective ligand,
were docked at the cyclooxygenase binding site in both isozymes, evidencing the
role of different residues in the ligand-protein interaction. The 3D structures
of the constructed four ligand-enzyme complexes were refined by energy
minimization. Molecular dynamics simulations were also carried out, to understand
more deeply the structural origins of the selectivity. Distances calculated
during the dynamics process between the different ligands and the interacting
residues of the two PGHS isozymes provided evidence of the flexible nature of the
cyclooxygenase active site, permitting the identification of different conserved
and nonconserved residues as responsible for ligand selectivity.
PMID- 9640561
TI - Visualization of solvation structures in liquid mixtures.
AB - Spatial distribution functions of atomic densities. SDFs, have been proposed as a
natural starting point for analysis of local molecular structure in liquids and
solutions. The local structure in these systems is often complex and this is
reflected in the fact that SDFs can be difficult to visualize. Among the
different methods that can be used to visualize SDFs we discuss 3D isodensity
surfaces, cross-sections, and 'comic book' animations. We also discuss the
possibility of a simultaneous visualization of SDFs and other 3D fields, such as
the electron density. These techniques are all intended to emphasize and bring
out aspects of SDFs that promote a further understanding of the local molecular
structure. OpenGL-based software has been used under X-Windows to implement these
techniques, and we argue that high-quality molecular graphics need not be
expensive. Data from a molecular dynamics simulation of an equimolar binary
mixture of water and acetonitrile have been used to illustrate the discussion.
PMID- 9640562
TI - Modeling of the three-dimensional structure of the human melanocortin 1 receptor,
using an automated method and docking of a rigid cyclic melanocyte-stimulating
hormone core peptide.
AB - A model is presented of the melanocortin 1 receptor (MC1R), constructed by use of
an unbiased, objective method. The model is created directly from data derived
from multiple sequence analysis, a low-resolution EM-projection map of rhodopsin,
and the approximate membrane thickness. The model agrees well with available data
concerning natural mutations of MC1Rs occurring in different species. A model is
also presented of the most rigid ligand for this receptor, the cyclic
pentapeptide cHFRWG, shown docked in the receptor model. The receptor-ligand
complex model agrees well with available experimental data. The ligand is located
between transmembrane region 1 (TM1), TM2, TM3, TM6, and TM7 of the receptor.
Multiple interactions occur between ligand and receptor, including interactions
with Leu-48 (TM1), Ser-52 (TM1), Glu-55 (TM1), Asn-91 (TM2), Glu-94 (TM2), Thr-95
(TM2) Ile-98 (TM2), Asp-121 (TM3), Thr-124 (TM3), Phe-257 (TM6), Phe-283 (TM7),
Asn-290 (TM7), and Asp-294 (TM7) of the receptor.
PMID- 9640563
TI - External and internal electrostatic potentials of cholinesterase models.
AB - The electrostatic potentials for the three-dimensional structures of
cholinesterases from various species were calculated, using the Delphi algorithm,
on the basis of the Poisson-Boltzmann equation. We used structures for Torpedo
californica and mouse acetylcholinesterase, and built homology models of the
human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and
human butyrylcholinesterase. All these structures reveal a negative external
surface potential, in the area around the entrance to the active-site gorge, that
becomes more negative as the rim of the gorge is approached. Moreover, in all
cases, the potential becomes increasingly more negative along the central axis
running down the gorge, and is largest at the base of the gorge, near the active
site. Ten key acidic residues conserved in the sequence alignments of AChE from
various species, both in the surface area near the entrance of the active-site
gorge and at its base, appear to be primarily responsible for these potentials.
The potentials are highly correlated among the structures examined, down to
sequence identities as low as 35%. This indicates that they are a conserved
property of the cholinesterase family, could serve to attract the positively
charged substrate into and down the gorge to the active site, and may play other
roles important for cholinesterase function.
PMID- 9640564
TI - Transcanalicular laser-assisted revision of failed dacryocystorhinostomy.
AB - BACKGROUND AND OBJECTIVE: Despite the high success rate of external
dacryocystorhinostomy (DCR), recurrent tearing after DCR can be troublesome. The
authors performed transcanalicular revision in 6 patients with failed DCR.
PATIENTS AND METHODS: With the use of a continuous wave Nd:YAG laser with a
sclerostomy probe, the internal ostium was reopened by a transcanalicular
approach. The authors applied 0.4 mg/ml of mitomycin-C around the opening for 5
minutes intranasally and inserted a silicone tube as a stent. RESULTS: A total of
7 operations were performed in 6 patients. The operation was successful after the
first revision in 5 of the 6 patients, but 1 of the patients required a second
procedure. CONCLUSIONS: The transcanalicular laser-assisted revision has several
advantages. It is simple and fast, skin incision is avoided, there is good
hemostasis, it is less traumatic, and there is less postoperative morbidity.
PMID- 9640565
TI - Combined intraocular and strabismus surgery.
AB - BACKGROUND AND OBJECTIVE: To study the results of combined intraocular and
strabismus surgery. PATIENTS AND METHODS: Combined surgery was done in 14
patients. In 10 of these patients, cataract and strabismus surgery were combined.
One had a penetrating keratoplasty, and another required placement of a glaucoma
valve implant. In one patient trabeculectomy, pupilloplasty, and lensectomy were
done, and one patient needed repair of a leaking bleb. RESULTS: The strabismus of
most patients was significantly improved. Eleven patients (79%) were orthophoric
+/- 10 prism diopters (PD). Visual outcome was good in patients with no
structural abnormalities who were compliant with occlusion therapy, if
applicable. CONCLUSIONS: Combined intraocular and strabismus surgery has a
success rate comparable with that of standard strabismus surgery.
PMID- 9640566
TI - Comparison of pain, motility, and preoperative sedation in cataract
phacoemulsification patients receiving peribulbar or sub-Tenon's anesthesia.
AB - BACKGROUND AND OBJECTIVES: The authors hoped to reduce the need for preoperative
sedation and intravenous pain medication during cataract surgery by converting
from peribulbar anesthesia to sub-Tenon's anesthesia. PATIENTS AND METHODS: A
consecutive series of 2453 cataract patients' charts were reviewed. Each patient
had previously watched a videotape explaining the anesthetic method to be used.
Requests for preoperative sedation were compared between patients who received
peribulbar or sub-Tenon's anesthesia. A sample of 200 charts of nonsedated
patients were reviewed to compare intraoperative pain and motility. RESULTS:
Intraoperative freedom from pain was reported by 91% of the peribulbar patients
and 99% of the sub-Tenon's patients. Preoperative sedation was reduced from 26%
of the peribulbar patients to 6.7% of the sub-Tenon's patients. CONCLUSIONS: Sub
Tenon's anesthesia provided excellent intraoperative pain relief and reduced the
need for preoperative sedation, making it a satisfactory anesthetic technique for
patients undergoing cataract phacoemulsification in an ambulatory surgery
facility.
PMID- 9640567
TI - Intraocular pressure in nonglaucomatous eyes with pseudoexfoliation syndrome
after cataract surgery.
AB - BACKGROUND AND OBJECTIVE: To investigate the course of the intraocular pressure
(IOP) in nonglaucomatous patients with pseudoexfoliation (PSX) syndrome after
cataract surgery. PATIENTS AND METHODS: In a prospective age-matched controlled
clinical study, 23 consecutive patients with PSX were studied and compared with a
control group of 23 patients. The IOP was measured by applanation tonometry
preoperatively, and postoperatively on day 1, after 4 weeks, and after 6 months.
All patients were operated on with a self-sealing 7-mm scleral tunnel incision,
phacoemulsification, and posterior chamber intraocular lens (IOL) implantation.
RESULTS: Preoperatively the IOP was similar between both groups (P = .962). At
the first postoperative day the IOP was below 22 mm Hg in all cases. After 4
weeks and 6 months a mean decrease of 3.88 mm Hg (P = .001) in the control group
and of 3.15 mm Hg (P = .002) in the PSX group was observed; this difference was
not statistically significant (P = .543). CONCLUSIONS: At 1 day postoperatively
no pressure increase was observed in the eyes with PSX after scleral tunnel
incision and phacoemulsification. Six months after cataract extraction with IOL
implantation, the tension level decreased in the presence of PSX similarly as in
normal eyes.
PMID- 9640568
TI - The effect of 1% apraclonidine on intraocular pressure after cataract surgery.
AB - BACKGROUND AND OBJECTIVE: To measure the effect of 1% apraclonidine hydrochloride
eyedrops on intraocular pressure (IOP) after cataract surgery. The effects of two
different dosage regimens, once before surgery or once before and after surgery,
were studied. PATIENTS AND METHODS: Patients scheduled for extracapsular cataract
extraction and artificial lens implantation were randomly assigned to three
groups: group A had a placebo treatment (n = 18), group B had one drop of 1%
apraclonidine 1 hour before surgery (n = 16), and group C had one drop of 1%
apraclonidine 1 hour before surgery and 1 drop at the end of surgery (n = 17).
Two percent hydroxy-propyl-methyl-cellulose was used as the viscoelastic
substance. The preoperative IOP and the IOP 6 hours postoperatively in each
patient were compared. The paired Student's t test was used to compare IOP before
and after surgery. The study design was a randomly assigned, double-masked
controlled clinical trial. RESULTS: In group A (placebo) and group B
(apraclonidine before surgery), there was a significant increase in IOP (mean IOP
increase 11.2 +/- 9.9 mm Hg SD, range -4 to 32, P = .00017, and 9.4 +/- 7.4 mm Hg
SD, range -3 to 24, P = .00014, respectively). In group C (apraclonidine 1 hour
before and immediately after surgery), the increase in IOP was not significant
(mean IOP increase 5.1 +/- 11.5 mm Hg SD, range -10 to 28, P = .084). A
postoperative IOP of more than 40 mm Hg applanation tension was reached by two
patients in group A, one patient in group B, and two patients in group C.
CONCLUSION: Although 1% apraclonidine eye-drops instilled 1 hour before and
immediately after extracapsular cataract extraction with artificial lens
implantation may help prevent a statistically significant increase in IOP after
the operation, 2 of the 17 patients still had IOPs greater than 40 mm Hg 6 hours
postoperatively. Apraclonidine applied only before surgery did not prevent a
statistically significant increase in IOP.
PMID- 9640569
TI - Topical tissue plasminogen activator appears ineffective for the clearance of
intraocular fibrin.
AB - BACKGROUND AND OBJECTIVE: To determine the efficacy of topical tissue plasminogen
activator (tPA) for the resolution of postoperative or inflammatory intraocular
fibrinous exudates. PATIENTS AND METHODS: Each treatment consisted of drops of 1
mg/ml tPA given 9 times 5 minutes apart. Records were reviewed and the results at
24 and 48 hours were recorded. Sixty-two patients had a total of 94 treatments.
RESULTS: Fibrin exudates following intraocular surgery in 34 patients were
treated 44 times. In 6 patients there was a positive result. Fibrin associated
with intraocular infection was treated in 9 patients. None showed clear
improvement. Nineteen patients had a total of 34 treatments for poorly controlled
intraocular pressure (IOP) after glaucoma surgery. Five patients showed adequate
control of the IOP, 12 did not change, and 2 had a questionable improvement.
Eleven patients had adequate IOP control after additional treatment. Seven
required suture lysis, 2 ab interno bleb revision, and 2 YAG capsulotomy or
iridotomy to reduce the IOP to an acceptable level. CONCLUSIONS: Within the
limits of this retrospective study and taking into account that fibrin may
resolve spontaneously, it appears that topical tPA drops are not effective for
the liquefaction of intraocular fibrin after surgery or in association with
intraocular inflammation. They did not improve IOP control after glaucoma
surgery.
PMID- 9640570
TI - The effect of mitomycin-C on postoperative corneal astigmatism in trabeculectomy
and a triple procedure.
AB - BACKGROUND AND OBJECTIVE: The authors attempted to determine the effect of
mitomycin-C (MMC) on postoperative corneal astigmatism in patients who underwent
trabeculectomy or a triple procedure (trabeculectomy, extracapsular cataract
extraction, and intraocular lens implantation). PATIENTS AND METHODS: Using the
vector analysis method, the authors measured the postoperative induced
astigmatism of 76 eyes in 59 patients who underwent trabeculectomy or a triple
procedure with or without the application of MMC. Postoperative induced
astigmatism corresponding to the 180 degrees axis was compared between the two
groups. RESULTS: The patients who underwent trabeculectomy with or without MMC
showed a mean induced astigmatism of -1.01 D and -2.63 D, respectively, after 1
month (P < .05), and 0.34 D and -1.42 D after 12 months (P < .05). Those who
underwent a triple procedure with or without MMC showed a mean induced
astigmatism of -1.81 D and -4.50 D, respectively, after 7 days (P < .05), and
1.73 D and -0.13 D, respectively, after 12 months (P < .05). The entire amount of
postoperative against-the-rule astigmatic shift was similar between the with-MMC
group and the without-MMC group. The against-the-rule astigmatic shift of the
group without MMC reached a plateau after 3 months. However, the group with MMC
showed continuous against-the-rule astigmatic shift until 12 months. CONCLUSION:
This study suggests that MMC induces less with-the-rule astigmatism in early
postoperative periods and continuous against-the-rule shift after 3 months
following a trabeculectomy or a triple procedure.
PMID- 9640571
TI - Long-term results of excimer laser photorefractive keratectomy in high myopia: a
preliminary report.
AB - BACKGROUND AND OBJECTIVE: To evaluate the results of 193-nm excimer laser
photorefractive keratectomy (PRK) performed on highly myopic eyes with a follow
up of at least 2 years. PATIENTS AND METHODS: Fifty-three eyes of 41 patients
were treated with a myopic PRK for an attempted correction ranging between -8 and
-17 D (mean -10.9 +/- 2.8 SD). RESULTS: The follow-up ranged from 24 to 60 months
(mean 34.1 months +/- 10 SD). Fifty-three percent of the eyes achieved a
refraction within +/- 2 D of the planned correction, with a refractive error
greater than 4 D in 21% of the treated eyes. The uncorrected visual acuity was
20/40 or better in 45% of the eyes. There were no significant opacities in 85% of
the eyes examined. A second treatment was performed on 5 eyes. CONCLUSION: The
results suggest that excimer laser PRK is a safe and relatively effective
alternative for treating highly myopic eyes, and its effects are stable over a
long period of time.
PMID- 9640572
TI - Lack of effect of prophylactic gentamicin treatment on intraocular and
extraocular fluid cultures after pars plana vitrectomy.
AB - BACKGROUND AND OBJECTIVE: To analyze the effect of preoperative prophylatic 0.3%
gentamicin sulfate eyedrops on intraocular and extraocular fluid cultures after
pars plana vitrectomy. PATIENTS AND METHODS: Forty consecutive patients
undergoing pars plana vitrectomy were randomly assigned to receive either 0.3%
gentamicin eyedrops or placebo preoperatively. Fluids from the vitreous cavity
and from the conjunctival sac were collected for bacteriologic studies. RESULTS:
Positive cultures from extraocular fluids were obtained in 30.4% of the
gentamicin group and 35.3% of the placebo group (P = .75). Furthermore, 1 (3%) of
40 cultures of intraocular fluid and 13 (33%) of 40 cultures of extraocular fluid
were positive. Culture growth positivity was not influenced by the patients' age,
by diabetes, or by the duration of the operation. CONCLUSIONS: Prophylactic
gentamicin treatment by the method applied in this study is not effective on
reducing growth positivity. Contaminated extraocular fluid may play an important
role in the pathogenesis of bacterial endophthalmitis following pars plana
vitrectomy.
PMID- 9640573
TI - In vitro evaluation of the efficacy of the capsular tension ring for managing
zonular dialysis in cataract surgery.
AB - BACKGROUND AND OBJECTIVE: In vitro evaluation of the capsular tension ring for
managing zonular dialysis in cataract surgery. MATERIALS AND METHODS: Pig and
cadaver eye models were used in this study. Lens material was removed with
phacoemulsification, then the zonules were cut in one quadrant of the meridian to
induce capsular bag decentration. Posterior chamber intraocular lenses (PC IOLs)
were implanted into the bag with or without the tension rings. The IOL and the
tension ring positions were viewed using the Miyaki technique. PC IOLs were also
implanted into isolated capsular bags with or without tension rings, and bag
configuration was examined. RESULTS: The IOL decentration was observed when the
IOLs were implanted into the eyes without zonular support in one quadrant of the
meridian. No IOL decentration was observed when the tension ring and the IOL were
implanted together. When only the IOLs were inserted into the isolated bags they
became oval, whereas the circular bags were preserved when both the IOL and the
tension ring were placed in-the-bag. CONCLUSION: The authors' in vitro model
demonstrated that the capsular tension ring maintained the circular contour of
the capsular bag and IOL centration in the eyes with broken zonules. The results
suggest that capsular tension rings may provide an alternative means to manage
zonular dialysis during phacoemulsification and PC IOL implantation.
PMID- 9640574
TI - Blood velocity in an experimental iris tumor.
AB - BACKGROUND AND OBJECTIVE: Greene strain melanoma was implanted into the irides of
eight nonpigmented rabbits to evaluate the blood flow in tumor vasculature.
MATERIALS AND METHODS: Conventional scanning laser ophthalmoscopy was used in
conjunction with fluorescent microsphere angiography (FMA). Changes were
documented on SVHS videotape for later analysis. Individual microsphere movement
was tracked through the tumor vessels. Subsequently, blood velocity measurements
were taken. RESULTS: The tumor vessels were poorly organized and inefficient.
Tumor blood velocity was up to 2.5 times slower compared with normal blood
velocity in the unaffected iris of the same eye of the same rabbit (P = .05).
Tumor blood flow could be qualitatively visualized in real time in the liver
rabbit model. CONCLUSION: The ability to visualize fluorescent microspheres
within the poorly organized tumor vasculature coupled with the reduced blood
velocity in the tumor helps to explain the success of hyperthermic tumoricidal
therapy, and may allow for development of more efficient and selective drug
delivery systems and tumoricidal agents.
PMID- 9640575
TI - Phacomorphic glaucoma associated with choroidal melanoma.
AB - Patients with phacomorphic glaucoma present with mature cataract, shallowing of
the anterior chamber, and angle-closure glaucoma. The opaque ocular media due to
cataract formation usually precludes visualization of the posterior segment of
the affected eyes. The authors describe a 65-year-old man who presented with
reduced vision and clinical findings typical of phacomorphic glaucoma.
Preoperative ultrasonography revealed an intraocular tumor, and magnetic
resonance imaging showed a high signal intensity in T1-weighted images and a low
signal intensity in T2-weighted images consistent with choroidal melanoma.
Histopathologic examination of the tumor after enucleation confirmed the
diagnosis. The clinical findings characteristic of phacomorphic glaucoma may be
associated with choroidal melanoma. Ultrasonography or other imaging studies
should be performed on eyes with phacomorphic glaucoma and opaque ocular media to
allow timely detection of any mass lesion and to guide appropriate surgical
management.
PMID- 9640576
TI - Optic nerve sheath decompression in pediatric pseudotumor cerebri.
AB - The authors report a retrospective review of two cases of optic nerve sheath
decompression in children (age younger than 16 years) and review the literature
on the procedure. Two children underwent optic nerve sheath decompression. Optic
disc edema resolved in both eyes after surgery. Some degree of visual improvement
was obtained in one eye of each patient after surgery, but one eye was unchanged
in one patient and one eye of the other patient had worsening of visual acuity
after surgery. Neither patient suffered any systemic complications from the
procedure. Of 12 patients in the literature (including these 2 patients), 66%
experienced improved visual acuity following optic nerve sheath decompression,
33% had improvement in visual field, and 17% suffered worsening of visual acuity
and visual field after surgery. Although optic nerve sheath decompression is a
relatively safe and effective treatment for visual loss due to papilledema in
adults, significant complications, including further visual loss, may occur. The
experience with this procedure in children is limited, but retrospective data
suggest that the safety and efficacy of the procedure may be comparable with that
in adult patients.
PMID- 9640577
TI - Blinding eye injury during a rock concert.
AB - A 17-year-old girl attended a rock concert where promotional compact discs were
being thrown into the audience as prizes. She suffered an extensive corneoscleral
laceration with vitreous hemorrhage and retinal detachment when a compact disc
struck her in the eye. An alternative, safer method must be used for distributing
compact discs as prizes.
PMID- 9640578
TI - Transscleral fixation of a dislocated silicone plate haptic intraocular lens via
the pars plana.
AB - A method for transscleral fixation of silicone plate haptic posterior chamber
intraocular lenses (PC IOLs) via the pars plana is described. One 10-0
polypropylene transscleral suture passed through the sclera and the PC IOL hole
and a similar suture passed through the sclera only were withdrawn outside the
eye thorough the pars plana and tied together. Pulling up the scleral end of one
suture placed the PC IOL haptic in the sulcus and the knot was pulled outside the
eye. Perfluorocarbon liquid was used during the procedure to safely manipulate
the PC IOL. The PC IOL was well centered at 3 months of follow-up. Posteriorly
dislocated silicone plate haptic PC IOLs can be safely sutured to the sclera via
the pars plana by this method.
PMID- 9640579
TI - Activities and well-being in older age: effects of self-concept and educational
attainment.
AB - The positive effect of activities on well-being is proposed to be mediated by
self-conceptualizations and facilitated by socioeconomic status. The hypothesized
processes were estimated with LISREL VIII using data from a large cross-sectional
survey with a sample of 679 adults aged 65 and older who were representative of
older adults living in the Detroit area. Findings indicate that the frequency of
performing both leisure and productive activities yields an effect on physical
health and depression and that these effects are mediated in part by a sense of
self as agentic, but less clearly by a sense of self as social. Furthermore,
socioeconomic status, operationalized as formal educational attainment,
facilitates the effect of leisure to a greater extent than that of productive
activities.
PMID- 9640580
TI - Five-year retention of the classically conditioned eyeblink response in young
adult, middle-aged, and older humans.
AB - Human participants who 5 years earlier participated in studies of acquisition of
the classically conditioned eyeblink response to a tone conditioned stimulus (CS)
and an air puff unconditioned stimulus (UCS) returned to the laboratory to test
for retention of the conditioned response (CR). Retention consisted of 20 tone CS
alone presentations. Young adult participants (23-31 years of age at the time of
retention testing) showed good retention of the CR (45%), middle-aged
participants (45-52 years) showed reduced retention (28%), and older participants
(69-78 years) showed little evidence of retention (< 5%). Retention testing was
followed by reacquisition of the CR in which the CS and the UCS were again
paired. The ability to reacquire the CR also showed a decline with age. The data
suggest that the CR can be retained over long intervals and that the degree of
retention is age dependent.
PMID- 9640581
TI - Predictors of eyeblink classical conditioning over the adult age span.
AB - The major aim was to identify predictors of the large age differences that exist
in eyeblink classical conditioning. Eyeblink conditioning was assessed in 190
participants over the age range of 20-89 years, with 150 trained in the paired
condition and 40 trained in the explicitly unpaired control condition. Timed
interval tapping was used to assess cerebellar function. Blink reaction time and
explicit learning and memory were also assessed. Stepwise multiple regression
indicated that the effect of age accounted for the largest proportion of the
variance, but the cerebellar measure also predicted eyeblink conditioning at a
significant level. Reaction time and explicit memory measures did not account for
a significant amount of the variance in eyeblink conditioning. Age-related
effects in the cerebellum apparently affect timing and learning in normal adults.
PMID- 9640582
TI - Effects of increased response dominance and contextual disintegration on the
Stroop interference effect in older adults.
AB - In the study we considered the ability of the relative speed of processing
automaticity (RSOP-A) and contextual disintegration (CD) models of the Stroop
interference effect to account for the age-related increase in Stroop
interference typically observed in older adults. Findings from the first
experiment were partially consistent with predictions of the RSOP-A model because
response dominance was greater for older adults than for younger adults. However,
the age-related increase in interference was independent of this increase in
response dominance, suggesting that factors other than those postulated in the
RSOP-A model contributed to the greater interference observed in older adults.
Results of the second experiment were consistent with the CD model, which
suggests that older adults had difficulty maintaining a color-naming strategy to
guide task performance.
PMID- 9640583
TI - The psychological refractory period: evidence for age differences in attentional
time-sharing.
AB - The authors report 2 psychological refractory period (PRP) experiments in which
the stimulus onset asynchrony (SOA) between Task 1 and Task 2 was 150 ms, 250 ms,
600 ms, and 1,100 ms for both younger and older adults. H. Pashler's (1994a)
response-selection bottleneck theory predicts that SOA manipulations should not
affect Task 1 performance, but that reaction time (RT) for Task 2 should increase
as the SOA between the 2 tasks decreases (i.e., the classical PRP effect). In
Experiment 1 (Task 1 = tone discrimination, Task 2 = dot location), older adults
showed a larger PRP effect than younger adults did, although Task 1 RT was
affected by SOA, suggesting that participants were grouping their responses on
some trials. That is, participants were holding their response for Task 1 until
they had completed processing Task 2, and then they responded to both tasks
almost simultaneously. However, a subset of participants (11 younger adults and
11 older adults) who showed no evidence of response grouping on Task 1 continued
to show a larger PRP effect for older adults on Task 2. In Experiment 2 (Task 1 =
dot location, Task 2 = simultaneous letter matching), older adults continued to
show a larger PRP effect than younger adults for Task 2, and Task 1 performance
was unaffected by SOA. Consequently, these experiments provide evidence that
older adults (relative to younger adults) exhibit a decrement in time-sharing at
the response-selection stage of processing. These results suggest that
attentional time-sharing needs to be added to the list of topics examined in
aging research on varieties of attention.
PMID- 9640584
TI - Response latencies for false memories: gist-based processes in normal aging.
AB - Three experiments have demonstrated that age-related increases in both
probability and speed of false recognitions for word lists depended on the use of
a gist-based memory strategy. When test conditions promoted a gist strategy, both
younger and older participants were as likely to falsely recognize a thematically
associated lure as to correctly recognize a studied item, and both groups were
equally fast in making these decisions. However, when test conditions
deemphasized a gist-based strategy, older adults were more likely than younger
adults, and faster, to falsely recognize both strong and weakly associated lures.
These findings suggest an age-related increase in reliance on gist-based
processing that may underlie age differences in false memory.
PMID- 9640585
TI - Stressors in highly valued roles, religious coping, and mortality.
AB - This study examines the relationships among stress, religious coping, and
mortality. It is hypothesized that religious coping will offset the effects of
stressors arising in highly valued roles on mortality, but similar stress
buffering effects will not emerge with events in less important roles. It is
further predicted that the beneficial properties of religious coping will be
especially evident among older adults with less education. Data from a nationwide
survey of older adults (N = 819; M age = 73.8 years; 41% male) indicate that
religious coping offsets the effects of stressors in highly valued roles on
mortality, but only among older adults with less educational attainment (p <
.05). In contrast, events in roles that are not valued highly do not have
significant additive effects on mortality or significant interaction effects with
religious coping.
PMID- 9640586
TI - Adult age differences in the temporal characteristics of category free recall.
AB - Two experiments are reported that examined the temporal structure of recall for
categorizable word lists by younger and older adults. All participants showed
response bursting, in which recall order is clustered by semantic category, with
longer interresponse times (IRTs) appearing between categories than within
categories. Experiment 1 demonstrated that older adults, even when matched to
younger adults in overall accuracy, differed in the rate of increase of between
category IRTs with output position, but not in within-category IRTs. Experiment 2
showed that this interaction is eliminated when the names of the response
categories are provided to the participants. Results are interpreted in terms of
combined effects of an age-compromised episodic memory system (between-category
IRTs) accompanied by a comparatively preserved semantic system (within-category
IRTs) in healthy aging.
PMID- 9640587
TI - Influences of cognitive support on episodic remembering: tracing the process of
loss from normal aging to Alzheimer's disease.
AB - Normal older adults, incident Alzheimer's disease (AD) patients, and prevalent AD
patients were examined across a 3-year interval in episodic memory tasks that
varied in terms of study time, organizability, and retrieval cues. There were
marked overall preclinical deficits among the incident AD patients, although
these patients were as effective as the normal older adults in utilizing more
study time, organizability, and retrieval cues to improve memory at baseline.
When these patients were diagnosed with AD at follow-up, they showed negligible
gains from increased study time and organizability when memory was assessed with
free recall, although they profited from the provision of retrieval cues. This
pattern of results was also seen in the prevalent AD patients at both times of
measurement. These results indicate that a general impairment of episodic memory
may precede reductions in cognitive reserve capacity in the early development of
AD.
PMID- 9640588
TI - Post-event review in older and younger adults: improving memory accessibility of
complex everyday events.
AB - Recalling an event at 1 time often increases the likelihood that it will be
remembered at a still later time. The authors examined the degree to which older
and younger adults' memory for everyday events that they watched on a videotape
was improved by later seeing photographs or reading brief verbal descriptions of
those events. Both older and younger adults recalled more events, in greater
detail, with than without review. Verbal descriptions enhanced later recall to
the same degree as reviewing photographs. Younger adults generally gained more
from review than older adults on measures of the absolute number of details
recalled and when facilitation was assessed relative to a no-review control
condition, but not when memory for reviewed events was expressed as a proportion
of each individual's total recall. Post-event review has clear potential
practical benefits for improving memory of older adults.
PMID- 9640589
TI - The effect of age, retinal eccentricity, and speed on the detection of optic flow
components.
AB - Forty observers participated in a study examining the effect of age on the
detection of motion in central and peripheral vision. Detection of lamellar
(Experiment 1) and radial flow (Experiment 2) was measured for 20 younger
observers and 20 older observers (10 men and 10 women in each group). Motion
thresholds were measured for angles of 0 degree, 10 degrees, 20 degrees, and 40
degrees off fovea. The results indicated significant differences between older
and younger adults for both motion types. The effect of age was mediated by the
gender of the observer as well as the retinal eccentricity of the display. Older
women showed higher thresholds for lamellar flow at fovea, consistent with
previous findings. The findings suggest that age-related changes in visual
information processing are affected by changes in the temporal characteristics of
the motion processing system. A model is proposed in which 2 different streams of
processing are used for the recovery and use of motion information.
PMID- 9640590
TI - Taking a computational approach to aging: the SPAN theory of working memory.
AB - The decline of working memory capacity associated with normal adult aging is well
known. What is less well established is the cause of this decline. One prominent
proposal is that working memory decline is caused by a reduction in basic
information-processing speed, but this account has lacked a demonstration that
general slowing is computationally sufficient to produce a decrease in working
memory capacity. This article presents a production system theory of working
memory (SPAN) based on established mechanisms: slowing, decay, and displacement.
Models of 2 tasks--digit symbol and computation span--which have been prominent
in research on slowing, are presented in detail. These models demonstrate that
slowing is sufficient to produce differences in these tasks, and they provide a
quantitative match to observed young-old differences as well. This advance for
slowing theory also demonstrates the viability of computational tools in aging
research.
PMID- 9640591
TI - Age, attention, expertise, and time-sharing performance.
AB - Time-sharing efficiency and resource allocation from a group of pilots with
expertise in time-sharing and a group of nonpilots (ages 20-79 years) were
examined. Participants performed 5 dual tasks that represented different degrees
of structural similarity as characterized by the structure-specific resource
model. Age, expertise, and structural similarity were found to interactively
affect time-sharing performance through attentional resources. Age-related
deficits in time-sharing were evident under conditions of intense attentional
demands and when precise control was required. Modest expertise modulation of the
age effects is likely to increase with more domain-specific time-sharing. The
structure-specific resource model provided a useful framework for interpreting
the relationship between aging and time-sharing performance.
PMID- 9640592
TI - Cancer incidence in Songkhla, southern Thailand, 1990-1994.
AB - A population-based cancer registry of Songkhla was established by the Cancer Unit
of Songklanagarind Hospital under the support of the IARC in 1990. The province
is in the southern region of Thailand and has a population of 1.2 million. This
study presents the average annual incidence rate of the provincial total and of
the district level covering 1990-1994. It is aimed at providing a comprehensive
picture of descriptive epidemiology of cancer in the province. Data were
collected from all hospitals in the provinces. Analysis was done under the
program provided by IARC. There were 3,973 invasive cancer cases in the period.
The age-standardized rate for all cancers was 116.7 in males and 88.7 in females.
Lung, oral cavity, liver, and esophagus were the main leading sites in males
while the cervix and breast were outstanding in females. By comparison, the
incidence of most cancers were lower than other registries in Thailand except for
two cancer sites. The incidence of male oral cavity and esophagus cancers in
males (ASR 10.7 and 8.5 respectively) were considerably higher. Na Mom, Hat Yai,
Sadao and Muang were districts having a high incidence of cancer.
PMID- 9640593
TI - Development of cancer registry in Phatthalung Hospital.
AB - Evaluation of feasibility is required for development of a hospital-based cancer
registry of Phatthalung Hospital. The completeness of case finding from in
hospital sources was evaluated for cancer cases diagnosed from January 1, 1994 to
December 31, 1994. Cancer patients were collected from a file of pathological
reports and medical records in Phatthalung Hospital. Items in the registration
form included identification, demographic data and the data specific to cancer.
During the same period of time, all biopsy cases sent from Phatthalung Hospital
were selected from the pathological record of the Department of Pathology,
Songklanagarind Hospital and from the database of the cancer registry of
Songklanagarind Hospital. Ninety cases with histological verification were
identified either from Phatthalung or Songklanagarind sources. Twenty seven cases
were male and 63 were female. Fifty records were identified from Phatthalung
sources and 40 additional records from Songklanagarind sources. Identification of
cancer cases only from Phatthalung sources represented only 56% of all
histologically verified cases. The two most common primary sites in males were
colon and prostate. The percentages were 18.5 and 11.1 respectively. Lung cancer
accounted only for 7.4% of all histologically verified cases. The two most common
primary sites in females were cervix uteri and breast which accounted for 31.7%
and 23.8% respectively. There was too much failure of case identification by in
hospital sources only. Songklanagarind sources were important for case findings.
However, it is important that the medical records and filing system in
Phatthalung Hospital should be improved.
PMID- 9640594
TI - Contamination of soil with parasite eggs and oocysts in southern Thailand.
AB - Soil contamination with parasite eggs and oocysts was surveyed in southern
Thailand in December 1994 and September 1995. The survey areas were Hat Kai Tao
Village in Phatthalung Province and a slum area in a city of Songkhla Province.
We used a modification of the centrifugal floatation technique with sucrose
solution (specific gravity, 1.200) to recover helminth eggs and protozoa oocysts.
Overall, 10 genera and 11 species of parasite eggs and oocysts were recovered.
They included eight species of nematoda eggs, one species of cestoda eggs, and
two species of protozoan oocysts. The definitive hosts of these parasites are
dogs, cats, sheep, lizards, humans, etc. The contamination rates in two areas at
different occasions varied from 55% to 72% with an average of 64%. Contamination
rates of Hat Kai Tao Village in beginning and end of the rainy seasons were 72%,
and 55%, respectively. Although the contamination rate in the end of rainy season
was higher than that in beginning of the rainy season, the difference was not
statistically significant (p > 0.05). Of the 11 parasites recovered, six were
infective to humans, of which, Trichuris trichura, Ascaris lumbricoides, and
Toxocara species were predominant. The mean numbers of these eggs recovered in
each test were more than 10. Therefore, the contamination was estimated to be
more than an egg per gram of soil sample based on the recovery efficiency (40%)
of this test. These results suggested that the soil in some parts of southern
Thailand may be heavily contaminated by both animal and human feces.
PMID- 9640595
TI - A case-control study of acute diarrheal disease among school-age children in
southern Thailand.
AB - We conducted a case-control study of school-age children in Phatthalung, a
province in southern Thailand using a questionnaire to investigate associations
of children's hygiene-related behavior and hygienic conditions in their homes
with acute diarrheal disease. We compared 69 acute diarrhea (less than 7 days
duration) cases that attended two hospitals in Phatthalung during August 1995 to
June 1996 with 69 age-, sex- and address-matched controls in primary schools who
had not suffered from diarrheal disease for the past one year before August 1995.
Three factors were found to be significantly associated with acute diarrheal
disease: farmer or gum planter as the occupation of father [Odds ratio (OR) 6.6;
95% confidence interval (CI) 1.7-26.1, p < 0.01], installation of a refrigerator
in children's homes (OR 0.2; CI 0.1-0.8, p < 0.05), and drinking untreated water
(OR 2.3; CI 0.9-6.1, p < 0.1). There was no significant difference for sources of
drinking water between cases and controls. Considering the data on drinking
water, the results indicated that there are some problems with quality of sources
of drinking water. The results also suggested that having a refrigerator could
have preventive effects on acute diarrheal disease, while inadequate behavior and
unhygienic environment in the homes of farmers and gum planters might be related
to acute diarrheal among school-age children.
PMID- 9640596
TI - Differential distribution of hepatitis C virus subtypes in Asia: comparative
study among Thailand, Indonesia, the Philippines and Japan.
AB - Hepatitis C virus (HCV) is currently classified into at least six major
genotypes, each of which is further divided into a number of subtypes. It has
been reported that prevalence of each subtype varies among different geographical
regions of the world and that severity of liver disease and sensitivity to
interferon treatment varies with different subtypes. The purpose of this study
was to determine and compare the prevalence of each subtype among HCV isolates in
different areas in Asia such as southern (Hat Yai) and northern (Chiang Mai)
parts of Thailand, Indonesia (Surabaya), the Philippines (Manila) and Japan
(Kobe). Sera were obtained from various groups of patients and tested for
antibodies against HCV using second and/or third generation ELISA kits. RNA was
extracted from anti-HCV-positive sera and reverse-transcribed into cDNA. The cDNA
preparations were subjected to nested PCR to amplify NS5B and 5'-untranslated
region (5'UTR) sequences. Amplified fragments were sequenced and subtypes of the
isolates were determined based on sequence similarities with reported sequences.
In Chiang Mai and Hat Yai, Thailand, HCV-3a, HCV-1a and HCV-1b were common in
various populations. HCV type 6 variants were commonly found among blood donors
and drug addicts in Chiang Mai, but not in Hat Yai. In Surabaya, Indonesia, HCV
2a was frequently detected in blood donors, but less frequently in patients with
chronic liver disease. In blood donors, HCV-1a, HCV-1b and HCV-1d were more
strongly associated with elevation of serum aminotransferase levels than HCV-2a.
HCV-1a was significantly more common in patients on maintenance hemodialysis than
in blood donors or patients with chronic liver disease. HCV-1d was detected
exclusively in Indonesia. Another unique subtype HCV-3g was found also in
Indonesia, though less frequently than HCV-1d. In the Philippines, a vast
majority of the isolates were either HCV-1a or HCV-1b. Thus, HCV subtype
prevalence varies among different regions of Asia.
PMID- 9640597
TI - Dengue viruses induce cell proliferation and morphological changes of endothelial
cells.
AB - Replication of dengue viruses (type 1, 2, 3 and 4) in vitro in endothelial cells
from human umbilical cord vein was demonstrated by virus titers and
immunofluorescent antibody studies. Both showed highest peak at Day 6 after
inoculation and declined to origin at Day 14. Some of the cultured endothelial
cells detached from the culture well. Most of these floating cells were rarely
viable as shown by failure in trypan blue exclusion whereas the adhering cells
are mostly viable. More frequent and higher intensity of immunofluorescent
positive cells were found in the detached cells as compared to adhering cells.
The virus titers in the supernatant and in the adhering cell population were
comparable, although floating cells were maximally 26.2% of the total cultured
endothelial cells. Many floating cells and occasional adhering cells had numerous
blebs on their surface. Endothelial cell proliferation was markedly increased
after virus inoculation as compared with the control. Increased number of mitotic
cells was also observed in the dengue virus-endothelial cell culture. Comparing
among the four types, dengue type 4 induced highest peaks of cell proliferation
and cell mitosis at Day 10 after inoculation. Dengue type 2 had the highest virus
titers both in adhering cells and in supernatant at Day 6 as compared with other
types.
PMID- 9640598
TI - Malaria protection in hereditary ovalocytosis: relation to red cell
deformability, red cell parameters and degree of ovalocytosis.
AB - In the culture of red cells with Plasmodium falciparum, erythrocytes from both
Thai patients and subjects (patient's parents) with hereditary ovalocytosis have
a protective effect against malarial infection. High percentage of ovalocyte (75
100%) was found in patients whereas their parents had lower percentage (25-50%).
Invasion index (II) and multiplication ratio (MR) of P. falciparum in these
abnormal red cells from the patients were significantly decreased as compared to
those in normal red cells (patients: II = 1.52 +/- 0.91, MR = 8.83 +/- 6.73;
normal subjects: II = 4.45 +/- 1.51, MR = 25.23 +/- 6.25). This suggests that the
red cells from these patients had significant degree of malaria protection. The
significant protection was also shown in red cells from the parent group (II =
1.86 +/- 0.81, MR = 15.69 +/- 3.50). Although the parents had lower ovalocyte
percentage, degree of protection against malaria parasite was as effective as
those found in patients with high ovalocytic red cells. This has been confirmed
by statistical analysis showing nonsignificant difference in II value between the
two groups. In contrast, red cells of both groups had poor deformability
(deformability index, DI) as compared to the normal group. No statistically
different DI values were demonstrated between the two. This indicates that poorly
deformable red cells, not their ovalocytic shape, make a significant contribution
to limitation of malaria parasite invasion. The MR values in patients were less
than those found in the parent group but statistical analysis showed no
significant difference. Reduced MR values were found with increased numbers of
microcytic, hyperchromic and hypochromic red cells in patients.
PMID- 9640599
TI - Recent advances in medical genetics: what we have done and what we will do.
PMID- 9640600
TI - Genomic imprinting relevant to genetic diseases.
AB - Genomic imprinting is a new concept proposed to explain unusual observations in
early mammalian development, the occurrence of certain genetic diseases, genetic
anticipation or incomplete penetrance, and tumorigenesis. The basic mechanism of
the imprinting has remained obscure, although DNA-methylation, chromatin
structure, and/or DNA replication may have a role. Genomic imprinting is a
biological phenomenon determined by an evolutionally acquired, underlying system
that may control harmonious development and growth in mammals. It is also
relevant to the occurrence of some genetic disorders in man.
PMID- 9640601
TI - Genotypic and phenotypic implications in paroxysmal nocturnal hemoglobinuria
(PNH): a preliminary investigation.
AB - The genetic and biochemical defects underlying paroxysmal nocturnal
hemoglobinuria (PNH) have recently been elucidated. The deficiency of the surface
expression of glycosylphosphatidylinositol (GPI)-anchored proteins caused by a
somatic mutation of the PIG-A gene, an X-chromosomal gene that participates in
the first step of the GPI anchor synthesis, has been shown to be responsible for
PNH in all patients. The mutations of PIG-A studied to date are highly
heterogeneous. They are however mainly of the frameshift type (61.5%). The
characteristic abnormalities of PNH phenotypes has also been shown especially by
DAF- and/or CD59-based fluorescent immunocytometry. A great degree of
heterogeneity in the patterns and levels of expression of GPI-anchored proteins
in various cell types was demonstrated indicating a discrepancy of lineage
involvement. In this investigation, major blood cell populations, i.e
erythrocytes and granulocytes were analyzed immunophenotypically, the mutations
of PIG-A were identified by heteroduplex analysis and nucleotide sequencing and
the consequences of PIG-A mutations were observed. All the mutations identified
in 9 patients with PNH resulted in complete loss of function as clones of
affected granulocytes completely negative for CD59 expression were shown in all
patients. Interestingly, granulocytes in these patients contained variable
proportions of affected cells varied from 50% to 100% and four of the patients
had erythrocytes with diminished expression of GPI-anchored DAF and CD59
coexisting with normal and completely negative cells. Immunophenotypic analysis
of reticulocytes in peripheral blood of patients with PNH demonstrated the
conserved patterns of DAF and CD59 expression in circulating erythroid cells and
the discrepancies between granulocytic and erythroid lineages. These findings
suggested that the characteristics of abnormal phenotypes which appear to be
highly variable between different hematopoietic lineages are not solely caused by
mutation of PIG-A but are influenced by other factor(s).
PMID- 9640602
TI - Pyruvate kinase deficiency in an alpha-thalassemia family: first case report in
Thailand.
AB - In Thailand, the most common cause of chronic hemolytic anemia is thalassemia
hemoglobinopathy. We report here a 10-year-old girl with pyruvate kinase (PK)
deficiency who was initially diagnosed to have Hb H disease, like her sister. The
patient had a history of neonatal jaundice which required blood exchange
transfusion twice and phototherapy. She became anemic and regular blood
transfusion was required since the age of 2 1/2 months. She was very anemic
compared to her sister and was transfusion dependent. Besides, she never had red
cell inclusion bodies, thus re-evaluation was performed. The diagnosis of red
cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved
after cessation of blood transfusion for 3 months. The family study also
confirmed the diagnosis. The patient is now on high transfusion and iron
chelation. She is doing well with mild splenomegaly.
PMID- 9640603
TI - The frequency of fragile X syndrome among selected patients at Songklanagarind
Hospital during 1991-1996, studied by cytogenetic and molecular methods.
AB - Fragile X syndrome is the most common inherited form of mental disability, world
wide. Main clinical features are cognitive deficit, speech difficulties, delayed
development, autism, and particular physical characteristics. The syndrome can be
cytogenetically diagnosed by the expression of chromosome X fragile site at band
Xq27.3. At molecular level, the cause of the syndrome is defined as an abnormal
expansion of CGG trinucleotide repeats in the 5'UTR of the FMR-1 gene as well as
hypermethylation at the proximal CpG island. Study of fragile X syndrome at
Songklanagarind Hospital during May 1991-June 1996 was herein reported. A total
of 287 blood samples of 260 unrelated families were cytogenetically examined by
using lymphocyte culture method with 2-4 different treatments. Frequency of
positive fragile X cases was found to be 7 in 260 (2.7%). Among relatives of the
positive ones, 13 individuals were also positive. Other types of chromosome
abnormalities were detected in 13 cases (5%). For molecular study, DNA samples
were obtained from 97 cases. Investigation of CGG repeat expansion was performed
by PCR method. Abnormal expansion was identified as full mutation (> 200 repeats)
and premutation (> 50-200 repeats). The abnormalities were found in 14
individuals of 5 unrelated cases; 6 with full mutation and 8 with premutation. No
molecular study on the two cytogenetic positive cases has been performed. In
conclusion, a total of 50 individuals with fragile X abnormality has been
documented: 18 affected cases and 32 carriers. Investigation of the remaining
suspected members in positive families is in progress. The information and
experience will lead to prevention of this genetic disease by prenatal diagnosis
and elective abortion in Thailand.
PMID- 9640604
TI - Screening for thalassemia: an economics viewpoint.
AB - Thalassemia presents individual, social and economic burdens: a key question is
whether medical and economic viewpoints converge or not. Using precise molecular
probes, prenatal diagnosis of the various thalassemia genotypes is available in
the case of parents who are known carriers, so identified because of a previous
affected child or a positive family genetic history. However, the ideal option of
prevention of the birth of a first affected child requires community screening.
The only practical approach thereto is prenatal screening of women in early
pregnancy at ante-natal clinics (ANC). The initial steps (OF, DCIP) are simple,
cheap and easily coupled with standard prenatal procedures. In the second phase,
spouse screening, compliance is suboptimal and involves non-routine opportunity
costs. Subsequent steps (secondary screening of positive pairs, genotyping of
positives, and fetal diagnosis [PND]) represent greater costs to provider and
consumer, and, as they are relatively expensive, reduced compliance at each step
if the major part of the economic burden (direct and indirect costs) is to be
borne by the consumer. Thus, only a proportion of cases is likely to face the
final decision to terminate pregnancy or not. Some broad estimates of costs of
each phase (ANC-->PND) have been made for comparison with the estimated costs of
case management of the several thalassemia disease classes for their projected
lifetimes, while several more detailed studies are in progress to fine tune the
real costs (direct and indirect) of diagnosis. In a purely economic sense the
situation presents opportunity to consider trade-offs between PND and disease
case management, in terms of benefit:cost ratio. Viewed from a health systems
vantage point this ratio depends substantially on compliance, as the system must
consider the cost of caring for all thalassemia cases, including those births
which could have been avoided by optimal compliance. In ideal circumstances the
rough estimates indicate a probable benefit:cost ratio > 1, supporting the notion
of community-based screening. Such a result, however, compares procedures in a
short, finite time frame (diagnosis) with a less predictable, longer life-time
(case management), requiring bureaucratic flexibility (if the public provider is
to pay) or family emotional/fiscal investment (if the consumer is to pay) or both
(cost-sharing): either way there is an inescapable element of long term
investment planning that requires squaring off of the emotional, social and
fiscal ingredients in the equation. In this sense the thalassemia syndromes
represent an example of decision-making pathways involved in assessing and
handling chronic disease burdens at family, community and national levels: at the
latter level regional incidence varies considerably, a geopolitical factor which
may require differential demographic planning.
PMID- 9640605
TI - An in vitro study on thalassemic erythroid precursors in liquid culture.
AB - Thalassemia is an inherited hematological disorder which can generally be
classified according to the affected globin imbalance (alpha- or beta-globin)
into two main types, i.e. alpha-thalassemia and beta-thalassemia, respectively.
There is a wide range of cellular abnormalities associated with thalassemic
erythrocytes such as hypochromia, microcytosis, reduced cellular deformability
and membrane oxidative damage. The red cell abnormalities lead to premature
destruction with marrow erythroid hyperplasia and ineffective erythropoiesis. The
abnormalities in thalassemic red blood cells have been found along the erythroid
differentiation pathway other than the mature stage as previously shown in bone
marrow erythroid precursors and in reticulocytes, the penultimate stage of
erythroid differentiation. However, there is a lag in our understanding of the
more primitive erythroid stages due to the difficult and hazardous marrow
aspiration and heterogeneity of cells derived. We have utilized a novel method of
Two-Phase Liquid Culture (TPLC) of beta-thalassemia/HbE erythroid precursors
instead of conventional semisolid culture. This type of liquid culture can given
higher cell yield with quite synchronous cell differentiation stages and easily
be applied for other cellular analytical techniques. The peripheral blood
mononuclear cells (PBMC) obtained from non-splenectomized and splenectomized beta
thalassemia/HbE patients were first cultured in medium supplemented with 5637
conditioned medium for a 6-day period (phase I) and then transferred to medium
supplemented with recombinant human erythropoietin to allow the terminal
differentiation of erythroid precursors (phase II). During the phase I or II, the
cultured cells were periodically sampled to determine the cell number,
cytocentrifuged on glass slides and stained with Wright stain for morphological
assessment of their differentiation stages and analyzed flow cytometrically by
staining with fluoresceinated anti-transferrin receptor (anti-CD71) and R
phycoerythrin-conjugated anti-glycophorin A. After assessment by flow cytometry,
the remaining stained cells were cytocentrifuged on glass slides and photographed
by a fluorescent microscope and a laser scanning confocal microscope. The results
of morphological assessment, flow cytometric analysis and microscopic pictures
will be presented.
PMID- 9640606
TI - Alpha-thalassemia incidence in southern Thailand by restriction endonuclease
analysis of globin DNA from placental blood at Songklanagarind Hospital.
AB - The incidence of alpha-thalassemia has been studied previously based on the
levels of Hb Barts' in cord blood. This method is an inadequate indicator of
alpha-thalassemia. Thus in this study we use DNA analysis to get more accurate
data. Hb Barts' was detected in placental blood samples from 15.5% of 375 infants
born at Songklanagarind Hospital. The white blood cell DNA of 300 samples was
studied for alpha-globin gene deletions by hybridization of DNA fragments
digested by the restriction endonuclease Eco RI with specific 32P-labled zeta
globin gene probe. The incidence of alpha-thal 2 and alpha-thal 1 traits were
12.0% and 4.3%, with the gene frequencies 0.0650 and 0.0217 for -alpha/and --/,
respectively. The incidence of HB CS trait was 5.8%, with the gene frequency of
0.0292 for alpha cs alpha/. We also found that the incidence of the triplicated
zeta and triplicated alpha were 14.7 and 1.0%, with the gene frequencies of
0.0733 and 0.0050 for zeta zeta zeta/and alpha alpha alpha/, respectively. The
DNA lesion of alpha-thalassemia in the south is similar to the study of
Tanphaichitr et al (1988) in central Thailand. Knowledge of alpha-globin gene
deletion would be useful for prenatal diagnosis of Bart's hydrops to prevent
toxemia of pregnancy in the south of Thailand.
PMID- 9640607
TI - Red cell parameters in alpha-thalassemia with and without beta-thalassemia trait
or hemoglobin E trait.
AB - Eighty-five patients who attended at Ramathibodi Hospital during November 1994 to
June 1996 were investigated for thalassemia genotype, hemoglobin (Hb) typing and
blood cell parameters. All patients were screened primarily for complete blood
count using the Technicon H*3 automated hematology analyzer and Hb typing using
the automated HPLC. Their genotypes were evaluated by in vitro gene amplification
using primers for detection of common alpha-thalassemic genes found in the Thai
population. We found 45 cases out of 85 were alpha-thalassemia trait with A2A
typing, 10 were normal, 7 were alpha-thalassemia trait complicated by beta
thalassemia trait or HbE trait, 18 were HbH disease or HbH with Hb Constant
Spring (HbH/CS), and 5 were AE Bart's disease. The alpha-thalassemia 1 trait had
heterogeneity in red cell population as shown by increased red cell distribution
width (RDW), the increased percent microcytic red cell (%Micro) and decreased
mean cell volume (MCV). Red cell parameters in alpha-thalassemia 2 trait and HbCS
trait were not significantly different from normal. The cases with coinheritance
of alpha-thalassemia trait with beta-thalassemia trait or with HbE trait showed
variation in their red cell parameters: one case showed less abnormal red cell
parameters than those of uncomplicated alpha-thalassemia but the other two cases
showed unimproved values. The homozygous alpha-thalassemia 2 showed similar red
cell parameters to the alpha-thalassemia 1 trait. In conclusion, we can screen
the alpha-thalassemia 1 trait and homozygous alpha-thalassemia 2 by using the
simple red cell parameters such as the MCV and RDW; however, they must be
confirmed for alpha-thalassemic genes. Unfortunately, red cell parameters of
alpha-thalassemia 2 trait or HbCS trait were not different from those of normal
subjects.
PMID- 9640608
TI - Molecular and hematological characterization of HbE heterozygote with alpha
thalassemia determinant.
AB - Hemoglobin E and alpha-thalassemia are prevalent in Thailand. The chance that an
individual heterozygous for HbE also carries an alpha-thalassemia determinant is
high. In this individual, the amount of HbE and other hematological parameters
may be differed from that of usual observation. In this study, a total of 132 HbE
heterozygotes were screened for alpha-thalassemia 1 gene deletion by the
polymerase chain reaction. Out of 132 cases, 71 could be completely analyzed for
hematologic parameters. Forty-three of 88 cases with HbE less than 25% as
measured using microcolumn chromatography were positive for this gene deletion.
In twenty of these 43 alpha-thalassemia 1 positive cases, the average values of
Hb, Hct, MCV, MCH, MCHC, RDW and HbE were 10.6 g/ dl, 33.1%, 64.8 fl, 21.0 pg,
32.3 pg/dl, 18.6% and 17.4%, respectively. Eight of 9 alpha-thalassemia 1
negative cases were positive for alpha-thalassemia 2 gene deletion in Southern
blot analysis. In this later group, hematological parameters were similar to that
of the former. Co-inheritance of the Hb Constant Spring gene has no direct effect
on the level of HbE. No alpha-thalassemia 1 gene was detected in the remaining 34
cases whose HbE were above 25%. The average amount of Hb, Hct, MCV, MCH, MCHC,
RDW and HbE were 12.4 g/dl, 37.7%, 79.7 fl, 26.2 pg, 32.7 pg/dl, 25.8% and 28.5%,
respectively. Therefore, screening for HbE level below 25% may be a convenient
way of identifying parents of carrying alpha-thalassemia 1 determinant.
PMID- 9640609
TI - Molecular basis of beta-thalassemia in Thai Muslim patients in the the south of
Thailand.
AB - Among a sample of 29 unrelated Thai Muslim children, a total of 37 beta
thalassemia genes was identified and 33 out of 37 mutations (89%) were
characterized giving 6 different mutations. Four mutations [IVS-1 nt 5 (G-C),
codon 19 (A-G), codons 41/42 (-CTTT) and IVS-1 nt 1 (G-T)] account for 86%. IVS-1
nt 5 (G-C) is the most common mutation found in Thai Muslim patients. Thai Muslim
patients share the four most common mutations with Malays.
PMID- 9640610
TI - Clinical, hematological and molecular features in Thais with beta-Malay/beta
thalassemia and beta-Malay/HbE.
AB - A total of 50 patients and relatives were studied comprising 12 cases of compound
heterozygosity of beta-Malay and beta + thalassemia, 10 cases of compound
heterozygosity of beta-Malay and beta degree thalassemia, 10 cases of beta-Malay
and HbE and 18 cases of beta-Malay heterozygosity. Patients with beta-Malay and
HbE had very mild clinical symptoms or were asymptomatic of thalassemia disease
in the absence of blood transfusion. Homozygosity of beta-Malay produce mild
clinical symptoms of thalassemic disease with normal facial characteristics and
were not transfusion dependent. Patients with beta-Malay and IVS 1 nt 5 (G-C) had
severe clinical symptoms, and were transfusion dependent. Patients with beta
Malay and beta degree thalassemia had severe clinical symptoms, delayed weight
and height in relation to age, were transfusion dependent and had classical
features of thalassemic diseases.
PMID- 9640611
TI - Molecular and hematological characterization of Hb Tak and Hb Pyrgos in Thailand.
AB - Two hemoglobin variants that migrate abnormally on gel electrophoresis were found
in four unrelated Thai individuals. One variant that migrate faster than HbA but
more slowly than Hb Bart's was detected in two heterozygotes. Another abnormal Hb
migrating between HbA2 and HbF was found in one heterozygote and one compound
heterozygote with HbE. In all cases, no microcytic anemia was observed. PCR
amplification and direct DNA sequencing established that the first variant was
caused by a missense mutation at codon 83 (GGC-GAC) that leads to Gly to Asp
substitution previously described as the Hb Pyrgos in a Greek boy. The second
variant was caused by an AC insertion at the termination codon that leads to
synthesis of elongated beta-globin chain known as the Hb Tak. Beta globin gene
haplotype analysis demonstrated that each variant was found on the same
chromosome background in Thai individuals. The simple non-radioactive DNA assays
based on allele specific polymerase chain reaction for the detection of these two
Hb mutations in a routine laboratory are described.
PMID- 9640612
TI - Beta-globin gene haplotypes in some minor ethnic groups in Thailand.
AB - In order to provide population genetic data of various ethnic groups in Thailand,
we have determined the type of hemoglobin by electrophoresis and the beta-globin
gene haplotypes by PCR followed by restriction digestion in five small ethnic
groups namely hill tribes, PhuTai, Chong, Lao Song and Sakai inhabiting in the
north, northeast, east, central and south of Thailand, respectively. In each
group, in addition to HbA and HbA2, the HbE, the most common hemoglobinopathy in
Southeast Asia was detected at 2.5%, 51.6%, 84.0%, 8.6% and 11.8%, respectively.
Haplotype analysis demonstrated that in all groups the beta A-globin gene was
associated with various haplotypes and beta-globin gene frameworks. However, beta
E -globin gene was associated with haplotypes ((-)+(-)+ + +(-)) and ((+)-(-)-(
)+(-)) on the beta-globin gene framework 2 in all ethnic groups except in Chong
people whose the beta E-globin gene was mostly linked to haplotype ((-)+(-)++(
)+) and beta-globin gene framework 3 which was commonly found among Cambodian. It
appears therefore that the Chong population is more related to Cambodian than
Thai.
PMID- 9640613
TI - Analysis of beta-thalassemia mutations and beta-locus control region
hypersensitive sites 2, 3 and 4 in southern Thailand.
AB - beta-Thalassemia mutations in 221 chromosomes of unrelated southern Thai patients
were analyzed. Using dot blot hybridization of PCR amplified DNA with 15 allele
specific oligonucleotide probes for beta-thalassemia mutations 196/221 (89%) of
the alleles were characterized. Ten mutations were identified, of which six
[codon 41/42 (TTCTTT-TT), IVS1 nt5(G-C), codon 19 (AAC-AGC), codon 17 (AAG-TAG),
IVS1 nt1(G-T), -28 TATA (A-G)], accounted for 85%. Among the 25 uncharacterized
alleles, 15 were analyzed by automated fluorescent DNA sequencing of the whole
beta-globin gene with normal results in 7 alleles. Four mutations, previously
described were detected in 8 alleles. They were a G-A at IVS1 nt1 in one
heterozygote, a G-T at IVS1 nt1 in one heterozygote, codon 15 (TGG-TAG) in two
heterozygotes and poly A(AATAAA-AATAGA) in two homozygotes. The polyadenylation
mutations, previously demonstrated in the Malaysian population have been first
detected in Thailand. It is remarkable that the IVS1 nt1 (G-A) mutation,
previously reported in the Mediterranean population has been found only in the
south of Thailand. This mutation was probably imported from Portugal. In former
times the Portuguese had settled in Phuket in southern Thailand. In order to find
a causative mutation in the rest of 7 true unknowns we performed direct DNA
sequencing of the core fragments of the beta-Locus Control Region Hypersensitive
Sites (LCR HS) 2,3 and 4 in these 7 samples. DNA sequencing of HS2 and HS3
fragments showed normal results. The heterozygote A/G was present in the
palindromic sequence of the LCR HS4 (TGGGGACCCCA) in 6 beta-thalassemia samples.
The same heterozygote A/G was found in 5/12 normal subjects. The allele frequency
of A (0.79) is obviously higher than that of G (0.21). This could be due to the
stability of the palindromic structure. When an A is in the middle of the
palindromic sequence, the hairpin structure is formed. In contrast the hairpin
structure disappears when a G is in the middle of the palindromic sequence. This
structure is not further symmetric and may not be so stable as the hairpin
structure. beta-Thalassemia mutations in southern Thailand are very heterogeneous
and their distribution is different from other parts of the country.
PMID- 9640614
TI - Detection of thalassemia genes using smeared blood film or leukocytes adhering to
polysthylene fibers.
AB - Presently genetic analyses for thalassemia types require relatively large amounts
of heparinized blood (5 to 10 ml), and transport as well as degeneration of these
sample is a problem in the developing world. We have developed a new method to
simplify this procedure and obtain DNAs from small specimens. As experimental
materials, thinly smeared blood on a glass slide or blood filtered with and
adhered on polysthylene telephtalate (PST) fibers were used. These materials
could be safely stored without interfering with DNA extraction for up to 3
months. The slide materials were digested with proteinase K, and DNA was
extracted with Tris-EDTA-phenol:chloroform and precipitated with absolute
ethanol. The PST specimens were washed with physiologic saline and treated in the
same manner as described above. Products were easily amplified by PCR and
digested with restriction endonucleases for beta thalassemia typing as well as
for HLA-DQA1 gene typing. Results obtained by this method correlated well with
previously reported incidences for thalassemia and HLA-DQA1 types in Thailand.
This method can be used in the routine laboratory because it allows for stable
and biosafe genetic analyses.
PMID- 9640615
TI - Difference in pattern of erythropoietin response between beta
thalassemia/hemoglobin E children and adults.
AB - Thalassemia is one of the most common genetic disorders in Thailand. The
thalassemic patients have many pathophysiologic changes secondary to chronic
anemia. During these last few years there have been many trials to cure or
improve the anemic condition in thalassemia by using various agents, including
erythropoietin (EPO). Thus it is very important to understand the EPO response to
different degree of anemia in the thalassemic patients. In this study we
evaluated the EPO status in 53 beta-thalassemia/HbE patients, from 4-61 years
old, by enzyme-linked immunosorbent assay. The results showed that the levels of
EPO in beta-thalassemia/HbE patients were much higher than in normal control
subjects: mean +/- SE = 527 +/- 183.20 and 3.45 +/- 0.47 mIU/ml respectively. The
reverse correlation between the levels of EPO and hematocrit (r = -0.704) was
also observed. There was also a tendency to have higher levels of EPO in beta
thal/HbE children than in adults, although this was statistically insignificant.
The observed versus predicted levels of EPO (log O/P ratio) showed that most
patients had good EPO response to the degree of anemia. However, inappropriate
decrease of EPO response was observed in 8/40 adult patients. The EPO levels in
these patients were not correlated with any physical or laboratory studies,
including kidney function. We thus propose that if EPO is to be considered as one
of the alternative treatment to the thalassemic patients, in the future, it may
benefit only the patients with low EPO levels.
PMID- 9640616
TI - Pulmonary microthromboembolism by injection of sonicated autologous blood in
rabbits with splenic artery ligations.
AB - Chronic pulmonary thromboembolism (PTE) has been reported to play an important
role in cardiac failure in thalassemic patients after splenectomy. However, the
mechanism of PTE in these patients remains unclear. In this study, we attempted
to establish an animal model of PTE seen in thalassemic patients after
splenectomy. We divided New Zealand white rabbits into three groups: Group 1 was
injected sonicated blood, II was injected non-sonicated blood after ligation of
the splenic artery, and III was injected sonicated blood after ligation of the
splenic artery. After injection of the sonicated blood, we counted the platelet
number until 1 hour and the rabbits were sacrificed for histological examination.
Platelets significantly decreased in number immediately after injection of the
sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly
of platelets were found in Group III but not in other groups. These pathological
changes seem to be partly similar to those of thalassemic patients after
splenectomy. This animal model is thought to be useful to study the pathogenesis
of pulmonary thromboembolism, especially in thalassemic patients after
splenectomy.
PMID- 9640617
TI - Possible evidence of endothelial cell activation and disturbance in thalassemia:
an in vitro study.
AB - Activation of vascular endothelium is considered as an important facet of
inflammation, thrombosis, and vasculitis. Activated endothelial cells express a
number of immunologically relevant surface markers which are not detected in
dormant condition. These surface markers on endothelial cell may involve in
adhesion reaction and migration of blood cell components. We demonstrated
increased level of the soluble adhesion molecules in circulating blood of both
alpha- and beta-thalassemic patients. These adhesion molecules are theoretically
known to be released from endothelial cells. The adhesion molecules included
soluble Intercellular Adhesion Molecule-1 (sICAM-1), soluble E-Selectin (ELAM-1),
soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), and von Willebrand Factor
(vWF). The levels of these adhesion molecules were measured in serum from 32
thalassemic patients and 10 control healthy subjects. As compared to normal,
increased sICAM-1 was found in beta-thal/HbE patients with non-splenectomy; BE-NS
(p = 0.002), increased ELAM-1 in beta-thal/HbE patients with splenectomy; BE-S (p
= 0.01) and HbH with Hb Constant Spring; HbH/CS (p = 0.001), and increased sVCAM
1 in BE-NS; (p = < 0.0001) and BE-S (p = 0.002). Significant increase in von
Willebrand Factor (vWF), a marker for endothelial cell, was shown in BE-S (p =
0.04) as compared to normal. Adhesion molecules were also markedly demonstrated
in the supernatant of in vitro culture of human vascular endothelial cell in the
presence of 30% thalassemic serum, and these adhesion molecules were also
detected on the surface of the cells by using the technic of laser scanning
confocal microscope and direct immunofluorescence.
PMID- 9640618
TI - Morphological alterations and apoptosis of endothelial cells induced by
thalassemic serum in vitro.
AB - Vascular complications such as lung thromboembolism and leg ulcer have been
observed in thalassemic patients. Recently, our group has reported impaired
proliferation of endothelial cells (ECs) after exposure to alpha- and beta
thalassemic sera in a culture system. This study was undertaken to detect
apoptotic phenomena of ECs in the presence of alpha- and beta-thalassemic serum.
ECs from normal human umbilical cord vein were exposed to 30% thalassemic serum
in vitro and morphological changes were observed by using phase contrast,
fluorescence and scanning electron microscopy. Such treated ECs presented
morphological characteristics of apoptosis as shown by the appearance of compact
cytosol, membrane blebbing, margination of nuclear matrix, condensed nuclei, and
fragmented bodies. The majority of apoptotic cells was in the floating
population. Similar morphological changes were also observed by treating ECs with
hydrogen peroxide in the concentration range of 0.1-10 mM.
PMID- 9640619
TI - Thalassemic serum inhibits endothelial cell mitosis in vitro.
AB - Human umbilical vein endothelial cells were cultured in vitro using Iscove's
Modified Dulbecco's Medium (IMDM) supplemented with either pooled normal human
serum, or pooled thalassemic serum, or autologous umbilical cord serum, or fetal
bovine serum. The mitotic activity was determined under the inverted phase
contrast microscope and the number of mitotic cells was counted. Our results
showed that the mitotic cells decreased in endothelial cell culture with
thalassemic serum as compared with normal human serum, autologous umbilical cord
serum or fetal bovine serum. The percentage of mitotic cells decreased on day 3
in the presence of beta-thalassemia/HbE serum from both splenectomized and non
splenectomized patients as compared with normal or autologous umbilical cord
serum. In the presence of alpha-thalassemic serum, a similar outcome was also
observed. From this study we can conclude that the thalassemic sera might contain
factors which affect the endothelial cell growth and proliferation by inhibiting
mitosis in vitro.
PMID- 9640620
TI - A simple and quantitative method for the determination of tissue factor.
AB - Tissue factor (TF), a potent initiator of the extrinsic coagulation pathway, is
believed to have a critical role in thrombogenesis and haemostasis. To elucidate
the role of TF in the development of various syndrome, we developed a
quantitative assay method for the determination of TF using FIX complex
(Profilnine) and the synthetic chromogenic substrate S-2238, all of which are
commercially available. The method is simple, very sensitive, good linearity and
applicable to the tissue culture plate, indicating its promising usage for the
quantitation of TF activity of cells.
PMID- 9640621
TI - Surface and total tissue factor activity of endothelial cells.
AB - With a technic that was developed by us, we found that normal human umbilical
vein endothelial cells (HUVEC) in culture characteristically had very little
tissue factor (TF) activity either on the surface or in the cells which had been
disrupted. In the presence of endotoxin (E. coli O26:B6), a trigger for
thrombosis in septicemic patients, we could not detect an increased TF activity
of HUVEC on its surface. However, an increase in TF (total TF) was detected after
disruption of the cells. The increase in total TF was dose-dependent. Endotoxin
at the concentration of 10 micrograms/ml caused around 5 fold increase in total
TF activity compared to that of HUVEC in the absence of endotoxin.
PMID- 9640622
TI - A double-blind placebo control trial of dilazep in beta-thalassemia/hemoglobin E
patients.
AB - Since the obtained results from the pilot study indicated that dilazep which was
a membrane stabilizer would be benefit to treatment and prevention of anemia and
chronic leg ulcer in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients, the
authors had continued the study in a second phase, ie a double blind placebo
control trial. Twenty-seven beta-thal/HbE patients were recruited in the study.
Eight patients who suffered from chronic leg ulcer were given dilazep. The rest
of patients were given dilazep or placebo according to a randomized table. Hence,
16 patients received dilazep and 11 received placebo. When we compared the number
of unit of blood transfusion, hemoglobin level, 2-3 DPG and P50 value between the
dilazep and placebo groups using unpaired t-test, we found that there were no
statistical differences in any of the parameters. However, when we compared the
data within the group using paired t-test, there was statistical decrease in
blood requirement after treatment in the dilazep group (p < 0.05). Concerning
with the treatment of chronic leg ulcer, 3 in 8 patients were completely healed
within 3 months, 4 in 8 patients were improved and 1 in 8 patients was not
improved. There were complaints of skin itching and mild epigastric pain in
placebo group but the liver function tests, kidney function tests and cardiac
enzyme did not significantly change during the medication.
PMID- 9640623
TI - Risk factors for chronic rejection--a clinical perspective.
PMID- 9640624
TI - Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of
pig kidneys and livers.
AB - Organ perfusion is one of the possible strategies to attenuate rejection of
discordant xenografts by reducing the levels of the recipient's xenoreactive
natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in
models of primate blood or plasma perfusion through porcine kidneys or livers,
with special attention to haematological consequences and potential side-effects.
We first perfused the blood of rhesus monkeys through pig kidneys and livers, and
demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption
(72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we
normalized for the weight of the perfused organs and for levels of natural
antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U
antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of
rejection were observed in perfused kidneys, but not in perfused livers. A major
drawback of the perfusion of blood through livers was a considerable decrease in
the primates' haemoglobin and platelet levels. To avoid this, we developed a
plasma liver perfusion device. This method allowed a significant improvement in
the haemodynamic state of primates and was particularly effective in preventing
anaemia. Moreover, plasma liver perfusion was as effective as blood liver
perfusion to remove natural antibodies and, resulted in a marked decrease in
their functional activity as assessed by complement-dependent cytotoxicity (CDC)
and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other
plasma proteins was not significantly affected, apart from a dilution effect.
After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and
ADCC between days 7 and 14 and then decreased progressively. We conclude that the
separation of blood to allow the perfusion of plasma through a pig organ is safer
than the perfusion of unseparated blood and is associated with efficient natural
antibody removal. However, organ perfusion is limited by a rebound in antibody
levels after a few days, and thus will have to be associated with anti-B cell
immunosuppressive therapy for long-term or repeated applications.
PMID- 9640625
TI - Mycophenolate mofetil reduces production of interferon-dependent major
histocompatibility complex induction during allograft rejection, probably by
limiting clonal expansion.
AB - The immunosuppressive drug mycophenolate mofetil (MMF) acts by releasing
mycophenolic acid (MPA), which inhibits the enzyme inosine monophosphate
dehydrogenase (IMPDH) and thus inhibits de novo purine synthesis. Unlike
cyclosporine (CsA), MMF has no direct effect on cytokine gene expression in
vitro. We examined the effect of MMF, in comparison to CsA, on in vivo production
of interferon-gamma (IFN-gamma) in mice. Two stimuli for IFN-gamma induction were
used: (1) allogeneic P815 mastocytoma ascites tumour cells and (2) bacterial
lipopolysaccharide (LPS). The allogeneic response is dependent on clonal
expansion of T cells, while the LPS response is polyclonal and T cell
independent. Since major histocompatibility complex (MHC) induction in mouse
kidney is IFN-gamma dependent, we assessed the in vivo induction of IFN-gamma
indirectly by measuring MHC induction in mouse kidneys in three systems:
radiolabelled antibody binding assay, immunoperoxidase staining in tissue
sections, and Northern blotting for steady-state MHC mRNA levels. IFN-gamma
steady-state mRNA levels were assessed by reverse transcriptase polymerase chain
reaction (RT-PCR). In the allogeneic response, MMF (40-160 mg/kg/day) reduced the
production of IFN-gamma in a dose-dependent fashion. MHC class I and II induction
was reduced by 35% to 74% and 30% to 74%, respectively. However, MMF had less
effect on the induction of MHC by a nonimmune stimulus, bacterial LPS, whereas
CsA reduced the induction of IFN-gamma in both responses. We conclude that MMF
reduces the IFN-dependent induction of MHC in vivo during specific immune
responses, probably by limiting clonal expansion, while preserving nonspecific
cytokine production in response to LPS.
PMID- 9640626
TI - Mutual tolerance after liver and not after heart transplantation? Evaluation of
patient-anti-donor and donor-anti-patient responses by mixed lymphocyte culture.
AB - The ultimate goal in organ transplantation is the induction of donor-specific
transplantation tolerance. The fact that in some patients it is possible to
withdraw immunosuppressive therapy completely, suggests that immunological
adaptation or donor-specific nonresponsiveness can occur following
transplantation. In earlier studies we have shown that after blood transfusion,
the mixed lymphocyte reactivity of the donor against patient peripheral blood
mononuclear lymphocytes taken after blood transfusion gradually decreased with
time. This may reflect the induction of an immunoregulatory mechanism, which
protects the recipient against an immune reaction of the donor, enhancing a state
of mixed chimerism. A similar phenomenon might also play a role in the
immunological mechanism leading to transplantation tolerance. Therefore, we
studied responses in patients with a well-functioning liver and heart transplant
using a primed lymphocyte test (PLT) and a mixed lymphocyte culture (MLC). Two
years after liver transplantation the PLT and MLC responses of patient against
donor were decreased significantly compared to the situation before
transplantation. The response of donor against patient was also lower two years
after transplantation. The decreased responses were donor-specific since
responses to third-party cells generally remained unchanged. In heart transplant
recipients we could not detect a donor-specific downregulation. The reversed
response, of donor against patient, was not different from responses of third
party against patient cells. Therefore, we conclude that donor-specific
nonresponsiveness is not induced in patients with well-functioning heart
transplants. In contrast, after a successful liver transplantation the response
of patient against donor is decreased, as is the reversed response. It may be
valuable to test whether in liver transplant patients withdrawing or reducing of
maintenance immunosuppression is permitted for patients who appear to have
developed two-way donor-specific hyporeactivity.
PMID- 9640627
TI - Pattern of cytokine expression in circulation CD57+ T cells from long-term renal
allograft recipients.
AB - We made a quantitative analysis of the lymphokine mRNA and of proteins produced
by CD57+ and CD57- circulating T cells isolated from long-term kidney
transplanted patients with expanded CD4+/CD57+ and CD8+/CD57+ T cells, and from
normal individuals. We concentrated on IL-2 and IFN-gamma, which define a Th1
like type of lymphokine production, and on IL-4 which defines a Th-2-like type.
We also analysed the production of IL-10 which is endowed with inhibitory effects
on IL-2 and IFN-gamma synthesis, and of TNF-alpha, a pleiotropic inflammatory
cytokine. On ionomycin + PMA stimulation, which reveals the intrinsic potential
of lymphokine production by T cells, the CD57+ T cell subsets from all
individuals produced high amounts of IFN-gamma and TNF-alpha mRNA and protein.
They also produced IL-2, but to a much lesser extend than their CD57-
counterparts, and little IL-4 and IL-10. They were no more capable of producing
IL-2 when stimulated through the CD3/TCR in the presence of monocytes, yet still
synthesized IFN-gamma. Our data suggest that the in vivo expansion of CD57+ T
cells in stable allograft renal recipients might correspond to Th1 energized
cells which on triggering of cell surface receptors hardly secrete lymphokines
involved in cell cycle progression, but can still exert some effector functions,
including IFN-gamma secretion.
PMID- 9640628
TI - Effect of leflunomide and cyclosporine on graft survival and changes in
lymphocyte phenotypes in a rat heart allotransplantation model.
AB - Cyclosporine-A (CSA) and leflunomide (LF) can delay or prevent organ graft
rejection. We investigated the combination of LF, CSA and splenectomy on graft
survival and changes in lymphocyte phenotypes (LP) in a rat allotransplantation
model. In the study 19 Lewis rats were splenectomized prior to heterotopic heart
transplantation. SPRD rats served as donors. The recipients were divided into
three groups: A--five animals received CSA and LF for two weeks, B--five received
intermittent CSA and LF for the whole investigation period and C--nine received
no drug therapy. LP was quantified relatively by flow cytometric analysis. We
found that graft survival was longer in group A (median 155 days, range 52-348)
and B (341, range 338-342), compared to group C (8, range 7-13). The histological
examination, however, revealed signs of rejection in all allografts. In group A
all except one animal and in group C the morphological changes were characterized
by severe acute rejection. In contrast, one animal in group A and all the animals
in group B revealed signs of moderate acute rejection and in most animals signs
of chronic rejection were also found. The reduction of Pan-T and CD4+ cells in
group B compared to the control group was associated with no clinical rejection,
while the increase of CD8+ cells in group C and partly in group A (except for
animal 3) was associated with clinical rejection. No difference in LP was
detected between groups A and B in the study period. We concluded that a
combination of CSA, LF and splenectomy was efficient in preventing clinical
rejection, however, there were signs of rejection morphologically even in animals
without clinical rejection. The changes in LP over time could not predict the
clinical outcome. However, increase in CD8+ cells was highly associated to
clinical rejection among nonimmunosuppresed animals.
PMID- 9640629
TI - The effect of anti-CD3-immunotoxin on T lymphocyte function in vitro.
AB - Recent advances in the design of immunotoxins (IT) have yielded significant
improvements. FN18-CRM9, a construct of anti-CD3 epsilon mAb FN18 and mutated
diphtheria toxin CRM9 has exhibited high specificity, low systemic toxicity and
unusual efficacy compared to previous iterations of immunotoxins. Others and we
have examined this anti-CD3-IT for the purpose of inducing immunological
tolerance through selective ablation of T cells in rhesus macaques and have
obtained encouraging results. In order to characterize its mode of action, we
have examined its effects on peripheral blood and lymph node T cell killing in
vitro. We have studied the cytotoxic mechanism induced by this anti-CD3-IT as
well as its effects on proliferation, phenotypic changes and cytokine production
(IL2, IFN gamma and TNF alpha). The results indicate that anti-CD3-IT was highly
specific for T cell killing at doses as low as 1 x 10(6) micrograms/ml and showed
a maximal effect at 48 h after exposure. The toxicity was restricted to T cells,
as B cells and other bystander cells were spared. This immunotoxin was shown to
induce T cell apoptosis, as assessed by TUNEL assay, DNA content and
cytotoxicity. Fas expression was upregulated on T cells within 24 h after in
vitro exposure to anti-CD3-IT, suggesting an early T cell activation phase prior
to T cell death. T cell killing was manifest as an early cell cycle arrest at the
G1/S phase transition, which appeared to virtually eliminate the production of
cytokines. These findings corroborate the temporal, specificity and quantitative
patterns for anti-CD3 immunotoxin administration previously observed in vivo.
PMID- 9640630
TI - Antigen presenting cells and chimerism.
PMID- 9640631
TI - Women's drug use and HIV risk: findings from NIDA's Cooperative Agreement for
Community-Based Outreach/Intervention Research Program.
PMID- 9640632
TI - Women drug users and HIV prevention: overview of findings and research needs.
PMID- 9640633
TI - HIV sex and drug risk behavior and behavior change in a national sample of
injection drug and crack cocaine using women.
AB - This paper describes HIV sex and drug risk behavior and behavior change of
injection drug and crack cocaine using women enrolled in a national multi-site
Cooperative Agreement program. Baseline data on the 1,403 women who were randomly
assigned to a two session intervention that was standardized across sites
indicate that sex and drug risk behavior for becoming infected with HIV was
considerable. Six-month post intervention follow-up data for the same sample of
women show that significant reductions in sex and drug risk behavior were
observed for the entire sample of women for the risk variables under study.
Significant reductions were also demonstrated for various sub-groups of women
enrolled in the study on most of the sex and drug risk variables. Given these
findings, it appears that the standard intervention was effective in assisting
drug using women reduce their behaviors that put them at risk of becoming
infected with HIV. Further research in needed on the development and evaluation
of HIV interventions that target specific risk behaviors and various HIV risk
behavior profiles of women.
PMID- 9640634
TI - Effectiveness of HIV interventions among women drug users.
AB - A prospective cohort study was conducted among chronic injecting and crack
cocaine drug using women. The hypothesis tested was that participation in a
standard-plus-innovative intervention was more likely to produce behavior change
than participation in a standard intervention. Standardized intervention
protocols and corresponding instruments were designed. Data were collected on
drug and sex risk behaviors at baseline and six-month follow-up intervals. The
level of behavioral change in two intervention arms--standard and a standard-plus
innovative intervention--was measured by composite sex risk and drug risk scores
using the generalized estimating equation approach. The results show that on four
risk measures the enhanced intervention was significantly associated with
positive change in both drug use and sexual behavior: less frequent drug use,
less drug use during sex, and more frequent condom use during particular
frequencies for specific types of sexual activities. Public health interventions
are effective when targeting specific risk behaviors through interventions
tailored to prevent HIV and reduce risk behaviors among specific cultural and
gender groups.
PMID- 9640635
TI - AIDS risk perception among women drug users in Hartford, CT.
AB - This paper reports the findings of a study of congruence between AIDS risk
perception and risk behavior in a sample of outreach-recruited out-of-treatment
injection and non-injection crack cocaine using women in Hartford, CT. While
rates of drug- and sex-related AIDS risk were high in this sample, perception of
risk was low among many of the respondents. Variation in risk perception reflects
sociodemographic differences in the sample, with those women who were most
socially isolated exhibiting the greatest incongruence between personal risk and
risk perception. Women who have had contact with health or social service
programs were the most likely to report reductions in risk behavior.
PMID- 9640636
TI - Sex partners of Alaskan drug users: HIV transmission between white men and Alaska
Native women.
AB - This study describes patterns of sexual behavior and condom use in a sample of
1125 Black, White, and Alaska Native drug users. Data are self-reports of recent
sexual behavior, including descriptions of (up to) the five most recent sex
partners. This provided information on 1116 sex partner pairs, of which at least
one partner was a drug user. Sex partner pairs involving a White man and an
Alaska Native woman were frequently reported. Level of condom use within these
pairs was significantly lower than within all other pairs. The implications of a
potential vector of HIV transmission from White, drug using men to Alaska Native
women are discussed.
PMID- 9640637
TI - A comparison of HIV risk behaviors among women drug users from two cities in a
rural state: recommendations for targeted prevention.
AB - Most HIV prevention programs for women target individual risk behaviors while the
influence of larger contextual factors, such as city of residence, are often
neglected. This preliminary study compares women drug users from two different
cities in the largely rural state of Kentucky on HIV risk behaviors. The women
are from Lexington, a medium sized metropolitan area, and from Louisville, a
large metropolitan area. Comparisons between the women from the two cities
indicate that there are many similarities in their risk behaviors, but also some
important differences. The women from Lexington (the smaller city), are more
likely to be at risk for becoming infected with HIV due to their drug use, while
the women from Louisville (the larger city) are more likely to be at risk because
of their sex exchange practices and economic situation. The implications for
prevention are discussed.
PMID- 9640638
TI - Social influences: living arrangements of drug using women at risk for HIV
infection.
AB - The purpose of this study was to explore the associations among living
arrangements, HIV seroprevalence, and HIV risk and protective factors among 1,322
drug users participating in the University of Miami CARES (Community AIDS
Research and Evaluation Studies) HIV intervention program. Living arrangements
may be associated with HIV prevention behaviors; however, these influences can be
either protective or destructive and therefore merit further examination.
Statistical analyses indicated differences in the living arrangements of women
compared with men, and significant associations were noted among women's living
arrangements, HIV seroprevalence, risk behaviors and protective behaviors. The
data from this study suggest that future HIV prevention research should
investigate not only high-risk individuals, but persons with whom they interact
often, especially those with whom they live or with whom they have sex. The next
phase of HIV and drug interventions should be attentive to the incorporation of
social context and social influences, paying particular attention to understudied
populations such as high-risk women.
PMID- 9640639
TI - Differences in condom behaviors and beliefs among female drug users recruited
from two cities.
AB - This paper examines predictors of condom cognitions and condom use for vaginal
sex within women's main and paying partnerships. The sample consisted of active
injection drug and crack-using women recruited from two cities with disparate HIV
rates. A total of 338 drug-using women who reported vaginal sex with a main
and/or paying partner in the prior 30 days were recruited for this study.
Recruitment site was a significant predictor for several of the variables
examined, for both main and paying partners. Ethnicity and prior HIV test result
were also significant predictors, but only for main sex partners. Findings
support previous research and suggest that the factors which predict condom
beliefs, intention, and behaviors are different for main versus paying partners.
Interventions designed to increase condom use must recognize that cognitive
factors associated with condom use may vary by partner type, ethnicity, and
recruitment site, particularly when important contextual variables, such as local
seroprevalence, vary.
PMID- 9640640
TI - Violence and HIV sexual risk behaviors among female sex partners of male drug
users.
AB - OBJECTIVE: Violence and HIV are emerging as interconnected public health hazards
among drug users and their families. The purposes of this study are to (1)
determine the prevalence of sexual and physical abuse of non-drug-using female
sex partners of male drug users, and (2) ascertain the association between such
violence and HIV-related risk behaviors. METHODS: From 11/93 to 11/95, 208 female
sex partners of injection drug or crack users in Collier County, FL, Tucson, AZ,
and Portland, OR, were interviewed as part of a NIDA-funded HIV risk reduction
project. Their mean age was 30 years (range 18-54); 21% were White, 6% African
American, 7% Native American, and 63% Hispanic. RESULTS: Of the 208 women, 28%
reported being sexually molested and 20% raped before age 13; 41% reported being
raped at least once in their lifetime. Forty-two percent of the women were
physically assaulted by their sex partners; 36% had been threatened with
assaulted by their sex partners. Those who were raped or threatened with assault
were more likely to have multiple sex partners and engage in unprotected anal
sex; there was a trend for women who had been physically assaulted to be more
likely to engage in unprotected anal sex. DISCUSSION: Rape, assault and the
threat of assault are commonplace in the histories of female sex partners of male
drug users. Experiences of violence and threats of violence are associated with
heightened risk for the sexual transmission of HIV. Providers of HIV prevention
need to understand the sequelae of violence, and design interventions which
empower women to protect themselves from sexual transmission of HIV.
PMID- 9640641
TI - Urban crack users: gender differences in drug use, HIV risk and health status.
AB - This study assessed gender differences in drug use, HIV risk, and health status
in a sample of urban crack users. Using targeted sampling, 1434 crack users (66%
male and primarily African-American and Puerto Rican), were recruited from the
streets of East Harlem, New York City. A standardized, structured interview was
administered, drug use was validated by urinalysis, and HIV testing was offered.
Gender differences were observed on sociodemographic variables and patterns of
drug use. Other than welfare, men and women cited different major sources of
income. Women reported greater use of crack, and men were more likely to use
injection drugs as well as crack. Data on sexual risk indicated that women had
more sexual partners than men, but the percentage of unprotected vaginal sex for
both men and women was greater for those who did not exchange sex for drugs
and/or money. The number of persons already infected with HIV was substantial.
Many reported histories of other sexually transmitted diseases which were
generally higher among men. Future research should investigate the relationship
between gender and other factors (e.g., ethnicity, geographic location)
associated with HIV risk.
PMID- 9640642
TI - Predictors of HIV infection among women drug users in New York and Miami.
AB - In the US, the number of women diagnosed with AIDS continues to increase. In this
study, women in New York City (East Harlem) and Miami, two sites with high rates
of drug use and HIV infection, were first compared on sociodemographic variables
and risk behaviors. Logistic regression analyses were used to identify
significant, independent predictors of HIV infection in each city. In comparing
women from the two cities, several differences in sociodemographic
characteristics and drug use were observed. In both cities, ever exchanging sex
for drugs and/or money was predictive of HIV infection; and in East Harlem only,
other lifetime risk variables independently predicted HIV infection: drug
injection, having a sexually transmitted disease, and not having graduated from
high school. Results suggest that intervention efforts with women who exchange
sex should be intensified in both cities. Also, further comparisons of women drug
users in AIDS epicenter cities are necessary to provide information on
similarities and differences in sociodemographic characteristics and individual
risk behaviors. More research attention should be focused on examining the social
context of HIV risk in order to develop innovative intervention strategies which
focus on the link between contextual factors and HIV infection.
PMID- 9640643
TI - Streets, drugs, and the economy of sex in the age of AIDS.
AB - Drug addicted women whose economic and social base is urban streets face limited
options for income generation and multiple dangers of predation, assault, arrest,
and illness. Exchanging sex for money or drugs offers one important source of
income in this context. Yet the legal, social, and safety risks associated with
these exchanges reduce the likelihood of regular safer sex practices during these
encounters, thereby increasing the risk of HIV infection. Such conditions lead
women engaged in sexual exchanges for money to varied and complex responses
influenced by multiple and often contradictory pressures, both personal and
contextual. Street-recruited women drug users in an AIDS prevention program in
Hart-ford, Connecticut reported a range of condom use when engaging in sex for
money exchanges. This paper explores their differences by ethnicity, economic
resources, and drug use, and analyzes these and other factors that impact on
street risks through sexual income generation. Surveys and in-depth interviews
with drug-addicted women sex workers describe their various approaches to
addressing multiple risks on the streets and suggest significant effort by women
in these contexts to avoid the many risks, including HIV infection.
PMID- 9640644
TI - ATP-binding-cassette (ABC) transport systems: functional and structural aspects
of the ATP-hydrolyzing subunits/domains.
AB - Members of the superfamily of adenosine triphosphate (ATP)-binding-cassette (ABC)
transport systems couple the hydrolysis of ATP to the translocation of solutes
across a biological membrane. Recognized by their common modular organization and
two sequence motifs that constitute a nucleotide binding fold, ABC transporters
are widespread among all living organisms. They accomplish not only the uptake of
nutrients in bacteria but are involved in diverse processes, such as signal
transduction, protein secretion, drug and antibiotic resistance, antigen
presentation, bacterial pathogenesis and sporulation. Moreover, some human
inheritable diseases, like cystic fibrosis, adrenoleukodystrophy and Stargardt's
disease are caused by defective ABC transport systems. Thus, albeit of major
significance, details of the molecular mechanism by which these systems exert
their functions are still poorly understood. In this review, recent data
concerning the properties and putative role of the ATP-hydrolyzing
subunits/domains are summarized and compared between bacterial and eukaryotic
systems.
PMID- 9640645
TI - Physiology of organic nitrogen acquisition by ectomycorrhizal fungi and
ectomycorrhizas.
AB - Ectomycorrhizal fungi are symbiotically associated microorganisms which
ecological importance has been repeatedly demonstrated. There has been a
considerable amount of research aimed at assessing the ability of ectomycorrhizal
fungi and ectomycorrhizas to utilize organic nitrogen sources. The fate of soil
proteins, peptides and amino acids has been studied from a number of
perspectives. Exocellular hydrolytic enzymes have been detected and characterized
in a number of ectomycorrhizal and ericoid fungi. Studies on amino acid transport
through the plasma membrane have demonstrated the ability of ectomycorrhizal
fungi to take up the products of proteolytic activities. Investigations on
intracellular metabolism of amino acids have allowed the identification of the
metabolic pathways involved. Possible intracellular compartmentation of amino
acids will be examined by immunocytochemistry. Further translocation of amino
acids in symbiotic tissues has been established by experiments using isotopic
tracers, although the exact nature of the nitrogenous compounds transferred at
the symbiotic interface remained unclear. One of the main future challenges in
the physiology of organic nitrogen acquisition is to determine the nature, the
regulation and the location of N-compound transporters at the soil-fungus and
fungus-plant interfaces. The molecular approach which is just emerging in this
particular research area will greatly improve our knowledge. Future research
should also address the extent of competition between different ectomycorrhizal
species and between different microbial populations for organic nitrogen.
PMID- 9640646
TI - Adhesin-receptor interactions in Pasteurellaceae.
AB - The ability of bacteria to adhere to mucosal epithelium is dependent on the
expression of adhesive molecules or structures, called adhesins, that allow
attachment of the organisms to complementary molecules on mucosal surfaces, the
receptors. Important human and animal pathogens are found among the
Pasteurellaceae family which includes Haemophilus, Actinobacillus, and
Pasteurella organisms. The purpose of this paper is to review the adhesin
receptor systems found in Pasteurellaceae, with an emphasis on recent
developments in this specific area. Most of these organisms can employ multiple
molecular mechanisms of adherence (or multiple adhesins) to initiate infection.
Indeed, a wide variety of adhesins are expressed by members of the
Pasteurellaceae, and different proteins (e.g. fimbriae, fibrils, outer membrane
proteins) as well as polysaccharides (lipooligosaccharides, lipopolysaccharides,
capsular polysaccharides) were clearly shown to play an important role in
adherence. In many instances, these adhesins have proved to represent good
vaccine candidates. Surprisingly, the receptors on host mucosal surfaces have yet
been identified in very few cases.
PMID- 9640647
TI - Habitat islands, genetic diversity, and gene flow in a Patagonian rodent.
AB - The effects of terrestrial habitat islands on gene flow and genetic diversity in
animal populations have been predicted and discussed in theoretical terms, but
empirical data are needed to test these predictions and provide an understanding
of the relationships of life-history characteristics to genetics of insular
species. We studied saxicolous mice (Phyllotis xanthopygus) in Patagonia to
explore genetic structure, phylogeography, and gene flow in a species inhabiting
natural habitat islands. Phylogeographic analyses based on mtDNA sequences
revealed two haplotype clades, which presumably reflect early Pleistocene factors
that temporarily separated the mice into two geographically isolated groups. The
Rio Chubut, which lies within a glacial drainage basin bisecting northern
Patagonia, might have affected gene flow in the species. Although we anticipated
isolation by distance and founder phenomena associated with habitat islands, in
some habitat patches we found evidence of high local genetic diversity. The
amount of divergence in the mitochondrial cytochrome b gene (approximately 3.4%)
in animals at a single locality could best be explained through a combination of
historical factors and metapopulation source-sink theory. Demographic shifts,
dispersal, and episodic recolonization are important in the life history and
genetic population structure of P. xanthopygus.
PMID- 9640648
TI - Molecular population genetics of the red kangaroo (Macropus rufus): mtDNA
variation.
AB - The genetic population structure of a large, wide-ranging marsupial, the red
kangaroo (Macropus rufus) was assessed using sequence and haplotype frequency
data of mitochondrial DNA (mtDNA) from locations across the species range in
Australia. Results from sequence data revealed extensive haplotype diversity
within the red kangaroo (32/34 sequences were unique). Sequence diversity was
distributed within rather than between geographical regions across the species
range. Genetic connectivity across the range of the species has therefore been
maintained over the long term. On a smaller within-region scale, significant
genetic structuring was evident from heterogeneity of haplotype frequencies
amongst sampling sites. The geographical scale of panmictic populations differed
across the continent with more restricted genetic populations occurring in areas
with greater topographic and habitat complexity. We propose that these
differences in area of genetic populations are the result of population responses
to limiting ecological factors during drought.
PMID- 9640649
TI - Molecular genetic identification of southern hemisphere beaked whales (Cetacea:
Ziphiidae).
AB - To assist in the species-level identification of stranded and hunted beaked
whales, we compiled a database of 'reference' sequences from the mitochondrial
DNA control region for 15 of the 20 described ziphiid species. Reference samples
for eight species were obtained from stranded animals in New Zealand and South
Australia. Sequences for a further seven species were obtained from a previously
published report. This database was used to identify 20 'test' samples obtained
from incompletely documented strandings around New Zealand. Analyses showed that
four of these 'test' specimens (20%) had initially been misidentified. These
included two animals of particular interest: (i) a Blainville's beaked whale
(Mesoplodon densirostris), the first record of this species in New Zealand
waters; and, (ii) a juvenile Andrews' beaked whale (Mesoplodon bowdoini), a
species known from just over 20 strandings worldwide. A published sequence from a
beaked whale product purchased in the Republic of Korea was identified as a
Cuvier's beaked whale (Ziphius cavirostris). Levels of intra- and interspecific
variation were compared to determine the potential for misidentification when the
database or taxonomy is incomplete. Intraspecific variation was generally < 2%,
and interspecific divergence was generally > 4.7%. Exceptions were within-species
variation in Hyperoodon planifrons, southern bottlenosed whale (4.12%), which
exceeded the variation between the two species of Berardius (3.78%), and
variation between the two specimens assigned to M. hectori, Hector's beaked whale
(7.14%). The latter case appears to be an error in species identification, and
could represent the discovery of a new species of beaked whale.
PMID- 9640650
TI - Population structure of nuclear and mitochondrial DNA variation among humpback
whales in the North Pacific.
AB - The population structure of variation in a nuclear actin intron and the control
region of mitochondrial DNA is described for humpback whales from eight regions
in the North Pacific Ocean: central California, Baja Peninsula, nearshore Mexico
(Bahia Banderas), offshore Mexico (Socorro Island), southeastern Alaska, central
Alaska (Prince Williams Sound), Hawaii and Japan (Ogasawara Islands). Primary
mtDNA haplotypes and intron alleles were identified using selected restriction
fragment length polymorphisms of target sequences amplified by the polymerase
chain reaction (PCR-RFLP). There was little evidence of heterogeneity in the
frequencies of mtDNA haplotypes or actin intron alleles due to the year or sex
composition of the sample. However, frequencies of four mtDNA haplotypes showed
marked regional differences in their distributions (phi ST = 0.277; P < 0.001; n
= 205 individuals) while the two alleles showed significant, but less marked,
regional differences (phi ST = 0.033; P < 0.013; n = 400 chromosomes). An
hierarchical analysis of variance in frequencies of haplotypes and alleles
supported the grouping of six regions into a central and eastern stock with
further partitioning of variance among regions within stocks for haplotypes but
not for alleles. Based on available genetic and demographic evidence, the
southeastern Alaska and central California feeding grounds were selected for
additional analyses of nuclear differentiation using allelic variation at four
microsatellite loci. All four loci showed significant differences in allele
frequencies (overall FST = 0.043; P < 0.001; average n = 139 chromosomes per
locus), indicating at least partial reproductive isolation between the two
regions as well as the segregation of mtDNA lineages. Although the two feeding
grounds were not panmictic for nuclear or mitochondrial loci, estimates of long
term migration rates suggested that male-mediated gene flow was several-fold
greater than female gene flow. These results include and extend the range and
sample size of previously published work, providing additional evidence for the
significance of genetic management units within oceanic populations of humpback
whales.
PMID- 9640654
TI - Microsatellite loci for stringless bees.
PMID- 9640655
TI - Characterization of coastal cutthroat trout (Oncorhynchus clarki clarki)
microsatellites and their conservation in other salmonids.
PMID- 9640656
TI - Broader context, global outlook.
PMID- 9640657
TI - Sending a message.
PMID- 9640658
TI - Steeling ourselves against cardiac arrest.
PMID- 9640659
TI - Have you heard?
PMID- 9640660
TI - Effects of (+)-8',8',8'-trifluoroabscisic acid on alpha-amylase expression and
sugar accumulation in rice cells.
AB - The effects of (+)-8',8',8'-trifluoroabscisic acid (trifluoro-ABA) on alpha
amylase expression were studied in rice embryoless half-seeds, scutella, and
suspension-cultured cells derived from the embryo, and the effects of the analog
on sugar accumulation were also studied in scutella and suspension-cultured
cells. Treatment with (+)-trifluoro-ABA strongly inhibited the gibberellic acid
inducible expression of alpha-amylase I-1 encoded by RAmy1A in the aleurone
layers of embryoless half-seeds at the levels of transcription, protein
synthesis, and enzyme activity. It was also found that (+)-trifluoro-ABA
stimulated (i) the uptake of glucose from the incubation medium and (ii) the
synthesis of sucrose in scutellar tissues and suspension-cultured cells of rice.
The biological activity of (+)-trifluoro-ABA was found to be more potent and
persistent than that of natural ABA. We further examined the effects of trifluoro
ABA on the expression of alpha-amylase I-1 in scutellar tissues and suspension
cultured cells. It was found that (+)-trifluoro-ABA did not inhibit the formation
of alpha-amylase I-1 in the absence of external glucose. However, glucose and (+)
trifluoro-ABA cooperatively suppressed the formation of alpha-amylase I-1.
Judging from these results, we conclude that the regulatory mechanism for the
expression of alpha-amylase I-1 in the scutellar epithelium is distinguishable
from that operating in the aleurone layer.
PMID- 9640661
TI - In rice, Oryzalin and abscisic acid differentially affect tubulin mRNA and
protein levels.
AB - The effect of the anti-microtubular drug Oryzalin (3,5-dinitro-N4,N4
dipropylsulfanilamide) on growth and elongation of rice (Oryza sativa L. cv.
Arborio) roots and coleoptiles was investigated. At 100 nM, Oryzalin strongly
reduced primary root elongation, caused loss of cell anisotropy and the
disappearance of the cortical microtubule array. Under these conditions the
amounts of alpha- and beta-tubulin protein, but not mRNA, were heavily reduced.
Similar data were also obtained in coleoptile segments treated with different
concentrations of Oryzalin. However, when coleoptile elongation was inhibited by
cis-abscisic acid, remarkable decreases in alpha- and beta-tubulin accumulation
were observed to occur at the mRNA level but not at the protein level. The
transcriptional decreases could be reversed by re-addition of 3-indole acetic
acid. Altogether, these data indicate that rice tubulin accumulation can be
controlled at different levels, mRNA or protein, in response to Oryzalin or
abscisic acid treatments.
PMID- 9640662
TI - Gravitropism and gravimorphism during regeneration from protoplasts of the moss
Ceratodon purpureus (Hedw.) Brid.
AB - Wild-type (WT) protonemata of the moss Ceratodon purpureus grow upwards in
darkness (negative gravitropism), whereas protonemata of the mutant, wrong-way
response (wwr-1) grow down. Since Ceratodon protoplasts regenerate to form new
protonemata, we analyzed whether the direction of filament emergence was
influenced by gravity (gravimorphism) and determined the cytological events that
correlated with the onset of gravitropism in WT and wwr-1 filaments formed de
novo. In the WT the direction of filament emergence appeared to be gravimorphic
as more than 66% of the new filaments emerged above the horizontal. In contrast,
the direction of filament emergence was random in wwr-1. Tip-growing cells of
both genotypes became gravitropic within a total of one to two cell divisions.
Gravitropic curvature in wwr-1 was opposite in direction to that of WT, and the
timing of curvature was comparable, indicating that the wwr-1 mutation acts
during the onset of gravitropic competence. In time-lapse studies of both
genotypes, neither a plastid-free zone nor obvious and extensive plastid
sedimentation characteristic of mature dark-grown protonemata was observed in the
new filaments prior to gravitropic curvature. Thus, it appears that these latter
two features are not required for gravitropism in new protonemal filaments from
protoplasts.
PMID- 9640663
TI - Purification of ornithine carbamoyltransferase from kidney bean (Phaseolus
vulgaris L.) leaves and comparison of the properties of the enzyme from
canavanine-containing and -deficient plants.
AB - Kidney bean (Phaseolus vulgaris L.) ornithine carbamoyltransferase (OCT; EC
2.1.3.3) was purified to homogeneity from leaf homogenates in a single-step
procedure, using delta-N-(phosphonoacetyl)-L-ornithine-Sepharose 6B affinity
chromatography. The 8540-fold-purified OCT exhibited a specific activity of 526
micromoles citrulline per minute per milligram of protein at 35 degrees C and pH
8.0. The enzyme represents approximately 0.01% of the total soluble protein in
the leaf. The molecular mass of the native enzyme was approximately 109 kDa as
estimated by Sephacryl S-200 gel filtration chromatography. The purified protein
ran as a single band of molecular mass 36 kDa when subjected to sodium dodecyl
sulfate-polyacrylamide gel electrophoresis and at a single isoelectric point of
6.6 when subjected to denaturing isoelectric focusing. These results suggest that
the enzyme is a trimer of identical subunits. Among the tested amino acids, L
cysteine and S-carbamoyl-L-cysteine were the most effective inhibitors of the
enzyme. The OCT of kidney bean showed a very low activity towards canaline. The
OCTs of canavanine-deficient plants have very low canaline-dependent activities,
but the OCTs of canavanine-containing plants showed high canaline-dependent
activities. It was assumed that the substrate specificity of this enzyme
determines the canavanine synthetic activity of the urea cycle.
PMID- 9640664
TI - Membrane fractionation and enrichment of callose synthase from pollen tubes of
Nicotiana alata Link et Otto.
AB - The callose synthase (UDP-glucose: 1,3-beta-D-glucan 3-beta-D-glucosyl
transferase; EC 2.4.1.34) enzyme (CalS) from pollen tubes of Nicotiana alata Link
et Otto is responsible for developmentally regulated deposition of the cell wall
polysaccharide callose. Membrane preparations from N. alata pollen tubes grown in
liquid culture were fractionated by density-gradient centrifugation. The CalS
activity sedimented to the denser regions of the gradient, approximately 1.18
g.ml-1, away from markers for Golgi, endoplasmic reticulum and mitochondria, and
into fractions enriched in ATPase activity and in membranes staining with
phosphotungstic acid at low pH. This suggests that pollen-tube CalS is localised
in the plasma membrane. Callose synthase activity from membranes enriched by
downward centrifugation was solubilised with digitonin, which gave a 3- to 4-fold
increase in enzyme activity, and the solubilised activity was then enriched a
further 10-fold by product entrapment. The complete procedure gave final CalS
specific activities up to 1000-fold higher than those of pollen-tube homogenates.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that several
polypeptides co-fractionated with CalS activity through purification, with a
polypeptide of 190 kDa being enriched in product-entrapment pellets.
PMID- 9640665
TI - 4-Hydroxybenzoate 3-geranyltransferase from Lithospermum erythrorhizon:
purification of a plant membrane-bound prenyltransferase.
AB - Geranyldiphosphate:4-hydroxybenzoate 3-geranyltransferase is a regulatory enzyme
in the biosynthesis of shikonin, a phytoalexin and pharmaceutical produced by
cell cultures of Lithospermum erythrorhizon Sieb. et Zucc. In Linsmaier-Skoog
medium, the activity of this enzyme could be enhanced more than 200-fold by
addition of methyl jasmonate, and this culture material was used for the
solubilization and purification of the enzyme. Of various detergents examined,
digitonin was the most suitable for the solubilization of the enzyme. The
solubilized enzyme was purified 800-fold by chromatography over diethylaminoethyl
(DEAE)-Sephacel, Heparin-Sepharose, Reactive Green 19-Agarose, and Cholic Acid
Agarose. The purified enzyme required magnesium ions as cofactor and was highly
specific for geranyldiphosphate (GPP) and 4-hydroxybenzoate (4HB) as substrates.
The K(m) values for 4HB and GPP were calculated by the method of Lineweaver and
Burk as 18.4 microM and 13.8 microM, respectively.
PMID- 9640666
TI - Effects of over-expression of strictosidine synthase and tryptophan decarboxylase
on alkaloid production by cell cultures of Catharanthus roseus.
AB - Cells of Catharanthus roseus (L.) G. Don were genetically engineered to over
express the enzymes strictosidine synthase (STR; EC 4.3.3.2) and tryptophan
decarboxylase (TDC; EC 4.1.1.28), which catalyze key steps in the biosynthesis of
terpenoid indole alkaloids (TIAs). The cultures established after Agrobacterium
mediated transformation showed wide phenotypic diversity, reflecting the
complexity of the biosynthetic pathway. Cultures transgenic for Str consistently
showed tenfold higher STR activity than wild-type cultures, which favored
biosynthetic activity through the pathway. Two such lines accumulated over 200
mg.L-1 of the glucoalkaloid strictosidine and/or strictosidine-derived TIAs,
including ajmalicine, catharanthine, serpentine, and tabersonine, while
maintaining wild-type levels of TDC activity. Alkaloid accumulation by highly
productive transgenic lines showed considerable instability and was strongly
influenced by culture conditions, such as the hormonal composition of the medium
and the availability of precursors. High transgene-encoded TDC activity was not
only unnecessary for increased productivity, but also detrimental to the normal
growth of the cultures. In contrast, high STR activity was tolerated by the
cultures and appeared to be necessary, albeit not sufficient, to sustain high
rates of alkaloid biosynthesis. We conclude that constitutive over-expression of
Str is highly desirable for increased TIA production. However, given its
complexity, limited intervention in the TIA pathway will yield positive results
only in the presence of a favorable epigenetic environment.
PMID- 9640667
TI - Lysine-rich gamma-zeins are secreted in transgenic Arabidopsis plants.
AB - We have previously shown that the maize (Zea mays L.) storage prolamine gamma
zein, accumulates in endoplasmic reticulum-derived protein bodies in transgenic
plants of Arabidopsis thaliana (L.) ecotype R + P. The retention of gamma-zein in
the endoplasmic reticulum was found to be mediated by structural features
contained in the polypeptide, an N-terminal proline-rich and a C-terminal
cysteine-rich domain which were necessary for the correct retention and assembly
of gamma-zein within protein bodies (M.I. Geli et al., 1994, Plant Cell 6: 1911
1922). In the present work we incorporated in the gamma-zein gene lysine-rich
coding sequences which were positioned after the N-terminal proline-rich domain
and at five amino-acid residues from the C-terminus. The targeting of lysine-rich
gamma-zeins was analyzed by expression of chimeric genes regulated by the
cauliflower mosaic virus (CaMV) 35S promoter in transgenic Arabidopsis plants.
The lysine-rich gamma-zeins were detected by immunoblotting and we found that
these proteins were modified posttranslationally to reach their mature form.
Subcellular fractionation and immunocytochemical studies demonstrated that
glycosylated lysine-rich gamma-zeins were secreted to the cell wall of transgenic
Arabidopsis leaf cells.
PMID- 9640668
TI - Overexpression of pyrophosphatase leads to increased sucrose degradation and
starch synthesis, increased activities of enzymes for sucrose-starch
interconversions, and increased levels of nucleotides in growing potato tubers.
AB - Overexpression of inorganic pyrophosphatase (PPase) from Escherichia coli in the
cytosol of plants (ppa 1 plants) leads to a decrease of inorganic pyrophosphate
(PPi; U. Sonnewald, 1992, Plant J 2: 571-581). The consequences for sucrose
starch interconversions have now been studied in growing potato (Solanum
tuberosum L. cv. Desiree) tubers. Sucrose is degraded via sucrose synthase and
UDP-glucose pyrophosphorylase in growing tubers, and it was expected that the low
PPi in the ppa 1 transformants would restrict the mobilisation of sucrose and
conversion to starch. Over-expression of PPase resulted in an accumulation of
sucrose and UDP-glucose, and decreased concentrations of hexose phosphates and
glycerate-3-phosphate in growing ppa 1 tubers. Unexpectedly, the rate of
degradation of [14C] sucrose was increased by up to 30%, the rate of starch
synthesis was increased, and the starch content was increased by 20-30% in ppa 1
tubers compared to wild-type tubers. Reasons for this unexpectedly efficient
conversion of sucrose to starch in the ppa 1 tubers were investigated. (i) The
transformed tubers contained increased activities of several enzymes required for
sucrose-starch interconversions including two- to three-fold more sucrose
synthase and 60% more ADP-glucose pyrophosphorylase. They also contained 30-100%
increased activities of several glycolytic enzymes and amylase, increased
protein, and unaltered or slightly decreased starch phosphorylase, acid invertase
and mannosidase. (ii) The transformants contained higher pools of uridine
nucleotides. As a result, although the UDP-glucose pool is increased two- to
threefold, this does not lead to a decrease of UTP or UDP. (iii) The
transformants contained twofold larger pools of ATP and ADP, and ADP-glucose was
increased by up to threefold. In stored ppa 1 tubers, there were no changes in
the activities of glycolytic enzymes, and nucleotides did not increase. It is
concluded that in growing tubers PPi has a wider-significance than just being an
energy donor for specific reactions in the cytosol. Increased rates of PPi
hydrolysis also affect general aspects of cell activity including the levels of
nucleotides and protein. Possible ways in which PPi hydrolysis could affect these
processes are discussed.
PMID- 9640669
TI - Tissue-related changes in methyl-esterification of pectic polysaccharides in
cauliflower (Brassica oleracea L. var. botrytis) stems.
AB - Pectic substances are a major component of cell walls in vegetable plants and
have an important influence on plant food texture. Cauliflower (Brassica oleracea
L. var. botrytis) stem sections at different regions of the mature plant stem
have been monitored for tissue-related changes in the native pectic
polysaccharides. Chemical analysis detected appreciable differences in the degree
of methyl-esterification (ME) of pectic polysaccharides. About 65% of
galacturonic acid (GalpA) residues were methyl-esterified in floret tissues.
Relative ME showed a basipetal decrease, from 94% in the upper stem to 51% in the
lower-stem vascular tissues. The decrease was not related to a basipetal increase
in glucuronic acid (GlcpA) residues. The monoclonal antibodies, JIM 5 and JIM 7,
produced distinct labelling patterns for the relatively low-methylesterified and
high-methyl-esterified pectin epitopes, respectively. Labelling was related to
cell type and tissue location in the stem. Floret cell walls contained epitopes
for both JIM 5 and JIM 7 throughout the wall. Stem vascular tissues labelled more
strongly with JIM 5. Whereas pith parenchyma in the upper stem labelled more
strongly with JIM 7, in the lower-stem pith parenchyma, JIM 5 labelling
predominated. Localization of pectic polysaccharide epitopes in cell walls
provides an insight into how structural modifications might relate to the
textural and nutritional properties of cell walls.
PMID- 9640670
TI - Cardenolide 16'-O-glucohydrolase from Digitalis lanata. Purification and
characterization.
AB - A three-step chromatographic procedure was developed for purification of
cardenolide 16'-O-glucohydrolase (CGH) from Digitalis lanata Ehrh. leaves,
including Phenyl-Sepharose hydrophobic interaction chromatography followed by SP
Sepharose cation exchange and Q-Sepharose anion-exchange chromatography. Starting
with acetone dry powder the purification resulted in an 760-fold enrichment of
CGH. Molecular weight, substrate specificity, pH optimum and temperature
stability of CGH were determined. Antibodies against CGH were prepared in
rabbits. The SDS gel electrophoresis of protein extracts from leaves of D. lanata
and other D. species showed bands at 70 kDa and 36 kDa reacting with the
antibodies. The 70-kDa protein is the main protein stained with CGH antibodies in
freshly prepared extracts of D. lanata. It may represent undegraded CGH. The 36
kDa protein is enriched in aged CGH preparations. It is probably a degradation
product. Proteins related to 70-kDa and 36-kDa bands also occur in crude protein
preparations from leaves of D. heywoodii P. et M. Silva, D. mariana Boiss., D.
purpurea L., and D. thapsi L. indicating that CGH is also present in these
species. Purified CGH was digested with proteases V8 and Lys-C and the resulting
fragments obtained were sequenced. One fragment had the typical amino-acid
sequence of the catalytic center of family-1 glycosyl hydrolases (EC 3.2.1.x).
Cardenolide 16'-O-glucohydrolase, like the other members of this enzyme family,
appeared to have a glutamic acid residue directly involved in glycosidic bond
cleavage as a nucleophile.
PMID- 9640671
TI - [Ethics in scientific research].
PMID- 9640672
TI - Growth and differentiation of adult Mongolian gerbil epidermal cells in culture.
AB - A simple protocol for the growth and differentiation of adult Mongolian gerbil
epidermal cells is reported. Insulin (8 micrograms/ml) and reduced levels of
serum supplementation (2%) were sufficient for the maintenance of these cells in
culture. Primary cultures were maintained as a proliferative monolayer in a
medium with low calcium concentration (< 0.3 mM). Terminal differentiation of
cultures was induced by raising the calcium concentration (1.6 mM) in the medium.
These results support the concept derived from mouse epidermal cell culture that
calcium is an important regulator of mammalian epidermal cell growth and
differentiation. The present protocol also represents a useful tool for studies
of mechanisms involved in epidermal cell growth and differentiation in a
laboratory animal.
PMID- 9640673
TI - Adult gerbil epidermal cells resistant to terminal differentiation associated
with initiation of carcinogenesis.
AB - In order to identify the cellular basis of the gerbil skin unresponsiveness to
two-stage carcinogenesis, it was studied the effect of an initiating dose of
carcinogen on the biological behaviour of gerbil skin. Treatment of adult gerbil
epidermal cells either in vivo or in vitro with 3-methylcholanthrene yielded
cells which were resistant to terminal differentiation induced by calcium. These
results support the concept derived from the mouse model system of skin
carcinogenesis in which initiation is associated with an altered program of
epidermal differentiation. The results also suggest that relative resistance of
gerbil skin to two-stage carcinogenesis is related to promotion stage.
PMID- 9640674
TI - [Cyclic nucleotide phosphodiesterases: diversity, classification, structure and
function].
AB - During the last years there have been major advances in the knowledge of cyclic
nucleotide phosphodiesterases. Particularly, referred to the presence of multiple
different isozymes. Seven different phosphodiesterase gene families, have been
described in mammalian tissues, containing several distinct genes, most of them
expressed in different tissues as functionally unique splice variants. This
article includes various aspects of the currently accepted nomenclature,
structure and function of each family of phosphodiesterases. Finally, a brief
discussion of the presence and role of these enzymes in the cell proliferation
and differentiation processes, in parasites of the Trypanosmatidae family, is
provided.
PMID- 9640675
TI - [Genetic structure of the population of Guarico, Venezuela, studied through
isonymy].
AB - The genetic structure of the State of Guarico, Venezuela, was studied through the
distribution of surnames from individuals above 40 years of age, obtained from
the register of electors. The sample studied consisted in 109,200 individuals and
14,138 different surnames. For each of the 32 counties of the State, the
following estimators were calculated: percentage of the population included in
surnames which appear only once (estimator A), percentage of the population
included in the seven most frequent surnames (estimator B), the coefficient of
consanguinity due to random isonymy (n phi ii), and Karlin and McGregors ni nu,
an estimator of migration. The correlation between n phi ii and B was 0.97,
indicating that 94% of the variation observed in the coefficient of consanguinity
due to random isonymy is due to the seven most frequent surnames. The correlation
between A and ni was 0.93, so that 86% of the variation observed in ni, is due to
surnames which appear only once. On the other hand, correlations between A and B,
and between n phi ii and nu were non significant (0.25 and 0.01 respectively),
meaning that they are measuring different features of population structure: B and
n phi ii, and v were non significant (0.25 and 0.01 respectively), meaning that
they are measuring different features of population structure: B and n phi ii,
isolation, and A and nu, migration. The most isolated counties of Guarico,
according to n phi ii and B, are Santa Rita, Espino, El Calvario, Ortiz and Santa
Maria de Ipire. Microdifferentiation of the State was studied through the
estimation of RST, which gave a value of 0.0008. Comparing this value with those
obtained in other Venezuelan States, it is found that Guarico, with Aragua and
Yaracuy, are among the least differentiated States, probably because of the
absence of important geographical barriers and the nearness to the Capital City
of our country.
PMID- 9640676
TI - [The canarians of San Antonio de los altos, Edo, Miranda, Venezuela. Isolation
and marriage unions between 1900 at 1981].
AB - We present results of a study on isolation and endogamy in San Antonio de Los
Altos a Venezuelan town founded in 1683 by 41 Spanish families of Canarian
origin. The study was done with the civil marital records registered during the
years 1905 to 1981. The results show that the same few surnames cover an
important proportion of individuals in all the periods studied, which suggests
that these belong to the traditional families. An important endogamy is revealed
through the frequencies of surnames, birth places of spouses, and the isonymy
analysis, which decrease after 1960 with the rupture of the isolate. The higher
Fn values and the predominance of some types of isonymy suggests the existence of
preferential unions. Geographic isolation and some economic factors, such as the
property of the land, could have favoured the isonymy and endogamy observed among
surnames of the founders of the town.
PMID- 9640677
TI - Foodborne intestinal parasitic protozooses.
PMID- 9640678
TI - [Vegetables for human consumption as probable source of Toxocara sp. infection in
man].
AB - Although Toxocara canis life cycle is known, other possible mechanisms
dynamically involved in its transmission to man are still ignored. The object of
the present investigation was to search the occurrence of Toxocara sp. eggs in
vegetables which humans consume. Five hundred and thirty six vegetables from a
supply distribution center in Mexico City (Distrito Federal) were examined. Those
included 212 carrots, 76 potatoes, 31 radishes, 22 mushrooms, 27 lettuces, 20
sweet potatoes and 66 bundles of spinaches, 32 bundles of salt-worts, 29 bundles
of coriander, and 21 bundles of purslane. Each unit or bundle was washed with 50
ml of sterilized water, allowing sedimentation at room temperature for 8 hours.
Five ml of sediment were centrifugated at 3,000 r.p.m. for 5 minutes. Sediment
was examined in lugol stained fresh plates through light microscopy, which turned
to be Toxocara sp. eggs were found only in two vegetables: 1.9% of carrots and
6.5% of radishes. Toxocara sp. eggs were: 66.7% recently emitted and 33.3%
embryonated. Other parasite elements were: Ascaris lumbricoides eggs 1.9% in
carrots, 2.6% in potatoes, 9.1% in mushrooms, 6.9% in corianders, 20.0% in sweet
potatoes and 6.1% in spinachs. Entamoeba histolytica cyts were found in 0.9% of
carrots. Soil contamination with Toxocara sp. eggs from parasitized dogs or cats,
or with either sewage systems or contaminated water where vegetables for human
consumption are grown, play a role as a transmission mechanism must be deeperly
studied since 33.3% of Toxocara sp. eggs found contained larvae, potentially
infective to man.
PMID- 9640679
TI - [Cryptosporidiosis in children with acute diarrhea from Ciego de Avila province,
Cuba].
AB - An epidemiological and clinical study of criptosporidiosis in children from Ciego
de Avila province was carried out from 1987 to 1994. During this period 14,895
children with acute diarrhea were studied. Cryptosporidium sp. oocysts were found
in the feces of 1,256 (8.4%) of them. Isolated cases prevailed over outbreaks,
being the incidence rate proportional in both urban and rural areas. Seventy nine
point seven per cent of infected children were less one year old, predominating
the age group 6-11 months old. No influence of seasons on the occurrence of the
parasitose was observed. The most frequently detected symptoms and signs were
diarrhea, vomits and loss of weight. The main epidemiological factors were: 81.0%
of ill children drank water directly from the aqueduct, 12.8% lived in
overcrowded conditions, 11.0% had animals and 10.7% attended nursery schools.
PMID- 9640680
TI - [Immunodiagnosis in 647 suspected clinical cases of toxoplasmosis].
AB - Though Toxoplasma gondii can cause severe pathology in human, in most of the
cases it produces only asymptomatic infection. So, it is important to dispose
some methods capables to discriminate between acute and chronic infections. An
indirect hemagglutination test (IHAT), dye test (DT) and complement fixation test
(CFT) were performed in 647 sera from patients suspected of having toxoplasmosis
infection. IHAT and DT titer > or = 4 and CFT > or = 5 were considered positive.
Titers were classified as follows: low (4-16), median (64-512) and high (> or =
1000) for IHAT and DT. The pathologies for demanding these serological tests
were: adenopathies (58), nephropathies (72), neuropathies (30), obstetrical
problems (65), opthalmopathies (147), AIDS (237) and miscellaneous (37). Global
positivity of 49.5% and 4.5% for IHAT/DT and CFT respectively were found. The
positivity for the different groups were: adenopathies (48.3% and 13.8%),
nephropathies (43.1% and 1.4%), neuropathies (26.7% and 3.3%), obstetrical
problems (40.0% and 0.0%), ophthalmopathies (59.9% and 8.2%), AIDS (52.1% and
2.5%) and miscellaneous (40.5% and 2.7%) for IHAT/DT and CFT respectively. Low
and median titers for IHAT/DT were found in 81.3% of cases. A high agreement in
frequency of concordant and discordant titers of IHAT/DT and CFT, indicating a
recent or acute infection was observed. This fact was more relevant in
adenopathies, ophthalmopathies (uveitis) and AIDS groups.
PMID- 9640682
TI - [Spirocamallanus hilarii (Nematoda, Camallanidae) fresh water fishes parasite
from the dam of Termas de Rio Hondo, Santiago del Estero, Argentina].
AB - Spirocamallanus hilarii (Nematoda, Camallanidae) is cited parasitizing five fresh
water fish species: Salminus maxillosus Leporinus obtusidens, Hoplias malabaricus
malabaricus, Oligosarcus jenynsii and Pimelodus albicans, captured in Termas de
Rio Hondo pond, province of Santiago del Estero, Argentina. Morphologic and
morphometric parasitological studies were done. The specimens described were
drawned and photographed. In addition, the following parasitic infection indexes
were calculated: Prevalence 26.5%, Mean 6.6 and Maximum Intensity 27.
PMID- 9640681
TI - [Cercaria chaetotaxy of 2 Venezuelan strains of Schistosoma mansoni].
AB - By means of the silver impregnation of two lots of Schistosoma mansoni cercariae
belonging to the strains: JR (32 cercariae) and C5 (45 cercariae), the number and
pattern of disposition of the argentophillic papillae were determined with the
following results: Average number of total dorsal papillae: 12.1 (JR strain) and
12.0 (C5 strain); the variation coefficients in this surface were less than 4%
(JR strain) and bigger in JR than C5 strain. Average number of total ventral
papillae: 12.15 (JR), 11.97 (C5); maximum value of the variation coefficient:
6.4% (JR), higher in JR than C5 strain. When the ventral surface was classified
in four quadrants, the average number of papillae by quadrant was: quadrant A:
1.15 (JR) and 1.06 (C5): B: 1.06 (JR) and 1 (C5); C: 4.97 (JR) and 4.96 (C5); D:
5.03 (JR) and 4.98 (C5). The variation coefficients were higher in the A and B
ventral quadrants, reaching maximum values of 31.9%, and 61.0% for the posterior
quadrants C and D. When the ventral surface was divided in three equal parts for
determining the position of the most variable papillae of this area, the greatest
value of the variation coefficients obtained were for the 2nd thirds of the
cercariae: 89.8% and 76.8% for C5 strain and 43.5% and 56.8% for JR strain. In
relation to the total lateral papillae, the average numbers were: 17.0 (JR) and
16.6 (C5), with a maximum value of variation coefficient of (8.1% (C5). The
average total number of papillae of the tail were: 25.6 (JR) and 26.1 (C5) for
the ventral surface and 20.72 (JR) and 21.33 (C5) for the dorsal papillae. The
comparison between the percents of the cercariae of two S. mansoni strains with
more than 1 papillae on the anterior ventral quadrants A or B (94% JR and 34%
C5), resulted with significant differences (P < 0.05).
PMID- 9640683
TI - [Acuariosis in Numida meleagris (Aves: Numididae)].
AB - A case of gastric nematodiasis is described in a gineafowl (Numida meleagris)
from the Municipal Zoo, Presidencia Roque Saenz Pena (Chaco) Argentina. Nematodes
obtained from the glandular stomach were observed in optic microscopy. According
to their morphometric characteristics and location in the definitive host, were
identified as belonging to the family Acuariidae, subfamily Acuariinae, species
Dispharynx nasuta Rudolphi, 1819.
PMID- 9640684
TI - [Pediculosis capitis, a permanent and renewed problem].
AB - Pediculosis capitis is still a world-wide public health problem. Pediculus
humanus capitis, the agent, is a permanent and specific human blood-sucking
ectoparasite extended throughout the world. By the end of sixties and begin of
seventies an important increase of prevalence of this parasitose was observed in
many countries and lice infestation throughout the world was estimated to run
into hundreds of millions. Decline of personal hygiene, increased promiscuity and
long hairstyle, particularly in adolescents and young people seemed to mark the
beginning of this new situation. At present pediculosis capitis not only affects
low socio-economic groups, but middle and high level groups. Several observations
have shown a clear relationship between long hair and pediculosis capitis.
Prevention of pediculosis capitis is supported by community health education,
stressing the personal hygiene, the use of reasonable short hair and frequent
washing of head.
PMID- 9640685
TI - [Prevalence of Blastocystis hominis infection in schoolchildren from Bolivar
City, Venezuela].
AB - Blastocystis hominis is found in about 25% of feces in normal asymptomatic
people. Its pathogenic role is still discussed. A prospective study was performed
to determine the prevalence of B. hominis infection in schoolchildren from
Bolivar City. We evaluated 446 children, between five and fourteen years old,
both sexes, using direct examination of feces and Willis Method. They were also
evaluated clinically. Results showed that B. hominis had a prevalence of 16.8%.
We did not find a statistically significant association between sex (P > 0.05) or
age and infection with B. hominis (x2 = 1.94 g.l = 4). In 39 schoolchildren
(52.0%) we identified other parasites along with B. hominis, the most frequent
was Trichuris trichiura as helminth and Giardia lamblia as protozoan. We observed
B. hominis alone in 36 cases (48.0%). There was a spectrum of clinical symptoms
in 41 (54.7%) of all children evaluated. Diarrhea was the most frequently
clinical manifestation observed. Other studies are necessary to determine
clinical relevance of B. hominis in school population in Bolivar City.
PMID- 9640686
TI - [Frequency of human trichinosis in Concepcion and Arauco, Chile: study in
autopsied persons at the Concepcion Medico-Legal Service. June 1996-March 1997].
AB - The frequency of trichinosis was determined in 300 dead persons, residents in the
provinces of Concepcion and Arauco, and requiring necropsy at the Servicio Medico
Legal of Concepcion. Diaphragm muscle samples were taken from June 1996 to March
1997. The diagnosis was made by trichinoscopy and artificial digestion
techniques. Five samples (1.67%) were positive. There was not differences between
sexes. Positive cases were found mainly among 30 to 49 years old people belonging
to middle-lower class. Both diagnostic techniques showed different sensitivity as
a consequence of the parasitic load and on the contrary, the artificial digestion
was less sensitive when the cyts were fully calcified.
PMID- 9640687
TI - [Contribution to the morphological description of Tylodelphys barilochensis and
Tylodelphys crubensis (Trematoda, Diplostomidae) encephalon parasites of Galaxias
maculatus (Teleostei, Galaxiidae)].
AB - Taxonomic characteristics, for species identification, of metacercarie of T.
barilochensis and T. crubensis found in the encephalon of the fish Galaxias
maculatus, not included in the original descriptions, particularly those
concerning to the excretory system, are described.
PMID- 9640688
TI - [Development of tympanoplasty].
PMID- 9640689
TI - [The results of tympanoplasty with titanium prostheses].
AB - In order to improve the hearing results of tympanoplasty, we performed the
operation on 113 cases (124 ears) by using ossicular replacement prostheses made
of Titanium. The results demonstrated that among all the operated ears, 73/124
(58.9%) had obtained a narrow gap (< 20 dB HL) between BC and AC, 89/124 (71.8%)
had regained socially acceptable hearing ability. The total effective rate of
hearing gain (> 10 dB HL) was 115/124 (92.7%). No reject reaction and recurrent
cholesteatoma were found. This operation method, based on animal experiments and
applied anatomic study of human suprastapedial structure, resulted in a high
effective rate and maked hearing improvement with a relatively large magnitude.
It was because of the application of a new material-Titanium, which has high
biocompatibility with human body tissues. The ossicular replacement prosthesis
was appropriately designed and delicately manufactured. It fitted well and could
be tightly joined to the suprastapedial structure, and uneasy to be displaced. In
addition, we adopted the method of enlarging tympanic isthmus, that lead to well
aeration in mastoid and attic, thus set the tympanic membrane to the best state
of mobility. All these contributed to the effective hearing gain.
PMID- 9640690
TI - [Cholesterol granulomatous tympano-mastoiditis].
AB - In order to investigate the early diagnosis and proper management of the
cholesterol granulomatous tympanomastoiditis, 6 cases verified by pathology and
surgery were reviewed. All of these cases had a longterm or a historical otitis
media. Among them, different clinical features were presented, such as chronic
serous otitis media, idiopathic blue eardrum, or as a primary occupying lesion of
the middle ear. Depend on the extension of the disease, surgical procedure varied
in the 6 cases, including exploratory tympanotomy, ventilation tube insertion,
antroatticotomy, simple mastoidectomy, and radical mastoidectomy. Postoperative
follow up for at least one--7 year showed no recurrence, and hearing improvement
in 5 cases. The clinical basis of the diagnosis and management of this disease
were also discussed.
PMID- 9640691
TI - [Mastoid pneumatization and secretory otitis media].
AB - 75 ears of 44 patients with secretory otitis and 80 ears of 40 patients with
normal ear were observed and reserched. All of the cases were received X-ray
examination of mastoid process in Schuller's lateral projection. The size of the
air cell system was obtained by planimetry: the method what was originally
devised by Diamant. The outline of the mastoid air cell system (MACS) was marked
out on the radiograph and then transferred to graph paper where the number of mm2
can be counted directly. According to measuring the planimetric area of MACS. The
mastoids were divided into two categories: pneumatization type and
nopneumatization type. 5 of 69 ears with pneumatization mastoid (7.2%) were
secretory otitis, while 70 of 86 ears with nopneumatization (81.4%) were
secretory otitis. It was significantly different (P < 0.001) camparing the number
of ears with secretory otitis. We believe that the degree of mastoid
pneumatization is associated with the occurring and prognosis of secretory
otitismedia.
PMID- 9640692
TI - [A report of 164 cases of Bell's palsy].
AB - In order to research the relationship between various methods of treatment and
their prognosis on Bell's palsy, 164 cases of Bell's Palsy were reviewed.
According to the results of ENoG test, 164 cases were divided into three groups
A, B1 and B2. Group A: the paretic side ENoG loss was less than 90%, group B1:
the ENoG loss was more than 90% and without surgical decompression of facial
nerve, group B2: the ENoG loss was more than 90% and with surgical decompression.
All of the patients had follow up for 1-3 years or even longer after onset. The
grades of recovery of facial function were evaluated by modified classification
system as originally proposed by Portmann. The facial function of 77 cases of
group A were recovered satisfactorily except 3 patients, the average points were
19.22 +/- 1.18. The average points of group B1 (41 cases) and B2 46 cases were
14.4 +/- 3.49 and 15.4 +/- 2.08 respectively. Comparing the results with group
B1, B2 and A, there was no statistical significant difference (P > 0.05) between
group B1 and B2, but the results of group A were statistically significant better
than group B1 and B2 (P < 0.01). The prognosis of Bell's palsy might mainly
depend on the degree of degeneration of facial nerve. A satisfactory recovery can
be expected when ENoG test loss was less than 90%. If ENoG loss was more than
90%, neither surgical decompression nor steroids therapy could change the
prognosis statistically.
PMID- 9640693
TI - [Nasal septal deviation in fetuses].
AB - To investigate the etiology of nasal septal deviation, twenty-four fetal
sinonasal specimens aged between 8-40 weeks of gestation were studied under light
microscopy. Sixteen fetal heads aged between 32-40 weeks were examined using 2.7
mm 5 degrees Wolf endoscope. Five of 24 fetal sinonasal specimens were confirmed
histopathologically to have deviated nasal septum. 1 of 16 fetal heads was
considered to have nasal septal deviation. The existence of nasal septal
deviation in fetuses was confirmed. To explain the embryogenesis, we suggested
that maldevelopment of vomeropalatal complex is responsible for the formation of
nasal septal deviation in fetuses.
PMID- 9640694
TI - [Bromodeoxyuridine immunohistochemical observation of sensory epithelium repair
after ototoxic destruction in the crista ampullaris of guinea pigs].
AB - In this in vivo study we investigated the proliferation of crista ampullaris in
guinea pigs after Gentamicin intoxication by BrdU immunohistochemical observation
and semi-thin sections. The experimental animals were given a single
intraperitonial injection of BrdU at a dose of 150 mg/kg body weight before
subsequently killed at 1, 3, 7, 14 and 22 day post-treatment (PT). Supporting
cell proliferation was evident by BrdU immunoreactivity in the chromatin material
of dividing cells at 7 and 14 day PT. The results demonstrated that the crista
ampullaris of guinea pigs had repaired by supporting cell mitosis.
PMID- 9640695
TI - [DNA replication and cellular proliferation in the noise damaged basilar papillar
of chicks].
AB - An acoustic trauma model for study of the repair of the auditory epithelia was
established in postnatal 8-14 days chicks. The animals were continuously exposed
to the wide band noise at 115 dB (A) for 72 hours. The tracer of DNA replication
[3H] thymidine (3H-dR) was given in vivo or in vitro during or after exposure.
The basilar papilla were cultured and processed with autoradiographic technique.
The results demonstrated that at 48 hours following initial labelling of tracer,
the incorporation of 3H-TdR was found over the nucli of supporting cells (or
precursor cells) in the injured region of basilar papilla. The labelled hair
cells appeared at 96 hours near the labelled supporting cells. Until the fifth to
sixth days of culturing, the regenerated hair cells were still immature
morphologically. No sign of labelled hair cells were detected in the control
animals. Our findings indicated the potential capability of cellular
proliferation and DNA replication in damaged auditory epithelia in vitro. Some
kind of supporting cells in damaged region could be the precursors for
regenerating hair cells. The positive cells labelled with 3H-TdR migrated to the
surface of basilar papilar and differentiated into hair cells eventually.
Therefore, it could be speculated that a homogeneous relationship may exist
between labelled supporting cells and labelled hair cells.
PMID- 9640696
TI - [A study of tracheal defect repair in rabbits with collagen-hydroxylapatite].
AB - An artificial material composed of collagen-Hydroxylapatite (C-HA) was used to
repair the tracheal defect of rabbits. There was no reaction, no absorption and
no particle detachment after the C-HA was implanted. We also found that the
tracheal mucosa could grow over the surface of C-HA. The result suggested that
the C-HA can be used as a material for repairing the tracheal defect of the
tracheostenosis.
PMID- 9640697
TI - [Histiocytosis X of the temporal bone].
AB - Histiocytosis X (HX) is a rare disease. There are many questions and debates in
its etiology, pathology, clinical type and therapy. To enhance the recognition of
otolaryngologists in HX of the ear and temporal bone and the level of diagnosis
and therapy, 30 years' results of 21 patients with HX of the ear and temporal
bone proved by histiopathology were reviewed, 18 patients were cured (85%), 6
cases were residual of diabete insipidus and dwarfism (28%), 3 cases died (14%).
The clinical classification system should be based on the extention of diseases.
Surgical curettage, radiation therapy are mainstays of treatment; chemotherapy
should be used in patients with aggressive and disseminate diseases and etiology
of histiocytosis should be studied on immune system that potentially aid in
therapy.
PMID- 9640698
TI - [Medical imaging research on idiopathic hemifacial spasm].
AB - In order to have a medical imaging examination for idiopathic hemifacial spasm
before surgery, we designed a new method by using vertebroarterial DSA and
vertebroarterial CTA based on an aired cisternapontis, 36 patients were examined
since 1989 and the compression of the facial nerve from brain stem to porus
acousticus internus was showed clearly in all the cases. The arteries responsible
for the compression were cerebellar inferior posterior (55.6%), cerebellar
inferior anterior (44.4%), auditory internus (25.0%) and vertebroarterial
(11.1%), 36% of all the cases had more than one responsible arteries, 22.2% cases
had only one compression point, 38.9% had two points, 25.0% had 3 and 13.9% had
more. 85.7% of the compression points located in the root zone and 14.3% near the
porus acousticus internus. 24 cases were treated with decompression surgery, it
indicated that the compression conditions just met the medical imaging
examinationg results. After surgery the symptom disappeared in 23 cases and
remarkably released in one case with no death case. We believed that this method
might be helpful to idiopathic hemifacial spasm decompression surgery and other
surgeries in the CP angle.
PMID- 9640699
TI - [Treatment outcome of 1,000 cases of endoscopic sinus surgery].
AB - To assess the treatment outcome of endoscopic sinus surgery (ESS), 1,000 patients
with chronic sinusitis and nasal polyp treated between November 1991 and January
1995 were included in this study. Among them, 754 patients (64.8%) had previous
operations from 1 to 25 times with an average of 3.7. Before ESS, axial and
coronal CT scans were obtained (window width: 1,000 HU, window level: +90 HU;
section thickness: 2 mm with 12 to 16 sections). Patients with clinical stages
from I to IV were 9.9%, 21.0%, 15.0% and 54.1% respectively. Bilateral ESS was
performed in 95% patients, septoplasty in 27.6%, middle meatal antrostomy in
78.5%. The clinical cure rate was 84.0%, 557 patients were considered as primary
healing, 283 patients delayed healing and 160 patients had persistent
inflammation. Complications were noted in 18 patients. Bleeding during ESS varied
from 10 to 1,800 ml (average 180 ml). The indications, preoperative evaluation,
control of bleeding, prevention of complications and prognosis were discussed in
detail. The article indicated that the important factors to increase the cure
rate are postoperative follow-up and systematic treatment.
PMID- 9640700
TI - [Nasal polyps of olfactory sulcus].
AB - To explore the origin of olfactory sulcus polyp (OSP) and observe the recovery of
olfaction after functional endoscopic sinus surgery, fifty-nine olfactory sulcus
polyps in 31 patients were reviewed. The origin of OSP was carefully observed. In
these patients 69.5% (41 sides) originated from the mucosa of posterior ethmoid
sinus, including the superior meatus (23 sides) and ethmoid cells near the ostia
(18 sides). OSP originated from middle turbinate (8 sides) and superior turbinate
(4 sides). Six OSP originated from the mucosa of both ethmoid and sphenoid sinus.
Olfactory changes were dynamically observed after endoscopic sinus surgery in 26
patients. The smell improved significantly in 26 sides (52.0%) within three
months. The olfaction improved slowly in those patients with recurrent polyps and
polysinusitis associated with polyps. We suggest that minimal endoscopic sinus
surgery is the treatment of choice for OSP.
PMID- 9640701
TI - [Extended vertical partial laryngectomy for treatment of the glottic cancer with
T3 category].
AB - From June 1981 to December 1992, 32 patients of glottic cancer with T3 category
were treated by extended vertical partial laryngectomy, i.e. vertical
laryngectomy plus the resection of the arytenoid and part of the cricoid plate.
The laryngeal defect was reconstructed by an osteomuscular flap. The 3- and 5
year survival rates were 78.1% and 73.9% respectively. The decannulation rate was
81.3%. The voice was satisfactory in 84.3%. All patients resumed mouth-food
taking. The authors conclude that selective glottic cancer of T3 category treated
with extended vertical partial laryngectomy, which preserves the functions of the
larynx and improves the quality of the life, is feasible and acceptable.
PMID- 9640702
TI - [The surgical treatment for the epiglottic cancer extended to the base of
tongue].
AB - 26 cases of the epiglottic cancer extended to the base of the tongue were studied
retrospectively. Among them, 14 were male and 12 female. The age varied from 43
to 62. Besides two cases who underwent total laryngectomy, the other twenty-four
were treated with supraglottic horizontal partial laryngectomy or
horizontovertical subtotal laryngectomy and resection of part of base of the
tongue. 11 cases received bilateral radical neck dissection (RND) and 10 cases
unilateral RND simultenously. The results showed twenty-four cases had resumed
speaking ability, twenty had been decannulated and restored the laryngeal
functions. The 5-year survival rate was 57.9% (12/19). It was concluded that
transpharyngeal approach was reasonable for supraglottic horizontal partial
laryngectomy associated with the resection of the base of the tongue.
PMID- 9640703
TI - [Endoscopic CO2 laser treatment for the decannulation difficulty after vertical
laryngectomy].
AB - Sixteen patients with the decannulation difficulty after vertical laryngectomy
were treated by endoscopic CO2 laser. The rate of decannulation was 87.5%
(14/16). The curative effect was stable after 1-3 years. The causes of the
decannulation difficulty included the over growth of granulation tissue, scar
formation and bulky of the muscle flap. The result showed that endoscopic CO2
laser is an effective modality in the treatment of the decannulation difficulty
after vertical laryngectomy.
PMID- 9640704
TI - Telemedicine and developing countries. A report of study group 2 of the ITU
Development Sector.
AB - While there are significant potential advantages and benefits from telemedicine,
the evidence of its cost-effectiveness and sustainability is meagre. This is
because much of the telemedicine activity so far has been in the form of pilot
projects of demonstrations in universities and hospitals with subsidized funding
from government or other sources. The number of self-sustaining, commercial
applications of telemedicine is still very small. Telemedicine undoubtedly yields
cost savings in certain circumstances, but often the savings and benefits accrue
to those who do not have to pay for the service. Thus, few service providers have
found a way to recover their costs (and make a profit) from those to whom they
provide their service. Even fewer countries have actually budgeted for the
provision of telemedicine as a service widely available to their citizens.
Nevertheless, with the rapidly declining cost in hardware and telecommunications,
the level of interest and the corresponding activity in telemedicine is rising
rapidly. Most of the telemedicine experience to date has been in the
industrialized world. It is apparent that the first requirement of developing
countries is for more information about telemedicine, what it is, and how it
might be able to help solve some of the shortages in medical and health care.
Given the potential of telemedicine to facilitate the provision of medical
information and health care in rural areas, it seems useful for developing
countries to undertake pilot projects in order to evaluate its potential and cost
benefits. The results of such pilot projects could be part of the development of
a national health for all policy which takes telemedicine into account. In view
of the other priorities of developing countries, especially those of the least
developed countries, financing telemedicine activity is likely to remain a
challenge for some time to come. Funding from external donor agencies may well be
necessary, but local commitment and participation in pilot projects is essential
if the project is to have a chance of success. As telemedicine requires a
multidisciplinary approach, the active participation of telecommunication
operators must be assured. Despite some false starts in the deployment of
telemedicine as a continuing service to the general population--as opposed to a
few well-to-do clients--telemedicine has great potential to improve access to
health care and to contain costs in developing countries.
PMID- 9640705
TI - A survey of research in telemedicine. 1: Telemedicine systems.
AB - Published work in telemedicine has been surveyed in order to consider the range
of current research, highlight some pitfalls and point out areas where it seems
that more work is required. This article deals with tests of the safety and
efficacy of telemedicine systems. This work can be seen as moving through three
phases: first, identify the technical specification of equipment required for the
particular telemedicine application; second, test that this is appropriate in
particular settings; third, establish a set of standards and guidelines to ensure
that the telemedicine system is used to the best advantage. Work in teleradiology
seems to be in the second phase. Work in teledermatology, for example, is still
in the first phase. Telemedicine is an important and growing area of academic
research. The quality of the research ought also to be increasing. While there
have been a number of well designed, robust studies with clear conclusions that
show the value of telemedicine in certain settings, much more remains to be done.
PMID- 9640706
TI - The legal and ethical aspects of telemedicine. 2: Data protection, security and
European law.
AB - The electronic record may be subject to abuses that can be carried out on a large
scale and cause great damage. A wide range of data protection and information
security measures will need to be taken to ensure the quality and integrity of
such records. A European Union directive was formally adopted in 1995 which sets
the obligations of those responsible for data processing as well as a number of
important rights for individuals. The responsible teleconsultant or medical
officer, as the data controller, must make sure these measures are enforced. In
the case of the transmission of medical records to another location, the original
data controller may remain liable for abuses. But as different elements of the
records are spread throughout the different departments of a hospital or across
different geographical locations, it may become difficult to ascertain who is
responsible for protecting and controlling what. To this end, the designation of
liability by contractual means, between the hospital and remote users of a
telemedicine network, would be the clearest and most straightforward way of
achieving uniformity and predictability in terms of the distribution of
responsibility for data protection and security.
PMID- 9640707
TI - Teleradiology: a review.
AB - Teleradiology, like telemedicine generally, has arisen because of the shift to
digital communication and the demand for equal access to medical care. Unlike
much of telemedicine, teleradiology can be shown to be cost-effective in many
situations, particularly if the alternatives are to transport the X-ray film to a
radiologist or to use the services of a visiting radiologist ('circuit riding').
A teleradiology system consists of an image-acquisition section and an image
display section, connected by a communications network. Considerable technical
and clinical standardization work has been carried out (e.g. by the American
College of Radiology) and commercial teleradiology systems are now available from
a number of manufacturers. Up to 1994, more than 7000 teleradiology systems had
been sold by the two largest manufactures. Technology trends suggest that it will
soon be common for clinicians to view digital radiographs from outside radiology
departments and probably from outside a hospital environment as well.
PMID- 9640708
TI - Patient satisfaction with realtime teledermatology in Northern Ireland.
AB - Teledermatology consultations were organized between two health centers and two
hospitals in Northern Ireland using low-cost videoconferencing equipment. A
prospective study of patient satisfaction was carried out. Following each
teleconsultation, patients were asked to complete a questionnaire assessing their
satisfaction with the service. Over 22 months, 334 patients were seen by a
dermatologist over the video-link, and 292 patients (87%) completed the 16-item
questionnaire. Patients reported universal satisfaction with the technical
aspects of teledermatology. The quality of both the audio and the display was
highly acceptable to patients. Personal experiences of the teledermatology
consultation were also favourable: 85% felt comfortable using the video-link. The
benefits of teledermatology were generally recognized: 88% of patients thought
that a teleconsultation could save time. Patients found the teledermatology
consultation to be as acceptable as the conventional dermatology consultation.
These findings suggest overall patient satisfaction with realtime
teledermatology.
PMID- 9640709
TI - Pathologists' attitudes to implementing telepathology.
AB - If pathologists will benefit so much from using telepathology, why is it taking
so long to be introduced? This question has been discussed between experts, but
the potential users are rarely asked for their opinions. A questionnaire was sent
to the 256 members of the Austrian Society of Pathology; this addressed general
aspects of telemedicine, telepathology in frozen-section services and expert
consultation, videoconferencing technologies, teleteaching and teletraining. The
response rate was 46%. In general, the pathologists thought that telemedicine
could become valuable in their daily routine. However, pathologists were most
afraid of sampling errors in remote diagnosis and would not readily accept an
alternative to the conventional method of looking at a sample. This is only
possible using realtime, remotely controlled microscopes. Telepathology systems
providing only still images would not be acceptable to most respondents. There
was interest in the use of videoconferencing for clinicopathological conferences.
Teleteaching and teletraining were seen as welcome additional techniques, but
were nevertheless judged unable to replace classical methods of teaching and
training.
PMID- 9640710
TI - Planning criteria for multicentre, multilingual telemedicine conferences.
AB - The international telemedicine conference Chinese TeleMed 96 was held in November
1996. This three-way teleconference included delegates in London (where the
international telemedicine conference TeleMed 96 was taking place) and medical
staff from one Beijing hospital and one Hong Kong medical faculty. In total, over
1000 health-care personnel across eight time-zones participated. The event
demonstrated that the quality of teleconferencing technology was suitable for
medical teaching, for providing medical consultations to remote locations and for
stimulating medical exchanges. In general, planning a telemedicine conference
requires a longer lead time, a wider representation of expertise in the
organizing committee and more financial resources than conventional conferences.
It is recommended that the aim and format of a telemedicine conference be
determined at least one year before the target date. Criteria for improving the
preparation of such conferences have been identified and a set of guidelines for
future conference organizers has been drawn up.
PMID- 9640711
TI - Videoconferencing and the hard of hearing.
PMID- 9640712
TI - The diffusion of telemedicine: theory into practice.
PMID- 9640713
TI - Telemedicine: university-level education in Finland.
PMID- 9640714
TI - Transmission of medical data from an aircraft.
PMID- 9640715
TI - A pilot study of tele-ophthalmology outreach services to primary care.
AB - We have begun a randomized study of tele-ophthalmology. General practitioners in
two participating health centres in the Negev region of Israel, serving a local
population of 40,000, were invited to participate. The study group consisted of
50 consecutive patients attending the general eye outpatient clinic and 50
consecutive patients suffering from various retinal diseases attending a hospital
outpatient clinic. The initial assessment was carried out via the tele
ophthalmology system. There was then a face-to-face re-examination of the same
patients, in randomized order, by the same ophthalmologist on the same day, at an
outpatient ophthalmology clinic.
PMID- 9640716
TI - Preliminary results from the Northern Ireland arms of the UK Multicentre
Teledermatology Trial: is clinical management by realtime teledermatology
possible?
AB - Results from phase 1 of the UK Multicentre Teledermatology Trial demonstrated the
diagnostic accuracy of realtime teledermatology using low-cost equipment. Phase 2
of the trial aimed to assess its effectiveness as a management tool for
dermatological disease. Teledermatology consultations were organized between two
health centres and two hospitals in Northern Ireland using low-cost
videoconferencing equipment. For 205 patients seen by a dermatologist over the
video-link a diagnosis and management plan were recorded. A subsequent face-to
face consultation was arranged on the same day to confirm the diagnosis and
treatment regime. A comparison of these management plans revealed that the same
plan was recommended in 64% of cases; the teledermatologist was unable to
advocate a suitable management plan in 19% of cases; a suboptimal treatment plan
was suggested by the teledermatologist in 6% of cases; and in 11% of cases, the
teledermatologist suggested an inappropriate treatment plan. These findings
indicate that appropriate clinical management was possible in approximately two
thirds of dermatology consultations via the video-link.
PMID- 9640717
TI - Transmission of electrocardiograms from a moving ambulance.
AB - Delay is the enemy for patients with acute myocardial infarction. It would be
helpful for the hospital cardiologist to interpret the patient's
electrocardiogram (ECG) before the arrival of the ambulance. The aim of our study
was to determine whether ECG transmission from an ambulance is feasible and to
assess the time savings. An ambulance was equipped with an ECG recorder, which
was connected to a notebook computer and coupled to a cellular telephone for
transmission to a hospital-based station. Paramedics needed 2 min (SD 0.5) to
record the ECG on the move and 34 s (SD 14) to transmit it. The ambulance arrived
15.5 min (SD 6.5) after reception. The time between arrival and ECG diagnosis,
for a control group patient, was approximately 9.5 min (SD 3.5). Therefore, pre
hospital ECG diagnosis took place 25 min (SD 7.5) before in-hospital diagnosis.
We conclude that ECG transmission from a moving ambulance is feasible, reduces in
hospital delays and allows faster triage in critical cardiac cases.
PMID- 9640718
TI - Trans-telephonic electrocardiographic monitoring--experience in India.
AB - A centre for trans-telephonic electrocardiographic monitoring (TTEM) was
established at the Escorts Heart Institute in May 1996. We have reviewed our
experience in the first 398 patients. There were 321 males (81%) and 77 females
(19%); their age range was 1 month to 95 years. Sixty-five per cent of patients
were from New Delhi, while the remainder were from other cities in India and
abroad. As well as follow-up of patients after discharge, the system was used for
the evaluation of chest pain, palpitation, chronic angina, arrhythmias, and
pacemaker implants. Out of 664 symptomatic transmissions, 510 (77%) were for
cardiac symptoms like chest pain (309), palpitation (90), uneasiness (61),
dizziness (28) and breathlessness (22); the other 154 (23) were for non-cardiac
symptoms like stitch pain and backache (51), typical chest pain (39), weakness
and fever (45), and sweating (19). The majority of patients with chest pain
(84%), palpitation (78%) and dizziness (75%) transmitted their electrocardiograms
within one hour of the onset of the symptoms. Out of 664 symptomatic
transmissions, 531 required either reassurance or drug-dose adjustment by
telephone and 97 were called to the outpatient department on an elective basis.
Immediate hospitalization was advised for 36 patients, for acute management of
their symptoms. TTEM was useful in avoiding 628 unnecessary visits to the
hospital, while 36 patients were immediately hospitalized for acute care.
PMID- 9640719
TI - Telemedicine in primary care in Israel.
AB - A primary-care teleconsulting system was established between an academic family
medicine centre and a clinic about 50 km away. The videoconferencing units were
connected at 384 kbit/s. Seven patients were examined by a physician in the
clinic and then examined by a consulting physician using the telemedicine system.
Four other patients were examined through the telemedicine system first and by a
local physician later. The telemedicine consultation solved five of the patients'
medical problems. The waiting period before receiving expert medical consultation
was reduced. There was full patient satisfaction regarding this method of
consultation, patient 'run around' was avoided and patients felt at ease. The
telemedicine consultation process improved the patient-physician bond and the
attending physician's level of confidence.
PMID- 9640720
TI - Cost-effectiveness analysis of telemedicine.
AB - There are a number of different costs associated with the development and
operation of telemedicine services. A model is proposed in order to assist in
strengthening the evidence base for telemedicine. It includes the following
components: project establishment costs; equipment costs; maintenance costs;
communication costs; staffing costs. All need to be considered in arriving at an
annual cost figure for operating a telemedicine service. The inclusion of all
these costs, prepared in the standard manner outlined in the model, will ensure
that a realistic cost figure is available when evaluating the cost-effectiveness
of a telemedicine service.
PMID- 9640721
TI - A randomized controlled trial of telemedicine in an emergency department.
AB - A prospective study of emergency department telemedicine was carried out at two
hospitals in northern New Jersey. One hundred and twenty-two patients met the
inclusion criteria. One hundred and four (85%) consented to participate, with 54
being randomized to the telemedicine group and 50 to the control group. Four
patients did not complete the protocol. No significant differences were seen
between the groups for: occurrence of 72 h emergency department return visits (0%
vs 0%); need for additional care (2.3% vs 2.4%); positive patient-physician
interaction (98% vs 100%); positive patient-nurse interaction (98% vs 98%);
positive overall patient satisfaction (98% vs 95%). The average patient
throughput time (time from admission to discharge) for the telemedicine group was
106 min; the average for the control group was 117 min. Telemedicine was found to
be a satisfactory technique for pre-selected emergency department patients and
was viewed by the physicians as an acceptable method of complementary care.
PMID- 9640722
TI - Image selection in static telepathology through the Internet.
AB - A telepathology study was carried out to examine the differences occurring when
the images were selected by an experienced pathologist, a junior pathologist and
a first-year resident. One hundred and fifty-five consecutive frozen-section
pathology cases were collected and sent for consultation to a remote experienced
pathologist using multimedia email. Local diagnoses (as reported in the files of
the Institute, not from the image selector) and remote diagnoses (based on the
images) were compared with those performed on paraffin-embedded sections.
Acquisition time and number of selected images were recorded for each case and
used to compare the different behaviour of the three local pathologists. Of the
155 cases sent by telepathology, four were considered insufficient for a
diagnosis by the remote pathologist and thus the diagnosis was postponed. In the
remaining 151 cases, the overall diagnostic agreement between remote and
definitive diagnosis was 96.7%. The results indicate that in the routine
diagnostic work of a frozen-section service, an inexperienced pathologist can
select images which are sufficiently informative for a remote diagnosis, in a
sufficiently short time.
PMID- 9640723
TI - Telematic electrodiagnosis from six laboratories in three European countries and
one Asian country.
AB - The results of an electrodiagnostic test, the electro-oculogram, recorded under
standardized conditions, were compared. Recordings were obtained from 70 normal
subjects in three European countries and 28 subjects in an Asian country. All
subjects were 18-34 years old. Equal numbers of male and female patients were
tested in each of six laboratories. There were no significant differences between
the results of the European laboratories. There were, however, significant
differences between the results of the European and the Asian laboratories, and
between the results from the male and female subjects in all laboratories. This
suggests the need for considering the possibility of male/female as well as local
variations in normal control values when telemedicine is applied on a global
scale.
PMID- 9640724
TI - Portable satellite telemedicine in practice.
AB - The US army's first portable telemedicine unit was built in 1993 and comprised a
'ruggedized' videoconferencing unit. The unit was initially used in the United
Nations' operations in Macedonia in February 1994 and subsequently in support of
the Mobile Army Surgical Hospitals in Haiti, but its dimensions made it suitable
only for locations where a move at short notice was unlikely. The second portable
telemedicine unit comprised a PC linked to an Inmarsat B earth station through a
modern. The unit allowed videoconferencing at 64 kbit/s. Three and a half years
of clinical experience with both units has shown this to be quite adequate for
the majority of clinical telemedicine. Portable telemedicine units have been a
major benefit to medical commanders in the field.
PMID- 9640725
TI - The development of a telemedicine laboratory as a medical faculty resource.
AB - A telemedicine facility was established for the Faculty of Medicine of the
University of Aberdeen and developed as a laboratory to help ensure a scientific
approach to the implementation of telemedicine. Once a service application has
been positively evaluated and established then it should be funded and delivered
outside the laboratory, thus freeing up time and resources for the evaluation of
new areas. Since it would appear that the practice of telemedicine is here to
stay, it would also seem reasonable to suggest that an introduction to
telemedicine should be included in the medical undergraduate curriculum.
PMID- 9640726
TI - Teledermatology--high technology or not?
AB - As an alternative to attending a conventional dermatology clinic, patients had a
high-resolution conventional photographic image taken by a professional medical
photographer. The photographic images were viewed by a dermatologist together
with referral details from the general practitioner and any other relevant
information from the patient's notes. From the images, a dermatological diagnosis
was derived and a management plan for each patient instituted. After treatment,
histological assessment of the tumours allowed diagnostic accuracy to be
determined. The preliminary diagnostic accuracy (71%) was greater than that of
the referring general practitioners (49%). However, when the diagnostic ability
of the method to detect the nature of malignant lesions was examined,
telemedicine was able to detect malignancies in 94% of cases compared with only
70% detected by general practitioners. The results of the present study indicate
that teledermatology is achievable using a low-technology, low-cost approach.
PMID- 9640727
TI - Psychotherapy supervision conducted by videoconferencing: a qualitative study of
users' experiences.
AB - Psychiatry residents in Norway have 70 hours of mandatory psychotherapy
supervision to develop insights into the therapeutic relationship. Six
supervision pairs (six candidates and two supervisors) conducted five
videoconferencing-based supervision sessions (384 kbit/s) and five face-to-face
sessions alternating weekly for 10 sessions. Following completion of the 10
sessions for candidates and supervisor B, and the 50 sessions for supervisor A,
all subjects completed a semi-structured interview within two weeks. The eight
subjects reported a wide range of experiences and attitudes. The results
suggested that the quality of supervision can be satisfactorily maintained by
using videoconferencing for up to half of the 70 hours required. The precondition
for this estimate is that the pair in question have met face to face and
established a relationship characterized by mutual trust and respect. Further
studies, which include supervision pairs not having previously established
relationships, are needed in order to indicate the generality of this
precondition. The most obvious implication of this study is the potential for
implementing decentralized models for recruiting and educating psychiatrists.
PMID- 9640728
TI - The assessment of cognitive function in the elderly using videoconferencing.
AB - People over the age of 65 were recruited from an inner-city old-age psychiatry
service. Subjects had a structured interview (the CAMCOG test) by
videoconferencing, and also face to face, by an investigator blind to the results
of the test in the other mode. Reassessments were carried out within one week of
the initial assessment. Eleven subjects were initially enrolled in the study and
eight completed both modes. The number of patients in this study is very small
but the results suggest that the CAMCOG test can be used reliably over a
videoconferencing system without major modification.
PMID- 9640729
TI - Use of video in the informed consent process.
AB - We created a video-tape about the concept of telemedicine for informational and
educational purposes. Two video-tapes, one with and one without the informed
consent segment, were distributed to each of the Kentucky TeleCare sites. On the
day of their teleconsultation, patients were asked to watch the video-tape (with
the version containing the informed consent segment) before signing the informed
consent to participate. Site coordinators then asked patients whether they had
any specific questions about telemedicine. To date, patients have reported high
levels of satisfaction with this method of consultation, using telecommunications
technology to deliver health care.
PMID- 9640730
TI - The Austrian Academic Computer Network and its usefulness for teleradiology.
AB - To study the value of the Austrian Academic Computer Network (ACOnet) for
teleradiology, 1740 test image data-sets and 620 image data-sets were exchanged
between the departments of diagnostic radiology of the Universities of Innsbruck
and Graz using the ACOnet service. Data transmission was reliable and fast with
an average transfer capacity of 170 kByte/s (range 94-341). During the test
phase, no major problems with image transfer occurred. Assuming that problems
like security of patient data-sets, data compression and data verification can be
solved, the ACOnet service would be a useful additional tool for telemedicine
applications throughout Austria and eastern Europe.
PMID- 9640731
TI - An Internet station for telemedicine in the Azerbaijan Republic.
AB - We have established the first medical Internet and telemedicine station in the
Azerbaijan Republic. The station began work on 16 June 1997. In the next three
months a list of local and international medical electronic resources was drawn
up and contacts made with medical informatics organizations and medical
libraries. Five telemedicine consultations were carried out with Moscow clinics
in specialties such as cardiology, ophthalmology, endocrinology and surgery. The
quickest and most cost-effective way of improving medical care in Azerbaijan is
to provide medical information support using modern telecommunications.
PMID- 9640732
TI - Telemedicine and medical care to ships without a doctor on board.
AB - Providing medical assistance to ships at sea was probably one of the first
practical applications of telemedicine. At present, about 200 different
organizations worldwide give medical assistance to ships without a doctor on
board. The activity of the Foundation Centro Internazionale Radio Medico (CIRM),
which probably has the largest experience in the world of telemedicine applied to
seafarers, is reviewed. Medical assistance to seafarers has not improved in
parallel with advances in medicine and telecommunications. Possible initiatives
for improving teledelivery of medical assistance to seafarers are discussed.
PMID- 9640733
TI - Value of a low-cost telemedicine link in the remote echocardiographic diagnosis
of congenital heart defects.
AB - We established a low-cost telemedicine link from a district general hospital to
the regional paediatric cardiology department about 120 km away. The link was
used to transmit echocardiographic images of newborn infants suspected of having
congenital heart disease (CHD) to the referral centre, with simultaneous video
and audio contact for consultation. Echocardiograms were transmitted for 61
patients suspected of having CHD, aged from 1 to 42 days. The transmitted images
were of adequate quality for the paediatric cardiologist to make a diagnosis in
59 (97%). Congenital heart abnormalities were diagnosed in 38 (64%). Twelve
patients (20%) had major CHD diagnosed on the transmitted scan and required
transfer to the regional cardiology unit either urgently or electively after
initial measures to stabilize the patient. Our findings suggest that, for babies
suspected of having CHD, ultrasound images of diagnostic quality can be obtained
and transmitted using a low-cost telemedicine system.
PMID- 9640734
TI - Broadband multimedia for education.
AB - Over the next five to ten years the accelerating development of computing and
broadband networks will lead to a revolution in the ways in which health care is
delivered. Patients will spend less time in the great institutions of the
tertiary hospitals and the illnesses taking them there will assume a different
pattern. The new information technologies will foster the emergence of general
practices with a new emphasis on keeping patients in their communities for
medical management. Knowledge exchange and delivery--to both patient and
practitioner--will therefore become an increasingly important component of the
health-care system in the next millennium.
PMID- 9640735
TI - Nurse reactions to a prototype home telemedicine system.
AB - We have studied nurse reactions to a prototype home health telemedicine system.
The system used interactive video through the local cable television network. Six
nurses were directly involved with telecare video-visits. There were 54 patients.
The average age of the patients was 76 years (range 21-101). Thirty-six (67%)
patients were female and 18 (33%) were male. The patients had an average of 4.6
different diagnoses (range 1-16). They were also on a very wide range of
medications (mean 9.9, range 2-23). Nurses overwhelmingly felt the system was
effective for what this particular project was trying to accomplish. They were
enthusiastic about the prospects of practising nursing by telemedicine, even
though they had reservations about aspects of the particular system being used.
Their main complaints were about limitations of the software and limitations of
the telecommunication system that linked them to the patients.
PMID- 9640736
TI - Cognitive behaviour therapy via interactive video.
AB - Interactive video has been identified as a potential delivery medium for
psychotherapy. Interactive video may restrict the range of both verbal and non
verbal communication and consequently impede the development of a therapeutic
relationship, thus influencing the process and outcome of therapy. A single case
study explored the feasibility of the provision of congnitive behaviour therapy
using interactive video with a client diagnosed as having mixed anxiety and
depressive disorder. A range of outcome measures were included together with an
independent psychiatric assessment prior to, and on completion of, therapy.
Different levels of outcome were also examined: clinical, social, user views and
administration. Outcome measures indicated a reduction in psychopathology and
some modification of dysfunctional attitudes, with no apparent impairment of the
working alliance.
PMID- 9640737
TI - Practical evaluation of telemedicine systems in the real world.
AB - There are six key questions that need to be asked before the evaluation of any
telemedicine project. These are: who, why, what, when, where and how? Evaluation,
and the subsequent communication of the results, is central to the development
and implementation of any telemedicine system. As telemedicine technologies and
processes gradually mature the extent and breadth of evaluations relevant to
these technologies will undoubtedly improve and it is to be hoped that
telemedicine systems will prove themselves as clinical tools.
PMID- 9640738
TI - Hospice care using home-based telemedicine systems.
AB - A pilot study of telenursing for terminally ill patients at home was launched as
a collaborative effort between KUMC and the Kendallwood Hospice. The service used
the public telephone network. Interactive video equipment was installed in the
homes of three nurses who received after-hours calls and in the homes of six
hospice patients living in either Kansas or Missouri. Data concerning the
utilization patterns were gathered for two separate three-month periods. Patients
and caregivers reported general satisfaction with the telehospice system. Both
the nurses and social worker providers became comfortable about video-calls.
Nurses conducted video-assessments to determine whether an 'in person' visit was
necessary. This was particularly helpful for rural patients who were living a
long way from the base station. In addition, Kendallwood serves an urban
population and, in certain areas, night-time nursing visits raise safety
concerns.
PMID- 9640739
TI - A pan-European social alarm system.
AB - SAFE 21 is a pan-European research and development project which will take social
alarms into the twenty-first century. It is run by a consortium of eight
organizations, with financial support from the European Commission. SAFE 21 will
use existing infrastructure to deliver a much broader range of services and
extend availability to users who are currently excluded. The project aims: to
develop a social alarm that will work from anywhere inside the home, using a neck
worn speech-pendant and outside the home making use of radio cellphone and global
positioning technology; to demonstrate how telemedicine can be incorporated at
marginal costs, by exploiting the existing social alarm infrastructure; to
demonstrate a shared control centre that facilitates emergency services, medical,
welfare and social professionals working together to support a broad-based social
alarm system; to provide access to social alarms for deaf users, who are
currently excluded.
PMID- 9640740
TI - Telepsychiatry: an island pilot project.
AB - A telemedicine link was established in 1996 between the island of Inishmore and
the department of psychiatry in University College Hospital, Galway. The link was
mainly used to facilitate emergency consultations between patients on the island
and the duty psychiatrist, always at the request of the island's general
practitioner. Nine patients were referred for assessment in this manner over
eight months. Three patients had their first psychiatric contact and assessment
through the video-link, and were followed up as outpatients via the link to
eventual resolution of the episode of illness and discharge at the outpatient
clinic. Our experience has been that videoconferencing systems are acceptable and
satisfactory for patients and staff alike.
PMID- 9640741
TI - The clinical and economic advantages of remote, community-based physiological
assessment.
AB - A prospective study documented the nutritional intakes of a large cohort of
pregnant women living in Portsmouth and investigated the independent
relationships of smoking, dietary intake and other maternal socio-economic
factors on outcome and cardiorespiratory function of the child during sleep at
home at three weeks and three months of age. Unattended overnight
cardiorespiratory recording was performed and the data stored in local memory
before transmission on demand via modem to Oxford next morning. The telemetry of
the physiological data, entirely managed by part-time community nurses in
Portsmouth, was very successful. Despite some losses, which included transmission
failures, electrode or lead disconnection, and monitor malfunction, 92% of the
physiological data were analysed at Oxford. Personalized physiological monitoring
in the community provides an opportunity for new evidence bases that will enable
a new level of individualized care.
PMID- 9640742
TI - Cost evaluation of a telepsychiatry service in northern Queensland.
AB - We conducted a simple comparison of the costs associated with delivering a mental
health service by telepsychiatry and by conventional methods. The telepsychiatry
rural outreach service was delivered to a mining town 900 km from the regional
hospital in Townsville. When the telemedicine service was well established, 40
cases a month were seen for general adult psychiatry, four for child and
adolescent mental health, four for psychology and two for forensic services.
Costs and quality-of-life issues were considered. The savings to the health
authority were estimated to be $85,380 in the first year and $112,790 in
subsequent years, not allowing for maintenance and equipment upgrading. We also
estimated a 40% reduction in patient transfers due to the introduction of
telemedicine. Based on the previous year's figures of 27 transfers at $8920 each,
this would produce an annual saving of $96,336 for the Royal Flying Doctor
Service. The results of the study showed considerable savings from reduced travel
by patients and health-care workers.
PMID- 9640743
TI - Teleradiology: results of a questionnaire of German radiologists.
AB - A questionnaire was sent by mail to 4400 radiologists (i.e. to at least 1000
radiological institutions). The response rate was about 5%. The results showed
that 47% of respondents felt well informed about teleradiology, 49% not enough
and 3% not at all. Image and report transfer as well as interfaces to reference
databases, educational applications, technical quality surveillance and product
support (maintenance) were considered to be increasingly important areas. Smaller
institutions (1-3 doctors) judged expert consultation as more important than
bigger institutions. Standardization, system stability and data security were
demanded as well as guidelines, for example concerning the linking of report and
image, correct documentation and required image quality. Technically most demands
can be fulfilled today but this technology is not yet commonly included in
teleradiology systems.
PMID- 9640744
TI - The experience of the Royal Children's Hospital Mental Health Service
videoconferencing project.
AB - In April 1995 the Royal Children's Hospital Mental Health Service in Melbourne
piloted the use of videoconferencing in providing access for rural service
providers and their clients to specialist child and adolescent psychiatric input.
What began as a pilot project has in two years become integrated into the service
delivery system for rural Victoria. The experience of the service in piloting and
integrating the use of videoconferencing to rural Victoria has been an important
development for child and adolescent mental health services in Australia.
PMID- 9640745
TI - Telemedicine applications in otolaryngology.
AB - A prospective study of the use of realtime and store-and-forward teleconsulting
was carried out in patients who presented to the New York Eye and Ear Infirmary
for otolaryngology care. Forty-five patients were seen in the study. There were
no significant differences between local and remote otolaryngologists when
interpreting the examinations, indicating that transmission did not affect the
ability of a qualified physician to make an accurate diagnosis. In the store-and
forward examinations only 62% of the electronic records provided sufficient
information for a confident diagnosis. Records were judged inadequate primarily
due to poor selection, or an insufficient number of stored images. The study
demonstrates that both interactive and store-and-forward techniques can be used
to provide accurate clinical consultations in nasopharyngolaryngoscopic
examinations. However, since store-and-forward consultations include less
information and do not provide immediate feedback, as well defined clinical
protocol for assembling the electronic consultation is needed.
PMID- 9640746
TI - The International Telecommunication Union's report on Telemedicine and Developing
Countries.
AB - This paper reviews some of the main conclusions and recommendations from the
Report on Telemedicine and Developing Countries, which was prepared for the
International Telecommunication Union (ITU). The report is the result of three
years' effort by a group of experts in telecommunications and telemedicine from
around the world. It provides an extensive survey of the telemedicine experience
of various countries. It discusses the different types and applications of
telemedicine, the technologies used, costs and benefits, trends, prospects for
global standards, and provides guidelines and recommendations to developing
countries for implementation of telemedicine services. The ITU study group which
prepared the report is expected to begin some new tasks in 1998, including the
identification of a set of pilot telemedicine projects for developing countries.
PMID- 9640747
TI - Design of mobile telemedicine systems using GSM and IS-54 cellular telephone
standards.
AB - This paper presents an overview of the design of mobile telemedical systems using
cellular telephone channels. A mobile telemedicine communication system was
studied using both the GSM and the IS-54 standards, which are the most widely
used commercial cellular telephone systems in Europe and North America,
respectively. A simulation using a photoplethesmography signal showed successful
transmission of data with bit error rates of less than 10(-7) at the receiver for
the IS-54 standard and less than 10(-5) for the GSM standard, depending on the
mobile channel conditions used.
PMID- 9640748
TI - A joint US-UK study of home telenursing.
AB - Nursing notes for patients nursed at home in the USA and the UK were reviewed
using an abstraction instrument developed and tested in the US. More than 1700
episodes of patient care at home were reviewed: 906 in the US and 839 in the UK.
Preliminary data suggest that in the US approximately 45% of home nursing visits
could be done via telemedicine, while the figure is lower in the UK, less than
15%. Pilot trials of an analogue video-telephone in Kansas City and Belfast
suggest that even relatively low-quality compressed video may be useful for home
nursing. Clearly, there are differences between the two countries which merit
further study, but there is evidence to suggest that telemedicine may have a role
in the delivery of home health care.
PMID- 9640749
TI - Feasibility of orthopaedic teleconsulting in a geriatric rehabilitation service.
AB - Fifteen elderly patients participated in a teleconsultation with an orthopaedic
surgeon, which was then followed by a conventional, face-to-face consultation.
The comparison between the surgeon's ratings for both types of consultation
suggested that the telemedicine consultation was satisfactory in terms of the
quality of image and sound, the clinical examination and general simplicity. The
telemedicine consultations did not generate a need for any additional clinical
investigations, although in two cases a face-to-face consultation was necessary
to clarify clinical signs (shortening of a limb and scar tissue). The surgeon's
rating of his decision level was superior in the face-to-face situation in four
cases, and for 11 patients it was equal. Similarly, the surgeon's level of
confidence in decision making was superior in the conventional situation for five
patients and equal for 10 patients. Patient attitudes towards teleconsulting were
favourable. There was a high level of patient satisfaction. Teleconsulting
between orthopaedic surgeons and elderly patients therefore appears to be
possible, provided that certain technical, clinical and psychological
considerations are addressed.
PMID- 9640750
TI - Continuous assessment of the risk of falling using telecare.
AB - The prevention of falls in the elderly could be based on risk assessment and the
prediction of when an individual is likely to sustain an injury. A telecare
system should allow the dynamic assessment of risk to be produced by a control
centre computer, based on data transmitted from local sensors in the elderly
person's home. A fall risk index could be calculated from mobility, activities of
daily living and medication. However, substantial data-sets will be required
before such fall risk indices attain statistical significance. As they are
developed, fall prediction algorithms could be constantly reviewed and modified
in order to reach the point where an acceptable level of accuracy is reached.
PMID- 9640751
TI - Benefits of using telemedicine and first results in Bosnia and Herzegovina.
AB - In October 1996 the Institute of Pathology with the Radiology and Ophthalmology
Clinic of the university hospital of Sarajevo joined the experimental
telemedicine project SHARED. Two months after the project began, dermatology,
paediatrics and haematology were also included. During the first phase we had 40
teleconsultations that showed us the benefits of using telemedicine. Our opinions
and the opinions of the pathologist in Milan were similar for most of the
biopsies (78%). The total time required for the consultation for the first 40
cases was 372 min, or 9.3 min each, on average. The longest consultation time was
25 min. The largest number of images was 44 per case, the smallest four. Because
of problems of infrastructure and lack of experts, telemedicine will be important
to a small country like Bosnia and Herzegovina.
PMID- 9640752
TI - Easy Medic: an Internet application for the general practitioner.
AB - A research project has been carried out to develop a client server application
which supplies the general practitioner (GP) with a 'personal digital assistant'
(hand-held mobile computer) to connect to Web servers at a hospital site through
the Internet. This allows the doctor to book medical examinations, hospital
admissions and manage patient data. The application used advanced object-oriented
techniques, on both the client and the server side. The connection to a Web
server was achieved through GSM wireless cellular telephones using standard
Internet protocols (HTTP, TCP/IP and CGI). Conventional telephone lines can be
used as well. Other application modules on the client side provided patients
medical record supervision, GP schedule management, general information about
hospitals and clinics, and pharmacy consultation. These services should help GPs
in their daily work. Moreover, the quality of health-care resource management and
cost supervision should improve, since each GP 'transaction' is automatically
entered in realtime into a database at the server. The services are under test in
the health-care system of an urban area in southern Italy.
PMID- 9640753
TI - The legal and ethical aspects of telemedicine.
AB - The medical challenge presented by telemedicine is for doctors to find
satisfactory ways of doing their jobs from a distance. The legal and ethical
challenge presented by telemedicine is to ensure that the very highest standards
are met from the outset. This can be achieved only by the legal and medical
professions learning to combine their expertise, rather than by the former
adopting the adversarial stance that has come to punctuate its relationship with
the latter in recent years.
PMID- 9640754
TI - The use of telemedicine to treat ophthalmological emergencies in rural Australia.
AB - A retrospective analysis was made of a cohort of patients who presented
sequentially with acute ophthalmological conditions which were managed by
telemedicine consultation. Twenty-four patients presented with acute problems
requiring specialist ophthalmological advice to the emergency department of a
remote hospital in Mt Isa, Queensland, between December 1996 and February 1997.
Tele-ophthalmology consultations were carried out with three ophthalmologists
working in a specialist eye clinic in Townsville, 900 km away. Patients and
doctors were extremely positive about the telemedicine facility. Tele
ophthalmology was an effective means of providing acute specialist consultation
in a remote emergency department. By reducing the need for acute transfers to the
tertiary hospital in Townsville, significant benefits can be anticipated--both
financial and in terms of convenience for the patient. Benefits for medical staff
in skills acquisition and education were also evident.
PMID- 9640755
TI - A survey of physicians' acceptance of telemedicine.
AB - Physicians' acceptance of telemedicine is an important managerial issue facing
health-care organizations that have adopted, or are about to adopt, telemedicine.
Most previous investigations of the acceptance of telemedicine have lacked
theoretical foundation and been of limited scope. We examined technology
acceptance and usage among physicians and specialists from 49 clinical
departments at eight public tertiary hospitals in Hong Kong. Out of the 1021
questionnaires distributed, 310 were completed and returned, a 30% response rate.
The preliminary findings suggested that use of telemedicine among clinicians in
Hong Kong was moderate. While 18% of the respondents were using some form of
telemedicine for patient care and management, it accounted for only 6.3% of the
services provided. The intensity of their technology usage was also low,
accounting for only 6.8% of a typical telemedicine-assisted service. These
preliminary findings have managerial implications.
PMID- 9640756
TI - [Effects of coca chewing on the glucose tolerance test].
AB - The effects of coca chewing on the glucose tolerance test were measured. The
subjects were 14 habitual coca chewers and 14 non-chewers. All were of Aymara
ancestry and came from a rural community from the "Altiplano" close to the city
of La Paz. The coca users chewed coca leaves during 3 1/2 hours of the test. The
non-chewers showed a significant hypoglycemia at 120 minutes of the test. This
effect was not observed in the coca chewers. The hormonal counter-regulation
response to hypoglycemia worked perfectly in non-chewers, since glucose levels
reached normal values at 180 minutes of the test. These results suggest that coca
chewers, at high altitude do not present hypoglycemia, due to an antagonic action
of coca metabolites on insulin; allowing a greater availability of glucose in the
organism. This would have a positive effect on metabolism in an environment of
hypobaric hypoxia, known to lead to situations of hypoglycemia.
PMID- 9640757
TI - Medical informatics in perinatology project AGUSTINA in Argentina.
AB - This paper reviews the development of the field of medical informatics in Latin
America. It also describes the preliminary results of a computer-based data
management system, named AGUSTINA, which is comprised of maternal and infant data
on 6195 deliveries that occurred between June 1990 and December 1995 in a
hospital in the surroundings of Buenos Aires, Argentina. These data were
fundamental for the instrumentation of preventive community-oriented activities
in the area. Finally, this paper describes recommendations for future actions in
the area of medical informatics in Latin America.
PMID- 9640758
TI - Lower motor neuron syndrome associated with anti-GM1 antibodies.
AB - It has been recently recognized that increased titers of serum anti-GM1
antibodies may be associated with motoneurone diseases or with multiple motor
neuropathy with or without conduction block and also with chronic sensorimotor
neuropathy and Guillain-Barre syndrome. Santoro et al. were the first to note
that anti-GM1 antibodies were able to bind to the nodes of Ranvier of the sural
nerve of a patient with clinical signs and symptoms mostly resembling amyotrophic
lateral sclerosis who also showed, in nerve conduction studies, multifocal motor
nerve fibers conduction block and serum IGM anti-GM1 antibodies. The two patients
presented in this report had asymetrical motor neurone disease with signs and
symptoms of lower motoneurone involvement, and other signs, in the first patient,
which suggested the existence of upper motoneurone damage. Besides, the second
patient also had clinical sensory impairment in the lower limbs.
Electrophysiologically, none of them had nerve conduction block but both showed
inexcitable median and sural nerve sensory fibers. Both had high titers of anti
GM1. A sural biopsy of both patients showed immunoglobulins into the sensory
fibers. However, we do not know whether the anti-GM1 antibodies bind to a cross
reactive glycolipid other than the GM1 itself. In any case, it seems that the
presence of anti-GM1 antibodies might be a marker signalling a potentially
treatable immune disorder which may have signs of lower and upper motor neurone
disease and, also, clinical and electrophysiological evidences of peripheral
sensory involvement.
PMID- 9640759
TI - [Changes in the levels of delta-aminolevulinic acid dehydratase in chronic
alcoholic patients].
AB - Medical and biochemical analysis were performed on 58 patients with chronic
alcoholism. In accordance with medical characterisation, patients were divided in
three groups: A (patients having only hepatopathy), B (patients with hepatopathy
and neuropathy) and C (patients having only alcoholic neuropathy).
Simultaneously, several parameters related to heme biosynthesis were examined.
Urinary delta-aminolevulic acid (ALA), porphobilinogen (PBG) and porphyrins and
fecal porphyrins measurements did not show significant difference among all
studied groups. The activities of ALA-dehydratase (ALA-D), uroporphyrinogen-I
synthase (URO-I-S) and uroporphyrinogen-III-synthase (URO-III-S) were monitored
in peripheral erythrocytes. From the enzymes measured, only ALA-D levels in
groups B and C were significantly depressed (p < 0.002) compared with normal
subjects. The decrease in ALA-D correlated with the degree of neuropathy.
PMID- 9640760
TI - [Community-acquired Staphylococcus aureus bacteremia in children: analysis of
mortality risk factors].
AB - Sixty episodes of community-acquired Staphylococcus aureus bacteremia (SaCB) were
prospectively analyzed between January 1990 and December 1994. The mean age of
the patients was 78 (1-180) months. Thirteen (55%) of the children had underlying
disease, the most frequent one being acute lymphoblastic leukemia. In 83% of the
episodes a primary site of infection was observed. Skin and osteoarticular foci
were the most frequently encountered. Only two patients had endocarditis.
Arterial hypotension was detected in 17% of the patients. Ninety two percent of
S. aureus isolated were penicillin-resistant. Only two strains were methicillin
resistant. In 24 (40%) episodes where metastatic foci were detected,
osteoarticular infections were predominant. Mortality due to SaCB was 20%.
Multivariate analysis by logistic regression revealed that arterial hypotension
(RR = 24.8; 4.77-128.9), leucopenia (RR = 10.3; 1.25-86.2) and non hemato
oncologic diseases (RR = 10.0; 1.09-92.2) correlated with high mortality rate (p
= < 0.001).
PMID- 9640762
TI - [Anti-neutrophil cytoplasmic antibodies (ANCA) in patients with symptomatic and
asymptomatic HIV infection].
AB - The cytopathic effect of HIV on CD4 T cells, as well as the active autoimmune
mechanism occurring during infection, have been documented. Of the cytokines
involved in the pathogenesis of AIDS, the main one produced by the monocyte
macrophage series is tumor necrosis factor alfa (TNF alpha). This cytokine
induces antigens such as proteinase 3 (Pr 3) or mieloperoxidase (MPO). Anti
neutrophil cytoplasmic antibodies (ANCA) are directed against this type of PMN
antigens. In the present paper, the role of anti-neutrophil cytoplasmic
antibodies (ANCA) in HIV infected patients as responsible for autoimmune
phenomena in relation to opportunistic infections, was studied. A total of 88
serum samples belonging to 49 asymptomatic and 39 symptomatic HIV infected
patients were tested for ANCA by an indirect immunofluorescence (IIF) test over a
neutrophil substrate. ANCA were detected in 53.8% of symptomatic patients as
compared to 4.1% in asymptomatic cases (p < 0.0001). A 95.9% correlation was
observed between ANCA-positive samples and pulmonary infection (n = 20). In those
ANCA (+) samples 95.9% correlation was found with pulmonary infection (n = 20).
Pulmonary infection due to Mycobacterium tuberculosis is a frequent finding in
HIV infected patients from Northeastern Argentina. When the presence of ANCA in
TB(+) HIV(+) and TB(+) HIV(-) patients was studied, it was seen that positive
ANCA significantly correlated with the first group (p < 0.001). The presence of
ANCA was not related to viral infections, toxoplasmosis, neurological features of
AIDS, vasculitis or malignant diseases. ANCA during pulmonary infection, mostly
caused by TB, as well as PMN infiltration in pulmonary parenchyma, and the
deregulated immune reaction elicited by HIV, may contribute to the onset of
autoimmune phenomena. The presence of human T lymphocytes reactive to heat stress
proteins (Hsp), an important target of immune response against certain
intracellular auto-antigens such as MPO from PMN, added to the mechanism of
molecular mimicry, could explain the association of ANCA and TB in patients with
severe alterations of their immune response. According to these results, the
limited presence of ANCA in asymptomatic patients HIV(+) and in HIV(-) with
pulmonar TB, could indicate that the virus may not be responsible for the
induction of these antibodies.
PMID- 9640761
TI - [Prevalence of hepatitis C antibodies in plasma donors for the treatment of
Argentine hemorrhagic fever].
AB - For Argentine Hemorrhagic Fever, a disease caused by Junin virus (JV), there is
an effective treatment, consisting of the transfusion of immune plasma (IP). This
plasma is obtained from individuals who have had the disease. Since Hepatitis C
virus (HCV) is transmitted parenterally, this study was aimed to estimate the
prevalence of anti-HCV in a population of IP donors. In this study, 376 donors
(47 females and 329 males) were studied: 95 individuals (24 females and 71 males)
who had had FHA but had not received treatment and 88 laboratory workers (57
females and 31 males) who were included as controls. Serum samples were tested by
EIA (Abbott, Germany) for HCV, and later confirmed by LIATEK (Organon, Ireland).
Antibodies to HCV were detected in 29/376 donors (7.7%), in only 1/95 (1.0%)
untreated convalescents of AHF and in 1/ 88 (1.1%) of laboratory workers.
Retrospective analysis of the seroconversion for HCV in these individuals
demonstrated that in 16/24 donors (66.6%) the infection by HCV was probably
associated with the IP transfusion. The data presented herein show how the
infection with HCV was disseminated among donors of IP, stressing the risk
associated to transfusional practices, and emphasizing the need of vaccination to
prevent AHF and also the risk inherent to its treatment.
PMID- 9640763
TI - [In vitro study of hemopoietic progenitors in human umbilical cord blood treated
with different cytokines and autologous serum].
AB - The aim was to obtain the ex vivo expansion of human umbilical cord blood (HUCB)
cells. A total of 19 samples were assayed to evaluate the number and type of
hemopoietic progenitor cells, their proliferating capacity and the stimulating
potency of cord blood serum. METHODS: a) CFU-GM, CFU-GEMM and BFU-E cultures in
the presence of CSF, BM serum or HUCB serum; b) 35 day LTC in liquid media
whether in presence of IL-3 + GM-CSF + SCF or autologous serum (AS). Cells were
demidepopulated at 7-day intervals and fresh medium and cytokines were added.
Harvested cells were cultured in bone marrow (BM)/ SM and colonies were evaluated
after 10 days. RESULTS: The mean number of CFU-GM was similar to BM values; the
maximum number of colonies was observed at day 7 and remained high until day 21
whether in addition of cytokines or AS. A total of 8 samples gave rise to
colonies up to day 35; these samples showed higher values than BM in SM; HUCB
serum has a great stimulating effect on BM cells and HUCB cells compared with
nonspecific stimulating factors; moreover, HUCB showed a large dispersion.
CONCLUSION: 1) HUCB contains a high number of hemopoietic progenitor cells with a
large dispersion coefficient, 2) HUCB plasma has a great stimulatory capacity, 3)
it is possible to induce the expansion of HUCB progenitors in LTC either in the
presence of cytokines or of AS without loss of potency.
PMID- 9640764
TI - [Essential fatty acids of the n-6 and n-3 series supplied to human diet by edible
fish from the Parana river].
AB - The fatty acid composition of muscle lipids from eadible fish from Parana river
such as Dorado (Salminus maxillosus), Boga (Leporinus affinis), Pati
(Luciopimelodus pati) and Surubi (Pseudoplatistoma coruscans) was studied in
order to determine their food value in relation to essential fatty acid n-3 and n
6 supply. Flesh from these fishes is relatively lean and its lipids only contain
35% to 38% saturated fatty acids. Significant amounts of n-6 polyethylenic acids,
mainly linoleic, arachidonic and the n-3 acids, docosahexaenoic,
docosapentaenoic, eicosapentaenoic and alpha-linolenic are found in these fishes.
Pati flesh is the most abundant in n-6 acids with a value of 306 mg/100 g muscle,
followed by Boga, Dorado and Surubi. A large proportion of n-3 acids is supplied
by muscles of Dorado, 183 mg/100g muscle, followed by Pati, Boga and Surubi. More
than 90% of the lipids that supply these acids are present in triacylglycerols in
Dorado, Boga and Pati. In Surubi, triacylglycerols constitute 60% and the
remaining lipids are phospholipids. Cholesterol content in flesh of fresh water
fish was analyzed, and it did not exceed 4.7 micrograms/g muscle for Pati, being
lower for the other species studied. Fish considered in this work represent a
good dietary source of polyunsaturated fatty acids either n-6 or n-3 series for
the mediterranean population in our country.
PMID- 9640765
TI - [Action of liver extract from partially hepatectomized mice on the mitotic
activity of young mouse enterocytes].
AB - We have previously demonstrated that adult mouse plasma obtained 36 hours post
partial hepatectomy has an inhibitory effect on the mitotic activity of
enterocytes from young mouse duodenal cripts. In this paper we investigate
whether this effect is derived from any regenerating liver factor. Accordingly,
we studied the action of adult mouse (90 days old) liver extract obtained 36
hours after partial hepatectomy (70%), on the mitotic activity of young mouse
enterocytes, considering 3 cellular levels of the duodenum cripts. Thirty six
C3H/S inbred female mice (27 days old) were employed. Half of them received at
16:00 hour an intraperitoneal injection of saline and the other half received
liver extract (0.01 ml/g). Animals from each group were sacrificed at 08:00/ 16,
12:00/20 and 16:00/24 (time of day/hours post treatment). All the animals
received an intraperitoneal dose of colchicine (2 micrograms/g) 4 hours before
sacrifice. The results are expressed as colchicine metaphases/1000 nuclei and
show that the mitotic activity is significantly lower in the animals treated with
the extract than in the controls. This inhibiting effect is observed at the
levels from 1 to 4 and from 5 to 12 cells of the analyzed cripts. At the
superficial level from 13 to 20 cells there is no modification of the
proliferative activity. This inhibiting effect on the mitotic activity of
duodenum enterocytes from the basal and intermedial zone of the cripts is
probably due to a liver diffusing factor.
PMID- 9640766
TI - [Cardiac failure secondary to hypoparathyroidism. An unusual presentation].
AB - The case of a 37 year old woman with hypoparathyroid congestive heart failure
(CHF) is reported. Thyroidectomy had been performed eight years earlier and she
had experienced symptoms of hypocalcemia postoperatively. CHF improved rapidly
and completely with the treatment of hypocalcemia. Good prognosis is emphasized
but it is necessary to think about this cause of ventricular dysfunction in a
patient with CHF and a history of neck surgery in order to make an early
diagnosis. Pathogenic mechanisms and differential diagnosis are discussed.
PMID- 9640767
TI - [Large granular lymphocytic leukemia. Case report with scarce expression in
peripheral blood].
AB - The case of a 33 year old woman with a large granular lymphocytic leukemia is
presented. The main symptoms were neutropenia and recurrent respiratory bacterial
infections. No enlargement of the liver, spleen or lymph nodes was noted.
Circulating lymphocytes averaged 3000/microliter with 35% of large granular
cells. The bone marrow biopsy showed lymphatic infiltration with both nodular and
interstitial pattern. Lymphocytes bore the T suppressor phenotype (CD8+, CD45
RO+, CD20-, kappa-, lambda-). Cytogenetic studies revealed a low expression clone
with 7q-: del (7)(q36). Gene rearrangements for immunoglobulins or T-cell
receptors could not be demonstrated by Southern Blot. Bone marrow cultures grew
normally while both normal and patient bone marrow showed marked inhibition when
incubated with patients serum. Normalization of the peripheral granulocytic count
was obtained with prednisone, while granulocytic-stimulating factors,
chlorambucil, and cyclosporine A were partially active or inactive. We suggest
that this case represents a form of the lymphoproliferative disease of granular
lymphocytes. To our knowledge, the deletion of the long arm of chromosome 7 has
not been described in this disease.
PMID- 9640768
TI - [Superantigens and retroviral infections. Increase of mammary tumorigenicity due
to recombination between exogenous and endogenous MMTV viruses].
AB - A number of milk-borne exogenous mouse mammary tumor viruses (MMTV) infect mice
shortly after birth and, when expressed, produce superantigens. Herein we
describe the biological effects of new variants of exogenous MMTV: one of them
(BALB14) present in BALB/c mice and showing a low ability to induce mammary
tumors, and the other (MMTV-7) being the result of recombination between the
BALB14 and the Mtv-7 endogenous provirus. The recombinant virus which has the SAg
specificity of Mtv-7 was amplified in BALB/c mice this fact correlating with a
high incidence of mammary tumors. The role of strong SAgs in the mechanism by
which the recombinant virus increases its title in a susceptible host is
discussed. The results obtained suggest that the presence of non-productive
endogenous proviruses--considered as conferring a selective advantage to the
mouse population by protecting it from infection with exogenous MMTV--should also
be advantageous to the pathogen by increasing its variability, thus broadening
the host range and allowing the expansion of highly tumorigenic variants.
PMID- 9640769
TI - [Role of different forms of fibronectin in in vitro bovine follicular
development].
AB - This study was aimed at testing the hypothesis that different forms of
fibronectin (FN), produced as a consequence of the alternative splicing of the
precursor mRNA, play specific roles during follicular development. In particular,
we analyzed the presence of the ED-I region, which is absent in the plasma form.
Analysis of FN levels in follicular fluids corresponding to different stages of
development of bovine follicles revealed marked changes in the concentrations of
ED-I + FN whereas total FN levels remained relatively constant. A negative
correlation (P < 0.001) was detected between ED-I + FN and estradiol levels. This
steroid was without effect on the alternative splicing of FN in primary cultures
of bovine granulosa cells. However, cAMP produced a marked decrease in the
incorporation of the ED-I region. In contrast, transforming growth factor beta
(TGF-beta) elicited both a stimulation on overall FN synthesis and an increase in
the inclusion of ED-I. This effect was evident at the protein level (Western
blots) and also in the mRNAs (Northern blots). A peptide corresponding to the ED
I region stimulated DNA synthesis in a bovine granulosa cell line (BGC-1) whereas
the peptide corresponding to the flanking sequences was without effect. Data
presented herein suggest a novel form of regulation by which changes in the
primary structure of FN may mediate some of the effects of gonadotropin and
intraovarian factors during follicular development.
PMID- 9640770
TI - [Regulation of testicular steroidogenesis by nitric oxide].
AB - Testicular macrophages as well as endothelial cells, which are intimately
associated with Leydig cells, constitute a potential source of paracrine nitric
oxide (NO). In the present study, we investigated the effect of NO donors on MA
10 murine Leydig tumor cell line and rat Leydig cell steroidogenesis. We observed
that NO donors, reversibly inhibit hCG-induced steroidogenesis in both types of
cells. We also studied NO mechanism of action. Contrary to what is observed in
many other systems, NO inhibitory effect on Leydig cell steroidogenesis is not
mediated by cGMP, as NO fails to increase cGMP production and cGMP analogs do not
reproduce NO effect. NO does not modify the production of cAMP, the main second
messenger that mediates gonadotropin action. When we studied NO effect over the
steroidogenic pathway in MA-10 cells, we found that NO is inhibiting the
conversion of cholesterol to pregnenolone. Taken together these results show an
inhibitory effect of NO donors on Leydig cell steroidogenesis and suggest that NO
can be directly inhibiting cholesterol side-chain cleavage enzyme (cytochrome P
450 scc) as it does with other heme proteins, including different cytochromes P
450.
PMID- 9640771
TI - [Community-acquired pneumonia in adults. Clinical practice guideline for
Argentina. Study Group on Community Acquired Pneumonia].
AB - Community-acquired pneumonia (CAP) affects approximately 1% of the population
annually. Initial antimicrobial therapy is most often empirical. Guidelines
designed in other countries for the empirical management of CAP are not
recommended for use in Argentina. Studies from other countries were considered
together with unpublished local data to define the potential etiologic
microorganisms and their antimicrobial susceptibility. Recommended diagnostic
tests, groups of patients for different therapies and hospitalization criteria
were defined. Severe CAP requiring intensive care was distinguished from the rest
because of its distinct spectrum of etiologic agents and its high mortality,
requiring a more focused therapy. Age, coexisting conditions and severity of
illness were taken into account in the election of therapy.
PMID- 9640772
TI - [Heart failure and dysautonomia in a hemodialyzed patient].
PMID- 9640773
TI - [Kaposi sarcoma after renal transplantation].
PMID- 9640774
TI - [Nuclear transfer and cloning].
PMID- 9640775
TI - [Thymectomy and myasthenia gravis].
PMID- 9640776
TI - [Exercise and sudden death. Is it possible to prevent it?].
PMID- 9640777
TI - [Acute effect of lorazepam on respiratory muscles in patients with chronic
obstructive pulmonary disease].
PMID- 9640778
TI - [Exogenous gangliosides and Guillain-Barre syndrome].
PMID- 9640779
TI - Genomic characterization of adenovirus serotype 7 isolated in Brazil from acute
respiratory disease patients during the period from 1980 to 1991.
AB - Forty isolates of adenovirus type 7 were analized by restriction enzyme digestion
with BamHI, SmaI, EcoRI and HindIII. These isolates were obtained from acute
respiratory disease patients during the years 1980 to 1991. Only two genomic
types were found: Ad7b and Ad7e, with Ad7b (87.5%) being more frequent than Ad7e
(12.5%). The genomic type Ad7e appeared in the years 1980, 1981 and 1983. Ad7b
appeared in 1982 and it was the only genomic type found from 1984 to 1991. Both
genomic types were responsible for lower (LRTI) and upper (URTI) respiratory
tract infection, but the proportion LRTI/URTI is higher for Ad7b (25/6) than for
Ad7e (1/4).
PMID- 9640780
TI - Hantavirus pulmonary syndrome in the Province of Rio Negro, Argentina, 1993-1996.
AB - Early in 1995 the first case of Hantavirus Pulmonary Syndrome was serologically
confirmed in El Bolson (Province of Rio Negro, Argentina), corresponding to the
third outbreak reported in Argentina. A total of 26 cases of HPS related to the
Andean region of Rio Negro Province, were reported from 1993 to 1996, 17 in El
Bolson, 4 in San Carlos de Bariloche, and 5 in Buenos Aires. The incidence rate
was 5.03 x 100,000 with a mortality rate of 51.85 x 100. The occurrence of cases
was mainly seasonal, with a significantly greater number in the spring, and the
persons affected mainly lived in urban or periurban areas. In four cases, the
affected individuals were members of a couple, spouses or live-in contacts. Seven
cases were Health workers (physicians, nurses or administrative staff). Twelve
cases were related among them, due to an outbreak of 80 days. Two of them did not
visit the Andean region. A total of 139 rodents were captured and seven of them,
Olygoryzomys longicaudatus, were found to be serologically positive. The
possibility of infection by contact with rodents or fecal matter is being
analyzed and also hypothesis related with interhuman transmission.
PMID- 9640781
TI - Quantification of the population and phagocytary activity of hemocytes of
resistant and susceptible strains of Biomphalaria glabrata and Biomphalaria
tenagophila infected with Schistosoma mansoni.
AB - Among the determinant factors in the resistance and susceptibility of
Biomphalaria to Schistosoma mansoni, hemocytes play an important role. Aiming at
studying S. mansoni/Biomphalaria interactions related to hemocytes, the first
step is certainly connected with the standardization of this cell population in
uninfected Biomphalaria. In this way, quantification of this cell population in
hemolymph, as well as its phagocitary capacity, have been determined for the
first time. Furthermore, using susceptible and resistant strains of B. glabrata
and B. tenagophila, the hemocytegram and phagocytary capacity of hemocytes after
infection with S. mansoni were determined too. Resistant and susceptible strains
of B. glabrata (BA and BH, respectively), as well as resistant and susceptible
strains of B. tenagophila (TAIM and CF, respectively) were infected with 10
miracidia of the LE and SJ strains of S. mansoni, respectively. These infected
snails and respective uninfected controls were assessed in relation to the number
of circulating hemocytes and alteration in the phagocytary capacity, by using
Zymozan and MTT. Reading was taken by means of a spectrophotometer at 5 hours and
1, 2, 5, 10, 20 and 30 days after infection. The results showed a decrease in
population of the circulating phagocytary cells, 5 hours after infection. One day
post-infection, the circulating cells of the susceptible snails showed an
increased metabolic activity, but the same event could not be observed in the
resistant strains. In the subsequent observation periods, significant differences
among the strains studied could not be observed until the end of the experiment.
PMID- 9640782
TI - Differentiation of pathogenic and non-pathogenic leptospires by means of the
polymerase chain reaction.
AB - A polymerase chain reaction was carried out to detect pathogenic leptospires
isolated from animals and humans in Argentina. A double set of primers (G1/G2,
B64-I/B64-II), described before, were used to amplify by PCR a DNA fragment from
serogroups belonging to Leptospira interrogans but did not allow to detect
saprophytic strains isolated from soil and water (L. biflexa). This fact
represents an advantage since it makes possible the differentiation of pathogenic
from non-pathogenic leptospires in cultures. The sensitivity of this assay has
been determined, allowing to detect just only 10 leptospires in the reaction
tube. Those sets of primers generated either a 285 bp or 360 bp fragment,
depending on the pathogenic strain.
PMID- 9640783
TI - Peptic disease and Helicobacter pylori are highly prevalent in patients with the
indeterminate form of Chagas' disease: report of 21 cases.
AB - Given that chagasic patients in the indeterminate form of this disease, can have
abnormal motility of the digestive tract and immunologic abnormalities, we
decided to assess the frequency of peptic disease and Helicobacter pylori (Hp)
infection in these individuals. Twenty-one individuals, 13 males and 8 females,
mean age 37.6 +/- 11.1 years, were examined. Biopsies of the duodenum, antrum,
lesser and greater gastric curvature and esophagus were performed. The endoscopic
findings were of chronic gastritis in 20 (95.2%) patients, duodenal ulcer in 3
(14.3%), gastric and duodenal ulcer in 3 (14.3%), gastric ulcer alone in 1
(4.8%), esophagitis in 5 (23.8%), and duodenitis in 5 (23.8%). The diagnosis of
infection by the Hp was done by the urease test and histologic examination. Hp
infection was found in 20 (95.2%) individuals: in 20 out of them in the antrum,
in 17 in the lesser curvature, and in 17 in the greater curvature. Hp was not
found in the esophagus and duodenum. The only individual with no evidence of
infection by Hp was also the only one with normal endoscopic and histologic
examinations. The histologic examinations confirmed the diagnoses of gastric
ulcer as peptic, chronic gastritis in 20 patients, duodenitis in 14, and
esophagitis in 9. In this series the patients had a high frequency of peptic
disease, which was closely associated with Hp infection.
PMID- 9640784
TI - Prevalence of HTLV-I and HTLV-II infections among HIV-1-infected asymptomatic
individuals in Sao Paulo, Brazil.
AB - Human immunodeficiency virus (HIV-1)-infected subjects with acquired
immunodeficiency syndrome (AIDS) are often infected with multiple pathogens. In
particular, HTLV-I and HTLV-II infections have been found more frequently in AIDS
patients than in asymptomatic individuals in Europe and Japan. We carried out a
serosurvey among asymptomatic HIV-1-infected subjects in Sao Paulo, Brazil and
compared our results with those of other investigators. In this study, we found
HTLV infection in 1.5% of 266 asymptomatic and 14% of 28 AIDS patients.
Epidemiological data obtained from patients pointed out the use of intravenous
drugs as the principal risk factor for acquiring retroviruses. In conclusion, our
results are in accordance with other studies done in Brazil and elsewhere where
the principal risk group for HIV/HTLV-I/II coinfection was IDU.
PMID- 9640785
TI - Agreement between premortem and postmortem diagnoses in patients with acquired
immunodeficiency syndrome observed at a Brazilian teaching hospital.
AB - Acquired immunodeficiency syndrome (AIDS) is one of the main causes of death in
adults worldwide. More commonly than in the general population, in patients with
AIDS there is substantial disagreement between causes of death which are
clinically suspected and those established by postmortem examination. The
findings of 52 postmortem examinations were compared to the premortem (clinical)
diagnoses, and there was 46% agreement between them. Fifty two percent of the
patients had more than one postmortem diagnosis, and 48% had at least one AIDS
related disease not suspected clinically. Cytomegalovirus infection was the
commonest (30.7%) autopsy finding, but not a single case had been suspected
premortem. Bacterial infection, tuberculosis, and histoplasmosis were also
common, sometimes not previously suspected, postmortem findings. This study shows
that multiple infections occur simultaneously in AIDS patients, and that many
among them are never suspected before the postmortem examination. These findings
suggest that an aggressive investigation of infections and cancers should be done
in patients with AIDS, particularly in those who do not respond to therapy of an
already recognized condition.
PMID- 9640786
TI - Amastigotes forms of Trypanosoma cruzi detected in a renal allograft.
AB - Trypanosoma cruzi, the causative agent of Chagas' disease assumes two distinct
forms in vertebrate hosts: circulating trypomastigote and tissular amastigote.
This latter form infects predominantly the myocardium, smooth and skeletal
muscle, and central nervous system. The present work describes for the first time
the detection of amastigote forms of T. cruzi in the renal parenchyma of a kidney
graft recipient one month after transplantation. The patient was serologically
negative for Chagas' disease and received no blood transfusion prior to
transplant. The cadaver donor was from an endemic area for Chagas' disease. The
recipient developed the acute form of the disease with detection of amastigote
forms of T. cruzi in the renal allograft biopsy and circulating trypomastigote
forms. The present report demonstrates that T. cruzi can infect the renal
parenchyma. This mode of transmission warrants in endemic areas of Chagas'
disease.
PMID- 9640787
TI - Subcutaneous scedosporiosis. Report of two cases and review of the literature.
AB - Two cases of subcutaneous scedosporiosis, caused by Scedosporium apiospermum, are
reported. Both patients had lesions localized in the forearm: a solitary
ulceration in one and a sporotrichoid-like lesion in the other. The literature is
reviewed.
PMID- 9640788
TI - Hantavirus pulmonary syndrome. Report of the first three cases in Sao Paulo,
Brazil.
AB - The hantavirus pulmonary syndrome was first recognized in cases that occurred in
the U.S. in 1993, which served as an alert not only for American physicians but
also for physicians in other countries for the identification of the disease. In
the city of Sao Paulo, Brazil, 3 cases of the syndrome were recorded in 1993. The
patients were young brothers residing in the Mata Atlantica (Atlantic Forest)
region submitted to recent deforestation. Two of the patients died of acute
respiratory insufficiency and the third recovered without sequelae. In the
surviving patient the diagnosis was established by a laboratory criterion based
on the detection of specific IgM and IgG class antibodies by indirect
immunofluorescence. In the two patients who died, the diagnosis was confirmed by
laboratory tests using immunoperoxidase technique for hantavirus in tissue, in
histological lung and heart sections in one case, and by clinical and
epidemiological data in the other.
PMID- 9640789
TI - DOT-enzyme-linked immunosorbent assay (DOT-ELISA) for evaluating IgG antibody
avidity in toxoplasmosis.
PMID- 9640790
TI - Hantavirus pulmonary syndrome in the rural area of Juquitiba, Sao Paulo
metropolitan area, Brazil.
PMID- 9640791
TI - How can Brazil's post-graduation courses in clinical areas be improved?
PMID- 9640792
TI - Clinical and radiological postoperative evaluation of posterior sagittal
anorectoplasty in patients with upper and intermediate anorectal malformations.
AB - The PSARP is today the most-used surgical technique for correction of high and
intermediary anorectal malformations. There is much controversy in the literature
about the post-operative evaluation of these cases. We studied 27 cases of
anorectal malformations from clinical and radiological aspects, in order to
analyse: 1. Fecal continence 2. Relationship between post-operative fecal
continence and the associated sacral anomalies 3. Relationship between the
radiological evaluation by defecogram and fecal continence From the analysis of
the cases, we concluded: 1. Fecal continence was achieved in 48.14% of the cases;
partial continence in 25.92%; and fecal incontinence in 25.92% of the cases. 2.
The presence of fecal incontinence was directly related to the associated sacral
anomalies.
PMID- 9640793
TI - A pioneering experience in Brazil: the creation of a center for assistance and
research for medical residents (NAPREME) at the Escola Paulista de Medicina,
Federal University of Sao Paulo.
AB - The decision to develop a treatment service for medical residents at Escola
Paulista de Medicina was influenced by three main factors: the suicide of four
young doctors (2 residents) at this institution between 1995 and 1996, a research
study that investigated stress among medical residents and the experience of
other countries in response to similar problems. NAPREME has the following
objectives: to help to reduce stress among residents, stimulate professional and
personal development, prevent professional dysfunction and emotional disorders,
offer psychological treatment, assess the tutors of residency programmes and
develop research programmes to better identify risk factors for emotional
problems during the residency period. We hope that by doing this the overall
quality of the residency programme will improve, both for the professionals and
the patients.
PMID- 9640794
TI - Hemorrhagic and thrombotic complications in patients with myeloproliferative
diseases.
AB - OBJECTIVE: To correlate the incidence of hemorrhage and thrombosis to bleeding
time (BT) and platelet aggregation in 27 consecutive patients with
myeloproliferative diseases (MPD). DESIGN: Retrospective study. SETTING: Public
tertiary referral center. PATIENTS: Eighteen patients with chronic myelogenous
leukemia (CML), 5 with polycytemia vera (PV), 2 with essential thrombocytemia
(ET) and 2 with idiopathic myelofibrosis (MF). Duke's BT and epinephrine-induced
platelet aggregation were performed on the patients and on 10 healthy
individuals. RESULTS: Eleven patients presented symptoms (41%):9 with hemorrhage
(33%) and 5 with thrombosis (19%). There were less symptomatic patients in the
CML group (28%) than in the other MPD (67%), without statistical significance
(Fisher, p = 0.06). Duke's BT was longer in symptomatic patients (Mann-Whitney, p
< 0.05). Platelet aggregation was abnormal in 7 patients (26%) and 71% of them
were symptomatic (Fisher, p = 0.07). CONCLUSIONS: The high incidence of bleeding
and thrombosis in patients with MPD was related to prolonged BT, but not to
platelet aggregation abnormalities.
PMID- 9640795
TI - Influence of body composition on the bone mass of postmenopausal women.
AB - AIMS: To investigate the influence of body weight (BW), fat mass (FM) and lean
mass (LM) on the bone mineral density (BMD) of several areas of the skeleton.
PARTICIPANTS: Sixty one white postmenopausal women (50.1 +/- 4.8 years).
MEASUREMENTS: Measurement of BMD by dual energy x-ray absorptiometry. The results
were analyzed by linear regression and the slopes of each curve were compared.
RESULTS: The results showed that the correlations between BW, FM and LM to BMD
were positive, whilst the correlations between age and years since menopause to
BMD were negative. LM was the main factor that influence BMD in almost all areas.
CONCLUSIONS: FM and LM present a positive effect on BMD, although LM is the main
determinant of bone mass. Moreover, higher values of LM and FM present a
protective effect against the reduction of BMD combined with menopause. Therefore
postmenopausal women with low BW, especially low LM, present serious risk for
developing osteoporosis.
PMID- 9640796
TI - CEA as a prognostic index in colorectal cancer.
AB - INTRODUCTION: The carcinoembryonic antigen, CEA, is the tumor marker most used in
colorectal patients, principally during follow up after radical surgery. High
serum CEA level before surgery is often associated with worse prognosis, in some
studies. OBJECTIVE: The purpose of this study was to evaluate the preoperative
carcinoembryonic antigen levels (CEA) and the frequency of recurrence. MATERIAL
AND METHODS: Eighty-three patients with colorectal cancer at Dukes stages A, B or
C were evaluated retrospectively. The patients follow up was at least two years
or to death. CEA was determined in serum by enzyme immunoassay (Sorin Biomedica),
normal value 0.5ng/ml. RESULTS: Disease recurrence was observed in 32 patients
(38.5%), 13 Dukes B and 19 Dukes C. Seventy five per cent of the patients with
CEA higher than 10ng/ml relapsed and 80% of the patients without recurrence had
normal CEA. Disease recurrence in patients with preoperative elevated CEA
occurred during the first year of follow up in 56% of the patients. CONCLUSION:
Although the tumor stage is today the most valuable prognostic variable in
colorectal cancer, the preoperative CEA value can provide some additional
information in the prognosis of the patient.
PMID- 9640797
TI - Uncommon allele in apo AI-CIII-AIV gene cluster in a family with congenital
generalized lipodystrophy.
AB - Congenital generalized lipodystrophy is a rare inherited disease. One of its
features is a disturbance in lipid metabolism characterized by
hypercholesterolemia and hypertriglyceridemia. A brother and a sister with
congenital generalized lipodystrophy, an 8-year old male and a 12-year old female
were studied. The mother and a 6-year old brother were healthy. The genetic
analysis of Sstl RFLP of the apo AI-CIII-AIV gene cluster showed the presence of
the rare Sstl allele (S2) in the patients but not in the healthy mother and
brother. As this uncommon allele has been reported to be related to high plasma
triglyceride levels, this association could be relevant in explaining in part the
hypertriglyceridemia observed in these patients.
PMID- 9640798
TI - Ovarian abscess with spontaneous vaginal drainage.
AB - The occurrence of a rare ovarian abscess, spontaneously drained through the
vagina after an abdominal hysterectomy is described. The treatment was an
oophorectomy. The various forms of primary ovarian abscess are discussed in
connection with these observations. This case illustrates the need for adequate
manipulation of the gonad during pelvic surgery in order to avoid parenchymal
contamination and the subsequent formation of such abscesses.
PMID- 9640799
TI - Medical controversies and systematic reviews: the heat and the light.
PMID- 9640800
TI - Microsurgical reconstruction during treatment of oncological diseases of head and
neck.
AB - In 37 oncological patients where extensive resections of the face, maxilla,
mandible or calva were necessary, microsurgical reconstructions were used in 27
cases as primary operations at the time of resection, and in 10 cases delayed or
secondary operations were made. 49 flaps were used. In five cases two flaps were
used in a single stage reconstruction, i.e. one flap for reconstruction of the
mandible or buccal and on the other for facial side of the face. During
operations a multidisciplinary approach of the surgical team comprising a
maxillofacial surgeon, ENT and plastic surgeon is preferred.
PMID- 9640801
TI - Treatment of a maxillary defect following resection of carcinoma.
AB - A group of 37 oncological patients with tumours of the head and neck where
extensive resection of the face, maxilla or mandible or calva was necessary,
comprised five patients with a typical defect after resection of part of the
maxilla including half of the palate and exenteration of the orbit. This
extensive defect causes discomfort to the patient and his environment--functional
i.e. impaired speech, and cosmetic. A satisfactory solution during reconstruction
of the maxilla without the need of skeletal reconstruction is microsurgical
transplantation of a narrow flap of the latissimus dorsi, usually with two
cutaneous islands--one to close the palate and the other to close the orbit and
face.
PMID- 9640802
TI - Functional and aesthetic consequences in the forearm after harvesting the Chinese
flap.
AB - We have evaluated the donor site after harvesting the chinese flap in 40 patients
operated at the Clinic of Plastic and Aesthetic Surgery of Brno between 1989 and
1994. We conclude that: 1--The hand function is not oustandly altered after
harvesting the flap, but in our study 11 patients (27.5%) indicated that they
have some limitation or impairment of their hand function. 2--Tolerance to
forearm deformity is considerable, but it depends on degree of the defect for
which the flap is transferred: 25 patients (62.5%) would like to elect a
different flap. 3--It is necessary to think about cosmetic consequences of the
chinese flap and consider other possibilities of the flap choice. Secondary
defect may be for the patient a problem even several years after operation.
PMID- 9640803
TI - Some thoughts and observations concerning the prevention of neuroma.
AB - Reliable prevention of neuroma is a problem the solution of which is still
outstanding. Compared to earlier methods, which mostly consisted in attempts to
stop axonal proliferation abruptly, it is now coming to be generally accepted
that the regenerative potential of the axons needs to be reduced gradually. The
methods most in accord with this view--centro-central anastomosis and capping of
nerve ends with a nerve or vein graft--are considered, adding personal
observations. A new variant that has shown special promise in animal experiments
involves using a nerve and a vein graft in combination. The method still requires
clinical verification.
PMID- 9640804
TI - Combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion
suppresses early postburn lipid peroxidation and improves deformability of
erythrocytes.
AB - The effect of FC-43 perfluorocarbon emulsion and alpha-tocopherol on lipid
peroxidative damage and deformability of erythrocytes was evaluated in rats (full
skin thickness burns over 15-20% of total body surface) at third hour after
burns. The animals were divided into five groups: (1) non-burnt non-treated
(controls); (2) burnt non-treated; (3) burnt but treated with alpha-tocopherol
("Serva", Germany, 20 mg/kg b.m. i.p.) (4) burnt treated with FC-43 emulsion
("Green Cross Corp.," Japan, 5 ml/kg, i.v.); (5) burnt treated with combination
of alpha-tocopherol (20 mg/kg) and FC-43 perfluorocarbon emulsion (5 ml/kg). In
the burnt non-treated group the concentration of alpha-tocopherol decreased by
38% (p < 0.05), the levels of malonyl dialdehyde (MDA) and fluorescent damaged
products raised by 32% (p < 0.001) and by 52% (p < 0.001) of the controls,
respectively, whereas the deformability of red blood cells diminished by 34% (p <
0.001). Both the accumulation of MDA and fluorescent lipid peroxidation products
and the decrease in deformability of affected cells were suppressed significantly
by alpha-tocopherol treatment which also prevented the decrease in erythrocyte
alpha-tocopherol content. FC-43 emulsion lowered the level of MDA but did not
restrain the reduction in erythrocyte deformability significantly. The combined
application of alpha-tocopherol and FC-43 emulsion immediately after thermal skin
injury decreases peroxidative membrane damage and improved erythrocyte
deformability more significantly than alpha-tocopherol at the third hour after
thermal skin injury.
PMID- 9640805
TI - The tissue adhesive indermil and its use in surgery.
AB - Indermil, in relation to the tissue adhesives described remains the state of the
art with regard to function and clinical outcome. The advantage of an inventory
sterile tissue adhesive that is to say one that is in the clinic or operating
theatre ready for immediate use on demand is the requirement of modern surgical
practice. Cost factors are also an important consideration in today's
environment. A research study by the Department of Health Economics at the
University of York found the cost of the Indermil tissue adhesive system
equivalent to absorbable sutures and produced projected savings per patient in
relation to conventional sutures with respect to theatre time and return
patients' visits (6). In parallel a survey of patients showed 90% would prefer
wound closure by an adhesive in relation to traditional sutures. There are few
areas of surgical practice which cannot find some application for tissue
adhesives. The growing international interest in adhesives and their application
would confirm their importance and potential in surgery.
PMID- 9640806
TI - Challenges of family planning in Africa.
PMID- 9640807
TI - Family planning knowledge, attitude and practice amongst males in a Nigerian
urban population.
AB - A study to investigate men's knowledge, attitude and practice of family planning
was carried out in Enugu, South-eastern Nigeria between September and December
1996. A total of 380 adult working males were studied. A high proportion of the
respondents had knowledge of and possessed positive attitude to family planning,
even though a lesser proportion actually used family planning methods. Ninety per
cent of the respondents accepted the decision that the number of children in the
family should be made by the couple. While over 32 per cent of the men believed
that the wife alone should use family planning methods, only 10 per cent thought
it was the husband's role to use family planning methods. There is need for the
present integrated national MCH/family planning programmes to be adapted for use
by men.
PMID- 9640808
TI - Awareness and use of family planning methods among married women in Ibadan,
Nigeria.
AB - A study of awareness and use of family planning methods among 1188 married women
aged 15-40 years, attending antenatal clinic in four different locations,
conducted in Ibadan, Nigeria between May to December 1995 is reported. Most
respondents (94.3%) were aware of the use of family planning but only 12.0% had
ever visited a family planning clinic. Awareness of specific methods was 82.6%
for condoms, 75.7% for oral contraceptives, 75.5% for injectable contraceptives
and 65.3% for intrauterine device. Current use of family planning methods was low
with 10.0% using withdrawal, 8.1% oral contraceptives, 5.2% using intrauterine
devices and 4.7% using condoms. Perceived constraints to the use of family
planning methods included husband's opposition, fear of complications and
perceived insufficient knowledge about family planning methods. It is concluded
that there is a knowledge-practice gap in the use of family planning methods
among married women in Ibadan, Nigeria. Improved education strategies and better
access to services are needed to solve these problems.
PMID- 9640809
TI - Pain control in voluntary surgical contraception.
AB - The reduction of anxiety and control of pain in 1,546 clients undergoing
voluntary surgical contraception (VSC) is presented. Psychological support
through adequate counselling and abdominal breathing exercises are vital. General
anaesthesia was used in 254 (16.4%) of the clients; sedation plus local
anaesthetic agents in 296 (19.2%) while local anaesthetic alone was used in 996
(64.4%) of clients. There was progressive shift from the use of general
anaesthesia (GA) to local anaesthesia (LA), particularly for the minilaparotomy
procedure following the introduction of Association for Voluntary Surgical
Contraception (AVSC) programme in our department since this type of anaesthesia
was cheap, safe, affordable and readily available. Recommendations for successful
VSC techniques include gentle tissue handling, proper use of the correct
instruments to reduce painful stimuli, while low dose intravenous sedation should
be used only when necessary. Minilaparotomy under local anaesthesia (ML/LA) has
been successfully established in Jos University Teaching Hospital, Jos, Nigeria.
PMID- 9640810
TI - Evaluation of weaning diets in peri urban Kumasi, Ghana.
AB - This work evaluates the commonly used weaning diets in peri-urban Kumasi, Ghana,
in terms of the type of diets, daily energy and nutrient intakes of the infants,
frequency of feeding, and the chemical composition of the diets. Women with
children of up to two years old in peri-urban communities of Kumasi municipality
of Ghana, were interviewed in a cross-sectional survey. One hundred and seventy
two mothers were randomly sampled and questioned on their socio-economic
characteristics, types of weaning diets they give to their children, and the
dietary intakes of their children. Composition of the commonly used weaning
diets, and the daily energy and protein intakes of the children were determined.
Liquid weaning diets were introduced at a mean age of 2.2 +/- 2.4 months earlier
than recommended, but solids were at appropriate time (5-7 months). The energy
and protein intakes of the children were low, meeting only 49% and 90% of their
respective recommended daily intakes. This is attributed to the low energy and
protein densities of the commonly used liquid diet, koko, and low energy and
nutrient contents of other weaning diets. It is recommended that an innovative
nutrition education package that re-emphasises the need to introduce weaning
diets with continued frequent breast feeding to ensure adequate caloric and
protein intakes should be designed and implemented.
PMID- 9640811
TI - Upper gastrointestinal mucosal lesions in dyspeptic patients with homozygous
sickle cell disease in Kenya.
AB - A case controlled study comprising 51 patients with homozygous sickle cell (HbSS)
disease who complained of dyspepsia and 41 age and sex matched non-HbSS control
dyspeptic patients was carried out, to look at upper gastrointestinal mucosal
lesions associated with dyspepsia. Upper gastrointestinal tract (UGIT) endoscopy
was performed with gastric control biopsy taken for histology. Thirty two (62.3%)
of the HbSS or sickle cell anaemia (SCA) patients had upper gastrointestinal
pathology at endoscopy as compared to 17 (41.5%) of controls. The difference was
significant at p = 0.042. Bile reflux (47%) was the predominant abnormal
morphological finding in SCA patients while duodenal ulcer was the most common
morphological finding in dyspeptic controls. The prevalence of duodenal ulcer in
controls (22%) though higher than in SCA patients (9.8%), was not statistically
significant p = 0.18. Gastric ulcer was not found in SCA patients. Duodenal ulcer
was commoner in males than females in both cases and controls with a ratio of 4:1
and 3.5:1 respectively. Only four (7.8%) SCA patients and one (2.4%) of controls
had normal mucosa at histology, the rest had evidence of histological gastritis.
We could not draw any correlation between non-steroidal anti-inflammatory drugs
(NSAIDS) use and UGIT findings. Since the proportion of SCA cases with UGIT
abnormalities was significantly high, we recommend that dyspeptic SCA patients
undergo UGIT investigations including endoscopy to maximise their clinical care.
PMID- 9640812
TI - Calcitonin gene-related peptide immunoreactive (CGRP-IR) intradental nerves in
the dog.
AB - Calcitonin gene-related peptide (CGRP) is the most frequently occurring peptide
in sensory neurons in the rat. Most of the Calcitonin Gene-Related Peptide
Immunoreactive (CGRP-IP) nerves have been found to be Capsaicin-sensitive
suggesting an involvement in certain types of pain. In the dental pulp CGRP-IR
nerve fibres have been studied in the rat, guinea pig, cat, sheep, pig, cow and
horse but not in the dog. Extensive sprouting of CGRP-IP intradental nerves has
been demonstrated in the teeth with pulpal inflammation in rat molars. In the
present investigation the occurrence and distribution of CGRP-IR intradental
nerves both in the normal and the injured and inflamed teeth of the dog was
studied. Immunolabelling was done by the Avidin-Biotin Complex (ABC)
immunoperoxidase technique. CGRP-IR intradental nerves were demonstrated in the
dog. The pattern of distribution was found to be similar to that in other animal
species. However, the tip one third of the coronal pulp was sparsely innervated
compared to that in the rat. Also much fewer fibres were seen to penetrate
predentine and dentine, and this appears characteristic of the dog teeth.
Sprouting phenomenon seen in the rat was not found in the dog teeth. It is
suggested that there might be a species difference in the innervation pattern of
CGRP-IR intradental nerves between the rat molar and the dog canine and incisor
teeth.
PMID- 9640813
TI - Relationship between parasite load and immune responses in early stages of
Leishmania donovani infection in inbred BALB/c mice.
AB - The aim of this study was to determine if a correlation exists between Leishmania
donovani parasite load and the corresponding humoral and cellular mediated immune
responses in the early stages of Leishmania donovani infection in inbred BALB/c
mice. Five groups of ten BALB/c mice each were inoculated intraperitoneally with
stationary phase metacyclic promastigotes of Leishmania donovani at doses 1 x
10(2), 1 x 10(4), 10(6) and 1 x 10(8) respectively per mouse. Group five mice
were not manipulated in any way and were left to serve as control. At weekly
intervals, for five weeks, the mice were assayed for cellular mediated immune
responses to leishmania antigen by the delayed type hypersensitivity skin test
(DTH) and humoral responses by the direct agglutination test (DAT) and the enzyme
linked immunosorbent assay (ELISA). A correlation was established between
parasite load and humoral responses as assayed by DAT and ELISA techniques. This
study demonstrates that it is possible to diagnose visceral leishmaniasis in
experimentally infected laboratory mice by DAT and ELISA. These techniques have
the potential in screening large numbers of animals suspected to be reservoirs of
visceral leishmaniasis by examining the peripheral blood taken from the tail of
the animal.
PMID- 9640814
TI - Antibiotic sensitivity of endemic Shigella in Mbarara, Uganda.
AB - We analysed the chimio-sensitivity to antibiotics of endemic strains of Shigella
isolated in Mbarara district, southwest Uganda. Twenty four strains were
isolated, of which none was sensitive to cotrimoxazole and eight (33.4%, 95% CI
[15.6-55.3]) to ampicillin, the two antibiotics recommended to treat dysentery
during non epidemic periods in Uganda. Two isolates were resistant to nalidixic
acid and none was resistant to the fluoroquinolones (Ciprofloxacin, Norfloxacin).
It is concluded that the results of this survey could be used to facilitate the
elaboration of a new treatment protocol to treat endemic dysentery cases in
Uganda.
PMID- 9640815
TI - In-vitro activity of piperacillin and tazobactam combination against clinically
significant bacteria.
AB - The in-vitro activity of piperacillin/tazobactum which is not among the routinely
tested antibiotic at the Public Health Bacteriology Laboratory, Parirenyatwa
Hospital, Harare, Zimbabwe was evaluated for its activity against bacterial
pathogens using the Kirby-Bauer disk diffusion method. Piperacillin/tazobactum
showed superior in-vitro activity against both gram positive and gram negative
bacteria when compared with routinely tested antibiotics such as gentamicin,
erythromycin, tetracycline, penicillin, chloramphenicol, fusidic acid and
clindamycin and the difference was statistically significant (p < 0.05).
Ciprofloxacin showed in-vitro activity comparable to that of
tazobactam/piperacillin. Specifically, 96% of gram positive isolates (comprising
Streptococcus pyogenes, Staphylococcus aureus, coagulase negative staphylococci
and Streptococcus pneumoniae were sensitive to piperacillin/tazobactam. For gram
negative organisms, 98% of Haemophilus influenzae Shigella spp, Klebsiella spp
were also sensitive to the combination. The broad spectrum of activity of
piperacillin/tazobactam shows that the potential of the drug combination for the
treatment of infections caused by diverse microorganisms should not be
underestimated. We recommend its inclusion in routine antibiotic sensitivity
testing in our hospital.
PMID- 9640816
TI - Health effects of cassava consumption in south Ethiopia.
AB - Health problems associated with cassava consumption was studied in three villages
(Kodowono, Lotte and Woidewashe) of Gamo-Gofa, South Ethiopia. Total goitre rate
(% TGR) increased with increasing rate of cassava consumption while, urinary
iodine excretion (UIE) was found to be in the normal value range for the three
villages. In both males and females incidence of goitre after the introduction of
cassava to Kodowono village was significantly higher than before introduction of
cassava (p < 0.001). This may indicate that the high rate of goitre is attributed
to the frequency of cassava consumption. Of 450 individuals interviewed for
health problems associated with cassava meal consumption, 50% reported that they
were suffering from epigastric burning pain and dizziness while 38.7% reported
abdominal distention and vomiting. Vomiting was relatively higher in the age
group 20 years and below than it was in those above 20 years of age. These
problems may be attributed to cassava consumption because, cassava contains
cyanide which results in intoxication when poorly processed cassava meal is
taken. Goitre prevalence and health problems attributed to cassava consumption
therefore, necessitate an intervention programme to control iodine deficiency
disorders (IDD), develop appropriate processing techniques to eliminate cassava
toxicity and educate villagers on how to prepare safer meals from cassava.
PMID- 9640817
TI - Smoking--an emerging risk factor for renal diseases.
AB - The health, economic and social costs of smoking are enormous and well known to
physicians. Smoking results in a lot of morbidity and mortality mainly related to
cardiovascular disease, cancer and pulmonary disease. The effect of smoking on
the kidneys is little appreciated. It is the purpose of this review article to
give evidence from available literature that smoking is indeed deleterious to the
kidneys and may result in progression of chronic renal failure to end stage renal
disease. It is concluded that nephrologists, and indeed all physicians, should
make a concerted effort to save their patients from this vice.
PMID- 9640818
TI - Human antibody response to Moraxella catarrhalis antigens.
AB - Moraxella catarrhalis was isolated from 68 of 200 (34%) sputum and 56 (28%)
nasopharyngeal swab samples of patients with community-acquired pneumonia. Of the
68 pneumonia patients, 42 (61.8%) were males and 26 (38.2%) females. Fifty one of
the 68 patients (75%) had chronic underlying diseases. beta-lactamase was
produced by 37 (54.4%) of the 68 sputum samples and 32(57.1%) of the 56
nasopharyngeal isolates. In an ELISA using outer membrane protein antigens of M.
catarrhalis against patient sera showed 40 of 68 (58.8%), and 43 of 68 (63.2%)
significant increase in convalescent to acute sera when IgA, IgM and IgG3 were
used respectively. In control sera only of 30(3.3%) and none showed significant
antibody rise when IgA, IgM and IgG3 conjugates were used respectively (P <
0.05).
PMID- 9640819
TI - Surgery in a rural hospital: experience from northern Nigeria.
AB - Over a 5-year period in a rural hospital in Northern Nigeria, 949 patients were
operated on, constituting 84.7% of all surgical admissions. Nearly one half were
emergency procedures. The majority of the patients were young (mean age 36.0
years) and predominantly male (M:F = 1.5:1). A wide variety of surgical
procedures were performed but overall 85% were not of a complex nature. Mortality
was 4.8%, due mostly to septic complications. It is suggested that most of the
surgical procedures in rural Africa can be performed by general duty doctors with
surgical experience and they should be taught and encouraged to perform these
operations. The importance of relevant research to solve local problems is
highlighted and the planning of primary health care to include more primary
surgery emphasised.
PMID- 9640820
TI - Cholelithiasis in young Saudi women.
AB - We studied some of the factors associated with gallstones in a sub population of
Saudi women who presented with cholelithiasis at a rather young age, 17-30 years.
We determined the weight, height, ideal weight, overweight, Quetelet index, ideal
Quetelet index, and parity in 152 such women designated the study group and in
another aged matched group of 152 women without biliary disease designated the
control group. Although the mean weights of both groups were greater than ideal,
the mean weight, level of overweight, and mean Quetelet index in the study group
were greater than those of the controls at virtually all age groups (p > 0.001).
In the study group, comparison of the 17-25 year olds with the 26-30 year olds
showed close similarity in weight, Q index, and level of overweight (p = 0.50).
There was no significant difference in parity between the study group and the
controls. We conclude that obesity is a significant factor in the development of
cholelithiasis in Saudi women who develop symptomatic gallstones in the age group
17-30 years.
PMID- 9640821
TI - Recurrent varicose veins.
AB - Recurrence of varicose veins after treatment has been reported as being between
7% and 65%. During the five month period from August to December 1993, 400
operations on 265 patients were performed for varicose vein disease. Of these, 53
patients had presented with recurrent vein disease in 72 limbs (18%). All
patients underwent Duplex scanning of their deep and superficial systems and
sites of venous incompetence were identified. The sapheno-femoral junction (SFJ)
was found to be incompetent in 52 limbs, of which 31 had previously undergone
flush ligation. Sapheno-popliteal junction (SPJ) was incompetent in 33 limbs,
while the long saphenous vein (LSV) was found to be incompetent in 67 cases.
There were no major complications in this group. Minor complications occurred in
10 cases (14%), mainly in the form of thigh paraesthesia. The more common causes
of recurrent disease have been identified and therefore, it should be possible to
reduce its incidence. Duplex scanning is essential for any unit dealing with
recurrence.
PMID- 9640822
TI - Relapse of Hodgkin's disease after 10 years of complete remission: case report.
AB - A 17 year old male patient with nodular sclerosis Hodgkin's disease had a relapse
of lymphocyte depleted type ten years after entering complete remission with
chemotherapy and radiotherapy. This is the first documented case in our
experience of relapse after very long disease free interval. A review of the
literature of late relapses in Hodgkin's disease is also presented. Relapses have
been recorded from three years to twenty years, although few very late forms are
registered. Long term follow up will be necessary to document the role of the
different therapeutic regimen.
PMID- 9640823
TI - Recent infectious disease outbreaks in Kenya: have we been caught unaware?
PMID- 9640824
TI - Pattern of resolution of tachypnoea and fever in childhood pneumonia.
AB - Acute lower respiratory infections (ALRI) account for one fifth of deaths among
children below five years of age and pneumonia is responsible for about 70% of
all ALRI deaths. Interventions with antibiotics have shown reduction in pneumonia
case-fatality rates. However, there is room for further reduction of deaths from
pneumonia through improved monitoring and follow up system. We studied the
pattern of resolution of tachypnoea and fever among 108 children who presented to
our outpatient clinic with non-severe pneumonia and among 102 children who were
admitted for severe pneumonia. We found that tachypnoea was present in 18% and
23% after 72 hours of initiation of antibiotics and fever resolved completely
after 48 hours and 72 hours of initiation of therapy in non-severe cases of
pneumonia among children two to 11 months and 12 to 59 months of age
respectively. Conversely, among cases of severe pneumonia on day 5 of initiation
of treatment, tachypnoea and fever were present in 65% and 51% respectively in
children two to 11 months old and in 53% and 60% respectively in children 12 to
59 months old. Respiratory rate increased with increase in body temperature at an
average rate of four breaths per minute for every 1 degree C rise. Our study
suggests that body temperature and respiratory rate can be used to monitor the
clinical course of non-severe pneumonia. Further research is needed to identify
other clinical signs that will help the health worker to decide improvement in
attacks of severe pneumonia.
PMID- 9640825
TI - Selected laboratory tests in febrile patients in Kampala, Uganda.
AB - A study was undertaken to determine the role of typhoid in febrile illness. It
was found that in 1992, Salmonella typhi, the causative agent of typhoid, played
a 2.3% role in 25404 diagnostic specimens sent to Mulago Hospital, Kampala, the
largest hospital in Uganda. The rates of isolation fell gradually from 2.3% in
1992 to 0.3% by 1995. Instead malaria was found to play a major role in febrile
illnesses. Out of 355 patients attending a private clinic in Kampala, whose blood
was examined for both malaria and typhoid, 97% were positive for malaria
parasites compared to 0.84% with significant O and H Salmonella typhi antibody
titres of > 1:80. Also malaria parasites were found in 60% (out of 105) of
patients who had had persistent fevers and in whom doctors had also requested for
HIV antibodies. Those who had HIV antibodies alone were six per cent and the ones
with both were 28%, a finding which showed relatively low association of malaria
and HIV. Where multiple tests were requested on one patient having general
malaise or body joint pains and/or constant headaches, malaria was found to play
a major role (73%) compared to syphilis (4.3%) and brucellosis (13.3%). Malaria
parasites were seen in normal sizes and in somehow young or stunted forms. The
latter were found more often in patients who had experienced one or a combination
of the following: intermittent fevers, backache, headache, tiredness, joint
and/or neck pains, and who had already received treatment for malaria.
PMID- 9640826
TI - Bacterial meningitis in children admitted in hospitals within Nairobi.
AB - Four hundred and ninety nine children (aged between one month and five years)
admitted with clinical features of meningitis were recruited in cross-sectional
survey of bacterial meningitis in hospitals within Nairobi. Lumbar punctures were
done on all of them and the cerebrospinal fluid (CSF) analysed bacteriologically
and serologically for the common causative organisms. Two hundred and fifty
(50.1%) cases were diagnosed clinically as having meningitis. Of these, 132
(52.8%) had turbid CSF specimens, while 118 (47.2%) were clear. When turbid CSF
specimens were cultured, 83 (62.8%) yielded three common bacterial micro
organisms namely; Neisseria meningitidis, Streptococcus pneumoniae and
Haemophilus influenzae in that order of frequency. The implications of these
findings in paediatric meningitis together with the drug sensitivity patterns is
presented and discussed.
PMID- 9640827
TI - Cytoprotective effects of alpha tocopherol against liver injury induced by
extrahepatic biliary obstruction.
AB - There are several important aetiologies of extrahepatic biliary obstruction
(EBO). If EBO is surgically reconstructed in the critical time period, liver
damage can be halted or reversed. In this golden period, lipid peroxidations
significantly intensify liver defects. We hypothesised that alpha tocopherol
(alpha-T) could protect the liver from the damage caused by response to EBO. In
standard conditions, albino rats of Wistar strain were divided into two groups.
All rats underwent double ligations and divisions of common bile ducts (CBD). One
of these groups received alpha-T (CBDL-alpha-T). The other CBDL animals received
intramuscular injections of normal saline (CBDL-NS). Serum samples were taken for
biochemical analyses by light microscopy. The data showed a decrease in plasma
bilirubin and liver enzyme levels in CBDL-alpha-T group, when compared with CBDL
NS (p < 0.05). Morphologic analyses showed better results for CBD-alpha-T. Serum
levels of Malonyldialdehyd (MDA) in the CBDL-alpha-T group was 9.2 +/- 3.4 nmol/g
compared to that in CBDL-NS, 12.3 +/- 4.4 nmol/g (p < 0.05). In conclusion, a
dramatic protective effect of alpha-T on functional and structural features of
the liver in rats with EBO was demonstrated. The data suggest that EBO may cause
liver damage by stimulation of lipid peroxidation and that alpha-T may slow down
liver damage in this setting.
PMID- 9640828
TI - Appendicitis among African patients at King Edward VIII Hospital, Durban, South
Africa: a review.
AB - This retrospective study of 645 black patients, carried out over a five year
period, showed that appendicitis is twice as common in males as in females and
that it occurs predominantly in young people (median age 20 years). The classical
presentation of periumbilical pain (16%) was outnumbered by right iliac fossa
pain (36%) and non-specific pain (27%). The majority perforated (43%) and
appendiceal inflammation was second commonest (37%). The negative appendicectomy
rate was 8.8% and there was a diagnostic error of 14%. Mortality was two per cent
mainly from patients complicated by peritonitis. Hospital stay was 7 +/- 7 days,
with the longest stay following peritonitis. A diagnosis of appendicitis should
always be entertained in an African patient presenting with an acute abdomen and,
where the diagnosis is in doubt, a laparotomy should be performed.
PMID- 9640829
TI - Endoscopic findings and prevalence of Helicobacter pylori in Kenyan patients with
dyspepsia.
AB - One hundred and twenty consecutive patients above 12 years of age with dyspepsia
were studied from June 1993 to September 1994. They underwent upper
gastrointestinal endoscopy to find the mucosal lesions which were associated with
their dyspeptic symptoms. At endoscopy gastric mucosal biopsies were taken in
order to identify Helicobacter pylori (H. pylori) using three different
techniques: culture, histology and the rapid urease test. Normal looking mucosa
was the commonest single endoscopic finding, accounting for 34.2%, followed by
gastritis 31.7% and duodenal ulcer 29.2%. However, when duodenal ulcers and
gastric ulcers were put together, then peptic ulcer was the most prevalent
finding accounting for 38.4%. Peptic ulcer was the most prevalent pathological
finding in both young (less than 50 years) and older patients (50 years and
above). Duodenal ulcer was more prevalent than gastric ulcer in the younger age
group with a ratio of 5.8:1, however, the ratio in the older age group was 1:1.
Gastric cancer was only found in patients aged 50 years and above, accounting for
17.4% of dyspeptic symptoms in this age group. Females were found to have more
normal endoscopic findings than males (59.6%, versus 17.8% respectively). The
difference being statistically significant (p < 0.001). All our cases of peptic
ulcer disease had evidence of H. pylori infection while dyspeptic patients with
normal endoscopic mucosal findings had H. pylori in 80.5% of cases. The
difference in prevalence of H. pylori in the two groups was statistically
significant (p < 0.001). Surprisingly, evidence of H. pylori in gastric cancer
cases was very low in this study, being found in only 25% of patients.
PMID- 9640830
TI - Pattern of peptic ulcer disease in Zaria, Nigeria.
AB - The pattern of peptic ulcer disease in Zaria has been that of an increasing
frequency of perforation, reaching a peak of 45% by 1983. In a retrospective
study of 88 consecutive patients managed surgically for duodenal and gastric
ulcers between 1984 and 1995, 41% had gastric outlet obstruction and only 17% had
perforation. However, the ratio of perforated duodenal ulcer: perforated gastric
ulcer has more than doubled from 2.6:1 to 6.5:1. Until now the pattern of peptic
ulcer disease in northern Nigeria was different from that in southern Nigeria and
most parts of black Africa but this review suggests a reversion to the pattern in
these other places. Though these findings may be due to the effects of a changing
economy, they may represent a change in the intrinsic behaviour of peptic ulcers
in our environment. Ulcer perforation continues to carry a high mortality and
truncal vagotomy and drainage remains the surgical treatment of choice for
duodenal and gastric ulcers in our institution.
PMID- 9640831
TI - Caretakers' perceptions of clinical manifestations of childhood malaria in holo
endemic rural communities in Tanzania.
AB - A cross-sectional household survey was carried out in Kibaha district, Tanzania
to obtain caretakers' knowledge on symptoms of childhood malaria in children
under five years of age in relation to its management. A total of 1530 caretakers
were interviewed, 620 (40.5%) reporting malaria attacks among their children in
the last three months of which, 432 (70%) reported that the attacks were severe.
Only 15.7% (68/432) of those reporting severe attacks could mention convulsions
as symptoms of severe malaria, while fever and vomiting were mentioned as
symptoms of severe malaria by 93.3% (403/432) and 52.3% (226/432) of the care
takers respectively. Higher level of education was significantly associated with
knowledge of symptoms of severe malaria, also with promptness in taking
management action. The fact that most of the caretakers reported fever and
vomiting as symptoms of severe malaria, and hence the observed high proportion of
reported severe malaria, implies that the communities under study do not perceive
febrile convulsion as being a symptom of severe malaria. The implication of these
findings on the control of malaria through treatment on demand are discussed.
PMID- 9640832
TI - Wild polio virus surveillance in the sewage system of selected communities at the
risk of poliomyelitis in southwest Nigeria.
AB - Twenty two sewage samples collected from eleven locations among communities at
risk of poliomyelitis in the southwestern part of Nigeria were screened for the
presence of polio virus. The virus was isolated from seven of the samples. All
the isolates were type 1 wild polio virus, an indication that all the isolates
were from human contamination and that the wild polio virus is still very much in
circulation in Nigeria many years after the Expanded Programme on Immunisation
was introduced. It can be concluded from this study that polio immunisation
campaign has not been successful in Nigeria considering the number of wild polio
virus isolated from the sewage samples since virological examination of sewage
has been used to document the effect of vaccination campaigns.
PMID- 9640833
TI - Cryptosporidium and other parasites in Ethiopian AIDS patients with chronic
diarrhoea.
AB - Previous studies in other African countries have shown high prevalences of
Isospora belli and Cryptosporidium parvum infections in acquired immunodeficiency
syndrome (AIDS) patients with chronic diarrhoea. However, there is lack of
information regarding these infectious agents in Ethiopian AIDS patients. Thus,
this investigation has been aimed at determining the prevalence of
Cryptosporidium and other related gastrointestinal parasites in AIDS patients
with diarrhoea in seven Addis Ababa hospitals. Stool specimens from 246
clinically diagnosed AIDS patients were parasitologically screened for parasitic
infections constituting HIV-negative with diarrhoea and HIV-positive without
diarrhoea control groups. A variety of intestinal protozoa and helminths were
found in 50% of AIDS patients and 42% of the controls. Cryptosporidiosis was
detected in 38(25.9%), Isosporiasis in two (1.4%), and Blastocystosis in one
(0.7%) of the AIDS patients with diarrhoea. The occurrence of cryptosporidiosis
among the AIDS patients and possible explanation of the increasingly high study
subjects with diarrhoea but without identifiable parasites is discussed.
PMID- 9640834
TI - Obstetric outcome in the unbooked mother.
AB - This study aimed at determining the outcome of pregnancy in unbooked mothers with
regard to maternal complications and foetal outcome. This retrospective study was
based on investigations of medical records of 467 unbooked mothers who presented
for delivery at the Obstetrics Unit at King Khalid University Hospital, Riyadh,
during the period 1991 and 1992, and 415 booked mothers with regular clinic
attendance selected as controls. Data collected from the records included
patients' socio-demographic characteristics, past obstetric history, prevalence
of pregnancy-related diseases, and data relating to labour, delivery, and foetal
outcome. Chi-square test and Fisher's exact test were used for assessing the
statistical significance of the association between the various factors which
were investigated. The tendency for mothers to be booked was found to be
significantly associated with their age, occupation, parity, and gestational age
at delivery. Booked and unbooked mothers did not differ significantly in relation
to the mode of delivery and foetal outcome, although the prevalence of previous
complications of pregnancy was generally lower among unbooked mothers. There was
no statistically significant association between the absence of antenatal care
and outcome of pregnancies, unbooked mothers had a higher proportion of MICU
admissions and dead babies compared with the controls. Educating the community
about the benefits of receiving regular antenatal care, even if at primary care
level, may be of great importance in improving the pregnancy outcome.
PMID- 9640836
TI - Injury pattern during team handball competition in east Africa.
AB - Team handball is a fast, explosive sport, and injury risk is inevitable. There is
need to define the risk factors in order to formulate preventive, treatment and
rehabilitation measures. This study investigated the nature, aetiology, mechanism
and anatomical localisation of injuries observed among male and female players
during the tenth edition of the East and Central Africa Senior Clubs
Championships (9th-17th April, 1995) in Nairobi, Kenya. There were nine male and
five female teams from Kenya, Uganda, Tanzania and Ethiopia which played nineteen
and ten matches respectively leading to 52(77.61%) and 15(22.39%) injuries. The
matches were observed and the injuries recorded live by trained researchers and
the result confirmed after the match. The commonest injuries were contusions
(64.18%). Most injuries were caused by another person (85.07%), majority of them
occurring due to collision (55.22%). The head suffered most injuries (59.24%) and
many players got more injured while attacking than defending. In all, 56.7% of
the injuries were observed in the second half. Generally, only 38.81% of the
injuries led to a substitution of player. This pattern of injuries was the same
for both male and female players. More studies of this nature are recommended in
order to clearly define injury risk in team handball and, thus, preventive,
treatment and rehabilitation measures.
PMID- 9640835
TI - Rehabilitation of heroin and cocaine abusers managed in a Nigerian psychiatric
hospital.
AB - Eighty patients, managed primarily for heroin and cocaine dependence at the Drug
Rehabilitation Unit of Psychiatric Hospital, Yaba, Lagos, were followed up
monthly for a period of 12 months post-discharge and assessed with regard to
continued substance use, employment status and illegal activities. The management
package included full assessment, detoxification, treatment of associated
physical conditions, group therapy sessions, occupational and vocational
rehabilitation. The sample was predominantly male (91%), young adults (mean age
29.1 years; SD 5.99) and single (58%). Although 95% had some formal education,
many were school drop-outs, and only 31.3% were gainfully employed. The majority
(84%), used a combination of heroin and cocaine, almost all on a daily basis,
mainly by smoking and "chasing the dragon" (95%). Other substances reportedly
used preadmission were alcohol (22.5%), cannabis (76.3%) and tobacco (97.5%).
Less than one half (43.8%) completed the minimum one month required for inpatient
treatment. Only seven (8.7%) attended the follow-up clinic regularly, but all
defaulters were assessed in their homes. The level of heroin, cocaine and
cannabis use, as well as report of illegal activities, dropped sharply from the
first month post-discharge, but started to rise again (albeit slowly) by the
second half of the follow-up period. There was only a slight insignificant gain
in employment status of patients during the follow-up period. The community-based
management approach is strongly advocated as a way of addressing the several
factors identified in this study as militating against the successful management
of substance abusers.
PMID- 9640837
TI - Chloroquine and cardiac arrhythmia: case report.
AB - A case of a sixty two year old white man with Plasmodium vivax malaria, who has
shown chloroquine associated acute cardiac arrhythmia is reported.
PMID- 9640838
TI - Opsoclonus-myoclonus associated with traditional medicine ingestion: case report.
AB - A case of Opsoclonus-Myoclonus occurring in a young man, in association with
traditional herbal medicine consumption is presented. Clinical and laboratory
investigations did not reveal any of the known aetiological associations of the
Opsoclonus-Myoclonus syndrome, raising the possibility that the traditional
herbal medicine may be aetiologically implicated. This report highlights the need
for proper identification and documentation of the contents of common herbal
remedies and their possible side effects amongst Africans.
PMID- 9640839
TI - Cervicofacial actinomycosis after partial mandibular resection: case report.
AB - An unusual case of cervicofacial actinomycosis in a 60-year old male Nigerian is
reported. The patient had had partial mandibular resection for plexiform
ameloblastoma one year earlier with insertion of Kirschner wire to serve as a
splint. The authors highlight the possible pathophysiology of this condition. It
is suggested that clinicians be aware of the various modes of presentation and
natural history of the disease to facilitate prompt diagnosis and appropriate
treatment. This will assist in forestalling the numerous complications that may
result from actinomycosis.
PMID- 9640840
TI - Gastro-intestinal tuberculosis: an emerging diagnostic dilemma.
AB - Nine cases of gastrointestinal tract tuberculosis seen by the author in 1995/96
are reported. In all the patients, the final diagnosis could only be established
histologically. Pre-operative clinical examination and investigations had
suggested otherwise. Six of these patients were HIV positive. This communication
suggests that immunocompromised individuals are at increased risk of
gastrointestinal tuberculosis. Clinicians, therefore, should bear in mind
possible co-existence of gastrointestinal tract (GIT) tuberculosis and HIV when
dealing with patients suffering from gastrointestinal tract diseases of unknown
origin.
PMID- 9640841
TI - Unusual neuropsychiatric manifestations of hypoparathyroidism: report of two
cases.
AB - Clinical, laboratory and radiological features of two cases of hypoparathyroidism
presenting with pure neurological disease are described. The first patient has
choreoathetosis and the second has mutism, locked jaw bilateral papilloedema and
generalised tonic clonic epilepsy. Computerised tomography of the brain showed
extensive calcification in the gray and white matter in both cases. Such
combination of neurological manifestation of the disease and extensive cerebral
calcification is rarely encountered and reported. It is concluded that brain
calcification, which is generally believed to be asymptomatic, can cause frank
neurological disease when it is extensive.
PMID- 9640842
TI - Cancer cell cycle and adoptive immunotherapy using lymphokine-activated killer
cells.
AB - The mechanism underlying the lymphokine-activated killer (LAK) cell cytotoxicity
to tumor cells in LAK therapy was studied using flow cytometric cell cycle
analysis of Daudi cells. It was suggested that the degree of LAK cell
cytotoxicity varied depending upon the phase of the cell cycle that the Daudi
cells were in: the resting (G0)-phase/preparation for DNA synthesis (G1)-phase,
the DNA synthesis (S)-phase or the preparation for mitosis (G2)-phase/mitosis (M)
phase. The levels of expression of intercellular adhesion molecule-1 (ICAM-1),
lymphocyte function-associated antigen-3 (LFA-3) and fibronectin (FN), surface
antigens playing important roles in LAK cell cytotoxicity, in the different
phases of the Daudi cell cycle have been investigated. The level of the
expression of ICAM-1 and LFA-3 was significantly higher in S-phase cells and G2/M
phase cells relative to that in G0/G1 phase cells. The level of expression of FN,
however, was significantly lower in S-phase cells and G2/M-phase cells in
relation to that in G0/G1 phase cells. On the basis of these results, it may be
inferred that the degree of LAK cell cytotoxicity is closely related to the cell
cycle phase that the Daudi cells are in and the level of expression of surface
antigens associated with the cell cycle phase. For Daudi cells treated with cis
diamminedichloroplatinum (II) (CDDP) and mitomycin-c (MMC), the enhancement of
the degree of LAK cell cytotoxicity was directly related to the decrease in the
proportion of cells in the S-phase. It may be suggested, therefore, that the
proportion of cells in the S-phase in a tumor serves as an index of the
sensitivity of the tumor cells to LAK cell cytotoxicity, and that designing a
therapeutic strategy on the basis of the analysis of tumor cell cycle would help
to improve the success of LAK therapy.
PMID- 9640843
TI - Enhancement of eosinophil survival by lipopolysaccharide through releasing
granulocyte-macrophage colony stimulating factor from mononuclear cells from
patients with bronchial asthma.
AB - BACKGROUND: The mechanism of bronchoobstruction in asthmatics following
inhalation of lipopolysaccharide (LPS) is unclear. OBJECTIVE: In this study we
have investigated the effects of the LPS on eosinophil survival rate in
stimulating peripheral blood mononuclear cells (PBMCs) from patients with asthma.
METHODS: PBMC supernatants from 10 asthmatic patients and 4 healthy subjects were
compared for eosinophil survival rate using the same purified eosinophils. Two x
10(6) cells/ml of PBMCs were cultured for 24 hours in RPMI 1640 containing 10%
fetal bovine serum along with 10 micrograms/ml of LPS. 10(6) cells/ml of
eosinophils were incubated for 96 hours in the presence of PBMC-derived culture
supernatants at 75% in volume. RESULTS: The viability of eosinophils incubated
with PBMC supernatants from asthmatic patients stimulated with LPS was higher,
62.5% +/- 10.6% (mean +/- SD), than that without LPS, 26.9% +/- 10.8%, and also
higher than that of PBMCs from healthy subjects with LPS, 40.0% +/- 15.4%. This
increasing activity of asthmatic PBMC stimulated with LPS was markedly inhibited
from 72.2% +/- 9.7% to 38.5% +/- 6.8% by addition of mouse anti-human GM-CSF
antibody to the PBMC supernatant but not mouse anti-human IL-5 antibody.
CONCLUSION: These results suggest that LPS enhances eosinophil survival in
asthmatics by increasing the production of GM-CSF from PBMCs.
PMID- 9640844
TI - Intranuclear expression of cyclin D1 protein as a useful prognostic marker for
mantle cell lymphoma.
AB - Mantle cell lymphoma (MCL) has a characteristic chromosomal translocation,
t(11:14) (q13;q32) involving rearrangement of bcl-1 locus, and the key oncogene
of bcl-1 locus in PRAD1/cyclin D1 gene that encodes the protein regarding cell
cycle. Recently, several studies using immunohistochemical and molecular methods
have demonstrated the overexpression of cyclin D1 mRNA/protein in cases of MCL.
We have studied immunohistochemical expression of cyclin D1 protein on frozen
sections of 27 cases of MCLs and evaluated the relationship between the
expression of cyclin D1 and prognosis. Sixteen (59.3%) cases showed intranuclear
staining of cyclin D1 protein and 6 of 7 cases examined using RT-PCR methods
showed the overexpression of PRAD1/cyclin D1 mRNA. The data indicate that
intranuclear staining of cyclin D1 protein is associated with the overexpression
of PRAD1/cyclin D1 mRNA. The survival time of cyclin-D1 positive group was
shorter than that of cyclin D1-negative group, and there was a significant
difference in survival time between the two groups (p < 0.05; log-rank test).
These data suggest that the MCLs with overexpression of PRAD1/cyclin D1 protein
has poor prognosis, and intranuclear expression of cyclin D1 protein is a useful
prognostic marker for MCL.
PMID- 9640845
TI - Substances reactive with mannose-binding protein (MBP) in sera of patients with
rheumatoid arthritis.
AB - OBJECTIVES: In order to evaluate the role of mannose-binding protein (MBP) in
rheumatoid arthritis, we characterized MBP-binding substances in sera of patients
with this disease. METHODS: An enzyme linked immunosorbent assay (ELISA) was used
to detect MBP-binding substances in sera of patients with RA. We applied the sera
of two RA patients to an immobilized MBP column, and by means of both ELISA and
molecular sieve chromatography, examined the substances that bound to MBP. MBP
MASP complexes were added to the fractions containing the binding substances, and
C4-consuming activity was examined. RESULTS: Sera of patients with RA showed
stronger MBP binding on ELISA than did those of normal controls. In the case of
RA sera, both IgG was IgM-RF eluted from the MBP column, whereas with normal
controls, only IgG was obtained. The results of molecular sieve chromatography
showed that the binding substances of RA patients consisted of immune complexes
containing IgG and IgM-RF. These substances were specifically bound to MBP, and
once bound, the MBP-MASP complexes were then able to consume C4. CONCLUSION: MBP
binds to immune complexes consisting of IgG and IgM-RF, and probably recognizes
either the mannose moiety of IgM-RF or the N-acetyl-glucosamine of agalactosyl
IgG. When this occurs in RA patients, the lectin pathway would then be activated.
PMID- 9640846
TI - A case of retroperitoneal abscess: an unusual complication of cholecystitis and
choledocholithiasis.
AB - A man, 73 years old, who developed acute biliary tract infection complicated with
retroperitoneal abscess formation in iliopsoas region was reported. The magnetic
resonance imaging was especially effective to delineate the lesion, extending
from the subhepatic down to the iliopsoas muscle. The echo-guided fine needle
aspiration technique was successful to make the lesion subside.
PMID- 9640847
TI - Frequency of grandparent contact with grandchild sets: six factors that make a
difference.
AB - Using data from the second wave of the National Survey of Families and
Households, the authors examine the determinants of frequent and infrequent
visiting between grandparents and their grandchild sets. A grandchild set
consists of all the children of a particular child of the grandparent, provided
that the grandchildren reside in their parent's household. The 6 significant
predictors of frequent or infrequent contact are geographic distance, quality of
relationship between grandparent and parent of the grandchild set, number of
grandchild sets, gender of grandparent, lineage of the grandchild set, and
marital status of the grandparent.
PMID- 9640848
TI - Constant hierarchic patterns of physical functioning across seven populations in
five countries.
AB - This research was aimed at identifying critical steps in the decline in physical
function that often parallels aging. Six basic and nine instrumental activities
of daily living (ADLs) were classified into four domains of disability
characterized by specific underlying physical impairment. The hierarchical order
of this classification was verified in two random samples representative of the
older home-dwelling population. The concordance level of disability and results
of performance-based measures of physical function were also tested. Finally, the
cross-cultural reliability of the model was verified in seven population-based
samples of older persons living in five European countries. In older persons the
disabling process follows a general pattern of progression based on a typical
sequence of impairments.
PMID- 9640849
TI - Recruiting research participants: a comparison of the costs and effectiveness of
five recruitment strategies.
AB - Among the major costs associated with conducting survey research are the time and
money spent recruiting a large and racially representative sample. Contrasted
here are the costs of different recruitment strategies (agencies, support groups,
snowballs, media, mass mailings) in terms of project time, supplies (e.g.,
postage, support materials), and staff time as they bear on the costs of
recruiting 841 older mothers of offspring with lifelong disabilities. Results
indicate that the costs of recruitment vary by method and race. Whereas agencies,
support groups, and snowball recruitment were low- to moderate-cost strategies,
they were less effective for recruiting African Americans than were media and
demographic sampling unit strategies. These analyses suggest that with
appropriate planning, funding, and implementation, nonprobability sampling
methods can be used successfully to recruit a large and diverse sample.
Suggestions for improving the implementation of future recruitment campaigns are
also offered.
PMID- 9640850
TI - Satisfaction with outpatient geriatric evaluation and management (GEM).
AB - The purpose of this study was to evaluate high-risk older adults' satisfaction
with outpatient geriatric evaluation and management (GEM). Community-dwelling
Medicare beneficiaries (n = 522) age 70 years and older who had a high
probability of repeated admission to hospitals (Pra > .40) were randomly assigned
to receive either usual care or GEM for six months. Despite the stresses imposed
by outpatient GEM (e.g., new relationships with providers, frequent office visits
and changes in treatments), the mean satisfaction scores of the recipients of GEM
were 9% higher than those of the recipients of usual care (4.31 vs 3.96, p <
.001). The primary physicians of GEM recipients were also highly satisfied with
GEM care.
PMID- 9640851
TI - Awareness and utilization of community long-term care services by elderly Korean
and non-Hispanic white Americans.
AB - This article presents a comparative analysis of the level of awareness and
utilization of 15 community-based long-term care services by 213 elderly Korean
and 201 non-Hispanic White Americans. We found extremely low levels of awareness
and utilization of long-term health and social services among Korean Americans,
in both absolute and relative terms. This finding challenges the success of the
Older Americans Act, an important funding source of those services, in meeting
its stated objectives to increase service availability and delivery to minority
elders and socioeconomically disadvantaged elders. Strategies for effective
outreach and public education efforts are also discussed.
PMID- 9640852
TI - Profiles of hospital, physician, and home health service use by older persons in
rural areas.
AB - Using data from the Medicare Current Beneficiary Survey, we identify differences
in hospital days, home health visits and physician office visits across five
geographical categories. After controlling for individual characteristics and
availability of health care providers, we find significant differences in service
use. Results show greater use of home health care and less use of physician
office visits and hospital care in rural areas. Because service use exhibits
patterns of substitution and complementarity, future research on the use of
health services needs to move beyond modeling the use of single services to
modeling the range of services used.
PMID- 9640853
TI - The impact of female caregivers' employment status on patterns of formal and
informal eldercare.
AB - This article uses data from the 1989 National Long-Term Care Survey and its
companion Informal Caregivers Survey to investigate how the employment of female
primary caregivers (FPCGs) affects hours of care received by disabled elderly
care recipients (CRs). Multivariage analyses controlling for key FPCG and CR
characteristics indicate that when FPCGs are employed they provide significantly
fewer hours of care personally; however, their CRs also receive significantly
more hours of help from other sources. When FPCGs work more than 17 hours per
week, their CRs receive significantly fewer total weekly hours of care than would
otherwise be the case.
PMID- 9640854
TI - Listening to caregiving sons: misunderstood realities.
AB - In-depth interviews with 30 sons actively involved in caring for a parent with
dementia expand the understanding of sons' caregiving experiences. The within
group analysis revealed common themes that emerged from the narratives--duty,
acceptance, taking charge, common emotions, and work flexibility--as well as
common issues--loss, sibling relationships, role reversal, coping strategies, and
positive outcomes. The interviews also generated a typology of son caregivers
that included such types as the dutiful son, the son who goes the extra mile, the
strategic planner, and the son who shares the care.
PMID- 9640855
TI - Interracial and intraracial differences in neuropsychiatric symptoms,
sociodemography, and treatment among nursing home patients with dementia.
AB - Using an adaptation of George's (1989) social antecedent model of
psychopathology, this article examines interracial and intraracial differences in
neuropsychiatric symptoms, sociodemography, and treatment among nursing home
patients with dementia. The final sample consisted of 164 U.S.-born African
Americans, 54 African Caribbeans, and 68 Caucasians. Although there were
appreciable interracial differences in sociodemographics, there were minimal
clinical differences. This finding may reflect both racial differences in
pathways to institutionalization and the homogenization of clinical
characteristics created by new governmental standards for nursing homes. There
were no substantial differences between African Americans and African Caribbeans.
Use of medication to treat neuropsychiatric symptoms was low, and may have
reflected difficulties in diagnosis and concerns about the abuse of medications.
PMID- 9640856
TI - Retention of administrators in nursing homes: what can management do?
AB - Annual turnover among nursing home administrators may be 40% or higher. To
investigate the factors that could lead to greater administrator retention,
responses to a survey (53% response rate) were analyzed using factor analysis and
multiple regression models. Results show that higher retention is observed when
administrators are allowed to function independently, are involved in decision
making, are treated fairly, and are given reasonable goals to achieve.
Organizations must hire administrators whose values match theirs. Multifacility
chain organizations and for-profit facilities appear to have a greater need to
embrace organizational principles that lead to greater job satisfaction.
PMID- 9640857
TI - In their own words: nursing assistants' perceptions of barriers to implementation
of prompted voiding in long-term care.
AB - Prompted voiding is an effective intervention for the improvement of continence
in long-term care. This study investigated certified nursing assistants' (CNAs)
perceptions of incontinence etiologies, as well as perceived barriers to prompted
voiding implementation. A questionnaire was administered to CNAs in 23 long-term
care facilities. Data analysis was conducted using descriptive statistics and
correspondence analysis. CNAs perceived prompted voiding as helpful; however,
inadequate staffing, workload, and turnover/absenteeism hindered implementation.
CNA recommendations for long-term success included increased staff, staff
support, improved communication, ongoing education, and alternative delivery
models of care.
PMID- 9640858
TI - Teaching and maintaining behavior management skills with nursing assistants in a
nursing home.
AB - This article describes a nursing staff training program in basic behavior
management skills and a formal staff management system to encourage the
application of these basic skills on the nursing unit. Behavioral skills training
consists of a 5-hour in-service followed by three weeks of on-the-job training to
ensure accurate application of behavior management skills. Following training, a
staff management system is used to facilitate long-term use of the skills.
Components of the staff management system include supervisory monitoring of the
nursing assistants (NAs) by licensed practical nurses (LPNs), NA self-monitoring,
verbal and written performance feedback, and incentives.
PMID- 9640859
TI - [Antepartum amniotic fluid index and pregnancy outcome].
AB - Our purpose was to evaluate prognostic value of antepartum amniotic fluid index
(AFI) on fetal and newborn outcome, because oligohydramnion is associated with
increased risk of fetal and newborn distress. Perinatal outcome was defined by 1'
and 5' Apgar score, intrapartum fetal heart rate (FHR), blood gas, acid-base
status in umbilical artery, mode of delivery and meconium-stained amniotic fluid.
Data was analysed with CSS Statistica for Windows package by test t for
independent samples and chi 2. Prospective observations was conducted with 84
singleton pregnancies complicated by oligohydramnion (AFI < or = 5 cm). A 336
pregnant women, with normal amniotic fluid index and no complicated pregnancy,
was considered as controls. No increased operative delivery and meconium-stained
amniotic fluid rate was noted. There was no significant effects AFI on blood
gases in umbilical artery and Apgar score. Oligohydramnion was associated with
increased risk of fetal acidosis (pH < 7.16) (p = 0.009) and abnormalities of FHR
(variable decelerations) (p = 0.004). Reduced AFI had poor predictive value of
fetal acidosis and newborn depression positive predictive value (8-13%).
Summarizing the results, our investigation showed that amniotic fluid index is
only one point in the prognosis of perinatal outcome.
PMID- 9640860
TI - [Salt taste perception in women during physiological pregnancy].
AB - The authors studied a sensory intensity response to sodium chloride (NaCl) and a
sensory hedonic response to salt in suprathreshold concentrations in 120 healthy
primigravidas (age: 20-40) during three trimesters of physiological pregnancy,
and in 22 healthy nonpregnant women of the same age examined on the 7th or 8th
day of the menstrual cycle. In all the periods covered by the study, pregnant
women have manifested a tendency to a lower intensity response to all
concentrations in comparison with nonpregnant women. The weakening of the
response has become statistically significant in the second trimester--with
respect to low concentrations, and at the final stage of pregnancy--with respect
to medium concentrations. The sensory hedonic response in pregnant women has been
increasing along with the age of the fetus. In comparison with the response of
nonpregnant women, pregnant women have shown a tendency to the intensified
response in all the periods covered by the study.
PMID- 9640861
TI - [Diagnosis of human parvovirus B19 infection in nonimmune hydrops fetalis].
AB - Parvovirus B19 (PV B19) infection was investigated in 29 pregnant women with
fetal hydrops, after exclusion of feto-maternal incompatibility within red blood
cell antigens, TORCH infections, feto-maternal hemorrhage and genetics reasons.
The active viral infection was detected in 9 women (31%) by PCR amplification of
DNA B19; in 2 of them IgM and IgG, in 1 IgM and in 4 IgG antibodies were also
present. In 6 women (20%) IgG antibodies were only found, but not IgM and DNA
B19, which confirmed infection in the past. In addition in 9 cases DNA B19 was
evaluated in the fetal blood. The results in the mothers and their fetuses were
concordant (4 positive, 5 negative). Our conclusion is that in nonimmune hydrops
fetalis, PV B19 infection should be based on the viral DNA evaluation in the
blood of mother (or fetus). IgM antibodies, in time of fetal disorders, might not
be detected.
PMID- 9640862
TI - [Flow cytometric analysis of cord blood lymphocytes].
AB - It has been observed that immunological reactivity of neonatal leukocytes is
diminished. It seems to result from lymphocytes immaturity. In the present study
we have evaluated the phenotype of cord blood lymphocytes with the use of flow
cytometry. In neonates we have observed the increase in the absolute number of
CD1a and CD7 positive lymphocytes as well as CD2, CD3, CD4, CD8, CD16, CD19 and
CD20 positive, while number of CD57 positive cells was significantly decreased.
The ratios of CD4/CD8 and T/B lymphocytes were similar to the corresponding
ratios observed in adults. Our results have shown the presence of immature
lymphocyte population as well quantitative depletion of subpopulation of CD57
cells, what may pose an increased risk of infection in neonates. Nevertheless,
increased number of T and B lymphocytes with mature phenotype along with normal
ratio of lymphocyte subpopulations and increased number of CD16 positive cells
(NK cells), may explain phenomenon of good health among majority of newborns.
PMID- 9640863
TI - [Adenoid cystic carcinoma of the breast. Analysis of 7 patients].
AB - A retrospective analysis of 7 patients with adenoid cystic carcinoma of the
breast operated at Center of Oncology in Krakow is presented. Ten years without
evidence of disease survived 6 (85.7%) patients. One patient only, with poorly
differentiated carcinoma, presented axillary metastases and died of metastases to
the lungs and hepar.
PMID- 9640864
TI - [Dependence of serous activity of cathepsin B on histological types of ovarian
carcinomas].
AB - The preoperative activity of cathepsin B was determined in the serum of 110
patients with primary ovarian carcinomas and in 35 women with benign ovarian
tumor. The significant increase of cathepsin B activity in ovarian carcinomas is
independent of its types in comparison to benign ovarian tumor. The percentage of
the results with value above the cut-off values was the highest for serous types
of ovarian carcinomas. The dependence between the increase of cathepsin B
activity and the FIGO stage of the disease was observed only for serous and
endometrioid type of ovarian carcinomas.
PMID- 9640865
TI - [Results of surgical treatment of vulvar cancer].
AB - OBJECTIVES: Vulvar cancer is a relatively rare genital malignancy. The mainstay
of it's treatment is surgery. DESIGN: A retrospective study of vulvar cancer
patients treated between 1967 and 1995 at Department of Gynaecology, Medical
University of Gdansk. MATERIALS AND METHODS: The type and outcome of surgical
treatment was studied in 162 consecutive patients. RESULTS: The surgery was
limited to the vulva in 24% cases and in the reaming 76% of patients removed were
also regional lymph nodes. Median survived of the whole group was 105 months and
actuarial 5-year survival-60%. CONCLUSIONS: The results of treatment of vulvar
cancer in presented series correspond well with the literature data.
PMID- 9640866
TI - [Familial complex chromosome translocation of t(1;4;10)(q21.3;q27;q26.1) verified
by FISH].
AB - The inheritance complex chromosome translocation is a rare. A familial complex
chromosome rearrangement t(1;4;10)(q21.3;q27;q26.1) involving three chromosomes
ascertained due to four spontaneous abortions in phenotypically normal childless
woman there is presented. Cytogenetic analysis according to classic banding
techniques were verified by fluorescent in situ hybridization (FISH) technique.
PMID- 9640867
TI - [The repeated ignoring of prenatal care by a pregnant woman after kidney
transplantation].
AB - A multipara after kidney transplantation who had for the second time completely
neglected prenatal care was admitted to a delivery room at the end of the first
stage of labour. She delivered a daughter, weight 2900 g, Apgar 9 points.
Mother's puerperium was without complications. The transient oliguria occurred in
the baby on the second day. The problems connected with pregnancy after kidney
transplantation were discussed.
PMID- 9640868
TI - [The case of intrauterine pregnancy coexisting with extrauterine pregnancy which
was surgically removed].
AB - The case of simultaneous intrauterine and ruptured ectopic pregnancy was
presented. The diagnosis of coexisting intrauterine and ectopic pregnancies is
difficult. The patient was admitted to the clinic because of abdominal pain and
vaginal bleeding in the 10th week of pregnancy has been treated by laparotomy.
The intrauterine pregnancy was continued successfully to term. The importance of
careful sonographic examination of adnexal region was stressed in all symptomatic
patients with first trimester pregnancy.
PMID- 9640869
TI - [Intrauterine growth retardation (IUGR) vs small for gestational age fetus (SGA).
Diagnostic aspects].
AB - Fetal growth deficiency and low birthweight requires an accurate assessment and
may be divided into two groups: 1. Intrauterine growth retardation (IUGR) which
is strongly associated with a fetal structural malformation, infections (TORCH)
and utreoplacental dysfunction considered to be the most common cause. 2.
Genetically, constitutionally small baby (SGA) classified as a well-nourished,
healthy and short baby. Taking into account clinical data, medical history,
health state of a patient, serial ultrasound growth scan, Doppler ultrasound,
cardiotocography and enzymatic monitoring may proved to be useful to
differentiate between these two problems.
PMID- 9640870
TI - Calcium hydroxyapatite deposition disease of the neck: finding in three patients.
AB - Calcium hydroxyapatite deposition disease may occasionally involve the
superolateral portion of the longus colli muscle. Clinical symptoms include
headache, neck pain, and dysphagia. Characteristic prevertebral calcifications
with the epicenter at the C1-C2 level are depicted on lateral radiographs of the
cervical spine.
PMID- 9640871
TI - [Computed tomographic diagnosis of biliary ileus].
AB - Rare in the general population, gallstone ileus accounts for 25 per cent of
nonstrangulated small bowel obstructions in patients over the age of 65. While
mortality has declined over the years, it remains high at 12-17 per cent. This is
largely due to the insidious symptoms making the diagnosis difficult and to the
aged patient population, with frequent comorbid medical conditions contributing
to mortality. Much better than plain radiograph and probably easier than
ultrasound, CT makes the correct diagnosis of the classical triad of Rigler:
distended small bowel loops, pneumobilia and an ectopic calcified gallstone. We
report two cases promptly and specifically diagnosed with CT. The second case was
a very rare Bouveret's Syndrome, a gastric outlet obstruction caused by a
gallstone. Patients were treated by a one time associated enterolithotomy and
cholecystectomy. We recommend the early use of abdominal CT scanning for the
investigation of clinical bowel obstruction in the elderly, where gallstone ileus
is a more common condition.
PMID- 9640872
TI - Giant fibrovascular polyp of the esophagus.
AB - We report on a patient who presented a fibrovascular polyp of the esophagus,
which is an uncommon submucosal tumor that can attain giant proportions. It is
covered with squamous epithelium and consists of a mixture of myxoid-collagenous
fibrous elements, vascular structures and adipose cells. Diagnosis is made via
upper endoscopy, echoendosonography and barium studies. CT and MR imaging can be
helpful for full evaluation of this rare lesion.
PMID- 9640873
TI - Glenoid dysplasia: radiographic and CT arthrographic findings.
AB - A 60-year-old man with dysplasia of the glenoid and a rotator cuff tear is
reported on. Because of the tear, CT arthrography was performed, offering an
opportunity to evaluate the various soft tissue abnormalities accompanying
glenoid dysplasia. Marked thickening of the glenoid cartilage and labrum was
apparent, as well as an abnormal posterolateral orientation of the glenoid
cavity. A deep notch was observed along the central portion of the glenoid
cartilage. Furthermore the middle glenohumeral ligament appeared thickened and
cordlike.
PMID- 9640874
TI - Chronic recurrent multifocal osteomyelitis.
AB - The case of a 17-year-old boy with Chronic Recurrent Multifocal Osteomyelitis
(CRMO) is presented. Clinical manifestations included a three month history of
marked antalgic scoliosis, thoracic and mid-sternal pain, mild fever, elevated
erythrocyte sedimentation rate, and skin lesions such as acne and psoriasis.
Radiologically, osteolytic lesions were seen in the sternum and the thoracic
spine. Histopathological examination of the sternal lesion revealed chronic
osteomyelitis. Bone cultures of the resected specimen were negative for known
pathogens. The combination of the clinical, radiological, histopathological and
microbiological features was the clue to the diagnosis of CRMO.
PMID- 9640875
TI - Temporal lobe abscess as a complication of cholesteatoma: sequential radiological
findings.
AB - Temporal lobe abscess is a rare but known complication of petrosal bone
cholesteatoma. We present a case with clinical history, diagnostic imaging and
sequential radiological findings of the abscess from the early temporal
cerebritis phase till the late full encapsulated abscess. We also succeeded in
visualizing the fistula through the tegmen tympani on MR-images.
PMID- 9640876
TI - CT findings in splenic tuberculosis.
AB - Splenic tuberculosis is rare and delay in diagnosis is common. We present two
cases of splenic tuberculosis with their appearance on CT. The CT findings were
multiple, round or ovoid, low-density lesions without calcification. Except for
non-specific lymphadenopathy no abnormality nor history suggestive of
tuberculosis was revealed prior to laparotomy. Although CT does not confirm a
diagnosis of splenic tuberculosis, it would be a valuable examination to define
the extent of disease and guide aspiration biopsy.
PMID- 9640877
TI - [Screening for breast cancer: the time of decision].
AB - The purpose of this review article is to propose the basic rules of a
scientifically correct breast cancer mass screening. It might give to the
different authorities arguments to make a choice between an organized screening
and some trials currently used in our country.
PMID- 9640878
TI - Chronic critical limb ischemia: what is the benefit of radiological intervention?
Indications and results.
AB - Indications of interventional radiological procedures in patients with chronic
critical limb ischemia are not clearly defined. PTA of limb arteries is used only
in 3 of 4% of patients, although 20 to 40% might be candidates for a proximal
intervention in the iliac arteries. Following PTA of intrapopliteal arteries,
limb salvage varies from 56 to 82% and arterial patency rate from 34 to 100%
after 1 to 2 years follow-up in non controlled case series studies. Arterial
local thrombolysis shows better results than surgery in subgroups of patients in
a few studies. Pulse spray technique does not show better clinical results than
conventional infusion of the plasminogen activator. Overall, radiological
interventions give similar results compared with surgery, concerning limb salvage
rate, length of hospital stay, morbidity and mortality, but significantly more
patients are discharged home versus a nursing institution after radiological
treatment than after surgery. Radiological techniques seem to be cost effective
compared to surgery. Amputation should be carried out only after all
revascularization possibilities have been ruled out at a multidisciplinary
vascular center.
PMID- 9640879
TI - [Gastric diverticulum simulating a left adrenal mass].
PMID- 9640880
TI - Permeability barrier abnormality of hairless mouse epidermis after topical
corticosteroid: characterization of stratum corneum lipids by ruthenium tetroxide
staining and high-performance thin-layer chromatography.
AB - Topical corticosteroids (TCS) are among the most frequently used topical
therapeutics. Recently, it has been shown that TCS not only has antiproliferative
actions, but also inhibits the differentiation of the epidermis and finally
perturbates stratum corneum (s.c.) barrier function. It is well established that
epidermal barrier function resides within the intercellular lipids of the SC.
However, to date, little is known about the effects of TCS on the structure and
composition of s.c. lipids. We therefore used hairless mouse skin to study the
sequential changes of the s.c. permeability barrier and their intercellular
lipids by ruthenium tetroxide staining and high-performance thin-layer
chromatography (HPTLC) during topical use of corticosteroids. The results
demonstrated a progressive increase in transepidermal water loss accompanied by a
diminution in the SC intercellular lipid lamellae, which showed a normal
structure of individual lamella. Analysis of lipid composition by HPTLC after a 6
week application of TCS also showed an obvious decrease in all the main
components of s.c. lipids, which are known to constitute the permeability barrier
of the skin. In light of these results, our work provides direct morphological
evidence that TCS deteriorates the permeability barrier of epidermis when applied
to normal skin.
PMID- 9640881
TI - A preliminary study aimed at the detection of Leishmania parasites in subjects
with cutaneous leishmaniasis using polymerase chain reaction.
AB - As a basic study for future diagnosis of cutaneous leishmaniasis, we tried to
detect Leishmania parasites representing different species in the subgenera
Leishmania and Viannia from subject patients with cutaneous leishmaniasis by
using the polymerase chain reaction (PCR) with the subgenus Viannia specific
primer. Four out of the 14 specimens revealed an amplified DNA of 70 bp specific
for the subgenus Viannia (L. braziliensis complex). No bands were detected in the
rest of the specimens belonging to the subgenus Leishmania and unclassified
groups. The base sequences of the amplified DNA corresponded with those of the L.
(V). braziliensis kinetoplast minicircle. We concluded that PCR using the present
primer specific for the subgenus Viannia would be useful in detecting Leishmania
parasites in lesions of cutaneous leishmaniasis caused by the L. braziliensis
complex.
PMID- 9640882
TI - Topical PUVA therapy for chronic hand eczema.
AB - Seventeen patients with persistent chronic hand eczema were treated with topical
0.1% 8-methoxypsoralen and UVA (PUVA) for 8 weeks. Significant improvement was
achieved in 5 cases (29%), moderate improvement in 9 (53%), and little
improvement in 3 (18%). The mean number of PUVA treatments was 22.2, and the mean
total UVA dose was 63.5 J/cm2. There was no association between clinical response
and duration of hand eczema, positive patch test reaction, or atopic status.
Since topical PUVA has no risk of systemic side effects, it should be considered
as an alternative treatment for patients with chronic hand eczema who are
resistant to other topical medications.
PMID- 9640883
TI - Membranous and soluble forms of Fas antigen in cutaneous lupus erythematosus.
AB - The role of Fas-mediated apoptosis in cutaneous lupus erythematosus (LE) is still
unclear, although the Fas/FasL system has been investigated in autoimmune
diseases in relation to impaired apoptosis. In order to elucidate the connections
between acute cutaneous LE (ACLE) and chronic cutaneous LE (CCLE), we determined
the expression of membranous Fas antigen (mFas) on peripheral blood mononuclear
cells (PBMC) by flow cytometry and the levels of the soluble form of the Fas
antigen (sFas) in sera. The ratio and the mean fluorescence intensity of mFas
were much higher in ACLE patients than in others, including patients with CCLE
and atopic dermatitis and normal healthy controls. The levels of sFas in ACLE and
CCLE patients were also elevated, and there was a significant increase in sFas
levels in ACLE patients over that in CCLE patients. Immunohistochemical studies
revealed that Fas antigen was predominantly expressed on infiltrating cells
around blood vessels and appendages in ACLE and CCLE patients. Based on these
findings, it is suggested that the expression of Fas antigen is closely
associated with the activation of circulating lymphocytes, especially in ACLE
patients, but is not directly associated with keratinocyte damage.
PMID- 9640884
TI - Treatment of molluscum contagiosum in males with an analog of imiquimod 1% in
cream: a placebo-controlled, double-blind study.
AB - The objective of this double-blind, placebo-controlled study was to evaluate in
males the clinical efficacy in treating molluscum contagiosum and tolerance of an
analog of imiquimod (1%) in cream. One hundred patients between 9 and 27 years of
age (mean 16.3), with 733 lesions (mean 7.3), whose size ranged from 2 to 5 mm
diameter (mean spot size 3.4 mm) and a biopsy-confirmed diagnosis of molluscum
contagiosum were randomized into two parallel groups. In a double-blind manner,
precoded 40-g tubes were dispensed. Patients self-administered the trial
medication to their lesions at home three times daily for five consecutive days
per week. The study was scheduled with 4 weeks of active treatment (maximum 60
topical applications) and 12 months (on a monthly basis) of follow-up. Patients
were examined on a weekly basis. Thirteen patients had atopic dermatitis. A
clinically and histopathologically confirmed total elimination of lesions was
considered as cured. After four weeks of treatment, 49 patients and 372 lesions
were cured. Breaking the code revealed that imiquimod cream had cured 82% of the
patients and 86.3% of the lesions. Placebo cleared 16% of the patients and 63 of
the lesions (p < 0.0001). During the treatment, 88% of the patients experienced
no allergic, localized, or drug-related adverse symptoms. Twelve patients,
predominantly in the imiquimod cream group reported non-objective, drug-induced,
mild reactions with no dropouts. The study was followed-up for 12 months. Among
49 cured patients, 3 had relapses after 10 months. In conclusion, the study
demonstrated that 1% imiquimod analog in cream with mild subjective side effects
is significantly more efficacious than the placebo in curing molluscum
contagiosum in males.
PMID- 9640885
TI - Sarcomatoid carcinoma of the skin: report of a case.
AB - We report the histological, immunohistochemical and ultrastructural findings of
an exophytic cutaneous tumor composed of a mixture of typical basal cell
carcinoma (BCC) and malignant fibrous histiocytoma. Nine previously reported
carcinosarcomas of the skin are reviewed. We prefer the term "sarcomatoid
carcinoma" for this rare neoplasm. Only the BCC showed a positive immunoreaction
to cytokeratin; the sarcomatous component was negative, but it did express
vimentin, and, focally, smooth-muscle-specific actin and KP1 (CD68). Both
components showed p53 immunostaining.
PMID- 9640886
TI - Diagnostic pitfalls of Merkel cell carcinoma and dramatic response to
chemotherapy.
AB - Merkel cell carcinoma (MCC) is an unusual malignant tumor that arises from
neuroendocrine cells with features of epithelial differentiation. We describe a
MCC patient with unusual clinical, histopathological, and immunohistochemical
features. Although the microscopic, immunohistochemical, and ultrastructural
characteristics of MCC have been well defined, diagnostic difficulties remain,
particularly in distinguishing it from lymphoma involving the skin, as suggested
by our case. This is an unusual case in which dense lymphoid infiltration masked
the true tumor. All the immunohistochemical markers of MCC except neuron-specific
enolase (NSE) were negative. The dramatic response to primary chemotherapy was
also very noteworthy.
PMID- 9640887
TI - A case of rudimentary meningocele.
AB - A 2-year-old girl had an alopecic, atrophied macule on the midline of the
occipital area. X-ray and CT scan of the scalp revealed no underlying bone
defect. Histologically, the whole dermis and subcutis showed dense, hyalinized
collagen bundles intermingled with cuboidal, epithelioid cells that surrounded
pseudovascular spaces or gathered in clusters. These flattened or cuboidal cells
were positive for anti-vimentin antibody; some of them were also positive for an
anti-epithelial membrane antigen antibody, but negative for antifactor VIII
related antigen and Ulex europaeus I lectin.
PMID- 9640888
TI - Intralymphatic embolic cells with cutaneous endometriosis in the umbilicus.
AB - Endometriosis is defined as the presence of both functioning endometrial glands
and stroma outside their usual location lining the uterine cavity. It has been
identified in virtually all tissues and organs of the female body with the
exception of the spleen. There have been many theories proposed regarding the
etiology and pathogenesis of endometriosis. One is the transport of cells through
lymphatics and blood vessels. A 44-year-old female suffering from an episode of
endometriosis of the umbilicus, left inguinal, uterus, and bilateral ovaries in
association with a Mullerian anomaly is presented. Histopathological findings of
a skin biopsy from her umbilicus showed aggregated cells within the lymphatic
vessel of the upper dermis. This case provides evidence suggesting that cutaneous
endometriosis could occur by transport of endometrial cells through lymphatics or
blood vessels.
PMID- 9640889
TI - Superficial spreading melanoma arising in a longstanding melanocytic nevus on the
sole.
AB - In Asians, the plantar surface is the commonest site for cutaneous melanoma, and
most melanomas arising in this region are the acral lentiginous type. Herein we
describe a rare case of superficial spreading melanoma arising in a longstanding
melanocytic nevus on the sole of a Korean.
PMID- 9640890
TI - Leopard syndrome: a tropical rarity.
AB - This is a case report of a classical presentation of the Leopard syndrome from
the Indian subcontinent. The male patient had progressively increasing
generalised multiple lentiginosis, ocular hypertelorism, pulmonary stenosis,
short stature, cryptorchidism, and pectus excavatum. The case is documented for
its rarity in this part of the world and typical clinical presentation.
PMID- 9640891
TI - Gigantic pyoderma gangrenosum.
AB - A 71-year-old Japanese female with gigantic pyoderma gangrenosum is reported. The
pyoderma lesions had been treated as an infectious condition for seventeen months
and had extended to enormously large areas. The nature of the chronic type of
pyoderma gangrenosum may need to be stressed, even for dermatologists.
PMID- 9640892
TI - Recurrent herpes zoster.
PMID- 9640893
TI - Association of psoriasis vulgaris with Sjogren's syndrome.
PMID- 9640894
TI - Effects of televised safety models on children's risk taking and hazard
identification.
AB - OBJECTIVE: To examine effects of televised safety models on children's
willingness to take physical risks and their ability to identify injury hazards
in common situations. METHODS: Sixty children, between the ages of five and eight
years, were exposed to one of three TV stimulus programs: (1) a safety
educational videotape, in which actors engaged in dangerous behavior, suffered
injuries, and then enacted alternative safe behaviors; (2) an animated cartoon,
which portrayed characters engaged in safety behaviors incidental to the main
story line; or (3) the same cartoon program edited to omit the scenes depicting
safety behavior. Children's willingness to take physical risks was measured
before and after the TV stimulus by a series of pictorial child-relevant
scenarios in which they could indicate the level of risk they would take. They
also completed pretest and posttest measures of hazard identification, in which
they were to identify injury hazards in several pictorial scenarios. RESULTS:
Exposure to the safety educational videotape decreased children's willingness to
take physical risks and increased their identification of injury hazards.
Exposure to the animated cartoon with incidental safety components did not affect
risk taking, but did increase ability to identify hazards. CONCLUSIONS: Findings
are interpreted as evidence of observational learning and priming of thematically
related knowledge by the television stimuli. Implications for safety educational
curricula are discussed.
PMID- 9640895
TI - Commentary: television, children's health and safety behavior, and pediatric
psychology.
PMID- 9640896
TI - Social functioning of children surviving bone marrow transplantation.
AB - OBJECTIVE: To evaluate the behavioral reputation and peer acceptance of pediatric
bone marrow transplant (BMT) survivors. METHODS: Forty-eight BMT survivors (8-16
years of age) were compared to 48 nonchronically ill, same-classroom, same-gender
comparison peers (COMP). Peer, teacher, and self-report data were collected.
RESULTS: Relative to COMP, BMT survivors had fewer friends and were described by
peers, but not teacher or self-report, as more socially isolated. In addition,
peers described BMT survivors as being less physically attractive and
athletically skilled. Further analyses suggested that these nonsocial attributes
(physical appearance and athletic ability) and treatment variables (whether
cranial irradiation was received) mediated the social difficulties of BMT
survivors. CONCLUSIONS: These data are suggestive of an unremitting pattern of
difficulties with peers that has the potential to disrupt normal social and
emotional development. Differences between peer, teacher and self-reports
highlight the need for multiple informants in future work.
PMID- 9640897
TI - Behavior problems in children with diabetes: disentangling possible scoring
confounds on the Child Behavior Checklist.
AB - OBJECTIVE: The Child Behavior Checklist (CBCL; T. M. Achenbach, 1991), when used
to assess the behavior of children with diabetes, may contain confounds because
some behavioral items can have a physiologic etiology, and may skew reports of
behavioral disturbance. METHODS: Two techniques were used to disentangle possible
scoring confounds in the behavioral ratings of children with and without
diabetes: (1) the Somatic Complaints scale was deleted, or (2) Diabetes Items,
identified a priori with 89% agreement by nine medical personnel, were deleted.
RESULTS: As expected, with traditionally scored protocols, children with diabetes
obtained higher Internalizing and Total Behavior Problem scores than controls.
This group difference persisted whether the Somatic Complaints scale or the
Diabetes Items were deleted. CONCLUSIONS: Compared to controls, children with
diabetes obtained mildly elevated scores on six of the eight CBCL scales,
regardless of scoring method, suggesting that their mildly elevated behavioral
profile is not confounded by physiologic symptomatology.
PMID- 9640899
TI - Effects of maternal intelligence, marital status, income, and home environment on
cognitive development of low birthweight infants.
AB - OBJECTIVE: To examine direct and mediated effects of maternal IQ, marital status,
family income, and quality of the home environment on the cognitive development
of low birthweight infants. METHODS: Secondary analyses on a large dataset using
hierarchical regression identified factors correlated with cognitive outcomes in
children at 3 years of age who were born at low birthweight. RESULTS: Maternal IQ
was a critical variable, because it was highly correlated with child IQ and
because maternal intelligence influenced patterns of relationships among other
predictor variables including marital status, income level, and home environment
on child IQ. Analyses revealed that effects of these variables on child IQ
interacted with maternal IQ. CONCLUSIONS: Early childhood intervention programs
should target those low birthweight infants most at risk for impaired cognitive
development. Children at greatest risk are those living with unmarried, low IQ
mothers.
PMID- 9640898
TI - Concepts of illness in Icelandic children.
AB - OBJECTIVE: To investigate the development of illness concepts among healthy
Icelandic children. METHODS: Participants were 68 schoolchildren, 6-7, 10-11, and
14-15 years of age, and their parents. Cognitive developmental level and
understanding of physical illness were assessed within a Piagetian framework. In
addition, illness experience and illness behaviors (Child Illness Behavior
Questionnaire) were assessed. RESULTS: Results were consistent with previous
studies in that the development of illness concepts among Icelandic children was
consistent with Piaget's theory of cognitive development. No relation was found
between illness experience and understanding of illness. A more mature
understanding of illness was related to willingness to report the onset of
illness. CONCLUSIONS: The results suggest that findings from previous studies may
be generalized to a broader population.
PMID- 9640900
TI - Brief report: an intervention program for parents of pediatric cancer patients: a
randomized controlled trial.
AB - OBJECTIVE: To evaluate a psychoeducational intervention program for parents of
pediatric cancer patients, using cognitive and behavioral techniques. METHODS:
Parents were randomly assigned to an intervention (n = 39) and a control
condition (n = 42). Baseline assessment took place at diagnosis. Short-term
effects were measured immediately after the intervention, long-term effects six
months later. Control parents received standard care. Intervention parents
received, in addition, a manual-guided program during the first six months
following the diagnosis. RESULTS: With time all parents became significantly less
psychologically distressed. However, no between-group differences were noted in
psychological functioning, satisfaction with support, and intensity of emotions
immediately postintervention and six months later. CONCLUSIONS: Although the
clinical evaluation of the intervention was positive, it appeared that a
structured intervention program as described in this study was not any more
effective than standard care.
PMID- 9640901
TI - Consumer bill of rights ordered.
PMID- 9640902
TI - Acute aortic insufficiency.
PMID- 9640903
TI - The proposed tobacco settlement is not a good deal.
PMID- 9640904
TI - Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: the
Washington, DC, Dilated Cardiomyopathy Study.
AB - Although cardiac transplantation offers prolonged survival and improved quality
of life to patients with end-stage heart failure, many patients with idiopathic
dilated cardiomyopathy do not undergo this procedure. Possible barriers to
cardiac transplantation were examined among 138 patients with idiopathic dilated
cardiomyopathy from five hospitals in Washington, DC. Patients underwent follow
up for approximately 5 years. The patients or a close family member were
interviewed at baseline about socioeconomic factors and medical history. The
patients or their next-of-kin were recontacted at 1-year intervals to determine
patients' vital status and to obtain information about cardiac transplantation.
Overall, the cumulative survival at 12 and 60 months was 75.8% and 37.3%,
respectively. Only 3.6% (5 of 138) of the patients underwent cardiac
transplantation, and 19 (13.8%) patients had been placed on a waiting list for a
heart transplant. Black race and nonmarried status were inversely associated with
cardiac transplantation. Factors associated with not having been placed on a
waiting list included older age, lower income, and lack of private health
insurance. Black race was found to be significantly, but inversely associated
with cardiac transplantation while older age was inversely associated with having
been placed on a waiting list after adjusting for sex, race, education, and
private insurance. These findings suggest that black patients with idiopathic
dilated cardiomyopathy are less likely to undergo cardiac transplantation.
PMID- 9640905
TI - Physicians and nursing home care.
AB - Historically, physicians have not played a prominent role in the care of older
adults who reside in nursing homes. Physicians have been criticized for
abandoning their responsibilities to nursing home residents since the industry's
rapid growth in the 1960s, following the enactment of Medicare and Medicaid. As
many as 72% of private physicians do not go to nursing homes. This is true even
of those family doctors and internists whose practices are disproportionately
devoted to the elderly. Caring for institutionalized elderly patients over the
long term presents challenges that even physicians experienced with geriatric
patients in the community may find daunting. This study investigates reasons why
physicians in the Los Angeles area hesitate or refuse to see nursing home
patients.
PMID- 9640906
TI - The effectiveness of intermittent hyperbaric oxygen in relieving drug-induced HIV
associated neuropathy.
AB - This 3-month study evaluated the effects of hyperbaric oxygen on drug-induced
neuropathies in 22 patients with human immunodeficiency virus. All patients
included in the study had been taking an antiretroviral medication for at least
12 months and had subjective symptoms of numbness or tingling, lethargy, and a
decrease in deep tendon reflex. Patients with an active substance abuse history
or Kaposi's sarcoma were excluded. Of the 20 patients who completed the series,
17 had significant improvement, 2 had a demyelinating disorder that may have
affected the outcome, and 1 had no change.
PMID- 9640907
TI - Social support among African-American adults with diabetes. Part 1: Theoretical
framework.
AB - Diabetes mellitus affects African Americans in disproportionate numbers relative
to whites. Proper management of this disease is critical because of the increased
morbidity and mortality associated with poor diabetes management. The role of
social support in promoting diabetes management and improved glycemic control
among African Americans is a little-explored area. This article, the first in a
two-part series, provides a theoretical framework for examining the relationship
between social support and glycemic control among African-American adults.
PMID- 9640908
TI - A characterization of older AIDS patients in Maryland.
AB - This retrospective study evaluated Maryland acquired immunodeficiency syndrome
(AIDS) patients who were > or = 50 years at the time of AIDS diagnosis. All
patients diagnosed between January 1987 and June 1996 who were > 50 years were
included in the cohort. A total of 610 male (82.7%) and 128 female (17.3%) AIDS
patients aged > or = 50 were identified. The most common mode of human
immunodeficiency syndrome (HIV) transmission was male-to-male sexual contact
(34.7%). Additionally, 146 (19.8%) patients contracted HIV through blood
transfusions, 93 (12.1%) were infected through heterosexual contact, 134 (18.6)
were infected through i.v. drug abuse, and the remaining 109 (14.8%) had unknown
risk factors. Data from this preliminary study demonstrate that an alarming
percentage of AIDS patients (approximately 10%) in Maryland are aged > or = 50.
Sexual contact, either male-to-male or heterosexual transmission, was the route
of transmission for nearly 47% of this patient population. However, few research
projects, educational programs, or public health initiatives are specifically
targeted to this patient population. The increasing life expectancy of AIDS
patients as well as the advent of new drug treatments highlights the need for
further research to investigate the diagnosis and treatment of AIDS and HIV
infection among older patients.
PMID- 9640909
TI - Occult uterine rupture: role of ultrasonography.
AB - This article presents a case of occult spontaneous uterine rupture complicated by
pelvic infection and peritonitis in the postpartum period. Ultrasonography played
a primary role in the diagnosis of this complication and clearly demonstrated the
uterine wall defect. This finding was confirmed later by computed tomography and
by surgery.
PMID- 9640910
TI - Lincoln's last legacy: a narrative of the president's obscured autopsy
instruments.
PMID- 9640911
TI - [Angina pectoris is an expensive national disease. It requires a reasonable
distribution of responsibility between outpatient and inpatient care].
PMID- 9640912
TI - [Inadequate handling of stress is a risk factor in brain disease. Deviations in
stress levels can explain unfavourable prognosis].
PMID- 9640913
TI - [Anorexia--high priority in mass media, not in health care].
PMID- 9640914
TI - [Are Jews and Muslims in Sweden barbarians?].
PMID- 9640915
TI - [The link between exposure to mould and respiratory problems is
incontrovertible].
PMID- 9640916
TI - [The Kola peninsula: epidemics, high infant mortality, alcoholism...Hard reality
drains the very small resources of health care].
PMID- 9640917
TI - [How many X-ray examinations do patients tolerate? The National Institute of
Radiation Protection's conclusions on the level of knowledge].
PMID- 9640918
TI - [More strict Swedish rules on radiation protection. New directives from the EU
for health care].
PMID- 9640919
TI - [Documented effects of SSRI preparations in anxiety].
AB - The article consists in a review of the clinical evidence for treating anxiety
disorders with selective serotonin re-uptake inhibitors (SSRIs). Sufficient
documentation now exists to support the use of SSRIs in treating panic and
obsessive-compulsive disorders, and in Sweden moclobemide is now approved for use
in treating social phobia, and buspirone for use in treating generalised anxiety
disorder. Further documentation of the treatment of post-traumatic stress
disorder with SSRIs is probably to be expected. Benzodiazepines remain the most
commonly used anxiolytics. Although persistent adverse sexual reactions, and
withdrawal symptoms upon abrupt termination of medication, are notable side
effects of SSRIs, patients become measurably more self-confident and focused, and
manage risks more adequately. This underscores the need of further research into
the interrelationship of personality traits and anxiety symptoms.
PMID- 9640920
TI - [Forensic psychiatry in Vaxjo and Sundsvall: a new estimation method for unified
risk assessment].
PMID- 9640921
TI - [Rehabilitation and prevention. The patient himself actively works to reach the
targets].
PMID- 9640922
TI - [Gustaf Billqvist, a physician before his time: "Children must be comfortable in
hospital to recover!"].
PMID- 9640923
TI - [Plasma metanephrine measurements make the diagnosis of pheochromocytoma easier].
AB - A study where plasma metanephrine and normetanephrine concentrations in 51
patients with hypertension and 62 healthy normotensives were compared with those
in 52 patients with histologically confirmed phaeochromocytoma showed measurement
of the two variables to constitute a test that reliably excludes the presence of
phaeochromocytoma in cases where both values are normal. Other currently
available tests (e.g., plasma catecholamine assay) can yield false-negative
results in some patients with the tumour, and thus do not reliably exclude its
presence in unaffected patients. Accordingly, as a missed diagnosis can have
disastrous consequences for the patient, hitherto the exclusion of
phaeochromocytoma has typically entailed multiple and repeated tests which are
time-consuming and costly. The advantage of the plasma metanephrine
normetanephrine test is that, as it does not yield false-negative results, a
negative test result reliably excludes the presence of phaeochromocytoma in
suspected cases, and no further tests are necessary.
PMID- 9640924
TI - ["Alcolock"--an effective technique against traffic accidents].
PMID- 9640925
TI - [How does patient-oriented research work?].
PMID- 9640926
TI - [When the professional becomes personal. A tactful way to treat a sick
colleague].
PMID- 9640927
TI - [Inguinal hernia surgery deserves higher status. A new technique makes great
progress possible].
PMID- 9640928
TI - [Should general practitioners have possibility to become subspecialists?].
PMID- 9640929
TI - [Cost-effective use of drugs should be our goal].
PMID- 9640930
TI - [To compare hospital departments, a tactful procedure-- continuation].
PMID- 9640931
TI - [No conclusions can be drawn when the material is too small].
PMID- 9640932
TI - [Oral flora may be the cause of meningitis in lumbar puncture].
PMID- 9640933
TI - [Discussion about interventions performed on the human body should be possible].
PMID- 9640934
TI - [Fluid can be administered via a tube in acute diarrhea in children].
PMID- 9640935
TI - [A new therapeutic program in advanced ovarian cancer. Good results with
decentralized cytostatic therapy].
AB - A trial of decentralised cytostatic (carboplatin + cyclophosphamide) treatment of
advanced ovarian cancer under centralised supervision, carried out in the
southern health care region, yielded good results. As carboplatin and
cyclophosphamide cause myelosuppression which is commonly most manifest two weeks
after treatment, increasing dosage intervals and reducing dosages is often
necessary. However, compliance with the protocol for increasing dosage intervals
and reducing dosages was found to be equally good at Lund and at the various
local clinics. Although no significant difference in survival was found between
patients treated with carboplatin and cyclophosphamide according to this model
and patients treated with cisplatin combined with doxorubicin or epirubicin (P =
0.42), the former protocol is more appropriate for use in the out-patient clinic.
PMID- 9640936
TI - [Specimen culture from all children in a day care center because of an outbreak
of streptococcal infection].
AB - In an outbreak of recurrent group A streptococcal (GAS) pharyngotonsillitis
between January and February 1997 at a Swedish preschool, involving 58% (11/19)
of the children and several family members, clinical examination showed few of
the children to manifest signs and symptoms of tonsillitis. However, throat
specimens yielded GAS growth of the same T-type in 42% (8/19) of the children and
in 30% (6/20) of family members, but in none of the staff. Strict hygiene,
appropriate antibiotic treatment of all culture-positive individuals irrespective
of symptoms, and non-attendance at the preschool during the first two days of
treatment promptly terminated the outbreak and there were no cases of recurrence.
PMID- 9640937
TI - [Genetic factors are often found inl Alzheimer disease. An extensive twin study
to clarify the heredity-environment relationship].
AB - Genetic and environmental risk factors are central concerns in dementia research.
Through twin studies one can study the relative importance of genetic and
environmental risk factors. One such study, based on the Swedish Twin Registry,
shows that genetic effects are of considerable importance for developing
Alzheimer's disease, even late in life, but that environmental factors are also
important. For vascular dementia, the results indicate that non-genetic factors
are of primary importance.
PMID- 9640938
TI - [Too many cases of recurrences after inguinal hernia surgery. New surgical
methods and better follow-up should remove the shortages].
PMID- 9640939
TI - [Successively improved prognosis in erythrocyte immunization].
AB - Prognosis in cases of erythrocyte immunisation has improved continuously over the
past decades. Morbidity and mortality have been reduced by improvements in
management, including screening programmes, non-invasive ultrasound evaluation
and invasive procedures. The article provides an outline of the latest
developments in the management of erythrocyte immunisation, and several
controversial issues are discussed, such as antibody screening, strategies for
the reduction of antibody titres, and the organisation of care.
PMID- 9640940
TI - [Oral health among immigrants. An increasing need for dental care. Children are a
high risk group for caries].
PMID- 9640941
TI - [General practitioners prescribe more and more antidepressive agents. Repeated
studies of prescriptions in a small municipality].
PMID- 9640942
TI - [A new therapeutic model in autism. Interdisciplinary habilitation in specialized
units].
PMID- 9640943
TI - [Is it the end of scientific truth?].
PMID- 9640944
TI - Liability to and for employees while attending seminars.
PMID- 9640945
TI - Preventing claims in outpatient care environments.
PMID- 9640946
TI - Physician community involvement. Working within your area to promote better
health.
AB - How many times have you been asked to participate in a meeting, forum, or task
force to address a community health issue in the last few years? Opportunities
seem to crop up almost weekly as non-profit organizations acclimate to meet
changing needs and health systems continue to adapt to market forces. But
participating in ongoing community projects, or even attending periodic meetings,
draws time away from practice and professional obligations and limits an already
modest supply of personal time. Is involvement in a community collaborative
effort worth the time? And, if so, what are the benefits and challenges to
physicians, health systems, and communities from this type of investment?
PMID- 9640947
TI - New classes for office staff. MSMS Educational Program focuses on improving your
practice.
AB - Have you ever wondered how your practice could benefit from a highly trained and
specialized office staff? It could improve how patients are treated and enhance
the day-to-day tasks required to run an office. Medical office personnel are
essential, and their continued education can directly affect the operation and
perception of your practice.
PMID- 9640948
TI - How could alternative therapies affect your practice?
PMID- 9640949
TI - "Gearing up" for summer. Quick tips and biking essentials.
AB - With any luck, at about the time this appears in print I'll be appearing on the
street in my favorite part of my fitness program: bicycling. I don't claim to be
an expert--my family thinks I'm Miguel Indurain because I can ride 20 miles at a
time, and I think I'm Marco Pantani because I'm short, bald, and good on hills-
but I've learned a fair amount in my last three years of riding. If you're an
experienced rider you probably know at least as much as I do, but if you're a
beginner--or beginning over after a long hiatus, as I did--then I have some
suggestions for you.
PMID- 9640950
TI - Marshall Brown, MD. Bringing care to Guatemala.
AB - Medical equipment that is obsolete to a physician in the United States may be
considered "a thing of beauty" to a counterpart in a Third World country. So
declares Marshall Brown, MD, and otolaryngologist from Saginaw. Retired--in
theory--since 1994, he has devoted much of his time to gathering donations of
unused and outdated medical equipment for a hospital near Guatemala City,
Guatemala. In addition, he has seen that the donated supplies are refurbished and
get to where they're needed--sometimes flying the supplies there himself.
PMID- 9640951
TI - Batten down the hatches.
PMID- 9640952
TI - Urban medicine: beyond the stereotype.
PMID- 9640953
TI - Successful hospitalist program in Duluth.
PMID- 9640954
TI - The case for physician practice management companies. And why they haven't taken
hold in Minnesota.
PMID- 9640955
TI - Minnesota's new Rural Health School.
PMID- 9640956
TI - Administrative simplification rules released.
PMID- 9640957
TI - Managed care in rural Minnesota. Family physicians' attitudes and perceptions.
AB - Prepaid managed care medicine has become dominant in urban Minnesota and is
making its way into the rural setting. This study assesses the attitudes of rural
family practice physicians in Minnesota toward managed care. A survey, consisting
primarily of five-point Likert scale statements, was mailed to 798 rural
Minnesota family practice physicians, with a response rate of 35% (281
respondents). We tabulated overall responses and made comparisons based on
practice characteristics and years in practice. Twenty physicians participated in
a follow-up telephone interview. We also conducted telephone interviews with 10
representatives from managed care organizations. Both positive and negative
attitudes toward managed care emerged. Two-thirds of respondents did not feel
that their time with patients was diminished under managed care. However, 67% of
respondents felt that managed care organizations had failed to incorporate rural
patients' specific needs into their policies. Only 7% of respondents felt that
managed care organizations adequately explained their benefits packages to
enrollees. Rural family practitioners' apparent disillusionment with current
managed care models merits the attention of those concerned with medical care in
rural areas.
PMID- 9640958
TI - Compliance ... or else!
PMID- 9640959
TI - Fraud investigations: the heat is on.
PMID- 9640960
TI - Angiotensin-converting enzyme inhibitor cilazapril suppresses expression of basic
fibroblast growth factor messenger ribonucleic acid and protein in endothelial
and intimal smooth muscle cells in a vascular injury model of spontaneous
hypertensive rats.
AB - The relationship between the expression of basic fibroblast growth factor (bFGF)
messenger ribonucleic acid (mRNA) and protein, a potent mitogen for vascular
smooth muscle cells in vivo, and administration of the angiotensin-converting
enzyme inhibitor cilazapril, which suppresses smooth muscle cells proliferation
in denuded arteries, was studied in spontaneously hypertensive rats using the in
situ hybridization technique and immunohistochemical study. The effect of
cilazapril on neointimal formation through modification of bFGF expression was
evaluated using the increased tissue expression of the renin-angiotensin system
in spontaneously hypertensive rats. Arterial injury was produced by using balloon
catheter denudation in the left carotid artery of rats. The effects were
evaluated 2 weeks later. bFGF mRNA and protein were observed only in the
endothelial cells of sham-operated rats. bFGF mRNA and protein were observed in
both endothelial cells and intimal smooth muscle cells in operated rats receiving
only vehicle. Expression of bFGF mRNA and protein was suppressed in both
endothelial cells and intimal smooth muscle cells of operated rats receiving
cilazapril. These data suggest that cilazapril suppresses smooth muscle cell
proliferation through modification of the expression of bFGF mRNA and bFGF
protein in addition to other genes.
PMID- 9640961
TI - Microsurgical treatment of intramedullary spinal cord tumors.
AB - Eighty patients with intramedullary spinal cord tumors were treated by
microsurgical methods between 1988 and 1996. Twenty-nine patients were diagnosed
with astrocytoma, 36 with ependymoma, five with metastasis, four with lipoma,
three with dermoid or epidermoid tumor, two with neurofibroma, and one with
neuroma. Vascular and infectious lesions (such as abscesses and
hemangioblastomas) were excluded. After laminectomy, total removal of the lesion
was achieved in 68 of 80 patients and subtotal removal in 12. Postoperative
radiation therapy was performed in 13 of 80 patients. The follow-up period ranged
from 12 to 92 months (mean 42.2 months). All patients underwent preoperative and
postoperative magnetic resonance imaging at intervals ranging from 3 months to 5
years postoperatively. Four patients showed clinical and radiological evidence of
local tumor recurrence during the follow-up period. Four patients died 5 months
to 15 months postoperatively from the re-expansion of their primary metastatic
disease. The operative results at long term (after the 6th postoperative month)
were better than the results at short term (before the 6th postoperative month)
and revealed clinical improvement in 63, no change in 10, and deterioration in
seven patients. We recommend early radical surgery, whenever possible, to be
performed when the patient's neurological status is still good. Subtotal removal
and irradiation are better for malignant or metastatic tumors. Partial
decompressive removal is best for large intramedullary lipomas. Plastic
laminotomy with preservation of the intervertebral joints is especially
recommended in young or middle-aged patients.
PMID- 9640962
TI - Extensive edema in the thalamus caused by thrombosed basilar artery aneurysm.
AB - A 69-year-old female presented with sudden onset of truncal ataxia, urinary
incontinence, mental confusion, and Parinaud's sign. With conservative treatment,
her ataxia and urinary incontinence resolved. Magnetic resonance (MR) imaging
disclosed a round mass with laminated intramural hemorrhage in the third
ventricle. Right vertebral angiography demonstrated a giant aneurysm in the
distal basilar artery. Xenon-enhanced computed tomography showed that cerebral
blood flow (CBF) was reduced in the thalamus bilaterally and was paradoxically
decreased by acetazolamide. Two months later, MR imaging showed that the
intramural hemorrhage had shrunk, and the edema in the thalamus was resolving.
The CBF reduction and vascular response to acetazolamide had reversed to some
extent. A partially thrombosed giant aneurysm can grow acutely as the result of
fresh intramural hemorrhage. The edema is secondary to ischemia and loss of
vasoresponsivity.
PMID- 9640963
TI - Central neurocytoma presenting with intratumoral hemorrhage 15 years after
initial treatment by partial removal and irradiation.
AB - A 50-year-old male presented with a central neurocytoma with intratumoral
homorrhage. He had undergone partial removal of the tumor and postoperative
radiation therapy 15 years previously. He was followed as an outpatient after the
initial treatment, and there was no evidence of regrowth of the residual tumor.
Removal of the hematoma and biopsy of the tumor were performed. Abnormally
developed blood capillaries in the tumor may have undergone disturbances of
circulation caused by irradiation which resulted in bleeding. Patients with
partially resected central neurocytomas which have low proliferative potential
may not require radiation therapy, due to the benign nature and the risk of
delayed complications of irradiation including intratumoral hemorrhage.
PMID- 9640964
TI - Pilocytic astrocytoma of the velum interpositum.
AB - A 72-year-old male presented with a pilocytic astrocytoma in the velum
interpositum manifesting as a 5-day history of dizziness attacks and unstable
gait. Computed tomography and T1-weighted magnetic resonance imaging with
gadolinium enhancement demonstrated a small, homogeneously enhanced mass in the
velum interpositum. The tumor was removed subtotally, and the structure of the
splenium was intact. The histological diagnosis was pilocytic astrocytoma. The
MIB-1 growth fraction was 5%. The tumor may have originated from the splenium or
the thalamus. The aggressive histology indicates the need for close neuroimaging
follow-up.
PMID- 9640965
TI - Glioblastoma following radiotherapy in a patient with tuberous sclerosis.
AB - A 26-year-old male with tuberous sclerosis developed a glioblastoma in the right
temporal lobe 8 years after surgical excision and irradiation of a subependymal
giant cell astrocytoma. The glioblastoma was probably an irradiation-induced
tumor. Irradiation should not be given routinely for subependymal giant cell
astrocytoma.
PMID- 9640966
TI - Plasma cell granuloma extending from the extracranial to the intracranial space
associated with Epstein-Barr virus infection.
AB - A 70-year-old male presented with a plasma cell granuloma extending from the
extracranial to the intracranial space. Findings of preoperative magnetic
resonance imaging and intraoperative observation indicated that the lesion
extended from the temporal muscle to the subarachnoid space, penetrating the
frontal bone. The subarachnoid lesion was composed of neutrophils indicating the
presence of acute or subacute inflammation. The final diagnosis of the resected
tumor was plasma cell granuloma. High levels of antibodies against Epstein-Barr
(EB) virus in the cerebrospinal fluid and the immunohistochemical demonstration
of EB nuclear antigens in the plasma cell granuloma suggested that EB virus
infection was associated with the development of plasma cell granuloma in this
patient.
PMID- 9640967
TI - Pineal dermoid cyst developing 18 years after gross total removal of a pineal
mature teratoma.
AB - A 21-year-old male presented with a pineal dermoid cyst manifesting as headache
and diplopia. He had undergone gross total removal of a pineal mature teratoma 18
years before and had done well until recently. Diffusion-weighted magnetic
resonance imaging showed a region of high signal intensity due to a round mass in
the pineal region and extending into the trigone of the right lateral ventricle.
Subtotal excision of the tumor was achieved. Histological examination showed an
epidermoid cyst consisting of keratinized stratified squamous epithelium and
connective tissue. Intraoperative observation had detected black hairs, so the
diagnosis was dermoid cyst. The dermoid cyst may have arisen from a microscopic
remnant of the cyst wall of the original pineal mature teratoma. The regrowth of
a dermoid cyst 18 years after gross total removal of a mature cystic teratoma in
the pineal region is exceptional. However, careful follow-up of patients who
undergo gross total removal of a pineal teratoma is recommended for a period more
than that of the patient's age at surgery plus 9 months.
PMID- 9640968
TI - Theodor Kocher, Hayazo Ito, and Harvey Cushing in Berne, Switzerland.
PMID- 9640969
TI - ECL cells involvement in the isoproterenol-induced gastroprotection. An
ultrastructural study.
AB - The central and peripheral adrenergic systems are involved in the regulation of
several functions in the gut including the maintenance of gastric
microcirculation and gastric secretion but little is known about the role of the
adrenergic system, in particular, beta-adrenoceptors in the phenomenon of
gastroprotection. In this study acute gastric lesions were provoked by an
intragastric (i.g.) application of 100% ethanol in rats with topical application
of isoproterenol (ISO) (1 mg/kg) or subcutaneous (s.c.) administration of
ranitidine (RAN) (40 mg/kg) or both. An area of gastric lesions was determined by
planimetry, gastric blood flow (GBF) was determined by H2-gas clearance technique
and gastric specimens were taken for histology and electron microscopy. It was
found that ISO reduced ethanol-induced gastric mucosal lesions and this effect
was accompanied by a rise in GBF. In contrast, RAN applied s.c. in a dose that
produced almost complete achlorhydria, failed to affect ethanol-lesions but
attenuated significantly ISO induced gastroprotection and abolished the increase
in the GBF induced by this beta-adrenoceptor agonist. Histology and
ultrastructural study revealed that pretreatment with ISO influenced HCl
production reflected by the elaborated secretory surface of parietal cell
intracellular canaliculi. All these changes were accompanied by the
ultrastructural changes in Golgi apparatus in ECL-like cells (histamine storing
cells). Pretreatment with ISO caused the collapse of Golgi profiles and only
peripheral sacs were not compressed but such a change was not observed after RAN
treatment. The best developed Golgi was, however, seen in the control rats
without any treatment. Secretory granules in ECL cells were significantly
expanded after pretreatment with ISO but did not show significant morphological
changes in rats pretreated with RAN. We conclude that 1. ISO protects the gastric
mucosa injured by ethanol presumably due to increased gastric microcirculation,
and 2. ECL-like cells are actively involved in ISO-induced gastroprotection
possibly by the increased histamine release which is reflected by ECL-cell and
Golgi apparatus morphology.
PMID- 9640970
TI - Immunohistochemical status of p53, mdm2 and Ki-67 in malignant fibrous
histiocytoma.
AB - The aim of the study was to evaluate the frequency of p53, mdm2 and Ki-67
immunopositivity in MFH, and to investigate possible associations of their
expression with the grade of malignancy and predominant histological pattern-
storiform, pleomorphic and myxoid subtype of MFH. A total number of 51 tumor
samples from 21 primary and 30 secondary MFHs was studied using monoclonal anti
p53 (DO-78, DAKO), anti-mdm2 (1F2, NOVOCASTRA) and polyclonal anti-Ki-67 (DAKO)
antibodies. The p53 immunopositivity was observed in 32.7% of all tumor samples
(in 36.8% of primary and in 30% of recurrent and metastatic tumors). The mdm2
immunopositivity was noted in 34.8% of all tumor samples (in 33.3% of primary and
35.7% of secondary tumors). The mean percentage of p53, mdm2 and Ki-67 positive
cells was 15.5, 8.8 and 7.05, respectively. The mean Ki-67 LI was statistically
higher in grade 3 than in grade 2 of malignancy (p = 0.006). A significant
correlation was found between mdm2 positivity and histological subtypes of MFH-
storiform and pleomorphic types were more frequently mdm2 positive than myxoid
variant (p = 0.035 and p = 0.009, respectively). No such correlation was observed
for p53 positivity of tumors and subtypes, but there was a statistically
significant difference in the percentage of p53 positive cells between storiform
and myxoid type (p = 0.049). We also noted more tumors expressing high percentage
(over 20%) of mdm2 positive cells in pleomorphic and storiform subtypes than in
myxoid variant (p = 0.048). The Ki-67 LI was also higher in pleomorphic than in
other types of MFH (p = 0.012). A strong positive correlation was found between
p53 positivity and mdm2 positivity of tumors in primary MFHs (p = 0.00146). p53
and mdm2 positive tumors were mainly in grade 3 of malignancy, but no
statistically significant correlations were noted. A positive correlation between
the percentage of p53 positive cells and Ki-67 positive cells (p = 0.0028) was
observed.
PMID- 9640971
TI - Glomerular basement membrane thickness in minimal change disease. The
ultrastructural quantitative study.
AB - Fifteen renal biopsy specimens from adult patients with minimal change disease
(MCD) for whom both light and electron microscopy as well as immunofluorescence
microscopy and full clinical data were available were examined quantitatively and
compared with six normal controls. The electron micrographs of the glomeruli were
scanned in Primax flatbed A4 scanner and then morphometric investigations were
performed by means of a computer image analysis system to compare glomerular
basement membrane (GBM) thickness and to study whether this parameter could
correlate with the degree of proteinuria. The study revealed that the mean GBM
thickness was lower in MCD patients as compared with normal controls (299.2 nm
versus 338.8 nm), but this difference did not reach statistical significance.
Interestingly, the present investigations showed that the GBM thickness tended to
be related directly to proteinuria and not inversely as it might be expected, but
this relationship was not significant, either. In conclusion, we can confirm the
tendency to GBM thinning in adult MCD patients. It should be also noted, that GBM
thinning did not increase the degree of proteinuria in these cases.
PMID- 9640972
TI - Tracheobronchial amyloidosis.
AB - The authors have described eleven cases of tracheobronchial amyloidosis, in 6 men
and 5 women with a mean age of 58.7 years. The follow-up period ranged from
several month to six years. The clinical picture and histopathological changes in
bronchoscopic and postmortem sections in two patients were described. In all
cases immunohistochemical examinations for the presence of amyloid AA, AL,
transthyretin (prealbumin) and beta 2-microglobulin were performed. In six cases
the presence of transthyretin was found. The remaining reactions were negative.
Resorptive giant cells reaction to amyloid was observed in 3 transthyretin
positive cases and 1 transthyretin negative case. Four cases with negative
amyloid in the examination for the presence of transthyretin accompanied
bronchial carcinoma, all these cases were men with a mean age of 63.0 years.
PMID- 9640973
TI - NSAIDs associated nephropathy.
AB - Renal biopsy of 32 patients who developed renal complications after treatment
with nonsteroidal anti-inflammatory drugs (NSAIDs) were studied. The treatment
with NSAIDs in these cases was used for many reasons such as: headaches,
toothaches, dysmenorrea, osteochondrosis, polyarthritis and acute respiratory
infections. The renal function of these patients, before the treatment with
NSAIDs was normal. The renal biopsies were studied by light, electron and
immunofluorescence microscopy. In 32 cases treated with NSAIDs renal changes were
shown. There types of morphological changes were found: focal glomerulonephritis
with crescents (FGN)(5 cases), acute tubulo-interstitial diseases (ATID)(8 cases)
and lipoid nephrosis with tubulo-interstitial nephritis (LN)(19 cases). FGN and
ATID possibly represent a hypersensitive reaction of predominantly humoral (FGN)
or cellular (ATID) mechanisms. These types of reaction are also seen to occur
with the use of various drugs (most commonly with penicillin type antibiotics).
LN on the other hand is rarely, if ever, seen with any drugs but NSAIDs and
therefore seems to be a characteristic change for NSAIDs and possibly related to
the inhibition of renal prostaglandin synthesis by NSAIDs. NSAIDs-associated
renal dysfunction is mainly observed in patients of an increased use of NSAIDs
with ineffective circulatory plasma volume (advanced age, cardiovascular disease,
overweight and hypovolemia of various causes).
PMID- 9640974
TI - A cytotelepathology consulting station.
PMID- 9640975
TI - Primary intrapericardial malignant fibrous histiocytoma. A case report.
AB - A case of giant intrapericardial malignant fibrous histiocytoma has been
reported. A brief review of primary cardiac tumours has been presented taking
into account differential diagnosis of neoplasms of histologically myxomatous
nature.
PMID- 9640976
TI - [Fc gamma receptors in human placenta].
AB - This review summarizes the status of our knowledge on the structure, expression
and function of Fc gamma R in the placenta. The discovery in syncytiotrophoblast
of an MHC class I--related FcR, of the type responsible for intestinal uptake of
milk IgG in suckling rats and mice is also described.
PMID- 9640977
TI - [Soluble IL-6 receptors].
AB - Both subunits of IL-6 membrane--associated receptor, IL-6R and gp130 can exhibit
in a soluble forms--sIL-6R and sgp130 respectively. Soluble IL-6 receptor (sIL
6R) can bind IL-6 and mediate IL-6 function through association with gp130 which
is the signal transducing protein. In contrast to other receptors, sIL-6R has a
potential to enhance the IL-6 biological function. sIL-6R and sgp130 were found
in appreciable amounts in body fluids, although the exact cellular source and
function of these proteins are not completely clear.
PMID- 9640978
TI - [TNF-alpha preactivation (priming) of neutrophils--effect on selected neutrophil
functions].
AB - Human polymorphonuclear cells (neutrophils) are fundamentally protective, but
extracellular release of proteolytic enzymes and oxygen radicals may lead to
tissue destruction. Granulocyte function can be rapidly amplified by
environmental factors through a mechanism termed "priming". Priming enhances the
neutrophils' ability to respond to a secondary agonist, with increased adhesion,
respiratory burst, and degranulation. This review summarizes the effects of TNF
alpha priming on the neutrophils' function.
PMID- 9640979
TI - [Controlled release antigen from the injection site--new model for a single-shot
vaccination?].
AB - Continuously increasing number of available vaccines and a wide use of mass
vaccination campaigns lead to the development of simpler methods of vaccine
delivery. There is the WHO-sponsored project, including several scientific
groups, which aims to reduce the number of repeated administrations of vaccines
required for long-term protection and to obviate the need for booster
immunization. Such a task may be achieved by the use of controlled-release
parenteral systems. One such delivery system comprises microspheres constructed
from biodegradable, biocompatible polymers based on poly lactic/glycolic acid.
Recent developments of a single-shot tetanus toxoid, encapsulated in the
biodegradable polymeric microspheres or microcapsules are reviewed. There are
promising advances in the WHO-sponsored project. However, further efforts are
needed to elaborate an affective late release of antigen and to obtain a strong
booster effect in vaccinated animals.
PMID- 9640980
TI - [Wound repair].
PMID- 9640981
TI - [Metabolites of arachidonic acid (eicosanoids) in the airways--the role of
epithelium in synthesis of eicosanoids].
AB - Arachidonic acid metabolites are potent modulators in physiology and mediators in
pathophysiology of airways. They play important role in allergic diseases. There
are two main sources of eicosanoids found in nasal and bronchial lavages: airway
epithelial cells and influx cells. Authors described spectra of eicosanoids
produced by epithelial cells in vitro and compare them with in vivo findings. The
review of similarities and differences between arachidonic acid metabolism in
human upper and lower airways is also included.
PMID- 9640982
TI - [Body dysmorphic disorder: clinical picture, diagnostic criteria, prevalence,
course and treatment].
AB - The article presents historical conceptions of dysmorphphobia and a review of
recent references concerning aetiology, criteria for diagnosis of this disorder
in new classifications of mental disorders (DSM-IV and ICD-10), course, and
proposition of treatment. The author described characteristic personality traits
of patients with dysmorphophobia and mental disorders, which are very often
comorbid with this disorder (obsessive-compulsive disorder, phobia, delusional
disorder-somatic type) and mental disorders in first-degree relatives of persons
with dysmorphophobia.
PMID- 9640983
TI - [Results of long-term observation (3-11 years) of patients with dual diagnosis:
body dysmorphic disorder and delusional disorder, somatic type].
AB - This work presents results of a retrospective and prospective research of 15
persons with a double diagnosis: body dysmorphic disorder, and delusional
disorder, somatic type. It was established that these disorders starting in
adolescence, occurred in persons who earlier had traits of avoidant and obsessive
compulsive personality or social phobia. In most subjects with dysmorphophobia
there was comorbidity of dysthymia or major depression. An improvement in the
state of these patients, most often after implementation of complex therapeutic
measures: psychotherapy as well as pharmacotherapy with neuroleptic and SSRI's or
clomipramine has to do with withdrawal of delusions, whereas the symptoms of body
dysmorphic disorder usually last for years. In some patients delusional disorders
had a tendency to reoccur or to be chronic, and lead to a considerable impairment
of social functioning.
PMID- 9640984
TI - [Liaison between body dysmorphic disorder and eating disorders].
AB - This study presents the cases of anorexia nervosa which began with a body
dysmorphic disorder lasting for at least 6 months. In some subjects (25%) there
was comorbidity of 3 mental disorders: anancastic personality or obsessive
compulsive disorder + dysmorphophobia + anorexia nervosa or dysmorphophobia +
anorexia nervosa + depressive disorder (dysthymia or major depression). The
author considers the conception that in some cases dysmorphophobia and anorexia
nervosa are a spectre of obsessive-compulsive disorder or affective disorders in
adolescents.
PMID- 9640985
TI - [Multifactorial aspects of eating disorders].
AB - A group of patients (52 women and 3 men) aged 12-39 with the diagnosis of
anorexia nervosa (51 persons) and bulimia nervosa (4 persons) treated in the I
Psychiatry Department of Medical University of Gdansk between 1972-1994 was
studied. The diagnostic criteria were in accord with the DSM-IV. Among anorectic
patients 45 persons were of restricting type and 6 were of bulimic type. Duration
of illness was 1-14 years. Most of the patients were still students. Analysis of
the aspects of eating disorders showed family conflict situations, single
parents, conflicts between parents, competition at home. The patients presented
fearful attitude, egocentrism, problems with acceptation of the gender role,
obsessive-compulsive traits. In 36.7% cases minimal brain damage symptoms were
found. Statistically significant weight gain was observed after neuroleptic
treatment.
PMID- 9640986
TI - [The influence of early childhood experiences on depression among medical
students. Preliminary study].
AB - The aim of this study was an attempt to estimate depression prevalence in medical
students. Simultaneously we tried to asses the impact of early negative
experiences on the level of depression in that population. We examined 92 third
year medical students of the Silesian Academy of Medicine (54 women and 38 men)
at the age from 20 to 24. Frequency and intensification of depression were
assessed by using Beck Depression Inventory. Early experiences including negative
and positive ones were estimated with the use of a self prepared repertory test
called "biographical path", based on Personal Construct Theory of George Kelly.
The obtained results indicated that 25% of examined students had depression
symptoms. These students were exposed more frequently to early negative
experiences than students without depression. In childhood depressive students
were under pressure of their environment to score successes. If they did not
realise these expectations they were exposed to discontent and frustration of
their parents. Depressive students came less frequently into contact with other
people and acquired independence later than non depressive students.
PMID- 9640987
TI - [Memory processes in endogenous depression].
AB - The thesis aims to answer the questions about the profile of mental ability in
endogenous depression and to decide whether self-estimation of depressive
symptoms influences the results achieved by patients in memory tests. Fifty six
patients suffering from endogenous depression have been examined. The following
methods have been applied: Mini Mental State Examination, Benton Visual Retention
Test, Beck Depression Inventory, hold tests: Vocabulary, Information,
Comprehension and Digit Span of Wechsler Adult Intelligence Scale (WAIS), Rey
Osterrieth Complex Figure, Auditory Verbal Learning Test, DCS Weidlich. General
status of cognitive functions correlates with the profile of specific kinds of
memory results, particularly with delayed memory. Self-estimation of depressive
symptoms intensity is mostly influenced by memory capacity, visuomotorial factor,
functions of perception and lingual factor. High correlation between verbal and
non verbal learning shows uniform influence of depression on the process of
learning.
PMID- 9640988
TI - [Depression in epileptic patients with and without history of suicidal attempts:
preliminary report].
AB - Depression is a significant problem in epilepsy. Suicides occur in epileptic
patients five times more often than in general population. Material included 34
epileptics with 76 suicidal attempts and 24 patients with no history of suicide.
Psychical state was studied with Beck Depression Inventory and Hamilton
Depression Rating Scale. In the group with suicidal attempts 65% of patients had
depression (54.5% of them had major depression) and in group without suicide
attempts depression was noted in 54% (23% with major depression). Patients with
depression were divided into two groups: group I with suicidal attempts and group
II without history of suicide. In group I more patients were alcohol abusers (50%
vs 31%), more were treated because of epilepsy longer than 10 years (59% vs 46%)
and more had tonic-clonic seizures (82% vs 46%). In group I, 54% of patients were
on polytherapy (more than half of them with fenobarbital). In group II, 31% of
epileptics were on polytherapy (no one with fenobarbital). Major depression was
significantly more frequent in epileptics with suicidal attempts. The severity of
depression may influence the risk of suicide. Major depression may be associated
with late age of onset of epilepsy, longer treatment duration, tonic-clonic
seizures, polytherapy (mainly with fenobarbital) and alcohol abuse.
PMID- 9640989
TI - [Carl Wernicke's school of neuropsychiatry in Wroclaw].
PMID- 9640990
TI - [Alois Alzheimer's traces in Wroclaw].
PMID- 9640991
TI - Summary of a National Institute of Mental Health workshop on late-life anxiety.
PMID- 9640992
TI - The acute and chronic performance effects of alprazolam and lorazepam in the
elderly: relationship to duration of treatment and self-rated sedation.
AB - We examined the acute performance and sedative effects of single high and low
doses of alprazolam and lorazepam, both before and after chronic, 3-week b.i.d.
treatment in elderly adults. The effects of chronic treatment also were examined
in this parallel, double-blind, placebo-controlled study. Initial acute low doses
significantly impaired total recall and increased intrusion errors. High doses
also impaired delayed recall and critical flicker fusion threshold (CFF). Only
chronic treatment with high-dose alprazolam increased intrusions and self-rated
sedation. Single-dose rechallenge after chronic treatment was associated with
significantly less impairment than the initial challenge in memory tasks but not
in the discriminant reaction time (DRAT) task. For most memory measures, the
development of tolerance was only partial; rechallenge still produced significant
deficits in relation to placebo. The development of tolerance was task-specific
and depended on drug type and dosage. Despite impairments in various memory
functions, CFF, and DRAT, volunteers did not report significant drug-induced
changes in sedation.
PMID- 9640993
TI - Assessment issues in treatment research of pediatric anxiety disorders: what is
working, what is not working, what is missing, and what needs improvement.
AB - Reviewing the strengths and weaknesses of the rating scales for anxiety disorders
makes it possible to select appropriate measures for use in a multisite treatment
study of children and adolescents with DSM-IV-diagnosed anxiety disorders.
Categorical diagnosis for study inclusion is provided by the K-SADS-PL, which has
strong published psychometrics for anxiety disorders. Broadband symptom ratings
of diverse pediatric psychiatric disorder can be obtained at baseline by the
parent-scored Child Behavior Checklist. Anxiety symptom monitoring may be
provided by the use of two psychometrically strong self-report measures, the MASC
and the SCARED. Weekly global ratings are provided by the CGI whose scale points
have been enhanced by detailed anchors; in addition, the raters all trained on
practice vignettes to calibrate their scoring. Clinician-based ratings of the
patient's anxiety symptoms can be carried out in adolescent patients using the
HAM-A. The newly developed Children's Anxiety Rating Scale promises to cover the
full pediatric age range as a clinician-based anxiety rating instrument, but must
first be subjected to formal psychometric and treatment sensitivity evaluation.
PMID- 9640994
TI - Changes on the Temperament and Character Inventory after paroxetine treatment in
volunteers with generalized anxiety disorder.
AB - Previously untreated symptomatic volunteers with generalized anxiety disorder
(GAD) performed the Temperament and Character Inventory at baseline and after 4
to 6 months of paroxetine treatment. Scores from 29 volunteers were analyzed with
paired t-tests. A marked reduction was noted in Harm Avoidance and a marked
increase was noted in Self-Directedness. Smaller changes were noted in
Cooperativeness and Novelty Seeking. Overall, treatment was associated with a
reduction in maladaptive personality traits.
PMID- 9640995
TI - The efficacy of new pharmacological treatments for panic disorder: evaluating the
trials.
PMID- 9640996
TI - Pivotal studies of clonazepam in panic disorder.
AB - Clonazepam has recently been approved for the treatment of panic disorder. Two
large placebo-controlled efficacy trials were completed; superior benefit was
found for the drug on most measures. The studies are reviewed in relation to the
criteria set forth by Shear and Maser with respect to design, diagnostic, and
outcome measures. Most, but not all, recommended measures were used. Measurement
of panic attack severity, duration, and frequency were generally the least
satisfactory of all outcome variables and failed to provide the consistent
benefit that was found with other measures. A slow discontinuation phase was
employed, and a benign withdrawal course was noted, although withdrawal from
higher doses was associated with more emergent symptomatology.
PMID- 9640997
TI - Efficacy studies of paroxetine in panic disorder.
AB - The optimal assessment of treatment outcome for studies assessing the efficacy of
treatments for panic disorder has been a controversial topic. A recent National
Institute of Mental Health (NIMH)-sponsored consensus conference addressed this
important topic, and a summary paper regarding assessment of essential elements
of the disorder resulted. Among other conclusions, it was agreed that several
different domains should be considered as essential. This article reviews three
pivotal studies assessing the efficacy of paroxetine for the treatment of panic
disorder, and evaluates these studies for inclusion of those variables considered
essential. Additionally, some data were reanalyzed to determine the percentage of
individuals in these studies who are unequivocal responders (i.e., were both
panic-free and rated on global assessment as responders). A longer-term treatment
and relapse study is also mentioned briefly.
PMID- 9640998
TI - Methodologies and outcomes from the sertraline multicenter flexible-dose trials.
AB - This article summarizes the results of a combined analysis from two identical
multicenter clinical trials that investigated the efficacy and safety of
sertraline versus placebo for treating panic disorder. Patients with panic
disorder who were treated with sertraline had a statistically significant
reduction in the mean number of panic attacks per week (the primary efficacy
measure) as compared with placebo (4.8 vs. 2.5, p < .001). Sertraline-treated
patients also showed greater improvement that was statistically significant on
several ratings of panic disorder symptomatology and functioning. The design
characteristics, clinical rating measures, and outcome measures in these trials
included most of the features deemed essential by Shear and Maser (1994) in their
summary of the NIMH Consensus Conference for the development of standardized
assessments for panic disorder. This suggests that the NIMH Consensus Conference
played a key role in developing successful multicenter pharmacological treatment
studies, such as this one that ultimately demonstrated that sertraline was an
effective treatment for panic disorder.
PMID- 9640999
TI - Efficacy studies of alprazolam in panic disorder.
AB - Alprazolam was the first pharmacological agent to be approved for the treatment
of panic disorder. In seeking that approval, the Upjohn Company conducted the
earliest large, multicenter drug trials in panic disorder, involving nearly 1,700
patients in 14 countries. The administrative and quality assurance procedures
developed for those studies have become a model for subsequent research. Despite
this history, the efficacy of alprazolam for panic disorder has been contested.
This article summarizes the published multicenter data from the perspective of
the assessment criteria recommended by Shear and Maser (1994) and presents
comparative findings from the Philadelphia maintenance study and the
London/Toronto study of alprazolam and exposure therapy. Data on relapse
following treatment discontinuation are also reviewed.
PMID- 9641000
TI - Commentary: the treatment of panic.
PMID- 9641001
TI - Long-term experience with clonazepam in patients with a primary diagnosis of
panic disorder.
AB - This study examined the use patterns and efficacy of the high potency
benzodiazepine (HPB) clonazepam in panic patients who were treated and followed
naturalistically in the Massachusetts General Hospital Longitudinal Study of
Panic Disorder. Of 204 patients followed over a 2-year period, 46 percent were
receiving clonazepam alone or in combination with an antidepressant. Treatment
was not controlled at initial evaluation or during the followup period. The main
variables assessed in this analysis included global severity of the panic
disorder and stability of clonazepam dose. All treatment groups tended to improve
over time without significant differences in outcome between groups. Clonazepam
doses remained stable over time. Results of this study suggest that treatment of
panic disorder with the HPB clonazepam achieved and maintained a therapeutic
benefit similar to that obtained with alternative pharmacologic treatments,
without the development of tolerance as manifested by dose escalation or
worsening of clinical status.
PMID- 9641002
TI - Low-dose venlafaxine treatment in panic disorder.
AB - Venlafaxine, a structurally novel antidepressant that combines mechanisms of
action of both the cyclic antidepressants and SSRIs, may be effective in the
treatment of panic disorder. Thirteen patients with DSM-IV panic disorder with or
without agoraphobia participated in an open-label, fixed-flexible dose treatment
study with venlafaxine. All patients who completed the 10-week trial exhibited
statistically significant decreases in scores on anxiety symptoms as well as
complete cessation of panic attacks at an effective mean daily dose of 47 mg per
day. Venlafaxine was well tolerated in all completers. Venlafaxine may be an
effective antipanic agent, even at lower than typical antidepressant dosages.
PMID- 9641003
TI - Effect of venlafaxine on the pharmacokinetics of alprazolam.
AB - Potential pharmacokinetic effects of venlafaxine on alprazolam, a substrate of
the cytochrome pigment 450 (CYP) isoenzyme CYP3A4, were investigated in 16
healthy volunteers. A single 2-mg oral dose of alprazolam was combined with
steady-state levels of venlafaxine administered orally at 75 mg twice daily. The
levels of alprazolam in plasma and of alprazolam, alpha-hydroxyalprazolam, and 4
hydroxyalprazolam in urine were determined. Steady-state venlafaxine and O
desmethylvenlafaxine concentrations in plasma were reached before venlafaxine was
coadministered with alprazolam. Coadministering venlafaxine increased the
apparent oral clearance and volume of distribution of alprazolam by 36 percent
and 9 percent, respectively, and decreased the alprazolam area under the
concentration-time curve and half-life by 29 percent and 21 percent,
respectively. There were small but statistically significant increases in mean
baseline scores for the digit-symbol substitution and symbol copying tests,
probably reflecting a time-dependent learning effect. The maximum score decrease
from baseline for these two tests also increased, possibly representing an
additive effect of alprazolam and venlafaxine. Overall, venlafaxine did not
inhibit the CYP3A4-mediated metabolism of alprazolam in vivo, which corroborates
other in vitro and in vivo data showing a lack of CYP3A4 inhibition with
venlafaxine.
PMID- 9641004
TI - A controlled trial of venlafaxine in trichotillomania: interim phase I results.
AB - This article reports the preliminary findings of a two-phase trial examining the
efficacy of venlafaxine in trichotillomania. Phase 1 is a 12-week, open-label,
prospective trial of venlafaxine in trichotillomania. Venlafaxine was effective
in significantly reducing the symptoms of trichotillomania; 8 of 12 patients were
considered responders. The implications of the efficacy of venlafaxine in
trichotillomania are discussed, including its important advantages over other
available antidepressant and anxiolytic medications.
PMID- 9641005
TI - An open-label pilot study of fluvoxamine for mixed anxiety-depression.
AB - The syndrome of mixed anxiety and depression (MAD) has been described and is
familiar to both general psychiatrists and nonpsychiatrists. It was included in
the DSM-IV appendix as a syndrome proposed for further study. Fluvoxamine, a
selective serotonin reuptake inhibitor (SSRI) approved for the treatment of
obsessive-compulsive disorder, was studied for its effectiveness in treating
anxiety and depression simultaneously during an 8-week, open-label trial of
patients with MAD. Thirteen patients were included in the final, intent-to-treat,
analysis. Fluvoxamine showed moderately strong effectiveness in improving anxiety
and depression with a greater effect on the depressive component. Nausea,
insomnia, delayed ejaculation, and nervousness were the most common side effects
reported, with no serious adverse events occurring. Future double-blind placebo
controlled studies will give more conclusive results.
PMID- 9641006
TI - Interclass drug effects and changes in regional brain glucose metabolism.
AB - We have developed an innovative use of positron emission tomography that has
broad applications in drug development. Based on the FDG method (Phelps et al.
1979) for assessing glucose metabolism, the method requires rigorous experimental
control of subjects and standardized data acquisition and analyses. In localizing
net metabolic drug effects, measured in quantifiable terms, we have derived a new
conceptual basis for examining pharmacologically induced changes in brain
function and a new model for predicting drug effectiveness. We applied this
method to studies of drugs in three different classes and noted marked
differences in distribution and magnitude of metabolic effects. This approach
presents an opportunity to selectively examine measurements of the glucose
metabolic changes induced by specific pharmacological probes on intermediary
metabolic pathways, including regulation of gene expression and the metabolic
consequences of neurotransmitter alteration in pharmacologically targeted
neuronal systems. Development of these methods provides new approaches for
studying neurobiological mechanisms, and can contribute significantly to the
process of new drug development.
PMID- 9641007
TI - [The overshoot of the ST segment during exertion: a sign of the severity of the
pathology of the coronary arteries].
PMID- 9641008
TI - [How I treat colorectal cancer. I. Prevention and adjuvant treatment].
AB - Colorectal adenocarcinoma is a major cause of cancer-related morbidity and
mortality in Belgium and in other western countries. Prevention implies a
modification of alimentation and maybe a chronic uptake of acetylsalicylic acid.
Treatment of colorectal cancers is based on surgery and the prognosis is
determined by the locoregional or metastatic tumor spread. Complete resection of
any Astler Coller stage C colorectal malignant tumor has to be followed by a 5
fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is
administered together with folinic acid or levamisole. The administration of an
adjuvant chemotherapy could also be considered for stage BII diseases. As rectal
cancers are characterized by high local relapse rates, their treatment should
associate radiotherapy, given either post-surgery or preferentially pre-surgery,
with resection and chemotherapy. Appropriate treatment of colorectal cancers thus
requires a concerted multidisciplinary approach.
PMID- 9641009
TI - [Clinical case of the month. Galloping nephropathy in a patient with type 2
diabetes].
AB - We report the case of a patient with insulin-requiring type 2 diabetes who
exhibited a rapid deterioration of his renal function leading to haemodialysis in
a few months. Various diagnosis were considered to explain this rapid
deterioration, excluding diabetic nephropathy as major etiology. The exploration,
especially renal biopsy, demonstrated the presence of a glomerulonephritis due to
the deposition of immune complexes associated to active hepatitis C rather than
diabetic glomerulosclerosis. A treatment with interferon-alpha allowed to
partially restore renal function, this recovery permitting the interruption of
hemodialysis, with a current follow-up of more than 6 months.
PMID- 9641010
TI - [Osseointegrated endosseous implants, University of Liege concepts. Various
clinical applications].
AB - Based on fundamental experimental studies performed by the research teams of
Professor Branemark (Goteborg, Sweden), the use of dental implants has become a
scientifically accepted treatment concept in Dentistry to replace lost or missing
teeth in fully and partially edentulous patients. The use of dental implants was
initiated by the discovery that dental implants made of titanium can be anchored
in the jawbone with direct bone contact (osseointegration).
PMID- 9641011
TI - [Dermoscopy: magnified imaging of pigmented cutaneous tumors].
AB - The early clinical identification of malignant melanoma is important. Pigmented
neoplasms are sometimes difficult to diagnose by visual inspection alone.
Dermoscopy increases the reliability of the clinical assessment. Dermoscopic
criteria of malignancy are well defined on a descriptive ground. They allow an
optimal interpretation of the clinical aspect without, however, reaching the
sensitivity and specificity of the microscopic examination.
PMID- 9641012
TI - [Surgery of esophageal cancer in Liege. I. A study of mortality and perioperative
morbidity].
AB - BACKGROUND: To assess surgical outcome after oesophagectomy, we reviewed
operative techniques and postoperative course among 90 patients who underwent
oesophageal resection for malignancies from January 1989 to December 1995.
METHODS: There were 73 males and 17 females; mean age was 64.2 years. Indications
were squamous cell carcinoma in 49 patients and adenocarcinoma in 41.
Preoperatively 7 patients had chemotherapy and 18 benefited from
radiochemotherapy. There were 56 total thoracic oesophagectomies, with
anastomosis in the neck in 34 patients and at the thoracic inlet in 22. In 34
cases operation was limited to distal oesophageal resections. Digestive
continuity was restored with the stomach in 62 patients, with the colon in 24,
and with a jejunal loop in 4. A feeding jejunostomy was constructed in 48
patients with a gastric transplant. RESULTS: Mortality was 10% (9 patients),
decreasing from 18.5% (before 1993) to 3.8% (since 1993). One patient died in the
colonic graft group and 8 in the gastric pull-up group. Postoperative
complications occurred in 9 patients after colonic interposition and in 23 after
gastric pull-up; they consisted in pulmonary infection or insufficiency in 26
patients, cerebrovascular accident in one, renal insufficiency in 2, recurrent
nerve palsy in 4, and anastomotic leakage in 6. Transhiatal approach was not
associated with a decreased incidence of postoperative deaths or complications.
Eighteen patients (72%) developed postoperative pulmonary complications after
preoperative chemotherapy. CONCLUSION: Oesophagectomy can be performed with low
mortality. A colonic graft is not associated with an increased incidence of
perioperative deaths or complications and is the substitute of choice when there
is any question regarding gastric vascularization, or in young patients with long
life expectancy. Preoperative neoadjuvant treatment significantly increases
postoperative pulmonary complications.
PMID- 9641013
TI - [Dysfunction of the sphincter of Oddi in cholecystectomy patients].
AB - Sphincter of Oddi dysfunction (SOD) is an obstructive syndrome of the papilla not
resulting from a stone. It may cause recurrent biliary type pain to
cholecystectomized patients. SOD is caused by sphincter dyskinesia or benign
stenosis. Diagnosis is usually based on symptoms, serum biochemistry, endoscopic
retrograde cholangiopancreatography and Sphincter of Oddi manometry. The latter
is the best means of evaluating Sphincter of Oddi dynamics. However, because of
the many inconveniences of Sphincter of Oddi manometry and of its high morbidity
rate, it is seldom used. Non invasive techniques, such as cholescintigraphy, have
been developed to replace Sphincter of Oddi manometry in diagnosing SOD. Patients
can be cured by sphincterotomy. Certain drugs could also be effective but few
controlled studies have been carried out of date.
PMID- 9641014
TI - [Long QT syndrome: from clinical discovery to molecular etiopathogenesis].
AB - Before the era of Molecular Biology the etiopathogenic mechanism of the long QT
Syndrome (LQTS) was hypothetized to be an inhomogeneity in the innervation of the
myocardium by the sympathetic system resulting in abnormal myocardial
repolarisation, prolongation of the QT interval and various rhythm disorders. The
progress of Molecular Biology has led to abandon this hypothesis; it is now
agreed that the etiopathology of the various forms of the LQTS and of the
arrythmias which are associated with it lies in the presence of mutations
localized on genes coding either for cardio-specific ionic channels or for
proteins which modulate the activity of these ionic channels. Thus, the
alterations, direct or indirect, of these cardio-specific ionic channels lead to
a delayed repolarization of myocardial cells which manifest itself on the
electrocardiogram by a prolongation of the QT interval. This delayed
repolarization of myocardial cells would induce a reactivation of myocardial
ionic channels of the L-Ca++ type which leads to the development of secondary
late depolarization which represent the underlying cellular mechanisms for
"torsade de pointes". This hypothesis is experimentally reinforced by the
observation both in animals and in men of a prolongation of the QT interval as
well as aspecific tachyarrythmias after pharmacologic blockade of myocardial
potassium channels. Therefore the long QT syndromes probably find their origin in
genetic abnormalities of the electro-ionic system of the heart whereas the
mechanical function and the autonomic innervation appear to be entirely normal.
PMID- 9641015
TI - [Transdermal replacement hormone therapy: a trend or an advantage?].
AB - This review describes the clinical usefulness of transdermal hormone replacement
therapy. This route of administration is particularly important in women with
hypertriglyceridemia, in hypertensive postmenopausal women, in women who smoke or
have an increased risk of biliary or liver disorder, for those who display a
reduced glucose tolerance or in women who are at risk of thrombotic disorders.
The avoidance of the "first passage effect" is ensured by the transdermal
application of estrogen and probably explains the superiority of this route of
steroid administration.
PMID- 9641016
TI - [Cancer of the breast: mass screening by mammography is not justified].
AB - Mass mammographic screening for breast cancer is, for some, obviously beneficial.
For others, it is not justified in countries like ours and could even entail
deleterious consequences. This "controversy" exposes the views and justifications
pro and contra.
PMID- 9641017
TI - [Mass screening of breast cancer: response and justification].
PMID- 9641018
TI - [Medico-legal aspects of occupational deafness. Update 1998].
AB - The author gives new information on medicolegal sight of professional deafness in
relation to his paper published in this review in 1995.
PMID- 9641019
TI - [How I study the assessment of the risk of sudden death in Wolff-Parkinson-White
syndrome].
AB - The identification of a WPW impose to evaluate the potential risk of sudden
cardiac death. The risk depends on the duration of the refractory period of the
accessory pathway. If the preexcitation disappears when the patient is stressed
on a treadmill, there is no risk of sudden death. If it does not, an
electrophysiological study will have to be performed to measure the refractory
period of the accessory pathway. If a risk of sudden death is present (refractory
period < 220 ms), the accessory pathway has to be ablated using radiofrequency.
PMID- 9641020
TI - [Drug clinics. The drug of the month. Alendronate (Fosamax)].
AB - Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate which
inhibits bone turnover by suppressing the activity of osteoclasts without
increasing the risk of osteomalacia. Alendronate is highly effective at
preventing bone loss associated to absence of endogenous estrogen and induces a
sustained increase in bone mass. Fosamax is indicated and reimbursed in the
treatment of osteoporosis in postmenopausal women, with either an history of bone
fracture confirmed by X-ray exam or obvious osteoporosis assessed by bone mineral
density measurement. The recommended dosage is 10 mg once daily, continuously.
The drug should be absorbed after an overnight fast to improve its
bioavailability and with a big glass of plain water to reduce the risk of
oesophageal ulcerations. Large randomized controlled trials for up to 3 years
have demonstrated that alendronate is able to reduce the risk and rate of
occurrence of vertebral and nonvertebral fractures in postmenopausal women.
PMID- 9641021
TI - [Info-congress. Bisoprolol in congestive heart failure].
PMID- 9641022
TI - [Prevention of breast cancer using tamoxifen].
PMID- 9641023
TI - Biliary microliths--a lot of sound for small stones.
PMID- 9641024
TI - Veno occlusive disease.
PMID- 9641025
TI - Complications of acute pancreatitis.
PMID- 9641026
TI - Biliary microlithiasis.
PMID- 9641027
TI - Helicobacter pylori in dyspeptic Jordanian patients.
AB - To study the prevalence of Helicobacter pylori infection in dyspeptic Jordanian
patients. PATIENTS AND METHODS: Two hundred and twenty seven consecutive
dyspeptic Jordanian patients were studied with endoscopy, endoscopic biopsies,
culture, and CLO urease testing for the detection of H. pylori. RESULTS:
Helicobacter pylori positivity in both culture and CLO urease testing was 86%,
being 78% in culture and 80% in CLO test separately. The majority of our patients
were in the age range 21-60 years and H. pylori positivity was more than 90% in
them. CONCLUSION: Helicobacter pylori is a common infection in dyspeptic
Jordanian patients regardless of the underlying cause. Males were affected more
than females.
PMID- 9641028
TI - Helicobacter pylori infection in patients with perforated duodenal ulcer.
AB - AIM: Perforation is the commonest complication of duodenal ulcer. Helicobacter
pylori is found in 95% patients with duodenal ulcer. However, there is paucity of
reports on prevalence of H. pylori infection in patients with duodenal ulcer
perforation. We, therefore compared the incidence of H. pylori infection in
patients with duodenal ulcer perforation with the incidence in patients having
complicated duodenal ulcers and non-ulcer dyspepsia. PATIENTS AND METHODS: The
study was conducted on 45 patients (complicated duodenal ulcer 15, duodenal ulcer
perforation 15, non-ulcer dyspepsia 15). Per-operative punch antral biopsies were
taken in patients with duodenal ulcer perforation whereas endoscopic punch
biopsies of antrum were taken in patients with non-ulcer dyspepsia. The criteria
for H. pylori positivity was i) growth of H. pylori on culture, ii) combination
of rapid urease test (RUT) and Giemsa staining, combination of RUT and Gram stain
being positive for H. pylori. RESULTS: While 9 of 15 cases with complicated
duodenal ulcer, 7 of 15 cases with non-ulcer dyspepsia were positive for H.
pylori, none of the patients with duodenal ulcer perforation tested positive for
H. pylori (p < 0.000). All patients with perforated duodenal ulcer had
histological gastritis (H. pylori -ve). Fourteen of 15 patients (9 H. pylori +ve,
5 H. pylori -ve) with complicated duodenal ulcer and 9 of 15 patients (7 H.
pylori +ve) with non-ulcer dyspepsia had histological gastritis. CONCLUSION:
Patients with duodenal ulcer perforation do not have H. pylori infection. H.
pylori negative patients of duodenal ulcer may have more predilection for
perforation.
PMID- 9641029
TI - Is vegetarianism a precipitating factor for gallstones in cirrhotics?
AB - AIM: To study the association of factors such as alcohol, smoking and
vegetarianism with presence of gallstones amongst cirrhotics. PATIENTS AND
METHODS: Data on alcoholism, smoking and vegetarianism was collected from the
case records of 669 cirrhotics with (76) or without gallstones (593)
retrospectively. Relative risk for the factors was computed individually and in
combination controlling for the effects of alcoholism and smoking on
vegetarianism. RESULTS: Alcoholism and smoking were of low relative risk [R.R
1.27 (95% CI 0.82 to 1.96), and 1.02 (95% CI 0.65 to 1.61) respectively] while
vegetarianism was associated with high risk for gallstone formation in cirrhotics
[R.R 2.74 (95% CI 1.65-4.53)]. Vegetarian men had a relative risk of 3.02 (95% CI
1.75-5.22) irrespective of their alcoholic status. If women were alcoholic the
relative risk increased to 7.03 (95% CI 3.26-15.12). Controlling for effects of
gender and alcoholism, vegetarian cirrhotics had a 3 times greater risk for
gallstone formation [Mantel Haenszel Relative Risk 3.18 (95% CI MHRR 1.82-5.56)].
CONCLUSIONS: Cirrhotic, vegetarian women in South India have a much higher risk
for gallstones, if they are alcoholic. Alcoholic men who are vegetarians are at a
greater risk for gallstone disease.
PMID- 9641030
TI - Malignant jejunal polyp in Peutz-Jeghers syndrome.
PMID- 9641031
TI - When a hepatologist develops hepatitis!
PMID- 9641032
TI - Adjuvant preoperative radiotherapy for resectable rectal cancer. Do we have an
answer now?
PMID- 9641033
TI - Management of foreign bodies of the upper gastrointestinal tract.
AB - The use of flexible endoscopes had made removal of foreign bodies in the upper
gastrointestinal tract easier and safer. We describe our experience of 49 cases
of foreign bodies of the upper gastrointestinal tract. Majority (67%) of the
patients were children and only 4 patients (8%) were above 45 years of age. The
most common foreign bodies encountered were coins (25), fruit stones (4) and
dentures (3). In 29 patients foreign bodies were lodged in the oesophagus and in
15 cases in the stomach. Forty one patients were considered for endoscopic
removal of the foreign bodies and 40 could be managed successfully. There were no
procedure related complications. We conclude that endoscopic removal of the
foreign bodies of the upper gastrointestinal tract is a safe and effective
technique.
PMID- 9641034
TI - Hepatitis B and hepatitis C in multitransfused children.
AB - The study was conducted on 75 multitransfused children aged between 2 and 13
years who attended the Department of Paediatrics, LNJPN Hospital, New Delhi from
July 1990 to July 1991. These included 64 cases of thalassaemia major, 4 cases of
haemophilia, 3 patients of acute lymphatic leukaemia and one each of acute
myeloid leukaemia, aplastic anemia, chronic idiopathic thrombocytopenic purpura
and acute haemorrhagic pancreatitis. HBsAg was tested in all, Anti-HBc was tested
in 44 patients and Anti-HCV in 43 patients. Anti HDV was tested in HBsAg positive
patients and IgM anti-HAV was tested in patients suffering from hepatitis. Liver
function tests were evaluated in all patients. HBsAg was positive in 31% of
patients; 40% of males and 15% of females were HBsAg positive, the difference
being statistically significant. 84% of patients were Anti-HBc positive, 21% were
anti HCV positive, 4% were Anti HDV positive. 15% of the patients had post
transfusion hepatitis. Anti HCV was present in 57% of the hepatitis patients;
none had anti-HAV IgM.
PMID- 9641035
TI - Malignant gastroparesis and outlet obstruction in carcinoma gall bladder.
AB - INTRODUCTION: Malignant gastroparesis and mechanical gastric outlet obstruction
are two major accompaniments of advanced upper abdominal malignancies. The
incidence of such problems has not been well documented in patients of carcinoma
gall bladder. The aim of this study was to determine the incidence of gastric
outlet problems in patients of carcinoma gall bladder and correlate them with
clinical presentation. The role of prophylactic gastrojejunostomy (GJ) and its
postoperative outcome was also evaluated. PATIENTS AND METHODS: Thirty seven
patients of carcinoma gall bladder were prospectively studied. Twenty five
patients underwent radio labelled solid meal gastric emptying study and eleven of
these underwent prophylactic GJ and followup gastric emptying study in early
postoperative period. RESULTS: Mechanical gastric outlet obstruction was seen in
10 (27%) patients. Delayed gastric emptying on scintigraphic study was found in
10 (40%) of remaining patients (n = 25). Only 6 (60%) of these patients were
actually symptomatic. All patients who had delayed gastric emptying also had an
advanced disease. No correlation was found between delayed gastric emptying and
presence of jaundice and/or serum levels of bilirubin. Prophylactic GJ had 18%
postoperative morbidity as compared to 28.5% for therapeutic GJ done during the
same period. Oral feed were started latest by 11th postoperative day.
Prophylactic GJ did not affect gastric emptying patterns in early postoperative
period. CONCLUSION: Mechanical gastric outlet obstruction was present in 27%
patients. Delayed gastric emptying was seen in 40% of remaining patients with
carcinoma gall bladder. Delayed gastric emptying correlated well with symptoms of
gastric stasis and the stage of disease. Functioning of gastrojejunostomy was not
fully dependent on presence or absence of malignant gastroparesis.
PMID- 9641036
TI - [Treatment of alcohol abuse].
PMID- 9641037
TI - [Epidemiology of hepatitis C].
PMID- 9641038
TI - [Hereditary long QT syndrome].
AB - The Long QT Syndrome (LQTS) is a hereditary disease, characterized by a prolonged
QT-interval on the electrocardiogram and a high risk of syncope and sudden death
due to ventricular arrhythmias. LQTS must be suspected in apparently healthy
children and young people with syncope after emotional or physical stress.
Untreated symptomatic patients have a high mortality, which is markedly reduced
by sympathetic block. The knowledge of the diagnostic criteria for the LQTS, a
detailed history including a family history and an ECG-recording with measurement
of the QT-interval in every patient with inexplicable syncope will advance the
diagnosis of the LQTS and improve the survival of these patients after proper
therapy. The current knowledge on the molecular genetics, epidemiology,
mechanisms of arrhythmias and therapy are presented with special emphasis on the
defects in the control of ionic transport over the cell membrane caused by
mutations in ion channels.
PMID- 9641039
TI - [Lung physiotherapy as prophylaxis against atelectasis and pneumonia after
abdominal surgery].
AB - Postoperative pulmonary complications play a significant role for the
postoperative morbidity after abdominal surgery. To prevent this, an array of
methods, such as lung physiotherapy, incentive spirometry, or mask treatment with
positive airway pressure are used. The available controlled studies indicate that
none of these treatment modalities reduce the occurrence of postoperative
atelectasis, but only lung physiotherapy is able to reduce the development of
postoperative pneumonia. Thus, we recommend lung physiotherapy as prophylactic
treatment after abdominal surgery. The value of optimized pain alleviation and
mobilisation in addition to lung physiotherapy should be evaluated in future
trials.
PMID- 9641040
TI - [Antabus treatment in general practice. A pharmaco-epidemiological study of
prescription patterns based on a prescription database].
AB - Denmark has a long tradition for the use of alcohol-aversive drugs in the
treatment of alcoholism, most commonly disulfiram (Antabuse). The purpose of this
study was to examine the prescription patterns for disulfiram in Danish general
practice on an individual level. By means of a prescription database we analysed
150,787 prescriptions on reimbursed medicine to persons who had redeemed
prescriptions for alcohol-aversive drugs during the period 1.1.1993 to 31.12.1995
in the County of Funen. Prevalence of disulfiram treatment was 12 per 10,000
inhabitants, three-year prevalence 75 per 10,000 inhabitants and incidence 21 per
10,000 inhabitants per year. Eighty-seven percent of treatments were stopped at
(or before) the expiration of one prescription, and relapse was frequent (46%).
PMID- 9641041
TI - [Detoxication in hospital contra detoxication in detention].
AB - In the present study, 61 persons taken into police custody due to drunkenness
were compared with 57 persons admitted to hospital due to intoxication with
alcohol. The persons with alcohol problems taken into police custody numbered
more younger men, fewer retired persons and the alcohol problems were more often
acute intoxication than alcohol dependence. None of the persons placed in police
custody were advised to seek help for their alcohol problems in contrast to 45
out of the 57 admitted to the hospital who started treatment. Detoxification in
hospitals is far more suitable to motivate persons with alcohol problems to seek
help. Detoxification should, for non criminal intoxicated people, be performed in
hospitals.
PMID- 9641042
TI - [Factors related to suicidal behavior among alcoholics].
AB - Of 181 alcoholics who consecutively sought treatment as out- or inpatients, 68
(37.6%) had attempted suicide at least once. Compared with non-attempters, the
suicide attempters were significantly more likely to be female, have had a
chaotic upbringing and to have known suicide attempts in the family and social
circle. Significantly more attempters suffered from depressive disorder, feelings
of hopelessness, anxiety attacks, agoraphobia, substance abuse or cluster B
personality disorders (dissocial, impulsive, borderline, and histrionic). Also
significantly more suicide attempters had committed crimes and received early
pension. Assessment of coping showed that suicide attempters had a significantly
lower tendency to make plans or to make the best of a stressful situation by
growing from it. They were significantly more likely to show mental
disengagement, to resort to denial and drink alcohol or take drugs when faced
with stressful events or difficulties. When evaluated on the Addiction Severity
Index Scale, the suicide attempters were found to have a significantly greater
need of treatment.
PMID- 9641043
TI - [Computer assisted neuropsychological testing of children].
AB - The purpose of the study was to examine the feasibility of a computer-assisted
neuro-psychological test program, the Neurobehavioral Evaluation System (NES), in
six to seven year-old children. We administered three NES tests, Finger Tapping
(FT), Continuous Performance Test (CPT) and Hand-Eye Coordination (HEC) to
Faroese and Danish children. The FT and CPT were of appropriate difficulty, while
the HE was too difficult for the majority of the children. Boys obtained better
scores than the girls, and children who were familiar with computers and video
games performed better than those without such experience. Older children also
obtained better scores than younger ones, especially in the Faroese group. The
Danish children performed better than the Faroese in FT and CPT. In HE there was
no difference. The NES tests are feasible for children at this age, but
appropriate comparison groups must be secured.
PMID- 9641044
TI - [Mortality and worsening of prognosis for patients with aortic stenosis while on
the waiting list].
AB - In a prospective study, 99 consecutive patients with an operative indication due
to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting
time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There
were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients
were divided into three groups: group 1 (N = 81) with an uneventful stay on the
waiting list; group 2 (N = 11) with significant worsening of a prognostic index;
and group 3 (N = 7) with patients who died during the waiting time. The waiting
list death rate was 13.5%/patient-year compared with a post-AVR death rate of
4.9% patient-year (p < 0.05) with a mean post-AVR follow-up of 5.7 years.
According to a prognostic index (Cox regression model) at inclusion, group 2
patients had a predicted 7-year post-AVR survival probability of 72%, but only of
61% according to their prognostic index immediately preoperatively; their
observed 7-year post-AVR survival was 60%. Logistic regression analysis
identified high age, short duration of symptoms, signs of severe hypertrophy and
strain in the ECG, female gender, and deranged left ventricular diastolic
function (related to severely increased left ventricular muscle mass) as
independent predictors of prognostic worsening and death while on the waiting
list. The predictive models did not allow sufficiently accurate identification of
the patients at risk during the waiting period. The consequences of a surgical
waiting period averaging 6 months are serious for AS patients. The death rate is
high and a subgroup worsens its prognostic profile with a significantly reduced
post-AVR long-term survival as the result.
PMID- 9641045
TI - [Segond fracture in acute knee injuries].
AB - Two patients with a lateral tibia avulsion fracture (Segond fracture) are
presented. The correlation between the Segond racture and rupture of the anterior
cruciate ligament is pointed out, as well as the fact that patients with Segond
fracture and rupture of the anterior cruciate ligament often have other injuries
such as meniscus lesions and lesion of the medial collateral ligament.
PMID- 9641046
TI - [Combined nitroglycerin-heparin infusion in mesenteric venous thrombosis].
AB - Surgical treatment of venous mesenterial thrombosis (VMT) may result in a short
bowel-syndrome. We report the successful outcome of combined intravenous heparin
and nitroglycerine in a case of VMT followed by a limited resection of small
bowel.
PMID- 9641047
TI - [Screening for colorectal cancer--diminishing number of emergency admissions?].
PMID- 9641048
TI - [Meta-analyses to reveal insufficient mega-trials].
PMID- 9641049
TI - [Contribution to anticholesteremic agents?].
PMID- 9641050
TI - [Reteplase. A new thrombolytic agent in the treatment of acute myocardial
infarction].
PMID- 9641051
TI - [Authorship of scientific articles].
PMID- 9641052
TI - [Endogenous retroviruses in the human genome].
PMID- 9641053
TI - [Reliability of the epidural test dose].
AB - Complications associated with epidural anaesthesia include accidental
intravascular or subarachnoid epidural catheter misplacement resulting in
systemic toxicity and total spinal block, respectively. Epidural test doses are
used routinely to prevent these events. It is not known whether the use of test
doses improves the safety of epidural anaesthesia. The reliability of the
epinephrine test dose in terms of detecting intravascular injection is impaired
in elderly patients, patients receiving beta-blockers, patients undergoing
vascular surgery, patients under general anaesthesia, and in women in labour. The
ability of the epidural test dose to detect subarachnoid injection remains
unknown. Studies are needed to determine 1) the reliability of the epidural test
dose among different groups of patients, 2) the safety of the test dose, and 3)
the incidence of epidural catheter misplacements.
PMID- 9641054
TI - [Shoulder instability].
AB - The importance of the labrum and glenohumeral ligament complex for the stability
of the shoulder joint has been known since the beginning of this century.
Shoulder instability may be classified into two large groups. TUBS, characterized
by Traumatic, Unidirectional instability and Bankart lesion which often requires
Surgery. The second group AMBRI, is characterized by Atraumatic,
Multidirectional, Bilateral instability that often responds to Rehabilitation,
but in case of surgery Inferior capsular shift is indicated. The high recurrence
rate after primary traumatic anterior dislocation in young adults has caused an
ongoing discussion about the indications for primary surgery. Anatomical
reconstruction focusing on the pathoanatomy is recommended due to better results
and a lower complication rate as compared to non-anatomical reconstruction that
alters the normal anatomy and kinematics. The recurrence rate after arthroscopic
Bankart repair is still generally higher than after open surgery but may be
improved by better patient selection.
PMID- 9641055
TI - [Balloon dilatation of congenital aortic stenosis].
AB - We evaluated the catheterization results and follow-up echocardiographic data in
all (n = 31) patients undergoing balloon dilatation for congenital aortic valve
stenosis at Skejby University Hospital from May 1987 to October 1996. Patients
were between three weeks and 35 years of age (median 12.1 years). Peak-to-peak
systolic pressure gradient was reduced by 59%, from 74 +/- 17 to 30 +/- 20 mmHg
(p < 0.0001). Balloon valvuloplasty was successful in 26 (84%) patients. At
follow-up 38 +/- 33 months after balloon valvuloplasty, 19 of these 26 patients
(73%) had a persistent reduction in gradient compared with that before
valvuloplasty. In the seven patients who had been operated during the follow-up
period, balloon valvuloplasty had delayed surgical intervention by 6-97 (median
38) months. Balloon valvuloplasty is an effective, low risk palliative procedure
in patients with congenital aortic valve stenosis.
PMID- 9641056
TI - [The frequency of secondary cataract after extracapsular cataract extraction].
AB - A complication of extracapsular cataract extraction is posterior capsule
opacification (secondary cataract). In this study we found that 26.0% of patients
operated for cataract with extracapsular technique were treated for secondary
cataract. The average postoperative time to treatment with Nd-YAG
lasercapsulotomy was 15.2 months with a follow-up time of 34 months.
PMID- 9641057
TI - [Brain damage in relation to occurrence of retinopathy of prematurity. A regional
ophthalmologic follow up of premature infants born 1982-1984].
AB - Regular ophthalmic surveillance started in 1982 for all surviving prematures in
Frederiksborg County considered at risk of developing retinopathy of prematurity
(ROP). During 1982-1984 185 infants of gestational age 25-35 weeks at delivery
were examined; blindness eventually appeared in four out of the 28 who showed
some stage of ROP. All 28 attended ophthalmic reassessment at age 7-10 years and
were compared with 60 of the same cohort without evidence of ROP. At follow-up (n
= 88) there was evidence of psychomotor disturbances in 45 children, manifesting
as major CNS damage in 21, and minor in 24. With correction for drop-outs the
regional frequency of severe CNS damage (mainly cerebral palsy and mental
retardation) was 29.6% for gestational ages < 32 weeks at delivery and 24% as
calculated for birth weights < 1500 g. An analysis of perinatal factors based
mainly on matched pairs did not indicate any definite association with subsequent
damage to eye or brain, and statistically there was no association between
severity of ROP and CNS impairment. We have no explanation for the high frequency
of CNS impairment at follow-up.
PMID- 9641058
TI - [Cryotherapy of retinal prematurity in Denmark 1992-1996].
AB - Retinopathy of prematurity (ROP) is a vasoproliferative disorder often met in
infants of very preterm delivery. Lower stages usually regress spontaneously, but
progression to so-called threshold-ROP should lead to anterior retinal ablation
therapy, by cryopencil or laser. Fifty-three Danish infants born 1992-96 were
evaluated in the University eye clinic of Rigshospitalet for the disease; 65 eyes
of 36 infants had cryotherapy; eight infants developed severe bilateral visual
handicap (22%). The reason for not giving cryotherapy to the remaining 17 was:
too late referral in five, and ROP below threshold in 12; seven of the 17 later
appeared in the (mandatory) national register for childhood visual handicap.
Perusing these data the other way round, 15 of the registered 18 cases were thus
known to us, while three had escaped referral. With reservation for the small
numbers included, the national trend at present is an increasing annual number of
subjects receiving retinal ablation therapy for ROP, and a decrease in severe
visual impairment due to the disorder. Obviously all preterm infants at risk
should be under early regular ophthalmic surveillance for ROP.
PMID- 9641059
TI - [Conjunctival nevi in Denmark 1960-1980. A 21-year follow-up].
AB - The clinicopathological characteristics of 343 naevi of the conjunctiva were
studied. A significant increase in the number of naevi excised per year was
observed. This may have been caused by an increased exposure to actinic rays. An
approximately even distribution was found between the three main locations:
caruncle, limbal area and eye ball. Intrastromal naevi were excised at a higher
median age than compound naevi, and the lowest median age at excision was for
junction naevi, which is in accordance with the known histopathological nature of
naevi. Recurrence occurred in nine patients (2.7%), and one had transformed into
a malignant melanoma. Eight of the recurring naevi were located in the limbal
area. Eight of the nine patients were women, suggesting hormonal factors as a
possible cause. Recommendations for the handling of conjunctival naevi are given,
based on the present findings and on previous reports.
PMID- 9641060
TI - [Significance of idiopathic preterm birth in relation to previous and future
pregnancies].
AB - This registry-based cohort study aimed to describe the relationship between
pregnancy complications in the first and second pregnancy, focussing on
idiopathic and indicated preterm birth of singleton infants in either pregnancy.
The cohort consisted of all women living in Denmark with a first singleton birth
in 1982 and a second in the period 1982-1987 (13,967 women). The risk of a second
preterm birth was not significantly different between women who had an idiopathic
or an indicated first preterm birth (15.2 and 12.8% respectively). Adjustment by
logistic regression analysis for other risk factors for preterm birth did not
influence the relative risk (6.0 before 32 weeks and 4.8 between 32 and 36 weeks)
of a second preterm birth subsequent to a first one. Women with idiopathic
preterm delivery in their first or second pregnancies give birth to infants with
lower birth weight in previous or subsequent pregnancies. Emergency cesarean
section in a first term pregnancy was a risk factor for subsequent idiopathic
preterm birth.
PMID- 9641061
TI - [Increased concentration of Na,K-pumps in skeletal muscles of patients with
chronic obstructive lung disease. Significance of magnesium depletion and
treatment with glucocorticoids].
AB - Patients with COLD may develop Mg depletion due to inadequate nutrition or
treatment with diuretics and beta 2-agonists. In 36 consecutive COLD patients
skeletal muscle concentrations of Mg and K were reduced by 22% and 14%,
respectively, compared to 23 age- and sex-matched controls (p < 0.001). Patients
receiving diuretics showed a further reduction of muscle Mg (-31%) and K (-27%)
compared to controls. The mean concentration of Na,K pumps was increased by 31%
(p < 0.001), while a more pronounced increase (+61%) was seen in 12 intensive
care patients receiving high dosages of glucocorticoids. Thus muscle
concentrations of Mg and K are reduced in COLD patients and are associated with
an upregulation of the Na,K-pump concentration. It is plausible that this
upregulation may be caused by glucocorticoid treatment. The clinical benefits of
glucocorticoids may therefore in part be due to an increased activity and
capacity of the Na,K-pump and thereby in a possible enhancement of muscle force.
PMID- 9641062
TI - [Amyl nitrite poisoning].
AB - Two cases of amylnitrite poisoning are presented. In both cases, severe
methaemoglobinemia developed after ingestion of approximately 10 ml of
amylnitrite. When admitted to hospital, both patients were deeply cyanosed, and
arterial blood samples were noticed to be chocolate brown. They were
intravenously treated with methylene blue. Within one hour the condition of both
patients had improved dramatically, and blood gas-samples had normalised. In
cases of cyanosis with no obvious genesis, poisoning with amylnitrite should be
considered.
PMID- 9641063
TI - [Acute bacterial meningitis--NOSce te ipsum (know yourself)].
PMID- 9641064
TI - [Increased blood pressure should be efficiently treated. Results from the
Hypertension Optimal Treatment Study (the HOT-study)].
PMID- 9641065
TI - [Fibromyalgia].
PMID- 9641066
TI - [Develpment of asthma prevalence 1986-1992].
PMID- 9641067
TI - [More about ticks].
PMID- 9641068
TI - [More about ticks].
PMID- 9641069
TI - [More about ticks].
PMID- 9641070
TI - The Management of Intractable Pain Act: what will it mean for physicians and
patients in West Virginia?
PMID- 9641071
TI - Malaria in West Virginia: forty cases seen at West Virginia University Hospital.
AB - In the U.S., malaria predominately occurs in travelers and immigrants. We report
a series of 40 cases at West Virginia University Hospital, and 24 of whom were
students who had visited areas of East Africa, West Africa and Asia usually in
either December, January, August or September. Most patients (79%) reported a
previous episode of malaria, and P. falciparum was identified in 60%. Fever,
chills and rigors were the most common symptoms. Correct use of malaria
prophylaxis was recorded in five patients, and only two of these were students.
Successful outcomes were recorded in all but one patient. Our series suggests
that international students would benefit from the proper use of
chemoprophylaxis, thus decreasing the number of cases of malaria seen in
university settings.
PMID- 9641072
TI - A case report of idiopathic pulmonary ossification.
AB - Idiopathic pulmonary ossification is a rare disease. Most commonly, it affects
middle-aged men. Its etiology is unknown. We present a case of nodular type
idiopathic pulmonary ossification in a 42-year-old, white male who had one
episode of hemoptysis.
PMID- 9641074
TI - The organization of children's same-sex peer relationships.
PMID- 9641073
TI - Utilization of diagnostic resources for meningoencephalitis in the pediatric ICU.
AB - To determine whether a Pediatric Critical Care team has an evolution of medical
practice that decreases the utilization of diagnostic tests and consults, we
examined the records of 69 patients admitted for meningitis or
meningoencephalitis at Women and Children's Hospital in Charleston, W.Va., a
university-affiliated, teaching hospital. The study was conducted from August
1990 to August 1994. We found that utilization of diagnostic resources (UDR)
decreased over the four years, and there was a direct relationship between an
increase in severity of illness and an increase in UDR. When adjusted per
severity of illness, UDR decreased by $423 per year. The presence of a consult
was a factor leading to an increase in resources, which were associated with an
increased utilization of diagnostic tests and length of stay. The consultation
rate was independent of the severity of illness and experienced a decrease over
the years.
PMID- 9641075
TI - The popularity of friendship and the neglect of social networks: toward a new
balance.
PMID- 9641076
TI - Children's development within peer groups: using composite social maps to
identify peer networks and to study their influences.
PMID- 9641077
TI - The peer ecology of popularity: the network embeddedness of a child's friend
predicts the child's subsequent popularity.
PMID- 9641078
TI - Cardiovascular applications of lasers: searching for a niche.
PMID- 9641079
TI - Transmyocardial laser revascularization: historical background and future
directions.
AB - Transmyocardial laser revascularization (TMLR) was investigated as a possible
treatment alternative for patients with refractory coronary artery disease. This
paper is a summary of nearly four decades of research by the authors. Beginning
in 1969 experimental studies were conducted on the beating heart. A prototype 450
W carbon dioxide laser was used to create channels in the ischemic myocardium.
Initial clinical studies began in 1984. A protocol was developed for TMLR as an
adjunct to CABG in those patient who had at least one vessel which could be
bypassed and areas of ischemia which were not amenable to bypass. In the early
1990's the development of a 850 W CO2 laser for clinical use allowed us to begin
investigation of TMLR on the beating heart. Patients with end stage coronary
artery disease who were not candidates for other forms of treatment were
selected. The early results are encouraging with patient followup of from 3
months to 5 years. There are numerous controversies regarding the effects of TMLR
on myocardial function and perfusion. To quantify these effects the authors have
performed acute and chronic studies on swine using sophisticated techniques with
3D cine magnetic resonance imaging. We concluded TMLR improved left ventricular
function and perfusion in acute and chronic ischemia.
PMID- 9641080
TI - The physics of transmyocardial laser revascularization.
AB - Lasers create channels through the myocardium by ablating the tissue and tissue
ablation is achieved by breaking the molecular bonds of the organic constituents
of the myocardium. Lasers provide the energy required to dissociate these
molecular bonds by the interaction of laser photons with the tissue. However, the
energy supplied to the electrons within the bonds must match specific allowed
energy levels. Such energy matching is accomplished through different mechanisms
by different laser wavelengths. Infrared laser photons are strongly absorbed by
water in the tissue and it is the subsequent vaporization of the water that
provides the energy necessary to break the bonds. In contrast, ultraviolet laser
photons are not absorbed by water and have energies that can match those required
for bond dissociation. Thus, ablation by ultraviolet lasers is achieved primarily
by direct bond absorption of the photons. Both of these ablation mechanisms
produce secondary effects that can cause injury to tissue surrounding the
channels. The generation of steam or the gaseous breakdown products of tissue
proteins can cause thermal injury in addition to the mechanical injury produced
by escape of these gases into the tissue. Furthermore, shock waves generated by
ablation are also a possible source of mechanical injury, while free radical
molecules capable of cell injury are known to be formed after breaking chemical
bonds. The variety of tissue interactions provided by the different lasers should
enable the optimal laser treatment to be applied once the optimal channel
configuration has been determined.
PMID- 9641081
TI - Detection and assessment of laser-mediated injury in transmyocardial
revascularization.
AB - When channels are made through the myocardium with a laser, tissue surrounding
the channels is injured. Thus, methods of examining and quantifying the
histologic changes caused by laser-mediated injury are required both for
comparison of different channel making protocols and also to help understand the
mechanisms of transmyocardial revascularization. The two principal components of
the myocardium, collagen and muscle, are both normally birefringent. This optical
property can be exploited with the use of polarized light microscopy to assess
tissue structure at the cellular and subcellular levels allowing several
different types of injury to be detected. Increases in tissue temperature above
60 degrees C for muscle and 70 degrees C for collagen decrease their
birefringence and, hence, result in decreased brightness when viewed with
polarized light. Lower temperatures may cause cell membrane injury, calcium
overload, and the formation of contraction bands, which appear as areas of
increased birefringence. In this way, the extent of thermal injury can be
assessed. The same optical properties can be used to measure cell and fiber
orientation and, hence, enable assessment of mechanical disruption of the tissue
after ablation. Long-term remodeling of the myocardium in the form of scar
formation, increased interstitial fibrosis, and muscle disarray can also be
quantified. The ability to measure the acute injury and the long-term structural
consequences of that injury with the use of polarized light microscopy should
prove vital in determining the optimal laser "dose" required and may also reveal
information on the mechanism(s) of benefit found with transmyocardial
revascularization.
PMID- 9641082
TI - Angiogenesis: a possible mechanism underlying the clinical benefits of
transmyocardial laser revascularization.
AB - While clinical reports indicate that significant relief of angina is achieved
with transmyocardial laser revascularization (TMLR), the mechanisms of benefit
are still a matter of considerable controversy. Studies in our laboratory, as
well as in the laboratories of other investigators, have challenged the classic
hypothesis that benefits are derived from blood flow through chronically patent
channels. While several alternatives have been proposed, our work has focused on
investigating the possibility that TMLR stimulates vascular growth in the region
around the TMLR channels. We have performed studies looking at histologic markers
of vascular growth (including vessel counting and cellular proliferation assays)
in order to test this hypothesis, the results of which are reviewed. In brief, we
find that TMLR markedly enhances myocardial vascular growth above what is seen
normally in ischemic myocardium. We hypothesize that the underlying mechanism
relates to liberation of growth factors by inflammatory cells, which are
recruited in response to the laser induced myocardial injury. Clarification of
whether this mechanism contributes to observed clinical benefits is of
fundamental importance, since such understanding may suggest means of enhancing
the process.
PMID- 9641083
TI - Myocardial angiogenesis as a possible mechanism for TMLR efficacy.
AB - Despite advances in the treatment of ischemic heart disease, there still exists a
significant number of individuals for whom bypass surgery or angioplasty are not
options. Transmyocardial laser revascularization (TMLR) is a promising technology
that has already been shown to reduce symptoms in patients with chronic ischemic
heart disease that is not amenable to conventional therapies. Although it appears
that TMLR can provide symptomatic relief of angina in selected patients, the
mechanism by which TMLR is thought to work is unclear. Recently it has been
postulated that TMLR induces an angiogenic response and, perhaps, improves local
perfusion to ischemic myocardial territories. A brief overview of the biology of
myocardial angiogenesis is presented.
PMID- 9641084
TI - Clinical studies of TMR with the CO2 laser.
AB - OBJECTIVE: This paper reviews the current status of transmyocardial laser
revascularization by a carbon dioxide laser. SUMMARY: Since 1990 over 3000
patients worldwide have been treated with a carbon dioxide laser. A nonrandomized
phase II trial was completed in 1995. A randomized controlled phase III trial has
completed enrollment, and analysis of the follow-up is pending. METHODS: In each
trial 200 patients with endstage coronary artery disease and severe disabling
angina that was not amenable to conventional revascularization were enrolled.
Preoperative evaluation included confirmation of angina class and evidence of
reversible ischemia based on myocardial perfusion scans. Repeat evaluations were
done postoperatively at 3, 6 and 12 months. RESULTS: 80% of the patients showed a
significant improvement in angina class status postoperatively and 30% had no
angina at one year of follow-up. Concomitant with this there was significantly
less ischemia noted on follow-up perfusion scans. CONCLUSIONS: Early results from
nonrandomized and randomized controlled trials of transmyocardial laser
revascularization by carbon dioxide laser indicate that this technique provides
angina relief and improved perfusion in patients with end-stage coronary artery
disease.
PMID- 9641085
TI - Role for holmium:YAG lasers in transmyocardial laser revascularization.
PMID- 9641086
TI - Percutaneous transmyocardial revascularization.
AB - Transmyocardial revascularization (TMR) is a potential therapy for patients with
severe angina pectoris and coronary anatomy deemed unsuitable for traditional
revascularization techniques. Investigations of TMR are reviewed with emphasis on
studies relevant to the development of a percutaneous, catheter-based
transmyocardial revascularization procedure (PMR). The results of the preliminary
animal studies and description of the PMR procedure are discussed. The recently
initiated human PMR protocol is summarized and possible future investigative
directions are outlined.
PMID- 9641087
TI - Transmyocardial laser revascularization--a technique in evolution.
AB - Transmyocardial laser revascularization (TMLR) is a rapidly evolving technique
that represents the recent rediscovery of an old therapy. A growing clinical
experience is being assimilated into clear indications and contraindications for
and the appropriate performance of this procedure. This technique can be judged
to improve patient quality of life and survival in appropriately selected
patients. The therapy should still be applied cautiously, in that a full
understanding of its indications and mechanism of action remains in a state of
evolution.
PMID- 9641089
TI - Laser literature watch.
PMID- 9641088
TI - Transmyocardial laser revascularization: current experience and future direction.
AB - Transmyocardial laser revascularization (TMR) with the CO2 laser (PLC Medical
Systems, Inc., Franklin, MA) appears to improve the quality of life and event
free survival of end-stage coronary artery disease patients. Application of this
technology prior to clinical instability, along with diligent anesthetic support,
careful patient selection, and perioperative management, are essential to a
successful outcome. Rush-Presbyterian-St. Luke's Medical Center became the fifth
clinical site to investigate TMR under Phase II and Phase III U.S. Food and Drug
Administration (FDA) protocols. This clinical experience includes a total of
seventy-nine patients, of whom sixty-three had sole TMR utilizing a minimally
invasive approach on the beating heart. Lessons learned, to optimize patient
selection and operative- and postoperative management, will be delineated and the
future direction of TMR will be discussed.
PMID- 9641090
TI - A catalogue of anomalies and traits of the permanent dentition of southern
Chinese.
AB - Variations in size, form and morphology of the teeth can result in anomalies such
as macrodontia, microdontia, hyperdontia, hypodontia, double tooth, dens
evaginatus, dens invaginatus, and talon cusp. A trait may occur more commonly in
certain ethnic groups. Among these traits are shovel-shaped incisors, lingual
tubercle, Carabelli's trait and protostylid of the molars. Because people are
traveling more frequently than ever before, and there are many migrants in
different parts of the world, it is increasingly important for dental
professionals to be aware of the characteristics and prevalence of the anomalies
and traits that occur in the different ethnic groups, so as to be able to make
valid clinical judgments and to provide the appropriate treatment. The
characteristics of these anomalies and traits are presented along with the
prevalence figures in the southern Chinese.
PMID- 9641091
TI - The maxillary molar mesial sub-occlusal enamel web: identification of a
previously unreported tooth structure: the maxillary Rainey web.
AB - This article describes the anatomical structures of the suspensory web of enamel
in the area formerly known as the mesial "fossae," which has been assumed to be a
single "pit" and the area immediately adjacent mesially, formerly known as the
mesial marginal ridge "fossae." This structure lies anterior to the predominant
feature of the occlusal table of the maxillary first molars, the oblique or
transverse ridge, and distal to the mesial marginal ridge.
PMID- 9641092
TI - Children's sense of pleasure from nitrous oxide therapy during dental visits.
AB - The purpose of the present study was to measure feelings of pleasure by children
who were undergoing dental treatment under nitrous oxide therapy during
consecutive treatment sessions, and at a six-month follow-up visit. Fifty-two
children between the ages of 3 and 5 years (mean age 4.3 +/- 1.06) children, who
required two or more operative treatment visits participated in the study. At the
conclusion of the initial treatment and after sufficient time for the effects of
the nitrous oxide therapy to subside, patients were asked about their feelings
from the gas. At subsequent visits, patients were asked the same questions at the
beginning of each treatment session. The same was done at the beginning of a six
month follow-up visit. In general, there was a decrease in pleasure among those
who experienced three or more visits. Extraction, in addition to operative
treatment, did not result in a decrease in the sense of pleasure from nitrous
oxide therapy. A similar response was observed in the recall visits when the
reactions of the children were compared with the reactions at the last dental
appointment. It is concluded that the sense of pleasure is strengthened through
the second visit, but that the sense of pleasure and ability to cope is
overwhelmed by the inconvenience of the dental treatment at the third visit.
PMID- 9641093
TI - Minimizing otitis media by manipulating the primary dental occlusion: case
report.
AB - Acrylic resin bonded to the occlusal surfaces of mandibular second primary molars
was found to be an effective method to disclude the primary dentition and reduce
or eliminate otitis media in young children between the ages of two to six years
of age.
PMID- 9641095
TI - Ectopic eruption of maxillary first permanent molars: treatment options and
report of two cases.
AB - Irreversible ectopic eruption of maxillary first permanent molars may lead to
crowded permanent dentition when it is overlooked. The situation usually requires
active treatment. In the presented irreversible ectopic eruption cases,
distalization and uprighting of maxillary first permanent molars were achieved
using removable orthodontic appliances.
PMID- 9641094
TI - Open bite due to lip sucking: a case report.
AB - Lip sucking, in spite of being less frequent than other habits, can cause
malocclusion, which in turn may favor the appearance of other new habits such as
tongue thrust. The elimination of this habit can lead to the spontaneous
correction of malocclusion. The case report of a three-year-old male with a lip
sucking habit is presented. After eliminating the habit, the open bite that it
had caused, corrected spontaneously.
PMID- 9641096
TI - Bonding mechanism of Compoglass to dentin in primary teeth.
AB - This study evaluated the bonding mechanism of Compoglass compomer to dentin in
primary teeth. Buccal or labial dentinal surfaces of 20 human extracted, non
carious primary teeth stored in 4 degrees C physiological saline solution were
obtained by grinding on silicon carbide paper (final grit 600). The specimens
were divided into two groups of 10 teeth each: (1) unetched dentin, Compoglass
SCA, Compoglass; and (2) dentin etched with 10% phosphoric acid (Etch-AII),
Compoglass SCA, Compoglass. The Compoglass SCA and Compoglass compomer were
placed according to the instructions of the manufacturer, except Group 2 were the
dentin was first etched with 10% phosphoric acid for 30 seconds. Twenty-four
hours after placing the compomer over the treated dentinal surface, the specimens
were dehydrated with a series of alcohol and freon. Then critically point dried.
The specimens were split with a chisel and the compomer/dentin interface
evaluation was performed with the SEM. The results showed that when the
instructions of the manufacturer were followed (Group 1) the compomer showed a
very close relation to the dentin with some tag structures penetrating the
dentin. When phosphoric acid etching preceded the compomer placement a hybrid
layer with tags penetrating the dentin was noted in most specimens.
PMID- 9641097
TI - Microleakage reduction from newer esthetic restorative materials in permanent
molars.
AB - Through use of new technologies, such as air-abrasive devices, caries detector
dyes, modern technology can increase the speed, comfort and success of dental
restorations. However the issue of marginal adaptation has been an ongoing
technical problem. Today with the more frequent use of posterior composite
resins, poor marginal adaptation of resin is still the major cause of failure of
the restoration. Material contraction from polymerization and possibly
inappropriate preparation design are key factors in the longevity of the
restorations. This study attempts to determine the more effective material and
technique for reducing microleakage in composite restorations. An in vitro study
using three hybrid composite resins was done to evaluate marginal microleakage.
Extracted molars were chosen and evaluated for caries through the use of caries
detector dye. Using air-abrasion, caries were removed and minimal preparations
were done. The samples were divided into two groups. First group was restored
with Herculite XRV and Heliomolar paste composites resins. The second group was
restored with Revolution flowable composite resin. Also Opti-bond and Fortify
were used as a bonding agent and surface penetrating sealant respectively. The
teeth were properly finished, thermocycled and evaluated for leakage using 2%
basic fuschin detector dye. All data were subjected to the nonparametric Mann
Whitney Rank Sum Test. The results revealed that Herculite XRV and Heliomolar
paste composites had significantly higher microleakage formation (P < 0.03), and
also they presented higher void formation (P < 0.0001) than Revolution flowable
composite resin.
PMID- 9641098
TI - Microleakage of fissure sealants after occlusal enameloplasty and thermocycling.
AB - This study evaluated the microleakage of a filled and an unfilled sealant after
different occlusal surface treatments. A total of 120 human non carious extracted
molars were cleaned with a water slurry of fine flour of pumice using Crescent
Snap-On pointed brushes in a slow-speed hand piece. The teeth were divided at
random into six groups of 20 teeth each; Group 1 pumice prophylaxis and
PrismaShield filled sealant; Group 2 pumice prophylaxis and Delton opaque
unfilled sealant; Group 3 treatment with a diamond fissure bur (Sorensen Ponta
K.G. 2137 F) and PrismaShield sealant; Group 4 treatment with a diamond fissure
bur (Sorensen Ponta K.G. 2137 F) and Delton opaque sealant; Group 5 treatment
with a 1/4 round carbide bur and PrismaShield sealant; and Group 6 treatment with
a 1/4 round carbide bur and Delton opaque sealant. Before sealant placement, the
enamel occlusal surfaces were acid-etched for 30 seconds using disposable
brushes, rinsed, and dried. The sealants were light-cured for 40 seconds.
Immediately after curing the sealant, 60 teeth were placed in distilled water for
48 hours and 60 teeth were thermocycled (500x, at 5 degrees C - 55 degrees C,
dwell time 30 seconds) and evaluated for microleakage. Wilcoxon and Fisher's
Exact Test revealed no statistical significant difference in microleakage between
the thermocycled and non-thermocycled groups, between the fissure treatment
modalities or between the filled and unfilled sealants.
PMID- 9641099
TI - Fluoride release from three different types of glass ionomer cements after
exposure to NaF solution and APF gel.
AB - The objective of this study was to evaluate the fluoride release from three
different types of glass ionomer cements and the fluoride release after exposure
to NaF solution and APF gel. After determining the fluoride release during 28
days in artificial saliva, specimens were divided into two groups and exposed to
NaF solution and APF gel for 2 min during 20 days. For each material, the release
was highest during the first day, but Kromoglass released statistically
significantly higher amounts of fluoride than the other. Vitrabond and Dyract
followed in order. The differences in all groups were not statistically
significant after third day. For statistical analysis: Paired- T Test, Variance
Analysis and Duncan's Multiple Range Test were used. After exposure to NaF
solution and APF gel all glass ionomer cements were recharged but the specimens
exposed to APF gel were statistically significantly more recharged than NaF
solution. As a result we conclude that glass ionomer cements can act as a
rechargeable slow fluoride release systems and especially in caries active
children, topical NaF applications with glass ionomer cements could be
recommended as a preventive measure. We conclude that these results should be
supported with long term and in vivo studies.
PMID- 9641100
TI - Epidermolysis bullosa: case report of appropriate classification of subtype
because of an early dental exam.
AB - Epidermolysis bullosa is a unique group of disorders that have blister formation
as the common feature. Although there are many variants of this disorder, the
subtypes are classified into three groups based upon the level of tissue
separation that occurs after mechanical trauma is sustained by the skin. Specific
subtypes of EB may have substantial involvement of extracutaneous areas such as
the oral cavity and dentition. This case report demonstrates the importance of a
dental examination at an early age in order to facilitate the correct subtyping
of EB. For the very young patient, correct classification of the subtype of EB
may be very important in identifying the severity of clinical features associated
with the disorder, and with this information the patient and family may become
better aware of potential complications of the disorder such as the dental
defects described in this report.
PMID- 9641101
TI - Congenital absence of parotid glands and lacrimal puncta.
AB - Bilateral parotid aplasia and lacrimal puncta are a rare disorder. A case is
presented in which the clinical diagnosis was confirmed by ultrasonography. The
importance to dentists in early recognition of bilateral parotid aplasia and
lacrimal puncta is emphasized.
PMID- 9641102
TI - Enamel hypoplasia and essential staining of teeth from erythroblastosis fetalis.
AB - The dental, clinical, radiological, pedigree and dermatoglyphic findings of a
patient showing hypoplasia of enamel and intrinsic staining of the teeth from
erythroblastosis fetalis are presented.
PMID- 9641103
TI - Leukemic children: clinical and histopathological gingival lesions.
AB - The relation between leukemia and gingiva was investigated in the present study.
An extensive tumor infiltration in the gingiva was established in 1 of 2 patients
with acute leukemia (AML). An inflammatory cell infiltration in various degrees
was noticed in total 28 patients with leukemia (L). Various degrees of epithelium
hyperplasia in all patients existing in 14 patients with medium intensity and
occurring in 14 patients with light intensity of hyperplasia were observed. An
increase in the keratinization of epithelium, in 3 patients with medium intensity
and 1 patient with light intensity was found. It was also seen that there were
fungal infections in 3 patients with medium intensity, in 6 patients with light
intensity and existing in a total 26 patients with acute lymphoblastic leukemia
(ALL).
PMID- 9641104
TI - Acute lymphoblastic leukemia: dental health of children in maintenance therapy.
AB - The dental health of 41 children aged 4-16 years who were in maintenance therapy
from acute lymphoblastic leukemia (ALL) was examined in relation to the period of
time in maintenance. There was no significant difference in dental experience and
salivary flow rate between the control group and patients with leukemia.
Performed treatment index (PTI) and required treatment index (RTI) scores
reflected that children, who were in maintenance therapy had insufficient dental
care and needed more dental treatments. A statistically significant difference in
salivary pH was found between the children, who were in maintenance therapy for
12-24 months and less than 12 months and also the control group; but the pH
scores of all groups were observed in normal limits.
PMID- 9641105
TI - Dental anomalies caused by oncological treatment: case report.
AB - In infancy, the oncological treatment is at times chemoradiotherapy. This
treatment may cause dental development anomalies that can affect the form and
structure of the tooth. A case report with this type of dental damage is
presented.
PMID- 9641106
TI - Effect of masticatory cycles on apical leakage of obturated teeth.
AB - This study investigated the effect of apical leakage due to masticatory cycles on
root canal treatment. Twenty upper maxillary molars were first obturated using
the warm vertical compaction technique. Four maxillary casts were then built,
with each holding four of the sample molars. The molars were embedded in resin
with the roots separated from the resin by means of a light silicon. The four
remaining teeth served as controls and were not submitted to occlusal forces. A
mechanical device to simulate masticatory cycles subjected the teeth to 0.5 x
10(6) cycles (group A), 10(6) cycles (group B), 2 x 10(6) cycles (group C), and 3
x 10(6) cycles (group D); the control was group E. The roots were placed in 2%
methylene blue dye solution for 72 h and then sectioned longitudinally so that
dye penetration could be measured. The mean values of dye penetration were: 3.70
+/- 0.69 mm, group A; 5.00 +/- 1.14 mm, group B; 6.00 +/- 1.01 mm, group C; 7.23
+/- 0.66 mm, group D; and 2.74 +/- 0.75 mm, group E. The value of dye penetration
increased in correlation with the number of masticatory cycles. This in vitro
study suggests the significant effect of masticatory loads on apical leakage.
PMID- 9641107
TI - Effect of calcium hydroxide on the dissolution of soft tissue on the root canal
wall.
AB - Calcium hydroxide [Ca(OH)2] paste can aid in the cleaning of a root canal because
of its soft tissue-dissolving potential. In this study, we examined with a
scanning electron microscope the dissolution by Ca(OH)2 paste of pulpal tissue
attached to uninstrumented bovine root canal walls. Extracted bovine anterior
teeth were divided into small specimens at the middle portion of the roots. The
experimental groups were treated with sodium hypochlorite (NaOCl), Ca(OH)2, or a
combination of Ca(OH)2 + NaOCl. The control group was given no treatment. The
root canal walls were observed with a scanning electron microscope, and the
amount of remaining pulp tissue was compared. The amount of debris was reduced
remarkably in the groups treated with NaOCl for > 30 s, or Ca(OH)2 for 7 days.
The combination of Ca(OH)2 + NaOCl was more effective than the separate
treatments. The results suggest that Ca(OH)2 as a root canal medicine serves as
an effective agent in removing tissue debris remaining on the root canal walls.
PMID- 9641108
TI - Stimulatory effect of interleukin-6 on plasminogen activator activity from human
dental pulp cells.
AB - The plasminogen activator (PA)-plasmin proteolytic system has recently received
considerable attention because of its participation in a wide variety of
biological activities and in pathological conditions involving tissue
destruction. We examined the effects of interleukin-6 (IL-6) on PA activity and
the gene expressions of tissue type (t) PA and PA inhibitor-1 (PAI-1) in human
dental pulp (HDP) cells. IL-6 treatment induced significantly high PA activity in
the HDP cells in a time- and dose-dependent manner, compared with nontreated
controls. Western-blot analysis showed that tPA protein in the conditioned medium
was stimulated by IL-6, compared with the control. The tPA and PAI-1 mRNA levels
were increased in HDP cells treated with IL-6, as shown by reverse transcriptase
polymerase chain reaction. These results suggest that IL-6 stimulated PA activity
through an enhancement of tPA gene expression and may be involved in
extracellular matrix degradation through the stimulation of the PA-plasmin system
of HDP cells.
PMID- 9641109
TI - Biocompatibility of two apatite cements.
AB - Biocompatibility and osteogenic potential of two calcium phosphate cements (G-5
and G-6) and Super-EBA were investigated by subcutaneous and intraosseous
implantation in 90 rats. Reactions were studied microscopically at 15, 30, and 60
days after implantation. Super-EBA was well tolerated by both soft and hard
tissues. G-5 was highly biocompatible with resorption and bone replacement at
intraosseous implantation sites. G-6 promoted moderate inflammation and a foreign
body giant cell response over the 60-day study period. None of the materials
elicited osteogenesis or dystrophic calcification at the subcutaneous
implantation sites.
PMID- 9641110
TI - Apical sealing ability of glass ionomer sealer with and without smear layer.
AB - The effect of two different root canal cements and removal of the smear layer on
the apical seal in roots obturated with Thermafil obturators was tested. Thirty
extracted human mandibular first molars with 60 canals (mesial roots) were
instrumented with the use of a step-back technique. Teeth were placed into 6
groups of 10 canals each. The first three groups had the smear layer removed with
EDTA and NaOCl, and the other three groups were irrigated with NaOCl only. Canals
were obturated using Thermafil without sealer cement or Thermafil with Ketac-Endo
or Thermafil with zinc oxide-eugenol cement. All roots were placed in India ink
for 4 days. The roots were cleared, and the degree of linear dye penetration was
measured. The study showed that root canal cement significantly improved the
apical seal of the Thermafil obturation technique (p < 0.05), whether the smear
layer was removed or not. The apical seal exhibited by Ketac-Endo was not
significantly different from that provided by zinc oxide-eugenol cement (p >
0.05), regardless of the presence or absence of a smear layer.
PMID- 9641111
TI - Influence of the concentration of ions and foramen diameter on the accuracy of
electronic root canal length measurement--an experimental study.
AB - Investigations on the concentration of cations in human pulp have shown that
pathological changes in the pulp lead to changes in the concentration of ions in
the tissue. Consequently, its electrophysiological characteristics are changed,
which affects the accuracy of electronic root canal length measurements (ERCLMs).
The aim of this study was to examine the effect of concentrations of Na+, K+, and
Ca2+ cations in medium within the canal and around the tooth, and also foramen
diameter, on the accuracy of ERCLMs. The model comprised 21 extracted single
rooted human teeth divided into two experimental groups and one control group,
with seven teeth each. Two aqueous solutions of different concentrations of NaCl,
KCl, and CaCl2 were mixed with agar. The concentrations of Na+, K+, and Ca2+
corresponded to the results of analyses performed by atomic spectrophotometry on
the extirpated human pulps. Agar containing cations was injected into the root
canal prepared with a foramen diameter of 0.25 mm. In the control group, the
teeth were then completely immersed in agar of the same concentration of cations
as the agar inside the canal. In the first experimental group (group 1), the
concentration of ions was higher inside the canal, compared with the
concentration outside the canal. In the second experimental group (group 2), the
order of concentrations was inverse. In all three groups, ERCLMs was performed in
the previously described model. Then, the size of the apical foramens was
enlarged and ERCLMs repeated at foramen diameters of 0.45 mm and 0.70 mm
diameters, respectively. Results indicate that at 0.25 diameters, the most
accurate measurements were taken when the concentrations of ions inside the canal
were higher than outside the canal (Xdif = 1.39 +/- 1.21 mm) (group 1). At
diameters of 0.45 and 0.70 mm, no significant differences were found (p < 0.05)
between the experimental groups (error amounted to Xdif = 6.27 +/- 1.47 mm). In
the control group measurement, error increased with enlargement of the foramen.
PMID- 9641112
TI - Effects of pulsed Nd:YAG laser irradiation on root canal wall dentin with
different laser initiators.
AB - The effects of pulsed Nd:YAG laser irradiation with different laser initiators on
the permeability and ultrastructure of the root canal wall dentin were
investigated in vitro. Forty extracted human single-rooted teeth were randomly
assigned to four groups. Group 1 teeth were not lased as a control. Group 2
specimens received four 10-s duration laser exposures for a total exposure of 40
s/canal. In group 3 specimens, the root canals were painted with black ink and
then lased by the same method as group 2 teeth. In group 4 specimens, root canals
were treated with 38% Ag(NH3)2F and then lased by the same method as group 2
teeth. Laser parameters were set at 2 W, 20 pps. After being placed in 0.6%
rhodamine B solution for 48 h, the teeth were sectioned for study by stereoscope
and scanning electron microscopy. Statistical analysis showed there were
significant differences (p < 0.05) in dentin permeability in the apical areas
between groups 3 and 1, 4 and 1, and 4 and 2. Scanning electron microscopic
examination showed that laser treatment alone had no obvious effects on the root
canal wall. The root canal surfaces prepared for by laser irradiation with black
ink or 38% Ag(NH3)2F revealed melting, smear layer evaporation, and open dentinal
tubules. Black ink was more effective than 38% Ag(NH3)2F as a Nd:YAG laser
initiator.
PMID- 9641113
TI - Black-pigmented bacteria in coronal and apical segments of infected root canals.
AB - Black-pigmented bacteria (BPB) have been associated with infections of endodontic
origin. The purpose of this study was to culture and identify BPB from the apical
and coronal segments of infected root canals to understand better their
ecological relationships. Teeth with a periapical radiolucency were extracted and
immediately placed in reduced transport fluid for transport to an anaerobic
chamber. Of 18 sampled roots, 12 were positive for the growth of BPB. Eight of
the 12 roots with BPB had a carious exposure of the pulp chamber. Seven roots had
Prevotella nigrescens in both the apical and the coronal segments. Six of these
seven teeth had carious exposures of the pulp chamber. Of the 12 roots infected
with BPB, six roots had two different species of BPB, with P. nigrescens always
being one of the species. P. nigrescens was the most often isolated BPB from both
the coronal and apical segments of infected root canals.
PMID- 9641114
TI - In vitro study of a Nd:YAP laser in endodontic retreatment.
AB - Nd:YAP laser is a dental laser with a 1340 nm wavelength. The laser beam is
carried by a 200 to 300 microns fiberoptic and is suitable for endodontic
therapy. We used the Nd:YAP laser in an in vitro experiment to study its
effectiveness in endodontic retreatment. Temperature measurements and irradiation
parameters were first defined. Then Nd:YAP laser irradiation was used, alone or
in combination with hand instruments, to remove various canal sealers and broken
instruments. Clinical parameters were monitored and scanning electron microscopic
observations were conducted. When used at 200 mJ--with a pulse duration of 150
ms, an exposure time of 1 s and a frequency of 10 Hz--Nd:YAP laser preserved the
dentinal walls of the root canal and enabled root canal retreatment without
thermic elevation harming periodontal tissue. It is concluded that, in
combination with hand instruments, the Nd:YAP laser is an effective device for
root canal preparation in endodontic retreatment.
PMID- 9641115
TI - Comparison of the performance of four files with rounded tips during shaping of
simulated root canals.
AB - A total of 160 simulated canals of various angles and positions of curvature were
prepared by hand using either Mani Flexile Files, Mani SEC-O Files, Maillefer
Flexofiles, or Zipperer Flexicut Files. After orifice enlargement, each file type
was used to prepare 40 canals employing a balanced force motion and a modified
double-flared technique. Pre- and postoperative images of the canals were taken
with a videocamera, and stored and manipulated in a computer with image analysis
software. The presence of canal aberrations and the amount of material removed as
a result of preparation were determined from composite images of superimposed pre
and postoperative views. Significant differences (p < 0.001) in preparation time
were observed, with Flexile Files being quickest and SEC-O Files being slowest.
Overall, Flexofiles and Flexicut Files deformed significantly more (p < 0.001)
than Flexile and SEC-O Files. The incidence of canal blockage was not influenced
by instrument type, but the incidence of apical extrusion was significantly
greater (p < 0.001) with SEC-O Files. SEC-O Files created significantly fewer (p
< 0.001) and significantly narrower (p < 0.001) zips, with significantly less (p
< 0.001) removal of material from the outer aspect of the curve and thus
significantly less (p < 0.001) transportation. Flexicut Files created the widest
canals apically, with the greatest removal of material from the outer aspect of
the curve and the most transportation. Flexofiles created significantly more (p <
0.001) perforations. Under the conditions of this study, obvious differences
between instruments were highlighted with SEC-O Files preparing canals more
safely and with least destruction. The unique rounded tip of the SEC-O Files may
have had an influence on the outcome.
PMID- 9641116
TI - The C-shaped mandibular second molar: incidence and other considerations. Members
of the Arizona Endodontic Association.
AB - Although its most common configuration is two roots and three canals, the
mandibular second molar may have many different combinations. Cooke and Cox were
the first to describe a single-rooted mandibular second molar with a continuous
slit connecting some or all of the canals. If sectioned horizontally through the
main portion of the root, this slit had the shape of the letter "C." Other papers
were written and lectures were presented on this and similar entities, but its
frequency and significance have remained the object of speculation because large
numbers of these teeth have not been categorized. By combining the efforts of an
endodontic study club, 811 endodontically treated mandibular second molars were
evaluated. Sixty-two of these (7.6%) were identified as C-shapes. Other aspects
of this configuration were also investigated.
PMID- 9641117
TI - Endodontic therapy in a maxillary second molar with three buccal roots.
AB - In this study, we report a case of a four-rooted maxillary second molar in which
three well-separated buccal roots were located. This case demonstrated that even
though it is not common, an extra root containing an independent root canal may
occur.
PMID- 9641118
TI - Conservative treatment of supernumerary maxillary incisor with dens invaginatus.
AB - A case report is presented describing the treatment of a right maxillary
supernumerary incisor with dens invaginatus. Extensive caries penetration into
the invagination space was subsequently followed by contamination of the included
tissue, but no pulp pathosis has been detected. The purpose of this case report
was to present a treatment modality that enabled the preservation of pulp
vitality by a conservative endodontic approach. Clinical considerations and
treatment are discussed and reported.
PMID- 9641119
TI - Surgical extrusion of a completely intruded permanent incisor.
AB - This report presents a case of a completely intrusive luxation of a mature
permanent central incisor in a 10-yr-old boy. The intruded tooth was repositioned
by using surgical extrusion and stabilization with interdental sutures.
Endodontic treatment was performed with calcium hydroxide paste as the intracanal
medication and a calcium hydroxide-based root canal sealer. This treatment mode
was observed at 18 months and was successful at that time.
PMID- 9641120
TI - Risk assessment of the toxicity of solvents of gutta-percha used in endodontic
retreatment.
AB - Three randomly assigned groups of single-canaled extracted teeth obturated with
gutta-percha were retreated using controlled application of one of three organic
solvents: chloroform, xylene, or halothane. Two additional groups of teeth served
as positive and negative controls. Residual volume of solvent expressed through
the apical foramen during retreatment was determined by the difference of
pretreatment and posttreatment weights of hermetically sealed receptacles
attached to the root surface of the teeth. Results indicate that the amount of
solvent that has been determined to have leached out through the apical foramen
is several orders of magnitude below the permissible toxic dose. Thus, it is
proposed that the use of any of the aforementioned solvents used in the
retreatment of root canals would pose negligible risk to the patient.
PMID- 9641121
TI - Analysis of forces developed during obturations. Wedging effect: Part I.
AB - The aim of this study was to define the "wedging effect" created by the
intracanal forces developed during obturations and to measure it using a force
analyzer device. In endodontics, the wedging effect is the result of, for
example, a plugger pushing gutta-percha into a canal: the plugger functions much
as the rod of a hydraulic jack and the vertical force applied by this rod induces
in the cylinder (i.e. the canal) a hydrostatic pressure that is relatively equal
in all directions. It is these forces resulting from the hydrostatic pressure
that have been labeled the wedging effect. The original device, the Endographe,
had a monobloc cupule for measuring the external vertical and horizontal forces
developed by a practitioner, but it was unable to measure the intracanal forces.
With a new cupule composed of two independent parts joined under pressure, the
wedging effect was recorded and analyzed. Two obturation methods, warm vertical
compaction and lateral condensation, were performed by endodontists. The forces
were depicted by Endogrammes as a function of time. For all of the forces
developed during the two techniques, the mean values showed a nonsignificant
difference between the different practitioners. The use of graphs provides a new
approach to the analysis of intracanal forces as they develop our time and
permits the comparison of different obturation techniques.
PMID- 9641122
TI - Analysis of forces developed during obturations. Wedging effect: Part II.
AB - The aim of this study was to use a force analyzer device, the modified Endographe
with a new cupule, to compare the forces and wedging effects developed in the
root canal using four obturation techniques: warm vertical compaction, lateral
condensation, thermomechanical compaction, and Thermafil condensation. The
different methods--that varied in instrumentation, duration, and compaction load-
were studied from graphs representing the force application sequences. In
addition, the graphs resulting from modifications in technique (such as using an
undersized spreader and pluggers that were either too small or too big) and
deliberately induced failures in technique (by use of a too small condenser or a
too small master cone) were studied. The mean values for the wedging effect for
warm vertical compaction, lateral condensation, thermomechanical compaction, and
Thermafil condensation were, respectively, 0.65 +/- 0.07 kg, 0.8 +/- 0.1 kg, 0.6
+/- 0.08 kg, and 0.03 +/- 0.01 kg. The use of graphs provides a new approach to
the analysis of obturation techniques.
PMID- 9641123
TI - The effect of the bleaching agent sodium perborate on macrophage adhesion in
vitro: implications in external cervical root resorption.
AB - The purpose of this study was to investigate the in vitro effect of sodium
perborate, which is used as a bleaching agent in the treatment of discolored
pulpless teeth, on substrate adherence capacity of macrophages. Inflammatory
macrophages were obtained from Wistar rats and resuspended in RPMI-1640 medium.
As a test of macrophage adhesion, the adherence capacity of macrophages to a
plastic surface was determined. Assays were conducted in Eppendorf tubes for 15
min of incubation at 37 degrees C in a humidified atmosphere of 5% CO2. The
adherence index was calculated. Results showed that sodium perborate decreased in
a dose-dependent manner and decreased significantly (p < 0.05) the adherence
index of rat peritoneal macrophages. Sodium perborate was less potent than sodium
hypochlorite and eugenol in inhibiting macrophage adhesion. The inhibitory effect
of sodium perborate on macrophage adhesion further supports the concept that this
agent is not implicated in external cervical root resorption associated with
intracoronal bleaching.
PMID- 9641124
TI - Development of an anaerobic bacterial leakage model.
AB - The majority of bacteria associated with infections of endodontic origin are
strict anaerobes. The purpose of this study was to develop an endodontic
microleakage model using strict anaerobic bacteria in a two-chamber system. Nine
species of anaerobic bacteria were tested for viability and detection by either
turbidity or color change of the broth. A survey of pH chromogenic substrates
revealed that bromcresol purple (pH 5.2 = yellow, pH 6.8 = purple) could be used
as a chromogenic indicator to detect the growth of anaerobic bacteria. Peptone
yeast extract-glucose broth (PYG) and brain heart infusion broth (BHI) were each
used alone and with bromcresol purple (bpPYG, bpBHI) in this study. Fusobacterium
nucleatum and F. necrophorum were viable in all four media for > 2 wk and
produced both turbidity and a color change after only 1 day of incubation.
Veillonella parvula in either bpBHI or BHI and Peptostreptococcus anaerobius in
either bpPYG or BHI were viable for > 2 wk and showed a color change or turbidity
after 1 or 2 days. The results indicate that leakage of strict anaerobes may be
evaluated in a two-chamber system.
PMID- 9641125
TI - pH measurement of root canal sealers.
AB - The purpose of this study was to compare the surface pH level of three different
type sealers after mixing at various time intervals in vitro. The cements were
mixed according to the manufacturer's instructions. They were incubated to set in
100% humidity at 37 degrees C for 1 h, 24 h, 5 days, 8 days, 2 wk, 3 wk, 4 wk, 5
wk, and 7 wk. pH was calculated by a Twin pH meter. The pH levels of the three
sealers were different at various time intervals (p < 0.0001). The resin-based
cement had a acid pH level (pH < 7.0). The calcium hydroxide-based cement showed
a higher alkalinity pH level (pH > 7.0). The zinc oxide-eugenol-based cement
showed a similar pH level to the calcium hydroxide cement at the end of the
measurement. We postulated that, in endodontic therapy when those healing is
needed, the alkaline-based sealer is the choice.
PMID- 9641126
TI - The effect of 4% titanium tetrafluoride solution on root canal walls--a
preliminary investigation.
AB - The aim of the present study was to evaluate the effect of 4% titanium
tetrafluoride (TiF4) solution on root canal walls by scanning electron
microscopy. Twenty four root canals with or without a smear layer were treated
with 4% TiF4 solution. Scanning electron microscopic observation of the smeared
canal walls showed that TiF4 solution modified the smear layer and produced a
massive structure. In smear-free group, a granular coating was formed on
intertubular and intratubular dentin. The stability of this layer was tested
further with EDTA and/or NaOCl irrigations on 20 additional specimens. It was
observed that none of the solutions was able to remove this modified smear layer.
These results may indicate that this extremely stable structure may be
advantageous in endodontics, because it can prevent further infection of root
canal dentin by sealing off the tubules permanently, and can reduce microleakage
by preventing further dissolution and disintegration of the smear layer.
PMID- 9641127
TI - Physical properties of CH61, a newly developed root canal sealer.
AB - This study was performed to evaluate the physical properties (sealing, flow,
radio-opacity, working time, and solubility) of a newly developed root canal
sealer, CH61. It was compared with Canals, Sealapex, and AH26, which are typical
commercially available root canal sealers. The sealing ability was evaluated by
dye penetration. The flow was evaluated by two methods. One was flow in the
vertical dimension, and the other was disk diameter. Radio-opacity, working time,
and solubility were performed in accordance with the standards of the
International Organization for Standardization. No dye penetration after
immersion for 24 h was noted. In CH61, and there were significant differences
between the values for CH61 and Canals, Sealapex, or AH26 (p < 0.001). For flow,
the results differed from method to method. The radio-opacity decreased in the
following order: AH26, Canals, CH61, and Sealapex. The solubility was the lowest
for CH61. This study showed that CH61 had excellent sealing properties and low
solubility.
PMID- 9641128
TI - The CO2 laser as an aid in direct pulp capping.
AB - Two hundred direct pulp capping procedures were conducted in the present study.
One hundred of them were performed with the CO2 laser, and 100 were conducted
conventionally as a control by using a calcium hydroxide preparation. Follow-up
examinations were performed after 1 wk and monthly for 12 months after treatment.
Thermal tests were used for vitality assessments and laser Doppler flowmetry for
direct measurement of pulpal blood. In the group of pulps treated with the CO2
laser, the last recall examination at 12 months demonstrated that 89 teeth
remained vital, corresponding to a success rate of 89%. In the control group, the
success rate was considerably lower (68%). Exposure sizes and mean patient age
were nearly identical in both groups. The CO2 laser seems to be a valuable aid in
direct pulp capping.
PMID- 9641129
TI - Stimulation of interleukin-6 production in human dental pulp cells by
peptidoglycans from Lactobacillus casei.
AB - Interleukin-6 (IL-6), which is a multifunctional cytokine, has an important role
in acute and chronic inflammation. The peptidoglycan (PG) was purified from
Lactobacillus casei, which was a Gram-positive bacteria frequently isolated from
deep carious lesions and suspected to be a pathogen of pulpitis. In this study,
the effects of PG on the production of IL-6 in human dental pulp cells were
examined. PG stimulated IL-6 production in a time- and dose-dependent manner.
Reverse transcriptase-polymerase chain reaction experiments showed that the
increase was dependent on the enhancement of IL-6 mRNA levels. These findings
suggest that Gram-positive bacteria, such as L. casei, from carious lesions,
might be involved in developing pulpitis through the stimulation of IL-6
production.
PMID- 9641130
TI - Strengthening immature teeth during and after apexification.
AB - The purpose of this study was to evaluate the strengthening effect of an internal
resin bonding technique. One hundred central incisors were endodontically treated
and divided equally into five groups. Group 1, without any cervical preparation
and with access repaired with bonded resin, served as the positive control. Teeth
in groups 2 to 5 were cervically prepared to simulate the thin dentinal wall of
immature teeth, and obturation material was removed to 3 mm below the
cementoenamel junction (CEJ). In group 2, the negative control, the access was
restored with bonded composite to the level of the CEJ. In group 3, access was
restored with composite resin 3 mm apical to the CEJ using a clear post system.
Group 4 was treated similarly to group 3, but an opaque post replaced the clear
post. Group 5 was treated like group 3, after which a metal post was cemented
into the channel left after removal of the clear post. All teeth were subjected
to compression testing and the force required to fracture the teeth cervically
was recorded for each group and the Kruskal-Wallis analysis performed to detect
intergroup differences. All of the bonded resin techniques significantly
strengthened the teeth against fracture, compared with the negative control group
(p < 0.05). None of the experimental groups (3-5) were significantly different
from the positive control group.
PMID- 9641131
TI - Surgical endodontics of upper molars: relation to the maxillary sinus and
operation in acute state of infection.
AB - Findings in 200 cases of root resection of first maxillary molars showed
perforation to the sinus in half of the cases. In 42% of the cases, the first
maxillary molar had root resection performed in a subacute or acute state of
infection. Only two cases developed postoperative sinusitis. Antibiotic treatment
was indicated preoperatively in 3% and postoperatively in 5%. Postoperative
symptoms, such as pain and swelling, were usually moderate, possibly because of a
nontraumatizing operation technique, a careful removal of infected tissue, and a
good drainage by loose suturing.
PMID- 9641132
TI - Interpretation of periapical lesions comparing conventional, direct digital, and
telephonically transmitted radiographic images.
AB - The purpose of this study was to evaluate direct digital radiography (DDR) and
telephonically transmitted images versus conventional radiography in the
interpretation of artificial periapical bone lesions. Five teeth were chosen from
four cadaver jaw specimens. Three types of DDR images were evaluated: DDR stored
images, DDR transmitted images, and DDR reversed images. A total of 150 DDR
computer monitor images and 56 D-speed film images were evaluated by three
endodontists and one endodontic graduate student. The Wilcoxon signed-ranks test
was used for statistical analyses of the results. DDR reversed images were
statistically inferior to DDR stored images, DDR transmitted images, and
conventional radiography images (p < 0.0001). There were no statistically
significant differences between DDR stored images, DDR transmitted images, and
conventional film images in the ability of the evaluator to identify artificial
periapical bone lesions (p > 0.05).
PMID- 9641133
TI - Metastatic carcinoma to the mandible that mimicked pulpal/periodontal disease.
AB - An oral cavity metastasis from a poorly differentiated carcinoma, presumed to
have originated in the pancreas, mimicked a dental abscess. An additional
metastasis to the lung caused a postobstructive lobar pneumonia that masked the
lesion, thereby delaying the diagnosis of malignancy. This case report
illustrates how the clinical manifestations of a widely disseminated neoplasm led
to initial medical confusion and subsequent dental misdiagnosis, and serves to
caution of a possible pitfall in the dental evaluation of endodontic lesions.
PMID- 9641134
TI - American Association of Endodontists' 55th Annual Session. New York, May 6-10,
1998. Abstract.
PMID- 9641135
TI - Scanning electron microscopic study of dentin lased with argon, CO2, and Nd:YAG
laser.
AB - The purpose of this study was to compare morphological changes on the dentin
surface induced by laser light delivered perpendicular or parallel to the dentin
surface. The surface of the dentin slices and the root canal walls were lased
with argon, CO2, and Nd:YAG lasers. When the laser beam was parallel to the
dentin, the effects of the laser energy ranged from no effect to eroding and
melting of the smear layer and dentin in the samples. When the laser beam was
perpendicular to the surface, all three lasers produced well-shaped craters. From
this, it was concluded that the angle of the laser beam in relation to the target
surface can be a deciding factor of how much energy will be absorbed by the
dentin and consequently of the morphological changes induced by the laser.
PMID- 9641136
TI - In vivo comparison of the biocompatibility of two root canal sealers implanted
into the subcutaneous connective tissue of rats.
AB - The purpose of this study was to evaluate the in vivo biocompatibility of Apexit
(a calcium hydroxide) and Pulp Canal Sealer (a classic zinc oxide-eugenol), root
canal sealers, after implantation in rat connective tissue. Forty-four white
female Wistar-Furth rats were used. Each sealer was placed in Teflon tubes and
implanted into specific dorsal subdermal tissues sites. Implants were removed
after 5, 15, 60, and 120 days; fixed; and histologically prepared for
microscopical evaluation. Severe inflammatory reactions with differing extensions
of necrosis were observed with Apexit on the 5th and 15th days. The intensity of
the reaction had diminished by the 60th day, and this reduction continued
progressively through the 120th day. It was characterized by the presence of
connective tissue with a few macrophages. Moderate to severe inflammation with
confined areas of necrosis was observed in the Pulp Canal Sealer specimens on the
5th day. The intensity of the reaction diminished by the 15th, 60th, and 120th
days, but remained slightly greater than Apexit through longterm observation
periods.
PMID- 9641137
TI - Endodontic pathogens stimulate monocyte chemoattractant protein-1 and interleukin
8 in mononuclear cells.
AB - Microbial infection of the dental pulp leads to the recruitment of leukocytes and
the formation of lesions of endodontic origin. The chemokines interleukin-8 (IL
8) and monocyte chemoattractant protein-1 (MCP-1) are relatively specific
chemoattractants for neutrophils and monocytes, respectively. In the present
studies, peripheral blood mononuclear cells were stimulated by Streptococcus
mutants, Porphyromonas endodontalis, and Peptostreptococcus anaerobius, which are
associated with lesions of endodontic origin. Each of these bacteria induced a
dose-dependent increase in IL-8 and MCP-1, determined by ELISA. The levels
induced are physiologically relevant. However, low doses of P. endodontalis were
less effective in inducing IL-8 or MCP-1 expression, compared with S. mutants or
P. anaerobius. Thus, these bacteria can induce significant levels of the
chemokines IL-8 and MCP-1, which could contribute to the recruitment of
neutrophils or monocytes in vivo. The expression of these mediators may
contribute to the development of endodontic infections, particularly with regard
to inflammatory leukocyte recruitment.
PMID- 9641139
TI - Cutting efficiency of a mid-infrared laser on human enamel.
AB - In this study, the cutting ability of a newly developed dental laser was compared
with a dental high-speed handpiece and rotary bur for removal of enamel.
Measurements of the volume of tissue removed, energy emitted, and time of
exposure were used to quantify the ablation rate (rate of tissue removal) for
each test group and compared. Cutting efficiency (mm3/s) of the laser was
calculated based on the mean volume of tissue removed per pulse (mm3/pulse) and
unit energy expended (mm3/J) over the range of applied powers (2, 4, 6, and 8 W).
The specimens were then examined by light microscopy and scanning electron
micrographs for qualitative analysis of the amount of remaining debris and the
presence of the smear layer on the prepared enamel surface. Calculations of the
cutting efficiency of the laser over the range of powers tested revealed a linear
relationship with the level of applied power. The maximum average rate of tissue
removal by the laser was 0.256 mm3/s at 8 W, compared with 0.945 mm3/s by the
dental handpiece. Light microscopy and scanning electron micrograph examinations
revealed a reduction in the amount of remaining debris and smear layer in the
laser-prepared enamel surfaces, compared with the conventional method. Based on
the results of this study, the cutting efficiency of the high-speed handpiece and
dental bur was 3.7 times greater than the laser over the range of powers tested,
but the laser appeared to create a cleaner enamel surface with minimal thermal
damage. Further modifications of the laser system are suggested for improvement
of laser cutting efficiency.
PMID- 9641138
TI - Cytotoxicity of endodontic materials.
AB - An in vitro cell culture model of human gingival fibroblasts and L-929 cells was
used to measure the cytotoxicity of currently used root canal sealers Endomet,
CRCS, and AH26 and root-end filling materials Amalgam, Gallium GF2, Ketac Silver,
mineral trioxide aggregate (MTA), and Super-EBA. Cytotoxic effects were assessed
using the MTT assay for mitochondrial enzyme activity and the CV assay for cell
numbers. Using inserts culture and L-929 fibroblasts. All-Bond-2 was also
evaluated. The statistical analysis of results showed that CRCS was the least
cytotoxic sealer followed by Endomet and AH26. Among root-end filling materials,
MTA was not cytotoxic; Gallium GF2 displayed little cytotoxicity; and Ketac
Silver, Super-EBA, and Amalgam showed higher levels of cytotoxicity. All Bond-2
also displayed a high degree of cytotoxicity. CRCS was the best root canal sealer
and MTA the best root-end filling material. The outcome was favorable also for
Gallium GF2 as a retrofilling material.
PMID- 9641140
TI - A comparison of amounts of apically extruded debris using handpiece-driven nickel
titanium instrument systems.
AB - One hundred single-rooted teeth were instrumented with Lightspeed, Profile .04
Taper Series 29, and NT McXIM instruments according to the recommendations of the
manufacturers, and Flex-R files using the balanced force technique. Groups were
comparable with respect to average curvature, canal length, and major and minor
foramen size. A standard amount of irrigant was used for each tooth. Apically
extruded debris and irrigant were collected and weighed. Debris was desiccated
before being weighed. There were no statistically significant differences among
the four groups with respect to total extruded debris. The amount of extruded
debris was positively correlated with the amount of irrigant extruded. Factors
such as canal length, curvature, and foramen size did not affect the amount of
debris extruded.
PMID- 9641141
TI - Analysis of stress distribution in a maxillary central incisor subjected to
various post and core applications.
AB - In this study, stress distribution in a maxillary central incisor that was
subjected to endodontic treatment and various post and core applications was
determined by using a three-dimensional finite-element method. Cast gold post and
gold core and different combinations of prefabricated stainless steel post, or a
prefabricated titanium post with amalgam or composite cores were considered. In
all cases, the tooth was assumed to have a porcelain crown. The primary purpose
of the study was to evaluate the stress distribution due to simulated biting
forces and thus investigate the reliability of different post and core
applications. It was found that, within the limitations of the study, the cast
gold post and gold core application yielded the best result. The second purpose
of the study was to highlight the importance of using a unique stress value,
which contains the effects of all the possible stress components existing upon
loading in the determination of a possible failure. A resultant stress value and
all the constituent components were shown in detail, and it was proved that an
estimation independently based on an individual component might lead to erroneous
results.
PMID- 9641142
TI - In vitro adhesion of two strains of Prevotella nigrescens to the dentin of the
root canal: the part played by different irrigation solutions.
AB - Blocks of bovine incisor dentin, on the root canal surface of which a smear layer
had been formed, were inoculated in vitro with two strains of Prevotella
nigrescens, a wild sampled strain and a reference one (NCTC 9336). Half the
blocks were pretreated with irrigating solutions: 6% citric acid for 5 min +
6.25% sodium hypochlorite for 10 min. They were compared with the other blocks
simply rinsed in distilled water (i.e. the control samples). The bacteria
adhering to the dentin surface after an incubation time of 3 h were counted by
direct examination using a scanning electron microscope. The adhesion of P.
nigrescens was less marked on all of the samples treated with irrigating
solutions. Adherence was particularly significant in the case of the wild strain
(F = 10.22). The latter was far more active than the reference strain (F =
35.82). The use of a chelating agent at the end of root canal preparation served
to remove the smear layer and limited the attachment of P. nigrescens to the
dentin.
PMID- 9641143
TI - Balance of interleukin-1 beta and interleukin-1 receptor antagonist in human
periapical lesions.
AB - Interleukin-1 beta (IL-1 beta) has been considered as a major potent mediator of
bone resorption and implicated in the development of human periapical lesions.
Among naturally occurring interleukin-1 (IL-1) inhibitors, IL-1 receptor
antagonist (IL-1ra) is a 22 kDa protein that shares homology with IL-1 beta and
IL-1 alpha, binds to IL-1 receptor with similar affinity to IL-1, and has no
known agonist properties. In this study, we measured the periapical exudate (PE)
levels of IL-1 beta and IL-1ra from human periapical lesions. PE samples were
collected from root canals during routine endodontic treatments, and the enzyme
linked immunosorbent assay was used to measure PE-IL-1 beta and IL-1ra.
Detectable levels of both IL-1 beta and IL-1ra were found in 25 of 29 clinical
samples. Relatively high levels of IL-1ra compared with IL-1 beta (mean IL-1ra:IL
1 beta ratio = 128:7; range: 0.9 to 495.4), and significantly positive
correlation between IL-1ra and IL-1 beta levels was found. The PE-IL-1ra:IL-1
beta ratios obtained from symptomatic lesions were significantly lower than those
from asymptomatic lesions. These results suggest that IL-1ra-mediated IL-1
antagonism occurred to block locally produced IL-1 activity, and the balance of
IL-1 to IL-1ra production may be crucial in the development of periapical
lesions.
PMID- 9641144
TI - In vitro evaluation of the reliability of the Endex electronic apex locator.
AB - A new generation of electronic apex locators (Endex) that operates in moistened
canals has been developed lately. An experimental comparison of this apparatus
with the real, tactile, and radiographic measurements of the root canal length
has been conducted. Results show that tactile determination is highly inaccurate
and that the Endex is as accurate as radiographic measurements. It also
demonstrates that the nonreproducibility of radiographic measurements is
statistically significant, whereas that of the Endex is not significant.
PMID- 9641145
TI - The effect of instrument precurving on transportation in simulated curved canals.
AB - The results of instrumentation studies in small curved canals using various
instruments and techniques are not consistent. The amount of instrument
precurving and a gradual or abrupt curve of the canal may have influenced the
results of these studies. One hundred sixty resin blocks with simulated canals
were used. Eighty blocks had gradual (GC) 30 degree curves, the remainder had
abrupt (AC) 30 degree curves. Ten blocks for each curvature and for each degree
of precurving amount (0, 15, 20, 25, 30, 35, 40, or 45 degrees) were instrumented
with a machine that imparted only an in and out motion. The simulated canals were
size 30 at the apex, and size 30 stainless steel K-files were used to instrument
the canals. A transportation ("t") index was determined at two levels: T1 (1 mm
from the apex) and TB (a line bisecting the curve of the canal). For GC at T1 and
TB, 40- and 20-degree curved instruments respectively produced significantly less
transportation than all other curvatures (p < 0.0001). For AC at T1 and TB, 35
and 25 degree instruments respectively produced significantly less transportation
than all other curvatures (p < 0.0001). Comparing GC and AC, the transportation
for AC was significantly less (p < 0.0015).
PMID- 9641146
TI - A study of the dental pulp cavity of mandibular first permanent molars in the
Kuwaiti population.
AB - This study documented the complexity of the root canal system in the mandibular
first permanent molar. Forty-nine plastic replicas were used from mandibular
first permanent molars obtained from young Kuwaitis. Results revealed that the
tooth had 2 canals, 3 canals, and 4 canals 6.1%, 67.4%, and 26.5% of the time,
respectively. The number, distribution, and apical exit of the canals were
compared with the results of previous related reports. Several recommendations
were given to aid in the diagnosis and treatment of extra root canals.
PMID- 9641147
TI - Shaping ability of Mity Roto 360 degrees and Naviflex rotary nickel-titanium
instruments in simulated root canals. Part 1.
AB - The aim of this study was to determine the shaping ability of Mity Roto 360
degrees and Naviflex nickel-titanium rotary instruments in simulated root canals.
In all, 80 canals consisting of four different shapes in terms of angle and
position of curvature were prepared by Mity Roto 360 degrees and Naviflex
instruments using the techniques recommended by the manufacturers. This study
describes the efficacy of the instruments in terms of preparation time,
instrument failure, canal blockages, change in canal length, and three
dimensional canal form. Overall, the mean preparation time for canals prepared
using Mity instruments was 5.99 min and 5.81 min when using Naviflex instruments.
Canal shape had no significant effect on the speed of preparation with either
instrument. No instruments separated during the study; however, 14 Naviflex and 2
Mity instruments were deformed. Canal type did not influence significantly the
tendency of either instrument to deform. None of the canals became blocked with
debris during preparation. The majority of canals prepared by both instruments
retained their original working length, and there was no significant difference
between the canal shapes in terms of the mean loss of distance or category of
distance change for either instrument. Apical stops as judged from intracanal
impressions were present in 29 (72%) of the canals prepared with Mity instruments
and in 33 (82%) of those prepared with Naviflex instruments. However, the
majority were judged to be of poor quality. Significant differences (p < 0.05)
were noted in the quality of apical stops between the canal types using Mity
instruments. Canals prepared with Mity and Naviflex instruments were found to be
smooth in the apical half of the canal in approximately one-half of the specimens
and coronally in nearly all canals. Neither instrument produced horizontal or
longitudinal grooves. Favorable flow characteristics were apparent in over one
half of the canals prepared with Mity Roto instruments; however, nearly all
specimens had poor taper. Flow and taper were generally poor in the specimens
prepared with Naviflex instruments. Under the conditions of this study, Mity Roto
360 degrees and Naviflex instruments prepared canals rapidly, with no
separations, canal blockages, and with minimal change in working length.
Although, flow was adequate using Mity Roto 360 degrees instruments, the taper
characteristics were less than ideal compromising the three-dimensional form of
the canals. Naviflex instruments, while creating better taper, produced poorer
flow characteristics. The results suggest that when using Mity Roto 360 degrees
or Naviflex instruments, the stepdown sequence should be modified to improve
canal flow and taper. Alternatively, an instrument with increased taper should be
used to complete preparation before obturation.
PMID- 9641148
TI - Shaping ability of Mity Roto 360 degrees and Naviflex rotary nickel-titanium
instruments in simulated root canals. Part 2.
AB - The aim of this study was to determine the shaping ability of Mity Roto 360
degrees and Naviflex rotary nickel-titanium instruments in simulated canals.
Forty simulated root canals made up of four different shapes in terms of angle
and position of curvature were prepared by both sets of instruments using a
stepdown approach. This study describes the efficacy of the instruments in terms
of prevalence of canal aberrations, the amount and direction of canal
transportation, and thus the overall postoperative shape. Pre- and postoperative
images of the canals were taken using a videocamera attached to a computer with
image analysis software. The pre- and postoperative views were superimposed to
highlight the amount and position of material removed during preparation. Neither
Mity Roto 360 degrees nor Naviflex instruments created any zips or elbows. Ledges
were produced in 20 (50%) canals prepared with Mity instruments and in 29 (72%)
canals prepared with Naviflex instruments. Statistically significant differences
(p < 0.001) between canal shapes occurred in relation to the incidence of ledges
with 40 degrees canals (35) associated with more aberrations than 20 degrees
canals (14); the position of the beginning of the curve had no effect. The
distance of ledges from the end point of preparation was also affected
significantly (p < 0.01) by canal shape. Neither instrument created any
perforations or danger zones. At specific positions along the canal length, canal
shape had a significant influence on total width and the amount of material
removed from the inner and outer aspects of the canal curve. The direction of
canal transportation at the end point of preparation was most frequently toward
the outer aspect of the curve in canals prepared with Naviflex instruments,
whereas the Mity instruments produced a more balanced preparation. At the apex
and beginning of the curve, transportation with both instruments was generally
toward the outer aspect of the curve. Overall, mean absolute transportation was
small and was below 0.1 mm at every position except the orifice. Under the
conditions of this study, Mity Roto 360 degrees and Naviflex rotary instruments
prepared canals with a high incidence of ledges. However, in the absence of other
aberrations, both instruments would seem to be a valuable addition to the
endodontic armamentarium.
PMID- 9641149
TI - Herpes zoster infection as a differential diagnosis of acute pulpitis.
AB - Many diseases can cause orofacial pain, and the diagnosis must be established
before final treatment. This case report presents a patient with orofacial pain
that was diagnosed as an acute pulpitis. However, there was no evidence of this
problem on examination. After 4 days, the patient showed multiples vesicles on
the face, and a herpes zoster viral infection was diagnosed. The patient was
treated with acyclovir and, after 2 yr, she still complains of facial
sensitivity.
PMID- 9641150
TI - Osseointegration treatment of transverse root fractures in the region of the
alveolar crest.
AB - A method of using osseointegrated implants as an alternative treatment modality
for transverse root fractures near the osseous crest is presented. A 15-mm
Branemark implant was placed immediately after extraction of a maxillary central
incisor with transverse root fracture. Five months after stage I surgery, the
implant was uncovered. Custom fabrication of a substructure core cast directly to
the titanium single tooth abutment was necessary due to the palatal inclination
of the fixture. An overcasting porcelain fused to gold crown was fabricated to
avoid an unesthetic labial access for the abutment screw. This treatment
indicates that the use of osseointegrated implants seems to provide an effective
solution to replacing teeth with transverse root fractures.
PMID- 9641151
TI - Identification of a gene for nephronophthisis.
PMID- 9641152
TI - Autosomal dominant hypertension with brachydactyly: an enigmatic form of
monogenic hypertension.
PMID- 9641153
TI - Cell growth and cell death in renal distal tubules, associated with diuretic
treatment.
PMID- 9641154
TI - Oxidative stress as the triggering event for vascular remodelling.
PMID- 9641155
TI - Goodpasture syndrome and end-stage renal failure--to transplant or not to
transplant?
PMID- 9641156
TI - Why are mutations in COL4A5 not detectable in all patients with Alport's
syndrome?
PMID- 9641157
TI - Glomerular involvement in Behcet's disease.
PMID- 9641158
TI - Microdomain structure of polymeric surfaces--potential for improving blood
treatment procedures.
PMID- 9641159
TI - Does pre-operative duplex examination improve patency rates of Brescia-Cimino
fistulas?
PMID- 9641160
TI - Continuous renal replacement therapies in sepsis: where are the data?
PMID- 9641161
TI - Honesty in publication.
PMID- 9641162
TI - Podocytes and the development of segmental glomerulosclerosis.
PMID- 9641163
TI - Skin cancers in transplant patients.
PMID- 9641164
TI - Laudatio for Professor Mary G. McGeown.
PMID- 9641165
TI - Primary and secondary uraemic hyperparathyroidism: from initial clinical
observations to recent findings.
PMID- 9641166
TI - Molly McGeown and renal transplantation.
PMID- 9641167
TI - Cytokine regulation of low-density lipoprotein receptor gene transcription in
human mesangial cells.
AB - BACKGROUND: The intracellular transport of lipids through regulation of the LDL
receptor (LDLr) may be important in the progression of renal dysfunction. The
present study was undertaken to investigate whether cytokines have any major
effects on LDLr regulation and lipid-mediated glomerular injury in human
mesangial cells (HMC). METHODS: We explored the effects of 50 ng/ml of tumour
necrosis factor alpha (TNF alpha), 5 ng/ml of transforming growth factor beta
(TGF beta), platelet-derived growth factor (PDGF), and interleukin-1beta (IL
1beta) on the regulation of LDLr gene transcription in a human mesangial cell
line (HMCL) using cell proliferation, LDL binding, northern blot and LDLr
promoter activity assays. RESULTS: TNF alpha, TGF beta, PDGF or IL-1beta did not
significantly stimulate HMCL proliferation at the concentrations given above, but
maximally stimulated LDLr mRNA expression and increased LDLr promoter activity by
167.48+/-23.56%, 150.47+/-24.41%, 127.71+/-24.65% and 163.01+/-31.91%
respectively, at 24 h. An increased LDL binding was observed in parallel with
increased LDLr mRNA. The tyrosine kinase transduction pathway was involved in
LDLr upregulation induced by all four cytokines. Additionally, TGF beta involved
serine/threonine kinase and G-protein pathways, and IL-1beta involved calmodulin,
serine/threonine kinase and PKC pathways in upregulating LDLr. A high
concentration of LDL (250 microg/ml) inhibited promoter activity, but TNF alpha,
TGF beta, PDGF and IL-1beta co-incubated with LDL could override transcriptional
inhibition by LDL. CONCLUSION: TNF alpha, TGF beta, PDGF and IL-1beta increased
LDLr gene expression by increasing sterol-independent and mitogenesis-independent
gene transcription. This process may contribute to lipid deposition and foam cell
formation in HMC.
PMID- 9641168
TI - Differentiating and proliferative effects of HGF in renal proximal tubular cells
are mediated via different signalling pathways.
AB - BACKGROUND: As a renotropic cytokine, hepatocyte growth factor (HGF) prevents
acute renal failure and accelerates renal regeneration. HGF initiates its
biological effects by interaction with specific transmembrane receptors, the c
Met proto-oncogene, possessing an intracellular tyrosine kinase domain. We tested
the hypothesis of whether the complex biological effects of HGF in renal proximal
tubular cells are mediated by different intracellular signalling cascades and/or
different receptors. METHODS: PT-1 cells, a proximal tubular cell line derived
from rabbit kidney, were cultured under defined serum-free conditions to examine
the biological effects of exogenously added HGF. By specific assays, we
determined HGF binding and its effects on cell proliferation, migration,
scattering and tubulogenic differentiation. To investigate whether HGF action
could be inhibited by protein tyrosine kinase inhibitors (PTKIs), cells were
incubated with HGF and different concentrations of herbimycin A, genestein,
methyl-2,5-dihydroxycinnamate (MDC) and geldanamycin. All PTKIs are known
inhibitors of pp60(c-src), a non-receptor tyrosine kinase involved in cell growth
control. RESULTS: HGF bound with high affinity to cell membrane receptors and
displayed multiple biological effects. Compared with serum-free controls, HGF
increased the number of microvilli 1.5-fold, enhanced cell proliferation and
migration 1.8-fold, and stimulated the formation of tubular structures 2.3-fold.
Consistent with the known tyrosine kinase activity of the c-Met receptor, the
mitogenic and motogenic effects of HGF were inhibited by PTKIs in a dose
dependent manner with the following order of potency: geldanamycin > herbimycin A
> genestein > MDC. In contrast, however, the HGF-induced tubulogenic cell
differentiation was not inhibited specifically by PTKIs. CONCLUSIONS: The finding
that PTKIs inhibited the mitogenic response but not the tubulogenic
differentiation induced by HGF indicates different intracellular signal
transduction pathways. We suggest that pp60(c-src) plays a key role in mediating
the mitogenic and motogenic action of HGF, whereas tubulogenic cell
differentiation induced by HGF is transduced by a pp60(c-src)-independent
signalling pathway.
PMID- 9641169
TI - Comparative study of cyclosporin A, cyclosporin G, and the novel cyclosporin
derivative IMM 125 in isolated glomeruli and cultured rat mesangial cells: a
morphometric analysis.
AB - BACKGROUND: One adverse side-effect of the immunosuppressive drug cyclosporin A
(CsA) is a decrease in glomerular filtration rate (GFR). This effect might be the
result of increased glomerular contractions. The present study compared the
contractile effects of CsA, cyclosporin G (CsG) and the novel cyclosporin
derivative IMM 125 in isolated rat glomeruli and primary cultures of rat
mesangial cells. METHODS: Interactive image analysis was used to measure
glomerular and mesangial cell contraction. RESULTS: CsA, CsG, and IMM 125 at
concentrations of 0, 10(-9), 10(-8), 10(-7), 10(-6) and 10(-5) M caused a time
dependent and a concentration-dependent contraction of isolated glomeruli and
mesangial cells 30 min after incubation. In glomeruli, CsA was more potent than
CsG and IMM 125. In mesangial cells, IMM 125 also exhibited the lowest
contractile activity, while CsA and CsG were almost equally myoreactive. The
absolute degree of the glomerular contraction was proportional to the number of
contracting mesangial cells in one glomeruli. The number of responding cells
after incubation with IMM 125 and CsG were lower compared to CsA, which might
explain the different response with CsG and CsA in both models. CONCLUSIONS:
Since the concentrations used in these experiments were close to that reached in
rat serum after treatment with CsA, the present results suggest that the
contractile effects of IMM 125 and CsG in isolated glomeruli were clearly smaller
compared to CsA, which might reflect the cyclosporins induced GFR changes in
vivo.
PMID- 9641170
TI - Distinct regulation of IL-8 and MCP-1 by LPS and interferon-gamma-treated human
peritoneal macrophages.
AB - BACKGROUND: Interleukin-8 and monocyte chemotactic protein-1 (MCP-1) are major
leukocyte chemoattractants during bacterial peritonitis by recruiting neutrophils
and monocytes/macrophages respectively. METHODS: Peritoneal macrophages (PM) from
12 different CAPD patients with peritonitis were stimulated with either 10 ng/ml
LPS, 10 ng/ml IFN-gamma or LPS+IFN-gamma, and IL-8 and MCP-1 production was
determined on protein and mRNA levels by using ELISA technique and Northern blot
analysis. To obtain information from two different stages of activation,
experiments were done with highly activated PM directly after isolation and with
cells after 10 days in culture, each group being stimulated for 4 h. Unstimulated
cells served as control. RESULTS: Immediately after isolation IL-8 mRNA
expression and synthesis was high and could be further increased by LPS
stimulation, whereas IFN-gamma treatment showed no significant influence. The
levels of MCP-1 were also initially high but could not be further stimulated by
LPS, whereas addition of IFN-gamma resulted in a significant rise in MCP-1
synthesis. After 10 days in culture LPS-stimulation of cells again revealed a
significant increase in IL 8 protein synthesis, whereas IFN-gamma showed no
effect. LPS anergy for MCP-1 was still seen in PM after 10 days in culture, and
IFN-gamma treatment again induced a significant rise in MCP-1 synthesis. The
overall production of both chemokines was far higher on day 1 compared to day 10.
CONCLUSION: Our data show differences in LPS/IFN-gamma regulation for IL-8 and
MCP-1 in both highly activated and in resting, mature peritoneal macrophages,
suggesting distinct pathways for these chemokines that may offer a means of
control for the specific recruitment of neutrophils and monocytes/macrophages in
bacterial peritonitis.
PMID- 9641171
TI - Modulation of transgene expression in mesothelial cells by activation of an
inducible promoter.
AB - BACKGROUND: The efficacy of peritoneal dialysis and its success as a long-term
treatment depends on the preservation of the integrity of the peritoneal
membrane. With increasing time on dialysis, the membrane may become compromised
resulting in decreased dialysing capacity. We have pursued an innovative
strategy, i.e. genetic modification of the mesothelial cell to change the
properties of the membrane to potentially improve its dialysing capacity and
longevity, and have demonstrated the feasibility of this approach in a rat model
of ex vivo gene transfer. The potential to regulate transgene expression in this
model is examined here. METHODS: Rat peritoneal mesothelial cells (MCs) were
stably modified to express human growth hormone (hGH) under control of the heavy
metal ion and glucocorticoid-regulatable murine metallothionein-1 promoter. The
effect of zinc and the synthetic glucocorticoid dexamethasone on hGH expression
was analysed in MC clones maintained in continuous passage or stationary phase,
and in our rat model of ex vivo gene transfer. RESULTS: Exposure of these clones
to zinc and dexamethasone, either singly or in combination, resulted in
significant (i.e. 2-200-fold) increases in hGH production. Zinc-induced
modulation of hGH production was demonstrated in cells in continuous passage and
stationary culture. Regulation was also demonstrated after ex vivo gene transfer
by both the intraperitoneal administration of zinc ions or the systemic
administration of dexamethasone. CONCLUSIONS: Our results demonstrate the
modulation of transgene expression in MCs in vitro and in vivo, and suggest the
potential for the regulation of gene expression in a genetically modified
mesothelium that may ultimately be used for the delivery of therapeutic proteins
to maintain peritoneal membrane viability in the peritoneal dialysis patient.
PMID- 9641172
TI - Differences between women and men with chronic renal disease.
AB - BACKGROUND: The purpose of the present study was to compare the participation of
women and men in the protocols of the Modification of Diet in Renal Disease
(MDRD) study, a multicenter prospective randomized clinical trial, and to assess
gender differences in their renal outcomes. METHODS: Of the 840 participants in
the MDRD study, 332 (39.5%) were women who were assigned randomly to the dietary
protein and blood pressure groups and followed for a median of 2.2 years. A
subgroup analysis of the MDRD study database was carried out to compare women and
men participants in recruitment, baseline characteristics, adherence to protocol
requirements, safety and outcomes, and progression of renal disease and its
response to dietary and blood pressure interventions. RESULTS: Adherence by women
to the requirements of the protocol including diet, record keeping, office
visits, glomerular filtration rate (GFR) measurements and urine collections was
equivalent to that of men. Women had different renal diagnoses, less proteinuria
and lower serum creatinine levels for given GFRs than men. When participants were
grouped above and below age 52, the younger women had lower mean arterial
pressure than did the men. Older women compared with younger had higher mean
arterial pressure, body weight and body mass index, and total low density
lipoprotein cholesterol. These differences were not seen between males of the
same two age groups. During follow-up, the rate of GFR fall was slower in women,
especially in the younger group. However, the association between gender and the
rate of fall in GFR was attenuated and became non-significant after adjusting for
differences in blood pressure, proteinuria and high density lipoprotein
cholesterol. In analyses of the full cohort, there were no significant
differences between women and men in the effects of the low protein or low blood
pressure intervention in patients with either moderate (study A) or advanced
(study B) renal disease. However, in subgroup analyses of patients in study A,
there was some evidence of a lesser effect in women than in men. CONCLUSIONS:
This exploratory analysis of the MDRD study indicates a slower mean GFR decline
in women as compared with men. The slower mean GFR decline and suggestive
evidence of a lesser beneficial effect of the low protein diet and low blood
pressure interventions in women suggest that gender differences should be
considered in trials of the effects of these interventions on the progression of
renal disease. Also, the participation of women in the MDRD study was excellent
and equivalent to that of men.
PMID- 9641173
TI - Long-term outcome according to renal histological lesions in 118 patients with
monoclonal gammopathies.
AB - BACKGROUND: The prognosis of monoclonal gammopathies with multiple myeloma and
renal involvement is poor, and the indication for renal replacement therapy is
controversial. Few studies address the value of renal histology for determining
prognosis according to initial pathology findings. METHODS: We studied the course
of 118 patients with multiple myeloma according to renal biopsy lesions. The
monoclonal component was identified and quantified in serum and urine. Tumor cell
mass was classified as stage 1, 2 or 3, according to Durie and Salmon. End-points
were death, or survival on dialysis, or serum creatinine level at last
examination. RESULTS: Renal biopsy showed myeloma kidney in 48 cases (41%), AL
amyloidosis in 35 (30%), light chain deposit disease in 22 (19%), chronic
tubulointerstitial nephritis in 12 (10%) and cryoglobulinaemic kidney with
multiple myeloma in 1. Maintenance haemodialysis was required in 46 patients
(39%), earlier (P<0.0001) in myeloma kidney (mean: 3 months after diagnosis) than
in AL-amyloidosis (mean: 15 months) and light chain deposit disease (mean: 18
months). Median survival was 12 months in myeloma kidney, 24 months in AL
amyloidosis and 48 months in light chain deposit disease. Dialysis increased
survival in light chain deposit disease, in contrast with myeloma kidney and AL
amyloidosis patients whose survival was shorter when dialysed. The main cause of
death during first year of dialysis was cardiac involvement in AL-amyloidosis,
and sepsis or cardiac insufficiency in myeloma kidney. There was a trend to
increased survival with multidrug chemotherapy which seemed to slow progression
to end-stage renal failure. At last follow-up (median: 12 months, range 1-297),
65 (55%) patients had died. By multivariate analysis, independent predictors of
survival were: age < 70, serum creatinine < or = 300 micromol/l, and serum
calcium < or = 2.5 mmol/l. CONCLUSIONS: Initial renal biopsy helps predict
prognosis in patients with multiple myeloma and renal involvement. Maintenance
haemodialysis is a reasonable indication in light chain deposit disease and AL
amyloidosis, especially in patients aged < 70. Multidrug therapy tends to prolong
survival and slow progression to end-stage renal disease.
PMID- 9641174
TI - Intestinal absorption and biliary secretion of cholesterol in rats with nephrotic
syndrome.
AB - BACKGROUND: Nephrotic syndrome (NS) results in hypercholesterolemia which is
attributed to increased production and decreased removal of cholesterol-rich
lipoproteins. Adjustments in intestinal absorption are reportedly involved in
cholesterol homeostasis. We, therefore, studied the intestinal absorption and
biliary excretion of cholesterol in NS. METHODS: We studied intestinal absorption
(by in vivo perfusion and in vitro everted sac incubation techniques) and biliary
secretion (by common bile duct cannulation) of cholesterol in rats with puromycin
induced NS. The results were compared with those obtained from pair-fed control
(PF) animals, those given free access to food (NL) or those fed a
hypercholerolemic diet (H-chol group). Micellar solutions of Krebs' phosphate
buffer containing trace amounts of [14C]inulin and [3H]cholesterol, as well as
different concentrations of unlabeled cholesterol, were used for absorption
studies. RESULTS: The NS and H-chol groups showed severe and comparable
hypercholesterolemia. No significant difference was found in the rate of biliary
cholesterol secretion among the study groups. Likewise, the rates of in vivo and
in vitro cholesterol absorptions in the NS and H-chol groups were comparable with
one another and similar to those found in the NL and PF groups. The rate of in
vitro cholesterol absorption was directly proportional to its concentration in
the incubation media at low concentrations. However, the absorption rate showed a
pattern consistent with saturable transport at high cholesterol concentrations in
all groups. CONCLUSIONS: We conclude that intestinal absorption and biliary
secretion of cholesterol are not appreciably influenced by either nephrotic or
diet-induced hypercholesterolemia in rats. The data further suggest that
cholesterol absorption may be a saturable process.
PMID- 9641175
TI - Effects of two low-flux cellulose acetate dialysers on plasma lipids and
lipoproteins--a cross-over trial.
AB - BACKGROUND: Studies have shown a beneficial effect of high-flux dialysis on
lipids, lipoproteins and lipoprotein lipase (Lpl) activity. This has been
attributed to improved clearance of Lpl-inhibitory molecules of middle molecular
weight, but differences in flux or biocompatibility have not been addressed. We
conducted a blinded cross-over trial of two cellulose acetate dialysers (AN140,
Althin Medical Inc. and CA210, Baxter Inc.) of similar flux (11 ml/h/mmHg
transmembrane pressure) but with different clearances of larger molecules [AN140
sieving coefficient at mol. wt 11,000 Da (beta2-microglobulin) 0.6; CA210 sieving
coefficient negligible]. METHODS: Sixteen patients were divided into two groups
to receive dialysis with AN140 for 1 week followed by CA210 or vice versa. Before
and after the third dialysis with each membrane, plasma lipid and lipoprotein
concentrations were measured. Post-dialysis post-heparin lipase activity was
measured in six patients. RESULTS: Fifteen patients completed the study. No
difference between dialysers was found for apolipoprotein (apo) A1, B or total
cholesterol measurements. The rise in triglyceride post-dialysis was attenuated
by AN140 (rise 0.05 +/- 0.4 mmol/l vs CA210 0.44 +/- 0.54 mmol/l, P=0.03), while
high density lipoprotein (HDL) cholesterol was increased by AN140 (rise 0.18 +/-
0.12 mmol/l vs CA210 0.06 +/- 0.14 mmol/l, P<0.02). ApoE rose with AN140 during
dialysis but declined with CA210 (1.10 +/- 1.06 mg/dl and -0.77 +/- 0.63 mg/dl,
P=0.002) as did apoCIII (HDL) (AN140 rise 1.33 +/- 2.06 mg/dl; CA210 fall -0.67
+/- 0.73 mg/dl, P=0.001). Lpl activity, measured in six patients, tended to be
higher for AN140 (45.3 +/- 10.5 mmol FFA/ml plasma/h vs CA210 (37.2 +/- 7.9 mmol
FFA/ml plasma/h) (P=0.16). CONCLUSIONS: We conclude that low-flux dialysis using
a cellulose acetate membrane with good clearance of higher molecular weight
molecules may be associated with beneficial changes in plasma lipids and
lipoproteins.
PMID- 9641176
TI - Removal of cytokines and activated complement components in an experimental model
of continuous plasma filtration coupled with sorbent adsorption.
AB - BACKGROUND: Sepsis is associated with enhanced cytokine production. Here, we
examined the in vitro removal of plasma cytokines during continuous
plasmafiltration coupled with sorbent adsorption. METHODS: Proinflammatory
(tumour necrosis factor-alpha, interleukins-1, -8) and anti-inflammatory
(interleukin 1 receptor antagonist, soluble tumour necrosis factor receptor type
I and II) cytokines in whole blood spiked with Escherichia coli endotoxin were
determined during 2-h recirculation in the ultrafiltrate (condition A), plasma
filtrate (condition B), before and after different sorbents (of the Amberlite-,
Amberchrome- Ambersorb -type and charcoal). We studied the maximal adsorbing
capacity, the 1% leakage test for cytokines and C3a des Arg and the adsorption of
complement-dependent leukocyte chemiluminescence. Plasma proteins eluted from the
resins were examined by sodium dodecyl sulphate polyacrylamide gel
electrophoresis and immunoblotting with an anti-human alpha2-macroglobulin.
RESULTS: In condition B, we observed a 40- and 121-fold % increase (vs condition
A) in the removed mass and clearance of tumour necrosis factor-alpha. For all
other cytokines, the removed mass and the clearance increased from 2.3- up to 6
fold. The Amberchrome but not the Amberlite or Ambersorb resins could remove the
highest amount of cytokines and could reduce complement-dependent
chemiluminescence. Two protein bands of approximately 400,000 D and 200,000 D
were eluted only from Amberchrome resins and immunoprecipitated by anti-human
alpha2-macroglobulin and anti-human C3c antibodies, respectively. CONCLUSIONS:
These studies suggest an efficient removal of cytokines in continuous
plasmafiltration with sorbent adsorption. The binding of alpha2-macroglobulin, a
carrier of cytokines in plasma, might be a additional mechanism in the removal of
cytokines from plasma.
PMID- 9641177
TI - Alterations of synovial tissue and their potential role in the deposition of
beta2-microglobulin-associated amyloid.
AB - BACKGROUND: Beta-2-microglobulin-associated amyloidosis (AB2M) is a frequent
complication of long-term dialysis treatment. Uraemic retention of beta2
microglobulin (beta2M) apparently constitutes the basis for AB2M. However, it is
unclear why clinical manifestations are largely confined to osteoarticular
tissues. It has been speculated that synovial inflammatory changes, induced by
uraemia and/or dialysis therapy could predispose this tissue to amyloid
deposition. METHODS: We investigated which local synovial alterations preceded or
paralleled amyloid deposition. Using immunohistology we evaluated synovial
leukocyte infiltration (B and T lymphocytes, monocytes/macrophages), cell
proliferation, fibroblast activation (de novo expression of alpha-smooth-muscle
actin), the expression of extracellular matrix components (heparan sulphate
proteoglycan, collagen types I, III, IV), and advanced glycation end-products
(AGEs). RESULTS: Synovial AB2M was detected in 20 of 36 chronic peritoneal and
haemodialysis patients and none of eight non-uraemic controls. Notably, non-AB2M
synovial amyloid was present in six additional dialysis and three control
patients. Cellular infiltration was largely restricted to patients with advanced
AB2M deposits. The infiltrates consisted mainly of macrophages and progressed
with increasing degrees of AB2M deposition. In advanced cases they exhibited
characteristics of a foreign-body reaction. Other infiltrating leukocyte types,
altered cell proliferation, or fibroblast activation were absent or uncommon in
periarticular tissue of dialysis patients with and without AB2M. Neither dialysis
treatment nor the presence of AB2M deposits appreciably altered the qualitative
matrix composition in periarticular tissue. AGEs were present in AB2M deposits,
the extracellular synovial matrix of dialysis patients (of both, patients with
and without AB2M) and, to a lesser degree, in synovia of controls. CONCLUSIONS:
These data suggest that, except for AGE formation, alterations of none of the
parameters assessed, and in particular no inflammatory tissue alterations,
precede periarticular AB2M. Rather synovial tissue, possibly modified by AGEs,
seems to have an intrinsic propensity for amyloid deposition and inflammatory
changes appear to only arise secondary to amyloid deposition.
PMID- 9641178
TI - Anorexigen (TNF-alpha, cholecystokinin) and orexigen (neuropeptide Y) plasma
levels in peritoneal dialysis (PD) patients: their relationship with nutritional
parameters.
AB - BACKGROUND: Malnutrition has definitely been related to mortality among dialysis
patients. Persistent loss of appetite is one of the major symptoms found in these
patients. It is also well recognized that several substances produce anorexia or
disorders of the hunger-satiety cycle in several diseases. The aim of this study
was to identify the role of anorexigen substances (TNF-alpha and cholecystokinin
or CCK) and an orexigen substance (neuropeptide Y or NPY) in anorexia and
malnutrition among 55 clinically stable peritoneal dialysis (PD) patients.
RESULTS: High TNF-alpha plasma levels were found in 41 of 42 patients (97.6%)
with a mean of 70.5+/-32.3 pg/ml. Patients with anorexia (n=11) or anorexia with
nausea or vomiting (n=5) had higher TNF-alpha values than patients without these
symptoms (75.9+/-34 vs 52.1 +/-24.5 pg/ml, P<0.05). Eight patients with a prior
diagnosis of acid pylori disease showed higher TNF-alpha values (87.2+/-24.3)
than 30 unaffected patients (63.6+/-30.5, P<0.05). TNF-alpha showed a significant
negative linear correlation with retinol binding protein (RBP) (r=-0.37, n=34,
P<0.05), and venous pH (r=-0.4, n=42, P<0.01); also, TNF-alpha values higher than
65 pg/ml were inversely associated with transferrin, cholesterol, blood urea
nitrogen (BUN) and CCK. Patients with prealbumin levels lower than 30 mg/dl, a
BMI lower than 30 kg/m2, nPCR lower than 1.1 g/kg/day and urea KT/V lower than
2.2 showed higher serum TNF-alpha levels. Patients who had been on CAPD treatment
for longer periods showed higher TNF-alpha values. High plasma CCK levels were
found in 38 of 45 patients (84%), mean 45.9+/-32.3 pg/ml. Patients with anorexia
had no difference in CCK values compared with those without. A direct association
was found between CCK levels and some nutritional markers (albumin, fibronectin,
triglycerides, folic acid and nPCR in non diabetic patients). Although CCK has a
recognized anorectic effect, this direct association might be because of an
abnormal stimulation of CCK glucose feedback (trypsin) due to continuous
peritoneal glucose absorption. This suggests that CCK could be an immediate food
intake marker in PD patients. The NPY plasma levels were normal in 33 patients,
high in 6 and low in 11. Patients with anorexia showed lower NPY levels than
those without. NPY values greater than 50 pg/ml were directly associated with
higher transferrin, prealbumin, RBP, nPCR and urea KT/V values. Importantly, a
negative linear correlation between NPY and TNF-alpha was found (r=-0.42, n= 41,
P<0.01). There was no significant relationship between residual renal clearance
and the serum levels of the three peptides. CONCLUSION: In conclusion, our data
suggest that high TNF-alpha and low NPY serum levels are associated with
anorexia. High TNF-alpha, low CCK and low NPY serum levels are also related to a
poor nutritional status. Further research on these circulating substances is
required.
PMID- 9641179
TI - Nutritional assessment of children on haemodialysis: value of IGF-I, TNF-alpha
and IL-1beta.
AB - BACKGROUND: Protein-energy malnutrition (PEM) is associated with increased
morbidity and mortality in haemodialysis (HD) patients. Insulin-like growth
factor I (IGF-I) has proved to be a sensitive marker of malnutrition, while
interleukin-1 (IL-1beta) and tumour necrosis factor (TNF) have been found to be
raised in catabolic states. METHODS: We have investigated the nutritional status
of 17 chronic renal failure (CRF) paediatric patients (8 boys, 9 girls) on
maintenance HD. Eight predialysis CRF children (5 boys and 3 girls; mean
creatinine 5.1+/-3.2 mg/dl) and 10 healthy children served as control groups. PEM
was defined according to anthropometric measurements (triceps skinfold thickness
(TST), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC)).
These were correlated with serum IGF-I, IL-1, TNF-alpha, transferrin, and albumin
(all sampled before the HD session). RESULTS: In the HD group, TST was reduced in
41.2% of the patients, whereas MAC and MAMC were reduced in 82.4 and 76.5%
respectively. TST was depleted in only one of the predialysis CRF children. The
degree of reduction in MAC and MAMC were 62.5 and 62.5% respectively. Median
serum IGF-I level was decreased in both HD and predialysis CRF patients (205.1
interquartile range (IQR) 194.4 microg/l and 258.8 IQR 155.0 microg/l
respectively) compared to the healthy children (418.0 IQR 310.5 microg/l)
(P=0.0009 and P=0.01 respectively). Within the HD group, IGF-I levels were lower
in patients with malnutrition defined according to TST (145.0 IQR 125.5 microg/l)
compared to children with normal TST (301.2 IQR 218.8 microg/l) (P=0.05). IGF-I
levels of the HD patients with malnutrition according to TST was also lower than
the predialysis CRF patients and healthy children (P=0.04 and P=0.002
respectively). Serum IL-1beta was undetectable in all groups. Median serum TNF
alpha levels were higher in HD and predialysis CRF patients compared to healthy
children, albeit statistically insignificant. There was no correlation between
TNF-alpha, transferrin or albumin and anthropometric parameters. CONCLUSIONS: Our
results support the high prevalence of malnutrition in CRF children, which
becomes more pronounced when treatment by HD is initiated. We suggest that
determination of IGF-I levels in childhood HD patients in conjunction with
anthropometric measurements is useful for identification of malnutrition. We have
not been able to demonstrate the catabolic effects of cytokines on this state of
protein energy malnutrition.
PMID- 9641180
TI - Regression of left ventricular hypertrophy in haemodialysis patients by
ultrafiltration and reduced salt intake without antihypertensive drugs.
AB - BACKGROUND: Left ventricular hypertrophy (LVH) is very frequent in haemodialysis
patients. Only few investigations have reported its regression, and only by the
use of antihypertensive drugs. Because volume load is at least as important as
pressure load, we investigated whether persistent strict volume control by
ultrafiltration alone may be effective in improving LVH METHODS: Using blood
pressure (BP) and cardiac dimensions as a guide, we treated all hypertensive
patients in our dialysis unit during the 3 times weekly dialysis sessions for 4 h
per session with as much ultrafiltration as they could stand. If they gained too
much weight an extra isolated ultrafiltration (UF) session was applied. Special
attention was given to dietary salt restriction. The study group of all 15
patients in whom echocardiographic assessment had been made at least 1.5 years
previously was selected retrospectively, and we acknowledge that important
confounding factors might not have been controlled for. Cardiothoracic index
(CTI) was estimated on the chest X-ray. Diameters of left atrium (LA), left
ventricle systolic (LVS) and diastolic (LVD), interventricular septum (IVS),
posterior wall (PW), and left ventricular mass index (LVMI) were estimated by
standard echocardiographic methods. RESULTS: Mean arterial pressure of the study
group had been lowered by UF before the first echocardiogram from predialysis
136+/-11 to 101+/-14 and from postdialysis 119+/-8 to 92+/-12 mmHg. During a mean
follow-up period of 37+/-11 months LVMI decreased from 175+/-60 to 105+/-11 g/m2.
CTI decreased further from 48+/-3 to 43+/-4%, while significant decreases of LA
(22.5+/-3 to 19.9+/-4 mm/m2), LVS (18.7+/-4 to 15.9+/-3 mm/m2) and LVD (28.3+/-4
to 24.0+/-3 mm/m2) were seen in all patients. There also was a further decrease
in both pre- and postdialysis BP to 116+/-12/73+/-7 and 105+/-7/65+/-3 mmHg
respectively. CONCLUSION: The results of this uncontrolled retrospective study
suggest that good long-term BP control and a decrease of LVM can be achieved by
continuous efforts to control hypervolaemia. The decrease in volume may be even
more important than pressure reduction to achieve this goal.
PMID- 9641181
TI - Role of the donor in post-transplant renal function.
AB - BACKGROUND: The donor, i.e. adult or paediatric, might influence the outcome of
the graft function. METHODS: The glomerular filtration rate (GFR) of 120
transplanted children (47 girls) aged 10.4+/-4.6 years (0.7-17.2) was
prospectively assessed over a 5-year period. The patients were divided into two
groups according to the age of donor: adult (donor age > 18 years; n=33) and
paediatric (donor age < 18 years; n=87). GFR was assessed by inulin clearance at
3, 6 and 12 months and yearly thereafter. RESULTS: The average GFR was stable in
the range of 70 ml/min/1.73 m2 for the whole follow-up period. The adjusted GFR
in adult graft recipients was significantly higher at 3 months post
transplantation: 80.6+/-36.9 vs 65.1+/-22.0, P=0.02. However, from the second
year post-transplantation, the adjusted GFR in paediatric graft recipients became
significantly higher than that of adult graft recipients. Such results could be
due to an improvement in the absolute GFR (ml/min) of paediatric graft recipients
with time (P=0.0001) whereas that of the adult graft recipients remained stable
despite the children's growth. CONCLUSIONS: The adjusted GFR of adult graft
recipients was significantly higher than that of paediatric graft recipients in
the early post-transplant period. In the long-term, a progressive decrease in
adjusted GFR was noted in adult graft recipients. On the one hand, this may be
due to a functional adaptation and/or inadequate compensatory growth of the
graft. On the other hand, the absolute GFR of paediatric graft recipients
increased, suggesting an ongoing capacity for growth and/or compensatory
hypertrophy after child-to-child renal transplantation.
PMID- 9641182
TI - Pre-operative echocardiographic abnormalities and adverse outcome following renal
transplantation.
AB - BACKGROUND: Premature cardiovascular disease is now the leading cause of death in
renal transplant recipients. Although patients with progressive renal disease
have many of the conventional risk factors for cardiovascular disease these do
not have the same predictive power as they do in the general population.
Echocardiographic abnormalities, notably left ventricular hypertrophy, have been
shown to be associated with adverse outcome in patients on dialysis. METHODS: The
echocardiograms were studied from 141 patients who were examined on the eve of
renal transplantation between 1988 and 1990 to try to identify factors predicting
outcome. Thirty-four patients have since died, 22 of cardiovascular disease.
Ninety-three of the survivors and 27 of the dead patients had echocardiographic
traces suitable for analysis. RESULTS: Left ventricular mass index was increased
in those patients who died (median 167 vs 134 g/m2; P=0.03), as were end-systolic
(4.3 vs 3.4 cm; P<0.01) and end-diastolic (5.8 vs 5.2 cm; P<0.01) diameters.
Systolic function was also more severely impaired (fractional shortening, 27 vs
33%; P<0.01). Apart from age, only systolic function and end systolic diameter
were independent predictors of outcome in multivariate analysis. CONCLUSIONS:
This pattern of echocardiographic abnormality is similar to that reported in long
term dialysis populations, despite the adverse effects on survival. Moreover,
despite potential benefits of transplantation on cardiac function, left
ventricular hypertrophy, ventricular dilatation and systolic dysfunction were all
associated with adverse outcome following transplantation. We conclude that
echocardiography identifies markers for premature death following transplantation
and provides targets for therapeutic intervention.
PMID- 9641183
TI - Renal transplantation in the management of bilateral Wilms' tumour (BWT) and of
Denys-Drash syndrome (DDS).
AB - BACKGROUND: Wilms' tumour (WT) occurs bilaterally in approximately 5-7% of
affected children. In some patients, complete surgical removal of the malignant
tissue cannot be achieved without bilateral total nephrectomy. In Denys-Drash
syndrome (DDS), bilateral nephrectomy is indicated both because of the associated
nephropathy usually progressing rapidly to end-stage renal failure and because of
the high risk of WT development in any residual renal tissue. METHODS: Case
records of patients with a diagnosis of either bilateral WT (BWT) or DDS, who
underwent bilateral nephrectomy and subsequent renal transplantation between 1980
and 1996 at the Hospital for Sick Children, London, were reviewed. RESULTS:
Allogeneic renal transplantation was performed in two children with BWT and four
with DDS, three of whom had developed unilateral WT by the time their kidneys
were removed. Renal transplantation was performed 15-49 months after bilateral
nephrectomy at a mean age of 45 (26-76) months, with a minimum of 1 year tumour
free survival after completion of chemotherapy in those with WT. One patient died
after renal transplantation. Five children had a favourable outcome, with a mean
follow-up of 80 (29-121) months post-renal transplantation. CONCLUSION: Advances
in dialysis and transplantation programmes for young children offer the potential
for a marked improvement in the prognosis for patients with BWT and for those
with DDS.
PMID- 9641184
TI - Body composition in patients treated with peritoneal dialysis.
AB - BACKGROUND: Malnutrition is a common complication in uremia and during
maintenance dialysis. Several factors contribute to its development. Different
modes of dialysis treatment may differ in their effects on nutritional status.
METHODS: In order to analyse the nutritional consequences of peritoneal dialysis
(PD), body composition analyses were performed in PD patients between February
1993 and March 1996. Body cell mass (BCM) was estimated from measurements of
total body potassium (TBK) in a whole-body counter. Total body water (TBW) was
determined by measurement of tritiated water. Body fat (BF) was calculated from
body weight (BW), TBK and TBW. Observed values were related to predicted (o/p)
derived from local population studies. RESULTS: Sixty patients were repeatedly
investigated during the study period. Of these, 34 were investigated during the
first year of PD. At the start of dialysis, TBK o/p was 0.94 and BF o/p 0.76. No
change in body composition was seen during the observation period in the group as
a whole. However, within the group individual changes in BW were strongly
correlated with individual changes in BF (r=0.66, P=0.0001). Twenty-six patients
were examined during the second and third year of PD. In this group, BW o/p
remained constant over time. However, there was a small but significant decline
of TBK o/p and a concomitant increase of BF o/p (P<0.05). No correlation was
observed between changes in TBK and changes in serum albumin. CONCLUSIONS: The
results of this study indicate, that there may be a risk for further reduction of
body cell mass during long-term PD treatment, while body energy stores are
maintained or even increased.
PMID- 9641185
TI - Use of the Valsalva manoeuvre to identify haemodialysis patients at risk of
congestive heart failure.
AB - BACKGROUND: In the presence of elevated cardiac filling pressures, the decline of
blood pressure (BP) during the straining phase of a Valsalva manoeuvre is blunted
or absent. We compared the use of non-invasively measured BP response to a
Valsalva manoeuvre with clinical assessment and bioimpedance measurements to
identify haemodialysis patients at risk of acute congestive heart failure (CHF).
METHODS: Continuous BP response (Finapres) to a Valsalva manoeuvre, clinical
assessment by nephrologists, and bioimpedance estimations of extracellular fluid
volume were determined before and after haemodialysis, once every week during a 5
week period. Acute CHF was defined according to preset clinical and radiological
criteria. RESULTS: Participants (age 60+/-19 years, six females, nine males) had
an average predialysis weight of 66.8+/-11.8 kg. Patients were dialysed for 3.8+/
0.8 h with a mean ultrafiltration of 2.4+/-1.1 litres. Valsalva systolic BP
ratios (phase 2 to 1) decreased significantly during dialysis from 0.81+/-0.11 to
0.73+/-0.10 (P<0.05). Five patients experienced an episode of acute CHF. The
Valsalva BP ratios for these patients before and after dialysis (0.89+/-0.05 and
0.78+/-0.05 respectively) were higher than for the remaining ten patients (0.77+/
0.10 and 0.70+/-0.11, respectively) (P<0.05). A cutoff Valsalva BP ratio of 0.82
resulted in positive and negative predictive values for CHF of 62 and 100%
respectively. No differences in clinical assessment or bioimpedance parameters
were found, with the exception of postdialysis diastolic BP and predialysis ankle
oedema. After treatment of CHF, Valsalva BP ratios decreased significantly
without changes in the other hydration parameters. CONCLUSIONS: Non-invasive
assessment of the BP response to a Valsalva manoeuvre appears to be a potential
tool for identifying patients at risk of acute CHF during maintenance
haemodialysis.
PMID- 9641186
TI - Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit
patients with focal segmental glomerulosclerosis?
AB - DESIGN: Eleven adult patients with biopsy-proven primary FSGS and nephrotic
syndrome resistant to steroids and cytotoxic drugs were treated with
plasmapheresis in addition to oral prednisolone and intravenous cyclophosphamide.
On the average each patient had undergone 17 sessions over a period of 15-25
weeks (mean 21.90+/-2.71 weeks). RESULTS: One month after the last plasmapheresis
session, 72.7% (n=8) of the patients were in clinical remission of nephrotic
syndrome in association with the stabilization of renal function. In contrast,
patients who did not respond 27.3% (n=3) had a gradual decline in renal function.
After a mean follow-up of 27.45+/-6.31 months, six patients who responded (54.5%)
remained in sustained complete or partial remission of proteinuria with stable
renal function. The mean proteinuria at the latest examination was 0.9+/-0.01 g
per day in these patients. CONCLUSION: It is concluded that a combination of
plasmapheresis, corticosteroids, and cyclophosphamide may obtain sustained
improvement of proteinuria and stabilization of plasma creatinine in about half
of the patients who proved to be refractory to therapy.
PMID- 9641187
TI - The effect of recombinant human growth hormone treatment on bone and mineral
metabolism in haemodialysis patients.
AB - BACKGROUND: Uraemia and chronical haemodialysis are associated with an abnormal
growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to
malnutrition and renal bone disease. Short-term studies have shown a beneficial
effect of treatment with recombinant human growth hormone (rhGH) on nutritional
status in patients on haemodialysis. In the present study, we evaluated the
effect of rhGH on bone and mineral metabolism. METHODS: Twenty chronic
malnourished patients on haemodialysis took part in a double-blind, placebo
controlled trial with subcutaneous injections of rhGH (4 IU/m2/day) or placebo
for 6 months. RESULTS: During rhGH treatment, serum IGF-1 increased 264 +/- 52%
(mean +/- SEM) (P < 0.008). There were no significant changes in biochemical
markers of mineral metabolism (serum ionized calcium, phosphate and parathyroid
hormone). Among markers of bone metabolism, there was a significant increase in
serum procollagen type I C-terminal propeptide (maximum 155 +/- 8%, P < 0.001)
and no significant changes in serum alkaline phosphatase. Bone densitometry
showed a significant decrease in whole body bone mineral content (95.7 +/- 1.2%)
after 6 months treatment. The effects on the proximal femur were not significant.
CONCLUSION: The effects of 6 months treatment with rhGH seen in this study are
best explained by a GH- or IGF-1-induced increased bone turnover. Long-term
treatment in larger cohorts followed by bone densitometry and, preferentially,
bone histomorphometry are needed to evaluate whether this is a beneficial effect
in haemodialysis patients.
PMID- 9641188
TI - Removal of morphine with the new high-efficiency and high-flux membranes during
haemofiltration and haemodialfiltration.
AB - We present three critically ill patients with severe renal failure who required
haemofiltration or haemodiafiltration, with high-efficiency or high-flux
membranes, while receiving an intravenous infusion of morphine. We show that
despite the very high ultrafiltrability/diffusability of free morphine, only 1-3%
of the total amount of infused morphine is removed in 24 h. This is in marked
contrast to haemodialysis where, owing to much higher dialysate flow rate, a
significant quantity of free morphine is removed.
PMID- 9641189
TI - Ultrafiltrable aluminium after very low doses of desferrioxamine.
AB - BACKGROUND: The recommended dose of desferrioxamine for the treatment of
aluminium intoxication is 5 mg/kg/week. However, there are no data about the
efficiency of lower doses. The objective of this study was to investigate the
capacity of very low doses of desferrioxamine in the generation of ultrafiltrable
aluminium. METHODS: Five patients undergoing haemodialysis with a similar
biochemical profile and serum aluminium levels >40 microg/l were studied. The
three different doses of desferrioxamine used (0.5, 2.5 and 5.0 mg/kg) were
administered randomly to each patient at 1 week intervals. Total and
ultrafiltrable serum aluminium was measured before and 44 h after the
administration of desferrioxamine. RESULTS: All doses of desferrioxamine
significantly increased the total serum aluminium; no differences were found
between 2.5 and 5.0 mg/kg. The total serum aluminium levels doubled with the 2.5
and 5.0 mg/kg doses, while the increase with 0.5 mg/kg was lower (32.6%, P<0.05).
Ultrafiltrable aluminium increased with the three doses; from 7.1+/-2.8, 3.9+/
0.6 and 7.5+/-4.1 to 25.7+/-7.3, 44.3+/-10.1 and 59.1+/-19.8 microg/l,
respectively (P<0.05). The efficiency of each dose was calculated using the ratio
between the increase in ultrafiltrable aluminium and the dose of desferrioxamine
administered. The efficiency ranged from 10.3+/-3.9 for the higher dose (5 mg/kg)
to 37.2+/-10.3 for the lower dose (0.5 mg/kg). CONCLUSIONS: Our results suggest
that very low-dose desferrioxamine (>5 mg/kg) increases the ultrafiltrable
(potentially dialysable) aluminium.
PMID- 9641190
TI - PCR diagnosis on formalin-fixed, paraffin-embedded tissues with acid-fast stain
and culture negativity in chronic dialysis patients of cervico-mediastinal
tuberculous lymphadenitis.
AB - BACKGROUND: Bacteriologic studies often provide negative results in tuberculous
infection, and do not favour early diagnosis. Polymerase chain reaction (PCR) is
known to diagnose tuberculosis quickly. With this in mind, we used PCR to detect
mycobacterial DNA on formalin-fixed, paraffin-embedded tissues with acid-fast
stain and culture negativity in two dialysis patients with cervico-mediastinal
lymphadenopathy. METHODS: Sections of neck lymph nodes were cut at two different
levels. At each level, two semi-adjacent sections with a thickness of 5 microm
each were cut using standard microtomes with disposable blades. The first section
mounted on a glass slide was stained by Ziehl-Neelsen, and the second section was
examined by PCR based on a 123 bp fragment of IS6110 that is specific for the
Mycobacterium tuberculosis complex. RESULTS: The histology of lymph nodes
disclosed inflammatory necrotizing granulomas, but acid-fast stain for M.
tuberculosis was negative in the two patients. DNA of M. tuberculosis was
detected in lymph node samples from each patient by PCR on the IS6110 element and
by dot-blot hybridization. CONCLUSIONS: PCR assay is a potentially useful
approach for early and rapid diagnosis of tuberculous lymphadenitis in chronic
dialysis patients, since mycobacterial staining and culture often provide
negative results.
PMID- 9641191
TI - Ifosfamide-induced renal Fanconi syndrome with associated nephrogenic diabetes
insipidus in an adult patient.
PMID- 9641192
TI - Reversible renal failure due to specific infiltration of the kidney in chronic
lymphocytic leukaemia.
PMID- 9641193
TI - Disseminated intravascular coagulation complicating polyarteritis nodosa in alpha
1-antitrypsin deficiency.
PMID- 9641194
TI - Antimyeloperoxidase-antibody-positive rapidly progressive glomerulonephritis
associated with Castleman's disease.
PMID- 9641195
TI - Reversal of osteomyelosclerosis-associated systemic lupus nephritis.
PMID- 9641196
TI - Renal artery stenosis and focal segmental glomerulosclerosis in the contralateral
kidney.
PMID- 9641197
TI - Gemella morbillorum--spondylodiscitis in a patient with a renal graft.
PMID- 9641198
TI - Successful kidney retransplantation after combined liver/kidney transplantation
in primary hyperoxaluria type I.
PMID- 9641199
TI - Fatal hepatitis B virus infection with fibrosing cholestatic hepatitis following
renal transplantation.
PMID- 9641200
TI - Hepatitis-B-virus-related fibrosing cholestatic hepatitis after renal
transplantation with acute graft failure following interferon-alpha therapy.
PMID- 9641201
TI - Transplant renal artery aneurysm following venous patch repair of a traction
injury to the renal artery.
PMID- 9641202
TI - An unusual cause of pink urine.
PMID- 9641203
TI - Acute acid-base disorder during plasma immunoadsorption treatment using citrate
anticoagulation.
PMID- 9641204
TI - Intravascular ultrasound to establish the indication for renal angioplasty.
PMID- 9641205
TI - The normoglycaemic patient with nephrotic syndrome.
PMID- 9641206
TI - Malarial nephropathies.
PMID- 9641207
TI - Dialysis fluid composition and quality--professional opinion vs scientific
evidence.
PMID- 9641208
TI - Increased platelet thromboxane release in focal segmental glomerulosclerosis.
PMID- 9641209
TI - Failure of cyclosporine A in controlling Schoenlein-Henoch purpura.
PMID- 9641210
TI - Percutaneous drainage by multiple and bilateral puncture of infected renal cysts
in autosomal dominant polycystic kidney disease.
PMID- 9641211
TI - Chronic renal failure and end-stage renal disease in St Petersburg, Russia.
PMID- 9641212
TI - Recurrent Kaposi's sarcoma in a renal transplant recipient maintained on minimum
doses of immunosuppression.
PMID- 9641213
TI - Sterile leukocyturia as a manifestation of urinary tuberculosis in renal
transplant patients.
PMID- 9641214
TI - The clinical value of digene hybrid capture HPV DNA testing in a referral-based
population with abnormal pap smears.
AB - PURPOSE OF INVESTIGATION: The hybrid capture human papillomavirus (HPV) DNA assay
is offered by the manufacturer to assist clinicians with patients with ASCUS pap
smear results to assess the risk factor and to potentially direct follow-up of
these patients. In our practice, a gynecologic oncology practice that has a
referral based population with abnormal pap smears, our purpose was to evaluate
the patients referred with all grades of abnormal cervical cytology. METHODS: One
hundred consecutive patients who were referred for evaluation of abnormal
cervical cytology: atypical squamous cells of undetermined significance (ASCUS);
low-grade squamous intraepithelial lesion (LGSIL); high-grade squamous
intraepithelial lesion (HGSIL); or squamous cell carcinoma (SCC) were evaluated
by repeat pap smear, hybrid capture HPV DNA analysis and colposcopy. Colposcopic
findings were recorded, and if appropriate, cervical biopsies were performed.
Hybrid capture results were correlated with histologic and cytologic findings.
Using histopathologic diagnosis as the reference standard, the sensitivity and
positive predictive value of pap smear and high risk HPV were calculated. The
Kappa test was used to correlate colposcopic and histopathologic findings.
RESULTS: Repeat pap smears at the time of initial consultation demonstrated 25
patients with normal results, 39 with LGSIL, 30 with HGSIL, 1 SCC and 5 ASCUS.
Seventy-eight patients underwent cervical biopsy. Colposcopic findings correlated
significantly with histopathologic findings (p<0.0001). Forty-four percent of
patients tested positive for HPV DNA: 40 patients with high risk HPV, three
patients with low risk HPV, and one patient with both high risk and low risk HPV.
Sixteen of 39 patients (41%) with LGSIL on pap smear tested positive for high
risk HPV; 37% of patients in this group required cervical conization because
cervical biopsies demonstrated moderate/severe dysplasia. The diagnosis of
moderate/severe dysplasia significantly correlated with the presence of high risk
HPV [OR 78.9 (8.31-389.30)]. There was no significant correlation between the HPV
DNA signal strengths and the histologic grade of dysplasia. The sensitivity and
the positive predictive value of pap smear alone in identifying moderate/severe
dysplasia was 62% and 96%, respectively. The combination of HGSIL pap smears and
high risk HPV increased the sensitivity but not the positive predictive value for
the detection of moderate/severe dysplasia to 77.7% and 95%, respectively (P=NS).
CONCLUSIONS: Although in this setting, the use of hybrid capture DNA testing did
not significantly improve the sensitivity or positive predictive value of the
diagnosis of HGSIL cytology when compared to cytologically indicated plus
colposcopically directed cervical biopsies in this population of women at high
risk for the presence of disease, the combination of HGSIL pap smears and high
risk HPV did result in a clinically important increase in the diagnosis of
moderate/severe dysplasia.
PMID- 9641216
TI - Radical abdominal hysterectomy using the ENDO-GIA stapler: report of 150 cases
and literature review.
AB - Over a seven-year period from 1990-1997 150 consecutive patients underwent Type
III radical abdominal hysterectomy using the ENDO-GIA stapler on the cardinal and
uterosacral ligaments. Compared to prior patients operated on with standard
suturing methods, the stapler patients had shorter operating times, lower blood
loss and infection rates, and shorter hospital stays without any increase in
recurrence rate. The equipment failure rate was 3%. Although not all improvements
in surgical and post-operative morbidity are likely due to use of the ENDO-GIA
stapler, the use of the stapler clearly lowered operating times, blood loss,
surgical morbidity, hospital stay with no adverse effect on patient survival.
PMID- 9641215
TI - Predictors of co-incidental CIN II/III amongst a cohort of women with CIN I
detected by a screening Pap test.
AB - Approximately 20-40% of lesions interpreted by a screening Pap test as CIN I and
subsequently examined by colposcopy include a co-incidental CIN II/III. Since the
HPV profiles of CIN I and CIN II/III differ, HPV typing may predict these co
incidental higher grade lesions. Based on both the colposcopic impression and
repeat Pap test, 537 women referred for examination of CIN I as classified by a
screening Pap test were triaged into group A (= CIN I) or group B (>/= CIN II).
Clinical, demographic, reproductive, and risk factor data was collected by
questionnaire and HPV typing of cervical scrapes was done by PCR. Group A
included 342 (63.7%) women and group B 195 (36.3%). Group B women more frequently
were current cigarette smokers (p<0.001) and had a high school or lesser level of
education (p=0.04). HPV positivity amongst younger group B women (= 21 years)
and a history of current/occasional cigarette smoking in those 22 years and older
were significant predictors of triaged, co-incidental CIN II/III (p<0.001). This
age restriction will limit the adoption of HPV testing as an universal,
adjunctive test for the identification of CIN II/III amongst CIN I lesions
detected by a screening Pap test. A greater health advantage may be gained by
increasing women's awareness of the risks, including that of cervical cancer
associated with cigarette smoking.
PMID- 9641217
TI - The size of a micrometastasis in the axilla in breast cancer: a study of nodal
tumour-load related to prognosis.
AB - Much has been written on micrometastases to the axilla in breast cancer but there
is no consensus as to their size. In this study three levels of nodal tumour-load
are defined following measurement of nodal tumour area on histology. The two cut
points described are both of clinical interest. The smallest deposits, up to
0.0001 cm2, include embolic growth on the afferent side of the node, which is, as
reported previously, of poor prognosis. In such cases post-operative prognosis
approaches that in the "node-positive", here defined as cases with an axillary
tumour-load of 0.5 cm2 or more. Between these two groups is a collection of
cases, 40% of the total series, with a prognosis similar to the node-negative. It
is suggested that the deposits in this intermediate group should be termed
micrometastases, the high risk cases with embolic growth reported as such and
those with larger deposits as node-positive.
PMID- 9641218
TI - Five-year survival in patients with endometrioid carcinoma of the ovary versus
those with serous carcinoma.
AB - BACKGROUND: Ovarian carcinoma is the most deadly of gynecologic malignancies.
Controversy exists as to whether different histologic types have a different
prognosis. The goal of this study was to determine whether patients with
endometrioid carcinoma of the ovary have a different prognosis than patients with
serous carcinoma. METHODS: Available records for all patients on the gynecologic
oncology service with epithelial ovarian carcinoma from January 1, 1981 through
December 31, 1989, were reviewed. Patients with endometrioid ovarian carcinomas
were matched with patients with serous carcinoma with regards to age, grade,
stage, and level of cytoreduction. RESULTS: Forty-two patients were studied by
matching 21 patients with endometrioid carcinoma with 21 patients with serous
carcinoma. The 5-year survival of the 21 patients with endometrioid carcinoma was
61.9% while the 5-year survival was 71.4% in the patients with serous carcinoma
(P=0.22). Of the patients diagnosed with endometrioid carcinoma, the mean
survival was 57 months versus a mean survival of 69 months in patients with
serous carcinoma (P=0.30). Estrogen receptor levels were not statistically
significantly different between the two groups (P=0.108); however, progesterone
receptor levels did prove to be statistically significantly different (P<0.001).
CONCLUSIONS: When patients with endometrioid and serous tumours of the ovary are
matched for age, grade, stage and level of cytoreduction, there is no difference
in either 5-year survival or length of survival.
PMID- 9641219
TI - Effects of retinoic acid on the expression of a tumor rejection antigen (heat
shock protein gp96) in human cervical cancer.
AB - Retinoids are a class of compounds structurally related to vitamin A which have
been found to be active agents experimentally as well as clinically in the
prevention and treatment of cervical cancer. Recent data have suggested that in
addition to their key regulatory role during epithelial cell differentiation,
they could also contribute to enhanced cellular and humoral immunity against
tumor cells. Hsp gp96 molecules have recently been implicated in the presentation
of tumor and viral antigens. A number of key elements in this pathway, including
major histocompatibility complex (MHC) class I molecules as well as adhesion/co
stimulation molecules such as ICAM-1 have reported to be sensitive to retinoic
acid up-regulation. In this study we analyzed at the transcriptional (Northern
blot) and post-transcriptional levels (Western blot) the effects of retinoic acid
on the expression of the tumor rejection antigen (heat shock protein gp96) in
three human cervical carcinoma cell lines. Exposure of therapeutic doses of
retinoic acid (i.e. 1 microM) significantly and consistently increased the
expression of heat shock protein gp96 (Western blot analysis) on CaSki, SiHa and
HT-3 cervical cancer cell lines. Northern blot analysis demonstrated that the
increase in the amount of protein was due to the transcriptional upregulation of
this gene. Taken together, our results show that retinoic acid can significantly
increase the expression of yet another immunologically important cell molecule,
the tumor rejection antigen heat shock protein gp96 in human cervical cancer.
Such findings provide new information on the effects of retinoic acid on tumor
cells and further support the role of retinoic acid as a powerful biologic
response modifier.
PMID- 9641220
TI - Concurrent cytogenetic and molecular investigations in uterine and ovarian
neoplasms.
AB - We studied a group of 24 uterine and ovarian neoplasms with the purpose to verify
if any correlation could be established between chromosomal abnormalities, loss
of heterozigosity (LOH) and microsatellite instability (MIN). Tumor specimens
obtained from 24 women (12 affected by ovarian and 12 by uterine neoplasms) were
split in two parts, one was used for short term cultures for cytogenetic
investigation while from the second DNA was extracted for molecular studies. We
studied 22 polymorphic loci from 19 chromosomes and compared the alleles observed
in the tumor with those observed in the DNA obtained from peripheral blood.
Extensive loss of heterozigosity was observed when total or partial chromosomal
loss was observed in at least 50% of the examined cells; MIN did not correlate
with any particular cytogenetic abnormality nor with LOH.
PMID- 9641221
TI - The effect of fixation on the size, shape and summed optical density of
endometrial cancer nuclei.
AB - OBJECTIVE: Nuclear morphometric features have been shown to be of prognostic
importance in several malignancies including recently, endometrial cancer. The
authors attempted to see whether the type of fixation affected nuclear size
(NUSZ), shape (NUSH), and summed optical density (NUSD). METHODS: Fifty
specimens, half air dried and half alcohol fixed, were obtained from 25
consecutive patients with endometrial cancer. Results were compared with the
paired samples t-test. Differences among the nuclear morphometric features and
histologic grade, stage, and depth of myometrial invasion were studied by one-way
analysis of variance. Logistic regression was used to determine if any were
independent prognostic features. Image analysis was used to determine NUSZ, NUSH,
and NUSD. RESULTS: Mean NUSZ was shown to be significantly larger in air dried
specimens (89.13 microm2) as compared to alcohol fixed specimens (80.34 microm2)
P=0.047. Mean NUSH was significantly closer to round in air dried specimens
(15.21) as compared to alcohol fixed specimens (15.65) P=0.025. There was no
significant difference in mean NUSD between air dried (128.61) and alcohol fixed
specimens (126.22) P=0.76. Stage, as well as air dried NUSZ, NUSH, and NUSD were
all independent predictors of recurrence. In this study none of the nuclear
parameters from the alcohol fixed tissues were predictive of recurrence.
CONCLUSION: The type of fixation significantly affects the nuclear morphometric
parameters of size and shape. While NUSZ, NUSH, and NUSD from air dried specimens
were predictive of recurrence, the same parameters from alcohol fixed specimens
were not. A larger prospective trial is currently underway to validate these
findings.
PMID- 9641222
TI - Well-differentiated versus less-differentiated endometrial carcinoma.
AB - The aim of this study was to compare well-differentiated (grade 1) and less
differentiated (grades 2 and 3) endometrial carcinoma, concerning clinical risk
factors, presenting symptoms and operative findings. Seventy-one surgically
staged endometrial carcinoma cases were reviewed and retrospectively divided
according to tumor differentiation into two groups: grade 1 cases (Group I; n=40)
and grade 2 and 3 cases (Group II; n=31). No difference was found between the two
groups when comparing patient age, gravidity and parity, history of hypertension,
diabetes or other malignancies, duration of menopause, number of patients
receiving hormonal replacement therapy and histological type of tumor. There was
also no difference in presenting symptoms or in duration of uterine bleeding up
to the diagnosis of endometrial carcinoma. On the other hand, patients with well
differentiated tumors, as compared to patients with less-differentiated
endometrial carcinoma, were significantly more obese (p<0.02), had a smaller
uterus (p<0.01) and presented with less advanced stage disease (p<0.0005). The
fact that the age of the patients, as well as the duration of uterine bleeding
before diagnosis, was similar in both groups may indicate that more advanced
cases, as in group II, represent originally a more aggressive tumor rather than
progression from a well-differentiated disease. This hypothesis needs further
research.
PMID- 9641223
TI - Cavernous haemangioma of the breast. A case report.
PMID- 9641224
TI - Staging nodal growth in breast cancer on a histological basis.
AB - This study describes the axillary tumour-load in 484 women with breast carcinoma
with spread to one or more nodes. The aim was to relate tumour-load to nodal
histology. The tumour area and that of residual lymphoid tissue was measured from
standardised nodal sections. The presence/absence of tumor cells in the efferent
vessels (EV) defined their nodal status as EV+ or EV-. The former has a poor
prognosis. While the number of EV+ cases increased with the total tumour-load,
the number of EV- cases decreased. In the EV+ there was high positive correlation
between tumour-load and number of deaths from breast cancer, with a corresponding
negative correlation in the EV-. Twice as many patients with EV+ nodes died of
breast cancer compared to the EV- group. Investigation of 164 consecutive tumour
bearing nodes showed a similar pattern. Irrespective of EV status the area of
residual lymphoid tissue remained constant. Although the lymphoid area was
similar the tumour-load was twice as high in the EV+ cases. These findings stress
basic biological differences in the growth of breast carcinoma in the nodes.
Patients with the smallest micrometastases that are found in the afferent
lymphatics of the node and the EV+ patients in which tumour cells are present in
the efferent nodal vessels have a poor short-term prognosis. The patients with
larger micrometastases in the nodal lymphoid tissue and also EV- patients with
the next highest tumour-load are both of low prognostic risk, with the exception
of the few EV- with an exceptionally high tumour-load.
PMID- 9641225
TI - Management of cervical intraepithelial neoplasia of the uterine cervix: 110 cases
treated by cold-knife conization.
AB - PURPOSE OF INVESTIGATION: The purpose of this study was to evaluate treatment by
cold-knife-conization in women carriers of cervical intraepithelial neoplasia
(CIN). METHODS: The histologic findings of pre-clinical neoplasia of the cervix
after conization were compared to the previous findings of cytology, colposcopy
and punch-biopsy in 110 women examined between 1985 and 1995. The chi square test
(chi2) was used for the statistical analysis. RESULTS AND CONCLUSIONS: A close
correlation is clinically important where complementary roles of these three
methods are used to identify lesions suitable for local ablative therapy. The Pap
test alone is no longer sufficient for the screening of the pre-cancerous lesion
of the cervix and colposcopy is compulsory each time the smear is inadequate or
altered. Conization permitted us to single out 13 (11.8%) cases of carcinoma.
After cold-knife conization we had six (5.4%) recurrences within two years and
two (1.8%) within three years. Our data show that conservative therapy by
conization in women with CIN reduces the risk of invasive cancer of the cervix
but careful follow-up of these patients is essential.
PMID- 9641226
TI - Primary sarcoma of the ovary: report of five cases and review of the literature.
AB - Primary ovarian sarcomas are rare and usually behave very aggressively. Over a
ten-year period (1987-1996) five cases of primary ovarian sarcoma were managed at
the Soroka Medical Center, Beer-Sheva, Israel. Four patients had malignant
mullerian-mixed mesodermal tumor (MMMMT): two had Stage IIIC tumor with
chondrosarcoma being the predominant sarcomatous element, one had Stage IIIC
tumor with high-grade endometrioid stromal sarcoma (ESS) being the predominant
sarcomatous element and one had Stage IC tumor with rhabdomyosarcoma being the
predominant sarcomatous element. One patient had Stage IA leiomyosarcoma (LMS).
All four patients with MMMMT received postoperative adjuvant chemotherapy,
whereas the patient with LMS did not. The four patients with MMMMT died of their
disease 10, 10, 13 and 25 months, respectively, after initial surgery. The
patient with LMS died of intercurrent disease 21 months after initial surgery. It
is concluded that most patients with primary ovarian sarcoma present with
extraovarian disease and the prognosis is poor. The mainstay of treatment is
debulking surgery consisting of total abdominal hysterectomy, bilateral salpingo
oophorectomy and extirpation of tumor masses. The benefit of postoperative
adjuvant chemotherapy and/or radiotherapy is still a subject of debate and has
yet not been established.
PMID- 9641227
TI - Angiogenic activity and interleukin-8 content of human ovarian cancer ascites.
PMID- 9641228
TI - Intraperitoneal cisplatin-mitoxantrone and intravenous ifosfamide combination as
first-line treatment of ovarian cancer.
AB - Twenty-one chemotherapy naive ovarian cancer patients with stage III and minimal
residual tumor were treated with cisplatin 75 mg/m2 and mitoxantrone 15 mg/m2
(1st day) by intraperitoneal (i.p.) route and ifosfamide 4 g/m2 (15th day) by
i.v. route every 4 weeks for a total of 6 cycles. Pathologic complete response
(pCR) was achieved in 9/20 (45%, 95% Confidence Interval - CI - 23-68) of the
patients. The median progression free interval (PFI) of the patients with pCR was
45 (range: 18-70) months. For patients with residual tumor <1 cm (n: 11); pCR was
82% and could be achieved only in this subgroup of patients. The cumulative (PFI)
and overall survival rate of all patients at 3 years were 40% and 52%,
respectively. The median PFI was found to be significantly different between the
patients with residual tumor <1 cm (48 months, 95% CI 42-54) and 1-2 cm (9
months, 95% CI 1-16) p<0.001. Main toxicities were emesis and abdominal pain
which occurred in 53% and 65% of the courses, respectively. This combination
seems to be an effective and feasible approach to previously untreated ovarian
cancer patients with minimal tumor burden.
PMID- 9641229
TI - Leiomyosarcomas of the small intestine misdiagnosed as ovarian masses: report of
three cases.
AB - Leiomyosarcomas of the small intestine are rare lesions. Because of their
aspecific symptoms, diagnosis is often made at a late stage and, in women, must
be distinguished from ovarian tumors. Three cases of large, abdominal masses,
evaluated preoperatively as being ovarian tumors, are presented. At histology all
three were diagnosed as leiomyosarcomas of the small intestine.
PMID- 9641230
TI - Catheter complications associated with intraperitoneal chemotherapy.
AB - Catheter complications associated with intraperitoneal chemotherapy were
evaluated in 171 patients (pts) with primary intra-abdominal malignancies. In 96
pts and 488 courses, single-use catheters (SUC) (3/G 14 Braun) were used between
years 1990-1993. In 75 pts and 283 courses a semi-permanent subcutaneous
implantable port and catheter system (SIPC) (T 2035/460 mm-F 14-76 Braun) was
used between years 1993-1996. Cisplatin (60-75 mg/sqm), 5-fluorouracil (600
mg/sqm), calcium folinate (150 mg), etoposide (180 mg/sqm), mitoxantrone (12-15
mg/sqm) were given in various combinations and periods to patients with ovarian
carcinoma (106 pts), gastrointestinal carcinoma (43 pts), hepatocellular
carcinoma (17 pts) and mesothelioma (5 pts). The incidence of patients with
complications was significantly higher in SUC (45%) than SIPC (23%) (p=0.001).
Colon puncture (8.8%, p<0.0001) and subcutaneous leakage (3.7%, p<0.01) rate of
the courses were significantly higher in SUC. Pain related to catheter
complications (6%, p<0,0002), local infection (1.4%, p=0.02) and obstruction
(1.4%, p=0.02) were significantly higher in SIPC. The most important local
complications were intra-abdominal fibrosis and adhesions that were surgically
documented in 90% of the ovarian cancer patients, and were more severe in
patients with the SIPC system. The complication rate and the complication type of
these two catheters were found to be significantly different in this
retrospective analysis; in order to determine the real complication rate, safety,
efficacy and overall acceptability of the catheters, a randomised trial is
needed.
PMID- 9641231
TI - A second primary malignancy in a cohort of patients with epithelial ovarian
cancer--characteristics of diagnosis.
AB - As the life expectancy of cancer patients has been extended because of earlier
diagnosis and improved therapeutic modalities, second primary tumors are being
diagnosed more frequently. We have examined the clinical characteristics of 38
second primary tumors in a cohort of patients diagnosed with epithelial ovarian
cancer in our department over a 6-year period. The most frequent neoplasm
associations were in decreasing order of occurrence: ovary-breast, ovary
endometrium, and ovary-gastro-intestinal tract. Most heterochronous second
primary tumors have been diagnosed following patient symptoms and not during
routine follow-up of patients with a known primary cancer. Family history was
obtained for 30/38 patients (19 with full pedigrees and 11 with partial
information). Two of these 30 patients (6.6%) had one affected first degree
relative-one with ovarian cancer and one with breast cancer. With an increased
risk of developing a second malignancy after having a previous tumor, closer
surveillance of patients posttreatment for cancer is warranted.
PMID- 9641232
TI - Primary pure choriocarcinoma of the ovary in reproductive ages: a case report.
AB - Choriocarcinoma is an aggressive tumor with cyto- and syncytiotrophoblastic
cells. It arises gestationally or nongestationally. Nongestational
choriocarcinoma of the ovary can be pure or mixed with other germ cell tumors.
Pure type is less frequent than mixed type and the diagnosis of nongestational
choriocarcinoma of the ovary is very difficult in the reproductive period. A case
of a 20-year-old woman with pure choriocarcinoma of the ovary is presented with a
review of the literature and discussion of its origin.
PMID- 9641233
TI - Stress and cervical dysplasia.
AB - The aim of the study was to evaluate the relationship between personality, stress
and cervical dysplasia. Twenty women with cervical dysplasia were compared to a
control group of 23 healthy women. An evaluation of their personality was made by
the 16 PF questionnaire; stressing events were investigated with the Paykel
scale; hormonal repercussions were studied by using serum and urinary cortisol
titers. Significant differences were found in intellectual capability and
fancifulness, as well as in cortisol levels. Considering the significant issues
that have emerged, we feel that this research is worthy of further investigation
and that new evaluation parameters are necessary.
PMID- 9641234
TI - Mucoepidermoid carcinoma of the breast.
AB - Mucoepidermoid carcinomas are very rare breast tumors. The morphology of this
breast tumour is similar to its counterpart in the salivary gland. The first two
cases reported were low-grade and neither patient had metastatic disease.
Furthermore, none of the five patients with low-grade mucoepidermoid carcinoma
reported by Fisher had axillary lymph node involvement and were alive with no
evidence of disease 4 to 10 years after diagnosis and were considered of probable
favourable prognosis. A high grade form of mucoepidermoid cancer might occur in
the breast as it does in the salivary gland. All high-grade variant cases
published had demonstrable lymph node or distant metastases and rapidly fatal
outcomes. This report describes a case of high-grade mucoepidermoid carcinoma of
the breast with a disease-free interval of 5 years, despite of unfavourable
histologic features at the time of diagnosis.
PMID- 9641235
TI - A comparison of laparoscopic surgery with open procedure in endometrial cancer.
AB - BACKGROUND: Laparoscopic hysterectomy and lymph node dissection have lately been
reported as an alternative to an abdominal open procedure for the treatment of
malignant gynaecological conditions. The laparoscopic operative technique has
been evaluated and compared as to whether it is a safe, feasible and effective
procedure. SUBJECTS: The study includes 78 women with indications for surgery for
endometrial cancer stage I. A retrospective comparative study was undertaken at
Baby Friendly Hospital, Kladno, in which 11 patients treated laparoscopically
were compared with 26 patients treated by the open procedure of lymphadenectomy.
We evaluated differences in the peri-and postoperative outcomes. RESULTS: All 11
procedures were successfully completed. The mean operating time was 153 min, and
mean blood loss was 130 ml. The median hospital stay was 4.7 days. There were no
major complications. CONCLUSIONS: Laparoscopic hysterectomy and lymphadenectomy
seem to be the procedures which result in a shorter hospital stay and rapid
recovery. This approach could potentially decrease morbidity historically
associated with hysterectomy and lymphadenectomy performed abdominally. Only
prospective randomised studies will be able to demonstrate the ability of
operative laparoscopy to improve contemporary management of endometrial cancer.
PMID- 9641236
TI - Malignant ovarian tumors: conservative surgery and quality of life in young
patients.
AB - Better knowledge and adequate treatment of malignant ovarian tumors have improved
the quality of life of young women--especially of child-bearing age. Nowadays
preservation of ovarian function in women with tumors in early stage (I) or, in
selected cases even in advanced stage (II-III), must be evaluated for
conservative surgery (sometimes expressly requested by the patient herself). In
our Institute we have followed this philosophy for many years and our experience
confirms its value: 42 patients under age 40 (36 in stage I and 6 in advanced
stage) underwent conservative surgery: 12 subsequently became pregnant and
another 12 are able to conceive. Five- and ten-year survival rates are very good
with 89.2% and 83.3% for all stages and 96.9% and 95% for early stages.
PMID- 9641237
TI - High-risk gestational trophoblastic disease: analysis of clinical prognoses.
AB - PURPOSE OF INVESTIGATION: An attempt to better define factors leading to patient
survival in the high-risk group of malignant gestational trophoblastic disease
(GTD). METHODS: From January 1, 1997 to December 31, 1995 25 cases of malignant
high-risk GTD were retrospectively collected to evaluate prognostic factors by
univariate and multivariate analysis. RESULTS: We identified the presence of
liver metastases and/or brain metastases and the presence of intestinal
metastases as significant by using univariate analysis. However, only the
presence of liver metastases of brain metastases was significant by multivariate
analysis (p=0.009). CONCLUSIONS: Although a high-risk group of GTD can be
identified according to the modified World Health Organization (WHO) prognostic
scoring system, liver metastases were not emphasized (only two points) in this
scoring system. We suggested that these risk factors, including brain metastases
and liver metastases, should be weighted more than other risk factors.
PMID- 9641238
TI - Massive bilateral ovarian edema: report of 2 cases.
AB - PURPOSE OF INVESTIGATION: Diagnostic and therapeutic approaches in two cases of
bilateral massive ovarian edema were evaluated. METHODS: Two cases were
retrospectively evaluated with the help of the medical reports. RESULTS: Both
patients presented with left lower abdominal quadrant pain. Cystic pelvic masses
were detected during abdomino-pelvic examination and confirmed with
transabdominal ultrasonography. There were no abnormal laboratory results.
Explorative laparotomy was performed with the diagnosis of torsion or rupture of
ovarian tumor. Bilateral wedge resection with subsequent frozen section was
performed. The final pathology was reported as bilateral massive ovarian edema.
CONCLUSION: A diagnostic bilateral wedge resection with subsequent frozen section
is essential in the management and confirmation of the diagnosis. As the vast
majority of the cases are young, a conservative surgical management is mandatory
to preserve ovarian function.
PMID- 9641239
TI - Expression of ras p21 in the stromal cells of human neoplastic endometrium.
AB - ras p21 proteins have been reported to take part in signal transduction through a
cell membrane to the nucleus and they also play a crucial role in the process of
carcinogenesis. Forty specimens of neoplastic endometrium, ten slides of normal
endometrium and one case of uterine carcinosarcoma were investigated for ras p21
expression in the stromal cells by immunohistochemistry. Stromal cells expressed
ras p21 protein in 13 out of 40 (33%) cases of neoplastic endometrium. These
cells were randomly dispersed wound the glandular crypts of the endometrium and
were also detected in the adjacent myometrium surrounding the cancer tissue. When
cancers were grouped by surgical stage, ras p21 protein was detected in 11/22
(50%) of stage I, but only in 2/18 (11%) of stages II-IV according to FIGO. None
of the stromal cells immunostained for p21 in normal endometrium or myometrium,
however, a single case of carcinosarcoma expressed ras p21 within the stromal
cells.
PMID- 9641240
TI - nm23 expression in carcinoma of the uterine cervix.
AB - To evaluate the significance of nm23 protein expression in cervical carcinoma, 83
patients with stage IB disease, treated primarily with surgery were studied
immunohistochemically. Of the cases 57 were squamous carcinoma, 9 were
adenocarcinoma, 14 were adenosquamous carcinoma and 3 were small-cell carcinoma.
nm23 expression was positive in 63% of the cases. Although positive expression
was more common in squamous and adenosquamous type tumors, negative expression
was dominant in adenocarcinoma (P<0.05). When nm23 expression was compared with
the clinicopathologic risk factors, there was no correlation of expression with
the grade, deep invasion of the stroma, parametrial involvement and lymph node
metastasis. But expression was inversely correlated with the number of metastatic
lymph nodes (P<0.05). Although 3 or more lymph node metastases is a very poor
prognostic sign, nm23 expression was not correlated either with recurrence or
survival. Expression was negative in 77% of metastatic lymph nodes and in all of
the recurrences. The predominance of negative expression in metastatic lymph
nodes (P<0.05) and recurrences seems to be related to the aggressive behavior of
the negative clone in the heterogeneous primary tumor.
PMID- 9641241
TI - Abnormal expression of cripto and p53 protein in endometrial carcinoma and its
precursor lesions.
AB - Many oncogenes and tumor suppressor genes are involved in multistep
carcinogenesis. Cripto is an epidermal growth factor (EGF) related gene which
shares homology with EGF and TGFalpha. The aim of this study was to evaluate the
role of abnormal p53 and cripto oncogene expression in endometrial carcinogenesis
and progression using a hyperplasia carcinoma sequence model. Ninety-six primary
endometrial adenocarcinomas and 30 hyperplastic tissues of which 7 were atypical
(AH), were immunohistochemically examined for the presence of cripto and abnormal
p53 protein. Immunopositivity was compared in hyperplastic and carcinoma tissues
and analysed for conventional clinicopathological prognostic variables such as
grade, depth of myometrial invasion, lymphovascular invasion, lymph node
metastases and clinical stage. Cripto immunoreactivity was strong in most cases
of AH, and endometrial carcinomas revealed 71% overall and 41% strong positivity,
while hyperplasias without atypia were weakly stained. There was no correlation
between cripto expression and clinicopathological prognosticators. Abnormal p53
was not observed in hyperplasias but AH and carcinomas expressed 14% and 25%
overall positivity, respectively. There was a statistically significant
correlation between the stage of the disease and abnormal p53 accumulation. Our
results suggest that both cripto and p53 may play a role in endometrial
carcinogenesis while abnormal p53 expression is an important parameter for
disease progression.
PMID- 9641242
TI - Human papilloma virus in verrucus carcinoma of the vulva: an immunopathological
study of three cases.
AB - The pathological features of three cases of verrucus carcinoma of the vulva,
examined in our laboratory during the last decade are presented. Verrucus
carcinoma of the vulva is of special interest because of its rarity (6.5% of our
cases of malignant lesions of the vulva), its special morphology and the problems
in differential diagnosis that are encountered. There is also evidence that there
is an association with HPV infection. We present the pathological features of
three cases of verrucus carcinoma that we studied in the last decade in our
Laboratory among 48 malignant lesions of the vulva. An immunohistochemical
detection of HPV was performed by the streptavidine-viotine method and
classification by in situ hybridization showed the presence of HPV 6/11 in all
cases.
PMID- 9641243
TI - Brain electric microstates and momentary conscious mind states as building blocks
of spontaneous thinking: I. Visual imagery and abstract thoughts.
AB - Prompted reports of recall of spontaneous, conscious experiences were collected
in a no-input, no-task, no-response paradigm (30 random prompts to each of 13
healthy volunteers). The mentation reports were classified into visual imagery
and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was
continuously recorded, viewed as series of momentary spatial distributions (maps)
of the brain electric field and segmented into microstates, i.e. into time
segments characterized by quasi-stable landscapes of potential distribution maps
which showed varying durations in the sub-second range. Microstate segmentation
used a data-driven strategy. Different microstates, i.e. different brain electric
landscapes must have been generated by activity of different neural assemblies
and therefore are hypothesized to constitute different functions. The two types
of reported experiences were associated with significantly different microstates
(mean duration 121 ms) immediately preceding the prompts; these microstates
showed, across subjects, for abstract thought (compared to visual imagery) a
shift of the electric gravity center to the left and a clockwise rotation of the
field axis. Contrariwise, the microstates 2 s before the prompt did not differ
between the two types of experiences. The results support the hypothesis that
different microstates of the brain as recognized in its electric field implement
different conscious, reportable mind states, i.e. different classes (types) of
thoughts (mentations); thus, the microstates might be candidates for the 'atoms
of thought'.
PMID- 9641244
TI - The effect of attentional load on the breathing pattern in children.
AB - Experiments designed to establish the effects of video games on breathing
patterns have led to contradictory results. Several authors reported that video
games tended to increase breathing frequency (i.e. to reduce breath duration),
whereas others reported the opposite. We postulated that video games contain
different psychophysiological components which may have opposite effects on
breathing pattern. On the one hand, arousal and emotion may tend to stimulate
breathing. On the other, focusing attention on the game may prompt subject to
inhibit any movement--including breathing--which might be a potential nuisance
variable. The aim of this study was to assess the specific effects of the
attentional load in an experimental environment characterized by its low
emotional impact. We measured breathing variables, cardiac frequency and cortisol
levels in 10 healthy children (mean age = 9.2 +/- 1.5 years) who were familiar
with the environment, the experimenter and the video game. Breath duration rose
significantly, from 2.56 to 3.16 s, as a function of game difficulty. Cortisol
levels, heart rate and the thoracic contribution to breathing displayed no
significant changes. Taken together, these data suggest that focusing attention
on the game tended to inhibit breathing and that previous contradictory reports
in this respect were due to the confounding effects of emotion.
PMID- 9641245
TI - Facial and emotional reactions to Duchenne and non-Duchenne smiles.
AB - The purpose of the study was to investigate facial and emotional reactions while
viewing two different types of smiles and the relation of emotional empathy to
these reactions. Facial EMG was recorded from the orbicularis oculi and
zygomaticus major muscle regions while subjects individually watched two blocks
of stimuli. One block included posed facial expressions of the Duchenne smile (a
felt smile) and a neutral face, the other block included expressions of another
type of smile called non-Duchenne smile (an unfelt smile) and a neutral face.
Emotional experiences were asked after each stimulus block. Finally, a measure of
empathy was given. Facial EMG reactions differentiated between the neutral face
and the Duchenne smile but not between the neutral face and the non-Duchenne
smile. The Duchenne smile block induced experience of pleasure for the subjects
who saw it as the first stimulus block. Empathy was correlated to the rated
experiences of pleasure and interest after the Duchenne smile block.
PMID- 9641246
TI - Fingertip temperature as an indicator for sympathetic responses.
AB - Changes of acral skin blood flow are a commonly used indicator for sympathetic
reflex responses to various stimuli. The goal of the present study was to
determine whether decreases in fingertip temperature are indicative for
sympathetic induced changes in microcirculation. Infrared thermography
demonstrated that various stimuli triggering the sympathetic nervous system
induced decreases in cutaneous microcirculation, most prominently in fingertip
skin. Various such stimuli induced almost immediate temporary vasoconstriction,
measured by laser Doppler flux and photoplethysmography. With a lag phase of
approximately 15 s, reduced microcirculation was also reflected by a transient
decrease in fingertip temperature. Vasoconstrictions were easily demonstrable by
fingertip temperature when the starting fingertip temperature was above 32
degrees C and vasoconstriction lasted at least 5 s. Temperature measurement
offers the advantages of ease and simplicity of performance and analysis,
compared with the more complex analyses of flux and pulse volume.
PMID- 9641247
TI - ERPs, semantic processing and age.
AB - ERPs (N400, LPC and CNV) were elicited in two sets of subjects grouped according
to age (young vs. elderly) using a word-pair category matching paradigm. Each
prime consisted of a Japanese noun (constructed from two to four characters of
the Hiragana) followed by one Chinese character (Kanji) as the target, this
latter representing one of five semantic categories. There were two equally
probable target conditions: match or mismatch. Each target was preceded by a
prime, either belonging to, or not belonging to, the same semantic category. The
subjects were required to respond with a specified button press to the given
target according to the condition. We found RTs to be longer in the elderly
subjects and under the mismatch condition. N400 amplitude was reduced in the
elderly subjects under the mismatch condition and there was no difference between
match and mismatch response, which were similar in amplitude to that under match
condition for the young subjects. In addition, the CNV amplitudes were larger in
the elderly subjects. These results suggested that functional changes in semantic
processing through aging (larger semantic networks and diffuse semantic
activation) were the cause of this N400 reduction, attributing a subsidiary role
to attentional disturbance. We also discuss the importance of taking age-related
changes into consideration in clinical studies.
PMID- 9641248
TI - Differences in heartbeat awareness among males with higher and lower levels of
systolic blood pressure.
AB - Recent empirical findings related to the baroreceptor hypothesis indicate that
elevated heart rate, pulse pressure, and blood pressure may dampen exteroception
and interoception. We thus predicted that persons with elevated systolic blood
pressure would be less able to accurately perceive their heartbeats and profit
from feedback training. This study examined the plausibility of this hypothesis
by exposing 57 male students (11 with elevated SBP levels and 46 with
normotensive SBP levels) to the Whitehead heartbeat perception task with, and
without, feedback training. Results indicated that participants with elevated SBP
levels were more able to accurately perceive their heartbeats prior to, and
after, feedback training. Participants with elevated SBP levels also showed a
significant increase in heartbeat perception accuracy when they were provided
with feedback training while participants with normotensive blood pressure levels
did not show a significant response to feedback training. These findings are
interpreted in terms of the ballistic perception model of cardiac awareness.
PMID- 9641249
TI - Electrophysiological evidence for the typicality effect of human cognitive
categorization.
AB - Event-related brain potentials (ERPs) were recorded from 14 normal subjects
during a category verification task. Stimulus words were selected from 17
semantic categories (e.g. 'vegetables'). Half of the words were typical category
members (e.g. 'carrot', 'spinach') and the other half were atypical (e.g.
'parsley', 'asparagus'). Subjects were required to judge whether each stimulus
belonged to a target category ('vegetables' or 'sports') or a non-target
category. For the non-target category, the typicality effect was neither found in
ERPs nor in reaction times. For the target category, typical words were responded
to more quickly than were atypical words and the ERP amplitudes between a 300-450
ms period were more negative after the atypical words than after the typical
words (typicality effect). These results suggested that typical words of the
target were more primed by a target category than were the atypical words of the
target and thus that a concept is represented by a prototype, the central
tendency of all members of the category.
PMID- 9641250
TI - Effects of a negative visual hypnotic hallucination on ERPs and reaction times.
AB - The study of changes in ERPs provoked by negative hypnotic hallucinations has
thus far yielded contradictory results. Most previous studies have failed to
separate specific changes in the processing of the hallucinated stimuli from non
specific changes in arousal due to hypnosis. The present study addresses this
issue with the combination of two experimental effects in the task designed to
test the hallucination: the noise-compatibility effect and the Simon effect. A
choice reaction task was used in which targets appearing at either side of a
screen were defined by color and were accompanied by irrelevant noise, and a
negative hallucination suggestion was given for noise stimuli. Four highly
hypnotizable subjects performed the task on two separate occasions, with and
without the suggestion. Increases in reaction times and P300 latencies were found
as a function of noise and spatial stimulus-response (SR) incompatibility (Simon
effect). Suggestion decreased the response times for all types of trials non
significantly, and it decreased significantly those of left-hand responses. On
the other hand, suggestion reduced the increase in P300 latencies in noise
incompatible trials, but did not influence the Simon effect. This result
indicates a specific effect of suggestion in the processing of hallucinated
stimuli, which is consistent with the hallucinatory experience reported by the
subjects.
PMID- 9641251
TI - A spatio-temporal analysis of recognition-related event-related brain potentials.
AB - Words correctly recognized as previously studied (i.e. old) elicit greater
amounts of positive event-related brain potential (ERP) activity over posterior
scalp between 400 and 800 ms than do previously unstudied (i.e. new) words. While
investigators have reported that this old/new effect consists of more than one
subcomponent, the spatio-temporal parameters of these possible subcomponents, as
well as any other patterns of brain activity associated with recognition, remain
incompletely specified. Thus, ERPs were recorded from 32 scalp sites while 13
subjects performed four repetitions of a study-test recognition paradigm. The
subjects' task was to decide whether each word was old or new and press the
appropriate button as quickly as possible. The timing and topography of the ERPs
elicited by old and new words was assessed with topographic profile comparisons
on the areas with a variety of temporal windows, and visualized with potential
and CSD maps. The results revealed that seven patterns of ERP activity,
dissociable on the basis of their topography, timing and response to experimental
variables, were elicited between 300 and 2000 ms. Three of these appeared as
subcomponents of the old/new effect (maximal over left medial frontal, left
parietal-occipital and right central-frontal scalp), another was related to
decision confidence and/or memory trace strength (maximal over left central
scalp) and three others appeared to be related to more general aspects of
recognition (maximal over the frontal poles, midline frontal scalp and right
frontal scalp). Taken together, the seven distinct patterns of neural generator
activity described here support the hypothesis that retrieval of information from
episodic memory depends on a collection of different processes that occur in a
temporally and spatially distributed neural circuit.
PMID- 9641252
TI - Structure-activity relationships for antioxidant activities of a series of
flavonoids in a liposomal system.
AB - Structurally diverse plant phenolics were examined for their abilities to inhibit
lipid peroxidation induced either by Fe(II) and Fe(III) metal ions or by azo
derived peroxyl radicals in a liposomal membrane system. The antioxidant
abilities of flavonoids were compared with those of coumarin and tert
butylhydroquinone (TBHQ). The antioxidant efficacies of these compounds were
evaluated on the basis of their abilities to inhibit the fluorescence intensity
decay of an extrinsic probe, 3-(p-(6-phenyl)-I,3,5-hexatrienyl)phenylpropionic
acid (DPH-PA), caused by the free radicals generated during lipid peroxidation.
All the flavonoids tested exhibited higher antioxidant efficacies against metal
ion-induced peroxidations than peroxyl-radical-induced peroxidation, suggesting
that metal chelation may play a larger role in determining the antioxidant
activities of these compounds than has previously been believed. Distinct
structure-activity relationships were also revealed for the antioxidant abilities
of the flavonoids. Presence of hydroxyl substituents on the flavonoid nucleus
enhanced activity, whereas substitution by methoxy groups diminished antioxidant
activity. Substitution patterns on the B-ring especially affected antioxidant
potencies of the flavonoids. In cases where the B-ring could not contribute to
the antioxidant activities of flavonoids, hydroxyl substituents in an catechol
structure on the A-ring were able to compensate and become a larger determinant
of flavonoid antioxidant activity.
PMID- 9641253
TI - Clarification of the relationship between free radical spin trapping and carbon
tetrachloride metabolism in microsomal systems.
AB - It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl
radical adduct (PBN/.CCl3) is metabolized to either the C-phenyl-N-tert
butylnitrone/carbon dioxide anion radical adduct (PBN/.CO2-) or the glutathione
(GSH) and CCl4-dependent PBN radical adduct (PBN/[GSH-.CCl3]). Inclusion of
PBN/.CCl3 in microsomal incubations containing GSH, nicotinamide adenine
dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin
resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH
.CCl3] or PBN/.CO2- radical adducts. Microsomes alone or with GSH had no effect
on the PBN/.CCl3 radical adduct. Addition of NADPH to a microsomal system
containing PBN/.CCl3 presumably reduced the radical adduct to its ESR-silent
hydroxylamine because no ESR signal was observed. The Folch extract of this
system produced an ESR spectrum that was a composite of two radicals, one of
which had hyperfine coupling constants identical to those of PBN/.CCl3. We
conclude that PBN/.CCl3 is not metabolized into either PBN/[GSH-.CCl3] or
PBN/.CO2- in microsomal systems.
PMID- 9641254
TI - Dose- and wavelength-dependent oxidation of crystallins by UV light--selective
recognition and degradation by the 20S proteasome.
AB - The lens of the human eye is a suitable model for age-related alterations at the
molecular level. Age-related cataract formation is closely related to the
accumulation of oxidatively altered proteins. In this study the influence of UV
A, UV-B, and UV-C irradiation on the proteolytic susceptibility of alpha-, betaL
, and betaH-crystallins by the isolated 20S proteasome was investigated. The
proteins were irradiated with 280, 300, and 350 nm monochromatic light. Changes
of the physical properties of the crystallins were characterized by absorbance
measurements at 280 nm, fluorescence spectra, and SDS-PAGE-electrophoresis. The
proteolytic susceptibility of crystallins was maximal after irradiation at 280 nm
and three- to fivefold lower at 300 nm. Irradiation at 350 nm was not able to
initiate proteolysis, probably due to protein-aggregate formation of higher
molecular weight, as shown by SDS-PAGE. The damage of crystallins by UV-C light
might be a signal for its proteolytic degradation by the 20S proteasome, whereas
UV-B and UV-A do not increase the proteolytic susceptibility to the same extent
but promote the formation of crosslinked proteins. Therefore, irradiation with
UV, which is not followed by an increase in the proteolytic susceptibility, is
accompanied by the formation of crosslinked proteins. It was concluded, that also
long UV-B and UV-A may be involved in age-related alterations of the human lens
and cataract formation.
PMID- 9641255
TI - Cellular mechanisms of resistance to chronic oxidative stress.
AB - Oxidative stress is implicated in several pathologies such as AIDS, Alzheimer's
disease, and Parkinson's disease, as well as in normal aging. As a model system
to study the response of cells to oxidative insults, glutamate toxicity on a
mouse nerve cell line, HT-22, was examined. Glutamate exposure kills HT-22 via a
nonreceptor-mediated oxidative pathway by blocking cystine uptake and causing
depletion of intracellular glutathione (GSH), leading to the accumulation of
reactive oxygen species and, ultimately, apoptotic cell death. Several HT-22
subclones that are 10-fold resistant to exogenous glutamate were isolated and the
mechanisms involved in resistance characterized. The expression levels of neither
heat shock proteins nor apoptosis-related proteins are changed in the resistant
cells. In contrast, the antioxidant enzyme catalase, but not glutathione
peroxidase nor superoxide dismutase, is more highly expressed in the resistant
than in the parental cells. In addition, the resistant cells have enhanced rates
of GSH regeneration due to higher activities of the GSH metabolic enzymes gamma
glutamylcysteine synthetase and GSH reductase, and GSH S-transferases activities
are also elevated. As a consequence of these alterations, the glutamate resistant
cells are also more resistant to organic hydroperoxides and anticancer drugs that
affect these GSH enzymes. These results indicate that resistance to apoptotic
oxidative stress may be acquired by coordinated changes in multiple antioxidant
pathways.
PMID- 9641256
TI - Involvement of oxidative stress in paraquat-induced metallothionein synthesis
under glutathione depletion.
AB - The inhibition of glutathione (GSH) synthesis by L-buthionine-SR-sulfoximine
(BSO) causes aggravation of hepatotoxicity of paraquat (PQ), an oxidative-stress
inducing substance, in mice. On the other hand, synthesis of metallothionein
(MT), a cysteine-rich protein having radical scavenging activity, is induced by
PQ, and the induction by PQ is significantly enhanced by pretreatment of mice
with BSO. The purpose of present study is to examine whether generation of
reactive oxygens is involved in the induction of MT synthesis by PQ under
inhibition of GSH synthesis. Administration of PQ to BSO-pretreated mice
increased hepatic lipid peroxidation and frequency of DNA single strand breakage
followed by manifestation of the liver injury and induction of MT synthesis. Both
vitamin E and deferoxamine prevented MT induction as well as lipid peroxidation
in the liver of mice caused by administration of BSO and PQ. In cultured colon 26
cells, both cytotoxicity and the increase in MT mRNA level caused by PQ were
significantly enhanced by pretreatment with BSO. Facilitation of PQ-induced
reactive oxygen generation was also observed by BSO treatment. These results
suggest that reactive oxygens generated by PQ under inhibition of GSH synthesis
may stimulate MT synthesis. GSH depletion markedly increased reactive oxygen
generation induced by PQ, probably due to the reduced cellular capability to
remove the radical species produced.
PMID- 9641257
TI - Degradation of hyaluronic acid, poly- and monosaccharides, and model compounds by
hypochlorite: evidence for radical intermediates and fragmentation.
AB - Degradation of hyaluronic acid by oxidants such as HO. and HOCl/CIO- is believed
to be important in the progression of rheumatoid arthritis. While reaction of
hyaluronic acid with HO. has been investigated extensively, reaction with
HOCl/ClO- is less well defined. Thus, little is known about the site(s) of
HOCl/ClO- attack, the intermediates formed, or the mechanism(s) of polymer
degradation. In this study reaction of HOCl/ClO- with amides, sugars,
polysaccharides, and hyaluronic acid has been monitored by UV-visible (220-340
nm) and EPR spectroscopy. UV-visible experiments have shown that HOCl/ClO- reacts
preferentially with N-acetyl groups. This reaction is believed to give rise to
transient chloramide (R-NCl-C(O)-R') species, which decompose rapidly to give
radicals via either homolysis (to produce N. and Cl.) or heterolysis (one
electron reduction, to give N. and Cl.) of the N--C bond. The nature of the
radicals formed has been investigated by EPR spin trapping. Reaction of HOCl/ClO-
with hyaluronic acid, chondroitin sulphates A and C, N-acetyl sugars, and amides
gave novel, carbon-centered, spin adducts, the formation of which is consistent
with selective initial attack at the N-acetyl group. Thus, reaction with
hyaluronic acid and chondroitin sulphate A, appears to be localized at the N
acetylglucosamine sugar rings. These carbon-centered radicals are suggested to
arise from rapid rearrangement of initial nitrogen-centered radicals, formed from
the N-acetyl chloramide, by reactions analogous to those observed with alkoxyl
radicals. The detection of increasing yields of low-molecular-weight radical
adducts from hyaluronic acid and chondroitin sulphate A with increasing HOCl/ClO
concentrations suggests that formation of the initial nitrogen-centered species
on the N-acetylglucosamine rings, and the carbon-centered radicals derived from
them, brings about polymer fragmentation.
PMID- 9641258
TI - Functional activity of blood polymorphonuclear leukocytes as an oxidative stress
biomarker in human subjects.
AB - In the present work, we studied the role of polymorphonuclear leukocytes (PMN) in
aged individuals and coronary heart disease (CHD)-bearing patients, two
physiopathological processes associated with overproduction of reactive oxygen
species (ROS). The effects of antioxidant supplementation on the functional
activity of PMN from CHD patients were also determined. The function of PMNs was
evaluated by measuring of phagocytosis, killing activity, and ROS production.
Luminol amplified chemiluminescence (CL) was used to estimate ROS production by
stimulated PMNs. Total cholesterol and the LDL-cholesterol fraction from CHD
patients were found to be higher than those recommended, returning to normal
levels after antioxidant therapy. PMN CL of CHD patients was found to be higher
than the associated control groups. Antioxidant therapy administrated to CHD
patients lead to an increase in the killing activity accompanied by a decrease in
PMN CL of these subjects. The study also showed that killing activity of PMN from
human subjects over 60 years was significantly lower than the activity measured
in younger subjects. PMN CL produced after stimulation was found to be positively
correlated with the increasing age of human subjects (r=.946, p < .01).
PMID- 9641259
TI - Structural aspects of the inhibitory effect of glabridin on LDL oxidation.
AB - The inhibitory effects of glabridin, an isoflavan isolated from licorice
(Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by
copper ions or mediated by macrophages were studied, in order to evaluate the
contribution of the different parts of the isoflavan molecule to its antioxidant
activity. The peak potential (E1/2) of the isoflavan derivatives, their radical
scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and
their ability to chelate heavy metals were also analyzed and compared to their
inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation,
glabridin (1), 4'-O-methylglabridin (2), hispaglabridin A (3), and hispaglabridin
B (4), which have two hydroxyl groups at positions 2' and 4' or one hydroxyl at
position 2' on ring B, successfully inhibited the formation of conjugated dienes,
thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and
inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1-3
exhibited similar activities, whereas compound 4 was less active. In macrophage
mediated LDL oxidation, the TBARS formation was also inhibited by these
isoflavans (1-4) at a similar order of activity to that obtained in copper ion
induced LDL oxidation. On the other hand, 2'-O-methylglabridin (5), a synthesized
compound, whose hydroxyl at 2'-position is protected and the hydroxyl at 4'
position is free, showed only minor inhibitory activity in both LDL oxidation
systems. 2',4'-O-Dimethylglabridin (6), whose hydroxyls at 2'- and 4'-positions
are both protected, was inactive. Resorcinol (7), which is identical to the
phenolic B ring in glabridin, presented low activity in these oxidation systems.
The isoflavene glabrene (8), which contains an additional double bond in the
heterocyclic C ring, was the most active compound of the flavonoid derivatives
tested in both oxidation systems. The peak potential of compounds 1-5 (300
microM), tested at pH 7.4, was similar (425-530 mV), and that for compound 6 and
8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2,
3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas
compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to
scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were
able to chelate iron, or copper ions. These results suggest that the antioxidant
effect of glabridin on LDL oxidation appears to reside mainly in the 2' hydroxyl,
and that the hydrophobic moiety of the isoflavan is essential to obtain this
effect. It was also shown that the position of the hydroxyl group at B ring
significantly affected the inhibitory efficiency of the isoflavan derivatives on
LDL oxidation, but did not influence their ability to donate an electron to DPPH
or their peak potential values.
PMID- 9641260
TI - Effect of the peroxisome proliferator ciprofibrate on lipid peroxidation and 8
hydroxydeoxyguanosine formation in transgenic mice with elevated hepatic catalase
activity.
AB - Peroxisome proliferators are a group of non-genotoxic hepatic carcinogens which
have been proposed to act by increasing oxidative damage in the liver. To test
this hypothesis, we have produced a transgenic mouse line that has elevated
catalase activity specifically in the liver. In this study, we have examined if
catalase overexpression influences the induction of lipid peroxidation or
oxidative DNA damage, two mechanisms which have been hypothesized to be important
in the carcinogenesis by peroxisome proliferators. Transgenic mice or non
transgenic litter mates were fed either 0.01% ciprofibrate or a control diet for
21 days. The activities of fatty acyl CoA oxidase and lauric acid hydroxylase
were not significantly affected by catalase overexpression, although the ratio of
fatty acyl CoA oxidase to catalase was significantly decreased in transgenic
animals. Hepatic lipid peroxidation was estimated by quantifying the
concentrations of malondialdehyde and conjugated dienes. Ciprofibrate treatment
did not affect either endpoint, but catalase overexpression increased the
concentrations of malondialdehyde (in untreated mice only) and conjugated dienes
(in both untreated and ciprofibrate-fed mice). Oxidative DNA damage was estimated
by quantifying 8-hydroxydeoxyguanosine (8-OHdG) by high-performance liquid
chromatography/electrochemical detection. Ciprofibrate treatment significantly
increased hepatic 8-OHdG concentrations, in agreement with several previous
studies, but catalase overexpression did not significantly affect them, although
8-OHdG concentrations were decreased 50% in untreated mice. These results imply
that the metabolism of hydrogen peroxide by catalase is not an important factor
in the development of hepatic lipid peroxidation. The decrease in hepatic 8-OHdG
in untreated transgenic mice and the increase seen after ciprofibrate
administration imply that hydrogen peroxide is important in the formation of 8
OHdG. While the lack of decreased 8-OHdG levels in ciprofibrate-treated
transgenic mice does not support this conclusion, it is possible that catalase
levels were not sufficiently high to affect this endpoint. Transgenic mice with
higher hepatic catalase activities may be required to resolve this issue.
PMID- 9641261
TI - Cytotoxicity-associated effects of reactive oxygen species on endothelin-1
secretion by pulmonary endothelial cells.
AB - In this study bovine pulmonary artery endothelial cells (BPAEC) were used as a
model system to investigate the effects of the hypoxanthine-xanthine oxidase
(HXXO) oxygen radical donor system on ET-1 secretion into pulmonary vasculature.
Incubation of BPAEC with HXXO for 4 h caused a significant reduction in ET-1
secretion, which was significantly offset by allopurinol or catalase, but not by
Cu/Zn superoxide dismutase (SOD). ET-1 secretion was also reduced by H2O2, and
this effect was again significantly offset by catalase. XO alone also reduced ET
1 secretion, but to a significantly lesser degree than did HXXO, and this effect
was not offset by allopurinol, catalase, or SOD. None of the oxidant treatments
were associated with a loss of immunoreactive ET-1 from endothelial cell medium
containing synthetic peptide. The HXXO- and H2O2-mediated reductions in ET-1
secretion were accompanied by evidence of reduced cell viability. This loss of
viability was absent when cells were treated with HXXO + catalase, allopurinol,
or mercaptopropionyl glycine, but not when SOD was present. We conclude that
under conditions of oxidative stress, the pulmonary vascular endothelium responds
by secreting less ET-1. This may be relevant to its vasodilator functions in the
pulmonary vasculature, which would therefore be compromised when the endothelium
is exposed to oxidant stress.
PMID- 9641262
TI - Interleukin-1 expression during hyperoxic lung injury in the mouse.
AB - An important component of the pathophysiologic response to hyperoxia (O2) is
pulmonary inflammation, although the roles of specific inflammatory mediators
during pulmonary O2 toxicity are not completely known. Interleukin-1 (IL-1) is an
early inflammatory mediator and is sufficient to elicit many of the responses
associated with acute injury. The IL-1 family comprises two bioactive proteins,
IL-1alpha and IL-1beta, and their natural antagonist IL-1ra. Here we report
studies of IL-1 regulation during hyperoxic lung injury in the adult mouse. When
assayed by Northern blot, increases in IL-1beta mRNA were seen after 2 days of
hyperoxia. In contrast, IL-1alpha mRNA was barely detectable before 4 days of
hyperoxia. To further understand the cellular origin of IL-1beta expression in
lungs, in situ hybridization and immunohistochemical analyses were performed. IL
1beta mRNA or protein was not detected in the lungs of unexposed animals. At 3
days, we observed the accumulation of IL-1beta transcripts in pulmonary
interstitial macrophages and in a subset of neutrophils, and immunodetectable IL
1beta protein was co-localized in adjacent sections. At 4 days of exposure, IL
1beta transcripts were widespread in lung tissue, but many areas rich in IL-1beta
mRNA were devoid of immunodetectable IL-1beta. However, it is not known whether
increased synthesis of IL-1beta or the uncoupling of IL-1beta protein and mRNA
accumulation has a role in pathophysiology of pulmonary O2 toxicity.
PMID- 9641263
TI - Effect of naturally occurring flavonoids on lipid peroxidation and membrane
permeability transition in mitochondria.
AB - The ability of eight structurally related naturally occurring flavonoids in
inhibiting lipid peroxidation and mitochondrial membrane permeability transition
(MMPT), as well as respiration and protein sulfhydryl oxidation in rat liver
mitochondria, was evaluated. The flavonoids tested exhibited the following order
of potency to inhibit ADP/ Fe(II)-induced lipid peroxidation, estimated with the
thiobarbituric acid assay: 3'-O-methyl-quercetin > quercetin > 3,5,7,3',4'-penta
O-methyl-quercetin > 3,7,3',4'-tetra-O-methyl-quercetin > pinobanksin > 7-O
methyl-pinocembrin > pinocembrin > 3-O-acyl-pinobanksin. MMPT was estimated by
the extent of mitochondrial swelling induced by 10 microM CaCl2 plus 1.5 mM
inorganic phosphate or 30 microM mefenamic acid. The most potent inhibitors of
MMPT were quercetin, 7-O-methyl-pinocembrin, pinocembrin, and 3,5,7,3',4'-penta-O
methyl-quercetin. The first two inhibited in parallel the oxidation of
mitochondrial protein sulfhydryl involved in the MMPT mechanism. The most potent
inhibitors of mitochondrial respiration were 7-O-methyl-pinocembrin, quercetin,
and 3'-O-methyl-quercetin while the most potent uncouplers were pinocembrin and 3
O-acyl-pinobanksin. In contrast 3,7,3',4'-tetra-O-methyl-quercetin and
3,5,7,3',4'-penta-O-methyl-quercetin showed the lowest ability to affect
mitochondrial respiration. We conclude that, in general, the flavonoids tested
are able to inhibit lipid peroxidation on the mitochondrial membrane and/or MMPT.
Multiple methylation of the hydroxyl substitutions, in addition to sustaining
good anti-lipoperoxidant activity, reduces the effect of flavonoids on
mitochondrial respiration, and therefore, increases the pharmacological potential
of these compounds against pathological processes related to oxidative stress.
PMID- 9641264
TI - Effects of a novel, low-molecular weight inhibitor of lipid peroxidation on
ischemia-reperfusion injury in isolated rat hearts and in cultured
cardiomyocytes.
AB - We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of
lipid peroxidation, on cardiac ischemia-reperfusion injury. Lactate dehydrogenase
(LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h
reoxygenation was measured after pretreatment with different concentrations of
H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30
min global ischemia and 60 min reperfusion (n=minimum 10 in each group): 1.
Control ischemia-reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle
during stabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/51
throughout the experiments. During reoxygenation of isolated cardiomyocytes,
H290/51 dose dependently inhibited LD release with an pIC50 value of 7.2+/-0.4
(mean+/-SEM), with 10(-6) mol/l as the lowest efficient concentration. In
isolated hearts ischemia-reperfusion induced severe reperfusion arrhythmias,
reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and
increased LV end-diastolic pressure (LVEDP). LD activity in the effluent
increased. H290/51 throughout perfusion (group 4) reduced the occurrence of
severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p <
.008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD
(p < .002). Tissue contents of thiobarbituric acid-reactive substances did not
increase during reperfusion in controls, but was reduced in group 4 (p < .004).
H290/51 given only during reperfusion (group 3) tended to improve cardiac
function, but significantly so only for increase of CF (p < .01). The lipid
peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia
reperfusion.
PMID- 9641265
TI - Histochemical localization of superoxide dismutase activity in rat brain.
AB - Histochemical localization of superoxide anion (O2.-) scavenging activity in rat
brain was visualized by the tissue-blotting technique. The activity was thought
to mainly depend on Cu/Zn-SOD, because the localization of the activity was
identical with the immunohistochemistry of Cu/Zn-SOD and the localization of its
mRNA in the brain. Moreover, the activity was dramatically decreased after
treatment of Cu (I) chelater. The activity was detected in pyramidal cells of the
cortex, granular, and mitral cells of the olfactory bulbs, pyramidal cell layer
CA1 to CA3, and dentate gyrus of hippocampus formation and granular cells of the
cerebellum. Moreover, the activity was detected in the pontine nuclei of brain
stem. Olfactory bulbs, hippocampus, and cerebellum were believed to be bestowed
high brain functions, i.e., long-term potentiation and long-term depression. A
part of the function was regulated by a retrograde neurotransmitter, nitric oxide
(.NO). Our findings suggest that the SOD is colocalized with NO synthase in
olfactory bulbs, hippocampus, and cerebellum, where .NO plays the important
roles. In contrast, low SOD activity was observed in the axonal neurofiber
bundles, although the regions contain a lot of membrane lipids, which was thought
to be peroxidized by O2.- and related radicals such as .OH in the regions. From
these findings, it was suggested that the SOD did not only play a role in
protecting the neurons from endogenously formed O2.-, but also play a role in
preservation of beneficial natures of .NO in the brain.
PMID- 9641266
TI - Alterations of antioxidant enzymes and oxidative damage to macromolecules in
different organs of rats during aging.
AB - Oxygen free radicals have been hypothesized to play an important role in the
aging process. To investigate the correlation between the oxidative stress and
aging, we have determined the levels of oxidative protein damage and lipid
peroxidation in the brain and liver, and activities of antioxidant enzymes in the
brain, liver, heart, kidney, and serum from the Fisher 344 rats at ages of 1, 6,
12, 18, and 24 months. The results showed that the level of oxidative protein
damage (measured as carbonyl content) in the brain and liver was significantly
higher in older animals than in young animals. No statistical difference was
observed in the lipid peroxidation of the liver and brain between young and old
animals. The activities of antioxidant enzymes in most tissues displayed an age
dependent decline. Superoxide dismutases in the heart, kidney, and serum,
glutathione peroxidase activities in the serum and kidney, and catalase
activities in the brain, liver, and kidney, significantly decreased during aging.
Cytochrome c oxidase, an enzyme involved in electron transport in mitochondria,
initially increased, but subsequently decreased in the aged brain, whereas no
significant alteration was observed in the liver mitochondrial antioxidant
enzymes. The present studies suggest that the accumulation of oxidized proteins
during aging is most likely to be linked with an age-related decline of
antioxidant enzyme activities, whereas lipid peroxidation is less sensitive to
predict the aging process.
PMID- 9641267
TI - Antioxidant defenses influence HIV-1 replication and associated cytopathic
effects.
AB - HIV-infected cells often exhibit reduced levels of antioxidant enzymes and
thiols. To investigate the role of cellular antioxidant defenses in the
progression of an acutely spreading HIV-1 infection, human Sup-T1 T cells were
engineered to overexpress the selenium-dependent glutathione peroxidase, GSHPx-1.
This enzyme represents a major cellular defense mechanism against toxicity
associated with reactive oxygen species (ROS). T cells engineered to produce
elevated GSHPx-1 activity displayed accelerated viral replication and associated
cytopathic effects compared to control cells. Conversely, the inhibition of the
synthesis of glutathione with buthione sulfoximine (BSO) resulted in the
attenuation of viral replication in Sup-T1 cells. Similarly, exposure of human
peripheral blood lymphocytes (PBLs) to low, nontoxic levels of BSO resulted in an
approximately 80% decline in HIV-1 replication as indicated by Western blot
analysis of viral proteins.
PMID- 9641268
TI - Formation of keto and hydroxy compounds of linoleic acid in submitochondrial
particles of bovine heart.
AB - To observe lipid peroxidation of additive-free submitochondrial particles, we
incubated submitochondrial particles in the absence of exogenous irons and t
butyl hydroperoxide. After the incubation, the phospholipids were hydrolyzed by
phopholipase A2, and the fatty acid constituents were analyzed by high
performance liquid chromatography, gas chromatography-mass spectrometry, and
liquid chromatography-mass spectrometry. Contrary to a commonly accepted theory,
lipid peroxidation in the submitochondrial particles did not need the addition of
NADH. In the phospholipid constituent fatty acids of the oxidized
submitochondrial particles, derivatives of hydroperoxides of linoleic acid such
as keto, hydroxy, trihydroxy, and hydroxyepoxy compounds were generated. Lipid
peroxidation in the submitochondrial particles was not inhibited by the addition
of catalase, superoxide dismutase, hydroxyl radical scavengers, or
ethylenediaminetetraacetic acid, but was inhibited by the addition of KCN,
antimycin-A, NADH, ubiquinol, deferoxamine mesylate, ascorbic acid, and alpha
tocopherol. The cardiolipin-cytochrome c lipid peroxidation system could mimic
the lipid peroxidation of the submitochondrial particles, in terms of linoleic
acid products and the inhibitory patterns of radical scavengers and electron
transfer chain inhibitors. Thus, lipid peroxidation in the submitochondrial
particles seems to be due to phospholipid-hemoprotein lipid peroxidation systems
such as the cardiolipin-cytochrome c system.
PMID- 9641269
TI - Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria
infection.
AB - Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2.- into
H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an
indigenous oxidative stress that predisposes them to added insults. In this
study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of
CuZnSOD to determine whether overexpression of CuZnSOD affected the
susceptibility of these mice to plasmodium infection. Acute malaria is associated
with oxidative stress, mediated by redox-active iron released from the infected
RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than
control mice to infection by Plasmodium berghei (P. berghei), reflected by an
earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD
mice were more vulnerable than control mice, the levels of parasitemia were
comparable in both strains. Moreover, treatment of infected red blood cells (RBC)
with oxidative stress inducers, such as ascorbate or paraquat, reduced the
viability of parasites equally in both transgenic and control RBC. This further
confirms that increased CuZnSOD does not support plasmodia development. The data
are consistent with the possibility that the combination of increased redox
active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to
an enhanced Fenton's reaction-mediated HO. production, and the resulting
oxidative injury renders the transgenic mice more vulnerable to parasite
infection.
PMID- 9641270
TI - Nitric oxide in arthritis.
AB - Nitric oxide's (NO) involvement in arthritis was first demonstrated when levels
of nitrite, a stable endproduct of NO metabolism, were shown to be elevated in
serum and synovial fluid samples of rheumatoid and osteoarthritis patients. NO
production by chondrocytes, its involvement in various biochemical events of
cartilage metabolism, and the in vivo suppression of experimental arthritis by NO
synthase inhibitors further implicated NO in arthritis. However, a conclusive
role for NO in the pathogenesis of arthritis remains to be defined, in contrast
to the NO-cGMP signal transduction pathway of endothelium-mediated vasodilation.
It appears that NO has limited modulating effects in cartilage metabolism, with
evidence for both protective and deleterious effects. Recent developments that
contribute to our understanding of NO's role in arthritis are discussed.
PMID- 9641271
TI - Singlet molecular oxygen ((1)O2): a possible effector of eukaryotic gene
expression.
AB - Biological processes involving light may have both beneficial (photosynthesis)
and destructive (photosensitization) consequences. Singlet molecular oxygen,
(1)O2, and other reactive oxygen species such as hydrogen peroxide and hydroxyl
radical, arise during the interaction of light with photosensitizing chemicals in
the presence of molecular oxygen. (1)O2 oxidizes macromolecules such as lipids,
nucleic acids, and protein, depending on its intracellular site of formation; and
promotes detrimental processes such as lipid peroxidation, membrane damage, and
cell death. Photochemical reactive oxygen species (ROS) generating systems induce
the expression of several eukaryotic genes, which include stress proteins, early
response genes, matrix metalloproteinases, immunomodulatory cytokines, and
adhesion molecules. These gene expression phenomena may belong to cellular
defensive mechanisms, or may promote further injury. Whereas the signal
transduction pathways that link site-specific oxidative damage and gene
expression are poorly understood, ROS may affect signalling components in the
membrane, cytosol, or nucleus, leading to changes in phospholipase,
cyclooxygenase, protein kinase, protein phosphatase, and transcription factor
activities. Limited evidence for (1)O2 involvement in gene activation phenomena
consists of deuterium oxide solvent effects, inhibition by (1)O2-quenchers,
sensitization by porphyrins, chemical trapping methods, and comparative effects
of photosensitizing dyes and thermolabile endoperoxides. The studies outlined in
this review support an hypothesis that (1)O2 and other ROS generated during
photochemical processes such as ultraviolet-A (320-380 nm) radiation exposure, or
photosensitizer mediated oxidation may have dramatic effects on eukaryotic gene
expression.
PMID- 9641272
TI - Autocatalytic oxidation of hemoglobin by nitrite: a possible mechanism.
AB - Oxidation of oxyhemoglobin by nitrite ions to produce methemoglobin is one of the
more employed procedures to oxidize the hemoprotein. The process takes place
readily after a clear induction time. This behaviour is usually explained in
terms of an autocatalytic reaction mechanism. However, the generally accepted
mechanism is not autocatalytic and cannot explain the main features of the
process. In the present work it is proposed that the characteristics of the
process require the occurrence of a fast reaction between oxyhemoglobin and
nitrogen dioxide. This process acts as a branching step, leading to the observed
autocatalysis.
PMID- 9641273
TI - Treating recurrence of parotid benign pleomorphic adenomas.
AB - Treatment for recurrence after surgical removal of parotid benign pleomorphic
adenoma (PBPA) has not been well defined and is often followed by further
recurrence. Surgery is overwhelmingly the most common approach. The risk of
facial nerve injury is greater at reoperation since the nerve is less well
defined. The value of radiation therapy (RT) has not been determined and incurs
with it the risk of possible late occurrence of malignancy or nerve damage. The
charts of patients with recurrent PBPA treated consecutively by a single surgeon
from 1965 to 1993 were reviewed. All patients had a histopathologically verified
diagnosis of PBPA both at the time of primary and subsequent surgeries. Follow-up
was obtained from clinical charts and correspondence communication. Recurrence
curves were generated using the Kaplan-Meier method. Thirty-nine patients with
recurrent PBPA (36 referred and 3 treated primarily at Mayo) were evaluated. The
patients were classified according to the type of surgery: 14 patients had
previously undergone some form of parotidectomy or had only resection of the
tumor for recurrence, and 25 patients underwent parotidectomy since this had not
been performed primarily. The mean age in the two groups was 49 and 50 years
respectively. The mean follow-up was 10 years after the recurrence treatment. The
mean time between initial resection and recurrence in the two groups was 14 and
15 years. The mean time between the recurrence treatment and a second recurrence
was 7.5 years. Nine patients had RT in addition to the local resection. Of this
group 3 patients (33%) developed another recurrence. Five patients had local
resection only, and of this group 1 patient (20%) developed another recurrence.
Of the group that had superficial parotidectomy, 3 patients had additional RT and
one of these patients (33%) developed another recurrence. Twenty-two patients had
superficial parotidectomy only, and of this group 3 patients (14%) developed
another recurrence. Only 2 of the 39 patients had complications. One patient
developed Frey's syndrome after superficial parotidectomy and 1 patient developed
facial paralysis after RT. As in other series, the number of patients is
inadequate to allow for firm conclusions. However, it appears that when previous
parotidectomy has been performed, simple excision with a margin of surrounding
tissue would seem appropriate. Parotidectomy should be carried out if not
performed previously. In simple excision after previous parotidectomy, there is a
greater risk to the facial nerve because of difficulty in distinguishing the
facial nerve from surrounding scar tissue. Our preference is to use general
anesthesia so that branches of the nerve are not paralyzed and stimulation of the
nerve aids in safe dissection. The value of RT is still indeterminate.
PMID- 9641274
TI - Advantages of sharp adventitial dissection for microvascular anastomoses.
AB - Adventitia is usually removed from arteries to simplify microvascular
anastomoses. Some surgeons peel the adventitia away bluntly whereas others trim
the adventitia sharply with scissors. We used a rat cremaster flap for intravital
microscopy to evaluate these two techniques. Animals with unmanipulated vessels,
without anastomosis or adventitial removal, served as controls. Fifty-four rats
were studied in three groups of 18 rats. Functional capillary density, red blood
cell velocity, diameter of the flap's feeding artery (A1), microthrombi
formation, and neutrophilic activity were studied for 5 hours following
anastomosis, and 24 and 72 hours later. Histological changes in blunt and sharply
prepared arteries were compared with control vessels. After blunt preparation,
capillary perfusion was reduced to 61% of control values (p < 0.05) and A1
diameter was reduced to 77% of control values (p < 0.05). Capillary perfusion and
A1 diameter were unchanged in sharply prepared arteries. Architectural changes in
the vessel wall were more profound, and neutrophilic activity was increased in
bluntly prepared arteries. In this study, sharp preparation of small arteries was
beneficial compared with blunt preparation.
PMID- 9641275
TI - Treatment of osteonecrosis of the femoral head with free vascularized fibular
transfer.
AB - Thirty-one free vascularized fibular bone grafts were performed for treatment of
osteonecrosis of the femoral head in 26 patients. Twenty-four men and 2 women
ranged in age from 16 to 48 years (mean, 32 years). Twenty-one patients had
unilateral disease. Five patients had bilateral disease and underwent staged
bilateral free vascularized fibular grafts 3 months apart. Associated etiological
factors included alcohol (9 patients), steroid use (7 patients), and trauma (1
patient). The condition was considered idiopathic in the remaining 9 patients.
Radiological staging by Ficat included stage I in 1 hip, stage II in 15 hips,
stage III in 14 hips, and stage IV in 1 hip. A skin island flap was used for
monitoring purposes to check the patency of blood flow to the grafted fibula. One
flap failed by venous occlusion and was left as a nonvascularized bone graft.
Thirty hips were followed. Pain was relieved in 28 hips (93.3%) and aggravated in
2 hips (6.7%). On radiographic evaluation, 26 hips (86.7%) demonstrated excellent
preservation of the femoral head contour. Progressive collapse of the femoral
head (>1-2 mm) occurred in two hips, with 1-mm depression in one hip with stage
III disease and 2-mm collapse in one hip with stage IV disease. Follow-up ranged
from 12 to 40 months (mean, 21 months). In conclusion, even in this relatively
short follow-up period, the free vascularized fibular bone graft is an excellent
treatment modality for preserving the femoral head and relieving symptoms in
patients with osteonecrosis of the femoral head.
PMID- 9641276
TI - Immediate free flap reconstruction for head and neck pediatric malignancies.
AB - We performed six immediate free flap reconstructions after tumor ablation in 5
children under the age of 15 years presenting with head and neck malignancy. One
patient underwent free flap transfer on two separate occasions because of tumor
recurrence. There were no flap losses nor were there any complications related to
microvascular surgery. Although a pediatric head and neck malignant tumor is
rare, surgical resection is the primary therapeutic role for those that are
amenable to complete excision. Pediatric microsurgery provides a safe and
reliable procedure for reconstruction of head and neck defects after extirpation
of the tumor.
PMID- 9641277
TI - Further experience with upper lip flaps for reconstruction of the ala nasi and
alar base defects.
AB - Reconstruction of the ala nasi and the alar base presents problems because of
complex contours, skin color and texture, and limited availability of mobile,
adjacent skin. A large percentage of basal cell carcinomas occur on the nose.
When excised with adequate safety margins, these lesions create a defect too
large for direct repair. This paper describes the use of the upper lip flap for
reconstructing alar base defects and reconstructing the inner lining of the ala
nasi in full-thickness defects of the ala nasi as an alternative to other
procedures proved to be effective on this region. The base of the flap rests on
the base of the columella. It is raised just over the underlying orbicularis oris
muscle. The resulting donor defect is closed primarily. The outer aspect of
defects of the ala nasi are covered with either a full-thickness skin graft, a
forehead flap, or a cheek flap. The upper lip flap was used on 10 patients to
reconstruct full-thickness defects of the ala nasi, for which an alar base needed
to be reconstructed. The results were satisfactory in most patients. An upper lip
flap can be used safely to reconstruct the ala nasi and alar base defects either
alone or in combination with other flaps.
PMID- 9641278
TI - The effect of the suture-induced delay phenomenon on skin flap survival and lipid
peroxidation in rats.
AB - Skin flap ischemia has been associated with the presence of free radicals. In
this study we designed a suture-induced delay model in 30 rats using two
different suture techniques. A total of 13 rats that underwent McFarlane's acute
random-flap model served as controls. We found a statistically significant
difference between the flaps of the experimental and control groups regarding the
viability of flaps. Malondialdehyde levels in tissue samples taken from the
proximal and distal ends of each flap were estimated at 6 and 24 hours
postoperatively. Malondialdehyde levels in the experimental groups were found to
be quite lower than those of the controls. In conclusion, the suture-induced
delay model seems to be effective in improving flap viability. Also, we found
lower malondialdehyde levels in experimental groups compared with controls.
PMID- 9641279
TI - Ischemia/reperfusion injury in flow-through venous flaps.
AB - The effects of ischemia/reperfusion (I/R) injury in flow-through venous flaps
were evaluated in rabbits. The rates of flap survival and the levels of lipid
peroxidation, protein oxidation, and sulfhydryl groups were compared between flow
through venous flaps, conventional flaps after an I/R period (experimental
groups), and flow-through venous flaps without being subjected to I/R injury
(control groups) in 20 animals. On the seventh day after the onset of
reperfusion, 3 of 10 flow-through venous flaps (30%) and 6 of 10 arteriovenous
flaps (60%) survived in the experimental groups. Flow-through venous flaps showed
a decreased survival rate compared with control and conventional flaps (p <
0.05). Tissue lipid peroxide levels were found to be higher in venous flaps
during reperfusion after secondary ischemia (p < 0.05). Tissue protein oxidation
and total sulfhydryl groups levels did not show any difference among groups. This
study suggests that more free radical damage occurs in flow-through venous flaps
during I/R injury.
PMID- 9641280
TI - The influence of ischemia/reperfusion injury on the jejunum.
AB - Ischemia/reperfusion injury (IRI) after free tissue transfer of the small
intestine results in transmural tissue damage. This study examined the effects of
IRI on the jejunum. Wistar rats served either as controls (N=10) or underwent
clamping of the infrarenal aorta for 1 hour followed by 1 hour of reperfusion
(N=10). Both ischemia and reperfusion reduced the protein and deoxyribonucleic
acid content of the jejunal mucosa (p < 0.05). Myeloperoxidase activity in the
jejunal mucosa remained relatively low. The expression of leukocyte function
associated antigen 1 and intercellular adhesion molecule 1 (ICAM-1) on the
surface of mucosal cells was not altered significantly by the ischemic insult,
but was reduced after the period of reperfusion (p < 0.05). This coincided with
an increase in messenger ribonucleic acid (mRNA) for ICAM-1 within isolated
mucosal cells (p < 0.05). The specific activity of glutaminase in isolated
jejunal mucosal cells was diminished after ischemia and reperfusion (p < 0.05),
and this was not associated with an appreciable change in glutaminase mRNA
expression. These results have identified some molecular mechanisms underlying
IRI of the small intestine that are possible candidates for therapeutic
intervention.
PMID- 9641281
TI - A temporal analysis of the effects of pressurized oxygen (HBO) on the pH of
amputated muscle tissue.
AB - The effect of hyperbaric oxygen (HBO) on ischemic muscle tissue pH was evaluated
continuously. The hind limbs of male Sprague-Dawley rats (N=11, both groups) were
amputated and stored in room air (20.1% oxygen [O2], 1.0 ATM, 24 degrees C) or in
HBO (100% O2, 2.9 ATM, 24 degrees C) for 240 minutes. Rat muscle tissue pH was
continuously monitored with a micro-pH electrode following amputation. There was
no significant difference between the average starting tissue pH of control and
treated limbs (p=0.45). At 240 minutes of ischemia the control group tissue pH
decreased 0.80 pH units whereas the treatment group decreased 0.68 pH units (p <
0.05). The tissue pH of control limbs declined 30.7 times faster than treated
limbs during the first 36 minutes of ischemia (p < 0.05). From 36 to 240 minutes
the rates of acidosis were similar and did not differ significantly (p=0.46). In
a separate study, male Sprague-Dawley rats were anesthetized with pentobarbital
and ketamine. Aortic arterial blood gases were obtained at 5 minutes (N=8) and 15
minutes (N=8) postanesthesia. The average serum pH, carbon dioxide, oxygen, and
bicarbonate levels remained within normal limits in both groups and did not
differ significantly (p > 0.05 for all parameters). Anesthesia produced no serum
respiratory or metabolic acidosis and did not contribute to the initial ischemic
tissue pH. These results suggest that HBO delays the progression of metabolic
acidosis in this amputated limb model. This is further supporting evidence for
the tissue-preserving effect of oxygen when delivered in hyperbaric conditions.
However, the clinical application of this technique may be limited due to the
difference in the volume of tissue presented for major limb replantation and the
short window of beneficial effects.
PMID- 9641282
TI - The impact of vasodilators on random-pattern skin flap survival in the rat
following mainstream smoke exposure.
AB - This study demonstrates that acute mainstream cigarette smoke exposure is
deleterious to dorsal random-pattern skin flap survival in the rat. Three
vasodilators were also studied for their ability to mediate flap survival after
smoke exposure. Sprague-Dawley rats (10 per group) were exposed to two cigarettes
per day over a 14-day period. This is an exposure equivalent to that of an
average cigarette smoker. Dorsal McFarlane caudally based random-pattern skin
flaps (4 x 10 cm) were created on day 7 of the smoke exposure. Enteral
phenoxybenzamine (0.56 mg per kilogram per day), enteral nifedipine (10 mg per
kilogram per day), and topical nitroglycerin (1.3 cm or 7.5 mg per day) were
administered after creation of the dorsal skin flaps in two doses daily during
smoke exposure. Fluorescein was used to delineate areas of viability accurately.
A pad digitizer was utilized to calculate designated skin flap areas to +/-1.0
mm2. Experimental animals demonstrated a 23% decrease (p < 0.01) in skin flap
area survival compared with the control animals. The phenoxybenzamine group
demonstrated a 5.5% increase in flap area survival (p=0.068), the nifedipine
group demonstrated a 4.1% increase in flap area survival (p=0.049), and the
nitroglycerin group demonstrated an 8.9% increase in flap area survival
(p=0.049). These data suggest that phenoxybenzamine appears to affect skin flap
survival marginally after smoke exposure. However, nifedipine and nitroglycerin
improve random-pattern skin flap survival significantly after mainstream
cigarette smoke exposure in the rat. These results imply that pharmacological
intervention with vasodilators may ultimately prove clinically useful for random
pattern skin flap salvage in the cigarette-smoking patient.
PMID- 9641283
TI - Salvage treatment for sarcomas of the hand.
AB - We report 6 patients (1 male and 5 females; age range, 13-77 years) with hand
sarcoma. The lesions were located between the digits and the distal end of the
radius. A painless mass was the common manifestation in these patients. An
incisional biopsy was performed on every patient, and histology revealed two low
grade malignant sarcomas and four high-grade malignancies. A surgical salvage
procedure was performed. The 4 patients with high-grade malignancy underwent
adjuvant therapy such as radiotherapy and/or chemotherapy. Four patients are
still alive and exhibit acceptable function in the affected hand. Our surgical
procedure is presented.
PMID- 9641284
TI - The granulometer--a pocket scale for the assessment of wound healing.
AB - In spite of the availability of high-tech devices for wound assessment, plastic
surgeons recognize that the color and confluence of granulation tissue are the
most important indicators of open-wound healing. We developed a simple and
inexpensive pocket-size scale--the Granulometer--to facilitate a finer assessment
and to standardize the documentation of wound healing. This device overcomes
limitations set by conditions such as lighting or recent exposure to other wounds
that could distort the examiner's perception of the wound in question. In this
study we examined the inter- and intraobserver variations in judgment, and the
validity of the Granulometer. Our results demonstrate that skin graft viability
can be predicted accurately by this eight-grade scale. Since graft survival
depends on proper wound healing, we believe that the Granulometer can also be
used for fine assessment of wound treatment. The low inter- and intraobserver
variations indicate that the Granulometer measurements are both reproducible and
accurate.
PMID- 9641285
TI - Endoscopic management of subcutaneous gunshot wound with irrigation technique.
AB - The application of the endoscope to the treatment of gunshot wounds has never
been reported to our knowledge, with the exception of the laparoscope and the
sigmoidscope in abdominal gunshot wounds. We report a patient with a subcutaneous
gunshot wound who was treated endoscopically using the irrigation technique. The
patient was a 25-year-old man who had been shot in the upper arm. The bullet was
found near the thoracic spine via radiograph. At surgery the endoscope was
inserted into the wound and irrigation was started. Excellent views could be
obtained by irrigation, and the endoscope was advanced along the path of the
bullet. The bullet and several fragments were removed with two additional small
incisions. The method described herein seems beneficial in that (1) it is less
invasive than conventional surgical debridement with a long incision, (2) it may
provide information helpful in diagnosing the condition and the location of the
bullet and its path, and (3) saline irrigation may have a cleansing effect.
PMID- 9641286
TI - Endoscopic osteosynthesis for frontal bone fracture.
AB - Endoscopic surgery to repair a frontal bone fracture is described. This operation
is less invasive than the conventional open technique, which is performed under
direct vision through a bicoronal or eyebrow incision. Endoscopic surgery leaves
no conspicuous scars in the forehead and is free from complications such as nerve
or vascular injuries, and appears to be of significant clinical value.
PMID- 9641287
TI - Intercostal thorascopic harvesting of the internal mammary artery for
supercharging a pedicled rectus abdominis flap.
AB - Thorascopic harvesting of the internal mammary artery for supercharging the
rectus abdominis pedicled flap for breast reconstruction is presented. The
procedure was carried on a woman who had previously undergone a mastectomy and
who was obese and a diabetic. The patient underwent a "high" flap delay 2 weeks
earlier. At the time of operative transfer and setting, the flap's vascularity
was found to be compromised. Instead of turbocharging the deep inferior
epigastric pedicle to the irradiated axillary vessels, it was possible to harvest
and utilize the internal mammary artery without rib resection for the
supercharging, thus saving the flap and reconstruction. The technical aspects,
and possible advantages and disadvantages of such a procedure are discussed.
PMID- 9641288
TI - Use of the umbilicus in reconstruction of the vulva and vagina with a rectus
abdominis musculocutaneous flap.
AB - Flap reconstruction of the vulva and vagina following gynecological ablative
procedures has become an integral part of the management of gynecological
oncology patients. The benefits of flap reconstruction, including early primary
healing, improved cosmesis over skin grafting, and prolonged secondary wound
healing, have been well accepted. Additionally, the creation of a neovagina or
neovulva often restores the sexual function and positive body image of the
patient lost to radical procedures. The gracilis musculocutaneous flap has been
used extensively in flap reconstruction but reports of partial flap necrosis and
the need for extensive dissection of both thighs have led to alternative flap
choices. The rectus musculocutaneous flap, with its hardier cutaneous blood
supply, is often too bulky and difficult to inset delicately around the preserved
urethral and vaginal cuff. The umbilicus has the required soft tissue, and its
conically contoured depression allows for delicate insetting of the rectus
abdominis musculocutaneous flap around the urethral cuff. We present 2 patients
who underwent vertical rectus musculocutaneous flaps with umbilical soft tissue
to restore urinary function and to create a cosmetic nonfunctional vagina.
PMID- 9641289
TI - Inverted deepithelialized latissimus dorsi flap for the correction of lumpectomy
defects in the irradiated breast.
AB - Deformities following lumpectomy and radiation can provide reconstructive
challenges for the plastic surgeon. With the increasing incidence of breast
conservation therapy, these problems are likely to become more frequent in the
future. The use of autologous tissue, particularly the latissimus dorsi, provides
an excellent option for correcting these tissue deformities. We propose using an
inverted latissimus with a deepithelialized skin paddle to correct these defects
when there is no shortage of overlying skin. Additionally, this technique
provides a softer texture to the entire radiated breast.
PMID- 9641290
TI - Aneurysms of the superficial temporal artery: literature review and case reports.
AB - Superficial temporal artery (STA) aneurysms are a medical rarity. There are less
than 200 patients reported in the literature. The majority of cases are of
traumatic etiology and occur in young men. The senior authors reported a case of
STA aneurysm in 1978. We now review the literature and report on three additional
patients with STA aneurysm and a fourth patient with a temporal lipoma that was
diagnosed initially as an aneurysm. This is the first report of a preoperative
diagnosis of STA aneurysm that subsequently proved incorrect.
PMID- 9641291
TI - Endometrioma of the abdominal wall following combined abdominoplasty and
hysterectomy: case report and review of the literature.
AB - An unusual case is reported of abdominal wall endometrioma presenting in a lower
abdominal scar following a combined hysterectomy and abdominoplasty performed 5
years earlier. Current diagnostic methods and recommended surgical management are
outlined.
PMID- 9641292
TI - Muir-Torre syndrome.
AB - Muir-Torre syndrome is a rare autosomal dominant disorder characterized by
unusual sebaceous neoplasms and visceral malignancy. Excluding sebaceous
hyperplasia and sebaceous nevus of Jadassohn, sebaceous neoplasms occur so rarely
that the presence of a sebaceous neoplasm mandates consideration of Muir-Torre
syndrome. Sebaceous neoplasms precede or are synchronous with visceral
malignancies in up to 40% or more of patients with Muir-Torre syndrome, and the
presence of such a lesion warrants an evaluation for visceral malignancy.
PMID- 9641293
TI - Gynecomastia of the male nipple.
AB - Diseases of the male nipple can be responsible for severe problems for the
patient. The location of gynecomastia can be restricted to the nipple. Carcinoma
should also be considered. The therapy of choice is operative treatment. A subtle
microsurgical procedure is helpful to achieve a good functional and cosmetic
result.
PMID- 9641294
TI - Residency training: how long and by what method?
PMID- 9641295
TI - Management guidelines for uninvestigated and functional dyspepsia in the Asia
Pacific region: First Asian Pacific Working Party on Functional Dyspepsia.
AB - Dyspepsia is most optimally defined as pain or discomfort centred in the upper
abdomen. The symptom complex may be caused by peptic ulcer disease, gastro
oesophageal reflux, or gastric cancer but is most often due to functional (or non
ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the
underlying cause of dyspepsia, it is expensive. A more pragmatic approach is
needed in the Asia Pacific region where health services are limited. A detailed
treatment algorithm is given for managing patients presenting with new-onset
dyspepsia and documented functional dyspepsia after endoscopy, and evidence to
support this approach is reviewed. Prompt endoscopy is recommended for patients
with alarm features. In patients without alarm features, treatment for 2-4 weeks
with an empirical anti-secretory or prokinetic agent, followed by investigation
using non-invasive Helicobacter pylori testing and treatment for patients who do
not respond or relapse, is recommended. Trials of management strategies are now
needed to establish the efficacy and cost-effectiveness of the approaches
recommended.
PMID- 9641296
TI - Infection, sepsis and systemic inflammatory response syndrome in obstructive
jaundice.
PMID- 9641297
TI - Rising incidence of oesophageal adenocarcinoma in men in Australia.
AB - Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to
be increasing in incidence in many countries, while the incidence of squamous
cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are
decreasing in incidence. Age-standardized incidence rates for the years 1982-1993
for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non
cardia cancers were calculated based on state cancer registry incidence data.
Time trends in the age-standardized rates were assessed using linear regression.
A consistent increasing trend in the incidence of oesophageal adenocarcinoma in
men was seen in all states of Australia and was statistically significant in all
states except South Australia. There were no consistent nationwide trends in the
incidence of oesophageal adenocarcinoma in women, although a trend towards an
increase in the incidence of this cancer reached statistical significance (P <
0.05) in three states (New South Wales, Victoria, Queensland). There were no
important trends in the incidence of oesophageal non-adenocarcinoma in either men
or women. There were no consistent nationwide changes in the incidence of gastric
cardia cancer in either men or women, although this cancer was significantly
increasing in Tasmania in both men and women. The incidence of cancer of the
stomach not arising at the gastric cardia was significantly decreasing in men in
all states and was also decreasing in women in all states, although in women this
decrease was statistically significant only in New South Wales, Victoria and
Western Australia. There has been a dramatic increase in the incidence of
oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in
men is now approximately equal with that of non-adenocarcinoma of the oesophagus.
The incidence of non-cardia stomach cancer continues to fall.
PMID- 9641298
TI - Oral human spasmolytic polypeptide protects against aspirin-induced gastric
injury in rats.
AB - Spasmolytic polypeptide (SP) is a member of the trefoil peptide family; gut
peptides that participate in the protection and repair of the gastric mucosa.
Previous studies have failed to agree on the mode of action of human SP (hSP). We
investigated the effect of orally administered human SP on the protection and
repair of rat gastric mucosa in an established in vivo model of damage induced by
the non-steroidal anti-inflammatory drug aspirin (ASA). The integrity of the
gastric mucosa was quantified in four ways: the temporal change in transmucosal
potential difference (PD), area of macroscopic damage by planimetry, relative
area of microscopic damage by histological morphometry, and the number of deep
erosions per centimetre of mucosa sectioned. Human SP (200 micromol/L)
administered orally before, or in combination with ASA significantly reduced the
fall in PD, the area of microscopic damage, and the number of deep erosions (P <
0.05). The area of macroscopic damage was significantly reduced only in rats
where hSP (200 micromol/L) was given in conjunction with ASA (P < 0.05). Human
spasmolytic polypeptide (70 or 200 micromol/L) administered after ASA failed to
hasten the re-establishment of PD or stimulate the repair of the gastric mucosa
in the 90 min following injury (P > 0.05, compared with ASA alone). We conclude
that hSP prevents gastric mucosal damage by its topical actions, probably by a
rapid interaction with luminal mucins or epithelial cells, but fails to stimulate
early restitution in the injured gastric mucosa.
PMID- 9641299
TI - Percutaneous endoscopic gastrostomy feeding in AIDS.
AB - Reduced energy intake is the most important reason for weight loss in advanced
human immunodeficiency virus (HIV) infection. From January 1989 to August 1995
enteral feeding via a percutaneous endoscopic gastrostomy tube (PEG) was offered
to all human immunodeficiency virus(HIV)/AIDS patients attending Fairfield
Hospital, Melbourne who were unable to maintain 85% ideal body weight. A total of
71 patients received enteral feeding (1000-2000 kcal/day) for a median period of
161 days (range 4-644 days). Fifty-one (72%) patients gained 5.8 +/- 4.4kg (range
0.4-19.2 kg). Nine gained 10 kg or more. The median time to maximum weight was 74
days after PEG insertion. Those who gained weight had a longer median survival,
but this difference was not statistically significant (210 vs 109 days, P =
0.07). The only predictor of weight gain was a CD4 count greater than 100/microL.
Patients who gained weight reported improved quality of life and increased
independence. However, early complications, especially wound infection, were
common. Although these data have been gathered retrospectively, our experience
suggests that enteral feeding can maintain or improve nutritional status and may
improve quality of life in advanced HIV infection.
PMID- 9641300
TI - Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer
healing.
AB - Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers
was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12
normal subjects were investigated. Biopsy samples were obtained during endoscopic
examination and subjected to DNA analysis by flow cytometry. Thirty patients with
duodenal ulcers were healed within 3 months with H2 blockers (tractable or
responsive ulcers), whereas 10 patients did not respond to treatment (intractable
ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell
proliferation, was constant in the adjacent duodenal mucosa 2 cm from ulcer
margin and antral mucosa during duodenal ulcer healing. The index at the margin
of tractable ulcers was elevated during the active stage (12.9 +/- 1.3), peaked
during the healing stage (15.4 +/- 2.8) and returned to the same level at the
scarring stage (10.9 +/- 2.0) as normal controls (10.3 +/- 1.7). However, the
index was not elevated in intractable ulcers (10.3 +/- 1.7 in the healing stage)
and was smaller than in tractable ulcers. These data indicate that augmented
mucosal cell proliferation at the ulcer margin plays an important role in
duodenal ulcer healing and intractable ulcers are characterized by an abnormal
failure to accelerate DNA synthesis to achieve ulcer repair.
PMID- 9641301
TI - Case report: Spontaneous isolated mesenteric fibromatosis presenting as
megaduodenum.
AB - A case of spontaneous isolated mesenteric fibromatosis presenting as megaduodenum
is reported. The lesion was small, only 2 cm in its greatest diameter. However,
because of its location near the ligament of Treitz and because of its
characteristic infiltrative growth pattern, the tumour involved the distal
duodenum and resulted in acute angulation and obstruction early in its course. We
successfully resected the mass and the patient is in fair physical condition 6
months after operation.
PMID- 9641302
TI - Case report: Haemangioma of the small intestine complicated by protein-losing
gastroenteropathy.
AB - We report a case of haemangioma of the small intestine complicated by protein
losing gastroenteropathy. A 32-year-old female had suffered from hypoproteinaemia
for 6 years, but the cause of this condition had not been determined. On
diagnosis and therapy for hypoproteinaemia, intra-operative endoscopy and
histological examination were performed and she was subsequently diagnosed with
capillary haemangioma of the small intestine. Angiography was not useful for the
detection of capillary haemangioma of the small intestine in this case. Although
intestinal haemangioma is an important cause of gastrointestinal bleeding,
protein loss is an extremely rare complication and this case is the first to be
reported in Japan.
PMID- 9641303
TI - Greatly increased mucosal nitric oxide in ulcerative colitis determined in situ
by a novel nitric oxide-selective microelectrode.
AB - Although current nitric oxide (NO) electrodes are simple, selective and
sensitive, they are fragile and hard to use in clinical studies of patients. By
preparing an improved NO electroneedle that overcomes these defects, we directly
measured mucosal NO concentrations in 11 patients (six male, five female; mean
26.0 years old) with ulcerative colitis (UC) and five normal volunteers (three
male, two female; mean 28.3 years old) in situ. An electroneedle was inserted
into colonic mucosa through a biopsy channel during colonoscopy. The information
concerning the concentration of NO generated and the appearances of the colonic
mucosa at the same site were obtained simultaneously. In the ulcerative colitis
patients, NO concentrations were significantly increased at all 24 mucosal sites
tested. These included sites where: there was an absence of visible inflammation
(five sites); the mucosa was mildly inflamed (eight sites); the mucosa was
moderately inflamed (five sites); or severely inflamed (six sites). The NO
concentrations in ulcerative colitis patients were 12-72 times higher than the NO
levels in normal controls (10 sites). At the same 10 sites in four ulcerative
colitis patients, the high NO concentrations were decreased by 53% after
glucocorticoid treatment. These data are consistent with those of previous
studies utilizing different NO electrodes. Excess mucosal NO is generated from
inducible NO synthase in the inflamed mucosa itself and the invading inflammatory
cells. Our results suggested that mucosal NO could be a marker for the extent of
inflammation and its various actions correlated with the pathogenesis, natural
history and prognosis of UC. Using the NO microelectrode system reported here,
the concentration of NO generated can be monitored in real-time while observing
the mucosal condition at the same site during endoscopy. This novel NO electrode
may contribute to understanding the role of NO in colonic mucosal inflammation.
PMID- 9641304
TI - A study of laboratory based faecal occult blood testing in Melbourne, Australia.
The Faecal Occult Blood Testing Study Group.
AB - Faecal occult blood tests (FOBT) are widely used in clinical practice and are
under increasing scrutiny as a tool for colorectal cancer screening. However,
there is little information regarding the quality of testing performed in
pathology laboratories. Therefore, we asked 13 pathology laboratories in
Melbourne, Australia, to test coded contrived faecal samples prepared from a
composite stool specimen which had been spiked to various concentrations of
haemoglobin. The samples were provided to the laboratories in two forms: (i)
on/in the sample collection device appropriate for the faecal occult blood test
they normally used; and (ii) as a moist faecal sample. Some variation in
threshold analytical sensitivity between laboratories for the same FOBT was
observed for Hemoccult SENSA, ColoRectal, Hematest, MonoHaem and Hemolex
suggesting that, at least for those tests, technician training could be improved.
Two tests, Hematest and an in-house FOBT did not perform as well as the other
FOBT. When samples were sent in moist form, Hemoccult SENSA (P = 0.0002),
ColoRectal (P = 0.02) and MonoHaem (P = 0.04) had significantly lower overall
positivity rates; for Hemolex the decrease was not significant (P = 0.3). The
lower positivity rate with moist samples is important, given that 11 of the 13
laboratories in the study stated that they receive at least some samples in moist
form. Thus, technician training and laboratory procedure need to be reviewed to
maximize the benefits of faecal occult blood testing in clinical practice,
especially with its expanding role in colorectal cancer screening.
PMID- 9641305
TI - Case report: an inherited APC mutation in the first reported Australian case of
Turcot's syndrome.
AB - The objective of this study was to determine the inherited gene mutation
responsible for the first reported Australian case of Turcot's syndrome. DNA was
extracted from the archival tissue blocks obtained at the time of the patient's
original surgery and from fresh blood samples obtained from selected family
members. These were analysed for mutations of the familial adenomatous polyposis
gene (APC). Analysis of DNA from the archival blocks and from each of the
affected family members revealed an inherited 5 base pair deletion at codon 1061
of APC. In this case, the central nervous system tumour represents an
extracolonic manifestation of familial adenomatous polyposis. The underlying
inherited mutation of APC has been identified. In some cases of Turcot's
syndrome, other genes appear to be involved. Recent literature examining the
molecular basis of Turcot's syndrome is reviewed.
PMID- 9641306
TI - Effect of obstructive jaundice on neutrophil chemotactic activity: an in vivo
assessment in zymosan-induced peritonitis model in rats.
AB - The effect of obstructive jaundice on local neutrophil accumulation in response
to inflammatory stimulus was investigated in rats. Obstructive jaundice was
produced by bile duct ligation for 7 days. Zymosan (200 mg) was injected
intraperitoneally and 4h later myeloperoxidase activity in the peritoneal fluid
was measured to quantify neutrophil recruitment. Zymosan-induced neutrophil
recruitment was significantly greater (more than two-fold) in bile duct-ligated
rats than in sham-ligated or normal animals. Depletion of peritoneal cells
significantly suppressed neutrophil recruitment after zymosan injection in all
three groups, with no significant differences between the groups. In normal rats,
replacement of their peritoneal cells by those from bile duct-ligated rats did
not enhance zymosan-induced neutrophil recruitment. In contrast, bile duct
ligated rats treated with peritoneal cell replacement from normals showed
significantly increased neutrophil recruitment after zymosan injection. In vitro
neutrophil chemotaxis in response to formyl-Met-Leu-Phe was significantly
enhanced in bile duct-ligated rats, compared with that in sham-ligated animals.
The results suggest that local neutrophil recruitment in response to inflammation
may be enhanced in obstructive jaundice and that increased neutrophil chemotactic
activity, not macrophage activity, may play a prime role in the mechanism.
PMID- 9641307
TI - Predictive factors in eradicating hepatitis C virus using a relatively small dose
of interferon.
AB - Interferon (IFN) can reduce hepatitis C virus load and even eliminate the virus
in 30-40% of patients. Several predictive factors for eradication of the virus
have been reported and a higher dose of IFN tends to result in elimination of the
virus. However, a small dose of IFN sometimes is as effective as a large dose in
eradicating the virus. The predictive factors for such a response are not well
established. We retrospectively analysed 50 patients with chronic hepatitis C who
were treated with relatively small amounts of IFN (equal or less than 252 million
units). Eleven patients were responders (elimination of hepatitis C virus (HCV)
and normalization of alanine amino transferase (ALT) for at least 6 months), but
the remaining 39 were non-responders. Multivariate analysis showed that the
pretreatment viral load and total dose of IFN per kilogram of bodyweight were
significant predictive factors of response to therapy. We also assessed the amino
acid substitutions in the IFN sensitivity determining region (ISDR), NS5A codon
2209-2248, of HCV in serum samples obtained from 31 patients with HCV genotype
1b. The presence of more than one amino acid substitution in the ISDR tended to
correlate with HCV genotype 1b elimination. As IFN is expensive and has a number
of serious side effects, our study suggests that the optimal dose of IFN may vary
from one patient to another and that more stringent criteria should be used to
select the optimal dose for therapy.
PMID- 9641308
TI - How much does alcohol contribute to the variability of hepatic fibrosis in
chronic hepatitis C?
AB - In order to determine the contribution of alcohol intake to the severity of
hepatic fibrosis in patients with chronic hepatitis C, we studied associations
between various levels of alcohol intake, other demographic variables and
semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical,
demographic and disease-related data were entered into a relational database.
Liver histology was scored according to Scheuer. The average daily alcohol intake
for the year preceding liver biopsy (recent exposure) and for earlier periods
(past exposure) was categorized into five levels of intake. One-third of patients
gave a history of alcohol intake that had exceeded 40 g/day for at least 5 years.
By univariate analysis, age, but not recent or past alcohol intake or other
baseline variables, was associated with portal score (r = 0.14, P = 0.004),
fibrosis score (r = 0.46, P < 0.001), total Scheuer score (r = 0.35, P < 0.001).
However, by multivariate analysis, age (P < 0.001), past (but not present)
alcohol intake (P < 0.001) and birth in Egypt (P = 0.006) were independently
associated with fibrosis score. Age, past alcohol and birth place in Egypt
contributed 27% to total variance of the hepatic fibrosis score, while age alone
accounted for 23%. Age also independently predicted portal activity (P = 0.02)
and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with
total Scheuer score (P = 0.002) but not with other histological indices. A
separate multivariate analysis was performed on a more homogeneous subgroup of
196 patients who acquired hepatitis C by injection drug use. In this subgroup,
age (P < 0.05) and past alcohol (P < 0.05) were independently associated with
fibrosis score. In both the overall and subgroup analyses, there was a threshold
level of past alcohol intake (>80 g/day) beyond which the risk of fibrosis
increased significantly. It is concluded that toxic levels of alcohol exposure
for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence
of alcohol appears to be minor compared with age and other variables and is
exerted only at toxic levels of intake.
PMID- 9641309
TI - Effects of colchicine and phenothiazine on biliary excretion of organic anions in
rats.
AB - Vesicular transport inhibitors have been reported to inhibit biliary excretion of
some organic anions, suggesting that vesicular transport has a role in
intracellular transport of these compounds. However, these inhibitors are
substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in
canalicular transport of organic anions in addition to the canalicular
multispecific organic anion transporter, we studied the effect of colchicine, a
vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein
expression on biliary excretion of various organic anions in rats. Colchicine
treatment slightly but significantly inhibited biliary excretion of indocyanine
green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary
excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine
treatment did not affect biliary excretion of indocyanine green and pravastatin,
but it increased biliary sulphobromophthalein-glutathione excretion. In
conclusion, the present findings suggest that P-glycoprotein plays an additive
role on biliary excretion of some organic anions in addition to the canalicular
multispecific organic anion transporter.
PMID- 9641310
TI - Hepatobiliary images. Pancreatic pseudocysts in the liver.
PMID- 9641311
TI - Images in gastroenterology. Gastric antral vascular ectasia (watermelon stomach).
PMID- 9641312
TI - The liver in traditional Chinese medicine.
AB - Medical thinkers in China visualized the liver in microcosmal and macrocosmal
terms. An anatomical tradition did not exist, hence the liver was described
grossly in broad outline. It was recognized as being functionally important in
the movement of qi (vital energy) and storage of xue ('blood'). The liver
corresponded to various phenomena in both the natural and social orders,
according to the scheme of yin yang and five phases. These interrelationships
provided the basis for the diagnosis and treatment of liver dysfunctions. The
disorders fell into three general groups: (i) hepatic qi stasis; (ii) hepatic
yang excess with yin deficiency; and (iii) hepatic yin insufficiency. The signs
and symptoms represented the logical outcomes of the disturbed physiology.
Acupuncture, moxibustion and herbal drugs were used to redress the imbalance of
hepatic qi and yin-yang. The impact of Western medicine led traditional authors
to recognize the hepatobiliary role in bile secretion and in jaundice. The
exchange between the Western and Chinese medical traditions revealed that active
agents were included in the Chinese formulary, such as glycyrrhizin, which has
recently been shown to be beneficial in chronic viral hepatitis.
PMID- 9641313
TI - Current risks of viral hepatitis from blood transfusions.
AB - The incidence of transfusion-associated hepatitis in the United States has fallen
dramatically since the late 1960s. Where once the risks were so great that as
many as one in three transfused patients contracted hepatitis, now they are
infinitesimal. Many factors share responsibility for this accomplishment;
however, two stand above the rest: (i) improved donor selection and screening
criteria, especially elimination of paid blood donations; and (ii) major advances
in testing for viral hepatitis carriers. Currently, four tests are used for the
prevention of transfusion-associated hepatitis: (i) hepatitis B surface antigen;
(ii) hepatitis C virus antibody; (iii) hepatitis B core antibody; and (iv)
alanine aminotransferase. The first two tests are largely responsible for the
current low risks of transfusion-associated hepatitis due to hepatitis B virus
and hepatitis C virus of 1 in 63,000 and 1 in 125,000, per unit, respectively. To
further reduce the risks of transfusion-associated hepatitis will require the
enhanced sensitivity provided by nucleic acid amplification techniques (e.g.
polymerase chain reaction). Currently, however, no such tests are licensed and
practical, automated, or inexpensive enough for individual blood donor screening.
We have made such great strides in the prevention of transfusion-transmitted
hepatitis that background rates of viral hepatitis now greatly exceed the risk of
transmission via transfusion. For this reason, while it may still be reasonable
to consider a transfusion as a possible cause for hepatitis, it is imperative
that many other possibilities (e.g., iatrogenic and other risk factors) be ruled
out.
PMID- 9641314
TI - Fluorescence imaging of Na+ influx via P2X receptors in cochlear hair cells.
AB - The adenosine 5'-triphosphate (ATP)-activated membrane conductance, mediated by
P2X receptors, was examined in isolated guinea-pig cochlear inner and outer hair
cells. Photo-activated release of caged-ATP elicted a 30-ms latency inwardly
rectifying non-selective cation conductance, blocked by the P2X receptor
antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10-100
microM), consistent with the direct activation of ATP-gated ion channels. A K(Ca)
conductance in the inner hair cells (IHC), activated by the entry of Ca2+ through
the ATP-gated ion channels, was blocked by including 10 mM 1,2-his(2
aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the internal solution.
Real-time confocal slit-scanning fluorescence imaging of Na+ influx through the
ATP-gated ion channels was performed using the dye Sodium Green with simultaneous
whole-cell recording of membrane currents. The Na+ entry was localized to the
endolymphatic surface, with the increase in [Na+]i detected within approximately
200 ms of the onset of the inward current response. Within 600 ms Na+ had
diffused throughout the cell cytoplasm with the exception of the subnuclear
region of the outer hair cells. Correlation of voltage-clamp measurements of Na+
entry with regional increases in Na+-induced fluorescence demonstrated ATP
induced increases in intracellular Na+ in excess of 45 mM within 4 s. These data
provide direct evidence for the Na+ permeability of the ATP-gated ion channels as
well as independent evidence for the localization of P2X receptors at the
endolymphatic surface of the sensory hair cells. The localization of the ATP
gated ion channels to the apical surface of the hair cells supports an ATP
mediated modulation of 'silent' K+ current across the cochlear partition which
could regulate hearing sensitivity by controlling the transcellular driving force
for both mechanoelectrical and electromechanical transduction in hair cells.
PMID- 9641315
TI - Estimating cochlear filter response properties from distortion product
otoacoustic emission (DPOAE) phase delay measurements in normal hearing human
adults.
AB - This study examined cochlear filter response properties derived from f1- and f2
sweep phase delay difference measures in 60 normal hearing human adults. Seven
different f2 frequencies ranging from 1.1 to 9.2 kHz were presented (f2/f1 ratios
of 1.1-1.3). F2 intensity level was varied in 5 dB steps from 30 to 50 dB SPL
(the level of f1 was 15 dB above the level of f2). DPOAE delay estimates in a f2
sweep paradigm are longer than in a f1-sweep paradigm at the same frequency and
intensity. This indicates that the f2-sweep DPOAE phase delay is composed of a
greater proportion of the filter response time at the site of DPOAE generation
than the f1-sweep delay. This proportion was isolated by subtracting f1-sweep
DPOAE delays from f2-sweep delays at similar f2 frequencies and intensities.
Under the assumption of linearity and minimum phase the impulse response of the
filter at each f2 stimulus level was calculated from the mean phase delay
difference. Frequency response properties were calculated by Fourier
transformation of the impulse response at each f2 frequency and intensity. High
frequency low intensity impulse responses had longer response times and narrower
frequency bandwidths than low frequency high intensity responses. The Q10dB
values of DPOAE derived tuning curves ranged from 2.4 (1.5 kHz) to 7.3 (8.5 kHz).
PMID- 9641316
TI - Genetics of age-related hearing loss in mice. IV. Cochlear pathology and hearing
loss in 25 BXD recombinant inbred mouse strains.
AB - The effects of three putative genes which contribute to age-related hearing loss
(AHL genes) were evaluated using auditory brainstem response (ABR) thresholds and
post-mortem cochlear histopathology in 25 recombinant BXD inbred mouse strains,
originally derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. All BXD
strains showed substantial elevation of ABR thresholds and loss of spiral
ganglion cells (SGCs) during the first year of life. The findings are consistent
with our genetic model in which D2 and B6 inbred strains both possess the Ahl
(age-related hearing loss) gene, whereas D2 possesses two additional chromosomal
loci with AHL genes (Ahl2 and Ahl3). The between-strain distribution in the
severity of SGC loss and ABR threshold elevations suggests that the severity of
hearing loss is determined in large part by the number of AH L genes an animal
possesses and by additional genetic background effects. The present findings also
demonstrate that, because BXD strains vary substantially in the rate and severity
of progressive hearing loss (but are genetically closely related), they can
provide powerful animal models for developmental studies of AHL.
PMID- 9641317
TI - Passive sound-localization ability of the big brown bat (Eptesicus fuscus).
AB - The passive sound-localization ability (i.e. minimum audible angle) of the big
brown bat, Eptesicus fuscus, was determined using a conditioned avoidance
procedure in which the animals were trained to discriminate left sounds from
right sounds. The mean threshold of three bats for a 100-ms broadband noise burst
was 14 degrees, a value that is about average for mammals. A similar threshold of
15 degrees was obtained for one animal when it was retested with one of its own
recorded echolocation calls as the stimulus. The two bats tested on pure-tone
localization were able to localize high-frequency, but not low-frequency tones,
even when a low-frequency tone was amplitude modulated, a result indicating that
these bats are not able to use binaural time-difference cues for localization.
Finally, given the width of the bat's field of best vision, as determined by a
count of its ganglion-cell density, its sound-localization acuity is consistent
with the hypothesis that the role of passive sound localization is to direct the
eyes to the source of a sound.
PMID- 9641318
TI - Perceptual consequences of the interactions between spontaneous otoacoustic
emissions and external tones. I. Monaural diplacusis and aftertones.
AB - Research into monaural diplacusis has led to the concept of idiotones (tone-like
stimuli of cochlea origin). Spontaneous otoacoustic emissions (SOAEs) are tone
like stimuli generated by the cochlea and detected in the ear canal. In
diplacusis, the existence of idiotones is inferred from disturbances of the
perception of single tones. Spontaneous otoacoustic emissions are measured by
placing a small microphone at the entrance to the ear canal. Many of the puzzling
properties of the hypothesized idiotones are consistent with measurements of the
interaction of SOAEs with external tones. The interactions of the SOAEs with
external tones were analyzed acoustically. The perceptual properties evoked by
250 ms pulses (presented twice a second) of the acoustic stimuli used in the OAE
experiments were systematically investigated. At some stimulus levels, all
subjects reported the perception of a second tone alternating with the external
tone. The relative pitch of this percept was consistent with the frequency of the
SOAE. The frequency dependence of the signal levels needed for the percept had
many aspects in common with the suppression tuning curves of the SOAEs. At lower
levels of the external tone the subjects sometimes reported a perception of two
simultaneous tones. This would be consistent with the subject detecting SOAEs
when they are frequency shifted, but not suppressed. The consumption of aspirin
by one subject reduced the SOAE into the noise floor and eliminated the monaural
diplacusis.
PMID- 9641319
TI - Changes in cochlear blood flow due to intra-arterial infusions of angiotensin II
(3-8) (angiotensin IV) in guinea pigs.
AB - The effects of a newly discovered form of angiotensin, angiotensin IV (ANGIV), on
cochlear blood flow (CBF) have been investigated utilizing the laser Doppler
flowmetry (LDF) technique. Two specific questions were addressed: What are the
effects of anterior inferior cerebellar artery infusions (AICA) of ANGIV on CBF
and do angiotensin fragments other than ANGIV influence CBF in mature male and
female guinea pigs. Infusions of ANGIV, and C-terminal shortened fragments were
accomplished via micropipette into the AICA and changes in CBF were observed
using LDF. The results demonstrated that 10 and 100 pmol/min doses of ANGIV
increased CBF 22% and 75% (n = 6; P < 0.01) from baseline, respectively, with
little change in mean arterial blood pressure (MAP). Pretreatment with the ANGIV
antagonist divalanal-ANGIV (1 nmole/min) blocked increases in CBF due to
infusions of 100 pmol/min of ANGIV. The infusion of the C-terminal shortened
fragment ANGIV(1-5) and saline had no significant effect on either CBF or MAP.
These results provide the evidence for a new subtype of the angiotensin receptor
and indicate the likely role of circulating hormones in blood flow regulation in
the inner ear.
PMID- 9641320
TI - The dorsal cochlear nucleus contributes to a high intensity component of the
acoustic startle reflex in rats.
AB - The dorsal cochlear nucleus (DCN) has been shown to project to a region of the
nucleus reticularis pontis caudalis (PnC) critical for the evocation of startle
in rats, suggesting a possible modulatory influence of the DCN on startle. This
study examined the involvement of the DCN in the acoustic startle reflex and
various other forms of behavioral plasticity seen with this response. Animals
received bilateral electrolytic lesions of the DCN and were tested for acoustic
startle responses, background noise facilitation, short-term habituation,
prepulse inhibition and facilitation, and fear conditioning. Compared to sham
lesioned rats, DCN lesioned rats showed a significant reduction in startle
amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL)
and normal responses on all other measures. Hence, the DCN appears to contribute
to a high intensity component of the acoustic startle response in rats.
PMID- 9641321
TI - Intercellular junctional maturation in the stria vascularis: possible association
with onset and rise of endocochlear potential.
AB - The postnatal maturation of intercellular junctions of marginal and basal cells
of the stria vascularis was examined in the gerbil using thin sections and freeze
fracture techniques. Immunohistochemical methods were used to determine the
presence of Na,K-ATPase postnatally. The onset and growth of endocochlear
potential (EP) was also measured. In marginal cells, the apical surface and
junctional region around the apical pole of the cell was found to have adult-like
characteristics by the time of onset of EP, whilst the increase in staining for
Na.K-ATPase temporally coincided with an increasing density of intra-membrane
protein particles on the infoldings of marginal cell lateral membranes.
Maturation of the junctional specialisations of the basal cells was found to
correspond temporally with the period of onset and rise of EP. Tight junctions
between basal cells first appeared as small, broken strands composed of widely
spaced particles at 6 days after birth (DAB). These junctional strands increased
in number and in particle density until adult-like at 16 DAB when they covered
large areas of the basal cell lateral membrane. Gap junctions on the apical
membrane of basal cells first appeared as small patches of loosely packed
junctional elements at 6 DAB. Between 8 and 16 DAB the area of membrane occupied
by the gap junctions increased, reaching a mature conformation by 18 DAB. The
results suggest that EP maturation is dependent upon the development of sealing
between the basal cells by tight junctions and also the establishment and
development of gap junctions in the apical plasma membrane of basal cells,
associated with intermediate cells.
PMID- 9641322
TI - Ultrastructural localization of ChAT-like immunoreactivity in the human
vestibular periphery.
AB - Acetylcholine (ACh) has long been considered a neurotransmitter candidate in the
efferent vestibular system of mammals. Recently, choline acetyltransferase
(ChAT), the synthesizing enzyme for ACh, was immunocytochemically localized in
all five end-organs of the rat vestibule (Kong et al. (1994) Hear. Res. 75, 192
200). However, there is little information in the literature concerning the
cholinergic innervation in the vestibular periphery of man. In the present study
the ultrastructural localization of the ChAT-like immunoreactivity in the human
vestibular periphery was investigated in order to reveal the cholinergic
innervation in the human vestibular end-organs. A modified method of pre
embedding immunoelectron microscopy was applied. It was found that the ChAT-like
immunoreactivity was located in the bouton-type vesiculated nerve terminals in
the vestibular neurosensory epithelia of man. These ChAT-like immunostained nerve
terminals make synaptic contacts either with afferent chalices surrounding type I
vestibular sensory hair cells, or with type II vestibular sensory hair cells.
These results show that the ChAT-like immunoreactivity in the human vestibular
periphery is confined to the efferent vestibular system. The ChAT-containing
efferents innervate both type I hair cells and type II hair cells, making
postsynaptic and presynaptic contacts, respectively. This study presents evidence
that ACh is a neurotransmitter candidate in the efferent vestibular system of
man.
PMID- 9641323
TI - Ultrastructural localization of GABA-like immunoreactivity in the human utricular
macula.
AB - In the vertebrate vestibular periphery, gamma-aminobutyric acid (GABA) has long
been presumed to be a neurotransmitter candidate. However, experimental reports
about the localization and function of GABA in the vestibular systems of
vertebrates are contradictory. In addition, there is no information in the
literature concerning the localization of GABA in the human vestibular periphery.
The present study investigates the ultrastructural localization of GABA-like
immunoreactivity in the human utricular macula. A modified pre-embedding
immunostaining electron microscopy technique was applied using two different
commercially available polyclonal antibodies to GABA. GABA-like immunoreactivity
is confined to the vesiculated nerve fibers and terminals of the human vestibular
neurosensory epithelia. The GABA-containing nerve terminals make asymmetrical axo
dendritic synapses with the afferent chalices surrounding the type I sensory hair
cells. Type I and type II hair cells as well as afferent chalices are devoid of
GABA-like immunoreactive staining. The present study demonstrates that GABA
exists in the human vestibular periphery, and that GABA is a neurotransmitter
candidate of the human efferent vestibular system.
PMID- 9641324
TI - Alpha1A-adrenergic receptors mediate vasoconstriction of the isolated spiral
modiolar artery in vitro.
AB - Several lines of evidence suggest that cochlear blood flow is under the control
of the sympathetic nervous system and that this control is mediated via alpha
adrenergic receptors. The goal of the present study was to determine whether
alpha-adrenergic receptors mediate vasoconstriction of the spiral modiolar artery
and, if so, to determine which subtype dominates this response. Vascular diameter
was measured with video microscopy in the isolated superfused spiral modiolar
artery in vitro. The diameter of the spiral modiolar artery under control
conditions was 61 +/- 2 microm (n = 60). Spontaneous vasomotion was observed in
most specimens. Addition of norepinephrine to the superfusate caused a phasic
vasoconstriction and an increase in the amplitude of vasomotion. These effects
were limited to the vicinity of arteriolar branch points of the spiral modiolar
artery. Norepinephrine-induced vasoconstriction occurred with EC50 of (1.9 +/-
0.4) x 10(-5) M (n = 44) and the vascular diameter was maximally reduced by a
factor of 0.87 +/- 0.01 (n = 29). Neither the phasic nature nor the EC50 of the
norepinephrine-induced vasoconstrictions was altered in the presence of the beta2
adrenergic receptor antagonist 10(-5) M ICI118551 or the nitric oxide synthase
inhibitor 10(-4) M NOARG. In contrast, the alpha2-adrenergic receptor antagonist
10(-7) M yohimbine and the alpha1-adrenergic receptor antagonist 10(-9) and 10(
8) M prazosin caused a significant shift in the dose-response curve. The affinity
constants (K(DB)) for yohimbine and prazosin were (5+/-2) x 10(-8) M (n=4) and
(2.0+/-0.7) x 10(-10) M (n=18), respectively. The alpha1A-adrenergic receptor
antagonist 10(-8) M 5-methyl urapidil and the alpha1D-adrenergic receptors
antagonist 5 x 10(-6) M BMY7378 caused a significant shift in the dose-response
curve. The K(DB) values for 5-methyl urapidil and for BMY7378 were (2.7 +/- 0.7)
x 10(-10) M (n = 8) and (4.4 +/- 2.7) x 10(-7) M (n = 8), respectively. Further,
total RNA was isolated from microdissected spiral modiolar arteries and the
presence of transcripts for alpha1-adrenergic receptor subtypes was determined by
reverse transcription polymerase chain reaction (RT-PCR). Primers specific for
gerbil alpha1-adrenergic receptor subtypes were developed using RNA from rat and
gerbil brain. Analysis of RNA extracted from the spiral modiolar artery revealed
RT-PCR products of the appropriate size for the alpha1A-adrenergic receptor,
however, no evidence for the alpha1B- and alpha1D-adrenergic receptor was found.
Further, analysis of RNA extracted from blood, which was a contaminant of the
microdissected spiral modiolar arteries, revealed no RT-PCR products. Sequence
analysis of the RT-PCR product of the alpha1A-adrenergic receptor from the spiral
modiolar artery confirmed its identity. Identity between the 175 nt gerbil
sequence fragment and the known rat, mouse and human alpha1A-adrenergic receptor
sequences was 90.9, 92.0 and 85.2%, respectively. These observations demonstrate
that the spiral modiolar artery contains alpha1A-adrenergic receptors which
mediate vasoconstriction at branch points.
PMID- 9641325
TI - Detection of transcripts for delayed rectifier potassium channels in the Xenopus
laevis inner ear.
AB - Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify
sequences for delayed rectifier potassium (drk) channel transcripts in Xenopus
laevis inner ear and brain. We used degenerate primers that spanned a region
between the N-terminal cytoplasmic portion and a region located between the S2
and S3 transmembrane domains of the potassium channel protein. When inner ear
total RNA or brain mRNA was used as a template for RT-PCR, a unique product of
the expected size (approximately 560 bp) was observed as a single band after
electrophoresis on agarose gels. The PCR product from reactions using X. laevis
genomic DNA as template was similarly sized, indicating a lack of introns in this
region. The RT-PCR products from inner ear and brain were isolated, cloned, and
sequenced. Sequence analysis showed that the X. laevis inner ear and brain clones
were identical. Sequence alignments of the cloned RT-PCR products with posted
GenBank sequences established that the drk sequences from X. laevis inner ear and
brain share highest identity with larval X. laevis brain, mouse, rat, and human
Kv2 sequences. Positive signals were obtained from inner ear and brain mRNA in
Northern dot blots hybridized with digoxigenin labeled probes from the inner ear
clone. Taken together, results provide evidence for the expression of Kv2
sequences in the X. laevis inner ear and brain.
PMID- 9641326
TI - Threshold-duration functions of chinchilla auditory nerve fibers.
AB - The purpose of the present study was to measure the change in threshold as a
function of stimulus duration in single auditory nerve fibers. Thresholds were
measured at each neuron's characteristic frequency (CF) for eight stimulus
durations ranging from 8 to 1024 ms. Using an adaptive, two-interval, forced
choice threshold-tracking procedure with a 2-down, 1-up rule, thresholds were
estimated based on a decision criterion of one spike or greater difference
between tone and no-tone intervals. The results showed that mean thresholds
decreased with increasing stimulus duration by approximately 14.6 dB over the
range of durations tested. Analysis of group and individual data showed that
thresholds decreased by approximately 6-7 dB per decade of duration. The slope of
threshold improvement decreased systematically with increasing CF, consistent
with previous physiological and psychophysical data.
PMID- 9641328
TI - Basic response characteristics of auditory nerve fibers in the grassfrog (Rana
temporaria).
AB - Responses to free-field sound of 401 fibers from the VIIIth nerve of the
grassfrog, Rana temporaria, are described. The spontaneous activities of the
fibers ranged from 0 to 75 spikes/s, showing only weak correlation with frequency
or sensitivity of the fibers. The highest spontaneous activities were
approximately twice as high as reported previously for frogs. Best frequencies
ranged from 100 to 1600 Hz and thresholds ranged from 21 to 80 dB SPL. The median
dynamic range was 20 dB and the slopes of the rate-level curves ranged from 5 to
20 spikes/(s-dB). Most of the units showed post-excitatory suppression (PS) of
their spontaneous activity. The duration of PS increased with sound level, also
in fibers showing a decrease in firing rate at high intensities. Most fibers
showing one-tone suppression did not show PS at their best suppression
frequencies. Strong suppression was observed also in very phasic cells giving one
spike per stimulation. Therefore, the mechanism underlying PS is probably
different from that underlying adaptation. The sharpening of the neural encoding
of temporal parameters and the strong encoding of sound offset as well as onset
caused by PS very likely is biologically important.
PMID- 9641327
TI - Electrically evoked compound action potentials of guinea pig and cat: responses
to monopolar, monophasic stimulation.
AB - We recorded electrically evoked compound action potentials (EAPs) from guinea
pigs and cats using monophasic current pulses delivered by a monopolar
intracochlear electrode. By using simple stimuli, we sought results that could
shed light on basic excitation properties of the auditory nerve. In these acute
experiments, the recording electrode was placed directly on the auditory nerve.
Responses to anodic and cathodic stimulus pulses were recorded separately to
evaluate stimulus polarity effects. Several polarity-dependent properties were
observed. Both EAP morphology and latency were polarity-dependent, with greater
latencies for cathodic stimulation. Threshold stimulus level was also polarity
dependent, but in different directions in the two species: cats had lower
cathodic thresholds while guinea pigs had lower anodic thresholds. We also
observed that the slopes of the EAP amplitude-level functions depended upon
stimulus polarity. In most cases where EAP saturation amplitude could be
measured, that amplitude was similar for anodic and cathodic stimuli, suggesting
that either stimulus polarity can recruit all fibers, or at least a comparable
numbers of fibers. The common findings (e.g., EAP morphology and polarity
dependent latency) observed in these two species suggest results that can be
extrapolated to responses obtained in humans, while the species-specific findings
(e.g., dependence of threshold on polarity) may point to underlying anatomical
differences that caution against overgeneralization across species. Some of our
observations also bear upon hypotheses of how electrical stimuli may excite
different sites on auditory nerve fibers.
PMID- 9641329
TI - Partial left ventriculectomy and mitral valve repair for end-stage congestive
heart failure.
AB - OBJECTIVE: Partial left ventriculectomy (PLV), pioneered by Batista, has been
proposed as an alternative treatment strategy in patients with refractory
congestive heart failure. In order to analyze the midterm outcome of PLV and
mitral valve (MV) repair and stratify patients according to risk, we
prospectively studied 57 consecutive patients who underwent this procedure at the
Cleveland Clinic Foundation (CCF). METHODS: Patients had a mean age of 53 years
and were predominantly males (74%). In 95% the etiology of heart failure was
idiopathic dilated cardiomyopathy. All patients had a left ventricular end
diastolic diameter of >7cm and were in New York Heart Association (NYHA)
functional classes III and IV. A total of 54 patients (95%) were awaiting heart
transplantation. Preoperatively, requirements included inotropes in 23 (40%),
intraaortic balloon pump counterpulsation in 3 (5.3%), and left ventricular
assist device placement (LVAD) in 1 (1.8%). Concomitant procedures included MV
repair (55 patients), MV replacement (2), tricuspid valve repair (34 patients),
coronary artery bypass graft (CABG) (5), and aortic valve repair or replacement
(1 patient each). RESULTS: Measurements preoperatively and at 3 months
demonstrated improvement in left ventricular ejection fraction (14.4 +/- 7.7-23.2
+/- 10.7%, P < 0.001), left ventricular end diastolic volume (254 +/- 85-179 +/-
73 ml, P < 0.001) and left ventricular end diastolic diameter (8.4 +/- 1.1-6.3 +/
0.9 cm, P < 0.001). Peak oxygen consumption (MVO2) increased from 10.6 +/- 3.9
to 15.3 +/- 4.5 ml/kg per min (P < 0.001). Cardiac index did not change (2.2
l/min per m2), although 40% had been on inotropes preoperatively and none were on
inotropes at 3 months. NYHA functional class improved from 3.6 +/- 0.5
preoperatively to 2.2 +/- 0.9 at 3 months (P < 0.001). LVAD support was required
as rescue therapy in 11 patients (17%). Actuarial freedom from procedure failure,
defined as death or relisting for transplant, was 58% at 1 year. Hospital
mortality was 3.5% (n = 2). On follow-up, there were 7 late deaths (including 3
sudden deaths) giving an actuarial survival of 82% at 1 year. Multivariate risk
factor analysis revealed that age less than 40 years was associated with failure
(P = 0.02). CONCLUSIONS: Although PLV with MV repair is now a surgical option in
the treatment of end-stage congestive heart failure, caution is advised as early
failures are unpredictable and mechanical support may be required as rescue
therapy. Better risk stratification and patient selection may improve outcome.
Further study is required to determine the procedure's exact role in the
treatment of congestive heart failure.
PMID- 9641330
TI - High-risk mitral valve replacement in severe pulmonary hypertension--30 years
experience.
AB - OBJECTIVE: In the past 30 years, 2316 patients underwent mitral valve replacement
(MVR) at our institution; 382 of them had severe pulmonary hypertension
(pulmonary artery pressure (PAP) > 50 mmHg; pulmonary vascular resistance (PVR),
690 +/- 46 dyn/s per m2). We reviewed our early and late results in this high
risk subgroup. METHODS: We used 336 mechanical and 46 biological devices for MVR.
The follow-up was 95%, with an observation period of 3208 patient-years and a
mean of 8.4 +/- 0.2 years per patient. The overall early mortality rate was 10.5%
(n = 40) and stayed at about the same level over the years, although patients
characteristics have changed to much older patients and more reoperations. To
clarify this fact we divided our data in results according to the decades in
which the operations were carried out. The clinical preoperative status and
results were as follows (*P < 0.05; **P < 0.01 compared with previous decade). In
the decades between 1963 and 1973 (I), 1974 and 1983 (11) and 1984 and 1993 (III)
we operated on n = 95 (I), n = 185 (II), and n = 102 (III) patients with a mean
age of 43 +/- 1 (I), 50 +/- 1** (II), and 58 +/- 1** (III) years. The incidence
of reoperations among these patients was 3.2 (I), 4.9 (II), and 22.6%** (III).
The early mortalities were 13.7 (I), 8.6* (II) and 10.8% (III); late mortalities
lowered from 5.77 (I), over 4.95 (II), and up to 3.39%** (III) patients/year. The
mean functional status according to New York Heart Association (NYHA) class
improved from preoperatively 3.0 +/- 0.1 (I), 3.2 +/- 0.1 (II) and 3.3 +/- 0.1
(III) to 2.4 +/- 0.2 (I), 2.4 +/- 0.1 (II) and 2.3 +/- 0.1 (III) postoperatively.
RESULTS: Compared with routine elective MVR with a mortality rate of 3.6% (P <
0.01), early mortality is high. But once the patient survives the perioperative
course, late results show no difference compared with patients without pulmonary
hypertension. The functional results as well are not significantly different. In
spite of on average 15 years older multimorbid patients with therefore higher
complication rates, early results improved slightly, which could be explained by
better operative techniques, perioperative treatment and nursing (online
monitoring with immediate therapeutic substitution). Surprisingly the increased
number of reoperations had no negative impact on patients' outcomes. CONCLUSION:
According to our results, we recommend MVR in severe pulmonary hypertension even
in the elderly, with a high but acceptable risk and good long-term results.
PMID- 9641331
TI - A comparative study of structures comprising the thoracic outlet in 250 human
cadavers and 72 surgical cases of thoracic outlet syndrome.
AB - OBJECTIVE: We have hypothesized that variations in fibrous, muscular and osseous
structures with the potential to entrap the brachial plexus occur within the
thoracic outlet of the normal population; and that these variations are different
in pattern and frequency from those in patients presenting with thoracic outlet
syndrome (TOS). METHODS: Structural anomalies with potential for entrapping
elements of the brachial plexus were examined following dissections of the
posterior triangle of the neck in 250 human cadavers (N = 500 thoracic outlet
dissections) and catalogued jointly by an anatomist and a thoracic surgeon. The
pattern and frequency of anomalies in the 250 cadavers was compared to that
encountered in 72 surgical cases of removal of the first rib for relief of
symptomatic TOS (N = 72 procedures, 55 patients). RESULTS: Relevant structural
variations were encountered in 46% of cadavers, exhibiting no left right or
gender preference overall. When compared with the surgical group in which 100%
exhibited structurally relevant anomalies, significant differences in pattern of
anomalous structures and gender distribution were revealed. Anomalies posterior
to the brachial plexus, ranging from fibrous bands to cervical ribs in both
groups, were prevalent in the surgical group. A 'scissors-like' pattern, with
neural entrapment by anterior and posterior anomalies was frequently encountered
in females. CONCLUSIONS: Based on these data and embryological considerations, we
propose a revised and simplified classification of impingement mechanisms within
the anatomic thoracic outlet. Comparing these data to radiological imaging and
observations at surgery, we offer a new perspective for the investigation and
management of patients with TOS.
PMID- 9641332
TI - Technique to reduce air leaks after pulmonary lobectomy.
AB - OBJECTIVE: Patients undergoing pulmonary resections often present postoperative
air leaks of varying magnitude and duration; this complication is more frequent
with incomplete or absent interlobar fissures. Small leaks close spontaneously
within 5-7 days; larger leaks may persist longer and could be associated with
increased morbidity and prolonged hospitalization. We evaluated the role of
different techniques to complete interlobar fissures before pulmonary lobectomy
to prevent postoperative air leaks and reduce hospital stay and costs. METHODS: A
total of 30 patients undergoing pulmonary lobectomy for lung cancer and
presenting incomplete interlobar fissures that needed to be opened both
anteriorly and posteriorly were randomized into three groups. In Group I,
fissures were created with a GIA stapler and buttressed with bovine pericardial
sleeves. In Group II, we used TA 55 staplers alone; in Group III we used the 'old
fashion' cautery, clamps and silk ties. The three groups were homogeneous for
age, type of pulmonary resection and stage of the tumor. The duration of
postoperative air leaks and hospital stay were compared with the one-way variance
analysis. RESULTS: Postoperative air leaks for Groups I, II and III persisted for
2 +/- 0.94, 5.3 +/- 2 and 5.3 +/- 1.7 days, respectively. Mean hospital stay was
4.4 +/- 0.96, 7.8 +/- 2.14 and 7.2 +/- 1.5, respectively. The difference between
groups in terms of duration of postoperative air leaks and hospital stay was
statistically significant (P = 0.0001). CONCLUSIONS: The use of GIA staplers and
pericardial sleeves to complete interlobar fissures for pulmonary lobectomy
significantly reduces the duration of postoperative air leaks and hospital stay;
no complications were associated with this technique.
PMID- 9641333
TI - Coronary bypass surgery: what is changing? Analysis of 3834 patients undergoing
primary isolated myocardial revascularization.
AB - OBJECTIVE: The patient population undergoing myocardial revascularization has
changed during the last few years. Knowledge of these changes, and of the
subsequent influence on morbidity and/or mortality is important, not only for up
dating quality control, but also to support decision-making in financial and
economical aspects, and in further research concerning coronary artery surgery.
METHODS: Pre-, per- and postoperative data of 3834 primary isolated coronary
bypass operations, January 1987 December 1995 were analyzed. The total group was
divided into three time cohorts. Group A: 1987 1989 (n = 1292); group B: 1990
1992 (n = 1130); and group C: 1993-1995 (n = 1412). RESULTS: Mean age increased
from 60.4 +/- 9.0 (S.D.) years in group A to 62.9 +/- 9.9 (S.D.) years in group C
(P < 0.0005). Patients with insulin-dependent diabetic (P = 0.005), uro
nefrological (P = 0.002), pulmonary (P < 0.0005)and neurological (P = 0.003)
pathology increased significantly, and there was a significant increase in the
use of arterial grafts (P < 0.05). Postoperative, hospital mortality remained
stable (+/- 2.5%). However, there was a significant increasing percentage of
patients with pulmonary (P = 0.04), neurological (P = 0.02) and uro-nefrological
(P < 0.0005) problems. CONCLUSION: During the last few years there has been a
trend in myocardial revascularization of older patients, with more coexisting
disease. Despite the fact that hospital mortality seems stable, there is an
increase in major postoperative morbidity.
PMID- 9641334
TI - Cerebral oxygenation during paediatric cardiac surgery: identification of
vulnerable periods using near infrared spectroscopy.
AB - OBJECTIVE: Neurologic sequelae remain a well recognised complication of
paediatric cardiac surgery. Monitoring of cerebral oxygenation may be a useful
technique for identifying vulnerable periods for the development of neurologic
injury. We sought to measure regional cerebral oxygenation in children undergoing
cardiac surgery using near infrared spectroscopy to ascertain such vulnerable
periods. METHODS: Observational study of 18 children (median age 1.3 years)
undergoing cardiac surgery (17 with cardiopulmonary bypass, 8 with circulatory
arrest). Regional cerebral oxygenation was monitored using the INVOS 3100
cerebral oximeter and related to haemodynamic parameters at each stage of the
procedure. RESULTS: Prior to the onset of bypass, 10 patients had a decrease in
regional cerebral oxygenation of > or = 15% points, reaching an absolute
haemoglobin saturation less than 35% in 5 cases. The most common cause was
handling and dissection around the heart prior to and during caval cannulation.
With institution of bypass, regional cerebral oxygenation increased by a mean 18%
points to a mean maximum of 75%. During circulatory arrest regional cerebral
oxygenation decreased with rate of decay influenced by temperature at onset of
arrest (0.25%/min at < 20 degrees C; 2%/min at > 20 degrees C). Reperfusion
caused an immediate increase in regional cerebral oxygenation followed by a
decrease during rewarming. Discontinuation of bypass caused a precipitous
decrease in regional cerebral oxygenation in 5 patients, reaching less than 50%
in 3 patients. CONCLUSIONS: These observations suggest that the pre- and early
post-bypass periods are vulnerable times for provision of adequate cerebral
oxygenation. Near infrared spectroscopy is a promising tool for monitoring O2
supply/demand relationships especially during circulatory arrest.
PMID- 9641335
TI - Cardiac troponin I as an early marker of myocardial damage after coronary bypass
surgery.
AB - STUDY OBJECTIVE: To evaluate the performance of cardiac specific markers, cardiac
troponin I (cTnI) and CK-MB by mass assay (CK-MB mass), for the early diagnosis
of myocardial ischemia and/or infarction after coronary bypass surgery. METHODS:
Prospective clinical, electrocardiograpic and biologic follow-up of 117 patients
undergoing isolated coronary surgery with the use of intermittent anterograde
normothermic blood cardioplegia. Blood samples for biochemical analysis were
drawn before surgery (T0) and at 2 (T1), 6 (T2), 10 (T3) and 20 h (T4) after
aortic cross-clamp release. Without knowledge of the biochemical data, patients
were classified according to the electrocardiographic evolution into two groups:
group 1, uneventful recovery and group 2, evidence of ischemia/infarction based
on continuous ST-T segment monitoring and 12-lead ECG. RESULTS: No patients had
abnormal markers at T0. At T1, although both markers were elevated, no difference
was noted between the two groups. At T2, 6 h after surgery, cTnI and CK-MB mass
levels were significantly higher in group 2 than in group 1 (median = 17
microg/l, Interquartile Range (IR): 14.7-27.3 vs. 3.1 microg/l, IR 1.9-5.3 for
cTnI and median 42.5 microg/l, IR: 27.1-95.7 vs. 13.6 microg/l, IR: 9.5-18.5 for
CK-MB mass). A receiver operating characteristic (ROC) curve analysis shows that
a cTnI value of 13.1 microg/ml has 100% specificity and 90% sensitivity to
separate both groups, whereas a value of 33.2 microg/ml for CK-MB mass has a
specificity of 100% and a sensitivity of 73%. At T3 and T4, the same difference
was noted between the groups. cTnI values in all six patients with a Q-wave
infarction were > or = 20 ng/ml, whereas only one of five patients with prolonged
ischemia had cTnI level > 20 ng/ml. CONCLUSION: As soon as 6 h postoperatively,
cTnI and CK-MB by mass assay were able to separate those patients with an
uneventful recovery from those with significant ischemia. This is particularly
useful in frequent cases when the ECG is difficult to interpret.
PMID- 9641336
TI - von Willebrand factor and urinary albumin excretion are possible indicators of
endothelial dysfunction in cardiopulmonary bypass.
AB - OBJECTIVE: Experimental evidence suggests that cardiopulmonary bypass (CPB)
associated inflammatory response leads to endothelial injury and increased
permeability, but this has been difficult to show clinically. We have
investigated the use of von Willebrand factor (vWF), and urinary albumin
excretion, as measured by the urinary albumin creatinine ratio (ACR), to
demonstrate this. METHODS: A total of 23 patients undergoing elective coronary
artery bypass grafting were studied. Complement fragment C3a, leukotrienne B4
(LTB4), interleukin 6 (IL6), neutrophil elastase, vWF and ACR were measured on
anaesthetic induction (baseline), 20 min after starting CPB, 5 min after cross
clamp removal, 5 min, 2, 6 and 24 h after termination of CPB. Anaesthetic, CPB
and myocardial protection techniques were standardised. ANOVA was performed by
using the distribution free Friedman test for each measured parameter. When
significance differences were found (P < 0.05), post hoc analysis with Wilcoxon
signed rank test was used for comparison of each time point with the base line
level and differences were only accepted as significant following the Bonferroni
correction (P < 0.008). Summary measures of peak versus peak and area under the
cure were also analysed for ACR with vWF. RESULTS: Peak vs. baseline levels for
C3a were 4.9 vs. 2.1 microg/ml (P < 0.0001), LTB4 was 800 vs. 20 pg/ml (P <
0.0001), neutrophil elastase was 250 vs. 115 ng/ml (P < 0.001), IL6 was 620 vs.
1.4 pg/ml (P < 0.0001), vWF was 2.2 vs. 1.3 IU/ml (P < 0.0001) and ACR was 17.6
vs. 2.0 mg/mmol (P < 0.0001). C3a, LTB4 and ACR peaked during the operation.
Neutrophil elastase peaked at 2 h following CPB. IL6 and vWF peaked at 6 h
following CPB. The correlation coefficient between vWF and ACR following peak
versus peak analysis was 0.48 (P = 0.035), and area under the curve analysis was
0.6 (P < 0.01). CONCLUSION: These results demonstrate that endothelial
permeability and injury, as measured by urinary albumin excretion and vWF,
respectively, are related and the use of these easily detectable and sensitive
biochemical markers warrants further investigation.
PMID- 9641337
TI - Transmyocardial laser revascularization using the Holium-YAG laser for treatment
of end stage coronary artery disease.
AB - OBJECTIVE: Transmyocardial Laserrevascularization (TMLR) is a treatment for end
stage coronary artery disease, that is not eligible for surgery or PTCA. The
experience with TMLR using the Holium YAG laser is presented. METHODS:
Transmyocardial Laserrevascularization (TMLR) was performed in 28 patients with
end stage coronary artery disease, using a new Holium YAG Laser. All patients
were refractory to a maximum of medical treatment. In 16 patients TMLR was used
as the sole therapy with a mean of 28 +/- 4 laser created channels (group A). In
12 patients TMLR was combined with coronary artery bypass graft surgery with a
mean of 17 +/- 2 channels and 1.3 +/- 0.2 grafts (group B). Preoperative and
postoperative examination included angina classification, exercise test and
thallium scan. RESULTS: Postoperative demographics were as follows: (a) age 55-71
years (mean 63.9 +/- 6.5 years); (b) Canadian Cardiovascular Society Angina Scale
(CCS) mean 3.3 +/- 0.5; (c) ejection fraction 35-71% (mean 54 +/- 13.7%). All
patients had an peri- and postoperative course without major complications and a
duration of hospitalization of 8.2 +/- 1.9 days. Minor complications were a
clinically silent myocardial infarction n = 1, atrial arrhythmia n = 2 and
pneumothorax n = 2. A follow-up at 3-12 months was completed in 23 patients
(82%). Only one patient died 5 months after surgery (cardiac related death). In
all remaining patients CCS had improved with a mean of 1.6 +/- 0.3, P < 0.01. The
exercise tolerance test (bicycle) improved in 17 patients with a mean 26.5 +/-
6.5 watt, P < 0.01. The ejection fraction did not significantly improve. The
repeated thallium scan did not show an improvement of perfusion in the lasered
area to a significant level. Subjective benefit from the treatment was confirmed
by 21 patients. CONCLUSION: Based on these results it is concluded that TMLR with
the Holium-YAG laser is a safe therapy for the treatment of end stage coronary
artery disease. The postoperative clinical results are comparable to that
achieved with the CO2-laser in terms of reducing angina symptoms and improving
exercise tolerance and quality of life. However. relief of symptoms is not
correlated to objective findings of cardiac function.
PMID- 9641338
TI - Electron-microscopic findings after transmyocardial laser revascularization in an
acute ischemic pig model.
AB - OBJECTIVE: The clinical benefit in terms of angina reduction after
transmyocardial laser revascularization (TMLR) in patients with diffuse coronary
artery disease who are not candidates for conventional procedures has been
proved. The exact mechanisms of TMLR however, are still unknown. The aim of this
study was to investigate the cellular changes in relation to intramyocardial
partial oxygen pressure (ptiO2) after TMLR in a model of acute ischemia in pigs
by electron microscopical methods (TEM). METHODS: Seven pigs were included in
this study (five animals with acute myocardial ischemia and additional TMLR and
two animals with acute myocardial ischemia and without TMLR for control). Acute
ischemia was induced by ligation of diagonal branches of the left anterior
descending artery (LAD). Intramyocardial partial oxygen pressure was measured
before induction of ischemia and thereafter continuously for up to 6 h in all
animals. Biopsies of all animals were taken before induction of ischemia and
thereafter at 30 min, 3 and 6 h. Analysis of the myocardial ultrastructure was
focused on mitochondria, cell nucleus, T-tubules and myofibrils. RESULTS:
Ultrastructural changes were seen in all animals. At 6 h after induction of
ischemia, mitochondria showed a destruction of the internal as well as the
external membrane and of the cristae. The nuclei showed margination of the
chromatin. Myofibrils were characterized by ruptures in the Z-stripes. Lipid
droplets as an indicator of ischemia could be identified. PtiO2 between 40 and 80
mmHg before intervention decreased down to 0-2 mmHg within the first 9 min after
diagonal branch ligation and did not increase even after TMLR. CONCLUSIONS: In
this acute ischemic model using pigs, TEM evaluation following TMLR proves
irreversible changes of the myocardial ultrastructure. Furthermore, TMLR was not
able to increase ischemically induced decrease of ptiO2. These data provide some
evidence that TMLR thus, may not be able to ameliorate acute ischemia at least in
the pig model. Further investigations are needed to investigate the effect of
TMLR in chronic myocardial ischemia.
PMID- 9641339
TI - Non-invasive evaluation of mammary artery flow reserve and adequacy to increased
myocardial oxygen demand.
AB - OBJECTIVE: To evaluate the flow reserve and adequacy to meet myocardial requests
in stress conditions of mammary artery-left anterior descending (IMA-LAD) grafts
using a non-invasive method. METHODS: Patients (20) with angiographic evidence of
normofunctioning left IMA-LAD grafts were submitted to dypiridamole Tl201
myocardial scintigraphy and concomitant transthoracic echo-doppler evaluation of
the IMA flow at a mean interval of 32.5 months after surgery. RESULTS: Under
basal conditions, the mean peak and end flow velocities in systole were 0.39 and
0.06 m/s, respectively. In diastole, the mean peak and end flow velocities were
0.27 and 0.02 m/s and mean tele-diastolic flow velocity was 0.14 m/s, with a mean
systolic/diastolic ratio of 1.51. After dypiridamole infusion, mean systolic
velocities were 0.47 (peak) and 0.23 (end) m/s, respectively + 20 and + 283%,
whereas mean diastolic velocities were 0.56 (peak) and 0.06 (end) m/s, +107 and
+200%, respectively. Mean tele-diastolic flow velocity increased to 0.32 m/s
(+128%) and the systolic-diastolic index changed to 0.85. In all cases no
significant scintigraphic evidence of induced ischemia was demonstrated in the
LAD region. CONCLUSIONS: Transthoracic echo-doppler evaluation combined with
Tl201 myocardial scintigraphy is a useful tool for the assessment of IMA flow
reserve and adequacy to stress conditions. In the late postoperative period, the
IMA shows the possibility of increasing the flow velocity, almost 2-fold; the
increase in flow is prevalently diastolic and leads to a complete reversal of the
physiological systolic/diastolic flow ratio. The flow reserve of IMA is always
able to meet the augmented myocardial oxygen demand after dypiridamole infusion.
PMID- 9641340
TI - Endothelium-dependent and endothelium-independent flow reserve in vascular
regions supplied by the internal mammary artery before and after bypass grafting.
AB - OBJECTIVE: It was the goal of this study to compare endothelium-dependent and
endothelium-independent flow reserve in vascular regions supplied by the left
internal mammary artery before and after bypass graft surgery. METHODS: The
native internal mammary artery in situ was investigated in 13 patients (age 61.8
+/- 8.0 years) with angiographically proven coronary artery disease. The internal
mammary artery after bypass grafting was investigated in ten patients (age 60.8
+/- 7.3 years) 3.5 +/- 2.8 years after the operation. Flow reserve was evaluated
endothelium-dependent with acetylcholine (ACh 25 and 50 microg i.c.) and
endothelium-independent with nitroglycerin (NTG 0.3 mg i.c.) followed by
papaverin (10 mg i.c.). Flow indices were calculated from intraluminal Doppler
blood flow velocity measurements and the vascular cross-sectional area as
determined by quantitative angiography. An index for vascular resistance was
defined as the ratio of pressure gradient and resting or peak flow. RESULTS:
After endothelium-dependent stimulation with acetylcholine 25 microg (50 microg),
flow in the internal mammary increased by 352.3 +/- 152% (412 +/- 145%) before
surgery, whereas it increased only by 213 +/- 134% (193 +/- 120%) after surgery
(P < 0.05). Endothelium independent stimulation with papaverin resulted in a flow
increase of 391 +/- 234% before surgery vs. 315 +/- 135% after surgery (n.s.).
The resistance index decreased after endothelium-dependent stimulation with
acetylcholine 25 microg(50 microg) to 35 +/- 16.8% (28 +/- 8.9%) before surgery,
whereas it decreased only to 59 +/- 26% (72 +/- 43%) after surgery (P < 0.05).
Endothelium independent stimulation with papaverin resulted in a decrease of the
vascular resistance index to 31 +/- 14% before surgery vs. 32 +/- 14% after
surgery (n.s.). CONCLUSION: Vascular regions supplied by the internal mammary
artery as a graft demonstrate a significantly reduced endothelium-dependent flow
reserve but a preserved endothelium-independent flow reserve as compared to
vascular regions supplied by the native internal mammary artery. The selective
decrease in endothelium-dependent flow reserve may be due to microvascular
changes in the myocardial region supplied by the internal mammary artery after
bypass grafting.
PMID- 9641341
TI - Long-term prognosis of surgically-treated aortic aneurysms and dissections in
patients with and without Marfan syndrome.
AB - OBJECTIVE: Aortic aneurysms and dissections are the leading causes of premature
death in Marfan syndrome (MfS). This study aims to compare long-term results of
surgically treated aortic aneurysms and dissections in patients with and without
MfS in respect to early and late prognosis. METHODS: From March 1975 to August
1994, 33 patients with classic MfS (group A, age 34.2 +/- 9 years) and 298
patients with non-fibrillinopathic aortic disease (group B, age 54 +/- 13 years)
underwent aortic surgery. Acute dissections occurred in 57.6 (A) versus 37.9%
(B). A total of 54.6% of patients in group A were treated with a composite graft
versus 16.4% in B. The aortic arch and the descending aorta was replaced in 30.4%
of MfS patients and 24.9% of patients without MfS. RESULTS: We observed 7 (25.0%,
A) versus 35 (14.2%, B) late deaths among the 28 (A) versus 247 (B) early
survivors. In 5 patients (17.9%) of A and 8 patients (3.2%) of B, late death was
caused by redissection or recurrent aneurysm (P < 0.001). Long-term survival
after 5, 10 and 15 years in group A was 82 +/- 7, 60 +/- 11 and 30 +/- 22%, and
75 +/- 3, 69 +/- 3 and 64 +/- 4% in group B. A total of 22 reoperations were
performed in 11 MfS patients, 17 reoperations were due to recurrent aortic
diseases. Three of the 8 patients underwent reoperation after Wheat procedure
because of sinus valsalva aneurysm. None of the patients with composite graft
replacement needed reoperation in this segment, but 3 patients suffered from
redissection at the proximal aortic arch. In group B, reoperations were
significantly less frequent (10.7%) compared to MfS patients (66.7%; P < 0.001).
CONCLUSIONS: Surgical treatment of aortic disease in MfS patients is associated
with a high risk of redissection and recurrent aneurysm. If the ascending aorta
needs to be replaced, we recommend the composite graft technique and a more
aggressive approach to reduce the frequency of distal reoperations. In order to
reduce the high reoperation rate in MfS patients, frequent clinical follow-up may
contribute to improve life expectancy in MfS patients.
PMID- 9641342
TI - Transforming growth factor-beta1 and lung allograft fibrosis.
AB - OBJECTIVES: Transforming growth factor beta1 (TGF-beta1) is a potent
immunosuppressive cytokine that promotes fibrosis by enhancing the synthesis of
extracellular matrix components. The repair process following lung allograft
injury is due to rejection or infection replaces lung parenchyma by fibrotic
tissue, leading to pulmonary dysfunction. The role of TGF-beta1 in this excessive
healing process and increasing the risk of infection is unknown. METHODS: We
analysed our patient data to investigate the relevance of different factors on
allograft fibrosis and its correlation with TGF-beta1. Fibrosis was graded in H
and E stained sections. TGF-beta1 genotype was determined in all patients.
RESULTS: Patients were aged between 16 and 62 years (mean age of 39.6 years).
Procedures were heart/lung (n = 32), double lung (n = 18), and SLT (n = 41). A
total of 46 patients had lung allograft fibrosis diagnosed in transbronchial
biopsies sections. Patients who had developed interstitial fibrosis had
significantly more acute rejection episodes (mean 3.4 +/- 2.8) compared with
patients without fibrosis (mean 2.1 +/- 2.2) (P = 0.024). The presence of
eosinophils in the interstitium preceded and were associated with the development
of fibrosis regardless of the rejection grade (P = 0.0001). TGF-beta1 was heavily
expressed in sections with fibrosis with a mean score of 6.8 +/- 2.9 compared
with 2.4 +/- 0.6 in sections with no fibrosis (P < 0.0001). TGF-beta1 expression
correlated positively with fibrosis grades (P < 0.0001). The mean survival for
patients with a fibrosis score > 6 is 892.4 +/- 73 days compared with mean
survival 427 +/- 78 in patients with scores < 6 (P = 0.0001). Patients who
developed fibrosis had homozygous TGF-beta1 genotype that correlates with
excessive TGF-beta1 expression (P = 0.01). The use of cardiopulmonary bypass was
associated with the development of excessive fibrosis (P = 0.02), and 7 patients
who had severe fibrosis died of septicaemia (17.5%). FEV1 (forced expiratory
volume) was significantly higher in patients without fibrosis (1870 +/- 111 ml
versus 1590 +/- 160; P = 0.02). CONCLUSIONS: The risks of lung allograft fibrosis
increases with recurrent rejection, tissue eosinophilia, homozygous TGF-beta1
genotype and the use of bypass machine. Fibrosis was associated with higher
mortality and morbidity might be explained by the TGF-beta1 immunosuppressive and
fibrotic properties. Immunological strategies to down-regulate TGF-beta1
production might improve survival and function of lung allografts.
PMID- 9641343
TI - Alveolar expansion itself but not continuous oxygen supply enhances postmortem
preservation of pulmonary grafts.
AB - OBJECTIVE: If lungs could be retrieved for transplant after circulatory arrest,
the shortage of donors might be significantly alleviated. Great controversy still
exists concerning the optimal mode of preservation of pulmonary grafts in these
non-heart-beating donors. METHODS: Graft function was measured in an isolated
room air-ventilated rabbit lung model during reperfusion with homologous, diluted
(Hb +/- 8.0 g/dl) and deoxygenated (PaO2 +/- 40 mmHg) blood up to 4 h. Five
groups of cadavers (n = 4 in each group) were studied: In the control group,
lungs were immediately reperfused. In the other groups, cadavers were left at
room temperature for 4 h after death with lungs either deflated (group 1),
inflated with room air (group 2), or ventilated with room air (group 3) or 100%
nitrogen (group 4). RESULTS: After 1 h of reperfusion, significant differences
were noted between group 1 and groups 2, 3, and 4 in peak airway pressure (27 +/-
5 cm H2O vs. 15 +/- 1 cm H2O, 17 +/- 2 cm H2O, and 16 +/- 1 cm H2O, respectively;
P < 0.05), in weight gain (137 +/- 24 vs. 31 +/- 7, 30 +/- 3, and 30 +/- 2%,
respectively; P < 0.05), and in veno-arterial oxygen pressure gradient (9 +/- 5
vs. 95 +/- 13, 96 +/- 7 and 96 +/- 4 mmHg, respectively; P < 0.05). Also, wet-to
dry weight ratio at end of reperfusion was significantly different (10.2 +/- 1.0
vs. 6.0 +/- 0.3. 5.2 +/- 0.3 and 5.4 +/- 0.5, respectively; P < 0.05). No
significant differences in any of these parameters were observed between groups
2, 3, and 4. CONCLUSIONS: These data suggest that: (1) pulmonary edema will
develop in atelectatic lungs if reperfusion is delayed for 4 h after death; (2)
postmortem room air-inflation is as good as ventilation in prolonging warm
ischemic tolerance; (3) ventilation with room air is no different from that with
nitrogen; (4) therefore, prevention of alveolar collapse appears to be the
critical factor in protecting the warm ischemic lung from reperfusion injury
independent of continuous oxygen supply.
PMID- 9641344
TI - Effect of a short period of warm ischemia after cold preservation on reperfusion
injury in lung allotransplantation.
AB - OBJECTIVE: A short period of warm ischemia during lung allograft implantation is
inevitable. We studied the effect of 2 h of warm ischemia before implantation
after 18 h of cold preservation on reperfusion edema and pulmonary hemodynamics
in a large animal model. METHODS: Left lung transplantation was performed in ten
weight-matched pigs (25-31 kg). Donor lungs were flushed with 1.5 l cold (1
degree C) LPD solution and preserved for 20 h. In Group I (n = 5) the grafts were
preserved for 20 h at 1 degree C and topically cooled with ice slush during
implantation until reperfusion. In Group II (n = 5) lungs were stored at 1 degree
C for 18 h followed by 2 h preservation at room temperature (20 degrees C).
Topical cooling was not used during implantation. At 1 h after reperfusion the
recipient contralateral right pulmonary artery and bronchus were ligated to
assess graft function only. Extravascular lung water index (EVLWI), intrathoracic
blood volume (ITBV), mean pulmonary artery pressure (PAP) and cardiac output (CO)
were assessed during a 4 h observation period. Quantitative myeloperoxidase (MPO)
activity and thiobarbituric acid-reactive substance (TBARS) levels as an
indicator for lipid peroxidation were determined in allograft tissue samples
taken 5 h after reperfusion. RESULTS: In Group II a tendency to improved
pulmonary vascular resistance and cardiac output was noted. Surprisingly, lung
edema, assessed by EVLWI, did not increase in animals with warm ischemia. Even a
tendency to a reduced EVLWI was noted. However, differences between groups did
not reach statistical significance. Gas exchange did not differ statistically
significant between groups. CONCLUSION: Our results indicate that a short period
of warm ischemia before reperfusion does not lead to increased pulmonary edema.
In animals with a short period of warm ischemia before reperfusion, even a
tendency to reduced posttransplant lung reperfusion injury was noted. In this
model, topical graft cooling during lung implantation did not improve
posttransplant graft function.
PMID- 9641345
TI - Right ventricular function after brain death: response to an increased afterload.
AB - OBJECTIVE: A major cause of early postoperative morbidity and mortality after
cardiac transplantation is right ventricular (RV) failure which is attributed to
the inability of the donor's RV to acutely compensate for the recipient's
elevated pulmonary vascular resistance. This study was performed to determine:
(1) the acute effects of brain death on the RV function; and (2) the adaptation
potential of the RV to a progressive increase in RV afterload. METHODS: In 13
anesthetized, open-chest dogs (eight with brain death vs. five control with sham
operation), brain death was induced by inflation of a subdural balloon catheter.
Heart rate, RV systolic and end-diastolic pressure (RVSP, RVEDP), pulmonary
arterial pressure (PAP), and cardiac output (CO), and pressure-length loops
(sonomicrometry) were recorded. Afterload increase was induced 2 h after brain
death induction by constriction of the pulmonary artery with an increase in RVP
from 25 to 50 mmHg in 5 mmHg steps. RESULTS: Cushing phenomenon occurred within a
few minutes after brain death induction, with a significant increase of HR (229
+/- 10 vs. 89 +/- 6 min(-1), P < 0.001), CO (3.2 +/- 0.2 vs. 1.7 +/- 0.1 l/min, P
< 0.001), PAP (30.4 +/- 2.5 vs. 15.5 +/- 1.3 mmHg, P < 0.01) RVSP (55 +/- 5 vs.
23 +/- 2 mmHg, P < 0.001) and RVEDP (7.4 +/- 0.9 vs. 3.3 +/- 0.6 mmHg, P <
0.001). All these values were also significantly (P < 0.01) higher than the time
corresponding values of the control group. The analysis of the pressure-length
loops showed a hypercontractile state. Within 15-60 min, all parameters turned to
baseline and remained stable for up to 2 h. When afterload was increased
progressively, RVEDP increased markedly in the brain death and slightly in the
control group (9.4 +/- 0.7 vs. 4.2 +/- 1.1 mmHg, P < 0.01, at RVSP = 50 mmHg). On
the other hand, the increase of peak positive dP/dt was significantly higher in
the control group (430 +/- 37 vs. 644 +/- 55 mmHg/s, P < 0.01, at RVP = 50 mmHg).
However, global RV pump function characterized by CO and stroke work was similar
in both groups. While regional RV contractility remained unchanged in the brain
death group in terms of pressure-length relationships, RV contractility
significantly increased in the control group. CONCLUSION: (1) Brain death per se
does not result in an acute impairment of RV function. (2) While control animals
adapt to an increased afterload by the homeometric, as well as the heterometric
regulation, after brain death, an increase in RV preload follows elevations in RV
afterload by the Frank-Starling mechanism subserving the increased stroke work
required to ensure unchanged pump function.
PMID- 9641346
TI - Gene transfer into rat heart-derived endothelial cells.
AB - OBJECTIVE: Progressive graft arteriosclerosis is responsible for the majority of
late deaths in cardiac transplant recipients. Despite many investigations, the
pathogenesis of this disease remains undetermined and its control inadequate. A
somatic gene transfer during the cold ischemic time and thus before
transplantation might be a new therapeutic tool. This approach allows a long
incubation time of the DNA and a safe transfer with liposomes and transferrin
with less adverse effects for the organ recipient. METHODS: The target cells
(microvascular endothelial cells (MVECs)) for this gene transfer were isolated
from rat hearts by perfusion with collagenase via an aortic cannulae. The cells
were purified by changing the medium 30 min after subcultivation in order to
remove fibroblasts and smooth muscle cells. The endothelial cells (ECs) were
identified by typical morphology and the uptake of Dil-Ac-LDL. The gene transfer
was carried out with a beta-galactosidase reporter plasmid (pCMVbeta), cationic
liposomes (Lipofectin), and transferrin. Different transfection solutions were
prepared with or without serum, and with different plasmid-liposome ratios and
transferrin concentrations. The transfer rate was monitored with a
semiquantitative orthonitrophenyl-beta/-D-galactoside (ONPG) assay and
histologically by X-Gal staining. The cytotoxicity of this procedure was
determined with a colorimetric ELISA with Alamar blue. The cardioplegic property
of the transfection solution was tested in a Langendorff perfusion system
monitoring the coronary blood flow over time after a cold ischemic time of 4 h.
RESULTS: The maximal gene expression could be detected after transfection with 4
microl Lipofectin, 2 microg pCMVbeta, and 16 microg transferrin/200 microl
transfection solution. Under these conditions 60% of the cells showed a blue
staining with X-Gal. Only 20% of the cells died during transfection. The lowest
cytotoxicity during cold ischemic time for ECs was assessed with normal cell
culture medium and the Buckberg solution. The best coronary flow rates after 4 h
cold ischemia of the heart were measured for cardioplegia with St. Thomas and
Buckberg solutions. In summary, the best transfection solution with a good
cardioplegic property was the Buckberg solution. CONCLUSIONS: Finally, the
results of this study show that an effective DNA delivery with a low toxicity
into ECs is possible with a combination of liposomes and transferrin. This method
might be useful for a safe and effective gene transfer into solid organs during
the cold ischemic time and thus a therapeutic tool for chronic rejection.
PMID- 9641347
TI - Influence of heat stress on myocardial metabolism and functional recovery after
cardioplegic arrest: a 31P N.M.R study.
AB - OBJECTIVE: Heat stress and induction of heat shock proteins confer protection
against myocardial ischemia-reperfusion injury; however the precise mechanisms of
this effect remain unknown. We investigated the influence of heat stress on
metabolic and functional recovery after cardioplegic arrest, in a protocol
mimicking clinical donor heart preservation. METHODS: Langendorff perfused rat
hearts in control group (C, n = 6) and heat stressed (24 h prior to experiment)
group (HS, n = 6) were subjected to 4 h of ischemia at 4 degrees C following
cardioplegic arrest (St. Thomas' No. 1). 31P nuclear magnetic resonance
spectroscopy was used to follow changes in ATP, phosphocreatine and inorganic
phosphate concentrations during the pre-ischemic, ischemic and reperfusion
periods. Myocardial adenine nucleotide levels in hearts at the end of experiments
and purine catabolite release in coronary effluent during reperfusion, were
evaluated using high performance liquid chromatography. Mechanical function in
the pre-ischemic and reperfusion periods was evaluated using an intraventricular
balloon. Western immunoblotting was used to quantitate HSP70 expression. RESULTS:
Although baseline concentrations of ATP and phosphocreatine were similar in C and
HS groups, the rate of high-energy phosphate depletion was attenuated during the
early phase of ischemia in HS groups. On reperfusion, recovery of ATP was 10-20%
greater in HS versus C groups; phosphocreatine levels also recovered better in
the HS group, transiently reaching levels 40% higher in HS versus C groups. The
concentrations of adenine nucleotides in hearts were significantly higher in the
HS versus C groups. These changes were associated with an attenuation of total
purine catabolite release in the coronary effluent in HS versus C groups. A
significant improvement in relative recovery of developed pressure was shown in
HS versus C groups in the post-ischemic periods. CONCLUSIONS: Heat stress causes
beneficial changes in high-energy phosphate metabolism in the rat heart subjected
to cardioplegic arrest and ischemia. Improved mechanical recovery in HS versus C
groups was associated with a decreased rate of high-energy phosphate depletion
and increased recovery of ATP and phosphocreatine levels during reperfusion.
Changes in energy metabolism may play a role in the mechanism of cardioprotection
by heat stress during prolonged hypothermic cardiac arrest. rights reserved.
PMID- 9641348
TI - Influence of ageing on functional recovery and guanine nucleotide levels of the
heart following cold cardioplegic arrest.
AB - OBJECTIVE: The effect of age on metabolism and mechanical recovery of the heart
after cardioplegic arrest is important, but remains a relatively unexplored
subject. In this study, functional recovery and nucleotide levels were compared
in the heart at different ages subjected to prolonged hypothermic cardioplegic
arrest. METHODS: Three different age groups of rats: 1 (A); 4 (B); and 16 months
(C) were perfused in working mode and subjected to cardioplegic arrest (St.
Thomas' No. 1) and ischemia for 4 h at 4 degrees C, followed by reperfusion for
35 min. Cardiac function (cardiac output and aortic pressure) was recorded before
and after ischemia. Another series of hearts in all three age groups underwent 5
min of normoxic perfusion to obtain pre-ischemic baseline metabolite
concentrations. Hearts were freeze-clamped at the end of each experiment and used
for determination of nucleotide and creatine metabolites by HPLC. RESULTS: The
post-ischemic recovery (% of the pre-ischemic value) of the cardiac power was
48.9 +/- 7.8% for group A, which was significantly higher than the functional
recovery of group B (24.1 +/- 3.5%) or C (21.4 +/- 4.7%, P < 0.05, respectively).
There was no difference in ATP or the total adenine nucleotide or creatine
metabolite concentrations between the three age groups. In contrast, both GTP and
the total guanine nucleotide concentration was highest in A (P < 0.05). Total
guanylate pool was 1.52 +/- 0.10 1 micromol/g dry wt. in A, as compared to B
(1.05 +/- 0.04) or C (1.12 +/- 0.04). NAD was significantly higher in B (4.1 +/-
0.1. P < 0.05), when compared to A (3.6 +/- 0.1) and C (3.8 +/- 0.1). CONCLUSION:
Best post-ischemic functional recovery after cardioplegic arrest was observed in
the 1-month-old hearts (A) and was associated with highest guanine nucleotide
concentration; preservation of guanine nucleotide pool in the youngest hearts may
be an important mechanism for improved cardioprotection due to the important role
of GTP in signalling pathways.
PMID- 9641349
TI - Presentation of a pseudoaneurysm as a supravalvular aortic stenosis 20 years
after aortic root reconstruction.
AB - A 36-year-old patient was referred because of fatigue and decreased exercise
tolerance 20 years after separate aortic valve replacement and aortic root
reconstruction. The presence of a loud systolic ejection murmur and persistent
left ventricular hypertrophy led to the diagnosis of severe supravalvular aortic
flow obstruction by indirect compression of a large pseudoaneurysm.
PMID- 9641350
TI - Composite graft replacement for treatment of ascending aortic aneurysms using
original Bentall-DeBono procedure or its open button modification.
PMID- 9641351
TI - VATS resection of oesophageal leiomyomas.
PMID- 9641352
TI - Determinants of Clara cell protein (CC16) concentration in serum: a reassessment
with two different immunoassays.
AB - Clara cell protein (CC16) is a 16 kiloDalton protein secreted by Clara cells in
the lining fluid of bronchiolar and bronchial epithelium. Recently, Nomori et
al., using a nephelometric latex immunoassay, reported a strong correlation
between serum CC16 (sCC16) and serum lipids as well as the body mass index (BMI)
[Nomori H, Horio H, Takagi M Kobayashi Y, Hirabayashi Y. Clara cell protein
correlation with hyperlipidemia. Chest 1996;110:680-4]. The same authors found
higher values of sCC16 in males compared to females and did not detect any
significant influence of tobacco smoking. Since these results are in disagreement
with previous observations showing consistently a decrease of sCC16 in smokers
and no influence of sex, we have reassessed in healthy subjects the determinants
of sCC16 using two different assays: a particle counting-based latex immunoassay
(LIA) using polyclonal antibodies and a fluorescence enzyme immunoassay (FEIA)
using monoclonal antibodies. sCC16 was determined in a group of 52 female and 44
male healthy subjects (age 18 to 66 years), including 35 smokers and 61
nonsmokers. sCC16 measured by LIA and FEIA were well correlated (r = 0.92, n =
96, P < 0.0001) with values (geometric mean and range) of 13.3 (5.2-34.5) and
14.7 (4.1-53.1) microg/l, respectively. The determinants of sCC16 measured by
both techniques were traced by stepwise regression analysis using as independent
variables age, sex, smoking status, BMI or serum lipids (total cholesterol and
triglycerides) and the glomerular filtration rate (GFR) estimated on the basis of
serum creatinine or beta2-microglobulin. Only two significant determinants
emerged: tobacco smoking which correlated negatively and the GFR which correlated
positively with sCC16. No influence of serum lipids, BMI, age and sex on sCC16
was detected. We think that an analytical interference with serum lipids explains
the results by Nomori et al. which are not confirmed here by two independent
techniques and are inconsistent with the current understanding of the
physiopathology of the Clara cell and its main secretory product, CC16.
PMID- 9641353
TI - Analysis of human primary bone cells by fluorescence activated cell scanning:
methodological problems and preliminary results.
AB - We describe the development of flowcytometrical methods to analyse human primary
osteoblast-like cultures obtained from trabecular bone explants in comparison to
the human osteosarcoma cell line HOS 58. Two antigens typical of osteoblasts were
studied: bone alkaline phosphatase and collagen/procollagen I; the non-specific
attachment protein fibronectin served as control. The morphology of all different
antigens is shown by immunocytochemistry before flowcytometrical analysis. The
establishment of flowcytometry is described in detail. While all antigens tested
were nearly 100% positive in the HOS 58 cells in immunocytochemistry and
flowcytometry, in primary osteoblast-like cells results varied widely between
both methods. Cell permeabilisation before flowcytometry improved the homogeneity
of results, probably by increasing the accessibility of the specific antibody to
intracellular compartments. Though up to 80% of cells were lost during
preparation the ratio of positive versus negative cells in specific experiment
was not dependent on the cell recovery. Therefore, the cells finally analysed
seemed to be representative of the total population.
PMID- 9641354
TI - Clinical chemistry variables in normal elderly and healthy ambulatory
populations: comparison with reference values.
AB - Laboratory values of the most commonly assayed clinical chemistry variables were
determined in selected elderly and healthy ambulatory populations. The upper and
lower limits (2.5 and 97.5 fractiles) were compared with the adult reference
values in use in university hospitals of Switzerland. The results suggest that
conventional adult reference values can be used for most variables in the elderly
and that these values are also useful in an ambulatory population.
PMID- 9641355
TI - Amylase measurement with 2-chloro-4-nitrophenyl maltotrioside as substrate.
AB - The use of 2-chloro-4-nitrophenyl maltotrioside (CNP-G3) as substrate to measure
amylase (EC 3.2.1.1) activity in serum directly without the use of auxiliary
enzymes was evaluated at two centres. The method was precise (within-run C.V. <
2% and between-run C.V. < 3%), there was no lag phase, background absorbance was
low and there were minimal effects of pH changes. When compared with a method
which uses 4,6-ethylidene (G7)-p-nitrophenyl (G1)-alpha-D-maltoheptaoside (EPS
G7) as substrate, the CNP-G3 method had greater sensitivity and longer reagent
stability (21 days compared with 2 days at 4 degrees C). The activity measured
with the CNP-G3 method correlated well with methods using either EPS-G7 and
maltotetraose as substrates.
PMID- 9641356
TI - Lack of correlation of free deoxypyridinoline excretion with Taq1 restriction
length polymorphisms in the vitamin D receptor gene in males.
AB - An association between allelic variants in the vitamin D receptor gene and bone
mineral density has been previously described. A bimodal variation in the rate of
bone resorption (as measured by urinary deoxypyridinoline excretion rate) has
also been reported. We have recruited male volunteers, to minimise variation
associated with ovarian function, to investigate a possible connection between
these observations. Allelic variants in the vitamin D receptor gene were
identified as Taq1 restriction fragment length polymorphisms. The ratio of
variants TT:Tt:tt occurred with a frequency of 34%:47%:17%. Excretion rates of
urinary free deoxypyridinoline, measured by immunoassay, were compared in age
matched males from each genetic group. There were no significant differences
based on the paired Student's t-test. Excretion rates declined with age (P =
0.04) and the best fit model fits the same regression line to each group. Genetic
variation in the vitamin D receptor is not linked with differences in bone
resorption rates.
PMID- 9641357
TI - Carbohydrate deficient transferrin in the assessment of alcohol misuse: absolute
or relative measurements? A comparison of two methods with regard to total
transferrin concentration.
AB - Carbohydrate deficient transferrin (CDT) is now accepted as a potentially useful
marker for the detection of alcohol misuse. It is not clear whether absolute
values or values expressed relative to the total transferrin concentration
provide the same diagnostic efficiency. CDT was measured in 35 patients with
alcohol related liver disease, 35 subjects abusing alcohol without evidence of
liver disease and 35 patients with chronic viral hepatitis using two commercial
methods (CDTect and %CDT). To compare the methods, results were normalised by
dividing the actual result by the upper limit of the reference range. Subtracting
normalised %CDT results from the normalised CDTect results demonstrated a linear
relationship between CDTect and total transferrin. This linear relationship could
be abolished by calculating the CDTect/total transferrin ratio. The sensitivity
of the methods was similar with CDTect (43 and 57%) being slightly superior to
%CDT (40 and 46%). Specificity was similar (78%) for both methods. Calculation of
the CDTect/total transferrin ratio improved the sensitivity and specificity
slightly. The linear relationship between CDTect and total transferrin may
produce misleading results in populations with a high prevalence of abnormal
total transferrin concentrations and could cause difficulties in method
comparisons unless taken into account.
PMID- 9641358
TI - Troponin I, troponin T, CKMB-activity and CKMB-mass as markers for the detection
of myocardial contusion in patients who experienced blunt trauma.
AB - Myocardial contusion is an infrequent, but sometimes serious complication in
patients who experienced deceleration (blunt) trauma. We investigated the
assessment of the new cardiac markers troponin I (cTnI) and troponin T (cTnT) in
relation to the conventional CKMB-activity, the CKMB-activity/CK-total ratio,
CKMB-mass and the CKMB-mass/CK-total ratio for the detection of myocardial
contusion in 89 patients with blunt trauma (38 patients with thoracic injuries
and 51 patients without thoracic injuries). All parameters were analysed at
admission (t1) and 24 h after admission (t2). For the patients with thoracic
injuries, at t1 cTnI was elevated in three, and cTnT in four patients; at t2 both
cTnI and cTnT were elevated in nine patients. At t1, eighteen to thirty patients
had increased levels of the conventional parameters; at t2 this was true for six
to thirty-five patients. For the patients without thoracic injuries all cTnI and
cTnT levels were within the reference ranges at t1. At t2 one patient, who
experienced an acute myocardial infarction, had elevated cTnI and cTnT levels. At
t1, five to thirty-five patients had increased levels of the conventional
parameters; at t2 this was true for four to forty-two patients. From this study
we conclude that the conventional parameters are not useful for the detection of
myocardial contusion in patients experiencing blunt trauma. The parameters cTnI
and cTnT are equally accurate and more reliable for the selection of patients who
require intensive cardiac monitoring. If at admission the cTnI or the cTnT levels
are within the reference ranges, a second analysis after admission is necessary
to reach a reliable conclusion concerning myocardial contusion as a result of
trauma on basis of the troponin levels.
PMID- 9641359
TI - Evaluation of the new automated ELISA Vidas Lp(a) assay. Comparison with an
immunonephelemetric method.
AB - Lipoprotein (a) [Lp(a)] is a lipoprotein which has a plasma concentration that is
highly correlated with cardiovascular disease. In this study, the new Lp(a) assay
for the Vitek Immuno-Diagnostic Assay System (VIDAS) developed by bioMerieux was
evaluated. This method uses an enzyme linked fluorescent immunoassay (ELFIA)
technique. Within-run and between-run reproducibility of the Vidass Lp(a) assay
are characterized by coefficients of variation (CV) of 3 to 5.9% and 3.9 to 5.9%,
respectively. Using analysis of variance, no statistical difference was shown
between ELFIA and immunonephelometric assay (INA). When comparing results of the
Vidas Lp(a) test with the INA, a highly significant correlation of r = 0.9708 and
regression line equation y = 0.963x-0.037 was found. Interference of lipemia was
studied: no influence was observed up to 12.3 mmol l(-1) triglycerides. No
interference of haemoglobin was noted for Lp(a) > 0.20 g l(-1).
Hyperbilirubinemia ( > 120 micromol l(-1)) led to results being underestimated
for concentrations of Lp(a) which were < 0.20 g l(-1). No pre-analytical
interference of citrate was measured but pre-analytical interference of EDTA was
found. In conclusion, this new fully automated immunofluorimetric Lp(a) assay
enables to the rapid, accurate and reliable determination of Lp(a) in blood
samples.
PMID- 9641360
TI - Autoantibodies to gangliosides in sera of atherosclerotic patients.
AB - Using ELISA we studied the levels and clinical correlation of serum antibodies
against gangliosides and 5-hydroxytryptamine (5-HT) in patients with
atherosclerosis and clinical manifestations of cardiovascular disease. A range of
70-80% of the patients showed higher titers of anti-GM3(L) and anti-5HT as
compared to normal serum. The anti-GM3(L) antibodies appeared to be directed
mainly against GM3 present in platelets and were much less reactive against GM3
isolated from the aorta. We concluded that the antigens responsible for the
elevated anti-GM3(L) and anti 5-HT levels in atherosclerotic sera are released by
vessel-wall activated platelets. These results provide further evidence of on
going autoimmune processes in atherosclerosis. The content of total sialic (TS)
and lipid-bound sialic acid (LBS) was measured in sera of patients with IHD and
of similar numbers of healthy donors. In the patient groups the average TS and
LBS concentration was about 25% higher than in the control group. These changes
appeared to be associated with higher degrees of protein sialylation and larger
amounts of LDL in the patient sera than in those of healthy controls.
PMID- 9641361
TI - Thrombolytic therapy does not change the release ratios of enzymatic and non
enzymatic myocardial marker proteins.
AB - Measurements of cardiac marker proteins in plasma from patients with acute
myocardial infarction (AMI) have become important in the evaluation of
recanalization therapy. The validity of this approach has however been
questioned, because it was claimed that coronary reperfusion may increase the
recovery in plasma of cardiac enzymes, such as creatine kinase (CK). In the
present study, possible effects of thrombolytic therapy on the release of
enzymatic and nonenzymatic marker proteins were investigated. Activities of CK
and lactate dehydrogenase (LDH), and concentrations of myoglobin (Mb) and fatty
acid-binding protein (FABP) were determined in serial plasma samples obtained
from 50 patients with confirmed AMI, of whom 36 received thrombolytic therapy,
and 14 did not. Treatment delay was 2.8+/-1.6 (mean+/-SD) h, and hospital delay
in untreated patients was 2.7+/-1.8 h. Average infarct size, expressed in gram
equivalents of heart muscle per litre of plasma (g-eq/l), varied between 5.5 and
7.2 g-eq/l for the four marker proteins in patients treated with thrombolytic
therapy, and between 4.6 and 6.4 g-eq/l in untreated patients, with a tendency to
larger infarct sizes for Mb and FABP than for CK and LDH. Thrombolytic therapy,
although significantly accelerating protein release rates, did not influence the
release ratios. These results indicate that thrombolytic therapy has no
significant effects on the recovery of cardiac marker proteins in plasma.
PMID- 9641362
TI - Reference range of some enzymes and proteins in untimed overnight urine and their
stability after freezing.
PMID- 9641363
TI - Short Synacthen test: standard versus low dose in the evaluation of patients with
pituitary diseases.
PMID- 9641364
TI - Guidelines for the correct conduct of clinical research in surgery.
AB - Clinical research may be either epidemiological or experimental. Epidemiological
(observational) research includes cross-sectional, case-control, and cohort
studies and draws attention to associations, which may or may not denote cause
and effect. Experimental research may be explanatory, the purpose of which is to
advance our knowledge of physiological or pathological events; or it may be
pragmatic, the purpose of which is to influence our treatment of patients. All
these types of clinical research have their own rules, but underlying the
detailed rules are the universal ones of telling the truth and doing no harm.
PMID- 9641365
TI - Hyperbaric oxygen in the treatment of Fournier's gangrene.
AB - OBJECTIVE: To investigate the efficacy of operation, antibiotic treatment,
hyperbaric oxygen, and surgical intensive care in the management of Fournier's
gangrene. DESIGN: Retrospective study. SETTING: University hospital, Finland.
SUBJECTS: 33 patients, most of them referred from other hospitals. INTERVENTION:
Debridement, broad spectrum antibiotics, and hyperbaric oxygen (HBO) treatment at
2.5 atmospheres absolute pressure. Excision of necrotic tissue and incisions in
the affected areas. Urinary and faecal diversions when necessary. MAIN OUTCOME
MEASURES: Morbidity and mortality. RESULTS: Only three patients died (9%).
Hyperbaric oxygen reduced systemic toxicity, prevented extension of the
necrotising infection, and increased demarcation, thereby improving the overall
outcome. CONCLUSION: To reduce mortality and morbidity, effective treatment of
Fournier's gangrene should be started promptly. Debridement and antibiotics
combined with surgical intensive care must be started as soon as possible.
Hyperbaric oxygen is both life and tissue saving. It is an important adjunct that
prevents extension of necrosis and reduces systemic toxicity.
PMID- 9641366
TI - Rapid increase in volume of the remnant after hemithyroidectomy does not
correlate with serum concentration of thyroid stimulating hormone.
AB - OBJECTIVE: To study the effect of postoperative thyroxine on the volume of the
thyroid remnant after lobectomy for benign nontoxic goitre. DESIGN: Prospective,
randomised study. SETTING: University hospital, Sweden. SUBJECTS: 50 consecutive
patients who underwent lobectomy for benign non-toxic goitre. INTERVENTIONS:
Patients were randomised postoperatively to take thyroxine 0.1 mg or placebo
daily. MAIN OUTCOME MEASURES: The median volume of the remaining thyroid lobe
measured by ultrasound. Serum concentrations of thyroxine, triiodothyronine (T3)
and thyroid stimulating hormone (TSH) were measured preoperatively and 1, 3, 6,
12 months postoperatively. RESULTS: The median volume of the remaining lobe had
increased significantly compared with preoperatively by 1 month postoperatively
by 30% in the thyroxine group and 25% in the placebo group (p < 0.01). The
difference between the groups was not significant. After the first month the
volume did not change significantly. In the thyroxine group, the TSH
concentration was unchanged and the thyroxine concentration increased
significantly throughout the study. In the placebo group there was a significant
increase in TSH concentration and a significant decrease in that of thyroxine at
all follow-up examinations. CONCLUSIONS: There is a significant increase in the
volume of the remaining thyroid 1 month after lobectomy that persisted throughout
the first year. Thyroxine given in a dose that kept the serum TSH concentration
at the same level as preoperatively did not seem to influence volume changes;
consequently we consider that these are caused by factors other than TSH.
PMID- 9641367
TI - An "all comers" policy for ruptured abdominal aortic aneurysms: how can results
be improved?
AB - OBJECTIVE: To review our experience of a non-selective policy for the treatment
of ruptured abdominal aortic aneurysm to see if the policy was justified, and to
identify any preoperative risk factors that adversely influenced outcome. DESIGN:
Retrospective study. SETTING: Teaching hospital, Republic of Ireland. SUBJECTS:
258 patients admitted with abdominal aortic aneurysms between January 1982 and
December 1993. INTERVENTIONS: Definitive surgical treatment. MAIN OUTCOME
MEASURES: Morbidity, mortality, and risk factors. RESULTS: In-hospital mortality
for all patients was 43% (110/258). Overall, women did worse than men (28/44,
64%, died, compared with 96/214, 45%, p=0.03). The mortality among patients over
the age of 80 (23/45, 51%) was not significantly different from that among
younger patients (97/202, 48%). Blood pressure, platelet count, and haemoglobin
concentration were all significantly lower preoperatively among those who died (p
< 0.05). CONCLUSIONS: Age alone cannot be used to justify witholding definitive
surgical treatment. Treatment should be aimed towards reversing haematological
and haemodynamic abnormalities preoperatively to try to improve outcome.
PMID- 9641368
TI - Cardiff repair of incisional hernia: a university hospital experience.
AB - OBJECTIVE: To analyse our results of the "Cardiff' (far and near) repair in
incisional hernias. DESIGN: Prospective study. SETTING: University hospital,
Varanasi, India. SUBJECTS: 50 patients who presented with incisional hernias
between January 1990 and December 1994. INTERVENTION: Interrupted far-and-near
sutures inserted after excision of the sac. The contents were pushed into the
abdomen and the peritoneum sutured with non-absorbable polypropylene (prolene).
MAIN OUTCOME MEASURES: Early and late morbidity. Six patients developed
postoperative complications (wound infection, n=3; flap necrosis, n=2; and wound
sinus, n=1). No patient has been lost to follow up and there have been no signs
of recurrence after a mean follow up of 52 months. CONCLUSION: The meticulous
application of this simple surgical technique has low morbidity and is cost
effective. We recommend it for small and medium size defects.
PMID- 9641369
TI - Morgagni's hernia in infants and children.
AB - OBJECTIVE: To report my experience of Morgagni's hernia in 4 infants and 1 child.
DESIGN: Retrospective study. SETTING: Teaching hospital, Saudi Arabia. SUBJECTS:
4 infants and 1 child with Morgagni's hernias, one of which was recurrent.
INTERVENTIONS: Repair through an abdominal incision. MAIN OUTCOME MEASURES:
Presentation, morbidity, and recurrence. RESULTS: 4 of the 5 cases presented with
respiratory distress or pulmonary infection, or both; 1 presented with failure to
thrive as well. 3 patients had associated anomalies (hypertrophic pyloric
stenosis, malrotation of the gut, and left inguinal hernia; Down syndrome; and
multiple Mongolian spots and umbilical hernia). The hernia was recognised on
chest radiograph in all cases, and confirmed by barium studies in 3. All the
hernias were repaired through an abdominal incision. There were no deaths and no
early complications, but late complications included a recurrence and incisional
hernia in 1 patient and midgut volvulus caused by associated anomalies in
another. CONCLUSION: Outcome is usually influenced by associated anomalies and
the seriousness of the effects of the hernia. Timely diagnosis and repair can
improve outcome.
PMID- 9641370
TI - Long term follow up of patients who underwent jejunoileal bypass for morbid
obesity.
AB - OBJECTIVE: To describe our long term results after jejunoileal (JI) bypass for
morbid obesity. DESIGN: Retrospective study. SETTING: Teaching hospital, Denmark
SUBJECTS: All 57 patients who underwent JI bypass for morbid obesity between
January 1973 and December 1988. INTERVENTIONS: Type A and type B JI bypass. MAIN
OUTCOME MEASURES: Weight loss, operative morbidity and mortality, and subjective
evaluation of the results. RESULTS: Mean duration of follow up was 15.9 years
(range 8-22). There were no operative or early postoperative deaths, but there
were 7 late deaths (12%). 5 patients developed postoperative complications (9%),
and 11 patients (19%) required reoperation for side effects or complications. The
mean body mass index (BMI, kg/m2) was reduced from 47.5 (range 40-60) to 32
(range 22-49) during the follow up period which corresponded to a weight loss of
about 42 kg. Of the 39 patients who still had a JI bypass in 1994, nearly two
thirds said that they were satisfied with the operation, though they nearly all
had some side effects such as diarrhoea or intermittent abdominal pain.
CONCLUSION: As complications of JI bypass can develop at any time, we suggest
that all patients who have had the operation should be regularly followed up at
special clinics so that complications can be diagnosed and treated as soon as
possible.
PMID- 9641371
TI - A survey of surgical treatment of gallstone disease and the diffusion of
laparoscopic surgery in Sweden 1992-93.
AB - OBJECTIVE: To study the diffusion of laparoscopic biliary surgery in Sweden, 1992
93. DESIGN: A prospective survey of all biliary surgery for gallstone disease
recorded for 8 weeks in 1992 and the same period in 1993. SETTING: All surgical
departments in Sweden. SUBJECTS: A consecutive series of 1938 patients in 1992
and 1748 patients in 1993. MAIN OUTCOME MEASURES: The changing indications,
diffusion, morbidity, mortality, postoperative and hospital stay after
laparoscopic cholecystectomy (LC) in Sweden in 1992 compared with 1993. RESULTS:
Despite the spread of LC, the indications did not change between 1992 and 1993
(p=0.31). The total number of cholecystectomies decreased from 1938 in 1992 to
1748 in 1993. The overall percentage of laparoscopic cholecystectomies (LCs)
increased from 74.7% to 81.2% (p <0.001) between 1992 and 1993. Postoperative
morbidity and mortality after LC did not differ between 1992 and 1993, but the
total morbidity was 9.0% in 1992 and 7.0% in 1993 (p=0.02). Mortality for all
cholecystectomies did not change over the periods, being 0.6% in 1992 and 0.2% in
1993 (p=0.07). The numbers of LCs done in any hospital were divided in two
groups, 20 or fewer and 21-80. In the smaller group, the postoperative morbidity
was 7.1% and in the larger group it was 7.0%, (p=0.9). The postoperative
mortality was 0.1% in both groups. The postoperative and total hospital stays of
all cholecystectomies decreased from 3.4 days in 1992 to 2.9 days in 1993
(p=0.001) and from 5.0 in 1992 to 4.4 days in 1993 (p < 0.001), respectively. The
postoperative and total hospital stays of LCs decreased from 2.0 in 1992 to 1.8
days in 1993 (p=0.009) and from 3.3 in 1992 to 2.9 days in 1993 (p=0.007),
respectively. CONCLUSION: Despite the introduction and diffusion of the new
technology, LC, the indications for surgery did not change and the number of
cholecystectomies did not increase from 1992 to 1993. The morbidity and mortality
of LC and the mortality of all cholecystectomies were unchanged between 1992 and
1993, but the morbidity for all cholecystectomies decreased. The number of LC or
all cholecystectomies done in any particular hospital were not related to
morbidity or to mortality.
PMID- 9641372
TI - An experimental study on effects of monopolar diathermy on the bile ducts.
AB - OBJECTIVE: To study the effects of monopolar diathermy on the bile ducts in pigs.
DESIGN: Experimental study. SETTING: University hospital, Norway. MATERIAL: 18
pigs. INTERVENTIONS: Laparotomy, application of diathermy at standard sites along
the cystic duct, the bile ducts, and a cystic duct containing a metal clip, 3 to
12 times of 5 seconds' duration at each site. Temperature was subsequently
recorded at standard measurement points on the bile ducts. Twelve pigs were
killed after three weeks for assessment of the bile ducts at necropsy. MAIN
OUTCOME MEASUREMENTS: Increase in temperature in the bile duct walls and late
changes in the bile ducts. RESULTS: Temperature increased by 4-6 degrees C during
6 of 330 diathermy applications along the cystic duct, by 4-18 degrees C in 8 of
126 applications along the common bile duct, and by 4-11 degrees C at the clip in
9 of 54 applications. There were no macroscopic or microscopic changes in the
bile ducts. CONCLUSION: Monopolar diathermy induced unexpected distant increases
in the temperature of the bile duct walls and at a clip on the cystic duct
probably because diathermy current energy was distributed along channels of high
current conductivity.
PMID- 9641373
TI - Full thickness resection of radiation-induced ulcers of the chest wall:
reconstruction with absorbable implants, pedicled omentoplasty, and split skin
graft.
PMID- 9641374
TI - Pancreatoblastoma in an adolescent girl: case report and review of 26 Japanese
cases.
PMID- 9641375
TI - Spontaneous rupture of the oesophagus in an adolescent with type IV Ehlers-Danlos
syndrome. Ehlers-Danlos and spontaneous oesophageal rupture.
PMID- 9641376
TI - Thoracoscopic upper thoracic sympathectomy for primary palmar hyperhidrosis--the
combined paediatric, adolescents and adult experience.
AB - OBJECTIVE: To present our experience, over the past 4 years, of thoracoscopic
upper thoracic sympathectomy in patients with primary palmar hyperhidrosis.
DESIGN: Retrospective study. SETTING: University hospital, Israel. SUBJECTS: 402
thoracoscopic upper thoracic sympathectomies in 223 patients over a period of 4
years. INTERVENTIONS: Thoracoscopic ablation of ganglia and severing of the
sympathetic chain at the level of T2 and T3. 142 patients underwent bilateral
simultaneous sympathectomy, 37 had bilateral non-simultaneous sympathectomy and
44 had unilateral sympathectomy. RESULTS: 220 patients (98.7%) had an uneventful
postoperative course and were discharged the following day. Three patients with
residual pneumothorax required intercostal drainage and were discharged on the
third postoperative day. 219 patients (98.2%) were completely satisfied, having
immediate and permanent relief of palmar sweating. Four patients were
dissatisfied. CONCLUSION: The thoracoscopic approach to the upper thoracic
sympathectomy is at present the procedure of choice. Early operation for severe
palmar hyperhidrosis is indicated to save a child many years of frustration and
discomfort.
PMID- 9641377
TI - Improvements in video-endoscopic sympathicotomy for the treatment of palmar,
axillary, facial, and palmar-plantar hyperhidrosis.
AB - Video-endoscopic sympathicotomy for the treatment of palmar, axillary, facial and
palmar-plantar hyperhidrosis was modified as to the type of surgical access and
the level of incision in the sympathetic chain and communicating rami, depending
on the clinical indications. Under general anaesthesia, using a single lumen
endotracheal tube, the patient is put in lateral decubitus and pneumothorax is
induced. The patient is then placed in ventral decubitus, with the head elevated,
to make two punctures in the posterior axillary line, at the level of the 4th and
7th intercostal spaces, to introduce two ports of 5 and 10 mm in size,
respectively. The sympathetic chain and the communicating rami are viewed and
severed, according to the indications, at different levels to treat palmar,
axillary, facial and palmar-plantar hyperhidrosis and combinations of the above.
The operation is performed on both sides of the thorax during the same period of
anaesthesia. One hundred-forty patients (280 procedures) have been operated on
from 1993 to 1997 using this technique. All were operated on as outpatients. Our
results are: 100% of those with facial and palmar hyperhidrosis and 96% of those
with axillar hyperhidrosis were cured, and 94% with plantar hyperhidrosis were
relieved from 50 to 100%, with the follow-up of between one and 47 months.
PMID- 9641378
TI - Thoracoscopic T2-sympathetic block by clipping--a better and reversible operation
for treatment of hyperhidrosis palmaris: experience with 326 cases.
AB - Although thoracoscopic sympathectomy or sympathicotomy is the best treatment for
hyperhidrosis palmaris, a new approach of clipping only without transection of T2
sympathetic trunk is just as effective. Aside from the guaranteed cure of
hyperhidrosis, this new method has fewer complications and has the advantage of
recovery of the sympathetic tone in the hands if the procedure is reversed by the
removal of the clips. Between March 18 and September 30 of 1996, 326 patients
(190 female and 136 male with a mean age of 20.5 years) underwent thoracoscopic
T2-sympathetic block by clipping to treat hyperhidrosis. Good results and few
complications were noted during follow up six months to one year postoperatively.
Five of the 326 patients, all female, had the operation reversed because of
intolerable compensatory sweating. Three recovered from the compensatory sweating
within two months and had less palmar sweating than before their sympathetic
block; the fourth achieved relief of compensatory sweating after nine months, and
the fifth reported no improvement.
PMID- 9641379
TI - Secondary sympathetic chain reconstruction after endoscopic thoracic
sympathicotomy.
AB - Thoracoscopic sympathicotomy by electrocautery is an irreversible procedure. Thus
the indications must be meticulously considered before the final decision to
operate is taken by both the surgeon and the patient. All possible side effects
should be dealt with and written informed consent required. A case of an open
nerve reconstruction of the divided sympathetic chains is presented. One year
after the reconstruction the patient reported subjective relief of the
compensatory oversweating and restoration of sweating in the face and the armpit.
Reversible methods like clipping the sympathetic chain should be considered
whenever feasible instead of the irreversible electrocoagulation of the
sympathetic chain.
PMID- 9641380
TI - Thoracoscopic sympathectomy: the U.S. experience.
AB - OBJECTIVE: 48 patients underwent TSSYM. Charts of patients undergoing
thoracoscopy were reviewed to assess the safety and efficacy of thoracoscopic
sympathectomy (TSSYM). DESIGN: A retrospective review was undertaken at four
United States medical centers. RESULTS: TSSYM was performed for reflex
sympathetic dystrophy in 27 patients, hyperhydrosis palmaris in 15 patients, and
Raynaud's upper extremity ischemia and splanchnic pain in 2 patients each.
Anesthesia with one lung ventilation was used. 2.9 ports were used per patient
and 0.8 chest tubes were placed per patient. All patients underwent resection of
the sympathetic chain, usually with a clip along the bottom of the resected
chain. Laser, electro-ablation and electroresection were not used by any of the
surgeons in his series. The mean length of hospital stay was 1.8 days.
CONCLUSIONS: TSSYM is a safe and effective technique for treatment of a variety
of thoracic disorders.
PMID- 9641381
TI - The Boras experience of endoscopic thoracic sympathicotomy for palmar, axillary,
facial hyperhidrosis and facial blushing.
AB - OBJECTIVE: To study the outcome of endoscopic thoracic sympaticotomy (ETS) for
palmar, axillary, facial hyperhidrosis and facial blushing. SUBJECTS: 1152
patients, 59% women and 41% men. INTERVENTION: ETS was performed by transection
of the sympathetic chain where it overlies the second and third rib. The nerve
was divided also over the fourth rib in patients with axillary hyperhidrosis.
Questionnaires were sent to all patients. MAIN OUTCOME MEASURES: The effect of
surgery was assessed by a 10 grad visual analogue scale (VAS) by the patients.
The results were divided into effect rate (the effect on the symptom) and overall
satisfaction rate, taking into account any side effects and complications apart
from the effect. RESULTS: The response rate was 90%. The mean follow up time,
effect rate and overall satisfaction rate were: 38 months for palmar
hyperhidrosis, 99.4% and 87%; 26 months for axillary hyperhidrosis, 94.5% and
68%; 31 months for facial hyperhidrosis, 97% and 76%; 8 months for facial
blushing, 96% and 85%. CONCLUSION: ETS is a very effective procedure in palmar,
axillary and facial hyperhidrosis and facial blushing. The overall satisfaction
rate is very good for palmar hyperhidrosis and facial blushing, not equally good
but acceptable for facial hyperhidrosis. The lower satisfaction rate in patients
with axillary hyperhidrosis makes this a questionable indication for ETS.
PMID- 9641382
TI - Treatment of social phobia by endoscopic thoracic sympathicotomy.
AB - OBJECTIVE: To analyse the severity of various symptoms and the developmental life
history in social phobia. To estimate the value of ETS in the treatment of
chronic social phobia. DESIGN: Prospective study. SETTING: Clinic for
Psychoneurology and Surgery in Tampere, Finland. SUBJECTS: Consecutive series of
patients (n = 51). INTERVENTIONS: Endoscopic thoracic sympathicotomy. MAIN
OUTCOME MEASURES: Qualitative ideographic inquiry. Questionnaire of the symptom
severity using visual analogue scale. RESULTS: The life history included mental
and physical abuse in 61%, paternal alcoholism in 26%. Four family subtypes were
named: quarrelsome, cruel, alcoholic, and perfectionist. The pathognomonic
symptoms of social phobia: hyperhidrosis, palpitation, blushing, tremor, and
anxiety, were all highly significantly (p < 0.001) alleviated by ETS. 88% of the
patients were satisfied with the result. There were no complications. CONCLUSION:
ETS seems a promising alternative to conservative therapy for social phobia.
PMID- 9641383
TI - Complications of endoscopic sympathectomy.
AB - Four cases are presented in which complications occurred during or after thoracic
endoscopic sympathectomy (TES). In one patient inappropriate TES resulted in
disabling hyperhidrosis. In one patient laceration of the subclavian artery
required major surgery. In two cases intraoperative cerebral damage occurred.
Training in TES is essential.
PMID- 9641384
TI - The haemodynamic effect of thoracoscopic cardiac sympathectomy.
AB - A patient with angina pectoris who had been successfully treated by thoracoscopic
cardiac sympathectomy was scheduled to have scalp debridement under general
anaesthesia for a scald burn. There were haemodynamic changes during and after
the operation including anaesthetic induction, endotracheal intubation,
maintenance, and early recovery period. The sympathetic denervated heart showed
little chronotropic response to anaesthetic and surgical stimulation. On the
contrary, the parasympathetic response was predominant. An episode of severe
bradycardia occurred during endotracheal suctioning prior to extubation. The
haemodynamic response to cardiac sympathetic denervation corresponded to the
efferent effect of beta-receptor blockade
PMID- 9641385
TI - Quality of life after transthoracic endoscopic sympathectomy for upper limb
hyperhidrosis.
AB - OBJECTIVE: To assess the outcome after transthoracic endoscopic sympathectomy
(TES) for upper limb hyperhidrosis. DESIGN: Prospective cohort study. SETTING:
District general hospital. SUBJECTS: Consecutive patients undergoing TES for
upper limb hyperhidrosis over a fifteen month period. INTERVENTIONS: One-stage
bilateral TES. MAIN OUTCOME MEASURES: Change in quality of life as shown by the
Short Form-36 health assessment questionnaire. RESULTS: Sixteen patients (11
women and 5 men, median age 26 years) underwent operation without complications.
At median follow-up of 6.2 months, symptomatic improvement was found in 26 of 32
limbs treated (82%). Truncal compensatory hyperhidrosis was reported by 13
patients but was severe in only three. There were significant improvements in
social function (p = 0.01) and mental health (p = 0.025) as assessed by the SF
36. CONCLUSION: Despite a high incidence of compensatory hyperhidrosis, TES
improved both the symptoms and overall quality of life in patients with upper
limb hyperhidrosis.
PMID- 9641386
TI - Long-term results of 630 thoracoscopic sympathicotomies for primary
hyperhidrosis: the Vienna experience.
AB - OBJECTIVE: To evaluate of the results of thoracoscopic sympathicotomy for upper
limb hyperhidrosis with a median observation period of more than 15 years.
DESIGN: Retrospective clinical observation study. SETTING: University-affiliated
tertiary referral centre. SUBJECTS: 630 consecutive operations in 352 patients
(median age 30.1 yrs) for primary palmar (68%), axillary (12.7%) and combined
hyperhidrosis (19.3%). INTERVENTIONS: Thoracoscopic sympathicotomy from below T1
to T4 including the fibres of Kuntz using electrocautery through single site
access. MAIN OUTCOME MEASURES: Perioperative success and complication rates (all
patients); long-term follow-up by a questionnaire and/or clinical examination
(83.3% of patients) after a median period of 16 yrs. Calculation of statistical
significance of differences between groups with c2-test. RESULTS: 67.8% of
patients were fully satisfied, 25.7% were partially satisfied and would again
agree to the operation. In 93% the procedure cured hyperhidrosis permanently.
Compensatory and gustatory sweating was observed in 67% and 47% of cases,
respectively. Overall success was significantly (p < 0.001) lower in the group
with axillary hyperhidrosis. Main complications: drainage for pneumothorax 1.3%,
Horner's syndrome in 3.8%, subcutaneous emphysema 2.1%. CONCLUSION: Thoracoscopic
sympathicotomy proved to be highly effective even after long-term follow-up.
Compensatory sweating impairs patients' satisfaction in some cases.
PMID- 9641387
TI - Value of Doppler sonography in the assessment of patients with Caroli's disease.
AB - PURPOSE: We examined the intracystic flow pattern and portal hemodynamics with
Doppler sonography in patients with Caroli's disease. METHODS: Sonographic
characteristics and portal hemodynamics were studied by color Doppler sonography
and spectral analysis in 5 patients (4 children and 1 adult) with Caroli's
disease using high-frequency transducers. Caroli's disease was associated with
infantile polycystic kidney disease in 4 patients and congenital hepatic fibrosis
in 2 patients. Four patients had no clinical or imaging evidence of portal
hypertension. The adult patient had congenital hepatic fibrosis and portal
hypertension. RESULTS: Color Doppler sonograms and spectral analyses disclosed
distinctive hepatic arterial and portal venous flow within the fibrovascular
projections in the bile ducts of all the children. The adult with advanced portal
hypertension presented with a no-flow state in the intracavitary part of the
portal vein and a strong arterial signal related to disturbed hemodynamics in the
arterialized liver. CONCLUSIONS: The fact that portal hemodynamics change over
time should be taken into account when Doppler assessment of Caroli's disease is
attempted. Doppler sonographic monitoring of the portal system to indirectly
diagnose and follow the progression of so-called congenital hepatic fibrosis may
be an effective alternative to liver biopsy.
PMID- 9641388
TI - Sonography of gallbladder abnormalities in acromegaly patients following
octreotide and ursodiol therapy: incidence and time course.
AB - PURPOSE: We studied the effects of octreotide and ursodiol on the gallbladders of
patients with acromegaly. METHODS: We performed gallbladder sonography in
patients with acromegaly at various intervals during treatment. Group I (18
patients) was treated with subcutaneous injections of the somatostatin analogue
octreotide. Group II (10 patients) was treated with ursodiol while receiving
octreotide therapy. RESULTS: Seventy-eight percent of patients receiving
octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi
in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10
patients. CONCLUSIONS: A majority of patients receiving octreotide develop
gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most
cases.
PMID- 9641389
TI - Relationships between echo level and histologic characteristics in small
hepatocellular carcinomas.
AB - PURPOSE: The relationships between ultrasound echo level and histologic
characteristics of hepatocellular carcinomas (HCCs) of 2 cm or less in diameter
were studied. METHODS: The apparent echo level and frequency-dependent
attenuation from the abdominal wall to the tumor and surrounding liver parenchyma
were quantitated on B-mode images using diagnostic ultrasound equipment. The
inherent echo level corrected by the frequency-dependent attenuation was used in
this study. Histologic specimens were collected by sonographically guided small
gauge core-needle biopsy. Increase in deposition of fat and changes in cellular
density and in connective tissue density were evaluated histologically. RESULTS:
From the quantitative comparison of echo levels and histologic characteristics,
it was evident that the deposition of fat caused an increase in echo levels. A
reduction in connective tissue density resulted in a decrease in echo levels in
hypoechoic HCCs, which had no or little fat deposition. CONCLUSIONS: The
estimation of echo level in small HCCs may be useful in predicting the tumors'
histologic characteristics.
PMID- 9641390
TI - Sonographic appearances of small hepatic nodules without tumor stain on contrast
enhanced computed tomography and angiography.
AB - PURPOSE: We report the sonographic appearances and pathologic findings for
hepatic nodules 2 cm or smaller that were detected by sonography but that did not
produce a tumor stain on constrast-enhanced helical CT or digital subtraction
angiography. METHODS: Sixty-six nodules 2 cm or less were found by sonography in
39 patients. Sonographically guided needle biopsies were done on all lesions.
RESULTS: Twenty-seven nodules were benign nodules, 9 were borderline lesions, and
30 were hepatocellular carcinomas. Benign nodules were significantly smaller than
hepatocellular carcinomas (mean size, 1.0 cm versus 1.4 cm, respectively; p
<0.00001). Nodules 1 cm or smaller were more likely to be diagnosed as benign
nodules (68%) than as either of the other types (32%; p = 0.01). A significantly
greater percentage of hepatocellular carcinomas showed a heterogeneous pattern
(64%) on sonography compared with benign nodules (25%) and borderline lesions
(11%; p = 0.04). In nodules 1 cm or smaller, a homogeneous pattern (68%) was more
common than a heterogeneous pattern (32%; p = 0.01). CONCLUSIONS: The nature of
small hepatic nodules cannot be determined with sonography. Thus, biopsy remains
the only technique for obtaining a definitive diagnosis.
PMID- 9641391
TI - Sonographic findings in noncirrhotic portal fibrosis.
AB - PURPOSE: The aim of this study was to evaluate the sonographic appearances of
noncirrhotic portal fibrosis (NCPF). METHODS: Between 1983 and 1996, 12 patients
between the ages of 16 and 60 years were diagnosed with NCPF on the basis of
medical history and clinical, imaging, and biopsy findings. RESULTS: Sonograms
for all patients showed hyperechoic bands surrounding the portal vein branches,
which were separated from adjacent liver parenchyma by a hypoechoic stripe. All
liver biopsy specimens showed nonspecific changes and no cirrhosis. Histologic
findings included fibrosis and some obliteration of the intrahepatic portal
veins. CONCLUSIONS: If sonography of the liver shows increased echogenicity of
the walls of the portal vessels with a hypoechoic stripe between the wall and the
adjacent liver parenchyma in a patient who has portal hypertension and normal
liver function tests, NCPF should be considered.
PMID- 9641392
TI - Fetal hydrops in the first trimester associated with maternal parvovirus
infection.
AB - We present a case of fetal hydrops associated with maternal parvovirus infection
during the first trimester of pregnancy that sonographically mimicked findings
associated with fetal aneuploidy. The transabdominal sonograms of this fetus at
12.9 weeks' gestational age were consistent with increased nuchal translucency
thickness. Transvaginal sonographic evaluation of the fetus showed generalized
subcutaneous sonolucency suggestive of early fetal hydrops. An etiologic
evaluation identified serologic evidence of recent maternal parvovirus infection
and a normal karyotype. The pregnancy ended in fetal demise. Our findings suggest
that visualization of nuchal translucency thickening in the first trimester
should prompt a complete sonographic evaluation for fetal hydrops, which, if
identified, should lead to serologic evaluation for parvovirus infection.
PMID- 9641393
TI - Cervical varices: an unusual etiology for third-trimester bleeding.
AB - We report an unusual etiology for third-trimester bleeding. A pregnant patient
underwent sonographic evaluation after presenting in the third trimester with
uterine contractions and bleeding per the vagina. Massive cervical varices were
identified on prenatal sonography as the cause of the bleeding and resulted in
cesarean delivery and gravid hysterectomy. Cervical varices may result in
significant maternal morbidity despite prenatal diagnosis.
PMID- 9641394
TI - Intra-abdominal lymphangioma in a newborn.
AB - We report the case of a male newborn infant with an intra-abdominal cavernous
lymphangioma that produced acute abdominal symptoms. Sonography showed a cystic
mass with thin septations, which caused intestinal obstruction and stenosis of
the iliac artery. The histologic findings after surgical resection reflected the
sonographic appearance of the mass. The differential diagnosis of cystic
abdominal lesions is discussed. Sonography is the preferred method of diagnosis.
PMID- 9641395
TI - Duplicate origin of left vertebral artery with thrombosis at the origin: color
Doppler sonography and CT angiography findings.
AB - We describe a rare case of vertebral artery duplication in a patient with
vertigo, weakness, and nausea. A color Doppler examination revealed a duplicate
origin of the left vertebral artery and a hyperechoic thrombus at the origin of 1
of the duplicated arteries. CT angiography of the lower neck area demonstrated
duplicated vertebral arteries on the left side. MR angiography of the
vertebrobasilar system did not show duplication, indicating that the duplicated
vertebral arteries fused at a level higher than C2.
PMID- 9641396
TI - Segmental hemorrhagic infarction of testis associated with epididymitis.
AB - Testicular infarction is most commonly associated with acute testicular torsion.
We present the sonographic findings in a case of segmental testicular infarction
associated with epididymitis. The gray-scale abnormalities included a round, well
defined, hypoechoic intratesticular mass and heterogeneity and enlargement of the
epididymis. Color Doppler sonography demonstrated only minimal blood flow in the
intratesticular mass and increased flow in the epididymis. Recognition of acute
testicular segmental infarction as a complication of epididymitis may prevent
unnecessary orchiectomy.
PMID- 9641397
TI - Localized painful giant-cell thyroiditis without inflammatory signs in a
euthyroid patient followed by serial sonography.
AB - We describe a patient with localized painful giant-cell thyroiditis. A 45-year
old woman noticed a tender lump in the left side of the neck. Sonography of the
thyroid revealed diffuse swelling of the left lobe with irregular hypoechoic
areas. Three months later, the tender swelling subsided, and the hypoechoic areas
disappeared without any treatment. There were never any systemic signs of
inflammation or thyroid dysfunction. Atypical localized subacute thyroiditis was
considered to be the most probable diagnosis based on fine-needle aspiration
cytology and serial sonography. Serial sonographic evaluations are useful to
avoid unnecessary surgery.
PMID- 9641398
TI - Effects of active noise reduction on noise levels at the tympanic membrane.
AB - BACKGROUND: Active noise reduction (ANR) is an electronic system that works by
continuous sampling of noise inside the earshell of the headset with a small
microphone. This signal is inverted in phase through the headset speaker, thus
reducing noise levels by destructive interference of the acoustic field. The
system provides good low-frequency noise attenuation, but aircrew differ in their
subjective opinion of ANR. The present study is an attempt to provide an
objective assessment of the effect of ANR on noise levels at the tympanic
membrane. METHODS: There were 7 subjects with normal ears who were placed in an
environment of recorded noise from a BO-105 helicopter. A microphone probe was
inserted to within 5 mm of the tympanic membrane of each subject's right ear.
Noise levels in the ear were measured without a headset and with two different
ANR headsets. Measurements were performed with and without the ANR system on, and
with and without white noise through the headset communication system. The white
noise was used to simulate aircraft communication noise. RESULTS: The two
headsets tested had differing levels of passive and active attenuation. The ANR
system produced a substantial low-frequency attenuation. However, noise levels in
the mid frequencies increased somewhat when the ANR system was switched on. This
effect was augmented when white noise in the communications system was
introduced, particularly for one of the two headsets. Low-frequency noise
attenuation of ANR systems is substantial, but an increased mid- and high
frequency noise level caused by the ANR may affect both communication and overall
noise levels. Our data provide advice on what factors should be taken into
account when ANR is evaluated for use in an aviation operational environment.
PMID- 9641399
TI - Auditory event-related potentials and reaction time during decompression from
hyperbaric trimix conditions.
AB - BACKGROUND: Auditory event-related potentials (ERP) and sensomotor reaction time
(RT) were investigated in divers during decompression from hyperbaric trimix
conditions in order to assess the auditory information processing of the divers.
METHODS: Two passive series, 30 low (800 Hz) and 30 high (1200 Hz) tones were
presented as well as one simple reaction task (SRT) and one choice reaction task
(CRT) series. In both task series, the subjects were instructed to press the
button as quickly as possible with the right-hand thumb after a low tone was
heard. The individual analyses of the decompression period ERPs and RT data were
compared with the pre-diving results for the series. RESULTS: Despite the
interindividual differences, the sensomotor reactions were retarded during the
decompression period, most clearly in the CRT. A prolongation of the N2 and P3
latency in this series gives grounds to accept that a cognitive slowing takes
part in the longer reaction times during decompression. The slowing of the
auditory information processing during decompression manifests with task
manipulation difficulties.
PMID- 9641400
TI - Intrasynaptosomal free calcium and nitric oxide metabolism in central nervous
system oxygen toxicity.
AB - BACKGROUND: Central nervous system (CNS) oxygen (O2) toxicity is complex, and the
etiology of its most severe manifestation, O2 convulsions, is yet to be
determined. A role for nitric oxide (NO) has been proposed, although recent data
have indicated that NO is synthesized from L-arginine by an enzyme, NO synthase
(NOS). The enzyme is dependent on free calcium (Ca2+) concentration, therefore
increases in intracellular Ca2+ may constitute the physiological and
pathophysiological mechanisms for stimulating the synthesis of NO. METHODS: In
this study, the intrasynaptosomal free calcium concentration ([Ca2+]i) was
measured by the fluorescence of fura-2/AM, and cGMP (as an indirect marker of NO
levels) was by radioimmunoassay (RIA) in the rat hippocampus after hyperbaric
oxygen (HBO) exposure. We also investigated the effects of daurisoline (DSL,
calcium channel blocker) and N-nitro-L-arginine (LNNA, NOS inhibitor) on the
above biochemical parameters and the development of oxygen toxicity. RESULTS: The
results show that when the rats were exposed to HBO at 0.5 MPa the
intrasynaptosomal Ca2+ and cGMP levels increased by two and three times,
respectively, whereas with the use of DSL prior to HBO, the accumulation of
[Ca2+]i and cGMP dropped to 56% and 60%, correspondingly. In the rats medicated
with LNNA prior to HBO. [Ca2+]i and cGMP levels dropped to 70% and 36% of the HBO
group. At the same time, the appearance of CNS oxygen toxicity was delayed and
the survival rate increased. The protective effects of LNNA were reversed by L
arginine pretreatment. These findings suggest that the neuronal Ca2+ overload
during HBO exposure is a major factor in the pathogenesis of CNS O2 toxicity, and
cGMP-NO pathways may be directly involved in HBO-induced seizures.
PMID- 9641401
TI - Subject's perceptions of the crew interaction dynamics under prolonged isolation.
AB - BACKGROUND: The interactions of individuals participating in space simulation
studies can give us valuable information about ways that space crew members
relate with one another. A promising method of investigating such interactions is
based on the Kelly repertory grid technique. HYPOTHESES: We predicted that in a
space simulation crew: 1) one's personal self-concept would become closer to
concepts about other crew members in a cohesive crew, and vice-versa, and 2) the
similarity of one's ego images in the past, present and future influences that
person's position in the group. METHOD: Crews from two isolation studies lasting
135 and 90 days at the Institute for Biomedical Problems in Moscow were evaluated
using a modification of the Kelly repertory grid technique. Members assessed each
other on a monthly basis and during off-nominal simulated docking periods.
RESULTS: During both isolations, crew members were unsuccessful in making their
personal self-concepts move closer to their concepts about fellow crew members.
Crew disintegration resulted, with one member becoming an outsider whose
personality was characterized by a disintegrated ego-image and an infantile type
of the present ego. CONCLUSIONS: In small isolated groups, failure to make
personal self-concepts become more like concepts about other crew members can
lead to group disintegration and tension and can result in the appearance of an
outsider who has a disintegrated ego-image and an infantile present ego.
PMID- 9641402
TI - Overtraining parameters in special military units.
AB - BACKGROUND: Previous studies have shown the diagnostic relevance of the so-called
free testosterone/cortisol ratio (FTCR). A condition of overtraining might indeed
exist in an athlete when at least one of the two following criteria are observed:
a) a FTCR value lower than 0.00035 (FT in nmol x L(-1) and C in micromol x L(
1)); and b) a decrease in the FTCR of 30% or more. On the other hand, no previous
research has studied the incidence of overtraining in special military units as a
result of their demanding training programs. HYPOTHESIS: A percentage of recruits
of the Spanish special military Unit, "Grupo de Operaciones Especiales," (GOES)
might be overtrained. It was the purpose of our study to analyze the effects on
the FTCR of an intense physical training program performed by recruits of the
GOES. METHODS: Before (PRE) and after (POST) an 8-wk training program,
respectively, the following measurements were made in 42 recruits of the GOES:
hematological and hormonal parameters (FTCR), aerobic and anaerobic tests, and
strength and power tests. RESULTS: A high incidence (10 subjects, 23.8% of total)
of overtraining existed among conscripts, as determined by the absolute criterium
of a decline in the FCTR of 30% or more when comparing PRE and POST values.
Additionally, overtraining was associated with a decrease in performance (i.e.,
isometric strength, vertical jump, Wingate tests). CONCLUSIONS: In addition to
some conventional measurements of performance, the FTCR might be used to monitor
exercise training in military units, in order to prevent overtraining.
PMID- 9641403
TI - Flight performance effects of thermal stress and two aviator uniforms in a UH-60
helicopter simulator.
AB - The effects on flight performance of the four combinations of an unencumbered
mission oriented protective posture (MOPP) aviator battle dress uniform (ABDU)
and encumbered MOPP4 over ABDU flight ensemble in cool (70 degrees F or 21.1
degrees C, 50% relative humidity [RH]) and hot (100 degrees F or 37.8 degrees C,
50% RH) UH-60 simulator cockpit conditions were evaluated with a repeated
measures, 2 x 2 factorial study using nine crews. The encumbered MOPP4 uniform
had the most frequent adverse effect on flight performance followed by heat
stress, with less frequent effects from the combination or interaction of these
two factors. This study confirmed that heat stress and wearing an encumbered U.S.
Army MOPP4 flight uniform significantly reduced endurance and flight performance
in a UH-60 simulator.
PMID- 9641405
TI - Effects of hypergravity on optokinetic after-nystagmus and perceived direction of
optokinetic stimulation.
AB - BACKGROUND: Previous observations made in parabolic flight and centrifuge studies
have shown the presence of a vertical nystagmus (Lz-nystagmus) induced by changes
in gravitoinertial forces, and its interaction with oculomotor reflexes.
HYPOTHESIS: This Lz-nystagmus is also responsible for the changes in optokinetic
after-nystagmus (OKAN) and the subjective perception of optokinetic stimulation
direction during hypergravity. METHODS: OKAN was recorded during the 1.8-g phase
of parabolic flight after exposure to horizontal or vertical optokinetic
stimulation during the preceding 1.0-g or 0-g phases. Changes in the apparent
direction of image motion in subjects presented with an optokinetic stimulus were
investigated in another experiment where longer exposure to hypergravity was
generated by flying an airplane along a spiral path. RESULTS: In upright
subjects, the time constant of OKAN with slow phase up decreased during 1.8 g,
whereas the horizontal OKAN showed no change in 1.8 g compared with OKAN recorded
in 1.0 g. When the subjects were lying on their left side, the OKAN with slow
phase right (slow phase up with respect to gravity) decreased in 1.8 g. The
subjects tested showed larger error in setting the optokinetic stimulus in a pure
horizontal plane in 1.8 g than in 1.0 g. The error was also larger for oblique
stimulus in 1.8 g than in 1.0 g, but no differences were seen for the vertical
stimulation. CONCLUSION: The changes in OKAN can be explained by an interaction
between slow phase eye movements generated by OKAN and the Lz-nystagmus generated
by change in the gravitational force level. The error of the perceived direction
of the optokinetic stimulus measured during horizontal and oblique stimulation is
also presumably due to the interaction between the visual system and the Lz
nystagmus generated by hypergravity.
PMID- 9641404
TI - Ethanol ingestion prolongs orthostatic intolerance in hyperthermic humans.
AB - BACKGROUND: Both ethanol ingestion and hyperthermia contribute to orthostatic
intolerance (OI). HYPOTHESIS: Since ethanol has been cited as a major risk factor
for hyperthermia-related deaths, we hypothesized that ethanol exacerbates OI
induced by hyperthermia. METHODS: There were seven subjects (four males, three
females) rendered hyperthermic (esophageal temperature = 39 degrees C) in a 40
degrees C water bath on two separate days: Condition 1) Control (juice
ingestion); and Condition 2) Ethanol [ethanol (1 ml x kg(-1) body mass) and juice
ingestion]. To test for OI, 5-min supine periods were followed by 5-min 63
degrees head-up tilts prior to and following immersion. BPs, heart rate and
esophageal temperatures were monitored throughout the experiments. RESULTS: For
first and second post-immersion tilts, mean arterial BP (MAP) during tilting
increased by 5.9 +/- 3.6 (SE) and 9.8 +/- 2.6 mm Hg in the control condition,
while it decreased by 7.9 +/- 5.8 and 0.6 +/- 4.3 mm Hg in the ethanol condition.
This gave significantly lower MAP (ethanol vs. control) of 63.6 +/- 3.1 vs. 71.8
+/- 4.5 mm Hg (p < 0.05) for the first and 79.6 +/- 2.3 vs. 86.7 +/- 4.4 mm Hg (p
< 0.05) for the second post-immersion tilts. These values were all significantly
less (p < 0.05) than normothermic tilted values of 94.7 +/- 4.7 mm Hg in the
ethanol and 93.6 +/- 2.9 mm Hg in the control condition. Prior to warm water
immersion, subjects tolerated all head-up tilts. In the control condition, only
one subject experienced orthostatic intolerance following the first post-heating
tilt and no intolerance was experienced following 30 min post-heating. However,
during the ethanol condition, 4 subjects experienced orthostatic intolerance
following the first tilt with episodes of intolerance lasting as long as 80 min
(8 supine/tilt cycles). CONCLUSION: Ethanol ingestion prolonged and increased the
magnitude of OI in hyperthermic subjects. This may at least partly explain why
ethanol is a major risk factor in hyperthermia-related deaths.
PMID- 9641406
TI - Effects of hypobaric hypoxia on postural control.
AB - BACKGROUND: While the effects of accelerative forces on the vestibular system
have been thoroughly investigated, the effects of hypobaric conditions on the
postural system have attracted less attention. The purpose of the study was to
investigate if postural control is affected by hypobaric hypoxia. HYPOTHESIS:
Moderate hypobaric hypoxia may reduce postural control. METHODS: Subjective and
multiple objective measurements of postural control with open and closed eyes
were made in 16 military aircrew standing on a static balance platform before,
during, and after exposure to an altitude chamber training profile with a maximum
altitude of 25,000 ft. RESULTS: No subjective dizziness and no clinical
unsteadiness were noted. However, significant changes in body sway were found at
the balance platform during hypobaric exposure at 18,000, 14,000 and 8000 ft
compared with the baseline registrations. The relative increase in sway movements
was greater in the eyes open condition compared with the eyes closed condition,
and significant for movements in the anteroposterior plane but not in the lateral
plane. Most sway parameters returned to pre-exposure values on return to ground
level. CONCLUSIONS: Acute hypobaric hypoxia, corresponding to the tested
altitudes, influenced postural control primarily in the anteroposterior plane
with eyes open. This is in agreement with other studies showing that vision is
the first of the special senses to be altered by lack of oxygen.
PMID- 9641407
TI - Sleep and wake patterns in aircrew on a 2-day layover on westward long distance
flights.
AB - BACKGROUND: As part of a research program of sleep/wake disturbances in
connection with irregular work hours and time zone transitions, the study aimed
to describe the spontaneous sleep/wake pattern in connection with a westward
(Stockholm to Los Angeles) transmeridian flight (-9 h) and short layover (50 h).
HYPOTHESIS: To describe all sleep episodes and the recovery process across 4 d,
and to relate adjustment to individual differences. METHODS: We monitored 42 SAS
aircrew for 9 d with activity monitors and diary before, during, and after
flight. RESULTS: During the outbound day the wake span was 21.7 h and 90% of the
aircrew adopted local bed times on layover. The readaptation to normal sleep/wake
patterns were rapid on the return. Napping was common (93%), especially on-board
and before the return. Sleep efficiency dropped below 90% during layover, being
felt to be too short and disturbed by awakenings, and gradually returned to
normal across four recovery days. Recovery sleep was characterized by
difficulties waking up and feelings of not being refreshed from sleep. Sleepiness
symptoms increased during layover and gradually decreased across recovery days,
still being elevated on day 4. CONCLUSIONS: In the present study we found that
westward flights are associated with extended wake spans during layover,
increased sleepiness, and slow recovery on return home. Strategic sleeping may
counteract the effect somewhat, but individual differences are few.
PMID- 9641408
TI - Altitude-induced migraine headache secondary to pravastatin: case report.
AB - A 46-yr-old airline captain with many exposures to altitude chamber, fighter, and
airliner flight developed migraine-type headaches after exposure to cabin
altitudes above 6,000 feet. He had no prior history of chronic headaches or
migraine. Symptoms began within days of starting pravastatin for
hypercholesterolemia, but had not occurred during 4 yr of treatment with
lovastatin. Headache intensity related directly to increasing pressure altitudes
above 6,000 ft for periods of time greater than 45 min. Descent below 5,000 ft
cabin altitudes relieved headaches. Exposure to barometric pressure changes has
been associated with migraine headache. Vascular headaches are also a prominent
feature of acute mountain sickness. Although the HMG-CoA reductase inhibitors are
reported to be associated with increased occurrence of headache, the mechanism is
poorly understood. Migraine headaches may be triggered in previously asymptomatic
individuals by unique combinations of trigger factors. However, there have been
no prior reports of migraine headaches triggered by the combined exposure to
pravastatin and reduced barometric pressure.
PMID- 9641409
TI - "First do no harm": the role of defibrillators and advanced medical care in
commercial aviation.
PMID- 9641410
TI - Smart Aircrew Integrated Life Support System.
PMID- 9641411
TI - Refractive surgery: are there any limits?
PMID- 9641412
TI - The adjustable refractive surgery concept (ARS)
PMID- 9641413
TI - Corneal or lens refractive surgery?
PMID- 9641414
TI - Phakic intraocular lenses. Are the sirens singing again?
PMID- 9641415
TI - Will some see the future through phakic intraocular lenses?
PMID- 9641416
TI - Into thin air with phakic intraocular lenses?
PMID- 9641417
TI - Comparison of refractive corneal surgery and phakic IOLs.
PMID- 9641418
TI - Surf's up...catch a wave with the waterjet.
PMID- 9641419
TI - Angle-fixated anterior chamber phakic intraocular lens for myopia of -7 to -19
diopters.
AB - PURPOSE: To assess the safety and efficacy of a second generation, anterior
chamber phakic intraocular lens (Baikoff Model ZB5M) in patients with high
myopia. METHODS: One hundred and twenty-one patients (134 eyes) with myopia of
7.00 to -18.80 D were implanted with the ZB5M lens and followed for 18 to 52
months; the number of eyes evaluated was: 6 months (104 eyes), 1 year (91 eyes),
18 months (78 eyes), 2 years (68 eyes), and 3 years (35 eyes). RESULTS:
Postoperative spherical equivalent refraction averaged -1.00 D and the error in
refractive correction (achieved minus intended) averaged -0.40 D during the first
2 years, increasing -to -1.30 D refraction and -0.60 D error in refractive
correction at 3 years. At 2 years, approximately 40% of eyes had a spherical
equivalent refraction within +/-0.50 D, and 65% within +/-1.00 D. The uncorrected
distance visual acuity was 0.048 at baseline and 0.5 at 3 years; near visual
acuity was 0.21 at baseline and approximately 0.7 over the 3 years of follow-up.
Spectacle-corrected distance visual acuity at baseline was 0.54; it improved to
0.7. Near visual acuity was 0.65 at baseline and it improved to approximately
0.75. Endothelial cell counts in the central and peripheral cornea were reduced
by an average 3.3% at 6 months, declining an additional 1% to 2% over the
remaining follow-up period. Regression analyses indicated that most of the
endothelial cell loss was due to surgery. Additional complications included
halos/glare in 37 of 133 eyes (27.8%) and iris retraction with pupillary
ovalization in 30 of 133 eyes (22.6%). The intraocular lens was exchanged in four
of 133 eyes (3.0%) and removed in three of 133 eyes (2.3%), the latter because of
halos (one eye) and a flat anterior chamber with severe inflammation (two eyes).
CONCLUSIONS: Implantation of the Baikoff ZB5M lens in the anterior chamber of
phakic eyes significantly reduced high myopia and produced a stable refractive
outcome over the 3 years, accompanied by marked improvement in uncorrected
distance visual acuity and minimal, non-progressive damage to the corneal
endothelium. Frequent complications included pupillary ovalization and
halos/glare. Improvements in accuracy of IOL power calculations are needed.
PMID- 9641420
TI - Posterior chamber phakic intraocular lens for myopia of -8 to -19 diopters.
AB - PURPOSE: To examine the efficacy, predictability, stability, and safety of
posterior chamber phakic intraocular lens (IOL) implantation in patients with
extreme myopia. METHODS: We analyzed the results of 124 eyes that received a
posterior chamber hydrogel collagen plate phakic IOL (Staar Collamer Implantable
Contact Lens, ICL) for the correction of their myopia. The target postoperative
spherical equivalent refraction was emmetropia. Mean follow-up was 11 months
(range 1 to 36 mo). RESULTS: The mean preoperative spherical equivalent
refraction was -13.38 +/- 2.23 D (range, -8.50 to -18.63 D). Mean postoperative
spherical equivalent refraction at last examination was -0.78 +/- 0.87 D (range,
+1.63 to -3.50 D), with 69% (86 eyes) within +/-1.00 D and 44% (55 eyes) within
+/-0.50 D of emmetropia. The refraction remained stable with a statistically
insignificant change (p > 0.05 at each interval) during follow-up. A gain of two
or more lines of spectacle-corrected visual acuity was seen in 36% (45 eyes) at
last examination. One eye (0.8%) lost two or more lines of spectacle-corrected
visual acuity from a retinal detachment. CONCLUSION: Posterior chamber phakic IOL
implantation with the Staar Collamer plate lens is an effective and safe method
for reducing or correcting myopia between -8 and -19 D. Gains in spectacle
corrected visual acuity were common, and results suggested good refractive
stability. Improvements in phakic IOL power calculation formulas are needed to
improve the predictability of refractive outcome.
PMID- 9641421
TI - Posterior chamber phakic intraocular lens for hyperopia of +4 to +11 diopters.
AB - PURPOSE: To examine the efficacy, predictability, stability, and safety of
posterior chamber phakic intraocular lens (IOL) implantation in eyes with high
hyperopia. METHODS: We analyzed the results of 24 eyes that received a posterior
chamber hydrogel-collagen plate phakic IOL (Staar Collamer Implantable Contact
Lens, ICL) for the correction of hyperopia with the goal of emmetropia. Mean
follow-up was 8.4 months (range, 1 to 18 mo). RESULTS: The mean preoperative
spherical equivalent refraction was +6.51 +/- 2.08 D (range, +3.75 to +10.50 D).
Mean postoperative spherical equivalent refraction at last examination was -0.39
+/- 1.29 D (range, +1.25 to -3.88 D), with 79% (19 eyes) within +/-1.00 D and 58%
(14 eyes) within +/-0.50 D of emmetropia. Postoperative uncorrected visual acuity
at last examination was 20/20 or better in 8% (two eyes) and 20/40 or better in
63% (15 eyes). A gain of two or more lines of spectacle-corrected visual acuity
was seen in two eyes (8%) at last examination. One eye (4%) lost two or more
lines of spectacle-corrected visual acuity due to progressive neovascular
glaucoma initiated by early postoperative pupillary block. CONCLUSION: Posterior
chamber phakic IOL implantation with the Staar Collamer plate lens is an
effective method for correcting high hyperopia. Large, patent iridotomies are
important in hyperopic eyes to lower the risk of postoperative pupillary block.
Improved phakic IOL power calculation formulas will refine predictability of
refractive outcome.
PMID- 9641422
TI - Iatrogenic keratectasia after laser in situ keratomileusis.
AB - BACKGROUND: Lamellar refractive surgery reduces the biomechanical strength of the
cornea which may lead to mechanical instability and keratectasia. METHODS: Three
eyes had laser in situ keratomileusis (LASIK) for myopia from -10.00 to -13.50 D.
The procedures were performed with two different wide-field excimer lasers and
two different microkeratomes. The patients were followed up to 1 year after
surgery. RESULTS: Central steep areas developed between 1 and 8 months after
surgery. In contrast to conventional central steep islands, these showed rapid
progression and were interpreted as keratectasia. CONCLUSION: Iatrogenic
keratectasia represents a complication after LASIK that may limit the range of
myopia correction. Based on biomechanical considerations we recommend a residual
corneal thickness of the stromal bed of at least 250 microm.
PMID- 9641423
TI - Five and three year follow-up of photorefractive keratectomy for myopia of -1 to
6 diopters.
AB - BACKGROUND: To report the 5 and 3 year results of photorefractive keratectomy for
-1 to -6 D of myopia and less than 1.50 D astigmatism. METHODS: All eyes were
treated with a VISX 20/20 excimer laser with an ablation diameter of 5 mm. Our
initial series of 133 eyes were treated in four groups: IIA, IIB, III and III No
Nitrogen and reported on previously with follow-up from 6 to 36 months. The
present report extends the observation period to 3 and 5 years for 114 eyes.
RESULTS: Groups IIA and IIB were followed for 5 years and Groups III and III No
Nitrogen for 3 years. Group IIA achieved 77% (10 of 13 eyes) +/-1.00 D (54%
within +/-0.50 D) of emmetropia with stability from 6 months and 54% (seven of 13
eyes) had visual acuity of 20/20 or better. In Group IIB, 35% (six of 17 eyes)
were +/-1.00 D (18% within +/-0.50 D) of emmetropia and stable from 18 months.
Two of 17 eyes (12%) had 20/20 or better visual acuity. Group III had 76% (42 of
55 eyes) within +/-1.00 D (51% within +/-0.50 D) of emmetropia with stability
after 12 months; 60% (33 of 55 eyes) had 20/20 or better visual acuity. Group III
No Nitrogen had 73% (11 of 15 eyes) within +/-1.00 D (60% within +/-0.50 D) of
emmetropia and were stable after 6 months; 47% (seven of 15 eyes) had 20/20 or
better visual acuity. There was no hyperopic refractive shift. No correlation was
found between the percent of correction achieved and preoperative amount of
myopia, age, or sex. CONCLUSION: Refractive stability was achieved from 6 to 12
months in most eyes; a few required 18 months to stabilize. Groups IIA and III
continued to be stable; Groups HB and III No Nitrogen showed mild regression that
was not statistically significant.
PMID- 9641424
TI - Unilateral refractive keratotomy for anisometropia.
AB - BACKGROUND: In anisometropia, the asymmetry of refractive error produces
disparity of image magnification (aniseikonia) that can create visual discomfort,
especially when asymmetry is 3.00 diopters or more. METHODS: A prospective study
of 20 eyes of 20 patients between 18 and 61 years of age who underwent unilateral
radial and/or transverse keratotomy was conducted; results of at least 12 months
follow-up are presented. The efficacy of keratotomy was evaluated by the
following criteria: 1) change in spherical and cylindrical refraction, 2)
decrease in refraction difference between two eyes of each patient, 3) change in
spectacle-corrected visual acuity, and 4) change in binocular vision functions
and asthenopic complaints. RESULTS: Mean decrease in spherical refractive error
was 3.66 +/- 1.58 D (range, 1.25 to 7.50 D) and 2.08 +/- 0.81 D (range, 1.00 to
3.50 D) in astigmatic refraction. The mean refraction difference between two eyes
was 4.90 +/- 2.20 D preoperatively, and this difference regressed to 1.79 +/-
1.42 D postoperatively. Spectacle-corrected visual acuity increased in seven eyes
(35%), remained the same in 12 eyes (60%) and decreased in one eye (5%). All
patients reported relief of asthenopic complaints. Fusion amplitudes increased in
12 (60%) patients. Stereoscopic vision improved in five (25%) patients.
CONCLUSION: Monocular refractive keratotomy can significantly decrease
anisometropia.
PMID- 9641425
TI - Measurement of radial keratotomy clear zone diameters.
AB - BACKGROUND: To compare the accuracy of photographic measurements to slit-lamp
measurements of radial keratotomy clear zone diameters in order to develop an
independent, objective, unbiased, and reproducible method of verifying clinical
observations. METHODS: Twenty-five patients (48 eyes) following radial keratotomy
had matched slit-lamp and photographic measurements of the diameter of the
central clear cornea between the ends of opposite radial incision pairs. Matched
slit-beam, photographic, and pathologic observations were compared statistically.
RESULTS: Two hundred fifty-four slit-lamp clear zone diameter measurements were
obtained. In twenty instances (8%), the radial incision end-point could not be
identified on the photograph. For the remaining 234 measurements, the mean slit
lamp clear zone diameter was statistically smaller than the photographic
measurement by 0.03 mm (t-test, p = 2.2 x 10(-5)). The slit-lamp and photographic
clear zone measurements were strongly positively correlated (Pearson r = 0.99, p
< 1.0 x 10(-15)). Matched slit-lamp, photographic, and pathologic clear zone
measurements (N=8) in one excised corneal button were not statistically
different. CONCLUSIONS: For radial keratotomy clear zone diameters, slit-beam
measurements and photographic caliper measurements yield indistinguishable
results that are highly concordant over a wide range of diameters. Both slit-beam
and photographic measurements yield accurate and reliable results that reflect
the true pathologic achieved clear zone diameter following radial keratotomy
surgery.
PMID- 9641426
TI - Principles and microscopic confirmation of surface quality of two new waterjet
based microkeratomes.
AB - PURPOSE: The HydroBlade and the HydroBrush keratomes are waterjet-based devices
for corneal surgery that operate at normal intraocular pressure in two different
modes: removal of parallel or shaped lenticules or hinged flaps with a small
diameter, high speed waterjet; and removal of the epithelium with a waterjet
sheet. The operating principles as well as histology of the cut surfaces are
described. METHODS: A flap was made in one cadaver eye with a Chiron ACS keratome
and in the second eye with the HydroBlade keratome. The epithelium was removed in
one cadaver eye with a surgical blade and in the second eye by the HydroBrush
keratome. Scanning and transmission electron microscopy and light microscopy was
obtained. RESULTS: The HydroBlade keratome cleaved only cross-linking fibrils and
left intact keratocytes. Shape and dimensions of the flap were accurate. There
was no observable hydration or significant heating of the tissue. Mechanical
forces on the cornea were small. The HydroBrush keratome removed the epithelium
quickly, left no epithelial debris, and did not damage Bowman's layer.
CONCLUSION: With the HydroBlade keratome, the cuts are ideal blunt dissections.
Epithelial removal with the HydroBrush keratome is effective and quick.
PMID- 9641427
TI - Hydroepithelial keratectomy in rabbits with a waterjet-based instrument.
AB - BACKGROUND: Corneal epithelial removal finds multiple applications in ophthalmic
surgery (epithelial herpes infections, recurrent epithelial erosion, corneal
ulcers and plaques, and intraoperative epithelial clouding). Photorefractive
keratectomy is initiated by removal of the epithelium. Current techniques for
epithelial removal are suboptimal. We studied the safety and effectiveness of a
new technique, hydroepithelial keratectomy, performed with the HydroBrush
keratome on live rabbits. METHODS: Eighteen rabbits (18 eyes) underwent
hydroepithelial keratectomy and 18 rabbits (18 eyes) underwent epithelial removal
with a surgical blade (blade group). Twelve rabbits were euthanized immediately
after the procedure. Twenty-four rabbits were followed for up to 120 hours after
treatment. Ultrastructural analysis was performed with light and electron
microscopy. RESULTS: The hydroepithelial keratectomy group healed a mean 53 hours
after treatment; the blade group healed a mean 78 hours after treatment. The
HydroBrush keratome exposed the basement membrane and the basal cell membrane of
the epithelium. The blade exposed patches of basement membrane, as well as stroma
and cell debris. CONCLUSIONS: Hydroepithelial keratectomy with the HydroBrush
keratome is effective and safe. Wound healing after hydroepithelial keratectomy
is faster than after blade removal. Unlike the blade, the HydroBrush keratome
exposed a smooth surface, devoid of debris, with well-defined edges and round
shape without hydration nor dehydration of the tissue.
PMID- 9641428
TI - Mycobacterium chelonae keratitis following laser in situ keratomileusis.
AB - Corneal infection after laser in situ keratomileusis (LASIK) is rare. However,
surgical trauma or breakdown of epithelium increases the risk of surface
infection. We present the case of a 45 year old woman who developed keratitis due
to Mycobacterium chelonae 1 month after LASIK with the Mini-Laser Sight 2000
excimer laser. After an initial improvement following antibiotic therapy the
infection progressed until it was necessary to perform penetrating keratoplasty,
with a successful result.
PMID- 9641429
TI - Contrast sensitivity and glare disability after radial keratotomy and
photorefractive keratectomy.
PMID- 9641430
TI - The prediction of surgically induced refractive change from corneal topography.
PMID- 9641431
TI - Allergic conjunctivitis as a risk factor for regression and haze after
photorefractive keratectomy.
PMID- 9641432
TI - Patellar tendon ultrasonography in asymptomatic active athletes reveals
hypoechoic regions: a study of 320 tendons. Victorian Institute of Sport Tendon
Study Group.
AB - OBJECTIVE: To compare patellar tendon sonographic findings in active, currently
asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross
sectional cohort study with convenience control sample. SETTING: The Victorian
Institute of Sport Tendon Study Group, an institutional elite athlete study group
in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female
athletes from the sports of basketball, cricket, netball, and Australian rules
football. Forty athletes who had current symptoms of jumper's knee were excluded
from analysis, leaving 320 subject tendons in athletes who were currently
asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN
OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the
dimensions of subject tendons and noted the presence or absence of hypoechoic
regions and tendon calcification. Dimensions of hypoechoic regions were measured,
and approximate cross-sectional areas were calculated. Chi-squared analysis was
used to test the prevalence of hypoechoic regions in subjects and controls and
men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions
were more prevalent in athlete tendons (22%) than in controls (4%), in male
subject tendons (30%) than in female subjects (14%), and in basketball players
(32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities
were equally prevalent in men and women but more prevalent in basketball players
(15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were
present in 35 of 250 (14%) patellar tendons in athletes who had never had
anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas
were present in asymptomatic patellar tendons of a proportion of elite athletes
but rarely present in controls. This has implications for clinicians managing
athletes with anterior knee pain.
PMID- 9641433
TI - The effectiveness of topical diclofenac for lateral epicondylitis.
AB - INTRODUCTION: Gastrointestinal upset and local pain commonly limit the use of
oral nonsteroidal anti-inflammatory drugs and corticosteroid injection as
treatments for lateral epicondylitis. Transdermal administration of an anti
inflammatory drug could avoid these adverse effects. PURPOSE: To determine the
effectiveness of topical diclofenac as a treatment of lateral epicondylitis.
METHODS: A convenience sample of 14 subjects meeting clinical criteria of chronic
lateral epicondylitis participated in this randomized, double blind, crossover
study. Each subject applied a pluronic lecithin liposomal organo-gel (PLO) over
the affected lateral elbow three times daily for I week, followed by a 1-week
"washout" period of no gel. A second topical PLO gel was then applied similarly
for 1 week. Both gels were identical, but only one gel contained 2% diclofenac.
Treatment order was randomized, and both the subject and tester were blinded.
Pain and isometric wrist extension strength were measured using a visual analog
pain scale (VAS) and a mounted manual muscle testing dynamometer, respectively,
at the following time periods: just before application of the first gel, the last
day of using the first gel, the last day of the washout week, and the last day of
using the second gel. Analysis was performed using repeated measures analysis of
variance. RESULTS: When subjects used diclofenac PLO, pain was significantly less
than that during the pretreatment, washout, and placebo PLO periods (mean VAS:
diclofenac PLO, 2.1; pretreatment, 3.5; washout, 3.4; placebo PLO, 3.6). Average
wrist extension strength was significantly greater when subjects used diclofenac
PLO (8.4 kg) than it was before treatment (5.9 kg). One subject developed a local
rash while using diclofenac PLO. CONCLUSION: Topical 2% diclofenac in PLO appears
to provide effective short-term reduction in elbow pain and wrist extensor
weakness associated with chronic lateral epicondylitis.
PMID- 9641434
TI - A randomized controlled trial of the effect of naproxen on delayed onset muscle
soreness and muscle strength.
AB - OBJECTIVE: To determine the effect of naproxen in attenuating the symptoms
(muscle soreness level) and signs (plasma creatine kinase [CK] activity and
muscular strength decrement) of delayed onset muscle soreness (DOMS) induced by
repeated bouts of eccentric exercise. DESIGN: The design was a randomized, double
blind, placebo-controlled, crossover trial with two testing phases of 8 days'
duration that were separated by a "washout" period of 7 days. SETTING: University
based sports science center. PARTICIPANTS: Twenty healthy male volunteers who
responded to a notice in the university's athletic complex. INTERVENTIONS:
Eccentric single-leg exercises were performed on days 1, 3, and 4 to induce DOMS
in the quadriceps muscles. Naproxen or placebo tablets (500 mg) were taken orally
twice per day beginning on day 2 and continuing until the end of the testing
phase. MAIN OUTCOME MEASURES: Perception of muscle soreness and knee extensor
torque were evaluated daily throughout each phase. Plasma CK levels were
evaluated on days 1, 3, 6, and 8 of each phase. RESULTS: After the eccentric
exercise, plasma CK levels were similarly elevated in both naproxen and placebo
conditions (F=1.42; p=0.25). After DOMS developed, naproxen reduced the
perception of soreness on day 3, when muscle soreness was highest (F=2.20;
p=0.04). After treatments with naproxen, peak quadriceps torque during leg
extension at 60 degrees/s was higher than that after treatment with the placebo
(F=4.77; p=0.04). There were no significant differences between the naproxen and
placebo conditions for leg extension at 180 degrees/s (F= 1.66; p=0.21) and 300
degrees/s (F=0.71; p=0.41). CONCLUSION: The data indicate that therapeutic doses
of naproxen do not prevent CK release into the plasma but decrease the perception
of muscle soreness and positively influence quadriceps peak torque.
PMID- 9641435
TI - Comparison of injuries in classic and skating Nordic ski techniques.
AB - OBJECTIVE: To compare types and anatomic distribution of injuries between cross
country skiers using the classic and skating ski techniques. DESIGN: Descriptive
self-administered survey. SUBJECTS: Midlevel competitors in the 1996 American
Birkebeiner cross-country ski marathon (55 km). DESCRIPTION OF SURVEY: A self
administered 21-item questionnaire regarding skiing-related injuries occurring
during training before the race or during the marathon. The respondent was asked
for information regarding any skiing-related injury or complaint that occurred
during training or while participating in the American Birkebeiner ski race. This
tool also collected information regarding training habits, equipment selection,
and skier demographics. Responses were coded on a Mark-Sense form and compiled by
a computerized code reader. MAIN RESULTS: A total of 833 surveys were returned
for an overall response rate of 55%. The overall self-reported injury rate for
the surveyed group was 234 per 1000 skiers (i.e., 23.4% of skiers sustained an
injury during the race). Most of these injuries were minor; only 4.6% of all
skiers reported lost training time because of a race injury, and only 2.8% of all
skiers sought treatment from a health care provider for a race-related injury.
There was no statistically significant difference between the two techniques
either in overall injury rate (p=0.33) or in the location of the injury
(p=0.158). The injury rates were 23% and 27%, respectively, for skating and
classical techniques. The incidence of more serious injuries (those requiring
medical attention) was 2.7% for skaters and 3.1% for classical skiers. No
statistically significant relation was found between pole length and the
development of injuries. In addition, the likelihood of sustaining an injury was
independent of age and training distance. CONCLUSIONS: The overall injury rates
in this study were much higher than those previously reported in the literature,
but no significant difference in injuries between the two skiing techniques was
found. The incidence of more severe injuries, defined as those requiring medical
treatment, was consistent with previous reports. Prior assumptions regarding
equipment relationships to injuries were not substantiated by the findings. In
spite of significant changes in the equipment and technique designed to enhance
speed, cross-country skiing remains a safe sport, with its participants
relatively free of serious injuries. Further investigation is required to
determine whether other aspects of the sport, such as pole grip design, ski
construction, and skier skill level, have any relation to injury patterns.
PMID- 9641436
TI - Cervical spine alignment in immobilized hockey players: radiographic analysis
with and without helmets and shoulder pads.
AB - OBJECTIVE: To establish the appropriate technique for cervical immobilization of
the hockey player with an acute neck injury, we analyzed the alignment of the
cervical spine in healthy volunteers with combinations of applied hockey
equipment and assessed the amount of cervical spine motion possible in a secured
hockey helmet. Our hypothesis was that there is a significant difference among
various positions of the cervical spine with and without equipment and with
active motion in a secured helmet. DESIGN: We analyzed lateral cervical spine
radiographs of eight healthy male volunteers immobilized on a backboard with the
following combinations of hockey equipment: shoulder pads and helmet, shoulder
pads only, helmet only, no equipment, and neck flexion and extension with helmet
and shoulder pads on and helmet secured to the backboard. SETTING: Large
university hospital, tertiary care center. RESULTS: Cervical lordosis without
equipment (control) was not significantly different than cervical lordosis with
shoulder pads and helmet applied (p=0.31). Subjects with shoulder pads averaged
8.9 degrees more lordosis than did controls (p= 0.0002) and 6.6 degrees more
lordosis than did subjects with shoulder pads and helmets (p=0.027). Subjects
with shoulder pads and a helmet secured to the backboard were able to flex and
extend the cervical spine 12.9 degrees compared with the control position (p
=0.009). CONCLUSIONS: In an acute cervical spine injury involving an ice hockey
player, we recommend immobilization in both the helmet and the shoulder pads,
with removal of both pieces of equipment in a controlled hospital setting and
only after initial radiographic examination. We also recommend securing the
player's chin to prevent as much head and neck motion as possible during
transport and transfers.
PMID- 9641437
TI - The effects of muscular fatigue on shoulder proprioception.
AB - OBJECTIVE: To assess the influence of muscular fatigue on active and passive
shoulder proprioception within the midrange of rotation. DESIGN: A randomized
controlled, before-and-after design. SETTING: Neuromuscular research laboratory.
PARTICIPANTS: Twenty recreationally active men (mean age, 23.81+/-2.77 years)
were randomly assigned to either a control or a fatigue group. Exclusion criteria
were any history of upper extremity injury or pathology, cardiovascular disease,
or disease affecting the sensory system. INTERVENTION: Shoulder proprioception
was assessed by active reproduction of passive positioning (ARPP), active
reproduction of active positioning (ARAP), reproduction of passive positioning
(RPP), and threshold to detect passive motion (TTDPM). For each test direction,
the experimental group performed two bouts of maximal reciprocal concentric
isokinetic internal and external contractions at 180 degrees/s until peak torque
decreased to 50% of the established maximum voluntary contraction. After two
bouts of the fatigue protocol, subjects were randomly assessed for proprioception
into internal or external rotation. MAIN OUTCOME MEASURES: The absolute angular
error for active and passive proprioception was measured on the Biodex System II
Isokinetic Dynamometer (Biodex Medical Inc., Shirley, NY, U.S.A.) and a
proprioception testing device, respectively. MAIN RESULTS: A two-factor repeated
measures analysis of variance revealed no significant interactions between the
experimental and control groups for ARPP, ARAP, RPP, or TTDPM. CONCLUSIONS:
Shoulder proprioception was not affected by the short-duration, high-intensity
protocol used in this study. This may be due to the lack of an extended recovery
period observed with this type of fatigue regimen.
PMID- 9641438
TI - The fate of meniscal tears after anterior cruciate ligament reconstruction.
AB - OBJECTIVE: To investigate the incidence of meniscal pathology and subsequent
treatment at an index arthroscopically assisted reconstruction of acute ACL tears
(<3 weeks after injury) and to determine the outcome of meniscal pathology.
DESIGN: Cohort study with average postoperative follow-up of 40 months (range, 24
76 months). SETTING: University-based sports medicine center. PATIENTS: Series of
162 patients admitted between January 1989 and July 1993. Follow-up was obtained
for 105 patients. MAIN OUTCOME MEASURES: Initial presence, location, and
treatment of meniscal tears. Subsequent surgery performed and further
investigation or surgery being planned. RESULTS: Approximately 40% of patients
had meniscal pathology at the index procedure. Most tears were in the lateral
meniscus (34 of 45). All posterolateral tears and most other small tears were
left untreated (25 of 45). Partial meniscectomies were performed on 17 large,
complex, or radial tears that were not amenable to meniscal resuturing. Three
meniscal repairs were performed on large, unstable tears. Most patients achieved
good functional results. Of the five patients who required late meniscal surgery,
three had normal menisci at the index procedure. The other two were asymptomatic
until experiencing a reinjury. Despite ACL reconstruction in the acute phase,
only two patients required treatment for postoperative arthrofibrosis. Three
patients required revision ACL reconstruction after return to full activities and
experiencing reinjuries. CONCLUSIONS: Stable tears of both lateral and medial
menisci remain asymptomatic at 2 to 6 years' follow-up if treated conservatively.
Those requiring further surgery had de novo tears or tears that were asymptomatic
before reinjury. Although repair may be of benefit for large flap or bucket
handle tears, it does not appear necessary for most tears and may increase the
incidence of postoperative stiffness.
PMID- 9641439
TI - Repetitive activity alters perfusion of proximal interphalangeal joints of the
human hand.
AB - OBJECTIVE: To examine whether competitive volleyball players show any difference
in perfusion of their proximal interphalangeal (PIP) joints compared with a
healthy group of subjects. Also to assess the viability of a dual wavelength
laser Doppler imager (LDI) in making these measurements. SETTING: Physiology
laboratory. PARTICIPANTS: Ten active volleyball players who had experienced
repetitive finger joint injury and 12 age- and sex-matched normal control
subjects. MAIN OUTCOME MEASURES: Using a modified LDI incorporating a near-
infrared (850 nm) laser as well as a standard red (633 nm) laser, scans were
performed over the dorsum of the hands of the volleyball players and the control
group. RESULTS: Higher perfusion values were obtained with the 850-nm laser than
with the red 633-nm laser. When referenced to adjacent skin blood flow, perfusion
over PIP joints of volleyball players was found to be significantly higher than
that in control subjects (p=0.00012; n=10-12). CONCLUSIONS: The higher perfusion
values obtained using the 850-nm laser suggest that the longer wavelength laser
is measuring perfusion in a greater volume of tissue, which could include
subcutaneous structures. Volleyball players have significantly higher perfusion
over the PIP joints, which is unlikely to be due to differences in skin perfusion
over the two regions but is more likely to be related to hyperemia of the
underlying PIP joints. The reason for increased PIP perfusion is not clear; it
may represent ongoing tissue inflammation due to repeated injury, or it could be
an adaptive response to the stresses placed on these joints by this type of
repetitive activity. CLINICAL RELEVANCE: Near-infrared laser Doppler imaging has
the potential to provide a noninvasive clinical assessment of finger joint
injuries.
PMID- 9641440
TI - In-line skating: use of protective equipment, falling patterns, and injuries.
AB - OBJECTIVE: To determine the use of protective equipment, reasons for nonuse of
protective equipment, and patterns of injury, falls, and stopping techniques of
recreational in-line skaters. DESIGN: Survey. PARTICIPANTS: 313 in-line
recreational skaters observed skating in the parks, on bicycle trails, and on
parkways in Milwaukee, Wisconsin and Columbus, Ohio were asked to participate in
a short survey in 1995. MAIN OUTCOME MEASUREMENTS: The frequency of in-line
skater use of protective equipment, reasons for nonuse, patterns of injury, and
patterns of falls. RESULTS: Protective equipment was worn most of the time in the
following proportions of skaters [95% confidence interval in brackets]: wrist
guards (51%) [44.7%-58.1%]; knee pads (36%) [29.3%-42.5%]; elbow pads (15%) [8.4%
22.8%]; and helmets (15%) [8.0%-22.0%]. Reasons cited for not using protective
equipment included lack of perceived need (47.3%), discomfort (37.5%), cost
(15.9%), and undesirable appearance (15.2%). Stopping techniques included skating
off into the grass (14.6%) [11.8%-17.4%] and voluntarily falling (3.5%) [2.1%
4.9%]. Causes of involuntary falls included spontaneous loss of balance (32.9%)
[28.9%-36.9%], hitting rocks or other small objects (17.3%) [14.4%-20.2%], uneven
pavement (17%) [14.2%-19.8%], and failure to stop (11.3%) [8.4%-14.2%]. Site of
initial impact after falling included the hands and wrists (44.6%) [38.3%-50.9%],
the knees (19.6%) [16.4%-22.8%], and the buttocks region (17.2%) [14.3%-20.1%].
Injuries had occurred in 26% of the skaters; 14% of injuries were fractures.
CONCLUSIONS: In-line skaters often do not wear protective equipment because they
believe it is not necessary. Recent studies have suggested, however, that
protective equipment does prevent injuries. Physicians should counsel their
patients who are in-line skaters to use protective equipment.
PMID- 9641441
TI - Body fatness and increased injury rates in high school football linemen.
AB - OBJECTIVE: To determine whether associations exist between body fatness and
injury rates in high school football linemen. DESIGN: Prospective, injury
surveillance study during a 2-week preseason and 10-week regular season. SETTING:
10 public high schools in Texas. PARTICIPANTS: Two hundred fifteen varsity and
junior varsity high school football linemen. MAIN OUTCOME MEASURES: Injury rates
(injuries per 1000 hours of playing time) for groups of players above a given
body fat level and at or below a given body fat level. Rates were computed as the
number of injuries per group divided by the group's aggregate playing time
(practice + game time). The null hypothesis was that there is no difference in
injury rates between players above a given level of body fat and those at or
below that level of body fat. Body fat was determined from chest, abdomen, and
thigh skinfold measurements using standard conversion equations. Body mass index
(BMI) (kg/m2) was also calculated for each player. RESULTS: The overall injury
rate was 5.66 injuries per 1000 hours of playing time. Percent body fat ranged
from 9.3% to 40.2%. BMI ranged from 19.9 to 46.6 kg/m2. Sixty-seven players
sustained 86 injuries, the most common of which were ankle sprains and medial
collateral ligament sprains. No difference in overall injury rates between higher
and lower fat groups was seen at any body fat level. Players in higher body fat
groups, however, had significantly greater lower extremity injury rates than did
players in lower fat groups between 18% and 27% body fat and again 32% to 33%,
but not at intermediate levels or >33%. Players in higher BMI groups had
significantly greater lower extremity injury rates than did players in lower BMI
groups throughout the range from 24 to 36 kg/m2, except at 34 kg/m2. CONCLUSION:
Both higher body fatness and BMI were associated with increased rates of lower
extremity injury among high school football linemen. BMI appears to be associated
more consistently with increased lower extremity injury rates than is body fat.
PMID- 9641442
TI - A clinical test for superior glenoid labral or 'SLAP' lesions.
AB - OBJECTIVE: To describe a clinical test associated with unstable lesions of the
superior glenoid labrum-long head biceps tendon origin, or SLAP (superior labrum
anterior to posterior). DESIGN: Description of a newly discovered clinical sign
that correlated with SLAP pathology. Retrospective review of 66 consecutive
arthroscopically confirmed SLAP lesions to determine the sensitivity of the
SLAPprehension test. SETTING: Orthopedic sports medicine clinics with an emphasis
on shoulder problems. PATIENTS: Patients with shoulder pain and arthroscopically
verified lesions of the superior glenoid labrum and conjoined long head biceps
tendon. INTERVENTION: Shoulder arthroscopy and in some cases arthroscopic SLAP
lesion repair. OUTCOME MEASURES: Nonapplicable. RESULTS: The SLAPprehension test
involves cross chest adduction (horizontal flexion) of the affected shoulder with
the elbow extended and forearm pronated. A positive maneuver produces either
apprehension, pain referable to the bicipital groove, and an audible or palpable
click. The test is repeated with the forearm supinated, which must cause
diminution of the pain. Mechanically, elbow extension and forearm pronation
places traction on the long head biceps tendon. When anterior scapular
protraction is limited by the clavicle, further adduction entraps the unstable
biceps tendon and superior glenoid labrum between the glenoid fossa and humeral
head. Forearm supination decreases traction on the long head biceps tendon and
allows for reduction of the unstable labrum complex with lessening of the pain. A
retrospective chart review of 66 consecutive arthroscopically verified shoulders
with SLAP lesions revealed the SLAPprehension test to be 87.5% sensitive for
unstable SLAP lesions. CONCLUSIONS: The SLAPprehension test is helpful in the
clinical evaluation of patients with unstable superior glenoid labrum lesions
whose symptoms are often confused and overlap with those of shoulder impingement
or acromioclavicular arthrosis.
PMID- 9641443
TI - On-field management of potential cervical spine injury in helmeted football
players: leave the helmet on!
AB - OBJECTIVE: Improper handling of an unstable neck injury in the prehospital
setting may result in potential iatrogenically induced neurologic injury. On-site
management of the neck-injured, helmeted football player differs from that of
other traumatic cervical spine injuries. Controversy still exists regarding
helmet removal protocols for stabilizing the cervical spine of helmeted football
players with a suspected neck injury. This article provides a critical review of
the scientific evidence on cervical spine management in helmeted football players
with a suspected cervical spine injury. DATA SOURCES: A computerized literature
search of databases (MEDLINE, Sportdiscus) and a manual search of journals from
the sports medicine, emergency medicine, orthopedic, and athletic training
literature identified articles related to the topic. Additional references were
reviewed from the bibliographies of the retrieved articles. STUDY SELECTION:
Conclusions are based on five quasi-experimental study designs evaluating
motorcycle, football, and hockey helmet removal. In addition, an attempt was made
to correlate articles relating to airway and cervical spine management in general
trauma to the helmeted athlete. MAIN RESULTS: Several studies support the
recommendation not to remove the helmet or shoulder pads in the prehospital
setting unless absolutely necessary. If necessary, both helmet and shoulder pads
should be removed together as a unit. There are neither published studies in
support of helmet removal nor any case reports of increased morbidity to athletes
because of failure to remove the helmet in the prehospital setting. CONCLUSIONS:
Although studies support the notion that iatrogenic neurologic deterioration may
occur with improper handling and attempted removal of the helmet in the
prehospital setting, there is no literature to support increased morbidity
associated with not removing helmet and shoulder pads. Stabilization of the
cervical spine in an injured football player does not require routine prehospital
removal of the helmet and shoulder pads before transport.
PMID- 9641444
TI - The traveling athlete: issues relating to the Commonwealth Games, Malaysia, 1998.
PMID- 9641445
TI - Osteonecrosis of the tarsal navicular in two adolescent soccer players.
PMID- 9641446
TI - Arthroscopic findings in luxatio erecta of the glenohumeral joint: case report
and review of the literature.
AB - PURPOSE: We report the case of an inferior glenohumeral dislocation of the
shoulder in which arthroscopic assessment showed an extensive detachment of the
labral-biceps tendon complex (Bankart and superior labrum anterior posterior
[SLAP] lesions). We sought to review the literature to compare our findings with
the reported lesions in this type of shoulder dislocation. CASE SUMMARY: A young
patient presented with an inferior dislocation of his right shoulder (erect
dislocation) after having sustained a motorcycle accident. Conventional
radiographs revealed the humeral shaft parallel to the scapular spine and an
anteroinferior position of the humeral head with a large avulsion of the greater
tuberosity. Preceding arthroscopy showed a complete detachment of the anterior
labrum and ligament complex (SLAP lesion). After open reduction and internal
fixation of the greater tuberosity, the capsulolabral complex was reduced and
securely fixed with three bone anchors at the glenoidal rim. The patient
recovered well reaching full shoulder function after 5 months and regaining the
former sports activity level within 9 months after surgery. DISCUSSION:
Arthroscopy identified the location and extent of an important labral detachment
that, in combination with the stability testing under anesthesia, proved the need
for a labral refixation. The literature regarding reported pathology in inferior
glenohumeral dislocation is reviewed, and the additional information on
associated soft-tissue lesions by means of arthroscopy are discussed. RELEVANCE:
No prior case of arthroscopic assessment in inferior glenohumeral dislocation of
the shoulder has been reported. Recognizing the extent and site of accompanying
labral detachments contributing to the instability of the joint may enhance our
knowledge of the full pathology in these dislocations and thus allow an adequate
surgical treatment.
PMID- 9641447
TI - Compliance with exercise therapy in treating seniors with knee osteoarthritis.
PMID- 9641448
TI - Clinical relevance of serial sectioning of sentinel nodes and the detection of
micrometastatic nodal disease in breast cancer.
PMID- 9641449
TI - Addressing the axilla in breast cancer, 1998.
PMID- 9641450
TI - The John Wayne Clinical Research Lecture. Surgical management of melanoma:
results of prospective randomized trials.
PMID- 9641451
TI - Serial sectioning of sentinel nodes in patients with breast cancer: a pilot
study.
AB - BACKGROUND: Recent reports indicate that the sentinel node, defined as the first
regional lymph node to receive lymphatic fluid from the breast, accurately
represents the metastatic status of the primary breast cancer. However, routine
single section examination of the regional nodes, including the sentinel node,
underestimates the true incidence of metastases. The goal of this study is to
determine whether multiple sectioning of sentinel nodes will detect occult
metastases in operable breast cancer. METHODS: Nineteen patients with invasive
breast cancers were injected with technetium-99m sulfur colloid solution around
the tumor or at the biopsy site before lumpectomy and axillary lymph node
dissection (ALND) or mastectomy. The labeled sentinel lymph nodes (SLND) were
bivalved, and a central section was taken for hematoxylin and eosin (H & E)
examination. The sentinel nodes of 13 patients, which were reported to be
negative for metastases, were serially sectioned at 0.5-mm intervals and stained
with H & E and a cytokeratin stain, CAM 5.2. RESULTS: In the 13 node-negative
patients, occult metastases were found in the sentinel nodes of 3 patients (23%).
Two were seen on H & E and one by cytokeratin stain. The mean numbers of SLND and
ALND in this series were 2.6 and 12.5, respectively, and the average number of
sections for the two groups was 14 and 1, respectively. CONCLUSION: Multiple
sectioning of the sentinel node or nodes detects occult metastases and changes
the staging of breast cancer.
PMID- 9641452
TI - Ultrasonographically guided injection improves localization of the radiolabeled
sentinel lymph node in breast cancer.
AB - BACKGROUND: Several reports have demonstrated the accurate prediction of axillary
nodal status (ANS) with radiolocalization and selective resection of sentinel
lymph nodes (SLN) in breast cancer. To date, no technique has proven to be
superior in localizing the SLN. METHODS: 1.0 mCi of clear unfiltered
99mtechnetium sulfur colloid was injected under ultrasonographic (US) guidance
around the perimeter of the breast lesion (palpable and nonpalpable) or previous
biopsy site. Resection of the radiolocalized nodes was performed, followed by
complete axillary lymph node dissection (AXLND). RESULTS: Forty-two breast cancer
patients underwent SLN biopsy after US-guided radiopharmaceutical injection. The
SLN was localized in 41 patients (98%). The type of previously performed
diagnostic biopsy did not influence the ability to localize the sentinel lymph
node. Pathology revealed nodal metastasis in 7 of the 41 evaluable patients
(17%). ANS was accurately predicted in 40 of 41 patients (98%). CONCLUSIONS:
Early experience with radiolocalization and selective resection of SLN in breast
cancer remains promising. Use of US-guided injection facilitates localization of
the SLN, perhaps as a result of more accurate placement of the radionuclide
marker. Use of this technique allowed for effective management of patients
regardless of tumor size or the extent of prior biopsy, thereby expanding the
potential number of eligible patients for SLN biopsy.
PMID- 9641453
TI - Surgical margins and prognostic factors in patients with thick (>4mm) primary
melanoma.
AB - BACKGROUND: Randomized trials have demonstrated the efficacy of 1- and 2-cm
excision margins for thin and intermediate-thickness melanomas, respectively. The
optimal margin of excision for thick melanomas is still unknown, however. We
evaluated whether the margins used for intermediate-thickness melanomas can be
applied safely to thicker lesions. METHODS: The charts of 278 patients with thick
primary melanomas treated between 1985 and 1996 were retrospectively reviewed.
Patients with distant metastases at presentation or with follow-up less than 6
months were excluded. Median follow-up was 27 months. Known melanoma prognostic
factors and excision margins were evaluated for their impact on local recurrence
(LR), disease-free survival (DFS), and overall survival (OS). RESULTS: Median
tumor thickness was 6.0 mm, and 57% were ulcerated. At presentation, 201 patients
(72%) were node negative and 77 (28%) were node positive (palpable or occult).
The 5-year OS and DFS rates were 55% and 30%, respectively. The LR rate for all
patients was 12%. Although nodal status, thickness, and ulceration were
significantly associated with OS by multivariate analysis, neither LR nor
excisional margin (<2 cm vs. >2 cm) significantly affected DFS or OS in these
patients. CONCLUSIONS: Because margins of excision greater than 2 cm do not
improve LR, DFS, or OS compared to a margin of 2 cm or less, a 2-cm margin of
excision is adequate for patients with thick melanoma. Because nodal status is a
significant prognostic factor in these patients, staging by sentinel node biopsy
should be considered in patients with thick melanomas and clinically negative
nodal basins to allow proper entry and stratification in adjuvant therapy trials.
PMID- 9641454
TI - Localized well-differentiated thyroid carcinoma: survival analysis of prognostic
factors and (131)I therapy.
AB - BACKGROUND: Recommendations regarding therapeutic use of (131)I for patients with
well-differentiated thyroid cancer remain controversial. Between 1969 and 1993,
1171 patients with papillary (including mixed) or follicular thyroid cancer were
reported to the New Mexico Tumor Registry. Of these, 1075 cases (77.6% female,
median age 41 years) were available for analysis of survival plots and previously
recognized risk factors. Extent of operation was documented for 344 patients.
METHODS: One hundred twenty-seven (37%) patients underwent postoperative (131)I
ablation. Median follow-up was 99 months. A proportional hazards model was
constructed using age, gender, stage, histology, and use of radioiodine. The same
variables plus extent of operation were examined in the smaller group. RESULTS:
Kaplan-Meier survival estimates at 12 years were 96.2% for patients younger than
45 years and 68.6% for those older than 45 years. Age, gender, and histology, but
not stage, were important survival variables (P <.05). Adjusting for other risk
factors, there was no apparent survival benefit associated with radioiodine
following clinically appropriate thyroidectomy. Findings from the small group
mirrored those of the large group. CONCLUSIONS: (131)I may not be as efficacious
as previously believed for patients with well-differentiated thyroid cancer
confined to the neck.
PMID- 9641455
TI - Limited surgery for early gastric cancer in cardia.
AB - BACKGROUND: Because there are some difficulties with the diagnosis of invasion or
the endoscopic resection technique, almost all gastric tumors are resected
surgically. Surgeons now are performing a limited operation for early gastric
cancer of the upper stomach (EGCUS) without lymph node metastasis. This paper
discusses and evaluates the surgical technique and the results of the limited
operation for EGCUS. PATIENTS AND METHODS: Since 1988, a total of 34 patients
with EGCUS, diagnosed as intramucosal invasion, have undergone a limited
operation--fundectomy--which includes a limited proximal gastrectomy, a limited
lymph node dissection, and a procedure preserving the vagal nerve. The surgical
risk, postoperative complications, and survival rates of the fundectomy patients
(group A) were compared with those of patients undergoing a total gastrectomy for
EGCUS (group B). RESULTS: Blood loss was lower in group A (300+/-193 mL) than in
group B (555+/-316 mL) (P <.05). The incidence of postoperative pancreatic
fistula also was lower in group A (0%) than in group B (15.0%) (P <.05). All
patients in both groups (except one who died of a cerebral infarction) are alive
without recurrence. CONCLUSION: Compared to the results of a total gastrectomy,
performance of a limited fundectomy for EGCUS decreased surgical risk and
postoperative complications without decreasing the survival rate.
PMID- 9641457
TI - Hemangiopericytoma: a 20-year single-institution experience.
AB - BACKGROUND: Hemangiopericytoma is an uncommon soft tissue sarcoma. We sought to
evaluate the long-term outcome of a consecutively treated patient cohort with
hemangiopericytoma. METHODS: The study involved 36 adult patients (older than 16
years) with hemangiopericytoma treated at The University of Texas M. D. Anderson
Cancer Center between July 1975 and July 1995. Data on clinicopathologic
parameters, surgical treatment, adjuvant therapy, disease recurrence, and
survival were obtained from a review of medical records. RESULTS: The median
follow-up was 57 months. Twenty-eight patients (78%) underwent complete and
potentially curative resection of their primary disease. Of the nine patients
(32%) who had local recurrences, four (57%) had epidural tumors and three (43%)
had retroperitoneal tumors, but none had extremity tumors. Extremity tumors were
associated with a significantly prolonged local recurrence-free survival compared
to tumors at nonextremity anatomic sites (P <.05). Ten patients had recurrences
at distant sites. Of the 13 patients who experienced any form of disease
recurrence, four had recurrences after a disease-free interval of more than 5
years. The 5-year actuarial survival rate for the entire group of 36 patients was
71%. Noncurative surgical treatment (P=.007) and development of distant
metastatic disease (P=.013) were associated with shortened survival. CONCLUSION:
Extended survival is common in hemangiopericytoma patients treated with curative
intent. However, local and distant recurrences may occur after a prolonged
disease-free interval, emphasizing the need for long-term follow-up.
Retroperitoneal and meningeal tumors were associated with higher local recurrence
rates; therefore, adjuvant therapies should be considered and evaluated for
tumors at these sites.
PMID- 9641456
TI - Cell cycle regulation of human pancreatic cancer by tamoxifen.
AB - BACKGROUND: Clinical trials have suggested a survival advantage for selected
patients with metastatic pancreatic cancer treated with tamoxifen. We sought to
identify the molecular mechanism by which tamoxifen inhibits human pancreatic
cancer cell (HPCC) growth. METHODS: HPCCs were grown in tamoxifen and growth
inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in
cell viability were determined by cell counts. Cell cycle alterations were
evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL
assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern
blot analysis was performed for p21waf1. RESULTS: Tamoxifen inhibited HPCC growth
as measured by inhibition of 3H-thymidine incorporation and by the MTT assay.
However, there was no decrease in the total number of viable cells after 6 days
of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the
absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in
the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to
tamoxifen treatment. CONCLUSIONS: Tamoxifen inhibits HPCC growth by inducing
G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is
an effective inhibitor of HPCC growth in vitro and warrants further in vivo
study.
PMID- 9641458
TI - Microsatellite instability in sarcomas.
AB - BACKGROUND: Microsatellite instability (MIN) has been studied in a variety of
carcinomas and gynecologic sarcomas, but never in musculoskeletal sarcomas.
METHODS: We evaluated 16 skeletal and soft tissue sarcomas at nine genetic loci
from chromosomal regions 1q, 5q, 7q, 12p, 13q, 17p, 19q, and two at 11p--all
potential regions of interest regarding musculoskeletal sarcomas. RESULTS: MIN
was identified at one or more loci in seven of the cancers studied (44%). Three
tumors had more than one locus with MIN and one tumor, a high-grade osteogenic
sarcoma, had five of nine loci positive for MIN. CONCLUSION: These results
indicate that musculoskeletal sarcomas show instability in areas inside and
outside the loci of known oncogenes. Areas of mismatch repair, as heralded by
MIN, may contribute to the vast heterogeneity of these neoplasms.
PMID- 9641459
TI - Tamoxifen alters levels of serum insulin-like growth factors and binding proteins
in postmenopausal breast cancer patients: a prospective paired cohort study.
AB - BACKGROUND: Recent data suggest that tamoxifen may act by altering serum levels
of insulin-like growth factors (IGFs) and their binding proteins (BPs). This
prospective paired cohort study evaluated the influence of tamoxifen on serum
levels of IGFs and BPs in postmenopausal patients with breast cancer. METHODS:
Blood was collected from 32 postmenopausal patients with breast cancer before and
during tamoxifen therapy for at least 6 months. All patients had undergone
primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were
determined by immunoradiometric assays, and Western ligand blots provided a
semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was
performed by paired Student's t-test. RESULTS: Mean serum IGF-1 level was
significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL+/-13.6
[SEM] vs. posttreatment: 77.5 ng/mL+/-7.8; P=.003). In contrast, mean IGF-II
levels increased from 651.5+/-62.2 ng/mL to 812.5+/-35.1 ng/mL during treatment
(P=.006). Posttreatment levels of BP-1 (92.9 ng/mL+/-7.5) were significantly
higher compared to the pretreatment values (28.1 ng/mL+/-4.7; P <.001). Serum
concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL+/-145.2 vs.
posttreatment: 3539.1 ng/mL+/-172.3; P <.001). Densitometric measurements showed
a similar significant increase in BP-3 (P <.001) as well as BP-4 (P=.017) after
hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment.
CONCLUSIONS: These significant alterations in serum concentrations of IGFs and
BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism
by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.
PMID- 9641460
TI - Competing causes of death for primary breast cancer.
AB - BACKGROUND: A patient's likelihood of dying from breast cancer or another cause
can be assessed with competing risks analyses. METHODS: Data for a cohort of 678
patients with primary invasive breast cancer accrued from 1971 to 1990, updated
to 1995, included cause of death (e.g., breast cancer vs. other cause). We
investigated the effects of age, tumor size, nodal status, ER, PgR, and adjuvant
therapy (hormones, chemotherapy, radiotherapy) on type of death and time to death
for patients of all ages and for those over the age of 65 years. RESULTS:
Although there were no significant univariate differences in breast cancer death
rates by age group (P=0.94), more patients over the age of 65 years died from
other causes (41/207 [20%] of those older than 65 years vs. 16/471 [3%] of those
younger than 65 years; P <.001). In competing risks analyses, older age was
associated with non-breast cancer death, whereas larger tumor size was associated
with breast cancer death. PgR was positively, and nodal status negatively,
associated with survival, regardless of type. In the older patient group, the
competing risks analyses identified similar effects for age and tumor size; in
addition, higher ER assay values were less likely to be associated with breast
cancer death. CONCLUSIONS: With increased lifespan, there will be more breast
cancer cases in women older than 65 years; we have shown that women in this group
have more non-breast cancer deaths. It becomes important, then, to delineate
differential effects of prognostic factors on competing causes of death.
PMID- 9641461
TI - Efficacy of hyperthermic isolated limb perfusion for extremity-confined recurrent
melanoma.
AB - BACKGROUND: Recurrent melanoma of the extremity has been treated by local
excision, systemic chemotherapy, amputation, or a combination of these
approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb
preservation through isolation, allowing the administration of chemotherapy in
higher doses than is possible through systemic treatment. METHODS: An
experimental group of 59 HILP patients with melanoma recurrences of the extremity
was studied prospectively. A control group of 248 melanoma patients with similar
recurrences was excluded from HILP because their recurrences were in non
extremity locations. The experimental group underwent HILP and excision; the
control group had excision only. The experimental procedure consisted of vascular
isolation of the affected extremity and a 1-hour perfusion with melphalan.
Temperatures were maintained at 40 degrees C in the perfusion circuit. RESULTS:
The HILP patients had a lower rate of locoregional recurrence (P=.028) and
demonstrated increased survival (P=.026) compared to the control group. In
multivariate regression analysis, which included age, ulceration and thickness of
the primary, and the treatment variable of perfusion, age (P=.02) and perfusion
for the treatment of recurrence (P=.006) were significant predictors of survival.
CONCLUSIONS: HILP improves prognosis by sterilizing the treated extremity,
controlling locoregional disease, and perhaps preventing metastasis, thus having
a positive impact on overall survival.
PMID- 9641462
TI - Lymphatic drainage from the skin of the back to retroperitoneal and paravertebral
lymph nodes in melanoma patients.
AB - BACKGROUND: Preoperative lymphoscintigraphy (LS) with 99mTc antimony sulphide
colloid is now part of the routine management of patients with intermediate
thickness melanoma at the Sydney Melanoma Unit. Over a 13-year period, 1375
patients have been examined using LS, and we have observed many unusual lymphatic
drainage pathways, including direct drainage through the body wall to
retroperitoneal and paravertebral lymph nodes from the skin of the back. The aim
of this study was to determine the incidence of such drainage in the 542 patients
who had primary melanoma sites on the posterior trunk. METHODS: The
lymphoscintigrams performed on these patients were examined for the presence of
direct lymphatic drainage through the posterior body wall to sentinel nodes in
the retroperitoneal and paravertebral regions. RESULTS: Lymphatic drainage
directly through the body wall to such lymph nodes occurred in 14 of these 542
patients. CONCLUSIONS: Preoperative knowledge of the presence of this lymph
drainage pattern may influence surgical management, and follow-up investigations
in these patients can be tailored to ensure that the relevant areas are examined
with anatomic imaging or F18-FDG PET scans.
PMID- 9641463
TI - Comparative hypotensive actions of three nonpeptide kappa opioid agonists on
hippocampus of SHRs and normotensive WKY rats.
AB - Comparative centrally mediated hypotensive effects of three nonpeptide kappa
opioid agonist drugs (bremazocine, spiradoline, and U-50,488H) were evaluated in
chloralose-anesthetized male spontaneously hypertensive rats (SHRs) and in
normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. The drugs were
administered unilaterally into previously established active hypotensive sites in
the dorsal hippocampus at doses of 12, 24, and 48 nmol. Each drug produced dose
related decreases in mean arterial pressure, ranging from -5 to -40% of predrug
control values, with bremazocine being somewhat more effective than spiradoline,
which was in turn slightly more active than U-50,488H. The effects were only
marginally greater in SHRs than in normotensive controls. Each drug caused a
modest decrease in heart rate, but except for the highest dose of bremazocine,
the effects were not statistically significant. The onset of hypotension after
intrahippocampal injection of each agent was approximately 2 min and lasted
approximately 30 min with U-50,488H and spiradoline and >60 min with bremazocine.
The responses to all three drugs were completely blocked by prior injection of
the active hippocampal sites with nor-binaltorphimine (nor-BNI), a selective
kappa-receptor antagonist. Because bremazocine is more selective for kappa-2
opioid receptors, whereas U-50,488H and spiradoline favor the kappa-1 subtype,
the results suggest that drugs active on each of these subtypes should be
investigated as potential antihypertensives.
PMID- 9641464
TI - Antagonism of LPS and IFN-gamma induction of iNOS in human saphenous vein
endothelium by morphine and anandamide by nitric oxide inhibition of adenylate
cyclase.
AB - Nitric oxide (NO) production regulates vasodilation in many blood vessels.
Additionally, constitutive NO release is being associated with positive
biomedical phenomena, whereas inducible NO synthase (iNOS)-associated NO release
with detrimental consequences in regard to endothelial inflammatory activities.
As yet, an important link demonstrating why one is activated over the other is
not available. Previous studies have demonstrated that morphine and anandamide
effector processes are coupled to NO release in human endothelial cells (ECs).
This study now extends this observation in that these endogenous signaling
molecules may use NO directly to inhibit adenylate cyclase activity. Activation
of human ECs, obtained from the saphenous vein, with morphine- or anandamide
stimulated NO release (35 nM and 28 nM, respectively) that peaked within 5 min
and returned to basal levels within 10 min of agonist stimulation, consistent
with constitutive NO synthase (cNOS) activation. Significant release of NO from
ECs stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)
occurred after 2 h after exposure and remained significantly increased over basal
levels for 24-48 h (28 nM), consistent with iNOS activation. Preincubation of ECs
with morphine or anandamide before, but not after, the addition of LPS + IFN,
blocked iNOS activity. Exposure of ECs to the NO donor, SNAP, before the addition
of LPS + IFN, blocked iNOS induction, whereas preincubation of ECs with
inhibitors of NOS, before morphine or anandamide exposure, restored LPS + IFN
induction of iNOS, suggesting a direct impact of NO on the regulation of iNOS
activity. Morphine and anandamide stimulation of ECs did not stimulate cyclic
adenosine monophosphate (cAMP) accumulation, whereas a marked increase in cAMP
was observed in ECs treated with LPS + IFN (8.2 to 33 pmol/mg protein). Treatment
of ECs with LPS + IFN did not induce cAMP accumulation in ECs treated with
morphine, anandamide, or SNAP before LPS + IFN exposure. These data suggest that
cAMP is required for the induction of iNOS in ECs and that NO may directly impair
adenylate cyclase activity, preventing iNOS activation.
PMID- 9641465
TI - Nitroglycerin fails to dilate coronary collateral vessels during exercise.
AB - This study was performed to determine whether nitroglycerin can increase blood
flow to collateral-dependent myocardium during exercise. Intermittent repetitive
occlusions of the left circumflex coronary artery (LCX) were used to stimulate
growth of coronary collateral vessels in seven adult mongrel dogs. Coronary
pressure distal to the occluder was measured with a long-term implanted
microcatheter. When sufficient collateral growth had occurred to increase distal
coronary pressure to >40 mm Hg during occlusion, the artery was permanently
occluded. Dogs were returned to the laboratory 1 week later for study.
Measurements were obtained at rest and during treadmill exercise during control
conditions and after a 300-microg bolus of nitroglycerin (i.v.). Aortic and
coronary pressures were measured with fluid-filled catheters, whereas myocardial
blood flow was measured with radioactive microspheres. During control conditions,
exercise caused significant increases of blood flow in the normal and collateral
zones with significant decreases in vascular resistance. However, nitroglycerin
failed to cause a further increase in blood flow to either the normal or the
collateral-dependent myocardial regions during exercise. Furthermore, neither
calculated transcollateral resistance (TCR) nor small-vessel resistance (SVR)
changed significantly in response to nitroglycerin (TCR, 27 +/- 9 mm Hg/ml/min/g
before nitroglycerin and 27 +/- 6 mm Hg/ml/min/g after; SVR, 43 +/- 5 mm
Hg/ml/min/g before nitroglycerin and 49 +/- 7 mm Hg/ml/min/g after). The finding
that the collateral vessels failed to dilate in response to nitroglycerin
suggests that the nitric oxide system is already maximally recruited during
exercise.
PMID- 9641466
TI - Comparison of in vitro cardiovascular function with in vivo echocardiographic
assessment after long-term administration of cyclosporine to rats.
AB - Clinical reports indicate that cyclosporine is able to induce heart failure
without rejection after heart transplantation. This supposition is supported by
ex vivo animal studies, yet ex vivo studies do not account for the potential of
counter-regulatory mechanisms, and the clinical observations seem rare in
comparison with the number of patients treated with cyclosporine. We hypothesized
that cyclosporine administration to rats would fail to exhibit any effect on
myocardial contractility in vivo notwithstanding a negative influence ex vivo.
Transthoracic echocardiographic examinations (two-dimensional targeted M-mode
tracings) were done in a blinded fashion before and after 1-week treatment of
rats (10 or 20 mg/kg/day cyclosporine i.p. vs. vehicle). After excision of the
hearts, contractility and changes in coronary tone were determined ex vivo during
flow-constant perfusion. Neither cyclosporine nor vehicle treatment resulted in
changes of echocardiographic parameters (left ventricular diameter, fractional
shortening). The heart rate was significantly increased in the high-dose
cyclosporine group. This group showed a significant 38% reduction of
contractility during the subsequent perfusion ex vivo, whereas low-dose
cyclosporine or vehicle had no effect on myocardial performance. Vasoconstriction
did not account for this impairment, because coronary tone was unaltered.
Cyclosporine, given in doses used in animal studies, impairs myocardial
contractility ex vivo but fails to exhibit any effect on myocardial performance
in vivo, possibly because of an increase in sympathetic tone. Considering that
the denervated transplanted heart in humans is even sensitized to adrenergic
stimuli, our finding makes unlikely a clinical contribution of cyclosporine to
failure after orthotopic heart transplantation.
PMID- 9641468
TI - Effect of the type IV phosphodiesterase inhibitor Ro 20-1724 on catecholamine
induced alterations in regional vascular resistance and regional blood flow.
AB - Type IV phosphodiesterase inhibitors have been studied in multiple disease
processes that commonly afflict patients who are treated with catecholamine
infusions. To examine whether type IV phosphodiesterases alter catecholamine
induced changes in systemic and regional hemodynamic parameters, we examined the
effects of Ro 20-1724 on rats during dobutamine, epinephrine, isoproterenol, and
norepinephrine infusions. Twenty-six Sprague-Dawley rats received either Ro 20
1724 or vehicle. After central and regional hemodynamic monitoring was initiated,
animals received increasing doses of two of the four catecholamines. In the
absence of catecholamines, Ro 20-1724 infusion caused a significant increase in
heart rate and a trend toward an increase in superior mesenteric artery blood
flow. Ro 20-1724 attenuated the increase in blood pressure caused by epinephrine
but had no effect on the dobutamine-, isoproterenol-, or norepinephrine-induced
changes in blood pressure. Ro 20-1724 had no effect on catecholamine-induced
changes in renal, carotid, and hindquarter vascular resistance but did attenuate
the decrease in superior mesenteric artery vascular resistance caused by
isoproterenol. Type IV phosphodiesterase inhibition in combination with
catecholamines has no adverse effects on regional hemodynamics; however, it can
inhibit the ability of epinephrine infusion to increase blood pressure.
PMID- 9641467
TI - Doxazosin inhibits proliferation and migration of human vascular smooth-muscle
cells independent of alpha1-adrenergic receptor antagonism.
AB - Proliferation and migration of vascular smooth-muscle cells (VSMCs), stimulated
by a variety of growth factors, play a critical role in the pathogenesis of
vascular diseases. We found unexpectedly that doxazosin, an alpha1-adrenergic
receptor antagonist, inhibits serum-stimulated proliferation of cultured human
VSMCs. Subsequent experiments systematically investigated inhibitory effects of
doxazosin on mitogenesis stimulated in VSMCs by platelet-derived growth factor
(PDGF), epidermal growth factor, and G protein-coupled receptor agonists thrombin
and angiotensin II. Doxazosin attenuated the stimulation of DNA synthesis for
each of these ligands with median inhibitory concentrations (IC50s) from 0.3 to 1
microM. PDGF-AB (1 nM) increased cell number; doxazosin inhibited this response
by 70-80%. Prazosin, a related alpha1-receptor antagonist, had similar but less
potent effects on inhibiting mitogenesis in these cells. Doxazosin and prazosin
inhibited PDGF-AB-stimulated and insulin-like growth factor (IGF-I)-stimulated
migration of VSMCs by approximately 40-50%. These effects of doxazosin were
likely unrelated to alpha1-receptor blockade because pretreatment of cells with
phenoxybenzamine, an irreversible alpha1 antagonist, did not change the capacity
of doxazosin to inhibit of PDGF-stimulated mitogenesis. Also, doxazosin inhibited
PDGF-stimulated DNA synthesis in NIH 3T3 cells, which do not express alpha1
receptors. These results suggest that doxazosin is a potent inhibitor of VSMC
proliferation and migration through a mechanism unrelated to alpha1-receptor
antagonism.
PMID- 9641469
TI - Renal vascular responses to angiotensin II in conscious spontaneously
hypertensive and normotensive rats.
AB - It has been postulated that exaggerated renal sensitivity to angiotensin II may
be involved in the development and maintenance of hypertension in the
spontaneously hypertensive rat (SHR). The purpose of this study was to compare
the renal vascular responses to short-term angiotensin II infusions (50
ng/kg/min, i.v.) in conscious SHRs and Wistar-Kyoto (WKY) rats. Renal cortical
blood flow was measured in conscious rats by using quantitative renal perfusion
imaging by magnetic resonance, and blood pressure was measured by an indwelling
carotid catheter attached to a digital blood pressure analyzer. Renal vascular
responses to angiotensin II were similar in control SHRs and WKY rats.
Pretreatment with captopril to block endogenous production of angiotensin II
significantly augmented the renal vascular response to exogenous angiotensin II
in the SHRs but not in the WKY rats. The renal vascular responses to angiotensin
II were significantly greater in captopril-pretreated SHRs than in WKY rats
(cortical blood flow decreased by 1.66 +/- 0.13 ml/min/g cortex in WKY rats
compared with 2.15 +/- 0.14 ml/min/g cortex in SHR; cortical vascular resistance
increased by 10.5 +/- 1.4 mm Hg/ml/min/g cortex in WKY rats compared with 15.6 +/
1.7 mm Hg/ml/min/g cortex in SHRs). Responses to angiotensin II were completely
blocked in both strains by pretreatment with the angiotensin II AT1-receptor
antagonist losartan. Results from this study in conscious rats confirm previous
findings in anesthetized rats that (a) the short-term pressor and renal vascular
responses to angiotensin II are mediated by the AT1 receptor in both SHRs and WKY
rats, and (b) the renal vascular responses to angiotensin II are enhanced in SHRs
compared with WKY rats when endogenous production of angiotensin II is inhibited
by captopril pretreatment.
PMID- 9641470
TI - Long-term exposure of human blood vessels to HIV gp120, morphine, and anandamide
increases endothelial adhesion of monocytes: uncoupling of nitric oxide release.
AB - Acute exposure of human saphenous vein or internal thoracic artery endothelium to
either morphine [27.4 +/- 3.7 and 35.4 +/- 4.1 nM nitric oxide (NO),
respectively] or anandamide (18.3 +/- 2.2 and 24.3 +/- 3.0 nM, respectively)
results in NO release, whereas exposure to the human immunodeficiency virus
envelope protein gp120 does not. After the short-term exposure of the vessel
endothelium, monocyte adherence is diminished with morphine and anandamide
treatment (jointly by -80%), whereas it is enhanced with that of gp120
(approximately 40%), indicating that gp120 enhances the ability of the
endothelium to adhere monocytes. Long-term or continuous exposure of the
endothelia to all agents results in a significant enhancement of monocyte
adherence (p < 0.05), which is further increased when exposed to either morphine
and anandamide plus gp120. This is caused by a desensitization of the endothelium
to further NO release after the initial exposure to either anandamide or
morphine. The results serve to indicate that in individuals abusing opiates and
or cannabinoids, a tissue [i.e., central nervous system (CNS)] viral load may be
higher, and acquired immunodeficiency syndrome (AIDS) may progress more rapidly
because monocyte adherence and mobility is significantly increased, indicating a
higher level of transmembrane migration.
PMID- 9641471
TI - Facilitation of reflex bradycardia does not contribute to the enhanced
hypotensive effect of clonidine in aortic barodenervated rats.
AB - Our previous studies showed that the hypotensive effect of clonidine is enhanced
in rats with surgically eliminated aortic baroafferents. In this study, we
investigated whether this effect of clonidine is related to facilitation of
baroreceptor control of reflex bradycardia. The effects of clonidine on blood
pressure (BP), heart rate (HR), and baroreflex-mediated decreases in HR
(baroreflex sensitivity, BRS) were studied in conscious aortic barodenervated
(ABD) and sham-operated (SO) rats. The slope of the baroreflex curve relating
increments in mean arterial pressure (MAP) induced by phenylephrine to
corresponding baroreflex-mediated bradycardic responses was taken as an index of
BRS. ABD but not the sham operation caused immediate and significant (p < 0.05)
increases in BP and HR and an impairment of BRS. Two days after ABD, these
parameters, except the BRS, subsided to near control levels. Starting from
similar baseline values of BP and HR, clonidine (30 microg/kg, i.v.) elicited
significantly (p < 0.05) greater decreases in MAP in conscious ABD rats compared
with SO rats (-23 +/- 2 mm Hg vs. -7 +/- 2 mm Hg). The enhanced hypotensive
effect of clonidine in ABD rats was associated with a significant reduction in
baroreceptor-mediated reflex bradycardic responses to increments in BP evoked by
phenylephrine. The slope of the baroreflex curves that represented the BRS showed
approximately 40% reduction after treatment with clonidine (baseline BRS, -1.2 +/
0.06 beats/min/mm Hg; clonidine, -0.73 +/- 0.07 beats/min/mm Hg). On the other
hand, a threefold lower decrease in BP by clonidine in SO rats was not associated
with any alteration in BRS. These findings support the hypothesis that aortic
baroreceptors exert a tonically active restraining influence on centrally
mediated hypotension. More important, the results do not favor a role for
facilitation of baroreflexes in the enhanced hypotensive effect of clonidine in
denervated rats.
PMID- 9641472
TI - Short-term myocardial uptake of d- and l-sotalol in humans: relation to
hemodynamic and electrophysiologic effects.
AB - The myocardial concentration of many cardioactive drugs has been identified as an
important determinant of their short-term effects in previous studies. Although
sotalol is frequently administered via short-term intravenous injection, no
previous studies had sought to correlate its uptake by the heart with its various
effects. We determined the time course of short-term uptake of d,l-sotalol by
human myocardium in vivo and investigated the relation between myocardial content
of sotalol and the short-term hemodynamic, electrocardiographic, and
electrophysiologic effects of the drug. Sixteen patients received a 20-mg
intravenous bolus of sotalol at the time of diagnostic cardiac catheterization.
Myocardial content of d- and l-sotalol (by using a paired transcoronary sampling
technique) and the short-term hemodynamic and electrophysiologic effects of the
drug were determined < or = 20 min after injection. Myocardial accumulation of
sotalol was not enantioselective, proceeded very rapidly (maximal at 0.74 +/-
0.10 min, representing 2.05 +/- 0.45% of the total injected dose), and was not
significantly influenced by left ventricular systolic function or the extent of
coronary artery disease. Approximately one third of peak myocardial content was
still present 17.5 min after sotalol administration. Maximal effects of the drug
(reduction in spontaneous heart rate, p < 0.005; reduction in maximal rate of LV
pressure increase (LV+dP/dtmax, p < 0.005); and prolongation of PR intervals, p <
0.02) were delayed by approximately 10 min relative to maximal myocardial sotalol
content. The significant prolongation of AH intervals (p < 0.01) and
atrioventricular nodal effective refractory periods (p < 0.0002) that was
observed was also maximal 10 min after administration of sotalol. Thus a
consistent delay between myocardial sotalol content and the short-term effects of
the drug was observed. In conclusion, the accumulation of both d- and l-sotalol
by the human myocardium is more rapid than that of any other agent studied to
date, with considerable hysteresis between myocardial drug uptake and subsequent
cardiac effects.
PMID- 9641473
TI - Relationship between myocardial milrinone content and its acute hemodynamic and
electrophysiologic effects.
AB - One of the major determinants of the short-term effects of many cardioactive
drugs is the concentration of the drug specifically within the myocardium.
However, no information regarding the disposition of the phosphodiesterase
inhibitor milrinone in the heart is available. We therefore determined the time
course of short-term myocardial milrinone uptake from paired transcoronary
sampling and simultaneous coronary sinus blood flow after a 1-mg intravenous
bolus in patients undergoing diagnostic cardiac catheterization. In accordance
with this intention, a sensitive, reproducible method for the determination of
milrinone in human whole-blood samples was developed. The reverse-phase high
performance liquid chromatographic method described used a C18 column with UV
absorbance detection at 326 nm, with a limit of detection of 0.6 ng/ml, and was
highly reproducible. The short-term hemodynamic and electrophysiologic effects of
the drug also were determined. Significant increases in spontaneous heart rate
and LV+dP/dtmax (at constant heart rate) were observed, accompanied by reductions
in mean arterial pressure, systemic vascular resistance, and PR interval, without
significant changes in atrioventricular nodal or ventricular effective refractory
periods. Peak content (1.89 +/- 0.30% of injected dose) was rapidly attained,
0.56 +/- 0.06 min after milrinone injection. Time of peak effects was
significantly delayed (7-10 min after injection) relative to time of peak
myocardial milrinone content. Residual myocardial milrinone content was 69.1 +/-
5.7% of maximum 12.5 min after injection. It is concluded that both myocardial
uptake and the onset of positive inotropic effects after intravenous injection of
milrinone were very rapid. However, there was significant hysteresis between peak
myocardial content and subsequent hemodynamic effects.
PMID- 9641474
TI - K-ATP-blocking diuretic PNU-37883A reduces plasma renin activity in dogs.
AB - We determined the effects of the K-adenosine triphosphate (ATP)-blocking diuretic
PNU-37883A on plasma renin activity (PRA) in conscious and anesthetized dogs. In
conscious dogs, oral PNU-37883A (6-60 mg/kg) was less potent than
hydrochlorothiazide (0.15-1.5 mg/kg) and furosemide (FURO; 0.3-3.0 mg/kg) but
exhibited high natriuretic efficacy with little kaliuresis. Unlike the standard
diuretics, PNU-37883A reduced PRA by 46-76%, and its high dose minimally affected
24-h urinary aldosterone excretion. PNU-37883A, 1 mg/kg i.v., also blunted the
hyperreninemia induced by 1 mg/kg i.v. FURO. In cannulated dogs, 10 mg/kg i.v.
PNU-37883A maximally increased fractional Na+ clearance 140% and reduced PRA 76%,
but these effects were accompanied by a mean 13 mm Hg pressor effect. In
anesthetized dogs, renal artery-infused PNU-37883A (3 mg/kg/h i.r.a.) increased
Na+ excretion and reduced renal venous PRA independent of hemodynamics, whereas
half this dosage selectively reduced renal venous PRA and renin release,
independent of hemodynamics and natriuresis. These data demonstrate that the K
ATP blocker diuretic PNU-37883A reduces PRA in dogs after oral, i.v., and i.r.a.
administration and could be a useful pharmacologic agent for exploring the role
of K-ATP channels in regulating renin release.
PMID- 9641475
TI - Changes in platelet function and susceptibility of lipoproteins to oxidation
associated with administration of aged garlic extract.
AB - Garlic and some of its organosulfur components have been found to be potent
inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in
vivo, however, especially when administered over extended periods, is sparse. We
recently performed a 10-month study comparing the effect of aged garlic extract
(AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men.
In the course of the intervention trial, we examined platelet functions and
susceptibility of lipoproteins to oxidation in a subgroup of this study
population. Study subjects supplemented with 7.2 AGE per day showed a significant
reduction of epinephrine- and, to a lesser degree, collagen-induced platelet
aggregation but failed to demonstrate an inhibition of adenosine diphosphate
(ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar
flow chamber at moderately high shear rate, was reduced by approximately 30% in
subjects taking AGE compared with placebo supplement. A trend toward decreased
susceptibility of lipoproteins to oxidation also was noted during AGE
administration compared with the placebo period. We conclude that the beneficial
effect of garlic preparations on lipids and blood pressure extends also to
platelet function, thus providing a wider potential protection of the
cardiovascular system.
PMID- 9641476
TI - Effects of troglitazone and pioglitazone on cytokine-mediated endothelial cell
proliferation in vitro.
AB - We examined whether troglitazone and pioglitazone, antidiabetic
thiazolidinediones, would directly induce endothelial cell proliferation or
influence cytokine-driven proliferation in vitro. Monolayers of Balb/c mouse
aortic endothelial cells were treated with troglitazone or pioglitazone in the
absence of fetal bovine serum. Endothelial cells also were exposed to varying
concentrations of basic fibroblast growth factor (bFGF) or insulin with or
without either thiazolidinedione. After 48 h, 3-[4,5-dimethylthiozol-2-yl]-2,5
diphenyl tetrazolium bromide (MTT) assays were performed to quantitate
endothelial cell proliferation by using the various treatment regimens. The data
demonstrate that the antidiabetic thiazolidinediones troglitazone and
pioglitazone negligibly affect direct endothelial cell proliferation in vitro.
Furthermore, troglitazone and pioglitazone significantly inhibit bFGF-induced
endothelial cell mitogenesis, whereas only high concentrations of troglitazone
affect insulin-mediated proliferation.
PMID- 9641477
TI - Effects of amiodarone and desethylamiodarone on the inward rectifying potassium
current (IK1) in rabbit ventricular myocytes.
AB - We examined the effects of amiodarone (AMI) and desethylamiodarone (DAM) on whole
cell inward rectifying potassium current (IK1) in freshly isolated adult rabbit
ventricular myocytes by using the whole-cell voltage-clamp technique, as an index
of their effects on resting membrane resistance (Rm). Under control conditions,
the current showed a strong inward rectification with a maximal inward current
measured at -130 mV of -26.4 +/- 1.3 pA/pF and a maximal outward current measured
at -50 mV of 3.5 +/- 0.3 pA/pF The current also exhibit a time-dependent
activation, with a time constant of activation (tau(a)) that increased with
depolarization. The maximal slope conductance normalized to cell capacitance was
0.509 +/- 0.019 nS/pE After exposure to both DAM (50 microM; n = 8) and AMI (50
microM; n = 7), rapid decrease in inward IK1 was observed. Block was restricted
almost exclusively to the inward component. DAM caused a significant reduction of
the maximal inward current (-20.0 +/- 2.0 pA/pF; p < 0.05), whereas AMI induced
an even greater reduction of the same component (-14.1 +/- 1.2 pA/pF; p < 0.05
with respect to control and to DAM). The outward component of IK1 was not changed
by either AMI or DAM (4.0 +/- 0.3 pA/pF and 3.4 +/- 0.4 pA/pF, respectively). AMI
and DAM also decreased the maximal slope conductance significantly (0.297 +/-
0.019 nS/pF and 0.421 +/- 0.038 nS/pF, respectively). In addition, AMI but not
DAM significantly increased the tau(a). However, the voltage dependence of the
acceleration of tau(a) remained unchanged after both AMI and DAM exposure. These
results allow us to conclude that AMI may induce a greater increase in the
resting Rm than its main metabolite. This effect may counterbalance, at least in
part, the conduction slowing due to its sodium channel-blocking properties.
PMID- 9641478
TI - Maintained vasodilatory response to cromakalim after inhibition of nitric oxide
synthesis.
AB - Activation of vascular smooth-muscle adenosine triphosphate-sensitive potassium
channels (KATP channels) causes membrane hyperpolarization, reduced entry of Ca2+
through L-type voltage-gated Ca2+ channels, and subsequent smooth-muscle
relaxation. Conversely, opening of endothelial KATP channels elicits
hyperpolarization but may induce Ca2+ influx and stimulation of endothelium
derived nitric oxide (EDNO) because these cells appear not to possess L-type Ca2+
channels. We therefore hypothesized that EDNO contributes to KATP channel
mediated vasodilation. To test this hypothesis, we examined vasodilatory
responses to the KATP channel opener cromakalim in conscious rats, perfused rat
tail artery segments, and isolated perfused rat lungs in the presence or absence
of the EDNO synthesis inhibitor Nomega-nitro-L-arginine (L-NNA). Additionally, we
compared the effect of cromakalim with the EDNO-dependent dilator bradykinin on
NO production and intracellular Ca2+ in cultured rat pulmonary artery endothelial
cells. Vasodilatory profiles to cromakalim were unaffected by L-NNA in conscious
rats, tail arteries, and isolated lungs. Consistent with these results,
cromakalim had no apparent effect on either NO synthesis or Ca2+ levels in
cultured endothelial cells. These data suggest a lack of a role for EDNO in
contributing to KATP-channel-mediated vasodilation in the rat.
PMID- 9641479
TI - Combined effects of alcohol and nicotine on cardiovascular performance in a
canine model.
AB - Alcohol and tobacco consumption are correlated. Smokers consume more alcohol than
do nonsmokers, and alcohol consumers smoke more than do teetotalers. The
independent effects of alcohol and nicotine on the cardiovascular system are well
documented, but combined effects of short-term administration are unknown. This
experimental work was designed to study the effects due to short-term
administration of alcohol and nicotine on cardiovascular system. In phase I, 30
experiments were performed to study the dose-response curve of both the drugs. In
phases II and III, 15 dogs were subjected to 30 experiments. In phase II,
ethanol, 400 mg/kg, was given i.v., followed by nicotine 50 microg/kg, i.v., and
in phase III, sequence of drug administration was reversed to study the effects
on hemodynamics and coronary artery blood flow. The dose-response curve
established the i.v. dose of ethanol, 400 mg/kg, and nicotine, 50 microg/kg.
Ethanol administration caused a nonsignificant increase in heart rate (HR), mean
arterial pressure (MAP), left ventricular systolic pressure (LVS), and left
ventricular mechanical work (LVMW), and a decrease in maximal rate of increase of
LV pressure per second (dP/dt), stroke volume (SV), and systemic vascular
resistance (SVR). Left ventricular end-diastolic pressure (LVEDP), pulmonary
artery mean pressure (PAM), right atrial pressure (RAP), pulmonary vascular
resistance (PVR), myocardial oxygen consumption (MVO2), and average peak velocity
of coronary blood flow (APV) had mild significant increases as compared with
controls. Nicotine significantly increased heart rate, mean arterial pressures,
LVEDP, and pulmonary artery, pulmonary capillary wedge, and right atrial
pressures. Nicotine increased dP/dt (2,062-3,188; p < 0.006) and decreased APV (9
to 8; p < 0.03). Combined ethanol followed by nicotine had synergistic increase
in HR, SD, MAP, LVS, LVEDP, pulmonary pressures, CO, SV, dP/dt (2,184 > 5,206; p
< 0.005), MVO2, and LVMW. However, the excitatory effects of nicotine were
attenuated when ethanol was administered after nicotine (dP/dt, reduced from
2,058 to 1,653; p < 0.04, and APV increased from 10 to 12; p < 0.02). We conclude
that ethanol increased APV but had nonsignificant effects on the hemodynamics,
whereas nicotine reduced the APV and had significant excitatory responses. In
combination (i.v.), ethanol + nicotine produced significant synergistic
excitatory effects. On the other hand, the nicotine + ethanol combination
increased APV and caused attenuation of the excitatory effects of nicotine in
dogs.
PMID- 9641480
TI - Depression of efferent parasympathetic control of heart rate in rats with
myocardial infarction: effect of losartan.
AB - Heart failure is associated with attenuation of parasympathetic nervous function
and enhanced renin-angiotensin activity. We tested whether there was a
dysfunction in the efferent cholinergic neurotransmission in the heart of rats
with chronic myocardial infarction (MI) and the potential role of angiotensin II
(Ang II) receptors in such changes. Rats with MI and sham-operation were
anesthetized, and heart rate (HR) reduction in response to vagal nerve
stimulation was measured before and after losartan administration (10 mg/kg,
i.v.) in the presence or absence of physostigmine to inhibit
acetylcholinesterase. Infarcted rats had an average infarct size (IS) of 38% of
the left ventricle (LV), depressed LV dP/dtmax, elevated LVEDP, and cardiac
hypertrophy. Nerve stimulation (1-16 Hz) reduced HR in a frequency-dependent
manner. The bradycardiac responses were significantly attenuated in infarcted
versus control rats (p < 0.01), indicating an impaired efferent vagal tone. In
contrast, the bradycardic response to exogenous acetylcholine was similar in both
groups, implying an unchanged muscarinic receptor responsiveness in hearts with
MI. HR response to nerve stimulation was potentiated by losartan in infarcted
rats by 21 +/- 4 versus 4 +/- 2 beats/min (p < 0.01) but was unaffected in
control rats. This effect of losartan was inversely related to the extent of
attenuation of vagally mediated HR reduction. IS was correlated with both the
extent of attenuation in vagally mediated bradycardia and the effect of losartan.
In conclusion, the efferent vagal control of HR is attenuated in rats with MI and
heart failure. This attenuation may be partly due to a presynaptic inhibition of
acetylcholine release through the tonic activation, by Ang II, of neuronal AT1
receptors.
PMID- 9641481
TI - Azimilide causes reverse rate-dependent block while reducing both components of
delayed-rectifier current in canine ventricular myocytes.
AB - Most class III antiarrhythmic drugs reduce the rapidly activating component of
delayed-rectifier current (IKr) without affecting the slowly activating component
(IKs). Recently the novel antiarrhythmic agent azimilide (NE-10064) was reported
to enhance IKs at low (nanomolar) concentrations and to block both IKr and IKs at
higher (micromolar) concentrations. Further to understand the electrophysiologic
effects of azimilide, we compared its effects on IKr and IKs (by using whole cell
clamp techniques) and action potentials (microelectrode and perforated-patch
techniques) on canine ventricular myocytes. A lower azimilide concentration (50
nM) did not enhance IKs. In contrast, a therapeutic azimilide concentration (2
microM) was equieffective in reducing IKr (300-ms isochrones) and IKs (3-s
isochrones) by approximately 40% during depolarizing test pulses, as well as
reducing IKr (38% decrease) and IKs (33% decrease) tail currents on
repolarization. Block of IKs was independent of voltage at positive test
potentials. In action-potential studies, 50 nM azimilide had no effect on the
action-potential duration (APD), whereas 2 microM azimilide delayed
repolarization and caused reverse rate-dependent effects on the APD. Whereas the
extent of APD prolongation by azimilide was not correlated with the drug-free
APD, azimilide preferentially exaggerated the APD-rate relationship of myocytes
displaying the steepest APD-rate relationship under drug-free conditions. In
conclusion, therapeutic concentrations of azimilide that cause comparable
reduction of canine ventricular IKr and IKs exert reverse rate-dependent effects,
which are dependent on the steepness of the APD-rate relationship.
PMID- 9641483
TI - Arterial vasodilation and vascular connective tissue changes in spontaneously
hypertensive rats.
AB - Arterial hypertrophy in response to hypertension includes increases in the
connective tissue proteins elastin and collagen. Regression of arterial
hypertrophy depends not only on blood pressure normalization but also on the
specific antihypertensive treatment. Consequently, each drug class may exert an
influence on connective tissue proteins. We evaluated the arterial connective
tissue response of 16-week-old spontaneously hypertensive rats (SHRs) to
treatment with minoxidil, 120 mg/L, drinking water for 10 weeks. Despite a
decrease in blood pressure, minoxidil had no effect on arterial weight or
collagen content but increased elastin content in the abdominal aorta, renal, and
superior mesenteric arteries. The increase in elastin content in the abdominal
aorta and superior mesenteric artery was accompanied by a decrease in tissue
elastase activity. Thus the minoxidil-induced increase in arterial elastin
content may be related to a direct effect of the drug to decrease elastase
activity in these tissues.
PMID- 9641482
TI - Baroreflex-mediated bradycardia is blunted by intravenous mu- but not kappa
opioid agonists.
AB - To assess the cardiovascular effects of systemically administered opioid
agonists, changes in blood pressure and heart rate were observed after
intravenous (i.v.) administration of U50,488H (trans-3,4-dichloro-N-[2-(1
pyrrolidinyl) cyclohexyl]benzeneacetamide), a selective kappa-opioid receptor
agonist, and DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol), a selective mu-opioid-receptor
agonist. Intravenous administration of U50,488H (1.2 mg/kg) and DAMGO (0.3 mg/kg)
to the awake sheep resulted in an immediate increase in blood pressure. The
pressor response to U50,488H was accompanied by an increase in heart rate. In
contrast, there was no accompanying change in heart rate in response to DAMGO. We
hypothesized that the lack of a reflex bradycardia to the pressor responses of
both the mu- and kappa-opioid-receptor agonists was due to a blunting of
baroreflex-mediated bradycardia. The reflex bradycardia to norepinephrine (0.6
microg/kg/min) was significantly reduced in the presence of DAMGO but not
U50,488H. In view of the lack of effect of U50,488H on the baroreflex, we further
hypothesized that the tachycardia it elicited was due to an increase in
sympathetic activity. Pretreatment with propranolol (0.1 mg/kg) completely
blocked the tachycardia elicited by U50,488H. These data suggest that the lack of
a reflex bradycardia to the pressor response of DAMGO is due to a blunting of
baroreflex-mediated bradycardia. In contrast, the increase in heart rate caused
by U50,488H is mediated by sympathetic activation of the heart.
PMID- 9641484
TI - Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta
hydroxylase inhibitor.
AB - Nepicastat (RS-25560-197) is a novel, selective, and potent inhibitor of dopamine
beta-hydroxylase, which modulates catecholamine levels (reduces norepinephrine
and elevates dopamine) in cardiovascular tissues. This study was designed to
evaluate the cardiovascular effects of nepicastat. Acute oral administration of
nepicastat (0.3, 1, 3, 10, and 30 mg/kg) produced attenuation of the pressor and
positive chronotropic responses to preganglionic sympathetic nerve stimulation
(about twofold to sixfold shift in the frequency-response curve) in pithed
spontaneously hypertensive rats (SHRs). In inactin-anesthetized SHRs, the
antihypertensive effects of nepicastat (3 mg/kg, i.v.) were accompanied by a
significant decrease in renal vascular resistance (38%), a tendency toward an
increase in renal blood flow (22%), and no adverse effects on urine output and
Na/K excretion. In conscious, unrestrained, telemetry-implanted SHRs, nepicastat
(30 and 100 mg/kg/day for 30 days) produced dose-dependent decreases in mean
arterial blood pressure (peak decrease of 20 and 42 mm Hg, respectively) without
evoking reflex tachycardia. Long-term, concurrent administration of nepicastat
(30 mg/kg/day, p.o.) and a subthreshold dose of enalapril (1 mg/kg/day, p.o.)
produced greater antihypertensive effects than those produced by nepicastat
alone. In normal dogs, nepicastat (5.0 mg/kg, p.o., b.i.d., for 4.5 days) blunted
the positive chronotropic and pressor response to tyramine. These findings
suggest that nepicastat functionally modulates sympathetic drive to
cardiovascular tissues and may be of value in the treatment of cardiovascular
disorders associated with overactivation of the sympathetic nervous system such
as hypertension and congestive heart failure.
PMID- 9641485
TI - Inhibition of myocardial lesions in the JCR:LA-corpulent rat by captopril.
AB - The JCR:LA-cp rat is a unique strain that, if homozygous for the autosomal
recessive cp gene, is obese and exhibits the metabolic syndrome of insulin
resistance, hyperinsulinemia, and hypertriglyceridemia. Obese male rats
spontaneously develop advanced atherosclerosis and ischemic myocardial lesions.
The angiotensin-converting enzyme inhibitor, captopril, was administered to obese
rats at 30 mg/kg body weight from 6 to 39 weeks of age. There were no significant
changes in food consumption or body weights of the treated animals. Insulin
sensitivity was not improved. Plasma insulin levels were unaltered, but the
volume density of the islets of Langerhans was halved, reflecting both reduced
hyperplasia and a more normal islet structure. Triglyceride concentrations were
not reduced, but unesterified cholesterol and cholesteryl esters decreased by 50%
and 34%, respectively (p < 0.01). The impaired nitric oxide-mediated vascular
relaxation of the obese rats was not improved, and the relaxant sensitivity to
acetylcholine as indicated by the median effective concentration (EC50) was
reduced. In vitro, captopril significantly reduced the basal tension of aortic
rings from untreated rats, antagonized the contractile effects of norepinephrine,
and induced complete relaxation of the contraction in response to 10(-7) M
norepinephrine. The severity of spontaneous, raised atherosclerotic lesions of
the aortic arch at age 39 weeks was not significantly decreased by captopril
treatment. In contrast, the frequency of ischemic myocardial lesions was reduced
by 78% (p < 0.01). The protective effects of captopril on the heart and pancreas
in this animal model of type II diabetes and atherosclerosis are probably the
result of its bradykinin-enhancing effects.
PMID- 9641486
TI - Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and
Caucasians.
AB - An understanding of why people smoke cigarettes can have an important impact on
smoking prevention and cessation. People smoke cigarettes to maintain nicotine
levels in the body, and nicotine has been implicated in the stimulation of brain
reward mechanisms via central neuronal dopaminergic pathways. In this study, we
evaluated the association of smoking and smoking cessation with a dopamine D4
receptor 48-bp variable nucleotide tandem repeat polymorphism in which the seven
repeat allele (D4.7) reduces dopamine affinity. Smokers (n = 283) and nonsmokers
(n = 192) were recruited through local media for a case-control study of smoking.
After giving informed consent and answering a behavioral questionnaire, smokers
underwent a single minimal-contact session of smoking cessation counseling and
then were followed for up to 1 year. The frequency of the dopamine D4 receptor
genetic polymorphism using PCR was determined, and individuals were classified by
the number of repeat alleles (two to five repeats as S and six to eight repeats
as L). Persons with those genotypes including only S alleles (homozygote S/S)
were compared with those with at least one L allele (heterozygote S/L and
homozygote L/L). Chi2 tests of association, Fisher's exact test, and Student's t
test were used. Ps were two-tailed. The data show that African-Americans (n = 72)
who had at least one L allele had a higher risk of smoking (odds ratio, 7.7; 95%
confidence interval, 1.5-39.9; P = 0.006), shorter time to the first cigarette in
the morning (P = 0.03), and earlier age at smoking initiation (P = 0.09) compared
with homozygote S/S genotypes. After smoking cessation counseling, none of the
African-American smokers with an L allele were abstinent at 2 months, compared
with 35% of the smokers who were homozygote S/S (P = 0.02). The analysis of
Caucasians (n = 403) did not suggest a similar smoking risk for the D4 genotypes
(odds ratio, 1.0; 95% confidence interval, 0.6-1.6; P = 0.90), or smoking
cessation (P = 0.75). Although the number of African-Americans is small, this
study is consistent with the hypothesis that the L alleles increase the risk of
smoking because these individuals are prone to use nicotine to stimulate synaptic
dopamine transmission. If replicated, the data indicate that a single minimal
contact session of cessation counseling, similar to what is typically provided in
primary care physician offices, is ineffective in African-American smokers who
have at least one L allele. The finding of an effect for these polymorphic loci
in African-Americans, but not Caucasians, suggests that the variable nucleotide
tandem repeat studied here is a marker for another polymorphic site in African
Americans, but not in Caucasians.
PMID- 9641487
TI - Can strategies used by statewide tobacco control programs help smokers make
progress in quitting?
AB - Many states have recently adopted programs to encourage smokers to quit. Here, we
seek evidence that strategies generally used by these programs have the potential
to influence smoking cessation. In California, 1,736 smokers from a population
based telephone survey were interviewed in 1990 and 1992. We examined the
association of demographic and program-related variables (reporting of work area
smoking bans; belief in the harmfulness of environmental tobacco smoke, including
in-home smoking restrictions; and quitting assistance) with quitting progress.
Smokers were categorized into levels in a previously developed Quitting
Continuum, which considers their addiction level and quitting history. Smokers in
each higher continuum category had an increased likelihood of future successful
cessation. Smokers progressed if they were at a higher continuum level in 1992
than in 1990. College graduates showed 2.3 times more progress than did high
school dropouts. Smokers reporting work area smoking bans showed 1.6 times more
progress than did workers not reporting such restrictions. Smokers with the
strongest beliefs (home smoking restrictions) regarding the harmfulness of
environmental tobacco smoke showed 3.4 times more progress than smokers with no
belief. Smokers who reported having some form of cessation assistance showed 3.0
times more progress. The more program-related factors were reported, the higher
the rate of progress was: 13.1% for those reporting no factors, 23.4% for one
factor, and 40.6% for two or more. These results suggest but do not prove that
strategies promoted by statewide tobacco control programs can potentially be
effective and that these efforts should be continued and expanded.
PMID- 9641488
TI - Reduced DNA repair capacity in head and neck cancer patients.
AB - Head and neck cancers (HNCs) are malignancies that can be induced by tobacco use,
although host-specific factors such as the DNA repair capacity (DRC) may modulate
individual susceptibility to tobacco carcinogenesis. To test the hypothesis that
genetically determined DRC modulates HNC susceptibility, we measured the DRC in
the peripheral blood lymphocytes of 55 patients with newly diagnosed, previously
untreated HNC and 61 healthy controls by the host-cell reactivation assay using a
reporter gene damaged by benzo(a)pyrene diol epoxide, an ultimate tobacco-related
carcinogen. The mean DRC was significantly lower in cases (8.6%) than it was in
controls (12.4%; P < 0.001). The DRC was an independent risk factor for HNC (P <
0.01); those in the middle and lowest tertiles of DRC had increased odds ratios
[2.17 (95% confidence interval, 0.74-6.39) and 4.27 (confidence interval, 1.45
12.5), respectively] for HNC. These findings suggest that individuals with
reduced DRC may be at increased risk of developing HNC.
PMID- 9641489
TI - Exfoliated oral cell messenger RNA: suitability for biomarker studies.
AB - The efficacy of chemoprevention trials can be improved by the use of biomarkers
of carcinogenesis that serve as surrogate end points. The aim of this study was
to assess the perspectives of using mRNA isolated from oral exfoliated cells for
biomarker research in chemoprevention of upper aerodigestive tract cancer. When
using reverse transcription-PCR in combination with Southern blotting and
hybridization, it was possible to detect transcripts from only five cells. With
the quantitative RNase protection assay, we could only detect highly abundant
transcripts. The integrity of the RNA was verified by Northern blotting, which
showed a variable degree of degradation, depending on the gene studied.
Interestingly, although specific transcripts were found to be intact to a certain
extent, the rRNA appeared to be completely degraded, suggesting that a specific
protein synthesis shut-off mechanism exists in terminally differentiated oral
epithelial cells. Altogether, this differential RNA degradation makes accurate
measurement of transcript levels of most genes, as determined in exfoliated oral
cells, unreliable. Because this RNA degradation process is likely to start before
the cells are shed from the tissue, the results of measurements of transcript
levels in biopsies of oral tissue should be interpreted with caution.
PMID- 9641490
TI - Short-term follow-up after endoscopic mucosectomy of early esophageal cancer and
aldehyde dehydrogenase-2 genotype in Japanese alcoholics.
AB - The risk of the future development of primary esophageal cancer after endoscopic
esophageal mucosal resection of esophageal cancer is not known; hence, there are
no established guidelines for follow-up surveillance programs. Simultaneous
occurrence of multiple cancers associated with esophageal cancer is common among
heavy drinkers who have the inactive form of aldehyde dehydrogenase-2 (ALDH2) as
a risk factor. Thirty-four Japanese male alcoholics with intraepithelial or
mucosal squamous cell carcinoma in the esophagus were treated by endoscopic
esophageal mucosal resection, followed by endoscopy and esophageal iodine
staining, to find the additional development of primary esophageal cancer.
Primary esophageal squamous cell carcinoma was detected in nine patients (26.5%)
at 3-21 months after the first cancer diagnosis. Cancer occurred more frequently
in patients with inactive ALDH2 than it did in those with active ALDH2 [42.1% (8
of 19) versus 6.7% (1 of 15), P = 0.047], and it occurred more frequently in
those with multiple esophageal cancers than it did in those without them [60.0%
(6 of 10) versus 12.5% (3 of 24), P = 0.009]. Kaplan-Meier estimates of the
proportions of patients with additional primary esophageal cancers showed that
patients with inactive ALDH2 (P = 0.024) or multiple esophageal cancers (P =
0.007) had a significantly increased likelihood of the development of additional
cancer. Close follow-up examinations using endoscopy and iodine staining are
needed for such high-risk patients.
PMID- 9641491
TI - Anthropometric and hormone effects of an eight-week exercise-diet intervention in
breast cancer patients: results of a pilot study.
AB - To assess the feasibility of an exercise-diet intervention in sedentary,
overweight breast cancer patients, we conducted a pilot 8-week intervention.
Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast
cancer patients, ages 25-75 years, who were identified through two Seattle breast
surgery practices and the University of Washington Breast Clinic. Ten patients
were eligible and interested and were enrolled in the intervention, which
consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20%
of calories from fat) diet. Nine patients completed the program; all adhered well
to the intervention and data collection protocol. The patients, ages 40-74 years,
lost, on average, 2.6 pounds of body weight, 3.4 cm in waist circumference, 4.6
cm in hip circumference, 2.3% body fat, 3.3 systolic blood pressure points, 0.67
diastolic blood pressure points, and 4.0 pulse beats/min, and they gained an
average of 2.3% lean mass. Slight, nonsignificant decreases were observed in
serum concentration of total and free estradiol, estrone sulfate, total
testosterone, androstenedione, and dehydroepiandrosterone. These pilot data
indicate that breast cancer patients are highly motivated to join and adhere to
an intense exercise-diet intervention and can experience significant measurable
changes in anthropometric and fat mass measures.
PMID- 9641492
TI - Association between high-density lipoprotein cholesterol and breast cancer varies
by menopausal status.
AB - A nested case-control study was conducted to investigate the hypothesis that
women with high levels of high-density lipoprotein cholesterol (HDL-C) are at an
increased risk of breast cancer. The source population was a cohort of 95,000
women enrolled in the Kaiser Permanente Medical Care Program who underwent a
routine multiphasic health examination between 1964 and 1971. From the more than
2,000 breast cancer cases diagnosed in this cohort, 200 cases were randomly
selected for this study. For each case, one control who matched on age and date
of examination was chosen. Lipid and lipoprotein levels were measured in archived
serum samples collected at the time of the women's examinations. Breast cancer
risk factor information was obtained from questionnaires completed by the women
when their blood was drawn and was supplemented with information from medical
records. HDL-C levels were not significantly different between the cases and
controls overall; however, a statistically significant interaction between the
HDL-C level and menopausal status at diagnosis was detected. Premenopausal cases
had mean HDL-C levels 3.48 mg/dl lower than matched controls [95% confidence
interval (CI), -7.05, 0.09], whereas postmenopausal cases had levels 2.05 mg/dl
higher than controls (95% CI, -0.94, 5.03). In multivariate conditional logistic
regression analyses, the odds ratio associated with each 1 mg/dl increase in HDL
C was 0.96 (95% Cl, 0.93-1.0) for premenopausal women and 1.02 (95% CI, 0.99
1.05) for postmenopausal women. Although many breast cancer risk factors are
associated with high HDL-C, the relationship between breast cancer and HDL-C was
independent of other factors evaluated.
PMID- 9641493
TI - Relative abundance of organochlorine pesticides and polychlorinated biphenyls in
adipose tissue and serum of women in Long Island, New York.
AB - Some organochlorine pesticides (OCPs) and PCBs are under investigation as
possible risk factors for breast cancer because of their estrogenic properties
and widespread presence in the environment. It is important to know whether
adipose tissue used by some investigators and serum assays used by others can
provide comparable information on body burden. Concentrations of seven OCPs or
their breakdown products as well as 14 PCB congeners were measured in the adipose
tissue and serum of 293 women enrolled as controls in a case-control study of
environmental factors for breast cancer in Long Island, New York, a high-risk
region. Adipose OCP/PCB levels were measured using a supercritical fluid
extraction method developed by the authors. 1,1-Dichloro-2,2-di(4
chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples;
two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and
hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho
hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and
2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of
serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total
pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl
comprised 24% of adipose and 21% of serum PCBs. The relative concentration
patterns of the 14 PCB congeners were similar to those reported in other human
studies and were also typical of patterns reported in environmental samples from
various biota, including mammals and birds, but differed substantially from
patterns reported in occupationally exposed workers. All adipose-serum
correlations for pesticides and most PCBs were statistically significant. Either
serum or adipose OCP/PCB levels of a variety of environmental organochlorine
compounds may serve as useful biomarkers of body burden.
PMID- 9641494
TI - A subset of metastatic human colon cancers expresses elevated levels of
transforming growth factor beta1.
AB - Although transforming growth factor (TGF)-beta1 is a potent growth inhibitor of
normal epithelial cells including colonocytes, TGF-beta1 has also been implicated
as an enhancer of colon cancer metastasis. Decreasing TGF-beta1 protein levels in
the metastatic U9 colon cancer cell line by antisense methodology decreased both
U9 cell metastasis to the liver and s.c. tumor formation in a nude mouse system,
and the tumors that did arise had regained TGF-beta1 expression (F. Huang et al,
Cell Growth Differ., 6: 1635-1642, 1995). In addition, in a clinical
immunohistochemistry study, colon cancers with elevated TGF-beta1 protein levels
were found to be 18 times more likely to recur as distant metastases than colon
cancers expressing low TGF-beta1 levels, after resection of the primary tumor (E.
Friedman et al, Cancer Epidemiol. Biomark. Prev., 4:549-554, 1995). Because both
studies implicated TGF-beta1 in colon cancer metastasis, we wished to know
whether a selection bias for TGF-beta1 was maintained in metastatic cells or was
only a property of the primary site tumors that were likely to metastasize. TGF
beta1 levels were measured using two different antibodies in paired primary site
cancers and their metastases by immunohistochemistry and, in selected cases, by
Western blot analysis. In 16 of 21 cases (76%) with antibody G and 23 of 31 cases
(74%) with antibody P, higher expression of TGF-beta1 was found in colon cancer
cells invading local lymph nodes compared with primary site colon cancer cells,
or (2 and 6 cases, respectively) high TGF-beta1 expression in the primary site
cancer was maintained in invasive cells. Analysis by Western blotting using both
antibodies also demonstrated that higher levels of TGF-beta1 protein were found
in metastases compared with the primary site tumor or normal tissue. Additional
cases of paired primary site colon cancer, local lymph node metastases, and
cancer cells metastasizing to distant sites were examined. In six of eight such
cases (75%), TGF-beta1 levels were increased in both invasive cell populations
compared with the primary site cancer (five cases), or high levels in the primary
site cancer were maintained in the metastatic cells (one case). These data
suggest that TGF-beta1 plays a role in promoting colon cancer metastasis
throughout the metastatic process in roughly 75% of cases. TGF-beta1 may increase
metastasis by paracrine mechanisms, such as suppression of local immune response
or increased angiogenesis, as was seen with the U9 cell line. In those cancers
with nonmutated TGF-beta receptors and nonmutated smad proteins like U9 cells,
TGF-beta1 could also act in an autocrine manner to increase invasion by
increasing cell motility (Hsu et al., Cell Growth Differ., 5: 267-275, 1994).
PMID- 9641495
TI - Heterogeneity of guanylyl cyclase C expressed by human colorectal cancer cell
lines in vitro.
AB - In humans, guanylyl cyclase C (GCC) is expressed by mucosal cells lining the
intestine, from the duodenum to the rectum, but not by extraintestinal tissues.
Expression of GCC persists after mucosal cells undergo neoplastic transformation,
and this protein has been identified in all primary and metastatic colorectal
tumors examined to date, suggesting that GCC may be a highly specific biomarker
for colorectal cancer. The utility of GCC as a diagnostic biomarker and
therapeutic target is predicated, in part, on defining the variability of its
expression in colorectal cancer cells. Similarly, the utility of this biomarker
to define tumor burden in diagnosing, staging, and postoperative surveillance of
patients is predicated on quantifying GCC expression in cancer cells in tissues
and blood. The present studies examined the heterogeneity of GCC expression in
eight human colorectal carcinoma cell lines in vitro representing the full
spectrum of cytological differentiation. Quantification of GCC expression by
ligand binding and stimulation of cGMP accumulation demonstrated that functional
GCC expression is heterogeneous in different colorectal cancer cell lines.
Qualitative reverse transcription (RT)-PCR demonstrated that all colorectal
cancer cells examined expressed GCC mRNA. However, GCC expression varied 100-fold
in different colorectal cancer cell lines, determined by a novel quantitative RT
PCR assay. Functional and molecular expressions of GCC were unrelated to the
differentiation state of cancer cells. These studies suggest that GCC is
heterogeneously expressed by colorectal cancer cells in vitro and suggest a role
for quantitative RT-PCR analysis in the development of diagnostic tests using GCC
as a biomarker for metastatic colorectal cancer.
PMID- 9641497
TI - Predictors of dietary heterocyclic amine intake in three prospective cohorts.
AB - Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids
and creatinine. Although recognized as mutagenic, the etiological role of HCA in
human cancer is unclear, due to the lack of information on the effect of typical
food cooking methods on HCA concentrations and on variation in HCA exposure in
populations. We estimated overall daily dietary HCA intake and variation in
intake between individuals, using recent data on HCA concentrations in various
meats prepared by cooking methods, temperatures, and times common in United
States in the 1990s. Random samples of 250 participants from each of three large
prospective cohorts were mailed a questionnaire to assess frequency of
consumption, cooking method, and typical outside appearance of pan-fried,
broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried,
microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The
2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6
phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8
trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in
composite samples by solid-phase extraction and high-performance liquid
chromatography, were assigned to each food, cooking method, and doneness level.
The dietary reports showed approximately 30-fold relative variation in 2-amino
3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6
phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8
trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA
intake were compared (90th/10th percentile value). These reported variations in
HCA exposure among participants in these three large cohorts indicates that
estimation of HCA intake and determination of association with disease risk are
feasible, if additional information on meat cooking methods is obtained.
PMID- 9641496
TI - K-ras mutation in focal proliferative lesions of human pancreas.
AB - The K-ras gene is mutated in > or =75% of human pancreatic adenocarcinomas and in
a number of hyperplastic ductal lesions from noncarcinoma patients. In this
study, the incidence of K-ras mutation was determined in a spectrum of focal
proliferative pancreatic lesions to evaluate their preneoplastic significance.
PCR-based mutation-enriched RFLP analysis was used to identify mutations in codon
12. Immunostaining for Ki67 and p53 was also performed. Forty-seven % of
intraductal nonpapillary hyperplasias (8 of 17) contained codon 12 mutations, as
did 55% of adenomatoid hyperplasias (6 of 11). This rate increased to 61% in
papillary hyperplasias (27 of 44) and to 78% when there was severe dysplasia (7
of 9). The fraction of cells staining for the Ki67 proliferation marker showed a
general correlation with the rate of K-ras mutation. Nuclear staining for p53
protein was seen only in two ductal lesions with severe dysplasia. No mutations
were found in normal acinar tissue (n = 38), squamous metaplasia (n = 13), ductal
complexes (n = 8), or focal acinar cell dysplasia (n = 5). There seemed to be a
general correlation of proliferative potential with the presence of K-ras
mutation in ductal lesions. However, because of the high prevalence of lesions
with K-ras mutations, we conclude that this mutation alone cannot be taken as
proof of significant risk for progression to carcinoma. Efforts to use the
presence of K-ras mutations in DNA harvested from pancreatic juice or duodenal
aspirates as an approach for diagnosis of occult pancreatic carcinoma seem
vulnerable to a high false-positive rate.
PMID- 9641498
TI - CG island methylation changes near the GSTP1 gene in prostatic intraepithelial
neoplasia.
AB - Prostate intraepithelial neoplasia (PIN) is a purported prostate cancer precursor
lesion and a candidate biomarker for efficacy assessment in prostate cancer
chemoprevention trials. Loss of expression of the pi-class glutathione S
transferase enzyme GSTP1, which is associated with the hypermethylation of
deoxycytidine residues in the 5'-regulatory CG island region of the GSTP1 gene,
is a near-universal finding in human prostate cancer. GSTP1 expression was
assessed by immunohistochemistry in 60 high-grade PIN samples adjacent to and
distant from prostate adenocarcinoma. Whereas abundant enzyme polypeptide
expression was evident in all normal prostatic tissues, all samples of high-grade
PIN and adenocarcinoma were completely devoid of GSTP1. DNA from 10 high-grade
PIN lesions was analyzed for GSTP1 CG island methylation changes using a PCR
technique targeting a polymorphic (ATAAA)n repeat sequence in the promoter region
of the GSTP1 gene. Somatic GSTP1 CG island methylation changes were detected in
DNA from 7 of the 10 PIN lesions. Allele discrimination was possible for 5 of the
10 DNA samples: 2 of the 5 samples exhibited DNA methylation changes at both
alleles; whereas 3 samples displayed no DNA methylation changes at either allele.
GSTP1 CG island methylation changes were present in each of the five homozygous
samples. Hypermethylation of the 5'-regulatory region of the GSTP1 gene may serve
as an important molecular genetic biomarker for both prostate cancer and PIN. The
finding of frequent GSTP1 methylation changes in PIN and prostate cancer supports
a role for PIN lesions as a prostate cancer precursor and may provide insight to
the molecular pathogenesis of prostate cancer.
PMID- 9641499
TI - The association of plasma micronutrients with the risk of cervical dysplasia in
Hawaii.
AB - Limited data from hematological studies suggest that certain nutrients, including
carotenoids, tocopherols, and vitamin C, may protect against malignant change in
cervical tissue. Recognizing that human papillomavirus (HPV) infection induces
most neoplastic transformation of cervical tissue, the authors conducted a case
control study to examine the association of plasma micronutrient concentrations
with the risk of cervical dysplasia after careful adjustment for HPV infection,
using a sensitive and reliable HPV detection method. The sample included 147
multiethnic women, between 18 and 65 years of age, with biopsy-confirmed squamous
intraepithelial lesions (SILs) of the cervix and 191 clinic controls identified
between 1992 and 1996. Cases were identified through cytology and pathology logs
in three clinics on Oahu, Hawaii. Controls were selected randomly from admission
logs of the participating clinics. In-person interviews were conducted in the
subjects' homes, and a fasting blood sample was drawn to measure plasma levels of
lutein, lycopene, cryptoxanthin, total carotene, retinol, tocopherol, ascorbic
acid, and cholesterol. The presence and type of HPV was determined in exfoliated
cell samples using PCR dot blot hybridization. Mean plasma lycopene, total
cryptoxanthin, and alpha-cryptoxanthin levels were lower among cases than
controls. We found an inverse dose-response of alpha-cryptoxanthin, total
tocopherol, and alpha-tocopherol to the odds ratios for cervical SIL after
adjustment for HPV and other confounders. The odds ratio among women in the
highest compared with the lowest quartile was 0.3 (95% confidence interval, 0.1
0.7) for alpha-cryptoxanthin and 0.3 (95% confidence interval, 0.1-0.8) for alpha
tocopherol. Negative trends in the odds ratios were suggested for other
carotenoids and vitamin C, but these were weak, and confidence intervals were
wide. Our results support existing evidence that high plasma levels of
antioxidants may reduce the risk of cervical SILs independent of HPV infection.
These findings are significant because diet is potentially modifiable, and
nutrition education and dietary intervention might be targeted at specific high
risk groups.
PMID- 9641500
TI - Biomonitoring of United States Army soldiers serving in Kuwait in 1991.
AB - Biomarkers of polycyclic aromatic hydrocarbon (PAH) exposure and genetic
biomarkers of potential cancer susceptibility were determined in a group of
United States Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991
in the aftermath of the Persian Gulf War. Because hundreds of oil well fires were
still burning, there was concern that ground troops stationed in Kuwait might be
exposed to high levels of PAHs and other toxicants. The United States Army
Environmental Hygiene Agency monitored air and soil for ambient PAHs. In
addition, a group of 61 soldiers was involved in the biomonitoring study reported
here. These soldiers kept diaries of daily activities and provided blood and
urine samples in Germany (June) before deployment to Kuwait, after 8 weeks in
Kuwait (August), and 1 month after the return to Germany (October). Here we
present data for PAH-DNA adducts measured by immunoassay in blood cell DNA
samples obtained at all three sampling times from 22 soldiers and bulky aromatic
adducts measured by 32P-postlabeling in blood cell DNA samples from 20 of the
same soldiers. Urinary 1-hydroxypyrene-glucuronide levels were determined by
synchronous fluorescence spectrometry in a matched set of samples from 33
soldiers. Contrary to expectations, environmental monitoring showed low ambient
PAH levels in the areas where these soldiers were working in Kuwait. For both DNA
adduct assays, levels were the lowest in Kuwait in August and increased
significantly after the soldiers returned to Germany (October). Urinary 1
hydroxypyrene-glucuronide levels were also lowest in Kuwait and highest in
Germany, but the differences were not statistically significant. The PAH-exposure
biomarker levels were not significantly influenced by polymorphic variations of
CYP1A1 (MspI) and glutathione S-transferases M1 and T1. Overall, the data suggest
that this group of soldiers was not exposed to elevated levels of PAHs while
deployed in Kuwait.
PMID- 9641501
TI - Genetic polymorphisms in glutathione S-transferase mu and theta, N
acetyltransferase, and CYP1A1 and risk of gliomas.
AB - The role of genetic polymorphisms in modulating susceptibility to carcinogenic
exposures has been well explored for tobacco-related neoplasms but not for other
neoplasms including gliomas. It is relevant to explore these polymorphisms
because certain carcinogenic exposures such as nitrosamines are implicated in the
risk of gliomas. We therefore conducted a pilot case-control study to examine the
role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow
acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with
glioma were ascertained as part of an ongoing genetic epidemiological study and
were age, gender, and race matched with 90 healthy controls. We used PCR based
methodology to determine the prevalence of the above genetic polymorphisms using
sequences and PCR conditions directly adapted from studies reported previously.
We calculated univariate odds ratios and performed multiple logistic regression
to assess interactions between polymorphisms. We found no statistically
significant associations between the null genotypes of GSTM1 and GSTT1, and
CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2
acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate,
and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any
single polymorphism is sufficiently predictive of risk, and a panel of markers
integrated with epidemiological data should be conducted on a large number of
study subjects to fully understand the role of genetic polymorphisms and brain
tumor risk.
PMID- 9641502
TI - A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome:
clinical outcome and analysis of autoantibodies to serotonin, gangliosides and
phospholipids.
AB - The aim of the study was to evaluate in a double-blind manner the effect of the
long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical
symptoms in patients with fibromyalgia syndrome (FM) and on production of
antibodies to serotonin, gangliosides and phospholipids, recently shown to have a
high incidence in this disease. Fifty-one female patients with typical FM were
included in the 16-week study: 24 received Ritanserin and 27 received a placebo.
Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were
determined by enzyme-linked immunosorbent assay at day 0 and at the end of week
16. The psychological and physical status, including tender points, of the
patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of
the study, there was an improvement (p < 0.05) in feeling refreshed in the
morning in the Ritanserin-treated group and headache was also significantly
improved compared with the placebo group. There was no difference in pain,
fatigue, sleep, morning stiffness, anxiety and tender point counts in the
Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least
one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and
activity of these antibodies were not influenced by Ritanserin or placebo. The
observation that Ritanserin has only a small effect on clinical symptoms
indicates that disturbances in serotonin metabolism or uptake may be only one
factor in the pathogenesis of the disease. The high incidence of a defined
autoantibody pattern in FM could again be confirmed in this study. However, it
remains speculative whether immunological reactions are, indeed, involved.
PMID- 9641503
TI - Osteonecrosis of the tibial plateau.
AB - The clinical, radiographic and scintigraphic findings in 12 patients diagnosed
with osteonecrosis of the tibial plateau (10 of the medial and two of the lateral
plateau) were analysed. The disease presented suddenly in most of the patients,
as acute pain in the lateral side of the knee, with no major traumatic
antecedents. X-ray findings were varied and non-specific, and hence of little
value for initial diagnosis. On the other hand, scintigraphic findings were very
useful for diagnostic purposes in all cases. All the patients were over 55 years
of age and 11 out of 12 were women. The most frequent location of the disease was
the medial tibial plateau; however, two cases involved the lateral plateau and
two involved both plateaux. Seven patients were subjected to full knee
arthroplasty, four to valgising osteotomy and one to grafting. The patients'
diagnoses were considerably delayed (by more than 6 months), which affected their
treatment and prognosis.
PMID- 9641504
TI - Chondrocyte phenotyping in human osteoarthritis.
AB - Cell-ECM (extracellular matrix) interactions are believed to play a key role in
maintaining the normal structure of tissues such as cartilage. Cell surface
adhesion molecules have been reported to mediate chondrocyte binding to ECM
proteins in human normal cartilage but the behaviour of these molecules in human
osteoarthritic cartilage is unknown. We studied receptor matrix proteins on
freshly isolated chondrocytes obtained from 10 patients with osteoarthritis (OA).
Chondrocytes were isolated by enzymatic digestion from three zones of the
articular cartilage with a different degree of macroscopic and microscopic damage
and chondrocyte phenotype was defined by flow cytometry. Chondrocytes strongly
expressed beta1, integrin but not beta3 integrin. LFA-1 (CD18/CD11a) and ICAM-1
(CD54) antigens were almost undetectable. Interestingly, beta1 expression was
significantly higher in the minimally damaged zone than in the zones with medium
and maximum damage. These data show that beta1-integrin-mediated chondrocyte-ECM
interactions decrease in osteoarthritic cartilage suggesting that perturbations
of chondrocyte-matrix signalling occurs during OA.
PMID- 9641505
TI - HLA-DR gene frequencies in a Zairean population with particular reference to
rheumatic diseases.
AB - Epidemiological studies have shown that rheumatic diseases such as rheumatoid
arthritis and systemic lupus erythematosus are uncommon in black Africans, and in
this population the prevalence and the clinical features of these rheumatic
diseases are variable. Environmental and genetic factors have been pointed out to
explain this variability. In the present study, HLA-DR genes have been determined
in a Zairean population in order to compare our results with those found
elsewhere in other black populations of the same Bantu origin. Our results show
that the frequency of HLA-DR1 is higher than in Nigerians, Zimbabweans and
Xhosas, the decrease in Xhosas being statistically significant (p < 0.006). The
HLA-DR3 frequency is higher in Zaireans than in Nigerians but not significantly,
while it is lower than in Xhosas (p < 0.003) and in Zimbabweans (not
significant). The HLA-DR4 frequency is higher in Zaireans than in Nigerians but
it is lower than in Xhosas and Zimbabweans; the differences are not statistically
significant. The HLA-DR8 frequency is lower in Zaireans than in Nigerians while
it is higher than in Xhosas (p < 0.002) and in Zimbabweans (not significant).
These data suggest that genetic factors partly explain the clinical and
epidemiological variability of rheumatic diseases in black Africans.
PMID- 9641506
TI - Prolactin and interleukin-6 in neuropsychiatric lupus erythematosus.
AB - We investigated the levels of prolactin (PRL) and interleukin-6 (IL-6) in the
cerebrospinal fluid (CSF) and serum of systemic lupus erythematosus patients with
central nervous system involvement (CNS-SLE), and examined whether PRL and IL-6
have a relationship. Serum and CSF PRL and IL-6 were measured in the following
groups of patients and controls: group I: seven patients with CNS-SLE; group II:
three SLE patients without CNS involvement (non CNS-SLE); group III: 10 patients
with neurocysticercosis; and group IV: six healthy women. The patients were
clinically assessed. CSF PRL and IL-6 were elevated in group I (CNS-SLE) in
comparison with all other groups (p<0.001). In addition, four of seven patients
had higher levels of IL-6 and PRL in CSF than in serum. A positive correlation
between PRL and IL-6 in CSF of SLE was observed (r=0.88, p<0.001). The mean serum
PRL concentrations were not significantly different in all groups, but high
levels of IL-6 were found in the serum of group I in comparison with groups II
and IV (p<0.001). The serum levels of group III were not different from those of
group I. These results demonstrate the presence of intrathecal synthesis and
elevations of CSF PRL and IL-6 in active CNS-SLE involvement and indicate that
measurements of CSF PRL and IL-6 may be useful in the evaluation of
neuropsychiatric lupus erythematosus.
PMID- 9641507
TI - Systemic sclerosis stimulates angiogenesis in the chick embryo chorioallantoic
membrane.
AB - Skin biopsies from patients with systemic sclerosis (SSc) were investigated for
their angiogenic activity by using the chick embryo chorioallantoic membrane
(CAM) assay. Ten samples of SSc and 10 of normal skin from age- and sex-matched
subjects were grafted onto the CAM, and the angiogenic response in pathological
and control implants was assessed on histological sections by a planimetric point
count method 4 days after grafting. The vascular counts in the area underlying
the SSc were significantly higher than those of normal skin and a dense
mononuclear cell infiltrate was detectable around the blood vessels in
pathological specimens. These results suggest that SSc may promote angiogenesis,
perhaps leading to the release of several angiogenic factors. Moreover, the role
played in the angiogenic response by the inflammatory cells forming the cellular
infiltrate is suggested by this study.
PMID- 9641508
TI - HLA B27: a prognostic factor in juvenile chronic arthritis.
AB - This study was performed to assess the frequency of HLA B27 in patients with
juvenile chronic arthritis (JCA) of varying severity and outcome by studying
three patient categories: those in whom cytostatic treatment with azathioprine
had been started, those with secondary amyloidosis, and those with arthroplasty
of the knee or hip joints. In the first category the frequency of the HLA B27
allele was compared between those who had attained remission and those who had
not. In the second and third categories the rate at which amyloidosis developed
and the timing for the need of arthroplasty, were compared for HLA B27-positive
and -negative patients. A control group consisted of 37 patients with
uncomplicated seronegative polyarthritis. Ten of the 37 patients in the control
group (27%) were HLA B27 positive as opposed to 84 out of 190 (44%) in the three
study groups. Of the 101 patients treated with azathioprine, two out of 15 in
remission were HLA B27 positive, whereas as many as 41 out of 86 with still
active disease were HLA B27 positive (p = 0.013). Of the secondary amyloidosis
patients, 29 out of 51 carried HLA B27. The HLA B27-positive patients contracted
amyloidosis on average 5.9 (median 6.7) years earlier than the HLA B27-negative
patients (p = 0.038). Of the arthroplasty patients, 39 out of 91 carried HLA B27.
The HLA B27-positive patients underwent arthroplasty on average 2.9 (median 3.5)
years earlier than the HLA B27-negative patients (p = 0.050). We conclude that
HLA B27-positive cases are accumulated among the most severe cases of JCA.
PMID- 9641509
TI - A self-report Thompson articular index: what does it measure?
AB - The aim of this study was to investigate the reliability and validity of the self
report Thompson articular index (ThAI) in Dutch patients with rheumatoid
arthritis (RA). A rheumatologist assessed the ThAI in 43 patients with RA.
Patients completed the self-report ThAI and the AIMS-2 questionnaire to assess
physical function, pain, mood and level of tension. Blood samples were taken to
measure the erythrocyte sedimentation rate (ESR). After 4 weeks, patients were
sent a questionnaire for a repeat assessment of the self-report AI. The test
retest reliability of the self-report ThAI was adequate (ICC=0.83). There was low
agreement between ThAI scores from patients and AI scores assessed by the
rheumatologist (ICC=0.44). Self-report ThAI scores (mean=230.5) were
significantly higher than the rheumatologist's scores (mean=110.8). Levels of
agreement between patients and rheumatologist for individual joints were
disappointing, ranging from 49% to 74% (Cohen's kappa from -0.02 to 0.48). The
rheumatologist's ThAI scores correlated significantly with ESR (r=0.55) and
physical function (r=0.44), but not with pain, mood or level of tension.
Patients' scores correlated significantly with physical function (r=0.51), pain
(r=0.43), and mood (r=0.36) but not with ESR or level of tension. In regression
analyses the only significant predictor of the rheumatologist's ThAI scores was
ESR, and for patients' scores physical function, thus showing that patients'
responses are not confounded by mood or level of tension. In conclusion, the self
report ThAI is a reliable measure, but the validity is questionable because of
the non-significant correlation with ESR and the low level of agreement between
patients and rheumatologist. The results indicate that self-reported joint
involvement is more closely related to physical function than to arthritic
activity.
PMID- 9641510
TI - Outcomes for patients undergoing one or more total hip and knee arthroplasties.
AB - Either total hip arthroplasty (THA), total knee arthroplasty (TKA) or both were
performed in 105 patients from 1981 to 1994. These patients were experiencing
severe joint destruction in the lower extremities due to rheumatoid arthritis
(RA). These patients were followed for more than 2 years after their last
operation. Eighty-six patients were alive and 19 patients had died at the time of
follow-up. The 86 living patients were divided into four groups based on the
number of replaced joints. Their pre- and postoperative conditions, including
such factors as pain, mobility and disability for the quality of life (QOL), were
compared. All of the four groups showed some reduction in pain and disability,
and an improvement in ambulation after the operations. The 19 deceased patients
were classified into two groups, one including those with multiple (three or
four) arthroplasties and the other, those with only a small number (one or two).
The mean age at death was lower (55.7+/-6.2 years) in patients with multiple
arthroplasties than that (69.1+/-7.5 years) in patients with only a small number
of arthroplasties. Secondary diseases from RA, such as amyloidosis, spinal injury
and pulmonary fibrosis, were found to be the primary cause of death in patients
with multiple arthroplasties. The most important finding in this study is that
although RA patients with multiple arthroplasties in the lower extremities
improved their QOL, they were still afflicted with secondary diseases derived
from RA and experienced complications that could shorten their lifespan.
PMID- 9641511
TI - When does subluxation of the first carpometacarpal joint cause swan-neck
deformity of the thumb in rheumatoid arthritis: a 20-year follow-up study.
AB - The aim of our study was to assess the incidence of subluxation of the first
carpometacarpal joint (CMC I) and to evaluate which degree of subluxation
produces swan-neck deformity of the thumb in rheumatoid arthritis (RA) occurring
over 20 years. The hands of 83 rheumatoid factor (RF)-positive RA patients with
recent (< or = 6 months) arthritis were evaluated radiographically at onset and
at 1, 3, 8 and 15 years; 68 patients were evaluated at 20 years from entry.
Subluxation was assessed in millimetres and compared with the MCP-I angle
measurement to evaluate the thumb deformity. A statistical end-point analysis was
performed between two different grades of subluxation. Subluxation of 2-3 mm was
non-specific and only one third of these thumbs showed swan-neck deformity. At
the end-point, subluxation of > or = 4mm was present in 17% of the thumbs, 81% of
which had the swan-neck deformity; only five thumbs did not show this deformity,
but presented deformed and unstable MCP I and interphalangeal joints. The
frequency of swan-neck deformity was highly significantly (p < 0.0001) increased
in the thumbs with severe CMC I subluxation (> or = 4 mm) compared with lesser
subluxation (< 4 mm). When subluxation of the CMC I exceeds 4 mm, the swan-neck
deformity of the thumb is a common consequence. This deformity is often
progressive, and the hand function of such patients should be followed up
carefully, both clinically and radiographically.
PMID- 9641512
TI - Does the French general practitioner correctly investigate and treat
osteoporosis? Groupe Rhumatologique d'Etudes Cliniques de Midi-Pyrenees.
AB - In our region, more than half the patients with osteoporosis are investigated and
treated by general practitioners. We carried out two surveys to discover whether
the diagnosis and treatment of osteoporosis were correctly carried out by general
practitioners in the Midi-Pyrenees region. The first survey concerned 85 patients
who had been diagnosed with osteoporosis by their general practitioner. These
patients were being seen for the first time in a hospital or private practice
setting by a rheumatologist who completed a questionnaire based solely on the
history taken from the patient and the records in the patient's possession. For
the second survey, 200 general practitioners who had referred patients to the
rheumatology department were sent a questionnaire on their management of
osteoporosis. Fifty-two physicians completed and returned the questionnaire. More
than half the general practitioners started treatment of osteoporosis without
fractures on the basis of standard spinal X-rays where the radiologist suggested
bone mineral loss. The initial biological investigation was correctly carried out
by only 6% of physicians. Treatment was correctly prescribed in only 34% of cases
of osteoporosis with fractures, 50% of osteoporosis without fractures and 50% of
senile cortical osteoporosis.
PMID- 9641513
TI - Anti-transfer RNA antibodies in two patients with pulmonary fibrosis, Raynaud's
phenomenon and polyarthritis.
AB - Patient W.S. (a 61-year-old woman) and patient T.M. (a 41-year-old man) developed
recurrent fevers, polyarthritis, Raynaud's phenomenon and interstitial pulmonary
fibrosis without apparent polymyositis. From HeLa cell extracts, sera from both
patients immunoprecipitated all species of intact and deproteinised tRNAs. To
identify the antibody binding site more precisely, tRNAs transcribed in vitro
from cloned Escherichia coli tRNA genes and various mutants were prepared and
used as antigens for immunoprecipitation. When the TpsiC loop, or the D loop were
deleted, such mutants were not bound by both sera, suggesting that the D and
TpsiC loops were required for antibody binding. Abrogation of tRNA binding
occurred when 18G of tRNATrp was replaced with 18A to break the tertiary L-shape
structure of tRNA. These results strongly suggest that sera from W.S. and T.M.
recognise the tertiary conformation of L-shaped tRNA which is constructed with
both D and TpsiC loops. These autoantibodies may also serve as a marker for a new
subset of patients with connective tissue diseases that is distinct from anti
aminoacyl-tRNA synthetase syndrome.
PMID- 9641514
TI - Polyarthritis, rash and lymphadenopathy: case reports of two patients with
angioimmunoblastic lymphadenopathy presenting to a rheumatology clinic.
AB - Two patients presented with a symmetrical inflammatory polyarthropathy. Both
patients fulfilled the diagnostic criteria for angioimmunoblastic
lymphadenopathy. We present the two case histories and review the current
literature. Although an uncommon disease, the diagnosis of angioimmunoblastic
lymphadenopathy should be considered in a patient presenting with polyarthritis
and skin rash.
PMID- 9641515
TI - Tenosynovitis due to Mycobacterium avium intracellulare and Mycobacterium
chelonei: report of two cases with review of the literature.
AB - Atypical mycobacteria can induce soft tissue infections such as tenosynovitis. We
observed one case of finger flexor tendon tenosynovitis infected with
Mycobacterium avium intracellulare and one case of knee and ankle arthritis with
lateral peroneal tendon tenosynovitis due to M. chelonei. In the first patient, a
tenosynovectomy only was performed leading to resolution of the infection. The
second patient was immunocompromised as a result of corticosteroid therapy and
the mycobacterial infection was treated with tenosynovectomy and multidrug
chemotherapy. This patient died from infectious pneumonitis. Previously reported
cases of infectious tenosynovitis due to these atypical mycobacteria are
reviewed.
PMID- 9641516
TI - Flexion contractures associated with a malignant neoplasm: 'A paraneoplastic
syndrome?'.
AB - A 71-year-old man developed polyarthritis and, subsequently, severe flexion
contractures of multiple joints, particularly the joints of the hands. Eighteen
months after developing this disease a parailiacal lymph node metastasis of an
unknown primary cancer was found. We suggest that this patient's history,
dominated by contractures that resembled the 'palmar fasciitis and polyarthritis
syndrome', should be considered as a paraneoplastic syndrome.
PMID- 9641517
TI - Very low-dose cyclosporin treatment of steroid-resistant interstitial pneumonitis
associated with Sjogren's syndrome.
AB - Cyclosporin is known to be effective for both transplantation and a spectrum of
immune-mediated diseases. Because this agent also causes severe adverse effects,
especially nephrotoxicity, careful monitoring is required for the development of
such reactions. Here we report the successful treatment with extremely low-dose
cyclosporin (1 mg/kg/day) of a patient who had steroid-resistant interstitial
pneumonitis and Sjogren's syndrome.
PMID- 9641518
TI - Peripheral neuropathy associated with temporal arteritis.
AB - Peripheral neuropathy is described in a patient with biopsy proven giant cell
arteritis. Sural nerve biopsy showed myelin and axonal degeneration. Such an
uncommon manifestation was resolved with corticosteroid therapy.
PMID- 9641519
TI - Granulomatous tenosynovitis: a rare musculoskeletal manifestation of
tuberculosis.
AB - A patient with tenosynovial tuberculosis affecting the extensor tendons of the
wrist and hand is presented. This case highlights the clinical and magnetic
resonance features of tuberculous tenosynovitis, and seeks to increase awareness
of what may represent a resurgent musculoskeletal entity.
PMID- 9641520
TI - Rotator cuff tear associated with an acromioclavicular cyst in rheumatoid
arthritis.
AB - We report two cases of a full-thickness rotator cuff tear followed by
acromioclavicular cyst formation in patients with longstanding erosive
polyarticular rheumatoid arthritis. One of the consequences of a rotator cuff
tear is articular instability with upward migration of the humeral head. The
ensuing chronic friction against the undersurface of the acromioclavicular joint
caused by arm movements can lead to a non-inflammatory effusion of the
acromioclavicular joint with cyst formation. Clinical and ultrasonographic
features and a pathogenetic hypothesis are discussed.
PMID- 9641521
TI - Buschke-Ollendorff syndrome in a grande multipara: a case report and short review
of the literature.
AB - A 36-year-old short-statured grande multipara (gravida 10, para 8) with diabetes
mellitus and hyperlipidaemia was incidentally found to have Buschke-Ollendorff
syndrome (osteopoikilosis and dermatofibrosis lenticularis disseminata). The
pelvis and hips, followed by the knees, were the sites mainly affected by the
osteopoikilosis. The lumbosacral spine was also affected. She had a single
connective tissue naevus on the right thigh. Apart from two abortions, the
repeated pregnancies were uneventful and all her deliveries were normal at full
term or nearly full-term. With regard to the relationship between Buschke
Ollendorff syndrome and multiparity, it was apparent that multiparity did not
affect the involved weight bearing bony structures, nor did the disseminated
osteopoikilosis interfere with the endurance of multiple pregnancies. Buschke
Ollendorff syndrome is known generally to have a benign course, a feature that is
illustrated in this case, even when associated with the stresses of multiparity.
The report also provides a short and updated review of various clinical aspects
of the syndrome and its associations, some of which are of a serious nature.
PMID- 9641522
TI - Superior vena cava syndrome together with multiple venous thrombosis in Behcet's
disease.
AB - In this paper, we describe a 25-year-old white man with Behcet's disease who
developed superior vena cava syndrome which was followed with the diagnosis of
pseudotumour cerebri based on bilateral papilledema for 6 months. Complete
superior vena cava obstruction was detected by magnetic resonance imaging (MRI).
Secondary reasons for papilledema were all excluded. Treatment of prednisone,
pulse cyclophosphamide and heparin was started and clinical symptoms and
fundoscopic changes completely disappeared in 2 weeks. In conclusion, we think
that Behcet's disease should always be remembered in the differential diagnosis
of unidentified neurological signs especially in regions where the disease is
relatively common.
PMID- 9641523
TI - Amino acid transport in cerebral microvessels during Plasmodium yoelii infection
in mice.
AB - Plasmodium yoelii infected cerebral microvessels of mice had an enhanced time
dependent, temperature-sensitive, and saturable uptake of [14C]-amino acid. viz.
leucine, valine and glycine. Metabolic inhibitors caused a noticeable inhibition
of amino acid uptake in normal microvessels as compared to infected cerebral
microvessels indicating that the uptake of [14C]-L-leucine, [14C]-L-valine and
[14C]-glycine is an energy dependent process.
PMID- 9641524
TI - Developmental expression of nitric oxide synthase in the rat diencephalon with
special reference to the thalamic paratenial nucleus.
AB - Using immunohistochemistry and in situ hybridization the distribution of nitric
oxide synthase (NOS) was investigated in the rat brain during pre- and postnatal
development. At E15 weak NOS-like immunoreactivity (NOS-LI) could be seen in the
differentiation field of the anterior hypothalamus. At E17 strong NOS-LI was
observed in the developing neurons of the hypothalamic paraventricular nucleus,
supraoptic nucleus, anterodorsal nucleus and lateral hypothalamic areas. In the
thalamic paratenial nucleus a strong NOS-LI was observed in these neurons at E17,
E18 and P1 with a weaker intensity at P3, P7, P9 and P15, whereas at P30 and in
adult rats no NOS-positive neurons could be detected. NOS expression at E17 and
P3 was verified by in situ hybridization. These results suggest that NO may have
a developmental role at least in one of the regions studied, the thalamic
paratenial nucleus.
PMID- 9641526
TI - Expression of GABA(A) receptors by reactive astrocytes in explant and primary
cultures of rat CNS.
AB - The presence of GABA(A)-receptors on astrocytes was studied in explant and
primary cultures of rat cerebellum, hippocampus and spinal cord by means of
immunohistochemistry. For these studies we have used the monoclonal antibody bd
17 against the beta2- and beta3-subunits of GABA(A)-receptor. In explant cultures
many neurones were intensely stained with the GABA(A)-receptor antibody whereas
adjacent astrocytes revealed little or no immunoreactivity. In the far outgrowth
zone of explant culture, however, many immunostained astrocytes were observed. In
primary astrocyte cultures, only a few cells were stained by the antibody.
Astrocytes which became reactive after producing an artificial scar or after
addition of certain compounds such as dibutyryl cyclic AMP, interleukin-6, basic
fibroblast growth factor and kainic acid, also revealed GABA(A)-receptor
immunoreactivity. Furthermore, these astrocytes were intensely stained for glial
fibrillary acidic protein and vimentin. From our studies we conclude that only a
sub-population of normal astrocytes are immunopositive for the GABA(A)-receptor
antibody whereas astrocytes which become reactive following injury of the tissue
or after addition of dibutyryl cyclic AMP, the cytokine interleukin-6, fibroblast
growth factor or the neurotoxin kainic acid express GABA(A)-sites.
PMID- 9641525
TI - Alterations in the activities of cerebral antioxidant enzymes of rat are related
to aging.
AB - Developmental profiles of antioxidant enzymes and lipid peroxidation were
investigated in rat cerebral hemisphere from birth to 600 days of age. Lipid
peroxidation level decreased in the crude homogenate from birth until 15 days
and, thereafter increased gradually up to 600 days. However, susceptibility of
sub-cellular fractions to lipid peroxidation displayed an increasing trend with
increasing age. Superoxide dismutase activity decreased gradually with age,
whereas activities of catalase, glutathione peroxidase and glutathione reductase
exhibited an elevation up to 90 days followed by either a stagnancy or diminution
in the later life. No linearity was observed in the contents of glutathione,
ascorbic acid and H2O2 in the tissue. The results suggest that free radicals
could be the causative agents of the aging process in which antioxidant enzymes
have a definite regulatory contribution.
PMID- 9641527
TI - Effects of oxidative stress on prion protein expression in PC12 cells.
AB - PC12 cells are known to express the prion protein, a normal cell surface
glycoprotein. This protein is upregulated in PC12 cells differentiated with nerve
growth factor. A neurotoxic prion protein peptide, PrP106-126, is not toxic to
PC12 cells alone. PrP106-126 is toxic to PC12 cells co-cultured with microglia
and more so to NGF-differentiated PC12 cells. PC12 cells selected for resistance
to either copper toxicity or oxidative stress have higher levels of PrP(C)
expression. Both PC12 variants are more sensitive to the toxicity of PrP106-126.
This suggests that PC12 sensitivity to PrP106-126 toxicity is related to prion
protein expression and not to a state of high differentiation induced by NGF.
Variants of PC12 cells that are more resistant to copper toxicity have higher
levels of anti-oxidant enzymes, superoxide dismutase and glutathione peroxidase.
Our results suggest that cells expressing higher levels of PrP(C) have higher
resistance to oxidative stress or copper toxicity but are more sensitive to
PrP106-126 toxicity. Prion protein expression may be involved in both the
metabolism of copper and resistance to oxidative stress. Increased cellular
resistance to copper toxicity may be partly related to increased activity of anti
oxidant enzymes.
PMID- 9641528
TI - The effects of TGF-beta1 on chick embryo retina development in vitro.
AB - This paper studies the effect exerted by TGF-beta1 on the development of chick
embryo retina cultured in vitro. The addition of TGF-beta1 to retinal explants
inhibited DNA synthesis, measured as 3H-thymidine incorporation into
trichloroacetic acid-insoluble fraction, while it increased both wet weight and
protein content, in particular that of extracellular matrix proteins. Lastly, in
explants treated with TGF-beta1 an increment in the level of fibronectin was
demonstrated by means of Western blotting analysis.
PMID- 9641529
TI - Brain-derived neurotrophic factor gene expression in the developing zebrafish.
AB - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family
of polypeptides that includes NGF, NT-3, NT-4/5 and NT-6. Although neurotrophins
are known to be expressed in teleost fishes little is known about their functions
in the development of these vertebrates. We are therefore studying BDNF in the
zebrafish, Danio rerio. The structure of zebrafish BDNF mRNA was established
using PCR and cDNA cloning. The encoded BDNF was 91% identical to mammalian BDNF.
Southern blot analysis revealed a unique BDNF gene. Northern blot analysis
detected two heterogeneous populations of BDNF transcripts centered at 1.6 and 2
kb. BDNF transcripts were first measurable 24 h post-fertilization (pf). Their
abundance relative to total transcripts increased 6-fold between 1 day and 3 days
pf and again 2-fold by 7 days pf. In situ hybridization analyses of 4-day-old
larvae revealed BDNF transcripts in the retina, brain, otic vesicle, pectoral fin
and the hair cells of the neuromast. The early onset and cellular sites of
expression suggest that BDNF functions in nervous system and fin development in
the zebrafish.
PMID- 9641530
TI - Visual perception: myths and mechanisms.
PMID- 9641531
TI - Mathematical guidance for axons.
AB - Axon guidance by gradients plays an important role in wiring up the developing
nervous system. Growth cones seem to sense a concentration difference across
their spatial extent, and convert this into a signal to move up or down a
gradient. In this article, a simple mathematical framework is developed to
understand when and where gradient detection can occur as a function of gradient
shape. This framework is applied to two examples:the guidance of axons by target
derived diffusible factors in vivo and in collagen gels, and guidance by
substrate-bound gradients of optimal shape, as might be relevant in the
retinotectal system.Two distinct spatial limits on guidance emerge: I mm for a
target-derived diffusible gradient, and I cm for a substrate-bound gradient.
PMID- 9641532
TI - Simulation in neurobiology: theory or experiment?
AB - Investigation in neurophysiology usually involves measurements of large
population-average signals or small sample recordings. There is an underlying
assumption that the observations express activity of large groups of similarly
acting neurons that is the result of a bottom-up scenario in which individual
cells, via their synaptic interactions, lead to the large scale phenomena. The
connection between the levels must be provided by theory, which must also provide
the relevant variables for observation. It is suggested that between the
experiment and the full theory there is a creative, mixed role for simulation:
both experimental and theoretical. A simulation presents complex dynamics and
hence is an empirical board for testing theoretical tools, yet its controlled
behaviour can make predictions about the biological system.
PMID- 9641533
TI - Rembrandt's 'The anatomy lesson of Dr. Joan Deijman'.
AB - Rembrandt's striking painting of a human brain being dissected by a headless
figure is actually a fragment of a larger work. The original was both a
commissioned group portrait of a surgeons' guild and an account of a public
dissection. Such dissections served both educational and entertainment functions
in 17th century Holland.
PMID- 9641534
TI - Intrinsic circuitry of the amygdaloid complex: common principles of organization
in rats and cats.
PMID- 9641535
TI - The GluR2 (GluRB) hypothesis in ischemia: missing links.
PMID- 9641536
TI - New insights into the regulation and function of brain estrogen synthase
(aromatase).
AB - In the brain, conversion of androgens into estrogens by the enzyme aromatase
(estrogen synthase) is a key mechanism by which testosterone regulates many
physiological and behavioral processes, including the activation of male sexual
behavior, brain sexual differentiation and negative feedback effects of steroid
hormones on gonadotropin secretion. Studies on the distribution and regulation of
brain aromatase have led to a new perspective on the control and function of this
enzyme. A growing body of evidence indicates that the estrogen regulation of
aromatase is, at least in part, trans-synaptic. Afferent catecholamine pathways
appear to regulate aromatase activity in some brain areas and thereby provide a
way for environmental cues to modulate this enzyme. The localization of aromatase
in pre-synaptic boutons suggests possible roles for estrogens at the synapse.
PMID- 9641537
TI - The synucleins: a family of proteins involved in synaptic function, plasticity,
neurodegeneration and disease.
AB - Synuclein proteins are produced, in vertebrates, by three genes. They share
structural resemblance to apolipoproteins, but are abundant in the neuronal
cytosol and present in enriched amounts at presynaptic terminals. Synucleins have
been specifically implicated in three diseases:Alzheimer's (AD), Parkinson's (PD)
and breast cancer. In AD, a peptide derived from alpha-synuclein forms an
intrinsic component of plaque amyloid. In PD, an alpha-synuclein allele is
genetically linked to several independent familial cases, and the protein appears
to accumulate in Lewy bodies. In breast cancer, increased expression of gamma
synuclein correlates with disease progression. In songbirds, alpha-synuclein
expression is correlated with plasticity in the developing song control system.
Although the normal function of synucleins is unknown, a role in membrane
plasticity seems likely.
PMID- 9641538
TI - Is there a vestibular cortex?
AB - Very different areas of the primate cortex have been labelled as 'vestibular'.
However, no clear concept has emerged as to where and how the vestibular
information is processed in the cerebral cortex. On the basis of data from single
unit recordings and tracer studies, the present article gives statistical
evidence of the existence of a well-defined vestibular cortical system. Because
the data presented here have been verified in three different primate species, it
can be predicted that a similar vestibular cortical system also exists in humans.
PMID- 9641539
TI - The 'Ideal Homunculus': decoding neural population signals.
AB - Information processing in the nervous system involves the activity of large
populations of neurons. It is possible, however, to interpret the activity of
relatively small numbers of cells in terms of meaningful aspects of the
environment. 'Bayesian inference' provides a systematic and effective method of
combining information from multiple cells to accomplish this. It is not a model
of a neural mechanism (neither are alternative methods, such as the population
vector approach) but a tool for analysing neural signals. It does not require
difficult assumptions about the nature of the dimensions underlying cell
selectivity, about the distribution and tuning of cell responses or about the way
in which information is transmitted and processed. It can be applied to any
parameter of neural activity (for example, firing rate or temporal pattern). In
this review, we demonstrate the power of Bayesian analysis using examples of
visual responses of neurons in primary visual and temporal cortices. We show that
interaction between correlation in mean responses to different stimuli (signal)
and correlation in response variability within stimuli (noise) can lead to marked
improvement of stimulus discrimination using population responses.
PMID- 9641540
TI - Development of whisker-related patterns in marsupials: factors controlling
timing.
AB - In mature rodents, whisker-related patterns are known to be present in three
levels of the brain: the brainstem trigeminal nuclei, the ventrobasal thalamus
and the somatosensory cortex. These patterns have been demonstrated using
neuroanatomical tracing techniques, histological and histochemical staining
methods and electrophysiological recordings. The development and topography of
these patterns are dependent on an intact periphery. But what governs when
patterns form at the three levels? Possibilities include a controlling signal
from the periphery or local mechanisms at each site, such as the arrival of
afferent inputs or the maturation of target tissue. In this review, we report on
the maturation of the whisker pathway in a marsupial, the wallaby, where the slow
tempo of development is a feature. At each level, afferent fibres grow into the
region of termination many weeks before the whisker-related pattern emerges. The
results suggest that the maturity of the target tissue as well as signals from
the periphery combine to trigger pattern formation at each level of the pathway.
PMID- 9641541
TI - Bladder distension and activation of the efferent function of sensory fibres:
similarities with the effect of capsaicin.
AB - 1. The effects of the tachykinin NK2 receptor antagonist MEN 11420 (100 nmol kg(
1), i.v.) and isoprenaline (400 nmol kg(-1), i.v.) were compared in a model of
distension-induced bladder activity in isovolumetric conditions. MEN 11420
induced a relaxation of the basal tone of the urinary bladder that was dependent
on the volume of the viscus: the effect was absent at low volumes (0.2 and 0.5
ml) and it was maximal at high volumes of distension (1 and 2 ml), approaching
about 60% of the isoprenaline-induced relaxation. The relaxant effect of
isoprenaline was always evident at all volumes of distension. 2. Tetrodotoxin (1
100 microM, intravesically applied) abolished distension-evoked micturition
contractions, but did not prevent the relaxant effect of MEN 11420- or
isoprenaline on the bladder tone. 3. The cyclo-oxygenase inhibitor S-ketoprofen
(0.5 micromol kg(-1), i.v.) produced a marked decrease of the bladder tone and a
concomitant reduction of bladder motility at 1 ml volume of distension. At 2 ml
of distension, S-ketoprofen still decreased the minimal pressure but had no
significant effect on other parameters of vesical motility. In S-ketoprofen
pretreated rats, the relaxant effect of MEN 11420 was significant at 2 but not at
1 ml of distension, and that of isoprenaline was reduced by 50% at both 1 and 2
ml. 4. Ruthenium red (10 micromol kg(-1), i.v.) had no effect at a low volume of
distension (0.2 ml) or at highest volume (2 ml) but decreased the basal tone and
the frequency of bladder contractions at 1 ml of distension. In ruthenium red
pretreated rats, MEN 11420 failed to decrease bladder tone at 1 ml, whereas at 2
ml the effect of MEN 11420 was not different from that observed in controls (43
vs 60% of isoprenaline-induced relaxation, respectively). 5. At both 1 and 2 ml
of distension, capsaicin pretreatment (164 micromol kg(-1), s.c. 5 days before)
reduced the frequency of micturition contractions but had no effect on the
bladder tone. Capsaicin pretreatment prevented the relaxant effect of MEN 11420
on the bladder tone both at 1 and at 2 ml of distension. 6. It is concluded that
the release of tachykinins from capsaicin-sensitive afferent nerves induced by
bladder distension is resistant to tetrodotoxin and to prostaglandin synthesis
inhibition. Tachykinins modulate the vesical tone by acting through NK2
receptors.
PMID- 9641542
TI - Effects of tachykinin NK1 receptor antagonists on vagal hyperreactivity and
neuronal M2 muscarinic receptor function in antigen challenged guinea-pigs.
AB - 1. The role of tachykinin NK1 receptors in the recruitment of eosinophils to
airway nerves, loss of inhibitory neuronal M2 muscarinic receptor function and
the development of vagal hyperreactivity was tested in antigen-challenged guinea
pigs. 2. In anaesthetized guinea-pigs, the muscarinic agonist, pilocarpine (1-100
microg kg(-1), i.v.), inhibited vagally induced bronchoconstriction, in control,
but not in antigen-challenged guinea-pigs 24 h after antigen challenge. This
indicates normal function of neuronal M2 muscarinic receptors in controls and
loss of neuronal M2 receptor function in challenged guinea-pigs. Pretreatment of
sensitized guinea-pigs with the NK1 receptor antagonists CP99994 (4 mg kg(-1),
i.p.), SR140333 (1 mg kg(-1), s.c.) or CP96345 (15 mg kg(-1), i.p.) before
antigen challenge, prevented M2 receptor dysfunction. 3. Neither administration
of the NK1 antagonists after antigen challenge, nor pretreatment with an NK2
receptor antagonist, MEN10376 (5 micromol kg(-1), i.p.), before antigen
challenge, prevented M2 receptor dysfunction. 4. Electrical stimulation of the
vagus nerves caused a frequency-dependent (2-15 Hz, 10 V, 0.2 ms for 5 s)
bronchoconstriction that was significantly increased following antigen challenge.
Pretreatment with the NK1 receptor antagonists CP99994 or SR140333 before
challenge prevented this increase. 5. Histamine (1-20 nmol kg(-1), i.v.) caused a
dose-dependent bronchoconstriction, which was vagally mediated, and was
significantly increased in antigen challenged guinea-pigs compared to controls.
Pretreatment of sensitized animals with CP99994 before challenge prevented the
increase in histamine-induced reactivity. 6. Bronchoalveolar lavage and
histological studies showed that after antigen challenge significant numbers of
eosinophils accumulated in the airways and around airway nerves. This
eosinophilia was not altered by pretreatment with the NK1 receptor antagonist
CP99994. 7. These data indicate that pretreatment of antigen-sensitized guinea
pigs with NK1, but not with NK2 receptor antagonists before antigen challenge
prevented the development of hyperreactivity by protecting neuronal M2 receptor
function. NK1 receptor antagonists do not inhibit eosinophil accumulation around
airway nerves.
PMID- 9641543
TI - Effects of pravastatin on cholesterol metabolism of cholesterol-fed heterozygous
WHHL rabbits.
AB - 1. We administered the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
pravastatin at a daily dose of 1 mg kg(-1) body weight to cholesterol-fed (0.03%)
heterozygous Watanabe heritable hyperlipidaemic rabbits, an animal model for
heterozygous familial hypercholesterolaemia. 2. After 12 months of cholesterol
treatment, immunohistochemistry with the monoclonal antibody 9D9 was used to
detect hepatic low density lipoprotein (LDL) receptors, which were quantified by
densitometry. In addition we determined LDL receptor mRNA by competitive reverse
transcriptase polymerase chain reaction. The cholesterol precursor lathosterol
and the plant sterol campesterol were analysed by gas-liquid chromatography. 3.
The drug reduced total plasma cholesterol levels by 51% (P=0.04), when compared
to the control group. Unexpectedly, hepatic LDL receptor density and mRNA showed
no significant differences between the groups. Total plasma levels of lathosterol
and campesterol also revealed no significant differences between the groups, if
expressed relative to plasma cholesterol. 4. The findings suggest that mechanisms
other than induced hepatic LDL receptors are responsible for the cholesterol
lowering effect of pravastatin in this animal model. We propose a reduced
cholesterol absorption efficiency compatible with similar campesterol levels
between both groups observed in our study.
PMID- 9641544
TI - G-protein activation at 5-HT1A receptors by the 5-ht1F ligand LY334370 in guinea
pig brain sections and recombinant cell lines.
AB - 1. G-protein activation by the 5-ht1F receptor agonist 5-(4-fluorobenzoyl)amino-3
(1-methylpiperidin-4-yl)-1H-indole fumarate (LY334370) was investigated by use of
autoradiography of receptor-activated G-proteins in guinea-pig brain sections and
[35S]-GTPgammaS binding responses in cell lines stably expressing human 5-HT1A (h
5-HT1A) receptors. 2. LY334370 (10 microM) caused little or no stimulation of
[35S]-GTPgammaS binding in guinea-pig brain regions enriched in 5-ht1F binding
sites (e.g., claustrum, caudate/putamen and thalamic nuclei), as identified by
labelling with 10 nM [3H]-sumatriptan plus 10 nM 5-carboxamidotryptamine (5-CT).
3. Application of LY334370 (10 microM) to guinea-pig brain sections resulted in
an increase of [35S]-GTPgammaS binding in hippocampus (123+/-17%), lateral septum
(58+/-14%), dorsal raphe (57+/-10%), entorhinal (37+/-11%) and cingulate cortex
(28+/-10%). This distribution fits with the G-protein activation mediated by 5
HT1A receptors as found with lisuride (10 microM), and labelling of 5-HT1A
receptors by 140 pM [125I]-4-(2'-methoxy-phenyl)- -[2'-(n-2"-pyridinyl)-p
iodobenzamido]-ethyl-piperazine (p-MPPI). 4. The LY334370-mediated [35S]
GTPgammaS response was antagonized by the selective, silent 5-HT1A receptor
antagonist N-[2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohex
anecarboxa-mide (WAY100635, 1 microM) in each of the brain structures
investigated. The distribution pattern of the [35S]-GTPgammaS binding response
and the antagonist profile suggest that the LY334370-induced response in guinea
pig brain is mediated by 5-HT1A receptors. 5. The maximal LY334370-induced [35S]
GTPgammaS binding response (83 to 94%) in membranes of recombinant C6-glial/h 5
HT1A and HeLa/h 5-HT1A cells was close to that of 5-HT, suggesting LY334370 to
exert high intrinsic activity at h 5-HT1A receptors. 6. In conclusion, in guinea
pig brain sections and recombinant cell lines the 5-ht1F receptor agonist
LY334370 causes G-protein activation that is mediated by 5-HT1A receptors.
Caution should be taken when employing this ligand as a putative selective 5-ht1F
agonist.
PMID- 9641545
TI - Modulation of angiotensin-converting enzyme by nitric oxide.
AB - 1. The aim of the present study was to determine the effect of nitric oxide (NO)
on angiotensin-converting enzyme (ACE) activity. 2. A biochemical study was
performed in order to analyse the effect of the NO-donors, SIN-1 and
diethylamine/NO (DEA/NO), and of an aqueous solution of nitric oxide on the ACE
activity in plasma from 3-month old male Sprague-Dawley rats and on ACE purified
from rabbit lung. SIN-1 significantly inhibited the activity of both enzymes in a
concentration-dependent way between 1 and 100 microM. DEA/NO inhibited the
activity of purified ACE from 0.1 microM to 10 microM and plasma ACE, with a
lower potency, between 1 and 100 microM. An aqueous solution of NO (100 and 150
microM) also inhibited significantly the activity of both enzymes. Lineweaver
Burk plots indicated an apparent competitive inhibition of Hip-His-Leu hydrolysis
by NO-donors. 3. Modulation of ACE activity by NO was also assessed in the rat
carotid artery by comparing contractions elicited by angiotensin I (AI) and AII.
Concentration-response curves to both peptides were performed in arteries with
endothelium in the presence of the guanylyl cyclase inhibitor, ODQ (10 microM),
and the inhibitor of NO formation, L-NAME (0.1 mM). NO, which is still released
from endothelium in the presence of 10 microM ODQ, elicited a significant
inhibition of AI contractions at low concentrations (1 and 5 nM). In the absence
of endothelium, 1 microM SIN-1 plus 10 microM ODQ, as well as 10 microM DEA/NO
plus 10 microM ODQ induced a significant inhibition on AI-induced contractions at
1 and 5 nM and at 1-100 nM, respectively. 4. In conclusion, we demonstrated that
(i) NO and NO-releasing compounds inhibit ACE activity in a concentration
dependent and competitive way and that (ii) NO release from endothelium
physiologically reduces conversion of AI to AII.
PMID- 9641546
TI - The contribution of nitric oxide to cardiovascular status and responses to
vasodilators in conscious, hypertensive, transgenic ((mRen-2)27) rats.
AB - 1. The aim of the study was to measure the regional haemodynamic responses to
vasodilators, and the effects of nitric oxide (NO) synthase inhibition, in
conscious, hypertensive, transgenic ((mRen-2)27) rats (TG rats) and normotensive,
Hannover Sprague-Dawley (SD) rats. 2. The hypotensive response to acetylcholine
was greater in TG than in SD rats, but the renal vasodilator responses were not
different. 3. The responses to bradykinin were similar in the two strains, except
that hindquarters vasodilatation occurred only in SD rats. 4. Salbutamol caused
smaller renal and hindquarters vasodilatation in TG rats than in SD rats, and
there was mesenteric vasodilatation only in the latter strain. 5. The hypotensive
response to sodium nitroprusside was smaller, but the accompanying mesenteric
vasodilatation was greater, in SD than in TG rats. 6. The contribution of NO to
the vasodilator responses was taken as the difference between the responses in
the presence of the NO synthase inhibitor, NG-nitro-L-arginine methylester (L
NAME), compared to those in the presence of a co-infusion of angiotensin II and
vasopressin (to match the haemodynamic effects of L-NAME). 7. In TG rats, L-NAME
caused a greater absolute pressor effect, but a smaller mesenteric
vasoconstriction, than in SD rats. 8. L-NAME affected the vasodilator responses
to all the challenges similarly in the two strains. 9. Collectively, the results
provide no direct evidence for impaired NO-mediated vasodilator mechanisms in TG
rats. It is feasible that the reduced hindquarters response to bradykinin and the
reduced renal and hindquarters responses to salbutamol, in TG rats are due to
abnormal beta2-adrenoceptor-mediated processes.
PMID- 9641547
TI - Effect of inhibition of tyrosine phosphatases on voltage-operated calcium channel
currents in rabbit isolated ear artery cells.
AB - 1. The effect of increasing cellular tyrosine phosphorylation by inhibiting
endogenous tyrosine phosphatases was examined on voltage-operated calcium channel
currents in vascular smooth muscle cells. 2. In single ear artery smooth muscle
cells of the rabbit, studied by the whole cell voltage clamp technique,
intracellular application of the tyrosine phosphatase inhibitors, sodium
orthovanadate (100 microM) and peroxyvanadate (100 microM orthovanadate + 1 mM
H2O2) increased voltage-operated calcium channel currents by 56% and 83%,
respectively. 3. Bath application of two other membrane permeant tyrosine
phosphatase inhibitors, phenylarsine oxide (100 microM) and dephostatin (50
microM) also increased voltage-operated calcium channel currents by 48% and 52%,
respectively. 4. The selective tyrosine kinase inhibitor, tyrphostin-23 (100
microM) reduced calcium channel currents by 41%. Pre-incubation with tyrphostin
23 abolished the effects of peroxyvanadate, phenylarsine oxide and dephostatin on
calcium channels. 5. Western blot analysis of rabbit ear artery cell lysates
showed increased tyrosine phosphorylation of several endogenous proteins
following treatment with peroxyvanadate. 6. These results indicate that a number
of structurally dissimilar inhibitors of tyrosine phosphatases increase voltage
operated calcium channel currents in arterial smooth muscle cells presumably due
to increased tyrosine phosphorylation.
PMID- 9641549
TI - Differential effects of somatostatin and angiopeptin on cell proliferation.
AB - 1. Somatostatin (SRIF) exerts antiproliferative effects, and angiopeptin (an
sst2/sst5 receptor-selective analogue) has recently been evaluated in clinical
trials for the prophylaxis of restenosis following coronary angioplasty. Using an
in vitro model of cell growth we have examined the effects of SRIF and
angiopeptin on cell proliferation in CHO-K1 cells stably transfected with the
human or rat recombinant sst2 or sst5 receptor and compared these with their
effects on rat aortic vascular smooth muscle cells (VSMC) expressing endogenous
somatostatin receptors. 2. In CHO-KI cells, expressing either human or rat
recombinant sst2 or sst5 receptors, or in rat aortic VSMC, SRIF and angiopeptin
(0.1-1000 nM) had no effect on basal re-growth of cells into a denuded area of a
previously confluent monolayer. In contrast, basic fibroblast growth factor
(bFGF, 10 ng ml(-1)) stimulated re-growth of these cells. 3. SRIF (0.1-1000 nM)
caused a concentration-dependent inhibition of the bFGF-stimulated re-growth in
CHO-K1 cells expressing human sst2 (h sst2) or sst5 (h sst5) receptors
(pIC50=8.05+/-0.03 and 8.56+/-0.12, respectively). In contrast, angiopeptin (0.1
1000 nM) acted as a partial agonist at the h sst2 receptor (44.6+/-2.7%
inhibition of the bFGF-stimulated re-growth at 100 nM; pIC50=8.69+/-0.25) but was
devoid of any agonist activity at the h sst5 receptor. 4. In CHO-K1 cells stably
expressing rat recombinant sst2 (r sst2) or sst5 (r sst5) receptors, SRIF (0.1
1000 nM) was able to inhibit the bFGF-stimulated re-growth (pIC50=7.98+/-24 and
8.50+/-0.12, respectively). Angiopeptin (0.1-1000 nM) caused a concentration
dependent inhibition of bFGF-stimulated re-growth at the r sst2 receptor
(pIC50=8.08+/-0.24) but acted as a partial agonist at the r sst5 receptor
(maximum response= 57.7+/-3.6% inhibition of bFGF-stimulated re-growth at 100 nM;
pIC50=8.60+/-0.16). 5. Although angiopeptin was inactive as an agonist at the h
sst5 receptor, 100 nM angiopeptin potently antagonized the SRIF-induced
inhibition of proliferation in CHO h sst5 (estimated pKB= 10.4+/-0.3). 5
Hydroxytryptamine (0.1 nM-10 microM) also inhibited bFGF-stimulated re-growth
(pIC50=8.36+/-0.11) and angiopeptin had no effect on this response (pKB<7). 6.
SRIF (0.1-1000 nM) caused a concentration-dependent (pIC50=8.04+/-0.08)
inhibition of bFGF-stimulated re-growth in VSMC, whereas angiopeptin displayed
weak agonist activity, only inhibiting bFGF-stimulated re-growth at
concentrations greater than 100 nM. Angiopeptin (100 nM) caused a rightward
displacement of the concentration-effect curve to SRIF with an estimated pKB
value of 7.70+/-0.12. 7. These findings suggest that the low intrinsic activity
of angiopeptin at the h sst2 receptor, combined with its lack of agonist activity
at the h sst5 receptor, may explain the poor clinical efficacy of angiopeptin in
trials for coronary artery restenosis, which contrasts with encouraging data
found in equivalent in vivo animal studies.
PMID- 9641548
TI - Modulation of extracellular GABA levels in the retina by activation of glial P2X
purinoceptors.
AB - 1. In the rat retina, gamma-aminobutyric acid (GABA) released as a transmitter is
inactivated by uptake mainly into glial cells (Muller cells). Activation of P2
purinoceptors in Muller cells increases [Ca2+]i and the present study was
undertaken to see whether this action affected the glial release of [3H]-GABA
from the superfused rat isolated retina. 2. Adenosine 5'-triphosphate (ATP) and
the P2X-purinoceptor agonists, alpha,beta-methylene-ATP (alpha,beta-meATP) and
beta,gamma-methyleneATP (beta,gamma-meATP) significantly increased the KCl-evoked
release of [3H]-GABA from the retina. 3. Adenosine and the P2Y-purinoceptor
agonist, 2-chloroATP, had no effect on the KCl-evoked release of [3H]-GABA from
the retina. However, 2-methylthioATP (2-Me-S-ATP) significantly enhanced the
evoked release of [3H]-GABA. 4. The effect of ATP on the glial release of [3H]
GABA was abolished by the P2-antagonist, pyridoxalphosphate-6-azophenyl-2',4'
disulphonic acid (PPADS). 5. When the superfused retina was exposed to the GABA
uptake inhibitor, SKF89976A, the enhancing effect of alpha,beta-meATP on the KCl
evoked release of GABA was abolished. 6. The KCl-evoked release of [3H]-GABA from
the frog retina and rat cerebrocortical slices, which take up GABA mainly into
neurones, was not affected by ATP or alpha,beta-meATP. 7. We concluded that the
glial Muller cells in the rat retina possess P2-receptors, activation of which
increases the 'release' of preloaded [3H]-GABA apparently by reducing uptake. On
balance, the results suggest the involvement of P2X-purinoceptors, although we
cannot exclude the possibility that P2Y-purinoceptors may be involved. Our
results suggest that ATP, as well as being a conventional transmitter in the
retina, may be involved in neuronal-glial signalling and modulate the
extracellular concentration of GABA.
PMID- 9641550
TI - Superoxide and endothelium-dependent constriction to flow in porcine small
pulmonary arteries.
AB - 1. The aim of this study was to determine the response of porcine small pulmonary
arteries to intralumenal flow and to identify the cellular mechanisms and
potential mediators involved in the response. 2. Porcine small pulmonary arteries
were isolated from a branch of the main intrapulmonary artery of the lower lung
lobe and studied in a perfusion myograph system that allowed independent control
of transmural pressure and intralumenal flow. At a transmural pressure of 20
mmHg, the baseline internal diameter (BID) of the arteries was 251.2+/-16.1
microm (n=16). 3. Under quiescent conditions or during constriction with U46619
to approximately 60% of BID, intralumenal flow caused reversible constriction in
arteries with endothelium (in the presence of U46619, flow decreased diameter
from 60.0+/-2.5% to 49.5+/-3.0% BID at 10 microl min(-1), n=16, P<0.05) but no
change in diameter of arteries without endothelium. 4. In the presence of
superoxide dismutase (SOD, 150 u ml(-1)), the response to flow was converted from
constriction to vasodilatation (in presence of U46619 and SOD, flow increased
diameter from 54.2+/-3.4% to 76.7+/-4.5% BID at 10 microl min(-1), n=10, P<0.05).
Inhibition of NO synthase with L-NAME (3 x 10(-5) M) abolished the flow-induced
vasodilatation occurring in the presence of SOD and the flow-induced constriction
occurring in the absence of SOD. In arteries with endothelium, L-NAME (3 x 10(-5)
M) caused significant vasoconstriction, whereas SOD did not alter vasomotor tone.
5. Acetylcholine (10(-8) to 10(-6) M) caused endothelium-dependent relaxation of
small pulmonary arteries that was not significantly affected by SOD (150 u ml(
1)) but was inhibited by L-NAME (3 x 10(-5) M). 6. These results suggest that in
small, porcine, isolated pulmonary arteries, intralumenal flow increases the
production of NO but this is obscured by the generation of superoxide which
causes vasoconstriction.
PMID- 9641551
TI - P2X receptors in cochlear Deiters' cells.
AB - 1. The ionotropic purinoceptors in isolated Deiters' cells of guinea-pig cochlea
were characterized by use of the whole-cell variant of the patch-clamp technique.
2. Extracellular application of adenosine 5'-triphosphate (ATP) induced a dose
dependent inward current when the cells were voltage-clamped at -80 mV. The ATP
induced current showed desensitization and had a reversal potential around -4 mV.
3. Increasing intracellular free Ca2+ by decreasing the concentration of EGTA in
the pipette solution reduced the amplitude of the ATP-gated current. 4. The order
of agonist potency was: 2-methylthioATP (2-meSATP)>ATP>benzoylbenzoyl-ATP
(BzATP)>alpha,beta-methyleneATP (alpha,beta,meATP>adenosine 5'-diphosphate
(ADP)>uridine 5'-triphosphate (UTP)>adenosine 5'-monophosphate (AMP)=adenosine
(Ad). 5. Pretreatment with forskolin (10 microM), 8-bromoadenosine-3',5'
cyclophosphate (8-Br-cyclic AMP, 1 mM), 3-isobutyl-1-methylxanthine (IBMX, 1 mM)
or phorbol-12-myristate-13-acetate (PMA, 1 microM) reversibly reduced the ATP
induced peak current. 6. The results are consistent with molecular biological
data which indicate that P2X2 purinoceptors are present in Deiters' cells. In
addition, the reduction of the ATP-gated current by activators of protein kinase
A and protein kinase C indicates that these P2X2 purinoceptors can be
functionally modulated by receptor phosphorylation.
PMID- 9641553
TI - Different effects of gadolinium on I(KR), I(KS) and I(K1) in guinea-pig isolated
ventricular myocytes.
AB - 1. Using the whole cell configuration of the patch clamp technique, we studied
the potential blocking effects of gadolinium (1 microM to 1 mM) on potassium
currents: I(KR), I(KS) and I(K1). The study was performed on guinea-pig isolated
ventricular myocytes. 2. The background current, I(K1) was insensitive to Gd3+.
Thus, we found that no obvious screening of surface charges was visible with
concentrations of Gd3+ up to 100 microM. 3. By use of three different protocols:
tail currents fitting, analysis of envelope of tails and electrophysiological
dissection, we found that I(KR) was the only component of IK that was sensitive
to Gd3+. The sensitivity was apparently different depending on the protocol used.
4. Comparison of the results obtained with the different protocols revealed that
the rapid component of I(KR) is more sensitive to Gd3+ than the slow one. 5. Of
the different protocols used to distinguish between I(KR) and I(KS), the
electrophysiological dissection seems to be the more accurate.
PMID- 9641552
TI - Respiratory and cardiovascular effects of the mu-opioid receptor agonist
[Lys7]dermorphin in awake rats.
AB - 1. Changes in respiratory variables, arterial blood pressure and heart rate were
studied in awake rats after injection of the opioid peptide [Lys7]dermorphin and
its main metabolites, [1-5]dermorphin and [1-4]dermorphin. 2. Fifteen minutes
after injection, doses of [Lys7]dermorphin producing antinociception (i.c.v., 36
120 nmol; s.c., 0.12-4.7 micromol kg(-1)) significantly increased respiratory
frequency and minute volume of rats breathing air or hypoxic inspirates. This
respiratory stimulation was reversed to depression by the 5-HT receptor
antagonist ritanserin (2 mg kg(-1), s.c.), was blocked by naloxone (0.1 mg kg(
1), s.c.), significantly reduced by the mu1 opioid receptor antagonist
naloxonazine (10 mg kg(-1), s.c., 24 h before) but unaffected by peripherally
acting opioid antagonist naloxone methyl bromide (3 mg kg(-1), s.c.). Forty five
minutes after injection, doses of the peptide producing catalepsy (s.c., 8.3-14.2
micromol kg(-1), i.c.v., 360 nmol) significantly reduced respiratory frequency
and volume of rats breathing air and blocked the hypercapnic ventilator response
of rats breathing from 4% to 10% CO2. I.c.v. administration of [1-5]dermorphin
and [1-4]dermorphin (from 36 to 360 nmol) never stimulated respiration but
significantly reduced basal and CO2-stimulated ventilation. Opioid respiratory
depression was only antagonized by naloxone. 3. In awake rats, [Lys7]dermorphin
(0.1-1 mg kg(-1), s.c.) decreased blood pressure. This hypotensive response was
abolished by naloxone, reduced by naloxone methyl bromide and unaffected by
naloxonazine. 4. In conclusion, the present study indicates that analgesic doses
of [Lys7]dermorphin stimulate respiration by activating central mu1 opioid
receptors and this respiratory stimulation involves a forebrain 5
hydroxytryptaminergic excitatory pathway.
PMID- 9641554
TI - Inhibition of nitric oxide generation unmasks vascular dysfunction in insulin
resistant, obese JCR:LA-cp rats.
AB - 1. The effects of nitric oxide (NO) on vascular reactivity and platelet function
in the obese (cp/cp) and lean (+/?) JCR:LA-cp rats were investigated. 2.
Phenylephrine (PE; 0.1 nM-10 microM) induced contraction of isolated aortic rings
in both genotypes (cp/cp and +/?) of JCR:LA-cp rats. The sensitivity to
contraction with PE was enhanced in cp/cp compared with +/? rings. Rings from
both genotypes showed an increased contraction upon removal of the endothelium.
3. Acetylcholine (ACh; 0.1 nM-10 microM)-induced endothelium-dependent relaxation
of rings was not significantly different in the two genotypes. Both were
inhibited to a similar extent by NG-nitro-L-arginine methyl ester (L-NAME; 0.01-1
mM) when administered in vitro. 4. The nitric oxide synthase (NOS) inhibitor (L
NAME; 0.3, 1 or 3 mg ml(-1), p.o.) when administered in vivo increased blood
pressure in cp/cp rats but not in +/? rats. 5. L-NAME resulted in greater
inhibition of ACh-induced relaxation in cp/cp rings compared with +/? rings. 6. L
NAME treatment in vivo caused a decrease in cyclic GMP and NOS activity in rings
from cp/cp but not +/? rats. 7. The NO donor, S-nitroso-N-acetyl-DL-penicillamine
(SNAP; 0.1 nM-10 microM)-induced relaxation of rings from +/? rats, an effect
enhanced by the treatment with L-NAME in vivo. 8. Oral administration of L-NAME
did not enhance the vasorelaxant effect of SNAP on rings of aorta from cp/cp
animals. 9. Platelet aggregation and NOS activity were similar in both genotypes
and were not modified by oral administration of L-NAME. 10. These results show
that unimpaired generation of NO is crucial for maintenance of vascular tone
particularly under conditions of vascular insult exemplified by insulin
resistance, obesity and dyslipidemia detected in cp/cp rats.
PMID- 9641555
TI - Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in
vitro model of epilepsy.
AB - 1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a
change in GABA-metabolism have been suggested as mechanisms of action of
gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA
transaminase but it also interferes with GABA-release and GABA-uptake. On the
basis of these mechanisms of action, a pharmacodynamic interaction of the two
antiepileptic drugs could be supposed which might be of relevance in the sense of
a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments
were carried out on hippocampal slices (n=107) of guinea-pigs (n=70).
Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from
the bath solution and recorded in the stratum pyramidale of the CA3 region.
Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM,
6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100
microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations
up to 600 microM, failed to decrease the repetition rate or duration of e.f.p.
(n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition
rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a
reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h
(n=11). With simultaneous administration of vigabatrin (100 microM) and
gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased
down to 8+/-3%, which is significantly different from the values obtained after
administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic
effect of vigabatrin alone and the enhancement by gabapentin were blocked by the
GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results
demonstrate that gabapentin is able to augment the antiepileptic effects of
vigabatrin significantly. It is possible that a change in the GABA-release
machinery is induced by vigabatrin which then can be augmented by gabapentin.
PMID- 9641556
TI - Characterization of the phencyclidine-induced increase in prefrontal cortical
dopamine metabolism in the rat.
AB - 1. We have investigated the effects of a schizophrenomimetic drug phencyclidine
(PCP) and N-methyl-D-aspartate (NMDA)-related agents alone or in combination on
dopamine metabolism in the medial prefrontal cortex and striatum of the rats by
measuring the tissue concentrations of dopamine and its metabolite, 3,4
dihyroxyphenylacetic acid (DOPAC), and the rate of dopamine disappearance
(dopamine utilization) after its synthesis inhibition. 2. Systemic injection of
PCP and selective, non-competitive, NMDA antagonists caused an increase of both
tissue concentrations of DOPAC and dopamine utilization in the prefrontal cortex
but not in the striatum. The PCP-induced augmentation of cortical dopamine
metabolism was not influenced by selective lesion of ascending noradrenergic
neurones. 3. Intra-prefrontal cortical infusion of PCP or selective competitive
or non-competitive antagonists of the NMDA receptor mimicked the ability of
systemic PCP injection to enhance DOPAC levels and dopamine utilization in the
prefrontal cortex. However, an NMDA antagonist injected into the cell body area
of the mesocortical dopaminergic neurones failed to affect dopamine metabolism in
the prefrontal cortex. 4. The increasing effects of PCP and selective NMDA
antagonists on cortical dopamine utilization were not additive, although a
dopamine receptor antagonist, haloperidol, still accelerated the disappearance of
dopamine, even in the presence of PCP. 5. Intra-cortical or intra-ventricular
infusion of NMDA or D-alanine but not L-alanine, attenuated the ability of
systemic PCP administration to facilitate prefrontal dopamine utilization. 6.
These data suggest that PCP might activate prefrontal cortical dopaminergic
neurones, at least in part, by blocking the NMDA receptor in the prefrontal
cortex which participates in a tonic inhibitory control of the mesoprefrontal
dopaminergic projections.
PMID- 9641557
TI - Investigation of the actions and antagonist activity of some polyamine analogues
in vivo.
AB - 1. The ability of three putative polyamine antagonists to antagonize behavioural
changes induced by spermine was assessed. 2. Injection of an excitotoxic dose of
spermine (100 microg, i.c.v.) in mice results in the development of a
characteristic behavioural profile, which has two temporally distinct phases. The
early events include clonic convulsions, and the later, more general excitation,
includes tremor and culminates in the development of a fatal tonic convulsion. 3.
Co-administration of arcaine (25 microg, i.c.v.) potentiated the early phase
effects after spermine injection, but antagonized the development of spermine
induced tonic convulsions. A larger dose of arcaine (50 microg, i.c.v.) given
alone resulted in the development of spermine-like body tremor and convulsions.
It therefore appears that arcaine is not a pure polyamine antagonist in vivo, but
may be a partial agonist. 4. Similarly, 1,10-diaminodecane appeared to act as a
partial agonist in vivo, although it was less potent than arcaine. 5. In
contrast, diethylenetriamine (DET) effectively inhibited the development of the
early effects of spermine, but was ineffective against the spermine-induced CNS
excitation and tonic convulsions. 6. It is concluded that none of the putative
polyamine antagonists tested behaved as effective polyamine antagonists in vivo,
although each produced some antagonism.
PMID- 9641558
TI - Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain
kynurenic acid.
AB - 1. Nicotinylalanine, an inhibitor of kynurenine metabolism, has been shown to
elevate brain levels of endogenous kynurenic acid, an excitatory amino acid
receptor antagonist. This study examined the potential of nicotinylalanine to
influence excitotoxic damage to striatal NADPH diaphorase (NADPH-d) and gamma
aminobutyric acid (GABA)ergic neurones that are selectively lost in Huntington's
disease. 2. A unilateral injection of the N-methyl-D-aspartate (NMDA) receptor
agonist, quinolinic acid, into the rat striatum produced an 88% depletion of
NADPH-d neurones. Intrastriatal infusion of quinolinic acid also produced a dose
dependent reduction in striatal GABA content. 3. Nicotinylalanine (2.3, 3.2, 4.6,
6.4 nmol 5 microl(-1), i.c.v.) administered with L-kynurenine (450 mg kg(-1)), a
precursor of kynurenic acid, and probenecid (200 mg kg(-1)), an inhibitor of
organic acid transport, 3 h before the injection of quinolinic acid (15 nmol)
produced a dose-related attenuation of the quinolinic acid-induced loss of NADPH
d neurones. Nicotinylalanine (5.6 nmol 5 microl(-1)) in combination with L
kynurenine and probenecid also attenuated quinolinic acid-induced reductions in
striatal GABA content. 4. Nicotinylalanine (4.6 nmol, i.c.v.), L-kynurenine alone
or L-kynurenine administered with probenecid did not attenuate quinolinic acid
induced depletion of striatal NADPH-d neurones. However, combined administration
of kynurenine and probenecid did prevent quinolinic acid-induced reductions in
ipsilateral striatal GABA content. 5. Injection of nicotinylalanine, at doses
(4.6 nmol and 5.6 nmol i.c.v.) which attenuated quinolinic acid-induced striatal
neurotoxicity, when combined with L-kynurenine and probenecid produced increases
in both whole brain and striatal kynurenic acid levels. Administration of L
kynurenine and probenecid without nicotinylalanine also elevated kynurenic acid,
but to a lesser extent. 6. The results of this study demonstrate that
nicotinylalanine has the potential to attenuate quinolinic acid-induced striatal
neurotoxicity. It is suggested that nicotinylalanine exerts its effect by
increasing levels of endogenous kynurenic acid in the brain. The results of this
study suggest that agents which influence levels of endogenous excitatory amino
acid antagonists such as kynurenic acid may be useful in preventing excitotoxic
damage to neurones in the CNS.
PMID- 9641559
TI - Inhibition of NMDA-gated ion channels by the P2 purinoceptor antagonists suramin
and reactive blue 2 in mouse hippocampal neurones.
AB - 1. The action of suramin and reactive blue 2 on N-methyl-D-aspartate (NMDA)
activated ion current was studied in mouse hippocampal neurones in culture by use
of whole-cell patch-clamp recording. 2. Suramin and reactive blue 2 inhibited
steady-state current activated by 25 microM NMDA with IC50 values of 68 and 11
microM, respectively. 3. Reactive blue 2 produced a gradual decline of NMDA
activated current to a steady-state, but this slow onset was not an indication of
use-dependence, as it could be eliminated by exposure to reactive blue 2 before
NMDA application. In addition, NMDA-activated current recovered completely from
inhibition by reactive blue 2 in the absence of agonist. 4. The slow onset of
inhibition by reactive blue 2 was not apparently due to an action at an
intracellular site, as inclusion of 250 microM reactive blue 2 in the recording
pipette did not alter inhibition by 25 microM reactive blue 2 applied externally.
5. Reactive blue 2 and suramin inhibited NMDA-gated channels in a voltage
independent manner. 6. Reactive blue 2, 25 microM, decreased the maximal response
to NMDA from 1441 to 598 pA without changing its EC50. In contrast, 75 microM
suramin increased the EC50 for NMDA from 13 to 35 microM, and decreased the
maximal response to NMDA from 1822 to 1498 pA. Schild analysis of suramin
inhibition of NMDA-activated current yielded a nonlinear plot. 7. Both agents
decreased the maximal response to glycine without altering its EC50. 8. Suramin
and reactive blue 2 appear to inhibit NMDA receptor-channels in a manner that is
noncompetitive with respect to both NMDA and glycine. However, inhibition by
suramin differed from that by reactive blue 2, in that suramin significantly
increased the EC50 of NMDA.
PMID- 9641560
TI - The profile of sabcomeline (SB-202026), a functionally selective M1 receptor
partial agonist, in the marmoset.
AB - 1. Sabcomeline (SB-202026, 0.03 mg kg(-1), p.o.), a potent and functionally
selective M1 receptor partial agonist, caused a statistically significant
improvement in the performance of a visual object discrimination task by
marmosets. No such improvement was seen after RS86 (0.1 mg kg(-1), p.o.). 2.
Initial learning, which only required an association of object with reward and an
appropriate response to be made, was not significantly affected. Reversal
learning, which required both the extinction of the previously learned response
and the acquisition of a new response strategy, was significantly improved after
administration of sabcomeline (0.03 mg kg(-1), p.o.). 3. Sabcomeline (0.03 and
0.1 mg kg(-1), p.o.) had no significant effect on mean blood pressure measured
for 2 h after administration in the conscious marmoset. 4. Sabcomeline (0.03 mg
kg(-1), p.o.) caused none of the overt effects such as emesis or behaviours often
seen after the administration of muscarinic agonists, e.g. face rubbing and
licking. 5. This is the first study to demonstrate cognitive enhancement by a
functionally selective M1 receptor partial agonist in a normal (i.e. non
cognitively impaired) non-human primate and this effect was seen at a dose which
did not cause side effects. 6. Perseverative behaviour and deficient acquisition
of new information are seen in patients with Alzheimer's disease (AD). Therefore
the data suggest that sabcomeline might be of therapeutic benefit in the
treatment of AD.
PMID- 9641561
TI - Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in
which both mdr1a and mdr1b genes have been disrupted.
AB - 1. We have used mice with homozygously disrupted mdr1a and mdr1b genes (mdr1a/1b
(-/-) mice) to study the role of the mdr1-type P-glycoprotein (P-gp) in the
elimination of cationic amphiphilic compounds from the body. These mice lack drug
transporting P-gps, but show no physiological abnormalities under laboratory
conditions and have normal bile flow. 2. 3H-labelled cationic drugs were
administered intravenously (i.v.) to mice as a single bolus dose and the
disposition of the studied cationic drugs was investigated by focusing on drug
secretion into bile, intestinal lumen and urine. 3. Hepatobiliary secretion of
the investigated cationic drugs was profoundly reduced in mice devoid of the mdr1
type P-gps. In fact, the cumulative biliary output, measured during 1 h, of the
small type 1 compounds tri-butylmethyl ammonium (TBuMA) and azidoprocainamide
methoiodide (APM), as well as of the more bulky type 2 cationic drug vecuronium,
was reduced by at least 70% in the mdrla/lb (-/-) mice compared to wild-type. 4.
The intestinal secretion of TBuMA, APM and vecuronium was also profoundly reduced
in mdrla/lb (-/-) mice compared to wild-type mice. The absence of the mdrl-type P
gp resulted in virtual elimination of intestinal secretion of TBuMA and APM (>90%
reduced as compared to wild-type (P=0.0001 and 0.0022, respectively)). The
intestinal secretion of the type 2 cation drug vecuronium was reduced by 58%
(P=0.0004) compared to the wild-type mice. 5. Increased renal clearances of both
the type 1 compounds TBuMA and APM and also of the type 2 cationic compound
vecuronium in the mdrla/lb (-/-) mice were observed. Furthermore, the balance
between hepatic, intestinal and renal clearances of small type 1 organic cations
clearly shifted towards a predominant role for renal clearance. Increased renal
clearance may be explained by (over)expression of additional mechanisms for renal
organic cation secretion, alternatively they may also point to an as yet
undefined role of P-glycoprotein in kidney physiology and renal secretory
function. 6. We conclude that the elimination from the body of a broad spectrum
of cationic amphiphilic drugs via liver and intestine, is largely dictated by the
activity of mdrl-type P-glycoproteins.
PMID- 9641562
TI - Genes for asthma on chromosome 11: an update.
PMID- 9641563
TI - Nasal immunotherapy--not to be sneezed at.
PMID- 9641564
TI - Pollinosis in the southern Europe--Mediterranean area.
PMID- 9641565
TI - Exclusion of chromosome 11q and the FcepsilonRI-beta gene as aetiological factors
in allergy and asthma in a population of Dutch asthmatic families.
AB - BACKGROUND: The beta subunit of the high-affinity receptor for IgE (FcepsilonRI
beta) is localized to chromosome 11q13 and has been reported by Cookson et al. to
be in close genetic linkage with a gene for atopy. A maternally inherited
association was found between the presence of a variant of FcepsilonRI-beta,
Ile181Leu, and high total serum IgE levels (IgE > 100 IU). In a previous study of
20 Dutch families, we found no evidence for linkage of atopy or bronchial
hyperresponsiveness (BHR) to chromosome 11q. OBJECTIVE: Recently segregation
analysis in 92 families has given us evidence for two independent major loci
accounting for 78% of the observed variance in total serum IgE levels, and
linkage analysis using both sib-pair and LOD score methods has identified one
major locus for regulation of IgE levels and BHR near the cytokine gene complex
on chromosome 5q. The objective of this study is to pursue the identification of
the second major locus. METHODS: We have studied markers in the area of the high
affinity IgE receptor (FcepsilonRI-beta) on chromosome 11q (D11S1314, FcepsilonRI
beta and D11S987) in 83 families for whom DNA was available. Furthermore, our
families have been examined for variance in the FcepsilonRI-beta gene,
specifically for Leu181 and Leu181/Leu183 mutations. RESULTS: By sib-pair
analysis, there is no evidence for linkage of total serum IgE levels or number of
positive skin tests to these markers in our population. Similar negative results
were obtained for affected sib-pair analysis of BHR, with the exception of
D11S1314, which was significant at P=0.046. The FcepsilonRI-beta gene in 36
female probands, 44 male probands and 46 female spouses was sequenced for these
mutations. For each of these 126 individuals sequencing of FcepsilonRI-beta
demonstrated a wild-type sequence pattern, with no mutations found in anyone,
male or female. CONCLUSION: We are unable to confirm the presence of significant
mutations in FcepsilonRI-beta gene in our population, and we cannot confirm that
the FcepsilonRI-beta gene is crucial to the pathogenesis of allergic inflammation
in asthma.
PMID- 9641566
TI - Decrease of allergen-specific T-cell response induced by local nasal
immunotherapy.
AB - BACKGROUND: The clinical efficacy and safety of local nasal immunotherapy (LNIT)
with lyophilized 'macronized' powder has been demonstrated. However, the
immunological changes possibly induced by LNIT which may account for the clinical
improvement are still unclear. OBJECTIVE: To investigate the effects of a
successful LNIT-treatment on the allergen-driven T cell response, cytokine
secretion and IgE and IgG antibody production. METHODS: Three groups (untreated,
subcutaneous immunotherapy- SIT- and LNIT-treated) of grass-sensitive patients
suffering from seasonal rhinitic symptoms were ramdomized for the 2-year study.
The proliferative response of PBMC to purified Rye-1 allergen and serum levels of
grass-specific IgE and IgG were evaluated before treatment and during the 2-year
subsequent pollination periods. The proliferative response of allergen-specific
short-term T-cell lines, as well as production of allergen-driven cytokine by
PBMC, were also assessed. RESULTS: Both SIT and LNIT induced a significant
reduction of symptom scores during the pollination season. SIT, but not LNIT,
induced a significant change in serum levels of allergen-specific IgE and IgG
antibody. By contrast, both SIT and LNIT reduced the increase of the
proliferative response of allergen-specific T cells driven by natural allergen
exposure and significantly decreased T cell proliferation to low doses of
allergen, as shown also by the mitogenic index of allergen-specific T-cell lines.
A reduced IL-4 and IFNgamma production by PBMC of LNIT- and SIT-treated patients
was also observed in the absence of a clearcut TH2-TH1 switch. CONCLUSIONS: These
data suggest that a common mechanism of both LNIT and SIT is the induction of T
cell tolerance, thus providing a rational basis to explain why LNIT may be
clinically successful in allergic patients with rhinits.
PMID- 9641567
TI - Olive pollen allergy: searching for immunodominant T-cell epitopes on the Ole e 1
molecule.
AB - BACKGROUND: The amino-acid and nucleotide sequence of Ole e 1 (the major antigen
of olive pollen) has been described and the IgE antibody response to this major
allergen was associated with DR7/DQ2 antigens. With this previous data we try to
define the T-cell epitopes implicated in Ole e 1 reactivity. OBJECTIVES: To study
the recognition of T cells (derived from allergic and non-allergic Ole e 1
patients) to Ole e 1 synthetic peptides in order to define immunodominant T-cell
epitopes. METHODS: We have compared the proliferative response of the peripheral
blood mononuclear cells from Ole e 1 sensitized patients vs. non-sensitized
controls, induced by 14 Ole e 1 synthetic peptides. Thirty subjects were
classified in two groups: group 1 (non-responders against Ole e 1, n=16) and
group 2 (Ole e 1 responders, n=14), according to their clinical parameters and
the presence or not in their sera of the significant Ole e 1 IgE antibody levels.
RESULTS: Our results shown that it is possible to find T cells reactive to Ole e
1 peptides in patients with and without significant levels of Ole e 1 IgE
antibodies. However, the percentage of response was higher in patients with IgE
antibodies 71.4% vs 25%), and the recognition profile was different: the control
group showed a broad reactivity pattern, in contrast, the response by the 'Ole e
1 responders' group was mainly directed against three peptides of the carboxi
terminal region, peptides 10 (91-102), 12 (109-120) and 13 (119-130), with a
response frequency of 35.7, 28.5 and 28.5%, respectively. By direct and
inhibition test no antibody response was found against the synthetic peptides.
CONCLUSIONS: Our data suggest that the regions between 91 and 102 and 109-130
aminoacids on the Ole e 1 molecule are immunodominant T-cell epitopes. These
epitopes are not recognized by IgE antibodies.
PMID- 9641568
TI - Preserved epitope-specific T cell activation by recombinant Bet v 1-MBP fusion
proteins.
AB - BACKGROUND: Allergen-specific T cells play an important role in the allergic
immune response, and are thought to be the principal target in specific
immunotherapy. OBJECTIVE: The aim of the present study was to evaluate if fusion
proteins of allergens with bacterial proteins can be used to activate and bias
allergen-specific T cells, and to characterize T cell epitopes. METHODS: The
complete gene of Bet v 1, the major birch pollen allergen, was amplified by PCR
from birch pollen mRNA, and cloned in pKK223-3. The complete gene or truncated
sequences were transferred to pMAL-c and expressed in E. coli as fusion proteins
with maltose binding protein (MBP). The complete fusion protein, and the
truncated fusion proteins were used for studies with Bet v 1-specific T cells.
RESULTS: Bet v 1-specific T cells reacted similarly with purified and crude Bet v
1-MBP proteins. Therefore, crude preparations were used to study the epitope
specificity of 11 Bet v 1-specific T cell clones. Six distinct T cell epitopes
were determined in this way. Interestingly, the T cell epitope of three T cell
clones, that did not react with synthetic peptides in a previous study, was
identified. In addition, the presence of MBP as a fusion partner to Bet v 1 was
shown to influence TH2/TH1 cytokine production in T cell lines, but not in
established T cell clones. CONCLUSION: Using crude preparations of recombinant
fusion proteins of Bet v 1 with MBP, multiple T cell epitopes were identified in
Bet v 1. As T cell activation is preserved in this system, the generation of
recombinant allergens with TH1-inducing proteins as fusion partners might be
considered as a T-cell targeted approach for specific immunotherapy.
PMID- 9641569
TI - Identification of HLA-DR and -DQ alleles conferring susceptibility to pollen
allergy and pollen associated food allergy.
AB - BACKGROUND: Allergenic crossreactivity of pollen and foods due to the antigeneic
similarity of oligopeptides is a well established clinical phenomenon. OBJECTIVE:
To determine the immunopathological relevance of antigen presentation, we
analysed the HLA class-II genotype of patients with either pollen allergy or
pollen associated food allergy. METHODS: One hundred and twenty patients with
pollen allergy and 80 patients with pollen associated food allergy were evaluated
by skin- prick tests, RAST, and HLA class-II genotyping. The control population
comprised 4251 healthy blood and bone marrow donors. RESULTS: Monovalent pollen
allergy was observed in 57% (n=68) of patients with pollinosis (57x grass pollen,
11x birch pollen), but only in 15% (n=12) of patients with food allergy (9x grass
pollen, 3x birch pollen). Hazelnut (71%), almond (65%), walnut (44%) and apple
(41%) were the most common food allergens and frequently associated with birch
pollen allergy. Grass pollen allergy was associated with an increased frequency
of HLA-DQB1*0301 (RR=2.3; EF=0.4; P=0.0016) when compared with the control
population. HLA-DRB *08 conferred a sixfold higher risk for peanut allergy
(EF=0.3; P=0.0013) and -DRB1*12 a 13-fold higher risk for carrot allergy (EF=0.3;
P<0.000001). The differences on allele frequencies detected among patients with
food allergies diminished or turned statistically insignificant when their
genotypes were directly compared to those of patients with the corresponding
pollen allergies. This was found in the case of birch pollen associated hazel nut
allergy for the extended haplotype HLA-DRB1*01, -DQA1*0101, -DQB1*0501 as well as
in grass pollen associated peanut allergy for HLA-DRB1*08 (from RR=6, P=0.0013 to
insignificant) and in birch pollen associated carrot allergy for HLA-DRB1*12
(from RR=13, P < 0.000001 to insignificant). CONCLUSION: We were able to identify
HLA class-II alleles associated with some allergies thus indicating that these
alleles might confer susceptibility to the respective allergens. Similarities at
the level of the HLA class-II genotype parallel the empirical finding of distinct
cross-reactivity patterns thus complementing investigations of IgE specificities.
Our observations provide evidence for the major importance of antigen
presentation on the manifestation of distinct crossreactivity patterns.
PMID- 9641570
TI - Beta2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not
associated with asthma in an adult population.
AB - OBJECTIVE: To determine the association between the beta2-adrenoceptor
polymorphisms at amino acids 16 and 27 and markers of allergic disease and asthma
per se in a random adult population, and to determine the degree of linkage
disequilibrium existing between polymorphisms at amino acid positions 16, 27, 164
and nucleic acid residue 523. METHODS: We measured serum IgE, skin-prick test
positivity, atopy, bronchial hyperreactivity, wheeze and asthma (self-reported
and doctor-diagnosed), and determined beta2-adrenoceptor genotype by allele
specific oligonucleotide hybridization, in 630 adults aged between 18 and 70,
selected from the electoral role in a local health authority in Nottingham.
RESULTS: Homozygotes for the Glycine 16 polymorphism had a significantly higher
incidence of atopy (chi2=6.44 (Pearson's), P=0.04). We also observed a
significant association between the Glycine 16 allele and atopy (chi2=4.13
(Pearson's), P=0.04), when we assumed the Glycine 16 allele to operate in a
dominant mode. No other significant associations between beta2-adrenoceptor
polymorphisms and markers of allergic disease and asthma per se were observed.
Marked linkage disequilibrium exists between the beta2-adrenoceptor polymorphisms
at amino acid 16 and 27 (D=0.38, chi2 P<0.0001), and between the beta2
adrenoceptor polymorphisms at amino acid 27 and nucleic acid residue 523 (C-A)
(D=0.36, chi2 P<0.0001). CONCLUSION: There is no consistent association between
beta2-adrenoceptor polymorphisms and the risk of developing allergic disease or
asthma per se in this adult sample. Marked linkage disequilibrium exists between
the amino acid 16 and 27 polymorphisms, and also between the amino acid 27
polymorphism and the nucleic acid residue 523 (C-A) polymorphism. This
polymorphism accounts for the Ban 1 RFLP previously described at the beta2
adrenoceptor locus on chromosome 5q 31.
PMID- 9641571
TI - Association of asthma and the interleukin-4 promoter gene in Japanese.
AB - BACKGROUND: Susceptibility to the development of asthma and other atopic diseases
is known to be associated with genetic components. Several investigator have
linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5
to atopy and asthma. Recent study has demonstrated that the T allele of a
polymorphism in the IL-4 gene promoter region (C-590T) is associated with
elevated levels of total serum IgE. OBJECTIVE: The objective of this study was to
evaluate the possible role of this IL-4 polymorphism (C-590T) in modulating the
allergic response and asthma in Japanese children. METHODS AND RESULTS: The study
was conducted in two different populations: families ascertained through
asthmatic children (asthmatic group, 306 members) in whom linkage of asthma and
atopy to chromosome 5q31-33 is suggested and a random general population (control
group, 215 members). The IL-4 C-590T polymorphism was genotyped by PCR
restriction fragment length polymorphism analysis. Frequency of the T allele was
0.73 in the asthmatic group and 0.70 in the control group. No significant
difference in the levels of total serum IgE and specific IgE to house dust mite
was observed between subjects with homozygote for the C allele, a heterozygote
and a homozygote for the T allele by intrafamilial and interfamilial comparisons.
Using the transmission disequilibrium test, however, we found a significantly
frequent transmission of the T allele to asthmatic children (chi2=5.72, P=0.023).
CONCLUSION: Our data suggest that the IL-4 promoter C-590T polymorphism may be
associated with the development of asthma in Japanese children, but not through
modulating total serum IgE levels.
PMID- 9641572
TI - Validation of a screening questionnaire for atopy with serum IgE tests in a
population of pregnant Dutch women.
AB - BACKGROUND: We have started a large birth cohort study in which pregnant women
with and without atopy are differentially included. In view of the large number
of subjects to be screened (12000), a simple questionnaire was developed for the
assessment of atopy in pregnant women. OBJECTIVE: The objective of our study was
to evaluate the efficacy of a questionnaire using serum IgE tests. METHODS:
During a antenatal visit to the midwife clinic, 175 expecting mothers completed a
questionnaire and from each subject blood was obtained in which total and
specific IgE against house dust mite, cat, dog, birch and grass was determined.
RESULTS: When atopy was defined as the presence of a positive test for IgE
against at least one allergen, seven questions from the questionnaire had a
sensitivity and specificity of 55.0% and 88.7%, respectively. With the use of the
questionnaire it was possible to select about 50% of the subjects with specific
IgE to one or more common inhalant allergens. The positive predictive value of
the screening questions was 71.7%. Taking total IgE into account did not change
these results. CONCLUSION: The screening questionnaire is an efficient tool for
differential inclusion of subjects with and without atopy in epidemiological
studies.
PMID- 9641573
TI - Indoor airborne fungal spores, house dampness and associations with environmental
factors and respiratory health in children.
AB - BACKGROUND: Children living in a damp house are more likely to suffer from
respiratory symptoms and it has been suggested that exposure to fungi is an
important contributing factor. However, more knowledge about underlying
mechanisms for the association are needed. OBJECTIVE: To identify associations
between measures of house dampness, levels of airborne fungal spores, housing
factors and health outcomes in children. METHODS: Eighty households with 148
children between 7 and 14 years of age were recruited in the Latrobe Valley,
Victoria, Australia. Some 36% of participating children were asthmatic. Six
sampling visits were made to each house between March 1994 and February 1995 on a
2-monthly cycle. Samples for airborne total and viable fungal spores were
collected from bedrooms, living rooms, kitchens and outdoors. A detailed dwelling
characterization, using a questionnaire and inspection surveys, was carried out.
Skin-prick tests were performed with extracts of common aeroallergens and a
respiratory questionnaire was completed for each child. RESULTS: Large airborne
fungal spore concentrations were recorded in association with: musty odour, water
intrusion, high indoor humidity, limited ventilation through open windows, few
extractor fans and failure to remove indoor mould growth. Visible mould growth or
condensation evidence was associated with large concentrations of Cladosporium
spores, but not with large total spore concentrations. Penicillium exposure was a
risk factor for asthma, while Aspergillus exposure was a risk factor for atopy.
Fungal allergies were more common among children exposed to Cladosporium or
Penicillium in winter or to musty odour. Respiratory symptoms were marginally
more common with exposure to Cladosporium or total spores in winter. CONCLUSION:
Indoor exposure to certain fungal genera in winter was a risk factor for asthma,
atopy and respiratory symptoms in children. On the other hand, no significant
associations were seen between average viable or total spore concentrations and
child health. Actual measurements of fungal spores predict health outcomes better
than reported dampness.
PMID- 9641574
TI - Acoustic rhinometry, rhinomanometry and the amount of nasal secretion in the
clinical monitoring of the nasal provocation test.
AB - BACKGROUND: The reliable interpretation of the nasal provocation test in allergy
diagnosis requires objective and measurable monitoring parameters for clinical
practice. The clinical usefulness of the nasal provocation test has been limited
by scanty knowledge of the specificity and sensitivity of the test and a lack of
reference values. OBJECTIVE: To test and compare three objective monitoring
parameters of a nasal provocation test in occupational allergic rhinitis. To
evaluate the magnitude of the nasonasal effects in a unilateral allergen
challenge. METHODS: The monitoring parameters of the nasal reaction were derived
from the minimum cross-sectional area on acoustic rhinometry, the nasal
resistance on active anterior rhinomanometry and the amount of nasal secretion
measured at 15 min intervals for 60 min. Twenty-three bovine-allergic dairy and
beef cattle farmers and 19 exposed, non-allergic control subjects were challenged
first with a control solution and then with the cow allergen. RESULTS: All the
three monitoring parameters showed high specificity and sensitivity in finding
allergic and non-allergic subjects. The secretion parameter was found to be
slightly superior to the acoustic rhinometry and rhinomanometry parameters. The
side difference in the nasal response between the allergen-challenged and the
contralateral diluent-challenged cavity was significant for all the parameters
among the allergic subjects. The contralateral secretion amount was 1/3 of the
ipsilateral secretion, indicating the magnitude of the contralateral nasonasal
reflex. A nasonasal reflex was also noted in the nasal patency monitoring. The
coefficient of variation was significantly lower for the acoustic rhinometry than
for the rhinomanometry (P=0.0001). The optimal threshold values for a positive
test were a secretion amount of 100 mg, a 15% decrease in the minimum cross
sectional area and a 50% increase in the resistance for the observation period of
30 min and correspondingly 210 mg, 30% and 100% for 60 min. CONCLUSION: The low
pressure aspiration of the nasal secretion from the anterior part of the nasal
cavity was found to be a reliable and practical monitoring parameter to be used
together with acoustic rhinometry or rhinomanometry in the nasal provocation test
for clinical purposes. Although significant nasonasal effects took place in the
unilateral allergen challenge, the response was more prominent in the allergen
challenged than in the contralateral diluent-challenged nasal cavity in most
allergic subjects.
PMID- 9641575
TI - Inhalant allergy to egg yolk and egg white proteins.
AB - BACKGROUND: Several egg white and egg yolk and avian proteins have been described
as a cause of inhalant allergy. Sometimes inhalational type I hypersensitivity to
these proteins is associated with food allergy to egg. OBJECTIVE: We studied two
patients who experienced respiratory and food allergic symptoms upon exposure to
egg or avian antigens through the inhalative or digestive routes. Clinical and
immunological studies were carried out in order to identify individual allergens
from these sources that could be responsible for crossreactivity reactions.
RESULTS: Patient 1 showed IgE sensitization to egg yolk livetins, feathers, and
chicken serum. Specific bronchial challenge with chicken albumin and livetin
extracts elicited a positive early asthmatic response and an increase in serum
eosinophil cationic protein. Immunoblot and CAP-inhibition studies in this
patient supported that chicken albumin (alpha-livetin) was the crossreactive
antigen present in egg yolk and chicken serum and feathers. Patient 2 showed
sensitization to egg white, ovomucoid and lysozyme. However, SDS-PAGE and
immunoblot studies demonstrated contaminating lysozyme in the ovomucoid extract
and identified lysozyme as the main allergen causing egg sensitization in this
patient. Conjunctival challenge test confirmed allergy to lysozyme. CONCLUSION:
Egg yolk and egg white proteins may act not only as ingested allergens but also
as aeroallergens. Immunological studies using highly purified preparations of egg
proteins are useful for the accurate diagnosis of allergic reactions to egg
proteins and to identify individual allergens that may be responsible for
crossreactivity reactions.
PMID- 9641576
TI - Stability of Pityrosporum ovale allergens during storage.
AB - BACKGROUND: Pityrosporum ovale is a common saprophyte on the skin capable to
induce IgE antibody production in atopic dermatitis. Generally IgE response to P.
ovale has been established with skin-prick test, but the stability of P. ovale
skin test allergens is not known. OBJECTIVE AND METHODS: In this study we
analysed the stability of identified allergens of P. ovale in skin test solutions
during storage. The stability was checked with immunoblotting and densitometry
after different time periods and at various temperatures. RESULTS: Coomassie
Brilliant blue staining clearly showed, that proteins were preserved poorly at +
20 degrees C in 50% glycerol. Even extracts stored at + 4 degrees C during 6 and
12 months in 50% glycerol were degraded. Only extract stored at + 4 degrees C for
1 month in 50% glycerol was quite well preserved. According to densitometry
results the 9 kDa band was the most stable main protein allergen. The 20 kDa and
especially the 96 kDa bands were far more labile. The stability of low molecular
allergens was in general better than the stability of high molecular weight
allergens. CONCLUSIONS: The stability of P. ovale extracts stored for more than 1
month was poor even when kept at + 4 degrees C temperature. Reliability of
negative skin prick results should be questioned when older extracts are used. In
skin test negative cases, the sensitization should be evaluated also with the
measurement of specific serum IgE antibodies to P. ovale.
PMID- 9641577
TI - Increased interleukin-6 production during the acute phase of the syndrome of
episodic angioedema and hypereosinophilia.
AB - BACKGROUND: The Gleich syndrome is rare and associates recurrent angioedema,
urticaria, fever, weight gain and blood hypereosinophilia, underlying systemic
and local inflammation. The pathogenesis of those symptoms remains unclear.
OBJECTIVE: We wanted to address the possible implication of Interleukin-6 (IL-6)
in the development of those clinical features, and to identify the cells involved
in its production. METHODS: A 26-year-old man suffering of this disease was
referred in hospital. During an acute attack with weight gain, fever and a
diffuse oedema, a marked increase in eosinophils count (42700/mm3 was observed.
Serum ECP was elevated at 47 microg/L (normal less than 16). Corticosteroid
therapy administrated on the 7th day was followed by a rapid remission. Blood
samples were collected (before, during the attack and under corticosteroid
therapy) for measurements of serum IL-6 (ELISA, Immunotech, Marseille, France)
and plasma histamine (RIA, Immunotech, Marseille, France). Blood monocytes and
eosinophils were isolated and a skin biopsy was performed during the attack.
RESULTS: The plasma histamine level was within normal range. The level of IL-6 in
sera peaked to 74 pg/mL, concomitant with the peak of eosinophilia at the acute
phase phase of the attack. Under corticosteroids, we observed a drop in the IL-6
serum level to 29 pg/mL, concomitant with the clinical remission. During the
attack, an increase in IL-6 production was observed in 24 h blood monocyte
supernatants (11.10(3) pg/mL compared with 2.4+/-0.8.10(3) pg/mL for BM from
controls) as well as in skin endothelial cells but not in the blood and skin
eosinophils. In vitro, when endothelial cells were incubated in eosinophils
supernatants of the patient, liberation of IL-6 was observed (3.3 10(3) pg/mL
compared with controls: 2.1 10(3) pg/mL) CONCLUSION: Serum IL-6 elevation may be
related to an increased production by blood monocytes and endothelial cells,
possibly stimulated by eosinophil mediator during the acute phase of the disease,
and might participate in the inflammatory reaction of this syndrome.
PMID- 9641579
TI - Mechanisms of acute eosinophilic inflammation in a case of acute eosinophilic
pneumonia in a 14-year-old girl.
AB - BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by respiratory
distress, eosinophilic infiltration in the lung, acute onset, resolution of
symptoms with corticosteroids and the absence of relapse. Studies to identify the
pathophysiology of AEP in adults have demonstrated eosinophil activation in the
BAL fluid, and the presence of high levels of interleukin 5 (IL-5) in the BAL.
OBJECTIVE: To investigate the pathophysiology of AEP with pleural effusion in a
paediatric patient. METHODS: ECP levels in the BALand pleural fluid was
determined by radioimmunoassay. IL-5 and GM-CSF concentrations in the BAL and
pleural fluid were measured by Elisa. Immunohistochemistry studies performed on
open lung biopsy included a specific ICAM-1 immunostaining and a ECP specific
immunostaining (EG2+). RESULTS: High levels of ECP were found in the BAL (5
microg/L) and pleural fluid (750 microg/L) demonstrating eosinophil activation at
these sites. Immunohistochemistry illustrated activated (EG2+) eosinophils in the
interalveolar septa and alveolar space and detected increased expression of ICAM
1 on alveolar epithelial cells. High levels of IL-5 were measured in the BAL
(1334 pg/mL) and pleural fluid (7014 pg/mL), while elevated concentrations of GM
CSF (150 pg/mL) were found in the BAL. CONCLUSION: We conclude that in this
paediatric patient with AEP activated eosinophils were present in the BAL fluid,
in the interalveolar septa and in the pleural space while increased ICAM-1
expression was detected on alveolar epithelial cells, contributing, at least
partly, for their adhesive interactions. IL-5 and GM-CSF are likely important to
the massive eosinophil recruitment and activation in the lung, while IL-5 is
probably related to eosinophil accumulation and activation in the pleural space.
Thus, lung generation of eosinophil-active cytokines is central to the
pathophysiology of AEP in paediatric patients.
PMID- 9641578
TI - Mite antigen-induced IL-4 and IL-13 production by basophils derived from atopic
asthma patients.
AB - BACKGROUND: There is increasing evidence for the role of basophils in the
pathogenesis of atopic diseases such as bronchial asthma, atopic dermatitis and
atopic rhinitis. Recently, it has been reported that basophils derived from
healthy donors produce the immunoregulatory cytokines interleukin (IL)-4 and IL
13 after cross-linking of cell surface IgE. In addition to well-known
inflammatory mediators, such as histamine and leukotriene C4. these cytokines
produced by basophils are also considered to be associated with atopic diseases.
OBJECTIVE: Our first objective was to determine whether or not mite-sensitive
atopic asthmatic basophils produce IL-4 and IL-13 in response to mite antigens.
Our second objective was to investigate the relationship between antigen-specific
or nonspecific IgE in the serum and the production of these cytokines in order to
determine the association of basophil-derived cytokines with the pathogenesis of
atopic asthma. Our final objective was to study how production of these cytokines
could be regulated by some anti-asthma drugs. METHODS: Basophils were purified
from peripheral venous blood of 67 atopic asthma patients with elevated RAST for
the house dust mite. Cells were stimulated with mite antigens for 6 hours and
then IL-4 and IL-13 levels in the supernatants were measured by enzyme-linked
immunosorbent assay (ELISA). RESULTS: Mite-sensitive asthmatic basophils produced
IL-4 and IL-13 when stimulated with mite antigens. Mite-induced IL-4 production
peaked at 6 hours after the stimulation. whereas IL-13 production continued up to
24 hours. The higher the concentration of mite-specific IgE but not total IgE
released in the serum, the more IL-4 and IL-13 were produced by basophils in
response to mite antigens. The production of these cytokines was significantly
suppressed by the anti-asthma drugs theophylline (IL-4, p<0.001, n=6; IL-13,
p<0.001, n=10) and dexamethasone (IL-4, p<0.001, n=15; IL-13, p<0.001, n=10).
CONCLUSION: Mite-antigen-induced IL-4 and IL-13 production by basophils derived
from mite-sensitive asthma patients was associated with the concentration of mite
specific IgE and may play an important role in the pathogenesis of atopic asthma.
The inhibitory effect of dexamethasone and theophylline on allergic inflammation
may be due to the inhibition of IL-4 and IL-13 production not only by T cells but
also by basophils.
PMID- 9641580
TI - Anaphylactic reactions associated with trimethoprim.
AB - BACKGROUND: Anaphylactic reactions to cotrimoxazole are often ascribed to the
sulphamethoxazole component of this antibacterial drug. OBJECTIVE: To determine
whether the trimethoprim component can be the cause of an anaphylactic reaction.
METHODS: An analysis was made of reports on anaphylaxis attributed to
trimethoprim, as notified to the Drug Safety Unit of the Dutch Inspectorate for
Health Care. RESULTS: In the period between September 1981 and November 1995, 13
such reports were received. Nine were classified as probable anaphylaxis. Of
these, the causal relationship between exposure to trimethoprim and anaphylaxis
was classified as definite in three reports, and as probable in the other six.
The remaining four reports were classified as possible anaphylaxis. In one of
these, the causal relationship was classified as definite, and in three as
probable. CONCLUSION: Although anaphylaxis due to trimethoprim seems to be rare,
it may be more common than previously thought. Apparently, anaphylaxis to
cotrimoxazole is not always caused by sulphamethoxazole.
PMID- 9641582
TI - Symptoms and objective measures to define the asthma phenotype.
PMID- 9641581
TI - PDE4 inhibition and a corticosteroid in chronically antigen exposed conscious
guinea-pigs.
AB - BACKGROUND: The physiological and pharmacological consequences of repeated aero
allergen challenge have not been previously characterized in conscious,
sensitized guinea-pigs. OBJECTIVES: This study was undertaken to compare the
effects of two anti-inflammatory compounds, dexamethasone and Ro 20- 1724, on an
acute and chronic airway inflammation, in terms of airway function, reactivity
and leucocyte infiltration. METHODS: Sensitized guinea-pigs received eight saline
or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type
4 PDE inhibitor, Ro 20-1724 (3 mgkg(-1)), or dexamethasone (1.5 mg/kg(-1)), 30
min before and 6 h after each challenge. Airway function of the conscious animal
(sGaw) was monitored over the duration of the first and final OvA challenge.
Airway reactivity to the thromboxane mimetic, U46619, was also determined
following the final OvA exposure as was the leucocyte infiltration. RESULTS: The
first antigen challenge induced a large early (0-3h) and smaller late (17-24h)
bronchoconstrictor response. Neither phase was affected by the drug treatments.
The final OvA challenge induced early and late phase bronchoconstrictor responses
but of similar magnitude. The late phase was also significantly prolonged. Ro 20
1724 and dexamethasone significantly attenuated both phases. Airway reactivity to
the inhaled thromboxane mimetic, U46619, was also significantly enhanced at 120h
after the final OvA exposure in contrast to the saline challenged group. This
hyperreactivity was attenuated by Ro 20-1724 and dexamethasone. Bronchoalveolar
lavage after repeated OvA exposures revealed eosinophilia which was attenuated by
Ro 20-1724 and dexamethasone. CONCLUSIONS: This model demonstrates differential
airway responses to acute and chronic antigen challenge. Repeated administration
of dexamethasone and Ro 20-1724 with each OvA exposure attenuated all of the
chronic inflammatory responses: early and late phase responses, hyperreactivity
and eosinophilia.
PMID- 9641583
TI - The video questionnaire: one approach to the identification of the asthmatic
phenotype.
PMID- 9641584
TI - Methods to assess and quantify BHR (bronchial hyperresponsiveness) in
epidemiological studies.
PMID- 9641585
TI - Problems and progress in measuring methacholine bronchial reactivity.
PMID- 9641586
TI - Early life markers of atopy and asthma.
AB - Since early intervention could modulate the natural course of atopic disease, the
availability of predictive markers is of considerable interest. As long as
specific genetic markers are not available, early IgE-responses (hen's egg)
together with a positive family history of atopy can be proposed as highly
specific and predictive markers, which could define subgroups as potential
candidates for secondary prevention.
PMID- 9641587
TI - Phenotype stability in asthma and atopy in childhood.
AB - The asthma phenotype can be described using a combination of the following:
symptom type, pattern and severity; markers of atopy; and measurement of
bronchial responsiveness. Because of the very nature of the disease, symptoms of
asthma are variable in both the short-and the long-term, and the natural history
of the disease is such that symptoms in an individual may evolve over time
through different patterns. Although atopy appears to be a life-long attribute
resulting from an early life switching to a TH2 immune response, the surrogate
markers of atopy each are subject to their own time-related determinants and
patterns of change with age. Bronchial responsiveness in childhood is neither
specific nor sensitive for asthma, and although showing good short-term
repeatability, can vary widely when measured over a period of months or years.
Stimuli for responsiveness testing should be chosen which can be inhaled safely
in high doses so as to allow an end point to be reached by as many subjects
within a population as possible, and individuals may have to be tested repeatedly
over time so as to avoid misclassification.
PMID- 9641588
TI - Phenotypic heterogeneity in asthma and allergy.
PMID- 9641589
TI - The relationship of parasites to asthma.
PMID- 9641590
TI - Phenotyping asthma patients for a gene mapping study in Finland.
PMID- 9641591
TI - Using genes and environments to define asthma and related phenotypes:
applications to multivariate data.
PMID- 9641592
TI - Use of cohorts with extensive longitudinal data in investigating the molecular
genetics of asthma.
AB - Recent studies have associated several chromosomal regions and specific
polymorphisms with asthma, atopy and airway hyperresponsiveness. Most of these
studies have been cross-sectional which substantially limits their power to
analyse genotype/phenotype associations. Asthma is a such a highly variable
condition that future genotype/phenotype studies should use longitudinal data.
Populations with extensive long-term longitudinal data will facilitate more
precise definition of phenotype and allow analysis of asthma's natural history.
Longitudinal information also means that each phenotypic attribute can be
quantified and considered with respect to age. Collecting longitudinal data
prospectively would be extremely expensive and take many years. Using existing
longitudinal data sets would clearly be much quicker and more economical, but
there are very few suitable data sets to be found. Studying a normal and an
asthmatic population is ideal and would provide complementary genotype/phenotype
information. This approach is a logical step to using the genotypic information
obtained from cross-sectional molecular genetic studies to more critically
establish the effect of genotype on phenotype.
PMID- 9641594
TI - The genetics of asthma. Maternal effects in atopic disease.
PMID- 9641593
TI - Approaches and issues in defining asthma and associated phenotypes map to
chromosome susceptibility areas in large Minnesota families. The Collaborative
Study for the Genetics of Asthma (CSGA).
AB - Evidence for linkage of asthma and its associated phenotypes with susceptibility
genes on chromosome 12 has been demonstrated in one group of Minnesota families.
The evidence is strong in affected sib pairs and weakens in analysis of the large
pedigrees. A second group of families provided little evidence for such linkage.
A discrepancy has been demonstrated in different families. This may be due to
several factors, including genetic heterogeneity and gene-gene, or gene
environmental interaction effects as well as the statistical power of the sample
population used.
PMID- 9641595
TI - Definition of asthma: possible approaches in genetic studies.
PMID- 9641596
TI - Using association studies to test for gene-environment interaction asthma and
other complex diseases.
PMID- 9641597
TI - The genetics of asthma. Candidate gene approaches: gene-environmental
interactions.
PMID- 9641598
TI - Pharmacogenetics of relevant targets in asthma.
PMID- 9641599
TI - Analytic options for asthma genetics.
AB - The analytic methods currently being used for the study of the genetics of asthma
have primarily focused on the evaluation of linkage by non-parametric methods as
applied to genome screen data in affected sibling pairs. Complexity in the
analysis of asthma genetics has been shown to occur at several levels, including
phenotypic definition (wide vs narrow criteria for asthma, including restriction
based upon multiple phenotypes) and joint analysis of asthma with associated
phenotypes. Alternative approaches that purport to treat asthma as a quantitative
trait (a 'score' or 'index') rather than as a qualitative (asthma, yes or no)
trait were presented, including the development of a 'Framingham Risk Score' for
asthma, a selection index, or a propensity score. While each of these
alternatives have interesting features, issues relating to estimation and
incorporation in a family structure have yet to be resolved. Nonetheless,
collection of a standard set of clinical data from multiple studies could be used
in a score to increase the power of genetic mapping studies for asthma.
PMID- 9641600
TI - Investigating the asthma phenotype.
PMID- 9641601
TI - Structure/function variants as candidate genes in asthma: linkage vs. association
for relevance.
PMID- 9641602
TI - The genetics of asthma. Implications of association studies in asthma.
PMID- 9641603
TI - The genetics of asthma. Quantitative scores for asthma and atopy.
PMID- 9641604
TI - Approaches to fine mapping in asthma.
PMID- 9641605
TI - The genetics of asthma. Mapping genes for complex traits in founder populations.
PMID- 9641606
TI - Approaches to meta analysis in genetic disorders.
PMID- 9641607
TI - Report of the Working Group on phenotype approaches.
PMID- 9641608
TI - Report of the Working Group on analytical methods.
PMID- 9641609
TI - Report of the Working Group on functional genetics/molecular approaches to asthma
genetics.
PMID- 9641610
TI - Evidence for a leptin-neuropeptide Y axis for the regulation of growth hormone
secretion in the rat.
AB - The obese gene (OB) product, leptin, has been shown to exert control on metabolic
processes such as food intake and body weight homeostasis, possibly through a
neuropeptide Y (NPY) neurotransmission. More recently, leptin has been shown to
control several neuroendocrine axes, modulating pituitary hormone secretions in
function of metabolic conditions. Since in the rat growth hormone (GH) secretion
is dependent upon prevailing metabolic conditions, and NPY has been shown to be
implicated in the feedback mechanisms of this hormone, we reasoned that leptin
could also exert control over GH secretion and we examined this hypothesis in
male rats submitted to a 3-day fast. Circulating leptin concentrations measured
by RIA abruptly fell to low values after 24 h of fasting and remained low
thereafter. Upon refeeding, leptin secretion regularly increased. As shown by
others, pulsatile GH secretion had disappeared after 3 days of fasting. Centrally
administered leptin (10 microg/day, i.c.v. infusion initiated at the beginning of
the fasting period) totally prevented the disappearance of pulsatile GH
secretion. No leak of centrally administered leptin to the general circulation
was observed. Infusing the same amount of leptin intracerebroventricularly to
rats receiving ad libitum feeding produced a severe reduction in food intake but
maintained a normal GH secretory pattern. In contrast, pair-fed rats, submitted
to the same food restriction, exhibited a marked reduction in GH secretion.
Hypothalamic NPY gene expression, estimated by Northern blot analysis, was
significantly increased in fasting rats, and decreased in leptin-treated, fasting
rats. In rats receiving ad libitum feeding, leptin treatment reduced NPY gene
expression, consistent with the observed reduction in food intake, whereas pair
fed animals logically exhibited increased NPY gene expression. In both situations
with reduced feeding, normal GH secretion was seen in leptin-treated animals
exhibiting low NPY gene expression, whereas decreased or abolished GH secretion
was seen in animals not receiving leptin and exhibiting increased NPY mRNA
levels. Interestingly, despite maintenance of normal GH secretion in leptin
treated, fasting rats, plasma IGF-I levels were low, as in vehicle-treated rats.
Indeed, hepatic gene expression for both GH receptor and IGF-I was markedly
reduced by fasting, and no correction was seen with leptin treatment. In summary,
the regulation of GH secretion, at least the changes linked with malnutrition,
appears to be dependent upon a leptin signal, perceived centrally, possibly
related to circulating levels of this new hormone. The present data suggest that
leptin can rescue normal pulsatile GH secretion by preventing the documented
inhibitory action of NPY on GH secretion.
PMID- 9641611
TI - Long-term inhibitory effects of somatostatin and insulin-like growth factor 1 on
growth hormone release by serum-free primary culture of pituitary cells from
European eel (Anguilla anguilla).
AB - To investigate the ability of hypothalamic and peripheral factors to directly
regulate growth hormone (GH) release in a primitive teleost, the European eel
(Anguilla anguilla L.), we used primary cultures of dispersed pituitary cells.
When cultured for 12 days in a serum-free medium, pituitary cells continuously
released large amounts of GH, which exceeded the initial cellular content.
Somatotropin-release inhibiting hormone (SRIH-14) dose-dependently inhibited GH
release (EC50 0.75 nM) up to a maximal inhibitory effect of 95%. No
desensitization of somatotropes to SRIH was observed over the 12 days of culture.
Use of receptor subtype-selective SRIH agonists suggests the existence on eel
somatotropes of SRIH receptor(s) related to the mammalian sst2/sst3/sst5 class
rather than to the sst1/sst4 class. Insulin-like growth factor 1 (IGF1) dose
dependently inhibited GH release (EC50 0.03 nM) up to a maximal inhibitory effect
of 85%, without desensitization. IGF1 and IGF2 were equipotent in inhibiting GH
release, whereas insulin was 1,000 times less active, suggesting the implication
of a receptor related to the mammalian IGF type 1 receptor. These results
indicate that eel somatotropes are active in vitro without any specific
additional factors, and suggest the existence of a dominant inhibitory control of
GH release in vivo. Two potential candidates for this chronic negative regulation
are a neurohormone, SRIH and a circulating factor, IGF1. These data underline the
early evolutionary origin of the molecular and functional SRIH-GH-IGF1
neuroendocrine axis in vertebrates.
PMID- 9641612
TI - Effects of dexamethasone and alprazolam, a benzodiazepine, on the stimulatory
effect of hexarelin, a synthetic GHRP, on ACTH, cortisol and GH secretion in
humans.
AB - Hexarelin (HEX) is a synthetic GHRP which acts on specific receptors at both the
pituitary and the hypothalamic level to stimulate GH release both in animals and
in humans. Like other GHRPs, HEX possesses also acute ACTH and cortisol-releasing
activity similar to that of hCRH. The mechanisms underlying the stimulatory
effect of GHRPs on hypothalamo-pituitary-adrenal (HPA) axis are still unclear,
although a CNS-mediated action has been demonstrated. In 6 normal healthy young
women (26-34 years) we studied the effects on ACTH and cortisol secretion of HEX
(2.0 microg/kg i.v. at 0 min) alone and preceded by dexamethasone (DEXA, 1 mg
p.o. at 23.00 h on the previous night) or alprazolam (ALP, 0.02 mg/kg p.o. at -90
min), a benzodiazepine which binds to GABA receptors and possesses CRH-mediated
inhibitory activity on HPA axis. ACTH and cortisol secretion after saline
administration as well as the GH response to HEX alone and preceded by DEXA or
ALP were also studied. HEX administration elicited an increase in ACTH (peak vs.
baseline, mean +/- SEM: 28.0 +/- 6.7 vs. 11.7 +/- 2.2 pg/ml, p < 0.05) and
cortisol secretion (162.6 +/- 15.0 vs. 137.7 +/- 12.6 microg/l, p < 0.05). DEXA
pretreatment strongly inhibited basal ACTH (3.2 +/- 0.7 pg/ml, p < 0.01) and
cortisol levels (11.3 +/- 2.5 microg/l, p < 0.001) and abolished the ACTH and
cortisol responses to HEX (3.6 +/- 0.9 pg/ml, p < 0.01 and 10.7 +/- 2.0 microg/l,
p < 0.001), respectively. On the other hand, ALP pretreatment did not
significantly modify basal ACTH (7.9 +/- 2.0 pg/ml) and cortisol levels (127.6 +/
14.5 microg/l) but abolished the HEX-induced ACTH and cortisol secretions (8.6
+/- 2.4 pg/ml, p < 0.05 and 111.0 +/- 6.0 microg/l, p < 0.05), respectively. ACTH
and cortisol levels after HEX when preceded by ALP overlapped with those recorded
during saline. HEX induced a clear GH response (peak at 15 min vs. baseline: 65.5
+/- 20.5 vs. 2.2 +/- 0.7 microg/l, p < 0.03) which was blunted by ALP (peak at 15
min: 21.5 +/- 5.5 microg/l, p < 0.05) while it was not modified by DEXA
pretreatment (78.7 +/- 7.6 microg/l). In conclusion, our present data demonstrate
that the ACTH- and cortisol-releasing effect of HEX is abolished by either
dexamethasone or alprazolam, a benzodiazepine, which is even able to blunt the GH
releasing activity of the hexapeptide. These findings suggest that, in
physiological conditions, the stimulatory effect of GHRPs on HPA axis is
sensitive to the negative glucocorticoid feedback and could be mediated by
GABAergic mechanisms; the latter seem also involved in the GH-releasing activity
of GHRPs.
PMID- 9641613
TI - Growth hormone, fatigue, poor sleep, and disability in HIV infection.
AB - Poor sleep, daytime fatigue, and loss of cognitive ability exist during all
stages of HIV infection, worsening with disease progression. These symptoms
contribute to disability and poor quality of life. Data from several research
groups support a role of somnogenic inflammatory process peptides elevated in HIV
infection, e.g. TNF alpha. Though the literature is in conflict regarding an
effect of HIV infection on growth hormone (GH) secretion, GH axis dysregulation
and treatment with GH may be important in HIV infection, e.g. in the wasting
syndrome. It has long been known that GH varies with changes in sleep. The
hypothesis tested in the current study was that the relationship between delta
frequency (0.5-4.0 Hz) sleep EEG amplitude (square root of power from frequency
analysis) and GH secretion would differ between HIV positive (HIV+) and HIV
negative (HIV-) subjects. In 14 subjects (6 HIV+ and 8 HIV-, none with current or
past AIDS-defining illness) a linear relationship change across the night's sleep
was found in the coupling between delta frequency sleep EEG amplitude and GH
secretion. The phase coupling change was in opposite directions in HIV+ versus
HIV- subjects. This difference supports the hypothesis that the brain-based
coordination of sleep and sleep-related physiology deteriorates early in HIV
infection, and that GH dysregulation may contribute to this sleep pathology.
PMID- 9641614
TI - Dehydration-induced renin secretion: involvement of histaminergic neurons.
AB - Renin secretion is controlled locally in the kidneys as well as via central
neuronal mechanisms. The neuronal mechanisms are not fully understood but may
involve the neurotransmitter histamine (HA) since centrally infused HA stimulates
renin secretion. This, however, does not prove that HA is of any physiological
importance for the regulation of renin secretion. Dehydration is a physiological
stimulus of renin secretion and, therefore, we studied the possible role of
hypothalamic histaminergic neurons in dehydration-induced renin secretion in
conscious male rats. In addition, we expanded on our previous investigations of
HA-induced renin secretion. Twenty-four hours of dehydration induced a 3-fold
increase in plasma renin activity (PRA). Pretreatment with the HA synthesis
inhibitor alpha-fluoromethylhistidine inhibited the dehydration-induced PRA
secretion by 80% whereas pretreatment with the H1 receptor antagonist mepyramine
(MEP) or the H2 receptor antagonist ranitidine (RAN) inhibited the PRA response
to dehydration by approximately 40%. In euhydrated control rats, none of the HA
blocking agents had any significant effect on basal PRA secretion. Central
administration of HA stimulated PRA almost 2-fold and the maximum concentration
of PRA was reached after 15 min. Pretreatment with the H1 receptor antagonist MEP
or the H2 receptor antagonist RAN totally inhibited the HA-induced PRA secretion.
We conclude that HA activates renin secretion via H1 and H2 receptors and that HA
seems to be a physiological mediator of dehydration-induced renin secretion via
activation of H1 and H2 receptors. The effect is probably indirect and may among
others involve the catecholaminergic and serotonergic systems.
PMID- 9641615
TI - Selective inhibition of magnocellular vasopressin neurons by hypoosmolality:
effect on histamine- and stress-induced secretion of adrenocorticotropin and
prolactin.
AB - We investigated the effect of selective inhibition of magnocellular arginine
vasopressin (AVP) and oxytocin neurons on histamine (HA)- and restraint-stress
induced adrenocorticotropin (ACTH) and prolactin (PRL) secretion in conscious
male rats. The inhibition of magnocellular neurons was obtained by inducing
chronic hypoosmolality via continuous exposure of the rats to the AVP V2 receptor
agonist 1-deamino(8-D-arginine)vasopressin (DDAVP) which was released from
osmotic pumps implanted subcutaneously. In DDAVP-treated rats, plasma osmolality
and sodium concentration were 273 mosm/l and 130 mmol/l, respectively. In control
rats, the corresponding values were 291 mosm/l and 139 mmol/l. HA (270 nmol)
administered intracerebroventricularly or 5 min of restraint stress stimulated
ACTH and PRL secretion 4- to 11-fold in normoosmolar rats. In hypoosmolar rats,
the HA-induced ACTH response was inhibited more than 40% whereas the restraint
stress-induced ACTH response was unaffected. Conversely, the PRL response to HA
in hypoosmolar rats was unaffected whereas the PRL response to restraint stress
was inhibited by 40%. In summary, chronic hypoosmolality inhibits HA-induced ACTH
and restraint-stress-induced PRL secretion indicating involvement of
magnocellular AVP in these responses.
PMID- 9641616
TI - Dopamine produced by the stomach may act as a paracrine/autocrine hormone in the
rat.
AB - Dopamine (DA) has been suggested to be a protective factor in the
gastrointestinal tract but neither a source of DA nor its exact targets of action
have been identified. In this study, we demonstrate high levels of DA (and DOPA)
which persist after chemical sympathectomy in the gastric juice of rats.
Immunostaining and in situ hybridization histochemistry reveal the presence of
tyrosine hydroxylase (TH), DA transporter and vesicular monamine transporters in
the acid-producing parietal cells. Like DA, TH enzyme activity remains after
chemical sympathectomy. We also demonstrate active reuptake and storage of DA
that indicates a regulated release of this neurohormone from parietal cells. DA
D1b receptor mRNA is the most abundant DA receptor subtype in gastric and
duodenal epithelium. Therefore, we suggest that selective DA D1b receptor
agonists may be useful adjuncts in the treatment of duodenal and gastric ulcers.
Gastric epithelia possess the hallmarks of functional DA neuroendocrine cells,
suggesting that DA has an important role in self-protective mechanisms of the
gastrointestinal tract. These findings should allow elucidation of DA role in
normal and disease states in the stomach and duodenum.
PMID- 9641617
TI - Effect of melatonin on 24-hour rhythms of ornithine decarboxylase activity and
norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen
of young and aged rats.
AB - Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected
with mycobacterial Freund's adjuvant to produce an inflammatory disease of the
joints and were studied the day before, and on days 6, 12 and 18 after injection.
At every postinjection interval examined, old rats had significantly lower
circadian amplitudes of pineal melatonin content. On day 18 of arthritis
development, decreased levels of pineal melatonin were also seen in young rats. A
second study, carried out 18 days after the injection of Freund's complete
adjuvant and after 17 daily injections of 10 or 100 microg of melatonin in the
evening, indicated that melatonin treatment restored the inflammatory response in
old rats (assessed plethysmographically in hind paws) to the level found in young
animals. In young rats, an inflammation-promoting effect of 100 microg melatonin
could be demonstrated. As a consequence of the immune reaction, submaxillary
lymph node and splenic ornithine decarboxylase activity (an index of lymph cell
proliferation) augmented significantly, with acrophases of 24-hour rhythms in the
afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of
ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection
generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase
activity (a presynaptic adrenergic marker) reached maximal values during early
night hours while maximal values of [3H]acetylcholine synthesis (a presynaptic
cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and
mesor of these rhythms were lowest in old rats, an effect generally counteracted
by melatonin treatment. The results suggest that inflammation is accompanied by
an age-dependent, significant depression of pineal melatonin synthesis during
adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of
immune cell proliferation and autonomic activity in lymph nodes and spleen. These
effects are counteracted by injection of melatonin, mainly in old rats.
PMID- 9641618
TI - In vivo degradation of a poly(propylene fumarate)/beta-tricalcium phosphate
injectable composite scaffold.
AB - This study was designed to investigate the in vivo biodegration and
biocompatibility of a poly(propylene fumarate) (PPF)-based orthopedic
biomaterial. The effects of varying the PPF to N-vinyl pyrrolidinone ratio and
PPF to beta-tricalcium phosphate content were studied. The composite mechanical
properties and local tissue interactions were analyzed over 12 weeks. An initial
increase in both compressive modulus and strength was seen for composite
formulations that incorporated beta-tricalcium phosphate. The samples
incorporating a higher PPF to N-vinyl pyrrolidinone ratio reached a maximal
compressive strength of 7.7 MPa and a maximal compressive modulus of 191.4 MPa at
3 weeks. The lower PPF to N-vinyl pyrrolidinone ratio samples gained a maximum
compressive strength of 7.5 MPa initially and a compressive modulus of 134.0 MPa
at 1 week. At 6 weeks, all samples for formulations incorporating beta-tricalcium
phosphate crumbled upon removal and were not mechanically tested. Samples that
did not incorporate beta-tricalcium phosphate were very weak and insufficient for
bone replacement at the 4-day time point and beyond. Tissue interactions resulted
in a mild inflammatory response at the initial time points and mature fibrous
encapsulation by 12 weeks.
PMID- 9641619
TI - Cyclic anhydride ring opening reactions: theory and application.
AB - The development of a zero net shrinkage dental restorative material based upon a
polymer-bioactive-glass composite requires a second-phase material that expands.
This study details the mechanisms of organic cyclic anhydride ring expansion via
hydrolysis. Six cyclic anhydrides were used to represent potential side groups,
each of which could be an expanding phase or component. Maleic, 4META,
tetrahydrophthalic, norbornene, itaconic, and succinic anhydrides were modeled
using the Austin method (AM1), a semi-empirical molecular orbital method. The
reaction pathways were determined for the anhydride ring opening reaction to form
an acid for each case. The activation barriers (Ea) for the ring openings were
found from the transition state geometries wherein only one imaginary eigen value
in the vibration spectrum existed (a true saddle point). In each case the
reaction pathway included the hydrogen bonding of a H2O molecule to the ring,
weakening of the C-O bridging bonds of the ring, and, finally, the dissociation
of the H2O, forming two carboxyl groups and opening the ring. The activation for
the ring openings are +34.3, +36.9, +40.6, +43.1, +45.9, and +47.7 kcal/mol,
respectively. The volumetric expansion of the anhydrides was estimated based upon
the dilation of C-O-C atomic distances. The dimensional change was found to be
24.0%, 24.0%, 19.1%, 20.3%, 20.8%, and 17.9% for the anhydride rings,
respectively. Finally, it was found that a linear correlation exists between the
cyclic anhydride C-O asymmetric rocking (as-v) vibration and the activation
energy (Ea) for hydrolysis to an acid. This may be used as an experimental
indicator of a cyclic anhydride's activity.
PMID- 9641620
TI - Characterization of soluble, salt-loaded, degradable PLGA films and their release
of tetracycline.
AB - A local drug delivery system has been designed to release tetracycline over a
period of 30 days from poly (lactide-co-glycolide) films. Incorporation of either
soluble salt excipients or low molecular weight polymeric species has been found
to modulate the release kinetics of the system. The following research describes
the fabrication of the delivery system, monitors tetracycline release from the
system, and fully characterizes the degradation of the polymer films via scanning
electron microscopy, gel permeation chromatography, differential scanning
calorimetry, Fourier-transform infrared spectroscopy, and X-ray diffraction
techniques. Results show that the modulation via use of salts occurs without
changing the inherent degradation rate of the system. We suggest that this
phenomenon may be due to the increased amount of swelling and uptake of buffer by
the films loaded with soluble salt. Uptake, therefore, may be creating
microscopic pores that permit further diffusion of tetracycline from the polymer
matrix as well as allow the free monomers to leave the system, thereby preventing
autocatalysis within the system.
PMID- 9641621
TI - Laminin-5 coating enhances epithelial cell attachment, spreading, and
hemidesmosome assembly on Ti-6A1-4V implant material in vitro.
AB - Enhancement of epithelial cell attachment to laminin-5-coated titanium alloy (Ti
6Al-4V) implant material was evaluated in vitro. Protein analysis showed that Ti
6Al-4V has a high affinity for laminin-5 and adsorbed significantly more laminin
5 than laminin-1. DNA analysis showed that laminin-5 enhanced attachment of
normal human epidermal keratinocytes (NHEK) to Ti-6Al-4V significantly more than
did laminin-1 or uncoated controls. The effect of passivation on laminin-5
adsorption and activity on Ti-6Al-4V also was evaluated. Passivation had no
significant effect on the amount of protein adsorbed; however, AFM, ESCA, and ToF
SIMS analyses suggested that passivation affects the conformation of adsorbed
laminin-5. Although laminin-5 coating significantly enhanced rapid attachment of
epithelial cells to both passivated and unpassivated Ti-6Al-4V, surface area
measurements showed that cells spread on laminin-5-coated passivated Ti-6Al-4V
covered a significantly larger surface area than cells spread on laminin-5-coated
unpassivated samples. TEM analysis showed that cells formed significantly more
hemidesmosomes on the surface of laminin-5 coated passivated than on the surface
of laminin-5 coated unpassivated titanium alloy. The enhancement of rapid cell
attachment, spreading, and hemidesmosome assembly on laminin-5-coated passivated
samples may reflect better integration between epithelial cells and titanium
alloy and thus may be predictive of long-term implant stability.
PMID- 9641622
TI - Histomorphometrical and mechanical evaluation of titanium plasma-spray-coated
implants placed in the cortical bone of goats.
AB - The aim of this study was to investigate the biological and mechanical response
of bone to titanium plasma-sprayed implants of different roughnesses. Three types
of titanium plasma-spray coating were applied to beam-shaped implants: Ti2, Ti3,
and Ti4, with a Ra of 16.5, 21.4, and 37.9 microm, respectively. An Al2O3 grit
blasted implant (Ti-un) with a Ra of 4.7 microm was used as a control. In total,
72 implants were inserted in the tibial cortical bone of nine adult female goats.
These implants were evaluated histologically and mechanically 3 months after
implantation. At the end of the experiment, of the 72 inserted implants, two
implants (one Ti2 and one Ti4) were lost. Histological evaluation of the other
retrieved implants revealed a uniform bone reaction for all implants. The
unloaded plasma-spray coatings showed no signs of delamination at the implant
coating interface. Occasionally, particles of the Ti4 coating broke free and were
found near the implant. Histomorphometry revealed no difference in bone contact
for the different implants (P > 0.05). Furthermore, the push-out test showed no
significant difference (P > 0.05). Linear regression showed no interaction
between the push-out values and the roughness values (r = 0.5). On the basis of
these results, it may be concluded that the used surface roughnesses did not lead
to differences in bone response or mechanical attachment strength in goat
cortical bone.
PMID- 9641623
TI - Anticoagulant activity of dextran derivatives.
AB - Carboxymethyl dextran benzylamide sulfonate/sulfates (CMDBS) are synthetic
polysaccharides with anticoagulant activity. We synthesized eight different
highly substituted CMDBS and one CMDSu. We studied both their anticoagulant
activity and the catalysis of thrombin (T) inhibition by heparin cofactor II
(HCII) and antithrombin (AT) in the presence of these dextran derivatives
relative to heparin and dextran sulfate (DXSu). The anticoagulant activity of
CMDBS was due both to direct thrombin inhibition and to catalysis of thrombin
inhibition by HCII. The anticoagulant and catalytic activities of CMDBS were
related mainly to their molecular weight and sulfate content. The interaction of
the dextran derivatives with thrombin does not involve the active site of the
enzyme. A kinetic study showed that all the CMDBS exhibited higher affinity for
thrombin than heparin did but lower affinity than DXSu did, suggesting that the
benzylamide and sulfate groups potentiate the interaction between the dextran
derivatives and thrombin. This study shows that the mechanism by which the
dextran derivatives inhibit thrombin is original and is related to preferential
interaction with thrombin; this both inhibits the clotting activity of the enzyme
and increases the reaction rate of thrombin inhibition by HCII.
PMID- 9641624
TI - A multidirectional motion pin-on-disk wear test method for prosthetic joint
materials.
AB - A realistic pin-on-disk wear test method for prosthetic joint materials has been
developed. The new method, called circularly translating pin-on-disk (CTPOD),
yields wear rates and wear mechanisms similar to those observed in retrieved
polyethylene acetabular cups. In the established methods, where a polyethylene
specimen slides against a unidirectionally rotating, or reciprocating, metallic
or ceramic counterface, the wear rate typically is two orders of magnitude too
low. In the present study, also, the reciprocator gave negligible wear. In the
CTPOD method, considerable wear occurs because the direction of sliding rotates
relative to the polyethylene pin, hence, the molecular orientation effect of
polyethylene is avoided.
PMID- 9641625
TI - Electrical properties of glucose-sensitive hydrogels: swelling and conductivity
relationships.
AB - The electrical characteristics of a glucose-sensitive polymeric hydrogel have
been studied. The hydrogel matrices were prepared by radical polymerization of
solutions containing 2-hydroxyethyl methacrylate, N,N-dimethyl aminoethyl
methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and
glucose oxidase. The hydrogels displayed faster and higher swelling rates for
lower levels of a crosslinking agent. Electrical conductivity was found to be a
sensitive measurement of the state of the swelling. A simple model that relates
hydrogel swelling and conductivity has been proposed.
PMID- 9641626
TI - Morphology of chemically crosslinked ultrahigh molecular weight polyethylene.
AB - Morphological characterization of chemically crosslinked ultrahigh molecular
weight polyethylene was performed by differential scanning calorimetry and
scanning electron microscopy. The lamellar thickness of nascent UHMWPE inferred
from DSC endotherms showed a very broad distribution, which was reduced
significantly after melting and recrystallizing in DSC. Peroxide crosslinking
further reduced the lamellar thickness distribution compared to uncrosslinked
samples. After gamma-irradiation, a slowly cooled peroxide-free sample showed a
greater increase in lamellar thickness distribution. Examination of the
morphology of freeze-fractured surfaces by SEM showed that a slowly cooled
peroxide-free UHMWPE exhibited a rougher fracture while chemically crosslinked
samples showed a smoother fracture. After compression molding at 300 degrees C
for 2 h, the grain boundaries between particles disappeared for all UHMWPE
samples, indicating a complete fusion of the original flakes.
PMID- 9641627
TI - Carbonate substitution in precipitated hydroxyapatite: an investigation into the
effects of reaction temperature and bicarbonate ion concentration.
AB - Carbonate substitution in the apatite crystal lattice can occur in either the
hydroxyl or the phosphate sites, designated as A or B type, respectively, and
previous investigations generally have described precipitated carbonate
hydroxyapatite as being B type on the basis of infra red and X-ray data. This
paper documents the effects of two precipitation variables, namely temperature
and bicarbonate ion concentration, on the morphology, phase composition, and
calcium, phosphorus, and carbon contents of precipitated carbonate
hydroxyapatite. Variations in both temperature and bicarbonate concentration
could yield either acicular or spheroidal crystals. X-ray diffraction and infra
red spectroscopy indicated the presence of carbonate in the A site for low
carbonate contents (< 4 wt%), and at higher carbonate contents (> 4 wt%), the
carbonate was located predominantly in the B site. On the basis of these
observations and chemical analyses, a new AB carbonate substitution mechanism is
proposed that better describes the experimental data than the B-type models used
previously.
PMID- 9641628
TI - Si-Ca-P xerogels and bone morphogenetic protein act synergistically on rat
stromal marrow cell differentiation in vitro.
AB - This study describes a novel bioactive xerogel glass as a carrier for bone
morphogenetic protein (BMP) and the value of this carrier in terms of stimulating
osteogenic activity of rat stromal marrow cells in vitro. These cells were seeded
onto the surface of xerogel glass disks with BMP either incorporated in the
glass, adsorbed to the surface of the glass, or added to the culture media and
then compared to cells on glass with no added BMP or to cells on tissue culture
plastic (TCP) with and without BMP. Cells were cultured for 6 and 10 days and
examined for total DNA, alkaline phosphatase activity, and osteocalcin and total
protein production. Stromal cell differentiation, as measured by alkaline
phosphatase activity and osteocalcin synthesis was most increased when the BMP
was incorporated or adsorbed onto the xerogel glass. Cells on xerogel glass
without BMP were more differentiated than cells grown on plastic with BMP,
thereby demonstrating the additive effect of a bioactive substrate and BMP on
osteoblastic cell differentiation. These data indicate that xerogel glass effects
differentiation of cells with osteogenic potential and that it can serve as a
delivery vehicle for BMP.
PMID- 9641629
TI - Fibronectin adsorption, conformation, and orientation on polystyrene substrates
studied by radiolabeling, XPS, and ToF SIMS.
AB - Protein adsorption is widely studied by a variety of techniques, but there still
is little known about protein orientation and conformation after adsorption. This
probably is due to the large number of parameters involved, such as the
characteristics of the surface and the structure of the protein. In this study,
the adsorption of fibronectin was investigated with three different techniques:
radiolabeling, X-ray photoelectron spectroscopy (XPS), and time-of-flight
secondary ion mass spectrometry (ToF SIMS) on polystyrene and oxidized
polystyrene. The first two techniques have been widely used to study protein
adsorption, allowing us to determine the amount of protein adsorbed on each
surface. The ToF SIMS, however, is a technique just emerging for the study of
protein adsorption. This study confirms its utility since ToF SIMS is found to be
sensitive to the protein orientation and/or conformation at the surface. Indeed,
the ToF SIMS peaks characteristic of the protein show differences in their
reduced intensity between the two substrates. These differences, which are not
detected by XPS, are attributed to different orientations and/or conformations of
the protein.
PMID- 9641630
TI - In vitro cellular responses to bioerodible particles loaded with recombinant
human bone morphogenetic protein-2.
AB - Porous 50:50 poly(d,l lactide-co-glycolide) microspheres containing varying
amounts of "free" recombinant human bone morphogenetic protein-2 (rhBMP-2) were
evaluated for their ability to induce/enhance expression of osteoblastic
characteristics by pluripotent mesenchymal cells in vitro. "Free" protein (Fp) is
defined as protein present on the surface and within the porous matrix of the
microspheres. Four preparations of bioerodible particles (BEP) were used: blank-
without rhBMP-2; low Fp--24 microg of free rhBMP-2 per g of particles; medium Fp-
403 microg/g; and high Fp--884 microg/g. C3H10T1/2 cells (C3H) and bone marrow
stromal cells (BMC) were cultured with 1 mg of BEP for up to 4 weeks, and cell
growth and expression of osteogenic responses were determined weekly. For both
cell types, control cultures (neither BEP nor rhBMP-2) and cultures with blank
BEP exhibited no or minimal osteoblastic characteristics. Compared to control and
blank BEP cultures, C3H cells responded to particles having medium and high
amounts of free rhBMP-2 with increased cell growth and alkaline phosphatase
activity, but osteocalcin secretion and mineralization were not markedly
influenced. Low Fp BEP enhanced only the alkaline phosphatase activity of C3H
cells. In contrast, although growth was not affected, rhBMP-2-loaded BEP
increased alkaline phosphatase activity, osteocalcin secretion, and
mineralization in BMC cultures in a dose-dependent manner (i.e., blank < low <
medium < high Fp).
PMID- 9641631
TI - An immunoelectron microscopic localization of noncollagenous bone proteins
(osteocalcin and osteopontin) at the bone-titanium interface of rat tibiae.
AB - This study was designed to investigate by postembedding immunogold method the
localization and distribution of osteocalcin (Ocl) and osteopontin (Opn) at the
bone-titanium interface in rat tibiae 14 and 28 days postimplantation to
determine which bone proteins are present at this interface. Both proteins were
widely distributed on the newly formed bone and accumulated predominantly in the
region of bone close to the titanium, in electron-dense patches in the bone, and
at the osteocytic lacunae. Collagenous osteoid showed little or no labeling for
either Ocl or Opn. An amorphous zone (20-50 nm) was interposed between the
titanium and interfacial slender cells, osteoid, or bone, and was labeled
strongly for Ocl but only weakly for Opn. Furthermore, a second electron-dense
layer, the lamina limitans, which faces the titanium, was labeled strongly for
Opn but weakly for Ocl. Ocl as a marker protein of osteoblasts was sometimes
found in the granules and vesicles of the interfacial cells and extracellularly
in their intercellular spaces, close to the titanium. However, Opn was not
detected in any granules. This is the first report to show that the amorphous
zone contains large amounts of Ocl and small amounts of Opn, and that bone
contacts titanium through this Ocl-rich amorphous zone. Furthermore, it is
suggested that the interfacial cells seem to be osteoblasts, and that Ocl in the
amorphous zone is produced and secreted by these cells and functions with Opn as
a regulator of the mineralization front close to the titanium, and as a mediator
of cell-matrix and matrix-matrix/mineral adhesion along the titanium.
PMID- 9641632
TI - Surface analysis of human plasma fibronectin adsorbed to commercially pure
titanium materials.
AB - Protein binding on metallic implant surfaces, such as titanium, is governed by
the physico-chemical nature of the metallic surface. Human plasma fibronectin
(HPF) is an important matrix glycoprotein that mediates cell and protein
attachment to each other or to the extracellular matrix present during wound
healing. The objective of this study was to investigate the adsorption of HPF
onto polished commercially pure titanium (cpTi) by using atomic force microscopy
(AFM) and electron spectroscopy for chemical analysis (ESCA) and to measure the
resultant surface contact angle before and after HPF binding. Two types of cpTi
disks, one highly polished in our laboratory (HSS) and one commercially prepared
(31), were reacted with HPF solutions of varying concentrations (1 microg/mL-10
ng/mL). ESCA survey spectra of samples coated with 1 microg/mL of fibronectin
showed an increase in organic nitrogen and carbon compared with uncoated
controls. Contact angle measurements of HSS and 31 cpTi disks showed no
significant difference in average contact angle (36.3 degrees +/- 3.5 and 39.1
degrees +/- 3.1) despite differences in local root mean square (RMS) surface
roughness (4.45 +/- 0.46 nm and 22.37 +/- 4.17 nm) as measured by AFM. Images
obtained by AFM showed that 31 specimens were more irregular, with large parallel
polishing grooves. Adsorbed HPF appeared in a globular form with an average
length of 16.5 +/- 1.0 nm, a height of 2.5 +/- 0.5 nm, and a width of 9.6 +/- 1.2
nm. Fibronectin coating on both HSS and 31 cpTi specimens resulted in a
significant increase in hydrophobicity compared to uncoated specimens. These
results indicate the significance of HPF on cpTi and may explain how cpTi
implants function in situ.
PMID- 9641633
TI - The aortic valve microstructure: effects of transvalvular pressure.
AB - We undertook this study to establish a more quantitative understanding of the
microstructural response of the aortic valve cusp to pressure loading. Fresh
porcine aortic valves were fixed at transvalvular pressures ranging from 0 mmHg
to 90 mmHg, and small-angle light scattering (SALS) was used to quantify the
gross fiber structure of the valve cusps. At all pressures the fiber-preferred
directions coursed along the circumferential direction. Increasing transvalvular
pressure induced the greatest changes in fiber alignment between 0 and 1 mmHg,
with no detectable change past 4 mmHg. When the fibrosa and ventricularis layers
of the cusps were re-scanned separately, the fibrosa layer revealed a higher
degree of orientation while the ventricularis was more randomly oriented. The
degree of fiber orientation for both layers became more similar once the
transvalvular pressure exceeded 4 mmHg, and the layers were almost
indistinguishable by 60 mmHg. It is possible that, in addition to retracting the
aortic cusp during systole, the ventricularis mechanically may contribute to the
diastolic cuspal stiffness at high transvalvular pressures, which may help to
prevent over distention of the cusp. Our results suggest a complex, highly
heterogeneous structural response to transvalvular pressure on a fiber level that
will have to be duplicated in future bioprosthetic heart valve designs.
PMID- 9641634
TI - Tissue reactions to bacteria-challenged implantable leads with enhanced infection
resistance.
AB - Tissue reactions to implantable pacemaker leads were investigated in an early
infection model in rabbits. Both standard leads and surface-modified leads were
used. The surface modification technique was applied to achieve controlled
release of the antibiotic gentamicin. The insulating polyurethane tubing material
of the leads was provided with an acrylic acid/acrylamide copolymer surface graft
and then loaded with gentamicin. Implantation periods varied from day 4, to week
3 1/2, to week 10. We investigated tissue reactions in the absence of an
infectious challenge and also the efficacy of surface-modified leads in
preventing infection after challenge with Staphylococcus aureus was evaluated. It
was demonstrated that the applied surface modification did not induce adverse
effects although during early postimplantation an increase in infiltration of
granulocytes and macrophages and wound fluid and fibrin deposition were observed.
After bacterial challenge, standard leads were heavily infected at each
explantation period, denoted by abscesses, cellular debris, and bacterial
colonies. In contrast, little or no infection was observed, either
macroscopically or by bacterial cultures, with the surface-modified leads.
Microscopy showed little evidence of the bacterial challenge, and that primarily
at day 4. It was concluded that the applied surface modification demonstrated
enhanced infection resistance and thus represents a sound approach to the battle
against infectious complications with biomaterials.
PMID- 9641635
TI - In vitro biocompatibility assessment of a nickel-titanium alloy using electron
microscopy in situ end-labeling (EM-ISEL).
AB - Shape memory nickel-titanium (NiTi) alloys are potential candidates for
biomedical applications. However, their equiatomic composition (50 wt% Ni) is
controversial, and concerns have been raised about their biocompatibility level
because of the carcinogenicity potential. The relative in vitro genotoxicity of
NiTi therefore was evaluated and compared to commercially pure titanium (cpTi),
316L stainless steel (SS 316L), and positive and negative controls. To do so,
human peripheral blood lymphocytes were cultured in semiphysiological medium that
previously had been exposed to the biomaterials. The electron microscopy in situ
end-labeling (EM-ISEL) assay then was performed in order to provide
quantification of in vitro chromatin DNA single-stranded breaks (SSBs).
Chromosomes and nuclei were harvested and exposed to exonuclease III, which
amplifies DNA lesions at 3' ends of breaks. After random priming, incorporation
of biotin-dUTP was labeled by immunogold binding, which then was detected using
electron microscopy. Cellular chromatin exposed to the positive control
demonstrated a significantly stronger immunogold labeling than when it was
exposed to NiTi, cpTi, SS 316L extracts, or the untreated control. Moreover, gold
particle counts, whether in the presence of NiTi, cpTi, or the negative control
medium, were not statistically different. NiTi genocompatibility therefore
presents promising prescreening results towards its biocompatibility approval.
PMID- 9641636
TI - Analysis of in vitro reaction layers formed on Bioglass using thin-film X-ray
diffraction and ATR-FTIR microspectroscopy.
AB - Fourier transform infrared spectroscopy and thin-film X-ray diffraction (TF-XRD)
techniques were used to analyze the inorganic carbonate apatite (CA) layer
developed on a bioactive glass (45S5 type Bioglass) in an in vitro environment.
The C-O and P-O vibrational modes appeared on the bioactive glass surface
following immersion in the simulated body fluid solution. Initially, the C-O and
P-O peaks increased with immersion time as crystallization of CA phase
progressed. The TF-XRD confirmed that the deposited layer was apatite,
crystallographically. Furthermore, evidence of preferred orientation in the 001
direction was seen, indicated by very strong 002 reflection. With time, the
crystal growth became more random and the intensity of the 002 reflection
decreased.
PMID- 9641637
TI - Application of FT-IR microspectroscopy to the study of an injectable composite
for bone and dental surgery.
AB - Hydroxypropylmethylcellulose (HPMC) of high-viscosity grade is used as a ligand
for a bioactive calcium phosphate ceramic (the filler) in a ready-to-use
injectable sterilized biomaterial for bone and dental surgery. Application of
physico-chemical methods such as XPS, NMR, or Raman spectroscopy encounters
difficulties when used to study such a multiphased material. This paper reports
on the application of FT-IR microspectroscopy (FT-IRM) for the investigation of
inorganic and organic phases of the rough composite and separated phases obtained
by mechanical or chemical extraction methods. A comparison of FT-IRM with the
conventional KBr pellet method was made and indicates that the macro and micro FT
IR methods are complementary: the former revealed new chemical groups not
visualized with the KBr method whereas the latter detected the major compound of
the blend. FT-IR microspectroscopy was revealed to be a powerful method of
analysis that is complementary to other existing spectroscopic methods. Moreover,
it is expected to be a useful tool in the study of biomaterials in biological
samples.
PMID- 9641638
TI - Anti-nuclear and anti-histone auto-antibodies in autoimmune disease.
PMID- 9641639
TI - Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune
hepatitis.
PMID- 9641640
TI - Antipyrine clearance in chronic and neoplastic liver diseases: a study of 518
patients.
AB - Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve
of the liver. It is well known that metabolism of this drug is impaired in
subjects with acute hepatitis or cirrhosis, but conflicting data have been
reported regarding patients with chronic postinfectious hepatitis or liver
cancer. We studied conventional liver-function parameters and antipyrine
metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one
patients had liver metastases (various primaries). Based on the number and size
of lesions, the hepatic involvement was considered minimal in 47 and massive in
54 (groups B1 and B2, respectively). One hundred and two had chronic active
hepatitis (CAH); 51 patients with histological evidence of fibrosis/early
cirrhosis and 51 patients were without histological evidence of fibrosis/early
cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the
remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control
group was composed of 103 subjects with healthy livers (group A). Antipyrine
clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg)
was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min
per kg), and both values were significantly lower than that found in CAH patients
without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance
in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to
that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and
cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of
impairment. Antipyrine clearance was positively correlated with serum albumin (r2
= 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups,
except those with liver metastases. In patients with CAH, the presence of
fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of
impairment in groups with liver metastases suggests that the functional hepatic
reserve is maintained even in the presence of massive neoplastic invasion.
PMID- 9641641
TI - Case report: A hepatocellular carcinoma metastasis in the distal pancreas.
AB - Hepatocellular carcinoma is a highly malignant neoplasm. Extrahepatic metastases
are found in 64% of patients with hepatocellular carcinoma. The lungs, regional
lymph nodes, kidney, bone marrow and adrenals are common sites of metastases.
Pancreatic metastases are not common (<5%). A case report of a hepatocellular
carcinoma with a metastasis in the distal pancreas is presented. A resection of
the primary tumour and metastasis was carried out with the patient still alive 16
months after resection. This case illustrates that hepatic resection for
hepatocellular carcinoma with a single local metastasis can be reasonably
considered although a cure has not been established.
PMID- 9641642
TI - Case report: Steatonecrosis in the upper abdomen following transcatheter arterial
embolization for hepatocellular carcinoma.
AB - A 66-year-old female with liver cirrhosis was treated by transcatheter arterial
embolization (TAE) for a small hepatocellular carcinoma. She developed
steatonecrosis with tenderness which occurred in the upper abdomen after TAE. The
hepatic falciform artery from the middle hepatic artery was detected by
arteriography. Necrosis in the upper abdomen was considered to be due to
ischaemic changes caused by micromaterials for embolization of this artery,
injuries of hepatic arterial endothelia slowly caused by carcinostatics, and
chemotoxicity. It was considered that such complication as observed in this
patient should be taken into consideration when performing TAE.
PMID- 9641643
TI - Clinical significance of serum auto-antibodies in Chinese patients with chronic
hepatitis C: negative role of serum viral titre and genotype.
AB - Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA)
have been reported in 10-66% of patients with chronic hepatitis C virus (HCV)
infection from Western countries. However, the mechanism involved in this
immunological disorder is still unknown. This study was carried out to evaluate
the prevalence and clinical significance of positive serum auto-antibodies in
Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA
titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA
and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic
hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and
HCV genotype) were compared between patients with and without serum auto
antibodies. Fifty-eight (48%) patients were associated with positive serum auto
antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%)
positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters
(age, sex, blood transfusion history), liver biochemical tests, the presence of
cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not
significantly different between patients with and without positive serum auto
antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly
different between the two groups. Logistic regression analysis showed that none
of the previously mentioned parameters were significant predictors to associate
with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of
Chinese patients with chronic hepatitis C were associated with positive serum
auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not
correlated to the presence of serum auto-antibodies. The clinical significance
and actual pathogenesis of this phenomenon remain to be clarified.
PMID- 9641644
TI - Case report: Alanine aminotransferase deficiency detected in a patient with
chronic hepatitis C.
AB - We report a case of alanine aminotransferase (ALT) deficiency in a 68-year-old
Japanese female with chronic hepatitis C. The serum was positive for antibody to
hepatitis C virus (HCV) and HCV-RNA. Liver biopsy showed histological evidence of
chronic active hepatitis. The level of serum aspartate aminotransferase (sAST)
was elevated, but sALT was extremely low. The patient was followed up for her
serum aminotransferase levels for 1.5 years under the treatment with
ursodeoxycholic acid. The low sALT level persisted during all the follow-up
period. The ALT activity in liver tissue was also decreased. Based on these
findings, ALT deficiency was suspected. sALT activity was also found to be low in
her two sons. This latter finding suggests the hereditary character of this
abnormality.
PMID- 9641645
TI - Characterization of anti-histone antibodies in patients with type 1 autoimmune
hepatitis.
AB - We have recently found that antibodies to total histones are common in a group of
American patients with type 1 autoimmune hepatitis (AIH). In an attempt to
determine the profile and clinical association of anti-histone antibody (AHA), 45
Japanese AIH patients were studied for serum isotypic reactivity with individual
histones (H1, H2A, H2B, H3, H4) by enzyme-linked immunosorbent assay and western
blotting. The results revealed that 40% of sera had reactivities with at least
one of individual histones and that the antibodies were detected in all three
classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti-H3 showed
the dominant reactivity and it characterized 72% of sera with AHA. The titre of
anti-H3 decreased significantly (P < 0.0075) after steroid therapy and the index
of decrease for anti-H3 was correlated in individuals with that for serum
aminotransferase. In general, patients with AHA showed higher serum level of
alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher
frequency of A2-DR4 haplotype (53 vs 17%) than their seronegative counterparts.
However, the titre of AHA was low in this disease condition and histone class
specific antibodies did not distinguish patients with distinctive clinical
features, although patients with anti-H3 tended to be younger than those without
AHA.
PMID- 9641646
TI - Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune
hepatitis.
AB - Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients
with primary biliary cirrhosis, suggesting that UDCA has immunomodulating
effects. We investigated the effect of UDCA in patients with autoimmune hepatitis
(AIH) which is characterized by immunological abnormalities. Eight patients with
type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the
criteria of the International Autoimmune Hepatitis Group, five patients were
diagnosed as definite and three as probable type 1 AIH. Liver function tests were
performed every 4 weeks, before and during UDCA therapy and the serum levels of
anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G
and gamma globulin were determined every 3 months. The levels of serum aspartate
aminotransferase and alanine aminotransferase significantly decreased from 154 +/
24 IU/L and 170 +/- 17 IU/L before UDCA therapy to 31 +/- 3 IU/L and 25 +/- 5
IU/L (P < 0.001) after 1 year of treatment and 28 +/- 2 IU/L and 23 +/- 4 IU/L (P
< 0.001) after 2 years of treatment. After 2 years of treatment, the levels of
serum immunoglobulin G and gamma globulin significantly decreased (P < 0.05) and
ANA titres (5/8 patients) were reduced and SMA (3/5 patients) became negative.
Furthermore, hepatic histopathological changes of four patients were assessed
after 1 year of treatment, and an improvement of intrahepatic inflammation, but
not fibrosis, was observed. In conclusion, these results suggest that UDCA has a
beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.
PMID- 9641647
TI - Cystic fibrosis genotypes and alcoholic pancreatitis.
AB - Pancreatitis and pancreatic insufficiency are associated with both cystic
fibrosis and alcoholism. The pathogenesis of alcoholic pancreatitis is unknown,
but only a minority of alcoholics develop pancreatitis, and it has been suggested
that a genetic predisposition may play a role in this disease. Two observations
led to the hypothesis that this genetic predisposition could result from
mutations in the cystic fibrosis gene. First, the prevalence of cystic fibrosis
mutations in the Caucasian population (approximately 5%) is similar to the
prevalence of pancreatitis among heavy drinkers. Second, in both diseases,
pancreatic duct damage is a prominent feature and has been postulated to be the
initial site of injury. Therefore, the aim of this study was to determine whether
an increased frequency of mutations in the cystic fibrosis gene occurs in
alcoholic pancreatitis. The 15 most common cystic fibrosis mutations in a
Caucasian community were sought in 24 subjects with alcoholic pancreatitis. None
were homozygous or heterozygous for these mutations. These findings suggest that
cystic fibrosis mutations are not a major genetic factor predisposing to
pancreatic injury in alcoholics.
PMID- 9641648
TI - Helicobacter pylori colonization does not influence the symptomatic response to
prokinetic agents in patients with functional dyspepsia.
AB - Functional dyspepsia (FD) is very common, but the pathogenesis of Helicobacter
pylori leading to FD is still debated. The aim of this study was first to
evaluate the impact of H. pylori colonization on the efficacy of Paspertase (a
metoclopramide plus exogenous enzymes regimen for FD patients) and, second, to
compare the prevalence of H. pylori infection in FD patients with the general
population. Seventy-four consecutive FD patients were enrolled undergoing
Paspertase treatment. The symptomatic response was evaluated according to 1-4
scales of six main dyspeptic symptoms (i.e. epigastric pain/discomfort, early
satiety, heartburn, nausea/vomiting, abdominal fullness/bloating, and belching).
Nine hundred and seventy healthy subjects undergoing a paid physical check-up
were included to study the status of H. pylori colonization. The demographic data
and basal symptom scores between 43 H. pylori-positive and 31 H. pylori-negative
patients were not significantly different. Total and individual symptom scores
improved significantly after 4 weeks of Paspertase therapy (P < 0.05),
irrespective of H. pylori infection. The prevalences of H. pylori were very
similar in FD patients and the general population (58.1 vs 58.0%, NS). In
conclusion, these observations suggest that H. pylori colonization is not
significant in FD patients of Taiwan while a short-term prokinetic medication is
effective for these patients, irrespective of H. pylori status.
PMID- 9641649
TI - Prevalence of Helicobacter pylori in a representative Anglo-Celtic population of
urban Melbourne.
AB - The aims of this study were to assess the prevalence of Helicobacter pylori and
its relationship with different epidemiological factors in an Anglo-Celtic
Australian population in the Melbourne urban area. Two hundred and seventy-three
(120 men and 153 women with a mean age of 55.6 and range of 20 to 80 years) of
396 eligible subjects randomly sampled from the telephone directory were studied.
An ELISA technique was used to detect H. pylori immunoglobulin (Ig)G antibody and
self-administered questionnaires were completed. The overall seroprevalence of H.
pylori was 38% and increased with age from 18% (20-30 years old) to 53% (over 70
years; P < 0.0001). The acquisition of H. pylori infection was 1% per year. The
prevalence of H. pylori was 48% in men and 30% in women (P < 0.01). The frequency
of H. pylori was also associated with low-income levels and current smoking, but
was not associated with peptic ulcer disease history. The prevalence of H. pylori
infection in a representative Australian population was found to be similar to
other developed countries. The risk factors for H. pylori infection include age,
male sex, low household income and a smoking habit. No correlation between H.
pylori status and dyspepsia symptoms were observed.
PMID- 9641650
TI - Amount of Helicobacter pylori in gastric mucus during anti-H. pylori treatment.
AB - Helicobacter pylori is present in infected patients not only on the gastric
epithelial cell surface but also in gastric mucus. We developed a competitive
polymerase chain reaction (cPCR) method for quantitative measurement of H. pylori
in gastric mucus. The aim of this study was to determine the number of H. pylori
in gastric mucus before and after anti-H. pylori treatment. Patients with
duodenal ulcer were treated with lansoprazole alone (n = 11) or lansoprazole and
amoxycillin (n = 12). The amount of H. pylori in gastric mucus was measured over
time by a cPCR assay. Helicobacter pylori infection was also tested for using
histology, culture, and the rapid urease test (RUT). Although most patients
treated with lansoprazole alone had become H. pylori-negative by the end of
treatment when tested by histology, RUT, and culture, a large number of H. pylori
organisms were found in the gastric mucus at that time by cPCR. These patients
returned to being H. pylori positive 1 to 12 months later on the basis of
histology, RUT, and culture. However, cPCR results indicated eradication of H.
pylori by the end of treatment in eight of the 12 patients treated with
lansoprazole and amoxicillin, and these patients remained H. pylori negative on
histology, RUT, culture, and cPCR 1 to 12 months later. Testing for H. pylori in
gastric mucus is thus useful for precise determination of the success or failure
of H. pylori eradication therapy.
PMID- 9641651
TI - Enhanced levels of C-X-C chemokine, human GROalpha, in Helicobacter pylori
associated gastric disease.
AB - C-X-C Chemokines play an important role for neutrophil extravasation through
microvessels. Although the level of interleukin (IL)-8 is known to increase in
the Helicobacter pylori-infected gastric mucosa, another C-X-C chemokine,
GROalpha, has not been evaluated in the H. pylori-associated gastric mucosal
injury. The present study was designed to investigate gastric contents of
GROalpha in relation to those of IL-8 in the gastric mucosa of H. pylori-infected
peptic ulcer patients. Thirty-eight patients with gastric ulcer and 41 with
gastritis underwent endoscopy with informed consent and 49 were found to be H.
pylori positive and 30 H. pylori negative. Biopsies from the gastric corpus were
performed in each patient to examine the H. pylori colonization by bacterial
culture, the rapid urease test and histological specimens as well as measurement
of the contents of human GROalpha and IL-8. Helicobacter pylori infection was
eradicated in 21 patients by triple therapy (lansoprazole 30 mg, amoxycillin 2.0
g, clarithromycin 600 mg; 2 weeks). The samples for GROalpha and IL-8 assay were
homogenized in 0.02% aprotinin containing phosphate-buffered solution and the
mucosal contents of GROalpha and IL-8 in the supernatants were quantified by
sandwich enzyme immunoassay methods. The levels of GROalpha and IL-8 in H. pylori
positive gastric mucosa were significantly higher than those in the H. pylori
negative mucosa. There was a significant linear correlation between the levels of
GROalpha and IL-8 (r = 0.798, P < 0.01). After the eradication of H. pylori by
the triple therapy, the levels of GROalpha and IL-8 were significantly decreased.
The GROalpha showed an increase in the H. pylori-positive gastric mucosa in a
similar fashion as IL-8 contents, suggesting a pathogenetic role for GROalpha in
H. pylori-associated gastric mucosal injury.
PMID- 9641652
TI - Tamoxifen inhibits colorectal cancer metastases in the liver: a study in a murine
model.
AB - Liver metastases account for over 70% of deaths resulting from colorectal
carcinoma, with survival rates varying between 6-18 months. At present, surgical
resection offers the only hope for a cure, while chemotherapy, focal destructive
techniques and selective internal radiation offer palliative care. Tamoxifen, a
non-steroidal anti-oestrogen is primarily known for treating oestrogen receptor
(ER)-positive breast cancer. Some studies suggest that tamoxifen may have
beneficial effects in malignancies other than breast cancer. These inhibitory
effects, which have been shown to be independent of the ER, highlight new
mechanisms of therapeutic action. Using an intrasplenic animal model we report
the efficacy of tamoxifen on experimental liver metastases. In this model, a
dimethyl hydrazine-induced colon carcinoma cell suspension is introduced into the
portal circulation via the spleen, which results in secondary tumour deposits in
the liver in virtually all animals. Tamoxifen was administered at a dose of 1
mg/kg suspended in 1.0% methyl cellulose. The control group received an equal
volume of the vehicle. The reagents were administered s.c. on the day of
metastases induction and were continued daily over a 4 week period. The effect of
tamoxifen on tumour growth was assessed by stereology and bromodeoxyuridine
immunohistochemistry at selected time points. Data were assessed by a multiple
analysis of variance where P < 0.05 was considered significant. In the control
group the volume of metastases increased from 44 +/- 41 mm3 at day 10 to 517 +/-
380 mm3, 1394 +/- 598 mm3 and 2082 +/- 675 mm3 by days 16, 22 and 28,
respectively. Daily administration of tamoxifen exerted an inhibitory effect on
tumour growth during the first 3 weeks, recording a volume of 421 +/- 299 mm3 by
day 22 compared with the control group at that time point (P = 0.00004). The
inhibitory effect diminished by the fourth week recording a tumour volume of 1344
+/- 674 mm3 by day 28. Inhibition of tumour growth at day 22 coincides with a
reduction of cells in the S phase of the cell cycle. The percentage of brdU
positive nuclear profiles in metastases of tamoxifen-treated mice at 3 weeks was
35.87 +/- 5.60% compared with 48.01 +/- 3.96% in the control group (P = 0.001).
These data suggest that tamoxifen has a potent inhibitory action on colorectal
liver metastases by exerting an effect on cell proliferation.
PMID- 9641653
TI - What's new in colorectal cancer screening?
AB - There is now good evidence from case control studies and randomized controlled
trials that screening average-risk subjects for colorectal cancer using faecal
occult blood tests reduces mortality. There is limited data indicating that
screening sigmoidoscopy can also achieve this. There is no evidence yet that
screening by colonoscopy or double contrast barium enema can reduce mortality.
Calculations of cost-effectiveness suggest that all of the above strategies
should be economically worthwhile but there is no convincing evidence to suggest
that one strategy is markedly more cost-effective than the others. Further data
on several aspects of screening are required before any decisions are made on
which form(s) of screening should be offered nationwide.
PMID- 9641654
TI - Case report: Pneumatosis cystoides intestinalis associated with post-surgical
bowel anastomosis: a report of three cases and review of the Japanese literature.
AB - We report three cases of pneumatosis cystoides intestinalis (PCI) occurring in
association with post-surgical bowel anastomosis. A 74-year-old man, a 58-year
old woman, and a 62-year-old woman were found to have PCI at the colonic side of
a bowel anastomosis at 4 years, 3 years and 1 year after operation, respectively,
for right colon carcinoma, although all were asymptomatic. They all had a
positive anti-nuclear antibody test and had received postoperative cancer
chemotherapy. The clinical features of 123 cases of PCI reported in Japan between
1981 and 1995 were also reviewed. On the basis of the present and previous cases,
we propose that post-surgical anastomosis, cancer chemotherapy, and
predisposition to collagen vascular disease might be responsible for the damage
to intestinal mucosa that leads to the development of PCI.
PMID- 9641655
TI - Images in gastroenterology. Occult rectal prolapse and solitary rectal ulcer.
PMID- 9641656
TI - Hepatobiliary and pancreatic imaging. Retroperitoneal mature cystic teratoma with
a fat ball.
PMID- 9641657
TI - Chronic hepatitis virus infection in children.
AB - Hepatitis B and C viruses (HBV and HCV) are the two main hepatitis viruses
causing chronic liver diseases in children. In hyperendemic areas, nearly half of
the primary infection in chronic HBV carriers occurs during the perinatal period
through the transmission from hepatitis B e antigen (HBeAg)-positive mothers. The
other half are from horizontal transmission mainly through intrafamilial spread
or injection using unsterilized needles. During the natural course of chronic HBV
infection, spontaneous HBeAg/anti-HBe seroconversion occurs very rarely (2%
annually) before 3 years of age. After 3 years of age, the HBeAg seroconversion
rate increases gradually to 5% per year. Those with mothers who are hepatitis B
carriers tend to clear HBeAg slower than those whose mothers are non-carriers.
Transplacental HBeAg may cause T cell tolerance in infected children. Universal
HBV immunization programmes have been effective in reducing the hepatitis B
carrier rate more than 10-fold, and the incidence of hepatocellular carcinoma in
children has also been decreased significantly. Hepatitis C virus infection
occurs mainly in high-risk children, such as those who received blood products
(blood diseases, malignancies, post-open heart surgery etc.), children of HCV
infected mothers, and in hyperendemic areas, from injection using unsterile
needles. Mother-to-infant transmission occurs on average in 5% of infants of
viraemic mothers. The maternal HCV-RNA titre is the most important factor
determining the infectivity. Chronicity developed in 60-80% of HCV-infected
children. Although transient or persistent elevation of aminotransferases occurs
frequently in chronically HCV-infected children, liver histology showed minimal
or mild changes only. The most prevalent genotype of HCV in children is Ib.
Screening of the blood products for HCV antibody has markedly reduced the rate of
HCV infection in children at risk. However, vaccine development is needed to
prevent mother-to-infant transmission and other routes of infections.
PMID- 9641658
TI - Benefits of federation.
PMID- 9641659
TI - Call to drop charges in French blood affair.
PMID- 9641660
TI - US research safety system 'in jeopardy'.
PMID- 9641661
TI - Job discrimination based on genetics set for California ban.
PMID- 9641662
TI - Japanese media fuel fears of 'endocrine disrupters'.
PMID- 9641663
TI - Canada putting its faith in consolidation in health sector.
PMID- 9641664
TI - Europeans adapt to compete with US neuroscience body.
PMID- 9641665
TI - Cell biologists set out on the path of reform.
PMID- 9641666
TI - Avenues of discovery in bioprospecting.
PMID- 9641667
TI - Avenues of discovery in bioprospecting.
PMID- 9641668
TI - Cancer controversy.
PMID- 9641669
TI - No conference critique.
PMID- 9641670
TI - Congressional hearings on genetics research.
PMID- 9641671
TI - Circadian rhythms. New cogwheels in the clockworks.
PMID- 9641672
TI - Molecular motors. Keeping the beat.
PMID- 9641673
TI - HIV. Envelope's letters boxed into shape.
PMID- 9641674
TI - Pere Alberch (1954-98)
PMID- 9641675
TI - Mechanisms for memory types differ.
PMID- 9641676
TI - Walking on Mars.
PMID- 9641677
TI - Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor
and a neutralizing human antibody.
AB - The entry of human immunodeficiency virus (HIV) into cells requires the
sequential interaction of the viral exterior envelope glycoprotein, gp120, with
the CD4 glycoprotein and a chemokine receptor on the cell surface. These
interactions initiate a fusion of the viral and cellular membranes. Although
gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We
have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120
core complexed with a two-domain fragment of human CD4 and an antigen-binding
fragment of a neutralizing antibody that blocks chemokine-receptor binding. The
structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site
for the chemokine receptor, evidence for a conformational change upon CD4
binding, the nature of a CD4-induced antibody epitope, and specific mechanisms
for immune evasion. Our results provide a framework for understanding the complex
biology of HIV entry into cells and should guide efforts to intervene.
PMID- 9641678
TI - A nutrient-sensing pathway regulates leptin gene expression in muscle and fat.
AB - Leptin, the protein encoded by the obese (ob) gene, is synthesized and released
in response to increased energy storage in adipose tissue. However, it is still
not known how incoming energy is sensed and transduced into increased expression
of the ob gene. The hexosamine biosynthetic pathway is a cellular 'sensor' of
energy availability and mediates the effects of glucose on the expression of
several gene products. Here we provide evidence for rapid activation of ob gene
expression in skeletal muscle by glucosamine. Increased tissue concentrations of
the end product of the hexosamine biosynthetic pathway, UDP-N-acetylglucosamine
(UDP-GlcNAc), result in rapid and marked increases in leptin messenger RNA and
protein levels (although these levels were much lower than those in fat). Plasma
leptin levels and leptin mRNA and protein levels in adipose tissue also increase.
Most important, stimulation of leptin synthesis is reproduced by either
hyperglycaemia or hyperlipidaemia, which also increase tissue levels of UDP-N
acetylglucosamine in conscious rodents. Finally, incubation of 3T3-L1 pre
adipocytes and L6 myocytes with glucosamine rapidly induces ob gene expression.
Our findings are the first evidence of inducible leptin expression in skeletal
muscle and unveil an important biochemical link between increased availability of
nutrients and leptin expression.
PMID- 9641679
TI - Male-to-female sex reversal in M33 mutant mice.
AB - Polycomb genes in Drosophila maintain the repressed state of homeotic and other
developmentally regulated genes by mediating changes in higher-order chromatin
structure. M33, a mouse homologue of Polycomb, was isolated by means of the
structural similarity of its chromodomain. The fifth exon of M33 contains a
region of homology shared by Drosophila and Xenopus. In Drosophila, its deletion
results in the loss of Polycomb function. Here we have disrupted M33 in mice by
inserting a poly(A) capture-type neo(r) targeting vector into its fifth exon.
More than half of the resultant M33cterm/M33cterm mutant mice died before
weaning, and survivors showed male-to-female sex reversal. Formation of genital
ridges was retarded in both XX and XY M33cterm/M33cterm embryos. Gonadal growth
defects appeared near the time of expression of the Y-chromosome-specific Sry
gene, suggesting that M33 deficiency may cause sex reversal by interfering with
steps upstream of Sry. M33cterm/M33cterm mice may be a valuable model in which to
test opposing views regarding sex determination.
PMID- 9641680
TI - Premotor commands encode monocular eye movements.
AB - Binocular coordination of eye movements is essential for stereopsis (depth
perception) and to prevent double vision. More than a century ago, Hering and
Helmholtz debated the neural basis of binocular coordination. Helmholtz believed
that each eye is controlled independently and that binocular coordination is
learned. Hering believed that both eyes are innervated by common command signals
that yoke the eye movements (Hering's law of equal innervation). Here we provide
evidence that Hering's law is unlikely to be correct. We show that premotor
neurons in the paramedian pontine reticular formation that were thought to encode
conjugate velocity commands for saccades (rapid eye movements) actually encode
monocular commands for either right or left eye saccades. However, 66% of the
abducens motor neurons, which innervate the ipsilateral lateral rectus muscle,
fire as a result of movements of either eye. The distribution of sensitivity to
ipsilateral and contralateral eye movements across the abducens motor neuron pool
may provide a basis for learning binocular coordination in infancy and adapting
it throughout life.
PMID- 9641681
TI - Silent glutamatergic synapses and nociception in mammalian spinal cord.
AB - Neurons in the superficial dorsal horn of the spinal cord are important for
conveying sensory information from the periphery to the central nervous system.
Some synapses between primary afferent fibres and spinal dorsal horn neurons may
be inefficient or silent. Ineffective sensory transmission could result from a
small postsynaptic current that fails to depolarize the cell to threshold for an
action potential or from a cell with a normal postsynaptic current but an
increased threshold for action potentials. Here we show that some cells in the
superficial dorsal horn of the lumbar spinal cord have silent synapses: they do
not respond unless the holding potential is moved from -70 mV to +40 mV.
Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter of the raphe
spinal projecting pathway, transforms silent glutamatergic synapses into
functional ones. Therefore, transformation of silent glutamatergic synapses may
serve as a cellular mechanism for central plasticity in the spinal cord.
PMID- 9641682
TI - Synaptic laminin prevents glial entry into the synaptic cleft.
AB - Presynaptic and postsynaptic membranes directly oppose each other at chemical
synapses, minimizing the delay in transmitting information across the synaptic
cleft. Extrasynaptic neuronal surfaces, in contrast, are almost entirely covered
by processes from glial cells. The exclusion of glial cells from the synaptic
cleft, and the long-term stability of synapses, presumably result in large part
from the tight adhesion between presynaptic and postsynaptic elements. Here we
show that there is another requirement for synaptic maintenance: glial cells of
the skeletal neuromuscular synapse, Schwann cells, are actively inhibited from
entering the synaptic cleft between the motor nerve terminal and the muscle
fibre. One inhibitory component is laminin 11, a heterotrimeric glycoprotein that
is concentrated in the synaptic cleft. Regulation of an inhibitory interaction
between glial cells and synaptic cleft components may contribute to synaptic
rearrangements, and loss of this inhibition may underlie the loss of synapses
that results from injury to the postsynaptic cell.
PMID- 9641683
TI - Association of missense and 5'-splice-site mutations in tau with the inherited
dementia FTDP-17.
AB - Thirteen families have been described with an autosomal dominantly inherited
dementia named frontotemporal dementia and parkinsonism linked to chromosome 17
(FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal
and/or glial inclusions that stain positively with antibodies raised against the
microtubule-associated protein Tau, although the Tau pathology varies
considerably in both its quantity (or severity) and characteristics. Previous
studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome
17q21.11; the tau gene also lies within this region. We have now sequenced tau in
FTDP-17 families and identified three missense mutations (G272V, P301L and R406W)
and three mutations in the 5' splice site of exon 10. The splice-site mutations
all destabilize a potential stem-loop structure which is probably involved in
regulating the alternative splicing of exon10. This causes more frequent usage of
the 5' splice site and an increased proportion of tau transcripts that include
exon 10. The increase in exon 10+ messenger RNA will increase the proportion of
Tau containing four microtubule-binding repeats, which is consistent with the
neuropathology described in several families with FTDP-17.
PMID- 9641684
TI - The antigenic structure of the HIV gp120 envelope glycoprotein.
AB - The human immunodeficiency virus HIV-1 establishes persistent infections in
humans which lead to acquired immunodeficiency syndrome (AIDS). The HIV-1
envelope glycoproteins, gp120 and gp41, are assembled into a trimeric complex
that mediates virus entry into target cells. HIV-1 entry depends on the
sequential interaction of the gp120 exterior envelope glycoprotein with the
receptors on the cell, CD4 and members of the chemokine receptor family. The
gp120 glycoprotein, which can be shed from the envelope complex, elicits both
virus-neutralizing and non-neutralizing antibodies during natural infection.
Antibodies that lack neutralizing activity are often directed against the gp120
regions that are occluded on the assembled trimer and which are exposed only upon
shedding. Neutralizing antibodies, by contrast, must access the functional
envelope glycoprotein complex and typically recognize conserved or variable
epitopes near the receptor-binding regions. Here we describe the spatial
organization of conserved neutralization epitopes on gp120, using epitope maps in
conjunction with the X-ray crystal structure of a ternary complex that includes a
gp120 core, CD4 and a neutralizing antibody. A large fraction of the predicted
accessible surface of gp120 in the trimer is composed of variable, heavily
glycosylated core and loop structures that surround the receptor-binding regions.
Understanding the structural basis for the ability of HIV-1 to evade the humoral
immune response should assist in the design of a vaccine.
PMID- 9641685
TI - Dynein arms are oscillating force generators.
AB - Eukaryotic flagella beat rhythmically. Dynein is a protein that powers flagellar
motion, and oscillation may be inherent to this protein. Here we determine
whether oscillation is a property of dynein arms themselves or whether
oscillation requires an intact axoneme, which is the central core of the
flagellum and consists of a regular array of microtubules. Using optical trapping
nanometry, we measured the force generated by a few dynein arms on an isolated
doublet microtubule. When the dynein arms on the doublet microtubule contact a
singlet microtubule and are activated by photolysis of caged ATP8, they generate
a peak force of approximately 6pN and move the singlet microtubule over the
doublet microtubule in a processive manner. The force and displacement oscillate
with a peak-to-peak force and amplitude of approximately 2 pN and approximately
30 nm, respectively. The geometry of the interaction indicates that very few
(possibly one) dynein arms are needed to generate the oscillation. The maximum
frequency of the oscillation at 0.75 mM ATP is approximately 70 Hz; this
frequency decreases as the ATP concentration decreases. A similar oscillatory
force is also generated by inner dynein arms alone on doublet microtubules that
are depleted of outer dynein arms. The oscillation of the dynein arm may be a
basic mechanism underlying flagellar beating.
PMID- 9641686
TI - Meeting highlights: 47th Annual Scientific Sessions of the American College of
Cardiology.
PMID- 9641687
TI - Reactive oxygen species, metalloproteinases, and plaque stability.
PMID- 9641688
TI - Coronary bypass grafting with bilateral internal thoracic arteries and the right
gastroepiploic artery.
PMID- 9641689
TI - International, randomized, controlled trial of lamifiban (a platelet glycoprotein
IIb/IIIa inhibitor), heparin, or both in unstable angina. The PARAGON
Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary
syndrome events in a Global Organization Network.
AB - BACKGROUND: Unstable angina and non-Q-wave myocardial infarction involve coronary
arterial plaque rupture, platelet activation, and thrombus formation. This study
tested the benefit of different doses of lamifiban (a platelet IIb/IIIa
antagonist) alone and in combination with heparin in patients with these
conditions to select the most promising lamifiban regimen for subsequent
evaluation. METHODS AND RESULTS: At 273 hospitals in 20 countries, 2282 patients
were randomly assigned to lamifiban (2x2 factorial design: low-dose [1
microg/min] with and without heparin versus high-dose [5 microg/min] with and
without heparin) or to standard therapy (placebo and heparin). All patients
received aspirin. The composite primary end point of death or nonfatal myocardial
infarction at 30 days occurred in 11.7% of those receiving standard therapy,
10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lamifiban
(P=0.668). By 6 months, this composite was lowest for those assigned to low-dose
lamifiban (P=0.027) and intermediate for those assigned to high-dose lamifiban
(P=0.450) compared with control (13.7%, 16.4%, and 17.9%, respectively). Compared
with control, the combination of high-dose lamifiban and heparin resulted in more
intermediate or major bleeding (12.1% versus 5.5%; P=0.002) and a similar rate of
ischemic events. Conversely, low-dose lamifiban and heparin yielded similar
bleeding rates as in the control group but fewer ischemic events at 6 months
(12.6% versus 17.9%; P=0.025). CONCLUSION: In unstable angina and non-Q-wave
infarction, platelet IIb/IIIa antagonism with lamifiban reduces adverse ischemic
events at 6 months beyond that of aspirin and heparin therapy. The role of
conjunctive heparin remains uncertain but appears more favorable with low-dose
IIb/IIIa antagonism. Larger-scale study is needed to more reliably estimate these
effects.
PMID- 9641690
TI - Interlesion dependence of the risk for restenosis in patients with coronary stent
placement in in multiple lesions.
AB - BACKGROUND: Little is known about the behavior with regard to restenosis of
multiple lesions within the same patient treated with intracoronary stenting. Our
objective was to test the hypothesis that there is an intrapatient dependence of
restenosis between lesions. METHODS AND RESULTS: Quantitative analysis was
carried out on angiograms obtained before, immediately after, and at 6 months
after coronary stent placement in 1734 lesions in 1244 patients. We used a
specialized logistic regression that not only accounts for intraclass correlation
but also quantifies it in the form of odds ratio (OR) as the change in risk of a
lesion to develop restenosis if another companion lesion had restenosis. The
model was based on 23 patient- and lesion-related variables with binary
restenosis (diameter stenosis > or =50%) as end point. The overall restenosis
rate was 27.5%: 24.4% for single-lesion, 28.6% for double-lesion, and 33.8% for >
or =3-lesion interventions. After adjustment for the influence of significant
factors (hypercholesterolemia, systemic arterial hypertension, diabetes mellitus,
previous PTCA, ostial lesion, location in left anterior descending coronary
artery, number of stents placed, vessel size, stenosis severity, balloon-to
vessel ratio, and final result), the analysis found a significant intrapatient
correlation, OR 2.5 (1.8 to 3.6). This means that in patients with multilesion
interventions, the risk of a lesion to develop restenosis is 2.5 times higher if
a companion lesion has restenosis, independently of the presence or absence of
analyzed patient risk factors (eg, diabetes). CONCLUSIONS: This study
demonstrates that there is a dependence of restenosis between coronary lesions in
patients who undergo a multilesion intervention. The likelihood of restenosis for
a lesion is higher when another companion lesion has also developed restenosis.
Other, as yet unidentified patient factors may be the source of this intrapatient
correlation of restenosis.
PMID- 9641691
TI - Low recurrence of angina pectoris after coronary artery bypass graft surgery with
bilateral internal thoracic and right gastroepiploic arteries.
AB - BACKGROUND: In the past 10 years, there has been a trend to use more arterial
grafts instead of vein grafts for coronary artery bypass graft surgery. Although
there are many reports on the short- and mid-term follow-up of patients who
underwent arterial revascularization with 1 or 2 arteries, little has been
reported on the follow-up of patients with 3-vessel disease who received 3
arteries. METHODS AND RESULTS: We reviewed a group of 256 patients with 3-vessel
disease who received the right gastroepiploic artery together with both internal
thoracic arteries (ITAs). Vein grafts were not used in these patients. The
patients were monitored for up to 7 years (mean, 51+/-15 months). Seven-year
actuarial survival was 91.1%. The cumulative probability of event-free survival
for myocardial infarction, reintervention, and angina pectoris at 7 years was
97.3%, 95.4%, and 85.4%, respectively. CONCLUSIONS: We conclude that concomitant
use of the gastroepiploic artery with both ITAs results in low mortality and a
low incidence of myocardial infarction and reintervention at follow-up. Most
interestingly, we found 85.4% freedom from angina pectoris after 7 years, which
is considerably lower than the results of studies in which vein grafts, single
ITA grafts, or double ITA grafts are used. These results strongly support the use
of both ITAs and the right gastroepiploic artery for bypass grafting in patients
with 3-vessel disease.
PMID- 9641693
TI - Sympathetic denervation and reinnervation after arterial switch operation for
complete transposition.
AB - BACKGROUND: Sympathetic cardiopulmonary nerves arise from the cervical
sympathetic trunks and the stellate ganglia and subsequently course along the
origin of the great arteries and the coronary arteries to innervate the
ventricles. Therefore, the sympathetic nerves may be obligatorily interrupted by
the arterial switch operation (ASO) for complete transposition of the great
arteries. METHODS AND RESULTS: To demonstrate and characterize the possible
sympathetic denervation, 51 patients after ASO, 4.8 years old (range, 1 month to
10.1 years), underwent [123I]metaiodobenzylguanidine (MIBG) imaging of the
sympathetic nerve terminal. MIBG uptake to the heart was graded by quantitative
analysis using the heart-to-mediastinum (H/M) ratio of MIBG uptake. A
quantitative criterion for absent uptake of MIBG was set to 1.48 in the H/M
ratio. Four patients < 1 month after ASO showed complete absence of MIBG uptake,
which had been observed preoperatively. In contrast, 47 patients late after ASO
(range, 15 months to 10.1 years) showed various degrees of uptake of MIBG.
Patients operated on at < or =55 days of age showed positive MIBG uptake much
more frequently than those operated on at later ages. Heart rate and rate
pressure product at peak exercise on a treadmill exercise test were significantly
greater in patients with positive uptake than in those with absent uptake of
MIBG. CONCLUSIONS: Cardiac sympathetic nerves were denervated early after and
reinnervated late after ASO. Neonatal ASO may be favorable to facilitate
sympathetic reinnervation, which may affect exercise tolerance late after
surgery.
PMID- 9641692
TI - Differential leukotriene constrictor responses in human atherosclerotic coronary
arteries.
AB - BACKGROUND: Leukotrienes are a class of biologically active lipids that have
potent effects on the heart. To assess their role in coronary artery disease, we
compared the contractile responses of leukotriene C4 (LTC4) and leukotriene D4
(LTD4) and their binding activity in both atherosclerotic and nonatherosclerotic
human coronary arteries. We also studied expression of the enzymes that control
their formation to understand how the 5-lipoxygenase (5-LO) pathway is activated
in the coronary arteries. METHODS AND RESULTS: The capacity of leukotrienes to
affect coronary vessel tone and the influence of atherosclerosis was tested in
organ baths. Leukotriene receptors were examined by autoradiography, and antibody
binding to the various enzymes responsible for their formation was assessed by
use of immunocytochemistry. Nonatherosclerotic coronary artery ring segments were
unresponsive to LTC4 and LTD4. In contrast, LTC4 and LTD4 induced concentration
dependent contractions in atherosclerotic coronary arteries. Specific [3H]-LTC4
but not LTD4 binding to atherosclerotic coronary artery was evident, with no
evidence of specific binding of [3H]-leukotrienes to nonatherosclerotic coronary
artery. High-resolution autoradiography identified specific [3H]-LTC4 binding
sites to smooth muscle cell and to regions of intimal proliferation and plaque.
Cells showing positive antibody binding to 5-LO, FLAP (5-lipoxygenase activating
protein), and leukotriene A4 hydrolase were also present in the coronary arteries
and had a similar distribution to macrophages. CONCLUSIONS: Atherosclerosis is
associated with a specific leukotriene receptor(s) capable of inducing
hyperreactivity of human epicardial coronary arteries in response to LTC4 and
LTD4.
PMID- 9641694
TI - A recessive variant of the Romano-Ward long-QT syndrome?
AB - BACKGROUND: The congenital long-QT syndrome (LQTS) is a genetically heterogeneous
disease characterized by prolonged ventricular repolarization and life
threatening arrhythmias. Mutations of the KVLQT1 gene, a cardiac potassium
channel, generate two allelic diseases: the Romano-Ward syndrome, inherited as a
dominant trait, and the Jervell and Lange-Nielsen syndrome, inherited as an
autosomal recessive trait. METHODS AND RESULTS: A consanguineous family with the
clinical phenotype of LQTS was screened for mutations in the KVLQT1 gene.
Complementary RNAs for injection into Xenopus oocytes were prepared, and currents
were recorded with the double microelectrode technique. A homozygous missense
mutation, leading to an alanine-to-threonine substitution at the beginning of the
pore domain of the KVLQT1 channel, was found in the proband, a 9-year-old boy
with normal hearing, a prolonged QT interval, and syncopal episodes during
physical exercise. The parents of the proband were heterozygous for the mutation
and had a normal QT interval. The functional evaluation of the mutant channel
activity showed reduction in total current, a hyperpolarizing shift in
activation, and a faster activation rate consistent with a mild mutation likely
to require homozygosity to manifest the phenotype. CONCLUSIONS: These findings
provide the first evidence for a recessive form of the Romano-Ward long-QT
syndrome and indicate that homozygous mutations on KVLQT1 do not invariably
produce the Jervell and Lange-Nielsen syndrome. The implications of this
observation prompt a reconsideration of the penetrance of different mutations
responsible for LQTS and suggest that mild mutations in LQTS genes may be present
among the general population and may predispose to drug-induced ventricular
arrhythmias.
PMID- 9641695
TI - New method for nonfluoroscopic endocardial mapping in humans: accuracy assessment
and first clinical results.
AB - BACKGROUND: Accurate mapping of the site of origin and activation sequence of a
cardiac arrhythmia is essential for a successful catheter ablation procedure. To
achieve this, precise and reproducible catheter manipulation is mandatory. The
aim of this study was (1) to assess the accuracy of a new nonfluoroscopic mapping
system in humans and (2) to report the first result of endocardial activation
mapping with this system during sinus rhythm and several types of
supraventricular and ventricular tachycardias. METHODS AND RESULTS: Fifteen
patients were studied. Accuracy measurements were performed in 5 of them
(patients 5, 6, 7, 8, and 14). The distances between two subsequent catheter
positions in the inferior caval vein as determined by the nonfluoroscopic mapping
system were compared with measurements made with calipers by four independent
investigators using identification marks on the catheter shaft. The difference
between these two methods was 0.95+/-0.8 mm. In 15 patients, activation of the
right atrium and/or the right or left ventricle was recorded during sinus rhythm.
Three-dimensional activation maps were constructed in patients with atrial and
ventricular tachycardias and Wolff-Parkinson-White syndrome. CONCLUSIONS: With
this new nonfluoroscopic mapping technique, accurate positioning of the catheter
tip is possible. A three-dimensional activation map can be reconstructed during
sinus rhythm and during supraventricular and ventricular tachycardias of
different compartments of the heart.
PMID- 9641696
TI - Lipid lowering by diet reduces matrix metalloproteinase activity and increases
collagen content of rabbit atheroma: a potential mechanism of lesion
stabilization.
AB - BACKGROUND: Proteolytic enzyme activity in lipid-rich atheroma may promote plaque
rupture and precipitate acute coronary syndromes. This study tested the
hypothesis that lipid lowering stabilizes plaques by reducing proteolytic
activity. METHODS AND RESULTS: We produced experimental atheroma in 33 rabbits by
balloon injury and an atherogenic diet (0.3% cholesterol and 4.7% coconut oil)
for 4 months. At that time, 15 rabbits were killed (baseline group). The
remaining animals were divided into two groups: a hyperlipemic group continued to
consume a cholesterol-enriched diet (0.05% to 0.2%) for 16 more months (n=5) and
a lipid-lowering group consumed a purified chow diet with no added cholesterol or
fat for 8 (n=3) or 16 months (n=10). Macrophage accumulation and interstitial
collagenase (matrix metalloproteinase-1, MMP-1) expression in the lesion were
measured by quantitative image analysis of standardized sections of immunostained
aortas. Baseline lesions expressed high levels of MMP-1 and contained many
macrophages. These features of plaque instability persisted in the hyperlipemic
group. However, the lipid-lowering group showed progressive reduction in both
macrophage content and MMP- 1 immunoreactivity with time. Aortic rings of the
baseline and hyperlipemic groups elaborated gelatinolytic, caseinolytic, and
elastinolytic activity attributable to MMP-2, MMP-3, or MMP-9, monitored by SDS
PAGE zymography. Proteolytic activity decreased markedly in the lipid-lowering
group. Aortic content of interstitial collagen, determined by sirius red
staining, increased in the lipid-lowering group compared with the baseline or
continued hyperlipemic groups, indicating that lipid lowering reinforced the
fibrous skeleton of the atheroma. CONCLUSIONS: These results establish a
mechanism by which lipid lowering may stabilize vulnerable plaques by reduced
expression and activity of enzymes that degrade the arterial extracellular matrix
and render atheroma less susceptible to disruption and thrombosis by favoring
collagen accumulation in the fibrous cap.
PMID- 9641697
TI - N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived
foam cells: new target for antioxidant therapy?
AB - BACKGROUND: Atherosclerotic plaque destabilization triggers clinical
cardiovascular disease and thus represents an attractive therapeutic target.
Weakening of tissue through the action of matrix-degrading enzymes, called matrix
metalloproteinases (MMPs), released by resident macrophages was previously
implicated in unstable vascular syndromes. METHODS AND RESULTS: We used a
hypercholesterolemic rabbit model of atherosclerosis to investigate the
gelatinolytic activity associated with macrophage-derived foam cells (FCs).
Gelatinolytic activity and expression of MMP-9 but not of MMP-2 cosegregated with
macrophage FCs in aortic lesions. Macrophage-derived gelatinases were further
investigated in vitro. MMP-9 was identified as the main macrophage-derived
gelatinase in cells isolated from aortic lesions and from granuloma induced in
the same rabbits to increase cell yield. Importantly, detection of activated MMP
9 in the FC culture medium supports the notion that these cells can independently
initiate processing of secreted MMP zymogens to active enzymes. We further
examined whether FC gelatinolytic activity is dependent on the presence of
reactive oxygen species (ROS). We found that treatment (1 to 5 days) with 1 to 10
mmol/L N-acetyl-L-cysteine (NAC), an ROS scavenger, decreased not only
gelatinolytic activity but also gelatinase expression by FCs. Similarly, NAC
treatment of explanted lesions abolished in situ gelatinolytic activity and MMP-9
expression. CONCLUSIONS: Macrophage FCs are an abundant source of gelatinolytic
activity that can be inhibited in vitro and in situ by NAC. This newly described
action of antioxidant therapy might prove useful to inhibit matrix degradation
and to improve vascular stability.
PMID- 9641698
TI - Profound underestimation of glucose uptake by [18F]2-deoxy-2-fluoroglucose in
reperfused rat heart muscle.
AB - BACKGROUND: [18F]2-deoxy-2-fluoroglucose (FDG) is widely used as a tracer for
glucose uptake in ischemic heart muscle. We tested the effects of low-flow
ischemia and reperfusion on the ratio of tracer/tracee (lumped constant, LC).
METHODS AND RESULTS: Isolated working rat hearts were perfused with Krebs
Henseleit buffer containing only glucose 5 mmol/L (group 1) or glucose 5 mmol/L
plus oleate 0.4 mmol/L (group 2, fed; group 3, fasted). Dynamic glucose uptake
was measured simultaneously with [2-3H]glucose and with FDG. After 20 minutes,
coronary flow was reduced by 75% for 30 minutes before it was returned to control
conditions for the final 20 minutes. Hexokinase activity in the cytosolic and
mitochondrial fractions and tissue metabolites were determined. Rates of glucose
uptake were highest when glucose was the only substrate. Glucose uptake, FDG
uptake, and the LC increased during ischemia only in group 3. There was no change
of these parameters during ischemia in groups 1 and 2. FDG uptake decreased
significantly with reperfusion in groups 2 and 3, and there was a striking fall
in the LC (from >1.0 to <0.2, P<.001). The fall in the LC was associated with a
significant increase in intracellular free glucose. Neither ischemia nor
reperfusion affected the kinetic properties of hexokinase. CONCLUSIONS: FDG
profoundly underestimates glucose uptake during reperfusion in the presence of
fatty acids. In the fasted state, however, FDG overestimates glucose uptake
during ischemia. The results indicate limitations in the use of FDG to quantify
myocardial glucose uptake in human heart.
PMID- 9641699
TI - Mitochondrial ATP-dependent potassium channels: novel effectors of
cardioprotection?
AB - BACKGROUND: Brief interruptions of coronary blood flow paradoxically protect the
heart from subsequent prolonged ischemia. The basis of such endogenous
cardioprotection, known as "ischemic preconditioning," remains uncertain.
Pharmacological evidence has implicated ATP-dependent potassium (KATP) channels
in the mechanism of preconditioning; however, the effects of sarcolemmal KATP
channels on excitability cannot account for the protection. METHODS AND RESULTS:
We simultaneously measured flavoprotein fluorescence, an index of mitochondrial
redox state, and sarcolemmal KATP currents in intact rabbit ventricular myocytes.
Our results show that diazoxide, a KATP channel opener, selectively activates
mitochondrial KATP channels. Diazoxide induced reversible oxidation of
flavoproteins with an EC50 of 27 micromol/L but did not activate sarcolemmal KATP
channels. The subcellular site of diazoxide action is further localized to
mitochondria by confocal imaging of fluorescence arising from flavoproteins and
tetramethylrhodamine ethyl ester. In a cellular model of simulated ischemia,
inclusion of diazoxide decreased the rate of cell death to about half of that in
controls. Both the redox changes and protection are inhibited by the KATP channel
blocker 5-hydroxydecanoic acid. CONCLUSIONS: Our results demonstrate that
diazoxide targets mitochondrial but not sarcolemmal KATP channels and imply that
mitochondrial KATP channels may mediate the protection from KATP channel openers.
PMID- 9641700
TI - Images in cardiovascular medicine. Intramyocardial dissecting hematoma.
PMID- 9641701
TI - Images in cardiovascular medicine. Infected dual-chamber pacemaker leads.
PMID- 9641702
TI - The American Heart Association Stroke Outcome Classification: executive summary.
PMID- 9641703
TI - Youth violence: If we are not active in prevention efforts, who will be?
PMID- 9641704
TI - Violence exposure and emotional trauma as contributors to adolescents' violent
behaviors.
AB - OBJECTIVE: To investigate the degree to which violence exposure and symptoms of
psychological trauma are related to adolescents' own violent behaviors. DESIGN
AND SETTING: Anonymous self-report questionnaire administered to students in 6
public high schools (grades 9-12). PARTICIPANTS: Sixty-eight percent of the
students attending the participating schools during the survey participated in
the study (N=3735). Ages ranged from 14 to 19 years; 52% were female; and 35%
were African American, 33% white, and 23% Hispanic. RESULTS: Multiple regression
analysis determined that violence exposure and symptoms of psychological trauma
together explained more than 50% of the variance in both male and female self
reported violent behavior. The independent effects of exposure to violence
explained about one quarter of the variance in both male and female adolescents'
violent behaviors. Anger was found to be the leading trauma symptom. CONCLUSION:
Our findings suggest that health clinicians and other professionals who encounter
adolescents should routinely screen them for both exposure to violence and
symptoms of anger.
PMID- 9641705
TI - Do children with primary nocturnal enuresis have clinically significant behavior
problems?
AB - OBJECTIVE: To determine if primary nocturnal enuresis (PNE) is accompanied by
significant behavioral comorbidity. DESIGN: A survey design using a standardized
behavioral rating scale. SETTING: Behavioral pediatric clinics in the Midwest.
PARTICIPANTS: Subjects with PNE (n=92) were selected from 122 consecutive
referrals for enuresis. Criteria included age 5 years or older, PNE status, and
wetting frequency of at least once per week. The clinical sample without PNE
(n=92) was randomly selected from 429 consecutive referrals to the same pediatric
clinics, stratified for age and sex. The nonclinical sample (n=92) was randomly
selected by strata from the standardization sample (N=614) of the behavioral
checklist used in the study. MAIN OUTCOME MEASURE: The Eyberg Child Behavior
Inventory (ECBI), a standardized parent report scale, was used to measure the
degree of behavioral comorbidity. The ECBI yields 2 scores, Problem Intensity and
Problem Number. RESULTS: Results from 2 separate 3 (group) x 2 (sex) analyses of
variance indicated a significant main effect for group on Problem Intensity and
Problem Number (P<.001). For Problem Intensity, post hoc comparisons indicated
the mean of the PNE sample was significantly higher than the mean of the
nonclinical sample (P<.05), but the mean scores of the clinical sample were
significantly higher than those of both the PNE and nonclinical samples (P<.05).
For Problem Number, post hoc comparisons revealed the means of the PNE and
nonclinical samples did not differ from each other (P>.05) but were lower than
the mean of the clinical sample (P<.05). CONCLUSION: Primary nocturnal enuresis
does not present with significant behavioral comorbidity in most cases. The
results suggest that, with the exception of an extraordinary clinical
presentation, pediatricians should treat PNE as a common biobehavioral problem
without a psychiatric component.
PMID- 9641706
TI - Sudden infant death with external airways covered: case-comparison study of 206
deaths in the United States.
AB - OBJECTIVE: To study factors associated with sudden infant deaths occurring with
the external airways (ie, nose and mouth) covered by bedding. DESIGN: Case
comparison study of infants dying with vs those dying without the external
airways covered. SETTING: Death-scene investigation and reconstruction at the
site of death using an infant mannequin; 18 metropolitan areas. PARTICIPANTS:
Caregivers for a consecutive sample of infants who died of sudden infant death
syndrome (SIDS). Complete data from 206 of 382 eligible cases. MAIN OUTCOME
MEASURES: Among infants dying suddenly and unexpectedly, an analysis of whether
sociodemographic risk factors for SIDS, sleep practices, or bedding increased the
risk of dying with the external airways covered. RESULTS: Data were analyzed by
using univariate and 2 types of multivariate risk analysis, logistic regression
and latent class. Of the victims, 59 (29%) were found with the external airways
covered. Conventional risk factors for SIDS did not affect the risk of death with
the external airways covered. Factors increasing the risk of death with the
external airways covered included prone sleep position (odds ratio [OR], 2.86)
and using soft bedding (OR, 5.28), such as comforters (OR, 2.46) and pillows (OR,
3.31). Infants at low risk for death with the external airways covered slept in
the prone position, but rarely on a pillow, comforter, or other bedding that
allowed a pocket to form beneath the face. All 9 infants who were positioned
supine or on one side for sleep and found with the external airways covered had
turned and were found dead in the prone position. CONCLUSIONS: Sudden infant
deaths with the external airways covered were common in the United States when
most infants slept prone. Soft bedding, including pillows and comforters,
increased the risk that an infant who died would be found with the external
airways covered. Therefore, these items should not be placed near infants,
regardless of the sleep position.
PMID- 9641707
TI - Accuracy and reproducibility of blood lead testing in commercial laboratories.
AB - OBJECTIVE: To assess the proficiency of commercial laboratories in analyzing lead
in clinical blood samples from subjects without overt lead exposure. DESIGN: We
submitted masked duplicate blood lead specimens to 8 masked laboratories. Each
laboratory received blood aliquots immediately following drawing (time 1) and 2
weeks later (time 2) from 7 human subjects and 3 bovine blood samples with known
lead levels of 0.26, 0.57, and 0.79 micromol/L (5.4, 11.8, and 16.4 microg/dL).
Of the 8 laboratories, 5 were commercial laboratories, 1 was a state laboratory,
1 was a research laboratory, and 1 was the Centers for Disease Control and
Prevention reference laboratory. OUTCOME MEASURES: Correlation coefficients were
calculated, and differences within and between laboratories were assessed by
analysis of variance. RESULTS: Results were obtained for all specimens, with all
the human subjects' overall mean lead levels being less than 0.48 micromol/L (<10
microg/dL). Each laboratory reported all human blood specimens appropriately, as
having lead levels less than 0.48 micromol/L (<10 microg/dL) and within 0.14
micromol/L (3 microg/dL) of the overall mean for that subject. All internal
reproducibilities were very high (range, 0.92-1.00) except for one (0.60),
possibly lower because of 1 pair of specimens. Mean differences between blood
samples analyzed at time 1 and time 2 ranged from -1.4 to 1.2, with only 2
laboratories having significant differences (P<.01). CONCLUSIONS: Overall, there
was strong reproducibility within and among laboratories, with no overall time
trend or interlaboratory or intralaboratory variance. The storage conditions did
not seem to affect the aggregate results. The data suggest that through
implementation of the Centers for Disease Control and Prevention/Wisconsin Blood
Lead Proficiency Testing Program, the Centers for Disease Control and
Prevention's Blood Lead Laboratory Reference System, and mandated federal and
state proficiency programs, laboratories in this geographic region have improved
their performance as compared with previous published studies and an unpublished
study.
PMID- 9641708
TI - Compliance with universal precautions among pediatric residents.
AB - BACKGROUND: There are few data on the rate of compliance with universal
precautions among pediatricians. We hypothesized that compliance in pediatrics
would be poor because of the intrinsic difficulties in performing invasive
procedures in small subjects. DESIGN: Prospective, observational study. SETTING:
Tertiary care children's hospital. STUDY PARTICIPANTS: A convenience sample of
pediatric house staff. MAIN OUTCOME MEASURES: Pediatric house staff members were
observed while performing invasive procedures. Procedure type, number of attempts
required, and patient's age and diagnosis were recorded. Degree of compliance
with universal precautions was judged by means of Centers for Disease Control and
Prevention guidelines. Comparisons between the compliant and noncompliant groups
were analyzed by chi2 and 2-tailed t test. RESULTS: A total of 128 procedures
performed by 43 house officers, 4 advanced medical students, and 3 chief
residents or fellows were observed. Sixty-nine (53.9%) of the 128 procedures were
performed correctly according to universal precaution guidelines. Rate of
compliance did not appear to be influenced by small patient size, as judged by
the lack of association with the age of the patient (mean+/-SD, 4.8+/-5.7 years
among those in whom universal precautions were properly used vs 4.9+/-5.4 years
among patients in whom precaution guidelines were breached; P=.96). Moreover, the
number of attempts required in compliant procedures (1.31+/-0.53) was almost
identical to that in noncompliant procedures (1.28+/-0.49; P=.73). Additionally,
compliance did not improve with advanced level of training. CONCLUSIONS: Failure
of compliance among pediatricians has no apparent association with procedure
difficulty, and compliance rates continue to be poor through the course of
pediatric training. These findings underline the need for effective education
concerning universal precautions throughout pediatric residency, and they suggest
that such efforts will not be precluded by obstacles intrinsic to performing
invasive procedures on young subjects.
PMID- 9641709
TI - Autopsies in children: are they still useful?
AB - BACKGROUND: Autopsy has traditionally been the criterion for determining cause of
death and has played a major role in medical education and quality control. With
increasing use of bedside technology, however, autopsy rates have steadily
declined. OBJECTIVE: To identify (1) trends in pediatric autopsy rates during the
past decade, (2) concordance between antemortem and postmortem diagnoses, and (3)
patient characteristics influencing autopsy rates or diagnostic yield. METHODS:
All pediatric deaths between January 1, 1984, and December 31, 1993, were
retrospectively reviewed. Data collection included demographics for all patients,
and length of stay, diagnostic imaging studies, antemortem diagnoses, and autopsy
findings for patients with autopsies. Autopsy diagnoses were compared with
antemortem findings and classified according to their concordance. RESULTS: Of
297 pediatric deaths, autopsies were performed on 107 patients (36%). Autopsy
rates did not change significantly during the study period. Autopsies were not
associated with patient gender, race, or insurance status, but increased
significantly with age. Autopsies were performed in 26% of infants 12 months or
younger, 60% of children between 13 to 60 months of age, and 100% of children 61
months or older (chi2; P <.001). In 34% of cases, new diagnoses were made at
autopsy, including 7 cases where new findings, if known before death, would
likely have resulted in a change in treatment or improved survival. There was no
relationship between new findings at autopsy and age, length of hospital stay, or
antemortem imaging studies. CONCLUSIONS: Autopsy can provide additional
information in more than one third of pediatric deaths. Pediatric autopsy
continues to provide clinically significant data and remains a valuable tool in
modern pediatric practice.
PMID- 9641710
TI - Health status of pediatric refugees in Portland, ME.
AB - BACKGROUND: An understanding of the health conditions affecting pediatric
refugees is essential to providing responsible health care for them when they
arrive in the United States. OBJECTIVE: To assess the health status of pediatric
refugees in an area of increased refugee resettlement. DESIGN: Retrospective
medical records review. SETTING: Ambulatory clinic at Maine Medical Center in
Portland, a community and referral hospital. PATIENTS: One hundred thirty-two
refugees and immigrants aged 2 months through 18 years who had initial health
care evaluations during 1994 and 1995. RESULTS: Sixty-six patients arrived from
Africa, 22 from the former Yugoslavia, and the remainder from the former Soviet
Union, Middle Asia, Southeast Asia, and Latin America. The mean age of the
patients was 10 years; 56 (42.4%) were female. The overall health status of most
of the children was good, with most having appropriate weight and height for age.
Dental caries and dermatologic conditions were the most prevalent findings on
physical examination. Two patients had evidence of traumatic injuries. The
results of tuberculin (Mantoux) tests were positive (> or =10 mm) in 45 (35.2%)
of 128 children for whom results were noted, hepatitis B surface antigen was
detected in 5 (4.0%) of 124 children, and hepatitis B surface antibody was
detected in 26 (21.1%) of 123 children. Five (16.7%) of 30 children younger than
6 years had elevated blood lead levels; anemia was detected in 25 (19.7%) of 127
children with hematocrit results available. Stool specimens were obtained from 87
patients, of whom 38 (43.7%) had pathogenic parasites in at least 1 specimen.
CONCLUSIONS: Pediatric refugees arrive in the United States with a variety of
conditions that may be unfamiliar to practitioners trained in this country. The
results of this study support the screening of refugees from Africa and other
regions for tuberculosis, stool parasites, and hepatitis B.
PMID- 9641711
TI - Distress symptoms among urban African American children and adolescents: a
psychometric evaluation of the Checklist of Children's Distress Symptoms.
AB - OBJECTIVES: To explore the factor structure of the Checklist of Children's
Distress Symptoms (CCDS); to examine whether there is a higher-order single
construct underlying the CCDS measure; and, to assess the association between
children's distress symptoms, as reflected by the CCDS factors, and children's
self-reported exposure to community violence (both victimization and witness
events). DESIGNS: Community-based cross-sectional survey. SETTINGS: Ten public
housing developments in an eastern metropolis. PARTICIPANTS: A total of 349 low
income urban African American children and adolescents (198 males; 151 females),
9 through 15 years of age. MEASURES: Children's distress symptoms, exposure to
community violence, and selected demographic information including parental
education, parental employment status, perceived health status, and school
performance. ANALYSIS: Exploratory factor analysis was performed to determine the
factorial structure of the CCDS measure. Second-order confirmatory factor
analysis was performed to determine if there is a higher-order single underlying
construct among CCDS factors. Pearson correlation coefficients were computed to
assess the relationship between exposure to violence and CCDS factors. MAJOR
FINDINGS: The exploratory factor analysis yielded a 6-factor solution for the
CCDS measure with satisfactory internal consistency. The confirmatory factor
model with a single second-order construct yielded a good fit to the data. In
general, youth who experienced violent victimization or witnessed violent events
reported higher levels of distress symptoms than those who did not. Distress
symptoms labeled as "intrusive thoughts," "distraction," and "lack of
belongingness" were most frequently associated with exposure to violence.
Distress symptoms did not differ on the basis of sex or age. CONCLUSIONS: The
CCDS has utility as a measure of distress symptoms among urban African American
children and adolescents. Whereas analysis provided support for a single higher
order construct, using the proposed 6-factor structure should enhance our
understanding of the psychological impact of exposure to violence on youth and
contribute to more effective intervention efforts.
PMID- 9641712
TI - Group well-child care for high-risk families: maternal outcomes.
AB - OBJECTIVE: To determine if participation in group sessions as part of health
supervision visits for infants improves outcomes compared with individual visits
in high-risk mothers. STUDY DESIGN: Randomized controlled clinical trial.
PARTICIPANTS: Mothers of young infants who had at least 1 of the following risk
factors: aged younger than 20 years at delivery, participation in Medicaid, less
than a high school education, previous or ongoing substance abuse, or history of
abuse as a child. SETTING: Two urban university pediatric clinics in Seattle,
Wash. INTERVENTIONS: Mother-infant dyads were randomized to receive group well
child care (GWCC) or individual well-child care (IWCC) before the infant was 4
months old; the intervention continued until the child was 15 months old. Mothers
completed the Sense of Competence and Social Isolation subscales from the
Parenting Stress Index and Sarason's Social Support Questionnaire at enrollment
and again on completion of the study. During the 11-month study period, 7 health
supervision visits were scheduled for each mother-infant dyad. Social workers met
periodically with mothers during the study and assessed the following functional
outcomes: return to school, return to work, enrollment in a substance abuse
treatment program, and becoming pregnant. In addition, data on study children
were collected from Child Protective Services to assess referrals because of
suspected abuse and/or neglect. RESULTS: Data were collected on 213 mother-infant
dyads, including 108 who received GWCC and 105 who received IWCC. At the
conclusion of the study period, similar proportions of GWCC and IWCC mothers
scored in the high-risk range on the Sense of Competence subscale, Social
Isolation subscale, and the Social Support Questionnaire (P=.57, .32, and .59,
respectively). For more than 50% of the mothers, scores on the Sense of
Competence and Social Isolation subscales deteriorated during the study period
from the not-high-risk range to the high-risk range, regardless of assignment to
GWCC or IWCC. No differences were noted between GWCC and IWCC mothers for any
functional outcome. During the study period, 8.8% of children receiving GWCC were
referred to Child Protective Services vs 8.3% of those receiving IWCC (P=.85).
CONCLUSION: The format of well-child care may not be an important determinant of
outcomes among high-risk mothers.
PMID- 9641713
TI - The physicians' office laboratory: 1988 and 1996 survey of Illinois
pediatricians. Pediatric Practice Research Group.
AB - OBJECTIVES: To contrast practices of physicians' office laboratories in the years
1988 and 1996 and ascertain physicians' perception of the effect of the Clinical
Laboratory Improvement Amendments of 1988 (CLIA). DESIGN: Mailed surveys to
members of the Illinois chapter of the American Academy of Pediatrics in 1988 and
1996. SUBJECTS: There were 525 and 980 respondents in 1988 and 1996,
respectively; analyses included 282 and 374 surveys representing offices where
direct patient care was provided in a nonhospital setting. A paired analysis was
also conducted on 101 offices that responded to both surveys. RESULTS: There was
a decline from 1988 to 1996 in the percentage of offices doing in-office
laboratory testing (93% to 84%, respectively; chi2 test; P<.01) and median number
of types of tests (6 tests vs 4 tests; Mann-Whitney U test; P<.001). Decreases
(chi2 test; P<.01) were seen in the proportion of offices offering throat culture
for group A streptococci (63% to 33%), urinalysis (54% to 33%), urine culture
(53% to 22%), rapid hemagglutination slide test for mononucleosis (42% to 17%),
theophylline level (27% to 4%), and total cholesterol (22% to 13%). The
proportion of offices offering urine dipstick, hematocrit or hemoglobin, complete
blood cell count, and stool occult blood tests remained stable. For solo
practitioner offices only, streptococcal antigen detection testing decreased (66%
to 39%; chi2 test; P<.001). Findings in the paired analyses were similar. In
1996, more offices participated in a formal proficiency testing program (60% vs
11%; chi2 test; P<.001). The CLIA guidelines were deemed responsible for
increased documentation (58%), discontinuing 1 or more tests (56%), increased
frequency of quality control (50%), joining a proficiency program (40%), and
increased cost to patients (32%). CONCLUSIONS: These surveys provide large-scale
data concerning change in office-based laboratories of physicians serving
children during an 8-year period. Office laboratories reduced their menu of tests
and enhanced documentation and quality control for the tests that were done. Data
like these in multiple specialties over time contribute to a comprehensive
picture of the effects of CLIA on office laboratory practices.
PMID- 9641714
TI - Treatment of the acute crisis in maple syrup urine disease.
AB - BACKGROUND: The acute crisis of metabolic decompensation in maple syrup urine
disease is a potentially lethal medical emergency that requires reduction in
concentrations of leucine and other branched-chain amino acids in plasma.
Experience with intravenous mixtures of amino acids indicates that this can be
accomplished by the synthetic forces of protein synthesis. However, these
intravenous mixtures are not generally available. OBJECTIVE: To develop enteral
mixtures suitable for administration by nasogastric drip in minimal volume.
DESIGN: Mixtures of amino acids were designed containing no leucine, isoleucine,
or valine for administration by nasogastric drip. Needs for water and calories
were to be met intravenously. They were designed to be used in the management of
the acute crisis. SETTING: Inpatient pediatric service. PATIENTS: Two patients
with maple syrup urine disease. Data were collected during the management of 3
episodes of metabolic imbalance. INTERVENTION: Studies were carried out for 4 to
11 days, during which there was no intake of leucine. Four different mixtures
were used and a fifth was designed on the basis of this experience. MAIN OUTCOME
MEASURES: Effects on the concentrations of leucine and the other branched-chain
amino acids. Clinical status closely mirrored the concentration of leucine.
RESULTS: In each instance, a progressive fall in leucine concentration was
obtained. Rates of fall were comparable to those obtained with intravenous
therapy. Concentrations of isoleucine fell to levels that made this amino acid
limiting for protein synthesis and hence therapeutic effect. This led to greater
and earlier supplementation with isoleucine. Valine supplementation was also
useful. CONCLUSIONS: The acute crisis of metabolic imbalance in maple syrup urine
disease may be effectively treated by the continuous intragastric drip of
solutions of amino acids devoid of leucine along with provision of water and
calories intravenously.
PMID- 9641715
TI - Radiological case of the month. Neonatal gastric perforation.
PMID- 9641716
TI - Picture of the month. Bilateral nasal septal hematomas.
PMID- 9641717
TI - Pathological case of the month. Erythropoietic protoporphyria.
PMID- 9641718
TI - Professional identity and its responsibilities.
PMID- 9641719
TI - Hegel, the Nazis, and child euthanasia.
PMID- 9641720
TI - Sitting at the top of the slope.
PMID- 9641721
TI - Bulging anterior fontanel.
PMID- 9641722
TI - Varicella vaccination in a primary care pediatric practice.
PMID- 9641723
TI - The Physicians' Desk Reference should not be held as a legal standard of medical
care.
PMID- 9641724
TI - Views on growth hormone treatment in idiopathic shortness of stature.
PMID- 9641725
TI - The genetics of nocturnal enuresis: a simple question of complexity.
PMID- 9641726
TI - Drug prescribing for children in general practice.
PMID- 9641727
TI - Adhesion inhibitory activity of beta-lactoglobulin isolated from infant formulae.
AB - Beta-lactoglobulin was isolated from infant formulae that were ultra high
temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated
beta-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to
human ileostomy glycoproteins was studied in vitro. Beta-lactoglobulin isolated
from sterilized formulae was found to perform significantly less well than
preparations from spray-dried formulae (p = 0.05). Great heterogeneity was
observed in the adhesion inhibitory capacity of beta-lactoglobulin isolated from
UHT-treated formulae. Therefore, no significant difference was observed between
UHT-treated and sterilized formulae or spray-dried formulae (p > 0.10). It can be
hypothesized that beta-lactoglobulin from spray-dried and some UHT-treated infant
formulae may affect the colonization of mucous membranes by E. coli strains
causing neonatal septicaemia and meningitis.
PMID- 9641728
TI - Influence of weight, age and puberty on bone size and bone mineral content in
healthy children and adolescents.
AB - The biology of bone mineralization during growth is important for peak bone mass.
The aim of the study was to examine how body size, age and puberty influence bone
size and bone mineral density. Whole body bone area (BA) and bone mineral content
(BMC) were examined by dual-energy X-ray absorptiometry (Hologic 1000/W) in
healthy girls (n = 201) and boys (n = 142) aged 5-19 y. The influence of height,
weight, age and puberty on bone mineralization was examined by multiple
regression. Main determinants of BA were height and weight. Bone width,
approximated by BA corrected for height, increased highly significantly with
weight and depended weakly significantly on pubertal stage. Main determinants of
BMC were BA, height, age and pubertal stages. Bone mineral density, approximated
by BMC corrected for BA and height, depended on age and pubertal stage, but not
on weight. Thus skeletal size is mainly determined by body size, while bone
density is determined by age and pubertal stage.
PMID- 9641729
TI - Serum digoxin-like immunoreactive factor in children and its relation to sodium
metabolism.
AB - Serum digoxin-like immunoreactive factor (DLIF), an endogenous substance that
cross-reacts with antidigoxin antibodies, was assessed (fluorescence polarization
immunoassay) in children (n = 134) aged 5-16 y, who had never been treated with
cardiac glycosides. DLIF was found in 50% of serum samples at a mean
concentration of 0.16 +/- 0.06 ng/ml (range 0.03-0.35 ng/ml). Although the study
population as a whole was apparently homogeneous with regard to serum sodium
content, and none had clinical signs of sodium imbalance, children with DLIF
showed significantly lower natraemia (p = 0.0002), higher urinary concentration
(p = 0.001) and fractional excretion (p = 0.001) of sodium, and increased
systolic blood pressure (p = 0.009) compared with children without DLIF. Inverse
correlations were found between DLIF concentration and serum sodium (p < 0.01),
urine sodium content (p < 0.001), 24-h sodium excretion (p < 0.001), systolic (p
< 0.001) and diastolic (p < 0.01) blood pressure. These findings suggest that
sodium handling is different in children with and without DLIF, since this
material seems to be released preferably in subjects who show a trend towards
negative sodium balance. Such an association suggests that DLIF may be a
physiologically relevant material involved in sodium homeostasis.
PMID- 9641730
TI - Exploration of glucose homeostasis during fasting in growth hormone-deficient
children.
AB - In order to define more precisely the risk of hypoglycaemia in GH-deficient
children and to clarify the role of growth hormone (GH) in glucose homeostasis, a
24-h fast was monitored in 10 GH-deficient children aged 1.1-6.5 y. Asymptomatic
hypoglycaemia (blood glucose < or = 2.6 mmol/l) occurred in 9/10 children, 2 of
whom prematurely interrupted the test. Blood glucose profile was not reproducible
between children and had no correlation with age (p = 0.48). Gluconeogenesis was
considered as non-altered as read from the normal plasma lactate and pyruvate
concentrations throughout the test. Plasma ketone body concentrations increased
during the test, but were lower than expected with respect to the decrease of
blood glucose. This suggests insufficient ketogenesis which could exacerbate
hypoglycaemia in GH-deficient children if brain glucose utilization were not
alleviated by ketone body oxidization, as is normally the case. The positive
glucose response after glucagon stimulation in 6/10 patients indicated normal
hepatic glycogen content. However, these responses were unexpected following the
prolonged fast and its concomitant hypoglycaemia, and would therefore tend to
suggest a defect in glycogenolysis. These results confirm the tendency to
hypoglycaemia, even after infancy, in GH-deficient children. These hypoglycaemias
may occur by different types of malfunctioning, such as insufficient ketogenesis
or a defect in glycogenolysis. These hypotheses require confirmation by a more
systematic study of the metabolic and hormonal changes that occur during fasting
in both GH-deficient and normal children.
PMID- 9641731
TI - Three-year data from a comparative study with recombinant human growth hormone in
the treatment of short stature in young children with intrauterine growth
retardation.
AB - Growth acceleration and bone maturation were studied for 3 y in 69 children with
severe short stature and a history of intrauterine growth retardation (IUGR), to
determine the effect of treatment with recombinant human growth hormone (r-hGH).
The patients were enrolled in an open, multicentre trial and were randomly
allocated to either the treated group (Group 1) or the control group (Group 2).
The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067
mg/kg) s.c., during 3 y and the children in Group 2 started the study with a 1-y
observation period followed by a 3-y treatment period. At birth, their mean
weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At
baseline, the patients were prepubertal, non-GH deficient, with no known
dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4,
height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of
treatment, linear HV in Group 1 increased in comparison with the pre-treatment
period (from 5.7 +/- 2.0 to 10.1 +/- 1.7 cm/y; p < 0.001) and with the first year
of observation in Group 2 (p < 0.001). Increased HV was sustained during the
second and third year of treatment and was significantly higher than at baseline.
A similar growth pattern was seen during the 3 y of GH treatment in Group 2. Mean
height SDS for chronological age increased by 2.0 +/- 0.7 in the two groups after
3 y of treatment. HV after 1 y of treatment was negatively correlated with growth
velocity at baseline. Bone age remained retarded but increased with a mean of
almost 4 y after 3 y of treatment in both groups. Even at a dose that is three
times the replacement dose treatment with r-hGH was well tolerated. From these
results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up
growth in young children with severe short stature and a history of IUGR. Long
term studies are needed to assess ultimate effects on final height.
PMID- 9641732
TI - Once versus twice daily injections of growth hormone in children with idiopathic
short stature.
AB - The aim of this study was to compare the growth response of 22 short pre-pubertal
children without growth hormone deficiency, treated with a single daily growth
hormone injection (group A), to the growth response of 27 similar children,
treated with the same daily dose divided into 2 subcutaneous injections per day
(group B), for 1 y, in a randomized study. GH treatment significantly promoted
growth parameters, height standard deviation score and height velocity standard
deviation score in both groups. Serum insulin-like growth factor I was also
increased. There were no significant differences in growth response, serum IGF-I
levels, or the advance in bone age between the two study groups after 1 y of GH
therapy. We conclude that twice daily s.c. growth hormone injections provide no
advantages over once daily injection of the same dose in promoting the linear
growth of short children without growth hormone deficiency.
PMID- 9641733
TI - Adult height comparison between boys and girls with precocious puberty after long
term gonadotrophin-releasing hormone analogue therapy.
AB - We examined 22 girls and 11 boys with idiopathic precocious puberty (IPP) treated
with a GnRH analogue for a period of about 4 y. The purpose of our study was to
evaluate possible differences between the two sexes in bone growth and skeletal
maturation during treatment and in the achievement of final height, and also to
study the relative contribution of particular hormones--sex steroids, DHEAS, GH
and IGF-I--during the pubertal growth spurt. At the beginning of therapy mean
chronological age (CA) was 7.61 +/- 0.84 y in boys and 7.32 +/- 1.06 y in girls.
After the first year of treatment, growth velocity and delta bone age/delta
chronological age (deltaBA/deltaCA) ratio had declined significantly in both
groups. At the end of therapy we observed a statistically relevant increase in
predicted adult height in both sexes, with a more appreciable mean gain
(expressed as SDS) being achieved by male patients. During the first year
following discontinuation of treatment, a significant increase in the
deltaBA/deltaCA ratio was observed in both males and females; by contrast, growth
velocity increased only in male patients. Adult height SDS was thus greater in
boys (0.13 +/- 0.91) than in girls (-0.62 +/- 0.88, p < 0.05). With regard to
endocrinological data, oestradiol and testosterone were significantly reduced
during the first year of therapy, while DHEAS levels increased slightly in both
sexes throughout the course of treatment. GH peak after clonidine and IGF-I
concentrations remained unchanged in both groups. Also, a study of nocturnal GH
secretion (10 subjects) showed no noteworthy decrease in any of the patients,
whether in terms of mean GH, of the sum of pulse amplitudes, or of pulse
frequency. In conclusion, our data indicate that boys achieve more significant
results in terms of adult height than girls. With reference to endocrinological
data, the effect of sex steroids on bone maturation seems to be more significant
than previously thought, and we hypothesize a different role for androgens and
oestrogens in regulating height velocity and bone maturation in both male and
female subjects during pubertal growth spurt.
PMID- 9641735
TI - Ketoacidosis occurring in newly diagnosed and established diabetic children.
AB - A 6-y retrospective case note review was performed to determine the causes of
ketoacidosis. 135 patients and 463 diabetic years were involved. Fifty-two
ketoacidosis episodes occurred: 19 episodes in new patients and 33 episodes in 19
patients with established diabetes. 27% of newly diagnosed patients presented in
ketoacidosis. They were similar in terms of age, sex and proportion living in
single parent families to those presenting without ketoacidosis. The 33
ketoacidosis episodes occurring in established patients included 12 episodes in 3
children who were transferred to our care because of uncontrolled diabetes.
Insulin omission was the cause of ketoacidosis in 9/19 (47%) patients, and was
suspected in a further 5/19 (26%). Family and school problems were common and
14/19 patients came from single parent families. Established patients aged > or =
11 y were predominantly female (10F, 2M), whereas patients aged < or = 10 y were
predominantly male (6M, 1F). 7 patients with multiple ketoacidosis episodes were
all > or = 11 y and 6 were female. Families with > or = 2 diabetic children
appeared vulnerable, 4 cases coming from 3/7 such families.
PMID- 9641734
TI - Midline brain lesions in children with hormone insufficiency indicate early
prenatal damage.
AB - The relationships between midline brain morphology, anterior visual pathway
morphology and hormonal status in children with impaired growth were studied.
Intracranial morphology was studied by magnetic resonance imaging in 47 children
(14F, 33M), median age 9.7y (range 2.6-18.7y) undergoing growth hormone treatment
(GH; 0.1 U/kg/d). They were chosen to represent various birth sizes and a
spectrum of hormone insufficiencies. There was a relationship between GH
secretion and the morphology of the neurohypophysis, the pituitary stalk and the
anterior visual pathways, i.e. the greater the GH insufficiency, the more
abnormal were these structures. The children with anterior visual pathway
abnormalities had the lowest GH levels and the smallest adenohypophysis. The
association between abnormalities of the anterior visual pathways and the
hypothalamo-pituitary structures may reflect a common prenatal neural damage in
embryologically and anatomically closely related structures.
PMID- 9641736
TI - Transient focal neurologic deficits associated with hypoglycaemia in children
with insulin-dependent diabetes mellitus. Italian Collaborative Paediatric
Diabetologic Group.
AB - We describe 54 transient focal neurologic deficits (TFND) episodes in 44 children
under 18 y observed retrospectively during a 5-y period (1991-96). Mean age and
duration of insulin-dependent diabetes mellitus (IDDM) were 8.4 and 3.4 y,
respectively. None of the children had a history of seizure disorder and only one
had a personal history of migraine. Twenty-nine episodes were characterized by
right- and 25 by left-sided hemiparesis. Three of six patients who presented more
than one event had alternate episodes of right- and left-sided hemiparesis. On 8
occasions the episode was preceded by a brief convulsion, in 39 it was not
witnessed, and in 7 it was certainly absent. Hypoglycaemia (< or = 2.77 mmol/l)
was documented on 26 occasions. On 18 of these 26 occasions, the episodes did not
resolve promptly after sugar administration. The clinical course was benign, all
patients remained neurologically normal and none developed migraine at follow up.
Episodes of TFND were associated with hypoglycaemia in the majority of our cases
and we do not consider invasive investigations to be mandatory, since the long
term prognosis was invariably good.
PMID- 9641737
TI - Normal growth of prepubertal nephrotic children during long-term treatment with
repeated courses of prednisone.
AB - The growth of 21 prepubertal children with steroid-dependent frequently relapsing
nephrotic syndrome was studied before and during treatment with repeated courses
of oral prednisone for 4 y. The height and height velocity standard deviation
scores (HSDS and HVSDS) of the nephrotic children were -0.11 and -0.06,
respectively, at the onset of the disease and -0.12 and +0.05, +0.14 and +1.02,
+0.21 and +0.78 and +0.17 and +0.66, respectively, thereafter yearly during the
treatment. The mean yearly cumulative dose of prednisone was 6300, 3459, 2677 and
2081 mg/body area (m2) at the first, second, third and fourth year, respectively.
The nephrotic children grew normally for their age before onset of the disease
and growth remained normal despite prednisone treatment.
PMID- 9641738
TI - Incidence rate of first-time symptomatic urinary tract infection in children
under 6 years of age.
AB - A retrospective population-based study was performed to describe the incidence
rate of first time symptomatic urinary tract infection in children under 6 y of
age. A total number of 299 children was identified during the 20-month study
period in a population of 20,000 girls and 21,000 boys. The cumulative incidence
rate during the first 6 y of life was 6.6% for girls and 1.8% for boys. The
annual incidence rate in girls of urinary tract infection/1000 at risk was
between 9 and 14 for each of the six 1-y age intervals. In girls, the proportion
of febrile urinary tract infection was high during the infant year, while girls
older than 2 y most often had non-febrile infection. For infant boys, the
incidence rate and the proportion of febrile urinary tract infection were
comparable to that of girls, while after the first year of life urinary infection
of any kind was rare, with an incidence rate of 1-2/1000 at risk.
PMID- 9641739
TI - Effects of a proton-pump inhibitor in cystic fibrosis.
AB - Most children with cystic fibrosis (CF) show persisting steatorrhoea even when
treated with pancreatic enzyme. As a low duodenal pH could be responsible for
this persisting fat loss, we evaluated the effects of a proton-pump inhibitor
(lansoprazole) on both steatorrhoea and growth parameters in 15 CF patients, aged
3.1-22.6 y. Acid steatocrit, anthropometry and dual-energy X-ray absorptiometry
were used to evaluate steatorrhoea and the nutritional status before, during and
3 months after stopping lansoprazole treatment (15 mg/d for 3 months). Mean +/-
SD acid steatocrit values decreased from 37.1 +/- 8.8% to 28.5 +/- 10.6% (p =
0.02). Significant mean Z-score improvements were found for weight (+0.14; p =
0.02), height (+0.15; p = 0.03), subscapular (+0.61; p = 0.003), supra-iliac
(+0.8; p = 0.002) and the sum of the four measured skinfolds (+0.61; p = 0.002).
Z-scores deteriorated again after stopping lansoprazole. Fat mass and bone
mineral content increased significantly on lansoprazole (p = 0.008 and p = 0.005,
respectively). We conclude that lansoprazole as adjuvant therapy significantly
improves both steatorrhoea and the nutritional status in CF children who maintain
steatorrhoea while on pancreatic enzymes.
PMID- 9641740
TI - Serum inflammatory markers and effects of age and tobacco smoke exposure in young
non-asthmatic children.
AB - Serum eosinophil cationic protein (ECP), but not serum myeloperoxidase (MPO), has
been found to reflect disease activity of asthma and eczema, but no reference
values exist for young children. Thus, we aimed to provide values of serum-ECP
and serum-MPO in young children without obstructive airways disease (OAD), and
determine possible influencing factors. Parental interview was performed and
serum was collected from a total of 245 children (207 children aged 24-41 months
and 76 children aged 0-23 months) with no history of lower respiratory disease.
Repeated serum samples were obtained in 38 subjects. Ten percent of the children
had active eczema at examination. All children were controls in the "Environment
and Childhood Asthma" study in Oslo. Geometric means (GM +/- 1.96 SD) for serum
ECP were 11.8 microg/l (2.5-56.0) and 7.9 microg/l (2.0-30.4), respectively, in
the 0-23 and 24-41-month-old children, with the corresponding values for serum
MPO 453 microg/l (153-1349) and 347 microg/l (142-859), respectively. Age was
inversely associated with serum-ECP and serum-MPO, most pronounced in the
youngest children. Active eczema and maternal daily smoking adversely affected
serum-ECP, but not serum-MPO. Gender and parental atopy did not influence the
results. We conclude that serum-ECP in very young children is influenced by age
and active eczema and is related to maternal smoking in a dose-dependent fashion.
These factors should be considered when assessing inflammatory markers in very
young children.
PMID- 9641741
TI - Factors affecting cognitive, motor, behavioral and executive functioning in
children with phenylketonuria.
AB - We administered measures of cognitive, frontal lobe (executive), behavioral and
motor functioning to 18 children with classical phenylketonuria, aged 12-101
months, in order to determine the relationship of age, current and lifetime
average phenylalanine levels, and individual variation (standard deviation of
lifetime average levels) to these functions. On measures of cognitive function,
in children > or = 3 y of age lower current phenylalanine levels were associated
with higher cognitive functioning. On a behavioral temperament scale designed for
normal children, we found that higher current and average phenylalanine levels
correlated with more difficult temperament. Motor function was also poorer in
children with phenylketonuria, and was most impaired in children with current
phenylalanine levels >360 micromol/l. We also identified a previously unreported
correlation between increased individual variation and poorer executive function
performance, a finding that may raise new management concerns about level
fluctuations. Maintenance of phenylalanine levels <360 micromol/l may be
necessary for optimal performance in children with phenylketonuria.
PMID- 9641742
TI - Molecular genetics of nocturnal enuresis: clinical and genetic heterogeneity.
AB - Forty-two children with nocturnal enuresis (27 with primary, 4 with secondary
nocturnal enuresis and 11 with combined primary nocturnal enuresis and daytime
wetting) were selected retrospectively from a study of 167 consecutive children
with enuresis. The aim of the study was to collect formal genetic data, perform
molecular genetic linkage-analyses with five microsatellite markers on
chromosomes 13q, 12q or 8q and specify the associations between genetic findings
and clinical, as well as psychiatric diagnoses. Positive linkage of nocturnal
enuresis to one of the microsatellite markers was possible in 27 children from 23
families and was not possible in 15 children. Somatic findings in both the groups
with and without possible assignment of nocturnal enuresis to a marker were
heterogeneous. Psychiatrically, a low rate of behavioural problems was apparent.
These findings support the hypothesis of genetic and phenotypical heterogeneity
of nocturnal enuresis, without linkage of specific psychiatric and somatic
phenotypes to certain chromosome markers.
PMID- 9641743
TI - Disease of the liver following bone marrow transplantation in children:
incidence, clinical course and outcome in a long-term perspective.
AB - Sixty-four consecutive cases of allogeneic (n = 16), autologous (n = 47) or
syngeneic (n = 1) bone marrow transplantation (BMT) in children with
haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed
to assess the incidence, clinical presentation and outcome of liver disease.
Median follow-up time was 5 y (1.0-10). No liver diagnosis was established at the
pre-transplant check-up. During the first 100 d post-transplant, 81% of the
patients had impaired liver function as documented by various biochemical
parameters. Three of 64 patients (5%) met diagnostic criteria for veno-occlusive
disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute
graft vs host disease (GVHD) with liver involvement (grades II-III). No patient
died of liver disease. During the late post-transplant follow-up, one patient
developed HCV hepatitis after packed erythrocyte transfusion. Four patients were
diagnosed as having chronic GVHD with liver involvement; three of them also had
an episode of CMV hepatitis. At their latest follow-up, the patients with chronic
GVHD had aminotransferase values 1.5-3 times the normal, whereas all other long
term survivors had normal or near-normal liver function tests. We conclude that
the incidence of serious liver disease was low in this paediatric population of
bone marrow recipients.
PMID- 9641744
TI - Foetal supraventricular tachycardia treated with sotalol.
AB - This retrospective study (1991-95) presents our experience with sotalol in the
treatment of 14 foetuses with supraventricular tachycardia (SVT). SVT was
diagnosed in a structurally normal heart at a gestational age of 24-35 (median
28) weeks. In eight foetuses, hydrops was evident at presentation. In all
patients pharmacological conversion with digoxin was tried before sotalol
treatment was started. Sotalol was given orally to the mothers in a dose of 80
160 mg x 2. Cardioversion was obtained in 10 foetuses. In seven of these patients
re-entry tachycardia and in five pre-excitation could be documented after birth.
In two foetuses not responding to sotalol a long RP tachycardia was demonstrated;
even when using digoxin, sotalol, flecainide and/or propafenone in different
combinations after birth complete suppression of the arrhythmia was not obtained.
Two severely hydropic foetuses died 1 and 10 d, respectively, after starting with
sotalol. The 12 surviving infants were doing well except for one infant, with a
cerebral lesion probably related to the arrhythmia. These findings demonstrate
that sotalol can be useful in the treatment of foetal SVT.
PMID- 9641745
TI - Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of
newborn infants.
AB - The aim of this study was to evaluate the cerebral synthesis of eicosanoids in
the asphyctic newborn and to investigate the relation between the prostanoid
profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic
ischaemic encephalopathy (HIE). Levels of 6-keto-PGF(1-alpha), TXB2, PGE2 and
PGF(2-alpha), in CSF were measured in 40 full term newborns during the first day
of life. Thirty of these newborns had birth asphyxia and were divided into three
groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They
were compared to a control group of 10 non-hypoxic newborns. Determinations of
the metabolites in CSF were performed by RIA and expressed as pg/ml (mean +/-
SD). The CSF TXB2 (thromboxane A2 metabolite) in asphyxiated newborns was always
higher than in the control group (28.12 +/- 10.6), and related to the severity of
HIE (p = 0.005): without HIE (50.84 +/- 16.4; p = 0.02), mild HIE (80.65 +/-
12.64; p < 0.01) and moderate-severe HIE (178.14 +/- 20.5; p < 0.01). The CSF 6
keto-PGF(1-alpha) (prostacyclin metabolite) in asphyxiated newborns was always
higher than in the control group (80.55 +/- 12.56), but indirectly related to the
severity of HIE: without HIE (240.95 +/- 28.12; p < 0.01), mild HIE (183.65 +/-
30.1; p < 0.01) and moderate-severe HIE (140.55 +/- 25.12; p < 0.01). In the
moderate-severe HIE group, the increase in TXB2 was higher than the rise in 6
keto-PGF(1-alpha).
PMID- 9641746
TI - Bacterial genotype and neurological complications of Escherichia coli O157:H7
associated haemolytic uraemic syndrome.
AB - We examined the possibility of an association between the bacterial genotype of
Escherichia coli O157:H7 and the likelihood of progression to neurological
complications in childhood gastroenteritis-associated haemolytic uraemic syndrome
(D+HUS). Bacterial stool isolates were available from 51 patients with HUS; 11 of
these patients suffered a neurological complication. Bacteria were assessed for
plasmid content, verotoxin (Shiga-like toxin) profile, verotoxin 2 subtype, and
presence of the eaeA (effacement and attachment) marker. No association of
bacterial genotype with central nervous system (CNS) manifestations was observed.
Whilst the cause of CNS manifestations may be multifactorial, there is no
evidence at present to implicate specific bacterial traits.
PMID- 9641747
TI - Prevention of hypoglycaemia in a patient with type Ib glycogen storage disease by
an amylase (alpha-glucosidase) inhibitor.
AB - Patients with type Ib glycogen storage disease (GSD Ib) are susceptible to
hypoglycaemic episodes. To determine whether an amylase (alpha-glucosidase)
inhibitor, voglibose, can be useful in the control of hypoglycaemia, we tried it
in a 14-y-old male with GSD Ib. Oral administration of voglibose prolonged the
duration of normoglycaemia and reduced the incidence of hypoglycaemia attacks.
These findings indicate that voglibose may be useful for preventing hypoglycaemia
in GSD Ib patients.
PMID- 9641748
TI - Optic neuropathy in McCune-Albright syndrome: an indication for aggressive
treatment.
AB - McCune-Albright syndrome consists of the triad polyostotic fibrous dysplasia,
cafe-au-lait spots and autonomous hyperfunction of one or more endocrine systems.
The most frequent neurological complication of craniofacial fibrous dysplasia is
visual loss. We describe a 17-y-old boy with McCune-Albright syndrome and acute
loss of vision in the left eye caused by encroachment of the left optic nerve by
fibrous dysplastic lesions. Neurosurgical intervention improved left eye vision.
Aggressive intervention is indicated in cases of acute visual loss in patients
with craniofacial fibrous dysplasia. This is supported by a review of other
reported cases.
PMID- 9641749
TI - Factitious illness by proxy presenting as anorexia and polydipsia by proxy.
AB - Factitious illness by proxy is a highly pathological form of parent-child
relationship. To our knowledge no former case of polydipsia by proxy has been
published. The case of a 2-y-old boy suffering from malnutrition due to
displacement of maternal anorexia and polydipsia is presented. Child psychiatric
evaluation found cognitive delay and psycho-social impairment in the child, as
well as a severe mother-child relationship disturbance. Psychological assessment
showed a personality disorder with depressive and paranoid features in the
mother. The father was described as a schizoid personality. The possible
mechanisms of displacement are hypothesized.
PMID- 9641750
TI - Colchicine for recurrent pericarditis in children.
AB - The incidence of recurrence of acute pericarditis in children varies from 15% to
30% and is accompanied by a high morbidity. Various treatment modalities have
been used with variable success rates and side effects. La Serna et al. (Lancet
1987; 26: 1517) were the first to treat adults with recurrent pericarditis with
colchicine, and were followed by other authors. To our knowledge no studies in
children have been reported. In this paper, we present three children who
suffered from viral or idiopathic recurrent pericarditis, despite multiple
courses of non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids.
They responded remarkably well to colchicine, which was administered for 6 months
with no adverse reactions. They continue to do well 18, 11 and 12 months after
cessation of treatment, respectively.
PMID- 9641751
TI - Serial chitotriosidase activity estimations in neonatal systemic candidiasis.
PMID- 9641752
TI - Serum malondialdehyde levels in preterm and fullterm infants undergoing
phototherapy.
PMID- 9641792
TI - 'Biological signals' to 'biological signals and receptors'.
PMID- 9641793
TI - Hypothalamic relationships between interleukin-6 and LHRH release affected by
bacterial endotoxin in adult male rats. Involvement of the inhibitory amino acid
system.
AB - Immune system alterations coexist with modifications in the reproductive axis.
The bacterial endotoxin lipopolysaccharide (LPS) has inflammatory effects and
stimulates cytokine release in the hypothalamus where LHRH neurons are located.
LPS inhibition of LHRH release at hypothalamic level appears to be associated
with modifications in the cerebral immune system. Central and peripheral LPS
administration induces the expression and release of several cytokines in the
central nervous system. Hence the present study was designed to investigate a
possible function of the interleukin-6 (IL-6) stimulated by LPS in the regulation
of LHRH secretion. Male rats were decapitated, and the preoptic mediobasal
hypothalamic area (PO/MBH) was dissected and superfused with Earle's balanced
salt solution. Superfusate fractions were collected at 15-min intervals after a
60-min stabilization superfusion period. LPS (100 ng/ml) and IL-6 receptor
antagonist (IL-6ra) were then added to the superfusion medium over 1 h in two
different experimental designs: (1) LPS only and (2) LPS followed by IL-6ra,
performed in different experiments. This was followed by a washout period. The
PO/MBH fragments were then subjected to a 56 mM K+ stimulus. Control PO/MBH
fragments were continuously superfused with Earle's solution. As expected, LHRH
release was significantly reduced (p < 0.05) during and following exposure to
LPS. At the same time, IL-6 concentrations significantly increased in the
superfusion medium compared with the control group. IL-6ra significantly (p <
0.01) potentiated the inhibitory effect of LPS on LHRH secretion. On the bases of
previous papers indicating a stimulatory effect of IL-6 on LHRH release it could
be considered that the potentiation of IL-6ra of the inhibitory effect of LPS on
LHRH could be the consequence of the lack of the stimulatory effect of IL-6 on
LHRH produced by the receptor antagonist. IL-6ra also increased IL-6 levels
measured in medium probably due to a decrease in the metabolization induced by
the blockage of the receptors and the consequent accumulation of IL-6 in the
media. These results could indicate that IL-6 partly attenuates the inhibitory
effect of LPS on LHRH release. These observations indicate that there is an
increase in IL-6 release that becomes significant at the same time when LHRH
release is decreased. Also, depolarizing concentrations of K+ (56 mM) did not
increase IL-6 release, while LHRH release from the hypothalamic fragments was
significantly increased. These data suggest that the inhibitory effect of LPS on
LHRH release may be explained by the stimulation of other cytokines than IL-6,
meanwhile the augmented levels of IL-6 probably released via a nonneuronal source
was shown to be higher when LHRH was decreased. This could confirm the
stimulatory role of IL-6 on LHRH release.
PMID- 9641794
TI - Circadian rhythms in adenohypophysial hormone levels and hypothalamic monoamine
turnover in mycobacterial-adjuvant-injected rats.
AB - The effect of Freund's adjuvant injection on 24-hour variation in circulating
ACTH, prolactin, growth hormone (GH) and thyroid-stimulating hormone (TSH)
levels, and of hypothalamic norepinephrine (NE) content and dopamine (DA) and
serotonin (5HT) turnover was examined in adult rats. In control rats, serum ACTH
and prolactin exhibited peak values at the light-dark transition while the
maximum in TSH was found in the late afternoon. GH levels did not vary on a 24
hour basis. In Freund's-adjuvant-injected rats, 24-hour variations in TSH levels
became blunted while 24-hour variations in prolactin and ACTH persisted. Freund's
adjuvant treatment augmented serum ACTH and prolactin levels, and decreased GH
and TSH levels. Hypothalamic NE content, and turnover of DA and 5HT varied on a
24-hour basis in rats receiving adjuvant's vehicle. The NE content of the
anterior, medial and posterior hypothalamus peaked at 04.00 h, while that of the
median eminence attained its maximum at 16.00-20.00 h. Maxima in hypothalamic DA
and 5HT turnover occurred at 04.00 h regardless of the region examined. In
Freund's-adjuvant-injected rats, reduced amplitude of daily variations of NE
content in the median eminence and anterior and medial hypothalamus, as well as a
phase advance in the 24-hour rhythm of the posterior hypothalamic NE content were
seen. Mycobacterial adjuvant injection also reduced the amplitude of circadian
rhythm in hypothalamic 5HT turnover, shifted the maximum in median eminence DA
turnover towards light-dark transition, and decreased the amplitude of DA
turnover rhythm in the anterior, medial and posterior hypothalamus.
Administration of the immunosuppressant drug cyclosporine restored the augmented
ACTH and prolactin levels and the depressed GH and TSH levels found in Freund's
adjuvant-injected rats. Cyclosporine was also effective to restore 24-hour
rhythmicity of serum ACTH and TSH, but not of prolactin levels. Immunosuppression
restored rhythmicity of NE content and of DA and 5HT turnover in anterior, medial
and posterior hypothalamic regions. Cyclosporine did not modify the effect of
Freund's adjuvant on median eminence but in was able to counteract the changes in
the DA and 5HT turnover in the median eminence found after immunization. The
results are in accord with a significant effect of immune-mediated inflammatory
response at an early phase after Freund's adjuvant injection on ACTH, GH,
prolactin and TSH release mechanisms, which was partially sensitive to
immunosuppression induced by cyclosporine.
PMID- 9641795
TI - Acute and chronic effects of superior cervical ganglionectomy on in vitro
mitogenic responses of lymphocytes from submaxillary lymph nodes of pituitary
grafted rats.
AB - Male rats were grafted an anterior pituitary within breast muscles or received a
sham operation on day 5 of life. At the 60th day of life, the sympathetic
denervation of rat submaxillary lymph nodes was achieved by a bilateral
sympathetic superior cervical ganglionectomy (SCGx; at 15.00 h). Rats were killed
either 18 h later (acute SCGx) or after 12 days (chronic SCGx) to measure
lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced cell proliferation in
submaxillary lymph nodes, submaxillary lymph node cellularity and serum prolactin
levels. In control rats, acute SCGx significantly augmented LPS or ConA activity
on lymph cells while chronic SCGx had no effect. In pituitary-grafted rats, acute
SCGx depressed the mitogenic effect of LPS or ConA whereas chronic SCGx augmented
it. A global inhibitory effect of surgical stress on submaxillary lymph node
cellularity was found in rats subjected to SCGx or its sham operation 18 h
earlier. Serum prolactin levels increased significantly in pituitary-grafted
rats, particularly in those subjected to chronic SCGx. In pituitary-grafted rats,
a significant effect of acute SCGx was apparent, with serum prolactin levels
augmenting about twice in sham-SCGx rats, and to a significantly less extent in
acute SCGx rats. The results provide further evidence of the immunomodulatory
role of local sympathetic nerves in submaxillary lymph nodes.
PMID- 9641796
TI - Cytokine-neurotransmitter interactions in the brain.
AB - The data reviewed in this study show that immune-active molecules, such as
infectious agents and their components, and cytokines, may induce profound
alterations in several neurotransmitters in the CNS. The activation of the immune
system elicits fever, behavioral and neuroendocrine changes and may be involved
in neuropathological changes occurring in CNS conditions. These effects may be
achieved through and accounted for by the changes induced in central
neurotransmitters and in the neuroendocrine system by immune challenges. The
present review will summarize the available evidence of the reciprocal
interactions between cytokines and neurotransmitters in the CNS.
PMID- 9641797
TI - Cytokines and cognitive function in mice.
AB - A bidirectional flow of informations exists between the central nervous system
and the immune system. Cytokines play a crucial role in this communication and
exert several neuromodulatory actions. This short review considers some data
concerning the effects of several cytokines, interleukin (IL)-1, IL-2, IL-6 and
granulocyte-macrophage colony-stimulating factor on scopolamine-induced amnesia
for a passive avoidance response, and on hippocampal neurotransmitter amino acid
levels in mice. We interpret these behavioral and biochemical observations to
indicate that the cytokine-to-brain communication can result in alterations in
brain functions.
PMID- 9641798
TI - Mechanism of action of interleukin-1 in modulating gonadotropin secretion. In
vivo and in vitro studies.
AB - To obtain further information on the mode of action of interleukin (IL)-1 in
modulating gonadotropin secretion, a series of in vivo and in vitro studies has
been performed with the beta-isoform of IL-1. IL-1 beta injected in a lateral
ventricle of 3-week-castrated female rats resulted in the expected decrease in
serum levels of gonadotropins luteinizing hormone (LH), and follicle-stimulating
hormone (FSH), accompanied by a decrease in the number of LH-releasing hormone
(LHRH) receptors. These results may indicate that the inhibition of gonadotropin
release may result from a decrease in the number of LHRH pituitary receptors
either through a direct effect on the pituitary or by modulating the release of
LHRH from hypothalamic neurons able to induce a reduction in pituitary LHRH
receptors. In vitro studies using the GT1-1 cell line, which specifically
produces and secretes LHRH, demonstrated that IL-beta stimulates LHRH release but
does not influence intracellular levels of LHRH mRNA. These results seem to
indicate that IL-1 beta may act at several levels of the nervous machinery
leading to gonadotropin secretion, with a series of effects more complex than
previously anticipated.
PMID- 9641800
TI - Combining ECT and antidepressants: time to reassess.
PMID- 9641799
TI - Melatonin involvement in immunity and cancer.
AB - The most studied endocrine product of the pineal gland, melatonin, has been
reported to be involved in the feedback between neuroendocrine and immune
functions and to exert oncostatic action, at least in certain experimental
conditions. Melatonin seems to be an integral part of the immune system, by
exerting direct and/or indirect stimulatory effects on both cellular and humoral
immunity. Likewise, an antitumor activity of melatonin has been shown in several
experimental models in vivo and in vitro. The means by which melatonin exerts its
effects on immunity and neoplastic growth have not been elucidated. The different
putative mechanisms of action of melatonin investigated so far are here briefly
discussed.
PMID- 9641802
TI - A comparison of visual and computer-generated measures of "seizure quality".
AB - We report on the first direct comparison of measures of seizure quality generated
by visual rating of electroencephalographic (EEG) regularity and postictal
suppression with THYMATRON-DGx computer-generated indices of seizure energy and
postictal suppression. Thirty-two consecutive patients referred for
electroconvulsive therapy (166 consecutive treatments) were studied. Blinded
ratings of seizure duration, regularity, and postictal EEG amplitude suppression
derived from the paper EEG were compared against computer-rated measures of
seizure duration, seizure energy index, mean ictal amplitude, and postictal
suppression. Our results confirm previous findings of high correlations between
computer and visual determinations of seizure duration. Significant differences
were found for computer-derived postictal suppression, seizure energy index and
mean ictal amplitude for different levels of the visual rating scales. Our
results provide preliminary support for the concurrent validity of these
measures.
PMID- 9641801
TI - A comparison of brief and ultrabrief pulse stimuli in unilateral ECT.
AB - A double-blind, randomized, comparative study of the therapeutic efficacy and
side effects of unilateral electroconvulsive therapy (ECT) given with two
different stimulus types was carried out in the Kuffner Sanatorium, Horni
Berkovice, Czech Republic. Brief or ultrabrief pulse stimuli were used in 48
hospitalized patients, ages 17-61 years, diagnosed with either schizophrenia (n =
42) or major depression (n = 6). All patients received eight unilateral
treatments each. Their clinical state and presence of cognitive impairment were
evaluated with a battery of tests and rating scales before ECT, after the last
ECT, and 1 month later. Patients were markedly improved after the course of ECT,
and the improvement was maintained 1 month later. There were no significant
differences in the extent of improvement between the groups treated with brief-
and ultrabrief-pulse stimuli. No deleterious effects on cognitive functions and
memory were detected. In fact, there was a trend toward improvement in memory and
other cognitive functions after ECT in both groups, with no significant
difference between them. The two stimulus waveforms studied (brief and ultrabrief
pulse) thus appear to be equally effective and free of deleterious effects on
memory and cognition. The response in schizophrenic patients was remarkable and
deserving of further study.
PMID- 9641803
TI - Attenuation of ECS-induced retrograde amnesia by using an herbal formulation.
AB - Earlier research indicated the efficacy of a complex herbal formulation in the
attenuation of electroconvulsive shock (ECS)-induced amnestic deficits in rats;
this study sought to ascertain whether a simplified herbal formulation (Memorin;
Phyto-Pharma, India) also was effective. Rats pretreated for a fortnight with
Memorin (200 mg/kg/day) or vehicle were exposed to a passive-avoidance learning
paradigm in a shuttle box. The next day, the rats were administered two true or
sham ECSs, 5 h apart; recall of the pre-ECS learning was reassessed on the
following day. ECS was found to produce significant retrograde amnesia (p <
0.002). Memorin attenuated the ECS-induced amnesia (p = 0.00003) without
influencing the ECS seizure duration. The clinical implications of these findings
are discussed.
PMID- 9641804
TI - Anesthetic induction for ECT with etomidate is associated with longer seizure
duration than thiopentone.
AB - Many factors influence seizure duration associated with electroconvulsive therapy
(ECT). This is a chart review study to assess seizure duration measured with both
electroencephalography and electromyography after anesthetic induction with
either thiopentone or etomidate. Thirty-seven patients receiving ECT for
depression were entered into the study, and a pair of seizures was measured from
each patient. Alternate induction agents were used in sequential pairings, and
the study was controlled for interval between seizures, laterality, and percent
energy. Etomidate was associated with a significantly (p = 0.0002, F = 15.84, df
= 1, analysis of variance) longer seizure duration (mean = 34.43 s, SD = 16.06)
than thiopentone (mean = 21.73 s, SD = 9.33).
PMID- 9641805
TI - Acute post-ECT cardiovascular response: a comparison of threshold right
unilateral and bilateral ECT.
AB - The effect of electrode placement on cardiovascular responses was studied. Rate
pressure product and diastolic blood pressure before anesthesia and 30 s after
electroconvulsive therapy (ECT) seizure were recorded. Recordings were made at
the first (threshold ECT) session in 124 bilateral ECT (BLECT) and 95 unilateral
ECT (ULECT) consenting patients. Postictal rate pressure product (RPP) was
significantly higher after BLECT than ULECT. Mean increase in RPP from pre- to
postictal phase was 31% in the former. The corresponding change with ULECT (20%)
was significantly smaller. In the stepwise, multiple regression model, pre-ECT
RPP, age, and stimulus laterality significantly contributed to postictal RPP. No
cardiovascular complications occurred in any of the 219 ECT sessions.
PMID- 9641806
TI - Propofol anesthesia, seizure duration, and ECT: a case report and literature
review.
AB - Propofol is a nonbarbiturate anesthetic induction agent known to have anti
convulsant properties. When used as an anesthetic for electroconvulsive therapy
(ECT), it can reduce seizure duration to a significant degree, which may not be
fully appreciated. A case is presented in which propofol caused a 63.1% reduction
in mean seizure duration compared with preceding and subsequent treatments with
thiopental anesthesia. The literature on the use of propofol for ECT was reviewed
with specific reference to its effect on seizure duration and any evidence of
superiority to the barbiturate induction agents. It is concluded that propofol
may have only very circumscribed indications as an anesthetic for ECT. If used,
psychiatrists and anesthetists must be aware of its potency as an anticonvulsant.
PMID- 9641807
TI - Ventricular tachycardia with ECT.
AB - A case is presented in which a patient with ischemic heart disease developed
episodic, nonsustained ventricular tachycardia (VT) during electroconvulsive
therapy for major depression. The VT had a frequency of 200 beats/min and ceased
spontaneously after 17 s. Altered autonomic discharge in the presence of ischemia
is the probable cause. Predisposing factors, as well as management
considerations, are discussed.
PMID- 9641808
TI - Electroconvulsive therapy in patients with long bone fractures.
AB - Two elderly patients with severe depression were treated with electroconvulsive
therapy despite long bone fractures. Good liaison was maintained throughout with
the orthopaedic surgeons and anaesthetists. Both of the patients improved
significantly, and there were no musculoskeletal complications.
PMID- 9641809
TI - Duration of liquid fast before ECT.
PMID- 9641810
TI - Prolonged seizures in the young.
PMID- 9641811
TI - ECT in the presence of a cerebral aneurysm.
PMID- 9641812
TI - ECT with implantable cardioverter defibrillator.
PMID- 9641813
TI - Junior doctors' training in the theory and the practice of electroconvulsive
therapy.
AB - Recent advances in knowledge about effective administration of electroconvulsive
therapy (ECT) has placed great emphasis on the importance of good training and
supervision of those administering it. The American Psychiatric Association
requires that doctors be specifically accredited before they are allowed to give
ECT. In England and Wales training is much more informal and ECT is often given
by junior doctors. Doctors rostered to administer ECT in Wales and in two areas
of England were surveyed as part of the College's third audit of ECT. About two
thirds of respondents were at senior house officer level. The training in ECT
appeared of variable quality and one-half had not been supervised by an
experienced psychiatrist on the first occasion they administered ECT. Responses
to exam-type questions revealed that 45% lacked knowledge about one or more basic
issue related to effective administration of ECT.
PMID- 9641814
TI - [Significance of ICH--toxicokinetics guidance and its practice--a useful approach
for safety drug development].
AB - In the International Conference on Harmonization (ICH), "Note for Guidance on
Toxicokinetics: the Assessment of Systemic Exposure in Toxicity Studies (ICH
Harmonized Tripartite Guideline)" was signed off in October 1994 by 6 parties of
Japan, EU and the United States. The Ministry of Health and Welfare, Japan, has
issued the notification "Upon the Guidance for Toxicokinetics (Assessment of
Systemic Exposure in Toxicity Studies)" (Yakushin No. 443 dated July 2, 1996).
The notification stated that pivotal toxicity study which initiates on and after
January 1st, 1997 should includes appropriate Toxicokinetic study. In the ICH
Guidance for pharmaceuticals, TK is defined as the generation of pharmacokinetic
data, either as an integral component in the conduct of non-clinical toxicity
studies or in specially designed supportive studies, in order to assess systemic
exposure. These data may be used in the interpretation of toxicology findings and
their relevance to clinical safety issues. TK study is considered to be
indispensable for safety assessment, and thus should be conducted in compliance
with the GLP regulations. The ICH guidance also emphasizes that the exposure
assessment in individual toxicity studies should be based on a flexible and step
by step and a case by case decision making process. In this review article, the
background for the introduction of this TK Guidance, the outline of the ICH-TK
Guidance, the definition and fundamental principles of the ICH-TK, and its
toxicological significance and practical problems in the conduct of TK study are
described.
PMID- 9641815
TI - [Building information infrastructure at research institutions that support health
hazard control].
AB - In recent years the Ministry of Health and Welfare (MHW) encountered large scale
health hazards and medicare incidents that required flexible, intersectional, and
dynamic responses. Both research institutions under the MHW and their researchers
got involved in project teams which were organized in order to cope these hazards
and incidents. However it might be more effective if some information
infrastructure for hazard control is built as one component of the MHW hazard
management system. In this paper the design concept and implementation for such
information infrastructure were discussed. The infrastructure consists of
computer networks and systems which are based on the Internet and the related
technologies such as WWW.
PMID- 9641816
TI - [Modulations of human growth hormone receptor level on the cell surface].
AB - Using a monoclonal antibody (GHRP2-88) raised against the extracellular portion
of human growth hormone receptor (hGHR), the mechanisms on modulations of
cellular levels of hGHR were investigated in human IM-9 cells. Upon stimulation
with human growth hormone (hGH), hGHRs on the cell surface are down-regulated
through internalization and degradation of hGHR. For hGHR internalization, hGH
mediated dimerization of hGHRs, but not staurosporine-sensitive phosphorylation
is required. For hGHR degradation, however, staurosporine-sensitive
phosphorylation is necessary. In the absence of hGH, hGHRs on the cell surface
are cleaved to release human growth hormone-binding proteins (hGH-BPs), probably
by a metalloprotease. In the presence of hGH, the hGH-BP release was rather
decreased based on the reduction in cell surface hGHRs. Thus, the cell surface
level of hGHR may be regulated post-translationally by the two mechanisms
depending on the external hGH levels.
PMID- 9641817
TI - [Study of N-nitroso compounds which have NO-release ability].
AB - Nitric oxide (NO), which plays an important role in the vital functions of
organisms, is gaseous and labile molecule. Much attention has been paid to the
stability and easily handling of NO donors, for careful handling of NO is
required during experimental work. We synthesized a series of aromatic N
nitrosoureas and N-nitrosamides which efficiently liberates NO at room
temperature. Generation of NO from the aromatic N-nitroso compounds was
chemically confirmed by the trapping of NO as a nitrosyl complex of
tetraphenylporphyrinatocobalt (II) and spectrophotometrically quantified by means
of the Griess reaction using a newly designed test apparatus. 3,3-Dibenzyl-1-(4
tolyl)-1-nitrosourea showed the greatest NO-generating ability among the
synthesized N-nitroso compounds. Further, the NO-generating ability was related
to the reciprocal of the ID50 value for growth inhibition of cultured L-5178Y
cell by the aromatic N-nitroso compounds.
PMID- 9641818
TI - [Purinoceptor-induced cytoplasmic calcium oscillation in megakaryocytes].
AB - Megakaryocytes isolated from rat bone marrow respond to externally applied ATP
and ADP, showing a periodic K+ current that reflects oscillation in cytoplasmic
calcium concentration. The agonist selectivity of the purinoceptor on the
megakaryocyte is unique. In addition, the intracellular mechanism of calcium
oscillation and the effects of many modulating factors were investigated.
PMID- 9641819
TI - [Oxidation and reduction of nitroarene as environmental mutagens].
AB - Newly synthesized dinitrobenzo[a]pyrenes and 6-aza analogues of 1- and 3
nitrobenzo[a]pyrenes showed strong mutagenic activity in Salmonella assays (TA98
and TA98NR). Nitroreduction is essential for metabolic activation of nitroarene.
The structure activity relationships of mono-, di- and trinitrophenanthrene were
studied. Electrochemical ease of nitroreduction and dihedral angles of nitro
substituents to aromatic rings is found to be important factor to determine their
mutagenic potency. Nitroarene is oxidatively metabolized to form hydroxylated and
nitrosubstituted derivatives and the same oxidative products were obtained by the
reaction of nitroarene with chemically generated superoxide anion radical,
suggesting the participation of superoxide in metabolic oxidation of nitroarene.
Catalytic activity of nitroarene as a mediator in the reductive activation of
molecular oxygen was also evaluated by using potential step chronocoulometry
method. The potential relevence of toxicity caused by redox cycling could be
solved by using this method.
PMID- 9641820
TI - [Studies on the stability of 89 pesticides in organic solvent].
AB - The stability of 89 pesticides (17 organochlorine, 33 organophosphorus, 8
pyrethroid, 12 carbamate, and 19 other pesticides) in 6 kinds of organic solvents
(methanol, ethanol, 2-propanol, ethyl acetate, n-hexane, and acetone) was
investigated using gas chromatography/mass spectrometry (GC/MS). All of the
investigated pesticides were stable in all of the tested organic solvents during
storage for 6 hours at room temperature in the dark except captafol, captan,
phosmet, chinomethionat, and dicofol. However, the decreases of captafol, captan,
phosmet, and chinomethionat were observed in methanol. The decreases of captafol,
captan, and phosmet were also observed in ethanol. Moreover, the decrease of
dicofol was observed in acetone. The decrease of captafol dissolved in methanol
at a concentration of 2 micrograms/ml was faster than those of captan, phosmet,
and chinomethionat; the residual captafol was 75% after 30 min of storage.
Dicofol dissolved in acetone also decreased during storage in a refrigerator.
4,4'-dichlorobenzophenone (DCBP) and chlorobutanol were detected in the acetone
solution of dicofol after storage. Furthermore, it was found that dicofol was
decomposed by acetone at an injection port, and DCBP and chlorobutanol were
formed when it was injected into GC with acetone.
PMID- 9641821
TI - [A 13-week subchronic oral toxicity study of carob germ colour in F344 rats].
AB - A13-week subchronic oral toxicity study of carob germ colour, one of natural
colour additives was carried out in F344 rats at dose levels of 5.0, 1.7, 0.6,
0.2 and 0% in the powdered diet. Rats were randomly allocated to 5 groups, each
consisting of 10 males and 10 females. No animals died during the experiment and
no changes in body weights and food intakes were observed in any dosed groups.
Changes indicating obvious toxicity of carob germ colour were not observed in the
organ weights, hematological, serum biochemical and histopathological
examinations. These findings indicate that the treatment of 5% carob germ colour
in diet for 13 weeks did not cause any significant toxicity in rat.
PMID- 9641823
TI - [Effects of 16-week dietary administration of 2-amino-3,8-dimethylimidazo[4, 5
f]quinoxaline in rats].
AB - 2-Amino-3,8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx), a heterocyclic amine
found in cooked meats, is carcinogenic in mice and rats at high doses. In order
to examine the toxicity including preneoplastic changes at the lower doses, a
total of 170 male Fischer 344 rats were administered MeIQx for 16 weeks at a dose
of 100, 10, 1, 0.1, 0.01, 0.001 ppm or 0 ppm in the diet. The numbers of GST-P
positive foci and BrdU-labeling indices in the liver were significantly increased
by the dietary administration of 10 ppm and 1 ppm or more of MeIQx respectively,
when compared with the basal diet-fed control rats. Aberrant cry p tfoci (ACF)
were also significantly increased in the 100 ppm MeIQx group as compared to the
control value. No histopathological changes indicating obvious toxicity of MeIQx
were observed in the major organs other than the liver and large intestine. In
conclusion, our results clearly indicate that MeIQx selectively targets the liver
and large intestine of rats as organs for the toxicity, but dose not affect the
other major organs at low doses.
PMID- 9641822
TI - [13-week subchronic oral toxicity study of phaffia colour in F344 rats].
AB - A 13-week subchronic oral toxicity study of phaffia colour was performed in both
sexes of F344 rats by feeding of CRF-1 powder diet containing 0, 0.2, 0.6, 1.7
and 5%. Rats were randomly divided into 5 groups, each consisting of 10 males and
10 females. No animals died during the administration period. There were no
treatment-related changes in body weight gain, hematological and blood
biochemical examination. No treatment-related histopathological changes were also
observed in any dosed groups. These findings indicate that the treatment of 5%
phaffia colour in diet for 13 weeks does not cause any toxicological changes in
rats.
PMID- 9641824
TI - [Effects of dietary magnesium deficiency in the rat: with special reference to
ultrastructural examination].
AB - Epidemiologically, it has been suggested that dietary magnesium/calcium imbalance
is associated with the risk of heart diseases. In the present study, the effects
of magnesium deficiency and/or calcium over intake were investigated in rats.
Male Sprague-Dawley rats were divided into 4 groups, and respectively fed basal
diet (AIN-76) alone (Group 1), calcium-doubled AIN-76 diet (Group 2), magnesium
deficient AIN -76 diet (Group 3) and magnesium-deficient/calcium-doubled AIN-76
diet (Group 4) for 19 days. A biochemical assay using inductively coupled plasma
showed that the magnesium concentrations of the femoral bone and serum were
significantly (p < 0.001) lower in Groups 3 and 4 than in Group 1. The lipid
peroxides of the heart in Group 4 and of the liver in Groups 3 and 4 were
increased as compared to the Group 1 values although there was no statistical
significance. Ultrastructurally, degenerative changes of organellas including
mitochondria were observed in myocardial, liver and renal tubule cells of Groups
2-4. Severe degeneration such as disorganization, lysis and disarrangement of
myofibrils was most evident in myocardial cells of Group 4. Our results thus
suggest that dietary magnesium deficiency gives rise to retrogressive changes in
some organs including the heart, and concurrent calcium overintake
synergistically enhances the myocardial injury due to magnesium deficiency.
PMID- 9641825
TI - [A 13-week subacute oral toxicity study of pectin digests in rats].
AB - A 13-week subacute oral toxicity study of pectin digests was performed in both
sexes of F344 rats. Water containing 0, 0.15, 0.5, 1.5 or 5% pectin digests was
fed to 10 males and 10 females per group to detect its toxicity. No animals died
during the administration period. Body weight gain was suppressed in male of the
5% group compared with the 0% group. Serum biochemistry analysis revealed a
significant increase in BUN in male group treated with 5% and increases in CRN in
male group treated with 1.5% or more. The weight of liver was significantly
increased in female groups treated with 1.5% or more. Histopathologically, no
treatment-related damage was observed in any dosed groups. Based on these
results, the NOEL of pectin digests for both sexes in F344 rats was considered to
be 0.5% in drinking water (male 545, female 657 mg/kg/day).
PMID- 9641826
TI - [Stereochemical structure of d-borneol in "the Japanese Standards of Food
Additives"].
AB - d-Borneol is shown at "The Japanese Standards of Food Additives" the sixth
edition. Though the absolute stereochemistry of this compound is described as 1S,
2R-form, the opposite optical rotation for the same structure is described in
other literatures. The application of improved Mosher's method to d-borneol
resulted in 1R, 2S-form for its absolute stereochemistry.
PMID- 9641827
TI - [Cytotoxicity of chemicals used in household products: estimation of eye
irritating potency of 25 chemicals tested during 1991-1996].
AB - Cytotoxicity potential of chemicals was evaluated by determining the
concentrations inducing 50% reduction of neutral red (NR) uptake into Chinese
hamster fibroblast V79 cells compared with control culture (IC50). The results of
cytotoxicity test for surfactants with the data produced by the in vivo Draize
eye and skin irritation test were compared. There was a good correlation between
cytotoxicity and eye irritation score obtained from the Draize test. In contrast,
no correlation was observed between Draize skin irritation score and cytotoxic
potential of chemicals. Therefore, the NR cytotoxicity test was regarded as a
possible in vitro model for predicting eye irritation. Based on the IC50 values
in the NR cytotoxicity test, the eye irritation classification (weak, moderate
and strong) for each chemical used in household products has been established. We
evaluated the cytotoxicity of 25 chemicals used for antimicrobial, rubber
accelerator, rubber antioxidant, ultraviolet absorber etc. in household products,
and estimated the eye irritating potency of these test chemicals according to the
criterion.
PMID- 9641828
TI - [Specific determination of deltamethrin and tralomethrin by preparative HPLC and
GC-ECD].
AB - Tralomethrin quickly changes to deltamethrin in gas chromatograph by
debromination. Therefore deltamethrin and tralomethrin are not able to be
distinguished by gas chromatographic determination. A method for specific
determination of deltamethrin and tralomethrin was established. The method
consists of fractionation by high performance liquid chromatography and
determination by gas chromatography. Recoveries of deltamethrin and tralomethrin
spiked to three agricultural products were from 42 to 78% and from 18 to 76%,
respectively with relative standard deviations ranging from 0.3 to 15%. From the
analysis of samples spiked with tralomethrin, it was found that a part of
tralomethrin quickly changed to deltamethrin in homogenate of agricultural
products. The addition of phosphoric acid to the homogenate did not prevent the
change of tralomethrin.
PMID- 9641829
TI - [Analysis of B-3 desamido insulin in human insulin preparations by HPLC].
AB - The content of A-21 desamido insulin (A-21 DI) and B-3 desamido insulin (B-3 DI)
in human insulin preparations was measured by new RP-HPLC method using a neutral
eluent (pH 6.5). Sometimes the content of B-3 DI in human insulin preparations
was about two times larger than that of A-21 DI. In particular, in the case of
neutral insulin injection, the content of B-3 DI has increased remarkably as the
increase of total desamido content. The content of B-3 DI obtained by the new RP
HPLC method will open the new aspect of the impurity test for insulin
preparations.
PMID- 9641830
TI - [Application of thermogravimetry to loss on drying test and water-content
determination of drugs].
AB - Thermogravimetry, one of the techniques of thermal analysis, was applied to the
quality control of drug raw materials as a "Loss on Drying" or for "Water Content
Determination". Twenty two kinds of drugs were selected for the comparison of the
applicability of thermogravimetry with that of Loss on Drying Test and/or Water
Content Determination by the Karl-Fisher method. In all kinds of drugs, it was
ascertained that the results with thermogravimetry agreed well with those
obtained by Loss on Drying test and/or Karl-Fisher method. In conclusion,
thermogravimetry can be used as a substitute for the Loss on Drying test in cases
where drug possess a water bound strongly. Further, thermogravimetry can be
utilized for some drugs to which the Karl-Fisher method cannot be applied due to
their insolubility in Karl-Fisher reagents.
PMID- 9641831
TI - [Studies on the bottles of mineral water and the foreign plastic like
substances].
AB - The containers of mineral water and the foreign plastic substances which were
found in the mineral water were investigated. Most of plastic bottles were made
of polyethylene terephthalate (PET) and the caps were made of polypropylene (PP),
polyethylene (PE) or aluminum. PE liners were attached to some caps. Most of the
foreign plastic substances were PET while others were PE, PP, Teflon and rubber.
Some bottles had a scratch on the top inside. The origin of most PET fragments
was presumed to be scraped off the bottles by the lowering of the injection
nozzle during the water filling process. The sources of the other substances were
also determined.
PMID- 9641832
TI - [Preliminary screening for antiviral AIDS drugs. VIII. Report for fiscal year
1995].
AB - Preliminary screening of antiviral AIDS drugs has been carried out using three
different in vitro assay systems. Among 96 samples of different origin tested,
two were shown to inhibit the growth of HIV in vitro. One of the positive samples
(plant origin) has hopeful signs, as the ranges of effective doses are wider than
those of most of positive samples which had been found by us.
PMID- 9641833
TI - [Development of a geographical information system and its application to
Escherichia coli O-157 patient distribution].
AB - The so called Geographical Information System (GIS) is one of the basic tools for
wide range of public health applications. We had developed a general purpose GIS
and applied it to represent geographical distribution of patients of the
bacterium E. coli O-157 which bursted out in Japan last early summer particularly
at Sakai City in Osaka Prefecture. The patient record have been supplied from the
Food Safety Office of the Ministry of Health and Welfare. These records were
handled by EXCEL. The basic geographical data was constructed from the map data
provided by Japan Geographical Survey Institute, and ArcView 2 was used as the
map system. The maps were converted to Graphics Interchange Format (GIF) files
and put on our Web server.
PMID- 9641834
TI - [Dissemination of the Japanese version of the International Chemical Safety Card
(ICSC) on the World Wide Web (WWW)].
AB - ge of the Japanese version of the International Chemical Safety Cards (ICSC). We
prepared the Japanese text files of ICSC, converted them into HTML files and also
prepared the dictionary database for the retrieval system, using programs which
we developed. These programs shortened the time of work remarkably. 2D- and 3D
structures of chemicals were also incorporated in each ICSC page. Approximately
900 ICSCs in Japanese are provided at the moment on the homepage.
PMID- 9641835
TI - [First drafts of the Environmental Health Criteria (EHC) circulated for comments
by IPCS in 1996.4-1997.3].
PMID- 9641836
TI - [Estimated production by the official inspection of coal-tar dyes (including dye
aluminum lakes) in 1996].
AB - The number of official inspection of coal-tar dyes and their lakes from April in
1996 till March in 1997 were 581 in total. The quantity which passed inspection
amounted to 164.5 ton in Japan. The production of color in each month was
summarised in Table1, and by each producing company in Table2. The food coal-tar
dye produced in the largest quantity was Food Yellow No. 4, occupying 43.4% in
this period.
PMID- 9641837
TI - [Determination and survey of starting materials, intermediates, and subsidiary
colors in food color of azo dye by high performance liquid chromatography].
AB - A method for determination of starting materials, intermediates and subsidiary
colors in food color of azo dye was developed by use of HPLC. The following
conditions were used for analysis: column, L-column ODS (4.6 mm phi x 250 mmL);
mobile phase, 0.02 M ammonium acetate (A), acetonitrile (B); concentration
gradient, perform the linear concentration gradient from A:B (100:0) to (60:40)
for 40 min; detection, starting materials and intermediates at 239 nm, and
subsidiary colors at 510 nm. Standard material, domestic product and imported
product were analyzed by the present HPLC method and impurities were measured.
Recoveries of each impurity from azo dye averaged 99.1-103.5%. The detection
limit was 0.05 microgram/g for each impurity.
PMID- 9641838
TI - [Epinephrine Bitartrate Reference Standard (Control 951) of National Institute of
Health Sciences].
AB - The raw material for epinephrine bitartrate was tested for preparation of the
"Epinephrine Bitartrate Reference Standard (Control 951)" of National Institute
of Health Sciences. Analytical data obtained were as follows: melting point,
148.6 degrees C (decomposition); UV spectrum, lambda max = 279 nm; IR spectrum,
the same as that of JP Epinephrine Bitartrate Reference Standard (Control 792);
optical rotation, [alpha]20D = -52.8 degrees; thin-layer chromatography, one
impurity was detected; high-performance liquid chromatography, no impurity was
detected; loss on drying, 0.01%; assay, 99.6% by potentiometric titration, 100.3%
by spectrophotometry. Based on the above results, the raw material was authorized
as the Epinephrine Bitartrate Reference Standard (Control 951) of National
Institute of Health Sciences (Japanese Pharmacopoeia).
PMID- 9641839
TI - [Riboflavin Reference Standard (Control 951) of National Institute of Health
Sciences].
AB - The raw material for riboflavin was tested for preparation of the "Riboflavin
Reference Standard (Control 951)" of National Institute of Health Sciences.
Analytical data obtained were as follows: melting point, 284.6 degrees C
(decomposition): specific absorbance, E1cm1% = 857 (267 nm), 277 (373 nm), 326
(445 nm); IR spectrum, the same as that of JP Riboflavin Reference Standard
(Control 921); optical rotation, [alpha]20D = -135.6 degrees; thin-layer
chromatography, three impurities were detected; high-performance liquid
chromatography, a small amount of 10 impurities were detected: loss on drying,
0.10%; assay, 100.4% by spectrophotometry. Based on the above results, the raw
material was authorized as the Riboflavin Reference Standard (Control 951) of
National Institute of Health Sciences (Japanese Pharmacopoeia).
PMID- 9641840
TI - [Estradiol Reference Standard (Control 961) of National Institute of Health
Sciences].
AB - The raw material for estradiol was examined for preparation of the "Estradiol
Reference Standard (Control 961)" of National Institute of Health Sciences.
Analytical data obtained were as follows: melting point, 179.1 degrees C; UV
spectrum, lambda max = 281 nm; IR spectrum, the same as that of the Estradiol
Reference Standard of National Institute of Health Sciences (Control 931);
optical rotation, [alpha]20D = +79.5 degrees; thin-layer chromatography, one
impurity was detected; high-performance liquid chromatography (HPLC), a trace
amount of three impurities were detected; loss on drying, 3.17%; assay, 99.4% by
UV spectrophotometry and 99.0% by HPLC. Based on the above results, the raw
material was authorized as the Estradiol Reference Standard (Control 961) of
National Institute of Health Sciences.
PMID- 9641841
TI - [dl-Camphor Reference Standard (Control 961) of National Institute of Health
Sciences].
AB - The raw material of dl-camphor was examined for the preparation of the "dl
Camphor Reference Standard (Control 961)" of National Institute of Health
Sciences. Analytical data obtained are as follows: UV spectrum, lambda max = 290
nm; IR spectrum, the same as that of the present JP Camphor Reference Standard
(Control 953); melting point, 179.1 degrees C; purity test by gas-chromatography
(GC), three kinds of impurities were detected; assay by GC, 99.8%. Based on the
above results, the candidate raw material was authorized as the dl-Camphor
Reference standard (Control 961) National Institute of Health Sciences (Japanese
Pharmacopoeia).
PMID- 9641842
TI - [Chlormadinone Acetate Reference Standard (Control 961) of National Institute of
Health Sciences].
AB - The raw material for chlormadinone acetate was tested for preparation of the
"Chlormadinone Acetate Reference Standard (Control 961)" of National Institute of
Health Sciences. Analytical data obtained were as follows: melting point, 215. 3
degrees C; UV spectrum, lambda max = 283.5 nm; IR spectrum, the same as that of
JP Chlormadinone Acetate Reference Standard (Control 885); optical rotation,
[alpha]20D = -13.0 degrees; thin-layer chromatography, one impurity was detected;
high-performance liquid chromatography, two impurities were detected; loss on
drying, 0.01%; assay, 99.4% by spectrophotometry and 99.5% by HPLC. Based on the
above results, the raw material was authorized as the Chlormadinone Acetate
Reference Standard (Control 961) of National Institute of Health Sciences
(Japanese Pharmacopoeia).
PMID- 9641843
TI - [Hydrocortisone Acetate Reference Standard (Control 961) of National Institute of
Health Sciences].
AB - The raw material of hydrocortisone acetate was tested for the preparation of the
"Hydrocortisone Acetate Reference Standard (Control 961)". Analytical data
obtained were as follows: IR spectrum, specific absorption wave numbers at 3428,
1748, 1723, 1631, and 1375 cm-1; specific absorbance, E1cm1% (242 nm) = 406; thin
layer chromatography, no impurities were detected until 0.05 microgram; high
performance liquid chromatography (HPLC), 2-3 impurities were detected and the
amount of the total impurities was estimated to be about 0.2%; assay by HPLC,
100.7%. Based on the above results, the raw material was authorized as the
Japanese Pharmacopoeia Reference Standard (Control 961).
PMID- 9641844
TI - [Ulinastatin Reference Standard (Control 971) of the National Institute of Health
Sciences].
AB - The "Ulinastatin Reference Standard (control 971)" of National Institute of
Health Sciences was prepared. The standard material was evaluated in
collaboration with one domestic laboratory, and the potency of trypsin inhibiting
activity was determined to be 3, 100 units/vial by relative assay method against
the Ulinastatin Reference Standard (control 942). Other analytical data obtained
were as follows: UV maximum absorption was observed at 277 nm, and the molecular
weight was estimated to be about 66,300 by gel filtration method. Maximum
variance of material contents in 10 vials was 2.29%. Based on the above results,
this standard material was authorized to be the "Ulinastatin Reference Standard
(control 971)" of the National Institute of Health Sciences.
PMID- 9641845
TI - [The Endotoxin Reference Standard of the National Institute of Health Sciences
(the Japanese Pharmacopoeia Endotoxin Reference Standard) (Control 971)].
AB - The third lot (Control 971) of the Endotoxin Reference Standard of the National
Institute of Health Sciences (the Japanese Pharmacopoeia Endotoxin Reference
Standard) was prepared. The potency of the new lot was assayed against USP
Endotoxin Reference Standard (EC-6) and defined as containing 13,000 endotoxin
units (EU) per vial by a collaborative study of 7 laboratories.
PMID- 9641846
TI - [Exceptional Application of Content Uniformity Test and Weight Variation Test in
the Japanese Pharmacopoeia 13 revision and usage of these tests for in-process
tests].
AB - The criteria of Content Uniformity test and Weight Variation test in JP 13 were
greatly changed to reduce consumer's risk. The new criteria were set to keep the
rate of defectives in lots passing the tests less than the acceptable rate.
However, in some cases, the new criteria can not directly be applied to some
formulations and several modifications are needed in the criteria. In this
report, the several resolution of this problem are represented. The applicability
of these tests for in-process tests is also discussed.
PMID- 9641847
TI - [A method for knowing the statistical reliability of instrumental measurements].
AB - The precision of instrumental measurements, usually expressed by SD (standard
deviation) or RSD (relative standard deviation) is of importance in a society as
well as in a world of analytical chemistry. For example, the detection limit and
confidence intervals of calibration lines which are based on the precision are
inevitable for regulatory science. As is well-known in statistics, however, a
small number of repetitive experiments (e.g., 5) lead to a poor reliability of
the precision. This presentation shows a method (called FUMI theory) which can
provide a precision from a single measurement of noise and signal without any
repetitive measurements. The statistical reliability of the precision from the
FUMI theory corresponds to that from the repetitive method of 50 experiments.
PMID- 9641848
TI - [Relationship between design of calibration and precision of measurement].
AB - The method to estimate the confidence interval of calibration line was
established. The method used the variance of measurement that can be predicted
based on the background fluctuation. The validity of the estimated confidence
interval was verified experimentally. The relationship between the calibration
design and the analytical precision can be predicted with this method. The ill
designed calibration line deteriorates the trueness of the measurement as well as
the precision.
PMID- 9641849
TI - [A proposal by the Japanese Pharmacopoeia for a method to set an endotoxin limit
for parenteral drugs to be tested].
AB - The Bacterial Endotoxins Test has been extensively revised in the JP 13. In
addition to the limit test with gelation, adopted in the JP 12, quantitative
methods using gel-clot, turbidimetric and chromogenic techniques have been
adopted in the JP 13. As for the endotoxin limit for monographs, it was specified
for Water for Injection alone in the JP 12. Since the issue of the JP 13
Supplement is under consideration, the possibility of replacing the Pyrogen Test
(which is required for some main products in the current JP 13 monographs) with
the Bacterial Endotoxins Test is now being discussed. For international
harmonization of the Bacterial Endotoxins Test, it seems to be preferable to
follow (if acceptable) the FDA method that was established in 1987 to set an
endotoxin limit for products intended for parenteral use. This would then be
followed by both the USP and EP. Thereby a draft for the Method to set the
Endotoxin Limit, which is to be described in the Information chapter of the JP 13
Supplement, is being prepared. This report details an explanation of the draft,
the definition of the endotoxin unit (EU) and its defined process, and the
compliance with the replacement of the Pyrogen Test by the Bacterial Endotoxins
Test, etc.
PMID- 9641850
TI - [Studies on the molecular weight standards for size-exclusion chromatography-
standardization of a molecular weight standard for water-soluble polymers].
AB - The possibility of the standardization of molecular weight standards for size
exclusion chromatography (SEC) was investigated in the case of water-soluble
polysaccharides such as dextran, hyaluronate and chitosan. In the case of
dextran, comparing the method adopted for dextran in EP and BP, it was shown that
pullulan, one of commercially available molecular weight standards, can be used
in usual SEC method. For hyaluronate and chitosan, applying the Mark-Houwink
correction to the calibration curve obtained by pullulan, the acceptable
molecular weights could be estimated.
PMID- 9641851
TI - Craniofacial electromyogram activation response: another indicator of anesthetic
depth.
AB - OBJECTIVE: After finding that craniofacial EMG preceding a stimulus was a poor
predictor of movement response to that stimulus, we evaluated an alternative
relation between EMG and movement: the difference in anesthetic depth between the
endpoint of EMG responsiveness to a stimulus and endpoint of movement
responsiveness to that stimulus. We expressed this relation as the increment of
isoflurane between the two endpoints. METHODS: We measured EMG over the frontalis
muscle, over the corrugator muscle, and between the Fp2 and the mastoid process
as patients emerged from general anesthesia during suture closing of the surgical
incision. Anesthesia was decreased by controlled washout of isoflurane while
maintaining 70% N2O, and brain isoflurane concentrations ((C)isoBrain) were
calculated. We studied a control group of 10 patients who received only surgical
stimulation, and 30 experimental patients who intermittently received test
stimuli in addition to the surgical stimulation. Patients were observed for
movement responses and EMG records were evaluated for EMG activation responses.
We defined an EMG activation response to be a rapid voltage increase of at least
1.0 microV RMS above baseline, with a duration of at least 30 s, in at least one
of the three EMG channels. Patient responses to stimuli were classified as either
an EMG activation response without a move response (EMG+), a move response
without an EMG activation response (MV+), both an EMG activation response and a
move response (EMG+MV+), or no response. We defined the EMG+ endpoint to be the
threshold between EMG+ response and nonresponse to a stimulus, and estimated
(C)isoBrain at this endpoint. We similarly defined the move endpoint and
estimated the move endpoint (C)isoBrain. We then calculated the increment of
(C)isoBrain at the EMG+ endpoint relative to the move endpoint. MAIN RESULTS: For
the 30 experimental patients, the initial response to a test stimulus was an EMG+
in 14 patients (47%), an EMG+MV+ in 12 patients (40%), and a MV+ in 1 patient
(3%); no response occurred by the time surgery was completed in 3 patients (10%).
No response occurred in 7 of the control patients (70%). Of the 14 patients with
an initial EMG+ response to a test stimulus, 9 patients later had a move
response. For these 9 patients, the increment of (C)isoBrain between the EMG+
endpoint and move endpoint was 0.11 +/- 0.04 vol%, (mean +/- SD). CONCLUSIONS:
Our results suggest that, given the circumstances of our study, an EMG activation
response by a nonmoving patient indicates that the patient is at an anesthetic
level close to that at which movement could occur. However, because the first EMG
activation response may occur simultaneously with movement, the EMG activation
response cannot be relied upon to always herald a move response before it occurs.
Our results also suggest that EMG responsiveness to a test stimulus may be used
to estimate the anesthetic depth of an individual patient.
PMID- 9641853
TI - Clinical evaluation of tracheal pressure estimation from the endotracheal tube
cuff pressure.
AB - OBJECTIVE: Air flow through an endotracheal tube causes a pressure drop across
the tube. This pressure drop creates a difference between air pressure measured
in the trachea and the pressure measured in the breathing circuit, which can lead
to errors when calculating pulmonary mechanics and when setting ventilators. We
have developed a method of estimating tracheal pressure from the pressure in the
endotracheal tube cuff and tested this system in clinical trials. METHODS:
Pressure measurement ports were placed between the Y piece of the ventilator
circuit and the ETT connector, in the trachea at the carinal end of the ETT, and
in the ETT cuff inflation line. Tracheal pressures and cuff pressures were found
at end-inspiration and end-expiration (no flow states) and used to define a
linear relationship between cuff pressure and tracheal pressure. Using the
estimated tracheal pressure (Ptrach) and the measured pressure at the Y piece of
the breathing circuit (PY), the pressure drop across the ETT was found as a
function of flow through the tube. Tracheal pressure was then calculated from the
flow-dependent pressure drop and PY. Tests of this system were performed in six
patients in the operating room and six patients in the intensive care unit.
RESULTS: The flow-based tracheal pressure estimates were within 0.7 +/- 0.4 cm
H2O of actual tracheal pressure (mean +/- SD). At peak inspiratory pressure the
difference averaged 0.5 +/- 0.3 cm H2O. The difference between our estimate of
tracheal pressure and actual tracheal pressure was always less than 1 cm H2O.
CONCLUSION: The flow-based tracheal pressure estimates were accurate during
intermittent spontaneous breathing, but not during spontaneous breathing or with
a poorly inflated cuff. The estimates were more immune to noise than the cuff
based estimates of tracheal pressure. The estimates of tracheal pressure measured
from the ETT cuff should be accurate enough for clinical use in the operating
room.
PMID- 9641852
TI - New equipment for neuromuscular transmission monitoring: a comparison of the TOF
Guard with the Myograph 2000.
AB - OBJECTIVE: The present study is to clarify whether the bias and limits of
agreement of the TOF-Guard and the mechanomyograph differ from those of two
mechanomyographs on contra lateral arms. Previous studies of the bias and limits
of agreement between acceleromyographical (TOF-Guard) and mechanomyographical
measurements of neuromuscular transmission did not take the error introduced by
using contra lateral arms into consideration. METHODS: Fifty-two women undergoing
gynecological surgery were anesthetized with midazolam, fentanyl, thiopental,
halothane and nitrous oxide. Neuromuscular blockade was induced and maintained
with atracurium. In 32 patients, neuromuscular monitoring was performed with a
Myograph 2000 on one hand and a TOF-Guard at the other (M/T group). In 20
patients, monitoring was performed with a Myograph 2000 at both hands (M/M
group). Train-of-four stimulations were applied to the ulnar nerve at the wrist
in both groups. Bias and limits of agreement between the contra lateral hands in
each group were calculated as proposed by Bland and Altman. RESULTS: When the TOF
ratio was 0.25, TOF ratio bias and limits of agreement in the M/T group were 0.86
and 17.58 to -15.85, respectively. Corresponding values in the M/M group were
1.75 and 12.3 to -8.8. Bias in the M/T group decreased significantly to -8.1 when
TOF ratio increased to 0.70, resulting in limits of agreement of 12.1 to -28.4.
The corresponding values in the M/M group were bias 2.0 and limits of agreement
10.7 to -6.7. TOF-Guard bias for onset time and time to 5% recovery of T1 (first
twitch in TOF) were -19s and -1.5 min, respectively; both values differed
significantly from zero (P < 0.05). Taken together with the changing TOF-ratio
bias during recovery in the M/T group, these results indicate different onset and
recovery curves for the two monitoring devices. CONCLUSIONS: Due to wide limits
of agreement and different recovery courses, acccleromyographic and
mechanomyographic recordings of neuromuscular transmission cannot be used
interchangeably. The substantial variation between simultaneous
mechanomyographical recordings of neuromuscular transmission obtained in contra
lateral arms suggests that this factor should be taken into account when studying
new neuromuscular monitoring techniques using the two-arm technique.
PMID- 9641854
TI - Transcranial Doppler blood flow velocity versus 133Xe clearance cerebral blood
flow during mild hypothermic cardiopulmonary bypass.
AB - OBJECTIVE: Transcranial doppler (TCD) is used during cardiopulmonary bypass (CPB)
to assess cerebral emboli and to estimate cerebral perfusion. We sought to
compare TCD middle cerebral artery blood flow velocity (Vmca) to 133Xe clearance
cerebral blood flow (CBF) measurements during mild hypothermic CPB thus
determining its utility in cerebral perfusion assessment. METHODS: Thirty-four
patients undergoing mild hypothermic CPB (35 degrees C) were studied and had
comparisons of Vmca and 133Xe CBF at three time intervals, 10, 30 and 60 min
after the institution of CPB. Linear regression analysis was performed on data
from each of the 3 intervals as well as for pooled data from all 3 periods.
RESULTS: The correlation coefficients for the 3 time periods were, r = 0.32 (p =
0.12), r = 0.32 (p = 0.11), r = 0.48 (p = (0.02), respectively. The pooled data
correlation had a coefficient of 0.34 (p = 0.003). CONCLUSION: These findings
suggest that TCD Vmca is a relatively poor correlate of CBF during mild
hypothermic CPB.
PMID- 9641855
TI - The application of a modified proportional-derivative control algorithm to
arterial pressure alarms in anesthesiology.
AB - OBJECTIVE: We have developed an arterial pressure alarm system based on a
modified proportional-derivative (PD) controller algorithm, and prospectively
tested its ability to predict significant hypotensive episodes, defined as
systolic arterial pressure < 80 mmHg, in comparison to conventional limit alarms.
METHODS: The alarm algorithm was tuned to detect hypotension using selected
invasive arterial pressure traces taken from ten patients who had large intra
operative arterial pressure changes. The algorithm's performance was then tested
prospectively in comparison to conventional limit alarms and median filtered
limit alarms, set at 85 mmHg and 90 mmHg, for its ability to predict hypotensive
episodes in a further 100 patients who required invasive arterial pressure
monitoring. RESULTS: For the PD alarm algorithm, onset times for significant
hypotensive episodes were between those of limit alarms set at 85 mmHg and 90
mmHg. Offset times were similar to the 85 mmHg limit alarms. The false positive
rate was 34% compared with 45-64% for the other alarms (p < 0.01). Using our
definitions, there was one false negative in the PD group, being a 15 second drop
in observed arterial pressure, when a non invasive blood pressure cuff was
inflated above the arterial line. CONCLUSIONS: An arterial pressure alarm system
design based on a closed loop control algorithm offered improved perform ance
over conventional limit alarms and in addition provided a graded output of
severity of the hypotension.
PMID- 9641856
TI - Pulse oximetry monitoring and late postoperative hypoxemia on the general care
floor.
AB - Hypoxemia has long been recognized as a risk to patients in the operating room
and postanesthesia care unit, and hemoglobin oxygen saturation (HbO2) monitoring
with pulse oximetry has become a standard of care in these areas. There is
growing evidence, however, suggesting that later postoperative hypoxemia also may
play a role in organ dysfunction leading to morbidity and mortality. Economic
pressures to move patients earlier from expensive postanesthesia recovery and
intensive care areas to the general care floor -- where nurse-to-patient ratios
are lower and lines of sight and sound may be impaired by walls and curtains --
may lead to inadequate surveillance of at-risk patients. These patient-management
trends underscore the importance of improved monitoring of respiratory status on
the general care floor. In this environment, telemetric pulse oximetry monitoring
may represent a cost-effective approach to maximizing quality of care while
enhancing risk management. This review discusses late postoperative hypoxemia and
identifies areas for further investigation.
PMID- 9641857
TI - Modeling in anesthesia.
AB - A model can be defined as an abstraction of reality which accounts for those
properties ofa phenomenon that are pertinent to the purpose of the model. Models
are used in anesthesia to understand the various physiologic, pharmacological and
physical processes that occur during anesthesia. Indeed, many different types of
models that comply with our definition can be distinguished. Early models
consisted of electrical models of the arterial blood dynamics and cardiovascular
system. Physical models of drug uptake and distribution have been developed to
explain the kinetics of volatile anesthetics in the body. The goal of this paper
is to introduce the reader to some of the types of models that been used to
facilitate education and research in anesthesia. These examples will elucidate
the steps involved in developing a model and the various types of models that
have proven useful.
PMID- 9641858
TI - Anesthetic safety always an issue with obstructive sleep apnea.
PMID- 9641859
TI - Reporting of anesthesia-related incidents: the New Jersey experience.
PMID- 9641860
TI - Debate on reuse of "disposable" medical equipment fueled by FDA.
PMID- 9641861
TI - Continuous monitoring of intraocular pressure is helpful in testing hemodynamic
response to anesthesia and to changes in body position.
PMID- 9641862
TI - Expert weighs factors on reuse of disposables, urges safety criteria and new
studies.
PMID- 9641882
TI - Molecular pattern of ductal pancreatic cancer.
AB - Our understanding of the molecular pathology underlying the development and
progression of ductal pancreatic cancer has been revolutionised during the last 5
years due to the spectacular development of novel molecular biological
techniques. In the present article, we describe key molecular alterations of
sporadic and inherited ductal pancreatic cancer. Overexpression of growth factors
and growth factor receptors are present in a significant proportion of this
tumour type. Mutation of the K-ras oncogene, and disruption of p53 or p16 tumour
suppressor gene abrogates the control of the cyclin-dependent kinases (cdk) and
retinoblastoma (Rb) gene pathway, causing continuous growth of the pancreatic
tumour. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the
inhibitory influence of the transforming growth factor beta signalling pathway.
Lost or decreased expression of retinoid receptors and failure of telomerase
activity may play a role in pancreatic carcinogenesis. Tumour-associated
proteinases, matrix metalloproteinases and plasminogen activators are reported to
be involved in pancreatic cancer invasion and metastasis. Furthermore, the
cytogenetic changes in this cancer are summarised. This molecular pattern
distinguishes pancreatic cancer from other epithelial tumours and represents a
promising basis for the development of diagnostic and other clinical
applications.
PMID- 9641883
TI - Pathology and biology of pancreatic ductal adenocarcinoma.
AB - INTRODUCTION: Ductal adenocarcinoma of the pancreas is a highly aggressive tumor
with early local spread beyond the pancreas, predominantly to the
retroperitoneum, but also with invasion of adjacent great vessels and adjacent
organs. DISCUSSION: Anterior extension may lead to perforation of the visceral
peritoneum and spread within the peritoneal cavity. Cytology in peritoneal lavage
can be positive before any peritoneal metastasis is seen. Invasion of lymphatics
and veins as well as perineural invasion are common. The lymph drainage of the
pancreas is multidirectional to superior, inferior, anterior, posterior and left
lymph nodes. In node-negative cases, isolated tumor cells in the sinus of
regional lymph nodes may be found by immunocytochemistry; such findings must be
distinguished from micrometastasis. The same applies to isolated tumor cells in
bone marrow. PROGNOSIS: The independent prognostic significance of isolated tumor
cells in the regional lymph nodes and in the bone marrow remains to be proven.
For classification of anatomic extent the new, fifth edition ( 1997) of the UICC
TNM classification should be used. The complex Japanese classification cannot be
directly compared with the UICC system. CONCLUSION: Tumor size and histologic
grade influence the extent of spread. Anatomic extent and histologic grade are
the strongest predictors of outcome.
PMID- 9641884
TI - Resection of pancreatic cancer--surgical achievements.
AB - INTRODUCTION: Looking back at the initially dismal record for pancreatic cancer
surgery - Whipple himself felt that a 30-35% mortality was justifiable (!) -
significant progress has been made. PROGRESS: The operative mortality has fallen
below 5% and the serious complications of pancretic resections such as leaks and
haemorrhage have been reduced to some 10% and we are better equipped to deal with
these if they occur. The 5-year-survival of patients in whom pancreatic cancer
was amenable to an R0-resection has risen to 30%. These are the surgical
achievements using the standard Kausch-Whipple technique alone. There has been no
improvement in these results, either by increasing radicality (regional
pancreatectomy) or by reducing it (pylorus-preserving pancreatoduodenectomy). The
same can be said of all other modalities of oncological treatment that have been
tried so far: adjuvant radiochemotherapy, regional chemotherapy, hormonal or
genetic manipulations. PERSPECTIVE: This does not mean that we should reduce
efforts at improving early detection of the disease and unravelling its complex
molecular biology. On the contrary, the results of surgery alone in spite of all
improvements seem to have reached a plateau that gives little cause for
complacency.
PMID- 9641885
TI - Prognostic factors in ductal pancreatic cancer.
AB - INTRODUCTION: The diagnosis of pancreatic adenocarcinoma remains a devastating
life event for most patients and their families. Many patients with this
relatively common malignancy present at a stage of disease not amenable to cancer
directed resectional therapy, and are treated via nonoperative palliative
measures, with median survival of 4-8 months post-diagnosis. CONCLUSION: A
minority of patients present with disease limited to the pancreas and
periampullary region and are candidates for resectional therapy. The prognosis
for these patients is determined by several factors: clinicopathologic staging,
tumor biology and molecular genetics, perioperative factors and the use of
postoperative adjuvant therapy.
PMID- 9641886
TI - Resection and radiochemotherapy of pancreatic cancer--the future?
AB - BACKGROUND: To improve the surgical outcome after resection of pancreatic
adenocarcinomas, multimodal treatment concepts need to be applied and improved.
The controversies among those being pro and contra adjuvant treatment need an up
to-date review of the indications and results achievable with various treatment
modalities. PATIENTS/METHODS: The literature regarding the indications and
results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to
provide a solid base for current recommendations and future developments. The
biology of the disease in the spontaneous course, after surgery and during/after
various palliative and adjuvant/neoadjuvant treatment modalities was focussed on,
to characterise the disease for an optimally targeted treatment in conjunction
with surgical removal of the tumour. The results of systemic and regional
chemotherapy and radiotherapy, either alone or in combination, before, during and
after surgery were critically analysed with respect to the oncological
possibilities and pitfalls of each treatment method. RESULTS: In two randomised
trials, one testing postoperative radiochemotherapy (GITSG), and one
postoperative chemotherapy, the adjuvant treatment achieved a significant
prolongation of the median survival time. The 5-year and 10-year survival rates
were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the
benefit of adjuvant radiochemotherapy. This study had a different design than the
GITSG trial. Several historical control studies supported the beneficial effect
of postoperative radiochemotherapy. In three historical control trials using
regional chemotherapy, one with intraoperative radiotherapy, the survival times
were improved compared with surgery alone. Intraoperative or postoperative
radiotherapy as single modalities might reduce local relapses, but a survival
advantage is still debated. Preoperative neoadjuvant radiochemotherapy has
several advantages (downstaging, devitalising margins and lymph node metastases,
compatibility of treatment vs. postoperative radiochemotherapy), and does not
seem to increase the postoperative morbidity. Several trials have confirmed the
feasibility of this concept, but no survival advantage has yet been proven.
Systemic and regional chemotherapy is able to downstage primarily nonresectable
pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up
to-date protocols can be recommended for routine treatment, if the surgeon or the
patient desires to improve the usually remote prognosis after surgery alone. For
those being indecisive or against adjuvant therapy, the participation in trials,
e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own
positive experience with adjuvant regional chemotherapy and in view of the
postresectional progression pattern, we currently favour adjuvant
radiochemotherapy, with the chemotherapy delivered regionally via the celiac
axis. This concept will be tested against surgery alone in the ESPAC 2 trial.
Neoadjuvant therapies have a great potential, but should be conducted within
studies, such as pre-, intra-, or postoperative radiotherapy.
PMID- 9641887
TI - Quality of life after treatment of pancreatic cancer.
AB - In the past decade there has been increasing focus on assessment of the quality
of life (QoL) of patients with cancer. QoL is now a mandatory endpoint in many
cancer clinical trials, particularly in interventions with palliative intent
alone. Although QoL is difficult to define, a variety of specially designed and
validated questionnaires has been developed to measure QoL in the clinical
setting. In pancreatic cancer, assessment (QoL) is of paramount importance;
however, little research has been conducted and until recently no disease
specific QoL questionnaire existed. In this review we consider the quality of
life of patients with pancreatic cancer, with particular reference to the
symptoms and psychosocial consequences of the disease. The literature is
critically examined on the approaches to evaluation of QoL in previous pancreatic
cancer clinical trials. We then describe the impact on QoL following both
"curative" and palliative surgical interventions and medical treatment, including
endoscopic palliation and chemotherapy for pancreatic cancer. In the European
Organisation for Research and Treatment of Cancer (EORTC) the questionnaire
specific for pancreatic cancer, the QLQ-PAN26, is discussed as a standardised and
valid assessment of QoL in international clinical trials. Finally,
recommendations are made for future QoL research in pancreatic cancer.
PMID- 9641888
TI - Prognostic significance of molecular alterations in human pancreatic carcinoma-
an immunohistological study.
AB - BACKGROUND: During the last decade, many molecular alterations have been
described for pancreatic carcinomas. However, the clinical and prognostic value
of these alterations has been discussed and is controversial. METHODS: An
immunohistochemical study was performed in 82 cases of adenocarcinoma of the
pancreas. Using specific antibodies, expression of EGF, EGF-receptor, cERB-B2,
p53, p21CIP1, cyclin-D1, BCL-2, CD95 and KI67 was evaluated. RESULTS:
Overexpression of the different molecules was found in 44-69% of the pancreatic
carcinomas. With regard to clinico-pathological features, p53 positivity was more
frequently found in advanced and undifferentiated tumours (P<0.05), EGF
overexpression was significantly more frequent in advanced tumours (P<0.05) and
CD95 overexpression was observed to a greater extent in undifferentiated tumours
(P<0.05). Besides cyclin-D1, none of the molecules tested was of prognostic
significance. Patients whose tumours expressed cyclin-DI lived significantly
shorter than patients with cyclin-D1-negative tumours. However, in subgroup
analyses of patients with the same tumour stage or tumour grade, even cyclin-D1.
expression had no prognostic significance. CONCLUSION: These results demonstrate
that the prognostic significance of the molecules tested here is low.
Nevertheless, with regard to tumorigenesis and tumour biology of pancreatic
carcinoma, determination of molecular alterations could provide important
information about pancreatic cancer.
PMID- 9641889
TI - Talc pleurodesis in recurrent pleural effusions.
AB - BACKGROUND AND AIMS: The treatment of recurrent malignant pleural effusions is
known to be difficult and varies from observation in asymptomatic patients to
pleurectomy with varying results. This prospective study presents the efficacy
and the limits of iodized talc pleurodesis in patients with malignant and non
malignant recurrent pleural effusions. METHODS: In a prospective trial talc
pleurodesis was performed in 50 patients with recurrent pleural effusions
(malignant effusions: n=36, non-malignant effusions: n=14). After insertion of a
chest tube and complete re-expansion of the lung, 5 mg of talc and 3 mg of thymol
iodine were installed with 0.5 ml of 1% xylocaine/kg body weight and 30 ml 0.9%
saline solution. The chest tube was removed after an average time of 4 days and
chest radiographs were performed 1 month after instillation to evaluate the
efficacy of pleurodesis. RESULTS: Successful therapy was achieved in 31 of 33
patients (94%) with malignant effusions within a follow-up period of 7 months.
Three patients died within 1 month after therapy due to progressive malignant
disease. The treatment was successful in all cases of non-malignant effusions and
complications did not occur in either group. CONCLUSIONS: These results indicate
that pleurodesis with iodized talcum slurry is a simple and inexpensive method
with high efficacy in controlling malignant and non-malignant pleural effusions.
PMID- 9641890
TI - Positron emission tomography with F-18-deoxyglucose in patients with
differentiated thyroid carcinoma, elevated thyroglobulin levels, and negative
iodine scans.
AB - INTRODUCTION: In patients with differentiated thyroid carcinoma, elevated serum
levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic
procedures and in particular in spite of a negative iodine-131 scan. Positron
emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful
method for the detection of metastatic lesions or the recurrence of thyroid
cancer. We aimed to investigate whether FDG-PET is capable of detecting
metastatic lesions or recurrence in patients with differentiated thyroid
carcinoma, elevated serum levels of thyroglobulin, and otherwise negative
diagnostic procedures, including the iodine-131 scan. METHODS: From a group of
500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had
elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and
abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients
(hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was
performed. All but one FDG-PET study was performed in a state of hypothyroidism
(TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml).
RESULTS: In 6 of the 12 patients investigated, the FDG-PET was positive. In three
of the patients, the diagnosis was confirmed by computed tomography or magnetic
resonance imaging. In patients with a positive FDG-PET finding, the hTg level was
146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients
with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17
ng/ml, median 8.1 ng/ml), P=0.01. CONCLUSION: These preliminary results show that
in patients with differentiated thyroid carcinoma, elevated hTg levels, and
otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in
detecting metastatic lesions.
PMID- 9641891
TI - The role of fine-needle aspiration cytology and frozen section histology in
management of differentiated thyroid cancer: the UK experience.
AB - OBJECTIVE: A review of the literature was undertaken to determine the use by UK
surgeons of fine-needle aspiration cytology (FNAC) and frozen section histology
in management of differentiated thyroid carcinoma. RESULTS: The extent of FNAC
use was highly variable, but commoner amongst more specialised surgeons who
performed more than 25 thyroid operations per year. Such surgeons generally
perform ipsilateral total lobectomy and isthmectomy for solitary thyroid nodule
and use FNAC to assist in planning surgical strategy for differentiated thyroid
cancer mainly by determining the likely extent of contralateral lobe resection
and nodal dissection required. The use of frozen section histology to aid this
decision intra-operatively is largely unreported in the UK literature.
PMID- 9641892
TI - Morbidity of prophylactic lymph node dissection in the central neck area in
patients with papillary thyroid carcinoma.
AB - The benefits of prophylactic central neck dissection (PCND) in patients with
papillary thyroid carcinoma (PTC) have not been clearly demonstrated so far and
should be weighed against the potential risks of the procedure. The aim of the
study was to assess the recurrent laryngeal nerve and parathyroid risks of PCND
after total thyroidectomy in patients with PTC and to compare the results with
those obtained in patients who underwent total thyroidectomy only. METHODS: We
selected 100 patients who underwent a total thyroidectomy: 50 for nontoxic benign
multinodular goiter (Group 1) and 50 for PTC (Group 2). Patients with PTC had no
evidence of macroscopic lymph node invasion during surgery and underwent, in
addition to the total thyroidectomy, a PCND. All of the 100 patients were
operated on by two experienced endocrine surgeons. All patients had pre- and
postoperative investigations of vocal cord movements. Calcemia and phosphoremia
were systematically evaluated preoperatively and on day 1 and day 2 after
surgery. All patients presenting a postoperative calcemia below 1.90 mmol/l were
considered to present an early postoperative hypoparathyroidism and received
calcium-vitamin D therapy. The hypoparathyroidism was considered permanent when
calcium-vitamin D therapy was still necessary 1 year after surgery. RESULTS: None
of the patients presented permanent nerve palsy. There were three cases of
transient nerve palsy (6%) in Group 1 and two (4%) in Group 2. In Group 1 there
was no permanent hypoparathyroidism and four cases of transient
hypoparathyroidism (8%). In Group 2, seven patients presented transient
hypoparathyroidism (14%) and two patients (4%) remained with definitive
hypoparathyroidism. CONCLUSION: After total thyroidectomy for PTC, PCND does not
increase recurrent laryngeal nerve morbidity but it is responsible for a high
rate of hypoparathyroidism, especially in the early postoperative course. Even
taking into account the possible benefits, the results make it difficult to
advocate PCND as a routine procedure in all patients presenting a PTC.
PMID- 9641893
TI - Prophylactic thyroidectomy in MEN IIA: does the calcitonin level correlate with
tumor spread?
AB - BACKGROUND: The fate of patients with multiple endocrine neoplasia of type II A
(MEN II A) is determined by medullary thyroid carcinoma, which occurs in all
cases. This has led to the therapeutic concept of prophylactic thyroidectomy in
affected family members with the goal of removing the thyroid before the
manifestation of carcinoma. We investigated a prophylactically thyroidectomized
MEN II A population to determine whether the highly specific and sensitive tumor
marker calcitonin correlates with tumor spread. PATIENTS AND METHODS: Fifteen
patients with MEN II A (aged 4-24 years) who had undergone prophylactic
thyroidectomy since 1990 were included in the study. Baseline and pentagastrin
stimulated calcitonin levels were preoperatively determined in all cases. The
indication for surgery was established on the basis of pathologic calcitonin
levels in the first seven patients and on the basis of detected RET proto
oncogene mutation in the other eight patients. Bilateral central lymphadenectomy
was performed in all patients in addition to thyroidectomy. RESULTS: Histology
demonstrated C-cell hyperplasia in five patients (aged 4-13 years), unilateral
medullary microcarcinoma in six (aged 9-17 years) and a bilateral medullary
microcarcinoma in three cases (aged 17-24 years). One 9-year-old boy with
bilateral microcarcinoma already had a lymph node metastasis. The mean baseline
calcitonin level correlated with the histologic findings (r=0.71, P=0.003) but
there was no correlation between pentagastrin-stimulated calcitonin levels and
histology (r=0.21, P=0.47). CONCLUSION: In MEN II A patients undergoing
prophylactic thyroidectomy, baseline but not stimulated calcitonin levels already
correlate with the histologic tumor stage at the stage of clinically occult C
cell hyperplasia or medullary microcarcinoma. However, biochemical screening
cannot reliably discriminate the transition from C-cell hyperplasia to invasive
microcarcinoma. Individuals with MEN IIA should therefore undergo early
prophylactic thyroidectomy once the diagnosis is confirmed by molecular genetic
testing.
PMID- 9641894
TI - Reoperation for persistent or recurrent primary hyperparathyroidism.
AB - AIM: To analyse the causes and outcome of reoperations for persistent or
recurrent primary hyperparathyroidism (HPT). MATERIALS AND METHODS: We reviewed
the medical records of 38 patients who underwent reoperation between December
1965 and April 1997 for persistent or recurrent primary HPT. During this period
of time, 1448 patients underwent operation for primary HPT, 294 for renal HPT and
58 for questionable disease, i. e. a total of 1800. In the 1448 cases of HPT, 22
patients were reoperated after a first cervicotomy in the institution, i. e. a
first reoperation rate of 1.5%. Sixteen patients were referred after unsuccessful
parathyroid surgery. Six patients were reoperated on twice and one patient seven
times for a graft-dependent recurrence. RESULTS: Reasons for failed parathyroid
operations included tumour tissue in ectopic location (75%) or tumour tissue that
had not been seen in normal position (19%), parathyreomatosis (2%), parathyroid
cancer (2%) and graft-dependent hypercalcaemia (2%). Of the ectopic glands, 45 %
were intrathymic, 12.5% intrathyroidal, 7.5% retro-oesophageal, 7.5% in the
carotid sheath, 5% interthyrotracheal, 5% in the mediastinum (extrathymic), 5% in
the aorto-pulmonary window, 2.5% undescended, 2.5% overdescended and 2.5%
intertracheooesophageal. Of the patients, 38% had uniglandular lesions, 60%
multiglandular lesions, and 2% parathyroid cancer. The histologically confirmed
cause of HPT was adenoma in 50% of cases, hyperplasia in 38% and "normal" but
overweight glands in 9.5%. Of the 38 patients studied, 15 presented one or more
supernumerary glands (fifth to eighth gland). Reoperation was performed through a
cervical incision in 82% of cases and using a mediastinal approach in 18% (8
median sternotomies, 1 thoracoscopy). The success rate of the reoperations was
92%. A total of 8% of patients suffered permanent unilateral vocal cord
paralysis; 5% are definitely hypocalcaemic. The sensitivities of preoperative
localization studies ranged from 69% for sestamibi scan and 63% for selective
venous catheterization to 16% for computed tomography. CONCLUSION: Repeated
parathyroidectomy can be avoided in more than 98% of patients if an experienced
surgeon performs bilateral cervical exploration during the initial parathyroid
operation. For patients with persistent or recurrent primary HPT, preoperative
localization studies and a focused surgical approach can result in a 92% success
rate with a minimal complication rate.
PMID- 9641895
TI - Long-term follow-up of node-positive papillary thyroid carcinomas.
AB - INTRODUCTION: We retrospectively reviewed the data of patients with papillary
thyroid cancer who were node positive and treated at our department between 1955
and 1994. Of 362 cases of papillary cancer, 134 were identified with lymph-node
metastases (37%). METHODS: Two types of dissection procedures were applied by a
large community of surgeons. When only the cervical central lymph nodes were
involved, the procedure of choice was thyroidectomy, with local lymph-node
excision (LD); if the lateral nodes were also affected, modified radical neck
dissection (MRND) was applied. RESULTS: Of 88 patients considered to have minimal
involvement, 70 underwent procedures of a lesser magnitude than MRND. Most of the
operations were localised "picking procedures". Recurrence of the disease
developed in 16 cases, twice in 8 of these. The new tumourous lymph node was
found to be ipsilateral in every case and close to the place of the first
operation. The rate of recurrence was 23%. In the same group, 18 MRNDs were
performed, with ipsilateral lymph-node recurrence in six cases. In 41 patients
undergoing surgery for extended lymph-node metastases, conservative excisions
were carried out in 17 and MRND in 24 cases, including six bilateral dissections.
In this group, late recurrence was 47%. CONCLUSION: The results of the follow-up
of 30 childhood and juvenile patients with papillary thyroid carcinoma is very
interesting; all of our young patients are alive.
PMID- 9641896
TI - Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia
type 1.
AB - INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
disorder characterized by the development of multiple endocrine adenomas,
typically in the pancreas, anterior pituitary, and parathyroid glands. The
disease is associated with germ-line mutations of the menin gene, a putative
tumor-suppressor gene located on human chromosome 11q13. METHODS: To facilitate
the diagnosis and prediction of MEN1 in patients and their relatives, we
developed a molecular two-step strategy to screen for menin gene mutations. DNA
fragments covering the entire menin coding sequence are generated from patient
cDNA by polymerase reaction (PCR) and subsequently analyzed by single-strand
conformational polymorphism electrophoresis (SSCP). Fragments with aberrant SSCP
migration are DNA-sequenced to directly characterize menin mutations. In a second
diagnostic step, genomic DNA of healthy relatives of the corresponding MEN1 index
patient is analyzed by PCR, with only the specific exon amplified harboring the
family-specific mutation. Mutation-specific restriction enzyme digestion of this
PCR product finally allows the identification of mutation carriers through
pathological restriction fragment patterns. RESULTS: Using this approach, we
identified an in-frame deletion mutation (delta Tyr Met) located in menin exon 4
(codon 227-228) that co-segregates with the disease phenotype in a large MEN1
family from Southern Germany. CONCLUSION: It is likely that the direct molecular
analysis of menin gene mutations will replace the genetic and biochemical
screening tests currently used in the clinical management of MEN1 families. In
addition, these studies may provide clues to the tumor biology of both sporadic
and MEN1-associated endocrine adenomas.
PMID- 9641897
TI - Histological verification of positive fluorine-18 fluorodeoxyglucose findings in
patients with differentiated thyroid cancer.
AB - Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a
new imaging modality used in the follow-up of patients with differentiated
thyroid cancer if the results of (131)I scintigraphy are negative in spite of an
elevated thyroglobulin level. The aim of this retrospective analysis was to
estimate the value of FDG-PET regarding the operability of patients with positive
findings. From January 1994 to October 1997, we investigated 60 patients with
differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on
after positive findings. Most of these lesions were suspected of having lymph
node involvement or local recurrences in the thyroid bed. One patient showed a
solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13
patients confirmed the suspected involvement of thyroid cancer. The false
positive findings were caused by inflamed lymph nodes in two cases and benign
thymus tissue in one case. We conclude that PET is a useful diagnostic tool to
guide early surgical therapy in patients with (131)I negative differentiated
thyroid carcinoma.
PMID- 9641898
TI - Ampullectomy for adenoma of the papilla and ampulla of Vater.
AB - INTRODUCTION: The frequency of malignant adenomas of the papilla figures between
15 and 30%. Villous adenoma is considered to be a premalignant lesion. TREATMENT:
Resection of the papilla is indicated in large tubular and small tubulovillous
adenoma. Ampullectomy, however, is mandatory in villous adenoma with severe
dysplasia and large villous or tubulovillous adenoma. If villous adenoma with a
low-risk pT1 N0 M0 G1/2-cancer is treated by ampullectomy, local lymph dissection
should also be performed. Ampullectomy includes extirpation of the ampulla of
Vater and reinsertion of the common bile duct and the pancreatic main duct into
the duodenal wall. RESULTS: Hospital mortality after ampullectomy is less than
0.4%, and surgical morbidity, e.g., cholangitis, below 10%.
PMID- 9641899
TI - A vision of surgery: the concept OP 2000.
PMID- 9641906
TI - Plasticity induced by shock waves in nonequilibrium molecular-dynamics
simulations
AB - Nonequilibrium molecular-dynamics simulations of shock waves in three-dimensional
10-million atom face-centered cubic crystals with cross-sectional dimensions of
100 by 100 unit cells show that the system slips along all of the available 111
slip planes, in different places along the nonplanar shock front. Comparison of
these simulations with earlier ones on a smaller scale not only eliminates the
possibility that the observed slippage is an artifact of transverse periodic
boundary conditions, but also reveals the richness of the nanostructure left
behind. By introducing a piston face that is no longer perfectly flat, mimicking
a line or surface inhomogeneity in the unshocked material, it is shown that for
weaker shock waves (below the perfect-crystal yield strength), stacking faults
can be nucleated by preexisting extended defects.
PMID- 9641907
TI - Design and fabrication of topologically complex, three-dimensional
microstructures
AB - Two concepts for use in the fabrication of three-dimensional (3D) microstructures
with complex topologies are described. Both routes begin with a two-dimensional
(2D) pattern and transform it into a 3D microstructure. The concepts are
illustrated by use of soft lithographic techniques to transfer 2D patterns to
cylindrical (pseudo-3D) substrates. Subsequent steps-application of uniaxial
strain, connection of patterns on intersecting surfaces-transform these patterns
into free-standing, 3D, noncylindrically symmetrical microstructures.
Microelectrodeposition provides an additive method that strengthens thin metal
designs produced by patterning, welds nonconnected structures, and enables the
high-strain deformations required in one method to be carried out successfully.
PMID- 9641908
TI - From shifting silt to solid stone: the manufacture of synthetic basalt in ancient
mesopotamia
AB - Slabs and fragments of gray-black vesicular "rock," superficially resembling
natural basalt but distinctive in chemistry and mineralogy, were excavated at the
second-millennium B.C. Mesopotamian city of Mashkan-shapir, about 80 kilometers
south of Baghdad, Iraq. Most of this material appears to have been deliberately
manufactured by the melting and slow cooling of local alluvial silts. The high
temperatures (about 1200 degreesC) required and the large volume of material
processed indicate an industry in which lithic materials were manufactured
("synthetic basalt") for grinding grain and construction.
PMID- 9641909
TI - (Mg,Fe)SiO3-perovskite stability under lower mantle conditions
AB - In three different experiments up to 100 gigapascals and 3000 kelvin, (Mg,Fe)SiO3
perovskite, the major component of the lower mantle, remained stable and did not
decompose to its component oxides (Mg, Fe)O and SiO2. Perovskite was formed from
these oxides when heated in a diamond anvil cell at pressures up to 100
gigapascals. Both MgSiO3 crystals and glasses heated to 3000 kelvin at 75
gigapascals also formed perovskite as a single phase, as evident from Raman
spectra. Moreover, fluorescence measurements on chromium-doped samples
synthesized at these conditions gave no indication of the presence of MgO.
PMID- 9641911
TI - Gold nanoelectrodes of varied size: transition to molecule-like charging
AB - A transition from metal-like double-layer capacitive charging to redox-like
charging was observed in electrochemical ensemble Coulomb staircase experiments
on solutions of gold nanoparticles of varied core size. The monodisperse gold
nanoparticles are stabilized by short-chain alkanethiolate monolayers and have 8
to 38 kilodaltons core mass (1.1 to 1.9 nanometers in diameter). Larger cores
display Coulomb staircase responses consistent with double-layer charging of
metal-electrolyte interfaces, whereas smaller core nanoparticles exhibit redox
chemical character, including a large central gap. The change in behavior is
consistent with new near-infrared spectroscopic data showing an emerging gap
between the highest occupied and lowest unoccupied orbitals of 0.4 to 0.9
electron volt.
PMID- 9641910
TI - Perennial Antarctic lake ice: an oasis for life in a polar desert.
AB - The permanent ice covers of Antarctic lakes in the McMurdo Dry Valleys develop
liquid water inclusions in response to solar heating of internal aeolian-derived
sediments. The ice sediment particles serve as nutrient (inorganic and organic)
enriched microzones for the establishment of a physiologically and ecologically
complex microbial consortium capable of contemporaneous photosynthesis, nitrogen
fixation, and decomposition. The consortium is capable of physically and
chemically establishing and modifying a relatively nutrient- and organic matter
enriched microbial "oasis" embedded in the lake ice cover.
PMID- 9641912
TI - Giant electrostriction and relaxor ferroelectric behavior in electron-irradiated
poly(vinylidene fluoride-trifluoroethylene) copolymer
AB - An exceptionally high electrostrictive response ( approximately 4 percent) was
observed in electron-irradiated poly(vinylidene fluoride-trifluoroethylene)
[P(VDF-TrFE)] copolymer. The material exhibits typical relaxor ferroelectric
behavior, suggesting that the electron irradiation breaks up the coherent
polarization domain (all-trans chains) in normal ferroelectric P(VDF-TrFE)
copolymer into nanopolar regions (nanometer-size, all-trans chains interrupted by
trans and gauche bonds) that transform the material into a relaxor ferroelectric.
The expanding and contracting of these polar regions under external fields,
coupled with a large difference in the lattice strain between the polar and
nonpolar phases, generate an ultrahigh strain response.
PMID- 9641913
TI - Neptune's eccentricity and the nature of the kuiper belt
AB - The small eccentricity of Neptune may be a direct consequence of apsidal wave
interaction with the trans-Neptune population of debris called the Kuiper belt.
The Kuiper belt is subject to resonant perturbations from Neptune, so that the
transport of angular momentum by density waves can result in orbital evolution of
Neptune as well as changes in the structure of the Kuiper belt. In particular,
for a belt eroded out to the vicinity of Neptune's 2:1 resonance at about 48
astronomical units, Neptune's eccentricity can damp to its current value over the
age of the solar system if the belt contains slightly more than an earth mass of
material out to about 75 astronomical units.
PMID- 9641914
TI - Embryonic folate metabolism and mouse neural tube defects.
AB - Folic acid prevents 70 percent of human neural tube defects (NTDs) but its mode
of action is unclear. The deoxyuridine suppression test detects disturbance of
folate metabolism in homozygous splotch (Pax3) mouse embryos that are developing
NTDs in vitro. Excessive incorporation of [3H]thymidine in splotch embryos
indicates a metabolic deficiency in the supply of folate for the biosynthesis of
pyrimidine. Exogenous folic acid and thymidine both correct the biosynthetic
defect and prevent some NTDs in splotch homozygotes, whereas methionine has an
exacerbating effect. These data support a direct normalization of neurulation by
folic acid in humans and suggest a metabolic basis for folate action.
PMID- 9641915
TI - p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13.
AB - Members of the regulators of G protein signaling (RGS) family stimulate the
intrinsic guanosine triphosphatase (GTPase) activity of the alpha subunits of
certain heterotrimeric guanine nucleotide-binding proteins (G proteins). The
guanine nucleotide exchange factor (GEF) for Rho, p115 RhoGEF, has an amino
terminal region with similarity to RGS proteins. Recombinant p115 RhoGEF and a
fusion protein containing the amino terminus of p115 had specific activity as
GTPase activating proteins toward the alpha subunits of the G proteins G12 and
G13, but not toward members of the Gs, Gi, or Gq subfamilies of Galpha proteins.
This GEF may act as an intermediary in the regulation of Rho proteins by G13 and
G12.
PMID- 9641916
TI - Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by
Galpha13.
AB - Signaling pathways that link extracellular factors to activation of the monomeric
guanosine triphosphatase (GTPase) Rho control cytoskeletal rearrangements and
cell growth. Heterotrimeric guanine nucleotide-binding proteins (G proteins)
participate in several of these pathways, although their mechanisms are unclear.
The GTPase activities of two G protein alpha subunits, Galpha12 and Galpha13, are
stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated
Galpha13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze
nucleotide exchange on Rho. In contrast, activated Galpha12 inhibited stimulation
by Galpha13. Thus, p115 RhoGEF can directly link heterotrimeric G protein alpha
subunits to regulation of Rho.
PMID- 9641917
TI - Type IV pili, transient bacterial aggregates, and virulence of enteropathogenic
Escherichia coli.
AB - Type IV bundle-forming pili of enteropathogenic Escherichia coli are required for
the localized adherence and autoaggregation phenotypes. Whether these pili are
also required for virulence was tested in volunteers by inactivating bfpA or bfpT
(perA) encoding, respectively, the pilus subunit and the bfp operon
transcriptional activator. Both mutants caused significantly less diarrhea.
Mutation of the bfpF nucleotide-binding domain caused increased piliation,
enhanced localized adherence, and abolished the twitching motility-dispersal
phase of the autoaggregation phenotype. The bfpF mutant colonized the human
intestine but was about 200-fold less virulent. Thus, BfpF is required for
dispersal from the bacterial aggregate and for full virulence.
PMID- 9641918
TI - Drosophila synapse formation: regulation by transmembrane protein with Leu-rich
repeats, CAPRICIOUS.
AB - Upon reaching the target region, neuronal growth cones transiently search through
potential targets and form synaptic connections with only a subset of these. The
capricious (caps) gene may regulate these processes in Drosophila. caps encodes a
transmembrane protein with leucine-rich repeats (LRRs). During the formation of
neuromuscular synapses, caps is expressed in a small number of synaptic partners,
including muscle 12 and the motorneurons that innervate it. Loss-of-function and
ectopic expression of caps alter the target specificity of muscle 12
motorneurons, indicating a role for caps in selective synapse formation.
PMID- 9641919
TI - Abolition of long-term stability of new hippocampal place cell maps by NMDA
receptor blockade.
AB - Hippocampal pyramidal cells are called place cells because each cell tends to
fire only when the animal is in a particular part of the environment-the cell's
firing field. Acute pharmacological blockade of N-methyl-D-aspartate (NMDA)
glutamate receptors was used to investigate how NMDA-based synaptic plasticity
participates in the formation and maintenance of the firing fields. The results
suggest that the formation and short-term stability of firing fields in a new
environment involve plasticity that is independent of NMDA receptor activation.
By contrast, the long-term stabilization of newly established firing fields
required normal NMDA receptor function and, therefore, may be related to other
NMDA-dependent processes such as long-term potentiation and spatial learning.
PMID- 9641920
TI - Edge effects and the extinction of populations inside protected areas
AB - Theory predicts that small populations may be driven to extinction by random
fluctuations in demography and loss of genetic diversity through drift. However,
population size is a poor predictor of extinction in large carnivores inhabiting
protected areas. Conflict with people on reserve borders is the major cause of
mortality in such populations, so that border areas represent population sinks.
The species most likely to disappear from small reserves are those that range
widely-and are therefore most exposed to threats on reserve borders-irrespective
of population size. Conservation efforts that combat only stochastic processes
are therefore unlikely to avert extinction.
PMID- 9641921
TI - Insecticidal toxins from the bacterium Photorhabdus luminescens.
AB - Transgenic plants expressing Bacillus thuringiensis (Bt) toxins are currently
being deployed for insect control. In response to concerns about Bt resistance,
we investigated a toxin secreted by a different bacterium Photorhabdus
luminescens, which lives in the gut of entomophagous nematodes. In insects
infected by the nematode, the bacteria are released into the insect hemocoel; the
insect dies and the nematodes and bacteria replicate in the cadaver. The toxin
consists of a series of four native complexes encoded by toxin complex loci tca,
tcb, tcc, and tcd. Both tca and tcd encode complexes with high oral toxicity to
Manduca sexta and therefore they represent potential alternatives to Bt for
transgenic deployment.
PMID- 9641922
TI - All changed, changed utterly. British medicine will be transformed by the Bristol
case.
PMID- 9641923
TI - Central venous catheters-time for a change?. If you put them in properly you
don't need to change them routinely.
PMID- 9641924
TI - Controversy in managing patients with prostate cancer. Banish dogma, get more
data.
PMID- 9641925
TI - Taking precautions with ACE inhibitors. A theoretical risk exists in patients
with unilateral renal artery stenosis.
PMID- 9641926
TI - Improving doctor-patient communication. Not an option, but a necessity.
PMID- 9641927
TI - Annual league tables of mortality in neonatal intensive care units: longitudinal
study. International Neonatal Network and the Scottish Neonatal Consultants and
Nurses Collaborative Study Group.
AB - OBJECTIVE: To assess whether crude league tables of mortality and league tables
of risk adjusted mortality accurately reflect the performance of hospitals.
DESIGN: Longitudinal study of mortality occurring in hospital. SETTING: 9
neonatal intensive care units in the United Kingdom. SUBJECTS: 2671 very low
birth weight or preterm infants admitted to neonatal intensive care units between
1988 and 1994. MAIN OUTCOME MEASURES: Crude hospital mortality and hospital
mortality adjusted using the clinical risk index for babies (CRIB) score.
RESULTS: Hospitals had wide and overlapping confidence intervals when ranked by
mortality in annual league tables; this made it impossible to discriminate
between hospitals reliably. In most years there was no significant difference
between hospitals, only random variation. The apparent performance of individual
hospitals fluctuated substantially from year to year. CONCLUSIONS: Annual league
tables are not reliable indicators of performance or best practice; they do not
reflect consistent differences between hospitals. Any action prompted by the
annual league tables would have been equally likely to have been beneficial,
detrimental, or irrelevant. Mortality should be compared between groups of
hospitals using specific criteria-such as differences in the volume of patients,
staffing policy, training of staff, or aspects of clinical practice-after
adjusting for risk. This will produce more reliable estimates with narrower
confidence intervals, and more reliable and rapid conclusions.
PMID- 9641928
TI - Effect of flutamide on survival in patients with pancreatic cancer: results of a
prospective, randomised, double blind, placebo controlled trial.
AB - OBJECTIVES: To assess whether flutamide (Drogenil), a pure androgen receptor
blocking agent, improves survival in patients with pancreatic carcinoma and thus
whether testosterone is a major growth factor for this tumour. DESIGN: A
prospective, randomised, double blind placebo controlled trial. SUBJECTS: 49
patients with a clinical diagnosis of pancreatic carcinoma. INTERVENTIONS: 24
patients received flutamide and 25 received placebo. MAIN OUTCOME MEASURES: Death
of the patient. RESULTS: Analysis of all patients at 6 months and 1 year showed
14 and eight patients alive, respectively, in the flutamide group compared with
10 and one in the placebo group. After exclusion of those patients in both groups
who received less than 6 weeks' treatment because of advanced disease and early
death the comparable results were 14 (88%) and eight (50%) alive in the flutamide
group compared with 10 (50%) and one (5%) in the placebo group. Median survival
for all patients was 8 months in the flutamide group compared with 4 months in
the placebo group. With the 6 week exclusions median survival was 12 months
compared with 5 months, respectively. CONCLUSIONS: This study supports the
concept that testosterone is a growth factor for pancreatic carcinoma and that
blockade of androgen receptors offers an appropriate new approach to treatment.
PMID- 9641929
TI - Effectiveness of home care programmes for patients with incurable cancer on their
quality of life and time spent in hospital: systematic review.
AB - OBJECTIVE: To investigate whether for patients with incurable cancer
comprehensive home care programmes are more effective than standard care in
maintaining the patients' quality of life and reducing their "readmission time"
(percentage of days spent in hospital from start of care till death). DESIGN:
Systematic review. METHODS: A computer aided search was conducted using the
databases of Medline, Embase, CancerLit, and PsychLit. The search for studies and
the assessment of the methodological quality of the relevant studies were
performed by two investigators, blinded from each other. Prospective, controlled
studies investigating the effects of a home care intervention programme on
patients' quality of life or on readmission time were included in the analyses.
RESULTS: Only 9 prospective controlled studies were found; eight were performed
in the United States and 1 in the United Kingdom. Their methodological quality
was judged to be moderate (median rating 62 on a 100 point scale). None of the
studies showed a negative influence of home care interventions on quality of
life. A significantly positive influence on the outcome measures was seen in 2
out of the 5 studies measuring patients' satisfaction with care, in 3/7 studies
measuring physical dimensions of quality of life, in 1/6 studies measuring
psychosocial dimensions, and in 2/5 studies measuring readmission time. The
incorporation of team members' visits to patients at home or regular
multidisciplinary team meetings into the intervention programme seemed to be
related to positive results. CONCLUSIONS: The effectiveness of comprehensive home
care programmes remains unclear. Given the enormity of the problems faced by
society in caring for patients with terminal cancer, further research is urgently
needed.
PMID- 9641930
TI - Routine replacement of central venous catheters: telephone survey of intensive
care units in mainland Britain.
PMID- 9641931
TI - Questionnaire study of effect of sex and age on the prevalence of wheeze and
asthma in adolescence.
PMID- 9641932
TI - Seasonal variation in coronary artery disease mortality in Hawaii: observational
study.
PMID- 9641935
TI - Italian duels
PMID- 9641933
TI - Effect of educational leaflets and questions on knowledge of contraception in
women taking the combined contraceptive pill: randomised controlled trial.
AB - OBJECTIVE: To assess whether provision of educational leaflets or questions on
contraception improves knowledge of contraception in women taking the combined
contraceptive pill. DESIGN: Randomisation of women into three groups according to
type of educational leaflet on contraceptive information. These groups were
subdivided into two on the basis of questions on contraception asked by the
doctor or practice nurse. The women were followed up by postal questionnaire 3
months later. SETTING: 15 general practices in South and West region. SUBJECTS:
636 women attending check up appointment for repeat prescription of the combined
contraceptive pill. MAIN OUTCOME MEASURES: Knowledge of: factors causing pill
failure, subsequent action, emergency contraception, and all the rules (pill
rules) that apply to the contraceptive pill. RESULTS: 523 women returned
completed questionnaires (response rate 82%). Knowledge of contraception with no
intervention was low with only 10 (12%) women knowing all the pill rules.
Educational intervention had a highly significant effect on knowledge of: factors
causing pill failure (likelihood ratio chi2=22); subsequent action (21);
emergency contraception (24); and all the pill rules (22) (P<0.01 in all cases).
Improvement in knowledge of all the pill rules occurred with provision of the
summary leaflet (28% knew all the rules, adjusted odds ratio 4.04, 95% confidence
interval 1.68 to 9.75), the Family Planning Association's leaflet (27%, 3.43,
1.45 to 8.09), and asking questions (26%, 3.03, 1.30 to 7.00). Asking questions
in addition to provision of leaflets improved knowledge of contraception further
for the summary leaflet (39%, 6.81, 2.85 to 16.27) but not for the Family
Planning Association leaflet (21%, 2.58, 1.07 to 6.18). CONCLUSION: Women
attending check ups for repeat prescriptions of the contraceptive pill should be
provided with educational leaflets on contraception or asked relevant questions
to help improve their knowledge of contraception. Asking questions in addition to
providing a summary leaflet is time consuming, but results in the most knowledge
gained.
PMID- 9641936
TI - Non-specific but effective
PMID- 9641934
TI - Contracting for general practice: another turn of the wheel of history.
PMID- 9641937
TI - Communicating the risk reduction achieved by cholesterol reducing drugs.
PMID- 9641939
TI - Netlines
PMID- 9641938
TI - Evaluating information technology in health care: barriers and challenges.
PMID- 9641940
TI - Alternative definitions
PMID- 9641941
TI - Tuberculosis.
PMID- 9641942
TI - Retracing the Oregon trail: the experience of rationing and the Oregon health
plan.
PMID- 9641943
TI - Spectre of racism in health and health care: lessons from history and the United
States.
PMID- 9641944
TI - Managing demand at the interface between primary and secondary care.
PMID- 9641945
TI - The new NHS: the octopus
PMID- 9641946
TI - The new NHS: No patchwork for health centres
PMID- 9641947
TI - Racial discrimination in distinction awards. Discrimination is probably indirect.
PMID- 9641948
TI - Only one quarter of women with learning disability in Exeter have cervical
screening.
PMID- 9641949
TI - Screening for breast cancer is necessary in patients with learning disability.
PMID- 9641950
TI - Co-proxamol is effective in chronic pain.
PMID- 9641951
TI - Mefloquine to prevent malaria. Interpretation of study was not based on evidence.
PMID- 9641952
TI - Passive smoking in pregnancy.
PMID- 9641953
TI - Causes of regional differences in air pollution effects are being studied
further.
PMID- 9641954
TI - Six months' follow up after occupational exposure to HIV is usually long enough.
PMID- 9641955
TI - Acute pancreatitis. Normal serum amylase does not exclude severe acute
pancreatitis.
PMID- 9641956
TI - Opiate detoxification under anaesthesia.
PMID- 9641957
TI - Clinical experience and performance in final examinations. Teaching styles need
to be reviewed to help students with inappropriate learning styles.
PMID- 9641958
TI - Earlier study of effect on healthcare costs of preventing fatal diseases yielded
similar results.
PMID- 9641959
TI - Lessons of a hip failure. Registers of joint replacement operations should be set
up.
PMID- 9641960
TI - Cardiac surgical services in Bristol are now of high quality.
PMID- 9641962
TI - Out of area treatments will replace ECRs
PMID- 9641961
TI - John parker
PMID- 9641963
TI - The long march
PMID- 9641965
TI - A profession on probation
PMID- 9641964
TI - There must be a better way
PMID- 9641967
TI - League tables are inaccurate in ranking hospital mortality outcomes
PMID- 9641966
TI - Fillers
PMID- 9641969
TI - Benefits of home care for incurable cancer are unclear
PMID- 9641968
TI - Flutamide improves survival in pancreatic cancer
PMID- 9641970
TI - Half of british ITUs routinely replace central venous catheters
PMID- 9641971
TI - Wheeze becomes more prevalent in girls than boys at about the age of 12
PMID- 9641972
TI - Knowledge about contraception can be improved through leaflets and questions
PMID- 9641973
TI - Macromolecular assembly and secretion across the bacterial cell envelope: type II
protein secretion systems.
AB - A decade ago, Pugsley and colleagues reported the existence of a large region of
Klebsiella DNA, distinct from the Klebsiella gene encoding pullulanase, which was
necessary for secretion of this enzyme to the cell surface in Escherichia coli
(d'Enfert et al., 1987a,b). The pul genes it contained proved to be the tip of an
iceberg. The sequences reported before 1992 (d'Enfert et al., 1987a,b; d'Enfert &
Pugsley, 1989; Pugsley & Reyss, 1990; Reyss & Pugsley, 1990) included only one
gene (pulD) that matched any sequence in the data base; a 220 amino acid residue
segment of PulD was 32% identical with a portion of the filamentous phage-encoded
protein, pIV. But by the time the sequence of the 18.8 kb DNA fragment that
contained the pul genes had been completed (Possot et al., 1992), reports of sets
of homologous genes in several species of Gram-negative plant and animal
pathogens had appeared. For the most part, these gene clusters were cloned by
their ability to complement mutants that produced, but failed to secrete,
proteins normally found in the extracellular milieu; when tested, the mutants
showed reduced pathogenicity or were totally avirulent. The secreted proteins
included hydrolytic enzymes such as cellulase and pectinase from plant pathogens,
and proteases and toxins from animal pathogens. The multi-gene family necessary
for secretion of these enzymes is now known as the type II system or the main
terminal branch (MTB) of the general secretion pathway (GSP). As summarized by
Pugsley et al. (1997), the current tally includes type II systems from Klebsiella
oxytoca (pul), Erwinia chrysanthemi and carotovora (out), Xanthomonas campestris
(xps), Pseudomonas aeruginosa (xcp), Aeromonas hydrophila (exe), and Vibrio
cholerae (eps). A second type II system (sps) necessary for deposition of the S
layer on the cell surface in A. hydrophila is more similar to the X. campestris
than A. hydrophila genes (Thomas & Trust, 1995). The biggest surprise has been
the discovery of a complete set of type II secretion genes in E. coli K12. The E.
coli genes are not expressed under normal growth conditions, and a search is
underway to find inducing conditions and secretion substrates (Francetic &
Pugsley, 1996). Impressive progress has already been made in defining components
of the pathway. What remains to be understood in mechanistic detail is how this
protein secretion system functions.
PMID- 9641974
TI - Graded expression of Emx-2 in the adult newt limb and its corresponding
regeneration blastema.
AB - Amputation of a newt limb causes stump cells to organize the reformation of the
missing structures. The phenomenon is remarkably precise in that the regeneration
is perfect. During the first few days following amputation, the tissue proximal
to the plane of amputation gives rise to the blastema, an area of growth composed
of mesenchymal cells covered by a single epithelium. The blastema possesses a
morphogenetic potential characteristic of the structures that have been
amputated. Looking for control genes putatively involved in regeneration, we
cloned the newt version of the mouse and human Emx-2. Its expression is
restricted to the skin of the regeneration territories and is graded along the
proximal-distal axis of both forelimb and hindlimb, with higher levels in distal
regions. The regeneration blastema also show this proximal-distal graded level of
expression with distal blastemas (mid-radius and ulna) showing higher levels of
expression when compared to blastemas of more proximal origin (mid-humerus).
Finally, retinoic acid proximalizes both the level of Emx-2 expression and the
positional memory of the blastema suggesting Emx-2 may participate in pattern
formation by specifying positional information.
PMID- 9641975
TI - Recognition of core-type DNA sites by lambda integrase.
AB - Escherichia coli phage lambda integrase (Int) is a 40 kilodalton, 356 amino acid
residue protein, which belongs to the lambda Int family of site-specific
recombinases. The amino-terminal domain (residues 1 to 64) of Int binds to "arm
type" DNA sites, distant from the sites of DNA cleavage. The carboxy-terminal
fragment, termed C65 (residues 65 to 356), binds "core-type" DNA sites and
catalyzes cleavage and ligation at these sites. It has been further divided into
two smaller domains, encompassing residues 65 to 169 and 170 to 356,
respectively. The latter has been characterized and its crystal structure has
been determined. Although this domain catalyzes the cleavage and rejoining of DNA
strands it, unexpectedly, does not form electrophorectically stable complexes
with core-type DNA. Here we have investigated the critical features of lambda Int
binding to core-type DNA sites; especially, the role of the central 65 to 169
domain. To eliminate the complexities arising from lambda Int's heterobivalency
we studied Int C65, which was shown to be as competent as Int, in binding to, and
cleaving, core-type sites. Zero-length UV crosslinking was used to show that
Ala125 and Ala126 make close contact with bases in the core-type DNA.
Modification by pyridoxal 5'-phosphate was used to identify Lys103 at the protein
DNA interface. Since both of the identified loci are in the central domain, it
was cloned and purified and found to bind to core-type DNA autonomously and
specifically. The synergistic roles of the catalytic and the central, or core
binding (CB), domains in the interaction with core-type DNA are discussed for
(Int and related DNA recombinases.
PMID- 9641976
TI - Perturbation of nucleosome structure by the erythroid transcription factor GATA
1.
AB - The ability of transcription factors to gain access to their sites in chromatin
requires the disruption or displacement of nucleosomes covering the promoter,
signalled by the generation of a nuclease hypersensitive site. We characterise
here the alterations in nucleosome structure caused by binding of the erythroid
factor GATA-1 to a nucleosome carrying GATA-1 sites. DNase I and micrococcal
nuclease probes show that GATA-1 binding causes extensive, cooperative breakage
of the histone/DNA contacts to generate a complex very similar to that formed by
the factor with free DNA. The only region which differs is confined to about 50
bp surrounding the nucleosome dyad axis which appears to be the domain of
residual contact between the DNA and histone octamer. Despite considerable
breakage of the histone/DNA contacts, the complex is completely stable in
solution, and disruption of the nucleosome is entirely reversible: it is
regenerated quantitatively upon removal of the transcription factor. Moreover,
the histone 2A/2B component of the octamer does not exchange to external
competitor. We suggest that formation of this complex may be a step in the
generation of a fully hypersensitive site in vivo over regulatory elements
containing GATA family binding sites.
PMID- 9641977
TI - Non-nearest neighbor effects on the thermodynamics of unfolding of a model mRNA
pseudoknot.
AB - The upstream autoregulatory mRNA leader sequence of gene 32 of 17 T-even and
related bacteriophages folds into a simple tertiary structural motif, a hairpin
type RNA pseudoknot. In phage T4, the pseudoknot is contained within 28
contiguous nucleotides which adopt a pseudocontinuous helical structure derived
from two coaxially stacked helical stems of four (stem 1) and seven (stem 2) base
pairs connected by two inequivalent single-stranded loops of five and one
nucleotide(s). These two loops cross the minor and major grooves of stems 1 and
2, respectively. In this study, the equilibrium unfolding pathway of a 35
nucleotide RNA fragment corresponding to the wild-type and sequence variants of
the T4 gene 32 mRNA has been determined through analysis of dual-wave-length,
equilibrium thermal melting profiles via application of a van't Hoff model based
on multiple sequential, two-state transitions. The melting profile of the wild
type RNA is well-described by two sequential melting transitions over a wide
range of magnesium concentration. Compensatory base-pair substitutions
incorporated into helical stems 1 and 2 were used to assign the first low
enthalpy, moderate tm melting transition to the denaturation of the short three
to four base-pair stem 1, followed by unfolding of the larger seven base-pair
stem 2. We find that loop 1 substitution mutants (A10 to G10, C10, U10 or GA10)
strikingly uncouple the melting of stems 1 and 2, with the U10 substitution and
the GA10 loop expansion more destabilizing than the G10 and C10 substitutions. A
significant increase in the extent of cleavage by RNase T1 following the
conserved G26 (the 3' nucleotide in loop 2) in the U10, G10, and GA10 mutants
suggests that an altered helix-helix junction region in this mutant may be
responsible, at least in part, for this uncoupling. In addition to a modest
destabilization of stem 2, the major effect of deletion or nucleotide
substitution in the 3' single-stranded tail is a destabilization of stem 1, a non
nearest neighbor tertiary structural effect, which may well be transmitted
through an altered loop 1-core helix interaction. In contrast, truncation of the
5' tail has no effect on the stability of the molecule.
PMID- 9641978
TI - Combinatorial selection of a small RNA that induces amplification of IncFII
plasmids in Escherichia coli.
AB - Cellular RNAs play fundamental roles as genetic messages, structural components
and, in some cases, as catalytic agents. The ability to create vast combinatorial
libraries of random RNA sequences has previously been exploited in vitro to
identify RNA aptamers with desirable binding specificities, and to isolate RNAs
with novel catalytic properties. Despite the advantages of in vitro selections
from RNA libraries, there is no way to predict if the identified RNAs can
function in living cells. We are therefore exploring random RNA expression
libraries in Escherichia coli to search for small RNAs with novel functions. Here
we describe selections that identified a small RNA (approximately 260
nucleotides) capable of altering the copy-number control circuitry of IncFII
plasmids. The novel RNA appears to function by annealing to a region of the mRNA
encoding the plasmid replicator protein. The resulting RNA-RNA hybrid permits
translation of the replicator protein, but blocks base-pairing with a natural
negative regulatory RNA. Implications of this in vivo selection strategy are
discussed.
PMID- 9641979
TI - A nickel complex cleaves uridine in folded RNA structures: application to E. coli
tmRNA and related engineered molecules.
AB - To gain more insight about Escherichia coli tmRNA structure, NiCR, a square
planar macrocyclic nickel (II) complex, was used to probe guanine N7 exposure. On
the basis of this additional structural information, a refined secondary
structure of the molecule is proposed. In addition to its known specificity for
guanine N7, we show here that the chemical probe can also cleave at specific
uridine residues. In contrast to the alkaline-labile modification of guanine, the
reactivity of NiCR at these uridine residues results in direct strand scission.
To better characterize the uridine cleavage sites and assess the importance of
the RNA structure for the reaction to occur, smaller RNA molecules derived from
one pseudoknot (PK4) of E. coli tmRNA containing two uridine cleavage sites were
engineered and probed. It is shown that this pseudoknot can fold by itself in
solution and that the expected uridine residues are also cleaved by the nickel
complex, suggesting that only a local sequence and/or structural context is
required for cleavage. In E. coli tmRNA, the five uridine cleavage sites are
located in double-stranded regions. These sites contain a G-U wobble base-pair
and a downstream uridine which is cleaved. Using smaller RNAs derived from one
stem of PK4, systematic changes in the proposed recognition motif indicate that
the G-U pair is required for cleavage. Furthermore, there is no cleavage if the G
U pair is reversed. If the recognition motif is moved within the stem, the
cleavage site moves accordingly. Additionally, if the recognition motif is
changed such that the G-U pair is flanked by two uridine residues, the reactivity
occurs only at the 3' uridine. Radical quenching studies have indicated that
sulfate radical, as in the case of guanine oxidation, is involved in uridine
oxidation. Although additional studies are required to better characterize the
reaction, this paper reports a novel specificity for a chemical probe which may
be useful for investigating structural motifs involving G-U pairs in folded RNAs.
PMID- 9641980
TI - Epitopes fused to F-pilin are incorporated into functional recombinant pili.
AB - In order to develop a system which allows infection by an epitope-specific phage
antibody via an F-pilus expressing that epitope, a study on the expression of
foreign sequences on F-pilin was undertaken. Initially, a plasmid library was
constructed with random sequences encoding one to five amino acid residues fused
to the C terminus of F-pilin (traA) which was used to complement an F-plasmid
with an amber mutation in traA. Functional F-pilin fusions were detected using
the filamentous phage, fUSE2, which transduces tetracycline resistance, as well
as immunoblots using a monoclonal antiserum specific for the acetylated N
terminus of pilin. All the clones selected expressed the pilin-fusions and
displayed full sensitivity towards fUSE2 infection, which was indistinguishable
from the wild-type F-pilin. The sequences of fUSE2-sensitive clones when compared
to randomly selected clones which were not fUSE2-sensitive, revealed no obvious
pattern in the amino acid residues fused to the C terminus, except for a
preference for a hydrophilic amino acid at position +1. Mutating the C-terminal
Leu in wt (wild-type) pilin to Ser blocked pilus assembly and fUSE2 infection;
the pilin was correctly processed but the level of acetylation at the N terminus
appeared to decrease. Fusing a known epitope (myc) directly to the C terminus
blocked processing of F-pilin leading to loss of F-pilus assembly and function.
The introduction of random sequences between traA and this epitope yielded fully
recombinant, functional F-pili but this appeared to be due to processing of the
extension by an unidentified protease leading to loss of the epitope. Surface
expression of another epitope (G2-10) was clearly demonstrated by immuno-electron
microscopy of pili with a G2-10 monoclonal antibody. A different five amino acid
residue spacer between the F-pilin C terminus and the G2-10 epitope produced a
system that was transfer-proficient and fUSE2-sensitive, but the pili were barely
detectable by immunoblots or by electron microscopy. While the underlying rules
that govern successful epitope expression at the C terminus of F-pilin remain
elusive, many types of foreign sequences can be displayed with varying degrees of
success. Our results also suggest that pilin sequence determines a number of
steps in the complex pathway for pilus assembly.
PMID- 9641981
TI - Identification of protein-protein interactions of the major sperm protein (MSP)
of Caenorhabditis elegans.
AB - In nematodes, sperm are amoeboid cells that crawl via an extended pseudopod.
Unlike those in other crawling cells, this pseudopod contains little or no actin;
instead, it utilizes the major sperm protein (MSP). In vivo and in vitro studies
of Ascaris suum MSP have demonstrated that motility occurs via the regulated
assembly and disassembly of MSP filaments. Filaments composed of MSP dimers are
thought to provide the motive force. We have employed the yeast two-hybrid system
to investigate MSP-MSP interactions and provide insights into the process of MSP
filament formation. Fusions of the Caenorhabditis elegans msp-142 gene to both
the lexA DNA binding domain (LEXA-MSP) and a transcriptional activation domain
(AD-MSP) interact to drive expression of a lacZ reporter construct. A library of
AD-MSP mutants was generated via mutagenic PCR and screened for clones that fail
to interact with LEXA-MSP. Single missense mutations were identified and mapped
to the crystal structure of A. suum MSP. Two classes of mutations predicted from
the structure were recovered: changes in residues critical for the overall fold
of the protein, and changes in residues in the dimerization interface. Multiple
additional mutations were obtained in the two carboxy-terminal beta strands, a
region not predicted to be involved in protein folding or dimer formation. Size
fractionation of bacterially expressed MSPs indicates that mutations in this
region do not abolish dimer formation. A number of compensating mutations that
restore the interaction also map to this region. The data suggest that the
carboxy-terminal beta strands are directly involved in interactions required for
MSP filament assembly.
PMID- 9641982
TI - A general module for RNA crystallization.
AB - Crystallization of RNA molecules other than simple oligonucleotide duplexes
remains a challenging step in structure determination by X-ray crystallography.
Subjecting biochemically, covalently and conformationally homogeneous target
molecules to an exhaustive array of crystallization conditions is often
insufficient to yield crystals large enough for X-ray data collection. Even when
large RNA crystals are obtained, they often do not diffract X-rays to resolutions
that would lead to biochemically informative structures. We reasoned that a well
folded RNA molecule would typically present a largely undifferentiated molecular
surface dominated by the phosphate backbone. During crystal nucleation and
growth, this might result in neighboring molecules packing subtly out of
register, leading to premature crystal growth cessation and disorder. To overcome
this problem, we have developed a crystallization module consisting of a normally
intramolecular RNA-RNA interaction that is recruited to make an intermolecular
crystal contact. The target RNA molecule is engineered to contain this module at
sites that do not affect biochemical activity. The presence of the
crystallization module appears to drive crystal growth, in the course of which
other, non-designed contacts are made. We have employed the GAAA
tetraloop/tetraloop receptor interaction successfully to crystallize numerous
group II intron domain 5-domain 6, and hepatitis delta virus (HDV) ribozyme RNA
constructs. The use of the module allows facile growth of large crystals, making
it practical to screen a large number of crystal forms for favorable diffraction
properties. The method has led to group II intron domain crystals that diffract X
radiation to 3.5 A resolution.
PMID- 9641983
TI - Dynamical behavior of the HIV-1 nucleocapsid protein.
AB - The HIV-1 nucleocapsid protein (NC) contains two CCHC-type zinc knuckle domains
that are essential for genome recognition, packaging and infectivity. The
solution structure of the protein has been determined independently by three
groups. Although the structures of the individual zinc knuckle domains are
similar, two of the studies indicated that the knuckles behave as independently
folded, non-interacting domains connected by a flexible tether, whereas one study
revealed the presence of interknuckle NOE cross-peaks, which were interpreted in
terms of a more compact structure in which the knuckles are in close proximity.
We have collected multidimensional NMR data for the recombinant, isotopically
labeled HIV-1 NC protein, and confirmed the presence of weak interknuckle NOEs.
However, the NOE data are not consistent with a single protein conformation. 15N
NMR relaxation studies reveal that the two zinc knuckle domains possess different
effective rotational correlation times, indicating that the knuckles are not
tumbling as a single globular domain. In addition, the 1H NMR chemical shifts of
isolated zinc knuckle peptides are very similar to those of the intact protein.
The combined results indicate that the interknuckle interactions, which involve
the close approach of the side-chains of Phe16 and Trp37, are transitory. The
solution behavior of NC may be best considered as a rapid equilibrium between
conformations with weakly interacting and non-interacting knuckle domains. This
inherent conformational flexibility may be functionally important, enabling
adaptive binding of NC to different recognition elements within the HIV-1 psi-RNA
packaging signal.
PMID- 9641984
TI - Multiple open forms of ribose-binding protein trace the path of its
conformational change.
AB - Conformational changes are necessary for the function of bacterial periplasmic
receptors in chemotaxis and transport. Such changes allow entry and exit of
ligand, and enable the correct interaction of the ligand-bound proteins with the
membrane components of each system. Three open, ligand-free forms of the
Escherichia coli ribose-binding protein were observed here by X-ray
crystallographic studies. They are opened by 43 degrees, 50 degrees and 64
degrees with respect to the ligand-bound protein reported previously. The three
open forms are not distinct, but show a clear relationship to each other. All are
the product of a similar opening motion, and are stabilized by a new, almost
identical packing interface between the domains. The changes are generated by
similar bond rotations, although some differences in the three hinge segments are
needed to accommodate the various structural scenarios. Some local repacking also
occurs as interdomain contacts are lost. The least open (43 degrees) form is
probably the dominant one in solution under normal conditions, although a mixture
of species seems likely. The open and closed forms have distinct surfaces in the
regions known to be important in chemotaxis and transport, which will
differentiate their interactions with the membrane components. It seems certain
that the conformational path that links the forms described here is that followed
during ligand retrieval, and in ligand release into the membrane-bound permease
system.
PMID- 9641985
TI - Role of main-chain electrostatics, hydrophobic effect and side-chain
conformational entropy in determining the secondary structure of proteins.
AB - The physiochemical bases of amino acid preferences for alpha-helical, beta
strand, and other main-chain conformational states in proteins is controversial.
Hydrophobic effect, side-chain conformational entropy, steric factors, and main
chain electrostatic interactions have all been advanced as the dominant physical
factors which determine these preferences. Many attempts to resolve the
controversy have focused on small model systems. The disadvantage of such systems
is that the amino acids in small molecules are largely exposed to the solvent. In
proteins, however, the amino acids are in contact with the solvent to a different
degree, causing a large variability of strengths of all interactions. The
estimates of mean strengths of interactions in the actual protein environment are
therefore essential to resolve the controversy. In this work the experimental
protein structures are used to estimate the mean strengths of various
interactions in proteins. The free energy contributions of the interactions are
implemented into the Lifson-Roig theory to calculate the helix and strand free
energy profiles. From the profiles the secondary structures of proteins and
peptides are predicted using simple rules. The role of hydrophobic effect, side
chain conformational entropy, and main-chain electrostatic interactions in
determining the secondary structure of proteins is assessed from the abilities of
different models, describing stability of secondary structures, to correctly
predict alpha-helices, beta-strands and coil in 130 proteins. The three-state
accuracy of the model, which contains only the free energy terms due to the main
chain electrostatics with 40 coefficients, is 68.7%. This accuracy is approaching
to the accuracy of currently the best secondary structure prediction algorithm
based on neural networks (72%); however, many thousands of parameters have to be
optimized during the training of the neural networks to reach this level of
accuracy. The correlation coefficient between the calculated and the experimental
helix contents of 37 alanine based peptides is 0.91. If the hydrophobic and the
side-chain conformational entropy terms are included into the helix-coil
transition parameters, the accuracy of the algorithm does not improve
significantly. However, if the main-chain electrostatic interactions are excluded
from the helix-coil and strand-coil transition parameters, the accuracy of the
algorithm reaches only 59.5%. These results support the dominant role of the
short-range main-chain electrostatics in determining the secondary structure of
proteins and peptides. The role of the hydrophobic effect and the side-chain
conformational entropy is small.
PMID- 9641986
TI - Behavioural and hormonal responses of the pied flycatcher to environmental
stressors.
AB - I investigated the effects of high plasma levels of corticosterone in male pied
flycatchers, Ficedula hypoleuca, during the period of territorial establishment
and the nestling period. In a second experiment males were exposed to a
territorial intruder, a great spotted woodpecker model and a weasel model during
the nest-building and nestling periods and their behavioural and hormonal
reactions studied. Males were also exposed to handling stress (hormonal study)
during these periods. During the period of territorial establishment,
corticosterone-treated males, as well as control males, abandoned the territory
in which they were captured; however, males in both groups very soon established
new territories. During the nestling period, corticosterone-treated males, but
not control males, abandoned their nests. During the nest-building period, intact
males frequently attacked the territorial intruder but corticosterone-treated
males never did; the woodpecker was only rarely attacked by intact males, and the
weasel never. During the nestling period, the weasel was not attacked and
territorial intruders only rarely; but woodpeckers were frequently attacked. With
the progress of the breeding season, male flycatchers significantly reduced their
sensitivity, in terms of the adrenocortical response, to all stressors tested.
During the nest-building period, corticosterone levels were significantly higher
in males exposed to handling, a weasel and a territorial intruder than in
unmanipulated males; corticosterone levels in males exposed to a woodpecker did
not differ from those in unmanipulated males; and testosterone levels were
significantly elevated in males exposed to a woodpecker and to an intruder, but
were reduced in males exposed to a weasel. Handling did not affect the
testosterone level. During the nestling period, all groups showed low
testosterone levels, and only exposure to a weasel and to handling increased
corticosterone levels significantly. The results indicate that environmentally
induced changes in testosterone and corticosterone secretion can be affected
independently from one another, and that there are ecological bases for the
differentiated hormonal responses to stress. Copyright 1998 The Association for
the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
Animal Behaviour.
PMID- 9641987
TI - Mate guarding and risk assessment by male mountain baboons during inter-troop
encounters.
AB - Aggressive herding of females is a frequent but not invariant response by male
savannah baboons, Papio cynocephalus, to encounters with other troops. While
males in some troops are consistently more likely to herd than those in others,
not all inter-troop encounters result in herding, even within particular troops.
This suggests that males assess the risk of male invasion posed by each encounter
and respond accordingly. We used data from baboon troops in the Drakensberg
mountains to determine the rules males follow in deciding whether to herd.
Consistent differences between troops were explained only by the adult sex ratio.
Males were more likely to herd if the sex ratio of their own troop was female
biased, a finding that is concordant with the observation that males are more
likely to immigrate into troops where the sex ratio is more female biased than
the population average. Differences within troops were a consequence only of
encounter distance, with herding being more likely at closer distances. We found
a negative correlation between the angle of approach to the other troop and the
subsequent angle of deflection. We interpret this to mean that herding functions
to increase the distance between the interacting troops, thereby curtailing
opportunities for strange males to inspect the troop and determine its sex ratio.
In this way, possibly unlike those in other populations, the decision rules of
these male baboons are geared to protecting longer-term reproductive prospects.
Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1997
The Association for the Study of Animal Behaviour.
PMID- 9641988
TI - Interactions between cleaning gobies and territorial damselfish on coral reefs.
AB - We studied the interactions between cleaning gobies, Elacatinus spp., at cleaning
stations and territorial dusky damselfish, Stegastes fuscus, on a Barbadian
fringing reef to enhance our understanding of the behavioural impact of cleaning
stations on members of a coral reef community. Cleaning stations within
damselfish territories were visited by significantly fewer species and fewer
individuals than those outside damselfish territories. At cleaning stations
within damselfish territories, the main client was the territory holder itself.
Client behaviour did not differ between the two types of cleaning station;
however, cleaning gobies at stations within damselfish territories spent less
time cleaning clients, their cleaning bouts were shorter, and their feeding rate
on clients was slower. These effects appear to be due to the repeated aggression
of territorial damselfish towards fish intruding on to their territories to visit
cleaning stations. The overlap between a territorial damselfish and a cleaning
station therefore appears to have detrimental impacts on cleaning goby foraging.
The presence of cleaning stations within damselfish territories exerted some
effects on the territory owners. Although the rates of intrusions were similar on
territories with and without cleaning stations, damselfish with cleaning stations
tended to chase intruders more often, had a lower foraging rate, and were at
higher risk of egg predation because of increased intrusions by egg predators. A
potential benefit to territorial damselfish is regular access to a cleaning
station; however, the magnitude of this benefit is unknown. This study reveals
that damselfish, which are ubiquitous on coral reefs, can generate significant
variation in levels of use of cleaning stations, which leads to new questions
relating to the settlement behaviour of both cleaning gobies and damselfish.
Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
The Association for the Study of Animal Behaviour.
PMID- 9641989
TI - Direct homing behaviour in the ant Tetramorium caespitum (Formicidae,
Myrmicinae).
AB - Direct homing refers to the behaviour whereby an ant with food runs in an almost
straight line to the nest. We determined whether non-polarized light acts as a
directional cue in the direct homing behaviour of the grass ant, Tetramorium
caespitum. We carried out tests (1) under a blue sky or in total overcast
conditions in the field, and (2) with a view of the sun or with a non-polarized
light within a box in the laboratory. The ants' paths were recorded, and then
analysed by means of circular and linear statistics. Ant workers with food were
able to home directly under a blue sky, under totally overcast skies, and even
under non-polarized lighting. In a fifth test we displaced the ants at the
beginning of the homing trip; they returned to the presumed nest location along a
path that ran parallel to the true homing vector, as if they had not been
displaced. The results suggest that the ants home by dead reckoning, that is,
they can measure directional changes and distances travelled during the outward
trip, and integrate them into a mean home vector for direct homing depending on
an external light-based reference system, that is, either the polarized skylight
pattern or non-polarized lighting. Copyright 1998 The Association for the Study
of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
Behaviour.
PMID- 9641990
TI - Adopting adoption.
AB - The common occurrence of adoption among birds and mammals presents evolutionary
biologists with an explanatory challenge. The benefits to adoptees are self
evident, but the benefits to the adopter(s), the origin of the set of behaviours
that constitute 'adoptive' behaviour, and the conditions for its spread in
populations are not always clear. Explanations in terms of direct and indirect
benefits to adopters and adoptees, and in terms of conflict between them have
been suggested to account for the current functions and the evolutionary origin
of 'adoptive' behaviour. In this paper we emphasize one aspect of the parenting
behaviour associated with adoption that has been neglected: we suggest that
adoption in birds and mammals is a route for the transfer of learnt information
through social learning of patterns of behaviour, including styles of parenting.
By using simple models we show that learning parenting from non-parents may
provide additional opportunities for the spread of the 'adoptive' behaviour
itself, even when it has no selective advantage. We also offer an additional
explanation for the adaptive significance of adoption for both adopters and
adoptees. Our 'match-making' hypothesis suggests that in some cases, by adopting
foreign young, parents provide their genetic young with future ecologically
compatible, but genetically unrelated, mates. Copyright 1998 The Association for
the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
Animal Behaviour.
PMID- 9641991
TI - How mixed-species foraging flocks develop in response to benefits from
observational learning.
AB - We created experimental situations where observers (great tit, Parus major and
marsh tit, P. palustris) acquired one of five types of experience near
conspecific and non-conspecific demonstrators: (1) neither demonstrator was
feeding; (2) only the conspecific was feeding; (3) only the non-conspecific was
feeding; (4) both were feeding and the observer received a reinforcement (food)
near the conspecific; and (5) as (4), but the reinforcement was given near the
non-conspecific. After each treatment, we recorded whether the observer
approached a caged conspecific or a caged non-conspecific. There was a baseline
preference for approaching conspecifics but this could be overcome by learnt
associations so that the birds would then approach non-conspecifics. When there
was an opportunity to distinguish between successful and unsuccessful foragers
(demonstrators), and the successful forager was not conspecific, observers of the
dominant species approached the successful subordinate non-conspecifics.
Observers of the subordinate species approached the dominant species only if they
had received a food reinforcement near them. Observers followed non-conspecific
individuals more often at temperatures below than above 0 degreesC and chose a
conspecific individual more often above than below 0 degreesC. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9641992
TI - Singing and mating success in water pipits: one specific song element makes all
the difference.
AB - Positive correlations between male vocalization and reproductive success have
been documented for many animal species. They are usually based on differences
between males in vocalization rate, duration or repertoire size. Here, we present
probably the first field study linking differences in territorial overlap and
mating status to differences in a single, clearly definable song element, the
'Snarr'. Male water pipits, Anthus spinoletta, with high Snarr scores were mated
more often than males with low scores, and their territories overlapped less with
those of neighbours. Although correlating positively with male body condition,
the frequency of the Snarr did not reflect male age, territory size, territory
quality in terms of food and paternal performance. Therefore, it seems unlikely
that the higher mating success of males with high Snarr scores results from
active female choice of high-quality males; rather, high Snarr scores seem to
signal dominance in males. Likely mechanisms that produce the link between
vocalization and mating success, and potential costs that prevent some males from
producing the Snarr at a higher rate, are discussed. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9641993
TI - High population density in bank voles stimulates food hoarding after breeding.
AB - The effects of conspecific density (i.e. risk of intraspecific competition) on
hoarding behaviour were studied in breeding pairs of bank voles, Clethrionomys
glareolus. I simulated high population density by using odours of conspecifics,
to exclude the direct effects of exploitation or interference competition for
food. The pairs of bank voles hoarded only at the end of their breeding season.
Hoarding was not correlated with whether the voles had a litter during the
experiment or their litter size, but was more likely at the high population
density and for pairs with small females. This may indicate that smaller females
especially make caches in the autumn, possibly to ensure better winter survival
under high population density. I discuss the hoarding behaviour of bank voles in
relation to their territorial behaviour and food resources during the breeding
season and predictable population changes during winter. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9641994
TI - Statistical models of transitive and intransitive dominance structures.
AB - We present an approach based on generalized linear models for analysing dominance
data. First, dominance is defined as a parameter characterizing the relationship
between two individuals, determining the expected number of successes of the
first individual in disputes with the other. Second, models known from the
literature of two different forms of transitivity are defined in terms of these
parameters, and examples of different tests of these models are given. Third, a
new model is developed where the traits of individuals involved in the dominance
interactions are included as covariates. Finally, we show how two forms of
intransitive models of dominance structures can be constructed by including a
certain interaction term between the trait variables, and terms taking into
account the effect of relatedness between the individuals in the group. We
reanalyse several data sets in the literature, and also discuss Appleby's method
(1983, Anim. Behav., 31, 600-608), which is frequently used in analysis of
dominance data. Copyright 1998 The Association for the Study of Animal Behaviour.
Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9641995
TI - Male potential reproductive rate influences mate choice in a bushcricket.
AB - Male bushcrickets, Requena verticalis, provide their mates with a proteinaceous
nuptial gift, which functions both as paternal investment in offspring and to
ensure sperm transfer. When nutrients are limited, males have a lower potential
reproductive rate than females, so the operational sex ratio becomes female
biased. Males are then expected to discriminate more in their choice of mate for
two reasons: (1) the relatively higher female potential reproductive rate should
reduce the costs of rejecting a female; (2) multiple mating by females should
increase variance in female mate quality, because of first male sperm precedence.
Males are known to discriminate against old females, which are more likely to
have mated previously. Our objective in this study was to partition
experimentally the influences of male potential reproductive rate (manipulated by
diet) and variance in female quality (estimated by age) and to assess their
relative influence on the level of mate choice of male bushcrickets. The
potential reproductive rate of males had a great impact on their choosiness,
whereas variance in female age had no effect. These results support recent
theoretical models that predict costs, rather than benefits, will primarily
influence the level of mate choice. Copyright 1998 The Association for the Study
of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
Behaviour.
PMID- 9641996
TI - Male parental care, differential parental investment by females and sexual
selection.
AB - Males play a variable parental role in reproduction, ranging from no male
parental care to extensive male care. Females may acquire either direct or
indirect fitness benefits from their mate choice, and direct fitness benefits
include male parental care. Theoreticians have traditionally emphasized direct
fitness benefits to females in species with extensive male parental care. We
review the literature and show extensive variation in the patterns of male care,
related to the attractiveness of males to females. At one extreme of this
continuum, females invest differentially in parental care, investing more when
paired with attractive males. The costs of female parental care and other aspects
of parental investment may be balanced by benefits in terms of more attractive
sons and/or more viable offspring. At the other extreme, in species with
extensive direct fitness benefits, males with preferred sexual phenotypes provide
the largest relative share of parental care. A comparative study of birds
revealed that the extent of the differential female parental investment was
directly related to the frequency of extra-pair paternity. Since extra-pair
paternity may arise mainly as a consequence of female choice for indirect fitness
benefits, this result supports our prediction that differential parental
investment is prevalent in species where females benefit indirectly from their
mate choice. The consequences for sexual selection theory of these patterns of
male care in relation to male attractiveness are emphasized. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9641997
TI - Tibial coloration, fluctuating asymmetry and female choice behaviour in the
damselfly Platycypha caligata.
AB - The territorial damselfly Platycypha caligata (Odontata: Chlorocyphidae) has a
courtship behaviour where males wave the white anterior surface of all six
laterally enlarged tibiae at females. I experimentally altered this white tibial
surface using black paint to determine the effect on male behaviour of a 25%
reduction in area, or an increase in asymmetry between the left and right side of
the body. I collected behavioural data on courtship, mating and fighting for
males already holding territories. Neither a reduction in the area nor an
increase in asymmetry of tibial whiteness affected male mating rate, courtship
rate or fighting behaviour. These manipulations also had no significant effect on
the daily presence at the study site. Males whose tibial whiteness was
experimentally removed also showed no decrease in mating rate or change in
fighting behaviour while territorial. The complete removal of tibial whiteness
did, however, lead to a significant reduction in daily presence, possibly due to
a reduced ability to acquire or hold a territory. There was no relationship
between natural levels of asymmetry in tibial whiteness and mating rate, courting
rate or fighting behaviour for males with territories. However, the natural area
of tibial whiteness was significantly positively related to both mean male mating
rate and copulation duration for territorial males. This result suggests that a
phenotypic correlate of area of tibial whiteness, probably body size, is sexually
selected through female choice among males that already hold
territories.Copyright 1998 The Association for the Study of Animal Behaviour.
Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9641998
TI - Beaver response to recurrent alien scents: scent fence or scent match?
AB - By repeatedly presenting an alien scent to territory-owning beavers, Castor
canadensis, we tested two competing hypotheses about the function of scent
marking: scent fence and scent matching. The scent-fence hypothesis predicts that
territory owners should respond increasingly strongly over time towards a
recurrent alien scent because of the ineffectiveness of previous responses. The
scent-matching hypothesis predicts that the intensity of response should be the
same or decrease because, without the presence of the intruding signaller coupled
with the chemical signal, the presence of the scent itself does not advertise the
ownership of a territory. The response level of resident beaver families was
stable to strangers' anal gland secretions (AGSs) and decreased to strangers'
castoreum during a period of 6 days. These results support the scent-matching
hypothesis but not the scent-fence hypothesis. Copyright 1998 The Association for
the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
Animal Behaviour.
PMID- 9641999
TI - Song learning in brood-parasitic indigobirds Vidua chalybeata: song mimicry of
the host species.
AB - Brood-parasitic village indigobirds, Vidua chalybeata, were bred in captivity and
foster-reared by their normal host, red-billed firefinch, Lagonosticta senegala,
or by an experimental foster species, Bengalese finch, Lonchura striata. Male
indigobirds reared by Bengalese finches developed the songs of Bengalese finches,
and males reared by firefinches developed songs of firefinches. Males copied
their foster father only when they had lived with him long after independence (45
days post-fledging), while males separated normally at independence (22-24 days
post-fledging) copied songs of other individuals and not songs of their foster
father. Males reared by Bengalese finches showed no preference to learn firefinch
song over songs of the experimental foster species or other control finch species
even when they had lived with firefinches as companions from the time of fledging
to independence. Males copied several song themes, acquired the same number of
mimicry songs, and acquired their songs at the same age, whether reared by
Bengalese finches or by firefinches. When they lived with other indigobirds, the
male indigobirds copied mimicry songs of male indigobirds that mimicked the same
foster species. We predicted mimicry-song specificity and repertoire size in
experimental indigobirds from a hypothesis of an early developmental period when
young indigobirds focus their attention on their foster parents, and a later
period when they direct their attention to other birds with similar songs. The
predictions, based on field observations of wild birds, were that (1) males
reared by a novel foster species other than the normal host would learn the song
of that foster species, and (2) males that left their foster parents at the
normal time of independence would copy the songs of other individuals, including
other adult indigobirds that mimicked the same foster species. Begging calls of
young indigobirds did not mimic the calls of young firefinches. Indigobirds
reared alone, or with young of the normal host or of the experimental foster
species, all developed begging calls in adult song that resembled their own
begging as nestlings and fledglings, and only males that heard other adult
indigobirds with firefinch-mimicry begging developed firefinch begging in their
song. The incorporation of the innate begging calls as well as the learned
begging calls into adult song, and the modification of the song themes of their
individual song models, suggest that song development involves processes in
addition to copying the songs of their own foster species and of older adult male
indigobirds with songs like their own foster parents. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9642000
TI - How mothers influence the development of litter-mate preferences in Belding's
ground squirrels.
AB - We performed three experiments to examine the role of mothers in the development
of litter-mate preferences in captive juvenile Belding's ground squirrels,
Spermophilus beldingi. First, when observed in the absence of mothers, juveniles
did not play preferentially with litter-mates, which suggests that mothers
somehow influence the ontogeny of litter-mate preferences. Second, when mothers
were present but unable to intervene in social interactions, juveniles displayed
litter-mate preferences, which suggests that mothers do not influence their
offsprings' social development by directly intervening in social interactions. In
another group, mothers were removed daily, a few hours before nocturnal
immergence, and returned the following morning. Juveniles in this group did not
display litter-mate preferences and at night they occupied burrows with many more
non-litter-mates than litter-mates. These results suggest that associating with
non-litter-mates can compromise the development of litter-mate preferences, and
implies that mothers indirectly influence social development by affecting the
identities of sleeping partners. Third, newly emergent juveniles that interacted
only with litter-mates for 3 days in the absence of mothers subsequently
preferred litter-mates over non-litter-mates as play partners. This result
demonstrates that once litter-mate preferences are instilled, due in part to
social experiences during juveniles' initial days above-ground, the preferences
are expressed even in the absence of mothers. Collectively, the results
demonstrate that the presence of S. beldingi mothers is important to juvenile
social development, but that mothers do not actively direct the ontogeny of their
offsprings' social relationships. Copyright 1998 The Association for the Study of
Animal Behaviour. Copyright 1998 The Association for the Study of Animal
Behaviour.
PMID- 9642001
TI - Future value and patch choice in least chipmunks.
AB - Animals subsisting on non-renewing patches confront a unique valuation problem,
in which the objective value of a patch is inversely related to the amount
already harvested. We investigated whether the subjective patch valuations of
captive least chipmunks, Tamias minimus, reflected this environmental constraint
as they foraged for buried patches of seeds. On the day following partial
depletion of two patches, chipmunks spontaneously selected the least depleted
patch, despite having no direct information about its former or present value.
These findings held across experiments in which the order and extent of patch
depletion were under the forager's control or experimental control. The animals
consistently chose sites from which they had taken the fewest items, despite
experiencing no difference in relative capture rate, suggesting that they
discounted patch value on the basis of amount harvested or harvest time.
Furthermore, the animals refused to return to patches they had completely
depleted, and when induced to re-dig depleted patches by placing seeds above
them, the animals chose randomly despite a three-fold difference in the number of
items previously taken from each, suggesting that they disregarded rewards taken,
attending only to the amount remaining. Subsequent experiments showed that
chipmunks can take past reward history into account. When we refilled previously
depleted patches and induced chipmunks to re-dig and deplete them again, they
treated the patches as renewable types and represented their value in terms of
the amount removed, not the amount left. Thus, the assessment mechanism of least
chipmunks is facultative: they expect that patches will not replenish, but are
prepared for exceptions. Copyright 1998 The Association for the Study of Animal
Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9642002
TI - An abrupt transition in colony founding behaviour in the ant Messor pergandei.
AB - Transitions in behaviour across a continuous distribution of organisms can
provide valuable information on how variation in behaviour is maintained. We used
analyses developed for interspecific hybrid zones to examine geographic variation
in colony founding strategy in the desert seed-harvester ant, Messor pergandei.
Newly mated females initiate new colonies either alone (haplometrosis) or
cooperatively with other foundresses (pleometrosis). The incidence of these
founding strategies were surveyed across the species' range and found to occur in
geographically distinct regions joined by a narrow transition zone. Foundresses
collected from haplometrotic sites were more likely to display aggression and
found solitary nests than foundresses from pleometrotic sites, suggesting that
geographical variation in metrosis is due to genotypic divergence. Foundresses
from transitional sites were generally not aggressive and tended to co-found
nests in the laboratory, yet rarely formed associations in the field. Such an
abrupt shift in behaviour indicates that variation in colony founding strategy is
maintained by selection rather than the result of secondary contact of neutral
characters. Level of aggression displays a wider cline than founding strategy and
is likely under selection only when accompanied by active strategy preference.
Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
The Association for the Study of Animal Behaviour.
PMID- 9642003
TI - Geographical variation in agonistic behaviour in a ring species of salamander,
Ensatina eschscholtzii.
AB - Ensatina eschscholtzii is a plethodontid salamander with several geographical
races distributed in a ring-like series throughout the coastal mountains and
inland Sierra Nevada mountains of California. Populations of these salamanders
show genetic and morphological divergence, and in this study, we examined
divergence in overt aggressive, passive aggressive/exploratory, avoidance and
sensory behaviours in four populations. Two of the populations represent a zone
of secondary contact between coastal and inland lineages of Ensatina. We recorded
behaviour of resident salamanders paired with same-sex intruders during the non
courtship season. The residents' behaviour was affected independently by the
population of the resident and the population of the intruder but not by the
interaction between the resident population and the intruder population. Levels
of agonistic and sensory behaviour showed a high degree of constraint among the
populations. These behaviours also showed divergence among coastal and inland
populations, and the geographical variation in behaviour is consistent with the
phylogenetic history of Ensatina. Convergent evolution of behaviour appears to
have occurred at the zone of secondary contact between the coastal and inland
lineages. Variation in agonistic and sensory behaviour among the populations
observed and between the sexes suggests that there may be geographical and sexual
variation in territoriality or competition. Copyright 1998 The Association for
the Study of Animal Behaviour. Copyright 1999 The Association for the Study of
Animal Behaviour.
PMID- 9642004
TI - The energetic cost of begging behaviour in nestling house wrens.
AB - This study presents data relevant to the hypothesis that the energy expenditure
associated with begging influences the signalling of need by nestling birds. We
used open-circuit respirometry to measure the energy costs of resting, begging
and non-begging activities in nestling house wrens, Troglodytes aedon, ranging in
age from 1 to 11 days post-hatching. Across all ages, begging caused a 27%
increase in metabolism above resting rates. The metabolic rate during begging was
not related to begging vigour. However, more vigorous begs were longer and so
required a greater total energy expenditure. We analysed videotapes of broods for
nestling behavioural time budgets which were combined with the metabolic data and
data on growth at different ages to generate daily energy budgets. Over a 24-h
period, the cumulative energy allocated to begging was slight, ranging from 0.02%
of the energy budget in younger nestlings (3 days old) to 0.22% in older ones (10
days old). In contrast, non-begging movements accounted for 2 and 9% of the daily
energy budget of younger and older nestlings, respectively. Relative to daily
growth, the energy allocated to begging was equivalent to 0.05% (younger
nestlings) and 2.3% (older nestlings) of the energy sequestered in new tissue,
whereas the values for non-begging activities were 5.1 and 96.8%, respectively.
These results suggest that the energetic cost of begging is not likely to have a
substantial role in influencing communication of need by nestlings. Copyright
1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
Association for the Study of Animal Behaviour.
PMID- 9642005
TI - Stabilizing and directional preferences of female Hyla ebraccata for calls
differing in static properties.
AB - Female frogs of many species show preferences for calls with particular
properties. This study focuses on female preferences in Hyla ebraccata for
computer-synthesized calls that differ in pulse-repetition rate or dominant
frequency. Both of these call properties are static acoustic properties of
advertisement calls of H. ebraccata (within-male coefficient of variation <5%).
Females exerted directional selection on dominant frequency, preferring low
frequency calls (2960 Hz) to calls with the dominant frequency of the population
mean (3240 Hz). Because size is negatively correlated with dominant frequency,
female choice could explain size-biased mating success observed in natural
populations. Females also exerted stabilizing selection on pulse-repetition rate,
preferring calls with a pulse-repetition rate of the population mean (99 Hz) to
calls with a pulse-repetition rate that was twice as fast (200 Hz). The results
of this study show that female choice creates either directional or stabilizing
selection on static properties of calls. Copyright 1998 The Association for the
Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
Behaviour.
PMID- 9642006
TI - Sex recognition and mate choice by male western toads, Bufo boreas.
AB - In field-based choice experiments, we examined sex recognition and mate choice in
male western toads, Bufo boreas. When given a simultaneous choice between a male
and a female of equal size, males did not discriminate between the sexes and
attempted to amplex a male or a female with equal frequency. When a test male
clasped a stimulus male, the stimulus male uttered a release call that caused the
test male to release the stimulus male. Male-male amplexus never lasted more than
3 s, but male-female amplexus was tenacious and prolonged. Furthermore, males
discriminated between gravid females that differed in body size, choosing larger
gravid females over smaller ones, but they did not discriminate between gravid
females or non-gravid females of equal size. In choice tests that excluded
chemical cues, males jumped more frequently towards large females than small
ones. Given that females are significantly larger than males, selecting larger
individuals as potential mates increases the probability that males amplex with a
female. Copyright 1998 The Association for the Study of Animal Behaviour.
Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9642007
TI - Temporal manipulation of ejaculate components by newly fertilized Drosophila
melanogaster females.
AB - Observations of newly mated Drosophila melanogaster females suggest that females
control the times at which components of the ejaculate cause behavioural and
physiological changes characteristic of fertilized females. Females that were
assayed immediately after they mated elicited as much courtship as they did when
they were virgins, but were unreceptive to copulation. Within a few minutes of
when they disengaged from copulation, most females performed ovipositor
extrusion, which has been classified as a rejection behaviour, in response to
courting males or males that had previously performed courtship. Most females
that were assayed immediately after mating had already ovulated. The females,
however, do not begin to lay eggs until 4-6 h after mating, at which time they
elicit very little courtship (Scott & Richmond 1985, Anim. Behav., 33, 817-824).
Our observations suggest that neither ovipositor extrusion nor male-synthesized
pheromones that are transferred to females' cuticles during copulation inhibit
males' courtship of newly fertilized females. Thus, males cannot determine that
newly fertilized females are unreceptive to copulation. These observations also
indicate that the failure of newly fertilized females to mate with males is not a
consequence of the females' inability to elicit vigorous courtship. Copyright
1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
Association for the Study of Animal Behaviour.
PMID- 9642008
TI - Functional referents and acoustic similarity: field playback experiments with
rhesus monkeys.
AB - Rhesus monkeys, Macaca mulatta, on the island of Cayo Santiago, Puerto Rico
produce one or more of five acoustically distinctive calls when they find food.
Three of these calls ('warbles', 'harmonic arches' and 'chirps') are produced by
individuals finding high-quality, rare food items, whereas the other two calls
('coos' and 'grunts') are produced upon encountering lower-quality, common food
items, and in non-food contexts as well. To determine how rhesus classify such
acoustic variation, I conducted habituation experiments using a subset of the
five call types. I designed experiments to reveal whether classification is based
primarily on acoustic features or on the basis of a call's functional referent;
caller identity was held constant within sessions. Habituation to 'warbles'
transferred to 'harmonic arches', and vice versa. Thus, although these two calls
are acoustically distinctive, they appeared to be perceptually clustered into one
category based on referential similarities. In contrast, habituation to 'grunts'
was followed by dishabituation to 'warbles' or 'harmonic arches', and habituation
to 'warbles' or 'harmonic arches' was followed by dishabituation to 'grunts'.
Dishabituation could be due to acoustic or referential differences.
Significantly, the magnitude of the dishabituating response was asymmetric and
depended upon the call type used in the habituation series. Thus, when subjects
were habituated to 'grunts', they responded significantly more to tests of
'warbles' or 'harmonic arches' than when the sequence was reversed. These results
suggest that for rhesus monkey food-associated calls, referential differences
carry more weight during perceptual classification than do acoustical
differences. Copyright 1998 The Association for the Study of Animal Behaviour.
Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9642009
TI - Prey availability and selective foraging in shorebirds.
AB - Accurate measurements of prey availability are vital to our understanding of
foraging behaviour, particularly prey selectivity. In the present study,
observations of shorebirds foraging for fiddler crabs on intertidal mudflats
demonstrate that prey availability depends both on the temporal variation in crab
activity and on the crabs' responses to the presence of foraging shorebirds. Our
results suggest that measurements of prey availability that do not specifically
account for prey activity patterns and their responses to predators are
neccessarily inaccurate. Furthermore, our results also show that tests for
foraging selectivity are extremely sensitive to the way in which prey
availability is measured and can even indicate active prey selectivity when more
accurate measures of prey availability show predators to be non-selective.
Because inaccurate measures of food resources greatly reduce our ability to
detect food preferences, greater care must be taken to account for prey activity
patterns and their responses to predators in measurements of prey availability.
Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
The Association for the Study of Animal Behaviour.
PMID- 9642010
TI - Dominance between booby nestlings involves winner and loser effects.
AB - Two-chick broods of the blue-footed booby, Sula nebouxii, ordinarily exhibit
stable dominance-subordinance, with the senior (first-hatched) chick habitually
aggressive and the junior one habitually submissive (Nelson 1978, The Sulidae:
Gannets and Boobies. London: Oxford University Press). But are both the
subordinate and the dominant chick affected in their agonistic tendencies by
early social experience? To answer this, we permanently paired subordinate and
dominant chicks, 2-3 weeks old, with singletons (chicks lacking experience with a
nestmate) by cross-fostering. During the first 4 h after pairing, subordinate
chicks were seven times less aggressive than singletons and twice as likely to be
submissive; dominant chicks were six times as aggressive as singletons. Although
most subordinates consistently lost agonistic encounters during the first 10 days
after pairing, the proportion of dominants that won decreased progressively
until, by day 6, only about half of dominant chicks were winning. Early social
experience has a strong but reversable training effect on both subordinates and
dominants. Training as a subordinate showed more persistent effects than training
as a dominant, possibly in part because our testing situation perpetuated
subordinate training and counteracted dominant training. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9642011
TI - Moult speed predicts pairing success in male harlequin ducks.
AB - The bright plumage of male ducks in sexually dichromatic species is thought to
have evolved through intense sexual selection. This study examined the
relationship between the timing and speed of moult into this bright plumage and
subsequent mating success of male harlequin ducks, Histrionicus histrionicus.
Males that moulted relatively slowly had a lower chance of establishing a pair
bond than others. The timing of moult was unrelated to whether a male obtained a
mate. Moult speed and timing were not correlated within individual males, but
were significantly repeatable in individual males over 2 years. Moult speed
probably reflects the condition of males, whereas timing of moult is more likely
to be related to the distance to an individual's breeding area, which determines
the timing of arrival to the moulting grounds. In waterfowl species that have
been studied, males usually form dominance hierarchies before pairing and females
tend to choose dominant males. We suggest that male harlequin ducks that moult
slowly are poor-quality individuals, which are relegated to subordinate status
and are unlikely to attract a mate the following autumn. Copyright 1998 The
Association for the Study of Animal Behaviour. Copyright 1998 The Association for
the Study of Animal Behaviour.
PMID- 9642012
TI - Estimating ancestral states of a communicative display: a comparative study of
Cyclura rock iguanas.
AB - In this study we describe the signature headbob displays of seven of the eight
extant species of Cyclura iguanas using data collected from the field and from
captive animals. We used phylogenetic comparative methods to estimate the
ancestral states of several measures of the headbob displays, including number of
headbobs and the duration of headbobs and inter-bob pauses. Divergence in the
headbob display among species has been substantial, with some major changes
occurring within only a few (about six) generations. Otherwise, results are
consistent with those obtained previously for other lizards which suggest that
there is an evolutionary limit on the total duration of headbob displays.
Differences in the results obtained using different phylogenetic methods suggest
that although estimates of ancestral states are reasonably robust to violations
of evolutionary assumptions, we cannot determine the standard errors of those
ancestral phenotypes accurately without more detailed information about the types
of forces (e.g. selection, drift) underlying evolutionary change in these traits.
In particular, within-species variation had a substantial impact on the standard
errors of estimated ancestral states, and should be included in such estimations
whenever possible. Finally, our results emphasize the importance of conserving
behavioural as well as genetic diversity in trying to preserve endangered species
for possible reintroduction into the wild. Copyright 1998 The Association for the
Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
Behaviour.
PMID- 9642013
TI - The influence of tail autotomy on agonistic behaviour in a territorial
salamander.
AB - Assessment of potentially asymmetrical characters (such as fighting ability and
resident advantage) is often important in determining the outcome of agonistic
interactions. Loss of body parts, a predator defence mechanism used by many
animals, may lead to a reduction in fighting ability and may be easily assessed
by competitors. We investigated the influence of tail loss on the expression of
agonistic behaviour in the territorial red-backed salamander, Plethodon cinereus.
Residents and intruders were matched for body size, and pairs were tested in all
combinations of tailed or tailless residents with tailed or tailless intruders.
Neither residents nor intruders altered their behaviour based on their own tail
condition, but they did alter their behaviour based on the tail condition of
their opponents. Intruders showed more aggression or less submission towards
tailless residents than towards tailed residents. When contests were between
residents and intruders of the same tail condition (both tailed or tailless),
intruders were more aggressive towards residents when both were tailless than
when both were tailed, indicating that tail loss does not directly hamper
aggressive displays. In contests where the asymmetry between residents and
intruders was small (based on tail condition and residency status), intruders
showed more aggression and less submission than in contests where the asymmetry
was large. Residents did not differ in their behaviour for most comparisons.
Thus, for intruders, the tail condition of residents is an important determinant
of agonistic behaviour displayed in territorial contests. For residents, factors
other than tail condition (such as resource value) may be more likely to
influence their behaviour. Copyright 1998 The Association for the Study of Animal
Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9642014
TI - Greater spear-nosed bats discriminate group mates by vocalizations.
AB - Individuals often benefit from identifying their prospective social partners.
Some species that live in stable social groups discriminate between their group
mates and others, basing this distinction on calls that differ among individuals.
Vocalizations that differ between social groups are much less common, and few
studies have demonstrated that animals use group-distinctive calls to identify
group mates. Female greater spear-nosed bats, Phyllostomus hastatus, live in
stable groups of unrelated bats and give audible frequency, broadband calls
termed screech calls when departing from the roost and at foraging sites.
Previous field observations suggested that bats give screech calls to coordinate
movements among group members. Prior acoustic analyses of 12 acoustic variables
found group differences but not individual differences. Here, we use the same
acoustic variables to compare calls from three cave colonies, and find that calls
differ between caves. We also report results from field and laboratory playback
experiments designed to test whether bats use acoustic differences to
discriminate calls from different colonies, groups or individuals. Results from
field playbacks indicate that response depends on the cave of origin, indicating
that bats can discriminate among calls from different caves. This discrimination
ability may be based, in part, on whether calls are familiar or unfamiliar to the
listening bats. Laboratory playbacks demonstrate that bats discriminate calls
given by their group mates from calls given by other bats from the same cave
irrespective of familiarity. However, these experiments provide no evidence that
bats discriminate among individuals. Previous field work indicates that females
that forage with social group mates may benefit from shared information about
food or mutual defence of feeding sites. Indicating group membership is
essential, since these benefits appear to be restricted to group mates. Copyright
1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
Association for the Study of Animal Behaviour.
PMID- 9642017
TI - Contents of Volume 55
AB - No Abstract Copyright 1998 The Association for the Study of Animal Behaviour.
PMID- 9642018
TI - Semantic factors in verb retrieval: an effect of complexity.
AB - Aphasic patients often have more difficulty retrieving verbs than nouns. We
present data from eight aphasics demonstrating that they have a selective
impairment for verb retrieval. We then explore the role of semantic complexity
(i.e., the number of semantic features) in verb retrieval using a delayed
repetition/story completion task. The results indicate that six of the patients
are better at retrieving semantically complex verbs (e.g., run) than semantically
simpler verbs (e.g., go). The results have implications for accounts of the
noun/verb dissociation in aphasia, as well as for theories of verb
representation.
PMID- 9642019
TI - Cognitive mechanisms for processing nonwords: evidence from Alzheimer's disease.
AB - Repetition and reading of various types of pronounceable nonwords (pseudowords)
was examined in patients with probable Alzheimer's disease (AD) and healthy
elderly controls. Overall accuracy of performance was lower in AD patients
compared to controls, but the two groups showed qualitatively similar response
patterns when reading different kinds of pseudowords aloud and when repeating
pseudowords composed of familiar phonological forms, analogous to those in real
English words. AD patients diverged in performance from controls, however, when
repeating pseudowords composed of phonologically unusual forms. These results
support two conclusions: (1) Aspects of phonological processing may become
disrupted in AD patients in association with increasing dementia severity, while
orthographic processing remains comparatively less impaired. (2) The results are
consistent with the view that the processing of pseudowords is achieved through
the same system as real words, and further show that the influence of prior
language experience on the processing of novel linguistic forms occurs primarily
at the level of phonological, rather than orthographic processing.
PMID- 9642020
TI - Selective kana jargonagraphia following right hemispheric infarction.
AB - A strongly right-handed Japanese man showed an unusual writing disorder
associated with Broca-type aphasia after suffering a right hemispheric
infarction. Writing with his right hand produced a fluent output in contrast to
his nonfluent speech. The patient's agraphia disproportionately affected the
writing of kana (Japanese syllabograms), leaving relatively intact the writing of
kanji (Japanese ideograms). His kana agraphia, consisting of substitutions,
intrusions, transpositions, and deletions, became apparent as the number of
syllables in target words increased. Quantitative analysis of the substitutions
in terms of their phonological similarity to the target revealed that most of the
substitutions were phonologically dissimilar. Those errors were distributed
almost identically for familiar and novel words. Moreover, the errors were
observed asymmetrically across the target: more errors occurred near the end than
at the beginning of a word. The kana agraphia in association with fluent writing
output resulted in kana jargonagraphia. These observations suggest that our
patient's selective kana jargonagraphia is best explained by selective damage to
the hypothesized kana graphemic buffer and by disinhibition of the motor engrams
of writing behavior, both of which resulted from right hemispheric damage.
PMID- 9642021
TI - The contribution of attentional mechanisms to an irregularity effect at the
graphemic buffer level.
AB - This study analyzes acquired dysgraphia observed in a French-speaking woman. The
results point to an impairment of the graphemic buffer, i.e., the processing
stage where abstract orthographic representations are temporarily stored while
planning the written production. However, the spelling errors were more frequent
in the irregular than in the regular words. A qualitative analysis of the errors
in the irregular misspelled words showed that, in general, these were not
"regularization" errors, but rather the same characteristics as the
phonologically implausible errors found in the regular words, such as letters
substitutions, deletions, additions, and transpositions. Furthermore, in a list
of regular and irregular words of same length and graphemic structure, the errors
not only tended to concentrate on the irregularity itself but also tended to be
more frequent elsewhere in the irregular words compared to the regular words.
These finding are discussed in terms of a post-lexical sensitivity to irregular
spelling. It is also shown that when focusing attention on the irregularity
becomes necessary, this can cause a detriment to the surrounding graphemic
constituents. Interaction between attentional resources and processing of
orthographic representations at the graphemic buffer level is considered.
PMID- 9642022
TI - Why does monitoring fail in jargon aphasia? comprehension, judgment, and therapy
evidence.
AB - Many people with jargon aphasia seem unaware of their speech disorder. The first
section of this paper reports data from four subjects which indicate that self
monitoring can fail even when subjects' input skills are apparently adequate to
detect their errors. Explanations for this dissociation have attributed
monitoring failure to a deficit in auditory feedback, or to a resource limitation
which prevents concurrent speaking and monitoring. Section 2 reports a series of
naming and judging experiments with one of the subjects which rule out these
explanations. These show that the subject can detect his neologisms when he is
repeating, but not when he is naming. These results suggest that his monitoring
difficulties arise when he is accessing phonology from semantics. Section 3
presents a study which supports this inference, since it shows that semantically
focused intervention yields improvements in self-monitoring. It is concluded (1)
that monitoring failure can arise from deficits within the production process
which preclude comparison of actual with intended output, and (2) that this
deficit is best explained within a connectionist model in which monitoring is
performed by feedback mechanisms in the word production process.
PMID- 9642023
TI - Cerebral networks and functional brain asymmetry: evidence from regional
metabolic changes during word repetition.
AB - Word repetition causes a significant bilateral metabolic increase in both
superior temporal cortices. Frontal speech areas are less activated despite their
presumable speech competence. We investigated in this study the relationship
between frontal and temporal cortical areas during word repetition. We measured
regional cerebral metabolic rates of glucose (CMRGI) in 15 normal subjects with
positron emission tomography (PET) at rest and during word repetition.
Significant correlations connected frontal and temporal areas of both
hemispheres, notwithstanding their different levels of mean metabolic activation.
The left planum temporale was a hub of significant interregional correlations, in
contrast to its contralateral mate. This study indicates that an asymmetric
network of significant connections orchestrates the speech-relevant cortical
areas according to the actual needs of speech processing.
PMID- 9642024
TI - Visual half-field Stroop effects with spatial separation of words and color
targets.
AB - Past inconsistencies in the occurrence of differential visual half-field Stroop
effects were addressed in two experiments using a visual half-field presentation
technique incorporating brief displays (100 ms) and a fixation task designed to
ensure proper eye fixation at display onset. Experiment 1 used displays in which
distractor words and color targets were presented in contralateral visual fields.
Experiment 2 compared contralateral with ipsilateral displays where words and
color targets appeared one above the other in the same visual field. Stroop
effects were larger whenever a word occupied the right as opposed to the left
visual field, regardless of whether the color target was left or right. Results
are consistent with the idea that words are processed more efficiently or
automatically in right visual field/left hemisphere presentations.
PMID- 9642025
TI - Intact higher-level constraints on the pronunciation of new written words by
nonfluent dysphasics.
AB - Nonfluent, Broca-type dysphasics are characterized by impaired syntactic
processing. However, grammaticality judgements and certain on-line tasks have
shown some preservation of this processing in such subjects. We report an
experiment with nonfluent dysphasics in which they read aloud th-initial nonwords
(e.g., thuz) in sentential contexts that predicted a function word or a content
word. This paradigm was first used by Campbell and Besner (1981) to demonstrate
syntactic effects on pronunciation: normal subjects pronounce word-initial th- as
voiced in function word contexts and unvoiced in content word contexts,
reflecting a regularity in the English lexicon. Poorer performance by the
dysphasic subjects on this task is the default prediction of most "syntactic"
accounts of agrammatism, including an account based on the impairment of
functional projections, which we discuss. We replicate Campbell and Besner's
effect in our normal control group and in the dysphasic group, with no
significant difference between the two groups. We conclude that syntactic
influences on pronunciation may be unimpaired in nonfluent dysphasia, and that
the task used resembles the class of online tasks, in its capacity to elicit
unimpaired processing. We argue that this result is compatible with the account
of agrammatism discussed if the latter is grounded in a distributed, constraint
based processing device allowing graceful degradation of functioning.
PMID- 9642027
TI - The 'drug value' in the European pharmaceutical system.
AB - European regulatory authorities (EMEA, European Commission) and/or national
pharmacological and medical decision-makers can utilise the drug value to help
themselves to decide which drugs to define as really innovative instead of new,
which regulations to implement, which drugs to include on formularies, or which
restrictions to enforce. As economic research becomes widely accepted for
pharmaceutical evaluation, it needs to utilise prospective rather than
retrospective study design. Analyses conducted at the time of therapy have better
access to patients and can obtain both more accurate information on consumption
of resources and the impact of pharmacotherapy on non-monetary quality of life
for patients, survival, comparative clinical effectiveness and economic outcomes
within social health service or in wider economy.
PMID- 9642028
TI - Evidence-based medicine criteria applied to hypolipidemic and antihypertensive
drug trials: is drug efficacy always the same?
PMID- 9642029
TI - Captopril in the management of patients after acute myocardial infarctions. A
cost effectiveness analysis in Italy.
AB - The prevalence of acute myocardial infarction (AMI) is found in approximately
500,000 individuals in Italy. The annual incidence can be crudely estimated to be
100,000 events. This represents a major health care problem and generates
questions about the rational allocation of public resources devoted to health
care, specially since Italy has a National Health Service. We focused on the
economics of adding captopril administration to standard care in Italy in AMI
patients matching the entry criteria of the SAVE study. The cost effectiveness
ratio(s) was explored under different assumptions on the effectiveness and on the
cost of the intervention. In our base case, administering captopril has an
incremental Cost Effectiveness Ratio of 14.708 million lira (1 US $ = 1529 lira
in December 1996) per life year saved (LYS) (maximum range 7.171-21.003). This
means that a net investment to the NHS of approximately 12 billion lira over 4
years to treat 10,000 patients matching the entry criteria of the SAVE trial will
prevent 410 cardiovascular deaths (i.e. 33.229 million lira per cardiovascular
death prevented) and save approximately 928 (discounted) to 1027 (not discounted)
LYS over the same time period. Results are sensitive to the cost of captopril and
of revascularisation procedures.
PMID- 9642030
TI - Antiallergic/antiasthmatic activity of oligopeptide related to IgE.
AB - In spite of continuous research in the field of bronchial asthma, still no
satisfactory drug is available. Recently a new class of oligopeptide exhibited
antiallergic activity by inhibiting the synthesis of IgE antibody. The analogue
of ADSDGK (94-335) has shown antiallergic activity in experimental models. The 94
335 inhibited the passive cutaneous anaphylaxis (PCA) reactions in rats in a dose
dependent manner (0.5-10 mg kg-1 p.o.) by 47-90%. There was a 70-87% protection
of mast cell degranulation induced by compound 48/80 with peptide 94-335 at 0.5
1.5 mg kg-1 p.o. in rats. This peptide also inhibited antigen- induced
contraction in sensitised guinea pig ileum. There was 18 and 72% protection to
bronchoconstriction induced by histamine and egg albumin, respectively, in an
aerosol test in guinea pigs. These effects of compound 94-335 were comparable
with that of the clinically-used antiallergic drug disodium cromoglycate (DSCG).
The results suggest that peptide 94-335 possesses potent antiallergic activity.
PMID- 9642031
TI - The localisations in liposomal membranes of the tetrahydrofuran ring moieties of
the annonaceous acetogenins, annonacin and sylvaticin, as determined by 1H NMR
spectroscopy.
AB - The positions of the tetrahydrofuran (THF) ring moieties of annonacin (a mono-THF
ring Annonaceous acetogenin) and sylvaticin (a non-adjacent bis-THF ring
Annonaceous acetogenin) within liposomal membranes made of
dimyristoylphosphatidylcholine (DMPC) were determined by proton (1H) nuclear
magnetic resonance (NMR) spectroscopy. Based on 1H intermolecular nuclear
Overhauser effects (NOEs), the THF rings of both acetogenins studied reside near
the polar interfacial head group region of the DMPC. Recently, we have reported
that the THF rings of a series of asimicin type of Annonaceous acetogenins (with
adjacent bis-THF rings) also reside near the interfacial head group of DMPC. We
can now conclude that the Annonaceous acetogenins, containing either mono-,
adjacent bis-, or non-adjacent bis-THF ring moieties, have their THF ring
moieties at the interfacial region of membranes, i.e., the THF ring moiety seems
to serve a role as an anchor in the lipid membranes. This may be related to the
uniquely potent bioactivities that Annonaceous acetogenins exhibit at their
enzyme-inhibitory sites within mitochondrial and plasma membranes.
PMID- 9642032
TI - Evidence for the stabilisation of the high-affinity state of beta-adrenoceptors
by an endogenous factor in rat brain.
AB - Inhibition of binding of the labelled antagonist (-)[3H]CGP 12177 by the full
agonist (-)isoproterenol results in shallow competition curves, characteristic of
the presence of both high- and low-affinity states of beta-adrenoceptors
(betaAR). When in excess, the GTP analog 5'-guanylylimidodiphosphate (GppNHp) is
expected to convert all receptors in the high-affinity state to the low-affinity
state. However, in the rat cortex and cerebellum synaptosomes, a proportion of
the betaAR in the high-affinity state was GppNHp-insensitive. This apparent
GppNHp-insensitivity decreased with decreasing temperature of incubation.
Moreover, it was totally abolished by the gentle treatment of membranes with 3
[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). We propose that
a protein factor interacts with the betaAR/Gs protein complex and that it induces
the GppNHp-insensitivity. This factor would be released by CHAPS in a functional
form because it may regenerate the GppNHp-insensitivity after concentration and
reconstitution with CHAPS-treated membranes. It is likely that the factor acts as
a stabiliser of betaAR in the high-affinity state.
PMID- 9642033
TI - Effect of non-steroidal anti-inflammatory drugs on the anticonvulsive activity of
valproate and diphenylhydantoin against maximal electroshock-induced seizures in
mice.
AB - Prostaglandins and their inhibitors may affect convulsive phenomena. Thus, the
aim of this study was to examine possible interactions between non-steroidal anti
inflammatory drugs and two conventional antiepileptic drugs in terms of their
anticonvulsive activity and side-effects. Also, the plasma levels of
antiepileptics were measured in order to delineate possible pharmacokinetic
interactions. The following non-steroidal anti-inflammatory drugs (NSAIDs) were
studied: acetylsalicylic acid, ibuprofen, indomethacin, metamizole, paracetamol
and piroxicam. None of these drugs affected the threshold for electroconvulsions.
However, all NSAIDs studied enhanced the protective activity of valproate
magnesium against maximal electroshock-induced seizures. Only ibuprofen and
piroxicam enhanced the anticonvulsive activity of diphenylhydantoin. Ibuprofen
decreased the ED50 value of valproate (for the induction of motor impairment) in
the rotorod test, whilst piroxicam reduced the ED50 value of valproate in rotorod
and chimney tests. Diphenylhydantoin combined with either ibuprofen or piroxicam
did not cause any motor impairment in these tests. The total plasma level of
valproate and free plasma level of diphenylhydantoin remained unchanged in the
presence of all studied NSAIDs. These data demonstrate that NSAIDs could enhance
the protective activity of antiepileptics. However, in case of valproate it may
be associated with the severe side effects.
PMID- 9642034
TI - Differences in the effects of vasopressin and oxytocin on feline gastric corpus
motility: selective action of vasopressin on longitudinal muscle.
AB - The effect of vasopressin and oxytocin on the contractile activity of
preparations isolated from the feline gastric corpus wall was investigated.
Vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M), but not oxytocin, evoked concentration
dependent tonic contractions only of longitudinal muscle strips. At the same
time, vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M) potentiated the magnitude of
amplitudes, but not the frequency, of spontaneous contractions. Both the
vasopressin V1 receptor antagonist d(CH2)5-(Me)2-Tyr-AVP and the predominantly
vasopressin V2 receptor antagonist d(CH2)5, D-Ile2, Ile4-AVP, the non-selective
muscarinic receptor antagonist, atropine, the predominantly selective muscarinic
M1 receptor antagonist, pirenzepine, the predominantly selective muscarinic M2
antagonist, methoctramine, the predominantly selective muscarinic M3 receptor
antagonist, para-fluoro-hexahydro-siladifenidol, and the calcium channel blocker,
nifedipine, but not the ganglion blocking agent, mecamylamine, depressed or
blocked the tonic contractions induced by vasopressin. Among the antagonists,
only atropine and nifedipine inhibited the spontaneous contractions. On the other
hand, the anticholinesterase, physostigmine, potentiated both the vasopressin
induced tonic and spontaneous contractions. With regard to the receptors, the
vasopressin-induced tonic contractions are mediated at least in part through
vasopressin V1 and V2 receptors, non-selective muscarinic and selective
muscarinic M1, M2 and M3 receptors. The increase in amplitudes of spontaneous
contractions is mediated only via-nonselective muscarinic receptors. Vasopressin
receptors appear to be located mostly pre-synaptically, although the direct
effect of vasopressin on post-synaptic receptors cannot be excluded. The pA2
values suggests rather V1a than V1b vasopressin receptor subtype involvement in
tonic contractions vasopressin had produced. The tonic as well as spontaneous
contractions are calcium-dependent. In addition, these results point to the
existence of non-selective muscarinic receptors, which participate in the
regulation of both tonic and spontaneous contractions, while muscarinic M1, M2
and M3 receptors subserve only the tonic contractions.
PMID- 9642035
TI - Response to isoproterenol of rabbit detrusor strips following exposure to NSAIDs.
AB - To ascertain whether NSAIDs affect the physiological mechanisms involved in
bladder detrusor muscle motility we investigated the influence of indomethacin,
ibuprofen and acetyl salicylic acid on the beta-adrenergic-evoked response in
isolated male-rabbit detrusor strips. Incubation with indomethacin for 60 min
significantly reduced the tissue response to isoproterenol (up to 10.8+/-4.9%),
entirely abolished spontaneous contractions and caused a fall in basal tone.
Ibuprofen significantly inhibited the tissue response to isoproterenol (up to
25.5+/-5.8%), abolished spontaneous contractions and caused a fall in basal tone.
After the spasmogen KCl had been added to restore basal tone, the highest
indomethacin and ibuprofen concentrations still significantly inhibited the
isoproterenol-evoked response, indomethacin being the most active compound.
Acetyl salicylic acid, at the doses used, neither inhibited spontaneous
contractions nor changed basal tone whereas it significantly inhibited tissue
response to isoproterenol (up to 69. 6+/-4.6%). Our findings in rabbit detrusor
strips show that NSAIDs affect the beta-adrenergic-evoked response. They probably
do so mainly through mechanisms other then inhibition of prostaglandin
production.
PMID- 9642036
TI - Changes in the nitric oxide system of rat myometrium during midgestation and
delivery at term.
AB - The aims of this study were to investigate whether a nitric oxide (NO) system is
present in the pregnant rat myometrium and whether it differentially inhibits
myometrial contractility during midgestation and delivery at term. Myometrial
strips were obtained from eight rats at midgestation (day 16) and eight rats
during delivery at term, and mounted in an organ bath for assessment of isometric
tension. There were scarce spontaneous contractions with gradually increased
amplitude that ceased after short periods at midgestation, whereas the frequency
of spontaneous contractions increased and were regular, and the amplitude of
contractions became stable and long lasting during delivery. Spontaneous and
carbachol- induced contractions were decreased by L-arginine and increased by NG
nitro-L-arginine methyl ester (L-NAME) at midgestation and delivery, but much
higher concentrations of L-arginine and L-NAME were required to obtain this
effect at delivery. These results show: (1) that there is basal and carbachol
stimulated production of NO in pregnant rat myometrium; (2) that the L-arginine
NO system inhibits myometrial contractility; (3) that the effect of the L
arginine-NO system is elevated at midgestation and decreased during delivery; and
(4) that the L-arginine-NO system may contribute to uterine quiescence during
gestation and the initiation of labour at term.
PMID- 9642037
TI - The site of action of furosemide.
AB - To establish whether furosemide (F) acts on the proximal tubule beside the thick
ascending limb of Henle's loop, we reviewed the data from 55 rats studied before
and during the i.v. infusion of 10 mg kg-1 of furosemide. These animals were the
object of previously published studies. SNGFR was 42.6+/-1.1 nl min-1 during
baseline conditions (B), 42.7 nl min-1 during F (P>0.9). In 151 paired last
proximal tubular samples, percentage reabsorption was 71.72 before and 71.72%
after F (P=1.0). In 64 paired early distal tubular samples, percent reabsorption
fell from 86% in B to 78% during F (P<0.0001). During F, the urine flow rate
expressed as a percentage of GFR (24+/-2%) was significantly correlated (R=0.52,
P<0.0001) with the percent delivery of filtrate out of the proximal tubule (26+/
3%). These data demonstrate that, even at this very high dosage, F does not act
on the proximal tubule. It inhibits transport on the ascending limb of Henle's
loop. By allowing the delivery of isotonic tubular fluid to the distal tubule, it
causes a fall in volume absorption along the early distal convolution in
proportion to its baseline water permeability. It increases urine flow by
abolishing the interstitial hypertonicity and, consequently, the osmotically
driven solvent flow across the distal epithelium and collecting ducts. Therefore
the urine flow rate during F closely approximates volume delivery out of the
proximal tubule.
PMID- 9642038
TI - Pattern of antimicrobial drug prescribing and prescriptive behaviour for acute
otitis media among physicians in Sicily.
AB - Acute otitis media (AOM) is one of the most common diseases of childhood, but it
is less common in adults. Usually, in clinical practice therapy cannot wait until
the laboratory report and the choice of an antibiotic prescription is initiated
on an empirical basis. Moreover, several studies have shown great variability in
antibiotic prescription for AOM. The study was carried out in order to describe
the antibiotic prescribing pattern and the prescriptive behaviour among Sicilian
general practitioners (GPs) in choosing an empirical antibiotic regimen for
treatment of AOM. Each GP completed a questionnaire for each therapeutic
intervention which ended with an antibiotic prescription. Diagnoses and drugs
were classified according to the International Classification of Diseases (ICD
10) and to the Anatomical Therapeutic Chemical (ATC) classification system,
respectively. Antibiotics, issued for AOM, accounted for 11.1% of total
antimicrobial therapy in paediatrics and 3.4% in adults. The commonest
therapeutic groups were: cephalosporins (44.1%), macrolides (26.1%), extended
spectrum penicillins (16.1%), combination of penicillins and beta-lactamase
inhibitors (11.4%). The route of administration appeared to be influenced by age
of the patients, by a subjective clinical assessment of disease severity and by
the presence of concurrent diseases. The diagnostic criteria and the marked
variation in antibiotic prescribing pattern for AOM among Sicilian GPs reflects a
lack of knowledge of any local or national guidelines.
PMID- 9642039
TI - Announcements
AB - Copyright 1998 The Italian Pharmacological Society .
PMID- 9642040
TI - Identification of a phosphodiesterase I/nucleotide pyrophosphatase-related gene
mRNA in rat vascular smooth muscle cells by the differential display approach.
AB - Vascular smooth muscle cell hypertrophy and proliferation may participate in the
pathophysiology of cardiovascular disease. The analysis of changes in gene
expression in vascular smooth muscle cells is crucial to the understanding of the
molecular biology of cardiovascular disease. An effective method for analysis of
gene expression is the differential display approach. Applying the differential
display approach, we identified a gp130RB13-6-related gene in vascular smooth
muscle cells following stimulation with platelet-derived growth factor-BB and
angiotensin II. It is well known that gp130RB13-6 is a
phosphodiesterase/nucleotide pyrophosphatase. Northern blotting and reverse
transcriptase-polymerase chain reaction analysis revealed a dramatic down
regulation of the gp130RB13-6-related mRNA after six hours of stimulation of the
cells with both agonists. Recently, gp130RB13-6 was identified as a rat neural
differentiation and tumor cell surface plasma membrane glycoprotein. These
findings demonstrate that the expression of gp130RB13-6 mRNA in vascular smooth
muscle cells is remarkably regulated by growth factors and therefore may play an
important role in the regulation of vascular smooth muscle cell growth.
PMID- 9642041
TI - RNA polymerase mutants that destabilize RNA polymerase-promoter complexes alter
NTP-sensing by rrn P1 promoters.
AB - Mutations in Escherichia coli rpoB or rpoC, selected for the ability to confer
prototrophy on relA spoT strains, were found to affect transcription from rrn P1
promoters. Two mutant strains (beta RH454 and beta' delta 215-220) reduced
transcription of rrn P1 core promoter-lacZ fusions but not of control promoter
lacZ fusions. Purified mutant RNAPs formed complexes with rrn P1 promoters that
were much less stable than those formed by wild-type RNAP and required high
concentrations of the initiating NTP for efficient rrn P1 transcription. The
instability of the rrn P1 core promoter complexes with the mutant RNAPs and their
altered regulatory properties support a recently proposed model for the control
of rRNA transcription by changing concentrations of the initiating NTPs. We
further suggest that destabilization of promoter complexes by the mutant RNAPs
mimics effects of ppGpp, decreasing or increasing transcription depending on the
kinetic properties of the specific promoter.
PMID- 9642042
TI - Structure and NTPase activity of the RNA-translocating protein (P4) of
bacteriophage phi 6.
AB - The RNA polymerase complex of bacteriophage phi 6 comprises four proteins, P1,
P2, P4 and P7, and forms the core of the virion. Protein P4 is a non-specific
NTPase that provides the energy required for RNA translocation (packaging).
Characterization of purified recombinant P4 shows that the protein assembles into
stable hexamers in the presence of ADP and divalent cations. Image averaging of
electron micrographs reveals this hexamer as a slightly skewed ring with outer
and inner diameters of 12 and 2 nm, respectively. NTPase activity of P4 is
associated only with the hexameric form. Ca2+ and Zn2+ and non-specific single
stranded RNA stimulate the NTPase activity, while Mg2+ acts as a non-competitive
inhibitor, presumably via a separate Mg2+ binding site. Binding affinities of
different nucleotide mono-, di- and triphosphates and non-hydrolyzable analogs
indicate that the beta-phosphate moiety is required for substrate binding. A
slight preference for binding of purine nucleotides is also observed. Analysis of
P4 by CD and Raman spectroscopy indicates an alpha/beta subunit fold that is
altered only slightly by hexamer assembly. Raman markers of P4 secondary and
tertiary structures are also largely invariant to nucleotide exchange and
hydrolysis, suggesting that the mechanisms of RNA translocation involves movement
of subunits relative to one another rather than large scale changes in the
alpha/beta subunit fold. The stoichiometry of P4 in the mature phi 6 virion is
estimated as 120 copies. Because the recombinant P4 hexamers exhibit hydrodynamic
and enzymatic properties that are identical to those of P4 oligomers released
from native phi 6, we propose that P4 occurs as hexamers in the native viral core
particle.
PMID- 9642043
TI - A toggle duplex in hepatitis delta virus self-cleaving RNA that stabilizes an
inactive and a salt-dependent pro-active ribozyme conformation.
AB - The antigenomic RNA of hepatitis delta virus (HDV) can form a short duplex, P2a,
in which a four-nucleotide sequence within the self-cleaving domain pairs with a
sequence just outside the previously defined 3'-boundary of the ribozyme. Both
sequences that would participate in forming P2a were previously determined to be
non-essential for self-cleavage activity. Ribozymes able to form P2a were less
active than those lacking the 3' P2a sequence when preincubated under the
standard low-Na+ conditions. Chemical probing of the RNA correlated base-pairing
in P2a with this inhibition. Furthermore, mutagenesis and 3' truncation
experiments mapped the inhibitory sequence to P2a. However, raising the NaCl
concentration in the preincubation prior to adding Mg2+ reversed the inhibitory
effect. Moreover, with NaCl preincubation, the P2a-containing ribozyme was more
active than an otherwise identical ribozyme lacking the 3' P2a sequence. Non
denaturing gels provided evidence for alternative conformations of the P2a
containing precursor with only the faster-migrating species correlating with the
active form. A difference in the temperature-dependence for the rate of cleavage
of the P2a-containing ribozyme with and without NaCl, together with a difference
in the melting behavior of the RNA in NaCl with and without P2a, suggested that
P2a favors the native structure in NaCl. Many derivatives of the HDV ribozymes
form inactive conformers; however, this study reveals details of a specific
structure that stabilizes both inactive and active conformations of the HDV
ribozyme.
PMID- 9642044
TI - Fanconi anemia C gene product plays a role in the fidelity of blunt DNA end
joining.
AB - Mutations in genes controlling the correct functioning of the replicative, repair
and recombination machineries may lead to genomic instability. A high level of
spontaneous chromosomal aberrations amplified by treatment with DNA cross-linking
agents is the hallmark of Fanconi anemia (FA), an inherited chromosomal
instability syndrome associated with cancer proneness. Two of the eight FA genes
have been cloned (FAA and FAC), but their function has not yet been defined. The
lack of homology with known genes suggests the involvement of FA genes in a novel
pathway specific to vertebrates. Using a DNA end-joining assay in cultured cells,
we studied the processing of both blunt and cohesive-ended double strand breaks
(DSB) in normal and FA cells. The results show that: (i) the overall ligation
efficiency is normal in FA lymphoblasts; (ii) in FA-C, error-free processing of
blunt-ended DSB is markedly decreased, resulting in a higher deletion frequency
and larger deletion size; (iii) the fidelity of processing of blunt-DSB is
completely restored in FACC cells (complemented with wild-type FAC gene) and the
deletion size shifted to values similar to that observed in normal cells; (iv)
the fidelity of cohesive end-joining is not affected in FA cells; (v) activities
and/or expression of known factors involved in DSB processing, such as the
components of the DNA-PK complex and XRCC4, are normal in FA cells. Our results
provide strong evidence that the lack of a functional FAC gene results in loss of
fidelity of end-joining, which likely accounts for the FA-C phenotype of
chromosome instability. We conclude that FAC, and perhaps all FA gene products,
are likely to play a role in the fidelity of end-joining of specific DSB.
PMID- 9642045
TI - Orientation changes of fluorescent probes at five sites on the myosin regulatory
light chain during contraction of single skeletal muscle fibres.
AB - Changes in the orientation of the myosin regulatory light chain (RLC) in single
muscle fibres were measured using polarised fluorescence from
acetamidotetramethylrhodamine (ATR). Mutants of chicken skeletal RLC containing
single cysteine residues at positions 2, 73, 94, 126 and 155 were labelled with
either the 5 or 6-isomer of iodo-ATR, giving ten different probes. The labelled
RLCs were exchanged into demembranated fibres from rabbit psoas muscle without
significant effect on active force generation. Fluorescence polarisation
measurements showed that nine out of the ten probe dipoles were more
perpendicular to the fibre axis in the absence of ATP (in rigor) than in either
relaxation or active contraction. The orientational distribution of the RLC
region of the myosin head in active contraction is closer to the relaxed than to
the rigor orientation, and is not equivalent to a linear combination of the
relaxed and rigor orientations. Rapid length steps were applied to the fibres to
synchronise the motions of myosin heads attached to actin. In active contraction
the fluorescence polarisation changed both during the step, indicating elastic
distortion of the RLC region of the myosin head, and during the subsequent rapid
force recovery that is thought to signal the working stroke. The peak change in
fluorescence polarisation produced by an active release of 5 nm per half
sarcomere indicates an axial tilt of less than 5 degrees for all ten probes, if
all the myosin heads in the fibre respond to the length step. This tilting was
towards the rigor orientation for all ten probes, and could be explained by 14%
of the heads moving to the rigor orientation. An active stretch tilted the heads
away from the rigor conformation by a similar extent.
PMID- 9642046
TI - Correlation of the expansion segments in mammalian rRNA with the fine structure
of the 80 S ribosome; a cryoelectron microscopic reconstruction of the rabbit
reticulocyte ribosome at 21 A resolution.
AB - Samples of 80 S ribosomes from rabbit reticulocytes were subjected to electron
cryomicroscopy combined with angular reconstitution. A three-dimensional
reconstruction at 21 A resolution was obtained, which was compared with the
corresponding (previously published) reconstruction of Escherichia coli 70 S
ribosomes carrying tRNAs at the A and P sites. In the region of the intersubunit
cavity, the principal features observed in the 70 S ribosome (such as the L1
protuberance, the central protuberance and A site finger in the large subunit)
could all be clearly identified in the 80 S particle. On the other hand,
significant additional features were observed in the 80 S ribosomes on the
solvent sides and lower regions of both subunits. In the case of the small (40 S)
subunit, the most prominent additions are two extensions at the base of the
particle. By comparing the secondary structure of the rabbit 18 S rRNA with our
model for the three-dimensional arrangement of E. coli 16 S rRNA, these two
extensions could be correlated with the rabbit expansion segments (each totalling
ca 170 bases) in the regions of helix 21, and of helices 8, 9 and 44,
respectively. A similar comparison of the secondary structures of mammalian 28 S
rRNA and E. coli 23 S rRNA, combined with preliminary modelling studies on the 23
S rRNA within the 50 S subunit, enabled the additional features in the 60 S
subunit to be sub-divided into five groups. The first (corresponding to a total
of ca 335 extra bases in helices 45, 98 and 101) is located on the solvent side
of the 60 S subunit, close to the L7/L12 area. The second (820 bases in helices
25 and 38) is centrally placed on the solvent side of the subunit, whereas the
third group (totaling 225 bases in helices 18/19, 27/29, 52 and 54) lies towards
the L1 side of the subunit. The fourth feature (80 bases in helices 78 and 79)
lies within or close to the L1 protuberance itself, and the fifth (560 bases in
helix 63) is located underneath the L1 protuberance on the interface side of the
60 S subunit.
PMID- 9642047
TI - Analysis of striated fiber formation by recombinant SF-assemblin in vitro.
AB - The basal bodies of green flagellates are often connected to striated microtubule
associated fibers (SMAFs), which are highly ordered bundles of 2 nm filaments. SF
assemblin (33 kDa) is the principal structural subunit of the SMAFs and consists
of a non-helical head domain of approximately 32 residues and an alpha-helical
rod domain that shows a pronounced coiled-coil forming ability. To investigate
the functional role of the head domain we expressed N-terminally truncated
molecules using a cDNA coding for SF-assemblin from Chlamydomonas reinhardtii.
Recombinant wild-type SF-assemblin or molecules with an N-terminal deletion of
ten residues formed striated fibers with an axial repeat of 28 nm. N-terminal
truncations of 19 and 29 residues yielded assembly-incompetent molecules,
revealing that the head domain is necessary for the constitution of striated
fibers. Further, molecules with an internal deletion of 24 residues or with
duplicated segments corresponding to insertions of 29 and 58 residues were
constructed. The resulting fibers had altered cross-striation patterns and axial
repeats. The observed shifts in the axial repeat corresponded well to the number
of inserted or deleted residues, indicating a linear coherence between molecule
length and axial repeat. The heptad pattern of the rod domain of SF-assemblin is
regularly interrupted by skip residues. The removal of one or two skip residues
had no significant effect on the ultrastructure of the striated fibers.
Substitution of skip no. 2 with alanine resulted in a modified, asymmetric cross
striation pattern, indicating a polar architecture of the striated fibers. In
summary, various mutations of SF-assemblin effected the solubility of the
molecules, and the axial repeat, cross-striation pattern, or overall appearance
of the fibers. Thus, analysis of SF-assemblin may represent a valuable system to
study the interactions involved in the polymerization of fibrous coiled-coil
proteins. A model of the SMAFs based on staggered protofilaments consisting of
overlapping 36 nm subunits is presented.
PMID- 9642048
TI - Conformational changes of the Tet repressor induced by tetracycline trapping.
AB - The X-ray crystal structure analysis of inducer-free Tet repressor, TetR, at 2.4
A resolution identifies one of two openings of the tunnel-like binding site as
the entrance for the inducer tetracycline-Mg2+, [Mg Tc]+. Recognition and binding
of the inducer unleashes conformational changes leading to the induced state of
TetR. In the first step, the C-terminal turn of alpha-helix 6 unwinds, thereby
altering the orientation of alpha-helix 4. This different orientation of alpha
helix 4 is stabilized by a series of hydrogen bonds mediated through a chain of
eight water molecules. The alpha-helix 4 connects the DNA-binding domain (alpha
helices 1 to 3) to the rigid TetR core, and thus regulates gene expression
through its respective orientations.
PMID- 9642049
TI - Side-chain effects on peptidyl-prolyl cis/trans isomerisation.
AB - Peptidyl-prolyl cis/trans isomerisation has been frequently found as a rate
limiting step in the folding of proteins. In order to determine whether the
nature of the amino acid preceding proline controls the probability of cis prolyl
bonds in native proteins, systematic studies on the thermodynamics and kinetics
of the prolyl isomerisation in the pentapeptide series Ac-Ala-Xaa-Pro-Ala-Lys-NH2
were performed. All proteinogenic amino acids were substituted in the position
preceding proline. When measured by 1H-NMR and CD spectroscopy both isomers
proved to be devoid of ordered structure in the whole series of the oligopeptides
in aqueous solution. Thus, isomerization rates and cis/trans ratios calculated
from solvent jump and 1H-NMR magnetisation transfer experiments exclusively
reflect the side-chain effects of the Xaa position in the peptide series. There
is a rough correlation between the cis content in the oligopeptides and the
propensity of Xaa-Pro cis prolyl bonds in proteins. This correlation suggests
that the prolyl bond conformation is mainly determined by local effects in
proteins. The rate constants kc-->t of pentapeptides containing unionised amino
acids preceding proline range from 3.2 x 10(-3) s-1 (Xaa = Ala) to 0.5 x 10(-3) s
1 (Xaa = Trp) at 4 degrees C. Proline clustering led to an isomerisation cycle
indicating considerable influence on the isomerisation rates of the peptide bond
conformations flanking the rotating bond. Both tyrosine and histidine
specifically reduce isomerisation rates severalfold by deprotonation of their
respective side-chains.
PMID- 9642050
TI - The nature of ligand-induced conformational change in transferrin in solution. An
investigation using X-ray scattering, XAFS and site-directed mutants.
AB - Ligand-induced conformational change in transferrins has been studied by site
directed mutagenesis of human serum half molecule (N-lobe), X-ray absorption fine
structure (XAFS) spectroscopy and X-ray solution scattering. Use of recent
advances in data analysis has been made for extracting model-independent
molecular shapes from X-ray solution scattering data for the intact, the half
molecule and its mutants. Clear evidence is provided that the transferrin
molecule (intact as well as N-lobe), in its apo and holo forms, exists for the
majority of the time in well-defined specific conformations representing the
"fully opened" and "closed" states of the molecule, respectively. Evidence is
also provided for the existence of an additional conformation, referred to here
as the "intermediate" conformation for simplicity, which is trapped in the case
of some of the mutants in the iron-bound form. We suggest that domain closure in
the transferrin molecule is a two-step process, with the intermediate
conformation representing the first stage of domain closure (approximately 20
degrees hinge-twist of domain II). Our data are not inconsistent with the ligand
free molecule sampling the closed states occasionally (< or = 10%) but are not in
support of a continuous conformational search between the fully opened and closed
states in the absence of iron.
PMID- 9642051
TI - Structure-based redesign of the catalytic/metal binding site of Cfr10I
restriction endonuclease reveals importance of spatial rather than sequence
conservation of active centre residues.
AB - According to the crystal structure of Cfr10I restriction endonuclease the acidic
residues D134, E71 and E204 are clustered together and presumably chelate metal
ion(s) at the active site. Indeed, investigation of the DNA cleavage properties
of substitutional mutants of Cfr10I D134A, E71Q, E71A and E204Q reveals that
D134, E71 and E204 residues are essential for cleavage activity, supporting their
active site function. Structural comparison indicates that the D134 residue of
Cfr10I spatially overlaps with aspartate residues D91 and D74, from the invariant
active site motifs 90PDX19EAK and 73PDX15DIK of EcoRI and EcoRV, respectively.
However, structural studies in conjunction with mutational analyses suggest that
the sequence motif 133PDX55KX13E corresponds to the active site of Cfr10I, but
differs from canonical active site motifs of EcoRI and EcoRV. According to the
crystal structure of Cfr10I the serine S188 residue from the 188SVK sequence
motif is a spatial equivalent of the acidic residue from the (E/D)XK-part of the
active site motif, which is conserved between EcoRI and EcoRV. Site-directed
mutagenesis experiments of Cfr10I, however, revealed that the S188 was not so
important for catalysis while the E204 residue located 2.8 A away indeed was
essential for cleavage, suggesting that the glutamate E204 rather than the S188
residue contributes to the metal binding site in Cfr10I. In addition, model
building studies suggest that mutual interchange of the E204 and S188 residues
should lead only to minor positional differences of the carboxylate residues of
glutamate side-chains. The double mutant S188E/E204S was therefore prepared by
site-directed mutagenesis where the active site motif 133PDX55KX13E of Cfr10I was
changed to a canonical motif 133PDX53EVK, which is similar to that of EcoRI and
EcoRV. Interestingly, the double mutant S188E/E204S of Cfr10I with redesigned
active site structure, exhibited 10% of Wt cleavage activity in a gamma DNA
cleavage assay. Thus, structure guided redesign of the catalytic/metal binding
site of Cfr10I, provides novel experimental evidence to suggest that spatial
rather than sequence conservation plays the dominant role in the formation of
restriction enzyme active sites.
PMID- 9642052
TI - A partial hprt gene duplication generated by non-homologous recombination in V79
Chinese hamster cells is eliminated by homologous recombination.
AB - Here, the sequence in the hprt gene of the duplication mutant SPD8 originating
from V79 Chinese hamster cells was determined. The duplication arose after non
homologous recombination between exon 6 and intron 7, resulting in an extra copy
of the 3' portion of exon 6, of exon 7 and of flanking intron regions. Only a
duplication of exon 7 is present in the mRNA, since the duplicated exon 6 lacks
its 5' splice site and is removed during RNA processing. The findings in this
study suggest that the non-homologous recombination mechanism which occurred here
may have been initiated by endonucleases, rather than by a spontaneous double
strand break. Subsequently, 14 spontaneous SPD8 revertants with a functional hprt
gene were isolated and characterized using PCR and sequencing. The data revealed
that although the SPD8 cell line arose by non-homologous recombination, it
reverts spontaneously by homologous recombination. Interestingly, the downstream
copy of exon 7 was restored by this process. This was indicated by the presence
of a specific mutation, a T-to-G transversion, close to the breakpoint, a
characteristic unique to the SPD8 clone. Our results suggest that the spontaneous
reversion of this cell line by homologous recombination may involve an exchange,
rather than a conversion mechanism.
PMID- 9642053
TI - New insights for dinucleotide backbone binding in conserved C5'-H . . . O
hydrogen bonds.
AB - Most enzymes that utilize dinucleotide NAD or NADP are known to comprise a
glycine-rich loop segment (e.g. the GXGXXG signature motif of Rossman fold) which
binds the cofactor's diphosphate moiety. Through analysis of a set of diverse
NAD(P)-bound protein structures, we show here that with few exceptions this
diphosphate binding is complemented by a second loop segment interacting from a
different angle with unconventional yet apparently ubiquitous C-HellipsisO
hydrogen bonds formed between C5' methylene of dinucleotide and, primarily,
carbonyl oxygen of protein. This finding implicates an important role of C5' in
protein-nucleotide recognition.
PMID- 9642054
TI - Two large subunits of the fission yeast RNA polymerase II provide platforms for
the assembly of small subunits.
AB - The subunit-subunit contact network was analyzed for the Schizosaccharomyces
pombe RNA polymerase II consisting of ten putative subunits. Previously we
carried out far-Western blot analysis of bimolecular interaction with radio
labeled subunit 3 and 5 probes. Here we extended the analysis using another six
small-sized subunits as probes. Taking the results together the subunit-subunit
interaction was observed for a total 18 (or 19) combinations. All eight small
sized subunits exhibited binding activities to two large subunits, Rpb1 and Rpb2.
In addition, bimolecular interaction was observed for the combinations of Rpb3
Rpb5, Rpb3-Rpb11 (and Rpb5-Rpb8/11). The subunit-subunit contact within the
assembled RNA polymerase was then analyzed by protein-protein cross-linking using
five species of bifunctional cross-linkers with different length and specificity.
Cross-linking was observed for a total of 19 combinations, including five
combinations between small subunits, Rpb3-Rpb10, Rpb3-Rpb11, Rpb5-Rpb6, Rpb6-Rpb7
and Rpb6-Rpb8. The results altogether indicate that two large subunits Rpb1 and
Rpb2 provide the platform for assembly of small subunits and also small subunits
interact with each other for limited combinations. Direct contact of the two
large subunits, Rpb1 and Rpb2, was also demonstrated by cross-linking.
PMID- 9642055
TI - Effects of reaction conditions on RNA secondary structure and on the helicase
activity of Escherichia coli transcription termination factor Rho.
AB - The ATPase and helicase activities of the Escherichia coli transcription
termination protein rho have been studied under a variety of reaction conditions
that alter its transcription termination activity. These conditions include KCl,
KOAc, or KGlu concentrations from 50 to 150 mM and Mg(OAc)2 concentrations from 1
to 5 mM (in the presence of 1 mM ATP). In higher KCl or higher Mg(OAc)2
concentrations we found that the translocation of rho hexamers along RNA was
slower and less processive than the same process measured at 50 mM monovalent
salt concentrations and 1 mM Mg(OAc)2. The ATPase activity of rho was also
decreased under reaction conditions that slowed translocation. RNA melting
experiments showed that the decreased ATPase activity of rho and the slower
helicase activity at increased KCl or Mg(OAc)2 concentrations are accompanied by
a concomitant increase in the secondary structure of the RNA portion of the
helicase substate. In contrast, the ATPase activity of rho in the presence of
poly(rC), a synthetic RNA that does not form salt-concentration-dependent
secondary structure, was shown to be the same in each of the three monovalent
salts. Thus, the salts do not directly affect the structure or conformation of
the rho protein or the binding of rho to single-stranded RNA. However, the
translocation of rho along RNA was more processive in 150 mM KOAc or KGlu than in
150 mM KCl, while the RNA secondary structure was the same in all three
monovalent salts. Therefore, the monovalent salt present in the reaction may
directly affect rho-RNA interactions when the RNA substrate can form secondary
structure. Helicase experiments with an RNA molecule that does not contain a rho
loading-site showed that rho translocates less processively along this potential
helicase substrate. These results suggest that the helicase activity of rho may
be significantly regulated by RNA secondary structure. In addition, one of the
mechanisms to concentrate the activity of rho on transcripts containing
unstructured rho loading sites may be that rho translocation along such molecules
is more processive than it is along more structured RNA molecules in the cell.
PMID- 9642056
TI - tRNA imbalance promotes -1 frameshifting via near-cognate decoding.
AB - tRNAGly1 is the Escherichia coli glycine tRNA specific for GGG codons. A genetic
selection for multicopy suppressors of a frameshift mutation has shown that
increased levels of wild-type tRNAGly1 causes -1 frameshifting. Analysis of the
suppression spectrum of this multicopy suppressor and peptide sequencing of the
suppressed protein product showed that it promoted GG doublet decoding at the
near-cognate GGA codons. It is proposed that increasing the concentration of the
GGG-specific tRNAGly1 relative to the cognate GGA-decoding tRNAGly2 allows the
near-cognate tRNA to read GGA codons. Near-cognate decoding of GGA codons by
tRNAGly1 can occur by a two-out-of-three reading mechanism, in which only the
first two bases of the GGA codon are paired with the anticodon, thus permitting
doublet translocations. In mycoplasmas, a single tRNA typically decodes all four
triplets of a codon family and introduction of a feature of the Mypoplasma
mycoides tRNAGly responsible for non-discriminate decoding, a C at position 32,
into the anticodon E. coli tRNAGly1, enhanced the efficiency of doublet decoding.
PMID- 9642057
TI - A novel class of supercoil-independent nuclease hypersensitive site is comprised
of alternative DNA structures that flank eukaryotic genes.
AB - The cell makes a fundamental distinction between genes and non-gene sequences,
which mechanistically underlies the process of gene regulation. Here, we describe
the properties of a novel class of genetic sites that reproducibly flank and
delineate the coding regions of the eukaryotic genes tested. Defined in vitro
reaction conditions that include altered solvation and elevated temperature
rendered the sites hypersensitive to nuclease cleavage. Consequently, the
complete coding regions of the Drosophila genes tested were quantitatively
excised from genomic DNA or genomic clones by this treatment. Identical reaction
products were generated from linear or supercoiled DNA substrates. Chemical
modification and fine-structure analysis of several cleavage sites flanking
Drosophila genes showed that the cleavage sites were stable nucleic acid
structures that contained specific arrangements of paired and unpaired
nucleotides. The locations and properties of the cleavage sites did not
correspond to previously known nuclease hypersensitive sites nor to known
alternative DNA structures. Thus, they appear to represent a new class of genetic
site. In a deletion analysis, the minimal sequence information necessary to
direct in vitro nuclease cleavage 3' to the Drosophila GART gene co-localized
with the signal required for termination of transcription in vivo. The data
suggest that a novel class of DNA site with distinct structural properties
encodes biological information by marking the boundaries of at least some gene
expression units in organisms as diverse as Plasmodium and Drosophila.
PMID- 9642058
TI - A superrepressor mutant of the arginine repressor with a correctly predicted
alteration of ligand binding specificity.
AB - Arginine biosynthesis in Escherichia coli is negatively regulated by the
hexameric repressor protein ArgR and the corepressor L-arginine. L-Arginine binds
to ArgR in the C-terminal domain of the repressor. Binding to operator DNA occurs
in the N-terminal domain. The molecular structures of both domains have recently
been elucidated. The known stereochemistry of the arginine binding pocket was
used for the rational design of a mutant ArgR with altered ligand specificity.
Our prediction was that a replacement of Asp128 by asparagine would
preferentially lead to the binding of L-citrulline, rather than L-arginine. The
D128N mutant was constructed and was shown to fulfill our expectation by several
experimental approaches. By isothermal titration calorimetry it was found to bind
L-citrulline much more strongly than L-arginine, in contrast to wild-type ArgR.
Exchange between the mutant trimers of the hexamer was inhibited by L-citrulline,
as it is by L-arginine in the wild-type. The mutant protein was precipitated by L
citrulline but not by L-arginine, whereas the reverse is true for the wild-type
protein. Demonstration of a corepressor action was, however, precluded by the
superrepressor effect of the D128N mutation by itself. The mutant protein, in the
absence of L-citrulline or L-arginine is as strong a repressor as the wild-type
protein in the presence of L-arginine. We discuss two possible mechanisms, in
terms of the known domain structures that could explain our observations.
PMID- 9642059
TI - The transcriptional activator GvpE for the halobacterial gas vesicle genes
resembles a basic region leucine-zipper regulatory protein.
AB - The GvpE protein involved in the regulation of gas vesicles synthesis in
halophilic archaea has been identified as the transcriptional activator for the
promoter located upstream of the gvpA gene encoding the major gas vesicle
structural protein GvpA. A closer inspection of the GvpE protein sequence
revealed that GvpE resembles basic leucine-zipper proteins typically involved in
the gene regulation of eukarya. A molecular modelling study of the C-terminal
part implied a cluster of basic amino acid residues constituting the DNA-binding
site (DNAB) followed by an amphiphilic helix, suitable for the formation of a
leucine-zipper structure within a GvpE dimer. The model of a GvpE dimer docked
onto DNA indicated that the side-chains of the basic residues could perfectly
interact with the negatively charged phosphate groups of the DNA backbone.
Substitution of three basic amino acid residues of this putative DNAB by alanine
and/or glutamate generated mutated GvpE proteins. None of these was able to
activate the c-gvpA promoter in vivo, indicating that these basic residues are
required for GvpE activity. This identification of an archaeal gene regulator
displaying similarity to eukaryal regulatory proteins implies that the basic
transcription machinery of eukarya and archaea are closely related, and that the
regulatory proteins have evolved according to common principles.
PMID- 9642060
TI - Derivation of the three-dimensional architecture of bacterial ribonuclease P RNAs
from comparative sequence analysis.
AB - The secondary structure of bacterial RNase P RNA, a ribozyme responsible for the
maturation of the 5' end of tRNAs, is well established on the basis of sequence
comparison analysis. RNase P RNA secondary structures fall into two types, A and
B, which share a common core formed by the assembly of two main folding domains,
but differ in their peripheral elements.A revised alignment of 137 available
sequences reveals new covariations allowing for the refinement of both types of
secondary structures. Phylogenetic evidence is thus provided for the extension of
stems P11, P14, P19, P10.1 and P15.1 through further canonical base-pairs or
GAellipsisGA mismatches. These refinements led in turn to a new organization of
the catalytic core, with coaxial stackings of helices P2 and P19 as well as P1
and P4. New inter-domain tertiary interactions involve loop L9 and helix P1 and
loop L8 with helix P4. These features were incorporated into atomic-scale 3D
models of RNase P RNA for representatives of each structural type, namely
Escherichia coli and Bacillus subtilis. In each model, the juxtaposition of the
core helices creates a cradle onto which the pre-tRNA substrate binds with most
evolutionarily conserved residues converging towards the cleavage site. The inner
cores of both types are stabilized similarly, albeit by different peripheral
elements, emphasizing the modular and hierarchical organisation of the
architecture of RNase P RNAs. Similarities are thus apparent between the type A
modules, P16/P17/P6 and P13/P14, and their type B analogs, P5.1/P15.1 and P10.
1/P10.1a, respectively. Other noteworthy features of these models include
compactness and good agreement with published crosslinking data.
PMID- 9642061
TI - Branch migration through DNA sequence heterology.
AB - Branch migration of a DNA Holliday junction is a key step in genetic
recombination. Previously, it was shown that a single base-pair heterology
between two otherwise identical DNA sequences is a substantial barrier to passage
of a Holliday junction during spontaneous branch migration. Here, we exploit this
inhibitory effect of sequence heterology to estimate the step size of branch
migration. We also devise a simulation of branch migration through mismatched
base-pairs to arrive at the underlying molecular basis for the block to branch
migration imposed by sequence heterology. Based on the observation that two
adjacent sequence heterologies exert their effects on branch migration more or
less independently, we conclude that the step size of branch migration is quite
small, of the order of one or two base-pairs per migratory step. Comparison of
branch migration experiments through a single base-pair heterology with
simulations of a random walk through sequence heterology suggests that the
inhibition of branch migration is largely attributable to a thermodynamic barrier
arising from the formation of unpaired or mispaired bases in heteroduplex DNAs.
PMID- 9642062
TI - Mutational analysis of phi29 DNA polymerase residues acting as ssDNA ligands for
3'-5' exonucleolysis.
AB - Here, three highly conserved amino acid residues have been characterized to
function as ssDNA binding ligands at the 3'-5' exonuclease active site of phi29
DNA polymerase. One of these residues, Phe65, belongs to motif Exo II, previously
described to contain an invariant aspartate and an invariant asparagine involved
in catalysis and ssDNA binding, respectively. The other two residues, Ser122 and
Leu123, form a newly identified motif "(S/T)Lx2h", and are the homologous
counterparts of Pol I residues Asp457 and Met458, and of T4 DNA polymerase
residues Ser286 and Leu287, the latter three residues shown to contact ssDNA at
their corresponding cocrystal 3D structures. Site-directed mutagenesis and
biochemical analysis of eight phi29 DNA polymerase mutant proteins at residues
Phe65, Ser122 and Leu123 indicated their functional importance for: (1) a stable
interaction with ssDNA; (2) 3'-5' exonucleolysis of ssDNA substrates; (3)
proofreading of DNA polymerization errors. Extrapolation to the crystal
structures of Klenow and T4 DNA polymerases indicates that the invariant aromatic
ring contiguous to the catalytic aspartate of the Exo II motif, corresponding to
Tyr423 in Klenow, Phe218 in T4, and Phe65 in phi29 DNA polymerase, appears to be
critical to orient the ssDNA substrate in a stable conformation to allow 3'-5'
exonucleolytic catalysis. This is the first time that the functional importance
of this invariant residue, belonging to the Exo II motif, has been demonstrated.
PMID- 9642063
TI - Analyzing the functional organization of a novel restriction modification system,
the BcgI system.
AB - BcgI is a novel, multi-subunit, restriction-modification (R-M) system that
differs from all the other types of R-M system in its genetic and functional
organization. The holoenzyme contains two different subunits, BcgI A and BcgI B.
Both are required for endonuclease and methyltransferase activities. Here, we
show that the endonuclease activity is mediated by the N-terminal portion of the
A subunit. We made this assignment by mutational analysis. The analytic strategy
involved three steps. First, the methyltransferase activity was inactivated by
site-directed mutagenesis of a conserved methyltransferase motif also found in
the A subunit. One of the R+M- mutants could not methylate DNA but was still able
to cleave it, therefore expression of this mutant gene was lethal to the host.
This lethal phenotype allowed the selective isolation of cleavage-deficient (R-)
mutations in a second round of random mutagenesis in this mutant background. The
R- mutations were all located in the N-terminal portion of the A subunit. There
are five potential endonuclease motifs within this region. Conserved acidic
residues in each of these motifs were substituted with alanine by site-directed
mutagenesis of the wild-type A gene. The results identified one motif, P52E53
(X)12-E66D67K68, as the probable endonuclease active-site. Further support for
this assignment was obtained by another round of site-directed mutagenesis
directed to residues surrounding this motif. The results showed that DNA cleavage
activity was mediated by the predicted, conserved residues, and not any of the
surrounding non-conserved residues. One mutant protein, BcgI-E53A, with a single
amino acid substitution decreased the DNA cleavage activity at least 700-fold.
Our present model for the functional organization of BcgI locates both
endonuclease and methyltransferase domains in the A subunit, with the target
recognition domain located in the B subunit.
PMID- 9642064
TI - Catapult mechanism renders the chaperone action of Hsp70 unidirectional.
AB - Molecular chaperones of the Hsp70 type promote the folding and membrane
translocation of proteins. The interaction of Hsp70s with polypeptides is linked
to ATP binding and hydrolysis. We formed complexes of seven different
fluorescence-labeled peptides with DnaK, the Hsp70 homolog of Escherichia coli,
and determined the rate of peptide release under two different sets of
conditions. (1) Upon addition of ATP to nucleotide-free peptide.DnaK complexes,
all tested peptides were released with similar rate constants (2.2 s-1 to 6.7 s
1). (2) In the binding equilibrium of peptide and ATP-liganded DnaK, the
dissociation followed one or two-step reactions, depending on the amino acid
sequence of the peptide. For the monophasic reactions, the dissociation rate
constants diverged by four orders of magnitude from 0.0004 s-1 to 5.7 s-1; for
the biphasic reactions, the rate constants of the second, slower isomerization
step were in the range from 0.3 s-1 to 0.0005 s-1. The release of the different
peptides in case (1) is 1.4 to 14,000 times faster than in case (2). Apparently,
binding of ATP induces a transient state of the chaperone which ejects target
peptides before the final state of ATP-liganded DnaK is reached. This "catapult"
mechanism provides the chaperone cycle with a mode of peptide release that does
not correspond with the reverse of peptide binding. By allowing the conformation
of the outgoing polypeptide to differ from that of the incoming polypeptide, a
futile cycle with respect to conformational work exerted on the target protein is
obviated.
PMID- 9642065
TI - Functional properties of the molecular chaperone DnaK from Thermus thermophilus.
AB - The genes coding for the Thermus thermophilus (Tth) homologues of the molecular
chaperones DnaK and GrpE (DnaKTth and GrpETth) were cloned and expressed in
Escherichia coli. The proteins were purified and their functional properties were
assessed by equilibrium and transient kinetic methods. DnaKTth has an intrinsic
ATPase activity of 3x10(-4) s-1 at 25 degreesC and 10x10(-4) s-1 at 75 degreesC
under single turnover conditions. It binds the fluorescent nucleotide analogue N8
(4-N'-methylanthraniloylaminobutyl)-8-aminoadenosine 5'-diphosphate (MABA-ADP)
with a dissociation constant (Kd) of 3 nM and ADP with a Kd of 47 nM at 25
degreesC. At 75 degreesC the affinities are decreased fivefold to 15 nM (MABA
ADP) and 280 nM (ADP). The kinetic constants for two-step binding of MABA-ADP and
of ADP to DnaKTth were determined at 25 degreesC and 75 degreesC, respectively.
GrpETth acts as a nucleotide-exchange factor on DnaKTth and accelerates the
release of bound MABA-ADP significantly. This shows that the nucleotide-binding
domain is functionally intact, and that the specific interaction of DnaKTth and
GrpETth is mediating nucleotide exchange.A fluorescently labelled peptide that
comprises a subsequence of the E. coli transcription factor sigma32 binds to
nucleotide-free DnaKTth with a Kd of 4.9 microM. Displacement with unlabelled
peptide yields a Kd of 5.0 microM for the unlabelled peptide. Thus the peptide
binding domain also appears to be functional.For the cellular chaperone function
of DnaK, a coupling between nucleotide and peptide-binding domains is required.
However, with DnaKTth in the ATP as well as in the ADP.Pi-state, peptide is bound
and released within seconds. No correlation between ATP-binding or hydrolysis by
DnaKTth and changes in the sigma32 peptide exchange rates could be detected. It
thus appears that the DnaK system from Th. thermophilus has a different mechanism
of coupling the nucleotide state to the fast and slow peptide exchange
properties.
PMID- 9642066
TI - Purified lens major intrinsic protein (MIP) forms highly ordered tetragonal two
dimensional arrays by reconstitution.
AB - Lens major intrinsic protein (MIP) is the founding member of the MIP family of
membrane channel proteins. Its isolation from ovine lens fibre cell membranes and
its two-dimensional crystallization are described. Membranes were solubilized
with N-octyl-beta-D-glucoside and proteins fractionated by sucrose gradient
centrifugation containing decyl-beta-D-maltoside. MIP was purified by cation
exchange chromatography, and homogeneity was assessed by mass analysis in the
scanning transmission electron microscope. Purified MIP reconstituted into a
lipid bilayer at a low lipid-to-protein ratio formed highly ordered tetragonal
two-dimensional crystals. The square unit cell had a side length of 6.4 nm, and
exhibited in negative stain four stain-excluding elongated domains surrounding a
central stain-filled depression. Projection maps of freeze-dried crystals
exhibited a resolution of 9 A, and revealed a monomer structure of MIP consisting
of distinct densities. Despite significant differences in the packing of
tetramers in the crystals, the projection map of the MIP monomer was similar to
that of aquaporin-1 (AQP1), the first member of the MIP family which had its
structure resolved to 6 A. Our protocols for the purification and reconstitution
of MIP establish the feasibility for future work to visualize structure elements
which determine the diverse functional properties of the MIP family members.
PMID- 9642067
TI - Role of the C-terminal tryptophan residue for the structure-function of the
alphavirus capsid protein.
AB - The Semliki Forest virus capsid protein is a multifunctional protein which
packages genomic RNA into nucleocapsid structures and binds to viral spike
protein during budding. In addition, the capsid protein has an autoproteolytic
activity whereby the C-terminal tryptophan is used as the substrate for
cotranslational cleavage of the viral structure polyprotein. The autoproteolytic
domain of the capsid protein has a chymotrypsin-like fold but has two additional
short beta-strands which place the tryptophan into the active site. Here, we have
substituted the C-terminal tryptophan of Semliki Forest virus capsid protein for
alanine, arginine and phenylalanine and analysed the effects on different
functions of the C protein such as nucleocapsid formation, spike binding and
autoproteolytic activity. We found that (i) tryptophan is a better substrate for
the autoproteolytic activity, (ii) the wild-type tryptophan is the only residue
that allows efficient viral growth and (iii) an aromatic residue is important for
correct initial folding and stability of the protein.
PMID- 9642068
TI - Ribosomal proteins S5 and L6: high-resolution crystal structures and roles in
protein synthesis and antibiotic resistance.
AB - Antibiotic resistance is rapidly becoming a major medical problem. Many
antibiotics are directed against bacterial ribosomes, and mutations within both
the RNA and protein components can render them ineffective. It is well known that
the majority of these antibiotics act by binding to the ribosomal RNA, and it is
of interest to understand how mutations in the ribosomal proteins can produce
resistance. Translational accuracy is one important target of antibiotics, and a
number of ribosomal protein mutations in Escherichia coli are known to modulate
the proofreading mechanism of the ribosome. Here we describe the high-resolution
structures of two such ribosomal proteins and characterize these mutations. The
S5 protein, from the small ribosomal unit, is associated with two types of
mutations: those that reduce translational fidelity and others that produce
resistance to the antibiotic spectinomycin. The L6 protein, from the large
subunit, has mutations that cause resistance to several aminoglycoside
antibiotics, notably gentamicin. In both proteins, the mutations occur within
their putative RNA-binding sites. The L6 mutations are particularly drastic
because they result in large deletions of an RNA-binding region. These results
support the hypothesis that the mutations create local distortions of the
catalytic RNA component.When combined with a variety of structural and
biochemical data, these mutations also become important probes of the
architecture and function of the translational machinery. We propose that the C
terminal half of S5, which contains the accuracy mutations, organizes RNA
structures associated with the decoding region, and the N-terminal half, which
contains the spectinomycin-resistance mutations, directly interacts with an RNA
helix that binds this antibiotic. As regards L6, we suggest that the mutations
indirectly affect proofreading by locally distorting the EF-Tu.GTP.aminoacyl tRNA
binding site on the large subunit.
PMID- 9642069
TI - Structural investigation of the cofactor-free chloroperoxidases.
AB - The structures of cofactor-free haloperoxidases from Streptomyces aureofaciens,
Streptomyces lividans, and Pseudomonas fluorescens have been determined at
resolutions between 1.9 A and 1.5 A. The structures of two enzymes complexed with
benzoate or propionate identify the binding site for the organic acids which are
required for the haloperoxidase activity. Based on these complexes and on the
structure of an inactive variant, a reaction mechanism is proposed for the
halogenation reaction with peroxoacid and hypohalous acid as reaction
intermediates. Comparison of the structures suggests that a specific halide
binding site is absent in the enzymes but that hydrophobic organic compounds may
fit into the active site pocket for halogenation at preferential sites.
PMID- 9642070
TI - Three-dimensional structures of single-chain Fv-neuraminidase complexes.
AB - The structure of the complex between a recombinant single-chain Fv construct of
antibody NC10 with a five-residue peptide linker between VH and VL (termed
scFv(5)), and its antigen, tetrameric neuraminidase from influenza virus (NA),
has been determined and refined at 2.5 A resolution. The antibody-antigen binding
interface is very similar to that of a similar NC10 scFv-NA complex in which the
scFv has a 15-residue peptide linker (scFv(15)), and the NC10 Fab-NA complex.
However, scFv(5) and scFv(15) have different stoichiometries in solution. While
scFv(15) is predominantly monomeric in solution, scFv(5) forms dimers
exclusively, because the five-residue linker is not long enough to permit VH and
VL domains from the same polypeptide associating and forming an antigen-binding
site. Upon forming a complex with NA, scFv(15) forms a approximately 300 kDa
complex corresponding to one NA tetramer binding four scFv(15) monomers, while
scFv(5) forms a approximately 590 kDa complex, corresponding to two NA tetramers
crosslinked by four bivalent scFv(5) dimers. However, the dimeric scFv(5) in the
scFv(5)-NA crystals does not crosslink NA tetramers, and modelling studies
indicate that it is not possible to pack four dimeric and simultaneously bivalent
scFvs between the NA tetramers with only a five-residue linker between VH and VL.
The inability arises from the exacting requirement to orient the two antigen
binding surfaces to bind the tetrameric NA antigen while avoiding steric clashes
with NC10 scFv(5) dimers bound to other sites on the NA tetramer. The utility of
bivalent or bifunctional scFvs with short linkers may therefore be restricted by
the steric constraints imposed by binding multivalent antigens.
PMID- 9642071
TI - Solution structure and dynamics of the bioactive retroviral M domain from Rous
sarcoma virus.
AB - A biologically active construct of the retroviral M domain from the avian Rous
sarcoma virus is defined and its solution structure described. This M domain is
fully active in budding and infectivity without myristylation. In spite of a
sequence homology level that suggests no relationship among M domains and the
family of matrix proteins in mammalian retroviruses, the conserved structural
elements of a central core allow an M domain sequence motif to be described for
all retroviruses. The surface of the M domain has a highly clustered positive
patch comprised of sequentially distant residues. An analysis of the backbone
dynamics, incorporating rotational anisotropy, is used to estimate the
thermodynamics of proposed domain oligomerization.
PMID- 9642072
TI - A disorder-to-order transition coupled to DNA binding in the essential zinc
finger DNA-binding domain of yeast ADR1.
AB - The motional dynamics and solvent-exchange behavior of free and DNA-bound forms
of the minimal zinc-finger DNA-binding domain of the yeast transcription factor
ADR1 (ADR1-DBD) are investigated using NMR. The parameters measured include the
1H-15N heteronuclear NOE, 15N and 1H T1 relaxation rates, 15N T2 relaxation
rates, and solvent-exchange rates. The spin relaxation parameters, spectral
density maps, and solvent-exchange behavior show that, exclusive of the N and C
termini, three distinct regions of free ADR1-DBD exhibit different motions on
multiple timescales. The N-terminal proximal, or accessory, region appears to be
unstructured and highly flexible: it exhibits large amplitude motions on a
picosecond timescale, little or no protection from solvent exchange, and random
coil proton chemical shifts. The two zinc fingers tumble anisotropically as
folded domains, with the tumbling of the individual fingers being only partly
correlated to each other, and are modestly protected from solvent exchange except
near the tips of the fingers and in the linker joining them. Free ADR1-DBD
exhibits exchange broadening around P97 in the proximal region, at the tip of
finger 1, and throughout finger 2. Upon binding, most of the proximal region and
both zinc fingers tumble as a single domain and exhibit significantly reduced
picosecond timescale motions. This region becomes more protected from solvent
exchange. The bound portion of the proximal region is proposed to lie exposed on
the surface of the DNA. Exchange broadening remains around P97 but also becomes
evident for residues in direct contact with the DNA and in the linker. We
conclude that the region of ADR1-DBD essential for high-affinity binding
undergoes a disorder-to-order transition upon binding to its cognate DNA and,
together with the zinc fingers, forms a cohesive molecular complex with the
nucleic acid.
PMID- 9642073
TI - Ecotin: a serine protease inhibitor with two distinct and interacting binding
sites.
AB - The interaction between ecotin and target proteases with trypsin-like specificity
has been systematically dissected to understand the structural basis of ecotin's
broad inhibitory specificity and the role of the secondary binding site. Site
directed and region-specific mutagenesis were preformed at ecotin's primary site
P1 residue (84), the C-terminal dimer interface (133 to 142), and two surface
loops of the secondary binding site (67 to 70, 108 to 113). Substitutions at the
P1 position resulted in less than fivefold difference in the potency of ecotin
binding to rat trypsin, suggesting that the extended binding site is important in
binding. A ten amino acid C-terminal truncation variant showed threefold weaker
self-association but remained a dimer. The interactions of the secondary binding
site of ecotin with bovine trypsin, rat trypsin and human urokinase-type
plasminogen activator (uPA) were investigated with alanine substitutions in
ecotin at Trp67, Gly68, Tyr69, Asp70, Arg108, Asn110, Lys112 and Leu113, which
formed contacts between the inhibitor and protease. By combining these mutations
at the secondary binding site with mutations in the primary binding site the
molecular recognition between ecotin and its target serine proteases was probed.
The contrast in the Ki values of the various ecotin variants towards bovine
trypsin, rat trypsin and human uPA established the role of ecotin's secondary
binding site in recognizing these homologous serine proteases. Ecotin binds to
proteases with a chymotrypsin fold through a combination of primary and secondary
site surface loops and is amenable to redesign of its potency and specificity for
this class of enzymes.
PMID- 9642074
TI - Inter-helical interactions in the leucine zipper coiled coil dimer: pH and salt
dependence of coupling energy between charged amino acids.
AB - We have investigated the physical nature of the observed coupling energy (Delta
Delta DeltaGint) between the charged side-chains of the three inter-helical g<-
>e' (i, i'+5) pairs (E<-->R, E<-->K, and E<-->E) in the leucine zipper coiled
coil dimer. Circular dichroism (CD) spectroscopy measured the thermal stability
of eight proteins derived from the basic region leucine zipper domain of chicken
VBP, the mammalian TEF at seven pHs and three KCl concentrations. Data from these
proteins were used to construct double mutant alanine thermodynamic cycles and
determine coupling energies (Delta Delta DeltaGint) for the three g<-->e' pairs.
The attractive E<-->R coupling energy of -0.6 kcal mol-1 at low salt decreases to
-0.2 kcal mol-1 at high salt. The E<-->K coupling energy of -0.5 kcal mol-1 at
low salt decreases to -0.1 kcal mol-1 at high salt. The repulsive E<-->E coupling
energy of +0.8 kcal mol-1 at low salt drops to +0.4 at high salt. Reducing the pH
to 2.2 halved the attractive coupling energy for the E<-->R and E<-->K pairs
while abolishing the repulsion of the E<-->E pair. 13C NMR of a protein
selectively labeled with [13Cdelta]glutamate that contained three E<-->R and one
R<-->E pair identified four glutamates shifted upfield. We suggest that this is
due to electronic perturbation of glutamates in inter-helical E<-->R
interactions. Taken together, these data indicate that the E<-->R coupling energy
of -0.5 kcal mol-1 at pH 7.4 and 150 mM KCl has an electrostatic component.
PMID- 9642075
TI - Design, synthesis and structure of a zinc finger with an artificial beta-turn.
AB - We have incorporated a bicyclic beta-turn mimetic (BTD; beta-turn dipeptide) into
a zinc finger, creating a zinc finger with an artificial beta-turn. The designed
peptide chelates zinc and has the same fold as the unmodified native zinc finger
(finger 3 of the human YY1 protein). A combination of 1H NMR and structure
calculations reveals that, in solution, this zinc finger has a fold similar to
the known wild-type crystal structure and to other zinc fingers containing the
consensus sequence X3-Cys-X4-Cys-X12-His-X3-His-X. The peptide was designed with
BTD between the chelating cysteine residues, with BTD forming a type II' beta
turn linking the two strands of a distorted anti-parallel beta-sheet. The C
terminal portion of the peptide forms a helix with zinc co-ordinating histidine
residues on successive turns of the helix. This work represents a step towards
developing methods by which parts of a target protein may be replaced by peptide
mimetics.
PMID- 9642076
TI - Dimer-to-tetramer transformation: loop excision dramatically alters structure and
stability of the ROP four alpha-helix bundle protein.
AB - The ROP loop excision mutant RM6 shows dramatic changes in structure and
stability in comparison to the wild-type protein. Removal of the five amino acids
(Asp30, Ala31, Asp32, Glu33, Gln34) from the loop results in a complete
reorganization of the protein as evidenced by single crystal X-ray analysis and
thermodynamic unfolding studies. The homodimeric four-alpha-helix motif of the
wild-type structure is given up. Instead a homotetrameric four-alpha-helix
structure with extended, loop-free helical monomers is formed. This intriguing
structural change is associated with the acquisition of hyperthermophilic
stability. This is evident in the shift in transition temperature from 71
degreesC characteristic of the wild-type protein to 101 degreesC for RM6.
Accordingly the Gibbs energy of unfolding is increased from 71.7 kJ (mol of
dimer)-1 to 195.1 kJ (mol of tetramer)-1. The tetramer-to-monomer transition
proceeds highly cooperatively involving an enthalpy change of DeltaH=1073+/-30 kJ
(mol of tetramer)-1 and a heat capacity change at the transition temperature of
DeltaDNCp=14.9(+/-)3% kJ (mol of tetramerxK)-1. The two-state nature of the
unfolding reaction is reflected in coinciding calorimetric and van't Hoff
enthalpy values.
PMID- 9642077
TI - Engineering bidentate macromolecular inhibitors for trypsin and urokinase-type
plasminogen activator.
AB - Ecotin, a dimeric serine protease inhibitor from Escherichia coli, is a novel
platform for inhibitor design. An approach using the three-dimensional structure
of the ecotin-trypsin complex to guide combinatiorial design efforts was taken to
create potent bidentate ecotin inhibitors for trypsin and human urokinase-type
plasminogen activator (uPA). The ecotin surface loop that was redesigned is
composed of residues 67 to 70 (60 s loop), and binds to the target protease at a
region 25 A from the enzyme active site. Two ecotin phage display libraries were
constructed to exploit the binding interactions at the 60 s loop. The ecotin 60X4
library, in which residues 67 to 70 of ecotin were randomized, was panned against
rat and bovine trypsin in parallel for four rounds. Panning against bovine
trypsin resulted in enrichment of ecotin phage but did not yield a consensus
sequence. Panning against rat trypsin resulted in enrichment as well as the
ecotin consensus sequence WGFP at positions 67 to 70. The variant ecotin encoded
by this sequence inhibited rat trypsin at 80 pM, a 12-fold improvement over
ecotin wild-type (WT). A second generation library, ecotin M84R+60X4 including an
additional methionine to arginine substitution at position 84 in the primary
binding site of ecotin, was generated for panning against uPA and rat trypsin.
Panning against rat trypsin resulted in enrichment but no consensus sequence.
Panning against uPA resulted in enrichment as well as the different ecotin
consensus sequence WGYR at positions 67 to 70. Ecotin M84R+D70R bound to uPA at
50 pM, a 56,000-fold increase in binding compared to ecotin WT. Furthermore,
ecotin M84R+D70R achieved a 13,680-fold preference of specificity towards uPA
versus rat trypsin. The fact that the 60 s loop of ecotin plays different roles
in binding to trypsin and uPA suggests this site can be used to introduce
specificity and potency for other members of the serine proteases with a
chymotrypsin fold.
PMID- 9642079
TI - Apologia
PMID- 9642078
TI - Structural basis for the high affinity of amino-aromatic SH2 phosphopeptide
ligands.
AB - An anthranyl moiety placed at the N terminus of a phosphotyrosine peptide
potentiates the inhibitory effect of this small peptide on the binding of the
Grb2 SH2 domain to the EGF receptor. Using molecular modeling procedures based on
the Lck SH2 domain structure, this observation was rationalized in terms of a
suitably favorable pi-pi stacking interaction between the anthranyl moiety and
the arginine alphaA2 (ArgalphaA2) residue side-chain of Grb2 SH2. The crystal
structure of the Grb2 SH2 domain in complex with the inhibitor 2-Abz-EpYINQ-NH2
(IC50 26 nM) has been solved in two different crystal forms at 2.1 and 1.8 A
resolution. This structure confirms the modeling based on the Lck SH2 domain. The
ArgalphaA2 residue is conserved in most SH2 domains. Thus, as expected, the
anthranyl group also confers high affinity to small peptide ligands of other SH2
domains such as Lck-, PLC-gamma-amino-terminal and p85 amino-terminal SH2 domains
as demonstrated by structure affinity relationships (SAR) data. These potent
peptides with an amino-terminal surrogate group and the structure of Grb2 SH2
domain in complex with one such peptide represent good starting points for the
design and optimization of new inhibitors of many SH2 domains.
PMID- 9642080
TI - Corrigendum
PMID- 9642081
TI - DNA microloops and microdomains: a general mechanism for transcription activation
by torsional transmission.
AB - Prokaryotic transcriptional activation often involves the formation of DNA
microloops upstream of the polymerase binding site. There is substantial evidence
that these microloops function to bring activator and polymerase into close
spatial proximity. However additional functions are suggested by the ability of
certain activators, of which FIS is the best characterised example, to facilitate
polymerase binding, promoter opening and polymerase escape. We review here the
evidence for the concept that the topology of the microloop formed by such
activators is tightly coupled to the structural transitions in DNA mediated by
RNA polymerase. In this process, which we term torsional transmission, a major
function of the activator is to act as a local topological homeostat. We argue
that the same mechanism may also be employed in site-specific DNA inversion.
PMID- 9642082
TI - Tyrosine phosphorylation in Escherichia coli.
AB - The phosphorylation on tyrosine of a protein in Escherichia coli both in vivo and
in vitro was revealed by recognition by anti-phosphotyrosine antibodies,
labelling with [gamma-32P]ATP, and phosphoamino acid analysis. This protein,
which we name TypA, is the product of the o591 reading frame as revealed by N
terminal sequencing and antibody cross-reactivity. Inactivation of typA altered
the patterns of protein synthesis during both exponential growth and carbon
starvation. These alterations included the disappearance of an acidic isoform of
both the universal stress protein UspA and carbon starvation protein Csp15, and
increased synthesis of the histone-like protein H-NS. The sequence of TypA from
strain K-12 differs from that of an enteropathogenic strain in six amino acid
residues and the protein is three residues shorter. We propose that TypA
interacts with global regulatory networks and that its phosphorylation may be
relevant to pathogenesis.
PMID- 9642083
TI - Unusual domain pairing in a mutant of bovine lens gammaB-crystallin.
AB - beta gamma-Crystallins from the eye lens are proteins consisting of two domains
joined by a short linker. All 3D structures solved so far reveal a similar pseudo
2-fold pairing of the domains, reflecting their presumed ancient origin from a
single-domain homodimer. Here we report the 2.2 A X-ray structure of the N
terminal domain of gammaB-crystallin, bearing a mutation of a residue involved in
domain contacts in the native molecule (Phe56Ala). It forms a crystallographic
homodimer, yet the domain orientation is different from native beta gamma
crystallins. It is considered that the new orientation derives from two
structural features. (1) The replacement of the bulky phenylalanine 56 by an
alanine results in a different optimal hydrophobic packing of interface residues
between identical domains. (2) The paired domains have extensions derived from
the domain linker, each containing a proline conserved in gamma-crystallins, and
the resulting steric constraints preclude a native-like pairing but support the
new arrangement. These data highlight the pivotal role of interface residues and
sequence extensions in overall domain assembly.
PMID- 9642084
TI - Reconstitution of the degradation of the mRNA for ribosomal protein S20 with
purified enzymes.
AB - Previous work has implicated poly(A) polymerase I (PAP I), encoded by the pcnB
gene, in the decay of a number of RNAs from Escherichia coli. We show here that
PAP I does not promote the initiation of decay of the rpsT mRNA encoding
ribosomal protein S20 in vivo; however, it does facilitate the degradation of
highly folded degradative intermediates by polynucleotide phosphorylase. As
expected, purified degradosomes, a multi-protein complex containing, among
others, RNase E, PNPase, and RhlB, generate an authentic 147-residue RNase E
cleavage product from the rpsT mRNA in vitro. However, degradosomes are unable to
degrade the 147-residue fragment in the presence of ATP even when it is
oligoadenylated. Rather, both continuous cycles of polyadenylation and PNPase
activity are necessary and sufficient for the complete decay of the 147-residue
fragment in a process which can be antagonized by the action of RNase II.
Moreover, both ATP and a non-hydrolyzable analog, ATPgammaS, support the PAP I
and PNPase-dependent degradation of the 147-residue intermediate implying that
ATPase activity, such as that which may reside in RhlB, a putative RNA helicase,
is not necessarily required. Alternatively, the rpsT mRNA can be degraded in
vitro by a second 3'-decay pathway which is dependent on PAP I, PNPase and ATP
alone. Our results demonstrate that a hierarchy of RNA secondary structures
controls access to exonucleolytic attack on 3' termini. Moreover, decay of a
model mRNA can be reconstituted in vitro by a small number of purified components
in a process which is more dynamic and ATP-dependent than previously imagined.
PMID- 9642085
TI - Cooperative interaction between the DNA-binding domains of PU.1 and IRF4.
AB - The two lymphoid-specific transcription factors PU.1 and IRF4 form a cooperative
ternary complex at immunoglobulin enhancer elements such as the lambdaB and
kappaE3' sites. We report here that the synergy of this interaction can be
reconstituted in part with the DNA-binding domains of the two proteins. The
minimal DNA binding-domain of IRF4 was mapped to residues 20 to 137,
corresponding to the conserved DNA-binding region of other interferon regulatory
factors (IRFs). This domain can bind weakly to a synthetic murine lambdaB
element, while IRF4 constructs that contain residues 1 to 19 require the presence
of PU.1 for DNA-binding at similar concentrations. Fluorescence polarization of
fluorescein-labelled DNA was used to show that the presence of residues 1 to 19
decreases the binding affinity of IRF4 N-terminal constructs from two- to
fivefold. However, all constructs bound better to the lambdaB element in the
presence of the DNA-binding domain of PU.1. This cooperative interaction was not
dependent on phosphorylation of the PEST domain of PU.1, but was dependent on the
proper spacing of the binding sites for PU.1 and IRF4. These data suggest that at
least part of the cooperative interaction between full-length PU.1 and IRF4
involves the DNA-binding domains of the two proteins. NMR spectroscopy of 15N
labelled PU.1 and IRF4 constructs indicates that the PEST domain of PU.1 and
residues 1 to 19 of IRF4 may be unstructured in the isolated proteins.
PMID- 9642086
TI - An Arg/Lys-rich core peptide mimics TRBP binding to the HIV-1 TAR RNA upper
stem/loop.
AB - TRBP is a cellular protein that binds to the HIV-1 leader RNA, TAR. Circular
dichroism experiments have shown that a 24 amino acid peptide (TR1), located
within a dsRNA binding domain (dsRBD) of TRBP, binds TAR with a 3:1
stoichiometry, eliciting a conformational change involving base unstacking. The
binding characteristics of synthetic structural variants of TAR indicate that
guanine residues play a key role in the TR1-RNA interaction and that binding
sites exist in the upper-stem/loop and lower stem region of TAR. Deletion
analysis of TR1 has led to the identification of a 15 amino acid subpeptide
(TR13) which is necessary and sufficient to bind to the high affinity upper
stem/loop binding site of TAR. Alanine scanning of TR13 has revealed that
mutations in either Lys or Arg residues result in altered TAR-binding, and
molecular modelling/docking experiments have shown that the two Arg residues of
TR13 can interact with two appropriately spaced guanine residues in the upper
stem/loop of TAR. The TR13 lysine residues appear to be essential for maintaining
structural integrity and the correct positioning of the Arg side-chains. We
propose that TRBP binds TAR by means of a "2-G hook" motif and that the binding
specificity of this particular member of the family of double-stranded RNA
binding proteins lies within the highly conserved dsRBD core motif. Finally, our
results also suggest that TRBP may function in vivo by modifying the tertiary
structure of TAR RNA.
PMID- 9642087
TI - Expansion of CTG repeats from human disease genes is dependent upon replication
mechanisms in Escherichia coli: the effect of long patch mismatch repair
revisited.
AB - Many human hereditary disease genes have been recently associated with the
expansion of CTG/GAC repeats. We have used a plasmid-based assay in Escherichia
coli to investigate the instability of a (CTG/GAC) insert containing 64 repeats.
Using this assay, expansions were biochemically detected and subsequently
quantified. We show that the occurence of expansions within these trinucleotide
repeats is dependent upon replicative mechanisms. Expansions of up to 30 repeats
and deletions of almost all possible sizes occured regardless of the orientation
of the insert relative to the replication origin. In contradiction to a previous
report, the mismatch repair pathway was found to strongly stabilize these repeat
stretches.
PMID- 9642088
TI - Hepatitis B virus capsid: localization of the putative immunodominant loop
(residues 78 to 83) on the capsid surface, and implications for the distinction
between c and e-antigens.
AB - Hepatitis B virus capsid protein comprises a 149 residue "assembly" domain that
polymerizes into icosahedral particles, and a 34 residue RNA-binding "protamine"
domain. Recently, the capsid structure has been studied to resolutions below 10 A
by cryo-electron microscopy, revealing much of its alpha-helical substructure and
that it appears to have a novel fold for a capsid protein; however, the
resolution is still too low for chain-tracing by conventional criteria. Aiming to
establish a fiducial marker to aid in the process of chain-tracing, we have used
cryo-microscopy to pinpoint the binding site of a monoclonal antibody that
recognizes the peptide from residues 78 to 83. This epitope resides on the outer
rim of the 30 A long spikes that protrude from the capsid shell. These spikes are
four-helix bundles formed by the pairing of helix-turn-helix motifs from two
subunits; by means of a tilting experiment, we have determined that this bundle
is right-handed. Variants of the same protein present two clinically important
and non-crossreactive antigens: core antigen (HBcAg), which appears early in
infection as assembled capsids; and the sentinel e-antigen (HBeAg), a non
particulate form. Knowledge of the binding site of our anti-HBcAg antibody bears
on the molecular basis of the distinction between the two antigens, which appears
to reflect conformational differences between the assembled and unassembled
states of the capsid protein dimer, in addition to epitope masking in capsids.
PMID- 9642089
TI - On the potential role of the amino nitrogen atom as a hydrogen bond acceptor in
macromolecules.
AB - Crystallographic studies of duplex DNA have indicated that opposing exocyclic
amino groups may form close NH⋯:N contacts. To study the nature of such
interactions, we have examined the database of small molecule, high-resolution
crystal structures for more accurate examples of this type of unconventional
interaction. We have found cases where the amino groups in guanine and adenine
bases accept hydrogen bonds from conventional donors, such as amino or hydroxyl
groups. More frequently, the purine amino group was found to contact closely
electropositive C-H groups. Searches of the nucleic acid structural databases
also yielded several examples where the purine amino group is contacted by
hydrogen bond donors in macromolecules. Ab initio calculations indicate that the
hydrogen-amino contact is improved energetically when the amino group moves from
the conventional geometry, where all atoms are co-planar with the base, to one in
which the hydrogen atoms lie out of the plane and the nitrogen is at the apex of
a pyramid, resulting in polarization of the amino group. The combined structural
and theoretical data suggest that the amino group is flexible, and can
accommodate close contacts, because the resulting polarization permits
electropositive atoms to approach the amino group nitrogen more closely than
expected for their conventional van der Waals radii. The flexibility of the amino
group may permit particular DNA conformations that enforce hydrogen-amino
contacts to optimize favorable stacking interactions, and it may play a role in
the recognition of nucleosides. We speculate that the amino group can accept
hydrogen bonds under special circumstances in macromolecules, and that this
ability might play a mechanistic role in catalytic processes such as deamination
or amino transfer.
PMID- 9642090
TI - A bisubstrate analog induces unexpected conformational changes in
phosphoglycerate kinase from Trypanosoma brucei.
AB - The glycolytic enzyme phosphoglycerate kinase (PGK) catalyzes phosphoryl transfer
between 1,3-bis-phosphoglycerate and ADP to form 3-phosphoglycerate and ATP.
During catalysis, a major hinge bending motion occurs which brings the N and C
terminal enzyme domains and their bound substrates together and in-line for
phosphoryl transfer. We have crystallized Trypanosoma brucei PGK in the presence
of the bisubstrate analog, adenylyl 1,1,5,5-tetrafluoropentane-1, 5
bisphosphonate, and solved the structure of this complex in two different crystal
forms at 1.6 and 2.0 A resolution, obtained from PEG 8000 and ammonium phosphate
solutions, respectively. These high resolution structures of PGK:inhibitor
complexes are of particular interest for drug design since Trypanosoma brucei,
the causative agent of African sleeping sickness, relies on glycolysis as its
sole energy source. In both structures, the inhibitor is bound in a fully
extended conformation with its adenosine moiety assuming exactly the same
position as in ADP:PGK complexes and with its 5' phosphonate group occupying part
of the 1,3-bis-phosphoglycerate binding site. The bisubstrate analog forces PGK
to assume a novel, "inhibited" conformation, intermediate in hinge angle between
the native structures of open and closed form PGK. These structures of enzyme
inhibitor complexes demonstrate that PGK has two distinct hinge points that can
each be independently activated. In the "PEG" structure, the C-terminal hinge is
partially activated while the N-terminal hinge point remains in an open state. In
the "phosphate" structure, closure of the N-terminal hinge point is also evident.
Finally and most unexpectedly, both complex structures also contain a 3 A shift
of a helix that lies outside the flexible hinge region. We propose that a
transient shift of this helix is a required element of PGK hinge closure during
catalysis.
PMID- 9642091
TI - Backbone dynamics of the EGF-like domain of heregulin-alpha.
AB - The backbone dynamics of the 63 residue epidermal growth factor (EGF)-like domain
of heregulin-alpha (HRG-alpha) have been characterized by measurement of
longitudinal relaxation rate constants (R1), transverse relaxation rate constants
(R2), and steady-state ?1H?-15N nuclear Overhauser effects for the 15N nuclear
spins using proton-detected heteronuclear NMR spectroscopy. Analysis of the R2/R1
ratios in conjunction with the known structure of the HRG-alpha EGF-like domain
yields a rotational correlation time of approximately 8.4 ns, suggesting that the
protein aggregates under the solution conditions used (3.8 mM protein, 50 mM
sodium acetate, pH 4.5, 20 degreesC), and that it tumbles with an axially
symmetric diffusion tensor (D parallel/D perpendicular=1.4). Sedimentation
equilibrium experiments confirm that the EGF-like domain of HRG-alpha undergoes
weak self-association under these conditions and are consistent with a simple
monomer-dimer equilibrium with a dimer-dissociation constant Kd=1.6(+/-0.4) mM.
The relaxation data were analyzed using a reduced spectral density mapping
approach to avoid systematic effects of aggregation on the usual model-free
formalism. The reduced spectral densities show that residues near the N terminus
(residues 3 to 5 and 7 to 12), in the Omega-loop between beta-strands 2 and 3
(residues 24 to 31), and in particular the C-terminal 13 residues (residues 51 to
63), have significant mobility on a picosecond/nanosecond time-scale. In
addition, conformational exchange on a microsecond time-scale was identified for
residues 44 to 46 on the basis of observed differences in R2 at 11.7 and 14.1 T.
The mobility identified near the N terminus and in the vicinity of residues 44 to
46 may be important in allowing the interactions of heregulin with multiple
receptors.
PMID- 9642092
TI - Exploring the folding pathways of annexin I, a multidomain protein. I. non-native
structures stabilize the partially folded state of the isolated domain 2 of
annexin I.
AB - Proteins of the annexin family constitute very attractive models because of their
four approximately 70 residue domains, D1 to D4, exhibiting an identical topology
comprising five helix segments with only a limited sequence homology of
approximately 30%. We focus on the isolated D2 domain, which is only partially
folded. A detailed analysis of this equilibrium partially folded state in aqueous
solution and micellar solution using 15N-1H multidimensional NMR is presented.
Comparison of the residual structure of the entire domain with that of shorter
fragments indicates the presence of long-range transient hydrophobic interactions
that slightly stabilize the secondary structure elements. The unfolded domain
tends to behave as a four-helix, rather than as a five-helix domain. The ensemble
of residual structures comprises: (i) a set of native structures consisting of
three regions with large helix populations, in rather sharp correspondence with
A, B and E helices, and a small helix population in the second part of the C
helix; (ii) a set of non-native local structures corresponding to turn-like
structures stabilized by several side-chain to side-chain interactions and helix
disruptive side-chains to backbone interactions. Remarkably, residues involved in
these local non-native interactions are also involved, in the native structure,
in structurally important non-local interactions. During the folding process of
annexin I, the local non-native interactions have to switch to native long-range
interactions. This structural switch reveals the existence of a sequence-encoded
regulation of the folding pathways and kinetics, and emphasizes the key role of
the non-native local structures in this regulation.
PMID- 9642093
TI - Exploring the folding pathways of annexin I, a multidomain protein. II. Hierarchy
in domain folding propensities may govern the folding process.
AB - In the context of exploring the relationship between sequence and folding
pathways, the multi-domain proteins of the annexin family constitute very
attractive models. They are constituted of four approximately 70-residue domains,
named D1 to D4, with identical topologies but only limited sequence homology of
approximately 30%. The domains are organized in a pseudochiral circular
arrangement. Here, we report on the folding propensity of the D1 domain of
annexin I obtained from overexpression in Escherichia coli. Unlike the D2 domain,
which is only partially folded, the isolated D1 domain exhibits autonomous
refolding in pure aqueous solution. Similarly, the D3 domain and D2-D3 module
were obtained from expression in E. coli but were found to be largely unfolded.
No conclusion could be drawn for the D4 domain because it was not possible to
extract it from the bacterial inclusion bodies. The data allow us to propose a
plausible scenario for the annexin I folding. This working model states that
firstly the D1 domain folds, and the D2 and D3 domains remain partly unfolded,
facilitating the docking of the D4 domain to the D1 domain. In a second step, the
D1 and D4 domains dock, and D4 may fold if already not folded. The final step
starts with the stabilization of the D1-D4 module. This stabilization is crucial
for allowing the non-native local interactions inside the still partially
unfolded D2 domain to switch to the native long-range interactions involving D4.
This switch allows the complete folding of D2 and D3. The model proposes a
sequential and hierarchical process for the folding of annexin I and emphasizes
the role of both native framework and non-native structures in the process.
PMID- 9642094
TI - Conformational constraints for protein self-cleavage in the proteasome.
AB - The proteasome is the central enzyme of protein degradation in the cytosol and
the nucleus. It is involved in the removal of abnormal, misfolded or incorrectly
assembled proteins, in the processing or degradation of transcriptional
regulators in stress response, in degradation of cyclins in cell-cycle control,
in the destruction of transcription factors or metabolic enzymes in cell
differentiation and metabolic response, and in MHC class I mediated cellular
immune response. By the analysis of the crystal and molecular structures of the
20 S proteasomes from the archaeon Thermoplasma acidophilum and from yeast it was
shown that the beta-type subunits in which the proteolytic activities reside are
members of the N-terminal nucleophile (Ntn) protein family. They are synthesized
as proproteins and become active by autoprocessing at a Gly-1-Thr1 bond. The
Thr1Ala mutant of subunit beta1/Pre3 of the 20 S proteasome from yeast is unable
to autolyse. Its crystal and molecular structure at 2.2 A resolution described
here shows that the pro-segment adopts a well-defined gamma-turn conformation at
Gly-1 and provides a first view at an autolysis site in Ntn hydrolases. The Gly-1
carbonyl oxygen displays two hydrogen bonds. The modelled Thr1 side-chain is
located above the gamma-turn bulge such that addition of its nucleophilic
hydroxyl group to the electrophilic Gly-1 carbonyl carbon atom may proceed by
very small motions. The pro-segment binding site and the catalytic site provide a
rigid structural framework and appropriate hydrogen bond donors for this
reaction. The same structure also supports addition of the Thr1 hydroxyl group to
the carbonyl carbon atom of Leu-2 as a model for the first step in substrate
hydrolysis by the proteasome.
PMID- 9642095
TI - Automated classification of antibody complementarity determining region 3 of the
heavy chain (H3) loops into canonical forms and its application to protein
structure prediction.
AB - A computer-based algorithm was used to cluster the loops forming the
complementarity determining region (CDR) 3 of the heavy chain (H3) into canonical
classes. Previous analyses of the three-dimensional structures of CDR loops (also
known as the hypervariable regions) within antibody immunoglobulin variable
domains have shown that for five of the six CDRs there are only a few main-chain
conformations (known as canonical forms) that show clear relationships between
sequence and structure. However, the larger variation in length and conformation
of loops within H3 has limited the classification of these loops into canonical
forms. The clustering procedure presented here is based on aligning the
Ramachandran-coded main-chain conformation of the residues using a dynamic
algorithm that allows the insertion of gaps to obtain an optimum alignment. A
total of 41 H3 loops out of 62 non-identical loops, extracted from the Brookhaven
Protein Data Bank, have been automatically grouped into 22 clusters. Inspection
of the clusters for consensus sequences or intra-loop interactions or invariant
conformation led to the proposal of 13 canonical forms representing 31 loops.
These canonical forms include a consideration of the geometry of both the take
off region adjacent to the bracing beta-strands and the remaining loop apex.
Subsequently a new set of 15 H3 loops not included in the initial analysis was
considered. The clustering procedure was repeated and nine of these 15 loops
could be assigned to original clusters, including seven to canonical forms. A
sequence profile was generated for each canonical form from the original set of
loops and matched against the sequences of the new H3 loops. For five out of the
seven new H3 loops that were in a canonical form, the correct form was identified
at first rank by this predictive scheme.
PMID- 9642096
TI - Detection of protein three-dimensional side-chain patterns: new examples of
convergent evolution.
AB - Detection of recurring three-dimensional side-chain patterns is a potential means
of inferring protein function. This paper presents a new method for detecting
such patterns and discusses various implications. The method allows detection of
side-chain patterns without any prior knowledge of function, requiring only
protein structure data and associated multiple sequence alignments. A recursive,
depth-first search algorithm finds all possible groups of identical amino acids
common to two protein structures independent of sequence order. The search is
highly constrained by distance constraints, and by ignoring amino acids unlikely
to be involved in protein function. A weighted root-mean-square deviation (RMSD)
between equivalenced groups of amino acids is used as a measure of similarity.
The statistical significance of any RMSD is assigned by reference to a
distribution fitted to simulated data. Searches with the Ser/His/Asp catalytic
triad, a His/His porphyrin binding pattern, and the zinc-finger Cys/Cys/His/His
pattern are performed to test the method on known examples. An all-against-all
comparison of representatives from the structural classification of proteins
(SCOP) is performed, revealing several new examples of evolutionary convergence
to common patterns of side-chains within different tertiary folds and in
different orders along the sequence. These include a di-zinc binding
Asp/Asp/His/His/Ser pattern common to alkaline phosphatase/bacterial
aminopeptidase, and an Asp/Glu/His/His/Asn/Asn pattern common to the active sites
of DNase I and endocellulase E1. Implications for protein evolution, function
prediction and the rational design of functional regulators are discussed.
PMID- 9642097
TI - Frequency of the C282Y mutation of hemochromatosis in five French populations.
AB - Hereditary hemochromatosis mutation 845A (C282Y) in the HFE gene was recently
described, and the C282Y frequencies were reported for various world populations.
The aim of this study was to determine the Y allele frequencies of the C282Y
mutation for five French populations. The most elevated value (= 5.6%) was
obtained for Bretons, in accordance to the hypothesis indicating a Celtic origin
of the hereditary hemochromatosis mutation.
PMID- 9642098
TI - An improved method for generating retroviral producer clones for vectors lacking
a selectable marker gene.
AB - Most retroviral vectors used in preclinical and clinical studies contain a
selectable marker gene to facilitate the generation of producer clones. However,
the expression of such genes in target cells is often undesirable since this may
modify cellular phenotype and invoke a host immune response. Unfortunately, the
efficient identification of high-titer producer clones for vectors lacking a
selectable marker gene continues to be problematic and lacking for a standard
methodology. Despite recent improvements in the screening techniques for
identifying high-titer producer clones without the aid of a selectable marker, a
solution to the fundamental problem of the very low frequency occurrence of high
titer clones within the starting cell population has not emerged. We have
developed a strategy which greatly increases the frequency of virus-producing
clones, including those with high-titer, within the population of transduced
cells to be screened. This approach relies on the use of high-titer vector
preparations generated in 293T cells by co-transfection of retroviral packaging
and vector plasmids. Viral preparations of a vector lacking a selectable marker
were used to repeatedly transduce exponentially growing packaging cells at a high
multiplicity of infection (MOI). Each cell in the resulting polyclonal population
of producer cells contained multiple copies of the unrearranged vector genome.
Greater than 95% of the clones derived from this population produced vector
particles as judged by slot blot analysis of viral RNA from conditioned media.
Numerous clones with estimated titers of 10(5)-10(6) were identified. These
titers were confirmed using a standard vector genome transmission assay. This
approach significantly enhances the ability, without large scale screening, to
easily identify high-titer clones lacking a selectable marker and should
facilitate the routine use of simplified gene marking and therapeutic vectors.
PMID- 9642099
TI - DNA-protein interactions in the proximal zeta-globin promoter: identification of
novel CCACCC- and CCAAT-binding proteins.
AB - The human zeta-globin gene is expressed in a tissue- and developmental-specific
pattern, with expression confined to primitive erythroid cells of the embryonic
yolk sac blood islands. Transgenic mouse studies have shown that the proximal
zeta-globin promoter contains sequences that contribute to the stage-specificity
of expression, but no systematic functional studies of the cis elements in the
proximal zeta-globin promoter have been reported. In this paper, we show that a
number of conserved sequence elements in the zeta-globin promoter are important
for promoter activity in transiently transfected K562 erythroleukemia cells,
which constitutively express zeta-globin. These include a GATA site at -105, a
CCACC site at -93, a CCAAT box at -65, and a TATA box at -29. A highly conserved
CCTCC sequence at -78 is not important for zeta-globin promoter activity in this
system. Mutations at these sites do not result in increased promoter activity in
OCIM1 cells, an erythroid line that does not express zeta-globin, suggesting none
of these sites is a developmental silencer. Electrophoretic mobility shift assays
show that K562 and OCIM1 nuclear extracts contain DNA-binding activities that
interact with the -105 GATA, -65 CCAAT, and -29 TATA sites. In addition K562
cells, but not OCIM1 cells, have an activity that binds the -93 CCACC site. GATA
1 interacts with the GATA site. The K562 CCACC-binding protein is distinct from
Sp1, Sp2, Sp3, Sp4, EKLF, and BKLF. A specific -65 CCAAT-binding activity is
present in K562 and OCIM1 nuclear extracts that is distinct from other CCAAT
binding proteins including CBF/NF-Y, C/EBP, NF-1, and CP2. Thus, we have
identified two novel factors that may contribute to the tissue or developmental
stage-specific expression of zeta-globin.
PMID- 9642100
TI - The human Nramp2 gene: characterization of the gene structure, alternative
splicing, promoter region and polymorphisms.
AB - Nramp2 is a gene encoding a transmembrane protein that is important in metal
transport, in particular iron. Mutations in nramp2 have been shown to be
associated with microcytic anemia in mk/mk mice and defective iron transport in
Belgrade rats. Nramp2 contains a classical iron responsive element in the 3'
untranslated region that confers iron dependent mRNA stabilization. In this
report, we describe a splice variant form of human nramp2 that has the carboxyl
terminal 18 amino acids substituted with 25 novel amino acids and has a new 3'
untranslated region lacking a classical iron-responsive element. This splice form
of nramp2, nramp2 non-IRE, was found to be derived from splicing of an additional
exon into the terminal coding exon. The nramp2 gene is comprised of 17 exons and
spans more than 36 kb. It contains an additional 5' exon and intron (exon and
intron 1) and an additional 3' exon (exon 17) and intron (intron 16) as compared
to nramp1, a homologous gene. The additional exons and introns account for much
of the difference in length between nramp2 (> 36 kb) and nramp1 (12 kb). The exon
intron borders of nramp2 exons 3-15 are homologous to nramp1 exons 2-14. The
nramp2 5' regulatory region contains two CCAAT boxes but lacks a TATA box. The 5'
regulatory region of nramp2 also contains five potential metal response elements
(MRE's) that are similar to the MRE's found in the metallothionein-IIA gene,
three potential SP1 binding sites and a single gamma-interferon regulatory
element. Five single nucleotide mutations or polymorphisms were identified within
the nramp2 gene. One of these, 1303C-->A, occurs in the coding region of nramp2
and results in an amino acid change from leucine to isolecine. A polymorphism,
1254T/C, also occurs in the coding region of nramp2 but does not cause an amino
acid change. The other 3 polymorphisms are within introns (IVS2 + 11A/G, IVS4 +
44C/A, and IVS6 + 538G/Gdel). In addition, a polymorphic microsatellite
TATATCTATATATC (TA)6-7 (CA)10-11 CCCCCTATA (TATC)3 (TCTG)5 TCCG (TCTA)6 was
identified in intron 3. Analysis of cDNA derived by direct amplification of
reversed transcribed RNA or cDNA clones isolated from a library provide evidence
of skipping of exons 10 and 12 of nramp2. Deletion of either of these exons would
result in a sequence that remains in frame yet would generate a protein that
would lack transmembrane spanning region 7 or 8 respectively. The deletion of a
single transmembrane domain would have severe topological consequences. The
coding region of the nramp2 gene of hemochromatosis patients with or without
mutations in the hemochromatosis gene, HFE, were examined and found to be normal.
One hemochromatosis patient, with a normal HFE genotype, was heterozygous for the
1303C-->A mutation. Furthermore, in an examination of hemochromatosis patients
with mutant HFE and normal HFE genes, we did not observe a linkage disequilibrium
of either group with a particular nramp2 haplotype. These data suggest that
mutations in nramp2 are not commonly associated with hemochromatosis.
PMID- 9642102
TI - Calpain: a protease in search of a function?
PMID- 9642103
TI - A second-step splicing activity is conserved from yeast to human.
AB - We describe a defective HeLa nuclear extract which is particularly deficient in
step 2 of splicing reaction. With this extract we have studied the conservation
of a second-step activity from yeast to human cells. We detected a S. cerevisiae
second-step splicing activity that allows restoration of step 2 of the defective
HeLa nuclear extract, which indicates that yeast purified fraction has a second
step activity that is conserved from yeast to human cells. The activity is a
yeast UsnRNP protein(s) since it is purified with anti-trimethylguanosine by
immunoaffinity columns.
PMID- 9642104
TI - Differential regulation of expression of hyaluronan-binding proteoglycans in
developing brain: aggrecan, versican, neurocan, and brevican.
AB - We have used a slot-blot radioimmunoassay to quantitate the levels of hyaluronan
binding chondroitin sulfate proteoglycans in developing rat brain from embryonic
day 14 (E 14) to eight months postnatal. Recombinant nonhomologous regions of the
core proteins were used for immunization to obtain polyclonal antibodies specific
for aggrecan, the alpha and beta domains of versican mRNA splice variants, and N-
and C-terminal portions of neurocan, while brevican was quantitated using a
specific monoclonal antibody. The concentration of aggrecan increased steadily
during brain development up to 5 months of age, when it reached a level that was
18-fold higher than at E14. Alternatively spliced versican isoforms containing
the alpha domain of the glycosaminoglycan attachment region were present at a
relatively low level during the late embryonic and early postnatal period,
decreased by approximately 50% between 1 and 2 weeks postnatal, and then
increased steadily in concentration to reach a maximum at 100 days that was 7
fold that present at 10 days postnatal. In contrast to these results, versican
isoforms containing the beta domain more than doubled in concentration between
E14 and birth, after which they decreased by greater than 90% to reach a low
"mature" level that remained unchanged between 2 and 8 months. The N- and C
terminal portions of neurocan (produced by a developmentally-regulated
proteolytic cleavage in the middle of its chondroitin sulfate attachment region)
both increased in embryonic brain during development, reached a peak in the early
postnatal period, and then declined thereafter. As in the case of aggrecan, only
traces of brevican were detected in embryonic brain and its concentration
increased steadily after birth to reach an adult level that was approximately 14
fold higher than that present in neonatal brain. These striking and distinctive
changes in the concentrations of the different members of this family of
structurally related proteoglycans in developing brain, including changes in
opposite directions for versican mRNA splice variants, indicate that the
individual proteoglycans and their isoforms probably serve unique functions
during nervous tissue histogenesis.
PMID- 9642105
TI - Effect of mRNA cap structure on eIF-4E phosphorylation and cap binding analyses
using Ser209-mutated eIF-4Es.
AB - The in vitro phosphorylation of human recombinant eIF-4E by protein kinase C was
most effective in the absence of m7GTP, supporting a 'performed complex model' as
the mRNA binding step of initiation, i. e., eIF-4E first forms an initiation
complex eIF-4F and is phosphorylated before interacting with mRNA. On the other
hand, the comparison of m7GTP-binding ability of wild-type eIF-4E with those of
four Ser209-mutated ones (S209A, S209D, S209E and S209K) showed that the addition
of anionic charge on Ser209 increases the cap affinity of eIF-4E by repressing
the release of the cap from the complex, not by increasing the complex formation,
suggesting the importance of a retractable ionic bridge between Ser209 and Lys159
in controlling the cap binding by eIF-4E phosphorylation.
PMID- 9642106
TI - Isolation and characterization of LMC, a novel lymphocyte and monocyte
chemoattractant human CC chemokine, with myelosuppressive activity.
AB - By searching the Expressed Sequence Tag (EST) data base, we identified a partial
cDNA sequence encoding a novel human CC chemokine. The entire cDNA sequence was
determined and revealed a CC chemokine whose mature protein consisted of 100
amino acids with predicted molecular weight of 11 kd. The chemokine
preferantially chemoattracted lymphocytes and monocytes but not neutrophils. It
was, therefore, named LMC (Lymphocyte and Monocyte Chemoattractant). LMC
exhibited potent myelosuppressive activity, which was comparable to that of MIP
1alpha. We identified several bacterial artificial clones (BAC) containing the
LMC gene along with two human CC chemokine subfamily members; leukotactin-1 (Lkn
1) and CKbeta8-1/CKbeta8. This data suggests that the LMC gene is located at
human chromosome 17q which encompasses a human CC chemokine gene cluster.
PMID- 9642107
TI - A positively charged alpha-lipoic acid analogue with increased cellular uptake
and more potent immunomodulatory activity.
AB - alpha-Lipoic acid (LA) is taken up by cells and reduced to its potent dithiol
form, dihydrolipoate(DHLA), much of which is rapidly effluxed out from cells. To
improve retention in cells, the LA molecule was modified to confer a positive
charge at physiological pH. N,N-dimethyl,N'-2-amidoethyl-lipoate was synthesized.
The protonated form of the new molecule is referred to as LA-Plus. The uptake of
LA-Plus by human Wurzburg T cells was higher compared to that of LA. Several-fold
higher amounts of DHLA-Plus, the corresponding reduced form of LA-Plus, were
detected in LA-Plus treated cells compared to the amount of DHLA found in cells
treated with LA. At 100 microM, LA did not but LA-Plus inhibited H2O2 induced NF
kappaB activation and NF-kappaB directed IL-2 receptor expression. Both LA and LA
Plus synergised with selenium in inhibiting H2O2 induced NF-kappaB activation. At
150 microM LA-Plus, but not LA, inhibited TNFalpha induced NF-kappaB activation.
At 5 microM LA-Plus, but not LA, protected against both spontaneous and etoposide
induced apoptosis in rat thymocytes. LA-Plus is thus an improved form of LA with
increased therapeutic potential.
PMID- 9642109
TI - Characterization of human mitochondrial RNase P: novel aspects in tRNA
processing.
AB - Human mitochondrial RNase P does not distinguish itself from other RNase P
enzymes by most of its basic properties. 5' phosphates on tRNA products, strict
dependence on a divalent cation, independence of ATP or other cofactors, and
sensitivity to puromycin are generally characteristic for RNase P. Slow
sedimentation of human mitochondrial RNase P in glycerol gradients suggests a
molecular weight considerably lower than that of bacterial or nuclear RNase P. In
contrast to fungi, all putative components of mammalian mitochondrial RNase P are
encoded by the nucleus. Intriguingly, no indication of the involvement of a trans
acting RNA was found in mammalian mitochondrial tRNA processing. Mitochondrial
RNase P is resistant to rigorous treatments with nucleases and exhibits a protein
like density in Cs2SO4 gradients. Moreover, an analysis of copurifying RNAs
revealed no putative RNase P RNA candidates. These data suggest that mammalian
mitochondrial RNase P, unlike its nuclear counterpart or its bacterial relatives,
is not a ribonucleoprotein but a protein enzyme.
PMID- 9642108
TI - Glutathione levels determine apoptosis in macrophages.
AB - Spermine NONOate (SpNO, a nitric oxide donor) induced apoptosis and caspase-3
activity in the macrophage cell line RAW 267.4. RES cells that have been derived
from RAW 267.4 cells by repeated exposure to lipopolysaccharide and interferon
gamma (LPS/INF-gamma), followed by outgrowth of viable cells, are resistant to
apoptosis and caspase-3 activation upon exposure to SpNO. In this study we have
determined that RES cells have lower levels of glutathione (GSH) and a higher
oxidative state than RAW cells. Subsequently, RAW and RES cells were depleted of
GSH by using l-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH
synthesis. GSH depleted cells did not undergo apoptosis nor demonstrate caspase-3
activity when they were exposed to SpNO. These results suggest that the redox
status of the cell is one of the key factors mediating the apoptotic pathway in
which glutathione plays a critical role in mediating apoptosis via NO* and
reactive oxygen species (ROS).
PMID- 9642110
TI - A role of calcineurin in coreceptor regulation during differentiation of Cd4+Cd8+
T cells.
AB - The immunosuppressant FK506 inhibits thymocyte positive selection. Calcineurin, a
FK506-sensitive Ca2+/calmodulin-dependent protein phosphatase, is presumed to be
involved in this event without direct evidence. We have previously shown that
moderate stimulation of CD4(+)CD8(+) thymocytes with a combination of the calcium
ionophore ionomycin and phorbol myristate acetate mimics positive selection
events including downregulation of CD8 expression. Moderate stimulation of a
CD4(+)CD8(+) T cell line with the same combination of drugs also induced specific
downregulation of CD8 expression. FK506 inhibited the CD8 downregulation in both
cell types. The T cell line was transfected with an expression vector encoding an
active form of calcineurin. The transfectans remained CD4(+)CD8(+), but became
CD4(+)CD8(-) or CD4(+)CD8(low) upon stimulation with phorbol myristate acetate
alone. The extent of the CD8 downregulation was correlated with the expression
level of the mutant calcineurin. These results suggest that the calcium signal
for the CD8 downregulation is mainly delivered through calcineurin activation.
PMID- 9642111
TI - Molecular cloning and expression of human cGMP-binding cGMP-specific
phosphodiesterase (PDE5).
AB - A human PDE5 cDNA has been isolated which contains an open reading frame encoding
an 875 amino acid, 100,012 Da polypeptide, the expression of which yields a
protein of the predicted size and is capable of hydrolyzing cGMP. The deduced
amino acid sequence is very similar (95%) to that of bovine PDE5, and comprises a
conserved cGMP-binding domain and catalytic domain. Northern analysis reveals a
major and minor transcript of approximately 9 kb and approximately 8 kb
respectively, thus indicating the existence of at least two splice variants, the
major form being readily detected in bladder, colon, lung, pancreas, placenta,
prostate, small intestine, and stomach.
PMID- 9642112
TI - A novel relative of the very-long-chain acyl-CoA synthetase and fatty acid
transporter protein genes with a distinct expression pattern.
AB - Based on its relationship to very-long-chain acyl-CoA synthetase (VLACS), we have
cloned and identified a novel, VLACS-related (VLACSR) cDNA from mouse liver. The
2067-bp open reading frame encodes a 689-amino-acid protein with a predicted
molecular mass of 76.2 kDa. The carboxy-terminal 500 amino acids of VLACSR show
48% identity and 70% similarity to mouse VLACS and 43% identity and 60%
similarity to mouse fatty acid transporter (FATP), respectively. In addition, a
partial cDNA of the human VLACSR ortholog was identified. By Northern blot
analysis, a 2.6-kb VLACS mRNA was highly abundant only in mouse liver. Low levels
of shorter mRNAs were present in brain, lung, testes, and spleen (2.5 kb) and in
skeletal muscle (2.2 kb). In heart, but not in kidney, transcripts undetectable
by Northern blot analysis could be demonstrated by RT PCR. Southern blot analysis
indicated single-copy VLACSR genes in the mouse and human genomes.
PMID- 9642113
TI - Rapid enhancement of high affinity glutamate uptake by glucocorticoids in rat
cerebral cortex synaptosomes and human neuroblastoma clone SK-N-SH: possible
involvement of G-protein.
AB - The rapid effects of glucocorticoids(GCs) on the Na+dependent, high affinity
uptake of 3[H]-L-glutamate(Glu) in rat cerebral cortex synaptosomes(4 min
incubation) and human neuroblastoma clone SK-N-SH (10min preincubation and 5 min
incubation) were investigated. GCs, including corticosterone, corticosterone
sulfate, hydrocortisone-hemisuccinate and dexamethasone 21-phosphate(DEX) were
found stimulating Glu uptake. The uptakes in synaptosomes and SK-N-SH cells were
increased to 117-126% and 121-137% respectively of the control by 10(-6)mol/L
GCs. The stimulation of GCs was dose-dependent. The maximal effect of DEX in SK-N
SH cells appeared at10(-7)mol/L, and the least effective dose of DEX was at 10(
9)mol/L. Guanosine 5-O-(2-thiodiphosphate), an inhibitor of G-protein activation,
could block the stimulation of GCs. The results indicated that GCs rapidly
enhance the Na+-dependent high affinity Glu uptake in nerve endings and SK-N-SH
cells, even at the concentration of physiological conditions, and the G-protein
on synaptic membranes or SK-N-SH cell membranes might be involved in the effect
of GCs.
PMID- 9642114
TI - Identification and cloning of an orphan G protein-coupled receptor of the
glycoprotein hormone receptor subfamily.
AB - Mining of the EST database identified a human EST that was predicted to encode a
novel member of the glycoprotein hormone receptor subfamily. Based on the
sequence information, the full-length coding region of this gene was isolated and
sequenced. This gene, designated HG38, is predicted to encode a polypeptide of
907 amino acid residues with a putative signal peptide sequence at its very N
terminus. HG38 is most closely related to members of the glycoprotein hormone
receptor subfamily with approximately 35% overall identity at the protein
sequence level. As with the glycoprotein hormone receptors, HG38 contains a long
extracellular domain with a total of 16 leucine-rich repeats. Northern blot
analysis showed that HG38 was expressed in skeletal muscle, placenta, spinal
cord, and various regions of the brain. Radiation hybrid mapping placed HG38 into
human chromosome 12q22-23. HG38 is most likely to be a receptor for a novel class
of glycoprotein ligands.
PMID- 9642115
TI - Phagocyte NADPH oxidase p67-phox possesses a novel carboxylterminal binding site
for the GTPases Rac2 and Cdc42.
AB - Rac GTPases regulate activation of the phagocyte NADPH oxidase, a multi-component
enzyme complex that produces superoxide in response to host infection. GTP-bound
Rac binds to the cytosol protein p67-phox enabling it to participate in oxidase
assembly. Details of this interaction are poorly understood. Previous studies
showed that Rac/p67-phox binding is GTP-dependent and that several Rac1 mutants
lost the ability to activate the oxidase even though they still bound p67-phox.
Using two hybrid and blot overlay binding methods, we identified a novel binding
site in the p67-phox C-terminus that binds Rac1, Rac2, and Cdc42, a related
GTPase which does not activate the oxidase. Binding was independent of the
GDP/GTP state. We also showed that GTP-Cdc42 binds p67-phox N-terminus similar to
GTP-Rac. Therefore, Rac binding to p67-phox is not synonymous with NADPH oxidase
activation, and Rac probably participates in other steps of oxidase activation in
addition to binding p67-phox.
PMID- 9642116
TI - Male-associated hypertension in LDL-R deficient mice.
AB - Hypertension is more common among African Americans than Americans of European
descent. However, the genetic etiology has not been defined. Similarly,
lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is
higher among African Americans. To explore the relationship between Lp (a) and
hypertension, we measured the blood pressure of transgenic mice expressing
apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we
also determined blood pressure for apoE deficient mice, low density lipoprotein
receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression
was not associated with hypertension. Surprisingly, LDL-R deficient mice
exhibited male-associated hypertension. This observation could explain the higher
incidence of atherosclerosis in male LDL-R deficient mice and human familial
hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to
photochemically induced cerebral stroke. However, this hypersensitivity was only
modestly associated with sexual dimorphism. The presented data suggest that LDL-R
deficiency results in hitherto unrecognized changes in the vascular tone.
PMID- 9642117
TI - Characterization of a novel liver-specific protein/DNA binding site in the human
HMG CoA reductase promoter.
AB - These studies define a novel binding element (site C) within the human HMG CoA
reductase promoter using a combination of in vitro DNase I footprinting and gel
mobility shift assays. The factor interacting with site C appears to be
restricted to the liver, indicating a possible role for this protein in
regulating hepatic expression of the gene. Studies based on competitive gel
mobility shift assays and transient co-transfection experiments performed using a
reporter construct harbouring the promoter of HMG CoA reductase suggest that the
protein binding to site C may belong to the C/EBP family of transcription
factors. A factor interacting with this binding element was also identified in
human liver nuclear protein extracts.
PMID- 9642118
TI - Tissue restricted expression of two human Frzbs in preadipocytes and pancreas.
AB - Frzb is a newly discovered family of secreted glycoproteins that function to
modulate signaling activity of Wnt. Frzb proteins share sequence homology with
the extracellular domain of the Wnt receptor (frizzled) and are capable of
binding to Wnt. Thus, Frzb functions to antagonize Wnt activity by sequestering
Wnt and preventing its binding to the frizzled receptor. Since the initial
identification of bovine and human Frzb, several related members of this family
have been isolated from rodent and human. In this paper, we describe the cloning
and expression of two human frzb homologues termed hFRP-1b and hFRP-2. These
human FRPs share significant homology to mouse sFRP-1 and sFRP-2 (55 and 98%
identity at amino acid level, respectively). Northern blot experiments revealed
that these Frzb homologues have highly restricted tissue distribution. hFRP-1b is
exclusively expressed in pancreatic tissue while high levels of hFRP-2 were found
in adipose tissue. In addition, low levels of hFRP-2 were also observed in other
tissues including heart, pancreas and muscle. Remarkably, FRP-2 is predominantly
expressed in un-differentiated preadipocytes in both rodent and man. The
expression of FRP-2 is also significantly reduced in fat pads from obese mice.
Taken together, these data indicate that distinctive members of the Frzb family
exhibit different expression patterns in vivo, suggesting their ability to
modulate diverse aspects of Wnt signaling. The expression and dysregulation of
sFRP-2 in fat and obesity also suggest a potential roles on the Wnt signaling
pathway in the pathology of obesity and related metabolic diseases. Molecular
cloning and expression of these Frzbs will allow detailed molecular and
biochemical analysis of Wnt-Frzb interaction and their impact on Wnt-Frizzled
receptor signal transduction.
PMID- 9642119
TI - Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are
mediated via impairment of receptor tyrosine kinase signaling and perturbation in
cell cycle progression.
AB - Enhanced tyrosine kinase activity due to aberrant or overexpression of receptor
and/or non-receptor tyrosine kinases has been implicated in a variety of human
malignancies including cutaneous neoplasms. Epidermal growth factor receptor
(EGFR)-mediated tyrosine phosphorylation may be a primary indicator of signal
transduction regulating cell growth and proliferation. Recent studies have shown
that skin tumor promoters such as phorbol ester and ultraviolet B radiation
activate EGFR in mouse skin as well as in cell culture. Similarly, oxidative
stress, which is implicated in skin tumor promotion, also activates EGFR-mediated
cell signaling. Since this signaling pathway has been suggested to be involved in
skin tumor promotion, its impairment by antioxidants may lead to an efficient way
for skin cancer prevention and therapy. Recently, we showed that silymarin, a
flavonoid antioxidant, affords exceptionally high to complete protection against
several skin tumor promoters caused tumor promotion in mouse skin. Employing
human epidermoid carcinoma cells A431 that contain overexpressed EGFR, in this
study, we assessed whether the anti-skin tumor promoting effects of silymarin are
due to its inhibitory effect on EGFR activation and down stream signaling pathway
leading to perturbations in cell cycle progression. Treatment of cells with
silymarin resulted in a significant inhibition of ligand-induced activation of
EGFR with no change in its protein levels. Silymarin treatment also resulted in a
significant decrease in tyrosine phosphorylation of Shc, an immediate downstream
target of EGFR, but no change in the protein levels of Shc. The inhibition of
EGFR activation by silymarin was associated with a highly significant to complete
inhibition of EGFR intrinsic kinase activity. Cells treated with silymarin also
showed a significant G2-M arrest in cell cycle progression, and a highly
significant inhibition of DNA synthesis and cell growth in a dose-dependent
manner. Taken together, these results suggest that skin cancer chemopreventive
effects of silymarin are mediated via impairment of EGFR signaling which
ultimately leads to perturbation in cell cycle progression resulting in the
inhibition of proliferation and induction of growth arrest.
PMID- 9642120
TI - Identification and characterization of a new human gene encoding a small protein
with high homology to the proline-rich region of the SH3BGR gene.
AB - As part of an effort to identify genes potentially involved in the Down Syndrome
pathogenesis, in this paper we report the identification and characterization of
a new human gene (named SH3BGRL), which shows a high homology to the SH3BGR gene,
previously mapped to the Down Syndrome region of chromosome 21. The SH3BGRL gene
encodes for a small protein of 114 amino acids, sharing 60% identity and 84%
conservation on the amino acid level with the middle, proline-rich region of the
SH3BGR gene and containing a similar SH3 (Scr homology 3) binding motif. The
SH3BGRL and the proline-rich region of SH3BGR proteins appear to be highly
conserved, sharing 95 and 98% identity, respectively, with the mouse homologues.
A 1.9 kb transcript of the SH3BGRL gene has been found in all the tissues
examined, in contrast with the expression pattern of the SH3BGR gene which is
transcribed only in heart and skeletal muscle. The SH3BGR gene and its homologue,
SH3BGRL, could be members of a new family of genes containing a highly conserved
proline-rich functional domain. The SH3BGRL gene has been mapped by fluorescent
in situ hybridization to Chromosome Xq13.3.
PMID- 9642121
TI - Differential expression of alpha3 fucosyltransferases in Th1 and Th2 cells
correlates with their ability to bind P-selectin.
AB - One of the key control points in the trafficking of the T cell effector subsets,
Th1 and Th2, to sites of inflammation is their migration out of the bloodstream.
The mechanism by which the cells initially adhere to the endothelium is dependent
on the selectin family of adhesion molecules. Only polarised Th1 cells are
capable of binding P-selectin despite both Th1 and Th2 cells expressing PSGL-1,
the P-selectin ligand. This may be due to a secondary modification of PSGL-1 that
is present on Th1 but not Th2 cells. One key modification of PSGL-1 is the alpha3
fucosylation of the O-glycans. To address whether the binding of Th1 and Th2
cells may be regulated by fucosylation, we have studied the expression of the
alpha3 fucosyltransferases, FucT-IV and VII, using in vitro differentiated mouse
T cells. Messenger RNA levels for both FucT-IV and VII were found to be higher in
Th1 than Th2 cells. alpha3 fucosyltransferase enzyme activities were also
elevated in Th1 cells. The increased expression of the alpha3 fucosyltransferases
in Th1 cells correlated with the ability of Th1, but not Th2, cells to bind to P
selectin. Thus, the regulation of the binding of effector T cells to the
endothelium, and subsequent trafficking to inflammatory sites, may be controlled
by the fucosylation state of PSGL-1 mediated by the selective expression of the
alpha3 fucosyltransferases.
PMID- 9642122
TI - Detection of endogenous biotin-containing proteins in bone and cartilage cells
with streptavidin systems.
AB - When utilizing streptavidin systems with Western blots of chondrocyte, osteoblast
and osteoclast lysates, proteins of the molecular weights 116 kDa, 75 kDa and 67
kDa were observed to be bound by streptavidin alone. Streptavidin binding could
not be blocked by pre-incubation with an RGD containing peptide. The same
proteins were bound by ExtrAvidin which lacks the RGD sequence present in
streptavidin. Pre-incubation with free biotin completely abolished the binding of
both streptavidin and ExtrAvidin. The three proteins observed are believed to be
the biotin containing carboxylases: pyruvate carboxylase, 3-methylcrotonyl
carboxylase, and propionyl carboxylase. The findings of this study underscore the
need to apply vigorous controls to distinguish between endogenous biotinylated
proteins and biotin used as a means to amplify avidin detection systems since a
wide variety of proteins with relevance to bone and cartilage biology have
molecular weights similar to the biotin carboxylases.
PMID- 9642123
TI - Epitope-specific focusing of the immune response to a minimized human chorionic
gonadotropin analog.
AB - Minimized proteins have long been used to elicit an immune response to particular
regions of a protein antigen. Most efforts to derive minimized proteins have
employed synthetic peptide fragments. This approach works well for linear
epitopes but poorly for conformational epitopes. Here we describe a homodimeric
human chorionic gonadotropin (hCG) analog that retains the conformation of
related parts of hCG and elicits high affinity specific antibodies. This novel
immunogen displays the tertiary structure of selected loops of the protein but
lacks structures that could elicit potentially undesirable antibodies.
PMID- 9642124
TI - Differential expression of alternatively spliced c-erbB-2 mRNA in primary tumors,
lymph node metastases, and bone marrow micrometastases from breast cancer
patients.
AB - We established an RT-PCR method to measure the amount of a 2.3-kb alternatively
spliced mRNA of the human c-erbB-2/HER-2 proto-oncogene relative to the 4.6-kb
full-length transcript. For the first time, we demonstrated production of c-erbB
2 extracellular domains via alternative splicing in breast cancer tissues, lymph
node and bone marrow micrometastases. In 15 c-erbB-2-positive primary breast
tumor samples, we found two significantly distinct subgroups: 6/15 had a low
level of the extracellular fragment, and 9/15 showed an average 4.4-fold higher
amount of the alternatively spliced mRNA. Additionally, six lymph nodes and six
bone marrow aspirates from metastatic breast cancer patients were analyzed: 5/6
lymph nodes and 6/6 bone marrow aspirates were found to produce elevated relative
amounts of the truncated fragment. The results demonstrate that our method is
suitable for sensitive detection of c-erbB-2-positive micrometastasis and
strongly suggest that the alternatively spliced c-erbB-2 variant is involved in
the development of micrometastasis in breast cancer.
PMID- 9642126
TI - A functional eukaryotic promoter is contained within the first intron of the hGH
N coding region.
AB - Human growth hormone is frequently used as a reporter gene in studies addressing
the regulation of eukaryotic promoters. Here we present evidence that the first
intron of the hGH-N coding region contains a novel eukaryotic promoter which is
able to direct the expression of hGH-N and luciferase reporter genes. The
corresponding transcriptional initiation site is located downstream of the splice
acceptor site of exon 2. This internal hGH-N promoter can interfere with the
transcriptional control elements of a promoter linked to the hGH-N coding region
and thereby complicate the interpretation of data obtained with hGH-N as a
reporter gene.
PMID- 9642125
TI - A matrix metalloproteinase proenzyme activator produced by articular cartilage.
AB - Matrix metalloproteinases (MMPs) are involved in connective tissue turnover under
physiological and pathological conditions. MMP activity is regulated by the
requirement for zymogen activation. This report describes a proMMP-3 activator
produced by articular cartilage. The activator initiates a step-wise processing
of proMMP-3 to generate an array of active species. Sequencing of activation
intermediates demonstrated cleavage on the NH2-terminal side of certain basic
residues in the MMP-3 propeptide. Metal ion chelators inhibited activator
dependent proteolysis, and activity was restored by low levels of ZnCl2. These
catalytic properties suggest similarity to members of the insulinase superfamily
of metalloendopeptidases with in vitro specificity for single arginine or paired
basic processing sites in a variety of prohormones. Dibasic sites also exist in
the propeptides of several MMPs including proMMP-3. This is the first report that
cartilage produces a potent MMP proenzyme activator, opening the possibility of a
novel intrinsic activation pathway for catabolic processes in this avascular
tissue.
PMID- 9642127
TI - Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone
marrow stroma cells.
AB - The recently cloned osteoclastogenesis inhibitory factor, or osteoprotegerin
(OPG), has been shown to be a potent inhibitor of osteoclast formation. The
inhibition is believed to be mediated through specific binding of OPG to a cell
surface ligand on osteoblastic stromal cells. In this report we have studied the
effect of the bone resorbing agent prostaglandin E2 (PGE2) on OPG mRNA levels in
primary cultures of human bone marrow stroma cells (hBMSC). PGE2 dose- and time
dependently down-regulated the mRNA levels of OPG, as measured by RNAse
protection assay. After 4 hours of stimulation with 1 microM PGE2, OPG mRNA
levels were significantly decreased. The inhibitory effect was seen at and above
1 nM of PGE2. To elucidate whether the OPG mRNA levels are regulated via the
proteinkinase A and/or the proteinkinase C pathways we stimulated cells with
either forskolin (FSK) or phorbolic ester (PDbu) respectively. FSK (10 microM)
decreased OPG mRNA levels to 50 % of control, whereas PE (10 nM) upregulated the
mRNA levels to 250 % of control. These data show that PGE2 down-regulates the
expression of OPG mRNA in hBMSC, probably via an increase in cAMP. This mechanism
might be involved in PGE2-induced bone resorption.
PMID- 9642128
TI - Suppression of type I collagenase expression by antisense RNA in melanoma cells
results in reduced synthesis of the urokinase-type plasminogen activator
receptor.
AB - Previously we reported that suppression of type I collagenase synthesis in human
melanoma cells with antisense RNA significantly reduced proteolysis of type I and
type IV collagen matrices (Durko et al., 1997, Biochim. Biophys. Acta 1356, 271).
Because plasmin is a major activator of the type I collagenase, we assessed the
impact of type I collagenase suppression on the urokinase/plasmin system of
proteolysis. Gel zymography revealed the appearance of two new caseinolytic bands
of Mr 81-83000 in conditioned media of type I collagenase-depleted, but not of
wild-type cells and these were identified as plasmin bands. This increased
extracellular plasmin activity coincided with reduced membrane-associated
plasminogen levels and decreased expression of the urokinase-type plasminogen
activator receptor at both the mRNA (up to 83% reduction) and cell-surface (up to
48% reduction) levels, while urokinase mRNA levels remained unchanged. The
results indicate that in these cells the urokinase/plasmin system is regulated by
type I collagenase levels.
PMID- 9642129
TI - The potential of various HIV-1 mutants to inhibit the replication of wild-type
virus.
AB - We have previously demonstrated that many of gag mutants of human
immunodeficiency virus type 1 (HIV-1) inhibited the replication of wild-type (wt)
HIV-1. In this study, various HIV-1 mutants were systematically analyzed with
respect to their ability to suppress the replication of wt HIV-1. Sixteen mutants
of all eight HIV-1 genes other than gag were evaluated for their inhibitory
effects. Only an env mutant designated NL-Hi efficiently interfered with the
replication of wt HIV-1 in a single round of infection. The NL-Hi did not affect
the late replication processes of wt virus, including transcription, translation,
and assembly/release. Virions produced in the presence of the mutant Env were
defective for the viral entry process in the early phase of HIV-1 replication
cycle.
PMID- 9642130
TI - Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in rat
aortic smooth muscle cells.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of nuclear
receptors, is expressed at a high level in adipose tissue and plays an important
role in adipocyte differentiation. In the present study, we identified the
expression of PPARgamma in rat aortic smooth muscle cells (RASMC) using reverse
transcription-polymerase chain reaction and gel mobility shift assay. In
addition, to investigate whether PPARgamma in RASMC is functional or not, we
examined the effect of two specific ligands for PPARgamma, a thiazolidinedione
anti-diabetic agent, troglitazone, and 15-deoxy-Delta12,14-prostaglandin J2, on
the transcriptional activity of PPAR responsive element (PPRE). A significant
increase in the activity of PPRE by addition of these ligands was found. These
results suggest that in RASMC, target genes for PPARgamma may be activated by
specific ligands for PPARgamma through PPRE in their promoters. In conclusion,
PPARgamma is expressed and functional in vascular smooth muscle cells.
PMID- 9642131
TI - Expression of the BCL6 gene in the pre- and postnatal mouse.
AB - Human BCL6, also called LAZ3, is a protein involved in gene regulation and
abnormal expression of BCL6 and has been implicated in the tumorigenesis of non
Hodgkin lymphoma. We have analyzed the expression of murin bcl6 in pre- and
postnatal mouse using in situ hybridization histochemistry and Northern blotting.
The developing olfactory epithelium in the nasal cavity was the only tissue
displaying a positive bcl6 mRNA signal in the day 14 embryo. At gestational day
17, expression was primarily seen in skeletal muscle, olfactory epithelium, and
thymus, and also in the epithelium lining the upper airways and esophagus. In
selected tissues from postnatal mouse, bcl6 expression was detected in brain,
renal cortex, spleen, and thymus. The expression in brain was restricted to the
pyramidal cell layer of the cerebral cortex and the hippocampus regions CA1 and
CA2, and the dentate gyrus. Our results show that bcl6 expression is not confined
only to organs of the lymphatic system, such as spleen and thymus. Thus, bcl6 may
be active as a regulator of gene transcription in many different cell types,
including epithelial and nerve cells.
PMID- 9642132
TI - Effects of oxygen on vascular patterning in Tie1/LacZ metanephric kidneys in
vitro.
AB - Tie1 is an endothelial lineage-specific receptor. Using Tie1/LacZ mice we
previously demonstrated in situ differentiation of glomerular capillaries after
transplantation of renal precursors into the neonatal nephrogenic kidney cortex.
We now report studies with Tie1/LacZ metanephric kidneys explanted in vitro at a
stage when Tie1/LacZ-expressing cells surround nephron precursors but glomeruli
are unformed. After 4 days of serum-free organ culture in 21% O2, transgene
expressing vessels regressed. In contrast, in 3% O2, transgene was expressed
between epithelial tubules by cellular masses containing poorly defined lumens.
The normal branching of Tie1/LacZ-expressing vessels which occurred in vivo was
absent in vitro and glomeruli forming in culture lacked capillaries. Similar
observations were made in wild-type metanephroi using vascular endothelial growth
factor receptor 2 (Flk1) as an endothelial marker. We speculate that the
metanephros is hypoxic in vivo to permit endothelial growth but other cues must
be required for construction of the microcirculation since hypoxia failed to
elicit normal patterning in vitro.
PMID- 9642133
TI - Primary structure and molecular modeling of mistletoe lectin I from Viscum album.
AB - The first three-dimensional structure of the ribosome inactivating protein
mistletoe lectin I (ML-I) from Viscum album has been modeled on the basis of the
X-ray structure of castor bean ricin from Ricinus communis. The relative high
sequence homology and conserved secondary structure enabled accurate modeling.
The 196 sequence changes between ML-I and ricin could be accomodated with only
little pertubation in the main chain folding. A close comparison of the primary
structures of ML-I and ricin is given and the effects of the sequence changes are
elucidated on the basis of the modeled three-dimensional structure. Differences
have been identified in the vicinity of the active site, in the high affinity
galactose binding site and in the interface between the A and B chains, which
might account for the reduced cytotoxicity of ML-I.
PMID- 9642134
TI - TNFalpha disrupts mitotic clonal expansion and regulation of retinoblastoma
proteins p130 and p107 during 3T3-L1 adipocyte differentiation.
AB - The inhibitory effects of TNFalpha on adipocyte differentiation are well
described, however, the mechanisms are poorly understood. Early during hormonally
induced 3T3-L1 preadipocyte differentiation there is a requisite mitotic clonal
expansion phase that is associated with significant regulation in p130 and p107
protein levels, two members of the retinoblastoma protein family that regulate
cell cycle events through interactions with the E2F transcription factors. This
regulation occurs within the first 24 hours of differentiation (Day 1) and is
characterized by a transient increase in p107 protein and mRNA levels as well as
a transient decrease in p130 protein levels. Here we describe that TNFalpha
disrupts the normal pattern of expression of both p130 and p107 proteins, leading
to a complete block in mitotic clonal expansion. Interestingly, TNFalpha-treated
cells enter S-phase as determined by 5-bromo-2'-deoxyuridine uptake experiments,
but rather than completing cell cycle, they are stimulated to undergo apoptosis.
PMID- 9642135
TI - p202 prevents apoptosis in murine AKR-2B fibroblasts.
AB - p202 is an interferon (IFN)-inducible, primarily nuclear, phosphoprotein (52-kDa)
whose overexpression in transfected cells inhibits colony formation. p202 binds
to the retinoblastoma tumor suppressor protein and two other members of the
pocket family proteins (p107 and p130). Moreover, overexpression of p202 in
transfected cells inhibits the transcriptional activity of E2Fs (E2F-1/DP-1 and
E2F-4/DP-1), p53, AP-1 c-Fos and c-Jun, NF-kappaB p50 and p65. Here we
demonstrate that inhibition of endogenous p202 production in murine AKR-2B
fibroblasts did not result in an increase in cell proliferation. Instead, these
cells exhibited increased susceptibility to apoptosis in response to decrease in
serum concentrations in the growth medium. These observations are consistent with
the notion that normal levels of p202 may be needed for the regulation of cell
proliferation.
PMID- 9642136
TI - Silencing of CYP1A1 expression in rabbits by DNA methylation.
AB - Unlike most experimental animals, treatment of adult rabbits with 3
methylcholanthrene (MC) does not induce the expression of the CYP1A1 gene. In
this study, we show that DNA methylation plays one of the key roles in the
suppression of CYP1A1 gene expression. S1 nuclease protection assay showed that
the induction of CYP1A1 mRNA by MC occurred in rabbit kidney RK13 cells but not
in rabbit lung R9ab cells, while aryl hydrocarbon receptor (AhR) and AhR nuclear
translocator (Arnt) mRNAs were expressed in both cells at similar levels.
Interestingly, the treatment of R9ab cells with a DNA demethylating agent, 5-aza
2'-deoxycitidine, resulted in the induction of the expression of the CYP1A1 gene
by MC. The results indicate that DNA methylation is one of the factors involved
in the loss of the MC-induced expression of the CYP1A1 gene. Thus, it seemed that
the binding of the AhR/Arnt complex to the xenobiotic-responsive element (XRE)
was inhibited by the hypermethylation of CpG dinucleotides within an XRE core
sequence (5'-CGTG-3'). To explore this possibility, we compared the methylation
status of XRE in R9ab cells with that in RK13 cells. A bisulfite sequence
analysis using genomic DNAs from R9ab cells showed that the CpG site within XRE
was highly methylated on both coding and non-coding strands. In contrast to this
result, the hypomethylation of XRE was seen in RK13 cells. To examine whether or
not the binding of the AhR/Arnt heterodimer to XRE is affected by the methylation
status of XRE, a gel shift assay using a methylated XRE as a probe was carried
out. As expected, the AhR/Arnt complex could not bind to the methylated XRE. From
these results, we conclude that the cell type-specific transcription of the
rabbit CYP1A1 gene is caused by DNA methylation.
PMID- 9642137
TI - Different effect of diastereoisomers of L-cystathionine sulfoxide on the stimulus
coupled responses of human neutrophils.
AB - The priming effect of L-cystathionine sulfoxide, which is one of the unusual
cystathionine metabolites found in the urine of patients with cystathioninuria,
on the stimulus-induced superoxide generation by human neutrophils was examined.
The synthetic L-cystathionine sulfoxide significantly enhanced the superoxide
generations induced by N-formyl-methionyl-leucyl-phenylalanine [fMLP], opsonized
zymosan [OZ], arachidonic acid [AA], and phorbol 12-myristate 13-acetate [PMA].
Then the synthetic L-cystathionine sulfoxide was separated into two
diastereoisomers, CS-I and CS-II, which showed a peak at 76 and 83 min on
chromatogram by amino acid analyzer, respectively. CS-I enhanced the superoxide
generations induced by AA and PMA but not those induced by fMLP and OZ. On the
contrary, CS-II enhanced the superoxide generations induced by fMLP and OZ but
not those induced by AA and PMA. The superoxide generation induced by PMA with CS
I was suppressed by H-7 and was enhanced by genistein, while that by fMLP with CS
II was suppressed by genistein and was enhanced by H-7.
PMID- 9642138
TI - Transcriptional activity of RBCK1 protein (RBCC protein interacting with PKC 1):
requirement of RING-finger and B-Box motifs and regulation by protein kinases.
AB - The RBCK1 protein was recently identified as a protein kinase C-interacting
protein with a new type of RBCC (RING-B-Box-Coiled-coil) region, possessing both
DNA-binding and transcriptional activities unlike other proteins in the RBCC
protein family (Tokunaga et al. Biochem. Biophys. Res. Commun. 244, 353-359,
1998). To identify protein motifs in the RBCC region of RBCK1 essential for the
transcriptional activity, RBCK1 mutant proteins have been constructed and
analyzed by using the GAL4 chimeric transcription regulator system. We have found
that both of the RING-finger and the B-Box motifs are indispensable for the
transcriptional activity of RBCK1. This is the first observation that these
protein motifs of the RBCC protein family play a crucial role in transcriptional
activation. In addition, we have examined the effect of co-expression of several
protein kinases on the transcriptional activity of RBCK1. Protein kinase A (PKA)
was found to enhance the activity by about eightfold, whereas both ERK
(extracellular signal-regulated kinase) activator kinase 1 (MEK1) and MEK kinase
1 (MEKK1) significantly repressed the activity. Because RBCC proteins are
presumed to act as a proto-oncoprotein, these results suggest that the RBCK1
protein is involved in the intracellular signaling cascades along with PKA, MEK1,
and MEKK1 and mediates cell growth and differentiation.
PMID- 9642139
TI - Artificial imitation of glutathione peroxidase with 6-selenium-bridged beta
cyclodextrin.
AB - On the basis of cyclodextrin, 6-selenium bridged beta-cyclodextrin (6-beta-CD-Se
Se-beta-CD, known as 6-SeCD) was synthesized by the selective tosylation of beta
cyclodextrin and nucleophilic displacement by sodium hydroselenide to imitate
glutathione peroxidase (GPX). The GPX activity of diselenide 6-SeCD is 4.3 times
that of PZ51. The structure of the mimic 6-SeCD was characterized by means of
laser mass spectroscopy, elemental analysis, IR and 1H NMR. The selenium content
and its valence in 6-SeCD were determined by means of X-ray photoelectron
spectra. Kinetics of the mimic showed that its enzymatic behavior was similar to
that of native GPX.
PMID- 9642140
TI - Rapid fragmentation of vimentin in human skin fibroblasts exposed to tamoxifen: a
possible involvement of caspase-3.
AB - Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of
breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are
obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM)
in human skin fibroblasts, in a time and dose dependent manner. Addition of
caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM,
and caspase-3 was proteolytically activated by TAM treatment. Expression of
functional estrogen receptors were negative in these cells, and neither
transcription nor protein synthesis was required for TAM-induced degradation of
VIM. Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded VIM,
whereas neither estradiols nor estriol had any effects. Taken together, TAM may
induce fragmentation of VIM associated with an activation of caspase-3, which may
be attributed to non-genomic actions of TAM.
PMID- 9642141
TI - Retinoic acid induction of calcium channel expression in human NT2N neurons.
AB - Ca2+ channel expression and regulation of intracellular Ca2+ homeostasis were
studied during retinoic acid (RA)-induced differentiation of the human
teratocarcinoma cell line Ntera 2/C1.D1 (NT2- cells) into NT2N neurons, a unique
model of human neurons in culture. The cytosolic Ca2+ level of undifferentiated
NT2- cells was low (75 +/- 5 nM) and stable under basal conditions, and it was
only marginally decreased (by 9%) upon removal of extracellular Ca2+. After 10
microM RA treatment, NT2- cells were irreversibly differentiated into a phenotype
of neuron-like NT2N cells. Cytosolic Ca2+ level of NT2N neurons was higher (106
+/- 14 nM) than that of NT2- cells and spontaneously fluctuated (0.208 +/- 0.038
transients/min) under basal conditions. Although K+ increased 86Rb fluxes in both
NT2- cells and NT2N neurons, it only increased cytosolic Ca2+ level in NT2N
neurons. The K+-induced increase in cytosolic Ca2+ in NT2N neurons was
antagonized by 0.1-10 microM nifedipine or verapamil, 5 microM omega-CgTx GVIA,
but not by 1 microM omega-agatoxin IVA, 1 microM omega-agatoxin TK, 1 microM FTX
3.3, or 100 microM Ni+ implicating L- and N-type voltage-dependent Ca2+ channels.
In L- and N-type channels, but not in P- and Q-types, mRNAs were expressed in
NT2N neurons as well as NT2- cells. Quantitative analysis of L- and N-type Ca2+
protein levels showed major differences between NT2- cells and NT2N neurons. In
NT2- cells, N-type Ca2+ channels were undetectable while L-type channels levels
were fivefold lower compared to NT2N neurons. Our findings show that L- and N
type channels are expressed during differentiation of NT2- cells into neurons,
and that these voltage-dependent Ca2+ channels have a major role in regulating
intracellular Ca2+ homeostasis and neuronal excitability.
PMID- 9642142
TI - Selective inhibition by kringle 5 of human plasminogen on endothelial cell
migration, an important process in angiogenesis.
AB - Angiogenesis is a multi-step process that includes endothelial cell
proliferation, migration, basement membrane degradation, and new lumen
organization. Angiostatin, an internal fragment of plasminogen comprising the
first four triple disulfide-linked kringle structures, is one of the most potent
endogenous angiogenesis inhibitors described to date. The kringle 5 domain of
plasminogen, which shares high sequence homology with the four kringles of
angiostatin, was previously shown to antagonize endothelial cell growth. We now
describe that the recombinant kringle 5 of human plasminogen inhibits endothelial
cell migration with an IC50 (concentration for half maximal inhibition) of
approximately 500 nM. We demonstrate that the lysine-binding sites of kringle 5
may not be involved in its anti-migratory activities. The anti-migratory activity
of kringle 5 is similar to that of angiostatin. Kringle 5 also shows selective
inhibition on endothelial cells as opposed to other cell types. Relative to its
native form, reduced kringle 5 displays a significant increase in anti-migratory
activity, implying that the kringle conformation may shield kringle 5 from
effectively interacting with endothelial cells. This report thus constitutes the
first demonstration that kringle 5 of plasminogen is a selective inhibitor for
endothelial cell migration.
PMID- 9642143
TI - A critical role for tyrosine residues in His6Ni-mediated protein cross-linking.
AB - A new type of affinity cross-linking strategy has been developed in which His6
tagged proteins can be cross-linked to their binding partners in the presence of
unmodified proteins (D. Fancy, K. Melcher, S. A. Johnston, and T. Kodadek, 1996,
Chem. Biol. 3, 551-559). The chemistry involves the addition of Ni(II) to the
His6 tag, followed by oxidation of the metal with a peracid. It is shown here
that, in addition to the His6 tag, a tyrosine residue placed in close proximity
to the metal-binding site can strongly stimulate the yield of cross-linked
product. This finding has important practical implications in the use of the His6
Ni-based cross-linking reaction for the analysis of multiprotein complexes.
PMID- 9642144
TI - Identification of the hydrophobic amino acid residues required for heme assembly
in the rhizobial oxygen sensor protein FixL.
AB - Rhizobial FixL is a novel heme protein, which senses environmental oxygen tension
and directs signal transduction via protein phosphotransfer. To identify the
essential residues for heme assembly in Rhizobium meliloti FixL, we individually
replaced the 18 invariant hydrophobic amino acid residues (F, I, L, and V) in the
heme-containing domain with alanine and histidine. Spectroscopic measurements of
the soluble fractions from fixL recombinant Escherichia coli revealed that V152,
F162, F170, I172, L185, F226, L230, and F243 as well as the proximal ligand H194
were indispensable for heme assembly. Autoxidation rates of purified I209H,
I210A, and I210H were 65-fold, 15-fold, and 15-fold, respectively, faster than
that of the wild type, although they retained heme in the protein. The absorption
peak in the Soret region of the ferric I209H or I210H was red-shifted, suggesting
that the ferric heme is a hexa-coordinate form in these mutants.
PMID- 9642145
TI - Long-term postmortem survival of mitochondrial genomes in mouse synaptosomes and
their rescue in a mitochondrial DNA-less mouse cell line.
AB - Mitochondrial DNA (mtDNA) transfer was carried out from postmortem mouse tissues
to mouse mtDNA-less (rho0) cells to determine how long it takes for autolysis of
mtDNA after death and whether mtDNA in postmortem tissues can recover its
function in rho0 cells. The results showed that mtDNA was stable in postmitotic
tissues stored at 4 degreesC. Moreover, mtDNA in postmortem brain tissues stored
for up to 1 month still retained functional properties, causing complete recovery
of mitochondrial respiratory function, when it was transferred to rho0 cells.
These observations suggest that mtDNA in brain tissue can survive for 1 month
after death and can start replication and gene expression in rho0 cells without
showing any functional defects. This procedure might be applied to human autopsy
brain tissues for examination of the influence of accumulated somatic mutations
in mtDNA from aged subjects.
PMID- 9642146
TI - Induction of apoptosis in murine macrophages by Mycobacterium tuberculosis is
reactive oxygen intermediates-independent.
AB - Infection with Mycobacterium tuberculosis induces apoptosis in murine macrophage
lines. Resistant macrophages B10R (Bcgr) are more prone to undergo apoptosis than
susceptible B10S (Bcgs) macrophages. Apoptosis and inhibition of intracellular
growth of the mycobacteria seem to be dependent on the production of nitric
oxide, since both can be reverted by aminoguanidine (AMG). Although B10R
macrophages produce more superoxide anion than B10S macrophages after infection
with M. tuberculosis, reactive oxygen intermediate (ROIs) scavengers did not
affect uptake of 3H-uracil incorporation by the mycobacteria nor the induction of
apoptosis. These results further suggest that both phenomena are dependent on the
production of nitric oxide by the infected macrophages.
PMID- 9642147
TI - Lack of protection against oxidative modification of LDL by avian HDL.
AB - Human and murine high density lipoprotein (HDL) has previously been shown to
decrease the accumulation of lipid peroxides on low density lipoprotein (LDL)
under oxidising conditions. Several lines of evidence, including the
ineffectiveness of HDL from paraoxonase knockout mice, suggest that paraoxonase
(PON1) located on HDL is responsible for its protective effect against lipid
peroxidation. In this report we compare the effect of HDL from chicken, turkey
and ostrich with human HDL on lipid peroxidation of LDL. Avian serum lacked PON1
activity and PON1 immunoactivity was also absent by ELISA and Western blotting
whereas all three techniques detected PON1 in a variety of non-avian species
(cow, guinea-pig, rat, sheep, mouse, hamster, monkey and rabbit). Platelet
activating factor acetyl hydrolase (PAFAH) activity was also absent from avian
serum. Avian HDL isolated from plasma when incubated with human LDL was
ineffective in preventing the Cu2+-induced accumulation of lipid peroxides on
this lipoprotein whereas human HDL under the same conditions was highly effective
in this respect. Avian LDL was much more resistant to oxidation than human LDL,
perhaps explaining the lack of HDL-PON1 and PAFAH. We conclude that these
findings provide further evidence than PON1 has an important role in the
antiatherogenic/anti-inflammatory effects of HDL and that avian HDL can provide a
valuable model which complements the use of HDL from paraoxonase knockout mice in
the investigation of PON1 and PAFAH.
PMID- 9642148
TI - KDEL motif interacts with a specific sequence in mammalian erd2 receptor.
AB - The ER retention of lumenal proteins is achieved by a process which involves
binding of escaped proteins via the C-terminal KDEL-tags to a KDEL receptor (erd2
receptor) in a post-ER compartment and return of the protein-receptor complex
back to the ER. The transmembrane topology of the human KDEL receptor, which is
an integral membrane protein, has been proposed. We have synthesised sets of
cellulose-bound overlapping peptides covering the complete se quence of the
receptor to study the interaction of the erd2 receptor with lumenal ER proteins,
CaBP1 and CaBP2. At the next stage, the proposed lumenal loops of the receptor
were more closely mapped. A short sequence, essential for the protein binding to
the most efficient binding site of the receptor, was identified as 22KIWK25,
which is in accordance with one of the proposed structural models of the
receptor. The binding was of high specificity and was almost completely inhibited
by KDEL-containing soluble peptides. The phosphorylation state of CaBP1/CaBP2 did
not affect their binding to the KDEL receptor.
PMID- 9642149
TI - Detection and analysis of four polymorphic markers at the human monoamine oxidase
(MAO) gene in Japanese controls and patients with Parkinson's disease.
AB - Monoamine oxidase (MAO), which exists in two forms (MAOA and MAOB), plays an
important role in the oxidative metabolism of neurotransmitters such as dopamine,
and has been implicated in the etiology of Parkinson's disease (PD). Individual
variations in the activity of these enzymes appear to be genetically determined,
and these genetic variations appear to be predominantly mediated by the MAO
locus. Here, we detected and analyzed four polymorphic markers in the MAO gene
using a polymerase chain reaction method in 228 Japanese controls (102 males and
126 females) and 68 patients with PD (30 males and 38 females). Although the
analysis of the MAOA marker demonstrated no overall association between its
alleles and PD, a significant difference in the frequency of one particular MAOA
allele between controls and patients with PD was found. Moreover, in a comparison
of the distribution of the full haplotypes at the MAOA locus, there was a
significant difference in the frequency of one particular haplotype between male
controls and patients with PD. In the MAOB polymorphism, there was no difference
in the distribution of alleles between them. These findings support the
hypothesis that the MAOA gene may affect the susceptibility of individuals to PD
among MAOA polymorphic loci.
PMID- 9642150
TI - pp120, a substrate of the insulin receptor tyrosine kinase, is associated with
phosphatase activity.
AB - pp120, a plasma membrane glycoprotein, is phosphorylated on Tyr488 by the insulin
receptor tyrosine kinase. This requires basal phosphorylation on Ser503 by cAMP
dependent serine kinase. Phe513, the other tyrosine residue in the intracellular
domain, does not undergo insulin-stimulated phosphorylation. Phe488 mutation
abolished basal and insulin-stimulated phosphorylation, whereas, Phe513 plus
Phe488 mutation markedly decreased the effect of insulin on pp120 phosphorylation
without altering basal phosphorylation in intact cells. To investigate whether
basal phosphorylation of pp120 is regulated by a phosphatase activity that
requires Tyr513, in vitro phosphorylation assays using partially purified
glycoproteins from stably transfected NIH 3T3 cells were performed in the absence
of phosphatase inhibitors. Wild-type pp120 was promptly dephosphorylated,
whereas, Y513F pp120 was not. Decreasing pp120 expression by antisense cDNA
transfection proportionally decreased phosphatase activity in H4-II-E hepatoma
cells measured by the p-nitrophenyl phosphate assay. This suggests that pp120 is
associated with phosphatase activity that requires an intact Tyr513 residue.
PMID- 9642151
TI - Calcium-independent activation of extracellular signal-regulated kinases 1 and 2
by cyclic strain.
AB - We have previously demonstrated that cyclic strain induces extracellular signal
regulated kinases 1 and 2 (ERK1/2) activation in endothelial cells (EC). The aim
of this study was to investigate the effect of Ca2+ on the activation of ERK1/2.
Bovine aortic EC were pretreated with a chelator of extracellular Ca2+,
ethylaneglycol-bis(aminoethylether)-tetra-acetate (EGTA), a depleter of Ca2+
pools, 2,5-Di-(tert-butyl)-1,4-benzohydroquinone (BHQ), or a Ca2+ channel
blocker, GdCl3, and subjected to an average 10 % strain at a rate of 60
cycles/min for 10 min. BHQ and GdCl3 did not inhibit the strain-induced ERK1/2
activation. Chelation of normal extracellular Ca2+ (1.8 mM) medium with EGTA (3
mM) acutely stimulated baseline phosphorylation and activation of ERK1/2, thereby
obscuring any strain-induced activation of ERK1/2. However, in EC preincubated
for 24 hours in Ca2+-free medium, elevated baseline phosphorylation was minimally
activated by EGTA (200 microM) such that cyclic strain stimulated ERK1/2 in the
presence or absence of BHQ. These results suggest a Ca2+ independence of the
ERK1/2 signaling pathway by cyclic strain.
PMID- 9642152
TI - Alternative splicing of the mRNA coding for the human endothelial angiotensin
converting enzyme: a new mechanism for solubilization.
AB - Angiotensin converting enzyme (ACE) is a zinc metalloprotease anchored in the
plasma membrane with a carboxy-terminal hydrophobic domain. In addition, the
existence of a soluble form of ACE lacking the transmembrane domain has been
reported. We show evidence for the existence of an mRNA specific for this isoform
produced by alternative splicing. In human umbilical vein endothelial cells, two
ACE mRNAs of different length (4.3 and 3.5 kb) were detected by Northern blot.
Ribonuclease protection assays and the sequence of a PCR-amplified cDNA fragment
show that the shortened ACE mRNA lacks the exons coding for the transmembrane
domain of the protein. As this mRNA could be the source of soluble ACE, plasma
ACE activity may be regulated on the level of mRNA processing.
PMID- 9642153
TI - Effect of eicosapentaenoic acid on glucose-induced diacylglycerol synthesis in
cultured bovine aortic endothelial cells.
AB - Hyperglycemia has been postulated to increase diacylglycerol (DAG) level through
de novo synthesis pathway and subsequently activate protein kinase C (PKC) in
vascular cells, possibly leading to vascular dysfunction associated with
diabetes. In this study, we examined the effect of eicosapentaenoic acid (EPA) on
high glucose-induced increase in DAG level in cultured aortic endothelial cells
(ECs). In ECs, total DAG level was significantly increased in the cells cultured
with high glucose levels (400 mg/dl) compared with the cells with normal glucose
levels (100 mg/dl). The addition of EPA completely prevented high glucose-induced
increase in total DAG level. In contrast, other common fatty acids such as
palmitate and oleate significantly stimulated DAG syntheisis, although
arachidonate did not affect it. High glucose level significantly stimulated the
incorporation of 3H-palmitate into DAG, while it did not affect the incorporation
of 3H-arachidonate into DAG. The addition of EPA completely prevented the high
glucose-induced increase in 3H-palmitate incorporation into DAG, while it did not
affect the 3H-arachidonate incorporation. These findings suggest that EPA can
prevent high glucose induced-increase in DAG level in ECs, probably by
specifically inhibiting de novo synthesis at the step of acylation. EPA may be
one of the candidates for clinical agents normalizing activation of DAG-PKC
pathway in diabetic vascular tissues and preventing vascular complications
associated with diabetes.
PMID- 9642154
TI - Nonylphenol ethoxylates, but not nonylphenol, are substrates of the human
multidrug resistance P-glycoprotein.
AB - Alkylphenol ethoxylates are surfactants that are commonly used in industry and in
home care products. They are broken down by anaerobes to yield toxic
environmental pollutants such as nonylphenol. In this study, we tested whether
nonylphenol ethoxylates and their most common biodegradation product,
nonylphenol, were substrates of human P-glycoprotein. In vivo and in vitro assays
showed that the enzyme interacts with a wide variety of nonylphenol ethoxylate
compounds, but not with nonylphenol. These results suggest that P-glycoprotein
can protect organisms from the toxic and estrogenic effects of nonylphenol
ethoxylates, but not from the major biodegradation product, nonylphenol.
PMID- 9642155
TI - Studies on the mechanism of oxidative modification of human glyceraldehyde-3
phosphate dehydrogenase by glutathione: catalysis by glutaredoxin.
AB - In this report the protein human glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
has been examined to clarify the roles of (a) direct oxidation and (b) thiol
disulphide exchange (with glutathione disulphide) on the modification of its
catalytic activity. An in vitro system using purified human GAPDH and [35S]-GSSG
(glutathione disulphide), has permitted clarification of these possibilities by
showing that S-glutathionylation of GAPDH does not result in an inactivation of
the enzyme. Rather, the direct oxidation of GAPDH with hydrogen peroxide is
responsible for inhibition of the catalytic activity of the protein. Furthermore,
pre-treatment of the enzyme with hydrogen peroxide enhances the formation of
glutathione-GAPDH mixed disulphides in the presence of glutathione disulphide.
This may serve as a molecular "switch" directing the protein to other reported
functions in the cell. It is also shown that the efficiency of S
glutathionylation of either native or oxidised GAPDH is enhanced by the presence
of recombinant glutaredoxin (thiol transferase) of either bacterial or human
origin. Under the conditions of analysis the glutaredoxin itself is also shown to
readily undergo S-glutathionylation external to its active site. Taken together,
the data indicate the complexity of mechanisms likely to be involved in
regulating cellular proteins during oxidative stress and implicate controlled
enzyme-catalysed S-glutathionylation as a potential selectivity factor in the
redox modification of protein function by glutathione.
PMID- 9642156
TI - Association of insulin receptor substrate 3 with SH2 domain-containing proteins
in rat adipocytes.
AB - We have recently purified and cloned a new member of the insulin receptor
substrate family, designated insulin receptor substrate 3 (IRS-3), from rat
adipocytes. The amino acid sequence of IRS-3 shows multiple potential sites for
tyrosine phosphorylation in motifs which engage specific SH2 domain-containing
proteins. In order to determine which SH2 domain proteins complex with IRS-3, we
have searched for coimmunoprecipitation from lysates of untreated and insulin
stimulated adipocytes. Phosphatidylinositol 3-kinase and the tyrosine phosphatase
SHP-2 complexed with the tyrosine phosphorylated form of IRS-3, whereas the
phospholipase Cgamma did not, and the adaptor Grb2 did so to a much lesser
extent. These findings complete the survey of SH2 domain proteins associated with
each of the four known members of the IRS family and provide the framework for
further analysis of the role of IRS-3 in insulin signaling.
PMID- 9642157
TI - Cyclic glucans produced by the intramolecular transglycosylation activity of
potato D-enzyme on amylopectin.
AB - Potato D-enzyme catalyses an intramolecular transglycosylation reaction on
amylose to produce cycloamylose, a novel cyclic alpha-1, 4 glucan. To determine
if a similar activity could be observed with a high molecular weight branched
substrate, recombinant potato D-enzyme was incubated with amylopectin. The
substrate was converted into two fractions of lower molecular mass. Fraction I
comprised 15% cyclic molecules of which the majority contained both alpha-1,4 and
alpha-1,6 links. These were shown to be branched molecules with branches shorter
than those in amylopectin. Fraction II comprised 80% cyclic molecules of which
the majority contained only alpha-1,4 links (cycloamylose). Since fraction II
appeared before fraction I, we propose that D-enzyme first catalysed the
cyclisation of the outer side chains of amylopectin and then the cyclisation of
inner chains to produce branched clusters. These results demonstrate that D
enzyme can catalyse the transfer of branched glucans, and suggest novel ways in
which it may participate in starch metabolism in plants.
PMID- 9642159
TI - Inter-organ leptin exchange in humans.
AB - To assess the individual role of splanchnic organs, kidney, and peripheral
tissues on leptin metabolism, leptin exchange across the splanchnic bed, kidney,
and leg has been evaluated by the arterio-venous technique in post-absorptive non
obese subjects. Leptin levels in the hepatic and renal veins were significantly
lower (p < 0.001), while femoral vein levels were consistently greater (p < 0.05)
than in the artery. The fractional extraction of leptin, namely the percentage of
arterial leptin extracted, was greater in splanchnic organs (16%) than in the
kidney (9.5%). Urinary excretion of leptin was undetectable in most subjects,
indicating that leptin is degraded within the kidney. There was no correlation
between fractional extraction of leptin and glomerular filtration rate, whereas
leptin fractional extraction was directly related to renal plasma flow (p =
0.017). Renal leptin clearance was about 50% of the glomerular filtration rate.
Our data demonstrate that both splanchnic organs and the kidney cooperate in the
disposal of leptin, while peripheral tissues add significant amounts of leptin to
the circulation. In non-obese subjects the contribution of the kidney to whole
body clearance is no more than 50%. The removal of leptin by the kidney depends
on renal plasma flow but not on glomerular filtration rate or filtered leptin.
PMID- 9642158
TI - Up-regulation of uncoupling protein 3 (UCP3) mRNA by exercise training and down
regulation of UCP3 by denervation in skeletal muscles.
AB - In skeletal muscles, increased utilization of lipids and carbohydrates
accompanied with increased energy expenditure has been observed during and after
exercise. UCP3, mitochondrial uncoupling protein, is expressed in skeletal
muscles. We investigated UCP3 mRNA levels in exercise training mice which
increased energy expenditure and in sciatic nerve-denervated mice which decreased
energy expenditure. Mice exercised by 2 wk swimming had 14- to 18-fold increases
of UCP3 mRNA in skeletal muscles 3 h after the last swimming, but no increases of
UCP1 mRNA in BAT and of UCP2 mRNA in WAT. However, 22 h after exercise, UCP3 mRNA
increases observed in skeletal muscles 3 h after exercise returned to sedentary
levels. Similar transient increases of UCP3 mRNA were observed in 1 wk treadmill
running training or a single exercise bout. In denerved gastrocnemius, GLUT4 and
UCP3 mRNA decreased by 58 and 45%, respectively. These data indicate that UCP3
may have a role for fine adjustments of energy expenditure and that up-regulation
of UCP3 mRNA may be a defense mechanism against extra energy supply to consume
extra energy in skeletal muscles.
PMID- 9642161
TI - Specific detection of sialyl Lewis X determinant carried on the mucin GlcNAcbeta1
->6GalNAcalpha core structure as a tumor-associated antigen.
AB - Sialyl Lewis X serves as a ligand for selectins and is proposed to be implicated
in hematogenous metastasis of cancers. When a cultured human breast cancer cell
line, MCF-7, which does not express sialyl Lewis X, was transfected with human
fucosyltransferase VI cDNA, a strong expression of sialyl Lewis X was induced on
transfectant cells. The transfectant cells were found to be also reactive to the
antibody NCC-ST-439, which was initially raised against human gastric cancer
cells and later was shown to recognize a tumor-associated carbohydrate antigen in
breast, gastric, and colon cancers. This suggested that the antigen recognized by
NCC-ST-439 is closely related to sialyl Lewis X. Subsequent studies indicated
that NCC-ST-439 specifically reacts to NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-
>3)GlcNAcbet a1-->6GalNAcalpha1 -->R, the sialyl Lewis X on the mucin GlcNAcbeta1
->6 GalNAcalpha structure. The antibody was not reactive to the conventional
sialyl Lewis X determinants on straight and/or branched polylactosamine
structures including NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-->3)GlcNAcbet a1-
>3Galbeta1-->4 Glcbeta1-->R and NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-
>3)GlcNAcbet a1-->6Galbeta1-->4 Glcbeta1-->R. This was in clear contrast to most
of the known anti-sialyl Lewis X antibodies, which do not discriminate internal
structures carrying the sialyl Lewis X determinant. On the other hand, the newly
generated monoclonal antibody GSC154-27 had a specificity completely the reverse
of the specificity of NCC-ST-439 in that it was strongly reactive to the
conventional sialyl Lewis X determinants in straight and branched polylactosamine
structures, while far less reactive to the sialyl Lewis X determinant on the
mucin GlcNAcbeta1-->6GalNAcalpha core structure. A set of these two antibodies
would be useful in discriminating the molecular species of sialyl Lewis X
expressed by malignant cells and in studying their functional significance.
PMID- 9642160
TI - Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the
peripheral blood leukocytes of asthmatics.
AB - Leukotrienes are a family of arachidonic acid metabolites with potent biological
activities such as bronchoconstriction and leukocyte chemotaxis. Recent evidence
has demonstrated that the 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating
protein (FALP) products of arachidonic acid metabolism, leukotriene C4, D4 and
E4, were increased in the serum and the urine of asthmatic patients. Therefore,
we examined the expression of 5-LO and FLAP mRNAs in the peripheral blood
leukocytes (PBL) of 10 asthmatics and 10 controls. Both 5-LO and FLAP mRNAs of
PBL in the asthmatic group were found to be significantly increased compared with
those in the control group. These data suggest that up-regulation of 5-LO and
FLAP mRNAs might be involved in the increased leukotriene synthesis and play an
important role in the pathogenesis of asthma.
PMID- 9642162
TI - Phosphorylation of alphaB-crystallin and HSP27 is induced by similar stressors in
HeLa cells.
AB - Three members of the small heat shock protein family, alphaA-, alphaB-crystallin,
and HSP27, confer thermoresistance upon their overexpression in mammalian cells.
Phosphorylation, in conjunction with the molecular chaperone-like activity of
these small HSPs, is believed to be important for this in situ functional
property. We here report the influence of heat shock and other kinds of stress on
the phosphorylation of alphaA-, alphaB-crystallin, and HSP27 in stably
transfected HeLa cells. It is observed that alphaB-crystallin becomes
phosphorylated upon exposure to the same inducers as is HSP27, although to a
lesser extent. In contrast, phosphorylation of alphaA-crystallin is very low upon
heat stress and even absent when other stressors are used. This indicates that
phosphorylation is not in all instances essential for the stress protective
functioning of the various small HSPs.
PMID- 9642163
TI - Interleukin-2 induces N-glycosylation in T-cells: characterization of human
lymphocyte oligosaccharyltransferase.
AB - We have investigated the enzyme mediating N-glycosylation in "resting" and
activated lymphocytes. Normal peripheral blood lymphocytes (PBLs) were found to
have low activity for glycosylation of a synthetic glycan acceptor peptide. N
glycosylation activity increased 10-fold after mitogen activation of PBLs. N
glycosylation activity remained elevated during long-term culture and expansion
of human lymphocytes when growth was supported by interleukin-2. To our
knowledge, this is the first biochemical evidence for induction of endoplasmic
reticulum functions during T-cell activation. The enzyme mediating N
glycosylation in lymphocytes was localized predominantly but not entirely to a
microsomal organelle by subcellular fractionation. After solubilization and 85
fold purification from salt-washed microsomes, the enzyme preparation contained
four predominant proteins. N-terminal sequence analysis identified the proteins
as ribophorin I, ribophorin II (doublet), and a 50-kDa homologue of Wbp1, a yeast
protein essential for N-glycosylation.
PMID- 9642166
TI - Introduction: Processing eukaryotic mRNAs.
PMID- 9642164
TI - Synergistic activation of transcription by physiologically unrelated
transcription factors through cooperative DNA-binding.
AB - Most eukaryotic promoters contain binding sites for several different
transcription factors, which often act synergistically. Mechanistically, synergy
is ascribed either to cooperative DNA-binding of the factors to the promoter or
to some type of "multiple contact" mechanism in which each activator performs a
different task in stimulating the transcription machinery. Here, it is shown that
the yeast activators Gal4 and Put3 bind to DNA cooperatively in vivo and can
activate transcription synergistically from certain synthetic promoters.
Normally, Gal4 and Put3 bind to completely different promoters and activate
physiologically unrelated sets of genes and it is extremely unlikely that they
have evolved direct protein-protein contacts. These studies add to a growing body
of evidence that binding of proteins to nearby sites in chromatin is
intrinsically cooperative and suggest that many examples of synergy ascribed to
multiple contact mechanisms may instead involve non-traditional cooperative DNA
binding.
PMID- 9642167
TI - RNA localization in Xenopus oocytes.
AB - The transport and localization of mRNAs within Xenopus oocytes contributes to an
asymmetry that determines axis formation in the embryo. Several mRNAs become
localized along the animal-vegetal axis. The mitochondrial cloud, a specialized
cytoplasmic compartment which contributes to the formation of germ plasm, and the
endoplasmic reticulum play important roles in sorting and localizing these RNAs.
As in other species and cell types, the localization of RNAs in Xenopus oocytes
is directed by signals in the 3' untranslated regions of the transcripts.
Cytoplasmic proteins that interact with these signals are being identified, as
are the links between RNA localization, intracellular organelles and early
embryonic development.Copyright 1997 Academic Press Limited.
PMID- 9642168
TI - Control of mRNA stability and translation during Drosophila development.
AB - Translational control of mRNAs regulates the spatio- temporal production of the
proteins they encode. Further refinement of mRNA and protein distribution
patterns is brought about by regulation of transcript stability. Genetic and
molecular analyses in Drosophila can provide unparalleled insight into the
developmental functions of the modulation of mRNA translation and stability.
These mechanisms play a key role in regulating the production of cell fate
determinants, cell cycle regulators and molecular chaperones.Copyright 1997
Academic Press
PMID- 9642169
TI - Translational control of development in C. elegans.
AB - Translational control by the 3'untranslated regions (3'UTRs) of mRNAs contributes
to important events throughout the development of C. elegans. In oocytes and
early embryos, maternal mRNAs are controlled by 3'UTR elements to restrict
translation of their protein products to specific blastomeres. Localized
translation is probably critical for specifying blastomere identity. In both
germline and somatic cells, mRNAs from sex determining genes are translationally
repressed by 3'UTR controls. These controls balance the activities that specify
male and female cell fates. During larval development, the temporal sequence of
cell lineages requires 3'UTR-mediated regulation of heterochronic genes by a
small non-protein coding RNA. We review what is known about these translational
control mechanisms in C. elegans. This overview illustrates that translational
control by 3'UTR elements is a powerful mechanism for regulating the expression
of multiple gene products in diverse cell types during development of a multi
cellular animal.Copyright 1997 Academic Press Limited.
PMID- 9642170
TI - Novel functions for 'nuclear factors' in the cytoplasm: the Sex-lethal paradigm.
AB - In recent years, novel functions for a number of nuclear factors have been
uncovered in the cytoplasm, mainly at the level of translation. These factors
behave as multifunctional regulators of gene expression and many play key roles
in cell differentiation and development. One of the best characterized examples
is that of Sex-lethal (SXL), an RNA-binding protein that is expressed in female
Drosophila flies and controls sex determination and dosage compensation. Recent
findings indicate that SXL, a paradigmatic regulator of splicing, also controls
translation of target mRNAs. This review attempts to summarize this evidence and
provide an overview of 'nuclear factors' with roles in translation.Copyright 1998
Academic Press Limited
PMID- 9642171
TI - The U7 snRNP and the hairpin binding protein: Key players in histone mRNA
metabolism.
AB - Animal replication-dependent histone mRNAs are subject to several post
transcriptional regulatory processes. Their non-polyadenylated 3' ends are formed
preferentially during S phase by a unique nuclear cleavage event. This requires
the base pairing between U7 snRNA and a histone spacer element 3' of the cleavage
site. Cleavage occurs preferentially after adenosine, at a fixed distance from
the hybrid region. A conserved RNA hairpin just upstream of the cleavage site is
recognised by the hairpin binding protein (HBP) that acts as an auxiliary
processing factor, stabilising the interaction of the histone pre-mRNA with the
U7 snRNP. The interaction between HBP and the RNA hairpin is very stable and HBP
is also found associated with histone mRNAs on polysomes. The hairpin and
presumably, HBP are also required for nuclear export and translation of histone
mRNA. Furthermore, histone mRNAs are selectively destabilised in the G2 phase or
upon inhibition of DNA synthesis and this regulation is also associated with the
hairpin. Recently, HBP-encoding cDNAs were isolated from various organisms.
Human, mouse and Xenopus laevis HBPs are similar, while the Caenorhabditis
elegans protein has significant homology to the others only in a central RNA
binding domain.Copyright 1997 Academic Press Limited
PMID- 9642172
TI - The role of elav-like genes, a conserved family encoding RNA-binding proteins, in
growth and development.
AB - The elav gene is the prototype for a developmental regulator encoding a tissue
specific RNA-binding protein. The family of elav-like genes includes multiple
members that are expressed in the nervous system at different times during
development and also one that is expressed in all tissues. The elav-like proteins
are proposed to function by binding to specific mRNAs and regulating their
expression to control a developmental program. Consistent with this model, the
overexpression of some elav-like genes results in an alteration in the
developmental fates of some cells. Potential mRNA targets for these proteins have
been identified along with functions in alternative RNA processing, cytoplasmic
polyadenylation, and mRNA stability. This diversity of post-transcriptional
regulatory events may be due to combinatorial interactions with other RNA-binding
proteins and multiple effectors of RNA regulation.Copyright 1997 Academic Press
Limited
PMID- 9642173
TI - Introduction: Proteolytic maturation of secretory proteins.
PMID- 9642174
TI - Introduction: Adaptation mechanisms.
PMID- 9642175
TI - Introduction: The green signal for plant pattern formation.
PMID- 9642176
TI - Information processing by RNA polymerase: recognition of regulatory signals
during RNA chain elongation.
PMID- 9642177
TI - Establishment of prespore-specific gene expression in Bacillus subtilis:
localization of SpoIIE phosphatase and initiation of compartment-specific
proteolysis.
AB - Immunofluorescence microscopy was used to study the establishment of compartment
specific transcription during sporulation in Bacillus subtilis. Analysis of the
distribution of the anti-anti-sigma factor, SpoIIAA, in a variety of mutant
backgrounds supports a model in which the SpoIIE phosphatase, which activates
SpoIIAA by dephosphorylation, is sequestered onto the prespore face of the
asymmetric septum. Thus, prespore-specific gene expression apparently arises as a
result of the compartmentalization of SpoIIE protein. The results also suggest
the existence of at least two compartment-specific programs of proteolysis, one
dependent on the mother cell-specific sigma factor sigma E and the other
dependent on the prespore-specific sigma factor sigma F.
PMID- 9642178
TI - A complex pattern of traveling stripes is produced by swimming cells of Bacillus
subtilis.
AB - Motile cells of Bacillus subtilis inadvertently escaped from the surface of an
agar disk that was surrounded by a fluid growth medium and formed a migrating
population in the fluid. When viewed from above, the population appeared as a
cloud advancing unidirectionally into the fresh medium. The cell population
became spontaneously organized into a series of stripes in a region behind the
advancing cloud front. The number of stripes increased progressively until a
saturation value of stripe density per unit area was reached. New stripes arose
at a fixed distance behind the cloud front and also between stripes. The spacing
between stripes underwent changes with time as stripes migrated towards and away
from the cloud front. The global pattern appeared to be stretched by the
advancing cloud front. At a time corresponding to approximately two cell
doublings after pattern formation, the pattern decayed, suggesting that there is
a maximum number of cells that can be maintained within the pattern. Stripes
appear to consist of high concentrations of cells organized in sinking columns
that are part of a bioconvection system. Their behavior reveals an interplay
between bacterial swimming, bioconvection-driven fluid motion, and cell
concentration. A mathematical model that reproduces the development and dynamics
of the stripe pattern has been developed.
PMID- 9642179
TI - Transcriptional analysis of essential genes of the Escherichia coli fatty acid
biosynthesis gene cluster by functional replacement with the analogous Salmonella
typhimurium gene cluster.
AB - The genes encoding several key fatty acid biosynthetic enzymes (called the fab
cluster) are clustered in the order plsX-fabH-fabD-fabG-acpP-fabF at min 24 of
the Escherichia coli chromosome. A difficulty in analysis of the fab cluster by
the polar allele duplication approach (Y. Zhang and J. E. Cronan, Jr., J.
Bacteriol. 178:3614-3620, 1996) is that several of these genes are essential for
the growth of E. coli. We overcame this complication by use of the fab gene
cluster of Salmonella typhimurium, a close relative of E. coli, to provide
functions necessary for growth. The S. typhimurium fab cluster was isolated by
complementation of an E. coli fabD mutant and was found to encode proteins with >
94% homology to those of E. coli. However, the S. typhimurium sequences cannot
recombine with the E. coli sequences required to direct polar allele duplication
via homologous recombination. Using this approach, we found that although
approximately 60% of the plsX transcripts initiate at promoters located far
upstream and include the upstream rpmF ribosomal protein gene, a promoter located
upstream of the plsX coding sequence (probably within the upstream gene, rpmF) is
sufficient for normal growth. We have also found that the fabG gene is
obligatorily cotranscribed with upstream genes. Insertion of a transcription
terminator cassette (omega-Cm cassette) between the fabD and fabG genes of the E.
coli chromosome abolished fabG transcription and blocked cell growth, thus
providing the first indication that fabG is an essential gene. Insertion of the
omega-Cm cassette between fabH and fabD caused greatly decreased transcription of
the fabD and fabG genes and slower cellular growth, indicating that fabD has only
a weak promoter(s).
PMID- 9642180
TI - Anaerobic regulation of Bacillus subtilis Krebs cycle genes.
AB - Krebs cycle enzyme activity in Bacillus subtilis was examined under aerobic and
anaerobic conditions. Citrate synthase and aconitase activities in cells grown
anaerobically in the presence of nitrate were reduced by as much as 10- and 30
fold, respectively, from levels observed under aerobic culture conditions. The
maximum level of isocitrate dehydrogenase activity during anaerobic growth was
only twofold lower than that in aerobic cultures. These reductions in activity
under conditions of anaerobiosis were found to be primarily the result of reduced
Krebs cycle gene transcription. This repression was not dependent on either the
fnr or resDE gene products, which have been shown to regulate expression of other
B. subtilis genes in response to anaerobic conditions. Additionally, catabolite
control proteins CcpA and CcpB were not responsible for the repression. A dyad
symmetry element located between positions -73 and -59 relative to the
transcription start site of the aconitase gene (citB) promoter was previously
shown to be a target of catabolite repression and the binding site for a putative
negative regulator during aerobic growth. The deletion of the upstream arm of the
dyad symmetry region abolished the citB repression observed during anaerobic
growth. Furthermore, neither citZ or citB was repressed in an anaerobically grown
citB mutant, an effect that was very likely the result of citrate accumulation.
These results suggest that catabolite repression and anaerobic repression of citZ
and citB are regulated by a common mechanism that does not involve CcpA, CcpB,
Fnr, or ResDE.
PMID- 9642181
TI - Purification and properties of the F1F0 ATPase of Ilyobacter tartaricus, a sodium
ion pump.
AB - The ATPase of Ilyobacter tartaricus was solubilized from the bacterial membranes
and purified. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the
purified enzyme revealed the usual subunit pattern of a bacterial F1F0 ATPase.
The polypeptides with apparent molecular masses of 56, 52, 35, 16.5, and 6.5 kDa
were identified as the alpha, beta, gamma, epsilon, and c subunits, respectively,
by N-terminal protein sequencing and comparison with the sequences of the
corresponding subunits from the Na(+)-translocating ATPase of Propionigenium
modestum. Two overlapping sequences were obtained for the polypeptides moving
with an apparent molecular mass of 22 kDa (tentatively assigned as b and delta
subunits). No sequence could be determined for the putative a subunit (apparent
molecular mass, 25 kDa). The c subunits formed a strong aggregate with the
apparent molecular mass of 50 kDa which required treatment with trichloroacetic
acid for dissociation. The ATPase was inhibited by dicyclohexyl carbodiimide, and
Na+ ions protected the enzyme from this inhibition. The ATPase was specifically
activated by Na+ or Li+ ions, markedly at high pH. After reconstitution into
proteoliposomes, the enzyme catalyzed the ATP-dependent transport of Na+, Li+, or
Hi+. Proton transport was specifically inhibited by Na+ or Li+ ions, indicating a
competition between these alkali ions and protons for binding and translocation
across the membrane. These experiments characterize the I. tartaricus ATPase as a
new member of the family of FS-ATPases, which use Na+ as the physiological
coupling ion for ATP synthesis.
PMID- 9642182
TI - Gene replacement analysis of the Streptomyces virginiae barA gene encoding the
butyrolactone autoregulator receptor reveals that BarA acts as a repressor in
virginiamycin biosynthesis.
AB - Virginiae butanolides (VBs), which are among the butyrolactone autoregulators of
Streptomyces species, act as a primary signal in Streptomyces virginiae to
trigger virginiamycin biosynthesis and possess a specific binding protein, BarA.
To clarify the in vivo function of BarA in the VB-mediated signal pathway that
leads to virginiamycin biosynthesis, two barA mutant strains (strains NH1 and
NH2) were created by homologous recombination. In strain NH1, an internal 99-bp
EcoT14I fragment of barA was deleted, resulting in an in-frame deletion of 33
amino acid residues, including the second helix of the probable helix-turn-helix
DNA-binding motif. With the same growth rate as wild-type S. virginiae on both
solid and liquid media, strain NH1 showed no apparent changes in its
morphological behavior, indicating that the VB-BarA pathway does not participate
in morphological control in S. virginiae. In contrast, virginiamycin production
started 6 h earlier in strain NH1 than in the wild-type strain, demonstrating for
the first time that BarA is actively engaged in the control of virginiamycin
production and implying that BarA acts as a repressor in virginiamycin
biosynthesis. In strain NH2, an internal EcoNI-SmaI fragment of barA was replaced
with a divergently oriented neomycin resistance gene cassette, resulting in the C
terminally truncated BarA retaining the intact helix-turn-helix motif. In strain
NH2 and in a plasmid-integrated strain containing both intact and mutated barA
genes, virginiamycin production was abolished irrespective of the presence of VB,
suggesting that the mutated BarA retaining the intact DNA-binding motif was
dominant over the wild-type BarA. These results further support the hypothesis
that BarA works as a repressor in virginiamycin production and suggests that the
helix-turn-helix motif is essential to its function. In strain NH1, VB production
was also abolished, thus indicating that BarA is a pleiotropic regulatory protein
controlling not only virginiamycin production but also autoregulator
biosynthesis.
PMID- 9642183
TI - Efflux pumps involved in toluene tolerance in Pseudomonas putida DOT-T1E.
AB - The basic mechanisms underlying solvent tolerance in Pseudomonas putida DOT-T1E
are efflux pumps that remove the solvent from bacterial cell membranes. The
solvent-tolerant P. putida DOT-T1E grows in the presence of high concentrations
(e.g., 1% [vol/vol]) of toluene and octanol. Growth of P. putida DOT-T1E cells in
LB in the presence of toluene supplied via the gas phase has a clear effect on
cell survival: the sudden addition of 0.3% (vol/vol) toluene to P. putida DOT-T1E
pregrown with toluene in the gas phase resulted in survival of almost 100% of the
initial cell number, whereas only 0.01% of cells pregrown in the absence of
toluene tolerated exposure to this aromatic hydrocarbon. One class of toluene
sensitive octanol-tolerant mutant was isolated after Tn5-'phoA mutagenesis of
wild-type P. putida DOT-T1E cells. The mutant, called P. putida DOT-T1E-18, was
extremely sensitive to 0.3% (vol/vol) toluene added when cells were pregrown in
the absence of toluene, whereas pregrowth on toluene supplied via the gas phase
resulted in survival of about 0.0001% of the initial number. Solvent exclusion
was tested with 1,2,4-[14C]trichlorobenzene. The levels of radiochemical
accumulated in wild-type cells grown in the absence and in the presence of
toluene were not significantly different. In contrast, the mutant was unable to
remove 1,2,4-[14C]trichlorobenzene from the cell membranes when grown on Luria
Bertani (LB) medium but was able to remove the aromatic compound when pregrown on
LB medium with toluene supplied via the gas phase. The amount of 14C-labeled
substrate in whole cells increased in competition assays in which toluene-and
xylenes were the unlabeled competitors, whereas this was not the case when
benzene was the competitor. This finding suggests that the exclusion system works
specifically with certain aromatic substrates. The mutation in P. putida DOT-T1E
18 was cloned, and the knockedout gene was sequenced and found to be homologous
to the drug exclusion gene mexB, which belongs to the efflux pump family of the
resistant nodulator division type.
PMID- 9642184
TI - Analysis of genes involved in biosynthesis of coronafacic acid, the polyketide
component of the phytotoxin coronatine.
AB - Coronafacic acid (CFA) is the polyketide component of coronatine (COR), a
phytotoxin produced by the plant-pathogenic bacterium Pseudomonas syringae. The
genes involved in CFA biosynthesis are encoded by a single transcript which
encompasses 19 kb of the COR gene cluster. In the present study, the nucleotide
sequence was determined for a 4-kb region located at the 3' end of the CFA
biosynthetic gene cluster. Three open reading frames were identified and
designated cfa8, cfa9, and tnp1; the predicted translation products of these
genes showed relatedness to oxidoreductases, thioesterases, and transposases,
respectively. The translational products of cfa8 and cfa9 were overproduced in
Escherichia coli BL21; however, tnp1 was not translated in these experiments.
Mutagenesis and complementation analysis indicated that cfa8 is required for the
production of CFA and COR. Analysis of a cfa9 mutant indicated that this gene is
dispensable for CFA and COR production but may increase the release of enzyme
bound products from the COR pathway; tnp1, however, had no obvious function in
CFA or COR biosynthesis. A genetic strategy was used to produce CFA in a P.
syringae strain which lacks the COR gene cluster; this approach will be useful in
future studies designed to investigate biosynthetic products of the CFA gene
cluster.
PMID- 9642185
TI - Aeromonas hydrophila adenylyl cyclase 2: a new class of adenylyl cyclases with
thermophilic properties and sequence similarities to proteins from
hyperthermophilic archaebacteria.
AB - Complementation of an Escherichia coli cya mutant with a genomic library from
Aeromonas hydrophila allowed isolation of clones containing two different cya
genes. Whereas one of these genes (cyaA) coded for an adenylyl cyclase (AC1)
belonging to the previously described class I adenylyl cyclases (ACs), the second
one (cyaB) coded for a protein (AC2) that did not match any previously
characterized protein when compared to protein sequence databases. In particular,
it did not align with any of members of the three known classes of ACs. The
purified AC2 enzyme exhibited remarkable biochemical characteristics, namely, an
optimum activity at a high temperature (65 degrees C) and at an alkalinic pH
(9.5). In order to investigate the functions of both cyclases in A. hydrophila,
each gene was inactivated in the chromosome and the resulting mutant strains were
examined for physiological alterations. It was shown that, in contrast to cyaA,
the cyaB gene was not expressed under usual laboratory growth conditions.
However, introduction of a plasmid harboring the cyaB gene in a cyaA mutant, as
well as in a cyaA cyaB mutant, allowed cyclic AMP production. AC2 is the first
member of a new class of previously unrecognized ACs, and to date, no functional
counterpart has been demonstrated in other organisms. However, scanning databases
revealed a significant similarity between AC2 and the gene product of three
hyperthermophilic archaebacteria: Methanobacterium thermoautotrophicum,
Archaeglobus fulgidus, and Methanococcus jannaschii. The possibility of a gene
transfer between such phylogenetically divergent bacteria is discussed.
PMID- 9642186
TI - Induction of the SOS response increases the efficiency of global nucleotide
excision repair of cyclobutane pyrimidine dimers, but not 6-4 photoproducts, in
UV-irradiated Escherichia coli.
AB - Nucleotide excision repair (NER) is responsible for the removal of a variety of
lesions from damaged DNA and proceeds through two subpathways, global repair and
transcription-coupled repair. In Escherichia coli, both subpathways require UvrA
and UvrB, which are induced following DNA damage as part of the SOS response. We
found that elimination of the SOS response either genetically or by treatment
with the transcription inhibitor rifampin reduced the efficiency of global repair
of the major UV-induced lesion, the cyclobutane pyrimidine dimer (CPD), but had
no effect on the global repair of 6-4 photoproducts. Mutants in which the SOS
response was constitutively derepressed repaired CPDs more rapidly than did wild
type cells, and this rate was not affected by rifampin. Transcription-coupled
repair of CPDs occurred in the absence of SOS induction but was undetectable when
the response was expressed constitutively. These results suggest that damage
inducible synthesis of UvrA and UvrB is necessary for efficient repair of CPDs
and that the levels of these proteins determine the rate of NER of UV
photoproducts. We compare our findings with recent data from eukaryotic systems
and suggest that damage-inducible stress responses are generally critical for
efficient global repair of certain types of genomic damage.
PMID- 9642187
TI - Mutagenesis and expression of amo, which codes for ammonia monooxygenase in
Nitrosomonas europaea.
AB - Nitrosomonas europaea has two copies of the operon encoding ammonia monooxygenase
(AMO). The nucleotide sequences of the two copies of amoA were obtained, and they
were found to differ by one nucleotide. To determine if both copies of amoA were
functional, insertional mutagenesis was performed to inactivate either copy of
amoA alone. A DNA cassette containing the lacZ and kan genes inserted into amoA
was constructed. Mutagenesis was done by using transformation and homologous
recombination to mobilize the cassette into the chromosomal copies of amoA.
Mutations were obtained in both copies of amoA. Either copy of amoA was
sufficient to support growth when the other copy was disrupted. However,
inactivation of one copy of amoA, but not the other, resulted in slower growth.
Measurements of ammonia-dependent O2 consumption, which depends on AMO, confirmed
that the slower-growing mutant had lower activity while the faster-growing mutant
had near wild-type levels of activity. Similarly, as measured by [14C]acetylene
label incorporation, there was less active AMO present in the slower-growing
mutant than in the faster-growing mutant or in the wild type. Northern blot
analysis of transcription likewise showed that the slower-growing mutant had less
full-sized AMO mRNA.
PMID- 9642188
TI - Replication terminator protein-based replication fork-arrest systems in various
Bacillus species.
AB - The replication terminator protein (RTP) of Bacillus subtilis interacts with its
cognate DNA terminators to cause replication fork arrest, thereby ensuring that
the forks approaching one another at the conclusion of a round of replication
meet within a restricted terminus region. A similar situation exists in
Escherichia coli, but it appears that the fork-arrest systems in these two
organisms have evolved independently of one another. In the present work, RTP
homologs in four species closely related to B. subtilis (B. atrophaeus, B.
amyloliquefaciens, B. mojavensis, and B. vallismortis) have been identified and
characterized. An RTP homolog could not be identified in another closely related
species, B. licheniformis. The nucleotide and amino acid changes from B. subtilis
among the four homologs are consistent with the recently established phylogenetic
tree for these species. The GC contents of the rtp genes raise the possibility
that these organisms arose within this branch of the tree by horizontal transfer
into a common ancestor after their divergence from B. licheniformis. Only 5 amino
acid residue positions were changed among the four homologs, despite an up to
17.2% change in the nucleotide sequence, a finding that highlights the importance
of the precise folded structure to the functioning of RTP. The absence of any
significant change in the proposed DNA-binding region of RTP emphasizes the
importance of its high affinity for the DNA terminator in its functioning. By
coincidence, the single change (E30K) found in the B. mojavensis RTP corresponds
exactly to that purposefully introduced by others into B. subtilis RTP to
implicate a crucial role for E30 in the fork-arrest mechanism. The natural
occurrence of this variant is difficult to reconcile with such an implication,
and it was shown directly that RTP.E30K functions normally in fork arrest in B.
subtilis in vivo. Additional DNA terminators were identified in the new RTP
homolog-containing strains, allowing the definition of a Bacillus terminator
consensus and identification of two more terminators in the B. subtilis 168
genome sequence to bring the total to nine.
PMID- 9642189
TI - Enantioselective uptake and degradation of the chiral herbicide dichlorprop [(RS)
2-(2,4-dichlorophenoxy)propanoic acid] by Sphingomonas herbicidovorans MH.
AB - Sphingomonas herbicidovorans MH was able to completely degrade both enantiomers
of the chiral herbicide dichlorprop [(RS)-2-(2,4-dichlorophenoxy)propanoic acid],
with preferential degradation of the (S) enantiomer over the (R) enantiomer.
These results are in agreement with the recently reported enantioselective
degradation of mecoprop [(RS)-2-(4-chloro-2-methylphenoxy)propanoic acid] by this
bacterium (C. Zipper, K. Nickel, W. Angst, and H.-P. E. Kohler, Appl. Environ.
Microbiol. 62:4318-4322, 1996). Uptake of (R)-dichlorprop, (S)-dichlorporp, and
2,4-D (2,4-dichlorophenoxyacetic acid) was inducible. Initial uptake rates of
cells grown on the respective substrate showed substrate saturation kinetics with
apparent affinity constants (Kt) of 108, 93, and 117 microM and maximal
velocities (Vmax) of 19, 10, and 21 nmol min-1 mg of protein-1 for (R)
dichlorprop, (S)-dichlorprop, and 2,4-D, respectively. Transport of (R)
dichlorprop, (S)-dichlorprop, and 2,4-D was completely inhibited by various
uncouplers and by nigericin but was only marginally inhibited by valinomycin and
by the ATPase inhibitor N,N'-dicyclohexylcarbodiimine. Experiments on the
substrate specificity of the putative transport systems revealed that (R)
dichlorprop uptake was inhibited by (R)-mecoprop but not by (S)-mecoprop, (S)
dichlorprop, or 2,4-D. On the other hand, the (S)-dichlorprop transport was
inhibited by (S)-mecoprop but not by (R)-mecoprop, (R)-dichlorprop, or 2,4-D.
These results provide evidence that the first step in the degradation of
dichlorprop, mecoprop, and 2,4-D by S. herbicidovorans is active transport and
that three inducible, proton gradient-driven uptake systems exist: one for (R)
dichlorprop and (R)-mecoprop, another for (S)-dichlorprop and (S)-mecoprop, and a
third for 2,4-D.
PMID- 9642190
TI - Regulation of switching frequency and bias of the bacterial flagellar motor by
CheY and fumarate.
AB - The effect of CheY and fumarate on switching frequency and rotational bias of the
bacterial flagellar motor was analyzed by computer-aided tracking of tethered
Escherichia coli. Plots of cells overexpressing CheY in a gutted background
showed a bell-shaped correlation curve of Switching frequency and bias centering
at about 50% clockwise rotation. Gutted cells (i.e., with cheA to cheZ deleted)
with a low CheY level but a high cytoplasmic fumarate concentration displayed the
same correlation of switching frequency and bias as cells overexpressing CheY at
the wild-type fumarate level. Hence, a high fumarate level can phenotypically
mimic CheY overexpression by simultaneously changing the switching frequency and
the bias. A linear correlation of cytoplasmic fumarate concentration and
clockwise rotation bias was found and predicts exclusively counter-clockwise
rotation without switching when fumarate is absent. This suggests that (i)
fumarate is essential for clockwise rotation in vivo and (ii) any metabolically
induced fluctuation of its cytoplasmic concentration will result in a transient
change in bias and switching probability. A high fumarate level resulted in a
dose-response curve linking bias and cytoplasmic CheY concentration that was
offset but with a slope similar to that for a low fumarate level. It is concluded
that fumarate and CheY act additively presumably at different reaction steps in
the conformational transition of the switch complex from counterclockwise to
clockwise motor rotation.
PMID- 9642191
TI - Sed1p is a major cell wall protein of Saccharomyces cerevisiae in the stationary
phase and is involved in lytic enzyme resistance.
AB - A 260-kDa structural cell wall protein was purified from sodium dodecyl sulfate
treated cell walls of Saccharomyces cerevisiae by incubation with Rarobacter
faecitabidus protease I, which is a yeast-lytic enzyme. Amino acid sequence
analysis revealed that this protein is the product of the SED1 gene. SED1 was
formerly identified as a multicopy suppressor of erd2, which encodes a protein
involved in retrieval of luminal endoplasmic reticulum proteins from the
secretory pathway. Sed1p is very rich in threonine and serine and, like other
structural cell wall proteins, contains a putative signal sequence for the
addition of a glycosylphosphatidylinositol anchor. However, the fact that Sed1p,
unlike other cell wall proteins, has six cysteines and seven putative N
glycosylation sites suggests that Sed1p belongs to a new family of cell wall
proteins. Epitope-tagged Sed1p was detected in a beta-1,3-glucanase extract of
cell walls by immunoblot analysis, suggesting that Sed1p is a glucanase
extractable cell wall protein. The expression of Sed1p mRNa increased in the
stationary phase and was accompanied by an increase in the Sed1p content of cell
walls. Disruption of SED1 had no effect on exponentially growing cells but made
stationary-phase cells sensitive to Zymolyase. These results indicate that Sed1p
is a major structural cell wall protein in stationary-phase cells and is required
for lytic enzyme resistance.
PMID- 9642192
TI - Identification and characterization of two quiescent porin genes, nmpC and ompN,
in Escherichia coli BE.
AB - The genomic DNA of the BE strain of Escherichia coli has been scrutinized to
detect porin genes that have not been identified so far. Southern blot analysis
yielded two DNA segments which proved highly homologous to, yet distinct from,
the ompC, ompF, and phoE porin genes. The two genes were cloned and sequenced.
One of them, designated ompN, encodes a porin which, due to low levels of
expression, has eluded prior identification. The functional properties (single
channel conductance) of the OmpN porin, purified to homogeneity, closely resemble
those of the OmpC porin from E. coli K-12. The second DNA fragment detected
corresponds to the nmpC gene, which, due to an insertion of an IS1 element in its
coding region, is not expressed in E. coli BE.
PMID- 9642193
TI - Identification of a specific chaperone for SptP, a substrate of the centisome 63
type III secretion system of Salmonella typhimurium.
AB - Salmonella typhimurium uses of a type III protein secretion system encoded at
centisome 63 of its chromosome to deliver effector molecule into the host cell.
These proteins stimulate host cell responses such as reorganization of the actin
cytoskeleton and activation of transcription factors. One of these effector
proteins is SptP, a tyrosine phosphatase that causes disruption of the host cell
actin cytoskeleton. A characteristic feature of many substrates of type III
secretion systems is their association with specific cytoplasmic chaperones which
appears to be required for secretion and/or translocation of these proteins into
the host cell. We report here the identification of SicP, a 13-kDa acidic
polypeptide that is encoded immediately upstream of sptP. A loss-of-function
mutation in sicP resulted in drastically reduced levels of SptP but did not
affect sptP expression, indicating that SicP exerts its effect
posttranscriptionally. Pulse-chase experiments demonstrated that the loss of SicP
leads to increased degradation of SptP. In addition, we show that SicP binds to
SptP directly and that the binding site is located between residues 15 and 100 of
the tyrosine phosphatase. Taken together, these results indicate that SicP acts
as a specific chaperone for SptP.
PMID- 9642194
TI - Expression of the bglH gene of Lactobacillus plantarum is controlled by carbon
catabolite repression.
AB - A newly identified bglH gene coding for a phospho-beta-glucosidase of
Lactobacillus plantarum was isolated and expressed in Escherichia coli. The
sequence analysis of the cloned DNA fragment showed an open reading frame
encoding a 480-amino-acid protein with a calculated molecular mass of 53 kDa. The
bglH gene was shown to be expressed on a monocistronic transcriptional unit. Its
transcription was repressed 10-fold in L. plantarum cells grown on glucose
compared to the beta-glucoside salicin as a sole carbon source. A catabolite
responsive element (CRE) spanning from -3 to +11 with respect to the
transcriptional start point was found, and its functionality was assessed by
mutational analysis. In vitro and in vivo DNA binding experiments suggested the
occurrence of a DNA-protein complex at the CRE site, which would mediate glucose
repression of bglH expression.
PMID- 9642195
TI - Genetic recombination in Bacillus subtilis 168: effects of recU and recS
mutations on DNA repair and homologous recombination.
AB - Bacillus subtilis recombination-deficient mutants were constructed by inserting a
selectable marker (cat gene) into the yppB and ypbC coding regions. The yppB:cat
and ypbC:cat null alleles rendered cells sensitive to DNA-damaging agents,
impaired plasmid transformation (25- and 100-fold), and moderately affected
chromosomal transformation when present in an otherwise Rec+ B. subtilis strain.
The yppB gene complemented the defect of the recG40 strain. yppB and ypbC and
their respective null alleles were termed "recU" and "recU1" (recU:cat) and
"recS" and "recS1" (recS:cat), respectively. The recU and recS mutations were
introduced into rec-deficient strains representative of the alpha (recF), beta
(addA5 addB72), gamma (recH342), and epsilon (recG40) epistatic groups. The recU
mutation did not modify the sensitivity of recH cells to DNA-damaging agents, but
it did affect inter- and intramolecular recombination in recH cells. The recS
mutation did not modify the sensitivity of addAB cells to DNA-damaging agents,
and it marginally affected recF, recH, and recU cells. The recS mutation markedly
reduced (about 250-fold) intermolecular recombination in recH cells, and there
were reductions of 10- to 20-fold in recF, addAB, and recU cells. Intramolecular
recombination was blocked in recS recF, recS addAB, and recS recU cells. RecU and
RecS have no functional counterparts in Escherichia coli. Altogether, these data
indicate that the recU and recS proteins are required for DNA repair and
intramolecular recombination and that the recF (alpha epistatic group), addAB
(beta), recH (gamma), recU (epsilon), and recS genes provide overlapping
activities that compensate for the effects of single mutation. We tentatively
placed recS within a new group, termed "zeta".
PMID- 9642196
TI - The V antigen of Yersinia pestis regulates Yop vectorial targeting as well as Yop
secretion through effects on YopB and LcrG.
AB - Yersinia pestis expresses a set of secreted proteins called Yops and the
bifunctional LcrV, which has both regulatory and antihost functions. Yops and
LcrV expression and the activity of the type III mechanism for their secretion
are coordinately regulated by environmental signals such as Ca2+ concentration
and eukaryotic cell contact. In vitro, Yops and LcrV are secreted into the
culture medium in the absence of Ca2+ as part of the low-Ca2+ response (LCR). The
LCR is induced in a tissue culture model by contact with eukaryotic cells that
results in Yop translocation into cells and subsequent cytotoxicity. The
secretion mechanism is believed to indirectly regulate expression of lcrV and yop
operons by controlling the intracellular concentration of a secreted negative
regulator. LcrG, a secretion-regulatory protein, is thought to block secretion of
Yops and LcrV, possibly at the inner face of the inner membrane. A recent model
proposes that when the LCR is induced, the increased expression of LcrV yields an
excess of LcrV relative to LcrG, and this is sufficient for LcrV to bind LcrG and
unblock secretion. To test this LcrG titration model, LcrG and LcrV were
expressed alone or together in a newly constructed lcrG deletion strain, a delta
lcrG2 mutant, of Y. pestis that produces low levels of LcrV and constitutively
expresses and secretes Yops. Overexpression of LcrG in this mutant background was
able to block secretion and depress expression of Yops in the presence of Ca2+
and to dramatically decrease Yop expression and secretion in growth medium
lacking Ca2+. Overexpression of both LcrG and LcrV in the delta lcrG2 strain
restored wild-type levels of Yop expression and Ca2+ control of Yop secretion.
Surprisingly, when HeLa cells were infected with the delta lcrG2 strain, no
cytotoxicity was apparent and translocation of Yops was abolished. This
correlated with an altered distribution of YopB as measured by accessibility to
trypsin. These effects were not due to the absence of LcrG, because they were
alleviated by restoration of LcrV expression and secretion alone. LcrV itself was
found to enter HeLa cells in a nonpolarized manner. These studies supported the
LcrG titration model of LcrV's regulatory effect at the level of Yop secretion
and revealed a further role of LcrV in the deployment of YopB, which in turn is
essential for the vectorial translocation of Yops into eukaryotic cells.
PMID- 9642197
TI - Cloning, sequencing, and phenotypic characterization of the rpoS gene from
Pseudomonas putida KT2440.
AB - A gene homologous to the rpoS gene of Escherichia coli was cloned from a
Pseudomonas putida KT2440 gene bank by complementation of the rpoS-deficient
strain E. coli ZK918. The rpoS gene of P. putida complemented the acid
sensitivity and catalase deficiency of the rpoS mutant of E. coli and stimulated
expression of the RpoS-controlled promoter, bolAp1. The gene was sequenced and
found to be highly similar to the rpoS genes of other gram-negative bacteria.
Like in other gram-negative bacteria, a homolog of the nlpD gene was found
upstream to the rpoS gene. A transcriptional fusion of the promoter of the P.
putida rpoS gene to the luxAB genes from Vibrio harveyi was constructed and used
as an inactivated allele of rpoS for gene replacement of the wild-type copy in
the chromosome of P. putida. The resultant rpoS mutant of P.putida, C1R1, showed
reduced survival of carbon starvation and reduced cross-protection against other
types of stress in cells starved for carbon, in particular after a challenge with
ethanol. Survival in soil amended with m-methylbenzoate was also reduced in the
mutant strain P. putida C1R1. The RpoS protein of P. putida controls the
expression of more than 50 peptides, which are normally expressed in cells after
a short period of carbon starvation.
PMID- 9642198
TI - Clustered genes encoding the methyltransferases of methanogenesis from
monomethylamine.
AB - Coenzyme M (CoM) is methylated during methanogenesis from monomethyamine in a
reaction catalyzed by three proteins. Using monomethylamine, a 52-kDa polypeptide
termed monomethylamine methyltransferase (MMAMT) methylates the corrinoid
cofactor bound to a second polypeptide, monomethylamine corrinoid protein (MMCP).
Methylated MMCP then serves as a substrate for MT2-A, which methylates CoM. The
genes for these proteins are clustered on 6.8 kb of DNA in Methanosarcina barkeri
MS. The gene encoding MMCP (mtmC) is located directly upstream of the gene
encoding MMAMT (mtmB). The gene encoding MT2-A (mtbA) was found 1.1 kb upstream
of mtmC, but no obvious open reading frame was found in the intergenic region
between mtbA and mtmC. A single monocistronic transcript was found for mtbA that
initiated 76 bp from the translational start. Separate transcripts of 2.4 and 4.7
kb were detected, both of which carried mtmCB. The larger transcript also encoded
mtmP, which is homologous to the APC family of cationic amine permeases and may
therefore encode a methylamine permease. A single transcriptional start site was
found 447 bp upstream of the translational start of mtmC. MtmC possesses the
corrinoid binding motif found in corrinoid proteins involved in dimethylsulfide-
and methanol-dependent methanogenesis, as well as in methionine synthase. The
open reading frame of mtmB was interrupted by a single in-frame, midframe, UAG
codon which was also found in mtmB from M. barkeri NIH. A mechanism that
circumvents UAG-directed termination of translation must operate during
expression of mtmB in this methanogen.
PMID- 9642199
TI - Membrane-bound lytic endotransglycosylase in Escherichia coli.
AB - The gene for a novel endotype membrane-bound lytic transglycosylase, emtA, was
mapped at 26.7 min of the E. coli chromosome. EmtA is a lipoprotein with an
apparent molecular mass of 22kDa. Overexpression of the emtA gene did not result
in bacteriolysis in vivo, but the enzyme was shown to hydrolyze glycan strands
isolated from murein by amidase treatment. The formation of tetra- and
hexasaccharides, but no disaccharides, reflects the endospecificity of the
enzyme. The products are characterized by the presence of 1,6-anhydromuramic
acid, indicating a lytic transglycosylase reaction mechanism. EmtA may function
as a formatting enzyme that trims the nascent murein strands produced by the
murein synthesis machinery into proper sizes, or it may be involved in the
formation of tightly controlled minor holes in the murein sacculus to facilitate
the export of bulky compounds across the murein barrier.
PMID- 9642200
TI - The A1A0 ATPase from Methanosarcina mazei: cloning of the 5' end of the aha
operon encoding the membrane domain and expression of the proteolipid in a
membrane-bound form in Escherichia coli.
AB - Three additional ATPase genes, clustered in the order ahaH, ahaI, and ahaK, were
found upstream of the previously characterized genes ahaECFABDG coding for the
archaeal A1A0 ATPase from Methanosarcina mazei. ahaH, the first gene in the
cluster, is preceded by a conserved promoter sequence. Northern blot analysis
revealed that the clusters ahaHIK and ahaECFABDG are transcribed as one message.
AhaH is a hydrophilic polypeptide and is similar to peptides of previously
unassigned function encoded by genes preceding postulated ATPase genes in
Methanobacterium thermoautotrophicum and Methanococcus jannaschii. AhaI has a two
domain structure with a hydrophilic domain of 39 kDa and a hydrophobic domain
with seven predicted transmembrane alpha helices. It is similar to the 100-kDa
polypeptide of V1V0 ATPases and is therefore suggested to participate in proton
transport. AhaK is a hydrophobic polypeptide with two predicted transmembrane
alpha helices and, on the basis of sequence comparisons and immunological
studies, is identified as the proteolipid, a polypeptide which is essential for
proton translocation. However, it is only one-half and one-third the size of the
proteolipids from M. thermoautotrophicum and M. jannaschii, respectively. ahaK is
expressed in Escherichia coli, and it is incorporated into the cytoplasmic
membrane despite the different chemical natures of lipids from archaea and
bacteria. This is the first report on the expression and incorporation into E.
coli lipids of a membrane integral enzyme from a methanogens, which will
facilitate analysis of the structure and function of the membrane domain of the
methanoarchaeal ATPase.
PMID- 9642201
TI - Evolution of cyanobacteria by exchange of genetic material among phyletically
related strains.
AB - The cyanobacterial radiation consists of several lineages of phyletically
(morphologically and genetically) related organisms. Several of these organisms
show a striking resemblance to fossil counterparts. To investigate the molecular
mechanisms responsible for stabilizing or homogenizing cyanobacterial characters,
we compared the evolutionary rates and phylogenetic origins of the small-subunit
rRNA-encoding DNA (16S rDNA), the conserved gene rbcL (encoding D-ribulose 1,5
bisphosphate carboxylase-oxygenase large subunit), and the less conserved gene
rbcX. This survey includes four categories of phyletically related organisms: 16
strains of Microcystis, 6 strains of Tychonema, 10 strains of Planktothrix, and
12 strains of Nostoc. Both rbcL and rbcX can be regarded as neutrally evolving
genes, with 95 to 100% and 50 to 80% synonymous nucleotide substitutions,
respectively. There is generally low sequence divergence within the Microcystis,
Tychonema, and Planktothrix categories both for rbcLX and 16S rDNA. The Nostoc
category, on the other hand, consists of three genetically clustered lineages for
these loci. The 16S rDNA and rbcLX phylogenies are not congruent for strains
within the clustered groups. Furthermore, analysis of the phyletic structure for
rbcLX indicates recombinational events between the informative sites within this
locus. Thus, our results are best explained by a model involving both intergenic
and intragenic recombinations. This evolutionary model explains the DNA sequence
clustering for the modern species as a result of sequence homogenization
(concerted evolution) caused by exchange of genetic material for neutrally
evolving genes. The morphological clustering, on the other hand, is explained by
structural and functional stability of these characters. We also suggest that
exchange of genetic material for neutrally evolving genes may explain the
apparent stability of cyanobacterial morphological characters, perhaps over
billions of years.
PMID- 9642202
TI - Does disparate occurrence of autoregulatory programmed frameshifting in decoding
the release factor 2 gene reflect an ancient origin with loss in independent
lineages?
AB - In Escherichia coli an autoregulatory mechanism of programmed ribosomal
frameshifting governs the level of polypeptide chain release factor 2. From an
analysis of 20 sequences of genes encoding release factor 2, we infer that this
frameshift mechanism was present in a common ancestor of a large group of
bacteria and has subsequently been lost in three independent lineages.
PMID- 9642203
TI - Secretion of elastinolytic enzymes and their propeptides by Pseudomonas
aeruginosa.
AB - Elastase of Pseudomonas aeruginosa is synthesized as a preproenzyme. The signal
sequence is cleaved off during transport across the inner membrane and, in the
periplasm, proelastase is further processed. We demonstrate that the propeptide
and the mature elastase are both secreted but that the propeptide is degraded
extracellularly. In addition, reduction of the extracellular proteolytic activity
led to the accumulation of unprocessed forms of LasA and LasD in the
extracellular medium, which shows that these enzymes are secreted in association
with their propeptides. Furthermore, a hitherto undefined protein with homology
to a Streptomyces griseus aminopeptidase accumulated under these conditions.
PMID- 9642204
TI - tetA(L) mutants of a tetracycline-sensitive strain of Bacillus subtilis with the
polynucleotide phosphorylase gene deleted.
AB - A Bacillus subtilis strain with the polynucleotide phosphorylase gene deleted was
sensitive for growth in the presence of tetracycline. This strain was used to
select for tetracycline-resistant mutants. A point mutation in the tetA(L)
promoter and a spontaneously occurring tetA(L) gene copy number mutant were
characterized.
PMID- 9642205
TI - Identification of the repressor-encoding gene of the Lactobacillus bacteriophage
A2.
AB - The repressor gene of the Lactobacillus phage A2 has the following properties: it
(i) encodes a 224-residue polypeptide with DNA binding and RecA cleavage motifs,
(ii) is expressed in lysogenic cultures, and (iii) confers superinfection
immunity on the host. Adjacent, but divergently transcribed, lies another open
reading frame whose product resembles the lambda Cro protein. In the 161-bp
intergenic segment, putative promoters and operators have been detected.
PMID- 9642206
TI - Characterization of the earliest known Staphylococcus aureus plasmid encoding a
multidrug efflux system.
AB - The staphylococcal qacB-encoding multidrug resistance plasmid pSK156, isolated
from a clinical strain dating from 1951, was characterized. Comparison of the
regions flanking qacB with other qacA- and qacB-encoding plasmids provided
insights into the evolution and dissemination of these multidrug efflux genes and
led to the detection of the earliest known copy of the insertion sequence IS257.
PMID- 9642207
TI - Mutants of Citrobacter freundii that transport and utilize melibiose.
AB - We have isolated mutants of Citrobacter freundii that can grow on melibiose.
Inducible alpha-galactosidase activity and melibiose transport activity were
detected in the mutant cells but not in the wild-type cells. We detected a DNA
region which hybridized with melB (the gene for the melibiose transporter) DNA of
Escherichia coli in the chromosomal DNA of wild-type C. freundii. Protons, but
not sodium ions, were found to be the coupling cations for melibiose (and methyl
beta-D-thiogalactoside) transport in the mutant cells.
PMID- 9642208
TI - The fnr gene of Bacillus licheniformis and the cysteine ligands of the C-terminal
FeS cluster.
AB - In the facultatively anaerobic bacterium Bacillus licheniformis a gene encoding a
protein of the fumarate nitrate reductase family of transcriptional regulators
(Fnr) was isolated. Unlike Fnr proteins from gram-negative bacteria, but like Fnr
from Bacillus subtilis, the protein contained a C-terminal cluster of cysteine
residues. Unlike in Fnr from B. subtilis, this cluster (Cys226-X2-Cys229-X4
Cys234) is composed of only three Cys residues, which are supposed to serve
together with an internal residue (Cys71) as the ligands for an FeS center.
Transfer of the B. licheniformis gene to an fnr mutant of B. subtilis
complemented the ability for synthesis of nitrate reductase during anaerobic
growth.
PMID- 9642210
TI - KtrAB, a new type of bacterial K(+)-uptake system from Vibrio alginolyticus.
AB - Vibrio alginolyticus contained two adjacent genes, ktrA and ktrB, which encode a
new type of bacterial K(+)-uptake system. KtrA and KtrB are peripheral and
integral membrane proteins, respectively. Six of the nine sequenced bacterial
genomes contain homologs to both ktrA and ktrB, suggesting that KtrAB is
widespread.
PMID- 9642209
TI - Aberrant cell division and random FtsZ ring positioning in Escherichia coli cpxA*
mutants.
AB - In Escherichia coli, certain mutations in the cpxA gene (encoding a sensor kinase
of a two-component signal transduction system) randomize the location of FtsZ
ring assembly and dramatically affect cell division. However, deletion of the
cpxRA operon, encoding the sensor kinase and its cognate regulator CpxR, has no
effect on division site biogenesis. It appears that certain mutant sensor kinases
(CpxA*) either exhibit hyperactivity on CpxR or extend their signalling activity
to one or more noncognate response regulators involved in cell division.
PMID- 9642211
TI - Mechanism of action of human P-glycoprotein ATPase activity. Photochemical
cleavage during a catalytic transition state using orthovanadate reveals cross
talk between the two ATP sites.
AB - Human P-glycoprotein (P-gp), an ATP-dependent efflux pump responsible for cross
resistance of human cancers to a variety of lipophilic compounds, is composed of
two homologous halves, each containing six transmembrane domains and an ATP
binding/utilization domain. To determine whether each site can hydrolyze ATP
simultaneously, we used an orthovanadate (Vi)-induced ADP-trapping technique (P
gp.MgADP.Vi). In analogy with other ATPases, a photochemical peptide bond
cleavage reaction occurs within the Walker A nucleotide binding domain consensus
sequence (GX4GK(T/S)) when the molecule is trapped with Vi in an inhibited
catalytic transition state (P-gp.MgADP.Vi) and incubated in the presence of
ultraviolet light. Upon reconstitution into proteoliposomes, histidine-tagged
purified P-gp from baculovirus-infected insect cells had drug-stimulated ATPase
activity. Reconstituted P-gp was incubated with either ATP or 8-azido-ATP in the
presence or absence of Vi under ultraviolet (365 nm) light on ice for 60 min. The
resultant products were separated by SDS-polyacrylamide gel electrophoresis and
subjected to immunoblotting with seven different human P-gp-specific antibodies
covering the entire length of the molecule. Little to no degradation of P-gp was
observed in the absence of Vi. In the presence of Vi, products of approximately
28, 47, 94, and 110 kDa were obtained, consistent with predicted molecular
weights from cleavage at either of the ATP sites but not both sites. An
additional Vi-dependent cleavage site was detected at or near the trypsin site in
the linker region of P-gp. These results suggest that both the amino- and
carboxyl-terminal ATP sites can hydrolyze ATP. However, there is no evidence that
ATP can be hydrolyzed simultaneously by both sites.
PMID- 9642212
TI - A role for phospholipase D (Pld1p) in growth, secretion, and regulation of
membrane lipid synthesis in yeast.
AB - The SEC14 gene encodes a phosphatidylinositol/phosphatidylcholine transfer
protein essential for secretion and growth in yeast (1). Mutations (cki1, cct1,
and cpt1) in the CDP-choline pathway for phosphatidylcholine synthesis suppress
the sec14 growth defect (2), permitting sec14(ts) cki1, sec14(ts) cct1, and
sec14(ts) cpt1 strains to grow at the sec14(ts) restrictive temperature.
Previously, we reported that these double mutant strains also excrete the
phospholipid metabolites, choline and inositol (3). We now report that these
choline and inositol excretion phenotypes are eliminated when the SPO14 (PLD1)
gene encoding phospholipase D1 is deleted. In contrast to sec14(ts) cki1 strains,
sec14(ts) cki1 pld1 strains are not viable at the sec14(ts) restrictive
temperature and exhibit a pattern of invertase secretion comparable with
sec14(ts) strains. Thus, the PLD1 gene product appears to play an essential role
in the suppression of the sec14(ts) defect by CDP-choline pathway mutations,
indicating a role for phospholipase D1 in growth and secretion. Furthermore,
sec14(ts) strains exhibit elevated Ca2+-independent, phophatidylinositol 4,5
bisphosphate-stimulated phospholipase D activity. We also propose that
phospholipase D1-mediated phosphatidylcholine turnover generates a signal that
activates transcription of INO1, the structural gene for inositol 1-phosphate
synthase.
PMID- 9642213
TI - High-affinity binding of epidermal growth factor (EGF) to EGF receptor is
disrupted by overexpression of mutant dynamin (K44A).
AB - Activation of the epidermal growth factor receptor (EGFR) kinase was analyzed in
cells conditionally defective for clathrin-dependent endocytosis by
overexpression of mutant dynamin (K44A). EGF-induced autophosphorylation of the
EGFR on ice was strongly reduced in cells overexpressing mutant dynamin, and
consistently, binding analyses showed that high-affinity EGFRs were lost. In the
absence of mutant dynamin the cells displayed both high- and low-affinity EGFR.
At 4 degreesC EGF-EGFR localized mainly outside coated pits regardless of
expression of mutant dynamin. However, also low-affinity EGFR efficiently moved
to coated pits upon incubating cells at 37 degreesC. Thus, expression of mutant
dynamin disrupts high-affinity binding of EGF, but not ligand-induced recruitment
of EGFR to clathrin-coated pits.
PMID- 9642214
TI - A common requirement for the catalytic activity and both SH2 domains of SHP-2 in
mitogen-activated protein (MAP) kinase activation by the ErbB family of
receptors. A specific role for SHP-2 in map, but not c-Jun amino-terminal kinase
activation.
AB - The ErbB family of receptors, which include the epidermal growth factor receptor
(EGFR), ErbB2, ErbB3, and ErbB4 mediate the actions of a family of bioactive
polypeptides. EGF signals through EGFR, whereas heregulin (HRG) signaling is
initiated through binding to either ErbB3 or ErbB4. In this report we studied the
role of protein-tyrosine phosphatase SHP-2 in ErbB-mediated activation of mitogen
activated protein kinase (MAPK) by overexpressing SHP-2 mutants in COS-7 cells.
We demonstrate that enzymatic activity and both NH2- and COOH-terminal SH2
domains of SHP-2 are required for EGF-induced MAPK activation, but not for c-Jun
amino-terminal kinase stimulation or MAPK activation which occurred in response
to myristoylated son of sevenless, activated Ras, or phorbol ester. Dominant
negative forms of SHP-2 had no effect on EGF-stimulated interaction of GRB2 with
EGFR or SHC, nor did they influence phosphorylation of SHC and SHC/EGFR
association. The same mutant SHP-2 structures that inhibited EGF-mediated
stimulation of MAPK also blocked HRG alpha/beta-induced MAPK activation. EGF or
HRG beta caused SHP-2 SH2 domains to engage multiple phosphotyrosine proteins,
and mutation of either domain disrupted these associations. These results
demonstrate that SHP-2 performs a common and essential function(s) in ligand
stimulated MAPK activation by the ErbB family of receptors.
PMID- 9642215
TI - Abrogation of mitochondrial cytochrome c release and caspase-3 activation in
acquired multidrug resistance.
AB - Acquired multidrug resistance to anti-cancer agents has been associated with
overexpression of the P-glycoprotein and other members of the ATP-binding
cassette superfamily. The present studies demonstrate that SCC-25 cells selected
for resistance to the alkylating agent cisplatin (CDDP) overexpress the anti
apoptotic Bcl-xL protein. In contrast to parental cells, the SCC-25/CDDP
resistant variant failed to exhibit activation of caspase-3, cleavage of protein
kinase C delta, and other characteristics of apoptosis in response to CDDP.
Similar results were obtained when SCC-25/CDDP cells were exposed to the
structurally and functionally unrelated antimetabolite 1-beta-D-arabinofuranosyl
cytosine (ara-C). Other cells selected for resistance to doxorubicin or
vincristine also exhibited overexpression of Bcl-xL and failed to respond to CDDP
and ara-C with activation of caspase-3. The results further demonstrate that
multidrug-resistant cells exhibit a block in the release of mitochondrial
cytochrome c into the cytosol and that this effect is dependent on overexpression
of Bcl-xL. The demonstration that lysates from the resistant cells respond to the
addition of cytochrome c with activation of caspase-3 confirms that the block in
apoptosis is because of inhibition of mitochondrial cytochrome c release. These
findings demonstrate that cells respond to diverse classes of anti-cancer drugs
with overexpression of Bcl-xL and that this response represents another mechanism
of acquired multidrug resistance.
PMID- 9642216
TI - Steroid receptor coactivator-1 coactivates activating protein-1-mediated
transactivations through interaction with the c-Jun and c-Fos subunits.
AB - Steroid receptor coactivator-1 (SRC-1) specifically bound to the transcription
factor AP-1 subunits c-Jun and c-Fos, as demonstrated by the yeast two-hybrid
tests and glutathione S-transferase pull down assays. The c-Jun and c-Fos binding
sites were localized to the C-terminal subregion of SRC-1 (amino acids 1101-1441)
that encompasses the previously described histone acetyltransferase and receptor
binding domains. In mammalian cells, SRC-1, similar to the previous results with
CBP-p300 (Arias, J., Alberts, A. S., Brindle, P., Claret, F. X., Smeal, T.,
Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-229; Bannister,
A. J., and Kouzarides, T. (1995) EMBO J. 14, 4758-4762), potentiated the AP-1
mediated transactivations in a dose-dependent manner and derepressed the mutual
inhibitions between nuclear receptors and AP-1. Furthermore, coexpression of p300
further enhanced this SRC-1-potentiated level of transactivations. Thus, we
concluded that at least two distinct coactivator molecules may cooperate to
regulate AP-1-dependent transactivations and mediate transrepression between AP-1
and nuclear receptors in vivo.
PMID- 9642217
TI - Transformation activity of Cdc42 requires a region unique to Rho-related
proteins.
AB - The Rho subfamily GTP-binding protein Cdc42 mediates actin cytoskeletal
rearrangements and cell cycle progression and is essential for Ras
transformation. Expression of a Cdc42 mutant (Cdc42(F28L)) that undergoes
spontaneous activation (guanine nucleotide exchange) results in transformation of
NIH3T3 fibroblasts. In this report, we show that deletion of residues 120-139
from Cdc42(F28L), which comprise an insert region unique to Rho subfamily
proteins but is missing in other GTP-binding proteins, yields a Cdc42 molecule
that still undergoes spontaneous GTP-GDP exchange and stimulates both actin
cytoskeletal changes and the activation of the cellular targets p21-activated
kinase and the c-Jun kinase (JNK1). However, this Cdc42 mutant is unable to
transform cells. These findings indicate that the Rho subfamily insert region is
dispensable for many of the known signaling pathways initiated by activated Cdc42
but is essential for its regulation of cell growth.
PMID- 9642218
TI - Nerve growth factor is mitogenic for cancerous but not normal human breast
epithelial cells.
AB - We show here that nerve growth factor (NGF), the archetypal neurotrophic factor,
is able to stimulate the proliferation of breast cancer cells (MCF-7 and MDA-MB
231 cell lines), although it is unable to stimulate growth of normal breast
epithelial cells (NBEC). This stimulation induced cells in the G0 phase to
reenter the cell cycle, as well as shortening cell cycle duration. Immunoblotting
experiments revealed that both the two cancer cell lines and the NBEC express
high affinity (p140(trk)) and low affinity (p75) NGF receptors. Inhibition of the
NGF growth-promoting effect by the drugs K-252a and PD98059 indicated that
activation of Trk-tyrosine kinase activity and the mitogen-activated protein
kinase cascade are necessary to obtain the mitogenic effect. Activation of
mitogen-activated protein kinase can be detected in breast cancer cells after 10
min of NGF stimulation, whereas no change was detected in NBEC. These results
demonstrate that NGF is a mitogenic factor for human breast cancer cells and that
it might constitute a new regulator of breast tumor growth.
PMID- 9642219
TI - Regulation of the neutrophil respiratory burst oxidase. Identification of an
activation domain in p67(phox).
AB - Superoxide generation by the neutrophil respiratory burst oxidase (NADPH oxidase)
can be reconstituted in a cell-free system using flavocytochrome b558 and the
cytosolic proteins p47(phox), p67(phox), and Rac. p47(phox) functions as an
adaptor protein; it increases the affinity of p67(phox) and Rac in the NADPH
oxidase complex, but is not essential when high concentrations of these proteins
are used (Freeman, J. L., and Lambeth, J. D. (1996) J. Biol. Chem. 271, 22578
22582), implying that p67(phox) and/or Rac directly regulates enzyme activity.
Herein, we describe an activation domain in p67(phox) that is essential for NADPH
oxidase activity. A series of C-terminal truncation mutants of p67(phox) showed
that residues 211 to the C terminus (residue 526) are not needed for cell-free
activity. However, shorter truncations were inactive, pointing to an activation
domain within the region spanning residues 199-210. p67(phox) mutated at single
amino acid residues within this region showed diminished activity, and p67(phox)
V204A was completely inactive. The effects of mutations on activity were
independent of p47(phox), and mutations did not affect the binding of p67(phox)
to Rac. In the presence of wild-type p67(phox), the V204A mutant was a potent
inhibitor of superoxide generation, and inhibition was partially reversed by high
concentrations of p67(phox), but not by p47(phox) or Rac. The V204A mutant
competed with native p67(phox) for translocation to neutrophil plasma membrane,
indicating that p67(phox) V204A assembles to form an inactive complex. The data
imply a direct activation of flavocytochrome b558 by an activation domain in
p67(phox).
PMID- 9642220
TI - Odorants selectively activate distinct G protein subtypes in olfactory cilia.
AB - Chemoelectrical signal transduction in olfactory neurons appears to involve
intracellular reaction cascades mediated by heterotrimeric GTP-binding proteins.
In this study attempts were made to identify the G protein subtype(s) in
olfactory cilia that are activated by the primary (odorant) signal. Antibodies
directed against the alpha subunits of distinct G protein subtypes interfered
specifically with second messenger reponses elicited by defined subsets of
odorants; odor-induced cAMP-formation was attenuated by Galphas antibodies,
whereas Galphao antibodies blocked odor-induced inositol 1,4, 5-trisphosphate
(IP3) formation. Activation-dependent photolabeling of Galpha subunits with
[alpha-32P]GTP azidoanilide followed by immunoprecipitation using subtype
specific antibodies enabled identification of particular individual G protein
subtypes that were activated upon stimulation of isolated olfactory cilia by
chemically distinct odorants. For example odorants that elicited a cAMP response
resulted in labeling of a Galphas-like protein, whereas odorants that elicited an
IP3 response led to the labeling of a Galphao-like protein. Since odorant-induced
IP3 formation was also blocked by Gbeta antibodies, activation of olfactory
phospholipase C might be mediated by betagamma subunits of a Go-like G protein.
These results indicate that different subsets of odorants selectively trigger
distinct reaction cascades and provide evidence for dual transduction pathways in
olfactory signaling.
PMID- 9642221
TI - A novel metal-activated pyridoxal enzyme with a unique primary structure, low
specificity D-threonine aldolase from Arthrobacter sp. Strain DK-38. Molecular
cloning and cofactor characterization.
AB - The gene encoding low specificity D-threonine aldolase, catalyzing the
interconversion of D-threonine/D-allo-threonine and glycine plus acetaldehyde,
was cloned from the chromosomal DNA of Arthrobacter sp. strain DK-38. The gene
contains an open reading frame consisting of 1,140 nucleotides corresponding to
379 amino acid residues. The enzyme was overproduced in recombinant Escherichia
coli cells and purified to homogeneity by ammonium sulfate fractionation and
three-column chromatography steps. The recombinant aldolase was identified as a
pyridoxal enzyme with the capacity of binding 1 mol of pyridoxal 5'-phosphate per
mol of subunit, and Lys59 of the enzyme was determined to be the cofactor binding
site by chemical modification with NaBH4. In addition, Mn2+ ion was demonstrated
to be an activator of the enzyme, although the purified enzyme contained no
detectable metal ions. Equilibrium dialysis and atomic absorption studies
revealed that the recombinant enzyme could bind 1 mol of Mn2+ ion per mol of
subunit. Remarkably, the predicted amino acid sequence of the enzyme showed no
significant similarity to those of the currently known pyridoxal 5'-phosphate
dependent enzymes, indicating that low specificity D-threonine aldolase is a new
pyridoxal enzyme with a unique primary structure. Taken together, low specificity
D-threonine aldolase from Arthrobacter sp. strain DK-38, with a unique primary
structure, is a novel metal-activated pyridoxal enzyme.
PMID- 9642222
TI - The Lutheran blood group glycoproteins, the erythroid receptors for laminin, are
adhesion molecules.
AB - The Lutheran antigens are recently characterized glycoproteins in which the
extracellular region contains five immunoglobulin like domains, suggesting some
recognition function. A recent abstract suggests that the Lutheran glycoproteins
(Lu gps) act as erythrocyte receptors for soluble laminin (Udani, M., Jefferson,
S., Daymont, C., Zen, Q., and Telen, M. J. (1996) Blood 88, Suppl. 1, 6
(abstr.)). In the present report, we provided the definitive proof of the laminin
receptor function of the Lu gps by demonstrating that stably transfected cells
(murine L929 and human K562 cell lines) expressing the Lu gps bound laminin in
solution and acquired adhesive properties to laminin-coated plastic dishes but
not to fibronectin, vitronectin, transferrin, fibrinogen, or fibrin. Furthermore,
expression of either the long-tail (85 kDa) or the short-tail (78 kDa) Lu gps,
which differ by the presence or the absence of the last 40 amino acids of the
cytoplasmic domain, respectively, conferred to transfected cells the same laminin
binding capacity. We also confirmed by flow cytometry analysis that the level of
laminin binding to red cells is correlated with the level of Lu antigen
expression. Indeed, Lunull cells did not bind to laminin, whereas sickle cells
from most patients homozygous for hemoglobin S overexpressed Lu antigens and
exhibited an increased binding to laminin, as compared with normal red cells.
Laminin binding to normal and sickle red cells as well as to Lu transfected cells
was totally inhibited by a soluble Lu-Fc chimeric fragment containing the
extracellular domain of the Lu gps. During in vitro erythropoiesis performed by
two-phase liquid cultures of human peripheral blood, the appearance of Lu
antigens in late erythroid differentiation was concomitant with the laminin
binding capacity of the cultured erythroblasts. Altogether, our results
demonstrated that long-tail and short-tail Lu gps are adhesion molecules that
bind equally well laminin and strongly suggested that these glycoproteins are the
unique receptors for laminin in normal and sickle mature red cells as well as in
erythroid progenitors.
PMID- 9642223
TI - Mitochondrial creatine kinase is a prime target of peroxynitrite-induced
modification and inactivation.
AB - The reaction of peroxynitrite (PN) with sarcomeric mitochondrial creatine kinase
(Mib-CK; EC 2.7.3.2) was observed at different stages of complexity (i) with
purified Mi-CK, (ii) with enzyme bound on isolated mitoplasts, and (iii) within
intact respiring mitochondria. Creatine-stimulated respiration was abolished by
PN concentrations likely to be physiological and far before the respiratory chain
itself was affected, thus demonstrating that Mi-CK is a prime target for
inactivation by PN in intact mitochondria. The inactivation by PN of Mi-CK was
reversed by 22% with 2-mercaptoethanol. More remarkable protective effects were
noticed with the full set of CK substrates, e.g. 30 and 50% protection with MgATP
plus creatine and MgADP plus phosphocreatine, respectively, but not with each
substrate alone. These data indicate an involvement of the active-site Cys-278
residue of Mi-CK in this process. Furthermore, changes in endogenous tryptophan
fluorescence intensity and spectral changes after reaction of Mi-CK with PN
suggest additional modifications of Trp and Tyr residues. PN-inactivated Mi-CK
can no longer be efficiently converted into dimers by incubation with reagents
inducing a transition state analog complex at the active site. Thus, obviously,
upon reaction of octameric Mi-CK with PN, the octamer-dimer equilibrium of Mi-CK
is also affected. The consequences for cellular energy homeostasis and calcium
handling are discussed.
PMID- 9642224
TI - Differential regulation of discrete apoptotic pathways by Ras.
AB - The products of the ras genes are known to regulate cell proliferation and
differentiation; recently, they have been found to play a role in apoptosis. The
expression of oncogenic p21(ras) in a number of cell types, including Jurkat (a
human T lymphoblastoid cell line) and murine fibroblasts, makes the cells
susceptible to apoptosis following suppression of protein kinase C (PKC) activity
(PKC/Ras-mediated apoptosis). Engagement of Fas antigen, a potent effector of
apoptosis, activates cellular p21(ras), which may be required for completion of
the cell death program. To further investigate the role of p21(ras) in the
regulation of apoptosis, the cellular mechanisms employed in these two apoptotic
processes in which Ras activity is involved (PKC/Ras-related and Fas-triggered
apoptosis), was explored. Increasing p21(ras) activity by expressing v-ras or by
treatment with an antisense oligonucleotide to the GTPase-activating protein was
found to accelerate the Fas-mediated apoptotic process in Jurkat and mouse LF
cells. PKC/Ras-related apoptosis was associated with, and required, cell cycle
progression, accompanied by the expression of the G1/S cyclins. In contrast, Fas
engagement, although inducing a vigorous and PKC-independent activation of
endogenous p21(ras), did not alter cell cycle progression, nor did it require
such progression for apoptosis. Both the protein synthesis inhibitor
cycloheximide and cyclin E antisense oligonucleotides partially abolished PKC/Ras
mediated apoptosis but had only a moderate effect on Fas-induced apoptosis. In
contrast, the CED-3/interleukin-1beta-converting enzyme (ICE) protease inhibitor
Z-VADfmk efficiently suppressed Fas-induced apoptosis and only marginally
inhibited PKC/Ras-mediated apoptosis. Induction of both pathways resulted in
activation of the Jun NH2-terminal kinase/JUN signaling system. These results
suggest that different cell death programs, such as PKC/Ras-mediated and Fas
mediated apoptosis, may be interconnected via p21(ras) and perhaps Jun NH2
terminal kinase/JUN. In response to various death stimuli, p21(ras) may act as a
common intermediate regulator in the transduction of apoptotic signals.
PMID- 9642225
TI - Expression of putative fatty acid transporter genes are regulated by peroxisome
proliferator-activated receptor alpha and gamma activators in a tissue- and
inducer-specific manner.
AB - Regulation of gene expression of three putative long-chain fatty acid transport
proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase
(mAspAT), and fatty acid transport protein (FATP), by drugs that activate
peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied
using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver
and intestine of normal mice and in hepatoma cells to various extents only by
PPARalpha-activating drugs. FATP mRNA was similarly induced in liver, but to a
lesser extent in intestine. The induction time course in the liver was slower for
FAT and FATP mRNA than that of an mRNA encoding a peroxisomal enzyme. An
obligatory role of PPARalpha in hepatic FAT and FATP induction was demonstrated,
since an increase in these mRNAs was not observed in PPARalpha-null mice. Levels
of mAspAT mRNA were higher in liver and intestine of mice treated with peroxisome
proliferators, while levels in hepatoma cells were similar regardless of
treatment. In white adipose tissue of KKAy obese mice, thiazolidinedione
PPARgamma activators (pioglitazone and troglitazone) induced FAT and FATP more
efficiently than the PPARalpha activator, clofibrate. This effect was absent in
brown adipose tissue. Under the same conditions, levels of mAspAT mRNA did not
change significantly in these tissues. In conclusion, tissue-specific expression
of FAT and FATP genes involves both PPARalpha and -gamma. Our data suggest that
among the three putative long-chain fatty acid transporters, FAT and FATP appear
to have physiological roles. Thus, peroxisome proliferators not only influence
the metabolism of intracellular fatty acids but also cellular uptake, which is
likely to be an important regulatory step in lipid homeostasis.
PMID- 9642226
TI - Bcl-2 transcription from the proximal P2 promoter is activated in neuronal cells
by the Brn-3a POU family transcription factor.
AB - The BCL-2 protein is able to protect neuronal and other cell types from apoptotic
programmed cell death and plays a key role in regulating the rate of apoptosis
during development of the nervous system. We have previously demonstrated that
the Brn-3a POU domain transcription factor protects sensory neurons from
apoptotic programmed cell death induced by nerve growth factor withdrawal. We
report here that Bcl-2 transcription is predominantly initiated from the Bcl-2 P2
promoter in both the ND7 neuronal cell line and primary dorsal root ganglion
neurons, in contrast to the predominant use of the Bcl-2 P1 promoter in other
cell types. Moreover, Bcl-2 transcription initiated from the P2 region increases
in ND7 cells stably overexpressing Brn-3a, resulting in enhanced BCL-2 protein
levels. Similarly, the Bcl-2 P2 promoter is directly activated by Brn-3a in co
transfection assays in both ND7 cells and dorsal root ganglion neurons. Analysis
of the Bcl-2 regulatory sequence revealed a binding site for Brn-3a that is
required for maximal activation by Brn-3a both in transfected cells and during
differentiation of ND7 cells. Together these data identify Brn-3a as the first
transcription factor regulating Bcl-2 activity specifically in neuronal cells and
indicate that the anti-apoptotic effect of Brn-3a is likely to be mediated, at
least in part, via the up-regulation of Bcl-2 expression.
PMID- 9642227
TI - Osteoadherin, a cell-binding keratan sulfate proteoglycan in bone, belongs to the
family of leucine-rich repeat proteins of the extracellular matrix.
AB - Osteoadherin is a recently described bone proteoglycan containing keratan
sulfate. It promotes integrin (alphav beta3)-mediated cell binding (Wendel, M.,
Sommarin, Y., and Heinegard, D. (1998) J. Cell Biol. 141, 839-847). The primary
structure of bovine osteoadherin has now been determined by nucleotide sequencing
of a cDNA clone from a primary bovine osteoblast expression library. The entire
translated primary sequence corresponds to a 49,116-Da protein with a calculated
isoelectric point for the mature protein of 5.2. The dominating feature is a
central region consisting of 11 B-type, leucine-rich repeats ranging in length
from 20 to 30 residues. The full, primary sequence contains four putative sites
for tyrosine sulfation, three of which are at the N-terminal end of the molecule.
There are six potential sites for N-linked glycosylation present. Osteoadherin
shows highest sequence identity, 42%, to bovine keratocan and 37-38% identity to
bovine fibromodulin, lumican, and human PRELP. Unique to osteoadherin is the
presence of a large and very acidic C-terminal domain. The distribution of
cysteine residues resembles that of other leucine-rich repeat proteins except for
two centrally located cysteines. Northern blot analysis of RNA samples from
various bovine tissues showed a 4.5-kilobase pair message for osteoadherin to be
expressed in bone only. Osteoadherin mRNA was detected by in situ hybridization
in mature osteoblasts located superficially on trabecular bone.
PMID- 9642228
TI - Production of adrenomedullin in macrophage cell line and peritoneal macrophage.
AB - We demonstrate that adrenomedullin (AM) is produced and secreted from cultured
murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal
macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was
chromatographically identified to be native AM. To elucidate the regulation
mechanism of AM production in macrophage, we examined the effects of various
substances inducing differentiation or activation of monocyte/macrophage. Phorbol
ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma
(IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as
well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7
cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic
effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma
completely suppressed AM production in RAW 264.7 cells stimulated with LPS.
Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta
dose-dependently suppressed AM production in RAW 264.7 cells. AM production was
also investigated in mouse peritoneal macrophage. Primary mouse macrophage
secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production
was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion
of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM
suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with
LPS. Thus, macrophage should be recognized as one of the major sources of AM
circulating in the blood. Especially in cases of sepsis and inflammation, AM
production in macrophage is augmented, and the secreted AM is deduced to function
as a modulator of cytokine production.
PMID- 9642229
TI - Transforming potential of Dbl family proteins correlates with transcription from
the cyclin D1 promoter but not with activation of Jun NH2-terminal kinase,
p38/Mpk2, serum response factor, or c-Jun.
AB - The dbl family of oncogenes encodes a large, structurally related, family of
growth-regulatory molecules that possess guanine nucleotide exchange factor
activity for specific members of the Rho family of Ras-related GTPases. We have
evaluated matched sets of weakly and strongly transforming versions of five Dbl
family proteins (Lfc, Lsc, Ect2, Dbl, and Dbs) to determine their ability to
stimulate signaling pathways that are activated by Rho family proteins. We found
that the transforming potential of this panel did not correlate directly with
their ability to activate Jun NH2-terminal kinase, p38/Mpk2, serum response
factor, or c-Jun. In contrast, transient stimulation of transcription from the
cyclin D1 promoter provided a strong correlation with transforming potential, and
we found constitutive up-regulation of cyclin D1 protein in Dbl family protein
transformed cells. In addition, we observed that at least two Dbl family members
(Lfc and Ect2) induced changes in the actin cytoskeleton and exhibited nuclear
signaling profiles that are consistent with a broader range of in vivo substrate
utilization than is predicted from their in vitro exchange specificities. In
summary, although Dbl family proteins exhibit signaling profiles that are
consistent with their in vivo activation of Rho proteins, stimulation of cyclin
D1 transcription is the only activity that correlates with transforming
potential, thus suggesting that deregulated cell cycle progression may be
important for Dbl family protein transformation.
PMID- 9642230
TI - Membrane fusion is induced by a distinct peptide sequence of the sea urchin
fertilization protein bindin.
AB - Fertilization in the sea urchin is mediated by the membrane-associated acrosomal
protein bindin, which plays a key role in the adhesion and fusion between sperm
and egg. We have investigated the structure/function relationship of an 18-amino
acid peptide fragment "B18," which represents the minimal membrane binding motif
of the protein and resembles a putative fusion peptide. The peptide was found to
mimic the behavior of its parent protein bindin with respect to (a) its high
affinity for lipid bilayers, (b) the ability to aggregate and fuse vesicles, (c)
the binding of Zn2+ by a histidine-rich motif, (d) the tendency to self-assemble,
and (e), as indicated earlier, the adhesion to cell surface polysaccharides.
Fluorescence and light scattering assays were used here to monitor peptide
induced lipid mixing, leakage, and aggregation of large unilamellar
sphingomyelin/cholesterol vesicles. For these activities, B18 requires the
presence of Zn2+ ions, with which it forms oligomeric complexes and assumes a
partially alpha-helical conformation, as observed by circular dichroism. We
conclude that aggregation and fusion involves a "trans-complex" between peptides
on apposing vesicles that are connected by Zn2+ bridges.
PMID- 9642231
TI - Common in vitro substrate specificity and differential Src homology 2 domain
accessibility displayed by two members of the Src family of protein-tyrosine
kinases, c-Src and Hck.
AB - Hck and Src are members of the Src family of protein- tyrosine kinases that carry
out distinct and overlapping functions in vivo (Lowell, C. A., Niwa, M., Soriano,
P., and Varmus, H. E. (1996) Blood 87, 1780-1792). In an attempt to understand
how Hck and Src can function both independently and in concert, we have compared
1) their in vitro substrate specificity and 2) the accessibility of their Src
homology 2 (SH2) domain. Using several synthetic peptides, we have demonstrated
that Hck and Src recognize similar structural features in the substrate peptides,
suggesting that both kinases have the intrinsic ability to carry out overlapping
cellular functions by phosphorylating similar cellular proteins in vivo. Using a
phosphotyrosine-containing peptide that has previously been shown to bind the SH2
domain of Src family kinases with high affinity, we found that although Src could
bind to the phosphopeptide, Hck showed no interaction. The inability of Hck to
bind the phosphopeptide was not a result of a stable intramolecular interaction
between its SH2 domain and C-terminal regulatory phosphotyrosine residue (Tyr
520), as most Hck molecules in the purified Hck preparation were not tyrosine
phosphorylated. In contrast to intact Hck, a recombinant truncation analog of Hck
was able to bind the phosphopeptide with an affinity similar to that of the Src
SH2 domain, suggesting that conformational constraints are imposed on intact Hck
that limit accessibility of its SH2 domain to the phosphopeptide. Furthermore,
the difference in SH2 domain accessibility is a potential mechanism that enables
Src and Hck to perform their respective unique functions by 1) targeting them to
different subcellular compartments, whereupon they phosphorylate different
cellular proteins, and/or 2) facilitating direct binding to their cellular
substrates.
PMID- 9642232
TI - Altered properties of the branched chain amino acid-preferring activity
contribute to increased cleavages after branched chain residues by the
"immunoproteasome".
AB - The multicatalytic proteinase complex (MPC, proteasome) is assembled from 14
nonidentical protein subunits. It expresses five distinct proteolytic activities,
including a chymotrypsin-like activity, cleaving after hydrophobic residues, and
a branched chain amino acid-preferring component (BrAAP), cleaving preferentially
after branched chain residues. Exposure of cells to interferons leads to
replacement of the X, Y, and Z subunits by the LMP2, LMP7, and MECL1 subunits.
This "immunoproteasome" is critical to processing of certain antigens. The
enzymatic basis for enhanced antigen processing has not been determined. To gain
insight into this question, we examined sites and relative rates of cleavage of
bonds in denatured, reduced, carboxyamidomethylated lysozyme, a 129-amino acid
protein, by MPC from bovine spleen, in which the X, Y, and Z subunits are
replaced by LMP2, LMP7, and MECL1. We compared cleavages to those catalyzed by
MPC from bovine pituitary, which contains only the X, Y, and Z subunits. We found
marked increases in the rates and number of cleavages after branched chain
residues in reduced, carboxyamidomethylated lysozyme by the spleen MPC. This was
largely due to accelerated cleavages of bonds after a Phi-X-Br motif, where Phi
is a hydrophobic residue, X is a small neutral or polar residue, and Br is a
branched chain residue. Inhibitors with these structural properties were
selective and potent inhibitors of the BrAAP activity of the spleen MPC. The
above findings indicate that alterations in activity and substrate specificity of
the BrAAP activity are important factors underlying the altered cleavages after
hydrophobic residues associated with incorporation of interferon-inducible
subunits. The potential relevance of the findings to antigen processing functions
of MPC is discussed.
PMID- 9642233
TI - Purification and characterization of a novel peptidase (IImes) from mesquite
(Prosopis velutina) pollen.
AB - Although the mesquite plant (Prosopis velutina) is not as widely distributed as
some other allergenic species, its pollen can induce serious pollinosis in areas
where it is localized. We previously isolated and characterized a peptidase from
mesquite pollen with trypsin-like specificity (peptidase Imes) (Matheson, N.,
Schmidt, J., and Travis, J. (1995) Am. J. Respir. Cell Mol. Biol. 12, 441-448).
Now we have characterized a second enzyme with specificity for hydrophobic
residues (mesquite pollen peptidase IImes). This enzyme has a molecular mass near
92 kDa and activity that was not affected by reducing or chelating agents but was
inhibited by specific synthetic serine proteinase inhibitors and the
aminopeptidase inhibitor bestatin. However, it was not inhibited by human plasma
proteinase inhibitors, nor did it inactivate any of those tested. The enzyme
possessed amidolytic activity against p-nitroanilide substrates most effectively
after alanine residues and also displayed aminopeptidase activity against non-p
nitroanilide peptides with a preference for phenylalanine. This specificity for
hydrophobic amino acid residues was corroborated by inhibition studies with
chloromethyl ketone and organophosphonate inhibitors. More interesting from a
physiological point of view is that the bioactive peptides, angiotensins I and II
and vasoactive intestinal peptide, were also hydrolyzed rapidly, indicating an
ability of peptidase IImes to act also as an oligopeptidase. Because these
bioactive peptides play a role in the inflammatory responses in allergic asthma,
our data suggest that the purified mesquite pollen peptidase IImes may be
involved in the degradation of neuro- and vasoactive peptides during pollen
initiated allergic reactions.
PMID- 9642234
TI - Localization of the functional domains of human tissue inhibitor of
metalloproteinases-3 and the effects of a Sorsby's fundus dystrophy mutation.
AB - A transient COS-7 cell expression system was used to investigate the functional
domain arrangement of tissue inhibitor of metalloproteinases-3 (TIMP-3),
specifically to assess the contribution of the amino- and carboxyl-terminal
domains of the molecule to its matrix metalloproteinase (MMP) inhibitory and
extracellular matrix (ECM) binding properties. Wild type TIMP-3 was entirely
localized to the ECM in both its glycosylated (27 kDa) and unglycosylated (24
kDa) forms. A COOH-terminally truncated TIMP-3 molecule was found to be a non-ECM
bound MMP inhibitor, whereas a chimeric TIMP molecule, consisting of the NH2
terminal domain of TIMP-2 fused to the COOH-terminal domain of TIMP-3, displayed
ECM binding, albeit with a lower affinity than the wild type TIMP-3 molecule.
Thus the functional domain arrangement of TIMP-3 is analogous to that seen in
TIMP-1 and -2, namely that the NH2-terminal domain is responsible for MMP
inhibition whereas the COOH-terminal domain is most important in mediating the
specific functions of the molecule. A mutant TIMP-3 in which serine 181 was
changed to a cysteine, found in Sorsby's fundus dystrophy, a hereditary macular
degenerative disease, was also expressed in COS-7 cells. This gave rise to an
additional 48-kDa species (possibly a TIMP-3 dimer) that retained its ability to
inhibit MMPs and localize to the ECM. These data favor the hypothesis that the
TIMP-3 mutations seen in Sorsby's fundus dystrophy contribute to disease
progression by accumulation of mutant protein rather than by the loss of
functional TIMP-3.
PMID- 9642235
TI - Guanine nucleotide exchange factors regulate specificity of downstream signaling
from Rac and Cdc42.
AB - The Rac and Cdc42 GTPases regulate diverse cellular behaviors involving the actin
cytoskeleton, gene transcription, and the activity of multiple protein and lipid
kinases. All of these pathways can potentially become activated when GTP-Rac or
GTP-Cdc42 is formed in response to external cell signals, yet it is evident that
each activity must also be able to be controlled individually. The mechanisms by
which such specificity of GTPase signaling in response to upstream stimuli is
achieved remains unclear. We investigated the action of several well
characterized guanine nucleotide exchange factors (GEFRho) to activate Rac-
and/or Cdc42-dependent kinase pathways. Coexpression studies in COS-7 cells
revealed that the ability of individual guanine nucleotide exchange factors
(GEFs) to activate the p21-activated kinase PAK1 could be dissociated from
activation of c-Jun amino-terminal kinase, even though activation of both
pathways requires the action of the GEFs on Rac and/or Cdc42. In contrast,
expression of constitutively active forms of Rac or Cdc42 effectively stimulated
both downstream kinases. We conclude that GEFs can be important determinants of
downstream signaling specificity for members of the Rho GTPase family.
PMID- 9642236
TI - Involvement of Ras in Bruton's tyrosine kinase-mediated JNK activation.
AB - Defects in Bruton's tyrosine kinase (Btk) result in B cell immunodeficiencies in
humans and mice. Recent studies showed that Btk is required for maximal
activation of JNK, a family of stress-activated protein kinases, induced by
several extracellular stimuli including interleukin (IL)-3. On the other hand, IL
3-induced JNK activation is dependent on Ras. In the present study we have
investigated whether Ras is involved in Btk-mediated JNK activation in BaF3 mouse
pro-B cells. Overexpression of wild-type Btk protein in these cells enhanced JNK
activation upon IL-3 stimulation, whereas expression of kinase-dead Btk partially
suppressed JNK activation. Induced expression of the dominant negative Ras(N17)
in the cells overexpressing wild-type Btk suppressed JNK activation. Importantly,
overexpression of Btk enhanced the level of the GTP-bound, active form of Ras in
response to IL-3 stimulation. Btk overexpression also increased the Shc-Grb2
association induced by IL-3 stimulation. Expression of either N17Ras or V12Ras
did not impose any effects on Btk kinase activity. These data collectively
indicate that Ras plays a role of an intermediary signaling protein in Btk
mediated JNK activation induced by the IL-3 signaling pathway.
PMID- 9642237
TI - Protease IV, a unique extracellular protease and virulence factor from
Pseudomonas aeruginosa.
AB - Comparisons of virulence between a Pseudomonas parent strain and an isogenic
mutant devoid of protease IV have demonstrated a significant role for this enzyme
during infection. We have characterized purified Pseudomonas aeruginosa protease
IV in terms of its biochemical and enzymatic properties, and found it to be a
unique extracellular protease. The N-terminal decapeptide sequence of protease IV
is not homologous with any published protein sequence. Protease IV has a
molecular mass of 26 kDa, an isoelectric point of 8.70, and optimum enzymatic
activity at pH 10.0 and 45 degreesC. Purified protease IV demonstrates activity
for the carboxyl side of lysine-containing peptides and can digest a number of
biologically important proteins, including immunoglobulin, complement components,
fibrinogen, and plasminogen. Protease IV is not inhibited by thiol-, carboxyl-,
or metalloproteinase inhibitors. The total loss of enzyme activity in the
presence of N-p-tosyl-L-chloromethyl ketone and the partial inhibition of enzyme
activity by diisopropyl fluorophosphate or phenylmethylsulfonyl fluoride imply
that protease IV is a serine protease. Inhibition by dithiothreitol and beta
mercaptoethanol suggests that intramolecular disulfide bonds are essential for
enzyme activity. The characteristics of this enzyme suggest that inhibitors of
serine proteases could be developed into a medication designed to arrest tissue
damage during Pseudomonas infection.
PMID- 9642238
TI - Identification and characterization of a conserved erythroid-specific enhancer
located in intron 8 of the human 5-aminolevulinate synthase 2 gene.
AB - Thirty five kilobases of sequence encompassing the human erythroid 5
aminolevulinate synthase (ALAS2) gene have been determined. Analysis revealed a
very low GC content, few repetitive elements, and evidence for the insertion of a
reverse-transcribed mRNA sequence and a neighboring gene. We have investigated
whether introns 1, 3, and 8, which correspond to DNase I-hypersensitivity sites
in the structurally related mouse ALAS2 gene, affect expression of the human
ALAS2 promoter in transient expression assays. Whereas intron 3 was marginally
inhibitory, introns 1 and 8 of the human gene stimulated promoter activity.
Intron 8 harbored a strong erythroid-specific enhancer activity which was
orientation-dependent. Deletion analysis of this region localized enhancer
activity to a fragment of 239 base pairs. Transcription factor binding sites
clustered within this region include GATA motifs and CACCC boxes, critical
regulatory sequences of many erythroid cell-expressed genes. These sites were
also identified in the corresponding intron of both the murine and canine ALAS2
genes. Mutagenesis of these conserved sites in the human intron 8 sequence and
transient expression analysis in erythroid cells established the functional
importance of one GATA motif and two CACCC boxes. The GATA motif bound GATA-1 in
vitro. The two functional CACCC boxes each bound Sp1 or a related protein in
vitro, but binding of the erythroid Kruppel-like factor and the basic Kruppel
like factor could not be detected. The intron 8 enhancer region was not activated
by GATA-1 together with Sp1 in transactivation experiments in COS-1 cells
indicating the involvement of a related Sp1 protein or of another unidentified
erythroid factor. Overall, these results demonstrate that a GATA-1-binding site
and CACCC boxes located within the human ALAS2 intron 8 are critical for the
erythroid-specific enhancer activity in transfected erythroid cells, and due to
the conserved nature of these binding sites across species, it seems likely that
these sites play a functional role in the tissue-restricted expression of the
gene in vivo.
PMID- 9642239
TI - Functional characterization of a cloned human kidney Na+:HCO3- cotransporter.
AB - Functional properties of a cloned human kidney Na+:HCO3- cotransporter (NBC-1)
were studied in cultured HEK-293 cells that were transiently transfected with NBC
1 cDNA. The Na+:HCO3- cotransporter activity was assayed as the Na+ and HCO3
dependent pHi recovery from intracellular acidosis with the use of the pH
sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. In acid-loaded
cells and in the presence of amiloride (to block Na+/H+ exchange), switching to a
Na+-containing solution (115 mM) resulted in rapid pHi recovery only in the
presence of HCO3-. This recovery was completely abolished by 300 microM 4, 4'
diisothiocyanostilbene-2,2'-disulfonic acid. Replacing the Na+ with Li+ (115 mM)
caused significant HCO3--dependent, DIDS-sensitive pHi recovery from
intracellular acidosis, with Li+ showing lower affinity than Na+. Potassium (K+)
had no affinity for the Na+:HCO3- cotransporter. The Na+-dependent HCO3-
cotransport was abolished in the presence of 0.2 mM harmaline. The Na+:HCO3-
cotransporter could also function in Na+:OH- cotransport mode, although only at
high external pH (7.8). Based on functional similarities with the mammalian
kidney experiments, we propose that NBC-1 is the proximal tubule Na+:HCO3-
cotransporter.
PMID- 9642240
TI - Cathepsin Z, a novel human cysteine proteinase with a short propeptide domain and
a unique chromosomal location.
AB - We have identified and characterized a novel human cysteine proteinase of the
papain family. A full-length cDNA for this enzyme was cloned from a human brain
cDNA library. Nucleotide sequence analysis revealed that the isolated cDNA codes
for a polypeptide of 303 amino acids, tentatively called cathepsin Z, that
exhibits structural features characteristic of cysteine proteinases. Fluorescent
in situ hybridization experiments revealed that the human cathepsin Z gene maps
to chromosome 20q13, a location that differs from all cysteine proteinase genes
mapped to date. The cDNA encoding cathepsin Z was expressed in Escherichia coli
as a fusion protein with glutathione S-transferase, and after purification, the
recombinant protein was able to degrade the synthetic peptide benzyloxycarbonyl
Phe-Arg-7-amido-4-methylcoumarin, used as a substrate for cysteine proteinases.
Northern blot analysis demonstrated that cathepsin Z is widely expressed in human
tissues, suggesting that this enzyme could be involved in the normal
intracellular protein degradation taking place in all cell types. Cathepsin Z is
also ubiquitously distributed in cancer cell lines and in primary tumors from
different sources, suggesting that this enzyme may participate in tumor
progression as reported for other cathepsins. Finally, on the basis of a series
of distinctive structural features, including diverse peptide insertions and an
unusual short propeptide, together with its unique chromosomal location among
cysteine proteinases, we propose that cathepsin Z may be the first representative
of a novel subfamily of this class of proteolytic enzymes.
PMID- 9642241
TI - Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by a
template mechanism. Evidence that calcium alleviates Gla domain antagonism of
heparin binding to factor Xa.
AB - It is believed that heparin accelerates factor Xa (FXa) inactivation by
antithrombin (AT) by conformationally activating the inhibitor rather than by
bridging AT and FXa in a ternary complex (template effect). This is derived from
kinetic studies done in the absence of Ca2+ or in the presence of EDTA. To test
the possibility that the anionic Gla domain of FXa, when not neutralized by Ca2+
ions, prevents heparin binding to FXa, the heparin and pentasaccharide dependence
of FXa inactivation by AT in both the absence (100 microM EDTA) and presence of
Ca2+ (2.5 mM) was studied using wild-type FXa and a FXa derivative that lacks the
Gla domain (GDFXa). AT inactivated both FXa derivatives similarly in both the
absence and presence of Ca2+ (k2 = 1.7-2.5 x 10(3) M-1 s-1). The active AT
binding pentasaccharide also accelerated the inactivation rates of both
derivatives similarly in both the absence and presence of Ca2+ (k2 = 5.7-8.0 x
10(5) M-1 s-1). However, in the presence of an optimum concentration of heparin (
approximately 50 nM) the inactivation rate constant of FXa in the presence of
Ca2+ (k2 = 4.4 x 10(7) M-1 s-1) was 13-fold higher than the rate constant in the
absence of Ca2+ (k2 = 3.5 x 10(6) M-1 s-1). Heparin acceleration of GDFXa
inactivation by AT was rapid and insensitive to the presence or absence of Ca2+
(k2 = 5.1-5.9 x 10(7) M-1 s-1). The additional cofactor effect of heparin with
all FXa derivatives was a bell-shaped curve, which disappeared if the ionic
strength of the reaction was increased to approximately 0.4. These results
suggest that although the major effect of heparin in acceleration of FXa
inactivation is through a heparin-induced conformational change in the reactive
site loop of AT, the template effect of heparin, nevertheless, contributes
significantly to rapid FXa inactivation at physiological Ca2+.
PMID- 9642242
TI - C5 convertase of the alternative pathway of complement. Kinetic analysis of the
free and surface-bound forms of the enzyme.
AB - Although proteolytic activation of the complement protein C5 initiates important
defensive and occasionally pathological inflammatory reactions, the enzymatic
properties of the enzymes responsible for this cleavage have never been examined.
We have studied the kinetic parameters of the C5 convertase of the alternative
pathway of complement, either bound to a zymosan surface or in its monomeric
soluble form. C5 convertase enzymatic activity was measured as a function of C5
concentration by quantitating production of C5b,6 under physiological conditions
of temperature, pH, and ionic strength. The C5 convertases appeared to follow
Michaelis-Menten kinetics and exhibited similar catalytic rate constants (kcat).
However, the surface-bound enzyme, ZymC3b,Bb had a Km (1.4 microM) that was 17
times lower than that of the soluble monomeric form of the enzyme, C3b,Bb (Km =
24 microM). The kcat for the cell-bound enzyme, ZymC3b,Bb was 0.0048 s-1 and that
for soluble C3b,Bb was 0.0110 s-1. Both forms of the enzyme had a low turnover
number at Vmax (0.23 to 0.68 C5/min/enzyme). Substituting Mg2+ for Ni2+ did not
alter the kinetic parameters but lowered the half-life of the enzyme by 5-7-fold.
The kinetic data presented demonstrate that the fluid phase C5 convertase,
C3b,Bb, can cleave C5 without the aid of a second C3b molecule. The results also
show that the greater enzymatic activity previously observed for the surface
bound C5 convertases is not due to higher catalytic efficiency but is solely due
to higher affinity for the substrate C5. In blood, C5 concentrations are 3-4-fold
below the Km determined for the surface-bound C5 convertase suggesting a direct
correlation between the local C5 concentration and production of the
anaphylatoxin C5a and the cytolytic C5b-9 complex.
PMID- 9642243
TI - Differential expression and biological effects of insulin-like growth factor
binding protein-4 and -5 in vascular smooth muscle cells.
AB - Insulin-like growth factor-I (IGF-I) plays an important role in regulating
vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis. The
bioactivity of IGF-I is modulated by a group of high affinity, specific binding
proteins (IGF-binding proteins; IGFBPs) that are present in the interstitial
fluid. Previously, we have reported that porcine VSMCs synthesize and secrete IGF
I and several forms of IGFBPs, including IGFBP-2, IGFBP-4, and IGFBP-5. In this
study, we examined the role of autocrine/paracrine secreted IGF-I in controlling
the expression of IGFBP-4 and IGFBP-5 as well as the effects of these IGFBPs in
modulating the cellular replication response to IGF-I. The concentrations of
IGFBP-4 in the conditioned medium increased significantly from <50 ng/ml to 742
+/- 105 ng/ml. This increase was associated with a decrease in the activity of an
IGF-I-regulated IGFBP-4 protease. In contrast, the synthesis of IGFBP-5 was
inversely correlated with culture density, and its concentration decreased from
792 +/- 91 to 44 +/- 14 ng/ml. IGFBP-5 mRNA in sparse cultures was 3-fold higher
compared with those in confluent cultures. This culture density-dependent change
in IGFBP-5 mRNA correlated closely with endogenous IGF-I levels. Since treatment
of VSMC with exogenous IGF-I increased IGFBP-5 mRNA levels, we neutralized the
effect of endogenously secreted IGF-I with an anti-IGF-I antibody to determine if
it would alter IGFBP-5 mRNA abundance. This resulted in a 4.4-fold decrease in
IGFBP-5 mRNA levels. When added together with IGF-I, exogenous IGFBP-4 inhibited
IGF-I-induced DNA synthesis in a concentration-dependent manner. IGFBP-5, on the
other hand, potentiated the effect of IGF-I. Therefore, IGFBP-4 and IGFBP-5
appear to be differentially regulated by autocrine/paracrine IGF-I through
distinct mechanisms. These two proteins, in turn, play opposing roles in
modulating IGF-I action in stimulating VSMC proliferation.
PMID- 9642244
TI - Recognition of a human arrest site is conserved between RNA polymerase II and
prokaryotic RNA polymerases.
AB - DNA sequences that arrest transcription by either eukaryotic RNA polymerase II or
Escherichia coli RNA polymerase have been identified previously. Elongation
factors SII and GreB are RNA polymerase-binding proteins that enable readthrough
of arrest sites by these enzymes, respectively. This functional similarity has
led to general models of elongation applicable to both eukaryotic and prokaryotic
enzymes. Here we have transcribed with phage and bacterial RNA polymerases, a
human DNA sequence previously defined as an arrest site for RNA polymerase II.
The phage and bacterial enzymes both respond efficiently to the arrest signal in
vitro at limiting levels of nucleoside triphosphates. The E. coli polymerase
remains in a template-engaged complex for many hours, can be isolated, and is
potentially active. The enzyme displays a relatively slow first-order loss of
elongation competence as it dwells at the arrest site. Bacterial RNA polymerase
arrested at the human site is reactivated by GreB in the same way that RNA
polymerase II arrested at this site is stimulated by SII. Very efficient
readthrough can be achieved by phage, bacterial, and eukaryotic RNA polymerases
in the absence of elongation factors if 5-Br-UTP is substituted for UTP. These
findings provide additional and direct evidence for functional similarity between
prokaryotic and eukaryotic transcription elongation and readthrough mechanisms.
PMID- 9642245
TI - Limitations of the mass isotopomer distribution analysis of glucose to study
gluconeogenesis. Heterogeneity of glucose labeling in incubated hepatocytes.
AB - We previously reported (Previs, S. F., Fernandez, C. A., Yang, D., Soloviev, M.
V., David, F., and Brunengraber, H. (1995) J. Biol. Chem. 270, 19806-19815) that
glucose made in isolated livers from starved rats perfused with physiological
concentrations of lactate, pyruvate, and either [2-13C]- or [U-13C3]glycerol had
a mass isotopomer distribution incompatible with glucose being made from a
homogeneously labeled pool of triose phosphates. Similar data were obtained in
live rats infused with [U-13C3]glycerol. We ascribed the labeling heterogeneity
to major decreases in glycerol concentration and enrichment across the liver. We
concluded that [13C]glycerol is unsuitable for tracing the contribution of
gluconeogenesis to total glucose production. We now report isotopic heterogeneity
of gluconeogenesis in hepatocytes, even when all cells are in contact with
identical concentrations and enrichments of gluconeogenic substrates. Total rat
hepatocytes were incubated with concentrations of glycerol, lactate, and pyruvate
that were kept constant by substrate infusions. To modulate competition between
substrates, the (glycerol)/(lactate + pyruvate) infusion ratio ranged from 0.23
to 3. 60. Metabolic and isotopic steady states were achieved in all cases. The
apparent contribution of gluconeogenesis to glucose production (f) was calculated
from the mass isotopomer distribution of glucose. When all substrates were 13C
labeled, f was 97%, as expected in glycogen-deprived hepatocytes. As the infusion
ratio ([13C]glycerol)/(lactate + pyruvate) increased, f increased from 73% to
94%. In contrast, as the infusion ratio (glycerol)/([13C]lactate + [13C]pyruvate)
increased, f decreased from 93% to 76%. In all cases, f increased with the rate
of supply of the substrate that was labeled. Variations in f show that the 13C
labeling of triose phosphates was not equal in all hepatocytes, even when exposed
to the same substrate concentrations and enrichments. We also showed that
zonation of glycerol kinase activity is minor in rat liver. We conclude that
zonation of other processes than glycerol phosphorylation contributes to the
heterogeneity of triose phosphate labeling from glycerol in rat liver.
PMID- 9642246
TI - Conversion of temperature-sensitive to -resistant gene expression due to
mutations in the promoter region of the melibiose operon in Escherichia coli.
AB - The melibiose utilization system of Escherichia coli W3133, a derivative of K12,
is nonfunctional between 37 and 42 degreesC. The reason for this temperature
sensitivity was thought to be that the melibiose transporter (MelB) of W3133
cells was temperature-sensitive. A mutant W3133-2 has been isolated as a
temperature-resistant strain that can utilize melibiose between 37 and 42
degreesC. However, we found that the melibiose transporter of the W3133-2 was
still temperature-sensitive. Half-life activities of the melibiose transporter at
37 degreesC (or 40 degreesC) in both E. coli W3133 and W3133-2 were exactly the
same. Furthermore, we found that the nucleotide sequence of coding region of the
melB structural gene (the second gene of the melibiose operon) of W3133-2 was
exactly the same as that of W3133. Activity of alpha-galactosidase (product of
the first gene, melA, of the melibiose operon) of W3133 cells grown at 40
degreesC was very low, although that of W3133-2 cells grown at 40 degreesC was
high. These observations suggested that expression of the melibiose operon in
W3133 is also temperature-sensitive. In fact, we found that the expression in
W3133 cells was temperature-sensitive, while that in W3133-2 cells was
temperature-resistant, by analyzing mRNA levels using the Northern blot method.
Furthermore, we identified mutations in the promoter region of the melibiose
operon of W3133-2 that resulted in the elongation of an 18 nucleotide inverted
repeat sequence to a 28-nucleotide repeat sequence present immediately upstream
of the -35 region. This may stabilize a possible stem structure due to the
inverted repeat at 37-42 degreesC.
PMID- 9642247
TI - Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to
rat cerebellar membranes correlates with agonist-induced decreases in GDP
affinity.
AB - The relationship between GDP and cannabinoid-stimulated [35S]guanosine-5'-O-(3
thiotriphosphate) ([35S]GTPgammaS) binding was investigated in rat cerebellar
membranes. Kinetic analyses showed that [35S]GTPgammaS binding reached steady
state levels and that the association rate was increased by the agonist WIN 55212
2 proportional to the concentration of GDP. Dissociation of [35S]GTPgammaS
occurred with two rates (t1/2 = 7 and 170 min), and WIN 55212-2 increased the
proportion of sites exhibiting the faster rate. Without GDP, [35S]GTPgammaS bound
to membranes with high and low affinity, and WIN 55212-2 had no effect. With 30
microM GDP, [35S]GTPgammaS bound to low and intermediate affinity sites, and WIN
55212-2 induced high affinity [35S]GTPgammaS binding without affecting low
affinity sites. GDP competed for high affinity [35S]GTPgammaS binding with high
and intermediate affinity in the absence of WIN 55212-2 and with high and low
affinity in the presence of WIN 55212-2. Cannabinoid ligands displayed
differential abilities to maximally stimulate [35S]GTPgammaS binding in the
presence of GDP. Efficacy differences among ligands increased with increasing GDP
concentrations. GDP competition curves revealed that agonists induced low
affinity GDP Ki values that were proportional to agonist Emax values, indicating
that agonist efficacy is determined by displacement of GDP from G-proteins.
PMID- 9642248
TI - Inhibition of activating transcription factor 1- and cAMP-responsive element
binding protein-activated transcription by an intracellular single chain Fv
fragment.
AB - Activating transcription factor 1 (ATF1) and cAMP-responsive element (CRE)
binding protein (CREB) activate transcription through CREs located in the
promoters of cellular and viral genes. We previously described a monoclonal
antibody (mAb41.4) that prevents ATF1 binding to DNA and reduces CRE-driven
promoter activity in vitro (Orten, D. J., Strawhecker, J. M., Sanderson, S. D.,
Huang, D., Prytowsky, M. B. , and Hinrichs, S. H. (1994) J. Biol. Chem. 269,
32254-32263). A single chain Fv (scFv) fragment from the mAb41.4-expressing
hybridoma was generated to provide a means to investigate transcription factor
function via intracellular expression of the scFv fragment. The affinity of scFv4
(subgroup: VL kappa-III, VH miscellaneous) for ATF1 was similar to that of the
parental mAb and the Fab fragment, but it demonstrated greater inhibitory
activity and reacted with CREB. scFv4 disrupted the binding of both ATF1 and CREB
in electrophoretic mobility shift assays and reduced expression of CRE-driven
expression in vitro. Transient expression of scFv had no effect on the non-CRE
containing adenovirus major late promoter. The proliferating cell nuclear antigen
promoter, containing two CREs, was significantly more sensitive to inhibition by
scFv than the cytomegalovirus immediate-early promoter, containing five CREs.
Cotransfection of either ATF1 or CREB in the presence of scFv restored basal
levels of expression. The intracellular expression of scFv provides a unique
means to investigate the roles of the transcription factors ATF1 and CREB.
PMID- 9642249
TI - NF-Y organizes the gamma-globin CCAAT boxes region.
AB - The CCAAT-binding activator NF-Y is formed by three evolutionary conserved
subunits, two of which contain putative histone-like domains. We investigated NF
Y binding to all CCAAT boxes of globin promoters in direct binding, competition,
and supershift electrophoretic mobility shift assay; we found that the alpha,
zeta, and proximal gamma CCAAT boxes of human and the prosimian Galago bind
avidly, and distal gamma CCAAT boxes have intermediate affinity, whereas the
epsilon and beta sequences bind NF-Y very poorly. We developed an efficient in
vitro transcription system from erythroid K562 cells and established that both
the distal and the proximal CCAAT boxes are important for optimal gamma-globin
promoter activity. Surprisingly, NF-Y binding to a mutated distal CCAAT box (a C
to T at position -114) is remarkably increased upon occupancy of the high
affinity proximal element, located 27 base pairs away. Shortening the distance
between the two CCAAT boxes progressively prevents simultaneous CCAAT binding,
indicating that NF-Y interacts in a mutually exclusive way with CCAAT boxes
closer than 24 base pairs apart. A combination of circular permutation and
phasing analysis proved that (i) NF-Y-induced angles of the two gamma-globin
CCAAT boxes have similar amplitudes; (ii) occupancy of the two CCAAT boxes leads
to compensatory distortions; (iii) the two NF-Y bends are spatially oriented with
combined twisting angles of about 100 degrees. Interestingly, such distortions
are reminiscent of core histone-DNA interactions. We conclude that NF-Y binding
imposes a high level of functionally important coordinate organization to the
gamma-globin promoter.
PMID- 9642250
TI - Evidence for a ligand interaction site at the amino-terminus of the parathyroid
hormone (PTH)/PTH-related protein receptor from cross-linking and mutational
studies.
AB - Low resolution mutational studies have indicated that the amino-terminal
extracellular domain of the rat parathyroid hormone (PTH)/PTH-related protein
(PTHrP) receptor (rP1R) interacts with the carboxyl-terminal portion of PTH-(1
34) or PTHrP-(1-36). To further define ligand-receptor interactions, we prepared
a fully functional photoreactive analog of PTHrP, [Ile5,Bpa23,Tyr36]PTHrP-(1-36)
amide ([Bpa23]PTHrP, where Bpa is p-benzoyl-L-phenylalanine). Upon photolysis,
radioiodinated [Bpa23]PTHrP covalently and specifically bound to the rP1R. CNBr
cleavage of the broad approximately 80-kDa complex yielded a radiolabeled
approximately 9-kDa non-glycosylated protein band that could potentially be
assigned to rP1R residues 23-63, Tyr23 being the presumed amino-terminus of the
receptor. This assignment was confirmed using a mutant rP1R (rP1R-M63I) that
yielded, upon photoligand binding and CNBr digestion, a broad protein band of
approximately 46 kDa, which was reduced to a sharp band of approximately 20 kDa
upon deglycosylation. CNBr digestion of complexes formed with two additional rP1R
double mutants (rP1R-M63I/L40M and rP1R-M63I/L41M) yielded non-glycosylated
protein bands that were approximately 6 kDa in size, indicating that [Bpa23]PTHrP
cross-links to amino acids 23-40 of the rP1R. This segment overlaps a receptor
region previously identified by deletion mapping to be important for ligand
binding. Alanine scanning of this region revealed two residues, Thr33 and Gln37,
as being functionally involved in ligand binding. Thus, the convergence of
photoaffinity cross-linking and mutational data demonstrates that the extreme
amino-terminus of the rP1R participates in ligand binding.
PMID- 9642251
TI - Patch clamp studies on ion pumps of the cytoplasmic membrane of Escherichia coli.
Formation, preparation, and utilization of giant vacuole-like structures
consisting of everted cytoplasmic membrane.
AB - Formation of giant protoplasts from normal Escherichia coli cells resulted in the
formation of giant vacuole-type structures (which we designate as provacuoles) in
the protoplasts. Electron microscopic observation revealed that these provacuoles
were surrounded by a single membrane. We detected inner (cytoplasmic) membrane
proteins in the provacuolar membrane but not outer membrane proteins. Biochemical
analyses revealed that the provacuoles consist of everted cytoplasmic membranes.
We applied the patch clamp method to the giant provacuoles. We have succeeded in
measuring current that represents inward movement of H+ because of respiration
and to ATP hydrolysis by the FoF1-ATPase. Such current was inhibited by
inhibitors of the respiratory chain or FoF1-ATPase. This method is applicable for
analyses of ion channels, ion pumps, or ion transporters in E. coli or other
microorganisms.
PMID- 9642252
TI - Applied pressure enhances cell proliferation through mitogen-activated protein
kinase activation in mesangial cells.
AB - Progressive renal diseases lead to prolonged glomerular hypertension, which
induces the proliferation of mesangial cells. This proliferation is thought to be
involved in the development of renal injury. Here we investigate mitogen
activated protein kinase (MAPK) activation and cell proliferation in mesangial
cells under conditions of high pressure. After pressure-load, the phosphorylation
level of MAPK (at Tyr-204) increases rapidly with a peak at 1 min, although the
amount of MAPK remains almost constant during pressure-load. To confirm the
activation of MAPK, we carried out an immunoprecipitation-kinase assay. MAPK
activity during pressure-load shows kinetics similar to that of the tyrosine
phosphorylation. In contrast, c-Jun N-terminal kinase 1 (JNK1) phosphorylation
falls below basal levels in response to high pressure. Immunocytochemical
observations show phosphorylated MAPK in the nucleus at 10 min. The expression of
c-Fos, a nuclear transcription factor, is induced by high pressure, and the
induction is significantly inhibited by PD98059 (50 microM), an upstream
MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitor of MAPK. The
expression of the c-Jun that is induced by JNK1 activation remains unchanged
during pressure-load. MAPK phosphorylation and cell proliferation by applied
pressure are significantly inhibited by genistein, a tyrosine kinase inhibitor in
a dose-dependent manner, but not by protein kinase C inhibitors, chelerythrine
and GF109203X. Genistein also blocks pressure-induced tyrosine phosphorylation of
proteins with molecular masses of 35, 53, and 180 kDa. To clarify the
physiological role in MAPK activation under high pressure conditions, we
transfected antisense MAPK DNA into mesangial cells. The antisense DNA (2 microM)
inhibited MAPK expression by 80% compared with expression in the presence of
sense or scrambled DNA, and significantly blocked pressure-induced cell
proliferation. Treatment of cells with MEK inhibitor also produced a similar
result. MEK inhibitor strongly suppresses DNA synthesis induced by pressure-load.
Cyclin D1 expression is significantly increased under high pressure conditions,
and the increase is blocked by treatment with MEK inhibitor. These findings show
that pressure-load, a novel activator of MAPK, induces the activation of tyrosine
kinases, and enhances the proliferation of mesangial cells, probably through
cyclin D1 expression.
PMID- 9642253
TI - Identification of a potential effector pathway for the trimeric Go protein
associated with secretory granules. Go stimulates a granule-bound
phosphatidylinositol 4-kinase by activating RhoA in chromaffin cells.
AB - Besides having a role in signal transduction, heterotrimeric G proteins may be
involved in membrane trafficking events. In chromaffin cells, Go is associated
with secretory organelles, and its activation inhibits the ATP-dependent priming
of exocytosis. By using permeabilized cells, we previously described that the
control exerted by the granule-bound Go on exocytosis may be related to effects
on the cortical actin network through a sequence possibly involving Rho. To
provide further insight into the function of Rho in exocytosis, we focus here on
its intracellular localization in chromaffin cells. By immunoreplica analysis,
immunoprecipitation, and confocal immunofluorescence, we found that RhoA is
specifically associated with the membrane of secretory chromaffin granules.
Parallel subcellular fractionation experiments revealed the occurrence of a
mastoparan-stimulated phosphatidylinositol 4-kinase activity in purified
chromaffin granule membranes. This stimulatory effect of mastoparan was mimicked
by GAP-43, an activator of the granule-associated Go, and specifically inhibited
by antibodies against Galphao. In addition, Clostridium botulinum C3 exoenzyme
completely blocked the activation of phosphatidylinositol 4-kinase by mastoparan.
We propose that the control exerted by Go on peripheral actin and exocytosis is
related to the activation of a downstream RhoA-dependent phosphatidylinositol 4
kinase associated with the membrane of secretory granules.
PMID- 9642254
TI - Induction of the erythropoietin receptor gene and acquisition of responsiveness
to erythropoietin by stem cell factor in HML/SE, a human leukemic cell line.
AB - HML/SE is a cytokine-dependent cell line established from childhood acute
megakaryoblastic leukemia. Granulocyte-macrophage colony-stimulating factor or
stem cell factor (SCF) alone could stimulate proliferation of HML/SE cells,
however interleukin-3, interleukin-6, granulocyte colony-stimulating factor and
thrombopoietin could not. Although erythropoietin (EPO) alone stimulated neither
proliferation nor differentiation of HML/SE cells, it did stimulate proliferation
of HML/SE cells and production of hemoglobin in the presence of SCF. SCF
activated the human EPO receptor promoter and induced EPO receptor gene
expression. Given these results, we speculate that HML/SE cells acquired
responsiveness to EPO via the EPO receptor induced by SCF. Mutation analysis of
putative transcription factor binding sites in the human EPO receptor promoter
suggested that Sp1, rather than the GATA-1 binding site, contributed to the
induction of the hEPOR gene. Although it is well documented that hematopoietic
stem cells and primitive progenitors require both an early-acting cytokine and a
lineage-specific cytokine to differentiate to a certain lineage, related
mechanisms are not well understood. HML/SE may serve as an excellent model system
to analyze functions of early-acting cytokine SCF and lineage-specific cytokine
EPO related to proliferation and differentiation of hematopoietic stem cells.
PMID- 9642255
TI - Characterization of a variant iron protein of nitrogenase that is impaired in its
ability to adopt the MgATP-induced conformational change.
AB - An Azotobacter vinelandii nitrogenase iron protein mutant has been created which
contains an alanine to glycine substitution at amino acid 157. The strain
expressing this mutant Fe protein is able to grow under nitrogen-fixing
conditions. This contrasts with an A. vinelandii strain described previously
which is unable to grow under nitrogen-fixing conditions and which expresses an
Fe protein variant that has an alanine to serine mutation at position 157. The
A157S Fe protein was unable to support substrate reduction by nitrogenase because
of an inability to undergo a required MgATP-induced conformational change.
Although the A157G strain grows at 55% of the rate of the wild-type strain,
purified A157G Fe protein is only able to support substrate reduction in in vitro
assays at a rate that is approximately 20% of the rate supported by the wild-type
Fe protein. Electron paramagnetic resonance, circular dichroism spectroscopies,
and enzymatic activity data indicate that the A157G Fe protein adopts the correct
conformation upon the binding of MgATP. However, kinetic studies using chelation
show that this protein undergoes the conformational change more slowly than the
wild-type protein. Thus, this mutant has lower activity because of an impaired
ability to undergo this conformational change. Comparison of two available x-ray
crystal structures of the native Fe protein alone and complexed with the MoFe
protein has provided us with a model to explain the change in activity in alanine
157 mutants. Steric interactions with the side chain of residue 157 influence the
protein's ability to undergo the initial MgATP-induced conformational change. In
the case of the A157G mutant, however, once the correct conformation is attained,
the protein can participate in all subsequent reactions including complex
formation, electron transfer, and MgATP hydrolysis. Thus, the role of alanine 157
is to stabilize the proper initial conformation upon MgATP binding.
PMID- 9642256
TI - PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in
its oligomerization, subcellular localization, substrate specificity, and
regulation.
AB - Methylation is one of the many post-translational modifications that modulate
protein function. Although asymmetric NG,NG-dimethylation of arginine residues in
glycine-arginine-rich domains of eucaryotic proteins, catalyzed by type I protein
arginine N-methyltransferases (PRMT), has been known for some time, members of
this enzyme class have only recently been cloned. The first example of this type
of enzyme, designated PRMT1, cloned because of its ability to interact with the
mammalian TIS21 immediate-early protein, was then shown to have protein arginine
methyltransferase activity. We have now isolated rat and human cDNA orthologues
that encode proteins with substantial sequence similarity to PRMT1. A recombinant
glutathione S-transferase (GST) fusion product of this new rat protein, named
PRMT3, asymmetrically dimethylates arginine residues present both in the designed
substrate GST-GAR and in substrate proteins present in hypomethylated extracts of
a yeast rmt1 mutant that lacks type I arginine methyltransferase activity; PRMT3
is thus a functional type I protein arginine N-methyltransferase. However, rat
PRMT1 and PRMT3 glutathione S-transferase fusion proteins have distinct enzyme
specificities for substrates present in both hypomethylated rmt1 yeast extract
and hypomethylated RAT1 embryo cell extract. TIS21 protein modulates the
enzymatic activity of recombinant GST-PRMT1 fusion protein but not the activity
of GST-PRMT3. Western blot analysis of gel filtration fractions suggests that
PRMT3 is present as a monomer in RAT1 cell extracts. In contrast, PRMT1 is
present in an oligomeric complex. Immunofluorescence analysis localized PRMT1
predominantly to the nucleus of RAT1 cells. In contrast, PRMT3 is predominantly
cytoplasmic.
PMID- 9642257
TI - Gbeta binding to GIRK4 subunit is critical for G protein-gated K+ channel
activation.
AB - The cardiac G protein-gated K+ channel, IKACh, is directly activated by G protein
beta gamma subunits (Gbeta gamma). IKAChis composed of two inward rectifier K+
channel subunits, GIRK1 and GIRK4. Gbeta gamma binds to both GIRK1 and GIRK4
subunits of the heteromultimeric IKACh. Here we delineate the Gbeta gamma binding
regions of IKACh by studying direct Gbeta gamma interaction with native purified
IKACh, competition of this interaction with peptides derived from GIRK1 or GIRK4
amino acid sequences, mutational analysis of regions implicated in Gbeta gamma
binding, and functional expression of mutated subunits in mammalian cells. Only
two GIRK4 peptides, containing amino acids 209-225 or 226-245, effectively
competed for Gbeta gamma binding. A single point mutation introduced into GIRK4
at position 216 (C216T) dramatically reduced the potency of the peptide in
inhibiting Gbeta gamma binding and Gbeta gamma activation of expressed
GIRK1/GIRK4(C216T) channels. Conversion of 5 amino acids in GIRK4 (226-245) to
the corresponding amino acids found in the G protein-insensitive IRK1 channel,
completely abolished peptide inhibition of Gbeta gamma binding to IKACh and Gbeta
gamma activation of GIRK1/mutant GIRK4 channels. We conclude from this data that
Gbeta gamma binding to GIRK4 is critical for IKACh activation.
PMID- 9642258
TI - E-cadherin regulates anchorage-independent growth and survival in oral squamous
cell carcinoma cells.
AB - Integrin-basement membrane interactions provide essential signals that promote
survival and growth of epithelial cells, whereas loss of such adhesions triggers
programmed cell death. We found that HSC-3 human squamous carcinoma cells
survived and grew readily as monolayers, but when they were suspended as single
cells, they ceased proliferating and entered into the apoptotic death pathway,
characterized by DNA fragmentation. In contrast, if the suspended carcinoma cells
were permitted to form E-cadherin-mediated multicellular aggregates, they not
only survived but proliferated. However, aggregated normal keratinocytes were
unable to survive in suspension culture and rapidly became apoptotic. Anchorage
independence and resistance to apoptosis of HSC-3 cell aggregates required high
levels of extracellular Ca2+ and was inhibited with function-perturbing anti-E
cadherin antibody. Resistance to suspension-induced apoptosis in cell aggregates
paralleled the up-regulation of Bcl-2 but occurred in the absence of focal
adhesion kinase activation. Analysis of suspension-induced death in a set of
cloned squamous epithelial cell lines with different levels of E-cadherin
expression revealed that receptor-positive cell clones evaded apoptosis and
proliferated in three-dimensional aggregate culture, whereas cadherin-negative
clones failed to survive. Collectively, these observations indicate that cadherin
mediated intercellular adhesions generate a compensatory mechanism that promotes
anchorage-independent growth and suppresses apoptosis.
PMID- 9642259
TI - Structure of tetrameric human phenylalanine hydroxylase and its implications for
phenylketonuria.
AB - Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to
L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine.
Mutations in the human PheOH gene cause phenylketonuria, a common autosomal
recessive metabolic disorder that in untreated patients often results in varying
degrees of mental retardation. We have determined the crystal structure of human
PheOH (residues 118-452). The enzyme crystallizes as a tetramer with each monomer
consisting of a catalytic and a tetramerization domain. The tetramerization
domain is characterized by the presence of a domain swapping arm that interacts
with the other monomers forming an antiparallel coiled-coil. The structure is the
first report of a tetrameric PheOH and displays an overall architecture similar
to that of the functionally related tyrosine hydroxylase. In contrast to the
tyrosine hydroxylase tetramer structure, a very pronounced asymmetry is observed
in the phenylalanine hydroxylase, caused by the occurrence of two alternate
conformations in the hinge region that leads to the coiled-coil helix.
Examination of the mutations causing PKU shows that some of the most frequent
mutations are located at the interface of the catalytic and tetramerization
domains. Their effects on the structural and cellular stability of the enzyme are
discussed.
PMID- 9642260
TI - RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase.
AB - Through specific interactions with members of the tumor necrosis receptor (TNFR)
family, adapter molecules such as the serine/threonine (Ser/Thr) kinase RIP
mediate divergent signaling pathways including NF-kappaB activation and cell
death. In this study, we have identified and characterized a novel 61-kDa protein
kinase related to RIP that is a component of both the TNFR-1 and the CD40
signaling complexes. Receptor interacting protein-2 (RIP2) contains an N-terminal
domain with homology to Ser/Thr kinases and a C-terminal caspase activation and
recruitment domain (CARD), a homophilic interaction motif that mediates the
recruitment of caspase death proteases. Overexpression of RIP2 signaled both NF
kappaB activation and cell death. Mutational analysis revealed the pro-apoptotic
function of RIP2 to be restricted to its C-terminal CARD domain, whereas the
intact molecule was necessary for NF-kappaB activation. RIP2 interacted with
other members of the TNFR-1 signaling complex, including inhibitor of apoptosis
protein cIAP1 and with members of the TNFR-associated factor (TRAF) family,
specifically TRAF1, TRAF5, and TRAF6, but not with TRAF2, TRAF3, or TRAF4. These
TRAF interactions mediate the recruitment of RIP2 to receptor signaling
complexes.
PMID- 9642261
TI - Human ecalectin, a variant of human galectin-9, is a novel eosinophil
chemoattractant produced by T lymphocytes.
AB - A 1.6-kilobase pair cDNA was isolated from a human T-cell-derived expression
library that encodes a novel eosinophil chemoattractant (designated ecalectin)
expressed during allergic and parasitic responses. Based on its deduced amino
acid sequence, ecalectin is a 36-kDa protein consisting of 323 amino acids.
Although ecalectin lacks a hydrophobic signal peptide, it is secreted from
mammalian cells. Ecalectin is not related to any known cytokine or chemokine but
rather is a variant of human galectin-9, a member of the large family of animal
lectins that have affinity for beta-galactosides. Recombinant ecalectin,
expressed in COS cells and insect cells, exhibited potent eosinophil
chemoattractant activity and attracted eosinophils in vitro and in vivo in a dose
dependent manner but not neutrophils, lymphocytes, or monocytes. The finding that
the ecalectin transcript is present in abundance in various lymphatic tissues and
that its expression increases substantially in antigen-activated peripheral blood
mononuclear cells suggests that ecalectin is an important T-cell-derived
regulator of eosinophil recruitment in tissues during inflammatory reactions. We
believe that this is the first report of the expression of an immunoregulatory
galectin expressed by a T-cell line that is selective for eosinophils.
PMID- 9642262
TI - Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic
acid-induced apoptosis in cancer cells.
AB - BAG-1 (also known as RAP46) is an anti-apoptotic protein, which has been shown
previously to interact with a number of nuclear hormone receptors, including
receptors for glucocorticoid, estrogen, and thyroid hormone. We show here that
BAG-1 also interacts with retinoic acid receptor (RAR). Gel retardation assays
demonstrated that in vitro translated BAG-1 protein could effectively inhibit the
binding of RAR but not retinoid X receptor (RXR) to a number of retinoic acid
(RA) response elements (RAREs). A glutathione S-transferase-BAG-1 fusion protein
also specifically bound RAR but not RXR. Interaction of BAG-1 and RAR could also
be demonstrated by yeast two-hybrid assays. In transient transfection assays, co
transfection of BAG-1 expression plasmid inhibited the transactivation activity
of RAR/RXR heterodimers but not RXR/RXR homodimers. When stably expressed in
breast cancer cell lines, BAG-1 inhibited binding of RAR/RXR heterodimer to a
number of RAREs and suppressed RA-induced growth inhibition and apoptosis. In
addition, RA-induced suppression of Bcl-2 expression was abrogated by
overexpression of BAG-1. These results demonstrate that BAG-1 can regulate
retinoid activities through its interaction with RAR and suggest that elevated
levels of BAG-1 protein could potentially contribute to retinoid resistance in
cancer cells.
PMID- 9642263
TI - Human ADAM 12 (meltrin alpha) is an active metalloprotease.
AB - The ADAMs (a disintegrin and metalloprotease) are a family of multidomain
proteins with structural homology to snake venom metalloproteases. We recently
described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this
report we provide evidence that the metalloprotease domain of ADAM 12 is
catalytically active. We used the trapping mechanism of alpha2-macroglobulin to
assay for protease activity of wild-type and mutant ADAM 12 proteins produced in
a COS cell transfection system. We found that ADAM 12 is synthesized as a
zymogen, with the prodomain maintaining the metalloprotease in a latent form,
probably by means of a cysteine switch. The zymogen could be activated chemically
by alkylation with N-ethylmaleimide. Cleavage of the prodomain at a site for a
furin-like endopeptidase resulted in an ADAM 12 protein with proteolytic
activity. The protease activity was sensitive to inhibition by 1,10
phenanthroline and could be eliminated by mutation of the critical glutamate
residue at the active site. The demonstration that the ADAM 12 metalloprotease
domain is functional may have important implications for future studies that
explore the role of ADAM 12 protein in development and disease.
PMID- 9642264
TI - The mini-hemoglobins in neural and body wall tissue of the nemertean worm,
Cerebratulus lacteus.
AB - Hemoglobin (Hb) occurs in circulating red blood cells, neural tissue, and body
wall muscle tissue of the nemertean worm, Cerebratulus lacteus. The neural and
body wall tissue each express single major Hb components for which the amino acid
sequences have been deduced from cDNA and genomic DNA. These 109-residue globins
form the smallest stable Hbs known. The globin genes have three exons and two
introns with splice sites in the highly conserved positions of most globin genes.
Alignment of the sequences with those of other globins indicates that the A, B,
and H helices are about one-half the typical length. Phylogenetic analysis
indicates that shortening results in a small tendency of globins to group
together regardless of their actual relationships. The neural and body wall Hbs
in situ are half-saturated with O2 at 2.9 and 4.1 torr, respectively. The Hill
coefficient for the neural Hb in situ, approximately 2.9, suggests that the
neural Hb self-associates in the deoxy state at least to tetramers at the 2-3 mM
(heme) concentration estimated in the cells. The Hb must dissociate upon
oxygenation and dilution because the weight-average molecular mass of the HbO2 in
vitro is only about 18 kDa at 2-3 microM heme concentration. Calculations suggest
that the Hb can function as an O2 store capable of extending neuronal activity in
an anoxic environment for 5-30 min.
PMID- 9642265
TI - Tyrosine and tryptophan act through the same binding site at the dimer interface
of yeast chorismate mutase.
AB - Tyrosine and tryptophan are the regulators of the dimeric yeast chorismate
mutase. Biochemical studies reveal two binding sites per molecule for both
effectors, tyrosine or tryptophan. A single binding site is built up by helix 8
and helices 4 and 5 of two different subunits. The binding sites have been
analyzed in the active enzyme by site directed mutagenesis of critical codons of
the coding gene, ARO7. Gly-141 and Ser-142, which both reside on helix 8, are
involved in the binding of tyrosine or tryptophan presumably by interacting
specifically with the amino- and carboxylate-groups of these amino acid
effectors. Interaction with Thr-145 of helix 8 is required for a strong tyrosine
binding to the allosteric site. Replacement of Arg-75, which connects helices 4
and 5 or of Arg-76, which is part of helix 5 by alanine residues, resulted in
unregulated enzymes. These two residues are bonded to the carboxylate group and
phenolic hydroxyl group of tyrosine, respectively, but do not interact with
tryptophan by hydrogen bonding in the crystal structures. Phenylalanine, which
has low binding affinity slightly activated the chorismate mutase. A T145V mutant
chorismate mutase, however, showed increased activation by phenylalanine. Our
results support a mechanism by which tyrosine contracts the allosteric site by
interacting with its phenolic hydroxyl group. Tryptophan works in an inverse way
by opening the allosteric site through the steric size of its side chain.
PMID- 9642266
TI - Mutations at nonliganding residues Tyr-85 and Glu-83 in the N-lobe of human serum
transferrin. Functional second shell effects.
AB - The x-ray crystal structure of the N-lobe of human serum transferrin has shown
that there is a hydrogen bond network, the so-called "second shell," around the
transferrin iron binding site. Tyrosine at position 85 and glutamic acid at
position 83 are two nonliganding residues in this network in the human serum
transferrin N-lobe (hTF/2N). Mutation of each of these two amino acids has a
profound effect on the metal binding properties of hTF/2N. When Tyr-85 is mutated
to phenylalanine, iron release from the resulting mutant Y85F is much more facile
than from the parent protein. Elimination of the hydrogen bond between Tyr-85 and
Lys-296 appears to interfere with the "di-lysine (Lys-206-Lys-296) trigger,"
which affects the iron binding stability of the protein. Surprisingly, mutation
of Glu-83 to alanine leads to the absence of one of the normal iron binding
ligands; introduction of a monovalent anion is able to restore the normal first
coordination sphere. The missing ligand appears to be His-249, as revealed by
comparison of the metal binding behaviors of mutants H249Q and E83A and
structural analysis. Glu-83 has a strong H bond linkage with His-249 in apo
hTF/2N, which helps to hold the His-249 in the proper position for iron binding.
Disabling Glu-83 by mutation to an alanine seriously disturbs the H bond network,
allowing His-249 to move away. A monovalent anion can help reestablish the normal
network by providing a negative charge near the position of Glu-83 to reach
charge balance, so that ligand His-249 is available again for iron binding.
PMID- 9642267
TI - A B-cell-specific DNA recombination complex.
AB - We have purified and biochemically characterized a multiprotein complex
designated SWAP. In a DNA transfer assay, SWAP preferentially recombines
("swaps") sequences derived from Ig heavy chain switch regions. We identified
four of the proteins in the SWAP complex: B23 (nucleophosmin), C23 (nucleolin),
poly(ADP-ribose) polymerase (PARP), and SWAP-70. The first three are proteins
known to be present in most cells. B23 promotes single-strand DNA reannealing and
the formation of joint molecules in a D-loop assay between homologous, but also
between Smu and Sgamma sequences. SWAP-70 is a novel protein of 70 kDa. Its cDNA
was cloned and sequenced, and the protein was overexpressed in Escherichia coli.
SWAP-70 protein expression was found only in B lymphocytes that had been induced
to switch to various Ig isotypes and in switching B-cell lines. SWAP-70 is a
nuclear protein, has a weak affinity for DNA, binds ATP, and forms specific, high
affinity complexes with B23, C23, and poly(ADP-ribose) polymerase. These findings
are consistent with SWAP being the long elusive "switch recombinase" and with
SWAP-70 being the specific recruiting element that assembles the switch
recombinase from universal components.
PMID- 9642268
TI - Identification of the binding site on cytochrome P450 2B4 for cytochrome b5 and
cytochrome P450 reductase.
AB - A model of cytochrome P450 2B4, which was constructed by homology modeling with
the four known crystal structures of the cytochromes P450 (Chang, T.-T.,
Stiffelman, O. B., Vakser, I. A., Loew, G. H., Bridges, A., and Waskell, L.
(1997) Protein Eng. 10, 119-129), was used to select amino acids predicted, by
computer docking studies and numerous previous biochemical and site-directed
mutagenesis studies, to be involved in binding the heme domain of cytochrome b5.
Twenty-four amino acid residues located on both the distal and the proximal
surface of the molecule were chosen for mutagenesis. These 24 mutant proteins
were expressed in Escherichia coli, purified, and characterized with respect to
their ability to bind cytochrome b5 and support substrate oxidation. Seven
mutants, R122A, R126A, R133A, F135A, M137A, K139A, and K433A, all on the proximal
surface of cytochrome P450 2B4 near the heme ligand, were identified that
exhibited decreased ability to bind cytochrome b5. All of the mutants except
K433A are located in either the C or C* helices or their termini. In addition,
these seven mutants and two additional mutants on the proximal surface of
cytochrome P450, R422A and R443A, were shown to exhibit decreased binding to
cytochrome P450 reductase. These studies indicate that the binding sites for
cytochrome b5 and cytochrome P450 reductase are, as predicted, located on the
proximal surface of cytochrome P450 2B4 and are partially overlapping but not
identical.
PMID- 9642269
TI - Full activation of the platelet-derived growth factor beta-receptor kinase
involves multiple events.
AB - Activation of receptor tyrosine kinases is thought to involve ligand-induced
dimerization, which promotes receptor transphosphorylation and thereby increases
the receptor's phosphotransferase activity. We used two platelet-derived growth
factor beta-receptor (beta-PDGFR) mutants to identify events that are required
for full engagement (autophosphorylation and activation of the kinase activity)
of the beta-PDGFR kinase. The F79/81 receptor (Tyr to Phe substitution at 579 and
581 in the juxtamembrane domain of the receptor) was capable of only very modest
ligand-dependent autophosphorylation and also failed to associate with numerous
SH2 domain-containing proteins. Furthermore, stimulation with platelet-derived
growth factor (PDGF) did not increase the kinase activity of the F79/81 mutant
toward exogenous substrates. However, the F79/81 receptor had basal kinase
activity and could be artificially stimulated by incubation with ATP. Because the
low kinase activity of the F857 mutant (Tyr to Phe substitution at 857 in the
putative activation loop) could not be increased by incubation with ATP, failure
to phosphorylate Tyr-857 may be the reason why the F79/81 mutant has low kinase
activity. Surprisingly, the F857 mutant underwent efficient PDGF-dependent
autophosphorylation. Thus the PDGF-dependent increase in the kinase activity of
the receptor is not required for autophosphorylation. We conclude that full
activation of the beta-PDGFR kinase requires at least two, apparently distinct
events.
PMID- 9642270
TI - Distinct saturable pathways for the endocytosis of different tyrosine motifs.
AB - Endocytosis of surface proteins through clathrin-coated pits requires an
internalization signal in the cytoplasmic domain. Two types of internalization
signal have been described: one requiring a tyrosine as the critical residue
(tyrosine-based motif), and the other consisting of either two consecutive
leucines or an isoleucine and leucine (dileucine motif). Although it seems that
these signals are necessary and sufficient for endocytic targeting, the mechanism
of recognition is not well understood. To examine this question, tetracycline
repressible cell lines were used to overexpress one of several receptors bearing
a tyrosine-based internalization signal. By measuring the rates of endocytosis
for either the overexpressed receptor, or that of other endogenous receptors, we
were able to show that the endocytosis of identical receptors could be saturated,
but a complete lack of competition exists between the transferrin receptor (TfR),
the low-density lipoprotein receptor, and the epidermal growth factor receptor.
Overexpression of any one of these receptors resulted in its redistribution
toward the cell surface, implying that entry into coated pits is limited. During
high levels of TfR expression, however, a significant increase in the amount of
surface Lamp1, but not low-density lipoprotein receptor, epidermal growth factor
receptor, or Lamp2, is detected. This suggests that Lamp1 and TfR compete for the
same endocytic sites. Together, these results support the idea that there are at
least three distinct saturable components involved in clathrin-mediated
endocytosis.
PMID- 9642271
TI - Inhibition of glucose trimming with castanospermine reduces calnexin association
and promotes proteasome degradation of the alpha-subunit of the nicotinic
acetylcholine receptor.
AB - To identify factors involved in the expression of ligand-gated ion channels, we
expressed nicotinic acetylcholine receptors in HEK cells to characterize roles
for oligosaccharide trimming, calnexin association, and targeting to the
proteasome. The homologous subunits of the acetylcholine receptor traverse the
membrane four times, contain at least one oligosaccharide, and are retained in
the endoplasmic reticulum until completely assembled into the circular
arrangement of subunits of delta-alpha-gamma-alpha-beta to enclose the ion
channel. We previously demonstrated that calnexin is associated with unassembled
subunits of the receptor, but appears to dissociate when subunits are assembled
in various combinations. We used the glucosidase inhibitor castanospermine to
block oligosaccharide processing, and thereby inhibit calnexin's interaction with
the oligosaccharides in the receptor subunits. Castanospermine treatment reduces
the association of calnexin with the alpha-subunit of the receptor, and
diminishes the intracellular accumulation of unassembled receptor subunit
protein. However, treatment with castanospermine does not appear to alter subunit
folding or assembly. In contrast, co-treatment with proteasome inhibitors and
castanospermine enhances the accumulation of polyubiquitin-conjugated alpha
subunits, and generally reverses the castanospermine induced loss of alpha
subunit protein. Co-transfection of cDNAs encoding the alpha- and delta-subunits,
which leads to the expression of assembled alpha- and delta- subunits, also
inhibits the loss of alpha-subunits expressed in the presence of castanospermine.
Taken together, these observations indicate that calnexin association reduces the
degradation of unassembled receptor subunits in the ubiquitin-proteasome pathway.
PMID- 9642272
TI - Functional defects of a muscle-specific calpain, p94, caused by mutations
associated with limb-girdle muscular dystrophy type 2A.
AB - p94 (calpain3), a muscle-specific member of the calpain family, has been shown to
be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A), a form of
autosomal recessive and progressive neuromuscular disorder. To elucidate the
molecular mechanism of LGMD2A, we constructed nine p94 missense point mutants
found in LGMD2A and analyzed their p94 unique properties. All mutants completely
or almost completely lose the proteolytic activity against a potential substrate,
fodrin. However, some of the mutants still possess autolytic activity and/or
connectin/titin binding ability, indicating these properties are not necessary
for the LGMD2A phenotypes. These results provide strong evidence that LGMD2A
results from the loss of proteolysis of substrates by p94, suggesting a novel
molecular mechanism leading to muscular dystrophies.
PMID- 9642273
TI - Identification of a novel bone morphogenetic protein-responsive gene that may
function as a noncoding RNA.
AB - Bone morphogenetic proteins (BMPs)/osteogenic proteins (OPs), members of the
transforming growth factor-beta superfamily, have a wide variety of effects on
many cell types including osteoblasts and chondroblasts, and play critical roles
in embryonic development. BMPs transduce their effects through binding to two
different types of serine/threonine kinase receptors, type I and type II.
Signaling by these receptors is mediated by the recently identified Smad
proteins. Despite the rapid progress in understanding of the signaling mechanism
downstream of BMP receptors, the target genes of BMPs are poorly understood in
mammals. Here we identified a novel gene, termed BMP/OP-responsive gene (BORG),
in C2C12 mouse myoblast cell line which trans-differentiates into osteoblastic
cells in response to BMPs. Expression of BORG was dramatically induced in C2C12
cells by the treatment with BMP-2 or OP-1 within 2 h and peaked at 12-24 h,
whereas transforming growth factor-beta had a minimal effect. BMP-dependent
expression of BORG was also detected in other cell types which are known to
respond to BMPs, suggesting that BORG is a common target gene of BMPs. Cloning
and sequence analysis of BORG cDNA and the genomic clones revealed that,
unexpectedly, the transcript of BORG lacks any extensive open reading frames and
contains a cluster of multiple interspersed repetitive sequences in its middle
part. The unusual structural features suggested that BORG may function as a
noncoding RNA, although it is spliced and polyadenylated as authentic protein
coding mRNAs. Together with the observation that transfection of antisense
oligonucleotides of BORG partially inhibited BMP-induced differentiation in C2C12
cells, it is possible that a new class of RNA molecules may have certain roles in
the differentiation process induced by BMPs.
PMID- 9642274
TI - Five discrete cis-active domains direct cell type-specific transcription of the
vasoactive intestinal peptide (VIP) gene.
AB - Vasoactive intestinal peptide (VIP) is a neuromodulator expressed with great
anatomical specificity throughout the nervous system. Cell-specific expression of
the VIP gene is mediated by a tissue specifier element (TSE) located within a 2.7
kilobase (kb) region between -5.2 and -2.5 kb upstream from the transcription
start site, and requires an intact promoter proximal VIP-CRE (cyclic AMP
responsive element) (Hahm, S. H., and Eiden, L. E. (1997) J. Neurochem. 67, 1872
1881). We now report that the TSE comprises a 425-base pair domain located
between -4.7 and -4.2 kb containing two AT-rich octamer-like sequences. The 425
base pair TSE is sufficient to provide full cell-specific regulation of the VIP
gene, when fused to the 5' proximal 1.55 kb of the VIP gene. Mutational analysis
and gel shift assays of these octamer-like sequences indicate that the binding of
proteins related to the ubiquitously expressed POU-homeodomain proteins Oct-1
and/or Oct-2 to these octamer-like sequences plays a central role for the
function of the TSE. The TSE interacts with three additional discrete domains
besides the cAMP response element, which are located within the proximal 1.55 kb
of the VIP gene, to provide cell-specific expression. An upstream domain from
1.55 to -1.37 kb contains E-boxes and MEF2-like motifs, and deletion of this
domain results in complete abrogation of cell-specific transcriptional activity.
The region from -1.37 to -1. 28 kb contains a STAT motif, and further removal of
this domain allows the upstream TSE to act as an enhancer in both SH-EP and HeLa
cells. The sequence from -1.28 to -0.9 kb containing a non-canonical AP-1 binding
sequence (Symes, A., Gearan, T., Eby, J., and Fink, J. S. (1997) J. Biol. Chem.
272, 9648-9654), is absolutely required for TSE-dependent cellspecific expression
of the VIP gene. Thus, five discrete domains of the VIP gene provide a
combination of enhancer and repressor activities, each completely contingent on
VIP gene context, that together result in cell-specific transcription of the VIP
gene.
PMID- 9642275
TI - Cell cycle- and chromatin binding state-dependent phosphorylation of human MCM
heterohexameric complexes. A role for cdc2 kinase.
AB - The mammalian MCM protein family, presently with six members, exists in the
nuclei in two forms, chromatin-bound and unbound. The former dissociates from
chromatin with progression through the S phase. Recently, we have established a
procedure to isolate chromatin-bound and unbound complexes containing all six
human MCM (hMCM) proteins by immunoprecipitation. In the present study, we
applied this procedure to HeLa cells synchronized in each of the G1, S, and G2/M
phases and could detect hMCM heterohexameric complexes in all three. In addition,
depending on the cell cycle and the state of chromatin association, hMCM2 and 4
in the complexes were found to variously change their phosphorylation states.
Concentrating attention on G2/M phase hyperphosphorylation, we found hMCM2 and 4
in the complexes to be good substrates for cdc2/cyclin B in vitro. Furthermore,
when cdc2 kinase was inactivated in temperature-sensitive mutant murine FT210
cells, the G2/M hyperphosphorylation of the murine MCM2 and MCM4 and release of
the MCMs from chromatin in the G2 phase were severely impaired. Taken together,
the data suggest that the six mammalian MCM proteins function and undergo cell
cycle-dependent regulation as heterohexameric complexes and that phosphorylation
of the complexes by cdc2 kinase may be one of mechanisms negatively regulating
the MCM complex-chromatin association.
PMID- 9642276
TI - Caspases cleave focal adhesion kinase during apoptosis to generate a FRNK-like
polypeptide.
AB - Focal adhesion kinase (Fak) is a non-receptor protein-tyrosine kinase that
stimulates cell spreading and motility by promoting the formation of contact
sites between the cell and the extracellular matrix (focal adhesions). It
suppresses apoptosis by transducing survival signals that emanate from focal
adhesions via the clustering of transmembrane integrins by components of the
extracellular matrix. We demonstrate that Fak is cleaved by caspases at two
distinct sites during apoptosis. The sites were mapped to DQTD772, which was
preferentially cleaved by caspase-3, and VSWD704, which was preferentially
cleaved by caspase-6 and cytotoxic T lymphocyte-derived granzyme B. The cleavage
of Fak during apoptosis separates the tyrosine kinase domain from the focal
adhesion targeting (FAT) domain. The carboxyl-terminal fragments that are
generated suppress phosphorylation of endogenous Fak and thus resemble a natural
variant of Fak, FRNK, that inhibits Fak activity by preventing the localization
of Fak to focal adhesions. The cleavage of Fak by caspases may thus play an
important role in the execution of the suicide program by disabling the anti
apoptotic function of Fak. Interestingly, rodent Fak lacks an optimal caspase-3
consensus cleavage site although it is cleaved in murine cells undergoing
apoptosis at an upstream site. This appears to be the first example of a caspase
substrate where the cleavage sites are not conserved between species.
PMID- 9642277
TI - The amino-terminal domain of human STAT4. Overproduction, purification, and
biophysical characterization.
AB - The multifunctional signal transducer and activator of transcription (STAT)
proteins relay signals from the cell membrane to the nucleus in response to
cytokines and growth factors. STAT4 becomes activated when cells are treated with
interleukin-12, a key cytokine regulator of cell-mediated immunity. Upon
activation, dimers of STAT4 bind cooperatively to tandem interferon-gamma
activation sequences (GAS elements) near the interferon-gamma gene and stimulate
its transcription. The amino-terminal domain of STAT4 (STAT4(1-124)) is required
for cooperative binding interactions between STAT4 dimers and activation of
interferon-gamma transcription in response to interleukin-12. We have
overproduced this domain of human STAT4 (hSTAT4(1-124)) in Escherichia coli and
purified it to homogeneity for structural studies. The circular dichroism
spectrum of hSTAT4(1-124) indicates that it has a well ordered conformation in
solution. The translational diffusion constant of hSTAT4(1-124) was determined by
nuclear magnetic resonance methods and found to be consistent with that of a
dimer. The rotational correlation time (tauc) of hSTAT4(1-124) was estimated from
15N relaxation to be 16 ns; this value is consistent with a 29-kDa dimeric
protein. These results, together with the number of signals observed in the two
dimensional 1H-15N heteronuclear single quantum coherence spectrum of uniformly
15N-labeled protein, indicate that hSTAT4(1-124) forms a stable, symmetric
homodimer in solution. Cooperativity in native STAT4 probably results from a
similar or identical interaction between the amino-terminal domains of adjacent
dimers bound to DNA.
PMID- 9642278
TI - Phosphatidylinositol 4-phosphate synthesis in immunoisolated caveolae-like
vesicles and low buoyant density non-caveolar membranes.
AB - This study examined phosphatidylinositol 4-phosphate (PtdIns4P) synthesis in
caveolae that have been suggested to be discrete signaling microdomains of the
plasma membrane and are enriched in the marker protein caveolin. Caveolin-rich
light membranes (CLMs) were isolated from A431 cells by detergent-free,
discontinuous density-gradient centrifugation method. The CLM fraction was
separated from the bulk of the cellular protein and was greatly enriched in
PtdIns, PtdIns4P, and phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) and
an adenosine-sensitive type II PtdIns 4-kinase activity. Preparation of CLMs by
an OptiPrep-based cell fractionation procedure confirmed the co-localization of
PtdIns 4-kinase and caveolin. Electron microscopy confirmed that an anti-caveolin
antiserum immunopurified vesicles from CLMs that were within the size range
described for caveolae in other systems. Co-immunoprecipitated PtdIns 4-kinase
activity could utilize endogenous PtdIns, present within the caveolae-like
vesicles, to produce PtdIns4P. The addition of recombinant phosphatidylinositol
transfer protein increased PtdIns 4-kinase activity both in immunoisolated
caveolae and CLMs. However, less than 1% of the total cellular PtdIns and PtdIns
4-kinase activity was present in caveolae-like vesicles, indicating that non
caveolar light membrane rafts are the main site for cellular PtdIns4P production.
PMID- 9642279
TI - The fragile-X-related gene FXR1 is a human autoantigen processed during
apoptosis.
AB - We describe a new human autoimmune antigen in a patient suffering from
scleroderma with high levels of antibodies to nucleolus and cytoplasmic antigens.
Using a Chinese hamster ovary cell expression library, we have shown that this
antigen corresponds to the autosomal Fragile-X-related gene FXR1. The deduced
amino acid sequence from the hamster cDNA is 97, 98, and 58% homologous to the
human, mouse, and Xenopus laevis FXR1 genes, respectively. Expression of the
hamster cDNA clone in Escherichia coli and antibody production indicates
unequivocally the location of the FXR1 protein in the cytoplasm of hamster cells.
Affinity chromatography followed by immunofluorescence microscopy analysis and
immunoblots demonstrated the presence of autoimmune IgGs to FXR1 in the
scleroderma patient. Immunolabeling studies in Jurkat cells, induced to apoptosis
by anti-Fas/APO1 serum, indicated that the FXR1 antigens were clearly displaced
from their original cytoplasmic location to several punctuated foci, resembling
the bleb-like membranous structures characteristic of cells at certain stages of
apoptosis. This phenomenon could be part of a putative mechanism in which the
FXR1 protein is presented as a target for the autoimmune response in humans.
PMID- 9642280
TI - Colony-stimulating factor-1 stimulates the formation of multimeric cytosolic
complexes of signaling proteins and cytoskeletal components in macrophages.
AB - Stimulation of macrophages with colony-stimulating factor-1 (CSF-1) results in
the protein tyrosine phosphorylation of the CSF-1 receptor (CSF-1R) and many
other, primarily cytosolic, proteins. Stimulation by CSF-1 at 4 degreesC was used
to facilitate the purification and identification of the proteins of the
cytosolic anti-phosphotyrosine (PY)-reactive fraction (alphaPY-RF) involved in
downstream signaling pathways. Confocal microscopy revealed that the PY proteins
are in close proximity to the CSF-1R at the plasma membrane. The alphaPY-RF
contained pre-existing complexes of PY proteins and non-PY proteins which
generally increased in size and PY protein content following CSF-1 stimulation.
PY proteins identified by microsequencing and Western blotting include Cbl,
STAT3, STAT5a, STAT5b, SHP-1, Shc, and two novel proteins pp57 and pp37. Other
proteins included cytoskeletal/contractile proteins (paxillin, vimentin,
elongation factor-1alpha, F-actin, tropomyosin, and myosin regulatory light
chain), Ras family signaling proteins (p85 (phosphoinositide 3-kinase), Vav, Ras
GTPase-activating protein SH3 domain-binding protein, and Grb2), DnaJ-like
protein, and glyceraldehyde-3-phosphate dehydrogenase. CSF-1 induced the de novo
recruitment of Cbl, STAT3, STAT5a, STAT5b, p85, SHP-1, Shc, vimentin, and Grb2 to
complexes and caused pre-existing complexes involving Vav, elongation factor
1alpha, and F-actin to increase in size. These studies indicate that CSF-1
induced protein tyrosine phosphorylation is associated with the reorganization of
complexes of cytoskeletal, signaling, and other proteins that mediate CSF-1
regulated motility and growth.
PMID- 9642281
TI - Estrogen response elements can mediate agonist activity of anti-estrogens in
human endometrial Ishikawa cells.
AB - Anti-estrogens like hydroxytamoxifen (OHT) have mixed agonist/antagonist
activities, leading to tissue-specific stimulation of cellular proliferation.
Partial agonist activity of OHT can be observed in vitro in endometrial carcinoma
cells like Ishikawa. Here, we have compared several anti-estrogens (including
extensively characterized OHT and pure anti-estrogens such as ICI164, 384 and
RU58,668, which are devoid of uterotrophic activity) for their capacity to
stimulate promoters containing estrogen response elements (EREs) or AP1-binding
sites (12-O-tetradecanoylphorbol-13-acetate response elements, TREs), the two
types of DNA motifs known to mediate transcriptional stimulation by estrogen
receptors. Assays were performed in Ishikawa cells either by transient
transfection or by using cell lines with stably propagated reporter vectors. In
transient transfection experiments, none of the anti-estrogens displayed agonist
activity on the promoters tested. In contrast, significant transcriptional
stimulation was observed with low concentrations of OHT and RU39,411 in Ishikawa
cells stably propagating reporter constructs containing a minimal ERE3-TATA
promoter. In addition, micromolar concentrations of OHT, but not of RU39,411,
stimulated stably propagated AP1-responsive reporter constructs. No
transcriptional stimulation of ERE- or TRE-containing promoters was observed with
the pure anti-estrogens ICI164,384 and RU58,668. These results indicate that the
presence of estrogen response elements in promoters is sufficient to mediate cell
specific agonism of anti-estrogens at the transcriptional level, and that
stimulation of AP1 activity may be restricted to a subset of anti-estrogens
possessing agonist activity on EREs. In addition, our results suggest that
transient transfections do not fully recapitulate in vivo conditions required to
observe agonist activity of anti-estrogens.
PMID- 9642282
TI - Heat shock protein 72 modulates pathways of stress-induced apoptosis.
AB - The resistance to stress-induced apoptosis conferred by the thermotolerant state
or by exogenous expression of HSP72 was measured in mouse embryo fibroblasts. The
induction of thermotolerance protects cells from heat, tumor necrosis factor
alpha (TNFalpha), and ceramide-induced apoptosis but not from ionizing radiation.
Because the development of thermotolerance is associated with increased levels of
heat shock proteins, we determined whether constitutive expression of one of the
major inducible heat shock proteins, HSP72, could also protect cells from stress
induced apoptosis. Cells expressing constitutive HSP72 were shown to have
significantly reduced levels of apoptosis after heat, TNFalpha, and ceramide but
not after ionizing radiation. Activation of stress-activated protein kinase/c-Jun
N-terminal kinase (SAPK/JNK) was found to be strongly inhibited in thermotolerant
cells after heat shock but not after other stresses. Cells that constitutively
express HSP72 did not demonstrate decreased SAPK/JNK activation after any of
these stresses. Thus, factors other than HSP72 that are induced in the
thermotolerant state are able to reduce activation of SAPK/JNK after heat stress.
Notably, the level of activation of SAPK/JNK did not correlate with the amount of
apoptosis detected after different stresses. Constitutive HSP72 expression
inhibited poly(ADP-ribose) polymerase cleavage in cells after heat shock and
TNFalpha but not after ceramide or ionizing radiation. The results suggest either
that SAPK/JNK activation is not required for apoptosis in mouse embryo
fibroblasts or that HSP72 acts downstream of SAPK/JNK. Furthermore, the data
support the concept that caspase activity, which can be down-regulated by HSP72,
is a crucial step in stress-induced apoptosis. Based on data presented here and
elsewhere, we propose that the heat shock protein family can be classified as a
class of anti-apoptotic genes, in addition to the Bcl-2 and inhibitor of
apoptosis protein families of genes.
PMID- 9642283
TI - In vitro reconstitution of the recombinant photosystem II light-harvesting
complex CP24 and its spectroscopic characterization.
AB - The light-harvesting chlorophyll a/b protein CP24, a minor subunit of the
photosystem II antenna system, is a major violaxanthin-binding protein involved
in the regulation of excited state concentration of chlorophyll a. This subunit
is poorly characterized due to the difficulty in isolation and instability during
purification procedures. We have used an alternative approach in order to gain
information on the properties of this protein; the Lhcb6 cDNA has been
overexpressed in bacteria in order to obtain the CP24 apoprotein, which was then
reconstituted in vitro with xanthophylls, chlorophyll a, and chlorophyll b,
yielding a pigment-protein complex with properties essentially identical to the
native protein extracted from maize thylakoids. Although all carotenoids were
supplied during refolding, the recombinant holoprotein exhibited high selectivity
in xanthophyll binding by coordinating violaxanthin and lutein but not neoxanthin
or beta-carotene. Each monomer bound a total of 10 chlorophyll a plus chlorophyll
b and two xanthophyll molecules. Moreover, the protein could be refolded in the
presence of different chlorophyll a to chlorophyll b ratios for yielding a family
of recombinant proteins with different chlorophyll a/b ratios but still binding
the same total number of porphyrins. A peculiar feature of CP24 was its refolding
capability in the absence of lutein, contrary to the case of other homologous
proteins, thus showing higher plasticity in xanthophyll binding. These
characteristics of CP24 are discussed with respect to its role in binding
zeaxanthin in high light stress conditions. The spectroscopic analysis of a
recombinant CP24 complex binding eight chlorophyll b molecules and a single
chlorophyll a molecule by Gaussian deconvolution allowed the identification of
four subbands peaking at wavelengths of 638, 645, 653, and 659 nm, which have an
increased amplitude with respect to the native complex and therefore identify the
chlorophyll b absorption in the antenna protein environment. Gaussian subbands at
wavelengths 666, 673, 679, and 686 nm are depleted in the high chlorophyll b
complex, thus suggesting they derive from chlorophyll a.
PMID- 9642284
TI - Regulation of a TATA-binding protein-associated factor during cellular
differentiation.
AB - RNA polymerase III transcription is down-regulated when F9 embryonal carcinoma
cells differentiate into parietal endoderm. This reflects a decrease in the
activity of TFIIIB, a multisubunit complex that is required for all class III
gene expression. Two essential components of TFIIIB are the TATA-binding protein
(TBP) and an associated polypeptide called BRF that is specific to this complex.
The abundance of both TBP and BRF decreases during F9 cell differentiation.
Whereas the amount of TBP assembled into TFIIIB is down-regulated, this is not
the case for all TBP-containing complexes. BRF levels show a more dramatic
decline that appears sufficient to account for the overall change in
transcriptional activity. Developmental regulation of a specific class of genes
may therefore be achieved through changes in the availability of a TBP-associated
factor.
PMID- 9642285
TI - The human interferon-inducible protein, IFI 16, is a repressor of transcription.
AB - IFI 16 is a member of a family of interferon-inducible proteins, including the
human MNDA (myeloid nuclear differentiation antigen), the recently identified AIM
2 (absent in melanoma), and the homologous murine molecules, p202, p204, and D3.
IFI 16 contains a domain at the amino terminus capable of binding double-stranded
DNA and a bipartite nuclear localization signal. No molecular or biological
function has been assigned to any of the human family members, although a role in
transcription regulation has been proposed. In the present study, we show IFI 16
fused to the GAL4 DNA binding domain can function as a transcriptional repressor.
IFI 16-mediated repression is not dependent on the position or distance of IFI 16
binding, relative to the site of transcription initiation, and it can
significantly repress when only one GAL4 DNA element is present in the promoter.
We mapped the transcriptional repression domains to the 200 amino acid repeat
regions common to all human and mouse family members. We also demonstrate that
wild type IFI 16 can repress transcription of a reporter gene containing the
minimal promoter region of the human cytomegalovirus UL54 gene. Thus, IFI 16 is a
transcriptional repressor, with a modular structure typical of many known
transcription regulators.
PMID- 9642286
TI - Arrangement of the multicopy H+-translocating subunit c in the membrane sector of
the Escherichia coli F1F0 ATP synthase.
AB - The multicopy subunit c of the H+-transporting F1F0 ATP synthase of Escherichia
coli is thought to fold across the membrane as a hairpin of two hydrophobic alpha
helices. The conserved Asp61, centered in the second transmembrane helix, is
essential for H+ transport. In this study, we have made sequential Cys
substitutions across both transmembrane helices and used disulfide cross-link
formation to determine the oligomeric arrangement of the c subunits. Cross-link
formation between single Cys substitutions in helix 1 provided initial
limitations on how the subunits could be arranged. Double Cys substitutions at
positions 14/16, 16/18, and 21/23 in helix 1 and 70/72 in helix 2 led to the
formation of cross-linked multimers upon oxidation. Double Cys substitutions in
helix 1 and helix 2, at residues 14/72, 21/65, and 20/66, respectively, also
formed cross-linked multimers. These results indicate that at least 10 and
probably 12 subunits c interact in a front-to-back fashion to form a ring-like
arrangement in F0. Helix 1 packs at the interior and helix 2 at the periphery of
the ring. The model indicates that the Asp61 carboxylate is centered between the
helical faces of adjacent subunit c at the center of a four-helix bundle.
PMID- 9642287
TI - Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth
factor receptor.
AB - CrkII adaptor protein becomes tyrosine-phosphorylated upon various types of
stimulation. We examined whether tyrosine 221, which has been shown to be
phosphorylated by c-Abl, was phosphorylated also by other tyrosine kinases, such
as epidermal growth factor (EGF) receptor. For this purpose, we developed an
antibody that specifically recognizes Tyr221-phosphorylated CrkII, and we
demonstrated that CrkII was phosphorylated on Tyr221 upon EGF stimulation. When
NRK cells were stimulated with EGF, the tyrosine-phosphorylated CrkII was
detected at the periphery of the cells, where ruffling is prominent, suggesting
that signaling to CrkII may be involved in EGF-dependent cytoskeletal
reorganization. The EGF-dependent phosphorylation of CrkII was also detected in a
c-Abl-deficient cell line. Moreover, recombinant CrkII protein was phosphorylated
in vitro by EGF receptor. These results strongly suggest that EGF receptor
directly phosphorylates CrkII. Mutational analysis revealed that the src homology
2 domain was essential for the phosphorylation of CrkII by EGF receptor but not
by c-Abl, arguing that these kinases phosphorylate CrkII by different
phosphorylation mechanisms. Finally, we found that the CrkII protein
phosphorylated upon EGF stimulation did not bind to the phosphotyrosine
containing peptide and that CrkII initiated dissociation from EGF receptor within
3 min even with the sustained tyrosine phosphorylation of EGF receptor. This
result implicated phosphorylation of Tyr221 in the negative regulation of the src
homology 2-mediated binding of CrkII to EGF receptor.
PMID- 9642288
TI - Porcine spleen deoxyribonuclease II. Covalent structure, cDNA sequence, molecular
cloning, and gene expression.
AB - Porcine spleen DNase II, a lysosomal acid hydrolase, is a noncovalently linked
alpha.beta heterodimer (Liao, T.-H. (1985) J. Biol. Chem. 260, 10708-10713). The
alpha subunit, after disulfide cleavage, yields two chains, alpha1 and alpha2.
The complete amino acid sequences of the alpha1, beta, and alpha2 chains were
elucidated by protein sequencing, and the pairings of one interchain disulfide
between alpha1 and alpha2 and of three intrachain disulfides in alpha2 were
assigned. Six carbohydrate attachment sites, two in beta and four in alpha2, were
detected by sugar analyses. The cDNA of DNase II was amplified using primers
synthesized on the basis of the amino acid sequences determined. The amplified
fragments shown to be a cDNA sequence of 1,292 bases. This cDNA sequence has an
open reading frame encoding a 364-amino acid polypeptide containing a putative
transmembrane peptide at the NH2-end, two small connecting peptides in the
middle, and a peptide at the COOH terminus. These are evidently removed to form
mature DNase II. Thus, all three chains in the sequence alpha1, beta, and alpha2
are coded by the same cDNA. When Chinese hamster ovary cells were transfected
with a cloned plasmid with an inserted cDNA fragment encoding the entire reading
frame, the expressed protein was released into the growth medium as an active
form of DNase II.
PMID- 9642289
TI - Genetic evidence that phosphatidylserine synthase II catalyzes the conversion of
phosphatidylethanolamine to phosphatidylserine in Chinese hamster ovary cells.
AB - Phosphatidylserine (PS) in mammalian cells is synthesized through the exchange of
free L-serine with the base moiety of phosphatidylcholine or
phosphatidylethanolamine (PE). The serine base exchange in Chinese hamster ovary
(CHO) cells is catalyzed by at least two enzymes, PS synthase (PSS) I and II. A
PSS I-lacking mutant of CHO-K1 cells, PSA-3, which exhibits approximately 2-fold
lower serine base exchange activity than CHO-K1, is defective in the conversion
of phosphatidylcholine to PS but has the ability to convert PE to PS. The PSA-3
mutant requires exogenous PS or PE for cell growth. In the present study, from
PSA-3 mutant cells, we isolated a mutant, named PSB-2, with a further decrease in
the serine base exchange activity. The activity in the homogenate of PSB-2 mutant
cells was approximately 10% that of PSA-3 mutant cells and approximately 5% that
of CHO-K1 cells. The PSB-2 mutant exhibited an approximately 80% reduction in the
PSS II mRNA level relative to that in PSA-3 mutant and CHO-K1 cells. These
results showed that the PSB-2 mutant is defective in PSS II. Like the PSA-3
mutant, the PSB-2 mutant grew well in medium supplemented with PS. However, in
the medium supplemented with PE, the PSB-2 mutant was incapable of growth, in
contrast to the PSA-3 mutant. In the medium with exogenous PE, the PSB-2 mutant
was defective in PS biosynthesis, whereas the PSA-3 mutant synthesized a normal
amount of PS. A metabolic labeling experiment with exogenous [32P]PE revealed
that the PSB-2 mutant was defective in the conversion of exogenous PE to PS. This
defect and the growth and PS biosynthetic defects of the PSB-2 mutant cultivated
with exogenous PE were complemented by the PSS II cDNA. In addition, the cDNA of
the other PS synthase, PSS I, was shown not to complement the defect in the
conversion of exogenous PE to PS of the PSB-2 mutant, implying that PSS I
negligibly contributes to the conversion of PE to PS in CHO-K1 cells. These
results indicated that PSS II is critical for the growth and PS biosynthesis of
PSA-3 mutant cells cultivated with exogenous PE and suggested that most of the PS
formation from PE in CHO-K1 cells is catalyzed by PSS II.
PMID- 9642290
TI - Regulation of expression within a gene family. The case of the rat gammaB- and
gammaD-crystallin promoters.
AB - The six closely related and clustered rat gamma-crystallin genes, the gammaA- to
gammaF-crystallin genes, are simultaneously activated in the embryonic lens but
differentially shut down during postnatal development with the gammaB-crystallin
gene, the last one to be active. We show here that developmental silencing of the
gammaD-crystallin promoter correlates with delayed demethylation during lens
fiber cell differentiation. Methylation silencing of the gammaD-crystallin
promoter is a general effect and does not require the methylation of a specific
CpG, nor does methylation interfere with factor binding to the proximal
activator. In later development, the gammaD-crystallin promoter is also shut down
earlier by a repressor that footprints to the -91/-78 region. A factor with
identical properties is present in brain. Hence, a ubiquitous factor has been
recruited as a developmental regulator by the lens. All gamma-crystallin
promoters tested contain upstream silencers, but at least the gammaB-crystallin
silencer is distinct from the gammaD-crystallin silencer. The gamma-crystallin
promoters were found to share a proximal activator (the gamma-box; around -50),
which behaves as a MARE. The gammaB-box is recognized with much lower avidity
than the gammaD-box. By swapping elements between the gammaB- and the gammaD
crystallin promoter, we show that activation by the gammaB-box requires a
directly adjacent -46/-38 AP-1 consensus site. These experiments also uncovered
another positive element in the gammaD-crystallin promoter, around -10. In the
context of the gammaD-crystallin promoter, this element is redundant; in the
context of the gammaB-crystallin promoter, it can replace the -46/-38 element.
PMID- 9642291
TI - A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific
adenines in single-stranded DNA.
AB - Although the biological function of DNA glycosylases is to protect the genome by
removal of potentially cytotoxic or mutagenic bases, this investigation describes
the existence of natural DNA glycosylases with activity on undamaged,
nonmispaired bases. Gelonin, pokeweed antiviral protein, and ricin, previously
described as ribosome-inactivating proteins, are shown to damage single-stranded
DNA by removal of a protein-specific set of adenines and cleavage at the
resulting abasic sites. Using an oligonucleotide as the substrate reveals that
the reaction proceeds via the enzyme-DNA imino intermediate characteristic of DNA
glycosylase/AP lyases. The adenine glycosylase activity on single-stranded DNA
reported here challenges the concept that a normal base has to be in a mismatch
to be specifically removed. By contrast to other glycosylases, these enzymes are
expected to damage DNA rather than participate in repair processes. The
significance of this DNase activity to the biological function of these plant
proteins and to their toxicity to animal cells remains to be determined.
PMID- 9642292
TI - Oligomeric nature of the integral membrane protein stomatin.
AB - The 31-kDa integral membrane protein stomatin (protein 7.2b) is not only an
important component of the red cell membrane but can also be found in abundance
in different tissues and cell lines. The protein is thought to be anchored to the
membrane by a hydrophobic domain while both N and C termini are exposed to the
cytoplasm. We have previously shown in the human cell line UAC that stomatin
concentrates preferentially in plasma membrane folds and protrusions. There is
also evidence that stomatin is linked to the cortical actin cytoskeleton,
suggesting a role in cortical morphogenesis of the cell. In this study, we
demonstrate that the fundamental structure of stomatin is oligomeric. Whereas
interaction of stomatin with itself was suggested by cross-linking experiments,
we show by density gradient centrifugation analysis that soluble homo-oligomeric
complexes of this protein are present in Triton X-100 extracts of UAC cells. We
also show the existence of these oligomers by co-immunoprecipitation of the
endogenous stomatin and a recombinantly expressed myc-tagged stomatin, using an
anti-myc antibody. The data indicate that these complexes comprise between 9 and
12 monomers of stomatin. Two C-terminally truncated forms of stomatin do not
incorporate into these oligomers, suggesting an involvement of the C terminus in
the homo-oligomeric interaction.
PMID- 9642293
TI - Conserved in vivo phosphorylation of calnexin at casein kinase II sites as well
as a protein kinase C/proline-directed kinase site.
AB - Calnexin is a lectin-like chaperone of the endoplasmic reticulum (ER) that
couples temporally and spatially N-linked oligosaccharide modifications with the
productive folding of newly synthesized glycoproteins. Calnexin was originally
identified as a major type I integral membrane protein substrate of kinase(s)
associated with the ER. Casein kinase II (CK2) was subsequently identified as an
ER-associated kinase responsible for the in vitro phosphorylation of calnexin in
microsomes (Ou, W-J., Thomas, D. Y., Bell, A. W., and Bergeron, J. J. M. (1992)
J. Biol. Chem. 267, 23789-23796). We now report on the in vivo sites of calnexin
phosphorylation. After 32PO4 labeling of HepG2 and Madin-Darby canine kidney
cells, immunoprecipitated calnexin was phosphorylated exclusively on serine
residues. Using nonradiolabeled cells, we subjected calnexin immunoprecipitates
to in gel tryptic digestion followed by nanoelectrospray mass spectrometry
employing selective scans specific for detection of phosphorylated fragments.
Mass analyses identified three phosphorylated sites in calnexin from either HepG2
or Madin-Darby canine kidney cells. The three sites were localized to the more
carboxyl-terminal half of the cytosolic domain: S534DAE (CK2 motif), S544QEE (CK2
motif), and S563PR. We conclude that CK2 is a kinase that phosphorylates calnexin
in vivo as well as in microsomes in vitro. Another yet to be identified kinase
(protein kinase C and/or proline-directed kinase) is directed toward the most
COOH-terminal serine residue. Elucidation of the signaling cascade responsible
for calnexin phosphorylation at these sites in vivo may define a novel regulatory
function for calnexin in cargo folding and transport to the ER exit sites.
PMID- 9642294
TI - The effects of chaperones and the influence of protein assembly on peroxisomal
protein import.
AB - Peroxisomal proteins are synthesized in the cytoplasm and post-translationally
translocated into the organelle. The role of chaperones and protein folding in
peroxisomal protein transport is still unclear. Translocation of proteins into
mitochondria requires that precursor proteins assume an extended conformation;
cytosolic chaperones are thought to help maintain this conformation. In contrast,
peroxisomal protein import does not require unfolding of the targeted protein.
However, the molecular chaperones Hsp70 and Hsp40 may be important for
translocation. We present several lines of evidence that show that plant
peroxisomal protein import is enhanced by chaperones. First, peroxisomes isolated
from heat-shocked pumpkin seedling tissues exhibited increased protein import
relative to control peroxisomes. Second, antibodies raised against wheat germ
cytosolic Hsp70 and Escherichia coli Hsp90 inhibited import of the peroxisomal
protein isocitrate lyase. To our knowledge, this is the first time that Hsp90 has
been directly implicated in a protein transport event. Third, peroxisomal
proteins were immunoprecipitated by wheat germ Hsp70 antibodies. We also present
results that suggest that the efficiency of peroxisomal protein import is
influenced by the structure of the targeted protein; monomeric isocitrate lyase
was imported more efficiently than oligomeric isocitrate lyase. Taken together,
these data demonstrate that the assembly state of peroxisomal proteins and the
chaperones that may mediate those states are both important for efficient
peroxisomal protein import.
PMID- 9642295
TI - Topology of SREBP cleavage-activating protein, a polytopic membrane protein with
a sterol-sensing domain.
AB - The NH2-terminal fragments of sterol regulatory element-binding proteins (SREBPs)
are released from endoplasmic reticulum membranes by proteases whose activities
depend upon SREBP cleavage-activating protein (SCAP), a polytopic endoplasmic
reticulum membrane protein. The activity of SCAP is inhibited by sterols, which
appear to interact with the polytopic membrane domain of SCAP. Here, we use
protease protection and N-linked glycosylation site-mapping techniques to define
the topology of the eight membrane-spanning domains of SCAP. The data indicate
that the NH2 terminus and COOH terminus of SCAP face the cytosol. The long
intralumenal loops after membrane-spanning segments 1 and 7 are glycosylated,
confirming their lumenal location. The region comprising membrane-spanning
segments 2-6 shows sequence resemblance to putative sterol-sensing domains in
three other proteins: 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA
reductase), the Niemann-Pick C1 protein, and the morphogen receptor Patched. The
orientation of the eight membrane-spanning segments in SCAP is consistent with
the model proposed for HMG-CoA reductase (Olender, E. H., and Simoni, R. D.
(1992) J. Biol. Chem. 267, 4223-4235). The membrane-spanning domains of SCAP and
HMG-CoA reductase confer sterol sensitivity upon the functional activities of the
two molecules. The common membrane topology of the two proteins is consistent
with the notion that sterols regulate both proteins by a common mechanism.
PMID- 9642296
TI - Unique composition of the preprotein translocase of the outer mitochondrial
membrane from plants.
AB - Transport of most nuclear encoded mitochondrial proteins into mitochondria is
mediated by heteropolymeric translocases in the membranes of the organelles. The
translocase of the outer mitochondrial membrane (TOM) was characterized in fungi,
and it was shown that TOM from yeast comprises nine different subunits. This
publication is the first report on the preparation of the TOM complex from plant
mitochondria. The protein complex from potato was purified by (a) blue native
polyacrylamide gel electrophoresis and (b) by immunoaffinity chromatography. On
blue native gels, the potato TOM complex runs close to cytochrome c oxidase at
230 kDa and hence only comprises about half of the size of fungal TOM complexes.
Analysis of the TOM complex from potato by SDS-polyacrylamide gel electrophoresis
allows separation of seven different subunits of 70, 36, 23, 9, 8, 7, and 6 kDa.
The 23-kDa protein is identical to the previously characterized potato TOM20
receptor, as shown by in vitro assembly of this protein into the 230-kDa complex,
by immunoblotting and by direct protein sequencing. Partial amino acid sequence
data of the other subunits allowed us to identify sequence similarity between the
36-kDa protein and fungal TOM40. Sequence analysis of cDNAs encoding the 7-kDa
protein revealed significant sequence homology of this protein to TOM7 from
yeast. However, potato TOM7 has a N-terminal extension, which is very rich in
basic amino acids. Counterparts to the TOM22 and TOM37 proteins from yeast seem
to be absent in the potato TOM complex, whereas an additional low molecular mass
subunit occurs. Functional implications of these findings are discussed.
PMID- 9642297
TI - Cell surface ectodomain cleavage of human amphiregulin precursor is sensitive to
a metalloprotease inhibitor. Release of a predominant N-glycosylated 43-kDa
soluble form.
AB - Biosynthesis and processing of amphiregulin (AR) have been investigated in human
colorectal (HCA-7, Caco-2) and mammary (MCF-7) cancer cell lines, as well as in
Madin-Darby canine kidney cells stably expressing various human AR precursor (pro
AR) forms. Both cells expressing endogenous and transfected AR produce multiple
cellular and soluble forms of AR with an N-glycosylated 50-kDa pro-AR form being
predominant. Our results demonstrate that sequential proteolytic cleavage within
the ectodomain of the 50-kDa pro-AR form leads to release of a predominant N
glycosylated 43-kDa soluble AR, as well as the appearance of other cellular and
soluble AR forms. Cell surface biotinylation studies using a C-terminal epitope
tagged pro-AR indicate that all cell surface forms are membrane-anchored and
support that AR is released by ectodomain cleavage of pro-AR at the plasma
membrane. We also show that pro-AR ectodomain cleavage is a regulated process,
which can be stimulated by phorbol 12-myristate 13-acetate and inhibited by the
metalloprotease inhibitor, batimastat. In addition, we provide evidence that high
molecular mass AR forms may retain the full-length N-terminal pro-region, which
may influence the biological activities of these forms.
PMID- 9642298
TI - Rab2 protein enhances coatomer recruitment to pre-Golgi intermediates.
AB - The Rab2 protein is a resident of pre-Golgi intermediates and required for
vesicular transport in the early secretory pathway. We have previously shown that
a peptide corresponding to the amino terminus of Rab2 (residues 2-14) arrests
protein traffic prior to a rate-limiting event in VSV-G movement through pre
Golgi structures (Tisdale, E. J., and Balch, W. E. (1996) J. Biol. Chem. 271,
29372-29379). To determine the mechanism by which this peptide inhibits
transport, we investigated the effect of the Rab2 peptide on the distribution of
the beta-COP subunit of coatomer because COPI partially localizes to pre-Golgi
intermediates. We found that the peptide caused a dramatic change in the
distribution of pre-Golgi intermediates containing beta-COP. A quantitative
binding assay was employed to measure recruitment of beta-COP to membrane when
incubated with the Rab2 (13-mer). Peptide-treated microsomes showed a 25-70%
increase in the level of membrane-associated beta-COP. The enhanced recruitment
of coatomer to membrane was specific to the Rab2 (13-mer) and required guanosine
5'-3-O-(thio)triphosphate, ADP ribosylation factor, and protein kinase C-like
activity. The ability to enhance beta-COP membrane binding was not limited to the
peptide. Similarly, the addition of recombinant Rab2 protein to the assay
promoted beta-COP membrane association. Our results suggest that the Rab2 peptide
causes the persistent recruitment of COPI to pre-Golgi intermediates which
ultimately arrests protein transport due to the inability of membranes to uncoat.
PMID- 9642299
TI - Ribosome binding to mitochondria is regulated by GTP and the transit peptide.
AB - The association between ribosomes and the pore proteins at the endoplasmic
reticulum membrane is important to co-translational translocation. To determine
if a similar association occurs between the ribosome and mitochondrial membrane
protein(s) during protein import in higher eukaryotes, we examined ribosome
mitochondria binding. By using spectral measurements, analysis of mitochondrial
associated RNA, and electron microscopy, we demonstrated that ribosomes stably
bind to purified rat liver mitochondria in vitro. Binding of ribosomes to
mitochondria was markedly reduced by GTP and nearly abolished by the non
hydrolyzable GTP analogue, guanosine-5'-[thio]-triphosphate (GTPgammaS), but was
only modestly reduced by GDP or ATP and unaffected by CTP. The initial rate of
GTP hydrolysis by mitochondria was increased by ribosomes, whereas the rate of
ATP hydrolysis by mitochondria was not affected. Ribosomes programmed with mRNA
for 92 amino acids of the N terminus of mitochondrial malate dehydrogenase bound
to mitochondria, but unlike unprogrammed rat liver ribosomes, neither GTP nor GDP
disrupted binding; however, GTPgammaS did. These data show that receptors
specific for ribosomes are present on the mitochondrial membrane, and a GTP
dependent process mediates this binding. The presence of a nascent chain alters
these binding characteristics. These findings support the hypothesis that a co
translational translocation pathway exists for import of proteins into
mitochondria.
PMID- 9642300
TI - The gene encoding human nuclear protein tyrosine phosphatase, PRL-1. Cloning,
chromosomal localization, and identification of an intron enhancer.
AB - Expression of the rat PRL-1 gene, which encodes a unique nuclear protein tyrosine
phosphatase, is positively associated with cellular growth during liver
development, regeneration, and oncogenesis but with differentiation in intestine
and other tissues. Here, we analyzed the structure of the human PRL-1 gene and
localized it to chromosome 6 within band q12. Human, rat, and mouse PRL-1 are
100% conserved at the amino acid level and 55% identical to a newly identified
Caenorhabditis elegans PRL-1. The presence of two promoter activities, P1 and P2,
in the human PRL-1 gene were identified by primer extension and RNase protection
assays. A functional TATA box was identified in promoter P1 upstream of the non
coding first exon. A non-canonical internal promoter, P2, was found in the first
intron that results in PRL-1 transcripts beginning 8 base pairs downstream of the
5'-end of exon 2 and causes no alteration in the encoded protein. The first 200
base pair region of either promoter P1 or P2 conferred high basal transcriptional
activity. An enhancer that bound a developmentally regulated factor, PRL-1 intron
enhancer complex (PIEC), was localized to the first intron of the human PRL-1
gene. The presence of PIEC correlated with the ability of the intron enhancer to
confer transcriptional activation in HepG2 and F9 cells. The intron enhancer
contributed significantly to PRL-1 promoter activity in HepG2 cells which contain
PIEC but not to NIH 3T3 cells which do not.
PMID- 9642301
TI - New frontiers in physiology of presby-cardia.
PMID- 9642302
TI - The use of gonadotrophin-releasing hormone analogues in gynaecology.
PMID- 9642303
TI - Comparative study of effects of three kinds of herbal mixture decoctions on
improving immune senescence and free radical metabolism.
AB - OBJECTIVE: To verify from the aspects of immune senescence and free radical
metabolism that "removing blood stasis as well as tonifying kidney is an ideal
way to delay aging" and further investigate the anti-aging mechanism of this
therapy. METHODS: In the first period, the old mice were separately fed with the
herbal decoction of the recipe of tonifying kidney, or of removing blood stasis,
or of tonifying kidney and removing blood stasis for four weeks, and then IL-2
production of splenic lymphocytes, IL-1 production of peritoneal macrophages,
SOD, CAT and GSH-Px activity in erythrocytes, and LPO contents in liver and brain
were compared between the young control group and the old control group, or the
old control group and each of the old medication groups. In the second period,
the adult mice inhaled ozone or the splenic lymphocytes from adult mice were
cultured in the medium containing peroxide hydrogen. The effects of free radicals
on immune system and the reversion of the herbal decoction of the recipe of
removing blood stasis as well as tonifying kidney were observed. RESULTS: The
activities of IL-1, IL-2, SOD, CAT and GSH-PX in old mice were significantly
lower than those in young mice, and LPO contents were higher. The three herbal
decoctions all have reversing effects on each of these parameters except that the
decoction of removing blood stasis has inhibitory effects on IL-1 and IL-2
production. The effect of the decoction of removing blood stasis as well as
tonifying kidney was the best among the three decoctions, and it can also reverse
the impaired production of IL-2 by ozone in vivo and peroxide hydrogen in vitro.
CONCLUSIONS: The therapeutic method of removing blood stasis as well as tonifying
kidney is an ideal way to delay aging, and its effects to improve immune
senescence is correlated with the decrease of free radical damages.
PMID- 9642304
TI - Induction of c-fos/c-myc expression by epidermal growth factor decreases with
alteration of their gene binding proteins in senescent fibroblasts.
AB - OBJECTIVE: To observe the changes of proto-oncogene c-fos/c-myc expression and
its relation to specific transcription factors in human senescent fibroblast
after epidermal growth factor (EGF) addition. METHODS: The c-fos/c-myc expression
were analysed by Northern blot. Transcription factors were analysed by
Southwestern blot. RESULTS: (1) The expression of c-fos/c-myc was less
susceptible to induction by EGF as the cells aged. (2) EGF increased the binding
of protein P91 to c-fos with regulatory sequence and P80 to c-myc with regulatory
sequence, but the increased levels of both proteins were significantly reduced in
senescent cells. CONCLUSIONS: Inability of c-fos/c-myc gene induction by EGF in
senescent cells might be correlated with some DNA-binding proteins.
PMID- 9642305
TI - A study on rIL-4 and IFN-gamma regulating IgE synthesis in bronchial asthma
patients.
AB - OBJECTIVE: To investigate the cytokines responsible for pathophysiology of
asthma. METHODS: In vitro effects of recombinant interleukin-4 (rIL-4) and
interferon-gamma (IFN-gamma) on synthesis of immunoglobulin E (IgE) by peripheral
blood mononuclear cells (PBMC) were studied in 30 asthmatic patients and 25
normal controls. RESULTS: Spontaneous IgE synthesis by PBMC significantly
increased in patients with asthma compared with the controls (t = 4.471, P <
0.001). Although the maximum amounts of IgE synthesis using PBMC after
stimulation with rIL-4 were almost the same in the patients with asthma and in
the controls (P > 0.05), the enhancement rate of rIL-4-induced IgE synthesis was
lower in the asthma patients than in the controls (t = 4.6719, P > 0.005). IFN
gamma suppressed both spontaneous and rIL-4-induced IgE synthesis by PBMC in the
asthma patients. The suppressive effect on IgE synthesis was more prominent in
the patients with asthma than in the controls (t = 7.1833, P < 0.001).
CONCLUSIONS: Asthma attacks are related to IgE-dependent trigger mechanism. The
imbalance of IL-4 and IFN-gamma in vivo is the cause of elevated IgE than can
produce mediators release and asthma attacks. IFN-gamma can inhibit IgE
synthesis, so IFN-gamma may be a new approach to the treatment of asthma.
PMID- 9642306
TI - Primary structure and variability of partial nonstructural gene 5 region of
hepatitis G virus.
AB - OBJECTIVE: To sequence partial nonstructural 5 (NS5) gene of hepatitis G virus
(HGV) in the sera of Chinese patients with chronic non-A-E hepatitis or hepatitis
B virus (HBV) infection. METHODS: Total nucleic acid was extracted from the sera
of 35 patients with chronic non-A-E hepatitis and 20 patients with HBV infection,
then it was subjected to reverse transcriptase-nested-polymerase chain reaction
(RT-nested-PCR) with primers derived from the putative nonstructural gene 5 (NS5)
region of HGV. The positive PCR products (994 bp in length) were directly
sequenced using the Sang's method after purification. RESULTS: HGV RNA was
detected in 1 of the 35 patients (2.9%) with chronic non-A-E hepatitis and 5 of
the 20 patients (25%) with HBV infection. All the 6 positive samples were
sequenced. These 6 Chinese isolates exhibited 87.21% to 93.92% nucleotide
sequence identities with 3 reported isolates (GBV-C, PNF2161, R10292) over the
994 nucleotides examined, while the nucleotide homologies among the 6 isolates
were 90.09% to 93.82%. And 93.61% to 98.72% homologies were found at the deduced
amino acid level in comparing the 6 isolates with 3 reported ones, while 93.61%
to 98.40% amino acid identities were found among the 6 isolates. In the region
sequenced, there existed 16 conserved proline residues and 8 conserved cysteine
residues. CONCLUSIONS: Six isolates of HGV were obtained from different Chinese
patients in this study. The partial nucleotide sequences, as well as amino acid
sequences, of the putative NS5 region of HGV in Chinese patients are relatively
conserved. The overall degree of nucleotide conservation (90.09% to 93.82%) among
Chinese isolates may make this region of the genome suitable for the development
of diagnosis reagents.
PMID- 9642307
TI - Autoantibodies and anti-interferon antibody in patients with chronic viral
hepatitis and its clinical significance: a preliminary investigation.
AB - OBJECTIVE: To determine the antoantibodies and anti-interferon antibody in
chronic viral hepatitis patients treated with interferon and the relation of the
antibodies to the curative effect of interferon. METHODS: Forty chronic viral
hepatitis patients (twenty cases for hepatitis B; twenty patients for hepatitis
C) were studied. Indirect immunofluorescence assay (IFA) was used to measure the
autoantibodies. Enzyme immunoassay (EIA) was used to measure the anti-interferon
total antibody. RESULTS: Compared with normal groups, the autoantibodies in
patients increased significantly (P < 0.01), and the anti-interferon antibody in
chronic hepatitis B and hepatitis C patients had an obvious difference (P <
0.05). As for the curative effect, the presence or absence of autoantibodies did
not have a distinct significance in patients treated with alpha-interferon, but
the patients with anti-interferon antibody before or after therapy might have a
different response to alpha-interferon. CONCLUSIONS: It was suggested that the
presence of autoantibodies was not a contraindication to the use of interferon in
patients with chronic viral hepatitis; the clinical significance of anti
interferon antibody should be further studied.
PMID- 9642308
TI - Bridging nerve defects with differently treated muscle grafts: assessment of
microsphere technique for measurement of blood flow in rats.
AB - OBJECTIVE: To select advanced points from differently treated muscle grafts and
explore a new conduit to bridge nerve defects. METHODS: A total of 70 Sprague
Dawley rats were employed in this experiment. We applied a frozen probe to freeze
the muscle in situ to disrupt any cellular elements of the local muscle grafts,
but blood vessels to the muscle were carefully preserved. Radioactive microsphere
technique was employed to visualize the blood supply to the muscle grafts.
Immunohistochemical staining and ultrastructural observation were also carried
out to assess the results of nerve regeneration. RESULTS: The in-situ frozen
muscle grafts were revascularized within the first 3 days, which led to fast
migration of macrophages and Schwann cells. That was really reflected in the
final results: the early incursion of regenerating axons, more regenerating axons
at the early stage both in the grafts and distal stumps, and thicker myelin
sheath of regenerating axons. CONCLUSIONS: The in-situ frozen autogenous muscle
graft is useful in the repair of sciatic nerve of rats. In the thicker and longer
grafts the benefits will be more remarkable. It will be the most useful technique
for nerve repair, especially in the repair of a large nerve gap in a poor
recipient bed.
PMID- 9642309
TI - A new method for computerized tomography diagnosis of early transtentorial
hernia.
AB - OBJECTIVE: To evaluate a new scanning method designed for the diagnosis of early
transtentorial hernia as compared with the routine scanning method (parallel to
orbitomeatal line). METHODS: 102 patients with unilateral high intracranial
pressure and 100 volunteers without any cranial symptoms and signs were scanned
on (1) the plane perpendicular to the plane of clivus and (2) the plane parallel
to orbitomeatal line, a line joining the apex of the dorsum sellae and the lowest
point of the clivus. RESULTS: Vertical-to-clivus scanning method directly
demonstrated the temporal transtentorial hernia in 48 of 102 patients with
unilateral high intracranial pressure, but the orbitomeatal line scanning method
was not able to show this direct finding. The projected tissue of the temporal
lobe could be obviously shown and the degree of the hernia could be judged
directly on the CT imaging with the vertical-to-clivus scanning method.
Therefore, the CT diagnosis criterion of the hernia was suggested as follows: the
hernia would be determined if the downward shift of the temporal lobe was more
than 3 mm and suspected if less than 3 mm with ipsilateral high intracranial
pressure. CONCLUSION: This new method presented a superiority in showing the
temporal transtentorial hernia for the patients with a cranial emergency.
PMID- 9642310
TI - Effects of prostaglandin E2 and all-trans retinoic acid combination on induced
differentiation of human acute promyelocytic leukemia NB4 cells.
AB - OBJECTIVE: A human promyelocytic leukemia (APL) cell line NB4 was used to
demonstrate the synergistic effects between all-trans retinoic acid (ATRA) and
prostaglandin E2 (PGE2) on growth inhibition and cytodifferentiation induction.
METHODS: NB4 cells were cultured in the presence of either ATRA or PGE2 as a
single agent or in combinations at various ratio. Cell growth was measured and
myeloid differentiation was tested on consecutive days over the whole course of
culture. RESULTS: PGE2 and ATRA synergistically induced the myeloid
differentiation of NB4 cells. In comparison with ATRA alone, the combination of
PGE2 with ATRA caused an almost 20-fold decrease of effective concentration of
ATRA. CONCLUSION: The combination of ATRA and PGE2 at an appropriate ratio may
provide a convenient oral regimen of combined differentiation therapy for a
better clinical outcome in APL patients.
PMID- 9642311
TI - Clinical features of 201 cases with Duane's retraction syndrome.
AB - OBJECTIVE: To summarize the clinical features of 201 cases with Duane's
retraction syndrome (DRS) and discuss its differential diagnosis. METHODS: We
retrospectively summarized the 201 cases from 1979 to 1996. The clinical features
including chief complaints, sexual distribution, age at first visit, laterality,
type of presentation, ocular deviation in the primary position, refractive
errors, amblyopia, globe retraction, change of the palpebral fissure, upshoot and
downshoot in adduction, binocular single vision, and its associated ocular and
non-ocular anomalies were analysed. RESULTS: There were 99 males and 102 females
with a female-to-male ratio 1:1. The 65.88% of DRS cases had left eye involvement
with two-to-one predilection for the left eye. The most common form of the
syndrome was type I (184 patients, 91.54%). Exotropia was the most common
deviation in the primary gaze (72 patients, 35.8%). Among 118 patients, most had
abduction deficits, globe retraction in adduction, and faceturn as to maintaining
single binocular vision. Crocodial tears (26 patients, 11.93%) was the most
frequently encounted ocular abnormalities. CONCLUSIONS: Diagnosis of DRS in a
typical case is not difficult, however, children with bilateral abduction
deficits which may mimic DRS must be differentiated from the following four
motility disorders, namely, abducens nerve palsy, Moebius syndrome, congenital
oculomotor apraxia, and congenital or infantile esotropia.
PMID- 9642312
TI - A survey of antipsychotic treatment for schizophrenia in Hong Kong.
AB - OBJECTIVE: To obtain information on prescription pattern of antipsychotic drugs
for schizophrenic in-patients treated in public hospitals in Hong Kong. Four main
areas of antipsychotic treatment are reported in this paper: (1) doses of
antipsychotic drugs, (2) the practice of giving multiple antipsychotic agents
simultaneously, (3) use of antipsychotics in divided daily doses and (4) co
administration of antipsychotic and antiparkinson drugs. METHODS: A cross
sectional survey of prescriptions of antipsychotic medication for a
representative sample of 957 schizophrenic in-patients was conducted on a
randomly chosen census day. Questionnaire items included basic demographic and
clinical data, as well as inventory for all medications received by patients on
census day. RESULTS: The mean antipsychotic dose was 854 +/- 759 (median: 600;
range) 0-4450) mg CPZeq. Over two-third of the patients were given more than drug
concurrently while less than 20% received the medication in multiple divided
doses. Antiparkinson drugs were prescribed with antipsychotic medication in
69.61%, of the subjects. There were few differences between acute and chronic
patients with respect to their respective prescription patterns. CONCLUSIONS:
Antipsychotic treatment of schizophrenic inpatients in Hong Kong is largely in
accord with international standards. Problematic areas identified for closer
scrutiny include the concurrent use of more than one antipsychotic drug for both
acute and chronic patients, and the higher than recommended doses for
antipsychotic drugs and frequent use of antiparkinson medication for chronic
patients. Dissemination of these results, accompanied by continuing medical
education about psychopharmacology, are planned to further improve the quality of
treatment for schizophrenic patients.
PMID- 9642313
TI - Changes of ultrasonography and two serum biochemical indices for hepatic fibrosis
in schistosomiasis japonica patients one year after praziquantel treatment.
AB - OBJECTIVE: To observe the changes of abdominal sonography and 2 biochemical
indicators for hepatic fibrosis before and after treatment with praziquantel in
schistosomiasis japonica patients. METHODS: Fifty-five persons infected with
Schistosoma japonicum and treated with praziquantel were examined with
ultrasonography and serum hyaluronic acid (HA) and type III procollagen (PC III)
before and 1 year after treatment, and their data were compared with those in 55
normal controls. RESULTS: With comparison of the data before praziquantel
treatment, the length of the left liver lobe and the spleen in 55 patients all
decreased (P < 0.01) 1 year after treatment. No significant change was seen in
interior diameter (d) of the portal vein, while a decrease in the ratio of the
exterior diameter (D) and interior diameter of the second branch of the portal
vein was very significant (P < 0.01). Compared with the data in normal control,
significantly higher levels in the thickness of the left lobe, the maximum
oblique diameter of the right lobe, the length of the spleen, spleen index, the
interior diameter of the portal vein and D/d ratio were seen in the patients both
before and after treatment. The abnormal rate of the 2 serum parameters for
hepatic fibrosis decreased significantly after treatment. CONCLUSIONS: Parameters
of hepatic fibrosis either by ultrasonography or by the 2 biochemical tests
showed a significant improvement in 55 patients 1 year after treatment, although
some of the indices did not yet return to normal levels.
PMID- 9642314
TI - Observation of developing cercaria of Schistosoma japonicum on ultrastructural
level and remarks at its morphology of mature stage.
AB - OBJECTIVE: To study the developing cercaria of Schistosoma Japonicum (S.
japonicum) on ultrastructural level by transmission electron microscope (TEM) for
analyzing the morphological dynamic changes of the tegument, glands and
musculature. METHODS: Artificial infected Oncomelania hupensis were dissected
under dissecting microscope and the daughter sporocysts picked up for studying
the germinal cells stage (S1). The other embryonic cercaria were selected
according to the modified parameter of Chen and Bier (1972). The specimens were
prepared by conventional procedure of the laboratory of TEM and were observed by
Hitachi H600. RESULTS: Beside the germinal cell stage (S1), this is the first
chronological study on the morphological development of S. japonicum cercaria
from S2-S5 concerning the tegument and its elements (glycocalyx, sensory papilla,
basal lamina and spine), head and acetabular gland and musculature of the body
and tail. This article discusses the ultrastructural morphological differences
from prior authors and emphasizes on the postacetalar gland and the pattern of
tail musculature of the matured stage cercaria. CONCLUSIONS: According to the
cell division and differentiation, the process of development may be divided into
5 stages: S1, the single germinal cell stage; S2, the germinal ball stages: major
multiplication and minor differentiation; S3, tail budding embryonic stage, both
active in multiplying and differentiating; S4, the pre-matured stage, major
differentiation and minor multiplication; and S5, the fully matured stage
(completing the differentiation).
PMID- 9642315
TI - Studies on the transmission potential of filariasis in controlled areas of Henan
Province.
AB - OBJECTIVE: To study the regular pattern of growth and declination or the
transmission potential of filariasis after the disease was basically (the
microfilarial rate was lower than 1%) in Henan Province in 1987. METHODS:
According to the distribution of filaria species and original microfilarial rate,
in 7 surveillance sites in 7 counties (cities) the etiology and mosquito vector
surveys were carried out continuously during 1988-1995 and no control measurement
for pathogen was taken. RESULTS: Ten residual microfilaremias became negative
gradually in the first 6 years and no new microfilaremias occurred during 1988
1995. During 1993 to 1995, the microfilaremias rate of population in the sites
was 0. The natural infection rates of filarial larvae in vector mosquito were
0.1%-0. During the 8 years, 15 vector mosquitos were positive with a total of 18
filarial larvae which were all of first or second-stage larvae. The C. pipiens
pallens was the main vector, the second was A. sinensis, with a small number of
C. fatigans and A. anthropophagus. The man-biting rates of mosquitoes for outdoor
sleepers fluctuated greatly, the highest one was 360.6 mosquitoes/person per
night and the lowest, 7.2. The man-biting rates of mosquitoes for sleepers inside
mosquito-net was about 1 mosquito/person per night. The proportion of multiparous
mosquitoes also fluctuated more greatly, the highest one was 88.1% and the lowest
27. 2% According to the data described above, the man-biting rate of vector
mosquito which contained filarial L3 was 0. CONCLUSIONS: The results suggested
that after the microfilarial rate was lower than 1%, the residual microfilaremias
became negative gradually in 3-6 years, and the transmission of the disease was
blocked. Therefore, in the areas where filariasis was basically controlled,
elimination of the disease was attainable within sight.
PMID- 9642316
TI - Study on stress distribution of the condyle.
AB - OBJECTIVE: To investigate the internal state of stress distribution in healthy
human condyles and to offer some references for application of the
temporomandibular joint (TMJ) biomechanics. METHODS: Six male volunteers were
selected to perform CT examination of the TMJ with 1.5 mm-thick sections at 1.5
mm intervals. Three dimensional image reconstruction of the joint was performed
in the SUN workstation and the CT data were converted into the decimal system.
The three dimensional finite element model mesh generation resulted from 1188
elements and 264 nodes in each condyle. Stress calculation was performed with SAP
V program, and the results were converted into mechanical density scalar. During
the study, the internal state of stress distribution on each side condyle in
every subject was analysed on the basis of loading on the anterior articular
surface of the condyle. RESULTS: Stress was concentrated in the anterior
articular surface of the condyle and was highest at the loading point. The
condylar cortical bone was the main load-bearing area. The level of stress
distribution in the cancellous bone of the condyle was very low. Near condylar
neck stress was well-distributed on the cortical. The internal state of stress
was essentially symmetrical on the same cuts of both side condyles. CONCLUSIONS:
The results showed that three dimensional finite element analysis may indicate
the internal state of stress distribution in the condyle, suggesting that a
combination of the three dimensional finite element methods and the three
dimensional imaging technique may be a useful means for diagnosis and treatment
of TMJ diseases.
PMID- 9642317
TI - Eosinophilic granuloma of the cervical spine.
PMID- 9642318
TI - Retinal capillary pericyte apoptosis in early human diabetic retinopathy.
AB - OBJECTIVE: To investigate the nature of retinal capillary pericyte dropout in
early human diabetic retinopathy. METHODS: In the present study, neural retinas
of 12 postmortem eyes from 6 patients (3 diabetic and 3 nondiabetic) were first
fixed in buffered formaldehyde and then digested with trypsin. The preparations
of trypsin-digested retinal blood vessels were stained with terminal
deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique
and then with perdiodic acid-Schiff technique (PAS), and counter-stained with
hematoxylin to evaluate DNA fragmentation of cell nuclei and diabetic changes of
retinal capillaries. RESULTS: TUNEL-positive apoptotic pericytes were observed in
retinal capillaries in all three diabetic patients in this study. The TUNEL
positive pericytes were presented as darker stained cells with PAS-hematoxylin
staining. A few TUNEL-positive retinal capillary endothelial cells were
discovered in both eyes of one of the three diabetic patients. Neither TUNEL
positive pericytes nor positive endothelial cells were found in the three
nondiabetic patients. A variety of typical diabetic microvascular changes were
noticeable with PAS-hematoxylin staining in trypsin-digested retinal preparations
from diabetic patients. These changes included thickened capillary walls,
microaneurysms, "ghost-cell"-appearance of pericytes, acellular segments of
capillaries, and a decreased ratio of retinal capillary pericytes to endothelial
cells. All of these changes are characteristics of diabetic retinal
microangiopathy. CONCLUSIONS: Retinal capillary pericyte apoptosis is a specific
form of cell death which occurs during the early development of diabetic
retinopathy. The significant decrease in the ratio of pericytes to endothelial
cells and the predominant TUNEL-positive pericytes over endothelial cells suggest
that a greater impact of apoptosis-related mechanisms occurs in pericytes than in
endothelial cells and, thereby, a greater loss of pericytes takes place in early
diabetic retinopathy. Apoptosis, therefore, is an important mechanism of pericyte
dropout in the early diabetic retinopathy.
PMID- 9642319
TI - Color Doppler imaging diagnosis of intra-ocular tumor.
AB - OBJECTIVE: To demonstrate the color Doppler imaging (CDI) of intra-ocular tumors
and its importance in the diagnosis of these tumors. METHODS: Ninety-two patients
with intra-ocular tumors (105 eyes) were examined by using CDI to observe the
vasculature of these tumors, and using SAS soft ware to analyze the results.
RESULTS: Blood flow signal was found in retinoblastoma, melanoma of choroid,
angioma of choroid, angioma of optic disc, Coats' disease, persistent
hyperplastic primary vitreous (PHPV) and metastatic tumors of choroid, but not
found in choroid osteoma and melanocytoma of optic disc. The blood flow decreases
in central retinal artery in choroidal melanoma and also in ophthalmic artery,
central retinal artery and posterior ciliary artery in angioma of choroid (P <
0.01). It was found that blood velocity is much faster in choroidal melanoma than
in choroidal angioma (P < 0.05). CONCLUSIONS: CDI is very important and helpful
in the diagnosis of intra-ocular tumors.
PMID- 9642320
TI - Correlation between retinal fluorescein angiography and blood viscosity and other
factors in patients with primary open angle glaucoma.
AB - OBJECTIVE: To investigate the correlation among retinal fluorescein angiography,
blood viscosity, and other factors in patients with open angle glaucoma (POAG).
METHODS: Multiple step regression analysis was made to investigate the
correlation between each of the following blood vessel filling times: the arm
choroid (A-CT), arm-retinal artery (A-AT), and retinal artery-venous (A-VT) of
the fundus fluorescein angiography (FFA) in 122 eyes with POAG and each of the
following related factors in hemorrheology: whole blood apparent viscosity at
low, medium and high shear rates, plasma viscosity and hematocrit. Also, the same
analysis was applied to investigate the correlation between each of the A-AT, A
VT of the FFA in 70 eyes with POAG and the following factors: systolic blood
pressure, diastolic blood pressure, age and whole blood apparent viscosity at low
shear rate. RESULTS: The whole blood apparent viscosity at low shear rate was
closely related to A-CT and A-AT, while hematocrit was closely related to A-VT of
the FFA. The whole blood apparent viscosity at low shear rate and age, especially
the whole blood apparent viscosity, was closely related to A-AT, A-VT of the FFA.
CONCLUSION: Blood viscosity can affect the filling times of the FFA in POAG.
PMID- 9642321
TI - A corneal topographic analysis of astigmatism after excimer laser photorefractive
keratectomy.
AB - OBJECTIVE: To identify the astigmatism changes after excimer laser
photorefractive keratectomy (PRK) and the visual influence of astigmatism.
METHODS: 109 myopic eyes followed up for more than 1 year were analyzed by
videokeratography, and their visual acuities were examined. Before the operation,
the astigmatic errors with cycloplegic refractive examination were -1.00
approximately -2.00 D. RESULTS: The position of astigmatism axis was basically
consistent with that in corneal topography, but in astigmatism diopter there were
some differences between the cycloplegic examination and topographic analysis. A
stigmatism was found in 62% of the eyes, asymmetrical in 33% and against-the-rule
in 5% by using topographic analysis. There was little change observed in the
position of astigmatism axis after PRK observed. Some changes of postoperative
astigmatism diopter were seen in different periods. It increased in the
postoperative 10 days or 1 month, and afterwards gradually decreased and became
stable in 6 months to 1 year. The postoperative residual astigmatism was low in
degree, and did not affect the visual acuity. The actually corrected diopter was
within the anticipated corrected diopter range of +/- 1.00 D. accounting for
97.4%. CONCLUSION: By using spherical equivalent method of calculation in PRK,
the refractive correction of the operation cases with myopia and low degree of
astigmatism (< -2.00 D) was satisfactory.
PMID- 9642322
TI - Stent thrombosis with different types of intracoronary stents: is it still a
problem?
AB - OBJECTIVE: The reported results of intracoronary stenting with Palmaz-Schatz
stents using the low dose anticoagulation protocol have been encouraging and no
stent thrombosis was observed. The effectiveness of such method extending to the
use of other types of stents was therefore evaluated in this study. METHODS: All
patients followed the anticoagulation protocol (heparin and warfarin) using non
heparin-coated stents. From September 1995, 92 patients received intracoronary
stenting (69 men, 23 women, mean age 60.9 years). Altogether 117 stents were
implanted in 99 target arteries and 106 lesions. RESULTS: A total of 50.4% of the
stents were bare stents (stents without protective sheaths). Both coil stents and
slotted tubular stents were used. Stenting was performed without the guidance of
intravascular ultrasonography and high-pressure poststenting inflation was used
in only 24.0% of patients with less than optimal angiographic results. The mean
(+/- SD) coronary minimum luminal diameter changed from 0.63 +/- 0.39 mm to 3.12
+/- 0.48 mm immediately after stenting. Both stent thrombosis rate and femoral
bleeding complication rate remained at 0%. Four bare stents could not be deployed
in the first instance but without sequels. No morbidity nor mortality was
recorded. The mean hospital stay remained at a mean of 4.5 days. All patients
(100%) were followed up regularly. The mean (+/- SD) clinical follow-up period
was 229 +/- 173 days. Clinical symptoms improved in all patients. CONCLUSIONS:
These findings further support that the method is safe and stent thrombosis was
not observed. Post-stenting recoil was more with coil stents. Dislodgment and
potential risk of embolization could not be underestimated with bare stents. The
restenosis rate between different types of stents remains to be determined.
PMID- 9642323
TI - Some changes of receptor and postreceptor signal transduction regulated by
somatostatin in pituitary hGH-secreting adenomas.
AB - OBJECTIVE: To investigate the disturbance in the function of SRIF receptor, Gi
protein and Ca2+ channel in hGH adenoma cells and to evaluate their significance
in the pathogenesis of pituitary hGH adenomas. METHODS: All 25 patients with
pituitary hGH adenoma who were involved in this study had typical acromegalic
manifestation and high fasting serum hGH levels of > 5.0 micrograms/L which were
not suppressed to < 3.0 micrograms/L by oral glucose tolerance test. The
pituitary hGH adenoma tissue obtained from transphenoidal operation was digested
by collagenase and the dispersed adenoma cells were cultured in the monolayer.
The effects of octreotide (SMS), a long-acting agonist of somatostatin, on hGH
secretion and intracellular cAMP level were observed and the influences of
pertussis toxin (PT), an inhibitor of Gi protein, and Ca2+ ionophore A23187 or
KCl on the inhibitory action of octreotide on hGH secretion were also
investigated in the cultured pituitary hGH adenoma cells. RESULTS: A total of
16.0% (4/25) of cultured pituitary hGH adenomas did not respond to octreotide
(100 nmol). The inhibitory effect of octreotide on hGH secretion was not blocked
by PT (50 ng/ml) and A23187 (10 mumol) or KCl (22.5 nmol) in 31.6% (6/19) and 35%
(7/20) of hGH adenomas, respectively. The effects of octreotide on hGH secretion
and intracellular cAMP levels were studied in 10 cultured hGH adenomas.
Octreotide suppressed both hGH secretion and cAMP levels in 5 cases; inhibited
only hGH secretion or the cAMP level in 3 cases and 1 case respectively; and
affected neither hGH secretion nor cAMP level in the last case. CONCLUSION: There
were abnormalities in the SRIF receptor and/or postreceptor signal transduction
in 16.0% of hGH adenomas which did not respond to octreotide. The defects in Gi
and/or Ca2+ channels were found in 52.4% (11/21) of hGH adenomas which had
responded to octreotide. These defects might induce diminution of the inhibitory
action of SRIF on hGH secretion and might be the causes of hypersecretion in some
pituitary hGH adenomas.
PMID- 9642324
TI - Analysis of tumor specific immunoglobulin gene rearrangement in peripheral blood
B-cells of multiple myeloma patients by a PCR-SSCP method.
AB - OBJECTIVE: To analyze the clonal relationship between lymphocytes in peripheral
blood (PB) and myeloma cell in bone marrow (BM) for proving the existence of
circulating tumor cells in multiple myeloma (MM) patients. METHODS: Eighteen
patients with MM who have no cytomorphologic plasma cells and CyIg+ cells in PB
demonstrated by anti-kappa and anti delta MoAbs using ABC method were involved in
the present study, including 3 cases in phases I-II and 15 cases in phase III.
The complementary determining region 3 (CDR3) of immunoglobulin heavy chain (IgH)
gene was amplified by polymerase chain reaction (PCR). We further analysed the
single strand conformation of the PCR products by single strand conformation
polymorphism (SSCP) analysis to detect the mononuclear cells in PB and BM of the
patients simultaneously. RESULTS: The same PCR products of IgH-CDR3 gene with BM
samples were found in PB of 11 MM patients. The same PCR products and single
strand conformation in both PB and BM were found in 9 cases. CONCLUSIONS: This
study has proved the presence of identical clonal malignant cells in PB and BM of
MM patients. B cells are involved in the pathogenesis of MM.
PMID- 9642325
TI - Effects of cyclosporine A on serum and urinary soluble interleukin-2 receptor in
patients with lupus nephritis.
AB - OBJECTIVE: To evaluate the association of the level of urine and serum soluble
interleukin-2 receptor (sIL-2R) with disease activity and response to
cyclosporine A (CsA) therapy in patients with lupus nephritis (LN). METHODS:
Sixteen hospitalized patients with LN were studied. At admission, fifteen
patients had type IV-LN and one had type V-LN. All patients received CsA 6 mg/kg
per day for 6-8 weeks, then tapered off gradually to 2 mg/kg per day. The levels
of urinary and serum sIL-2R were determined by enzyme-linked immunosorbent assay
(ELISA). Serum antinuclear antibody (ANA), anti-dsDNA antibody (A-ds-DNA),
complement C3 and C4, total IgG, creatinine, urinary red blood cells and protein
excretion, and lymphocyte subpopulations in the peripheral blood were also
measured before and after CsA treatment. RESULTS: In LN patients, both urinary
(534 +/- 101 U/ml) and serum SIL-2R levels (326 +/- 148 U/ml) were higher than
those in normal controls. These findings were associated with higher levels of
peripheral blood CD4 + and CD8 + lymphocytes (29.3 +/- 4.24 and 28.6 +/- 9.12%),
higher titer of serum anti-ds-DNA, lower levels of serum complement C2 and C4
(0.98 +/- 0.23 and 0.24 +/- 0.12 g/L), as well as more proteinuria (Upro 2.99 +/-
0.76 g/24 hrs) and hematuria (URBC 83.9 +/- 95.2 10(4)/ml). These abnormalities
were gradually ameliorated by CSA therapy. The changes in the levels of both
serum (116 +/- 58.6 U/ml) and urine (136 +/- 43.2 U/ml) SIL-2R induced by CsA (at
8 weeks) were correlated with the changes in the levels of CD4 + and CD8 + cells
(23.2 +/- 3.30 and 26.7 +/- 3.54%), degrees of immune abnormalities (serum C3 and
C4 1.28 +/- 0.14 and 0.42 +/- 0.06 g/L), and renal injuries (Upro 1.07 +/- 0.46
g/24 hrs, URBC 5.82 +/- 3.15 10(4)/ml). CONCLUSIONS: These results suggest that
serum and urinary sIL-2R are sensitive markers for the disease activity in
patients with LN. CsA, a powerful immunosuppressive agent, significantly improves
both immunologic disorders and renal functional impairments, the mechanism of
which on patients with LN appears to inhibit the lymphocyte activation in the
peripheral blood and renal tissues as indicated by the decrease in sIL-2R levels.
PMID- 9642326
TI - Guillain-Barre syndrome: clinical analysis and pathological study on sural nerve
biopsy of forty cases.
AB - OBJECTIVE: To make clinical analysis and pathological study on 40-case Gullain
Barre syndrome with sural nerve biopsy. METHODS: A total of 90 cases of GBS were
retrospectively analyzed of which sural nerve biopsies were performed in 40
cases. The type of GBS was determined according to Asbury and Ropper criteria,
and its correlation with pathological findings was studied. RESULTS: In the 40
biopsy cases, demyelination was the predominant pathological change in 38 cases.
Mild axonal degeneration was also seen in 13 of the 38 cases. Prominent axonal
degeneration was seen in only 2 of 13 cases. The increased monocyte infiltration
and varied capillary permeability were observed in 19 of 25 cases. Onion-bulb
like changes were seen in 6 cases. CONCLUSION: We studied the correlation between
paresthesia and the pathological findings of sural nerve biopsy and concluded
that sural nerve biopsy is very useful in the diagnosis of GBS and its variant.
PMID- 9642327
TI - Clinical curative effects of dimercaptosuccinic acid on hepatolenticular
degeneration and the impact of DMSA on biliary trace elements.
AB - OBJECTIVE: To observe the biliary copper content of nonhepatolenticular
degeneration (HLD) controls and changes in the trace elements in the bile,
cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients
before and after dimercaptosuccinic acid (DMSA) treatment in order to further
explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA
on HLD patients. METHODS: A consecutive series of 20 patients with HLD were given
DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day.
Their bile, cerebrospinal fluid, blood and urine samples were obtained before and
after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary
samples of 22 non-HLD controls were taken by drainage tube after surgical
operation. Hitachi-208 atom absorption spectrophotometer was used to assay the
content of copper, zinc and iron of each sample. RESULTS: DMSA could effectively
improve the symptoms such as dysphasia, salivation, dysphagia and darkening of
the skin; limb trembling and myotonia came second; but it showed no obvious
effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It
was effective for the patients who were younger and had no obvious hepatic
damage. No serious side effects were seen through the course of treatment.
Laboratory study showed that biliary copper content of HLD patients was evidently
lower than that of non-HLD controls (P < 0.01); DMSA could evidently improve
biliary copper excretion besides clearly increase urinary copper excretion (P <
0.01) and had nothing to do with biliary zinc excretion (P > 0.05). CONCLUSIONS:
Biliary copper excretion disturbance participates directly in the pathophysiology
of copper retention of HLD patients. DMSA is a favorable cupruretic drug for
patients with HLD.
PMID- 9642328
TI - Anti-acetylcholinesterase antibody in myasthenic syndrome.
AB - OBJECTIVE: To examine the relationship between antibodies to acetylcholinesterase
and myasthenic syndrome. METHODS: Serum class specific antibodies to
acetylcholinesterase and acetylcholine receptor were prepared with solid phase
enzyme-linked immunosorbent assay in 51 patients with myasthenic syndrome, 31
controls with other neurological diseases (diseased controls) and 44 normal
controls. RESULTS: The positive rate of anti-acetylcholinesterase antibody in
patients with myasthenic syndrome was 25%, while the results of the other two
control groups were negative. Furthermore, the positive rate in patients without
myasthenia gravis was 45%, which was much higher than that (13%) in those with
myasthenic gravis. CONCLUSION: Anti-acetylcholinesterase antibody may play a role
in the pathogenesis of myasthenic syndrome.
PMID- 9642329
TI - Diagnosis of intrathoracic masses by transesophageal color Doppler
echocardiography.
AB - OBJECTIVE: To evaluate the value of transesophageal color Doppler
echocardiography in the diagnosis of intrathoracic masses. METHODS: Twenty
patients with intrathoracic masses were examined by transesophageal
echocardiography (TEE), including 12 patients with central lung masses and 8 with
mediastinal masses. The neoplasms were explored by two-dimensional realtime
ultrasonography, Doppler color flow imaging (DCFI) and pulsed Doppler (PD). The
results were compared with computed tomography (CT), operative and pathological
examination findings. RESULTS: We were able to identify the size, structure
(solid or cystic), anatomic relationship, metastatic lymph nodes and venous
carcinoembolus of the masses. Furthermore, the hemodynamic data in the
vasculature inside the masses were detected. CONCLUSIONS: As a new method, TEE
with Doppler technique is not only valuable in differentiating malignant and
benign neoplasms but also useful for preoperative evaluation of the mass
resectability in patients with intrathoracic neoplasms.
PMID- 9642330
TI - Complications of laparoscopic cholecystectomy in China: an analysis of 39,238
cases.
AB - OBJECTIVE: To investigate the complications of laparoscopic cholecystectomy in
China. METHODS: All Chinese articles about laparoscopic cholecystectomy published
between April 1994 and November 1995 were identified through CMCC (Chinese
Medical Computerized Contents). From more than 600 titles, 105 articles were
screened for analysis. Another 21 articles from the 6th Biliary Surgical Congress
and 300 cases from the General Hospital of PLA were added. A total of 39,238
cases of laparoscopic cholecystectomy from 91 hospitals were studied. RESULTS:
Severe complications of laparoscopic cholecystectomy were identified in 409
(1.04%) patients, including bile duct injury (in 0.32% of patients),
postoperative cystic duct leak (0.11%), postoperative bile leak (0.20%),
peritoneal abscess (0.07%), bowel injury (0.06%) and postoperative hemorrhage
(0.1%). Fourteen postoperative deaths (0.04%) resulted from operative injury.
CONCLUSIONS: The data demonstrate that laparoscopic cholecystectomy is an
operation associated with low morbidity and mortality rate, but bile duct injury
is still a major problem. Complications of laparoscopic cholecystectomy can be
minimized by improving operative procedure.
PMID- 9642331
TI - Clinical study of desflurane on low flow anesthesia compared with sevoflurane and
enflurane.
AB - OBJECTIVE: To compare the hemodynamic change, course of recovery and adverse
reaction in desflurane, sevoflurane and enflurane inhalation under low flow for
patients undergoing selective abdominal surgery. METHODS: Following thiopental
induction, 42 patients were divided into three groups: the first group received
desflurane, the second sevoflurane and the third enflurane. During surgery, one
of the agents around 1 minimum alveolar concentration (MAC) was used for
maintenance, with fresh gas flow of 0.3-0.5 L/min for either desflurane or
enflurane, and (0.8-1.0) L/min for sevoflurane. Heart rate (HR), blood pressure
and end-tidal anesthetic concentration were monitored continuously. Time
intervals from cutting off anesthetic to patient opening eyes, following
commands, stating the time and location and recalling date of birth were all
recorded. In addition, postoperative nausea or vomiting was traced. RESULTS:
Desflurane caused the least cardiovascular depression. with mean arterial
pressure (MAP) maintained significantly better at 10, 30 and 60 minutes of
surgery and with HR stabilized right after incision as well. Its emergence was 2
times faster than sevoflurane, and 5-6 times quicker than enflurane. However,
nausea or vomiting was found the lowest in patients receiving sevoflurane, though
no distinct difference was shown between desflurane and enflurane. Nevertheless,
patients under desflurane suffered less. CONCLUSIONS: Desflurane offers
significant advantages for clinical anesthesia maintenance over sevoflurane and
enflurane. It provides minimal cardiovascular depression, much quicker recovery,
yet still causes some nausea during emergence.
PMID- 9642332
TI - Preliminary observation on the metabolism in spontaneous hereditary diabetic
Chinese hamster (Shanyi colony).
AB - OBJECTIVE: To observe the changes of tissue lithium content and its relationship
with glucose metabolism in spontaneous hereditary diabetic Chinese hamsters
(SHDCH). METHODS: Twenty diabetic and ten normal Chinese hamsters were paired and
separated randomly into four groups: controls (C), diabetics (D), controls
treated with lithium carbonate (CT) and diabetics treated with lithium carbonate
(DT). The lithium carbonate treatment was administrated with drinking water
containing lithium carbonate (0.2 mg/ml). Blood glucose levels were determined at
0, 1, 3, 5, 6th month, and insulin levels at 1, 3, 6th month. The lithium
contents in liver, kidney and muscles were determined at the end of 6th month,
using wet digestion assay and ICP-AES. Concentrations of fructosamine, lactic
acid, GPT, BUN were also evaluated. RESULTS: The data showed that in Group D the
lithium levels in hepatic tissue were lower than in Group C (P < 0.05), and
lithium contents in kidney and muscle also decreased. In Group DT, the lithium
contents in tissues were higher than in Group D (P < 0.05) and similar to Group
C. Blood glucose levels and fructosamine concentrations decreased while insulin
and lactic acid levels did not alter significantly. GPT and BUN levels did not
change in both Group CT and Group DT. CONCLUSIONS: There is lithium deficiency in
hepatic, renal and muscular tissues from diabetic Chinese hamsters. Low-dose and
six-month-treatments of lithium carbonate can improve tissue lithium deficiency
and glucose metabolism, and do not damage liver and kidney functions.
PMID- 9642333
TI - Effects of peroxovanadate complexes on reducing glycemia in diabetic rats and
translocation of glucose transporter.
AB - OBJECTIVE: To demonstrate the hypoglycemic effects and translocation of glucose
transporter (Glut 1 and Glut 4) promoted by peroxovanadate and nicotinic acid
complexes (nicotinic chelated bitriperoxovanadate, POR; N-O nicotinic chelated
peroxovanadate, POV) in streptozotozin-induced diabetic rats. METHODS:
Peroxovanadate complexes of nicotinic acid (POR and POV) were prepared and
characterized in laboratory. POR, POV and vanadate were administrated in drink
water. The muscles from diabetic rats were subjected to prepare plasma membrane
and microsome membrane. Antibodies to COOH-terminal of glucose transporter were
used in Western Blot to evaluate the translocation. RESULTS: POR and POV showed
markedly hypoglycemic effects in streptozotocin (STZ)-induced diabetic rats. POV,
which may be a N-oxide compound of peroxovanadate, have high potency of acute
effects comparing to carboxylate-complexes of peroxovanadate (POR). In chronic
tests, 1 mg/kg oral pathway POR could significantly reduce the plasma glucose
levels over four week's treatment, whereas the same dose of single sodium
vanadate or nicotinic acid did not have hypoglycemic effects. The net vanadium
intake is about 1/90 of single effectively vanadate treatment. The Western Blot
showed that POR increased the translocation of Glut 4 and Glut 1 from
intracellular site of membrane. CONCLUSIONS: Peroxovanadate-nicotinic acid
complexes (POR and POV) are the novel vanadyl that acutely and markedly reduce
plasma glucose in a lower dose comparing to vanadate in STZ-DM rats by oral
administration. Translocation of glucose transportor may take a part in their
hypoglycemic effects.
PMID- 9642334
TI - Collecting duct carcinoma of the kidney.
AB - OBJECTIVE: To describe the clinical, pathologic and immunohistochemical
characteristics of collecting duct carcinoma (CDC) of the kidney. METHODS: Five
cases of CDC (3 males and 2 females, aged 41 to 67 years) were identified between
January, 1990 and December, 1994. Routine histopathologic study and
immunohistochemical examinations of the surgical specimens were performed.
RESULTS: Four patients underwent radical nephrectomy; 3 have been alive without
evidence of recurrence for 3 months, 2 years and 2.5 years, respectively after
the operation. Bone metastasis was noted 2 months after the operation in 1 case.
One patient was submitted to simple nephrectomy because of extensive regional
node involvement and died of lung metastasis 14 months after the surgery.
Grossly, the tumors were usually grey-whitish in color and located in the renal
medulla. Microscopically, the characteristic structure of tubulo-papillary
pattern could be identified. Marked desmoplastic reaction was noted and atypical
hyperplastic changes were found in the adjacent collecting ducts.
Immunohistochemical studies revealed positive results to epithelial membrane
antigen, high molecular weight cytokeratin and peanut agglutinin. CONCLUSION: CDC
of the kidney is a rare disease with a poor prognosis. Radical nephrectomy is
recommended even if the tumor is small.
PMID- 9642335
TI - Preliminary study of the effects of metoprolol and propafenone on ventricular
arrhythmia with positive ventricular late potential.
AB - OBJECTIVE: To compare the effects of metoprolol and propafenone in patients with
ventricular arrhythmia (VA) of positive ventricular late potential (VLP) and to
discuss the effect of medicine on high risk VA. METHODS: 30 A total of 128
patients (78 males and 50 females) with VA of positive VLP were randomly divided
into 3 groups. Groups A and B were given metoprolol and propafenone respectively,
group C was given vitamin C as placebo. Twenty-four hours dynamic
electrocardiogram and VLP were examined before treatment and 4 weeks after
treatment. RESULTS: Propafenone could effectively control VA but could not
reverse positive VLP to negative meanwhile it had proarrhythmia effect (2/40),
metoprolol could effectively control VA (38/46) and reverse positive VLP to
negative (39/46) with no obvious side effects. The dosage from 50 to 100 mg/day
made no difference. VA and VLP had no significant changes in group C.
CONCLUSIONS: Metoprolol is superior to other medicine for VA of positive VLP when
the patients have no contraindication of preceptor blocking agents.
PMID- 9642336
TI - Koshevnikov syndrome in a patient with MELAS plus syndrome: electron microscopic
and neuroimage studies.
PMID- 9642337
TI - Primary nasal ectopic pituitary adenoma: a case report.
PMID- 9642338
TI - Aspergillosis of the larynx: a report of 8 cases.
PMID- 9642339
TI - [Salvage surgery for cervical metastasis from nasopharyngeal carcinoma after
radiotherapy].
AB - One hundred and forty patients who had residual or recurrent lymph node
metastasis from nasopharyngeal carcinoma after radiotherapy underwent salvage
surgery. The overall 3 and 5 year survival rates were 50.1% and 27.3%, the 3 and
5 year local control rates were 48.3% and 27.3%, the 3 and 5 years distant
metastasis-free rates were 44.5% and 25.6% respectively. The most significant
factors influencing survival and local control rates were the size and the
involvement of the capsule of the lymph nodes. The size of the lymph node was the
only influencing fastor for distant-metastasis-free survival. Distant metastasis
was the most frequent factor of treatment failure (48.9%) followed by recurrence
of neck mass (14.4%). The authors considered that the salvage surgery is an
effective method in improving the survival rate. The reradiotherapy after surgery
or/ and adjuvant chemotherapy is a new area for further investigation.
PMID- 9642340
TI - [Study on expression of nm23-H1 gene in laryngeal cancer tissues].
AB - The nm23 gene is a metastasis suppressor gene. There are now two known isotypes
of human nm23, namely nm23-H1 and nm23-H2. Several investigators have reported
that reduced expression of nm23-H1 is associated with metastasis or disease
progression in some of the tumor cases. In this study, the expression of nm23-H1
mRNA in the human laryngeal squamous cell carcinoma was investigated by Northern
blot analysis. The levels of nm23-H1 mRNA were higher in cancers (n = 31) than in
the adjacent normal tissues (n = 7), but the difference was not significant (P >
0.05). There was a significant decrease of nm23-H1 mRNA levels in tumors with
lymph node metastasis (n = 11) as compared with those without (n = 20) (P <
0.01). Cancer tissues in clinical stages III-IV. (n = 23) also exhibited lower
levels of nm23-H1 mRNA expression than those in stages I-II (n = 8) (P < 0.05).
These results suggest that the nm23-H1 gene may play a role in the suppression of
lymph node metastasis or disease progression in laryngeal cancer.
PMID- 9642342
TI - [Speech restoration via a tracheo-esophageal tegmental valve fistula following
total laryngectomy].
AB - In order to restore the patients' speech function after total laryngectomy, the
speech restoration operation has been done successfully in 12 patients with
laryngocarcinomas by making tegmental valve fistula from esophageal flap and
tracheal tissue after total laryngectomy. First, the trachea and the esophagus
were separated, and a tissue flap 20mm in length from posttracheal wall was made.
Its upper end was 10mm in width, lower end 8 mm, laterally 5 mm x 6 mm, the
tracheal mucosa and cartilage were sewn up to from a tegmental valve, then, a
tissue flap 20 mm in length from the preesophageal wall was done with its upper
end 15 mm in width, lower end 10 mm. Then a tegmental valve fistula (speech-tube)
was made by sewing up two flaps crisscross and a 12F catheter was inserted into
the tegmental valve fistula as a supporter for 10 days. Finally, a tracheostomy
was performed by sewing up the trachea to the neck skin. All patients could speak
fluently and clearly after surgery and kept their sex and dialect characteristics
whereas without misswallowing. The operation is a perfect way for total
laryngectomy with speech restoration in patients with upper glottal or glottal
laryngocarcinomas.
PMID- 9642341
TI - [Prognosis of laryngeal carcinoma in youth].
AB - The prognosis of 55 cases of laryngeal carcinoma in young people had been
studied. The major factors mainly related to prognosis were smoking and
misdiagnosis, while the tumour differentiation might be not so important. There
was a high recurrence rate of 25.5% in the young patients and low 3- and 5-year
survival rates of 47.4% and 34.5% respectively. The mortality of 1-year after
surgery was 21.8%. The 3-and 5-year survival rates between total and partial
laryngectomy made no difference. The survival rate of patients with positive node
was lower. Early diagnosis is most important for young patients. Partial
laryngectomy and neck dissection must be performed as far as possible.
PMID- 9642343
TI - [Clinicopathological study on patterns of cervical lymph node metastases from
squamous cell carcinomas (SCC) of the head and neck].
AB - In order to investigate the patterns of cervical lymph node metastases from head
and neck SCC, serial sections were performed on 384 radical neck dissection (RND)
specimens. Positive lymph node was found in 60.4% RNDs. The cervical lymph node
spread from SCC in the head and neck regions including oral cavity, oropharynx,
hypopharynx and larynx has some predictable patterns, i.e., for primary SCC of
the oral cavity, the majority of cervical lymph node metastases were clustered at
levels I, II and III; and for primary carcinoma of the oropharynx, hypopharynx
and larynx, a majority of node metastases were located at levels II, III and IV.
The positive lymph nodes mainly distributed at only one level or consecutive
levels. The rates of pathologically positive lymph node and extranodal spread
grew with the increase of the clinical N-staging. It is suggested that
supraomohyoid neck dissection (levels I, II and III) is particularly applicable
to carcinomas of the oral cavity, and lateral neck dissction (levels II, III and
IV) is applicable to carcinomas of the oropharynx, hypopharynx and larynx in
patients with limited (N0 and N1) neck nodules, but for patients with N2 and N3
nodules, RND is neccessary to eradicate the nodal metastases. Moreover, the
postoperative radiotherapy is indispensable for ruling out the occult cervical
lymph node metastaese in selective neck dissection.
PMID- 9642344
TI - [Chemosensitivity test for head and neck cancers].
AB - The chemosensitivities of 27 fresh specimens of head and neck cancers were tested
with MTT assay to study the practicability and accuracy of the assay for the
examination of chemosensitivity in head and neck cancer patients. The
chemosensitivities among cancers of different primary sites, pathologic types,
histological differentiations, DNA ploidies and estrogen receptors were compared
in an attempt to evaluate the choice of anticancer drugs for individual
chemotherapy. Eight anticancer drugs: Methotroxate (MTX), Mitomycin C (MMC),
fluorouracil (5-Fu), Carboplatin (CBDCA), Pingyangmycin (PYM), Homoharringtonine
(HHA), Etoposid (VP16) and Vincristine (VCR) were included. The success rate of
MTT assay in the present study was 92.6% and the accuracy was relatively high.
The sensitivity sequence was PYM > HHA > MTX > CBDCA > MMC > 5-Fu > VCR > VP16,
which suggested HHA should be recommended first to the chemotherapy of head and
neck cancer. No chemosensitivity differences were found among different primary
sites histological differentiations and estrogen receptors. The chemosensitivity
of squamous cell carcinoma was significantly higher than that of adenoid cystic
carcinoma. The chemosensitivity of aneuploid tumor was significantly higher than
that of diploid.
PMID- 9642345
TI - [Impulsive angular acceleration evoked middle and long latency potentials in
guinea pigs].
AB - Middle and long latency evoked potentials have been successfully recorded in
guinea pigs with impulsive angular acceleration delivered by a specially
developed motor. The middle latency responses elicited by impulsive angular
acceleration had peaks at about 9 ms, 15 ms and 24 ms with a mean peak to peak
amplitude of about 28muV and the long latency responses after the delivering of
impulsive angular acceleration in guinea pigs composed of a triphasic wave with a
mean peak to peak amplitude of about 50 muV occurring during 32 ms to 130 ms with
respect to the start of head stimuli. A series of experiments lead to the
conclusion that the middle latency responses to impulsive angular acceleration
are middle latency vestibular evoked potentials. The long latency response
elicited by impulsive angular acceleration is not a specific response of auditory
or vestibular pathway.
PMID- 9642346
TI - [Studies on the fine structures of inner ear vessels in guinea pigs].
AB - In order to investigate the characters of inner ear vessels using the
microvascular corrosion casting technique and scanning electron microscope the
three-dimensional spatial picture of the vessels in cochlear basilar membrane,
utriculus, sacculus and three ampullae of guinea pig were observed. It was found
that arteriole coils were present in the modiolus ampullae, utriculus and
sacculus. The length of arterioles was therefore prolonged and could keep the
blood supply in inner ear stable. The possibility of blood coagulation in these
segments increased because the blood flow became slower here. Another character
was that the capillary networks appeared denser in stria vascularis and central
part of the crista, whereas the vessel meshes in basilar membrane of cochlea and
in planum semiculatum of ampullae were looser. These findings suggested that the
metabolism in stria vascularis and central part of the crista would be more
prosperous than that in the basilar membrane and planum semiculatum of ampullae.
PMID- 9642347
TI - [Application of laser scanning confocal microscopy in inner ear morphological
studies].
AB - Laser scanning confocal microscope (LSCM) enables one to observe both the surface
structure and the inner configuration in the same specimen, by its possibility of
direct, non-invasive serial optical sectioning of whole mounted specimens. The
potential value of LSCM in the field of inner ear morphological study was
evaluated. The configuration of upper parts of organ of Corti was observed with
the LSCM combined with double-stained fluorescence immunohistochemistry
technique. The actin filament of hair cells by phalloidin, and the cytokeratin of
supporting cells by monoclonal pan-anticytokeratin antibody. The stereocilia,
cuticular plate, and the cuticle-free area of hair cells were well demonstrated.
In the same specimen, the head plate of outer pillar cell, the phalangeal apical
plate and the phalangeal process of Deiter cells were clearly showed as well.
LSCM provide a new tool to the morphological study of organ of Corti.
PMID- 9642348
TI - [Immunohistochemical study on three peptidergic terminals in nasal mucosa in a
rat AR model].
AB - To study the density alterations of three peptidergic terminals in nasal mucosa
of allergic rhinitis (AR), an exhaustive immunohistochemical sutdy on the changes
of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in nasal mucosa
was carried out in a toluene-2, 4-isocyanate (TDI)-induced rat AR model. The
densities of all three tachykininergic terminals in nasal mucosa were
significantly increased (P < 0.01) in experimental group as compared with control
group. Increased staining, thickening of peptidergic terminals as well as
enlargement of varicosities were observed. The increased densities of three
tachykininergic terminals (SP, NKA and NKB) in nasal mucosa in rat AR model
indicates that tachykinins play an important role in the pathogenesis of AR.
PMID- 9642349
TI - [Furosemide test for diagnosis of endolymphatic hydrops: a clinical exploration].
AB - Furosemide test (FT) is a clinical method for the diagnosis of endolymphatic
hydrops (EH). Immediately preceding i.v. injection of 20 mg furosemide, a caloric
test was performed with 50 micromilligrams of water at 30 degrees C.
Nystagmography was employed to measure the maximum slow velocity of caloric
nystagmus. The test was repeated one hour after the injection. The two sets of
data were then compared. An increase beyond 22.97% was defined as positive. The
first group was composed of 54 patients of EH as the experimental group, and the
second group 54 patients with vertigo of non-EH as control. The positive rates of
the two groups were 70.4% and 25.9% respectively. It showed that FT was useful
for detecting EH. The percentage of directional preponderance (DP) was obviously
descended in the two groups after i.v. furosemide. Descending rate was 77.8%
(21/27) in the first group, which had reached the normal value in 9 cases. It was
showed that DP was important also for criticizing FT. The hearing of all subjects
was not damaged. When the renal function of the subject was normal and not
combined with the use of aminoglycoside antibiotics, the dose of FT was not
dangerous to the hearing and had few side reactions. The mechanism of dehydration
in hydropic labyrinth was presumed to be acute systemic diuresis, but the effect
in inner ear was unknown.
PMID- 9642350
TI - [Otoacoustic emissions and tinnitus].
AB - Methods of objective tinnitus testing exploration causes of tinnitus and the
relationship between OAE and tinnitus are reported. In 306 ears with tinnitus
(with or without hearing loss), Distortion Products Otoacoustic Emission (DPOAE),
Spontaneous OAE (SOAE) and Transiently Evoked OAE (TEOAE) were tested by ILO92
Otodynamics Analyzer. Results indicated that 1. In these cases there was no
correlation between the frequency of tinnitus and SOAE. 2. In 94.8% of
sensorineural hearing loss with tinnitus the DPOAE-gram presented lower amplitude
or was absent within the frequency range of elevated pure-tone-thresthold; In 59%
of cases with normal hearing and tinnitus the amplitude of DPOAE at nearby
frequencies of tinnitus was decreased and there was no SOAE detectable. At
frequencies other than that of tinnitus, the amplitude of DPOAE was normal and
SOAE could be recorded. So OAE could reflect cochlear lesion in early stage.
PMID- 9642351
TI - [Further comment on surgical approach for hemifacial spasm].
AB - A new surgical approach for the treatment of hemifacial spasm was carried out in
110 cases from 1991-1994. The novelty of this new procedure lies in splitting of
facial nerve by making multiple cuts along the long axis of the nerve-
descriptively a type of "combing". Among these cases, arachnoid thickening and
adhesion occurred in 35 cases throughout the vascular course, 66 cases showed
vascular compression (60%). A segment of vessel could be seen lying between VII
and VIII cranial nerves in 16 cases. Under the latter circumstance steps taken
for decompression would be either too risky or impossible. Postoperatively all
cases got marked improvement or total disappearance of symptoms & signs. Follow
up varying 1-4 years showed recurrence of symptoms in 6 cases (5.4%). This was
explaned in light of insufficient splitting. It might be due to lack of
experience or on account of vascular enclosures. It was suggested that at least
20 cuts should be made and tested with a minimum of 10mA electric stimulation to
achieve good result.
PMID- 9642352
TI - [Endoscopic sinus surgery for the treatment of inverted papilloma of nasal cavity
and paranasal sinuses].
AB - Fourteen patients suffering from inverted papilloma of the nasal cavity and sinus
were operated by the intranasal endoscopic approach. The period of follow-up were
24-60 months. Only one case had recurrence after three months and was then cured
by a combined treatment of external nasal approach and radiotherapy. The other 13
cases had no recurrence in the follow up period. The intranasal endoscopic
surgical technique was proved a better method for treating inverted papilloma of
nasal cavity and sinus even when the lesions had affected the posterior ethmoid
and spenoidal sinuses. It seems that this approrch would be a new way for
removing inverted papilloma completely and the major advantage of which is an
incision of the face can be avoided, while the curative rate might be the same or
even better than that of the external approach.
PMID- 9642353
TI - [Computed tomography of the ethmoid labyrinth and adjacent structures].
AB - In order to study the relation of ethmoid labyrinth to the adjacent structures,
continuous axial CT scan of the ethmoid labyrinth was performed on 9 normal
subjects. Meanwhile, coronal and axial CT scans of ethmoid labyrinth were
obtained in 20 normal subjects. On an average, 22 scan sections were done on each
subject. The relation of ethmoid labyrinth to adjacent structures was observed
and the remarkable intersubject variations in this anatomic area were noted. The
relation of posterior ethmoid cells or sphenoid sinus to the optic canal, and the
relation of internal carotid artery to the sphenoid sinus were clearly
demonstrated on axial scans. The detailed anatomic structure of the ostiomeatal
complex and the anatomic relation of ethmoid labyrinth to orbit and anterior
skull base were revealed by coronal CT scans. CT scan of the paranasal sinuses
was of great importance in clinical practice for the purpose of etiological
analysis of sinusitis, design of endoscopic sinus surgery and prevention of
complication.
PMID- 9642354
TI - [Current status and prospect of transnasal pituitary tumor operation and cranial
base surgery].
PMID- 9642355
TI - [Transseptal re-operation for recurrent pituitary adenoma].
AB - To summarize the suitable approach for recurrent pituitary adenoma, fifteen
patients with recurrent pituitary adenoma were re-operated via the transseptal
sphenoid approach for the second time. During the operation, some degree of
adhesion was noted in septal mucous membrane. The sphenoid cavity was filled with
fibrous tissue which has correlated to the methods of reconstructing sellar floor
during the previous operation. Follow-up study showed satisfactory results. It
showed that transseptal sphenoid re-operation is still the best approach for
treating recurrent pituitary adenoma in spite of some degree of operative
difficulties.
PMID- 9642356
TI - [Application of nasal endoscopy and cryosurgery in transsphenoidal removal of
pituitary tumors].
AB - In order to sum up the experience of transsphenoidal resection of pituitary
tumors, 60 cases operated between 1984 and 1995 were reviewed. The operation was
performed via a columella nasi "V" incision and transseptal-sphenoidal approach.
0 degree and 30 degrees endoscopes were used in 16 cases and the cryotherapy was
used to destroy the remnant tumor cells in 51 cases. The duration of freezing was
only one minute each time and it was repeated once again after thawing. The
advantages of this method were as follows: (1) wider operative field and better
illumination; (2) magnified operative pictures and TV monitoring; (3) wide and
changeable visual angle; (4) lack of complications such as hemorrhage, optic
nerve injury, permanent diabetes insipidus. The proper applications of endoscopy
and cryosurgery were recommended for transsphenoidal removal of pituitary tumors.
PMID- 9642358
TI - [Resection of cranial base tumors].
AB - This article reports 10 cases of cranial base tumors resected by pre-or retro
auricular intratemporal approach. Among them four were neuronomas, two
meningiomas, one malignant giant cell tumor of bone, one osteochondnoma, one
parotid mixed neoplasm and one poorly-differentiated squamors cell carcinoma.
Total resection in 9 cases and one subtotal resection were performed without
operative mortality and serious surgical complications. The surgical management
of cranial base tumor and indications for selecting operative approaches were
discussed.
PMID- 9642357
TI - [Transsphenoidal microsurgery for pituitary adenoma: analysis of 3 fatal cases].
AB - To prevent severe postoperative complications and increase the survival rate of
patients with pituitary adenoma after transsphenoidal microsurgery, 3 fatal cases
were analysed in terms of clinical features and caused of death. They included
(1) the too deeply inserted suction apparatus with resultant midbrain damage; (2)
bleeding from residual tumor into aphragma sellae and dura mater, entering the
subarachnoid, causing spasm of the brain vessels. In order to avoid complication,
it is necessary to follow strictly the rules for transsphenoidal microsurgery and
improve surgical skills.
PMID- 9642359
TI - [Effects of growth factors on the survival status and the neurite regeneration of
auditory neurons in vitro].
AB - To confirm the biological effects of peptide growth factors on auditory neuron
(AN) in vitro, the influence of NFG and bFGF on the survival status and the
neurite regrowth of dissociated primary AN in postnatal chicks was studied with
serum-free culture technique and cytologic quantitative method. The results
demonstrated that the growth of non-neuron elements such as Schwann's cell was
predominant in the earlier stage of culture. The neurite regrowth (bipolarity or
unipolarity) of AN was observed at 24 hours after seeding. The growth rate
increase during 48-72 hours in the surviving AN. These findings indicated that
both growth factors exerted direct neuronotrophic effect on dissociated AN in
vitro. NGF and bFGF acted in cooperation to promote the axon regeneration of AN.
The concentration-dependent effect of NGF on neurite regrowth and neurone
survival was found in the present study. The biological mechanism of NGF and bFGF
on AN in vitro has been discussed.
PMID- 9642360
TI - [Effects of ATP on intracellular free [Ca2+]i in isolated cochlear OHC].
AB - The effect of adenosine triphosphate (ATP) upon intracellular free calcium
concentration ([Ca2+]i) of cochlear outer hair cell (OHC) isolated from guinea
pigs was studied. Stained with fluorescence, [CA2+]i was measured using ACAS 570.
ATP significantly increased the [Ca2+]i level, which then dropped rapidly from
the peak value it rose again reaction after readdtion of ATP. This result
indicates that ATP is a nerve transmitter acting on the outer hair cells.
PMID- 9642361
TI - [Experimental study of streptomycin on 45Ca intake of otolithic membranes].
AB - 45CaCO3 was injected into guinea pigs, and the radioactivity in otolithic
membranes of utriculi and sacculi, auditory ossicles and femora was determined by
liquid scintillation spectrometry, to study the dynamic effect of streptomycin on
calcium content of otolithic membranes, as a means to explore the mechanism of
streptomycin ototoxicity. The results showed that otoconium was a dynamic
structure which took up 45Ca in a time course generally comparable to that of
bone. Saccular otolithic membranes showed greater intake than utricular
membranes. The calcium ion concentration of saccular endolymph was greater than
that of the utriculus and the two maculas were not identical. Streptomycin may
influence 45Ca uptake in the two macular otolithic membranes, causes calcium
metabolic disorder and a fall of otolithic calcium content. It is possible that
the fluid environments of the endolymph have changed, therefore dysfunction of
otolithic organ may occur. This hypothesis may be one of the explanation of the
mechanism of streptomycin ototoxicity.
PMID- 9642362
TI - [The effect of MPS on LAK cell growth and its cytotoxic activity against
laryngeal cancer (HEP-2)].
AB - IL-2/LAK adoptive immunotherapy is one of new complementary treatments for
advanced malignant tumors. This therapy has two main problems: high dose of IL-2
often causes serious side effects and it is difficult to gain enough amount of
LAK cells. MPS is a new immunomodulator in cancer immunotherapy. The present
study showed that, comparing with IL-2 10(6)U/L only, IL-2 2 x 10(5)U/L plus MPS
0.4mg/L was significantly more effective in activating both the growth of LAK
cells and its cytotoxicity against HEP-2 cells. And the ratio of CD25 positive
LAK cells cultured in this condition was also higher. This result suggests that
MPS plays a role in creasing the membrane receptors of IL-2.
PMID- 9642363
TI - [Histopathology of the temporal bone in adhesive otitis media].
AB - To understand the histopathological changes of adhesive otitis media (AOM) in
human, temporal bone sections processed with the celloidin-embedding technique
were reviewed. In the 338 pairs of temporal bone specimens, 20 cases (26 ears)
showed characteristics of AOM. The results showed that the lesions of AOM were
extensive, involving all middle ear structures including tympanic muscles, round
and oval windows. There were various pathological changes, in every stage of
inflammation and tissue repair. According to the main pathological
characteristics, histopathological changes of the 26 ears were staged as
exudation, inflammatory grannlation formation, histocyte response and collegen
proliferation. As the process progressed, the amount of inflammatory cells and
exudate decreased with the increase of fibroblasts. Certain factors were
speculated to play an important role in the process of fibrosis. The authors
analysed the difficulties in the management of AOM and causes of the
unsatisfactory therapeutic results. Possible measures to improve treatment
results were proposed.
PMID- 9642364
TI - [Clinical application of enzyme linked immunosorbent assay in testing antibodies
against cochlear tissues and nerve tissues].
AB - Fifty-two patients with idiopathic sensorineural hearing loss and 20 controls
were examined by enzyme linked immunosorbent assay (ELISA) with cow cochlear
antigen (CCAg) and cow cochlear nerve antigen (CCNAg). The antibody level against
CCAg was 0.3811 +/- 0.743 in the control group and 0.9241 +/- 0.2408 in the
experimental group (OD, x +/- 2s, P < 0.01). Compared with the x +/- 2s antibody
level of the control group, the antibody level of 24 of 52 (46%) patients of the
experimental group was positive. The antibody level against CCNAg was 0.2254 +/-
0.382 in the control group and 0.2331 +/- 0.656 in the experimental group (P >
0.05). Compared with the x +/- 2s antibody level of the control group, the
antibody level of 6 of 52 patients (11.5%) of the experimental group was
elevated. It is suggested that ELISA method can be used as quantitatively in the
diagnosis of autoimmune inner ear diseases. Moreover, the serum antibodies
against CCNAg detected in this experiment suggest that some of autoimmune inner
diseases might be retrocochlear.
PMID- 9642365
TI - [CT study of the ostiomeatal complex in patients with deviated nasal septum].
AB - This study was designed to evaluate the influence of nasal septal deviation on
ostiomeatal complex (OMC). From April 1994 to February 1995, 32 patients with
deviated nasal septum were investigated by high-resolution CT scan. The results
showed that (1) 15 patients (15/32) were found to have ipsilateral or bilateral
ostiomeatal complex disease (OMCD). The incidence of OMCD was related to the
severity of the septal deviation; (2) measurement of uncinate process angulation
and ethmoid infundibulum width in patients with OMCD was of limited value; (3)
the relationship between septal deviation and OMC variation needed further study.
It has been indicated that for patients with septal deviation coronal CT study is
necessary to evaluate the degree of OMCD.
PMID- 9642366
TI - [Outpatient treatment of obstructive sleep apnea syndrome with CO2 laser: laser
assisted uvulopalatoplasty].
AB - To find a safe and convenient method for the treatment of obstructive sleep apnea
syndrome, 89 outpatient cases were treated with CO2 laser-assisted
uvulopalatoplasty. All cases had been diagnosed and observed with
polysomnographic monitoring. The result of 89 cases of OSAS was judged as good in
67 cases (75.7%). Only 6 cases had a little bleeding during operation, no other
complication has been encountered.
PMID- 9642367
TI - [Longitudinal evaluation of vocal function following thyroplasty type I for the
treatment of unilateral vocal paralysis].
AB - Longitudinal changes of vocal efficiency and stability following thyroplasty type
I were analysed. Fifty-three patients with unilateral vocal fold paralysis
underwent vocal function evaluation preoperatively and 1, 3 and 6 months
postoperatively. Vocal function assessment included videostrobolaryngoscopic
examination, acoustical and aerodynamic analyses, and perceptual ratings of
voice. Parameters including glottic gag size, maximum phonation time, glottic
flow rate, jitter, harmonic to noise ratio, breathness, hoarseness, loudness and
phrasing showed significant improvement after thyroplasty and remained stable
within 1 month with only slight fluctuations over a 6 month period. Postoperative
voice outcome was not affected by age, sex, duration of vocal symptoms, etiology
of paralysis, or preoperative pulmonary function.
PMID- 9642368
TI - [A study of LOH on chromosome 9p21 region D9S319 locus of laryngeal carcinoma].
AB - Loss of Heterozygosity (LOH) on chromosome 9p21 (D9S319) from fifty-four
laryngeal cancer patients has been examined by using the PCR technique of DNA
microsatellite markers in this study. The results showed that the LOH on 9p21 was
100% present (2/2) in in situ carcinomas and 66% (29/44) in invasive carcinomas.
Therefore, these results suggest that there is a tumor suppressor gene located on
9p21 region. Its inactivation was related to laryngeal carcinoma and it was an
early event.
PMID- 9642369
TI - [Treatment and results of N1 supraglottic laryngeal carcinoma].
AB - One hundred and eleven cases of supraglottic squamous cell cancer (T1-4N1) were
retrospectively analysed. The result showed that: 1. the 3 years survival rate
was 72% (80/111); 2, the rate of contralateral neck node metastasis after
ipsilateral RND was 17.9%, and the cases of T3-4 with positive histologic
findings of neck dissection samples had a higher rate contralateral neck node
metastasis (38.6%); 3, the contralateral neck node metastasis rate (26.1%) in the
group with surgery alone was significantly higher than that (7.1%) in the group
with preoperative radiation (P < 0.05). The authors draw the conclusion that
contralateral neck node metastasis is a high risk factor for recurrence of N1
supraglottic laryngeal cancer and that preoperative radiation may be be useful in
controlling subclinical metastasis.
PMID- 9642370
TI - [Current status and prospects of the study on autocrine and paracrine regulation
of ovarian function].
PMID- 9642371
TI - [The secretion and receptor gene of insulin-like growth factor-I quantitative
expression in ovarian stroma in polycystic ovarian syndrome patients].
AB - OBJECTIVE: To explore varying different degrees of the action of insulin-like
growth factor-I (IGF-I) and its receptor gene quantitative expression in the
ovarian stroma of women with obese and nonobese polycystic ovarian syndrome
(PCOS). METHOD: The expression of IGF-I receptor gene in the ovarian stroma from
35 cases of PCOS (obese: 15 cases; nonobese: 20 cases) and 20 cases of control
were quantitatively determined by reverse transcript polymerase chain reaction
(RT-PCR) combined with beta(2) micro globlin (beta(2) MG) gene as inner-control
to amplificate sychronously. The grey value ratio of them were determined. The
PCR-amplified cDNA fragments were put in restriction analysis (DdeI). RESULTS:
The expression of IGF-I receptor in PCOS ovary stroma was significantly greater
than in the control group (P < 0.001). The nonobese group presents more
enhancement than obese group in IGF-I receptor gene expression. The restrictive
fragments were same between the PCOS and the control group. CONCLUSIONS: The
expression of IGF-I receptor in PCOS ovarian stroma is abnormally excessive and
the nonobese PCOS have more potential action of IGF-I system in ovary stroma.
PMID- 9642372
TI - [Experimental study on the effect of insulin-like growth factor-I on maturation
fertilization and cleavage of murine oocytes in vitro].
AB - OBJECTIVES: To evaluate the effects of insulin-like growth factor-I (IGF-I) on
the maturation, fertilization, and cleavage of murine oocytes. METHODS: Immature
and mature murine oocytes were cultured alone or together with murine spermatozoa
in vitro. Various concentrations of IGF-I were added to the media as experimental
groups, and was not added as controls. Then the rates of maturation,
fertilization and cleavage of murine oocytes were observed, and compared between
the 2 groups. RESULTS: The rates of maturation, fertilization and cleavage of
murine oocytes in experimental groups were significantly higher than those in the
controls (P < 0.01 or P < 0.05). Unequal blastomeres and cell fragments were
observed in both groups, but the differences during the same cultured period were
not statistically significant (P > 0.05). CONCLUSIONS: IGF-I could induce murine
oocyte maturation, promote its fertilization and cleavage in vitro, and do no
harm to the fertilized oocytes and embryos.
PMID- 9642373
TI - [Application of ultra-short gonadotropin-releasing hormone agonist protocol in
controlled ovarian hyperstimulation].
AB - OBJECTIVE: To study the effect of the ultra-short protocol of gonadotropin
releasing hormone agonist (GnRH-a) combined with human menopausal gonadotropin
(hMG) regimen for ovarian hyperstimulation. METHODS: Setting clomiphene
(CC)/human chronic gonadotropin (hCG) (50 cycles, 31 patients) and CC/hmg/hCG
regimens (16 cycles, 16 patients who had failed in CC/hCG) as control groups, the
ultra-short GnRH-a/hMG/hCG regimen (15 cycles, 15 patients who had failed in CC
alone or CC/hMG regimens) as study group, the number of leading follicles,
endometrial thickness, cervical mucus scores and hormone levels on the day of hCG
administration, and the pregnancy rates were compared among of these three
groups. RESULTS: There was no premature luteotropic hormone (LH) surge in the
ultra-short GnRH-a/hMG/hCG regimen group while there were three cycles in the
CC/hMg/hCG group. The LH and progesterone (P) levels of ultra-short GnRH-a/hMG
group on the day of hCG administration were lower than those of CC alone and
CC/hMG groups. There were more leading follicles, greater endometrial thickness
and cervical mucus score in the ultra-short GnRH-a/hMG group than those in CC
alone and CC/hMG groups. The pregnancy rates per cycles in the three groups were
similar. CONCLUSION: The ultra-short GnRH-a/hMG regimen is a fairly good ovarian
hyperstimulation regimen, especially for poor responders in CC alone or CC/hMG
regimens.
PMID- 9642374
TI - [Expression of transforming growth factor-alpha and myc oncoprotein in the human
ovary during follicular growth, atresia and corpus luteum formation regression].
AB - OBJECTIVE: To investigate the expression of transforming growth factor (TGF)
alpha and myc oncoprotein on human follicular development and atresia in vitro.
METHODS: Ovarian tissues were obtained from 36 women with regular menstrual
cycles who underwent abdominal hysterectomy for a variety of gynecological
conditions. Expression of TGF-alpha and myc protein in the ovarian tissues was
examined by immunohistochemical technique. RESULTS: In primordial follicale only
the oocyte showed intense immunostaining for both TGF-alpha and myc oncoprotein.
Immunostaining for TGF-alpha in granulosa cells and theca interna cells became
apparent in the follicles of preantral stage. With the increase in the size of
follicles the intensity of immunostaining in the oocyte decreased, whereas the
staining intensity of the granulosa and theca cells increased, and persisted in
the corpus luteum and further intensifying during the midluteal phase. myc
protein expression in granulosa cells was apparent only in the preantral follicle
stage. In the regressing corpus luteum, expression of both TGF-alpha and myc
oncoprotein was restricted only in the peripheral theca lutein cells adjacent to
the central core of scar issue. In atretic follicles theca interna cells
exhibited prominent immunostaining for TGF-alpha and myc protein. CONCLUSION: TGF
alpha and myc oncoprotein combination play a role as intraovarian regulators
through autocrine and paracrine mechanism and may participate in remodelling the
initial growth of the oocyte, follicular growth, differentiate and apoptosis.
PMID- 9642375
TI - [The comparison of clinical and surgical-pathological staging for endometrial
carcinoma].
AB - OBJECTIVE: To compare the differences between clinical (FIGO 1971) and surgical
pathological (FIGO 1989) stagings of endometrial carcinoma and to investigate the
advantage and the feasibility of the surgical-pathological staging. METHODS:
Clinical and pathological data of 290 patients with endometrial carcinoma
surgically treated from 1989 to 1995 were retrospectively reviewed. The clinical
and surgical-pathologic staging of these patients were compared. The stagings
were analyzed with regards to the prognostic factors of endometrial cancer.
RESULTS: The differences between clinical and surgical-pathologic staging in
stage I and II were 19.7% and 80.5% respectively. 4.2% with metastases to the
lymph node, 10.6% with positive peritoneal cytology and 60.5% with myometrial
invasion were found in clinical stage I. 51.4% with metastases to the lymph
nodes, 46.9% with positive peritoneal cytology and 100.0% of myometrial invasion
were observed in clinical stage II. The causes of the differences between these
two staging systems are: (1) it was impossible before operation to accurately
detect metastases of the lymph nodes and malignant cells in the pelvic-peritoneal
cavity; (2) when the dilation and curettage was done before operation, the
lesions of an involved cervix might be missed or an uninvolved cervix
misdiagnosed as metastatic lesion; (3) there were already cancer cells
disseminated in the peritoneal cavity. CONCLUSIONS: The surgical-pathologic
staging defines the real extent of endometrial carcinoma. It is advised that at
the initial operation attention should be paid to areas beyond the extent of the
intended surgery itself. During the initial operation, peritoneal cytology and
pelvic and para-aortic lymph node samplings should be done for the purpose of
surgical-pathologic staging of the selection of postoperative adjuvant therapy
and of providing a clinico-pathological basis for the prediction of prognosis.
Since there is a high percentage of misdiagnosis in clinical stage II endometrial
carcinoma, special attention is needed in diagnosing and treating such patients.
PMID- 9642376
TI - [Therapeutic modalities of endometrial carcinoma in stage I and II].
AB - OBJECTIVE: To evaluate the effectiveness of different therapeutic modalities of
endometrial carcinoma in stage I and stage II. METHODS: From 1984 to 1992, 205
patients with endometrial carcinoma in stage I and stage II were treated in our
hospital. The clinical and pathological data were analyzed retrospectively. There
were 122 cases in stage I and 83 in stage II. According to therapeutic methods,
patients could be divided into 4 groups. Group 1 (surgery group): 81 cases; Group
2 (full dose preoperative intracavitary afterloading irradiation, A point 45G y
+/- 10%, F point 50 Gy +/- 10%): 62 cases; Group 3 (non-full dose preoperative
intracavitary afterloading irradiation, doses at both point A and point F less
than 1/2 of full dose mentioned above): 36 cases; Group 4 (radiotherapy alone):
26 cases. There were no significant differences in pathological type,
differential grade, median age and operative methods among the 4 groups. RESULTS:
The 5-year survival rate of group 1 to group 4 was 83.1%, 96.5%, 84.8% and 62.5%
respectively in stage I, and 82.0%, 90.9%, 51.4% and 62.7% respectively in stage
II. The 5-year survival rate was significantly higher in group 2 (P < 0.05).
CONCLUSIONS: The results suggested that operation combined with full dose
preoperative intracavitary afterloading irradiation provided the best therapeutic
effect, whereas non-full dose preoperative intracavitary afterloading irradiation
showed none of benefit.
PMID- 9642377
TI - [The relationship between the pathologic features of the uninvolved endometrium
and prognosis in postmenopausal endometrial carcinoma].
AB - OBJECTIVE: To investigate the relationship between the pathologic features of the
uninvolved endometrium and prognosis in postmenopausal endometrial carcinoma.
METHOD: The clinicopathologic features of 204 cases of endometrial carcinoma were
analyzed retrospectively, according to the proliferative and atrophic uninvolved
endometrium, a long term follow-up was done. RESULTS: The patients with
proliferative uninvolved endometrium (PUE) were more much related with the
clinical risk factors than those of atrophic uninvolved endometrium (AUE) (P <
0.001). AUE cases had more virulent types of nonendometrial carcinoma than those
of PUE (27% vs 5.5%, P < 0.001), and had much worse grade, much deeper myometrial
invasion and much vascular invasion (P < 0.001). The overall 5-year survival rate
was 96.7% in the PUE cases and 86.2% in the AUE cases (P < 0.001). CONCLUSION:
The histopathologic types of the uninvolved endometrium were related to the
prognosis of the patients with endometrial carcinoma. The patients with
proliferative uninvolved endometrium had better prognosis than those with
atrophic uninvolved endometrium.
PMID- 9642378
TI - [Human leucocyte antigen-DQA1, -DQB1 polymorphism distribution in Shanghai
Chinese women with pregnancy induced hypertension].
AB - OBJECTIVE: To explore the mechanism of correlation between human leucocyte
antigen (HLA) and pregnancy induced hypertension (PIH). METHODS: Oligotyped HLA
DQA1, -DQB1 locus in 30 Shanghai Chinese PIH families and 14 control families
were analysed by polymerase chain reaction-sequence specific oligonucleotide (PCR
SSO) hybridization method (probes labelled by nonradioactive technique). RESULTS:
Compared with the control group, the allelic frequency of HLA-DQB1 * 0502 was
significantly higher in PIH couples, and their sharing of HLA-DQA1 increased. No
difference was found in HLA-DQA1 allelic frequency or HLA-DQB1 sharing in couples
of the two groups. Analysis of HLA-DQA1 and DQB1 allelic frequency in PIH
patients and their neonates showed no positive results. CONCLUSION: HLA-DQB1 *
0502 may be the marker of susceptibility to PIH. The increase of compatibility in
HLA-D region resulted in decrease of producting blocking antibody. The unbalance
of maternal-fetal immunity will induce PIH.
PMID- 9642379
TI - [Oral low-dose magnesium gluconate preventing pregnancy induced hypertension].
AB - OBJECTIVE: To study the effects of oral low-dose magnesium gluconate in
prevention of pregnancy induced hypertension (PIH) and its mechanism. METHODS: A
prospective randomized double-blind study was carried out in 51 pregnant women as
treatment group (including 22 cases as treatment group 1 and 29 cases as
treatment group 2) and 51 pregnant women as controls (including 28 cases as
controls group 1 and 23 cases as control group 2). Low-dose magnesium gluconate
(3 g/day) or placebo was given from the 28th week of gestation to delivery
consecutively. RESULTS: 4% of the pregnant women developed PIH after magnesium
gluconate treatment, which was substantially lower than that in the control group
(16%) (P < 0.05). In the treatment group 2, women showed higher concentration of
6-keto-prostaglandin F1 alpha (PGF1a) and 6-keto-/thromboxane B2(TXB2) (P/T)
ratio than that of the control group 2. Moreover, TXB2 level was lower than that
in the control group 2. In the treatment group 1 women showed higher ratio of P/T
than that of the control group 1. There were no significant differences of serum
magnesium concentration among all groups. CONCLUSION: Low-dose magnesium
gluconate may efficiently prevent PIH in high risk women. The mechanism of action
of magnesium gluconate probably involves to keep the balance of PGI2 and TXA2,
but not associates with serum magnesium level.
PMID- 9642380
TI - [Glycosylated high density lipoprotein in diabetes related to pregnancy induced
hypertension].
AB - OBJECTIVE: To investigate the glycosylation of high density lipoprotein (glc-HDL)
and its specific binding to human lung fibroblasts (HLF) receptors in gestational
diabetes woman and to study its relationship with pregnancy induced hypertension
(PIH). METHODS: The glc-HDL was measured by fluorimetry and the specific binding
of HDL to HLF receptors was measured with enzyme linked immunoreceptor assay in
32 gestational diabetic woman group 1, 34 group II, 36 normal pregnant (NP) and
32 normal non-pregnant (NNP) women. RESULTS: The levels of glc-HDL and the
intracellular total cholesterol in diabetic pregnant woman group I and II were
significantly higher than those in the NP and the NNP (P < 0.01). The cell
binding, internalization and degradation of glc-HDL were higher than that in the
NP and the NNP. CONCLUSION: The change of HDL level and lipid deposition during
the process may be one of the causes for arteriole spasm in PIH.
PMID- 9642381
TI - [The characteristics of labour course and perinatal prognosis in cases of fetal
persistent occiput-transverse position and persistent occiput-posterior
position].
AB - OBJECTIVES: To study the characteristics of the labour course and perinatal
prognosis in cases of fetal persistent occiput-transverse position (POTP) and
persistent occiput-posterior position (POPP). METHODS: All the cases, delivered
with POTP and POPP in or hospital from Nov, 1995 to July 1996 were analyzed
retrospectively. RESULTS: In abnormal fetal occipital position group, the
following indices were significantly higher than those of normal group: fetal
macrosomia, uterine inertia, and duration of each labour course. The speed of
descending of presentation was obviously slower. The incidence of abnormal labour
course was markedly increased. The rate of operative delivery was significantly
higher. The total rate of operative delivery was 82.81% in the POTP group, and
92.31% in the POPP group. The incidence fetal hypoxia and neonatal asphyxia was
markedly high in the abnormal occiput group. CONCLUSIONS: The POTP and POPP are
major cases of dystocia. If management is unsuitable, perinatal prognosis will be
poor.
PMID- 9642382
TI - [Relation between fetal intrauterine growth retardation and anticardiolipin
antibodies].
AB - OBJECTIVE: To investigate the relationship between fetal intrauterine growth
retardation and anticardiolipin antibodies. METHODS: Serum anticardiolipin
antibodies were detected with ELISA method in 5,330 cases of normal gravidas.
Meanwhile, the observation of immunocomplex depositions in placentas in cases of
positive anticardiolipin antibodies (ACA) were observed by immunofluorescence
examination. RESULTS: The positive ACA rate in normal gravidas was 2.70%. The
incidence of intrauterine growth retardation (IUGR) was 15.28% in cases of
positive ACA, whereas was 1.77% in cases of negative ACA. There were significant
differences between two groups (P < 0.001). Among children born in mothers with
positive ACA, there were 5 cases of positive ACA. Immunocomplex depositions
(Immunoglobulins & Complements) were all found in placenta of IUGR. CONCLUSIONS:
ACA could be one of causes of IUGR. Determination of serum ACA would offer a new
clue to diagnosis and treatment of IUGR.
PMID- 9642383
TI - [Gonadotropin and autocrone mediated regulation of the ovary].
PMID- 9642384
TI - [Application of computer in obstetrics].
PMID- 9642385
TI - [On the conservation and regeneration of Taxus resources].
AB - In recent years, the taxol isolated from the stem bark of some plants of Taxus
has been widely as an antitumor agent. But the development of taxol is limited by
the scarcity of wild Taxus resources. This paper seeks to discuss the ways to
conserve and promote the regeneration of these resources.
PMID- 9642386
TI - [Application of adaptive resonance theory network to the quality evaluation of
radix Sophorae flavescentis].
AB - ART1 and ART2 models of adaptive resonance theory network have been employed in
quality evaluation of 40 Radix Sophorae Flavescentis samples collected from
different regions of China. Based on the UV data of MeOH extract and IR data of
CHCL3 extract, Shannon information theory has been used for feature selection.
The results consist with those of traditional appraisal.
PMID- 9642387
TI - [Analysis and identification of calculus equi components].
AB - Components of the genuine calculus Equi and false Mabao were analyzed by X-ray
diffraction. The results indicate that the main components of the genuine Mabo
are NH4MgPO4.6H2O, NH4MgPO4.H2O and MgHPO4.3H2O, whereas the main components of
the false Mabao is CaCO3.
PMID- 9642388
TI - [Influence of processing on quercetin content in flos Sophorae immaturus].
AB - The HPLC method was applied to determine the quercetin content in Flos Sophorae
Immaturus. The technology for processing Flos Sophorae Immaturus was selected
based on orthogonal experiment design. The result has shown that the better
technology is to bake Flos Sophorae Immaturus for 11 min at the temperature of
180 degrees C.
PMID- 9642389
TI - [Effect of processing of the contents of pinoresinol diglucoside in cortex
Eucommiae].
AB - The contents of pinoresinol diglucoside in different processed products of Cortex
Eucommiae were determined by HPLC. The result has shown that the contents of
pinoresinol diglucoside in post-processed drugs are higher than those in pre
processed ones.
PMID- 9642390
TI - [Changes of chemical constituents of radix Sophorae flavescentis in complex
formulas of traditional Chinese medicine].
AB - Experiments have been made on the changes of chemical constituents in complex
formulas of traditional Chinese medicine. The results show that in the complex
formula containing Radix Sophorae Flavescentis, as affected by various conditions
of processing such as water, temperature and coexisting reductive substances, the
content of oxymatrine tends to decrease gradually to disappear while that of
matrine increase gradually.
PMID- 9642391
TI - [Water soluble contents of Chinese drug beimu, the bulbs of Fritillaria plants].
AB - Based on platelet aggregation induced by platelet activating factor (PAF), the
active fraction with inhibiting effect was screened from four species of Chinese
drung Beimu, the bulbs of Fritillaria przewalskii, F. ussurienis, F. anhuiensis
and F. thunbergii. According to the experimental results, the active water
soluble fraction of F. ussuriensis was further studied. Two nucleosides,
thymidine and adenosine were isolated. Platelet aggregation assay shows that
adenosine is the chief aggregation inhibitor with 1% = 42 at 5 microns. It is
suggested that nucleosides may be the other type of active constituent besides
alkaloids in the Fritillaria plants.
PMID- 9642392
TI - [Chemical composition of Craibiodendron henryi W. W. Smith].
AB - Two components were isolated from the dried leaves of Craibiodendron henryi and
identified as rhodojaponin II and III by means of IR, MS, 1HNMR and 13CNMR
spectra. These two compounds are obtained from the herb for the first time.
PMID- 9642393
TI - [Chemical studies on the root of Salvia trijuga Diels].
AB - From the root of Salvia trijuga three triterpenoids were isolated. Based on the
analysis of their spectra, they were identified as coleonolic acid with a
contracted A-ring, euscaphic acid and 2 alpha-hydroxyursolic acid.
PMID- 9642394
TI - [Chemical constituents of Ligusticum brachylobum Franch].
AB - From the roots of Ligusticum brachylobum, which is used as a substitute for
traditional Chinese medicine Radix Peucedani in the southwest of China, 5
compounds were isolated and identified as umbelliferone, selinidin, anomalin,
nodakenin and ferulic acid.
PMID- 9642395
TI - [Chemical constituents of the root of Boehmeira nivea (L.) Gaud].
AB - Three compounds were isolated from the root of Boehmeria nivea and elucidated
according to their spectroscopic data as beta-sitosterol, daucosterol and 19
alpha-hydroxyursolic acid. They are obtained from the herb for the first time.
PMID- 9642396
TI - [Determination of loganin in the fruit of Cornus officinalis Sieb. et Zucc].
AB - A high performance liquid chromatographic method has been developed for the
determination of loganin in the fruit of Cornus of ficinalis. The method is
rapid, accurate and sensitive.
PMID- 9642397
TI - [Effects of ginsenosides from stems and leaves on hyperlipemia induced by
prednisone acetate in rabbits].
AB - Rise of total lipid, total cholesterol and triglyceride in rabbits were markedly
inhibited by oral administration of ginsenosides from stems and leaves at a daily
dose of 60mg/kg. The inhibitory rates were 66.2%, 92.8% and 58.1% respectively.
PMID- 9642398
TI - [Effects of saponins from stems and leaves of Panax quinquefolium L. on the
contraction of rabbit aortic strips].
AB - It has been found out that the saponins from stems and leaves of Panax
quinquefolium (PQS) can non-competitively antagonize the dose-response curves of
norepinephrine (NE), potassium chloride and calcium chloride on the isolated
aortic strips of rabbits, and obviously inhibit intracellular and extracellular
Ca2(+)-dependent contraction of the aortic strips induced by NE. These effects of
PQS are similar to verapamil.
PMID- 9642399
TI - [Spasmolytic effects of crebanine on isolated gallbladder and Oddi's sphincter in
vitro].
AB - The study has shown that the contraction induced by histamine, Ca2+ and K+ in the
biliary system of guinea-pigs is antagonized by crebanine in vitro. The
antagonism presents a depression of the maximal response of the dose-response
curve for the agonists in a non-competitive manner. Crebanine blocks the release
of calcium from intracellular storage on isolated gall-bladder. The spontaneous
activity of the oddi's sphincter in vitro is inhibited by crebanine. The initial
phasic and the ionic contraction induced by K+ (40 mmol/L) in the isolated oddi's
sphincters of guinea-pigs are inhibited by crebanine.
PMID- 9642400
TI - [Comparison between Cistanche deserticola Y. C. Ma and C, tubulosa (Shenk) Wight
on some pharmacological actions].
AB - The weights of seminal vesicle and prostate gland of castrated young rats were
significantly increased by administration of alcohol soluble extract from the
decoction of Cintanche deserticola, C. tubulosa and soaked C. deserticola. The
phagocytic function of intra-abdominal macrophage in mice was activated by the
decoction of C. deserticola and C. tubulosa.
PMID- 9642401
TI - [Compatibility of toxic Chinese medicines].
AB - This article expounds the suitable compatibility and incompatibility in using
toxic Chinese medicines in respects of reducing toxicity, raising curative
effect, enhancing toxicity and reducing curative effect. Meanwhile it discusses
the compatibility mechanism of toxic Chinese medicines in combination with the
studies of clinical and modern experiments.
PMID- 9642402
TI - [Folk medicine of the Qiang nationality].
AB - Based on a two-year investigation of folk medicine of the Qiang Nationality,
systematic studies have been made on its formation and development, specific
methods of physical therapy and experiences and features of clinical application.
PMID- 9642403
TI - [Detection of konjac glucomannan in seven Amorphophallus Blume species].
AB - Seven Amorphophallus species were detected for konjac glucomananam (KGM). It has
been found out that A. albus, A. konjac, A. yuloensis, A. xemengensis and A.
dunnii are of higher contents of KGM (30%), but A. sinensis and A. yunnanensis
are not as further comfirmed by TLC analysis. It follows that A. albus, A.
konjac, A. yuloensis, A. xemengensis and A. dunnii are high quality resources of
KGM, but A. sinensis and A. yunanensis cannot be used as substitutes for the
above-cited five species.
PMID- 9642404
TI - [Rules of the absorption, distribution and translocation of nitrogen, phosphorus
and potassium in turmeric plant].
AB - It has been found out that the percentages of nitrogen (N), phosphorus (P) and
potassium (K) in turmeric plant (Curcuma longa) are higher in young organs.
Varying with the growth stages, the nutrient contents of the plant, whose amount
order is K > N > P are the highest in the seedling stage. Nutrient absorption
occurs mainly in the young turmeric forming stage and enriching stage. Nutrient
translocation takes place mainly from leaves and leaf stalks to young and old
turmeric, the rate of P being the highest.
PMID- 9642405
TI - [Callus induction of Coptis species and generation of alkaloids].
AB - Callus induction and tissue culture of six medicinal Coptis species have been
carried out and a comparative analysis of berberine, jatrorrhizine, coptisine,
palmatine and epiberberine in calli and crude drugs have been made by TLC and
HPLC.
PMID- 9642406
TI - [HPLC analysis of mimic vinegar-processed yuanhuacine].
AB - In this paper, the variation of yuanhuacine samples after vinegar-processing and
hydrolysis has been analyzed by HPLC. The result has shown that the content of
yuanhuacine decreases hearly 22% after mimic vinegar-processing. Also this
procedure has brought a new compound-hydrolytic product of yuanhuacine, whose UV
lambda max is 264nm. The research work is to be continued.
PMID- 9642407
TI - [Selection of technology for processing steamed Garcinia hunburyi with high
pressure].
AB - The technology for processing steamed Garcinia hunburyi with high pressure was
synthetically selected by using orthogonal experiment design, based on the
indexes of anti-inflammatory, bacteriocidal, anti-tumour effects and gambagic
acid content. The result shows that the best way is to steam for 0.5 h at 126
degrees C.
PMID- 9642408
TI - [Comparison of 4 extraction methods for antidotal granules of Coptis].
AB - Four extraction methods for Antidotal Cranules of coptis were compared, with
berberine, barcalin and gardenoside taken as the indexes. The result shows that
the total contents of three components appear in the following order: semi-bionic
extraction > semi-bionic extraction with precipitation with alcohol > extraction
with water > extraction with water plus precipitation with alcohol.
PMID- 9642409
TI - [Chemical constituents of Eclipta alba (L.) Hassk].
AB - Ecliptasaponin C (1), a new triterpenoid glucoside, was isolated together with
daucosterol (2) and stigmasterol-3-O-glucoside (3) from Eclipta alba. Based on
spectral analysis, chemical evidence and hydrolytic results, it's structure was
deduced as 3-beta-O-beta-D-glucopyranosyl-19beta-hydroxy olean-12-ene-28-oic acid
28-O-beta-D-glucopyranoside, Compounds 2 and 3 were obtained from Eclipta for the
fist time.
PMID- 9642410
TI - [Chemical constituents of Aralia fargesii Franch].
AB - From the EtOH extract of Aralia fargesii, 8 compounds were isolated and
identified as umbelliferone, esculetin, scopoletin, scoparone, oleanic acid,
falcarindiol, mellissic acid and beta-sitosterol.
PMID- 9642411
TI - [Chemical constituents of Aster albscens Hand.-Mazz].
AB - Four compounds, stigmasterol, D-hurulon-14-en-3-ol, stigma-delta7.22-dien-3beta
palmitate and friedelin were isolated from the root of Aster albscens for the
first time. Their structures were elucidated by spectral methods.
PMID- 9642412
TI - [Determination of paeonol in the root of Cynanchum paniculatum (Bge.) Kitag. by
gas chromatography].
AB - A method for the determination of paeonol in the root of Cynanchum paniculatum by
macro-reticular resin-GC has been established. The experimental result shows that
the standard curve is linear in the detection range and the recovery is 99.42%
(RSD = 2.28%, n = 5).
PMID- 9642413
TI - [Determination of nodakenin in the rhizome or root of Notopterygium incisum Ting
by TLC-scanning].
AB - TLC-scanning was applied to the determination of nodakenin in the rhizome or root
of Notopterygium incisum from three different producing areas. The correlation
coefficient was 0.9997, recovery 97.5% and relative standard deviation 1.96%.
PMID- 9642414
TI - [Immunological regulation of rhizoma Imperatae on IL-2 and T-lymphocyte
subpopulation].
AB - The present study has proved that rhizoma imperatae can significantly raise the
phagocytic rate and index in experimental mice, as well as the number of T(H)
cells, and in the meantime facilitates the generation of interleukin-2. This
indicates that rhizoma imperatae is markedly conducive to the enhancement of
immunologic function of mice.
PMID- 9642415
TI - [Effects of ding zhi pills on the scopolamine-induced impairment of passive
avoidance in rats].
AB - The Ding Zhi Pills described in "Thousand-Golden-Prescriptions" have better
memory improving effect than those described in "Prescriptions People's Welfare
Pharmacy". A combination of Poria, Radix Polygalae and Rhizoma Acori Graminei
could enhance the pharmacologic effect of Radix Ginseng. Cinnabaris, described in
"Prescriptions People's welfare Pharmacy", as one of the compositions in Ding Zhi
Pills, does not improve the impairment of learning and memory, and therefore
seems to have no meaning in the Ding Zhi Pills.
PMID- 9642416
TI - [The Selaginella tamariscina (Beauv.) Spring complex in the treatment of
experimental diabetes and its effect on blood rheology].
AB - Experiments have revealed that in treating rats for diabetes induced by alloxan,
the Selaginella tamariscina complex injection given intraperitoneally (25g/kg)
for 12 days helps lower the levels of blood sugar and serum lipid peroxide, as
well as increase the concentration of serum insulin. Histologic observation has
shown that this injection could repair the structure of pancreatic inlet B cells
injured by alloxan.
PMID- 9642417
TI - [Protective effects of radix Salviae miltiorrhizae on azathioprine hepatotoxicity
in rats].
AB - The changes of liver function and malondialdehyde (MDA) and glutathione (GSH)
were studied in rats intoxicated with azathioprine (Aza) 15mg/(kg.d) and in rats
treated with Aza mixed Salviae 8g/(kg.d). The results showed that in the Aza
group, the levels of ALT, AKP, MDA increased and GSH decreased significantly in
week 1 and week 2. But in the Salviae group the levels of ALT, AKP, MDA decreased
and GSH increased significantly, approaching the normal levels, It follows that
Salviae has protective effects on Aza hepatotoxicity in rats.
PMID- 9642418
TI - [Anti-inflammatory and analgesic effects of scolopendra from different habitats].
AB - The water extracts of several species of the Chinese drug scolopendra from
different habitats can inhibit obviously the increased permeability of abdominal
blood capillaries and ear inflammation in mice. They can also raise the pain
thresholds in mice during hot-plate and writhing tests. Their toxicity is very
low.
PMID- 9642419
TI - Clinical psychology students' self-reported willingness to interact with persons
living with HIV.
AB - Previous research has indicated that health care workers, including those in
mental health, have negative attitudes toward people living with HIV and AIDS and
may be unwilling to work with them in a professional capacity. Ajzen's theory of
planned behavior (1985) was used as a model for better understanding the specific
components of these attitudes. In this project doctoral students in clinical
psychology read a vignette describing a person who is HIV positive and then
completed a set of measures regarding willingness to interact professionally,
level of knowledge and attitudes toward HIV and AIDS, and attitudes regarding
drug abusers and promiscuity. Results indicated that participants were generally
willing to provide therapy for an HIV positive client, although some participants
indicated that they would experience some anxiety in doing so. Level of anxiety
could be predicted by attitudes toward AIDS and whether the participants believed
that accepting an infected client would have negative effects for them personally
or professionally.
PMID- 9642420
TI - Evaluation of the effectiveness of AIDS health education interventions in the
Muslim community in Uganda.
AB - In 1992 the Islamic Medical Association of Uganda designed an AIDS prevention
project and conducted a baseline survey prior to community level activities.
Results of that baseline were previously reported in this journal. During 2 years
of prevention activities in local Muslim communities, 23 trainers educated over
3,000 religious leaders and their assistants, who in turn educated their
communities on AIDS during home visits and at religious gatherings. After 2
years, there was a significant increase in correct knowledge of HIV transmission,
methods of preventing HIV infection and the risk associated with ablution of the
dead and unsterile circumcision (p < 0.001). There was a significant reduction in
self-reported sexual partners among the young respondents less than 45 years. In
addition there was a significant increase in self-reported condom use among males
in urban areas (p < 0.001). Collaboration between health professionals and
religious leaders can be achieved and can contribute to the success of AIDS
prevention efforts.
PMID- 9642421
TI - Erotized, AIDS-HIV information on public-access television: a study of obscenity,
state censorship and cultural resistance.
AB - This study analyzes court records of a county-level obscenity trial in Austin,
Texas, and the appeal of the guilty verdict beginning with a Texas appellate
court up to the U.S. Supreme Court of two individuals who broadcast erotized AIDS
and HIV safer sex information on a public-access cable television. The trial and
appellate court decisions are reviewed in terms of argument themes, and the
nature of sexual value controversy is outlined. Erotic materials often conflict
with broad-based sexual and community values, and providing erotized HIV and AIDS
information products can be a form of radical political action designed to force
societal change. This study raises question as to how this trial and this type of
informational product might affect the programs and activities of information
resource centers, community-based organizations, libraries, and the overall
mission of public health education.
PMID- 9642422
TI - "Extramarital" sex: is there an increased risk for HIV transmission? A study of
male couples of mixed HIV status.
AB - This report describes the sexual behavior with "extramarital" partners of men who
are in committed relationships with men of opposite HIV status. We examined the
rates of unprotected anal sex with outside partners and compared these rates with
the prevalence of such activity within the couple, during the year prior to the
assessment. Seventy-five couples were interviewed, of whom 50 (67%) reported sex
outside of the primary relationship by one or both members of the couple. Rates
of unprotected anal sex with one-night stands and "other" partners were 25% and
33%, respectively among men who engaged in anal sex with such partners. In
contrast, 54% of the men who engaged in anal sex with their primary partner did
not always use condoms. Data from men who engaged in anal sex with both their
primary partner and one-night stand(s) revealed that condoms were used less
frequently within the primary relationship when the HIV negative men were the
insertive partner; otherwise the rates of unprotected anal sex were similar.
Approximately 75% of HIV negative men who engaged in receptive anal sex always
used condoms, and a similar proportion of HIV positive men always used condoms
during insertive anal sex, regardless of partner type. The vast majority of
unprotected anal sex occurred without ejaculation inside the rectum. Unprotected
oral sex was highly prevalent regardless of partner type. Implications for public
health policy and primary prevention research are discussed.
PMID- 9642423
TI - Gender differences in injection-related behaviors among injection drug users in
Baltimore, Maryland.
AB - Baseline data from 640 injection drug users in the Stop AIDS for Everyone study,
an HIV preventive intervention were used to examine gender differences in self
reports of injection behaviors. In both the bivariate and multivariate analyses
men reported injecting alone, in semipublic areas, and at their mother's
residence more often than women. In the bivariate analyses, women reported denser
personal networks, and in the multivariate analyses, women reported significantly
greater overlap between their drug and sex networks. These data suggest that this
overlap of sex and drug networks may reduce women drug injectors' ability to
adopt and maintain HIV protective behaviors. The data also suggest that
interventions need to address gender differences in the social context of risk
behaviors.
PMID- 9642424
TI - Gender and AIDS-related psychosocial processes: a study of perceived
susceptibility, social distance, and homophobia.
AB - Over the past decade, researchers have accumulated evidence that suggests six
main factors are associated with AIDS-related risk reduction behavior: (a)
perceived susceptibility (Dolcini et al., 1995; van der Plight & Richard, 1994);
(b) attitudes toward condoms (Catania et al., 1994; Maticka-Tynadale, 1991); (c)
personally knowing someone with HIV/AIDS (Joseph et al., 1987); (d) perceived
peer norms about risk-reduction (Maticka-Tyndale, 1991); (e) previous sexual
activity (Joseph et al., 1987); and (f) self-efficacy (Aspinwall, Kemeny, Taylor,
& Schneider, 1991; van der Plight & Richard, 1994). Furthermore, there is some
suggestion that the epidemiology and sociocultural constructions of the disease
has led to considerable gender, racial, and class differences in awareness of
AIDS, perception of HIV threat, and HIV-relevant behavior (Cohan & Atwood, 1994;
Dolcini et al., 1995; Gillies, 1994).
PMID- 9642425
TI - Homophobia, self-esteem, and risk for HIV among African American men who have sex
with men.
AB - Qualitative data from individual interviews with 18-29 year old African American
men, who have sex with men (n = 76) were used to examine the relationship of
negative attitudes toward homosexuality, self-esteem, and risk for HIV.
Respondents perceived members of their communities as holding negative attitudes
toward homosexuality, and many thought the African American community was less
accepting of homosexuality than the white community. There was evidence that
these negative attitudes are internalized by some of the young African American
men themselves. Respondents mentioned several ways that negative attitudes toward
homosexuality could lead to lower self-esteem and psychological distress in young
gay and bisexual men. In addition, respondents articulated several mechanisms by
which low self-esteem and psychological distress might be associated with sexual
behaviors that put one at risk for HIV. We concluded that addressing and changing
society's negative views of homosexuality are important components of a
comprehensive approach to reducing the transmission of HIV, especially among
young people in communities of color.
PMID- 9642426
TI - HIV prevention among Asian and Pacific Islander American men who have sex with
men: theories, research, applications, and policies. Introduction.
PMID- 9642427
TI - Epidemiology of HIV and AIDS among Asian and Pacific Islander Americans.
AB - As of June 1997 the Centers for Disease Control and Prevention reported 4,370
AIDS cases among Asian and Pacific Islander Americans (APIs) in the U.S. It also
reported that the rate of new AIDS cases among APIs men who have sex with men
(MSM) per 100,000 population increased by 55% from 1989 (4.0) to 1995 (6.2).
Focusing on the relatively low numbers of APIs with AIDS in the U.S. has resulted
in complacency among API communities and government officials, despite reports of
increased seroprevalence and exponential growth in diagnosed AIDS cases. However,
because of the geographic and social isolation of many Asian and Pacific Islander
American communities, the effect of HIV is magnified once it takes hold. The low
numbers of reported AIDS cases among API and the perception of them as the "model
minority" has reinforced their denial of AIDS as a threat. Data collection and
surveillance tools must be modified to accurately capture the range of HIV
related and social issues that affect Asian/Pacific Islander communities in the
United States. Notwithstanding sample limitations, ethnic-specific data are
needed to identify HIV trends in each of the Asian Pacific Islander American
communities, which can inform prevention and intervention programs.
PMID- 9642428
TI - HIV prevention among Asian and Pacific Islander American men who have sex with
men: a critical review of theoretical models and directions for future research.
AB - Nationally, the incidence of AIDS is increasing at a higher rate among Asian and
Pacific Islander American men who have sex with men (API MSM) than among white
MSM. Furthermore, current HIV prevention efforts are inadequate to slow the
rapidly rising HIV epidemic in the gay API community, and little attention has
been paid to the applicability of existing behavior change models to APIMSM. This
paper reviews the five major models of health behavior change used in HIV
prevention for the MSM population: the health belief model, theory of reasoned
action, social learning theory, diffusion theory, and the AIDS risk reduction
model. Although some of these models have been useful in designing risk reduction
programs for API MSM, recent empirical data suggest that the models do not
adequately address environmental influences affecting API MSM and limit our
choices in prevention strategies to the level of the individual. We propose an
ecological model for health promotion as a potentially useful theoretical
framework, and suggest prevention strategies directed at the individual, the
family, the general API community, and the mainstream gay community to reduce HIV
risk among API MSM.
PMID- 9642429
TI - HIV seroprevalence, risk behaviors, and cognitive factors among Asian and Pacific
Islander American men who have sex with men: a summary and critique of empirical
studies and methodological issues.
AB - The goals of this article are to (a) summarize and discuss published empirical
studies addressing HIV seroprevalence rates and HIV-related behaviors and
cognitive factors among Asian and Pacific Islander American (API) men who have
sex with men (MSM) in the United States, (b) examine existing population-based
research methodologies for studying HIV and AIDS prevention, (c) describe a
conceptual framework to facilitate the identification of ecologically sound or
culturally appropriate and competent methodologies for studying HIV prevention
among API MSM, and (d) discuss methodological issues and recommend alternative
methodologies to better understand this population in HIV prevention. A total of
eight published empirical studies reported the HIV seroprevalence rates, HIV-risk
behaviors, and attitudes toward HIV and AIDS among API MSM. Specifically, seven
studies reported HIV seroprevalence rates that were based on either self
disclosure of HIV status or HIV test results among the study participants. Four
studies also reported findings about the relationships between HIV-related
behaviors and cognitive factors. There are five population-based databases on HIV
and AIDS epidemiology and surveillance which have been managed by the Centers for
Disease Control and Prevention. Findings from the seven studies indicate that API
MSM are as likely to engage in HIV-risk behaviors as other groups. The present
analysis reveals that conventional surveillance or epidemiological techniques
(e.g., random digit telephone dialing), based on a singular model of populations,
are not appropriate to address culturally, linguistically and racially/ethnically
diverse groups of API MSM. To address the diversity of this group, ecologically
sound or culturally appropriate and competent research methodologies are needed.
Thus, a conceptual framework for such methodologies with examples was reviewed.
Two alternative methodologies, network analysis and venue-based sampling, were
briefly discussed.
PMID- 9642430
TI - Asian and Pacific Islander American HIV community-based organizations: a
nationwide survey.
AB - A national survey was conducted to (a) ascertain the status of HIV prevention
among community-based organizations targeting APIs in the United States, (b)
define technical assistance needs among these organizations, and (c) determine
their involvement in the HIV community planning process. Of the 80 surveys sent
out, 49 (61%) completed responses were received. Filipinos, Chinese, Vietnamese,
Cambodians, and multiracials were the subpopulations targeted the most often,
and, not surprising, Tagalog, Cantonese, Mandarin, Vietnamese, Cambodian, Korean
and Japanese were the Asian languages most widely in use. Gay men, bisexual men,
and youth were targeted most frequently by HIV prevention efforts. Of all the
largest ethnic subpopulations, Asian Indian is the only group with no community
based organization that exclusively targets them for HIV prevention. More than
95% of respondents reported conducting some type of evaluation; the size of the
budget and organization often determined the evaluation strategies used. Program
development, staff development, and program evaluation were the most frequently
reported areas of technical assistance requested. A majority of the respondents
(79%) reported being involved with the HIV prevention community planning process
where APIs were represented on state/local community planning groups, they did
not rate the performance of the community planning process highly. We recommend
providing technical assistance in fund-raising, program evaluation, and
participation in the HIV community planning process.
PMID- 9642431
TI - A profile of six community-based HIV prevention programs targeting Asian and
Pacific Islander Americans.
AB - Based on a framework (i.e., research and evaluation, prevention and services, and
advocacy and policy), the goal of this article is to profile six community-based
HIV prevention programs targeting Asian and Pacific Islander (API) Americans,
especially among men who have sex with men. These six programs were chosen based
on one or more of the following three criteria: (a) epidemiological profiles of
AIDS cases among Asian and Pacific Islander Americans, (b) ethnic diversity, and
(b) community development among Asian and Pacific Islander Americans in the fight
against HIV. The six programs are (a) the Kokua Kalih Valley Health Center,
Honolulu; (b) the Asian and Pacific Islander Wellness Center, San Francisco; (c)
the Asian Pacific AIDS Intervention Team, Los Angeles; (d) the Asian and Pacific
Islander Coalition on HIV and AIDS, New York City; (e) the AIDS Services in Asian
Communities, Philadelphia; and (f) the Massachusetts Asian AIDS Prevention
Project, Boston. The present analysis reveals that five programs have their roots
in the gay or bisexual communities. Two programs have existed for about 3 years
(the epidemic is going into its 17th year). Major financial support for the six
programs are federal, state, or county sources; private support is generally
minimal. All six programs offer a wide range of culturally competent and
linguistically appropriate prevention activities and services (including two
national projects) targeting a diverse API population. However, gaps in services
exist in the younger programs. In addition to a paucity of epidemiological,
surveillance, and empirical data, most reported that barriers fall into one or
two interrelated categories: (a) structural (e.g., lack of governmental or
private funding) or (b) cultural (e.g., denial of risk, homophobia, fear of
confidentiality). These findings suggest that HIV prevention activities and
services for Asian and Pacific Islander Americans should be based on empirical
and cultural data, and that API Americans should become more actively involved in
social and political activities. Asian and Pacific Islander American agencies are
challenged to integrate HIV with other health and social issues pertinent to the
communities.
PMID- 9642432
TI - Asians and Pacific Islanders and HIV prevention community planning.
AB - Since 1993, the Centers for Disease Control and Prevention (CDC) has required
state and local health departments to engage in a community planning process and
to develop HIV prevention plans to spend federal HIV prevention funds. This
analysis reviews the HIV prevention plans from 29 states, 5 local governments,
and 6 Pacific Island jurisdictions (61.5% percent response rate). The plans from
these 40 jurisdictions reflect the uneven implementation of HIV prevention
community planning efforts and the uneven progress is achieving CDC's core
objectives for HIV prevention community planning. Specifically, Asians and
Pacific Islanders (APIs) often are not represented in state and local HIV
prevention community planning groups. There also are significant gaps in the
manner in which HIV and AIDS surveillance data are collected and reported for
APIs. Finally, API populations are rarely included in HIV prevention priorities.
PMID- 9642433
TI - Will MCP-1 and RANTES take center stage in inflammatory diseases including
asthma?
PMID- 9642434
TI - Mediastinal fibrosis presenting as asthma.
AB - Asthma is one of the most common chronic medical conditions affecting children.
The usual presenting symptoms of asthma include wheezing, shortness of breath,
and dyspnea on exertion. Occasionally, children who present with one of these
respiratory complaints have a less common disorder. Mediastinal fibrosis is a
rare and incurable condition in which an excessive fibrotic reaction in the
mediastinum causes progressive cardiopulmonary compromise. The presentation is
variable: many patients present with respiratory symptoms such as cough,
wheezing, dyspnea, and/or hemoptysis, while others are asymptomatic and present
with a mediastinal mass discovered incidentally on a radiograph. With such a
broad array of presenting complaints, and a clinical course characterized by slow
progression of symptoms, the early stages of mediastinal fibrosis can mimic other
diseases such as asthma, chronic bronchitis, or the superior vena cava syndrome.
In this report we describe two patients with mediastinal fibrosis who were
initially thought to have asthma.
PMID- 9642435
TI - Postmortem serum levels of tryptase and total and specific IgE in fatal asthma.
AB - Sera were obtained postmortem from 55 subjects classified into three groups;
death due to asthma (FA, n = 21), asthmatic but death not due to asthma (NFA, n =
24) and a nonasthmatic control group (NAC, n = 10). A full autopsy was performed
on all cases and a medical history, including details of allergies, was obtained
by questionnaire from the next of kin. Grading of asthma severity by either
questionnaire or autopsy was comparable (tP = 0.435, p > 0.05) and the mean
pathology-grade was significantly higher for the FA group (3.375) compared to the
NFA group (2.375), p < 0.05. Tryptase was elevated (> 2.0 micrograms/L) in 21/55
sera (38%) and there was no significant difference between the groups. ROC plots
showed that tryptase levels did not discriminate between the FA and NFA groups,
even if specimens were collected within 24 hours after death. Total IgE was
significantly elevated in the FA group (geometric mean 140.3 kU/L) compared to
the other two groups (NFA 30.2 kU/L, NAC 9.4 kU/L), p = 0.05. Fatal asthmatics
also had a greater positivity (67%) to a screen for common inhalant allergens
than did the other groups (NFA 30%, NAC 20%). Sera with a positive screen were
tested against a panel of 10 common aero-allergens. Each sample was then assigned
a number (N) and a score (S), dependent on either the number of allergens
positive (N) or the total sum of pluses for all allergens (S). Both the N and S
values were higher for the FA group (N = 98, S = 264) than the NFA group (N = 52,
S = 151) and NAC group (N = 4, S = 8). The ratio (S/N) which gives an index (I)
was 2.69, 2.90, and 2.00, respectively. Tryptase was poorly correlated to the
total IgE level (r = 0.036); however, mean values for N and S were significantly
different (N 6.81, S 4.50, and N 19.25, S 11.5, p < 0.05) for sera with tryptase
levels < 2.0 or > or = 2.0 micrograms/L, respectively. We conclude that total and
specific IgE may be useful predictors of asthma severity but that postmortem
tryptase is not useful in the diagnosis of a fatal asthmatic attack.
PMID- 9642436
TI - Effectiveness and safety of fexofenadine, a new nonsedating H1-receptor
antagonist, in the treatment of fall allergies.
AB - Fexofenadine HCl is a new, nonsedating H1-receptor antagonist approved for
treatment of seasonal allergic rhinitis (SAR). In a double-blind, randomized,
placebo-controlled, multicenter trial, 588 patients with fall SAR rated the
severity of their symptoms using a scoring system at a screening visit and during
a 3-day placebo lead-in period. Patients who did not respond to placebo and met
symptom severity criteria were randomized to receive placebo or fexofenadine HCl
at 40, 60, or 120 mg bid at 7:00 a.m. and 7:00 p.m. for 14 days. Patients
continued to rate the severity of their symptoms immediately before receiving
each dose (at trough). A total of 545 patients were included in an intent-to
treat analysis. The change from baseline in the primary efficacy variable
(average daily 7:00 p.m. reflective symptom scores) was significantly greater in
patients receiving all dosages of fexofenadine HCl than placebo (p < 0.01). All
active dosages produced significant decreases (p < 0.05) in secondary end points:
7:00 a.m. reflective symptom scoring; 7:00 a.m. and 7:00 p.m. scoring 1-hour
before dose; and bedtime scoring 1-3 hours after the 7:00 p.m. dose. All dosages
of fexofenadine HCl were well tolerated, and no effect on QTc was observed. In
conclusion, fexofenadine HCl is safe and effective in the treatment of fall SAR,
with 60 mg bid being the optimal therapeutic dosage.
PMID- 9642437
TI - Asthma among the famous. Erwin Schrodinger (1887-1964), Austrian physicist.
PMID- 9642438
TI - Asthma among the famous. Padre Pio (1887-1968), Italian Roman Catholic Cleric.
PMID- 9642439
TI - Asthma among the famous. Edmund C. Blunden (1896-1974), British poet, biographer,
and literary critic.
PMID- 9642440
TI - Asthma among the famous. Howard Thurman (1900-1981), American minister, educator,
and author.
PMID- 9642441
TI - Static DNA cytometry as a diagnostic aid in effusion cytology: I. DNA aneuploidy
for identification and differentiation of primary and secondary tumors of the
serous membranes.
AB - OBJECTIVE: To determine whether DNA aneuploidy is a sensitive and specific marker
for the identification of tumor cells in effusions and whether the pattern of DNA
aneuploidy can provide important information for the differential diagnosis of
primary and secondary tumors of the serous membranes. STUDY DESIGN: One hundred
eight malignant mesotheliomas as well as 102 metastatic carcinomas of the serous
membranes were obtained from routine cytologic and histologic material. One
hundred reactive effusions were investigated as controls. Nuclear DNA contents
were measured after Feulgen staining using a TV image analysis system. RESULTS:
DNA aneuploidy was assumed if abnormal DNA stemlines, a coefficient of variation
of the first DNA stemline > or = 10%, or cells > 9c were observed. On this basis
the prevalence of DNA aneuploidy in mesotheliomas was 83% for cytologic and 84%
for histologic material. In effusions of metastatic carcinomas it was 100%. None
of the 100 reactive effusions revealed DNA aneuploidy (prevalence, 0%). Positive
predictive value for mesotheliomas was 100%; negative predictive value was 88%
for cytologic and 82% for histologic material. Positive predictive value for
metastatic carcinomas was 100%; negative predictive value was 100%. Seventy-two
percent of the mesotheliomas revealed their greatest stemline within the range
1.80c-2.20c, whereas none of the metastatic carcinomas showed this stemline
position. CONCLUSION: DNA image cytometry might be a very sensitive and highly
specific, additional tool for identification of neoplastic cells in effusions as
well as for the differential diagnosis of mesothelioma vs. metastatic carcinoma
of the serous membranes.
PMID- 9642442
TI - Static DNA cytometry as a diagnostic aid in effusion cytology: II. DNA aneuploidy
for identification of neoplastic cells in equivocal effusions.
AB - OBJECTIVE: The sensitivity of conventional cytology for identification of
neoplastic cells in effusions is unsatisfactory, about 58%. The rate of
diagnostically equivocal effusions in routine cytology is about 6%. DNA
aneuploidy has previously been proven to be a sensitive and specific marker for
the identification of tumor cells in effusions. In the present study we
determined if malignancy can be identified in cytologically equivocal cells in
effusions using DNA aneuploidy as a marker, thus decreasing the rate of
cytologically equivocal diagnoses in effusions. STUDY DESIGN: One hundred
cytologically equivocal effusions of the serous cavities were obtained from
routine diagnostic material. Nuclear DNA content was measured after Feulgen
staining using a TV image analysis system. Data were correlated with patient
follow-up. RESULTS: DNA aneuploidy was assumed if abnormal DNA stemlines, a
coefficient of variation of the first DNA stemline > or = 10% or cells > 9c were
observed. The sensitivity of DNA aneuploidy for the identification of malignancy
was 55.9%. Specificity of DNA nonaneuploidy for benignity was 94.1%. The positive
predictive value of the marker DNA aneuploidy for the occurrence of malignant
cells was 97.9% since all but one DNA aneuploid case showed malignancy in follow
up. CONCLUSION: Image cytometry applying DNA aneuploidy as a parameter is able to
detect the occurrence of malignant cells in cytologically equivocal effusions in
about every second case. Thus, this method is able to increase diagnostic
accuracy of conventional effusion cytology by decreasing the rate of
diagnostically equivocal effusions.
PMID- 9642443
TI - Characteristics of perisinusoidal collagenization in liver cirrhosis: computer
assisted quantitative analysis.
AB - OBJECTIVE: To determine the respective roles of septal fibrosis,
necroinflammatory activity, iron deposition, steatosis, and patterns of nodular
and septal remodeling in the collagenization of the perisinusoidal space in
livers from patients undergoing transplantation for alcoholic or posthepatitis C
cirrhosis and to ascertain whether perisinusoidal collagenization has clinical
implications added to those of septal fibrosis. STUDY DESIGN: Sixty-six
hepatectomy specimens from patients undergoing liver transplantation for
cirrhosis were analyzed. Thirty-two alcoholic and 34 posthepatitis C cirrhoses
were included. Picro Sirius-stained slides were examined with polarized light and
the amount of perisinusoidal collagenization measured by computerized image
analysis. Size distributions of septa and nodules were assessed by mathematical
morphology methods. RESULTS: The septal and perisinusoidal fibrosis indices and
Knodell and Pugh-Child scores showed significant differences between alcoholic
and posthepatitis cirrhoses. Correlation between septal fibrosis and
perisinusoidal collagenization was weak, though significant. Both variables
correlated significantly with the clinical score. The correlation was negative
between septal fibrosis or perisinusoidal collagenization and the Knodell score.
CONCLUSION: Perisinusoidal collagenization was not a feature of all cases of
cirrhosis, although it was more prominent in alcoholics. For the whole series, it
significantly correlated with the clinical score, which increased significantly
when high perisinusoidal collagenization was added to high septal fibrosis. No
absolute dependence was found between perisinusoidal collagenization and septal
fibrosis; percentage of slender fibrous septa and amount of iron deposition were
other factors entered in the regression equation.
PMID- 9642444
TI - Image cytometry of breast carcinomas that are DNA diploid by flow cytometry: time
to revise the concept of DNA diploidy?
AB - OBJECTIVE: To investigate whether breast carcinomas found to be DNA diploid by
flow cytometry (FCM) are still diploid if reassessed by image cytometry (ICM).
STUDY DESIGN: In a series of 286 breast cancers analyzed by FCM there were 100
(35%) cancers that were classified as DNA diploid. Fourteen of the 100 diploid
cases were selected for further analysis with ICM because the patient had died of
breast cancer within 11-84 months after the diagnosis (a group with unfavorable
outcomes), and 19 cases were selected at random from the cases who had no
recurrence of cancer during follow-up of six or more years (a favorable group).
RESULTS: Eleven (33%) of the 33 cases turned out to be DNA nondiploid, with a DNA
index > or = 1.2 when analyzed by ICM. Nine of the 11 DNA aneuploid samples by
ICM were found among the 14 patients with unfavorable prognoses and only 2 among
the 19 patients with favorable outcomes (P = .002). The five-year survival rate
of the women with DNA diploid cancer by both methods was 86%, whereas that of
patients with DNA aneuploid cancer by ICM was 36% (P = .002). CONCLUSION: The
results show that some breast carcinomas classified as DNA diploid based on FCM
are not DNA diploid by ICM and that such carcinomas are associated with poorer
outcomes than the ones that are DNA diploid also by ICM. The prognostic
significance of DNA ploidy in breast cancer may need to be reexamined in studies
where both FCM and ICM are used.
PMID- 9642445
TI - Diagnostic value of AgNOR staining in thyroid cytology.
AB - OBJECTIVE: To determine the value of the argyrophil nucleolar organizer region
(AgNOR) technique on scrape cytology of thyroid lesions. STUDY DESIGN: AgNOR
counts were evaluated in smears of 70 thyroid lesions that were sent for frozen
section and included 15 cases of follicular adenoma, 10 cases of follicular
carcinoma, 13 cases of papillary carcinoma, 23 cases of nodular goiter and 9
cases of Hashimoto's thyroiditis. Forty-one slides out of 70 were freshly
prepared, and 29 slides had been previously stained with hematoxylin and eosin
and then destained with alcohol. The number of AgNOR dots was recorded for 50
cells, and the mean number was calculated. RESULTS: The mean AgNOR counts were
statistically significantly higher in malignant lesions in comparison to benign
lesions. CONCLUSION: AgNOR staining could be of use in cytologic material from
thyroid lesions.
PMID- 9642446
TI - Role of planimetric analysis in diagnosing thyroid follicular lesions on fine
needle aspiration biopsies: a study with histologic correlation.
AB - BACKGROUND: Follicular lesions represent a gray area of interpretation in fine
needle aspiration biopsy (FNAB) of the thyroid, with as much as 25% inconclusive
reports. We identified "predominantly follicular lesions" (PFLs) as the cytologic
category most apt to take advantage of planimetric analysis to reach a more
definitive diagnosis. STUDY DESIGN: Sixty-eight cases of FNAB were diagnosed as
PFL among the 1,296 FNABs submitted to our institution between January 1994 and
June 1995. These cases underwent planimetric analysis with a Leica semiautomatic
image analyzer. A smear from a colloid nodule was used as a reference slide.
Nuclear areas, perimeters, form factors and maximum diameters were evaluated.
Cases in which nuclear areas and maximum nuclear diameters values were found to
be > or = 30% higher than the corresponding values found in the reference slide
were reported to the clinician as suspicious for malignancy ("flagged" by the
computer). These cases required closer follow-up with repeat FNAB within a month,
ultrasound and nuclear imaging studies. Nineteen of these cases underwent
surgical resection. RESULTS: Histologic reports diagnosed 9 cases of follicular
carcinomas, 4 cases of follicular adenomas and 6 cases of nodular hyperplasia.
When nuclear areas, perimeters and maximum diameters were all utilized, all the
malignant lesions were reported correctly by the computer analysis as flagged,
and all the benign lesions were reported as "not flagged." The sensitivity and
specificity were 100%, and statistically significant correlations were proven.
CONCLUSION: Although the above data provide strong evidence for the value of
planimetric analysis in differentiating between follicular lesions, we cannot
reach definitive conclusions on the basis of such a limited number of cases.
However, the results stimulated our current efforts in applying planimetry along
with the evaluation of other biologic markers to a larger set of cases.
PMID- 9642447
TI - Computer-assisted histometric analysis of tissue-engineered ovine bone.
AB - OBJECTIVE: To develop a computer-assisted histometric technique that
quantitatively determines the amount of regenerating bone, while excluding
fibrovascular tissue and void spaces, in tissue-engineered bone constructs. To
this end, a histometric technique was developed that couples digital tiling with
adaptive, multiband color thresholding (AMBCT). STUDY DESIGN: To test the
technique, a previously described model bone tissue-engineered construct filled
with morcellized bone graft was employed. Histometric techniques were applied to
quantify the amount of bone formed following eight weeks of implantation.
RESULTS: The histometric technique was able to yield quantitative information
regarding the amount of bone despite intrahistologic and interhistologic
differences in staining. The technique is user friendly and highly automated. In
addition to area fractions, the technique can provide bone ingrowth profiles as a
function of geometry and implantation time. CONCLUSION: Digital tiling coupled
with AMBCT offers an easy, fast and reproducible technique that aids in
quantification of bone within histologic sections. In addition, the technique can
be adapted to quantification of other tissues. Further studies are under way to
investigate the potential of correlating the histometric technique with
mechanical strength analyses of tissue-engineered bone specimens.
PMID- 9642448
TI - Prognostic value of stem cell line identification for renal cell carcinomas.
AB - OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy
level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight
variables were used to characterize DNA ploidy levels. They included DNA index
and seven others characterizing the presence of specific stem cell lines in each
of the 95 RCCs under study. All these variables were determined by means of
computer-assisted microscopy applied to Feulgen-stained nuclei. The actual
information contributed by each of the eight variables was determined by means of
univariate statistical analyses. RESULTS: The results showed that in the DNA
ploidy-related eight variables, the presence of at least 4% aneuploid nuclei with
> 5C DNA content was associated with the most significant prognostic value in
RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study
clearly showed that stem cell line characterization, and particularly the
presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs
with significant prognostic value. This kind of marker may help the
identification of patients who will develop metastases after surgery and for whom
adjuvant therapy might thus be indicated.
PMID- 9642449
TI - Prognostic significance of DNA ploidy and S-phase fraction in malignant serous
cystadenocarcinoma of the ovary.
AB - OBJECTIVE: To determine the prognostic value of DNA ploidy and S-phase fraction
in malignant serous cystadenocarcinoma of the ovary. STUDY DESIGN: Flow
cytometric analysis of nuclear DNA content was performed on paraffin-embedded
tissues of 31 serous cystadenocarcinomas of the ovary. DNA ploidy, DNA index and
S-phase fraction were determined without knowing the final outcome in the
patients. RESULTS: Histograms in 14 (46%) cases were aneuploid, whereas 17 (54%)
were diploid. Aneuploidy was more frequent at the advanced stages of the disease
as well as in the poorly differentiated histologic types. However, ploidy had a
prognostic influence: both the disease-free survival and overall survival were
better in diploid than aneuploid tumors at early and advanced stages. S-phase
fraction (SPF) could be correctly assessed in 19 cases (62%) and was > 15% in 21%
(4 cases). The survival of those patients, however, was not significantly
different from that of those with SPF < 15%. CONCLUSION: If used as an adjunct,
DNA ploidy is of value in predicting tumor behavior, response to chemotherapy and
disease recurrence.
PMID- 9642450
TI - DNA quantification as a prognostic factor in gastric adenocarcinoma.
AB - OBJECTIVE: To determine if DNA quantification, studied in cytologic samples
obtained by fiberendoscopy, has predictive value in gastric adenocarcinoma. The
survival times of patients in whom the tumor was the cause of death were
considered variables of interest. STUDY DESIGN: Twenty-nine patients with gastric
cancer, diagnosed by cytology, endoscopy and microbiopsy, were selected. The
study was done over more than 10 years. Smears were stained with progressive
hematoxylin and processed by computer for DNA evaluation by image cytometry.
RESULTS: Four different types of histograms that directly relate to tumoral
malignancy were obtained. These histograms were characterized by the value of
entropy. We established four grades of aggressiveness. Then we obtained two large
groups: high and low grade of malignancy. We studied the survival times in both
groups and constructed a Kaplan-Meier survival curve for the high grade of
malignancy group. We confirmed the results statistically and found that there was
a significant relationship, with P < .05. CONCLUSION: The use of DNA
quantification by image cytometry is strongly advised in daily surgery as a
prognostic indicator of survival time in gastric adenocarcinoma patients.
PMID- 9642451
TI - Sialadenosis of parotid gland: a cytomorphologic and morphometric study of four
cases.
AB - BACKGROUND: Sialadenosis is recurrent, noninflammatory, nonneoplastic enlargement
of salivary glands usually associated with an underlying systemic disorder.
CASES: Fine needle aspiration was performed on four patients with bilateral,
painless parotid swellings. The cytologic picture was distinctive and identical
in all the cases. Smears revealed clusters of swollen acini and numerous naked
nuclei of acinar origin in the background. There was absence of inflammatory
cells. Diagnosis of sialadenosis was made in each case. Morphometric measurements
were performed using an ocular micrometer. Results indicated a significant
increase in mean acinar diameter in a sialadenotic gland as compared to a normal
gland (76.03 microns vs. 53.79 microns). CONCLUSION: Cytomorphologic features of
sialadenosis are distinctive enough to enable its diagnosis on fine needle
aspiration. It is important to be aware of this entity as most cases do not
require surgical intervention.
PMID- 9642452
TI - Antisperm antibodies in men with psychogenic anejaculation.
AB - Antisperm autoantibodies were determined in 16 men suffering from psychogenic
anejaculation who underwent assisted reproduction treatments. Blood and semen
samples were collected after transrectal electroejaculation and antisperm
antibodies in serum and on the surface of motile spermatozoa were measured using
the direct and indirect immunobead binding test. Five men (31%) were found
positive for antisperm antibodies. The majority of antibodies were directed
against the sperm heads. Surface antibodies were mainly IgA isotype whereas serum
antibodies were IgG isotype. These results suggest that psychogenic anejaculation
might be associated with increased incidence of antisperm autoimmunity.
PMID- 9642453
TI - Birth after electroejaculation coupled to intracytoplasmic sperm injection in a
gun-shot spinal cord-injured man.
AB - We describe the case of a man who, after a gun-shot wound, has become paraplegic.
As a consequence of his spinal cord injury he developed infertility due to
incomplete erection and anejaculation. After several unsuccessful penile
vibratory stimulation attempts, it was possible to achieve ejaculation by means
of transrectal electrostimulation. However, the total sperm motility count, the
percentage of normal sperm morphology, and the vitality and hypo-osmotic swelling
test scores were rather low, and in particular viability was strikingly decreased
during sperm preparation. These parameters further decreased following
electroejaculate, forcing us to use intracytoplasmic sperm injection instead of
conventional in vitro fertilization for the treatment cycle. A normal pregnancy
was achieved which resulted in birth of a healthy girl on 1st January 1997.
PMID- 9642454
TI - Effects of cigarette smoking on semen characteristics of a population in Mexico.
AB - A study of semen quality was conducted in 197 smoking and 161 non-smoking men
undergoing initial infertility investigation. The men were allocated into groups
according the number of cigarettes smoked per day < 10 (n = 57), 11-20 (n = 115),
and > 20 cigarettes (n = 25). Smokers had significantly poorer sperm density (P <
.005), a lower percentage of viability (P < .007), a lower percentage of normal
sperm morphology (P < .005), and the percentage of motile sperm was lower (P <
.005). These parameters were worse in the heavy smoking groups. Thus the present
study corroborates reports of detrimental effects of cigarette smoking on sperm
characteristics. Further studies are needed to explain the mechanism by which
smoking affects spermatogenesis.
PMID- 9642455
TI - A neuropeptide in human semen: oxytocin.
AB - The neuropeptide oxytocin (OT) has been detected in testis and epididymis of
several mammals. The peptide affects steroidogenesis and sperm transport in vivo.
Effects of OT on sperm motility in vitro seems to be contradictory. As no data
are available on the presence of OT in human semen and on the relationship of OT
with sperm characteristics, we assessed OT level in semen samples in 3 groups of
patients: (I) normozoospermic, (II) astheno-/oligo-/teratozoospermic, and (III)
azoospermic subjects. Furthermore, we studied the relationship between the
concentration of OT in semen and the sperm characteristics. OT was measured in
seminal plasma by radioimmunoassay after extraction. OT semen levels did not
differ in control patients (I: 1.72 +/- 0.78 pg/mL; n = 10), patients with poor
semen quality (II: 1.66 +/- 0.91 pg/mL; n = 11), or in vasectomized patients
(III: 1.28 +/- 0.65 pg/mL; n = 11). No statistically significant relationships
between the OT levels and sperm characteristics (density: 0.0693; total sperm
count: 0.0845; percentage of motility: 0.1341; morphology: 0.3478) have been
found. The neurosecretory peptide oxytocin is present in human seminal plasma of
normal as well as of vasectomized subjects. OT is not only derived from the
testis; OT levels in poor semen samples are not different from controls. No
relationship was found between OT seminal plasma levels and sperm
characteristics.
PMID- 9642456
TI - Thyroid gland and epididymal sperm motility in rats.
AB - The purpose of this research was to investigate the effect of hypofunction of the
thyroid gland, caused by radioactive suppression of the gland, on the pattern of
spermatozoa motility in different segments of the rat epididymis. Thyroidectomy
was obtained by i.p. infection of 270 microCi of I-131. After about 30 days, the
animal reached hypothyroidism as determined by serum level of T4. When the
motility pattern of the sperm obtained from the epididymis of normal rats was
compared to that of hypothyroid animals, a drop in the parameter of path velocity
(VAP), progressive velocity (VSL), and track speed (VCL) were detected.
Hypofunction was associated with decreasing sperm motility in the epididymis. In
thyroidectomized rats injected with T4, no sperm motility changes were observed.
PMID- 9642457
TI - Declining sperm count and fertility in males: an epidemiological controversy.
AB - There have been several suggestions from different populations that sperm count
has decreased in the past 20 years. Concerns have, however, been raised in the
interpretation of these findings, particularly with regards to subject selection
mechanisms and data-analysis. Furthermore, these findings are inconsistent with
the reports that male infertility rates have remained constant during the past 3
decades. The increased number of men seeking consultation on infertility may only
be the result of the tendency of couples to delay pregnancy and the increased
availability of treatment. Moreover, sperm concentration is not always in itself
the determinant of male fertility, so the use of sperm count as an indicator of
male infertility in epidemiological studies should be considered with caution.
PMID- 9642458
TI - Unaltered protein pattern/genital tract secretion marker levels in seminal plasma
of highly viscous human ejaculates.
AB - SDS-PAGE (12.5%) analysis and neutral alpha-glucosidase, fructose, and zinc level
assessment were carried out in seminal plasma of 20 patients with highly viscous
ejaculates and of 20 control subjects, with the aim to investigate the relations
between high consistency of semen and epididymal, vesicular, and prostatic
secretions. Very low sperm motility was observed in all the patients' ejaculates,
both normo- and oligozoospermics. Protein patterns obtained in control and highly
viscous semina showed similar protein bands, in the range of 10-100 kD.
Furthermore, unaltered seminal neutral alpha-glucosidase, zinc, and fructose
level were measured in the same specimens. These results indicated no impairment
of epididymal, vesicular, and prostatic function in patients with hyperviscous
semina, while their normal electrophoretic seminal protein profile suggested
unaltered genital fluid interactions during the semen coagulation-liquefaction
process.
PMID- 9642459
TI - Loss of left testicular volume in men with clinical left varicocele: correlation
with grade of varicocele.
AB - It is reported that a clinical left varicocele is associated with loss of
ipsilateral testicular volume. We have examined the loss of left testicular
volume in infertile men with clinical left varicocele using ultrasound-derived
measurements of testicular volume. We have reviewed the testicular volumes,
maximum internal spermatic vein diameters, and the clinical reports of 404 men
presenting for infertility evaluation at our institution between 1992 and 1996.
Men with bilateral or subclinical varicoceles were excluded from the study.
Subclinical varicoceles were diagnosed by the ultrasonographic demonstration of
one or more veins having a maximal diameter of more than 3 mm. In men with
clinical left varicocele, mean left testicular volume was less than right
testicular volume (12.7 vs. 13.8 mL, P < .001). This finding was not observed in
men without varicocele (12.3 vs. 12.6 mL, P > .05). In men with left varicocele,
the difference between right and left testicular volume (right minus left)
increased with increasing varicocele grade. Our data demonstrate that a left
varicocele is associated with loss of left testicular volume. The results also
show that the degree of left testicular hypotrophy is proportional to the
clinical grade of the varicocele.
PMID- 9642460
TI - Interleukin-6 in seminal plasma of fertile and infertile men.
AB - Cytokines released by various cell subsets in the male urogenital tract are
capable of markedly influencing sperm function and fertility. Interleukin-6 (IL
6) levels were determined by "sandwich" enzyme immunoassay in the seminal plasma
of 77 men divided as follow: (1) into 7 groups according to the etiological
diagnosis of fertility, and (2) into 2 groups on the basis of normal or abnormal
spermiogram. There was a statistically significant association between IL-6 and
the patients' status (P < 0.0014). These results are due to statistically
significant differences between the groups with infection of the accessory
genital glands and normal controls, as well as between the groups with infection
of the accessory genital glands and that with varicocele, indicated by the
Honestly Significant Differences (HSD) test for multiple comparisons. There was
no significant difference of IL-6 levels between men with normal and those with
abnormal spermiograms. Furthermore, there was no correlation between IL-6 levels
and the variables of the spermiogram. The prostate seems to be the main site of
origin of IL-6 in the seminal plasma. Our data suggest that urogenital infections
may lead to elevated levels of IL-6 in the seminal plasma. This measurement of IL
6 in semen may provide clinically useful information for the diagnosis of male
accessory gland infection.
PMID- 9642461
TI - Testicular histology in experimental uremic rats.
AB - Testicular histology in chronic renal failure was studied using stepwise
nephrectomized and adenine-treated rats. Serum levels of urea nitrogen and
creatinine were significantly higher than those in sham-operated and control rats
(P < .001). However, the mean tubular diameter was not different among the 4
groups. Numbers of A-spermatogonia, preleptotene and pachytene spermatocytes, and
spermatids per 100 Sertoli cells were not different among the 4 groups. It would
appear that testicular histology is not influenced by chronic renal failure in
rats.
PMID- 9642462
TI - Germ cell apoptosis and endothelial nitric oxide synthase (eNOS) expression
following ischemia-reperfusion injury to testis.
AB - There is evidence to suggest that reactive oxygen species (ROS) are involved in
ischemia-reperfusion injury to the testis. Nitric oxide (NO), a ubiquitous free
radical produced by the nitric oxide synthases (NOS), has been implicated in
physiologic and pathologic interactions with ROS. We examined the effect of
testicular ischemia on germ cell apoptosis and endothelial NOS (eNOS) expression.
Adult rats were subjected to unilateral 720 degrees testicular torsion for 1 or 3
hours and 24 hours later, testes were harvested for immunohistochemical studies.
Apoptosis was detected by in situ 3' end-labeling of DNA with digoxigenin-ddUTP
and eNOS protein was detected using an eNOS monoclonal antibody. Tests subjected
to 3 hours of torsion had a threefold increase in apoptotic germ cells per cross
sectional area compared to sham testes (P < .05). In addition to its known
expression in Leydig, Sertoli, and vascular endothelial cells, eNOS was detected
in the cytoplasm of degenerating germ cells. Consecutive testis sections stained
for eNOS and cellular DNA fragmentation demonstrated co-localization of eNOS
protein and germ cell apoptosis. The detection of strong immunostaining in
apoptotic germ cells supports a role of eNOS in germ cell degeneration after
testicular ischemia-reperfusion and suggests that NO is associated with germ cell
apoptosis.
PMID- 9642463
TI - [Surveillance and prevention of animal rabies in the world].
AB - The author examines in turn methods and results for surveillance and control of
rabies in animals. Surveillance is essentially carried out by collecting
laboratory results from diagnoses of rabies in animals through direct
immunofluorescence in the sample or after mouse inoculation or inoculation in
cell cultures. Due to technical and financial constraints, the results collected
are usually insufficient in number, particularly in developing countries.
Surveillance of rabies is thus often based on data obtained from a non-target
species (human beings). Disease prophylaxis varies according to whether rabies is
found in wildlife or domestic animals. In both cases, there is at present a
tendency to abandon methods of sanitary prophylaxis by reducing the number of
vector-animals (fox, stray dogs, cats, bats, etc.), and instead to introduce
medical prophylaxis by preventive vaccination. As a result, oral vaccination has
already given spectacular results in the fight against rabies in foxes, and could
also be used for dogs. The author specifies the conditions for applying this
vaccination.
PMID- 9642464
TI - [Human African trypanosomiasis, contributions of experimental models].
AB - Melarsoprol has remained the chosen drug for the late-stage treatment of human
African trypanosomiasis (HAT) due both to Trypanosoma brucei (T.b.) gambiense and
T.b. rhodesiense; however, arsenical encephalopathies, which are often fatal,
occur in 5-10% of the treated cases. To date, two major problems have not been
solved. The first one is the precise diagnosis of early involvement of the
central nervous system (CNS) which determines the therapeutics to be
administered. The second one is linked to the lack of data on in vivo efficacy of
products which are effective in vitro against trypanosomes. Answers have to be
provided by experimental animal models of HAT. Such models would allow for better
studies of the pathology and pathogenesis of the disease, as well as therapeutic
trials of potentially effective new drugs or combinations. We have developed
acute and chronic murine and sheep experimental animal models of HAT infected by
T. b. brucei. Meningoencephalitis and neurological signs are relatively difficult
to obtain in murine models and require artificial means, such as suramin
treatment on day 21 after-infection. The chronic murine model has demonstrated
CNS involvement with meningitis, followed by meningoencephalitis with progressive
astrocytosis. The sheep model develops a disease with CNS complications and
cerebrospinal fluid can be collected. In the sheep model, we have described anti
galactocerebrosides antibodies, which represent major components of myelin, which
may indicate an autoimmune process in the CNS. We then described these antibodies
in the cerebrospinal fluids and sera from patients at a late-stage of the
disease. From a therapeutic point of view, we have cured mice or sheep with low
doses of melarsoprol, or with the nitroimidazole derivatives Ro 15-0216 and
megazol, alone or combined with suramin. Further studies of these nitroimidazole
compounds, which could be proposed for human use, have to be carried out on a
primate model infected by T.b. gambiense. To our knowledge, this primate model is
not available. This is why we have recently developed a T. b. gambiense primate
model of HAT on Cercopithecus aethiops.
PMID- 9642465
TI - [Fluctuations of serotonin and its metabolites in the lung and intestinal mucosa
in the rat infected with Nippostrongylus brasiliensis].
AB - The influence of parasitism on host biogenic amine levels was investigated in
Nippostrongylus brasiliensis infected rats. Amine levels were estimated in
tissues surrounding Nematods in their biological environment: the lung and
intestinal mucus. D0 being the day of infestation, tissues were obtained at 24,
30 and 45 hrs, and every day between D4 and D14 (when the rat was completely
deparasited by the self-cure phenomenon). Biogenic amines belonging to the
serotoninergic pathway were quantified by HPLC with electrochemical detection. In
the lungs and mucus, parasitism resulted in an important decrease in serotonine
(5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels, as opposed to the immediate
5-HT precursor, the 5-hydroxy-tryptophane (5-HTP). Host response to parasitism is
translated by serotoninergic pathway levels. This leads to two hypotheses: 5-HT
turn-over may be accelerated, but the inhibition of 5-HT synthetic enzyme, 5
hydroxytryptophane hydroxylase, by the parasite present in the host seems more
probable.
PMID- 9642466
TI - [Optimization of parasitological diagnosis of human intestinal microsporidiosis].
AB - The diagnosis of microsporidiosis by staining stools is known to be fast and
cheap. To obtain a specific and sensitive result, two colorimetric methods must
be used: staining by the fluorochrome Uvitex 2 B (VAN GOOL) and trichrome. Among
the four staining methods of trichrome currently studied, the WEBER coloration
could be considered as the most efficient. The density of microsporidia spores
could be semi-quantitatively evaluated, because their distribution is
homogeneous.
PMID- 9642467
TI - [Dynamics of Plasmodium falciparum gametocytemia as a function of therapeutic
response to chloroquine in a mesoendemic malaria zone].
AB - Patients with Plasmodium falciparum infections were selected with an in vivo
chloroquine sensitivity assay in a mesoendemic area of Senegal. Gametocytemia was
studied in relation to asexual parasite responses classified as drug-sensitive or
showing RI or RII resistance. Gametocyte prevalence and density appeared
significantly higher in resistant infections than in sensitive ones. These
observations were made on children as well as on adults. The period between first
clinical symptom appearance and treatment, varying from 0 to 5 days, was not
linked to asexual parasite responses, but was significantly and positively
correlated to gametocyte prevalence and density observed seven days after
beginning the treatment. The comparison between these results and those
previously observed in a hypoendemic area suggests that the dynamic of
gametocytemia is independent of the endemic level. These observations illustrate
that the dissemination of chimioresistant malaria can be reinforced--via the
gametocyte stage--by selective chloroquine pressure.
PMID- 9642468
TI - [Localized cutaneous leishmaniasis due to Leishmania infantum MON-1 contracted in
northern Algeria].
AB - Classically, the agent of the sporadic skin leishmaniasis in Northern Algeria is
Leishmania infantum MON-24. This paper reports the first documented observation
of localized cutaneous leishmaniasis due to Leishmania infantum zymodeme MON-1 in
Northern Algeria. The interest of using the Western blot serological analysis to
guide the diagnosis and the usefulness of the hamster inoculation to isolate
Leishmania from pauciparasitized lesion is demonstrated.
PMID- 9642469
TI - [Apropos of 1 case of hepatogastric fascioliasis in Cape Verde].
AB - The authors report a case of Fascioliasis sp. distomiasis with a double hepatic
and gastric location primitively associated with a gastric cancer metastazed to
the liver. The parasitic origin of the lesions suspected from the histological
specimen of the gastric biopsy (the presence of eggs) was confirmed by serology
with the presence of the arc 2 specific to immunoelectrophoretic analysis, while
the parasitological examination of the stools was always negative. The patient
grew well after a day's cure of triclabendazole (375 mg x 2). Although the
ectopic locations of Fascioliasis are classic, they are usually in the abdominal
wall, less frequently in the gastric or colic wall. The fact that the
contamination originated on the Cape Verde is indiscutable, since the patient had
never left the island. It is the 5th case described in medical literature, thus
confirming the presence of Fasciola hepatica (or gigantica) on the islands of the
Cape Verde, whose population is of both Portuguese and African origin and has
kept the eating habits of the former colonial power (Portugal is a zone of high
endemicity for human fascioliasis). It would be interesting to look for Limnaea
and contaminated bovine on the Cape Verde islands.
PMID- 9642470
TI - [Apropos of 1 Ivoirian case of osseus and cutaneous histoplasmosis by Histoplasma
capsulatum var. duboisii].
AB - Humeral, tibial and cutaneous localizations of Histoplasma capsulatum var.
duboisii were observed on a 6 year old boy. The diagnosis was made possible by
anatomo-pathological and mycological examinations. Treatment with terbinafine was
administrated for 4 months. The boy recovered without after-effects in the tibial
localization, but did suffer after-effects in the humeral localization.
PMID- 9642471
TI - [Primitive psoas abscess in children; diagnostic difficulties and non surgical
treatment: apropos of 2 cases].
AB - From an analysis of two files of children carriers of primitive psoas abscess,
the authors report the difficulties of diagnosis due to the rarity of this
affection and the similarities of its symptomatology with ostearthritis of the
hip which is a common pathology at the pediatric surgery unit of C.H.U. Yopougon
(Republic of Cote d'Ivoire). A non surgical treatment made of antibiotherapy and
traction fixed in the axis of the limb is proposed, since it helped the two
patients who had presented an echographical stage II of psoas abcess to recover
without after-effects.
PMID- 9642472
TI - [A case of asplenia in a sickle cell homozygote SS patient].
AB - One case of total splenic atrophy is reported in a patient with SS homozygous
sickle-cell disease presenting no related malformation, thus recalling the
IVEMARK syndrome. An abdominal echography and computed tomography are
indispensable in order to confirm the absence of the anatomic spleen; this makes
for a better follow-up of sickle-cell disease.
PMID- 9642473
TI - [Histoplasma capsulatum histoplasmosis: apropos of 1 case observed in the
internal medicine department of the CHU of Treichville (Abidjan)].
AB - The advent of AIDS has resulted in an increase in diseases which were previously
rare. In HIV-infected subjects, histoplasmosis takes a disseminated and
particularly severe form, with a fatal outcome in our country, the more so
because the clinical presentation resembles tuberculosis and is generally treated
as such. The authors report a case of disseminated histoplasmosis in a patient
dually-reactive to HIV-1 and HIV-2, in whom the clinical presentation was fever,
mediastinal lymphadenopathy and pulmonary infiltrates. The diagnosis of
histoplasmosis was made at autopsy.
PMID- 9642474
TI - [Cutaneous lesions, viral risk and marine bird ticks, a world wide problem;
apropos of 1 case with pseudo-zoster lesions].
AB - Dermatological injuries provoked by tick bites deserve more attention. The
authors present the clinical observation of a young woman bitten in Brittany by
the marine bird associated tick Ornithodoros (A.) maritimus and presenting pseudo
zoster skin lesions. Two other individuals working together with the patient and
also bitten by this tick showed symptoms of prurigo, fever and vomiting. Marine
bird associated ticks bites may also be responsible for the inoculation of a
number of arboviruses along all the coasts of the world including those of
islands of Indian Ocean. Pathogenesis of the skin lesions is discussed according
to the authors' histo-pathological findings.
PMID- 9642475
TI - [No variation in chloroquine resistance (Plasmodium falciparum) from 1986 to 1996
in semi-immune children in Brazzaville (Congo)].
AB - A simplified Plasmodium falciparum in vivo test was carried out in Brazzaville
(Congo) in April 1996. Chloroquine was prescribed at 25 mg/kg for 3 days in
asymptomatic Brazzavillian school children who presented parasitemia > 800 P.
falciparum trophozoites and lived in a highly endemic district. A massive
decrease of parasitemia was observed on day 2. The percentage of resistance
(presence of P. falciparum trophozoite on day 7 in a thick blood film) was 43.5,
28 and 21 respectively (IC: 95%: 29-57, 15-41 & 10-34) at the threshold of 6, 50
and 100 parasites/microliter. In positive children on day 7 the reduction of
parasitemia was > 95% and no case of R3 resistance was detected. A comparison
with previous studies carried out in 1985, 1986, 1990 and 1993 in the same school
using the same methodology proves the long-lasting stabilization of chloroquino
resistance for this semi-immune indigenous population.
PMID- 9642476
TI - [Potability of drinking water sold in bags to public primary school children in
Abidjan].
AB - This study was carried out in order to determine the potability of drinking water
sold in bags near 26 primary schools in Abidjan. Samples of this water revealed
its poor microbiological and chemical quality. This exposes consumers to health
risks. Consumers should be informed of the danger involved while vendors should
be educated and their activities monitored by the Municipal Health services.
PMID- 9642477
TI - [Intestinal parasites in the vendors and consumers of street food. A study
conducted in the Dakar area].
AB - In order to assess the parasitic risk for street-food consumers, the authors
conducted two studies from September to August 1996, one on street-food sellers
(305) and the other on consumers (235). Among the consumers, 127 were considered
as not exposed to risk, since they did not frequent the sector being surveyed,
and 108 were exposed because they consumed at least one meal per day cooked by
the sellers of this area. Both groups filled out a questionnaire and had their
stools analysed according to the RITCHIE method. The infection rate was 60% among
sellers and 45.5% among consumers. Protozoans were predominant in both groups.
Among the consumers, those exposed were significantly more infected. Even though
the sellers represent a parasitic risk due to their level of infection and the
typology of parasites they shelter, one cannot assume that consumers are
contaminated only by the sellers of street food. However, appropriate measures
must be implemented in order to minimize risks for street-food consumers.
PMID- 9642478
TI - [Occurrence of onchocerciasis in subjects coming from non-endemic areas and
migrating to a hyperendemic area].
AB - The incidence of Onchocerca volvulus infection was measured from 1992-93 to 1995
in six villages of initially uninfected migrants who settled in 1991 in the Vina
Valley (Cameroon), an area of ongoing transmission of onchocerciasis. The mean
annual incidence (MAI) exceeded 20% in the three communities located in the first
line, and fewer than 15 km from the hyperendemic areas of the Central African
Republic. The MAI was lower than 16% in the second line communities. As these
populations are particularly at risk of developing ocular complications from
onchocerciasis, it is recommended that repeated ivermectin distributions be
organized in the migrant villages of the Vina Valley.
PMID- 9642479
TI - [Is onchocerciasis endemic to Nyanza Lac (Burundi)?].
AB - Several cases of onchocerciasis have been detected among suspected patients at
the Nyanza Lac health centre, in southern Burundi. Surveys in three 'collines'
(administrative units) of the commune of Nyanza Lac confirmed the presence of the
disease (5.5% in the sample). However, all the onchocerciasis patients were
adults and had immigrated from the near-by province of Bururi, where
onchocerciasis is endemic. Furthermore, no aquatic forms of simuliid flies have
been found in the prospected watercourses and the environment is not
characteristic of an endemic region. Thus, one can conclude that onchocerciasis
is imported, and not endemic, in the commune of Nyanza Lac, but that the
proximity of other endemic areas could entail a risk of transmission.
PMID- 9642480
TI - [Detection of hepatitis C virus in the general population of Tunisia].
AB - We searched for antibodies to hepatitis C in a sample of 3079 Tunisians in the
suburban area of Tunis. 30 people were positive by ELISA and 22 were confirmed by
immunoblotting. This result represents a prevalence of 0.71% which is close to
the values reported in European countries of the Mediterranean area.
PMID- 9642481
TI - [Entomologic study on the transmission of onchocerciasis in a forest-savanna
transition area of Cameroon].
AB - An entomological study was conducted in the basin area of middle Sanaga
(Cameroon) in order to document the pattern of onchocerciasis transmission in a
region where a high prevalence of infection had been recorded in villages located
30 km from the main rivers. The main vector of O. volvulus was found to be S.
squamosum s.s. No breeding site was found in the small tributaries of the Sanaga
and Mbam Rivers, and the dispersal of S. damnosum s.l. in the area thus appeared
to be particularly high. The highest blackfly population densities were recorded
during the long rainy season, and a second peak of density occurred along the
Mbam River during the short rainy season. A seasonal variation in dispersal
patterns was found at three of the four transects studied. The transmission of
Onchocerca volvulus in the area occurred principally between January and May
(i.e. at the end of the long dry season and the beginning of the short rainy
season). Vector control operations might well reinforce the effect of ivermectin
distributions in this onchocerciasis focus.
PMID- 9642482
TI - [Anthropologic research and understanding pediatric visceral leishmaniasis in
Tunisia].
AB - In order to determine the social and cultural factors which delay hospitalization
of children suffering from visceral leishmaniasis (VL), a study was carried out
in the rural area of Kairouan (Tunisia). Qualitative techniques were used to
investigate beliefs and behaviours associated with the symptoms of VL. The study
has demonstrated that the folk interpretation of the disease interferes largely
with the choice of the therapy. Regarding VL, the subdivision of the disease into
two groups of symptoms, fever and splenomegaly, incites parents to consult
doctors in the presence of fever and use traditional healers when splenomegaly
appears. This is responsible for long delays before the patients can have access
to official health care. This investigation clearly demonstrated that a health
education programme is needed in VL endemic areas in Tunisia in order to shorten
delays between the appearance of symptoms and their diagnosis. For this objective
to be achieved, it would also seem necessary to implement simple serodiagnostic
techniques at the periphery level.
PMID- 9642483
TI - Optimum treatment of stable angina pectoris.
AB - From a therapeutic point of view, angina pectoris is best thought of as an
imbalance between oxygen supply and demand. Oxygen supply to the heart can be
increased by improving endothelial function to increase vasodilation. Non
endothelial-mediated vasodilation will also help increase coronary flow. Coronary
vasodilators, such as the calcium blockers and nitrates, are effective agents in
relieving vasoconstriction and improving coronary blood flow. Reduction of oxygen
demand is accomplished by decreasing heart rate, blood pressure, heart size, and
left ventricular mass. Beta-blockers and heart rate-lowering calcium entry
blockers are effective in reducing oxygen demand. Additive effects occur by
combining a beta-blocker and a dihydropyridine calcium entry blocker. Together
with reduction of risk factors, this combination therapy plus aspirin provides
optimal management of patients with angina pectoris.
PMID- 9642484
TI - Proposed synergistic effect of calcium channel blockers with lipid-lowering
therapy in retarding progression of coronary atherosclerosis.
AB - Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic
modality to retard the progression of coronary atherosclerosis. An additional
approach for prevention of the progression of atherosclerosis is calcium channel
blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is
less unequivocal than the clear evidence for lipid-lowering therapy. Many
investigations support the view that a number of key processes in atherosclerosis
may be influenced by CCBs. From the "negative" and "positive" studies with CCBs
performed in animals and humans we must conclude that apparently some, but not
all, types or stages of the atherosclerotic process are inhibited by CCBs. To
assess whether lipid-lowering therapy and CCB treatment may have an additive or
synergistic beneficial effect on human atherosclerosis, which is conceivable
because their anti-atherosclerotic properties differ, data from the angiographic
lipid-lowering trial REGRESS (pravastatin vs. placebo) were reviewed. In REGRESS,
patients in the pravastatin group had significantly less progression if cotreated
with CCBs as compared with those with no CCB cotreatment, whereas in the placebo
(no pravastatin) group no effect of CCB treatment was observed. With respect to
angiographic new lesion formation, in the pravastatin group there were 50% less
patients with new angiographic lesions if cotreated with CCBs as compared with no
CCB cotreatment, whereas in the placebo (no pravastatin) group, again, no
significant effect of CCB treatment was observed. No beneficial effects of CCB
treatment on clinical events were observed during the 2-year study follow-up. In
view of the correlation between angiographic progression and subsequent clinical
events as demonstrated in several large trials, it is not unrealistic to also
anticipate in this population, a beneficial effect on clinical events with longer
follow-up. Although the REGRESS trial was not designed to evaluate combination
therapy, the results suggest that addition of CCBs to HMG-CoA reductase inhibitor
therapy (pravastatin) acts synergistically in retarding the progression of
established coronary atherosclerosis. These results appear to warrant prospective
randomized trials to determine in a more definitive manner the merits of this
combination in the prevention of progression of coronary atherosclerosis.
Currently a number of studies in these fields are being designed or are already
underway.
PMID- 9642485
TI - Treatment of angina pectoris with calcium antagonists: long-term follow-up.
AB - This study was designed to investigate the association of calcium channel blocker
(CCB) use with subsequent mortality in a group of patients with chronic stable
angina. CCBs have been proven effective in the treatment of angina pectoris.
Recently, the safety of CCBs in hypertensive and coronary artery disease patients
has been challenged. New prospective controlled studies with nifedipine are under
way that may help define the long-term safety of CCBs in the treatment of these
patients. Until these studies are concluded, long-term data on mortality among
CCB users may be informative. From 1990 to 1992, 11,575 patients with coronary
heart disease were screened but not included in a secondary prevention study with
bezafibrate conducted in 18 cardiac departments in Israel. Of these patients,
2390 had chronic angina without a history of myocardial infarction and were
followed for subsequent mortality over 4-6 years (mean 5.2 years). From this
patient population, 1366 (57%) reported receiving a CCB. They included more women
and hypertensives, and a greater proportion of them exhibited a higher severity
of anginal class than counterparts not treated with a CCB (n = 1024). The
mortality in patients treated with CCBs was similar to those not treated with
CCBs (11.5% vs. 11.6%; P = 0.53). A multivariate analysis accounting for
differences in age, sex, and other clinical parameters associated with increased
risk evaluated the estimated hazard ratio (HR) of death of patients treated with
CCBs compared with those not treated with CCBs (HR = 0.89; 95% CI = 0.68-1.16).
In Cox regression analysis, the adjusted HR of death of patients treated with
nifedipine or diltiazem, together with a beta-blocker, was 0.85 (95% CI = 0.47
1.54) and 0.47 (95% CI = 0.24-0.90), respectively. After a follow-up of 4-6 years
(mean 5.2) there was no evidence of increased mortality risk associated with CCB
use among coronary heart disease patients with chronic stable angina. However,
due to wide confidence intervals and possible confounding factors, randomized
control studies are required to provide definitive information.
PMID- 9642486
TI - Endothelial function: strategies for early intervention.
AB - Assessment of endothelial function appears to be a valuable additional tool for
diagnosing and therapeutic monitoring of coronary artery disease. The first part
of this review discusses the biosynthesis, degradation, and antiatherosclerotic
properties of nitric oxide, a major determinant of endothelial function. In the
second part methods for assessing endothelial function and strategies for
reversal of endothelial dysfunction are reviewed. Improvement of endothelial
function may be obtained by lifestyle modifications, such as cessation of
smoking, better blood glucose regulation, exercise, dietary measures, and
pharmacological interventions, such as lipid lowering, antioxidant therapy,
angiotensin-converting enzyme inhibition, and calcium channel blockers.
PMID- 9642487
TI - Effect of lipid-lowering therapy on myocardial ischemia.
AB - Myocardial blood flow in patients with coronary artery disease depends on the
severity of the coronary narrowings and the functional status of the coronary
vessels. Coronary atherosclerotic plaques, which contain high concentrations of
lipids, are more sensitive to change in coronary tone. The increased tendency of
these active plaques for vasoconstriction is caused by abnormal endothelial
function. Because regression of significant coronary plaques is highly unlikely,
effort is made to improve endothelial function, thereby improving myocardial
blood flow. Reduction of the cholesterol level by lipid-lowering drugs is
associated with restoration of the vasodilatory response of the coronary
arteries, thereby reducing the likelihood of plaque rupture and its consequences:
myocardial infarction and death. Myocardial ischemia during daily life is induced
by increased demand and increased coronary tone; therefore, it was not surprising
that recent studies have indicated that cholesterol lowering reduced the
frequency of daily ischemic episodes. Because improvement in endothelial function
is already observed within a few weeks/months of lipid lowering, it is hoped that
this therapy will rapidly reduce the frequency and severity of myocardial
ischemia and its clinical expression, angina pectoris. At a later phase (1-2
years), cholesterol lowering will also reduce major cardiac events.
PMID- 9642488
TI - Cerebral dura mater and cephalalgia.
PMID- 9642489
TI - Return to the headache in systemic lupus erythematosus using modern technology.
PMID- 9642490
TI - Is cluster headache due to indolent inflammation in the cavernous sinus?
PMID- 9642491
TI - Dopamine and migraine: a review of pharmacological, biochemical,
neurophysiological, and therapeutic data.
AB - The dopamine theory of migraine pathogenesis, first proposed by F. Sicuteri in
1977, has attracted renewed interest after an increased frequency of the dopamine
D2 receptor (DRD2) gene allele NcoI C was found in patients with migraine with
aura. Therefore we reviewed the relevant literature. The most compelling argument
favoring an interictal hypersensitivity of dopamine receptors in migraineurs
stems from pharmacologic studies of the gastric and autonomic effects of
dopaminergic agents such as apomorphine, but none of these studies was blinded
and placebo-controlled. Various DRD2 antagonists abort migraine attacks after
parenteral administration, while there is circumstantial evidence that dopamine
agonists may be useful for prophylaxis. Most drugs used in these trials, however,
lack selectivity for dopamine receptors. Both in pharmacological and therapeutic
studies most patients had migraine without aura. We conclude that data suggesting
a primary role for the dopaminergic system in migraine pathogenesis are
unconvincing. Based on well established interactions between central amines, a
reduced release of serotonin between attacks could lower dopamine release which
would lead to receptor hypersensitivity.
PMID- 9642492
TI - Cerebral dura mater and cephalalgia: relationships between mast cells and
catecholaminergic nerve fibers in the rat.
AB - The aim of the present study was to examine whether mast cells have the same
variations as the related catecholaminergic nerve fibers. Chemical sympathectomy
or surgical removal of right superior cervical ganglion induced a rapid decrease
of fluorescence in both nerve fibers and mast cells, as confirmed by quantitative
analysis (nerve fibers 19 +/- 1.1 vs 1.3 +/- 0.6; mast cell 10.8 +/- 1.9 vs 2.1
+/- 0.3). The results of quantitative analysis after nerve fiber stimulation
(electrical), however, showed an increase of the fluorescence in both the nerve
fibers and the mast cells (nerve fibers 43.4 +/- 2.4; mast cells 18.6 +/- 1.6).
Moreover, we found that the basal zone is more innervated (regarding
catecholaminergic nerve fibers) than the apical one, and that the fluorescence
level decreases passing from the vasal zone to the perivasal and intervasal
zones. Further studies are needed in order to clarify the role of fluorescent
nerve fibers and mast cells of cerebral dura mater in cephalalgia.
PMID- 9642494
TI - Flow cytometric analysis of lymphocyte subsets in migraine patients during and
outside of an acute headache attack.
AB - We have conducted flow cytometric studies of two subsets of lymphocyte markers in
groups of migraineurs during (n = 12; group B) and outside (n = 10; group C) of a
migraine without aura attack (total n = 22; group A), including a group of
patients tested in both of these phases (n = 5; group D), and compared these
results with those obtained from a population of age-comparable, sex- and race
matched healthy volunteers (n = 12; group E). Comparison of the first set of
lymphocytes (CD3+CD16 + 56+, CD3-CD16 + 56+, CD3-CD19+, CD3+CD19+, and CD3+HLA -
DR+) between the patients in group A and the controls (group E) showed
differences, reflecting greater group A percentages of CD3+CD16 + CD56+ and CD3
CD19+ lymphocytes. Furthermore, these differences reached statistical
significance only for the CD3+CD16 + CD56+ lymphocytes, and then solely for the
patients in group C (Scheffe's test, p < 0.05). Paired analysis of the above
lymphocyte markers for subjects in group D failed to show significant differences
between patients when they were having and not having a migraine attack, raising
the possibility that results from a larger study could show meaningful increases
in percentages of CD3+CD16 + CD56+ lymphocytes as one of the immune parameters
useful for differentiating migraineurs from controls. Comparison of a second set
of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among
either the different groups of patients or between the patients and controls
failed, however, to show statistically significant differences, emphasizing the
apparent specificity of the findings described above for CD3+CD16 + CD56+
lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence
of significant, differential changes in lymphocyte subset immunophenotyping
between groups of pain-free migraineurs and patients during an acute migraine
episode or controls. Corroboration of these findings may prove useful in clinical
laboratory practice to identify changes in immunological parameters specifically
associated with migraineurs, and help towards a better understanding of the
etiology and pathophysiology of this condition.
PMID- 9642493
TI - A study of adaptive responses in cell signaling in migraine and cluster headache:
correlations between headache type and changes in gene expression.
AB - The project was an investigation into whether changes in the expression of G
proteins underlie altered cell signaling in migraine and cluster headache. The
basis for this assumption is that altered physiological responses are seen in
migraineurs and that differences in cell signaling are detected biochemically in
various cell types isolated from peripheral blood. Levels of three G-protein
mRNAs--Gs alpha, Gi alpha, and Gq alpha, were quantified in lymphocytes from
clinically well-defined migraine and cluster headache patients and correlated
with headache type and influence of drug treatment. Gi alpha mRNA was reduced by
50% in all migraine patients compared with control subjects; similarly in
patients with or without aura, in patients with a migraine headache at the time
of sampling, and patients in a quiescent state. No reduction in the levels of Gs
alpha of Gq alpha mRNA were seen in migraine patients. A smaller reduction was
seen in cluster headache patients, most marked in those without medication.
Levels of Gs alpha mRNA were significantly reduced in cluster headache patients
compared with migraine patients. The marked down-regulation of Gi alpha mRNA in
migraine, whether quiescent or acute, indicates either an adaptive response to
headache in this group of patients or that low levels of Gi alpha mRNA make
individuals more susceptible to migraine.
PMID- 9642495
TI - Age-related cerebrovascular disease alters the symptomatic course of migraine.
AB - Migraine headaches usually decrease in frequency and severity and often cease
during advancing age. Occasionally, migraineurs report late-life migrainous
accompaniments, i.e., auras without headache, particularly when typical migraine
attacks terminate or diminish following major or minor strokes, at which time the
auras may become atypical. Clinical observations such as these suggest that
degenerative cerebrovascular changes accompanying aging may modify the course of
migraine headaches particularly those with aura. To test this hypothesis, we
quantitated age-related changes in cerebral vasodilator capacitance by measuring
local cerebral blood flow utilizing xenon contrast computed tomography (CT)
scanning before and after oral administration of the pharmacological cerebral
vasodilator, acetazolamide (Diamox). Measurements were compared among 27 normal
volunteers without headache (aged 24-94 years; mean age 61.1 +/- 17.6) and 37
carefully categorized groups of migraine patients (aged 27-83 years; mean age
59.4 +/- 12.4). The normals comprised Group A. Migraineurs were divided into two
subgroups: Group B consisted of 27 migraineurs with and without aura who
continued to suffer from incapacitating and frequent headaches and Group C
consisted of 10 migraineurs who no longer suffered from severe and frequent
headaches, two of whom still complained of atypical auras of the "late-life
migrainous accompaniments" type. Cerebral vasodilator capacitance significantly
declined with advancing age among normals and the two groups of migraineurs,
confirming the development of age-related cerebrovascular diseases. Global CBF
increases after Diamox in Group B (with persistent and severe migraine), were
significantly greater compared with normals without headache, and with Group C
consisting of migraineurs whose headaches had decreased, subsided, or become
replaced by late-life migrainous accompaniments (Group C). Results establish that
cerebrovasodilator capacitance declines with advancing age, probably due to
progressive cerebral atherosclerosis, since these declines were accentuated by
risk factors for stroke, particularly TIAs or documented lacunar infarcts by CT.
Progressive impairments of cerebral vasodilator capacitance among migraineurs
were associated with: (i) reductions in frequency and severity of migrainous
cephalalgia and (ii) appearance of late-life migrainous accompaniments.
PMID- 9642496
TI - Structural and neurochemical markers of brain injury in the migraine diathesis of
systemic lupus erythematosus.
AB - OBJECTIVE: To determine whether migraine in systemic lupus erythematosus (SLE) is
associated with accentuated brain injury and disease activity. METHODS: Forty SLE
patients (11 without headache, 11 with non-migraine headache, and 18 with
migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and
spectroscopy (MRS). RESULTS: Recurrent headache occurred in 75% of SLE patients.
MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in
SLE was not associated with increased disease activity or severity,
neuropsychiatric manifestations, or end-organ involvement compared to patients
without migraine (p > 0.05). There were no differences in the prevalence or
severity of MRI or MRS abnormalities between SLE patients with migraine, with non
migraine headache, or without headache (p > 0.05). CONCLUSIONS: Headache does not
identify SLE patients at risk for brain injury, increased disease activity, or
increased end-organ involvement. Aggressive immunosuppressive therapy for
headache alone is not indicated in SLE.
PMID- 9642497
TI - Peripheral autonomic potentials in primary headache and drug-induced headache.
AB - Autonomic functions of different primary headache types have been investigated in
several studies, most of them analyzing cardiovascular reflex mechanisms or
biochemical changes. The results are contradictory; only in tension-type headache
and in cluster headache has a sympathetic hypofunction been shown in a
preponderance of studies. We analyzed the peripheral autonomous potentials (PAPs)
in different primary headache types and in drug-induced headache and compared the
results with those of healthy subjects and of patients with low back pain.
Latencies of PAPs were significantly increased in all headache types but not in
low back pain; amplitudes of PAPs did not show significant differences compared
to healthy subjects. Patients with a long duration of drug abuse had increased
PAP latencies, whereas patients with a high number of migraine attacks per year
had decreased latencies. Our data suggest that sympathetic hypofunction as
measured by PAP latencies is a general phenomenon in headache but not in all pain
syndromes. Drug abuse leads to an increase of this hypofunction. While measuring
PAPs is not an appropriate method by which to differentiate between headache
disorders, it allows assessment of autonomic disturbances in primary and drug
induced headache.
PMID- 9642498
TI - Orbital pain as an isolated sign of internal carotid artery dissection. A
diagnostic pitfall.
AB - Head pain is one of the main presenting symptoms of internal carotid artery (ICA)
dissection, usually in association with ischemic and/or local signs such as
Horner's syndrome, lower cranial nerve palsies, or tinnitus. In rare cases, head
pain remains isolated and mimics other conditions. We report a patient who
suffered isolated prolonged orbital pain as the only sign of intrapetrous ICA
dissection. Early recognition of such unusual facial pain may be crucial in
decreasing the risk of secondary cerebral or retinal ischemia.
PMID- 9642499
TI - Hypnic headache syndrome: a case with good response to indomethacin.
AB - Hypnic headache syndrome is a rare benign disorder which occurs in the elderly.
It presents as a holocephalic or, less frequently, hemicranial headache during
night sleep, lasting between 20 and 180 min; it is not associated with autonomic
signs and responds well to lithium carbonate. We report a new case which
responded well to indomethacin, and suggest that indomethacin may be used as an
alternative treatment in this rare headache syndrome of the elderly.
PMID- 9642500
TI - Please don't hi-jack "quality of life".
PMID- 9642501
TI - Hormone-related headaches.
PMID- 9642502
TI - The transition G to A at position 20210 in the 3'-untranslated region of the
prothrombin gene is not associated with migrainous infarction.
PMID- 9642503
TI - Human cytomegalovirus: a viral complication in transplantation.
PMID- 9642504
TI - Renal transplantation in secondary systemic amyloidosis.
AB - When renal amyloidosis has progressed to end-stage renal failure, most patients
are severely affected by systemic amyloidosis and nephropathy. An alternative to
chronic dialysis is renal transplantation. We present a patient with amyloid
nephropathy who developed recurrent transplant amyloidosis. Renal transplantation
was performed in 1985 with a living related donor. In 1990 the patient developed
amyloidosis of the graft with membranous nephropathy and tubular acidosis due to
hyporeninemic hypoaldosteronism. Secondary amyloidosis has been reported to
involve glandular organs inducing hypothyroidism, hypocortisolism and
hypoaldosteronism. Cyclosporine has been reported to induce hyporeninemic
hypoaldosteronism and tubular acidosis, but not hypocortisolism and
hypothyroidism. Progression of the amyloidosis of the graft was confirmed by a
renal biopsy in 1993. Data published in the literature indicate that the survival
rate of amyloidotic graft recipients is worse than those of non-amyloidotic graft
recipients. This was confirmed in an analysis of the current CTS data which
showed an impaired survival rate at 5-yr of 66 +/- 4% (+/- SE) for patients with
amyloidosis (n = 413) as compared with 86 +/- 1% (p < 0.0001) for patients with
glomerulonephritis and 84 +/- 1 (p < 0.01) for patients with polycystic kidney
disease. Graft survival after 5 years was 55 +/- 4% in patients with amyloidosis
as compared with 63 +/- 1% (p = 0.02) in patients with glomerulonephritis and 68
+/- 1% in patients with polycystic kidney disease. Graft survival was improved in
amyloidotic patients treated with cylosporine as compared with patients on
steroids and azathioprine (55 +/- 4% vs. 38 +/- 8%, p < 0.05). It is concluded
that renal transplantation is the renal replacement therapy of choice for
patients with AA-type amyloidosis although the overall patient survival is
impaired in comparison with patients with other diseases.
PMID- 9642505
TI - Use of a donor aortic cross for arterial reconstruction of the
pancreaticoduodenal allograft.
AB - Combined liver-pancreas procurement generally requires back bench reconstruction
of the arterial blood supply with a donor Y-iliac graft to the pancreas graft. A
modified vascular reconstruction that uses donor aortic cross including the
brachiocephalic trunk and the left carotid artery as a single arterial patch is
presented. This is useful when iliac grafts are unavailable or are being used as
an alternative technique.
PMID- 9642506
TI - Post kidney transplant quality of life prediction models.
AB - Quality of life (QoL) is generally found to improve for renal transplant
recipients, although some patients continue to experience health-related
problems. It was within this context that we undertook our investigation which
focused on identifying the factors predictive of QoL following kidney
transplantation. METHODS: The sample included 91 non-diabetic patients of which
69 provided 6-month data and 68 provided 12-month data. Three QoL questionnaires
were administered to capture as many QoL dimensions as possible. Repeated measure
analyses of variance with multiple post hoc comparisons of LS means was conducted
to determine how QoL outcomes differed over time. Correlational analyses were
performed on the 12-month dataset to determine which variables to include in the
modeling process. Multiple stepwise regression with forward and backward entry
were used in the prediction modeling. RESULTS: Essentially all patients
experienced a significant improvement in QoL and the improvement occurred early
and appeared to be sustained. Five separate prediction models were constructed,
each including number of hospital days in first 6 months, employment, and social
support. CONCLUSIONS: The similarity of the five models is of note. It is not
necessarily these specific variables per se that predict QoL outcomes, but rather
what they conceptually represent. These findings provide direction for
interventions designed to enhance post-transplant QoL.
PMID- 9642507
TI - Patterns of acute rejection in portal-enteric versus systemic-bladder pancreas
kidney transplantation.
AB - Portal-enteric (PE) transplantation of the pancreas allograft provides maintained
physiologic drainage, and theoretically the portal delivery of transplantation
antigens may have beneficial effects on the graft acceptance leading to improved
graft survival. To determine whether the technique of pancreas placement affects
the incidence of acute rejection we reviewed our experience in technically
successful PE and systemic-bladder (SB) drained simultaneous pancreas and kidney
(SPK) transplants performed between 1989 and 1994. Forty-seven recipients were
included (SB = 30, PE = 17). All patients received cyclosporine based quadruple
immunosuppression and survived at least 1 month. The two groups were comparable
in HLA mismatches, cold ischemia time and level of immunosuppression at time of
rejection. In the SB group the incidence of rejection was 1.04 kidney
rejection/patient and 0.90 pancreas rejection/patient whereas the PE group
experienced 0.53 kidney rejection/patient and 0.47 pancreas rejection/patient.
The two groups were compared using incidence density statistics due to great
variation in follow-up time. The SB group had a significant higher density of
both kidney and pancreas rejections (p < or = 0.037 for kidney rejection and
0.058 for pancreas rejection). In addition, while 6 of 30 (20%) pancreas grafts
and 4 of 30 (13%) kidney grafts were lost to irreversible rejection in the SB
group, only 1 of 17 (6%) pancreas graft and 1 of 17 (6%) kidney graft were lost
in the PE group. These data demonstrate, that the PE placement of pancreas
allograft affects the rates of acute rejection and graft loss, and imply that
there exist some important immunological advantages when the pancreas graft is
drained into the portal circulation.
PMID- 9642508
TI - Usefulness of surveillance endomyocardial biopsy after pediatric cardiac
transplantation.
AB - Endomyocardial biopsy remains the 'gold standard' for the diagnosis of acute
rejection after cardiac transplantation, but few guidelines exist to determine
the indications for its use in pediatric cardiac transplant recipients. To
determine the usefulness of surveillance endomyocardial biopsy, 176 biopsies were
reviewed from 12 patients, aged 0.5-16 (average 9.7) yr, maintained on
cyclosporine, azathioprine and prednisone immunosuppression, and followed 2.8
45.5 (average 26.3) months after cardiac transplantation. Children old enough to
cooperate (n = 6) underwent biopsy on nine occasions in the first 6 months after
transplantation and quarterly thereafter. Children too young to cooperate (n = 6)
underwent biopsy with general anesthesia on four occasions in the first 6 months
after transplantation and every 6 months thereafter. Additional biopsies were
performed as warranted by symptoms or noninvasive tests. A new episode of acute
rejection was present in 13 biopsies (7%); continuing or resolving rejection in
19 others (11%). Remaining biopsies had no evidence of rejection (82 biopsies,
47%), had lymphocytic infiltrates insufficient for diagnosis (47 biopsies, 27%),
were inadequate for diagnosis (14 biopsies, 8%), or were consistent with ischemia
(1 biopsy, 0.5%). During the first 6 postoperative months, eight of 101 biopsies
were positive for rejection, three occurring on routine surveillance biopsy.
After 6 months, five of 75 biopsies showed a new episode of rejection, only one
occurring on routine surveillance biopsy. Based on this data, it is concluded
that: 1) episodes of rejection are relatively uncommon with triple drug
immunosuppression; 2) surveillance biopsies in the first 6 months after cardiac
transplantation may show unsuspected rejection; and 3) routine surveillance
biopsies more than 6 months after cardiac transplantation are unlikely to show
rejection in the absence of symptoms or other tests.
PMID- 9642509
TI - Infection and associated risk factors in the immediate postoperative period of
pediatric liver transplantation: a study of 176 transplants.
AB - OBJECTIVE: To describe the characteristics of infections occurring in the
immediate postoperative period of orthotopic liver transplantation (OLT) in
children in a pediatric intensive care unit (PICU) and the associated risk
factors. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary 16-bed
pediatric intensive care unit in a tertiary university hospital. PATIENTS: One
hundred and thirty-three pediatric patients (range 6M to 22 yr) who underwent 176
liver transplantations and were admitted to the pediatric intensive care unit for
at least 48 h. RESULTS: A total of 180 infectious episodes (IE) occurred in 78
(59%) patients who underwent 96 (54.5%) liver transplantations (1.35 IE/patient;
1.02 IE/transplantation). The mean stay was 15.4 +/- 1.1 d (mean +/- SD) and 22
patients died in the pediatric intensive care unit. One hundred and thirty-one IE
(72.8%) were bacterial, 31 (17.2%) fungal, and 14 (7.8%) mixed bacterial and
fungal. 39% of the IE appeared in the first postoperative week and 27% in the
second postoperative week. The most common sites of infection were abdomen
(48.3%) and blood stream (26.1%). Bacteria, alone or with fungi, were present in
145 IE (1.1 IE/patient). Gram-positive aerobic bacteria (63%) predominated over
gram-negative bacteria (54%) and fungi. Fungi were present in 45 IE; 53.4% of the
infections occurred in lung (73% yeasts). The risk factors for infection that
were identified were related with younger age, lower body weight, longer cold
ischemia time, partial graft, and the volume of packed red blood cell
transfusions. Infected patients had more postoperative complications and longer
stay in the PICU (21 +/- 16 vs. 8 +/- 6 d), but no increase in mortality. The
risk of infection increased 2.38 times with partial grafts and 1.1 times with
each intraoperative transfusion of 20 ml/kg of packed red blood cells (RBC).
CONCLUSIONS: Infection in the immediate postoperative period of pediatric OLT was
related with a high morbidity but was not related significantly with increased
mortality. The main risk factors for infection in the postoperative period of OLT
were related essentially with small recipient size and the inherent complexity of
the operation. Routine oropharyngeal decontamination is recommended, as well as
early administration of oral nystatin in preoperative intestinal decontamination.
The risk of infection increased 2.38 times with partial grafts and 1.1 times with
the transfusion of every 20 ml of packed RBC.
PMID- 9642510
TI - Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated
with mycophenolate mofetil combined with low cyclosporine and steroid doses.
AB - Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids
doses efficiently prevents acute rejection in kidney transplants. However, this
regimen has been associated with an increased incidence of cytomegalovirus (CMV)
disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting
that the combination of two powerful immunosuppressants carries the risk of
overimmunosuppression. For this reason, we treated a group of patients with MMF 3
g/d combined with low cyclosporine and steroids doses. Eighty-two kidney
transplants performed at two centers and enrolled in the European Mycophenolate
Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF
2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all
patients received cyclosporine and steroids at conventional doses. Fifteen kidney
transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3
g/day combined with low cyclosporine and steroid doses (group D). Efficacy was
evaluated as the incidence of biopsy proven acute rejection, and safety focused
on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of
biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C
had a high incidence of CMV disease (35.7%) when compared with the other groups
(lower than 8%). Incidence of leukopenia was higher in patients treated with MMF
(B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%).
Patients in group (C) displayed leukopenia mainly in the context of CMV disease,
while patients of group (D) had leukopenia not related to CMV infection. All
patients of group (D) who presented leukopenia recovered after MMF reduction
dose, while in group (C) there were 5 out of 28 patients who required MMF
withdrawal. We propose that a reasonable approach to take advantage of a powerful
non-nephrotoxic immunosuppressant such as MMF, could be the administration of
this drug at 3 g/d from the time of transplantation combined with low CsA and
steroid doses.
PMID- 9642511
TI - Procalcitonin in the early phase after renal transplantation--will it add to
diagnostic accuracy?
AB - The determination of serum procalcitonin (PCT) was tested for its utility in
detecting invasive bacterial infection and acute rejection during the first 6 wk
after kidney transplantation. Fifty-seven kidney graft recipients were
prospectively included in the study. In 13/57 patients, 16 episodes of acute
biopsy-proven rejection occurred and were treated with high-dose steroids (n =
14) or with OKT3 (n = 2). Seventeen out of 57 patients experienced 19 invasive
bacterial infections; 2/57 had partial graft necrosis due to malperfusion. Twenty
five out of 57 graft recipients experienced an uncomplicated postoperative
course. A total of 116 samples were analyzed and the following data obtained:
PCT, C-reactive protein (CRP), white blood cell (WBC) count, corresponding body
temperature and serum creatinine. Procalcitonin values for patients with
rejection did not differ significantly from those of the healthy transplant
recipients (p = 0.47). In contrast, PCT was clearly elevated with invasive
bacterial infection or partial graft necrosis (p < 0.01). OKT3 treatment of
rejection led to a more than 10-fold increase in PCT. C-reactive protein, unlike
PCT, was elevated to a variable extent in patients with graft rejection, though
CRP values were significantly more elevated in patients with infection than in
those with rejection (p < 0.01). The specifity for detection of invasive
bacterial infection was 0.7 for PCT and 0.43 for CRP, whereas sensitivity was
0.87 for PCT and 1.0 for CRP. There was no correlation between PCT and serum
creatinine (r = 0.06). Haemodialysis did not lower PCT serum concentrations.
Procalcitonin values rose postoperatively to peak levels on the first and second
days and mostly declined to normals within 1 wk. In conclusion PCT, not being
influenced by acute kidney graft rejection but serving as a specific indicator of
systemic bacterial infection, could help to discriminate between both types of
inflammation.
PMID- 9642512
TI - Increased intragraft IL-15 mRNA expression after liver transplantation.
AB - To study T-cell/macrophage interactions at the molecular level in clinical
allograft rejection, we measured intragraft mRNA expression of the T-cell derived
cytokine IL-2 and the macrophage derived chemokine IL-15, a novel cytokine
associated with T-cell activation, in post-transplant liver biopsies (n = 33) and
in non-transplanted control liver tissue by reverse transcriptase-polymerase
chain reaction (RT-PCR). We analyzed biopsies without evidence of rejection (n =
12), with spontaneously resolving histological rejection (n = 10), or with
histological rejection accompanied with clinical rejection (n = 11) defined by
rising serum bilirubin and aspartate amino transaminase levels. IL-15 mRNA
expression was present in the majority of post-transplant liver biopsies (91%,
30/33) and was significantly upregulated as compared with non-transplanted liver
tissue (p = 0.005). However, the increased intragraft IL-15 mRNA level was not
indicative for rejection. In contrast to intragraft IL-15 mRNA expression, IL-2
mRNA transcription was measured in the minority of the post-transplant liver
biopsies (15%, 5/33) and not detectable in control specimens. In addition, IL-2
mRNA was almost specifically measured in rejection biopsies concurrent with graft
dysfunction (36%, 4/11 versus 1/22 without clinical rejection; p = 0.03). No
relation between intragraft IL-2 and IL-15 mRNA expression was found. The IL-15
mRNA expression levels were not higher in the IL-2 negative rejections compared
with those in IL-2 positive rejections. To conclude, in contrast to IL-2, the
function of IL-15 in T-cell mediated rejection remains unclear. The overall high
IL-15 mRNA levels in sites of immune responses suggests that the macrophage
derived mediator IL-15 is involved in a constant flow of T-cells from the
circulation into the graft.
PMID- 9642513
TI - Apoptosis and hepatic allograft reperfusion injury.
AB - Necrosis and apoptosis are distinct, but nonexclusive mechanisms of cell death.
Until recently, investigators have focused upon necrosis as the sine qua non of
lethal cell injury. Specifically, within the realm of liver transplantation,
preservation strategies dealing with ischemia/reperfusion injury have
concentrated upon minimizing the biochemical and histologic correlates associated
with necrosis. Little is known of the role of apoptosis in reperfusion injury in
human liver transplantation. Post-reperfusion liver biopsies from 35 patients
were retrospectively analyzed for histologic evidence of necrosis. Apoptosis was
identified histologically and using a chromogenic technique of in situ labeling
of fragmented DNA. The number of apoptotic cells increased in parallel with the
necrosis reperfusion score in a significant fashion (p = 0.003 by ANOVA). There
was not a Zone 1, 2 or 3 predominance to the histologic distribution of apoptotic
cells. The recipient peak serum transaminase values were also noted to increase
with the reperfusion score (p = 0.001 by ANOVA). These results suggest that: 1)
apoptosis occurs in the setting of reperfusion injury during human orthotopic
liver transplantation (OLT); and 2) the extent of apoptosis increases in parallel
with pathologic and biochemical parameters of reperfusion injury. Given the
distinct nature of apoptosis and the highly regulated and conserved pathway for
its initiation, inhibition of apoptosis with specific molecular targets, may
serve to decrease allograft reperfusion injury.
PMID- 9642514
TI - Serum lipase as a marker for pancreatic allograft rejection.
AB - In patients with enteric drainage of pancreas transplants, urinary amylase cannot
be used as a marker of rejection. Since most of the patients in our center have
enteric drainage, the aim of this study was to evaluate serum lipase as a
potential marker for rejection. From July 1994 to March 1997, 100 patients
underwent pancreas transplantation with enteric (78) or bladder (22) drainage.
Forty-two of the 100 patients had both daily serum lipase (sLip) values and
either kidney core or fine needle aspiration biopsies of the pancreas and/or
kidney. Thirty-one of the 42 had biopsy proven rejection and were treated on day
0 (D0). From day -7 (D -7) to day +7 (D +7), sLip, serum amylase (sAmy), fasting
blood sugar (FBS) and serum creatinine (sCr) were measured daily. Serum lipase
values rose from 322 +/- 107 IU/L on D -2 to 634 +/- 247 IU/L on D -1 (p =
0.0203) in 22 of the 31 patients with biopsy proven rejection (sensitivity 71%).
The rise in sCr in combined kidney pancreas transplants with biopsy proven
rejection was a better marker than sLip (sensitivity 86%). The sensitivity of
sAmy and FBS was 50 and 33%, respectively. Other than sCr, sLip appeared to be
the best marker for acute rejection in enterically drained pancreas transplants
which should be useful as a non-invasive indicator of rejection in solitary
pancreas transplants where sCr cannot be used.
PMID- 9642515
TI - Orthotopic liver transplantation for hepatic associated metabolic disorders.
AB - Hepatic associated metabolic disorders represent 5% of the indications for
orthotopic liver transplantation (OLTX) according to the European Liver
Transplant Registry. We studied the outcome of this group at our institution
after OLTX and combined liver/kidney transplantation. Between September 1988 and
January 1997, 837 OLTXs were performed in 735 patients. Patient survival and
graft function at 1 yr were 91.3 and 86%, respectively. Thirty-nine OLTXs were
performed in 38 patients (15 female/23 male, median age +/- SD: 35 +/- 14 yr,
range 4-60 yr) due to liver associated metabolic disorders (4.7%). Indications
included Wilson's disease (n = 14), alpha-1-anti-trypsin-deficiency (n = 7),
hemochromatosis (n = 4), erythropoetic protoporphyria (n = 4), cystic fibrosis (n
= 2), Crigler-Najjar syndrome type I (n = 1), glycogenosis type I (n = 1),
ornithine-transcarbomylase-deficiency (n = 1). In addition 4 patients suffering
from primary hyperoxaluria type I received combined liver/kidney grafts. Survival
rate the 1 yr after OLTX and combined OLTX/NTX was 91.8%. Twenty patients
received cyclosporin A (55%) and 17 patients tacrolimus (45%) as primary
immunosuppression. The mean follow-up was 28.6 months (range 4-73 months). Two
patients with hemochromatosis died 1 and 3 months after OLTX, respectively, from
Aspergillus sepsis followed by multiorgan-failure. One patient died of malignant
lymphoma 5 months after transplantation. One patient required retransplantation 2
months after OLTX following arterial thrombosis and ischemic type biliary lesion.
One year after OLTX, all patients demonstrated good graft function, liver grafts
(ALT 17.9 +/- 13.6 IU/L, bilirubin 0.8 +/- 0.3.mg/dl, thromboplastin time 94 +/-
15%), and combined liver/kidney grafts (creatinine 2.4 +/- 1.4 mg/dl). OLTX,
respectively combined OLTX/NTX, represent a successful therapy for hepatic
associated metabolic disorders. Survival rates and graft function are similar to
those in liver graft recipients for established indications at our institution.
OLTX seems to be an excellent treatment for hepatic based therapy resistant
neurological disorders.
PMID- 9642516
TI - Long-term quality of life after kidney and simultaneous pancreas-kidney
transplantation.
AB - We are using a validated questionnaire (SF-36) to annually assess health-related
quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF
36 consists of eight scales to assess physical functioning, general health, and
mental functioning. Norms and 95% confidence intervals (C.I.) have been developed
for the US population. At present, 1138 recipients with functioning grafts (520
Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the
questionnaire. Of the recipients, 446 completed the questionnaire once; 632
twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206
after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125
after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there
was little change in average scores for each scale between years (p = NS). In
relation to the US population, average scores for nondiabetics were below the
50th percentile on all 8 scales; for diabetics < 25th percentile on the physical
functioning and vitality scales, < 50th percentile on all others. For both
diabetic and nondiabetic recipients, average scores were higher than reported
norms for patients with CHF, COPD, or depression but were similar to those with
Htn or recent MI. Individual scores were then compared with age-matched means (+/
2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to
40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95%
C.I. on individual scales (particularly the physical functioning and general
health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had
scores on the physical functioning scales below the 95% C.I. More diabetic
recipients (vs. nondiabetics) reported poor QOL on the physical functioning,
general health and social functioning scales. There was little difference in the
mental health scales. For those with Type I diabetes, a similar percentage of
kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched
population, except on the GH scale (better QOL for K/P recipients). We conclude
that successful transplant recipients report health-related QOL below that of the
age-matched general population but similar to those with other chronic diseases.
Diabetic and nondiabetic recipients have similar scores on the mental health
scales; nondiabetic recipients score better on the general health and physical
functioning scales.
PMID- 9642517
TI - Two-hour cyclosporine level determination is the appropriate tool to monitor
Neoral therapy.
AB - To assess the safety profile of Neoral dose adjustment using cyclosporine (CsA)
trough levels (C0) compared with levels obtained 2 h after the morning dose (C2),
30 stable adult heart transplant patients 1 yr or more after surgery were
converted from Sandimmune to Neoral. After a baseline visit (before conversion),
initial follow-up included two visits (2 and 4-6 wk after conversion). After the
first visit, patients were randomized to Group I (C0: 100-200 ng/ml) or Group II
(C2: 200-400 ng/ml). Abbreviated pharmacokinetics were obtained for the
estimation of the AUC0-4 h. Renal function was assessed by serum creatinine and
the cimetidine-modified creatinine clearance. C2 correlated better than C0 with
the AUC0-4 h (r = 0.91 vs. 0.63). Initial Neoral dose (mg/kg/d) was similar in
both groups (2.8 +/- 0.5 and 2.8 +/- 0.8), and was lower in Group II at the
second visit (2.0 +/- 0.7 vs. 3.0 +/- 0.6, p = 0.0001). C2 levels decreased in
Group II from 912 +/- 438 to 555 +/- 271 ng/ml (p = 0.01), without evidence of
acute rejection on endomyocardial biopsies. After the second visit,-both groups
were monitored with C2, and the range was increased to 300-600 ng/ml. At the last
visit (additional follow-up of 5 +/- 1 months), Neoral dose (mg/kg/d) was reduced
to 2.0 +/- 0.3 in Group I (p < 0.001) and 1.8 +/- 0.4 in Group II. Serum
creatinine was lower in Group II at the second visit (138 +/- 59 vs. 168 +/- 37
mumol/L, p = 0.01) and was similar in both groups at the last visit. Neoral dose
reduction based on C2 levels was not associated with acute rejection. The better
correlation with the AUC0-4 h suggests that C2 may be more reliable than C0 for
Neoral dose adjustment.
PMID- 9642518
TI - Making sense of kidney transplantation: a view from African recipients.
AB - This study investigated the experiences of African patients who have undergone a
kidney transplant within the past 10 yr, either from a live donor or from a
cadaver. Little is known about kidney transplantation among African patients, in
particular about psychological and social responses to the process. The study
examined how these patients made (and still make) sense of the transplant
experience, and hence attribute a particular subjective meaning to the factors
and variables which have been at play during the course of the transplant. Semi
structured interviews were conducted with 14 African patients (8 women and 6
men), from the Renal Unit of Groote Schuur Hospital, Cape Town. The interviewees
were selected from the records of the Unit. Several themes accounted for the
frameworks of meaning that patients attributed to the transplant process. These
are: religion and indigenous belief systems; the role of the extended family;
patients' respective routes to the hospital; feelings about the transplant; and
experiences in the hospital.
PMID- 9642519
TI - Effects of low-dose dopamine on urine output in oliguric, critically ill, renal
transplant patients.
AB - Low-dose dopamine (LD-DA) has been used extensively to increase urine output (UO)
in critically ill patients. These effects have recently been documented in
patients with normal and mildly abnormal renal function. The purpose of this
study was to quantitate the effects of LD-DA on UO and urineNa (UNa) excretion in
renal transplant (RT) patients, and thereby evaluate the effects of LD-DA on the
denervated kidney. METHODS: Five RT patients and 7 non-transplant controls,
hospitalized in the surgical intensive care unit (SICU), with serum creatinine
(serum Cr) < 2 mg/dL who were oliguric (UO < 0.5 mL/kg/h), received LD-DA (2.5
micrograms/kg/min). None received other diuretics within 12 h, and all had
pulmonary artery occlusion pressure (PAOP) > 10 mmHg and CI > 3.0 L/min/m2. UO
was measured hourly and averaged for 2 h pre and 6 h during LD-DA. All data are
mean +/- SD. RESULTS: APACHE II (14 +/- 4), CI (4.1 +/- 1.2 L/min/m2), PAOP (15
+/- 4 mmHg), HR (98 +/- 16/min), and MAP (83 +/- 10 mmHg) were similar between
groups and did not change during LD-DA therapy. Initial serum Cr in the RT group
(1.6 +/- 0.4 mg/dL) was greater than that in controls (0.9 +/- 0.24 mg/dL), p <
0.05. Initial UO [0.26 +/- 0.10 mL/kg/h (RT) and 0.31 +/- 0.12 mL/kg/h
(controls)] and initial UNa [8 +/- 62 meq/L (RT) and 54 +/- 28 meq/L (controls)]
were not different. Urine output increased significantly compared with baseline
in both groups [final UO 0.55 +/- 0.14 mL/kg/h (RT) and 0.96 +/- 0.41 mL/kg/h
(controls)]. Final UNa [72 +/- 37 meq/L (RT) and 99 +/- 56 meq/L (controls)] were
not different from each other or from baseline. CONCLUSIONS: LD-DA increases UO,
but not UNa excretion, in RT patients with oliguria, comparably to controls.
These data suggest that this effect is predominantly mediated by dopaminergic
receptors, since the transplanted kidney is denervated and there were no
significant associated changes in hemodynamic parameters during the study.
PMID- 9642520
TI - Suggested guidelines for the use of tacrolimus in pancreas/kidney
transplantation.
AB - As experience with tacrolimus (FK506, Prograf) accumulates and reduced rejection
rates are increasingly demonstrated, some transplant centers are adopting
tacrolimus-based primary immunosuppressive regimens for their patients undergoing
pancreas/kidney transplantation. The guidelines provided in this article based on
the experience of four major US transplant centers, cover issues related to
dosing, blood levels, concomitant use of mycophenolate mofetil (MMF), antifungal
and antiviral prophylaxis, and drug interactions. For post-transplant
immunosuppression some centers initiate oral tacrolimus administration on
postoperative day 1, 2, or 3, while others wait until day 6 or 7, when renal or
gastrointestinal function has resumed. Most centers endeavor to achieve higher
target trough levels (approximately 10-20 ng/mL, but not higher) in the first 3
months post-transplant, reducing levels thereafter. Several centers are now using
MMF instead of azathioprine as an adjunct to tacrolimus. Conversion from
cyclosporine to tacrolimus during maintenance therapy is often considered in the
event of rejection or when adverse events do not respond to dosage reduction.
PMID- 9642521
TI - Liver transplantation in hyponatremic patients with emphasis on central pontine
myelinolysis.
AB - Patients awaiting liver transplantation may suffer from severe hyponatremia. It
has been suggested that hyponatremia or its treatment might be associated with
central pontine myelinolysis (CPM), a serious complication that can be seen after
orthotopic liver transplantation (OLT). We undertook this study to assess the
outcome of hyponatremic patients after OLT and to evaluate the risk factors in
the development of CPM. A total of 379 adult OLT performed in 347 patients
between March 1993 and December 1995 was studied using a prospectively-collected
data base and retrospective chart review. The following risk factors for the
development of CPM were analyzed: primary liver disease, nutritional status,
alcoholism, diuretic use, hepatic encephalopathy, United Network for Organ
Sharing (UNOS) status, preoperative serum sodium, magnesium and cholesterol
levels, increase in serum sodium concentration during surgery, and
immunosuppressive treatment. Overall 12 patients (3.5%) underwent OLT in a
hyponatremic state (serum sodium < or = 127 meq/L). At a median follow-up of 14
months, 8 patients were alive without any neurological sequel. Six of the 12
patients developed neurological complications in the early post-operative period
including CPM in 3, confusion in 2, and seizure in 1. The 3 patients who
developed CPM expired within 3 months of OLT. The changes in serum sodium
concentration during OLT in patients with and without CPM were 20.7 +/- 8.1 and
7.0 +/- 5.1 meq/L, respectively (p = 0.005). No other risk factor could be
identified in the development of CPM. It is concluded that prognosis of
hyponatremic patients after OLT is poor if they develop CPM. Slow correction of
hyponatremia perioperatively may be critical in preventing this devastating
complication.
PMID- 9642522
TI - Maintenance therapy with oral ganciclovir after treatment of cytomegalovirus
infection.
AB - While oral ganciclovir (OGCV) has been used as primary prophylaxis in patients at
high risk for cytomegalovirus (CMV) infection after solid organ transplantation,
its value in secondary prophylaxis is unknown. We have examined the use of OGCV
as maintenance therapy following confirmed CMV infection on 16 occasions in 15
patients, in kidney (n = 4), kidney-pancreas (n = 3) lung (n = 6) and heart-lung
(n = 1) recipients. OGCV was used in two distinct clinical situations. One group
(n = 7) received OGCV as consolidation therapy (mean duration of 21 +/- 5 d)
following i.v. ganciclovir induction therapy (mean duration of 16 +/- 5 d) for
acute CMV infection, and sustained remission was achieved in 6/7 patients for a
median follow-up of 300 d. In the second scenario, OGCV suppressed clinical
disease in all patients with relapsing CMV infection (n = 9), with minimal or
absent toxicity with a median follow-up of 152 d. OGCV reduced morbidity by
allowing removal of central lines used for long-term i.v. therapy in patients
with poor peripheral access. Hence, this study demonstrates the safe and
effective use of OGCV as consolidation therapy after standard induction treatment
with i.v. ganciclovir, and as long-term suppressive therapy in transplant
recipients with recurrent CMV infection.
PMID- 9642523
TI - Disseminated histoplasmosis in a patient after orthotopic liver transplantation.
PMID- 9642524
TI - Acute acalculous cholecystitis (AAC) resulting in gallbladder perforation in a
solid organ transplant recipient: a case report.
AB - Gallbladder perforation is a frequent complication of acute acalculous
cholecystitis (AAC), resulting in substantially increased morbidity and
mortality. Two groups of patients are at increased risk for perforation: those
with systemic diseases (especially peripheral vascular disease, intrinsic heart
disease, or diabetes) and those who are chronically immunosuppressed. The current
population of solid organ transplant recipients meets both criteria. We describe
an unusual case of gallbladder perforation as a complication of AAC in an
otherwise healthy kidney transplant recipient. Because transplant recipients are
at increased risk for gallbladder perforation, maintaining a high index of
suspicion for this complication will help avoid the increased morbidity and
mortality associated with this diagnosis.
PMID- 9642526
TI - History of iatrogenic disease.
PMID- 9642525
TI - A liver with polycystic liver disease as graft for orthotopic liver
transplantation.
AB - Donor organ shortage calls for widening of criteria for organ transplantation. In
exceptional cases, even livers with macroscopic alterations may be accepted for
transplantation. The case of a patient who received a liver graft from a donor
with previously unknown adult polycystic degeneration is reported. The liver
showed only small bilobar cysts with less than 10% of hepatic replacement and was
successfully used for orthotopic liver transplantation. Two years after
transplantation the patient is in good clinical condition and has returned to
work.
PMID- 9642527
TI - Drug-induced lichen planus.
PMID- 9642528
TI - Drugs in exacerbation and provocation of psoriasis.
PMID- 9642529
TI - Drug-induced scleroderma and sclerodermiform conditions.
PMID- 9642530
TI - Drug-induced lupus erythematosus.
PMID- 9642531
TI - Drug-induced pemphigoid: bullous and cicatricial.
PMID- 9642532
TI - Drug-induced linear immunoglobulin-A bullous dermatosis.
PMID- 9642533
TI - Drug-induced pemphigus.
PMID- 9642534
TI - Drug-induced toxic epidermal necrolysis.
PMID- 9642535
TI - Current opinions in headache pathogenesis: introduction and synthesis.
PMID- 9642536
TI - Cluster headache: imaging and other developments.
AB - Cluster headache, one of the most severe pain syndromes in humans, is usually
described as a vascular headache. However, the striking circadian rhythmicity of
this strictly unilateral pain syndrome cannot readily be explained by the
vascular hypothesis. Recent studies using positron emission tomography suggest
that a central nervous system dysfunction in the region of the hypothalamus is
the primum movens in the pathophysiology of cluster headache. From a
physiological viewpoint, therefore, cluster headache should be described as a
neurovascular headache, thus placing equal emphasis on its fundamental
pathophysiology and clinical expression.
PMID- 9642537
TI - Brain excitability in migraine: evidence from transcranial magnetic stimulation
studies.
AB - Central neuronal hyperexcitability is proposed to be the putative basis for the
physiologic disturbances in migraine. Because there are no structural
disturbances in migraine, only physiologic studies can provide insight into the
underlying mechanisms. Recently, transcranial magnetic stimulation has been
developed as a valuable research tool and can be used to study brain function
noninvasively. This article is a review of the studies done in migraine using
transcranial magnetic stimulation.
PMID- 9642538
TI - Current status of genetic discoveries in migraine: familial hemiplegic migraine
and beyond.
AB - Familial hemiplegic migraine (FHM) has been related to mutations in a brain
calcium channel gene among Chr19p linked FHM families. Subsequent genetic Studies
in different FHM families showed that additional causative genes must reside in
other regions of the genome, including the long arm of Chromosome 1. Parallel
discoveries in mouse mutants involving ion channel genes have also accelerated
our understanding of the spectrum and functional significance of the CNS-related
ion channel disorders. These studies have clear implications for migraine,
epilepsy, and ataxia. An association study was suggested that other
'susceptibility' genes like the dopamine DRD2 receptor will be important in
characterizing the genetic components of the larger, heterogeneous group of
migraine disorders.
PMID- 9642539
TI - The place of migraine as a channelopathy.
AB - Over the past 8 years an increasing awareness of the role of mutant ion channels
in episodic diseases of humans has emerged. The importance of these discoveries
is now being extended to a growing list of membrane excitability disorders of the
nervous system. Molecular characterization of episodic diseases that are rare and
monogenic will ultimately shed light on more common and complex disorders, such
as epilepsy and migraine.
PMID- 9642540
TI - Recent advances in mechanisms of spreading depression.
AB - Although spreading depression has been known for over 50 years, recent research
into this interesting experimental phenomenon provides evidence for an
integrative role of spreading depression in brain pathophysiology. Spreading
depression activates neurophysiological pathways that may have widespread
consequences on brain function, but depends on the basal energy state of the
brain.
PMID- 9642541
TI - Inflammatory myopathy in myasthenia gravis.
PMID- 9642542
TI - Chronic inflammatory diseases of the nervous system.
AB - In many neurologic diseases, activated leukocytes enter the nervous system and
initiate a chronic inflammatory process. Understanding how the cellular and
humoral responses are associated with pathogenesis is essential for the
formulation of a unifying model of central and peripheral nervous system
inflammation. Based on such a model, immunotherapeutic strategies and protocols
can be designed.
PMID- 9642543
TI - Central nervous system vasculitis.
AB - Central nervous system vasculitis occurs in a variety of clinical settings. Some
exhibit a distinct age preference; others a tissue tropism. Most frequently
encountered are giant cell arteritis (temporal arteritis) and vasculitis
secondary to infections. The central nervous system may be involved in the
antineutrophil cytoplasmic antibody-associated systemic vasculitides and
occasionally neurologic abnormalities appear as a presenting manifestation of
disease. Isolated angiitis of the central nervous system, a rare form of
vasculitis that is restricted to the central nervous system, must be
distinguished from other causes of central nervous system inflammation and from
noninflammatory vascular disease. We are learning a great deal about the cellular
mechanisms of vascular inflammation in general. Some manifestations of the
clinical disease result from histologic features of the infiltrate and the size
of affected vessel. However, the local consequences of inflammation, such as
increased coagulation and altered vasomotor tone, as well as the systemic
consequences, such as activation of the central noradrenergic systems,
trigeminovascular system, and hypothalamic pituitary adrenal axis, contribute
both to pathogenesis of disease and to recovery.
PMID- 9642544
TI - Neurological involvement in systemic lupus erythematosus.
AB - The aetiology of neurological involvement in systemic lupus erythematosus (SLE)
still remains largely uncertain, but there are some recent reports of retrovirus
activity linked to human and mouse models of SLE. Antiribosomal P antibodies
appear specific to SLE and tend to be associated with psychiatric disease, but
not exclusively so. The role of antiphospholipid antibodies in the pathogenesis
of SLE may not be solely to cause thrombotic events, but also to act directly on
neuronal tissue. The importance of another group of antibodies, those against
Beta 2 glycoprotein I, a phospholipid binding protein, is now being recognized.
Amongst the many neurological manifestations of SLE, cognitive impairment is
becoming increasingly recognized and appears not to be simply a response to
chronic disease or its treatment. Of the newer imaging techniques applied to SLE,
positron emission tomography has proved inconsistent and somewhat disappointing
but single photon emission computed tomography in active disease appears more
sensitive compared to MRI, although it still remains a nonspecific technique. The
treatment of SLE remains disappointing and no controlled trials for neurological
disease have been published to date but a number of experimental approaches do
offer hope for the future.
PMID- 9642545
TI - Lyme neuroborreliosis.
AB - A broad variability in the clinical manifestations is observed in the European
and North American borrelioses. This is dependent on bacterial strain differences
in virulence and organotropism, and on different immune responses to Borrelia
burgdorferi of the host in these areas. Experimental neuroborreliosis has given
insights into mediators and molecular mechanisms of inflammation induced by B.
burgdorferi. Histopathological investigations have described the different
patterns of injury in the peripheral and central nervous systems. The classic
symptoms of neuroborreliosis have been supplemented by new clinical syndromes and
neuropsychological investigations. In clinical trials, the efficacy and cost
effectiveness of recommended oral and intravenous antibiotic therapies have been
compared in early Lyme disease, arthritis and acute disseminated Lyme disease.
PMID- 9642547
TI - Headache.
PMID- 9642548
TI - Inflammatory diseases.
PMID- 9642546
TI - New variant Creutzfeldt-Jakob disease.
AB - New variant Creutzfeldt-Jakob disease is a novel human prion disorder with
characteristic clinical and neuropathological features, which results from
exposure to the bovine spongiform encephalopathy agent. The probably lengthy
incubation period makes it difficult to predict future new variant Creutzfeldt
Jakob disease case numbers; further studies are required to clarify risk factors
and the potential for human spread.
PMID- 9642549
TI - Age degradation in top-down processing: identifying objects from canonical and
noncanonical viewpoints.
AB - Twenty-four young (mean age 21.8 years) and 24 old (mean age 65.2 years)
participants were asked to determine whether spoken words correctly named
pictures of objects. Half of the objects were portrayed from noncanonical
(unusual) viewpoints, and half were portrayed from canonical viewpoints. The
older participants required more time and made more errors when they evaluated
the noncanonical pictures (relative to the canonical pictures) than the younger
participants. This finding is consistent with previous evidence that frontal lobe
function degrades with aging and with results from a positron emission tomography
study (S. M. Kosslyn et al., 1994) that showed that the frontal lobes (among
other areas) are activated more in the noncanonical condition than in the
canonical condition.
PMID- 9642550
TI - The relationship of cortisol to practice-related gains in intelligence among
older persons.
AB - Based on data collected from two separate samples of older adults, the present
study explored the role of cortisol in mediating practice-related gains in fluid
intelligence (Gf) among older adults. Analyses across samples involved treatment
group participants who received stress inoculation training in order to reduce
anxiety concerning intellectual performance; waiting list control group
participants did not receive training until the experiment(s) were completed.
Practice effects were examined for both groups. In Study 1, the sample consisted
of a heterogeneous (re: concerns about intellectual performance) group of older
adults, and Study 2 participants were older adults who self-reported as being at
least moderately anxious or concerned about intellectual performance declines.
The two samples differed on health (p < .01), with Study 2 participants being
healthier (as determined via self-report). Results indicated that practice, but
not training, effects were evident for measures of crystallized ability (Gc) and
Gf across both studies. The data also suggested that cortisol mediation was
different for the two samples in that it was negatively correlated with Gf in the
first sample, and, though not significant, positively correlated with Gf in the
second. The same directional relationships were evident for the measure of Gc.
Comparisons between studies regarding correlations between cortisol and practice
related gains in performance were significant for Gf (p < .01) and approached
significance for Gc (p < .07). These data seem to suggest that for some older
persons, higher levels of cortisol interfere with the effects of practice on Gf
performance, while for others, higher cortisol facilitates such gains in
performance.
PMID- 9642551
TI - The influence of list format and category headers on age differences in
understanding medication instructions.
AB - We examined whether instructions are better understood and remembered when they
contain organizational cues. Our previous research found that older and younger
adults organize medication information in similar ways, suggesting that they have
a schema for taking medication. In the present study, list formats (vs.
paragraphs) emphasized the order of information and category headers emphasized
the grouping of information specified by this schema. Experiment 1 examined
whether list and header cues improve comprehension (answer time and accuracy) and
recall for adults varying in age and working memory capacity (measured by a
sentence span task). List instructions were better understood and recalled than
paragraphs, and reduced age differences in answer time and span differences in
accuracy. Headers reduced paragraph comprehension for participants with lower
levels of working memory capacity, presumably because they were not salient cues
in the paragraphs. Experiment 2 investigated if headers were more effective when
more saliently placed in paragraphs and lists, and if list and header cues helped
readers draw inferences from the instructions. List formats again reduced age
differences in comprehension, especially reducing the time needed to draw
inferences about the medication. While headers did not impair comprehension,
these cues did impair recall. The present study suggests that list-organized
instructions provide an environmental support that improves both older and
younger adult comprehension and recall of medication information.
PMID- 9642552
TI - Visual and Haptic influences on memory: age differences in recall.
AB - Older (age 60-75) and younger adults (age 20-35) participated in a within-subject
experiment. All participants were given four lists of 17 items, a recall test
followed each list. Each participant was given a separate list under each of the
following conditions, at the rate of 1 item every 10 s. (1) control: list of
nouns; (2) visual-only: visually shown objects; (3) visual-and-haptic: given
objects to hold and visually examine; (4) haptic-only: blindfolded, given objects
to hold. A final surprise recall test was given of all items presented in the
study. Data indicated that younger adults recalled more than older adults under
all conditions. However, both age groups had the highest recall under the haptic
conditions.
PMID- 9642553
TI - The effect of age on the learning of a nondeclarative category classification
task.
AB - A category classification task was administered to participants in their twenties
through their eighties. Participants studied a set of high distortions of a
prototype dot pattern and were then asked to choose whether or not a new set of
dot patterns (random patterns, high distortions, low distortions, and the
prototype) belonged to the same category of dot patterns as studied. Participants
were also administered a recognition test after studying a second set of dot
patterns. There were no significant differences for age groups on the pattern
recognition test. In 2 of the 3 analyses of the category classification task,
there were no significant age effects. However, there was a small age effect in
one analysis with the young making more accurate classifications on two aspects
of the task. The results are consistent with the view that small age-related
effects may exist for some tests of nondeclarative memory.
PMID- 9642554
TI - The influence of aging and target motion on the control of prehension.
AB - The purpose of this study was to examine age-related differences in reaching
behavior when younger (mean age = 26.0 years) and older (mean age = 70.1 years)
individuals were required to reach toward and grasp both small and large targets
that were either stationary or moving. The older subjects had shorter movement
times, and smaller within-subject movement time variability than younger
subjects. Also, the deceleration of the reach was shorter for older subjects,
indicating that they were not making extensive use of on-line feedback, and were
instead utilizing anticipatory control strategies. There were no age differences
in the size of the maximum grasp around the target, but the timing of the grasp
was influenced by target motion for the younger subjects, suggesting on-line
control for the younger subjects only.
PMID- 9642555
TI - [Tumescence local anesthesia. Improvement of local anesthesia methods for
surgical dermatology].
AB - The tumescent technique of local anesthesia was developed by J. Klein ten years
ago to facilitate liposuction surgery. Tumescent anesthesia not only became the
standard technique for liposuction, but proved to be of great value for other
surgical problems in dermatology. Meanwhile, several noncosmetic uses for
tumescent anesthesia were pioneered by dermatologic surgeons. This first review
of the tumescent technique in German literature will focus on its specific
advantages and disadvantages when applied in different fields of dermatologic
surgery. Our own experience will be discussed, as well as future developments.
PMID- 9642556
TI - [Coincidence of scleroderma and primary biliary cirrhosis. Results of a
systematic study of a dermatologic patient sample].
AB - We present for the first time in the German dermatologic literature results of
systematic investigations on the relationship between scleroderma,
antimitochondrial autoantibodies and primary biliary cirrhosis (PBC). 40 patients
with different clinical pictures of systemic and localized scleroderma were
examined. By means of indirect immunofluorescence technique, in the sera of 5
cases (12.5%) antimitochondrial autoantibodies (AMA) could be detected. The
target autoantigens for the AMA were identified as pyruvate dehydrogenase,
branched-chain alpha-ketoacid dehydrogenase, alpha-ketoglutarate dehydrogenase,
protein x and pyruvate dehydrogenase E-1 alpha in all 5 cases, PBC was confirmed
by means a liver biopsy and endoscopic retrograde cholangioscopy. Considering the
occurrence in the normal population, the prevalence of the PBC in our scleroderma
collective was 8.3 x 10(2) to 2.5 x 10(3) x higher. In respect to the clinical
picture of the scleroderma, we found a M2-antibody-positive PBC in 2 woman with
CREST syndrome and in 1 woman with a acral-type of the progressive systemic
scleroderma. CREST syndrome and coexistently M2-antibodies in the serum are a
risk constellation for the development of PBC. In 2 female patients older than 50
years we observed the coincidence of disseminated plaque-like localized
scleroderma and a M2-antibody-positive PBC. In our opinion this latter
constellation is a specific entity. The administration of ursodeoxycholic acid
(daily 15 mg/kg BW) in 3 cases led not only to dramatic improvement of the
clinical symptoms of PBC as expected, but also to pronounced improvement of skin
lesions of 2 patients with disseminated circumscribed and 1 patient with
progressive systemic sclerosis. Thus PBC should be searched for in patients with
scleroderma, especially those with CREST syndrome or widespread localized
disease; it may have practical therapeutic value as well as immunological
significance.
PMID- 9642557
TI - [Laser skin resurfacing. Er:YAG laser and cw-CO2 laser with scanner system in
direct comparison].
AB - We compared a cw carbon dioxide flash-scanning laser system to an Er:YAG laser in
laser skin resurfacing of facial rhytides. In all patients, CO2 laser treatment
showed a better cosmetic result whereas erythema and postinflammatory
hyperpigmentation were less marked in Er:YAG laser therapy.
PMID- 9642558
TI - [Quality of life in chronic venous insufficiency (CVI). Results of a study with
the newly developed Tubingen Questionnaire for measuring quality of life of
patients with chronic venous insufficiency].
AB - Across the boundaries of the medical specialties we have realized how important
the concepts of quality of life and disease-related coping behavior are to
understand the patients' subjective perception of the medical condition and its
treatment. Although standardized instruments are already available for different
medical indications and even in the related fields of peripheral vascular and
cardiac diseases, phlebology still lacks standardized concepts for evaluating
quality of life and/or disease-related coping behavior in patients with chronic
venous insufficiency (CVI). We report on a newly developed instrument
specifically designed for recording quality of life in patients with CVI. It not
only meets the requirements of psychometric standards, but has also proven its
applicability in clinical use. The "Tubingen Questionnaire for measuring Quality
of Life in patients with CVI (TLQ-CVI)" and the results of a study on quality of
life in 142 patients with various stages of chronic venous insufficiency are
presented. It was possible to distinguish between Stage I/II and Stage III CVI
patients with respect to parameters such as "leg complaints" and "day-to-day
fears and worries". These convey clinically relevant insights into the patient's
subjective perception of the disease and how they cope. The information gathered
provides a set of reasonable target scores for clinical studies presently being
carried out at various study centers in Germany incorporating the TLQ-CVI.
PMID- 9642559
TI - [Incidence of gynecomastia in dermatology patients].
AB - Gynecomastia is an enlargement of the male breast. We studied a group of 115 men
attending a dermatological clinic to evaluate the frequency of possible risk
factors and hormonal findings. Gynecomastia was diagnosed, if a horizontal
skinfold exceeded 2-3 cm, and if the diameter of the areola wa greater than 3 cm.
In 32 patients (27.8%) the criteria for gynecomastia were fulfilled. The
frequency increased significantly with the body mass index. 18 different
medications were identified, but only two were take by more than two patients
(allopurinol, coronary dilators). None of the 15 underlying diseases was
associated with a significant increase or decrease in the risk of gynecomastia.
Serum cortisol was the only endocrine study which was associated with an
increased incidence of gynecomastia. As gynecomastia appears frequently as a
phenomenon unrelated to other diseases or medications, it may be a condition per
se.
PMID- 9642560
TI - [Lichen planopilaris simulating postmenopausal frontal fibrosing alopecia
(Kossard)].
AB - A 68-year old woman presented with a frontal fibrosing alopecia and lesions of
the buccal mucous membranes typical for lichen planus. Postmenopausal frontal
fibrosing alopecia (PFFA) has recently been described by Kossard as a distinct
entity characterized by progressive recession of the frontotemporal and parietal
hair margins leading to permanent alopecia in the form of a symmetrical band-like
area of scanning in postmenopausal women. The histology (perifollicular
lymphocytic infiltration and fibrosis, increase of apoptosis of hair follicle
keratinocytes) is indistinguishable from that of lichen planopilaris. The
localization and age- and sex-related characteristics of PFFA are not sufficient
to delineate it as a discrete entity from lichen planopilaris. Our observation of
oral lichen planus in a postmenopausal woman with frontal fibrosing alopecia
points to the possibility that PFFA actually may represent a variant of lichen
planopilaris with a predilection for the frontotemporal hairline. Other variants
of lichen planopilaris include multifocal lichen planopilaris, disseminated
lichen planopilaris (Lassueur-Graham-Little syndrome), lichenoid pseudopelade,
and any combination of these ("mixed type"). An effective therapy of PFFA is not
known. Also, treatment of lichen planopilaris forms in which fibrosis
predominates over inflammation is similarly problematic, but the natural course
of these diseases seems to be self-limited.
PMID- 9642561
TI - [Cutaneous sinus histiocytosis (Rosai-Dorfman disease)].
AB - Sinus histiocytosis is as a rule a benign disease of lymph nodes, infiltrated by
large histiocytes. These cells show typical cytophagocytosis, particularly
lymphophagocytosis. Other organs may be also involved by this disease, often
including the skin. Exclusive cutaneous sinus histiocytosis without infiltration
of lymph nodes seems to be very rare. To exclude other non-X histiocytoses or
histiocytosis-X, it is advisable to use immunohistochemistry. We report on a
patient with sinus histiocytosis and discuss the problems of differential
diagnosis.
PMID- 9642562
TI - [Tinea caused by Trichophyton equinum].
AB - We report on the first human infection with Trichophyton equinum in Germany,
which was transmitted from an infected pony to a 12-year old girl. Trichophyton
equinum was identified by its morphology, dependency on nicotinic acid, hair
perforation, and enzyme production. A noteworthy new observation was the
development of white pleomorphic tufts on the surface of thalli grown on potatoe
dextrose agar. The girl's tinea was non-inflammatory and responded promptly to
topical treatment, whereas the pony's strongly inflammatory lesions persisted for
months. In supernatants of cultures supplemented with different nutrients, enzyme
patterns were measured for Trichophyton equinum that correspond to other species
of dermatophytes more pathogenic for humans. Therefore, a lack of enzymes is
apparently not the explanation for the rarity of human infections with
Trichophyton equinum. More likely, predisposing factors of the host are necessary
in combination with a close contact to infected horses. Treatment of infected
humans appears to be no major problem.
PMID- 9642563
TI - [ANCA-positive lupus erythematodes profundus. Successful therapy with low dosage
dapsone].
AB - A 44-year-old male patient with lupus erythematosus profundus (lupus
panniculitis) (LEP) of the right cheek/infraorbital region presented as a
recurrent swelling. He had only anti-neutrophil-cytoplasmic antibodies (ANCA),
which have not been previously described in association with LEP. There was no
indication of systemic lupus erythematosus. While chloroquine produced no
benefits, the skin lesions promptly cleared with dapsone. Step by step we reduced
dapsone to a final dose of 50-75 mg per week. The ANCA titer decreased in
parallel to the clinical improvement.
PMID- 9642564
TI - [Linear and whorled nevoid hypermelanosis. Case report and review of the
literature].
AB - A 7 year old boy presented with linear and whorled nevoid hypermelanosis (LWNH).
This entity, delineated in 1988, is characterized by streaked or whorled,
frequently reticulate hyperpigmented lesions following the lines of Blaschko
without preceding inflammation and without atrophy. The age of onset is usually
within the first 2 years of life. Histologically, there is a mild basal cell
hyperpigmentation with prominent melanocytes. In contrast to earlier reports, we
observed some melanophages in the upper dermis. Associated abnormalities have
been reported in a few patients, but were absent in our case. We present the
clinical features, diagnostic criteria and differential diagnosis of this rare
entity. Apparently, our patient represents the first case of LWNH in the German
literature.
PMID- 9642565
TI - [From the "knight stronghold" into the 21st century. Chronology of the
dermatology department of the Spandau Hospital].
PMID- 9642566
TI - [MELISA--in vitro test for detection of contact allergy? A comment by the German
Contact Allergy Group].
PMID- 9642567
TI - [What is the relevance of "individual cases" for the legislator--here with
reference to the new communicable disease control law?].
PMID- 9642568
TI - [Tropical dermatology, travel medicine, vaccination. I].
PMID- 9642569
TI - To eat or not to eat: affective and physiological mechanisms in the stress-eating
relationship.
AB - The current study aggregated methods from the cardiovascular reactivity and
dietary restraint paradigms in an attempt to advance our understanding of stress
induced eating behavior. Seventy-seven female subjects completed a protocol
consisting of distinct baseline, stress-induction, and recovery phases during
which we monitored blood pressure, heart rate, and self-reported affect. Food was
inconspicuously made available to participants during the recovery phase. Our
results replicated the restraint x affect level interaction observed in the
restraint literature, while showing that physiological measures could further
explain distressed eating behavior. Physiological arousal was found reliably to
predict reduced food consumption, but only among unrestrained eaters. Analysis of
the recovery data showed that food consumption was associated with impaired
physiological recovery rates for restrained but not for unrestrained
participants. We believe that our results help to reconcile findings in the
stress, eating, and dietary restraint fields and offer support for recently
developed theories of stress-induced overeating.
PMID- 9642570
TI - Measuring stage of change for fruit and vegetable consumption in 9- to 12-year
old girls.
AB - This paper presents results of the pilot-testing of a stage of change measure for
eating fruit and vegetables (F & V) in 9- to 12-year-old girls. During troop
meetings, 259 girls from 22 troops completed a 1-day food recognition form, a
brief stage of change algorithm for fruit and for vegetables, and a questionnaire
measuring psychosocial variables associated with F & V consumption. Stages for F
& V consumption were different and MANOVAs revealed overall significant
differences across stages for each variable. F & V intake increased with higher
stages, as did preferences, self-efficacy for selecting, preparing, and eating F
& V, subjective norms, and F & V preparation skills; reported barriers decreased.
Stepwise discriminant analyses between Precontemplation and Contemplation stages
identified fruit preferences and barriers differentiating the two stages for
fruit consumption and subjective norms and self-efficacy differentiating the two
stages for vegetable consumption. Barriers and F & V preparation
responsibilities/skills were significant between the Contemplation and the Action
stages for both fruit and vegetable consumption, with the additional variable of
subjective norms for fruit stage and vegetable preferences for vegetable stage.
Findings support the use of this measure to identify stage for children's
adoption of F & V consumption behavior and as a guide for intervention
development.
PMID- 9642571
TI - Claustrophobia and the magnetic resonance imaging procedure.
AB - We examined fear induced by the magnetic resonance imaging (MRI) procedure in 80
adult patients who were undergoing the procedure for the first time. Participants
completed self-report measures of claustrophobia, anxiety sensitivity, thoughts
about the scan, and pain. Participants were assessed pre- and postscan, and at 1
month follow-up. Twenty-five percent of the participants experienced moderate to
severe anxiety during the MRI scan. Prescan scores on the Claustrophobia
Questionnaire (CLQ: Rachman and Taylor, 1993) significantly predicted
participants' distress during the scan: pain and anxeity sensitivity did not.
Furthermore, CLQ scores discriminated between participants who reported panic
during the scan and participants who did not report panic. A brief screening
instrument consisting of six items from the 29-item CLQ is suggested. This brief
screening instrument administered prior to the scan may help identify in advance
those people who are most likely to experience claustrophobic fear and, in
particular, those who panic during the MRI procedure.
PMID- 9642572
TI - Doctors, patients, and perceived job image: an empirical study of stress and
nurses in Singapore.
AB - This study examined the relationships among three potential sources of stress,
namely, demands from patients/relatives, demands from doctors, and perceived job
image, and several work-related outcomes, namely, job satisfaction,
organizational commitment, intention to quit, and job-induced tension.
Respondents consist of nurses from two tertiary-care hospitals in Singapore.
Findings of this study suggest that demands from patients/relatives, doctors, and
perceived job image were significantly associated with nurses' job satisfaction,
organizational commitment and job-induced tension. While demands from
patients/relatives and perceived job image were significantly associated with
intention to quit, the relationship between demands from doctors and nurses'
intention to quit failed to reach statistical significance. Implications of the
findings are discussed.
PMID- 9642573
TI - Patients' expectations of outcome of hysterectomy and alternative treatments for
menstrual problems.
AB - Patients can influence treatment to the extent of securing surgery in the absence
of medical need, but their expectations of effects of surgery are poorly
understood. Interviews with 26 patients presenting menstrual problems without
confirmed pathology were used to construct a questionnaire to measure
expectations of effects of treatment. Principal-components analysis of responses
of 200 similar patients identified six discrete areas in which improvement was
expected, including general well-being, menstrual function, and physical
symptoms. Expectations of harm were nonspecific and unidimensional. Component
based scale scores showed that patients who anticipated hysterectomy expected
more benefit, but also more harm, than those anticipating conservative
procedures. In study 2, these different expectations were largely replicated in
patients who were randomly allocated to provide their expectations of specific
procedures. Patients' uniquely positive expectations of hysterectomy may help to
explain its frequent use in the absence of pathology.
PMID- 9642574
TI - Examination of cognitive variables relevant to sunbathing.
AB - This study examined cognitions relevant to sunbathing decision-making in college
aged subjects. Using Jaccard's (1981) theory of alternative behavior as a guiding
model, 263 subjects were recruited from psychology classes and administered
questionnaires assessing their sunbathing behavioural tendencies, attitudes
toward sunbathing, attitudes toward reasonable behavioral alternatives to
sunbathing, and cognitive variables underlying these attitudinal variables. The
fits of models predicting sunbathing attitudes and sunbathing behavioural
tendencies (evaluated using covariate structural equations modeling techniques;
LIS-REL VIII) were good for all models tested. In contrast to previous work, the
results of this study support the notion that young people will make their
decisions regarding sunbathing based on the behavioral alternatives available to
them (i.e., generally the one that they prefer most). Furthermore, the
multivariate approach used clearly delineates the specific cognitive beliefs and
orientations that might be targeted to change these attitudes. The relevance of
these findings to skin cancer prevention interventions is discussed.
PMID- 9642575
TI - Preventing, diagnosing, and treating endophthalmitis.
PMID- 9642576
TI - Revising a myth.
PMID- 9642577
TI - Cataract surgery training of residents in an urban and virtual environment.
PMID- 9642578
TI - Inadvertent use of chlorhexidine as intraocular irrigation solution.
PMID- 9642579
TI - Consultation section. Cataract surgical problem.
PMID- 9642580
TI - Price graft-over-host technique to manage positive pressure during penetrating
keratoplasty.
AB - Intraoperative positive pressure with resulting iris and lens prolapse can pose a
difficult scenario during penetrating keratoplasty. In the Price graft-over-host
technique, the graft is sutured across the trephinated host cornea, which
maintains a formed anterior chamber and thus avoids intraoperative complications.
The technique was used in 33 eyes, and no primary or secondary graft failures
occurred. Eleven episodes of acute rejection in 11 eyes were treated successfully
with steroids.
PMID- 9642581
TI - Intracapsular foldable posterior chamber lens implantation in eyes with posterior
capsule tears or zonular fiber instability.
AB - A surgical technique is described for foldable posterior chamber intraocular lens
implantation in the capsular bag in the presence of a posterior capsule tear or
weakened zonular fiber support. Haptics are compressed by suturing before
endocapsular insertion, minimizing capsular and zonular fiber stress.
PMID- 9642582
TI - Comparative study of the elevation topography of complex shapes.
AB - PURPOSE: To compare the accuracy and precision of the elevation topography from
two commercially available instruments using videokeratoscopy or
rasterstereography. SETTING: University of Ottawa Eye Institute, Ottawa General
Hospital, Ontario, Canada. METHODS: Repeated measurements of elevation topography
of six calibrated surfaces were done with the PAR Corneal Topography System (CTS)
and the Tomey Topographic Modeling System (TMS-1). The shapes simulated normal
(A: aspheric, B: spherocylindric) and postsurgical corneas (C: hyperopic, D:
myopic, E: central island, F: phototherapeutic keratectomy). Surface shapes were
described by parametric equations. Equation parameters associated with each
elevation measurement were determined by best-fit analysis. Measurement precision
was assessed by the standard deviation of the difference between the fitted and
the measured data. Fitted parameters were compared with nominal values obtained
from an independent calibration of each surface. The root mean square error
(RMSE) of the deviation of the fitted from the nominal surfaces was used to
evaluate the accuracy of each instrument. RESULTS: The accuracy of the CTS
exceeded that of the TMS-1 for all surfaces measured. The RMSE values (micron)
were (A: 0.1, 6.5), (B: 0.3, 3.8), (C: 1.1, 11.8), (D: 5.0, 43.0), (E: 1.2, 3.2)
and (F: 2.2, 17.5) for the CTS and TMS-1, respectively. The differences in the
measured data from the fit surface were generally smaller with the TMS-1.
CONCLUSION: Quantitative analysis of elevation measurements showed that the CTS
represented surface topography more accurately than the TMS-1.
PMID- 9642583
TI - Noncontact holmium:YAG laser thermal keratoplasty for hyperopia.
AB - PURPOSE: To describe our experience with noncontact holmium:YAG laser thermal
keratoplasty (Ho:YAG LTK). SETTING: Refractive Surgery and Cornea Department,
Clinica de Ojos Dr. Nano, Buenos Aires, Argentina. METHODS: In this retrospective
study, 182 hyperopic eyes from 116 patients were treated with noncontact Ho:YAG
LTK. Mean age was 50 years +/- 7 (SD), and the spherical equivalent (SE) of the
subjective mean refraction (SMR) was +2.50 +/- 0.87 diopters (D). Eyes with
corneal power of more than 45 D, corneal pachymetry thicker than 550 microns, and
previous corneal surgery or disease were excluded. Holmium:YAG laser parameters
include one to three rings of eight spots arranged in a radial and symmetrical
array. Pulse energy was 240 mJ, with five pulses per spot. Patients were followed
for 12 months. RESULTS: The mean uncorrected visual acuity from 3 to 12 months
was 20/40 (20/200 to 20/25), improving an average of three Snellen lines. Mean
best spectacle-corrected visual acuity was 20/25 at all postoperative
examinations, the same as preoperatively. Mean SE of the SMR was +1.50 +/- 0.98 D
(range -0.75 to +4.50 D) at 6 months and +1.25 +/- 0.96 D (+0.25 to +3.25 D) at 1
year. After 9 months, 17% of operated eyes were retreated. CONCLUSION: In this
study, Ho:YAG LTK was safe and effective, provided satisfactory correction of low
hyperopia, and had a low complication rate. Good patient selection is the key to
obtaining good results.
PMID- 9642584
TI - Laser in situ keratomileusis for myopia and astigmatism: 6 month results.
AB - PURPOSE: To evaluate the visual and refractive results of laser in situ
keratomileusis (LASIK) for mild to moderate myopia with or without astigmatism.
SETTING: Barnet-Dulaney Eye Center, Phoenix, Arizona, USA. METHODS: Data were
prospectively collected on 124 consecutive eyes having LASIK over 12 weeks. Eyes
with a preoperative spherical equivalent (SE) from -1.35 to -10.00 diopters (D)
(mean -4.81 D +/- 2.21 [SD]) and cylinder from 0 to 5.00 D (mean 1.12 +/- 1.12 D)
were entered in the study. Thirty-one eyes had spherical corrections. Ninety
three eyes had spherocylinder corrections; preoperative astigmatism in these eyes
ranged from 0.50 to 5.00 D (mean 1.47 +/- 1.09 D). Surgery included creation of a
corneal flap using an automated microkeratome with a 160 microns plate followed
by photoablation on the exposed stromal bed. Photoablation was performed using
five zones varying from 5.0 to 6.6 mm in eyes with 6.25 D of myopia or less and
with five passes at a 5.0 mm zone in eyes with 6.50 D of myopia or more.
Astigmatism was corrected using a single-pass ablation through a 6.0 mm slit of
varying diameter. RESULTS: Six month follow-up was obtained in 89 eyes (72%). All
eyes were completely re-epithelialized by the first postoperative day.
Uncorrected visual acuity was 20/40 or better in 81% of eyes at 1 day and in 91%
at 6 months. At 6 months, the mean SE was -0.35 +/- 0.77 D; 83% were within +/-
1.00 D of plano. Postoperative astigmatism in the 93 eyes having cylinder
correction ranged from 0 to 1.22 D (mean 0.38 +/- 0.42 D). No eye lost more than
two lines of best spectacle-corrected visual acuity. Three eyes (2%) required
surgical intervention for cap problems. Visually significant corneal haze was not
observed. CONCLUSION: In eyes with myopia with or without astigmatism, LASIK
provided rapid visual recovery with satisfactory visual and refractive outcomes.
The effect of LASIK on visual function (night glare, contrast sensitivity) awaits
further study.
PMID- 9642585
TI - Astigmatic keratotomy effect of single-hinge, clear corneal incisions using
various preincision lengths.
AB - PURPOSE: To investigate the astigmatic keratotomy effect of a modified single
hinge cataract incision. SETTING: Department of Ophthalmology, San Juan de Dios
Hospital, Tenerife, Spain. METHODS: This prospective study evaluated the
astigmatic changes resulting from preincision grooves of less than 40, 45, and 55
degrees in arc length used with a single-hinge, self-sealing cataract incision in
144 eyes that had against-the-rule corneal astigmatism preoperatively. The
intended 90% depth preincision was centered on the steep meridian and lengthened
according to the amount of preoperative astigmatism. Outcome measurements were
obtained by calculating the surgically induced astigmatism vectors and the
postoperative keratometry changes 1 day, 1 week, and 1, 3, and 6 months after
surgery. RESULTS: Three months postoperatively, astigmatism decreased by 0.03,
0.30, and 0.68 diopter in the less than 40, 45, and 55 degree incision length
groups, respectively. The differences between the 45 and 55 degree groups and the
less than 40 degree group was statistically significant (P < .05). Similar
results were observed 6 months after surgery. CONCLUSION: The astigmatic
preincision modification produced statistically significant increasing reductions
in preoperative astigmatism according to preincision length.
PMID- 9642586
TI - Retinal detachment after cataract extraction in myopic eyes.
AB - PURPOSE: To determine the incidence of retinal detachment (RD) after cataract
extraction in people 40 years of age or older with axial myopia (i.e., axial
length > or = 25.5 mm). SETTING: Fifteen Danish eye clinics. METHODS: Two hundred
forty-five eyes had cataract extraction performed at 15 eye clinics; 237 eyes had
extracapsular cataract extraction (ECCE) and 8 eyes, intracapsular cataract
extraction (ICCE). Postoperative data were reported by the practicing
ophthalmologists. Mean follow-up was 27 months (range 14 to 32 months). RESULTS:
Five RDs occurred in the 245 eyes (2.0%). Excluding the ICCE cases and the two
cases of combined cornea transplantation and ECCE, RD occurred in 4 of the 235
eyes that had ECCE (1.7%). The incidence after ECCE with posterior chamber lens
implantation was 1.4%. Complete postoperative status was reported on 158 eyes.
Forty-eight eyes (30.4%) had a neodymium:YAG capsulotomy and 3 (6.0%) developed
an RD 1, 3.5, and 21 months after the capsulotomy. CONCLUSION: The RD incidence
after ECCE with posterior chamber lens implantation was low but higher than that
in unselected populations. The incidence increased after laser capsulotomy.
PMID- 9642587
TI - Retinal detachment following phacoemulsification in highly myopic cataract
patients.
AB - PURPOSE: To assess whether modern, small incision phacoemulsification techniques
significantly reduce the retinal detachment (RD) risk in highly myopic patients
who have visually significant cataracts. SETTING: University-associated
ophthalmology practice. METHODS: This retrospective study included 80 eyes in 61
patients with preoperative myopia of 7.00 diopters (D) or more. Sixty-four eyes
had an axial length of 25.0 mm or greater. All surgery was performed superiorly
using a frown-shaped, self-sealing, scleral tunnel. The incision size ranged from
3.0 to 5.0 mm. Capsulorhexis was performed and then four-quadrant cracking
phacoemulsification. The posterior capsule was routinely polished. A posterior
chamber intraocular lens (IOL) was implanted in the capsular bag in all cases.
RESULTS: No RDs occurred during the mean follow-up of 43 months (range 9 to 77
months) or the mean follow-up after neodymium:YAG capsulotomy of 20 months. No
intraoperative complications occurred. Seventy-one of 80 eyes (89%) achieved best
spectacle-corrected visual acuity of 20/25 or better. CONCLUSIONS: Retinal
detachments following modern cataract surgery in high myopia are much less common
than previously reported. We attribute this to small incision size, continued
maintenance of the anterior chamber, posterior chamber IOL implantation, and lack
of intraoperative complications.
PMID- 9642588
TI - Phacoemulsification, intraocular lens implantation, and trabeculotomy to treat
pseudoexfoliation syndrome.
AB - PURPOSES: To determine the long-term risk/benefit ratio of phacoemulsification
and intraocular lens (IOL) implantation combined with trabeculotomy to manage
eyes with pseudoexfoliation syndrome and co-existing cataract. SETTING:
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School
of Medicine; Kurihara Eye Clinic; Departments of Ophthalmology, Tenri Hospital,
Kumamoto University, and Matsue Red Hospital; Nagata Eye Clinic, Japan. METHODS:
This multicenter retrospective study comprised 49 eyes of 36 patients with
pseudoexfoliation syndrome and co-existing cataract who had the combined
procedure for uncontrolled intraocular pressure (IOP) (> 21 mm Hg) even on
antiglaucoma medication. RESULTS: After a mean follow-up of 20.0 months +/- 13.2
(SD), IOP in all 49 eyes was well controlled (< or = 21 mm Hg). Mean IOP at the
final examination was 14.6 +/- 2.6 mm Hg on a mean of 0.9 +/- 0.8 glaucoma
medications. Complications included an IOP spike in 11 eyes and fibrin exudation
in 1 eye. CONCLUSION: Phacoemulsification and IOL implantation combined with
trabeculotomy was an effective treatment for patients with pseudoexfoliation
syndrome and cataract.
PMID- 9642589
TI - Phacoemulsification in eyes with pseudoexfoliation.
AB - PURPOSE: To compare intraoperative and postoperative complications in eyes with
and without pseudoexfoliation having cataract surgery by phacoemulsification.
SETTING: Department of Ophthalmology, National Hospital, Oslo, Norway. METHODS:
Of 1152 consecutive phacoemulsification procedures, 164 cases with
pseudoexfoliation (Group 1) and 916 cases without (Group 2) were followed for 4
months after cataract surgery in a prospective study. Of all cataract operations
performed during that time, 96.2% were phacoemulsification procedures; 90.4 and
97.4% in eyes with and without pseudoexfoliation, respectively (P < .0005).
RESULTS: The frequency of capsular/zonular tear or vitreous loss was 9.6 and 3.7%
in Groups 1 and 2, respectively (P = .0002). A visual acuity of 0.5 or better was
achieved in 86.5% of eyes in Group 1 and 92.4% in Group 2 (P = .02). There were
no statistically significant between-group differences in the frequency of a
postoperative inflammatory response 1 day (6.7 versus 4.4%), 1 week (2.4 versus
1.6%), or 4 months (1.8 versus 0.9%) postoperatively. CONCLUSION:
Phacoemulsification was safe in most eyes with pseudoexfoliation even though
significantly more complications occurred intraoperatively in these eyes. The low
frequency of an inflammatory response indicates that the presence of
pseudoexfoliation does not significantly increase the risk of inflammation.
PMID- 9642590
TI - Risk of acute suprachoroidal hemorrhage with phacoemulsification.
AB - PURPOSE: To establish whether small incision cataract surgery with
phacoemulsification decreases the risk of acute suprachoroidal hemorrhage (ASCH)
compared with traditional nucleus expression by extracapsular cataract extraction
(ECCE). SETTING: St. Erik Eye Hospital, Stockholm, Sweden. METHODS: A
retrospective study was done on the incidence of ASCH in cataract surgery between
July 1990 and July 1996. During this period, 37,565 cataract extractions
(phacoemulsification and ECCE) were performed at St. Erik Eye Hospital, combined
procedures excluded. The criteria for diagnosis were the suspicion of ASCH during
surgery and a verified diagnosis via an expulsive hemorrhage into the wound (4
cases), postoperative ultrasonic examination (20 cases), or a choroidal mass on
performing ophthalmoscopy together with a postoperative history alluding to the
diagnosis (2 cases). RESULTS: Twenty-six eyes were identified with ASCH,
including 7 during phacoemulsification and 19 during ECCE. The incidence of ASCH
was 0.03% in the 23,213 phacoemulsification cases and 0.13% in the 14,352 ECCE
cases. The difference was statistically significant (P = .0003; chi-square test).
CONCLUSION: Small incision surgery with phacoemulsification decreased the risk of
ASCH in cataract surgery compared with the traditional nucleus expression
technique.
PMID- 9642591
TI - Vitreous loss during conversion from conventional extracapsular cataract
extraction to phacoemulsification.
AB - PURPOSE: To study the outcome of vitreous loss among senior surgeons converting
from conventional extracapsular cataract extraction (ECCE) to
phacoemulsification. SETTING: A university teaching hospital in the United
Kingdom. METHODS: A retrospective analysis of 87 planned cataract extractions
performed from January 1992 to December 1996 and complicated by vitreous loss was
done. Outcome measures included postoperative complication rates and visual
acuity. RESULTS: During the study, vitreous loss occurred in 39 patients having
ECCE and in 48 having phacoemulsification; the latter group included 8 patients
with dropped nucleus. Postoperative complications included cystoid macular edema
(18.7% of phaco patients, 30.8% of ECCE patients), retinal detachment (2.1% of
phaco patients, 5.1% of ECCE patients), and expulsive hemorrhage (5.1% of ECCE
patients). Phaco patients had higher rates of postoperative corneal edema (27.1%)
than ECCE patients (12.8%) and transient intraocular pressure elevation (33.3%)
versus 20.5%) but were more likely to receive posterior chamber intraocular
lenses (70.8% versus 35.9%; P = .0024, chi-square test). After excluding pre
existing diseases, 83.3% of phaco patients and 67.6% of ECCE patients achieved a
visual acuity of 6/12 or better. CONCLUSIONS: With careful patient selection,
experienced extracapsular surgeons converting to phacoemulsification can achieve
favorable results even in the presence of complications such as vitreous loss or
dropped nucleus.
PMID- 9642592
TI - Phacoemulsification cataract surgery in vitrectomized eyes.
AB - PURPOSE: To determine the problems, safety, and results of phacoemulsification
cataract surgery in previously vitrectomized eyes. SETTING: Department of
Ophthalmology of Galdacano Hospital, Galdacano, Spain. METHODS: In this
prospective study, phacoemulsification was performed in 23 eyes that had had
vitrectomy between February 1992 and May 1994. Surgical and postsurgical
difficulties and complications and visual acuity results were analyzed. Follow-up
ranged from 12 to 24 months. RESULTS: The incidence of surgical problems and
complications was higher than usual: 7 eyes presented small pupil size (< 3.0
mm); sudden changes in anterior chamber depth and pupil size during surgery
occurred in 6 eyes; unusual mobility and flaccidity of the posterior capsule was
observed in 6 cases, which was associated with posterior subcapsular cataract and
young age (< 50 years); posterior capsule tear occurred in 2 eyes, 1 of which
required anterior vitrectomy. Postoperatively, best visual acuity improved two
Snellen lines or more in 17 eyes (73.91%), did not change in 3 (13.04%), and
worsened in 3. CONCLUSION: Phacoemulsification in vitrectomized eyes presented
more problems and complications than usual. However, it seems to be safer than
manual extracapsular surgery because it minimized the risk of intraoperative eye
hypotony or collapse.
PMID- 9642593
TI - Anterior chamber metal fragments after phacoemulsification surgery.
AB - PURPOSE: To determine whether metal fragments can be shaken loose from phaco
needles during surgery and embed in the iris. SETTING: Private practice, Vernon,
British Columbia, Canada, and scanning electron microscope laboratory, Mastel
Precision, Rapid City, South Dakota, USA. METHODS: The surfaces and rims of new
and used phaco needles and the lumens of halved new needles were examined by
scanning electron microscopy (SEM). To determine whether the fragments on the
phaco needles were approximately the same size as those seen in the iris, a
photograph of an eye with metal fragments imbedded in the iris was projected and
the image size of the metal fragments approximated by using their magnification
value. The magnification scale of the SEM images was used to determine the size
of the metal fragments photographed on the phaco needles. RESULTS: The SEM
studies of new phaco needles revealed tiny fragments of metal firmly adherent to
the interior, exterior, and rim surfaces. No fragments were detected on the
surfaces of the used phaco needles. Two metal fragments in the eye photograph
were calculated to be 0.20 x 0.20 mm and 0.15 x 0.20 mm. Those in the SEM photos
were calculated to be 0.03 to 0.10 mm. CONCLUSION: Althogh SEM of new titanium
phaco needles revealed adherent metal fragments on their lathed surfaces, no
fragments were found on used phaco needles. The iris fragments calculated from a
projected photograph were slightly larger than those from the SEM micrographs,
supporting the conclusion that annealed metal fragments shook loose from the
phaco needles. This indicates that ultrasonic activation of a new phaco needle
with metal fragments annealed to its surface causes fragments to release and
embed in the iris.
PMID- 9642594
TI - Prospective, randomized trial comparing Micro Visc Plus and Healon GV in routine
phacoemulsification.
AB - PURPOSE: To compare the safety and efficacy of two sodium hyaluronate
viscoelastics--MicroVisc Plus and Healon GV--in routine phacoemulsification and
evaluate whether these more viscous and cohesive agents offer benefits compared
to viscoelastics of standard viscosity and cohesion. SETTING: York Finch Eye
Associates and York Finch General Hospital, Toronto, Canada. METHODS: An
unmasked, randomized, prospective clinical trial of 100 eyes of 100 patients
having routine phacoemulsification with intraocular lens implantation was
conducted comparing the safety and efficacy of MicroVisc Plus with those of
Healon GV. Preoperative and 6 hour, 1 and 5 days, and 1 and 6 month postoperative
assessments included acuity, corneal thickness, intraocular pressure, and surgeon
assessment of the task-facilitating efficacy of the viscoelastics. Results were
compared with those of a similar trial of MicroVisc and Healon. RESULTS: There
were no statistically significant differences between the two treatment groups at
any follow-up. The surgeon judged the two viscoelastics to be equivalent,
although somewhat different in facilitating surgery. There was significantly less
transient postoperative corneal thickening in the Healon GV/MicroVisc Plus group
than in the Healon/MicroVisc group. CONCLUSIONS: Healon GV and MicroVisc Plus
were safe and provided equal outcomes based on the parameters assessed. MicroVisc
Plus' higher zero-shear viscosity caused it to behave slightly differently than
Healon GV during surgery. More viscous, cohesive viscoelastics may increase
surgical safety.
PMID- 9642595
TI - Diagnosis of infectious endophthalmitis after cataract surgery by polymerase
chain reaction.
AB - PURPOSE: To ascertain whether the use of the polymerase chain reaction (PCR)
technique leads to more rapid diagnosis of infectious endophthalmitis after
cataract surgery. SETTING: University Eye Clinic Regensburg, Germany. METHODS:
The aqueous humor and vitreous of 16 eyes with infectious endophthalmitis (10
acute, 6 delayed) were evaluated by microscopy, diagnostic culture, and PCR to
detect the infectious agent. RESULTS: Microscopy of the vitreous was positive in
3 eyes and the culture media results were positive in 7 eyes, all with acute
endophthalmitis. Significantly fewer positive results were obtained in the
aqueous humor. Using PCR, an infectious agent was detected in the aqueous humor
of all 16 eyes and in the vitreous of 14. The vitreous sample was negative in 2
eyes with delayed endophthalmitis. CONCLUSIONS: Detection of the infectious agent
was more successful using PCR than using conventional microbiological tests,
especially in the diagnosis of delayed endophthalmitis where the pathogen was
detected in the aqueous humor in all eyes.
PMID- 9642596
TI - Detachment of Descemet's membrane.
AB - PURPOSE: To determine predisposing factors, best method of treatment, and the
final outcome in cases of Descemet's membrane detachment. SETTING: A tertiary
care teaching eye hospital. METHODS: All cases of Descemet's detachment from
January 1986 to May 1994 were retrospectively reviewed. Twelve eyes of 11
patients with partial or total detachment of Descemet's membrane were identified.
Patients with small localized detachments at the incision area were excluded.
RESULTS: All but one patient had surgical repair. Ten eyes had successful
reattachment after up to four attempts at repair. Methods of repair included
intracameral air or sulfur hexafluoride (SF6) 20% gas, with or without corneal
sutures. After a followup of 3 to 79 months, eight eyes retained clear corneas,
four eyes developed corneal edema and scarring, and two required penetrating
keratoplasty. No definite predisposing factor could be identified, although four
eyes had preoperative diagnoses of glaucoma and recent corneal edema. CONCLUSION:
Surgical repair with injection of intracameral air or SF6 20% was successful in
most cases of Descemet's membrane detachment. A preoperative diagnosis of
glaucoma and a recent episode of corneal edema may increase the risk of
detachment.
PMID- 9642597
TI - Analysis of preoperative factors predictive of visual acuity in axial myopia.
AB - PURPOSE: To identify the factors predicting visual acuity after cataract surgery
in patients with high myopia. SETTING: Departments of Ophthalmology, Showa
University School of Medicine and Showa University Fujigaoka Hospital, Kanagawa,
Japan. METHODS: Stepwise regression analysis was used to identify the factors
determining the visual acuity in 940 eyes with an axial length of 27.0 mm or
longer having cataract surgery. Using a formula derived from the stepwise
regression analysis, the predicted postoperative visual acuity was compared with
the actual value measured in another group of 104 eyes. RESULTS: Five factors
were identified to significantly determine postoperative visual acuity: axial
length, age, corneal opacity, refractive power of the cornea, and history of
retinal detachment surgery. There was a significant relationship between
predicted and actual postoperative visual acuities (r = .51, P < .001).
Postoperative visual acuity was similar in 63% of cases. CONCLUSION: The results
showed that at least five factors determine visual acuity after cataract surgery
in patients with high myopia.
PMID- 9642598
TI - Comparison of ciliary sulcus fixation techniques for posterior chamber
intraocular lenses.
AB - OBJECTIVE: To anatomically and histologically evaluate suturing techniques for
sulcus fixation of posterior chamber intraocular lenses. SETTING: Kitano
Hospital, Osaka, Japan. METHODS: The reproducibility of three suturing techniques
(perpendicular to the eye wall; parallel to the iris; midway between
perpendicular to the eye wall and parallel to the iris) were evaluated in a
postmortem eye. Histologic sections of another eye and ultrasound biomicroscopy
(UBM) images of 21 normal eyes were evaluated to determine the safety zone for
the needle to avoid damaging adjacent structures. RESULTS: The ciliary sulcus was
completely penetrated in the three techniques in 100, 40, and 70% of cases,
respectively. The histologic sections and the UBM images showed that when sutures
were placed perpendicular to the eye wall, there was the possibility of
postoperative angle closure and suturing parallel to the iris might damage
adjacent structures because of a narrow safety zone. CONCLUSIONS: The needle
should penetrate obliquely, as in the technique in which the suturing is midway
between perpendicular to the eye wall and parallel to the iris. This technique
provides better reproducibility and causes less damage to adjacent tissue.
PMID- 9642599
TI - Outcomes and ocular growth rates after intraocular lens implantation in the first
2 years of life.
AB - PURPOSE: To evaluate the outcomes and ocular growth after intraocular lens (IOL)
implantation in the first 2 years of life. SETTING: University-affiliated eye
institute. METHODS: The medical records of consecutive children under 24 months
of age who had cataract extraction with IOL implantation were reviewed. Change in
axial length over time, postoperative complications, need for additional surgery,
predicted versus actual postoperative refraction, and visual outcomes were
recorded. Complication rates were compared with those in a similar group of age
matched patients who were left aphakic at the time of surgery. RESULTS: Twenty
two eyes of 17 patients aged 12 days to 22 months had IOL implantation. Length of
follow-up ranged from 2 to 36 months (mean 14 months). Visual acuity measurement,
limited to fixation-preference testing in most patients, revealed amblyopia in
the operated eye in the majority of cases. Postoperative refractive error,
predicted using the Holladay formula, showed a mean error in prediction of 1.5
diopters (D) (range -1.8 to 4.1 D). Serial axial lengths in 11 patients with a
mean follow-up of 20 months showed no significant difference in growth in the
fellow versus the operated eye. There was no significant difference in
complication rates between pseudophakic patients and the age-matched aphakic
group. However, in 14 of 32 aphakic eyes (44%), a notation in the chart indicated
that the patient had stopped wearing glasses or contact lenses for at least 2
months. CONCLUSION: Intraocular lens implantation appeared to be a safe and
effective alternative to contact lens or spectacle correction of aphakia in
children younger than 2 years of age. It may aid amblyopia treatment by
eliminating periods of uncorrected aphakia.
PMID- 9642600
TI - Prospective evaluation of topical versus retrobulbar anesthesia: a converting
surgeon's experience.
AB - PURPOSE: To evaluate and compare the efficacy of topical versus retrobulbar
anesthesia for cataract surgery performed by a surgeon newly converting to the
topical technique. SETTING: Department of Ophthalmology, Moran Eye Center,
University of Utah, Salt Lake City, Utah, USA. METHODS: Ninety patients were
prospectively assigned by permuted block restricted randomization to receive
topical (Group 1; n = 45) or retrobulbar (Group 2; n = 45) anesthesia. Group 1
received topical bupivacaine 0.75% and intravenous midazolam and fentanyl for
anesthesia. Group 2 received intravenous methohexital followed by retrobulbar
block with an equal mixture of lidocaine 2% and bupivacaine 0.75% plus
hyaluronidase 150 units. A visual pain analog scale was used to assess the degree
of pain during anesthesia administration and surgery and postoperatively. The
degree to which eye movement, touch, and light caused patient discomfort was
assessed. Intraoperative conditions and complications were recorded. RESULTS:
Intraoperative operating conditions were significantly better in Group 2 (P <
.05). There was a small but statistically significant difference in the degree of
discomfort during anesthesia administration and surgery (P < .05). There was no
difference in postoperative discomfort. Chemosis, subconjunctival hemorrhage, and
eyelid hemorrhage occurred only in Group 2, in which there was one retrobulbar
hemorrhage. Although eyelid squeezing and ocular motility were present more
frequently in Group 1, neither was a problem to the surgeon. CONCLUSION: Cataract
surgery was safely performed by a surgeon converting to topical anesthesia. After
a distinct learning curve, the procedure was performed with minimal patient
discomfort. Surgical training and patient preparation are the key to safe use of
topical anesthesia.
PMID- 9642601
TI - Paradoxical response to photorefractive treatment for postkeratoplasty
astigmatism.
AB - A 42-year-old woman with functionally disabling postkeratoplasty astigmatism in
her right eye 3 years after corneal transplantation for keratoconus received
photorefractive keratectomy for high astigmatism in that eye. This did not reduce
her astigmatism. The procedure was repeated and corneal astigmatism paradoxically
increased. The forces within the pseudo-optical ring that cause and maintain
astigmatism in corneal transplants may be a significant factor in the
unpredictable response of some corneal transplants to excimer photorefractive
astigmatism correction.
PMID- 9642602
TI - Delayed-onset Pseudomonas stutzeri endophthalmitis after uncomplicated cataract
surgery.
AB - An 88-year-old woman had uneventful extracapsular cataract extraction with
posterior chamber intraocular lens (IOL) implantation in her right eye. Seven
weeks later, an anterior vitrectomy with removal of the IOL was performed because
of endophthalmitis resistant to topical and systemic amoxicillin, cephalosporin,
aminoglycoside, and steroids. Microbiological examination of the vitreous biopsy,
capsule, and anterior chamber fluid disclosed Pseudomonas stutzeri, gram-negative
nonfermentative bacteria sensitive to tetracycline, ceftazidime, gentamicin,
ofloxacin, and piperacillin. Pseudomonas stutzeri should be considered in the
treatment of delayed-onset endophthalmitis.
PMID- 9642603
TI - Traumatic cataract with a ruptured posterior capsule from a nonpenetrating ocular
injury.
AB - An 11-year-old boy had posterior lens capsule rupture resulting from a
nonpenetrating (blunt trauma) injury to the eye. A rapidly developing cataract
required pars plana lensectomy. This report suggests that posterior capsule
rupture may occur secondary to blunt trauma and progressive cataract formation
after posterior capsule rupture may require surgery soon after the injury.
PMID- 9642604
TI - Anterior capsulotomy created by radiofrequency endodiathermy and continuous
curvilinear posterior capsulorhexis in a patient with intumescent cataract and
primary capsular fibrosis.
AB - A 62-year-old woman with intumescent cataract and primary posterior capsular
fibrosis was operated on using two different techniques to create continuous
curvilinear capsule openings in the same eye. The biomicroscopic appearance of
the edge after continuous tear and radiofrequency endodiathermy capsulotomy were
compared.
PMID- 9642605
TI - Antibiotic treatment in preterm labor and intact membranes: a randomized, double
blinded, placebo-controlled trial.
AB - Although an association between microbial invasion of amniotic cavity and preterm
birth has been extensively demonstrated, there is conflicting evidence regarding
the benefits of antibiotic therapy in patients with preterm labor and intact
membranes. We attempted to assess the efficacy of amoxicillin and erythromycin on
pregnancy outcome in those patients. A randomized, double-blinded, placebo
controlled trial was designed and implemented. A total of 196 patients with
singleton pregnancies and preterm labor with intact membranes (22-36 weeks) were
randomly allocated to receive either antibiotics or placebo, plus adjunctive
parenteral tocolysis, and 173 patients (antibiotics group n = 83 vs. placebo
group n = 90) completed the treatment. The overall prevalence of microbial
invasion of the amniotic cavity was 5.2% (9/173). No significant difference
between both groups was found in maternal outcomes, including duration of
randomization-to-delivery interval, frequency of preterm delivery, and frequency
of clinical chorioamnionitis and endometritis. Rate of cesarean section was
significantly higher in the placebo group (28% vs. 12%). Regarding neonatal
outcome, no significant difference was detected between both groups in neonatal
death, respiratory distress syndrome, proven sepsis, and birthweight. Suspected
sepsis was significantly more frequent in the placebo group (6/90 vs. 0/78). The
results of this trial indicate that amoxicillin and erythromycin do not prolong
pregnancy in patients with preterm labor and intact membranes. A significant
reduction in the rate of cesarean section was observed in patients receiving
antibiotics. A significant reduction in the rate of neonatal suspected sepsis was
also demonstrated.
PMID- 9642606
TI - New triple screen test for Down syndrome: combined urine analytes and serum AFP.
AB - In this study we report a new triple test that combines serum AFP, urine beta
core fragment of hCG, total urine estriol, and maternal age for calculating
individual Down syndrome odds in the second trimester. The urine beta-core
fragment/estriol ratio was used as a single screening variable. Analyte levels
were measured prospectively in 10 Down syndrome cases and 346 normals. Individual
Down syndrome odds were calculated by multiplying the product of the Down
syndrome likelihood ratios of serum AFP and urine beta-core/estriol levels by the
age-related midtrimester risk. The screening efficiency of an algorithm that
combines urine beta-core/estriol with maternal age was compared to one that
included serum AFP data. A 90% detection rate for Down syndrome was obtained at a
4.65% false positive rate. This was superior to the 75% sensitivity at 5% false
positive rate observed when beta-core/estriol and age alone were used. This new
triple test has a higher screening efficiency than that generally reported for
the traditional serum triple screen and other urine tests, and it also provides
information on the risk of neural tube defects. If confirmed in larger trials,
the new algorithm could be used as an alternative to the traditional serum triple
screen.
PMID- 9642607
TI - Efficacy of intravaginal misoprostol in second-trimester pregnancy termination: a
randomized controlled trial.
AB - A prospective randomized, double-blind, controlled clinical trial to compare the
clinical efficacy and side effects of intravaginal misoprostol with the
traditional prostaglandin, gemeprost, in second-trimester pregnancy interruption
was conducted. A sample size of 100 women was calculated to demonstrate that
misoprostol was as effective as gemeprost in achieving delivery within 24 hours
(alpha = 0.1, 80% power). Women were recruited with fetal death in utero, severe
fetal anomaly, or psychosocial pregnancy termination between 14 and 28 weeks
gestation and randomized to receive either 1 mg gemeprost 3 hourly for 5 doses,
or 200 mcg misoprostol 6 hourly for 4 doses, intravaginally. The therapeutic
regimens were repeated if undelivered by 24 hours. Those undelivered after 48
hours received an extra-amniotic PGF2 alpha infusion. The median gestation at
recruitment was identical: gemeprost 19 weeks (IQ 17-22 weeks) vs. misoprostol 19
weeks (IQ 17-21 weeks), P = 0.887. Delivery within 24 hours occurred in 75.1% of
women receiving gemeprost and 74.9% receiving misoprostol (P = 1.0). The median
time from prostaglandin commencement to delivery was similar: gemeprost 13.7
hours (IQ 9.0-23.5 hours) vs. misoprostol 16.9 hours (IQ 10.3-23.5 hours), P =
0.769. A significant reduction in the incidence of vomiting in women randomized
to misoprostol occurred (34% vs. 13.2%, P = 0.017). There was no significant
difference in the incidence of maternal fever > 37.5 degrees C, nausea, diarrhea,
or placental retention. A 200-fold pharmaceutical cost advantage was observed
with the use of misoprostol compared with gemeprost. Intravaginal misoprostol
performs as effectively as gemeprost in achieving delivery in the second
trimester without increase in adverse effects and displaying a significant cost
advantage.
PMID- 9642608
TI - Superior mesenteric artery flow velocity waveforms in small for gestational age
fetuses.
AB - The objective of this study was to analyze the superior mesenteric artery flow
velocity waveforms in small-for-gestational-age fetuses and to compare its
contribution in their management with that already provided by the middle
cerebral artery and umbilical artery flow velocity waveforms. Middle cerebral
artery, umbilical artery, and superior mesenteric artery flow velocity waveforms
were prospectively obtained in 41 small-for-gestational-age fetuses with color
Doppler ultrasonography. The pulsatility index was used to quantify the
waveforms. Poor perinatal outcome was defined by cesarean section for fetal
distress, perinatal death, need for assisted ventilation, and necrotizing
enterocolitis. In the small-for-gestational age fetuses, the middle cerebral
artery pulsatility index was abnormal in 22/41, the umbilical artery in 26/41,
and the superior mesenteric artery in 17/41. Coincident with abnormal umbilical
and middle cerebral artery flow velocity waveforms were greater occurrences of
poor perinatal outcome. The abnormality of an increased pulsatility index in the
superior mesenteric artery velocity waveforms of small-for-gestational-age
fetuses suggests greater vascular resistance and an overall reduction in visceral
perfusion. However, the study of the superior mesenteric artery only seemed to
support the information already provided for by the middle cerebral and umbilical
arteries.
PMID- 9642609
TI - Statistical models of outcome in malpractice lawsuits involving death or
neurologically impaired infants.
AB - The objective was to determine whether factors could be identified in medical and
legal records that are associated with the successful defense of obstetrical
malpractice cases involving the death or neurological impairment of infants.
Obstetrical claims (169) closed by PROMUTUAL between January 1, 1990, and
December 31, 1994, were retrospectively abstracted and analyzed to identify
associations between medical and legal factors, and the medicolegal outcome.
Multivariable analysis identifies that the use of pitocin, diagnosis of asphyxia,
a delay in delivery, and the use of multiple defense expert witnesses decreased
the chances of a successful defense. Two statistical models explaining indemnity
payment were developed. The first, based on medical outcome, showed an increased
indemnity payment when a case involved major neurological deficits, diagnosis of
asphyxia, newborn seizures, later year of delivery, and participation of a
particular defense firm. Perinatal or childhood death and the use of pitocin were
indicators of a decrease in payment. The second model was based on long-term care
requirements. In this model, indicators of increased indemnity payment were:
nonreassuring intrapartum fetal heart rate tracing, later year of delivery,
intensity of long-term care required, and participation of a particular defense
law firm. Perinatal or childhood death, the use of pitocin, and settlement date
increasingly removed from the occurrence date were the determinants of decreased
payments in this model. Finally, the presence of major neurological deficits, the
prolongation of a case, and the involvement of multiple law firms and defense
witnesses increased the expense charged to and paid by the insurance company.
Using the medical, legal, and financial data relevant to 169 obstetrical cases
closed by one malpractice insurance carrier between 1990 and 1994, statistical
models with potential predictive values for future malpractice claims involving
neurologically impaired infants were constructed. These models may help determine
in advance the chance a future case has for successful defense and the likely
amount of expense and indemnity dollars that will be paid out to settle and
defend it.
PMID- 9642610
TI - Subgaleal hemorrhage in a premature infant with congenital diaphragmatic hernia
following vacuum-assisted delivery.
AB - An infant with congenital diaphragmatic hernia was delivered by vacuum
extraction, with a resultant subgaleal hemorrhage that excluded him from ECMO.
The literature regarding vacuum-assisted delivery and birth trauma is reviewed in
the context of congenital anomalies that may require ECMO support, and
recommendations for perinatal management are suggested.
PMID- 9642611
TI - Variation in use of corticosteroids among infants < or = 1,500 grams across
hospitals in three states.
AB - We identified factors associated with no antenatal corticosteroid treatment among
1,369 women who delivered infants < or = 1,500 g and < 34 weeks gestation, 1991
1993. At four hospitals, infants weighing 500-1,500 g were enrolled. Information
regarding corticosteroid use, maternal characteristics, and perinatal events were
obtained. Factors associated with no corticosteroid treatment were examined in
unadjusted and adjusted logistic regression models. Overall, 693 (50.6%) women
did not receive corticosteroids. Two hospitals had higher rates of no
corticosteroid usage (89% and 75%) as compared with the other two (32% and 50%).
Black, Hispanic, and poor women were more likely to receive care at the hospitals
where the rates of corticosteroid utilization were lower. Factors in the
multivariate model included: < 1 or 1 day of hospitalization, vs. delivery on >
or = 2 days of hospitalization (21.4: 14.5, 97.2; 4.7: 3.2, 6.9); gestational age
< 26 weeks (2.7: 1.8, 4.1) or > 28 weeks (1.8: 1.3, 2.6) vs. 26-28 weeks; < 12
hours of labor vs. > 12 hours (1.7: 1.2, 2.4); delivering at hospital 2, 3, 4 vs.
hospital 1 (1.6: 1.1, 2.5; 24.3: 13.6, 43.4; 10.2: 6.8, 15.3). We conclude that
variations in hospital practice limit widespread use of this important antenatal
treatment.
PMID- 9642612
TI - Does labetalol predispose to pulmonary edema in severe pregnancy-induced
hypertensive disease?
AB - We investigated whether use of labetalol, a beta adrenoreceptor blocking
antihypertensive agent commonly employed as an alternative to hydralazine, is
independently associated with pulmonary edema in women with severe preeclampsia.
We retrospectively evaluated women with severe preeclampsia who were given
labetalol by intravenous bolus for MAP > 120 mm Hg. Outcome variables included:
achieving MAP < 120 mm Hg with < 300 mg of labetalol, incidence of adverse
effects of the drug, including pulmonary edema, hypotension, and maternal
bradycardia. Total intravenous fluid intake exceeding output (+ delta I/O) and
presence or absence of preeclamptic liver involvement were noted. Statistical
analysis included unpaired t-tests and Fisher's exact test. Fifty-one women were
studied, 7 (13.7%) of whom developed pulmonary edema. Demographic and pregnancy
characteristics were not different between patients who did or did not develop
pulmonary edema. No patient had detectable underlying heart disease. Patients
with or without pulmonary edema did not differ as regards entry MAP (130 +/- 14
vs. 129 +/- 18 mm Hg), total dose of labetalol (209 +/- 83 vs. 193 +/- 39 mg/24
hours), incidence of bradycardia or hypotension (0/7 vs. 8/44), or presence of
hepatic involvement (1/7 vs. 9/44). However, there was a significant difference
in degree of positive fluid balance. Patients developing pulmonary edema had a
net gain of 1,466 +/- 429 mL of fluid in the 24 hours in which they received
labetalol than those who did not (659 +/- 1152 mL, P = .003). Initial central
hemodynamic monitoring data revealed no impairment of cardiac performance (mean
cardiac output 7.7 +/- 1.8 L/min, cardiac index 4.0 +/- 0.8 L/min/m2, left
ventricular stroke work index 73 +/- 9 g.m.m-2) despite high pulmonary capillary
wedge pressures (22 +/- 4 mm Hg). We conclude that the incidence of pulmonary
edema in patients with severe preeclampsia who are treated with labetalol appears
to be a result of an increase in third space fluid accumulation as a
manifestation of the severity of their disease, not a direct effect of the drug
on cardiac performance.
PMID- 9642613
TI - Delayed appearance of pulmonary maturation markers is associated with poor
glucose control in diabetic pregnancies.
AB - Fetuses born after pregnancies complicated by diabetes display delayed pulmonary
maturation as measured by the delayed appearance of biochemical indicators of
pulmonary maturity (phosphatidylglycerol, lecithin/sphingomyelin ratio) and by
the occurrence of hyaline membrane disease even in term gestations. We tested the
hypothesis that poor maternal glycemic control is associated with delayed
appearance of the biochemical markers of fetal pulmonary maturation. Consecutive
diabetic pregnancies with documentation of maternal glycemic control and amniotic
fluid analysis for PG were analyzed. Maternal glycemic control was defined as
good if the mean blood glucose was < or = 5.8 mmol/L (105 mg/dl) and poor if >
5.8 mmol/L. The presence of amniotic fluid phosphatidylglycerol was considered an
indicator of lung maturity. Hyaline membrane disease was defined by the criteria
of Corbet et al. [J Pediatr 118:277-284, 1991]. A total of 621 diabetic
pregnancies were analyzed (261 good glycemic control, 360 poor glycemic control).
Phosphatidylglycerol was absent in 21% of good glycemic control vs. 31% of poor
glycemic control pregnancies (P < 0.05). When stratified by gestational age, the
risk of absence of phosphatidylglycerol was significantly higher in the poor
glycemic control group (O.R. 1.83, 1.19-2.84). At 36-37.9 weeks, poor glycemic
control pregnancies had significantly higher rates of absent phosphatidylglycerol
(37% vs. 22%, O.R. 2.04, 1.1-3.9). All cases of hyaline membrane disease beyond
32 weeks gestation occurred in poor glycemic control pregnancies. There were no
cases of hyaline membrane disease beyond 37.0 weeks gestation. We conclude that
poorly controlled maternal glucose levels are associated with delayed appearance
of phosphatidylglycerol in diabetic pregnancies. However, after 37.0 weeks of
gestation, no significant neonatal pulmonary disease occurred.
PMID- 9642615
TI - Effects of smoking, alcohol, and drugs of abuse on the outcome of "expectantly"
managed cases of preterm premature rupture of membranes.
AB - We evaluated the outcome of pregnancies complicated by preterm premature rupture
of membrane (PROM) in order to determine if tobacco, alcohol, or illicit drug
usage were associated with alterations in pregnancy or neonatal outcome.
Comparisons in outcome were made with respect to tobacco, alcohol, and/or illicit
drug usage. Comparisons were made with gestational age (GA) of PROM, GA of
delivery, latency period (LP), maternal age, initial cervical exam (by speculum),
age, race, tocolytic use, chorioamnionitis, and birthweight. Student's t-test,
Mann-Whitney test, and Chi-square analysis were used to evaluate for significant
differences (significance set at P < 0.05). A total of 119 charts were evaluated.
Differences were noted with respect to smokers vs. nonsmokers for latency period
(6.0 days vs. 9.4 days, P < 0.03), age (29.1 years vs. 24.8, P < 0.001), and
gravidity (4.2 vs. 2.8, P < 0.005). Differences were noted for use of alcohol and
age (29.9 vs. 25.2, P < 0.006). Differences were also noted for the use of
illicit drugs and the following variables: age (30.0 vs. 24.9, P < 0.001),
gravidity (4.7 vs. 2.5, P < 0.006), latency (6.2 vs. 9.0, P < 0.009), and parity
(2.6 vs. 1.2, P < 0.01). A difference was noted with respect to cocaine and
latency period (5.8 vs. 9.0, P < 0.01), age (31.2 vs. 24.8, P < 0.001), gravidity
(4.8 vs. 2.9, P < 0.01), and parity (2.6 vs. 1.2, P < 0.03), and the use of
tocolytics (22% vs. 55.4%, P < 0.02). These relationships held after multivariate
analysis was performed. There were no associations among use of tobacco, alcohol,
drugs of abuse, or cocaine and respiratory distress syndrome, intraventricular
hemorrhage, or necrotizing enterocolitis. The use of tobacco during pregnancy
appears to shorten the latency period in pregnancies complicated by PROM. Cocaine
abuse also appears to shorten the latency period. These shortened latency periods
could potentially contribute to increased neonatal morbidity. Larger studies
evaluating this are needed.
PMID- 9642614
TI - Pregnancy complicated by autoimmune polyglandular syndrome type II: a case
report.
AB - Autoimmune polyglandular syndrome may complicate pregnancy and be confused with
hyperemesis gravidarum as a cause of hypoglycemia and electrolyte imbalance in
the first trimester of pregnancy. Autoimmune polyglandular syndromes are uncommon
disorders characterized by the development and presentation of multiple endocrine
and organ dysfunction. To our knowledge, we present the first case of an
autoimmune polyglandular syndrome complicating pregnancy. A 26-year-old woman,
gravida 5 para 3 at 12 weeks gestation, presented with hyperemesis and signs and
symptoms consistent with adrenal insufficiency and hypothyroidism. Evaluation
revealed autoimmune polyglandular syndrome type II. Autoimmune polyglandular
syndromes are a myriad group of diseases characterized by polyglandular
dysfunction. These syndromes should be kept in mind when dealing with pregnant
patients presenting with hyperemesis and an electrolyte imbalance who do not
improve with the usual treatment for hyperemesis. An endocrine dysfunction such
as polyglandular syndrome may exist.
PMID- 9642616
TI - Blood-brain barrier disruption for the treatment of malignant brain tumors: The
National Program.
AB - Chemotherapy delivery for the treatment of malignant brain tumors is markedly
enhanced when given in conjunction with osmotic opening of the blood-brain
barrier. Osmotic opening or disruption of the blood-brain barrier is achieved
while the patient is under general anesthesia, by the infusion of mannitol into
the internal carotid or vertebral artery circulation. The mannitol infusion is
followed by administration of intraarterial chemotherapy. A National Blood-Brain
Barrier Program now exists and includes six universities. Within the National
Program over 4200 blood-brain barrier disruption procedures have been performed
in over 400 patients. Patients with primary central nervous system (CNS)
lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and
metastatic cancer are eligible for treatment. Results in patients with primary
CNS lymphoma, recently reported in the Cancer Journal, include the first example
of a durable response in a primary brain tumor without loss of cognitive function
and without use of radiotherapy. Results with PNET and germ cell tumors are also
very encouraging. Advanced practice nurses coordinate the care of blood-brain
barrier disruption patients. Care includes patients selection, education, close
neurological observation, maintenance of fluid and electrolyte balance and
managing effects of high-dose chemotherapy. Both acute and long-term medical and
psychological follow-up are an essential component of the program, as well as
patient and family support.
PMID- 9642617
TI - Pulmonary management following acute SCI.
AB - Pulmonary complications are the major contributor to mortality and morbidity
following spinal cord injury (SCI), especially during the first year. Patients
who are at increased risk of pulmonary complications include SCI individuals with
cervical and high thoracic injuries, patients with unstable injuries who must be
immobilized, patients with multiple injuries and individuals over the age of 65
years. Although research exists on many of the elements of pulmonary hygiene,
there is a paucity of systematic research linking therapeutic interventions with
patients outcomes during the acute phase following SCI. This area is rich for the
development of collaborative empirical studies which contribute to the science of
preventing pulmonary complications following acute SCI. Research is needed which
tests specific pulmonary hygiene protocols in relation to patient outcomes during
the acute phase of SCI and in the early months after the patient returns home.
PMID- 9642618
TI - Spinal cervical infection: a case report and current update.
AB - Cervical spine infection is a term used to encompass osteomyelitis, discitis and
epidural abscess. Most cases are caused by Staphylococcus aureus but other
organisms have been isolated. The most frequent source is hematogenous spread
from a nearby or distant source. Diagnosis is often confusing. The most common
symptom is worsening back or neck pain that increases with movement. Patients may
have motor or sensory changes if there is compression of the nerve roots or
spinal cord. If the condition is not treated promptly, it may progress to
irreversible neurologic deficit. Positive blood cultures and an elevated
erythrocyte sedimentation rate (ESR) may be seen. Radiologic findings may include
a paravertebral swelling, a destruction of the vertebral end plates and adjacent
portions of the bodies and disc space and the presence of an epidural mass.
Treatment includes radical surgical intervention for debridement and
decompression to stabilize the spine in conjunction with 8-12 weeks of
intravenous antibiotics. Closed continuous local antibiotic irrigation with a
gravity control outflow system has been used.
PMID- 9642619
TI - Elements of empowerment and MS patients.
AB - Elements of empowerment are: cognitive, experiential, ethical, social,
biophysiological, functional and economic. Empirical data from 64 Finnish
multiple sclerosis patients were collected. Based on the data, the social element
is the most dominating element of empowerment. Patient-center research in nursing
care of MS patients should be done to facilitate MS patients abilities toward
empowerment.
PMID- 9642620
TI - Issues related to caring for infants to adults on an integrated epilepsy unit.
AB - We integrated the care of patients of all ages (ranging thus far from 4 weeks to
73 years) in our dedicated 8-bed Epilepsy Unit. Administrative issues pertaining
to admission and discharge criteria, unit policies and procedures and an
interdisciplinary quality assurance plan were examined in relation to the impact
of combining both pediatric and adult patients. Clinical considerations included
the diversified abilities needed to care for pediatric and adult patients both in
relation to the technical skills as well as psychosocial skills required. The
advantages of integrating patients of all ages on one unit include having a staff
highly trained in assessment and intervention skills for a particular disorder.
The psychosocial issues that arise in these patients, regardless of age, tend to
encompass the entire family; therefore a holistic approach is appropriate for
both children and adults. An autonomous nursing practice was established with the
development of critical pathways and patient care protocols. Our experience
suggests that integrated specialized units can enhance the care of patients with
intractable seizures.
PMID- 9642621
TI - Postcomatose unawareness in a brain-injured population.
AB - Different states of unawareness are present following a coma in the brain-injured
population. An attempt to answer three questions is made based on a review of the
literature and multiple case studies: Which type of sensory and motor stimulation
can be suggested? Which instruments can be used to measure behaviors and what are
their benefits and limitation? Does learning theory help explain the postcomatose
unawareness experience? The theoretical paradigm strongly suggests employing
learning theory to target a precise behavior to unmask learning potential and to
use known remediation mechanisms such as errorless learning or implicit learning.
Speculations in the area of unmasking potential are available; these require
intervention to target specific function that could be lost with nonuse.
PMID- 9642622
TI - Copolymer-1 in the treatment of multiple sclerosis.
AB - Recent research in the treatment of multiple sclerosis (MS) has yielded new
therapies. Specifically, copolymer-1, a mixture of synthetic polypeptides
composed of four amino acids has been effective in reducing relapse rates and
disability in patients with relapsing-remitting MS. In a two-year multicenter,
randomized, double-blind, placebo-controlled trial of 251 patients, copolymer-1
was shown to reduce relapses by an average of 29% when compared with placebo.
Sustained disability was also slightly reduced in the copolymer-1-treated group.
The results of the clinical trial indicate that copolymer-1 positively alters the
course of relapsing-remitting MS. With the present availability of copolymer-1,
nurses are challenged to maintain current knowledge of nursing implications,
interventions, patient education and goals for treatment.
PMID- 9642623
TI - Androgen insensitivity syndrome in the era of molecular genetics and the
Internet: a point of view.
AB - The era of molecular genetics has seen the discovery of a great deal of
scientific information about the androgen receptor (AR) and about the many AR
mutations that have been identified in patients with Androgen Insensitivity
Syndrome (AIS). In families with well-characterised mutations, carriers can now
be identified and prenatal testing can be offered. An unexpected finding is that
an AR mutation also causes X-linked spinobulbar muscular atrophy. The intersex
community has established two influential support groups, the AIS Support Group
(which has branches in the UK, North America and Australia) and the Intersex
Society of North America (ISNA). It is ironic that at a time when advances in
biomedical science regarding AIS are a source of pride, these support groups are
accusing the medical profession of having ignored the real needs of patients with
AIS. Since the support groups are willing to assist the medical profession to
develop better approaches to the management of intersex disorders, a
collaborative approach is likely to be mutually beneficial for patients and
physicians. ISNA has alienated many doctors by advocating a radical approach,
namely that surgery should not be performed to 'correct' ambiguous genitalia
until the individual is old enough to express a gender preference. Many children
born in developing countries have either no genital surgery to correct ambiguity,
or surgery is carried out very late. Long term outcome studies, carried out in
developing countries and sensitive to the cultural background, would provide
information on how non-Western societies can accept genital abnormalities that
would be considered unacceptable in the West.
PMID- 9642624
TI - Animal models of type I (insulin-dependent) diabetes mellitus.
AB - Much of our present knowledge concerning the etiopathogenesis, treatment and
prevention of human diabetes would never have been acquired without the study of
animal models of diabetes. The main models of IDDM may be divided into two
groups: induced (through pancreatectomy, chemicals such as alloxan and
streptozotocin, viruses and others) and spontaneous (mainly using BB rats and NOD
mice). The latter, at different ages, develop a diabetic syndrome, with clinical
characteristics, genetics and immunology that are very similar to the human
disease. Among the more significant differences are lymphopenia (in BB rats) and
the predominance of diabetes in females (in NOD mice). Studies aimed at
preventing IDDM have advanced by leaps and bounds by using the two spontaneous
models. These include various methods such as genomic modification, an influence
over some environmental agents, immunosuppression, immunotherapy,
immunomodulation and tolerance induction as well as protection of the beta-cell
from autoimmune attack. The conclusions drawn from animal experiments have
allowed some human trials to be carried out with encouraging results.
PMID- 9642625
TI - Anticardiolipin antibodies in first-degree relatives of type 1, insulin
dependent, diabetic patients.
AB - First-degree relatives (FDRs) of diabetic patients are at risk of IDDM, and
frequently present several autoantibodies. We detected anticardiolipin antibodies
(aCL) in 42 FDRs, aged 12.4 +/- 4.2 years and in 52 controls. aCL (IgG and IgM)
were measured by ELISA and their results expressed in arbitrary units. All FDRs
underwent islet cell antibodies (ICA) measurement, intravenous glucose tolerance
test and HbA1c levels. HLA typing and HLA-DQ molecular analysis were performed in
all FDRs. Positive levels of aCL-IgG were observed in 8/42 FDRs and no control
subject (p = 0.04); aCL-IgM values were similar in FDRs and controls. No
correlation was found between aCL levels and chronologic age or HbA1c levels. No
association was observed between aCL frequency and immunologic (ICA), metabolic
or genetic (HLA) parameters. No FDR showed any feature of antiphospholipid
syndrome. aCL-IgG presence in FDRs is suggestive of a need to carry out a follow
up study to establish the significance of these antibodies.
PMID- 9642626
TI - Insulin secretion and insulin resistance determined by euglycemic clamp.
AB - Obesity among children is increasingly recognized and linked to several metabolic
problems. In this study, 47 children, aged 5-14 yr, with exogenous obesity were
compared to 20 normal (non-obese) children to show alterations in glucose
metabolism. All the obese children had body mass index > 95th percentile and
weight for age > 120%. Basal and stimulated insulin and C-peptide levels were
obtained during oral glucose tolerance test (OGTT). Seven children from the obese
group had impaired OGTT according to WHO criteria. Mean fasting insulin levels
were 26.7 +/- 14.6 microIU/ml in obese and 10.99 +/- 4.36 microIU/ml in controls;
postprandial insulin levels were 70.4 +/- 56.4 microIU/ml and 22.23 +/- 6.55
microIU/ml, respectively (p < 0.001). The euglycemic glucose clamp technique was
applied to 8 normal and 22 obese children. The amount of metabolized glucose (M)
during clamp test is measured to identify glucose sensitivity. Mean M values were
3.24 +/- 1.35 mg/kg/min in obese and 6.525 +/- 0.770 mg/kg/min in control
children (p < 0.001). As a result of this study, it seems reasonable to consider
all obese children and adults as being at risk for hyperinsulinism and insulin
resistance.
PMID- 9642627
TI - Unusual magnetic resonance imaging findings of the sellar region in subjects with
hypopituitarism: report of 4 cases.
AB - Out of 323 consecutive growth hormone deficient patients who underwent magnetic
resonance imaging (MRI), we describe the clinical and neuroradiological
characteristics of four patients in whom MRI revealed unusual pictures of the
sellar area. They were selected as unique in their morphological picture and
representative of rare conditions. At presentation all subjects had short
stature, growth hormone (GH) deficiency and complex phenotypical abnormalities.
Patient 1. Female affected by vaginal atresia and sinus urogenitalis, polydactyly
and syndactyly with Y-shaped metacarpals. MRI at age 11.2 years revealed normal
pituitary, but hypothalamic mass occupying the suprasellar and interpeduncular
cistern. The diagnosis of Hall-Pallister syndrome was made. Patients 2 and 3. Two
sisters with a history of epilepsy both showing mild intellectual deficiency,
midface hypoplasia and ectodermal dysplasia. MRI at age 8 and 12 years
respectively displayed in both cases a round hypointensity protruding from the
dorsum sellae into a normal pituitary. The diagnosis was sellar spine. Patient 4.
Male with a history of postnatal hypoglycemia showing microphallus and clinical
features of severe hypopituitarism. Hormonal evaluation at age 8 months confirmed
multiple pituitary hormone deficiencies and MRI at age 6 years showed absent
anterior lobe, rudimentary stalk and posterior lobe ectopia. The diagnosis was
pituitary aplasia. The patients described show that MRI in pituitary dwarfs can
reveal unusual intrasellar findings and allow the correct diagnosis of rare
syndromes. Our patients also demonstrate the wide variability in the association
of hypopituitarism with midline congenital abnormalities and the possible
combination with complex syndromes.
PMID- 9642628
TI - Growth hormone deficient children treated from before two years old fail to catch
up completely within five years of therapy.
AB - We retrospectively investigated growth response to therapy of 12 patients with
idiopathic growth hormone deficiency (GHD), who received GH (0.6-0.7 IU/kg/week)
in daily subcutaneous injections from before 2 years of age and for a period of
60 months, in order to ascertain whether very early treatment can enable GHD
children to catch-up quickly and completely their initial height deficiency. The
onset of therapy was followed in all patients during the 1st year by a
significant growth spurt, which persisted, even though attenuated, during the
following 4 years. Height deficiency for chronological age (CA) significantly and
progressively decreased during the entire study period (from -3.7 +/- 1.9 to -1.0
+/- 1.0 SDS, p < 0.0025), with a cumulative height gain of 2.7 +/- 1.6 SDS. In
spite of this catch-up growth no patient attained the target percentile by the
5th year of therapy and their average height (CA) was still lower with respect to
the average target height (TH) at the last check-up. Because of the significant
bone age (BA) delay still persisting in most patients, a further and complete
catch-up growth is likely to occur during the next years of treatment, as
suggested by the finding that average height (BA) at the last examination was
higher than average TH. It is concluded that: a) in spite of modern therapeutical
schedules with daily GH injections and frequent adjustments of doses, GHD
children, even though treated from before two years of age, fail to catch-up
completely their initial height deficiency, at least by the 5th year of therapy;
b) a more prolonged treatment is probably needed to allow them to attain their
target percentile. This emphasizes the importance of both early diagnosis and
long-lasting treatment.
PMID- 9642629
TI - Final height in long-term primary hypothyroid children.
AB - OBJECTIVE: We studied retrospectively the statural growth and bone maturation of
32 children with primary hypothyroidism in order to relate their final heights to
their chronological ages, height deficits and bone ages at the beginning of
treatment. Patients were grouped according to age when treatment was started:
Group 1 (G1) (n = 17): (15 girls, 1 boy) 3.09 +/- 0.8 yr; Group 2 (G2) (n = 9):
(7 girls, 2 boys) 9.1 +/- 1.2 yr, and Group 3 (G3) (n = 6): (5 girls, 1 boy)
13.58 +/- 1.13 yr. At diagnosis G1 and G2 were prepubertal and G3 children were
in puberty. In 10 patients of G1, 7 of G2 and 6 (all) of G3 final height was
compared with target height. RESULTS: (SDS) Initial height: G1: -3.74 +/- 1.2;
G2: -3.94 +/- 1.32; G3 -3.65 +/- 1. Height at onset of puberty: G1: -1.06 +/-
1.1; G2: -2.5 +/- 1.4. Height menarche stage 5: G1: -0.63 +/- 1.1; G2: -1.76 +/-
1.2; G3: -2.6 +/- 1.7. Final height: (whole group) G1: -0.85 +/- 0.91; G2: -1.6
+/- 1.3; G3: -2 +/- 1.5. Final height G1 (n = 10): -1.05 +/- 0.89; G2 (n = 7) 1.2
+/- 1. Target height G1 (n = 10): -1.22 +/- 0.78; G2 (n = 7): -0.8 +/- 1.2; G3 (n
= 6): -1.07 +/- 1.5. Initial bone age: G1: -4.9 +/- 0.85; G2: -7.2 +/- 2.6; G3:
4.5 +/- 1.9. Bone age (onset of puberty) G1: -0.26 +/- 1.74; G2: -2 +/- 1.7; Bone
age (menarche) G1: 0.09 +/- 0.6; G2: -0.5 +/- 0.6; G3: -0.76 +/- 0.82.
CONCLUSION: G1 and G2, prepubertal at diagnosis, reached a normal adult height
with respect to target height; G3 did not, the difference being statistically
significant (p < 0.04). Puberty plays a decisive role in the incomplete catch-up
growth of longstanding hypothyroid patients.
PMID- 9642630
TI - Patients with Hashimoto's disease treated with L-thyroxine and followed for three
years.
AB - This study investigated the effectiveness of L-thyroxine management in 32
patients (mean age 11 years and 2 months; M:F = 1:5) with Hashimoto's disease
followed annually for 3 years. One (8%) of the 12 patients, euthyroid at the
onset, never required treatment; of the four (33%) who began treatment
immediately, two were able to stop at the 1st or 2nd follow-up, whereas two had
to continue. The other seven (59%) who did not begin treatment immediately had to
start at the 1st, 2nd or 3rd follow-up. The findings in this small series suggest
that hormone management may prove effective to a certain extent in euthyroid
Hashimoto patients, primarily as a means of prevention.
PMID- 9642631
TI - Onset of obesity in children through the recall of parents: relationship to
parental obesity and life events.
AB - Obesity is a multifactorial disease due to the influence of both genetic and
environmental factors. Parents of 886 obese patients (427 boys and 459 girls,
aged 1-18 years) were investigated by means of a questionnaire in order to study
the factors associated with the onset of obesity in children and the relationship
to genetic background. At presentation obese patients had a very high mean ideal
body weight percent (IBW%) (154 +/- 19%, median 152%, range 120-246). A
significantly higher mean IBW% was found in children of obese parents (one obese
parent: 158 +/- 21%, median 156%, range 120-246; two obese parents 160 +/- 18%,
median 158%, range 123-226) in comparison to children of normal weight parents
(150 +/- 18%; median 147%, range 120-235; p = 0.0001 for children of one or two
obese parents versus children of normal weight parents). Parents of 414 subjects
(46.7%) (Group A) answered that obesity had always been present. The remaining
472 parents (53.3%) (Group B) stated that obesity had had a beginning at a mean
age of 5.3 +/- 2.6 years (median 5.0 years, range 1.0-17.0). No difference was
found in age at presentation, sex distribution, birth weight and number of obese
parents between the two groups. Parents in Group B recalled an event associated
with obesity onset in 197 cases (health event: 119 answers, psycho-social event:
78 answers). Genetic background did not influence this pattern of feedback. In
conclusion, parents of obese subjects seek medical advice when obesity is severe.
Pediatricians should exert strict surveillance on weight from a very young age.
The recall in 22% patients of health or psychosocial events at the onset of
obesity emphasizes that medical counselling is important when the occurrence of
particular events in life may cause erroneous eating habits.
PMID- 9642632
TI - Normal growth in a patient with septo-optic dysplasia despite both growth hormone
and IGF-I deficiency.
AB - A 17 year-old female with septo-optic dysplasia (SOD) and hypopituitarism who has
grown normally despite GH deficiency is presented. Her serum was examined to test
current hypotheses to explain the phenomenon of growth without GH. The patient's
serum possessed potent in vitro growth-promoting activity (GPA) in an erythroid
progenitor-cell clonal proliferation assay consistent with the patient's normal
growth performance. In contrast to previously reported cases of growth without
GH, total IGF-I concentrations were very low in this patient, precluding IGF-I
being responsible for the observed GPA and normal growth pattern. Furthermore,
circulating free IGF-I was also low which is reported for the first time in such
a case. A detailed picture of IGF-binding proteins is also presented. To test the
hypothesis that hyperinsulinemia might be responsible for the observed GPA, in
vitro GPA experiments were performed before and after removal of insulin by
immunodepletion. Neither partial nor complete removal of insulin abolished the in
vitro cell proliferation response. These data demonstrate that neither IGF-I nor
insulin is the factor responsible for GPA in at least this patient with SOD and
growth without GH.
PMID- 9642633
TI - Secondary central precocious puberty in a girl with McCune-Albright syndrome
responds to treatment with GnRH analogue.
AB - GnRH analogues have been used with variable success for the treatment of
precocious puberty in children with McCune-Albright syndrome (MAS). In general,
children with a bone age of less than 13.5 yr have been reported not to have
benefitted from GnRH therapy. In contrast, we have successfully treated a young
girl with MAS and--probably secondary--central precocious puberty using
Decapeptyl, a long acting GnRH analogue. The girl with MAS presented at the age
of six years with cafe au lait spots, osseous lesions and precocious puberty. At
initial presentation height was 130.7 cm (> 97 percentile), weight 27.5 kg (> 97
percentile), Tanner stage B3, PH3. Bone age was 11 yr. Magnetic resonance imaging
of the brain was normal. Endocrine function tests were normal with the exception
of biochemical evidence of central precocious puberty: LHRH test: LH 0.9/20.3,
FSH 4.3/12.7 (mU/ml), E2 15.6 pg/ml. Therapy was started with 3.75 mg GnRH
analogue i.m. every four weeks and was intensified two years after the beginning
of therapy to 3.75 mg i.m. every three weeks. Three years after the start of
treatment bone age was 12 yr and growth velocity was 2.5 cm/year. Tanner stage
was B3, PH3 and LHRH testing revealed biochemical evidence for suppression of
gonadotropins: LH < 0.5/1.0, FSH 1.9/2.5 (mU/ml). We hypothesize that a subgroup
of patients with MAS might present with a central form of precocious puberty.
This may be particularly so in children with a bone age greater than or equal to
11 yr. Central precocious puberty in these children might follow extensive sex
steroid exposure due to the peripheral precocious puberty induced by the
activating mutation of the Gs protein gene. This central form of precocious
puberty responds to therapy with GnRH analogues.
PMID- 9642635
TI - Re: Growth hormone treatment without a needle.
PMID- 9642634
TI - Primary hyperparathyroidism in children: patient report and review of the
literature.
AB - Although primary hyperparathyroidism has rarely been described in pediatric
patients, prompt diagnosis can avoid severe CNS and metabolic consequences. The
aim of this paper is to report a 6 year-old girl whose first symptoms began at
eight days of age with cyanosis, hypotonia, and upward gaze deviation. At 4
months, she was admitted due to neurologic disorders and recurrent infection, but
the definite diagnosis was made only six years later. Her serum calcium levels
are among the highest ever reported in the medical literature, reaching 25.5
mg/dl (6.36 mmol/l). Hypercalcemia, very high levels of parathormone (1550 ng/l-
normal range 10-65) and bone deformities posed no problem to diagnosis when she
first came to our attention. Nephrocalcinosis and impaired renal function were
detected and this child had to be treated with diuretics (furosemide) and
hydration that were able to lower her serum calcium levels. Imaging studies
including 99mTc-sestamibi scan were not diagnostic. At surgery, the four
parathyroid glands were mildly enlarged, with primary hyperplasia. The four
glands were removed, cryopreserved, and 14 fragments (1 mm each) were
autotransplanted to the braquioradial muscle of the left forearm. After a first
phase of hypocalcemia (hungry-bone syndrome), treated with calcium and
calcitriol, the calcium levels stabilized. The question is whether she will
experience some degree of recovery from her neurological problems, since her
severely high calcium levels have been maintained for such a long time.
PMID- 9642636
TI - The molecular genetics of endocrine tumours.
AB - The molecular genetics of endocrine tumours is an area of great interest, due to
the heterogeneity of endocrine tumour types, the association of hormone over
production in some cases, and the wide variation in tumour behaviour. Genes
implicated fall into functional categories such as oncogenes, in which mutations
tend to cause activation, and tumour suppressor genes, in which mutations lead to
loss of function. Oncogenes include the receptor tyrosine kinases such as RET,
signal transduction proteins and other molecules such as cell cycle regulators
and nuclear proteins. Tumour suppressor genes include cell cycle regulators such
as p53 and other molecules such as the MEN 1 gene. Loss of heterozygosity studies
help in the initial localisation of the latter. Endocrine tumours, as with other
tumours, develop as a result of a combination of genetic events, and in the
paediatric age group they often occur in the setting of familial cancer
syndromes. In this review we analyse the main genetic lesions which have been
described in endocrine tumours. There has been an explosion of knowledge in the
last 5 years including the identification of the causative genes for MEN 2 and
most recently for MEN 1. Characterisation of such genes also aids in the study of
somatic mutations in sporadic versions of the same tumour types as occur in the
familial syndromes. Identification of a genetic predisposition to a certain
tumour has management implications that are still to be clarified in most cases,
although in the case of MEN 2 the guidelines for prophylactic thyroidectomy are
generally well accepted.
PMID- 9642637
TI - Frequency and characteristics of lingual thyroid not detected by screening.
AB - Four patients with lingual thyroid glands presenting beyond the neonatal period
have been evaluated at the Hospital for Sick Children, Toronto since the advent
of neonatal TSH screening. All were female, clinically euthyroid at diagnosis and
presented with symptoms of a lingual mass. We estimate that 1.6% of lingual
thyroids are missed by this TSH based thyroid screening program and approximately
1/600,000 live births present in childhood or adolescence with a lingual thyroid.
Physicians should still include lingual thyroid in the differential diagnosis of
a mass at the base of the tongue.
PMID- 9642638
TI - Thyroxine screening values in premature infants.
AB - OBJECTIVES: Premature infants often have low thyroxine levels when compared to
fullterm infants. We sought to determine gestational age specific normal ranges
for thyroxine screening results for premature infants in neonatal intensive care
units. METHODS: Thyroid screening results for infants less than 38 weeks
gestation admitted to two NICUs were examined. For each sample the thyroxine Z
score was computed using parameters from fullterm infants. The mean thyroxine Z
score was calculated for each gestational age for days of life 1, 2, 3-7, 8-14,
15-21, 22-28, and 29-60. RESULTS: There were 1144 specimens obtained from 543
premature infants. The mean thyroxine Z-score was below 0 for almost every
gestational age and days-of-life category. The mean thyroxine Z-score increased
with gestational age, but did not rise with increasing postpartum age.
CONCLUSION: The data show that normal thyroxine Z-scores for premature infants
are lower than for fullterm infants and remain low at least as long as the
infants remain ill.
PMID- 9642639
TI - The association of congenital hypothyroidism and congenital gastrointestinal
anomalies in Down's syndrome infants.
AB - OBJECTIVE: To study the prevalence of congenital hypothyroidism in infants with
Down's syndrome and to verify whether there is an association with other
congenital defects. METHODS: This is a prospective study of 112 Down patients,
less than 1 year of age, who attended Songklanagarind Hospital from January 1991
to December 1996. Free T4 and TSH determinations were performed in all Down
infants. Information on karyotype, sex, maternal age and other congenital
anomalies was collected. RESULTS: Congenital hypothyroidism was detected in 17
patients (15.2%); 3 overt congenital hypothyroidism; 6 persistent compensated
hypothyroidism; and 8 transient compensated hypothyroidism. Nine of the 20
patients (45%) with congenital gastrointestinal anomalies had congenital
hypothyroidism, while 8 out of 92 patients (8.7%) without congenital
gastrointestinal anomalies had congenital hypothyroidism. The odds ratio was 8.59
(95% confidence interval 2.4-31.6; p = 0.0001). CONCLUSION: Congenital
hypothyroidism has a relatively high prevalence rate in Down infants and tends to
occur in Down patients with gastrointestinal anomalies.
PMID- 9642640
TI - Growth stunting in early life in relation to the onset of the childhood component
of growth.
AB - AIMS: Growth stunting is prevalent in developing countries. The prevalence of
stunting ranges from 10-80% or more. The critical period for growth faltering in
length is between six and 18 months. The aims of this study were 1) to
investigate the association between the age at onset of the childhood component
and growth stunting in early life; 2) to develop a screening method for
identifying any individual infant subject to stunting in early life. MATERIALS &
METHODS: This community-based longitudinal study was carried out in Lahore,
Pakistan. Three studied areas and one local control group were included in the
study. There were 425 subjects for whom data were available for determining the
age at onset of the childhood component. The onset was defined as an abrupt
increase in length velocity. It was determined individually using the infancy
childhood-puberty growth model. RESULTS: The medians of the age at onset of
childhood component were 15, 13, 10 and 9 months in the periurban, village, urban
and control groups, respectively. The onset was significantly related to both
length and length velocity during the critical period of stunting. Based on the
distribution of individual length increment from 12 to 15 months, 2.0 and 3.0 cm
were chosen as the cut-off points to identify a stunting infant. In the normal
onset group, 84% of the children were identified as growing normally; in the
delayed onset group, 61% were identified as stunting. Using this screening
method, 97% of children have a delayed onset if their length increase is below 2
cm from 12 to 15 months; 99% of them have a normal onset if the increase is above
3 cm over the same period. CONCLUSIONS: The age at onset of the childhood
component can significantly explain the variations in both length and length
velocity in early life. The stunting screening method reported here is simple. It
can be used in almost any situation, such as a pediatric clinic or community
based survey.
PMID- 9642641
TI - Pseudopapilledema and congenital disc anomalies in growth hormone deficiency.
AB - Optic nerve hypoplasia is a congenital disc anomaly associated with growth
hormone deficiency (GHD). Pseudotumor cerebri is an adverse event associated with
growth hormone treatment (hGH) and manifested by increased intracranial pressure
and papilledema. Pseudopapilledema is a generic ophthalmologic term encompassing
several conditions, including congenital disc anomalies. It is benign and can be
distinguished from papilledema by physical examination. The objective of this
report is to document that congenital disc abnormalities, which can be confused
with papilledema, occur in children with GHD. Three patients with GHD had
fundoscopic examinations suggestive of papilledema and possibly pseudotumor
cerebri. The abnormal optic nerves were characteristic of pseudo-papilledema, and
appear to be a variant of optic nerve hypoplasia. The finding of optic disc
abnormality during hGH may reflect pseudo-papilledema and not pseudotumor
cerebri. Of equal importance, the reported patients indicate that the finding of
pseudopapilledema in short children should suggest the possibility of GHD.
PMID- 9642642
TI - Prevention of diabetes in non-obese diabetic (NOD) mice by short-term and high
dose IGF-I treatment.
AB - This report describes the results of IGF-I treatment in a NOD mouse colony with a
high incidence of overt diabetes. The animals were treated with IGF-I 17.9
nmol/day at 28-41 days of age and 35.9 nmol/day at 42-69 days of age and observed
up to 280 days of age. Three of 12 (25%) IGF-I-treated animals developed diabetes
compared with 8 of 11 (73%) controls (P < 0.05). The severity of insulitis at the
conclusion of the follow-up was less pronounced in non-diabetic treated animals
than in non-diabetic controls. These data support previous findings that IGF-I
treatment protects the pancreatic beta-cells from destruction by diabetic
autoimmunity in NOD mice.
PMID- 9642643
TI - Thyroid abnormalities as a feature of DiGeorge syndrome: a patient report and
review of the literature.
AB - DiGeorge syndrome or anomaly consists of a developmental field defect which is
characterized by congenital absence or hypoplasia of the thymus and parathyroids,
as well as facial dysmorphism and congenital heart defects. Other congenital
malformations may coexist, in particular, thyroid abnormalities. A case of
congenital hypothyroidism and DiGeorge syndrome is reviewed. Necropsy, clinical,
and experimental studies also show that thyroid abnormalities may be a feature of
DiGeorge syndrome. Although this could be purely coincidental, our case suggests
that thyroid gland dysgenesis may be more common than previously thought. Thus,
children with the DiGeorge syndrome may be at higher risk for hypothyroidism.
Because of this potential association, patients who are considered to have this
anomaly should have early newborn thyroid screening.
PMID- 9642644
TI - Persistent neonatal hypoglycemia: an unusual finding of congenital
hypothyroidism.
AB - We report a newborn infant who has congenital hypothyroidism associated with
profound and persistent neonatal hypoglycemia. Persistent and marked hypoglycemia
has not been previously reported in congenital hypothyroidism to our knowledge.
The cause of this condition may be reduced glyconeogenesis or insulin clearance.
PMID- 9642645
TI - Non-insulin dependent diabetes mellitus in a prepubertal child with Prader-Willi
syndrome.
AB - Diabetes mellitus has only rarely been reported in prepubertal children with
Prader-Willi syndrome. All reported children have required insulin therapy. We
report the development of a previously unrecognized association of non-insulin
dependent diabetes mellitus in an obese 6 year-old child with Prader-Willi
syndrome. She has never developed ketosis or acidosis, and she has been treated
with oral hypoglycemic medication.
PMID- 9642646
TI - Growth and developmental follow-up forms.
PMID- 9642647
TI - Carbohydrates as a cerebral metabolic fuel.
AB - The human brain is an extremely active metabolic organ with little endogenous
stores of energy. It is thus dependent on circulating glucose to fuel metabolism
and support cognitive functioning. However there is growing evidence that the
human brain is able to utilise other non-glucose fuels during times of glucose
lack. We review the evidence for the potential of the human brain to use the
alternate fuels lactate and beta-hydroxybutyrate, and some recent studies
examining the ability of regions of brain to use non-glucose lipid fuels. The
human brain does not seem to have the ability to use the gluconeogenic precursor
alanine to any significant degree. Regionality within the brain can be examined
in vivo by the use of positron emission tomography, which offers the exciting
prospect of studying human brain metabolism in vivo using a simple and non
interventional technique. Increased understanding of the brain's metabolism, the
way in which hypoglycaemia is recognised and the manner in which this can be
altered in the syndrome of hypoglycaemia unawareness and deficient
counterregulation will help develop further strategies to prevent the clinical
problems associated with hypoglycaemia in insulin-dependent diabetic adults and
children.
PMID- 9642648
TI - Counterregulatory mechanisms to insulin-induced hypoglycemia in humans: relevance
to the problem of intensive treatment of IDDM.
AB - Hypoglycemia unawareness is a condition of decreased/absent perception of
specific symptoms which normally inform the subject that plasma glucose is
decreasing to dangerous levels resulting in neuroglycopenia. This syndrome is
frequent in IDDM. In the absence of warning symptoms, IDDM patients cannot take
any measure (e.g. eating) to prevent severe neuroglycopenia (unconsciousness).
Because hypoglycemia unawareness is associated with impaired glucose
counterregulation, especially reduced adrenaline responses, hypoglycemia
unawareness is a risky condition for severe hypoglycemia. A number of studies in
animals and humans indicate that hypoglycemia unawareness is largely, if not
fully, secondary to recurrent or chronic hypoglycemia. Meticulous prevention of
hypoglycemia in IDDM largely recovers the symptoms of hypoglycemia and the
responses of adrenaline. It is important that diabetologists and IDDM patients
are familiar with the syndrome of hypoglycemia unawareness and learn how to
prevent/treat it in programs of intensive therapy. Intensive therapy aiming
strictly at normoglycemia may increase the frequency of hypoglycemia and
hypoglycemia unawareness. On the other hand, if intensive therapy is combined
with a program of prevention of hypoglycemia, the percentage of HbA1c can be
maintained long-term below 7.0% (i.e. below values risky for onset/progression of
complications), and at the same time the frequency of hypoglycemia is very low.
Under these conditions, IDDM patients maintain the awareness of warning symptoms
and adrenaline response to hypoglycemia, a vital back-up system for the safety of
intensive therapy of IDDM.
PMID- 9642649
TI - Hypoglycemia due to hormone deficiencies.
PMID- 9642650
TI - Ions and genes in persistent hyperinsulinaemic hypoglycaemia in infancy: a
commentary on the implications for tailoring treatment to disease pathogenesis.
PMID- 9642651
TI - Persistent hyperinsulinemic hypoglycemia of infancy: long-term results.
AB - Data from 15 infants with persistent hyperinsulinemic hypoglycemia of infancy
(PHHI), presented to our hospital from 1976 to 1995, were retrospectively
analyzed. Nine patients were successfully managed with prolonged (1.25-13 yr)
diazoxide therapy and frequent, low protein feeds. Three of them are still being
treated with diazoxide, 7.75, 9.25 and 13 yr post diagnosis. Four patients were
managed only with frequent, low protein feeds. One patient had 2/3
pancreatectomy, and another had excision of a focal lesion which proved to be
focal nesidioblastosis. Two patients were lost to follow up. No patient has shown
neurological damage. One girl developed seizures at age 11.5 yr without
hypoglycemia. The patient with 2/3 pancreatectomy developed diabetes mellitus at
the age of 20 years. Although conservative management of PHHI is very laborious
for the family and the physician, it should be applied as long as euglycemia is
accomplished. Definition of the anatomical lesion (focal or diffuse) prior to
pancreatectomy is recommended.
PMID- 9642652
TI - Preoperative use of octreotide in a newborn with persistent hyperinsulinemic
hypoglycemia of infancy.
AB - In this paper, we describe a newborn diagnosed with persistent hyperinsulinemic
hypoglycemia of infancy (PHHI) at two days of age. She presented with severe
asymptomatic hypoglycemia and required both a high rate of glucose infusion and
diazoxide treatment. On the 9th hospital day, due to persistent and intractable
hypoglycemia, subcutaneous octreotide treatment was initiated. This treatment
reduced the rate and concentration of glucose needed to be infused but the
hypoglycemia did not subside totally. On the 18th hospital day near-total
pancreatectomy was performed. Tachyphylaxis resulting from continuous use of
octreotide limited its effect but enabled us to keep the patient euglycemic
preoperatively.
PMID- 9642653
TI - Hypoglycemia in childhood: a clinical approach.
AB - A child with hypoglycemia presents very frequently an urgent diagnostic and
therapeutic challenge. The main causes of hypoglycemia and the clinical approach
and laboratory investigations are reviewed underlining that the relationship
between the hypoglycemic event and the last meal can aid in diagnosis, in
particular for metabolic diseases. Only a correct and precise diagnosis can allow
adequate and appropriate treatment and prevention of future hypoglycemic events.
PMID- 9642654
TI - Hypoglycemia during intensified insulin therapy of young children.
PMID- 9642655
TI - Hypoglycaemia during intensified insulin therapy of children and adolescents.
AB - Good metabolic control prevents or at least postpones late vascular
complications, but several studies indicate that such good metabolic control
cannot be reached without simultaneous increase in the incidence of severe
hypoglycaemia. We have been able to reduce late complications through multiple
insulin therapy adjusted on the basis of active self control combined with active
psychosocial support and education. A prospective regular registration of all
hypoglycaemic incidents in about 130 diabetic children and adolescents shows that
in spite of reasonably good HbA1c values (mean and median 6.9%, corresponding to
7.9% with the DCCT method), we have less incidence of severe hypoglycaemia (13-17
per 100 patient years) than reported in other recent studies (20-25 per 100
patient years). We saw no correlation between HbA1c and severe hypoglycaemia, but
most hypoglycaemia was caused by mistake or reasons not related to degree of
metabolic control. Our conclusion is that there is no inevitable relation-ship
between low HbA1c and hypoglycaemia. Instead hypoglycaemia should be prevented
parallel to and in the same way as we try to reach good metabolic control.
PMID- 9642656
TI - Problems of hypoglycemia arising in children and adolescents with insulin
dependent diabetes mellitus. The Diabetes Study Group of The Italian Society of
Pediatric Endocrinology & Diabetes.
AB - Hypoglycemic episodes were studied in two large populations of prepubertal (332
subjects, aged 6-11 years) and adolescent (200 subjects, aged 12-18 years)
diabetic children. We confirmed the majority of published data on incidence and
causes of hypoglycemia and added some new information on the complex
symptomatology and fear of hypoglycemia. Longer duration of IDDM induced a change
in the symptomatology of hypoglycemia, consisting of a reduced occurrence of
autonomic symptoms, namely tremor, and a parallel increased experience of
neuroglycopenic symptoms, particularly drowsiness, difficulty in concentrating,
and lack of coordination. The latter symptoms were found more frequently in
patients with partial unawareness, more severe episodes and higher fear of
hypoglycemia. These observations draw attention to the neuroglycopenic symptoms
as important warning cues of hypoglycemia. We emphasized the necessity of
observing the change in the frequency of symptoms experienced by patients, in
particular autonomic and neuroglycopenic symptoms, in order to educate patients
to preserve a normal awareness of hypoglycemia and prevent severe episodes.
PMID- 9642657
TI - Hypoglycemia in children with diabetes: incidence, counterregulation and
cognitive dysfunction.
AB - Hypoglycemia remains a critical problem in the treatment of IDDM and often limits
our ability to consistently achieve excellent glycemic control. Ongoing studies
will be important to increase our understanding of the factors responsible for
its occurrence and the impact that hypoglycemia may have, particularly for the
brain. Significant differences have been documented between adults and children
in the incidence of this complication of insulin therapy as well as in the
counterregulatory hormone responses to hypoglycemia and its effects on the CNS.
While children with diabetes still need insulin treatment, the prevention of
hypoglycemia will be a central aim of management. This will depend on effective
and expert diabetes education and support for the patient and his or her family
along with better efforts to achieve more physiological insulin replacement.
PMID- 9642658
TI - High incidence of hypoglycemic episodes with neurologic manifestations in
children with insulin dependent diabetes mellitus.
AB - Hypoglycemia is a serious frequent complication of insulin therapy in type 1
diabetes. PATIENTS AND METHODS: We surveyed 139 IDDM patients. RESULTS: Forty
four patients (32%) reported at least one severe hypoglycemic episode. All
patients with severe hypoglycemia experienced neurological manifestations.
Symptoms included confusion and abnormal behavior, convulsions, coma, transient
hemiparesis and one case of permanent hemiparesis. Most episodes occurred at
night or during morning hours. 44% of episodes were related to delayed meal or
snack, 11% to excess insulin administration and 13% to extra physical activity.
HbA1c was significantly lower in patients with severe hypoglycemia compared with
diabetic controls (7.33 +/- 1.09% and 9.45 +/- 4.32%, respectively).
PMID- 9642659
TI - Maternal fear of hypoglycemia in their children with insulin dependent diabetes
mellitus.
AB - A modified version of the Hypoglycemia Fear Survey (HFS) was used to measure fear
of hypoglycemia among mothers of 46 pre-adolescent children with IDDM.
Glycosylated hemoglobin (HbA1) levels were measured, and episodes of severe
hypoglycemia over the previous year were recorded. The relationships between the
child's age, disease duration, HbA1, history of hypoglycemia, and maternal
distress concerning hypoglycemia and HFS-P scores were explored. Maternal HFS-P
scores were also compared to those of 78 IDDM adults. There was no relationship
between children's age, disease duration, number of severe hypoglycemic episodes
and maternal HFS-P scores. However, mothers whose children had passed out with
hypoglycemia had higher HFS-P scores. Correlations between mothers' responses
concerning their children's history of hypoglycemia and HFS-P scores suggested
that their degree of distress associated with events which occurred when their
child was asleep, or in a social situation was related to their total HFS-P, and
Behavior and Worry subscores. Mothers demonstrated significantly greater fear
than did adult patients themselves. The HFS-P may be an appropriate instrument
for examining the psychological impact of differing treatment regimens on
families of children with IDDM.
PMID- 9642660
TI - Advances and controversies in etiopathogenesis of type 1 (insulin-dependent)
diabetes mellitus.
AB - The present state of knowledge and controversies about the etiopathogenesis of
tyep 1 diabetes can be summarized as follows: GENETICS: MHC class II genes
(IDDM1) confer the strongest susceptibility with a hierachy DQ > DR; more than
ten other chromosome regions (IDDM2 to IDDM13) have been identified as candidates
for linkage with type 1 diabetes: currently, there is consensus for insulin
(IDDM2) and a few other loci, while the remainder await confirmation.
ENVIRONMENT: The role of milk as a trigger is debated. In fact, the protective
effect of breast feeding is marginal, while the immune response to milk proteins
in type 1 diabetics is very heterogeneous; moreover, the putative autoantigens
showing sequence homology with milk proteins have been questioned. With regard to
viruses, seasonal variations of incidence have been confirmed, although not
uniform across countries; serological studies are controversial, while isolation
of viruses from diabetic pancreases remains anecdotal; very interesting is the
demonstration of enteroviral infection in pregnant mothers of future diabetic
children, although this does not prove a causal role; a new frontier of
investigation could be that of endogenous retroviruses acting either as
autoimmune genes or infectious agents. AUTOIMMUNITY: GAD65, IA2 and insulin are
at present the only established autoantigens; autoantibodies to these molecules,
used in combination with ICA, can accurately predict type 1 diabetes; B
lymphocytes and autoantibodies might play a pathogenetic role; autoantigen
targets of T-lymphocytes are yet to be characterized; assays for measuring
autoreactive T-lymphocytes require standardization; antigen-specific Th1/Th2
relationship in type 1 diabetes remains controversial.
PMID- 9642661
TI - Controversies on humoral immune markers of insulin-dependent diabetes mellitus.
PMID- 9642662
TI - Epidemiology of IDDM: recent advances.
PMID- 9642663
TI - Controversies on the prevention of insulin-dependent diabetes mellitus by
immunomodulation: lessons from NOD mice treated with beta-1,6;1,3-D-glucan and
rhIGF-I.
PMID- 9642664
TI - Recommended dietary allowances (RDA) in the dietary management of children and
adolescents with IDDM: an unfeasible target or an achievable cornerstone?
AB - A diet in line with RDAs is seldom achieved by IDDM patients. High post-prandial
glucose levels are often attributed to food excess rather than to inadequate
insulin doses. Lower dietary CHO with greater fat (in particular SFA) and protein
are progressively scheduled instead of increasing insulin units. We studied 194
IDDM patients (1-23 yr) on a diet conforming to RDAs with a restriction of
sucrose and without a quantitative approach and exchange lists of food for one
year. The diet consisted of a high intake of starchy foods and vegetables and a
restricted amount of animal products. HbA1c mean values of the year were used as
an indicator of metabolic control. The mean daily insulin dose was 0.53 U/kg in
patients with diabetes duration (DD) < 2 yr and 0.81 U/kg in those with DD > 2
yr. Mean annual HbA1c was 7.1 +/- 0.9%. The prevalence of obesity was low (5.7%).
Adolescent females were more obese than males. A dietary approach in line with
RDA requirements, that may help prevent any complications related to an
inappropriate diet pattern, coupled with a dynamic insulin adjustment, is the
first-line intervention to prevent complications in IDDM patients.
PMID- 9642665
TI - Controversies on the pathogenesis of diabetic angiopathy: which treatment for
normotensive adolescents with microalbuminuria and type 1 diabetes?
AB - Between 5 and 20% of children with type 1 diabetes may develop microalbuminuria
as a sign of incipient nephropathy starting in early puberty. Permanent
microalbuminuria has to be distinguished from intermittent and transient
microalbuminuria with unknown prognostic relevance. A review of clinical risk
factors, retinal examination and an ambulatory 24-h blood pressure profile are
recommended. Non-pharmacological interventions such as the improvement of
glycemic control, the cessation of smoking or the feasibility of a low protein
diet should always be considered. Concerning pharmacological intervention, in
particular ACE-inhibitors have been shown to be beneficial in adolescents with
hypertension but may also be renoprotective in normotensive patients with
microalbuminuria. However, long-term studies with ACE-inhibitors in normotensive
patients have shown negligible changes in the glomerular filtration rate, which
better reflects the renal status during treatment than changes in the albumin
excretion rate. Nevertheless, such treatment is currently recommended also for
normotensive adolescents if other interventions are not successful.
PMID- 9642666
TI - Controversies on the prevention of diabetic nephropathy.
AB - Renal function declines progressively in patients with diabetic nephropathy and
the decline may be slowed by some preventive interventions. Optimized and
intensive insulin therapy delays the onset and slows the progression of diabetic
nephropathy. Moreover, dietary restriction, avoiding a high protein intake, could
be effective in reducing glomerular hyperfiltration. Finally, there is evidence
that angiotensin-converting enzyme inhibitors reduce renal damage by one or more
mechanisms independent of their antihypertensive effects. Some controversial
aspects of the prevention of diabetic kidney disease are presented and discussed.
PMID- 9642667
TI - IDDM prevention trials in progress--a critical assessment.
PMID- 9642668
TI - It's "all in the family": responsibility for diabetes care.
AB - Despite its importance, diabetes management it is an area of great difficulty for
children and adolescents. As children reach the teenage years, satisfactory
levels of treatment adherence and glycemic control become increasingly difficult
to obtain. In order to promote better diabetes care, the present paper emphasizes
the need for families to remain actively involved in their youngster's diabetes
care, regardless of the child's age. Recent studies of children and adolescents
with diabetes are described that support the view that, even as responsibility
for diabetes care shifts from a parent-managed to an adolescent-managed system,
family members should remain actively involved in day to day management. Based on
current research efforts, the specific ways that family members can remain active
and involved are discussed.
PMID- 9642669
TI - GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine
hydrochloride] and the anticonvulsive activity of conventional antiepileptics
against pentetrazol in mice.
AB - Excitatory amino acids participate in the generation of seizure activity.
Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8
methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate
mediated events, on the protective activity of conventional antiepileptic drugs
against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, i.p.) did not
affect the clonic phase of pentetrazol (injected s.c. at its CD97 of 90 mg/kg)
convulsions. Only the antipentetrazol activity of valproate (100 mg/kg) was
enhanced by GYKI 52466 (10 mg/kg)--the percentage of mice protected was
significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam
(at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/kg) was not
modified by GYKI 52466 (up to 10 mg/kg). The combination of valproate (100 mg/kg)
with GYKI 52466 (10 mg/kg) did not affect the performance of mice evaluated in
the chimney test. However, this combination resulted in significant memory
deficits, measured in the passive avoidance task. In no case did GYKI 52466 (10
mg/kg) affect either total or free plasma levels of antiepileptic drugs (as
measured by immunofluorescence), so a pharmacokinetic interaction is not
probable. Finally, the interaction of the non-NMDA receptor antagonist with
antiepileptic drugs does not seem promising in the pentetrazol test, recognized
as a model of human myoclonic epilepsy.
PMID- 9642670
TI - The effect of glutamate and inhibitors of NMDA receptors on postdenervation
decrease of membrane potential in rat diaphragm.
AB - The early postdenervation depolarization of rat diaphragm muscle fibers (8-10 mV
within 3 h in vitro) is substantially smaller (3 mV) when muscles are bathed with
1 x 10(-3) M L-glutamate (Glu) or 1 x 10(-3) M N-methyl-D-aspartate (NMDA). The
effects of Glu and NMDA are inhibited in a dose-dependent manner by competitive
inhibitor 2-amino-5-phosphonovaleric acid (APV) with Ki 6.3 x 10(-4) M, by 2 x
10(-7) M MK-801, which acts as an open channel inhibitor, by 2-3 x 10(-4) Zn2+,
which reacts with surface-located sites of the NMDA subtype of the glutamate
receptor, and also by glycine-free solutions and 7-Cl-kynurenic acid, which
inhibits the glycine binding sites on NMDA receptors. It follows that the effect
of glutamate on early post-denervation depolarization is mediated by the NMDA
subtype of glutamate receptor with similar pharmacological properties to those
found in neurons. The only exception found was the glutamate-like action of 1 x
10(-7) M MK-801, which partially prevented the early postdenervation
depolarization when present in the muscle bath during the first 3 h after nerve
section.
PMID- 9642671
TI - Changes of acetylcholinesterase activity in various parts of brain following
nontreated and treated soman poisoning in rats.
AB - Changes of acetylcholinesterase (AChE) activity in various parts of the brain
(frontal cortex, medulla oblongata, pons Varoli, cerebellum, hypothalamus, and
hippocampus), following im sublethal non-treated and treated soman poisoning were
studied. As a treatment, two antidotal mixtures containing atropine and either
obidoxime or oxime HI-6 were used. This antidotal treatment was administered im
for 30 s following soman intoxication. The AChE activities in the various brain
tissues were evaluated at 1 and 3 h following soman administration. As expected,
the highly toxic organophosphorus compound, soman, markedly inhibited AChE
activity in all the brain sections at both time intervals. Both oximes had little
influence on soman-induced AChE inhibition, but only the HI-6 mixture was able to
reactivate soman-inhibited AChE significantly in some of the brain parts (frontal
cortex, pons Varoli, hypothalamus). In the brain, the effect of HI-6 against
soman-induced AChE inhibition is higher in comparison with obidoxime, but not
quite satisfactory. Despite its limited effectiveness in the brain, HI-6 seems to
be the most effective oxime yet found against soman poisoning because of its high
reactivating effect in the peripheral compartment and other beneficial effects.
PMID- 9642672
TI - Dual response of calpain to rat brain postdecapitative ischemia.
AB - Calpains, Ca(2+)-dependent neutral proteinases (microM and mM Ca(2+)-sensitive),
and their endogenous inhibitor calpastatin were examined in rat brain. Specific
activity of m-calpain exceeded almost 10 times that of mu-calpain, and the both
isoforms of calpain together with calpastatin were mainly located in the soluble
fraction of homogenate. Acute postdecapitative ischemia of 15 min duration
resulted in a gradual, time-dependent decrease of total mu-calpain activity (to
60% of control values) and in the moderate elevation of calpastatin activity (by
28%). The decrease of total mu-calpain activity coincided with its remarkable
increase (above 300% of control values) in particulate fraction. In the case of m
calpain, the only observed effect of ischemia was its redistribution and, as a
consequence, the elevation of activity in particulate fraction. The accumulation
of breakdown products, resulting from calpain-catalyzed proteolysis of fodrin (as
revealed by Western blotting) indicated activation of calpain under ischemia. The
findings suggest that this rapid activation involves partial enzyme translocation
toward membranes, and is followed (at least in acute phase) by mu-calpain
downregulation and increased calpastatin activity.
PMID- 9642673
TI - Distribution and isoform diversity of the organellar Ca2+ pumps in the brain.
AB - The gene family of organellar-type Ca2+ transport ATPases consists of three
members. SERCA1 is expressed exclusively in fast skeletal muscle; SERCA2 is
ubiquitously expressed, whereas SERCA3 is considered to be mainly expressed in
cells of the hematopoietic lineage and in some epithelial cells. In the brain,
the organellar-type Ca2+ transport ATPases are almost exclusively transcribed
from the SERCA2 gene. Four different SERCA2 mRNAs have been described (classes 1
4). However, unlike in nonneuronal cells, which express the class 1, 2, and 3
splice variants, the main SERCA2 mRNA in the brain is the class 4 messenger.
Similar to classes 2 and 3, the class 4 codes for the ubiquitously expressed
SERCA2b protein. Recently, we have reported the distribution of the SERCA
isoforms in the brain (Baba-Aissa et al., 1996a,b). SERCA2b was present in most
neurons of all investigated brain regions. The highest levels were found in the
Purkinje neurons of the cerebellum and in the pyramidal cells of the hippocampus.
Interestingly, SERCA3 and SERCA2a are coexpressed along with SERCA2b in the
Purkinje neurons, but are weakly expressed in the other brain regions if present
at all. Since these three protein isoforms have a different affinity for Ca2+,
their possible roles in relation to Ca2+ stores in neurons are discussed.
PMID- 9642674
TI - Decreased expression of natriuretic peptide A receptors and decreased cGMP
production in the choroid plexus of spontaneously hypertensive rats.
AB - Atrial natriuretic peptide receptor (ANP) subtypes and their signal transduction
response were characterized in choroid plexus of spontaneously hypertensive (SHR)
and normotensive (WKY) rats. We found two ANP receptor subtypes, guanylate
cyclase coupled and uncoupled, in both rat strains. Binding of ANP was lower in
SHR choroid plexus when compared to WKY. The lower ANP binding in SHR was the
result of a decrease of binding to the guanylate cyclase-coupled receptor subtype
A, a decrease that correlated well with the decreased ANP-induced cGMP formation
in SHR. Forskolin stimulated cGMP production to the same extent in both strains.
In WKY rats, ANP increased basal and forskolin-stimulated cAMP production;
conversely, in SHR, ANP did not affect the basal level of cAMP and inhibited the
forskolin-stimulated cAMP production. These results demonstrate differences in
ANP receptor subtype expression, and ANP signal transduction in choroid plexus of
hypertensive and normotensive rats, which is of possible significance to the
central mechanisms of blood pressure control.
PMID- 9642675
TI - Mechanisms of hippocampal reoxygenation injury.
AB - Mechanisms of 12 min of hypoxia and subsequent reoxygenation were studied in rat
hippocampal slices. General cell injury in reoxygenation was indicated by
increased lactate dehydrogenase (LDH). Increase in conjugated dienes (CD) showed
that oxygen radical burst induced lipid peroxidation (LPO). ATP increase was also
involved in reoxygenation injury, since cyanide, an inhibitor of ATP synthesis,
decreased this damage. The results obtained on using inhibitors of oxygen
radicals generation, i.e., allopurinol, indomethacin, rotenone, and antimycin A,
strongly suggest that the sources of oxygen radicals were the xanthine/xanthine
oxidase system, prostaglandin synthesis, and mitochondrial respiratory chain. The
involvement of oxygen radicals in oxidative stress was confirmed also by using
chain-breaking antioxidants, trolox alpha-tocopherol and stobadine, [(-)-cis-2,8
dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido (4,3b)indole]. Stobadine added at the
onset of reoxygenation was most effective, acting in a dose-dependent manner and
found to be without effect when applied in hypoxia. Cytochrome-c oxidase was
decreased in reoxygenated hippocampal slices treated with stobadine.
PMID- 9642676
TI - Neurochemical changes in the spinal cord in degenerative motor neuron diseases.
AB - Human amyotrophic lateral sclerosis (ALS), a typical motor neuron disease, is
characterized pathologically by selective degenerative loss of motoneurons in the
CNS. We have demonstrated significant reductions of neurotransmitter-related
factors, such as acetylcholine-(ACh)-synthesizing enzyme activity and glutamate
and aspartate contents in the ALS, compared to the non-ALS spinal cord obtained
at autopsy. We have also shown considerable reductions in activities of
cytochrome-c oxidase (CO), an enzyme contributing to aerobic energy production,
and transglutaminase (TG), a Ca(2+)-dependent marker enzyme for tissue
degeneration, in the ALS spinal cord. We found marked increases in fragmented
glial fibrillary acidic protein (GFAP), a filamentous protein specifically
associated with reactive astrocytes, in the ALS spinal cord relative to non-ALS
tissue. These biochemical results corresponded well to pathomor-phological
neuronal degenerative loss and reactive proliferation of astroglial components in
the ALS spinal cord tissue. However, these results only indicate the final
pathological and biochemical outcomes of ALS, and it is difficult to follow up
cause and process in the ALS spinal cord during progression of the disease.
Therefore, we used an animal model closely resembling human ALS, motor neuron
degeneration (Mnd) mutant mice, a subline of C57BL/6 that shows late-onset
progressive degeneration of lower motor neurons with paralytic gait beginning
around 6.5 mo of age, to follow the biochemical and pathological alterations
during postnatal development. We detected significant decreases in CO activity
during early development and in activity of superoxide dismutase (SOD), an
antioxidant enzyme, in later stages in Mnd mutant spinal cord tissue. TG activity
in the Mnd spinal cord showed gradual increases during early development reaching
a maximum at 5 mo, and then tending to decrease thereafter. Amounts of fragmented
GFAPs increased continuously during postnatal development in Mnd spinal cord.
These biochemical changes were observed prior to the appearance of clinical motor
dysfunctions in the Mnd mutant mice. Such biochemical analyses using appropriate
animal models will be useful for inferring the origin and progression of human
ALS.
PMID- 9642677
TI - Tyrosine hydroxylase mRNA levels in locus ceruleus of rats during adaptation to
long-term immobilization stress exposure.
AB - The major central norepinephrinergic nucleus, locus ceruleus (LC), is thought to
participate in modulation of such brain areas as cerebral cortex, septum,
hippocampus, thalamus, hypothalamus, and cerebellum in animals facing various
physiological challenges, including stress. Exposure of experimental animals to
different stressors causes an increase in LC activity and gene expression of
tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine
biosynthesis. The aim of this work was to investigate the effect of a single and
repeated (7 times) or long-term repeated (42 times) daily immobilization stress
(IMMO) on TH mRNA levels in LC of laboratory rats by in situ hybridization
method. A single IMMO caused significant elevation of LC TH mRNA levels in
comparison to unstressed controls. This was found immediately and at 3 and 6 h
after IMMO, and progressively increased up to 24 h after the first IMMO
terminated. Further exposure to IMMO did not cause additional increases in LC TH
mRNA levels, which stayed significantly elevated in comparison to unstressed
rats. In animals that underwent IMMO for 42 times, the LC TH gene expression, 24
h after the last stress exposure, was significantly lower when compared to that
of singly or seven times stressed rats. Thus, our results indicate a possible
adaptation of catecholamine-synthesizing system at the level of TH gene
expression in LC of rats exposed to long-term repeated IMMO.
PMID- 9642678
TI - Effect of phenol on the ion currents of frog nerve ending.
AB - The effect of phenol on the transmitter release was studied at the neuromuscular
junction of a frog cutaneous pectoris muscle using the extracellular
microelectrode technique. It was shown that phenol (0.5 mM) enlarged the quantal
content of the end-plate currents (EPCs), and it caused the increase of duration
of the second negative and third positive phases of the triphasic response
observed experimentally. The amplitude of the third phase (outward K+ current)
decreased, and one of the second phase was unchanged. The effect of phenol
remained in the presence of the Ca(2+)-channel blockers (Co2+, Mn2+), and
disappeared in the presence of the tetraethylammonium (TEA) and 4-aminopyridine
(4-AP). The results suggest that phenol changes the kinetics of the voltage
dependent K+ current, which is one of the mechanisms of the phenol facilitating
effect at the synaptic transmission.
PMID- 9642679
TI - Eleanor Roosevelt Institute.
PMID- 9642680
TI - Establishing a link between oncogenes and tumor angiogenesis.
AB - We have tried to stress that mutant oncogenes or overexpressed, nonmutated proto
oncogenes, in addition to their direct affect on promoting aberrant tumor cell
proliferation (and survival), may possess a crucial indirect means of stimulating
tumor cell growth through regulation of angiogenesis. This effect would never be
observed in tissue culture studies of oncogene function using pure cultures of
tumor cells, which probably helps explain why the pro-angiogenic function of
oncogenes has not been appreciated until only relatively recently. Indeed, the
very first indication of a possible contributory role of oncogenes, such as ras
and myc, to tumor angiogenesis was first reported by Thompson et al. in 1989, who
used reconstituted organ cultures of the mouse prostate gland for their studies
(69). This potentially important contribution of oncogenes to tumor growth and
development may prove to have an impact on how various signal transduction
inhibitors that are now in early phase clinical trials, e.g., monoclonal
neutralizing antibodies to the human EGF receptor (70), function in vivo as anti
tumor agents.
PMID- 9642681
TI - Convergence and divergence of the signaling pathways for insulin and
phosphoinositolglycans.
AB - Phosphoinositolglycan molecules isolated from insulin-sensitive mammalian tissues
have been demonstrated in numerous in vitro studies to exert partial insulin
mimetic activity on glucose and lipid metabolism in insulin-sensitive cells.
However, their ill-defined structures, heterogeneous nature, and limited
availability have prohibited the analysis of the underlying molecular mechanism.
Phosphoinositolglycan-peptide (PIG-P) of defined and homogeneous structure
prepared in large scale from the core glycan of a glycosyl-phosphatidylinositol
anchored membrane protein from Saccharomyces cerevisiae has recently been shown
to stimulate glucose transport as well as a number of glucose-metabolizing
enzymes and pathways to up to 90% (at 2 to 10 microns) of the maximal insulin
effect in isolated rat adipocytes, cardiomyocytes, and diaphragms (G. Muller et
al., 1997, Endocrinology 138: 3459-3476). Consequently, we used this PIG-P for
the present study in which we compare its intracellular signaling with that of
insulin. The activation of glucose transport by both PIG-P and insulin in
isolated rat adipocytes and diaphragms was found to require stimulation of
phosphatidylinositol (PI) 3-kinase but to be independent of functional
p70S6kinase and mitogen-activated protein kinase. The increase in glycerol-3
phosphate acyltransferase activity in rat adipocytes in response to PIG-P and
insulin was dependent on both PI 3-kinase and p70S6kinase. This suggest that the
signaling pathways for PIG-P and insulin to glucose transport and metabolism
converage at the level of PI 3-kinase. A component of the PIG-P signaling pathway
located up-stream of PI 3-kinase was identified by desensitization of isolated
rat adipocytes for PIG-P action by combined treatment with trypsin and NaCl under
conditions that preserved cell viability and the insulin-mimetic activity of
sodium vanadate but completely blunted the insulin response. Incubation of the
cells with either trypsin or NaCl alone was ineffective. The desensitized
adipocytes were reconstituted for stimulation of lipogenesis by PIG-P by addition
of the concentrated trypsin/salt extract. The reconstituted adipocytes exhibited
65-75% of the maximal PIG-P response and similar EC50 values for PIG-P (2 to 5
microns) compared with control cells. A proteinaceous N-ethylmaleimide (NEM)
sensitive component contained in the trypsin/salt extract was demonstrated to
bind in a functional manner to the adipocyte plasma membrane of desensitized
adipocytes via bipolar interactions. An excess of trypsin/salt extract inhibited
PIG-P action in untreated adipocytes in a competitive fashion compatible with a
receptor function for PIG-P of this protein. The presence of the putative PIG-P
receptor protein in detergent-insoluble complexes prepared from isolated rat
adipocytes suggests that caveolae/detergent-insoluble complexes of the plasma
membrane may play a role in insulin-mimetic signaling by PIG-P. Furthermore,
treatment of isolated rat diaphragms and adipocytes with PIG-P as well as with
other agents exerting partially insulin-mimetic activity, such as PI-specific
phospholipase C (PLC) and the sulfonylurea glimepiride, triggered tyrosine
phosphorylation of the caveolar marker protein caveolin, which was apparently
correlated with stimulation of lipogenesis. Strikingly, in adipocytes subjected
to combined trypsin/salt treatment, PIG-P, PI-specific PLC, and glimepiride
failed completely to provoke insulin-mimetic effects. A working model is
presented for a signaling pathway in insulin-sensitive cells used by PIG(-P)
molecules which involves GPI structures, the trypsin/salt- and NEM-sensitive
receptor protein for PIG-P, and additional proteins located in caveolae/detergent
insoluble complexes.
PMID- 9642682
TI - Advanced glycation endproducts in neurofilament conglomeration of motoneurons in
familial and sporadic amyotrophic lateral sclerosis.
AB - BACKGROUND: Massive neurofilament conglomeration in motor neurons has been
described to occur in the early stages of both familial and sporadic amyotrophic
lateral sclerosis (ALS). Previously, neurofilament conglomerates were
immunolabeled for both superoxide dismutase (SOD1) and nitrotyrosine, suggesting
the potential for oxidative nitration damage to neurofilament protein by
peroxynitrite. Long-lived neurofilaments may also undergo modification by
advanced glycation endproducts (AGEs) with concomitant generation of free
radicals, including superoxide. This radical species may then react with nitric
oxide to form the potent oxidant, peroxynitrite, which in turn can nitrate
neurofilament protein. Such a glycated and nitrated neurofilament protein may
become resistant to proteolytic systems, forming high-molecular-weight protein
complexes and cytotoxic, neuronal inclusions. MATERIALS AND METHODS: Paraffin
sections containing both neurofilament conglomerates and neuronal inclusions were
obtained from patients with sporadic (n = 5) and familial (n = 2) ALS and were
probed with specific antibodies directed against the AGEs cypentodine/piperidine
enolone, arginine-lysine imidazole, pentosidine, and pyrraline. RESULTS:
Neurofilament conglomerates, but not neuronal inclusions, were intensely
immunolabeled with each of the anti-AGE antibodies tested. The immunoreactivity
was selective for neurofilament conglomerates and suggested that AGEs may form
inter- or intramolecular cross-links in neurofilament proteins. CONCLUSIONS:
These data support the hypothesis that AGE formation affects neurofilament
proteins in vivo and is associated with the concomitant induction of SODI and
protein nitration in neurofilament conglomerates. AGE formation in neurofilament
protein may not only cause covalent cross-linking but also generate superoxide
and block nitric oxide-mediated responses, thereby perpetuating neuronal toxicity
in patients with ALS.
PMID- 9642683
TI - Multiparameter analysis of clastogenic factors, pro-oxidant cytokines, and
inflammatory markers in HIV-1-infected patients with asymptomatic disease,
opportunistic infections, and malignancies.
AB - HIV-1-infected patients are in chronic oxidative stress and clastogenic factors
(CFs) are present in their plasma. CFs from patients with HIV are formed via
superoxide anion radical and stimulate further superoxide production. The
pathophysiolgic significance and the exact composition of the circulating
clastogenic material in patients with HIV is unknown. Cytokines, such as tumor
necrosis factor-alpha (TNF-alpha), are increased in the plasma of patients with
HIV and TNF-alpha shows clastogenic activity in vitro. The aim of this clinical
study was to compare levels of CF in HIV-1-positive patients with asymptomatic
disease, opportunistic infections, and malignancies with those in HIV-1-negative
control groups and to correlate CF activity with CD4+ T cell numbers, the
cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the inflammatory markers
(C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were
significantly increased in all HIV-1-positive patients and in HIV-1-negative
patients with malignant tumors. HIV-1-positive patients with Kaposi's sarcoma
showed the highest CF activity in their plasma (p < 0.08). CFs appear very early
in HIV infection, and they correlate negatively with CD4+ T cells, which are an
indicator of disease activity. The presence of CF in the plasma of HIV-infected
patients is not a general response to a viral infection because these factors are
not increased in HIV-1-negative patients with viral infection (zoster). CFs are
not specific for the HIV-1 infection; they also occur in HIV-1-negative patients
with malignant tumors. There was a tendency towards a positive correlation (p <
0.14) between CF and TNF-alpha but there was no positive correlation of CF with
IL-2, IL-6, CRP, elastase, and neopterin levels. This indicates that TNF-alpha
may be among the components of CF in HIV-1-infected patients. In addition, other
unidentified components may contribute to the clastogenic activity of the plasma
or the composition of CF may vary from patient to patient. Further clinical
studies with larger sample populations are necessary to analyze the composition
of CF in HIV-1-positive patients.
PMID- 9642684
TI - Requirements for allergen-induced airway hyperreactivity in T and B cell
deficient mice.
AB - BACKGROUND: The pathogenesis of asthma is believed to reflect antigen-induced
airway inflammation leading to the recruitment of eosinophils and activation of
mast cells through cell-associated IgE. Controversies persist however, regarding
the relative importance of different pathogenic cells and effector molecules.
MATERIALS AND METHODS: A variety of gene-targeted mice were examined for the
induction of cholinergic airway hyperresponsiveness (AH), allergic airway
inflammation, mucus production, and serum IgE reactivity following intratracheal
challenge with a potent allergen. AH was determined using whole-body
plethysmography following acetylcholine challenge. Where possible, results were
confirmed using neutralizing antibodies and cell-specific reconstitution of
immune deficient mice. RESULTS: T and B cell-deficient, recombinase-activating
gene-deficient mice (RAG -/-) failed to develop significant allergic inflammation
and AH following allergen challenge. Reconstitution of RAG -/- mice with CD4+ T
cells alone was sufficient to restore allergen-induced AH, allergic inflammation,
and goblet cell hyperplasia, but not IgE reactivity. Sensitized B cell-deficient
mice also developed airway hyperreactivity and lung inflammation comparable to
that of wild-type animals, confirming that antibodies were dispensable. Treatment
with neutralizing anti-IL-4 antibody or sensitization of IL-4-deficient mice
resulted in loss of airway hyperreactivity, whereas treatment with anti-IL-5
antibody or sensitization of IL-5-deficient mice had no effect. CONCLUSIONS: In
mice, CD4+ T cells are alone sufficient to mediate many of the pathognomonic
changes that occur in human asthma by a mechanism dependent upon IL-4, but
independent of IL-5, IgE, or both. Clarification of the role played by CD4+ T
cells is likely to stimulate important therapeutic advances in treatment of
asthma.
PMID- 9642685
TI - Effect of targeted mutation in collagen V alpha 2 gene on development of
cutaneous hyperplasia in tight skin mice.
AB - Collagen V plays a major regulatory role in the formation of heterotypic fibers
of the dermis and cartilaginous tissues as well as in the assembly of
extracellular matrix. The pN/pN mouse, which is defective in collagen V alpha 2
gene, exhibits skeletal abnormalities, skin fragility, and alterations in the
collagen fiber organization, whereas the TSK/+ mouse, which is defective in
fibrillin-1, the major component of microfibrils present in the extracellular
matrix, develops cutaneous hyperplasia and autoimmunity. We have studied the role
of collagen V in the formation of heterotypic collagen fibers in F1 mice, which
are obtained by breeding pN/pN with TSK/+ mice. Our results show that F1 progeny
neither develop cutaneous hyperplasia nor produce anti-topoisomerase I
autoantibodies, unlike TSK/+ mice. The diameter of the collagen fibrils in the
skin is also comparable to that found in control mice. Thus, the phenotypic
changes observed in the TSK mouse could be reversed by genetic complementation
with a collagen V-defective mouse.
PMID- 9642686
TI - [Clinical application of three-dimensional ultrasound imaging as intraoperative
navigation for liver surgery].
AB - Intraoperative hepatic ultrasonography provides a great deal of information about
tumor location and vascular anatomy in the liver, and is an indispensable
procedure for hepatic resection. However, an accurate three-dimensional
understanding of ultrasound (US) images depends on the operator's skill and
experience, as the original display is two dimensional. We developed a new three
dimensional US (3D-US) image processing method by application of the intensity
projection method to US. The minimum and maximum intensity projection can display
the arrangement of blood vessels (hepatic veins and portal veins) and hyperechoic
regions, respectively. The intensity projection from several points of view can
reconstruct 3D imaging by cine-display. Moving a probe manually, images are taken
and processed on a real-time basis (in about 10 seconds). 3D-US was used in 24
patients undergoing hepatic resection, and allowed easy visualization of the
tumors and vascular anatomy. It is considered to be an efficient and safe
navigation system in liver surgery.
PMID- 9642687
TI - [Surgical treatment for hepatocellular carcinoma: liver resection using
transplantation techniques].
AB - Ex situ partial liver resection was performed in 2 patients with hepatocellular
carcinoma (HCC) with Child A-liver cirrhosis that was untreatable by conventional
liver resection techniques. In both cases, an extended left lobectomy was first
performed, and then the autologous lateral segment was transplanted after
removing segment 4 (or + a part of segment 5, 8) together with the tumor by the
bench procedure. Although there might have been no difference in preoperative
liver function in these cases, the postoperative course was quite different. The
first case was successful with an uneventful postoperative course, but, the
second case went into postoperative liver failure and the patient died of
multiple organ failure on the 20th postoperative day. The cause of liver failure
in the second case might be attributable to: 1) prolongation of cold preservation
time for the bench procedure (196 min); or 2) over reduction of the native
remnant liver (right lobe) due to resection of the huge tumor. In conclusion, the
technique using ex situ partial liver resection and transplantation of the
remnant section of the liver might be a useful method to extend surgical
treatment for some cases of HCC untreatable by conventional liver resection.
However, the indications should be carefully considered in each case, since graft
damage can occur rapidly during the bench procedure due to combined liver
cirrhosis.
PMID- 9642688
TI - [Treatment of hepatocellular carcinoma: application of vascular surgery].
AB - The present status of hepatic resection for hepatocellular carcinoma (HCC) is
reviewed with special reference to the vascular aspects. Hepatic resection
combined with portal tumor thrombectomy has been attempted in Japan. This
procedure may be effective in the prevention of rupture of esophageal varices and
making transcatheter arterial embolization possible. According to the report of
Yamaoka and his associates, the 1- and 3-year survival rates of 29 patients
treated with this combined procedure were 53% and 12%, respectively. This
surgical strategy may thus yield survival benefits. In patients with a tumor near
the confluence of the major hepatic vein and inferior vena cava, resection of
segments 4b, 7, and 8 combined with hepatic vein reconstruction has been
performed, which allows functional preservation of the residual liver. The
historical development of hepatic vascular exclusion (HVE) is also reviewed. HVE
can be performed safely using a centrifugal active pump, even in patients with
cirrhosis. Hepatic resection combined with removal of tumor thrombus in the right
atrium has been carried out using extracorporeal circulation. There are reports
that at least two patients undergoing this operation survived more than 2 years
after surgery. The hepatic warm ischemic time should be less than 60 min.
Vascular surgery techniques are being increasingly applied in Japan for the
treatment of HCC. Such surgery can be performed safely even in patients with
cirrhosis. Improvement of long-term survival in patients undergoing such
procedures remains an unresolved problem, however.
PMID- 9642689
TI - [Long-term results after hepatectomy for hepatocellular carcinoma according to
cancer stage].
AB - The survival rates after hepatectomy for hepatocellular carcinoma (HCC) according
to cancer stage were reported. The 5-year survival rates of Stage 1, 2, 3 and 4
were 69.6%, 54.2%, 35.9% and 30.2%, respectively. A significant difference was
observed between any neighboring two stages. But more than 5 years till 20 years,
the survival curves cross at some times. That means after 5 years the influence
of the anatomic condition of the initial cancer has been weak. Probably another
factor which controls multi-centric carcinogenesis of HCC may work. When the
survival rate was calculated dividing the stage group into two sub-groups
according to liver function, with good function or poor function, the survival of
the poor liver function group of any stage group was worse than that of the good
liver function group of the nearest worse stage group. The survival after
hepatectomy of HCC depends not only upon anatomic condition of the cancer but
also upon the liver function.
PMID- 9642690
TI - [Topical cooling as an adjunct for hepatectomy with inflow occlusion].
AB - Hypothermia of the liver was developed to alleviate the ischemic insult induced
by prolonged hepatic inflow occlusion. The use of hypothermia in liver surgery
dates back to an experiment in 1953, which showed that the safe normothermic
ischemic time of 20 minutes could be prolonged to 60 minutes with generalized
cooling. Generalized cooling was first used clinically as an adjunct to
hepatectomy with inflow occlusion in 1961. This method has not been widely used
due to its adverse effect on systemic hemodynamics. Subsequently, methods of
inducing hypothermia evolved to encompass in situ isolated hypothermic perfusion
under total vascular exclusion, and then to hemihepatic hypothermic perfusion
without the need for total vascular exclusion but with topical surface cooling.
These technically feasible modifications were newly devised by our group. Our
series of 39 hepatectomized patients, who underwent right-sided hepatectomy under
hemihepatic inflow occlusion combined with topical surface cooling (October 1990
to April 1997), demonstrated that even in livers associated with chronic liver
disease, if surface topical cooling was interposed, a consecutive hemihepatic
inflow occlusion time of as long as 60 +/- 23 minutes was acceptable without
cyclic recirculation. In addition, no further ischemic insult occurred compared
with a normothermic patient series with a significantly shorter occlusion time.
Our data lead to the conclusion that the topical surface cooling method can be a
useful and feasible adjunct to complicated hepatectomy in which inflow occlusion
time is anticipated to prolong.
PMID- 9642691
TI - [Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma].
AB - Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma (HCC) is
discussed. There is a high recurrence rate of HCC of up to 50% or more within
three years after hepatectomy. More than 80% of those recurrences are in the form
of intrahepatic metastases. Therefore it is extremely important to administer
successful adjuvant therapy to prevent intrahepatic recurrence. There are two
types of intrahepatic recurrence: simple dissemination from the primary focus of
HCC; and newly developed HCC in the remnant liver. TAE is one option for
preoperative adjuvant therapy to prevent intrahepatic recurrence. Postoperative
adjuvant chemotherapy via the hepatic artery has occasionally been administered,
but it is not yet established as an effective adjuvant therapy. However, a report
by Muto et al showed that retinoid administration can prevent intrahepatic
recurrence of newly developed HCC after hepatectomy. On the other hand, adjuvant
therapy must not be tooaggressive, because: 1) HCC develops mainly in cirrhotic
liver (with poor liver function); and 2) locoregional therapy for intrahepatic
recurrence results in good survival rats even after detection of an established
recurrence.
PMID- 9642692
TI - [Percutaneous transhepatic portal vein embolization for hepatocellular
carcinoma].
AB - We report on the significance of percutaneous transhepatic portal vein
embolization (PTPE) for hepatocellular carcinoma based on the results in 111
patients who underwent PTPE in our hospital. All patients tolerated the procedure
without major complications, although transient elevations in serum transaminase
levels were noted. Immediately after PTPE, the portal pressure increased. Portal
venous flow at the main portal trunk decreased, but the flow in the nonembolized
part of the liver increased. PTPE produced regenerative hypertrophy in the
nonembolized part of the liver, which was mainly predicted by the volume of the
embolized area and the morphological score of the hepatitis or cirrhosis. PTPE
increased the safety of subsequent hepatectomy and expanded the indications for
hepatectomy. PTPE is also useful as a type of multiplicative therapy for
hepatocellular carcinoma.
PMID- 9642693
TI - [Systematic resection for hepatocellular carcinoma].
AB - We have performed systematic subsegmentectomy in patients with hepatocellular
carcinoma complicated mainly by cirrhosis. Such small anatomical resections have
become possible due to the introduction of intraoperative ultrasonography and of
vascular occlusion techniques. As a result of our clinical experience involving
163 cases, it has been clarified that subsegmentectomy is a safe procedure
(operative mortality rate, 0.6%) and results in a favorable long-term outcome (5
year survival rate, 51%). In the resected specimens, microscopic cancer spread
was recognized frequently (portal venous invasion, 41%; intrahepatic metastasis,
31%). Subsegmentectomy is therefore the first procedure of choice in patients who
have small hepatocellular carcinoma and chronic hepatitis or cirrhosis.
PMID- 9642694
TI - [Hepatic resection using glissonean pedicle transection].
AB - The basics of hepatic resection using the glissonean pedicle transection method
are presented. The portal triad continues from the hepatoduodenal ligament to the
intrahepatic portion in the from of the glissonean pedicle, i.e., the artery,
portal vein, and bile duct are Combined with connective tissue and sheathed by
the peritoneum in the form of a fibroid bundle. The full length of the primary
branches and the origin of secondary branches are located extrahepatically, and
the trunk of the secondary and more peripheral branches have an intrahepatic
course. The ramification pattern of the tertiary branches of each secondary
branch varies by individual. The liver is nourished by the 3 secondary branches
of the glissonean pedicle. Each secondary branch supplies one segment, and
therefore the liver can be divided into 3 segments and the additional caudate
area. The area supplied by each of the tertiary branches is cone shaped ("cone
unit"). Each segment is composed of from 6 to 8 cone units. The standard method
for hepatic resection is the segmental resection method, in which one secondary
branch is transected. In cases of limited resection, the number of cone units to
be resected is adjusted, and the tertiary branches which supply them must also be
transected selectively through the hilar or parenchymal approach. The author has
performed hepatic resection using the glissonean pedicle transection method in
834 consecutive patients with hepatocellular carcinoma with no trouble.
PMID- 9642695
TI - [Xenotransplantation research for clinical practice].
AB - In Japan a very strict brain death transplant bill has been effective since
October 1997. However, the number of potential heart donors will be very few. In
the United States and Europe, where most organ transplants are carried out, the
chronic donor organ shortage has increased interest in the possible use of
xenogeneic organs for transplantation in humans. Pigs, which are possible donors,
now appear to be incompatible with humans and their organs will be hyperacutely
rejected. The mechanism of hyperacute rejection is now well elucidated with
clarification of the roles of complement and xenogeneic antigen. The strategies
for overcoming hyperacute rejection involve creating transgenic pigs with
insertion of human anti-complement genes and modification of their xenoantigens.
The Japanese Society for Xenotransplantation has recently been established, ant
the 5th International Congress for Xenotransplantation will be held in Nagoya in
October 1999.
PMID- 9642696
TI - [N-3 polyunsaturated fatty acids in surgical nutrition].
AB - Recent surgical nutrition includes the management of mediator to induce the
stress response and immune function. N-3 polyunsaturated fatty acid (n-3 PUFA)
were reported to increase the survival rate, and to improve the nutritional and
immune status of septic or burned animals. N-3 PUFA also inhibited the
proliferation and metastasis of cancer, and improved the cancer cachexia. N-3
PUFA decreased the production of cytokine and eicosanoid originated from n-6
PUFA, and reduced the inflammatory and stress response. Cell-mediated immunity
was suppressed with the reduction of cytokine. But in the stressed state, N-3
PUFA ameliorated the stress induced immunosuppression. Alteration of
transcription of cytokine mRNA, changes of membrane fluidity, and reduced
expression of adhesion molecule were proposed to interpret these effects. In
conclusion, n-3 PUFA can be applied for the surgical patients, especially for the
critically ill patients.
PMID- 9642697
TI - [A case of primary squamous cell lung cancer invading the wall of the distal
aortic arch and the left subclavian artery: successful surgical management using
ECC with selective cerebral perfusion].
AB - A 37-year-old male was referred to our hospital with symptoms suggesting
pneumonia. The preoperative diagnosis was primary lung cancer of the left upper
lobe invading the distal aortic arch (DAA) (T4, stage IIIB). Complete resection
was performed with associated resection of the pneumonectomy, DAA, and left
subclavian artery. Dacron graft replacement was performed using ECC with
selective cerebral perfusion. Histological examination revealed squamous cell
carcinoma, n1 and negative surgical margins. We expect this patient to achieve
long-term survival. We conclude that ECC with selective cerebral perfusion is
both safe and effective for pulmonary surgery in cases with combined resection of
the DAA.
PMID- 9642698
TI - [A resected case of so-called carcinosarcoma of the lung which was diagnosed as
diaphragmatic tumor].
AB - A 64-year-old male complained of right hypochondralgia and was admitted to our
hospital. A large tumor (10 x 15 x 10 cm) of the right diaphragm was detected
involving the middle and lower lobe of the lung. Microscopic and
immunohistochemical examinations showed that bronchiolo-alveolar cell carcinoma
was interposed in the sarcoma-like lesion, and this tumor was diagnosed as a so
called carcinosarcoma of the lung.
PMID- 9642699
TI - Can we have it both ways?
PMID- 9642700
TI - Capitated reimbursement for medical services returns control of the patient to
the surgeon.
AB - Limiting the spending on healthcare services is a societal necessity, whether
externally budget-driven with reduced fee for service or salary, or internally
controlled through prospective payment capitation. No reimbursement system is
inherently good or bad. Ethical physicians will place patient well-being first
and focus on the delivery of quality care, regardless of the payment method.
There are several methods for the distribution of capitation payments to
physicians, each with different levels of financial incentive to provide
services. In one fully evolved embodiment of capitation, a payer carves out the
entire orthopedic disease segment and contracts with an orthopedic organization
for all musculoskeletal services within a defined geographic region. This form of
capitation offers the advantage of returning control of patient care to the
orthopedic surgeon.
PMID- 9642701
TI - Capitation of specialty care is complex.
PMID- 9642702
TI - Treatment of humeral fractures by closed reduction and retrograde intramedullary
Ender nails.
AB - A retrospective review of 94 humeral shaft fractures stabilized with retrograde
Ender nails was performed to determine the safety and efficacy of this technique.
Follow-up averaged 71 weeks. Eighty-six (91.5%) healed with no additional
intervention (average: 14 weeks). There were eight (8.5%) nonunions. The
functional results were good in 74 (81%), fair in 12 (13%), and poor in 5 (6%).
There was one radial nerve palsy secondary to the operative procedure. The
reoperation rate, including the repair of nonunions, was 19%. We conclude that
intramedullary Ender nail fixation is a relatively simple and quick procedure,
especially for the multiply injured patient, that adequately stabilizes most
humeral fractures, yielding overall good results.
PMID- 9642703
TI - Follow-up of intertrochanteric osteotomy of the hip during a 25-year period.
AB - In 1984, in reporting follow-up on 67 hips in 61 patients who underwent
intertrochanteric osteotomies for osteoarthritis of the hip, we found that
between 12 and 15 years after osteotomy, 34% (23) of the 67 hips remained
functional and the remainder had been converted to an arthroplasty. We now report
on the fate of those osteotomies over a 25-year period. Ten patients with 10
osteotomies did not require an arthroplasty, having died without requiring
conversion to total hip arthroplasty at an average of 18.3 years after osteotomy
(range: 11 to 24.1 years). Two others were living at an average of 25.2 years
after osteotomy without requiring conversion. Thus, for 18% of the hips, no
further hip surgery was performed. For the remaining 55 hips in 49 patients, the
osteotomy had served for an average of 9.8 years (range: 1.3 to 26.1 years)
before requiring arthroplasty. The cumulative probability of osteotomy survival
was 57.8% (standard error: 6.0%) at 10 years, 20.0% (standard error: 4.9%) at 20
years, and 5.7% (standard error: 2.9%) at 25 years by Kaplan-Meier survivorship
analysis.
PMID- 9642704
TI - ACL reconstruction in children with open physes.
AB - Nine male patients with wide open physes who underwent intra-articular anterior
cruciate ligament (ACL) reconstruction using semitendinosus and gracilis tendon
grafts passed through the tibial physis and over the top of the femoral condyles
were retrospectively reviewed at an average follow-up of 39 months (range: 24 to
72 months). Five patients underwent reconstruction < 6 weeks following injury
(range: 11 days to 41 days); the other four underwent reconstruction 2, 3, 5, and
24 months following injury. Seven patients had excellent results and fully
returned to their sport. Mean Lysholm score in these patients was 99 (range: 95
to 100), and the mean maximum KT-1000 difference (available for six patients) was
2.8 mm (range: 0 to 5.5 mm). Four of six intact grafts had a mean maximum KT-1000
difference < or = 3.5 mm. Two grafts ruptured and were considered failures (one
complete rupture at 10 months and one partial rupture at 3 years). Postoperative
height increase averaged 10.7 cm (range: 4 to 22.9 cm). No patient had a
clinically significant leg-length discrepancy, angular deformity, or radiographic
evidence of physeal injury.
PMID- 9642705
TI - Long-term results of the operative treatment of clubfoot: a representative study.
AB - This study reports the long-term results of operative treatment of clubfoot. Of
the patients who underwent posteromedial release for congenital clubfoot between
1972 and 1975 at the Medical University in Pecs, Hungary, 41 feet of 30 patients
have been under control examination. Control consisted of the distribution of
questionnaires, physical examination, and in some cases, radiologic analysis. At
an average of 20 years postsurgery, good clinical results were observed in 31
(75%) feet. In these patients, satisfying foot form and good function were
achieved, yet the characteristic atrophy of the calf and shortening of the foot
were visible. Abnormal conditions were found in 10 feet, consisting of
overcorrection in 6 and undercorrection in 4 cases. Subjective judgment of the
patients was considerably better; only 5 (12%) feet had no satisfying results.
Data of feet in an incorrect position were analyzed and compared with other
cases. In cases of feet operated on in patients aged > or = 1 year and in
patients who underwent multiple operations, abnormalities were found in a
significantly higher percentage.
PMID- 9642706
TI - A simple outpatient test for proprioception in the anterior cruciate ligament
deficient knee.
AB - Proprioception was quantified in 32 patients who had an arthroscopically
documented complete anterior cruciate ligament tear using a simple single-limb
standing test. An age-matched control group underwent identical testing. Control
subjects demonstrated identical values between their two limbs, with the mean
variation being 4.8%. The test group, however, showed significantly higher mean
values for the injured compared with the noninjured limb, the mean variation
being 43.8%. Patients who have a complete tear of the anterior cruciate ligament
may experience a decline in proprioceptive function of their knees. This can be
tested clinically using a simple single-limb standing test in an outpatient
setting.
PMID- 9642707
TI - C-reactive protein in orthopedics.
PMID- 9642708
TI - Polymethylmethacrylate removal from the femur using a crescentic window
technique.
AB - This article describes a technique to aid in removal of polymethylmethacrylate
during total hip arthroplasty revision. The technique is a modification of prior
windowing techniques and requires no specialized instruments, offers substantial
flexibility regarding cement removal and femoral prosthetic choice, and minimizes
the amount and duration of stress on the femur. The technique involves making an
oblong window in the anterior or anterolateral femur. Proximal and distal
osteotomies are made with a crescentic oscillating saw and connected by straight
beveled anterior and posterior longitudinal osteotomies using a straight
oscillating saw. Once the intramedullary canal is prepared, either a nonecmented
or cemented femoral prosthesis can be placed. The cortical window is replaced
with a single cable used for fixation.
PMID- 9642709
TI - Location of the sacral pedicle, foramina, and ala on the lateral aspect of the
sacrum: a radiographic study.
AB - Twenty-one adult dry-bone sacral specimens were used to quantitatively determine
the location of the sacral pedicle, foramina, and ala on the lateral radiographic
view of the sacrum. The anterior and posterior sacral foramina from S1 to S3, the
midlines of the anterior sacrum and cephalad border of the S1 vertebral body, and
the lateral limit of the lateral sacral mass were outlined with wires. A lateral
radiograph was taken, and measurements were made directly from the radiograph.
The average sacral pedicle height for both male and female specimens was
approximately 20 mm for S1, 12 mm for S2, and 7 mm for S3. The sacral foramina
height averaged approximately 13 mm for S1 and S2, and 10 mm for S3. The average
ala and S1 body-ala angles were 88 degrees and 35 degrees. The distance from the
ala tip to the anterior aspect of the sacrum averaged 12 mm, and the average
anterior height of the S1 vertebral body above the ala was 11 mm. These
measurements, in conjunction with inlet and outlet radiographs, may aid in the
recognition of the vital structures of the sacrum on the lateral radiographic
view and enhance the safety of dorsal sacral screw placement.
PMID- 9642710
TI - Total hip arthroplasty in patients with low-lumbar-level myelomeningocele.
PMID- 9642711
TI - Fracture of the fabella: a case of posterolateral knee pain.
PMID- 9642712
TI - Diskitis caused by Actinobacillus actinomycetemcomitans.
PMID- 9642713
TI - Bilateral osteochondritis dissecans of the knee and elbow.
PMID- 9642714
TI - Radiologic case study. Reflex sympathetic dystrophy.
PMID- 9642715
TI - [Women and health].
PMID- 9642716
TI - [Women and health in numbers. Puerto Rico, 1994].
AB - The purpose of this study was to explore the health situation of women in Puerto
Rico through the analysis of the causes of deaths in medical certification
contained in death certificates. The data source used was the computer tape
containing the data on deaths occurred in Puerto Rico during 1994. This tape was
produced by the Puerto Rico Department of Health. The analysis of the main causes
of deaths in women showed a trend associated with chronic and degenerative
diseases. This trend is compatible with the one found in women over 65 years old.
In women under 65 years of age, this trend was also observed, although other
causes were also relevant, like deaths by external causes and AIDS. For the age
groups of under 15, 15 to 44, 45 to 64 and 65 and over, the principal causes of
deaths were: conditions related to the perinatal period, AIDS, cancer and heart
and heart related diseases respectively. The degree of vulnerability to death
from certain causes of mortality which changes in importance from one age range
to another in the female population of Puerto Rico is shown by the results of
this research project.
PMID- 9642717
TI - [Legal secrecy: abortion in Puerto Rico from 1937 to 1970].
AB - The essay discusses abortion in Puerto Rico from 1937 to 1970, concentrating in
its legal status as well as its social practice. The research documents the
contradictions between the legality of the procedure and a social practice
characterized by secrecy. The essay discusses the role of the Clergy Consultation
Service on Abortion in promoting the legal practice of absortion in Puerto Rico.
It also discusses the ambivalent role of medical doctors who, despite being
legally authorized to perform abortions to protect the life and health of women,
refused to perform the procedure arguing abortion was illegal. The essay
concludes with a brief discussion on perceptions of illegality regarding
abortion, emphasizing the contradictions between the practice of abortion and
that of sterilization in Puerto Rico.
PMID- 9642718
TI - Abortion in Puerto Rico: the limits of a colonial legality.
AB - This paper situates the current abortion practice and policy in Puerto Rico
within the historical, political, and economic context of the colonial domination
of the United States (US) over Puerto Rico. In particular, we pay attention to
the hurdles that women face to obtain abortion services in Puerto Rico as a
result of its colonial legality. Of particular significance is the overall low
abortion ratio, and differential abortion ratio and access issues faced by women
when grouped by an age-ethnicity category: unmarried teenagers, adult Puerto
Rican women and, adult immigrant women from the Dominican Republic. The present
hurdles to abortion access--related to information, abortion providers, economic
situation, and government policies--are discussed within the colonial legality of
abortion based on the US Supreme Court decision Roe v. Wade. Puerto Rico's case
is situated within its broader history of population policies developed by the
State since the 1930's. Of particular relevance is the antagonism that State
managers have had towards abortion in spite of its legality. In this sense,
abortion in Puerto Rico continues to be an unfinished business, in spite of its
legality.
PMID- 9642719
TI - [Women and health professions in Puerto Rico: 1990].
AB - The main aim of the present study was to analyse the sex distribucion for the
health related professions in Puerto Rico. This was a descriptive investigation.
The data was obtained from the Census of Population and Housing of Puerto Rico,
1990 and the fifth register of health professionals, 1989-92 from the Health
Department of Puerto Rico. It was observed that women in the 90's are still
participating, in the health professions, in occupations traditionally of their
gender. Nevertheless, it has been observed an increased in the women's
participation in those occupations usually performed by men such as: veterinary
and podiatry. Women tend to be employed more frequently by the government. Men,
on the other hand, are concentrated on those occupations with the highest
prestige and status, in the health professions. In addition, a high proportion of
men are employed on their own. In terms of income, women earn less income than
men for almost all the health occupations taken into account.
PMID- 9642720
TI - [To the northernmost part of the airlift bridge: the Puerto Ricans in the United
States].
AB - This article examines the available data on the health status of Puerto Rican
women in the United States. Statistics on reproductive health, cancer and AIDS
indicate that the health status of these women is lower than that of both their
U.S. and island counterparts. Usually, the health of immigrants lies somewhere
between that of the population of the country of origin, and that of the 'host'
country. Puerto Rican women, however, deviate from this pattern. The health lag
which U.S. Puerto Rican women are experiencing suggests that the social
dislocation which accompanies migration has not diminished over time. Puerto
Rican women in the U.S., on the contrary, seem to have lost protective factors
that shielded them from certain risks without acquiring the monetary,
psycological, and information resources which would allow them to adopt
preventive measures and make a more effective use of the existing health
services.
PMID- 9642721
TI - [Feminization of old age in Puerto Rico].
AB - As a result of the inequality of gender in life expectancy, there is a higher
proportion of women than men in old age. The problems and changes that take place
in this stage of life are basically women' problems so it can be stated that
aging is a women's issue. Women face prejudices nor only for being women but also
for being old, sexist and ageist prejudices. This article discusses areas in
which women are affected as they aged such as: discrimination and ageism, poverty
and loneliness, physical and social losses and changes. It will also present the
positive aspects of being old and female.
PMID- 9642722
TI - [Medical negligence in Puerto Rico: 1990-1996].
AB - The purpose of this communication is to present the statistical information of
the medical and hospital professional liability situation in Puerto Rico from
1990 to 1996. The Medical Institutional liability is a topic of great relevancy
and importance to the people of Puerto Rico and the leaders responsible for
establishing policies for the health care services. The Reports on Medical and
Hospital Professional Liability from 1991 to the 1996 produced by the Examining
Physicians Board were reviewed. The liability claims from 1991 to the 1996
totaled 4054. During the seven years analyzed, 3506 cases were closed against
physicians and institutions, a payment was issued in 1272 cases (36.3%), for a
total compensation of $56,268,053. The risk of a legal claim is greater for the
group of Plastic Surgeons and Emergency Medicine. The probability of a plaintiff
receiving a compensation payment in a case of medical malpractice is
approximately 36%, usually receiving a third of the total of the award as
suggested by the medical literature. A thoughtful analysis of the current medical
liability situation and defensive medicine should be done with the purpose of
protecting the fiduciary function of the physicians with respect to the health of
their patients, this is the function that guarantees a physician-patient
relationship that is healthy, righteous and empathic.
PMID- 9642723
TI - [Analysis of survival of patients with end-stage renal disease in Puerto Rico,
1970-1994].
AB - To assess the survival probabilities of patients with end stage renal disease in
Puerto Rico, the data from the United States Renal Data System from 1970 through
1994 was analyzed. The Kaplan Meier method was used to determine the survival
rate for the following variables: diagnosis, gender, age groups, treatment
modality and health regions. The analysis included 7,527 patients reported to the
United States Renal Disease System of which 4,295 (57%) patients were reported
dead. The median time of survival rate (50%) was 47.7 months. There was
significantly lower survival rate (p = 0.0001) for diabetics compared with all
the other diagnosis. Age was also a strong predictor of survival (p = 0.0001) and
modality treatment (p = 0.0001). We concluded that diabetes, the elderly and the
hemodialysis modality, had the lower survival rate in the puerto rican
population.
PMID- 9642724
TI - [Use of health education services for persons living with HIV/AIDS patients in
Puerto Rico: 1994-1995].
PMID- 9642725
TI - A short history of electrophysiology and its techniques. Section III.
Electrophysiological instruments and techniques.
PMID- 9642726
TI - [Health-related quality of life: important result of cancer treatments].
AB - Health related quality of life is an integral part of the outcomes of cancer
treatment. The purpose of this manuscript is to describe the concept of quality
of life of cancer patients, and to summarize the validation studies of the
"Functional Assessment Cancer Therapy Scales" (FACT) in Hispanics. Results of the
studies support the validity of the scale which has the following dimensions:
physical well-being, social/family well-being, relationship with doctor,
emotional well-being, and functional well-being. The validation work makes
possible the assessment of quality of life in Hispanics. Clinical trials which
assess health related quality of life as a treatment outcome provide baseline
information for decision making in the financing of oncology treatments.
PMID- 9642727
TI - [Medical humanities. Health communication contribution to clinical bioethics].
PMID- 9642728
TI - [Lyme disease in Tunisia, results of a clinical and serological study (1992
1996)].
AB - Lyme disease was suspected in 271 patients seeking hospital care between 1992 and
1996. The sera of all these patients were tested by ELISA for antibodies against
Borrelia burgdorferi. Twenty-nine cases of Lyme disease were identified, each
involving neurological and articular problems. These results demonstrate that
Lyme disease occurs in Tunisia and suggest that this diagnosis should be
considered more frequently in patients presenting with the characteristic
symptoms.
PMID- 9642729
TI - [Food habits outside the home by school children in Cotonou (Benin)].
AB - Urban growth leads to the consumption of food outside the home, with the demand
for street food coming particularly from school children. A survey of 240 primary
school children aged 8 to 13 was carried out, by means of personal interviews.
More than 90% were regularly given pocket money by their parents, and this money
was used mainly for buying food from vendors inside or near their schools. Less
than 20% of children ate breakfast at home before going to school. Food purchases
occurred mostly before the end of school morning break and an average of 38 CFA
Francs were spent on each purchase (7.6 US cents). A wide variety of foods were
bought, mostly including cereals. This buying of food seems to be part of a
family food strategy to reduce the preparation of breakfast at home. The
combination of this demand, and the supply of food in schools provides a useful
means for campaigns aimed at improving the quality of children's diets in the
short and long term.
PMID- 9642730
TI - [Cardiovascular risk factors: smoking in the context of recent events in
Lebanon].
AB - Epidemiological studies have demonstrated that cigarette smoking increases the
incidence of myocardial infarction and sudden death. Psychological and physical
stress, like smoking, activates the sympathetic adrenal medullary and pituitary
adrenal cortical systems. We therefore thought that the effects of stress and
smoking together might increase the risk of cardiovascular disease. The seventeen
year Lebanese war was a source of real psychological stress. It was a very
traumatic time for many citizens, forced to cope with the situation and its
tragic consequences. We evaluated the effects of smoking and traumatic
experiences during war using a study population of 46 Lebanese men aged between
28 and 45. We determined hemodynamic characteristics, such as heart rate and
arterial blood pressure, and plasma indicators (cortisol and thromboxane
concentrations). We found that smoking itself significantly increased all of
these variables. The increase was larger, but not significantly so, in smokers
who had experienced traumatic events during the war. This study suggests that
preventive efforts should be directed at those groups with combinations of risk
factors (e.g. smoking and stress) rather than at groups with one risk factor
only. Accurate assessment of risk factors, their predictive value and their
interactions are vital for any program of preventive measures.
PMID- 9642731
TI - [Viral hepatitis A: when a changing epidemiology implies a different
prophylaxis].
AB - Major progress has been made in the epidemiology and prophylaxis of hepatitis A
virus (HAV) since it was first discovered in stool samples by MacCallum in 1973.
Seven types of the virus have been described. Types 1, 2, 3 and 7 occur in humans
and types 4, 5 and 6 in monkeys, but genotype is not correlated with antigenic
response. Immunization with the HM175 viral strain or natural infection by any of
the virus types gives protection against all types of HAV affecting humans.
Serological tests detect all types of the virus and make it possible to carry out
epidemiological studies anywhere in the world. HAV is common in very young
children in developing countries. Most ten-year-old children are immune and have
no clinical signs of the illness. HAV infection has become less common in
developed countries due to improvements in hygiene. Less than 40% of people under
the age of 30 have been immunized. Non-immune individuals have a high risk of
developing clinical hepatitis if they become infected and the older the patient
at the time of infection, the more severe the disease is likely to be. The
introduction of HAV into groups in which the majority of individuals have not
been immunized may result in major local outbreaks. Prophylaxis schemes are
developed on the basis of epidemiology. Vaccination is not routinely recommended
in developing countries, except for visitors to those countries. Vaccination is
recommended for individuals in high-risk groups, such as health workers, cooks,
sewer maintenance engineers and tourists, in developed countries. In countries
with an intermediate level of risk (East Europe, the Middle East and Southeast
Asia), there is a high level of HAV infection and a low level of immunization.
Vaccination programs are likely to be of value in these countries.
PMID- 9642732
TI - [Validation of an evaluation guide for healthcare training programs in the field
of humanitarian efforts].
AB - The training of healthcare professionals working in the field of humanitarian
action is of fundamental importance but there have been few procedures for
assessing the training programs. A specific guide was produced for the evaluation
of healthcare training programs. It uses a three-pronged approach to improve the
training of healthcare personnel, encouraging educators to take a fresh look at
the way in which they work. The guide seeks to improve the efficiency of training
by evaluating programs. The guide was tested on four training programs conducted
by three non-governmental organizations in three countries: Handicap
International in Cambodia and Mozambique, Medecins Sans Frontieres in Cambodia
and Action Nord Sud in Brazil. Questionnaires, guides and appraisals were
analyzed, and the results suggested that the guide was valid, reproducible and
easy to use. However, it is vital to provide external educational assistance
during evaluation, to promote the implementation of decisions, thereby improving
training practices.
PMID- 9642733
TI - [Activities of the African Institute of Tropical Ophthalmology, 1990-1997].
AB - The African Institute of Tropical Ophthalmology (AITO) was founded in Bamako in
1953. It is part of a regional structure, The Organization for Cooperation and
Coordination in the Control of Major Endemic Diseases (OCCCMED). AITO is a WHO
collaborating center for the prevention of blindness and has four aims: the
provision of eye care, training (ophthalmologists, cataract surgeons, specialist
nurses, spectacle manufacturers), research (epidemiology, clinical and surgical)
and assessment of public eye care as a function of the needs of the member states
of OCCCMED. The European Regional Program for the Prevention of Blindness and an
International Sight First Program Center are located at AITO. AITO is at the
heart of a network dedicated to fighting blindness, and its activities extend
beyond the borders of the OCCCMED.
PMID- 9642734
TI - [Health care activities at the African Institute of Tropical Ophthalmology].
PMID- 9642735
TI - [Training at the African Institute of Tropical Ophthalmology in Bamako].
AB - The African Institute of Tropical Ophthalmology (AITO) is an OCCCMED institute,
founded in Bamako in 1953. The OCCCMED itself is based at Bobo Dioulasso (Burkina
Faso). AITO is a WHO collaborating center for the prevention of blindness.
Training is one of the main activities of the institute, along with eye care,
research and assessment. The prevalence of blindness in sub-Saharan countries is
about 1.2%, with blindness mostly caused by cataracts, trachoma, glaucoma and
onchocercosis. The demand for eye care is high but there are currently too few
trained personnel to satisfy that demand. Therefore, AITO's role in training eye
care professionals is particularly important. The institute trains
ophthalmologists, specialist nurses, eye surgeons (who remove cataracts) and
spectacle manufacturers. Training is carried out within the framework of the
community and apprenticeship in the workplace. The student must attain specific
targets, listed in a "competency passport" issued at the start of training.
Clinical and surgical ophthalmology and general eye care are taught. Training
costs and grants are mostly paid by the Lions Club International Sight First
Program or by the French Overseas Development Ministry. Since 1991, AITO has
trained to graduation: 18 ophthalmologists; 24 eye surgeons; 83 specialist
nurses; 16 spectacle manufacturers.
PMID- 9642736
TI - [Future of ophthalmology nurses and physicians trained at the African Institute
of Tropical Ophthalmology].
AB - Six ophthalmologists and 24 specialist ophthalmology nurses from French-speaking
African countries graduate from AITO each year. Their training focuses on the
skills they will need to participate in the national programs to combat
blindness. All the ophthalmologists (10) and specialist ophthalmology nurses (42)
from Mali, Niger, Burkina Faso and Senegal, who graduated from AITO within the
last ten years were interviewed. Eight of the ten ophthalmologists and all of the
specialist nurses are currently working in national programs to combat blindness.
The specialist nurses knew more about public eye health issues than about optics.
The training given is appropriate for ophthalmology professionals working in
these countries. The chief demand of both ophthalmologists and specialist nurses
was that they should have continuous training and supervision.
PMID- 9642737
TI - [Research at the African Institute of Tropical Ophthalmology].
AB - Research is one of the four main activities of AITO. It is vital for the
determination of health care priorities, and for the design, implementation, and
evaluation of programs and projects in OCCCMED countries. Most of the research is
surgical and focused on the diseases which cause blindness. Cataracts are the
principal cause of blindness and have been the focus of many studies aimed at
making surgery more accessible in terms of both geographical availability and
cost. Trachoma is a major public health priority in the countries of the Sahel
and a survey of its prevalence is underway in several countries. This study
should lead to the development of preventive and curative treatments aimed at
controlling blindness caused by trachoma by the year, 2020. Vitamin A deficiency,
the cause of xerophthalmia and high mortality rates in infants, has been surveyed
in several countries. A survey of glaucoma, another major cause of blindness
which is often not recognized or treated, will be carried out in Bamako. Other
studies focus on leprosy, malaria and the effects of visual disability on the
quality of everyday life. It will be a major challenge over the next five years
to develop the capacity within local populations to identify, design and
implement research programs in community health aspects of ophthalmology that
will take into account the needs and constraints of sub-Saharan Africa.
PMID- 9642738
TI - [Synthesis of the blindness situation in the countries of the Organization for
Cooperation and Coordination in the Control of Major Endemic Diseases].
AB - The major causes of blindness in the OCCCMED states are cataracts, trachoma,
glaucoma and oncocercosis. The prevalence of blindness is about 1.2% and there
are about 880,000 blind individuals and 2,500,000 people with impaired vision.
Cataracts were the cause of blindness in 440,000 people and the cause of visual
impairment in 1,320,000 individuals. About 1,500,000 people were found to have
oncocercosis, and about 24,000 were blind. The true rate of trachoma is unknown.
Thirteen thousand cataracts are surgically removed in the region each year, the
CSR (cataract surgery rate) being 210. In the last few years, national programs
have been set up to combat blindness and equipment and training have been
established. With a ratio of 1 ophthalmologist per 523,000 people, the WHO's
objectives are becoming attainable.
PMID- 9642739
TI - [Progress in the control of world blindness and future perspectives].
AB - Worldwide, there are approximately 180 million severely visually impaired people,
of whom some 45 million are blind. Cataract remains the major cause of blindness,
especially in the less developed countries. Substantial improvements have been
achieved in the control of blinding diseases, mainly in respect of onchocerciasis
and xerophthalmia. More recently, a WHO alliance for the eradicating of trachoma
by the year 2020 has been set up. In Africa, the situation remains critical in
spite of significant improvements in the training of eye care personnel and the
implementation of new eye care facilities. If no additional action is taken, the
number of blind from cataract will steadily increase, mainly because of
population growth and aging. Substantial further efforts should be made to make
appropriate eye care accessible and affordable to all those in need.
PMID- 9642740
TI - [Strategies to control cataracts].
AB - Cataracts, often associated with aging (80%), are a major cause of blindness
(more than 50% of cases of blindness in Africa), and for this reason, up to 80%
of cases could be predicted or prevented. The socio-economic costs (care and loss
of productivity) are increased by morbidity (blindness, impaired vision,
congenital, complicated or infected cataracts). The biological determinants of
cataracts account for the difficulties in developing and implementing effective
preventive action. These epidemiological determinants (prevalence, incidence,
increase in life expectancy) account for the size of the public health problem.
The surgical removal of cataracts in Africa currently only deals with about 1% of
the prevalence rate or 10% of the incidence. Cataracts are, however, easy to
cure, resulting in great benefits to public health. The waiting list for cataract
operations is very short because of social and cultural barriers which limit the
acceptability and accessibility of treatment. Rather than formalizing the
dogmatic choices of surgical techniques and structures (fixed, mobile,
advanced?), we should promote all phases of treatment from active screening and
the selection of cases for surgery to the follow-up of interventions and their
impact. We should also increase public awareness, develop a system for the
transfer of information that is effective and improve the cost-effectiveness and
capacity of the region to provide high quality services on a large scale. We must
promote patient satisfaction at all stages of treatment: its quality, its
delivery and its low cost.
PMID- 9642741
TI - [Cataracts, a way into the national health system of Mali?].
AB - Cataracts are common in Mali, where there are 60,000 people awaiting surgery for
blindness caused by cataracts. This major cause of disability in adults could be
used as an effective entry point into the national health system. The development
of an effective referral system should increase the recruitment from districts
and increase the standing of the highest level health centers. Surgery should be
decentralized and carried out at the district level. A specialist surgical team,
based at the regional hospital, would operate with portable equipment in the
district health centers, with patients being referred by peripheral health
centers. The success of this approach depends on the development of strong
functional relationships between peripheral and district health centers and of
interpersonal relationships between the staff members involved. This new approach
should lead to a major reduction in the level of disability whilst strengthening
and promoting the district health system as a whole.
PMID- 9642742
TI - [Strategies to control trachoma].
AB - Epidemiological data for trachoma in Mali have suggested a number of ways in
which blindness caused by trachoma could be prevented or cured: improvements in
domestic and urban environments (e.g. sanitation), the provision of household
water supplies, improvements in personal hygiene (through health education to
promote the washing of children's faces), mass administration of local
(tetracycline) or general (azithromycin) antibiotics and eyelid surgery using the
method of Trabut. A cost-benefit analysis was performed for antibiotic
distribution and eyelid surgery. Such a study is required to assess the value of
environmental improvements and the provision of water supplies. Improvements in
personal hygiene and environment are the only effective ways to reduce the
incidence of trachoma, but eyelid surgery should be developed to prevent the
blindness caused by trachoma.
PMID- 9642743
TI - [Strategies to control glaucoma].
PMID- 9642744
TI - [Strategies to control vitamin A deficiency].
AB - Vitamin A deficiency is a major public health problem in the countries of the
Sahel. It causes xerophthalmia and high rates of child mortality and it occurs
mostly in underdeveloped regions. People of all ages may suffer from vitamin A
deficiency but it is a particular problem in pre-school-age children. Each year,
about 250,000 children throughout the world become blind due to vitamin A
deficiency. Measles, pneumonia and diarrhea reduce the child's reserves of
retinol and increase the dietary requirement for vitamin A. Improvement of social
conditions is a radical approach to preventing vitamin A deficiency. Three
strategies are currently in use: horticultural activities and health education;
fortification of food products; distribution of high-dose vitamin A capsules.
PMID- 9642745
TI - [Contamination of a drinking water distribution network originating in a
toxoplasmosis epidemic].
PMID- 9642746
TI - [Neurosarcoidosis].
AB - Signs and symptoms of neurosarcoidosis are variable and depend on location and
size of granulomas. Clinical studies suggest a rate of 5% and autopsy results a
rate of more than 25% of central nervous system (CNS) involvement in sarcoidosis.
Statistical analysis of 57,789 patients admitted to the Department of Medicine in
Lucerne over an 11-year period revealed 51 patients (0.9/1000) with the diagnosis
of sarcoidosis. Six of these (12%) had sarcoidosis affecting the CNS.
Neurosarcoidosis presented as: leptomeningeal granulomas, cranial nerve palsy,
hypothalamic-pituitary syndrome, diabetes insipidus, pareses, paresthesia,
pyramidal signs, dementia, urine retention, and asymptomatic granulomas.
Neurosarcoidosis has predilections for the base of the brain, cranial nerves
(facial nerve palsy is the most common) and meninges, but any part of the CNS may
be affected. Therefore, the diagnosis of neurosarcoidosis may be extremely
difficult, especially when it occurs as an isolated finding. Positive findings in
transbronchial biopsy and lavage may demonstrate asymptomatic pulmonary
involvement in as many as 50% of patients with neurosarcoidosis. Angiotensin
converting enzyme levels may be raised in the blood or cerebrospinal fluid in
some 50% of cases. Kveim test has a low sensitivity in neurosarcoidosis and thus
is of little use. Gallium uptake may demonstrate extracranial granuloma available
for biopsy. All these tests, and also computed tomography and magnetic resonance
imaging, may be helpful. However, when in selected cases with isolated CNS
disease standard investigations are not conclusive, meningeal or cerebral biopsy
may be required in order to exclude other causes such as other granulomatous
disorders, tumor metastasis, lymphoma, vasculitis, Sjogren syndrome, infection,
neurologic disease such as multiple sclerosis, or systemic diseases such as
Whipple's disease. CNS involvement in the acute phase of the disease has a
favorable prognosis, while chronic courses respond less well to therapy.
Treatment is initiated most frequently with corticosteroids (0.5-1 mg/kg body
weight/day or pulses of 1 g/day of methylprednisolone in severe cases).
Improvement is seen within 1-2 months. Side effects of corticosteroids,
aggressive disease or frequent recurrences may require other immunosuppressive
drugs (methotrexate, azathioprine, chlorambucil, cyclosporine A). Cerebral
irradiation may be successful in some cases when other treatments fail.
PMID- 9642747
TI - [The Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic
excision of mammographically suspect nonpalpable findings in the breast].
AB - Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided
stereotactic excision of non-palpable radiodense lesions with high accuracy.
Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be
removed very accurately under local anaesthesia and on an outpatient basis.
Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and
with round lesions (n = 7) of the breast were qualified for ABBI. We were able to
perform the excisional biopsy in a total of 34 patients. The breast of one woman
was too small to safely fit into the system and in another woman the lesion could
not be visualized by the system. In 2/34 cases (6%), the excision was imprecise
due to slight dislocation of the breast parenchyma by the advancing cylinder
knife. In one case (3%), ABBI missed the target within a dense mastopathic
breast. In all cases the excisions were well tolerated. No wound complications
occurred and the cosmetic result was excellent. Histology revealed 28 benign
(82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there
were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular
hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4
calcifications in scars. Four of the 7 round-shaped lesions were found to be
fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system,
non-palpable breast lesions can be precisely localized and excised.
PMID- 9642748
TI - [X-chromosomal bulbospinal muscular atrophy (Kennedy syndrome)].
AB - Two brothers with slowly progressive weakness and congenital nystagmus are
presented. DNA analysis confirmed X-linked recessive bulbospinal muscular atrophy
(XBSMA, Kennedy's disease) by demonstration of increased size of a CAG-triplet
repeat on the androgen receptor gene on the X-chromosome. XBSMA is characterized
by almost symmetrical muscular atrophy, weakness and fasciculations predominantly
of bulbar, facial and proximal muscles of the extremities, with onset in the
third to fifth decade. Tendon reflexes are depressed and pyramidal signs are
absent. Sensory symptoms are clinically rare, but sensory nerve action potentials
are frequently abnormal. Additional symptoms are important for differential
diagnosis, and include postural tremor, gynecomastia, diabetes mellitus,
testicular atrophy and impotence. Differentiation of this hereditary disorder
from treatable conditions such as multifocal motor neuropathy or amyotrophic
lateral sclerosis is essential. Though life expectancy is normal, patients become
disabled in the course of the disease and need supportive care. Periodic testing
for diabetes is recommended, and genetic counseling should be provided for
patients and their relatives.
PMID- 9642749
TI - [From chondrocyte culture to joint cartilage replacement. Development of de novo
cartilage in vitro].
AB - Local repair of acute or chronic cartilage lesions has not been successful so
far. An attempt has been made to use synthetic materials to improve the quality
of the repair tissue, but no method has achieved reliable regrowth of normal
hyaline cartilage with adequate biomechanical properties and bonding to
surrounding tissue. After publication of the first short-term results of
chondrocyte transplantation in patients with localized cartilage lesions of the
knee joints by a Swedish group in 1994 [1], the situation seems to have changed.
Even though the advantages of this method of chondrocyte transplantation is a
matter of controversy, the interest in the so-called "Carticel" approach has
grown steadily. Indeed, the technique was recently approved by the FDA, on
condition of a randomized, "placebo"-controlled trial. In view of this rapid
development, we feel that independent experimental studies are urgently needed.
In this article we present our own results in synthesizing de novo cartilage from
cultured and phenotypically stable chondrocytes in a truly three-dimensional
cartilage-like polyanionic matrix. With the experience gained in animals, we
expect to set the stage for future experimental therapy in young human patients
with early cartilage lesions.
PMID- 9642750
TI - [Painful discoloration of the forearm].
PMID- 9642751
TI - [Adjuvant therapy of colorectal carcinoma--1998 status].
AB - Colorectal cancer is the second leading cause of cancer death in western
countries. The prognosis is strongly correlated to the TNM-staging system and
patients with stage T3-4 and/or node positive disease are at high risk for
locoregional or distant relapse. It is now widely accepted that patients with
node positive colon cancer should be offered postoperative adjuvant chemotherapy.
Evidence is accumulating that six months' adjuvant fluorouracil plus leucovorin
is equivalent to twelve months' fluorouracil and levamisole, which reduces cancer
related deaths by more than 30%. Other adjuvant treatment approaches are
perioperative regional chemotherapy or monoclonal antibody treatment, and the
results of trials comparing these different treatment options alone or in
combination are eagerly awaited. In rectal cancer, the risk of locoregional
recurrence can be more than 50% and this event is associated with a deterimental
effect on quality of life. The technique of mesorectal excision and the use of
radiotherapy, alone or in combination with chemotherapy, have evolved as the most
important measures for prevention of locoregional recurrence. In addition,
chemotherapy has proven to be effective in reducing metastatic relapse and
prolonging survival. The timing of radiotherapy (pre- versus postoperative) and
the optimal combination of chemotherapy with radiation are presently important
research issues in resected rectal cancer. In both colon and rectal cancer, a
common theme emerging from the experience of the last few decades is that
administration of dose-intensive fluorouracil is key for the success of adjuvant
treatment.
PMID- 9642752
TI - Urinary iodine concentrations in swiss schoolchildren from the Zurich area and
the Engadine valley.
AB - To prevent iodine deficiency disorders in Switzerland, table salt is currently
fortified at 15 mg iodide/kg salt. However, several recent reports have suggested
that urinary iodine excretion is marginal or inadequate among segments of the
Swiss population, including schoolchildren. There is concern that iodine intake
in Switzerland may be approaching levels associated with signs of clinical
deficiency. Previous studies measuring urinary iodine in Swiss children have
encompassed only a limited geographic area in central Switzerland. We have now
evaluated urinary iodine concentrations in 243 schoolchildren aged 5 to 13 years
from the Zurich area and the Engadine valley. The mean urinary iodine for all
children was 11.3 +/- 8.7 micrograms/dl. There was no significant difference
between iodine levels in urine from children in the Engadine and those from
around Zurich. There were also no significant gender differences in urinary
iodine concentrations. The median urinary iodine concentration for all children
was 9.6 micrograms/dl, below the threshold suggested by the World Health
Organization (< 10 micrograms/dl) as indicative of mild iodine deficiency. 54.3%
of the children had urinary iodine concentrations < 10 micrograms/dl and 11.5%
had levels < 5 micrograms/dl. The results of this study suggest that the iodine
status of some Swiss schoolchildren may no longer be adequate. They indicate the
importance of intermittent monitoring of iodine status in Switzerland, where
dietary habits and food supply patterns are changing. They also support the
recent decision (February 1998) by the Swiss Federal Department of the Interior
to increase the concentration of iodide in Swiss table salt, based on the
recommendations of the Fluoride-Iodine Commission of the Swiss Academy of Medical
Sciences.
PMID- 9642753
TI - [What thrombolytic rate can be realized in acute myocardial infarct? Results of
the Oltner Heart Emergency Study].
AB - BACKGROUND: Despite the benefits of thrombolytic therapy, there is evidence that
not all suitable patients are receiving it. Early and accurate recognition of the
ECG changes of myocardial infarction is a prerequisite for effective thrombolytic
treatment. METHODS: During the Olten Heart Emergency Study we prospectively
evaluated 951 consecutive patients with symptoms suggestive of myocardial
infarction who were cared for by the emergency networks connected with Olten
Cantonal Hospital. MAIN OUTCOME MEASURES: The final diagnosis was myocardial
infarction in 173 patients (18.2%). Diagnostic ST-segment elevation was found in
48.6% and complete left bundle branch block in 13.9% of these patients,
representing a total of 62.5% acute myocardial infarction patients eligible for
thrombolysis based on the ECG findings. Using a time limit of 6 hours between
onset of symptoms and hospital entry for small and medium-size myocardial
infarctions and 12 hours for large infarctions, plus an age limit of 70 years for
inferior and 75 years for anterior infarctions as exclusion criteria for
thrombolysis, we found one or more contraindications for the use of thrombolytic
therapy in 50.9% of these patients. The most prevalent contraindication was time
delay in the prehospital phase in 38.2%, followed by advanced age in 34.5%.
Medical contraindications to thrombolytic treatment were found to be present in
only 10.9%. Extension of the prehospital time delay to 24 hours would have
increased the candidates for thrombolytic treatment to 39.3%, and raising the
upper age limit by 5 years would have increased them to 46.8%. CONCLUSIONS: Our
figures for a theoretically adequate thrombolysis rate contrast with many
previous studies and the clinical reality in different hospitals both in
Switzerland and around the world. In view of the importance and socioeconomic
consequences of thrombolytic treatment in myocardial infarction, studies focusing
on possible reasons for discrepancies between guidelines for thrombolytic therapy
and their implementation in hospital practice would appear to be a necessity in
providing measures to improve patient care in this clinical setting.
PMID- 9642754
TI - [National Research Program NFP 38: "Diseases of the nervous system"].
AB - The aim of Programme 38 of the Swiss National Research Foundation is to enhance
collaboration between basic science and clinical application, as related to
diseases of the nervous system, over a 5-year period. The 15 ongoing projects are
described. They are mainly concerned with mechanisms of pathogenesis and recovery
of function, and ways of modifying them therapeutically after traumatic lesions
or various diseases of the nervous system such as stroke, Parkinson's disease,
Alzheimer's dementia, depression, meningitis, HMSN etc.
PMID- 9642755
TI - [Acute abdomen in established multiple myeloma].
PMID- 9642756
TI - [Electroencephalography in the human].
PMID- 9642757
TI - [Prolonged video EEG monitoring in differential diagnosis of seizures and in
presurgical epilepsy diagnosis].
AB - Prolonged video-EEG-monitoring facilitates a correlation of clinical seizure
semiology and corresponding EEG changes. Indications for prolonged video-EEG
monitoring comprise differential diagnosis of epileptic and psychogenic seizures,
correct classification of epileptic syndromes and presurgical evaluation of
patients with medically refractory focal epilepsies. 6000 patients in Austria
would benefit from epilepsy surgery with an additional 150 bis 200 new patients
appearing each year. Presurgical evaluation consists of a non-invasive Phase I
and an invasive Phase II. During Phase I each patient is evaluated with a
prolonged video-EEG-monitoring with scalp-EEG, a MRI-scan, a SPECT- and/or PET
scan, a neuropsychological evaluation and a Wada-test. If the epileptogenic zone
cannot be localized adequately with these methods, invasive electrophysiological
techniques with intracranial (epidural peg-electrodes, foramen-ovale electrodes,
subdural strip or grid electrodes) or intracerebral electrodes (stereotaxically
implanted depth electrodes) have to be applied. Epilepsy surgery renders 70 to
80% of patients seizure free and thus can regarded an effective and safe
treatment option for patients with medically refractory focal epilepsies.
PMID- 9642758
TI - [Evoked potentials--indications and clinical value].
AB - This paper deals with studies of evoked potentials in diseases of the peripheral
and central nervous system. Indications and clinical value of visual evoked
potentials, brain stem auditory evoked potentials, somatosensory evoked
potentials and motor evoked potentials are evaluated for frequent neurological
diseases.
PMID- 9642759
TI - [Electrodiagnosis of focal neuropathies].
AB - Electrodiagnostic techniques used in an EMG-Laboratory and the diagnostic value
in focal mononeuropathies are presented. The electrodiagnostic techniques include
nerve conduction studies and needle electrode examination. Measurement of distal
latency, amplitude, conduction velocity and the finding of focal conduction block
may localize the focal character of the mononeuropathy. The needle electrode
examination gives further information about distribution, extent, activity, or
chronicity of the disease, especially in cases with axonal injuries. Some normal
electrodiagnostic patterns are presented, accompanied by some illustrative
pathological cases.
PMID- 9642760
TI - [Role of electrophysiology in diagnosis of polyneuropathies].
AB - Most for polyneuropathies present in a uniform, distally accentuated, rather
symmetrical pattern, although asymmetric or multifocal distributions occur. The
main feature of diagnosis is the history of development and the neurological
clinical examination. Neurophysiologic studies, mainly nerve conduction studies
(motor and sensory), reflex studies and electromyography are very accurate, but
unspecific tools in order to establish the diagnosis of polyneuropathies, define
special electrophysiologic features and can also reveal undetected (subclinical)
lesions. For clinical purposes most neuropathies can be divided according the
nerve conduction studies in axonal, demyelinating and mixed types. In recent
years additional electrophysiological features as conduction block have appeared
and are still under discussion. The etiology of polyneuropathy has to be
determined in each patient with scrutinity. Additionally to general diseases
(e.g. diabetes), common toxins (e.g. alcohol), concurrent medication (e.g. some
cytostatic drugs) also immunologic (e.g. vasculitis) and hereditary factors have
to be considered. A nerve biopsy is only indicated after a thorough consideration
of electrophysiology and ancilliary findings. This applies in particular to
hereditary neuropathies, where genetic testing has become a highly reliable test
replacing biopsy.
PMID- 9642762
TI - [Statistics--lying, but properly].
PMID- 9642761
TI - [Electromyography in myopathies].
AB - Despite increasing importance of molecular genetics, electromyography has
preserved its place as a valuable tool in the diagnostic procedure of myopathies.
Conventional electromyography allows the assessment of spontaneous activity,
motor unit action potentials and interference patterns. In myopathies,
fibrillations and positive sharp waves can be found in the majority of the cases.
Motor unit action potentials are of short duration, low amplitude and may show
increased polyphasia and number of satellite potentials. The interference pattern
may be of low amplitude and compact already at submaximal contraction. Compared
to conventional electromyography, automatic interference pattern analysis
provides quantitative results and has the higher sensitivity and specificity.
Normal conventional or automatic electromyography does not exclude a myopathy.
For diagnostic purposes, electromyography will be followed by muscle biopsy and
DNA analysis in most of the cases.
PMID- 9642763
TI - [Important results of about 45 years balneo-medical research in Bad Hall].
AB - It was tried to show the most essential results of a approximately 45 years'
research activity on the field of iodine balneology from the Paracelsus Institute
and--since 1993--from the Paracelsus-Gesellschaft Bad Hall. The papers were
concerned with: basical studies about the chemistry of the iodine waters,
generation of special analytic methods and techniques for iodine determinations
and for investigations of the iodine metabolism, generation of new therapeutical
iodine applications (for example: eye iontophoresis, electro-aerosol; preparation
of the iodine water for a mineral water indoor swimming-bath and for special
therapy solutions), investigation of the (favourable) iodine effects on the
cardiac and circulation system, on blood rheology, thyroid function, lipid
metabolism and on the antioxidant defence mechanisms (with special consequences
for arteriosclerosis, diabetes mellitus and cataract), also on visual function
and eye diseases (retina, color perception, contrast sensitiveness, cataract, dry
eye) and respiratory diseases. Comparative studies on patients and on
experimental animals as well as model experiments (e.g. on connective tissue: in
vitro studies; tissue cultures) have been used to objectify many empirically
observed cure effects. Possible side-effects of a cure with iodine brine (e.g.
iodism) were mentioned.
PMID- 9642764
TI - Validation of antibody-based recognition by piezoelectric transducers through
electroacoustic admittance analysis.
AB - The development of immunosensors based on piezoelectric transducers is widely
investigated due to their attractive potentialities. The quartz crystal
microbalance (QCM) may give a direct response signal which characterizes the
binding event between a sensitive layer, immobilized onto the surface transducer,
and the analysis to be detected. However, for small biomolecules, such as some
antigens, it is quite difficult to obtain an observable signal. This is mainly
due to the lack of sensitivity of the commonly used QCM (5 to 10 MHz quartz
crystal). Moreover, the mass estimated with the QCM response through the
Sauerbrey equation and the mass which can be measured thanks to other analytical
techniques, in our case an enzymatic assay, are different: the deposited mass is
generally overestimated by the QCM. To validate QCM mass measurements and,
therefore antigens recognition, the interactions of acoustic shear waves with a
biolayer were investigated during enzyme adsorption onto the microbalance gold
electrode or during the antibody/antigen binding. Electroacoustic admittance was
measured around the resonance frequency of a 27 MHz quartz resonator in parallel
with microbalance measurements. The parameters which characterize the quartz
microbalance equivalent circuit were compared with the classical microbalance
frequency. The mass overestimation, given by the microbalance, could be explained
either by modification of the rheological properties of the sensitive layers
and/or by an inadequacy of the assay performed.
PMID- 9642765
TI - Visual detection of protein adsorption onto electrochemically oxidized aluminum
surfaces.
AB - Adsorption of proteins onto electrochemically oxidized aluminum surfaces by a
simple visual observation was investigated. For this purpose, Ta and then A1 were
sputtered onto glass slides (Al/Ta/glass slides). Al/Ta/glass slides were
electrochemically oxidized in 0.4 M H3PO4 under the potentiostatic conditions.
After the application of aqueous solutions of bovine, rabbit or human
immunoglobulin onto the solid Al2O3 surfaces, a change in colour was monitored
visually. It was found that all investigated proteins could successfully be
adsorbed onto oxidized Al surfaces. This was manifested by a change in colour of
the surface from tan to a purple or blue, depending on the concentration of
proteins, coating time and degree of oxidation of the Al layer. Most importantly,
when an aqueous solution of human IgG was applied on an anti-human IgG coated
surface, a change in colour was also observed indicating that the adsorption
process did not denature the molecular recognition sites. This type of antibody
antigen reaction was confirmed on the example of anti-human prothrombin--human
prothrombin. It is believed that this technology may be useful in developing
immunosensors for a variety of applications.
PMID- 9642766
TI - Sensing biological effectors through the response of bridged nucleic acids and
polynucleotides fixed in liquid-crystalline dispersions.
AB - The formation of three-dimensional structures of double-stranded nucleic acid and
polynucleotide molecules, fixed in the structure of liquid-crystalline
dispersions and bridged by polymeric chelate complexes is described. The bridging
elements consist of alternating daunomycin molecules and copper ions. It is shown
that these bridges between nucleic acid molecules stabilize cholesteric
structures of the DNA liquid-crystalline dispersion. The formation of polymeric
chelate bridges is accompanied by a remarkable increase of the intense circular
dichroism (CD) band characteristic of the DNA-daunomycin cholesterics. These
bridges are destabilized by a number of biologically relevant compounds and
macromolecules, such as ascorbic acid, homocarnosine, bovine serum albumin and
lysozyme. The dramatic change in the optical activity of the liquid-crystalline
dispersions upon addition of these compounds makes them easily detectable. The
sensitivity of the method, in the range of analytic concentration 10(-4)-10(-8)
M, depends on the nature of the compound being tested. The response of bridged
DNA structures to biological effectors observed here foresees their further
development as biosensor devices for detecting the presence of biologically and
pharmacologically relevant compounds.
PMID- 9642767
TI - Genetic engineering of a single-chain antibody fragment for surface
immobilization in an optical biosensor.
AB - The development of a biosensor based on a genetically engineered biomolecule
offers many potential advantages to sensors that rely on natural proteins only.
Here we present how protein engineering techniques can be used to introduce a
functional unit for surface immobilization into a single-chain antibody fragment
(scFv). A peptide known to mimic the binding properties of biotin was fused to
the carboxyterminus of the phosphorylcholine-binding scFv fragment of IgA
McPC603. This fusion protein could be immobilized on a streptavidin monolayer.
The resulting scFv monolayer was capable of binding a fluorescently labeled
phosphorylcholine analog, as detected by total internal reflection fluorescence.
In contrast, an scFv monolayer formed by introducing biotin through chemical
modification was not capable of binding phosphorylcholine. These results
demonstrate the utility of site-specific, oriented attachment strategies in the
formation of protein monolayers in optical sensors, made possible by the use of
protein engineering techniques.
PMID- 9642768
TI - Analytical strategies for amperometric biosensors based on chemically modified
electrodes.
AB - Various strategies based on the use of chemically modified electrodes for the
development of amperometric biosensors are described. Particular emphasis is
placed on materials capable of catalyzing the oxidation of NADH and coupling
these with enzymatic activities for biosensor construction. In terms of
electrocatalysts, the discussion will centre on electrodeposited films of 3,4
dihydroxy benzaldehyde (3,4-DHB) and related analogs as well as on
electrodeposited films of transition metal complexes of 1,10-phenanthroline-5,6
dione (phen-dione). Electrodeposited films of these materials have been coupled
to the enzymatic activity of aldehyde dehydrogenase and alcohol dehydrogenase for
the development of biosensors for aldehydes and ethanol, respectively.
PMID- 9642769
TI - Simultaneous determination of maltose and glucose using a screen-printed
electrode system.
AB - A screen-printed sensor system consisting of a glucose oxidase (GOD) electrode
and an amyloglucosidase/glucose oxidase (A/G) electrode was constructed to
determine maltose and glucose simultaneously in a mixture. Sensor construction
was optimised so that it contained 20 units of GOD/40 units of amyloglucosidase
and 0.2 mM 1,1'-ferrocenedimethanol. These components were deposited onto a
screen-printed carbon electrode and an outer membrane was printed from 3.5%
hydroxyethyl cellulose (HEC) solution. The optimum pH was 4.8. The linear range
of the system was up to 40 mM glucose or 20 mmol/L maltose with coefficients of
variation (CVs) ranging from 3.5% to 5.29%. The results obtained by using the
enzyme electrode system agreed well with those obtained by the Fehling titration
method. When stored dry, especially at 4 degrees C, the enzyme electrodes showed
good stability over four months.
PMID- 9642770
TI - Surface modifications for the development of piezoimmunosensors.
AB - Four different techniques for the immobilisation of proteins onto the gold
electrode of a piezoelectric quartz crystal were investigated. The examined
techniques were adsorption, avidin-biotin binding and two different types of
covalent binding on self-assembled monolayers (SAM),
dithiobis(succinimidylpropionate) (DSP) and a dextran modified thiol monolayer.
The reaction of the immobilised proteins (bovine serum albumin (BSA) and anti
human IgG) with their specific antibodies, anti-BSA and hIgG (50 and 200
micrograms/ml) were studied using a quartz crystal microbalance and then
compared. Many cycles of measurements were performed on the same crystal
regenerating the gold surface with a solution of glycine.HCl, 100 mM, pH 2.1. The
interactions of the immobilised reagents with non-specific antibodies were also
studied. The adsorption protocol was the quickest, but did not allow regeneration
with glycine.HCl. Thiol-dextran coated surfaces did not show any detectable
response to non-specific reagents, but needed a very long and complicated
protocol. DSP and avidin-biotin coating procedures were easy and not too long.
They seemed to have the best characteristics of reproducibility among different
crystals and possibility of regeneration of the coated surface, but the
percentage of non-specific binding was high.
PMID- 9642771
TI - An approach to conductometric immunosensor based on phthalocyanine thin film.
AB - A new approach to conductometric biosensors utilizing iodine-sensitive
phthalocyanine thin films has been proposed. The excellent sensitivity of the
tetra-tert-butyl copper phthalocyanine (ttb-CuPc) to free iodine was used for the
first time to detect a peroxidase-initiated reaction in an aqueous medium. To
minimize the interfering effect of aqueous electrolytes on the impedance
responses of the ttb-CuPc film itself, Au/Cr interdigitated planar electrodes
bearing ttb-CuPc thin films were protected with hydrophobic gas-permeable
membranes, namely thermally evaporated calixarene or plasma polymerized
hexamethyldisiloxane films. Impedance spectroscopy data were analyzed in order to
define the optimal operating frequency. An enzyme sensor with peroxidase
immobilized in a cross-linked albumin matrix was tested. Its impedance responses
were studied under variation of the substrate concentration, pH, ionic strength
and buffer capacity. These results were used to define conditions for peroxidase
linked immunoassay in subsequent tests. With the developed sensor, concentrations
of IgG in 0.2-2 micrograms/ml range were measured in a competitive mode with
satisfactory accuracy. The detection of IgG in both test solutions and blood
serum samples has been demonstrated.
PMID- 9642772
TI - Electropolymerization of pyrrole and immobilization of glucose oxidase in a flow
system: influence of the operating conditions on analytical performance.
AB - The in situ potentiostatic electropolymerization of pyrrole (Py) on a Pt
electrode in a thin-layer amperometric cell and the entrapment of the enzyme
glucose oxidase (GOx) for the determination of glucose are reported. Polypyrrole
(PPy) is directly formed by continuous passage of a buffered solution of the
monomer (0.4 M) and enzyme (250 U mL-1) at pH 7 at a flow rate of 0.05-0.1 mL min
1 under a constant applied potential of +0.85 V vs Ag/AgCl decreases. The
electrosynthesis of PPy by injection of 500 microL of a Py + GOx solution in a
carrier electrolyte consisting of 0.05 M phosphate buffer and 0.1 M KCl at pH 7.0
was also assayed. The influence of the electropolymerization conditions on the
analytical response of the sensor to glucose was investigated. The analytical
performance of the PPy/GOx sensor was also studied in terms of durability and
storage life, as well as selectivity against electroactive species such as
ascorbic acid and uric acid as a function of the thickness of the polymer film
formed.
PMID- 9642773
TI - Covalent coupling of immunoglobulin G to a poly(vinyl)alcohol-poly(acrylic acid)
graft polymer as a method for fabricating the interfacial-recognition layer of a
surface plasmon resonance immunosensor.
AB - The synthesis of a terminally thiolated poly(vinyl)alcohol (PVA) grafted with
Poly (acrylic acid) (PAA) side chains is described. The PVA-PAA graft polymer
(PVAg) was end-tethered to silver surfaces via the terminal thiol functionality
and the resultant mobile, hydrophilic polymer matrix exploited for the covalent
immobilization of large quantities of polyclonal goat (anti-hIgG) antibody (IgG)
with low levels of non-specific adsorption. An SPR immunosensor, fabricated with
an IgG-PVA-silver interfacial layer proved capable of performing a sensitive
label-free assay of human IgG antigen (hIgG) with minimal non-specific binding
interference. A detection limit (DL) for hIgG from serum of 0.8 microgram/ml (5
nM) and an assay sensitivity of 0.66 ng hIgG/mm2/nM are reported.
PMID- 9642774
TI - Detection of multiple toxic agents using a planar array immunosensor.
AB - A planar array immunosensor, equipped with a charge-coupled device (CCD) as a
detector, was used to simultaneously detect 3 toxic analytes. Wells approximately
2 mm in diameter were formed on glass slides using a photoactivated optical
adhesive. Antibodies against staphylococcal enterotoxin B (SEB), ricin, and
Yersinia pestis were covalently attached to the bottoms of the circular wells to
form the sensing surface. Rectangular wells containing chicken immunoglobulin
were used as alignment markers and to generate control signals. After removing
the optical adhesive, the slides were mounted over a scientific grade CCD
operating at ambient temperature in inverted (multipin phasing) mode. A two
dimensional graded index of refraction lens array was used to focus the sensing
surface onto the CCD. Solutions of toxins were then placed on the slide. After
rinsing, Cy5-labeled antibodies were introduced. The identity and amount of toxin
bound at each location on the slide were determined by quantitative image
analysis. Concentrations as low as 25 ng/mL of ricin, 15 ng/mL of pestis F1
antigen, and 5 ng/mL of SEB could be routinely measured.
PMID- 9642775
TI - Monitoring specific interaction of low molecular weight biomolecules on oxidized
porous silicon using ellipsometry.
AB - Porous silicon dioxide surfaces have been used for monitoring the specific
affinity binding of low molecular weight molecules to streptavidin. Streptavidin
was immobilized to the porous silicon dioxide surface by spontaneous adsorption
at pH 7.4. Binding of biotin and an oligopeptide synthesized by means of
combinatorial chemistry were monitored with an in situ null ellipsometer.
Measurements were also done with hydroxy-azobenzene-2-carboxylic acid and DL-6-8
thioctic acid amide. The performance of porous silicon dioxide as a potential
surface in biosensor applications was compared with a planar silicon dioxide
surface. Porous silicon dioxide showed a 10-fold amplification of the response
compared to planar silicon dioxide. It was possible to monitor the binding of
biotin and the oligopeptide in the concentration range 2-40 microM. A response
time as low as 30 s was obtained for the oligopeptide at 40 microM.
PMID- 9642776
TI - DNA optical sensor: a rapid method for the detection of DNA hybridization.
AB - A DNA optical sensor system is proposed based on the combination of sandwich
solution hybridization, magnetic bead capture, flow injection and
chemiluminescence for rapid detection of DNA hybridization. Bacterial alkaline
phosphatase (phoA) gene and Hepatitis B virus (HBV) DNA were used as target DNA.
A biotinylated DNA probe was used to capture the target gene onto the
streptavidin-coated magnetic beads and a calf intestine alkaline phosphatase
(CAP)-labelled DNA probe was used for subsequent enzymatic chemiluminescence
detection. The detection cycle was less than 30 min, excluding the DNA
hybridization time, which was about 100 min. Both the phoA gene and HBV DNA could
be detected at picogramme or femtomole level. No response signal was obtained
when target DNA did not exist in the sample. Successive sample detection could be
made by removing the magnetic field and a washing step.
PMID- 9642777
TI - Functional characterization of a conducting polymer-based immunoassay system.
AB - Experiments have been performed to characterize the electrical properties and
functionality of a poly(3-hexylthiophene)-coated platinum electrode developed as
a sensor for immunoassay read-out. Admittance measurements were performed on the
coated electrodes as a function of frequency. The admittance spectra obtained
show that the sensor is capacitive in nature. A circuit model is presented for
comparison to other conducting polymer systems. Dynamic sensor response is
characterized by oxidizing the polymer via a hydrogen peroxide-iodide pathway.
Hydrogen peroxide is introduced either by direct injection or through a glucose
glucose oxidase reaction to determine electrode functionality and sensitivity.
Sensor response to chemical oxidation is measured as a function of frequency and
applied signal amplitude. System response is linear in frequency from 1 Hz to 70
Hz and in excitation amplitude up to approximately 600 mV. System sensitivity is
analyzed based on oxidant generation from the enzyme-initiated pathway, sensor
baseline drift, and the noise band on the quiescent sensor current.
PMID- 9642778
TI - Influence of anions on glucose electrode response: application to extending
concentration range.
AB - Nitrate anions are shown to be very effective inhibitors of glucose oxidase at
acidic pH, much more so than halide anions. The inhibition is fully reversible.
This effect could be used to extend the concentration range of glucose electrodes
up to 0.556 M (100 g/l) at pH 4 in 0.5 M KNO3 and glucose could be assayed in
undiluted fruit juices. The disadvantages of this method are: prolonged time of
one measurement; and the loss of accuracy owing to very low response of the
electrode.
PMID- 9642780
TI - Current awareness in biosensors & bioelectronics.
PMID- 9642779
TI - Bioelectronic noses: a status report. Part I.
AB - The present state of the art to record or mimic electronically the human senses
of olfaction and taste is characterized. In this part I, an introduction to our
present understanding in the development of electronic and bioelectronic noses is
given. Finally the natural olfactory system is described in detail.
PMID- 9642781
TI - Personality dimensions in spotted hyenas (Crocuta crocuta).
AB - Personality ratings of 34 spotted hyenas (Crocuta crocuta) were made by 4
observers who knew the animals well. Analyses suggest that (a) hyena personality
traits were rated with generally high reliability; (b) 5 broad dimensions
(Assertiveness, Excitability, Human-Directed Agreeableness, Sociability, and
Curiosity) captured about 75% of the total variance; (c) this dimensional
structure could not be explained in terms of dominance status, sex, age, or
appearance; and (d) as expected, female hyenas were more assertive than male
hyenas. Comparisons with previous research provide evidence for the cross-species
generality of Excitability, Sociability, and especially Assertiveness. Discussion
focuses on methodological issues in research on animal personality and on the
potential contributions this research can make for understanding the biological
and environmental bases of personality.
PMID- 9642782
TI - Use of experimenter-given cues during object-choice tasks by chimpanzees (Pan
troglodytes), an orangutan (Pongo pygmaeus), and human infants (Homo sapiens).
AB - In a series of experiments, chimpanzees (Pan troglodytes), an orangutan (Pongo
pygmaeus), and human infants (Homo sapiens) were investigated as to whether they
used experimenter-given cues when responding to object-choice tasks. Five
conditions were used in different phases: the experimenter tapping on the correct
object, gazing plus pointing, gazing closely, gazing alone, and glancing without
head orientation. The 3 subject species were able to use all of the experimenter
given cues, in contrast to previous reports of limited use of such cues by
monkeys.
PMID- 9642783
TI - Object permanence in orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri
sciureus).
AB - The authors tested orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri
sciureus) on object permanence tasks. In Experiment 1, orangutans solved all
visible displacements and most invisible displacements except those involving
movements into 2 boxes successively. In Experiment 2, performance of orangutans
on double invisible displacements and control displacements (assessing simple
strategies) was compared. Orangutans did not use the simple strategy of selecting
the box visited last by the experimenter. Instead, poorer performance on double
invisible displacements may have been related to increased memory requirements.
In Experiment 3, squirrel monkeys were tested using the procedure of Experiment
1. Squirrel monkeys solved visible but did not comprehend invisible
displacements. Results suggest that orangutans but not squirrel monkeys possess
Stage 6 object permanence capabilities.
PMID- 9642784
TI - Timing of presentation of prenatal auditory stimulation alters auditory and
visual responsiveness in bobwhite quail chicks (Colinus virginianus).
AB - One group of bobwhite quail embryos (Colinus virginianus) was exposed to 10
min/hr of bobwhite chick contentment calls immediately followed by 10 min/hr of
bobwhite chick distress calls. A 2nd group of embryos was exposed to the same
auditory stimulation but in the opposite order of presentation. Postnatal testing
revealed that chicks exposed prenatally to the bobwhite chick contentment call
and distress call (in either order of presentation) continued to respond to
maternal auditory cues into later stages of postnatal development compared with
unmanipulated chicks. Chicks exposed prenatally to the contentment call followed
by the distress call showed an accelerated pattern of visual responsiveness to
maternal cues, whereas chicks exposed prenatally to the distress call followed by
the contentment call showed deficits in the normal pattern of perceptual visual
responsiveness, suggesting that the auditory stimulation precocial avian embryos
encounter 1st is influential in directing early intersensory development.
PMID- 9642785
TI - Modified sensory features of social stimulation alter the perceptual
responsiveness of bobwhite quail chicks (Colinus virginianus).
AB - This study examined the sensory features of postnatal social experience that
bobwhite quail chicks (Colinus virginianus) require to maintain species-typical
responding to maternal auditory-visual cues. Chicks were reared in 1 of 3
conditions after hatching: altered tactile, auditory, or visual experience with
siblings. Findings revealed that altered tactile, auditory, or visual experience
during the first 36 or the first 72 hr following hatching modified chicks'
preferential responding to species-specific maternal cues. During the second 36
hr, altered tactile or auditory experience disrupted chicks' perceptual
development, whereas altered visual experience did not affect species-typical
responsiveness. Results indicate that (a) timing of early postnatal visual
experience can affect early filial responsiveness to maternal cues and (b) normal
sensory experience derived from early social interaction affects species-typical
perceptual development.
PMID- 9642786
TI - Status, age, and sex effects on performance of discrimination tasks in group
tested rhesus monkeys (Macaca mulatta).
AB - To assess the relation between performance and social or demographic variables,
this study group tested a captive monkey colony on visual and manual
discrimination problems. Animals could choose between differently colored, sand
filled boxes, where hue signaled the initial probability of finding buried food
items. Dominant animals and subadults were most successful in locating and
retrieving incentives, but sex did not affect performance. Rank effects occurred
without overt aggression, suggesting deference by subordinates as a mediating
mechanism. Age effects may reflect changing attention patterns only evident in
complex arenas where cue salience becomes diluted. Because these findings differ
from studies of singly tested animals, they show that, in a social context, an
individual's rank and age may define opportunities to gain or efficiently use
information.
PMID- 9642787
TI - Distinguishing intentional from accidental actions in orangutans (Pongo
pygmaeus), chimpanzees (Pan troglodytes), and human children (Homo sapiens).
AB - This study investigates the understanding of others' intentions in 2- and 3-year
old children, chimpanzees (Pan troglodytes), and orangutans (Pongo pygmaeus).
During training, subjects learned to use a discriminative cue to select a baited
box. During testing, the experimenter placed a marker on top of the baited box to
inform the subject of the reward's location. However, the experimenter also
accidentally dropped the marker on top of an unbaited box, so that during any
given trial the experimenter marked 2 boxes, 1 intentionally and 1 accidentally.
All 3 species preferentially selected the box the experimenter had marked
intentionally (especially during the initial trials), with 3-year-old children
presenting the most robust results. These findings suggest that subjects
understood something about the experimenter's intentions. The authors speculate
that understanding of others' intentions may precede the understanding of others'
beliefs both at the ontogenetic and phylogenetic levels.
PMID- 9642788
TI - Why some capuchin monkeys (Cebus apella) use probing tools (and others do not).
AB - Tufted capuchins (Cebus apella) were provided with a task that facilitated the
use and modification of sticks as probing tools. It was found that subjects aged
10 years or older at initial task exposure were less likely to use tools than
were younger subjects. Furthermore, juveniles whose mothers died before the
subjects were aged 3 years were less likely to use tools than were juveniles
whose mothers survived through this period. The ability to use tools was not
related to subject sex or to access to the tool site or raw tool materials.
Subjects modified tools both before and during their use, and the relative
percentage of tools modified increased with subject age. Thus, it appears that
capuchins most readily acquire tool use before the age of 10 years and that early
disruption of the mother-infant relationship has deleterious effects on the
emergence of instrumental behavior.
PMID- 9642789
TI - Serous gland dimorphism in the skin of Melanophryniscus stelzneri (Anura:
Bufonidae).
AB - Two serous gland types (I and II) in the skin of the Argentine toad
Melanophryniscus stelzneri were discovered using light and electron microscopy.
Glands of the two types differ in several traits: features of the products (both
mature and immature), organelles involved in biosynthesis, and paths of serous
maturation. No consistent differences, however, were detected between the
myoepithelial sheaths encircling the secretory units. Type I glands manufacture
vesicles containing a single dense body with a repeating substructure and conform
to the fundamental secretory line of bufonid skin, a secretory line involved in
biosynthesis of steroids. Type II glands synthesize granules of varying densities
and seem to belong to a line of glands that secrete proteinaceous products. The
occurrence of the two serous gland types in Melanophryniscus stelzneri is
discussed in a comparison with current literature on the morphofunctional
characteristics of anuran poison glands, which perform both regulative and
defensive roles. It is suggested that di- or polymorphism in serous glands is an
adaptive trait that allows differential release of active molecules on the body
surface.
PMID- 9642790
TI - Ovarian growth and folliculogenesis in breeding and nonbreeding females of a
social rodent, the Zambian common mole-rat, Cryptomys sp.
AB - Zambian common mole-rats are subterranean rodents that live in families with only
one female breeding. Her offspring remain in the parental nest and do not
reproduce. Behavioral experiments (Burda, '95) demonstrated that their apparent
"sterility" is based on incest avoidance and individual recognition of family
members. To elucidate whether some kind of morphologically apparent ovarian
suppression still takes place in daughters, ovaries of females of known age,
weight, and reproductive histories were examined histologically and
morphometrically. The body mass of old females (more than 3 years of age) begins
to decrease, and the ovaries seem to begin to atrophy at the age of about 3-6
years. Ovaries in neonates exhibited primordial and primary follicles, sometimes
clustered in nests. Ovaries of adult nonbreeding females expressed all stages of
the follicular development up to tertiary follicles. Many unruptured luteinized
follicles were present, but true corpora lutea as a morphological sign of
ovulation were missing. Unruptured luteinized follicles also could be found
(additionally to true corpora lutea) in ovaries of breeding females. The number
of primordial follicles dropped rapidly during the first 2 years of age; the
number of primary, secondary, and tertiary follicles was subject to individual
variation; and there was no clear correlation with age or reproductive status.
While a tendency to form accessory unruptured luteinized follicles may just
reflect taxonomic affinities of bathyergids to hystricomorphs, the otherwise
complete folliculogenesis in "sterile" daughters and the presence of unruptured
luteinized follicles even in breeding females are further evidence that there is
no hormonal suppression of the ovarial cycle. We suggest that ovulation in
nonbreeding females is not actively suppressed by the breeding female, but
instead that it is not released because the triggering mechanisms, most probably
repeated copulation, are missing.
PMID- 9642791
TI - Ultrastructure of the foregut and associated glands in the lung fluke,
Paragonimus miyazakii (Digenea: Troglotrematidae), with particular reference to
their functional roles.
AB - The foregut and associated glands of a digenetic trematode, Paragonimus
miyazakii, were examined in the forebody by transmission and scanning electron
microscopy as well as by light microscopy, and their functional roles were
discussed. The foregut is lined with a general tegument without spines and
sensory receptors throughout its length, although it consists of the mouth,
pharynx, and esophagus. This foregut tegument is regionally and intraregionally
modified in appearance, suggesting the performance of auxiliary functions in
digestion. This appearance is characterized by long, frequent cytoplasmic
extensions of the apical tegument around the middle portion of the mouth and the
anterior esophagus. Electron-dense granules and multimembranous and multilamellar
bodies are developed in the tegument to various degrees, and elaborately in the
apical layer of the prepharynx. A single type of unicellular gland is embedded in
the antero-middle part of the worm in small groups. The gland cells synthesize
clear secretory granules as a chief product, each granule with a pleomorphic,
dense, core-like inclusion. Mature granules are elliptical in shape,
approximately 500 nm in diameter, and are subsequently discharged into the
prepharyngeal foregut lumen after passing through the elongated cytoplasm of the
gland cell. In the prepharynx and pharynx, host blood cells are apparently
processed for digestion. In the wide lumen of the esophagus, foodstuff could
undergo sufficient digestion prior to absorption by the cecal epithelium.
PMID- 9642792
TI - Experimental analysis of character coupling across a complex life cycle: pigment
pattern metamorphosis in the tiger salamander, Ambystoma tigrinum tigrinum.
AB - Developmental relationships among characters are expected to bias patterns of
morphological variation at the population level. Studies of character development
thus can provide insights into processes of adaptation and the evolutionary
diversification of morphologies. Here I use experimental manipulations to test
whether larval and adult pigment patterns are coupled across metamorphosis in the
tiger salamander, Ambystoma tigrinum tigrinum (Ambystomatidae). Previous
investigations showed that the early larval pigment pattern depends on
interactions between pigment cells and the lateral line sensory system. In
contrast, the results of this study demonstrate that the major features of the
adult pigment pattern develop largely independently of both the early larval
pattern and the lateral lines. These results suggest that ontogenetic changes
that occur across metamorphosis decouple larval and adult pigment patterns and
could thereby facilitate independent evolutionary modifications to the patterns
during different stages of the life cycle.
PMID- 9642794
TI - [Progress in the development of safer surgical procedures on the trachea and
bronchi].
PMID- 9642793
TI - Ontogeny of postcanine tooth form in the ferret, Mustela putorius (Carnivora:
Mammalia), and the evolution of dental diversity within the Mustelidae.
AB - This study describes dental development within the ferret, Mustela putorius,
through study of the form of the carnassial teeth and the upper first molar at
progressive growth stages. Primordial teeth were serially sectioned in sagittal
and transverse planes and three-dimensional reconstructions of tooth primordia
were generated using MacReco software. Regional growth of the crown and
asynchronous maturation of the dental tissues were observed in each tooth. The
upper carnassial blade develops early and the tooth increases in length rapidly.
Lingual growth of the upper carnassial is less pronounced and the protocone and
its surrounding region mature late. The lower carnassial blade develops early and
the talonid is late to mature. Development of the upper first molar differs from
carnassial development in the early emphasis upon transverse growth and reduced
lengthwise expansion. The early development of the carnassial blades in the
ferret is shared with other carnivores, and may reflect the functional
significance of this feature. Later stages of tooth ontogeny differ among
carnivoran taxa and the specialized morphology of ferret teeth results from an
apparently truncated period of late tooth ontogeny. This suggests that carnivoran
species may share a common path of early development that specifies the ontogeny
of homologous tooth features and that in later stages developmental differences
result in species-specific tooth forms.
PMID- 9642795
TI - [Bronchoplasty for the complete cure and preservation of pulmonary function].
PMID- 9642796
TI - [Tracheo-bronchoplasty--with special reference to the treatment outcome and
postoperative complications at anastomosis sites].
PMID- 9642797
TI - [Clinical significance of tracheo-bronchoplasty for patients with lung neoplasm-
distance from the edge of the tumor to the resection line].
PMID- 9642798
TI - [Progress on tracheo-bronchoplasty--study on minimal bronchoplasty and prevention
of surgical wound dehiscence].
PMID- 9642799
TI - [Progress on bronchoplasty--prognostic significance of bronchial artery
preservation].
PMID- 9642800
TI - [Laparoscopic surgery and treatment outcome in esophageal achalasia].
PMID- 9642801
TI - [Laparoscopic surgical procedure using the Jekler and Lhotka method in esophageal
achalasia].
PMID- 9642802
TI - [Changes in surgical procedures for patients with reflux esophagitis due to
recent introduction of laparoscopic surgery and proton pump inhibitors].
PMID- 9642803
TI - [New laparoscopic surgical procedure using surgical mesh for patients with
esophageal hernia].
PMID- 9642804
TI - [Different therapeutic approaches for patients with bronchogenic cysts within the
esophageal wall].
PMID- 9642805
TI - [Evaluation of new therapeutic procedures in benign esophageal diseases].
PMID- 9642806
TI - [Surgical therapy and follow-up on Stanford-A type dissecting aortic aneurysm].
PMID- 9642807
TI - [Operative outcome on Debakey-I type aortic dissection].
PMID- 9642808
TI - [Applicability of complete replacement of aorta viewed from early and remote
operative results].
PMID- 9642809
TI - [Strategy for improvement of operative results of broad aortic replacement for
DeBakey-I type aortic dissection].
PMID- 9642810
TI - [Surgical treatment of DeBakey-I type aortic dissection--with special reference
to patients receiving complete aortic replacement].
PMID- 9642811
TI - [Suitability of limited resection in lung cancer].
PMID- 9642812
TI - Intentional limited resection for primary lung cancer.
PMID- 9642813
TI - [Limited resection in primary lung cancer of peripheral origin].
PMID- 9642814
TI - [Combination of broad segmentectomy and lymph node excision for early stage lung
cancer as a standard operative method].
PMID- 9642815
TI - [Recurrence of lung cancer in the residual lobe following anatomic
segmentectomy].
PMID- 9642816
TI - [Thoracoscopic limited resection for lung cancer].
PMID- 9642817
TI - [Strategy for univentricular repair for complication of atrioventricular valve
regurgitation, total anomalous pulmonary venous connection, and ventricular
outflow obstruction].
PMID- 9642818
TI - [Therapeutic strategy in Fontan procedure].
PMID- 9642819
TI - [Surgical repair for single ventricle complicated with anomalous pulmonary venous
drainage or atrioventricular valve insufficiency].
PMID- 9642820
TI - [Strategy for univentricular repair for complication of atrioventricular
insufficiency or pulmonary venous obstruction].
PMID- 9642821
TI - [Strategy for Fontan procedure in asplenia syndrome associated with total
anomalous pulmonary venous connection].
PMID- 9642822
TI - [Surgical strategy for aortic valve stenosis associated with single ventricle who
will be objects of Fontan procedure].
PMID- 9642823
TI - [Strategy in annuloplasty for a juvenile patient with asymptomatic mitral valve
prolapse].
PMID- 9642824
TI - [Surgical treatment of mitral valve prolapse using the mitral apparatus to adjust
proper length of artificial chordae].
PMID- 9642825
TI - [Minimally invasive mitral valve plasty operations].
PMID- 9642826
TI - [Aortic valve-sparing operation--determination of proper graft size and
prevention of regurgitation ].
PMID- 9642827
TI - [Aortic valve-sparing operation and selection of operative technique].
PMID- 9642828
TI - [Annuloaortic repair for aortic regurgitation].
PMID- 9642829
TI - [Thoracoscopic excision of right upper mediastinal lymph node for bulky N3 left
lobe lung cancer].
PMID- 9642830
TI - [Endoscopic mediastinal lymph node excision for bulky N2 lung cancer].
PMID- 9642831
TI - [Combination of mediastinal lymph node excision and thoracoscopic pneumonectomy
for a case of N2 lung cancer confirmed by mediastinoscopy].
PMID- 9642832
TI - [Mediastinal and cervical lymph node excision for a case of stage-IV esophageal
cancer].
PMID- 9642833
TI - [Upper mediastinal lymph node excision for a case of stage-IV esophageal cancer].
PMID- 9642834
TI - [Lymph node excision for a case of stage-IV esophageal cancer].
PMID- 9642835
TI - [The Annals, which way does it go: the last two years (1996-1997)].
PMID- 9642836
TI - [AIDS-related cryptococcosis: diagnostic aspects, prognostic and therapeutic
implications].
AB - Diagnostic techniques of AIDS-related cryptococcosis were assessed in a series of
43 HIV-infected patients, and microbiological features were correlated to the
clinical course and outcome of disease. Polysaccharide antigen detection was the
most sensitive method for central nervous system infection, followed by direct
microscopy and culture: in 4 patients this visceral mycosis was initially
diagnosed by the detection of isolated cerebrospinal fluid antigen. Thirty-one
patients out of 43 suffered from disseminated infection (with positive blood
cultures and/or antigenemia). The occurrence of clinical relapses, a lethal
outcome, and time to relapses or to death, did not differ significantly between
patients with isolated central nervous system and those with disseminated
cryptococcosis.
PMID- 9642837
TI - [Modifications in diagnosis and therapy of osteoporosis after bone densitometry].
AB - The cost-benefit ratio of diagnostic procedures has become a major problem: in
particular, the expense of computerized bone mineral densitometry for
osteoporosis diagnosis has brought this issue to public attention. To avoid a
procedure considered costly, non-specialists often rely on standard radiography
alone for diagnosis. In this study, we evaluated the percent of cases in which
densitometry modified diagnosis and therapy based solely on radiographic
findings. Over a 10-month period, we recruited 133 consecutive post-menopausal
patients (average age 58.3 years, average time since menopause 12 years) who had
never undergone densitometry. Bone density at the lumbar (L1-L4) or femoral (non
dominant) level was measured with dual energy X-ray absorptiometry. The average
time between densitometry and the last radiographic examination was 13.6 months.
Ninety-one patients (68.4%) had a change in diagnosis following densitometry. In
42 cases (31.6%), the previous diagnosis remained unchanged (prevalence ratio
2.2; 95% confidence interval 1.6 to 2.7). Therapy was changed in 75.2% of the
cases (100 patients) and remained the same in 24.8% (33 patients; prevalence
ratio 3.0; 95% confidence interval 2.3 to 3.7). Our data underscore the
importance of densitometry in yielding quantitative data that are utilizable
during follow-up and able to support osteoporosis diagnosis and therapy.
PMID- 9642838
TI - [Effectiveness of long-term ACE-inhibition on pulmonary diffusion and ventilation
perfusion ratio in chronic heart failure: correlation with physical performance].
AB - Pulmonary dysfunction contributes to exercise intolerance in patients with
chronic heart failure, and ACE-inhibition improves the functional capacity of
these subjects. In this study, we investigated whether and how ACE-inhibitors
affect pulmonary function and ventilatory response during exercise in chronic
heart failure. Twenty patients with idiopathic dilated cardiomyopathy and left
ventricular ejection fraction < 35% underwent pulmonary function tests and
exercise evaluation with analysis of expired gases before and after 1 year of
treatment with enalapril (10 mg bid). To explore whether or not the respiratory
influence of ACE-inhibitors is peculiar to the syndrome of cardiac failure, we
also studied 19 subjects with mild, untreated primary hypertension who followed
the same protocol. In this group, enalapril exerted a neutral effect on pulmonary
function. In chronic heart failure patients, lung volumes were abnormal and did
not improve after enalapril treatment; on the contrary, alveolar diffusing
capacity for carbon monoxide increased towards normal values. Exercise tolerance
time, peak exercise oxygen consumption, ventilation, and tidal volume also
improved and the dead space to tidal volume ratio was reduced at the peak
exercise and intermediate exercise phases (20, 60 W). Changes in carbon monoxide
diffusion were positively correlated to those occurring during peak exercise
oxygen consumption. A negative correlation was found between the variations in
oxygen consumption and those in dead space to tidal volume ratio at peak
exercise. We conclude that in patients with chronic heart failure, ACE-inhibition
restores diffusing lung properties and improves ventilation-perfusion matching
during exercise. In this syndrome, sustained reduction in gas exchange resistance
is a fundamental therapeutic property of this class of drugs.
PMID- 9642839
TI - [Leukotriene antagonists in the treatment of asthma].
AB - Bronchial asthma is a chronic inflammatory disease of the airways. Several
mediators are involved in the inflammatory process, including leukotrienes B4,
C4, D4 and E4. These compounds promote bronchoconstriction, mucus hypersecretion,
eosinophil infiltration, monocyte/macrophage activation, and smooth muscle
proliferation. Two different approaches have been taken to interfere with
activity: 1) blocking of the specific cysteinyl leukotriene receptor, and 2)
inhibition of leukotriene biosynthesis (either by inhibition of the primary
enzyme, 5-lipoxygenase, or its required cofactor 5-lipoxygenase-activating
protein). Available data suggest that leukotriene modifier therapy is effective
in several experimental models of bronchial asthma. These agents also have
demonstrable efficacy in aspirin-induced asthma and against exercise and cold-air
induced bronchoconstriction. The recent 1997 NHLBI Expert Panel Report II
Guidelines suggest that leukotriene modifiers may be used as an alternative to
low dose inhaled corticosteroids in mild persistent asthma. They may also be
useful in more severe asthma, as supplements to inhaled corticosteroids and long
acting bronchodilators. The clinical benefit of leukotriene modifier therapy
occurs early in treatment. However, the response rate for leukotriene modifiers
approximates 70 to 80% suggesting that there are "responders" as well as "non
responders" for whom leukotrienes, as inflammatory mediators, may be less
important. A 2 to 4-week therapeutic trial, with objective monitoring of
response, may be a reasonable approach to initiating leukotriene modifier
therapy. Additional controlled trials will be required to define more fully the
role of these new drugs for long-term control and treatment of asthma.
PMID- 9642840
TI - [Clinical approach to the hypertensive patient. New guidelines].
AB - Prospective observational studies clearly show that the risks of stroke, coronary
artery disease, and premature death are directly related to blood pressure
levels. Yet as the results of prospective randomized intervention studies have
indicated, these risks are reduced by effective blood pressure control. Over a 5
year period, an average reduction of 5-6 mmHg in diastolic blood pressure and of
10-12 mmHg in systolic blood pressure is associated with a 38% decrease in risk
of stroke and a 16% decrease in risk of coronary heart disease. Although
awareness of hypertension has increased markedly, and the number of patients
treated for this condition has approximately doubled over the last 20 years,
premature morbidity and mortality remain higher than in the normotensive
population. This situation may arise from the inadequate level of blood pressure
control achieved in many patients. Thus, although delineating theoretical rules
to treat hypertension seems relatively easy, in real life it is not always
possible to adhere to them. This difficulty highlights the need for appropriate
guidelines in clinical practice. A number of national groups as well as the World
Health Organization and the International Society of Hypertension have recently
published recommendations for the diagnosis and treatment of hypertension.
Physicians must strive to improve the management of hypertension and remember
that a thorough clinical evaluation, treatment of associated cardiovascular risk
factors, prevention of target organ damage, and good patient compliance are key
elements affecting the success of therapy.
PMID- 9642841
TI - [Hormone replacement therapy and cardiovascular pathology in menopause].
AB - Although the incidence of vascular disease increases progressively with age, the
increment observed in women between 50 and 60 years old does not seem to be
directly correlated to the menopause. On the other hand, significant
modifications of some risk factors, particularly those related to lipid
metabolism and the hemostatic system have been observed in postmenopausal women.
It should be stressed that the results of these studies, although generally
concordant, cannot be applied directly to the entire population: the majority of
women studied were well-educated and from the upper-middle social and economic
classes and thus more prone to comply with behavioral and therapeutic precepts.
Moreover, non-white women were excluded from these studies. At present, numerous
data attest to the beneficial effect of hormone replacement therapy on
cardiovascular disease in postmenopausal women. The presently running National
Institutes of Health 9-year randomized primary prevention study (Women's Health
Initiative) and the secondary prevention "Heart Estrogen/Progestin Replacement
Study" should, within a few years, provide further and, it is hoped, definitive
information concerning the utility of hormone replacement therapy for the primary
and secondary prevention of cardiovascular disease.
PMID- 9642842
TI - Anaphylactic reaction to oral prednisone: a case report and review of the
literature.
AB - Reports of corticosteroid anaphylactic reactions are rare in the medical
literature. We describe the case of a nonatopic 17-year-old girl with bronchial
asthma and aspirin intolerance who developed a dramatic anaphylactic reaction to
oral prednisone. She recovered with shock therapy and intravenous administration
of diphenhydramine and hydrocortisone. Intradermal testing with a wide range of
steroid preparations gave positive results to prednisone. No reactions occurred
to methylprednisolone and hydrocortisone. This case and the brief review of the
literature which follows emphasize the danger of prednisone administration in
patients who have asthma and a history of drug intolerance.
PMID- 9642844
TI - [Patient-centered medicine].
AB - The dominant model in medical practice today has been defined as the "disease
centered" model. In the past few years, it has been attacked for oversimplifying
the problems of illness because it assumes disease to be fully accounted for by
deviations from the norm of measurable biological variables. This article
describes a patient-centered model that integrates the traditional understanding
of disease with each patient's experience of illness. The transformed clinical
method involves three major changes: 1) new tasks for the consultation: the
patient-centered method focuses on disease and on four principal dimensions of
the patients, i.e., their ideas about the illness, their feelings and fears, the
impact of their problems on their lives, their expectations about what should be
done; 2) new strategies to obtain these objectives: new interviewing skills and
communication techniques, e.g., attentive listening; open questions; 3) new modes
of teaching and learning, e.g., the use of role-playing and videotaping. Research
has shown that patient-centered medicine enables better clinical results to be
obtained and is associated with increased patient and physician satisfaction.
PMID- 9642843
TI - Venous thromboembolism after laparoscopic surgery: two case reports and review of
the literature.
AB - Two cases of deep vein thrombosis and pulmonary embolism in patients who had
undergone laparoscopic surgery (cholecystectomy and inguinal hernioplasty in the
first and crural hernioplasty in the second) are described. These cases suggest
that prophylaxis for venous thromboembolism should also be given to patients who
undergo relatively noninvasive surgery such as laparoscopic intervention. The
presentation concludes with a review of the last 7 years' literature on this
topic.
PMID- 9642845
TI - HIV infection of CD8 lymphocytes: a critical step for the disease?
PMID- 9642846
TI - A learning model of binge eating: cue reactivity and cue exposure.
AB - In the present article, a learning model of binge eating is presented. It has
been hypothesized that, parallel to drug intake, the craving and excessive food
intake of binge eaters is cue controlled. Research in support of the model is
reviewed and a series of predictions about clinical and non-clinical issues is
derived from the model. Amongst other things, the model predicts that binge
eating might be successfully treated with cue exposure and response prevention.
Practical issues are discussed and preliminary pilot studies on cue exposure for
bingers are reviewed.
PMID- 9642847
TI - The relevance of associative learning pathways in the development of obsessive
compulsive washing.
AB - The relevance of associative learning in the development of Obsessive-Compulsive
Disorder (OCD) was investigated in a group of 23 OCD patients whose main concern
was washing and 23 age and sex matched control subjects who did not have OCD. OC
washers completed an origins instrument based on Menzies and Clarke's (1993,
Behaviour Research and Therapy, 31, 355-365) Origins Questionnaire (OQ) for the
phobic disorders. Control subjects completed a modified version of this measure
designed to give a comprehensive picture of their experiences with relevant
contamination-related stimuli. In general, the results question the relevance of
associative-learning per se in the development of OC washing. Direct and indirect
conditioning events were very rare in the OCD group, accounting for less than 13%
of cases. No significant differences between groups were found in the proportion
of subjects who knew other OC washers, or had experienced direct associative
learning events prior to onset. Contrary to expectation, significantly more non
OCD subjects had experienced vicarious learning events related to dirt and
washing than OCD subjects. However, of note, associative-learning events that
took place during episodes of depression were significantly more frequently
reported in the OCD group than in the control group. Depression appeared to play
a facilitating role in the associative-learning of OC washing. The implications
of these findings for theoretical accounts of OCD are discussed.
PMID- 9642848
TI - No superior perception of hyperventilatory sensations in panic disorder.
AB - It has been argued that panic disorder patients may be more skilled at detecting
changes in actual physiology than others. The present study investigated if panic
patients are better than controls in perceiving sensations produced by light
hyperventilation. Twelve panic patients and 28 control subjects underwent a
procedure in which they were exposed 12 times to 1 min of light hyperventilation
or 1 min of 'placebo' hyperventilation (isocapnia). Differences in sensations
reported during real hyperventilation were compared to sensations reported during
'placebo' hyperventilation. Results demonstrated an absence of superior
perception of hyperventilatory sensations in panic patients.
PMID- 9642849
TI - Etiology of childhood phobias: current status of Rachman's three pathways theory.
AB - Despite advances in the assessment and treatment of childhood phobias, little is
known about their etiology. Rachman has proposed that phobias are acquired
through three different pathways: direct conditioning, modeling or
instructions/information. We evaluate the empirical support for Rachman's theory
in relation to the origins of childhood phobias. Although we find support for
Rachman's theory, a number of methodological and theoretical issues are
emphasized. For example, insufficient attention has been given to the reliability
and validity of retrospective subject reports on the acquisition of childhood
phobias. Also some findings on the origins of childhood fears and phobias are
more consistent with a nonassociative account of phobia onset, thus providing an
interesting challenge to Rachman's theory.
PMID- 9642850
TI - Detection of negative and positive audience behaviours by socially anxious
subjects.
AB - Nineteen subjects high in social anxiety and 20 subjects low in social anxiety
were asked to give a 5-min speech in front of three audience members. Audience
members were trained to provide indicators of positive evaluation (e.g., smiles)
and negative evaluation (e.g. frowns) at irregular intervals during the speech.
Subjects were instructed to indicate, by depressing one of two buttons, when they
detected either positive or negative behaviours. Results indicated that subjects
high in social anxiety were both more accurate at, and had a more liberal
criterion for, detecting negative audience behaviours while subjects low in
social anxiety were more accurate at detecting positive audience behaviours.
PMID- 9642851
TI - Recognition bias for safe faces in panic disorder with agoraphobia.
AB - Panic patients with agoraphobia were compared with normal controls on tasks of
face recognition. The subjects were presented with 20 photos, and were required
to make a judgement of the persons on the photos; shortly afterwards they were
unexpectedly presented with a recognition task. In the first study, one task was
to judge whether the persons on the photos were critical or accepting: unlike
social phobics (Lundh and Ost, 1996b, Behaviour Research and Therapy, 34, 787
794), panic patients showed no bias for critical vs accepting faces on the
recognition task. In a secondary study, the task was to judge whether the persons
on the photos were 'safe' or 'unsafe', i.e. whether they could be relied on if
the subject would need help in some situation. The results showed a recognition
bias for safe vs neutral faces in panic patients. The index of recognition bias
for safe faces correlated with avoidance of feared situations when accompanied by
others, as measured by the Mobility Inventory. The possibility that memory bias
in emotional disorders is a function of basic concern, or functional importance,
rather than positive/negative valence is discussed. The results are also
discussed in terms of degree of elaboration, exposure duration of the stimuli,
and the generality of the findings.
PMID- 9642852
TI - Confirmatory factor analysis of the General Self-Efficacy Scale.
AB - A confirmatory factor analysis of the factor structure of the adapted General
Self-Efficacy Scale, created by Sherer et al. (1982) [Psychological Reports, 51,
663-671], was conducted to assess whether the scale's purported 3 factors
emerged. The results generally supported the 3-factor model, but a model with 3
correlated factors and one higher-order factor (general self-efficacy) proved to
fit the data even better.
PMID- 9642853
TI - Test of Stice's dual pathway model: dietary restraint and negative affect as
mediators of bulimic behavior.
AB - The present study was designed to test whether dietary restraint and negative
affect mediate the relationship between body dissatisfaction and bulimic
behavior. Four hundred and twelve female students completed questionnaires which
measured body dissatisfaction, restrained eating, negative affect and bulimic
behavior. The results indicated that dietary restraint and negative affect
partially mediated the relationship between body dissatisfaction and bulimic
behaviors. The findings are discussed in light of previous research which
suggests that restraint needs to be viewed as a multidimensional construct.
Longitudinal studies are now needed to investigate the causal and possible
bidirectional nature of the interrelationships in the model tested here.
PMID- 9642854
TI - Glove powder--the call for a ban.
PMID- 9642855
TI - Research problems in primary care.
PMID- 9642856
TI - A static diagnosis.
PMID- 9642857
TI - Amalgam tattoo.
PMID- 9642858
TI - Scaling the peaks of private practice.
PMID- 9642859
TI - Anxiety and trauma in the chair.
PMID- 9642860
TI - Short course to an education plan.
PMID- 9642861
TI - Toward a standardised information system for dentistry.
AB - Information technology is growing rapidly in both its capability and capacity to
support the delivery of health care. This paper describes the work of the Dental
Interspec project, commissioned by the Department of Health. The aim of the
project is to provide a framework for the development of information management
and technology in dentistry. It is hoped that the work of this project can be
built on to eventually produce integrated information systems which would have
the potential to improve primary dental care delivery for both patients and
dentists.
PMID- 9642862
TI - Anti-retroviral drugs--implications for dental prescribing.
AB - Many patients with HIV/AIDS are now being treated with two or more drugs to
reduce HIV viraemia and boost CD4 T-cell counts. Patients are using these drugs
earlier in the course of their disease and so GDPs are likely to encounter them
in practice. The drugs have dramatically altered short term prognosis but are
potent and have potentially serious drug interactions. Some of these drugs have
interactions with drugs used in the dental care setting and this paper sets out
to summarise those that are relevant in this area.
PMID- 9642863
TI - The hollow box maxillary obturator.
AB - A case is reported assessing the problems encountered after surgical resection of
the maxilla. The use of a hollow box obturator and details of its construction
are described. The importance of skin grafting of the maxillary defect and use of
available anatomical undercuts to optimise support and retention of the obturator
is stressed. By provision of a lightweight hollow obturator, the weight of the
prosthesis is kept to a minimum, helping retention, and allowing good resonance
during speech. Initially the patient was to be assessed for an implant retained
prosthesis, however, a satisfactory conventional prosthesis met the functional
and aesthetic needs of the patient and avoided the need for further surgery for
placement of implants.
PMID- 9642864
TI - Advances in periodontal diagnosis. 10. Potential markers of bone resorption.
AB - This paper describes the markers of bone resorption which might serve as
potential markers for periodontal disease activity. It firstly describes the bone
specific proteins which are involved in bone mineralisation and the role they
play in this process. It then explains how they may pass into GCF and reviews
those studies which have attempted to relate these factors to periodontal disease
severity and activity. It next discusses the difficulties in isolating and
detecting these factors in GCF and their possible use as markers for periodontal
disease activity. As the final part in the series it lastly discusses the
possible uses of predictive diagnostic tests of periodontal disease activity in
dental practice.
PMID- 9642865
TI - Factors related to time management are major job stressors for GDPs.
PMID- 9642866
TI - Dental treatment for chronically sick children is affected by their medical
disorder.
PMID- 9642867
TI - Allergy to local anaesthetic drugs is rare but does occur.
PMID- 9642868
TI - Perceived sources of occupational stress in general dental practitioners.
AB - AIM: To evaluate levels of occupational stress in general dental practitioners
(GDPs) and compare them with those reported by Cooper et al. (1987).
DESIGN/SETTING: Postal questionnaire in England and Wales. SUBJECTS: A sample of
1007 GDPs was chosen from the Dental Register. MAIN OUTCOME MEASURES: 30 separate
stressors were scored on a 5-point scale. Summated scores within time-, job-,
income-, staff- and patient-related categories were submitted to analysis of
variance by sex, type of practice, years since qualification and geographic
location. RESULTS: 823 questionnaires were returned (82%) of which 667 were from
practising GDPs (63% male, 26% female, 1% undetermined) working full- (87%) or
part- (13%) time in NHS (61%), private (8%), mixed (26%), or community (5%)
practice. In general, problems associated with time management were the most
stressful. The highest ranked individual stressors were 'running behind schedule'
(percentage responding with scores 4 or 5 = 61.9, 95% confidence intervals = 58.2
65.6), followed by 'coping with difficult or uncooperative patients' (58.2, 54.5
61.9) and the 'working constraints set by the NHS' (57.5, 53.8-61.2). Differences
in levels of reported stress (P < 0.05) were observed for at least one group
category of stressor between practitioners with different types of practice,
between males and females, by geographical area (north against south) and by the
length of time since qualification. CONCLUSIONS: The results indicate that GDPs
now rank factors related to time management as major job stressors, with an
apparently dramatic elevation of 'NHS working constraints' to a top-ranking
stressor since 1986.
PMID- 9642869
TI - Comprehensive dental treatment of healthy and chronically sick children under
intubation general anaesthesia during a 5-year period.
AB - OBJECTIVE: To quantify the number of extractions and/or restorations placed in
chronically sick children under intubation general anaesthesia and compare these
findings with healthy children. SETTING: Two large paediatric dentistry units in
Central London: a tertiary referral centre dealing with severe chronic sickness
in children and an undergraduate dental school with a large commitment to special
needs dentistry in children. DESIGN: Prospective comparison of treatment received
for (a) chronically sick children and (b) dentally anxious (otherwise fit)
children receiving intubation general anaesthesia during July 1991 to June 1996
inclusive. The statistical tests used were the Shapiro-Wilks test for normality
and the Mann Whitney U test for non-parametric comparison of independent groups.
MAIN OUTCOME MEASURES: Mean total treatment tally (TTT)--the sum of extractions
and restorations for each child presented as summary data. RESULTS: Different
patterns of dental care were found between the healthy and chronically sick
groups. For similar levels of disease, a significantly greater number of
extractions were carried out for chronically sick children (P < 0.0001), and
significantly fewer restorations (P < 0.0001). The number of pulpotomies and
stainless steel crowns provided to sick children was significantly smaller than
to healthy children (P < 0.0001). This paper discusses the influences of chronic
ill health on dental treatment provided under general anaesthesia. CONCLUSION:
The underlying medical disorder in chronically sick children significantly
influences the pattern of treatment when this is provided under general
anaesthesia.
PMID- 9642870
TI - Alleged allergy to local anaesthetic drugs.
AB - OBJECTIVE: To identify the true nature of an acute reaction in 25 patients
initially diagnosed as allergic to local anaesthetic drugs. SETTING: University
General and Dental Hospitals. INTERVENTIONS: Detailed review of each patient's
previous exposure to local anaesthetic drugs and of the history of the acute
event was followed up with challenge testing by intradermal injection. RESULTS:
One patient was subsequently found to be genuinely allergic to a local
anaesthetic drug of the amide type. A wide range of conditions had actually
precipitated the other adverse reactions, but all could be classified under three
major headings: an immunological condition to a different antigen; a
manifestation of anxiety; or an iatrogenic problem. CONCLUSION: Local anaesthetic
allergy is rare, but does occur. All reactions to local anaesthetic drugs must be
assessed carefully and specialist referral may be appropriate.
PMID- 9642871
TI - The end of the dentist's drill.
PMID- 9642872
TI - [Campylobacter jejuni colitis and Guillain-Barre syndrome].
PMID- 9642873
TI - Doppler velocimetry in the umbilical and middle cerebral arteries in fetuses with
intrauterine growth retardation or fetal distress.
AB - To clarify the usefulness of Doppler velocimetry in high-risk fetuses, i.e. with
intrauterine growth retardation (IUGR) or with fetal distress, nomograms of the
age-related changes in resistance and pulsatility indices in the fetal umbilical
and middle cerebral arteries were made, and the best cut-off values for each
parameter were determined. Included were 505 and 684 fetuses as the control and
subject groups, respectively, between 22 and 41 weeks' gestation. Using the color
coded pulsed Doppler method, the resistance index in the umbilical and middle
cerebral artery (RIUA, RIMCA), the pulsatility index in both these arteries
(PIUA, PIMCA), and the RI and PI ratios between these arteries (RIUA/MCA,
PIUA/MCA) were measured. In normal fetuses, RIUA and PIUA showed a gradual
decrease with advance in gestational age. RIMCA and PIMCA showed a parabolic
fashion with a peak around 30-31 weeks' gestation. RIUA/MCA and PIUA/MCA ratios
decreased until 30-31 weeks' gestation and then increased to term. Analyses with
receiver-operating-characteristic (ROC) curves revealed that PIUA is the most
appropriate parameter in identifying IUGR under the cut-off point of 1.5 S.D.,
with a sensitivity, specificity, positive and negative predictive value, and
accuracy of 60.6%, 93.3%, 75.2%, 87.6%, and 85.0%, respectively. As for fetal
distress, the PIUA/MCA ratio was the most efficacious parameter under the cut-off
point of 2.0 S.D., with a sensitivity, specificity, positive and negative
predictive value, and accuracy of 67.3%, 97.4%, 72.9%, 96.7% and 94.6%,
respectively. The findings obtained indicate that the measurement of PI value in
the umbilical artery is enough to detect IUGR per se, probably due to the
reflection of the decrease in the placental vascular bed, and that the ratio of
indices between the umbilical artery and middle cerebral artery is more accurate
than independent evaluations in identifying fetuses developing fetal distress,
reflecting a brain sparing effect as well as fetoplacental insufficiency.
PMID- 9642874
TI - Indirect measurement of end-diastolic pressure-volume relation in the in situ
canine heart.
AB - We developed a new method to estimate the end-diastolic pressure-volume relation
(EDPVR) of the ejecting ventricle without directly measuring the ventricular
volume. The following equation is derived from the ventricular elastance concept;
Pes = Ees (Ved-Vo-Vj), where Pes is end-systolic pressure; Ees, end-systolic
elastance; Ved, end-diastolic volume; Vo, an empirical constant; and Vj, ejected
volume at end-systole. Therefore, under a constant preload and contractility; two
sets of Pes and Vj, i.e, (Pes 1, Vj 1) and (Pes 2, Vj 2), yield an equation of Ve
= (Pes 1 Vj 2-Pes 2 Vj 1)/(Pes 1-Pes 2), where Ve is effective end-diastolic
volume, Ved-Vo. Repeated measurements of Ve under various levels of end-diastolic
pressure (Ped) allow us to determine the EDPVR. In 8 anesthetized dogs with the
chest open, we obtained two sets of Pes and Vj under a given Ped as mentioned
above, one in a normally ejecting condition and the other in a clamping condition
of the descending aorta to increase afterload of the left ventricle. We then
calculated the Ve from the equation mentioned above. We repeatedly determined the
Ve varying preload levels to obtain the EDPVR. We compared the EDPVR estimated by
the present method with that directly measured by the balloon method in the
arrested ventricle. These two EDPVRs were correlated very well. To compare more
quantitatively, the chamber stiffness constant was obtained. The chamber
stiffness constant derived from the estimated EDPVR was linearily related to that
derived from the directly measured EDPVR (y = 1.043x + 0.003, r = 0.987).
Furthermore, in order to test whether the EDPVR derived from our present method
can detect changes in left ventricular compliance in the in situ ventricle, we
obtained the EDPVRs under the three different (intact, opened, and closed)
conditions of the pericardium in six dogs. The EDPVR was shifted upward in the
closed condition compared with that in the intact condition, while it was shifted
downward in the opened condition. Thus, the changes of the left ventricular
diastolic compliance were correctly evaluated by the developed method. Therefore,
we conclude that the EDPVR obtained using our indirect method is reliable to
estimate the ventricular diastolic properties of the in situ heart.
PMID- 9642875
TI - The canine alkaline phosphatases: a review of the isoenzymes in serum, analytical
methods and their diagnostic application.
AB - This paper reviews the alkaline phosphatases in canine serum, the analytical
methods used for qualitative and/or quantitative detection of these isoenzymes,
and the diagnostic significancy of each of these isoenzymes. The paper further
describes some of the latest advances in our knowledge of the canine alkaline
phosphatases and possible areas of future research.
PMID- 9642876
TI - In vitro viability of mouse oocytes vitrified in an ethylene glycol-based
solution.
AB - Ovulated mouse oocytes denuded of their cumulus cells, were vitrified in a
solution containing 7 M ethylene glycol as the sole cryoprotectant using one or
two steps of exposure before vitrification and were diluted in 1 M sucrose
solution in 5 or 10 min after warming. The results proved that the viability of
oocytes are detrimentally affected by exposure to the vitrification solution even
without vitrification. At 5 min dilution time, the two-step exposure was superior
to the one-step in terms of the post-warming recovery rate of vitrified oocytes
with normal morphology and their subsequent development to the blastocyst stage
(p < 0.01) after fertilization in vitro. At 10 min dilution time, no significant
difference between one- or two-step exposure was found. The effect of the
addition of 0.5 M sucrose to the vitrification solution was also determined and
did not result in a significant improvement in the viability of oocytes vitrified
in one-step and diluted for 10 min. In conclusion, the results in this study
indicate that oocytes can be vitrified with 7 M ethylene glycol as the sole
cryoprotectant in the vitrification solution, and that the recovery of normal
oocytes after one-step exposure in the vitrification solution can be improved by
10 min dilution time. However, the improvement in the recovery rate of oocytes
with normal morphology and their subsequent developmental in vitro was not
improved by the addition of 0.5 M sucrose to the vitrification solution.
PMID- 9642877
TI - Differentiative potential of a mouse parthenogenetic embryonic stem cell line
revealed by embryoid body formation in vitro.
AB - The in vitro differentiative potential of mouse parthenogenetic (PG) embryonic
stem (PGES) cells were investigated in the formation of embryoid bodies (EBs).
EBs derived from PGES cells retarded in growth and showed restricted
differentiation compared to their fertilized counterpart. In chimeric EBs from
the aggregation of PGES and fertilized ES cells, morphological examination
revealed that PGES cells were reduced in their population and distributed in
endodermal layer as culture periods proceeded. These findings were comparable to
those in aggregation chimeras of fertilized and PG embryos, and suggest that the
differentiation of PGES cells in vitro is restricted in the formation of EBs.
PMID- 9642878
TI - Trisomy 8 does not affect differentiative potential in a murine parthenogenetic
embryonic stem cell line.
AB - Murine parthenogenetic embryonic stem (ES) cell lines expressing lac Z reporter
gene were isolated after co-transfection with lac Z reporter gene (pENL) and neo
gene (pSTneo) to TMA-48P cell line of 129/Sv origin. Karyotype analyses showed
that all of four transfected cell lines examined contained 41 chromosomes with
trisomy 8. Bacterial neo transgene required for G418 selection were integrated
into several chromosomes including chromosome 8. Histological studies of
teratomas formed in syngenic mice and embryoid bodies grown in vitro showed that
the differentiative potential remained almost identical in chromosomally normal
parental cell line and its derivative cell lines trisomic for chromosome 8.
PMID- 9642880
TI - Publications by the staff of the Graduate School of Veterinary Medicine.
PMID- 9642879
TI - An introduction of the four departments composing the Graduate School of
Veterinary Medicine, Hokkaido University.
PMID- 9642883
TI - A longitudinal look at the relation between depression and anxiety in children
and adolescents.
AB - Elementary school students (n = 330) and their parents (n = 228) participated in
a 3-year longitudinal study of the temporal relation between anxiety and
depressive symptoms in children. Every 6 months, children and parents completed
depression and anxiety questionnaires for a total of 6 waves. Structural equation
modeling revealed that individual differences on all measures were remarkably
stable over time. Nevertheless, high levels of anxiety symptoms at 1 point in
time predicted high levels of depressive symptoms at subsequent points in time
even after controlling for prior levels of depression symptoms. These findings
were consistent across self- and parent reports. Results support the temporal
hypothesis that anxiety leads to depression in children and adolescents.
PMID- 9642884
TI - Why are depression and anxiety correlated? A test of the tripartite model.
AB - L. A. Clark and D. Watson's (1991) tripartite model groups the symptoms of
depression and anxiety into 3 components: nonspecific symptoms of general
distress, which do not distinguish depression and anxiety; physiologic arousal,
which is relatively unique to anxiety; and anhedonia (or low positive affect),
which is unique to depression. Structural equation modeling was used to test this
model with self-report data from 3 different samples: outpatients seeking
treatment for mood disorder, anxiety disorder, or both (n = 483) outpatients
seeking treatment for substance abuse (n = 453), and college students (n = 516).
The tripartite model did not fit any of the sample covariance matrices, because
the nonspecific symptoms of depression and anxiety could not be adequately
represented by a single General Distress factor. An alternative model, in which
the Anhedonia and Nonspecific Depression factors loaded on a second-order
Depression factor, while the Somatic Arousal and Nonspecific Anxiety factors
loaded on a second-order Anxiety factor, produced an excellent fit in all the
groups. The Nonspecific Depression and Nonspecific Anxiety factors were the most
valid and specific indicators of depression and anxiety, respectively. Anhedonia
and Somatic Arousal were significantly less valid measures of depression and
anxiety. The implications of these findings are discussed.
PMID- 9642885
TI - Temporal progression of alcohol dependence symptoms in the U.S. household
population: results from the National Comorbidity Survey.
AB - General population data are presented on patterns and predictors of temporal
progression of alcohol dependence symptoms in the general population. The data
come from the National Comorbidity Survey, a nationally representative general
population survey of respondents ages 15-54. Lifetime symptom classes were
estimated with latent class analysis (LCA). A 4-class LCA solution, including a
1st asymptomatic class and 3 progressively more serious symptomatic classes, was
found to fit the data. Probability of initial symptom onset among drinkers was
found to be highest in the 10-24 age range, to be higher among men than women,
and to have increased dramatically in the past 4 decades. Age, gender, and cohort
effects were less powerful in predicting symptom progression. A narrowing of the
gender difference over time was due largely to a convergence in initial symptom
onset among men and women ages 10-24. These results suggest that a rise in
initial problems was more important than an increase in the transition from
problems to dependence in accounting for the growing prevalence of alcohol
dependence during the post-World War II years in the United States.
PMID- 9642886
TI - Training in cognitive, supportive-expressive, and drug counseling therapies for
cocaine dependence.
AB - This study assessed the effects of training on the performance of 65 therapists
in delivering manual-guided therapies to 202 cocaine-dependent patients. Changes
in ratings of therapists' adherence and competence was assessed in 3 treatment
modalities: supportive-expressive dynamic therapy (SE), cognitive therapy (CT),
and individual drug counseling. Effects of manual-guided training on the
therapeutic alliance were also assessed. Training effects were examined through a
hierarchical linear modeling approach that examined changes both within cases and
across training cases. A large effect across cases was detected for training in
CT. Supportive-expressive therapists and individual drug counselors demonstrated
statistically significant learning trends over sessions but not over training
cases. Training in SE and CT did not have a negative impact on the therapeutic
alliance, although alliance scores for trainees in drug counseling initially
decreased but then rebounded to initial levels.
PMID- 9642887
TI - Trauma and posttraumatic stress disorder in severe mental illness.
AB - This research assessed the lifetime prevalence of traumatic events and current
posttraumatic stress disorder (PTSD) in 275 patients with severe mental illness
(e.g., schizophrenia and bipolar disorder) receiving public mental health
services in Concord and Manchester, New Hampshire, and Baltimore, Maryland.
Lifetime exposure to traumatic events was high, with 98% of the sample reporting
exposure to at least 1 traumatic event. The rate of PTSD in our sample was 43%,
but only 3 of 119 patients with PTSD (2%) had this diagnosis in their charts.
PTSD was predicted most strongly by the number of different types of trauma,
followed by childhood sexual abuse. The findings suggest that PTSD is a common
comorbid disorder in severe mental illness that is frequently overlooked in
mental health settings.
PMID- 9642888
TI - Autobiographical memory in acute stress disorder.
AB - Survivors of motor vehicle accidents with acute stress disorder (ASD) or with no
ASD participated in a study on autobiographical memory within a week of their
trauma. In Experiment 1, participants were provided cue words to elicit
autobiographical memories of both an unconstrained time period and their trauma.
Participants with ASD reported fewer specific memories to positive cue words than
did non-ASD participants, even when the influence of depression was controlled.
In Experiment 2, the same participants were assessed for posttraumatic stress
disorder (PTSD) 6 months posttrauma. Poor recall of specific memories of the
trauma in Experiment 1 accounted for 25% of the variance of PTSD severity.
Accessibility of trauma memories in the acute posttrauma phase may have
significant implications for longer term adjustment.
PMID- 9642889
TI - The relationship between acute stress disorder and posttraumatic stress disorder:
a prospective evaluation of motor vehicle accident survivors.
AB - Motor vehicle accident survivors (n = 92) were assessed for acute stress disorder
(ASD) within 1 month of the trauma and reassessed (n = 71) for posttraumatic
stress disorder (PTSD) 6 months posttrauma. ASD was diagnosed in 13% of
participants, and a further 21% had subclinical levels of ASD. At follow-up, 78%
of ASD participants and 60% of subclinical ASD participants met criteria for
PTSD. The strong predictive power of acute numbing, depersonalization, a sense of
relieving the trauma, and motor restlessness, in contrast to the low to moderate
predictive power of other symptoms, indicates that only a subset of ASD symptoms
is strongly related to the development of chronic PTSD. Although these findings
support the use of the ASD diagnosis, they suggest that the dissociative and
arousal clusters may require revision.
PMID- 9642890
TI - The Family Health Project: psychosocial adjustment of children whose mothers are
HIV infected.
AB - The psychosocial adjustment of 87 inner-city African American children 6-11 years
old whose mothers were HIV infected was compared with that of 149 children from a
similar sociodemographic background whose mothers did not report being HIV
infected. Children were not identified as being HIV infected. Mother reports,
child reports, and standardized reading achievement scores were used to assess 4
domains of adjustment: externalizing problems, internalizing problems, cognitive
competence, and prosocial competence. The results indicated that, on average,
children from both groups had elevated levels of behavior problem scores and low
reading achievement scores when compared with national averages. Relative to
children whose mothers were not infected, those whose mothers were HIV infected
were reported to have more difficulties in all domains of psychosocial
adjustment. Potential family processes that may explain the findings are
discussed.
PMID- 9642891
TI - Trajectories of adaptation in pediatric chronic illness: the importance of the
individual.
AB - This study used individual growth modeling to examine individual difference and
group difference models of adaptation. The adaptation of 27 children with
juvenile rheumatoid arthritis (JRA) and 40 children with insulin-dependent
diabetes mellitus (IDDM) was tracked for 18 months from diagnosis. A control
group of 62 healthy children was followed over the same time period. Clustering
procedures indicated that child and family adaptation could be described by a
number of distinct adaptation trajectories, independent of diagnostic group
membership. In contrast, parental adaptation trajectory was associated with
diagnostic group membership and control over disease activity for the JRA group
and with diagnostic group membership for healthy controls. The observation of
common patterns across trajectory sets, as well as the finding that trajectories
were differentially related to a number of variables of interest, support the use
of trajectories to represent adaptation to chronic disease.
PMID- 9642892
TI - Factors that mediate and moderate the link between partner abuse and suicidal
behavior in African American women.
AB - Findings from a study comparing partner abuse in African American women suicide
attempters (n = 148) and nonattempters (n = 137) revealed higher rates of
physical and nonphysical partner abuse among attempters than their
demographically similar nonsuicidal counterparts. The partner abuse--suicidal
behavior link was mediated by psychological distress, hopelessness, and drug use
and moderated by social support. Results also revealed that nonphysical partner
abuse accounted for unique variance in the prediction of suicide attempt status
beyond that attributable to childhood maltreatment. Implications of the findings
for assessing both suicidal and abused women are discussed, and recommendations
for preventive interventions for women at risk for suicidal behavior are
provided.
PMID- 9642893
TI - The community reinforcement approach with homeless alcohol-dependent individuals.
AB - Homeless alcohol-dependent individuals were randomly assigned to receive either a
behavioral intervention (i.e., the Community Reinforcement Approach [CRA]) or the
standard treatment (STD) at a large day shelter. Ninety-one men and 15 women
participated. The majority of participants were White (64%), but both Hispanic
(19%) and Native American (13%) individuals were represented as well. Overall,
the decline in drinking levels from intake through follow-ups was significant. As
predicted, CRA participants significantly outperformed STD group members on
drinking measures across the 5 follow-ups, which ranged from 2 months to 1 year
after intake. Both conditions showed marked improvement in employment and housing
stability.
PMID- 9642894
TI - Tailored interventions to communicate stage-matched information to smokers in
different motivational stages.
AB - Smokers in stages of low readiness to quit (immotives and precontemplators) and
smokers in stages of high readiness to quit (contemplators and preparers) were
randomly allocated to 1 of 4 tailored intervention conditions offering outcome
information, self-efficacy-enhancing information, both sorts of information, or
no information. Data on 1,540 smokers, stratified by stage, were analyzed. The
primary outcome measure was stage transition. The hypotheses with regard to stage
matched information for immotives and precontemplators were not verified. With
regard to contemplators and preparers, the following was found: Compared with the
control group, contemplators benefited the most from both sorts of information,
whereas preparers benefited the most from self-efficacy-enhancing information
only. Comparisons between contemplators and preparers who were assigned to the
matched treatment and contemplators and preparers who were assigned to the
mismatched treatment supported these findings.
PMID- 9642895
TI - Interpretive and supportive forms of psychotherapy and patient personality
variables.
AB - A randomized clinical trial investigated the efficacy of interpretive and
supportive forms of short-term individual psychotherapy and the interaction of
each form with the patient's quality of object relations (QOR) and psychological
mindedness (PM). The psychiatric outpatient sample included 144 therapy
completers and 27 dropouts. Eight experienced therapists provided distinct forms
of manual-guided therapy. Outcome was assessed by a comprehensive battery. The
dropout rate was higher for interpretive therapy than for supportive therapy.
Patients in both forms improved, but they did not differ on outcome from each
other. A multivariate interaction effect indicated a direct relation between QOR
and outcome for interpretive therapy and almost no relation for supportive
therapy. A multivariate main effect indicated a direct relation between PM and
outcome for both forms. The relevance of patient personality to outcome in
different forms of therapy is addressed.
PMID- 9642896
TI - Psychopathology associated with sexual abuse: the importance of complementary
designs and common ground.
AB - In their recent longitudinal study of youth victimization and consequent
traumatization, S. Boney-McCoy and D. Finkelhor (1996) contrast their position
with previous retrospective research (S. Harter, P. Alexander, & R. A. Neimeyer,
1988; M. R. Nash, T. C. Hulsey, M. C. Sexton, T. L. Harralson, & W. Lambert,
1993a), arguing that their data support the impact of victimization per se,
independent of the moderating effect of family environment. Because Boney-McCoy
and Finkelhor's argument may misrepresent the results of such studies, this
article (a) clarifies the actual findings of previous retrospective studies of
abuse, (b) suggests methodological limitations both in Boney-McCoy and
Finkelhor's research and in that of S. Harter et al., 1998, and M. R. Nash et
al., 1993a, that should be remedied by future investigators, and (c) argues that
both retrospective clinical research and prospective community surveys converge
on a common ground, namely, that specific abuse experiences can best be
understood and investigated in the context of the prior, contemporaneous, and
subsequent family environments in which they occur.
PMID- 9642898
TI - Brief motivational interviewing in a hospital setting for adolescent smoking: a
preliminary study.
AB - This study tested the feasibility and efficacy of a brief smoking intervention
for adolescents in a hospital setting. Forty adolescent patients were randomized
to receive either brief advice or a motivational interview, a nonconfrontational
therapeutic intervention. Feasibility of brief smoking interventions with teen
patients was supported by high rates of recruitment, retention, and quit
attempts, and long periods of continuous abstinence. Although between-groups
differences on smoking measures were not significant at 3-month follow-up, an
effect size of h = .28 was noted. The sample showed significant decreases in
smoking dependence and number of days smoked. Baseline stage of change, smoking
rate, and depression were significant prospective predictors of smoking outcome.
Implications for smoking intervention research with adolescents are discussed.
PMID- 9642899
TI - Age and drinking-related differences in the memory organization of alcohol
expectancies in 3rd-, 6th-, 9th-, and 12th-grade children.
AB - To advance the theoretical modeling of the development of alcohol expectancies as
a parallel processing memory network, this study assessed expectancies and
alcohol consumption of 2,324 children in Grades 3, 6, 9, and 12 from a large
suburban-rural school district. Individual-differences scaling (INDSCAL), a
variant of multidimensional scaling, mapped expectancies into a hypothetical
memory network format, and preference mapping (PREFMAP) modeled hypothetical
paths of association within this network. Throughout this age range, older and
higher drinking youth appeared to associate positive and arousing effects with
alcohol cues, in contrast to lower drinking children, who appeared to mainly
associate undesirable effects. These drinking-related differences in the
organization of expectancy information are discernible well before onset of
regular drinking habits and may influence the development of drinking in
adolescence.
PMID- 9642900
TI - Posttraumatic stress disorder after treatment for breast cancer: prevalence of
diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening
instrument.
AB - The presence of a posttraumatic stress disorder (PTSD) diagnosis in women (n =
82) diagnosed with Stage 0-IIIA breast cancer was assessed 6 to 72 months after
cancer therapy. The PTSD Checklist-Civilian Version (PCL-C) and the PTSD module
for the Structured Clinical Interview for DSM-IV, Nonpatient Version, PTSD module
(SCID-NP-PTSD) were administered in a telephone interview. SCID-NP-PTSD results
indicated prevalence rates of 6% and 4% for current and lifetime PTSD,
respectively. Use of the recommended cutoff score of 50 on the PCL-C to determine
diagnosis of current cancer-related PTSD resulted in a sensitivity of .60 and a
specificity of .99 with 2 false-negative diagnoses. In conclusion, PTSD can be
precipitated by diagnosis and treatment of breast cancer, and the PCL-C can be a
cost-effective screening tool for this disorder.
PMID- 9642901
TI - Neighborhood social context and racial differences in women's heart disease
mortality.
AB - Compared to white women, black women experience similar rates of heart disease
morbidity, but higher rates of heart disease mortality. This puzzling
relationship may be due to several factors working at varied levels to affect
each race. For example, the high heart disease mortality rate may be due to
individual health or socioeconomic risk factors or to social structural factors.
We conduct a multi-level analysis to address these issues, using data from a
newly released data file that links the National Health Interview Survey with
death certificate information from the National Death Index, and with additional
community level data from the 1990 Census STF-3A files. We are primarily
interested in the effects of female-headship rates in the census tracts on
coronary heart disease mortality (CHD) among black and white women. We find that
women who live in communities with high concentrations of female-headed families
are more likely to die of heart disease, net of other characteristics. For
younger women, the effect appears to be routed primarily through poverty whereas
for older women the effect of female-headship rates remains, net of other census
tract characteristics. This study, then, highlights the importance of examining
the effect of neighborhoods and their social content on mortality.
PMID- 9642902
TI - Athletic participation and sexual behavior in adolescents: the different worlds
of boys and girls.
AB - Using multivariate analysis of covariance to test hypotheses about the effects of
sports and sexual behavior on a sample of 611 Western New York adolescents, this
study concludes that athletic participation and gender interact to influence
adolescent sexual outcomes. Female athletes report significantly lower rates of
sexual activity than female nonathletes; male athletes report slightly (though
not significantly) higher rates than male nonathletes. The gender-specific effect
of sports on sexual behavior remains, net of the impacts of race, age,
socioeconomic status, quality of family relations, and participation in other
extracurricular activities. This paper introduces cultural resource theory to
explain how athletic participation influences both traditional cultural scripts
and exchange resources, which, in turn, condition the sexual bargaining process
and its outcomes for adolescents.
PMID- 9642903
TI - How the negative and positive aspects of partner relationships affect the mental
health of young married people.
AB - The relationship between marriage and positive mental health is one of the most
established findings in the stress literature. Few studies, however, examine the
problematic as well as the supportive impacts of marriage on mental health. This
paper uses a cohort of young adults who were sampled at 18, 21, or 24 years of
age and resampled seven years later when they were married at 25, 28, or 31. It
examines what factors are associated with the quality of marital relationships,
the relative impact of and balance between negative and positive partner
relationships on mental health, and sex differences in the determinants and
outcomes of marital quality. The results indicate that the structural strains of
parenthood and financial need and their interaction predict problematic and
supportive spousal relationships and the difference in the levels of these two
relationships. Problematic relationships with spouses have considerably stronger
impacts than supportive relationships on depression. However, the difference
between the amounts of supportive and problematic relationships with spouses has
a greater impact on mental health than levels of either considered separately.
Finally, relational quality has a greater impact on the mental health of wives
than husbands. These findings indicate the importance of considering how marriage
affects mental health in complex, rather than in straightforward, ways.
PMID- 9642904
TI - Sources and determinants of social support for caregivers of persons with AIDS.
AB - This study examines the determinants of social support among a sample of 642
caregivers of persons with AIDS living in San Francisco and Los Angeles.
Respondents include both traditional family caregivers (mothers, spouses, other
relatives) and non-traditional caregivers (friends, homosexual partners).
Multiple regression analyses are conducted to assess the independent effects of
six sets of variables on emotional and instrumental support: social-structural
factors (age, education, employment status), caregiver's relationship to the
person with AIDS, situational variables (caregiver's HIV status, patient's
functional disability, interpersonal conflict), social network factors (contact
with family, contact with friends, community integration), personal resources
(mastery, caregiving competence), and use of formal community services (patient
directed services, caregiver-directed services). A number of factors and
conditions appear to be relevant for caregiver support. For example, results
indicate that network factors, including frequency of contact, conflict, and
community integration, are importantly related to caregivers' perceptions of
emotional support. There is also a trend suggesting lower emotional support among
traditional family caregivers, relative to nonfamily caregivers, within gender
categories. With respect to instrumental assistance with caregiving, factors that
place greater demands and time constraints on caregivers, such as being employed
and caring for an AIDS patient with greater functional limitations, appear to
increase the level of informal instrumental support the caregiver receives.
Partners and spouses, however, receive significantly lower instrumental
assistance, independent of other factors. Implications of the findings are
discussed.
PMID- 9642905
TI - Relative income expectations, expected malpractice premium costs, and other
determinants of physician specialty choice.
AB - We analyze the effects of relative income expectations, expected malpractice
premium cost, and other economic and noneconomic factors on physician specialty
choice. The data for this paper are taken from responses of medical students who
completed the Association of American Medical Colleges' Medical School
Questionnaire and graduated from medical school in 1995. A random utility model
is used to guide our thinking; the econometric technique is multinomial logit
regression. Selection of a surgical or support specialty is found to be
positively income motivated, while the influence of expected relative income is
negatively related to the choice of primary-care and medical practices. Concern
over malpractice premium cost is negatively related to surgical and positively
related to primary-care selection. Other important determinants of choice are
planned location of practice, length of residency, type of medical school
attended, score on the science problems section of the Medical College Admission
Test, predictable working hours and perceived prestige of the specialty. Policies
that alter expected relative income, length of residency, desired location of
practice, medical school attended, predictable working hours, and prestige of
practice, rather than financial aid, may be appropriate for correcting a
perceived maldistribution of physicians among specialties.
PMID- 9642906
TI - Variability of the center of pressure pattern integral during walking.
AB - The objective of this study was to measure the between-trial variability of the
center of pressure pattern integral (COPPI) at the shoe-floor interface and
within the shoe. Ten trials of the COPPI were recorded simultaneously at the shoe
floor interface and within the shoe as ten subjects walked over ground in
standardized footwear and with two types of foot orthoses. While the results
showed that the within-shoe shoe-only and soft orthoses conditions caused the
greatest decrease in the COPPI, it was extremely inconsistent-between trials,
whether measured at the shoe-floor interface or within the shoe. This suggests
that the COPPI is not an acceptable method of assessing the effectiveness of foot
orthoses.
PMID- 9642907
TI - Foot and ankle injuries among martial artists. Results of a survey.
AB - The practice of the martial arts is associated with a variety of lower-extremity
injuries. Previous studies of the martial arts have examined injuries to the
entire body, while providing only limited information on trauma to the foot and
ankle. After a comprehensive review of the literature on martial arts injuries,
the authors report the results of a survey on foot and ankle injuries sustained
by martial arts practitioners.
PMID- 9642908
TI - Review of the Dockery procedure for lateral ankle instability. A seven-year
retrospective analysis.
AB - This article presents a critical review of the Dockery procedure (autogenous
peroneus longus free graft technique) for the treatment of lateral ankle
instability. Those patients with gastrocnemius equinus were treated with
gastrocnemius recession during surgery. The authors reviewed 33 stabilizations
performed over a period of 7 years to analyze the effectiveness of the procedure
with and without the addition of the gastrocnemius recession. Assessed were the
type and length of conservative therapy, the time to return to regular activity,
complications experienced, and the recurrence rate. The results show a reinjury
rate of 3%. The complications included infection, prolonged healing, and
occasional screw irritation requiring screw removal. In light of the low
incidence of reinjury, this technique is a valid procedure for treating lateral
ankle instability.
PMID- 9642909
TI - Biomechanics of the foot in diabetes mellitus. Some theoretical considerations.
AB - Although diabetes mellitus is a biochemical disease, it has biomechanical
consequences for the lower extremity. Numerous alterations occur in the function
of the foot and lower extremity in people with diabetes. This article evaluates
biomechanical alterations of the foot in the presence of neuropathy in patients
with diabetes in the context of several theoretical concepts. Further study of
these hypotheses will result in a better understanding of how diabetes causes
elevated plantar pressures and the potential of strategies to prevent these
changes so that the burden of diabetic foot disease can be reduced.
PMID- 9642910
TI - Review of radiographic measurements following Austin bunionectomy.
AB - This study compared preoperative and postoperative results for selected
radiographic measurements of 30 patients undergoing the modified Austin
bunionectomy procedure for the correction of hallux abducto valgus. Significant
reductions in all postoperative radiographic values were demonstrated, including
hallux abductus angle, metatarsus primus adductus angle, tibial sesamoid
position, and first metatarsal protrusion distance.
PMID- 9642911
TI - Tarsal coalition in an adult with cavovarus feet.
AB - Symptomatic tarsal coalition is often considered to be synonymous with peroneal
spastic flatfoot. The association of the cavovarus foot type with tarsal
coalition is less well established and has been described only in children. This
article describes a case of an adult female with symptomatic cavovarus feet with
talocalcaneal coalition. The authors theorize about the pathology of muscle spasm
and pain in patients with this condition.
PMID- 9642912
TI - The Ogden Anchor.
AB - Many procedures performed by podiatric surgeons today require the use of a soft
tissue anchoring device. In recent years, many new anchoring devices have become
available for use in the foot and ankle. The authors introduce a new soft-tissue
anchoring device that has yet to be described in the podiatric literature and
present two cases in which the new anchor was used.
PMID- 9642913
TI - Emergence of non-group A streptococcal necrotizing diabetic foot infections.
AB - Recently the authors have noted a disturbing trend toward an increased incidence
of necrotizing infections caused by non-group A streptococcal species. This
article describes the typical clinical course of such an infection. Prompt
surgical intervention, coupled with an antibiotic regimen aimed at mitigating
exotoxin release, may be both limb- and life-preserving.
PMID- 9642914
TI - Vietnamese military shoes then and now.
PMID- 9642915
TI - Complication encountered with self-monitoring of blood glucose levels.
PMID- 9642916
TI - Tibial nerve entrapment and heel pain caused by a Baker's cyst.
PMID- 9642917
TI - The lateral chest radiograph in the detection of pericardial effusion: a
reevaluation.
AB - The purpose of this study was to evaluate the usefulness of 10 previously
published plain film signs for diagnosing pericardial effusion and to determine
whether the posteroanterior (PA) or lateral chest radiograph was the better view
for detecting pericardial effusion. A retrospective study of 100 consecutive
adult patients with pericardial effusions confirmed by echocardiography and/or
computed tomography was undertaken. Five signs were found to be useful in
detecting pericardial effusion on plain films, and the lateral chest radiograph
was found to be better than the PA view in detecting pericardial effusion. The
water-bottle configuration, widening of the carinal angle, and the differential
density sign were helpful in diagnosing pericardial effusion on the PA view.
However, these signs were only seen in moderate-to-large effusions. The displaced
epicardial fat pad sign and the posteroinferior bulge sign on the lateral view
improved the detection of moderate-to-large pericardial effusions, and were also
present in many of the cases with small pericardial effusions. Recognition of
specific signs of pericardial effusion on the lateral chest radiograph may
significantly improve the plain film detection of pericardial effusion.
PMID- 9642918
TI - Bronchial foreign bodies simulating endobronchial malignancy.
AB - Reported are two cases of benign endobronchial lesions with granulomatous
reactions that led to complete airway obstruction. Combined with a long history
of cigarette smoking and the appearance of a hilar mass, these lesions appeared
clinically to be bronchogenic carcinomas. Both cases went to thoracotomy, but in
each case the requirement that malignant tissue be identified, allowed
recognition of a foreign body in one case, and broncholith in the second,
avoiding pneumonectomy in both cases.
PMID- 9642919
TI - Health care for Kentucky's uninsured indigents: the perspective of providers in
the Kentucky Physicians Care program.
AB - The pressing issue of providing care for the uninsured indigent has been
addressed in Kentucky by a unique private sector program that depends on
physician donation of services. The Kentucky Physicians Care (KPC) program which
provides health care to uninsured indigent patients in Kentucky was evaluated
from the perspective of the participating physicians through in-depth interviews
with 22 randomly selected physicians. The results of the interviews suggested
that the KPC program is generally viewed by participating providers as a
successful and personally rewarding enterprise. Suggestions for improving
services included strategies to increase awareness of the program for both
patients and providers. As state and federal policy continues to focus on the
uninsured as a vulnerable population, integration of this private sector program
into a partnership with the public sector may be a worthwhile strategy.
PMID- 9642920
TI - ECG of the month. Plants, catsup.... Artifacts.
PMID- 9642921
TI - Sudden sensorineural hearing loss: etiologies and treatments.
AB - Sudden sensorineural hearing loss of 30 decibels in three contiguous frequencies,
occurring in less than three days, is called sudden hearing loss. Although a
number of disease processes can cause a similar hearing loss, true sudden hearing
loss is idiopathic in nature. This review of sudden hearing loss will focus on
the three main etiologic theories and numerous treatments studied in recent years
in order to better enable clinicians to understand, diagnose, and treat the
disorder.
PMID- 9642922
TI - Radiology case of the month. Painful left hip relieved by salicylates. Osteoid
osteoma.
PMID- 9642923
TI - The journal 150 & 100 years ago. May 1848 and 1898.
PMID- 9642924
TI - Comparison of pediatric hospitalization using the pediatric appropriateness
evaluation protocol at three diverse hospitals in Louisiana.
AB - The purpose of this study was to compare the number of inappropriate pediatric
admissions and hospital days in three hospitals in Louisiana using Pediatric
Appropriateness Evaluation Protocol (PAEP) criteria. The hospitals studied
included an urban, nontertiary care, teaching hospital with 20 inpatient,
pediatric beds (A); a private, tertiary care hospital with 30 beds (B); and a
tertiary care, regional referral center with 133 pediatric beds (C). The study
prospectively observed all nonintensive care pediatric admissions (> six months
of age) between May 1 and June 30, 1993. Admissions and subsequent hospital days
were labeled as appropriate or inappropriate based on PAEP criteria. A
significantly shorter hospital stay (days) was demonstrated at hospital C (4.41
+/- 1.01, p < .05) compared to A (5.98 +/- 4.95) or B (5.78 +/- 1.21). Similarly,
hospital B had significantly more patients admitted electively (19%, p < .05)
compared to A (4%) or C (15%). The percentage of inappropriate admissions for
hospitals A, B, and C were 11.0, 10.0, and 2.0 (p < .05) and hospital days 18.0,
22.0, and 12.0 (p < .05), respectively. A significant proportion of inappropriate
hospital days came from trauma admissions in hospital A (18%, p < .05) and
elective admissions in hospital B (36%, p < .05). Hospital A had 99% of patients
with either Medicaid or uninsured payor status compared to 35% and 84% at
hospital B and C, respectively. Significant differences in the rate of
inappropriate admission or subsequent hospital days were demonstrated in the
three hospitals studied. Finally, the rates of inappropriate hospitalization
demonstrated in this study of Louisiana hospitals were similar to previous
studies using the PAEP in other regions.
PMID- 9642925
TI - A close look at family practice in Louisiana: manpower '97. Louisiana family
practice residency program needs.
AB - There is a shortage of family physicians in Louisiana. This manuscript reports on
the current status of primary care in Louisiana. It compares these data with
national averages and assesses current needs. Finally, it proposes necessary
steps by which this shortage can be decreased. Medical schools, residency
programs, and practicing physicians will need to be involved in the solution to
this problem. Louisiana can have a bright future in family medicine if the
recommendations in this paper are thoroughly addressed. With ever increasing
costs of quality medical care, well-placed funding and emphasis on family
practice appear to be the right direction.
PMID- 9642926
TI - Prolymphocytic transformation of a low-grade lymphocytic neoplasia: chronic
lymphocytic leukemia/lymphoma [corrected].
AB - The clinical case of a patient with a low-grade lymphocytic neoplasia is
presented. The autopsy findings revealing the transformation of the process into
a prolymphocytic dyscrasia are also illustrated. The differential diagnosis is
discussed.
PMID- 9642927
TI - Utility and cost-savings of diagnostic laparoscopy in low-probability gunshot
wounds of the abdomen.
AB - Gunshot wounds of the abdomen are associated with a 90% or greater incidence of
intra-abdominal injury, prompting many trauma centers to routinely explore these
patients via laparotomy. Increasingly, diagnostic laparoscopy has been used to
evaluated the abdomen to exclude peritoneal violation by the missile.
Retrospective analysis of the experience at a Level I Trauma Center with 20
isolated abdominal gunshot wound patients who did not have obvious indications
for laparotomy such as peritonitis or shock is detailed. Outcome and cost
analysis were compared in patients who had diagnostic laparoscopy or laparotomy.
Patients who underwent diagnostic laparoscopy instead of laparotomy had a 42%
reduction in operative time, a 33% reduction in hospital charges, and a reduction
in hospital length of stay from an average of 3.5 days to less than one day. The
only operative complication noted was in a patient who underwent laparotomy.
Diagnostic laparoscopy may be used in select patients to exclude significant
intra-abdominal injuries following gunshot wounds of the abdomen with reduction
in health care costs and morbidity.
PMID- 9642928
TI - [The review of myocardial positron emission computed tomography and positron
imaging by gamma camera].
AB - To measure myocardial blood flow, Nitrogen-13 ammonia. Oxygen-15 water, Rubidium
82 and et al. are used. Each has merit and demerit. By measuring myocardial
coronary flow reserve, the decrease of flow reserve during dipyridamole in
patients with hypercholesterolemia or diabetes mellitus without significant
coronary stenosis was observed. The possibility of early detection of
atherosclerosis was showed. As to myocardial metabolism, glucose metabolism is
measured by Fluorine-18 fluorodexyglucose (FDG), and it is considered as useful
for the evaluation of myocardial viability. We are using FDG to evaluate insulin
resistance during insulin clamp in patients with diabetes mellitus by measuring
glucose utilization rate of myocardium and skeletal muscle. FFA metabolism has
been measured by 11C-palmitate, but absolute quantification has not been
performed. Recently the method for absolute quantification was reported, and new
radiopharmaceutical 18F-FTHA was reported. Oxygen metabolism has been estimated
by 11C-acetate. Myocardial viability, cardiac efficiency was evaluated by oxygen
metabolism. As to receptor or sympathetic nerve end, cardiac insufficiency or
cardiac transplantation was evaluated. Imaging of positron emitting
radiopharmaceutical by gamma camera has been performed. Collimator method is
clinically useful for cardiac imaging of viability study.
PMID- 9642930
TI - [Frameless registration for chest SPECT and X-ray CT image by volume matching].
AB - Image registration of functional (SPECT) and morphological (X-ray CT/MRI) images
has been studied in order to improve the accuracy and the quality of the image
diagnosis. This paper describes a new registration method for chest SPECT and X
ray CT images. Presented method is a frameless and automatic registration method
which calculates a transformation matrix between two coordinate systems of image
data by an optimization method. This registration method uses similar physical
characteristics of X-ray CT and transmission CT image. The three-dimensional
overlap of the body region is used for image matching. Precision evaluation and
visual image evaluation were conducted. The result of the precision evaluation
with a phantom and clinical data suggested the clinically acceptable robustness
in registration procedure. Visual evaluation of registered images confirmed the
usefulness of this method in clinical applications.
PMID- 9642929
TI - [Clinical utility of pulmonary 99mTc-Tetrofosmin uptake measurement by the
exercise myocardial scintigraphy in patients with ischemic heart disease].
AB - Increased pulmonary 201TlCl (Tl) uptake during exercise has been used as a marker
of multivessel critical stenosis. We studied whether pulmonary 99mTc-Tetrofosmin
(TF) uptake measurement during exercise is useful as an additional indicator for
the detection of coronary artery disease. Pulmonary to myocardial uptake ratio
(P/M) measured by TF scintigraphy during exercise were compared with findings of
coronary angiography in eighty one patients with ischemic heart disease and also
P/M measured with Tl in twenty one cases. TF P/M level in the patients with
triple vessel disease was higher than that in the patients with no coronary
stenosis, single vessel disease and double vessel disease. However, there was no
significant correlation between TF P/M and the severity of coronary artery
stenosis. Inverse correlation was observed between TF P/M and left ventricular
ejection fraction (LVEF) (r = 0.29, p < 0.01). TF P/M in the patients less than
50% of LVEF was significantly higher than that in the patients over 50% of LVEF
(p = 0.05). TF P/M was well correlated with Tl P/M (r = 0.86). In conclusion,
quantitative TF P/M during exercise was thought to be useful indicator for the
evaluation of coronary artery disease.
PMID- 9642931
TI - [Regional cerebral blood flow measurements by a noninvasive microsphere method
using 123I-IMP: comparison with the modified fractional uptake method and the
continuous arterial blood sampling method].
AB - A noninvasive microsphere method using N-isopropyl-p-[123I]iodoamphetamine (123I
IMP), developed by Yonekura et al., was performed in 10 patients with
neurological diseases to quantify regional cerebral blood flow (rCBF). Regional
CBF values by this method were compared with rCBF values simultaneously estimated
from both the modified fractional uptake (FU) method using cardiac output
developed by Miyazaki et al. and the conventional method with continuous arterial
blood sampling. In comparison, we designated the factor which converted raw SPECT
voxel counts to rCBF values as a CBF factor. A highly significant correlation (r
= 0.962, p < 0.001) was obtained in the CBF factors between the present method
and the continuous arterial blood sampling method. The CBF factors by the present
method were only 2.7% higher on the average than those by the continuous arterial
blood sampling method. There were significant correlation (r = 0.811 and r =
0.798, p < 0.001) in the CBF factor between modified FU method (threshold for
estimating total brain SPECT counts; 10% and 30% respectively) and the continuous
arterial blood sampling method. However, the CBF factors of the modified FU
method showed 31.4% and 62.3% higher on the average (threshold; 10% and 30%
respectively) than those by the continuous arterial blood sampling method. In
conclusion, this newly developed method for rCBF measurements was considered to
be useful for routine clinical studies without any blood sampling.
PMID- 9642932
TI - [Usefulness of ECG-gated 99mTc-MIBI myocardial SPECT in the follow-up study of
patients with acute myocardial infarction].
AB - To clarify the background of the scintigraphic improvement in non-gated
myocardial perfusion imaging for patients with acute myocardial infarction, we
performed serial ECG-gated 99mTc-MIBI myocardial SPECT in 17 patients with acute
myocardial infarction (AMI) receiving successful reperfusion therapy. ECG-gated
myocardial SPECT and left ventriculography were performed at 1 week (acute phase)
and 1 month (subacute phase) after the onset of AMI. Regional %uptake (regional
count x 100/maximal count) was determined for each of 8 myocardial segments of
the Bull's eye map. We analyzed the data in 53 AMI segments out of total 136
myocardial segments, on the non-gated (NG), end-diastolic (ED), and end-systolic
(ES) images. In addition, the delta %uptake (%uptake in subacute phase--%uptake
in acute phase) was also determined as an index representing the improvement of
myocardial tracer uptake on each image. In 17 segments (group A) with wall motion
recovery assessed by serial left ventriculography, the %uptake on the NG image
was significantly improved (61.6 +/- 10.0 to 75.7 +/- 10.1, p < 0.0001). However,
in 36 segments (group B) without wall motion recovery, the change of %uptake on
the NG image was small. There was no significant change in the %uptake on the ED
image in groups A and B. On the contrary, the %uptake on the ES image showed a
significant increase in group A (58.4 +/- 11.8 to 68.9 +/- 11.8, p < 0.001), but
did not in group B. Thus, this change on the ES image reflects the wall motion
recovery. Furthermore, in group A, there was a significant correlation between
the delta %uptake on the NG image and those on the ES image (p < 0.02), but was
not between those on the NG and the ED images. Thus, the change in the %uptake on
the NG image was more related to those on the ES image which is more affected by
the change in regional wall motion than those on the ED image which reflects
improved myocardial perfusion. These results suggest that ECG-gated myocardial
99mTc-MIBI SPECT is more useful to assess the serial change in myocardial
perfusion and contraction than the conventional non-gated SPECT in the follow-up
study of patients with AMI.
PMID- 9642933
TI - [Prognostic value of myocardial 123I-BMIPP imaging in patients with congestive
heart failure without coronary artery disease].
AB - We performed 123I-BMIPP (BMIPP) imaging in order to clarify the characteristics
of fatty acid metabolism and its effect on prognosis in patients with congestive
heart failure (CHF) without coronary artery disease. We studied 15 normal
subjects and 42 patients with CHF (idiopathic dilated cardiomyopathy; 24,
hypertensive heart disease; 12, valvular heart disease; 6). We obtained cardiac
imaging with BMIPP and 201Tl at rest on separate days before discharge. Using
whole body imaging, the ratio of cardiac uptake of the isotope to total injected
dose was calculated (%Uptake). We calculated the cardiac uptake ratio of BMIPP
(%Uptake of BMIPP divided by %Uptake of 201Tl), percent washout of BMIPP from the
heart over 3 hours and unhomogeneity of myocardial distribution of BMIPP
(coefficient of variation of BMIPP, CV) as scintigraphic parameters. Cardiac
events were defined as cardiac death or deterioration of CHF which requiring
readmission. Uptake ratio (CHF: 0.91 +/- 0.17, normal; 1.10 +/- 0.09, p = 0.0000)
and CV (CHF; 20 +/- 5, normal; 16 +/- 5, p = 0.0385) were different significantly
between CHF and normal subjects. During the follow-up period of 27.2 +/- 14.4
months (4.5-53.5 months) cardiac events developed in 15 patients (cardiac death;
8, deterioration of CHF; 7). In univariate analysis, %uptake of 201Tl, uptake
ratio, % FS, serum norepinephrine level and serum renin activity were different
significantly between event and event-free groups. Cox proportional hazard
analysis showed that the uptake ratio (p = 0.0000) and age (p = 0.018) were
independent predictors of cardiac events. In patients with uptake ratio less than
0.88, relative risks of cardiac events was 23.7 times greater than in patients
with uptake ratio more than 0.89. These data suggested that in patients with CHF
fatty acid metabolism was deteriorated and cardiac uptake of BMIPP was a strong
and independent predictor of long-term prognosis in patients with heart failure.
PMID- 9642934
TI - [Some considerations on the avoidance of excess body burden in case of high dose
131I treatment: with special reference to the urination frequency].
AB - In case of the treatment of metastatic thyroid cancer with radioiodine (131I),
3.7 GBq (100 mCi) or more is often repeatedly administered to the patient.
Therefore, we must be aware of avoiding unnecessary exposure to the radioiodine
except for the lesions to be treated. The administered radioiodine is excreted
mainly through urinary system, resulting in an accumulation of the urine in the
bladder for a certain period, which is highly concentrated with it. Based on this
fact, we set one case having a particular pattern of the whole body retention
curve. Then, two different modes of urination were considered; mode A indicates
every 2 hour-urination x 6 times followed by every 6 hour-urination x 2 times,
and mode B indicates every 6 hour-urination x 4 times. Focusing on the different
amounts of urine in the bladder upon the different modes of urination, the
radiation exposures from the urine to the neighboring organs, such as bladder
wall, uterus, ovary and testis, and also to the whole body were calculated. As
the results, it was found that the urination mode B would cause radiation
exposure from the urine in the bladder twice as much as the urination mode A to
the neighboring organs as well as to the whole body. This study will supply
arguments for the necessity of frequent urination in the cases receiving
radioiodine treatment for metastatic thyroid cancer.
PMID- 9642935
TI - [Epidemiological study on penicillin-resistant Streptococcus pneumoniae].
AB - We studied the differences among clinical isolates of Penicillin-resistant
Streptococcus pneumoniae by polymerase chain reaction (PCR) of pbp2b gene,
followed by serotyping and pulsed field gel electrophoresis (PFGE) analysis.
Clinical isolates were recovered from sputum samples from patients with
respiratory infection in Tottori University Hospital between June 1986 and May
1996. By PCR, altered pbp2b genes of the resistant isolates were detected in
76.5%. The percentages of the isolates that had altered pbp2b genes increased
concomitantly with the minimum inhibitory concentration (MIC). By serotyping the
percentage of 19F, 23F, 6B and 14 was 54.5%, 18.2%, 9.1% and 9.1% respectively.
The frequency of isolates resistant to penicillin increased rapidly from 1991 in
this hospital and most isolates belonged to serotype 19F. The resistant isolates
in this hospital and 4 clinical resistant isolates of S. pneumoniae 19F in a
second hospital were studied by PFGE. 14 of 18 resistant 19F isolates in this
hospital and all 19F isolates from the second hospital presented an identical
pattern. The remaining 4 samples were similar though not completely identical.
These results indicate that the penicillin resistant 19F isolates have a common
clonal origin and have spread rapidly from 1991 in this hospital.
PMID- 9642937
TI - [The role of heat shock protein 60 (HSP60) of Helicobacter pylori in adhesion of
H. pylori to human gastric epithelial cell].
AB - Adhesion of Helicobacter pylori to both human gastric carcinoma cell lines
(MKN45, MKN28 and KATO III) and prepared primary human gastric epithelial cells
were analyzed with flow-cytometry. All strains adhered to human gastric carcinoma
cells. Especially, these strains strongly adhered to MKN45 cells. Adhesion of H.
pylori strains to prepared primary human gastric epithelial cells was also
observed. However, the adherence rates of H. pylori to these cells were different
among the cells used. These results suggested that the host factor might be
important for adhesion of the bacteria to human gasgric cells. In addition, H20
monoclonal antibody directed to H. pylori HSP60 inhibited the adhesion of H.
pylori to both cells. These results indicate that H. pylori HSP60 might be
associated with the adhesion of the bacteria to human gastric epithelial cells.
PMID- 9642936
TI - [Immunization with one dose of inactivated influenza vaccine].
AB - In the winter of 1996, a total of 71 working adults from 20 to 60 (m = 37.3)
years of age were immunized with one or two doses of inactivated influenza
vaccine formulated in Japan. The reciprocal geometric mean hemagglutination
inhibition antibody titers [mean HI] and the percentage with a hemagglutination
inhibition titer of > or = x 128 [percent > or = x 128], against A/
Yamagata/32/89 (H1N1), A/Uhan/359/95 (H3N2), and B/Mie/1/93 were significantly
elevated by either doses. The pre-/post-vaccination mean HI of H1N1 were
61.5/668.4 with one dose, and 85.7/637.3 with two doses. The percent > x 128 were
36.5/96.2 with one dose, and 47.4/94.7 with two doses. No significant differences
were apparent between one and two doses. Similarly, nonsignificant differences
were observed for the other two antigens contained in the vaccine. We observed
the sufficient immune response to only one dose of inactivated influenza vaccine,
which emphasizes the merit of one dose method of influenza immunization.
PMID- 9642938
TI - [Febrile episodes in elderly inpatients--a one year survey to determine the
causes of fever in hospital].
AB - To determine the cause of nosocomial infections, all febrile episodes of
hospitalized elderly patients aged 65 and older at a hospital in Fukuoka City
were categorized between April 15 1994 and April 14 1995. A febrile episode was a
temperature above 37.5 degrees C after 7 consecutive days of normal body
temperature (below 37.5 degrees C). Various clinical tests including blood
examination, urinalysis, chest radiography and bacterial culture were done on the
first and 7th day of the fever. A total of 1105 episodes in 443 patients (male
136, female 307) fulfilled this criteria for fever. The fevers were mainly due to
respiratory tract (381 cases, 34.5%) and urinary tract infections (263 cases,
23.8%). There were 135 infections (12.2%) of other kinds and 297 cases (26.9%)
that were classified as unknown. Approximately 70% of the febrile episodes were
caused nosocomial infections, suggesting increased risk of infection in the
hospitalized elderly and the importance of early detection of febrile changes in
elderly inpatients.
PMID- 9642939
TI - [Shigella dysenteriae strains possessing a new serovar (204/96) isolated from
imported diarrheal cases in Japan].
AB - Five Shigella strains isolated from stool cultures of imported diarrheal cases in
Japan, did not react to any antisera of the established Shigella serovars. These
strains had the typical biochemical characteristics of Shigella dysenteriae, and
were biochemically identical. All strains were positive in the Sereny test and
other tests for invasivness; these indicate that they can cause shigellosis in
humans. The results of antigenic analysis revealed that they did not belong to
any of the recognized or provisional serovars, and were serologically
indistinguishable. They had the same drug-resistance pattern (CP.TC.SM.ABPC.ST)
and plasmid-profile. Strain 96-204 is designated as the test strain for this new
serovar.
PMID- 9642940
TI - Evaluation of two commercial diagnostic kits for Mycobacterium tuberculosis
completely based on bacterial DNA and rRNA amplification for direct detection of
tubercle bacilli in sputum specimens.
AB - The Roche Amplicor Mycobacterium Tuberculosis Kit (Amplicor PCR) and Gen-Probe
Amplified Mycobacterium Tuberculosis Direct Test (MTD) were compared for
efficiency in the direct detection of tubercle bacilli in sputum specimens. In
total, 72 sputum specimens obtained from patients with active tuberculosis were
examined with the Amplicor PCR and MTD kits. Of the 72 test specimens, 45 and 41
samples were positive by the Amplicor PCR and MTD methods, respectively. These
values were larger than those obtained by the culture method (Septi-Chek) and
acid-fast bacilli-smear test, yielding 37 and 20 positive results, respectively,
and the sensitivities were as follows: smear, 39.2%; culture, 72.5%; Amplicor
PCR, 88.2%; MTD, 80.4%. Amplicor PCR was similarly or somewhat more sensitive in
direct detection of M. tuberculosis in sputum samples from patients with
clinically active tuberculosis than was MTD.
PMID- 9642941
TI - [Prevention of Lyme borreliosis infection after tick bites].
AB - Lyme borreliosis is one of the zoonotic and vectorial diseases in the world.
Female of Taiga tick, Ixodes persulcatus play an important role being the main
vector of the agents, Borrelia burgdorferi sensu lato, of the disease in the Far
East including Japan. The number of patients who contacted Lyme borreliosis have
been estimated to be around 100 cases in all of Japan. We also detected the
spirochetes from the skin tissues of 27 cases involving erythema and 3 cases
without erythema after tick bites in Hokkaido. We noticed that in those cases
when the victims removed ticks by themselves using their fingers within several
days later, almost all of them developed erythema. On the other hand, an infected
tick from 8 cases which were removed by surgical procedure, the spirochetes were
not transmitted in these cases (No. 31-38). Therefore, we supposed that the
transmission of agents takes place by regurgitation of the spirochestes from the
midgut diverticula due to the pressure by fingers (calling Syringe phenomenon).
Then, the authors recommended that fine tweezers has a firm grip around the mouth
part of infested tick and pull out within 24 hours and/or trials to surgical
operation for tick removal on passing over 24 hours after infestation.
PMID- 9642942
TI - [Respiratory failure in polymyositis and dermatomyositis: differential diagnosis
between pulmonary infection and interstitial pneumonitis].
AB - Pulmonary diseases are important cause of morbidity and mortality in patients
with PM/DM. Thirteen (27%) out of 49 PM/DM patients in the study had developed
respiratory failure. Respiratory failure resulted form interstitial pneumonitis
(i.p.) in 6, pulmonary infection in 2 and both in 5 patients with PM/DM.
Respiratory failure was fatal in PM/DM patients with pulmonary diseases and
eleven of the 13 patients expired. More importantly, 2 PM/DM patients with
respiratory failure had responded to chemotherapy, if it was due to pulmonary
infection. Accordingly, it is almost important to distinguish i.p. and infection
for the cause of respiratory failure. However, plain chest X-ray as well as
standard laboratory tests failed to differentiate i.p. and pulmonary infection.
On the other hand, high resolution CT of the lungs, serum endotoxin and serum
beta-D-glucan were found to be useful for the differentiation of these conditions
associated with respiratory failure in PM/DM patients. And additionally low serum
level of IgG and lymphopenia at the onset of respiratory failure may suggest that
the patients may have pulmonary infection rather than i.p.
PMID- 9642943
TI - [Experimental studies of polymorphonuclear leukocyte on mandibular bone infection
model in rabbit].
AB - Polymorphonuclear leukocytes (PMN) play important roles in the prevention of
infection at an early stage. We studied the function of these leukocytes using
rabbit models of mandibular bone infection to evaluate the conditions which could
not be reproduced in human beings Streptococcus milleri NCTC7331 and Bacteroides
fragillis NCTC9343 were inoculated into the mandibular bone of rabbits using the
Satoh-Heimdahl method, to produce supposed multiple infection models. Rabbits
inoculated with these bacteria were used as a test group, and animals with
surgically induced inflammation were used as a control group. We compared the
number of leukocytes, the function of PMN, and histopathologic findings. 1) The
number of leukocytes increased after treatment, reached a perk on day 3,
gradually diminished later, but remained slightly higher than the baseline level
on day 7, with persistence of inflammation in both groups. 2) Adhesiveness,
ability to migrate and NBT reduction, were accelerated in both groups. 3) These
functions of PMN accelerated more in the test group because the bacteria
inoculated induced stronger inflammatory reactions and activated a series of
infection defense mechanisms in the hosts. 4) Histopathologic examination after
treatment showed invasion of inflammatory cells, predominantly leukocytes, in
both groups, but heavier and more extensive infiltration in the group treated
with the bacteria. All measurements were higher in the test group than the
control group. These results showed that in the test group, causative or
accompanied microorganisms activated the host's infection defense mechanisms and
accelerated the functioning of PMN at an acute stage of infection.
PMID- 9642944
TI - [Difference of host response in identical toxin-produced Staphylococcus aureus
injected mice].
AB - Biological activities of two strains of Staphylococcus aureus (S. aureus), KU-1
06-37 and KU-1-12-44, which produce enterotoxin type C, TSST-1 and alpha-toxin
were examined using Std:ddY strain mice. These two strains were found to be
different in lethality, ratio of weight loss, induction of leukopenia, adhesion
to surrounding organs and clearance period of bacterial cells from the liver,
kidney and spleen within 24 hrs after intraperitoneal injection in the mice. All
of them were weak or fast in KU-1-12-44 injected mice. Serum amyloid A on all the
KU-1-06-37 and KU-1-12-44 injected mice rose within 5 hr to 18 hr. However, this
concentration of KU-1-12-44 injected mice was about 40% lower compared with that
of KU-1-06-37 injected mice at 21 hr. On the other hand, ability of bacterial
adhesion to established cell lines, Vero and HeLa cells, was tested in vitro.
Percentage adhesion of KU-1-06-37 was high to both cells, but that of KU-1-12-44
was high to Vero cells and was low to HeLa cells. Adhesion of KU-1-06-37 to HeLa
cells that were treated with lipoteichoic acid was about 40% inhibition compared
with untreated cells, although that of KU-1-12-44 to them was inhibited only 9%.
As the results, identical toxin-produced KU-1-06-37 and KU-1-12-44 showed
different biological activities in vivo and in vitro. Not only toxin production
but also adhesion to cells or organs in mice may contribute to S. aureus
virulence to the host.
PMID- 9642945
TI - [Two cases of hematological malignancies diagnosed before death as aspergillosis
with skin lesion].
AB - We report two cases of aspergillosis with skin lesions. The first involved a 63
year-old female with acute lymphocytic leukemia. In 1992, she received
chemotherapy for acute leukemia. Subsequently, she noted swelling of her leg, a
skin biopsy was performed and Aspergillus flavus was isolated. The second patient
was a 71-year-old male with myelodysplastic syndrome. In 1996, he developed a
massive inguinal abscess from which Aspergillus fumigatus was isolated. The
prognosis of aspergillosis was poorer in the case with skin swelling than in the
one with a massive abscess.
PMID- 9642946
TI - [A case of Listeria monocytogenes sepsis in an elderly who survived].
AB - A 81-year-old man who complained of fever and disturbance of consciousness was
admitted to our hospital. Listeria monocytogenes type 1/2aA was cultured from
only the blood. He was treated with gamma-globrine and sensitive antibiotics
(PAPM/BP, EM) immediately after admission, and recovered in spite of multiple
organ failure due to septic shock. He was not an immunocompromised host and did
not have complication of meningitis, but had rhabdomyolysis and liver
dysfunction.
PMID- 9642947
TI - [A case of Kartagener's syndrome associated with pulmonary tuberculosis,
pneumothorax and pulmonary aspergilloma].
AB - A case of Kartagener's syndrome associated with multiple pulmonary complication
was presented. A 19-year-old man was admitted to our hospital because of
pulmonary tuberculosis in May 1972. He had been diagnosed as Kartagener's
syndrome because of the presence of chronic parasinusitis, bronchiectasis and
complete situs inversus. His chest radiographs in Dec 1972 revealed left
pneumothorax. Chest radiographs in Aug 1975 appeared aspergilloma in the right
middle lung field. He was administrated intravenous and oral anti-fungal agent
and transbronchial installation of Amphotericin-B because of hemoptysis. Chest
radiographs in July 1980 resolved the aspergilloma and his symptom were also
resolved. In 1996, he had no pulmonary symptoms and respiratory failure. We
consider that the Kartagener's syndrome was good prognosis with adequate
pulmonary therapy.
PMID- 9642948
TI - [Human parvovirus B19-induced aplastic crisis in a case with spherocytosis].
AB - A 43-year-old female with spherocytosis was admitted to the hospital because of
fever, headache, and rapidly progressive anemia. On admission, she had severe
anemia (Hb 3.9 g/dl) with marked decrease in reticulocytes (0.3%). Some premature
leukocytes, such as promyerocyte, were observed in the peripheral blood. Bone
marrow smear revealed normocellular marrow with normal presence of erythroid
cells. Anti-human parvovirus B19 IgM and IgG antibody was positive in the serum
on admission. The DNA of the virus was also detected in the peripheral blood by
PCR assay. Thus, this case was diagnosed as acute aplastic crisis caused by human
parvovirus B19 infection. Blood transfusion was performed on day 1 and day 2. The
symptoms gradually disappeared and increase in reticulocyte (11.5%) was observed
on day 5. Premature leukocytes in the peripheral blood disappeared on day 2. She
recovered from anemia and was discharged on day 7.
PMID- 9642949
TI - [Pulmonary tuberculosis with diabetes mellitus, presenting multiple nodular
shadows].
AB - An asymptomatic 52-year-old male, who was diagnosed as poorly controlled diabetes
mellitus (DM), was referred to our hospital because of abnormal shadows on chest
X-rays. Physical examinations and laboratory data showed no abnormal findings
except increased values of blood sugar and HbA1c (12.1%). Chest X-ray and CT scan
revealed multiple nodular shadows in both lung fields. The specimens from
transbronchial biopsy showed epithelioid granuloma, and Mycobacterium
tuberculosis was confirmed with bronchial wash fluid. The patient was then
treated with antimycobacterial drugs and sulfonylurea along with diet therapy.
The multiple nodular shadows gradually disappeared. It seemed that impaired host
defense mechanisms caused by poorly controlled DM is responsible for the
bronchogenic dissemination of M. tuberculosis, resulting in the extension into
the multiple nodular shadows. Thus, a good control of DM is important for the
prevention of an onset and excerbation of tuberculosis in patients with DM.
PMID- 9642950
TI - [Surgical treatment of reflux esophagitis and peptic stricture of esophagus].
AB - Reflux-esophagitis is wide-spread and frequently diagnosed disease, which is
found in persons of young and adult age. The main kind of treatment is
conservative one, however sometimes reflux-esophagitis is accompanied by
complications, dangerous for life, which require surgical treatment. Experience
of surgical treatment of 720 patients is available. Fundoplication procedure in
RCS modification combined with SPV is main and optimal operation. This operation
is possible in more than 2/3 cases of surgical treatment of reflux-esophagitis
and peptic stricture of the esophagus. If it is found to be impossible to carry
out organ saving procedure in severe reflux-esophagitis and irreversible peptic
stricture of the esophagus the operation of choice should be extirpation of the
esophagus and gastroplasty with gastric tube or large bowel and simultaneous
creation of anastomosis in the neck. This was carried out in 38 patients with
favourable outcomes.
PMID- 9642951
TI - [Spiral computer tomography in diagnosis of hepatic diseases].
AB - Spiral computer tomography (SCT) is a new method of computer tomography by which,
in contrast to conventional CT, the information about absorptional capacity of
tissues is obtained without omission of images which makes it possible to build
MPR and 3D of a very high quality. 205 patients with diseases of
hepatopancreatoduodenal area were examined, in 189 patients the diagnosis being
verified. Optimal technique of intravenous bolus contrasting in SCT was
developed. Using various time interval between the start of the scanning and the
beginning of infusion of contrast media, it is possible to obtain primary image
of the arteries (arterial phase of contrasting, time of delay 18-25 sec.), the
picture of veins and the image of saturation of hepatic parenchyma--(venous
return phase, time of delay 60-80 sec.), to reveal characteristics of contrasting
of the liver masses during delay (8-15 min) phase. The largest quantity of masses
are revealed in arterial phase of contrasting. Specific features of contrasting
in hemangiomas and malignant tumors of the liver has been revealed. Hemangiomas
absorb contrast medium already at the early phase as hypercontrasted lacunas in
an outlying areas, at a late phase they are hyperdenced in relation to hepatic
parenchyma. Primary and metastatic tumors of the liver accumulate contrast medium
in an early phase along the whole area and quickly lose contrast medium during
parenchymal phase. The method of contrast intensification enables evaluation of
interrelation between tumor and vessels, to determine passage of hepatic arteries
and branches of portal and hepatic veins, to visualise choledochal duct, to
determine the distance between hepatic and tumor surface, and to produce these
data as a view of multiplanar and three-dimensional image (reconstruction). The
effectiveness of obtained reconstructions in planning of the extent of surgical
intervention is demonstrated.
PMID- 9642952
TI - [Diagnosis and treatment of liver echinococcosis complicated by cysto-biliary
fistula].
AB - 890 patients with echinococcosis of the liver were operated during 1976-1992.
Complicated forms of the disease were li detected in 222 (24.9%) patients, among
them 141 (15.8%) patients with cysto-biliary fistulas. Ultrasonography
examination and endoscopic retrograde cholangiography were regarded as the most
informative methods of preoperative diagnosis of cysto-biliary fistulas. Three
stage management was worked out. The usage of laser, plasmatic scalpel and
ultrasound of low frequency substantially contributed to improvement of the
results of treatment of these patients.
PMID- 9642953
TI - [Pre- and postoperative correction of hyposiderosis in surgical treatment of
portal hypertension].
AB - In order to study iron metabolism disorders in patients with portal hypertension
syndrome, to determine clinical significance of hyposiderosis and to work out
effective method of its correction, 94 patients with cirrhosis of the liver
complicated by portal hypertension were examined. As a result of determination of
these disorders of iron metabolism methods for treatment of hypochromal anemia
and hyposiderosis have been worked out. Hemotransfusions, administration of iron
containing preparation Ferrum-lec and combination of these methods were used for
treatment. It was established that administration of large doses of iron
containing preparation Ferrum-lec substantially contributed to improvement of
iron metabolism in patients with cirrhosis of the liver and extrahepatic portal
hypertension, to reduction of postoperative complications rate and to upgrading
the results of surgical treatment.
PMID- 9642954
TI - [Ultrasound diagnosis of acute cholecystitis].
AB - The results of ultrasonographic examination of the gall-bladder in its acute
inflammation in 1070 patients are presented. Parallels between the anatomic
changes and ultrasound visual picture of the inflamed wall of the gall-bladder
were drawn. The analysis of the results of the examination revealed the most
typical symptoms of acute cholecystitis and permitted to differentiate it from
similar ultrasonographic symptoms in other diseases of the gall-bladder. From all
patients who underwent surgical treatment or diagnostic laparoscopy, the
diagnosis was confirmed in 97%. The possibilities of the method in a series of
patients after the operation and patients with concomitant diseases are limited,
in such cases the punction or drainage of the gall-bladder under the ultrasound
scan control for diagnostics and treatment is advisable.
PMID- 9642955
TI - [Roentgenological examination of stomach after pancreatoduodenectomy].
AB - High frequency of complications after pancreatoduodenal resections dictates the
necessity to study causes of their origin. This paper provides the results of
roentgenologic examinations in early and late postoperative periods in 24
patients who underwent classic pancreatoduodenal resection by Whipple and in 23
patients after pylorus saving pancreatoduodenal resection--operation by Traverzo
Longmire. Conventional method of roentgenologic examination of the operated
stomach was used. In early postoperative period disturbances of motor-evacuatory
function of upper parts of gastrointestinal tract were revealed in 50% of
patients in any modification of pancreatoduodenal resection. In most cases
slowering down of the evacuation up to complete gastrostasis was observed. But in
long-term follow-up functional results after pancreatoduodenal resection
according to x-ray examination data were much better after operation by Traverzo
Longmire (75% patients) than after classic version by Whipple (37% patients).
Thus, the results of roentgenologic examination showed that pylorus saving
version of pancreatoduodenal resection provides optimal conditions for normal
activities of the saved organ.
PMID- 9642956
TI - [Lumbar sympathectomy].
AB - Indications for application of lumbar sympathectomy (LS) in chronic arterial
insufficiency of the lower extermities are analyzed. The results of the use of
lumbar chemical desympathisation under computer tomography (CT) control in 10
patients are represented. Prevalences of chemical desympathisation and LS were
revealed which allow us to recommend it for clinical practice.
PMID- 9642957
TI - [Postoperative treatment of retroperitoneal fat suppuration in patients with
gastrointestinal injuries].
AB - Early diagnosis of retroperitoneal festering is possible if methodologically
strictly carrying out of succession of radiation methods (US, computed
tomography, roentgenological examination) is applied and used in complex.
Extraperitoneal approach to phlegmon of retroperitoneal cellular tissue provides
good visualization and is less traumatic. Infusional and enteral therapy in
postoperative period promote effective elimination of volemic disturbances,
stabilization of hemodynamic indices, and provides stable curative effect.
PMID- 9642958
TI - [Early reconstructive-restorative operations in vast traumatic injuries of shin
complicated by purulent infection].
AB - The experience in treatment of 278 patients with extensive traumatic injuries of
the shin complicated by purulent infection is represented. Multistage treatment
typical for such category of patients in which reconstructive-restorative stage
is performed late after elimination of inflammatory process is not optimal. Owing
to the complex of treatment measures based on the principles of active surgical
treatment of festering wounds primary operations were a success in 24.6% of
patients. In 75.4% of patients early dermoplastic and osteoplastic operations
were carried out to 1 month after primary surgical treatment. Good and favourable
results obtained in 98.6% of patients demonstrate effectiveness of the above
policy of treatment.
PMID- 9642959
TI - [Intravascular laser irradiation of blood in treatment of traumatic abdominal
organs injuries].
AB - The application of intravascular laser irradiation of the blood (ILIB) in
combined postoperative intensive care in 28 patients with traumatic injuries of
parenchymal organs and severe intraabdominal bleeding (more than 20% CBV)
contributed to substantial improvement of the results of treatment and reduction
of complications rate. ILIB boosts functional activity of leucocytes, normalizes
the system of hemostasis and antioxidant defence.
PMID- 9642960
TI - [Diagnosis and therapeutic punctures of abdominal organs under ultrasound
control].
AB - Data on 32 diagnostic punctures of the liver, pancreas and spleen under
ultrasonographic US control are available. False diagnosis was registered in 1
case. 16 curative procedures under US control were carried out in patients with
hepatic abscesses (7), suppurative pseudocysts of the pancreas (4), abscesses of
the abdominal cavity (5); in 4 patients external drainage extrahepatic bile ducts
was carried out. This method, being not much traumatic, produces good results in
definite group of surgical patients.
PMID- 9642961
TI - [Wound healing process differences in type I and type II diabetes mellitus].
AB - In 88 patients with purulent wounds in diabetes mellitus the course of wound
healing was studied depending on the type of the disease. Clinical and
morphological distinctions of the wound process in type 1 and type 2 diabetes
mellitus were revealed.
PMID- 9642962
TI - [Liposuction].
AB - Hemostasis was studied in 38 women aged from 24 to 40 years before the
liposuction procedure and 2-3 days after it. The results obtained evidence for
substantial postoperative hypercoagulation changes with simultaneous inhibition
of antithrombine and fibrinolytic activities. Signs of thrombophilic inclination
as a result of hematocrite lowering due to hypervolemic hemodilution. It is
necessary to control hemostasis before the liposuction procedure. The advantage
of hypervolemic hemodilution in prophylaxics of thromboembolic complications is
shown. The category of persons of risk has been determined.
PMID- 9642963
TI - [Psychological, moral-ethic and deontologic aspects of relaparotomy].
AB - Analysis of the results of relaparotomy in 208 patients is presented.
Psychological, moral, ethic and deontologic aspects of repeated laparotomy have
been studied. In indications for relaparotomy the choice of the surgeon is
advisable to make as a collective decision, on individual basis, after careful
analysis of the causes of postoperative complications and with regard for the
wish of the surgeon who performed the first operation. In 137 patients of 208
relaparotomy was carried out by the surgeon by whom the first operation was
performed, with the assistance of more experienced surgeons. Lethality made up
35% (48 patients died after the operation). 60 patients were reoperated by the
other surgeons with the assistance of the surgeon who had carried out primary
operation. In 11 cases relaporotomy was carried out without participation of the
surgeon who had performed the initial laparotomy. 24 (33.8%) patients died after
relaparotomy performed by the other surgeons. "Radical" relaparotomies were
carried out in 141 patients, in 94 (66.7%) of them being performed by the surgeon
who had done the initial operation and in 47 (33.3%)--by the other surgeons. 25
(17.7%) patients died after "radical" relaparotomies and after "palliative"--47
(70.1%) patients. Total lethality after relaparotomy made up 34.6%.
PMID- 9642964
TI - [Saphenoextractor].
AB - New saphenoextractor, including flexible volute-shaped conductor and string
stylet, is proposed and successfully fried. The instrument contains mobile
removable handle with collect as well as a set of olives with collect grip. The
conductor is leaded through the vein's lumen, than the string is introduced into
its lumen and the conductor is withdrawn. The handle is fixed at one end of the
string and the olive--at the other one after which the vein is extracted.
Clinical experience of surgical treatment of varicose veins disease in 105
patients has shown the advantages of the proposed device over other well-known
veinextractors.
PMID- 9642965
TI - [Blood flow measurement in palmar arterial arch of hand and digital arteries].
AB - As a result of examination of 20 healthy people by the method of ultrasound
dopplerography normal values of blood flow in palmar arterial arch of the hand
and digital arteries were established. In the course of examination by this
method of 50 patients with various diseases of arteries of upper extremities
hemodynamically responsible areas for lowering of blood flow were revealed. These
were axileary artery, bifurcation of the brachial artery, both arteries of the
forearm and arterial arch of the hand. Blood flow intensity in the arteries of
the hand and fingers refleds the condition of collateral blood flow in the upper
extremity.
PMID- 9642966
TI - [Management of linea Spigellii hernia in outpatient clinics].
PMID- 9642967
TI - [Cyst of pancreatic head with rupture and profuse bleeding into the lumen of
duodenum].
PMID- 9642968
TI - [Vascular isolation of liver in its vast resections].
PMID- 9642969
TI - [Ernst Bergman (1836-1907)].
PMID- 9642970
TI - Autoimmune causes of recurrent pregnancy loss.
AB - Recurrent pregnancy loss (RPL) is the loss of 3 or more spontaneous and
consecutive pregnancies. There are many causes, such as genetic, anatomic,
hormonal, medical and immunologic causes. Two theories, the alloimmune and the
autoimmune theories, explain the immunologic cause. The Antiphospholipid Antibody
(APA) Syndrome is considered as the autoimmune cause of RPL. It involves two
antibodies, Lupus anticoagulant (LAC) and the anti-cardiolipin antibody (ACA).
The rate of LAC is 7% and of ACA is 15%, among pregnant women. These two
antibodies are believed to cause thrombosis in the maternal circulation, leading
to the events that lead to the fetal losses. Women with these antibodies, along
with other factors, are believed to be at high risk for RPL. The diagnostic
criteria for the APA syndrome include elevated LAC or ACA serum levels and
clinical findings of thrombosis, thrombocytopenia and RPL. Presently, the medical
treatment of the APA syndrome includes heparin, low-dose aspirin, and
immunoglobulins. There must also be an active attempt to search for other causes
of RPL among patients with APA syndrome, such as anatomic, endocrinologic,
anatomic and medical problems. Management of RPL should also include extensive
counseling for the patient and her family.
PMID- 9642971
TI - Prevalence of antibody to Toxoplasma gondii in Hyogo Prefecture, Japan:
comparison at a 10-year interval.
AB - We have previously surveyed antibody to Toxoplasma gondii among Japanese
populations. In this report, we studied the current situation of antibody
prevalence and compared it with the situation approximately 10 years before. A
total of 1,800 human serum samples were collected at the Central Laboratory of
Kobe University Hospital from June through September, 1995, and were examined for
Toxoplasma antibody using enzyme-linked immunosorbent assay. The overall
prevalence was found to be 16.4% with similar seropositivities in males (16.8%)
and females (15.9%). Prevalence of antibody increased with age, reaching 41.0% in
males and 59.0% in females at 80 years or more. Comparison with data obtained at
the same hospital in 1981 to 1982 indicated that seropositivities at 30-39 years
significantly decreased in both males and females. A positivity currently
obtained at a certain age group was similar to a positivity previously obtained
at the corresponding age group (10 years younger), indicating that the previous
age prevalence curve shifted to the current position. A serological survey among
stray cats collected in Hyogo Prefecture in 1990-1991 indicated that 44 (19.0%)
of 231 cats were positive for Toxoplasma antibody as determined by the latex
agglutination test. These results suggested less transmission of Toxoplasma to
humans in Hyogo Prefecture at least for the last 10 years comparing with the
situation in the past, although the transmission cycle among cats was still
active in nature.
PMID- 9642972
TI - Periodic limb movement disorder in neuroleptic-induced akathisia.
AB - We recorded all-night polysomnograms of four schizophrenic patients with
neuroleptic-induced akathisia (NIA) before and during treatment with clonazepam.
Also, four non-akathitic schizophrenic patients were recorded all-night
polysomnograms as control subjects. Daily treatment with 1.5 to 3 mg clonazepam
improved subjective complaints of all the 4 patients with NIA. Three of 4
patients with NIA exhibited periodic limb movements (PLM) on bilateral legs, but
none of 4 control subjects showed PLM. Total number of PLM and PLM per hour
decreased during clonazepam treatment. Moreover, mean inter-movement intervals of
PLM of 3 patients were prolonged on bilateral legs. NIA might change its feature
as PLM during night sleep.
PMID- 9642973
TI - Non-selective cation conductance in a Xenopus renal epithelial line.
AB - The currents activated in single cells of an epithelial cell line from renal
tubules of Xenopus laevis, were studied, using a whole-cell voltage-clamp
technique. After the patched membrane was broken for the whole-cell recording,
the currents developed transiently, reaching a peak in 20 min, in cells held
under voltage-clamp. The currents did not show voltage- and time-dependent gating
behavior at membrane potentials between -100 and +100 mV. The current-voltage
relationships showed strong outward rectification. The ratio of the absolute
amplitude of the current at a potential of +60 mV to that at -60 mV was 24.4 +/-
3.6. The reversal potentials of the currents under various ionic conditions imply
that the membrane conductance was preferentially permeable to cations but that it
had a finite permeability to anions. The cation conductance was non-selective for
monovalent cations and also permeable to Ca2+, with a permeability sequence
(relative to Na+); Na+: K+: Cs+: Li+: Ca2+ = 1.0: 1.3: 1.4: 1.0: 0.7. These
results suggest that in A6 cells, the non-selective cation conductance activated
after the rupture of the patch membrane, may play an important role in epithelial
transport of fluid and electrolyte and that its Ca2+ permeability could be
involved in some physiological signal transduction.
PMID- 9642974
TI - Airway lesions and superoxide dismutase (SOD) distribution in bronchopulmonary
dysplasia (BPD).
AB - We examined 71 cases of bronchopulmonary dysplasia (BPD) at autopsy and divided
them into five groups on the basis of the patients' survival time, studying on
the histological changes in the airways for the purpose of clarifying the
pathogenesis of BPD from hyaline membrane disease (HMD). Furthermore, bronchiolar
occlusion was classified into four types: secretion, obliterative bronchiolitis,
intraluminal plug, and hyperplasia of bronchiolar components. The same occlusive
findings as in bronchioli and hyaline membrane were observed from respiratory
bronchioles to alveolar ducts. However, there was no obvious correlation between
airway lesions and accompanying alveolar lesions excepts three cases of
obliterative bronchiolitis. Furthermore, immunohistochemical studies with anti
human SOD antibodies were performed. Mn-SOD was positive for alveolar macrophages
in longer surviving infants without significant correlation with histological
variation, whereas slightly positive or negative in infants who died within 1
week; CuZn-SOD was rarely positive in any cases. These results is highly
correlated to the pathogenesis of BPD and to its pathological advancement with
its clinical course.
PMID- 9642975
TI - The legal/ethical mix.
PMID- 9642976
TI - Risk management and the Dental Practice Act.
PMID- 9642977
TI - Get rid of the dental garbage.
PMID- 9642978
TI - Survival of the profession.
PMID- 9642979
TI - Valuable information.
PMID- 9642980
TI - Certified dental assistants. Dentistry's newest professional category.
PMID- 9642981
TI - Dentistry and malpractice. Looking back on 13 years.
PMID- 9642982
TI - DSSNY course bolsters dentists' defenses.
AB - The DSSNY risk management course was born of crisis. Now in its fifth version,
the course is credited with increasing competition among malpractice carriers and
lowering premium prices.
PMID- 9642983
TI - Risk management and the claims process.
AB - This article explores certain risk management techniques and the role these
techniques play in the investigation and evaluation of claims. The claims
experience of one carrier, Medical Liability Mutual Insurance Co., is provided. A
general overview of the elements involved in a claims investigation is provided.
PMID- 9642984
TI - For the record. Understanding patient recordkeeping.
PMID- 9642985
TI - [Extracellular matrix and hepatobiliary surgery].
PMID- 9642986
TI - A clinical study of elderly patients with acute cholecystitis.
AB - In recent years, an increase in average life expectancy has led to a rapid rise
in the number of elderly patients undergoing surgery for acute cholecystitis. We
studied the clinical characteristics of elderly patients (aged 75 years of more)
undergoing surgery for acute cholecystitis, as compared with those of non-elderly
patients (aged less than 75 years) undergoing similar procedures. Twenty-four of
the patients were elderly, and 44 were non-elderly. RESULTS: Echography and
abdominal computed tomography (CT) revealed no characteristic findings specific
to elderly patients, but a smaller proportion of elderly patients showed a three
layered structure of the gallbladder wall. The leukocyte count on admission was
significantly lower in elderly patients than in non-elderly patients. As for
therapy, a significantly higher proportion of elderly patients underwent
percutaneous transhepatic gallbladder drainage (PTGBD) + cholecystectomy +
choledochotomy/choledocholithotomy, as compared with non-elderly patients. In
contrast, cholecystectomy alone was performed more frequently in non-elderly
patients than in elderly patients. The main postoperative complications were
psychic symptoms and respiratory tract infections. The postoperative hospital
stay was significantly longer for elderly patients, in part because they
requested to remain in the hospital until they were able to perform activities of
daily living.
PMID- 9642987
TI - A case of early gastric carcinoma with acute gastric mucosal lesions presenting
difficulty in differentiating advanced gastric carcinoma.
AB - An 87-year-old man diagnosed as having advanced gastric carcinoma was admitted to
our hospital. In a barium X-ray examination of the stomach taken at another
hospital, filling defects were obseved in the greater and lesser curvatures of
the antrum, while the entire pyloric region was rigid and stenotic. The
gastroscopic findings showed pronounced curvature and stenosis of the pylorus and
the pyloric mucosa was edematous and sclerotic. Histopathological examination of
a biopsy specimen from the pylorus indicated a group V. The gastroscopic findings
subsequent to admission displayed pronounced improvement with only sporadic
shallow ulceration and erosion. The histopathological findings of the excised
specimen showed that several depressed lesions in the antrum were active ulcers
or their scars and the depressed lesions extending from the antrum to the pyloric
ring were early gastric carcinoma. The findings of filling defects of the antrum
and stenosis with ridigity of the pyloric region in the radiographic examination,
and pronounced curvature and stenosis of the pylorus and sclerosis with edema of
the pyloric mucosa in the gastroscopic examination were very similar to typical
findings of advanced gastric carcinoma with pyloric stenosis. In addition,
histopathological examination of a biopsy specimen from the pylorus indicating a
group V made differentiation from advanced gastric carcinoma extremely difficult.
PMID- 9642988
TI - [Pathologic features of acute allograft rejection in ABO-incompatible renal
transplantation].
AB - BACKGROUND: In order to examine the difference in histological findings during
acute rejection between ABO-incompatible renal transplantation and compatible, we
studied biopsy specimens from renal allografts histopathologically. METHODS:
Twenty one ABO-incompatible cases (ICBG) and fifteen compatible cases (CBG) who
were transplanted at Tokyo Women's Medical College and considered to have acute
rejection clinically were selected. Lightmicroscopic findings classified Banff
schema, deposition of globulins and complements, expression of HLA class II
antigen (DR) and adhesion molecules (ICAM-1, VCAM-1), subset of infiltrating
cells, blood type antigen and specific antigen for endothelium (Thrombomoduline:
TM, Factor VIII) were compared between CBG and ICBG on biopsy specimens. RESULTS:
Tubulitis was observed in 71.4% of ICBG and all cases of CBG. Severe interstitial
infiltration of CD8 positive cells and polymorphonuclear leucocyte (PMN)
glomerular infiltration was showed in 52%, 85.7% of ICBG and 100%, 0% of CBG. The
incidence of fibrinogen deposits was 47.6% in ICBG and 26.7% in CBG. Tubular
expression of DR, ICAM-1 and VCAM-1 were positive in 25%, 40%, 45% of ICBG and
91.7%, 100%, 100% of CBG. Monoclonal antibody for TM was demonstrated more
strongly positive in CBG (73.3%) than in ICBG (28.6%). These findings had
significant differences in ICBG from CBG. CONCLUSIONS: Acute rejection of ABO
compatible renal transplantation was characterized by tubulitis accompanied by
high expression of DR, ICAM-1 and VCAM-1, which subsequently injure tubulo
interstitium. On the other hand, ABO-incompatible acute rejection showed
endothelial injury characterized by fibrinogen deposition and severe PMN
infiltration in glomeruli (glomerulitis).
PMID- 9642989
TI - [Regional lymph node metastasis in renal pelvic or ureteral cancer].
AB - BACKGROUND: The objective of this study is to evaluate the frequency of regional
lymph node metastasis, clinical outcomes and histopathological findings of renal
pelvic or ureteral cancer with regional lymph node metastasis. PATIENTS AND
METHODS: One hundred and sixty three patients with renal pelvic or ureteral
cancer were treated in our hospital between 1961 and 1995. Eighty nine in 155
patients underwent lymph node dissection. Frequency of regional lymph node
metastasis, clinical outcomes and histopathological findings of these 89 patients
were investigated. Patient survival rates were determined by actuarial
calculation using Kaplan-Meier method with log-rank test. RESULTS: The status of
lymph node involvement was pN0 in 61 (68.5%), pN1 in 5 (5.6%), pN2 in 15(16.9%)
and pN3 in 8 patients (9.0%). The 5-year survival rate was 78.8%, 12.5%, 20.0%
and 0% for pN0 pN(+), pN1, pN2 and pN3 respectively. In 28 patients with regional
lymph node metastasis, patients with distant metastasis were all dead within 1.2
years and the 3- or 5-yer survival rates of patients without distant metastasis
were 31.4% and 15.7%. The difference between two groups were obvious (p < 0.01).
The 3-year survival rate was 100%, 66.7%, 33.3% and 0% for pT1, pT2, pT3 and pT4
patients with M0 and pN(+) respectively. CONCLUSION: Our data suggested that
conventional treatments were not effective for almost patients with regional
lymph node metastasis. However in the patients with low grade, under pT3 and M0,
pN1-2, the possibility of long time survival was shown.
PMID- 9642990
TI - [Immunohistochemical analysis of expression of angiogenic factors and tumor
angiogenesis in superficial bladder cancer].
AB - PURPOSE: We evaluated expression of angiogenic factors, tumor vessel density and
recurrence in superficial bladder cancer by immunohistochemistry. METHODS: Fourty
tumor specimens from bladder preserving operation and 11 normal epithelia were
stained for factor VIII-related antigen, vascular endothelial growth factor
(VEGF), basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor
(aFGF). Maximum vessel density (MVD) was counted in a 200x field in the highest
vascularized area stained for factor VIII. Superimposing a 4 x 4 square ocular
grid on the boundary between epithelium and interstitium, average vessel density
(AVD) and vascular surface density (VSD) were calculated by dividing the vessel
number in the grid and the intersection number of vessel walls on the lattice
lines by the area of interstitium calculated from the number of the gird cross
points, respectively. RESULTS: Positive rates of VEGF, bFGF and aFGF by
immunohistochemistry were 50%, 23% and 43% in the superficial bladder cancer,
respectively. The positive rate of VEGF staining was higher in G2-3 tumors than
in G1 tumors. All normal epithelia, except one which was positive for aFGF, was
negative for those three factors. T1 tumors had a higher MVD than that of Ta. AVD
and VSD of the tumor were higher than those of normal epithelium, but negative
correlation between the number of positive angiogenic factors and the vessel
density was revealed. The recurrence group had a lower vessel density and a
higher ratio of VSD/AVD than those of the non-recurrence group. CONCLUSION: These
findings suggest that the expression of VEGF, bFGF and aFGF was not reflected by
the tumor angiogenesis, the angiogenesis is required topically at the invasive
front of the superficial bladder cancer, and the tumor which had fewer and
broader tumor vessels has a high tendency to recur.
PMID- 9642991
TI - [A study of the differences between the sexes in epidemiology of urolithiasis].
AB - PURPOSE: Uroithiasis seems to be the dominant disease for male. In the recent
Japanese epidemiological report, the sexual ratio was reported 2.3:1. This sexual
ratio is almost stable from 1960. We studied epidemiologically based on age and
stone components the differences between the sexes. PATIENTS AND METHOD: From
1977 to 1996 the upper urinary tract stones which spontaneous excretion or
surgical removal in our hospital were the subjects of study, Stone analysis was
carried out infrared spectrometer. The statistical analyses were performed by the
chi-square test and Mann-Whitney's U test. Significance was declared for a
probability value of less than 0.05. RESULTS: In the epidemiology of our treated
patients sexual ratio was 1.83:1. We studied sexual ration in age and stone
components. The sexual ratio of the patients, 60 years and over was decreased
compared with that of the patients under 60 years of age. We found the tendency
that the sexual ratio was decreased at 60 years old and over. In the female
urolithiasis patients less than 60 years old the frequency of calcium oxalate
contained stone patients was predominantly smaller than male. In the female
urolithiasis patients of 60 years and over the stone component ratio was similar
to male urolithiasis patients. CONCLUSION: In point of frequency sexual ratio was
decreased at 60 years old and over. In the female patients less than 60 years old
the frequency of calcium oxalate contained stone was predominantly small. This
low frequency of calcium oxalate contained stone in the female less than 60 years
old seemed to be a factor of the sex differences of frequency.
PMID- 9642992
TI - [Tumor volume and percent of gland involvement with tumor as predictors of
pathological stage in prostate cancer].
AB - BACKGROUND: It is well recognized that tumor volume correlates with pathological
stage, histological grade and progression in prostate cancer. We analyzed the
tumor volume and the percent of gland involvement with tumor (%TV/PV) to
determine if either or both of these morphometric factors would be good
predictors of pathological stage. METHODS: The pathological reviews were
retrospectively performed on the basis of the 22 step sectioned prostate
specimens removed by radical retropublic prostatectomy for clinical T1c-T2-T3
prostate cancer. The percent of gland involvement with tumor was calculated using
the following formula [100 x (tumor volume cc/prostate volume cc)]. When the
patients had organ confined disease (OCD) or specimen confined disease (SCD) they
were defined as surgically cured patients, whereas the patients with positive
surgical margin, seminal vesicle involvement or positive lymph node were defined
as not surgically cured patients. RESULTS: The likelihood of OCD was 25% in
patients with clinical T1c-T2 disease. No patients with clinical T3 had OCD.
Patients with SCD was not observed. The mean tumor volume was 1.3 cc in the
surgically cured patients and 6.2 cc in the not surgically cured patients. The
tumor volume correlated with pathological stage (r = 0.607, p = 0.0054). The mean
%TV/PV was 3.23% in the surgically cured patients and 18.2% in the not surgically
cured patients. The %TV/PV also correlated with pathological stage (r = 0.543, p
= 0.0129). Both the tumor volume and the %TV/PV in surgically cured patients were
less than those in the not surgically cured patients. A correlation between tumor
grade and both the tumor volume and the %TV/PV were not observed. CONCLUSION: The
tumor volume and the %TV/PV correlated well with the final pathological stage.
Multiple regression analysis showed that the tumor volume was the best predictor
of pthological stage.
PMID- 9642993
TI - [Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis].
AB - BACKGROUND: Radiation therapy has widely been used for cancers in the pelvis.
Radiation cystitis, one of the late complications, presents often as hemorrhagic
cystitis, which is refractory to the conventional therapy and may threaten the
patient's life. We used hyperbaric oxygen therapy on patients with radiation
cystitis to test its potential benifit. METHODS: Ten patients aged from 46 to 81
years with a mean of 62 years underwent one or more courses of hyperbaric oxygen
therapy according to their symptoms, consisting of 20 sessions (3 to 5 sessions a
week) at the Department of Hyperbaric Medicine, the University of the Ryukyus
Hospital in the 9-year period from 1985 to 1994. They included 8 patients having
a history of cervical cancer, one with external genital cancer and one with
vaginal cancer. During the 75 min hyperbaric oxygen therapy patients received
100% oxygen at 2 absolute atmosphere pressure in the Multiplace Hyperbaric
Chamber. RESULTS: Hematuria subsided and subjective symptoms including urinary
frequency improved in seven patients. Cystoscopic findings including mucosal
edema, redness, and capillary dilation were partially improved. The procedure
subjectively and objectively palliated the 10 patients in a favorable manner.
CONCLUSIONS: To date we have not armed any active procedure to control radiation
induced refractory hemorrhagic cystitis in terms of efficacy, invasiveness, and
adverse effects. Therefore, in consideration of our clinical results, hyperbaric
oxygen therapy appears to be useful for radiation cystitis.
PMID- 9642994
TI - [Renal malignant lymphoma: report of a patient surviving 17 months without
recurrence and review of 43 Japanese cases].
AB - A case of renal malignant lymphoma is reported. A 74-year-old man was admitted to
our hospital on September 8, 1995, complainning of right flank pain, abdominal
mass, and anorexia for two months. Physical examination revealed an enlarged
right axillary lymph node and abdominal mass of child's head size. Computerized
tomography showed a tumor (11 x 7 cm) encompassing the right kidney parenchym,
and enlarged paraaprtoc lymph nodes with invasion of the left iliac creat.
Transcutaneous echo-guided needle biopsy revealed that the tumor was non
Hodgkin's malignant lymphoma, diffuse large cell type, positive for B cell
marker. The patient was treated with full dose of CHOP regimen. However,
adriamycin was replaced with pirarubicin and the dose of the other drugs were
reduced for the subsequent 4 courses because of severe leukocytopenia,
thrombocytopenia, hepatotoxicity, and alopecia after the first course of the
treatment. The patient showed complete remission and discharged on March 12,
1996. He, after 17 months, has no signs of recurrence. We reviewed 43 Japanese
cases previously reported as renal malignant lymphoma. It is increasing in Japan
especially in elderly. The 2-year survival is 26.6%.
PMID- 9642995
TI - [A case of metastasis to the seminal vesicle of renal cell carcinoma].
AB - A case of metastasis to the seminal vesicle of renal cell carcinoma is reported.
A 60-year-old man was referred to our department for evaluation of intermittent
hematospermia and asymptomatic macrohematuria for about 2 years. He had a left
radical nephrectomy for localized renal cell carcinoma 5 years ago. Panendscopy
showed a little bleeding of posterior urethra, but there were no abnormal images
of upper urinary tracts. Two years later he had asymptomatic macrohematuria again
and panendscopy showed swelling and bleeding of verumontanum. Transurethral
resection of verumontanum revealed clear cell carcinoma histopathologically and
CT revealed seminal vesicle or prostate tumor, then total cystectomy was
performed. Pathological examination indicated metastasis to siminal vesicle of
renal cell ccarcinoma. There has been no report of metastasis to seminal vesicle
of renal cell carcinoma in literature. This is the first case in the world.
PMID- 9642996
TI - [Primary adrenal schwannoma].
AB - We report a rare case of retroperitoneal schwannoma arising from left adrenal
gland. A 45-year-old man with upper abdominal discomfort was found to have a
tumor in the left adrenal gland by abdominal ultrasonographic scan. The
laboratory findings were all normal but angiogram indicated slightly
hypervascular adrenal tumor. Eventually, he was underwent left adrenalectomy. The
removed mass was measured 6.5 x 5.7 x 5.0 cm and weighed 75.5 g. Pathological
study revealed benign schwannoma arising from the adrenal gland, consisting
mainly of the Antoni A type. A review of the literature on adrenal schwannoma is
included.
PMID- 9642997
TI - [Retropharyngeal node metastasis in cancer of the oropharynx and hypopharynx:
analysis of retropharyngeal node dissection regarding preoperative radiographic
diagnosis].
AB - In our department, all patients with advanced carcinoma of the oropharynx and
hypopharynx are treated by retropharyngeal (RP) node dissection in addition to
primary resection and standard neck dissection. Records of 42 patients (11
oropharynx, 29 hypopharynx and 2 retromandibula) who received RP node dissection
from 1992 to 1996 in our department were examined for metastasis to RP nodes and
for preoperative radiographic diagnosis (MRI or CT). The criteria for
radiographic involvement of RP nodes are as follows: a diameter greater than 10mm
on axial images or central necrosis within the nodal substance. Of the 42
patients, 6 (14.3%) had pathologically positive RP nodes and of those 6 patients,
5 were able to be diagnosed preoperatively by either CT scan or MRI. Results of
radiographic diagnosis (MRI or CT) were as follows: by CT scan the sensitivity,
specificity and accuracy were all 100% and by MRI the sensitivity, specificity
and accuracy were 83.3%, 100% and 97.0% respectively. It is our conclusion that
preoperative radiographic diagnosis (MRI or CT) is very useful and effective for
diagnosis of metastasis to RP nodes.
PMID- 9642998
TI - [Clarion 16 cochlear implant (System introduction and use experience in Japan].
AB - The Clarion cochlear implant was developed in the USA and received FDA approval
in August 1996. It consists of an implantable cochlear stimulator (ICS), speech
processor with headpiece, and in addition, a clinician's programming system and
portable cochlear implant tester. One of the features of the device is its
stimulation-coding process for which two methods of continuous interleaved
sampling (CIS) and compressed analogue (CA) are applicable. Regardless of which
is used, stimulation can be provided over 8 channels. The device was used in 2
cases. Both patients were operated on in October 1996, and 16 electrodes in 8
pairs were mounted in the cochlea. Mapping, performed 3 weeks after the
operation, showed good speech perception in both patients with only a cochlear
implant in the "open-set" status. CIS was used as the stimulation-coding method.
CA has yet to be applied.
PMID- 9642999
TI - [Result of treatment of squamous cell carcinoma of the tongue and floor of the
mouth].
AB - A statistical analysis was performed on 40 patients with squamous cell carcinoma
of the tongue and mouth floor, which could be followed for 6 months or more after
initial treatment in the Department of Otorhinolaryngology, School of Medicine,
Keio University during the 14 years from 1983 to 1996. The 5-year survival rate
determined by the Kaplan-Meier method for each stage was 100% for Stage I, 77.8%
for Stage II, 60.0% for Stage III and 44.4% for Stage IV. Thirteen suffered a
relapse after initial treatment and patients with relapses among them have all
survived after the subsequent salvage surgery. In contrast, in nine patients with
cervical relapse, however, the 5-year survival rate was 11.1% with an unfavorable
prognosis. This confirmed that suppressing cervical relapses is important for
treating tongue and floor mouth cancers. The treatment strategy in our department
is characteristic of positive enforcement of prophylactic neck dissection in the
surgery and introduction of neoadjuvant chemotherapy (NAC) in the chemotherapy.
Prophylactic neck dissection was performed in the 17 patients and no relapse was
observed on the side of prophylactic neck dissection. NAC was performed on 26
patients in consideration of suppressed minute metastases and preserved function
and 24 determinable cases were statistically analyzed. Among patients who had
received NAC, the oral function was successfully preserved without surgical
intervention in six patients both patients who showed complete response (CR) and
four out of 14 patients who had a partial response (PR) following NAC. This may
indicate that the oral function could be preserved in those patients who
exhibited CR following NAC, but that preservation could be difficult in patients
who exhibited PR. In addition, concerning the accumulated 5-year survival rate in
relation to the effect of NAC, responders (CR + PR) accounted for 90.9% and non
responders (no change + progressive disease following NAC) for 15.0% with a very
good outcome noted in the responder group. These figures suggest that responders
may have a significantly good prognosis in the multivariant analysis including
additional background factors before treatment as well. Accordingly, the present
therapeutic measures for non-responders must be reexamined and performed more
carefully and accurately as compared with those for responders.
PMID- 9643000
TI - [An immunohistochemical study of RB tumor suppressor gene protein and bcl-2 gene
protein in carcinomas of the thyroid gland].
AB - The expression of RB and bcl-2 proteins was investigated in 135 thyroid
carcinomas (130 papillary carcinomas and five follicular carcinomas) by the
immunohistochemical technique with RB and bcl-2 monoclonal antibodies. The
results were as follows: 1) RB protein nuclear staining was shown in 117 of the
135 thyroid carcinomas (87%). Bcl-2 protein staining was shown in 82 of the
carcinomas (61%). 2) There was a higher incidence of recurrence in RB-negative
cases than in RB-positive cases (chi 2 test p = 0.001). But there is no
significant relationship between the incidence of recurrence and the results of
bcl-2 staining (chi 2 test p = 0.287). 3) The expression of RB protein was
related to age and clinical N and M categories. Bcl-2 protein expression was
related to clinical T categories. 4) The 10-year overall survival rate for RB
positive patients was higher than that for negative patients (long-rank test p <
0.0001). But the survival rate was not associated with bcl-2 expression (log-rank
test p = 0.3). Our results suggest that assessment of RB protein expression by
the immunohistochemical technique may be useful to determine the possibility of
recurrence and to predict the outcome of thyroid carcinomas. We think that
assessment of RB protein expression by the immunohistochemical technique can be
applied as a more sensitive prognostic factor.
PMID- 9643001
TI - [Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate
analysis of prognostic factors and evaluation of therapeutic modalities].
AB - Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at
Keio University Hospital between July 1981 and June 1996 were reviewed
retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old,
with an average age of 62.7. The primary lesion was located in the lateral wall
in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14
(15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21
patients (23.1%). The patients were divided into two groups according to the
initial main treatment of the primary lesion without regard to chemotherapy: 72
patients (79.1%) who received curative radiotherapy with or without salvage
surgery, and 14 patients (15.4%) who underwent curative surgery with or without
preoperative and/or postoperative radiation. The remaining 5 patients were
treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%)
received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by
the Kaplan-Meier method as univariate analysis, and compared by the generalized
Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five
year survival rates according to stage (UICC classification, 1987) were as
follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30
cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological
variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p =
0.0274); and (3) location of primary lesion (p = 0.0400). The results of
multivariate analysis by Cox's proportional hazards model identified T stage as a
significant independent prognostic factor. Evaluation of the therapeutic
modalities led to the following conclusions. (1) Differences in the initial
treatments of the primary lesion were not reflected in the outcome. (2) Salvage
surgery for residual or recurrent tumor contributed to improving the survival.
The superior wall type, in particular, seemed to be a good indication for salvage
surgery. (3) Although the limitations of radiotherapy are not defined clearly, we
have to determine the indications for radical resection of tumors resistant to
radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but
there were no significant differences in survival between the group that
underwent NAC and the other group in any other subset analyses. (5) Among the
patients who underwent NAC, the responder (CR + PR) group showed a better five
year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but
the difference was not significant.
PMID- 9643002
TI - [The mechanism of positive scintigraphy with 99mTc-pertechnetate in
adenolymphomas of the parotid grand].
AB - In order to clarify the mechanism of positive scintigraphy with Tc pertechnetate
in adenolymphomas of the parotid gland, 10 cases of adenolymphoma were studied
morphologically and from a functional view point. Salivary tissue obtained from
normal parotid glands were also investigated for comparison with the tumor. In
morphological studies, rapid tissue fixation by microwave irradiation produced
very good results for examining mitochondria by high resolution light microscopy.
A number of mitochondria were found both in the epithelial cells of adenolymphoma
and in the striated duct cells of the parotid gland. In functional studies, the
one-step method of enzymatic histochemistry was used for detecting Na-K ATPase.
Na-K ATPase was found on the baso-lateral side of the epithelial cells of
adenolymphoma and the striated duct cells of the parotid gland, and this activity
of Na-K ATPase may enhance the accumulation of Tc pertechnetate in these cells.
These observations may provide evidence for the bi-cellular theory which
indicates that adenolymphoma originated from immature intercalated duct reserve
cells.
PMID- 9643004
TI - [The latest design method of the dwellings for the elderly persons].
PMID- 9643003
TI - [Calretinin immunoreactivity in olfactory bulb and mucosa in mice].
AB - The vertebrate olfactory system is capable of recognizing and discriminating
thousands of different odorant molecules. In vitro biochemical studies have shown
that some odorants elicit an increase in the intercellular second messenger
cyclic AMP, whereas other odorants cause an increase in the second messenger
inositol triphosphate (IP3). If IP3 plays an important role in the signal
transduction, calcium-binding protein will be needed. We investigated the
expression of calretinin, which belongs to the E-F hand family, in the neonatal
and adult olfactory mucosa and olfactory bulb. Mice were sacrificed on postnatal
day 1 (P1), day 3 (P3), day 10 (P10) and 12 weeks as adults. The olfactory mucosa
of the nasal septum and the olfactory bulb were stained with anti-calretinin
antibody at a 1:1000 dilution for 48 hours. The results were as follows. 1)
Olfactory mucosa: In the P1 mouse, the olfactory nerves running in the submucosal
layer and olfactory cells in the epithelium were positive. In the epithelium,
immunopositive spots were seen exclusively in the upper half of the epithelium.
In the P3, P10 and adult mice, these spots were seen throughout the olfactory
cell layer. However, the basal cell layer and supporting cells were negative. 2)
Olfactory bulb: In all stages, the olfactory nerve layer and the glomerular layer
were strongly stained. In the external plexiform layer, many cells were positive.
Their shape was bipolar and the size of the cell body was thought to be about 20
microns. They were thought to be tufted cells. However, there is a possibility
that these cells are short axon cells in the external plexiform layer. In the
granule layer, some granule cells were positive. In the P1 mouse, the
immunopositive spots were exclusively seen in the upper half of the epithelium.
In contrast, in the P3 mouse, these spots were seen throughout the olfactory cell
layer. Judging from our results, it is suspected that the important change in
neurogenesis of olfactory cells occurred between P1 and P3. In the olfactory
bulb, from P1 to adult mice, calretinin was positive in the olfactory nerve
layer, the glomerulus and periglomerular cells. In contrast, mitral cells were
negative. Most reports state that calcium binding protein appears in
periglomerular cells. However, in the external plexiform layer, many cells were
positive. As their shape was bipolar and the cell body was a little larger than
the periglomerular cells, these cells were thought to be tufted cells.
PMID- 9643005
TI - [Biological function of AGE].
PMID- 9643006
TI - [Molecular mechanism of neuronal cell death in Alzheimer's disease].
PMID- 9643007
TI - [Effect of inflammatory cytokines and oxidized low density lipoprotein on
vascular endothelial growth factor expression in macrophage].
AB - Vascular endothelial growth factor (VEGF), also known as vascular permeability
factor, is a specific mitogen for vascular endothelial cells and causes
neovascularization and capillary hyperpermeability. We previously found large
amounts of VEGF peptide in areas with many macrophage-derived foam cells adjacent
to the lipid core of human atherosclerotic plaques and in basal regions of plaque
consisting predominantly of smooth muscle cells. In the present study, we
examined the role of inflammatory cytokines and oxidative modified low density
lipoprotein (OX-LDL) in the expression of macrophage VEGF. Interleukin 1 beta and
tumor necrosis factor alpha upregulated the expression of VEGF mRNA in a
macrophage cell line (RAW264). In addition, OX-LDL also upregulated the
expression of VEGF mRNA in these cells in a time-dependent and a dose-dependent
dependent manner, and there was an increase in the levels of VEGF protein in the
conditioned medium. These results suggest that VEGF expression may be upregulated
in atherosclerotic lesions and that VEGF may play a role in the development of
atherosclerosis.
PMID- 9643008
TI - [Characterization of amyloid beta protein species in the plasma, cerebrospinal
fluid and brains of patients with Alzheimer's disease].
AB - Extracellular deposition of amyloid beta protein (A beta) as senile plaques and
cerebral amyloid angiopathy (CAA) is one of the essential pathological
characteristics of Alzheimer's disease (AD). Several A beta species with
different carboxyl termini, including A beta 42 (43) and A beta 40 ending at
residue 42 (43) and 40, respectively, have been identified in CAA and in senile
plaque cores. Because A beta 42 (43), the major component of diffuse plaque which
is the earliest pathological change in AD brains, forms insoluble amyloid fibrils
more rapidly than does A beta 40, it has been hypothesized that A beta 42 (43)
plays a role in amyloid seeding and A beta 40, in the elongation of amyloid
fibrils on a seed of A beta 42 (43). We used enzyme-linked immunosorbent assay
(ELISA) with site-specific monoclonal antibodies to differentiate A beta 42 (43)
from A beta 40. First, we measured the amounts of different A beta species in
plasma from patients with sporadic probable AD, age-matched patients with
neurologic diseases but without dementia, and age-matched normal controls.
Concentrations of A beta 1-40 and A beta 1-42 (43) in plasma did not differ
significantly among the three groups. Second, CSF levels of A beta species (CSF-A
beta) with different carboxy termini, i.e., A beta X-40 and A beta X-42 (43) as
well as A beta 1-40 and A beta 1-42 (43), were measured in patients with AD and
in age-matched controls without dementia using ELISA. Levels of both CSF-A beta X
42 (43) and A beta 1-42 (43) were significantly lower in the patients with AD
that in the controls, but neither the levels of CSF-A beta X-40 nor those of CSF
A beta 1-40 differed between the two groups, which suggest that increased
adsorption of A beta 42 (43) to A beta deposition in AD brains, decreased
secretion of A beta 42 (43) in CSF, or increased clearance of A beta 42 (43) from
CSF might explain the low levels of A beta 42 (43) in the CSF of patients with
AD. Third, we measured the concentrations of various A beta species post-mortem
in the cerebral cortex of patients with PS-1 mutations and beta amyloid precursor
protein (APP) 717 mutation linked to familial AD or Down syndrome. The results
indicate that one effect of PS-1 mutations, APP717 mutation and Down syndrome is
to cause dramatic and accelerated accumulation of A beta 42 (43) in the brain as
compared with sporadic AD. In particular, the increases in A beta 1-42 (43)
showed a crude inverse correlation with the age of onset in each subtype of AD.
Thus, quantitative studies differentiating A beta 42 (43) from A beta 40 have
established the fundamental importance of A beta 42 (43) in AD.
PMID- 9643009
TI - [DNA analysis for prevention and treatment of osteoporosis].
PMID- 9643010
TI - [A new approach to pneumonia in the elderly: pathophysiology and therapy].
AB - Pneumonia is a major cause of death in the elderly. Swallowing disorders caused
by cerebrovascular diseases can cause frequent aspiration during sleep, which can
result in pneumonia. Patients with aspiration pneumonia may have abnormalities in
systems involving dopamine-substance P in the central and peripheral nervous
system. Activation of these systems may benefit elderly people with swallowing
disorders.
PMID- 9643011
TI - [Mutation analysis of S182 (presenilin-I) in patients with familial Alzheimer's
disease and its biological function].
AB - We report the clinical and neuropathologic phenotypes associated with two
missence mutations in the presenilin I (PS I) gene in Japanese patients with
early-onset familial Alzheimer's disease. The AM/JPN1 family showed a missense
mutation (C-->T) which is predicted to cause an Alanine to Valine missense
substitution at codon 260 (A260V). The disease in the members of this family had
a mean age-of-onset of 40.3 years old (the range of disease is 8-19 years).
Neuropathologic studies of two members of AM/JPN1 pedigree showed wide-spread
senile plaques, neurofibrillary tangles, and neuronal loss, as well abundant
perivascular subpial amyloid deposits in the Virchow-Robin spaces and Pick-like
intraneuronal inclusions in the dentate gyrus. In the second pedigree
transmitting a C-->T nucleotide substitution leading to the missense mutation of
Alanine to Valine at codon 285 (A285V), the disease had a later age of onset
(mean, 51 years) but a more rapid course. Comparison of the disease phenotypes
associated with other missense mutations in exon 9 of PSI reveals no obvious
clinical or pathological phenotype that uniquely distinguishes Alzheimer's
disease associated with PS I mutations from other early-onset familial
Alzheimer's disease. This implies that the variable phenotypes of familial
Alzheimer's, disease might be attributable to factors other than the PS gene.
PMID- 9643012
TI - [Positional cloning of susceptibility genes for non-insulin-dependent diabetes
mellitus].
AB - Although studies of families and twin studies have demonstrated that non-insulin
dependent diabetes mellitus (NIDDM) has a strong genetic component, the genes
responsible for the common forms of NIDDM are largely unknown, due to the complex
and heterogeneous nature of the disease. To study the genetics of NIDDM, we used
an inbred animal model of NIDDM, the NSY mouse, in which NIDDM spontaneously
develops in an age-dependent manner. The inheritance pattern of glucose
tolerance, fasting insulin levels, insulin response to glucose, body mass index,
and epididymal fat pad weight in F 1 hybrids of NSY with control C3H/He mice
suggested the different modes of inheritance in these phenotypes. Multipoint
linkage analysis of glucose tolerance in F2 mice with microsatellite markers
throughout the genome mapped at least three loci on different chromosomes.
Positional cloning of susceptibility genes for NIDDM in NSY mice may increase our
understanding of the genetics and etiology of human NIDDM and may lead to more
effective methods for prevention and intervention.
PMID- 9643013
TI - [Okinawa Longevity Study. Molecular genetic analysis of HLA genes in the very
old].
AB - We analyzed HLA class II genes of Okinawan centenarians using the polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to
identify primary genetic factors in the major histo-compatibility complex (MHC)
region associated with human longevity. Gene frequencies of centenarians were
compared with those of normal adults of the same ethnicity who were selected in
the same vicinity as the centenarians. The following differences were identified
in the HLA-DQB1 and DQA1 genes: the frequencies of DQB1*0503, DQA1*0101 (04) and
DQA1*05 were increased in the centenarians, whereas those of DQA1*0102, DQA1*0103
and DQB1*0604 were decreased. Similarly, for the DRB1 gene, the frequencies of
DRB1*0101, DRB1*1201 and DRB1*1401 were increased in the centenarians, whereas
those of DRB1*0403 and DRB1*1302 were decreased. These data suggest that several
alleles of the HLA-DRB1 and/or HLA-DQ genes are involved in human longevity.
PMID- 9643014
TI - [Effect of warm bathing on blood pressure in bedridden patients].
AB - The effects of warm bathing on short-term and circadian rhythms for blood
pressure (BP), pulse rate (PR), and endocrine function were studied in 10 bed
ridden patients (5 men and 5 women; age 78.9 +/- 10.5 years old) hospitalized in
Nomura Municipal Hospital. The results indicated a transient elevation of BP with
bathing and its rapid fall after bathing. Compared with the days when patients
did not take bath, systolic BP was significantly lower for 12 to 16 hours (p <
0.005) after bathing and diastolic BP was also significantly lower during 8 to 12
hours (p < 0.01), 12 to 16 hours (p < 0.001) and 20 to 24 hours (p < 0.001). The
PR was significantly higher from 0 to 4 hours after bathing (p < 0.01), but
became significantly lower during 8 to 12 hours (p < 0.001) and 12 to 16 hours (p
< 0.001). Plasma renin activity increased significantly after bathing (p < 0.05).
Thus, the effects of bathing in lowering BP of bedridden patients in stable
condition may continue for several hours after bathing.
PMID- 9643015
TI - [An animal model of aspiration and aspiration pneumonia using lacZ gene
expression in lungs by adenoviral vectors].
AB - To examine the relationship between disturbed upper airway reflexes and
aspiration pneumonia, we administered a total volume of 20 microliters of Ad-CMV
lacZ (Ad vector) or 20 microliters of phosphate buffer solution (PBS) intranasal
to C57 black mice. In nostrils, the lacZ gene expression was investigated in each
mouse with or without anesthesia. Under anesthesia, the lacZ gene expression was
detected by Xgal staining in the lungs of every mouse given the Ad vector.
However, no gene expression was measured in the lungs of those given the Ad
vector without anesthesia. In mice treated with PBS, there was no lacZ gene
expression in the nostrils, trachea, or lungs, irrespective of anesthesia. These
results suggest that unconsciousness or disturbed upper airway reflexes caused by
anesthesia caused aspiration, resulting in an intranasal bolus that can reached
the lower airways. This process can be analyzed in mice tracted with adenovirus
vectors carrying the E. coli LacZ gene. Mice given Ad-CMV-lacZ transnasally can
be used to study aspiration pneumonia in relation to unconsciousness.
PMID- 9643016
TI - [Relationship between cognitive function and discharge place among stroke
patients after rehabilitation].
AB - One hundred and ninety-nine elderly stroke patients, who received rehabilitation
treatment, were examined, to clarify the relationship between cognitive function
and discharge place. The patients who moved to long-term care facilities showed
more severe disabilities of basic activities of daily living (ADL), more frequent
incontinence, and lower functional impairments (Brunnstrom stage), compared with
those discharged to their home. Multivariate regression analysis was done with
discharge place as the dependent variable. Independent variables were age, sex,
kind of stroke, rehabilitation period, level of ADL and IQ on Kohs test, or
performance IQ on the Wechsler Adult Intelligence Scale. Older age, higher levels
of ADLs, and higher scores on Kohs test IQ or Wechsler Adult Intelligence Scale
Performance IQ were all significantly linked with home discharge. These results
suggest that non-verbal cognitive dysfunction may affect discharge place in
elderly stroke patients after rehabilitation therapy.
PMID- 9643017
TI - [Relationships of psychological, physical, blood measurements to EEG findings
among the aged in nursing home].
PMID- 9643018
TI - [Sorsby's fundus dystrophy. A genetically homogeneous disease].
AB - BACKGROUND: The recent identification of the tissue inhibitor of
metalloproteinases-3 (TIMP3) as the gene underlying SFD pathology has made it
possible to address the question of genetic heterogeneity in this disorder. In
addition, it now has become feasible to clarify whether SFD is directly involved
in other maculopathies and, in particular, may represent a genetic model for age
related macular degeneration. PATIENTS: Genetic analysis were performed in five
unrelated and 18 related British SFD pedigrees as well as in 143 patients
affected with age-related macular degeneration, 28 patients with adult
vitelliform macular dystrophy, 21 patients with central areolar choroidal
dystrophy and 25 individuals with other forms of macular dystrophies. RESULTS:
Molecular genetic analyses confirmed the autosomal dominant mode of inheritance
in SFD. In all five unrelated SFD pedigrees individual TIMP3 mutations were
identified introducing an additional cysteine residue into the C-terminal region
of the mature protein. Affected individuals from 18 SFD families residing in
Great Britain, Canada, Oregon and South Africa were found to carry a common
ancestral Ser181Cys mutation. The clinical variability of this Ser181Cys mutation
was reevaluated. A mutational screen in 217 patients with various maculopathies
revealed no disease-causing mutations in the TIMP3 gene. CONCLUSION: So far,
TIMP3 mutations have exclusively been associated with SFD. Therefore, this
disorder appears to be genetically homogeneous with complete penetrance but
variable expressivity.
PMID- 9643019
TI - [Ultrastructural localization of lipid peroxides in the eye. Presentation of a
new method].
AB - Lipid peroxidation is considered a prominent feature of age-related retinal
degeneration. It is known that lipid peroxides can oxidize benzidine. This
property was used to localize lipid peroxides ultrastructurally in the retina.
METHODS: (1) Lipid peroxides were formed by incubation of linoleic acid with
lipoxygenase from soybean, separated by thin layer chromatography and incubated
with tetramethylbenzidine. (2) Lipid peroxides were formed by incubation of
porcine retinae with soybean lipoxygenase in an oxygensaturated atmosphere. For
ultrastructural localization, isolated retinae with and without enzymatically
synthesized lipid peroxides were fixed with 2% glutaraldehyde, incubated with 0.5
mg/ml tetramethylbenzidine and embedded for electron microscopy. (3) Eye cups
from Syrian golden hamsters were treated in the same way except for incubation
with lipoxygenase. The hamsters were kept under constant illumination (1000 lux)
for 12 h to enhance lipid peroxidation. RESULTS: (1) Tetramethylbenzidine was
oxidized by linoleic acid peroxides. (2) In the isolated retinae of pigs lipid
peroxides became visible as electron-dense structures in the rod outer segments
(ROS) after treatment with lipoxygenase and were lacking in the other parts of
the retina. Without treatment with lipoxygenase lipid peroxides were only
infrequently seen in ROS. (3) In the eyes of light-exposed hamsters, electron
dense reaction products of lipid peroxides were particularly prominent between
the basal infoldings of the RPE and within the apical parts of the ROS.
CONCLUSION: Light or enzymatically induced lipid peroxides can be localized
ultrastructurally due to their ability to react with tetramethylbenzidine and
osmium in the absence of H2O2 to an electron-dense reaction product. Lipid
peroxides seem to be removed from the RPE via Bruch's membrane and blood vessels.
Disturbance of this pathway may enhance lipofuscin or drusen formation.
PMID- 9643020
TI - [Choroid neovascularization in age-related macular degeneration. Correlation of
histological and fluorescence angiography findings].
AB - BACKGROUND: Recent studies have raised confusion about the fluorescein
angiographical and histopathological correlation of CNV. MATERIAL AND METHODS:
The preoperative fluorescein angiograms of four patients with subfoveal CNV due
to ARMD extracted by pars plana vitrectomy were classified as wellor ill-defined
CNV and were correlated to the histopathologically (in serial sections) verrified
CNV-location (subneuroretinal (= type II according to Gass) versus sub-RPE (type
I according to Gass)). RESULTS: The locations of all four CNV could be classified
by histopathological landmarks as there were RPE, BLD/drusen, and inner Bruchs
membrane. Angiographically welldefined membranes were type II membranes according
to Gass, whereas the ill-defined membrane represented type I. The CNV with well-
and ill-defined borders consisted of type II and type I parts according to Gass.
CONCLUSION: We find subneuroretinal locations of the well-defined CNV examined
(type II membranes according to Gass). Correspondingly, ill-defined CNV or ill
defined parts of a CNV seem to be beneath the RPE (type I). The correlation of
fluorescein angiography and histopathology should be studied in greater numbers
of well- and ill-defined CNV.
PMID- 9643021
TI - [Adhesion of liquid perfluorocarbon to various intraocular lens materials. A
light microscopy study].
AB - INTRODUCTION: Perfluorocarbone liquids (PFCL) enable explantation of intraocular
lenses (IOL) dislocated into the vitreous. Because of their relatively high
specific weight, the IOL can be floated off the retina and repositioned in the
anterior segment. If the IOL surface is affected by contact with PFCL is still
unknown. We were interested in the extent of PFCL contact with different IOL
materials, having in mind a repositioning of a dislocated IOL into the posterior
chamber. We investigated the adherence of PFCL to different IOL surfaces.
MATERIALS AND METHODS: The following IOL materials were tested: Group I:
acrylate/methacrylate polymers: (a) PMMA, compression molding; (b) PMMA,
compression molding, heparin-surface modified; (c) poly-hydroxyethylmethacrylate
(polyHEMA); (d) phenylethylacrylate, phenylethylmethacrylate; (e)
methylmethacrylate, HEMA; (f) methylmethacrylate, hydroxyethylmethacrylate,
ethylene glycol dimethacrylate; (g) hydroxyhexylmethacrylate, HEMA. Group II:
silicone elastomers: (a) polydimethylsiloxane; (b) polydimethyldiphenylsiloxane.
A total of 17 types of standard quality IOLs were obtained from several
manufacturers. Each IOL was immersed in PFCL for 3 h. Then each IOL was rinsed
with 2 ml balanced salt solution (BSS) and investigated by light microscopy with
regard to the extent of PFCL adhesion. RESULTS: After rinsing with BSS, no PFCL
was detectable on any IOL surface. Possible PFCL invasion into an open optic
haptic junction in three-piece IOLs could not be excluded using this method. All
IOLs demonstrated optic and haptic surfaces without alterations. The IOL surfaces
were comparable to those of new IOLs. CONCLUSIONS: With respect to PFCL-IOL
interaction, all IOLs seem to be inert. After luxation of the IOL into the
vitreous and IOL elevation by using PFCL, repositioning of the dislocated IOL
seems to be possible under special conditions (adequate total diameter, IOL
without damage, no open haptic junction in the optic). After rinsing the
explanted IOL with BSS prior to reimplantation, the risk of damaging the eye by
PFCL remnants on the IOL appears neglibile.
PMID- 9643022
TI - [Intraocular lens implantation in childhood. Functional results and
complications].
AB - IOL implantation in childhood is still controversial. INTENTION: The purpose of
this retrospective study was to evaluate functional results and complications in
children after IOL implantation. METHODS AND RESULTS: Posterior chamber IOLs were
implanted in 52 eyes of 45 children. Cataract extraction was necessary because of
traumatic, congenital/developmental and secondary lens opacities. Nine IOLs were
implanted in children between the ages of 1.9 and 4 years, 17 IOLs from 4 to 8
years and 26 IOLs in patients 8 to 14.3 years old. In 38 of the 52 eyes (73%)
vision improved after the surgery. Fifty-four percent had an acuity of at least
0.5. The functional results of children more than 8 years old were superior to
those of younger patients. Children with traumatic cataracts had better visual
acuities than those with other types of cataract. Except for secondary capsular
opacities (75%) that could not be prevented by performing a primary posterior
capsulotomy or capsulectomy and iris capture (31%), postoperative complications
were rare. CONCLUSION: Favorable functional results can be achieved by IOL
implantation in children with cataracts. Many patients require secondary surgical
procedures because of capsular opacities and iris capture.
PMID- 9643023
TI - [Corneal topography of the partner eye in unilateral keratoconus].
AB - PURPOSE: To study the incidence and shape of subclinical keratoconus with corneal
topography in the fellow eye in the case of clinically, slit-lamp
biomicroscopically and topographically diagnosed unilateral disease. METHODS:
Eighty patients with keratoconus were fitted with contact lenses. Twelve of them
revealed clinical features of unilateral disease. In these patients we performed
a computed topographic analysis in the clinically normal fellow eye. We measured
quantitative parameters (central corneal power, I-S value) and qualitative
parameters (localization and shape of corneal steepening). RESULTS: In all 12
patients we found in the fellow eye no slit-lamp evidence for keratoconus. Nine
patients were emmetropic in the fellow eye, three patients myopic between -1.5
and -4.0 D. The myopia in these patients was corrected with contact lenses and
the investigation was performed 5 days after discontinuance of contact lenses.
The corneal topography showed the typical keratoconus pattern in 11 patients with
a steepening of the inferior cornea and in 1 case a superior steepening of the
cornea; range of I-S values -1.0 to +5.0 D. All patients revealed a configuration
of oval type cone keratoconus in the corneal topography. CONCLUSION: Keratoconus
occurs with a high degree of bilaterality, but with onset of the disease at
different times in the two eyes. Corneal topography seems to be a sufficient
method to detect early keratoconus.
PMID- 9643024
TI - [Combined myopia-astigmatism correction. A comparison with pure myopia
correction].
AB - BACKGROUND: Myopic PRK up to 6 D is an approved and safe procedure. The efficacy
and safety of combined treatment of myopia and astigmatism in compound myopic
astigmatism (PARK) have not yet been demonstrated. PATIENTS AND METHODS: In a
prospective study in 342 eyes the results of myopic PRK were compared to those of
correction of compound myopic astigmatism (PARK). RESULTS: Regarding spherical
refraction achieved there was no significant difference between groups. Best
corrected visual acuity only improved in the group with high astigmatism; this
group also showed the least number of Central Islands. Permanent haze and steroid
induced glaucoma or cataract were not observed after treatment up to 6 D. Average
astigmatism of 2.24 D was be reduced to 0.53 D 1 year post-operatively.
CONCLUSIONS: Correction of astigmatism resulted in undercorrection of
approximately 30%. Our experience with the keracor shows PRK up to 6 D with or
without additional correction of astigmatism (PARK) to be comparatively safe in
terms of regression and complications and equally accurate in reaching spherical
target refraction.
PMID- 9643025
TI - [Primary orbital implant dislocation. A retrospective study].
AB - BACKGROUND: To compensate the orbital volume deficit after enucleation orbital
implants are used. METHOD: Between 1986 and 1996, 449 enucleations were
performed. One hundred and fifty-five orbital implants were used: 96
hydroxylapatite-ceramic-silicon (HAK-silicon), 29 hydroxylapatite-ceramic (HAK),
26 Kiel bone chips, 3 Walser and 1 Bangerter implant. RESULTS: Ten orbital
implants (6.45%) had to be explanted. Seven of the 96 HAK-silicon implants were
explanted: four could be changed, two of them with a smaller and two with a same
diameter. We observed a complication rate of 7.29% and a rate of total loss of
3.13%. One luxated HAK-implant could be refixated (3.45%), and one implant
(3.85%) of the Kiel bone chip implants was explanted. CONCLUSION: Using different
types of orbital implants after enucleation, we observed a complication rate of
7%. However, to avoid the post-enucleation-syndrome and to achieve better
motility of the prosthesis, orbital implants should be used.
PMID- 9643026
TI - [Epidemiology of severe eye injuries. United States Eye Injury Registry (USEIR)
and Hungarian Eye Injury Registry (HEIR)].
AB - BACKGROUND: Both in industrialized and in developing nations, the devastating
impact of ocular trauma on society is increasingly recognized. Lacking
standardized surveillance systems, however, comparable epidemiological
information has not been available previously. METHODS: For several years, the
United States Eye Injury Registry (USEIR) and the Hungarian Eye Injury Registry
(HEIR) have been collecting data on all types of serious ocular trauma, based on
identical operating criteria and using standardized reporting forms. We performed
a retrospective analysis comparing the two datasets, containing over 8,400
injuries from the U.S. and over 1,200 injuries from Hungary. RESULTS: Sixty
percent of patients in the U.S. and 52% of patients in Hungary were less than 30
years of age, with an at least 80% male preponderance in both registries. The
home was the most frequent place of injury in both countries (USEIR: 41%, HEIR:
35%); industrial premises represented no more than 14%. Guns were responsible for
12% of cases in the USEIR (HEIR, 1%). Champagne corks were identified as a unique
and relatively common source of eye injury in Hungary (1.4%, as opposed to 0.07%
in the U.S.). In the USEIR, 16% of injuries were caused by assault (HEIR, 24%;
chi-square value = 36.7, p < 0.0000001). The enucleation rate was 12% in the U.S.
and 1% in Hungary. CONCLUSIONS: The different findings in the two countries
identify certain areas for the implementation of preventive measures (supplying
champagne bottles with warning labels and a coordinated fight against violence in
Hungary, stricter fireworks legislation in the U.S., public awareness for home
injuries in both countries, etc.). Based on the encouraging results from this
study, we plan to continue our efforts using modified reporting forms and an
upgraded software. We invite additional countries to adopt the USEIR model.
PMID- 9643027
TI - [Bilateral simultaneous acute amaurosis in neuritis nervi optici. Initial
manifestation of encephalomyelitis disseminata].
AB - BACKGROUND: Bilateral simultaneous acute amaurosis as a primary manifestation of
demyelinating disease is extremely rare. PATIENT: The clinical course of a 24
year-old patient who initially presented with a bilateral complete loss of vision
is demonstrated. Morphologically both optic discs appeared slightly blurred and
prominent. Otherwise there were no anterior and posterior segment abnormalities.
Examination of the cerebrospinal fluid revealed an increased number of cells and
protein without oligoclonal bands. On MRI multiple white matter lesions were
visible. Laboratory tests showed no specific abnormalities, especially with
respect to infectious or vasculitic diseases. Under intensive steroid therapy
(initially 1000 mg prednisolone/day), visual acuity recovered almost completely.
Nine months after onset of the disease visual acuity was 1.0 in both eyes.
CONCLUSIONS: Even in patients with a fulminant onset of the disease almost
complete visual recovery is possible. Differential diagnosis should rule out
vasculitic autoimmune optic neuritis, infections, tumors, processes of the
paranasal sinuses, toxic, and hereditary causes.
PMID- 9643028
TI - [Bilateral retinal tumors in a child. Tuberous sclerosis with retinal
astrocytomas].
PMID- 9643029
TI - [Development of the filtering bleb after trabeculectomy. Classification,
histopathology, wound healing process].
PMID- 9643030
TI - [Orthodontics in the 21st century: a multidisciplinary].
PMID- 9643031
TI - [An interview with Dr. Vincent Kokich. Interview by Sophie Rozencweig].
PMID- 9643032
TI - [An interview with Pr. Annika Isberg. Interview by Georges Rozencweig].
PMID- 9643033
TI - [An interview with Pr. Sandro Palla.. Interview by Gerard Lebre].
PMID- 9643034
TI - [Occluso-orthodontic course].
PMID- 9643035
TI - [Articular surgery in the treatment of temporomandibular dysfunction].
AB - The temporomandibular joint surgery is developing towards less invasive
procedures. Open surgery provides a lot of complications. Arthroscopy is now
almost the only common used procedure, especially lysis and lavage.
Arthrocentesis provides good results too. However, careful preoperative and
appropriate nonsurgical care are essential. Only 5 and 7% of the patients who are
treated for TMJ disorders and dentofacial deformity, TMJ surgery precedes
surgical/orthodontic treatment.
PMID- 9643036
TI - [Occlusion and dysfunction: the paradox of dentofacial orthopedics].
PMID- 9643037
TI - [MRI study of temporomandibular joint disk behavior in chilren with
hyperpropulsion appliances].
AB - Orthodontic and orthopaedic effects of hyperpropulsors have been studied,
evaluating the possible adaptation of the temporo mandibular joint. Before the
event of MR imaging, the positional modification of the disc could not be seen.
The study has been carried out on 15 subjects, skeletal Class II, with a mean age
of 11.6 years (SD = 1 year). A bilateral MR investigation has been done before
and after the wear of an activator (Herbst or Monobloc with Head Gear). All
patients underwent bilateral imaging in sagittal and modified coronal planes in
closed and opened mouth. The qualitative analysis of the temporo-mandibular
joints reveals the appearing of internal derangements, often asymptomatic, in one
case out of five; the disc being anteriorly displaced on an average of 8.3
degrees (p = 0.023). These results need to be confirmed on larger samples but may
modified functional approach of orthopaedic treatments in order to take into
account the TMJ change.
PMID- 9643038
TI - [The development of craniomandibular disorders after bilateral sagittal
osteotomy].
AB - The aim of this study is to know the repercussions of modified sagittal ramus
split osteotomy of the mandible on the anamnesic symptoms of cranio-mandibular
disorders in 89 patients. The sample was divided into different groups according
to the surgery type: mandibular advancement or mandibular retrusion with or
without maxillary surgery. The anamnesic approach allows to evaluate the felt
symptoms. All had a surgery by the same surgeon and with the same technique:
mandibular sagittal bilateral surgery according to the modificated Obwegeser
osteotomy. The statistical analysis shows some differences between groups.
PMID- 9643039
TI - [An interview with Dr. Robert L. Boyd. Interview by Christian Demange].
PMID- 9643040
TI - [An interview with Dr. Henry Salama. Interview by Gerard Lebre].
PMID- 9643041
TI - [Clinical attitudes toward periodontal risk].
AB - After having defined the conditions that will start the loss of attached gingiva,
the author develops the characteristic of the patient at periodontal risk. He
then explains the value of the interview as well as that of the clinical and
microbiological exams, insisting on the therapeutic outcome of those exams, and
on the effect of the flora.
PMID- 9643042
TI - [Conditions of the successful outcome of mucogingival surgery during orthodontic
treatment].
AB - For the last twenty years the mucogingival surgical technics, particularly
displaced flaps, have brought gingival tissue when it is missing improving the
periodontic outcome of orthodontic treatment. The displaced flaps are indicated
where is a deficient attached gingiva or for uncovering retained cuspids. This
state of the art is done both for the surgical and orthodontic care that are
necessary as well as for the possible problems and complications after surgery.
PMID- 9643043
TI - [The importance of periodontal evaluation in orthodontics].
AB - The orthodontist is in fact a periodontal-therapist since his aim is to move the
teeth with and through the periodontal tissues. It is most important for the
orthodontist to be able to determine at the initial clinical examination what are
the various periodontal risk factors. When the pathology is obvious with
inflammation, periodontal pockets, gingival hyperplasia, edema of the papillae,
gingival recessions, the need for periodontal treatment is manifest. But many
times, the periodontal evaluation is complicated by the presence of slight
variations of the quality of the marginal tissue that represent a risk of
developing periodontal defects during the orthodontic treatment. The aim of this
presentation is to put forward the importance of the periodontal evaluation
during the initial examination of the patient so that, if necessary, an adequate
periodontal therapy can be initiated to stabilize the periodontal tissues and
thus improves the esthetical outcome.
PMID- 9643044
TI - [Pre-orthognathic surgery in orthodontics: towards justification].
AB - This work presents long term results of rhinopharyngeal desobstructions on nine
years old patients. By using several techniques such as: tonsillectomies,
adenoidectomy, adenoidotonsillectomies, luxation of inferior turbinates, partial
turbinectomies or bilateral turbinectomies under endoscopic guidance, and then,
following carefully the oral and nasal peak flows for a period as long as one or
two years, it becomes obvious that the most efficient desobstruction procedure is
accomplished through a combination of E.N.T. rhinopharyngeal procedures, i.e.
adenoidotonsillectomies and inferior turbinectomies under endoscopic guidance.
This global E.N.T. procedure is known as "Chimney Sweep". The author demonstrates
that tongue behavior is severely affected by rhinopharyngeal obstruction and by
the consecutive dysfunction of the upper airway ventilation pattern. Large
tongues and normal tongues pushed forward due to enlarged tonsils or adenoids are
also affected by their necessary participation to oral ventilation (mouth
breathers). Addition of a selective lingual glossoplasty or a partial glossectomy
is sometimes necessary to put the morphogenic function in a proper order during
growth and development. All of the above is part of a new pre-orthognathic
concept, that helps control growth and development and helps manage orthodontic
or orthognathic treatments.
PMID- 9643045
TI - [The role fo function in the growth of form].
AB - The cranio-facial shape is the outcome of growth, unequally influenced by
heredity and environment. Even if limited, the influence of function is certain,
and results essentially from neuromuscular behavior. This relationship imposes
the taking into account and correction of any functional abnormality by training,
during the correction of malocclusions.
PMID- 9643046
TI - [Arguments apropos of surgery of orofacial functions].
PMID- 9643047
TI - [An interview with the maxillofacial surgeon G. William Arnett. Interview by
Colette Orival-Demange].
PMID- 9643048
TI - [An interview with Dr. W.H. Bell and Dr. C. Mannai. Interview by Colette Orival
Demange].
PMID- 9643049
TI - [Regarding orthognathic surgery].
AB - The author scrutinises the evolution of orthognathic surgery for the last twenty
years through the different parameters that participate to its origin; esthetic
motivation, orthodontico-surgical collaboration, the limitation of widely used
technics, a simple surgical solution, the spreading of rigid fixation, the
interest of primary or secondary genioplasty, the consideration of ethnic
differences,the usefulness of a maxillo-facial chain, the possible retreatment of
failures and consideration for the stability of results.
PMID- 9643050
TI - Mismatch negativity in dichotic listening: evidence for interhemispheric
differences and multiple generators.
AB - The characteristics of mismatch negativity (MMN) elicited by dichotic stimulation
were examined using frequency-deviant stimuli presented to the right, to the
left, or to both sides. The experiment was run twice, once using earphones and
once using loudspeakers in free field. With both modes of stimulation, deviants
presented in the left, right, or both ears, or tones that were switched between
ears, elicited comparable MMNs, with a peak latency of about 180 ms. With
earphones, the amplitude of the MMN was bigger at the frontal-lateral right
hemisphere sites than at the homologous left-hemisphere sites for all deviance
conditions. Scalp current density analysis revealed that deviance in the right
side elicited bilaterally equivalent frontal current sinks and a trend towards
stronger contralateral current sources at the mastoid sites. In contrast, left
side deviance elicited frontal sinks and temporal current sources stronger over
the right hemiscalp. These results are compatible with the multiple-generator
model of MMN. The attention-related role of the MMN is discussed, suggesting
comparable attention mechanisms for vision and audition.
PMID- 9643051
TI - On the automaticity of ipsilateral response activation in the Simon effect.
AB - The effects on performance of unattended stimulus-response spatial relationships
in choice reaction time tasks (i.e., the Simon effect) have been attributed to
automatic activation of the response ipsilateral to stimulus location. We tested
this assumption using the lateralized readiness potential (LRP). The response key
labels changed randomly from trial to trial and were presented either 400 ms
before (immediate-reaction trials) or 400 ms after (delayed-reaction trials)
stimulus. The critical test for the automatic activation hypothesis was on
delayed-reaction trials, in which LRP deflections were expected in the interval
between stimulus and response-key labels. Contrary to this prediction, there were
no LRP signs of response activation within that interval.
PMID- 9643052
TI - Frontal brain asymmetry and affective style: a conceptual replication.
AB - Recent studies have demonstrated that positive and negative affective reactivity
can be predicted by resting electroencephalographic (EEG) asymmetry in frontal
brain regions. These studies used different methods to assess asymmetry and
affectivity. The goal of the present study was a conceptual replication of these
results and to investigate their independence of employed procedures. Resting EEG
of 37 subjects was recorded and affective slides were presented to obtain ratings
of subjects' emotional reactions. Different procedures were applied to the data
to assess the relation between asymmetries and affective reactivity. Depending on
the particular analysis procedure, there were associations between anterior
asymmetry and affectivity in line with the published findings, opponent to those
findings, or no relation between anterior asymmetry and affective reactivity.
PMID- 9643053
TI - Resting frontal electroencephalographic asymmetry in depression: inconsistencies
suggest the need to identify mediating factors.
AB - Two studies of the relationship between depression and resting frontal
electroencephalographic (EEG) activity are reported. Although considerable
research supports the theory of left and right hemispheric specialization for
approach and withdrawal behaviors, only four studies involving clinically
depressed individuals have been published to date. Despite methodological
similarities with published research, no significant differences in frontal
activation emerged between depressed and nondepressed participants with either
college students having high Beck Depression Inventory scores (Study 1) or with
individuals diagnosed with DSM-III-R depression (Study 2). Post hoc analyses in
Study 2 revealed one effect confined to lateral frontal leads during the first 2
min of EEG data; this finding was significant in only one of three reference
montages. Results are discussed in light of methodological considerations and
mediating variables such as temperament and coping styles.
PMID- 9643054
TI - Effect of feedback signal and psychological characteristics on blood pressure
self-manipulation capability.
AB - Blood pressure presentation mode and personality are likely to influence
biofeedback outcome. Thirty-six normotensive subjects were randomly assigned to
visual or auditory continuous systolic feedback. "Distracting speech" and "broad
band noise" were also superimposed and the effect on the biofeedback response was
investigated. Psychological influence was also investigated. Systolic pressure
reduction of 4 +/- 4.3 mmHg (visual, p = .04) and 5 +/- 5.5 mmHg (visual +
auditory, p = .03) were achieved compared with auditory feedback (2 +/- 4.7
mmHg), which was less effective. The addition of noise or speech had no effect on
the systolic response, but speech adversely affected diastolic reduction (p =
.04). Mood (p = .003) was associated with systolic lowering, whereas increased
trait anxiety (p = .06) and expectation (p = .03) had trends for opposite
effects. Increased anger-hostility, state-anxiety, and expectation (p = .06) had
links with systolic raising capability. We conclude that feedback modality and
psychological characteristics have implications for studies investigating blood
pressure manipulation capability.
PMID- 9643055
TI - Automatic change detection: does the auditory system use representations of
individual stimulus features or gestalts?
AB - The effects of global and feature-specific probabilities of auditory stimuli were
manipulated to determine their effects on the mismatch negativity (MMN) of the
human event-related potential. The question of interest was whether the automatic
comparison of stimuli indexed by the MMN was performed on representations of
individual stimulus features or on gestalt representations of their combined
attributes. The design of the study was such that both feature and gestalt
representations could have been available to the comparator mechanism generating
the MMN. The data were consistent with the interpretation that the MMN was
generated following an analysis of stimulus features.
PMID- 9643056
TI - Influence of respiratory activity on the cardiac response pattern to mental
effort.
AB - A group of 32 healthy adult volunteers completed three blocks of a reaction time
task that varied in the degree of controlled processing load. A rest period
preceded each of the task blocks. The task blocks were presented in the order of
either increasing or decreasing cognitive load. For each of the six periods, mean
values and spectral measures of heart rate and respiration variability were
calculated. The spectral measures were obtained for three different frequency
bands. Differences between the cardiac measures of the task and preceding rest
periods were compared with respect to differences in task load and the order of
task presentation. All comparisons were carried out while adjusting for
respiratory variability in the corresponding frequency band. The frequency band
in which task load-related changes in heart rate variability became manifest
appeared to be dependent on the individual's breathing pattern.
PMID- 9643057
TI - Scaling of movement velocity: a measure of neuromotor retardation in individuals
with psychopathology.
AB - The study of motor slowness based on observational methods has limitations.
Whether motor retardation has a psychomotor or neuromotor basis is unclear
because psychiatric and motor symptoms overlap. Observational methods lack the
precision necessary to distinguish cognitive from motor processes. For the
present study, we used an objective measure of neuromotor dysfunction to quantify
the extent to which an individual programs movement velocity in anticipation of
increasing target distance. Persons with Parkinson's disease (PD) or functional
psychosis were studied with a group of healthy comparison subjects. Results
indicated that the slope of the linear function relating velocity to distance was
abnormal in the PD group and in approximately half of the psychosis group.
Analyses revealed the measure to have high specificity and sensitivity. Weak
correlations between velocity scaling and psychopathology support the neuromotor
basis of the measure. We conclude that this measure of velocity scaling is
relatively uninfluenced by cognitive factors that may underlie psychomotor
retardation.
PMID- 9643058
TI - Maternal exposure to influenza in pregnancy and electrodermal activity in
offspring: a further study from Mauritius.
AB - This study examined the effect of mothers' exposure to the 1957 A2/Singapore
influenza virus in the first, second, and third trimesters of pregnancy on the
electrodermal activity of their 15-year-old offspring. The epidemic occurred
during cold months of the year. The results show that maternal viral (and cold)
exposure during all trimesters of pregnancy produced a lower frequency of
nonspecific electrodermal responses and diminished responsivity to 75-db and 90
db tones as compared with the offspring of mothers who were not exposed. However,
there was a critical effect of second trimester exposure as indicated by an
increase in frequency of nonresponses to orienting tones. The findings are
compared with those from an earlier study from Mauritius involving 3-year-old
children in which the effects of exposure to the 1968 A2/Hong Kong virus were
examined and in which the effect of could exposure could be examined separately
because viral exposure occurred during the hot months.
PMID- 9643059
TI - A longitudinal analysis of eye tracking dysfunction and attention in recent-onset
schizophrenia.
AB - The effect of an attentional manipulation on eye tracking dysfunction (ETD) in
the early stages of schizophrenia was examined in 34 recent-onset schizophrenic
patients and 24 demographically matched normal subjects over a 1-year period. An
attentional enhancement manipulation improved eye tracking performance of recent
onset schizophrenic patients more than that of normal subjects. Eye tracking
level also was moderately stable for both groups over the course of 1 year. The
possible role of attentional allocation in ETD highlights the need for further
examination of the interface between attentional and eye tracking measures of
vulnerability to schizophrenia.
PMID- 9643060
TI - Effects of stimulus modality and task condition on blink startle modification and
on electrodermal responses.
AB - Participants in Experiments 1 and 2 performed a discrimination and counting task
to assess the effect of lead stimulus modality on attentional modification of the
acoustic startle reflex. Modality of the discrimination stimuli was changed
across subjects. Electrodermal responses were larger during task-relevant stimuli
than during task-irrelevant stimuli in all conditions. Larger blink magnitude
facilitation was found during auditory and visual task-relevant stimuli, but not
for tactile stimuli. Experiment 3 used acoustic, visual, and tactile conditioned
stimuli (CSs) in differential conditioning with an aversive unconditioned
stimulus (US). Startle magnitude facilitation and electrodermal responses were
larger during a CS that preceded the US than during a CS that was presented alone
regardless of lead stimulus modality. Although not unequivocal, the present data
pose problems for attentional accounts of blink modification that emphasize the
importance of lead stimulus modality.
PMID- 9643061
TI - Physiological response to a minimal social encounter: effects of gender,
ethnicity, and social context.
AB - This study examined physiological response to an encounter with and touch by an
unfamiliar person. Fifty-five African American (23 male, 30 female) and 51
European American (23 male, 28 female) undergraduates participated. A Black or
White interactor entered the room, introduced himself or herself, checked
equipment for 30 s, and then took a pulse for 30 s. Entry of the interactor
resulted in increased corrugator and zygomaticus facial muscle activity (EMG),
increased skin conductance (SC), and heart rate (HR) acceleration. Corrugator EMG
was greater among Black subjects; White subjects responded with more zygomatic
EMG and SC and greater HR acceleration. Women showed a more positive facial
expression than did men. Being touched reduced EMG and HR but resulted in
increased SC. White and Black males showed more HR acceleration when encountering
a Black male interactor.
PMID- 9643062
TI - Testing treatment effects in repeated measures designs: an update for
psychophysiological researchers.
AB - In 1987, Jennings enumerated data analysis procedures that authors must follow
for analyzing effects in repeated measures designs when submitting papers to
Psychophysiology. These prescriptions were intended to counteract the effects of
nonspherical data, a condition know to produce biased tests of significance.
Since this editorial policy was established, additional refinements to the
analysis of these designs have appeared in print in a number of sources that are
not likely to be routinely read by psychophysiological researchers. Accordingly,
this paper includes additional procedures not previously enumerated in the
editorial policy that can be used to analyze repeated measurements. Furthermore,
I indicate how numerical solutions can easily be obtained.
PMID- 9643063
TI - [Women, human rights and health].
PMID- 9643064
TI - [Water fluoridation in the Region of Murcia].
AB - BACKGROUND: The purpose of this study is that of expounding upon the natural
fluoride ion concentrations in the public water supplies of all of the
municipalities in the Region of Murcia in 1991, in addition to the trend in said
concentrations throughout the 1992-1996 period, this being a time during which
fluoride was added to the water supply as a public health measure. METHODS: The
methods employed for the findings were those of potentiometer-based gauging by
means of standard addition and direct findings using a potentiometer equipped
with an ion-selective electrode. RESULTS: The findings indicate that major
fluctuations have taken place in the amounts of fluoride in these waters
throughout the initial years during which fluoride was added to the water supply,
without it being possible to establish broad-scope geographical patterns, to
later tend toward stabilization during the final years of the time period in
question, in which solely the municipalities supplied by the Letur treatment
plant (which supplies the central and northwestern areas of the Region) showed
levels nearing 0.8 mg/l, been maintained, which are those stipulated under the
regulations resolving in favor of the addition of fluoride. CONCLUSIONS: We can
conclude that only a portion of the municipalities of the Murcia Region has
reached the optimum value for the concentration of fluoride in drinking water
proposed by the Autonomous Community (0.8 mg/liter), or values close to it (0.6
0.7 mg/liter) during the period studied.
PMID- 9643065
TI - [Readmission rate at a regional hospital].
AB - BACKGROUND: The purpose of this study is that of describing the frequency of re
admissions at the "Punta de Europa" Hospital in Algeciras. METHODS: The source of
information employed was that of the Minimal Basic Hospital Admission Data Set
(MBHADS) for 1995-1996, a total of 24,613 cases of hospitalization being
analyzed. Re-admission has been defined as any admission entailing an identical
major diagnosis within the 30 days following release from the hospital. A
descriptive analysis has been made of the variables of age, sex, the unit/ward to
which admitted and major diagnosis involved employing conventional single
variable techniques. RESULTS: The 30-day re-admissions rate was 5% (IC95% 4.8
5.2), totaling 3.4% (IC95% 3.2-3.6) if only the emergency re-admissions are taken
into account. A higher probability of re-admission is related to males, to an
older age to certain diagnoses and to the units/wards to which admitted. The
units/wards showing the highest percentage of re-admissions were the Psychiatric
Ward, Hematology and the Otolaryngology. The Units/Wards showing the lowest
percentages of re-admissions were Ophthalmology, Traumatology and Obstetrics. The
most frequent re-admissions diagnoses were: impending childbirth, AIDS and
complications thereof, neoplasia of the bladder, unstable angina pectoris and
paranoid schizophrenia. CONCLUSIONS: Hospital re-admissions are a useful
indicator of the quality of health care which must be continued to be researched
in our country, particularly after its having been included as an indicator of
the public hospital program contracts in Andalusia. It is also deemed necessary
to improve the definition of re-admission in said program contracts.
PMID- 9643066
TI - [Quality and characteristics of antibiotics prescriptions in an emergency
hospital service].
AB - BACKGROUND: To assess the quality of the prescribing of antibiotics to patients
treated at a hospital emergency department (HED). METHODS: Retrospective study of
the 8600 patients treated and released from a HED throughout the January-April
1996 period. Those patients for whom antibiotics were prescribed as stated on the
release form were included. The parameters employed for assessing the prescribing
quality were: illness subject to being treated with antibiotics, proper
antibiotic, dosage, proper frequency and length of time over which the antibiotic
is to be taken. Each one of these parameters was assigned a mark affording the
possibility of quantifying quality on a 0-100 point scale. The assessment of the
extent to which proper treatment was prescribed was made based on the
recommendations described on four guides to the use of antibiotics. RESULTS:
Antibiotics were prescribed to 609 (7.1%) of the patients, basically for treating
urinary tract infections (17.7%), the prevention of wound infection (13.1%) and
for the treatment of repeated attacks of chronic obstructive pulmonary disease
(COPD) (10.3%). The antibiotic most often prescribed was cloxacillin (22.5%),
followed by ciprofloxacin (13.4%) and clarithromycin (13.2%). Of all of the
patients treated with antibiotics, 10.8% had no illness or any indication subject
to being treated with these medications, and 32% of those patients who did indeed
meet these requirements were prescribed an unsuitable antibiotic. Pneumonia was
the illness for which the best quality of treatment was provided. The average
mark for the prescriptions did not total 80 points in any of the guides.
CONCLUSIONS: Antibiotics are medications frequently prescribed in HED's. Major
errors are found to exist with regard to the indication, selection and length of
the treatments initiated with these medications, as a result of which it is
advisable that sustained educational measures be taken.
PMID- 9643067
TI - [Coverage and immune response to hepatitis B vaccine in adolescents of the
Guadalajara province].
AB - BACKGROUND: Hepatitis B comprises one of the major health problems worldwide. One
of the measures for the prevention thereof is the massive vaccination of
adolescents. The purpose of our study is that of assessing the degree of coverage
of the systematic hepatitis B prevention campaign among the 8th-grade population
in the province of Guadalajara in addition to studying the immune response of
said population, relating said response to other variables. METHODS: Cross
sectional study. The degree of coverage of the vaccination campaign was studied
throughout the entire target population in the province in question. For the
study of the immune response, a sample of 338 students was taken by systematic
random sampling. The titres of anti-HB's were quantified 6 months following the
third dosage, levels of 10 mU/ml or above being considered as being levels
providing protection. RESULTS: The percentage of students properly vaccinated
totaled 82.7%. The overall serum protection rate was 97.5%, and 46.7% of the
sample responded showing titres of over 100 mU/ml. A statistically significant
inverse relationship (p < 0.001) existed between the level of anti-HB's and the
Quetelet level, we not having found any significant differences between the two
sexes on comparing the postvaccination titres of anti-HB's. CONCLUSIONS: We
consider the degree of coverage provided to be satisfactory and the immunogenic
aspect of the vaccine to be good. Obesity is a factor providing a prior
indication of a minor response to the same. This response is not influenced by
the subject's sex.
PMID- 9643068
TI - [Occupational accidents at an Acute Care Hospital].
AB - BACKGROUND: To obtain a better knowledge of the determining factors and
circumstances giving rise to occupational accidents will foster the
implementation of corrective measures. The aim of this study is that of
describing the trend of occupational accidents (OA's) over the course of time and
of determining the risk factors regarding workers being forced to take time off
for sick leave at the "Dr. Peset" Hospital in Valencia. METHODS: Description and
retrospective analysis of the occupational accidents having occurred at the "Dr.
Peset" Hospital in Valencia throughout the 1992-1995 period. The trend and
seasonality of the series (seasonal indexes, SI's) were estimated by
deterministic methods. A logistic regression model was employed to identify the
factors providing a prior indication workers being off on sick leave and to
determine the probability of the occurrence thereof. RESULTS: The highest OA
rates were found among the kitchen and laundry workers (10.00 OA's per 100
workers/year). The OA's involving sick leave continued to show a trend of around
zero, February being the months showing the highest SI (SI = 139.8). Those
processed without sick leave showed an upward trend (r2 = 0.23, p < 0.0001), May
being the month involving the largest number of casualties (SI = 134.2). The
probability of an accident resulting in a worker being forced to take time of for
sick leave increases significantly with age, when the accident in question takes
place in the afternoon/evening, if it takes place in the kitchen/laundry, and if
a sprain or tendinitis is involved. CONCLUSIONS: The measures taken involving the
number of casualties entailing OA's which result in temporary incapacity should
revolve around the less-skilled positions and the kitchen and laundry
departments.
PMID- 9643069
TI - [Analysis of a disease outbreak of brucellosis in slaughterhouse workers].
AB - BACKGROUND: The appearance of an exceptional number of cases of Brucellosis at
the end of 1996 in workers at a slaughterhouse led us to suspect an epidemic
outbreak among this group. This study shows the methodology followed in the
analysis of this outbreak as well as the results obtained. METHODS: 1.
Epidemiological description of the outbreak: number of animals with brucellosis
slaughtered, collection of information from different sources on the number of
those affected: from the mutual insurance company, the record of working days
lost, an epidemiological monitoring system and a survey amongst the workers. 2.-A
case and control study was designed in order to determine, firstly, non
occupational risks--ingestion of fresh cheese or milk and care of animals--and
secondly, occupational risks, depending on the job normally undertaken. 3.-To
verify this a retrospective cohort study was designed. The exposed group was made
up by workers in the slaughter area and the unexposed group comprised the
remainder: any worker giving a positive result to the Rose of Bengal test and IgM
brucellosis antibodies in serum was considered as a case. RESULTS: The
description of the outbreak enabled us to establish that the cases occurred at
the moment when most animals were slaughtered, that only occupational risks were
relevant, that there were more symptomatic cases than notified ones, and that the
slaughter line operators showed higher rates of attack than the remainder of the
workers. CONCLUSIONS: This study analyses the possible causal relationship
between analyzed exposure and the appearance of cases of brucellosis in workers-
a fact which backs the existing scientific evidence on the importance of the
respiratory tract as a mechanism of transmission of this disease in the
workplace.
PMID- 9643070
TI - [Food habits of school children in a Cordoba health district].
PMID- 9643071
TI - [Prevalence of anemia in pregnancy, Pucallpa Regional Hospital, Peru].
AB - Population based health surveys in Peru show that the general fertility rates,
proportion of pregnant adolescents, and maternal and child morbidity are higher
in the jungle regions than in other parts of the country. Endemic intestinal
parasitic diseases increase the risk of anemia in pregnant women already
suffering from iron, folic acid, and other nutritional deficiencies. This is the
most common complication of pregnancy in many Latin American countries and is
often associated with premature labor, low birthweight, and perinatal mortality.
There are very few studies on this subject based on jungle populations and no
reliable estimates of the prevalence of anemia in local pregnant women. The
present study was designed to determine the prevalence of anemia in pregnant
women attending the Regional Hospital in Pucallpa, located in the Peruvian
jungle, from January 1993 to June 1995. This cross-sectional study, which was
based on the registries of prenatal and childbirth services encompassing 1,015
pregnant women, looked into the potential association between anemia and such
variables as the mother's chronological age, schooling, previous pregnancies, and
weight at the beginning of pregnancy. Maternal hemoglobin levels were compared
with the newborns' weight at birth. The prevalence of anemia in this population
sample was 70.1%. This value was not modified when adjusted for maternal age,
schooling, or interval between births. Anemia prevalence was directly related to
the number of previous pregnancies and inversely related to weight gain during
pregnancy. The perinatal mortality rate was 37.7 per 1,000 births. Neither this
rate nor the birthweights were associated with the mother's degree of anemia. A
multivariate regression analysis showed that maternal body weight at the start of
pregnancy (P = 0.0001), weight gain during pregnancy (P = 0.0001), and the number
of pregnancies (P = 0.008) are predictors of birthweight. Results showed that the
high prevalence of anemia in Pucallpa's pregnant women is not associated with low
birthweight or a high perinatal mortality rate. Future studies should investigate
the principal causes of anemia in the pregnant women of Pucallpa and how the
disease affects the psychomotor development of their offspring.
PMID- 9643072
TI - [Perceptions regarding leprosy and resulting handicaps prior to diagnosis in
Recife, Brazil].
AB - This article reports on a case-control study conducted in Recife, Brazil, between
November 1993 and July 1994, to determine how leprosy patients' perceptions and
notions influence disease management and use of health services. The sample was
composed of 183 residents of Recife between the ages of 20 and 70 years who
sought diagnostic services in the dermatology clinics of two referral centers
situated in the third, fourth, and sixth political and administrative regions.
Sixty-four patients having handicaps or their precursor lesions were classified
as cases; the remaining 119 were used as controls. All were diagnosed during the
study period. For the analysis, adjustments were made for sex, age, schooling,
and a previous history of Hansen's disease among patients. The study revealed the
simultaneous presence of two types of "invisibility" of the disease in an area
where endemicity is increasing: 1) for patients in both groups, the low frequency
of spontaneous explanatory models related to the illness, even in the presence of
disease, and 2) for health professionals, the limitations of detection methods.
Since such deficiencies affect decisions bearing on individual and collective
disease management, they are a risk factor in and of themselves and stand in the
way of eliminating leprosy as a public health problem.
PMID- 9643073
TI - The use of capture-recapture methods to monitor diabetes in Dominica, West
Indies.
AB - The aim of this project was to evaluate the utility of capture-recapture (CR)
estimation methodology, together with easily accessible sources of information,
for monitoring the frequency of diabetes mellitus in a developing country. On the
Caribbean island of Dominica, from July 1995 through July 1996, the names were
collected of all individuals who were listed in at least one of three sources as
having been diagnosed with diabetes during 1995. The sources were the membership
list of the Dominica Diabetic Association, a register of patients in seven
regional health centers, and clinic records of the Princess Margaret Hospital,
which is the main hospital on the island. Capture-recapture techniques were used
to estimate the number of Dominicans with diagnosed diabetes who were missed by
all three sources of information and to evaluate dependencies among the sources.
An ascertainment-corrected prevalence estimate of diagnosed diabetes was then
calculated. The three sources identified a total of 1,945 different individuals.
When this number was compared with the ascertainment-corrected estimate obtained
with CR methodology (2,688), it appeared to represent only 72.3% of the true
prevalence of diagnosed diabetes. Most of the under-ascertainment by the data
sources was due to cases that were missed in the urban area of the island. This
approach to disease monitoring may be useful for other Caribbean countries.
However, standardized procedures for collecting and reporting prevalence and
morbidity data are needed to maximize its accuracy and cost-effectiveness.
PMID- 9643074
TI - [Cytopathological test coverage in the city of Pelotas, Brazil].
AB - In 1995, cervical cancer was the fourth most important cause of death among women
in the state of Rio Grande do Sul, Brazil. There are no available studies on Pap
smear examination coverage in Pelotas, which is the largest city in the southern
part of Rio Grande do Sul. Accordingly, in 1992 a population-based, cross
sectional study was carried out among 20 to 69 year-old women residing in urban
areas of the city. The objectives of the study were to ascertain any Pap smear
testing in the 3 years prior to the study, to determine the coverage of cervical
cancer screening, and to identify any factors associated with the performance of
Pap tests in Pelotas. Social class was chosen as the determining variable. To
categorize social class, two classifications were used: Bronfman's classification
and the classification used by the Brazilian Association of Market Research
Institutes. Among the 934 women interviewed, 606 (65%) had had a Pap smear test
in the 3 years before the study. The multivariate analysis revealed significant
differences regarding performance of such tests in terms of social class, age,
and frequency of medical consultations per year. No significant differences were
found in terms of education, type of health service used, or hospitalizations
during the year prior to the study. This study reveals that coverage of cervical
cancer screening for women between 20 and 69 years of age in Pelotas is higher
than the coverage found in other parts of the country or even of the world.
However, for women in lower social classes, coverage was found to be between 52
and 56%. These data can contribute to the development of measures aimed at
increasing cervical cancer screening among specific sectors of the population.
PMID- 9643075
TI - [Risk factors for low birth weight].
AB - Low birthweight (LBW) is the main known determinant of infant mortality. In spite
of the sharp decrease in infant mortality rates and of the rise in survival rates
for children with LBW, no important decrease in LBW rates has been observed in
Neuquen, Argentina. The purpose of this study was to try to understand the risk
factors for LBW, the frequency of LBW in the population, and the role of prenatal
care in its prevention, as well as to develop a risk factor scale that could be
used to identify women at higher risk of giving birth to a child with LBW. With
this in mind we performed a cross-sectional study based on 50% of the data
entered into the Perinatal Information System for 1988-1995 by the 29 hospitals
in Neuquen province (46,171 births). The distribution of birthweight and the
frequency of potential risk factors for LBW were examined. The relationship
between such factors and LBW was studied using a logistic regression model. On
the basis of the results obtained, an additive scale was drawn up and validated
with the remaining 50% of the data for registered births. The highest odds ratio
(OR) was seen in women who had no prenatal care (OR = 8.78; 95%CI: 6.7 to 11.4).
ORs for inadequate prenatal care, lateness in attending the first prenatal visit,
preeclampsia or eclampsia, hemorrhage and anomalies of the placenta or placental
membranes, and a history of a previous child with LBW were greater than 2.0. The
risk of having children with LBW was also higher in women over the age of 40,
women under 20, single women, smoking mothers, women with an intergenesic
interval of less than 18 months, and women with a body mass index of less than
20. Finally, there was a direct linear relationship between points on the risk
scale and the risk of having a LBW infant.
PMID- 9643076
TI - Flit-gun sprayer characteristics.
AB - Six flit-gun sprayers were tested for possible use in mosquito adulticide
programs where inexpensive nonmotorized application technology may be required.
An analysis of variance for differences in droplets < or = 24 microns (mu),
droplets > or = 48 mu, droplets/cm2, volume median diameters, and mosquito
mortality is provided. As shown by these data, good results can be achieved with
this equipment.
PMID- 9643080
TI - [The Foundations of Bioethics by H. Tristram Engelhardt Jr.: comments on James F.
Drane's review].
PMID- 9643081
TI - Public health services: should they respond to demand or necessity?
PMID- 9643084
TI - [Stress proteins: expression of a universal phenomenon of cell defense].
AB - Heat shock proteins or stress proteins play a role in adaptative thermotolerance.
All cells, procaryotic and eucaryotic, are able to respond to different cellular
aggressions by the synthesis of these stress proteins. In normal physiological
conditions, they are considered as "molecular chaperones" Their actual role in
pathology is still unknown; some of these heat shock proteins may be correlated
with the degree of aggressiveness of some tumors.
PMID- 9643085
TI - [Re-evaluation of immunomodulator treatments for recurrent abortions].
AB - Immunotherapy of spontaneous recurrent abortion is still a matter of controversy.
Since 1985, 117 patients were treated in our center. Transfusions of paternal
leucocytes (PL) were given to 56 patients and intravenous immunoglobulins
(i.v.Ig) to 61 patients. The allocation of the two treatments was not randomised.
Respectively 74% and 71% normal pregnancies were achieved. In two cases treated
by paternal leucocytes, the appearance of anti-erythrocytes alloantibodies (anti
c and anti Jkb + C) was noted. Two patients receiving i.v.Ig had a transient
allergic reaction (urticaria). In the five patients presenting with spontaneous
abortion in the setting of in vitro fecondation, four normal pregnancies were
achieved. These encouraging results from a single center are still to be
considered as preliminary but urge us on continuing this approach. One of the
drawback of i.v.Ig is their cost. Use of paternal leucocytes constitutes an
adequate alternative provided that a strict immunological selection of the father
is performed to avoid lymphocyte or platelet alloimmunisation. Our results are
discussed in the light of recent controlled studies emphasizing the importance of
the placebo effect and in the light of the new concepts in pregnancy immunology
(protective action of trophoblastic HLA-G and Th2 cytokines; antagonistic effect
of endometrial NK cells.
PMID- 9643086
TI - [Pneumococcal spondylodiscitis. A case report].
AB - We report on a case of a 66 years-old patient suffering weight loss and lumbar
pain, localized at L2-L3. A spondylodiscitis was revealed by CT and MRI;
intervertebral disc puncture was positive for Pneumococcus Pneumoniae. The
clinical evolution was good with the anti-bacterial treatment, while the patient
developed a synostosis L2-L3. Incidence, bacteriology, imaging and therapy of
spondylodicitis are discussed.
PMID- 9643087
TI - [Anatomo-clinical conference: pulmonary cancer and cerebral vascular accident].
AB - A patient with a lung adenocarcinoma died shortly after a first chemotherapy
course from multifocal neurological lesions and severe cardiopathy. Autopsy has
revealed the cause of these complications.
PMID- 9643088
TI - [Transdermal fentanyl].
AB - Fentanyl is a synthetic pure opioid agonist with a selective activity on mu
receptors. Its high liposolubility allows a transdermal administration, using a
Transdermal Therapeutic System (TTS). The clinical efficacy is widely
demonstrated in the field of cancer pain control. The side effects are those
observed with morphine but with less frequent constipation. The adjonction of a
short acting morphine in case of acute pain is recommended.
PMID- 9643089
TI - [Conductive deafness: anatomo-radiological correlation].
PMID- 9643090
TI - [The problem of euthanasia legislation].
PMID- 9643091
TI - [What is your diagnosis? Spontaneous pneumomediastinum (mediastinal emphysema)].
PMID- 9643092
TI - [Dog, cat and human bites].
AB - Animal and human bites carry a high risk of infectious complications. Human bites
and in particular clenched-fist injuries as well as cat bites are highly prone to
infection as are wounds that involve the hand or deep structures including
joints, bones and tendons. The management of bite wounds consists of intensive
irrigation with large volumes of normal saline and a cautions debridement of
devitalized tissues. Generally, it appears prudent to leave the wounds open,
however, in cases carrying a low risk of infection, a primary surgical closure
might be appropriate. If a bite wound is infected, an antibiotic course with
amoxycillin/clavulanic acid (first choice) or tetracyclines (second choice) for
10-14 days is recommended. In patients who present early after the injury, an
antibiotic prophylaxis for 3-5 days is appropriate, particularly when the risk
for the development of infection is high. Furthermore, a tetanus booster and in
case of possible transfer of rabies, a rabies vaccination with immunoglobulins
and inactivated virus preparation is recommended.
PMID- 9643093
TI - [Acute therapy of ischemic stroke].
AB - Ischemic stroke is a neurological emergency as transition form reversible to
irreversible lesions of the brain may be prevented by starting the therapy within
six hours after the onset of the neurological deficits. Intravenous thrombolysis
may be administered within the first three hours and intraarterial thrombolysis
within the first six hours after considering inclusion and exclusion criteria.
Neuroprotective drugs are under investigation and may enlarge the spectrum of
acute therapy in the near future. Ischemic strokes that do not qualify for
thrombolysis may be treated with unfractionated heparin, aspirin or low-molecular
weight heparin. Indications for the administration of antithrombotic drugs are
discussed. Blood pressure is frequently elevated in acute ischemic stroke, but
rarely needs therapy or careful lowering. Fever, hypo- und hyperglycemia,
epileptic seizures and intracranial hypertension should be treated.
PMID- 9643094
TI - [Cool, clever, established--variations on anxiety defenses in today's society].
AB - Anxiety is a psycho-biological phenomenon, psychologically manifested in feelings
of constrainment, threat, and vulnerability; and physically in evidence of
increased sympathetic tone. Three phenomenologically different forms of anxiety
can be distinguished (real anxiety, existential anxiety, neurotic anxiety).
Existential anxiety is based on four themes: self-development, self-submission,
change and finality. Anxiety and anxiety defences are a part of human existence.
Every culture develops its own rituals for defending against anxiety. Three
variations of anxiety defence are described which typically appear in affluent
societies: coolness, cleverness and happiness. These strategies are, depending on
the situation, sensible and advantageous in dealing with, perceiving, overcoming
and defending against existential anxieties.
PMID- 9643095
TI - [Diagnosis and assessment of anxiety disorders].
AB - Anxiety disorders tend to become chronic if untreated and often have considerable
social consequences. Therefore, early recognition of anxiety disorders at the
primary health care level is of great importance. This article gives a short
overview of important aspects of the diagnosis of anxiety disorders in general
medical practice. Panic disorder, generalised anxiety disorder and phobic
disorders are describer and phobic disorders are described based on ICD-10
criteria. Anxiety disorders have important differential diagnostic distinctions
from somatic disorders and other psychiatric disorders. A diagnosis of panic
disorder can be easily missed if physical symptoms are predominant. Also, there
is a high comorbidity with depressive disorders, substance-abuse and -dependence
and suicidality. Furthermore, during the assessment procedure the topics of
psychosocial life situations, social effects and earlier treatments should be
investigated.
PMID- 9643096
TI - [Therapy of anxiety disorders in family practice].
AB - A treatment algorithm for anxiety disorders in primary care practice is
introduced. Anxiety is understood as a complex pattern which consists of
thoughts, emotions, behaviour and physiologic reactions. Patient education is
outlined as a crucial factor for the management of anxiety. Some examples of
patient education are given. The most important pharmacological agents for the
treatment of anxiety are benzodiazepines, antidepressants and buspirone. The drug
treatment of some common anxiety disorders is presented. Finally the limits of
anxiety management in primary care are discussed and some techniques of cognitive
behaviour therapy are outlined.
PMID- 9643097
TI - [Progressive decline in athletic performance].
AB - A 48-year old engineer presented with progressive decline in sports performance.
A history of latent hypothyroidism was known since 3 years. Adrenocortical
insufficiency was suggested and confirmed by further investigations. Because of
additional autoimmune thyroiditis and family history with autoimmune diabetes of
the son, the diagnosis polyglandular autoimmune syndrome type II was made.
PMID- 9643098
TI - [Subarachnoid hemorrhage in aneurysm of the left anterior cerebral artery].
PMID- 9643099
TI - [Mild von type I von Willebrand disease].
PMID- 9643100
TI - [The effect of the unilateral exclusion of nasal breathing on skull development
in an experiment].
AB - Unilateral disturbance of nasal respiration was modeled in albino rats. All
animals developed deformations of the skull in the sagittal and transversal
planes. The pathogenesis of deformations is connected with neurotrophic disorders
and injury to the nasal cartilaginous structures responsible for the skull
growth.
PMID- 9643102
TI - [The microhardness of dental tissues as an index of their normal functional
stability and in pathological states].
AB - Microhardness of dental tissues was assessed. Hard tissue specimens from 65 teeth
removed for medical indications were examined. The enamel microhardness is 30-40%
decreased in caries, whereas dentine is virtually intact. Depulpation decreases
the enamel microhardness by 23-26%, while the microhardness of dentine is changed
negligibly (by 1-1.5%).
PMID- 9643101
TI - [Clinico-laboratory studies of the properties of Aquafresh toothpaste].
PMID- 9643103
TI - [A comparative analysis of the use of Uzor and Optodan laser apparatus for the
prevention and combined treatment of pulpitis and periodontitis].
AB - Clinical research 242 patients for comparison purposes of efficiently of
employment of semiconductor laser apparatus "Uzor" and "Optodan" as
physiotherapeutic of the factor for preventive maintenance and treatment of
complications, arising the ambassador endodontic of treatment is spent. Results
of application of semi-conductor laser apparatus are resulted at the various
forms pulpitis and periodontitis. Significant reduction of a pain directly after
a procedure LSL is marked. The highest efficiency is established by use of the
apparatus "Optodan", connected with distinction configurations of a impulse.
PMID- 9643104
TI - [A comparative evaluation of the efficacy of the conservative treatment of
chronic apical periodontitis in patients with secondary immune deficiency and in
somatically healthy persons].
AB - The efficacy of conservative treatment of chronic apical periodontitis is
compared is somatic patients and somatically healthy subjects. Twenty-seven
patients with chronic obstructive bronchitis and secondary immune insufficiency
and 31 patients without underlying diseases were treated. Conservative treatment
of chronic apical periodontitis was insufficient in the patients with secondary
immunodeficiency.
PMID- 9643105
TI - [Cytological indices as criteria for assessing periodontal status].
AB - The authors define the complex of criteria for analysis of cytograms of gingival
impressions in health and periodontal diseases. Such criteria are needed for
objective diagnosis and monitoring of periodontal status over the course of
treatment. All the cellular elements were taken account of: different types of
epithelial cells, including those with signs of cytopathology and bacterial
contamination, connective tissue cells, mononuclears, leukocytes, and
fibroblasts. The cytological picture correlated with the status of periodontium
and forms and severity of pathological processes developing in it.
PMID- 9643106
TI - [The comparative efficacy of nonsteroidal anti-inflammatory agents in the
combined treatment of periodontal diseases].
AB - Nonsteroid anti-inflammatory drugs (NAID) are compared in 120 patients with
periodontitis. The results confirmed clinical efficacy of modern NAID in this
patient population. The best clinical results were achieved with voltaren. Local
anti-inflammatory efficacy of dressings with acetylsalicylic and orthophene
ointments and pyroxiphene was virtually the same.
PMID- 9643107
TI - [The effect of different concentrations of dimexide and ortofen on the T-cell and
neutrophil components of immunity].
AB - Clinical and immunological efficacy of 2.5% orthophene and 50% dimexide used to
arrest an acute inflammatory process in the periodontium is assessed. Three types
of salivary neutrophils are distinguished, similar to previously detected types
of response of blood immunocompetent cells. Both drugs had a favorable impact on
the functional activity of blood T-lymphocytes, blood and salivary neutrophils
and are recommended for patients with types I and II reactions of immunocompetent
cells of the blood.
PMID- 9643108
TI - [The immune and dental status of women who have given birth to infants with
intrauterine growth retardation].
AB - Secondary immunodeficiency was detected in women who gave birth to small-for-date
newborns. This state was one of the causes of periodontal and hard dental tissue
involvement. Women with small-for-date fetuses are at risk of dental diseases.
PMID- 9643109
TI - [The clinico-morphological basis for the combined treatment of lichen ruber
planus of the oral mucosa using Solcoseryl].
PMID- 9643110
TI - [A method for the surgical treatment of pericoronitis using a computerized laser
apparatus].
AB - Use of pulsed exposure to CO2 laser permits operations on soft tissues of the
oral cavity with the minimal injury. The choice of optimal parameters of laser
exposure depends on the stage of the inflammatory process. The proposed ablation
regimen for the treatment of pericoronitis notably accelerates the treatment and
decreases the amount of drugs used. The absence of complications after the
operation and a shorter rehabilitation period recommend the Lancet computer-aided
laser for dissection of the veil.
PMID- 9643111
TI - [A comparative evaluation of the efficacy of the isolated and joint use of
dioksizol and low-frequency ultrasound in the combined treatment of phlegmons of
the maxillofacial area].
AB - The effects of dioxycol and low-frequency ultrasound alone and in combinations on
the microflora of suppurative wounds formed after opening of maxillofacial
phlegmons are assessed in 142 patients. Clinical and laboratory findings indicate
a higher efficacy of combined use of these treatment modalities, which are
recommended for optimal local treatment of purulent maxillofacial wounds.
PMID- 9643112
TI - [The new potentials for reconstructive restoration in defects of the lower lip
after cancer operations].
AB - Eleven patients with cancer of the lower lip were treated in 1995-1996. The first
stage of treatment consisted of radiotherapy, the second one of resection of the
lower lip with replacement of the defects with a dermatocutaneomucous flap from
the cheek, including all anatomical components and hence permitting anatomically
full-value repair of the lower lip. The method is reliable and effective.
PMID- 9643113
TI - [The disinfection of impressions to prevent hospital infections. Sodium
hypochlorite as a disinfecting agent].
AB - Effect of sodium hypochlorite disinfection of impressions on the size and quality
of plaster models is studied. Twenty-minute submerging of silicone impressions in
0.5% sodium hypochlorite solution did not change their size and did not
deteriorate the quality of surface and hardness of plaster models. Stomalgin
impressions cannot be disinfected by sodium hypochlorite solution because of
expressed destructive effect of this disinfectant on the impressions.
PMID- 9643114
TI - [The characteristics of the muscular activity of the maxillofacial area in
persons with partial tooth loss depending on the extent of the dentition defect].
AB - The electromyogram (EMG) amplitude of the masticatory and temporal muscles is
decreased and EMG amplitude of suprasublingual muscles increased during
mastication or voluntary occlusion in patients with class I dentition defects in
comparison with the controls. The changes were the greater, the more antagonist
pairs were missing. The duration of masticatory period and the number of
masticatory movements increased. The most notable changes in the muscular
activity are observed in subjects with 4 antagonist pairs missing.
PMID- 9643115
TI - [The clinical manifestations of the electrochemical processes due to the
finishing treatment of dentures made from stainless steel].
AB - The authors propose to treat stainless steel dentures by grinding on
organosilicon binding followed by 2 polishing procedures: with diamond paste and
paste based on ultradispersed aluminum oxide powder. This technology improves the
corrosion resistance of dentures and eliminates signs of diseases caused by
electrochemical processes in the oral cavity more effectively than basic
technology (vulcanite grinding and polishing with GOI paste).
PMID- 9643116
TI - [Occlusal anomalies in the deciduous and mixed bites].
AB - In 311 examinees (177 boys and 134 girls) with primary dentition and 535
examinees (285 boys and 250 girls) with mixed dentition in Istria--Croatia, the
frequency of orthodontic and occlusal anomalies in regard of space plane and
premature extraction of c, m1 and m2 are investigated. The orthodontic anomalies
are fortified in 46.95%, premature loss in 11.25% and occlusal anomalies in
40.83% of examinees with primary dentition, while in mixed dentition the 58.69%
of examinees have orthodontic anomaly, the 17.20% premature loss and the 48.97%
of examinees have occlusal anomaly. In both phases of dentition the most frequent
are occlusal anomalies: combination of sagittal-vertical plane, and those in
sagittal and vertical space plane respectively.
PMID- 9643117
TI - [The use of the Optodan laser physiotherapeutic apparatus for the prevention of
complications and the acceleration of the time in treating anomalies in the
position of individual teeth with fixed orthodontic appliances].
AB - Physiotherapy including laser exposure was used in the treatment of 243 patients
aged 13-34 years with abnormal occlusion. The results indicate that laser
exposure effectively relieved pain after fixation and activation of permanent
orthodontic devices, treated gingivitis before and during orthodontic treatment,
prevented exacerbations of periodontitis, and accelerated eruption of retained
teeth.
PMID- 9643118
TI - [An automated computer system for the differential diagnosis and laser treatment
of benign neoplasms and tumor-like masses in the oral cavity].
AB - Automated computer system for differential diagnosis and defining the indications
for pathogenetic therapy is described, which was used in 2816 patients and was
effective in 97% of cases. The system includes computer-regulated Lancet surgical
lasers (wavelength 10.6 microns, power 60 W, frequency 0.05-1.0 Hz) and Optodan
physiotherapeutic laser (wavelength 0.85 micron, power 4 W, frequency 0.08-3
kHz).
PMID- 9643119
TI - [A computerized expert system for the diagnosis and prognosis of the course of
acute odontogenic inflammatory diseases (DIAPRO)].
AB - A computer-aided expert system for diagnosis and prediction of the course of
acute odontogenic inflammatory diseases DIAPRO is created. Based on commonly used
laboratory and clinical parameters, it permits a long-distance diagnosis of acute
maxillofacial inflammations and their complications and provides data for 13
signs of patient's status.
PMID- 9643120
TI - [The morphological pathology of the "double lip" (a clinical case)].
AB - Morphological changes of tissues in patients with macrocheilia or so-called
"double lip" are described. These changes refer this abnormality to teratomas.
Surgical treatment of the condition is discuss.
PMID- 9643121
TI - [Experience in organizing an office for functional diagnosis based in an urban
dental polyclinic].
PMID- 9643122
TI - Shaken baby syndrome.
PMID- 9643123
TI - [HIV epidemic].
PMID- 9643124
TI - [HIV diagnosis 1998].
AB - Due to considerable technical progress during the last few years the diagnosis of
HIV-infection has been substantially improved. Third generation antibody
screening assays, which also detect antibodies of the IgM and IgA type, have
considerably narrowed the immunological window. The determination of the viral
load in peripheral blood employing nucleic acid amplification techniques is now
generally available and used for diagnostic and prognostic purposes as well as
for the monitoring of antiviral therapy. To detect a HIV-infection the antibody
screening assay is primarily used and complemented by the HIV-1 p24 antigen assay
provided an early primary infection is suspected. In the latter case the antibody
screening assay is often negative or indeterminate, while the p24 antigen assay
is positive. According to the 1998 guidelines of the Federal Office for Public
Health, the physician will be informed of the screening assay result without the
need to await a confirmatory test in case of a reactive screening assay in the
first sample. Confirmation, e.g. by immunoblot, will be done in a second blood
sample which should be sent to the laboratory as soon as possible. EDTA-blood is
recommended for this purpose, because it is best suited for quantification of
plasma viremia, which has become a prerequisite for the institution and follow-up
of antiretroviral treatment. The second sample will also serve to exclude false
positive results due to clerical errors, and to determine the type of HIV, i.e.
HIV-1 or HIV-2. The concept outlined should accelerate the availability of
reactive test results to the physician and should reduce the cost of the
diagnostic procedure.
PMID- 9643125
TI - [Sexual transmission of HIV: effect of potent antiretroviral therapy].
AB - The recent progress of our understanding of the pathophysiology of human
immunodeficiency virus (HIV) infection and the availability of new antiretroviral
compounds has markedly improved the prognosis of patients infected with HIV. It
has been postulated as early as 1991 that potent community-wide treatment of HIV
infection could paradoxically lead to an increased spread of the HIV epidemic if
treatment is not associated with a reduced infectivity of HIV. In the past few
years, several groups have demonstrated a good correlation of the quantity of HIV
present in semen with factors that are known to increase the likelihood of sexual
transmission of HIV. A similar correlation has recently been demonstrated for the
presence of HIV in female genital secretions. During the past year, a number of
studies have demonstrated a marked effect of antiretroviral treatment on the
shedding of HIV in the male and female genital tract, indicating a potential role
of antiretroviral treatment for the prevention of HIV infection. Although potent
antiretroviral therapy is beneficial on a public health basis, patients with no
detectable virus in their blood or semen under treatment should not be considered
non-infectious and patients should keep up with safer sex practices.
PMID- 9643126
TI - [Post-exposure HIV prevention within and outside the hospital].
AB - There is a low risk of infection with the human immunodeficiency virus (HIV) for
HCW through exposure in the work place. The mean risk of infection with HIV after
a percutaneous exposure is 0.3%. This risk can be considerably higher depending
on various factors: for example, a deep percutaneous injury or the source patient
being in an end stage of HIV infection. Despite compliance with adequate
precautions, it is not always possible for HCW to avoid injuries. This fact has
made intervention desirable after such exposure. Zidovudine (AZT) was available
as the first effective drug for treatment of HIV infection. Also, animal
experiments have shown efficacy in prophylactic use of zidovudine. Therefore,
since the beginning of the 90's, there has been an increased use of postexposure
prophylaxis with zidovudine for exposed HCW, and during this period of use more
evidence has come up to show the efficacy of PEP. In fact, a large retrospective
case-control study showed a 81% reduction of HIV transmission to exposed HCW in
the zidovudine treated group after percutaneous exposure. Based upon this
impressive evidence and other data which indicate the efficacy of PEP,
postexposure prophylaxis has become a standard procedure in the health care
setting after a significant exposure to HIV. A combination of three
antiretroviral drugs, usually including a protease inhibitor, is used today.
Based on our current pathogenetic understanding, PEP should be started as soon as
possible after exposure to HIV. There are effective tools for preventing HIV
transmission in the general population. However, these tools do not provide
universal protection: rupture of condoms, needle sharing and unprotected
intercourse with a HIV infected person are situations at risk of HIV
transmission. In spite of a different mode of exposure when compared to the
health care setting, PEP in timely application is believed to be efficacious. To
date there is no controlled data to support PEP in such situations; however, PEP
with a combination of antiretroviral drugs after anal, oral (with ejaculation) or
vaginal intercourse and needle sharing with a HIV-positive partner is recommended
for a minimum of two weeks. There are reservations in recommending PEP after
unprotected sexual intercourse with a partner of unknown serostatus.
PMID- 9643127
TI - [Emergencies in HIV infection].
AB - Emergencies in HIV-infected patients are a common complication which may occur at
any stage of the disease. Opportunistic infections may lead to irreversible
damages of organs such as the brain, the eye or the lung. With the widely use of
antiretroviral therapy side effects of reverse transcriptease inhibitors and
proteinase inhibitors and drug interactions are frequent causes of severe
symptoms such as nausea and diarrhoea or of complications such as anaemia or
leucopenia. As with Non-HIV-associated emergencies empiric therapy may be
necessary to treat patients to prevent severe organ damage.
PMID- 9643128
TI - [Prevention of opportunistic infections in HIV-infected adults].
AB - Opportunistic infections have a major influence on morbidity and mortality in HIV
infected individuals. Prophylactic measures have to be introduced for each
patient, corresponding to the stage of disease measured by CD4-lymphocyte count.
They consist of exposure prophylaxis, vaccinations and especially
chemoprophylaxis with antimicrobials. Some live vaccines are contraindicated in
HIV infected patients. Pneumococcal vaccine for every patient and specific
primary prophylaxis against pneumocystis carinii pneumonitis, cerebral
toxoplasmosis and M. avium infection in patients with manifest immunodeficiency
improve survival and quality of life of many patients. After most opportunistic
infections, secondary lifelong antimicrobial prophylaxis is indicated. In future,
indications of primary and secondary prophylaxis have to be redefined in the
light of the new antiretroviral combination therapies.
PMID- 9643129
TI - [Clinically significant drug interactions in HIV-infected patients].
AB - In recent years the availability of highly active antiretroviral therapies and
prophylaxis and treatment of opportunistic infections in patients with HIV
disease have reduced morbidity and mortality. Many different drugs may be
prescribed in a patient simultaneously. Therefore, the potential for interactions
between different substances is increased. The possible mechanisms of drug
interaction concern pharmakokinetics (absorption, metabolism, elimination) and
pharmakodynamics. They can lead to significant changes in plasma concentrations
and may affect efficacy and toxicity of a drug. One of the most important
mechanisms of interaction is the inhibition or induction of the hepatic
cytochrome P-450 enzyme system. All protease-inhibitors are metabolized by
CYP450, mostly by the subunit 3A4. Proteinase-inhibitors are themselves very
potent inhibitors of CYP4503A4 and increase the concentration of drugs
metabolized this way. This article summarises the most important mechanisms of
drug interactions and demonstrates the most frequent and clinical significant
consequences.
PMID- 9643130
TI - [Decision guides for antiretroviral treatment in pregnancy].
AB - HIV-infected adults can now be offered highly active antiretroviral combination
therapies. Major advances in understanding the pathogenesis of HIV-infection have
led to earlier onset of treatment during the course of HIV infection. Most of the
new antiretroviral drugs are not approved for use in newborns and infants.
Zidovudine monotherapy during pregnancy, during labor and for the newborn, has
been shown to reduce vertical HIV transmission by almost 70%. Zidovudine
monotherapy is at present considered obsolete for the treatment of HIV-infected
adults. Thus, during pregnancy, both the interests of the HIV-infected mother and
the fetus/newborn must be taken into account. Clinical data to solve this dilemma
are not available. In general, standard antiretroviral treatment should not be
withheld from pregnant HIV-infected women, but prescription has to be the result
of careful discussion of the risks and benefits of such treatment during
pregnancy. The final decision about treatment, whether primarily for the mother,
to reduce vertical transmission or both, has to be taken by the pregnant women.
This discussion and information must involve physicians with important experience
in the treatment of HIV-infected patients.
PMID- 9643131
TI - [The Swiss HIV Cohort Study--a link between clinical research and medical
practice].
AB - The prospective Swiss HIV Cohort Study (SHCS) documents since 1988
epidemiological, clinical and laboratory data of HIV-infected participants. Until
the end of 1997, 9447 patients with a total follow-up of 25,584 patient-years
have been included. The proportion of women is 27.3% and is rising. The
proportion of heterosexually infected patients has been rising since 1992, this
group was with 35.6% in 1997 the most frequent transmission category within the
newly registered participants. The SHCS is representative for Switzerland since
73% of the 5532 nationwide registered AIDS cases are included in the study.
Recently, the SHCS data could demonstrate an impressive reduction in morbidity
and mortality due to the improvement in therapy and prophylaxis. The SHCS also
serves as a basis for large multicenter studies that aim to evaluate new
prophylactic treatments or new antiretroviral strategies. By introducing uniform
guidelines for the diagnosis and the treatment of HIV infection, the SHCS has
contributed significantly to the high quality of patient care, a goal that must
be maintained and further improved in the future. Also important is the
recognition of acute HIV infections because early treatment of such patients
holds the promise to substantially improve the clinical course.
PMID- 9643132
TI - [Stress echocardiography--principles, methodology, results and indications].
PMID- 9643133
TI - [Means for optimizing the parameters of physiotherapeutic exposures].
AB - The paper deals with the problem of adequacy of electromagnetic exposure of
biological systems, indicates principal directions of optimization of
physiotherapeutic actions including necessary hard and software, methodology of
registration of the body response to these effects.
PMID- 9643134
TI - [The comparative clinico-physiological characteristics of the action of air
carbon dioxide-radon baths in patients with ischemic heart disease].
PMID- 9643135
TI - [Transcerebral exposure to sinusoidal modulated currents in bronchial asthma
patients].
AB - Clinical examination of 85 patients with bronchial asthma (BA) revealed thyroid
affection proved by ultrasonic and/or hormone profile investigation in 42(49%)
patients. Transcerebral treatment with sinusoidal modulated currents gave rise to
positive trends in external respiration, clinical and biochemical blood indices,
immunity status which appeared more pronounced in BA patients without the
endocrine disorder.
PMID- 9643136
TI - [The use of an aerosol of natural brine and of sinusoidal modulated currents in
chronic pneumonias in children].
AB - Inhalations of 1% natural brine in combination with SMC electrophoresis of 1%
natural brine above the lesion proved to ensure good correction of the defense of
respiratory tract mucosa and to prolong remission to 15-18 months. This method
can be applied in sanatoria, in rehabilitation centers, in pulmonary disease
departments.
PMID- 9643137
TI - [The pelotherapy of patients with periodontitis].
AB - 90 patients with periodontitis have received peloid therapy. Mineral mud from
Lake Goreloye deposits was applied by means of a specially developed device
providing good contact of the mud with the gingiva and teeth. A good clinical
response was achieved.
PMID- 9643138
TI - [The use of laser puncture in the combined treatment of peptic ulcer patients].
PMID- 9643139
TI - [The treatment of patients with chronic intestinal diseases at a balneological
sanatorium].
PMID- 9643140
TI - [The comparative effect of classic massage of different intensities on patients
with chronic salpingo-oophoritis].
AB - Massotherapy in different regimens has been used in 30 patients in remission of
chronic salpingo-oophoritis (CSO). The massage produced positive changes in blood
coagulation, immune status, regional hemodynamics of the small pelvis,
bioelectric activity of the muscles of the anterior abdominal wall and
lumbosacral region. A strong anesthetic and antiinflammatory effect of intensive
massage in 78%, recovered reproductive function in 33% of the patients allow to
recommend intensive massage as possible monotherapy of patients in remission of
CSO.
PMID- 9643141
TI - [The sequential use of cryotherapy and the electrophoresis of nicotinic acid by
sinusoidal modulated currents in the treatment of patients with osteochondrosis
of the cervical spine].
PMID- 9643142
TI - [The types of traction in osteochondrosis of the lumbar spine].
AB - The effects of low-intensive tractions were evaluated clinically and
electrophysiologically in 148 patients with neurological symptoms of lumbar
osteochondrosis. The above tractions were combined with vibration, peloid
electrophoresis and sulphide baths. Indications and contraindications for
tractions are outlined. The above complexes are recommended for use in the
programs of rehabilitation of patients with osteochondrosis of the lumbar spine.
PMID- 9643143
TI - [The use of cardiointervalography for assessing the tolerance for intensified
courses of physiobalneotherapy in patients with osteoarthritis].
PMID- 9643144
TI - [The use of transcutaneous electrostimulation in the treatment of diabetic
angioneuropathy].
AB - Transcutaneous electrostimulation (Amplipul's-4 unit) was used in 29 patients
with diabetes mellitus and diabetic angioneuropathy. The impact was directed to
three fields a session: paravertebral, musculus gastrocnemius, feet.
Rheographically, a good clinical response with improvement of peripheral
circulation was achieved.
PMID- 9643145
TI - [Bioelectrostimulation in the rehabilitation of patients with gunshot wounds of
the peripheral nervous system (a clinico-immunological study)].
AB - Immune homeostasis was studied in 35 patients with gunshot injuries of the
peripheral nerves in the process of rehabilitation using bioelectrostimulation of
the muscles impaired. Parameters of cellular and humoral immunity were
determined. Bioelectrostimulation resulted in the regression of preexisting
motor, sensitive, vegetovascular and trophic disorders. Cellular and humoral
immunity improved: the number of T-lymphocytes, T-helpers, T-suppressors
increased, the immunoregulatory index normalized, levels of B-lymphocytes,
immunoglobulins G, circulating immune complexes reduced. Thus,
bioelectrostimulation in patients with gunshot injuries of the peripheral nerves
corrects the disturbed homeostasis and promotes recovery of the functions lost.
PMID- 9643147
TI - [A comparative evaluation of the effect of different types of sapropel on dynamic
liver function in intact rats and in the modelling of toxic hepatitis].
AB - A course of silicic sapropel applications compared to calcareous sapropel induced
a reversible fall of total lipid concentration in blood serum of intact rats.
Sapropels of different kinds and of the same kind but obtained from different
depths of the same deposit varied by their ability to correct hepatic function in
rats with toxic hepatitis. The highest benefit was registered in application of
carbonate sapropels taken from the depth of 1.5-2.5 m.
PMID- 9643146
TI - [The effect of the combined action of applications of sapropel and of a
nonuniform permanent magnetic field on the dynamics of the recovery processes in
damage to the liver parenchyma (experimental research)].
AB - Effectiveness of applications of saprol and nonuniform constant magnetic field
(NUCMF) used alone and in combination was studied on the model of experimental
toxic rat hepatitis. NUCMF had no advantages over saprol in correction of hepatic
tissue function. However, combination of these two modalities was more effective
than each of them. Possible mechanisms of such effect are discussed.
PMID- 9643148
TI - [The information value of the cardiorespiratory system indices of rats in
assessing the dependence between heat inflow from peloid application and the
body's reaction].
AB - Informative value of cardiorespiratory parameters of rats in respect to dose
effect effectiveness was studied in relation to thermal action of therapeutic
peloid. Systolic blood pressure and respiratory rate are highly informative
whereas heart rate is not responsive to thermal effect of the peloid. Possible
explanation of the above facts are discussed.
PMID- 9643149
TI - [The marketing characteristics of sanatorium-health resort institutions].
PMID- 9643150
TI - [The organization of a medical rehabilitation service].
PMID- 9643151
TI - [The problems of radon therapy: its benefits and risks].
PMID- 9643152
TI - Human resources development for the prevention of blindness in Anglophone West
Africa.
AB - As recent as 1986, acute shortage of qualified manpower was one of the major
difficulties in the prevention of blindness in Africa. Following the WHO sub
regional workshop on Manpower development for Prevention of Blindness, the West
African Health Community in collaboration with the National Prevention of
Blindness programmes in Anglophone West Africa made concerted efforts at
developing appropriate manpower at all levels of eye care. Eight categories of
eye care workers were identified and personnel to population ratios adopted for
each. Curriculum was developed and training begun for two new cadres-Primary Eye
care Trainers and Diplomate Ophthalmologist. These are expected to boost the
training of Integrated Eye Care workers for primary eye care and increase
surgical services, especially cataract surgery rates, at secondary eye care level
respectively. There are constraints and difficulties but the support provided by
two non-government organisations (Sight Savers International and Christoffel
Blindenmission) had been helpful in overcoming some of these. Significant
progress has been made in the last decade in developing the required manpower but
large deficits still remain. The political will, commitment and co-operation of
all stakeholders would be required to achieve the desired targets for the next
decade.
PMID- 9643153
TI - [Treatment of early T1 small T2N breast cancers. Our experience at the Yaounde
General Hospital. 21 cases].
AB - From February 1989 through February 1993, a group of 23 patients suffering from
T1 mammary carcinoma small T2 N-MO was treated in the radiotherapy department of
the Yaounde General Hospital, according to a simplified procedure. A first
conservative surgery of tumorectomy type (3 cases) and quandrantectomy type (4
cases) was carried out, followed by a postoperative irradiation. In 14 cases, a
Patey type radical surgery preceded a local/regional radiotherapy. The general
treatment was made up of only a hormonotherapy without chemotherapy. After a 4
year decline, there were 5 cases--i.e. 23.8%--of ganglionic and/or metastatic
relapse. In the light of research data, we are analysing the reasons for these
unexpected therapeutic failures in this group of tumor considered as favorable
prognosis. We raised the problem of the inability of the prognosis factors,
presently defined by means of histological and biological factors, to detect all
the especially aggressive cancers. We carried out a general review of the new
factors defined essentially from molecular and genic bases. We offered an
approximative solution which makes it possible to by-pass the technological
difficulties in having access to the new factors.
PMID- 9643154
TI - Febrile illness a major cause of profound childhood deafness in Nigeria.
AB - A prospective study of 63 children with profound deafness seen personally at the
E.N.T. Clinic, University of Nigeria Teaching Hospital, Enugu between January,
1984 and October, 1987 is the subject of this paper. There were 35 males and 28
females. Thirty-six (57.1%) were in the age group, 0-3 years, 17 (27%) in the age
group 4-6 years, 7 (11.1%) in the age group 7-10, and 3 (4.8%) over 11 years.
Febrile illness 41.3% was the most common cause followed by unknown with about
20.6%. The various causes were compared with causes from other parts of the
world. The possible causes of the febrile illness with special emphasis on the
role of viral infections and malaria are highlighted. Mention is made of possible
preventive measures.
PMID- 9643155
TI - Screening of potential semen donors for sexual transmitted diseases.
AB - BACKGROUND AND OBJECTIVES: The risk of infection with sexually transmitted
diseases (STDs) is of great concern to couples undergoing therapeutic donor
insemination. GOAL OF STUDY: We sought to determine the prevalence of STDs in
potential semen donors and assess the rate of acquisition of new infection during
the follow-up period. STUDY DESIGN: 29 potential semen donors were screened for
common STDs. RESULTS: The study population had a prevalence of the following
STDs: 27.5% ureaplasma, 13.8% mycoplasma, 6.9% cytomegalovirus 6.9% group B
streptococcus, and 3.4% human papillomavirus infection. No participant tested
positive for gonoccoccal or HIV infection. Over all, evidence of STD was present
in 10 of 29 (34.5%) prospective donors. A follow-up infection rate of 22.2% (6 of
27 enrolled donors) was found and 3 (11.1%) of these were excluded from semen
donation. CONCLUSION: A high prevalence of sexually transmissible infections is
present in potential semen donors. New infections are also common during the
follow-up period.
PMID- 9643156
TI - Trends in cervical cancer screening in Ibadan, Nigeria: a four-year review.
AB - A four year retrospective review of cervical cytology services at the University
College Hospital between 1992 and 1995 was carried out with a view to evaluating
the trends in attendance, cost, sociodemographic characteristics and pattern of
abnormal smears. The results were compared to those of an initial 4-year period
(1988-1991) when the service was initiated. Fifty-three percent (53.8%) of 1,127
smears taken during the period were routine smears. Majority (45.8%) of the
smears were non-specific inflammatory changes while 26.8% were negative. Cervical
intraepithelial Neoplasia (CIN) was diagnosed in 11.8% while 5 patients (0.44%)
had neoplastic changes. The mean age were 39.8 (+/- 9.5), 40 (+/- 9), 52 (+/- 6)
years for the entire study population, patients with CIN and patients with
neoplastic changes respectively. There is a general decline in the number of
smears taken while the cost of the procedure increased over the study period. In
10.5% there are inadequate documentation and missing results. In our country
where cervical cancer is the commonest female malignancy and leading cause of
death among women, there is an urgent need to reverse this unfavourable trend,
through use of public education, inducement, staff motivation and training in
addition to computerisation of data.
PMID- 9643157
TI - Utilisation differentials in a rural Nigerian health centre.
AB - The Ala-Idowa health centre was established in 1980 to serve the two contiguous
communities of Ala and Idowa with population of 3960 and 6580 respectively.
Situated reasonably between the two communities, there is adequate physical
accessibility to the health centre from both sides. The population structure of
the combined community was determined through a household survey involving 125
households selected systematically from the total of 2500 households. A
comparison is presented between this structure and that of the population of
attendees at the outpatient department of the Ala/Idowa health centre as recorded
in the outpatient register with a view to discerning differentials in utilisation
among different age groups. The data showed that those under the age of 15 years
made more use of the health centre services than any other age group. Also, of
the total of 958 patients for whom a diagnosis was recorded, 565 (56%) presented
with an infection or infestation alone while another 4% presented with an
infection together with another condition. Malaria accounted for 358 (63.4%) of
all reported cases of infection/infestation. It is hoped that the findings of
this study can be used to further target health centre services at the
appropriate groups within the community as well as directed to those conditions,
particularly communicable and preventable, that continue to exert great morbidity
on the populations of developing communities.
PMID- 9643158
TI - Seroprevalence of hepatitis markers; HAV, HBV, HCV and HEV amongst primary school
children in Freetown, Sierra Leone.
AB - The prevalence of hepatitis markers (Hepatitis A, B, C and E) in primary school
children in Freetown, Sierra Leone was investigated in a government school,
representative of the urban middle class. The children were aged between 6-12
years old. A sub-sample (n = 120) of the 450 pupils were invited to participate.
Of the 66 volunteers (mean 8.32 years) 12 were positive for HBsAg (males 9,
females 3) and 11 were confirmed. Six of these were HBeAg positive, anti-HBe
negative, (male 5, female 1). Whilst 6 were HBeAg negative, anti-HBe positive
(male 4, female 2). HBcAb was present in 47 children (71%). Hepatitis A, C and E
antibodies were detected in 64 (97%), 1 (2%) and 5 (8%) of children respectively.
PMID- 9643159
TI - Evaluating the laboratory techniques used in the diagnosis of sputum-producing
patients suspected of Mycobacterium infection.
AB - Because of the susceptibility of HIV-infected persons to Mycobacterial
infections, more sensitive diagnostic technique are being employed to detect
Mycobacterium spp from clinical specimens. This study was therefore carried out
to evaluate the sensitivity of methods used for the diagnosis of mycobacterial
infections among sputum producing patients. Sputum samples from 160 patients were
examined for Mycobacterium spp using direct smear microscopy, concentrated smear
microscopy, and cultural method. The cultural technique detected the highest
number of positives, 62 (38.8%), followed by concentrated smear technique,, 41
(25.6%) while direct smear technique detected only 24 (15.0%). The results show
that cultural technique should be employed for the diagnosis of Mycobacterium in
order to avoid false negative results. However, concentrated smear technique
should always be carried out, so that treatment could commence immediately in
obviously positive cases.
PMID- 9643160
TI - The effect of lacidipine on patients with mild to moderate hypertension and the
effect of a combination of lacidipine and hydrochlorothiazide in the treatment of
hypertension uncontrolled after four weeks of lacidipine treatment: an open
study.
AB - In the treatment of hypertension, some patients may go off control while still on
the drugs. This occurs especially with sympathetic inhibitors and vasodilators.
Lacidipine, a new calcium antagonist acts principally by vasodilatation. After a
wash out period, patients with mild to moderate hypertension received 4 mg of
Lacidipine for two weeks. After evaluation at two weeks, those uncontrolled
received 6 mg of Lacidipine, while those controlled continued with 4 mg of
Lacidipine for another two weeks. By the next evaluation, while patients
continued whatever doses they were on, any one who had gone off control had 25 mg
of Hydrochlorothiazide added. They were evaluated finally after another two
weeks. It was found in this study that 91.3% (21/23) were controlled by the end
with only Lacidipine either in 4 mg or 6 mg doses. Another 8.7% (2/23) initially
controlled on Lacidipine went off control while still on the drug, and were
eventually controlled by adding Hydrochlorothiazide. Some transient side effects
not warranting discontinuation were encountered. It is concluded that Lacidipine
is effective as monotherapy in mildly to moderately hypertensive Nigerian
Africans; with good tolerance and safety profile. Where transient control is
encountered, addition of a diuretic could be beneficial.
PMID- 9643161
TI - Lysis of left ventricular thrombus with urokinase in a patient with alcohol heart
disease.
AB - A dilated cardiomyopathy patient whose congestive cardiac failure was made
refractory to treatment by a left ventricular thrombus is reported.
Thrombolectomy is usually the preferred therapeutic approach over anticoagulation
and thrombolysis, as the latter approaches are said to carry the risk of stroke
and haermorrhage. Facilities for thrombolectomy may not be available or
affordable in our setting, and in some patients not practicable. Where 2-D echo
facilities are available to indicate complete lysis, thrombolysis may be a way
out.
PMID- 9643162
TI - Atrial myxoma--a case report and review of the literature.
AB - Myxomas are the most common primary cardiac tumours. They are usually benign and
have variable presentation. Although rare, atrial myxomas are the most important
cardiac tumours to diagnose, as they have an excellent prognosis following
surgical excision. We report a 56 year old man who presented with features of
both right and left heart failure. Ausculation of the heart revealed an apical
mid diastolic murmur. Two-dimensional colour flow Doppler echocardiography
revealed a pedunculated left atrial myxoma that prolapsed into the mitral valve
orifice in diastole producing functional mitral valve stenosis. The patient
underwent a successful surgical excision of the tumour. The diagnosis and
management of atrial myxomas is reviewed.
PMID- 9643163
TI - An unusual chest impalement.
AB - We present the case of a 49-year old farmer, a combatant in communal clash over a
piece of farmland on the Jos Plateau, who was impaled on his chest by a 13.5 cm
long metal arrow, 56 hours prior to presentation. The arrow hit him tangentially
on the left side of the chest and disappeared completely into his chest
traversing the chest wall and lacerating the superior lingula segment of the lung
but the tip of the arrow was only about 1.5 cm short of the pericardium. We are
not aware of any report in literature on a patient in the West African sub-region
who sustained and survived such serious chest impalement by a rigid object for
more than two days before hospitalisation. Sustained public education and
enforced legislature against the use of such lethal weapons will go a long way in
preventing serious injuries of this nature.
PMID- 9643164
TI - Correlation of mATPase, parvalbumin, and cytochrome c oxidase in rat skeletal
muscle fibres.
AB - Muscle fibre typing is conventionally performed on unfixed frozen sections.
Within the particular classes of fibre types mATPase correlates well with the
type of myosin heavy chain (MHC). However, investigation of other properties,
e.g., parvalbumin (PV) level, cannot be determined on unfixed frozen sections.
Determination of PV, which correlates with the relaxation time, is performed
immunohistochemically on fixed tissue. By that method a comparison of mATPase
activity and the amount of PV within the same muscle fibre is difficult. The
present method, combining histochemistry of mATPase and cytochrome c oxidase with
parvalbumin immunohistochemistry on consecutive sections, allows the distinction
of six fibre types: I, IB, IIA, IIB, IIAB, IIX, and a C fibre population without
division into IC and IIC fibres. The advantages and disadvantages of the present
method are discussed.
PMID- 9643165
TI - Composition of lipids from the glands of the external ear canal of the adult
chicken.
AB - Six classes of neutral lipids, i.e. triacylglycerol (TG), free fatty acids (FFA),
monoester waxes (MW), free- and esterified sterols (FST and SE), and squalene
(SQ) were identified by thin layer chromatography of the lipid materials
extracted separately from the secretion as well as from the isolated whole glands
present in the skin of the floor of the external ear canal of the domestic fowl.
Secretory lipids contained considerable proportions of MW fractions (17.03%), TG
(22.23%), and SQ (14.66%), while TG was the major component (41.10%) in the
lipids from the isolated glands. Polar lipids, which comprised about 16-20% of
total glandular lipids, were shown to be composed primarily of sphingomyelin.
PMID- 9643166
TI - Melatonin action on thyroid activity in the soft-shelled turtle, Lissemys
punctata punctata.
AB - Adult female turtles (Lissemys punctata punctata) were treated with pineal
indoleamine melatonin (100 micrograms/100 g) or the antithyroid agent,
methylthiouracil (100 micrograms/100 g) or melatonin together with
methylthiouracil (100 micrograms of each drug/100 g) for 12 days. Melatonin alone
inhibited thyroid activity as evidenced by reduction in the gland weight,
follicular epithelial cell height, thyroid peroxidase, and plasma thyroxine
levels. Methylthiouracil caused hyperplasia of the gland, although it inhibited
thyroid activity and reduced thyroid peroxidase and plasma thyroxine levels.
Melatonin together with methylthiouracil produced changes similar to those
obtained with melatonin alone. The results indicate that melatonin probably
exerts inhibitory effects influences on both thyrotropin release from the
pituitary and the activity of the thyroid itself in turtles.
PMID- 9643167
TI - Ultrastructural and cytochemical identification of peroxisomes in Balantidium
coli, Ciliophora.
AB - Peroxisomes of the trophozoites of Balantidium coli isolated from pig intestine
content were investigated, using ultrastructural and cytochemical techniques. The
peroxisomes of B. coli trophozoites from pigs with subclinical balantidiasis are
less then 0.8 mm in diameter whereas those from pigs with acute balantidiasis are
greater than 0.8 micron in diameter. In all the trophozoites peroxisomes are
round, oval or dumb-bell shaped. Catalase as an indicative enzyme was detected by
cytochemical techniques in B. coli peroxisomes.
PMID- 9643168
TI - A comparison of nucleic acid content in Balantidium coli trophozoites from
different isolates.
AB - Cytophotometric assays were performed on Balantidium coli trophozoites isolated
from 30 pigs affected by acute balantidiasis (Group I) and from 30 pigs with
symptom-free balantidiasis (Group II). Trophozoites from cultures obtained from
Group I and II pig isolates were assayed for comparison. Comparative
cytophotometric studies on nucleic acids of B. coli trophozoites isolated from
acute and symptomless balantidiasis-affected pigs as well as from in vitro
cultured trophozoites showed differences which could have resulted from
differences between populations in the trophozoans under investigation.
PMID- 9643169
TI - The "comet" assay for detection of potential genotoxicity of polluted water.
AB - The aim of this study was to determine the potential genotoxic activity of
polluted water samples taken from wastewater from selected industrial plants in
Krakow: 1. the Thermal-electric Power Station 2. the Institute of Metal Cutting.
The recently developed single cell gel assay (SCG or comet assay), which is a
quick and simple technique for the evaluation of DNA damage and repair in
individual cells, was used. The assay was carried out on human hepatoma cells
(Hep G2) as target cells. A greater number of cells with comets was observed in
those treated in vitro with the polluted water samples (70%-88%) than in those in
the control (22%, 33%). These preliminary results indicate that comet assay can
have an application in biomonitoring studies for determining the potential
genotoxicity of water pollutants.
PMID- 9643170
TI - Haematological changes in buprenorphine-treated mice.
AB - Studies were carried out in adult male Swiss mice to determine whether different
haematological parameters like total counts of red and white blood cells,
differential counts of white blood cells, haematocrit value and blood haemoglobin
level were affected by the synthetic opioid analgesic, buprenorphine, which has
currently been known to be abused in several countries by the heroin addicts as a
cheap substitute for heroin. The mice were daily given an intraperitoneal
injection of buprenorphine (300 micrograms/kg) for 60 consecutive days. A severe
leucopenia accompanied by decreases in lymphocyte and monocyte counts, an
increase in neutrophil count, a decrease in haematocrit value, a rossette-like
adherence of red blood cells to a few neutrophils and platelet satellitism were
observed at the advanced stages of treatment. The abnormalities, however,
reverted to normal within 45 days following withdrawal of the drug. The necessity
of periodic monitoring of the blood picture in human abusers of the drug is
suggested.
PMID- 9643171
TI - Prognosis of conventional root canal treatment reconsidered.
AB - In endodontic literature, the so-called success rate of conventional root canal
treatment is reported to range between 70% and 95%. This has been calculated as
the percentage of successfully treated teeth of all teeth followed up or included
in the clinical trial. This approach, however, does not allow for valid
assertions on the prognosis of root canal treatment as the individual observation
times are not considered. This article discusses some methodological and
statistical aspects of how to design a prognostic study which focuses on the
outcome of endodontic therapy and of how to analyse the data appropriately.
Methodologically, the response variable should preferably be the individual time
required for the occurrence of an event, e.g., success or failure of endodontic
therapy, which should clearly be defined on the basis of widely accepted criteria
in endodontology. Event times can appropriately be analysed by the Kaplan-Meier
method, which estimates the probability that the event will not occur within a
fixed time. This probability, together with the approximate 95% confidence
interval (CI), permits an evaluation of the prognosis of a particular treatment.
Two data sets were re-analysed to clarify the rationale behind the analysis of
event times. Accordingly, the probability that an endodontically induced lesion
will completely heal, e.g., within the first 3 years after root canal therapy
ranges between 0.87 (CI: 0.74-1.00) and 0.89 (CI: 0.80-0.98). In this situation,
the simple calculation of success rates would overestimate the chance of complete
periapical healing within the first years after therapy but underestimate it over
longer observation periods. Another example was used to analyse the time to
occurrence of periapical pathosis associated with root canal treated teeth not
diseased periapically. In this case the chance of recording a successful
endodontic treatment is initially underestimated by the percentage of successful
cases of all teeth integrated in the study but is markedly overestimated for
longer observation periods. Potential risk factors affecting the outcome of the
endodontic therapy and thereby the event times can adequately be determined by
applying the Cox's or Aalen's regression model.
PMID- 9643172
TI - Cutting pattern of nickel-titanium files using two preparation techniques.
AB - The aim of this study was to examine the cutting patterns of recently introduced
nickel-titanium endodontic files and compare them with similarly shaped stainless
steel files using both balanced-force and stepback techniques. Simulated canals
were constructed in resin blocks with 40 degrees curvature. Fifty blocks were
prepared by a balanced-force technique: 25 with Nitiflex (Maillefer) and 25 with
Flexofiles (Maillefer) to master apical file size 40. Fifty blocks were prepared
by a stepback technique: 25 with Nitiflex and 25 with Flexofiles to a master
apical file size 30. Composite prints were made of pre- and post-instrumentation
canals using a computerized imaging system. The amount of material removed from
the inner and outer canal curvatures was measured at eight levels in the apical
11 mm of the canal. The results were analysed by Kruskal-Wallis ANOVA. Using the
balanced-force technique, Nitiflex files removed less material on the outer curve
apically and less on the inner curve mid-canal (P < 0.05), while Flexofiles
caused more apical transportation. In the stepback technique, the Nitiflex files
removed more material from the outer curve apically (P < 0.05); the Flexofiles
removed more material along the entire inner curve (P < 0.05), and maintained
canal curvature better than Nitiflex files. It appeared preferable to use
Nitiflex files in a balanced-force technique, and Flexofiles in a filing
technique as stainless steel files can be precurved.
PMID- 9643173
TI - An in vitro evaluation of canal preparation using Profile .04 and .06 taper
instruments.
AB - A model system involving a double radiographic exposure technique was developed
in order to evaluate maintenance of the original canal path of curved root
canals. The mesiobuccal roots of 30 maxillary molars were prepared using one of
three techniques (n = 10 in each group). One group was instrumented using rotary
Profile .04 tapers and a second group was prepared using orifice openers, rotary
Profile .04 and .06 tapers. The final group was prepared using Profile hand files
.02 taper and Gates-Glidden drills. Canal transportation was evaluated in the
apical, middle and coronal regions from the double-exposed radiographs. Canal
shape was determined by the ease with which a D11T spreader passed to within 1 mm
of the working length. Time of instrumentation was also recorded. The results
showed no significant difference between the techniques in canal transportation
in the apical, middle or coronal regions (P > 0.05). It was significantly easier
to place the D11T spreader in the .06 taper group (P < 0.05). Canal preparation
was significantly quicker in the .04 taper group (P < 0.05). In conclusion, the
use of .06 taper files improved canal shape and did not increase transportation.
The additional file changes, however, increased the instrumentation time.
PMID- 9643174
TI - In vitro evaluation of the cytotoxicity of a bleaching agent.
AB - Cell cultures of L929 and BHK21/C13 cells were used to evaluate the toxicity of a
newly introduced bleaching agent (Colgate Platinum) compared to hydrogen
peroxide, an established bleaching agent. The cell reaction was determined by a
quantitative technique at 24 h and 72 h. Both bleaching materials had a dose
dependent effect on cell viability. Concentrations of hydrogen peroxide causing a
50% decrease in cell number (50% inhibition dose-ID50) were calculated as
0.00034% after 24 h and 0.00001% after 72 h in L929 cells. The ID50 of hydrogen
peroxide was found to be 0.00016% after 24 h and 0.00007% after 72 h in BHK21/C13
cells. The ID50 of Colgate Platinum was 0.00074% after 24 h and 0.00045% after 72
h in L929 cells and 0.00055% after 24 h and 0.00024% after 72 h in BHK21/C13
cells. The results showed that, in vitro, both bleaching agents were cytotoxic to
fibroblasts and the new bleaching agent was less toxic than hydrogen peroxide.
PMID- 9643175
TI - Effect of argon laser irradiation on instrumented root canal walls.
AB - The objective of the study was to examine whether argon laser has a property to
remove debris and smear layer from root canal walls. Twelve endodontically
treated human maxillary molar teeth with three root canals were divided into two
groups of six teeth. The first group was left unlased as a control; in the second
group the root canals were irradiated by argon laser (laser parameters were set
at 1 W and pulse duration and pulse frequency fixed at 0.05 s and 5 Hz). After
the usual root canal preparation and lasing had been carried out, the teeth were
decoronated, bisected longitudinally, observed with a scanning electron
microscope and evaluated as to how clean the surfaces of root canal walls were.
In most cases control teeth presented surfaces with debris covering the root
canals, obscuring the dentinal tubules. Only 1 of 18 specimens was free of
debris. In the lased group, root canal surfaces free of debris and vaporized
pulpal tissue remnants were observed in 13 of 18 specimens. The results showed
significant statistical differences between the control group and the lased
groups (P < 0.001). These results suggested that argon laser irradiation has an
efficient cleaning effect on instrumented root canal surfaces.
PMID- 9643176
TI - Sequelae of trauma to primary maxillary incisors. I. Complications in the primary
dentition.
AB - Two hundred and eighty-seven children with a total of 545 traumatized primary
upper incisors were followed using standardized procedures until the age of 10.
Extraction was the only treatment offered when intervention was necessary. The
immediate as well as the long-term consequences of trauma were studied on the
basis of this material. Consequences in the primary dentition comprised: color
changes (53%), pulp necrosis (25%), pulp canal obliteration (36%), gingival
retraction (6%), permanent displacement after luxation (5-22%), pathological root
resorption (1-10%) as well as disturbances in physiological root resorption (4%)
and, lastly, premature tooth loss (46%). In a multivariate analysis of the
development of pulp necross in primary teeth after trauma, the following decisive
factors were found: age of the patient at the time of injury, degree of
displacement of the tooth as well as the degree of loosening and presence of
crown fracture. The factors found to influence development of pulp canal
obliteration were: displacement of the tooth at time of injury as well as
detectable physiologic root resorption at time of trauma. The presence of crown
fracture seemed to decrease the risk of obliteration. The need for scientifically
based treatment strategies for managing and reducting complications after trauma
in the primary dentition is stressed.
PMID- 9643177
TI - Forces transmitted through a laminated mouthguard material with a Sorbothane
insert.
AB - Sorbothane is a visco-elastic polyurethane that has been used in sports and
orthopaedic applications because of its shock-absorbing properties. The aim of
this laboratory study was to evaluate the effect of an intermediate layer of
Sorbothane on the peak force transmitted through two thermoplastic ethylene vinyl
acetate (EVA) sheets as used in the construction of a custom-made sports
mouthguard. The EVA sheets were tested at room temperature after thermal
lamination under pressure, either without (control) or with a Sorbothane
intermediate layer of 1.1 or 2.65 mm thickness. A piezo-electric transducer was
used to measure the peak force transmitted through each sample from a free
falling steel ram. The peak force recorded was significantly less for laminated
EVA samples with a Sorbothane intermediate layer than for controls of comparable
thickness. We conclude that a Sorbothane intermediate layer between heat-cured
laminated EVA sheets, as used in the fabrication of a custom-made sports
mouthguard, may dissipate significantly the force of impact resulting from a blow
to the teeth and jaws.
PMID- 9643178
TI - Complicated crown fracture of an unerupted permanent tooth--a case report.
AB - Trauma to primary teeth may result in direct damage to underlying developing
permanent teeth because of the close relationship that exists between the apices
of the primary teeth and their permanent successors. Injuries to developing teeth
have been classified into ten different categories, using a classification that
is largely based on developmental alterations to the permanent teeth. However,
this classification does not include other types of trauma that may occur to
developing teeth, such as crown fractures. Although apparently rare, such
injuries can occur by direct contact of the impacting object with a developing
tooth, as illustrated by the following case report.
PMID- 9643179
TI - Splint therapy for skeletal Class III malocclusion in the primary dentition.
AB - An orthopedic appliance for the correction of skeletal Class III malocclusion in
the primary dentition is described. The appliance consists of two resin splints
with hooks for Class III elastic intraoral traction. Construction features and
biomechanical aspects of the device are described along with the clinical
evaluation of treatment effects in two case reports.
PMID- 9643180
TI - Oral rehabilitation in dentinogenesis imperfecta with overdentures: case report.
AB - A seventeen-year-old girl demonstrating severely worn permanent dentition and
multiple retained root stumps with dentinogenesis imperfecta is presented.
Overdentures were made to preserve bone height, re-establish the lost vertical
dimension of occlusion, to provide acceptable esthetics, and to establish an
efficient masticatory system.
PMID- 9643181
TI - A conservative approach to the pulpotomy in primary teeth.
AB - This study evaluates the importance of preserving the dentinal roof of the pulp
chamber, when the pulpotomy technique is performed, thus obtaining an important
reinforcement of the tooth by employing a very simple technique. Therefore, the
current vertical fracture of the primary molars is avoided even though a steel
crown is not adapted.
PMID- 9643182
TI - Class III cavity preparation in primary anterior teeth: in vitro retention
comparison of conventional and modified forms.
AB - Management of mild to moderate caries in primary anterior teeth is still a
problem. Presently, class III composite restorations in primary teeth have
inadequate retention. The purpose of this in vitro study was to analyze the
influence of the design of modified class III cavity preparation on the retention
of the restoration when compared to that of the conventional class III
preparation. Thirty extracted human primary maxillary central incisors were
divided into two groups of 15 teeth each. In one group, the conventional
(triangular) class III design was prepared. The second group, the modified class
III design, was prepared by adding to the conventional form, 0.5 mm. labial
reduction on the labial tooth surface. The dentinal bonding agent, Amalgambond,
was applied to 30 teeth according to instructions of manufacturer. The composite
resin, Herculite XRV, was inserted into each preparation. All samples were
mounted in plastic molds and thermocycled. The samples were tested with Instron
testing machine until restoration failure. Results showed that the mean failure
load of modified class III restoration group (92.19 +/- 13.6 N) was significantly
higher from that of conventional class III preparation group (45.61 +/- 9.8 N) as
tested by Student's independent t-test (P < 0.001).
PMID- 9643183
TI - Chamfered margin effects on occlusal microleakage of primary molar Class I
composite resin restorations in vitro.
AB - Recent clinical studies have suggested that composite resin may be an effective
restorative material for the restoration of Class I preparation in primary
molars. The primary objective of this study was to assess the effects in vitro of
a chamfered margin on occlusal microleakage of class I posterior composite resin
restorations in primary molars. Two cavity preparations (conventional and
modified) were compared by using forty extracted primary molars. The modified
class I preparation as described in this study showed no occlusal microleakage
and recommended to be further studied clinically. The difference between these
two groups was analyzed by using the Fisher Exact Probability Test and was
statistically significant.
PMID- 9643184
TI - Loss of space and dental arch length after the loss of the lower first primary
molar: a longitudinal study.
AB - The premature loss of primary teeth may harm the normal occlusal development,
although there are debates relating to the necessity of using space maintainer
appliances. The aim of the study is to evaluate the changes in the dental arch
perimeter and the space reduction after the premature loss of the lower first
primary molar in the mixed dentition stage. The sample consists of 4 lower arch
plaster models of 31 patients, within the period of pre-extraction, 6, 12 and 18
months after the lower first primary molar extraction. A reduction of space was
of noted with the cuspid dislocation and the permanent incisors moving toward the
space of the extraction site. It was concluded that the lower first molar primary
premature loss, during the mixed dentition, implicates an immediate placement of
a space maintainer.
PMID- 9643185
TI - Estimated skin exposure as an indicator for comparing radiovisiography (RVG)
versus conventional Ektaspeed Plus dental radiography.
AB - An Everest 3000 Radiovisiography (RVG) Video system (Trophy USA Inc.,
Fredericksburg, VA 22402) was compared with conventional radiography using
Ektaspeed Plus film (Eastman Kodak Co., Rochester, NY 14650). Previous studies of
the RVG system with a special computer controlled x-ray timer (Trophy USA, Inc.)
claimed a significant reduction in radiation. Trophy has also claimed that the
RVG system can provide diagnostic quality images utilizing existing conventional
x-ray generators. This study used a conventional timer and generator. Since it
would be logical to assume that many practitioners would use the equipment "in
place" rather than invest in new, unfamiliar equipment. Estimated Skin Exposure
(air) was used as the primary criteria for comparative purposes. Exposure has
been defined as "a measure of radiation quantity, the capacity of ionize air. The
roentgen (R), is the traditional unit of radiation exposure measured in air"; The
results indicate that the RVG system when combined with a standard conventional
timer actually generated greater radiation exposure than does standard, routine
radiography.
PMID- 9643186
TI - Orthodontic treatment priority: a comparison of two indices.
AB - Approval for state sponsored funding of orthodontic treatment is often decided
using an index of malocclusion. The purpose of this study was to determine
whether two indices used for prioritizing patients would identify different
groups of individuals qualifying for orthodontic treatment funding approval. In
addition, the characteristics of patients approved using different indices were
compared. The records of 40 patients previously submitted for state medicaid
funding approval were evaluated by three study examiners using two orthodontic
treatment priority indices, the Salzmann Handicapping Malocclusion Assessment
(Salzmann) and the Index of Orthodontic Treatment Need (IOTN). Comparisons were
made between state medicaid and study examiner Salzmann scores, rankings, and
funding decisions, and between study examiner Salzmann rankings, IOTN rankings,
and funding decisions. Correlation and rank correlation coefficients between the
state and study examiners' Salzman scores were high (r = 0.74; p < 0.001, and R =
0.77; p < 0.001). Rank correlation analysis of the study examiners' Salzmann and
IOTN values demonstrated a weaker relationship (R = 0.40; p < 0.02). Agreement on
funding decisions, evaluated by the Kappa statistic, was greater between the two
Salzmann evaluations (K = 0.57) than between the study examiners' Salzmann and
IOTN evaluations (K = 0.14). As expected, depending on the method used to
determine orthodontic treatment funding priority, different patients were likely
to be identified for treatment approval. The characteristics of patients whose
treatment was approved was closely related to the criteria defined by the method
employed.
PMID- 9643187
TI - Profile of non-nutritive sucking habits in relation to nursing behavior in pre
school children.
AB - Although a number of investigators have studied the prevalence and etiology of
non-nutritive sucking habits in children, no consensus exists among dental and
medical experts in respect to the contributing factors and preventing behaviors.
Furthermore, changes in the rearing practices of children make management of such
habits even more complicated. The purpose of the present study was to investigate
finger and pacifier sucking habits among pre-school children, and its possible
relationship to nursing behavior. Parental attitudes towards sucking habits were
also registered. Questionnaires were sent to parents of 600 children, three to
five years old, following an oral examination in a private office. Children
attended kindergartens that were randomly selected from the area of Athens,
Greece. Questions regarding the nursing patterns-breast or bottle feeding
characteristics of finger and pacifier sucking habits, parental attitudes towards
sucking habits, as well as recommendations of the pediatricians were included.
Three hundred and sixteen questionnaires were returned by parents. Results
indicated that pre-school children discontinued a pacifier sucking habit earlier
compared to a finger habit. Pacifiers showed a preventive effect against finger
sucking, since only 2% of the sample examined practiced both habits. Breast
feeding was not clearly associated with sucking habits; however, long bottle
feeding periods were related with decreased finger sucking and high figures of
pacifier sucking. The majority of pediatricians were not in favor of an
intervention in breaking a finger sucking habit of the child.
PMID- 9643188
TI - Inhaler medicament effects on saliva and plaque pH in asthmatic children.
AB - The purpose of the present study was to investigate the effect on saliva and
plaque pH of beta 2 agonist (salbutamol 400 mcg) and inhaler corticosteroid
(fluticasonepropionate 250 mcg). The interproximal plaque pH responses to these
medicaments and examine the effect of chewing gum after the usage of these
inhalers. Thirty children of both sexes, from six to fourteen years old,
participated in the study. The pH microelectrode was used in the study. The
interdental sites chosen were those between the premolars in the 4 quadrants. The
pH measurements were made baseline and 1, 5, 10, 20, 30 minutes after the use of
medicaments as inhaler and also saliva was stimulated by sugar free chewing gum
(Vivident). Data analyses were conducted using a statistical package through the
University's computing center. The resulting pH values decreased in all four
plaque sites and saliva during 30 minutes after inhaler drugs. After rinsing with
water, the pH values also decreased (p < 0.001). Decreasing pH increased with
chewing gum (p < 0.001). The hypothesis is that a decrease in pH in medicated
asthmatics could be caused by inhaler drugs. Conclusive evidence for the relative
role of the disease and the drug in saliva secretion and composition seems to
require a longitudinal study on asthmatics before and after the onset of drug
administration. We suggest that children with bronchial asthma treated with
inhaler drugs should receive special preventive attention.
PMID- 9643189
TI - Neutrophil chemotaxis in Down syndrome and normal children to Actinobacillus
actinomycetemcomitans.
AB - During the last decade a lot of attention has been diverted to the study of
Actinobacillus actinomycetemcomitans (Aa) as the principal micro-organism in the
pathogenesis of periodontal disease. Because of the defective body defenses,
there is an increased likelihood of periodontal disease among the Down syndrome
patients. An attempt has been made herein to correlate the relationship between
the gingival and periodontal health status to the isolation of Aa from the
subgingival plaque in Down syndrome cases and to compare it to the neutrophil
chemotactic activity to the normal subjects. Strong association between the
occurrence of Aa as well as significant differences between the healthy and Down
syndrome subjects in neutrophil defense activity were observed.
PMID- 9643190
TI - Dermatoglyphic findings in dental caries: a preliminary report.
AB - The dermatoglyphs of caries-free students and the students with dental caries in
10 or more teeth were compared. The caries-free students had an increased
frequency of ulnar loops on all fingers. In contrast, the students with dental
caries had an increased frequency of whorls on all fingers.
PMID- 9643191
TI - "9-year-molars" aberrantly developing and erupting: report of cases.
AB - This paper describes delayed development and eruption of the first permanent
molars, in most cases only in the upper jaw. The development and eruption of the
teeth are chronologically between that of the first and second molars. The
anatomy of the aberrant teeth is closest to that of the second molars. The
aberrant teeth are often laying at a distance during development from the second
primary molars. The clinical implications of the aberrancy are few, because the
teeth will normally migrate into close contact with the tooth mesial to them,
however, often into a crossbite. Most often the teeth are mistaken to be a first
molar with some eruption disturbance and therefore referred for surgical or
orthodontic treatment. However, such interception should be avoided because at
least in the present cases all teeth are observed to erupt by themselves.
PMID- 9643192
TI - Dentigerous cyst of mandibular second premolar in a five-year-old girl, related
to a non-vital primary molar removed one year earlier: a case report.
AB - A dentigerous cyst of the mandibular second premolar in a 5-year-old female was
radiographically diagnosed. A non-vital primary predecessor molar had been
removed a year earlier. At that time, the primary molar had been in the mouth for
approximately two years. Although there was the possibility of the premolar being
non-vital, as a consequence of the cystic cavity surrounding it, marsupialization
treatment of the cyst was done, causing a rapid development of the premolar.
Structural irregularities in the enamel and in the first radicular portion were
visible, possibly caused by the very early beginning of the cyst formation.
PMID- 9643193
TI - Oral manifestations of Ellis-van Creveld syndrome: report of two siblings with
unusual dental anomalies.
AB - Ellis-van Creveld syndrome (EvC), also called chondroectodermal dysplasia, is a
rare occurrence inherited as an autosomal recessive disease. Despite the fact
that oral manifestations play an important role in the diagnosis criteria for
EvC, few detailed reports have been published in the dental literature. This
articles presents two siblings with EvC, a boy aged 9 years and a girl aged 7 1/2
years, a product of unaffected first cousin parents. The patients manifests:
chondrodysplasia of tubular bones resulting in disproportionate dwarfism,
polydactyly and syndactyly of hands and feet, severe dystrophic nails, multiple
broad labial frenula with abnormal attachments, congenital missing incisors,
anomalous teeth, bilateral partial clefts of the alveolar bone, and malocclusion.
Other features noted in either cases are: congenital heart defect, median notch
of the upper lip, shovel-shaped incisors and taurodontism. Of the unusual dental
findings observed in our patients are talon cusp, reduced crown size,
supernumerary tooth, and early eruption of teeth. Because half of the cases with
EvC have cardiac malformation, dental treatment must be performed under
prophylactic antibiotic coverage. Dentists play an important role in early
diagnosis and control of dental problem of this condition.
PMID- 9643194
TI - Formaldehyde in dentistry: a review for the millennium.
AB - This article reviews the history and use of formaldehyde in dentistry. Research
from outside the dental field is included, particularly those articles that
pertain to mutagenicity and carcinogenicity. The controversies over the use of
formocresol continue, despite overwhelming research citing deleterious effects.
PMID- 9643195
TI - Treatment of Class III malocclusion with the horseshoe appliance: case reports in
growing patients.
AB - The horseshoe appliance was developed by Dr. Schwarz, and is used to correct
sagittal relationships by elastic force in patients with Class III malocclusion.
The horseshoe appliances minimize the increment of lower anterior facial height
and allow the mandible to be repositioned harmoniously with the soft tissue and
muscle matrix of the jaw. It has the advantages of good patient cooperation, ease
of construction, and effective modification. In patients who were treated with
the horseshoe appliance, the following results were observed: 1. Forward growth
of the maxilla was enhanced, overgrowth of the mandible was restricted, and a
normal arch relationship was established. 2. Minimum downward and backward
rotation of the mandible was accepted with the free sliding of the appliance, and
elastic force and increment of lower anterior facial height were minimized. 3.
Both labioversion of maxillary incisors and linguoversion of mandibular incisors
were observed and facial profile was improved.
PMID- 9643196
TI - Treatment of Class III orthodontic cases in childhood: case report.
AB - Two Class III cases are described which are treated first during childhood with
orthopedics and later by a second stage with orthodontics using bonded braces.
One case was treated solely with a chin cup and the other with a chin cup,
disjunction and anterior traction. Profile and occlusion changes are analyzed and
the orthopedic effect of the treatment is discussed.
PMID- 9643197
TI - The management of premolar supernumeraries in three orthodontic cases.
AB - This paper reviews the incidence, etiology and location of supernumerary teeth
with emphasis on premolar supernumeraries and examines the management of
supernumerary premolars of three patients undergoing orthodontics. These cases
demonstrate that the management of premolars is assessed individually and
treatments based on potential complications, which may occur during the
orthodontic and surgical management of the dentition. Progress and posttreatment
radiographs are recommended for the assessment of late forming supernumerary
teeth.
PMID- 9643198
TI - Suture splint: an alternative for luxation injuries of teeth in pediatric
patients--a case report.
AB - Stabilization of replanted tooth "splinting" is done to prevent further damage to
the pulp and periodontal structure during the healing period. Suture and bonded
resin splint is passive, semirigid and functional splint. It is easy to fabricate
directly in mouth without lengthy laboratory procedures. A case is presented in
which suture and bonded resin splint was performed on laterally luxated maxillary
central incisor and avulsed lateral incisor. The splint was removed after one
week and sufficient periodontal and gingival healing was observed.
PMID- 9643199
TI - Child abuse: attitudes and perceptions of health profession students--a pilot
study.
AB - Child abuse and neglect is a serious social problem with global dimensions. The
purpose of this study was to assess attitudes and perceptions of students of
medicine, dentistry and public health at three Boston institutions about child
abuse and neglect issues that they may encounter in their future professional
lives. Among others, we investigated how participants rank the public health
importance of child abuse and neglect in comparison with violent acts against
other social groups, their willingness to report it and their potential interest
to supplement their knowledge with additional course work. Two hundred and
fourteen students participated in the study by completing our questionnaire. The
results of the statistical analyses indicate that child abuse is considered the
most serious problem, followed by domestic violence, child neglect and abuse of
the handicapped and the elderly. We also documented that a significant
educational need exists in this group, regarding diagnostic methods and
interventions aimed to reduce the incidence and the impact of violence or neglect
against children.
PMID- 9643200
TI - Marsupialization of dentigerous cyst associated with foreign body using 3D CT
images: a case report.
AB - This paper documents a marsupialized dentigerous cyst associated with an amalgam.
The surgical challenge was removing the amalgam from the cystic lining with zero
visibility. To achieve this, the surgical procedure was computer assisted and
used 3D images. Distances between the amalgam and various anatomical landmarks
were assessed in order to define a path from the top of the ridge to the amalgam.
The path was reconstructed at the surgical site and the amalgam removed by
suction. Orthodontic treatment was associated with surgery. Three dimensional
imaging is a useful procedure for deciding on the type of surgical technique
likely to minimize trauma. This report is also a contribution to the literature
by reporting two dentigerous cysts associated with amalgam.
PMID- 9643201
TI - Transposition of maxillary permanent left cuspid tooth: a case report.
PMID- 9643202
TI - Taurodontism in children associated with trisomy 21 syndrome.
AB - Taurodontism, the dental trait characterized by teeth with elongated pulp
chambers and apical displacement of the bifurcation or trifurcation of roots, is
reviewed in children with Trisomy 21 (Down) syndrome. Twenty-two patients were
studied to determine the frequency of taurodontism. Eruption delay and
congenitally lost teeth were also evaluated. While no taurodont teeth were found
in control group in the same age group, the frequency percentage of taurodontism
in our study was found as 66% (p < 0.01, Mann-Whitney test). Results indicate
that taurodontism occurs with a greater than expected frequency in these
patients. This increased frequency may be from a generalized amplified
instability of development.
PMID- 9643203
TI - Late development of maxillary supernumerary tooth: a case report.
AB - A case is presented of a late developing maxillary supernumerary tooth in the
permanent dentition. The patient had a supernumerary tooth fused to a central
incisor in the primary dentition. This case emphasizes the importance of careful
follow-up of patients with a history of supernumerary teeth and, where clinically
indicated, of further radiographic examination.
PMID- 9643204
TI - Fluoride release from fissure sealants.
AB - This 30-day study, compared the amounts and patterns of fluoride release from 5
commercially available fluoride-containing pit and fissure sealants: FluroShield,
Helioseal-F, Ultraseal XT, Baritone L3, and Teethmate-F; Delton without fluoride,
was used as control. Disc-shaped samples of each sealant were immersed in
distilled water and the fluoride release was measured periodically until day 30.
All the fluoridated sealants tested released measurable fluoride throughout the
test period in a similar pattern: the greatest amount of fluoride was released in
the first 24 hours after mixing, fell sharply on the second day and decreased
slowly for the last days. On day one, Baritone L3 released significantly more
fluoride than all other materials. Teethmate-F released the highest amount of
fluoride during all the other time intervals from day 2, until day 30.
PMID- 9643205
TI - The marginal seal of various restorative materials in primary molars.
AB - The use of resin composite restorations in posterior teeth has become an accepted
clinical procedure. Microleakage at the posterior composite/tooth interface is a
major problem. The in vitro quality of the marginal seal was tested in eighty
teeth extracted for orthodontic reasons using a glass-ionomer cement reinforced
with amalgam, two light self-curing glass-ionomer cements and a compomer. All the
teeth were subjected to thermocycling to simulate clinical situation. Compomers
showed the best mechanical and esthetic properties combined with a good marginal
seal.
PMID- 9643206
TI - Cuspal fracture resistance and microleakage of glass ionomer cements in primary
molars.
AB - The purpose of this study was to comparatively evaluate the fracture strength and
microleakage among two new glass ionomer cements. One hundred and ten primary
first and second molars were divided into two main groups, one group comprising
of fifty teeth for microleakage evaluation and second group of sixty for fracture
strength. Both the groups were subdivided equally into four based on the
materials used, consisting of the same number of teeth respectively, in each. Two
controls were used for cuspal fracture strength and an additional trial group was
added for microleakage evaluation. Ideal, non retentive class II were prepared
and restored with amalgam, Fuji IX, Fuji II LC and Vitremer. The statistical
analysis revealed highly significant differences among all the subgroups except
between subgroup 3 vs. 4 and 1 for cuspal fracture strength. Similarly
microleakage values were significantly different statistically among sub groups 4
and 5 vs 1 and 2. The present study revealed that Fuji IX was the best in terms
of cuspal fracture strength and Fuji IX with an additional application of light
cure resin sealant gave the lowest degree of microleakage.
PMID- 9643207
TI - Progression of interproximal caries in the primary dentition.
AB - While studies have addressed the diagnosis and progression of interproximal
carious lesions within a primary tooth, few studies have addressed the
development of proximal lesions in adjacent primary molars. The purpose of this
study was to examine retrospectively the long term interproximal caries
progression in primary molar teeth. Dental records of 150 children were
retrospectively reviewed, 76 from a university pediatric dentistry clinic and 74
from a pediatric dentistry private practice. Out of the 387 teeth initially
diagnosed with proximal caries, the combined university and private practice
results for timing of the development of proximal lesions on adjacent tooth
surfaces showed the following: simultaneous development-162 (41.9%); 1 to 24
months-65 (16.8%); 24 to 60 months-40 (10.3%); never-120 (31.0%). The combined
results for formation of proximal caries in posterior quadrants showed that out
of the 150 patients, the timing for development of additional quadrants with
proximal caries was as follow: simultaneous development: 77 (51.3%); 1 to 24
months 31, (20.7%); 24 to 60 months 25, (16.7%); never 17 (11.3%). The
conclusions of the study are that 69% of the primary molar teeth with proximal
caries developed caries on the adjacent proximal surface and 89% of the patients
who developed a proximal carious lesion on a primary molar tooth within one
quadrant developed another primary molar proximal lesion in another quadrant.
PMID- 9643208
TI - Regressive changes of the dental pulp complex in retained primary molars with
congenitally missing successor teeth.
AB - This study was undertaken to investigate the regressive changes occurring in the
dental pulp complex (pulp, dentin, and cementum) of retained mandibular primary
second molars with congenitally missing bicuspid teeth. Seventeen retained,
caries free, primary molars were used. The specimens were fixed in 10% neutral
buffered formalin. Fixed samples were decalcified, routinely prepared, embedded
in paraffin, sectioned, and stained with hematoxylin and eosin. The results
demonstrated a reduction in the pulp size, abnormal odontoblastic pattern,
declined vascularity, pulp degeneration, pulp stones, accelerated formation of
secondary dentin, and hypercementosis. This study suggests that these findings
may be from aging and physiological defensive changes. These normal, age-induced
changes are of considerable importance in the fields of endodontics,
orthodontics, and pediatric dentistry.
PMID- 9643209
TI - Comparison of two dentin adhesives to primary vs. permanent bovine dentin.
AB - The purpose of this study was to compare the shear bond strengths of two adhesive
systems to the primary and permanent dentin. Labial surfaces of extracted and
frozen bovine mandibular primary incisors and permanent incisors were ground with
#600 grit SiC paper to expose dentin. Bisco Dental Products All Bond 2 (Group
AB2) or Sunmedical Co. Superbond D Liner (Group SDL) tooth surface conditioner
and adhesive were applied and bonded with resin composite. A shear bond strength
(SBS) test was performed and the data were analyzed by an ANOVA (P < 0.05). After
the SBS test, the test surfaces of the dentin and the resin were observed using
SEM. SBS on the primary dentin were significantly higher than those on the
permanent dentin, both in the nonthermal cycled groups and the thermal cycled
groups with the exception of the thermal cycled group of Group SDL. In the
thermal cycled group of Group SDL, there was no significant difference between
SBS on the primary dentin and SBS on the permanent dentin. Bond strengths on the
primary dentin were found to be significantly higher than those on the permanent
dentin, when using All Bond 2 or Superbond D Liner adhesive systems.
PMID- 9643210
TI - The effect of chewing gums on acidogenicity of plaque after a sucrose challenge.
AB - The aim of this investigation was to study the effect of chewing sugared, sugar
free or gum with therapeutic agents like urea or fluoride, on pH of dental plaque
after a sucrose challenge using a microtouch method. The 20 subjects aged 8 to 10
years refrained from toothbrushing for 2 days. Resting plaque pH was recorded,
followed by sucrose 10% (w/v) rinse for 3 min. After 5 min chewing gum was given
and pH recorded at time points of 5, 10, 20, 30 min. Highest plaque pH was found
with Endekay (urea) at all time points followed by fluoride chewing gum; Trident,
and Wrigley's (p < 0.0001). Sucrose 10% w/v (control) showed the maximum drop in
plaque pH when compared to the rest of the groups. The comparative evaluation has
shown Endekay having maximum pH against the acidogenic challenge. Therefore the
present study indicates that chewing gum containing therapeutic agents like urea
may be recommended in high risk caries children.
PMID- 9643211
TI - Cleidocranial dysostosis: report of a case.
AB - This case of cleidocranial dysostosis showed nearly 40 accessory teeth and the
unerupted teeth on radiological examinations. Other diagnostic procedures found
hypoplasia in maxillary and zygomatic bones, deep palate, open fontanel and open
sutures, the collapse of sagittal suture, and aplasia of the clavicle. There were
some abnormalities of the fingers. Under general anesthesia eleven supernumerary
teeth in the mandible and eight in the maxilla were surgically extracted. Upper
and lower removable acrylic appliances were fabricated.
PMID- 9643212
TI - Pediatric malocclusion: early treatment versus late treatment.
PMID- 9643213
TI - The causes of dental erosion.
PMID- 9643214
TI - HIV topic update: salivary testing for antibodies.
AB - Salivary antibody testing for HIV is proving to be a sensitive and specific
procedure, especially useful for epidemiological studies, and has the advantages
of being simple and non-invasive. This paper reviews the field and discusses
antibody testing of dental patients.
PMID- 9643215
TI - Oral disease in Africa: a challenge to change oral health priorities.
AB - Colonial and other unsustainable oral health strategies exported to Africa have
failed to improve oral health in the region. An alternative way of interpreting
and responding to the problems of oral health in Africa is presented. It begins
with a systematic interpretation of the health information available, using the
application of the basic epidemiological principle of defining a specific health
problem by describing its prevalence, severity (morbidity, mortality) and age
adjusted distribution in the population. African oral disease priorities
determined in this way are shown to be fundamentally different from those
perceived previously. It is recommended that this new approach be used in
customising a viable set of oral health policies and intervention strategies for
each individual African community.
PMID- 9643216
TI - Human genes for dental anomalies.
AB - The development of the tooth at gene level is beginning to be understood. This
paper reviews current knowledge and the advances in research on human genes whose
defect leads to dental anomalies. Amelogenesis imperfecta (AI) is a diverse group
of hereditary disorders characterized by a variety of developmental enamel
defects including hypoplasia and hypomineralization, some of which have been
revealed to be associated with defective amelogenin genes. The human amelogenin
genes on X and Y chromosomes have been cloned and investigated extensively.
Although autosomally inherited forms of AI are more common than the X-linked
forms, most studies on the genes causing AI have been performed on the genes of X
linked forms. Recently, the gene for the human tuftelin protein (an enamelin) has
been cloned as a candidate gene for the autosomal forms of AI with another gene
on chromosome 4 involved in some families. Dentinogenesis imperfecta (DI) may be
associated with osteogenesis imperfecta (OI), which is an autosomal dominant bone
disease. Most patients with OI have mutations in either the COLIA1 or COLIA2
genes, which encode the alpha 1(I) or alpha 2(I) subunits of type I collagen, the
major organic component of bone and dentin. Gene defects causing isolated DI have
not been identified. Recently, it was demonstrated that a missense mutation of
MSXI, a human homeobox gene, causes autosomal dominant agenesis of second
premolars and third molars. Data indicating an important function for MSXI, the
mouse counterpart of the human MSXI gene, in mouse tooth development have been
accumulating since 1991. Knockout mice lacking this gene exhibited multiple
craniofacial anomalies including complete tooth agenesis. X-linked anhidrotic
ectodermal dysplasia (EDA), characterized by abnormal hair, teeth, and sweat
glands, was demonstrated to be caused by a mutation in a novel transmembrane
protein gene that is expressed in epithelial cells and in other adult and fetal
tissues. The predicted EDA protein may belong to a novel class of proteins with a
role in epithelial-mesenchymal signaling. Several mutations have been reported in
genes causing hypophosphatasia, which is characterized by defective
mineralization of the skeletal and dental structures.
PMID- 9643217
TI - Parathyroid hormone-related protein (PTHrP) as a regulating factor of
endochondral bone formation.
AB - Parathyroid hormone-related protein (PTHrP) was first identified as a
pathogenetic factor for the hypercalcemia of malignancy. Recently PTHrP is
focused as a physiological paracrine factor regulating cell proliferation and
differentiation in many tissues during fetal and postnatal growth. Evidence for
the skeletal origin of PTHrP comes from several sources and targeted disruption
of the PTHrP gene in mice has resulted in a phenotype with accelerated
endochondral bone formation, suggesting PTHrP as a factor regulating chondrocyte
differentiation. Indian hedgehog, one of the conserved family of hedgehog
regulating segmentation of Drosophila, is found to be an upstream factor of PTHrP
in a regulating pathway of chondrocyte differentiation. Moreover, Bcl-2, a
protein that controls programmed cell death in several cell types, is suggested
to lie downstream of PTHrP in this pathway. A point mutation of PTH/PTHrP
receptor is identified in a patient with Jansen-type metaphyseal chondrodysplasia
and constitutive, ligand independent activation is indicated in this mutant
receptor.
PMID- 9643218
TI - Cancer-promoting effect of Taiwan betel quid in hamster buccal pouch
carcinogenesis.
AB - OBJECTIVE: To investigate the cancer-promoting effect of Taiwan betel quid in
hamster buccal pouch carcinogenesis. MATERIALS AND METHODS: Two hundred and fifty
two non-inbred male adult Syrian golden hamsters were randomly divided into six
groups, each containing forty-two animals. A treatment regimen over a 14-week
experimental period was employed with six animals per group being killed at seven
different periods (every 2 weeks). The right buccal pouch of each animal was
painted three times a week with various combinations of 7,12
dimethylbenz[a]anthracene (DMBA), Taiwan betel quid extract, dimethyl sulfoxide
(DMSO) and mineral oil. RESULT: Both the number and size of tumors in animals
concurrently treated with DMBA and betel quid were significantly higher than
those in animals treated with DMBA alone in each killing period of 8, 10, 12 and
14 weeks. No visible tumors but hyperkeratosis and acanthosis were observed in
pouches treated with betel quid alone for all killing periods. CONCLUSION: Our
results indicate Taiwan betel quid may be a co-carcinogen in human oral
carcinogenesis, if extrapolation can be made from the current animal study.
PMID- 9643219
TI - The association of platelet-derived growth factor (PDGF) receptor tyrosine
phosphorylation to mitogenic response of human osteoblastic cells in vitro.
AB - OBJECTIVES: The purpose of this study was to make clear the relationship of human
osteoblastic cell growth, induced by platelet-derived growth factor (PDGF), to
PDGF receptor tyrosine phosphorylation. MATERIALS AND METHODS: Osteoblastic cells
derived from human maxilla were cultured with human PDGF. The cell growth was
evaluated by cell number and DNA synthesis. PDGF receptor tyrosine
phosphorylation was detected by immunoblot analysis using anti-PDGF receptor
alpha, beta subunits and anti-phosphotyrosine antibodies. Genistein, a tyrosine
kinase inhibitor, was added to the culture to investigate the effect on
osteoblastic cell growth and PDGF receptor tyrosine phosphorylation induced by
PDGF. RESULTS AND CONCLUSIONS: PDGF stimulated the proliferation of human
osteoblastic cells and this effect was synergetic with serum stimulation. DNA
synthesis of osteoblastic cells was elevated by PDGF in a dose dependent manner
at the minimum concentration of 1 ng ml-1. PDGF also induced PDGF receptor
tyrosine phosphorylation within 1 min on osteoblastic cells, and tyrosine
phosphorylation occurred on PDGF receptor subunits alpha and beta. Genistein
inhibited cell growth and receptor tyrosine phosphorylation, which was induced by
PDGF on these cells. In conclusion, human osteoblastic cell growth induced by
PDGF is shown to relate to tyrosine kinase of PDGF receptors.
PMID- 9643220
TI - The use of tretinoin as oral mucositis prophylaxis in bone marrow transplantation
patients: a preliminary study.
AB - OBJECTIVE: The examination of prophylactic efficacy of tretinoin on oral
mucositis, post bone marrow transplantation (BMT). PATIENTS AND METHODS: The
study population consisted of 11 patients undergoing BMT. Six tretinoin topically
treated patients (0.25 mg daily of 0.1% tretinoin cream) were matched with five
non-treated control patients comparing mucositis severity, duration and analgetic
(morphine) requirements. Concomitant follow-up included conditioning parameters
associated with mucositis and engraftment. RESULTS: The mean of oral mucositis
peak scores was significantly lower in the tretinoin-treated patients vs the non
treated patients (score 1.5 vs 3.6; P < 0.02). In the majority of cases the
duration of the most severe phase of oral mucositis was shorter in the tretinoin
treated group as compared with the control. Only one patient in the experimental
group required morphine analgesics compared with four patients in the control
group. CONCLUSIONS: This preliminary study indicates that the severity of oral
mucositis, both objective and subjective, in BMT patients may be reduced by 0.1%
topical tretinoin cream, 0.25 mg, administered daily from the beginning of the
BMT conditioning regimen until marrow engraftment.
PMID- 9643221
TI - Intranodal injection of anticancer drugs into fixed cervical metastatic lymph
nodes.
AB - OBJECTIVE: In patients with head and neck carcinoma, fixed enlarged metastatic
lymph nodes (LNs) are sometimes inoperable and carry an increased risk of
mortality. To control metastatic LNs, we attempted intranodal injection of
anticancer agents. SUBJECTS AND METHODS: Fifteen patients with squamous cell
carcinoma arising in the gingiva (8), tongue (3), floor of the mouth (1), or
maxillary sinus (3) were enrolled. These patients consisted of two groups, those
in the early era in which the fixed LNs of six patients were treated with 60Co
(RA group) and those in the late era in which both radiation and intranodal
injection of anticancer agents were administered to nine patients (IN group).
Intranodal injection consisted of peplomycin, 5-fluorouracil, and cis
diamminedichloroplatinum. RESULTS: In the IN group, LNs regressed from about 40%
to nearly 100%, although two patients showed no appreciable response. The LNs
treated by combination therapy regressed considerably while LNs in the same
patients treated with 60Co alone showed a minor response or grew gradually. In
three patients, the LNs regressed sufficiently to be extirpated safely. The good
clinical response in the locally injected LNs was histologically associated with
distinct evidence of tumor cell degeneration. In the RA group, none of the LNs
responded to radiation with 60Co; one LN exhibited slight regression, but the
others enlarged during and soon after the radiation. Compatible with the clinical
effects, many patients in the IN group demonstrated a good prognosis; three are
alive without disease, and four survived for prolonged periods. However, all
patients in the RA group died due to progression of the positive LNs or pulmonary
complication within 10 months. CONCLUSION: These results indicate that intranodal
injection of anticancer drugs is useful for the management of fixed enlarged LNs.
PMID- 9643222
TI - Characteristics of rheumatoid arthritis patients with self-reported sicca
symptoms: evaluation of medical, salivary and oral parameters.
AB - OBJECTIVES: To examine the prevalence of sicca symptoms in rheumatoid arthritis
(RA)-patients, and to evaluate medical, salivary, and oral parameters in matched
subgroups of patients with and without sicca symptoms as well as in healthy
controls. PATIENTS AND METHODS: The prevalence of self-reported sicca symptoms
was examined by a postal questionnaire in a representative cohort of RA-patients
(n = 105, aged 52-74 years, disease duration 10-20 years, 77% females, 56% RF
positive). Patient subgroups and controls (9-10 in each group) underwent
examinations of disease activity, blood analyses, tests of tear and salivary
secretion, and examination of oral mucosa and microflora. Analyses of salivary
acidic proline-rich proteins (PRPs), statherin and histatins were performed.
RESULTS: One or more sicca symptoms were reported by 65% of RA-patients. Sicca
patients (having > or = 4 sicca symptoms) had a more active and severe disease
with higher scores for disability, fatigue and tender joints than patients
without such symptoms. Other significant findings in the sicca group were lower
values of unstimulated whole saliva, output of PRPs, statherin and histatins in
submandibular saliva, and higher counts of oral Candida species. CONCLUSIONS:
Sicca symptoms were prevalent in RA. Qualitative and quantitative salivary tests
distinguished between sicca and non-sicca RA-patients, though overlap was
considerable for some parameters.
PMID- 9643224
TI - Dental erosions and gastro-oesophageal reflux disease in institutionalized
intellectually disabled individuals.
AB - OBJECTIVE: Both exogenous acids, from the diet, and endogenous acids, from
stomach juice, can dissolve the enamel mineral, resulting in dental erosions.
Gastric acid may reach the mouth by gastro-oesophageal reflux disease (GERD),
recurrent vomiting, rumination and regurgitation. These conditions are frequently
found in the intellectually disabled population. Therefore, we investigated the
presence of dental erosions in combination with GERD among intellectually
disabled inhabitants, with an IQ < 50, taken from three Dutch institutes.
MATERIALS AND METHODS: At random 63 individuals underwent an oesophageal pH test
and dental screening and possible predisposing and attributable factors were
determined. An abnormal pH level was defined as a pH < 4, > 4.5% of the measured
time. Subjects with dental erosions were compared to those without dental
erosions. RESULTS: In 29 out of 63 (46.0%) cases evidence of dental erosions was
found. In 19 of these 29 subjects with erosions (65.5%) GERD was diagnosed,
compared to nine (26.5%) out of 34 subjects without erosions (P = 0.04). In the
subjects with erosions mean duration of pH < 4 was 15.6% (range: 0.5-90.5)
compared to 6.3% (range 0-40.4) in subjects without erosions (P = 0.02). An IQ <
35 was found to be predisposing (P < 0.001). CONCLUSION: In this population of 63
institutionalised intellectually disabled persons dental erosions were diagnosed
in 46%. Sixty-five per cent of them had GERD. Individuals with longer duration of
pH < 4 than 6.3% of the measured time and with an IQ < 35 were at higher risk to
develop dental erosions. This study shows that dental erosions in the
intellectually disabled population might be an oral manifestation of GERD.
PMID- 9643223
TI - Characteristics and responses of EBV immortalized B cells from periodontal
disease patients.
AB - OBJECTIVE: This study was designed to examine human B cell responses to
Actinobacillus actinomycetemcomitans (Aa). The general hypothesis to be tested
was that Epstein-Barr virus (EBV) immortalized B cells could be used to
investigate variations in B cell responsiveness of periodontitis patients to
periodontal pathogens, and that B cells derived from the peripheral blood of
periodontal disease patients infected with Aa demonstrate differences in in vitro
activities compared to periodontally healthy subjects. DESIGN: EBV-transformed B
cell lines were used to analyze immunoglobulin and Aa-specific antibody
responses, as well as to determine the frequencies of cells producing
immunoglobulin (Ig) of a specific isotype and detect clones secreting antibodies
specific for Aa. Lymphoblastoid cells lines (LCL) were derived by clonal
transformation of peripheral blood lymphocytes from 10 Aa-infected patients with
adult periodontitis (Aa-AP) and seven normal subjects. METHODS: The B cells were
incubated in Aa-coated polystyrene plates to separate adherent and non-adherent
cells, and stimulate the cells with the whole bacteria. In addition, the B cells
were stimulated with Aa LPS, E. coli LPS, or the polyclonal B cell activators
(PBAs), pokeweed mitogen (PWM) and Staphylococcus aureus protein A (SpA). Both
adherent and non-adherent cell populations were cultured for up to 15 days. MAIN
OUTCOME MEASURE: Total immunoglobulins (Igs) and antibody (IgG, IgA, IgM) levels
to Aa in the culture supernatants were assessed using an ELISA. The distribution
of IgG, IgA, IgM and Aa-specific antibody producing cells was analyzed by a
double immunoenzymatic staining technique. RESULTS: IgM levels produced by the
LCLs were significantly increased vs IgG and IgA (P < 0.001). Three days after Aa
stimulation, a marked increase in the level of total Igs and Aa-specific antibody
was observed in adherent cells from Aa-AP (P < 0.05-0.03). Aa-specific antibody
levels were significantly higher in the supernatants from Aa-AP vs normals
throughout the culture interval (P < 0.03). There was also a significant increase
in Aa-specific antibody levels after stimulation with Aa LPS or E. coli LPS (P <
0.05), whereas PWM and SpA had no significant effect on antibody to Aa. There was
a predominance of IgM cells compared to IgG and IgA isotypes (P < 0.04) in LCLs
from Aa-infected patients. After stimulation with Aa, a significant increase in
the number of IgA (111%) and IgG (48%) secreting cells was observed, concomitant
with a 74% decrease in the Ig-negative cell population. Total Aa+ cells increased
significantly after stimulation (P < 0.001), predominated by Aa-specific IgG and
IgM antibody producing cells. CONCLUSIONS: These results showed that LCLs from Aa
infected patients were polyclonal with respect to isotype distribution. Further
stimulation with Aa revealed a shift to cytoplasmic IgG and IgA expression, as
well as increases in the Aa-specific B cell population. In contrast, the PBAs
stimulated the LCLs to synthesize primarily IgM. Additionally, the findings
indicated that: (1) without T cells, polyclonal activation of B cells may lead to
elevated Aa-specific B cell populations; and (2) the presence of previously
sensitized B cells is required to exert an antigen specific antibody response in
the LCL. We conclude that secondary activation of primed B cells by oral bacteria
or their products in advanced periodontal lesions may contribute to the local
accumulation of significant numbers of Ig-producing cells. This report also
suggested that EBV-mediated transformation can be used to probe B cell-bacterial
interactions in studies of periodontitis.
PMID- 9643225
TI - Oral Submucous Fibrosis Experts Symposium held at the 5th International Congress
on Oral Cancer. London, 26th September 1997. Abstracts.
PMID- 9643226
TI - Toothpaste, mouthrinse and other topical remedies in periodontics.
PMID- 9643227
TI - The history of oral hygiene products: how far have we come in 6000 years?
AB - How far have we come in the past six millennia? Numerous dental epidemiological
studies indicate that people are keeping their teeth longer than over before in
this century. Agents and devices have evolved, by custom and by research, to
enable people, with professional assistance, to maintain good oral health. Our
diets, our lifestyles and our professional colleagues have "conspired" as
pathogenic influences on oral health. The profession has met the challenge by
developing and perfecting a myriad of devices and agents to thwart these
pathogenic factors. Patient motivation and professional acceptance of preventive
dentistry procedures still remain challenges. We certainly eat well, speak well,
look fine and "smell fresh"--but we also have plaque, gingivitis and dental
caries. The reader can determine how much progress has been made by reflecting on
his or her personal oral health status!
PMID- 9643228
TI - Is the chemical prevention of gingivitis necessary to prevent severe
periodontitis?
AB - Gingival inflammation seldom causes discomfort, social embarrassment or loss of
function. As most sites with gingival inflammation do not progress to severe
periodontal disease, gingivitis should not be considered a public health problem.
Periodontitis is always preceded by gingivitis. But most gingivitis remains
stable for years without progressing to periodontitis. The number of gingivitis
sites that do convert is small. The levels of oral cleanliness achieved by the
majority of populations in industrialized countries are below the threshold for
severe destructive periodontal disease of personal and public health concern.
Because methods of measuring the progression of periodontal disease are
unreliable, definitive answers regarding conversion of gingivitis to severe
periodontitis are lacking. Gingival inflammation frequently remains contained;
most gingivitis remains stable for years without progressing to periodontitis.
Decreasing gingivitis does reduce shallow pocketing, but the effect on severe
periodontitis is not clear. Although the underlying justification for the
reduction of plaque is to reduce gingival inflammation to prevent or reduce
severe periodontitis and tooth loss, the basis for the approach is equivocal. A
reasonably high level of plaque appears to be compatible with acceptably low
levels of periodontal disease. Reducing nonspecific plaque levels to such levels
is therefore a rational goal. The conventional methods of controlling periodontal
disease involve mechanical removal of plaque and calculus. A complimentary
ecological approach, using chemicals, would be to alter the environment of the
pocket to prevent growth of putative pathogens. Any ecological approach should be
sensitive to the dangers of disrupting the natural ecology of dental plaque. Some
antimicrobial and antimetabolic agents such as fluoride, chlorhexidine and
triclosan and zinc citrate can selectively suppress certain organisms or inhibit
bacterial proteases implicated in tissue damage. The uncertainties about factors
that convert gingival inflammation into periodontitis and periodontitis into
severe periodontitis coupled with insufficient data from controlled clinical
trials on the effectiveness of chemical reduction of gingivitis to prevent severe
periodontitis leads one to conclude that more research is required before the
need for the chemical prevention of gingivitis to prevent severe periodontitis
can be justified.
PMID- 9643229
TI - Controlling plaque by disrupting the process of plaque formation.
PMID- 9643230
TI - Gum health product formulations: what is in them and why?
AB - Two dominant factors dictate which ingredients are used in formulating toothpaste
and mouthwashes. The major one is the type of active ingredient chosen,
especially cationic active ingredients such as chlorhexidine; the other factor is
the needs of the consumer. Apart from gum health benefits, the consumer expects
to obtain from gum health toothpaste and mouthwashes other benefits of clean
teeth (abrasive and detergent), fresh breath (antimicrobial agents and flavor)
and protection from caries and possibly tartar. Exhaustive testing involving
experimental design and validated laboratory and clinical tests is essential to
ensure that all these benefits are delivered. Unless products are developed
systematically, then products with relatively poor activity can find their way on
to the market.
PMID- 9643231
TI - Evaluation of oral hygiene products: science is true; don't be misled by the
facts.
AB - Most people in industrialized countries use oral hygiene products. When an oral
health benefit is expected, it is important that sufficient scientific evidence
exist to support such claims. Ideally, data should be cumulative derived from
studies in vitro and in vivo. The data should be available to the profession for
evaluation by publication in refereed scientific journals. Terms and phrases
require clarification, and claims made by implication or derived by inference
must be avoided. Similarity in products is not necessarily proof per se of
efficacy. Studies in vitro and in vivo should follow the basic principles of
scientific research. Studies must be ethical, avoid bias and be suitably
controlled. A choice of controls will vary depending on whether an agent or a
whole product is evaluated and the development stage of a formulation. Where
appropriate, new products should be compared with products already available and
used by the general public. Conformity with the guidelines for good clinical
practice appears to be a useful way of validating studies and a valuable guide to
the profession. Studies should be designed with sufficient power to detect
statistically significant differences if these exist. However, consideration must
be given to the clinical significance of statistically significant differences
between formulations since these are not necessarily the same. Studies in vitro
provide supportive data but extrapolation to clinical effect is difficult and
even misleading, and such data should not stand alone as proof of efficacy of a
product. Short-term studies in vivo provide useful information, particularly at
the development stage. Ideally, however, products should be proved effective when
used in the circumstances for which they are developed. Nevertheless, a variety
of variable influence the outcome of home-use studies, and the influence of the
variable cannot usually be calculated. Although rarely considered, the cost
benefit ratio of some oral hygiene products needs to be considered.
PMID- 9643232
TI - Clinical indications for the use of chemical adjuncts to plaque control:
chlorhexidine formulations.
PMID- 9643233
TI - Chlorhexidine: is it still the gold standard?
AB - After 20 years of use by the dental profession, chlorhexidine is recognized as
the gold standard against which other antiplaque and gingivitis agents are
measured. Chlorhexidine's antiplaque effect is a result of the dicationic nature
of the chlorhexidine molecule, which affords the agent the property of
persistence of antimicrobial effect at the tooth surface, through both
bactericidal and bacteriostatic effects. Although other antiplaque agents may
show either purely immediate effect, or limited persistence, the degree of
chlorhexidine's persistence of effect at the tooth surface is the basis of its
clinical efficacy. Similarly, the cationic nature of the chlorhexidine molecule
is the basis of the most common side effect associated with the use of the agent-
extrinsic tooth staining. Such tooth staining seems to be the result of a local
precipitation reaction between tooth-bound chlorhexidine and chromogens found
within foodstuffs and beverages. The cationic nature of the chlorhexidine
molecule also means that the activity of the agent is rapidly reduced in the
presence of anionic agents, specifically those found within certain types of
toothpaste; thus care is required when using normal toothbrushing alongside
chlorhexidine. By understanding how the chemical properties of the chlorhexidine
molecule can explain the plethora of clinical efficacy and safety data, the use
of chlorhexidine can be optimally aimed towards the patient groups who would most
benefit from the superior therapeutic effect of the agent. Specifically,
chlorhexidine would seem to be of most value to patients in whom the ability to
perform adequate oral hygiene procedures has been compromised. In these
individuals the delivery of the correct dose of chlorhexidine to the tooth
surface can be optimized through the judicial use of the several different
chlorhexidine formulations now available. Thus, by understanding the properties
and limitations of the chlorhexidine molecule, the dental profession can ensure
that the efficacy of the agent is maximized, and the side effects associated with
the agent are minimized, allowing chlorhexidine to rightly remain the gold
standard against which other antiplaque agents are measured.
PMID- 9643234
TI - Metal salts, essential oils and phenols--old or new?
PMID- 9643235
TI - Supragingival calculus and periodontal disease.
PMID- 9643236
TI - Vehicles: how to deliver the goods.
PMID- 9643237
TI - Strategies and agents in supragingival chemical plaque control.
PMID- 9643238
TI - Chemical plaque control--prevention for the masses.
PMID- 9643239
TI - It's all in the sequence: community health.
PMID- 9643240
TI - Esthetic single-tooth replacement with implants: a team approach.
AB - The range of indications for implant-borne prostheses in partially edentulous
patients has expanded in recent years as a consequence of advances in
regenerative techniques for bone and soft tissues. The esthetic demands of both
patients and dentists have risen in parallel with these advances. Esthetic
compromises in prostheses have become increasingly less tolerable, particularly
in the anterior region of the maxilla. If the presenting situation is less than
optimal, extensive preprosthetic measures may be required to prepare local
tissues for acceptance of esthetically and functionally adequate prostheses.
Particularly in difficult situations, collaboration by a team is recommended. The
exchange of ideas and experience among specialists should begin as early as the
treatment planning stage and extend over the entire course of therapy. The
objective should be defined and the various steps of treatment should be
coordinated with participation from all team members.
PMID- 9643241
TI - A retrospective look at esthetic resin composite and glass-ionomer Class III
restorations: a 2-year clinical evaluation.
AB - OBJECTIVE: A restorative material for Class III cavities must, besides being
functional, be esthetically satisfactory, providing good working conditions and
several shade and color options. A clinical evaluation was initiated to compare
the suitability of resin composite and glass-ionomer cement materials for such
restorations. METHOD AND MATERIALS: Forty-two Class III conservative cavities,
esthetically important because of facial extensions, were selected. Resin
composite restorations were placed in 21 cavities, and the remaining 21 were
restored with glass-ionomer cement. The following characteristics were studied:
color or esthetics, anatomic shape, surface texture, staining, marginal
infiltration, dental plaque retention, and occurrence of fracture. After 24
months, the restorations were evaluated. RESULTS: The only statistically
significant difference between the resin composite and glass-ionomer cement
restorations in the experimental period involved color or esthetics. CONCLUSION:
Resin composites and glass-ionomer materials provide excellent functional and
esthetic results in Class III cavities when properly indicated.
PMID- 9643242
TI - The effect of amalgam bonding on resistance form of Class II amalgam
restorations.
AB - OBJECTIVE: This study evaluated the load required to produce failure in Class II
bonded amalgam restorations. METHOD AND MATERIALS: Five groups of 12 maxillary
molars were mounted. Class II mesio-occlusal preparations were cut: group 1,
extension through central grooves, without retention grooves; group 2, proximal
slot preparation, without retention grooves; groups 3 and 5, slot preparation
with long facial and lingual retention grooves; group 4, slot preparation without
grooves, with unsupported proximal enamel allowed to remain. Groups 1 to 4 were
restored with an amalgam-bonding system and amalgam; in group 5, no amalgam
bonding material was used. RESULTS: Mean (SD) failure loads: group 1, 281 (77) N;
group 2, 246 (101) N; group 3, 238 (84) N; group 4, 254 (100) N; and group 5, 191
(66) N. CONCLUSION: Although there was a trend toward greater resistance to
dislodgment or fracture when an amalgam-bonding technique was used, its use did
not significantly increase the resistance to failure when compared to retention
grooves alone.
PMID- 9643243
TI - A retrospective evaluation of a series of dentin-bonded ceramic crowns.
AB - OBJECTIVE: This study assessed the clinical performance of dentin-bonded crowns,
in which ceramic crowns are bonded to underlying dentin with a resin composite
based luting material and a dentin bonding agent. METHOD AND MATERIALS: Twenty
five patients who had received such restorations more than 1 year previously were
recalled for evaluation of their crowns. RESULTS: Sixty dentin-bonded complete
coverage restorations were assessed. Forty-one of the crowns had been placed on
incisor teeth. The mean time since placement of the restorations was 2.43 years.
Fifty-seven of the 60 restorations were intact. The three failures had resulted
from cracks in the restorations, which had not clinically debonded. No secondary
caries was detected at the crown margins, and anatomic form was assessed as
excellent for 56 crowns. Root canal treatment had been required in one case.
Color match was rated very good for 47 crowns. All 25 patients were satisfied
with their restorations. CONCLUSION: Dentin-bonded crowns may be found to have a
low rate of failure and to provide a high level of patient satisfaction.
PMID- 9643244
TI - A comparison of three methods for detecting Candida albicans in patients with
Sjogren's syndrome.
AB - OBJECTIVE: An immediate chairside technique (Latex Candida) for the detection of
Candida albicans was compared with a simple tube culturing technique (Oricult)
and the traditional laboratory culturing technique in patients with Sjogren's
syndrome. METHOD AND MATERIALS: Subjects with primary (n = 9) and secondary (n =
9) Sjogren's syndrome (mean age of 56.7 years; all female) and an age- and sex
matched group of control subjects (n = 9) were selected. Three different methods
for culturing Candida albicans were performed for each subject. One culturette
was plated on a trypticase soy-agar streptomycin-vancomycin medium plate and
incubated for 48 hours at 37 degrees C. Another swab was plated on a reagent
paper with the Latex Candida test kit. The third swab was placed in a culture
media tube using the Oricult kit and incubated for 48 hours at 37 degrees C.
RESULTS: All three techniques indicated a significant difference in the
prevalence of Candida between the control group and both Sjogren's groups. The
Latex Candida technique indicated that 78% of all Sjogren's subjects were
positive for Candida, while the other two tests indicated that 83% were positive.
CONCLUSION: The Latex Candida technique was comparable to Oricult and
streptomycin-vancomycin culturing techniques for negative results and was
correctly positive for 90% of cases.
PMID- 9643245
TI - Use of a resin-ionomer in the treatment of mechanical root perforation: report of
a case.
AB - A perforated root represents a difficult challenge to the clinician, and
treatment of such defects often involves surgical and/or advanced restorative
techniques. This typically requires a series of lengthy, often stressful
appointments, may compromise esthetics, and invariably involves additional costs
to the patient. This case report describes the nonsurgical treatment of separate
mechanical perforations that resulted from the removal of a failed prefabricated
post. The tooth was restored in a minimum number of visits through the use of a
novel application of a resin-ionomer material originally designed for routine
restorative procedures.
PMID- 9643246
TI - The effectiveness of a modified hydrochloric acid-quartz-pumice abrasion
technique on fluorosis stains: a case report.
AB - Endemic dental fluorosis is a form of enamel hypoplasia characterized by moderate
to-severe staining of the tooth surface. Since 1916, numerous investigators have
used hydrochloric acid alone on fluorosis stains. More recently, 18% hydrochloric
acid-pumice microabrasion has been used to achieve color modification. The main
disadvantage of this procedure is the high concentration and low viscosity of
hydrochloric acid, which can cause damage to oral and dental tissues. To
eliminate this problem, quartz particles can be mixed with the hydrochloric acid.
The quartz particles prevent the hydrochloric acid from flowing uncontrollablely
by altering it to a gel-like form. A modified 18% hydrochloric acid-quartz-pumice
abrasion technique was used to remove fluorine stains from vital teeth in a
teenager.
PMID- 9643247
TI - The use of an orthodontic thermoplastic retainer as a provisional anterior
restoration: a case report.
AB - Children who present with extensive fractures of anterior teeth pose a difficult
clinical problem. Pulpal and periodontal injuries must be carefully assessed and
managed. Rapid restoration of the form and contour of the extensively fractured
tooth is advisable, not only to improve esthetics but also to prevent unwanted
tipping or tilting of adjacent teeth and overeruption of opposing teeth. A
modified Essix retainer, simply constructed in the laboratory, can be used to
provisionally restore the extensively fractured anterior tooth.
PMID- 9643248
TI - It's all in the sequence: community health, education, and communications.
PMID- 9643249
TI - Fabrication of an amalgam core using a customized acrylic resin shell.
AB - This article describes a build-up technique that uses a customized acrylic resin
shell for restoring endodontically treated molars that are involved in three-unit
fixed partial denture design. The shell confines the amalgam without impinging on
the periodontium to ensure a proper core foundation, an ideal tooth preparation,
and a more predictable final restoration.
PMID- 9643250
TI - The beginning of the end of the antibiotic era? Part I. The problem: abuse of the
"miracle drugs".
AB - The antibiotic era began in the early 1940s with the clinical use of penicillin.
Subsequent discovery, development, and clinical use of other antibiotics resulted
in effective therapy against major bacterial pathogens. These drugs were so
effective that bacterial infectious diseases were considered by many experts to
be under complete therapeutic control. However, the scientific community grossly
underestimated the remarkable genetic plasticity of these organisms and their
ability, through mutations and genetic transfer, to develop resistance to
antibiotics. Infectious diseases are now the world's major cause of death. The
cause of bacterial reemergence as a threat to human health and life is the abuse
of the "miracle drugs." The ubiquitous nature of antibiotics in the human
ecosystem foments bacterial resistance and threatens to eliminate antibiotics as
effective drugs for human therapeutic use.
PMID- 9643251
TI - The immediate provisional restoration: a review of clinical techniques.
AB - For each patient who requires removal of anterior teeth, there are a multitude of
treatment considerations. Cosmetic demands, functional needs, treatment
sequencing, timeliness, and affordability are some primary concerns that must be
addressed on an individual basis. A patient will generally want a cosmetic and
functional prosthesis at the earliest possible opportunity. Providing the most
appropriate interim prosthesis for a given patient is both challenging and
rewarding. The numerous clinical techniques for immediate interim tooth
replacement are reviewed, and previously unreported methods are presented to
assist the clinician in the selection of interim prosthesis design.
PMID- 9643252
TI - The bonded amalgam restoration: a case report.
AB - The development of resin cements for use in fixed prostheses has suggested the
possibility of a new direct restorative technique, the bonded amalgam. This
restoration technique reportedly reduces microleakage and increases adhesion to
dental structure compared to conventional amalgam restorative techniques. Factors
such as tooth conservation, occlusion, patient age, and the time required for the
execution of this type of restoration should also be considered. An amalgam
restoration was placed with the adhesive technique in a 13-year-old patient with
a nonvital mandibular left second molar and limited interocclusal space. After 3
years of observation, the restoration shows excellent function, suggesting its
appropriateness for special clinical situations.
PMID- 9643253
TI - Biocompatibility of Clearfil Liner Bond 2 and Clearfil AP-X system on nonexposed
and exposed primate teeth.
AB - OBJECTIVE: Recent studies have demonstrated that acid etching of vital dentin and
pulpal tissue does not retard pulpal healing, odontoblastoid cell
differentiation, or dentinal bridge formation when the pulp is capped with
adhesive resins. The purpose of this study was to evaluate the pulpal response in
nonexposed and exposed monkey pulps to treatment with the Clearfil Liner Bond 2
and Clearfil AP-X system. METHOD AND MATERIALS: Class V and Class I cavities in
nonexposed and exposed pulps were observed at 7 or 8, 27, and 97 days. RESULTS:
There were no differences in pulpal inflammation between the Clearfil Liner Bond
2/Clearfil AP-X specimens and calcium hydroxide controls in either Class V or
Class I cavities at the various time periods. CONCLUSION: Clearfil Liner Bond 2
and Clearfil AP-X system is not toxic to either nonexposed or exposed pulpal
tissues when placed according to manufacturer's directions.
PMID- 9643254
TI - Management of the fractured maxillary tuberosity: an alternative method.
AB - The maxillary tuberosity can fracture during extraction of a molar tooth. If a
small bony fragment is affected, the extraction of the tooth and tuberosity
continues; however, a conservative approach is advised if the bony fragment is
large. In a modified blind surgical technique, the tooth is removed without the
fractured bone.
PMID- 9643255
TI - Oligodontia--a case report.
AB - Oligodontia is defined as the congenital absence of six or more teeth, excluding
the third molars. Genetic factors play an important role in oligodontia, which
can occur as an isolated finding or as part of a syndrome. Characteristic dental
symptoms are a reduced number of teeth, a reduction in tooth size, anomalies of
tooth form, and delayed eruption. This article describes treatment of a 6-year
old girl with congenital absence of 16 permanent teeth. Her malocclusion was
corrected by orthodontic therapy, and removable partial dentures were made to
improve esthetics and chewing function.
PMID- 9643256
TI - Hand, foot, and mouth disease: a case report.
AB - Hand, foot, and mouth disease is a viral infection related to coxsackieviruses
A5, A6, A9, and A10, coxsackieviruses B2 and B5, and echovirus 11. It generally
affects children, but this article presents a clinical case of a young woman with
hand, foot, and mouth disease. Patients with this disease have oral and skin
lesions that may be confused with other diseases. The differential diagnosis is
very important because both dental and medical professionals may misdiagnose the
disease and sometimes prescribe an inappropriate medication.
PMID- 9643257
TI - An investigation of the effect of a desensitizing dentifrice on dentinal tubules
in vitro and in vivo.
AB - The effect of Sensodyne dentifrice, which contains strontium chloride
hexahydrate, on the occlusion of dentinal tubules was studied in vivo and in
vitro. Eight premolar teeth scheduled for extraction for orthodontic purposes
were used. Four of the teeth were extracted before Sensodyne application (in
vitro). The other four teeth were treated in vivo and then extracted. A patch of
enamel was removed from all the teeth to expose the dentinal surfaces, and the
smear layer over the exposed area was removed. In the in vivo test, the patients
were instructed to brush their teeth for 1 minute, twice a day, for 2 weeks. The
teeth were then extracted and kept in distilled water until examined by scanning
electron microscope. The in vitro teeth were brushed in the same manner and kept
in distilled water between brushings. Most of the in vitro dentinal tubules were
found to be open, whereas most of the in vivo dentinal tubules were occluded.
PMID- 9643258
TI - It's all in the sequence: practice management.
PMID- 9643259
TI - Five-year clinical performance of porcelain veneers.
AB - OBJECTIVE: The overall clinical performance of porcelain veneers was evaluated at
5 years. METHOD AND MATERIALS: Porcelain veneers were placed on 87 maxillary
anterior teeth in 25 patients (19 to 69 years) by a single operator following a
standardized clinical procedure. At the 5-year recall, esthetics, marginal
performance, vitality, fracture rate, and patient satisfaction were recorded.
RESULTS: At recall, 93% of the veneers were satisfactory without intervention.
The remaining 7% presented clinically unacceptable problems such as recurrent
caries, porcelain fracture, severe clinical microleakage, or pulpal reaction. The
retention rate of the porcelain veneers was 100%, and the maintenance of
esthetics was perfect. Only 14% of the veneers presented excellent marginal
adaptation over the entire outline of the restoration; however, the impact of the
slight marginal defects on the clinical performance was negligible. CONCLUSION:
Labial porcelain veneers offer a reliable and effective procedure for the
conservative treatment of discolored, malformed, and malaligned anterior teeth.
PMID- 9643260
TI - The beginning of the end of the antibiotic era? Part II. Proposed solutions to
antibiotic abuse.
AB - The bacteria causing diseases that are now becoming serious public health threats
are neither strange nor exotic, but rather shockingly familiar. Tuberculosis,
typhoid fever, meningitis, pneumonia, and septicemias are emerging global
threats. The infectious agents causing these serious threats are the same
bacteria identified many decades ago. The only difference is that these and other
microorganisms are no longer killed by the "miracle drugs" that have kept them at
bay for the past six decades. Antibiotic resistance has made potential killers
out of bacteria that previously posed little threat to mankind. The
indiscriminate and reckless use of antibiotics has led to a fast-approaching
crisis in which human dominance of the planet is threatened by single, elementary
cells of the microbial world. Part I of this article detailed the causes of the
crisis. Part II addresses the solutions that are recommended by national and
international authorities and organizations.
PMID- 9643261
TI - Autoclave performance and practitioner knowledge of autoclave use: a survey of
selected UK practices.
AB - OBJECTIVE: It is essential that the dental surgery autoclave be tested regularly
to ensure that it is operating at a temperature and pressure that will kill all
microorganisms. The aims of this study were to investigate the knowledge of
general dental practitioners on aspects of autoclave use, to examine their
autoclaving routines, and to test the effectiveness of the sterilization cycle of
their practice's autoclave. METHOD AND MATERIALS: A 35-question questionnaire was
distributed to 840 dental practitioners in the United Kingdom. They were also
sent three spore test ampules with details of their function and instructions on
their use. The practitioners were asked to use the spore test ampules in their
own practice's autoclave and to return these for testing. RESULTS: Four hundred
one questionnaires and associated spore test ampules were returned for analysis,
a 47.7% response rate. Eight practice autoclaves (2.0%) failed to sterilize the
spores. These practices were offered a retest following counseling. A total of
77.8% of respondents had received formal training in infection control. Of the
71.3% of respondents who stated that they check the performance of their
autoclave routinely, 31.5% use a chemical strip every cycle, 17.5% use it once
per day, and 30.4% use it once per week. However, only five respondents (1.2%)
use a spore test; two of these respondents use it every cycle, one once per day,
and two once per week. CONCLUSION: Further education of practitioners may be
necessary to enhance their awareness of the need for routine checking of
autoclave effectiveness.
PMID- 9643262
TI - Fenestration gingival defect in erupting permanent mandibular incisors: a case
report.
AB - Bilateral fenestration of the labial gingival tissue of the permanent mandibular
central incisors is described. The situation was followed over a 2-year period
with no treatment other than prophylaxis and oral hygiene instruction. The final
outcome was an apical positioning of the gingival margin, which was lower than
that of the adjacent uninvolved teeth.
PMID- 9643264
TI - Tobacco: addiction, oral health, and cessation.
PMID- 9643263
TI - Incomplete fractures in intact bilateral maxillary first molars: a case report.
AB - A case of incomplete fractures occurring bilaterally in intact maxillary first
molars is described. The etiology, diagnosis, and treatment of incomplete tooth
fractures are discussed. The clinical results in this case showed that early
diagnosis and treatment can prevent further extension of the crack into the pulp
and subsequent complete tooth fracture.
PMID- 9643265
TI - Helping patients quit smoking: lessons learned in the trenches.
AB - Cigarette smoking is a genuine and complex addiction that involves three
interconnecting links: the central link, nicotine (physiologic) addiction, is
joined to two additional links, psychologic (cognitive and affective) dependence
and sociocultural (environmental) factors. It is precisely this dynamic
combination of related factors that makes cigarette smoking so incredibly
resistant to long-term extinction. Successful management of highly dependent
smokers requires that clinicians use a structured, multifaceted, patient-oriented
approach that includes the use of nicotine replacement and nicotine withdrawal
therapy, intensive monitoring, and long-term follow-up. In this article, the
author offers practical advice gleaned from 30 years of practical experience and
one-on-one contact with 400 patients who have attempted to quit smoking during
the past 5 years at the Indiana University Nicotine Dependence Program.
PMID- 9643266
TI - Smoking cessation.
PMID- 9643267
TI - Tobacco cessation in the dental office: a brief intervention for spit tobacco
users.
PMID- 9643268
TI - Get active about passive smoking in 1998.
PMID- 9643269
TI - Coxsackievirus genome in myocardium of patients with arrhythmogenic right
ventricular dysplasia/cardiomyopathy.
AB - Enteroviruses are known as major infectious agents for inflammatory heart
diseases such as myocarditis and dilated cardiomyopathy (DCM). Arrhythmogenic
right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by replacement
of right ventricular myocardium by fatty and fibrous tissue. In about 65% of
patients inflammatory infiltrates suggest an inflammatory or infectious
etiopathogenesis. To test this hypothesis, we investigated endomyocardial
biopsies of patients with ARVC, with myocarditis or DCM, and from patients with
non-inflammatory cardiac disorders for the presence of enteroviral genome.
Enteroviral RNA with homology to coxsackieviruses type B was detected in 3 of 8
patients with ARVC (37.5%), in 7 of 23 patients with myocarditis or DCM (30.4%),
but in none of 5 patient with non-infectious myocardial diseases (p < 0.05
compared to ARVC patients). These results support earlier suggestions that
coxsackievirus infection of the myocardium is possibly related to the
pathogenesis of ARVC.
PMID- 9643270
TI - Disrupted mobile aortic plaques are a major risk factor for systemic embolism in
the elderly.
AB - Protruding aortic plaques--especially those with mobile properties--on
transesophageal echocardiography (TEE) are a potential source of stroke and
systemic embolism in the elderly. Whether the various morphologies of atheromas
with mobile components represent potential differences in the risk for embolic
events has not been thoroughly elucidated. The goal of the present study was to
determine the association between embolic events and the various types of mobile
lesions in the thoracic aorta. Our population consisted of 569 consecutive
patients (age 18-83 years) referred for TEE over 27 months; 108 (19%) of them
were referred to evaluate recent embolism (cerebral in 97 and peripheral or both
in 11; group I) and the remaining 461 were admitted for reasons unrelated to
embolism (group II). In group I, 35 patients (32%) exhibited protruding plaques;
those were fixed in 10 (9%) and with a mobile component in 25 (23%). In group II,
plaques were found in only 13 patients (3%); fixed in 9 (2%) and mobile in 4 (1
%). Twenty-four patients with mobile lesions in group I were > 50 years old, and
21 of them (88%) were > 60 years old. While the presence of fixed plaques was
associated with a moderate increase in the risk for systemic embolism (adjusted
odds ratio 4.1; 95% confidence interval 1.3-56.4), mobile lesions were linked to
a striking augmentation of this risk (odds ratio 30.1; 95% confidence interval
7.8-132.6). The majority of mobile lesions (76%) in group I represented disrupted
atheromas with characteristic ulcerations or echolucency within the plaque
suggestive of intraatheroma hemorrhage, whereas these TEE features were not
observed in 89% of the mobile lesions in group II (p = 0.0003). We conclude that
among the various types of mobile aortic lesions, the disrupted protruding
plaques are a major risk factor for stroke and embolic events in the elderly.
PMID- 9643271
TI - Surgical treatment of the coronary artery to pulmonary artery fistulas in adults.
AB - Coronary artery to pulmonary artery fistula (CA-PAF) is a rare congenital
anomaly. The purpose of this retrospective study was to analyze 11 adult patients
with CA-PAFs treated surgically, and to evaluate the surgical management and long
term results. There were no surgical deaths and all patients survived the follow
up periods (mean 7.2 years). All symptomatic patients improved their New York
Heart Association functional class. As surgical correction is safe and effective,
with good long-term results, all the patients with CA-PAF in adults can be
candidates for surgery to prevent life-threatening complications.
PMID- 9643272
TI - Assessment of functional results after percutaneous transluminal coronary
angioplasty by cardiopulmonary exercise test.
AB - Twenty-nine patients with documented coronary artery disease underwent
cardiopulmonary exercise tests before and following a percutaneous transluminal
coronary angioplasty (PTCA). The patients medication regimen and exercise
protocols remained the same in both cases. Following PTCA, significant
improvement (p < 0.001-0.0001) was noted in oxygen consumption (1,526.8 +/- 470.0
vs. 1,686.2 +/- 390 ml/min), oxygen pulse (12.40 +/- 2.73 vs. 13.44 +/- 2.9
ml/beat), oxygen pulse score (7.62 +/- 1.29 vs. 8.85 +/- 1.26 points) and in the
ventilatory anaerobic threshold (993.1 +/- 177.6 vs. 1,089.8 +/- 150.9 ml/min)
but not (p > 0.05) in maximal heart rate (128.7 +/- 16.9 vs. 132.0 +/- 17.2
beats/min). Thus, a cardiopulmonary exercise test is an effective method to
assess functional results following PTCA.
PMID- 9643273
TI - A comparison of the effects of mibefradil and atenolol on regression of left
ventricular hypertrophy in hypertensive patients.
AB - OBJECTIVE: This study was designed to compare the effect of mibefradil, a
selective T-type calcium channel antagonist, with the beta-blocker atenolol on
regression of left ventricular (LV) hypertrophy in hypertensive patients.
METHODS: In this multicenter, double-blind, active-controlled, randomized,
parallel-group comparison, 66 patients with mild-to-moderate hypertension
(sitting diastolic blood pressure, SDBP, 95-114 mm Hg) and LV mass index > 102
g/m2 for males and > 88 g/m2 for females were randomized to an initial treatment
with 50 mg of either mibefradil or atenolol for 4 weeks. Doses were increased to
100 mg/day if blood pressure was not normalized to < or = 90 mm Hg, and, if
needed, 25 mg of hydrochlorothiazide was added. Treatment continued for a total
of 24 weeks. LV hypertrophy was assessed by echocardiography, and trough SDBP and
adverse events were recorded. RESULTS: Treatment with mibefradil or atenolol
resulted in decreases from baseline in LV mass index of 11.1% (p < 0.001) and
9.1% (p < 0.001), respectively. The treatment difference (mibefradil vs.
atenolol) was not statistically significant. Reductions in SDBP with mibefradil
and atenolol were 14.3 and 10.7 mm Hg, respectively, again not statistically
significant. Both drugs were well tolerated; however, overall there were more
potentially drug-related adverse events reported with atenolol (48.5%) than with
mibefradil (24.2%). CONCLUSIONS: The reductions in LV hypertrophy and blood
pressure achieved with mibefradil were larger but statistically equivalent to
those with atenolol, but a lower overall incidence of treatment-related adverse
events was seen in the mibefradil-treated patients.
PMID- 9643274
TI - Antihypertensive treatment in postmenopausal women: results from a prospective,
randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril)
with a diuretic (hydrochlorothiazide).
AB - The present study was designed to compare the safety and efficacy of the new
angiotensin-converting enzyme inhibitor moexipril with that of
hydrochlorothiazide (HCTZ) in postmenopausal women with mild-to-moderate
hypertension. After a 4-week single-blind placebo period, 97 postmenopausal
hypertensive women (42-74 years of age) with a sitting diastolic blood pressure
(SDBP) of 95-114 mm Hg were randomized to receive either once daily moexipril 15
mg or HCTZ 25 mg for a 12-week double-blind treatment period. At study endpoint,
HCTZ caused significantly greater increases from baseline in serum uric acid
levels than did moexipril (0.8 +/- 0.1 vs. 0.1 +/- 0.1 mg/dl, p < 0.01).
Furthermore, 12-week treatment with HCTZ resulted in significant increases in
glucose (+11.0 +/- 4.1 mg/dl) and total cholesterol/HDL ratio (+0.3 +/- 0.1
mg/dl) and a significant decrease in HDL (-3.2 +/- 0.7 mg/dl). In contrast,
moexipril treatment was not associated with significant changes in any metabolic
parameter. Both drugs efficiently lowered SDBP with reductions of -10.0 +/- 1.3
and -11.8 +/- 1.1 mm Hg in the moexipril and HCTZ group, respectively. Clinical
adverse events were reported by a greater percentage of HCTZ patients (53%) than
moexipril patients (40%), with headache and rhinitis as the most frequent events.
The results indicate that moexipril was better tolerated than HCTZ in
postmenopausal women and did not adversely affect metabolic parameters. Both
drugs were effective in lowering blood pressure.
PMID- 9643275
TI - Absence of a seasonal variation in myocardial infarction onset in a region
without temperature extremes.
AB - To evaluate whether the incidence of acute myocardial infarction (AMI) attack
would have circadian, weekly and monthly variations in a subtropical area, 540
consecutive patients with AMI who were admitted to our coronary care units were
analyzed. Six-hour intervals over 24 h, daily intervals in a week (7 days) and
monthly intervals in a year (12 months) were studied, respectively. Results
showed that there was a circadian variation in the onset of AMI with a morning (6
a.m. to noon) peak (34%, p < 0.01) but no secondary late evening (18-24 p.m.)
peak. The incidence of AMI was significantly lower on Sundays (9%) than on the
other weekdays (Monday through Saturday; p < 0.05). However, no monthly and
seasonal variations in the incidence of AMI (no winter or summer peaks) were
observed in this series. This study demonstrated a circadian variation in the
onset of AMI attack with a predominant morning peak. The fewer AMI cases on
Sundays compared to the other weekdays suggested that freedom from 'stress' or
'work-load' on Sundays might have an important impact on this low incidence of
AMI. Unlike the large ranges in cold or hot weather found in temperate regions,
the warm climate of a subtropical region does not affect the frequency of AMI.
PMID- 9643276
TI - Limitation of left ventricular hypertrophy and dysfunction by ACE inhibition
after anterior Q-wave myocardial infarction.
AB - To determine whether limitation of left ventricular (LV) hypertrophy with
angiotensin-converting enzyme inhibition after myocardial infarction (MI) is
associated with improved systolic and diastolic function, quantitative two
dimensional echocardiograms and Doppler of 40 patients, who were randomized on
day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg
t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson's rule) and
mass (3D reconstruction), remodeling parameters and peak early (E) and late (A)
transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6
months and 1 year. Compared to placebo over 1 year, captopril limited (p < 0.001)
the increase in diastolic volume and mass, increased LV ejection fraction and
diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct
expansion and aneurysm frequency but volume/ mass ratio was unchanged. Captopril
over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and
hypertrophy and improved both systolic and diastolic function up to 1 year.
PMID- 9643277
TI - Long-term effects on cardiac output and peripheral resistance in patients treated
with enalapril after acute myocardial infarction. CONSENSUS II Multi-Echo Study
Group. Cooperative New Scandinavian Enalapril Survival Study.
AB - In the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II), in
which enalapril treatment was initiated intravenously within 24 h after acute
myocardial infarction, there was a neutral effect on 6-month mortality, whereas a
beneficial effect on the progression of congestive heart failure was noted. We
studied the effect of enalapril on left ventricular systolic function in terms of
cardiac output and mean acceleration time measured by pulsed-wave Doppler in the
left ventricular outflow tract and peripheral resistance. Early angiotensin
converting enzyme inhibition after acute myocardial infarction did not result in
a general improvement of cardiac output. However, a small increase in cardiac
output was observed in a subgroup of enalapril-treated patients with ejection
fraction > or = 45%, probably due to a reduction in peripheral resistance in
these patients.
PMID- 9643278
TI - Accuracy of exercise-induced left axis QRS deviation as a specific marker of left
anterior descending coronary artery disease.
AB - In this prospective study, we examined the diagnostic accuracy of exercise
induced left QRS axis deviation as a marker of LAD coronary artery stenosis. The
mean frontal QRS axis of 66 consecutive patients with chest pain and exercise
induced ST segment depression referred for diagnostic coronary angiography was
analyzed and related to the angiographic findings. An exercise-induced leftward
QRS axis deviation was found in 9/40 patients with and 0/26 patients without
obstructive (> or = 70%) LAD disease (sensitivity 23%, specificity 100%, p =
0.025). In 7 of the 9 patients with left axis deviation, the lesion was proximal
to and in 2 in the region of the first septal perforator. Inclusion of patients
with 0 degrees exercise-induced QRS axis deviation provided a more sensitive but
less specific marker of LAD disease [sensitivity 53% (21/40), specificity 81%
(21/26), p = 0.015]. The findings were similar in patients with single and with
multivessel coronary artery disease. Grouping all patients in the present
prospective and two previous retrospective studies (n = 165), the sensitivity was
29% and specificity 100% (p < 0.0001). Exercise-induced left QRS axis deviation
was a highly specific marker of LAD coronary artery stenosis.
PMID- 9643279
TI - Atrial fibrillation: a delayed presentation of traumatic tricuspid valve
incompetence.
AB - Isolated tricuspid valve incompetence resulting from blunt thoracic injury is
rare. The diagnosis may be challenging. Subsequent clinical course may be
variable. Early surgical intervention rather than medical therapy has been
suggested in selected cases. We report a case of blunt chest trauma causing
delayed chronic tricuspid regurgitation manifesting primarily as atrial
fibrillation many years after the initial blunt chest trauma. Replacement of
tricuspid valve restored normal sinus rhythm.
PMID- 9643280
TI - Behcet's disease ('Silk Route disease') and mitral valve prolapse.
PMID- 9643281
TI - Medical genetics in the UK and the National Health Service.
PMID- 9643282
TI - "Code of practice and guidance on human genetic testing services supplied direct
to the public". Advisory Committee on Genetic Testing.
PMID- 9643283
TI - A population study of mutations and LOH at breast cancer gene loci in tumours
from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2
linked breast cancer in Iceland.
AB - The majority of breast cancer in high risk families is believed to result from a
mutation in either of two genes named BRCA1 and BRCA2. A germline defect in
either gene is usually followed by chromosomal deletion of the normal allele in
the tumour. In Iceland two recurrent mutations have been identified, 999del5
BRCA2 and G5193A BRCA1. In this study, randomly selected pairs of sisters
diagnosed with breast cancer at the age of 60 years or younger were analysed to
evaluate the proportion of breast cancer resulting from BRCA1 and BRCA2.
Genotypes and allele loss in tumour tissue from 42 sister pairs were compared
using markers within and around the BRCA1 and BRCA2 genes. Eleven sister pairs
were highly suggestive of BRCA2 linkage, and no obvious BRCA1 linkage was seen.
Screening for the G5193A BRCA1 and 999del5 BRCA2 mutations showed the 999del5
mutation in the 11 BRCA2 suggestive pairs plus three pairs less indicative of
linkage, and the G5193A BRCA1 mutation in one pair. When known mutation carriers
are removed from the group, no indication of further linkage to BRCA1 or BRCA2 is
seen. The results of our studies suggest that a large proportion of familial
breast cancer in Iceland is the result of the 999del5 BRCA2 mutation, and it is
unlikely that BRCA1 and BRCA2 germline mutations other than 999del5 and G5193A
play a significant role in hereditary breast cancer in Iceland. Furthermore it
can be concluded that most families with BRCA1 or BRCA2 linkage are easily
identified by studying LOH around the defective gene in as few as two affected
relatives.
PMID- 9643284
TI - Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for
more severe disease associated with truncating mutations.
AB - Blood samples from 125 unrelated families with classical type 2 neurofibromatosis
(NF2) with bilateral vestibular schwannomas have been analysed for mutations in
the NF2 gene. A further 17 families fulfilling modified criteria for NF2 have
also been analysed. Causative mutations have been identified in 54 (43%)
classical families and six (35%) of those fulfilling modified criteria. Forty-two
cases from 38 families with truncating mutations had an average age at onset of
symptoms of 19 years and diagnosis at 22.4 years. Fifty-one cases from 16
families with splice site mutations (15 from six), missense mutations (18 from
six), and large deletions (18 from five) had an average age of onset of 27.8
years and at diagnosis of 33.4 years. Subjects with truncating mutations were
significantly more likely to have symptoms before 20 years of age (p<0.001) and
to develop at least two symptomatic CNS tumours in addition to vestibular
schwannoma before 30 years (p<0.001). There were also significantly fewer
multigenerational families with truncating mutations. Four further truncating
mutations were in mosaic form and were associated with milder disease than other
similar mutations. This large study has confirmed the previous impression that
truncating mutations are associated with severe disease, but caution has to be
exercised in using mutation type to predict disease course.
PMID- 9643285
TI - A silent mutation, C924T (G308G), in the L1CAM gene results in X linked
hydrocephalus (HSAS).
AB - The L1 cell adhesion molecule (L1CAM) is a neuronal gene involved in the
development of the nervous system. Mutations in L1CAM are known to cause several
clinically overlapping X linked mental retardation conditions: X linked
hydrocephalus (HSAS), MASA syndrome (mental retardation, aphasia, shuffling gait,
adducted thumbs), spastic paraplegia type I (SPG1), and X linked agenesis of the
corpus callosum (ACC). In an analysis of a family with HSAS, we identified a C-
>T transition (C924T) in exon 8 that was initially thought to have no effect on
the protein sequence as the alteration affected the third base of a codon
(G308G). Extensive analysis of the other 27 exons showed no other alteration. A
review of the sequence surrounding position 924 indicated that the C-->T
transition created a potential 5' splice site consensus sequence, which would
result in an in frame deletion of 69 bp from exon 8 and 23 amino acids of the
L1CAM protein. RT-PCR of the RNA from an affected male fetus and subsequent
sequence analysis confirmed the use of the new splice site. This is the first
report of a silent nucleotide substitution in L1CAM giving rise to an alteration
at the protein level. Furthermore, it shows that as mutation analysis plays an
ever more important role in human genetics, the identification of a synonymous
base change should not be routinely discounted as a neutral polymorphism.
PMID- 9643286
TI - A polymorphism of the CC16 gene is associated with an increased risk of asthma.
AB - Several quantitative traits associated with the asthma phenotype have been linked
to markers on chromosome 11q13, although the gene responsible has yet to be well
established. The gene for Clara cell secretory protein (CC16) is an ideal
candidate for involvement in an inherited predisposition to asthma because of its
chromosomal location, the role of the CC16 protein in controlling airway
inflammation, and differences in levels of the protein between asthmatics and
healthy controls. All three CC16 exons were screened in an unselected population
of 266 subjects from 76 families and a cohort of 52 severely asthmatic children.
A combination of single strand conformational polymorphism (SSCP) analysis,
heteroduplex analysis, DNA sequencing, and restriction digestion was used.
Mutation detection methods identified an adenine to guanine substitution in the
CC16 gene at position 38 (A38G) downstream from the transcription initiation site
within the non-coding region of exon 1. In the unselected population, 43.6% were
homozygous for the polymorphic sequence (38GG) and 46.2% were heterozygous
(38AG). All the asthmatic and unaffected children from both populations were
selected for an unmatched case control analysis consisting of 67 asthmatic and 46
unaffected subjects. Those homozygous for the published sequence (38AA) had a 6.9
fold increased risk of developing asthma (p=0.049) and heterozygotes (38AG) a 4.2
fold increased risk (p=0.028). Modelling of genotype as a continuous covariate
indicated evidence of a significant linear trend across the three genotypes (odds
ratio=2.84 per unit increase in genotype code, p=0.018). These associations were
independent of age, gender, and tobacco smoke exposure. These data and the known
anti-inflammatory role of CC16 in the respiratory tract suggest that alteration
to the gene at position 38 may contribute to asthma.
PMID- 9643287
TI - Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.
AB - A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene
deletions by comparing patient and parent genotypes at 10 intragenic polymorphic
loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases),
five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion.
These five patients did not have severe NF1 manifestations, mental retardation,
or dysmorphic features, in contrast to previous reports of large NF1 deletions.
All five deletions were de novo and occurred on the maternal chromosome. However,
two patients showed partial LOH, consistent with somatic mosaicism for the
deletion, suggesting that mosaicism may be more frequent in NF1 than previously
recognised (and may have bearing on clinical severity). We suggest that large NF1
deletions (1) are not always associated with unusual clinical features, (2) tend
to occur more frequently on maternal alleles, and (3) are an important mechanism
for constitutional and somatic mutations in NF1 patients.
PMID- 9643288
TI - A rapid, PCR based test for differential molecular diagnosis of Prader-Willi and
Angelman syndromes.
AB - Approximately 98% of Prader-Willi syndrome (PWS) and 80% of Angelman syndrome
(AS) cases have deletions at a common region in chromosome 15q11-13, uniparental
disomy for chromosomes 15 (UPD15), or mutations affecting gene expression in this
region. The resulting clinical phenotype (PWS or AS) in each class of mutation
depends upon the parent of origin. Both disorders are characterised at the
molecular level by abnormal methylation of imprinted genes at 15q11-q13 including
the small nuclear ribonucleoprotein N gene (SNRPN). Current diagnostic strategies
include high resolution cytogenetics, fluorescence in situ hybridisation (FISH),
Southern blot hybridisation, or microsatellite typing. We have developed a novel
and rapid diagnostic test for PWS and AS based on differential digestion of
expressed (paternally imprinted) SNRPN sequences by the methylation sensitive
endonuclease NotI or repressed (maternally imprinted) SNRPN sequences by the
methylation requiring nuclease McrBC, followed by PCR amplification of the SNRPN
promoter. We have evaluated this test by blinded analysis of 60 characterised DNA
samples (20 PWS, 20 AS, and 20 unaffected controls). SNRPN sequences could not be
amplified from PWS patient DNA which had been digested with McrBC, nor from AS
patient DNA which had been digested with NotI. We were able to make a correct
diagnosis of PWS, AS, or unaffected in all 60 samples tested. This novel test is
rapid and has a high specificity and sensitivity for deletion and UPD15 cases.
These features make this new test suitable as the initial step in a molecular
diagnostic strategy for PWS/AS.
PMID- 9643289
TI - A survey of phenotypic features in juvenile polyposis.
AB - Solitary juvenile polyps are quite frequent in children, but juvenile polyposis
(JP) is a rare autosomal dominant trait characterised by the occurrence of
numerous polyps in the gastrointestinal tract. Extracolonic phenotypic
abnormalities are well documented in patients with familial adenomatous polyposis
and Peutz-Jeghers syndrome and can allow a clinical diagnosis to be made before
the bowel pathology becomes available. Though described, characteristic
extracolonic abnormalities have not been clearly defined in juvenile polyposis.
We sought to determine whether there are consistent extracolonic phenotypic
abnormalities in JP patients and how frequently this would allow diagnosis of one
of the genetic syndromes known to be associated with juvenile polyposis. Twenty
two JP patients underwent clinical examination and data from one patient were
obtained from case notes. Those consenting to further investigations had x rays
of the skull, chest, and hands and an echocardiogram if clinically indicated.
Significant extracolonic phenotypic abnormalities were present in 18 patients (14
male and four female), and included dermatological (13), skeletal (16),
neurological (5), cardiopulmonary (4), gastrointestinal (3), genitourinary (4),
and ocular (1) features. In five patients the diagnosis of a genetic syndrome was
possible: two had Bannayan-Riley-Ruvalcaba syndrome, two had Gorlin syndrome, and
one had hereditary haemorrhagic telangiectasia (HHT, also known as Osler-Rendu
Weber syndrome). Other patients had some features of these conditions and of
Cowden and Simpson-Golabi-Behmel syndromes, but these were not sufficient to
allow a definitive diagnosis.
PMID- 9643290
TI - Maternal age specific risk rate estimates for Down syndrome among live births in
whites and other races from Ohio and metropolitan Atlanta, 1970-1989.
AB - Our primary objective was to estimate, by one year and five year intervals,
maternal age specific risk rates for Down syndrome among whites and among other
races from two different populations, metropolitan Atlanta and south west Ohio,
using live birth and prenatally diagnosed cases ascertained during 1970-1989. The
five year estimates were also calculated separately for each of the five four
year periods during these 20 years. Additionally, we compared two different
methods of estimating these risk rates by using a third population of whites, and
compared two different statistical methods of smoothing the risk rates. The
results indicate good agreement between the metropolitan Atlanta and south west
Ohio estimates within races, but show a statistically significant difference
between the two race categories. Because 86% of live births in the "other races"
category in the combined population are to blacks, these data may be seen as the
first estimates of maternal age specific risk rates for Down syndrome among
blacks calculated by one year intervals. We found excellent agreement in the risk
rate estimates among the five four year time periods, between the estimates
obtained by using the two different methods of estimation, and between the
estimates obtained using the two different methods of statistical smoothing. Our
estimated risk rates for white women in their 20s strongly reinforce those from
previous studies currently being used for genetic counselling purposes. While we
did find somewhat higher rates for women under 20, and increasingly higher rates
for those over 30 years of age, these differences are not substantial. Thus, this
study in general supports the risk rates estimated from data collected mostly
during the 1960s and 1970s.
PMID- 9643291
TI - Duplication of 8p23.1: a cytogenetic anomaly with no established clinical
significance.
AB - We present seven families with a cytogenetic duplication of the short arm of
chromosome 8 at band 8p23.1. The duplication has been transmitted from parents to
offspring in four of the seven families. In three families, the source of the
extra material and its euchromatic origin were established using FISH with a YAC
which was mapped to 8p23.1 and a whole chromosome paint for chromosome 8. FISH
signals from this YAC were significantly larger on the duplicated chromosome
compared with the normal chromosome in all six family members tested. Comparative
genomic hybridisation (CGH) on a representative subject was consistent with these
results. The families were ascertained for a variety of mostly incidental reasons
including prenatal diagnosis for advanced maternal age. The transmission of this
duplication by multiple phenotypically normal family members with no history of
reproductive loss suggests the existence of a novel class of 8p23.1 duplications,
which can be regarded as euchromatic variants or duplications with no phenotypic
effect.
PMID- 9643292
TI - Meckel syndrome.
AB - Meckel syndrome (MKS) is a lethal syndrome with a central nervous system
malformation, usually occipital meningoencephalocele, bilaterally large
multicystic kidneys with fibrotic changes of the liver, and polydactyly in most
cases. Additional anomalies are frequent. A common characteristic of the
parenchymal changes of many organs is a proliferation of the stromal connective
tissue and increase and dilatation of the associated epithelial ducts. Autosomal
recessive inheritance is well confirmed and the gene locus has been mapped to
chromosome 17q21-24 by genome wide linkage study. The locus was later refined to
within a less than 1 cM region (17q22), in which most of the Finnish MKS patients
share a common chromosomal haplotype suggesting one major and relatively old
mutation. However, in most of the non-Finnish MKS families studied, this linkage
could not be confirmed. The linkage studies provide evidence that more than one
locus is involved in bringing about the combination of CNS malformations, cystic
kidneys, and polydactyly, maybe even in typical cases of MKS. Prenatal diagnosis
of MKS by vaginal ultrasound scan is possible from 11-12 weeks of pregnancy,
especially in families where there is a known risk. In those families where
linkage to 17q22 is established, prenatal diagnosis by DNA analysis is possible.
PMID- 9643293
TI - Linkage and association of an interleukin 4 gene polymorphism with atopic
dermatitis in Japanese families.
AB - We examined linkage between markers at and near the IL4 gene and atopic
dermatitis (AD) in 88 Japanese nuclear families. Affected sib pair analysis
suggested linkage between the IL4 gene and AD (SPLINK lod=2.28). Transmission
disequilibrium testing showed a significantly preferential transmission to AD
offspring of the T allele of the -590C/T polymorphism of the IL4 gene (p=0.001).
A case-control comparison suggested a genotypic association of the TT genotype
with AD (odds ratio=1.88, p=0.01). Since the T allele was reported to be
associated with increased IL4 gene promoter activity compared with the C allele,
our data indicate that genetic differences in transcriptional activity of the IL4
gene influence AD predisposition, particularly in Japanese, because of a high
frequency of the T allele.
PMID- 9643294
TI - A lethal skeletal dysplasia with features of chondrodysplasia punctata and
osteogenesis imperfecta: an example of Astley-Kendall dysplasia. Further
delineation of a rare genetic disorder.
AB - An unusual osteochondrodysplasia presenting with lethal neonatal short limbed
dwarfism, defective ossification, and punctate calcification within cartilage is
presented. The features resemble four cases previously described with Astley
Kendall dysplasia.
PMID- 9643295
TI - Oto-onycho-peroneal syndrome: confirmation of a syndrome.
AB - We report two sibs with a similar syndrome of abnormal external ears, peculiar
facial features, nail hypoplasia, a bilateral fibrous fusion of the outer third
of the clavicle and the scapular spine, and the absence of a normal
acromioclavicular joint. The present patients represent the fourth and fifth
cases of the oto-onycho-peroneal syndrome (MIM 259780).
PMID- 9643296
TI - The diagnosis of Liddle syndrome by identification of a mutation in the beta
subunit of the epithelial sodium channel.
AB - Hypertension is a common multifactorial disorder associated with considerable
morbidity and mortality. The kidney plays a major role in the long term
regulation of blood pressure. Liddle syndrome (pseudo-hyperaldosteronism) is one
of a number of monogenic disorders of salt and water transport. In a kindred with
at least four affected members suffering from Liddle syndrome, we confirmed by
direct DNA sequencing the identity of a novel heterozygous mutation in h
betaENaC, the gene encoding the beta subunit of the amiloride sensitive
epithelial sodium channel which is expressed in the distal nephron. Single
stranded conformational polymorphism analysis showed cosegregation of the mutant
allele within the kindred with the Liddle phenotype. An insertion of an
additional cytosine into a string of six located between codons 593 and 595
results in a sequence frameshift and is predicted to produce a protein truncated
by 34 amino acids. The availability of a molecular diagnostic tool has
implications for the management of hypertension and genetic counselling in
families with Liddle syndrome.
PMID- 9643297
TI - New lethal disease involving type I and III collagen defect resembling geroderma
osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV.
AB - We describe the clinical findings and biochemical features of a male child
suffering from a so far undescribed lethal connective tissue disorder
characterised by extreme hypermobility of the joints, lax skin, cataracts, severe
growth retardation, and insufficient production of type I and type III
procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy
syndrome, and geroderma osteodysplastica, as these disorders show some symptoms
and signs shared with our patient. The child died because of failure of the
connective tissue structures joining the skull and the spine, leading to
progressive spinal stenosis. The aortic valve was translucent and insufficient.
The clinical symptoms and signs, together with histological findings, suggested a
collagen defect. Studies on both skin fibroblast cultures and the patient's serum
showed reduced synthesis of collagen types I and III at the protein and RNA
levels. The sizes of the mRNAs and newly synthesised proteins were normal,
excluding gross structural abnormalities. These findings are not in accordance
with any other collagen defect characterised so far.
PMID- 9643299
TI - Laws regarding insurance companies.
PMID- 9643298
TI - Three patients with a 45,X/46,X,psu dic(Xp) karyotype.
AB - Few cases of isochromosomes for the short arm of the X have been reported and all
are dicentric with variable portions of the long arms interposed between the two
centromeres. This paper reports three cases of complete short arm duplication of
one X chromosome in unrelated female patients. All patients also have a 45,X cell
line and present with some characteristic features of Turner syndrome. We used
conventional cytogenetics, in situ hybridisation, and molecular genetics to
describe all three structurally abnormal chromosomes and the parental origin of
two of them. We briefly discuss the "inactivation enhancement" theory; however,
any genotype-phenotype correlation is complicated by the presence of the 45,X
cell line.
PMID- 9643300
TI - Microsatellite markers for the cone-rod retinal dystrophy gene, CRX, on 19q13.3.
PMID- 9643301
TI - Neonatal hearing screening: a step towards better services for children and
families.
PMID- 9643302
TI - Categories of auditory performance: inter-user reliability.
AB - Categories of Auditory Performance (CAP) describes a scale used to rate outcomes
from paediatric cochlear implantation in everyday life. It differs from more
technical measures by being readily applied and easily understood by non
specialist professionals and by parents. Being based on subjective assessments,
there is a need to establish whether ratings by different persons are comparable.
Therefore, an analysis of inter-user reliability was undertaken using ratings
from 23 children followed up at various intervals after implantation. Analysis
relating scores by local teachers of the deaf and the teachers of the deaf at the
implant centre revealed very high inter-user reliability (correlation coefficient
0.97). This result establishes the reliability of CAP as an outcome measure for
use in cochlear implant programmes.
PMID- 9643303
TI - Otitis media with effusion and size at birth.
AB - To investigate whether recurrent or persistent otitis media with effusion (OME)
was associated with particular patterns of fetal growth, we conducted a case
control study of 129 children admitted for insertion of grommets and 150
controls. The risk of OME was not statistically significantly related to
gestational age or individual measures of size at birth, but the ratio of head
circumference to total length and the ponderal index at birth were statistically
significantly lower in children with OME, both before and after adjustment for
the potentially confounding effects of sex, age at current operation, and
maternal gravidity. Mothers of cases were 2.2 times more likely than those of
controls to have had one or more previous pregnancies that had not ended in a
live birth (95% CI 1.3-3.8). We conclude that fetal growth, reflected by
proportions at birth, may affect later risk of recurrent and persistent OME.
PMID- 9643304
TI - Avoidable late diagnosis of significant sensorineural hearing loss: implications
for practice.
AB - The records for all children from a five-year birth cohort in the geographically
defined area of Lothian who were referred by their health visitor to a
centralized second tier audiology service after they failed their 7-9 month
infant distraction hearing screen were reviewed. The sensitivities,
specificities, positive predictive values and yield of this screen for the
detection of significant sensorineural hearing loss > or =40 dBA requiring aiding
and for a conductive loss persisting beyond one month over 30 dBA were
determined. In addition, the records were studied for the same five-year birth
cohort for children presenting to the centralized multidisciplinary third tier
clinic with a significant sensorineural hearing loss requiring aiding, and the
reasons for late diagnosis were determined. If high risk neonatal screening had
been available for this population then potentially 67.5% (27 out of 40) of cases
could have been identified by an appropriate age. Elimination of health visitor
distraction screen false negatives for cases with loses over 60 dBA would
potentially increase the case identification by the appropriate age to 45% (1 8
out of 40). Thus, there is greater scope for improving our present results with
the introduction of high risk neonatal screening than by improvements in the
health visitor screen.
PMID- 9643305
TI - Maternal anxiety and attitudes to universal neonatal hearing screening.
AB - Neonatal hearing screening of all babies within the maternity unit is now
feasible using transient evoked otoacoustic emission (TEOAE) recording. However,
in many maternity units in the United Kingdom, the majority of babies are
discharged within the first 48 hours. During the first two days of life, there is
a higher proportion of babies in whom emissions cannot be recorded. A universal
TEOAE hearing screen has been implemented in Whipps Cross Hospital. As 70% of the
babies are discharged from the maternity unit before they are 48 hours old, a two
stage screen was implemented, with failure at the initial TEOAE test being
followed by a retest after 4-6 weeks. The maternal anxiety caused by this model
was investigated in 288 mothers enrolled for the initial TEOAE test. Generally,
anxiety was low and attitudes towards the screen were positive. Ninety-seven per
cent of mothers considered the screen to be worthwhile at the initial test with
15% feeling it had caused some anxiety but less than 1% being very worried. The
mothers who had some anxieties were not dissatisfied with the screen, and within
this group there was no increase in the proportion of babies who had failed the
initial test. At the retest, two of 57 mothers (3.5%) considered they were very
worried, but there was no significant deterioration in attitude towards the
screen. Spielberger's State-Trait Anxiety Inventory revealed no significant
difference in the anxiety state of the retest group when compared with a control
group whose babies had not received a neonatal hearing test. The results of the
initial test and the retest did not influence the anxiety state of the mothers.
Ways of minimizing anxiety caused to a minority of mothers whilst maintaining
positive attitudes to the screen are discussed.
PMID- 9643306
TI - Evaluating noise induced hearing loss with distortion product otoacoustic
emissions.
AB - This study assessed the clinical efficacy of screening for noise induced hearing
loss (NIHL) with distortion product otoacoustic emissions (DPOAE). DPOAEs were
recorded from 76 military personnel (137 ears) aged between 17 and 41 years in
response to equilevel 70 dB SPL primary stimulating tones. The 2f1-f2 DPOAE
levels were correlated with audiometric thresholds at frequencies close to f2.
Ears with normal audiograms, but with a history of military noise exposure, had
DPOAEs that were significantly decreased in amplitude as compared to the ears of
normal hearing non-exposed to noise subjects. These ears also had an increased
absence of DPOAEs as compared with the ears of the normal hearing non-exposed to
noise subjects. Although, in general, the DPOAE amplitudes and spectral frequency
ranges reflected the audiometric NIHL configurations, in a number of cases DPOAEs
were present for hearing losses up to 75 dB HL. As a consequence, DPOAEs
correlated moderately and negatively with the audiometric thresholds. Applying
test criteria designed to logically reflect NIHL, DPOAE sensitivity and
specificity levels ranged between 0.51-0.90 and 0.63-0.25, respectively. These
findings indicate that DPOAEs, recorded and analysed as described, are not
sufficiently sensitive to serve as a single test to identify NIHL.
PMID- 9643307
TI - The effect of gentamicin and furosemide given in combination on cochlear
potentials in the guinea pig.
AB - Single doses of gentamicin and furosemide given in combination result in a rapid
and profound loss of cochlear function. In this study, measurement of three gross
cochlear potentials (cochlear microphonics, compound action potentials and the
endocochlear potential) were carried out in order to determine the ototoxic sites
of action of the drugs given in combination. The rapidity and severity of the
cochlear deficit is dose dependent and with the doses employed in this study (80
mg/kg gentamicin i.v. 80 mg/kg furosemide i.v.), complete loss of cochlear
function is seen after about 72 hours. Twenty-four hours after i.v.
administration of the drugs, significant increases in compound action potential
thresholds between 6 and 32 kHz were seen. In contrast, over this frequency range
the generation of cochlear microphonics in response to stimulus levels of 70 dB
SPL appeared to be unaffected. The endocochlear potential remained unaffected at
24 and 72 hours after administration. These findings are taken as evidence that
the primary site of ototoxic action of the two drugs in combination may be at the
level of the inner hair cells and/or the afferent synapse.
PMID- 9643308
TI - Feasibility of otoacoustic emissions as a hearing screen following grommet
insertion.
AB - Following grommet insertion, it is important to establish that there is no
underlying sensorineural hearing impairment. In this hospital, approximately 1000
grommet insertions are performed each year, thus generating a heavy workload of
review appointments for ENT and audiology. The present study investigates the
efficacy of performing evoked otoacoustic emissions screening on 108 children
when they were ready to leave the hospital following grommet insertion. Bilateral
normal otoacoustic emissions were recorded in 32% (35 children), although 99%
(105) of the 106 children attending the outpatient review appointment had normal
hearing sensitivity. If normal hearing thresholds were established immediately
following surgery, it can be argued that this obviates the need for an outpatient
review appointment; however, in this study only one-third of children could be
discharged after surgery. Otoacoustic emissions therefore does not represent an
effective screen at this stage.
PMID- 9643309
TI - Cytokines: clues to the pathogenesis of SLE.
PMID- 9643310
TI - Interleukin-2 and systemic lupus erythematosus--fifteen years later.
AB - Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder in which
multiple immunologic abnormalities have been described. In this review, we
thoroughly analyse the impaired T cell production of, and response to,
interleukin-2 (IL-2) characteristic of patients with SLE. Since it was first
reported, several articles have provided us with enlightening, but somewhat
confusing, data that reveal the complexity of the subject. The IL-2 production by
T cells is part of a complex network in which a discrete alteration is capable of
disrupting the whole system. On the other hand, regulatory mechanisms exist that,
in an attempt to compensate the primary alteration, provoke secondary defects.
Evidence indicates that this defect is not intrinsic, but rather, results from
multiple microenvironmental influences that act on the T cell and modify its
activation state and its cytokine production. Abnormalities in co-stimulatory
mechanisms and in cytokines that may be related to the IL-2 production
deficiency, have been described in patients with SLE. We also consider the
information derived from murine SLE models, IL-2 knockout models and reports
concerning the immune dysregulation present in patients with SLE.
PMID- 9643311
TI - DNAse treatment does not improve the survival of lupus prone (NZB x NZW)F1 mice.
AB - OBJECTIVE: To examine the efficacy of deoxyribonuclease I (DNAse) therapy in the
(NZB x NZW)F1 murine model of lupus. METHODS: Lupus-prone female (NZB x NZW)F1
mice were treated daily with 0-15 microg/g of recombinant DNAse for 1-6 months.
Parameters including anti-DNA autoantibody production, activation of cytokine
secreting cells, kidney function and longevity were monitored. RESULTS: DNAse
treatment selectively reduced the number of B cells secreting anti-dsDNA
antibodies for approximately one month. However, neither short-term nor long-term
treatment altered cytokine production, delayed the onset or reduced the severity
of glomerulonephritis, or prolonged survival. CONCLUSION: DNAse treatment
initiated before, during, or after the onset of murine lupus did not improve
clinical outcome.
PMID- 9643312
TI - Systemic lupus erythematosus VII: frequency and impact of secondary Sjogren's
syndrome.
AB - BACKGROUND: The prognosis of patients with systemic lupus erythematosus (SLE)
largely depends on the severity of cumulative organ damage during the course of
the disease. While Sjogren's syndrome (SS) predominantly affects exocrine glands,
a considerable number of patients develop visceral organ damage. Thus, the
occurrence of a secondary SS (2(o)SS) in SLE patients, may result in more
extensive organ damage and thereby adversely affect prognosis. PATIENTS/METHODS:
138 patients meeting the 1982 American College of Rheumatology (ACR)
classification criteria for SLE were prospectively studied over a mean period of
ninety months. 2(o)SS was diagnosed according to the 1993 European Study Group
criteria and complication rates and prognosis were compared between patients with
and without SS. RESULTS: 27 patients (19%) developed SS after a mean period of 48
months. There was a gradual increase in SS prevalence over time after SLE-onset.
2(o)SS patients were older (mean age 41 vs 35 years, P = 0.03), had less renal
disease (19% vs 38%, P = 0.04), more thrombocytopenia (26% vs 9%, P = 0.05) and
similar serological profiles (including anti-SSa) as patients without SS. Overall
mortality was lower in patients with SS (4% vs 13.5%, P = 0.01), while lifetable
analysis showed improved survival estimates for 2 SS patients with borderline
statistical significance (P = 0.06). CONCLUSIONS: 2(o)SS develops in about one
fifth of SLE patients in a time-dependent fashion: these patients are older, have
less renal involvement and their prognosis is at least as good as for those
remaining free of SS.
PMID- 9643313
TI - About systemic lupus erythematosus and thrombotic thrombocytopenic purpura.
PMID- 9643314
TI - Polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome.
AB - Polyarteritis nodosa (PAN), first described by Kussmaul and Maier, is a well
known form of necrotizing angiitis whose manifestations are weight loss, fever,
asthenia, peripheral neuropathy, renal involvement, musculoskeletal and cutaneous
manifestations, hypertension, gastrointestinal tract involvement, and cardiac
failure. Recently individualized from PAN, microscopic polyangiitis (MPA) is a
systemic vasculitis of small-size vessels whose clinical manifestations are very
similar to those of PAN, but it is characterized by the presence of rapidly
progressive glomerulonephritis (RPGN), which is nearly constant, and pulmonary
involvement usually absent in PAN. Churg Strauss syndrome (CSS) is a disorder
characterized by hypereosinophilia and systemic vasculitis similar to that of PAN
and occurring in individuals with asthma and allergic rhinitis. Considering the
etiologies of PAN, primary and secondary vasculitides can also be distinguished
because PAN can be the consequence of hepatitis B virus (HBV) infection and
sometimes of other etiologic agents. The prognosis of systemic vasculitides has
been transformed by corticosteroids that are, except in HBV-related PAN, the
basic treatment. Immunosuppressive drugs, especially cyclophophamide, have also
contributed to improving the prognosis, but their precise role in the management
of these vasculitides is still being elucidated.
PMID- 9643315
TI - Childhood vasculitis.
AB - Vasculitis can and does occur in childhood. Apart from the relatively common
vasculitides (Henoch-Schonlein purpura, Kawasaki disease and in world wide terms
Takayasu disease) there are a number of important but comparatively rare
disorders affecting children. These include macroscopic and microscopic
polyarteritis, cutaneous polyarteritis, Wegener's granulomatosis, Churg-Strauss
syndrome, primary angiitis of the central nervous system, hypersensitivity
angiitis, hypocomplimentaemic urticarial vasculitis, vasculitis associated with
various connective tissue disorders and vasculitis associated with conditions
such as Behcets syndrome, familial Mediterranean fever and Cogan's syndrome.
Distinguishing these conditions from other disorders is often difficult and
requires clinical acumen and appropriate investigative procedures. With modern
therapeutic agents, it is possible to implement appropriate therapy but in spite
of this, there remains a not inconsequential morbidity and mortality.
PMID- 9643316
TI - Giant cell arteritis.
AB - In many populations giant cell arteritis (GCA) is the most common form of
vasculitis. Genetic markers, ethnic factors, and increasing age over 50 years
appear to enhance susceptibility and an infection may trigger its onset. Recent
investigations provide evidence that the vasculitic reaction is part of an immune
response to an antigen residing in involved artery walls. These studies along
with the description of an experimental model of the disease have significantly
increased out understanding of GCA.
PMID- 9643317
TI - Vasculitis in systemic lupus erythematosus.
AB - Vasculitis frequently complicates SLE, is associated with significant morbidity
and mortality, and its pathophysiology is poorly understood. In seriously ill
lupus patients with vasculitis, immunosuppression should almost always be
considered.
PMID- 9643318
TI - Mixed cryoglobulinaemia: a cross-road between autoimmune and lymphoproliferative
disorders.
AB - Mixed cryoglobulinaemia (MC) is a systemic vasculitis, secondary to the
deposition in small and medium-sized blood vessels of circulating immune
complexes, mainly the cryoglobulins, and complement. MC is characterised by a
typical clinical triad (purpura, weakness, arthralgias) and by one or more organ
involvement: chronic hepatitis, glomerulonephritis, peripheral neuropathy, skin
ulcers and diffuse vasculitis. In a limited number of MC patients, a malignancy,
that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also
develop. Hepatitis C virus (HCV) infection has been found in the majority of
patients with MC; the frequency of HCV markers (91%) was significantly higher
than other rheumatic diseases (6.4%), namely systemic lupus, Sjogren's syndrome,
rheumatoid arthritis and systemic sclerosis, or healthy controls (1.2%). The HCV
infection of lymphoid tissues may represent the remote event leading to B
lymphocyte proliferation responsible for autoantibodies and immune-complex
production. In a similar way, HCV infection may also be involved in the
pathogenesis of other autoimmune (glomerulonephritis, thyroiditis, lung fibrosis,
autoimmune hepatitis, porphyria cutanea tarda) and lymphoproliferative disorders
(monoclonal gammopathies, B-cell lymphomas). MC shares numerous clinico
serological and pathological features with the above disorders. HCV seems to be
their common etiological agent; however, a variable combination of unknown co
factors (infectious, genetic, environmental) should be determinant for the
appearance of different clinical patterns.
PMID- 9643319
TI - Pathogenesis of vasculitis.
AB - This review discusses current thoughts on the pathogenesis of vasculitis.
Secondary vasculitides, frequently associated with infections or systemic
autoimmune diseases, are, in most cases, characterized by immune deposits in the
vessel wall, which probably underlies the development of lesions. In the primary
vasculitides, immune deposits are generally absent. A group of primary
vasculitides is, however, strongly associated with anti-neutrophil cytoplasmic
autoantibodies (ANCA). Various in vitro and in vivo experimental data suggest
that those ANCA are involved in the pathogenesis of lesions in the associated
disorders.
PMID- 9643320
TI - Wegener's granulomatosis: disease course, assessment of activity and extent and
treatment.
AB - Wegener's granulomatosis (WG) belongs to the group of necrotizing primary
systemic vasculitides of unknown etiology, that are associated with anti
neutrophil cytoplasmic antibodies. The pathological hallmark of WG is the
coexistence of vasculitis and granuloma. Due to more sensitive diagnostic
instruments, especially ANCA testing, the incidence of diagnosis of WG has risen
in the past ten years. Although the precise pathophysiology is not understood
yet, there is ample evidence that ANCA, which can lead to cytotoxic reactions in
the vascular texture, play a major role, possibly promoted by a dysbalance in the
anti-idiotypic network. The clinical disease course is typically two-phasic,
beginning with a granulomatous inflammation of the upper respiratory tract, that
usually is followed by a generalized vasculitic phase, that can range from mild
organ dysfuntion to life threatening multi-organ failure. Consequently,
diagnostic procedures, patients' assessment and therapeutic regimens need to be
individualized, adapted to stage and activity of the disease as well as
standardized.
PMID- 9643321
TI - Neuropeptides: role in inflammatory skin diseases.
AB - The cutaneous nervous system recently has been demonstrated to interact with
multiple target cells in the skin and to mediate actions important in
inflammatory conditions. Neuropeptides released by cutaneous neurons such as
substance P (SP), vasointenstinal peptide (VIP), calcitonine gene regulated
peptide (CGRP), proopiomelancortin (POMC) peptides and others modulate the
function of immunocompetent and inflammatory cells as well as epithelial and
endothelial cells. They have been found to function as mediators of cell
proliferation, cytokine and growth factor production as well as adhesion molecule
and cell surface receptor expression. In addition many cells including
keratinocytes, fibroblasts, endothelial cells and inflammatory cells have been
shown to release several neuropeptides and they express their corresponding
receptors. These findings indicate that neuropeptides participate in the complex
network of mediators that regulate cutaneous inflammation, hyperproliferation and
wound healing.
PMID- 9643322
TI - Leishmaniasis and the JEADV.
PMID- 9643323
TI - American cutaneous leishmaniasis due to Leishmania (Viannia) guyanensis as an
initial clinical presentation of human immunodeficiency virus infection.
AB - The authors present the first report of Leishmania (Viannia) guyanensis (L.(V.)
guyanenesis) associated with human immunodeficiency virus (HIV) in a Brazilian
heterosexual man. It is also the first case of HIV infection associated with
American cutaneous leishmaniasis in Brazilian Western Amazonia. The patient had
cutaneous and mucous lesions with a negative Montenegro skin test. Histopathology
showed large numbers of amastigotes, even in a lesion which had clinically
healed. L.(V.) guyanenesis was typed by an immunoenzymatic technique. Various
therapies were attempted, but the patient relapsed after each episode of
treatment.
PMID- 9643324
TI - American cutaneous leishmaniasis associated with HIV infection: report of four
cases.
AB - OBJECTIVE: A report of four cases of American cutaneous leishmaniasis associated
with HIV infection is presented. BACKGROUND: The association of mucocutaneous
leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the
literature thus far. SUBJECTS: Four new cases are described and the differences
between the clinical presentation in immunocompromised and immunocompetent
patients are emphasized. CONCLUSIONS: Multiple cutaneous lesions plus mucosal
involvement characterize the clinical presentation of American cutaneous
leishmaniasis in association with HIV infection in the majority of the cases. A
serological investigation for HIV infection is recommended for patients
presenting with this type of clinical picture, especially if the patient is a
young male.
PMID- 9643325
TI - Leishmaniasis of glans penis.
AB - BACKGROUND: Leishmaniasis is an important protozoan disease. In the Americas it
is produced by several species of the genus Leishmania, transmitted by sand flies
of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more
serious involvement of oronasal mucosa that may progress to destruction of
central structures of the face and to the life-threatening visceral forms.
Leishmania Viannia braziliensis is the most widespread species in Brazil and is
often associated with mucosal involvement. Cutaneous lesions are commonly
localised in uncovered areas of the body. Genital lesions are rare. MATERIALS AND
METHODS: A patient with an ulcerated lesion of the glans penis, followed
subsequently by mucosal lesions of the nasal cavity and palate, is presented.
Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy
of the ulcer border processed for histopathological examination and culture in
NNN medium. RESULTS: Leishmanin skin test was positive. Histopathology showed a
granulomatous infiltrate containing some parasites. Culture was positive for
Leishmania sp., and was later identified by zymodeme analysis and monoclonal
antibodies as L.(V.) braziliensis. The patient was treated with pentavalent
antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed.
COMMENTS AND CONCLUSIONS: In men, especially over 50 years of age, ulceration of
the glans penis is highly suggestive of carcinoma. Precise differential diagnosis
is imperative. A lesion, such as the one reported, may cause diagnostic
difficulties when it presents in countries different from the source, where the
condition is very uncommon. This is increasingly frequent in the current era of
widespread air travel.
PMID- 9643326
TI - Generalized cutaneous leishmaniasis in acquired immunodeficiency syndrome.
AB - BACKGROUND: Leishmaniasis associated with HIV/AIDS has been reported in the last
decade. CASE REPORT: A case of generalized cutaneous leishmaniasis in a patient
with AIDS is described. The case is paradoxical in that the cutaneous lesions
resemble anergic leishmaniasis caused by Leishmania (L.) amazonensis and Jorge
Lobo's disease, but the positive Montenegro test and the clinical improvement
with antimonial are more commonly observed in leishmaniasis caused by L.(V.)
braziliensis. COMMENT: The immunosuppression due to HIV/AIDS seen in this patient
may explain the dissemination of the lesions, but the positive specific response
to leishmanial antigen may explain the good response to the antimonial treatment.
PMID- 9643327
TI - Prevalence of bands other than 160 and 130 kDa in pemphigus sera (a multicenter
immunoblotting study). Gruppo Italiano Studi Epidemiologici in Dermatologia
(GISED).
AB - Patients with pemphigus may produce antibodies against molecules other than the
classical transmembranal ones. Recently, for example antibodies to 230 kDa
antigens have been found in association with antibodies to intercellular
substance. To better understand their prevalence, clinical correlates and
prognostic significance of bands other than 130 and 160 kDa, we studied 67
pemphigus sera. About one-fourth of patients revealed multiple heterogeneous
bands and 13% the 230 kDa band. When challenged with the recombinant protein
rBP55, the carbossiterminal portion of bullous pemphigoid major antigen, all 230
kDa-positive-sera proved negative. Caution is to be recommended in interpreting
pemphigus sera with a band migrating at the 230 kDa level.
PMID- 9643328
TI - Anaerobic bacteria in men with urethritis.
AB - AIM: Investigation of the urethral flora in men with urethritis, with particular
reference to anaerobic bacteria. METHODS: Multiple cultures were performed on
three urethral samples from 110 men attending the STD Clinic of the School of
Medicine in Seville: 35 with no evidence of urethritis (control group), and 75
with urethritis (17 gonococcal urethritis (GU) and 58 non-gonococcal urethritis
(NGU)). In the 58 men with NGU, Chlamydia trachomatis was isolated in 16 (27.5%),
Ureaplasma urealyticum in 18 (31%), Trichomonas vaginalis in two (3.4%) and no
pathogens were isolated in the remaining 22 (38%) patients. RESULTS: Aerobic
flora, mainly Staphylococcus spp., were isolated less frequently (41%) in
patients with GU than in the control group (80%), and those with NGU (72%).
Anaerobic flora were isolated in 62% of patients, with similar isolation rates in
each group. Gram-negative anaerobes were more frequently isolated in men with
urethritis, especially NGU, compared to controls (P < 0.05). Prevotella spp. and
Bacteroides spp. were significantly more frequently isolated in patients with
NGU, including Chlamydia-negative NGU. Fusobacterium spp. were more frequent in
the Chlamydia-positive NGU than in the controls (P < 0.05). P. magnus was the
most frequent anaerobic species found in the control group, while P. prevotii was
most frequently seen in the urethritis group. B. ureolyticus, P. prevotii and P.
tetradius were more frequent on the NGU group (P < 0.05). B. ureolyticus was
commoner in patients with Chlamydia-negative NGU, while P. tetradius and P.
asaccharolytica was commoner in those where C. trachomatis was isolated than in
the control group. CONCLUSION: Urethral microflora isolated showed ten bacterial
genus and 25 different species of anaerobes. The spectrum of these microflora
changed with the presence of urethritis and varied with its aetiology.
PMID- 9643329
TI - 'Suction split' as a routine method to differentiate epidermolysis bullosa
acquisita from bullous pemphigoid.
AB - BACKGROUND AND DESIGN: Epidermolysis bullosa acquisita (EBA) and bullous
pemphigoid (BP) are diseases with similar clinical, histological, and
immunofluorescent findings. Diagnosis requires the use of immunoelectron
microscopy, immunoprecipitation or immunoblotting, but in recent years the
differential diagnosis has been based on a cheaper technique named salt split
skin. This study demonstrates that with a suction blister the fracture is at the
same level as that obtained with the sodium split method and that it is also
faster and cheaper. Suction blisters on normal skin and autoimmune perilesional
bullous lesions, obtained with a hand vacuum pump, were studied by direct
immunofluorescence and electron microscopy to evaluate the level of the split on
normal suction split skin. Normal human split skin was also used as a substrate
for an indirect immunofluorescent study using sera of patients with BP (68 sera),
EBA (10 sera) and cicatricial pemphigoid (CP) (16 sera). Direct immunofluorescent
examination was also done on perilesional skin after artificial separation
obtained with a hand-vacuum pump in patients with the same diseases listed above
(32 BP, 11 CP, 6 EBA). RESULTS: On normal human skin split by suction or sodium
chloride (NaCl; 1 mol/l) direct immunofluorescence and electron microscopy
demonstrated that the split is at the lamina lucida level. Indirect
immunofluorescent study of both normal human skin and perilesional skin split
using suction as a substrate showed IgG deposits localized on the floor of the
suction blister in all cases of EBA, whereas in over 88% of cases of BP and in
over 62% of CP the IgG were localized on the roof. Similar results were obtained
with direct immunofluorescence in perilesional skin. CONCLUSIONS: 'Suction split'
represents a simple technique to differentiate EBA from BP. This method provides
final response in a few hours compared to at least 1-2 days with the sodium split
method. Furthermore, the suction split method is cheaper and the tissue can be re
utilized for molecular biology and immunohistochemical studies.
PMID- 9643330
TI - A case of coumarin necrosis with penile and pedal involvement.
AB - A 57-year-old male patient with advanced adenocarcinoma of the lung, who was
administered oral anticoagulant therapy because of pulmonary embolism, developed
coumarin necrosis confined to the penis and feet. To our knowledge, this patient
showing acral involvement is the seventh case of coumarin-induced penile necrosis
reported to date.
PMID- 9643331
TI - Mycosis fungoides with involvement of the oral cavity.
AB - Mycosis fungoides rarely involves the oral cavity. To our knowledge only 29 cases
of oral cutaneous T-cell lymphoma have been described up to 1994. This report
presents a case of mycosis fungoides with involvement of the oral cavity in a 57
year-old man who died from septicemia 7 months after the onset of oral
involvement.
PMID- 9643332
TI - Idiopathic plantar hidradenitis.
AB - We describe four cases of idiopathic plantar hidradenitis (IPH), a form of
neutrophilic eccrine hidradenitis (NEH) localized on the feet of otherwise
healthy young persons. Our patients were all males, 8-17 years old, in apparently
good health, but presenting erythematous painful papules, plaques and nodules on
the soles. They were afebrile and there were no constitutional symptoms. The
differential diagnoses included erythema nodosum, vasculitis and traumatic
plantar urticaria. The histological features of IPH are similar to those of NEH,
except for the absence of syringosquamous metaplasia. The patients were treated
with topical steroids and oral NSAID, with total resolution of the lesions in 1
or 2 weeks.
PMID- 9643333
TI - Palmar spiny keratoderma associated with type IV hyperlipoproteinemia.
AB - We report the case of a 35-year-old man with acquired palmar spiny keratoderma
(SK) in association with type IV hyperlipoproteinemia. Cutaneous lesions appeared
11 years before with no history of any previous skin conditions, topical
medication or systemic treatment with Vitamin A-derived drugs, x-irradiation,
arsenic poisoning or prolonged sun exposure. Family aggregation for SK or other
disorders of keratinization was ruled out. Blood chemistries demonstrated
hypertriglyceridemia (422 mg/dl) and elevation in plasma concentration of the pre
beta fraction (VLDL) of lipoproteins pattern compatible with a type IV
hyperlipoproteinemia. Family aggregation for this metabolic defect was then
confirmed. The histologic hallmark of the 'spine' lesion was a compact column of
hyperparakeratotic cells (columnar hyperparakeratosis) continuous with a
hypogranular layer, without further evidence of dyskeratotic or vacuolated
keratinocytes and inflammatory cells in the corresponding dermis. SK represents a
well-definite entity which fulfills precise clinico-histologic criteria. However,
three main questions are related to SK: differential diagnosis with porokeratosis
on histologic examination (columnar hyperparakeratosis or hyperorthokeratosis
alone in SK vs. cornoid lamella accompanied by remarkable dermoepidermal changes
in porokeratosis); classificative scheme (proper nomenclature to avoid misleading
and confounding names); and nosological arrangement (probably two subsets exist:
hereditary or benign; and acquired, or idiopathic, which may be paraneoplastic in
about 50% of the patients). To the best of our knowledge this is the first case
reporting the association between SK and a metabolic impairment although the real
connections linking these conditions are still unclear.
PMID- 9643334
TI - Fatal cytophagic histiocytic panniculitis after a short response to cyclosporine.
AB - Cytophagic histiocytic panniculitis (CHP) is a disorder characterized by a
histiocytic infiltrate in the subcutaneous adipose tissue which often extends to
involve systemic organs. Fever, pancytopenia, hepatosplenomegaly, mucosal ulcers
and serositis are common systemic symptoms. Although remissions have been
reported, the disease tends to follow a chronic course often complicated by
terminal hemorrhagic diathesis and death. Several reports in the recent
literature have suggested that cyclosporine is the treatment of choice in CHP. We
report the first case of cyclosporine treatment failure in CPH. Despite an
initial response to treatment and persistent resolution of cutaneous lesions, the
internal disease progressed resulting in the patient's death. Therefore the
evolution of skin lesions and signs of systemic involvement may not be an
accurate assessment of disease activity in patients with CHP being treated with
cyclosporine.
PMID- 9643335
TI - Verrucoid cutaneous rhinosporidiosis.
AB - Verruca vulgaris like lesions of cutaneous rhinosporidiosis are reported in a
middle aged Indian male. He also had nasal rhinosporidiosis. Imprint smears from
skin lesions showed sporangia with endospores, confirming the diagnosis.
PMID- 9643336
TI - Cutaneous larva migrans associated with water shoe use.
AB - It has been long suspected that footwear is protective against cutaneous larva
migrans. This case report describes a woman who developed cutaneous larva migrans
despite wearing 'protective' footwear. We forward a hypothesis by which recently
popular water shoes may actually be conducive to the development of cutaneous
larva migrans rather than having a protective function.
PMID- 9643337
TI - Cytarabine-induced acral erythema: a localized form of toxic epidermal
necrolysis?
PMID- 9643338
TI - Human papilloma virus infection in the oral cavity--a source of infection.
PMID- 9643339
TI - Calciphylaxis in chronic renal failure.
PMID- 9643340
TI - A probable role of an infectious agent in polymyositis associated with antibodies
against histidyl-tRNA synthetase: antisynthetase syndrome.
PMID- 9643341
TI - Lymphomatoid papulosis and progression to T-cell immunoblastic lymphoma.
PMID- 9643342
TI - Acne due to amineptine abuse.
PMID- 9643343
TI - PUVA therapy in localized scleroderma.
PMID- 9643344
TI - Reduction of phosphatidylcholine hydroperoxide by apolipoprotein A-I:
purification of the hydroperoxide-reducing proteins from human blood plasma.
AB - Plasma glutathione peroxidase (GSHPx) has been suggested to reduce submicromolar
levels of free fatty acid hydroperoxides and phosphatidylcholine hydroperoxides
(PC-OOH), and therefore these hydroperoxides are undetectable in human blood
plasma. The capacity for the reduction should be about 2.5 microM as the level of
glutathione in human plasma is about 5 microM. However, 2 h of aerobic incubation
of 58 microM PC-OOH in human plasma at 37 degrees C resulted in the formation of
36 microM phosphatidylcholine hydroxide (PC-OH). The presence of PC-OOH-reducing
protein other than plasma GSHPx was suggested by the results. a) The same rates
of PC-OOH decay and PC-OH formation were observed in both sera from rats with
selenium-deficient and selenium-supplemented diet; b) the PC-OOH-reducing
activity was observed only in the high molecular weight fraction but not in the
low molecular weight fraction; and c) albumin did not work as a reducing
substrate of plasma GSHPx. We have isolated two hydroperoxide-reducing protein
fractions from human plasma by a sequential purification scheme, comprising an
ammonium sulfate precipitation followed by sequential chromatography on anion
exchange, hydrophobic interaction, and heparin columns. One of the proteins was
identified as apolipoprotein A-I by N-terminal amino acid sequence analysis.
Moreover, the hydroperoxide-reducing activity of one of the fractions was
inhibited almost completely by the addition of anti-apolipoprotein A-I antibody.
These findings demonstrate that apolipoprotein A-I in high density lipoprotein
can reduce PC-OOH to PC-OH.
PMID- 9643345
TI - Effects of heterozygous lipoprotein lipase deficiency on diet-induced
atherosclerosis in mice.
AB - Heterozygous lipoprotein lipase deficiency (LPL+/-) is common and has been
implicated in premature atherosclerosis in epidemiologic studies. However, in
vitro data suggest that LPL deficiency in the vascular wall may be
antiatherogenic. To address the role of LPL in atherosclerosis, LPL+/- mice in
the C57BL/6J background were fed an atherogenic diet for 8 months. LPL+/- mice
were more dyslipidemic than +/+ animals due to increased concentrations of non
HDL lipoproteins. There was no difference in aortic origin atherosclerosis
between LPL+/- (n=56) and +/+ (n=55) mice. LPL+/- mice in the low density
lipoprotein receptor knockout (LDLR-/-) background were fed the same atherogenic
diet for 3 months. LPL+/-LDLR-/- mice were more dyslipidemic than LPL+/+LDLR-/-
animals. There was no difference in atherosclerosis assayed for the entire aorta
and no difference in aortic sterol content between LPL+/-LDLR-/- (n=28) and
LPL+/+LDLR-/- (n=15) mice. LPL protein was detected in murine lesions in a
consistent layered pattern. More luminal, lipid-laden macrophages generally did
not stain for LPL, but deeper, lipid-poor macrophages as well as necrotic core
regions contained immunoreactive LPL. LPL protein was more abundant in lesions
from LPL+/+ LDLR-/- than LPL+/-LDLR-/- mice. After eating an atherogenic diet,
LPL+/- as compared to LPL+/+ mice have more dyslipidemia, but no more
atherosclerosis, and less LPL protein in atherosclerotic lesions. These data
suggest that lipoprotein lipase deficiency in the vascular wall could prevent the
retention of atherogenic lipoproteins.
PMID- 9643346
TI - Synthesis and accumulation of a receptor regulatory protein associated with lipid
droplet accumulation in 3T3-L1 cells.
AB - Synthesis and accumulation of the recently identified prostaglandin F2alpha
receptor regulatory protein (FPRP) was found to correlate closely with lipid
droplet accumulation by 3T3-L1 preadipose cells. FPRP, a transmembrane
glycoprotein, has been shown to regulate the binding of ligand to certain seven
transmembrane receptors. Anti-FPRP immunohistochemistry, Western blotting, and
metabolic labeling/immunoprecipitation experiments demonstrated that FPRP was not
detectable in undifferentiated 3T3-L1 cells. Interestingly, low levels of FPRP
mRNA were detected in the undifferentiated 3T3-L1 cells. After induction of
adipose differentiation, FPRP mRNA increased approximately 3 fold whereas FPRP
synthesis increased approximately 50 fold. Differentiation induction with either
dexamethasone/insulin/isobutylmethylxanthine or the thiazolidinedione derivative
ADD 4743 were both effective at inducing FPRP accumulation and accumulation of
lipid droplets. By co-immunohistochemical and lipid staining, greater than 99% of
the cells accumulating lipid droplets possessed FPRP. FPRP mRNA and protein are
also found in rat adipose tissue. Treatment of 3T3-L1 cells with an FPRP anti
sense oligonucleotide during differentiation decreased FPRP accumulation and
resulted in a decrease in lipid droplets without altering the level of induction
of a late marker of adipocyte differentiation, glycerol-3-phosphate dehydrogenase
activity. Transient expression of an FPRP cDNA in undifferentiated 3T3-L1 cells
was insufficient to induce lipid droplet accumulation.
PMID- 9643347
TI - Analysis of particle size and lipid composition as determinants of the metabolic
clearance of human high density lipoproteins in a rabbit model.
AB - Hypertriglyceridemia is commonly associated with triglyceride (TG) enrichment of
high density lipoprotein (HDL) and reduction in HDL cholesterol and
apolipoprotein A-I levels. We have recently reported that lipolytic modification
of TG-rich HDL, which reduces particle size, enhances its clearance from the
circulation. In the present study, we examined the role of particle size and
lipid composition in determining the metabolic clearance of human HDL, in the
absence of substantial in vivo modification of the particle by hepatic lipase.
The rabbit, which has a very low hepatic lipase activity, was used for this
purpose. Plasma fractions d < 1.21 g/ml were first isolated by
ultracentrifugation from fasting humans with normal (NTG, n=6, mean plasma TG
concentration=1.26+/-0.21 (SEM) mmol/l) or elevated plasma TG levels (HTG, n=5,
TG=4.49+/-0.65 mmol/l). Small and large HDL particles were separated by gel
filtration chromatography and were labeled with either 125I or (131)I. Large HDL
were cleared more rapidly than small HDL in 10 out of 11 studies (P=0.006). There
was, however, no difference in the fractional catabolic rate (FCR) of large HDL
isolated from NTG versus from HTG subjects or in the FCR of small HDL from NTG
versus HTG individuals. There was also no correlation between the TG content of
HDL and its FCR. In summary, large, lipid-rich human high density lipoproteins
(HDL) are cleared more rapidly than small human HDL in rabbits. These results,
combined with our previous observation, also support the hypothesis that
triglyceride enrichment of HDL, in the absence of substantial lipolytic
modification, is not sufficient to enhance its clearance from the circulation.
PMID- 9643348
TI - The carboxyl terminus in apolipoprotein E2 and the seven amino acid repeat in
apolipoprotein E-Leiden: role in receptor-binding activity.
AB - Both apolipoprotein (apo) E2 and apoE-Leiden (tandem repeat of amino acids 121
127) are associated with type III hyperlipoproteinemia and bind defectively to
low density lipoprotein receptors. Removing the carboxyl terminus of both
variants (residues 192-299) increases receptor-binding activity, suggesting that
the carboxyl terminus modulates activity. To identify the region(s) that
modulated binding activity, we produced carboxyl-terminal truncations in apoE2
and apoE-Leiden (terminating at positions 191, 223, 244, and 272) and in apoE3
(terminating at positions 191, 223, and 244) and compared their receptor-binding
activities as dimyristoylphosphatidylcholine (DMPC) discs. The results suggest
that the entire carboxyl terminus up to residue 272, not a discrete smaller
segment, is responsible for the modulation in apoE2. Intact apoE-Leiden and the
223 and 244 variants displayed similar activities (approximately 25% of apoE3's),
but the 191 variant's activity was identical to that of intact apoE3. ApoE-Leiden
and its truncated variants formed larger DMPC discs than did intact or truncated
apoE3 or apoE2. These discs contained more apoE molecules than apoE3 discs,
suggesting that the apparently normal binding activity of the apoE-Leiden 191
variant results from an increased number of apoE molecules and that the binding
activity is actually defective. Direct comparison in a solid-phase assay revealed
that the binding activity of the apoE-Leiden fragment was defective (51.4+/
9.4%). Thus, the defective binding of apoE-Leiden results from a direct effect of
the seven amino acid repeat on receptor-binding activity rather than from an
indirect effect operating through the carboxyl terminus as previously believed.
PMID- 9643349
TI - Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic
apolipoprotein E*3-Leiden transgenic mice.
AB - Studying the effects of dietary fish oil on VLDL metabolism in humans is subject
to both large intra- and interindividual variability. In the present study we
therefore used hyperlipidemic apolipoprotein (APO) E*3-Leiden mice, which have
impaired chylomicron and very low density lipoprotein (VLDL) remnant metabolism,
to study the effects of dietary fish oil on serum lipids and VLDL kinetics under
highly standardized conditions. For this, female APOE*3-Leiden mice were fed a
fat- and cholesterol-containing diet supplemented with either 0, 3 or 6% w/w
(i.e. 0, 6, or 12% of total energy) of fish oil. Fish oil-fed mice showed a
significant dose-dependent decrease in serum cholesterol (up to -43%) and
triglyceride levels (up to -60%), mainly due to a reduction of VLDL (-80%). LDL
and HDL cholesterol levels were not affected by fish oil feeding. VLDL-apoB
kinetic studies showed that fish oil feeding resulted in a significant 2-fold
increase in VLDL-apoB fractional catabolic rate (FCR). Hepatic VLDL-apoB
production was, however, not affected by fish oil feeding. VLDL-triglyceride
turnover studies revealed that fish oil significantly decreased hepatic VLDL
triglyceride production rate (-60%). A significant increase in VLDL-triglyceride
FCR was observed (+70%), which was not related to increased lipolytic activity.
We conclude that APOE*3-Leiden mice are highly responsive to dietary fish oil.
The observed strong reduction in serum very low density lipoprotein (VLDL) is
primarily due to an effect of fish oil to decrease hepatic VLDL triglyceride
production rate and to increase VLDL-apoB fractional catabolic rate.
PMID- 9643350
TI - LPL promoter -93T/G transition influences fasting and postprandial plasma
triglycerides response in African-Americans and Hispanics.
AB - The lipoprotein lipase (LPL) promoter -93T/G transition has previously been
reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant
has been shown to have a Tg-raising effect. These two variants were studied in 66
healthy subjects of Hispanic and 42 subjects of African-American origin, who had
participated in a study of postprandial lipemia. While the allele frequency of
the -93G was significantly different in the Hispanics and African Americans
(0.09: 95% CI 0.04-0.13 and 0.28: 95% CI 0.19-0.38; P=0.0001, respectively), the
N9 allele frequency was not different (0.06: 95% CI 0.02-0.1 and 0.05: 95% CI
0.002-0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was
highly significant in Hispanics (delta=0.67. P=0.0001), compared to delta=0.09
(NS) in African-Americans. In the combined group, compared to individuals with
the common genotype (TT/DD; n=71) with fasting plasma Tg of 1.34 (+/-4.5% SEM)
mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n=25) had significantly
lower plasma Tg levels of 1.08 (+/-10% SEM) mmol/l (P < 0.02). After the fat
meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D
haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl
palmitate concentration at 5 hrs was significantly lower in G/D carriers than
TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in
carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was
not significant in this group. Thus carriers of the G/D haplotype have lower
fasting plasma Tg and reduced alimentary lipemia. This allele may be associated
with reduced risk of coronary artery disease.
PMID- 9643351
TI - Phospholipase A2 relieves phosphatidylcholine inhibition of micellar cholesterol
absorption and transport by human intestinal cell line Caco-2.
AB - Cholesterol absorption from bile acid micelles is suppressed by
phosphatidylcholine (PC) in the micelles. The effects of micellar phospholipid
composition on absorption, metabolism, and secretion of lipids were examined in
Caco-2 cells incubated with micelles composed of taurocholic acid, cholesterol,
oleic acid, monooleoylglycerol, and phospholipid. Significant amounts of all
micelle lipids were absorbed from micelles lacking phospholipid. Cholesterol
absorption was accompanied by cholesterol esterification and secretion. Micellar
oleic acid was also absorbed and reesterified primarily into triacylglycerol
which was also secreted. Lipid absorption and secretion from micelles containing
lysophosphatidylcholine (LPC) were similar to that obtained with phospholipid
free micelles. LPC was also extensively absorbed. In contrast, incubations with
PC-containing micelles resulted in large reductions in the absorption,
esterification, and secretion of cholesterol without significant decreases in
oleic acid absorption, conversion to acylated lipids, or triacylglycerol
secretion. A relatively small reduction in monoacylglycerol absorption from PC
containing micelles was detected. Retinol absorption was not affected by micellar
PC. Substitution of LPC for half or more of the PC reversed the PC-dependent
decrease in cholesterol absorption. Pancreatic phospholipase A2 (pPLA2) enhanced
cholesterol absorption from PC-containing micelles. The pPLA2-dependent increase
in cholesterol absorption was inhibited by the pPLA2 inhibitor FPL 67047XX. The
results indicate micellized cholesterol absorption by enterocytes is uniquely
dependent on the elimination of micellar phosphatidylcholine and thus directly
dependent on the lipolytic action of pancreatic phospholipase A2 (pPLA2).
Consequently, pPLA2 inhibitors may be a new and novel class of cholesterol
absorption inhibitors for therapeutic use.
PMID- 9643352
TI - Involvement of cytochrome P450 2E1 in the (omega-1)-hydroxylation of oleic acid
in human and rat liver microsomes.
AB - In vitro techniques have been used to investigate the nature of microsomal
cytochrome P450 involved in the metabolism of oleic acid, a physiological
monounsaturated fatty acid. Like lauric acid, which is currently used as a model
substrate of fatty acid metabolism, the alkyl chain of oleic acid is hydroxylated
on its omega and (omega-1) carbons. The identity of these hydroxylated
metabolites was ascertained by GC/MS and LC/MS. The omega/omega-1 ratio of oleic
acid metabolites (1.22+/-0.01) was found to be similar to that obtained with
lauric acid in rat liver microsomes (1.10+/-0.02), while in human liver
microsomes this ratio was 0.75+/-0.5 for lauric acid and 5.2+/-2.6 for oleic
acid. After treatment of rats with ethanol or clofibrate, inducers of CYP2E1 and
CYP4A, respectively, the hydroxylations of oleic acid were shown to be less
inducible than those of lauric acid. Five in vitro approaches were used to
identify the P450 isoform(s) responsible for the microsomal (omega-1)
hydroxylation of oleic acid: effect of various inducers in rats, correlation
studies between specific P450 catalytic activities in a panel of 25 human liver
microsomes, chemical inhibitions, immuno-inhibitions and metabolism by cDNA
expressed human P450 enzymes. From the above results, it can be ascertained that
P450 2E1 is the main enzyme involved in the (omega-1)-hydroxylation of oleic
acid. Furthermore, the omega-hydroxylation of oleic acid was shown to be mainly
catalyzed by P450 4A enzymes in human liver microsomes. The turnover number of
(omega-1)-hydroxylation of lauric and oleic acids decreased from 7.8 to 1.5 min(
1), respectively, suggesting that the dodecane alkyl chain allows optimal binding
to the active site of CYP2E1.
PMID- 9643353
TI - Regulation of microsomal triglyceride transfer protein mRNA expression by
endotoxin and cytokines.
AB - We studied the effect of endotoxin (LPS), and cytokines (TNF, IL-1, and IL-6) on
hepatic microsomal triglyceride transfer protein (MTP) mRNA levels in vivo in
Syrian hamsters and in vitro in HepG2 cells. LPS, interleukin-1 (IL-1), and to a
lesser extent tumor necrosis factor (TNF) significantly decreased MTP mRNA levels
in hamster liver. These effects required several hours. Furthermore, IL-1 and IL
6 significantly decreased MTP mRNA levels in HepG2 cells. This decrease appeared
soon after IL-1 administration (8 h) and at very low doses (0.1 ng/ml). MTP
activity and protein levels of the large subunit of MTP also decreased modestly
in HepG2 cells with prolonged cytokine treatment. IL-1 reduced the expression of
an MTP promoter luciferase construct to a similar degree as seen with MTP mRNA,
indicating that transcriptional regulation plays a major role in the decrease of
MTP gene expression. Deletional analysis of the MTP promoter identified the
region -121 to -88 bp upstream to the coding sequence as the site of the negative
regulation by IL-1. This region contains an insulin response element (IRE),
activating protein 1 (AP-1), hepatic nuclear factor 1 (HNF-1) and hepatic nuclear
factor 4 (HNF-4) consensus sequences; mutations of the IRE and HNF-4 sites did
not affect the response to IL-1. In contrast, mutating AP-1 or HNF-1 sites led to
a marked decrease in basal expression and the loss of the IL-1 effect, suggesting
that an intact AP-1 and/or HNF-1 regulatory element are crucial for the IL-1
regulation of MTP gene expression. However, prolonged incubation with IL-1 did
not alter HepG2 apolipoprotein B secretion suggesting that MTP mRNA down
regulation does not contribute significantly to the cytokine-induced effects on
lipid metabolism.
PMID- 9643354
TI - Differential rate of cholesterol efflux from the apical and basolateral membranes
of MDCK cells.
AB - Epithelial cells contain two distinct membrane surfaces, the apical and
basolateral plasma membranes, which have different lipid and protein
compositions. In order to assess the effect of the compositional differences of
the apical and basolateral membranes on their ability to undergo cholesterol
efflux, MDCK cells were radiolabeled with [3H]cholesterol and grown as a
polarized monolayer on filter inserts, that separate the upper apical compartment
from the lower basolateral compartment. The rate of cholesterol efflux from the
basolateral membrane into media containing HDL in the basolateral compartment was
6.3%/h +/-0.7, whereas HDL-mediated efflux from the apical membrane was
approximately 3-fold slower (1.9%/h +/-0.3). In contrast, Fu5AH cells, which do
not form distinct polarized membrane domains, had a similar rate of HDL-mediated
cholesterol efflux into the apical and basolateral compartments. Similar to HDL,
other cholesterol acceptors, namely LDL, bovine serum albumin, and a lipid
emulsion, also showed a decreased rate of cholesterol efflux from the apical
membrane surface versus the basolateral membrane. Compared to the basolateral
membrane, the apical membrane was also found to be more resistant to cholesterol
oxidase treatment, to bind less HDL, and to take up less cholesterol from the
medium. In conclusion, cholesterol efflux occurred less readily from the apical
membrane than from the basolateral membrane for all types of acceptors tested.
These results suggest that differences in the composition of the apical and
basolateral membrane lead to a relative decrease in cholesterol desorption from
the apical membrane and hence a reduced rate of cholesterol efflux.
PMID- 9643355
TI - Liposomes enriched in oleic acid are less susceptible to oxidation and have less
proinflammatory activity when exposed to oxidizing conditions.
AB - As there is frequently a reciprocal relationship between oleic acid and linoleic
acid content in LDL after dietary supplementation, it is difficult to determine
the independent effects of oleic and linoleic acid on LDL oxidation. It is also
unknown whether monounsaturated fatty acid enrichment might reduce the generation
of proinflammatory products that occur when the polyunsaturated fatty acid-rich
phospholipids within lipoproteins undergo mild oxidation. To address these
issues, we exposed liposomes containing variable amounts of oleic, linoleic, and
arachidonic acid to oxidizing conditions. Liposomes enriched in oleic acid but
with constant amounts of linoleic acid were less susceptible to oxidation and had
significantly greater lag times and time to half maximum conjugated diene
formation. When mildly oxidized, liposomes containing either linoleic acid or
arachadonic acid increased monocyte chemotaxis and monocyte adhesion to
endothelial cells nearly 5-fold, demonstrating that oxidation products of both
these polyunsaturated fatty acids are bioactive. The addition of a platelet
activating factor receptor antagonist to endothelial cells inhibited stimulation
of monocyte adhesion by oxidized liposomes, suggesting that some bioactive
oxidation products of polyunsaturated fatty acids may resemble platelet
activating factor in structure. In contrast, when liposomes were enriched in
oleic acid, monocyte chemotaxis and monocyte adhesion were nearly completely
inhibited. These results suggest that enriching lipoproteins with oleic acid may
reduce oxidation both by a direct "antioxidant"-like effect and by reducing the
amount of linoleic acid available for oxidation as well as reduce the generation
of bioactive particles that occur during mild oxidation.
PMID- 9643356
TI - Adenovirus mediated overexpression of human phospholipid transfer protein alters
plasma HDL levels in mice.
AB - To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a
liver directed adenoviral gene transfer system was used to overexpress human PLTP
in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice
transgenic for the human apoA-I gene (HuApoA-ITg), were utilized. Five days after
injection of the recombinant PLTP adenovirus, wild type mice showed a 4-fold
increase in serum PLTP activity in (12.2+/-1.3 micromol/ml per h to 48.1+/-8.6
micromol/ml per h (+394%), P < 0.001). The PLTP overexpression induced
significant reduction of serum cholesterol (2.46+/-0.08 to 0.69+/-0.42 mmol/l (
72%), P < 0.001), phospholipids (3.10+/-0.06 to 0.90+/-0.24 mmol/l (-71%), P <
0.01), and triglycerides (0.2+/-0.07 to 0.08+/-0.03 mmol/l (-69%), (P < 0.001).
ApoA-I was hardly detectable in the serum. These lipid changes were due to a
dramatic reduction of high density lipoprotein (HDL). The HuApoA-ITg mice
displayed higher basal HDL level and PLTP activity. Adenovirus mediated PLTP
overexpression in these mice resulted in a similar decrease of the lipid levels
as that seen in the C57/B1 mice. However, the lipoprotein profile revealed a
redistribution of HDL, with the appearance of larger buoyant HDL species. The
results demonstrate that plasma phospholipid transfer protein in vivo causes high
density lipoprotein (HDL) conversion and thereby plays a central role in HDL
metabolism.
PMID- 9643357
TI - 13-hydroxy octadecadienoic acid (13-HODE) inhibits triacylglycerol-rich
lipoprotein secretion by CaCo-2 cells.
AB - Oxidized lipids present in atherogenic lipoproteins are derived, in part, from
the diet. To address the effects of an oxidized lipid on intestinal lipoprotein
assembly and secretion, CaCo-2 cells were incubated with 13-HODE or its native
fatty acid, linoleic acid, and triacylglycerol-rich lipoprotein synthesis and
secretion were investigated. 13-HODE was readily taken up by cells and esterified
to lipids. Although both fatty acids were largely esterified to neutral lipids,
in comparison to neutral lipids containing linoleic acid, a greater proportion of
cellular neutral lipids containing 13-HODE and/or its metabolites was secreted.
Compared to linoleic acid, however, 13-HODE caused less triacylglycerol, derived
from de novo synthesis, and less triacylglycerol mass to be secreted. Cells
incubated with both linoleic acid and 13-HODE together secreted less
triacylglycerol mass than did cells incubated with linoleic acid alone. Less
newly synthesized apoB and apoB mass were secreted by cells incubated with 13
HODE without altering the abundance of apoB mRNA. The fraction of newly
synthesized apoB translocated into the secretory pathway of cells exposed to 13
HODE was significantly less than that observed in cells incubated with linolenic
acid, suggesting that 13-HODE interfered with the assembly and secretion of
triacylglycerol-rich lipoprotein particles.
PMID- 9643358
TI - Small dense low density lipoprotein has increased affinity for LDL receptor
independent cell surface binding sites: a potential mechanism for increased
atherogenicity.
AB - Small dense low density lipoprotein (LDL) particles have altered apolipoprotein
(apo) B conformation and lowered affinity for the LDL receptor (J. Biol. Chem.
1994. 269: 511-519). Herein, we examine the interaction of small dense LDL with
cell LDL receptor-independent binding sites. Compared to normal LDL, at low LDL
cell media concentrations (<10 microg/ml), small dense LDL had decreased specific
binding to the LDL receptor on normal fibroblasts at 4 degrees C, but a 2-fold
increased binding to LDL receptor-independent cell sites. At higher LDL
concentration (100 microg/ ml), LDL receptor-independent binding of small dense
LDL was 4.5-fold that of normal LDL in normal fibroblasts, but greater (2- to 14-
fold) in LDL receptor-negative fibroblasts. In LDL receptor-negative fibroblasts
at 37 degrees C, small dense LDL had higher (3-fold) cell association than normal
size LDL but no effective LDL degradation. At high LDL concentrations (> or =100
microg/ml), LDL binding to normal or LDL receptor-negative fibroblasts was not
affected by several anti-apoB monoclonal antibodies or by cell pretreatment with
proteases, chondroitinase, or neuraminidase. In contrast, pretreating normal and
receptor-negative fibroblasts with heparinase and heparitinase decreased LDL cell
binding by 35% and 50%, respectively. Similarly, preincubation of receptor
negative fibroblasts with sodium chlorate, an inhibitor of proteoglycan
sulfation, decreased LDL binding by about 45%. We hypothesize that small dense
LDL might be more atherogenic than normal size LDL due to decreased hepatic
clearance by the LDL receptor, and enhanced anchoring to LDL receptor-independent
binding sites in extrahepatic tissues (e.g., the arterial wall), a process
mediated, in part, by cell surface proteoglycans.
PMID- 9643359
TI - Effect of diet on the rate of depletion of n-3 fatty acids in the retina of the
guinea pig.
AB - This study has assessed the influence of maternal n-3 long chain polyunsaturated
fatty acid supply and dietary manipulation after weaning on the retinal
polyunsaturated fatty acid profile. Infant guinea pigs born of dams fed one of
two commercial chow diets (differing in the amount of eicosapentaenoic,
docosapentaenoic, and docosahexaenoic acids) were raised in two separate
experiments, and subsequently partitioned into two diet groups, one supplied with
a high level of alpha-linolenic acid (canola oil supplemented), the other with a
very low level of alpha-linolenic acid (safflower oil supplemented). Guinea pigs
born of dams supplied with the longer chain n-3 fatty acids in the commercial
pellets (experiment 2) showed higher levels of retinal docosahexaenoic acid at
weaning compared with those born to dams fed chow containing only alpha-linolenic
acid (experiment 1). The rate of depletion of retinal docosahexaenoic acid after
weaning onto the safflower oil diet was described by a two-stage exponential
decay, possibly reflecting systemic and local conservation mechanisms, in
conditions of dietary n-3 fatty acid deprivation. The rate of docosahexaenoic
acid depletion in the group with the lower retinal docosahexaenoic acid at
weaning was more than double the rate of depletion in the group with the higher
weaning docosahexaenoic acid value. The endpoint retinal docosahexaenoic acid
level at 16 weeks post-weaning after dietary n-3 fatty acid depletion on the
safflower oil diet in the group, which started with the lower retinal
docosahexaenoic acid level, was approximately half that compared with the group
from the dams fed long chain n-3 fatty acids (experiment 1, 5% (interpolated),
experiment 2, 9%). These results suggest that an adequately supplied mother is
capable of providing an infant with enough n-3 fatty acids to withstand a longer
period of dietary deprivation imposed after weaning.
PMID- 9643360
TI - Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men.
AB - Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver
and principally from two sources: FA synthesized de novo in the liver and
preformed FA. We have measured the contribution from the two sources to very low
density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate,
stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL
TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state,
and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate
enriched diet (approximately 2.5 times energy expenditure). The secretion of de
novo palmitate was increased 15- and 43-fold after 1 and 4 days of
hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0
micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the
secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/
0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal),
28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the
de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease
the secretion while 4 days increased the secretion of all preformed FA in VLDL
TG. The rate of secretion of preformed palmitate and oleate were almost identical
(palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1
micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and
356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted
for 80-90% of the secretion from the preformed source. Palmitate is the
predominant product of acute and prolonged carbohydrate mediated lipogenesis in
the human liver. The pathway of further elongation and subsequent desaturation of
de novo synthesized palmitate to generate stearate and oleate is inducible but,
quantitatively, of minor significance in hepatic lipogenesis.
PMID- 9643361
TI - Translocational pausing of apolipoprotein B can be regulated by membrane lipid
composition.
AB - One potential mechanism by which apolipoprotein (apo) B secretion is regulated is
via transient pausing during translocation across the endoplasmic reticulum
membrane. We have previously shown that translocation and secretion of full
length and truncated variants of apoB 100 are impaired in hepatocytes in which
microsomal membranes are enriched in the phospholipid
phosphatidylmonomethylethanolamine (PMME). We have now investigated whether or
not the decreased translocation of apoB is the result of altered membrane lipid
composition having an impact on translocational pausing. Our experiments showed
that less in vitro translated apoB-15 (the N-terminal 15% of human apoB-100) was
translocated into the lumen of PMME-enriched microsomes than of control
microsomes. Proteinase K treatment of the translocation products yielded discrete
N-terminal fragments of apoB indicating that both types of microsomal membranes
contained translocationally paused nascent chains. Similarly, apoB generated from
a truncated mRNA lacking a stop codon was also found to be translocationally
paused. However, restarting of translocation after translocational pausing was
impaired in PMME-enriched, but not in control, microsomes. These data suggest
that secretion of apoB-containing lipoproteins can be regulated by membrane lipid
composition at the level of translocational pausing.
PMID- 9643362
TI - Metabolic fate of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero
3-phosphocholine) and lyso-PAF (1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) in
FRTL5 cells.
AB - The metabolism of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero
3-phosphocholine) and lyso-PAF (1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) was
investigated in FRTL5 cells, a normal rat thyroid cell line. FRTL5 cells
incorporated [3H]PAF and deacetylated this compound to the corresponding [3H]lyso
PAF which was not accumulated or secreted but converted mainly to alkyl-acyl
phosphocholine indicating that this acylation process was particularly active in
these cells. Among metabolic products of both [3H]PAF and [3H]lyso-PAF were
alkylglycerol as well as its mono- and diacyl derivatives. [3H]alkylglycerol
could be the intermediate compound for the production of [3H]alkyl- and
[3H]alkenyl-phosphoethanolamine (plasmalogen) which were also metabolic products.
FRTL5 cells were able to convert lyso-PAF to PAF especially when they were
stimulated by ionophore A23187 in the presence of [3H]Iyso-PAF and
phenylmethylsulfonyl fluoride. The amount of PAF increased for the first 30 min
and declined thereafter. PAF resting levels were found low in the same cells.
Furthermore, PAF-acetylhydrolase activity was determined in cell homogenates. The
presence of metabolic products such as alkyl-phosphatidylcholine, alkyl- and
alkenyl-phosphatidylethanolamine and alkyl-glycerol, as well as, its mono- and
diacyl derivatives, indicates that FRTL5 cells and probably other thyroid cells,
are very active in metabolizing PAF and lyso-PAF and suggests the co-operation of
the corresponding metabolic pathways in these cells.
PMID- 9643363
TI - Capillary electrophoresis to monitor the oxidative modification of low density
lipoproteins.
AB - A procedure has been developed that uses high performance capillary
electrophoresis to monitor the changes in the electrophoretic mobility of low
density lipoproteins (LDL) resulting from Cu2+-catalyzed lipid peroxidation.
Using uncoated fused silica capillaries, methylglucamine-Tricine, pH 9.0, as
electrophoresis buffer and a field strength of 350 V/cm, separation of native LDL
and oxidized LDL could be achieved in 8-10 min. The electrophoretic mobility of
native LDL under these conditions was 1.32 x 10(-4) cm2 x V(-1) x s(-1), and the
migration time could be measured with a coefficient of variation of 0.44%. The
increase in the electronegativity of LDLs during incubation with 10 microM Cu2+
for 0.25-2.0 h resulted in a progressive increase in migration time. Monitoring
the absorbance of the migrating LDL particles at a wavelength of 234 nm showed a
progressive increase in peak area, which paralleled that in diene conjugation
measured spectrophotometrically. Electronegative LDL particles formed by
modification with malondialdehyde could also be separated from native LDL
particles under these conditions. This new procedure should be useful in studies
of factors influencing low density lipoprotein oxidation in vitro and in vivo.
PMID- 9643364
TI - Identification of a heparin-binding domain in the distal carboxyl-terminal region
of lipoprotein lipase by site-directed mutagenesis.
AB - The interaction of lipoprotein lipase (LPL) with heparan sulfate proteoglycans
plays an important role in the metabolism and catalytic function of the enzyme.
We have used site-directed mutagenesis to replace the basic residues contained in
a discontinuous charge cluster (residues Lys 321, Arg 405, Arg 407, Lys 409, Lys
415, and Lys 416) of avian LPL with asparagine. The mutant proteins were
expressed in Chinese hamster ovary cells and their affinity for heparin was
evaluated by heparin-Sepharose chromatography. Mutation of residues Lys 321, Arg
405, Arg 407, Lys 409, and Lys 416 resulted in a decrease in affinity for
heparin. The triple mutant LPL(R405N, R407N, K409N) possessed almost no high
affinity binding. The LPL mutants showed enzymatic activities ranging between 50
100% of that seen for wild-type LPL demonstrating that the overall structure of
the enzyme was not significantly altered by the mutations. Mutation of previously
identified heparin-binding regions of LPL results in a relatively small decrease
in heparin-binding affinity, as compared with mutations in this carboxyl-terminal
region, indicating that Lys 321, Arg 405, Arg 407, Lys 409, and Lys 416
constitute the major heparin-binding domain in LPL.
PMID- 9643365
TI - Fluoride distribution in sound and carious root tissues of human teeth.
AB - Proton probe analysis has been used to provide for the first time quantitative F
concentration data in carious root tissues from subjects consuming water
containing 1 ppm F. In small lesions at the neck of the tooth with minimal tissue
loss the F concentration was significantly higher at the outer lesion edge than
at the outer edge of adjacent sound root tissue. In one sample with high F values
the lesion edge had 19,000 ppm F and the adjacent sound root surface 5,400 ppm F
microg F/g apatite). In large lesions with extensive cavitation F was again
concentrated in the outer edge of the lesion and was significantly higher (1,800
4,100 ppm) than in adjacent sound inner dentine (190-290 ppm). Fluoride
concentrations varied markedly along the outer edge of both normal and carious
root tissues. Fluoride increase at the lesion edge is not an effect of tissue
shrinkage but probably a result of remineralisation events during caries. This
additional F may be expected to increase tissue resistance to further acid
attacks.
PMID- 9643366
TI - Detection, diagnosing, monitoring and logical treatment of occlusal caries in
relation to lesion activity and severity: an in vivo examination with
histological validation.
AB - The aims of the present study were to investigate the ability of 3 experienced
clinicians to detect occlusal carious lesions, assess their depth, diagnose their
activity and define a logical management for each lesion. The material consisted
of 35 third molars scheduled for extraction or surgical removal making it
possible to validate the accuracy of the clinical recordings histologically.
Examinations were carried out at baseline and after 4 months in order to monitor
lesion progression. At the first visit a radiograph was taken; the number of
filled surfaces was counted and the oral hygiene assessed generally and by
disclosing occlusal plaque of the tooth under examination. After cleaning the
occlusal surface caries was recorded in a selected investigation site using a
visual ranked caries scoring system, as well as an electrical conductance
recording (ECM). Apart from counting fillings and taking new radiographs the same
procedure was performed at the second visit, which then was followed by
extraction of the tooth. After sectioning the tooth lesion depth was recorded,
and lesion activity, based on acid production, was assessed using methyl red dye.
Lesion activity was also judged by means of polarized light microscopic
examinations of the sections. Results showed strong relationships between the
visual, ECM and radiographic assessments and both lesion depth and lesion
activity. In contrast, all other parameters were poorly related to lesion
activity. Changes in visual assessments and in conductance readings from first to
second examination were poorly associated with lesion activity. In conclusion,
clinicians are able to detect lesions, predict activity and severity and define a
logical management of occlusal caries on the basis of a single examination.
PMID- 9643367
TI - An in vitro system for the analysis of changes in depth distribution of
diffusates in bacterial films.
AB - No suitable technique exists which allows simultaneous analysis of time- and
depth-dependent concentrations of all components of interest in single samples of
intercellular fluid from dental plaque biofilms. We have developed an in vitro
model which allows detailed study of these interactions by analysis of
intercellular fluid and pH measurement at the film base. Compact, defined-depth
films of Streptococcus mutans were formed in a micrometer-controlled, variable
depth well and bathed in synthetic saliva. Films exposed to synthetic saliva
containing glucose for 2 min followed by clearance with glucose-free synthetic
saliva gave typical 'Stephan-type' pH profiles. Intercellular fluid isolated from
successive 200-microm-thick sections of 600-microm-deep films was analysed by ion
chromatography. A concentration gradient of lactate, falling with depth, was
measured. The experimental system described here, the first of its type to be
described, can easily be used to analyse pH changes and the depth-dependent
distribution of diffusates in a model bacterial film. Although this bacterial
film is far removed from a natural biofilm, the apparatus has potential for the
study of grown biofilms and is an important advance towards position-dependence
analysis of diffusates in biofilms.
PMID- 9643368
TI - Dental caries susceptibility in mice is closely linked to the H-2 region on
chromosome 17.
AB - The generation of dental caries in humans is thought to be regulated by many
intrinsic and social factors. In this study, we examined the effect of MHC on
susceptibility to dental caries in mice. The mean carious score of BALB.K/Ola, a
H-2 congenic strain in which the H-2 region derived from C3H/HeJ (H-2(k/k)) is
introduced into BALB/cJ (H-2(d/d)), was markedly reduced as compared with that of
its recipient strain (BALB/cJ). Mating experiments confirmed a strong genetic
linkage between H-2 haplotype and caries susceptibility. These results
demonstrate that one of the genetic factors of the susceptibility in the mouse is
mapped within the H-2 region. This finding of a host genetic factor influencing
the generation of dental caries will help in developing clinical preventive
strategies.
PMID- 9643369
TI - The effect of fluoridation on the occurrence of hidden caries in clinically sound
occlusal surfaces.
PMID- 9643370
TI - Programmed cellular response in radiation oncology.
PMID- 9643371
TI - Effect of curdlan sulfate on the production of beta-chemokines and cytokines.
PMID- 9643372
TI - Immunization with both T cell-dependent and T cell-independent vaccines augments
HIV viral load secondarily to stimulation of tumor necrosis factor alpha.
AB - Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4
cell counts, and might influence disease progression. Because these deleterious
effects are postulated to be secondary to a direct activation of T lymphocytes
induced by the immunogen, we compared immunologic and virologic effects of a T
cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children
were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO)
(T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and
type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and
28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and
6 months after vaccination were not significantly different. HIV viral load
increased in both groups of children despite the fact that type 1 cytokine
production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in
PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of
T cell activation (as measured by cytokine production) was observed in PNEUMO
vaccinated children. Because polysaccharides of the bacterial cell wall stimulate
TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate
HIV replication directly on activation of NF-kappa b after binding the long
terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and
observed a significant increase in both groups of vaccines. These data suggest
that an increase in HIV viral load can be observed in vaccinated HIV-infected
children even independent of direct antigen-induced activation of T lymphocytes,
and that augmented production of TNF-alpha might play a role in this phenomenon.
PMID- 9643373
TI - Neutralizing antibodies directed against the V3 loop select for different escape
variants in a virus with mutated reverse transcriptase (M184V) than in wild-type
human immunodeficiency virus type 1.
AB - The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse
transcriptase (RT) encodes high-level resistance to the (-)-enantiomer of 2',3'
dideoxy-3'-thiacytidine (3TC) and low-level resistance to each of 2',3'
dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). This mutation also results
in decreased HIV replication fitness in primary cells, diminished RT
processivity, and increased RT fidelity. To assess the effect of this
substitution on genetic variation in the HIV env region, we cultured both M184V
containing and wild-type BH10 in MT-4 cells in the presence of the neutralizing
monoclonal antibody 447-52D, targeted to the GPGR epitope within the V3 loop of
gp120. Outgrowth of viruses resistant to neutralization was followed by sequence
analysis of the V3 loop by standard methodology. Wild-type HIV first showed
escape after 15-22 days in culture. Sequence analysis revealed an arginine-to
lysine change within the GPGR epitope in the V3 loop (R20K, AGA --> AAA) in six
of six clones sequenced after day 36. In contrast, M184V-containing HIV first
showed escape between days 25 and 32 and sequence analysis revealed an aspartate
to-tyrosine change at amino acid 5 in V3 (N5Y; AAC --> TAC) in two of six clones
at day 36 and in five of five clones at day 55. Similar results were obtained in
two independent antibody selection protocols. The escape mutation in the wild
type is consistent with the G --> A hypermutation observed in wild-type HIV-1,
recently shown to cause an initial M184I change (before M184V) in 3TC-treated
patients. In contrast, the N5Y substitution seen with M184V-containing HIV-1 is
an A --> T transversion in V3.
PMID- 9643374
TI - Cross-clade p17 peptide recognition by antisera to HGP-30, a 30-amino acid
synthetic peptide antigen from HIV type 1 p17.
AB - HGP-30, a 30-amino acid synthetic peptide analog of HIV-1SF2 p17 (aa 86-115), was
used to immunize both mice and humans. Since the amino acid sequence of HGP-30 is
relatively conserved among different HIV-1 strains and clades, experiments were
carried out to determine if antisera obtained by immunizing animals and humans
can recognize HGP-30-related peptide consensus sequences belonging to different
clades. Results show that antisera from mice immunized with HGP-30 can recognize
clade B and C and to a lesser degree clade A and E consensus sequences of HIV-1,
in addition to recognizing HGP-30 sequence. The cross-clade recognition was
higher in mouse sera obtained on day 42 than on day 14 or 28. MPL/SE and
Novasomes were better adjuvants than alum in inducing antibodies that showed
cross-clade recognition and IgG2a and IgG2b antibody isotypes. Similar cross
clade recognition was observed in several sera from humans immunized with an HGP
30/KLH/alum formulation. The human sera from HGP-30-immunized subjects evaluated
for cross-clade recognition of HGP-30 peptides were from subjects whose cells
showed significant protection from HIV infection on virus challenge in the hu-PBL
SCID mouse model. These studies suggest that HGP-30 may be useful as a candidate
vaccine antigen for populations in countries with prevalence of different HIV
clades.
PMID- 9643375
TI - Hypervariable epitope constructs representing variability in envelope
glycoprotein of SIV induce a broad humoral immune response in rabbits and rhesus
macaques.
AB - Using synthetic peptides, we developed an approach to account for protein epitope
variability. We have prepared, in a single synthesis, a cocktail of peptides we
have designated a hypervariable epitope construct (HEC), which collectively
represents much of the in vivo variability seen in an epitope. Eight HECs
representing the in vivo variability seen throughout the envelope glycoprotein of
the simian immunodeficiency virus (SIV) were designed and synthesized. The
constructs were collectively conjugated to KLH (HEC-KLH) or recombinant gp130
(HEC-rgp130) and used to immunize rabbits and rhesus macaques, respectively.
Using sera collected from rabbits immunized with HEC-KLH, we demonstrated that
individual components of the immunogen were recognized as antigen in ELISAs, and
that the induced antibodies cross-reacted with several strains of SIV as well as
with a strain of HIV-2. Following immunization of macaques with HEC-rgp130
antiviral antibodies were induced. These antibodies were still present 9.5 months
after the last boost and were also capable of recognizing several different
strains of SIV, including SIVmac239, SIVmac251, and SIVsmH3, as well as a strain
of HIV-2 (HIV-2ROD). In addition, the antibodies were also capable of
neutralizing SIV viral infectivity in vitro. Peripheral blood lymphocytes (PBLs)
from immunized macaques proliferated in response to whole proteins and virus.
Finally, sera from monkeys immunized with SIV, rgp130, and HIV-2 as well as sera
from HIV-2-positive humans recognized HECs in ELISAs, demonstrating the relevance
of these epitopes in vivo. This approach can be used as an effective method for
generating a strong, broadly cross-reactive humoral response against HIV and can
serve as an important component of combination vaccines against HIV and AIDS.
PMID- 9643376
TI - Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of
perinatal simian immunodeficiency virus infection in rhesus macaques.
AB - Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful
animal model to explore novel strategies to reduce perinatal human
immunodeficiency virus (HIV) infection. The availability of two easily
distinguishable virus isolates, SIVmac251 and the simian/human immunodeficiency
virus chimera SHIV-SF33, allows tracing the source of infection following
inoculation with both viruses by different routes. In the present study, we
evaluated the efficacy of pre- and postinoculation treatment regimens with 9-[2
(phosphonomethoxy)propyl]adenine (PMPA) to protect newborn macaques against
simultaneous oral SIVmac251 and intravenous SHIV-SF33 inoculation. Untreated
newborns became persistently infected following virus inoculation. When three
pregnant macaques were given a single subcutaneous dose of PMPA 2 hr before
cesarean section, their newborns became SIV-infected following SIV and SHIV
inoculation shortly after birth. In contrast, when four newborn macaques were
inoculated simultaneously with SIV and SHIV, and started immediately on PMPA
treatment for 2 weeks, only one animal became persistently SIV-infected; the
remaining three PMPA-treated newborns, however, had some evidence of an initial
transient virus infection but were seronegative and healthy at 8 months of age.
Our data demonstrate that PMPA treatment can reduce perinatal SIV infection and
suggest that similar strategies may also be effective against HIV.
PMID- 9643377
TI - Administration of interleukin 13 to simian immunodeficiency virus-infected
macaques: induction of intestinal epithelial atrophy.
AB - Increase Th2 cytokine production may contribute to some clinical manifestations
of HIV infection, and studies have suggested that IL-13 rather than IL-4 is
involved in these conditions. We directly tested this hypothesis by
administrating IL-13 to SIV-infected macaques. SIV-infected rhesus macaques
received a daily subcutaneous injection for 21 days of either IL-13 (10
microg/kg/day) or a placebo. The four macaques treated with IL-13 experienced
body weight loss (9.95 +/- 0.71%) related to intestinal tract damage: they all
suffered from a complete atrophy of duodenal villi. This was presumably due to
premature epithelial cell death: proliferating Ki67+ cells in glandular crypts
were as numerous as in control animals, but many epithelial cells developed
apoptosis. The duodenal mucosa was infiltrated with cells expressing CD56 and
PEN5, two markers of NK cells, and there was a deregulation of local cytokine and
chemokine production characterized by a decrease in IL-10 gene expression (25% of
controls) and an increase in gene expression for IFN-gamma (4-fold control), MIP
1alpha (8-fold control), and MIP-1beta (13-fold control). Thus, IL-13 can induce
digestive epithelial cell injury in vivo in primates infected with a retrovirus.
Therefore, its role should be considered in digestive manifestations of HIV
infection as well as in other disorders associated with intestinal epithelial
atrophy.
PMID- 9643378
TI - Phylogenetic analysis of SIV and STLV type I in mandrills (Mandrillus sphinx):
indications that intracolony transmissions are predominantly the result of male
to-male aggressive contacts.
AB - Natural SIVmnd and STLVmnd infections of mandrills in a colony at the Centre
International de Recherches Medicales de Franceville (CIRMF) in Gabon were
investigated by genetic analysis to determine the extent of intracolony
transmission. SIVmnd pol sequence analysis indicates that the six strains present
in the colony belong to the SIVmnd lentivirus subgroup previously defined
according to the only available prototype sequence (SIVmndGB1), which originated
from the same colony. The intraanimal nucleotide diversity (1.1-3.1%) was similar
in range to that reported in individuals infected by other HIV/SIVs. The
interanimal diversity (0.5-4.3%) was not significantly different from that
observed in each individual mandrill, indicating an epidemiological link among
the SIVmnd isolates of distinct animals within the colony. Phylogenetic analysis
of these isolates, together with seroepidemiological and behavior surveillance
within the colony, indicates a predominant male-to-male transmission of SIVmnd
that probably occurred during bouts of interanimal aggression. Moreover, our
results suggest one case of vertical transmission of SIVmnd from a naturally
infected founder female to one of her six offspring. The first genetic analysis
of STLV isolates from mandrills is also reported here. Partial tax/rex sequences
were used to evaluate the diversity between seven STLVmnd isolates and their
phylogenetic relationships with other known strains of human and nonhuman primate
T cell leukemia virus, types I and II (PTLV-I/II). They all belong to the PTLV-I
subtype, but two genetically distinct STLVmnd groups were evidenced within the
mandrill colony. The phylogenetic analyses of the STLVmnd isolates, together with
seroepidemiological and behavior surveillance of the mandrills, indicate that
intracolony transmissions of STLVmnd are also predominantly the result of male-to
male aggressive contacts.
PMID- 9643379
TI - Lessons from the cat: feline immunodeficiency virus as a tool to develop
intervention strategies against human immunodeficiency virus type 1.
PMID- 9643380
TI - Variation in HIV type 1 V3 region env sequences from Mozambique.
PMID- 9643381
TI - HIV type 1 env subtype A variants in Taiwan.
PMID- 9643382
TI - Genomic sequence of HIV type 1 from four members of the Sydney Blood Bank Cohort
of long-term nonprogressors.
PMID- 9643384
TI - Introduction: Legionnaires' disease.
PMID- 9643383
TI - Genetic and phylogenetic analysis of HIV type 1 strains from southern Ghana.
PMID- 9643385
TI - Legionnaires' disease: clinical, epidemiological, and public health perspectives.
AB - Legionnaires' disease is a modern environmental infectious disease. It stems from
the capacity of the causative agent, Legionella, to multiply within amoebae in
warm water and the use, during the 20th century, of devices that maintain water
at warm temperatures and produce aerosols. When contaminated with Legionella,
aerosols consisting of respirable droplets place the bacteria in juxtaposition
with alveolar macrophages, which, as with amoebae, they may parasitize, resulting
in illness in susceptible persons. The disease is much more common than
previously appreciated with at least 13,000 cases estimated to occur per year in
the United States, based on prospective studies. Two highly specific tests,
urinary antigen detection and sputum culture, are available for diagnosis during
illness. With 60% to 80% sensitivity, urinary antigen tests rapidly detect
antigens of Legionella pneumophila serogroup 1, which are responsible for 70% of
the cases of legionnaires' disease; results can be available within a few hours.
Culture of sputum is 50% to 60% sensitive, but several days are required for
growth, and many patients do not produce sputum. Serologic testing, although
useful for epidemiologic studies when convalescent-phase antibody titers can be
compared with acute-phase titers, is not helpful for clinical decision making
because of the low positive predictive value of commercially available acute
phase serologic tests. Erythromycins, intravenous azithromycin, and levofloxacin
are currently approved by the US Food and Drug Administration for treatment of
legionnaires' disease. However, clarithromycin and several other fluoroquinolones
are active against Legionella and may also provide effective therapy. Recent
recommendations from the Centers for Disease Control and Prevention's Hospital
Infection Control Practices Advisory Committee should be helpful in reducing
nosocomial legionnaires' disease. Recommendations are in place or are being
developed to minimize the risk of disease in a variety of other settings.
PMID- 9643386
TI - Classification of the genus Legionella.
AB - There are currently 42 described species of legionellae representing 64
serogroups in the family Legionellaceae and the genus Legionella. The phenotypic
characteristics of legionellae are described, including growth requirements, and
biochemical characteristics. Identification of legionellae by biochemical tests,
fatty acid analysis, ubiquinones, protein profiles, carbohydrate analysis,
serology, monoclonal antibodies, and molecular techniques is described. The
occurrence and description of Legionella-like amebic pathogens are discussed. The
problems of identification to the species level are discussed, along with the
need for further evaluations of additional strains from all known species using
biochemical and molecular techniques.
PMID- 9643387
TI - Immunologic response and pathophysiology of Legionella infection.
AB - Legionella pneumophila, the causative agent of legionnaires' disease, is a gram
negative pleomorphic bacillus and fastidious in its growth in artificial medium.
These bacteria grow readily intracellularly, including growth in macrophages and
other phagocytic cells. Humoral antibodies develop readily to these bacteria not
only in infected patients, but also in persons who have had subclinical exposure.
High-levels of serum antibodies may also occur in individuals who recover from
infection. However, cell-mediated immunity based on lymphocytes reacting with the
organisms and cytokines produced by such lymphocytes are important in resistance.
Vaccines prepared from killed Legionella or their components readily induce cell
mediated immunity. Immune resistance to disease depends on lymphocyte-based
immunity, activating cytokine formation, some of which activate macrophages to
resist infection. Resistance to Legionella infection by experimental animals such
as mice correlates with activation of macrophages, which can inhibit replication
of the bacteria. Much recent experimental work has involved studies using inbred
animals, including inbred mice genetically resistant to Legionella versus mice
genetically susceptible. Detailed studies show that regulation of macrophage
resistance versus susceptibility to infection is mediated by specific genetic
mechanisms. Induction of cytokines by Legionella can activate immune cells,
especially helper T cells. Th 1 type helper cells that produce type 1 class
cytokines, such as interferon gamma and interleukin-2 (IL-2), are known to be
important in cellular immunity to Legionella as well as to other opportunistic
intracellular bacteria. In contrast, Th 2 type helper cells, which secrete type 2
class cytokines such as IL-4, IL-5, and IL-6, activate B lymphocytes to produce
humoral antibodies important in resistance to extracellular bacteria which
secrete toxins and extracellular factors as compared to intracellular bacteria
such as Legionella. Although Legionella, similar to other ubiquitous
opportunistic pathogens, can cause serious infection in immunocompromised
individuals, these bacteria have many distinguishing characteristics, such as
very rapid replication in macrophages from susceptible individuals. However,
activated macrophages restrict the growth of these bacteria. Infection by
Legionella, if recognized clinically, can be readily treated with appropriate
antibiotics. Currently, many studies are in progress concerning the mechanism of
pathogenicity and assessment of the molecular biologic mechanisms of protective
immune responses to this bacterium, which causes serious infection in
immunocompromised individuals.
PMID- 9643388
TI - Radiological manifestations of Legionella/Legionella-like organisms.
AB - The chest radiograph of Legionellosis has been described in many reports.
Although some attempted to describe patterns which are specific for Legionella,
in fact, the roentgenographic findings in Legionella infection vary widely and
depend largely on when in the course of illness the radiograph is obtained.
Certain temporal characteristics, however, can serve to enhance the likelihood of
the diagnosis of Legionella pneumonitis. Initial focal infiltrates are most
commonly poorly marginated with 10% presenting with concomitant pleural effusion.
The infiltrates often spread to contiguous lobes eventually becoming bilateral,
with incidence of pleural effusions reaching 35%. This progression often occurs
despite appropriate antimicrobial therapy and often in the face of clinical
improvement. A similar pattern of progression also occurs in immunocompromised
individuals; in addition, a high rate of cavitation and hilar adenopathy is seen
in this subset of patients. A prolonged resolution phase of up to 6 months is
common with rare development of residual densities. Correlating radiographic
features with disease severity and mortality have largely been unsuccessful.
PMID- 9643389
TI - Clinical features of legionnaires' disease.
AB - Legionnaires' disease is a systemic infectious disease primarily involving the
lungs, with multisystemic extrapulmonary manifestations. Any species of
Legionella may cause legionnaires' disease in normal and compromised hosts. The
clinical diagnosis of legionnaires' disease may be made on the basis of
associated extrapulmonary clinical and laboratory findings. Although no single
finding in legionnaires' disease is pathognomonic, the association of key
extrapulmonary constitutes a typical pattern that is diagnostically
characteristic. The syndromic approach based on a weighted point evaluation
system described in the article gives physicians a system to arrive at a rapid
presumptive clinical diagnosis of legionnaires' disease. Definitive diagnosis of
legionnaires' disease is by direct fluorescent antibody testing of respiratory
specimens, serological methods, Legionella urinary antigenuria, or culture.
PMID- 9643390
TI - Legionella and immunosuppression.
AB - Patients with defective immune systems are susceptible to Legionella infection,
especially when the defect involves cell-mediated immunity. Thus, acquired immune
deficiency syndrome (AIDS), corticosteroid administration, and hairy cell
leukemia are risk factors for Legionellosis. Patients who have AIDS may be at
risk for relapsing infections. Corticosteroid administration appears to
predispose patients to simultaneous infection with multiple strains of
Legionellae and development of lung abscess. Legionellosis also is found in
patients who have humoral immune defects, but to a lesser extent. Thus, multiple
myeloma, chronic lymphocytic leukemia, and chronic granulomatous disease have all
been complicated by Legionella infection, although the risk seems to be minimal.
PMID- 9643391
TI - Legionella: a major opportunistic pathogen in transplant recipients.
AB - Legionella have a predilection for infecting immunocompromised patients, and
transplant recipients have the highest risk. Legionella spp have been the most
common cause of nosocomial pneumonia among transplant recipients at selected
medical centers. Diagnosis is dependent on the ability of the clinical
microbiology laboratory to isolate the organism by culture; therefore, the
disease is easily overlooked. The mode of transmission of Legionella pneumophila
is likely aspiration in transplant recipients. Clinical manifestations are
similar to that of other bacterial pneumonias, although diarrhea is often
prominent. The quinolone antibiotics (especially ciprofloxacin) are the
antibiotics of choice because, unlike the macrolides or rifampin, they do not
interact with the immunosuppressive agents used to counter rejection. Prevention
of nosocomial legionellosis involves disinfection of the hospital's potable water
system. Effective disinfection methods include superheat and flush or copper
silver ionization; hyperchlorination is no longer recommended. Routine culture
surveillance directed at the hospital water supply for Legionella is mandatory in
hospitals caring for transplant patients.
PMID- 9643392
TI - Treatment of legionnaires' disease.
AB - Erythromycin has been the most commonly used drug for the treatment of
legionnaires' disease; however, failures have occurred and adverse effects are
common. Doxycycline intravenously is preferred and is less expensive. The newer
macrolides/azalides, clarithromycin and azithromycin, have excellent in vitro
activity against Legionella and fewer adverse effects than erythromycin. The
fluoroquinolones, particularly levofloxacin, are the most active anti-Legionella
antibiotics available. Other agents with activity against Legionella pneumophila
include minocycline, rifampin, and trimethoprim-sulfamethoxazole. The preferred
therapy of legionellosis in immunocompromised patients are quinolone/macrolide
combinations, eg, levofloxacin plus azithromycin.
PMID- 9643393
TI - Disinfection of water distribution systems for Legionella.
AB - Hospital-acquired legionnaires' disease arises from the presence of Legionella in
hospital water systems. Legionella not only persists in hot water tanks but is
also found in the biofilm throughout the entire water distribution system.
Conditions within water systems that promote Legionella colonization include
water temperature, configuration and age of the hot water tank, physicochemical
constituents of the water, plumbing materials, and commensal microflora. Hospital
acquired legionnaires' disease has been prevented by instituting control measures
directed at the water distribution system. These include superheat-and-flush,
copper/silver ionization, ultraviolet light, instantaneous heating systems, and
hyperchlorination. Each of the above disinfection methods has been proven to be
effective in the short-term, but long-term efficacy has been difficult due to
limitations associated with each method. The complexities of Legionella
disinfection, including advantages and disadvantages of each method, are
reviewed. A successful Legionella prevention program requires cooperation and
communication among hospital administrative personnel, engineers, and infection
control staff. Routine environmental surveillance cultures for Legionella are the
critical component for successful long-term disinfection. Culture results
document the efficacy of the disinfection method and alert the hospital staff to
consider Legionella in hospitalized patients with pneumonia.
PMID- 9643394
TI - Diagnostic case study: Rasmussen aneurysm.
PMID- 9643395
TI - Research in progress.
PMID- 9643396
TI - Pregnancy and epilepsy.
AB - Pregnant women with epilepsy are at risk for a variety of complications. This
article reviews the extensive literature on pregnancy and epilepsy with special
emphasis on the management of pregnancy. Information is presented concerning
seizure frequency in pregnancy, effects of epileptic seizures on the fetus,
occurrence of complications during pregnancy and delivery, the incidence of fetal
congenital malformations, and infant development. Recommendations are given
concerning prenatal counseling, antiepileptic drug management, breast feeding,
vitamin K supplementation and folic acid supplementation.
PMID- 9643397
TI - Outborn status with a medical neonatal transport service and survival without
disability at two years. A population-based cohort survey of newborns of less
than 33 weeks of gestation.
AB - OBJECTIVE: Prenatal events are thought to play an important role in long-term
handicap, but the specific role of perinatal factors remains controversial. Our
study, conducted in the context of this debate, aimed to break down the various
components of perinatal management and to assess the relationship between these
components and survival without disability at the age of two years. STUDY DESIGN:
A prospective geographically-defined study was conducted in 1985 in the Paris
metropolitan area. It covered 53430 births (stillbirths and live births),
including 539 that occurred between 25 and 32 weeks gestation. The relationship
between perinatal management and survival without disability was studied by a
multivariate analysis (logistic regression). The analysis was restricted to a
group of 202 infants born at 31 or 32 week's gestation, to avoid indication bias.
RESULTS: An inborn status (delivery in a tertiary care facility) exerted a
protective effect on survival without disability at the age of two years
(Adjusted Odds Ratio (OR)=7.51 [1.51; 37.4]), even though the area we studied
possessed an excellent Medical Neonatal Transport Service. Multiple pregnancies
also seemed to have a protective effect (Adjusted OR=2.45 [0.96; 6.27]). No
statistically significant association was seen between survival without
disability at two years and the presence of a hospital staff paediatrician in the
delivery room. CONCLUSION: These results lead us to consider what the concept of
inborn/outborn represents in the perinatal management of infants at high risk.
PMID- 9643398
TI - Ante- and intrapartum diagnosis of vasa praevia in singleton pregnancies by
colour coded Doppler sonography.
AB - Vasa praevia is a rare complication of pregnancy associated with a high fetal
morbidity and mortality. As planned caesarean section can circumvent fetal risks,
early detection of vasa praevia is desirable. Antenatal diagnosis by ultrasound
by visualisation of vasa praevia may be difficult by transvaginal sonography
alone due to an unfavourable angle of insonation. Combination of transabdominal
and transvaginal sonography is superior in imaging the placental type, location,
insertion of the cord and vasa praevia. We present four cases of antepartum and
one case of intrapartum diagnosis of vasa praevia in singleton pregnancies using
transabdominal and transvaginal colour coded Doppler sonography. A bipartite
placenta with normal cord insertion was found in three cases and with velamentous
insertion of the cord in one case. One case had a partially membranous placenta
with velamentous insertion of the cord. From the site of cord insertion fetal
vessels were coursing over the internal cervical os and then continued in an
amniotic sheet to the main placental mass on the opposite uterine wall.
PMID- 9643399
TI - Umbilical blood flow and neonatal morphometry: a multivariate analysis.
AB - OBJECTIVE: To study the relation between the state of umbilical blood flow and
neonatal morphometry. STUDY DESIGN: We have recorded data from 460 pregnant
women. Umbilical systolic to diastolic ratio was measured within the 3 days prior
to the birth. Weight, height, head and chest circumferences, ponderal and head to
chest circumferences ratio were considered for the study. RESULTS: In a
univariate analysis, the best correlated variable to S/D ratio was the weight (r=
0.35). However, a forward stepwise multiple regression analysis demonstrated that
the best predictors of S/D ratio were height and ponderal index. Small-for
gestational-age fetuses with placental insufficiency (n=20) had a significant
more pronounced decrease of weight, height, head circumference and chest
circumference than those with normal placental perfusion (n=31). The degree of
decrease of ponderal index and HC/TC was similar in both groups. CONCLUSIONS:
Umbilical blood flow is one important factor determining newborn morphometry. If
only one growth variable is considered, the best correlation with umbilical S/D
ratio is found to be the weight. The multivariate regression analysis concluded
that the two most influential factors by umbilical blood flow are height and
ponderal index and the rest of the morphometric parameters lost their significant
correlations when adjusted by these variables. The impairment on neonatal
morphometry in small-for-gestational-age fetuses associated to placental
insufficiency is more severe than that with normal placental perfusion. However,
it does not have a more pronounced decrease of ponderal index than the rest of
causes of small-for-gestational-age fetuses.
PMID- 9643400
TI - Does increased resistance on umbilical artery Doppler preclude a trial of labour?
AB - OBJECTIVE: To determine whether patients with increased resistance on umbilical
artery Doppler velocimetry could be safely allowed a trial of labour. DESIGN: The
Coombe Womens' Hospital is a university teaching hospital which takes tertiary
referrals. All singleton pregnancies found to have increased resistance (>2 SD
above the mean for gestational age) on umbilical artery Doppler ultrasound
between 1993 and 1995 inclusively were identified from the ultrasound database
and reviewed, retrospectively. Cases where the umbilical artery waveform reverted
to normal or deteriorated to absent end diastolic flow on a subsequent scan were
excluded. The 118 cases identified were divided into two groups, those that were
delivered by elective caesarean section and those that laboured. RESULTS: Forty
five patients were delivered by elective caesarean section and 73 were allowed to
labour. In the group that laboured over 90% delivered vaginally and 9.8% were
delivered by emergency caesarean section. Three babies had a cord pH less than
7.20 in the group that laboured. Two babies had an Apgar score of less than 7 at
5 min in the group that were delivered electively. There were no neonatal
seizures or perinatal deaths in either of the two groups. CONCLUSIONS: This study
shows that patients with increased resistance on umbilical artery Doppler can be
allowed a trial of labour without compromising the fetal outcome. We would
suggest that consideration be given to induction of labour in selected patients
as an alternative to elective section.
PMID- 9643401
TI - Application of guidelines for occupational HIV infection control during delivery
in Italy.
AB - OBJECTIVE: We surveyed the attitudes of Italian obstetricians toward the
application of HIV infection control guidelines during labour and delivery
proposed by the Italian National Committee for HIV Infection. STUDY DESIGN: We
identified 66 obstetric centres affiliated to the AOGOI (Association of Italian
Gynecologists and Obstetricians). A postal questionnaire was sent to 752
physicians in charge in the centres. RESULTS: A total of 419 clinicians (55.7%)
completed and returned the form to the coordinating centre. Obstetricians were
directly asked about the need for routine adoption of the Italian guidelines for
delivery of women with positive or unknown HIV status (indicating the routine use
during delivery of protective glasses, impermeable garments, mask and sterile
latex gloves, the washing of hands with detergent solution after using gloves and
collection of needles and sharp instruments in suitable containers). A total of
319 (76.1%) clinicians agreed that all these procedures should be adopted. In
clinical practice, however, obstetricians declared that the use of latex gloves
and collecting needles in suitable containers were always adopted, 'washing hands
after using gloves' less frequently, and other procedures such as protective
impermeable garments, glasses and mask were infrequently applied.
PMID- 9643402
TI - Outcome of 88 pregnancies with absent or reversed end-diastolic blood flow (ARED
flow) in the umbilical arteries.
AB - OBJECTIVES: To investigate both perinatal and postneonatal morbidity and
mortality in fetuses with absent or reversed end-diastolic flow (ARED flow) in
the umbilical artery. STUDY DESIGN: A 5 year prospective follow-up of 88 fetuses
with ARED flow. RESULTS: Sixteen stillbirths, 16 neonatal deaths, six
postneonatal deaths and one death at 2 years of age were noted. Out of the 42
fetuses born alive, 36 showed a normal neurological development whereas six were
mentally handicapped. Adverse prognosis was more frequently found in the group
with absent end-diastolic flow at first examination and then reversed flow until
delivery, compared to the groups of always absent or always reversed end
diastolic flows. CONCLUSIONS: Prompt delivery is recommended in these high-risk
pregnancies in order to prevent long-term sequelae, obviously depending on the
local limits of viability. Further studies appropriately designed for assessing
long-term neurodevelopment of fetuses with ARED flow, although demanding, are
mandatory.
PMID- 9643403
TI - Role of uterine artery Doppler investigation in pregnant women with chronic
hypertension.
AB - OBJECTIVE: To evaluate the role of uterine artery Doppler investigation in
predicting perinatal outcome of patients with chronic hypertension. STUDY DESIGN:
Uterine artery velocimetry was investigated at 24 weeks gestation in 78 chronic
hypertensive pregnant women by means of color Doppler. The resistance index (RI)
and the presence of a diastolic notch were recorded and related to the
development of superimposed preeclampsia (SPE), pregnancy aggravated hypertension
(PAH). and intrauterine growth retardation (IUGR). RESULTS: There were more
pregnancy complications in the 25 patients with abnormal RI, compared with the 53
women with normal RI (SPE 12% vs. 0%, PAH 36% vs. 7% and IUGR 52% vs. 2%;
P<0.01), and more in women with a bilateral diastolic notch compared with those
without (SPE 23% vs. 0, PAH 54% vs. 4%, IUGR 85% vs. 2%; P<0.0001), while no
differences were detected in those with only a unilateral notch, except for PAH
(27% vs. 4%; P<0.01). CONCLUSION: Uterine artery Doppler velocimetry identifies a
subgroup of chronic hypertensive patients with a high frequency of pregnancy
complications.
PMID- 9643404
TI - Women attending human immunodeficiency virus counselling and testing site because
of pregnancy, and prevalence of newly diagnosed infections.
AB - To evaluate the trend of and the reason for women attending HIV counselling and
testing (CT) because of pregnancy or pregnancy planning, and the observed human
immunodeficiency virus (HIV) prevalence rate, systematic data was gathered during
free pre- and posttest discussion, at a major CT site of Rome, Italy, from July
1985 to June 1996. A total of 3608 women were enrolled, increasing from 0.9% of
the total number of female clients in 1986 to 34.6% in 1996. Most women (92.5%)
were referred by gynaecologists, mostly without reported risk factors for HIV
infection. In 22.5% of cases the test was performed after the first trimester of
pregnancy. Prior tested women increased significantly from 6.7% in 1989 to 33.4%
in the first half of 1996. Two thirds of women reported their current partners
were not tested for HIV. Thirteen (0.36%) newly diagnosed women were observed;
four were not aware of being at risk. In Italy HIV testing seems to have been
included as a part of routine prenatal care. Efforts should be made to optimise
the period when testing is performed. Universal counselling and testing of the
couple could be the appropriate way to recognise most cases of newly diagnosed
HIV infection.
PMID- 9643405
TI - Confidential enquiry into maternal deaths in The Netherlands 1983-1992.
AB - OBJECTIVE: To determine the causes of maternal death in The Netherlands. STUDY
DESIGN: Nationwide Confidential Enquiry into the Causes of Maternal Deaths during
the period 1983-1992. RESULTS: Of 192 direct and indirect maternal deaths, 154
(80%) were available for the Enquiry. The most frequent direct causes were (pre
)eclampsia, thrombo-embolism, obstetrical haemorrhage and sepsis. Cerebro- and
cardiovascular disorders were the most frequent indirect causes of death. Age
above 35 years and parity 3 or more are related to higher maternal mortality.
Women from non-caucasian origin are more prone to death in comparison to
caucasian women. Autopsy was performed in 88 cases (57%). Of the 24 women where
labour started at home, the place of birth played a significant role in delay in
four. CONCLUSIONS: More efforts should be made to have a higher percentage than
80% available for the Confidential Enquiry as in the UK where only 1-4% of deaths
are not available for similar purposes. Also, the autopsy rate of 57% is much
lower than in the UK (82%). Special strategies should be developed to improve
maternal health of populations at higher risk such as women of high age and
parity and immigrant populations.
PMID- 9643406
TI - Thermal balloon endometrial ablation: safety aspects evaluated by serosal
temperature, light microscopy and electron microscopy.
AB - OBJECTIVES: Thermal balloon endometrial ablation is a new method for treating
menorrhagia. The technique appears to be less difficult compared to standard
hysteroscopic ablation techniques and to be significantly safer. The influence
into the uterine wall of the thermal balloon ablation procedure was investigated
with special reference to the ability of total destruction of the endometrium and
the thermal action on the myometrium and the serosa. STUDY DESIGN: Temperatures
were measured at the uterine serosal surface during thermal balloon endometrial
ablation for 8-16 min in eight patients. After subsequent hysterectomy the extent
of thermal damage into the myometrium was assessed by light and electron
microscopy. RESULTS: The highest temperature measured on the uterine serosa was
39.1 degrees C. Coagulation of the myometrium adjacent to the endometrium could
be demonstrated by light microscopy in all patients, with a maximum depth of 11.5
mm. By electron microscopy no influence of heat could be demonstrated beyond 15
mm from the endometrial surface. CONCLUSION: Up to 16 min of thermal balloon
endometrial ablation therapy can destroy the endometrium and the submucosal
layers. The myometrium is only coagulated to a depth where full thickness
necrosis or injury is unlikely.
PMID- 9643407
TI - Uterine papillary serous carcinoma: study of 19 cases.
AB - OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an uncommon highly
malignant variant of endometrial carcinoma that histologically and clinically
resembles ovarian papillary serous carcinoma. The purpose of this study was to
present the conjoined experience of two regional hospitals in the south of Israel
(Soroka Medical Center, Beer-Sheva and Kaplan Hospital, Rehovot) of handling this
tumour. STUDY DESIGN: Data from the files of 19 patients with UPSC who were
managed at these hospitals between July 1991 and June 1997 were evaluated.
RESULTS: The three-year survival rate was 57.3% overall; 83.3% for Stage I and
21.2% for Stages II, III, and IV combined (P<0.02). Eighteen patients had primary
surgery which included total abdominal hysterectomy and bilateral salpingo
oophorectomy and 15 (83.3%) of them received postoperative adjuvant therapy which
included radiotherapy and/or systemic chemotherapy. CONCLUSIONS: The prognosis of
patients with UPSC is worse than that of patients with other forms of endometrial
carcinoma. Primary surgery comprised of total abdominal hysterectomy, bilateral
salpingo-oophorectomy and staging is the mainstay of treatment. The type of
postoperative treatment is not consistent. By and large, adjuvant pelvic
radiotherapy is usually given in early-stage disease and adjuvant systemic
chemotherapy is usually prescribed in advanced-stage disease.
PMID- 9643408
TI - Estrogen and postmenopausal estrogen/progestin therapy: effect on endothelium
dependent prostacyclin, nitric oxide and endothelin-1 production.
AB - It is well documented that postmenopausal estrogen/progestin therapy (HRT)
protects women against cardiovascular disorders. However, the mechanism(s) by
which this protection is mediated remains largely unresolved, because beneficial
effects of estrogen on the blood lipid profile account for only 20-30% of the
overall protection. Growing evidence suggests that estrogen has direct effects on
the blood vessel wall indicating that vascular endothelium may play a key role in
mediating these effects by producing vasoactive factors, such as prostacyclin
(PGI2), nitric oxide (NO) and endothelin-1 (ET-1). In vitro estrogen stimulates
endothelial PGI2 and NO production, whereas ET-1 production is not affected.
Moreover, in vivo studies indicate that estrogen and HRT increase PGI2 and NO
production, whereas ET-1 production decreases. These effects are evidently
mediated through estrogen receptors in endothelial cells. Thus, estrogen and HRT
lead to the dominance of vasodilatory and antiaggregatory agents released by the
endothelial cells. This may be an important new mechanism in the cardiovascular
protection mediated by estrogen and HRT.
PMID- 9643409
TI - Conservation of the follicular population in irradiated rats by the
cryopreservation and orthotopic autografting of ovarian tissue.
AB - AIM: To preserve the follicular population in rats prior to abdominal irradiation
by the orthotopic autografting of ovarian cortical slices (frozen/thawed) in one
of two cryoprotective agents (CPAs). The proportion of follicular survival will
be quantified at autopsy and a comparison will be made of the two CPAs. METHOD:
Thirty Wistar rats, aged 38-39 days, were unilaterally ovariectomised. The
ovaries of twenty animals were slow-cooled in either 1.5 M dimethylsulphoxide
(DMSO; group B) or 1.5 M ethylene glycol (EG; group C). The ovaries of the
remaining ten animals (group A) were fixed and histologically examined to
determine a fresh follicle count. The contralateral ovary was irradiated with a
single dose of 2.5 Gy. Frozen tissue (from groups B and C) was thawed rapidly and
autografted into the irradiated ovarian bursa. All animals were mated eighteen
days after grafting and were sacrificed eighteen days later. At autopsy, the
number of embryos was counted and the ovarian weights recorded, before the tissue
was prepared histologically for quantification of follicular survival. RESULTS:
There was no significant difference in the pregnancy rate in the three groups
and, although there was a higher number of embryos in the irradiated control
group A compared with groups B and C, the difference was not significant. The
follicle count in groups B and C was significantly higher than in group A. In
group A, the percentage of growing follicles was higher than in groups B and C
and the fresh ovary. CONCLUSIONS: Autografting frozen/thawed ovarian tissue
preserved a proportion of the follicular population in irradiated rats. There was
no significant difference in the numbers of follicles surviving cryopreservation
in the two CPAs. Since the irradiated rats were not totally sterilised, we cannot
conclude that cryopreserved grafts can restore fertility.
PMID- 9643410
TI - Cervical pregnancy managed by suction evacuation and balloon tamponade.
AB - A woman with a very poor obstetric history with a cervical pregnancy was managed
without hysterectomy. Diagnosis was made by the transvaginal ultrasound.
Haemorrhage was controlled by suction evacuation and balloon tamponade. Although
cervical perforation occurred, the tamponade was able to control haemorrhage
after repair of the perforation.
PMID- 9643411
TI - Delayed recognition of major vascular injury during laparoscopy.
AB - We report an unusual case of left common iliac artery and vein injury during
laparoscopy. The injury was recognized 3 h after the completion of the
laparoscopy. The patient was promptly treated by explorative laparotomy and
repair of the lacerated vessels. Major vascular injury during laparoscopy is
usually caused by the Verres needle or the first laparoscopic trocar. Failure to
recognize the injury during the laparoscopic procedure itself can be attributed
to the intraperitoneal CO2 pressure compressing the bleeding vessels and to the
decreased venous return caused by the steep Trendelenburg position. Major
vascular injury should be recognized as early as possible since it is a life
threatening condition that necessitates immediate and prompt treatment.
PMID- 9643412
TI - Non-Hodgkin's lymphoma during pregnancy--case report.
AB - Occurrence of Non Hodgkin's lymphoma (NHL) in pregnancy is very rare. A 24-year
old woman with NHL stage IVB complicating pregnancy is presented. The diagnosis
was made by biopsy at 27 weeks. The patient received combination chemotherapy
which led to remission of the disease. The baby was delivered by an emergency
caesarean section, due to fetal distress at 31 weeks. Unfortunately after a short
period of remission a relapse occurred and magnetic resonance imaging (MRI)
showed cerebral involvement, indicating a poor prognosis. She died seven months
later from disseminated disease.
PMID- 9643413
TI - Congenital cystic adenomatoid malformation of the lung and fetal hydrops--a case
with favourable outcome.
AB - We present a case of congenital cystic adenomatoid malformation of the lung
(CCAM) diagnosed at 23 weeks of gestation with concomitant fetal hydrops. The
sonographical picture of CCAM disappeared in the third trimester of pregnancy and
fetal hydrops resolved under medication with digitalis to the mother. The neonate
showed mild dyspnea; the prenatal diagnosis of CCAM was confirmed by chest X-ray
and computed tomography. The affected lung segments were dissected at 5 days of
age. The diagnosis of CCAM type III was confirmed histologically.
PMID- 9643414
TI - Chorioangioma of the placenta in association with early severe polyhydramnios and
elevated maternal serum HCG: a case report.
AB - We report a case of a chorioangioma of the placenta which was associated with
elevated maternal serum HCG in the second trimester, severe early polyhydramnios
and premature delivery. Chorioangioma should be considered in the differential
diagnosis of an elevated HCG observed as part of the triple test.
PMID- 9643415
TI - Discordant prenatal diagnosis of congenital toxoplasmosis in a dizygotic
pregnancy.
AB - Prenatal diagnosis of toxoplasmosis gondii in twin pregnancies has been described
twice. In both cases they were accomplished by prenatal blood sampling of the
foetuses. We report the first prenatal diagnosis with a discordant result in a
dizygotic pregnancy. One of the foetuses died in utero and the other was born
unaffected at term.
PMID- 9643416
TI - Renal venous thrombosis: an unusual cause of fetal distress.
AB - Renal venous thrombosis (RVT) is a rare event in neonates and infants. Its
incidence varies from 0.5 per thousand concerning admissions in neonatal
intensive care units to 0.5% in autopsic findings. Some cases may occur in the
antenatal period. Clinical presentation in infants includes a mass in the flank.
hematuria and thrombocytopenia. We report a case of RVT which was diagnosed at 34
weeks' gestation by ultrasound in a fetus showing cardiotocographic signs of
fetal distress. We observed the typical pattern reported by pediatric
radiologists: renal enlargement, loss of the cortico-medullary boundary, echoic
streaks following the direction of interlobular veins, lack of definition of
renal sinus echoes and loss of venous flow in the right kidney by Doppler
velocimetry. After delivery by caesarean section and transient hyperbilirubinemia
and moderately impaired renal function the infant weighing 2435 g had a full
recovery at 1 week and a normal evolution at 1 month of life.
PMID- 9643417
TI - The identification of myogenic cells in skeletal muscle, with emphasis on the use
of tritiated thymidine autoradiography and desmin antibodies.
AB - The identification of myogenic precursor cells (mpc) is a key factor in
determining the early events in the myogenesis and regeneration of skeletal
muscle. Although satellite cells have long been established as the providers of
myoblastic cells, very little is really known (apart from their anatomical
location in relation to muscle fibres and their ability to migrate) about the
precise role of satellite cells in myogenesis. Numerous techniques for labelling
mpc have been devised, but none of these has proven to be completely reliable in
firmly establishing the origin of myogenic cells. The use of tritiated thymidine
to label DNA in proliferating mpc (which are not specifically distinguishable at
the time) and the subsequent location of their labelled progeny in myotube nuclei
has revealed a great deal of data on the timing of myogenesis, but not about the
nature of mpc themselves. DNA synthesis can also be detected by antibodies to the
thymidine analogue, bromodeoxyuridine, and also by antibody staining for
proliferating nuclear cell antigen. Like tritiated thymidine, these other markers
are not specific for muscle but are general markers for DNA synthesis. In situ
hybridisation of various muscle-specific genetic markers and their products has
been informative, as has immunolabelling of myogenin, MyoD1 and desmin. Desmin
labelling has been particularly instructive in identifying mpc because it is one
of the first muscle-specific proteins to be produced in mpc. This review covers
some of the techniques mentioned above and their usefulness in determining the
early events in myogenesis.
PMID- 9643418
TI - Differentiation of the epidermis during scale formation in embryos of lizard.
AB - The formation of the first epidermal generations and in particular of the
shedding complex in the developing scales of the lizards Anolis lineatopus and
Podarcis muralis was studied by electron microscopy. The initially linear and
bilayered epidermis turned into symmetric papillae, which became asymmetric
scales. The outer periderm was more electrondense than the following layer,
provisionally named 'inner periderm' but probably derived from the basal layer.
Coarse thick filaments progressively filled the cytoplasm of the inner periderm
or formed reticulate bodies resembling avian peridermal granules. Peridermal
cells cornified slightly and could be shed in ovo. From the basal layer various
suprabasal epithelial layers were produced. The first layer contained
keratohyalin-like granules and was identified as a clear layer. Beneath it a
spinulated (Anolis) or serrated (Podarcis) oberhautchen differentiated. The clear
and 'oberhautchen' layers constitute the first shedding complex. The first
epidermal layers that were shed consisted of flaking periderm or periderm
together with the clear layer. The differentiation of a mesos layer was under way
before hatching, when the epidermal morphology resembled a stage 4-5 of the adult
shedding cycle. Fibroblasts under the inner side of the scale made few contacts
with the basement membrane and their cytoplasmic elongations were mostly oriented
parallel to the dense lamina. Instead, fibroblasts under the basal layer of the
outer scale surface (BLOS) made numerous contacts with the basement membrane,
suggesting that more dermal-epidermal interactions take place on this side of the
scale.
PMID- 9643419
TI - Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in
hairless mouse skin in vivo.
AB - Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of
the skin of hairless mice in vivo. Application of acridine orange enabled imaging
of the layers of the epidermis. The corneocytes of the stratum corneum, the
keratinocytes in the basal layers and redundant hair follicles were visualised at
depths greater than 100 microm. Cellular and nuclear membranes of keratinocytes
of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging
of the skin after injection of FITC-dextran revealed an extensive network of
blood vessels with a size range up to 20 microm. Blood cells could be seen moving
through dermal vessels and the blood circulation through the dermal vascular bed
was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves
fibres around the hair follicles and subsurface blood vessels. Comparison was
made between images obtained in vivo using FOCI and in vitro scanning electron
microscopy and conventional histology. FOCI offers the potential to study dynamic
events in vivo, such as blood flow, skin growth, nerve regeneration and many
pathological processes, in ways which have not previously been possible.
PMID- 9643420
TI - Pancreatic endocrine cells in Bufo bufo: immunocytochemistry and ultrastructure.
AB - The endocrine pancreas of the toad consists of rounded islets of various sizes
embedded in the exocrine tissue. Isolated cells are also present. At least 4
types of endocrine cell are distinguishable by shape, size and electrondensity of
the secretory granules as well as by their immunoreactivity with different
antisera: insulin, somatostatin, pancreatic polypeptide, and glucagon cells.
Insulin cells can be divided into 2 types according to their cytoplasmic
electrondensity. Colocalisation of different hormones in the same cell is rarely
observed. The close contact between endocrine and exocrine cells and the scarcity
of nerve supply is indicative of a paracrine control of hormone secretion.
PMID- 9643421
TI - Muscle fibre types and their distribution in the biceps and triceps brachii of
the rat and rabbit.
AB - Muscle fibre type composition and distribution in the biceps brachii (long head)
and triceps brachii (long head) of the rat and rabbit were investigated using the
following histochemical techniques: myosin ATPase, with preincubation at pH 10.4
and 4.35; succinate dehydrogenase (SDH) and glycogen phosphorylase. The muscle
fibres were classified into slow-twitch (SO), fast-twitch glycolytic (FG), fast
twitch oxidative glycolytic (FOG and FOg) and fast-twitch oxidative fibres (FO).
Significant differences in the regional distribution of muscle fibre types have
been observed between the rat and the rabbit. In the rat, SO fibres were
restricted to the deep regions of both biceps and triceps brachii, whereas FG
fibres were located in the intermediate and superficial regions (the superficial
regions contained the highest percentages of FG fibres). In the rabbit, SO and FG
fibres were spread over the entire muscle, although SO and FG fibres were most
abundant in the deep and superficial regions respectively. These findings
indicate that the biceps and triceps brachii are more regionalised in the rat
than in the rabbit.
PMID- 9643422
TI - Comparative skeletal muscle fibre morphometry among wild birds with different
locomotor behaviour.
AB - Six muscles of the mallard duck (Anas platyrhynchos), the common coot (Fulica
atra) and the yellow-legged gull (Larus cachinnans) were analysed
morphometrically, with special emphasis on their functional implications and
physiological needs. Oxidative fibres always had significantly smaller size than
anaerobic fibres, although no differences in the number of capillaries per fibre
were found. This resulted in greater capillary counts per unit of fibre area and
perimeter in oxidative than anaerobic fibres, which indicates that the greater
demand for oxygen supply may be achieved by decreasing the size of the muscle
fibre rather than by increasing the number of associated capillaries. Fast
oxidative fibres of the pectoralis and the triceps of the gull had greater sizes
than the fast oxidative fibres of the mallard and the coot, which correlates with
the difference in energetic demands between flapping and gliding flight. Greater
fibre cross-sectional areas and perimeters seem suited to afford the long-lasting
activity with low metabolic demands required during gliding. By contrast,
mallards and coots attain a high oxidative metabolism, during sustained flapping
flight, by reducing fibre size at the expense of a diminished ability for force
generation. Between-species comparisons of the hindlimb muscles only yielded
differences for the anaerobic fibres of the gastrocnemius, as an important
adaptive response to force generation during burst locomotion. The need to manage
sustained swimming abilities effectively may result in similar FOG fibre
morphometry of the hindlimb muscles studied, indicating that a compromise between
the oxygen flux to the muscle cell and the development of power is highly
optimised in oxidative fibres of the bird species studied.
PMID- 9643423
TI - Immunofluorescent localisation of tumour necrosis factor-alpha receptors on the
popliteal lymph node and the surrounding adipose tissue following a simulated
immune challenge.
AB - We used immunohistochemical techniques to demonstrate the distribution of
receptors for the cytokine tumour necrosis factor-alpha on the popliteal lymph
node and the adipose tissue surrounding it for 5 d following a simulated immune
challenge to one hind leg in the rat. We found different patterns of expression
of receptors on adipocytes surrounding a lymph node to a distance of about 1 mm,
and on those more remote from the node. Sites recognised by an antibody to type I
tumour necrosis factor receptors appeared on the challenged node and the
adipocytes surrounding it within 30 min of an injection of bacterial
lipopolysaccharide, but appeared on adipocytes surrounding the unchallenged
popliteal node only 24 h later. Adipocytes distant from the node, both within the
same depot and in the contralateral depot, showed no response. Sites recognised
by an antibody to type II tumour necrosis factor receptors were present at all
times on lymph nodes and the adipocytes close to them, but appeared on more
distant adipocytes only 24 h after immune challenge, in both challenged and
unchallenged legs. These data support the proposal, based on in vitro studies,
that the adipose tissue surrounding major lymph nodes is specialised to respond
to cytokines derived from lymphoid cells, and participates in the immune
responses of the adjacent node.
PMID- 9643424
TI - Variation in the apparent density of human mandibular bone with age and dental
status.
AB - This study examines the variability in the anatomy of mandibles of differing ages
and different stages of tooth loss. Mandibles from individuals between 19 and 96
y were sectioned into 2 mm thick vertical plane-parallel slices and cleaned of
marrow and periosteum. The apparent density (mass per unit volume in g/ml) from
midline (MID) and mental foramen region (MF) sites was determined by weighing the
slices and dividing by a volume calculated as the product of section thickness
and the mean area of the 2 sides of the section. The cortical thickness of the
inferior border and the basal and alveolar bone heights were measured in
radiographs of the slices. Mandibular apparent density was negatively correlated
with the cross sectional area (midline r=-0.48, mental foramen r=-0.45), and at
the midline was significantly greater in edentulous than in dentate individuals
(means (+/-S.E.M.) edentulous n=13: 1.43 (+/-0.07) g/ml; dentate n=17: 1.27 (+/
0.04) g/ml, P < 0.05). Where a large enough age range was available, mandibular
apparent bone density showed a significant increase with age (midline males:
r=0.53, n=18) especially for dentate individuals (r=0.91, n=8). There was a
correlation between the apparent densities at the two sites in the same mandible
(r=0.64), with the values obtained for the midline being significantly greater
than for the mental foramen region (midline 1.34 (+/-0.04) g/ml; mental foramen
1.19 (+/-0.04) g/ml, P < 0.001, paired t test). The mandible shows great
interindividual variability, but there may be a considerable reduction in cross
sectional girth of the mandible following tooth loss, and, unlike postcranial
sites, an increase in apparent density with age.
PMID- 9643425
TI - Mineralisation density of human mandibular bone: quantitative backscattered
electron image analysis.
AB - This study examined the tissue level mineralisation density distribution in
mandibles from 88 adult humans. Mandibles (19-96 y) were sectioned vertically in
midline (MID), mental foramen (MF), and third molar (M3) regions. Surgical
fragments from M3 were obtained from individuals aged 16-38 y. All specimens were
cleaned, embedded in PMMA, micromilled and examined by digital 20 kV
backscattered electron (BSE) stereology. Quantitation was based on rescaling
image histograms to the signal range between a monobrominated (0) and a
monoiodinated (255) dimethacrylate resin standard. Mineralisation density
increased with age (r=0.70; P < 0.0001): the mean for 39 individuals aged between
16 and 50 y was significantly lower (P < 0.0001) than for 35 individuals over 51
y (mean (+/-S.E.M.): 158.20 (1.63) and 174.71 (1.27) normalised grey level units
respectively). There was good correlation in mean mineralisation density between
different sites in the same mandible, but MID was significantly less highly
mineralised than the other sites: MID 173.90, MF 177.34, M3 177.11 (P < 0.002 and
0.01 for MF and M3 respectively; paired t test), as was the alveolar bone density
when compared with the bone of the inferior cortex (e.g. MID: 171.13 (1.53) and
174.46 (1.14) P < 0.0001). No sex difference was found. Partially dentate
mandibles generally had regions of higher mineralisation than fully dentate and
edentulous mandibles. The lowest density bone occurred at the alveolar crest
anteriorly and superolingually at M3, matching sites of net resorption following
tooth loss. Highest densities were found inferolingually at MID, inferiorly at MF
and buccally at M3, matching the sites thought to experience the highest
functional strains. This stresses the importance that local factors may have in
the remodelling of the edentulous mandible. Morphology showed that there is a
preponderance of highly mineralised cement lines, and of packets containing dead,
mineralised, osteocytes.
PMID- 9643426
TI - The organisation of the enteric nervous system in the submucous and mucous layers
of the small intestine of the pig studied by VIP and neurofilament protein
immunohistochemistry.
AB - The arrangement of the enteric ganglia and nerve fibre plexuses was examined in
the submucous and mucous layers and around Peyer's patches of the porcine small
intestine to clarify their organisation. Immunohistochemistry of vasoactive
intestinal peptide (VIP) and neurofilament proteins in wholemounts, chopped or
paraffin sections was used to locate the neural elements. The ganglia of the
internal and external submucous plexuses were situated at 2 different topographic
locations, being clearly demarcated by the submucosal vascular arcades and
differing in neuronal composition. The internal submucous plexus was the only
contributor to the plexus surrounding the follicles of Peyer's patches as a
continuous mesh of 3 ganglionated nerve subplexuses. VIP-immunoreactive fibres
from this mesh innervated the dome. The mucosal plexus, which was subdivided into
4 subunits--the outer proprial, inner proprial, pericryptal and villous plexuses-
contained a few solitary neuronal perikarya. Labelling for neurofilament proteins
revealed Dogiel types II, IV and VI neurons. The observations reveal several new
features in the enteric nervous system of the pig and clarify its nomenclature.
PMID- 9643427
TI - Cartilaginous development of the human craniovertebral junction as visualised by
a new three-dimensional computer reconstruction technique.
AB - Serial transverse histological sections of the human craniovertebral junction
(CVJ) of 4 normal human embryos (aged 45 to 58 d) and of a fetus (77 d) were used
to create 3-dimensional computer models of the CVJ. The main components modelled
included the chondrified basioccipital, atlas and axis, notochord, the
vertebrobasilar complex and the spinal cord. Chondrification of the component
parts of CVJ had already begun at 45 d (Stage 18). The odontoid process appeared
to develop from a short eminence of the axis forming a third occipital condyle
with the caudal end of the basioccipital. The cartilaginous anterior arch of C1
appeared at 50-53 d (Stages 20-21). Neural arches of C1 and C2 showed gradual
closure, but there was still a wide posterior spina bifida in the oldest
reconstructed specimen (77 d fetus). The position of the notochord was constant
throughout. The normal course of the vertebral arteries was already established
and the chondrified vertebral foramina showed progressive closure. The findings
confirm that the odontoid process is not derived solely from the centrum of C1
and that there is a 'natural basilar invagination' of C2 during normal embryonic
development. On the basis of the observed shape and developmental pattern of
structures of the cartilaginous human CVJ, we suggest that certain pathologies
are likely to originate during the chondrification phase of development.
PMID- 9643428
TI - Patterns of sexual, bilateral and interpopulational variation in human femoral
neck-shaft angles.
AB - Data on femoral neck-shaft angles were collected for 30 modern, historic and
prehistoric human population samples, and analysed with respect to sexual
dimorphism, bilateral asymmetry, geographical patterning and general economic
level. Although some samples had modest sexual dimorphism in this angle, and some
individuals exhibited clear asymmetry, there were no consistent patterns of
sexual or side differences across human populations. Similarly, there was no
evidence for geographic differences, since broad regional groups lacked
significant differences and mean angles were not correlated with latitude.
However, there is a significant increase in mean neck-shaft angles across
populations with an increasingly sedentary existence and with mechanisation. The
last reflects the developmental plasticity of this feature with respect to
habitual load levels during ontogeny of the hip region.
PMID- 9643429
TI - Squatting facets on the neck of the talus and extensions of the trochlear surface
of the talus in late Byzantine males.
AB - Remodelling of bone occurs in response to physical stress. Habitual squatting is
associated with modifications of the neck of the talus (squatting facets) and its
trochlear/malleolar surfaces (trochlear extensions), and individual populations
exhibit different incidences of these modifications that reflect their lifestyle.
The occurrence of talar modifications was therefore investigated in a population
of late Byzantine (13th century AD) adult male skeletons. Lateral squatting
facets occurred most frequently (37.7%), but medial (0.6%), combined (0.6%) and
continuous (gutter-like) facets (0.6%) were also observed. Lateral (8.0%), medial
(10.9%) and continuous (lateral/central/medial) extensions (4.6%) of the
trochlear surface were all present in the late Byzantine population. There was no
evidence of side dimorphism. The occurrence of lateral squatting facets in the
late Byzantine population was greater than that reported for modern Europeans,
but similar to that reported for some populations of modern Indians. The
frequency of occurrence of trochlear extensions in the late Byzantine population
was substantially less than in modern Indian populations, but similar to modern
Europeans. Therefore, it is unlikely that precisely the same factors determine
the expression of squatting facets and trochlear extensions.
PMID- 9643430
TI - Distribution of lymphoid tissue in the caecal mucosa of chickens.
AB - In order to clarify the fundamental structure of the host defence mechanism in
chicken caeca, a detailed analysis of the distribution of lymphoid nodules (LNs)
was carried out on longitudinal sections of both the mesenteric (side of the
ileocaecal ligament) and the antimesenteric mucosa. An overwhelming majority of
solitary or aggregated LNs were located in the mesenteric mucosa, although a few
were also found in the antimesenteric mucosa. Of the total LNs, 45.7% were
detected at the proximal 7.8% section in the caecal tonsil. LNs (21.4%) were also
concentrated in the distal 22.0% section corresponding to the apex. A moderate
concentration of LNs (13.1%) was found at the transitional 20.0% region between
the base and body. Approximately 80.2% of total LNs were found at the above 3
regions in the mesenteric mucosa. In many cases, the frequency of LNs in the
caecal tonsils was opposite to that at the apices. Aggregated LNs were mainly
found in the caecal tonsils, transitional region and apex. Almost all aggregated
LNs consisted of fundamental nodular units possessing M cells in their follicle
associated epithelia. The aggregated LNs in the above 3 regions therefore could
provide immunological surveillance against caecal luminal contents. In
particular, the cooperative function between LNs of the caecal tonsil and apex
might be highly important in maintaining the caecal microenvironment.
PMID- 9643431
TI - Postscript on possum cartilage and oxygen; what is keratan sulphate? A
corrigendum to the addendum.
PMID- 9643432
TI - Two rare anomalies of the brachial plexus.
PMID- 9643433
TI - Teaching of gross anatomy to medical undergraduates: general practice as a
guideline? A synopsis.
PMID- 9643434
TI - An anomalous muscle in the region of the popliteal fossa: case report.
PMID- 9643435
TI - Morphology of the articular processes of the sixth cervical vertebra in humans.
PMID- 9643436
TI - Chitosan-EDTA conjugate: a novel polymer for topical gels.
AB - A recently developed chitosan-EDTA conjugate, neutralized with sodium hydroxide
(NaChito-EDTA), has been tested for possible topical use. The technical
properties and microbial stability of NaChito-EDTA have been compared with those
of carmellose sodium (NaCMC), hydroxypropylmethylcellulose (HPMC), sodium
polycarbophil (NaPCP) and sodium carbopol 980 (NaC980), well established
gelatinizing agents. NaChito-EDTA forms stable, colourless, completely
transparent hydrogels at a polymer concentration of 0.5%. Of the polymers tested
the novel polymer had the lowest incompatibility with multivalent cations and
with ethanol, and much the best swelling properties. After 28 days of incubation
at room temperature the rates of growth of the complete bacterial spectrum
occurring in demineralized water and of Escherichia coli, serving as model strain
representative of gram-negative bacteria, were at least 2 log and 5.7 log,
respectively, lower in NaChito-EDTA gels than in the other hydrogels. This
antimicrobial activity of NaChito-EDTA can be explained by its highest binding
affinity towards magnesium, which stabilizes the outer membrane of gram-negative
bacteria. However, this antimicrobial effect is insufficient to guarantee
microbial stability. Further results showed that the antimicrobially acting
polypeptide nisin can be recommended as an alternative novel preservative for
NaChito-EDTA gels, because its antimicrobial spectrum could also be increased
towards gram-negative bacteria in combination with chelating excipients. NaChito
EDTA seems, therefore, to be a promising novel polymer for topically-used gels,
with advantages over well established gelatinizing agents.
PMID- 9643437
TI - Polymeric chitosan-based vesicles for drug delivery.
AB - A simple carbohydrate polymer glycol chitosan (degree of polymerization 800
approx.) has been investigated for its ability to form polymeric vesicle drug
carriers. The attachment of hydrophobic groups to glycol chitosan should yield an
amphiphilic polymer capable of self-assembly into vesicles. Chitosan is used
because the membrane-penetration enhancement of chitosan polymers offers the
possibility of fabricating a drug delivery system suitable for the oral and
intranasal administration of gut-labile molecules. Glycol chitosan modified by
attachment of a strategic number of fatty acid pendant groups (11-16 mol%)
assembles into unilamellar polymeric vesicles in the presence of cholesterol.
These polymeric vesicles are found to be biocompatible and haemocompatible and
capable of entrapping water-soluble drugs. By use of an ammonium sulphate
gradient bleomycin (MW 1400), for example, can be efficiently loaded on to these
polymeric vesicles to yield a bleomycin-to-polymer ratio of 0.5 units mg(-1).
Previously polymers were thought to assemble into vesicles only if the polymer
backbone was separated from the membrane-forming amphiphile by a hydrophilic side
arm spacer. The hydrophilic spacer was thought to be necessary to decouple the
random motion of the polymer backbone from the ordered amphiphiles that make up
the vesicle membrane. However, stable polymeric vesicles for use in drug delivery
have been prepared from a modified carbohydrate polymer, palmitoyl glycol
chitosan, without this specific architecture. These polymeric vesicles
efficiently entrap water-soluble drugs.
PMID- 9643438
TI - N-acetyl-L-gamma-glutamyl derivatives of p-nitroaniline, sulphamethoxazole and
sulphamethizole for kidney-specific drug delivery in rats.
AB - Kidney-specific delivery of p-nitroaniline, sulphamethoxazole and sulphamethizole
after either intravenous administration of the L-gamma-glutamyl or N-acetyl-L
gamma-glutamyl derivatives or the parent drugs has been examined in a rat model.
All L-gamma-glutamyl derivatives were converted to the corresponding parent drugs
within 60 min whereas the N-acetyl-L-gamma-glutamyl derivatives were fairly
stable in the systemic circulation after parenteral administration.
Concentrations of p-nitroaniline and sulphamethoxazole 20 min after
administration of the parent drugs were somewhat higher in the kidney than in the
liver and lung. The concentration of sulphamethizole in the kidney was
dramatically higher than those in the hepatic and pulmonary tissue. Kidney
specific delivery of the drugs of interest was evaluated by determining the
tissue concentrations of the released parent drug and the total drug levels (i.e.
drug levels after hydrolysis of all conjugate to the parent drug). For L-gamma
glutamyl-p-nitroaniline released renal levels of p-nitroaniline and total p
nitroaniline concentrations were both higher than those obtained after p
nitroaniline dosing. Use of L-gamma-glutamylsulphamethoxazole resulted in higher
total sulphamethoxazole concentrations in the kidney, but did not lead to an
increase in released (unconjugated) sulphamethoxazole levels. In contrast, no
kidney-selective distribution was observed for L-gamma-glutamylsulphamethizole.
Markedly increased kidney distribution was observed for both N-acetyl-L-gamma
glutamyl-p-nitroaniline and N-acetyl-L-gamma-glutamylsulphamethoxazole and the
liver and lung concentrations were correspondingly reduced in comparison with
parent drug dosing. Use of the N-acetyl-L-gamma-glutamyl-p-nitroaniline conjugate
increased the concentration of p-nitroaniline in the kidney to the same extent as
did L-gamma-glutamyl-p-nitroaniline. In conclusion, N-acetyl-L-gamma-glutamyl
derivatization of certain compounds seems to be useful for kidney-specific drug
delivery and preliminary data suggests that lipophilic drugs are better
substrates than hydrophilic compounds. Results related to the selectivity of
tissue distribution of the derivatives and species differences are discussed.
PMID- 9643439
TI - The effect of a drug-delivery system consisting of soybean phosphatidyl choline
and medium-chain monoacylglycerol on the intestinal permeability of hexarelin in
the rat.
AB - The aim of this study was to investigate if the effective in-situ permeability
(Peff) of a new growth hormone-releasing peptide, hexarelin, along rat intestine
was enhanced by a lipid matrix drug-delivery system comprising a mixture of
soybean phosphatidyl choline and medium-chain monoacylglycerol (PC-MG). The study
was performed with and without a protease inhibitor, Pefabloc SC. To enable
better understanding of the mechanism of action of this delivery system we also
studied the uptake of a small hydrophilic molecule, atenolol. PC-MG at a
concentration of 15 mmol L(-1) increased the jejunal Peff of hexarelin
approximately 20-fold, both in the presence and absence of Pefabloc SC, whereas
Peff was not increased in the ileum and colon. PC-MG had no effect on the
jejunal, ileal and colonic Peff of atenolol. Complete recovery of the non
absorbable molecule PEG 4000 showed that functional intestinal viability was
maintained in all experiments. Although the results obtained in this study are
promising, pharmacokinetic and toxicological studies are required to investigate
if this delivery system is a suitable and safe candidate for improving the oral
bioavailability of hexarelin.
PMID- 9643440
TI - Novel 5,8-diazabenzo[c]phenanthrenes: synthesis and mutagenicity.
AB - The polycyclic aromatic hydrocarbons have been recognized as carcinogens and
mutagens since the early part of this century. More recently their aza and
polyaza derivatives have been shown to have the same biological activity. A major
source of these compounds is the combustion of fresh or metamorphosed plant
materials; this contributes to the environmental burden of, and exposure to,
these carcinogens. We report the synthesis and characterization of a series of
novel 5,8-diazabenzo[c]phenanthrenes which are isosteric with the known epidermal
carcinogen benzo[c]phenanthrene but have not yet been reported as components of
soot or diesel particulate matter. The synthesis of the compounds exploits a
versatile, double Friedlander reaction between the appropriately substituted 2,2'
diaminobenzophenone and beta-diketones, with yields of purified product ranging
from 30-90%. The nucleophilic substitution of these diazabenzophenanthrenes with
ethanolamine is also described. This strategy will enable further elaboration of
these heterocyclic nuclei at a later date. Mutagenicity testing of these agents
was performed using spot tests and in Ames plate-incorporation assays using
Escherichia coli WP2 and WP2uvrA as test organisms. The plate-incorporation
assays were performed in the presence or absence of metabolic enzymes contained
in the S9 liver fraction from Aroclor 1254-induced rats, to investigate whether
bioactivation of the diazabenzophenanthrenes contributed to their toxicity. No
differences between these two protocols were observed, with neither test showing
reversion to prototrophic behaviour. Furthermore, the compounds were not toxic to
the test organism. These initial results suggest that these compounds are not
mutagenic in the Ames tests employed.
PMID- 9643441
TI - Novel aryl-bis-quinolines with antimalarial activity in-vivo.
AB - Three rationally designed isomeric aryl-bridged bis-quinolines, N1,Nx-bis(7
chloroquinolin-4-yl)phenylene-1,x-diamines, where x=2, 3 or 4, i.e. o-, m- and p
substituted analogues respectively, were synthesized and evaluated against
Plasmodium berghei in-vivo. The compound with x=2 had an ID50 of 30 mg kg(-1),
whereas the p-substituted analogue (x=4) was not statistically schizonticidal at
either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg
kg(-1), ID50=60 mg kg(-1) approx.). When the delivery vehicle was changed to
saline-DMSO, antimalarial potency increased for the p-substituted compound (ID50
17 mg kg(-1)). In contrast, the m-substituted analogue had marked antimalarial
activity (ID50 1.2 mg kg(-1)), which compares favourably with that of chloroquine
diphosphate (ID50 = 4.3 mg kg(-1)). The data presented show that the
aminomethylene side chain in amodiaquine can be successfully replaced by a 7-halo
4-aminoquinoline, establishing that carbon bridges containing less than four
contiguous carbon atoms can be present within highly active aryl-substituted 4
aminoquinoline antimalarials. These results confirm that the presence of an OH
group in the aryl bridge is not necessary for antimalarial activity and
substantiate the view that, despite the appearance of resistant strains, new and
existing aminoquinolines still have an important role in treating malaria.
PMID- 9643442
TI - Interspecies scaling: predicting volumes, mean residence time and elimination
half-life. Some suggestions.
AB - Extrapolation of animal data to assess pharmacokinetic parameters in man is an
important tool in drug development. Clearance, volume of distribution and
elimination half-life are the three most frequently extrapolated pharmacokinetic
parameters. Extensive work has been done to improve the predictive performance of
allometric scaling for clearance. In general there is good correlation between
body weight and volume, hence volume in man can be predicted with reasonable
accuracy from animal data. Besides the volume of distribution in the central
compartment (Vc), two other volume terms, the volume of distribution by area
(Vbeta) and the volume of distribution at steady state (VdSS), are also
extrapolated from animals to man. This report compares the predictive performance
of allometric scaling for Vc, Vbeta and VdSS in man from animal data. The
relationship between elimination half-life (t(1/2)) and body weight across
species results in poor correlation, most probably because of the hybrid nature
of this parameter. To predict half-life in man from animal data, an indirect
method (CL=VK, where CL=clearance, V is volume and K is elimination rate
constant) has been proposed. This report proposes another indirect method which
uses the mean residence time (MRT). After establishing that MRT can be predicted
across species, it was used to predict half-life using the equation MRT=1.44 x
t(1/2). The results of the study indicate that Vc is predicted more accurately
than Vbeta and VdSS in man. It should be emphasized that for first-time dosing in
man, Vc is a more important pharmacokinetic parameter than Vbeta or VdSS.
Furthermore, MRT can be predicted reasonably well for man and can be used for
prediction of half-life.
PMID- 9643443
TI - Effect of cyclosporin on liver antioxidants and the protective role of vitamin E
in hyperoxaluria in rats.
AB - This study aimed to evaluate whether administration of cyclosporin to
hyperoxaluric rats affects liver antioxidant status, and whether pretreatment
with vitamin E reverses the effect. Male Wistar rats were divided into two major
groups of 40. One group was given vitamin E. Both major groups were then divided
into four subgroups which received vehicle (olive oil), cyclosporin in olive oil
(50 mg kg(-1)), 3% ammonium oxalate or cyclosporin + 3% ammonium oxalate for
three days. The activities of liver lactate dehydrogenase, glycolic acid oxidase
and xanthine oxidase, and the level of malondialdehyde, an indicator of lipid
peroxidation, increased when cyclosporin was administered to hyperoxaluric rats.
The levels of antioxidants ascorbic acid, vitamin E and reduced glutathione and
the activities of glutathione-metabolizing enzymes were altered significantly
when hyperoxaluric rats were treated with cyclosporin. All these enzymes and
antioxidants showed highly significant correlation values, r. These changes were
restored to near normal by pretreatment with vitamin E. These findings suggest
that cyclosporin-induced hepatotoxicity is aggravated in hyperoxaluria. This was
almost totally prevented by pretreatment with vitamin E.
PMID- 9643444
TI - Investigation into the presence of insulin-degrading enzyme in cultured type II
alveolar cells and the effects of enzyme inhibitors on pulmonary bioavailability
of insulin in rats.
AB - The purpose of this study was to investigate the role of insulin-degrading enzyme
(IDE, EC 3.4.22.11) in insulin degradation in alveolar epithelium. The primary
culture of isolated rat type-II pneumocytes was used for the in-vitro
characterization of IDE. Insulin was then administered intratracheally with
various inhibitors to assess the improvement in its pulmonary bioavailability. In
cultured type-II pneumocytes, the cytosolic insulin-degrading activity
contributed 81% of total insulin degradation, reached a maximum at pH 7.5 and had
an apparent Michaelis-Menten constant (Km) of 135 nM. N-Ethylmaleimide, p
chloromercuribenzoic acid and 1,10-phenanthroline inhibited insulin-degrading
activity almost completely in both crude homogenate and cytosol. An
immunoprecipitation study showed that IDE contributed 74% of cytosolic insulin
degrading activity. Western blot analysis showing a single band of 110 kDa on
reduced SDS (sodium dodecylsulphate) gels confirmed the presence of IDE in
cultured type-II cells. When given intratracheally with insulin, inhibitors
including N-ethylmaleimide, p-chloromercuribenzoic acid, and 1,10-phenanthroline
significantly enhanced the absolute bioavailability of insulin and the compound's
hypoglycaemic effects. These results suggest that IDE is present in alveolar
epithelium and might be involved in limiting insulin absorption in the lung.
PMID- 9643445
TI - Metabolism of roxithromycin in the isolated perfused rat liver.
AB - Roxithromycin is a macrolide antibiotic with high clinical potency. N
Demethylation is considered to be one of the main pathways of roxithromycin
metabolism in rats. We have studied the hepatic metabolism of roxithromycin in
the isolated perfused rat liver. After addition of roxithromycin (30 microM) to
the perfusion medium the parent compound and one major metabolite were detected
in bile by high-performance liquid chromatography. The metabolite was identified
as monodesmethylated roxithromycin by mass spectrometric analysis. Onset of
biliary excretion of native roxithromycin was fast, reaching a maximum (130.52 +/
43.88 pmol g(-1) min(-1)) after only 10 min, whereas excretion of the metabolite
was delayed (maximum 75.83 +/- 11.92 pmol g(-1) min(-1) at 30 min). The
cumulative excretion of roxithromycin and its metabolite into bile during the 60
min of application amounted to only 1.09 +/- 0.30 and 0.64 +/- 0.22% of the
roxithromycin cleared from the perfusate during the same time. The liver content
was 0.48 micromol (g liver)(-1), indicating high retention within the organ. No
release of the metabolite into the perfusate was detected. In conclusion, this
study has demonstrated the importance of phase-I metabolism for the biliary
excretion of roxithromycin in rat liver. These findings might be predictive of
roxithromycin biotransformation and biliary excretion in man.
PMID- 9643446
TI - Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2
thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric
microsomes and in rats.
AB - We have investigated the properties of the newly synthesized proton-pump
inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on
gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and
gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+
ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its
classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6
on the proton pump was approximately 14-times higher than that of omeprazole at
pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on
gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less
active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently
protected the gastric mucosa from damage induced by water-immersion stress,
indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by
mepirizole. Repeated administration of YJA20379-6 also dose-dependently
accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These
results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects
which are exerted by suppression of H+/K+-ATPase activity in gastric parietal
cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer
diseases.
PMID- 9643447
TI - Effects of 17beta-oestradiol on rat isolated coronary and mesenteric artery tone:
involvement of nitric oxide.
AB - Pre- and post-menopausal women receiving oestrogen replacement therapy have a
significantly reduced risk of cardiovascular disorders. It has been suggested
that this protection might be partly a result of a direct relaxant effect of
oestrogens on coronary arteries. This study examines and directly compares the
effects of 17beta-oestradiol on rat isolated coronary and mesenteric vessels. The
influence of nitric oxide on these responses was also investigated. 17Beta
oestradiol caused similar concentration-dependent relaxation of isolated coronary
and mesenteric resistance arteries pre-contracted with either KCl (60 mM) or 9,11
dideoxy-11alpha,9alpha-epoxymethanoprostaglandin (U46619; 1 microM). The
relaxation responses to 17beta-oestradiol were significantly reduced, but not
totally inhibited, in the presence of N(omega)-nitro-L-arginine methyl ester (L
NAME), an inhibitor of nitric oxide synthase; they were not altered by
indomethacin, an inhibitor of prostaglandin synthesis. The responses to 17beta
oestradiol in the presence of L-NAME were not dependent on the vessel studied or
the pre-contracting agent used. These results suggest that nitric oxide might
contribute to the vasodilatory effects of 17beta-oestradiol in rat isolated
coronary and mesenteric resistance arteries.
PMID- 9643448
TI - 5-Hydroxytryptamine-induced secretion by rat jejunum in-vitro involves several 5
hydroxytryptamine receptor subtypes.
AB - The receptors contributing to 5-hydroxytryptamine (5-HT)-induced anion secretion
by rat jejunum have been investigated by testing the effects of selective
agonists and antagonists in-vitro using both intact and stripped intestinal
sheets. In both intact and stripped jejunum 5-HT and 5-methoxytryptamine, an
agonist that lacks affinity for 5-HT3 receptors, induced concentration-dependent
increases in the short-circuit current (SCC), although 5-methoxytryptamine
induced a smaller maximum response. In intact sheets 1-phenylbiguanide, a
selective 5-HT3 agonist, induced a response that was similar in magnitude to that
of 5-methoxytryptamine, but in stripped preparations it had little effect.
Tetrodotoxin inhibited the response of intact jejunum to 5-HT (by 86%) and 5
methoxytryptamine (by 85%) and abolished the response to 1-phenylbiguanide. In
stripped sheets inhibition of the 5-HT response by tetrodotoxin was reduced to
27%. Desensitization to 1-phenylbiguanide reduced the response to 5-HT in intact
but not stripped sheets whereas, in contrast, desensitization to 5
methoxytryptamine inhibited the 5-HT response in stripped sheets but was without
effect in intact sheets. Mianserin, a 5-HT1, 5-HT2 and 5-HT3 antagonist, and
renzapride, a 5-HT1 and 5-HT3 antagonist, both reduced the maximum response to 5
HT, but 5-HTP-DP, a 5-HT1 antagonist, was without effect. The 5-HT3 antagonist
granisetron reduced the response to 5-HT in intact, but not in stripped sheets.
Tropisetron, a 5-HT3 and 5-HT4 antagonist, inhibited the response to 5
methoxytryptamine in both preparations, but did not alter the response to 5-HT.
It is concluded that 5-HT-induced jejunal secretion involves more than one 5-HT
receptor subtype, with both neural and non-neural mechanisms contributing to the
response.
PMID- 9643449
TI - Effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic
ulceration in the guinea-pig.
AB - D-002 is a natural mixture of higher aliphatic primary alcohols, isolated and
purified from beeswax which has anti-inflammatory properties, reduces
leukotrienes (LTB4) and thromboxane B2 (TXB2) in exudated carrageenan-induced
pleurisy, and has anti-ulcer activity in different experimental models. This
study was conducted to determine the effect of D-002 on the pre-ulcerative phase
of carrageenan-induced colonic ulceration in guinea-pigs. Animals were randomly
distributed among a negative control, a positive control group treated with the
vehicle Tween 20 in H2O and two experimental groups receiving D-002 at 25 and 50
mg kg(-1). All treated animals received degraded carrageenan for three days for
induction of colonic ulceration. Significant reductions in wet weight, wall
thickness, counts of infiltrating polymorphonuclear neutrophils and of
macrophages, and histological index were observed in colonic mucosa of D-002
treated animals compared with controls. It is concluded that D-002 has a
protective effect on the pre-ulcerative phase of carrageenan-induced colonic
ulceration in the guinea-pig.
PMID- 9643450
TI - Effects of the ginsenosides Rg1 and Rb1 on morphine-induced hyperactivity and
reinforcement in mice.
AB - Recent studies have demonstrated that ginseng saponin inhibits the hyperactivity
and conditioned place-preference response induced by psychostimulants and
opiates. This seems to occur by direct or indirect modulation of dopaminergic
activity. However, it is not known which components of ginseng saponin are
active. These experiments were conducted to determine the effects of the
ginsenosides Rb1 and Rg1, major components of the protopanaxadiol and
protopanaxatriol fractions of ginseng saponin, on morphine-induced hyperactivity
and conditioned place-preference. Morphine-induced hyperactivity, but not
apomorphine-induced climbing behaviour, was inhibited by both Rb1 and Rg1. These
findings confirm the hypothesis that ginsenosides modulate catecholaminergic
activity preferentially at pre-synaptic sites. Morphine-induced conditioned place
preference was inhibited by Rg1, but not by Rb1. It has previously been shown
that at low doses Rb1 and Rg1 are equally effective at inhibition of
catecholamine secretion at the pre-synaptic site, but that at high doses Rg1 is a
more effective inhibitor. This observation might explain our finding that
morphine-induced conditioned place-preference was inhibited by Rg1 only. Our
findings suggest that Rg1, a component of ginseng saponin with appropriate
activity, might be a useful agent for prevention and treatment of the adverse
effects of morphine.
PMID- 9643451
TI - Flavonoids reduce morphine withdrawal in-vitro.
AB - The effects of quercetin, flavone, catechin and chrysin on the naloxone
precipitated withdrawal contracture of the acute morphine-dependent guinea-pig
ileum have been investigated in-vitro. After 4 min in-vitro exposure to morphine
a strong contracture of guinea-pig isolated ileum was observed after the addition
of naloxone. All the flavonoids, injected 10 min before morphine at
concentrations between 10(-7) and 10(-5) M, were capable of blocking naloxone
induced contracture after exposure to morphine in a concentration-dependent
fashion. IC50 values calculated for quercetin, flavone, catechin and chrysin were
2.7 x 10(-6), 7.3 x 10(-7), 8.5 x 10(-7) and 5.3 x 10(-6) M, respectively. These
results suggest that flavonoids might play an important role in the control of
morphine withdrawal.
PMID- 9643452
TI - Plasma salicylate levels in surgical patients during the postoperative period.
PMID- 9643453
TI - Analysis of the phenotype and phagocytic activity of monocytes/macrophages from
cattle infected with the bovine leukaemia virus.
AB - The bovine leukaemia virus (BLV) is a retrovirus that infects mainly B
lymphocytes of cattle, but proviral DNA can also be isolated from
monocytes/macrophages. This study investigated the effect of BLV infection on
surface antigens on freshly isolated peripheral blood monocytes and cultured
monocyte-derived macrophages, with and without lipopolysaccharide (LPS)
stimulation. The effect of BLV infection on phagocytic activity of CD14+
monocytes was also assessed. The percentage of monocytes expressing the surface
antigens CD11b, CD32 (FcgammaRII), MHC class II and the surface antigen
recognised by mAb DH59B were increased in BLV-positive cattle. In contrast,
expression intensity of all markers was low in samples from BLV-positive cattle.
CD14+ monocytes from BLV-positive cattle showed less Fcgamma-receptor-mediated
phagocytosis compared to monocytes from BLV-negative cattle. After 7 days in
culture, there was evidence for shedding/downregulation of surface antigens on
monocyte-derived macrophages, in particular on cells from BLV-positive cattle.
LPS stimulation decreased the percentage of cells expressing the measured markers
in monocyte-derived macrophages taken from BLV-negative cattle, but not in
cultures derived from BLV-positive cattle. The results provide further evidence
for an altered function of monocytes and macrophages in BLV-infected cattle.
PMID- 9643454
TI - Enzymatic amplification and expression of bovine interleukin-1 receptor
antagonist cDNA.
AB - cDNA generated from lipopolysaccharide-stimulated bovine peripheral blood
mononuclear cells was used to amplify and clone the bovine interleukin-1 receptor
antagonist (IL-1ra) using primers derived from semi-conserved regions between
human and mouse IL-1ra sequences. 5' and 3' terminal sequences of bovine IL-1ra
were amplified by 5' and 3' rapid amplification of cDNA ends. The deduced amino
acid sequence of bovine IL-1ra demonstrated 80%, 78%, 78%, 77% and 76% homology
with human, mouse, rat, rabbit and equine sequences, respectively. Recombinant
bovine IL-1ra produced in Escherichia coli suppressed the growth inhibitory
activity of bovine IL-1beta on A375 cells in a dose-dependent manner, indicating
that the present bovine IL-1ra cDNA encodes biologically active proteins.
PMID- 9643455
TI - Characterization of differentially expressed genes in the bovine T lymphoma cell
line.
AB - A differential display (D.D.) analysis was made to detect differentially
expressed genes in a bovine T lymphoma cell line, BTL-26, derived from the calf
type of sporadic bovine lymphosarcoma. A D.D. analysis comparing BTL-26 with the
bovine epithelial cell line CKT-1 and healthy bovine thymocytes yielded 24 cDNA
clones. The DNA sequencing analysis followed by a homology search showed that 20
of the 24 cDNA clones had no significant homology to any sequences in DNA data
base. The remaining four genes were homologous to known sequences. Northern blot
hybridization among BTL-26, CKT-1 and healthy bovine thymocytes showed that a
cDNA clone, BC8, was differentially expressed in BTL-26. The cloning of full
length cDNA for the BC8 clone and its DNA sequences showed that the BC8 clone is
a bovine nuclear domain protein homologous to the human NDP52 gene. Northern blot
analysis showed that the BC8 clone bovine NDP52 was predominantly expressed in
tumor cell line BTL-26, compared with the transcripts from several bovine
tissues.
PMID- 9643456
TI - The effects of virus-specific antibodies on the replication of bovine respiratory
syncytial virus in vitro and on clinical disease and immune responses in lambs.
AB - Low concentrations of antibodies, specific to human respiratory syncytial virus
(RSV) have been shown to enhance virus replication in human monocytic cell lines
by several workers. In the present study, replication of bovine RSV in ovine
peripheral blood monocytes was shown to be enhanced in the presence of low
concentration of bovine RSV-specific antibodies. Antibodies had no enhancing
effect on virus replication in secondary lamb testis cells or monocytic cell
lines derived from peripheral blood monocytes. The possible effects of low titres
of bovine RSV-specific antibodies on the development of clinical disease were
examined by inoculating groups of lambs with a mixture of virus and antibodies
and assessing the severity of clinical disease and by measuring venous oxygen
(PO2) and carbon dioxide (PCO2) tensions, as hypoxia has been associated with
respiratory diseases. Inoculation of bovine RSV and virus-specific antibody
complexes to lambs did not enhance clinical disease and had no effect on the
clinical chemistry, haematology and PO2 and PCO2 tensions. Groups of lambs
inoculated with virus alone or virus-antibody complexes developed significant
humoral and cellular immune responses. There was no significant difference in the
cellular immune responses of lambs exposed to virus alone and lambs exposed to
virus-antibody mixture, as measured by virus-specific lymphocyte transformation
or by cytotoxicity assays but the period of virus shedding was longer in lambs
inoculated with a mixture of virus and immune serum.
PMID- 9643457
TI - Flow cytometric measurement of neutrophil alkaline phosphatase before and during
initiation of an induced Escherichia coli mastitis in cattle.
AB - In 12 healthy cows, neutrophil alkaline phosphatase (NAP) activity was measured
by flow cytometer before and during an experimentally induced Escherichia coli
mastitis, to study the role and increase of NAP in Gram-negative bacterial
infections. Percentage of neutrophils containing alkaline phosphatase and
intensity of NAP activity were measured. Preinfection percentage of neutrophils
with enzyme activity varied between 64.0% and 84.4% and the intensity of enzyme
activity was low in all cows. After induction of infection, percentage of
neutrophils with enzyme activity showed a significant decrease on day 1 followed
by an significant increase on day 3. NAP intensity increased significantly on the
second and third day after infection. This increase of intensity was
significantly, positively correlated with the severity of infection. From this
study we may conclude that variation in susceptibility to E. coli mastitis could
not be explained by preinfection NAP levels. The post-infection increase of NAP
activity, that was found following an induced infection was more a result of
increased enzyme intensity per neutrophil, then from an increase of percentage
neutrophils with enzyme activity. Furthermore, a strong correlation was found
between NAP intensity and severity of inflammation. There was evidence that the
more severely diseased animals showed stronger NAP intensity increase.
PMID- 9643458
TI - Zinc, thymic endocrine activity and mitogen responsiveness (PHA) in piglets
exposed to maternal aflatoxicosis B1 and G1.
AB - Growth retardation, thymic involution and impaired peripheral immune efficiency
are constant events in piglets exposed to maternal aflatoxicosis. Zinc may play a
key role because of its requirement for good immune responses, including thymic
endocrine activity. Zinc is required to activate a thymic hormone, i.e. thymulin
(ZnFTS), which is responsible for cell-mediated immunity. Zinc deficiency and
decreased thymic endocrine activity are present in piglets fed from sows exposed
to aflatoxins (AF) B1 and G1 as compared with healthy control piglets. In
particular, active ZnFTS is decreased while concentrations of inactive thymulin
(FTS) are high. The in vitro addition of zinc up to the plasma samples induces a
reduction of inactive thymulin. The lymphocytes mitogen responsiveness (PHA) is
decreased and a thymic cortical lymphocyte depletion is also present. These data
suggest that the thymic defect, followed by impaired peripheral immune
efficiency, may largely depend by the low peripheral zinc bioavailability to
saturate all thymulin molecules produced.
PMID- 9643459
TI - Induction of a local and systemic immune response using cholera toxin as vehicle
to deliver antigen in the lamina propria of the chicken intestine.
AB - In this study, the humoral mucosal immune response to a recombinant Eimeria
antigen (Ea1A) was enhanced using cholera toxin (CT). Chickens were primed intra
intestinally with Ea1A either conjugated or not to CT. The local and systemic
antibody responses to both Ea1A and CT were determined to find out whether the
chickens could respond to CT and whether both antigens had reached the lamina
propria. In addition the effects of CT on lamina propria leukocytes were
examined. The results showed that chickens had receptors on the caecal epithelium
that could bind CT. At day 7 after administration, the number of CD4+ and CD8+ T
lymphocytes in the lamina propria of the caecum had increased, indicating that CT
had a specific immunological effect. At this timepoint, anti-CT antibody
containing cells were detected locally in the lamina propria of the caecum. In
serum all antigen preparations containing CT induced IgM and IgG antibody titres
specific for CT within 10 days after priming. In addition, the recombinant Ea1A
antigen also induced serum responses when administered together with CT or
conjugated to CT, thus both CT and the antigen had reached the lamina propria.
Nevertheless, the Ea1A specific response was much higher in the primary response
and after booster immunization when the antigen was conjugated to CT than when
only mixed with CT. Therefore, we conclude that CT is a suitable adjuvant for
intra-intestinal application in chickens, especially when the antigen is
conjugated to it.
PMID- 9643460
TI - Expression of surface antigens on blood and mammary leukocytes in lactating and
dry ewes.
AB - Flow cytometry was used to study the expression of CD4, CD8, CD14, CD18, WC1,
MHCII, B-cell and L-selectin on CD45+ leukocytes in ovine blood and mammary
secretions from lactating and dry ewes. The proportion of CD4+ lymphocytes was
significantly lower and the proportion of CD8+ lymphocytes significantly higher
in mammary secretions than in blood. This suggests that a selective migration to
or retention of CD8+ cells in favour of CD4+ cells occurs in the mammary gland. L
selectin staining intensity on lymphocytes and neutrophils was lower in mammary
secretions than in blood. In contrast, CD18 staining intensity was higher on
leukocytes in milk, but not in dry secretions, than on corresponding cells in
blood. These changes in adhesion molecules are in accord with shedding of L
selectin and up-regulation of CD18 during transendothelial migration. Expression
of leukocyte antigens differed with lactational status mainly in mammary
secretions. In milk, the staining intensity of CD18+ lymphocytes and neutrophils
was higher than in dry secretions and more milk neutrophils expressed L-selectin.
In contrast, greater numbers of IL-2R+ and MHCII+ lymphocytes and CD14+
leukocytes were observed in dry secretions. An increased proportion of these
subpopulations could lead to increased immunological responsiveness of the udder
during the dry period.
PMID- 9643461
TI - HIV, AIDS, and other health risks: findings from a multisite study--an
introduction.
AB - In late 1990 the National Institute on Drug Abuse (NIDA) initiated the
Cooperative Agreement (CA) for AIDS Community-Based Outreach/Intervention
Research Program. The goal of this program was to prevent the further spread of
HIV among out-of-treatment drug users, in particular injection drug users (IDUs)
and crack cocaine users, their sexual partners, and those at risk for initiating
injection behavior. To accomplish this goal, the CA set out to monitor drug use
and HIV risk behaviors, assess the efficacy of various HIV risk reduction
interventions, and develop and refine outreach and intervention strategies.
Twenty-three research sites, 21 rural and urban sites in the United States and
one each in Puerto Rico and Brazil, were included in the CA program. This article
presents an overview of the CA as well as a synopsis of the studies covered in
this special issue examining the total CA database.
PMID- 9643462
TI - A cluster analysis of not-in-treatment drug users at risk for HIV infection.
AB - The purpose of the analysis described here was to classify not-in-treatment drug
users participating in the National Institute on Drug Abuse (NIDA)-sponsored
Cooperative Agreement study into several "homogeneous" HIV risk groups using
cluster analysis. Data for this analysis (N=17,778) were collected at 19 study
sites in the United States and Puerto Rico. Measures selected for the cluster
analysis were limited to (a) current drug use and HIV risk behaviors, (b)
mutually exclusive behaviors, (c) behaviors directly related to HIV risk, and (d)
behaviors that were not statistically rare. Eight homogeneous HIV risk clusters
were produced. Crack cocaine use was the most distinguishing feature of three
clusters. Another three clusters were distinguishable by drug injection and
needle use practices. Two additional clusters could not be grouped with either
the crack- or the injection-dominant clusters. Prostitution was the most
distinguishing risk behavior of one of these clusters, and extremely high drug
injection frequencies and relative rates of risky needle use characterized the
other. Composition of the clusters varied significantly by gender,
race/ethnicity, educational attainment, and drug use characteristics. In
addition, perceptions and behaviors initiated to reduce the chances of becoming
infected with HIV varied by cluster. Subjects in the crack-predominant clusters
reported low perceptions of the chances of getting AIDS. Perceptions of the
chances of becoming infected with HIV among subjects in the injection-predominant
clusters were strongly related to injection frequency. Seroprevalence was also
related to cluster. Higher rates of HIV infection were evident among the
injection-predominant clusters, and higher rates were related to frequency of
injection and the rate of risky needle use. Among the crack-predominant clusters,
the relationship between drug use and sexual behaviors and HIV infection was less
clear.
PMID- 9643463
TI - Needle transfer among injection drug users: a multilevel analysis.
AB - OBJECTIVE: The purpose of the study described here is to extend our understanding
of needle transfer behaviors among injection drug users (IDUs) by combining both
micro and macro variables in a multilevel model. METHODS: A sample of 8,404 IDUs
interviewed at 18 sites of the National Institute on Drug Abuse (NIDA)
Cooperative Agreement for AIDS Community-Based Outreach/Intervention Program
(COOP) was used for the study. A multilevel model was employed to deal with
intraclass correlation in the sample and to evaluate the impact of micro and
macro variables on needle transfer among IDUs. RESULTS: A significant intraclass
correlation was detected in the sample. Needle transfer was associated with both
the individual characteristics and the features of the social setting in which
they were embedded. Some of the micro slopes were fixed, while some varied from
site to site, depending on the values of macro variables. The micro intercept and
the micro slope of ethnicity vary randomly across social settings, while they are
partially determined by macro variables. CONCLUSION: Considering the intraclass
correlation in the data and the effects of contextual features on individual
behaviors, multilevel analysis of HIV risk behaviors should be considered when
combining data from micro and macro levels (e.g., individual and project site
levels).
PMID- 9643464
TI - Cluster analysis of HIV intervention outcomes among substance-abusing women.
AB - The study described here presents an innovative approach to analyzing
intervention outcomes among women substance abusers participating in a national
HIV prevention research study funded by the National Institute on Drug Abuse. We
used cluster analysis to divide the women in our sample (N=557) into four
distinct subgroups predominantly characterized by differences in drug use,
injecting risk, sexual behaviors, and drug and sexual risk combined. The four
subgroups resulting from this process were primary crack-using women, primary
needle-using women, high-frequency needle-using women, and women with multiple
drug and sex risk behaviors. Our analysis focuses on changes in self-reported
risk behaviors from baseline to 6-month follow-up. In general, the results
clearly indicate that the women are heterogeneous; that is, the subgroups exhibit
varying patterns of drug use, injecting risk, sexual behavior, and HIV
seropositivity. Significant outcomes were found in many areas, indicating
positive changes in risk behaviors. The two smaller subgroups of women--high
frequency needle users and those in the multiple-risk behavior subgroup--reported
the highest rate of high-risk behaviors and seropositivity but also showed the
greatest change at follow-up. A particularly important finding resulting from our
analytical approach is that well over half the women in our sample were primary
crack users (n=313). This finding is even more significant in light of the fact
that the Cooperative Agreement specifically tried to include 70% or more
participants who were injectors. Although the rate of HIV seropositivity is not
as high for this crack-using subgroup as for the two smaller needle-using
subgroups, a greater number of "women who are HIV positive" are in this primary
crack-using subgroup than in all the other subgroups. Most of the crack-using
women reported that they were not currently injecting drugs and never shared
needles, but 10% were seropositive for HIV, suggesting that their risk comes
primarily from sexual behaviors. Behaviors in this larger subgroup of women did
not change as dramatically as those of women in the smaller subgroups; however,
the women did show improvement in areas related to indirect risk (e.g., alcohol
and crack use) and in several areas where change is most needed (e.g., trading
sex for drugs and using condoms). The results demonstrate a promising alternative
approach to analyzing substance abuse and HIV risk behaviors, and they suggest
the need for further research on alternative interventions for women with
different patterns of risk behaviors.
PMID- 9643465
TI - The effect of entering drug treatment on involvement in HIV-related risk
behaviors.
AB - The research described here is based on a sample of 8,241 out-of-drug-treatment
users of injected drugs and/or crack, aged 18 or older, recruited from 22 sites
across the United States and Puerto Rico. The study divided respondents into
three groups-(a) cocaine or crack users who did not also use heroin or speedball
(cocaine-only users), (b) heroin injectors who did not also use cocaine or crack
or speedball (heroin injectors), and (c) users of cocaine or crack and injected
heroin or speedball (dual users)--and compared the efficacy of entering drug
treatment for these groups' involvement in HIV-related risk behaviors. The study
found that entry into treatment corresponded to greater reductions in substance
abusers' frequency of drug use and involvement in risky injection practices
compared to those observed in people who did not enter treatment between their
baseline and 6-month follow-up interviews. Entry into drug treatment was also
associated with reductions in the practice of risky sexual behaviors, but these
reductions were less substantial and less consistent than those noted for drug
use and injection risk behaviors.
PMID- 9643466
TI - Gonorrhea among drug users: an Alaskan versus a national sample.
AB - The study described here investigates the replicability of gender-specific risk
profiles for gonorrhea based on an Alaskan sample compared to a U.S. national
sample of drug users at risk for HIV infection. The Alaska sample (interviewed at
a field station in Anchorage, Alaska; N=1,049) and the national sample
(interviewed at 18 sites other than Alaska; N=17,619) consisted of cocaine
smokers and injection drug users not in drug treatment. A history of gonorrhea
infection was self-reported and coded as ever or never. The Anchorage and
national risk profile for men included the following factors: (a) history of
intranasal or parenteral cocaine use, (b) being black versus nonblack, (c) being
older, (d) income from illegal activity, and (e) history of amphetamine use. The
Anchorage and national risk profiles for women included the following factors:
(a) trading sex for money, (b) being Native American versus non-Native American,
and (c) trading sex for drugs. The Anchorage model for women included perceived
homelessness as a factor, but it was not retained in the national model. The
extent of the replicability of these models illustrates the generalizability of
Alaskan findings to other U.S. drug-using populations. The authors also discuss
the implications of these findings for disease prevention.
PMID- 9643467
TI - Prevalence of HIV infection and HIV risk behaviors associated with living place:
on-the-street homeless drug users as a special target population for public
health intervention.
AB - The study described here examined the prevalence of HIV infection as a function
of place of residence and high-risk behaviors in six subpopulations of out-of
treatment drug injectors and crack cocaine users who participated in the National
Institute on Drug Abuse (NIDA) Cooperative Agreement project. The subpopulations
were blacks, Hispanics, and non-Hispanic whites sampled separately by gender. The
research asked three questions: (a) Is the HIV infection rate higher among the on
the-street homeless than among those in other places of residence? (b) Do high
risk drug-related behaviors differ by housing status? and (c) What are the joint
effects of high-risk drug-related behaviors and housing status on the probability
of HIV infection? Overall, on-the-street homeless had a significantly higher HIV+
rate (19.0%) than the study population as a whole (11.2%). Rates differed by
gender and race, with exceptionally high HIV+ rates for on-the-street homeless
Hispanic males (29%) and females (32%) and for on-the-street homeless black
females (38%). Having used drug works previously used by a HIV-infected person
was a strong predictor of HIV+ status, as was frequency of drug injections and
crack use. Having multiple sex partners was also a significant risk behavior.
Findings argue against considering on-the-street homelessness as equivalent to
shelter dwelling or aggregated homelessness for purposes of the AIDS epidemic. On
the-street homeless drug users were at strong risk for acquisition and
transmission of HIV infection and therefore in need of targeted-racially
relevant, ethnically relevant, and gender-relevant-public health interventions to
help prevent the spread of AIDS.
PMID- 9643468
TI - Variation in drug injection frequency among out-of-treatment drug users in a
national sample.
AB - This article analyzes data on drug injection frequency in a sample of more than
13,000 out-of-treatment drug injectors interviewed across 21 U.S. cities and
Puerto Rico through the National Institute on Drug Abuse (NIDA) Cooperative
Agreement for AIDS Community-Based Outreach/Intervention Research Program. The
goals of the article are to present findings on injection frequency and to
predict variation in terms of a set of variables suggested by previous research,
including location, ethnicity, gender, age, educational attainment, years since
first use of alcohol and marijuana, income, living arrangement, homelessness,
drugs injected, and duration of injection across drugs. Three models were tested.
Significant intersite differences were identified in injection frequency,
although most of the other predictor variables we tested accounted for little of
the variance. Ethnicity and drugs injected, however, were found to be
significant. Taken together, location, ethnicity, and type of drug injected
provide a configuration that differentiated and (for the variables available for
the analysis) best predicted injection frequency. The public health implications
of these findings are presented.
PMID- 9643469
TI - ELISA for the detection of venom antigens in experimental and clinical envenoming
by Loxosceles intermedia spiders.
AB - Enzyme linked immunosorbent assays (ELISA) were developed to detect antigens from
Loxosceles intermedia spider venom. Hyperimmune horse anti-Loxosceles intermedia
IgGs were prepared by immunoaffinity chromatography and used to set up a sandwich
type ELISA. The specificity of the assay was demonstrated by its capacity to
correctly discriminate the circulating antigens in mice that were experimentally
inoculated with L. intermedia venom from those inoculated with L. gaucho, L.
laeta, and Phoneutria nigriventer spider venoms, Tityus serrulatus scorpion venom
and Bothrops jararaca, Crotalus durissus terrificus, Lachesis muta muta and
Micrurus frontalis snake venoms. Measurable absorbance signals were obtained with
0.8 ng of venom per assay. The ELISA also detected antigens in the sera of
patients envenomed by L. intermedia. Therefore, after standardization for
clinical use this ELISA may be a valuable tool for clinicians and
epidemiologists.
PMID- 9643470
TI - Recovery from the lethal effects of saxitoxin: a therapeutic window for 4
aminopyridine (4-AP).
AB - We have shown that saxitoxin (STX) induced lethality can be reversed by 4-AP when
it is administered at the time of respiratory arrest [Benton, B. J., Spriggs, D.
L., Capacio, B. R. and Chang, F.-C. T. (1995) 4-Aminopyridine antagonizes the
lethal effects of saxitoxin (STX) and tetrodotoxin (TTX). International Society
of Toxicology, 5th Pan American Symposium on Animal, Plant and Microbial Toxins,
Frederick, MD. July/August 1995, p. 217]. The purpose of this study was to
determine whether 4-AP's efficacy could be enhanced further when administered at
different times relative to STX intoxication. The animals used in this study were
chronically instrumented for concurrent recordings of diaphragm electromyogram
(DEMG), neck skeletal muscle electromyogram, Lead II electrocardiogram, and
electrocorticogram (ECoG). There were five groups of unanesthetized guinea pigs.
The first group served as 4-AP controls and received a 2 mg/kg i.m. dose of 4-AP.
The four remaining groups were given a lethal dose of STX (5 microg/kg i.m.); the
second group, STX controls, received no 4-AP; the third group, the 4-AP treatment
group, received 4-AP immediately following cardiorespiratory collapse; the fourth
group was the 4-AP/STX co-administration group and 4-AP was given concurrently
with STX; and the fifth group was the 4-AP pretreatment group in which 4-AP was
given 10 min before STX. At the point of STX-induced cardiorespiratory collapse,
the guinea pigs were ventilated and given an i.p. injection of sodium
bicarbonate. Results showed that 4-AP prevented cardiorespiratory collapse in 3/7
animals in the 4-AP pretreatment group. Also, 4-AP in conjunction with artificial
ventilation and sodium bicarbonate accelerated recovery from STX-induced
cardiorespiratory collapse in all the treatment groups compared to the STX
controls.
PMID- 9643471
TI - Purification and properties of phospholipases A2 from the crown-of-thorns
starfish (Acanthaster planci) venom.
AB - Two phospholipases A < inf2 (named AP-PLA2-I and II) were purified from the crown
of-thorns starfish (Acanthaster planci) venom. Both enzymes were confirmed to be
PLA2s, based on the results that they showed hemolytic activity only in the
presence of phosphatidylcholine (PC) and also released fluorescent fatty acids
from PC with labeled fatty acids at the sn-2 position. The enzyme activity of
both PLA2s was enhanced by Ca2+ but reduced by Cu2+ and Zn2+. The molecular mass
of AP-PLA2-I was estimated to be 28 kDa by gel filtration and 15 kDa by SDS-PAGE,
indicating that AP-PLA2-I is a dimer composed of the same subunit. In contrast,
AP-PLA2-II was judged to be a monomer with a molecular mass of 12 kDa (gel
filtration) or 15 kDa (SDS-PAGE). The amino acid compositions of the two enzymes
were comparable to each other; Asx, Glx and Gly were rich in both molecules,
while Met, His and Trp were poor. Analyses by a sequencer determined the first 62
amino acid residues for both PLA2s. In the AP-PLA2-I preparation, minor amino
acids were additionally found at 17 positions, suggesting the coexistence of
another PLA2-component. As compared to the N-terminal sequences of the known
PLA2s, both AP-PLA2-I and II were identified as class I enzymes not only because
they have Cys-11 and lack Cys-51 but also because they contain the elapid loop in
the region 53-61.
PMID- 9643472
TI - Purification of a 5-HT uptake inhibitor from the venom of Cerastes vipera.
AB - A protein that inhibits the re-uptake of 5-hydroxytryptamine into rat brain
synaptosomes was isolated from the venom of the Sahara sand viper (Cerastes
vipera) by gel filtration and reverse phase chromatography. It has a molecular
weight of 13,739 Da and an IC50 of about 50 nM for blocking uptake of 3H-5-HT
into rat brain synaptosomes. It also augmented the responses to 5-HT in a smooth
muscle preparation. It has phospholipase A2 activity, but it has no lytic
activity as measured by its inability to release lactate dehydrogenase from rat
brain synaptosomes. Determination of the N-terminal sequence revealed a
similarity with a phospholipase A2 previously isolated from Cerastes cerastes
venom.
PMID- 9643473
TI - Structures and biological activities of new wasp venom peptides isolated from the
black-bellied hornet (Vespa basalis) venom.
AB - The black-bellied hornet (Vespa basalis) is the most dangerous species of vespine
wasps found in Taiwan. The hornet possesses a highly toxic venom which is rich in
toxin, enzymes and biologically active peptides. Using ultrafiltration to remove
the high molecular weight toxin and enzymes followed by reverse-phase HPLC, three
bioactive tridecapeptides, designated "HP-1, HP-2 and HP-3" were isolated from
the venom. Their amino acid sequences were determined as: HP-1: LFRLIAKTLGSLM, HP
2: LFRLLANTLGKIL, HP-3: IFGLLAKTLGNLF. The primary structures of these peptides
appear to be homologous to those of chemotactic peptides isolated from other
vespid venoms. However, these peptides show little chemotactic activity on human
neutrophils and have distinct tripeptide sequences at the amino and carboxylic
terminal sides, as compared with other hornet chemotactic peptides. The lack of
Pro3 which is a characteristic structure of vespid chemotactic peptides in their
sequences is most distinctive. Circular dichroism spectra of these peptides
measured in 20% trifluoroethanol show a high content of alpha-helical
conformation. All three peptides provoked local edema in rat hind paw, which
could be inhibited by antihistamine (diphenhydramine) and drug with antiserotonin
activity (cyproheptadine). These peptides also exhibited a potent hemolytic
activity which was potentiated by a non-lytic dose of the hornet lethal protein,
suggesting a supporting role of these peptides in the lethal effect of Vespa
basalis venom.
PMID- 9643474
TI - Resistance of eels (Gymnothorax) to the venom of sea kraits (Laticauda
colubrina): a test of coevolution.
AB - Eels of the genus Gymnothorax from the Pacific are selectively preyed upon by
banded sea kraits (Laticauda colubrina) and have been reported to sustain massive
doses of sea krait venom without ill effect. By contrast, the present study found
that Gymnothorax moringa from the Caribbean, where no sea snakes occur, are
sensitive to sea krait venom, with doses as low as 0.01 mg dry wt of venom/kg wet
wt of eel resulting in signs of envenomation, and doses as small as 0.1 mg/kg
proving to be lethal. These observations suggest that the resistance of Pacific
Gymnothorax to sea krait venom results from coevolution of predator and prey,
rather than from a general hardiness of Gymnothorax. This theory is supported
further by literature reports of sensitivity to sea snake venom by other taxa of
non-coevolved eels that either are allopatric with sea snakes (Anguilla), or are
sympatric with them but occupy different habitats and are not preyed upon by them
(Heteroconger).
PMID- 9643475
TI - Occurrence of a methyl derivative of saxitoxin in Bangladeshi freshwater puffers.
AB - A new component of paralytic shellfish poison was isolated from a Bangladeshi
freshwater puffer Tetraodon cutcutia. Its structure was deduced to be carbamoyl-N
methylsaxitoxin based on electrospray ionization mass spectrometry, [1H] NMR, and
conversion experiments.
PMID- 9643476
TI - In vitro effects of smokeless tobacco extract on tumor necrosis factor-alpha (TNF
alpha) and interleukin-1beta (IL-1beta) production, and on lymphocyte
proliferation.
AB - The use of smokeless tobacco (moist snuff) products is associated with mucosal
lesions, gingival recession, attachment loss, and oral cancer. Despite numerous
reports on the general toxic effects of smokeless tobacco extract, little
information is available regarding the specific effects of smokeless tobacco on
immune response. Inflammatory cytokines released as a result of smokeless tobacco
induced irritation may play a role in the development of oral mucosal lesions at
habitual tobacco placement sites in smokeless tobacco users. Consequently, the
purpose of this study was to determine whether an aqueous extract of smokeless
tobacco (STE) affects the secretion of tumor necrosis factor-alpha (TNF-alpha),
interleukin-1beta (IL-1beta), and the proliferation of lymphocytes. A macrophage
cell line (J774-A1) was used to measure the effects of STE on tumor necrosis
factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) secretion. Mouse
splenocytes were used to assess the effects of STE on lymphocyte proliferation.
We found that STE at low concentrations enhanced the production of both TNF-alpha
and IL-1beta. Furthermore, STE at similar concentrations enhanced mitogen-induced
murine splenocyte proliferation. Overall, these data suggest that smokeless
tobacco upregulated two key proinflammatory cytokines and also induces lymphocyte
proliferation.
PMID- 9643477
TI - Isolation and characterization of an endogenous inhibitor of phospholipase A2
from Indian cobra (Naja naja naja) venom.
AB - A PLA2-inhibitor has been purified from Indian cobra (Naja naja naja) venom by
the combination of ion-exchange and gel-filtration chromatography. The inhibitor,
NN-I3 was a peptide with mol.wt 6500 and has a fluorescence emission maxima ca
340 nm. NN-I3 specifically inhibited the enzyme activity of the three acidic PLA2
from the same venom. The inhibition of NN-I2d-PLA2 and NN-I2c-PLA2 by NN-I3 was
of mixed type and NN-I2c-PLA2 was of uncompetitive type. Neither the inhibitor
nor the individual mixtures of acidic PLA2 with the inhibitor (1:1 w/w or 1:2
mol:mol) were lethal to mice when injected intraperitoneally in doses up to 10 mg
kg(-1) body weight.
PMID- 9643478
TI - Brain neurotoxicity of Penitrem A: electrophysiological, behavioral and
histopathological study.
AB - The neurotoxicity of Penitrem A (PA) in rats was assessed against
neurophysiological, behavioral and histopathological parameters. Animals were
acutely given intracerebroventricular (22-45 mg) or intraperitoneal injections
(0.5-1.5 mg/kg) of PA. A typical trembling syndrome associated with PA was always
noted. Depending on the dose administered, animals may convulse and eventually
die (1-1.5 mg/kg). PA-induced transient alterations of the EEG involving an
increase in the frequency and voltage of electrical activity recorded from the
cerebral cortex. Hippocampal activity was not modified and some pathologic
activities may be recorded at the thalamus. Generally these EEG alterations
disappeared at d 3 after the injection and the animals progressively recovered.
However in the most severe cases, neuromotor disturbances were maintained at d 7
(rotarod test). Coronal sections of the brain at the striatal, thalamic,
hippocampal and pons levels mainly revealed that PA was able to induce dose
related injuries in the cerebellum with massive degeneration of Purkinje cells
and a significant vacuolization within the molecular layer. The neurotoxic
mechanism remains unclear. Action of the mycotoxin on the cerebello-thalamo
cortical tract is discussed.
PMID- 9643479
TI - Effect of oral supplementation of vitamin E on the hemolysis and erythrocyte
phospholipid-splitting action of cobra and viper venoms.
AB - In the present investigation, it was found that oral supplementation of graded
amounts of vitamin E to volunteers increased the alpha-tocopherol content of the
erythrocytes and decreased the susceptibility of the latter to the hemolytic
action of cobra and viper venoms. Further, exogenous addition of graded amounts
of alpha-tocopherol to the red cells, prior to the addition of either venoms,
minimizes the venom-induced lysis and erythrocyte phospholipid splitting. It may
thus be inferred that vitamin E, a fat-soluble antioxidant, plays an important
role in reducing the hemolytic action of cobra and viper venoms.
PMID- 9643480
TI - Interactions between bacterial toxins and intestinal cells.
AB - Bacterial toxins which act on intestinal cells display a great diversity of size,
structure and mode of action. Some toxins interact with the cell by transducing a
signal across the membrane leading to stimulation of intracellular second
messenger (E. coli heat stable enterotoxin), others form pores (C. perfringens
enterotoxin, ...) permitting the leakage of cellular components and cell lysis.
The most sophisticated toxins comprise at least two functional domains or
components, one being a binding domain permitting the internalization into the
cell of an enzymatic domain which modifies an intracellular target. The enzymatic
modification (ADP-ribosylation, UDP-glucosylation, glycohydrolysis, proteolysis,
...) of a specific target (heterotrimeric G-protein, small G-protein, monomeric
actin, ribosomal RNA, ...) alters the cell physiology (increase of ions and water
secretion, cytoskeleton rearrangement, protein synthesis inhibition, apoptosis,
...) and tissue organization (modification of barrier permeability, necrosis,
...). The study of bacterial toxins leads to the understanding of the
interactions between pathogenic bacteria and their hosts and constitutes also a
new approach in cell biology, by facilitating the exploration of certain
regulatory pathways such as that controlling actin polymerization.
PMID- 9643482
TI - Bibliography of toxinology.
PMID- 9643481
TI - Inhibitory effect of habu antivenom on fibrinopeptide A release induced by
Trimeresurus flavoviridis crude venom.
AB - The correlation between the clotting activity of crude venom and concentration of
fibrinopeptide A (FPA) released by the crude venom in rabbit plasma was evaluated
and expressed as the coefficient of correlation (r = 0.850). The venom-induced
FPA release was inhibited by habu antivenom. For such inhibition of FPA release,
the correlation between the concentration of habu antivenom (Y) and that of crude
venom (X) could be expressed by the equation Y = 7.115 + 0.709X. An absence of
venom-induced FPA release in rabbit plasma had suggested that the clotting
activity of crude venom could be neutralized by the habu antivenom. It is
suggested that determinations of the FPA level in the plasma are effective in
providing an indication of the reliability for serotherapy using habu antivenom.
PMID- 9643483
TI - Fat necrosis in surveillance biopsies of heart transplants.
AB - Fat necrosis was observed in surveillance biopsies of five patients following
heart transplant. This reaction is poorly documented in the literature, but in
personal communication, some pathologists working in the field have had
experience with it. Four of the cases developed two to six days after
transplantation, but in the fifth case, fat necrosis developed ten months after
transplantation. Autopsy study of one case showed extensive severe fat necrosis
involving both donor and recipient tissues. The cause is not known, and the
changes are independent of rejection. However, the fat necrosis can be found
within the interstitial tissues of the myocardium and subendocardium and may be
mistaken for rejection if lymphocytes and polymorphs are part of the inflammatory
response. The only clinical finding thought to be related to the fat necrosis was
the development of transient complete heart block in a patient in whom the
International Society for Heart and Lung Transplantation (ISHLT) standardised
rejection grading was never greater than IA.
PMID- 9643484
TI - Public attitudes towards the autopsy in China.
AB - The autopsy rate in China has fallen within the last few years. The attitudes of
the public have become an important factor for its decline. Attitudes towards
autopsy were surveyed from 400 subjects residing in the 27 provinces of China.
Among the 299 survey forms returned, 284 were completed correctly, the remaining
15 being incomplete. The response rate was 71%. More than half of the responding
members considered autopsy beneficial. However their perception of autopsy was
quite inaccurate and prejudicial, lacking complete information. The two most
frequent reasons for not accepting an autopsy were the lack of awareness towards
the practice of autopsy and the wariness of body disfigurement after the autopsy
was performed. It was suggested that the most appropriate way to change public
perception of autopsy was through education. The primary tool for reaching the
public was through the media. In addition, the approach to obtaining consent for
autopsy should be improved.
PMID- 9643485
TI - Intracranial epithelioid hemangioendothelioma arising at site of previously
excised atypical meningioma.
AB - Epithelioid hemangioendothelioma is an uncommon vascular tumor which, in most
cases, pursues a clinical course intermediate between hemangioma and
angiosarcoma. Only four completely documented cases of central nervous system
involvement by this tumor appear in the literature. We present an additional
case, which is remarkable in its occurrence at the site of a previously excised
atypical meningioma and in its unusually aggressive clinical course. To our
knowledge this is the first report of intracranial epithelioid
hemangioendothelioma with postmortem documentation. The patient initially
presented with a 7 cm right post frontal tumor; an atypical meningioma was
excised and removal appeared complete on immediate post-operative scans. Seven
months later the patient re-presented with tumor recurrence at the previous
operative site; a second craniotomy was performed and, on this occasion, the
excised tumor had the histological features of an epithelioid
hemangioendothelioma without evidence of meningioma: both morphologically and
immunohistochemically the two tumors were quite distinctive. Further recurrence
prompted radiotherapy but the patient continued to deteriorate and died five
months later. Massive recurrence of intracranial tumor was found at postmortem
examination.
PMID- 9643486
TI - The value of histological examination in the audit of hospital autopsies: a
quantitative approach.
AB - The aims of this study were to compare the clinical with autopsy diagnoses, to
evaluate the role of histological examination in the pathological diagnoses and
to assess the new pathological diagnoses uncovered by autopsy. We aimed to obtain
quantitative assessment of the sensitivity, specificity and accuracy of clinical
diagnoses. The guidelines for postmortem reports by the Royal College of
Pathologists (1993) were implemented for reports used in this study. These
guidelines are similar in intent to those of the College of American
Pathologists. Complete macroscopic and histological studies of 108 (53 females)
autopsies were analysed. The mean age was 78.0+/-9.0 (SD) years (range 54-94
years). The interquartile range (25%ile 75%ile) was 72-84 years, with a median of
79.5 years. Seventy per cent of all causes of death were confirmed by
macroscopical and histological examination. Sixty-one clinical diagnoses were
inconsistent with the pathological findings. Histological examination contributed
significantly to the final diagnosis in major (5%) and minor (6%)
clinicopathological as well as new pathological findings (23%). The most common
causes of death not suspected clinically were pulmonary embolism (23%),
bronchopneumonia (22%), ischemic heart disease (13%) and malignancies (10%). The
clinical sensitivity of antemortem diagnoses was 25% for peritonitis and 24% for
pulmonary embolism. The overall clinical sensitivity was 54% and specificity 92%.
The accuracy of positive diagnosis was 69% and accuracy of negative diagnosis
88%. Unexpected causes of death represented a third of all causes of death
reported. Histological examination is an important tool in hospital autopsy
audit. A quantitative approach can be used to assess the accuracy of postmortem
clinical diagnoses, to identify the possible source of clinical diagnostic
weakness, and provide data that may be of use for diagnostic precision in the
more difficult clinical subjects.
PMID- 9643487
TI - Tumor microvascularity has no independent prognostic significance for breast
cancer.
AB - There is a continuing controversy regarding the value of estimating degree of
intra-tumor vascularity to predict prognosis in breast cancer. In order to
resolve this controversy, primary tumors from a cohort of 519 women with breast
cancer were analysed to determine whether association exists between degree of
vascularity and prognosis. Tumor vascularity was estimated by
immunohistochemistry using a monoclonal antibody to the antigen CD31. The tumor
area showing the highest degree of vascularity was chosen to score the number of
microvessels per unit area. Issues such as the reproducibility of the
microvascularity score and its association with tumor parameters including size,
histological grade and hormone receptor levels were investigated. Although
previously agreed criteria were used, consensus between two pathologists'
estimations of the degree of vascularity was only moderate. There was no
statistically significant association between tumor vascularity score and other
currently established parameters of prognosis. After a median follow up of 71
months for axillary node negative patients, there was no association between
tumor vascularity score and increased risk of relapse or death from breast
cancer. In axillary node positive patients, tumor vascularity score was
associated with increased risk of relapse and death from breast cancer. This
association was not however independent of other established parameters of
prognosis.
PMID- 9643488
TI - Thymic carcinoma: spectrum of differentiation and histologic types.
PMID- 9643489
TI - Atypical subcutaneous fatty tumors: a review of 37 referred cases.
AB - We reviewed 37 referred, atypical, subcutaneous fatty tumors. There was a male
preponderance (28:9). The median age was 51.5 years (26-83); the median duration
of symptoms was 18 months (three weeks to 35 years); the median size was 5.5 cm
(1.5-20) and the posterior cervico-dorsal areas (17 cases) was the commonest
location. We divided tumors into five histological categories: (1) subcutaneous
fibrolipomas with slight fibroblastic atypia (five cases); (2) subcutaneous
spindle cell lipomas with atypia (mixed spindle cell/pleomorphic lipomas) without
lipoblasts (three cases); (3) subcutaneous atypical well-differentiated fatty
tumors (pure pleomorphic lipomas) without lipoblasts (nine cases); (4)
subcutaneous atypical well-differentiated fatty tumors (pleomorphic lipomas) with
lipoblasts (17 cases); (5) subcutaneous atypical fatty tumors with poorly
differentiated or de-differentiated areas (three cases). Follow-up information
was obtained in 25 cases (68%). The follow-up times were from three to 192 months
(median 31). Five tumors (20%) recurred, two as the same and three as a higher
histological category. Two were originally referred because of a recurrence. Four
recurred once and one, initially a category 4 tumor, recurred twice as a category
5 tumor. Two category 1 and three category 4 tumors recurred. There were no
recurrences in the other three groups. All recurrent tumors were located outside
the cervico-dorsal areas. The sizes of two tumors that recurred were 2.8 and 3 cm
and the time to first recurrence was from one to 85 months. Two recurrent tumors
of high histological category were controlled by re-excision and either
radiotherapy or combined chemotherapy and radiotherapy. This series suggests that
atypical subcutaneous fatty tumors comprise a continuous and potentially
transforming histological spectrum, which ranges from mildly atypical
fibrolipomas through various mixed spindle cell and pleomorphic lipoma patterns
to tumors indistinguishable from de-differentiated liposarcomas. Despite a
sometimes alarming histological appearance, none in the present series
metastasized.
PMID- 9643490
TI - Diagnostic value of p53 immunohistochemistry in Barrett's esophagus: an
endoscopic study.
AB - The aim of this study was to establish the diagnostic utility of p53
immunohistochemistry in Barrett's esophagus. Three pathologists reviewed
endoscopic biopsy specimens and one surgical specimen derived from 102 subjects
in a prospective follow-up series. Dysplasia was graded as negative, indefinite,
low grade and high grade. p53 staining was assessed as negative, weak or patchy
and strong. Kappa coefficients for interobserver agreement for the three
combinations of observer pairs were moderate to substantial (0.48, 0.55 and 0.68)
for dysplasia and substantial to near perfect (0.77, 0.82 and 0.89) for p53
immunostaining. In the consensus grading achieved for dysplasia, strong p53
staining was recorded in 0/79 samples that were negative or indefinite for
dysplasia, 5/15 (33%) examples of low grade dysplasia and 7/8 (87%) examples of
high grade dysplasia. Non-dysplastic p53 positive glands were seen in specimens
from two subjects harbouring dysplasia or cancer elsewhere. Two p53 positive
specimens were, upon review and discussion, re-assigned from low- to high-grade
dysplasia. It is concluded that p53 immunohistochemistry facilitates the
interpretation of Barrett's epithelium but need only be employed to confirm a
suspected diagnosis of dysplasia and assist with the distinction between low- and
high-grade dysplasia.
PMID- 9643491
TI - Broadsheet number 43: The role of the laboratory in the investigation and
management of hyperuricemia.
PMID- 9643492
TI - Broadsheet number 44: Rickettsial diseases: the Australian story so far.
PMID- 9643493
TI - Test and teach. Number eighty seven: hepatic angiomyolipoma.
PMID- 9643494
TI - Test and teach. Number eighty eight: alveolar capillary dysplasia.
PMID- 9643495
TI - Test and teach. Number eighty nine: gastrointestinal autonomic nerve tumor
(GANT).
PMID- 9643496
TI - Aggressive natural killer cell leukemia/lymphoma.
AB - A 32 year old Caucasian male presented with fever, massive hepatosplenomegaly and
lymphadenopathy. Peripheral blood and bone marrow findings were consistent, both
morphologically and immunophenotypically, with a natural killer cell
leukemia/lymphoma. The disease was rapidly progressive and was fatal within five
days after presentation.
PMID- 9643497
TI - The prevalence and age distribution of human thymic B lymphoid follicles.
AB - The reported prevalence of B lymphoid follicles in the normal human thymus
differs widely between studies. In this histological study we have estimated the
prevalence of these follicles, allowing for two factors which we believe may be
largely responsible for such differences. One is the effect of stress of more
than 48 hours duration, which has been shown to be associated with a decrease in
prevalence, and the other is the considerable differences in prevalence found in
different age groups. The 639 thymuses in this study were selected from
individuals who died less than 48 hours after the onset of their fatal condition.
No individuals with autoimmune diseases were included. The study group was
divided into age groups to demonstrate the age related variations in prevalence.
The follicles were identified by their morphology and by their reactivity with
the B lymphoid cell marker L26. No follicles were found in the thymuses of
infants in the first year of life. However the prevalence rose rapidly thereafter
to a peak of 93% in individuals the first half of the second decade then
gradually declined to only 9% in individuals older than 60 years. (The prevalence
in young adults being approximately equal to that reported in young adults with
autoimmune diseases.) It seems likely therefore that a considerable amount of the
variation in prevalence found in previous studies is related to the inclusion in
those studies of thymuses modified by stress as well as the grouping together of
different age groups with differing naturally occurring prevalences of B lymphoid
follicles. We concluded that B lymphoid follicles occur frequently in the
thymuses of healthy individuals, that their prevalence varies considerably with
age and that their mere presence should not be accorded any pathological
significance.
PMID- 9643498
TI - Detection and characterisation of extended spectrum beta-lactamases in Klebsiella
pneumoniae causing nosocomial infection.
AB - One hundred and ninety-five multi-resistant strains of Klebsiella pneumoniae were
isolated at Princess Alexandra Hospital (PAH) between December 1991 and June
1995. All these organisms produced extended spectrum beta-lactamases (ESBLs) as
detected by the double disc synergy test (DDST). Between June 1994 and June 1995,
a second population of 67 multi-resistant but DDST negative strains was isolated.
Twenty multi-resistant Klebsiella pneumoniae strains (16 DDST positive and four
DDST negative) and one susceptible strain were selected for further study. These
were tested for production of ESBLs by two double disc synergy methods and agar
dilution minimum inhibitory concentrations (MICs) with and without clavulanic
acid. Detected ESBLs were further characterised by isoelectric focusing. The
confirmed DDST positive K. pneumoniae strains all produced ESBLs that focused at
an isoelectric point (pI) of 7.6, suggesting the presence of SHV-2, SHV-2a, SHV
6, SHV-7 or SHV-8 enzymes. The multi-resistant DDST negative strains showed no
clavulanic acid synergy and thus no evidence of the presence of ESBLs.
PMID- 9643499
TI - Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian
patients.
AB - Chlamydia pneumoniae is a recently reported, but common, respiratory tract
pathogen. The organism has been detected by electron microscopy,
immunocytochemistry, polymerase chain reaction (PCR) and recently culture within
atherosclerotic plaques, suggesting a possible association between C. pneumoniae
infection and atherosclerosis. Interestingly this association has not been found
by all researchers. We examined 17 carotid endarterectomy specimens, 16 carotid
arteries and 16 coronary arteries from autopsy specimens. They were examined by
PCR for the presence of C. pneumoniae. In none of the 49 atherosclerotic samples
examined was C. pneumoniae detected. The sensitivity of our PCR assay was
rigorously tested and found to detect consistently fewer than ten elementary
bodies. The association between C. pneumoniae and atherosclerosis is intriguing
but has not yet been demonstrated in Australian patients.
PMID- 9643500
TI - Effect on organism recovery rate from BacT/Alert blood cultures with reduced
incubation period.
AB - This retrospective study evaluated 15,377 sets of BacT/Alert blood cultures to
determine incubation time for blood cultures. Ninety-six per cent (1476) of total
isolates signalled positive within five days and 56 isolates turned positive in
five to seven days. Of the 56 organisms recovered between five and seven days, 49
were considered contaminants and seven were considered clinically significant. On
assessing the medical records of the patients with the seven clinically
significant isolates, it was determined that the clinical outcome would not have
changed if these isolates were missed. We conclude that a five day incubation
protocol reduces the recovery of skin contaminants while not significantly
decreasing the recovery of clinically significant organisms. The data suggest
that the incubation time can be further reduced but this policy will depend on
the individual institution and their patient population mix.
PMID- 9643501
TI - An evaluation of the Behring Diagnostics Enzygnost Syphilis enzyme immunoassay.
AB - The Enzygnost Syphilis (Behring Diagnostics, Marburg, Germany) was evaluated (i)
using sera already characterised using the rapid plasma reagin test and the
Treponema pallidum hemagglutination test (TPHA); (ii) prospectively; (iii) using
sera which are recognised as causing "problems" with enzyme immunoassays. The
Enzygnost Syphilis was found to have a reproducibility of 98.6% and a sensitivity
of 99.5% using sera known to be TPHA-reactive. When tested prospectively, the
false reactive rate was 3.2%. These results show that the assay performs
sufficiently satisfactorily for its introduction as a screening assay for
evidence of syphilis infection in our population.
PMID- 9643502
TI - Evaluation of bacteriological transport swabs.
AB - Ten commercial transport swabs were evaluated for their ability to preserve
bacteria for 24 and 48 hours. Microorganisms included ATCC strains of Gram
positive and Gram-negative aerobes and anaerobes. There was a wide variation in
performance. Swabs using Amies plus charcoal medium or Stuart's medium had better
recovery rates than those using Amies medium alone. The nature of the tips of the
swabs had little influence. Performance was not correlated with cost of the
swabs. These data will assist institutions to make cost-effective decisions when
purchasing bacteriological transport systems.
PMID- 9643503
TI - Comparison of culture, histopathology and urease testing for the diagnosis of
Helicobacter pylori gastritis and susceptibility to amoxycillin, clarithromycin,
metronidazole and tetracycline.
AB - Gastric biopsy specimens were taken from 737 patients undergoing upper
gastrointestinal endoscopy and assessed for Helicobacter pylori infection. The
diagnostic utilities of H. pylori culture (733 patients), detection of urease
production (724 patients) and histopathological examination (469 patients) were
compared. Since each of these techniques may fail to diagnose patients infected
with H. pylori, an attempt was made to estimate the true rate of infection using
a mathematical approach that combined the results of culture, histopathology and
urease testing; 34% of the 733 patients were thought to be infected. Using this
figure as a benchmark, the sensitivity, specificity, positive predictive value
and negative predictive value of H. pylori culture were 73.2%, 100%, 100% and
86.3%, respectively, compared with 58.7%, 100%, 100% and 89.6%, respectively for
urease production and 77.0%, 100%, 100% and 82.4%, respectively for
histopathology. Thus, histopathological examination was the single most reliable
test. A combination of histopathological examination and H. pylori culture
diagnosed 99.5% of patients that were estimated to be truly infected. The minimum
inhibitory concentrations of a number of antibiotics were measured for 135
isolates of H. pylori. All isolates were susceptible to amoxycillin and
tetracycline whereas 5.2% were resistant to clarithromycin and 60% were resistant
to metronidazole.
PMID- 9643504
TI - Detection of decreased penicillin susceptibility in viridans group streptococci.
AB - One hundred consecutive clinically significant viridans group streptococcal
isolates had their susceptibility to penicillin determined by the penicillin E
test method. The ability of penicillin 2 and 10 unit disks and the oxacillin 1
microg disk to detect reduced penicillin susceptibility, ie; MIC > or = 0.25
microg/ml, in viridans group streptococci was determined by comparing the zone
diameters against the penicillin E-test MICs. The sensitivity, specificity and
predictive values of previous, existing and proposed interpretative criteria to
detect decreased penicillin susceptibility were determined. Thirty-seven per cent
of the isolates had reduced susceptibility to penicillin. The previous 1993 NCCLS
interpretative criteria for the penicillin 10 unit disk, ie; resistant < or = 27
mm failed to detect 16 of 37 (43%) isolates with reduced penicillin
susceptibility. The 1 microg oxacillin disk using existing meningococcal
interpretative criteria, ie; resistant < or = 10 mm, failed to detect 11 of 37
(40%) isolates with reduced penicillin susceptibility. When the oxacillin 1
microg disk pneumococcal interpretative criteria were used, ie; resistant < or =
19 mm, all the isolates with reduced penicillin susceptibility were detected but
42 of 63 (67%) susceptible isolates were misclassified as resistant. Based on our
data, we set new interpretative criteria to detect all isolates with decreased
penicillin susceptibility for each of the three disks. Using our proposed zone
diameters to detect decreased penicillin susceptibility of < or = 27 mm for the
penicillin 2 unit disk, < or = 35 mm for the penicillin 10 unit disk, and < or =
17 mm for the oxacillin disk, 34 (54%), 44 (70%),and 21 (33%) of the 63
susceptible isolates, respectively, were misclassified as having decreased
penicillin susceptibility. Our data show that the oxacillin 1 microg disk is able
to detect decreased susceptibility to penicillin in viridans group streptococci
with greater specificity than either penicillin 2 or 10 unit disks.
PMID- 9643505
TI - Hepatitis C genotyping by direct sequencing of the product from the Roche
AMPLICOR test: methodology and application to a South Australian population.
AB - The Roche AMPLICOR RT-PCR amplifies a 244 nucleotide sequence within the 5' non
coding region (5'NCR) of the viral genome and is a widely used commercial test
for the qualitative determination of hepatitis C RNA from sera. This paper
describes a routine procedure for the purification of the PCR product, and its
use in automated DNA sequencing, for determining the genotype of hepatitis C
virus (HCV) isolates. Direct sequencing of the purified product was possible for
86% of samples, whilst 14% required additional amplification using a nested PCR
method in order to read the resulting electropherogram. This method of genotyping
is considerably less expensive than currently available commercial kits, and is
convenient for the increasing number of laboratories that have access to
automated DNA sequencers. The highly conserved nature of the 5'NCR limited
differentiation of types and subtypes to an extent comparable to commercial HCV
typing methods. Using this method on available laboratory samples and on patients
about to commence interferon therapy, we found a predominance of genotype 1 (59%)
and 3a (31%). Analysis of data on the interferon patients showed the median
length of time from first exposure to diagnosis to be significantly longer for
patients with genotype 1 than genotype 3a.
PMID- 9643506
TI - The molecular genetics of central nervous system tumors.
AB - Over the past few years, although much has been learned about the molecular
genetics of central nervous system (CNS) tumors, researchers and pathologists are
only beginning to understand the scientific basis of the development of these
tumors. Data accumulated so far support the division of glioblastoma into two
clinical and molecular subsets. Primary or de novo glioblastomas occur in older
patients, are clinically aggressive and exhibit epidermal growth factor receptor
amplification or overexpression. Secondary glioblastomas develop from pre
existing low-grade astrocytomas, have a more protracted clinical course, and
frequently contain p53 mutations. Both types of tumors show deletions of
chromosome 10 and possibly mutations of the PTEN/MMAC1 gene as an endstage event.
Oligodendrogliomas have been shown to have genetic abnormalities distinct from
those of the astrocytic tumors, commonly involving chromosomes 1p and 19q. As
regards meningiomas, loss of chromosome 22q and mutations of the
neurofibromatosis type 2 gene are frequent events and loss of chromosome 14q and
10q may be seen in atypical or malignant transformation. Such genetic findings,
apart from providing a better understanding of neoplastic transformation in brain
tumors, are beginning to form the basis of a new approach to neuro-oncology.
PMID- 9643507
TI - A mucosa-associated lymphoid tissue (MALT) type lymphoma (marginal zone B-cell
lymphoma) from the palatine tonsil.
AB - The clinicopathologic and immunologic features of a low-grade B-cell non
Hodgkin's lymphoma that arose in the palatine tonsil are presented here. The
histologic findings were similar to the mucosa-associated lymphoid tissue (MALT)
type lymphoma described in the gastrointestinal tract and glandular tissues. The
histogenesis, differential diagnoses and classification of these tumors are
briefly discussed in the light of recent findings and proposals by the
International Lymphoma Study Group (ILSG). A literature survey revealed that MALT
lymphomas are exceptionally rare in Waldeyer's ring. Pathologists should be aware
of the possible occurrence, albeit rare, of this tumor when confronted with a low
grade B-cell lymphoma from Waldeyer's ring.
PMID- 9643508
TI - Folliculosebaceous cystic hamartoma.
AB - Although folliculosebaceous cystic hamartoma (FCH) is an uncommon cutaneous
entity with distinct classical and variant histopathologic features, it lacks
distinctive typifying clinical features. Since the original description of five
cases of FCH by Kimura et al. in 1991, 12 cases have been documented. We report a
further case of FCH presenting as facial lesion in a 35 year old African male.
FCH comprises prominent epithelial and mesenchymal components. The epithelial
component is characterised by folliculosebaceous proliferation with cyst-like
infundibular dilatation, and the mesenchymal component exhibits variable
fibroplasia, vascular and neural proliferation and adipocyte metaplasia.
Awareness of the lesion is important to avoid confusion with other cystic or cyst
like cutaneous lesions that contain prominent epithelial folliculosebaceous and
variable mesenchymal components.
PMID- 9643509
TI - Atypical cervical polyp with intracytoplasmic inclusions.
AB - Benign polyps containing atypical stromal cells are described at many anatomical
sites and some such lesions have been shown to contain intracytoplasmic actin
rich inclusions, believed to represent deranged filament metabolism in
proliferating myofibroblastic cells. We present a case of an atypical cervical
polyp with intracytoplasmic inclusions, occurring in a 23 year old female, and
provide support for the proposal that these inclusions are composed of actin
filaments, identical to those initially reported in infantile digital
fibromatosis. This report emphasises the need to recognise the benign nature of
such stromal proliferations and expands the range of myofibroblastic lesions in
which actin inclusions may occur. Characterisation of the inclusions will provide
further insight into the complexities of actin metabolism.
PMID- 9643510
TI - Intraductal carcinoma of the prostate metastatic to the penile urethra: a rare
demonstration of two morphologic patterns of tumor growth.
AB - Penile metastases from prostate cancer are rare and are usually a manifestation
of wide-spread cancer dissemination. Isolated urethral metastases form a small
fraction of these cases, have a longer survival rate and may represent spread by
implantation following instrumentation. We report a case of prostatic carcinoma
presenting with an isolated metastasis to the penile urethra after
catheterisation and transurethral prostatectomy. The primary tumor had a
prominent intraductal component whose architectural features were mimicked in the
metastasis. The possible mechanisms of spread and the diverse appearances of
cancer associated with an intraductal component are discussed.
PMID- 9643511
TI - "Helicobacter pylori in areas of intestinal metaplasia in gastric antral mucosa",
by Misra et al.
PMID- 9643512
TI - Menopause, mood and hormone replacement therapy: methodological issues.
AB - In this paper a number of methodological issues relating to research on the
relationship between the menopause, mood and hormone replacement therapy (HRT)
are discussed. These issues relate to problems of design and statistical
analyses, problems which have prevented the reaching of definite conclusions
regarding the relationship between menopause, mood and hormones. These problems
are discussed under three main headings, namely, the assessment of menopausal
status, statistical modelling and the design and analyses of clinical trials.
Problems relating to concepts and measurement of dependent variables are the
subject matter of the papers that follow. Within the three main headings more
specific issues are detailed. The paper concludes with a list of recommendations
on how research in this important area might be further advanced.
PMID- 9643513
TI - The Blatt-Kupperman menopausal index: a critique.
AB - The Blatt-Kupperman menopausal index has been used widely in studies of
climacteric symptoms, but it now needs to be reassessed. The original index was
derived from clinical experience in New York in the 1950s. The index was a
combination of self report and physician ratings; it omitted measures of vaginal
dryness and loss of libido; no demographic data of the sample were given;
weighting was used without statistical justification; terms were ill defined;
categories included overlapping scores, and most importantly scores were summed
without being based on independent factors. Modern psychometrics has led to the
publication of reliable and valid scales. These should be used in climacteric
research in preference to the Blatt-Kupperman index.
PMID- 9643514
TI - Constructing a standard climacteric scale.
AB - Issues relating to the design of scales and their psychometric properties are
discussed in the context of constructing a standard measure of core climacteric
symptoms. Seven factor analytic studies of climacteric symptoms are examined to
determine whether or not there is sufficient consensus across studies to permit
agreement on the symptom content and the structure of such a scale. It is argued
that these factor analytic studies do indeed contain sufficient consensus on the
basis of which a standard climacteric scale can be constructed. Such a scale is
described.
PMID- 9643515
TI - The assessment of depression in peri-menopausal women.
AB - This paper reviews research methods for detecting and assessing depressive
symptoms in peri-menopausal women. The paper is written from the standpoint of
clinical psychiatrists and clinical psychologists. Problems of method arise in
two main areas: (i) the selection of population samples; (ii) the choice of
methods for defining, detecting and measuring depression. An important
distinction should be made between depressed mood and depressive disorder.
Depressed mood is familiar sadness, low spirits, or despondency. Depressive
disorder is a syndrome which is much more serious. The failure to make this
distinction can detract from research findings. Standardised measures should
always be used. These measures may be either self-rated or interviewer-rated. It
is emphasised that the choice of these measures should be based on four
characteristics: criterion overlap, sensitivity, test-retest reliability, and
utility. The scales already available can be valuable provided that they are
chosen carefully and with particular regard to these four qualities.
PMID- 9643516
TI - Methods of assessing the impact of climacteric complaints on quality of life.
AB - Quality of life is an important outcome that reflects the way patients feel and
function. Assessing the impact of a condition on quality of life is particularly
relevant in symptomatic conditions such as the menopause. A range of measurement
tools are available for monitoring how symptoms, typical of the climacteric
period, affect patients with regard to their well-being, sleep disturbance, other
somatic symptoms, cognitive function and sexual functioning. However, to gain a
valid assessment of quality of life and the effects of treatment in the
menopause, only standard and well-validated measurement tools should be used. The
appropriateness of relying on the use of psychiatric rating scales to assess mood
is questionable. Results obtained from an increasing number of controlled
clinical studies indicate that treatment with oestrogen, in addition to
alleviating vasomotor symptoms, can substantially improve patients' quality of
life.
PMID- 9643517
TI - Methodological problems in the study of sexuality and the menopause.
AB - Few studies have considered the effects of menopause on sexuality. Large studies
with representative samples using postal questionnaires have included only a few
sexual variables. More comprehensive studies have tended to employ non
representative samples that raise questions concerning generalization of
findings. Major problems in existing research have been: failure to collect data
on variables known to affect sexuality and/or failure to utilize such data in
analyses, studying only one, sometimes two, menopausal phases, gathering
retrospective data, asking subjects directly about the relationship of menopause
to sexuality, gathering too few sexual data, not providing a complete description
of sexual measures, neglecting to report methodology clearly and completely,
failing to evaluate data statistically, and inferring causation from
correlations. Evidence from existing research suggests a decline in sexual
interest, frequency of sexual intercourse, and vaginal lubrication in association
with the menopause. Findings for variables such as capacity for orgasm,
satisfaction with sex partner, and vaginal pain or discomfort are few and mixed.
PMID- 9643518
TI - Aspects of progestin activity on the breast. European Progestin Club.
AB - On 9-11 May 1997, the second Meeting of the European Progestin Club was held in
Turin, Italy. Aspects of progestin use on the breast were discussed, based on the
currently available scientific data. The paper covers topics addressed at the
meeting and summarizes the recommendations which could be agreed on by the
participants.
PMID- 9643519
TI - Hormone replacement therapy usage: a 10 year experience of a solo practitioner.
AB - The objective of this study was to identify factors affecting hormone replacement
therapy (HRT) usage among patients of a single physician. All active patients (n
= 330) given a HRT prescription over the past 10 years (1985-1995) by the
physician were sent a questionnaire on health knowledge, lifestyle patterns,
general medical and reproductive histories, responses to HRT usage and decision
making about HRT use. A total of 214 useful questionnaires were returned giving a
response rate of 65%. For this cohort, the length of HRT use for those still
taking HRT was 60 months; and for those no longer taking HRT, it was 32 months;
and 85% of those ever given an HRT prescription were still using HRT at the time
of survey. The educational backgrounds, exercise patterns, health knowledge,
medical and reproductive histories of this group were representative of those
found among suburban postmenopausal women in central Pennsylvania. Among this
cohort, the most important reason for them taking HRT was the physicians'
recommendation.
PMID- 9643520
TI - Facial wrinkling in postmenopausal women. Effects of smoking status and hormone
replacement therapy.
AB - BACKGROUND: There is some evidence that hormone replacement therapy may produce
significant improvements in fine wrinkling, while aging skin is more frequently
found in smokers. However, studies of the combined effect of a protective factor,
such as HRT, and a damaging factor, such as smoking, are rare. OBJECTIVES: To
determine in postmenopausal women the relationship between smoking status and the
average number of packets of cigarettes since the subject took up smoking (packs
years) on the one hand, and facial wrinkling on the other, and to evaluate the
role of hormone replacement therapy in the prevention of wrinkles in smokers and
non-smokers. METHODS: All subjects were recruited from our menopause clinic at
Hospital Clinic i Provincial in Barcelona and were placed into one of three
groups according to their smoking status: 215 life-long non-smokers, 306 former
smokers and 209 current smokers. Smoking status, pack-years and hormone
replacement were assessed by direct questioning. Facial wrinkle scores were
estimated by standardized visual assessment. RESULTS: The relative risk of
moderate-severe wrinkling for current smokers compared to that for life-long non
smokers was 2.57 (confidence interval: 1.83-3.06; P < 0.0005). Pack-years was
positively related to facial wrinkles. Life-long non-smokers receiving HRT had
lower facial wrinkle scores than Life-long non-smokers who had never received
HRT. HRT did not, in general, modify the facial wrinkle score in current smokers.
CONCLUSION: Our results suggest that the risk of facial wrinkles is greater in
smokers and that HRT does not diminish this risk.
PMID- 9643521
TI - Sex-hormone binding globulin as an indicator of the hepatic impacts of continuous
combined hormone replacement regimens.
AB - OBJECTIVES: Nonoral administration of hormone replacement therapy avoids the
first pass metabolism of steroids in the liver. We wanted to determine to what
extent it has an effect on the serum concentrations of sex-hormone binding
globulin and the free testosterone index. METHODS: Postmenopausal women received
50 microg per day transdermal estradiol associated with the use of a
levonorgestrel-releasing intrauterine device (20 women) or a daily oral dose of 2
mg of estradiol and 1 mg of norethisterone acetate (20 women) for 1 year. Eight
women, five in the nonoral and three in the oral therapy group discontinued the
study. RESULTS: Although serum sex-hormone binding globulin concentrations
decreased in women receiving transdermal estradiol in combination with a
levonorgestrel-releasing intrauterine device, the free testosterone index did not
change significantly. In the continuous oral regimen, no significant changes in
serum sex-hormone binding globulin or free testosterone index were observed. The
free testosterone index, however, was significantly higher in the nonoral therapy
group after 6 and 12 months of treatment than in the oral therapy group.
CONCLUSIONS: Continuous progestin combined with continuous estrogen in oral and
nonoral replacement therapy does not lead to a substantial androgenic excess in
postmenopausal women. The intrauterine administration of levonorgestrel appears
to have some hepatic effect.
PMID- 9643522
TI - Reduction of intraocular pressure in a glaucoma patient undergoing hormone
replacement therapy.
AB - OBJECTIVES: To show the reducing effect of estrogens and progestins on the
elevated intraocular pressure (IOP) in the case of a 56-year-old woman showing
typical climacteric complaints, who was admitted to the menopause outpatient
unit. She also suffered from a primary open-angle glaucoma treated with
betaophtiole eye drops with intraocular pressures of 16-20 mmHg under this local
therapy. METHODS: IOP patterns were monitored by means of standardised daily
pressure profiles four times a day before as well as 4 and 12 weeks after the
beginning of hormone replacement therapy (HRT). The local glaucoma therapy
remained unchanged. RESULTS: During HRT, IOP levels were reduced from 16-20 mmHg
before therapy to 12-15 mmHg at week 4 and to 13-15 mmHg at week 12 after the
beginning of HRT. CONCLUSION: The finding of a close chronological relationship
between the onset of menopause and the development of a glaucoma is a potentially
new indication for HRT.
PMID- 9643523
TI - Multiple myeloma: VI International Workshop, June 14-18, 1997, Boston,
Massachusetts, USA.
AB - The VI International Workshop on Multiple Myeloma was organised by Professor
Kenneth C Anderson, Dana Farber Cancer Institute, and held on June 14-18, 1997,
in Boston, MA, USA. More than 500 participants from all over the world joined
this workshop. Several subjects were introduced and one of the most exciting
items of news was the identification of Kaposi's sarcoma-associated herpes virus
in the bone marrow stromal cells of patients with MM. The aim of this overview is
to give a glimpse of the subjects discussed and the statements made.
PMID- 9643524
TI - Primary fallopian tube cancer: a review of the literature.
PMID- 9643525
TI - Programmed cell death: the influence of CD40, CD95 (Fas or Apo-I) and their
ligands.
AB - Programmed cell death (PCD) or apoptosis is a process whereby developmental or
environmental stimuli activate a specific series of events that culminate in cell
death. PCD is essential for normal development and abnormality in the process can
lead to defects ranging from embryonic lethality and tissue-specific perturbation
of postnatal development to a high susceptibility to malignancy. Therapeutics
that modulate the regulation of PCD may provide a new opportunity for the
treatment of the PCD related diseases and cancer. CD40 and CD95 (Fas/Apo-I) are
transmembrane proteins of the nerve growth factor/tumour necrosis factor alpha
receptor superfamily. The death signal of PCD occurs when the CD95 receptor on
the cell surface binds to the CD95 ligand (CD95L) or to the anti-CD95 monoclonal
antibody (mAb). In contrast, PCD could be inhibited by the survival signal
mediated from the binding of the CD40 receptor to the CD40 ligand (CD40L) or to
the anti-CD40 mAb. In this review, the interaction of CD40/CD40L and CD95/CD95L
on PCD in normal and malignant cells is discussed.
PMID- 9643526
TI - How do mutated oncogenes and tumor suppressor genes cause cancer?
AB - In recent decades we have been given insight into the process that transforms a
normal cell into a malignant cancer cell. It has been recognised that malignant
transformation occurs through successive mutations in specific cellular genes,
leading to the activation of oncogenes and inactivation of tumor suppressor
genes. The further study of these genes has generated much of its excitement from
the convergence of experiments addressing the genetic basis of cancer, together
with cellular pathways that normally control important cellular regulatory
programmes. In the present review the context in which oncogenes and tumor
suppressor genes normally function as key regulators of physiological processes
such as proliferation, cell death/apoptosis, differentiation and senescence will
be described, as well as how these cellular programmes become deregulated in
cancer due to mutations.
PMID- 9643527
TI - Treatment of chronic myelogenous leukaemia.
PMID- 9643528
TI - Cancer morbidity in psychiatric patients: influence of lithium carbonate
treatment.
AB - The relationship between mental diseases and cancer development has been examined
in a number of studies but the findings are still inconclusive and suffer from
methodological problems. Studies conducted to examine the effect of lithium on
malignant cells yielded inconsistent results. The study group included 609
patients treated by lithium carbonate and 2396 controls. A lower but non
significant risk (RR = 0.79; CI = 0.17-3.60) to develop non-epithelial tumors was
found among lithium carbonate treated psychiatric patients as compared to
controls. A significantly (P = 0.05) inverse trend of cancer with lithium dose
was observed. The risk of cancer development among each group of psychiatric
patients was significantly lower than in the general population (RR = 0.68 for
the lithium treated group versus 0.78 for controls). Mental patients have a lower
cancer prevalence than the general population and lithium may have a protective
effect.
PMID- 9643529
TI - Inhibition of systemic TNF-alpha cytotoxicity in cancer patients by D
peptidoglycan.
AB - The current study was designed to investigate direct inhibitory effects of N
acetyl-glucosaminyl-muramyldipeptide (GMDP) over the cytotoxic nature of TNF
alpha. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-alpha
cytotoxicity was done in vitro on the following cell lines: A549 (human lung
carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer
cells). In a double-blind placebo-controlled trial, cancer patients with an
elevated activity of all five LDH isoensymes were randomized to receive either a
GMDP solution or a placebo; 63 patients were evaluated every third day for the
mean daily number of episodes of nausea or vomiting, changes in clinical status,
cell blood count and blood chemistry. A 95% inhibition of LDH release was noticed
on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72%
dose-dependent reduction in LDH activity. In vivo, LDH activity was decreased by
41% (+/-4%) (mean+/-SD) in all 21 subjects who were given 0.5-1.0 mg of GMDP
daily. A lowering of LDH activity by 73.4% (+/-4%) was observed in 23 patients
who received GMDP at a dosage of 1.5mg/kg daily. Correspondingly, a 10% (+/-2%)
increase in LDH activity was noticed in 19 patients who were given a placebo (P <
0.01). During the follow-up period, the overall clinical condition of all
patients treated with GMDP was improved. No side effects were observed. In nine
patients who experienced nausea from tumor toxicity before treatment, the symptom
subsided. In parallel, an extremely beneficial effect on lipids metabolism was
noticed in all patients with elevated cholesterol and trigliceride levels. A
dietary supplementation of GMDP has been shown to reduce systemic TNF-alpha
cytotoxicity during tumor shock.
PMID- 9643530
TI - Impact of histology on the treatment outcome of metastatic or recurrent renal
cell carcinoma.
AB - Among 107 renal cell carcinoma (RCC) patients with histopathologic subtype
diagnosis who were treated at Albert Einstein Cancer Center with cytokines over a
10-year period, seven patients had sarcomatoid histology, 63 had clear cell
carcinoma, and 10 patients had mixed histology (sarcomatoid and clear cell).
Regardless of their histology, patients with a disease free interval of 2 years
or more had significantly better survival. None of the patients with sarcomatoid
histology responded to therapy. However, several patients with mixed and clear
cell histology achieved partial or complete responses following high dose
Interleukin-2 (IL-2) therapy. The median survival of patients with sarcomatoid
histology was the shortest (13.8 months), whilst that of patients with mixed and
clear cell histology was much longer (34.8 months and 39.1 months, respectively).
This result was statistically significant in both univariate and multivariate
survival analysis (P < 0.001 and P < 0.01, respectively). Patients with mixed and
clear cell histology had no significant difference in survival, and their median
survival combined was significantly longer than that of patients with sarcomatoid
histology (P < 0.0001 in univariate analysis, P < 0.01 in multivariate analysis).
This study suggests that survival with a diagnosis of RCC is predicted by tumor
histology and disease free interval, and this impacts on the ability to respond
to standard therapy. Patients with mixed and clear cell histology respond to
cytokine therapy. Other therapies should be sought for patients with sarcomatoid
RCC.
PMID- 9643531
TI - Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide,
doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's
lymphoma.
AB - Protease inhibitors are an important new class of agents for the treatment of
human immunodeficiency virus (HIV) infection. The purpose of our trial was to
determine the feasibility of combining the protease inhibitor saquinavir with a
96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2),
doxorubicin (50 mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in
patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of
saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic
toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE
every 28 or more days. All patients received saquinavir (600mg PO TID),
filgrastim and Pneumocystis carinii and fungal prophylaxis. Patients also
received either stavudine (n = 2) or both stavudine and didanosine (n = 10).
Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and
the data were compared with the data from our prior study of CDE plus didanosine.
An interim analysis was performed after accrual of the first 12 patients in order
to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12
patients (67%) treated with CDE plus saquinavir compared with three of 25
patients (12%) in our prior study treated with CDE without saquinavir (P <
0.001). In logistic regression analysis, saquinavir use was the only factor
associated with a significantly greater risk of severe mucositis (relative risk
7.9; P = 0.03). Saquinavir use was not associated with a significant difference
in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose
reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes
for patients treated with saquinavir (absolute decrease of 23/microL, or a 26%
decrease from baseline) was significantly less than for patients treated without
saquinavir in the prior study (absolute decrease of 91/microL, or 42% decrease
from baseline; P = 0.05). Four of 10 patients (40%) treated with saquinavir had
an increase in CD4 lymphocytes of > or = 10/microL compared with none of 25
patients (0%) treated without saquinavir (P < 0.001). Combination of the protease
inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma
was associated with a significant increase in the incidence of severe mucositis.
This finding suggests that saquinavir may alter the metabolism of one of more of
the cytotoxic agents in the CDE regimen, and underscores the need for careful
investigation regarding the use of the protease inhibitors in patients receiving
chemotherapy.
PMID- 9643532
TI - Severe hypercalcaemia and extensive osteolytic lesions in an adult patient with T
cell acute lymphoblastic leukaemia.
AB - Hypercalcaemia is a rare feature of acute lymphoblastic leukaemia (ALL) in
adults, particularly of the T cell type. We report on a 24-year-old patient with
T-ALL, who presented with symptoms of hypercalcaemia (vomitus, acute renal
failure), bone pain, extensive osteolytic lesions and normal white cell count
without circulating blasts. An increased serum tumor necrosis factor (TNF-alpha)
concentration of 35 pg/ml was found; it remained elevated at 52 pg/ml four weeks
later, after having achieved haematological remission. Serum concentrations of IL
1beta, IL-6 and IL-2 were within the control range. The pathophysiology of
hypercalcaemia in malignancy and possible mediators of bone resorption, in
particular TNF-alpha, are discussed.
PMID- 9643533
TI - Solitary primary CNS lymphoma: long term survival following total resection.
AB - Primary non-Hodgkin's CNS lymphoma is rare, constituting 0.3-1.5% of all
intracranial neoplasms in patients without AIDS. In the past 10 years the
incidence has tripled in this population. The role of surgery is commonly limited
to obtaining adequate tissue for diagnosis. This has precluded the evaluation of
total surgical resection for a surgically accessible solitary lesion. We have
encountered a 36-year-old healthy white male with primary CNS lymphoma who is HIV
negative and who has survived over five years disease free after total surgical
resection of his lymphoma.
PMID- 9643534
TI - Successful treatment of cranial metastases of extrapulmonary small cell carcinoma
with chemotherapy alone.
AB - Extrapulmonary small cell carcinoma (EPSCC) is a distinct clinical and
pathological entity other than small cell carcinoma of the lung. We present a
case with EPSCC, with neurologic impairment due to brain metastases at initial
diagnosis, which showed a complete response to combination chemotherapy. A 55
year-old male patient was first admitted with a mass of 6 x 6 cm in diameter in
the right cervical region. The diagnosis of small cell carcinoma was entertained
with immunohistopathologic and light microscopic findings. During the period of
investigation the tumor showed rapid progression and the patient had neurologic
dysfunction with right hemiparesia, and papilla oedema in fundoscopy. Cranial CT
showed supratentorial multiple cranial metastases and peritumoral oedema. Since
the patient refused radiotherapy, combination chemotherapy was started (Etoposide
100 mg/sq m i.v., days 1,3,5 and cisplatin 80 mg/sq m i.v., day 1). A fast
response to the chemotherapy was observed with rapid disappearance of the
cervical mass. Following six cycles of the chemotherapy the patient recovered
fully and all the lesions disappeared with CT.
PMID- 9643535
TI - Foetal liver infusion in a chronic myeloid leukemia patient with busulphan
toxicity.
AB - A 36-year-old man suffering from chronic myeloid leukemia (in chronic phase) was
initially treated with busulphan. At the end of 6 months of follow-up he
developed bone marrow aplasia. He was given single foetal liver infusion therapy.
The patient recovered fully from aplasia. He continued in chronic phase for more
than 7 years with intermittent busulphan therapy.
PMID- 9643536
TI - TonB-dependent iron acquisition: mechanisms of siderophore-mediated active
transport.
AB - Cells growing in aerobic environments have developed intricate strategies to
overcome the scarcity of iron, an essential nutrient. In gram-negative bacteria,
high-affinity iron acquisition requires outer membrane-localized proteins that
bind iron chelates at the cell surface and promote their uptake. Transport of
bound chelates across the outer membrane depends upon TonB-ExbB-ExbD, a
cytoplasmic membrane-localized complex that transduces energy from the proton
motive force to high-affinity receptors in the outer membrane. Upon ligand
binding to iron chelate receptors, conformational changes are induced, some of
which are detected in the periplasm. These structural alterations signal the
ligand-loaded status of the receptor and, therefore, the requirement for TonB
dependent energy transduction. Thus, TonB interacts preferentially and directly
with ligand-loaded receptors. Such a mechanism ensures the productive use of
cellular energy to drive active transport at the outer membrane.
PMID- 9643537
TI - In search of higher energy: metabolism-dependent behaviour in bacteria.
AB - Bacteria use different strategies to navigate to niches where environmental
factors are favourable for growth. Chemotaxis is a behavioural response mediated
by specific receptors that sense the concentration of chemicals in the
environment. Recently, a new type of sensor has been described in Escherichia
coli that responds to changes in cellular energy (redox) levels. This sensor,
Aer, guides the bacteria to environments that support maximal energy levels in
the cells. A variety of stimuli, such as oxygen, alternative electron acceptors,
light, redox carriers that interact with the electron transport system and
metabolized carbon sources, effect changes in the cellular energy (redox) levels.
These changes are detected by Aer and by the serine chemotaxis receptor Tsr and
are transduced into signals that elicit appropriate behavioural responses.
Diverse environmental signals from Aer and chemotaxis receptors converge and
integrate at the level of the CheA histidine kinase. Energy sensing is widespread
in bacteria, and it is now evident that a variety of signal transduction
strategies are used for the metabolism-dependent behaviours. The occurrence of
putative energy-sensing domains in proteins from cells ranging from Archaea to
humans indicates the importance of this function for all living systems.
PMID- 9643538
TI - Target specificity of insertion element IS30.
AB - The Escherichia coli resident mobile element IS30 has pronounced target
specificity. Upon transposition, the element frequently inserts exactly into the
same position of a preferred target sequence. Insertion sites in phages, plasmids
and in the genome of E. coli are characterized by an exceptionally long
palindromic consensus sequence that provides strong specificity for IS30
insertions, despite a relatively high level of degeneracy. This 24-bp-long region
alone determines the attractiveness of the target DNA and the exact position of
IS30 insertion. The divergence of a target site from the consensus and the
occurrence of 'non-permitted' bases in certain positions influence the target
activity. Differences in attractiveness are emphasized if two targets are present
in the same replicon, as was demonstrated by quantitative analysis. In a system
of competitive targets, the oligonucleotide sequence representing the consensus
of genomic IS30 insertion sites proved to be the most efficient target. Having
compared the known insertion sites, we suppose that IS30-like target specificity,
which may represent an alternative strategy in target selection among mobile
elements, is characteristic of the insertion sequences IS3, IS6 and IS21, too.
PMID- 9643539
TI - The hexA gene of Erwinia carotovora encodes a LysR homologue and regulates
motility and the expression of multiple virulence determinants.
AB - We have identified a gene important for the regulation of exoenzyme virulence
factor synthesis in the plant pathogen Erwinia carotovora ssp. carotovora (Ecc)
and virulence and motility in Erwinia carotovora ssp. atroseptica (Eca). This
gene, hexA (hyperproduction of exoenzymes), is a close relative of the Erwinia
chrysanthemi (Echr) gene pecT and encodes a member of the LysR family of
transcriptional regulators. hexA mutants in both Ecc and Eca produce abnormally
high levels of the exoenzyme virulence factors pectate lyase, cellulase and
protease. In addition, Eca hexA mutants show increased expression of the fliA and
fliC genes and hypermotility. Consistent with a role as a global regulator,
expression of hexA from even a low-copy plasmid can suppress exoenzyme production
in Ecc and Eca and motility in Eca. Production of the quorum-sensing pheromone
OHHL in Ecc hexA is higher throughout the growth curve compared with the wild
type strain. Overexpression of Ecc hexA also caused widespread effects in several
strains of the opportunistic human pathogen, Serratia. Low-copy hexA expression
resulted in repression of exoenzyme, pigment and antibiotic production and
repression of the spreading phenotype. Finally, mutations in hexA were shown to
increase Ecc or Eca virulence in planta.
PMID- 9643540
TI - Replication strand preference for deletions associated with DNA palindromes.
AB - We have isolated and sequenced a set of deletions stimulated by DNA palindromes
in Escherichia coli. All of the deletions are asymmetric with respect to the
parental sequence and have occurred at short direct repeats. This is consistent
with deletion by strand slippage during DNA replication. The orientation of the
asymmetry in such deletion products is diagnostic of the direction of the strand
slippage event. It is therefore also diagnostic of its occurrence on the leading
or lagging strand of the replication fork when the direction of replication is
known. In all cases in which the orientation of the asymmetry could be determined
with respect to DNA replication, the products were consistent with a preference
for deletion on the lagging strand of the fork. The data include replication
slippage in three situations: on the chromosome of E. coli, in bacteriophage
lambda and in high-copy-number pUC-based plasmids.
PMID- 9643541
TI - Schizosaccharomyces pombe isp4 encodes a transporter representing a novel family
of oligopeptide transporters.
AB - We have recently cloned an oligopeptide transport gene from Candida albicans
denoted OPT1. This gene showed significant sequence similarity to three open
reading frames (ORFs) with no previously established function: isp4 from
Schizosaccharomyces pombe and Saccharomyces cerevisiae YJL212C and YPR194C,
identified during the genome project. The S. pombe gene isp4 was originally
identified by Sato et al. as a gene that was upregulated through nitrogen
starvation induction of meiosis. However, an isp4delta strain exhibited a wild
type phenotype with respect to sexual differentiation. We have found that the
same isp4delta strain is deficient in tetrapeptide transport activity as measured
by its resistance to toxic tetrapeptides, by its inability to accumulate a
radiolabelled tetrapeptide and by the inability to use tetrapeptides as a sole
source of an amino acid to satisfy an auxotrophic requirement. Similarly, we
found that the ORF YPR194C from S. cerevisiae encodes an oligopeptide
transporter. Sequence analyses as well as physiological evidence has led us to
propose that the proteins encoded by isp4 and the genes identified from S.
cerevisiae and C. albicans comprise a new group of transporters specific for
small oligopeptides, which we have named the OPT family.
PMID- 9643542
TI - Involvement of two A-factor receptor homologues in Streptomyces coelicolor A3(2)
in the regulation of secondary metabolism and morphogenesis.
AB - Nucleotide sequences homologous to arpA encoding the A-factor receptor protein
(ArpA) of Streptomyces griseus are distributed in a wide variety of
streptomycetes. Two genes, cprA and cprB, each encoding an ArpA-like protein were
found and cloned from Streptomyces coelicolor A3(2). CprA and CprB shared 90.7%
identity in amino acid sequence and both showed about 35% identity to ArpA.
Disruption of cprA by use of an M13 phage-derived single-stranded vector resulted
in severe reduction of actinorhodin and undecylprodigiosin production. In
addition, the timing of sporulation in the cprA disruptants was delayed by 1 day.
The cprA gene thus appeared to act as a positive regulator or an accelerator for
secondary metabolite formation and sporulation. Consistent with this idea,
introduction of cprA on a low-copy-number plasmid into the parental strain led to
overproduction of these secondary metabolites and accelerated the timing of
sporulation. On the other hand, cprB disruption resulted in precocious and
overproduction of actinorhodin. However, almost no effect on undecylprodigiosin
was detected in the cprB disruptants. Sporulation of the cprB disruptant began 1
day earlier than the parental strain. The cprB gene thus behaved as a negative
regulator on actinorhodin production and sporulation. Consistent with this, extra
copies of cprB in the parental strain caused reduced production of actinorhodin
and delay in sporulation. It is thus concluded that both cprA and cprB play
regulatory roles in both secondary metabolism and morphogenesis in S. coelicolor
A3(2), just as the arpA/A-factor system in Streptomyces griseus.
PMID- 9643543
TI - Inducer exclusion by glucose 6-phosphate in Escherichia coli.
AB - The main mechanism causing catabolite repression by glucose and other carbon
sources transported by the phosphotransferase system (PTS) in Escherichia coli
involves dephosphorylation of enzyme IIA(Glc) as a result of transport and
phosphorylation of PTS carbohydrates. Dephosphorylation of enzyme IIA(Glc) leads
to 'inducer exclusion': inhibition of transport of a number of non-PTS carbon
sources (e.g. lactose, glycerol), and reduced adenylate cyclase activity. In this
paper, we show that the non-PTS carbon source glucose 6-phosphate can also cause
inducer exclusion. Glucose 6-phosphate was shown to cause inhibition of transport
of lactose and the non-metabolizable lactose analogue methyl-beta-D
thiogalactoside (TMG). Inhibition was absent in mutants that lacked enzyme
IIA(Glc) or were insensitive to inducer exclusion because enzyme IIA(Glc) could
not bind to the lactose carrier. Furthermore, we showed that glucose 6-phosphate
caused dephosphorylation of enzyme IIA(Glc). In a mutant insensitive to enzyme
IIA(Glc)-mediated inducer exclusion, catabolite repression by glucose 6-phosphate
in lactose-induced cells was much weaker than that in the wild-type strain,
showing that inducer exclusion is the most important mechanism contributing to
catabolite repression in lactose-induced cells. We discuss an expanded model of
enzyme IIA(Glc)-mediated catabolite repression which embodies repression by non
PTS carbon sources.
PMID- 9643544
TI - Intramolecular synergism in an engineered exo-endo-1,4-beta-glucanase fusion
protein.
AB - Exoglucanase CelY and endoglucanase CelZ from the cellulolytic thermophile
Clostridium stercorarium act in synergism to hydrolyse cellulosic substrates. To
increase the efficiency of the hydrolytic degradation process, an artificial
multienzyme carrying both enzymatic activities on one polypeptide chain was
constructed by gene fusion. A segment of CelZ, CelZdeltaBB'C (designated CelZC'),
comprising the catalytic domain and the adjacent domain C' homologous to the
cellulose-binding domain family IIIc, was fused to the C-terminus of CelY,
yielding the fusion protein CelY-CelZC', designated CelYZ. The large fusion
protein (170 kDa) could be isolated from a recombinant Escherichia coli strain in
its intact form retaining the pronounced thermostability of the fusion partners.
As a true multienzmye, CelYZ exhibited both exoglucanase and endoglucanase
activities. The cellulolytic activity of the fusion protein was three- to
fourfold higher than the sum of the individual activities. Dilution experiments
showed that the enhanced cellulolytic activity of the multienzyme resulted from
intramolecular synergism of the fusion partners. The product profiles and the
kinetic constants of cellulose hydrolysis support a new mechanistic model
proposed for explaining the co-operativity of the two catalytic domains within
the multienzmye.
PMID- 9643545
TI - Antisense inhibition of expression of cysteine proteinases does not affect
Entamoeba histolytica cytopathic or haemolytic activity but inhibits
phagocytosis.
AB - Inhibition of most of the expression of the cysteine proteinases of Entamoeba
histolytica strain HM-1:IMSS was successfully performed by transcription of ehcp5
antisense RNA using the promoter of ehg34, which encodes a L21 ribosomal protein
of E. histolytica. We have generated a stable transfectant in which the overall
level of cysteine proteinase activity is strongly reduced ( 90%). This
transfectant has a normal growth rate in Diamond's TYI-S-33 medium, a cytopathic
and haemolytic activity similar to the control HM-1:IMSS pEhAct-Neo transfectant
but with a significantly lower phagocytic activity.
PMID- 9643546
TI - Stress induction of the Bacillus subtilis clpP gene encoding a homologue of the
proteolytic component of the Clp protease and the involvement of ClpP and ClpX in
stress tolerance.
AB - The Bacillus subtilis clpP gene, encoding the proteolytic component of the Clp or
Ti protease, was cloned and sequenced. The amount of clpP-specific mRNA increased
after heat shock, salt and ethanol stress, as well as after treatment with
puromycin. Two transcriptional start sites upstream of the clpP structural gene
were identified, preceded by sequences resembling the consensus sequences of
promoters recognized by sigmaA and sigmaB transcriptional factors of the B.
subtilis RNA polymerase respectively. Transcription initiation occurred
predominantly at the putative sigmaA-dependent promoter in exponentially growing
cells and was induced under stress conditions. After exposure to stress,
initiation of transcription also increased at the sigmaB-dependent promoter, but
to a lesser extent, indicating that clpP belongs to a double promoter-controlled
subgroup of class III general stress genes in B. subtilis. In a sigB mutant
strain, clpP remained heat and stress inducible at the sigmaA-dependent promoter.
BgaB-reporter gene fusions, carrying either the sigmaA- or the sigmaB-dependent
promoter, showed a higher bgaB induction at the sigmaA-dependent promoter,
whereas a significantly lower level of induction was measured at the sigmaB
dependent promoter. The sigmaA-dependent promoter appeared to be crucial for the
heat-inducible transcription of clpP. A CIRCE (controlling inverted repeat of
chaperone expression) element, the characteristic regulation target of class I
heat shock genes such as dnaK and groESL, was not found between the
transcriptional and translational start sites. Mutants lacking either the
proteolytic component ClpP or the regulatory ATPase component ClpX were
phenotypically distinct from the wild type. Both mutants produced chains of
elongated cells and exhibited severely impaired growth under stress conditions
and starvation. Comparison of two-dimensional protein gels from wild-type cells
with those from clpP and clpX mutant cells revealed several changes in the
protein pattern. Several proteins, such as GroEL, PpiB, PykA, SucD, YhfP, YqkF,
YugJ and YvyD, which were found preferentially in higher amounts in both clpP and
clpX mutants, might be potential substrates for the ClpXP protease.
PMID- 9643547
TI - Polypeptide binding of Escherichia coli FtsH (HflB).
AB - The Escherichia coli FtsH protein is a membrane-bound and ATP-dependent protease.
In this study, we describe ATP-dependent conformational changes in FtsH as well
as a polypeptide binding ability of this protein. A 33 kDa segment of FtsH became
trypsin resistant in the presence of ATP. ATP and ATPgammaS prevented self
aggregation of detergent-solubilized FtsH-His6-Myc at 37 degrees C, again
suggesting that the binding of ATP induces a conformational change in FtsH.
Affinity chromatography showed that FtsH-His6-Myc can associate with denatured
alkaline phosphatase (PhoA) but not with the native enzyme. Denatured PhoA also
prevented the aggregation of FtsH, and these two proteins co-sedimented through a
sucrose gradient. Binding between FtsH-His6-Myc and detergent-solubilized SecY
was also demonstrated. Although FtsH-bound SecY was processed further for ATP
dependent proteolysis, FtsH-bound PhoA was not. Thus, FtsH association with
denatured PhoA is uncoupled from proteolysis. Overproduction of FtsH
significantly increased the cytoplasmic localization of the PhoA moiety of a MalF
PhoA hybrid protein, in which a charged residue had been introduced into a
transmembrane segment. Thus, denatured PhoA binding of FtsH may also occur in
vivo.
PMID- 9643548
TI - Targeted deletion and mutational analysis of the essential (2Fe-2S) plant-like
ferredoxin in Synechocystis PCC6803 by plasmid shuffling.
AB - The genes encoding (2Fe-2S) plant-like ferredoxins were studied in the widely
used cyanobacterium Synechocystis PCC6803. The fedl gene (ssI0020) coding for the
most abundant ferredoxin product was found to be expressed strongly as a light
induced monocistronic transcript, whereas the other fed genes appeared to be
silent (sIr1828) or moderately expressed as polycistronic transcripts regulated
by either light fluence (sIr0150, negative control) or glucose availability
(sII1382). fedl was found to be critical to Synechocystis PCC6803 viability in
spite of sIr0150, sII1382 or flavodoxin induction, even after the addition of
glucose that compensates for the loss of photosynthesis. Nevertheless, fedl could
be deleted from all chromosome copies in cells propagating a fedl gene (even of
heterologous origin) on a replicating plasmid. This strain was used as the host
for the subsequent introduction of fedl mutant alleles propagated on a second
vector. Analysis of the fedl mutant strains generated after plasmid exchange
showed that the C18-C85 disulphide bridge is not central either to the tight
compaction of ferredoxin I or to its reduction by photosystem I and demonstrated
that the length of the Fedl carboxy terminus is important for effective PSI/FedI
interactions. The plasmid-shuffling strategy presently described has general
applicability for mutational analysis of essential genes in many organisms, as it
is based on promiscuous plasmids.
PMID- 9643549
TI - Lactococcus lactis phage operon coding for an endonuclease homologous to RuvC.
AB - The function of the Lactococcus lactis bacteriophage bIL66 middle time-expressed
operon (M-operon), involved in sensitivity to the abortive infection mechanism
AbiD1, was examined. Expression of the M-operon is detrimental to Escherichia
coli cells, induces the SOS response and is lethal to recA and recBC E. coli
mutants, which are both deficient in recombinational repair of chromosomal double
stranded breaks (DSBs). The use of an inducible expression system allowed us to
demonstrate that the M-operon-encoded proteins generate a limited number of
randomly distributed chromosomal DSBs that are substrates for ExoV-mediated DNA
degradation. DSBs were also shown to occur upstream of the replication initiation
point of unidirectionally theta-replicating plasmids. The characteristics of the
DSBs lead us to propose that the endonucleolytic activity of the M-operon is not
specific to DNA sequence, but rather to branched DNA structures. Genetic and
physical analysis performed with different derivatives of the M-operon indicated
that two orfs (orf2 and orf3) are needed for nucleolytic activity. The orf3
product has amino acid homology with the E. coli RuvC Holliday junction
resolvase. By site-specific mutagenesis, we have shown that one of the amino acid
residues constituting the active centre of RuvC enzyme (Glu-66) and conserved in
ORF3 (Glu-67) is essential for the nucleolytic activity of the M-operon gene
product(s). We therefore propose that orf2 and orf3 of the M-operon code for a
structure-specific endonuclease (M-nuclease), which might be essential for phage
multiplication.
PMID- 9643550
TI - Viral escape from antisense RNA.
AB - RNA coliphage SP was propagated for several generations on a host expressing an
inhibitory antisense RNA complementary to bases 31-270 of the positive-stranded
genome. Phages evolved that escaped inhibition. Typically, these escape mutants
contained 3-4 base substitutions, but different sequences were observed among
different isolates. The mutations were located within three different types of
structural features within the predicted secondary structure of SP genomic RNA:
(i) hairpin loops; (ii) hairpin stems; and (iii) the 5' region of the phage
genome complementary to the antisense molecule. Computer modelling of the mutant
genomic RNAs showed that all of the substitutions within hairpin stems improved
the Watson-Crick pairing of the stem. No major structural rearrangements were
predicted for any of the mutant genomes, and most substitutions in coding regions
did not alter the amino acid sequence. Although the evolved phage populations
were polymorphic for substitutions, many substitutions appeared independently in
two selected lines. The creation of a new, perfect, antisense RNA against an
escape mutant resulted in the inhibition of that mutant but not of other escape
mutants nor of the ancestral, unevolved phage. Thus, at least in this system, a
population of viruses that evolved to escape from a single antisense RNA would
require a cocktail of several antisense RNAs for inhibition.
PMID- 9643551
TI - Domain structure and RNA annealing activity of the Escherichia coli regulatory
protein StpA.
AB - The Escherichia coli regulatory protein StpA bears striking similarity to the
chromatin-associated protein H-NS. These two proteins have many structural,
functional and mechanistic parallels. Although H-NS is more abundant in the cell,
both proteins act as transcriptional regulators, both bind to curved DNA and both
restrain DNA supercoils. However, StpA is better able to promote RNA annealing
and trans-splicing in vitro. In this study, phylogenetic analyses and experiments
to examine the protease sensitivity of StpA and H-NS suggest a similar structure
for the two proteins. Both proteins consist of two structured domains separated
by an exposed protease-sensitive linker. The N-terminal (StpA-NterL) and C
terminal (StpA-CterL) domains of StpA, as well as the full-length StpA and H-NS
proteins, were cloned, overproduced in E. coli and purified to homogeneity. StpA
CterL, but not StpA-NterL, promotes strand annealing of complementary RNA
oligonucleotides and in vitro trans-splicing of a model group I intron. Both StpA
and StpA-CterL exhibited stronger RNA-modulating activity than H-NS. Phylogenetic
analyses showed that the N-terminal and C-terminal domains can exist
autonomously. The phylogenetic and experimental data are compatible with a two
domain model for StpA and H-NS, with independently functioning modules joined by
a non-conserved linker, and with the observed RNA-related activities residing
entirely within the C-terminal domain.
PMID- 9643552
TI - Supracriticality and the prion.
PMID- 9643553
TI - Type III secretion in Chlamydia: a case of deja vu?
PMID- 9643554
TI - Neural mechanisms underlying stereoscopic vision.
AB - The progressive frontalization of both eyes in mammals causes overlap of the left
and right visual fields, having as a consequence a region of binocular field with
single vision and stereopsis. The horizontal separation of the eyes makes the
retinal images of the objects lying in this binocular field have slight
horizontal and vertical differences, termed disparities. Horizontal disparities
are the main cue for stereopsis. In the past decades numerous physiological
studies made on monkeys, which have in many aspects a similar visual system to
humans, showed that a population of visual cells are capable of encoding the
amplitude and sign of horizontal disparity. Such disparity detectors were found
in cortical visual areas V1, V2, V3, V3A, VP, MT (V5) and MST of monkeys and in
the superior colliculus of the cat and opossum. According to their disparity
tuning function, these cells were first grouped into tuned excitatory, tuned
inhibitory, near and far sub-groups. Subsequent studies added two more
categories, tuned near and tuned far cells. Asymmetries between left and right
receptive field position, on and off regions, and intra-receptive field wiring
are believed to be the neural mechanisms of disparity detection. Because
horizontal disparity alone is insufficient to compute reliable stereopsis,
additional information about fixation distance and angle of gaze is required.
Thus, while there is unequivocal evidence of cells capable of detecting
horizontal disparities, it is not known how horizontal disparity is calibrated.
Sensitivity to vertical disparity and information about the vergence angle or eye
position may be the source of this additional information.
PMID- 9643555
TI - Head direction cells and the neurophysiological basis for a sense of direction.
AB - Animals require two types of fundamental information for accurate navigation:
location and directional heading. Current theories hypothesize that animals
maintain a neural representation, or cognitive map, of external space in the
brain. Whereas cells in the rat hippocampus and parahippocampal regions encode
information about location, a second type of allocentric spatial cell encodes
information about the animal's directional heading, independent of the animal's
on-going behaviors. These head direction (HD) cells are found in several areas of
the classic Papez circuit. This review focuses on experimental studies conducted
on HD cells and describes their discharge properties, functional significance,
role in path integration, and responses to different environmental manipulations.
The anterior dorsal thalamic nucleus appears critical for the generation of the
directional signal. Both motor and vestibular cues also play important roles in
the signal's processing. The neural network models proposed to account for HD
cell firing are compared with known empirical findings. Examples from clinical
cases of patients with topographical disorientation are also discussed. It is
concluded that studying the neural mechanisms underlying the HD signal provides
an excellent opportunity for understanding how the mammalian nervous system
processes a high level cognitive signal.
PMID- 9643556
TI - Cortical pathways to the mammalian amygdala.
AB - The amygdaloid nuclear complex is critical for producing appropriate emotional
and behavioral responses to biologically relevant sensory stimuli. It constitutes
an essential link between sensory and limbic areas of the cerebral cortex and
subcortical brain regions, such as the hypothalamus, brainstem, and striatum,
that are responsible for eliciting emotional and motivational responses. This
review summarizes the anatomy and physiology of the cortical pathways to the
amygdala in the rat, cat and monkey. Although the basic anatomy of these systems
in the cat and monkey was largely delineated in studies conducted during the
1970s and 1980s, detailed information regarding the cortico-amygdalar pathways in
the rat was only obtained in the past several years. The purpose of this review
is to describe the results of recent studies in the rat and to compare the
organization of cortico-amygdalar projections in this species with that seen in
the cat and monkey. In all three species visual, auditory, and somatosensory
information is transmitted to the amygdala by a series of modality-specific
cortico-cortical pathways ("cascades") that originate in the primary sensory
cortices and flow toward higher order association areas. The cortical areas in
the more distal portions of these cascades have stronger and more extensive
projections to the amygdala than the more proximal areas. In all three species
olfactory and gustatory/visceral information has access to the amygdala at an
earlier stage of cortical processing than visual, auditory and somatosensory
information. There are also important polysensory cortical inputs to the
mammalian amygdala from the prefrontal and hippocampal regions. Whereas the
overall organization of cortical pathways is basically similar in all mammalian
species, there is anatomical evidence which suggests that there are important
differences in the extent of convergence of cortical projections in the primate
versus the nonprimate amygdala.
PMID- 9643557
TI - The regulation and biological activity of interleukin 12.
AB - Interleukin 12 (IL-12) is a pleiotropic cytokine and mediates several biological
activities on human T and natural killer (NK) cells, including induction of IFN
gamma production, enhancement of cell-mediated cytotoxicity and comitogenic
effects on resting T-cells. The major cellular sources producing IL-12 are
antigen-stimulated monocytes, macrophages, and B-cells isolated from peripheral
blood mononuclear cells (PBMC). Our laboratory has investigated the regulation of
IL-12 gene expression in both cord blood and adult PBMC, and the effects of IL-12
on induction of IFN-gamma production, NK, and lymphokine-activated killer (LAK)
cytotoxicity. IL-12 mRNA expression and protein production in LPS-stimulated cord
blood MNC were 3-4 fold decreased when compared with adult PBMC. There were no
differences between cord blood and adult PBMC in both basal levels of
transcription or the degree of transcriptional activation of the IL-12 gene.
Additionally, the half-life of IL-12 p40 mRNA was 3-fold lower in activated cord
blood compared to adult PBMC. Exogenous IL-12 induced a significant increase of
IFN-gamma from both cord and adult PBMC. Cord MNC has significantly reduced
levels of NK activity, and IL-12 significantly enhanced cord blood NK
cytotoxicity up to similar levels in adult PBMC. IL-12 also significantly
enhanced cord blood NK and LAK activities against a broad range of neuroblastoma,
leukemia, and lymphoma cell lines. Lower doses of IL-12 and IL-15 concomitantly
generated either synergistic or additive effects on cord blood NK and LAK
cytotoxicities. In light of the important biological functions of IL-12, reduced
expression and production of IL-12 from activated cord blood may contribute to
the immaturity of cord blood cellular immunity and contribute, in part, to
decreased severe graft vs. host disease following unrelated cord blood stem cell
transplantation. IL-12 enhancement of IFN-gamma, NK, and LAK activity in
activated cord blood MNC up to comparable levels in adult PBMC suggests that
exogenous IL-12 stimulation can compensate for the immaturity in cord blood
cellular immunity. These characteristics of IL-12 biological activity strongly
suggest its potential usefulness in future cancer immunotherapy.
PMID- 9643558
TI - Enhancement of adenovirus-mediated gene transfer to human bone marrow cells.
AB - Adenovirus infection of CD34+ hematopoietic stem/progenitor cells is dependent on
the multiplicity of infection (MOI), time of incubation, the volume in which the
co-incubation occurs and the presence or absence of growth factors. Studies
revealed that a brief co-incubation (1-8 hours), resulted in low levels of
transgene expression, suggesting that adenovirus infection of CD34+ cells occurs
slowly, and optimal transduction requires a 24 hour exposure to adenovirus.
Infection by Ad/beta-gal or Ad/p53 at a MOI of 500:1 provided a high transduction
efficiency but inhibited hematopoietic function. However, treatment at a MOI of
50-100 resulted in efficient transduction (10.7-15.7% positive) without
detectable toxicity. Secondary proof of adenovirus transgene expression was
demonstrated by detection of mRNA for p53 in Ad/p53 infected stem cells. We
conclude that a 24 hour exposure to recombinant adenovirus encoding p53 or beta
gal, at a MOI of 50-100 is optimal for in vitro gene transfer to BM cells and has
no significant effect on hematopoietic function. Adenovirus-mediated transduction
of BM cells can also be modulated by growth factors (IL-3, GM-CSF and G-CSF) with
improved gene delivery and maintenance of hematopoietic function. In summary,
adenovirus vectors can be used to transiently transduce stem cells, and
conditions have been defined to maximize expression and limit inhibitory effects
on CD34+ cells. These data support continued investigation of this vector for
local cytokine delivery and purging of stem cell products.
PMID- 9643559
TI - Antitumor agent-induced apoptosis in myeloid leukemia cells: a controlled
suicide.
AB - Traditional antitumor research has generally believed that the cytotoxicity of
antitumor agents was directly correlated with the amount of drug-induced cellular
lesions. Accordingly, oncologists have tried to improve anticancer agent/target
interactions by increasing the intracellular dose of active effectors. However, a
growing body of evidence stemming from both clinical and experimental
observations, strongly suggests that similar anticancer-induced lesions may
result in different cellular responses, greatly influencing cytotoxicity. For
example, it has been shown that in some but not all cellular models, antitumor
agents trigger apoptosis, an irreversible process which leads to a rapid and
complete elimination of tumor cells. Several of these studies also demonstrated
that apoptosis induced by antitumor agents is highly regulated by multiple
signaling pathways which are themselves influenced by oncogenes, protein kinase
activities, external stimuli and the oxidative balance. Therefore, it appears
that cell death commitment is controlled by both external and internal factors
which interfere downstream of drug- or ionizing radiation-target interaction. The
characterization of these mediators may provide novel strategies for modulating
intracellular signaling pathways in order to promote apoptosis in drug-resistant
tumor cells.
PMID- 9643560
TI - Growth control mechanisms in multiple myeloma.
AB - Interleukin-6 (IL-6) is the major growth factor for the malignant plasma cell
clone in patients with multiple myeloma (MM). Although interferon-alpha (IFN
alpha) has been widely used as maintenance therapy in MM, controversy exists as
to its clinical utility. This review summarizes data showing that cell growth
arrest brought about by type I (IFNs-alpha/beta) and type II (IFN-gamma) IFNs
occurs in part through utilization/modification of various components of the
otherwise stimulatory Jak-STAT and Ras signaling pathways triggered by IL-6.
Recent experimental results indicating that IFN-alpha acts as a survival factor
for certain myeloma cell lines and frequently induces endogenous IL-6 expression
may help to explain the conflicting clinical findings obtained in this
heterogeneous disease with this usually potent growth inhibitor. By comparison,
consistent antiproliferative activity exhibited by IFN-gamma on IL-6-dependent
myeloma cell lines and primary myeloma cells from patients suggests that further
investigation of the possible value of this cytokine in the treatment of MM may
be warranted.
PMID- 9643561
TI - Developmental aspects of dendritic cells in vitro and in vivo.
AB - Dendritic cells (DC) are potent antigen presenting cells that possess the unique
ability to stimulate naive T-cells. By studying DC derived from various tissues
it has been shown that the morphology, phenotype and function of DC alter as they
undergo a complex process of maturation. DC are derived from bone marrow
progenitors and circulate in the blood as immature precursors prior to migration
into the peripheral tissues. Within tissues DC are specialised in the taking up
and processing of antigen so that it may be presented on MHC class II molecules.
Upon appropriate stimulation tissue DC undergo further maturation and migrate to
secondary lymphoid tissue where they present antigen to T-cells and induce an
immune response. Studies of DC maturation in vitro have defined the cytokines
regulating their development from CD34+ myelomonocytic progenitors as well as
from more mature peripheral blood precursors. An alternative pathway of
differentiation from thymic precursors has also been described. As a result of
these studies, DC may now be generated and manipulated ex-vivo for clinical
applications in oncology, autoimmune disease and transplantation.
PMID- 9643562
TI - EBV-NK cells interactions and lymphoproliferative disorders.
AB - Epstein-Barr virus (EBV) usually infects epithelial cells in the oropharynx and B
lymphocytes asymptomatically. Occasionally, however, EBV infects T-cells and
natural killer (NK) cells, and infection of these cells has been associated with
the development of leukemias and lymphomas. EBV-positive lymphoproliferative
disorders of NK cells have been reported with increasing frequency, but the
interactions between EBV and NK cells are not fully understood, in part because
NK cells are not usually infected with EBV in vitro. The lymphoma-derived EBV
positive NK cell line, YT, has been useful in the study of EBV infection of NK
cells. YT cells express the EBV-associated nuclear antigen (EBNA)-1, the latent
membrane protein (LMP)-1, and LMP-2A, but not EBNA-2 and LMP-2B genes. This
pattern of latent gene expression is compatible with a type II latency program,
normally associated with nasopharyngeal carcinoma, Hodgkin's disease, and T-cell
lymphoma. In this report, we summarize recent information on EBV-NK cell
interactions and EBV-positive lymphoproliferative disorders of NK cells.
PMID- 9643563
TI - Parathyroid hormone-related protein in hypercalcemia associated with
hematological malignancy.
AB - Hypercalcemia is an important complication in multiple myeloma as well as T-cell
leukemia/lymphoma, and is moderately common in high and intermediate grade non
Hodgkin's lymphoma. The underlying mechanism has been unclear because the
neoplastic cells are usually present in the bone marrow, where they are in a
position to produce short range effects on bone resorption which are difficult to
identify. This contrasts with the situation in hypercalcemia associated with non
metastatic carcinoma, where it has been clearly demonstrated that the most common
cause is release from the tumor of a humoral mediator, Parathyroid Hormone
related Protein (PTHrP). Roles have been advocated in multiple myeloma for
release of a number of other cytokines with osteolytic capacity on the basis of
their enhancement of osteolytic activity in cultured fetal rat bone, although a
causal relationship in patients has not been established. PTHrP has more recently
been implicated in the genesis of hypercalcemia in patients with hematological
malignancies by the demonstration in a proportion of cases of increased
circulating levels of PTHrP, comparable to those in hypercalcemia due to cancer.
Immunohistochemical studies indicate neoplastic hemopoietic cells can contain
PTHrP, and thus have the capacity to act in a paracrine manner to enhance local
bone resorption and contribute to the development of hypercalcemia.
PMID- 9643564
TI - Genomic DNA amplification and the detection of t(2;5)(p23;q35) in lymphoid
neoplasms.
AB - Anaplastic large cell lymphoma (ALCL) is an intermediate grade Non-Hodgkin's
lymphoma (NHL) characterized by the frequent presence of the t(2;5)(p23;q35).
This translocation fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a
protein kinase gene (Anaplastic Lymphoma Kinase, ALK) on chromosome 2p23. In
order to determine the frequency of t(2;5) we used a DNA polymerase chain
reaction (PCR) amplification using genomic DNA, 5'-primers derived from the NPM
gene, and 3'-primers derived from the ALK gene. The presence of amplifiable DNA
in the samples was established with PCR and oligonucleotide primers designed to
amplify a 3,016 bp fragment from the beta-globin locus. The t(2;5) PCR assay was
established using DNA isolated from three t(2;5)-positive ALCL cell lines. Its
ability to amplify genomic DNA prepared for routine molecular diagnostic use was
validated using archival DNA from four ALCL tumors known to be t(2;5)-positive.
Its sensitivity was established by serially diluting t(2;5)-positive DNA in
normal DNA: amplicons were generated in 100% of reactions diluted 10(4)-fold (6-8
cells per tube) and in 30% of those diluted 10(5)-fold (0.6-0.8 cells per tube.)
We subsequently analyzed archival genomic DNA extracted from 38 ALCL, 77 NHLs, 37
Hodgkin's lymphomas, and 9 lymphomatoid papuloses. The t(2;5) was detected in 6
ALCLs (16%, 95% confidence intervals 6%-31%), but not in any other lymphoma, or
in lymphomatoid papulosis. By using the published sequence of the fourth NPM
intron that is involved in t(2;5) and by sequencing the individual tumor
amplicons and also the normal ALK intron that is involved in t(2;5), we
established that all breakpoints involve the same introns in the ALK and NPM
loci. Detailed analysis demonstrated that each translocation generates a unique
breakpoint sequence, and suggested that sequence homology between the ALK and NPM
intron sequences may be involved in the translocation. We conclude that genomic
DNA-PCR is useful for the detection of t(2;5) that in our patient population is
restricted to ALCL and is not detectable in other NHL, Hodgkin's disease, or
lymphomatoid papulosis. More work is needed to determine the prognostic
significance of t(2;5), and to establish the utility of the genomic DNA PCR in
monitoring minimal residual disease.
PMID- 9643565
TI - Bone marrow involvement in lymphoma: the importance of marrow magnetic resonance
imaging.
AB - Detection of bone marrow involvement is important for staging and treatment
decisions in patients with lymphoma. Although routine bone marrow evaluation is
based on aspirates and bone marrow biopsies, new diagnostic tools are required to
improve diagnostic accuracy. Visual and quantitative assessment of the bone
marrow by magnetic resonance (MR) imaging is useful for the detection of occult
lymphomatous marrow involvement. MRI is also suitable for the evaluation of
disease extent in the bone marrow. Furthermore, abnormal images on marrow MRI may
be associated with a significantly poorer survival in patients with lymphoma,
regardless of histologic findings in the marrow. Evaluation of the bone marrow by
MRI is essential to assess disease status in patients with lymphoma.
PMID- 9643566
TI - Dyshematopoiesis in de novo acute myeloid leukemia: cell biological features and
prognostic significance.
AB - Dyshematopoiesis was found in 44 (42.3%) of 104 cases of de novo acute myeloid
leukemia (AML). Dyshematopoietic AML (dys-AML) and AML without hematopoietic
dysplasia (non-dys-AML) were compared with regard to biological, hematological,
immunophenotypic, and cytogenetic parameters as well as prognostic criteria.
Median age of patients was 55 years in both groups. In dys-AML, the median
leukocyte count (p = 0.04), peripheral blast (p = 0.02) and medullary blast cell
count (p < 0.001) were significantly decreased, whereas the median platelet count
(p - 0.04) was increased. Immunophenotyping demonstrated that leukemic blast
cells in dys-AML more frequently expressed the adhesion molcules CD54 (p = 0.05)
and CD58 (p = 0.08) than leukemic cells in non-dys-AML. Cytogenetically, we
distinguished two karyotypic patterns, one group with a normal karyotype or
prognostically favorable single chromosome aberrations ("P(0)-karyotype"), and
another one with unfavorable single aberrations or complex aberrations ("P(1)
karyotype"). The incidence of these groups was not significantly different
between dys-AML and non-dys-AML. Complete remission rate (CRR) after induction
chemotherapy (p = 0.03) and overall survival time (OS; p = 0.03) were
significantly lower in dys-AML. In addition, median disease free survival (DFS; p
= n.s.) was inferior compared to non-dys-AML. In the dys-AML as well as in the
non-dys-AML patient group, CRR, DFS, and OS were decreased in the P(1)-compared
to the P(0)-subgroup. We conclude that dyshematopoietic AML is characterized by
specific cell biological features and that hematopoietic and cytogenetic status
represent complementary prognostic factors in de novo AML.
PMID- 9643567
TI - Changes in the functional capacity of marrow stromal cells after autologous bone
marrow transplantation.
AB - Marrow stromal cells were evaluated several months after autologous BMT for their
capacity to support both normal hemopoiesis and secrete the main growth factors
involved in its control, G-CSF, GM-CSF, IL-3 and SCF. Stromal layers (SL) were
obtained by long-term marrow cultures (LTMC) established from 15 patients (9 with
hematologic malignancies and 6 with solid tumors) 3 months after autologous BMT
and were compared to pre-graft patients. After irradiation, both post-graft and
pre-graft SL were recharged with the same inoculum of normal marrow cells. As
compared to pre-graft values, CFU-GM production on post-graft SL was
significantly increased during the first 2 weeks of culture whereas it was
decreased from week 3 to week 8. These findings were only observed in patients
with hematologic malignancies and not in patients with solid tumors. Growth
factor secretion was evaluated by ELISA in the supernatants of unstimulated and
IL-1-stimulated SL from 10 post-graft patients, 13 pre-graft patients and 5
normal controls. In any group of patients, IL-3 was undetectable either
spontaneously or after IL-1-stimulation. As compared to controls, secretion by IL
1-stimulated SL was not different for GM-CSF in pre- and post-graft patients but
tended to be decreased for G-CSF in post-graft patients. SCF secretion, which was
not induced by IL-1, appeared dramatically decreased in both pre- and post-graft
patients. The capacity of post-graft SL to support CFU-GM growth in LTMC was
correlated at week 1 with G-CSF secretion and from week 3 to week 8 with SCF
secretion. These results suggest that microenvironment remains qualitatively
damaged several months after BMT involving a decreased capacity both to support
early hemopoiesis and to secrete SCF, particularly in patients grafted for
hemopoietic malignancies.
PMID- 9643568
TI - Expression of lung resistance protein and correlation with other drug resistance
proteins and outcome in myelodysplastic syndromes.
AB - The major vault lung resistance protein LRP is a cytoplasmic protein involved in
drug resistance, especially in acute myeloid leukemia. We looked for LRP
overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on
marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP
overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of
marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results
between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66%
of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+)
in 33% of the cases. No correlation was seen between LRP overexpression and FAB
type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts.
Furthermore, in the 18 cases treated with anthracycline-AraC intensive
chemotherapy and the 7 cases treated with low dose AraC, the response rate was
not significantly different in LRP+ and LRP- patients. Survival was also similar
in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more
frequent in MDS than in de novo AML and, as in AML, is only partially correlated
with PGP expression. In our experience, however, LRP was not a prognostic factor
for response to chemotherapy and survival in MDS.
PMID- 9643570
TI - Segmental jumping translocation in leukemia and lymphoma with a highly complex
karyotype.
AB - In order to identify the oncogene associated with malignant transformation 141
leukemia and malignant lymphoma patients were studied by FISH. Specific
chromosome regions were translocated onto structurally abnormal chromosomes,
resulting in partial tri-, tetra-, or pentasomy of these regions. We designated
this type of chromosomal translocation as a "segmental jumping translocation
(SJT)". These SJTs were found in several chromosomal regions such as 8q24, 9q34,
11q13, 11q23, 13q14, 14q24-q32, 21q22 and 22q11. The SJT at 9q34, which involved
the ABL oncogene, was found in three of nine secondary leukemia patients who were
treated with anticancer drugs and radiation. Non-Hodgkin's lymphoma and acute
myeloid leukemia (AML) patients had 3-7 copies of SJT at 11q13 or 11q23. SJT at
14q32 and 21q22 were predominantly detected in the acute type of adult T-cell
leukemia (8 of 27 patients) and in AML (5 of 17 patients). The size of the SJT
regions varied among the patients. The overlapping region within the SJT could
involve oncogene(s) associated with transformation to the advanced stage in
leukemia and lymphoma patients. The SJT provides evidence of a new mechanism for
gene amplification and formation of unidentified marker chromosomes in the
advanced disease stage.
PMID- 9643569
TI - Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or
AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in
bone marrow.
AB - Here we studied minimal residual disease (MRD) of patients with acute myeloid
leukemia (AML) who have PML/RAR alpha or AML1/ETO as well as the phenotypic
analysis of lymphocyte subsets involved in antitumor immunity. Eight patients in
long-term (LT; 3 to 15 years) and 15 patients in short-term (ST; up to 3 years)
remission were studied. Using the reverse transcription-polymerase chain reaction
(RT) assay, the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha
transcript and 10(-4) to 10(-5) for the AML1/ETO transcript. Simultaneously, T
lymphocyte subsets and NK cells from the peripheral blood (PB) and bone marrow
(BM) were investigated by flow cytometric analysis. Four of the eight patients in
LT and 7 of the 15 patients in ST remission were MRD-positive. Although all MRD
positive patients in LT remission are still until now event-free, 3 of the 7 MRD
positive (MRD+) patients in ST remission soon relapsed. The total populations of
CD4+, CD8+ and CD56+ [possible T-cell and natural killer (T/NK) populations] in
the BM of ST patients and MRD+/LT patients were significantly (p < .01) low. The
CD8+ CD28+ population showed the same tendency (p < .01-.02). The T/NK subsets in
the BM of MRD-negative (MRD-) LT (MRD-/LT) patients showed similar numbers of
cells as normal volunteers. Basically, the total percentage of the CD4+, CD8+ and
CD56+ cell populations in the BM was increased and in the following order: MRD
/LT patients, normal volunteers, MRD+/LT patients and MRD+ or -/ST patients. The
percentages of the T/NK-cell subsets in the PB were not significantly different
among these groups. Thus, the difference of the possible T/NK-cell phenotype in
the BM may strongly influence clinical and molecular remission. These results
still remain to be confirmed by further studies of the functional anti-tumor
immunity of T/NK cells of AML in remission.
PMID- 9643571
TI - Is multidrug resistance (P-glycoprotein) an intrinsic characteristic of plasma
cells in patients with monoclonal gammopathy of undetermined significance,
plasmacytoma, multiple myeloma and amyloidosis?
AB - Multiple myeloma is not a curable disease, and most patients relapse after
plateau phase. Drug resistance is a major problem in effective chemotherapy in
this kind of disease. Current approaches are aimed at reversing or preventing
drug resistance late in the disease. We studied a drug resistance marker, P
glycoprotein (P-gp), in a total of 43 patients with monoclonal gammopathy. This
group included eight with monoclonal gammopathy of undetermined significance
(MGUS), five with plasmacytoma (PCM), nineteen with multiple myeloma (MM; six
newly diagnosed, seven plateau, five refractory, one relapse) and eleven
amyloidosis (seven newly diagnosed, four after treatment). Using 3-color flow
cytometry, a plasma cell gate was selected on the basis of CD38+/45-(dim)
staining and the population was examined for the expression of P-gp using two
monoclonal antibodies (MRK16 and UIC2). P-gp expression was positive on marrow
plasma cells in 42/43 patients. The resistance index (RI) in these cases (range
2.0-7.07) is comparable to that in the positive cell line KG-1A (3.05-3.08). In 2
of 5 patients with refractory MM, the RI for P-gp (5.4, 6.36) was higher than in
plateau phase. These data suggest that relative resistance due to the P-gp
mechanism is likely to be an intrinsic property of plasma cells in monoclonal
gammopathies and may provide a partial explanation as to why these diseases
always relapse. The results of our study support strategies for MDR reversal
earlier in the course.
PMID- 9643572
TI - Intravascular lymphomatosis--an indolent or aggressive entity?
AB - Intravascular lymphomatosis (IVL) is a rare malignancy characterized by
neoplastic proliferation of lymphoid cells within the lumens of arteries, small
veins and capillaries. We report four patients with IVL and review the recent
world literature, relating to incidence, clinical features and possible therapy.
In these cases diagnosis was established coincidentally in one patient after
prostatectomy. This patient eventually had central nervous system involvement. In
two other patients IVL was diagnosed from skin lesions. In the fourth case the
diagnosis was established at post-mortem examination, where involvement of most
organs was evident but particularly kidneys, myocardium, gastrointestinal tract
and lymph nodes. Therapy was given to three patients, but the disease progressed
in two and they both died with evidence of central nervous system involvement,
while the third patient has had a good partial response to combination
chemotherapy but has relapsed within two months of completing chemotherapy. As
evident from our patients and the literature review IVL has a variable clinical
course and currently, there appears to be no effective therapy for this rare
disorder.
PMID- 9643573
TI - p53 mutation in a case of blastic transformation of follicular lymphoma with
double bcl-2 rearrangement (MBR and VCR).
AB - The bcl-2 gene is rearranged in most cases of follicular lymphoma and the
breakpoint clusters are found in two specific regions: mbr and mcr.
Rearrangements of the immunoglobulin heavy chain genes (IgH) result in a
deregulation of the gene and increased transcription of mRNA for the bcl-2
protein. In cases of rearrangement of the light chains (variant translocations),
a third breakpoint has been described at the 5' part of the bcl-2 locus (vcr). In
the present case, we report the molecular analysis of an FL transformed into a
blastic phase unresponsive to chemotherapy. Molecular studies revealed a typical
bcl-2 rearrangement at the major locus (mbr). Vcr rearrangements was also
observed with only a single restriction enzyme. At the same time, SSCP analysis
of exon 5 of the p53 locus disclosed an abnormal conformer. Direct sequencing
revealed a point mutation at codon 163 (A --> G). Immunohistochemical analysis of
the affected sites disclosed overexpression of p53 and bcl-2. It is concluded
that p53 mutation can contribute to blastic transformation in cases of follicular
lymphomas with double rearrangement at the bcl-2 locus (mbr/vcr).
PMID- 9643574
TI - P53 gene mutation in a T-acute lymphoblastic leukemia cell line (loucy) with
t(16:20) and 5q- chromosomal aberrations.
AB - A human T-acute lymphoblastic leukemia (ALL) cell line (Loucy), derived from
cells from a patient with resistant ALL with a t(16:20) and 5q- chromosomal
aberrations was evaluated for p53 gene alterations and expression. Western blot
analysis of p53 showed elevated levels of the protein. Reverse transcriptase
polymerase chain reaction (RT-PCR) analysis and direct sequencing identified a
point mutation at codon 272 (GTG --> ATG) of the p53 gene. Possible molecular
mechanisms underlying these alterations and their role in the establishment of
this cell line and in leukemogenesis in general are discussed.
PMID- 9643575
TI - Spontaneous splenic rupture in a patient with acute lymphoblastic leukemia of
Burkitt type.
AB - We describe a case of spontaneous splenic rupture occurred in a patient with
acute lymphoblastic leukemia of Burkitt type before starting cytotoxic
chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was
the only clinical symptom. Emergency computed tomography showed splenic
laceration and hemoperitoneum. The patient underwent immediate laparatomy with
splenectomy and experienced an uneventful postoperative recovery. Eight days
after surgery, chemotherapy could be administered and complete remission was
achieved. Although spontaneous rupture of the spleen is rare in leukemia and
related disorders, this diagnosis should be taken in account also when clinical
symptoms are mild. Following immediate operative management, patients may
completely recover and receive cytotoxic chemotherapy with substantial
possibilities of achieving complete remission.
PMID- 9643576
TI - Dramatic resolution of pleural effusion in children with chronic myelomonocytic
leukemia following short-course high-dose methylprednisolone.
AB - High-dose methylprednisolone (HDMP) which can induce--differentiation and
apoptosis of myeloid leukemic cells has been shown to be very effective in the
treatment of extramedullary infiltration (EMI) of children with acute
myeloblastic leukemia (AML). In the present study 2 children with chronic
myelomonocytic leukemia (CMML) who had pleural effusions were given a single
daily dose of oral methylprednisolone (20 mg/kg or 30 mg/kg). In addition to
dramatic improvement of respiratory symptoms, pleural effusions disappeared in
four days in both patients possibly due to apoptotic cell death induced by HDMP
treatment. Further studies are needed to determine whether high-dose
corticosteroids are also effective on the resolution of pleural effusions
associated with other malignant disease.
PMID- 9643577
TI - Spontaneous acute tumor lysis syndrome in acute myeloid leukemia? A single case
report with discussion of the literature.
AB - Acute tumor lysis syndrome (ATLS), a condition which results from a rapid
destruction of tumor cells with massive release of cellular breakdown products,
has been well described following the treatment of various malignancies. However,
only a handful of cases of spontaneous ATLS have been reported in the literature.
We describe the first reported case of spontaneous ATLS in acute myeloid leukemia
(AML). A previously healthy 63 year old woman presented with a two month history
of fatigue and a one week history of easy bruising. On admission she had oliguric
acute renal failure, with marked elevation in serum uric acid and phosphate. A
bone marrow biopsy showed AML M7 with fibrosis. The renal failure resolved with
supportive care and institution of allopurinol therapy. Following this, AML
induction chemotherapy resulted in complete remission. Her biochemical and
clinical course were very similar to the classical ATLS seen in patients after
chemotherapy. Therefore, this case represents a rare instance of acute renal
failure from spontaneous ATLS, and in our opinion the first reported occurrence
of spontaneous ATLS associated with AML.
PMID- 9643578
TI - Induction of apoptosis by bleomycin in resting and cycling human lymphocytes.
AB - Bleomycin induces DNA and chromosome breakage. The differential sensitivity to
the drug has been used in vitro to identify individuals at high risk of
developing tumours. However, there are limited reports on the ability of
bleomycin to induce apoptosis. In this study we tested induction of apoptosis in
human peripheral lymphocytes by bleomycin at different concentrations and
different culture times using various parameters, such as nuclear fragmentation
and DNA fragmentation, evaluated either in situ with terminal transferase and
labelled nucleotides (TUNEL) or by flow cytometry analysis. We demonstrate that
bleomycin induces apoptosis without previous permeabilization of the cell
membrane. Cell death occurs mainly by apoptosis and not by necrosis, with
significant alteration of membrane lipoperoxidation (evaluated by luminescence).
PMID- 9643579
TI - Frequency, distribution and clonality of chromosome damage in human lymphocytes
by multi-color FISH.
AB - Whole chromosome painting was used to determine whether the use of different sets
of paints would influence results obtained from the analysis of human peripheral
blood lymphocytes from 27 healthy unexposed subjects. Painting was also used to
determine if aberration frequencies are proportional to the size of selected
chromosomes in human lymphocytes irradiated in vitro. The in vitro results showed
that the frequencies of radiation-induced stable aberrations (i.e. translocations
and insertions) in chromosomes 3, 5 and 6 painted in unique colors are
proportional to chromosome size. Aberration frequencies in the normal subjects
were measured using two different sets of paints, one set for chromosomes 3, 5
and 6 where each chromosome was labeled in a unique color and one set where
chromosomes 1, 2 and 4 were painted in a single color. The frequency of
aberrations among chromosomes 1-6 in the population as a whole was also found to
be proportional to chromosome size. However, some individual subjects had a
distribution of damage that was not proportional to chromosome size due to the
presence of clones of abnormal cells. Aberration frequencies measured in
chromosomes 3, 5 and 6 as a set were highly correlated with those observed in
chromosomes 1, 2 and 4 as a set, after adjusting for the different amounts of the
genome that were painted. We also determined whether differences exist in the
aberration frequencies measured by two scoring systems: the classical method,
where reciprocal exchanges are scored as single events, and PAINT, where each
break junction is scored as a single event. The two scoring systems gave highly
correlated results for translocations and differed by a constant value (PAINT x
0.58 = classical method). Approximately 27% of translocations were observed to be
non-reciprocal due to a failure to detect exchanges involving small amounts of
material or to a non-reciprocal exchange mechanism. Our results support the
hypothesis that cytogenetic evaluations for biodosimetry can be performed with
any one or more of the chromosomes studied here and indicate that the aberration
frequency measurements are independent of the scoring system selected for the
evaluation. We also present a simple statistical method for identifying subjects
that may possess clonal aberrations.
PMID- 9643580
TI - Sodium arsenite-induced chromosomal aberrations in the Xq arm of Chinese hamster
cell lines.
AB - Non-cytotoxic concentrations (1.5, 3 and 6 microM) of sodium arsenite (SA) were
used to study its cytogenetic effects with special reference to the frequency and
nature of chromosomal aberrations on the X chromosome at Xq21 and at centromeric
regions in CHO9, EM-C11, V79, V-H4 and CHE cell lines using Giemsa and FISH
techniques. A high frequency of chromosomal breakpoints was distributed on the X
chromosome localized at the secondary constriction region of the q arm (Xq21) and
to a lesser degree at the centromeric region (c band-positive region), showing a
high degree of fragility of these regions. This phenomenon was observed in all
cell lines except for V79, where aberrations were localized only in the Xq21
region, and CHO9, where the observed breakage frequency was lowest in comparison
with other cell lines and breaks were mostly located in the centromeric region
rather than at Xq21. Homozygous expression of the breakpoint at Xq21 (fragile
site) and in the centromeric region was also confirmed using a female Chinese
hamster embryonic (CHE) cell line, which showed a similar high frequency of
breakpoints at Xq21 and in the centromeric region of both X chromosomes. Further,
a detailed cytogenetic study in CHO9 and its ligase-deficient mutant EM-C11 cell
line showed slightly higher sensitivity to SA in a cell survival assay. No
difference was found for chromosomal aberrations in Giemsa stained preparations.
For SCEs a higher spontaneous frequency was evident in EMC-11. SA significantly
increased the frequency of SCEs in CHO9, but no effect was found in EM-C11.
Further, we observed an increased number of abnormal cells with pulverised
chromosomes, decondensed chromatin, isochromosomes and hyperploidy in CHO9 and EM
C11 cell lines at all doses of SA.
PMID- 9643581
TI - Frequencies of occurrence of all human chromosomes in micronuclei from normal and
5-azacytidine-treated lymphocytes as revealed by chromosome painting.
AB - Chromosome painting with library DNA probes specific for all human chromosomes
was used to study the chromosomal content of micronuclei (MN) in normal and 5
azacytidine (5-aza-C)-treated lymphocyte cultures. More than 60,000 normal
lymphocytes were screened for associated MN after in situ hybridization. At least
50 MN were scored for each probe. With the exception of chromosomes 12 and 19,
which did not occur in MN, all other chromosomes were detected in MN at
frequencies varying from 1 to 11.5%. Treatment of lymphocyte cultures with 5-aza
C induced preferential exclusion of chromosomes 1 (34%), 9 (32%) and 16 (20%)
material in MN, whereas chromosome 8, 10, 12-15 and 21 material was not detected
in MN. The results obtained from normal lymphocytes allow for the first time an
estimation of the frequency of occurrence of all chromosomes in spontaneously
occurring MN in human cells. Data derived from 5-aza-C-treated lymphocytes are
furthermore consistent with the view that undermethylation of heterochromatin may
be associated with loss of specific chromosomes at metaphase.
PMID- 9643582
TI - Influence of buthionine sulfoximine and reduced glutathione on arecoline-induced
chromosomal damage and sister chromatid exchange in mouse bone marrow cells in
vivo.
AB - Arecoline (ARC), an alkaloid of the betel nut (Areca catechu), is a major
ingredient of betel quid. The carcinogenic potentiality as well as its cell
transformation ability has already been reported. Reduced glutathione (GSH), a
major non-protein thiol substance plays an important role in protection of cells
against the toxic effect of exogenous compounds. In order to understand the role
of factors which affect ARC sensitivity, we have made an attempt to establish a
relationship between ARC-induced DNA damage and the endogenous GSH status of the
cells. ARC was administered to untreated and buthionine sulfoximine (BSO) (a GSH
depleting agent)-treated mice. Exogenous GSH was also added to ARC-administered
mice. Cells were fixed at 20 h and both chromosome aberrations (CAs) and sister
chromatid exchanges (SCEs) were scored. Both CAs and SCEs were significantly
induced by ARC and the frequency of both these parameters were increased further
when ARC was given to BSO-treated mice. However, GSH reduced the frequency of CAs
induced by ARC but failed to do so for SCEs. The data indicate that ARC-induced
DNA damage is influenced by endogenous GSH level. The failure of GSH to reduce
the frequency of SCEs indicates that the mechanism of induction of CAs and SCEs
by ARC are different.
PMID- 9643583
TI - Statistical analysis of lacZ mutant frequency data from MutaMouse mutagenicity
assays.
AB - Transgenic mouse assays have provided an unprecedented opportunity to study
mutagenesis in diverse rodent tissues. In this article data from MutaMouse
mutagenicity assays based on the Escherichia coli gene lacZ were analyzed
systematically using liver and bone marrow as potential target tissues. Sources
of variation, including plates (within packaging reactions), packaging reactions
(within animals) and animals, were evaluated for extra-binomial variation.
Although hardly any evidence of overdispersion was detected at the plate level,
limited evidence of extra-binomial variation was observed at the packaging
reaction level. There was, however, much stronger evidence of overdispersion at
the animal level. Statistical tests for increasing trend in mutant frequency with
increasing dose were also performed at the animal level. A significant increasing
trend following exposure to N-nitrosodibenzylamine was detected in liver but not
in bone marrow. A logistical model was used to further describe the dose-response
relationship observed in N-nitrosodibenzylamine-treated liver tissue.
PMID- 9643584
TI - Distribution of camptothecin-induced break points in Chinese hamster cells
treated in late S and G2 phases of the cell cycle.
AB - The distribution of camptothecin (CPT)-induced break points in late S or G2 phase
of the cell cycle observed in Chinese hamster chromosomes was analysed in 400
metaphases. Contrary to expectation, they were not localized in the
heterochromatic regions, suggesting that these chromatid-type aberrations arise
by a mechanism which does not involve collision of the CPT-trapped 'cleavable
complex' with the replication fork. Since many break points mapped more
frequently to light bands (DAPI negative) than dark bands (DAPI positive) with a
frequency of 73 and 15% respectively, it could be argued that the presence of the
CPT-trapped 'cleavable complex' probably interferes with chromatin condensation.
In fact, the euchromatic regions, which are expected to be more actively
condensed in G2 phase, were more involved in chromosomal damage. These results do
not completely confirm the idea that some residual DNA synthesis occurring in G2
is responsible for the G2 clastogenic effects of CPT as the heterochromatic
regions should, in this case, be more involved.
PMID- 9643585
TI - Expression of human cytochrome P450 1A2 in Escherichia coli: a system for
biotransformation and genotoxicity studies of chemical carcinogens.
AB - In this study we describe the development of strain BMX100, a new Escherichia
coli K12 tester strain, derived from MX100, a strain which was constructed for
detection of mutagens and for mechanistic studies of chemical carcinogens. We
demonstrate here that strain BMX100 can be used for stable expression of human
CYP1A2 or human CYP1A2 fused to rat liver NADPH cytochrome P450 reductase.
Mutagenicity of precarcinogens known to be bioactivated by CYP1A2, namely 2
aminoanthracene (2-AA), aflatoxin B1 (AFB1) and 2-amino-3-methylimidazo[4,5
f]quinoline (IQ), could be detected. The mutagenic activity of 2-AA using BMX100
expressing CYP1A2 alone and in combination with rat CYP reductase was
respectively 10 and 20 times higher than in BMX100 with the standard metabolic
activation system, rat liver S9 fraction. Furthermore, the mutagenicity of 2-AA
could be nullified by alpha-naphthoflavone, a known inhibitor of CYP1A2. IQ
responded equally in BMX100 expressing the CYP1A2-reductase fusion protein as
compared with usage of rat liver S9 fraction. Rat liver S9 fraction was much more
potent in generating a mutagenic response to AFB1 in BMX100 than in the strain
expressing human CYP1A2 alone or CYP1A2 fused to rat reductase. The results
described in this study demonstrate that this new E.coli strain can function as a
human CYP1A2-competent prokaryotic mutagenicity test system and they seem to
characterize BMX100 as a strain of interest for studies to identify individual
human CYPs involved in bioactivation and bioinactivation reactions of putative
genotoxins.
PMID- 9643586
TI - Structural features of tannic acid important for DNA degradation in the presence
of Cu(II).
AB - Tannic acid has numerous food and pharmacological applications. It is an additive
in medicinal products and is used as a flavouring agent and as an antioxidant in
various foods and beverages. However, there are reports of its mutagenicity and
carcinogenicity in bacterial and animal test systems. Tannic acid and its
structural monomer gallic acid are also capable of inducing apoptosis in animal
cells. We have earlier shown that tannic acid in the presence of Cu(II) causes
DNA degradation through generation of reactive oxygen species such as hydroxyl
radicals. In order to understand the chemical basis of the various biological
properties of tannic acid we have studied the structure-activity relationship
between tannic acid and gallic acid using the DNA cleavage assay. Results in the
present paper indicate that gallic acid is considerably more active than tannic
acid. However, if two of the three hydroxyl groups of gallic acid are methylated
(syringic acid) the DNA degrading capacity declines sharply. Further,
decarboxylation of gallic acid (pyrogallol) leads to enhancement of its activity.
In conclusion, the results indicate that the DNA cleavage activity of tannic acid
is due to its digalloyl moeity and that free hydroxyl groups are essential for
cleavage.
PMID- 9643587
TI - Structural and numerical chromosomal aberrations in a metabolically competent
human lymphoblast cell line (MCL-5).
AB - MCL-5 cells are Epstein Barr virus-transformed human lymphoblasts which have been
genetically engineered for use in mutagenicity testing. We have examined the
modal chromosome number, karyotype and spontaneous micronucleus (MN) and sister
chromatid exchange (SCE) frequencies of the cell line. Replicate experiments were
conducted on two different shipments purchased from Gentest Corp. Although the
modal chromosome number was 48 (range 40-54, n = 400 metaphases) for both cell
shipments, the second stock showed greater variation in chromosome number than
the first. A total of 60 G-banded metaphase cells was analyzed and seven
karyotypes were prepared. Consistent structural abnormalities (translocations,
deletions and isochromosomes) were found involving the X chromosome and seven
autosomes (1-3, 5, 6, 9 and 11). The karyotype typical of this cell line was:
48,der(X)t(X;?)(p22.3;?)Y,t(1;2)(q23;p23),del(3)(q12q21), + i(3q),t(5;6)
(q31;p23),+i(9p),der(11)t(11;13)(q23;q12). The mean MN frequency was 41.8 MN/1000
binucleate cells (n = 5000). When compared with our historical controls for
primary lymphocyte cultures this number (41.8) is significantly (8.4-fold)
higher. The mean SCE frequency was 7.3 per metaphase (n = 100). We observed a
hyperdiploid chromosome number of 48 in the majority of metaphase spreads,
indicating a significant deviation from the normal diploid number characteristic
of the parent cells (RPMI 1788) established in 1969. The variation in chromosome
number distribution observed between shipments suggests the potential for further
changes. The elevated MN frequency suggests that evaluating mutagenicity using
this cytogenetic end-point may require excessive dosing to produce a significant
response over background. We conclude that careful interpretation of cytogenetic
end-points is necessary when using MCL-5 cells in the light of the possibility of
clonal evolution presented here.
PMID- 9643588
TI - Heterogeneity of the DNA damage provoked by antimony and arsenic.
AB - Data on the mechanism of antimony genotoxicity is scarce. Arsenic and antimony
are proposed to share some toxicological features. Thus comparative and combined
experiments with As(III) and Sb(III) were performed to gain a deeper knowledge of
the mechanism of antimony genotoxicity. Trivalent arsenic proved to be five times
more cytotoxic and one order of magnitude more potent in induction of micronuclei
in human lymphocytes in vitro than was antimony. Significantly increased
micronucleus frequencies were achieved with As(III) at a dose of 0.5 microM and
with Sb(III) at a dose of 5 microM. Neither the number of micronuclei induced by
As(III) nor by Sb(III) could be suppressed by co-incubation with superoxide
dismutase or catalase. This suggests that induction of oxidative stress may not
be a crucial step in the mechanism of DNA damage induction by arsenic and
antimony. The combined genotoxicity in micronucleus test co-incubation
experiments with arsenic and antimony seemed best described by simple additivity.
In the single cell gel test with human lymphocytes a significant induction of DNA
damage was observed with 0.01 microM As(III) and 5 microM Sb(III). In contrast to
Sb(III), As(III) proved to be a very potent inducer of DNA-protein crosslinks. It
may be that Sb(III) as well as As(III) causes DNA damage by inhibition of enzymes
involved in DNA repair. Further investigations will have to identify the relevant
sites of action.
PMID- 9643589
TI - Genotoxic lipid peroxidation products: their DNA damaging properties and role in
formation of endogenous DNA adducts.
AB - The peroxidation of polyunsaturated lipids generates a range of substances that
possess DNA damaging potential. This includes lipid hydroperoxides and various
species that contain unpaired electrons, such as the alkoxyl and peroxyl
radicals. In addition, a range of genotoxic carbonyl-containing compounds are
formed, such as malondialdehyde, various 4-hydroxy-2-alkenals such as 4
hydroxynonenal and a number of 2-alkenals. It has previously been assumed that
the antioxidants and electrophile scavenging enzymes existing in mammalian cells
effectively protect the genetic material against these substances. However,
thanks to recent analytical advances in the detection of low levels of DNA
adducts, it is now evident that DNA adducts formed from a range of lipid
peroxidation products are abundant in both rodent and human genomes. This
suggests that the cellular defence system is not 100% efficient and that a
proportion of endogenously produced lipid peroxidation products escape
detoxification and cause DNA damage. This review surveys the genotoxic properties
of the major classes of lipid peroxidation products, focusing on their chemistry
of DNA adduction, the mutagenic properties of such damage and the evidence that
it occurs in intact biological systems. Furthermore, avenues of future research
that will clarify the significance of such damage to spontaneous mutagenesis and
carcinogenesis are proposed and discussed.
PMID- 9643590
TI - Cleft care: life after CSAG. Clinical Standards Advisory Group.
PMID- 9643591
TI - Human recombinant BMP-2 in osseous reconstruction of simulated cleft palate
defects.
PMID- 9643592
TI - Functional treatment of craniosynostoses during childhood.
AB - The aim of this article was to present a treatment strategy for complex
craniosynostoses, such as Apert syndrome and Crouzon's disease, based on the
author's experience of over 16 years. The most favourable results of primary
decompression have been achieved by the radical osteoclastic procedure described
by Powiertowski. Subsequent frontal advancement and Le Fort III osteotomy are
necessary in these patients when they reach 6-10 years of age. Orthopaedic
treatment with a Delaire mask should be started immediately after the operation
to achieve optimal growth of the skull base with anterior rotation of the maxilla
and posterior rotation of the mandible, which leads to a much better result.
PMID- 9643593
TI - Head and neck cancer services: views of patients, their families and
professionals.
AB - OBJECTIVES: To explore views of patients, their families and professionals about
head and neck cancer services. METHODS: Focus group interviews of 33 patients and
relatives and 33 professionals from four hospitals and two patient support groups
in SouthEast England. RESULTS: Although patients and relatives were grateful for
their care, many thought that some areas could be improved. Many thought that
their ward facilities were inappropriate. Patients wanted to have more
information about the impact of their treatment and about different treatment
options whereas professionals tended to concentrate on giving information about
the details of operations. Counselling services were often found to be
inaccessible and inappropriate. Administrative difficulties were a major source
of frustration for professionals, as were failure of treatment and communication
difficulties. Professionals valued joint clinics and a team approach in keeping
up to date, in clinical decision making, and in providing mutual support.
CONCLUSION: The findings highlight areas that could be improved which would
benefit both patients and professionals.
PMID- 9643594
TI - Cross-matched blood for major head and neck surgery: an analysis of requirements.
AB - We retrospectively analysed our blood ordering practice; the number of units of
cross-matched blood requested was compared with the number transfused, in 70
patients undergoing a total of 82 ablative operations for malignant disease.
Patients undergoing neck dissection alone, or excision of tumour with free
revascularized flap reconstruction without neck dissection, are unlikely to
require blood transfusion. Operations that include excision of tumour with
primary closure and neck dissection, excision of tumour with pedicled flap
reconstruction and excision of tumour with any form of flap reconstruction and
neck dissection in continuity, will probably require transfusion. If atypical
antibodies are present in the patient's serum on screening, cross-matched blood
should always be available preoperatively. Provided that atypical antibodies are
not present and that blood is available within 40 minutes from the blood bank,
our results show that it is safe to adopt a policy of blood grouping and saving
serum, for patients undergoing neck dissection alone, but cross-matching two or
more units of blood for patients who are to have more extensive operations.
PMID- 9643595
TI - Dental extractions in patients on warfarin: is alteration of anticoagulant regime
necessary?
AB - Various clinical protocols for the management of warfarinised patients needing
dental extractions have been suggested. This study was designed to compare two
approaches in the management of these patients. A control group of 32 patients
had their warfarin treatment stopped for 2-3 days prior to having dental
extractions, resulting in a reduction in the average preoperative international
normalised ratio (INR) from 2.6 to 1.6. The study group of 33 patients did not
have their anticoagulant treatment altered before extractions, and had an average
preoperative INR of 2.7. All patients were treated under local analgesia on an
outpatient basis, and local measures-consisting of Surgicel pack and sutures-were
used in all cases to control postoperative bleeding from extraction sockets. None
of the patients had any immediate postoperative bleeding, and only 1 patient from
each group had mild delayed haemorrhage, which was easily controlled with local
measures. It is proposed that, provided the INR is within the therapeutic range
of 2.0 to 4.0 and local measures are used to control postoperative bleeding,
there is no justification in altering warfarin treatment prior to dental
extractions in these patients, and thereby exposing them to the risk of
thromboembolism.
PMID- 9643596
TI - von Willebrand disease and its management in oral and maxillofacial surgery.
AB - von Willebrand disease (vWD) is the most common of the hereditary disorders of
coagulation. We describe the pathophysiology, diagnosis and the new simplified
classification of the disorder and discuss the management of patients about to
undergo dental procedures and maxillofacial surgery. Close collaboration between
oral and maxillofacial surgeons and haematologists in the management of patients
with vWD is essential.
PMID- 9643597
TI - Atypical cervico-facial mycobacterial infections in childhood.
AB - We describe three patients who presented with atypical mycobacterial infection.
Although antituberculous drugs are ineffective, combination treatment with
clarithromycin or amikacin and ciprofloxacin (with or without cotrimoxazole)
leads to eventual resolution of the lesions. The treatment of choice, however,
remains complete excision of the affected area which obviates the need for
prolonged chemotherapy and minimizes the scarring which may otherwise develop
after conservative treatment.
PMID- 9643598
TI - Five-year results of maxillary intramobile Zylinder implants.
AB - We retrospectively analysed the time-dependent function of 501 Intramobile
Zylinder (IMZ) implants inserted between August 1983 and December 1994 to restore
partially and fully edentulous maxillae. To ensure the independence of implants
when calculating level of significance, we chose one implant per patient at
random. This was done 500 times to obtain a representative result. The simplified
success rate was 473/501 (92%) whereas the time-related survival probability was
76% after 60 months. In 31% (156/500) of the life-table calculations, implants
placed in completely edentulous maxillae showed a significantly lower probability
of survival than did those placed in partially edentulous patients (P mean: 0.17;
SD: 0.19). Implants, that had been placed in the anterior and premolar regions of
edentulous maxillae, had a survival probability of 60%, after 60 months. The
survival probability of implants placed in the molar region was 100%, over the
same observation period. The patient's age, sex, and the time of placement of the
implant after tooth extraction had no significant influence on the implant's
prognosis. The prognosis of implants inserted for partial edentulism meets the
criteria proposed for a viable implant system. Our findings indicate that in
complete edentulous maxillae, implants should be placed in the posterior rather
than in the anterior region, even though this necessitates augmentation
procedures such as sinus lift.
PMID- 9643599
TI - Desmoplastic variant of ameloblastoma in Chinese patients.
AB - Desmoplastic ameloblastoma is a rare tumour, and we know of only 43 previously
reported cases. We report seven Chinese patients (five men and two women) with
the desmoplastic variant of ameloblastoma, which makes up 9% of all
ameloblastomas diagnosed during the years 1981-1995. The age ranged from 18 to 68
years (mean 43). Five of the tumours were in the maxilla and two were in the
mandible. Five of them were situated anteriorly, the remaining two cases
involving both anterior and posterior maxilla. The features of the 42 cases
previously reported were reviewed and were compared with those in the present
study. Our results differ in that we found a male predominance, wider age range
and more tumours in the maxilla. Histologically, this variant of ameloblastoma is
characterized by abundant collagenous stroma. Because the epithelial clusters may
show prominent squamous metaplasia or may be compressed into thin strands in most
areas, the appearance may mimic a squamous odontogenic tumour or odontogenic
fibroma. The behaviour of this variant of ameloblastoma is likely to be the same
as that of the classic ameloblastoma.
PMID- 9643600
TI - Simple X-ray film holder for lateral view of the anterior jaws using dental X-ray
apparatus.
AB - A new X-ray apparatus, the occlusal X-ray film holder, was devised so that the
lateral view of the jaw could be studied. This apparatus could easily be adjusted
to a dental X-ray cone. In 21 cases of impacted teeth, cysts or foreign body in
the maxilla and mandible and 6 cases that necessitated examination before or
after implantation, the efficacy of this apparatus was confirmed. Its advantages
are: it is applicable to dental X-ray equipment; it is cheap; there is no need
for image intensifying to get a clear image; and follow-up examination is
possible. We believe that this film holder would be useful for the diagnosis of
lesions in the anterior maxilla and mandible as well as in the general dental
clinic.
PMID- 9643601
TI - A recessively inherited non-lethal form of popliteal pterygium syndrome.
AB - Two siblings, a 10-year-old boy and a 6-month-old girl, born in a Palestinian
family, with manifestations of popliteal pterygium syndrome are presented. This
rare form of syndrome is usually assumed to be autosomal dominant. Parental
consanguinity and lack of phenotype manifestation in the ancestry of the present
family favoured an interpretation of determination by an autosomal recessive
trait.
PMID- 9643602
TI - Latex foam and staple fixation of skin grafts.
AB - Skin grafts are time consuming to secure effectively. We report our experience
with a simple, versatile and rapid technique utilising staples and a latex foam
dressing.
PMID- 9643603
TI - Combined use of titanium mesh and biocompatible osteoconductive polymer in the
treatment of full thickness calvarial defects.
AB - Restoration of bony defects is a common problem in craniofacial surgery. This
article describes a versatile approach using a combination of titanium micromesh
or midimesh and biocompatible osteoconductive polymer to restore calvarial bone
loss.
PMID- 9643604
TI - Prevention of microstomia following facial burns.
PMID- 9643605
TI - Citation for the Down Surgical Prize 1996 to Richard Haskell.
PMID- 9643606
TI - Citation for the De Puy Surgical Prize 1996 to Mike Corrigan.
PMID- 9643607
TI - Isolated incident involving an assault with a bamboo cane.
PMID- 9643608
TI - Combined radial forearm and pharyngeal flaps for soft palate reconstruction.
PMID- 9643609
TI - Failed pharyngoplasty.
PMID- 9643610
TI - Protection of the lingual nerve.
PMID- 9643611
TI - Pharmacovigilance: towards the next millennium.
PMID- 9643612
TI - Use of the UK General Practice Research Database for pharmacoepidemiology.
AB - The last decade has seen a surge in the use of computerized health care data for
pharmacoepidemiology. Of all European databases, the General Practice Research
Database (GPRD) in the UK, has been the most widely used for
pharmacoepidemiological research. Since 1994, this database has belonged to the
UK Department of Health, and is maintained by the Office of National Statistics
(ONS). Currently, around 1500 general practitioners with a population coverage in
excess of 3 million, systematically provide their computerized medical data
anonymously to ONS. Validation studies of the GPRD have documented the recording
of medical data into general practitioners' computers to be near to complete. The
GPRD collects truly population-based data, has a size that makes it possible to
follow-up large cohorts of users of specific drugs, and includes both outpatient
and inpatient clinical information. The access to original medical records is
excellent. Desirable improvements to the GPRD would be additional computerized
information on certain variables and linkage to other health care databases. Most
published studies to date have been in the area of drug safety. The General
Practice Research Database has proved that valuable data can be collected in a
general practice setting. The full potential of this rich computerized database
has yet to come. This experience should serve to encourage others to develop
similar population-based data in other countries.
PMID- 9643613
TI - Pharmacovigilance in the pharmaceutical industry.
PMID- 9643614
TI - Nitric oxide in the human cardiovascular system--SKB lecture 1997.
PMID- 9643615
TI - Endothelin-1 induces vasodilation in human skin by nociceptor fibres and release
of nitric oxide.
AB - AIMS: Endothelin is a peptide produced by endothelial cells with many biological
properties. In the human skin microcirculation endothelin induces neurogenic
vasodilation associated with burning pruritus. We investigated the mechanisms
involved in this response. METHODS: The effects of prolonged pretreatment with
capsaicin, a specific inhibitor of polimodal nociceptor fibres, and of the nitric
oxide synthase inhibitor L-NMMA on endothelin-1-induced vasodilation were studied
in 15 human subjects. Furthermore, we investigated the effects of the ET(A)
selective antagonist PD147953 on bradykinin-induced vasodilation. RESULTS: After
local injection, endothelin-1 caused vasoconstriction at the injection site and a
profound vasodilation in the surrounding area (flare reaction, P<0.01). This
response was specific and not induced by saline, albumin, acetylcholine or an ET
antagonist. Prolonged capsaicin pretreatment inhibited endothelin-1 induced
vasodilation in the area surrounding the injection site, but not the central
vasoconstriction at the injection site. Bradykinin also induced a marked
vasodilation in the area surrounding the injection site; this was not inhibited
by an ETA-selective antagonist, while the flare reaction was. L-NMMA applied at
the site of the flare reaction prevented endothelin-1-induced vasodilation.
CONCLUSIONS: Endothelin-1 in the human skin microcirculation stimulates polimodal
nociceptor fibres leading to the release of nitric oxide. This response may play
a pathophysiological role in inflammatory processes in the human skin.
PMID- 9643616
TI - The influence of nifedipine and captopril on liver blood flow in healthy
subjects.
AB - AIMS: Application of single methods to assess liver blood flow (LBF) yielded
conflicting results on the magnitude and duration of effect on LBF of oral
nifedipine and captopril. The aim of this study was to investigate the influence
of these drugs on LBF by simultaneous use of ICG infusion and echo-Doppler.
METHODS: The study was performed according to a double-blind, placebo-controlled,
randomized, cross-over design in nine healthy male volunteers. After an overnight
fast and an equilibration period, subjects received a continuous i.v. indocyanine
green (ICG) infusion for 4 h. At presumed ICG steady state (t=45 min), subjects
were dosed with oral nifedipine (20 mg), captopril (50 mg) or placebo. During the
experiment, blood sampling for ICG assay and measurement of portal venous blood
flow (echo-Doppler) took place regularly. Treatments were compared using analysis
of variance. Differences are reported with 95% confidence intervals (CI).
RESULTS: The area under the curves (AUC) for ICG over 1 h and over 3 h after
nifedipine were 15% (difference in AUC: + 0.6, + 7.0 mg l(-1) min) and 22% (+
7.0, + 28.4 mg l(-1) min) lower compared with placebo. After captopril, the AUC
values were 8-10% lower compared with placebo but the 95% CIs included zero.
Portal venous flow was 15% (+ 5, + 86 ml min(-1)) higher compared to placebo
after nifedipine but not after captopril (-3%; -49, +33 ml min(-1)). The duration
of effect on liver blood flow lasted approximately 2 h but was variable (range:
40-160 min). The time to maximal blood flow increase and the duration of effect
after nifedipine were very similar for both measures of LBF. Changes in ICG
concentrations could be reasonably well predicted from the changes in portal
blood flow. CONCLUSIONS: Nifedipine increases LBF for a substantial period of
time but the effect is variable between subjects. This effect could be detected
by both the ICG method and echo-Doppler and the findings of both methods were in
agreement. In this respect it is likely that captopril does not influence LBF in
healthy volunteers as no effect was detected with either method.
PMID- 9643617
TI - Distribution and excretion of sertraline and N-desmethylsertraline in human milk.
AB - AIMS: To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline
and N-desmethylsertraline, in breast-feeding women taking sertraline for the
treatment of depression. METHODS: Eight women (mean age 28 years) taking
sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.7 months) were
studied. Sertraline and N-desmethylsertraline in plasma and milk were measured by
high-performance liquid chromatography over a 24 h dose interval at steady-state.
M/P values were estimated from area under the plasma and milk concentration-time
curves. All milk produced was collected over the dose interval. Infant exposure
was estimated as the product of actual or estimated milk production, and average
drug concentration in milk, normalized to body weight and expressed as a
percentage of the weight-adjusted maternal dose. RESULTS: Mean milk production
was 321 ml day(-1) (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were
calculated for sertraline and N-desmethylsertraline respectively. Infant exposure
estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted
maternal dose for sertraline and N-desmethylsertraline (as sertraline
equivalents) respectively. When calculated from estimated milk production (0.15 l
kg(-1) day(-1)), infant exposure was significantly greater (P<0.0001) at 0.90%
and 1.32% for sertraline and N-desmethylsertraline respectively. Neither
sertraline nor its N-desmethyl metabolite could be detected in plasma samples
from the four infants tested. No adverse effects were observed in any of the
eight infants and all had achieved normal developmental milestones. CONCLUSIONS:
Irrespective of the method of calculation of infant exposure, the mean total dose
of sertraline and its N-desmethyl metabolite transmitted to infants via breast
feeding is low and unlikely to cause any significant adverse effects.
PMID- 9643618
TI - Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human
milk.
AB - AIMS: To characterise the transfer of venlafaxine (V) and its O-desmethyl
metabolite (ODV) into human milk by measuring milk/plasma (M/P) ratio, and to
estimate the likely dose received by a breast-fed infant. METHODS: Milk and
plasma samples were collected from three lactating women who were taking
venlafaxine for depression, and were at steady-state. In two of the patients,
venous blood and milk samples were collected 0, 1, 2, 3, 4, 6, 8 and 12 h post
dose, while in the third patient a single pair of blood and milk samples was
obtained 0.83 h post dose. A plasma sample was obtained from each of their
infants. V and ODV were measured in plasma and milk by high performance liquid
chromatography. M/P was calculated and infant dose estimated as drug
concentration in milk x a milk intake of 0.15 l kg(-1) day(-1), relative to the
weight-adjusted maternal dose. RESULTS: Mean M/P for V was 4.1 (range 2.8-4.8)
and 3.1 for ODV (range 2.8-3.8). The mean total infant dose (as V equivalents)
was 7.6% (range 4.7-9.2%) of the maternal weight-adjusted dose, with
approximately equal amounts of V (3.5%) and ODV (4.1%) in the dose. ODV (median
100 microg I(-1)) was detected in the plasma of all three infants. The infants
were healthy and showed no acute adverse effects. CONCLUSIONS: These preliminary
data show that the total dose of V and ODV ingested by breast-fed infants can be
as high as 9.2% of maternal intake. Moreover there were measurable concentrations
of ODV in the infants' plasma. We recommend that exposed infants should be
observed closely.
PMID- 9643619
TI - Assessment of hepatic blood flow using continuous infusion of high clearance
drugs.
AB - AIMS: To provide methods for the translation of the concentration-time profile of
highly cleared marker compounds into the underlying clearance and hepatic blood
flow profile. METHODS: Continuous infusion of indocyanine green or sorbitol was
used to assess the effect of the hepatic blood flow modifiers exercise,
somatostatin and octreotide. Three distinct methods are described for the
translation of concentration into flow: 1. assuming successive phases of constant
clearance 2. point to point estimation of clearance using estimates of
concentration change 3. using a parametric description of the flow profile in
combination with the differential equations describing the change in marker
concentrations. RESULTS: The marker compound concentration profiles are
adequately described using the different methods. Exercise results in a decrease
in hepatic blood flow of about 80%. Somatostatin and octreotide elicit an
indistinguishable hepatic blood flow decrease from 1.49 to 1.07 l min(-1). Return
to baseline takes much longer for octreotide (half-life 126+/-104 min) than for
somatostatin (half-life 4.29+/-3.55 min). CONCLUSIONS: Translation of
concentration profiles into clearance profiles is possible making continuous
assessment of hepatic blood flow feasible.
PMID- 9643620
TI - Pharmacokinetics of bambuterol in healthy subjects.
AB - AIMS: To study the pharmacokinetics and bioavailability of the prodrug bambuterol
and its bronchodilator moiety terbutaline in healthy subjects. METHODS: Eight
healthy subjects (four women) received intravenous doses of bambuterol and
terbutaline. On a third occasion, they, plus another four subjects, ingested oral
bambuterol as a single dose followed by repeated doses once daily for 7 days.
Plasma concentrations and urinary excretion of bambuterol and terbutaline were
measured. RESULTS: After intravenous administration, renal clearances of
bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a
five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline
0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both
substances. A similar renal clearance of bambuterol was found during oral
administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean
terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral
administration, implying that uptake was rate-limiting. Mean residence time of
terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when
terbutaline as such was infused. Generated terbutaline had a bioavailability of
36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of
the prodrug. Bambuterol was well tolerated. The mean activity of plasma
cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between
30-60% during repeated oral dosing. It virtually regained original activity
within 48 h after the last dose. CONCLUSIONS: The plasma concentration
ofterbutaline fluctuated little during repeated oral administration (mean peak:
trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow
formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make
it suitable for oral once-daily dosage.
PMID- 9643621
TI - Pharmacokinetics of bambuterol in subjects homozygous for the atypical gene for
plasma cholinesterase.
AB - AIMS: It has been assumed that both plasma cholinesterase (EC 3.1.1.8) and
oxidative enzymes are needed for optimum formation of the bronchodilator
terbutaline from its biscarbamate prodrug bambuterol. The present study aimed at
investigating the fate of bambuterol in subjects with deficient plasma
cholinesterase but with normal oxidative (CYP2D6) capability. METHODS: The
pharmacokinetics of bambuterol and terbutaline were studied in four healthy
subjects (two men and two women) being homozygous for the atypical gene for
plasma cholinesterase. Their oxidative metabolism was apparently good as they
were all rapid metabolizers of debrisoquine. Bambuterol hydrochloride 20 mg was
given orally once daily for 10 days, and plasma and urine samples were taken for
1.5 days (plasma) and 4.5 days (urine) after administration of the last dose.
RESULTS: The pharmacokinetic parameters in the present study were grossly similar
to those found in a study of bambuterol in subjects with normal plasma
cholinesterase activity (N). However, subjects with atypical cholinesterase had a
shorter terminal half-life of bambuterol (a measure of uptake rate), 4.8-12.6 h
vs 8.3-22.3 h in N, and slightly higher plasma concentrations of bambuterol
(average concentrations 1.9-3.7 nmol l(-1) vs 1.5-3.1 nmol l(-1) in N).
Peak/trough terbutaline plasma concentrations ratios (2.1-3.2) were somewhat
increased, but average plasma concentrations (8.3-14.5 nmol l(-1)) and terminal
half-life (16.5-21.8 h) of terbutaline did not differ. CONCLUSIONS: In Caucasian
populations, one subject out of 2500 is homozygous for the atypical gene for
plasma cholinesterase. The atypical enzyme has a much lower affinity for
bambuterol than the normal enzyme. Nevertheless, the subjects with atypical
cholinesterase were able to produce terbutaline as efficiently as normal
subjects. This might be explained by an altered uptake and metabolism in the
absence of plasma cholinesterase, or the importance of this enzyme for the
formation of terbutaline from bambuterol in vivo may have been overestimated.
PMID- 9643622
TI - Absorption kinetics of oral sotalol combined with cisapride and sublingual
sotalol in healthy subjects.
AB - AIMS: To study the absorption kinetics of sotalol following administration of
different formulations. A formulation which results in fast absorption might be
useful in the episodic treatment of paroxysmal supraventricular tachycardia
(SVT), atrial fibrillation (Afib) or atrial flutter (Afl). METHODS: In an open
randomized crossover study seven healthy male volunteers were given an
intravenous infusion of 20 mg sotalol, for assessing the absolute
bioavailability, an oral solution containing 80 mg sotalol, an oral solution
containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet,
which was taken sublingually. RESULTS: The addition of cisapride decreased the
time at which maximum serum concentrations were reached (tmax) from 2.79 (1.85
4.34) h to 1.16 (0.68-2.30) h (P=0.009) [95% CI: -2.59, -0.55] and increased the
absorption rate constant (ka) from 0.49 (0.31-0.69) h(-1) to 1.26 (0.52-5.61) h(
1) (P=0.017). The absolute bioavailability of sotalol was reduced by cisapride
from 1.00+/-0.15 to 0.70+/-0.26 (P=0.006), while maximum serum concentrations of
both oral solutions were not significantly different. Compared with the
sublingually administered tablet with a median tmax of 2.12 (0.89-3.28) h, the
sotalol/cisapride oral solution gave a smaller tmax (p=0.009) [95% CI: -1.64,
0.36]. The ka of the sotalol/cisapride solution was significantly (P=0.010)
larger than the ka of 0.56 (0.33-0.75) h(-1) found after sublingual
administration of the tablet. CONCLUSIONS: The sotalol/cisapride oral solution
might be suitable for the episodic treatment of SVT, Afib or Afl.
PMID- 9643623
TI - Verapamil SR and trandolapril combination therapy in hypertension--a clinical
trial of factorial design. German Hypertension Study Group.
AB - AIMS: To investigate the dose-response relationship and contribution of verapamil
SR and trandolapril given in combination once a day for the treatment of
essential hypertension. METHODS: A randomized, double-blind, placebo controlled,
factorial, 12 arm parallel group comparison with placebo, verapamil SR (120, 180
mg), trandolapril (0.5, 1.0, 2.0 mg) covering all combinations of both drugs. A 4
week placebo run-in period followed by 6 weeks of treatment. Four hundred and
fifty-six patients from office practice (22 centres) with mild to moderate
hypertension enrolled and 426 with diastolic pressure > or = 100 mm Hg at the end
of run-in period were randomized. Main outcome measures were reduction in sitting
systolic (SBP) and sitting diastolic (DBP) blood pressure. RESULTS: The
combination of verapamil SR and trandolapril, particularly verapamil SR 180 mg
and trandolapril 0.5 or 1.0 mg was significantly superior to both monocomponents
at the same dose (P<0.05). For these combinations, the adjusted mean reductions
in DBP from baseline to last visit were 14.1 and 16.0 mm Hg, respectively.
Response surface analysis provided further evidence that these combinations were
optimal for antihypertensive efficacy. All treatments were well tolerated. The
incidence of adverse events did not differ significantly between treatment
groups; the profile of adverse events on combination therapy was mild and
consistent with that of each monocomponent. CONCLUSIONS: All dosage combinations
of verapamil SR and trandolapril produced significantly greater reduction of
blood pressure than the monotherapy at the same dosage. However, verapamil SR 180
mg in combination with trandolapril 1.0 mg was the dosage with the greatest blood
pressure reduction and had the greatest effects compared with the monocomponents.
PMID- 9643624
TI - Different standards for reporting ADRs to herbal remedies and conventional OTC
medicines: face-to-face interviews with 515 users of herbal remedies.
AB - AIMS: To determine whether adverse drug reactions (ADRs) to herbal remedies would
be reported differently from similar ADRs to conventional over-the-counter (OTC)
medicines by herbal-remedy users. METHODS: Face-to-face interviews (using a
structured questionnaire) with 515 users of herbal remedies were conducted in six
pharmacy stores and six healthfood stores in the UK. The questionnaire focused on
the likely course of action taken by herbal-remedy users after experiencing an
ADR associated with a conventional OTC medicine and a herbal remedy. RESULTS:
Following a 'serious' suspected ADR, 156 respondents (30.3%) would consult their
GP irrespective of whether the ADR was associated with the use of a herbal remedy
or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult
their GP for a serious ADR associated with either type of preparation. One
hundred and thirty-four respondents (26.0%) would consult their GP for a serious
ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy,
whereas four respondents (0.8%) would consult their GP for a serious ADR to a
herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar
differences were found in attitudes towards reporting 'minor' suspected ADRs.
CONCLUSIONS: Consumers of herbal remedies would act differently with regard to
reporting an ADR (serious or minor) to their GP depending on whether it was
associated with a herbal remedy or a conventional OTC medicine. This has
implications for herbal pharmacovigilance, particularly given the increasing use
of OTC herbal remedies. The finding that a high proportion of respondents would
not consult their GP or pharmacist following ADRs to conventional OTC medicines
is also of concern.
PMID- 9643625
TI - Variability in trough plasma saquinavir concentrations in HIV patients--a case
for therapeutic drug monitoring.
PMID- 9643626
TI - Peptide siderophores.
AB - Siderophores are low molecular weight iron chelators, produced by virtually all
bacteria, fungi and some plants. They serve to deliver the essential element
iron, barely soluble under aerobic conditions, into microbial cells. Siderophores
are therefore important secondary metabolites which are very often based on amino
acids and their derivatives. Biosynthesis, transport, regulation and chemical
synthesis of natural siderophores and their analogues is of considerable interest
for the protein and peptide chemist. This review gives an overview of the
structural classes of peptidic siderophores, along with data on their
biosynthesis. On a number of representative examples, strategies and schemes of
their chemical synthesis are described.
PMID- 9643627
TI - Presentation of antigenic peptides by products of the major histocompatibility
complex.
AB - Molecules encoded by the major histocompatibility complex (MHC) are polymorphic
integral membrane proteins adapted to the presentation of peptide fragments of
foreign antigens to antigen-specific T-cells. The diversity of infectious agents
to which an immune response must be mounted poses a unique problem for receptor
ligand interactions; how can proteins whose polymorphism is necessarily limited
bind an array of peptides almost infinite in its complexity? Both MHC class I and
class II determinants have achieved this goal by harnessing a limited number of
peptide side chains to anchor the epitope in place while exploiting conserved
features of peptide structure, independent of their primary sequence. While class
I molecules interact predominantly with the N- and C-termini of peptides, class
II determinants form an extensive hydrogen bonding network along the length of
the peptide backbone. Such a strategy ensures high-affinity binding, while
selectively exposing the unique features of each ligand for recognition by the T
cell receptor.
PMID- 9643628
TI - PEGA supports for combinatorial peptide synthesis and solid-phase enzymatic
library assays.
AB - Permeable resins cross-linked with long PEG chains were synthesized for use in
solid-phase enzyme library assays. High molecular weight bis-amino-polyethylene
glycol (PEG) 4000, 6000, 8000 were synthesized by a three-step reaction starting
from PEG-bis-OH. Macromonomers were synthesized by partial or di-acryloylation of
bis-amino-PEG derivatives. Bis/mono-acrylamido-PEG were copolymerized along with
acrylamide by inverse suspension copolymerization to yield a less cross-linked
resin (Type I, compounds 6-9). Furthermore, acryloyl-sarcosin ethyl ester was co
polymerized along with bis-acrylamido PEG to obtain more crosslinked capacity
resin (Type II, compounds 13-19). N,N-Dimethylacrylamide was used as a co-monomer
in some cases. The polymer was usually obtained in a well-defined beaded form and
was easy to handle under both wet and dry conditions. The supports showed good
mechanical properties and were characterized by studying the swelling properties,
size distribution of beads, and by estimating the amino group capacity. Depending
on the PEG chain length, the monomer composition and the degree of cross-linking
the PEGA supports showed a high degree of swelling in a broad range of solvents,
including water, dichloromethane, DMF, acetonitril, THF and toluene: no swelling
was observed in diethyl ether. The PEGA resins (Type I) with an amino acid group
capacity between 0.07 and 1.0 mmol/g could be obtained by variation of the
monomer composition in the polymerization mixture. Fluorescent quenched peptide
libraries were synthesized on the new polymer using a multiple column library
synthesizer and incubated with the matrix metalloproteinase MMP-9 after it had
been activated by 4-aminophenyl mercuric acetate resulting in 67/83 kDa active
enzyme. The bright beads were separated manually under a fluorescence microscope
and sequenced to obtain peptide substrates for MMP-9. After treatment with
ethylene diamine, high-loaded resins (Type II) have been employed in continuous
flow peptide synthesis to yield peptides in excellent yield and purity.
PMID- 9643629
TI - Peptides from bovine brain: structure and biological role.
AB - Fractionation of bovine brain extracts followed by automatic Edman sequencing of
individual components resulted in identification of 107 endogenous peptides
formed from functional proteins (haemoglobin, myelin basic protein, cytochrome c
oxidase, etc) or unknown precursors. Several of the newly identified brain
peptides demonstrate different types of biological activity; some of the
substances show considerable overlap with the known biologically active peptides.
It is suggested that these peptides should participate in regulation of
extracellular and intracellular biochemical processes. A concept of 'tissue
specific peptide pool' is formulated describing a novel system of peptidergic
regulation, complementary to the conventional hormonal and neuromodulatory
systems. According to that description functional proteins provide their
proteolytically derived fragments for maintaining the tissue homeostasis by
modulating the availability of peptide receptors to respective 'true' ligands.
PMID- 9643630
TI - Maternal serum uric acid levels in preeclamptic twin pregnancies.
PMID- 9643631
TI - Obstetrical factors governing the etiopathogenesis of lambdoid synostosis.
AB - Lambdoid synostosis results in skull deformities of varying degrees characterized
by occipital flattening over the involved suture and other compensatory changes
in skull shape. Such changes include contralateral occipital bossing,
contralateral frontal flattening, ipsilateral frontal bossing, and ipsilateral
anteroinferior displacement of the pinna (ear shearing). These deformities tend
to worsen during the first year of life. The etiology has been attributed to
genetic factors and primary disorders of bone growth, in addition to secondary
effects of other diseases and modulators of the in utero environment. To
determine causal factors in the development of lambdoid synostosis, the authors
reviewed medical records of the mothers of 13 children with lambdoid synostosis
who were treated at the University Medical Center of the State University of New
York at Stony Brook. Pre- and perinatal events, prior obstetrical, gynecological,
medical, social, and family histories were considered. Births of normal infants
immediately prior to and just after the affected babies were born were selected
as controls. There is a significant association between increased duration of the
first stage of labor and the development of lambdoid synostosis. Furthermore, our
results indicate that this condition has a predilection toward male infants, and
may be associated with preterm labor.
PMID- 9643632
TI - Undetected breech presentation: impact on external version and cesarean rates.
AB - The objective of this study was to determine the impact of undetected breech
presentation on an external cephalic version program. We performed a
retrospective analysis of all external cephalic versions attempted over a 1-year
interval. We then analyzed all cesarean operations performed for the indication
of breech presentation over the same interval. Cases involving twin gestations
and premature births were excluded. We found that 21% of term breech
presentations were not detected before the onset of labor and an additional 15%
were not detected until after 38 weeks' gestation. Increased third-trimester
screening for breech presentation could potentially decrease the need for
cesarean delivery.
PMID- 9643633
TI - Significance of sporadic deceleration during antepartum testing in term
pregnancies.
AB - We have investigated the significance of single sporadic deceleration during
reactive nonstress testing in normal pregnancies at term. A prospective study was
performed during a 1-year period including 4742 nonstress tests performed between
the 38th and 42nd weeks of pregnancy in patients referred to our department for
antepartum testing and without any complication or pathology. Nonstress test
(NST) was carried out with the patient lying on her left side, and was defined as
reactive if at least two accelerations of 15 beats/min (bpm) or more lasting 15
sec were observed in a 20-min period. Sporadic deceleration was defined as a
decrease in the fetal heart rate to less than 90 bpm or a decrease of 40 bpm
below the baseline, lasting at least 2 min. The sporadic deceleration was
considered as single when only one appeared in the first 20 min of monitoring and
repeated when observed again once in at least one subsequent monitoring. Thirty
four cases of single sporadic deceleration were observed among women with
reactive NST. In 14 cases there were repeated sporadic decelerations. The
patients were divided into two groups according to the presence or absence of
repeated decelerations. Outcomes of patients with repeated sporadic decelerations
were compared with a group of 34 patients where sporadic decelerations were not
observed during the antepartum testing. A significantly higher percentage of
pathological fetal heart rate traces during labor were observed in the group of
repeated decelerations. In conclusion the presence of repeated sporadic
decelerations during a reactive NST suggests that the cause of cord compromise is
persistent and recurrent cord compression is possible. Therefore, in these cases
an increased fetal risk could be expected.
PMID- 9643634
TI - Successful fetal outcome after exposure to idarubicin and cytosine-arabinoside
during the second trimester of pregnancy--a case report.
AB - Chemotherapeutic agents administered to the mother during pregnancy may severely
jeopardize the fetus. We describe a newborn girl who had been exposed to
idarubicin and cytosine-arabinoside during the second and third trimesters of
pregnancy due to treatment of newly diagnosed acute myeloid leukemia in the
mother. The child had no structural congenital abnormalities. Adverse effects
observed were prematurity, growth retardation, mildly disturbed transaminases and
erythroblastosis, all of which were self-limiting with no permanent sequelae.
PMID- 9643635
TI - Supernumerary umbilical vein resulting in a four-vessel umbilical cord.
AB - The birth of an infant with increased number of umbilical veins is a rare event
and has been previously reported to be associated with a high incidence of major
congenital anomalies. This report documents a normal infant with two umbilical
veins resulting in a four vessel cord. A male infant (third of triplet pregnancy
resulting from multiple zygote implantation) was born at 30 weeks' gestation
weighing 1320 g.Two umbilical veins and two umbilical arteries were noted on
cannulation and X ray. Physical examination and cranial, abdominal, and cardiac
ultrasound exam were normal. One-year follow-up was normal. The birth of infant
with a four-vessel cord mandates comprehensive workup for associated anomalies
but this case indicates that such a finding is not always ominous.
PMID- 9643636
TI - Pregnancy and tuberculosis: influence of treatment on perinatal outcome.
AB - The objective of this article is to evaluate the impact of tuberculosis (TB) on
perinatal outcome in a cohort of 25 pregnant women with TB treated at the
National Institute of Perinatology (Mexico, City) from March 1990 to September
1995. They were compared with a cohort of normal pregnant women; both cohorts
were matched by age, gestational age, and socioeconomic status. For purposes of
analysis, patients with TB were further stratified into two groups: one included
9 women who started treatment either before or at the beginning of pregnancy, and
the other constituted 16 women who started treatment in either the second or
third trimester of gestation. Thirteen women (52%) had pulmonary TB, 7 (28%) had
renal infection, and the rest of patients had diverse extrapulmonary localization
of the infection. Obstetrical morbidity and neonatal mortality were significantly
higher in pregnant women with TB who started treatment late in pregnancy.
Perinatal morbidity was similar in pregnant women receiving antituberculous drugs
early during pregnancy to that in uninfected women. We conclude that TB
represents a risk factor for pregnancy. Early treatment of the disease during
gestation reverts its negative impact on perinatal outcome.
PMID- 9643637
TI - Recurrent chlamydial colonization during pregnancy.
AB - To evaluate the prevalence of and associated factors for recurrent Chlamydia
trachomatis infection in pregnant women, a retrospective cohort study was
conducted in an urban prenatal clinic in an underserved area. Women with
chlamydial carriage in pregnancy between 1992 and 1996 were identified by a
direct DNA assay. Entrance criteria limited the population to those who were
positive for chlamydia, were treated, had proof of cure and had at least one
subsequent test for chlamydia, all in the same pregnancy. Of the 149 women who
met entrance criteria, 25 (17%) had recurrent chlamydial carriage. The only
identified risk factor was maternal age <20 years (21 of 98 vs. 4 of 51, odds
ratio = 3.21). Infection with gonorrhea or other sexually transmitted diseases
during the same pregnancy were not predictive of reinfection. Initial therapy
with azithromycin, when compared to erythromycin, did not appear protective for
recurrent infection. Pregnant adolescents are more likely to have recurrent
chlamydial infection. Prenatal care programs should consider this when counseling
and treating these patients.
PMID- 9643638
TI - Gaucher's disease and pregnancy.
AB - Gaucher's disease is an autosomal recessive lysosomal storage disease, resulting
from a deficiency of the enzyme glucocerebrosidase, which is required for the
lysosomal degradation of glycolipids. The clinical manifestations of the disease
show a large heterogeneity, including hepatosplenomegaly, "bone crisis" and
fracture, anemia, thrombocytopenia and, in the rarest types II and III,
neurological decompensation. Type I, the most common form, usually presents with
less severe symptoms and at a more advanced age. More than 30 mutations within
the glucocerebrosidase gene have been recognized, and certain mutations seem to
be related with a particular phenotype expression of the disease. Modern
diagnosis of Gaucher's disease is performed by either determining the enzyme
activity in peripheral blood leukocytes or through DNA-based analysis. Pregnancy
concurrent with Gaucher's disease has several risks, including an increased
severity of anemia and thrombocytopenia that can potentiate postpartum bleeding,
and increased risk of infection and possibly an increased spontaneous abortion
rate. Nevertheless, the majority of these pregnancies seem to proceed to term
without significant complications. The effects that pregnancy might have on the
course of the disease are still unresolved. Enzyme replacement therapy with
alglucerase is the treatment of choice for patients with Gaucher's disease, but
it is yet to be shown whether alglucerase reduces the risk of these complications
during pregnancy and whether its use has any adverse effect on fetal development.
We present an extensive review of the current literature regarding Gaucher's
disease with special emphasis on pregnancies coexistent with this disease and, an
analysis of the genetics, relevant prenatal diagnostic issues, and current
treatment modalities.
PMID- 9643639
TI - Prenatal ultrasonographic diagnosis of fetal intracranial tumors: a review.
AB - Our objective was to review current literature pertaining to prenatal
ultrasonography of various fetal intracranial neoplastic and non-neoplastic
tumors. To this goal, all manuscripts published in the English language regarding
this topic obtained from a MEDLINE search from 1966 through January 1998 were
selected and reviewed. Additional sources were identified through cross
referencing. Intracranial fetal tumors are extremely rare and precise diagnosis
is dependent on histology examination of tissue obtained at subsequent surgery or
autopsy. Currently, prenatal ultrasonographic findings associated with the
following fetal intracranial tumors have been described: teratomas;
neuroepithelial tumors including: glioblastoma, astrocytoma, gangliocytoma,
medulloblastoma, choroid plexus, and papilloma; and mesenchymal tumors. Non
neoplastic fetal intracranial tumors are even less frequent and include:
unilateral megalencephaly, heterotopia, and lipoma of the corpus callosum.
Cardinal ultrasonographic findings associated with fetal intracranial tumors
include: echogenic and semicystic space occupying lesions with or without
distortion of normal symmetrical intracranial (usually midline) structures,
calcifications, craniomegaly, polyhydramnios, obstructive hydrocephaly, high
output cardiac failure (hydrops fetalis), the presence of other associated
structural anomalies, and infrequently abnormal cerebral Doppler flow
velocimetry.
PMID- 9643640
TI - Development of pulmonary lipophilic antioxidants and peroxidizable lipids during
lung maturation.
AB - The objective of this article is to test whether the concentration of potentially
oxidizable lipids (polyunsaturated fatty acids [PUFA], total and free
cholesterol) and lipophilic antioxidants (plasmalogens, vitamin E) in the fetal
lung correlate with lung maturation (P/S ratio). In amniotic fluid
palmitic/stearic acid (P/S) ratio, concentrations of PUFA, total and free
cholesterol, vitamin E, and plasmalogens were measured. Ratio of PUFA to stearic
acid (PUFA/S ratio) was determined in lung effluent of 15 preterm infants with
IRDS and compared with values from 15 term healthy infants. Concentrations of
plasmalogens, PUFA, total and free cholesterol increase significantly with
increasing P/S ratio. No correlation of vitamin E with lung maturation has been
found. The PUFA/S ratio is significantly lower in lung effluent of preterm (0.79
+/- 0.27) when compared with term infants (2.02 +/- 0.38). Our results suggest
that the higher susceptibility of preterm infants for oxidative lung injury is
not caused by an unfavorable ratio of oxidizable lipids to lipophilic
antioxidants in surfactant, but rather by a lower amount of PUFA containing
surfactant lipids. Our results are in accordance with data from Sosenko et al.
who have shown that high levels of PUFA in the rat lung have a protective effect
against oxygen-induced lung damage.
PMID- 9643641
TI - Uncomplicated baseline fetal tachycardia or bradycardia in postterm pregnancies
and perinatal outcome.
AB - OBJECTIVE: to assess perinatal outcome in post-term pregnancies in which fetal
heart rate (FHR) monitoring revealed either uncomplicated baseline fetal
tachycardia (> or = 160 bpm) or fetal bradycardia (< or = 120 bpm). STUDY DESIGN:
We performed a case-control study of patients who underwent fetal assessment
between July 1989 and June 1995, as part of post-term evaluation. Inclusion
criteria consisted of nonlaboring afebrile patients with singleton post-term
pregnancies > or = 41 weeks of gestation by strict dating criteria (last
menstrual period consistent with ultrasound biometric parameters obtained prior
to 20 weeks' gestation), normal fetal anatomy, intact membranes, and reactive
nonstress test with no evidence of chorioamnionitis. Patients with fetal tachy or
brady arrhythmias, FHR decelerations, or loss of short-term beat-to-beat
variability were excluded. Baseline FHR was recorded retrospectively by an
observer blinded to maternal and neonatal clinical outcome. For each case of
uncomplicated baseline fetal tachycardia (> or = 160 bpm) or bradycardia (< or =
120 bpm), either two or three control cases (matched for maternal age and
parity), with FHR > 120 bpm and < 160 bpm, were identified. Outcome variables
assessed included: incidence of cesarean delivery, nuchal cord at delivery,
meconium-stained amniotic fluid (AF), 5-min Apgar score < 7, fetal growth
restriction (< 10th percentile for 41 weeks' gestation), meconium aspiration
syndrome, and neonatal intensive care unit (NICU) admission. Statistical analysis
included two-tailed t-test and chi2 test when appropriate, with p < 0.05
considered significant throughout. RESULTS: During the study period 1390 post
term patients (6.81% of the general population) were assessed. Of these, 31
(2.23%) fetuses exhibited baseline FHR > or = 160 bpm, and 76 fetuses (5.46%)
exhibited baseline FHR < or = 120 bpm. No significant differences were noted in
the incidence of cesarean delivery, presence of nuchal cord at delivery, meconium
stained AF, 5-min Apgar scores < 7, fetal growth restriction, meconium aspiration
syndrome, or the incidence of NICU admissions between the groups of patients with
fetal tachycardia, bradycardia, and their respective controls. CONCLUSIONS:
Uncomplicated baseline fetal tachycardia or bradycardia in postterm patients are
not associated with an increase in the incidence of adverse perinatal outcome.
PMID- 9643642
TI - Prenatal diagnosis by chorionic villus sampling in multiple pregnancies prior to
fetal reduction.
AB - Ovulation induction and assisted-reproduction techniques have dramatically
increased the incidence of high-risk multiple pregnancies over the past 10 years.
Perinatal outcome may be improved by the use of multifetal reduction. The fetus
to be reduced used to be selected only on technical grounds. We report on the
results of prenatal diagnosis by chorionic villus sampling (CVS) during the first
trimester in 32 multifetal pregnancies in which fetal reduction was requested.
The mean gestational age at CVS was 10.5 weeks. Chromosomal analyses were
available for all sampled fetuses, three of which were chromosomally abnormal. In
24 couples, fetal reduction to twin pregnancies was successfully carried out
within 1 week after the CVS. In seven cases, the couples elected not to proceed
with fetal reduction after receiving information that the chromosomal analysis
was normal in all fetuses. Mean gestational ages at delivery were, respectively,
34.6 and 31.8 weeks in the reduced and the nonreduced groups (p = 0.04). No fetal
losses occurred in either group; one neonatal death was observed after a preterm
delivery because of preeclampsia in a twin pregnancy. Prenatal cytogenetic
diagnosis during the first trimester in multiple pregnancies prior to fetal
reduction appears to be feasible, accurate, and safe. Abnormal chromosomal
results indicate the fetus(es) to be reduced. The parents' decisions not to
proceed with the fetal reduction procedure, where chromosomal results in all the
fetuses were normal, were unexpected.
PMID- 9643643
TI - Temporal expression of elastic fiber components in bladder development.
AB - Fetal and postnatal bovine bladders were examined for expression of elastic fiber
components by immunohistochemistry as well as by measurement of steady state mRNA
levels. Expression of fibrillin-1, microfibril-associated glycoprotein (MAGP) and
elastin during the fetal period were compared with that of postnatal two year old
animals (heifers) and adults. Each bladder was separated into two distinct tissue
samples: 1) the outer smooth muscle layer (detrusor) and 2) the inner epithelium
(urothelium) lined lamina propria (urotherial-lamina propria). Each of these
samples was analyzed separately. Distribution of the elastic fiber components,
determined by immunohistochemistry with matrix-specific antibodies, was different
depending upon the region of the bladder wall examined and its developmental
stage. In particular, MAGP and fibrillin-1 were conspicuously present in the
urothelium during the later fetal stages. RNA products of elastic fiber genes
were detectable both in the detrusor smooth muscle and urothelial-lamina propria
fractions. The highest level of expression occurred in the urothelial-lamina
propria fraction during the late second-early third trimester. Elastin expression
was different from that of MAGP and fibrillin-1. The highest levels of steady
state elastin mRNA occurred at the earliest developmental stages examined and
then progressively decreased through term. A high level of elastin expression
occurred within the inner or lamina propria layer of the bladder. Since this
layer is the functional capacitance layer within the bladder, its flexibility is
likely related to the structural integration of elastin and associated
microfibrillar components.
PMID- 9643644
TI - The modification of alveolar bone proteoglycans by reactive oxygen species in
vitro.
AB - Reactive oxygen species (ROS) are being increasingly implicated in the connective
tissue degradation associated with chronic inflammatory conditions, such as
periodontal disease. The present study investigated the effects of ROS on the
proteoglycans (PG) of alveolar bone which are important structural components
within the periodontium. PG were isolated from ovine alveolar bone and exposed to
increasing concentrations of hydrogen peroxide (H2O2) or to a hydroxyl radical
(.OH) flux for 1 h or 24 h, and the degradation products examined for
depolymerisation and chemical modification of the PG structure. ROS were
demonstrated to be capable of degrading alveolar bone PG in vitro, the .OH
species resulting in greater modification than H2O2. The degradative effects
observed included cleavage of the protein core and depolymerisation of the GAG
chains. The core proteins were more susceptible to degradation than the GAG
chains in the presence of H2O2 alone, although both the core proteins and the GAG
chains were extensively degraded in the presence of a .OH flux for both 1 h and
24 h. Exposure of the PG to .OH for 24 h resulted in significant modification to
the amino acid composition with decreases in the proportion of leucine and the
complete loss of proline, tyrosine and phenylalanine evident. The results
highlight the potential role of ROS as an important mechanism in considering the
pathology of periodontal tissue destruction.
PMID- 9643645
TI - TGF-beta1 binding protein-like modules of fibrillin-1 and -2 mediate integrin
dependent cell adhesion.
AB - Human fibrillin, a major component of the extracellular matrix, exists as two
highly homologous forms (fibrillin-1 and -2). Several modules of fibrillin are
homologous to TGF-beta1 binding protein. Two of these modules, D25 (the 25th
module of fibrillin-1 and -2 D segment) and D12 (the 12th module of fibrillin-2 D
segment) contain the cell adhesion motif arginyl-glycyl-aspartyl (RGD). The
ability of RGD to mediate adhesion to D25-1 and D12-2 was investigated using
bacterially expressed fusion proteins. Human skin fibroblasts and murine L-cells
were used in microassays of cell attachment and cell spreading on fibrillin
fusion-protein substrata. Dose-dependent experiments and competitive inhibition
by soluble RGD-containing peptides demonstrated that D25-1 and D12-2 mediate RGD
dependent cell adhesion. These results provide evidence for a cell adhesion
function of fibrillin-2. Inhibition with anti-integrin antibodies showed that
alpha(v) and beta3 integrins mediate adhesion to D25-1, while alpha3, alpha(v)
and beta1 are involved in adhesion to D12-2. Binding of different receptors may
elicit distinct cell signalling supporting the hypothesis that fibrillin-1 and
fibrillin-2 have distinct roles.
PMID- 9643646
TI - Tubulointerstitial nephritis antigen (TIN-ag) is expressed in distinct segments
of the developing human nephron.
AB - Tubulointerstitial nephritis antigen (TIN-ag) is a 58 kDa glycoprotein restricted
within the kidney to basement membranes underlying the epithelium of Bowman's
capsule and proximal and distal tubules. Autoantibody formation against this
component has been described in association with primary immune-mediated
tubulointerstital nephritis, membranous nephropathy and anti-glomerular basement
membrane nephritis. In the present report, the ontogeny of this protein was
studied in human fetal kidney tissue by immunohistochemical analysis of immature
and developing nephrons using a panel of monoclonal and polyclonal antibodies.
TIN-ag is first detected in basement membranes underlying the epithelium of
Bowman's capsule of early capillary loop stage glomeruli and the primitive
proximal tubule. No detectable expression is observed in the basement membranes
of the branching ureteric bud, nephrogenic vesicle, or comma shape and s-shape
stages of nephrogenic development. Increased staining of the proximal tubular
basement membrane is associated with outgrowth of the primitive tubule from the
urinary pole of the developing glomerulus. In more mature fetal tubules, TIN-ag
expression closely resembles that of previously reported observations in mature
tissue where it is present in high amounts in the basement membranes of proximal
tubules, and to a lesser extent in Bowman's capsule and distal tubules. Our
results suggest that TIN-ag expression is developmentally regulated in a precise
spatial and temporal pattern throughout nephrogenesis.
PMID- 9643647
TI - Reduction in basic fibroblast growth factor mediated angiogenesis in vivo by
linomide.
AB - Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxoquinoline-3-carboxa
mide) is a novel immunomodulator with a potent anti-tumoral activity. This study
was undertaken to test the effect of Linomide on basic fibroblast growth factor
(bFGF) induced angiogenesis in vivo, which manifests itself in an increased
number of blood vessels per unit of cell infiltrated area. Subcutaneously
implanted polyvinyl alcohol sponges (PVS) in guinea pigs were used as a model
system to quantitate angiogenesis in vivo. Oral treatment with Linomide was able
to reduce significantly the bFGF induced blood vessel growth and proliferation
within the implanted PVS, relative to untreated controls. In addition, Linomide
significantly reduced the bFGF mediated augmentation of protein and collagen
content in the implanted PVS, indicating an inhibition in the deposition of
extracellular matrix (ECM). We conclude that the potent inhibition of bFGF
induced angiogenesis by Linomide in vivo in addition to immunomodulatory effects
may have potentially important clinical applications.
PMID- 9643648
TI - The influence of inflammation-mediated osteopenia (IMO) on the structure of
rabbit bone and skin collagen fibrils.
AB - The influence of Inflammation Mediated Osteopenia (IMO) on rabbit skin and bone
(trabecular and cortical) collagen fibrils was studied by electron microscopy.
Severe abnormalities in collagen fibril structure were detected, at the
ultrastructural level, in skin and bone specimens from IMO rabbits. In treated
animals the arrangement of fibrils is anarchic. The overall collagen fibril
architecture is disturbed compared to normal. IMO collagen fibrils' mean diameter
values were significantly larger than those from controls, in all examined
tissues. However, the banding patterns of fibrils were normal in all cases.
Computer analysis shows no differences in charged amino acid composition between
IMO and untreated samples. Our results show a correlation between the effects
induced by osteopenia on skin and bone collagen.
PMID- 9643649
TI - A contribution to the regulation of proteoglycan production: modulation by TGF
alpha, TGF beta and IL-1 of glycosaminoglycan biosynthesis on beta-D-xyloside in
chick embryo fibroblasts.
AB - In order to elucidate the mechanisms determining the variability in the
proteoglycan structure and the factors involved in this determination, we treated
chick embryo skin fibroblasts with beta-D-xyloside to obtain glycosaminoglycan
chains deprived of core proteins, and with different cytokines (transforming
growth factor alpha and beta, interleukin-1) to produce variability. The
different cytokines specifically regulate both cellular and extracellular amount
and composition of glycosaminoglycans. Beta-D-xyloside treatment does not change
protein content and protein synthesis, whereas it increases overall extracellular
sulphated glycosaminoglycan production, heparan sulphate and chondroitin sulphate
content, and reduces that of dermatan sulphate. This indicates that the core
protein regulates quantitative proteoglycan production, and probably directs
(with appropriate signals) the core oligosaccharide bound to it to the right
synthesizing enzymes. The modulatory action of the different cytokines on
sulphated glycosaminoglycan production and classes remains, even though the core
protein is absent. This indicates that the cytokines also act on the
glycosyltransferases. Our results suggest that the proteoglycan production may be
subject to a double control, one of which is at the level of the core protein and
the other, mediated by environmental signals, at the level of glycosaminoglycan
synthesizing enzymes.
PMID- 9643650
TI - Heparin sensitive and resistant vascular smooth muscle cells: biology and role in
restenosis.
AB - Vascular smooth muscle cells (VSMC)s are characterized by their acute growth
inhibition by heparin and heparan sulfates; however, recently the isolation of
VSMCs which display greatly diminished sensitivity to the antiproliferative
action of heparin have been reported. These heparin resistant (HR) VSMCs have
been derived through multiple passage of normal rat VSMCs in culture media
containing high heparin doses, by transformation of VSMCs with oncogene
containing vectors, or have been isolated from vascular tissues of spontaneously
hypertensive rats, healthy humans, or humans with restenosis where their presence
is not limited to sites of injury. Initial characterizations of HR VSMCs are
reviewed, and here we propose a definition of HR VSMCs. To date the mechanisms
underlying heparin insensitivity remain elusive. Further study of HR VSMCs may
expand our understanding of cell growth regulation by heparin, establish whether
HR VSMCs contribute to the reported failure of heparin to combat restenosis in
humans, and identify cellular mechanisms driving certain vascular proliferative
diseases.
PMID- 9643651
TI - Hsp47 binds to the KDEL receptor and cell surface expression is modulated by
cytoplasmic and endosomal pH.
AB - Hsp47 is a novel glycoprotein that binds specifically to procollagen and is
retained in the ER by its COOH-terminus RDEL peptide sequence (Satoh, M. et al.
Jol. Cell Biol. 1996; 133: 469-83). In this paper, we report that erd2P, the KDEL
receptor, is distributed, coprecipitates with, and binds to Hsp47. Also, under
stress conditions and lowering of pHi, the cytoplasmic epitope of erd2P is not
recognized by erd2P antibodies unless the cells are pretreated with NEM.
Coincident with the masking of the cytoplasmic epitope of erd2P, following
lowering of pHi, Hsp47 is not retained but eludes its retention receptor to be
expressed on the cell surface. Alkalization of the endosomal compartments by
treatment with NH4Cl or chloroquine also results in the loss of Hsp47 to the cell
surface, presumably by inhibiting the retrieval of trans-Golgi network proteins
from the cell surface. The expression of Hsp47 on the cell surface under
conditions of stress and alteration of pHi and pHe posture Hsp47 as a serpin
family protein that may modulate cell migration during development and invasion
and metastasis in cancer.
PMID- 9643652
TI - Mechanical role of elastin-associated microfibrils in pig aortic elastic tissue.
AB - The contribution of microfibrils to the mechanical performance of the meshwork of
elastic tissue in mature pig aorta was investigated by comparing the properties
of autoclaved tissue containing elastin and microfibrils with autoclaved tissue
that had been treated with dithiothreitol (DTT) or hot alkali to remove the
microfibrils from the elastin. The uniaxial tensile stress-strain curve of the
autoclaved tissue was linear to a strain of 0.6 or 0.7 and increased nonlinearly
up to the breaking strain. The nonlinearity at high strains could not be
accounted for by nonGaussian behavior and was attributed to the progressive
alignment of the elastic fibers with strain. Removal of the microfibrils with DTT
or treatment with calcium reduced the modulus at low strains by 12% and 4%
respectively and increased the modulus at high strains, suggesting that the
microfibrils have the capacity to change the orientation of the elastin fibers,
possibly transmitting some of the load from one elastin fiber to another. Our
findings suggest two possible roles for the microfibrils in vivo: distributing
the load throughout the elastic fibers of the arterial wall and direct load
bearing. The modulus and the breaking stress of the rings decreased linearly with
the duration of alkali treatment starting immediately. By 45 min the modulus had
dropped by 30% and the breaking stress by 50%, even though the amino acid content
of the extract gave little evidence of elastin hydrolysis. Alkali treatment
should not be used on autoclaved pig aortic tissue to be used for mechanical
testing.
PMID- 9643653
TI - Identification and localization of type IV collagen chains in the inner ear
cochlea.
AB - Mutations in the genes encoding the alpha3(IV), alpha4(IV) and alpha5(IV) chains
of type IV collagen have been implicated in the pathogenesis of Alport's
syndrome, a hereditary disorder characterized by progressive nephropathy and
sensorineural deafness. The known expression of these chains in kidney basement
membranes supports the contention that they play a crucial role in the
ultrafiltration function. Whether they play a role in auditory signal
transduction remains unknown as heretofore, they have not been identified in the
inner ear. In the present study, the expression of type IV collagen in cochlea of
the inner ear of guinea pigs was determined. All six alpha-chains of type IV
collagen were identified by biochemical and immunological methods. By indirect
immunofluorescence, alpha1(IV) and alpha2(IV) chains were localized to the spiral
limbus, basilar membrane and tectorial membrane. The alpha3(IV), alpha4(IV),
alpha5(IV) and alpha6(IV) chains localized exclusively to the tectorial membrane
and basilar membrane. These results suggest a possible role of type IV collagen
chains in the active tuning of the basilar and tectorial membrane, an essential
step in frequency discrimination and amplification of auditory signals.
PMID- 9643654
TI - Autonomic innervation of the bovine testis.
AB - The autonomic nerve supply of the bovine testis is investigated in animals of
different ages by means of immunohistochemistry. Staining with antiserum to
protein gene product 9.5 gives the most complete results for the study of the
general innervation pattern. Autonomic nerves reach the testis by three different
routes: with the blood vessels of the spermatic cord (funicular nervous
contribution), by the mesorchium (mesorchial nervous contribution) and by the
ligamentous bridge between epididymal tail and testis (caudal nervous
contribution). The vessels of the spermatic cord are densely innervated. The
large vessels of the vascular layer within the tunica albuginea display a
discontinuous innervation pattern. In the interior of the testis, the caudal half
of the gonad is completely free of any innervation. Slight differences in
arrangement and fiber composition of testicular nerves in calves and bulls point
to a reduction of the innervation with advancing age. The vast majority of bovine
testicular nerves are dopamine-beta-hydroxylase-positive postganglionic
sympathetic axons with vasomotor function. There is no evidence for a cholinergic
innervation of the bovine testis. About half of the bovine testicular nerves are
neuropeptide Y-immunoreactive. In the adult, solitary calcitonin gene-related
peptide-immunoreactive fibers are the only ones independent of blood vessels. The
absence of an innervation in the caudal half of the testis underlines the
importance of local factors and blood-borne substances for the regulation of
intratesticular blood flow in the bovine.
PMID- 9643655
TI - Corticosterone induces hypoactivity of prolactin-immunoreactive cells.
AB - In order to determine whether corticosterone regulates activity of rat
lactotrophs by acting directly at the pituitary level, immunohistochemical
studies were carried out in adrenalectomized rats, subjected or not to treatment
with corticosterone or colchicine, and in monolayer cultures after incubation
with corticosterone. Adrenalectomy increased cellular and nuclear areas (p<0.01)
of prolactin-immunoreactive cells without affecting their cytoplasmic area.
Similar results were found in adrenalectomized and colchicine-treated animals.
Corticosterone reversed the effects of adrenalectomy, although normal values were
partially reversed. In cultured pituitary cells, exposure to corticosterone
reduced numerical density and cellular, cytoplasmic and nuclear areas with
respect to control dishes. Morphological differences in shape, arrangement and
nuclear features were observed after treatment with corticosterone. These results
demonstrate an inhibitory effect of corticosterone on the activity of rat
pituitary prolactin cells and suggest that corticosterone induces hypoactivity by
acting on the pituitary prolactin cells of male rats.
PMID- 9643656
TI - Organization of the hypobranchial motor column of the clearnose skate, Raja
eglanteria, with comparisons to tetrapods.
AB - Motoneurons that supply the clearnose skate's hypobranchial musculature, via the
occipital nerve and first seven ventral spinal nerve roots, are located within a
column that extends from a level just caudal to the obex through the
corresponding rostral spinal cord segments. Individual muscle motoneuron pools
within the column are considerably intermingled and overlap. Comparisons with
tetrapods, particularly mammals, where the hypobranchial musculature is greatly
modified, reveal general conserved features. The motor column's multisegmental
organization is retained although, in mammals, the column begins rostrally at
medullary levels, where hypobranchial muscle motoneurons are intimately
associated with motoneurons to lingual muscles, and it is restricted caudally to
fewer spinal cord segments. In addition, despite an intermingling of motoneurons
that supply individual hypobranchial muscles there is a shared rostrocaudal
sequence of the motor pools. Rostral most hypobranchial motoneurons supply the
most ventral and anterior muscles (i.e., m. coracomandibularis, and likely m.
coracohyoideus, of skate and the suprahyoid musculature, m. geniohyoideus, of
tetrapods). Caudal hypobranchial motoneurons supply the skate's mm.
coracohyomandibularis, coracoarcualis communis and coracobranchialis and the
tetrapod's entire infrahyoid muscle complex. The intermingling of multisegmental
motoneuron populations innervating different hypobranchial muscles might be
attributed to intermixing of premuscle mesoderm derived from several postotic
somites but the musculotopic organization along the rostrocaudal axis indicates
that pre- and posthyoid muscle mesoderm may partially keep its identity during
its migration to the floor of the pharynx and oral cavity.
PMID- 9643657
TI - Microvascularization in trigeminal ganglion of the common tree shrew (Tupaia
glis).
AB - Since there is only a limited number of studies of the blood supply to the
trigeminal ganglion (TG) in mammalian species, the TG from 16 common tree shrews
(Tupaia glis) were investigated by light microscope, transmission electron
microscope (TEM) and the corrosion cast technique in conjunction with scanning
electron microscope (SEM). It was found that the TG contained clusters of neurons
in the peripheral region whereas the bundles of nerve fibers were located more
centrally. Each ganglionic neuron had a concentric nucleus and was ensheathed by
satellite cells. It was noted that blood vessels of a continuous type were
predominantly found in the area where the neurons were densely located and were
much less frequently observed in the area occupied by nerve fibers. With TEM, the
TG was shown to be mainly associated with large neurons containing big nuclei and
prominent nucleoli. The blood supply of the TG is derived from the most rostral
branch of the pontine artery, from the stapedial artery or sometimes from the
supraorbital artery, and from the accessory meningeal artery which is a branch of
the maxillary artery passing through the foramen ovale. These arteries give off
branches and become capillary networks in the ganglion before draining blood to
the peripheral region. The veins at the medial border drained into the cavernous
sinus directly or through the inferior hypophyseal vein, while those at the
lateral side of the ganglion carried the blood into the pterygoid plexus via an
accessory meningeal vein. The veins along the trigeminal nerve root joined the
posterior part of the cavernous sinus. These studies establish a unique
anatomical distribution of the TG blood supply in the tree shrew and the utility
of the cast/SEM technique in discerning detailed features of the blood supply in
the nervous system.
PMID- 9643658
TI - Morphology of holes in aponeuroses as caused by perforating nerves or vessels at
the medial epicondyle of the elbow.
AB - In the present paper the morphology of holes in aponeuroses of origin of muscles
is generally modelled. These holes result from perforations of the aponeuroses by
nerves or vessels, or from joints which are crossed by the line of origin of the
aponeurosis. The concept of aponeurotic holes as morphological entities
comprehensively explains frequent small-scale anatomic variations in muscles,
such as muscles with multiple separate origins in parallel. It also contributes
to a better understanding of nerve compressions and their surgical treatment. The
model is illustrated by dissection results of the aponeuroses at the medial
epicondyle of the elbow, which are typically perforated by the n. medianus, the
a. brachialis, and the n. ulnaris.
PMID- 9643659
TI - Congenital tibial aplasia with preaxial polydactyly. A case report.
AB - An anatomical study of a left lower limb with congenital tibial aplasia and
preaxial polydactyly amputated at 10 months of age was carried out. The tibia was
replaced by a fibrous band (a band of connective tissue) and there were four
cuneiforms, six metatarsal bones and seven toes. The second metatarsal bone
showed characteristics of the hallux. An intermuscular septum which showed an
orifice for the anterior tibial artery was found on the medial side of the leg
and foot. All the muscles of the leg and foot were present except for the
tibialis posterior muscle, which was replaced by two atypical muscles. No
muscular attachments reached the fibrous band. Several intertendinous connection
bands were found. Also, an accessory muscular belly split from the tibialis
anterior tendon and attached to the common flexor tendinous sheet of the foot. An
unusual motor branch of the deep peroneal nerve ran together with this belly to
supply the intrinsic muscles of the hallux. We also observed other minor
anomalies of the nerve pattern. The arterial pattern was complete, except for
some arteries which showed both an anomalous origin and course. The findings of
this study suggest that the development of the skeletal elements plays an
important role in the differentiation of the muscles, tendons, arteries and
nerves. We postulate that a dysmorphogenic event involving the development of the
tibial field of the limb could give rise to both defective histodifferentiation
of the tibia and defective programmed cell death in the pre-hallucial anlage.
These anomalies would determine secondary adaptations of muscles, tendons,
vessels and nerves of the limb.
PMID- 9643660
TI - A generic morphological model of the anatomic variability in the m. flexor
digitorum profundus, m. flexor pollicis longus and mm. lumbricales complex.
AB - In the present study a generic model is presented of the anatomic variability in
the muscle group formed by the m. flexor digitorum profundus, m. flexor pollicis
longus and mm. lumbricales. This model provides a hypothesis about the structural
causes of the frequent interdependence of tendons and muscle bellies in this
muscle group. The model considers the muscle group as composed of two simple
elementary building blocks: the monogastric contractile units of the FDP-FPL, and
the digastric contractile elements of the lumbrical, and shows that these units
can be assembled into complex entities, to which in reality a third structural
element, the synovial membranes, not discussed in the present paper, adds a
further complexity. The model allows to generate homologues of the existing
anatomical variants, which are illustrated by typical dissection results. The
present study should be of relevance to the morphologist, embryologist, surgeon,
and musician/pedagogue. To the morphologist, it presents an alternative method of
description or understanding of anatomic variability, based on (i) the 'atomary'
concept that the anatomic structure is assembled from simple basic elements, and
(ii) the local spatial constraints. To the embryologist, it raises the question
to what degree the 'atomary' anatomical components of this model, which describes
the macroscopic anatomy of the muscle group in detail, have an embryological
basis. To the surgeon, the study presents detailed information about the scope of
the variability in the deep flexor group, and the nature of its intertendinous
connections. To the musician/pedagogue, it presents a visual illustration of the
congenital interdependence of the muscles and tendons of an important finger
motor group, as a possible cause of lack in finger independence which may hamper
a fluent instrumental technique.
PMID- 9643661
TI - Diagnosis and management of seminal vesicle cysts associated with ipsilateral
renal agenesis: a pooled analysis of 52 cases.
AB - OBJECTIVE: Seminal vesicle cysts combined with ipsilateral renal agenesis
represent a rare urological anomaly. We searched the literature to review the
clinical presentation, diagnosis and therapeutic treatment options of this
anomaly. METHODS: A pooled analysis was performed of 52 cases of seminal vesicle
cysts combined with ipsilateral renal agenesis, including our own observation.
The evaluation included: patient age at diagnosis, race, laterality (R/L),
presence of ureteral remnant in the cyst, presenting symptoms, diagnostic
examinations, treatment and outcome. RESULTS: The mean age at diagnosis was 30.2
years. The majority presented in the 2nd, 3rd and 4th decade of their lives. Only
2 patients (4%) were of African origin, all others were Caucasians. The
distribution R:L was 2:1. Ureteral remnants were present in 14 patients (27%).
The most common symptoms were: dysuria (37%), frequency (33%), perineal pain
(29%), epididymitis (27%), pain following ejaculation (21%) and scrotal pain
(13%). Infertility was found in 9 patients (17%). The cyst was palpable by
digital rectal examination in 79%. All patients underwent intravenous urography,
and 88% underwent cystoscopy. Other frequently performed investigations are:
ultrasonography (27%), CT scanning (27%), vasovesiculography (46%) and
urethrocystography (23%). The final treatment was open surgery in 74%, aspiration
in 6%, transurethral deroofing of the cyst in 6% and spontaneous rupture in 4%.
In 6% no treatment was given and in 4% the treatment is unknown. All patients
were free of symptoms after open exploration. The success rates after
transurethral deroofing and aspiration were 75 and 30% respectively. CONCLUSION:
Seminal vesicle cysts combined with ipsilateral renal agenesis are a rare
urological anomaly, occurring in men in the 2nd to 4th decade of their life. They
present with symptoms of bladder irritation and obstruction and with pain in the
perineum and scrotum. Epididymitis is frequently found. The diagnostic work-up
consists of a digital rectal examination, transrectal and abdominal
ultrasonography, CT scan and a cystoscopy. Open surgery and transurethral
deroofing of the cyst give excellent results (100 and 75% cure respectively).
Aspiration of the cyst should only be used for diagnostic purposes.
PMID- 9643662
TI - Gravity cavernosometry and assessment of complete smooth muscle relaxation:
helpful in the differential diagnosis of cavernous leakage?
AB - OBJECTIVE: To establish whether the relationship between cavernosal pressures and
gravitational pressures of infused liquid during gravity cavernosometry is linear
when complete smooth muscle relaxation is achieved and whether the determination
of this relationship could be helpful in the differential diagnosis between
organic and functional cavernous leakage. METHODS: Gravity cavernosometry was
performed in 50 impotent patients. The cavernosal pressure was measured at at
least four different gravitational pressures of the infused liquid. RESULTS: A
linear relationship was obtained in all patients with normal maximal cavernosal
pressure at gravity cavernosometry. A flat or nonlinear relationship was found in
those with abnormal maximal pressure, whatever the cause of cavernous leakage.
CONCLUSIONS: A linear relationship between cavernosal and gravitational pressures
characterizes complete smooth muscle relaxation during gravity cavernosometry.
However, the usefulness of the determination of this relationship is not yet
established.
PMID- 9643663
TI - A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus
castration in the treatment of metastatic and locally advanced prostate cancer.
AB - OBJECTIVES: To evaluate the efficacy and tolerability of 'Casodex' monotherapy
(150 mg daily) for metastatic and locally advanced prostate cancer. METHODS: A
total of 1,453 patients with either confirmed metastatic disease (M1), or T3/T4
non-metastatic disease with elevated prostate-specific antigen (M0) were
recruited into one of two identical, multicentre, randomised studies to compare
'Casodex' 150 mg/day with castration. The protocols allowed for combined
analysis. RESULTS: At a median follow-up period of approximately 100 weeks for
both studies, 'Casodex' 150 mg was found to be less effective than castration in
patients with metastatic disease (M1) at entry (hazard ratio of 1.30 for time to
death) with a difference in median survival of 6 weeks. In symptomatic M1
patients, 'Casodex' was associated with a statistically significant improvement
in subjective response (70%) compared with castration (58%). Analysis of a
validated quality-of-life questionnaire proved an advantage for 'Casodex' in
sexual interest and physical capacity. 'Casodex' had a substantially lower
incidence of hot flushes compared to castration (6-13% compared with 39-44%) and
the most commonly reported adverse events were those expected for a potent
antiandrogen. However, in patients with M0 disease at entry, the data are still
immature with only 13% of M0 patients having died. An initial analysis of this
immature data has suggested that the results in these patients may be different
to those obtained in patients with M1 disease. A further survival analysis in
patients with M0 disease is therefore planned when the data are more mature.
CONCLUSIONS: 'Casodex' 150 mg is less effective than castration in patients with
M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life
and subjective response when compared to castration and has an acceptable
tolerability profile. Thus 'Casodex' 150 mg monotherapy is an option for patients
with M1 prostate cancer for whom surgical or medical castration is not indicated
or is not acceptable.
PMID- 9643664
TI - Primary bladder carcinoma in situ: assessment of early BCG response as a
prognostic factor.
AB - OBJECTIVES: To evaluate the prognosis of primary bladder carcinoma in situ (CIS)
according to the response to bacillus Calmette-Guerin (BCG). PATIENTS AND
METHODS: Twenty-six cases of primary CIS were treated with BCG. Mean, median and
minimum follow-up periods were 47, 56 and 24 months. At 6 months, the patients
were evaluated endoscopically and the response was classified as complete,
partial or failure. RESULTS: Twenty-one patients (80.8%) showed complete response
to BCG, 3 did so after a second course; 28.5% relapsed or progressed at a mean of
44 months. Five patients (19.2%) did not respond initially and all progressed in
a period of 6 months. Early response to BCG was the only significant prognostic
factor (p < 0.005). CONCLUSIONS: A high- and a low-risk group of bladder CIS can
be differentiated according to the response to BCG. CIS of the bladder has a poor
prognosis, and the number of patients who developed progressive disease is
significantly higher among the nonresponders.
PMID- 9643665
TI - Significance of bladder neck involvement on progression in superficial bladder
cancer.
AB - OBJECTIVES: To determine the significance of bladder neck involvement in
predicting disease progression in superficial (stage Ta and T1) transitional cell
carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: A series of 277
patients with newly diagnosed superficial TCCs of the bladder was reviewed, and
disease progression (to T2 or worse) was considered. The significance of several
risk factors including bladder neck involvement was assessed in univariate and
multivariate analysis. RESULTS: Progression occurred in 28 (10.1%) of 277
patients during a median follow-up period of 7.7 years. Nineteen died of bladder
cancer. The following variables were found to be statistically significant at the
univariate analysis (p < 0.05): irritative symptoms, urine cytology, tumor stage,
involvement of the bladder neck, and tumor grade. Indeed, only involvement of the
bladder neck, tumor stage, and grade retained their value as independent factors
for progression at multivariate analysis. Patients were divided into three groups
according to the number of independent risk factors they had. Groups having none,
one, and two or three risk factors included 129, 99, and 49 patients with 5-year
progression rates of 0.8, 4.6 and 27.5%, and 15-year rates of 4.0, 20.1 and
42.7%, respectively. CONCLUSION: Involvement of the bladder neck is a significant
and independent risk factor for progression of superficial TCCs in addition to
the histologic grade and stage. The combination of these three risk factors
offers better prediction of progression in an individual patient.
PMID- 9643666
TI - Implantable microballoons: an attractive alternative in the management of
intrinsic sphincter deficiency.
AB - PURPOSE: All current bulking agents employed for treating stress urinary
incontinence (SUI) have significant limitations due to various side effects,
technical difficulties and inadequate long-term results. Implantable
microballoons were therefore tested as a new therapeutic modality for female
urinary incontinence. MATERIAL AND METHODS: The microballoons are implanted with
a new system which consists of the self-detachable cross-linked silicone balloon,
biocompatible filler material and a delivery system. Nineteen female patients
(mean age 63.3 years) with SUI grade 1 or 2 were studied prospectively. Using the
Blaivas-Olsson classification, 6 patients had stress incontinence type I, 4 had
type II and 9 had type III. Three to seven balloons (mean 4.2) were implanted per
patient. Patients were followed up with pad tests (g) and determination of leak
point pressure (LPP; cm H2O) and maximal urethral closing pressure (Pura max; cm
H2O) at 1, 3, 6, 12 and 18 months. RESULTS: The biocompatibility of the
microballoons was excellent. No significant adverse events were associated with
the procedure. With a mean follow-up of 14.4 months (range 10-18) 42.1% (8/19) of
the women are dry. In the latter the pad test improved from a preoperative mean
of 22.6 g (2-75) to 0 and the LPP increased from a preoperative mean of 38.5 cm
H2O (25-60) to 80.5 cm H2O (68-106). 36.8% (7/19) of the patients showed
significant improvement of their incontinence. In this group the pad test
improved from a preoperative mean of 39.1 g (8-112) to 9.7 g (2-29) and LPP from
a mean of 37.1 cm H2O (25-50) to 42.0 cm H2O (30-58). In 4 patients (21.05%) the
technique failed. Seven of the 8 cured patients had type III incontinence; the
eighth patient had type I incontinence. It failed in all patients with type II
incontinence. CONCLUSION: The implantation of microballoons is a safe, well
tolerated and clinically effective modality for the treatment of type III SUI,
i.e. intrinsic sphincter deficiency.
PMID- 9643667
TI - Long-term results following transurethral resection of the prostate.
AB - Two subsets of a single-center study population with benign prostatic hyperplasia
(n(1) = 232; n(2) = 214) undergoing transurethral resection (TUR) of the prostate
(TURP 1979 and 1995) entered a retrospective study designed to examine the long
term follow-up. The actual data were assessed with a patient-addressed
questionnaire. Preoperative voiding patterns did not differ significantly;
postoperative micturition revealed comparable results for both groups. Mortality
and TUR syndrome rates were reduced to very low levels. The most significant
improvement was found in blood transfusions. The postoperative incidence of
urethral stricture (1.7 vs. 1.5%) or bladder neck contracture (2.7 vs. 2.4%) were
low and did not alter significantly. Urinary incontinence changed for both
collectives (11.4 vs. 3.3%). Urodynamic investigations revealed that all (n = 21)
but 1 of the patients with TURP 1979 had the incontinence due to different
bladder dysfunctions, but not because of postoperative stress incontinence. The
questionnaire about the patient's actual contentment after TURP 1979 showed 79%
of the patients still satisfied, 12% neutral and 9% dissatisfied with their
micturition. Overall the patients reported a generally favorable view of TURP
outcome in the long-term follow-up.
PMID- 9643668
TI - A double-blind comparison of terazosin and tamsulosin on their differential
effects on ambulatory blood pressure and nocturnal orthostatic stress testing.
AB - OBJECTIVES: This single-centre, double-blind, randomized parallel-group study
compared ambulatory blood pressure (AMBP) and heart rate (HR) profiles and
responses to orthostatic testing (OT) for recommended regimens of tamsulosin
(TAM, modified release formulation) and terazosin (TER), two alpha1-adrenoceptor
antagonists that differ in their selectivity for alpha1-adrenoceptor subtypes,
pharmacokinetic properties and recommended posology for the treatment of lower
urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO).
METHODS: 50 elderly normotensive male volunteers (mean age 68 years, range 61-78;
27 had LUTS) entered a single-blind 24-hour placebo run-in followed by a 15-day
double-blind treatment in which the TER group received a 1-week treatment with 1
mg, then 1 week with 2 mg and finally a last dose of 5 mg, each dose administered
once daily in the evening, while TAM subjects received 0.4 mg once daily after
breakfast throughout. Subjects had AMBPs and OT while hospitalized on four
occasions: during the placebo run-in and subsequent to the first dose of 1, 2 and
5 mg TER or at corresponding times under TAM. Regular OT (blood pressure after 5
min supine and after 2 min standing) was carried out between 6:00 and 6:30 a.m.;
'nocturial' OT took place whenever the subject had to leave the bed at night to
void. RESULTS: The baseline blood pressure values were slightly higher in the TAM
group, but under treatment there was little difference between the treatments
with regard to circadian changes in AMBP and HR. Under TER, there were 10
incidents of symptomatic hypotensive OT in 9 subjects (2 with syncope);
furthermore, there were 24 events of asymptomatic exaggerated (> or = 20 mm Hg)
decrease in systolic blood pressure in 12 subjects. With TAM in contrast, there
was only 1 subject who experienced symptomatic hypotensive OT on 3 occasions
(this subject had a previous history of vertigo and ought not to have been
included); 7 subjects on TAM showed 16 incidents of asymptomatic hypotensive OT.
The difference between TER and TAM was statistically significant for the number
of subjects with positive symptomatic OT (p = 0.011). CONCLUSION: Once-daily
dosing of TAM after breakfast at a fixed dose level (0.4 mg) offers a more
efficient protection against undesired cardiovascular extension effects in the
normotensive elderly treated for LUTS suggestive of BPO than the usually
recommended treatment schedule of TER with step-up doses (1-5 mg) administered at
night.
PMID- 9643669
TI - Nephrectomy: A comparative study between the transperitoneal and retroperitoneal
laparoscopic versus the open approach.
AB - OBJECTIVES: Different techniques have been introduced to perform laparoscopic
nephrectomy using either the transperitoneal or the retroperitoneal route.
However, to date only few data exist comparing the results and morbidity of these
procedures as well as with the standard technique of open nephrectomy. MATERIAL
AND METHODS: This paper compares the clinical results of 18 transperitoneal
laparoscopic nephrectomies (TLN) for benign renal disease with 17 retroperitoneal
laparoscopic nephrectomies (RLN) and 19 consecutive open nephrectomies (Nx). All
groups were comparable in terms of indication. The analysis of clinical data
included operative time, morbidity, length of analgesic use and postoperative
hospital stay. RESULTS: The mean operative time for benign disease was 206.5 for
TLN, 211.2 for RLN and 117 min for open nephrectomy. Analgesic medication
requirement per patient was 2 days for TLN, 1 day for RLN and 4 days for Nx while
the postoperative hospital stay averaged 7 days for TLN, 6 days for RLN and 10
days for Nx. The time of convalescence was 21 days after RLN, 24 days after TLN
versus 40 days after open nephrectomy. CONCLUSIONS: Our results demonstrate an
overall clear advantage of a laparoscopic approach when compared to open surgery
and also reveals distinct benefits of a retroperitoneal approach.
PMID- 9643670
TI - Results of fibrin glue application therapy in testicular hydrocele.
AB - Nine patients, mean age 55 years, with testicular hydroceles, were treated by
aspiration and two-component fibrin glue injection. One patient was treated
twice. The glue contains 70-110 mg fibrinogen and 500 IU human thrombin in 0.5-
and 2-ml injections, respectively (Tisseel duo quick, Immune AB). The smaller
glue volume was used in 4 cases and the larger volume in 6 cases. The average
volume of hydrocele fluid was 77 (range 60-120) ml. Treatment caused no pain or
discomfort other than puncture of the skin and no pain-relieving medication was
required afterwards. In this series there were no infections but one
conservatively treated hematoma. The hydrocele of that patient disappeared.
Although the hydroceles recurred in 9 cases during the mean follow-up of 3.5
months, in 2 patients the hydroceles were clinically smaller than the original
one and symptoms were milder subjectively. Our findings suggest that fibrin
adhesive glue is not sufficiently effective in treatment of testicular
hydroceles.
PMID- 9643671
TI - Bladder washout and stone formation in paediatric enterocystoplasty.
AB - OBJECTIVE: To review the incidence of stone formation in our patients with
enterocystoplasty to determine the effect of regular bladder washout. METHODS:
From 1988 to 1995, a prospective cohort of 30 children underwent enteroplasty
with continent diversion. Over the same period, a consecutive group of 30
children had an augmentation alone. All were instructed to wash out their bladder
on a weekly basis with sterile water. The frequency of the washouts increased if
there were problems with increasing mucus production. Their incidence of stone
formation has been compared to a similar group of 30 children performing clean
intermittent self catheterisation (CISC) on their native bladders. RESULTS: Five
(17%) children with continent diversions formed bladder stones (mean time to
formation 35 months, range 13-59 months) were compared with 2 (7%) of children
with augmentation. No child performing CISC alone formed stones. CONCLUSIONS: A
regime of regular bladder washout in children with enterocystoplasty did not
significantly reduce the incidence of stone formation when compared to previously
published data.
PMID- 9643672
TI - Culture of human urothelial cells on a cell-free dermis for autotransplantation.
AB - OBJECTIVE: Techniques for in vitro culturing and autotransplantation have been
developed for a variety of human cells and are used today in several fields of
medicine. In reconstructive surgery within the genitourinary tract, autologous
urothelial cells cultured in vitro could be of considerable value but have not
yet been used clinically. The aim of this study was to facilitate transplantation
of cultured urothelium by establishing a reliable method for culturing urothel on
an immunologically inert and biodegradable structure. METHODS: Normal human
urothelial cells were cultured in vitro using a feeder-cell system. To achieve an
optimal carrier structure, cells were removed enzymatically from a split
thickness skin graft. Human urothelial cells were then seeded on the cell-free
dermis and incubated in vitro. The seeded dermis samples were investigated
histologically and with immunohistochemical methods at days 7, 14 and 21.
RESULTS: The human urothelial cells incubated in vitro reached confluence after 7
10 days and the cells could be cultured through 9 passages with preserved
proliferative potential. When the cells were seeded on a cell-free dermis they
attached, formed colonies and became confluent and stratified up to three cell
layers after 21 days of incubation. The urothelial origin of the cells was
confirmed by immunohistochemical staining against cytokeratin. CONCLUSION: The
advantages of culturing the urothelial cells on a cell-free dermis include a
short time lag until grafts are available, probably facilitated transplantation
procedure, transplantation of undifferentiated cells and the formation of a
vascularised base under the new urothelium. The method described in this study
may be of great value in providing autologous urothelium for reconstructive
surgery in the genitourinary tract.
PMID- 9643673
TI - Optimal parameters for transurethral intravesical electrostimulation determined
in an experiment in the rat.
AB - OBJECTIVE: Parameters of current for transurethral intravesical
electrostimulation (IVES) are studied in the rat to determine the settings which
elicit optimal detrusor contractions. Action mechanisms related to the induction
of detrusor contractions upon ives are also investigated. METHODS: In 24 female
Wistar rats transurethral IVES was performed using 95 combinations of different
pulse durations and frequencies. The reference electrode was positioned in the
bladder, in the urethra, or on the abdominal wall. RESULTS AND CONCLUSIONS: The
optimal detrusor contractions are induced in the rat with a current of 10 Hz
frequency and 20 ms pulse duration. A mathematical correlation is found between
frequency and pulse duration which permits to determine the best combination.
Evidence for the existence of local factors inducing detrusor contractions by
IVES is given. The detrusor contractions proved independent of the position of
the reference electrode.
PMID- 9643674
TI - Neobladder and bladder replacement.
PMID- 9643675
TI - Human pancreatic secretory trypsin inhibitor. Distribution, actions and possible
role in mucosal integrity and repair.
AB - Pancreatic secretory trypsin inhibitor is a potent protease inhibitor which was
originally identified in the pancreas. It has subsequently been shown to be
present in mucus-secreting cells throughout the gastrointestinal tract and also
in the kidney, lung and breast. Its major roles are likely to be to prevent
premature activation of pancreatic proteases and to decrease the rate of mucus
digestion by luminal proteases within the stomach and colon. In addition, PSTI
increases the proliferation of a variety of cell lines and stimulates cell
migration, possibly acting via the EGF receptor. These findings suggest that PSTI
may also be involved in both the early and late phases of the healing response
following injury. Further studies including the production of transgenic
overexpression and knockout models should help elucidate the physiological
function of this peptide.
PMID- 9643676
TI - Increased cytosolic Ca2+ amplifies oxygen radical-induced alterations of the
ultrastructure and the energy metabolism of isolated rat pancreatic acinar cells.
AB - BACKGROUND: Oxygen radicals have been implicated as important mediators in the
early pathogenesis of acute pancreatitis, but the mechanism by which they produce
pancreatic tissue injury remains unclear. We have, therefore, investigated the
effects of oxygen radicals on isolated rat pancreatic acinar cells as to the
ultrastructure, cytosolic Ca2+ concentration and energy metabolism. METHODS:
Acinar cells were exposed to an oxygen radical-generating system consisting of
xanthine oxidase, hypoxanthine and chelated iron ions. Cell injury was assessed
by LDH release and electron microscopy. Cytosolic Ca2+ levels and mitochondrial
membrane potential were determined by flow cytometry; adenine nucleotide
concentrations by HPLC. Mitochondrial dehydrogenase activity was measured by
spectrophotometric assay. RESULTS: Oxygen radicals damaged the plasma membrane as
shown by a 6-fold LDH increase in the incubation medium within 180 min. At the
ultrastructural level, mitochondria were the most susceptible to oxidative
stress. In correlation to the pronounced mitochondrial damage, the mitochondrial
dehydrogenase activity declined by 70%, whereas the mitochondrial membrane
potential was enhanced by 27% after 120 min. Together this may cause the 85%
decrease in the ATP concentration and the corresponding increase in ADP/AMP
observed in parallel. In addition, an immediate 26% increase in cytosolic Ca2+
was found, a change which could be inhibited by BAPTA, reducing cellular damage.
CONCLUSION: Cytosolic Ca2+ synergizes with oxygen radicals causing alterations of
the ultrastructure and energy metabolism of acinar cells which might contribute
to the cellular changes found in early stages of acute pancreatitis.
PMID- 9643677
TI - Pancreatitis-associated protein is upregulated in mouse pancreas during acute
pancreatitis.
AB - Pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein
strongly expressed during acute pancreatitis in the rat and human. We
hypothesized that its expression was part of a general and coordinated response
of the organ against aggression. An opposite pattern of PAP I mRNA expression has
recently been described in the mouse. The murine PAP I mRNA was described to be
highly expressed in normal pancreas and down-regulated during pancreatitis. The
important implications of these unexpected findings led us to investigate the
expression of murine PAP I in cerulein-induced pancreatitis. Northern blot
analysis demonstrated a very low level of PAP I mRNA in the healthy mouse
pancreas and strong overexpression during acute pancreatitis. Western blot
analysis confirmed that changes in pancreatic PAP I levels were parallel to those
of the mRNA and the protein was localized by immunohistochemistry to the acinar
cells. It was concluded that, during the course of acute pancreatitis, the
pattern of PAP I expression in the mouse pancreas was comparable to that already
observed in the rat and human. Although we have no explanation for the
discrepancy between our results and those recently reported, the expression
pattern of PAP I in the mouse exocrine pancreas described in the present study
suggests that the pancreatic response to aggression might be conserved in
mammals.
PMID- 9643678
TI - Immunohistochemical characterization of the pancreatic cellular infiltrate in
normal pancreas, chronic pancreatitis and pancreatic carcinoma.
AB - BACKGROUND/AIMS: Chronic pancreatitis is histologically characterized by an
extended fibrosis and infiltration of leukocytes. We intended to differentiate
the infiltration to evaluate the inflammatory process. METHODS: Samples of
tissues of normal pancreas (NP, n = 12), of chronic pancreatitis (CP, n = 7), and
pancreatic tissues surrounding pancreatic carcinoma (CA, n = 7) were investigated
by immunohistochemical staining using the APAAP technique. RESULTS: In normal
pancreas, mononuclear cells (47.1 +/- 26.0 cells/mm2) were observed with a
predominance of macrophages (56.3%) and T lymphocytes (31.3%) which were
differentiated in CD8+ lymphocytes (9.3 +/- 7.2 cells/ mm2) and CD4+ lymphocytes
(6.7 +/- 3.2 cells/mm2). Rarely, plasma cells (5.3%) and B lymphocytes (7.1%)
could be detected. In pancreatic tissue of patients with CP and in CA there was a
significant increase of mononuclear cells to 264.4 +/- 120.3 cells/mm2 and 284.3
+/- 67.8 cells/mm2, respectively. In both diseases percentages of T lymphocytes
(CP: 50.5%; CA: 48.1%) were higher than in normal controls. CD4+/CD8+ ratio of
0.77 in CP and 0.82 in CA demonstrated a predominance of CD8+ cells compared to
the peripheral blood. In NP and CA, nearly all T lymphocytes expressed CD45R0
identifying memory cells, while only 58% of T lymphocytes were CD45R0 positive in
CP. CONCLUSION: Our data suggest that the investigated cases of CP were of a
common inflammatory type rather than due to an autoimmunological reaction. CD8+ T
lymphocytes were the predominant T cell subset in the inflammatory infiltrates in
both CP and CA.
PMID- 9643679
TI - Defending data-monitoring committees.
PMID- 9643680
TI - Chest pain and normal coronary arteriograms: role of "microvascular spasm".
PMID- 9643681
TI - BSE: the final resting place.
PMID- 9643682
TI - Prognostic factors for success of endometrial ablation and resection.
PMID- 9643683
TI - Health care for seafarers.
PMID- 9643684
TI - Surgery for congenital dislocation of the hip in the UK as a measure of outcome
of screening. MRC Working Party on Congenital Dislocation of the Hip. Medical
Research Council.
AB - BACKGROUND: Universal clinical screening for congenital dislocation of the hip to
detect hip instability in neonates was introduced in the UK as a national policy
in 1969, but its effectiveness is not known. We aimed to assess the extent to
which surgery for congenital dislocation of the hip is the result of a failure of
detection through screening or follows non-surgical treatment after detection by
screening. METHODS: We established a national orthopaedic surveillance scheme and
used routine hospital data for inpatients for 20% of births in the UK (Scotland
and the Northern and Wessex regions) to ascertain the number of children aged
under 5 years per 1000 livebirths who had received at least one operative
procedure for congenital dislocation of the hip from April, 1993, to April, 1994.
Estimates of the incidence of operative procedures were adjusted for under
ascertainment by capture-recapture techniques. FINDINGS: The ascertainment
adjusted incidence of a first operative procedure for congenital dislocation of
the hip in the UK was 0.78 per 1000 livebirths (95% CI 0.72-0-84). Congenital
dislocation of the hip had not been detected by routine screening in 222 (70%) of
318 children reported to the national orthopaedic surveillance scheme. In 112
(35%) children the diagnosis was made primarily as a result of parental concern.
67 (21%) children had previously received non-surgical treatment. In Scotland and
the Northern and Wessex regions, 81 cases were notified to the national
orthopaedic surveillance scheme, 62 cases were identified only through routine
hospital data on inpatients, and an estimated 20 cases were not identified by
either source, making a total of 163 cases. Thus, 81 (50%) of these 163 cases
were identified by surveillance, 125 (77%) by routine data, and 143 (88%) by both
sources. INTERPRETATION: The incidence of a first operative procedure for
congenital dislocation of the hip in the UK was similar to that reported before
screening was introduced. In most children who received surgery, congenital
dislocation of the hip was not detected by screening. Formal evaluation of
current and alternative screening policies, including universal primary
ultrasound imaging, is needed.
PMID- 9643685
TI - Randomised comparison of primary stent placement versus primary angioplasty
followed by selective stent placement in patients with iliac-artery occlusive
disease. Dutch Iliac Stent Trial Study Group.
AB - BACKGROUND: Percutaneous transluminal angioplasty (PTA) is a safe, simple, and
successful treatment for intermittent claudication caused by iliac-artery
occlusive disease. Primary stent placement has been proposed as more effective
than PTA. We compared the technical results and clinical outcomes of two
treatment strategies-primary placement of a stent across the stenotic segment of
the iliac artery, or primary PTA followed by selective stent placement when
haemodynamic results were inadequate. METHODS: We randomly assigned 279 patients
with intermittent claudication, recruited from departments of vascular surgery,
either to direct stent placement (group I, n=143) or primary angioplasty (group
II, n=136), with subsequent stent placement in case of a residual mean pressure
gradient greater than 10 mm Hg across the treated site. The main inclusion
criterion was intermittent claudication on the basis of iliac-artery stenosis of
more than 50%, proven by angiography. All patients had a clinical assessment
before intervention and at 3, 12, and 24 months. Clinical success was defined as
improvement of at least one clinical category. Secondary endpoints were initial
technical results, procedural complications, cumulative patency as assessed by
duplex ultrasonography, and quality of life. FINDINGS: In group II, selective
stent placement was done in 59 (43%) of the 136 patients. The mean follow-up was
9.3 months (range 3-24). Initial haemodynamic success and complication rates were
119 (81%) of 149 limbs and 6 (4%) of 143 limbs (group I) versus 103 (82%) of 126
limbs and 10 (7%) of 136 limbs (group II), respectively. Clinical success rates
at 2 years were 29 (78%) of 37 patients and 26 (77%) of 34 patients in groups I
and II, respectively (p=0.6); however, 43% and 35% of the patients, respectively,
still had symptoms. Quality of life improved significantly after intervention
(p<0.05) but we found no difference between the groups during follow-up. 2-year
cumulative patency rates were similar at 71% versus 70% (p=0.2), respectively, as
were reintervention rates at 7% versus 4%, respectively (95% CI -2% to 9%).
INTERPRETATION: There were no substantial differences in technical results and
clinical outcomes of the two treatment strategies both at short-term and long
term follow-up. Since angioplasty followed by selective stent placement is less
expensive than direct placement of a stent, the former seems to be the treatment
of choice for lifestyle-limiting intermittent claudication caused by iliac artery
occlusive disease.
PMID- 9643686
TI - Role of human-milk lactadherin in protection against symptomatic rotavirus
infection.
AB - BACKGROUND: Human milk contains a 46 kDa mucin-associated glycoprotein,
lactadherin, which binds specifically to rotavirus and inhibits its replication.
This study tested the hypothesis that lactadherin protects against symptoms of
rotavirus infection. METHODS: 200 infants in Mexico City were recruited at birth
and monitored by regular stool EIA for rotavirus, serology, and recording of
feeding and stool patterns. Milk samples were obtained from the mothers weekly
until 4 weeks post partum then monthly. The sample taken immediately before an
infant's episode of rotavirus infection was assayed for lactadherin,
butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic
if diarrhoea occurred in the 5 days before or after detection of the virus.
FINDINGS: 31 infants developed rotavirus infection; 15 were symptomatic and 16
had no symptoms. The median concentration of lactadherin in the milk samples
(obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180)
microg/mL in the asymptomatic group and 29-2 (6.2-103-4) microg/mL in the
symptomatic group. Although these medians did not differ significantly, in
logistic regression analysis adjusted for age at infection and secretory IgA
concentration there was a significant difference between the groups (p=0O01). No
association between symptom status and concentrations of butyrophilin, mucin, or
secretory IgA was found. INTERPRETATION: Protection against rotavirus by human
milk is associated with the glycoprotein lactadherin. This association is
independent of products of the secretory immune system.
PMID- 9643687
TI - Angina pectoris caused by coronary microvascular spasm.
AB - BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced
vasodilator capacity of the coronary microvessels is implicated as a cause of
angina during exercise, but the mechanism of angina at rest is not known. Our aim
was to test the hypothesis that primary hyperconstriction (spasm) of coronary
microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces
coronary artery spasm in patients with variant angina. We tested the effects of
intracoronary acetylcholine at graded doses in 117 consecutive patients with
chest pain (at rest, during exertion, or both) and no flow-limiting (>50%)
organic stenosis in the large epicardial coronary arteries. We also assessed the
metabolism of myocardial lactate during acetylcholine administration in 36 of the
patients by measurement of lactate in paired blood samples from the coronary
artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large
artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest
pain. The 29 patients with microvascular spasm developed angina-like chest pain,
ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients)
or after administration of acetylcholine (27 patients) without spasm of the large
epicardial coronary arteries. Testing of paired samples of arterial and coronary
sinus venous blood showed that lactate was produced during angina attack in nine
of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer
coronary risk factors (p<0.01) in patients with microvascular spasm than in those
with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and
resultant myocardial ischaemia may be the cause of chest pain in a subgroup of
patients with microvascular angina.
PMID- 9643689
TI - A man who lost weight and his sight.
PMID- 9643688
TI - Expression of genes that contribute to proliferative and metastatic ability in
breast cancer resected during various menstrual phases.
AB - BACKGROUND: Retrospective studies show significant improvements in survival among
women who had breast cancer resected during the luteal phase of their menstrual
cycle compared with the follicular phase. We hypothesised that tumour tissue
would show cyclical changes in expression of genes whose products might
contribute to metastatic potential. METHODS: We studied 32 premenopausal women
with operable breast cancer. We assayed hormones to define more accurately the
menstrual phase during which surgery was done. We used northern blot analysis of
RNA from fresh-frozen tumour specimens to study the patterns of expression of
genes for proteolytic enzymes (cysteine proteinase cathepsin L and aspartyl
proteinase cathepsin D; matrix metalloproteinases MMP-9 and MMP-2), tissue
inhibitors of metalloproteinases TIMP-1 and TIMP-2, and TP53. RESULTS: There was
a significantly higher level of expression of RNA for cathepsin L, MMP-9, and
TP53 (p=0.005, 0.03, 0.03, respectively) in tumours that were resected during the
follicular and periovulatory phases of the menstrual cycle than at other times in
the cycle. A similar but non-significant trend was seen for MMP-2 and cathepsin
D. A non-significant trend in the opposite direction was seen for TIMP-1 and TIMP
2. INTERPRETATION: We found that tumour expression of genes that may contribute
to proliferative capacity and metastatic potential can change in breast cancer
during the course of the menstrual cycle. The finding could provide a molecular
explanation for the reports of improved survival in some breast-cancer patients
whose tumours were removed during the luteal phase of the menstrual cycle. Larger
studies are required to extend our study, assess mechanisms of gene regulation,
and verify any relevant influence in long-term survival.
PMID- 9643690
TI - Explosive spread of HIV-1 and sexually transmitted diseases in Cambodia.
PMID- 9643691
TI - Immunosuppressive drugs and HHV-8 in a patient with a renal transplant and
Kaposi's sarcoma.
PMID- 9643692
TI - Treatment of cutaneous leishmaniasis with nitric-oxide donor.
PMID- 9643693
TI - Do doctors have an increased rate of Caesarean section?
PMID- 9643694
TI - Ooplasmic injections of secondary spermatocytes for non-obstructive azoospermia.
PMID- 9643695
TI - Pancreatitis after losartan.
PMID- 9643696
TI - Reporting of attributable and relative risks, 1966-97.
PMID- 9643697
TI - Avoidable deaths from vehicle accidents in Modena, Italy.
PMID- 9643698
TI - 3-year follow-up of patients randomised in the metoprolol in dilated
cardiomyopathy trial. The Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study
Group.
PMID- 9643699
TI - Cryptococcosis and starling nests.
PMID- 9643700
TI - Inhaled nitric oxide and inhibition of platelet aggregation in critically ill
neonates.
PMID- 9643701
TI - Endurance training during a twin pregnancy in a marathon runner.
PMID- 9643702
TI - Adverse drug reactions remain a major cause of death.
PMID- 9643703
TI - Genetic basis for idiopathic scoliosis brought a step nearer.
PMID- 9643704
TI - Retinoids promising in Kaposi's sarcoma trials.
PMID- 9643705
TI - Telomeres: keys to senescence and cancer.
PMID- 9643706
TI - A happy season for biomedical research.
PMID- 9643707
TI - Austria investigates illegal blood trade.
PMID- 9643708
TI - Failed coronary thrombolysis.
PMID- 9643709
TI - Thalidomide: was the tragedy preventable?
PMID- 9643710
TI - 150 years of pharmacovigilance.
PMID- 9643711
TI - A sort of progress.
PMID- 9643712
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643713
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643714
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643715
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643716
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643717
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643718
TI - Interpretation of Thrombosis Prevention Trial.
PMID- 9643719
TI - Early amniocentesis for biochemical genetic prenatal diagnosis.
PMID- 9643720
TI - Disease burden in sub-Saharan Africa.
PMID- 9643721
TI - Disease burden in sub-Saharan Africa.
PMID- 9643722
TI - Hepatitis C.
PMID- 9643723
TI - Hepatitis C.
PMID- 9643724
TI - Hepatitis C.
PMID- 9643725
TI - Antiepileptic drugs in developing countries.
PMID- 9643726
TI - Lack of specificity of procalcitonin for sepsis diagnosis in premature infants.
PMID- 9643727
TI - First clinical isolate of vancomycin-intermediate Staphylococcus aureus in a
French hospital.
PMID- 9643728
TI - Height measurements and stretching.
PMID- 9643729
TI - Fish consumption and major depression.
PMID- 9643730
TI - Food rations for refugees.
PMID- 9643731
TI - HIV-1 infection and prostitutes.
PMID- 9643732
TI - Need for holistic view of illness.
PMID- 9643733
TI - Futility and surgeons.
PMID- 9643734
TI - Misled by moonshine.
PMID- 9643735
TI - Medical advocacy for the oppressed.
PMID- 9643736
TI - ISAAC--a hypothesis generator for asthma? International Study of Asthma and
Allergies in Childhood.
PMID- 9643737
TI - Catechol-O-methyltransferase inhibitors for treatment of Parkinson's disease.
PMID- 9643738
TI - What risk of infection with IUD use.
PMID- 9643739
TI - Torticollis--what is straight ahead?
PMID- 9643740
TI - Training in orthopaedic spinal surgery.
PMID- 9643741
TI - Worldwide variation in prevalence of symptoms of asthma, allergic
rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma
and Allergies in Childhood (ISAAC) Steering Committee.
AB - BACKGROUND: Systematic international comparisons of the prevalences of asthma and
other allergic disorders in children are needed for better understanding of their
global epidemiology, to generate new hypotheses, and to assess existing
hypotheses of possible causes. We investigated worldwide prevalence of asthma,
allergic rhinoconjunctivitis, and atopic eczema. METHODS: We studied 463,801
children aged 13-14 years in 155 collaborating centres in 56 countries. Children
self-reported, through one-page questionnaires, symptoms of these three atopic
disorders. In 99 centres in 42 countries, a video asthma questionnaire was also
used for 304,796 children. FINDINGS: We found differences of between 20-fold and
60-fold between centres in the prevalence of symptoms of asthma, allergic
rhinoconjunctivitis, and atopic eczema, with four-fold to 12-fold variations
between the 10th and 90th percentiles for the different disorders. For asthma
symptoms, the highest 12-month prevalences were from centres in the UK,
Australia, New Zealand, and Republic of Ireland, followed by most centres in
North, Central, and South America; the lowest prevalences were from centres in
several Eastern European countries, Indonesia, Greece, China, Taiwan, Uzbekistan,
India, and Ethiopia. For allergic rhinoconjunctivitis, the centres with the
highest prevalences were scattered across the world. The centres with the lowest
prevalences were similar to those for asthma symptoms. For atopic eczema, the
highest prevalences came from scattered centres, including some from Scandinavia
and Africa that were not among centres with the highest asthma prevalences; the
lowest prevalence rates of atopic eczema were similar in centres, as for asthma
symptoms. INTERPRETATION: The variation in the prevalences of asthma, allergic
rhinoconjunctivitis, and atopic-eczema symptoms is striking between different
centres throughout the world. These findings will form the basis of further
studies to investigate factors that potentially lead to these international
patterns.
PMID- 9643742
TI - Randomised, double-blind, placebo-controlled trial of human recombinant growth
hormone in patients with chronic heart failure due to dilated cardiomyopathy.
AB - BACKGROUND: Some studies have suggested that treatment with recombinant human
growth hormone (rhGH) increases left-ventricular mass and improves haemodynamic
and functional status in patients with heart failure due to dilated
cardiomyopathy. We did a double-blind, randomised, placebo-controlled study of
rhGH in patients with chronic heart failure due to dilated cardiomyopathy.
METHODS: 50 patients (43 men) were randomly allocated treatment with subcutaneous
rhGH (2 IU daily) or placebo for a minimum of 12 weeks. The primary endpoints
were the effects on left-ventricular mass and systolic wall stress. The secondary
endpoints were the effects on left-ventricular size and function. Data were
analysed by intention to treat. FINDINGS: Patients in the rhGH group had an
increase in left-ventricular mass compared with those in the placebo group (27%,
p=0.0001). There was no significant difference in left-ventricular systolic wall
stress, mean blood pressure, or systemic vascular resistance between the two
groups. New York Heart Association functional class, left-ventricular ejection
fraction, and distance on the 6 min walking test were unchanged. The change in
serum insulin-like growth factor (IGF)-I concentrations (rhGH 77 ng/mL; placebo
19 ng/mL, GH vs placebo p=0.0001) was significantly related to the change in left
ventricular mass (r=0.55, p=0.0001). One patient in the rhGH group was withdrawn
at 6 weeks because of worsening heart failure. INTERPRETATION: There is a
significant increase in left-ventricular mass in patients with dilated
cardiomyopathy given rhGH but this is not accompanied by an improvement in
clinical status. Changes in left-ventricular mass are related to changes in serum
IGF-I concentrations. Whether a longer treatment period would provide clinical
benefits and decrease mortality is unknown.
PMID- 9643743
TI - Complications of use of intrauterine devices among HIV-1-infected women.
AB - BACKGROUND: A WHO expert group and the International Planned Parenthood
Federation recommend against use of intrauterine devices (IUDs) in HIV-1-infected
women based on theoretical concerns about pelvic infection and increased blood
loss. We investigated whether the risk of complications after IUD insertion is
higher in HIV-1-infected women than in non-infected women. METHODS: 649 (156 HIV
1 infected 493 non-infected) women in Nairobi, Kenya, who requested and met local
eligibility criteria for insertion of an IUD were enrolled. We gathered
information on IUD-related complications, including pelvic inflammatory disease,
removals due to infection, pain, or bleeding, expulsions, and pregnancies at 1
and 4 months after insertion. Patients' HIV-1 status was masked from physicians.
FINDINGS: Complications were identified in 48 of 615 women (11 [7.6%] HIV-1
infected women, 37 [7.9%] non-infected). Incident pelvic inflammatory disease
(two [1.4%] HIV-1 infected, one [0.2%] non-infected) and infection-related
complications (any tenderness, removal of IUD for infection or pain; ten [6.9%]
HIV-1 infected, 27 [5.7%] non-infected) were also rare and similar in the two
groups. Complication rates were similar by CD4 (immune) status. Multivariate
analyses suggested no association between HIV-1 infection and increased risks for
overall complications (odds ratio 0.8 [95% CI 0.4-1.7]) or infection-related
complications (1.0 [0.5-2.3]), adjusted for marital status, study site, previous
IUD use, ethnic origin, and frequency of sexual intercourse, but a slight
increase cannot be ruled out. INTERPRETATION: Our data suggest that IUDs may be a
safe contraceptive method for appropriately selected HIV-1-infected women with
continuing access to medical services.
PMID- 9643744
TI - Mass screening for lung cancer with mobile spiral computed tomography scanner.
AB - BACKGROUND: The incidence of and mortality from lung cancer have increased
steadily. Most lung cancers are not localised when first detected, but early
detection is mandatory to improve prognosis. Since curable early cases are hard
to visualise with conventional chest radiography, a new diagnostic means must be
found. We assessed whether population-based mass screening with a spiral computed
tomography scanner could contribute substantially to detection of smaller
cancers, and decrease mortality. METHODS: In 1996, we screened in a mobile unit
5483 individuals from the general population of Matsumoto, Japan, aged between 40
years and 74 years who had undergone annual chest radiography (miniature
fluorophotography) and cytological assessment of sputum. All participants had a
low-dose X-ray spiral computed tomography (CT) scan of the thorax; 3967 also
underwent miniature fluorophotography. We compared smokers and non-smokers.
Further assessments were done for probably benign but suspicious lesions;
suspicion of cancer; and indeterminate small nodules by chest radiography and
conventional CT, with additional transbronchial biopsy when possible. Thoracotomy
was recommended when it was strongly suspected that the patients had lung cancer.
FINDINGS: 19 patients were diagnosed as having lung cancer--14 with suspicion of
lung cancer, three with benign but suspicious lesions, and two with indeterminate
small nodules. 18 cases were surgically confirmed, and one was clinically
diagnosed. The mean size of lesions was 17 mm (range 6-47). In four of 19
patients, lung abnormality was seen on CT and miniature fluorophotography. The
lung-cancer detection rate with CT was 0.48%, significantly higher than the 0.03
0.05% for standard mass assessments done previously in the same area. CT missed
one case that was found solely on a sputum cytology examination. INTERPRETATION:
Our results show that miniature fluorophotography or conventional chest
radiography, which have been the main diagnostic techniques for lung cancer,
showed few small cancers. CT was more accurate in mass screening for lung cancer
and led to early detection and an accurate diagnosis of lung cancer, and should
be considered in future health plans.
PMID- 9643745
TI - Malaria in Maremma, Italy.
AB - BACKGROUND: In August, 1997, a woman with no history of travel to malarious
regions developed Plasmodium vivax malaria. She lived in a rural area of Italy
where indigenous Anophyles labranchiae mosquitoes were present. METHODS AND
FINDINGS: An environmental investigation was done within a 3 km radius of the
patient's house. Adult mosquitoes and larvae were collected and examined by PCR
with the gene for plasmodium circumsporozoite protein as target. About 200 people
living in the area were interviewed to detect possible carriers of P. vivax.
FINDINGS: None of the mosquitoes captured were carrying any malarial organisms.
The house-to-house investigation identified a 7-year-old girl who had had a
feverish illness a few days after her arrival in Italy from India, and who, 3
months later, still had P. vivax in her blood; she and her mother had
antimalarial antibodies. INTERPRETATION: These investigations suggest that the
index case of malaria was caused by local anopheline mosquitoes infected with
exogenous P. vivax.
PMID- 9643746
TI - Teapot myositis.
PMID- 9643747
TI - Single-surgeon thoracoscopic surgery with a voice-controlled robot.
PMID- 9643748
TI - Terlipressin-exacerbated hypokalaemia.
PMID- 9643749
TI - Two subtypes of HIV-1 among injection-drug users in southern China.
PMID- 9643750
TI - Genotype at codon 129 and susceptibility to Creutzfeldt-Jakob disease.
PMID- 9643751
TI - Pregnancy in women with observed focal nodular hyperplasia of the liver.
PMID- 9643752
TI - Renal dysfunction accompanying oral creatine supplements.
PMID- 9643754
TI - Pro-convulsant effects of oral melatonin in neurologically disabled children.
PMID- 9643753
TI - PlA2 polymorphism and efficacy of aspirin.
PMID- 9643755
TI - Chlamydia pneumoniae in vascular tissues from heart-transplant donors.
PMID- 9643756
TI - Systemic absorption of progesterone from Progest cream in postmenopausal women.
PMID- 9643757
TI - Lamivudine-induced paronychia.
PMID- 9643758
TI - Issue of lower limit for LDL cholesterol unresolved.
PMID- 9643759
TI - Peter Barnes: a breath of fresh air in asthma research.
PMID- 9643760
TI - North Korea: where children look like old men.
PMID- 9643761
TI - Antidepressant dependence controversy moves to Internet.
PMID- 9643763
TI - Country profile: India.
PMID- 9643764
TI - Altering molecular mechanisms to prevent sudden arrhythmic death.
AB - Trials of drug treatment for prevention of sudden arrhythmic death have been
disappointing, perhaps because suppressive therapy with arrhythmic agents fails
to address the mechanisms leading to electrophysiological failure. We propose
that preventive treatment should pay more attention to molecular mechanisms
responsible for the progression of cardiac disease to electrophysiological
failure. Most sudden cardiac deaths occur in people with atherogenic
dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of
dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory
prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis
include phospholipids and leucotrienes acting through the platelet-activating
factor and peroxisome proliferator-activated-receptor pathways. There are drugs
available to test the hypothesis of dyslipidaemias-specific prevention of
electrophysiological failure.
PMID- 9643765
TI - Setting targets to address inequalities in health.
PMID- 9643766
TI - Effectiveness of pneumococcal vaccine.
PMID- 9643767
TI - Effectiveness of pneumococcal vaccine.
PMID- 9643768
TI - Effectiveness of pneumococcal vaccine.
PMID- 9643769
TI - Effectiveness of pneumococcal vaccine.
PMID- 9643770
TI - Lung transplantation.
PMID- 9643771
TI - Do Asian HBV carriers differ from non-Asian carriers?
PMID- 9643772
TI - Azithromycin, the multidrug-resistant protein, and cystic fibrosis.
PMID- 9643773
TI - Iron overload and mitochondrial diseases.
PMID- 9643774
TI - Minimal residual disease in children with acute lymphoblastic leukaemia.
PMID- 9643775
TI - Telomere shortening in recipients of bone-marrow transplants.
PMID- 9643776
TI - Intravenous immunoglobulins and transforming growth factor beta.
PMID- 9643777
TI - Homocysteine and endothelial vascular function.
PMID- 9643778
TI - Quinolone-resistant Salmonella typhi in Vietnam.
PMID- 9643779
TI - New-variant Creutzfeldt-Jakob disease and treatment of haemophilia. Executive
Committee UK Haemophilia Directors' Organisation.
PMID- 9643780
TI - Ligase chain reaction assay for Chlamydia trachomatis during the menstrual cycle.
PMID- 9643781
TI - Laser pointers: the facts, media hype, and hysteria.
PMID- 9643782
TI - Medicine and modern physics.
PMID- 9643783
TI - Chronic fatigue syndrome.
PMID- 9643785
TI - "Let no man name death to me".
PMID- 9643784
TI - Hard sell on health.
PMID- 9643786
TI - Defensible secrecy, a very rare bird.
PMID- 9643787
TI - Action against antibiotic resistance: no time to lose.
PMID- 9643788
TI - Teaching heart-failure patients how to breathe.
PMID- 9643789
TI - Biomarkers of asthma.
PMID- 9643790
TI - Not all fat is alike.
PMID- 9643791
TI - Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and
risk of hip fractures in elderly people.
AB - BACKGROUND: Tricyclic antidepressants (TCAs) are associated with an increased
risk of falls and hip fractures in elderly people. Selective serotonin-reuptake
inhibitors (SSRIs) are reported to be better tolerated than TCAs. We investigated
the risk of hip fractures associated with SSRIs and TCAs. METHODS: This case
control study used administrative healthcare data from the province of Ontario,
Canada. 8239 cases-patients aged 66 years or older, treated in hospital between
April, 1994, and March, 1995, for hip fracture-were each matched for age and sex
to five controls. Logistic regression was used to calculate the odds ratio for
hip fracture with adjustment for potential confounding effects produced by
concomitant drug use and comorbidity. FINDINGS: With participants who had no
exposure to antidepressants as the reference category, the adjusted odds ratio
for hip fracture was 2.4 (95% CI 2.0-2.7) for exposure to SSRIs, 2.2 (1.8-2.8)
for exposure to secondary-amine TCAs, and 1.5 (1.3-1.7) for exposure to tertiary
amine TCAs. For all types of antidepressants, current use was associated with a
higher risk of hip fracture than former use. The odds ratios for hip fracture
were higher for new current users than for continuous current users in all three
drug classes. The proportion of current use in the low-dose range was 22% for
SSRIs, 50% for secondary-amine TCAs, and 58% for tertiary-amine TCAs.
INTERPRETATION: Exposure to any of the three classes of antidepressants is
associated with a significant increase in the risk of hip fracture. Despite
differences in dose distribution, this analysis suggests that SSRIs do not offer
an advantage over TCAs in terms of risk of hip fracture.
PMID- 9643792
TI - Effect of breathing rate on oxygen saturation and exercise performance in chronic
heart failure.
AB - BACKGROUND: In chronic heart failure (CHF), impaired pulmonary function can
independently contribute to oxygen desaturation and reduced physical activity. We
investigated the effect of breathing rate on oxygen saturation and other
respiratory indices. METHODS: Arterial oxygen saturation (SaO2) and respiratory
indices were recorded during spontaneous breathing (baseline) and during
controlled breathing at 15, six, and three breaths per min in 50 patients with
CHF and in 11 healthy volunteers (controls). 15 patients with CHF were randomly
allocated 1 month of respiratory training to decrease their respiratory rate to
six breaths per min. Respiratory indices were recorded before training, at the
end of training, and 1 month after training. FINDINGS: During spontaneous
breathing, mean SaO2 was lower in CHF patients than in controls (91-4% [SD 0.4]
vs 95.4% [0.2], p<0.001). Controlled breathing increased SaO2 at all breathing
rates in patients with CHF. Compared with baseline, minute ventilation increased
at 15 breaths per min (+45.9% [9.8], p<0.01), did not change at six breaths per
min, and decreased at three breaths per min (-40.3% [4.8], p<0.001). In the nine
CHF patients who had 1 month of respiratory training, resting SaO2 increased from
92.5% (0.3) at baseline to 93.2% (0.4) (p<0.05), their breathing rate per min
decreased from 13.4 (1.5) to 7.6 (1.9) (p<0.001), peak oxygen consumption
increased from 1157 (83) to 1368 (110) L/min (p<0.05), exercise time increased
from 583 (29) to 615 (23) min/s (p<0.05), and perception of dyspnoea reduced from
a score of 19.0 (0.4) to 17.3 (0.9) on the Borg scale (p<0.05). There were no
changes in the respiratory indices in the patients who did not have respiratory
training. INTERPRETATION: Slowing respiratory rate reduces dyspnoea and improves
both resting pulmonary gas exchange and exercise performance in patients with
CHF.
PMID- 9643793
TI - Is current eye-care-policy focus almost exclusively on cataract adequate to deal
with blindness in India?
AB - BACKGROUND: India's National Programme for Control of Blindness focuses almost
exclusively on cataract, based on a national survey done in the 1980s which
reported that cataract caused 80% of the blindness in India. No current
population-based data on the causes of blindness in India are available. We
assessed the rate and causes of blindness in an urban population in southern
India. METHODS: We selected 2954 participants by stratified, random, cluster,
systematic sampling from Hyderabad city. Eligible participants were interviewed
and given a detailed ocular assessment, including visual acuity, refraction,
slitlamp biomicroscopy, applanation intraocular pressure, gonioscopy, dilatation,
grading of cataract, stereoscopic fundus assessment, and automated-threshold
visual fields. FINDINGS: 2522 participants, including 1399 aged 30 years or more,
were assessed. 49 participants (all aged > or =30 years) were blind (presenting
distance visual acuity <6/60 or central visual field <200 in the better eye). The
rate of blindness among those aged 30 years or more, adjusted for age and sex,
was 3.08% ([95% CI 1.95-4.21]). Causes included cataract (29.7%), retinal disease
(17.1%), corneal disease (15.4%), refractive error (12.5%), glaucoma (12.1%), and
optic atrophy (11.0%). 15.7% of the blindness caused by visual-field constriction
would have been missed without visual-field examination. Also without visual
field and detailed dilated-fundus assessments, blindness attributed to cataract
would have been overestimated by up to 75.8%. If the use of cataract surgery in
this urban population was half that found in this study, which simulates the
situation in rural India, cataract would have caused 51.8% (39.4-64.2) of
blindness, significantly less than the 80% accepted by current policy.
INTERPRETATION: Much of the blindness in this Indian population was due to non
cataract causes. The previous national survey did not include detailed dilated
fundus assessment and visual-field examination which could have led to
overestimation of cataract as a cause of blindness in India. Policy-makers in
India should encourage well-designed population-based epidemiological studies
from which to develop a comprehensive long-term policy on blindness in addition
to dealing with cataract.
PMID- 9643794
TI - Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure.
AB - BACKGROUND: Nitric oxide (NO) gas concentrations are high in the expired air of
individuals with asthma, but not consistently so in the expired air of people
with pneumonia. S-nitrosothiols are naturally occurring bronchodilators, the
concentrations of which are raised in the airways of patients with pneumonia.
Airway S-nitrosothiols have not been studied in asthma. METHODS: Tracheal S
nitrosothiol concentrations from eight asthmatic children in respiratory failure
were compared with those of 21 children undergoing elective surgery. RESULTS:
Mean S-nitrosothiol concentrations in asthmatic children were lower than in
normal children (65 [SD 45] nmol/L vs 502 [SD 429] nmol/L) and did not vary with
inspired oxygen concentration or airway thiol concentration. INTERPRETATION:
Severe asthma is associated with low concentrations of airway S-nitrosothiols.
This is the first reported deficiency of an endogenous bronchodilator in the
human asthmatic airway lining fluid. We suggest that S-nitrosothiol metabolism
may be a target for the development of new asthma therapies.
PMID- 9643795
TI - Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected
patients.
AB - BACKGROUND: DNA vaccination is known to generate immune responses against HIV-1
in animal models. We aimed to assess the efficacy of DNA vaccination in induction
of immune responses in HIV-1-infected human beings. METHODS: Nine symptom-free
HIV-1-infected patients were immunised with DNA constructs encoding the nef, rev,
or tat regulatory genes of HIV-1. The patients were selected for having no or low
antibody reactivities to these antigens. HIV-1-specific cytotoxic T-lymphocytes
(CTLs), precursor frequencies, and antigen-specific proliferative responses were
measured before, during, and after three immunisations over 6 months. FINDINGS:
Cellular immune reactivities against the HIV-1 regulatory proteins were absent or
low before DNA immunisation. DNA vaccination induced detectable memory cells in
all patients and specific cytotoxicity in eight patients. CTLs were MHC-class-I
restricted and mainly of CD8+ origin. In three patients the cellular activity was
transient, decreasing after an initial response. INTERPRETATION: DNA immunisation
with HIV-1 genes can induce specific cellular responses in human beings with no
apparent side-effects. It is theoretically possible that HIV-1-specific cytotoxic
responses to regulatory proteins could lead to infected cells being eliminated
before they have released new viral particles. However, it is possible that the
patients we selected responded less than would non-selected or non-infected
individuals. The small number of patients presented here does not allow
generalisation of our findings.
PMID- 9643796
TI - A woman who trembled, then had chorea.
PMID- 9643797
TI - No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel
disease or autism in a 14-year prospective study.
PMID- 9643798
TI - Severe premature coronary artery disease with protease inhibitors.
PMID- 9643799
TI - Hormone-receptor status of breast cancer in Papua New Guinea.
PMID- 9643800
TI - Presence of donor-specific DNA in plasma of kidney and liver-transplant
recipients.
PMID- 9643801
TI - A urinary marker for multiple sclerosis.
PMID- 9643803
TI - Improvement in renal cholesterol emboli syndrome after simvastatin.
PMID- 9643802
TI - HSV-1 in brain and risk of Alzheimer's disease.
PMID- 9643804
TI - Health anxiety in medical students.
PMID- 9643805
TI - UK drug misusers targeted for better clinical care.
PMID- 9643806
TI - USA continues federal ban on needle-exchange funding.
PMID- 9643807
TI - Thwarting the dwindling progression of cachexia.
PMID- 9643808
TI - Labour's disappointing first year for health.
PMID- 9643810
TI - From mustard gas to biowarfare--Congress tackles military medicine.
PMID- 9643811
TI - Onchocerciasis.
PMID- 9643812
TI - Critical ethical issues in clinical trials with xenotransplants.
PMID- 9643813
TI - Early gastric cancer: disease or pseudo-disease?
PMID- 9643814
TI - The poetry of genetics: or reading a genetic sequence--a literary model for
cellular mechanisms.
PMID- 9643815
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643816
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643817
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643818
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643819
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643820
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643821
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643822
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643823
TI - Autism, inflammatory bowel disease, and MMR vaccine.
PMID- 9643824
TI - Questions on breast-implants study.
PMID- 9643825
TI - Survival of patients with breast cancer and BRCA1 mutations.
PMID- 9643826
TI - Prenatal exposure to famine and health in later life.
PMID- 9643827
TI - Prenatal exposure to famine and health in later life.
PMID- 9643828
TI - Prenatal exposure to famine and health in later life.
PMID- 9643829
TI - Magnetic-resonance imaging in breast cancer.
PMID- 9643830
TI - Aboriginal health.
PMID- 9643832
TI - Sexual ill-health among blacks in the UK.
PMID- 9643831
TI - Aboriginal health.
PMID- 9643833
TI - World health.
PMID- 9643834
TI - World health.
PMID- 9643835
TI - Clinical experience of UK medical students.
PMID- 9643836
TI - Number-needed-to-treat to prevent one death.
PMID- 9643837
TI - China's trade in human organs.
PMID- 9643838
TI - Hereditary breast cancer, circa 1750.
PMID- 9643839
TI - Pyoderma gangrenosum.
PMID- 9643841
TI - Global public health: targeting inequities.
PMID- 9643842
TI - Private venture galvanizes public effort on Human Genome Project.
PMID- 9643843
TI - Cancer experts offer healthy dose of skepticism toward hype over antiangiogenesis
agents.
PMID- 9643844
TI - Guarded endorsement for Lyme disease vaccine.
PMID- 9643845
TI - From the Centers for Disease Control and Prevention. Prevalence and impact of
chronic joint symptoms--seven states, 1996.
PMID- 9643846
TI - From the Centers for Disease Control and Prevention. Strategies for providing
follow-up and treatment services in the National Breast and Cervical Cancer Early
Detection Program--United States, 1997.
PMID- 9643847
TI - Patients' views of direct access to specialists: an Israeli experience.
AB - CONTEXT: Surveys carried out among users of medical services can be a useful tool
for health care organizations in designing proper services. Specifically,
patients' views of direct access to specialists can be useful to health
organizations considering the gatekeeper model. OBJECTIVE: To assess patients'
opinions about direct access to specialists and referral to specialists through
their primary care physician. DESIGN: An intercept survey, in which patients were
interviewed at the randomly selected service provision sites, was carried out in
3 districts in Israel during 1995. A total of 1445 and 1289 patients were
interviewed in primary care and specialty clinics, respectively. SETTING: Primary
care and specialty clinics in 3 regions in Israel serving 750000 members of Kupat
Holim Clalit, Israel's largest sick fund. PARTICIPANTS: Hebrew-speaking members
of Kupat Holim Clalit who visited the primary care or specialty clinics in the 3
regions during the study period. MAIN OUTCOME MEASURES: Rate of preferences for
direct access to specialists and preferences for referral through primary care
physician. RESULTS: Fifty-two percent of the respondents preferred direct access
to specialists, while 48% preferred a referral from their primary care physician.
Multivariate logistic regression analysis indicated that the preference for
direct access was significantly lower among patients older than 45 years (odds
ratio [OR], 0.75; 95% confidence interval [CI], 0.62-0.91); patients whose
primary care physician was a specialist in family medicine (OR, 0.80; 95% CI,
0.67-0.97); and patients who were satisfied with their primary care physician
(OR, 0.34; 95% CI, 0.27-0.44). Preference for direct access was significantly
higher among more highly educated patients (OR, 1.38; 95% CI, 1.16-1.65) and
patients residing in Jerusalem (OR, 2.46; 95% CI, 2.05-2.95) and those younger
than 45 years who were dissatisfied with their family physician or a primary care
physician who was not board certified. If direct access was not available, 33% of
respondents would leave the sick fund and 48% would remain; 19% did not know.
CONCLUSIONS: Informing sick fund members, particularly the younger and more
educated among them, about the advantages of consulting with the primary care
physician, as well as providing specialty training in family medicine to primary
care physicians, may reduce patients' preference for direct access to
specialists.
PMID- 9643848
TI - Zafirlukast and Churg-Strauss syndrome.
PMID- 9643849
TI - Zafirlukast and Churg-Strauss syndrome.
PMID- 9643850
TI - Zafirlukast and Churg-Strauss syndrome.
PMID- 9643851
TI - Quality of care for elderly patients with pneumonia.
PMID- 9643852
TI - Quality of care for elderly patients with pneumonia.
PMID- 9643853
TI - Quality of care for elderly patients with pneumonia.
PMID- 9643854
TI - Time lag bias in publishing clinical trials.
PMID- 9643855
TI - Time lag bias in publishing clinical trials.
PMID- 9643856
TI - CCR5 genotype and mother-to-child HIV transmission.
PMID- 9643857
TI - Maternal smoking and inhibition of fetal growth factor.
PMID- 9643858
TI - Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle
size as risk factors for ischemic heart disease.
AB - CONTEXT: Epidemiological studies have established a relationship between
cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and
the risk of ischemic heart disease (IHD), but up to half of patients with IHD may
have cholesterol levels in the normal range. OBJECTIVE: To assess the ability to
predict the risk of IHD using a cluster of nontraditional metabolic risk factors
that includes elevated fasting insulin and apolipoprotein B levels as well as
small, dense LDL particles. DESIGN: Nested case-control study. SETTING: Cases and
controls were identified from the population-based cohort of the Quebec
Cardiovascular Study, a prospective study conducted in men free of IHD in 1985
and followed up for 5 years. PARTICIPANTS: Incident IHD cases were matched with
controls selected from among the sample of men who remained IHD free during
follow-up. Matching variables were age, smoking habits, body mass index, and
alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD
cases and controls. MAIN OUTCOME MEASURES: Ability of fasting insulin level,
apolipoprotein B level, and LDL particle diameter to predict IHD events, defined
as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary
death. RESULTS: The risk of IHD was significantly increased in men who had
elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL
particles, compared with men who had normal levels for 2 of these 3 risk factors
(odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate
adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol
(HDL-C) did not attenuate the relationship between the cluster of nontraditional
risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of
IHD in men having a combination of elevated LDL-C and triglyceride levels and
reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after
multivariate adjustment for fasting plasma insulin level, apolipoprotein B level,
and LDL particle size. CONCLUSION: Results from this prospective study suggest
that the measurement of fasting plasma insulin level, apolipoprotein B level, and
LDL particle size may provide further information on the risk of IHD compared
with the information provided by conventional lipid variables.
PMID- 9643859
TI - Zinc gluconate lozenges for treating the common cold in children: a randomized
controlled trial.
AB - CONTEXT: The common cold is one of the most frequently occurring illnesses and is
responsible for substantial morbidity and economic loss. Biochemical evidence
suggests that zinc may be an effective treatment, and zinc gluconate glycine
(ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults.
OBJECTIVE: To determine the efficacy of ZGG treatment of colds in children and
adolescents. DESIGN: A randomized, double-masked, placebo-controlled study.
SETTING: Two suburban school districts in Cleveland, Ohio. PATIENTS: A total of
249 students in grades 1 through 12 were enrolled within the first 24 hours of
experiencing at least 2 of 9 symptoms of the common cold. INTERVENTION: Zinc
lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day
(in grades 7-12). MAIN OUTCOME MEASURES: Time to resolution of cold symptoms
based on subjective daily symptom scores for cough, headache, hoarseness, muscle
ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and
sneezing. RESULTS: Time to resolution of all cold symptoms did not differ
significantly between students receiving zinc (n = 124) and those receiving
placebo (n = 125) (median, 9 days; 95% confidence interval [CI], 8-9 days;
median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no
significant differences in the time to resolution of any of the 9 symptoms
studied. Compared with controls, more students in the zinc group reported adverse
effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea
(29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%;
P=.03); and diarrhea (10.6% vs 4.0%; P=.05). CONCLUSIONS: In this community
based, randomized controlled trial, ZGG lozenges were not effective in treating
cold symptoms in children and adolescents. Further studies with virologic testing
are needed to clarify what role, if any, zinc may play in treating cold symptoms.
PMID- 9643860
TI - Impact of risk-adjusting cesarean delivery rates when reporting hospital
performance.
AB - CONTEXT: Hospitals and health plans are often ranked on rates of cesarean
delivery, under the assumption that lower rates reflect more appropriate, more
efficient care. However, most rankings do not account for patient factors that
affect the likelihood of cesarean delivery. OBJECTIVE: To compare hospital
cesarean delivery rates before and after adjusting for clinical risk factors that
increase the likelihood of cesarean delivery. DESIGN: Retrospective cohort study.
SETTING: Twenty-one hospitals in northeast Ohio. PATIENTS: A total of 26127 women
without prior cesarean deliveries admitted for labor and delivery from January
1993 through June 1995. MAIN OUTCOME MEASURES: Hospital rankings based on
observed and risk-adjusted cesarean delivery rates. RESULTS: The overall cesarean
delivery rate was 15.9% and varied (P<.001) from 6.3% to 26.5% in individual
hospitals. Adjusted rates varied from 8.4% to 22.0%. The correlation between
unadjusted and adjusted hospital rankings (ie, 1-21) was only modest (R=0.35,
P=.12). Whereas 7 hospitals were classified as outliers (ie, had rates higher or
lower [P<.05] than overall rate) on the basis of both unadjusted and adjusted
rates, outlier status changed for 5 hospitals (24%), including 2 that changed
from outliers to nonoutliers, 2 that changed from nonoutliers to outliers, and 1
that changed from a high outlier to a low outlier. CONCLUSIONS: Cesarean delivery
rates varied across hospitals in a single metropolitan region. However, rankings
that fail to account for clinical factors that increase the risk of cesarean
delivery may be methodologically biased and misleading to the public.
PMID- 9643861
TI - Gastrostomy placement and mortality among hospitalized Medicare beneficiaries.
AB - CONTEXT: Although the use of feeding tubes among older individuals stirs
considerable controversy, population-based descriptive data regarding patient
outcomes are scarce. OBJECTIVE: To describe hospitalized Medicare beneficiaries
having gastrostomies placed and their associated mortality rates. DESIGN:
Retrospective cohort study. SETTING AND PATIENTS: Hospitalized Medicare
beneficiaries aged 65 years or older discharged in 1991 following gastrostomy
placement (excluding individuals in health maintenance organizations). MAIN
OUTCOME MEASURES: Mortality at 30 days, 1 year, and 3 years following gastrostomy
and characteristics of individuals undergoing gastrostomy placement. RESULTS: In
1991, claims reflecting gastrostomy insertion were submitted for 81105 older
Medicare beneficiaries following hospital discharge. The in-hospital mortality
rate was 15.3%. Cerebrovascular disease, neoplasms, fluid and electrolyte
disorders, and aspiration pneumonia were the most common primary diagnoses. The
overall mortality rate at 30 days was 23.9% (95% confidence interval [CI], 23.65%
24.2%), reaching 63.0% (95% CI, 62.7%-63.4%) at 1 year and 81.3% (95% CI, 81.0%
81.5%) by 3 years. One in 131 white and 1 in 58 black Medicare beneficiaries aged
85 years or older was discharged alive or deceased from a hospital in 1991
following gastrostomy placement. CONCLUSIONS: Gastrostomies are frequently placed
in older individuals and more often in blacks; mortality rates following
placement are substantial.
PMID- 9643862
TI - Public health implications of antiretroviral therapy and HIV drug resistance.
AB - Widespread use of antiretroviral agents and increasing occurrence of human
immunodeficiency virus (HIV) strains resistant to these drugs have given rise to
a number of important issues. Some of these concerns are distinct from the
obvious question of the relationship between drug resistance and treatment
failure and have potentially widespread public health implications. The relevant
issues include but are not limited to the following: (1) frequency with which
drug-resistant virus may be transmitted via sexual, intravenous, or mother-to
child routes; (2) ability of drug-resistant variants to be transmitted, a
question that relates, in part, to the relative fitness of such strains; (3)
effectiveness of antiviral therapy in diminishing viral burden in both blood and
genital secretions, and whether this may be compromised in persons harboring
resistant virus; and (4) importance of patient adherence to antiviral therapy and
its relationship to sustained reduction in viral load to minimize the appearance
in and transmission of drug-resistant virus from both blood and genital
secretions. Thus, prevention of both development of HIV drug resistance as well
as transmission of drug-resistant variants is a central issue of public health
importance. Unless this topic is appropriately addressed, the likelihood is that
drug-resistant variants of HIV, if able to successfully replicate, will sustain
the epidemic and limit the effectiveness of antiviral therapy.
PMID- 9643863
TI - Antiretroviral drug resistance testing in adults with HIV infection: implications
for clinical management. International AIDS Society--USA Panel.
AB - OBJECTIVES: To review current knowledge of the biology and clinical implications
of human immunodeficiency virus (HIV) resistance to antiretroviral drugs,
describe assays for measuring resistance, and assess their use in clinical
practice. PARTICIPANTS: The International AIDS Society-USA assembled a panel of
13 physicians with expertise in basic science, clinical research, and patient
care relevant to HIV resistance to antiretroviral drugs. EVIDENCE: We reviewed
available data from published reports and presented at national and international
research conferences. Basic science research, clinical trial results, and expert
opinions were used to form the basis of this report. Data on methods for and
characteristics of specific genotypic and phenotypic assays were obtained from
manufacturers and service providers. CONSENSUS PROCESS: The panel met regularly
between October 1997 and April 1998. Panel subgroups developed and discussed
different sections of the report before discussing them with the entire panel.
Conclusions and suggested approaches to the use of resistance testing were
determined by group consensus. CONCLUSIONS: Plasma HIV RNA level and CD4+ cell
count are the primary values that should be used to guide the initiation of
antiretroviral therapy and subsequent changes in therapy. Possible causes of
treatment failure other than development of drug resistance that should be
considered are adherence, drug potency, and pharmacokinetic issues. Genotypic and
phenotypic testing for HIV resistance to antiretroviral drugs may prove useful
for individual patient management. Assays under development need validation,
standardization, and a clearer definition of their clinical roles. Possible
current roles of resistance testing for choosing an initial regimen or changing
antiretroviral therapy, as well as possible implications of the presence or
absence of phenotypic resistance and genotypic changes, are discussed.
PMID- 9643864
TI - A 24-year-old woman with anorexia nervosa.
PMID- 9643865
TI - A 42-year-old man with hypertension, 1 year later.
PMID- 9643866
TI - A cure for the common cold? Zinc again.
PMID- 9643867
TI - Drug-resistant HIV-1: the virus strikes back.
PMID- 9643868
TI - New treatments for genital warts less than ideal: abstract and commentary.
PMID- 9643869
TI - JAMA patient page: the common cold.
PMID- 9643870
TI - Behavior of heavy metals in human urine and blood following calcium disodium
ethylenediamine tetraacetate injection: observations in metal workers.
AB - To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA)
on the behavior of 8 heavy metals in human urine and blood, CaEDTA was
administered for 1 h by intravenous injection to 18 male metal foundry workers,
whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl.
Significant increases were found in urinary excretion of manganese, chromium,
lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium
excretion reached a maximal level within 1 h after the start of injection, while
urinary manganese, lead, and zinc excretion reached their highest concentrations
between 1 and 2 h. Urinary copper excretion reached the highest level between 2
and 4 h. The rapid increases in urinary excretion of five metals were different
from the "circadian rhythms," which are the normal, daily variations in renal
glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead
concentrations were highest 1.5 h after the start of the 1-h injection, while
plasma zinc concentration became lowest 5 h after the start of CaEDTA injection.
Data suggest that manganese and chromium absorbed in human tissues might be
mobilized by CaEDTA.
PMID- 9643871
TI - Urinary excretion of arsenic metabolites after long-term oral administration of
various arsenic compounds to rats.
AB - The metabolism of arsenic compounds in rats was studied by comparing urinary
metabolites of arsenic compounds administered for 1 wk or 7 mo. Male F344/DuCrj
rats were given 100 mg As/L as monomethylarsonic acid (MMA), dimethylarsinic acid
(DMA), trimethylarsine oxide (TMAO), or arsenobetaine (AsBe), or 10 mg As/L as
arsenite [As(III)] via drinking water for 7 mo. Urine was collected by forced
urination after 1 wk or 7 mo. Arsenic metabolites in urine were analyzed by ion
chromatography with inductively coupled plasma mass spectrometry. In the case of
As(III) ingestion, a small portion of all arsenic excreted in urine (about 6%)
was excreted in inorganic form, while most arsenic was excreted as methylated
arsenic metabolites. Following MMA treatments for 1 wk or 7 mo, the predominant
products excreted were unchanged MMA and DMA accompanied by small amounts of TMAO
and tetramethylarsonium (TeMA). In the case of DMA treatment the urinary
compounds found were mainly the parent DMA and TMAO with minute amounts of TeMA.
TMAO was methylated to TeMA to a slight extent after 1 wk and 7 mo of
administration, although most TMAO was excreted in the form of unchanged TMAO.
AsBe was predominantly eliminated in urine without any transformation. Two
unidentified metabolites were detected in urine after 7 mo of arsenic species
exposure; the amounts of these metabolites increased in the order DMA > MMA >
TMAO with only small quantities of these detected in the As(III)-treated group.
These results suggest that these unidentified metabolites are formed during a
demethylation process, and not during methylation. Our findings indicate that
long-term exposure to As(III), MMA, or DMA decreases the proportion of TMAO
elimination in urine and increases that of DMA, M-1, and M-2, and that further
methylation to TMAO to TeMA does occur to a slight extent following long-term
exposure to arsenical compounds in rats.
PMID- 9643872
TI - Effects of acute inhalation exposure to 1,1,1-trichloroethane on the hypothalamo
pituitary-adrenal axis in male Sprague-Dawley rats.
AB - 1,1,1-Trichloroethane (TRI) is a commonly used industrial solvent with a
considerable potential for inhalation abuse. Previous studies in our laboratory
and elsewhere have shown that this agent exerts a suppressant effect on operant
responding, as well as a number of additional neurobehavioral effects that are
similar to those of central nervous system (CNS) depressant drugs. In an effort
to provide information relevant to potential mechanisms involved in the
behavioral effects and abuse potential of TRI, the present study evaluated the
acute effects of this agent on the activity of the hypothalamo-pituitary-adrenal
(HPA) axis . Male Sprague-Dawley rats were exposed to 3500 or 5000 ppm TRI by
inhalation for 10 or 30 min. Following exposure, plasma levels of
adrenocorticotropic hormone (ACTH) and corticosterone and levels of ACTH and
corticotropin-releasing factor (CRF) in three brain regions--hypothalamus,
hippocampus, and frontal cortex--were determined by selective radioimmunoassays.
Levels of TRI in the three brain regions as well as blood were measured by
headspace gas chromatography to determine the target tissue concentrations
responsible for neuroendocrine changes. Uptake of TRI in blood and all brain
regions was very rapid, with stable concentrations apparently achieved within 10
min and maintained for 30 min. During this time course, a significant decrease in
plasma corticosterone was produced at 30 min but no significant change in plasma
ACTH was observed with 3500 ppm TRI. However, after exposure to 5000 ppm, both
plasma ACTH and plasma corticosterone were significantly reduced at 10 and 30
min. ACTH levels in the three brain regions were not significantly changed by
TRI, while hypothalamic CRF was significantly increased during exposure to 3500
ppm. However, hypothalamic concentrations of CRF declined following 30 min at
3500 ppm and were not significantly changed by 5000 ppm. This complexity of
effects on the regulation of HPA axis activity likely precluded the establishment
of consistent relationships between changes in hormonal levels and blood or
regional brain concentrations of the inhalant. However, these actions of TRI were
strikingly similar to those previously reported for the benzodiazepines.
PMID- 9643873
TI - Metabolism of chloral hydrate in mice and rats after single and multiple doses.
AB - Chloral hydrate is a hepatocarcinogen in mice but not rats. To examine this
species-related difference, male and female B6C3F1 mice and Fischer (F344) rats
were treated by gavage with 1 or 12 doses of chloral hydrate, and concentrations
of the drug and its metabolites were determined in plasma at 0.25, 7, 3, 6, and
24 h and 2, 4, 8, and 16 d after the last treatment. Maximum levels of chloral
hydrate were observed at the initial sampling time of 0.25 h. By 1 h, levels
dropped substantially, and by 3 h, chloral hydrate could not be detected.
Trichloroacetic acid was the major metabolite found in the plasma, with peak
levels being observed 1-6 h after dosing. The concentrations then slowly
decreased such that by 2 d this metabolite could no longer be detected.
Trichloroethanol was assayed as both the free alcohol and its glucuronide.
Maximum levels of trichoroethanol occurred at 0.25 h, and by 1-3 h approached the
limits of detection. A pharmacokinetic model was constructed to describe the
metabolic data. The plasma half-life values of chloral hydrate were similar in
both species. In mice, the rate of elimination of trichloroacetic acid was
significantly increased after multiple doses; this difference was not observed
with rats. The half-life of trichloroethanol and its glucuronide was
significantly greater in rats as compared to mice. None of the metabolic
parameters appears to account for the hepatocarcinogenicity of chloral hydrate
seen in mice but not rats.
PMID- 9643874
TI - Modulation of 7,12-dimethylbenz[a]anthracene disposition and hepatocarcinogenesis
by dieldrin and chlordecone in rainbow trout.
AB - The present study examined whether modified xenobiotic transport, resulting from
chlordecone (CD) or dieldrin pretreatment, would alter polycyclic aromatic
hydrocarbon (PAH) or organochlorine (OC) target organ doses and subsequent tumor
organospecificity or incidence rates in rainbow trout. Additionally, the
potential for exposure to dieldrin or CD, following PAH exposure, to enhance
tumor incidence was assessed. Evaluation of CD pretreatment effects on [14C]CD
disposition in trout was conducted following two i.p. (0-15 mg/kg) and two
dietary (0-0.4 mg/kg/d) pretreatment regimes. To assess the influence of OC
pretreatment on cancer induced by the PAH 7,12-dimethylbenz[a]anthracene (DMBA),
juvenile trout were fed control, CD (0.1, 0.4 mg/kg/d), or dieldrin (0.1, 0.3
mg/kg/d) diets for 9 wk, received a waterborne [3H]DMBA exposure (1 mg/L, 20 h),
and resumed control, CD, or dieldrin diets for 33 wk. [3H]DMBA disposition and
hepatic [3H]DMBA binding were examined immediately and 24 h after exposure.
Hepatic and stomach tumor incidences were determined 33 wk after DMBA exposure.
CD pretreatment did not influence [14C]CD or [3H]DMBA hepatic concentrations,
hepatic [3H]DMBA DNA binding, or hepatic/stomach tumor incidence. It did,
however, elevate bile [14C]CD and [3H]DMBA concentrations. Postinitiation
exposure to CD weakly enhanced DMBA-induced hepatic tumor incidence at the low
but not the high CD dose. Dieldrin pretreatment did not influence stomach
[3H]DMBA equivalents or stomach tumor incidence but did cause an elevation in
biliary and hepatic concentrations of [3H]DMBA equivalents. [3H]DMBA binding to
liver DNA was significantly increased and hepatic tumor incidence was elevated by
dieldrin pretreatment. Dieldrin treatment following DMBA initiation did not
enhance hepatic or stomach tumor incidence. Ecoepidemiology studies, to date,
have reported correlations between the co-occurrence of PAHs and OCs and elevated
tumor incidence in feral fish, but cause-and-effect relationships have been
difficult to establish. The results of the present study confirm that OCs, such
as dieldrin and CD, play a role in modifying PAH-induced carcinogenesis in fish.
PMID- 9643875
TI - [Reconstruction of the ossicular chain].
PMID- 9643876
TI - Teaching caring attitudes.
PMID- 9643877
TI - What makes a good doctor: defining the ideal end-product of medical education.
PMID- 9643878
TI - A long-term collaborative approach to identifying future physicians.
PMID- 9643879
TI - Caring for pregnant adolescents.
PMID- 9643880
TI - Teaching residents about child abuse and neglect.
PMID- 9643881
TI - Using electronic journal writing to foster reflection and provide feedback in an
introduction to clinical medicine.
PMID- 9643882
TI - Reinforcement of self-directed learning and the development of professional
attitudes through peer- and self-assessment.
PMID- 9643883
TI - Teaching professionalism through tutorial discussions of literature--stories,
poems, and essays.
PMID- 9643884
TI - Developing skills in promoting effective behavioral change.
PMID- 9643885
TI - Facilitating interns' self-assessment.
PMID- 9643886
TI - A student-planned memorial service.
PMID- 9643887
TI - A palliative care survey to measure medical students' and health care
professionals' knowledge and attitudes.
PMID- 9643888
TI - Collaborative development of geriatric education modules for resident education.
PMID- 9643889
TI - Innovation in an undergraduate geriatrics program.
PMID- 9643891
TI - A fourth-year elective in medical education.
PMID- 9643890
TI - Use of behavioral descriptors for performance evaluation in first- and second
year clinical experiences.
PMID- 9643892
TI - A first-year minicurriculum on TIA/stroke.
PMID- 9643893
TI - Determination of third-year student exposure to and participation in learning
objectives.
PMID- 9643894
TI - Using patients to teach functional assessment of patients with arthritis.
PMID- 9643895
TI - Focusing attention on critical elements of the pediatrics clerkship.
PMID- 9643896
TI - Qualitative analysis of student-generated learning issues to assess content
coverage in problem-based learning.
PMID- 9643897
TI - A unit-mastery program in an ambulatory care internal medicine clerkship.
PMID- 9643898
TI - A core anatomy program for the undergraduate medical curriculum.
PMID- 9643899
TI - Use of structured student-facilitated small groups in a behavioral
science/psychiatry course.
PMID- 9643900
TI - A program to create and exchange teaching cases in radiology.
PMID- 9643901
TI - An introduction to complementary healing practices.
PMID- 9643902
TI - Improving communication and interviewing skills: a community-based approach.
PMID- 9643903
TI - Teaching motivational interviewing to first-year students.
PMID- 9643904
TI - Improving fourth-year students' complex interviewing skills.
PMID- 9643905
TI - Group review in differential diagnosis.
PMID- 9643906
TI - Using standardized patients to teach and learn psychotherapy.
PMID- 9643907
TI - A crisis management program for residents in anesthesia.
PMID- 9643908
TI - Using simulation to train residents in managing critical events.
PMID- 9643909
TI - Flexible sigmoidoscopy training program for internal medicine residents.
PMID- 9643911
TI - PRIME: preparing first-year medical students for an intensive clinical
experience. The Generalist Coordinating Council.
PMID- 9643910
TI - Case snapshots: a new tool for morning report.
PMID- 9643912
TI - The first three days of residency: an efficient introduction to clinical
medicine.
PMID- 9643913
TI - The use of a virtual reality haptic device in surgical training.
PMID- 9643914
TI - An interdisciplinary clinical performance examination for a third-year combined
medicine-surgery clerkship.
PMID- 9643915
TI - Global ratings versus checklist scoring in an OSCE.
PMID- 9643916
TI - A community pediatrics/public health rotation for pediatric residents.
PMID- 9643917
TI - Using rural training tracks to encourage rural practice careers and enhance
training in family medicine.
PMID- 9643918
TI - Integrating public health issues and community health care delivery.
PMID- 9643919
TI - A fellowship in the population-centered clinical method.
PMID- 9643920
TI - Using videoconferencing of a live surgery to teach about pelvic anatomy.
PMID- 9643921
TI - A library-based information skills rotation for internal medicine residents.
PMID- 9643922
TI - Teaching cross-cultural medicine and international health at home.
PMID- 9643923
TI - Using palm-top computers to improve students' evidence-based decision making.
PMID- 9643924
TI - Enhancing medical students' participation in the rural community.
PMID- 9643925
TI - Shared learning between medical, dental, nursing, and therapy undergraduates.
PMID- 9643926
TI - Learning medicine in the community.
PMID- 9643927
TI - VA Women's Health Center as an ambulatory training site.
PMID- 9643928
TI - Integrating technology into resident and student curricula.
PMID- 9643929
TI - Inclusion of allied health students in a problem-based learning course.
PMID- 9643930
TI - A multidisciplinary interclerkship on hunger and malnutrition.
PMID- 9643931
TI - Interactive instruction technology in graduate medical education.
PMID- 9643932
TI - Using a combined CME course to improve physicians' skills in eliciting patient
adherence.
PMID- 9643933
TI - Skills for internship.
PMID- 9643934
TI - Integration of self-directed computerized patient simulations into the internal
medicine ambulatory clerkship.
PMID- 9643935
TI - Using standardized medical students to improve junior faculty teaching.
PMID- 9643936
TI - A distance-learning program for telemedicine presenters.
PMID- 9643937
TI - A certificate in medical management for physicians.
PMID- 9643938
TI - Using a comprehensive handbook and individualized orientation plan for faculty
development in a decentralized academic department.
PMID- 9643939
TI - Validating a global measure of faculty teaching performance.
PMID- 9643940
TI - Promoting small-group teaching through funding changes.
PMID- 9643941
TI - General Clinical Research Center Scholars Program.
PMID- 9643942
TI - Using videoconferencing to train community family medicine preceptors.
PMID- 9643943
TI - Integrating information technology training into an established faculty
development program.
PMID- 9643944
TI - A teaching skills workshop for community preceptors.
PMID- 9643945
TI - An intramural grants program for developing medical school curricula.
PMID- 9643946
TI - Challenges in the Study of Encephalomyopathies of Mitochondrial Origin.
Proceedings of a conference. Philadelphia, Pennsylvania, USA. 4-7 April 1997.
PMID- 9643947
TI - Methods development for epidemiologic investigations of the health effects of
prolonged ozone exposure. Part II. An approach to retrospective estimation of
lifetime ozone exposure using a questionnaire and ambient monitoring data
(California sites).
AB - An extensive body of data supports a relation between acute exposures to ambient
ozone and the occurrence of various acute respiratory symptoms and changes in
measures of lung function. In contrast, relatively few data are available on the
human health effects that result from long-term exposure to ambient ozone,
Current efforts to study long-term ozone-related health effects are limited by
the methods available for ascertaining lifetime exposures to ozone. The present
feasibility study was undertaken as part of the Health Effects Institute's
Environmental Epidemiology Planning Project (Health Effects Institute 1994) to
(1) determine whether, in the context of an epidemiologic study, reliable
estimates can be obtained for lifetime exposures to ozone by combining estimates
from lifetime residential histories, typical activity patterns during life, and
residence-specific ambient ozone monitoring data; (2) identify the minimum data
required to produce reliable estimates of lifetime exposure; and (3) analyze the
relations between various estimates of lifetime ozone exposure and measures of
lung function. A convenience sample of 175 first-year students at the University
of California, Berkeley, who lived all of their lives in selected areas of
California (the Los Angeles Basin or the San Francisco Bay Area), were studied on
two occasions (test and retest or test sessions 1 and 2), five to seven days
apart. Residential and lifestyle data were obtained from a questionnaire:
residence-based ambient ozone exposure values were assigned by interpolation of
ambient ozone monitoring data to residential locations. Estimated lifetime
exposure was based on average ozone levels between 10 a.m. and 6 p.m. and hours
of exposure to ozone concentrations greater than 60 parts per billion (ppb).
"Effective" lifetime exposure to ozone was based on a weighted average of
estimated time spent in different ambient ozone environments as determined by
different combinations of activity data. Pulmonary function was evaluated with
flows and volumes from maximum expiratory flow-volume curves and slope of phase
III of the single-breath nitrogen washout (SBNW) curves. Although the test-retest
reliability of the residential history was acceptably high only for first and
second residences, most of the unreliability for other residences came from
residences occupied for relatively short durations. Therefore, the test-retest
reliability of estimated lifetime exposure to ozone was high, with intraclass
correlations greater than 0.90 for all approaches evaluated. Multiple, linear
regression analyses showed a consistently negative relation between estimates of
lifetime exposure to ozone and flows that reflect the physiology of pulmonary
small airways. No relation was observed between lifetime ozone exposure and
forced expiratory volume or the slope of phase III, and the relation between
lifetime exposure and forced expiratory volume in one second was inconsistent.
The results of the flow measures were unaffected by the method used to estimate
lifetime exposure and gave effect estimates that were nearly identical. The data
from this study indicate that useful and reproducible estimates of lifetime ozone
exposure can be obtained in epidemiologic studies by using a residential history.
However, the total burden of ozone to which the subjects were exposed cannot be
determined accurately from such data. Nonetheless, the estimates so obtained
appear to be associated with alterations in pulmonary function that are
consistent with the predicted site of maximum effect of ozone in the human lung.
PMID- 9643948
TI - Methods development for epidemiologic investigations of the health effects of
prolonged ozone exposure. Part III. An approach to retrospective estimation of
lifetime ozone exposure using a questionnaire and ambient monitoring data (U.S.
sites).
AB - Methods are needed for retrospective estimation of long-term ozone exposures in
epidemiologic studies. The overall objective of this study was to evaluate
whether data from available U.S. ozone monitoring sites are useful for estimating
lifetime ozone exposures of young adults (for example, college students). Several
aspects of this question were evaluated. First, we applied and (compared several
spatial interpolation methods to a set of long-term average ozone data from all
U.S. monitoring sites in operation from 1981 through 1990. Interpolation methods
included simple and weighted averages, linear regression, and, in an exploratory
way, kriging. The comparison of methods was carried out for five different
metrics of ozone concentration: the daily one-hour maximum (MAX1) and eight-hour
maximum (MAX8), the average ozone concentrations between 10 a.m. and 6 p.m.
(MID8) and between 10 a.m. and 10 p.m. (MID12), and the sum of all hourly ozone
concentrations greater than or equal to 60 parts per billion (ppb) (SUM06). We
also tested whether interpolations were improved by modeling the influence of
covariates such as population density, elevation, and weather on ozone
concentrations. We analyzed the reliability of a set of newly developed questions
about past activity levels among a group of 52 freshmen students at Yale
University. This was done by analyzing the agreement between answers to the same
questionnaire administered two times, one month apart (test and retest), to the
same students. Finally, we combined the interpolation models with residential
history information obtained by questionnaire to derive long-term ozone exposure
estimates for a group of 200 Yale freshmen. Results of our study showed that the
density of available monitoring sites appears to be adequate for estimating
spatial patterns of long-term average ambient ozone concentrations. A simple
regression-based interpolation on the three nearest sites produced consistently
good results. Including covariates in the interpolation models did not
substantially improve the estimates. The largest estimation errors occurred for
areas where ozone concentrations were highest. The newly developed activity
history questions exhibited fair to moderate reliability, The results of this
work imply that reasonably precise estimates of long-term ambient ozone
concentrations for use in large-scale epidemiologic studies can be achieved by
interpolating ozone concentrations between available U.S. monitoring sites. This
study did not address the issues of whether and how retrospective data on factors
that modify exposure or dose (e.g., indoor/outdoor penetration of ozone and time
outdoors) can be used to derive estimates of long-term personal ozone exposures
and contribute to the assessment of received dose.
PMID- 9643950
TI - Sebaceous gland, acne and related disorders--an epilogue.
PMID- 9643951
TI - Sebaceous gland, acne and related disorders. basic and clinical research,
clinical entities and treatment. Proceedings of the 4th International Dermatology
Symposium. Berlin, April 11-13, 1997.
PMID- 9643949
TI - Wanderlust kinetics and variable Ca(2+)-sensitivity of dSlo [correction of
Drosophila], a large conductance CA(2+)-activated K+ channel, expressed in
oocytes.
AB - Cloned large conductance Ca2+-activated K+ channels (BK or maxi-K+ channels) from
Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised
membrane patches with the patch-clamp technique. Both a natural variant and a
mutant that eliminated a putative cyclic AMP-dependent protein kinase
phosphorylation site exhibited large, slow fluctuations in open probability with
time. These fluctuations, termed "wanderlust kinetics," occurred with a time
course of tens of seconds to minutes and had kinetic properties inconsistent with
simple gating models. Wanderlust kinetics was still observed in the presence of
5mM caffeine or 50 nM thapsigargin, or when the Ca2+ buffering capacity of the
solution was increased by the addition of 5 mM HEDTA, suggesting that the
wanderlust kinetics did not arise from Ca2+ release from caffeine and
thapsigargin sensitive internal stores in the excised patch. The slow changes in
kinetics associated with wanderlust kinetics could be generated with a discrete
state Markov model with transitions among three or more kinetic modes with
different levels of open probability. To average out the wanderlust kinetics,
large amounts of data were analyzed and demonstrated up to a threefold difference
in the [Ca2+]i required for an open probability of 0.5 among channels expressed
from the same injected mRNA. These findings indicate that cloned dSlo channels in
excised patches from Xenopus oocytes can exhibit large variability in gating
properties, both within a single channel and among channels.
PMID- 9643952
TI - Organ transplantation from donor who died of cyanide poisoning: a case report.
AB - Shortage of donor organs has become on of the most important limiting factors in
the field of transplantation. Suitability of organs from patients dying from
poisoning is an unexplored area. This is because of the suspicion that the
organs, in particular the liver and the kidneys, might have been irreversibly
damaged by the poison. We report a case of cyanide poisoning in which the kidneys
and corneas were harvested after the level of poison fell to below lethal
concentration. These organs were later transplanted without any evidence of
adverse effects at follow-up.
PMID- 9643953
TI - Polarity of meiotic recombination in the bronze locus of maize.
PMID- 9643954
TI - Israel bans import of sildenafil citrate after six deaths in the US.
PMID- 9643955
TI - Prostate cancer screening reduces deaths.
PMID- 9643956
TI - Are sex and death related? Study did not treat sexual behaviour with the
importance it deserves.
PMID- 9643957
TI - Cancer in the offspring of radiation workers. Exposure to internal radioisotopes
may be responsible.
PMID- 9643958
TI - Cancer in the offspring of radiation workers. Combination of antibiotics and non
fatal infections may be responsible for higher number of deaths from leukemia.
PMID- 9643959
TI - Cognitive impairment and survival in very elderly people. Decreased survival with
cognitive impairment seems not be related to comorbidity.
PMID- 9643960
TI - Effect of moderate alcohol consumption on Lp(a) lipoprotein concentrations. No
effect seen in Australian drinkers.
PMID- 9643961
TI - Effect of moderate alcohol consumption on Lp(a) lipoprotein concentrations.
Reduction is not found in women.
PMID- 9643962
TI - Interventions to treat shoulder pain. Lack of concordance between rheumatologists
may render multicentre studies invalid.
PMID- 9643964
TI - Proceedings of the International Ion Chromatography Symposium 1997. Santa Clara,
California, USA. 14-17 September 1997.
PMID- 9643963
TI - IBC Conference on Engineered Animal Models: Advances and Applications,
Washington, DC, USA, 22-23 September 1997.
PMID- 9643965
TI - Duplicate publication.
PMID- 9643966
TI - The effect of suspending solution supplemented with marine cations on the
oxidation of Biolog GN MicroPlate substrates by Vibrionaceae bacteria.
AB - Bacteria belonging to the family Vibrionaceae were suspended using saline and a
solution prepared from a marine-cations supplement. The effect of this on the
profile of oxidized substrates obtained when using Biolog GN MicroPlates was
investigated. Thirty-nine species belonging to the genera Aeromonas, Listonella,
Photobacterium, and Vibrio were studied. Of the strains studied, species of
Listonella, Photobacterium, and Vibrio could be expected to benefit from a marine
cations supplement that contained Na+, K+, and Mg2+. Bacteria that are not of
marine origin are usually suspended in normal saline. Of the 39 species examined,
9 were not included in the Biolog data base and were not identified. Of the 30
remaining species, 50% were identified correctly using either of the suspending
solutions. A further 20% were correctly identified only when suspended in saline.
Three species, or 10%, were correctly identified only after suspension in the
marine-cations supplemented solution. The remaining 20% of species were not
correctly identified by either method. Generally, more substrates were oxidized
when the bacteria had been suspended in the more complex salts solution. Usually,
when identifications were incorrect, the use of the marine-cations supplemented
suspending solution had resulted in many more substrates being oxidized. Based on
these results, it would be preferable to use saline to suspend the cells when
using Biolog for identification of species of Vibrionaceae. A salts solution
containing a marine-cations supplement would be preferable for environmental
studies where the objective is to determine profiles of substrates that the
bacteria have the potential to oxidize. If identifications are done using marine
cations supplemented suspending solution, it would be advisable to include
reference cultures to determine the effect of the supplement. Of the Vibrio and
Listonella species associated with human clinical specimens, 8 out of the 11
studied were identified correctly when either of the suspending solutions was
used.
PMID- 9643967
TI - Retraction: An endo-beta-1,4-glucanase gene (celA) from the rumen anaerobe
Ruminococcus albus 8: cloning, sequencing, and transcriptional analysis.
PMID- 9643968
TI - Rapid method for the detection of genetically engineered microorganisms by
polymerase chain reaction from soil and sediments.
AB - A rapid and sensitive method for the detection of genetically engineered
microorganisms in soil and sediments has been devised by in vitro amplification
of the target DNAs by a polymerase chain reaction. A cloned catechol 2,3
dioxygenase gene located on the recombinant plasmid pOH101 was transferred to
Pseudomonas putida MMB2442 by triparental crossing and used as a target organism.
For the polymerase chain reaction from soil and sediment samples, the template
DNA was released from a 100-mg soil sample. Bacterial seeded soil samples were
washed with Tris-EDTA buffer (pH 8.0) and treated with a detergent lysis solution
at 100 degrees C. After addition of 1% polyvinylpolypyrrolidine solution, the
samples were boiled for 5 min. Supernatant containing nucleic acid was purified
with a PCR purification kit. The purified DNA was subjected to polymerase chain
reaction, using two specific primers designed for the amplification of catechol
2,3-dioxygenase gene sequences. The detection limit was 10(2) cells per gram of
soil. This method is rapid and obviates the need for lengthy DNA purification
from soil samples.
PMID- 9643969
TI - UCSD Mitochondrial Medicine Conference. San Diego, California, USA. February 19
21, 1998.
PMID- 9643970
TI - Tumor hypoxia: the role of nuclear medicine.
PMID- 9643971
TI - Radiation doses deriving from patients undergoing 111In-DTPA-D-Phe-1-octreotide
scintigraphy.
PMID- 9643972
TI - Radiation dose to technicians for nuclear medicine procedures.
PMID- 9643973
TI - Dose contribution from iron-55 as a daughter radionuclide of cobalt-55.
PMID- 9643974
TI - Cardiac dysfunction in cancer patients receiving paclitaxel.
PMID- 9643975
TI - Chemotherapy and uptake of technetium-99m sestamibi in breast cancer.
PMID- 9643976
TI - Modulation of the Immune Response to Vaccine Antigens. Proceedings of a
conference. Bergen, Norway, June 18-21, 1996.
PMID- 9643977
TI - Amplification of the translocated c-myc genes in three Burkitt lymphoma cell
lines.
AB - Translocations of the coding exons of the human c-myc gene are consistent
features of human Burkitt lymphomas (BL). In the BL cell lines CA46, JD40, and
ST486, the second and third c-myc exons have been translocated into the
immunoglobulin heavy chain locus. In addition to this rearrangement, in all three
cell lines, we have found that the translocated c-myc exons show low-level
amplification relative to restriction fragments from the germ-line c-myc gene.
The patterns of hybridization of an IgM switch region probe suggest that
immunoglobulin heavy chain sequences have been co-amplified with the translocated
c-myc sequences. Differential sedimentation was used to determine whether the
amplified sequences reside in high-molecular-weight chromosomes or low-molecular
weight extrachromosomal DNA. In JD40 and ST486 cells, the amplified c-myc
sequences were found on high-molecular-weight chromosomes ST486 cells also
contained translocated C-myc sequences in low-molecular-weight, extrachromosomal
DNA, as did CA46 cells. These conclusions were corroborated by fluorescence in
situ hybridization (FISH) of HeLa, CA46, ST486 and JD40 metaphase chromosomes.
These results suggest that there is ongoing selection for cells containing
amplified copies of the expressed c-myc sequences. and that there is continuous
generation of extrachromosomal copies of the translocated c-myc sequences in
ST486 and CA46 cells.
PMID- 9643978
TI - Properties of exgS, a gene for a major subunit of the Clostridium cellulovorans
cellulosome.
AB - The nucleotide sequence of P70, one of the three major subunits of the
Clostridium cellulovorans cellulosome, has been determined. The gene designated
as exgS (Genbank Accession No. U34793) consists of 2112 bp and encodes a protein
containing 703 amino acids with a molecular mass of 77.7 kDa. ExgS has a putative
signal peptide sequence of 32 amino acids. The N-terminal region is separated
from the C-terminal region by a short-Pro-Thr-Pro linker. The C-terminal region
of ExgS contains a duplicated sequence (DS), each sequence consisting of 22 amino
acids. exgS, located 67 bp downstream of cbpA in the chromosome, is immediately
upstream of a gene encoding a family 9 type endoglucanase that we have designated
as EngH. This gene cluster to date consists of regA-cbpA-exgS-engH. Recombinant
ExgS (rExgS) containing no signal peptide was expressed in E. coli. The rExgS
actively digested several forms of cellulose, including Avicel, Sigmacell101,
crystalline cellulose, and xylan, but not carboxymethyl cellulose (CMC).
Cellotetraose was the smallest oligosaccharide substrate for rExgS. The enzymatic
studies indicated that ExgS was an exoglucanase and had some properties similar
to that of CelS from C. thermocellum and CelF from C.cellulolyticum. An
exoglucanase has now been found to be a component of the C. cellulovorans
cellulosome as well as the previously reported endoglucanases.
PMID- 9643979
TI - [Retrospective analysis of the relationship between HUS incidence and antibiotics
among patients with Escherichia coli O157 enterocolitis in the Sakai outbreak].
AB - An outbreak of Escherichia coli O157:H7 infection occurred in July 1996 in Sakai
City. About 5000 children were infected, 122 of whom developed hemolytic uremic
syndrome (HUS). In this outbreak, almost all patients were administrated some
type of antibiotics. The effects of antibiotics on E. coli O157 associated
hemorrhagic colitis (HC) have been controversial. In this study, we focused on
the effects of antibiotics on development of HUS in the HUS in the Sakai
outbreak. We retrospectively determined the antibiotics administrated within
three days after the onset of HC, clinical courses, and laboratory data of 301
patients who were hospitalized and identified as Escherichia coli O157 infection
by stool culture, from results of questionnaires sent by the Osaka Prefecture
Medical Association to hospitals in Osaka Prefecture. The antibiotics used could
be identified for 216 patients. The incidence of HUS among these patients was
11.6%. They were divided into 19 groups based on the type of antibiotics
administrated. The incidence of HUS in the new quinolone (3.7%) group was low,
but was high in the intravenous cephalosporin (18.2%) group. The differences in
the incidence of HUS among the 19 antibiotic groups was significant (p < 0.05) on
analysis of covariance which eliminated the contributions of variables including
age, sex and laboratory data. These findings indicate that the suitable
antibiotics can prevent the development of E. coli O157-associated HUS.
PMID- 9643980
TI - [Myelodysplastic syndrome and cancer].
PMID- 9643981
TI - The Trypanosome Surface. Proceedings of the Francqui Colloquium on the Expression
and Function of Surface Proteins in Trypanosoma Brucei. Brussels, May 1997.
PMID- 9643983
TI - "The slow code".
PMID- 9643982
TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 20-1998. A 53-year-old man with cardiac amyloidosis and a left
pulmonary mass.
PMID- 9643984
TI - "The slow code".
PMID- 9643985
TI - "The slow code".
PMID- 9643986
TI - "The slow code".
PMID- 9643987
TI - "The slow code".
PMID- 9643988
TI - "The slow code".
PMID- 9643989
TI - Treatment of paraphilia with an analogue of gonadotropin-releasing hormone.
PMID- 9643990
TI - Treatment of paraphilia with an analogue of gonadotropin-releasing hormone.
PMID- 9643991
TI - Preemptive liver transplantation from a living related donor for primary
hyperoxaluria type I.
PMID- 9643992
TI - The response of early gastric cancer to proton-pump inhibitors.
PMID- 9643993
TI - Case 5-1998: bone marrow blasts in chronic myelomonocytic leukemia.
PMID- 9643994
TI - Clinical problem-solving: a square peg in a round hole.
PMID- 9643995
TI - Clinical problem-solving: a square peg in a round hole.
PMID- 9643996
TI - Clinical problem-solving: a square peg in a round hole.
PMID- 9643997
TI - Clinical problem-solving: a square peg in a round hole.
PMID- 9643998
TI - Ephedrine is not phenylephrine.
PMID- 9644000
TI - [AIDS epidemic in Kaliningrad].
PMID- 9643999
TI - More on varicella immunization.
PMID- 9644001
TI - [Older women with AIDS].
PMID- 9644002
TI - [Discontinuation of Act Up!].
PMID- 9644003
TI - [Placebos as AIDS therapy, continued].
PMID- 9644004
TI - [Live attenuated AIDS vaccine possibly lethal].
PMID- 9644005
TI - [Anglo-Saxon guidelines for the treatment of community-acquired pneumonia also
applicable in The Netherlands].
PMID- 9644006
TI - Being heard.
PMID- 9644007
TI - Trading places.
PMID- 9644008
TI - UV-DNA damage in mouse and human cells induces the expression of tumor necrosis
factor alpha.
AB - Ultraviolet light induces the expression of tumor necrosis factor alpha (TNF
alpha) in many mammalian cells. We have examined the signal for this induction in
a human DNA repair-deficient cell line carrying a transgene composed of the
murine TNF regulatory sequences fused to the chloramphenicol acetyltransferase
(CAT) structural gene. When compared by fluence, UVC was a more efficient inducer
of CAT than was UVB, but they were equivalent inducers when compared by the
frequency of cyclobutyl pyrimidine dimers produced by each source. Further,
treatment of UV-irradiated cells with the prokaryotic DNA repair enzyme T4
endonuclease V increased the level of repair of dimers and concomitantly reduced
CAT gene expression. Membrane-bound TNF alpha expression was increased by UV and
reduced by repair of dimers. Finally, in the TNFcat transgene system, DNA damage
directly to the cell with the transgene was required as cocultivation of
unirradiated TNFcat cells with UV-irradiated cells did not increase CAT activity.
These results show that DNA damage is a signal for the induction of TNF alpha
gene expression in mouse and human cells.
PMID- 9644009
TI - Culturing new life.
PMID- 9644010
TI - The prevention pill.
PMID- 9644011
TI - Alcohol in the western world.
PMID- 9644012
TI - It's not rocket science--but it can save lives.
PMID- 9644013
TI - NIH plans bioengineering initiative.
PMID- 9644014
TI - New rules on human subjects could end debate in Canada.
PMID- 9644015
TI - Tau protein mutations confirmed as neuron killers.
PMID- 9644016
TI - Old, old skull has a new look.
PMID- 9644017
TI - One-eyed animals implicate cholesterol in development.
PMID- 9644018
TI - Shotgun sequencing of the human genome.
PMID- 9644019
TI - Deuteronomy?: a puzzle of deuterium and oxygen on Mars.
PMID- 9644020
TI - Glutamate receptor activation: a four-step program.
PMID- 9644022
TI - Proceedings of the University of Colorado Cancer Center Conference: Recent
Developments and Future Directions in the Research and Management of Anorexia and
Cachexia. Cancun, Mexico, October 23-25, 1997.
PMID- 9644021
TI - Circadian rhythms. An end in the beginning.
PMID- 9644023
TI - Annual Congress of the Neurology Association of South Africa. Rustenburg, North
West, 11-14 March 1998. Abstracts.
PMID- 9644024
TI - [Salmonella dublin in cattle].
PMID- 9644025
TI - [In certain publications, the main author, A. Jendryczko is suspected of
plagiarism].
PMID- 9644026
TI - [In response to correspondence from 27.12.1997, the editors are informed that the
article in question was based on collected material from the Gynecologic Clinic
II in the years 1990-1991].
PMID- 9644027
TI - [In this situation, my opinion concerning the identification of an article which
I co-authored as plagiarism is that it is wrong and groundless].
PMID- 9644028
TI - [My explanation concerning the situation regarding articles identified as
plagiarism].
PMID- 9644030
TI - Fever of unknown origin and anemia with Rhodococcus equi infection in an
immunocompetent patient.
PMID- 9644029
TI - Male infertility and the genetics of spermatogenesis.
PMID- 9644031
TI - Gelatinase B modulates selective opening of the blood-brain barrier during
inflammation.
AB - Matrix metalloproteinases (MMPs) are associated with neuroinflammatory diseases,
and blood-brain barrier damage is a pathophysiological consequence of central
nervous system inflammation. We examined whether an increase in MMP production is
coupled with the breakdown of blood-brain barrier integrity in the
lipopolysaccharide (LPS)-injured brain. Rat brain stimulated with LPS showed a
significant rise in gelatinase B (MMP-9) production at 24 h compared with either
tumor necrosis factor-alpha (TNF-alpha) or saline-injected controls. Latent 92
kDa gelatinase B was detected by 4 h, peaked at 8 h, and persisted for 24 h after
LPS injection. Production of the active 84-kDa form of gelatinase B was less
pronounced, but paralleled 92-kDa enzyme expression. Breakdown in blood-brain
barrier integrity, measured by the infiltration of radiolabeled exogenous markers
into the brain, was significant to [14C]sucrose (molecular mass 342 Da) and
injected animals compared with saline-injected controls. The extent of MMP
involvement in barrier permeability was examined in animals treated with the MMP
inhibitor BB-1101. A significant drop in gelatinase A and B production was
detected in LPS-injured animals receiving BB-1101 compared with untreated
animals. This MMP inhibitor also reduced [14C]sucrose uptake in LPS-injected
animals, but had no effect on [14C]dextran uptake. MMP production is upregulated
in LPS-injured brain tissue and is instrumental in regulating the size
differentiated opening of the blood-brain barrier during acute neuroinflammation.
PMID- 9644032
TI - Mechanisms of the antidiabetic effects of the beta 3-adrenergic agonist CL-316243
in obese Zucker-ZDF rats.
AB - Previous studies have demonstrated that chronic cold exposure activates the
sympathetic nervous system, increases energy expenditure, improves glucose uptake
in peripheral tissues [brown and white adipose tissues (BAT and WAT) and muscles]
of normal rats. The goal of the present studies was to test whether the selective
beta 3-adrenergic agonist CL-316243 (CL) would mimic the beneficial beneficial
effects of cold exposure in lean and obese ZDF/Gmi-fa male (ZDF) rats, a new
model of type II diabetes. In obese ZDF rats, chronic infusion of CL (1 mg.kg
1.day-1 for 14 days) significantly decreased body weight gain, food intake, and
WAT weight. It also increased total tissue cytochrome oxidase activity, not only
in BAT (15 times), but also in WAT (2-4) times, suggesting that it progressively
enhanced mitochondriogenesis in adipose tissues. CL treatment normalized
hyperglycemia and reduced hyperinsulinemia and circulating free fatty acid (FFA)
levels. It also improved glucose tolerance and reduced insulin response during an
intravenous glucose tolerance test. In general, the beneficial effects of CL were
more pronounced in obese than in lean rats. Hyperinsulinemic-euglycemic glucose
clamps combined with the [2-3H]deoxyglucose method revealed that CL markedly
improved insulin responsiveness in obese rats (3-4 times) and increased glucose
uptake in BAT (21 times), WAT (3 times), skeletal muscles (2-3 times), and in the
diaphragm (2.8 times), but not in the heart. It is concluded that chronic CL
treatment improves glucose tolerance and insulin responsiveness in obese ZDF rats
by a mechanism similar to that induced by chronic cold exposure, i.e., by
stimulating facultative thermaogenesis, mitochondriogenesis, and glucose
utilization in BAT and WAT. In addition to this mechanism, the reduction in
plasma FFA levels induced by chronic CL treatment may further contribute to
enhance glucose uptake in skeletal muscles (a tissue that does not express
typical beta 3-adrenoceptors) via the "glucose-fatty acid" cycle. The antiobesity
and antidiabetic properties of CL suggest that selective beta 3-adrenergic
agonists may represent useful agents for the treatment of type II diabetes.
PMID- 9644033
TI - Rat trehalase: cDNA cloning and mRNA expression in adult rat tissues and during
intestinal ontogeny.
AB - A partial rat trehalase cDNA has been cloned and used to examine trehalase mRNA
expression. Northern blotting with total RNA from 11 adult rat tissues showed a
trehalase transcript only in small intestine, where it was abundant in proximal
regions but declined steeply toward the ileum. During development, trehalase mRNA
was not detectable in jejunum until postnatal day 19 and then increased markedly
through day 25. Modest levels in trehalase mRNA were induced precociously by
administration of dexamethasone, with increasing responsiveness evident between
the first and second postnatal weeks. In contrast, analysis of sucrase-isomaltase
mRNA on the same blots showed maximal induction at both ages. In adrenalectomized
animals, the ontogenic increase of trehalase mRNA began as usual but proceeded
more slowly than in control animals. Overall, trehalase mRNA expression in the
rat displayed both similarities and differences compared with rabbit. Moreover,
the differences revealed in glucocorticoid responsiveness of trehalase mRNA and
sucrase-isomaltase mRNA suggest that the actions of these hormones on the
developing intestine may be more complex than previously recognized.
PMID- 9644034
TI - Effect of renal interstitial adenosine infusion on phosphate excretion in
diabetes mellitus rats.
AB - We previously demonstrated an increased sensitivity of the renal vasculature to
adenosine (ADO) mediated via ADO A1 receptors in streptozotocin (STZ) diabetic
rats. Because ADO stimulates P(i) reabsorption in the proximal tubule, the
present study was performed to determine whether the sensitivity of the renal
tubular system to the antiphosphaturic effect of ADO is enhanced in STZ rats.
Clearance studies were performed, and ADO was infused into the renal interstitium
via implanted matrices in STZ- and control (Con) rats to mimic the effects of
endogenous ADO. Renal phosphate excretion was significantly increased in STZ rats
(0.75 +/- 0.05 mumol/24 h) compared with Con rats (0.35 +/- 0.08 mumol/24 h), and
fractional phosphate excretion (FEPi) tended to be higher in STZ rats (34.8 +/-
4.1%) than in Con rats (26.7 +/- 2.2%). Renal interstitial ADO infusion (5
mumol/h) was significantly more antiphosphaturic in STZ rats (FEPi decreased by
2.90 +/- 1.6%; P > 0.05), in which ADO only tended to decrease FEPi. To determine
the role of ADO A1 receptors on P(i) excretion, the selective ADO A1 receptor
blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was infused into the renal
interstitium. DPCPX increased FEPi by 4.3 +/- 1.2% (P < 0.05) in the presence and
7.1 +/- 3.9% (P < 0.05) in the absence of ADO infusion in Con rats but had no
effect on FEPi in STZ rats. In conclusion, STZ-diabetes mellitus enhances the
antiphosphaturic effect of ADO by mechanisms unrelated to ADO A1 receptor
stimulation.
PMID- 9644035
TI - Duodenal nutrient exposure elicits nutrient-specific gut motility and vagal
afferent signals in rat.
AB - Volume and chemical characteristics of meals in the gut have been proposed to
generate vagal afferent signals that mediate the negative feedback control of
ingestion and gastric emptying. Furthermore, duodenal nutrients elicit changes in
gastrointestinal motility that may stimulate mechanosensitive vagal afferents.
The degree to which the activity of an individual vagal afferent fiber can be
modified by moth mechanical and nutrient properties in the gut remains unclear.
The present studies evaluated the relationships between distal antral and
proximal duodenal load-sensitive vagal afferent activity and gastroduodenal
motility in response to duodenal nutrient exposure in ketamine-xylazine
anesthetized rats. Duodenal carbohydrate (glucose) and amino acid (peptone)
infusions (0.2 ml/min, 0.2-0.5 kcal/ml) stimulated concentration-dependent
increases in 1) antroduodenal contractions and 2) antral and duodenal vagal
afferent activity beyond those attributable to osmolarity alone. In addition,
duodenal peptone was more effective than equicaloric glucose in eliciting this
vagal activity. These data demonstrate that the proximal duodenum can
discriminate its nutrient chemical contents and that gastroduodenal load
sensitive vagal afferents indirectly transduce nutrient chemical information.
PMID- 9644036
TI - Splanchnic and vagal denervation attenuate central Fos but not AVP responses to
intragastric salt in rats.
AB - We have recently reported that an acute intragastric hypertonic saline load
increases plasma arginine vasopressin (PAVP) and Fos immunoreactivity in several
central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus
(PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral
parabrachial nucleus (LPBN). We hypothesized that these responses are mediated by
stimulation of peripheral osmoreceptors with splanchnic and/or vagal afferent
projections. To test this hypothesis, we examined the effect of bilateral
subdiaphragmatic vagotomy and bilateral splanchnic denervation on the PAVP and
Fos immunoreactivity responses to intragastric hypertonic saline infusion in
awake rats. Compared with responses in sham rats, Fos immunoreactivity responses
were significantly reduced in vagotomized rats in the AP, SON, and PVN, whereas
normal Fos levels were observed in the LPBN. However, vagotomized rats exhibited
a normal increase in PAVP. Splanchnic-denervated rats also exhibited similar
changes in PAVP in response to intragastric hypertonic saline compared with sham
denervated rats, and no differences were observed in Fos immunoreactivity in the
LPBN, SON, and PVN compared with sham rats. However, splanchnic-denervated rats
were observed to have significantly lower Fos staining in the NTS and AP compared
with sham rats. The inability of splanchnic or vagal denervation alone to block
the PAVP response to intragastric hypertonic saline suggests that either
peripheral osmoreceptors project via both splanchnic and vagal afferents to
mediate AVP release or that the observed response of PAVP is due to the
activation of central osmoreceptors in the absence of measurable changes in
plasma osmolality.
PMID- 9644037
TI - Insulin increases fatty acid synthase gene transcription in human adipocytes.
AB - The purpose of this study was to investigate the molecular mechanism whereby
insulin increases expression of a key de novo lipogenic gene, fatty acid synthase
(FAS), in cultured human adipocytes and hepatoma cells. RNA isolated from
cultured adipocytes or from Hep G2 cells treated with or without insulin (20 nM)
was analyzed. In addition, run-on transcription assays and measurements of RNA
half-life were performed to determine the controlled step in FAS gene regulation
by insulin. We demonstrated that FAS mRNA was expressed in both Hep G2 cells and
human adipocytes. Insulin induced an approximately five- and three-fold increase
in FAS mRNA content in adipocytes and hepatoma cells, respectively. Similar
regulation of FAS was observed in adipocytes from lean and obese human subjects.
Furthermore, we demonstrated that the induction of human FAS expression by
insulin was due to increased transcription rate of the FAS gene in human
adipocytes, whereas mRNA stabilization accounted for increased FAS mRNA content
in hepatoma cells. In conclusion, we report here for the first time expression of
human FAS mRNA and its specific transcriptional induction by insulin in cultured
human adipocytes.
PMID- 9644038
TI - Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory
function.
AB - Experiments were carried out to determine the effects of altering the serotonin
(5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized
restrained rats. Local perfusion of the hypothalamus with dialysis solution
containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake
inhibitor), or high potassium significantly increased both colonic temperature
(Tco) and the extracellular concentrations of 5-HT in the hypothalamus.
Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and
Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks
the voltage-dependent sodium channel), zero calcium concentration, or systemic
administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A
agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4
iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and
hyperthermic effects, respectively. The results indicate that elevating the 5-HT
levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in
hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the
hypothalamus reduces the endogenous 5-HT release and results in hypothermic
effects.
PMID- 9644039
TI - Delayed vagal withdrawal slows circulatory but not oxygen uptake responses at
work increase.
AB - The effect of delayed vagal activity withdrawal on cardiorespiratory responses at
an increase in workload was examined. Eleven volunteers (21 +/- 3 yr, 66 +/- 4
kg) performed cycle ergometer exercise at a work rate corresponding to 80% of
ventilatory threshold after 3 min of unloaded cycling. Facial stimulation was
given by applying a vinyl bag filled with cold water (3-5 degrees C) to the face
1 min before to 1 min after the increase in workload (S2 trial) or no stimulation
was given (Nr trial). Oxygen uptake (VO2), heart rate (HR), and cardiac output
(Q) were continuously recorded in four transitions for each trial. Data were
averaged for each subject and trial. Mean response time (MRT, sum of delay and
time constant) was calculated with monoexponential fitting. Facial stimulation
induced acute bradycardia (-10 +/- 5 beats/min in S2 trial). The MRT of HR and Q
was significantly longer in the S2 trials (46 +/- 35 and 37 +/- 23 s) than in the
Nr trials (26 +/- 18 and 28 +/- 19 s, respectively), but no significant change in
VO2 MRT was shown (36 +/- vs. 38 +/- 12 s). These findings suggest that increased
vagal activity delays the central circulatory responses, which does not alter the
VO2 kinetics at the onset of stepwise increase in workload. The maintenance of
VO2 kinetics during acute bradycardia may either reflect the fact that some
intramuscular processes (such as oxidative enzyme inertia) limit VO2 kinetics or
alternatively that increased sympathetic vasoconstriction at some remote site
defends exercising muscle blood flow.
PMID- 9644040
TI - Lateral parabrachial nucleus modulates baroreflex regulation of sympathetic nerve
activity.
AB - Previous studies have demonstrated that the lateral parabrachial nucleus (LPBN)
is an important site for descending modulation of baroreflex control of heart
rate. In the present study it was hypothesized that the LPBN neurons may also
modulate baroreflex control of arterial pressure and sympathetic nerve activity.
In urethan-anesthetized rats, electrical or chemical activation of the LPBN
produced a significant reduction in the magnitude of the baroreflex inhibition of
mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) elicited
by aortic depressor nerve stimulation. Chemical inactivation of the LPBN resulted
in a small increase in baroreflex control of MAP, but baroreflex control of RSNA
was not affected. The results suggest that LPBN neurons have little tonic
influence over baroreflex control of MAP and RSNA in the anesthetized rat. When
the LPBN is activated, however, LPBN neurons may function to reduce the capacity
of the baroreflex to regulate sympathetically mediated increases in arterial
pressure.
PMID- 9644041
TI - Contribution of renal nerves to renal blood flow variability during hemorrhage.
AB - We have examined the role of the renal sympathetic nerves in the renal blood flow
(RBF) response to hemorrhage in seven conscious rabbits. Hemorrhage was produced
by blood withdrawal at 1.35 ml.min(-1).kg-1 for 20 min while RBF and renal
sympathetic nerve activity (RSNA) were simultaneously measured. Hemorrhage was
associated with a gradual increase in RSNA and decrease in RBF from the 4th min.
In seven denervated animals, the resting RBF before hemorrhage was significantly
greater (48 +/- 1 vs. 31 +/- 1 ml/min intact), and the decrease in RBF did not
occur until arterial pressure also began to fall (8th min); however, the overall
percentage change in RBF by 20 min of blood withdrawal was similar. Spectral
analysis was used to identify the nature of oscillations in each variable. Before
hemorrhage, a rhythm at approximately 0.3 Hz was observed in RSNA, although not
in RBF, whose spectrogram was composed mostly of lower-frequency (< 0.25 Hz)
components. The denervated group of rabbits had similar frequency spectrums for
RBF before hemorrhage. RSNA played a role in dampening the effect of oscillations
in arterial pressure on RBF as the transfer gain between mean arterial pressure
(MAP) and RBF for frequencies > 0.25 Hz was significantly less in intact than
denervated rabbits (0.83 +/- 0.12 vs. 1.19 +/- 0.10 ml.min(-1).mmHg-1).
Furthermore, the coherence between MAP and RBF was also significantly higher in
denervated rabbits, suggesting tighter coupling between the two variables in the
absence of RSNA. Before the onset of significant decreases in arterial pressure
(up to 10 min), there was an increase in the strength of oscillations centered
around 0.3 Hz in RSNA. These wer accompanied by increases in the spectral power
of RBF at the same frequency. Arterial pressure fell in both groups of animals,
the dominant rhythm to emerge in RBF was centered between 0.15 and 0.20 Hz and
was present in intact and denervated rabbits. It is speculated that this myogenic
in origin. We conclude that RSNA can induce oscillations in RBF at 0.3 Hz, plays
a significant role in altering the effect of oscillations in arterial pressure on
RBF, and mediates a proportion of renal vasoconstriction during hemorrhage in
conscious rabbits.
PMID- 9644042
TI - Acclimation to humid heat lowers resting core temperature.
AB - The purpose of this study was to test the hypothesis that a reduction in resting
rectal temperature (Tre) is partially responsible for the attenuation in the rise
of core temperature during the heat exposure following acclimation to humid heat.
Nine male volunteers completed 7 days of acclimation, performing 2 h of exercise
per day in a hot, humid environment (35 degrees C, 75% relative humidity). Mean
(+/- SD) ending Tre significantly (P < 0.05) decreased from 38.9 +/- 0.5 degrees
C on day 1 to 38.3 +/- 0.4 degrees C on day 7. Likewise, mean (+/- SD) resting
Tre significantly (P < 0.05) decreased from 37 +/- 0.3 to 36.7 +/- 0.4 degrees C.
In fact, all nine men showed a decrease in resting Tre from day 1 to day 7,
ranging from -0.1 to -0.5 degrees C. In addition, resting Tre and ending Tre were
significantly correlated (r = 0.68). However, the mean increases in Tre (ending
Tre minus resting Tre) and heat storage that occurred on each of the 7
acclimation days were not significantly different. These results support the
hypothesis that a reduction in resting Tre is partially responsible for the
attenuation in ending Tre during heat exposure following short-term acclimation
to humid heat.
PMID- 9644043
TI - Increased oxidative capacity does not protect skeletal muscle fibers from
eccentric contraction-induced injury.
AB - Isometric electrical stimulation was delivered to rabbit dorsiflexor muscles at
10 Hz for 1 s on and 1 s off over 30 min, 5 days/wk for 3 wk to induce an
increase in muscle oxidative capacity. Stimulation-trained muscles as well as
untrained muscles were then subjected to a 30-min eccentric exercise bout to test
whether increased oxidative capacity provided a protective effect against muscle
injury. Electrical stimulation results in significant training of both the
extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, with EDL
citrate synthase (CS) activity increasing an average of 67% (P < 0.0001) and TA
CS activity increasing by 27% (P < 0.05). For all parameters measured, the
magnitude of change was much greater for EDL than for TA muscle. Dorsiflexor
fatigability decreased significantly during the 3-wk training period (P <
0.0001), whereas the EDL TA individually showed strong decreasing trends in
fatigability after training. TA and EDL capillary density measured
histomorphometrically increased from 839 +/- 56 to 1,026 +/- 71 mm-2 (P = 0.07)
and from 589 +/- 37 to 792 +/- 66 mm-2 (P < 0.05), respectively. TA and EDL
capillary-to-fiber ratio increased from 1.32 +/- 0.10 to 1.55 +/- 0.16 (P > 0.2)
and 1.08 +/- 0.07 to 1.36 +/- 0.14 (P > 0.1), respectively. Type 2A fiber type
percentage increased after stimulation training by 68% (P < 0.0001) for the EDL
and by 32% (P > 0.1) for the TA at the expense of type 2D fibers. Despite the
large training effect for the EDL and the modest training effect for the TA, no
differences were observed between stimulation-trained and untrained groups for
maximum dorsiflexion torque (P > 0.3) or maximum tetanic tension (P > 0.3) after
eccentric contraction-induced injury. Additionally, no significant correlation
was observed between CS activity and maximum tetanic tension after eccentric
contraction-induced injury for either muscle (P > 0.2). Thus we conclude that
increasing muscle oxidative capacity by isometric electrical stimulation training
did not protect muscle against eccentric contraction-induced injury.
PMID- 9644044
TI - Persistence of metabolic rhythmicity during fasting and its entrainment by
restricted feeding schedules in rats.
AB - The presence of a food-entrainable oscillator (FEO) independent from the SCN is
now well established, but until now its location and characterization have been
elusive. Because its expression requires priming of the animal's metabolism
toward a catabolic state, it is possible that metabolic rhythms may be related to
FEO. The present study was designed to determine whether metabolic rhythms
persist during fasting and whether such rhythms could be entrained to a
restricted feeding schedule. The results indicate persistent rhythms of
triacylglycerides, free fatty acids, glucose, and proteins during fasting,
whereas ketone bodies and liver glycogen changed their concentration as a
function of fasting. Daily food pulses of 2 h entrained the rhythms of
triacylglycerides and free fatty acids and restored ketone bodies and liver
glycogen to similar levels as controls. Neither glucose nor proteins were
affected by the food pulse. These results indicate the relevance of lipid
metabolism as a phenomenon associated with the FEO.
PMID- 9644045
TI - Effects of daily sodium intake and ANG II on cortical and medullary renal blood
flow in conscious rats.
AB - Implanted optical fibers and laser-Doppler flow measurement techniques were used
for the sequential measurement of regional renal blood flow in conscious rats to
determine the effects of an increase of daily NaCl intake on the renal cortical
blood flow and blood flow to the outer and inner medulla. Cortical blood flow was
increased significantly (32%) by the second day when NaCl intake was increased
from 1 to 7 meq/day and was increased further (50%) on the second day after a
further elevation of NaCl intake to 13 meq/day. Blood flow to the outer and inner
medulla was not changed as NaCl intake was elevated. The increase in renal
cortical flow was closely associated with significant reductions in circulating
concentrations of ANG II from 31 to 16 pg/ml. Rats given a continuous infusion of
nonpressor does of ANG II (5.0 ng.kg(-1).min-1) to maintain constant plasma
concentrations of ANG II as sodium intake was increased exhibited no increase of
cortical flow. We conclude that reductions of plasma ANG II associated with
incremental increases of daily sodium intake result in a rise of renal cortical
flow. The elevated blood flow to the renal cortex may enhance sodium excretion
and contribute to long-term sodium homeostasis.
PMID- 9644046
TI - Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the
diabetic db/db mouse.
AB - Genetically diabetic db/db mice show greater neural and behavioral responses to
sugars than lean control mice. The present study examined chorda tympani
responses of db/db mice to nonsugar sweeteners and their inhibition by a sweet
response inhibitor, gurmarin. The results showed that responses to sucrose,
saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine, were
approximately 1.5 times greater in db/db mice than in control mice. Treatment of
the tongue with gurmarin suppressed responses to these sweeteners in db/db and
control mice, but the extent of suppression was considerably smaller in db/db
mice. The magnitudes of gurmarin-sensitive components of the response to
sweeteners in db/db mice were not significantly different from those in control
mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice
were about twice as large as those in control mice. These results suggest that
the enhancement of chorda tympani responses in db/db mice to sucrose and other
nonsugar sweeteners may occur through gurmarin-insensitive membrane components.
PMID- 9644047
TI - Leptin depolarizes rat hypothalamic paraventricular nucleus neurons.
AB - Leptin, the protein product of the ob/ob gene, is thought to have a central site
of action, presumably within the hypothalamus, through which it regulates feeding
behavior. THe paraventricular nucleus (PVN) is one structure that has been
implicated in regulating feeding behavior. Using patch-clamp recording
techniques, this study examines the direct membrane effects of leptin on neurons
in a coronal PVN slice. Bath application of the physiologically active leptin
fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the
type I cells tested (n = 17) and 67% of the type II cells tested (n = 9). By
contrast, the physiologically inactive leptin fragment (amino acids 57-92) had no
discernible effect on membrane potential (n = 7). The effects of this peptide
were unaffected following synaptic isolation of the cells by bath application of
the sodium channel blocker tetrodotoxin (n = 5). Voltage clamp recordings in six
cells demonstrated that leptin increased a nonspecific cation conductance with a
reversal potential near -30 mV. These findings suggest that neurons in PVN may
play an important role in the central neuronal circuitry involved in the
physiological response to leptin.
PMID- 9644048
TI - Bioartificial Organs: Science and Technology. Conference proceedings. Nashville,
Tennessee, USA. July 21-26, 1996.
PMID- 9644049
TI - Cancer: Genetics and the Environment. Proceedings of a conference. New York, New
York, USA. November 15-16, 1996.
PMID- 9644050
TI - Suicide Research Workshop: From the Bench to the Clinic. Proceedings. Washington
DC, USA. November 14-15, 1996.
PMID- 9644051
TI - Synthesis and dopamine receptor selectivity of the benzyltetrahydroisoquinoline,
(R)-(+)-nor-roefractine.
AB - (R)-(+)-nor-Roefractine (1) was synthesized by the Bischler-Napieralski route,
using asymmetric reduction of the 1, 2-didehydro precursor imine with sodium (S)
N-CBZ-prolinyloxyborohydride. Compound 1 was able to displace [3H]-raclopride (a
D2 dopamine receptor-selective ligand) from its specific binding sites in rat
striatum with selectivity vs [3H]-SCH23390 (D1 dopamine receptor-selective
ligand).
PMID- 9644052
TI - Isolation and structural studies on the chemical constituents of skimmialaureola
AB - Studies on the chemical constituents of the aerial parts of Skimmia laureola have
led to the isolation of four new alkaloids, ptelefoliarine (1),
acetoxyptelefoliarine (2), acetoxyedulinine (3), and orixiarine (4). Their
structures were established by spectroscopic studies.
PMID- 9644053
TI - Novel quinone methides from Salacia kraussii with in vitro antimalarial activity.
AB - Three novel quinone methides, i.e., 28-nor-isoiguesterin-17-carbaldehyde (1), 17
(methoxycarbonyl)-28-nor-isoiguesterin (2), and 28-hydroxyisoiguesterin (3),
together with the known celastrol (5), pristimerin (6), and isoiguesterol (7),
were isolated from the roots of Salacia kraussii (Celastraceae) by bioassay
guided fractionation. The structures of the compounds were determined by DEPT and
2D NMR techniques. The isolates showed antimalarial activity 30-50-fold greater
than their cytotoxicity (in HT-29 cells) in vitro, and they showed an additive
effect when combined with each other. In vivo, 2 was found to be inactive against
blood stages of Plasmodium berghei in mice after oral and parenteral
administration, and the compound was toxic with increasing concentrations.
PMID- 9644054
TI - Theonellapeptolide IIIe, a new cyclic peptolide from the New Zealand deep water
sponge, Lamellomorpha strongylata.
AB - The structure, stereochemistry, and conformation of theonellapeptolide IIIe (1),
a new 36-membered ring cyclic peptolide from the New Zealand deep-water sponge
Lamellomorpha strongylata, is described. The sequence of the cytotoxic peptolide
was determined through a combination of NMR and MS-MS techniques and confirmed by
X-ray crystal structure analysis, which, with chiral HPLC, established the
absolute stereochemistry.
PMID- 9644055
TI - Enhancement of NO production in activated macrophages in vivo by an antimalarial
crude drug, Dichroa febrifuga.
AB - The effect of an antimalarial crude drug, Dichroafebrifuga Lour. on nitric oxide
(NO) production in bacillus Calmette Guerin-induced mouse peritoneal macrophages
activated by lipopolysaccharide was investigated. The NO production was
significantly enhanced by an oral administration of a MeOH extract of D.
febrifuga. Febrifugine (1) was isolated as the main active compound, and the
activation was dose-dependent in the dosage range of 0.1-1 mg/kg/day.
PMID- 9644056
TI - Gmelinosides A-L, twelve acylated iridoid glycosides from Gmelina arborea.
AB - Besides the known iridoids 6-O-alpha-L-rhamnopyranosylcatalpol (1), 6-O-(3"-O
trans-feruloyl)-alpha-L-rhamnopyranosylcatalpol (14), 6-O-(2"-O-acetyl-3", 4"-O
di-trans-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (15) and the known
phenylpropanoid glycosides verbascoside (acteoside) and martynoside, 12 new
acylated iridoid glycosides named gmelinosides A-L (2-13) have been isolated from
the leaves of Gmelina arborea. These compounds were structurally characterized
using a variety of spectral methods.
PMID- 9644057
TI - Certain norditerpenoid alkaloids and their cardiovascular action.
AB - Thirteen new derivatives of norditerpenoid alkaloids, namely, 8-deacetyl-8-p
aminobenzoyldelphinine (1), 8-deacetyl-8-anthranoyldelphinine (2), 8-deacetyl-8
(4-hydroxy-3-methoxycinnamoyl)delphinine (3), 16-demethoxy-15,16-didehydro-8-p
anisoyl-14-benzoyldelpho nine (4), 6-acetylheteratisine N-oxide (6), 3,8
diacetylfalconerine (7), 8-stearoylfalconerine (8), 8-linolenylfalconerine (9),
13-acetylpyrodelphinine (11), 13-acetyldelphinine N-oxide (13), N-deacetyl-8,9
diacetyllappaconitine (14), 8, 9-(methylenedioxy)lappaconine (15), and 16
epipyroaconitine N-oxide (17), were prepared, and their structures were
established by analysis of spectroscopic data (1D and 2D NMR, HRFABMS). The
preliminary in vivo cardiovascular action (hypotensive, bradycardic, and
ventricular arrhythmias) of these new compounds was tested in male Sprague-Dawley
rats. The results are reported herein.
PMID- 9644058
TI - Macrocyclic diterpenoids from Euphorbia semiperfoliata.
AB - In addition to known compounds, the aerial parts of E. semiperfoliata afforded an
abietanolide (3), 13 jatrophane polyesters (4-9, 12, 14-19), two 4-deoxyphorbol
diesters (23, 24), and a pair of epimeric diterpenes (21, 22) with a novel carbon
skeleton, which was named euphoperfoliane. Structures were determined by
spectroscopic analysis, and the main conformational features of jatropha-6(17),11
dienes are discussed in detail. The obtained isolation yield of several
jatrophanes was unprecedented within the spurges (Euphorbia spp.), making E.
semiperfoliata a unique source of macrocyclic diterpenoids.
PMID- 9644059
TI - Complement-inhibiting cucurbitacin glycosides from Picria fel-terrae.
AB - Four cucurbitacin glycosides were isolated from Picriafel-terrae and identified
by MS and NMR spectroscopy as picfeltarraenin IA (1), picfeltarraenin IB (2),
picfeltarraenin IV (4), and a new compound picfeltarraenin VI (3)
(picfeltarraegenin I 3-O-beta-D-xylopyranoside). All four compounds acted as
inhibitors on both the classical and alternative pathways of the complement
system, with compound 3 exhibiting the highest inhibitory activity (IC50 29 +/- 2
microM and 21 +/- 1 microM, respectively). Compounds 1-4 showed no antiviral,
antibacterial, or antifungal activities. Picfeltarraenin IA and IB were tested in
an in vitro human tumor cell line panel, but displayed no cytotoxic activity.
PMID- 9644060
TI - Vanicosides C-F, new phenylpropanoid glycosides from Polygonum pensylvanicum.
AB - The isolation of the protein kinase C inhibitors, vanicoside A (1) and vanicoside
B (2), from Polygonum pensylvanicum prompted continued interest in the active
principles of this plant. A new, more efficient isolation procedure has been
developed to facilitate separation of homologues of vanicosides A and B from the
complex extract. Several new phenylpropanoid glycosides have since been isolated.
The structures of these principles were determined to be 2'-O
acetylhydropiperoside (4), 6'-O-p-coumarylhydropiperoside (5), 4'-O
acetylvanicoside A (6), and 3'-O-acetylvanicoside B (7) using negative ion FABMS,
1H NMR, and 2D NMR techniques.
PMID- 9644061
TI - Cytotoxic isoflavans from Eysenhardtia polystachya.
AB - Two new cytotoxic isoflavans, (3S)-7-hydroxy-2',3',4',5', 8-pentamethoxyisoflavan
(1) and (3S)-3',7-dihydroxy-2',4',5', 8-tetramethoxyisoflavan (2), were isolated
from the bark and trunks of Eysenhardtia polystachya (Leguminosae), together with
the known constituents stigmasterol, isoduartin, cuneatin, 7-hydroxy-2',4', 5'
trimethoxyisoflavone, and 3,4-dimethoxy-8, 9-(methylenedioxy)pterocarpan. The
structures of 1 and 2 were elucidated on the basis of spectroscopic methods. The
antimicrobial, cytotoxic, and insecticidal potential of some of these compounds
were evaluated. The isoflavans 1, 2, and isoduartin (2', 7-dihydroxy-3',4',8
trimethoxyisoflavan) displayed moderate cytotoxic activity against KB cell lines.
PMID- 9644062
TI - Lignans from Chilean propolis.
AB - Three new (1, 3, 4) and two known lignans (2 and 5) were isolated from Chilean
propolis. Compound 1 was identified as a trimeric coniferyl alcohol acetate and 3
as the diastereomer of the dimeric coniferyl alcohol acetate 2. Compound 4 was
identified as a dihydrobenzofuran lignan aldehyde, which was isolated together
with the related known acetate 5.
PMID- 9644063
TI - Cytotoxic quassinoids from Simaba cedron.
AB - Four new quassinoids, cedronolactones A-D (1-4), together with nine known
compounds, simalikalactone D (5), chaparrinone (6), chaparrin (7), glaucarubolone
(8), glaucarubol (9), samaderine Z (10), guanepolide (11), ailanquassin A (12),
and polyandrol (13), were isolated from the wood of Simaba cedron. The chemical
structures of 1-4 were elucidated on the basis of their chemical and spectral
properties. Cedronolactone A (1) was shown to exhibit a significant in vitro
cytotoxicity (IC50 0.0074 microg/mL) against P-388 cells.
PMID- 9644064
TI - Cytotoxic and insecticidal constituents of the unripe fruit of Persea americana.
AB - Unripe avocado fruit (Persea americana) was subjected to a bioactivity-directed
fractionation, as monitored via the brine shrimp lethality assay, to isolate
three major bioactive constituents (1-3). Compounds 1-3 all have a 1,2,4-triol
moiety and a long aliphatic chain that terminates as either an alkane, alkene, or
alkyne, respectively; 1 is new, while 2 and 3 have been described previously but
not as cytotoxic or pesticidal agents. All have activity against six human tumor
cell lines in culture and show selectivity for human prostate adenocarcinoma (PC
3) cells with 3 being nearly as potent as adriamycin. Also, when tested against
yellow fever mosquito larva, 3 was more effective than rotenone, a natural
botanical insecticide and positive control.
PMID- 9644065
TI - Hovetrichosides C-G, five new glycosides of two auronols, two neolignans, and a
phenylpropanoid from the bark of Hovenia trichocarea.
AB - Two 2-hydroxy-2-benzylcoumaranone glycosides, 2,4, 6-trihydroxy-2-[(4'
hydroxyphenyl) methyl]-3(2H)-benzofuranone-4-yl-beta-D-glucopyranoside (maesopsin
4-O-glucoside) (1) and 2,4,6-trihydroxy-2-[(4'-hydroxyphenyl) methyl]-3(2H)
benzofuranone-4-yl-beta-D-glucopyranosido-4'-y l-alpha-L -rhamnopyranoside
(maesopsin 4-O-glucosido 4'-O-rhamnoside) (2), two neolignan glycosides, 2R-(E)
2, 3-dihydro-2-(4'-hydroxy-3'-methoxylphenyl)-5-(3"-hydroxy-1"-pro pen yl) -7
methoxy-3-benzofuranmethanol-4'-yl-beta-D-glucopyranosyl-(1-->3 )-[ beta-D
glucopyranosyl-(l-->2)]-beta-d-glucopyranoside (3) and (threo) 1-(4'-hydroxy-3'
methoxy)-2-(4"-hydroxymethyl-2", 6"-dimethoxyphenoxy)-propane-1,3-diol-4'-yl-beta
d-glucopynosid e (4), and a phenylpropanoid glycoside, 3-methoxy-5-(2'-propenyl)
1, 2-benzenediol-1-yl-beta-D-apiofuranosyl-(1-->6)-beta-D- glucopyransodie (5)
were isolated from the bark of Hovenia trichocarea. Compounds 1-5 were named
hovetricosides C-G, respectively, and their structures were established by
extensive NMR experiments and chemical methods. Also obtained in this
investigation were the known compounds acanthoside B, kelampayoside A,
shashenoside I, and 3,4, 5-trimethoxyphenol-1-O-beta-D-xylopyranosyl-(1-->6)-beta
D- glucopyranoside.
PMID- 9644066
TI - Epolones: novel sesquiterpene-tropolones from fungus OS-F69284 that induce
erythropoietin in human cells.
AB - In the course of our screening for small molecule modulators of erythropoietin
gene expression, two novel sesquiterpene tropolones and pycnidone were isolated
from a culture of OS-F69284 (ATCC 74390). Their structures were elucidated by
extensive 1H and 13C NMR spectroscopic studies and chemical reactions. These
compounds induced erythropoietin gene expression 5-fold at a concentration of 1
1.6 microM.
PMID- 9644067
TI - 5-Methoxyjusticidin A, a new arylnaphthalene lignan from Protium unifoliolatum.
AB - A new arylnaphthalene lignan, 9-(1,3-benzodioxol-5-yl)-4,5,6, 7
tetramethoxynaphtho[2,3-C]furan-1(3H)-one (5-methoxyjusticidin A, 1), was
isolated from a Et2O extract of the wood of Protium unifoliolatum. The structure
of 1 was determined by both spectroscopic and X-ray crystallographic methods.
PMID- 9644068
TI - New sesquiterpenoids from the jordanian medicinal plant inula viscosa
AB - Four new and 14 known compounds have been isolated from Inula viscosa of
Jordanian origin. The new isolates are 11(13)-eudesmen-12-oic acids, 3beta
hydroxyilicic acid (1), 3alpha-hydroxy-epi-ilicic acid (2), 2alpha-hydroxyilicic
acid (3) and 9beta-hydroxy-2-oxoisocostic acid (4).
PMID- 9644069
TI - A new benzoylglucoside and a new prenylated isoflavone from lophira lanceolata
AB - A new benzoylglucoside, lanceoloside A (1), and a new prenylated isoflavone,
lanceolone (2), have been isolated from the air-dried leaves of Lophira
lanceolata. Both structures were established from spectroscopic and chemical
evidence.
PMID- 9644070
TI - Mollenines A and B: new dioxomorpholines from the ascostromata of Eupenicillium
molle.
AB - Two new dioxomorpholines (1 and 2) have been isolated from the sclerotioid
ascostromata of Eupenicillium molle (NRRL 13062). Their structures were
determined by analysis of NMR data. Mollenine A (1) exhibited moderate
cytotoxicity and antibacterial activity, but neither compound displayed
significant antiinsectan activity.
PMID- 9644071
TI - Magnone A and B, novel anti-PAF tetrahydrofuran lignans from the flower buds of
Magnolia fargesii.
AB - In a search for platelet-activating-factor (PAF) antagonists, two new lignan
compounds were isolated from the Chinese crude drug shin-i, the flower buds of
Magnolia fargesii. Their structures were elucidated as (2S,3R,4R)-tetrahydro-2
(3,4-dimethoxyphenyl)-4-(3, 4-dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone
A, 1) and (2S,3R, 4R)-tetrahydro-2-(3,4,5-trimethoxyphenyl)-4-(3, 4
dimethoxybenzoyl)-3-(hydroxymethyl)furan (magnone B, 2). Magnones A and B showed
antagonistic activity against PAF in the [3H]PAF receptor binding assay with the
IC50 values of 3.8 x 10(-5) M and 2.7 x 10(-5) M, respectively.
PMID- 9644072
TI - Two new ergostane-type steroidal lactones from Withania coagulans.
AB - Two new withanolides (steroidal lactones) named coagulin F [27-hydroxy-14,20
epoxy-1-oxo-(22R)-witha-3,5,24-trienolide] (1) and coagulin G [17beta,27
dihydroxy-14,20-epoxy-1-oxo-(22R)-witha-2,5, 24-trienolide] (2) were isolated
from the whole plant of Withania coagulans, and their structures were deduced by
spectral analysis.
PMID- 9644073
TI - Two 6-substituted 5,6-dihydropyran-2-ones from piper reticulatum
AB - The Me2CO extract of the aerial parts of Piper reticulatum yielded two 6
substituted 5,6-dihydropyran-2-ones 1 and 2 and dihydrowisanidine. The structures
of 1 and 2 were elucidated by spectroscopic methods.
PMID- 9644074
TI - Binaphthalenone glycosides from African chewing sticks, Diospyros lycioides.
AB - Our laboratory has engaged in the exploration of active antimicrobial principles
present in chewing sticks commonly used by the African and Middle Eastern
countries as a mechanical oral hygiene aid in place of tooth brushing. During
this investigation, a methanol extract from the twigs of Diospyros lycioides, a
Namibia tooth cleaning stick, demonstrated antimicrobial activity against common
oral pathogens including Streptococcus mutans and Porphyromonas gingivalis (MICs
2.5 and 0.156 mg/mL). Subsequent fractionation and purification of this extract
led to the identification of two novel binaphathalenone glycosides: 1', 2
binaphthalen-4-one-2',3-dimethyl-1,8'-epoxy-1,4',5,5',8, 8'-hexahydroxy-8-O-beta
glucopyranosyl-5'-O-beta-xylopyranosyl(1-- >6) -beta-glucopyranoside (1) and 1',2
binaphthalen-4-one-2', 3-dimethyl-1,8'-epoxy-1,4',5,5',8,8'-hexahydroxy-5', 8-di
O-beta-xylopyranosyl(1-->6)-beta-glucopyranoside (2). Their structures were
established using spectroscopic techniques. Examination of the antimicrobial
activity of these two compounds revealed positive but only marginal growth
inhibition against the test cariogenic pathogens, S. sanguis and Streptococcus
mutans.
PMID- 9644075
TI - Synthesis of 4-acetylbenzoxazolin-2(3H)-one reported from zea mays
AB - A three-step alternative synthesis of 4-acetylbenzoxazolin-2(3H)-one (4) is
reported. Starting from inexpensive 3-hydroxyacetophenone (1) 3-hydroxy-2
nitroacetophenone (2) is prepared by nitration followed by catalytic
hydrogenation to yield 2-amino-3-hydroxyacetophenone (3) in which a C=O unit is
inserted by means of bis(trichloromethyl)carbonate (triphosgene) in the presence
of triethylamine to afford 4 in 35% overall yield.
PMID- 9644076
TI - New ceramide from marine sponge Haliclona koremella and related compounds as
antifouling substances against macroalgae.
AB - A new ceramide N-docosanoyl-d-erythro-(2S, 3R)-16-methyl-heptadecasphing-4(E)
enine (C22 ceramide) was isolated from the marine sponge Haliclona koremella as
an antifouling substance against macroalgae. The structure of this substance was
elucidated by spectral means. Antifouling activity of several related compounds
was also examined.
PMID- 9644077
TI - Sesquiterpenes from the leaves of Tithonia diversifolia.
AB - Two new compounds, a germacrane sesquiterpene, 1-acetyltagitinin A (1), and a
guaianane sesquiterpene, 8beta-isobutyryloxycumambranolide (2), were isolated
from leaves of Tithonia diversifolia, together with two known compounds, methyl
3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oa te and tagitinin A. The
structures of compounds 1 and 2 were elucidated on the basis of spectral and
chemical evidence.
PMID- 9644078
TI - New diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.
AB - An abietane diterpene, 11,14-dihydroxy-8,11,13-abietatrien-7-one (1); a seco
abietane diterpene, obtuanhydride (2); and an isopimarane diterpene, 18,19-O
isopropylidene-18, 19-dihydroxyisopimara-8(14),15-diene (3) were isolated from
the heartwood of Chamaecyparis obtusa var. formosana. The structures of these new
compounds were elucidated by spectroscopic methods.
PMID- 9644079
TI - Studies on the secondary metabolites from the Indian gorgonian Subergorgia
suberosa: isolation and characterization of four analogues of the cardiotoxin
subergorgic acid.
AB - Chemical investigation of the methanol extract of the Indian ocean gorgonian
coral Subergorgia suberosa resulted in isolation and identification of four novel
compounds 2-5. Structural investigation revealed compound 1 to be subergorgic
acid and the others its analogues.
PMID- 9644080
TI - Isolation of a novel diterpene triacetate from two soft corals of the order
alcyonacea
AB - Alcyonolide 5 (5), a novel diterpene triacetate, has been isolated from two soft
corals of the order Alcyonacea.
PMID- 9644081
TI - A new taxane diterpenoid from Taxus mairei.
AB - A new 11(15-->1)-abeotaxane diterpene, taxumairol K (1), has been isolated from
the ethanolic extract of the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y.
Hu. The structure of 1 was determined as 9alpha-(benzoyloxy)-2alpha,4alpha-
diacetoxy-5beta ,20-epoxy-1beta, 7beta,10beta,13alpha-tetrahydroxy-11(15-->1)
abeota xane on the basis of spectral analysis. Taxumairol K (1) exhibited mild
cytotoxicity against HeLa tumor cells.
PMID- 9644082
TI - Biosynthesis of phytol in the cyanobacterium synechocystis sp. UTEX 2470:
utilization of the non-mevalonate pathway
AB - The biosynthesis of phytol in the cyanobacterium Synechocystis sp. UTEX 2470 has
been examined using 6,6-2H2-d-glucose, 2-13C-d-glucose, and U-13C6-d-glucose as
precursors. Analysis of the isolated phytol using deuterium or 13C NMR showed
labeling patterns consistent with incorporation of labeled glucose via the non
mevalonate pathway to terpenes.
PMID- 9644083
TI - Novel cytotoxic cembranoids from the soft coral Sinularia flexibilis.
AB - Three new cytotoxic cembranoid diterpenes, sinuflexolide (1),
dihydrosinuflexolide (2), and sinuflexibilin (3), have been isolated from the
soft coral Sinularia flexibilis. The structures of compounds 1-3 were determined
by spectral and X-ray crystallographic analysis.
PMID- 9644084
TI - New pyrrole alkaloids from Solanum sodomaeum.
AB - Two new pyrrole alkaloids, solsodomine A and B, were isolated from the fresh
berries of Solanum sodomaeum L., collected from the Libyan desert. The structures
of these compounds were established by 2D-NMR, including 15N NMR spectroscopy and
chemical degradation. Solsodomine A (1) shows activity against Mycobacterium
intracellulare. This is the first report of pyrrole alkaloids from the genus
Solanum.
PMID- 9644085
TI - Two (Z)-dehydrobutyrine-containing microcystins from a hepatotoxic bloom of
Oscillatoria agardhii from Soulseat Loch, Scotland.
AB - Two (Z)-dehydrobutyrine(Dhb)-containing microcystins, [d-Asp3, (Z)
Dhb7]microcystin-HtyR (1) and [d-Asp3, (Z)-Dhb7]microcystin-LR (2), were isolated
from a hepatotoxic bloom of the cyanobacterium Oscillatoria agardhii from a
freshwater lake in Scotland. The geometrical structure of the Dhb units in the
microcystins was determined as Z on the basis of NOE and ROESY experiments.
PMID- 9644086
TI - Dehydroradiosumin, a trypsin inhibitor from the cyanobacterium Anabaena
cylindrica.
AB - Dehydroradiosumin, a novel potent trypsin inhibitory dipeptide, was isolated from
the freshwater cyanobacterium Anabaena cylindrica (NIES-19). Its structure was
elucidated as 1 on the basis of 2D NMR data and chemical degradation. The IC50 of
1 against trypsin was 0.1 microg/mL.
PMID- 9644087
TI - Isolation of 2-(3'-bromo-4'-hydroxyphenol)ethanamine from the New Zealand
ascidian Cnemidocarpa bicornuta.
AB - From the ascidian Cnemidocarpa bicornuta, 2-(3'-bromo-4'-hydroxyphenol)ethanamine
(3'-bromotyramine) (1) has been isolated along with the previously reported
sponge metabolite, 1,3-dimethylisoguanine. The structure of 1 was confirmed by
synthesis.
PMID- 9644088
TI - Dihydrotubastrines: phenethylguanidine analogues from the Indo-Pacific marine
sponge Petrosia cf. contignata.
AB - Two phenethylguanidine derivatives, 7,8-dihydrotubastrine (1) and 4-deoxy-7,8
dihydrotubastrine (2), along with the sterol xestobergsterol A (3), were isolated
from the marine sponge Petrosia cf. contignata. The structures of the new natural
products 1 and 2 were based on spectroscopic data and comparison to the
literature properties for semisynthetic 1. This is the first example from this
compound class with a saturated acyclic C2 unit.
PMID- 9644091
TI - From the Editors.
PMID- 9644092
TI - Zinc, iron, and magnesium status in athletes--influence on the regulation of
exercise-induced stress and immune function.
AB - Intense physical exercise has been shown to be associated with immunosuppression
and increased rate of infection. The immunosuppressive effect of exhaustive
exercise has been attributed to a reduced helper/suppressor T-cell ratio, low
salivary levels of immunoglobulin-A, decreased lymphocyte proliferative response
and natural killer cell activity, and elevation of stress hormones. Yet some
athletes can withstand intense training periods without health problems while
others are prone to infections. Thus it has been postulated that other factors
may interfere with immunoregulation. The notion that macro- and micronutrients
are involved in the regulation of immunological processes and the ability to cope
with muscular and systemic exercise stress has been gaining attention.
Particularly trace elements have been shown to be related to cell mediated and
humoral immunity such as NK-cell activity, T- and B-cell functions, and cytokine
release. Many investigations have reported decreased concentrations of trace
elements in blood and tissues after training and competition. However, the
magnitude of losses is highly dependent on the type and intensity of exercise,
the individual regulatory state, and most important, nutrition. This paper
reviews the data on zinc, iron, and magnesium status in athletes and summarizes
the consequences of deficiencies in these trace elements regarding exercise
tolerance and immune function. These elements were chosen since there is evidence
they are related to exercise-induced stress and immune function.
PMID- 9644093
TI - Immunological hazards from nutritional imbalance in athletes.
AB - This review examines the influences of nutritional imbalance on immune function
of competitive athletes, who may adopt an unusual diet in an attempt to enhance
performance. A major increase in body fat can have adverse effects on immune
response. In contrast, a negative energy balance and reduction of body mass are
likely to impair immune function in an already thin athlete. A moderate increase
in polyunsaturated fat enhances immune function, but excessive consumption can be
detrimental. Since endurance exercise leads to protein catabolism, an athlete may
need 2.0 g/kg protein rather than the 0.7-1.0 g/kg recommended for a sedentary
individual. Both sustained exercise and overtraining reduce plasma glutamine
levels, which may contribute to suppressed immune function postexercise. A large
intake of carbohydrate counters glutamine depletion but may also modify immune
responses by altering the secretion of glucose-regulating hormones. Vitamins are
important to immune function because of their antioxidant role. However, the
clinical benefits of vitamin C supplementation are not enhanced by the use of
more complex vitamin mixtures, and excessive vitamin E can have negative effects.
Iron, selenium, zinc, calcium, and magnesium ion all influence immune function.
Supplements may be required after heavy sweating, but an excessive intake of iron
facilitates bacterial growth. In making dietary recommendations to athletes, it
is important to recognize that immune response can be jeopardized not only by
deficiencies but also by excessive intake of certain nutrients. The goal should
be a well-balanced diet.
PMID- 9644094
TI - Glutamine, exercise, and the immune system--is there a link?
AB - Glutamine is known to be important for cells replicating in culture. It has been
proposed that the decrease in plasma glutamine concentration in relation to
catabolic conditions, including strenuous exercise, resulting in a lack of
glutamine for cells of the immune system, is responsible for the transient
postexercise immunosuppression. This review discusses the potential role of
glutamine on the postexercise in-vitro changes in immune parameters. Furthermore,
the value of glutamine as a nutritional supplement to athletes and the possible
influence on these parameters is reviewed.
PMID- 9644095
TI - Influence of carbohydrate on the immune response to intensive, prolonged
exercise.
AB - Many components of the immune system exhibit change after prolonged, heavy
exertion, indicating that the immune system is suppressed and stressed, albeit
transiently, following prolonged endurance exercise. Whether these immune changes
compromise host protection against viruses is still undetermined. Various
attempts have been made to alter the changes in immunity following heavy exertion
through nutritional or chemical means, with the most impressive results reported
thus far in the carbohydrate supplementation studies. Earlier research had
established that a reduction in blood glucose levels is linked to hypothalamic
pituitary-adrenal activation, an increased release of adrenocorticotrophic
hormone and cortisol, increased plasma growth hormone, decreased insulin, and a
variable effect on blood epinephrine levels. Data from two studies of 30 marathon
runners and 10 triathletes suggest that carbohydrate compared to placebo
ingestion is associated with higher plasma glucose levels, an attenuated cortisol
and growth hormone response, fewer perturbations in blood immune cell counts,
lower granulocyte and monocyte phagocytosis and oxidative burst activity, and a
diminished pro- and anti-inflammatory cytokine response. Overall, the hormonal
and immune responses to carbohydrate compared to placebo ingestion suggest that
physiologic stress is diminished, although clinical significance awaits further
research.
PMID- 9644096
TI - Importance of TNF-alpha and leptin in obesity and insulin resistance: a
hypothesis on the impact of physical exercise.
AB - Obesity is associated with an increased incidence of insulin resistance,
dyslipoproteinemia, and hypercoagulability. In a more recently established
hypothesis of body weight control and regulation of metabolism, the adipocyte
secretes leptin and locally expresses TNF-alpha, the latter being responsible for
the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression
and TNF-alpha protein are greatly increased in adipose tissue from obese animals
and humans. Elevated TNF-alpha expression induces insulin resistance by
downregulating the tyrosine kinase activity of the insulin receptor and
decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces
lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis,
and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover,
adipocytes secrete leptin, a molecule with a secondary cytokine structure whose
concentrations correlate with the amount of fat tissue. Increased leptin levels
downregulate appetite and increase sympathetic activity and thermogenesis in the
hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and
serum leptin levels and is associated with improved insulin sensitivity and lipid
metabolism. Although exercise has also been shown to reduce leptin levels, an
influence on TNF-a expression in adipocytes or muscle cells has not yet been
demonstrated.
PMID- 9644111
TI - Diacylglycerol molecular species in plasma membrane and microsomes change
transiently with endothelin-1 treatment of glioma cells.
AB - Agonist-induced intracellular signal transduction often involves activation of
protein kinase C by diacylglycerol (DAG) released from membrane phospholipids by
phospholipases. Using either DAG kinase or HPLC assays to quantitatively
determine DAG mass, we observed a time-dependent increase in DAG accumulation
upon incubation of rat C6 glioma cells with 200 nM endothelin-1 (ET-1). Total
cell DAG rapidly increased by 25-35% from a basal level of 4.5 +/- 0.3 nmol/mg
protein during one min of ET-1 treatment and remained constant or slightly
decreased between 1 and 2 min. Thereafter, DAG increased to a maximum (1.6-fold
above basal) by 5-10 min. and remained elevated to 30 min. Resolution of DAG
molecular species by HPLC after incubation of cells with ET-1 revealed that
accumulation of DAG species differed in total cell lysate and subcellular
compartments. In plasma membrane, major DAG species increased at 1 min. followed
by a decrease at 10 min. whereas in microsomes DAG species did not change at 1
min. and decreased at 10 min. Although phospholipid sources of DAG species were
not identified specifically, there was preferential hydrolysis of molecular
species of phospholipid for DAG production. We propose that molecular species of
DAG produced at the plasma membrane may be transferred to the endoplasmic
reticulum so that phospholipid resynthesis can replenish molecular species
initially utilized in signal transduction.
PMID- 9644112
TI - Effects of systemic prostaglandin E1 on splanchnic and peripheral haemodynamics
in control subjects and in patients with cirrhosis.
AB - Prostaglandins of the E series showed metabolic and clinical effects in patients
with liver disease; changes in splanchnic haemodynamics might be involved. Blood
flow in femoral and mesenteric artery and in the portal vein was measured by echo
Doppler in 10 controls and 14 cirrhotic patients, in response to the systemic
infusion of a PGE1 analogue (30 micrograms/h for 2-6 h) or saline, performed in
random order. Intraparenchymal resistive and pulsatility indices in the liver,
spleen and kidney were also measured. In both groups PGE1 increased femoral
artery flow by 40%, irrespective of infusion time. Heart rate increased slightly,
whereas mean arterial pressure decreased. There were no changes in mesenteric
artery and portal vein flow, as well as in resistance indices. Saline infusion
increased femoral artery flow by 4%. PGE1 infusion does not produces significant
effects on Doppler-assessed splanchnic hemodynamics in controls and in cirrhotic
patients, in spite of significant effects on peripheral circulation.
PMID- 9644114
TI - Effects of Lorenzo's Oil on peroxisomes in healthy mice.
AB - We investigated peroxisomal alterations in mice treated with different doses of
Lorenzo's Oil (a therapy for X-linked adrenoleukodystrophy patients) for up to
100 days. Hepatic erucic acid levels were already significantly increased 2.2
fold and 2.6-fold in mice treated with 10% and 20% Lorenzo's Oil for 21 days,
respectively. No lipidosis was found in liver, myocardium and kidney of any of
the treated mice. While hepatic catalase, lauroyl-CoA oxidase and glycolate
oxidase, and renal catalase activities were not induced by either diet,
myocardial catalase activity was increased in most groups. This suggests that the
mechanism of the effect of Lorenzo's Oil in X-linked adrenoleukodystrophy
patients may not be a direct effect on the peroxisomes.
PMID- 9644113
TI - Effects of oxysterols upon macrophage and lymphocyte functions in vitro.
AB - Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations
in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell
responses to different stimuli. The action of oxysterols on macrophage functions
and macrophage-lymphocyte interaction has been poorly investigated. In this work,
the effects of 25-hydroxycholesterol (25-OHCh) and 7-ketocholesterol (7-KCh) upon
some functions of murine peritoneal macrophage (PM), such as generation of
reactive oxygen intermediates (ROI), secretion of neopterin and interleukin-1 (IL
1)-like activity, Fc-receptor (FcR) activity, and murine and human lymphocyte
functions, participating in lymphocyte-macrophage interactions, such as
macrophage-activating factor (MAF) and Ia-inducing factor (IaIF) secretion, were
studied in vitro. 7-KCh in concentration of 5 micrograms/mL culture medium only,
but not 25-OHCh, significantly inhibited ROI generation by zymosan-stimulated PM.
Pretreatment of PM for 22 h with 25-OHCh and 7-KCh led to the decrease of IL-1
like activity secretion. 25-OHCh and 7-KCh inhibited both FcR-dependent binding
and phagocytosis of sheep red blood cells (SRBC). Oxysterols did not change both
spontaneous and lipopolysaccharide-stimulated secretion of neopterin by PM. 25
OHCh dose-dependently and more efficiently than 7-KCh inhibited murine splenocyte
secretion of MAF, which activity was determined by the ability of splenocyte
conditioned medium to stimulate ROI generation in PM. Both 25-OHCh and 7-KCh
inhibited significantly proliferative activity of human mixed lymphocyte culture
(MLC), as well as lymphocyte secretion of IaIF, which stimulates the expression
of HLA antigens in cultured human monocytes. Purified Ch did not alter these
parameters. These data showed, that some inflammatory functions of macrophages
and lymphocytes may be modified by such environmental conditions as the presence
of oxysterols.
PMID- 9644115
TI - Polyphosphoinositide synthesis in human neutrophils. Effects of a low metabolic
energy state.
AB - Phosphatidylinositol (PtdIns) synthesis and polyphosphoinositide (PPI) formation
were measured as the incorporation of [32P]orthophosphate ([32P]Pi) or
[3H]inositol into non-stimulated intact human neutrophil membrane phospholipids.
The rate of PtdIns "de novo" synthesis appeared to be a slow mechanism when
compared to the rapid incorporation of [32P]Pi into PPIs. Of the "de novo"
synthesized [3H]PtdIns, 70% was further phosphorylated to PPI. Nevertheless, this
PPI pool represented less than 0.01% of the total nmols of PPIs formed evaluated
as [32P]Pi labeling, indicating that PPI formation mainly involves a no "de novo"
synthesized phosphatidylinositol pool. When evaluated at short incubation times,
oscillations in the formation of PPIs were detected. A rapid phase was
characterized after 30 s of incubation with [32P]Pi Phosphorylation levels
returned to an equilibrium state within a minute, and the second phase peaked at
5 min., returning to equilibrium at 15 min. The fluctuant kinetics though not the
equilibrium level of PPI formation, could be abolished by neomycin. On the other
hand, a selective inhibition of the rapid phase of PPI synthesis occurred in the
presence of the tyrosine kinase inhibitor genistein. When the incorporations of
[gamma-32P]-adenosine triphosphate (ATP) or [32P]Pi into human neutrophil
particulate fraction membranes were evaluated, PPIs synthesis showed fluctuations
independently of the precursor used. Noticeably, [32P]from [32P]Pi was
incorporated more efficiently into PPIs than that from [gamma-32P]ATP, when
evaluated in parallel using equal specific activities for both radiolabeled
precursors and under non-ATP synthesizing conditions. Moreover, the incorporation
of [32P]Pi into particulate fraction PPIs was not abolished by high
concentrations of non-radiolabeled ATP, and metabolically inhibited PMNs showed
high rates of PPI synthesis. These data suggest that PPI formation is not
necessarily a futile cycle in PMNs.
PMID- 9644116
TI - Multiresistance and 'superbugs'.
PMID- 9644117
TI - Keeping the customer satisfied.
PMID- 9644118
TI - The United Kingdom's hepatitis B immunisation strategy--where now?
AB - The World Health Organization recommended in 1992 that all countries should
introduce universal hepatitis B vaccination into their immunisation schedules by
December 1997. Over 80 countries, many of them in western Europe, have complied
with the recommendation, but, in the United Kingdom (UK), hepatitis B vaccine is
offered to selected high risk population groups only. Vaccination uptake in many
of these groups is poor and transmission of hepatitis B remains a problem. The
current incidence of hepatitis B is lower in the UK than in countries that have
adopted a universal approach. It is impossible, however, to predict the number of
acute infections that might occur in an unvaccinated teenage population in the
year 2015 if the UK's current strategy remains unaltered. Universal immunisation
would guarantee that hundreds, if not thousands, of acute illnesses and an
appreciable number of severe outcomes would be prevented each year. The authors
believe that funding this intervention would be money well spent.
PMID- 9644119
TI - Complications of bacille Calmette-Guerin (BCG) vaccination and immunotherapy and
their management.
AB - Complications of bacille Calmette-Guerin (BCG) vaccination are uncommon. Fewer
than one in 1000 people vaccinated develop significant local reactions, and
serious disseminated disease develops in fewer than one in a million. Localised
complications--which include hypersensitivity reactions, abscesses at the
injection site, and localised lymphadenopathy--are usually self limiting. They
usually result from faulty technique, including the accidental intracutaneous
injection of the stronger percutaneous vaccine, or poor selection of subjects for
vaccination. Abscesses at the injection site usually respond to drainage and
chemotherapy with isoniazid or erythromycin. Lymphadenopathy responds poorly to
antimicrobial treatment and surgery may be needed for suppurating or discharging
lesions to hasten recovery and give a good cosmetic result. Disseminated disease
usually occurs in people with impaired immunity, in whom it is often fatal. BCG
should never be given to people who are known to be infected with HIV, but the
risk of complications in children born to HIV infected mothers is low.
Disseminated disease can also result from intravesical instillation of BCG to
treat bladder cancer, but this responds to antituberculosis chemotherapy.
PMID- 9644120
TI - Laboratory surveillance of hepatitis C virus infection in England and Wales: 1992
to 1996.
AB - Screening assay for antibody to hepatitis C virus (HCV) became available late in
1990 and their use has subsequently become widespread. Laboratories in England
and Wales reported 5232 confirmed HCV infections to the PHLS Communicable Disease
Surveillance Centre (CDSC) between 1992 and 1996. Fifty-seven per cent (2976) of
reports included risk factor information, 80% of which (2382) identified
injecting drug use as the main route of transmission. Thirty-one per cent of
reports (1640) included clinical information: 41% (665) were asymptomatic, 57%
(938) had symptoms, signs, or biochemical abnormalities of hepatic origin, and
2.2% (37) had non-hepatic conditions. To enhance these data two additional
surveys have been undertaken to collect data on all anti-HCV tests performed in
public health laboratories. In 1993, a retrospective survey of people tested
between 1990 and 1993 revealed that the prevalence of antibody was highest
(222/331 [67%]) among injecting drug users and recipients of blood or blood
products (189/548 [34%]) and lower among other groups. In a prospective survey of
HCV tests performed in transfusion recipients in early 1995, the prevalence of
antibody was higher in those transfused before 1985 (11/418 [2.6%]) than in those
transfused after 1985 (14/1441 [1.0%]). Reports of confirmed infections are a
useful method of monitoring hepatitis C infection but additional data on testing
are needed to interpret trends overall and in specific risk groups.
PMID- 9644121
TI - Hepatitis C virus antibody prevalence among injecting drug users in Glasgow has
fallen but remains high.
AB - Few data have been published on the prevalence of hepatitis C virus (HCV) among
injecting drug users (IDUs) in the United Kingdom. This study compares the
prevalence of antibody against HCV (anti-HCV) among IDUs in Glasgow in 1990 (when
Glasgow's needle/syringe exchange programme had become established) with that in
1995. Serum left over from specimens taken for named HIV antibody testing was
tested anonymously for anti-HCV. The prevalence of anti-HCV fell significantly
between 1990 and 1995 among IDUs of all ages (90% to 77%), IDUs aged 15 to 19
years (92% to 29%), and IDUs aged 20 to 24 years (91% to 65%). This study
suggests that the incidence of HCV infection among young IDUs fell in the early
to mid 1990s, after the establishment of Glasgow's needle/syringe exchange scheme
between 1988 and 1990. Since almost a third of injectors under 20 years of age
when tested in 1995 had been infected with HCV, however, other interventions may
be needed to prevent the spread of HCV in this high risk group.
PMID- 9644122
TI - Occupationally acquired infectious disease in the United Kingdom: 1996 to 1997.
AB - The incidence of occupationally acquired infectious diseases, has, up to now,
been unknown. A reporting scheme for consultants in communicable disease control
(CCDCs) (and their equivalents) throughout the United Kingdom was set up in
October 1996 to estimate its extent. Monthly reporting cards were sent to CCDCs
asking for brief details of all new cases of occupationally acquired infectious
disease seen by them. Between October 1996 and September 1997, 1037 new cases
were notified by CCDCs. The highest rates were among employees in food production
and catering, farming, and among care workers, particularly in residential homes.
During the same period an estimated 257 cases were reported in comparable
surveillance schemes by chest physicians, occupational physicians and
dermatologists. These figures probably underestimate the number of infections
acquired in association with work substantially, and highlight diarrhoeal disease
as the commonest problem.
PMID- 9644123
TI - Occupational acquisition of HIV infection among health care workers in the United
Kingdom: data to June 1997. Local Collaborators, PHLS AIDS and STD Centre,
Scottish Centre for Infection and Environmental Health.
AB - Transmission of HIV infection to health care workers in the work place through
percutaneous or mucocutaneous exposure to blood or blood stained fluid remains
rare, but it is important for countries to publish updates of cases of HIV
infection thought to be occupationally acquired. The last update for the United
Kingdom (UK) summarised data to the end of 1992; this paper summarises cases
reported to have occurred by June 1997. Four HIV infections classified as
'definite' occupational acquisitions had been reported in the UK by 1993. No
further cases in this category have been reported since, but the number of
"possible" occupationally acquired cases has risen from six to eight. Seven of
the 12 definite and possible cases reported worked as nurses, four were doctors
(of whom two were surgeons), and one was a phlebotomist. Seven of the
transmissions were thought to have occurred in sub-Saharan Africa. Passive
reporting of exposures to HIV was replaced by a more active reporting system in
July 1997 in which occupational health departments are contacted regularly.
PMID- 9644124
TI - Unusual HIV transmissions through blood contact: analysis of cases reported in
the United Kingdom to December 1997.
AB - It is important to establish the likely route of infection for all reported HIV
infected individuals if the HIV epidemic is to be understood. Investigating
routes of infection may bring unusual infection routes to light. Steps have been
taken in the United Kingdom (UK) to establish the likely mode of HIV acquisition
for everyone reported as infected. If an initial report is incomplete the
clinician caring for the patient is asked for relevant information. If further
information is needed, and an interview is feasible and acceptable to both the
clinician and the patient, information is collected from the patient through face
to-face semistructured interview. Such follow up has identified 19 cases (among
34,000 records of individuals with HIV and/or AIDS for which probable routes of
infection have established) who seem to have acquired HIV infection in unusual
circumstances. Seven of the 19 cases described in this paper are thought to have
acquired HIV infection in the UK, two in Spain, and ten in countries with a high
prevalence of HIV infection. This paper describes the circumstances in which HIV
transmission is believed to have occurred.
PMID- 9644126
TI - Whooping cough surveillance in the north west of England.
AB - The number of whooping cough notifications has declined in recent years, as
vaccine coverage has recovered from the low levels seen in the 1970s and 1980s.
Notification of infectious disease is often incomplete, and this study aimed to
estimate the extent to which whooping cough is undernotified. We included all
cases of whooping cough occurring in the North West Region between 1 April 1994
and 31 December 1996, identified by notification, hospital admission data, or
laboratory reports. By combining the three sources, 1239 cases were identified,
69.6% of which were notified. The notification rate was 29.6% (131/442) for cases
admitted to hospital and 45.6% (78/170) for laboratory reported cases.
Completeness of notification was estimated to be 35.7% (863/2420; 95% confidence
interval 30.3-43.4%) using the capture-recapture method. The study confirms that
notification of whooping cough is incomplete and suggests that two thirds of
cases are not notified.
PMID- 9644125
TI - Enhanced surveillance of acute symptomatic hepatitis B in England and Wales.
AB - A prospective incidence study was used to estimate the effect on transmission of
hepatitis B virus (HBV) in England and Wales of maximising uptake of HBV
vaccination in patients at risk attending genitourinary medicine (GUM) clinics or
any medical services. Laboratory based surveillance in 1993 gave an incidence of
acute symptomatic hepatitis B of 1 case per 100,000 population. Transmission
through sexual intercourse was twice as common as through injecting drug use.
Less than 20% of patients with acute HBV infection had attended a GUM clinic
before their illness, but 42% had had access to other medical services where
vaccination could have been offered routinely. Sixty per cent of patients' sexual
partners and 37% of other members of their household had been offered
vaccination. Compared with universal infant or pre-adolescent vaccination,
extending the current selective policy to all who attend GUM clinics or any
medical services would have a limited impact on the incidence of HBV,
particularly as uptake of three doses of vaccine in adults is likely to be low.
PMID- 9644127
TI - Molecular characterisation of methicillin resistant Staphylococcus aureus.
AB - Finer discrimination between strains of methicillin resistant Staphylococcus
aureus (MRSA) than phage typing can provide is needed to identify and
characterise spread of infection in outbreaks. This study compares three
molecular methods with each other and with phage typing. Pulsed field gel
electrophoresis provides the greatest discrimination, but finer discrimination is
obtainable by combining methods.
PMID- 9644128
TI - How well do viruses survive during transport?
AB - Centralisation of viral diagnostic services offers the potential for cost saving
in laboratories, but incurs costs for transporting specimens. In a trial of 326
paired specimens, isolation rates of viruses sent by overnight post and a more
expensive same-day courier service were similar.
PMID- 9644129
TI - Progress in the development of Helicobacter pylori strain typing methods.
AB - Helicobacter pylori is very different from other Gram negative bacteria that
inhabit the human gastroduodenal tract. Its success in adapting to colonise and
persist in the stomach is reflected in key features such as unique chemical
structure and architecture of lipopolysaccharide, sheathed flagella, genomic
diversity, and potent urease activity. Strain diversity within the species is
well established and so the challenge is to exploit variations in these features
for developing relevant epidemiological typing methods.
PMID- 9644130
TI - A user's guide to producing and interpreting tree diagrams in taxonomy and
phylogenetics. Part 2. The multiple alignment of DNA and protein sequences to
determine their relationships.
PMID- 9644131
TI - Noise at work.
AB - The word noise implies sound that is loud, disturbing, and unwanted. This article
reviews what can be done about noisy working environments within the context of
the established legal framework, as well as on a local practical level.
PMID- 9644133
TI - [A fast iterative algorithm for adaptive histogram equalization].
AB - In this paper, we propose an iterative algorthm called FAHE., which is based on
the relativity between the current local histogram and the one before the sliding
window moving. Comparing with the basic AHE, the computing time of FAHE is
decreased from 5 hours to 4 minutes on a 486dx/33 compatible computer, when using
a 65 x 65 sliding window for a 512 x 512 with 8 bits gray-level range.
PMID- 9644132
TI - [The development of CTTM-1000 distant electrocardiogram central ambulatory
monitoring system].
AB - This article introduces a new electrocardiogam telephone transmitting and central
ambulatory monitoring (receiving) system, and a device used for monitoring and
transmitting the user's electrocardiogram. We also give some detailed discussion
about the real time the flow display of ECG, and the signal preprocessing method
based on the design of optimum FIR linear phase digital filter for the detection
of QRS complexes.
PMID- 9644134
TI - [Research of system reliability on Model NXS X-ray image medical machine].
AB - In the paper, according to theoretic reliability analysis and experiment
research, the System Reliability of NXS X-ray image medical machine is studied by
a new computer digital simulation method. The practical method is mainly
suggested on its FTA model simulated by algorithm on a computer, then the
Reliability Probability, MTBF and Structure Importance on the machine are
obtained. The System Reliability results are discussed in detail finally.
PMID- 9644135
TI - [The development and efficacy tests for the autoclave indicator tape].
AB - The paper describes the development and efficacy teats for the autoclave
indicator tape which has specially effects on temperature of pressure steam, time
of persistence and air of remainder in the autoclave, and quick, simple and
advanced charater for indirectly testing the quality of autoclave sterilization.
PMID- 9644136
TI - [The development of a microcomputerized fetal electrocardiograph].
AB - A new microcomputerized Fetal Electrocardiograph (FECG) is presented in this
paper. A two-grade configuration (front-end & back-end) is designed for the
instrument. The front-end processor is based on a Digital Signal Processor (DSP)
TMS32010 and the Adaptive Noise Cancelling (ANC) algorithm to extract FECG with
non-invasive method. The processed results are sent to the back-end personal
computer for real time display, analysis and record. Clinical tests show the
instrument is designed smartly and operated easily, and can be applied widely to
many medical situations.
PMID- 9644137
TI - [The measurement of eye axial length by ultrasound].
AB - Ultrasonic biometer is the best method of eye axial length measurement now. In
this paper, our biometric method is introduced. It can measure the anterior
chamber depth, lens thickness, vitreous length and axial length automatically,
which are important to intraocular implant (IOL).
PMID- 9644138
TI - [A new method and instrument for brainlocal hypothermia].
AB - A new method and instrument for brainlocal hypothermia have been introduced in
this paper. The instrument provides hypothermia to cerebral blood circulation by
using cold probe hyperthemia to body venors blood by using electric heater. So it
reduces the temperature only local in brain. This therapy system provides a safe
and successful method for brain protection in wide clinical application, such as
brain injure emergency, cerebrovascular disease therapy, heart operation etc.
PMID- 9644139
TI - [The development of hematomanometer auto test instrument].
AB - This paper introduces the development of hematomanometer auto test instrument of
a news measurement standard. The hard-ware and soft-ware and the circuit
structure of it are described in detail.
PMID- 9644140
TI - [The development of model MI-921A automatic clinical electrotyte analyzer].
AB - A automatic clinical electrolyte analyzer, which based on ion selective
electrode, has been developed for the measurement of potassium, sodeum, chloride
and calcium in serum. In this paper, the analyzer's measuring principle is
described, its structure and the design of hardware and software are also given.
The analyzer has features of fast analysis, less sample consumption, high
accurancy and convenience in operation. Good results has been achieved.
PMID- 9644141
TI - [The data acquisition and handling system controlled by computer for static
charge along meridians in human].
AB - The change of static charge along meridian in human is relation to disease. A
computer controlled data acquisition used for acpoint static charge detection is
presented in this paper. This system supplied a practical method for researching
the relation between disease and static charge along meridians in human.
PMID- 9644142
TI - [The research and design of a constant flow pump for clinical ultrasonic
emulsification].
AB - A constant flow pump for clinical ultrasonic emulsification is developed,
According to request, its output rotational speed can be continuously changed
from 0 to 40 revolutions per minute. It can stably infuses emulsion to operating
area.
PMID- 9644143
TI - [Design of an digital electrical impedance plethysmograph].
AB - The design of an digital impedance plethysmograph capable of measuring tissue
impedance and volume change of the ateries during endsystole is reported, The
50KHz frequency impedance signal is sampled at its peaks and the envelope is used
to follow the volume change without phase sensitive demodulator. It makes
frequency and amplitude of the signal more stable and an improved signal to noise
ratio.
PMID- 9644144
TI - [Micro-particle image processing based on an artificial neuron network with fluid
properties].
AB - The form of macro-particle is a close successive region in two-valued micro
particle image, and the detection of microparticles is actually that of close
successive regions. Accordign to this theory, this paper present a new technique
for micro-particles detecting based on an artificial neuron network modeled on
the diffusing behaviour of real visual system, which has fluid properties. The
results of simulation on computer shew that this method is very effect.
PMID- 9644145
TI - [The study of DSX-I type microcomputer autometic control injector system].
AB - This paper studies the propulsive force of injector system controlled by 8031
single-chip microcomputer for Medical use By using one 8031 single-chip
microcomputer as a microprocessor, the minimal autometic control system is
constructed, which turns real-time control into reality. This product is a modern
appliance used in diagnostic imaging medicine, in design of which the advanced
instrument and electrical machinery are integrated into a unified structure. The
clinic data demonstrate that the contrast medium can be injected to patients with
rapidly and evenly. Dynamic CT Scanning can be intensified at any site of the
body. x-ray dose exposed and lobour intensity to the operator can be decreased
greatly, raise working efficiency.
PMID- 9644146
TI - [The development of x-ray machine mAs tester].
AB - The numeric readout mAs tester described in this paper has the advantage of
simple and practical structure. It is suitable for regulations and repairs of x
ray machine for clinical units.
PMID- 9644147
TI - [Immunohistochemical study of myoglobin deletion from myocardium in hemorrhagic
shock].
AB - Myoglobin (MB) deletion from myocardium in the case of hemorrhagic shock was
firstly studied by immunohistochemical and morphometry technique. The results
showed that there were different degrees of segmental deletion of MB from
myocardium in each case of hemorrhagic shock which has continued over an hour.
The significance of these changes in forensic medicine are discussed.
PMID- 9644148
TI - [Analysis and assessment of meperidine and normeperidine concentrations in
urine].
AB - In this study, urine concentrations of meperidine and normeperidine after a
single therapeutic dose of meperidine in 5 healthy volunteers have been measured
and compared the results to those in meperidine addicts. The results showed that
there was a significant difference between two groups in the ratio of metabolite
to parent drug. If can be concluded that the ratio should be aid in making a
cause of meperidine injection.
PMID- 9644149
TI - [Traumatic testis injuries in clinical forensic medicine: analysis of 5 cases].
AB - Five cases of traumatic testis injuries are reported. The effect of the testis
injuries on penile erectile ability and male fertility is reviewed. The problems
about the appraisal of the traumatic testis injuries in clinical forensic
medicine are discussed.
PMID- 9644150
TI - [Trauma and tumor: a report of 14 cases].
AB - In the present article, we report 14 cases of patients with different tumors,
injured or died after a traumatic episode. The relation between trauma and tumor,
and the associated problems in forensic medicine are discussed.
PMID- 9644151
TI - [Immunohistochemical study on myoglobin in electrocution].
AB - We have studied the changes of myoglobin (MB) IN heart muscle cells from eight
corpses died of electrocution. The changes were compared with that of the heart
muscle cells died of fall. The results indicated that the immunohistochemical
changes of Mb were as follows: (1) blocky separate from heart muscle cell; (2)
drift away into the interval of the heart muscle. The Mb changes were small parts
of an area separate from heart muscle cells in control. The authors emphasized
these changes were the characteristics of oxygen deficiency of the heart by
electrocution.
PMID- 9644152
TI - [Distribution of clozapine in poisoned rabbits].
AB - The distribution of clozapine in the body of rabbits died of poison was studied
by the method of TLC. The concentration of clozapine in blood, urine, bile,
livers, kidneys, spleen, lungs, hearts and brains were 19.4 +/- 6.9, 50.2 +/-
12.6, 75.9 +/- 12.5, 25.9 +/- 4.0, 34.0 +/- 4.7, 13.3 +/- 2.2, 20.0 +/- 4.3, 5.0
+/- 2.3 and 43.6 +/- 43.4 ug/ml or ug/g.respectively. It is concluded that the
Clozapine be not well-distributed in poisoned rabbits, Blood, bile, urine, liver
and spleen are better samples for the analysis of clozapine than others.
PMID- 9644153
TI - [Simultaneous detecting of C3 phenotypes and C3 cleavage by immunofixation].
AB - The C3 phenotypes and C3 cleavage were simultaneously detected using cellulose
acetate electrophoris followed by immunofixation and desitometry. Compared to
crossed-immunoelectro-phoresis, this method has some advantages in resolution
between different bands and was much more rapid, less expensive and more
sensitive.
PMID- 9644154
TI - [Usage of double immuno-enzyme labeled staining method in forensic pathology].
AB - In this paper we report a kind of double immunoenzyme labelled staining method
(single enzyme method). The principle of the method is that HPR will show blue
black color when it meet DAB-CoCL2/H2O2, while it will show brown color as it
meet DAB/H2O2, two colors constract very remarkably. This method was used to
detect the antigens of hearts and brains which obtained from forensic autopsy.
The results showed that the method was sensitive, simple and economical. One of
the advantages is that the stained sections can keep for a long time. Thus, is
very practical for forensic pathology.
PMID- 9644155
TI - [Pathological study in sudden death of primary cardiomyopathy: a report of 19
cases].
AB - A series of 19 cases of sudden death caused by primary cardiomyopathy were
investigated. The problems of diagnosing primary cardiomyopathy were discussed.
PMID- 9644156
TI - [Analysis of poisoned substances in hair].
PMID- 9644157
TI - [Ageing changes of the cardiac conduct system].
AB - This paper reviews the ageing changes of the human cardiac conduction system
according to the ever published literature. In ageing process, the cardiac
conduction system shows typical physiological changes: (1) differentiation,
development and maturation in fetal and postnatal period, (2) reduction of the
specific conduction cells and the changes of the whole node volumes. (3) fibrosis
and fat infiltration. It is stressed that while explaining the causes of sudden
death with the knowledge of cardiac conduction system diseases, the forensic
pathologist should be able to distinguish the pathological changes from that of
the normal ageing.
PMID- 9644158
TI - [A quantitative study on the cells of cochlear nucleus in rats at different
ages].
AB - The volume of cochlear nucleus and nucleolus, neural populations were determined
in rats of three groups aged (1, 2-3, 22-28 months). The study data indicated
that there is no difference between the volume of cochlear nucleus in the aged
and adult animals (P > 0.05). Compared with the other two groups, the aged
animals show a reduction of volume of necleolus of cochlear nucleus neurons (P <
0.01), a loss of neurons (spherical cell and multipolar cell) (P < 0.01). On the
other hand, it shows an increase in number for the glial cells in the aged
animals (48.48%, P < 0.01). Quantitative results of the cell of cochlear nucleus
were analysed. We suggest that central changes also play an important role in
presbycusis.
PMID- 9644159
TI - [Dissociation and culture of primary auditory neurons in postnatal chicken].
AB - In the present study, a primary culture of auditory neurons in 10-16-day old
chickens was carried out. We observed the morphologic features of auditory
neurons at different culturing stages by using phased-contrast and scanning
electron microscope, and particularly described their growth and developmental
process. The results indicated that a steady and reliable culturing method
established here would contribute to the biological research of inner ear in
vitro.
PMID- 9644160
TI - [Computed tomography of the anterior ethmoid sinuses and its adjacent structures
for endoscopic sinus surgery].
AB - Forty adult cadavers were examined by computed tomography (CT) imaging with
special attention to the pneumatization of the anterior ethmoid sinus for
endoscopic sinus surgery. The study of the specimen was done using coronal
section and axial section, sagittal reconstructed images were obtained from the
data acquired in the axial plane. The cells of anterior ethmoid sinus were
classified into four sub-groups, namely, the pre-infundibular cell (appearance
rate 87.5%), the lateral infundibular cell (82.7%), the post-infundibular cell
(86.3%) and the bulla cell (100.0%), and the anterior ethmoid sinus was
classified into two types, namely, intraethmoid type (71.2%) and extraethmoid
type (28.8%). The results shows that CT can display the sub-group and the type of
the anterior ethmoid sinus and its adjacent structures clearly. The significance
of endoscopic sinus surgery was discussed.
PMID- 9644161
TI - [Carotid body tumor (report of 4 cases)].
AB - Four cases of carotid body tumor are reported, and the diagnosis and treatment
are also discussed. We consider that color Doppler flow image and carotid
angiography, especially digital subtraction angiography, are of great value to
the diagnosis of carotid body tumor. In addition, the collateral cerebral cross
flow was promoted preoperatively with the use of compressing exercises of the
carotid artery, and controlled by transcranial Doppler. This means to provide the
basis for choosing the operative opportunity and for managing the carotid artery.
The operative method was dependent on preoperative color Doppler flow image,
carotid angiography, and relationship between the tumor and the carotid artery
during operation.
PMID- 9644162
TI - [Infective factors of adult secretory otitis media].
AB - There were histories of the upper expiratory tract infection in 49 out of 86
cases in adult secretory otitis media (SOM). Among them, thirty two cases were
administrated antibiotics a week ago when the effusions were collected. The
patient's Eustachian tubes in twenty nine cases were clinically ventilated. The
endotoxins were positive in 39 out of 86 specimen tested with limulus assay,
among these specimen, bacteria were cultured from 11 specimen. The data exibited
that the appearance of the SOM is related to the existence of the infective
factors in the middle ear cavity. The upper expiratory tract infection before the
onset of the middle ear effusions is one of the important causes inducing the
disease. The lower rate of bacteria culture than that of endotoxins is related
with the administration of antibiotics before the onset of the disease. The
administration of antibiotics in the treatment of the middle ear effusions will
help to elimilate bacteria in the cavity of the middle ear effusions, improve the
ventilating function of the Eustachian tube and make the effusions turn to
disappearance.
PMID- 9644163
TI - [Digital subtraction angiography and selective arterial embolization in the
treatment of vascular tumors in nasopharynx and nasal sinuses].
AB - The paper presents the treatment of vascular tumors in nasopharynx and nasal
sinuses with digital subtraction angiography (DSA) and selective arterial
embolization. By using preoperative embolization of blood supply arteries, the
intraoperative bleeding was reduced significantly, the tumors were shrank and the
tumor limits were clear. We recommend that DSA and selective arterial
embolization should be used as a routine preoperative method adjunct to surgery
for the treatment of vascular tumors of nasopharynx and nasal sinuses.
PMID- 9644164
TI - [Study of the expression of the epidermal growth factor-receptor in the laryngeal
squamous cell carcinoma and the correlation with clinical pathology
characteristics].
AB - OBJECTIVE: The expression of the epidermal growth factor-receptor (EGF-R) in the
laryngeal squamous cell carcinoma and the correlation with clinical
characteristics of the tumor, difference of tissues. METHOD: Immunohistochemical
detection. RESULTS: The EGF-R expression was evaluated in 36 laryngeal squamous
cell carcinoma and 25 normal laryngeal tissues specimens. The EGF-R expression
showed only in one specimen of normal laryngeal tissues, whereas twenty-four of
thirty-six carcinomas showed positive staining reaction with the anti EGF-R
antibodies. The EGF-R expression did not correlate with age, whereas it was
higher in poorly differentiated tumors than in moderately and well differentiated
tumors (P < 0.05) and it was higher in T3, 4 of TNM classification than in T1, 2
(P < 0.05). Four patients being the recurrence cancers after the operation had an
enhanced expression of EGF-R. Six of seven patients with the metastatic
cervicallymph-node involvement showed an enhanced expression of EGF-R.
CONCLUSIONS: The uncontrolled cell growth and proliferation of the laryngeal
squamous cell carcinomas may be related to the abnormal EGF-R expression. The
enhanced expression of EGF-R can be identified as a poorly prognostic parameter.
PMID- 9644165
TI - [The treatment of nasopharyngeal carcinoma by using thermoradiotherapy].
AB - The treatment effect of radiotherapy combined with local hyperthermia for
nasopharyngeal carcinoma was studied in 23 patients. In 24 cases of the control
group (radiotherapy), conventionally dynamic fractionation of dose was used. At
40 Gy, the regression of tumor was observed 83% in the study group and 54% in the
controls group. No severe complications in patients treated by thermotherapy were
noted. This paper discusses the role and the mechanism of local hyperthermia as a
rediomodifying factor.
PMID- 9644166
TI - [Study of optimal parameters and normal values for auditory P300].
AB - Study of optimum seeking method with orthogonal test for auditory P300 measuring
was carried out in healthy adolescents. The result showed that the optimal
conbination of parameters was as follows: stimulus sound was Logon, recording
electrode site Cz, analysis time 750 ms, average 100, stimulus rate 1 c/s, target
stimulus (TS) probability 10%, bandpass filter 1-50 Hz, non-target stimulus (NTS)
freqency 1 kHz, target stimulus (TS) frequency 2 kHz, stimuli intensities 110 dB
peSPL. The normal values of auditory P300, obtained from 30 healthy adolescents,
including latencies and amplitudes, were measured under optimal parameters. P300
latency was about 310 ms, RT about 258 ms, these two values present a significant
linear correlation.
PMID- 9644167
TI - [Study on the relation between HPV and tumors of the throat and larynx].
AB - HPV structural antigens and HPV 6, 11, 16, 18 DNA sequences were detected with
immunohistochemical staining and DNA dot blot hybridization in papillomas and
squamous cell carcinomas of the throat and larynx. The positive rates of HPV
antigens and HPV DNA sequences in 11 cases of papillomas were 45.5%,
respectively, while the positive rates of HPV in 22 cases of squamous cell
carcinomas were 22.7% and 27.3% respectively. The positive rates of HPV were in
accord with those by histologic study in papilloma. The results indicate that the
papillomas and squamous cell carcinomas of the throat and larynx may be related
with HPV infection.
PMID- 9644168
TI - [The relationship between histologic grading of malignancy and regional lymph
node metastasis in squamous cell carcinoma of larynx].
AB - Forty cases of squamous cell carcinoma of larynx have been studied by using five
factors scale in order to investigate the relation between histologic grading of
malignancy and regional lymph node metastasis. The results show that high degree
malignancy tumor (which gets more than ten points) and diffusly invased tumor
have a significantly higher proportion of regional lymph node metastasis than
others. There was no relation between histologic grading of malignancy and T
categories. It indicated that histologic grading of malignancy may be a good help
in predicting patient evolution.
PMID- 9644169
TI - [Hyaluronic acid-streptomycin perfusion of the labyrinth through the round
window].
PMID- 9644170
TI - [Distortion product otoacoustic emissions on neonates].
AB - Distortion product otoacoustic emissions (DPOAE) is evoked by two pure-tones (f1,
f2). It is a kind of reflex of cochlea. In order to know the effect of different
elements on DPOAE of neonates, we used GSI 60 DPOAE to detect the DPOAE of 40
ears of 20 neonates. The results showed that when f1 was below 1,000 Hz, the
incidence of DPOAE was very low. When the f1 was between 1,400 and 4,000 Hz, the
incidence of detectability was more than 90%. The amplitude of DPOAE was low
within lower frequency area, while f1 was between 1,000 and 4,000 Hz, the
amplitude was higher. We consider that the DPOAE of neonates were easily affected
by noise, stimulus intensity, the function of middle ear, etc. We must pay
attention to these elements when we use DPOAE to test hearing function of
neonates.
PMID- 9644171
TI - [Mondini's deafness].
AB - Mondini's deafness was the congenital malformation of inner ear. We studied 199
ears of 106 cases. Most of them were found deaf when they were babies. High
resolution computed tomography of temperal bone was described: cochlea
malformation 4 ears; malformation of cochlea, vestibule and semicircular canal 90
ears; vestibular of semicircular malformation without cochlea malformation 105
ears, this type was called the vestibule malformation or untypically Mondini's.
Of all the 199 ears there were 81 ears with enlargement of the vestibule
aqueducts. The pathogeny, clinical manifestation and treatment were discussed.
PMID- 9644172
TI - [Cross susceptibility of ototoxicity about aminoglycoside antibiotics].
AB - A familial investigation was made in three families with deafness patients caused
by aminoglycoside (AMI). The results showed that there was cross susceptibility
among a few AMI antibiotics. The people with familial history of deafness caused
by AMI were easier to be toxic than those without familial history, even though
little dose of AMI for the former, especially for children. The cross
susceptibility is dominated by inheritance of matriarchal heredity and by general
chromosome. The data suggest that medical history should be inquired before
treatment with AMI, and patients with matriarchal heredity must be prohibited
from using AMI.
PMID- 9644173
TI - [Application of otoadmittance to measure eustachian tube tympanometry].
AB - This paper studied a simplified and quantified valsalva and reverse valsalva
maneuver eustachian tube tympanometry with otoadmittance meter. In normal groups,
the compliance changes were 0.57 +/- 0.23 ml with valsalva maneuver and 0.26 +/-
0.12 ml with reverse valsalva maneuver. Otherwise, the recordings were performed
in various tympanic functions induced by various eustachian tube functions, and
the results showed that this method was significant for the diagnosis of
eustachian tube structure, obstruction or patency. The recording curves helped to
determine the types and degrees of eustachian tube abnormality.
PMID- 9644174
TI - [Intranasal endoscopic ethmoidectomy and the analysis of curative effect].
AB - Forty cases of intranasal endoscopic ethmoidectomy were analyzed. In this series,
28 males and 12 females were included. Hard endoscopes with diameter of 4 mm,
visual angle 30 and 70 were used. All patients were followed-up for 3 to 12
months. The surgical results were that twenty percent of patients were completely
relieved of symptoms, 10% symptom-free with additional therapy, 40% improved
without additional therapy, 20% improved with additional therapy, 10% no
improvement and the total effective rate was 90%. No operative complications
happened. Some factors affecting operative effects were discussed.
PMID- 9644175
TI - [Endoscopic sinus surgery through the front wall of maxillary sinus: report on 30
cases].
AB - By drilling the front wall of maxillary sinus, endoscopic sinus surgery was
performed in 30 cases. Using this method, the focus was easily observed and
cleaned, the natural hole was rapidly and reliably reamed with less bleeding and
no serious reaction, and the rate of recurrence was lower.
PMID- 9644176
TI - [Tumours of the nose and sinuses presented as nasal polyp].
AB - Twelve cases of tumours of the nose and sinuses misdiagnosed at the first time as
nasal polyp are reported. Of them, 4 were benign and 8 malignant. The endoscopic
technique is helpful to differential diagnosis of benign or malignant lesions and
polyps in these areas.
PMID- 9644177
TI - [Embryogenesis and functional development of the chick's basilar papilla].
PMID- 9644178
TI - [The application of transmeatal exploratory tympanotomy].
AB - Transmeatal exploratory tympanotomy has been used traditionally for the surgical
treatment of conductive deafness. With 8 cases of the middle and inner ear
diseases diagnosed and surgical managed successfully with this approach, the
extended applications of this procedure were illustrated, which included: 1.
conductive deafness with cause undetermined, 2. post traumatic conductive
deafness with intact tympanic membrane, 3. suspected primary space occupying
lesion of tympanum. 4. perilymphatic fistula, and 5. cerebrospinal fluid
otorrhea. The key consideration and advantage of this approach were also
discussed in this paper.
PMID- 9644179
TI - [Malignant changes in laryngeal papilloma with 13 case reports].
AB - The 13 cases of malignant changes in 43 cases of laryngeal papilloma are
reported. The rate of malignant change was 30. 2%. Laryngeal papilloma with
epithelial atypia has proclaimed the onset of carcinoma. Therefore, high
attention should be paid on its treatment. The safe margin on the operation of
the malignant change case should be kept above 0.5 cm and radiation should be
followed after the operation. It was invalid by using only radiation treatment.
The pathogenesis and diagnosis of malignant change in laryngeal papillomas were
also discussed in this article.
PMID- 9644180
TI - [The use of platysmal myocutaneous flaps in laryngeal reconstruction].
AB - Vertical frontal subtotal laryngectomy, a procedure that can remove as much as
90% of the larynx, was used to produce a functionally acceptable neolarynx with
platysmal myocutaneous flaps. Thirty-two patients with laryngeal carcinoma
underwent this operation. All flaps survived and there was no necrosis after
operation. With the exception of one patient who require nasal feeding because of
an irritating cough when swallowing food, all the other patients regain
breathing, swallowing and phonating of laryngeal function. The operative methods,
advantages and experiences are discussed in this paper.
PMID- 9644181
TI - [Determination of complements in serum and middle ear effusion of the patients
with secretory otitis media].
AB - Complements in serum and middle ear effusion were determined in 20 patients with
secretory otitis media, and compared with those in the normal controls. The C5
and C1-INH in serum of the patients were significantly higher. On the contrary,
C9 and B factor (Bf) were significantly lower, and the circulatory immunocomplex
was also higher. In patients with secretory otitis media, the middle ear effusion
levels of C3, C4 and C5 were significantly lower, and Bf and immunocomplex were
significantly higher than those in serum. The results suggest that the ability of
complements in clearing immunocomplex is low. Therefore, the immunocomplex may
deposit in the mucosa of the middle ear. Thus the permeability of capillary will
be increased, and the middle ear effusion occurs.
PMID- 9644182
TI - [Ultrastructural study of tumor infiltrating lymphocyte in tissues of laryngeal
squamous cell carcinoma].
AB - By transmission electron microscopy tumor infiltrating lymphocyte (TIL) in
laryngeal squamous cell carcinoma tissues of 14 cases was studied. The results
showed that the infiltrating lymphocyte in varying degrees eristed in laryngeal
squamous cell carcinoma tissues. Most of them were present in a motionless state,
and the others showed the feature of activated metrocyte and closely contracted
with cancer cells and resulted in distinct morphological changes both the cancer
cells and themselves. Therefore, this study provided an important morphological
evidence for TIL as killer and inhibiter to the growth of cancer cells.
PMID- 9644183
TI - [Kaposi's sarcoma associated with HIV in otorhinolaryngology: report of 21
cases].
AB - Twenty one cases of kaposi's sarcoma (KS) with manifestation in the field of
otolaryngology are reported. The incidence of KS is increasing following epidemic
of AIDS all over the world. Epistaxis, nasal obstruction, sore-throat, dry of
foreign body filling in throat and nodal mass are most frequent manifestation.
The relationship of KS with HIV, it's pathology and diagnosis are discussed.
PMID- 9644184
TI - [Effect of human recombinant gamma-interferon on proliferative activity of human
laryngeal cancer cell lines].
AB - The effect of human on PCNA expressions of HEP-2 lines was investigated using
LSAB (Labelled streptacidin biotin method) with monoclonal antibody Ki-67 (anti
PCNA). The results showed that the PCNA expression which reflects the
proliferative activity of cells was dependent on dose of rhu-IFN-gamma in HEP-2
cell lines. Thus, our data suggest that rhu-IFN-gamma might be useful in the
treatment of laryngeal cancer because it provides effective cytostatic.
PMID- 9644185
TI - [Study on the immune state of patients with laryngeal carcinoma].
AB - The authors have carried out the immunoassay on 68 patients with laryngeal
carcinoma in order to investigate the relationship between the occurrence and
development of the tumour and the body immune state by using the methods of R1D,
APAAP and LDH. The results showed that, in comparison with the normal group,
CD3+, CD4+ cell and NK cell activity were much lower (P < 0.01), CD8+ cell
slightly increased (P > 0.05). IgG, IgA and IgM were also lower (P < 0.05). It
indicates that the lower level of cellular immunity, the descent of the ratio of
CD4+/CD8+ and the condition which suppresses the body immune system are the
interior factors which make the laryngeal carcinoma happening and developing
easily. With the development of tumor, the increase of various suppressor factors
and the immune system suppressed further the tumor can spread and shift much more
easily.
PMID- 9644186
TI - [Suppressor gene p16 and head and neck tumors].
PMID- 9644187
TI - A creeping suspicion about radon.
PMID- 9644188
TI - Radio-free America: what to do with the waste.
PMID- 9644189
TI - Two steps forward on environmental justice.
PMID- 9644190
TI - Alternatives to Incineration: There's More Than One Way to Remediate.
PMID- 9644191
TI - Transgenic approaches for modifying the mammary gland to produce therapeutic
proteins.
AB - Bioengineering of the mammary gland to produce proteins of therapeutic and
industrial value is the result of extensive investigation of the physiology of
the mammary gland and the ability to generate transgenic animals. Targeting the
expression of heterologous proteins to mammary tissue requires a thorough
understanding of the biochemical events that coordinate growth and
differentiation of the mammary gland and of the hormonal and developmental
regulation of expression of milk protein genes. The characterization of mammary
specific promoter regions in milk protein genes and knowledge of the mechanisms
that confer integration site-independent expression of transgenes have
significantly contributed to modifying the mammary gland to produce heterologous
proteins of therapeutic interest. The generation of large transgenic farm animals
provides the opportunity for large-scale production of proteins in milk that have
a therapeutic value but are naturally present at low concentrations in biological
fluids. Transgenic mammary epithelial cells offer a versatile research model in
biomedical, environmental health, and neonatal toxicology research.
PMID- 9644192
TI - The cytochromes P450 and mechanisms of chemical carcinogenesis.
AB - This article reviews mechanisms of chemical carcinogenesis, from metabolic
activation and generation of reactive oxygen species by cytochromes P4511 and
P4502E to DNA damage, activation of protein kinase C and ocogenes, hyperplasia,
and proteoglycan changes in the cell glycocalyx and lysosomal enzymes which
mediate invasion and metastasis.
PMID- 9644193
TI - Health concepts, issues, and experience in the Abakaliki area, Nigeria.
AB - Environmental health problems are increasingly receiving global attention. The
health of entire nations may not only be affected by adverse environmental
conditions, but by nutritional deficiencies that lead to morbidity and mortality.
The type and extent of adverse health effects in a population depend on the
potential for exposure to some environmental factors and pathogens as well as
other environmental variables like industrialization, sanitation conditions, and
urbanization. National and international comparisons between health status
indicators can reveal the extent of any differences that exist, including dynamic
changes in prevailing environmental conditions which may be helpful in
characterizing the role of specific risk factors. Improvements in collection of
environmental data related to health can help to identify, control, and eliminate
many of the factors that are associated with environmental risk in the Abakaliki
area of eastern Nigeria.
PMID- 9644194
TI - Nitrite inhalants: history, epidemiology, and possible links to AIDS.
AB - Nitrite inhalants have been commonly abused substances in the United States.
Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause
of AIDS was not known. With the discovery of HIV, concern about nitrite use in
the USA waned. However, nitrite inhalant use is associated with behavioral
relapse and HIV transmission among gay men, with decreased lymphocyte counts and
natural killer cell activity in a few laboratory studies, and it remains a
candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma.
Discouraging nitrite use continues to be a worthwhile public health goal.
PMID- 9644195
TI - Characterization by scanning transmission electron microscopy of silica particles
from alveolar macrophages of coal miners.
AB - The structure and composition of silica-rich particles recovered by lavage from
the lungs of three active miners with different medical histories were studied
using high-resolution electron microscopy and chemical microanalysis. The results
are compared to the similarly determined structure and composition of respirable
size mineral particles obtained from roof-bolter dust-box samples from two coal
mines of widely different bulk quartz concentrations. The results show that the
lungs of the miners contain silica-based particles with structures not found in
the mine samples. Also, the particle structures and compositions found in the
macrophages were different in each of the miners. The results suggest that
possibility that intracellular processes may affect the susceptibility of
individuals to silica-induced pneumoconioses.
PMID- 9644196
TI - Environmental tobacco smoke is just as damaging to DNA as mainstream smoke.
AB - This study demonstrates the ability of tar isolated from environmental tobacco
smoke (ETS) to nick DNA in mammalian cells. Solutions of ETS tar behave similarly
to aqueous solutions of cigarette tar from mainstream smoke. Both solutions
contain the tar semiquinone radical, and this radical associates with the DNA in
viable rat alveolar macrophages. Solutions of tar from ETS cause single-strand
DNA breaks in rat thymocytes in proportion to the amount of tar present, until a
plateau is reached. ETS tar solutions, like mainstream tar solutions, produce
hydrogen peroxide. Hydrogen peroxide appears to be an essential component of the
mechanism by which both ETS tar and mainstream tar cause DNA damage in rat
thymocytes, as catalase substantially protects against DNA damage. Glutathione
also protects against DNA nicking by both ETS and mainstream tar solutions by
scavenging radicals and/or oxidants. The chelator diethylenetriamine pentaacetic
acid also provides partial (40%) protection. The studies demonstrate that the
water-soluble components of ETS tar can enter cells, associate with, and then
nick DNA.
PMID- 9644197
TI - Changes in serial blood lead levels during pregnancy.
AB - The first step in modeling lead kinetics during pregnancy includes a description
of sequential maternal blood lead (PbB) during pregnancy and the factors
controlling it. We analyzed PbB of 105 women living in the Valley of Mexico from
week 12 to week 36 of pregnancy and again at parturition. We also used data from
all women contributing blood at any stage of pregnancy to determine antecedents
of PbB. Pregnancies were uneventful, and offspring were normal. Although
geometric mean PbB level averaged around 7.0 micrograms/dl (0.34 mumol/l), with a
range of 1.0-35.5 micrograms/dl throughout pregnancy, analysis of variance
revealed a significant decrease in mean PbB from week 12 to week 20 (1.1
micrograms/dl) and various significant increases in mean PbB from week 20 to
parturition (1.6 micrograms/dl). Regression analyses confirmed the positive
linear PbB trend from 20 weeks to parturition and additional contributions of
dietary calcium, reproductive history, lifetime residence of Mexico City, coffee
drinking, and use of indigenous lead-glazed pottery. Although decreasing
hematocrit has been suggested to explain first-half pregnancy PbB decrease, the
time course of hematocrit decrease in the present study did not match the
sequential changes in PbB. While hemodilution and organ growth in the first half
of pregnancy may account for much of the PbB decrease seen between 12 and 20
weeks, the remaining hemodilution and accelerated organ growth of the last half
of pregnancy do not predict the trend toward increasing maternal PbB
concentration from 20 weeks to delivery. Mobilization of bone lead, increased gut
absorption, and increased retention of lead may explain part of the upward PbB
trend in the second half of pregnancy. Reduction of lifetime lead exposure may be
required to decrease risk of fetal exposure.
PMID- 9644201
TI - The manganese superoxide dismutase from the penicillin producer Penicillium
chrysogenum.
AB - The antioxidant enzyme superoxide dismutase has been studied in order to define
mechanisms for the influence of oxygen on penicillin production. Manganese
containing SOD activity was purified from penicillin-producing cultures of the
filamentous fungus Penicillium chrysogenum and reverse genetics was used to
identify full-length cDNA and genomic clones. Sequence analysis revealed a 630-bp
ORF containing three exons and two introns with fungal consensus splice-site
junctions. The deduced amino-acid sequence (210 amino acids; 23.13 kDa) includes
conserved residues required for enzymatic activity and metal binding, and shares
significant similarity with Mn- and Fe-containing superoxide dismutases. The sod
gene is present as a single copy in the genome of different P. chrysogenum
strains and its expression level is not correlated with penicillin-G
productivity.
PMID- 9644202
TI - Functional analysis of different regions of the positive-acting CYS3 regulatory
protein of Neurospora crassa.
AB - In the filamentous fungus Neurospora crassa during conditions of sulfur
limitation, CYS3, a major positive-acting regulatory protein, turns on the
expression of an entire set of genes which encode permeases and enzymes involved
in the acquisition of sulfur from environmental sources. CYS3 functions as a
homodimeric protein and possesses a b-Zip domain that confers sequence-specific
DNA binding. Expression of various hybrid GAL4-CYS3 fusion proteins in yeast was
used to detect regions involved in gene activation. An amino-terminal
serine/threonine-rich domain of CYS3 alone strongly activated expression of beta
galactosidase, the yeast reporter. Moreover, mutant CYS3 proteins with amino-acid
substitutions in this region that showed increased expression in Neurospora also
displayed an enhanced activation potential in yeast. The cys-3 gene of the exotic
N. crassa Mauriceville strain and of N. intermedia were cloned and demonstrated
to be functional for gene activation and for sulfur-mediated regulation by
complementation of a loss-of-function cys-3 mutation. The amino-terminal
serine/threonine-rich region is highly conserved in these two CYS3 proteins, in
agreement with the possibility that it serves as the activation domain.
Surprisingly, an extended promoter region of the cys-3 gene in the Mauriceville
strain and in N. intermedia was very well conserved with that of the standard N.
crassa gene, including the presence of three CYS3-binding sites possibly involved
in autogenous control. Results are presented which indicate that synthesis of the
CYS3 regulatory protein is highly regulated and can be detected in the nucleus of
cells subjected to sulfur de-repression, but is not found in the nucleus or the
cytoplasm of S-repressed cells. The amino-acid substitutions of the CYS3 protein
present in a temperature-sensitive cys-3 mutant and in a second-site revertant of
a cys-3 null mutation are presented and are shown to affect their DNA-binding
activities.
PMID- 9644203
TI - Functional analysis of upstream activating elements in the promoter of the FBP1
gene from Saccharomyces cerevisiae.
AB - We have investigated the effect of different carbon sources and of different
mutations on the capacity of two elements, UAS1 and UAS2, from the promoter of
the FBP1 gene to form specific DNA-protein complexes and to activate expression
of a reporter gene. The complexes are observed with nuclear extracts from yeast
derepressed on glycerol or ethanol. When hxk2 mutants are grown on glucose the
nuclear extracts are able to complex UAS1 but not UAS2, while for wild-type cells
grown on galactose only the complex with UAS2 is formed. In contrast, in vivo the
operation of both UASs is high in ethanol, moderate to low in glycerol, and
negligible in galactose; no expression is observed in glucose even in a hxk2
background. There is no effect of a MIG1 deletion, either in the formation of DNA
protein complexes or on the expression of reporter genes.
PMID- 9644204
TI - Isolation of UBP3, encoding a de-ubiquitinating enzyme, as a multicopy suppressor
of a heat-shock mutant strain of S. cerevisiae.
AB - Yeast strains lacking functional copies of the two genes SSA1 and SSA2, which
encode cytosolic molecular chaperones, are temperature-sensitive. In this report,
we describe the isolation of a high-copy suppressor of this temperature
sensitivity, UBP3, which encodes a de-ubiquitinating enzyme. We show that ubp3
mutant yeast strains have a mild slow-growth phenotype and accumulate ubiquitin
protein conjugates. We propose a model in which Ubp3p acts in vivo to reverse the
ubiquitination of substrate proteins, allowing temporarily misfolded proteins an
opportunity to fold correctly.
PMID- 9644205
TI - Editing status of mat-r transcripts in mitochondria from two plant species: C-to
U changes occur in putative functional RT and maturase domains.
AB - The intronic mat-r ORF encodes a protein with significant homology to retroviral
reverse transcriptases. Here, we describe the nucleotide sequence of potato mat-r
and study the editing status of mat-r transcripts in two systems, potato and
wheat, where the mat-r ORF is part of the trans-introns but in two different
configurations relative to nad1 exons d and e. In potato and wheat, 13 and 15 C
to-U transitions respectively were observed. Most transcripts were partially
edited, but potato transcripts were edited more efficiently than wheat
transcripts. As in functional mitochondrial genes, RNA editing increased the
similarity between plant mat-r proteins and their homologous non-plant
counterparts. Interestingly, editing of mat-r was clustered in the reverse
transcriptase (RT) and the maturase (X) domains, two well defined regions having
known functions in other systems. These results, together with the integrity and
sequence conservation of mat-r, strongly suggest that the encoded protein plays a
functional role in plant mitochondria.
PMID- 9644206
TI - Interaction of mitochondrial RNA editing and nucleolytic processing in the
restoration of male fertility in sorghum.
AB - Nucleolytic processing of transcripts within mitochondrial orf107, associated
with male sterility in sorghum, is regulated by the fertility restoration gene
Rf3, conferring 75% cleavage of whole-length transcripts. Two transcript editing
sites are 81% and 61% edited in rf3rf3 lines, while these sites are 41% and 10%
edited in the remaining whole-length transcripts in an Rf3Rf3 line. RNA editing
and processing efficiency in F1 progeny were similar to the Rf3Rf3 parent, and
analyses of backcross progeny indicated that all rf3rf3 lines were characterized
by high editing efficiency. We postulate that highly edited transcripts within
the population are quickly processed in lines carrying Rf3, generating a residual
population of poorly edited transcripts. Thus, action of Rf3 may have no direct
affect on RNA editing, and may be dependent on a substrate of highly edited
transcripts. These data indicate a potentially novel role of RNA editing in gene
expression through an influence on the efficiency of transcript processing.
PMID- 9644207
TI - Differential changes in copy numbers of rice mitochondrial plasmid-like DNAs and
main mitochondrial genomic DNAs that depend on temperature.
AB - The mitochondria of rice contain four kinds of circular plasmid-like DNAs,
namely, B1, B2, B3 and B4, in addition to the main mitochondrial genomic DNAs. In
order to examine the genetic stability of mitochondrial plasmid-like DNAs,
changes in the amounts of plasmid-like DNAs and main mitochondrial genomic DNAs
were analyzed in calli that had been cultured at various temperatures. The
observed effect of temperature on the levels of plasmid-like DNAs was larger than
that on the main mitochondrial genomic DNAs. A significant reduction in the copy
number of plasmid-like DNAs was detected in calli cultured at 35 degrees C, as
compared to 20 degrees C, 25 degrees C and 30 degrees C. The effect of
temperature on DNA synthesis in isolated mitochondria was also analyzed.
Synthesis of the main mitochondrial genomic DNAs occurred at all the temperatures
examined, whereas synthesis of plasmid-like DNAs occurred only over a limited
range of temperatures. The results of both in vivo and in vitro analyses suggest
that plasmid-like DNAs are less stably maintained than the main mitochondrial
genomic DNAs, which is consistent with the notion that the transmission of
mitochondrial plasmid-like DNAs from one generation to the next may be unstable
under unusual conditions.
PMID- 9644208
TI - Isolation of a Trichoderma reesei cDNA encoding GTP: a-D-mannose-1-phosphate
guanyltransferase involved in early steps of protein glycosylation.
AB - A cDNA coding for GTP: alpha-d-mannose-1-phosphate guanyltransferase (MPG1
transferase) (EC 2.7.7.13) was isolated from a cDNA library of the Trichoderma
reesei RutC-30 strain by suppression of the yeast Saccharomyces cerevisiae
mutation in the DPM1gene encoding mannosylphosphodolichol (MPD) synthase. The
nucleotide sequence of the 1.6 kb-long cDNA revealed an ORF which encodes a
protein of 364 amino acids. Sequence comparisons demonstrate 70% identity with
the S. cerevisiae guanyl transferase gene (MPG1) and 75% identity with the
Schizosaccharomyces pombe homologue. No similarity was found with the MPD
synthase encoded by the S. cerevisiae DPM1 gene. The possibility that cloned cDNA
encodes a product with a MPD synthase activity was also excluded by transforming
a heterozygous S. cerevisiae dpm1::LEU2/DPM1 diploid, which did not lead to the
restoration of viability of the dpm1 spores. Simultaneously, a significant
increase in MPG transferase activity, as compared with the wild-type yeast, was
observed in cellular extracts when the mpg1 cDNA from Trichoderma was expressed
in the S. cerevisiae dpm1-6 mutant.
PMID- 9644209
TI - Candida albicans ALS3 and insights into the nature of the ALS gene family.
AB - The ALS1 (agglutinin-like sequence) gene of Candida albicans encodes a protein
similar to alpha-agglutinin, a cell-surface adhesion glycoprotein of
Saccharomyces cerevisiae (Hoyer et al. 1995). A central domain of a tandemly
repeated 108-bp sequence is found in the ALS1 coding region. This tandem-repeat
motif hybridizes to multiple C. albicans genomic DNA fragments, indicating the
possibility of other ALS1-like genes in C. albicans (Hoyer et al. 1995). To
determine if these fragments constitute a gene family, tandem-repeat-hybridizing
genomic fragments were isolated from a fosmid library by PCR screening using
primers based on the consensus tandem-repeat sequence of ALS1 (Hoyer et al.
1995). One group of fosmids, designated ALS3, encodes a gene with 81% identity to
ALS1. The sequences of ALS1 and ALS3 are most conserved in the tandem-repeat
domain and in the region 5' of the tandem repeats. Northern-blot analysis using
unique probes from the 3' end of each gene demonstrated that ALS1 expression
varies, depending on which C. albicans strain is examined, and that ALS3 is
hyphal-specific. Both genes are found in a variety of C. albicans and C.
stellatoidea strains examined. The predicted Als1p and Als3p exhibit features
suggesting that both are cell-surface glycoproteins. Southern blots probed with
conserved sequences from the region 5' of the tandem repeats suggest that other
ALS-like sequences are present in the C. albicans genome and that the ALS family
may be larger than originally estimated.
PMID- 9644210
TI - Dihydropyridine receptor isoform expression in adult rat skeletal muscle.
AB - The expression of isoform-specific dihydropyridine receptor Ca2+ channel (DHPR)
alpha1-subunit genes in rat diaphragm, soleus and extensor digitorum longus
muscles was investigated using RNase protection assays. As expected, mRNA
expression levels for the DHPR skeletal muscle isoform were highest in extensor
digitorum longus. Unexpectedly, both diaphragm and soleus expressed mRNA for the
cardiac isoform at a significant level. Moreover, immunohistochemical experiments
provided evidence of the cardiac DHPR isoform at the protein level in muscle
fibres. The presence of the cardiac DHPR in the soleus and diaphragm is
consistent with a degree of reported cardiac-like excitation-contraction coupling
in these muscles, and may be an explanation for some of the therapeutic effects
of theophylline in asthmatics, but is likely to serve some other role(s) as well.
PMID- 9644211
TI - Involvement of deoxygenation-induced increase in tyrosine kinase activity in
sickle cell dehydration.
AB - Deoxygenation of sickle (SS) cells causes cationic alterations leading to cell
dehydration by various mechanisms, including activation of Ca2+-sensitive K
channels and possibly of K-Cl cotransport. Since an abnormal tyrosine kinase (TK)
activity exists in SS cells we investigated the possible role of tyrosine
phosphorylation in SS cell dehydration. In density-fractionated SS reticulocytes
and discocytes, but not in normal red cells, deoxygenation increased membrane and
cytosolic TK activities and tyrosine phosphorylation of band 3, independently of
external Ca2+. These effects were abolished by the TK inhibitors methyl 2, 5
dihydroxycinnamate (DiOH) or tyrphostin 47 (T47). Deoxygenation-induced Ca2+
uptake was not affected by the inhibitors and Na+ gain was reduced by T47 and not
by DiOH. Both inhibitors decreased the loss of K+ and cellular dehydration. The
effect of the inhibitors on K+ efflux was still observed in the absence of
external Ca2+. These data indicate that the TK inhibitors do not interfere with
deoxygenation-induced membrane permeabilization, but affect Ca2+-independent K+
efflux. It cannot be excluded, however, that the TK inhibitors also attenuate
Ca2+-sensitive K+ efflux. Based on recent evidence from the literature, it is
suggested that the diminution of K+ efflux results in part from inhibition of K
Cl cotransport activity.
PMID- 9644212
TI - Positive feedback regulation of angiotensin II-AT1B receptor gene expression in
rat adrenal glands.
AB - This study aimed to investigate the role of endogenous angiotensin II (ANGII) in
the upregulation of ANG-II AT1 receptors in adrenal glands during a low-salt
intake. To this end male Sprague-Dawley rats were fed a low-salt diet (0.2 mg/g)
for 10 days and were treated with the ANGII-AT1 receptor antagonist losartan (40
mg/kg per day) for 2 days, and adrenal mRNA levels for ANGII AT1A and AT1B
receptors were determined by RNase protection. The low-salt diet increased AT1A
and AT1B receptor mRNA levels by 90% and 220%, respectively. Losartan treatment
did not change the basal AT1A mRNA level, but decreased AT1B mRNA by 50%.
Treatment of rats on a low-salt diet with losartan did not change the increase of
AT1A mRNA but significantly attenuated the increase of AT1B mRNA to 90% of the
control value. Stimulation of endogenous ANGII levels by unilateral renal artery
clipping for 2 days lowered AT1A mRNA by 25% and increased AT1B mRNA by 30%.
Additional treatment with losartan did not affect the decreased AT1A mRNA levels
in rats with a unilateral renal artery clip, but significantly attenuated the
increase of AT1B mRNA. These findings suggest that sodium deficiency stimulates
adrenal AT1A and AT1B receptor mRNA levels primarily via an ANGII-AT1-independent
mechanism. The preferential increase of adrenal AT1B mRNA during a low-salt
intake could be explained by the elevation of endogenous ANGII levels during
sodium deficiency, suggesting that endogenous ANGII acts as an enhancer for
adrenal AT1B but not for AT1A receptor gene expression via ANGII-AT1 receptors.
PMID- 9644213
TI - Maitotoxin (MTX) activates a nonselective cation channel in Xenopus laevis
oocytes.
AB - Maitotoxin (MTX) may exert its toxic effect by activating ion conductances and
has been shown to elicit a fertilization-like response in Xenopus laevis oocytes.
In the present study we investigated the electrophysiological response of stage V
VI Xenopus oocytes to MTX using the two-microelectrode voltage-clamp technique.
Membrane voltage (Vm) measurements demonstrated that MTX (50 pM to 1 nM)
depolarized the oocytes from -49+/-7 to -14+/-1 mV. Subsequent replacement of
bath Na+ by the impermeant cation NMDG (N-methyl-d-glucamine) shifted Vm from
14+/-1 to -53+/-5 mV (n=29). This indicates that MTX activates a cation
conductance. Indeed, current measurements at a holding potential of -60 or -100
mV showed that within 10 s of MTX application an inward current component
developed which was largely abolished by extracellular Na+ removal. After a 1-min
application of 1 nM MTX the NMDG-sensitive current increased more than 100-fold
from 0.14+/-0.03 microA to a peak value of 21+/-3 microA (n=11). The effect of
MTX was concentration dependent with an EC50 of about 250 pM but only slowly
reversible. Ion substitution experiments indicated that the stimulated
conductance was nonselective for monovalent cations with a slight preference for
NH4+ (2.1) > K+ (1.5) > Na+ (1.0) > Li+ (0.7). Regarding divalent cations, a
complex biphasic response to extracellular Na+ replacement by Ca2+ was observed,
which suggests that the stimulated channels may have a small Ca2+ permeability
but that exposure to high extracellular Ca2+ enhances recovery from MTX
stimulation. No significant conductance for Mn2+ was observed. Application of 1
mM benzamil, 1 mM amiloride, or 100 microM 1-(beta-[3-(4-Methoxyphenyl)-propoxy]
4-methoxyphenethyl)-1H-imidazol e hydrochloride (SK&F 96365) reduced the MTX
stimulated inward current by 81%, 62%, or 65%, respectively. Gd3+ had an
inhibitory effect of 29% and 38% at concentrations of 10 microM or 100 microM,
respectively. Flufenamic acid, niflumic acid, (RS)-(3,4-dihydro-6, 7
dimethoxyisoquinoline-1-gamma1)-2-phenyl-N,N-di-[2-(2,3, 4-trimethoxyphenyl)
ethyl]-acetamide (LOE908), and 3', 5'-dichlorodiphenylamine-2-carboxylic acid
(DCDPC), known blockers of other nonselective cation channels, had no significant
effect. We conclude that MTX activates a nonselective cation conductance in
Xenopus oocytes. The underlying channels may be involved in changes in Vm that
occur during the early stages of fertilization.
PMID- 9644214
TI - Ruthenium red reduces the Ca2+ sensitivity of Ca2+ uptake into cardiac
sarcoplasmic reticulum.
AB - Ruthenium red inhibits mitochondrial Ca2+ uptake and is widely used as an
inhibitor of ryanodine-sensitive Ca2+ channels that function to release Ca2+ from
the sarcoplasmic reticulum (SR) of muscle cells. It also has effects on other
Ca2+ channels and ion transporters. To study the effects of ruthenium red on Ca2+
transport into the SR of cardiac muscle cells, fluorescence measurements of Ca2+
uptake into cardiac SR vesicles were made. Ruthenium red significantly decreased
the Ca2+ sensitivity of SR uptake in a dose-dependent manner at concentrations
ranging from 5 microM to 20 microM. There were no significant effects of
ruthenium red on the maximum velocity or the Hill coefficient of SR Ca2+ uptake.
PMID- 9644215
TI - Individual characteristics of human walking mechanics.
AB - Twenty-four subjects walked at different speeds (V) from 0.4 to 2.6 m s-1, while
motion and ground reaction forces were recorded in 3-D space. The total
mechanical energy of each body segment was computed as the sum of the
gravitational potential, translation and rotation kinetic energies. Energy
profiles reveal that there are inter-individual differences, particularly at
moderate and fast V. In some subjects, the energy excursions are less pronounced,
and tend to evolve out of phase at the lower limbs and trunk. As a consequence,
there is a better transfer of energy between the trunk and the leg segments,
resulting in smaller oscillations of the net energy of the whole body. There is a
threefold variation of the rate of increment of lnPu (the mass-specific mean
absolute power) with lnV across subjects. We show that this variability cannot be
simply explained on the basis of the different biomechanical characteristics of
the subjects, but that it depends on the different kinematic strategies. Subjects
differ in their ability to minimize energy oscillations of their body segments
and to transfer mechanical energy between the trunk and the limbs. Individual
characteristics of the mechanical energy expenditure were correlated with the
corresponding kinematic characteristics. The changes of the elevation angles of
the lower limb segments covary along a plane in all subjects. Plane orientation
(quantified by the direction cosine of the normal with the thigh axis, u3t) at
any V is not the same in all subjects, but correlates with the net power output:
smaller values of u3t tend to be associated with smaller values of Pu, and vice
versa.
PMID- 9644216
TI - Role of physiological HCO3-buffer on intracellular pH and histamine release in
rat peritoneal mast cells.
AB - The purpose of this study was to examine how intracellular pH (pHi) regulation
and histamine release are affected by HCO3- in rat peritoneal mast cells. The pHi
was measured using the pH-sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)
carboxyfluorescein (BCECF). We observed a pHi of 6.88+/-0.012 (n=24) in resting
mast cells exposed to a HEPES buffer (pH 7.4), but a sustained drop of 0.21 pH
units to 6.67+/-0.015 (n=23) when we exposed the mast cells to a HEPES/HCO3-
buffer equilibrated at all time with 5% CO2 (pH 7.4). This fall in pHi is
inhibited by the carbonic anhydrase inhibitor dichlorphenamide and is Na+
independent, indicating the involvement of Na+-independent Cl-/HCO3- exchange
activity. Furthermore removal of external Cl- in the presence but not in the
absence of HCO3- reversed the Cl-/HCO3- exchange and induced an alkaline load.
The recovery from this alkaline load was dependent on external Cl- but
independent of Na+. Both the alkalinization and the recovery were inhibited by
the anion transport inhibitor 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic
acid (DIDS). In addition, 36Cl- uptake measurements confirm the presence of a Cl
/HCO3- exchanger. Histamine release stimulated by antigen and compound 48/80 was
substantially reduced in the presence of HEPES/ HCO3- buffer (pHo 7.4, pHi 6.66).
Histamine release was increased, however, when pHi was clamped to 6.66 in HCO3-
free media (pHo 6.9). We conclude that: (1) Na+-independent Cl-/HCO3- exchange
determines steady-state pHi in rat peritoneal mast cells; and (2) the reduction
in histamine release observed in the presence of HCO3- is not due to its effect
on pHi per se, but rather on other changes in ion transport.
PMID- 9644217
TI - The cation selectivity of the sarcoball Ca2+ channel in frog muscle fibres.
AB - We have measured single-channel currents from sarcoplasmic reticulum (SR) blebs
(sarcoballs) of frog skeletal muscle fibres using conventional patch-clamp
electrodes with excised patches. With both the pipette and bath solutions
containing 50 mM Ca(gluconate)2 the slope conductance of the single channels was
39.2 pS for the most commonly seen state, with a reversal potential of -0.4 mV.
The cation selectivity of this channel was investigated by replacing the bathing
solution with either gluconate or HEPES salts of selected cations. The Goldman
permeability ratios, calculated from the reversal potentials, were found to be
P(Ca2+)/P(K+)=2.4, P(Ca2+)/ P(Na+)=2.7, P(Ca2+)/P(Tris+)=3.1, P(Ca2+)/P(Mg2+)=1.0
and P(Ca2+)/P(Ba2+)=1.1. Each value for the monovalent ions was found to be less
than the corresponding value reported for the SR ryanodine receptor channel from
skeletal and cardiac muscle. Single-channel activity could be recorded when the
preparation was bathed in symmetrical 50 mM Mg(gluconate)2 solutions, and these
channels had a similar conductance and open probability to that measured when the
preparation was bathed in symmetrical Ca(gluconate)2 solution. The channel
activity in symmetrical 50 mM Ca(gluconate)2 solution was insensitive to bath
applied caffeine (5 mM) and ryanodine (10 microM). The results are in agreement
with the conclusion that the sarcoball Ca2+ channel is not the ryanodine receptor
release channel, but possibly a form of the SR Ca2+-ATPase which is uncoupled
from the catalytic events of the pump and acts as a passive ion channel.
PMID- 9644218
TI - The rise of nuclear and cytosolic Ca2+ can be uncoupled in HeLa cells.
AB - It has long been assumed that ionized Ca2+ is transmitted from the cytosol to the
cell nucleus through the nuclear pore complexes to trigger many nuclear functions
such as gene transcription after agonist stimulation. However, this hypothesis
has been challenged recently. In the present study, we have investigated the
interplay of Ca2+ in the cytosol and nucleus of HeLa cells upon histamine
stimulation by using confocal microscopy. In resting cells, addition of histamine
(50 microM) produced synchronous Ca2+ signals in the cytosol and nucleus with a
stronger fluo-3 emission in the nucleus. Our results also demonstrate that the
rise of cytosolic and nuclear free Ca2+ can be uncoupled after histamine
stimulation. This assertion is supported by the following observations: (1) when
heparin was injected into the cytosol, the increase in fluo-3 fluorescence in the
cytosol mediated by histamine was almost eliminated while that in the nucleus
still occurred; (2) when heparin was in the nucleus, the increase in the free
nucleoplasmic Ca2+ concentration ([Ca2+]n) elicited by histamine was abolished
while the rise of cytosolic Ca2+ level ([Ca2+]c) was seen; (3) when we injected
inositol 1,4,5-trisphosphate (IP3) directly into the nucleus, [Ca2+]n increased;
and (4) in the cells given cytosolic injections of BAPTA-dextran (70 kDa),
histamine evoked additional Ca2+ transients in the nucleus. These results suggest
that the nucleus of the HeLa cell has its own IP3-sensitive Ca2+ store and that
the Ca2+ signals in the nucleus and cytosol can be uncoupled.
PMID- 9644219
TI - Cellular taurine release triggered by stimulation of the Fas(CD95) receptor in
Jurkat lymphocytes.
AB - One of the hallmarks of apoptosis is cell shrinkage which appears to be important
for cell death. The mechanisms mediating cell volume decrease have, however, not
been addressed. Mechanisms employed by swollen cells to decrease their cell
volume include activation of ion transport pathways, such as ion channels and KCl
cotransport, and release of cellular osmolytes, such as taurine, sorbitol,
betaine and inositol. The present study has been performed to test for release of
taurine. To this end Jurkat human T-lymphocytes were loaded with [3H]taurine and
apoptotic cell death induced by triggering the Fas(CD95) receptor with monoclonal
crosslinking antibody. Triggering the Fas(CD95) receptor led to a release of 60+/
5% of cellular taurine within 90 min. The release did not occur prior to 45 min.
The release coincided with cell shrinkage as evidenced from forward scatter in
FACS analysis and preceeded DNA fragmentation according to propidium iodide
staining. The delay of taurine release was not influenced by exchange of medium
and thus was not due to extracellular accumulation of a stimulator. The Fas(CD95)
induced taurine release, cell shrinkage and DNA fragmentation were blunted by
lowering of ambient temperature to 23 degreesC. Following pretreatment of cells
with Fas(CD95) antibody at 23 degreesC rewarming led to rapid taurine release,
cell shrinkage and DNA fragmentation, indicating that the temperature-sensitive
step is distal to the mechanisms accounting for the delay. Osmotic cell swelling
led to an immediate release of taurine. In conclusion, Fas(CD95) triggering leads
to delayed taurine release through a temperature-sensitive mechanism.
PMID- 9644220
TI - Characteristics of L-alanine transport in cardiac sarcolemmal vesicles and into
isolated cardiac myocytes.
AB - During cardiac insults, heart cells synthesise and accumulate alanine as a part
of the anaerobic energy production pathway. The transport of alanine presumably
influences this pathway, making it important to characterise the L-alanine
transporter in the heart. In this study, we have investigated the transport of L
alanine across the sarcolemma using a novel approach, namely utilisation of two
preparations: cardiac sarcolemmal vesicles and cardiac myocytes. Both
preparations were isolated from the heart of the same mammalian species. L
Alanine uptake in both preparations was sodium dependent. In the sarcolemmal
vesicles, the sodium dependent component was electrogenic and saturated with an
estimated Michaelis-Menten constant (Km) and maximal reaction velocity (Vmax) of
0.48+/-0.18 mM and 279.97+/-64.17 pmol/mg per min respectively at room
temperature. In the isolated myocytes, L-alanine uptake was linear in sodium
containing media, with an estimated Km and Vmax of 9.65+/-0. 76 mM and 169.81+/
13.22 pmol/ microl per min respectively at 10 degreesC for the sodium-dependent
component. Inhibition of cotransport by a variety of substrates indicated that L
alanine uptake in the heart is mediated by an A- or ASC-like system. These
characteristics of L-alanine transport suggest that under ischaemic conditions, L
alanine efflux will be activated, thus allowing for the continuous utilisation of
other amino acids for energy production.
PMID- 9644221
TI - Skeletal muscle adaptations to prolonged training, overtraining and detraining in
horses.
AB - Thirteen standard-bred horses were trained intensively for 34 weeks and detrained
for 6 weeks to study skeletal muscle adaptations to prolonged training,
overtraining and detraining. Training included endurance (phase 1, 7 weeks), high
intensity (phase 2, 9 weeks) and overload training (OLT) (phase 3, 18 weeks).
During phase 3, horses were divided into two groups, OLT and control (C), with
OLT horses performing greater intensities and durations of exercise than C
horses. Overtraining was evident in OLT horses after week 31 and was defined as a
significant reduction in treadmill run time in response to a standardised
exercise test (P<0.05). Relationships between peripheral (skeletal muscle) and
whole body (maximum O2 uptake, V.O2, max, treadmill run time) adaptations to
training were determined. Prolonged training resulted in significant adaptations
in morphological characteristics of skeletal muscle but the adaptations were
limited and largely completed by 16 weeks of training. Fibre area increased in
all fibres while the number of capillaries per fibre increased and the
diffusional index (area per capillary) decreased. Mitochondrial volume density
continued to increase throughout 34 weeks of training and paralleled increases in
V.O2,max and treadmill run time. Significant correlations were noted between
mitochondrial volume and V.O2,max (R=0.71), run time and V.O2,max (R=0.83) and
mitochondrial volume and run time (R=0.57). We conclude that many of adaptive
responses of muscle fibre area and capillarity occur in the initial training
period but that markers of oxidative capacity of muscle indicate progressive
increases in aerobic capacity with increases in training load. The lack of
differences between C and OLT groups indicated that there may be an upper limit
to the ability of training stimulus to evoke skeletal muscle adaptive responses.
There was no effect of overtraining or detraining on any of the adaptive
responses measured.
PMID- 9644222
TI - Replacement of troponin-I in slow-twitch skeletal muscle alters the effects of
the calcium sensitizer EMD 53998.
AB - We extracted troponin-I (TnI) from skinned rat and rabbit soleus muscle fibres
using a modification of the method described by Strauss et al. (FEBS Lett 310:229
234, 1992) for replacement of TnI in cardiac preparations. Incubation of soleus
muscle fibres with 10 mmol/l vanadate virtually completely abolished the
Ca2+dependence of force. Immunoblot analysis revealed that more than 80% of TnI
had been extracted from the preparations. The Ca2+dependence of force was
restored by incubation with a complex of cardiac TnI (cTnI) and troponin-C
(cTnC). We examined the effects of the Ca2+-sensitizing compound EMD 53998 on
isometric tension in native porcine cardiac and rabbit soleus skinned fibres as
well as soleus in which the endogenous slow skeletal TnI (ssTnI) had been
replaced by cTnI (soleus-cTnI). It was found that 10 micromol/l EMD 53998 in
native soleus increased maximum Ca2+-activated force to 120+/-1.4% of control. In
soleus-cTnI fibres, maximum force was increased to only 105+/-0.9%, which was
similar to the effect observed in cardiac muscle (108+/-0.6%). In cardiac muscle,
10 micromol/l EMD 53998 induced a leftward shift of the pCa-tension relation by
0.65 log units. In native soleus, DeltapCa was only 0.40. Again, the effect of
EMD 53998 on soleus-cTnI (DeltapCa=0.56) more closely resembled the response
found in cardiac muscle than that observed in native soleus muscle. The apparent
TnI-isoform dependence of the effects elicited by EMD 53998 suggests that its
actions are modulated by the regulatory proteins of the thin filament.
PMID- 9644223
TI - 3,5-Diiodo-L-thyronine and 3,5,3'-triiodo-L-thyronine both improve the cold
tolerance of hypothyroid rats, but possibly via different mechanisms.
AB - The effects of 3,5-diiodo-L-thyronine (3,5-T2, 2.5-10 microg/100 g BW) on cold
tolerance, energy expenditure and oxidative capacity of four metabolically very
active tissues (brown adipose tissue, skeletal muscle, liver and heart) were
determined in hypothyroid, cold-exposed rats. Hypothyroid rats survived cold for
only 3-4 days. 3,5-T2 improved survival dose dependently; with 10 microg/100 g BW
the rats survived 3 weeks (limit of observation). This effect was paralleled by
an increased energy expenditure of the whole animal for the entire 3 weeks.
Similar effects were observed in hypothyroid rats treated with 3,3',5-triiodo-L
thyronine (T3). 3,5-T2 stimulated the specific oxidative capacity (expressed as
cytochrome oxidase activity per milligram protein) of all four tissues dose
dependently. When the oxidative capacity was expressed as total activity
(cytochrome oxidase activity times organ weight), the percentage increases were
of the same order. T3 exerted similar effects, but the changes in total activity
were much greater than in specific activity, indicating an effect on the tissue
trophism. The effect of 3,5-T2 on cold tolerance thus mimics the effect of T3,
but via different cellular mechanisms. T3 seems to act primarily on the trophism
of the tissues, while 3,5-T2 may act directly on mitochondria without an effect
on tissue trophism.
PMID- 9644224
TI - Hypotonicity stimulates translocation of ICln in neonatal rat cardiac myocytes.
AB - Cell volume expansion stimulates the efflux of solutes, including the amino acid
taurine, to accomplish a regulatory volume decrease (RVD). One protein that may
play a role in taurine efflux is the cytosolic protein ICln. In rat neonatal
cardiac myocytes under isotonic conditions, ICln is found predominantly (greater
than 90%) in the cytosol. However, after cell volume expansion by exposure to
hypotonic medium, ICln rapidly translocates to the particulate fraction (the
Triton X-114-insoluble fraction). After 2 min in hypotonic medium the percentage
of ICln in the particulate fraction increases to 30%, 46% at 5 min, 40% at 10
min, and 25% at 30 min. The time course of this response is similar to that of
hypotonicity-stimulated taurine efflux. Hypotonicity-stimulated taurine efflux as
well as ICln translocation parallel the reduction in medium osmolarity. As
osmolarity decreases, taurine efflux and ICln movement increase. The movement of
ICln from the particulate back to the cytosolic fraction is accelerated when
volume-expanded cells are returned to isotonic medium. When ICln is analyzed
under non-denaturing conditions, a dimer is detected in the particulate fraction
of volume-expanded cells, along with the monomer. This dimer is not detected in
the cytosol. Treatment of the particulate fraction from volume-expanded cells
with the lyotropic agent KSCN caused release of ICln but not Na-K-ATPase into the
soluble fraction, indicating that translocated ICln associates with membranes in
the particulate fraction rather than inserting into them.
PMID- 9644225
TI - Basolateral transport of glutarate in proximal S2 segments of rabbit kidney:
kinetics of the uptake process and effect of activators of protein kinase A and
C.
AB - The kinetics of tubular glutarate uptake, the coupling of glutarate to p
aminohippurate (PAH) transport and the effect of activators of protein kinase A
and C on glutarate uptake were studied using isolated S2 segments of proximal
tubules microdissected from rabbit kidneys without the use of enzymatic agents.
Because the tubules were not perfused, and hence were collapsed, the tubular
uptake of [14C]glutarate reflects transport across the basolateral cell membrane.
To obtain uptake rates most closely related to initial transport rates, 30 s
glutarate uptake measurements were performed. In a first set of experiments it
could be shown that preloading proximal S2 segments with glutarate (10(-3 )M)
stimulated [3H]PAH uptake indicating that glutarate may be a substrate of the PAH
/dicarboxylate exchanger. The kinetic data revealed a Km value of 0. 62 mM and a
Vmax value of 84.1 pmol nl-1min-1 for tubular [14C]glutarate uptake across the
basolateral cell membrane. In contrast to basolateral PAH transport (previous
studies from this laboratory), tubular 30 s [14C]glutarate uptake was not
affected by either the phorbol ester phorbol 12-myristate 13-acetate (PMA, 10(-7
)M), an activator of protein kinase C, or by the membrane-permeant analogues of
cAMP, dibutyryl cyclic AMP (db-cAMP, 10(-4 )M) and 8-bromoadenosine 3',5'-cyclic
monophosphate (Br-cAMP, 10(-4 )M). The results indicate that the protein kinases
A and C have no function in the regulation of the renal basolateral dicarboxylate
transporter. This finding agrees well with the structural feature of the recently
cloned rabbit renal dicarboxylate transporter which does not contain any putative
phosphorylation sites for protein kinase C or cAMP-dependent kinase.
PMID- 9644226
TI - A hyperpolarization-activated cation current (Ih) contributes to resting membrane
potential in rat superior cervical sympathetic neurones.
AB - Using perforated-patch voltage-clamp recording, a prominent hyperpolarization
activated inward cation current (Ih) has been identified in dissociated, cultured
and replated, superior cervical sympathetic (SCG) neurones from 17-day-old rats.
Ih was identified as a slowly activated inward current on hyperpolarizing from
60 mV, with an extrapolated null potential (in 3 mM [K+]out) of -42 mV. The
activation range for Ih was -40 to -100 mV, with a half-activation voltage (V0.5)
of -63 mV. The current was suppressed by 1 mM Cs+ but not by 1 mM Ba2+. The
reversal potential for the current change induced by Cs+ agreed with the null
potential for Ih. Ih conferred strong inward rectification to the current-voltage
curve negative to -55 mV in both voltage-clamp and current-clamp recording. This
inward rectification was reduced by 1 mM Cs+. In a sample of eight cells with
initial resting membrane potentials between -51 and -64 mV, Cs+ increased the
resting potential of all cells by between 2.5 and 21 mV. These results indicate
that Ih contributes a tonic inward (depolarizing) component to the maintenance of
the resting membrane potential in SCG neurones.
PMID- 9644227
TI - Sarcoplasmic reticulum Ca2+ loading in rabbits 8 and 15 weeks after coronary
artery ligation.
AB - Calcium uptake by cardiac sarcoplasmic reticulum (SR) is reported to be reduced
in heart failure in the human and in a number of animal models. However, the
majority of studies have examined end-stage heart failure in the human and few
animal studies have taken account of the duration and severity of left
ventricular dysfunction. In this study we have compared SR Ca2+ loading in a
haemodynamically assessed, coronary artery ligation model of heart failure at 8
and 15 weeks after ligation. Trabeculae were isolated from the right ventricle
and mounted for isometric tension measurement. They were treated with saponin to
permeabilize the sarcolemma but retain SR function and bathed in a mock
intracellular solution including adenosine triphosphate (ATP) and buffered Ca2+.
Caffeine was used to release Ca2+ from the SR. The amplitude of the caffeine
induced contracture was used as a quantitative gauge of the Ca2+ content of the
SR. Eight weeks after ligation, trabeculae demonstrated enhanced SR Ca2+ uptake
as manifest by larger caffeine-induced contractures (e.g. 200 nM [Ca2+], 120 s
loading - 38.2+/-9.2 versus 67.3+/-10.1% of maximum Ca2+-activated force, FCa,
max, P=0.03). At 15 weeks, trabeculae from ligated hearts were not significantly
different from controls with SR Ca2+ loading returning to control levels (e.g.
200 nM [Ca2+], 120 s loading - 47.3+/-9.6 versus 30.2+/-12.8% FCa, max, P=0.12).
These data suggest that SR Ca2+ loading may increase in the early stages of heart
failure and fall back to normal with an increasing duration of left ventricular
dysfunction. Increased incidence of spontaneous Ca2+ release observed from the SR
at 8 weeks and not at 15 weeks may represent an arrhythmogenic mechanism specific
to the early phase of heart failure.
PMID- 9644228
TI - Developmental and species differences in the response of the ureter to metabolic
inhibition.
AB - The effect of inhibiting oxidative phosphorylation on electrically stimulated
phasic and high-K+ depolarization-induced tonic contractions in ureteric smooth
muscle has been investigated. Intracellular [Ca2+] and pH were monitored
fluorimetrically with simultaneous tension measurement, in adult and neonatal rat
and guinea-pig ureter. Little difference was found in the response of adult or
neonatal rat ureters; cyanide abolished phasic contractions and intracellular
Ca2+ transients. The contractions of the adult guinea-pig ureter were also
reduced by cyanide, but not as much as those of the adult rat. Neonatal guinea
pig was, however, remarkably resistant to the effects of cyanide, with force and
Ca2+ transients remaining at control levels after an initial transient dip. These
differences between tissues were not apparent when a high K+ concentration was
used to depolarize tissues and produce maintained [Ca2+]i and force changes;
cyanide reduced force but not [Ca2+]i in all preparations. Intracellular pH
decreased in all preparations with inhibition of oxidative phosphorylation, but
this did not correlate with changes in contraction. It is concluded that there
are both species and developmental differences in the response to metabolic
inhibition of the ureter which lead to differing changes in contractile activity.
PMID- 9644229
TI - The effect of beta-blockade on plasma potassium concentrations and muscle
excitability following static exercise.
AB - The effects of beta-blockade on plasma [K+], muscle excitability and force during
fatiguing exercise were examined. Nine healthy males (mean age 22.3+/-1.7 yr)
performed a 3-min fatigue protocol that consisted of a sustained submaximal
contraction (30% of the maximal voluntary contraction, MVC) of the right
quadriceps muscle. Subjects performed the exercise after treatment with either
placebo, beta1-selective (metoprolol, 100 mg) or an equipotent dose of non
selective beta1,2-blockade (propranolol, 80 mg, n=6; 100 mg, n=2; 120 mg, n=1)
twice daily for 3 days before testing according to a randomized double-blind
design. Brachial arterial and femoral venous blood samples were drawn before,
during, and for 15 min following the contraction, together with maximal
stimulation of the right femoral nerve to evoke a twitch and a compound muscle
action potential (M-wave); the M-wave amplitude being used as an index of
sarcolemmal excitability. The exercise-induced rise in plasma [K+] did not differ
between treatments, but K+ re-uptake during recovery was slower following
propranolol. The recovery of the twitch was significantly related to the recovery
of plasma [K+] in all trials, but the evoked M-waves were unaffected by either
the contraction or the drug treatment. Propranolol resulted in a significantly
(P<0.05) greater reduction (51.9+/-7.3%) in MVC following the 3-min contraction
compared with metoprolol (40.7+/-3.6%) or placebo (38. 9+/-3.6%). These results
suggest that while beta1,2-blockade may significantly affect the recovery of
muscle force and K+ homeostasis after fatiguing exercise (presumably through an
inhibition of the Na+,K+-ATPase), it does not appear to affect surface membrane
excitability.
PMID- 9644230
TI - Estimation of outward currents in isolated human atrial myocytes using
inactivation time course analysis.
AB - The aim was to investigate outward currents in single, isolated, human, atrial
myocytes and to determine the relative contribution of individual current
components to the total outward current. Currents were recorded using the whole
cell patch-clamp technique at 36-37 degreesC. Individual outward current
components were estimated from recordings of total outward current using a
mathematical procedure based on the inactivation time course of the respective
currents. This method allows estimation of outward currents without the use of
drugs or conditioning voltage-clamp protocols to suppress individual current
components. A rapidly activating and partially inactivating total outward current
was recorded when myocytes were voltage clamped at potentials positive to -20 mV
(peak current density 24. 0+/-0.97 pA/pF at +40 mV; n=107 cells, 33 patients).
This total outward current comprised three overlapping currents: a rapidly
inactivating, transient, outward current (Ito1) a slowly and partially
inactivating current (ultrarapid delayed rectifier, IKur) and a third current
component which most probably reflects a non selective cation current (not
characterized). The average current densities at +40 mV were 8.92+/-0.44 pA/pF
for Ito1 and 15.1+/-0.72 pA/pF for IKur (n=107 cells). Recovery from inactivation
was bi-exponential for both currents and was faster for Ito1. A slowly activating
delayed rectifier current (IK) was not found. The current densities of peak Ito1
and IKur varied strongly between individual myocytes, even in those from the same
patient. The ratio IKur/Ito1 was 0.5-6.9 with a mean of 1.98+/-0.11 (n=107
cells), suggesting that IKur is the main repolarizing current. The amplitudes of
the total outward current, Ito1 and IKur, and the ratio of the latter two were
independent of patient age (16-87 years).
PMID- 9644231
TI - Influence of substrate structure on turnover of the organic cation/H+ exchanger
of the renal luminal membrane.
AB - We examined the influence of organic cation (OC) structure on the rate of
turnover of the OC/H+ exchanger in rabbit renal brush-border membrane vesicles
(BBMV). The rate of efflux of [14C]tetraethylammonium ([14C]TEA) from BBMV,
measured in the presence of an inwardly directed chemical gradient for test
agent, provided an indirect measure of activity of the OC/H+(OC) exchanger. The
trans-stimulation of [14C]TEA efflux from BBMV was a saturable function of
increasing extravesicular concentration of both unlabeled TEA and
tetramethylammonium (TMA), with an apparent Michaelis constant (Kt) for the
interaction of these compounds with the OC/H+(OC) exchanger of 25 microM and 1
mM, respectively. The effect on [14C]TEA efflux of saturating extravesicular
concentrations of a series of n-tetraalkylammonium compounds was examined.
Whereas the short-chain compounds TMA and TEA markedly stimulated [14C]TEA efflux
(by 830% and 690%, respectively), the long-chain compounds tetrapropylammonium
and tetrabutylammonium were less effective, increasing efflux by only 40% and
120%, respectively. When the exchanger was saturated with tetrapentylammonium,
mediated efflux of [14C]TEA was reduced. Increasing alkyl chain length was also
correlated with an increase in the inhibitory effect (as measured by the apparent
inhibition constant, Ki, or the IC50 value) that these compounds had against
transport of [14C]TEA by the OC/H+(OC) exchanger; i.e., there was a correlation
between decreasing IC50 and decreasing turnover of the OC/H+(OC) exchanger. This
same correlation was observed for a broader set of test agents of diverse
molecular structure, including a series of n-tetraalkylammonium and -phosphonium
compounds and the OCs, choline, N1-methyl nicotinamide, 1-methyl-4
phenylpyridinium, and amiloride. Because high affinity of substrates for the
OC/H+(OC) exchanger is correlated with increasing substrate hydrophobicity, we
conclude that the interaction of hydrophobic OCs with the renal OC/H+(OC)
exchanger results in the formation of a substrate-exchanger complex that has a
comparatively low rate of turnover.
PMID- 9644232
TI - Endosomes: another extra-mitochondrial location of type-1 porin/voltage-dependent
anion-selective channels.
AB - Endocytotic vesicles (EV) isolated from rat renal cortex were subjected to SDS
polyacrylamide gel electrophoresis and Western blotting. A monoclonal antibody
against human type-1 porin (31 kDa) detected a strong band of 31 kDa. The same
antibody has been used as the primary antibody in indirect immunocytochemistry.
Light microscopy of cryostat sections of rat renal cortex showed a heavy staining
of EV underneath the brush-border membrane. Electron microscopy was performed by
"preembedding immunogold staining" of rat renal cortex, the sections of which
showed an extensive labelling of EV with gold particles. These results
demonstrate that the expression of type-1 porin is not restricted to outer
mitochondrial membranes. The biological function of endosomal type-1 porin has as
yet to be ascertained.
PMID- 9644233
TI - Transport-mediated release of endogenous glutamate in the vertebrate retina.
AB - In the present study we measured calcium-dependent, vesicular glutamate release,
and calcium-independent, transport-mediated glutamate release patterns in the
vertebrate retina to better understand the sources of elevated glutamate in
neural tissue under ischemic conditions. A potassium concentration of 40 mM,
which mimics the extracellular potassium concentration in the central nervous
system during ischemia, was applied to the bathing medium of a retinal slice
prepared from zebrafish. High external potassium evoked release of endogenous
glutamate that was measured using a glutamate-specific fluorometric assay applied
to the bath. The slice was visualized under 668 nm light using Normarski optics
and fluorescent images were captured using a cooled charge-coupled device (CCD)
camera. Following the elevation of external potassium to 40 mM several bands of
glutamate fluorescence, reflecting the spatial distribution of glutamate release,
were observed. A calcium-dependent cloud of glutamate was observed in the inner
plexiform layer, that was antagonized by bath-applied nifedipine. A relatively
dense glutamate cloud (1-10 microM) was observed over the ganglion cell layer,
which was blocked by dihydrokainate, a glutamate transport antagonist. In
contrast, nifedipine, an inhibitor of calcium-dependent neurotransmitter release
in the retina, failed to block the cloud of released glutamate in the ganglion
cell layer. These data suggest that under pathological conditions in the eye
where glutamate levels are elevated surrounding retinal ganglion cells, such as
observed in some forms of glaucoma, a possible source of the elevated glutamate
is through a glutamate transporter operating in a reversed direction. A likely
candidate for mediating this reversed transport of glutamate is the retinal
Muller cell.
PMID- 9644234
TI - Single-channel properties of the sarcoplasmic reticulum calcium-release channel
in slow- and fast-twitch muscles of Rhesus monkeys.
AB - RyR1 is the main isoform of ryanodine receptor expressed in fast- and slow-twitch
mammalian skeletal muscles although differences in Ca2+-release kinetics and
properties have been reported. Single-channel measurements reveal that a large
proportion (82%) of Ca2+-release channels measured in slow-twitch muscle
preparations have properties similar to those of the Ca2+-release channels of
fast-twitch preparations, i.e. the same conductance, an identical sensitivity to
caffeine and a bell-shaped Ca2+ activation curve for pCa (-log10[Ca2+]) 7 to 3. A
low proportion (18%) of Ca2+-release channels observed in preparations from slow
twitch muscles were characterized by a very high activity level. These channels
were not inhibited at a millimolar concentration of Ca2+. Our data suggest that
the different properties of Ca2+ release in slow- and fast-twitch muscles might
not be related to intrinsic properties of the Ca2+-release channels of each type
of muscle but rather to the co-expression of two isoforms of ryanodine receptor
and the lower amount of Ca2+-release channels expressed in slow- than in fast
twitch muscles.
PMID- 9644235
TI - Real-time measurements of calcium dynamics in neurons developing in situ within
zebrafish embryos.
AB - We have developed a non-invasive technique to measure intracellular calcium
([Ca2+]i) in neurons growing within intact embryos of the zebrafish (Danio
rerio). A single blastomere was injected with a calcium-sensitive fluorescent dye
(Calcium Green dextran) between the 32- and 128-cell stage and the embryo imaged
between 16 h and 20 h postfertilisation using laser scanning confocal microscopy.
Labelled nerve cells from embryos preinjected with dye and dissociated at 16 h
showed a fluorescence increase (66+/-22%; n=11) in response to depolarisation
with KCl confirming that the dye remained intracellular and was sensitive to
calcium. In addition, fluorescence changes in activated muscle cells of intact
embryos showed that the dye was capable of responding to [Ca2+]i changes in vivo.
Imaging of dye loaded cells over 30-min periods in embryos between 16 and 20 h
revealed that the majority of neurons within the brain and spinal cord did not
show spontaneous fluorescence changes distinguishable from noise. However, a
subset of neurons within the ventral spinal cord exhibited spontaneous,
repetitive [Ca2+]i oscillations which may have a functional significance during
neuronal development.
PMID- 9644236
TI - Suppression of the carbachol-activated nonselective cationic current by antibody
against alpha subunit of Go protein in guinea-pig gastric myocytes.
AB - In this study, we investigated which subtype of GTP-binding protein (G protein)
is related to muscarinic activation of nonselective cation (NSC) channels in
gastric smooth muscle. Inward cationic current was activated by the application
of 50 microM carbachol (ICCh) at a holding potential of -60 mV with the same CsCl
rich solution in both pipette and bath. The same cationic current as ICCh was
slowly activated by the dialysis of guanosine 5'-O-(3-thiotriphosphate)
(GTP[gamma-S]) through the pipette. Since it is known that pertussis toxin
pretreatment can block ICCh, antibodies (Abs) against Galpha,i (anti-Galpha,i) or
Galpha,o (anti-Galpha,o) were tested. Activation of ICCh was blocked by the
addition of anti-Galpha,o. However, anti-Galpha,i Abs had no significant effect
on ICCh. The expression of Galpha,o in guinea-pig gastric smooth muscle was
confirmed by Western immunoblot analysis. These results suggest that Go-type
protein may mediate signals from the muscarinic receptor to NSC channel in guinea
pig gastric myocytes.
PMID- 9644237
TI - Downstream of phosphatidylinositol-3 kinase, a multifunctional signaling
molecule, and its regulation in cell responses.
AB - Phosphatidylinositol (PI)-3 kinase is an enzyme that phosphorylates the D-3
position of PI and its derivatives. It is activated immediately after growth
factor or differentiation factor stimulation, suggesting that PI-3 kinase is
involved in signal transduction of the stimulation. PI-3 kinase appears to play
various important roles including signaling to the nucleus, vesicle transport,
and rearrangement of the cytoskeleton since many cell responses which require
these events are affected by inhibition or activation of PI-3 kinase. To
understand how PI-3 kinase can act in such multiple ways, it is important to
identify the factors downstream of PI-3 kinase. In this review, we discuss the
factors downstream of PI-3 kinase and the methods used to identify them. Recent
studies revealed that some proteins involved in vesicle transport or in
rearrangement of the cytoskeleton are regulated by the phospholipids generated by
PI-3 kinase, implying the mechanism by which PI-3 kinase regulates these cell
responses.
PMID- 9644238
TI - Induced mouse models of abnormal sphingolipid metabolism.
AB - Only a limited number of genetic mouse models of abnormal sphingolipid metabolism
are known to occur spontaneously. However, recent progress in the combined
homologous recombination and embryonic stem cell technology allows inactivation
of any genes of choice once they are cloned. Not only is it possible to generate
mutant mouse lines that are equivalent to known human genetic disorders but
genetic conditions unknown or highly unlikely to occur in humans, such as
simultaneous inactivation of more than one gene, can also be created. Most of the
human disorders due to genetic defects in sphingolipid catabolism have been
duplicated in the mouse. With increasing activity in cloning of the enzymes
involved in sphingolipid biosynthesis, genetic mouse models of abnormal
sphingolipid biosynthesis are beginning to appear. These models have already
provided invaluable insight into the metabolism and physiological functions of
sphingolipids and are expected to be utilized extensively for evaluation of the
pathogenesis and of treatment approaches of these genetic disorders.
PMID- 9644239
TI - X-ray structure of a reaction intermediate of L-2-haloacid dehalogenase with L-2
chloropropionamide.
AB - The crystal structure of a complex prepared by soaking a single crystal of the
S175A mutant of L-2-haloacid dehalogenase from Pseudomonas sp. YL in a solution
containing a poor substrate, L-2-chloropropionamide, has been determined by X-ray
analysis at 2. 15 A resolution with a crystallographic R factor of 19.8%. The
present analysis has revealed the structure of the reaction intermediate trapped
in the crystal. In the intermediate, the substrate moiety lacking chlorine is
covalently bound to the carboxyl group of D10, and adopts the pro-D-configuration
at the C2 atom. The amide group of the substrate is hydrogen-bonded with the
hydroxy group of S118. The methyl group bound to the C2 atom exists in a
hydrophobic pocket which is important for recognition of the alkyl group of the
substrate. The guanidino group of R41 has reasonable orientation for halogen
abstraction.
PMID- 9644240
TI - The human PTFgamma/SNAP43 gene: structure, chromosomal location, and
identification of a VNTR in 5'-UTR.
AB - PTF/SNAPc is a multisubunit complex which specifically recognizes the PSEs of
small nuclear RNA genes and activates transcription by RNA polymerase II or III.
Here we describe the isolation and characterization of genomic clones encoding
the human PTFgamma/SNAP43 gene. The gene spans approximately 29 kilobases, and is
composed of 9 exons and 8 introns. A major transcription initiation site was
identified at the position 58 base pairs upstream of the AUG translation
initiator codon on primer extension analysis with HeLa mRNA. The 5' flanking
region lacks a typical TATA box but contains many putative binding sites for
various transcription factors, such as Sp1, Oct1, NF1, AP1, E2F, and USF.
Immediately downstream of the transcription start site, we found a VNTR of a 17
bp sequence rich in (G+C). Four different alleles with two to five copies of the
tandem repeat were identified in 10 individuals examined, indicating a high
degree of variation at the PTFgamma/SNAP43 locus. In addition, the
PTFgamma/SNAP43 gene was mapped to human chromosome 14q22 by fluorescence in situ
hybridization.
PMID- 9644241
TI - Stable isotope-edited NMR analysis of Ascaris suum mitochondrial tRNAMet having a
TV-replacement loop.
AB - Most nematode mitochondrial (mt) tRNAs have a TV-replacement loop (TV loop) which
replaces the normal T arm and the variable loop in standard tRNAs with a less
structured loop. The tertiary structure of such tRNAs has been discussed
theoretically with reference to the crystal structure of yeast tRNAPhe
[Wolstenholme et al. (1994) Nucleic Acids Res. 22, 4300-4306] and examined
experimentally by chemical and enzymatic probing [Watanabe et al. (1994) J. Biol.
Chem. 269, 22902-22906]. The results suggest that most regions of the tRNA other
than the TV loop are folded in a similar manner to yeast tRNAPhe. To confirm this
notion more clearly, the tertiary structure of Ascaris suum mt tRNAMet was
analyzed by NMR using various synthetic tRNAs site-specifically labeled with
stable isotopes, which were prepared by a combination of chemical synthesis and
enzymatic ligation. Tertiary interactions involving G(L2), G(L3), U(L4), and U8
were observed in the NMR spectra of the labeled tRNAs, but those relating to
G(L5) were not. On the basis of these results, a possible tertiary structural
model of nematode mitochondrial tRNAMet was constructed.
PMID- 9644242
TI - Cloning of human polyubiquitin cDNAs and a ubiquitin-binding assay involving its
in vitro translation product.
AB - During large-scale in vitro translation analysis of a human full-length cDNA
bank, we found a clone producing a remarkably smaller translation product than
that expected from the open reading frame. The cDNA encodes a polyubiquitin, UbC,
composed of nine tandem repeats of the ubiquitin unit. The bank contained twelve
UbC cDNAs including four full-length ones. Sequencing analysis of these clones
showed that UbC cDNAs can be classified into two types, UbC1 and UbC2, in each of
which there are six polymorphic nucleotide variations. The present UbC cDNA was
in vitro translated in a rabbit reticulocyte or wheat germ extract to produce a
free ubiquitin labeled with [35S]methionine. The labeled ubiquitin could be used
as a substrate for thiol ester formation with ubiquitin-activating enzyme E1 or
ubiquitin-conjugating enzyme E2.
PMID- 9644243
TI - Lower mevalonate pyrophosphate decarboxylase activity is caused by the reduced
amount of enzyme in stroke-prone spontaneously hypertensive rat.
AB - Spontaneously hypertensive rat (stroke-prone) (SHRSP) has a low serum cholesterol
level as compared with the normotensive Wistar Kyoto rat (WKY). We previously
indicated that the lower activity of mevalonate pyrophosphate decarboxylase (MPD)
was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP
[Sawamura et al. (1992) J. Biol. Chem. 267, 6051-6055]. To elucidate the
mechanism of the reduced activity, we purified liver MPD from SHRSP treated with
cholestyramine and pravastatin in this study. We compared its enzymatic
properties with those of the enzyme from WKY, and also measured the amounts of
MPD in the crude extract of various tissues in WKY and SHRSP by Western blot
analysis. Results indicated that (i) MPD of SHRSP has essentially the same
properties as MPD of WKY, except for a difference in the dependency on divalent
cations. (ii) The amount, as well as the activity, of MPD in the crude extract of
brain and liver was reduced in SHRSP. (iii) There was no difference between SHRSP
and WKY, in the ratio of the enzyme activity to the amount of MPD in the crude
extract. These data led us to conclude that the lower activity of MPD was caused
by the reduced amount of this enzyme in SHRSP.
PMID- 9644244
TI - Lysyl-tRNA synthetase from Bacillus stearothermophilus. Stopped-flow kinetic
analysis of enzyme.lysyladenylate formation.
AB - Amino acid activation reaction of the lysyl-tRNA synthetase [L-lysine:tRNALys
ligase (AMP forming); EC 6.1.1.6] from Bacillus stearothermophilus was studied
fluorometrically by the stopped-flow method. The addition of L-lysine to the
enzyme solution caused quenching of the protein fluorescence and the subsequent
addition of ATP restored the quenched fluorescence [Takita et al. (1996) J.
Biochem. 119, 680-689; Takita et al. (1997) 121, 244-250]. In the stopped-flow
analysis, however, the former fluorescence change (quenching) could not be
detected, while the latter change (restoration) was detectable. The L-lysine
binding process was suggested to be much faster than the ATP binding process,
being completed within the dead-time of the apparatus, ca. 3 ms. The hyperbolic
dependence of kapp on the initial ATP concentration suggested that the ATP
binding to the enzyme.L-lysine complex followed a two-step mechanism. Two L
lysine analogues that exhibit the qualitatively similar behavior to L-lysine in
the fluorometric titration, L-lysine hydroxamate and L-lysine amide, were
examined similarly. The two-step process was also suggested for these analogues,
and the forward rate constant in the rate-determining step for L-lysine amide
(221+/-7 s-1) was significantly larger than those for L-lysine (45.7+/-4.6 s-1)
and L-lysine hydroxamate (14. 5+/-1.7 s-1) at pH 8.0, 30 degrees C.
PMID- 9644245
TI - Characterization of a multi-copper enzyme, nitrous oxide reductase, from
Rhodobacter sphaeroides f. sp. denitrificans.
AB - The nitrous oxide reductase from the photodenitrifier, Rhodobacter sphaeroides f.
sp. denitrificans, has been purified. The enzyme is composed of two identical
subunits of 66 kDa, and contains four copper atoms per subunit. Copper
supplementation of the medium resulted in a 3.5-fold increase in the enzyme yield
with doubly enhanced specific activity. The activity of the purified nitrous
oxide reductase was completely inhibited by 100 microM zinc ions.
PMID- 9644246
TI - Molecular cloning, expression, and characterization of a novel mouse liver
SULT1B1 sulfotransferase.
AB - A mouse liver homogenate was shown to contain enzymatic activities catalyzing the
sulfation of 3,4-dihydroxyphenylalanine (Dopa) and tyrosine isomers with a pH
optimum of 8.25. Western blot analysis revealed a 34 kDa protein exhibiting
immunologic cross-reactivity to antiserum against rat liver SULT1B1
sulfotransferase. By employing the reverse transcriptase-polymerase chain
reaction (RT-PCR) technique, a 910-base pair product encoding the putative mouse
liver SULT1B1 sulfotransferase was obtained. Using this PCR product as a probe, a
cDNA containing the entire open reading frame of the mouse liver SULT1B1
sulfotransferase was cloned from a mouse liver Lambda ZAP cDNA library. The
nucleotide sequence indicated it is a new enzyme. The deduced amino acid sequence
exhibited 87.6, 72.3, 55.9, 54.2, 52.8, 51.1, and 49.4% identity to the amino
acid sequences of the rat liver SULT1B1 sulfotransferase, human thyroid hormone
sulfotransferase, mouse phenol sulfotransferase, rat liver phenol
sulfotransferase, rat liver hydroxyarylamine sulfotransferase, mouse estrogen
sulfotransferase, and rat estrogen sulfotransferase. Upon transfection of COS-7
cells with an expression vector (pcDNA3) harboring the cDNA encoding this new
enzyme, a 34 kDa protein exhibiting immunologic cross-reactivity to antiserum
against the rat liver SULT1B1 sulfotransferase was expressed. The recombinant
sulfotransferase exhibited enzymatic activities toward Dopa and tyrosine isomers,
as well as dopamine and 3,3',5-triiodo-L-thyronine. Northern blot analyses
indicated the SULT1B1 sulfotransferase was predominantly expressed in liver, but
not in the other ten mouse organs examined. Furthermore, the enzyme was found to
be expressed in a developmental stage-dependent manner, being at a very low level
in liver samples from 1-day-old mice and then gradually increasing to the maximum
level in liver samples from 4-week-old mice.
PMID- 9644247
TI - Induction of metallothionein isoforms in rat hepatoma cells by various anticancer
drugs.
AB - The induction of metallothionein (MT) isoforms (MT-1, -2) by anticancer drugs was
investigated in cultured rat hepatoma H4 II E C3 cells. The steady-state
expression of MT-1 mRNAs was higher than that of MT-2 mRNAs. During incubation of
the cells with various anticancer drugs, namely, adriamycin, epirubicin, cis
diamminedichloroplatinum(II) (CDDP), and cis-diammine(1, 1
cyclobutyldicarboxylato)platinum(II), both MT-1 and MT-2 mRNAs were coordinately
inducible: the levels of isoMT mRNA reached a maxim of approximate by 6-fold at 3
h. Immunofluorescent studies revealed that the cytosolic fluorescence in the
cells exposed to 1 microM CDDP for 48 h was more intensified than that in the
untreated cells. Transfer of antisense oligonucleotides resulted in marked
reduction of isoMT mRNA, and upon exposure to 5 microM CDDP for 48 h, the
viabilities of these cells dropped to 25.8% of the controls. These results
indicate that anticancer drugs are potent inducers of MT isoforms in hepatoma
cells and that a decrease in cellular MTs enhances the susceptibility of hepatoma
cells to CDDP. Thus, we conclude that endogenous MTs play a role in determining
the sensitivity or resistance of cancer cells to clinically important anticancer
agents.
PMID- 9644248
TI - Effects of nitration and amination of tyrosyl residues in thermolysin on its
hydrolytic activity and its remarkable activation by salts.
AB - Thermolysin is remarkably activated in the presence of high concentrations (1-5
M) of neutral salts and its activity is enhanced 15 times by 4 M NaCl at pH 7.0
and 25 degrees C [Inouye, K. (1992) J. Biochem. 112, 335-340]. In this study, the
effects of nitration and amination of tyrosyl residues in thermolysin on its
halophilic properties were examined. Nitration and successive amination
inactivate thermolysin progressively as the degree of modification increases.
When 16 tyrosyl residues were nitrated, the activity decreased to 10% of that of
the native enzyme, whereas it recovered to 30% when they were aminated. The
decrease in the activity by the nitration and amination was shown to be brought
about only by a decrease in the molecular activity, kcat; the Michaelis constant,
Km, was unaltered. When 14 tyrosyl residues of thermolysin were nitrated, the
degree of activation by 4 M NaCl at pH 7.0 decreased from 15 to 10, and this
decreased further to 5 when the pH of the reaction medium was raised to 8.5.
However, when the nitrated tyrosyl residues were reduced to aminotyrosyl
residues, the degree of activation was restored to that of the native enzyme. The
change in the degree of activation by nitration and amination of thermolysin
could be due to the change in the ionization of tyrosyl residues, and it was
suggested that removing negative charges from tyrosyl residues of thermolysin
enhances its halophilicity.
PMID- 9644249
TI - Molecular cloning, expression, and site-directed mutagenesis of inorganic
pyrophosphatase from Thermus thermophilus HB8.
AB - The genomic DNA encoding the inorganic pyrophosphatase from an extremely
thermophilic bacterium, Thermus thermophilus HB8 (ATCC27634), was isolated by
colony hybridization with a probe designed as a part of gene amplified by the PCR
method, which was derived from the partial amino acid sequence of the enzyme. The
DNA was cloned into a plasmid vector, pUC118, after digestion with BamHI. The
inserted nucleotide fragment was about 1.8 kbp in length and the nucleotide
sequence included a 525 bp open reading frame. The deduced amino acid sequence
was completely identical with that of the enzyme determined by automated Edman
analysis of peptide fragments isolated from digests obtained with Staphylococcus
aureus V8 protease and Achromobacter protease I, and also from products obtained
on chemical cleavage with cyanogen bromide and 70% formic acid. The subunit of
this enzyme is composed of 174 amino acid residues with a calculated molecular
weight of 19,084. Then, the gene was overexpressed in Escherichia coli BL21 (DE3)
using a plasmid vector, pET15b, system. The recombinant enzyme was fully active,
and exhibited higher thermostability than the E. coli enzyme. Amino acid residues
located on the surface of the recombinant enzyme were determined by means of
limited proteolysis, and the results revealed that the environment of Lys
residues is almost the same as the crystal structure reported previously
[Teplyakov, A. et al. (1994) Protein Sci. 3, 1098-1107]. Furthermore, the roles
of two tryptophan residues were investigated by site-directed mutagenesis, which
indicated that they may be responsible for the structural integrity and
thermostability.
PMID- 9644250
TI - Promoter selectivity of the Bacillus subtilis RNA polymerase sigmaA and sigmaH
holoenzymes.
AB - The sigmaH of Bacillus subtilis directs transcription of a large number of early
sporulation genes, whereas the principal sigma factor, sigmaA, is essential for
the transcription of the genes for vegetative growth and early sporulation. We
have purified sigmaA and sigmaH proteins, and characterized their properties. The
genes encoding sigmaA or sigmaH were separately cloned into an expression vector
under the control of T7 promoter. Both proteins were overproduced in Escherichia
coli BL21(DE3) and purified from inclusion bodies after solubilization with
guanidine hydrochloride. Antigenicities and N-terminal amino acid sequences of
the overproduced proteins were used to identify both proteins. Unlike sigmaA
protein, sigmaH protein showed a DNA-binding ability. To compare the promoter
selectivity of the sigmaA protein with that of the sigmaH protein, transcription
in vitro of 16 promoters was performed using RNA polymerase holoenzymes
reconstituted from a purified core enzyme with either sigmaH or sigmaA. These
holoenzymes correctly recognized each of the cognate promoters; sigmaH-RNA
polymerase recognized sigmaH promoters but not sigmaA promoters, and vice versa.
A competition experiment for core RNA polymerase using sigmaA and sigmaH revealed
that sigmaA had a stronger affinity. We propose that the predicted replacement of
a sigma subunit in a holoenzyme from sigmaA to sigmaH in vivo at late logarithmic
growth phase may require an additional factor, or the modification of a core
enzyme or sigma factor.
PMID- 9644251
TI - Feedback loops involving Spo0A and AbrB in in vitro transcription of the genes
involved in the initiation of sporulation in Bacillus subtilis.
AB - Through mainly in vivo studies, the initiation of sporulation in Bacillus
subtilis has been shown to depend on the phosphorylation of the Spo0A
transcription factor mediated by the multicomponent phosphorelay via KinAB (C),
Spo0F, Spo0B, and Spo0A in this order. RNA polymerase containing sigmaA (EsigmaA)
or sigmaH (EsigmaH) transcribes the genes of the phosphorelay components.
Phosphorylated Spo0A is also involved in their expression and is required for the
induction of sigmaH by repressing its repressor gene abrB. We have examined the
effects of phosphorylated Spo0A (Spo0A-P) and AbrB on in vitro transcription of
the genes involved in the Spo0A phosphorylation and initiation of sporulation.
Spo0A-P repressed EsigmaA-dependent transcription of the kinC and EsigmaH
dependent transcription of spo0A and kinA. EsigmaH-dependent transcription of
spo0F was stimulated by Spo0A-P at low concentrations but was repressed by higher
amounts of Spo0A-P. On the other hand, AbrB repressed EsigmaA-dependent
transcription of spo0H (sigmaH gene), kinC, and abrB, although its effect was not
strong. With the present results providing in vitro evidence for the roles of
Spo0A-P and AbrB as transcriptional regulators, and other results described in
the literature, the positive and negative feedback loops controlling the temporal
expression of early sporulation genes are discussed.
PMID- 9644252
TI - Further characterization of hydrogen peroxide-dependent fatty acid alpha
hydroxylase from Sphingomonas paucimobilis.
AB - Although fatty acid alpha-hydroxylase (FAAH) activity has been detected in
various species, FAAH has not been sufficiently characterized. In this report, we
describe the properties of FAAH highly purified from Sphingomonas paucimobilis.
The FAAH was purified by about 5,200-fold. Blotting analysis with a specific
antibody against the FAAH showed that its apparent molecular mass was
approximately 43 kDa. FAAH showed alpha-hydroxylation activity in the presence of
H2O2, but little if any activity with cumene hydroperoxide, t-butyl
hydroperoxide, or t-butyl peroxybenzonate. The Km value for H2O2 was 72 microM.
Highly purified FAAH oxidized various non-esterified saturated and unsaturated
fatty acids including myristic acid, but not myristoyl-CoA. Potassium cyanide and
sodium azide inhibited the FAAH activity in a concentration-dependent manner.
Other respiratory chain inhibitors such as rotenone and antimycin A did not
inhibit the activity. Among cytochrome P450 inhibitors, SKF-525A markedly
inhibited the activity at the concentration of 2 mM, but CO did not. Imidazole,
an inhibitor of plant alpha-oxidation, showed no inhibitory effect at 1 mM.
PMID- 9644253
TI - Characterization of the enzymatic 7-O-acetylation of sialic acids and evidence
for enzymatic O-acetyl migration from C-7 to C-9 in bovine submandibular gland.
AB - Microsomes prepared from bovine submandibular glands incubated with radioactive
AcCoA incorporated acid-insoluble radioactivity, which was dependent on time, and
the concentrations of AcCoA and proteins, and was inhibited by CoA in a
concentration-dependent manner. Under the conditions used, the apparent Km for
AcCoA was 1.63 microM with a Vmax of 21.9 pmol/mg protein.min. The radioactivity
incorporated was mainly due to the O-acetylation of glycosidically bound Neu5Ac.
The primary attachment site of O-acetyl groups was exclusively the hydroxyl at C
7 of Neu5Ac, the presence of an AcCoA:Neu5Ac 7-O-acetyltransferase thus being
demonstrated. After longer incubation 9-O-acetylated Neu5Ac also appeared,
suggesting the migration of an ester group from C-7 to C-9. This isomerisation
was inhibited by heat-inactivation of the microsomal protein, enzymatic
isomerisation by a "migrase" thus being suggested. Data are presented which lead
to the assumption that this 7-O-acetylation involves at least two reactions: the
transport by a translocase of acetyl groups from AcCoA from the cytosol across
the Golgi membrane, followed by the enzymatic transfer of these acetyl groups
onto sialic acids in the Golgi lumen.
PMID- 9644254
TI - Amino-terminal region of SecA is involved in the function of SecG for protein
translocation into Escherichia coli membrane vesicles.
AB - Protein translocation across the cytoplasmic membrane of Escherichia coli is
accomplished by concerted actions of the translocation ATPase SecA and the
membrane-embedded SecE/Y/G complex. SecA interacts with preproteins and undergoes
ATP-driven cycles of membrane insertion-deinsertion. To address how SecA
interacts functionally with other components in the translocation machinery, we
characterized a SecA mutant lacking amino-terminal 8 amino acid residues (SecA N
8). Although the absence of the 8 residues did not grossly affect the interaction
of SecA with a preprotein, ATP, or phospholipids, nor did it affect the intrinsic
ATPase activity, it gave differential effects on the translocation of different
preproteins. It also affected the translocation ATPase activity, the ability of
membrane insertion, and the topology inversion of SecG coupled with the membrane
insertion-deinsertion of SecA. Most noteworthy, SecA N-8 was pronouncedly
defective in the translocation of proton motive force-dependent preproteins, in
which SecG might have a role. We propose that the amino-terminal region of SecA
is important for the functional interaction with SecG.
PMID- 9644255
TI - Inhibition of endogenous expression of connective tissue growth factor by its
antisense oligonucleotide and antisense RNA suppresses proliferation and
migration of vascular endothelial cells.
AB - Previously, we cloned an mRNA predominantly expressed in hypertrophic
chondrocytes by differential display-PCR from a human chondrosarcoma-derived
chondrocytic cell line (HCS-2/8) that is identical to that of connective tissue
growth factor (CTGF). In the present study, we investigated the roles of CTGF in
the proliferation and migration of vascular endothelial cells using its antisense
oligonucleotide and antisense RNA, because angiogenesis into the hypertrophic
zone of cartilage occurs at the final step of endochondral ossification.
Immunohistochemical and immunofluorescence techniques revealed that not only
hypertrophic chondrocytes but also endothelial cells in the cost-chondral
junctions of mouse ribs were stained with an anti-CTGF antibody in vivo. Northern
blot analysis revealed that CTGF was strongly expressed in chondrocytic cells as
well as bovine aorta endothelial (BAE) cells in culture, but not in other types
of cells such as osteoblastic cells. Its expression in BAE cells was greater in
the growing phase than in the confluent phase. When one-half of a monolayer of a
confluent culture of BAE cells had been peeled off, only the cells proliferating
and extending into the vacant area were stained with the anti-CTGF antibody. The
addition of an antisense oligonucleotide inhibited the proliferation and
extension of the BAE cells into the vacant area. The antisense oligonucleotide
also inhibited the proliferation of BAE cells in the rapidly proliferating phase.
In a Boyden chamber assay, pretreatment with the antisense oligonucleotide
markedly inhibited the migration of BAE cells. Furthermore, the abilities to
proliferate and migrate of BAE cells, which were stably transfected with
expression vectors that generate the antisense RNA of CTGF cDNA, were markedly
lower than those of the control. These findings suggest that endogenous CTGF
expression is involved in the proliferation and migration of BAE cells.
PMID- 9644256
TI - Substrate specificities and kinetic properties of proteinase A from the yeast
Saccharomyces cerevisiae and the development of a novel substrate.
AB - The substrate specificities and kinetic properties of proteinase A, an
intracellular aspartic proteinase from the yeast Saccharomyces cerevisiae, were
determined using a series of synthetic chromogenic peptides with the general
structure P5-P4-P3-P2-Phe-(NO2)Phe-P2'-P3' [P5, P4, P3, P2, P2', P3' are various
amino acids; (NO2)Phe is p-nitro-L-phenylalanine]. The nature of the residues
occupying the NH2-terminal region of the substrate had a strong influence on the
kinetic constants. Among those tested, Ala-Pro-Ala-Lys-Phe-(NO2)-Phe-Arg-Leu had
the best kinetic constants (Km = 0.012 mM, kcat = 14.4 s-1, kcat/Km = 1,200 M-1.s
1). Compared with such aspartic proteinases as pepsin, cathepsin D, and renin,
the substrate specificity of proteinase A was unique. Based on these results, a
novel fluorescent substrate, MOCAc-Ala-Pro-Ala-Lys-Phe-Phe-Arg-Leu-Lys(Dnp)-NH2,
was developed for the sensitive measurement of proteinase A.
PMID- 9644257
TI - Glycosylation of amphipathic lactoside primers with consequent inhibition of
endogenous glycosphingolipid synthesis.
AB - The incubation of amphipathic lactosides with cultured cells was found to prime
the glycosylation of lactosides whose oligosaccharide structures were exactly the
same as those of glycosphingolipids produced by cells: B16 melanoma cells
produced alpha2-3 sialylated lactosides; and PC12 cells, Galalpha1-4- and
Galalpha1-3Galalpha1-4lactosides. Analysis of the cell-associated glycosylated
products indicated that C16 series lactoside primers function 5-6 times more
efficiently as acceptors than C12 series primers. The glycosylated lactosides
were also secreted into the culture medium. Lactoside primers with longer
hydrophobic chains hampered the release of glycosylated products from cells. The
presence of an N-acyl chain in the lipophilic moiety of primers suppressed the
secretion of glycosylated products. Owing to its overall availability, lactosides
with the C12 alkyl chain were glycosylated 2-3 times more than C16 series
lactosides and 1.4 times more than lactosides with the C12 acyl chain. C8
lactosides did not function as primers under the conditions of this study, but
they were found to be the best acceptors for sialic acid transfer with the
soluble enzyme fraction. The incubation of cells with 10 microM N
hexadecanoylaminoethyl-beta-O-lactoside caused a 30% decrease in endogenous GM3
of B16 cells and a 34% decrease in Gb3Cer synthesis of PC12 cells. The results of
the present study demonstrate that lactoside primers serve as an efficient means
to inhibit endogenous glycosphingolipids in studies to clarify glycosphingolipid
functions.
PMID- 9644258
TI - Kinetic characterization of lysine-specific metalloendopeptidases from Grifola
frondosa and Pleurotus ostreatus fruiting bodies.
AB - Two zinc-metalloendopeptidases, GFMEP (accession number P81054) and POMEP
(accession number P81055), from the fruiting bodies of two edible mushrooms,
Grifola frondosa and Pleurotus ostreatus, respectively, specifically hydrolyze
peptidyl-lysine bonds (-X-Lys-) in polypeptides. To understand detailed substrate
specificities and kinetic characters of these enzymes, we have synthesized
various intramolecularly quenched fluorescent peptide substrates and determined
their kinetic constants with these substrates. Each synthesized fluorogenic
peptide has a fluorescent residue, tryptophan, at its carboxyl terminus and a
quenching group, dinitrophenyl (Dnp), at its amino terminus. Quenching of the Trp
fluorescence in an intact substrate is relieved on hydrolysis of the -X-Lys-
bond, giving rise to a continuous increase in fluorescence. The octapeptide
substrate, Dnp-Ser-Thr-Ala-Thr-Lys-Leu-Ser-Trp, was an efficient substrate for
both enzymes, the kcat/Km values being 9.8 x 10(6) and 7.0 x 10(5) M-1.s-1 for GF
and POMEP, respectively. Peptides with aspartic acid adjacent to the Lys residue
were found to be poor substrates for both enzymes. Neither the shortest peptide,
Dnp-Thr-Lys-Trp, nor peptides with substitution of L-Arg, L-ornithine, or D-Lys
for Lys were hydrolyzed by either enzyme. These results confirmed the strict
specificities of GF- and POMEP toward the peptide bond, -X-Lys-. Substitution of
Co2+ for Zn2+ enhanced the activity, while the Km values were comparable. All
peptides not hydrolyzed by either enzyme had inhibitory effects on GFMEP
activity. The active site structure is discussed in relation to these
observations.
PMID- 9644259
TI - Conformation, filament assembly, and activity of single-headed smooth muscle
myosin.
AB - Single-headed myosin was prepared by digestion of porcine aorta smooth muscle
myosin with Staphylococcus aureus V8 protease in the presence of actin. The
single-headed myosin preparation contained intact light chains, a rod fragment of
a heavy chain, and a heavy chain of which only a minor fraction contained a nick
in the head segment. Below 0.2 M NaCl, the single-headed myosin showed a decrease
in Ca2+-ATPase activity and an increase in the elution time on gel filtration
HPLC in a phosphorylation-dependent manner, indicating a phosphorylation
dependent conformational transition between the extended and folded forms. These
conformations were confirmed by electron microscopic observation of rotary
shadowed samples of single-headed myosin. However, the conformational transition
of single-headed myosin occurred in a narrower range with lower salt
concentrations than that of double-headed myosin. The filament assembly of single
headed myosin was thus facilitated and phosphorylation-independent. The single
headed myosin also showed high actin-activated ATPase activity independent of
phosphorylation. These results indicate that the two-headed structure of smooth
muscle myosin is not essential for the conformational transition, but is required
for the phosphorylation-dependent regulation of enzymatic activity and filament
assembly.
PMID- 9644260
TI - Functional expression of human golgi CMP-sialic acid transporter in the Golgi
complex of a transporter-deficient Chinese hamster ovary cell mutant.
AB - We recently described the cloning of putative human CMP-sialic acid transporter
(hCST) cDNA [Ishida, N. et al. (1996) J. Biochem. 120, 1074-1078]. The hCST cDNA
coded for a hydrophobic protein with an amino acid sequence showing a high degree
of similarity (92% identity) to that of murine CMP-sialic acid transporter. In
this report, we demonstrate that hCST corrects the CMP-sialic acid transporter
deficient phenotype of CHO-derived Lec2 cells, as judged from the recovery of WGA
sensitivity by transformants, and the recovery of CMP-sialic acid transporting
ability by microsomal vesicles prepared from them. A peptide antibody against the
C-terminus of the hCST protein detected the cDNA products expressed in the
microsomes of the transformants. The subcellular localization of the hCST protein
in the Golgi membrane was demonstrated by immunofluorescence microscopy, using
the hCST-specific antibody. These results clearly indicate that hCST cDNA encodes
the human CMP-sialic acid transporter protein. Plasma membrane-selective
permeabilization combined with immunofluorescence microscopy provided strong
evidence that the C-terminus of the human CMP-Sia transporter is exposed to the
cytosol on the outer surface of the Golgi membrane.
PMID- 9644261
TI - Changes with age of the rat fetuin concentration in serum and its mRNA
expression.
AB - Rat fetuin, a counterpart of human alpha2-HS glycoprotein and bovine fetuin,
shows strong intermolecular binding and association with other serum proteins.
Therefore, to measure its concentration in rat serum, we pretreated serum samples
with 1% SDS plus 5% (ca. 0.7 M) 2-mercaptoethanol at 100 degrees C for 3 min, and
then subjected them to SDS-PAGE under reducing conditions followed by Western
blotting. We found that the fetuin concentrations in normal rat serum determined
by Western blotting were 2.5-4.5 mg/ml. These concentrations were three orders of
magnitude higher than the previously reported concentrations. We also tried to
measure the fetuin concentration in rat serum by means of an enzyme-linked
immunosorbent assay after treatment of the samples with 0.1% sodium dodecyl
sulfate (SDS) plus 10 mM 2-mercaptoethylamine at 100 degrees C for 3 min, but it
gave a value of about 1/4 of that on Western blotting. Rat fetuin is expressed
mainly in the liver, with a peak 2-4 weeks after birth, as determined by Northern
blot analysis. The fetuin mRNA level in the liver changes almost in parallel with
its serum concentration. The tibia also expresses fetuin, but much less than the
liver.
PMID- 9644262
TI - Evidence for chloramphenicol/H+ antiport in Cmr (MdfA) system of Escherichia coli
and properties of the antiporter.
AB - We detected chloramphenicol/H+ antiport activity in membrane vesicles of
Escherichia coli and cloned a gene for the antiporter from chromosomal DNA of E.
coli. Introduction of the gene into E. coli cells conferred resistance to
chloramphenicol and ethidium. A slight increase in resistance to acridine orange
was also observed. Elevated chloramphenicol efflux and ethidium efflux were
observed in cells harboring a plasmid carrying the gene. Addition of
chloramphenicol to the assay mixture reduced the efflux of ethidium. Elevated
chloramphenicol/H+ antiport activity was observed in membrane vesicles prepared
from cells harboring the plasmid. The pH optimum for the activity was 6.5. We
sequenced the gene and deduced the amino acid sequence of its product. A sequence
homology search revealed that it was same as that of Cmr (or MdfA). Thus, it
became clear that Cmr (MdfA) is the chloramphenicol(and ethidium)/H+ antiporter.
PMID- 9644263
TI - Antibody against ganglioside GD1c containing NeuGcalpha2-8NeuGc cooperates with
CD3 and CD4 in rat T cell activation.
AB - Gangliosides have long been implicated in T cell activation. GD1c with two N
glycolylneuraminic acids [GD1c(NeuGc,NeuGc)] is the predominant ganglioside in
rat T cells. In the present study, the anti-GD1c(NeuGc,NeuGc) mAb, AC1, which
binds to the NeuGcalpha2-8NeuGcalpha2- sequence, was found to enhance Con A
activated cellular proliferation at a concentration at which AC1 alone did not
activate the cells. The potentiation by AC1 was observed more consistently and
effectively in the cellular activation elicited by cross-linking of anti-CD3 and
anti-CD4, rather than in the cell growth induced by immobilized anti-CD3 alone.
Moreover, the combination of immobilized anti-CD4 and soluble AC1 had a
remarkable mitogenic effect. In addition, we have demonstrated the existence of a
100 kDa protein in rat T cell lysates which reacts with AC1 on Western blots, and
this interaction is abolished by sialidase-treatment of the membrane. Pronase
treatment of the T cells, which rendered the 100 kDa protein undetectable on
Western-blotting, reduced the number of AC1-positive cells by 40-50% on flow
cytometry. On the other hand, all cells became AC1-negative after sialidase
treatment. These findings indicated that AC1 reacts with both GD1c(NeuGc,NeuGc)
and the 100 kDa glycoprotein on rat T cells. Taken together, these results
predict the presence of a novel regulatory mechanism of T cell activation
involving CD4 and the NeuGcalpha2-8NeuGcalpha2- sequence.
PMID- 9644264
TI - Resonance Raman study on reduced flavin in purple intermediate of flavoenzyme:
use of [4-carbonyl-18O]-enriched flavin.
AB - 4-Carbonyl-18O]-enriched lumiflavin, riboflavin, and FMN were prepared by
incubating each corresponding non-labeled flavin in 1 M Na18OH (H218O) at 25
degrees C. [4-Carbonyl-18O]FAD was prepared from the corresponding riboflavin by
using FAD synthetase. Isotope effects by [4-carbonyl-18O]-labeling confirmed that
the 1,709-cm-1 band in the IR spectrum of lumiflavin and the 1,711-cm-1 band in
the Raman spectrum of FAD are mainly derived from C(4)=O stretching vibrational
mode. The 1,605-cm-1 Raman band of the anionic reduced flavin in the purple
intermediate of D-amino acid oxidase (DAO) with D-proline or D-alanine does not
shift in DAO reconstituted with [4-carbonyl-18O]FAD, although it shifts with
[4,10a-13C2]- or [4a-13C]FAD. Thus the band is mainly due to the C(4a)=C(10a)
stretching vibrational mode and includes no contribution from C(4)=O stretching
vibration. The band frequencies cover a fairly wide range (1,602-1,620 cm-1)
depending on the enzymes. The frequencies of the reduced flavin in the purple
intermediates of the dehydrogenases (medium-chain acyl-CoA, short-chain acyl-CoA,
and isovaleryl-CoA dehydrogenases) are higher than those of the oxidases (DAO and
L-phenylalanine oxidase). This indicates that the C(4a)=C(10a) bond order of
reduced flavin in the dehydrogenases with the low reactivity for molecular oxygen
is stronger than that in the oxidases with high reactivity. Therefore, the band
frequency of C(4a)=C(10a) stretching may serve as an indicator of the reactivity
of flavoprotein with molecular oxygen. Furthermore, strong hydrogen bonding of
flavin at the N(1) moiety with the hydroxyl group of Thr136 in MCAD is probably
responsible for the strong bond of the C(4a)=C(10a) of reduced flavin in the
dehydrogenase.
PMID- 9644265
TI - Involvement of stromal membrane-associated protein (SMAP-1) in erythropoietic
microenvironment.
AB - Erythropoiesis is regulated by the hematopoietic microenvironment of the spleen
and fetal liver in mice. We showed that established stromal cells of these organs
selectively support erythropoiesis in vitro. To identify the cell surface
molecule(s) on the stromal cells involved in erythropoiesis, we raised monoclonal
antibodies against the stromal cells. Using one of these antibodies (11D), we
cloned a new gene named smap-1 (stroma membrane-associated protein-1). The SMAP-1
protein deduced from the nucleotide sequence of the cDNA was a newly identified
membrane protein with direct repeats of the KKD/E units found in MAP1A and MAP1B,
which is involved in the association with microtubules. By transfection of the
anti-sense smap-1 cDNA into the stromal cells, we showed that SMAP-1 may have a
stimulatory effect on stroma-supported erythropoiesis. Its expression was
detected in the yolk sac, fetal liver, spleen, and bone marrow, and was
correlated with their erythropoietic activity.
PMID- 9644266
TI - Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding
Ad4BP/SF-1 is independent of pituitary control.
AB - Ad4BP/SF-1 is a transcription factor essential for the development of the adrenal
gland and the gonads as well as for the maintenance of their functions through
regulating tissue-specific gene transcription. In the whole body, hypothalamo
pituitary-gonadal and -adrenal axes are known to play prominent roles in
mediating the function of the gonads and adrenal. In this study, the effects of
the tropic peptide hormones secreted by the pituitary on the regulation of the
rat Ftz-F1 (rFtz-F1) gene encoding Ad4BP/SF-1 were investigated. Immunochemical
studies revealed that Ad4BP/SF-1 was expressed even in the adrenal cortex of
hypophysectomized rats. Such persistent expression of Ad4BP/SF-1 was also
observed in the testes and ovaries of the hypophysectomized animals. In contrast
to Ad4BP/SF-1, the expressions of steroidogenic P450s were reduced significantly.
The transcriptional activities of the endogenous and transfected rFtz-F1 genes
were examined with Y-1 and I-10 cells derived from mouse adrenocortical and
testicular Leydig cell tumors, respectively. Neither gene appeared to be
activated significantly by cAMP, whereas both endogenous and exogenous CYP11A
genes encoding P450(SCC) were activated. Taken together, these observations
indicate that the expression of the rFtz-F1 gene is mainly regulated by a
mechanism independent of the neuroendocrine axes.
PMID- 9644267
TI - Activation of protein phosphatase 2A by the Fe2+/ascorbate system.
AB - Freshly isolated protein phosphatase 2A (PP2A) was highly active as to the
dephosphorylation of protein substrates, but lost most of its spontaneous
activity on prolonged storage, and was converted to a latent form requiring Mn2+
or Co2+ ions for activity. In this report, we show that the latent form of PP2A
can be activated by the Fe2+/ascorbate system. Activation of the phosphatase
required both Fe2+ ions and ascorbate, and the level of activation was dependent
on the concentrations of both Fe2+ ions and ascorbate. Both the holoenzyme and
catalytic subunit of phosphatase 2A could be activated by the Fe2+/ascorbate
system, indicating that direct modulation of the catalytic subunit of the
phosphatase by the Fe2+/ascorbate system may cause this activation. Several
common divalent metal ions, including Ca2+, Mg2+, Cu2+, Zn2+, and Ni2+ ions,
cannot cooperate with ascorbate to activate the phosphatase. Dithiothreitol, a SH
containing reducing agent, could replace ascorbate in the Fe2+/ascorbate system
to activate the phosphatase, whereas H2O2, a strong oxidizer, significantly
diminished the phosphatase activation by the Fe2+/ascorbate system. The results
indicate that iron ions stabilized in the +2 state by reducing agents can
activate the phosphatase. Overall, the present study provides initial biochemical
evidence suggesting that Fe2+ could be a biologically important metal ion
cofactor responsible for PP2A activation.
PMID- 9644268
TI - Development of a sensitive and accurate enzyme-linked immunosorbent assay (ELISA)
system that can replace HPLC analysis for the determination of N1,N12
diacetylspermine in human urine.
AB - N1,N12-Diacetylspermine (DiAcSpm)-specific antibodies were raised in rabbits,
using N-acetylspermine coupled to mercaptosuccinylated BSA via N-(4
maleimidobutyryloxy)-succinimide as an antigen. Highly DiAcSpm-specific
antibodies were enriched from crude sera through a series of affinity-based
fractionations. A competitive ELISA system, intended for measuring DiAcSpm in
solution, was constructed using this antibody preparation, with N-acetylspermine
coupled to a synthetic peptide via N-(8-maleimidocapryloxy)-succinimide as a
solid phase antigen. The Ki value for DiAcSpm with this competitive ELISA system
was 33 nM, and the cross-reactivity with DiAcSpm, AcSpm, DiAcSpd, N1-AcSpd, and
N8-AcSpd was 100, 0.29, 0.20, 0.033, and 0.055%, respectively. This procedure can
be applied to the determination of DiAcSpm in human urine samples, giving highly
reproducible results. The coefficients of variation obtained were 6.7 and 4.2%
for within-run and between-run precision, respectively. The correlation
coefficient between DiAcSpm concentrations in urine estimated by ELISA and those
by HPLC analysis was calculated to be 0. 99, and the regression equation was
expressed as y = 1.04x + 0.026 microM.
PMID- 9644269
TI - Cholesteryl ester transfer protein reaction between plasma lipoproteins.
AB - The rate of the non-directional transfer of cholesteryl ester and triglyceride by
human cholesteryl ester transfer protein (CETP) was measured between human plasma
lipoproteins by monitoring fluorescence spectrum of pyrene-labeled lipid. The
transfer rates between high density lipoproteins (HDLs) and between low density
lipoproteins (LDLs) were both directly proportional to the substrate lipid
concentration within the physiological range of the lipoprotein concentration.
Higher preference of cholesteryl ester transfer to triglyceride was demonstrated
with HDL than LDL. Although the highly selective binding of CETP to HDL was
observed in the electrophoretic analysis, the transfer rate was only moderately
higher with HDL for cholesteryl ester and not so at all for triglyceride. In
addition, the rate of cholesteryl ester transfer between LDLs was uninfluenced by
the presence of a small amount of HDL that is just sufficient to absorb all the
CETP in the reaction mixture. The results indicated the preferential transfer of
cholesteryl ester over triglyceride by CETP in the interaction with HDL in non
directional lipid transfer reaction among lipoproteins. However, the apparent
binding of CETP to HDL does not seem to play an essential role in this type of
lipid transfer by CETP.
PMID- 9644271
TI - Bernstein's papers in motor control
PMID- 9644270
TI - Preparation of monoclonal antibodies against N-(gamma
maleimidobutyryloxy)succinimide (GMBS)-conjugated acetylspermine, and development
of an enzyme-linked immunosorbent assay (ELISA) for N1,N12-diacetylspermine.
AB - We have developed three mouse monoclonal antibodies (mAb) of types IgG1 and
IgG2b, i.e. anti-acetylspermine (Ac-Spm)-1 and 2 (ACSPM-1 and 2), and anti
acetylspermine (Ac-Spm)-3 (ACSPM-3), respectively, against Ac-Spm conjugated to
bovine serum albumin via a heterobifunctional cross-linker, N-(gamma
maleimidobutyryloxy)succinimide (GMBS). Among these mAbs, ACSPM-2 was the most
useful for the development of an enzyme-linked immunosorbent assay (ELISA) for
acetylpolyamines (Ac-PAs) with glutaraldehyde (GA)-conjugated N1,N12
diacetylspermine (2Ac-Spm) or acetylspermine (Ac-Spm) as the solid phase antigen.
However, GMBS-conjugated Ac-Spm did not behave as a solid phase antigen in the
competitive ELISA. The ELISA is based on the principle of competition between an
analyte and the conjugated antigen for the mAb, followed by immunoreaction with
biotinylated anti-mouse immunoglobulin and horseradish peroxidase-streptavidin.
The ACSPM-2 mAb reacted with 2Ac-Spm to the highest degree, followed by Ac-Spm,
N1-acetylspermidine (N1-Ac-Spd), N8,N8-diacetylspermidine (2Ac-Spd), and spermine
(Spm), the EC50 values being 0.06, 0.25, 7.0, 10, and 60 microM, respectively,
but exhibited almost no cross-reaction with other polyamine-related compounds or
amino acids. The method was used to determine the urinary Ac-PA levels in healthy
subjects, the average value of 0.36 microg of 2Ac-Spm/g creatinine (n = 16) being
obtained. The ACSPM-2 ELISA for 2Ac-Spm, which was the PA most relevant to the
analysis of human urine among the five PA analogs mentioned above, might have
potential for elucidation of the correlation of urinary 2Ac-Spm levels in
cancers.
PMID- 9644272
TI - Bernstein's last paper: the immediate tasks of neurophysiology in the light of
the modern theory of biological activity.
PMID- 9644273
TI - Rejecting the equilibrium-point hypothesis.
AB - The lambda version of the equilibrium-point (EP) hypothesis as developed by
Feldman and colleagues has been widely used and cited with insufficient critical
understanding. This article offers a small antidote to that lack. First, the
hypothesis implicitly, unrealistically assumes identical transformations of
lambda into muscle tension for antagonist muscles. Without that assumption, its
definitions of command variables R, C, and lambda are incompatible and an EP is
not defined exclusively by R nor is it unaffected by C. Second, the model assumes
unrealistic and unphysiological parameters for the damping properties of the
muscles and reflexes. Finally, the theory lacks rules for two of its three
command variables. A theory of movement should offer insight into why we make
movements the way we do and why we activate muscles in particular patterns. The
EP hypothesis offers no unique ideas that are helpful in addressing either of
these questions.
PMID- 9644274
TI - The structure of somatosensory information for human postural control.
AB - The goal of the present study was to determine the properties of the
somatosensory stimulus that alter its temporal coupling to body sway. Six
standing subjects were tested while touching a metal plate positioned either
directly in front of or lateral to the subject. In each condition, the plate
moved 4 mm at 0.2 Hz in either the medial-lateral (ML) or anterior-posterior
direction (AP). The results showed that coupling between body sway and touch
plate movement was strongest when the touch plate moved in a direction along the
longitudinal axis of the arm. Coupling strength was weaker when the touch plate
moved perpendicular to the longitudinal axis of the arm. The results consistently
show that a radial expansion stimulus was more effective than a lamellar-type
stimulus at the fingertip. Moreover, somatosensory information from a surface is
interpreted in terms of the orientation of the contact limb and the potential
degrees of freedom available through its movement.
PMID- 9644276
TI - The control of sequential goal-directed movement: learning to use feedback or
central planning?
AB - Fifteen participants practiced a two-target sequential aiming movement with
either full vision of the movement environment, vision during flight, or vision
while in contact with the first target. After 100 acquisition trials,
participants performed a retention test in their own condition and then were
transferred to each of the other two vision conditions. Both performance and
kinematic data indicated that rather than becoming less dependent on visual
information with practice, subjects learned to adjust their movement trajectories
to use the visual information available in their particular vision condition.
Although transfer to a degraded vision condition disrupted performance, when
vision was augmented participants quickly adjusted their aiming trajectories to
use the added information. The findings suggest that at least part of learning
involves the development of rapid and efficient procedures for processing
afferent information, including visual response-produced feedback.
PMID- 9644275
TI - Stability of rhythmic finger movement in children with a developmental
coordination disorder.
AB - The stability of single and bimanual (i.e., in-phase and antiphase) rhythmic
finger movements was studied in 24 children with a developmental coordination
disorder (DCD) and 24 matched controls from a dynamic pattern perspective.
Stability was assessed by applying perturbations and measuring the time the
system needed to return to its initial stability (i.e., the relaxation time). In
addition, fluctuations of the patterns were measured. For antiphase coordination
patterns, the frequency at which loss of stability occurred was also determined.
Children with DCD displayed less stable single and bimanual rhythmic coordination
patterns than control children. Further, within the DCD group, 9 children were
identified as having particularly poor bimanual coordination stability.
Individual differences suggested that variability of individual limb oscillations
might have contributed to this poorer interlimb coordination stability. Findings
were discussed in relation to a previous study on DCD in which the Wing
Kristofferson timekeeper model was applied.
PMID- 9644277
TI - Considering handedness in studies involving manual control.
AB - With studies of motor behavior that feature manual control, it is suggested that
the methodology used to select subjects in reference to handedness be reviewed.
This suggestion is in view of the recommendation that simply asking subjects to
identify their writing hand is inadequate to define handedness. Complementing
this are recent findings in neuroscience indicating differences, at times
significant, in information-processing behavior based on handedness
classification. A brief review of recently published studies in two prominent
outlets for motor behavior research confirms that most reports provide minimal
(and sometimes no) information regarding handedness and the method used for
assessment. Recommendations for addressing the problem include using an
acceptable preference inventory, selecting only those subjects with strong
lateral characteristics, and briefly describing the methodology used for the
reviewing audience.
PMID- 9644278
TI - Bernstein's rejection of Braune and fischer: studies on the physiology and
pathology of movements (1936).
PMID- 9644280
TI - Introduction to a special selection of research papers
PMID- 9644279
TI - Is dynamical systems modeling just curve fitting?
AB - The development of mathematical tools for describing dynamical systems has made
it possible to characterize forms of behavior that could not be characterized
before. This represents progress, but the enterprise runs the risk of being
nothing more than curve fitting if investigators fail to identify the physical,
biological, or psychological mechanisms which are common to systems that follow
the same dynamical regime and which are not common to systems that do not follow
the same dynamical regime.
PMID- 9644281
TI - Bimanual circle drawing during secondary task loading.
AB - Seven right-handed participants performed bimanual circling movements in either a
symmetrical or an asymmetrical coordination mode. Movements were paced with an
auditory metronome at predetermined frequencies corresponding to transition
frequency, where asymmetrical patterns became unstable, or at two-thirds
transition frequency where both symmetrical and asymmetrical patterns were
stable. The pacing tones were presented in either a high (1000 Hz) or low (500
Hz) pitch, and the percentage of high-pitched tones during a 20 s trial varied
between 0% and 70%. Participants were instructed to count the number of high
pitched pacing tones that occurred during a trial of bimanual circling. Overall,
the symmetrical pattern was more stable than the asymmetrical pattern at both
frequencies. Errors on the tone-counting task were significantly higher during
asymmetrical circling than symmetrical circling but only at the transition
movement frequency. The results suggest that cognitive processes play a role in
maintaining coordination patterns within regions of instability.
PMID- 9644282
TI - Fractioned reflex and reaction time in children with developmental coordination
disorder.
AB - The patellar tendon reflex (PTR) and simple visual reaction time (RT) were
fractionated and compared in 40 subjects with developmental coordination disorder
(DCD) and normal coordination (NC) in two age groups. Four equal groups of
subjects, 6 years DCD (6DCD), 6 years NC (6NC), 9 years DCD (9DCD), and 9 years
NC (9NC) were compared using ANOVA for the main effects of coordination and age.
PTR and its components of reflex latency and motor time were not significantly
affected by the level of coordination; however, a significant coordination by age
interaction (p < .05) revealed an increased motor time in the 6DCD group. RT,
premotor time, and motor time were all significantly (p < .05) increased in
children with DCD; the increased RT and premotor time support earlier findings,
whereas the increased motor time has not previously been found. These findings
suggest that the processing of reflexive and volitional responses by children
with DCD differs from that of their NC peers.
PMID- 9644283
TI - Provision of external cues and movement sequencing in Parkinson's disease.
AB - The basal ganglia (BG) may play a part in motor sequencing. Individuals with
Parkinson's disease (PD) may exhibit progressive slowing (sequence effect) during
motor sequences such as writing (micrographia) and gait. In the present study, a
serial two-way choice reaction time (CRT) task was employed, in which advance
information about each next movement was not provided until the participant began
moving, thereby assessing the participant's ability to utilize advance
information. Participants were 13 individuals with idiopathic PD and 13 age
matched controls. Both PD subjects and controls showed a significant sequence
effect in the absence of advance information, possibly reflecting difficulty in
initiating and maintaining movement without external cues. PD subjects and
controls both exhibited a sequence effect at moderate levels of advance
information. At high levels of advance information, PD subjects showed the effect
but controls did not, suggesting that controls, unlike PD subjects, were able to
use the extra information to facilitate performance, perhaps reflecting more
frontal aspects of impairment in PD.
PMID- 9644284
TI - Foreperiod length, but not memory, affects human reaction time in a precued,
delayed response.
AB - The effect of foreperiod length on reaction time in memorized (MM) and
nonmemorized (NM), precued, delayed responses was investigated. Six subjects
participated in one long and one short foreperiod schedule testing session. An
aiming task, using elbow supination/pronation, in response to a visual stimulus
was employed. In the MM condition, target spatial information was available for a
fraction of the foreperiod duration. In the NM condition, target information was
available continuously until the subject attained the target position. Subjects
responded with a significantly longer latency in the long foreperiod schedule.
Within each foreperiod schedule, the shortest foreperiod resulted in
significantly longer reaction time. However, the absolute value of foreperiod did
not have a major effect on reaction time latency. Memorization and
nonmemorization conditions did not affect reaction time.
PMID- 9644285
TI - Does having to remember the position of a target improve reaction time?
AB - In the monkey, reaction time in a precued delayed response task was found to be
faster when the animals had to remember the precue than when it was continually
available (Smyrnis, Taira, Ashe, & Georgopoulos, 1992). We investigated whether
this reflects a general principle that applies to all types of precued tasks.
However, we found the opposite result in a simpler task in humans. Our findings
suggest that the beneficial effect of a memory requirement on reaction time in
the monkey may reflect an effect of task difficulty, rather than a fundamental
process involved in all precued movement tasks.
PMID- 9644286
TI - Lip and tongue function in multiple sclerosis: A physiological analysis.
AB - A physiological analysis of the articulatory function of 16 adults with multiple
sclerosis (MS) was performed using lip and tongue transduction systems. Sixteen
nonneurologically impaired adults, matched for age, gender, and education, served
as controls. The MS speakers demonstrated patterns of tongue function that were
significantly different from those of the control speakers. Specifically, the MS
speakers were found to have significantly reduced tongue strength, endurance, and
rate of repetitive movements. In addition, preclinical signs of lingual
dysfunction were evident in nondysarthric MS speakers on endurance and rate tasks
when compared to control subjects. These physiological findings could account for
the perceptual findings of impaired articulation and reduced intelligibility. No
lip dysfunction was found on either the physiological or perceptual assessments.
PMID- 9644287
TI - Effect of oral levodopa treatment on articulatory function in Parkinson's
disease: preliminary results.
AB - To quantify lip function in 16 patients with Parkinson's disease, a computerized
semiconductor lip pressure transducer system was used prior to subjects being
administered oral levodopa and at approximately 0.5 hr, 1.5 hr, and 3.0 hr
postmedication. Two blood samples were taken from each subject at varying times
during the levodopa dosage interval, and the exact time and dosage of levodopa
were noted. Lip function measurements were expressed as percentage changes from
baseline and were plotted for each subject against time and levodopa
concentrations to determine the effects of levodopa therapy on articulatory
function. The results supported the effectiveness of levodopa therapy in
improving lip function. In particular, lip pressures recorded during both speech
and nonspeech tasks tended to improve after levodopa administration, the lip
measures improving somewhat in parallel with the rise and fall of blood plasma
levodopa concentrations. Evidence of a hysteresis effect was noted.
PMID- 9644288
TI - Bernstein's revolution in movement medicine: coordination disorders and the
recovery of walking biodynamics after cerebrovascular injuries (1954).
PMID- 9644289
TI - Recent tests of the equilibrium-point hypothesis (lambda model).
AB - The lambda model of the equilibrium-point hypothesis (Feldman & Levin, 1995) is
an approach to motor control which, like physics, is based on a logical system
coordinating empirical data. The model has gone through an interesting period. On
one hand, several nontrivial predictions of the model have been successfully
verified in recent studies. In addition, the explanatory and predictive capacity
of the model has been enhanced by its extension to multimuscle and multijoint
systems. On the other hand, claims have recently appeared suggesting that the
model should be abandoned. The present paper focuses on these claims and
concludes that they are unfounded. Much of the experimental data that have been
used to reject the model are actually consistent with it.
PMID- 9644290
TI - Intrinsic muscle properties facilitate locomotor control - a computer simulation
study.
AB - The purpose of this study was to investigate, theoretically, to what extent
muscle properties could contribute to recovery from perturbations during
locomotion. Four models with different actuator properties were created: the FLVT
model, which encompassed force-length (FL) and force-velocity (FV)
characteristics of human muscles as well as muscle stimulation inputs as
functions of time (T); the FLT model, which had muscles without force-velocity
characteristics; the FVT model, which had muscles without specific force-length
characteristics; and the MT model, which had no muscles but was driven by joint
moments (M) as a function of time. Each model was exposed to static and dynamic
perturbations and its response was examined. FLVT showed good resistance to both
static can dynamic perturbations. FLT was resistant to static perturbation but
could not counteract dynamic perturbation, whereas the opposite was found for
FVT. MT could not counteract either of the perturbations. Based on the results of
the simulations, skeletal muscle force-length-velocity properties, although
interactively complex, contribute substantially to the dynamic stability of the
musculoskeletal system.
PMID- 9644291
TI - Learning transfer from flexion to extension movements: importance of the final
position.
AB - Nine subjects (experimental group) were tested on rapid elbow flexion and
extension movements performed in the same final position, prior to and after
extensive practice of the movements. Nine additional subjects (control group)
were also tested, but without any practice between the tests. Comparison of the
pretest and posttest results suggested that the experimental group decreased
their variable error (i.e., standard deviation of the final movement position) in
both practiced (elbow flexion) and nonpracticed (elbow extension) movement. The
control group, however, did not improve in either of tested movements. The
experimental group demonstrated lower variable error in the nonpracticed elbow
extensions than the control group, while the same difference for practiced elbow
flexion movements was slightly below the significant level. The results support
the importance of the final position in programming of rapid, self-terminated
movements; however, they do not rule out the role of other kinetic and kinematic
variables (such as movement distance).
PMID- 9644292
TI - Relative coordination reconsidered: a stochastic account.
AB - Von Holst (1939/1973) parsed intersegmental coordination into relative and
absolute to distinguish moderate and extreme forms. Kelso and DeGuzman (1992)
discussed an interpretation of relative coordination in terms of the chaotic
phenomenon of intermittency. The data of concern (DeGuzman & Kelso, 1991) do
not, however, exclude a stochastic interpretation, which is detailed here
following earlier suggestions. The key difference is modeling relative
coordination by stochastic variability about weak attractors rather than by
deterministic variability about remnants of attractors ("ghost attractors"). The
intermittency interpretation is not robust in the presence of noise and,
therefore, is not well disposed to account for uncertainty in detailing a model
of behavioral data or its parameters. In contrast, the stochastic interpretation
is based upon an approximation of unknown underlying processes in the form of
Gaussian white noise. A stochastic method for estimating model parameters from a
stationary probability distribution and a mean first passage time is illustrated
using experimental and simulated data.
PMID- 9644293
TI - Facilitation of a hand muscle response to stimulation of the motor cortex
preceding a simple reaction task.
AB - Transcranial magnetic stimulation (TMS) of the motor cortex was used to produce
compound motor evoked potentials (cMEPs) in the first dorsal interosseus (FDI)
muscle. The size of cMEPs was measured as an index of corticospinal excitability
before and after initiation of a simple reaction task (SRT). The SRT, consisting
of an abduction of the right index finger against a vertical support in response
to a 1 kHz cueing tone, was performed in 6 healthy male subjects. cMEPs were
facilitated when timed to occur just before the fastest simple reaction time
(fSRT). When the cMEP was placed 15.5 +/- 1.5 ms before the fSRT, its amplitude
increased to 176 +/- 36% of the control response seen in the relaxed state (no
SRTs). Facilitation of the cMEP increased to 382 +/- 43% of the control when it
was placed 11.9 +/- 1.5 ms after the fSRT. The facilitation of cMEP responses
prior to the SRT is discussed with particular reference to the premovement
potential that may be recorded over the cortex prior to a voluntary movement.
PMID- 9644294
TI - Pointing to remembered targets in 3-D space in Parkinson's disease.
AB - A three-dimensional tracking system was used to examine whether subjects with
Parkinson's disease (PD) would show characteristic performance deficits in an
unconstrained pointing task. Five targets were presented in a pyramidal array in
space to 11 individuals with mild to moderate PD and 8 age-matched controls.
After the target was indicated, subjects closed their eyes and pointed to the
remembered target locations without vision. Despite the absence of visual
feedback during movement, PD subjects were as accurate overall as controls.
However, PD subjects showed greater variable errors, more irregular trajectories,
and a vertical endpoint bias in which their endpoints were significantly lower
than controls. They also showed deficiencies in the compensatory organization of
joint rotations to ensure consistency in azimuthal (horizontal) positioning of
the arm endpoint. We concluded that, under appropriate task conditions, PD
subjects may not show overall deficits in accuracy even when making targeting
movements at normal speed without visual feedback. Nevertheless, our findings
indicate that there are certain dimensions of performance which are selectively
altered in Parkinson's disease even when overall performance is normal.
PMID- 9644295
TI - Rare alteration of genomic structure or expression of the DPC4 gene in
myelogenous leukemias.
AB - We examined homozygous deletion, point mutation and expression of DPC4 gene, a
recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with
myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of
chronic myelogenous leukemia including 22 in the chronic phase, 3 in the
accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous
leukemia including 9 at the initial presentation and 10 at relapse. Polymerase
chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single
strand conformation polymorphism study for the entire coding region were carried
out. Homozygous deletion or subtle mutation was not detected in any of the
samples examined. However, 3 patients with various clinical phases showed a
decrease of DPC4 expression. These results suggest that DPC4 alteration is not a
crucial event in the development or the progression of myelogenous leukemias.
PMID- 9644296
TI - Pentoxifylline synergizes with all-trans retinoic acid to induce differentiation
of HL-60 myelocytic cells, but suppresses tRA-augmented clonal growth of normal
CFU-GM.
AB - All-trans retinoic acid (tRA) has been shown to promote terminal differentiation
of promyelocytic leukemia cells, but frequently induce hyperleukocytosis and
pulmonary leakage syndrome. Employing pentoxifylline (PTX), a phosphodiesterase
inhibitor which could raise intracellular cAMP and modulate leukocyte activation,
we sought to investigate if PTX could enhance tRA-induced promyelocytic leukemic
cell differentiation but suppress tRA-augmented growth and activation of human
granulocytes. tRA could significantly suppress clonal growth of U937 and HL-60
leukemic cells but enhanced the CFU-GM formation of normal bone marrow cells (22
+/- 6 vs. 90 +/- 16 CFU/well). PTX significantly augmented tRA suppression of
clonal growth of U937 and HL-60 leukemic cells but suppressed tRA-augmented CFU
GM formation of normal bone marrow cells (90 +/- 16 vs. 25 +/- 9 CFU/well). In
addition, PTX enhanced tRA-induced growth inhibition and differentiation of
promyelocytic HL-60 leukemic cells, but suppressed respiratory burst activation
by the immature granulocytic HL-60 cells and suppressed CD11b adhesion molecule
expression by mature granulocytes. PTX similar to dibutyric cAMP promoted HL-60
myelocytic leukemic cell differentiation and growth inhibition, whereas PTX, in
contrast to dibutyric cAMP which could augment phorbol myristate acetate (PMA)
elicited respiratory burst activity by immature granulocytes, suppressed the PMA
elicited respiratory burst activity by immature and mature granulocytes. PTX did
not raise the intracellular cAMP level of HL-60 cells, but partly suppressed the
dibutyric cAMP-elicited elevation of intracellular cAMP level. Results from these
studies suggest that PTX might act through different signaling pathways to
enhance tRA-induced myelocytic leukemic cell differentiation but prevent from
hyperreactive normal granulopoiesis and granulocyte activation.
PMID- 9644297
TI - Haematological effects of oral cobalamin preparations on patients with
megaloblastic anaemia.
AB - We investigated the haematological effects of a massive dose of oral cobalamin
(vitamin B12) on patients with cobalamin deficiency anaemia who had severe
anaemia with a few neurological impairments and found that oral treatment was
almost as effective as conventional injection therapy. The recovery of
haematological indices with oral cobalamin preparations was slightly slower than
with parenteral preparations, although the subjective symptoms disappeared soon
after the start of therapy. The results of this study indicate that oral
treatment keeps the cobalamin body stores satisfactorily filled and might be
useful for older patients in whom injecting might be difficult.
PMID- 9644298
TI - Effect of discontinuing prophylaxis with norfloxacin in patients with hematologic
malignancies and severe neutropenia. A matched case-control study of the effect
on infectious morbidity.
AB - The use of fluorinated quinolones for prophylaxis of infections in neutropenic
cancer patients has led to a reduction of infections with gram-negative enteric
bacilli, but there is concern about the emergence of antibiotic-resistant entero
bacterial infections and a rise of gram-positive bacteremias. Due to these
concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our
unit. In order to evaluate the impact of this measure on the infectious morbidity
in our unit, 91 severe neutropenic episodes in 58 patients with hematologic
malignancies who did not receive norfloxacin prophylaxis (NO group) were closely
matched to 91 episodes in 60 patients who received norfloxacin prophylaxis
(NORFLO group). There were no differences in the incidence of febrile
neutropenia, fever of unknown origin or bacteremia during the first febrile
episode. There was a trend for a higher rate of coagulase-negative staphylococcal
bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups,
respectively, p = NS). Enterobacterial bloodstream infections were more frequent
in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia
coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial
isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the
NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of
norfloxacin prophylaxis in our ward led to a rapid increase in the rate of
fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on
infectious morbidity. This suggests that the selection of resistant flora in an
inpatient ward by prophylactic antimicrobials may be reversible following the
discontinuation of the prophylactic agent(s).
PMID- 9644299
TI - Serum hyaluronan as a marker of liver fibrosis in hemophiliacs with hepatitis C
virus-associated chronic liver disease.
AB - We measured serum type III procollagen peptide, type IV collagen (IV-C), and
hyaluronan (HA) in 36 hemophiliacs with hepatitis C virus (HCV)-related chronic
liver disease. We also measured these markers in 19 interferon (IFN)-treated
patients before and after a 6-month course of IFN-alpha. The serum concentrations
of IV-C and HA were correlated with the stage of fibrosis (IV-C r = 0.38; HA r =
0.78). These markers fell only in complete responders showing sustained clearance
of serum HCV RNA by IFN. These results suggest that, in hemophiliacs with chronic
liver disease, serum HA measurement might be an alternative to liver biopsy and
reflect the response to IFN.
PMID- 9644300
TI - Autoimmune thrombocytopenia associated with hepatitis C virus infection.
AB - We have retrospectively analyzed a series of 19 patients with hepatitis C virus
(HCV) infection and chronic thrombocytopenia not attributable to hypersplenism or
to other causes. Antiplatelet antibodies were present in 81% of cases. Response
to prednisone was observed in 6 of 7 patients and 1 of 3 patients responded to
intravenous immunoglobulins. No case of reactivation of liver disease was
observed during or after therapy. We consider that the possibility of an
underlying mechanism should be evaluated in thrombocytopenic patients with HCV
infection who do not present hypersplenism. These patients could benefit from
steroid treatment.
PMID- 9644301
TI - Coexistence of chronic myelogenous leukemia and multiple myeloma. Case report and
review of the literature.
AB - A case report of simultaneous presentation of chronic myelogenous leukemia (CML)
and multiple myeloma (MM) in a 72-year-old female is described. Our case was
typical of Ph1-positive and chimeric bcr-abl messenger RNA-positive CML.
Furthermore, a marked IgG (kappa-type) paraproteinemia was present. Fluorescence
in situ hybridization showed that 97% of marrow nucleated cells were positive for
bcr-abl fusion signal, when myeloma cells in the bone marrow amounted to 19.0%.
In the literature survey, 4 similar cases with coexistence of CML and MM have
been identified.
PMID- 9644302
TI - Remission induction by granulocyte colony-stimulating factor in hypoplastic acute
myelogenous leukemia complicated by infection. A case report and review of the
literature.
AB - A patient with hypoplastic acute myelogenous leukemia (AML) who achieved
remission with granulocyte colony-stimulating factor (G-CSF) alone is reported.
The 59-year-old male patient received antibiotics and G-CSF but not any
antileukemic drugs because of ongoing pneumonia. After 2-week administration of G
CSF, he achieved complete remission and his pneumonia improved. Since leukemia
relapsed after 3 months, he received G-CSF again for 5 weeks, but failed to be in
remission this time. He underwent antileukemic chemotherapy and achieved second
remission. When he suffered from a second relapse after 7 months, intensive
chemotherapy was commenced but was stopped on the 2nd day since his general
condition became very poor due to septicemia. He began to receive G-CSF again and
achieved third complete remission after 3 weeks. In vitro studies showed that G
CSF did not stimulate proliferation of the patient's blast cells although they
expressed G-CSF receptor on their surface. Moreover, G-CSF induced
differentiation of the blast cells into segmented neutrophils in vitro. According
to the literature, in all of the 12 patients with AML who were reported to
achieve remission by G-CSF the course was complicated by infection, and 7 of the
patients were diagnosed as hypoplastic acute leukemia. It is suggested that not G
CSF alone but G-CSF with infection could induce remission, which might be related
to a differentiation effect of G-CSF in this case. G-CSF is not only safe but
also useful for remission induction therapy in hypoplastic acute leukemia.
PMID- 9644303
TI - Accelerated phase of chronic myeloid leukemia presenting with hypercalcemia and a
mediastinal mass.
AB - A patient with chronic myeloid leukemia developed hypercalcemia as a presenting
sign of the accelerated phase of the disease. Ultrasound of the neck showed a
large hypodense mass connected to the thyroid gland, which was thought to be a
parathyroid tumor and the cause of the hypercalcemia. Histology of the surgically
removed mass revealed a chloroma. The patient's course was complicated by
respiratory failure and metastatic calcinosis of the lung, an unusual finding in
hypercalcemia of short duration.
PMID- 9644304
TI - Reference values for bisphosphoglycerate mutase protein content and specific
activity in human erythrocytes.
PMID- 9644305
TI - Haemostasis, thrombosis, and endothelium in Behcet's disease.
PMID- 9644306
TI - [Recent progress of matrix metalloproteinase (MMP) research and its clinical
application for cancer therapy].
AB - The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound
zinc-endopeptidases. These enzymes are capable of degrading the extracellular
matrix, including collagens, laminin, proteoglycan and fibronectin. In some human
cancers, a positive correlation has been demonstrated between MMP expression and
the likelihood of developing metastasis. An imbalance between MMPs and the
tissues inhibitor of metalloproteinases (TIMPs) may play a significant role in
the invasive phenotype of cancers. Although TIMPs have been shown to inhibit
tumor metastasis in some in vivo models, they are not suitable for pharmacologic
applications due to their short half-life in vivo and large molecular size. In
this paper, recent advances in MMP research and reports of clinical applications
of synthetic MMP inhibitors for cancer patients are reviewed.
PMID- 9644308
TI - [Risk factors in aged patients undergoing gastrointestinal cancer operations].
AB - With the rapid increase in the elderly population in Japan and the continued
advances in perioperative management and operative techniques, more surgical
procedures will be performed in the geriatric patients. The loss of reserve
capacity and associated disease in the elderly patients may lead to an
inappropriate response to surgical stress, resulting in high morbidity and
mortality. Therefore, the identification of surgical risk is imperative in the
surgical care of aged patients. The risk factors in the aged include
malnutrition, anemia, cerebrovascular disease, hepatic disorders and
immunosuppressive therapy. This review focuses on the risk factors and simple
method to estimate the surgical risk in aged patients undergoing gastrointestinal
cancer surgery.
PMID- 9644309
TI - [Cancer chemotherapy in patients of advanced age (over 75)].
AB - Generally, elderly patients are excluded from therapeutic trials because of
decreased tolerance to chemotherapy. We discussed chemotherapy cancer patients of
an advanced age based on our experience of malignant lymphoma and advanced
gastric cancer patients over 75 years of age. We found the tendencies for
diagnosis at more advanced stages involved many complications, especially 10% of
cases have double cancer, and not good performance status in these patients. Some
53 cases of malignant lymphoma were treated with combination chemotherapy
including anthracycline, obtained prolongation of survival in responder. On the
other hand, 64 cases of advanced gastric cancer were treated with palliative
chemotherapy. Some clinical trials have showed that older and younger patients
were no different in terms of response, toxicity and overall survival. But these
selected elderly patients could be entered in clinical trials, seemed to have to
have surprisingly good health, no historical complications and good performance
status, in spite of suffering from cancer. Not only chronological age but also
the kinds of cancer and performance status are important justification for
decisions to limit or withhold treatment.
PMID- 9644310
TI - [Radiotherapy for elderly patients].
AB - Radiotherapy is of particular benefit to elderly patients as alternative surgery,
and it is widely used with curative and palliative intent. Patients aged 75 and
older accounted for 5-10% of all cases, and half of them had some complications.
Radical radiotherapy was performed in 63-73% of the elderly patients and 88-100%
were able to complete the planned course. Several authors reported that the
elderly patients adequately staged, can tolerate radical radiotherapy and have
survival comparable to that of younger patients. But careful management is
needed.
PMID- 9644311
TI - [Treatment of prostate cancer in patients aged 75 or older].
AB - In view of the increasing incidence and mortality rate of prostate cancer in
Japan, the management of elderly patients with prostate cancer is an important
issue now. We therefore analyzed the clinicopathological features and long-term
outcomes of 182 patients with prostate cancer, aged 75 or older, in order to
establish the treatment strategy for this age group of patients. There were more
patients with advanced disease (stage C-D) than those with localized disease
(stage A2-B), and the patients with moderate to poorly differentiated tumors were
more numerous than those with well-differentiated tumors. The overall survival
curve of the patients with localized prostate cancer was in line with the age
matched expected survival curve, while that with advanced prostate cancer was far
below the expected survival curve. These results demonstrated that advanced
prostate cancer in elderly patients is as harmful as in younger patients,
indicating the necessity for early detection and treatment of prostate cancer
among the younger generation. On the other hand, localized prostate cancer in
elderly patients should be treated less invasively to maintain their quality of
life.
PMID- 9644312
TI - [Treatment of gynecologic cancer in elderly patients].
AB - Due to the increasingly elderly population and prolonged life span of women in
Japan, population of women older than 75 years of age has become 7.3% of all
female population in 1995. According to this change, elderly patients with
gynecologic malignancies, such as cervical cancer, endometrial cancer and ovarian
cancer have increased markedly. Those patients tend to have progressed disease
and therefore treatments should be less invasive and tailored based upon
individual conditions to maintain their quality of life.
PMID- 9644313
TI - [Cancer chemotherapy in patients older than 75 years old--from the aspect of
clinical pharmacology].
AB - A review concerning cancer chemotherapy in older patients from the aspect of
clinical pharmacology was performed. Age-related physiological changes, comorbid
disease, polypharmacy, and social issues are major problems in older patients
with cancer. Pharmacokinetics of anticancer agents change according to
physiological changes, and distribution, metabolism and excretion may change.
Resistance to anticancer agents is more common. Side effects are more severe and
frequent because of age-related physiological changes and comorbid disease. Since
the interindividual difference is large in the elderly, the individual dose of
anticancer agents must be determined especially for patients older than 75 years
old.
PMID- 9644314
TI - [Phase II study of KRN8602 (MX2) for malignant lymphoma].
AB - We performed a clinical phase II study of KRN8602, a new anthracycline
derivative, for relapsed or recurrent malignant lymphoma. KRN8602 was given at
doses of 12-15 mg/m2 for 3 consecutive days, repeating every 3-4 weeks. Among 44
patients entered into the study, 36 were evaluable for safety, and 35 were
evaluable for efficacy. The response rate was 18.2% (6PR/33) for non-Hodgkin's
lymphoma and 0% (0/2) for Hodgkin's disease. Major toxicities were bone marrow
suppression and gastrointestinal toxicity. Leukopenia was observed in 77.8%,
thrombocytopenia in 44.4%, hemoglobin decrease in 44.4%, nausea and vomiting in
94.4% and anorexia in 80.6%. However, all toxicities were clinically manageable.
PMID- 9644315
TI - [Thymidylate synthase expression in patients with hypopharyngeal carcinoma].
AB - We analyzed the relationship between clinical response to neo-adjuvant
chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal
carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS
expression was evaluated with immunohistochemical staining techniques on biopsy
specimens from HPC patients. TS immunostaining was divided into four levels (TS0
TS3) according to its level and pattern. The relationship between prognosis,
tumor size, nodal status, differentiation of tumor cells and TS expression were
also investigated. There was a statistically significant association between the
level of TS expression and tumor size (p < 0.01). In terms of the effectiveness
of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical
difference was not found in TS expression. These results suggest that the level
of TS expression may show the degree of tumor proliferation, but may not
necessarily be useful to obtain a response to chemotherapy including other drugs,
e.g., cisplatin and other derivatives of platinum.
PMID- 9644316
TI - [Comparative study on quality of life between weekly and monthly chemotherapy
with cisplatin, vindesine and mitomycin C in patients with non-small cell lung
cancer].
AB - A comparative study between weekly and monthly chemotherapy with CDDP, VDS and
MMC was performed on the basis of QOL in patients (stage III A/III B/IV) with non
small lung cancer from September 1993 to August 1996. Arm A received CDDP (80
mg/m2) monthly on day 1, VDS (3 mg/m2) on days 1 and 8, MMC (8 mg/m2) on day 1.
Arm B received CDDP (40 mg/m2), VDS (3 mg/m2) and MMC (4 mg/m2) on day 1, and
followed by CDDP (20 mg/m2), VDS (1.5 mg/m2) and MMC (2 mg/m2) weekly. A diary
type QOL self-rating questionnaire was devised for this study, consisting of 5
scales including 13-item questionnaires and a face scale as the global scale.
Chronological QOL data from 20 days during chemotherapy (total dose of CDDP was
80 mg/m2 in both A and B arm) were analyzed using summary measures. In the 78
eligible subjects of the study, 34 were QOL subjects of the 27 eligible subjects,
13 were in arm A and 14 in arm B. 1. The questionnaire was confirmed to be
satisfactory with regard to reliability and validity as a questionnaire for the
evaluation of this study by factor and correlation analysis. 2. Although each
scale changed to the worth level after chemotherapy, there was no significant
difference between arm A and B. 3. Summary statistics were assessed using indices
of the area under the curve (AUC) and the maximum fluctuations of QOL scores (Dif
max) arm B showed a tendency to smaller changes than arm A in AUC and Dif max.
There was a significant difference in the physical well-being scale of Dif max.
4. Three items, including the physical well-being in arm B, revealed a better
score than those of arm A. Abdominal condition showed a significant difference
between the two arms. 5. No obvious difference in anti-cancer effectiveness was
found between arm A and B. Arm B showed a longer median survival, less nausea and
vomiting, leukopenia and thrombocytopenia compared with arm A. The above results
suggested that weekly chemotherapy is as effective, less toxic and shows less
influence against patients QOL than the conventional monthly chemotherapy in this
study.
PMID- 9644317
TI - [A cooperative study on concomitant with low-dose divided administration of
cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for
unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study
Group].
AB - For patients with unresectable gastric cancer registered between July 1994 and
September 1995, the following dosage regimen was examined: a drip infusion of
cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a
week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300
mg/m2/day for 21 days. The whole cycle was repeated again after 2-week
withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect
to histological classification, there was no difference in appearance of the
effect between the moderately differentiated type at 62.5% and the low
differentiated type at 42.9%. The cases which became resectable after the
administration included those in which the tumor disappeared completely in the
resected specimens. As adverse reactions encountered in the cases above Grade 3,
anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10,
5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin,
leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively,
while renal or liver dysfunction did not occur. This dosage regimen was
considered useful for unresectable advanced gastric cancer, although
myelosuppression should be watched carefully.
PMID- 9644318
TI - [Anticancer drug intraperitoneal chemotherapy using T-type reservoir sheet for
unresectable gastric cancer].
AB - T-type reservoir sheets (anti-adhesion sheets developed to prevent adhesions +
reservoir) were intraperitoneally implanted in 16 patients with unresectable
gastric cancer and postoperatively used to suction off ascitic fluid, to prevent
cancerous adhesions of the intestines, and to intraperitoneally infuse anticancer
drugs with a view to improving QOL and prolonging survival time. The results
showed that whereas all of the patients had been class V according to
intraoperative cytodiagnosis, postoperatively they were all class I-II and their
ascites had either completely or temporarily resolved. Performance status (PS)
improved in 14 patients (87.5%), and 14 patients (87.5%) were discharged.
According to the Cancer Body Cavity Efficacy Rating Criteria (Japan Society for
Cancer Therapy), CR was achieved in 10 cases, PR in 3 cases, NR in 3 cases, and
the mean home care rate was 45.4%. Mean survival time to date, February 1997, is
7.8 months, two patients are alive, and the longest survival time has been 22
months. This method facilitates suctioning of ascitic fluid. It prevents
irregular adhesions of the intestine, and protects against the development of
ileus. It enables repeated intraperitoneal administration of high concentrations
of anticancer drugs, uniformly, extensively, safely and easily. It facilitates
intraperitoneal cytodiagnosis, ascitic fluid sampling, and monitoring of the
efficacy of anticancer agents. The special features of this method are the high
percentage of patients residing at home and the ability to administer
intraperitoneal infusions of anticancer agents continually and repeatedly on an
outpatient basis.
PMID- 9644319
TI - [An early phase II clinical study of S-1 in patients with breast cancer. S-1
Cooperative Study Group (Breast Cancer Working Group)].
AB - An early phase II clinical study of S-1 in patients with advanced or recurrent
breast cancer was undertaken by a cooperative study group (Breast Cancer Working
Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg
(dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty
eight patients were enrolled, 27 were eligible for the study, and 25 were
evaluable for efficacy. Four complete responses and seven partial responses were
obtained, and the response rate was 40.7% (11/27) [ninety percent confidence
interval for this response was 26.7-56.4%]. The major adverse reactions observed
were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7%
(11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia
55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The
results suggested that the efficacy and safety of S-1 were effective against
advanced or recurrent breast cancer. The objective of study judged should be
investigated in a late phase II clinical study.
PMID- 9644320
TI - [Late phase II study of TAT-59 (miproxifene phospate) in advanced or recurrent
breast cancer patients (a double-blind comparative study with tamoxifen
citrate)].
AB - The efficacy and safety of TAT-59 (miproxifene phospate) were compared with
tamoxifen citrate (TAM) in ER-positive or ER-unknown patients with advanced or
recurrent breast cancer, using the double-blind method. TAT-59 and TAM were both
given 20 mg/body orally for over 12 weeks in daily doses. Eligible cases were 93
in the TAT-59 group and 102 patients in the TAM group. The response rate was
shown to be 30.1% (28/93) in the TAT-59 group and 26.5% (27/102) in the TAM
group. Statistical equivalence between both treatments was proven at 90%
confidence interval (-8.5% < or =, < or = 12.8%). Adverse reactions observed in
the patients receiving TAT-59 were hot flush, nausea and vomiting, sweating,
anorexia, abnormal values in liver function tests, and anemia, showing no
differences from the TAM group. Leukopenia (4.9%) and thrombopenia (2.9%)
reactions were found only in the TAM group. Two patients in the TAT-59 group and
three in the TAM group discontinued treatment due to adverse reactions. However,
these adverse reactions were reversible in both groups. In conclusion, TAT-59 was
showed comparable efficacy and safety with TAM in ER-positive or ER-unknown
patients with advanced or recurrent breast cancer.
PMID- 9644321
TI - [A case of adenoid cystic carcinoma in epipharynx which responded to radiation
and chemotherapy].
AB - A 45-year-old man visited our hospital complaining of a right hearing loss. The
head and neck examination was unremarkable except for right secretory otitis
media. Fiberoptic examination of the nose and the epipharynx revealed a mass.
Transnasal biopsy was performed and histologic analysis revealed adenoid cystic
carcinoma. Invasion of the sphenoid sinus was identified by MRI. He was treated
with FAR therapy (5-FU, Vit A, Radiation) and chemotherapy (intra-arterial
infusion of ADM). Severe side effects were not seen during treatment. After
treatment, the majority of the tumor mass disappeared on fiberoptic examination
and MRI. On repeat biopsy specimens, no cancer cells were found. The patient was
alive with no evidence of disease as of August 1997.
PMID- 9644322
TI - [A case of hepatocellular carcinoma with reduction of primary tumor and
disappearance of multiple lung metastasis].
AB - A 56-year-old male had suffered from hepatocellular carcinoma treated by
operation, PHoT and TAE since 1994. In December 1995, he had multiple metastases
of lung in addition to recurrence of primary hepatic lesions. We discontinued
treatment of TAE and decided to administer UFT (400 mg/day) orally as an
outpatient. After seven months, the primary hepatic lesions were decreased in
size, and metastatic lesions of lung were completely eliminated with reduction of
AFP level. Generally, hepatocellular carcinoma with metastasis is refractory to
treatment. However, this result suggests that UFT is one of the effective
treatments for such advanced cases as having lung metastasis.
PMID- 9644323
TI - [Complete disappearance of metastatic pulmonary tumors in a case of
hepatocellular carcinoma treated with UFT].
AB - The disappearance of multiple pulmonary metastatic lesions in hepatocellular
carcinoma patient following the oral administration of UFT is reported. Pulmonary
and pelvic metastases were detected in a 71-year-old female hepatocellular
carcinoma patient treated by TAE (Trans-Arterial Embolization with epirubicin,
mitomycin C, lipiodol and Gelform) three times in one year. Four months after
beginning oral administration of UFT-E granule 1.5 g/day (tegafur 300 mg/day,
uracil 672 mg/day), three pulmonary metastatic lesions markedly reduced in size,
and disappeared completely 6 months after beginning UFT. A pelvic metastatic
tumor markedly reduced in size by the combined effect of radiation, TAE
(epirubicin, mitomycin C, lipiodol, Gelform) and oral UFT. We consider UFT was
effective in the disappearance of multiple pulmonary metastatic lesions, because
three TAE administrations of epirubicin and mitomycin C could not prevent
systemic spreading of hepatocellular carcinoma.
PMID- 9644324
TI - [A case of renal pelvic cancer with recurrence of liver metastasis showing
partial response by injection of methotrexate and intraarterial infusion of
cisplatin and pirarubicin].
AB - The patient was a 71-year-old man who had been diagnosed as having a left renal
pelvic cancer with liver metastasis. We performed total left nephroureterectomy
with lymphnode cleaning and partial resection of the liver. Because abdominal CT
5 months after the operation revealed multiple metastasis of the liver, we
performed chemotherapy with a regimen consisting of methotrexate 50 mg
(intravenous injection), cisplatin 30 mg and pirarubicin 20 mg (intraarterial
infusion), and leucovorin 3 mg (intramuscular injection), three times at
intervals of 6 hours. Ten days after chemotherapy, CT revealed the disappearance
of most of the liver metastatic lesions, and a partial response was obtained. We
are now performing the regimen at an interval of a month to a month and one-half
to control the metastatic lesions.
PMID- 9644325
TI - [Experimental study of intraperitoneal hyperthermic chemotherapy].
PMID- 9644326
TI - [Proposals for revisions of UICC TNM system (1997)--breast cancer].
AB - The TNM system for classification and staging approved by Union Internationale
contro le Cancer (UICC)/TNM Committee is designed primarily for patient care and,
in this context, is equally applicable to patients in clinical research,
community hospitals, and developing countries. It is clearly evident to all who
have been involved that international agreement on the classification of cancer
at all anatomical sites is exhilarating, since data from around the world can
finally be compared with validity. The UICC believes that the TNM system can
fulfil the following five objectives: (1) aid in the planning of treatment; (2)
give an indication of prognosis; (3) assist in evaluation of the results of
treatment; (4) facilitate the exchange of information between centres; and (5)
contribute to the continuing investigation of human cancer. The important
questions for planning of treatment (1), however, can not be answered by the
information of the clinical TNM stage as the concept in the Japanese Joint
Committee. The knowledge of the TNM stage does not yield information of
prognostic importance (2). More accurate indices of prognosis can be calculated
from multivariate analysis to examine many clinicopathological variables, and
biological markers along with patient age and nodal status. The analysis makes
the difficulties for the results of treatment due to the large number of
combinations with T and N subgroups (3) (4). According to the fifth objective (5)
of TNM classification, we would like to propose a more simple and pragmatic
classification by classifying patients into those requiring surgical approach and
adjuvant therapy.
PMID- 9644327
TI - Reactive oxygen species and silica-induced carcinogenesis.
AB - Although silica has recently been designated as a carcinogen, its mechanism of
carcinogenesis is not fully understood. Recent studies suggest that free-radical
reactions may play an important role in the initiation and progression of cancer.
This article summarizes literature on the generation of reactive oxygen species
(ROS) directly from silica and from silica-stimulated cells. It also summarizes
information concerning the role of ROS in silica-induced DNA damage as well as in
silica-induced cell proliferation, including the effects of silica on the
activation of nuclear transcription factors, induction of growth factors and
oncogene expression, redox regulation of the p53 tumor suppressor gene, induction
of apoptosis, and division of damaged cells. Understanding the role of ROS in
silica-mediated reactions may help develop therapeutic agents to block silica
induced free radical reactions and thus prevent or attenuate silica-induced
carcinogenesis.
PMID- 9644328
TI - Developmental and reproductive toxicity of inorganic arsenic: animal studies and
human concerns.
AB - Information on the reproductive and developmental toxicity of inorganic arsenic
is available primarily from studies in animals using arsenite and arsenate salts
and arsenic trioxide. Inorganic arsenic has been extensively studied as a
teratogen in animals. Data from animal studies demonstrate that arsenic can
produce developmental toxicity, including malformation, death, and growth
retardation, in four species (hamsters, mice, rats, rabbits). A characteristic
pattern of malformations is produced, and the developmental toxicity effects are
dependent on dose, route, and the day of gestation when exposure occurs. Studies
with gavage and diet administration indicate that death and growth retardation
are produced by oral arsenic exposure. Arsenic is readily transferred to the
fetus and produces developmental toxicity in embryo culture. Animal studies have
not identified an effect of arsenic on fertility in males or females. When
females were dosed chronically for periods that included pregnancy, the primary
effect of arsenic on reproduction was a dose-dependent increase in conceptus
mortality and in postnatal growth retardation. Human data are limited to a few
studies of populations exposed to arsenic from drinking water or from working at
or living near smelters. Associations with spontaneous abortion and stillbirth
have been reported in more than one of these studies, but interpretation of these
studies is complicated because study populations were exposed to multiple
chemicals. Thus, animal studies suggest that environmental arsenic exposures are
primarily a risk to the developing fetus. In order to understand the implications
for humans, attention must be given to comparative pharmacokinetics and
metabolism, likely exposure scenarios, possible mechanisms of action, and the
potential role of arsenic as an essential nutrient.
PMID- 9644329
TI - Influence of caloric intake on aging and on the response to stressors.
AB - Reducing the food intake of rodents to well below that of ad libitum fed animals
increases the life span. This action, which gerontologists often refer to as the
antiaging action of dietary restriction (DR), is due to the slowing of the aging
processes. DR also maintains most physiological processes in a youthful state and
delays the occurrence and/or slows the progression of age-associated disease
processes. This antiaging action of DR results from the reduced intake of
calories. Reduction of the body fat content does not play a causal role in the
antiaging action of DR, nor does reduction in the metabolic rate. Alterations in
the characteristics of carbohydrate metabolism and of oxidative metabolism in
response to DR have been found that are of such a nature that they could, at
least in part, underlie the antiaging action. Several theories have recently been
proposed in regard to the mechanisms responsible for the antiaging action of DR,
but none has been tested by rigorously designed studies. Of these theories, the
one that seems most promising is based on the fact that DR protects rats and mice
of all ages against the damaging actions of acute stressors. This protective
action against stressors may play a major role in the antiaging action of DR.
PMID- 9644330
TI - Improving the U.S. EPA Toxic Release Inventory database for environmental health
research.
AB - In 1986, Congress passed the Emergency Planning and Community Right-to-Know Act
(EPCRA) in response to the tragic death of thousands of people in Bhopal, India,
following the accidental release of the toxic gas methyl isocyanate (MIC) from a
Union Carbide facility. As a component of EPCRA, certain manufacturers are
required to report annually the total mass (pounds per year, lb/yr) of toxic
chemicals released into the environment (air, water, land, or underground
injection), treated on-site, or shipped off-site for further waste treatment.
This information is compiled by the U.S. Environmental Protection Agency (EPA)
into a publicly accessible database known as the Toxic Release Inventory (TRI).
The TRI database is designed to encourage pollution prevention and waste
reduction by increasing public access to and knowledge of environmental chemical
releases. EPCRA has been generally considered by industry, government, and
community representatives as one of the most successful environmental laws in
U.S. history. Over the past few years, EPA has initiated a three-phased expansion
to EPCRA reporting requirements that will enhance the overall usefulness of the
TRI database. The focus of this article is to discuss these changes and highlight
several current uses of the TRI database in environmental health research.
PMID- 9644331
TI - Nurse practitioners.
PMID- 9644332
TI - Chemoprophylaxis.
PMID- 9644333
TI - To have and to hold: nursing information in the 1990s and beyond.
AB - Within contemporary nursing a tension exists between the need to develop nursing
related databases, and the philosophical underpinning of current nursing care.
The arguments 'for' include the need to counteract the substitution of nurses by
care attendants, the move towards evidence-based practice, and an increasing use
of information technology in health care. Arguments against include the
philosophies of holism, the reliance of nurse clinicians on verbal communication,
the complexity of nursing data, and cumbersome nature of contemporary information
systems. In a healthcare context where the value of nursing must be demonstrated,
nurses will need to explore avenues that capitalise on the benefits offered by
the establishment of nursing specific data bases, without compromising the
preferred standard of nursing care. It is timely that contemporary activities
designed to establish common nursing data sets be reviewed. Nursing minimum data
sets, unified nursing languages, and more recent approaches including natural
language systems, conceptual graphs, multi-axial taxonomies and multi media
interfaces, make up an often confusing potpourri of approaches. The intention of
this paper is to provide explanations and examples of each approach in an effort
to reduce confusion and stimulate further debate.
PMID- 9644334
TI - "I want my mummy". Changes in the care of children in hospital.
AB - The Welfare of Sick Children in Hospital' was the formal title of a report
published in Britain in 1959 which came to be known as the Platt Report, after
Sir Harry Platt, the chairman of the parliamentary committee which investigated
the care of children in hospital. The committee found the hospitals were
miserable places for children, where they were expected to conform to ward
routines, not allowed to play; where to lie quietly was the accepted norm, and
where, under no circumstances, were the parents allowed to visit outside the
declared visiting hours. Subsequent to the publication of the Platt Report a
revolution occurred in children's hospitals in Britain and other western
countries, including Australia. This paper explores these changes, and discusses
implications for paediatric care in hospitals and paediatric nursing education
today.
PMID- 9644335
TI - Tracing the tax maze.
PMID- 9644336
TI - The female factory at Parramatta 1804-1850s.
AB - In the first few decades following the arrival of the First Fleet in 1788 there
came to be established three institutions in the young colony referred to as
female factories. The first was established at Parramatta in 1804 (Schultz, 1991:
4, 11-13) and the other two in 1827, one in Hobart (Schultz, 1991:32, 69) and the
other in Moreton Bay (Schultz, 1991:41). This is a brief account of the salient
features in the development of the first female factory which highlights the
status of women in that early society. In preparing the account I have drawn
heavily on Schultz's 'A Tapestry of Service' and Salt's 'These Outcast Women.'
PMID- 9644337
TI - Changing technology in health: product liability.
AB - Greater health consumer awareness and increasing levels of concern for the rights
of patients have led to patient care technology being more strictly regulated.
This article analyses both the general law issues and the particular statutes
that will be of relevance to those involved in evaluating and implementing such
technologies. There are three main elements to this analysis. Firstly, there is
the issue of liability for a product fault, which will in many cases be directed
by legislation back to the manufacturer of the goods. Secondly, those involved in
placement of patient care technology should be aware of anti-discrimination
legislation when making placement decisions. Finally, occupational health and
safety legislation sets minimum standards for technology used in healthcare
facilities. The author suggests ways of complying with the laws for each
regulatory regime.
PMID- 9644338
TI - Theoretical perspectives on narrative inquiry.
AB - Narrative inquiry is gaining momentum in the field of nursing. As a research
approach it does not have any single heritage of methodology and its
practitioners draw upon diverse sources of influence. Central to all narrative
inquiry however, is attention to the potential of stories to give meaning to
people's lives, and the treatment of data as stories. This is the first of two
papers on the topic and addresses the theoretical influences upon a particular
narrative inquiry into nursing scholars and scholarship. The second paper,
Conducting a narrative analysis, describes the actual narrative analysis as it
was conducted in this same study. Together, the papers provide sufficient detail
for others wishing to pursue a similar approach to do so, or to develop the ideas
and procedures according to their own way of thinking. Within this first
theoretical paper, perspectives from Jerome Bruner (1987) and Wade Roof (1993)
are outlined. These relate especially to the notion of stories as 'imaginative
constructions' and as 'cultural narratives' and as such, highlight the profound
importance of stories as being individually and culturally meaningful. As well,
perspectives on narrative inquiry from nursing literature are highlighted.
Narrative inquiry in this instance lies within the broader context of
phenomenology.
PMID- 9644339
TI - The art of poster presentation.
AB - Need to attract attention with a captivating poster? This article provides
helpful suggestions for the design and production of a poster. Layout, colour,
balance, lettering and the use of pictures are considered. Details are also
provided of the Research-poster Appraisal Tool (R-PAT) developed by Bushy (1991).
The authors recommend that poster presenters use the tool to self-assess
effectiveness prior to presentation. The tool can also be used by conference
organisers for rating displayed posters.
PMID- 9644341
TI - Web-site review: rural health.
PMID- 9644340
TI - Legionellae.
AB - Legionellae cannot be eradicated from the water supply, since they are naturally
occurring and ubiquitous. Routine bacteriologic culturing of man made aquatic
environments is not recommended (Soule et al 1995). Therefore any water use that
results in production of aerosols should be regularly evaluated to ensure the
source has not been contaminated with the bacteria. Any aerosolised water
entering a sterile area such as the lungs should be sterile. Tap water should not
be used to rinse any respiratory therapy equipment. Routine maintenance of water
supplies to eliminate sediment and scale from tanks and trays is essential
(Benenson 1995, Lowry & Tompkins 1993). Australian & New Zealand Standard AS/NZ
3666-1995 Parts 1 and 2 outline these requirements.
PMID- 9644342
TI - Megan Jane Johnstone.
PMID- 9644343
TI - Historical development of outcomes-based care delivery.
AB - Outcomes-based care delivery is both a subtle and profound change in practice. It
is proactive, patient-centered, data-generating, and establishes clear
accountability. Most importantly, outcomes defined and managed at the patient
provider level will be the quality conscience as health care enters a new
millennium.
PMID- 9644344
TI - The Vanderbilt model of outcomes management.
PMID- 9644345
TI - The clinical resource management model.
AB - The clinical resource management model is a highly successful method of
redesigning operations to focus on reducing costs while improving quality. In
these dynamic days in our medical centers it is important to maintain quality
standards while implementing cost reductions. Through careful analysis of our
practice we can learn from our best practicing providers and build systems to
replicate their example. By improving our processes of care we meet the
expectation of the public and our regulators through process improvement in a
collaborative, multidisciplinary manner.
PMID- 9644346
TI - Longitudinal outcomes measurement and management. Standardized practices across
the continuum of care.
AB - Longitudinal outcomes measurement involves collection of outcomes data across a
continuum of care services in a patient cohort. Measurement and management of
intermediate outcomes, within the varied care settings represented by the
continuum, must precede measurement of long-term outcomes to provide meaningful
information to providers. Once connected across a continuum of services,
longitudinal outcomes measures produce powerful findings that may be used to
successfully optimize the health care experience for patients and their families.
The postacute continuum is ripe with research opportunities and should be pursued
with vigor by outcomes researchers interested in understanding the contributions
of this segment of the continuum to the production of patient outcomes.
PMID- 9644347
TI - The concept and the development of chest pain emergency departments as a strategy
in the war against heart attack.
AB - Critical nurses in the CPED can have a very fulfilling role in expanding their
influence within the hospital setting, as well as within the community to become
part of the needed change to significantly reduce deaths from MI in the United
States. The mission impossible becomes possible when critical care nurses are
part of this challenging process. Nowhere can these efforts be better started
than in emergency department committed to continuous quality improvement changes
under this new paradigm. The person who can best help make this strategy work the
best is the critical care nurse in charge.
PMID- 9644348
TI - Outcomes management for interventional cardiology.
AB - In the evolution of quality assessment activities in interventional cardiology,
outcomes management has become the benchmark for demonstrating optimal care. The
high volume of interventional cardiology procedures performed each year mandates
that efficient, high-quality and cost-effective patient care be delivered to all
patients with cardiovascular disease. Although the interventional cardiology
procedures represent only a snap shot of the patient's management of coronary
artery disease, a long-term plan for positive outcomes is required. A
multidisciplinary approach to outcomes management facilitates institutions to be
competitive in today's health care market.
PMID- 9644349
TI - Port-access cardiac surgery protocols and early outcomes.
AB - As a new cardiac surgical procedure, port-access holds promise to significantly
impact the surgical approaches for treatment of CAD. Supporting collaborative
practice protocols contributes to early extubation, rapid in-hospital recovery,
and shortened LOS. Discharge protocols address postoperative concerns. Early
results suggest that patient recovery is shorter than the time for conventional
procedures; patients are able to return to an active lifestyle that is beneficial
to families, patients, and employers.
PMID- 9644350
TI - Impact of a critical care pathway for unstable mechanically ventilated patients.
PMID- 9644351
TI - The long-term mechanically ventilated patient. An outcomes management approach.
AB - As noted previously, prior to permanently instituting an outcomes approach, we
compared the effects of such a model to a nonoutcomes-managed approach. The
positive trend noted during the study interval has been sustained 2 years later,
and the variables of cost, LOS, and ventilator duration (median = 9 days for DRG
475, 483 combined) for these patients continue to be favorably affected (see
Figure 2). In addition, the outcomes-management model has been well accepted by
all members of the health care team. The outcomes manager is a respected and
valued member of the team and is central to the ongoing success of the approach.
Although the clinical pathway is an essential tool for focusing and delineating
multidisciplinary best-practice, the pathway (and processes of care contained
within) must be continually evaluated and changed as needed. The pathway cannot
be static if care is to be progressive. Essential to the process is a method of
collecting and processing data in a timely way. Further, it is important that
data collection, while important, not be the focus of the role of outcomes
manager. Instead, the focus is the delivery of timely and effective care. Our
current outcomes model applies to management of patients beyond the boundaries of
the MICU or pulmonary suite. In other words, once weaned and transferred to a
regular floor the outcomes manager no longer manages the patients (although she
does track selected outcomes). Management of patients throughout hospitalization
is a future goal, but we are convinced that this cannot be accomplished by a
single outcomes manager. Although we are aware that other outcomes models do
follow patients throughout the continuum of hospitalization and beyond, our
highly clinically interactive model precludes that possibility. We are currently
considering other similar unit-based positions to provide the desired continuity
following discharge from the MICU or pulmonary suite. Despite our enthusiasm for
the outcomes-management model, we recognize that other models may also result in
comparable, favorable outcomes. It is important that those who adopt similar
models of care delivery for managing patients requiring prolonged ventilation be
scientific in their approach. Long-term studies of the efficacy of these models
are essential if we are to truly provide quality care for our patients in the
future. Unfortunately, as noted earlier, bias will be hard to overcome. Hospitals
vested in rapidly establishing a stable financial bottom-line are likely to
embrace quick applications. Projects with a true experimental design to evaluate
efficacy, such as this one, will be rare in these organizations. Finally, it is
critical that variables of interest be inclusive of specific quality indicators
such as ventilator duration and complications rather than global institutional
markers such as LOS. Standardization of variables of interest is imperative if
outcomes are to be compared. For example, patients requiring long-term mechanical
ventilation are identified by the AACN's Third National Study Group on weaning as
those who require mechanical ventilation for more than 3 days. If we are to
compare other variables of interest such as total ventilator duration, such as
definition is essential or we will be comparing apples and oranges in the future.
Provision of quality, cost-effective care for patients requiring prolonged
ventilation is a true clinical challenge. Outcomes management is a
multidisciplinary method of care delivery that is systematic and comprehensive in
approach. Although little science exists related to the application of the model
for patients requiring prolonged ventilation, preliminary reports are promising
and warrant future applications and evaluation of the same.
PMID- 9644352
TI - Outcomes management for stroke patients using thrombolytics.
AB - In the current health care market, there is a sharp awareness by both consumers
and managed care providers that hospitals are only as good as the outcomes they
can produce. Collaboration among disciplines that provide services, in this case
treatment for stroke has enhanced patient outcomes. The synergy that has
developed among those involved has thus far created a win-win situation. The key
to successful outcomes is to have all those involved possessing a clear picture
of their role, accepting it, and taking ownership of it.
PMID- 9644353
TI - Impact of technology on costs and patient outcome.
AB - Technology is only as effective as the clinicians who employ the technology and
the system in which they function. For any technology to change patient outcome,
or be cost effective, clinicians must be educated and incented to change their
practice. At this point in American health care, technology appears to vary
widely in the effectiveness in which it is employed. Research consistently
decries the lack of effective use of technology. Some authors have claimed this
lack of consistent use of technology is near a crisis proportion, both in terms
of the costs and impact on patient outcome. The wide variability in technology
application is understandable owing to the lack of a unifying approach to the
application, education, and evaluation of technology. Only when we have an
organized system, lead by professional societies, will technology usage achieve
standardization. Until that time, individual hospitals need to follow guidelines
like the ones presented in this article to ensure patients are receiving optimal
and cost-effective care.
PMID- 9644354
TI - Integration of acute care CNS and case manager roles.
AB - To be effective in the new environment of managed health care, APNs must have a
transformed outlook on providing nursing care. Accountability for day to day care
that leads to shorter hospital stays and at the same time improves the quality of
care is essential. The nurse's focus can no longer be on each small piece of
care, but rather on a broad perspective of the entire continuum of care. The
expert skills of the critical care CNS are still needed to manage the complex
care required of patients in this setting. However, their focus needs to be
broadened so that the larger picture remains in sight. Coordination of the
activities of multiple care providers to achieve the ultimate goal of providing
cost effective, quality care will be a primary responsibility of the CNS-NCM.
This transition requires new thinking. Educational programs that include
perspective transformation are needed for CNS role transition to become expert in
the NCM role.
PMID- 9644355
TI - Patient advocacy through outcomes management. A cardiac surgery example.
AB - As we attempt to survive market forces that dominate the health care environment
today, nurses must be active participants in finding solutions that improve
patient care in a cost-effective manner. In our quest to reduce costs, however,
health care providers know first-hand that good patient care is cheaper than bad,
with its accompanying complications and readmissions. At our workplace, through
our professional organizations, and from our political activities, nurses must
offer a loud and unified voice towards the pursuit of patient-focused care.
Practices such as early extubation and blood conservation are not only cost
effective, they are clearly "the right thing to do."
PMID- 9644356
TI - Volume lung reduction surgery: a review.
AB - Emphysema, along with other chronic obstructive lung diseases, affects 13.5
million Americans and is the fastest-growing cause of morbidity and mortality in
the United States. Despite excellent medical management, there are many patients
who become unresponsive to therapy. The current surgical options include lung
transplantation and lung volume reduction surgery. It is important for nurses to
be current with these new surgical techniques. This article reviews the current
surgical procedure, postoperative complications, and patient outcomes.
PMID- 9644357
TI - Managing latex allergy in the cardiac surgical patient.
AB - Latex allergy affects about 1% of the general population and between 10% and 17%
of health care workers. The severity of a latex allergic reaction can range from
contact dermatitis to anaphylaxis and death. Critical care personnel must be able
to identify cardiac surgical patients at risk for a latex allergy and supply
alternative equipment, and medication. In addition, knowledge and provision of
emergency treatment of a Type I latex reaction is paramount. Critical care staff
need to educate both the patient and the family about latex allergy, including
latex allergy testing and community resources.
PMID- 9644358
TI - Minimally invasive cardiac surgery: a new frontier.
AB - Modern cardiac surgery has been based on cardiopulmonary bypass, myocardial
protection, aortic cross-clamping, and median sternotomy. Coronary artery bypass
graft (CABG) has proven to be an effective treatment for patients who require
surgical revascularization of the myocardium. Reports regarding the systemic
effects of cardiopulmonary bypass abound in the literature. Such effects include
hematologic, metabolic, pulmonary, cardiac, and cognitive dysfunction. Less
invasive procedures have initiated a dramatic shift in treatment paradigms as
well as reducing the cost of treatment. This article will discuss the MIDCAB--its
history, a description of the surgical procedure, indications for use and patient
selection, advantages and a perioperative plan including patient education and
physical assessment.
PMID- 9644359
TI - Technology utilization in the cardiac surgical patient: SvO2 and capnography
monitoring.
AB - Technology utilization in the cardiac surgical patient has proliferated, despite
a lack of evidence that the technology has a positive impact on patient outcomes.
Hospitals are left to their own efforts in deciding how and what technology to
use. The result is an inconsistent use of technology. The use of structured
guidelines can help hospitals improve the use of technology. Two controversial
technologies, capnography and mixed venous oxygen saturation monitoring, are
analyzed using this approach. It is essential for hospitals to support clinicians
as they use methods in the evaluation and implementation of technology.
Technology alone will not improve patient outcome or control costs.
PMID- 9644360
TI - Minimally invasive cardiac valve surgery.
AB - With the recent advancement and experience in minimally invasive coronary artery
bypass surgery in selected patients, minimally invasive valve surgery using
similar techniques is promising. Coupled with the movement in cardiac surgery to
decrease costs, hospital lengths of stay and recovery time, minimally invasive
techniques for both mitral and aortic valve surgery are promptly being pursued.
This article reviews various minimally invasive surgical techniques for mitral
and aortic valve surgery. Mitral valve surgery by means of port-access technology
is detailed. Techniques for minimally invasive aortic valve surgery via a
ministernotomy and a parasternal incision are described.
PMID- 9644361
TI - Transmyocardial revascularization surgery.
AB - Transmyocardial revascularization (TMR) surgery is a palliative and investigative
surgical procedure with the goal of increasing the quality of life for patients
with intractable angina pectoris who are unsuitable for percutaneous transluminal
coronary angioplasty or coronary artery bypass graft surgery. It improves
myocardial perfusion and oxygen supply to the left ventricle, thus decreasing the
frequency and intensity of anginal episodes. Many patients continue to have
episodes of angina post-operatively but the frequency of those episodes should
decrease. TMR may be a good treatment option for otherwise untreatable patients
who live with severe, debilitating angina.
PMID- 9644362
TI - Perceived and unmet needs of critical care family members.
AB - Family members of patients in the intensive care unit (ICU) may experience
stress, disorganization, and helplessness which may ultimately result in
difficulty in mobilizing appropriate coping resources, thus leading to anxiety.
The needs of family members are varied, and critical care nurses must become
attuned to these needs and acquire the skills to direct their interventions more
appropriately. This article presents the findings from a study that assessed the
perceived level of importance of the needs of family members during the first 18
to 24 hours after admission to the ICU using the Critical care Family Needs
Inventory. The study identified which needs were perceived as being met or unmet
by the family members using the Needs Met Inventory after 36 to 48 hours had
elapsed.
PMID- 9644363
TI - Reducing costs and improving processes for the interventional cardiology patient.
AB - The cardiology unit at the University of Chicago Hospitals developed a cost
saving mechanism in the care of postinterventional cardiology patients, reducing
time spent in the coronary care unit. Increased nursing education and training
and better identification of patient outcomes made this collaborative effort a
cost-saving and effective pilot.
PMID- 9644364
TI - Aggressive implementation of advance directives.
AB - Economic, social, and technical factors are an impetus for expressing end-of-life
decisions as advance directives. Despite opportunities, nurses do not appear to
be widely involved in practice and research regarding advance directives. Through
an extensive literature review, this article will discuss a historical
background, definitions of advance directives, positive outcomes, and several
barriers to completion. Critical care nurses and advance practice nurses play a
key role in educating nurses, their patients, and physicians about advance
directives. The use of advance directives will likely increase if nurses can
aggressively implement a plan on their unit. Specific methods of implementation
are explored.
PMID- 9644365
TI - Home care and the elderly.
PMID- 9644366
TI - Autonomy and the cognitively impaired elder.
PMID- 9644367
TI - Sleep disorders.
AB - Many clients have trouble battling afternoon fatigue, falling asleep, staying
asleep, or having a restful night's sleep. Approximately 33% of the adult U.S.
population--about 65 million people--suffer from sleep disorders. One of two
people have experienced insomnia. At least 10 million people have sleep apnea,
hundreds of thousands have experienced narcolepsy, and approximately 12 million
suffer from restless legs syndrome or periodic limb movements during sleep.
However, most people with sleep disorders remain undiagnosed and untreated.
PMID- 9644368
TI - Principles of disinfection.
AB - For more than 150 years, we have known that medical and surgical devices may
serve as vehicles for the transmission of infectious agents to a susceptible
host. During that time, our knowledge and experience involving microbial
inactivation through disinfection have become quite sophisticated. As a result,
infectious complications associated with patient care are now the exception
rather than the rule.
PMID- 9644369
TI - Risk factors for drug-related problems in elderly ambulatory patients.
AB - Medication use among elderly patients in ambulatory care, home health care, and
long-term care settings has become increasingly complicated during the past
decade. Home intravenous therapy, multiple drug regimens to treat multiple
chronic diseases, increased acuity of nonhospitalized patients, and increased
longevity have placed elderly patients at increased risk for drug-related
problems.
PMID- 9644370
TI - Home health industry feels impact of new Medicare changes.
PMID- 9644371
TI - The most appropriate health care in the right place, and the right time. The
importance of clinical decision support criteria in home health care.
PMID- 9644372
TI - Evaluating support services to seniors. A discussion of collaborative research.
AB - The difficulties involved in attempting to turn collaboration into partnership
are revealed in this article about the relationship between research funders and
researchers, specifically government funders and university researchers. Some
discussion revolves around the relationships between researchers and among the
researchers, practitioners, and consumers. This article also discusses
collaborative research relationships by using the evaluation of a support program
to seniors as an illustration. Also addressed are how the research revealed the
success of the program and the frustrations encountered when government would not
act on the findings.
PMID- 9644373
TI - Diversity and aging. Cultural understanding as a powerful force in patient
centered healing.
AB - Culture describes a group whose members share common beliefs, values, traditions,
symbols, language, and socialization styles. As an individual moves through the
stages of life, he or she experiences a variety of cultures through membership in
families, jobs, communities, and churches. Each culture contributes to the unique
composition of a given individual. It comes as no surprise that elders older than
60 present the most diversity of any age group. This article discusses that
diversity and assumptions that challenge the health care provider working in the
community.
PMID- 9644374
TI - Exercise, immunity, acute respiratory infections, and homebound older adults.
AB - Appropriate exercise may enhance immune function and lessen acute upper and lower
respiratory tract infection (ULRI) symptoms in older adults. Home health care
professionals need to know about this potential exercise effect because increased
disease resistance and well-being can have a direct impact on activities of daily
living (ADL) and independence. This article discusses recent exercise immunology
research results, briefly explains the pathways by which exercise might affect
immunity and ULRI, and provides guidance for home health care personnel regarding
the delivery of an exercise program for their clients.
PMID- 9644375
TI - American Subacute Care Association. Comparing OASIS, FIM, and MDS in assessing
disability.
PMID- 9644376
TI - How much is too much?
PMID- 9644377
TI - Home healthcare nursing in the managed care environment. Part II. The impact on
clients and professional nurses.
AB - Part I, published in last month's issue of Home Healthcare Nurse, provided
information about managed care and health maintenance organizations (HMOs). This
article, Part II, presents an overview of the history of home healthcare nursing,
the results of a purposeful sample, and interviews of home care nurses.
Interviews were conducted to determine how nurses perceived the impact of managed
care on their clients and nursing practice. Conclusions are presented in terms of
emergent categories gleaned from the interviews. Recommendations for the
continued growth and advancement of professional nursing in the context of
managed care are given.
PMID- 9644378
TI - Volunteers as members of the home healthcare and hospice teams.
AB - A volunteer program has multiple advantages to the patients, their families,
their nurses, the hospice, and the volunteers themselves (Harris, 1990). Home
care volunteerism make good sense. If properly administered, it is cost-efficient
and delivers a quality of care that can be acquired in no other way (Sodano,
1997;764). Given the many changes that continue to take place in home healthcare
and hospice regulations and financing, volunteers are a vital component of both
programs so that patients and families continue to receive high-quality care.
Volunteers are important members of the home healthcare and hospice teams.
PMID- 9644379
TI - Postpartum home visits: extending the continuum of care from hospital to home.
AB - Crucial maternal, newborn, and family healthcare needs arise during the early
postpartum period, providing the opportunity for home care nurses to extend the
continuum of care from hospital to home. This study identifies common early
postpartum problems discovered on home health visits and describes the related
interventions of home health nurses. Correlational analysis revealed that young
mothers, first-time mothers, breastfeeding mothers, and single mothers are
priority candidates for follow-up home care.
PMID- 9644380
TI - Using community resources effectively to plan care.
PMID- 9644381
TI - Developing collaborative multisite research in home care.
AB - This article present the collaborative process for conducting research among a
state home care foundation, its associated membership, and a university. Research
collaboration allowed the merging of talents and resources from persons, home
care agencies, and a university. The history and development of the project,
sampling procedure, and data collection and analysis are discussed. The project
increased the appreciation for research, allowed an opportunity for scholarly
exchange, and accented the positive use of resources in all settings.
PMID- 9644382
TI - Exaggerating the capability to provide care in the home: more than just
"puffing"?
PMID- 9644383
TI - Urinary tract infections in the homebound elderly.
AB - The incidence of bacteriuria is widespread in the elderly. Because home care
nurses serve elderly clients with multiple problems, bacteriuria is often
encountered in the home care setting. The elderly may present with typical signs
and symptoms of infection. However, the indications are often vague and
nonspecific. Bacteria in the urine often presents with no symptoms and is best
left untreated. The responsibilities of the nurse include evaluating signs and
symptoms presented by their clients and overseeing therapeutic plans, specimen
collection, infection control practices, catheter care, education, and
prevention. It is important that prevention always receive top priority.
PMID- 9644384
TI - Frequently asked questions about warfarin sodium.
PMID- 9644385
TI - Preparing for the home health nurse certification examination.
AB - Becoming certified in an area of nursing practice is one way of demonstrating
expertise and competency in that area. Proper preparation is the key to
successfully become certified. Study hints and test-taking strategies are
discussed in detail. Specific information is provided on preparation to take the
American Nurses Credentialing Center (ANCC) Generalist Home Health Nurse
certification examination.
PMID- 9644386
TI - Home care nursing: satisfaction.
PMID- 9644387
TI - Ars Moriendi: illuminations on 'the good death' from the arts and humanities.
PMID- 9644388
TI - Hospice: current practice, future possibilities.
PMID- 9644389
TI - Managed, capitated care: opportunities for good and evil.
PMID- 9644390
TI - Pain, symptoms, and suffering: possibilities and barriers.
PMID- 9644391
TI - Visions and strategies: what participants and others might do.
PMID- 9644392
TI - Demography and epidemiology of dying in the U.S. with emphasis on deaths of older
persons.
AB - As chronic disease continues to be the major cause of death and as the elderly
population grows, it is important to evaluate the adequacy and completeness of
health care strategies for the elderly. Two studies, the National Mortality
Followback Survey and the National Institute on Aging Survey of the Last Days of
Life, were designed to examine the circumstances of death for representative
samples of decedents. Four areas of focus are location of death, transitions
among health care settings, circumstances at the time of death, and changes in
physical and cognitive function in the last year of life. Although the data are
helpful for family planning, they are limited by a lack of data on costs.
PMID- 9644393
TI - A history of the Medicare hospice benefit.
AB - Since the inception of the Medicare hospice benefit, hospice has marked a new
approach to managed care. Its focus on cost-effectiveness has made it one of
Medicare's most successful managed care options. Various restrictions were placed
on the hospice program; but, in return for these limitations, advocates of the
program received an opportunity to create a program entirely different from other
Medicare providers. The challenges of operating a hospice include electing
hospice care, candid communication, and the relationship with other providers.
These challenges will continue to burden hospices until discussions of death can
be direct, clear, and knowledgeable.
PMID- 9644394
TI - Predicting patient survival before and after hospice enrollment.
AB - Despite the apparent advantages of hospice care, several barriers exist in terms
of patient referral. Physicians' prognoses play a large role in determining when
hospice care should begin. Predicting patient survival is a subjective decision
dependent on several factors that vary before and after hospice enrollment.
Currently, the stay of patients in hospice is very short; this can be attributed
to late referral by physicians. Additional research on physician behavior and
prognostication could help optimize the use of hospice as a valuable health care
resource, thereby improving end of life care for terminally ill patients.
PMID- 9644395
TI - Pain and the barriers to its relief at the end of life: a lesson for improving
end of life health care.
AB - Pain among cancer patients is a common distressing symptom that frequently
affects physical functioning, social interaction, psychological status, and
quality of life. Despite the extensive body of knowledge available regarding
cancer pain assessment and management, it often remains untreated, thereby
diminishing the quality of patient care at the end of life. Recommendations on
how to remove these barriers, as well as to improve care of the dying in general,
need to be implemented by the U.S. government.
PMID- 9644396
TI - Why not the best for the chronically ill?
AB - Premium adjustors to neutralize risk selection among health plans are the weakest
component in the technology for assuring competitive markets. It will be many
years before we have adjustors adequate to free health plans to invest in and
market improved managed care to predictably high-cost chronically ill persons.
For want of a fair premium, health plans are driven by risk selection to
underinvest in and otherwise "demarket" care to these very employees and
beneficiaries whose costs and care most need to be managed. To achieve best value
for the chronically ill, large employer coalitions, Medicare, and Medicaid should
consider radical new approaches, such as establishing separate prices for care to
people with specific chronic conditions and purchasing such care both from health
plans and directly from provider systems.
PMID- 9644397
TI - The importance of measuring quality of care at the end of life.
AB - Although designed to respond to acute illness, the current health care system
must increasingly provide care for people living longer with chronic diseases.
Evaluation of the quality of this care must utilize appropriate measurements,
study populations, and outcomes. Current quality measures and major studies of
quality of care are highlighted. A framework for measuring quality of care is
outlined.
PMID- 9644398
TI - An update on efforts by the hospice community and the National Hospice
Organization to improve access to quality hospice care.
AB - More than a year has passed since the Center to Improve Care of the Dying and the
Corcoran Gallery of Art sponsored the symposium entitled: A Good Dying: Shaping
Health Care for the Last Months of Life. Using the National Hospice Foundation
sponsored exhibition, Hospice: A Photographic Inquiry, as a backdrop, the
symposium included presentations on the current state of hospice care as well as
the obstacles that limit access to hospice care. This article represents an
update on many of the activities of the National Hospice Organization and the
greater hospice community as we continue to improve access to quality hospice
care.
PMID- 9644399
TI - Overview on ABIM End-of-Life Patient Care Project: caring for the dying:
identification and promotion of physician competency.
AB - The American Board of Internal Medicine's project to improve end-of-life care was
initiated in response to lack of attention given to death and dying in the United
States. The project focuses mainly on physician competency in residency and
fellowship training. With this data, recommendations can be made to improve
physician training in end-of-life care treatment.
PMID- 9644400
TI - Quality end of life care: the case for a MediCaring demonstration.
AB - People in the last phase of life often need a very different care system than the
one currently available. MediCaring extends the hospice model to a larger
population with a wider array of services over a longer period of time with an
emphasis on symptom management, maintenance of function, comfort and family
counseling. This model requires simultaneous efforts to secure longer life and to
make the patient and family ready for dying. Services range from psychological
and spiritual counseling for the patient and family, to emergency care access, to
inpatient respite care. MediCaring would accomplish these goals without
increasing costs, primarily by diminishing the use of acute care interventions
that may no longer serve the patient.
PMID- 9644401
TI - New endeavors and innovative programs in end of life care.
AB - This paper presents summaries of initiatives and demonstration programs developed
by professional and patient care organizations to improve care at the end of
life.
PMID- 9644402
TI - Case management in a rural context.
PMID- 9644403
TI - Managed care, health care reform, and the role of providers of aging services.
Devolution threatens the safety-net role played by the federal government.
AB - Managed care which emphasizes the rationalization of the way health care is
financed, the devolution movement which shifts greater program responsibility to
the state and local levels, and the restructuring of Medicaid along the lines of
a block grant program, are issues presenting providers of aging services with a
daunting set of challenges and opportunities. Providers of aging services will
need to build on existing strengths, while developing new strategies, to succeed
under an environment of managed care and state and local funding control.
PMID- 9644404
TI - Barriers to providing case management to older rural persons.
AB - This article analyzes data from a national sample of 356 agencies on barriers to
providing case management to rural older persons. Although considerable variation
is found regarding the degree of difficulty attributed to various barriers,
several areas are reported by respondents as problematic, such as a lack of
resources to pay for case management and services, a lack of services, and a lack
of transportation. On the other hand, a lack of rural case management standards,
qualified persons to conduct case management, and opportunities for staff
training, as well as staff turnover and professional isolation, are generally not
seen as particularly troublesome. More support from families and personal
knowledge of clients and service providers are most likely to be seen as
advantages in providing case management to rural elders. These findings both
support and contradict the current gerontological literature on the types of
barriers that impede the development and provision of services to rural older
persons. Additional research is needed on the barriers to providing case
management to rural older persons before policies directing scarce resources are
put into place.
PMID- 9644405
TI - Interactive televideo and the Internet in rural case management.
AB - The purpose of this article is to stir the imagination and incite the creative
energies of case managers in finding ways to capitalize on communication and
information technologies to improve access to care as well as the quality of care
in rural communities. Today, the general dearth of services and logistics of
providing services in rural areas challenges even the most seasoned case
managers. Given the current economic and political climate, it is unlikely that
these challenges will lessen, particularly if we continue to pursue our more
traditional approaches to case management and service delivery.
Telecommunications technologies are opening exciting opportunities for changing
this trajectory and expanding the role and reach of case managers, while
improving access to many services. This article highlights the new and the
potential applications of interactive televideo in health and human services, as
well as the vast opportunities offered by the Internet. There are, however, also
pitfalls we must overcome to realize the full potential of these technologies.
Case managers, in their roles as advocates, coordinators, and facilitators, are
ideally positioned to be on the cutting edge of these technological applications
and play a catalytic role in moving rural communities into the "information age."
PMID- 9644406
TI - Rural mental health and aging: implication for case management.
AB - Older adults are underrepresented as recipients of mental health services,
despite evidence that preventive interventions are effective and complement
physical health interventions. Barriers to using these services include the
stigma associated with mental health problems, lack of trained professionals and
general barriers of availability and accessibility in rural service delivery.
Case managers can play an important role in breaking down some of these barriers
and assisting older adults to access t-ese services. Several outreach and
educational models have been developed that are replicable and available to case
managers.
PMID- 9644407
TI - Formal home care services: examining the long-term care needs of rural older
women.
AB - Little data or current research exists regarding the specific long-term care
needs of rural older women. This article examines the variables that appear to
influence the availability of formal home care services. Utilization is discussed
within the context of the specific social, cultural, and demographic factors that
are applicable to this group of individuals. A description of the unique health
care considerations of older women is also presented, along with recommendations
for future research efforts and programming initiatives.
PMID- 9644408
TI - Decision making by high functional status elders regarding nursing home
placement.
AB - An analysis of the Minimum Data Set Plus (MDS+) from one midwestern state
revealed a group of "high functional elders" entering nursing homes, who
potentially could be served in the community at a lower cost. The purpose of this
qualitative study was to identify and better understand the reasons why these
apparently high functioning elder adults entered nursing homes. Data from the
1995 MDS+ were used to identify "high functional" elders recently admitted to the
nursing home from two urban and seven rural counties. Data were collected through
in-depth, face-to-face, semi-structured interviews and analyzed using qualitative
content analysis. Of the 33 persons judged to be high functional, only 36%
remained in the nursing home 3 to 6 months later. Most elders were using a wide
array of community-based services and extensive informal support networks prior
to entering the nursing home. Most described specific events that forced them
into the nursing home environment. Health needs, specifically the need for 24
hour care or supervision, emerged as the dominant factor for remaining in the
nursing home. Of the 12 elders interviewed, all demonstrated some evidence of
cognitive impairment. This study suggests that there are persons in nursing
facilities today for whom community-based services, such as affordable assisted
living, would be reasonable and appropriate. Case managers may be the most
qualified not only to assess for and coordinate services, but also to advocate
for affordable services that preserve elders' functional status.
PMID- 9644409
TI - I want to live here for rest of my life. The challenge of case management for
rural seniors.
AB - The research on long-term care for seniors clearly demonstrates that efforts to
integrate urban case management services with elderly people living in rural
settings have not been successful. Presenting findings of the Rural Seniors
Assisted Living Study conducted in northwestern Ontario, Canada, this article
demonstrates the complexity of providing health and social services for seniors
living in small rural communities, services that are often vastly different from
those provided in urban communities. The article proposes a specialized Rural
Case Management approach with rural elderly clients and identifies four
intervention roles: providing direct service, consulting extensively with
specialists of other disciplines, constructing and supporting natural helping
networks, and resource management. The approach also requires that the rural case
manager assume a leadership role at the community level in the development of
services for seniors. Having a locally based case manager rather that a case
manager who travels out to rural areas from an urban center is essential to the
success of this rural case management approach. Finally, the article contends
that rural case management differs from urban case management by requiring
specialized knowledge, skills and educational programs.
PMID- 9644410
TI - Outcomes associated with advanced nursing practice prescriptive authority.
AB - Thirty-three advanced practice nurses (APNs) in 25 different primary care sites
in one state participated in a study of the safety and effectiveness of APN
prescriptive authority. Data were analyzed on 1,708 patients seen during a 2
month period. Outcomes of care were studied using three different measures as
well as patient satisfaction. Evaluation of patient outcome by APN and physician
indicated that in 76% of the cases, the patient's condition stabilized or
improved. Patients evaluated their own outcomes positively. Participating
physicians were unanimous in their evaluation of APN prescriptive authority as
beneficial to their patients.
PMID- 9644412
TI - Cardiac information on the Internet.
PMID- 9644413
TI - Vulvodynia: diagnosis and management.
PMID- 9644411
TI - A preliminary study of the use of peer support in smoking cessation programs for
pregnant adolescents.
AB - This article describes preliminary findings of an experimental, randomized, three
group, controlled design examining the effectiveness of a smoking cessation
intervention for pregnant teens. The three groups are: Teen FreshStart with a
buddy program (TFSB), a Teen FreshStart program (TFS) without peer support, and
the Usual Care (UC) control group. Forty-six subjects completed the post
intervention assessment of smoking status. The TFSB group consistently achieved
greater smoking cessation across all measures when compared to the subjects in
the other two groups. These results indicate that the use of peer support may be
an effective adjunct in smoking cessation programs for pregnant adolescents.
PMID- 9644414
TI - Pulmonary contusions: management and implications for trauma nurses.
AB - TOPIC: Pathophysiology of pulmonary contusions, current methods for assessing
blunt chest trauma patients, pulmonary parameters and diagnostic methodology, and
innovative ventilatory treatment. PURPOSE: To heighten awareness of pulmonary
contusion, the treatment and potential sequelae. SOURCES: Published information
and clinical experience. CONCLUSION: A pulmonary contusion is a common
potentially lethal chest injury seen in this country. Trauma clinicians should
have heightened awareness about this injury because the injury is often
overlooked and the clinicians frequently do not comprehend the mechanisms causing
pulmonary contusions.
PMID- 9644415
TI - Case study: trauma care in a nontrauma center.
PMID- 9644416
TI - Trauma service quality assurance and improvement summary form.
PMID- 9644417
TI - Supreme Court issues decisions in assisted suicide cases.
PMID- 9644418
TI - From cacophony to symphony: healthcare needs a conductor.
PMID- 9644419
TI - Clinical management protocols: the bedside answer to clinical practice
guidelines.
AB - TOPIC: Clinical Management Protocols for trauma patients. PURPOSE: The goals and
process for developing and implementing Clinical Management Protocols are
presented. Protocol development and the differences between clinical practice
guidelines, critical pathways, and clinical management protocols are discussed.
SOURCES: Published literature, experience, and clinical expertise. CONCLUSIONS:
Utilizing annotated algorithms, the protocols are designed for and driven by
patient care based on patient need and require the collaboration of experts and
trauma team members.
PMID- 9644420
TI - Trauma prevention: an evaluation tool for youth and alcohol trauma-prevention
programs.
AB - PURPOSE: To evaluate the Student Alcohol Questionnaire (SAQ) for use
drinking/driving prevention programs in college-age students. METHODS: A pilot
study of 39 students was conducted, which included a pre-test covering
demographics and using the SAQ. A post-test was given as a program evaluation.
The SAQ was repeated one month later. FINDINGS: At program completion, 40% of
students stated that they would change behavior. The SAQ findings revealed no
statistically significant changes in the pre- and post-tests. CONCLUSIONS: The
SAQ may be an effective tool for measuring prevention programs.
PMID- 9644421
TI - The top ten things to know and recognize when caring for adult victims of
domestic violence.
PMID- 9644422
TI - The Trauma Center Survival Questionnaire.
PMID- 9644423
TI - Making education relevant to clinical practice.
PMID- 9644424
TI - Wound management in staged abdominal repair.
PMID- 9644425
TI - Measuring interface pressures in mattresses.
AB - This evaluation compared the pressure support qualities of three mattresses by
measuring the interface pressures using 20 subjects. The results indicate that
the Pegasus Airwave mattress had significantly higher readings than Quattro
DC2000 (p = 0.021, 95% confidence level) and the Nimbus II (p = 0.009, 99%
confidence level) but that there is no significant difference between interface
pressures for the Quattro DC2000 and the Nimbus II.
PMID- 9644426
TI - Evaluating pressure-relieving mattresses.
AB - In this study, three mattresses were evaluated to assess their effectiveness in
relation to the pain and discomfort experienced by 40 patients with neurological
disorders who had Waterlow scores > or = 15 and required pressure support. The
results indicate that one mattress (the Quattro DC2000) performed significantly
better than the other two (Nimbus II and Pegasus Airwave).
PMID- 9644427
TI - An in vitro investigation of multi-layer bandages.
AB - This study compares the elastic properties of a number of different bandages both
in the non-sterile condition and after sterilisation by autoclaving at 134-138
degrees C. Results suggest that, although some products can withstand
sterilisation, the performance of some elasticated and coated bandages is
adversely affected by excessive heat.
PMID- 9644428
TI - The importance of secondary dressings in wound care.
PMID- 9644429
TI - The fatal wounding of Emperor John II Comnenus.
PMID- 9644430
TI - 1. Management practice at leg ulcer clinics. Patient examination and wound
assessment.
PMID- 9644431
TI - Management practice at leg ulcer clinics. 2. Challenges in diagnosis.
PMID- 9644432
TI - Management practice at leg ulcer clinics. 3. Factors affecting healing.
PMID- 9644433
TI - Lower limb amputation: planning surgery.
PMID- 9644434
TI - Wound assessment methods.
PMID- 9644435
TI - Epidemiological issues in monitoring pressure damage.
PMID- 9644436
TI - Women's health care: roots to recommendations.
PMID- 9644437
TI - Differential diagnosis of lower abdominal pain in women of childbearing age.
PMID- 9644438
TI - Prescribing medication in pregnancy.
AB - When prescribing medication in pregnancy, the clinician must follow some
principles of prescribing. These include timing of exposure, dosage, duration of
use, and fetal susceptibility. The health care provider must weigh the risk of
exposure to the fetus with the benefit of treatment. This article summarizes the
effect of selected medications used to treat common primary care disorders. These
disorders include gastrointestinal complaints, asthma and allergies, infections,
diabetes, epilepsy, headache, thyroid disorders, depression, and anxiety. The use
and risks associated with common medications are discussed. Although no drug can
be proven completely safe, prescribing medication with a long safety record,
avoiding exposure in the first trimester, avoiding multidrug regimens, and
prescribing the lowest dose for the shortest duration will minimize the fetal
risk.
PMID- 9644439
TI - Ovarian cancer screening: a primary care guide.
AB - Ovarian cancer is a deadly disease, rarely diagnosed in early stages when the
possibility for cure exists. A reliable screening technique would reduce the
number of late-stage diagnoses and increase the long-term survival of ovarian
cancer patients. Unfortunately, the absence of an identified premalignant phase
of the disease makes it virtually impossible to develop an effective routine
screening technique. This article reviews the risk factors related to the
increased incidence of ovarian cancer. Advanced age and factors related to
incessant ovulation, such as early menarche, late menopause, nulliparity, or few
pregnancies, have been shown to increase a woman's chance of developing ovarian
cancer. Also, a family history of endometrial, colon, breast, or ovarian cancers
may increase the likelihood of developing the disease. The role of the primary
care provider in the identification of high-risk individuals is reviewed, and
currently available early detection test such as pelvic examination, CA-125,
abdominal or pelvic ultrasound, and color-flow Doppler technique are summarized.
PMID- 9644440
TI - Telephone triage in women's health care.
AB - This article describes the importance of sound telephone triage strategies in
women's health care. A brief description of the history of telephone triage is
provided as well as basic considerations in establishing a telephone triage
system. A sample telephone report sheet is also provided.
PMID- 9644441
TI - Menopause: providing comprehensive care for women in transition.
AB - Knowledge and research on the physiological changes associated with menopause is
steadily expanding. A partnership between women and health care providers can
contribute to the quality of women's life expectancy which is estimated to be
79.1 years (United States Bureau of Census, 1993). Menopause is a normal
phenomena of aging and women experiencing menopause must have access to
comprehensive care, including a complete history, thorough physical exam, risk
factor and age-appropriate screening, and patient education. Studies confirm
women's lack of knowledge concerning menopause and the need for education on
bodily changes and approaches to self-care during transition. Decline in the
ovarian production of estrogen and the feedback effect of gondatropins leads to
an increased follicle-stimulating hormone (FSH) of 40 mlU/mL. Vasomotor flushing,
night sweats, vaginal dryness, shortening of the menstrual cycle with heavy flow
progressing to longer cycles and scant flow and eventual cessation of menses for
a period of 12 consecutive months confirms menopause. A program of screening and
education for self-care can enhance women's quality of life.
PMID- 9644442
TI - Breast cancer and gene testing: risk, rationale, and responsibilities of primary
care providers.
AB - Family history is one of the known risk factors for breast cancer. Breast cancer
susceptibility genes, BRCA-1 and BRCA-2, have been identified as accountable for
less than 10% of all cases of breast cancer. Certain populations however,
including native Icelanders and Ashkenazi Jews have a higher incidence of BRCA
mutations than the general population. Genetic testing for these mutations is now
available. Many ethical issues remain regarding who should be tested and what
interventions should be carried out with positive test results. This article
describes the patient assessment and counseling process for breast cancer testing
to improve the knowledge base and confidence of the primary care provider.
PMID- 9644443
TI - Shortened lengths of stay: ensuring continuity of care for mothers and babies.
AB - Hospital discharge on the day after an uncomplicated vaginal delivery may be
appropriate if clinical criteria are used for the selection of patients and post
discharge follow-up plans are in place. To ensure safety for these patients,
Advocate Health Care developed a mother/baby philosophy statement, guidelines for
maternal and infant discharge in less than 48 hours, and an algorithm to assure
that appropriate follow-up care takes place after discharge. To evaluate the
Mother/Baby Home Transition Program, home health follow up, readmission rates,
and sentinel events were tracked. Most home health visits occurred within 48
hours. Infant readmission rates ranged from 1.1-2.6%, whereas maternal
readmission rates ranged from 0-0.52%. Three sentinel events in 1996 and three in
1997 required readmissions to an ICU. Data continue to be monitored and shared
monthly with clinical leaders.
PMID- 9644444
TI - "Natural" hormone replacement therapy and dietary supplements used in the
treatment of menopausal symptoms.
PMID- 9644445
TI - Herpes genitalis.
PMID- 9644447
TI - Preventing and recognizing STDs.
PMID- 9644446
TI - Pelvic inflammatory disease.
PMID- 9644448
TI - Understanding the abnormal Pap smear.
PMID- 9644449
TI - Preparing for colposcopy.
PMID- 9644450
TI - Unraveling the mystery of chronic amenorrhea.
PMID- 9644451
TI - Hepatitis in the ESRD setting: defining the risks.
AB - Although hepatitis can be a significant problem for dialysis patients and staff,
the risk of contracting hepatitis can be reduced. Next month, part two will
address preventive strategies that may be utilized to reduce the risk of
transmission of hepatitis between patients and staff.
PMID- 9644452
TI - After 10 years, the OPTN regulations arrive--what's next?
PMID- 9644453
TI - Improving communication between patients and staff.
PMID- 9644454
TI - Mediation: one method of resolving patient/staff differences.
PMID- 9644455
TI - Monitoring quality of care.
PMID- 9644456
TI - Patients' rights and responsibilities: a physician's view.
PMID- 9644457
TI - Bringing advanced technologies of the Internet into the dialysis unit.
PMID- 9644458
TI - Renal transplantation in Canada.
PMID- 9644459
TI - DOQI guidelines and the vascular access puzzle: finding the pieces that fit.
PMID- 9644460
TI - Specialist practice: the transitional arrangements.
PMID- 9644461
TI - The minute paper: a quick guide to assessing student learning.
PMID- 9644462
TI - Learning from the experiences of mental health nurses.
PMID- 9644463
TI - The psychology of health promotion.
PMID- 9644464
TI - Making sense of data.
PMID- 9644465
TI - Becoming a manager and making a difference to patient care.
PMID- 9644466
TI - Keep bad news about NHS out of the press.
PMID- 9644467
TI - Working with nursing agencies.
PMID- 9644468
TI - Strategic management for elderly care.
PMID- 9644469
TI - An initiative in mental health nursing.
PMID- 9644470
TI - Staff attitudes to clinical placements.
PMID- 9644471
TI - Education for the future.
PMID- 9644472
TI - Wilma McPherson -- the interview. Interview by Tom Keighley.
PMID- 9644473
TI - Providing effective clinical supervision.
PMID- 9644474
TI - Promoting change through peer review.
PMID- 9644475
TI - The lobbying power of nurses.
PMID- 9644476
TI - Relationships among HIV risk beliefs, attitudes, and behaviors in sexually
active, seronegative gay men.
AB - Safer-sex guidelines established during the early days of the HIV/AIDS epidemic
have undergone very little revision despite some controversy. Although these
guidelines have been widely disseminated in the gay community, many gay men
continue to engage in behaviors that are believed to put them at high risk for
transmission of HIV. This suggests either that they have not accepted safer-sex
guidelines as accurate or that other factors override personal implementation of
the guidelines. The study examined seronegative gay men's beliefs about the
accuracy of safer sex guidelines and the men's participation in behaviors risky
for transmitting HIV. The greatest disagreement between the men's beliefs and
behaviors centered on the risk of oral intercourse; this suggests a need for
clarification of the safer sex message about this behavior. The findings of this
study support the need to reformulate safer-sex guidelines. When unprotected oral
and anal sex are classified at the same level of risk, those who engage in
unprotected oral sex may proceed to unprotected anal sex with less reservation.
PMID- 9644477
TI - Does mandating continuing education mandate competence?
PMID- 9644478
TI - Nursing education accepts new challenges.
AB - This paper describes an innovative experience in which nursing students made home
visits to postoperative patients. It was planned in cooperation with surgeons and
nurses in the outpatient surgery department. Objectives for this experience were
defined and students evaluated the effectiveness of their preoperative teaching
and monitored the patients for potential complications.
PMID- 9644479
TI - Advocacy and allocation.
PMID- 9644480
TI - Role-modeling experience improves nursing students' attitudes toward people
living with AIDS.
AB - Two groups of student nurses were given on AIDS Knowledge/Attitudes survey before
different clinical experiences. Group One worked with nurses experienced in the
care of persons living with AIDS (PLWA) on a high-acuity unit with many AIDS
patients. The other group were precepted on a acute-care unit with no AIDS
patients. Outcomes measures revealed significantly better student attitude scores
for Group One on scales measuring (1) avoidance intentions to working with PLWA
and (2) attitude toward homosexuals.
PMID- 9644481
TI - Multistate licensure: to support or not to support.
PMID- 9644482
TI - Self-efficacy: an essential component of advanced-practice nursing.
AB - The concept of self-efficacy has been used widely as a model for examining health
promoting education in such areas as cardiac rehabilitation, smoking cessation,
dietary modifications, pulmonary rehabilitation, and compliance with prescribed
regimens. Consequently, self-efficacy has emerged as an essential concept in
developing and implementing health promotion programs in advanced practice. Self
efficacy refers to an individual's perceived ability to perform a specific
behavior. It is the mediator between knowledge and action, and it influences the
selection of behavior, the environment in which the behavior occurs, and the
amount of effort and perseverance expended on performing the behavior. This paper
analyzes the concept of self-efficacy and suggests applications of self-efficacy
in advanced-practice nursing.
PMID- 9644484
TI - Taking care with language.
PMID- 9644483
TI - The effectiveness of guided design on ethical decision making and moral reasoning
among community nursing students.
AB - This study evaluated the effectiveness of guided design as an instructional
method in ethical decision making and moral reasoning among 145 community health
nursing students. Changes in the process of ethical decision making and moral
reasoning were measured using Ketefian's judgment About Nursing Decisions (JAND)
one week after the intervention. Results indicated a significant difference in
ethical decision-making scores after instruction, but no difference in moral
reasoning. The one specific component--Taking professional initiatives--increased
on both subscales.
PMID- 9644485
TI - Canadian contrasts.
PMID- 9644486
TI - Reflections on the process of play interaction.
PMID- 9644487
TI - Practical pathways: a multidisciplinary approach to asthma.
PMID- 9644488
TI - Prolonged contact with topical anaesthetic cream: a case report.
PMID- 9644489
TI - Psychological stress in critical care.
PMID- 9644490
TI - 'How d'you know it's me'?
PMID- 9644491
TI - Childhood diabetes: dietary aspects.
PMID- 9644492
TI - Old habits. Will you pay for your past as a smokers?
PMID- 9644493
TI - Impotence. Putting the pill (for men) in perspective.
PMID- 9644494
TI - My doctor told me I tend to get dehydrated. Can I substitute other liquids for
water?
PMID- 9644495
TI - Temporal arteritis. A serious, mysterious headache.
PMID- 9644497
TI - Folic acid and diet.
PMID- 9644496
TI - Herbal insurance. Does an allium a day keep the doctor away?
PMID- 9644498
TI - Exercise prevents gallstones.
PMID- 9644499
TI - Sildenafil (Viagra): the new pill for impotence.
PMID- 9644500
TI - Walking to health.
PMID- 9644501
TI - The crucial, controversial carotid artery. Part II: Treatment.
PMID- 9644502
TI - Prostate cancer: a new clue.
PMID- 9644503
TI - My question, our 12-year-old son. Almost every time he eats ice cream he gets a
terrible headache. I don't think he is allergic to milk, since he drinks it by
the quart. What's wrong?
PMID- 9644504
TI - The trauma of serious illness.
PMID- 9644505
TI - Do you need cholesterol-lowering drugs?
PMID- 9644506
TI - A new alternative to estrogen: raloxifene.
PMID- 9644507
TI - Senior drivers.
PMID- 9644508
TI - Prostate cancer test becomes more accurate.
PMID- 9644509
TI - Allergic shock reaction.
PMID- 9644510
TI - Calming ulcerative colitis.
PMID- 9644511
TI - Exercise improves swallowing.
PMID- 9644512
TI - Pain killers and diverticulitis.
PMID- 9644513
TI - Are multiple health problems undertreated?
PMID- 9644514
TI - Lyme disease vaccine.
PMID- 9644515
TI - [Scientific heritage of Z.V. Ermol'eva and present].
PMID- 9644516
TI - [On the history of penicillin preparation by Z.V. Ermol'eva].
PMID- 9644517
TI - [Z.V.Ermol'eva: cholera control and prevention--her life commitment].
PMID- 9644518
TI - [Contribution of Z.V.Ermol'eva to the research in the field of highly dangerous
infections].
PMID- 9644519
TI - [Studies of Z.V.Ermol'eva and her school in the field of isolation and
characterization of lysozyme].
PMID- 9644520
TI - [Biologically active compounds and scientific heritage of Z.V.Ermol'eva].
PMID- 9644521
TI - [Interferons in cascade of cytokines: historic and modern aspects].
PMID- 9644522
TI - [Studies of Z.V.Ermol'eva on antitumor effect of biologically active substances
of animal origin].
PMID- 9644523
TI - [Combined antibiotic therapy--one of the ways of increasing antibiotic efficacy].
PMID- 9644524
TI - [Z.V.Ermol'eva--scientist and teacher].
PMID- 9644525
TI - [Amoxycillin/clavulanic acid--beginning of new era in antibiotic therapy of
bacterial infections].
PMID- 9644526
TI - [Antibiotics: new mechanisms of resistance transfer].
PMID- 9644527
TI - [Stepwise therapy of community-acquired pneumonia. Results of cefuroxime and
cefuroxime axetil study].
AB - The efficacy of a 7-day switch therapy with parenteral cefuroxime in a dose of
750 mg for 3-5 days followed by the use of oral cefuroxime axetil in a dose of
500 mg every 12 hours was compared with that of a 7-day therapy with parenteral
cefuroxime in a dose of 750 mg every 8 hours in hospitalized patients with
community-acquired pneumonia. The clinical and bacteriological efficacies and
pharmacokinetic properties of both the dosage forms were estimated. It was shown
that the clinical and bacteriological effects did not significantly differ in the
patients under the parenteral regimen with cefuroxime and under the parenteral-to
oral regimen with cefuroxime and cefuroxime axetil: the cure in 75 and 83 per
cent of the patients and the bacteriological response in 100 and 86 per cent of
the cases respectively. The results indicated that the cost of the switch therapy
was much lower while the efficacy did not decrease.
PMID- 9644528
TI - [Ceftriaxone in the treatment of staphylococcal endocarditis].
AB - Efficacy and safety of ceftriaxone (Oframax, Ranbaxy, India) in the treatment of
25 patients with Staphylococcus endocarditis (SE) were studied. The drug was
administered intravenously in a dose of 2-4 g a day for 4 weeks and
simultaneously gentamicin was used intramuscularly in a dose of 2-3 mg/kg body
weight a day every 8 hours for 2 weeks. The treatment was followed by observation
of the patients for up to 2 years under the hospital or dyspensary conditions.
The disease was due to S. epidermidis (17 patients) or S.aureus (8 patients). The
efficacy was controlled in the dynamics. The criteria of the therapy efficacy
were disappearance of the disease clinical signs, normalization of the blood
count and urinalysis and the pathogen eradication by the results of the control
bacteriological blood analysis. The cure without any surgical correction was
observed in 68 per cent of the patients and that with the valve replacement was
stated in 24 per cent of the patients. The lethal outcome due to bacteriotoxic
shock was recorded in 8 per cent of the patients. The SE relapsing was stated in
28 per cent of the patients 3 or more months after the ceftriaxone therapy
completion. 10 patients (40 per cent) with evident clinicolaboratory improvement
were discharged from the hospital 2 (4 patients) and 3 (6 patients) weeks after
the therapy start for the treatment with ceftriaxone as outpatients. In 2
patients nausea as the adverse reaction was observed. Therefore, the complex
clinicolaboratory investigation showed that the combined use of ceftriaxone and
gentamicin was efficient and safe in the treatment of SE. Ceftriaxone may be
considered as a basic drug for the therapy of SE. In some patients with SE the
treatment with ceftriaxone may be completed under outpatient conditions.
PMID- 9644529
TI - [Clinical and laboratory study of cefodizime (Modivid) in prophylaxis and
treatment of surgical patients].
AB - The results of the clinical and laboratory study of the efficacy of the
prophylactic and therapeutic use of cefodizime (modivid) in patients with chronic
calculous cholecystitis and burns are presented. Expediency of the preoperative
prophylactic use of the drug and its significance in the treatment of infectious
complications of the burn disease were verified. The immunological investigation
gave evidence of an increase of the phagocytosis functional activity when
cefodizime (modivid) was used prophylactically in cholecystectomy.
PMID- 9644530
TI - [Isolation and identification of Mycobacterium cultures antagonistic to
phytopathogenic microflora].
AB - A number of saprophytic bacteria were isolated from natural substrates. Their
identification showed that the majority of the isolates belonged to the genus
Mycobacterium. The previously developed test-system including treatment of soil
substrates by alkali and the use of optimal nutrient media provided preferencial
isolation of saprophytic mycobacteria. The primary studies demonstrated that the
cultures belonging to the genus Mycobacterium had antifungal properties and might
be promising for screening antagonists of phytopathogens.
PMID- 9644531
TI - [Differential use of cephalosporins in treatment of upper and lower respiratory
tract infections].
PMID- 9644532
TI - [Methicillin resistant staphylococci].
PMID- 9644533
TI - [Mechanisms of macrolide resistance in organisms producing them and in
eubacteria].
PMID- 9644534
TI - [In the commission on antibiotic policy].
PMID- 9644535
TI - Regenerated hair cells become functional during continuous administration of
kanamycin.
AB - The compound action potential (CAP) was used to assess the functional status of
regenerated hair cells in the chick cochlea during prolonged administration of
kanamycin (KM). Immediately after 10 days of KM treatment, the CAP thresholds
were elevated by 6-54 dB above those from age-matched control animals. The
frequencies with the greatest threshold shifts (> 1 kHz) corresponded to the hair
cell lesion in the basal 40% of the basilar papilla. After 20 days of KM, the CAP
thresholds at 3 and 4 kHz were significantly lower than those after 10 days of KM
treatment, but virtually the same as those after 10 days of KM plus 10 days of
recovery. Similarly, the CAP amplitudes at frequencies higher than 1.5 kHz were
significantly greater in animals that received KM for 20 days than in animals
that received KM for 10 days. The threshold as well as amplitude improvement
between 10 days and 20 days of KM treatment was associated with the morphological
maturation of the regenerated hair cells in the basal 25% of the cochlea. In
addition, the rapid functional recovery seen at high frequencies coincided with
the base-to-apex gradient of morphological recovery in the basilar papilla. These
results suggest that the process of hair cell maturation is not suppressed by the
presence of aminoglycosides in the extracellular environment.
PMID- 9644536
TI - Psychopathological profile of tinnitus sufferers: evidence concerning the
relationship between tinnitus features and impact on life.
AB - This study involving 281 French tinnitus sufferers sought to investigate possible
correlations between psychopathological profile and scores obtained from three
tinnitus questionnaires. The patients all completed a French version of the Mini
Mult--a shortened Minnesota Multiphasic Personality Inventory--and French
translations of three questionnaires designed especially for the clinical
assessment of tinnitus: Tinnitus Reaction Questionnaire (TRQ), Subjective
Tinnitus Severity Scale (STSS) and Tinnitus Handicap Questionnaire (THQ).
Significant correlations were found (p < 0.0001) between scores on various Mini
Mult scales and total or factor 1 THQ and total TRQ scores. No significant
correlation was found between the STSS and any Mini-Mult score.
PMID- 9644537
TI - A 'neural' response with 3-ms latency evoked by loud sound in profoundly deaf
patients.
AB - A large negative deflection with a latency of 3 ms was observed in the auditory
brainstem response (ABR) waveforms of some patients with peripheral profound
deafness. This deflection was termed the N3 potential. In this paper, we review
patients with the N3 potential and discuss the characteristics of abnormal ABR
waveforms. The origin of the N3 potential was also discussed, especially with
respect to vestibular evoked potentials. In most of the patients, audiograms
showed no response to the maximum output of an audiometer in the high-frequency
range and a residual response in the low-frequency range. The N3 potentials were
noted at intensities of 80 dB nHL or greater. As the stimulus intensity
increased, the amplitude of the potential increased and the latency decreased. A
high repetition rate (83.3/s) of the click stimulus influenced the latency and
amplitude of the N3 potential. The potential was replicated on retest within less
than a month, and had a consistent latency and amplitude over the scalp. The
results indicate that the N3 potential is not an electrical artifact but a
physiological neural response evoked by a loud sound. The N3 potential is most
likely not an auditory evoked response from cochlear or a response from a
semicircular canal, because it has a 3-ms latency, a sharp waveform, and is
unassociated with vertigo. The results suggest that the N3 potential may be a
saccular acoustic response.
PMID- 9644538
TI - Three-dimensional reconstruction of the auditory cortical areas from magnetic
resonance images.
AB - The future of neuromagnetic research will be highly dependent on the development
of analysis procedures utilizing morphological information derived from magnetic
resonance (MR) images. However, constraining the biomagnetic inverse problem by
using such information may lead to serious misinterpretations if the
reconstruction algorithm for the cortical surface overlooks boundaries between
grey matter and cerebrospinal fluid (CSF) or artificially generates them. The
purpose of this study was to check as to what extent an advanced automatic three
dimensional reconstruction procedure is able to segment the cortical structures
located hidden in the Sylvian fissure (especially Heschl's gyrus and planum
temporale). The procedure consisted of four processes: a coarse segmentation, a
refined segmentation of the white matter, a skeletonization of the sulci and a
segmentation of the cortical surface by concurrent region growing for brain and
CSF. The reconstruction result for single slices basically agrees with the
impression obtained upon visual inspection of the original MR data.
Photorealistic visualizations, showing a good qualitative agreement with
anatomical images, suggest that the reconstructed surfaces are realistic and
detailed enough to be applicable in source analyses of auditory evoked fields.
PMID- 9644539
TI - [Perftoran--blood substitute with oxygen transport function].
PMID- 9644540
TI - [Resistance and capacitance of sural veins during electrical stimulation of
ventral regions of the medulla oblongata].
PMID- 9644541
TI - [Effect of simple proline-containing peptides on the functional activity of the
anticoagulant system and primary homeostasis].
PMID- 9644542
TI - [Peptide correction of disturbed relations in the central nervous system].
PMID- 9644543
TI - [The role of endogenous neuromodulator peptides in enhancement of the functional
tolerance of brain neurons to anoxia].
PMID- 9644544
TI - [Effect of human apolipoprotein A-I gene on vasoactive properties of high density
lipoproteins in rats of different age].
PMID- 9644545
TI - [The role of Thy 1.2(+)-cells in regulation of hematopoiesis during cytostatic
depression].
PMID- 9644546
TI - [Characteristics of peptide vagotropic effects during subtotal blockade of heart
M-cholinoreceptors].
PMID- 9644547
TI - [Effect of lamotrigine on development of neurogenic pain syndrome in rats].
PMID- 9644548
TI - [Comparative characteristics of cholinergic systems of the neocortex and
hippocampus of rats with low and high resistance to hypoxia].
PMID- 9644549
TI - [Effect of the intraperitoneal administration of spermine on oxidative processes
in isolated liver mitochondria of rats during hypothermia].
PMID- 9644550
TI - [Participation of oxygen free radicals in disturbance of restoration of the
aerobic metabolism of the transplanted heart with different periods of
conservation].
PMID- 9644551
TI - [Interaction of 16alpha,17alpha-cyclopropanoprogesterone with progesterone
receptor of the rat uterus].
PMID- 9644552
TI - [Contribution of genetic and individually acquired factors in morphine
sensitivity in WAG/G and Fischer-344 rats].
PMID- 9644554
TI - [Potentiation of the efficacy of anticonvulsant diazepam by electrostimulation of
the cerebellar cortex].
PMID- 9644553
TI - [Effect of calcium channel blocker nifedipine on anxiety and seizure
manifestations of abstinence syndrome in rats after withdrawal of long-term
diazepam administration].
PMID- 9644555
TI - [Anti-arrhythmia activity of befol, sufan, mexidol, and T3-146 in combination
with other anti-arrhythmia agents].
PMID- 9644556
TI - [Changes in parameters of nonspecific resistance of the body, humoral and
cellular immunity after acute acetonitrile intoxication].
PMID- 9644557
TI - [Characteristics of effects of mu-, delta-, and kappa-opioid agonists and
enkephalinase inhibitor RB101 in rats of two inbred strains].
PMID- 9644558
TI - [Differences in the composition of cellular elements of blood and lymphocyte
dehydrogenase activity in rats with genetic variability in neuroendocrine
status].
PMID- 9644559
TI - [Determination of steroid hormone receptors in different tissues and neoplasms].
PMID- 9644560
TI - [The role of glutathione and glutathione-S-transferase in neoplasm drug
resistance].
PMID- 9644561
TI - [Anticarcinogenic effect of palustran on development of tumors induced by 3-(1
alpha-L-arabinopyranosyl)-1-methyl-1-nitrosourea (AMNU) in rats].
PMID- 9644562
TI - [Effect of micronized fenofibrate (lipantyl-200M) on synthesis of cholesterol in
peripheral blood lymphocytes of patients with ischemic heart disease and
hyperlipidemia].
PMID- 9644563
TI - [The level of sex steroid receptors in the myometrium during cesarean section].
PMID- 9644564
TI - [Circadian and seasonal variations of the activity of blood lymphocyte
dehydrogenases during secondary immunodeficiency in women with acute inflammatory
gynecologic diseases of nonspecific etiology].
PMID- 9644565
TI - [Production of cultured human placental macrophages].
PMID- 9644566
TI - [Ultrastructure and proliferation of stomach epitheliocytes during ultraviolet
laser irradiation].
PMID- 9644567
TI - [Macrophages of the subcutaneous connective tissue during alpha-tocopherol
administration and dehydration].
PMID- 9644568
TI - [Effect of dextran infusions on destructive processes in the liver parenchyma
during long-term crush syndrome].
PMID- 9644569
TI - [Determination of antigens of anti-thrombocyte antibodies in patients with
different forms of thrombocytopenia].
PMID- 9644570
TI - A system for postoperative visualization and analysis of left ventricular
pressure-volume loops.
AB - A patient monitoring system for continuous real-time monitoring of left
ventricular (LV) function in the postoperative setting was developed. Common
hemodynamic parameters and LV functional indices are all calculated from left
ventricular pressure-volume loops (PV-loops). Visualization of the PV-loops,
along with the hemodynamic parameter derived from them, provides valuable insight
into ventricular function and patient recovery. The pressure component is
obtained via a pressure sensing catheter placed during surgery. Volume is
measured via non-imaging radionuclide techniques using a modified Capintec-VEST.
Following surgery and transfer to the recovery unit, the patient's blood is
labeled with Tc-99m. A portable gamma camera is used to measure baseline ejection
fraction (EF) and to aid in placing the VEST. The specific radioactivity of the
blood is calibrated using the baseline EF and thermodilution cardiac output. To
confirm the volume measurement accuracy of this technique six patients undergoing
bilateral heart catheterization were studied. Single-plane cineventriculographic
LV volumes were compared to those calculated from the VEST's time activity curve.
PMID- 9644571
TI - Performance evaluation of filtered backprojection reconstruction and iterative
reconstruction methods for PET images.
AB - The filtered backprojection (FBP) algorithm and statistical model based iterative
algorithms such as the maximum likelihood (ML) reconstruction or the maximum a
posteriori (MAP) reconstruction are the two major classes of tomographic
reconstruction methods. The FBP method is widely used in clinical setting while
iterative methods have attracted research interests in the past decade. In this
paper we studied the performance of the FBP, the ML and the MAP methods using
simulated projection data. The experiment showed that the MAP algorithm generated
superior image quality in terms of the bias, the variance, and the average mean
squared error (MSE) measures.
PMID- 9644572
TI - Regional cerebral blood flow determination using 133Xe and a standard rotating
gamma-camera.
AB - While most of the methods for quantitative regional cerebral blood flow (rCBF)
determination in man requires expensive fast devices, a method is proposed using
single photon emission computed tomography with a conventional rotating gamma
camera and 133Xe inhalation. It is tested using a computer simulation of a
cerebral exam and a simplified CBF map as a model. The results obtained show that
this method is relevant and can be tested in clinical studies.
PMID- 9644573
TI - A cluster computer system for the analysis and classification of massively large
biomedical image data.
AB - The current trend in medical image acquisition is towards the generation of image
datasets which are massively large, either because they exhibit fine x, y, or z
resolution, are volumetric, are multispectral, or a combination of all of the
preceding. Such images pose a significant computational challenge in their
analysis, not only in terms of data throughput, but also in terms of platform
costs and simplicity. In this paper we describe the role of a cluster of
workstations together with two quite different application programming interfaces
(APIs) in the quantitative analysis of anatomic image data from the visible human
project using an MRF-Gibbs classification algorithm. We describe the typical
architecture of a cluster computer, two API options and the parallelization of
the MRF-Gibbs procedure for the cluster. Finally, we show speedup results
obtained on the cluster and sample classifications of visible human data.
PMID- 9644574
TI - Detection of negative allosteric effects between monoclonal antibodies by using
an antigenic model-builder computer program.
AB - The ability of monoclonal antibodies (MAb) to bind or not simultaneously to the
antigen (Ag) is used to establish antigenic maps considering that two different
MAb do not bind to the Ag when the corresponding epitopes are overlapped (steric
effect). Nevertheless, MAb inducing negative allosteric effect on the Ag could
prevent the binding of the second MAb even if it is directed to a separate
epitope. We report here that a knowledge-based expert module included in our
previously described antigenic model-builder program (MAPAG) was able to
differentiate between steric and negative allosteric effects between some MAb.
PMID- 9644575
TI - An algorithm for the automatic differentiation between the speech of normals and
patients with Friedreich's ataxia based on the short-time fractal dimension.
AB - In this paper, we describe an algorithm, based on acoustic pattern matching
techniques, for providing an automatic, highly reliable distinction between
normal and some kind of pathological speech (Friedreich's ataxia disease). For
each utterance, the short-time fractal dimension parameter and, for comparison,
the zero-crossing and energy ratio parameters are evaluated and used in the
classification task by means of a dynamic programming procedure. Although all the
parameters are able to differentiate the two groups, the fractal dimension
parameter seems to provide a more reliable pattern classification than zero
crossing and energy ratio. Finally, we point out that, to the discrimination
purpose, an accurate choice of the utterances to be pronounced by the subjects is
to be considered.
PMID- 9644576
TI - [Possible modeling of neural networks in the framework of thermodynamics of
genetically disordered systems (glasses)].
PMID- 9644578
TI - [Immediate and long-term functional and morphological changes in the neuronal
structures of cerebral cortex of cats subjected to callosotomy].
PMID- 9644577
TI - [Interchangeability of growth factors in early G(0)-G(1) period of cell cycle].
PMID- 9644579
TI - [Nonmonotonous changes in erythrocyte sedimentation rate in whole blood].
PMID- 9644580
TI - [Conformation aspects of stereospecificity of acetylcholinesterase hydrolysis of
beta-methylcholine substrates].
PMID- 9644581
TI - [Cytogenetic changes in thymus and bone marrow cells after exposure to pulsed
infrared laser irradiation of locally irradiated mechanically damaged skeletal
muscle of rats].
PMID- 9644582
TI - [Response of rat skeletal muscle fibers and neuromuscular junction on strength
exercise training].
PMID- 9644583
TI - [Structural state of cell membranes in animal brain during development of
hyperbaric hyperkinesias].
PMID- 9644584
TI - [Topography and resolution of the retina in the dolphin Sotalia fluviatilus].
PMID- 9644585
TI - [Karyotype of siberian roe-deer (Capreolus pygargus Pall.) from the northern
border of the areal].
PMID- 9644586
TI - [Phylogenetic analysis of ORF1-containing mobile elements: identification of
evolutionary related groups].
PMID- 9644587
TI - [Alkaline phosphatase in the Drosophila melanogaster strain characterized by
differences in sexual behavior of males in normal and stressful conditions].
PMID- 9644588
TI - [Radioadaptive response and antimutagenic effect of interferon have common
pathways of cell protection against gamma radiation].
PMID- 9644589
TI - [Increased frequency of recombination exchanges controlled by RecA protein from
Pseudomonas aeruginosa].
PMID- 9644590
TI - Hydrodynamic properties of gelatin in dilute solutions.
AB - Aggregation properties of Gelatin chains in neutral aqueous solutions, are
reported in the temperature range T = 35-60 degrees C, from the measured
intrinsic viscosity [eta], diffusion coefficient, D(o), molecular weight Mw, and
radius of gyration (Rg) data. Gelatin chains doubled their size as the solution
was cooled to 35 degrees C from 60 degrees C. The intermolecular interaction was
found to be repulsive which showed significant decrease as the temperature was
reduced. The data provides excellent fitting to the scaling relations Mw[eta] =
(1.96 +/- 0.06) x 10(-26)(Re,eta/Re,D)3(D(o) eta o/T)-3 and (D(o)n1/2)-1
approximately equal to (6 1/2 pie eta o chi beta/kB/T)[1 + 0.201(v/beta 3)n1/2]
where n is the number of segments in the chain. The ratio of the hydrodynamic
radius (Re,D) (deduced from D(o)) and Rg, (Re,D/Rg = zeta) was found to be 0.555.
From the known solvent viscosity eta o, the segment length beta, was deduced to
be (15 +/- 2) A. The deduced excluded volume was v approximately equal to (4.1
A)3. The Flory-Huggins interaction parameter (zeta) did not show observable
temperature dependence.
PMID- 9644591
TI - Interactions of DNA with fluorescent dyes: by scanning tunneling microscopy.
AB - Genomic DNA was obtained from peripheral blood samples of healthy volunteers and
interacted with two fluorescent dyes (i.e. Hoechst 33,258 and ethidium bromide)
in aqueous media. These media containing DNA-dye complexes deposited on the gold
coated mica surfaces. Then, STM images were obtained in which the STM was
operated in air at atmospheric pressure with a tip-to-substrate bias voltage of
250-1000 mV (sample positive) and the tunneling currents in the range of 10-20 pA
by using etched tips of Pt/Ir, in constant current mode. Both dyes from molecular
clusters on DNA. While, the Hoechst molecules were observed on the DNA chains at
regular distances, the ethidium bromide molecular clusters did not.
PMID- 9644592
TI - Structural organisations of hemoglobin and myoglobin influence their binding
behaviour with phenothiazines.
AB - Binding modalities of chlorpromazine and trifluoperazine, two widely used
antipsychotic phenothiazine drugs with hemoglobin and myoglobin have been studied
to understand how the quaternary, tertiary and secondary structural organisations
of the proteins regulate the binding process. NaCl-induced alteration in the
quaternary structure of hemoglobin influences its binding modality with
phenothiazines. Minor alterations in the tertiary structure of thermally
denatured myoglobin (denaturation temperature ranging between 30-70 degrees C) do
not affect its affinity and the modality of binding with the drugs, but
alterations in the secondary structure of the protein denatured at temperatures
between 70-80 degrees C influence its binding.
PMID- 9644593
TI - Protein stability function relations: beta-lactoglobulin-A sulphydryl group
reactivity and its relationship to protein unfolding stability.
AB - The effect of protein stability on the reactivity of the free sulphydryl (SH)
group in beta-lactoglobulin-A (beta-LgA) provides a model for the study of
protein stability-function relations (PSFR). The free energy change for protein
unfolding (delta G(o)) and SH group exposure (delta GSH) were determined from (i)
the urea unfolding curve for beta-LgA and (ii) the kinetics of beta-LgA
SH/disulphide exchange with 2-pyridine disulphide (2-PDS) in 0-8 M urea (pH 3).
Protein unfolding profiles determined from extrinsic fluorescence and SH-group
reactivity measurements were not coincident. beta-LgA formed a stable
intermediate (X) state in the presence of 4 M urea with delta G(o) = 20 (+/-
0.03) kJ/mol. From the low rate of SH/disulphide exchange in 4 M urea, the SH
group within beta-LgA was efficiently masked within the X-state. SH reactivity
increased after beta-LgA was unfolded in 6-8 M urea with, delta GSH = 43(+/- 6.4)
kJ/mol. Such results are discussed in terms of possible interrelationships
between protein unfolding stability and SH reactivity in beta-LgA.
PMID- 9644594
TI - The phage lambda terminase enzyme: 1. Reconstitution of the holoenzyme from the
individual subunits enhances the thermal stability of the small subunit.
AB - The terminase enzyme from bacteriophage lambda is a hetero-trimeric complex
composed of the viral gpA and gpNu1 proteins (gpA1.gpNu1(2)) and is responsible
for packaging a single genome within the viral capsid. Current expression systems
for these proteins require thermal induction which may be responsible for the
formation of insoluble aggregates observed in E. coli. We report the re-cloning
of the terminase subunits into vectors which allow low temperature induction.
While this has resulted in increased solubility of the large gpA subunit of the
enzyme, the small gpNu1 subunit remains insoluble under all conditions examined.
This paper describes the solublization of gpNu1 with guanidinium hydrochloride
and purification of the protein to homogeneity. Reconstitution of the enzyme from
the individually purified subunits yields a catalytically-competent complex which
exhibits activity identical to wild-type enzyme. Thermal denaturation of the
proteins was monitored by circular dichroism (CD) spectroscopy and demonstrates
that while unfolding of gpA is irreversible, the gpNu1 subunit refolds into a
conformation which is essentially identical to the pre-heated protein. Moreover,
while denaturation of gpA is highly cooperative, the small subunit unfolds over a
wide temperature range and with thermodynamic parameters lower than expected for
a small globular protein. Thermally-induced denaturation of the enzyme
reconstituted from the individual subunits is highly cooperative with no evidence
of multiple transitions. Our data demonstrate that the terminase subunits
directly interact in solution, and that this interaction alters the thermal
stability of the smaller gpNu1 subunit. The implication of these results with
respect to assembly of a catalytically competent enzyme complex are discussed.
PMID- 9644595
TI - The phage lambda terminase enzyme: 2. Refolding of the gpNu1 subunit from the
detergent-denatured and guanidinium hydrochloride-denatured state yields
different oligomerization states and altered protein stabilities.
AB - The terminase enzyme from bacteriophage lambda is responsible for packaging a
single genome within the viral capsid. Gold and co-workers have developed a
scheme for the solubilization of the small terminase subunit (gpNu1) from
inclusion bodies using the strong detergent sarkosyl and purification of the
protein to homogeneity (gpNu1SRK) (Parris et al., J Biol Chem 1994;269:13564
13574). We have developed a similar purification scheme except that guanidinium
hydrochloride was used to denature the insoluble protein (gpNu1GDN). The circular
dichroism (CD) spectra of both protein preparations suggest that they are
predominantly alpha-helical when purified and stored in Tris buffers. Moreover,
thermal denaturation of the proteins thus purified yielded similar thermodynamic
parameters for unfolding (T(m), delta Hm and delta Sm of unfolding of
approximately 306 K, approximately 22 kcal/mol and approximately 70 cal/mol.K,
respectively). Interestingly, however, when the proteins were purified and stored
in imidazole buffers, the gpNu1SRK preparation lost a significant amount of
secondary structure and was more stable to both thermally-induced and guanidinium
HCl-induced denaturation than was gpNu1GDN. The purified gpNu1 monomers
oligomerize into apparent tetramers and hexamers in solution and the distribution
between these two oligomeric states and into higher order aggregates depends upon
buffer composition, salt concentration and protein concentration. Moreover,
differences in the oligomerization state of gpNu1SRK and gpNu1GDN under identical
buffer conditions were observed. The significance of these results with respect
to the biological role of the phage lambda gpNu1 protein are discussed.
PMID- 9644596
TI - Laser-Raman and FT-IR spectroscopic studies of peptide-analogues of silkmoth
chorion protein segments.
AB - Silkmoth chorion, the proteinaceous major component of the eggshell, with
extraordinary mechanical and physiological properties, consists of a complex set
of proteins, which have a tripartite structure: a central, evolutionarily
conserved, domain and two more variable 'arms'. Peptide-analogues of silkmoth
chorion protein central domain segments have been synthesized. Laser-Raman and
infrared spectroscopic studies suggest the preponderance of antiparallel beta
pleated sheet structure for these peptides, both in solution and in the solid
state.
PMID- 9644597
TI - Radiation crosslinking of a bacterial medium-chain-length poly(hydroxyalkanoate)
elastomer from tallow.
AB - Pseudomonas resinovorans produces a medium-chain-length poly(hydroxyalkanoate)
(MCL-PHA) copolymer when grown on tallow (PHA-tal). This polymer had a repeat
unit composition ranging from C4 to C14 with some mono-unsaturation in the C12
and C14 alkyl side chains. Thermal analysis indicated that the polymer was semi
crystalline with a melting temperature (T(m)) of 43.5 +/- 0.2 degrees C and a
glass transition temperature (Tg) of -43.4 +/- 2.0 degrees C. The presence of
unsaturated side chains allowed crosslinking by gamma-irradiation. Irradiated
polymer films had decreased solubility in organic solvents that indicated an
increase in the crosslinking density within the film matrix. The addition of
linseed oil to the gamma-irradiated film matrix enhanced polymer recovery while
minimizing chain scission. Linseed oil also caused a decrease in the enthalpy of
fusion (delta Hm) of the films (by an average of 60%) as well as enhanced
mineralization. The effects of crosslinking on the mechanical properties and
biodegradability of the polymer were determined. Radiation had no effect on the
storage modulus (E') of the polymer. However, radiation doses of 25 and 50 kGy
did increase the Young modulus of the polymer by 129 and 114%, and the tensile
strength of the polymer by 76 and 35%, respectively. Finally, the formation of a
higher crosslink density within the polymer matrix decreased the biodegradability
of the PHA films.
PMID- 9644598
TI - A structural study of beta-casein adsorbed layers at the air-water interface
using X-ray and neutron reflectivity.
AB - New details on the structure of beta-casein adsorbed layers, at the air-water
interface, have been obtained using X-ray and neutron reflectivity. The
experimental data are fitted well by a power law model and the results discussed
in terms of the distribution of amino-acid sequences between trains, loops and
tails. This distribution seems to be consistent with statistical theories
established for flexible polymers. The trains are present in close proximity to
the surface as a dense layer 8-9 A thick. At low surface coverage, the tail
effect is negligible and the adsorbed layer is composed of nearly 60% amino-acid
sequences in trains and the remaining in loops. When the bulk concentration is
increased, a substantial part of the amino-acid residues has to be accommodated
in loops and long tails; the adsorbed layer becomes more extended (80-100 A). A
striking feature is observed for a high bulk concentration (10(-1) wt.%): trains
are forced to eject out of the interface.
PMID- 9644599
TI - [Antimicrobial activity of macrolides against clinical isolates].
AB - Antimicrobial activity of 6 macrolides was determined using a micro-broth
dilution method, against 535 clinical isolates of 22 species, which were isolated
in 1996 from 325 facilities in Japan. Results were as follows. 1. In general,
antimicrobial activities of 14-membered macrolides were higher than those of 16
membered macrolides. The antimicrobial activities of 14-membered macrolides were
in the order of clarithromycin (CAM), erythromycin (EM), roxithromycin (RXM).
Among 16-membered macrolides, rokitamycin (RKM) was the most potent, josamycin
(JM) was next potent followed by midecamycin (MDM). More numbers of highly
resistant strain of > 100 micrograms/ml were recognized in 14-membered macrolides
than in 16-membered macrorides. 2. Most of S. pyogenes (group A) strains were
distributed in the susceptible range and almost none was found in the resistant
range. 3. S. pneumoniae strains were distributed widely from the susceptible
range to the highly resistant range, and as high as 37.1% fell into the high
resistance of > 100 micrograms/ml range. 4. Against Peptostreptococcus spp. and
MRSA, 16-membered macrolides were more effective than 14-membered macrorlides,
and their antibacterial activities were in the order of RKM, JM, MDM. Ratio of
high-resistant strains of > 100 micrograms/ml against 14-membered macrolides was
much higher than that against 16-membered macrolies. 5. Most of M. (B.)
catarrhalis strains were distributed in the susceptible range of < or = 1.56
micrograms/ml, and most of H. influenzae strains were distributed within the
moderately resistant and the resistant ranges. 6. In M. (B.) catarrhalis and H.
influenzae, no correlation between macrolide resistance and beta-lactamase
production was recognized. 7. Most of C. jejuni strains were susceptible to all
macrolides used in this study.
PMID- 9644600
TI - [Increase of non-amidated muropeptides in the cell wall of vancomycin-resistant
Staphylococcus aureus (VRSA) strain Mu50].
AB - The mechanism of resistance was studied with vancomycin-resistant Staphylococcus
aureus (VRSA) strain Mu50. It was demonstrated that the incorporation of 14C-N
acetylglucosamine into the cell wall of Mu50 was not suppressed in the presence
of 8 microliters/ml of vacomycin, whereas it was completely suppressed in
vancomycin-susceptible strains FDA209P and H-1. Increased binding of vancomycin
to the wall of Mu50 was observed compared to the control strains: 1.7 x 10(16)
(Mu50), 6.1 x 10(15) (209P), and 6.7 x 10(15) (H-1) vancomycin molecules/mg cell
wall, respectively. Remarkable proportion of the cell-wall component muropeptides
were non-amidated in the cell wall of Mu50. In concordance with this phenomena,
peptidoglycan cross-linkage decreased strikingly in the Mu50 strain. Free D-Ala-D
Ala residues at the end of muropeptides in the pre-existing cell wall generated
by decreased cross-linkage seems to account for increased vancomycin binding. The
increase of vancomycin-resistance level is presumably caused by sequestration of
vancomycin molecules from primary target point on cell membrane. It was
considered that at least two phenotypic changes are required for the vancomycin
resistance in the Mu50 strain. First, as we have described previously, is the
activated cell wall synthesis, and second, the reduction of cross-linkage of
peptidoglycan by production of non-amidated muropeptide precursors.
PMID- 9644601
TI - [Drug susceptibility of clinically isolated Helicobacter pylori].
AB - Between January 1995 and March 1997, 78 Helicobacter pylori strains were isolated
from patients with gastritis and gastric ulcer and their drug-susceptibilities to
8 antimicrobial agents and 3 anti-ulcer drugs were determined. Imipenem was the
most active agent and its MICs to all the strains tested were lower than 0.013
microgram/ml. Amoxicillin, cefaclor and minocycline were active against H. pylori
with MIC90s of 0.05 microgram/ml, 0.78 microgram/ml and 0.39 microgram/ml,
respectively, and no resistant strains against these drugs were isolated.
However, resistant strains to clarithromycin (isolation frequency: 9%),
erythromycin (13%), ofloxacin (8%) and metronidazole (13%) were isolated. Triple,
double and single resistant strains to above 4 antimicrobial agents were noted.
No quadruple resistant strain was isolated. Frequencies of those resistance
patterns were 14.3% (triple), 28.6% (double), and 57.1% (single), respectively.
Seven erythromycin-resistant strains were shown to be cross-resistant to
clarithromycin but 3 erythromycin-resistant strains were susceptible to
clarithromycin. It seems likely that this phenomenon is caused by the fact that
clarithromycin is more active to H. pylori than erythromycin. The MIC90 value of
lansoprazole was lower than those of omeprazole and famotidine.
PMID- 9644602
TI - [Clinical and bacteriological studies on panipenem/betamipron in pediatrics.
Kanagawa Research Group for Infectious Diseases of Children].
AB - Following its introduction into the market, PAPM/BP (panipenem/betamipron) was
clinically studied in 188 evaluable cases out of 207 cases primarily of
respiratory infectious diseases treated at the pediatric departments of 15
hospitals. In the clinical evaluation, the drug proved effective in three of
three cases of sepsis; three of three cases of suppurative meningitis; nine of
ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63
cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of
phyothorax, all of which are respiratory infectious diseases; one of one case of
secondary infection of a chronic respiratory disease; and two of two cases of
lymphadenitis, which is a disease of the soft dermal structure. The overall
efficacy rate was 91.0% (171/188 cases). In the bacteriological study, Gram
positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31
strains of S. pneumoniae (96.8%), and three of three strains of S. pyogenes.
Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae
(88.2%), three of four strains of M. catarrhalis, and two of two strains of K.
pneumoniae. The overall elimination rate was 92.1% (70/76 strains). In the 23
strains of S. pneumoniae that were examined, penicillin-resistant strains
accounted for 56.5%, showing an elimination rate of 100%. No serious adverse
effects were observed, and the incidence of adverse effects was 1.45%. As for
abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases
(3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case
(0.51%). These results suggest that PAMP/BP could be considered the first choice
in the treatment of infectious diseases in pediatrics, due to its effectiveness
and high level of safety.
PMID- 9644603
TI - [Clinical evaluation of combination therapy with cefpirome and amikacin for
infections associated with hematological disorders].
AB - Cefpirome (CPR) and amikacin (AMK) were used concomitantly to treat infections
complicated by hematological diseases. A total of 100 subjects were evaluated,
and the allover efficacy rate was 72.0%. Acute leukemia was found in the largest
number of patient, 55, followed by 12 cases of malignant lymphoma and 6 cases of
chronic myelogenous leukemia. By type of infection, patients having suspected
sepsis were the largest in number, being 50, and the efficacy rate was 68.0%. The
efficacy rates for sepsis and pneumonia were 57.1% (7 cases) and 61.1% (18
cases), respectively. The efficacy rates by neutrophil counts before
administration of CPR and AMK and at 7 days after administration were both 71.9%
in the group of less than 500/microliter, both 60.0% in the group of less than
100/microliter. The efficacy rate was 75.0% in the group of granulocyte colony
stimulating factor (G-CSF) concomitant usage, and 70.0% in the non-concomitant
usage group. Concomitant treatment with CPR and AMK exhibited a high level of
safety and efficacy rates in infections complicated by hematological diseases and
high.
PMID- 9644604
TI - Native American adolescents' views of fetal alcohol syndrome prevention in
schools.
AB - Alcohol is the most commonly abused substance among adolescents in the United
States. Adolescent females are recognized as one group at risk for giving birth
to babies with fetal alcohol syndrome (FAS). Sixth through eighth grade Native
Americans were surveyed about their attitudes toward and knowledge of FAS risk
factors and prevention strategies. Data revealed that 52% of students drank
alcohol prior to the survey. Though sexually active, students lacked knowledge
about the relationship between alcohol and FAS. The study revealed 1) limited
prevention programs in middle schools and 2) the most influential factor in
determining attitudes and decisions about alcohol use was the immediate family.
Students felt FAS prevention is an important topic in school health education,
noting the important role peers play in teaching and role modeling. Various
strategies incorporating music and communication technology such as videotape and
computer-assisted interactive tools into prevention materials are discussed.
PMID- 9644605
TI - Trends in tobacco use among high school students in the United States, 1991-1995.
AB - This study examined demographic characteristics of tobacco-using high school
students in the United States from 1991 through 1995. Data about cigarette
smoking and smokeless tobacco use among adolescent were collected in 1991, 1993,
and 1995 using the Youth Risk Behavior Survey, part of the Youth Risk Behavior
Surveillance System implemented by the Centers for Disease Control and
Prevention. Data indicated current smoking increased 26.5% from 1991 to 1995 with
one-third [31.2% (+/- 1.7)] of ninth grade students and 38.2% (+/- 3.5) of 12th
grade students reporting current smoking in 1995. Smokeless tobacco use remained
stable with 11.4% (+/- 1.7) of all students and one-fourth [25.1% (+/- 3.0)] of
White male students reporting smokeless tobacco use in 1995. Many students
already have begun using tobacco before reaching high school. Thus, interventions
should begin well before high school to prevent adolescents from using and
becoming addicted to tobacco.
PMID- 9644606
TI - AIDS risk among students attending Seventh-day Adventist school, in North
America.
AB - In 1995, a survey was conducted among students attending 69 Seventh-day Adventist
(SDA) high schools within the United States and Canada. The survey assessed the
extent that these students practiced sexual and drug-use behaviors which place
them at risk for contracting or transmitting the human immunodeficiency virus
(HIV). A total of 1,748 respondents enrolled in grades 9 through 12 completed
questionnaires similar to the instrument used in the 1993 Youth Risk Behavior
Survey (YRBS). Data were collected and compared to results from the 1993 YRBS.
Students who attended SDA parochial schools reported lower rates of sexual
intercourse compared to YRBS school counterparts (16.3% vs. 53.1%) and lower
rates of all substances measured. Furthermore, respondents were more likely to
engage in substance use and sexual intercourse if they had at least one parent
who used tobacco, alcohol, or marijuana, as reported by the students.
PMID- 9644607
TI - From eradication to resistance: five continuing concerns about pediculosis.
AB - A school nurse, serving in the capacity of infection control officer, is
responsible for managing head lice infestations. The nurse's concerns on the
student and parent levels include dispelling misconceptions about lice,
screening, motivating correct treatment, and providing follow-up. The nurse's
responsibility to the community as a whole also involves putting into practice
policies that prevent the spread of infestations without promoting pediculicide
resistance.
PMID- 9644608
TI - Cumulative effects of prevention education on substance use among 11th grade
students in Ohio.
AB - This article examines participation in school-based prevention activities from a
statewide sample of 11th grade students in Ohio. About 42% of subjects indicated
they had never been involved in a prevention education activity. Differences
existed in mean number of activities by both gender and White/nonWhite status.
Popular prevention education activities included participation in D.A.R.E. (Drug
Abuse Resistance Education) at elementary, junior high, and senior high levels,
"Just Say No Clubs"; Quest; and Red Ribbon Week. Only a small proportion of youth
participated exclusively in any one of these activities. An association existed
between student participation in prevention education and level of drug
involvement. Students in each activity had lower mean scores for drug involvement
when compared to students who had never participated in a prevention education
activity. Also, the lowest mean scores occurred among students who had
participated in multiple prevention activities.
PMID- 9644609
TI - Identifying sources of social support.
PMID- 9644610
TI - The PREPARE approach to training clinicians in school mental health programs.
PMID- 9644612
TI - How asthma friendly is your school? National Heart, Lung, and Blood Institute.
National Asthma Education and Prevention Program. School Asthma Education
Subcommittee.
PMID- 9644611
TI - Technology and the gender gap.
PMID- 9644613
TI - Long-term versus short-term hearing aid benefit.
AB - This study compared hearing aid benefit obtained 6 weeks and a minimum of 1 year
after fitting to determine if changes occurred over time. Fifteen individuals
with mild-to-moderate sensorineural hearing losses, who were successful users of
linear amplification, were fitted binaurally with the Resound BT2 Personal
Hearing System. These hearing aids are programmable in two frequency bands that
provide wide dynamic range compression (WDRC) amplification. The manufacturer's
recommended loudness growth in octave bands (LGOB) and audiogram programming
algorithm and fitting procedures were used. Following an initial 6-week period
and again following a minimum of 1 year of use, the Profile of Hearing Aid
Benefit (PHAB) was administered. Similarly, speech recognition performance was
tested using the Connected Speech Test (CST) in a six-talker speech babble at 50
dBA, +10 signal-to-noise (S/N); 60 dBA, +5 SNR; and 70 dBA, +2 SNR; and in quiet
with a reverberation time of 0.78 seconds. Significant aided benefit was shown.
These short-term benefit scores for the PHAB and CST were compared with those
obtained after 1 year of full-time use. Results revealed no significant change in
hearing aid benefit with long-term use, suggesting that a 6-week acclimatization
period is sufficiently long for clinical trials of this type of WDRC
amplification.
PMID- 9644614
TI - Contralateral suppression of distortion product otoacoustic emissions in children
with cystic fibrosis: effects of tobramycin.
AB - The role of the medial efferent system in altering and/or regulating outer hair
cell function in the mammalian cochlea has been proposed by a number of
investigators. This study measured contralateral suppression of distortion
product otoacoustic emissions (DPOAEs) in cystic fibrosis (CF) patients, treated
for lung infections with low to moderate cumulative doses of tobramycin, to
ascertain the contributions of the efferent-based mechanisms in the development
of ototoxicity. The results showed significant suppression of DPOAEs in
tobramycin-treated children compared to both nondrug-treated CF and normal
children of similar ages. Since DPOAE amplitudes were comparable across the drug
treated and control groups of subjects, pronounced DPOAE suppression in the drug
treated group may be attributed to the instability of the cochlear amplifier
induced by the tobramycin treatment. These findings also suggest that enhanced
contralateral suppression may be the first sign of a developing ototoxicity.
PMID- 9644615
TI - Vowel perception in prelingually deafened children with multichannel cochlear
implants.
AB - Vowel perception ability for 16 prelingually deafened children using Nucleus 22
channel cochlear implants was studied at 12, 24, and 36 months postimplantation.
Information transmission analysis was used to evaluate the effectiveness of the
implants in conveying the essential cues required for accurate vowel
identification and whether the cues used varied with experience or device use.
Individual vowel identification varied widely with mean scores significantly
improving between 12 and 24 months but not between 24 and 36 months. Information
transmission scores for all vowel features (fronting, height, duration, and
diphthongization) increased dramatically between 12 and 36 months. Results
indicated that vowel height and vowel fronting were the most salient features for
the subject group. There were no differences in the pattern of confusions made
across test sessions or across groups when divided into "poor" and "good" users.
However, there was evidence that the "good" users made better use of higher
frequency formant information than the "poor" users. The results of the present
study add to the accumulation of evidence pointing to the great benefit that
cochlear implantation can provide to prelingually deafened children. Overall
performance for the vowel recognition test used in this study was quite high and
analysis of the childrens' errors suggested that their cochlear implants were
reasonably effective at conveying the most essential spectral information
required for vowel discrimination.
PMID- 9644616
TI - Aging and word recognition in competing message.
AB - As part of an epidemiologic study of hearing disorders in older adults, word
recognition performance (NU-6 word lists in quiet and in competing message) was
evaluated for 3189 adults grouped by age (48-59 years, n = 1176; 60-69 years, n =
979; 70-79 years, n = 794; 80-92 years, n = 240). Overall, scores for all
measures were worse for older age groups and worse for men than for women. Word
recognition scores in competing message were poorer than word recognition scores
in quiet for all subjects and age groups. Further, differences in scores across
age groups and gender were greater for the word recognition test in competing
message than for the word recognition test in quiet. Although degree of hearing
loss accounted for the largest portion of variation in word recognition scores,
the observed age and gender differences remained significant after adjusting for
the degree of sensorineural hearing loss.
PMID- 9644617
TI - Recognition of temporally distorted words by listeners with and without a
simulated hearing loss.
AB - In separate experiments, word recognition performance of two groups of 12 normal
hearing young adults was investigated as a function of temporal distortion (i.e.,
time compression ratio or reverberation time) with and without a simulated high
frequency hearing loss (i.e., low-pass filtered at 2000 Hz). Performance
decreased significantly as a function of increasing time compression,
reverberation, and with the simulated hearing loss (p < .05). A statistically
significant interaction between each of time compression ratio and reverberation
time with the filtered listening condition was found (p < .05). This finding of
an interactive, as opposed to a simple additive, effect of multiple distortions
of the speech on word recognition performance suggests that loss of audibility
alone cannot account for decrements in word recognition performance with time
altered speech. It is suggested that this multiplicative effect for combined
acoustic distortions is a consequence of the functional loss of the high
frequency region of the cochlea. Not only is there a loss of audibility, but
there is also a loss in temporal resolution capacity since it is perception
mediated through the population of high-frequency auditory channels that has the
best temporal resolution.
PMID- 9644618
TI - Reliability of the Contour Test in a population of adults with hearing loss.
AB - With the increasing popularity of hearing aids with wide dynamic range
compression, where the goal may be to restore normal perception of loudness,
there has been renewed interest in obtaining individual loudness judgments in a
clinically feasible, reliable manner as part of the hearing aid evaluation. The
purpose of the current investigation was to evaluate the test-retest reliability
of the Contour Test of Loudness Perception. Twenty-seven adults with hearing loss
participated in the experiment. They produced loudness judgments on two separate
occasions. Results as assessed by the intraclass correlation statistic revealed
that the Contour Test has adequate consistency and absolute agreement across
frequency and loudness categories over two test sessions separated in time.
Results are discussed in relation to previous reliability findings from other
loudness judgment methods and other subject populations.
PMID- 9644619
TI - Procedural considerations in the real-ear measurement of completely-in-the-canal
instruments.
AB - Conventional procedures for measurement of the real-ear aided response (REAR) of
hearing aids are performed by placing the probe tube 5 mm beyond the medial tip
of the canal portion of the earmold or shell and within 5 mm of the tympanic
membrane. Completely-in-the-canal (CIC) instruments insert more deeply into the
ear canal, and thus may make adherence to conventional probe-microphone
procedures impossible. The REAR was measured at several probe tube insertion
depths, using two insertion methods: through a probe vent and alongside the CIC
shell. Results indicated that conventional probe insertion depth is not necessary
for CIC instruments and may place some clients at risk for discomfort due to
contact of the probe tube with the tympanic membrane. Placement of the probe tube
along-side the CIC shell rather than through a probe vent resulted in slit leak
venting effects that were highly variable across subjects. A probe tube placement
protocol for use with CIC instruments is suggested.
PMID- 9644620
TI - A FIT solution.
AB - The Fusion at Inferred Threshold (FIT) test is a clinically useful procedure for
assessing air-conduction pure-tone thresholds in any ear that may not be tested
by conventional procedures with masking. It has not been widely reported in the
literature. This article describes the FIT test procedure and provides four case
studies where the FIT was used successfully to determine appropriate management
strategies.
PMID- 9644621
TI - Reliability issues with the Synthetic Sentence Identification test.
AB - This investigation examined the reliability of the Synthetic Sentence
Identification (SSI) test. An adaptive procedure was used to assess speech
recognition thresholds (SRTs) for the SSI lists over two separate test sessions.
The commercially available Davy Crockett passage and a multitalker babble were
used as competition. Subjects consisted of 20 adults with normal hearing
sensitivity. Results indicated (1) significantly higher SRTs with the multitalker
babble, (2) significant differences in SRTs among SSI lists when using the Davy
Crockett competition, (3) no significant learning/practice or fatigue effects
across trials in either noise condition, and (4) high test-retest reliability
across test sessions. Clinical implications of these data are considered.
PMID- 9644622
TI - Auditory and auditory-visual recognition of clear and conversational speech by
older adults.
AB - Research has shown that speech articulated in a clear manner is easier to
understand than conversationally spoken speech in both the auditory-only (A-only)
and auditory-visual (AV) domains. Because this research has been conducted using
younger adults, it is unknown whether age-related changes in auditory and/or
visual processing affect older adults' ability to benefit when a talker speaks
clearly. The present study examined how speaking mode (clear vs conversational)
and presentation mode (A-only vs AV) influenced nonsense sentence recognition by
older listeners. Results showed that neither age nor hearing loss limited the
amount of benefit that older adults obtained from a talker speaking clearly.
However, age was inversely correlated with identification of AV (but not A-only)
conversational speech, even when pure-tone thresholds were controlled
statistically.
PMID- 9644623
TI - Effects of two repair strategies on speechreading of words and sentences.
AB - The effectiveness of two repair strategies, repetition and paraphrasing, in
enhancing speechreading performance was evaluated on 20 young adults with normal
hearing using both word and sentence test stimuli. Both strategy types produced
significant improvement, and the repeat strategy yielded the greatest gains
overall. Paraphrasing resulted in the most enhancement for words, while
repetition was the most effective of the two strategies with sentences. The
inclusion of both repair strategies is recommended in communication therapy with
the hearing impaired.
PMID- 9644624
TI - Effect of volume expansion on the paracellular flux of lanthanum in the proximal
tubule.
AB - Although studies of volume expansion (VE) in the Necturus suggest a major role
for paracellular flux in reabsorption by the proximal tubule, results from
morphologic or electrophysiologic studies of the effect of VE on the rat proximal
tubule suggest only a minor role for paracellular transport. In the present
study, during in vivo microperfusion, lanthanum was used as an extracellular
marker to determine bidirectional paracellular flux in the rat proximal tubule
before and during 10% VE. Lanthanum itself did not affect proximal tubule
reabsorption (delta 0.7 +/- 3.3 nl/min, LaCl3 versus saline infusion, n = 7).
When lanthanum was added to the luminal perfusate, paracellular lanthanum efflux
from the lumen to the interstitium was 28.9 +/- 6.6 pg/min per mm, n = 7.
Subsequent VE significantly decreased the paracellular lumen-to-interstitium
efflux to 12.8 +/- 8.3 pg/min per mm concomitant with a 49% decrease in proximal
fluid reabsorption (delta -2.6 +/- 0.9 nl/min per mm, P < 0.05). When lanthanum
was infused interstitially, by means of a chronically implanted matrix, there was
significant paracellular lanthanum influx from the interstitium into the lumen
(143.9 +/- 18.6 pg/min per mm, n = 4). Subsequent VE significantly increased this
interstitium-to-lumen influx to 212.1 +/- 29.2 pg/min per mm as proximal
reabsorption was significantly decreased by 58% (delta -2.8 +/- 0.8 nl/min per
mm, P < 0.05). Thus, VE affects bidirectional paracellular flux in a manner that
would decrease proximal reabsorption; paracellular efflux from the lumen to the
interstitium was decreased, whereas paracellular influx from the interstitium to
the lumen was increased.
PMID- 9644625
TI - Biochemical and ultrastructural characterization of fluid transporting LLC-PK1
microspheres.
AB - The established renal epithelial cell line LLC-PK1 (proximal tubule) started to
form multicellular spheroids within 24 h when grown in agar overlay culture. The
spheroids, average diameter 100 to 350 microns, were free-floating with a
butterfly-like structure due to the formation of several hollow microspheres. The
microspheres were lined with polarized epithelial cells that had an abundance of
microvilli protruding into the external medium and a well developed vacuolar
apparatus, including coated pits, endocytotic vacuoles, and lysosomes. The
microspheres were sealed between lumen and the surrounding medium by tight
junctions and fluctuated in size due to fluid being transported in an apical-to
basal direction. Vasopressin was found to stimulate this transport, whereas the
addition of ouabain or HgCl2 inhibited both spheroid growth and fluctuation in
size with time. Biochemical assays of brush-border and lysosomal marker enzymes
demonstrated an increase in enzyme activity during spheroid formation and growth.
The most dramatic changes were observed for dipeptidyl peptidase IV (two- to
threefold after 1 d and 53.5-fold after 15 d), reflecting the cellular
polarization and brush-border formation during spheroid formation. When the
typical lysosomal enzymes were compared, the activity of peptide bond splitting
enzymes increased earlier than others. In conclusion, LLC-PK1 spheroids capable
of forming microspheres represent an in vitro manifestation of specialized
epithelial properties maintained in cell culture, thus providing a tool for
studying renal physiologic mechanisms at a cellular level.
PMID- 9644626
TI - Renal endothelin system in polycystic kidney disease.
AB - Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and
formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst
formation were also seen in human endothelin-1 (ET-1) transgenic mice. This
study, therefore, analyzes the tissue distribution of ET-1, the tissue
concentrations of ET-1, as well as the expression of ET receptor subtypes in the
kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+)
and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and
the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were
analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor
antagonist bosentan on hemodynamic and renal function were investigated in 6-mo
old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected
rats showed significantly elevated tissue levels of ET-1 compared with age
matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2
fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001)
due to a highly increased ET-1 synthesis within the epithelial cells of the
cysts. Analyzing tissue sections from patients with typical autosomal dominant
PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts
as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor
density in all groups of affected rats. The acute blockade of both endothelin
receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a
significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and
GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased
(+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on
MAP, GFR, and RBF in age-matched controls. These data show that the paracrine
renal endothelin system is activated in PKD and participates in the regulation of
MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.
PMID- 9644627
TI - cDNA cloning and expression of a novel family of enzymes with calcium-independent
phospholipase A2 and lysophospholipase activities.
AB - Previous studies have suggested that activation of calcium-independent PLA2
(CaIPLA2) is an early event in cell death after hypoxic injury in proximal tubule
cells. An approximately 28-kD CaIPLA2 with preferential activity toward
plasmalogen phospholipids has been recently purified from rabbit kidney cortex
(D. Portilla and G. Dai, J Biol Chem 271, 15,451-15,457, 1996). Their report
describes the cloning of a full-length rat cDNA encoding CaIPLA2, using sequences
derived from the purified rabbit kidney cortex enzyme. In addition, cDNA from
rabbit kidney that encode the rabbit homologue of the enzyme and a closely
related isoform were isolated. The rat cDNA is predicted to encode an
approximately 24-kD protein, and each cDNA contains the sequence G-F-S-Q-G, which
fits the active site consensus sequence G-X-S-X-G of carboxylesterases. Several
lines of evidence (DNA sequence comparison, Southern blot analysis, and
examination of the expressed sequence tag database) show that CaIPLA2 enzymes are
encoded by a multigene family in rats, mice, rabbits, and humans. Northern
analysis of various tissues from the rat indicated that the CaIPLA2 gene is
ubiquitously expressed, with highest mRNA abundance observed in the kidney and
small intestine. The rat CaIPLA2 cDNA, when expressed in a baculovirus expression
system, and the purified rabbit kidney cortex protein exhibit both CaIPLA2 and
lysophospholipase activities. The cloned CaIPLA2 cDNA are expected to aid in
understanding the role of CaIPLA2 in cell death after hypoxic/ischemic cell
injury.
PMID- 9644628
TI - IL-4 and IL-13 augment cytokine- and CD40-induced RANTES production by human
renal tubular epithelial cells in vitro.
AB - Local production of cytokines by infiltrating monocytes/macrophages and Th1 and
Th2 cells is of importance in renal allograft rejection. Activated Th1 cells can
produce interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and tumor necrosis
factor (TNF), whereas Th2 cells produce IL-4 and IL-13, which inhibit Th1 cells.
Furthermore, activated T cells express the costimulatory molecule CD40-ligand.
During renal allograft rejection, the chemokine RANTES is detected in both
infiltrating mononuclear cells and tubular epithelium. It has been shown
previously that stimulation of proximal tubular epithelial cells (PTEC) with
cytokines or CD40-ligand results in production of RANTES. The present study
investigates the influence of Th1 and Th2 cytokines on RANTES production by
activated PTEC. RANTES was not detectable in supernatants of human PTEC
stimulated with IL-2, IL-4, IL-10, or IL-13 alone. Likewise, combination of these
cytokines with IL-1 alpha, IFN-gamma, or TNF-alpha, respectively, did not result
in detectable RANTES production. IL-2 and IL-10 had no significant effect on
RANTES production by activated PTEC. IL-4 or IL-13 in combination with IL-1 alpha
+ IFN-gamma or IFN-gamma + TNF-alpha resulted in a two- to fourfold augmentation
of RANTES production, ranging from 2.2 +/- 0.2 to 35 +/- 2 ng/ml in different
cell lines. CD40-activated PTEC stimulated with IL-4 or IL-13 produced six to ten
times more RANTES (ranging from 7.9 +/- 1.9 to 62 +/- 3.5 ng/ml in different cell
lines) compared with CD40-activated cells alone. Because RANTES production is
augmented by IL-4 and IL-13, this study suggests that during rejection, direct
cellular contact between activated Th2 cells and tubular epithelial cells
amplifies the local inflammatory reaction in the kidney.
PMID- 9644629
TI - Interleukin-15, a leukocyte activator and growth factor, is produced by cortical
tubular epithelial cells.
AB - Many renal diseases, including transplant rejection, are mediated by mononuclear
cells. Interleukin-15 (IL-15) has been recently described as a cytokine with IL-2
like activity. IL-15 is an effective leukocyte growth factor, activator, and
chemoattractant. In rejected human kidney allografts, elevated IL-15, but not IL
2, mRNA is expressed, suggesting a role for IL-15 in the rejection process. The
aim of this study was to investigate whether human cortical tubular epithelial
cells (HTC) are able to produce IL-15 and whether IL-15 expression is regulated
by inflammatory mediators. HTC were isolated and characterized, and IL-15
expression was analyzed by reverse transcription-PCR, enzyme-linked immunosorbent
assay, and bioactivity. It was found that HTC constitutively express IL-15. Upon
stimulation of HTC with interferon-gamma (IFN gamma), the levels of both mRNA and
protein increased up to twofold. In contrast, lipopolysaccharide, IL-1, IL-2, and
tumor necrosis factor-alpha had no detectable effect. IFN gamma action on HTC was
dose-dependent from concentrations of 5 U/ml, reaching a plateau at 50 U/ml. HTC
supernatants induced proliferation of the T cell line CTLD, which could be
partially blocked (50%) by specific IL-15 antibodies. This study shows that IL-15
is secreted by HTC and that the Th1-cytokine IFN gamma upregulates IL-15
expression. This suggests that HTC play a role in cell-mediated renal diseases by
releasing IL-15.
PMID- 9644630
TI - Upregulation of renal and systemic cyclooxygenase-2 in patients with active lupus
nephritis.
AB - In lupus nephritis (LN), renal thromboxane A2 (TXA2) production is increased, and
inhibition of TXA2 activity improves renal function. In patients with LN, renal
function depends very much on vasodilatory prostaglandins, and indeed inhibiting
the prostaglandin-forming enzyme cyclooxygenase (COX) with aspirin or related
compounds was detrimental on renal hemodynamics in these patients. There are no
data so far on whether the excessive TXA2 production in LN derives from
upregulation of type I or type II isoforms of COX. It was found that TXB2
synthesis and COX-2 gene expression were higher in peripheral blood mononuclear
cells from patients with active LN compared to patients in the inactive form of
the disease and to healthy subjects. Unlike COX-2, levels of COX-1 mRNA were
comparable in lupus patients and control subjects and were not influenced by the
disease activity. Immunoperoxidase studies on kidney biopsies showed COX-1
staining in glomerular arterioles and other renal vessels, with no evident
difference between lupus biopsies and control specimens taken from either
individuals who were free of renal disease or patients with non-lupus
nephropathies. In contrast, COX-2 staining was definitely stronger in specimens
from patients with active LN than control specimens. In active LN, COX-2-specific
staining was localized mainly in the glomeruli, with a weaker signal on tubuli
and in the interstitium. Double-staining studies with an antibody against the
macrophage marker CD68 and an anti-COX-2 antibody definitely showed that COX-2
and CD68 often colocalized on the same cell, with only occasional glomerular COX
2-stained mesangial areas. Patients with non-lupus nephropathies had no increase
in renal COX-2 expression. These results indicate that COX-2 upregulation is a
specific finding of active LN and that monocytes infiltrating the glomeruli
contribute to the exaggerated local synthesis of TXA2. If this is correct, COX-2
may soon become a target for therapeutic intervention in this disease.
PMID- 9644631
TI - In progressive nephropathies, overload of tubular cells with filtered proteins
translates glomerular permeability dysfunction into cellular signals of
interstitial inflammation.
AB - Progression to end-stage renal failure is the final common pathway of many forms
of glomerular disease, independent of the type of initial insult. Progressive
glomerulopathies have in common persistently high levels of urinary protein
excretion and tubulointerstitial lesions at biopsy. Among the cellular mechanisms
that may determine progression regardless of etiology, the traffic of excess
proteins filtered from glomerulus in renal tubule may have functional importance
by initiating interstitial inflammation in the early phase of parenchymal injury.
This study analyzes the time course and sites of protein accumulation and
interstitial cellular infiltration in two different models of proteinuric
nephropathies. In remnant kidneys after 5/6 renal mass ablation, albumin and IgG
accumulation by proximal tubular cells was visualized in the early stage,
preceding interstitial infiltration of MHC-II-positive cells and macrophages. By
double-staining, infiltrates developed at or near tubules containing
intracellular IgG or luminal casts. This relationship persisted thereafter
despite more irregular distribution of infiltrate. Similar patterns were found in
an immune model (passive Heymann nephritis), indicating that the interstitial
inflammatory reaction develops at the sites of protein overload, regardless of
the type of glomerular injury. Osteopontin was detectable in cells of proximal
tubules congested with protein in both models at sites of interstitial
infiltration, and by virtue of its chemoattractive action this is likely mediator
of a proximal tubule-dependent inflammatory pathway in response to protein load.
Protein overload of tubules is a key candidate process translating glomerular
protein leakage into cellular signals of interstitial inflammation. Mechanisms
underlying the proinflammatory response of tubular cells to protein challenge in
diseased kidney should be explored, as well as ways of limiting protein
reabsorption/deposition to prevent consequent inflammation and progressive
disease.
PMID- 9644632
TI - Mineralized bone loss at different sites in dialysis patients: implications for
prevention.
AB - To characterize the magnitude and location of mineralized bone loss, 40 patients
(20 men, 20 women, 29 white, 11 black) with clinically significant renal
osteodystrophy who could be unambiguously classified based on histologic criteria
as having osteitis fibrosa (OF; 20 cases) or osteomalacia (OM; 20 cases) were
studied; they had been on maintenance hemodialysis for 4.6 +/- 3.0 yr. One
hundred forty-two healthy women of similar age and ethnic composition served as
control subjects. In all subjects, the proportions of mineralized bone, osteoid,
and porosity (nonbone soft tissue) were measured separately in cortical and
cancellous bone tissue, from intact full-thickness biopsies of the ilium,
representative of the axial skeleton. The results were related to the volumes of
cortical and cancellous bone tissue separately and to the volume of the entire
biopsy core. Approximately three-quarters of the patients had measurements in the
appendicular skeleton by single photon absorptiometry of the radius and
morphometry of the metacarpal. Disease effects did not differ significantly
between ethnic groups. Mineralized cortical bone volume (per unit of core volume)
was reduced by approximately 45% in both patient groups. Mineralized cancellous
bone volume was significantly increased by 36% in the patients with OF and
nonsignificantly reduced by 9% in the patients with OM; however, the reduction in
the latter patients was significant in relation to tissue volume. The combined
total deficit for both types of iliac bone was approximately 20% in the patients
with OF and approximately 40% in the patients with OM. Significant reductions in
appendicular cortical bone were demonstrated in both patient groups at both
measurement sites. Regardless of the current histologic classification, the major
structural abnormality in the skeleton is generalized thinning of cortical bone
due to increased net endocortical resorption, the most characteristic effect on
bone of hyperparathyroidism. Protection of the skeleton from the adverse
consequences of renal failure will require therapeutic intervention in patients
with no symptoms of either renal or bone disease.
PMID- 9644633
TI - Involvement of R-cadherin in the early stage of glomerulogenesis.
AB - The earliest commitment to the formation of glomeruli is recognizable in S-shaped
bodies. Although cell-cell adhesion seems likely to play a crucial role in this
process, how glomerular epithelial cells segregate from the other parts of the
nephron is unknown. In this study, immunofluorescence microscopy and monoclonal
antibodies specific for mouse R-, E-, P- and N-cadherins were used to examine
which of these adhesion molecules are involved in glomerulogenesis of the mouse
kidney. Weak R-cadherin staining was first found in the vesicle stage, becoming
restricted to glomerular visceral epithelial cells (VEC) during the S-shaped body
stage. The intensity of this staining became stronger in the capillary loop
stage, whereas parietal epithelial cells (PEC) and tubular cells did not stain.
In the maturing stage, VEC gradually lost their staining for R-cadherin. E
cadherin was detected in ureteric buds and the upper limb of S-shaped bodies.
From the capillary loop to the maturing stage, anti-E-cadherin stained epithelial
cells in all tubule segments, but no label was seen in VEC or PEC. P-cadherin was
also stained in the ureteric buds and in the upper limb of S-shaped bodies. N
Cadherin was weakly stained in cells at the vesicle stage, but thereafter
staining of N-cadherin was not detected at any stage of glomerular formation.
Immunoelectron microscopy of differentiating VEC was performed using antibodies
specific to alpha-catenin, which is associated with cadherin. Subsequently,
immunogold particles identifying alpha-catenin were localized on junctions
between primary processes of VEC. These findings indicate that R-cadherin is
uniquely expressed in differentiating VEC, suggesting an important role in the
early stages of glomerulogenesis.
PMID- 9644634
TI - Potassium citrate/citric acid intake improves renal function in rats with
polycystic kidney disease.
AB - Polycystic kidney disease (PKD) has been shown to be exacerbated by acidosis or a
low potassium intake, and there is evidence that administration of alkali might
have a beneficial effect. This study determined whether ingestion of potassium
citrate and citric acid would ameliorate PKD. Healthy normal and heterozygous
littermate Han:SPRD rats with autosomal dominant PKD were provided with either
tap water or 55 mM K3citrate/67 mM citric acid solution (KCitr) to drink starting
at the age of 1 mo. Renal clearance measurements and histologic assessments were
performed when the rats were 3 mo old. KCitr intake did not affect body weight or
urine flow, but completely prevented the decline in GFR found in untreated rats
with PKD. In rats that drank tap water, left kidney GFR averaged (in
microliter/min per 100 g body wt) 503 +/- 78 (n = 9) in normal animals and 242 +/
56 (n = 6) in rats with PKD. In rats that drank KCitr, GFR averaged 562 +/- 123
(n = 7) in normal animals and 534 +/- 103 (n = 7) in rats with PKD. Kidneys of
rats with PKD were approximately double normal size. KCitr treatment did not
affect kidney size, but led to fewer interstitial abnormalities and smaller cysts
in cystic kidneys. KCitr ingestion led to a significantly lower (P < 0.001)
plasma [K+] in rats with PKD (3.3 +/- 0.2 versus 4.1 +/- 0.2 mEq/L in rats on tap
water). Chronic KCitr intake in the young heterozygous Han:SPRD rat with PKD
yields a modest improvement of kidney histology and a dramatic improvement in
GFR. The mechanism of action of KCitr and the long-term effects of this treatment
on renal structure and function in PKD deserve further study.
PMID- 9644635
TI - Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as
inhibitors of Ca2+ ATPase in end-stage renal failure.
AB - The activity of the plasma membrane Ca2+ ATPase of chronic renal failure patients
is decreased by circulating inhibitors yet to be characterized. In this study,
inhibitors of Ca2+ ATPase were isolated from ultrafiltrate of patients with end
stage renal failure. They were identified as dimethylguanosine, phenylethylamine,
and phenylacetic acid by chromatography and mass spectrometry. Ca2+ ATPase
activity was measured spectrophotometrically as the difference in hydrolysis of
ATP in the presence and absence of Ca2+ with different concentrations of ATP and
the isolated substances. All of the identified compounds are sufficiently
lipophilic to penetrate the blood-brain barrier and to accumulate in cerebral
tissue. The inhibitory effects of these agents were additive. The apparent K(m)
values for ATP and Ca2+ were not altered by these substances, suggesting a
noncompetitive mechanism of inhibition. In plasma of healthy subjects, the
substances were not detectable. The Ca2+ ATPase inhibitors identified may play a
role in the pathophysiology of end-stage renal failure and, potentially, in
monitoring toxic effects on cellular Ca2+ metabolism in renal failure.
PMID- 9644636
TI - Outcome of renal replacement therapy in antineutrophil cytoplasmic antibody
associated systemic vasculitis.
AB - Antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV)
frequently leads to end-stage renal disease (ESRD). Potentially fatal disease
activity can continue after the onset of ESRD in both dialysis and transplant
patients, despite the immunosuppressive effects of uremia and rejection
prophylaxis, leading to concerns that such patients have greater morbidity and
mortality. To assess the outcome of AASV patients receiving renal replacement
therapy, a retrospective analysis of 59 patients from our unit who received
chronic dialysis, renal transplantation, or both, was performed. The survival of
AASV patients with ESRD was comparable to national registry controls, as were
both graft and patient survival after renal transplantation. Ther is no evidence
that standard immunosuppressive protocols should be altered for AASV patients
receiving renal transplants. The rate of relapse of vasculitis for patients on
chronic dialysis and after transplantation was 0.09 and 0.02 per patient per
year, respectively. These rates are lower than those of other series and support
the contention that continued immunosuppression after ESRD, as practiced in our
unit, is warranted. Relapses usually responded to cyclophosphamide and high-dose
prednisolone treatment. Significantly, vasculitic flare-ups in dialysis patients
were sometimes initially misdiagnosed as dialysis complications, leading to fatal
delays in effective treatment. Follow-up by physicians experienced in the
diagnosis and treatment of vasculitis activity should continue in these patients.
PMID- 9644637
TI - Dipyridamole decreases renal phosphate leak and augments serum phosphorus in
patients with low renal phosphate threshold.
AB - It has been shown that an acute infusion of dipyridamole increased renal
phosphate reabsorption in rats and humans. A prospective study was performed to
determine whether chronic treatment by dipyridamole given orally could decrease
renal phosphate leak and increase serum phosphorus in patients with idiopathic
low renal phosphate threshold (TmPO4/GFR < 0.77 mM). Sixty-four patients with low
TmPO4/GFR were included and treated with dipyridamole (75 mg, 4 times daily) for
more than 12 mo. Serum phosphorus, TmPO4/GFR, parathyroid hormone, serum calcium,
and 1,25-dihydroxyvitamin D were measured sequentially before treatment, and
after 3, 6 to 9, and 12 mo of treatment. Under chronic treatment with
dipyridamole, TmPO4/GFR and serum phosphorus significantly increased in 80% of
patients within 3 mo, with maximal values reached within 9 mo. This improvement
persisted after 12 mo of treatment. In 28 patients, 1,25-dihydroxyvitamin D
concentrations were above the normal range (> 42 pg/ml) and normalized in
parallel with the increase of serum phosphorus. The 24-h calcium excretion (which
was initially increased in patients with high vitamin D concentrations) and
urolithiasis decreased under treatment. Ionized serum calcium and parathyroid
hormone remained unchanged. After 2 yr, treatment was discontinued in three
patients; serum phosphorus and TmPO4/GFR decreased within 1 mo after
discontinuation. Dipyridamole at a dose of 75 mg 4 times daily increases low
TmPO4/GFR and improves hypophosphatemia in patients with renal phosphate losses
and can be used to treat these patients.
PMID- 9644638
TI - Familial aggregation of renal disease in a population-based case-control study.
AB - Family history of renal disease has been associated with an increased risk of end
stage renal disease (ESRD). It is uncertain whether this risk is mediated by
familial aggregation of risk factors for ESRD, such as diabetes and hypertension.
The association of ESRD with familial aggregation of renal disease was examined
in a large, population-based case-control study conducted in Maryland, Virginia,
West Virginia, and Washington, DC. The number of first-degree relatives who were
affected with any type of renal disease was compared between 689 newly treated
ESRD patients registered in the Medicare ESRD program (92% of all eligible
incident cases presenting between January and July of 1991) and 361 control
subjects without ESRD who were selected by random-digit dialing (90% response
rate). Patients and control subjects were frequency matched by age; patients with
ESRD caused by polycystic kidney disease and other known hereditary kidney
diseases were excluded. Analysis was conducted using multiple logistic
regression. After controlling for the proband's age, gender, race, family size,
socioeconomic status, and personal and family histories of diabetes and
hypertension, having one first-degree relative with renal disease increased the
odds of ESRD by 1.3 (95% confidence interval, 0.7 to 2.6) and having two or more
affected first-degree relatives increased the odds of ESRD by 10.4 (95%
confidence interval, 2.7 to 40.2). These data support familial aggregation of
renal disease in excess of that predicted by clustering of diabetes and
hypertension within families, suggesting that either genetic susceptibility or
environmental exposures shared within families increase the risk of developing
ESRD. This risk is also much higher when two or more first-degree relatives have
renal disease. Unraveling the molecular basis of this increase in risk may
provide new avenues for treatment and prevention of ESRD.
PMID- 9644639
TI - Intermediate-density lipoprotein as an independent risk factor for aortic
atherosclerosis in hemodialysis patients.
AB - Patients with chronic renal failure often show accumulation of intermediate
density lipoprotein (IDL). Because recent studies have emphasized the
atherogenicity of IDL in the general population, we evaluated the relationship
between this lipoprotein and aortic atherosclerosis in uremic patients treated
with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive
index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and
gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by
ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL.
Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay.
Aortic PWV was significantly higher in the hemodialysis patients than in the
control subjects. The hemodialysis group showed a significant increase in VLDL
and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the
control levels. Lp(a) levels did not differ between the two groups. In the
hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively
with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not.
Multiple regression analyses indicated that plasma triglycerides, independent of
HDL cholesterol, had a significant association with aortic PWV in the
hemodialysis patients but not in the control subjects. Further analyses revealed
that aortic PWV in the hemodialysis patients had a significant and independent
association with IDL cholesterol, whereas aortic PWV in the control subjects had
significant and independent associations with HDL cholesterol and Lp(a). These
results demonstrate that IDL is the lipoprotein fraction most closely associated
with aortic PWV in the hemodialysis patients.
PMID- 9644640
TI - Increased peritoneal membrane transport is associated with decreased patient and
technique survival for continuous peritoneal dialysis patients. The Canada-USA
(CANUSA) Peritoneal Dialysis Study Group.
AB - The objective of this study was to evaluate the association of peritoneal
membrane transport with technique and patient survival. In the Canada-USA
prospective cohort study of adequacy of continuous ambulatory peritoneal dialysis
(CAPD), a peritoneal equilibrium test (PET) was performed approximately 1 mo
after initiation of dialysis; patients were defined as high (H), high average
(HA), low average (LA), and low (L) transporters. The Cox proportional hazards
method evaluated the association of technique and patient survival with
independent variables (demographic and clinical variables, nutrition, adequacy,
and transport status). Among 606 patients evaluated by PET, there were 41 L, 192
LA, 280 HA, and 93 H. The 2-yr technique survival probabilities were 94, 76, 72,
and 68% for L, LA, HA, and H, respectively (P = 0.04). The 2-yr patient survival
probabilities were 91, 80, 72, and 71% for L, LA, HA, and H, respectively (P =
0.11). The 2-yr probabilities of both patient and technique survival were 86, 61,
52, and 48% for L, LA, HA, and H, respectively (P = 0.006). The relative risk of
either technique failure or death, compared to L, was 2.54 for LA, 3.39 for HA,
and 4.00 for H. The mean drain volumes (liters) in the PET were 2.53, 2.45, 2.33,
and 2.16 for L, LA, HA, and H, respectively (P < 0.001). After 1 mo CAPD
treatment, the mean 24-h drain volumes (liters) were 9.38, 8.93, 8.59, and 8.22
for L, LA, HA, and H, respectively (P < 0.001); the mean 24-h peritoneal albumin
losses (g) were 3.1, 3.9, 4.3, and 5.6 for L, LA, HA, and H, respectively (P <
0.001). The mean serum albumin values (g/L) were 37.8, 36.2, 33.8, and 32.8 for
L, LA, HA, and H, respectively (P < 0.001). Among CAPD patients, higher
peritoneal transport is associated with increased risk of either technique
failure or death. The decreased drain volume, increased albumin loss, and
decreased serum albumin concentration suggest volume overload and malnutrition as
mechanisms. Use of nocturnal cycling peritoneal dialysis should be considered in
H and HA transporters.
PMID- 9644641
TI - Neoral conversion from Sandimmune in maintenance renal transplant patients: an
individualized approach.
AB - When converting maintenance renal allograft recipients from Sandimmune
(cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion
ratio of 1:1 may not be optimal, in part because of the variability in absorption
of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio,
an individualized approach to the management of dosing was applied. In this
article, close monitoring, which began at the time of conversion, and rapid
response to potentially meaningful changes in cyclosporine trough levels early in
the postconversion course were used to maintain patients' cyclosporine troughs at
preconversion levels. The results of cyclosporine dose changes after converting
stable, maintenance renal transplant patients from CsA (once daily and twice
daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most
patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough
levels, and 64% of the patients attained their CsA-ME maintenance dose by study
week 4. Logistic regression analysis identified one significant predictor
concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0
mg/kg per d were more likely to require dose reduction (P < 0.0001). Although
firm guidelines for dose modification after conversion from CsA to CsA-ME cannot
be provided because of the individual nature of cyclosporine absorption, an
individualized approach to patient management is recommended. Patients with
higher CsA doses before conversion are particularly likely to require dose
reduction early in the postconversion course. With CsA-ME, good absorbers of
cyclosporine remain good absorbers, or become better absorbers, whereas poor
absorbers become good absorbers.
PMID- 9644642
TI - The prognostic significance of specific arterial lesions in acute renal allograft
rejection.
AB - Diagnosis of allograft dysfunction relies on the assessment of arterial lesions.
This study was designed to evaluate the prognostic significance of common
specific vascular lesions in acute allograft rejection. Renal allograft biopsies
(n = 111) with acute cellular rejection were scored for endarteritis, mononuclear
cell adherence to endothelial cells, endothelial activation, fibrinoid necrosis,
foam cells, and intimal fibrosis. These vascular lesions and other classic
histologic features were correlated with outcome. Rejection with endarteritis
(found in 54% of biopsies) was less responsive to steroid treatment than
rejection without endarteritis, as judged by recovery of creatinine in 3 wk (P =
0.03). Larger numbers of sampled arteries improved the predictive accuracy.
Sticking of mononuclear cells to endothelial cells also correlated with steroid
resistance (P < 0.05). Rejection with or without endarteritis responded to
OKT3/antithymocyte globulin treatment equally well (61% versus 65%,
respectively). Rejection with fibrinoid arterial necrosis (4% of biopsies) did
not respond to either steroids or antibodies (0%). One-year graft failure was 21%
without endarteritis, 28% with endarteritis, and 100% with fibrinoid necrosis.
Activated endothelial cells and interstitial hemorrhage were associated with
endarteritis and graft failure (all P < 0.05). None of the other scored features
had any statistically significant correlation with outcome. Thus, specific
arterial lesions (endarteritis, fibrinoid necrosis, activated endothelial cells,
mononuclear cell margination) and interstitial hemorrhage, but not the extent of
the interstitial infiltrate or tubulitis, are correlated with response to
antirejection therapy and/or 1-yr clinical outcome. Grading systems for
therapeutic trials and clinical management should emphasize scoring of specific
vascular lesions.
PMID- 9644643
TI - High rate of acute rejections in renal allograft recipients with thrombophilic
risk factors.
AB - Inherited and acquired thrombophilic disorders predispose patients for
thromboembolic and probably other occlusive vascular events that occur when
additional risk factors play in concert. Because acute rejections in renal
transplant recipients may reflect vascular events, and an impairment of the
fibrinolytic system in immunosuppressed patients has been previously described,
the implications of genetic or acquired risk factors of thrombophilia for the
occurrence of early acute rejections after kidney transplantation were evaluated.
The following risk factors of thrombophilia were determined in 97 patients after
cadaveric kidney transplantation: factor V Leiden mutation, protein S, protein C,
and antithrombin deficiency. In a retrospective analysis, the prevalence of acute
rejections, the histologic classification when rejection episodes had been
confirmed by biopsy, and other vascular complications were evaluated. In 21 of
the 97 patients, an inherited or acquired risk factor of thrombophilia was
detected. Prevalence of acute rejections was 71% in the first 6 mo after
transplantation in patients with a thrombophilic disorder and significantly
higher compared with patients without thrombophilia (41%; P = 0.017). The
distribution of classic risk factors associated with acute rejections, such as
number of human leukocyte antigen mismatches or percentage of panel-reactive
antibodies, was similar in patients with and without thrombophilia. In the eight
patients with thrombophilia and histologically proven acute rejection, four
patients had an acute vascular rejection, and in two patients a vascular
involvement was suspected. Furthermore, prevalence of cerebral or coronary
vascular disease, or venous thromboembolic complications, was significantly
higher in patients with a thrombophilic clotting defect (67%) compared with
patients with normal hemostasis parameters (28%; P < 0.002). It is concluded that
renal allograft recipients with thrombophilia are at risk of developing an acute
rejection or other vascular event. Although the determination of thrombotic risk
factors was performed at least 3 mo after an acute rejection episode, it can be
presumed that acute rejection episodes are associated with subsequent coagulatory
abnormalities with further consequences for transplant survival. Thus,
pretransplant evaluation of genetic and acquired risk factors of thrombophilia is
recommended.
PMID- 9644644
TI - Silent infection in clotted hemodialysis access grafts.
AB - Thrombotic and infectious complications are frequent causes of hemodialysis
vascular access failure and contribute considerably to the cost of care for
chronic hemodialysis patients. Although there is clear indication for removal of
patent grafts in unresolved bacteremia, there are no guidelines for the
management of clotted nonfunctioning grafts. To evaluate for the existence and
clinical relevance of silent infection in clotted nonfunctioning hemodialysis
grafts, a study was conducted with a series of 20 hemodialysis patients who
presented with fever (15 patients), or fever and clinical signs of sepsis (five
patients), in whom the source of infection was not immediately localized to any
organ system. Comparison was made with 21 asymptomatic patients with clotted
grafts who served as control subjects. All patients and control subjects came
from a pool of 115 chronic hemodialysis patients in an outpatient hemodialysis
unit in the Houston metropolitan area, who were on hemodialysis for a period of
time ranging from 3 to 15 yr. Indium scans were performed, followed by removal of
the clotted grafts in all patients and control subjects. Bacterial cultures of
the recovered surgical material and blood were done concomitantly in all study
participants. Indium scans showed positive uptake in or around the clotted grafts
in all of the patients and in 15 of the control subjects. Purulent material was
found in the grafts in all patients and in 13 of 15 indium scan-positive control
subjects. When positive, blood culture pathogens were identical to those cultured
from the graft material in all instances. The predominant pathogens were
Staphylococcus aureus, followed by Staphylococcus epidermidis. There was no
evidence of graft infection in the control subjects if indium scan was negative.
Chart review dating back to the start of dialysis revealed five past infectious
episodes in the patient group, compared with four in the control group. These
findings suggest that clotted nonfunctioning grafts are frequent harbingers of
infection. They should be suspected as the source of infection in every
hemodialysis patient that presents with fever, even in the absence of clinical
signs of graft site infection.
PMID- 9644645
TI - Beta-adrenoceptor-stimulated renin release is blunted in old rats.
AB - Plasma renin activity (PRA) was similar in young versus old male Sprague Dawley
rats under unstressed conditions (1.3 +/- 0.2 versus 1.8 +/- 0.3 ng angiotensin
I/ml per min). Airjet stress increases PRA in young but not old rats (13.9 +/-
3.8 versus 2.9 +/- 0.8 ng angiotensin I/ml per min), respectively. This response
is ablated in young rats by beta-adrenoceptor blockade, suggesting that the
increased PRA is mediated by beta-adrenoceptors, and this response was blunted in
old rats.
PMID- 9644646
TI - Protecting single-kidney allografts from long-term functional deterioration.
PMID- 9644647
TI - Primary focal segmental glomerulosclerosis.
PMID- 9644648
TI - Renal tubular secretion of potassium in the normal dog.
PMID- 9644649
TI - Statistical science and quantitative understanding.
AB - Authors of papers in biological journals need to make their uses of statistical
methods and software explicit and maximally comprehensible. Editors and referees
have important responsibilities for this. Inexact use of technical terminology
causes confusion. Computer software is invaluable but not infallible. Graphical
presentation should not conceal numerical results. Tests of statistical
significance should be reserved for specific needs, which will rarely include
multiple comparison procedures. Experiments that involve repeated measurements
need special care in statistical analysis. Full attention should be given to
principles of statistical estimation as well as to choice of appropriate
statistical technique. At all times, ethical standards of scientific integrity
must contribute to precision and clarity. Clinical research that neglects well
established statistical principles may be intrinsically unethical.
PMID- 9644650
TI - Comparison of sex differences in guinea-pig maximization test for detection of
skin-sensitizing potential using OECD recommended positive control sensitizers.
AB - Both male and female guinea pigs are widely used in tests to detect the skin
sensitizing potential of new chemicals. The aim of the present study was to
investigate the influence of the animal gender on sensitization rates, with the
guinea-pig maximization test (GPMT) using OECD recommended positive control
sensitizers, and the differences of the density of Langerhans cells in male and
female guinea pigs. The sensitization rates of males and females challenged with
HCA, MBT or benzocaine gave almost the same results. There were no statistical
differences between the mean responses of males and females. These results were
confirmed by rechallenge with the OECD recommended positive controls.
Furthermore, the density of Langerhans cells in abdominal epidermis in males
(1229 +/- 45 cells/mm2) was the same as that in females (1242 +/- 89 cells/mm2).
These results indicate that there is no significant influence of guinea-pig
gender in the assessment of skin-sensitizing potential using the GPMT.
PMID- 9644651
TI - Formation of 8-oxodeoxyguanosine in liver DNA and hepatic injury by peroxisome
proliferator clofibrate and perfluorodecanoic acid in rats.
AB - In this study, we examined whether the production of hydrogen peroxide by
peroxisome proliferators causes oxidative DNA damage in the form of 8
oxodeoxyguanosine (8-oxodG) and hepatic injury, and whether it is related to
their tumor-promoting or carcinogenic activities in female rats treated with the
peroxisome proliferators clofibrate and perfluorodecanoic acid (PFDA). Clofibrate
has tumor-promoting and carcinogenic activities, whereas PFDA does not. We also
tested whether peroxisome proliferators directly induce mutagenic events in
Salmonella typhimurium strains TA 98 and TA 1537. Rats were treated either by 5%
clofibrate in diet or by an i.p. injection of corn oil containing 10 mg/kg body
weight of PFDA every week for 2 or 8 weeks. 8-OxodG in liver DNA was analyzed by
HPLC coupled with an electrochemical detector. Hepatic injury was evidenced by
liver enlargement and by levels of serum enzymes, aspartate aminotransferase
(AST) and alanine aminotransferase (ALT), and hepatic gamma-glutamylpeptidase
(gamma-GT) activity. Clofibrate and PFDA increased the activity of catalase about
or less than 2-fold, whereas FAO activity was increased about 6 to 7-fold by
clofibrate and about 3 to 4-fold by PFDA. Neither clofibrate nor PFDA induced
mutation at any dose tested. Clofibrate significantly increased the formation of
8-oxodG, but PFDA only slightly increased. Serum AST and ALT levels, and hepatic
gamma-GT activity were not significantly changed at both time points, whereas the
ratio of liver/body weight was significantly increased by clofibrate and PFDA at
8 weeks. These data imply that the magnitude of the production of hydrogen
peroxide-generated FAO is related to the induction of oxidative DNA damage by
peroxisome proliferators, and their tumor-promoting or carcinogenic activities.
However, the effect of hydrogen peroxide in hepatic injury is not clear.
PMID- 9644652
TI - Involvement of vitamin D in lead-induced cutaneous calcification in rodents.
AB - Experimental cutaneous calcification was induced by a subcutaneous injection of
lead acetate in parathyroidectomized (PTX) rats and vitamin D-deficient rats
whose plasma calcium concentrations were controlled by diets containing various
amounts of calcium. Although, in PTX rats, the calcium content of the calcified
plaque induced by lead acetate was correlated with their plasma calcium
concentration, calcium content of the calcified plaque in vitamin D-deficient
rats with normocalcemia was significantly lower than those in control and PTX
rats with normocalcemia. A subcutaneous administration of 1 alpha,25
dihydroxyvitamin D3 (1 alpha,25(OH)2D3) following the lead acetate injection
increased calcium content of the calcified plaque in vitamin D-deficient mice,
suggesting the involvement of vitamin D in the cutaneous calcification. As the
synthesis of osteocalcin, osteopontin and interleukin-1 (IL-1) receptor is well
known to be increased by 1 alpha,25(OH)2D3, gene expressions of mRNAs of these
proteins were examined in the skin with calcified plaque by reverse transcription
polymerase chain reaction (RT-PCR) analysis. These mRNA expressions in the skin
with calcified plaque were increased by a subcutaneous administration of 1
alpha,25(OH)2D3 following the lead acetate injection. On the contrary, they
decreased in vitamin D-deficient mice. These findings suggest that vitamin D is
directly involved in the process of experimental calcification.
PMID- 9644653
TI - Effect of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene on liver injury induced by
repeated exposure to galactosamine plus carbon tetrachloride in rats.
AB - The protective effects of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A),4-phenyl
1,3-dithia-2-thioxo-cyclopent- 4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2
thioxo-cyclopent-4-ene (DT827C) on liver injury induced by D-galactosamine plus
carbon tetrachloride (D-GalN + CCl4) and that of DT827B on liver injury induced
by thioacetamide were studied using male rats. Out of the three DT827 series of
compounds, DT827B was more effective on liver injury induced by the combination
exposure to D-GalN + CCl4 for 4 weeks, and accordingly the following two
experiments were carried out using DT827B only. Twelve-week administration of
DT827B at dose levels of 5, 10 and 20 mg/kg/day revealed a therapeutic effect
against liver injury induced by D-GalN + CCl4 dose-dependently, and another
twelve-week administration of DT827B at the same three dose levels also revealed
a therapeutic effect against liver injury induced by thioacetamide dose
dependently. A hepatoprotective potential of DT827B was suggested under the
conditions of these studies.
PMID- 9644654
TI - Prolongation of PT and APTT under excessive anticoagulant in plasma from rats and
dogs.
AB - Prothrombin time (PT) and activated partial thromboplastin time (APTT) were
studied under excessive sodium citrate using the plasma from rats and beagle
dogs. Addition of sodium citrate into the plasma caused a prolongation of PT and
APTT. The prolongation was dependent on the concentration of sodium citrate or
calculated hematocrit. The degree of prolongation was more severe in rats than in
dogs, and in APTT than in PT. These results suggest that an artificial
prolongation of PT and APTT occurs under excessive sodium citrate (e.g., elevated
hematocrit), and that the degree differs between species and between parameters.
PMID- 9644655
TI - [New role of stress protein heme oxygenase--its relationship with
physiopathology].
PMID- 9644656
TI - [Application of new technology to toxicology: dynamic analysis of hematopoietic
stem cells-BUUV method].
PMID- 9644657
TI - [Risk evaluation of neurotoxicity].
PMID- 9644658
TI - [Endocrine disrupters and toxicology--tests for detection and evaluation of
endocrine disrutptive actions].
PMID- 9644659
TI - [International coordination of guidelines for genetic toxicity tests-- trends in
ICH and OECD (second report)].
PMID- 9644661
TI - [Angle heterophoria: fiction or reality].
PMID- 9644660
TI - [Everything depends on gold].
PMID- 9644663
TI - [Determining visual acuity using European normal values: scientific principles
and possibilities for automatic measurement].
AB - PSYCHOMETRIC FUNCTION: According to the European standard EN ISO 8596 the Landolt
C in 8 different orientations has to be used to measure visual acuity. With
decreasing size of the Landolt-C the hit rate declines from 100% to the chance
level of 12.5%. This gradual transition is described by the "psychometric
function". The steepest point of the psychometric function is in the middle
between 100 and 12.5, i.e., at 56.25%. This point of the psychometric function
(approximated by 5 of 8 Landolt-Cs) has been selected as the threshold for visual
acuity, because it is there that the visual acuity is influenced least by
(incidental) fluctuations. The subject has to answer by forced choice; a response
like "I cannot detect anything" is not acceptable. "NORMAL" VISUAL ACUITY: Cannot
be assigned to a certain value, like 1.0 or 6/6. With the standard test
procedure, visually healthy, young subjects achieve a visual acuity of about 2.0
or 12/6, while in senior subjects 0.5 (3/6) may be "normal". AVERAGING VISUAL
ACUITY: Logarithmic, not arithmetic, scaling of visual acuity approximates the
perceptual metric. Consequently, visual acuity values may not be averaged
arithmetically. Instead, three steps are required: all values have to be
converted to logarithms, then averaged, and finally the average can be
reconverted. Geometric averaging is equivalent. "MINIMUM ANGLE OF RESOLUTION" NOT
NECESSARY: MAR is the reciprocal of visual acuity. In many studies, clinical
outcome has been assessed using log(MAR). Though statistically correct, this term
is unnecessary, as log(acuity) has identical statistical properties. Furthermore,
log(MAR) is contra-intuitive as its value becomes smaller when vision improves.
COMPUTER-ASSISTED INSTRUMENTATION: Facilitates complying with the EN ISO 8596.
For instance, the Freiburg Visual Acuity Test relieves the examiner from
observing whether 5 responses have been correct, and that not more than 8 tests
are given per level.
PMID- 9644664
TI - [Objective assessment of minimum visual acuity by suppression of optokinetic
nystagmus].
AB - PURPOSE: To develop and to validate an objective method which allows an
estimation of the visual acuity (VA) of adults. METHODS: A horizontal optokinetic
nystagmus (OKN) was elicited by a vertical rectangular grating presented on a PC
screen and was recorded by an infrared reflection method. Superimposition of
three stationary black detection stimuli was used to suppress the OKN. The size
of these stimuli was increased every two seconds, in ten steps. Suppression of
the OKN was taken as an indication that the stimuli were detected. The relation
between the smallest effective stimulus and logVA was evaluated in 65 healthy
volunteers (130 eyes) with artificially reduced VA and 425 cooperative patients
(842 eyes) whose VA was reduced due to different etiologies. The tolerance
intervals of logVA related to the discrete detection stimuli were calculated.
RESULTS: The method allows an estimation of the least expectable VA in steps of
0.8, 0.32, 0.25, 0.12, 0.1, 0.06, 0.03 und 0.025 due to the smallest value of
three trials. The least VA of strabismic amblyopic eyes can only be estimated in
steps of 0.16, 0.06, and 0.02. A VA > 0.02 can be proven with high reliability.
CONCLUSION: The method allows a clinically useful, objective estimation of the
least VA without observer bias in non-amblyopic eyes.
PMID- 9644665
TI - [Improved fixation of unilateral suture operation of the rectus medialis muscle
of the amblyopic eye].
AB - BACKGROUND: Strabismus surgery influences the retinal fixation positively, as
described by Bohme, Ehrich and Cuppers. Fadenoperation (Posterior Fixation) of
the medial rectus muscle allows a more specific approach. It reduces the
influence of overadduction and latent-type nystagmus on the retinal fixation,
which becomes more central and more controlled after such an operation. PATIENTS:
This effect is very marked in infants up to 2 years of age, but still significant
in older children with intolerance for occlusion, and motility-dependent
excentric fixation. About half of the 70 cases observed reached a useful fixation
and acuity by "surgical pleoptics". With respect to the otherwise poor prognosis
of these cases, this result can be regarded as favourable.
PMID- 9644666
TI - [Changes in subjective cyclodeviation and objective cycloposition after modified
Harada-Ito operation in acquired trochlear paralysis].
AB - BACKGROUND: After recently published own investigations on subjective and
objective cyclorotatory changes following inferior oblique recession for inferior
oblique overaction, it was our aim to determine and to compare subjective and
objective cyclorotatory changes following a modified Harada-Ito procedure for
acquired trochlear palsy. PATIENTS AND METHODS: Eight patients suffering from
acquired uni-(n = 3) or bilateral (n = 5) trochlear palsy were investigated
before surgery and 1 day, 3 days and 4 months after surgery. Subjective
cyclodeviation was assessed by Harms' tangent scale. Objective cycloposition was
measured by means of fundus cyclometry using an infrared Scanning Laser
Ophthalmoscope. RESULTS: The immediate postoperative incyclorotatory effect was
12 degrees in the unilateral group and 18 degrees in the bilateral group.
Subjective and objective changes were nearly equal in both groups, with a
subjective over-effect of 1 degree. After two days of binocular stimulation a
marked regression of the surgical effect was found which still increased after
four months. The long term incyclorotatory effect was subjectively and
objectively nearly equal in the unilateral group which showed a relaps of
subjective excyclodeviation of 5 degrees: in the bilateral group, the subjective
effect was more pronounced than the objective effect, the immediate postoperative
over-effect being disappeared. CONCLUSIONS: In contrast to our results concerning
inferior oblique muscle recession for strabismus sursoadductorius, subjective and
objective cyclorotatory changes did not differ grossly following a modified
Harada-Ito procedure. Subjective and objective short and long term regression was
confirmed which objectively exceeded the amount of over-correction. As the
underlying cause mechanical and sensory mechanisms are discussed.
PMID- 9644667
TI - [Orthoptic problems after macular rotation with and without muscle surgery].
AB - BACKGROUND: In spite of new therapeutic approaches the treatment of age related
macular degeneration remains unsatisfying. Macular rotation is so far only a
rarely employed surgical procedure, where the macula is translocated to an area
with intact retinal pigment epithelium. The aim of this study was to elucidate
the orthoptic problems of macular rotation and describe possible treatment
modalities. PATIENTS AND METHOD: Between February and July of 1997 a macular
rotation was performed in 8 patients with exsudative macular degeneration,
followed by silicone oil removal and implantation of an intraocular lens. In 3
out of 8 patients the oblique muscles were transposed at the beginning of the
surgery to produce an excylotropia. In all patients visual acuity for distance
and near was determined pre- and postoperatively along with a complete orthoptic
status including measuring of cyclotropia. Mean postoperative follow-up was 5.5
months. RESULTS: Due to the unilateral ectopia of the macula all patients
presented with a postoperative strabismus with vertical deviation of 2 degrees to
10 degrees. The change of the visual axis resulted in a displacement of the
pupillary reflex. The patients described a cyclotropia of 12 degrees to 45
degrees corresponding to the ophthalmoscopically estimated angle of retinal
rotation. Patients after surgery of the oblique muscles showed less cyclotropia
with an angle of 12 degrees to 20 degrees. They were less disturbed by diplopia
and tilted visual impression than those without muscle surgery. All patients
exhibited an abnormal head position with chin up and tilt to the side of the
operated eye. CONCLUSION: Macular rotation always causes diplopia because of the
unilateral ectopia with cyclotropia and vertical deviation. These problems can be
considerably reduced by combining macular rotation surgery with oblique muscles
surgery. It may well be that in the future these problems can be completely
resolved by additional surgery on the rectus muscles.
PMID- 9644668
TI - [Normal accommodative convergence excess--long-term follow-up of conservative
therapy with bifocal eyeglasses].
AB - BACKGROUND: In patients with normaccommodative convergence excess it is possible
to reduce or eliminate the excess of accommodative convergence by adding plus
lenses. The resulting reduction of near deviation can lead to an improvement in
the quality of binocular vision at near, and also to a better compensation of an
esophoria at near. The aim of the paper was to study long term results in
patients with small angle esotropia and esophoria and accommodative convergence
excess treated by bifocals. METHODS: Clinical data of 91 patients were analysed
retrospectively. Among them were 13 patients with esophoria, 32 patients with
microesotropia and 46 with microesotropia and a phoric component. An orthoptic
status was performed every three months and at every examination it was tried to
reduce the added plus lenses. The mean follow up was 5.6 +/- 2.4 years (range:
1.1-13.2). RESULTS: The mean onset of strabismus was similar in all groups: i.e.
2.5 (+/- 1.7) years. The patients received their first bifocals on average 3.4
(+/- 1.9) years later. In 40 of the 91 patients the near addition could be
stopped because of sufficient decrease of accommodative convergence excess during
the follow-up period. The convergence excess decreased continuously in all
patients with esophoria and microesotropia and the additional plus lenses could
be stopped on average after 6.4 (3.5-8.4) years (esophoria) and 5.0 (2.6-8.1)
years (microesotropia) respectively. In patients with microesotropia and an
additional phoric deviation bifocals were only partly successful to reduce the
convergence excess. The basic angle decompensated in more than half of the
patients (27 out of 46) and was operated in 14 cases by unilateral
resection/recession procedure. After the operation the convergence excess
decreased rapidly and the bifocals could be stopped after 4.4 (3.4-7.4) years. In
the remaining 19 cases it was possible to reduced the convergence excess with
bifocals in 8 patients after about 8.1 (4.1-9.3) years and in some of the
remaining 11 cases a Fadenoperation has been suggested. CONCLUSION: While wearing
bifocals the accommodative convergence excess decreased completely in patients
with esophoria and microesotropia. In the condition with markedly reduced
binocular vision and a large phoric component at far and near, the convergence
excess decreased only in some of the patients while wearing bifocals.
Conventional strabismus surgery to reduce the basic angle has a positive
influence. A Fadenoperation is only necessary in a few cases.
PMID- 9644669
TI - [Fixation disparity with the Pola pointing test: not representative for eye
position under natural viewing conditions].
AB - BACKGROUND: According to certain findings obtained with the Zeiss Polatest, H.J.
Haase defined a "Fixation Disparity Type One". In this diagnosis, the
"Zeigertest" is particularly important. The Zeigertest consists of a central ring
presented to both eyes for fixation, a vertical clock hand presented to the right
eye and two markings at the six and twelve o'clock positions presented to the
left eye. All parts are surrounded by a binocularly visible frame. Subjects with
a "Fixation Disparity Type One" see a misalignment between the clock hand and the
peripheral markings. We investigated (1) whether the perceived misalignment
correlated with an objective deviation of the eyes from orthovergence and (2)
whether subjects with a "Fixation Disparity Type One" had a deviation of the eyes
from orthovergence when looking at a natural, i.e., fully fusionable object.
SUBJECTS AND METHODS: Out of 303 medical students, 10 subjects with a "Fixation
Disparity Type One" were selected and asked to indicate the perceived alignment
or misalignment in the Zeigertest with a laser pointer. Two subjects without
fixation disparity served as controls. The position of both eyes was recorded
using the search coil technique. One of the 10 subjects with "Fixation Disparity
Type One" had to be excluded due to excessive blinking. Experiment 1: In the
beginning all parts of the Zeigertest were presented to both eyes (natural
viewing condition). Then, the object for one of the eyes was switched off leaving
the frame as the only fusional stimulus. The outcome variable was a refixation
movement of the other eye. This experiment is similar to the unilateral cover
test. Experiment 2: In the beginning all parts of the Zeigertest were presented
to both eyes (natural viewing condition). Then, the original Zeigertest was
switched on (clock hand presented only to the right eye, peripheral markings only
to the left eye). The outcome variable was a change of vergence. RESULTS:
Experiment 1: A significant refixation movement did not occur in any of the
subjects. Experiment 2. In all 9 subjects with "Fixation Disparity Type One" the
vergence changed significantly between 2.4 and 14.9 arcmin. The change of
vergence correlated significantly with the angle of the perceived misalignment
between clock hand and peripheral markings. CONCLUSION: A fixation disparity
ascertained at the Zeigertest does not indicate a fixation disparity under
natural viewing conditions.
PMID- 9644670
TI - [Measuring the effect of eyeglasses on determination of squint angle with
Purkinje reflexes and the prism cover test].
AB - BACKGROUND: The alternating prism and cover test is the conventional test for the
measurement of the angle of strabismus. The error induced by the prismatic effect
of glasses is typically about 27-30%/10 D. Alternatively, the angle of strabismus
can be measured with methods based on Purkinje reflex positions. This study
examines the differences between three such options, taking into account the
influence of glasses. MATERIALS AND METHODS: The studied system comprised the
eyes with or without glasses, a fixation object and a device for recording the
eye position: in the case of the alternate prism and cover test, a prism bar was
required; in the case of a Purkinje reflex based device, light sources for
generation of reflexes and a camera for the documentation of the reflex positions
were used. Measurements performed on model eyes and computer ray traces were used
to analyze and compare the options. RESULTS: When a single corneal reflex is
used, the misalignment of the corneal axis can be measured; the error in this
measurement due to the prismatic effect of glasses was 7.6%/10 D, the smallest
found in this study. The individual Hirschberg ratio can be determined by
monocular measurements in three gaze directions. CONCLUSIONS: The angle of
strabismus can be measured with Purkinje reflex based methods if the fundamental
differences between these methods and the alternate prism and cover test, and if
the influence of glasses and other sources of error are accounted for.
PMID- 9644672
TI - [Experiences with hemangiopericytoma in cranial base surgery].
AB - BACKGROUND: Haemangiopericytomas are rare vascular neoplasms which show either
slow local tumour growth or aggressive progression in size with a high tendency
of recurrence and metastasis. Manifestations of haemangiopericytomas in the area
of the nose and sinuses are supposed to have a relatively benign course. To date
clinical and histological parameters for prognosis are uncertain. Therefore in a
quite large number of cases only the clinical course allows to evaluate the
dignity of a haemangiopericytoma. PATIENTS AND RESULTS: We present our experience
with five haemanglopericytomas in contact with the skull base out of a total
number of 457 skull base tumours. The site of origin of these five
haemangiopericytomas were: nasal septum, pterygopalatine fossa, oronasopharynx,
temporal bone, and parotid gland. All neoplasms showed primary or recurrent tumor
in contact with the skull base and an intracranial extension was observed twice.
One patient died postoperatively of a cerebral infarction. Three patients showed
one or more recurrences which were treated surgically. In one case 5 recurrences
occurred. Despite of 4 surgical procedures within a period of 15 months, the
tumour could be controlled only for a short period of time, and the patient died
16 months after the first operation. CONCLUSION: One has to consider that
haemangiopericytomas of the head and neck show a potential malignant course. The
vascular tumor may recur decades later. Adequate therapy and life-long follow-up
are therefore mandatory in haemangiopericytomas. Complete surgical resection of
the tumour is usually the treatment of choice, in spite of the high degree of
surgical skill required, especially in advanced tumour and in case of recurrence.
PMID- 9644671
TI - [The Vibrant Soundbridge System: a new kind of hearing aid for sensorineural
hearing loss. 1: Function and initial clinical experiences].
AB - INTRODUCTION: Patients suffering from moderate to severe cochlear hearing
impairment can not be considered for cochlear implantation on account of their
relatively good residual hearing. Conventional hearing aids, on the other hand,
have considerable disadvantages which clearly limit the benefit for these
patients, e.g. feedback, sound distortion, unfavorable conditions for frequency
transfer, occlusion, and recurrent infections of the auditory canal. In addition,
many patients complain about a poor speech intelligibility in noise. VIBRANT
SOUNDBRIDGE HEARING PROSTHESIS: Implantable hearing aids offer a new approach for
improved auditory rehabilitation. The Vibrant Soundbridge system is based on an
electromagnetic system, which is linked directly to the intact ossicular chain.
Due to the high sound quality and the high frequency characteristic this system
is ideally suited for the above-mentioned patient group. The usual disadvantages
of conventional hearing aids can be avoided. Externally visible is merely the
audio processor, which is worn in the retroauricular area and covered by hair.
This processor transfers data and power via magnetic attachment transcutaneously.
PATIENT POOL: During a European multicenter clinical study, 19 patients were
implanted at MHH since February 1997. No significant complications occurred.
RESULTS: In all patients, postoperative unaided pure tone threshold was unaltered
in comparison with the preoperative recordings. The use of the audio processor
leads to a significant functional gain, particularly in the high frequencies. The
patients report about undistorted hearing resulting in a better speech
understanding even in situations with loud background noise. CONCLUSION: The
preliminary results show a promising new approach to the use of hearing
prostheses for patients suffering from moderate to severe sensorineural hearing
loss.
PMID- 9644673
TI - [Rhinosurgical concept in management of fronto-basal defects with cerebrospinal
rhinorrhea].
AB - BACKGROUND: Cerebrospinal fluid (CSF) leak, with its potential infectious
complications remains today a challenge in diagnosis and surgical treatment. With
the introduction of endonasal microsurgery, new minimally invasive techniques for
the repair of these defects have been pioneered. Nasal approaches to the anterior
skull base include external-transfacial as well as endonasal approaches for
reconstruction. It is important to have multiple possible approaches for the
correction so that the optimal method for the individual pathology may be
selected. The purpose of this paper is to clarify the decision process for
selecting the safest procedure with the least possible morbidity and functional
compromise. METHOD: In a retrospective study we assessed a group of 69 patients
treated from 1988 to 1996. Patient records, CT scans, postoperative clinical
follow-up and a questionnaire, sent to the patients, were evaluated. The various
external and endonasal approaches are presented and the closure techniques are
discussed in detail. RESULTS: Of the 69 operations, 40 (58%) were external and 29
(42%) were endonasal. There were three failures in the external approach group
(4.4%) and no failures in the endonasal group. No major complications in the
intraoperative or postoperative course occurred. Of importance, olfaction was
retained in 94% of patients in at least one side. The average duration of
hospitalization was 6 days. CONCLUSIONS: Nasal approaches to the anterior skull
base for treatment of CSF leaks are highly effective, safe, and cause minimal
morbidity. The optimal surgical approach is chosen according to the precise
location and extent of the defect. We are now increasing using endonasal
microsurgical approaches. The open, transfacial approaches are still indicated
for fractures of the posterior wall of the frontal sinus as well as larger multi
fragmented fractures of the anterior skull base.
PMID- 9644674
TI - [Effect of adenoid hyperplasia on nasal airflow].
AB - BACKGROUND: Adenoid hyperplasia is one of the most common reasons for nasal
obstruction in childhood. The consequences of a nasopharyngeal obstruction on the
airflow in the nasal cavity and the epipharynx were investigated. MATERIALS AND
METHODS: In a model of a nose we conducted experiments with adenoids of different
size, documenting their influence on inspiratory and expiratory nasal flow.
Rhinoresistometry was performed to obtain further information concerning
resistance and turbulence. RESULTS: The flow experiments showed no alterations of
the inspiratory nasal flow regardless of adenoid size. Instead the adenoid had a
significant influence on the direction of the expiratory nasal flow in the
cavity. Depending on the extension of the hyperplasia, parts of the nasal cavity
were excluded from the flow. Rhinoresistometry showed that relation between
nasopharyngeal obstruction and nasal resistance was nonlinear. CONCLUSION:
Adenoid hyperplasia affects only expiratory nasal flow. In our model a critical
mass seemed to be reached in case of more than 60% nasopharyngeal obstruction. A
narrowing of the epipharynx up to 50% of its volume has no significant effects on
nasal resistance.
PMID- 9644675
TI - [Computer-assisted surgery in the ENT specialty. Developments and experiences
from the first decade].
AB - BACKGROUND: Computer-Assisted-Surgery (CAS) names a method that allows
intraoperative navigation in the surgical field based on digital image data like
CT, MRT, MRA, DSA and others. A computer processes the image data in real time
and is intraoperatively connected to a measuring system for coordinate
determination. CAS is used in ENT surgery since 1986. The authors developed
several generations of CAS systems. METHODS: In a first approach, a passive robot
arm was applied. Self-developed electromechanical and infrared optical coordinate
measuring devices followed. RESULTS: CAS was applied to several fields of
otorhinolaryngologic surgery including the paranasal sinuses, the orbit, the
rhinobasis and otobasis and other. CAS was found to be useful for surgery of
acoustic neuromas, the paranasal sinuses in cases of massive disease or revision
surgery, decompression of orbit or optiv nerve, extraction of deep seated foreign
bodies, stereotaxy-like biopsies, for educational purposes and others.
CONCLUSIONS: CAS in its current state of development is a useful tool that can be
routinely applied. However, further technical development is necessary.
PMID- 9644676
TI - [Surgery in benign parotid tumors: individually adapted or standardized radical
interventions?].
AB - BACKGROUND: Several authors demand emphatically that the minimal operative
procedure in benign parotid gland tumors has to be a superficial parotidectomy.
MATERIAL: Of a consecutive series of 372 patients with benign parotid tumors
treated in our department between 1973-1996 81% of the patients could be followed
up 1-24 years. in 10.9% a total parotidectomy was performed, in 16% a lateral
parotidectomy and in 73.1% a simple extirpation of the tumor (often taking away a
small margin of surrounding parotid parenchyma). The operating microscope and
microsurgical techniques were used in all of these operations. RESULTS: Of all
the followed-up patients 2.3% developed a recurrence. There were no recurrences
of cystadenolymphomas or of rare types of adenomas. Recurrences of primary
treated pleomorphic adenomas occurred in 3.0%. In recurrent pleomorphic adenomas
a further recurrence could be seen in 7.4% of the cases. The over-all incidence
of permanent facial nerve weakness was 2.1%: 0.7% after extirpation, 3.3% after
lateral parotidectomy and 9.7% after total parotidectomy. we observed in 6.3% a
gustatory sweating. CONCLUSION: Our data prove that with simple extirpation
similar results compared to lateral parotidectomy can be achieved concerning
recurrence, function of the facial nerve and the Frey's syndrome. We suggest a
surgical management adapted to the extent, the size and the location of the
parotid gland tumors. In our opinion lateral or total parotidectomy should be
reserved for tumors of larger amount or deep located tumors.
PMID- 9644677
TI - [Possible application of a signal enhancer for duplex ultrasound in
otorhinolaryngology].
AB - BACKGROUND: Vascularization is a characteristic of malignant tumor growth. It is
possible to distinguish between benign and malignant tumors and lymph nodes of
the head and the neck by their pattern of blood vessels which can be detected by
color image ultrasonography. Unfortunately this detection is often unsuccessful
because the vessels are too small. METHOD: Four cases (lymph node metastasis,
chronic lymph node inflammation, Morbus Hodgkin, cancer of the floor of the
mouth) are demonstrated. The vascularization of the masses was detected before
and after the injection of Levovist, a contrast agent which is known to amplify
the duplex signal up to 25 dB. RESULTS: In all of the demonstrated cases, a
similar pattern of intranodal vessels was detected before the application of
Levovist. After the injection an enhancement of the duplex signal could always be
detected within the first minute and differences of the intratumoral pattern of
the blood vessels between the cases could be identified. DISCUSSION: Levovist
results in an increased detection of intratumoral blood vessels detected by color
image ultrasonography. Further studies are necessary to check whether its
application results in an increase of the specificity of the examination.
PMID- 9644678
TI - [Interesting case no. 12. Rhabdomyosarcoma of the petrous bone with infiltration
of the facial nerve].
PMID- 9644679
TI - [History of diaphanoscopy. Pictures from the history of otorhinolaryngology,
illustrated by instruments from the collection of the Ingolstadt German Medical
History Museum].
AB - BACKGROUND: In 1854 the Spanish singing teacher Manuel Garcia succeeded in
inspecting his own larynx. In 1857 the neurologist Ludwig Turck in Vienna,
without knowledge of Garcia's achievement, had been experimenting on laryngoscopy
with his patients using a small mirror and sunlight. When in the winter of 1857
1858 he had to suspend his experiments for lack of sunlight, he lent his mirror
to physiologist Johann Czermak in Budapest. Czermak, using artificial light
reflected by a perforated mirror, developed modern laryngoscopy within a few
weeks and made it a clinically valuable method. He described it in March 1858 as
his own invention. This was the beginning of a an embittered fight with Turck
about whose development had priority. DIAPHANOSCOPY OF THE LARYNX: During his
very first studies on laryngoscopy Czermak noticed that the interior of the
larynx could be inspected very well when the neck was illuminated by a strong
light from without and the mirror was held in the dark pharynx. The tissue would
then appear transilluminated in a glowing deep red. When sufficiently bright
electric lamps became available in 1889, Rudolph Voltolini in Breslau, Germany,
took up the transillumination of the larynx and even carried out some minor
intralaryngeal operations using this method. Although suitable diaphanoscopes
were soon on the market this technique was not widely adopted. It was ony used
once in 1954 (Pellnitz et al.) for diagnosing early stages of laryngeal cancer.
DIAPHANOSCOPY OF THE PARANASAL SINUSES: Voltolini in Breslau and Cozzolino in
Naples experimented independently of each other with small electric lamps with
the aim of finding new techniques of rhinoscopy. Both of them placed their lamp
in the nasopharynx and performed anterior rhinoscopy using an ordinary speculum.
However, it was only Voltolini who noticed the transillumination of the maxillary
sinuses when the lamp was placed in the oral cavity. On October 29, 1888, in
Breslau he demonstrated diaphanoscopy of the maxillary sinus for the first time.
Cozzolino claimed that he had introduced this technique prior to Voltolini.
Voltolini had died in 1889 and could not comment on this. A careful study of the
original publications, however, shows that Cozzolino had only inspected the nasal
cavity with retronasal illumination, but had not demonstrated the maxillary sinus
by transillumination. The diaphanoscopy of the paranal sinuses was very soon
elaborated to perfection: Vohse in 1890 applied it to the frontal sinuses, Gerber
in 1900 invented a double diaphanoscope for examining both frontal sinuses
simultaneously. Although the shortcomings of diaphanoscopy soon became apparent,
the method was widely used for about half a century, but in the end could not
compete with modern techniques of radiography and ultrasound. The history is
related in detail and illustrated with numerous figures.
PMID- 9644680
TI - [Restorative interventions of the tympanic membrane and mastoid. II].
PMID- 9644681
TI - M. D. Anderson initiates aggressive ovarian cancer screening program.
PMID- 9644682
TI - Chemotherapy may improve quality of life of patients with incurable cancer.
PMID- 9644683
TI - Extraovarian primary peritoneal carcinoma.
AB - Extraovarian primary peritoneal carcinoma (EOPPC), a relatively newly defined
disease that develops only in women, accounts for approximately 10% of cases with
a presumed diagnosis of ovarian cancer. Characterized by abdominal
carcinomatosis, uninvolved or minimally involved ovaries, and no identifiable
primary, EOPPC has been reported following bilateral oophorectomy performed for
benign disease or prophylaxis. Most cases are of serous histology; however,
nonserous tumors have been observed. Although EOPPC is similar to serous ovarian
carcinoma with respect to clinical presentation, histologic appearance, and
response to chemotherapy, molecular and epidemiologic studies have indicated that
it may be a separate entity. This review explores the clinical presentation,
management, prognosis, and survival of EOPPC.
PMID- 9644684
TI - Salvage therapy for ovarian cancer.
AB - Patients with epithelial ovarian cancer must receive optimal surgical care and
state-of-the-art chemotherapy in the primary treatment setting. The salvage
treatment of women with recurrent or persistent ovarian cancer remains a
difficult task. A very small percentage of patients with platinum-sensitive,
small-volume disease appear to achieve prolonged disease-free survival. The
treatment of patients with larger-volume disease (> 0.5 cm) or platinum-resistant
disease remains largely palliative. The plethora of available new agents has
provided the physician with multiple options for salvage chemotherapy. Although
cure in the salvage setting is not often achieved currently, palliative treatment
allows many patients to live painfree, productive lives. Candidates for salvage
therapy may be grouped into one of several categories, which reflect different
prognoses for response. These categories include refractory disease (defined as
progressive tumor during primary treatment), persistent disease (a partial
response to primary therapy followed by elevated tumor markers or clinically
evident persistent disease), and recurrent disease (initial complete response to
primary therapy with subsequent relapse). Categorizing patients into these
categories provides a systematic method for organizing the administration of
salvage chemotherapy.
PMID- 9644685
TI - Clinical trials referral resource. Clinical trials of multimodality approaches
for advanced esophageal cancer.
PMID- 9644686
TI - The challenge of designing clinical trials for AIDS-related Kaposi's sarcoma.
AB - Kaposi's sarcoma (KS) is a frequent cause of morbidity and mortality in patients
with human immunodeficiency virus (HIV) infection. Several characteristics of KS
pose challenges for the conduct of clinical trials. Kaposi's sarcoma patients
often have multiple, irregularly shaped lesions, making accurate assessment of
tumor size difficult. The lesions may have varying degrees of nodularity.
Involvement of the lung or other visceral organs often consists of multiple
irregular lesions. Conventional oncology staging systems cannot be applied
effectively to KS because there is no clear primary lesion. Kaposi's sarcoma is
affected by the status of the underlying HIV infection, and there are reports of
KS lesions regressing in response to effective antiretroviral therapy. A system
for staging and response assessment in KS, developed by the AIDS Clinical Trials
Group (ACTG), has proven to be a useful tool for the conduct of trials in KS. A
newer system that also attempts to assess patient benefit in response to therapy
is now being developed by the National Cancer Institute, FDA, and AIDS Malignancy
Consortium. These tools, as well as careful methodology in the conduct of
clinical trials, should help optimize the clinical development and evaluation of
new therapies for KS.
PMID- 9644687
TI - Variations in charges for two major breast cancer surgeries, U.S., 1996.
AB - In 1996, the total in-hospital charges for the primary treatment of women with
breast cancer with a modified radical mastectomy averaged $10,000 throughout the
United States. The total charge (hospital plus physician's fees) varied by 95%
between the high charge reported in New York ($12,690) and the low charge in
Michigan ($6,510). The hospital portion of the bill averaged 65% of the total and
ranged from 51% in New York to 74% in Virginia. The average length of stay for
these women was 2.39 days and ranged from 3.18 days in New York to 1.69 and 1.66
days in Washington and Arizona, respectively. The average charge for a partial
mastectomy was $8,760, with notable variations between states. The Texas total
charge was the highest ($12,890, some 47% above the US norm) and more than twice
the low charge in Ohio ($6,080, 31% below the US average). The physicians'
charges averaged $3,330 for the country as a whole and accounted for 38% of the
bill. This proportion ranged from 46% of the total in New York to 70% in Indiana
and Colorado. The average length of hospitalization for a partial mastectomy was
1.84 days. On average, women remained in the hospital for the longest time in New
Jersey (2.78 days) and for the shortest time in Oregon and Massachusetts (1.40
days and 1.45 days, respectively).
PMID- 9644688
TI - Stereotactic breast biopsy: indications and results.
AB - Imaging-guided breast biopsy performed with large-core needles can accurately
diagnose most breast pathologies, often allowing a diagnosis to be made more
quickly and less expensively than with surgical biopsy. Major complications, such
as hemorrhage and infection, are extremely rare, although post-biopsy ecchymosis
and tenderness are not unusual. Because less tissue is removed, post-biopsy
cosmetic deformity does not occur. Stereotactic biopsy is performed by
triangulating the position of a breast lesion and by obtaining views angled
equally off a central axis. This can be done using dedicated tables or add-on
equipment. Stereotactic core biopsy has a reported accuracy of at least 90%. All
lesions for which biopsy would ordinarily be recommended are amenable to
stereotactic techniques, but those near the chest wall or in the axilla may be
more difficult to biopsy with some equipment. Lesions characterized by
calcifications are sometimes more difficult to sample. A biopsy diagnosis of
ductal atypia, because of its histologic heterogeneity, requires surgical
excision to exclude coexistent carcinoma, which has been found in half of women
at subsequent surgical excision. A core biopsy diagnosis of ductal carcinoma in
situ does not preclude the discovery of invasive carcinoma at surgery. In rare
instances, the small tissue volume removed at stereotactic biopsy does not permit
a final diagnosis to be made; this occurs most commonly when differentiating
phyllodes tumor from fibroadenoma.
PMID- 9644689
TI - Local excision for rectal cancer: an uncertain future.
AB - Adenocarcinoma of the rectum remains a significant public health challenge, with
39,000 new cases and 8,500 deaths predicted for 1998. Radical surgery, the
current standard therapy, frequently necessitates the formation of a permanent
colostomy and is associated with significant morbidity. For these reasons,
alternatives to radical surgery have been sought. This review focuses on
sphincter-sparing surgical modalities for distal rectal cancer. An extensive
review of the literature on local excision alone, local excision plus
postoperative radiation therapy (with or without chemotherapy), and local
excision following preoperative chemoradiotherapy is presented. The design and
interim results of the sole prospective multi-institution trial of local
excision, Cancer and Leukemia Group B trial 8984, are also summarized. The
literature on this subject, which is dominated by single-institution,
retrospective reports, fails to support local excision as a superior or equal
therapy to radical surgical excision for invasive distal rectal adenocarcinoma.
The crucial question regarding the efficacy of radical surgical salvage for local
recurrence following local excision also remains unanswered. We conclude that the
role of local excision for invasive distal rectal adenocarcinoma remains
undefined. If there is a future for this therapeutic modality, it will depend
significantly on rigorous patient selection, provided that the efficacy of
radical surgical salvage for local recurrence can be established.
PMID- 9644690
TI - Remembering not to forget.
PMID- 9644691
TI - Cancer pain management.
PMID- 9644692
TI - Medical oncology services in the nonacute setting.
PMID- 9644693
TI - Developing an oncology internship program.
PMID- 9644694
TI - Use of scopolamine to improve care of patients who are terminally ill.
PMID- 9644695
TI - Hospital-wide education on venous access devices.
PMID- 9644696
TI - Elimination of frequent vital sign monitoring in patients receiving paclitaxel.
PMID- 9644697
TI - Bereavement program helps to meet families' needs.
PMID- 9644698
TI - Success in starting peripheral lines.
PMID- 9644699
TI - Beyond body image: the experience of breast cancer.
AB - PURPOSE/OBJECTIVES: To describe the mental and emotional impact of treatment for
breast cancer with a focus on the ways the body is experienced. DESIGN:
Phenomenologic, descriptive, and interpretive. SETTING: An outpatient treatment
area of a comprehensive cancer center in the southwestern United States. SAMPLE:
20 women, ages 20-68 (mean = 50 years), who had mastectomies (including both
modified radical mastectomies and lumpectomies, with some having reconstruction)
for breast cancer. METHODS: Content analysis of verbatim transcriptions of open
ended interviews using hermeneutic phenomenology and descriptive and interpretive
presentation of a paradigm case. MAIN RESEARCH VARIABLES: Reaction to breast
cancer and its treatment. FINDINGS: Informants' descriptions demonstrate that the
body can be viewed as having three aspects: (a) the body as symbol or social
expression (i.e., how bodies make a social statement and tell others who you
are); (b) the body as a way of being in the world, including sensations and
symptoms such as nausea, fatigue, and pain; and (c) the existential sense that
one needs a body to be in the world (i.e., the body expresses existence), which
led to more awareness of the possibility of death. CONCLUSIONS: Women treated for
breast cancer view their bodies in ways that go beyond what is suggested by the
literature on body image and breast cancer, encompassing a wide range of
responses. IMPLICATIONS FOR NURSING PRACTICE: The contribution of this study is
the documentation of the complexity of the meaning of "body" for women with
breast cancer. Appropriate interventions differ for each aspect of the body: for
the body as social symbol, programs such as Look Good ... Feel Better or image
centers; for the body's sensations and symptoms, information about what to expect
and about symptom prevention and management; for the existential body, active
listening to fears and concerns and providing assistance as needed.
PMID- 9644700
TI - Osteoporosis: a concern for cancer survivors.
AB - PURPOSE/OBJECTIVES: To describe the risk factors, prevention, diagnosis,
management, and impact of osteoporosis on the lives of women who have survived
breast and endometrial cancer. DATA SOURCES: Journal articles, selected
textbooks, prescribing information, and conference proceedings. DATA SYNTHESIS:
Women who have not been able to have estrogen-replacement therapy (including
women who have survived breast and endometrial cancer) are at higher risk for
developing osteoporosis. Osteoporosis is associated with significant medical
costs and can have a detrimental effect on long-term quality of life (QOL) as
well as increased mortality. Recently, significant advances have been made in the
ability to detect and manage osteoporosis. CONCLUSIONS: Thorough assessment,
appropriate evaluation, and treatment of osteoporosis can reduce the
complications of this condition and ultimately improve the QOL for women
surviving cancer. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses should
include assessment of risk for osteoporosis into their practice. Education about
the prevention of osteoporosis should be included with other wellness education.
Women at higher risk for the development of osteoporosis should be referred for a
diagnostic evaluation. Oncology nurses can provide women with osteoporosis with
education about treatment as well as psychosocial support.
PMID- 9644701
TI - Cancer-related diarrhea: a neglected cause of cancer-related symptom distress.
PMID- 9644702
TI - Cancer-related diarrhea: selected findings of a national survey of oncology nurse
experiences.
AB - PURPOSE/OBJECTIVES: To describe oncology nurse experiences with disease- and
treatment-related diarrhea in patients with cancer, including assessment methods
and pharmacologic/supportive care. DESIGN: Descriptive. SAMPLE/SETTING: 1,288
(26%) of 5,000 randomly selected Oncology Nursing Society members employed full
time in adult clinical settings in the United States. METHODS: Mailed survey with
scannable booklets. MAIN RESEARCH VARIABLES: Nurse perceptions of disease and
treatment-related issues associated with diarrhea in patients with cancer, along
with currently used assessment criteria and nursing care. FINDINGS: Nurses in
this sample routinely encounter diarrhea in their patients with cancer. They
commonly assess/document diarrhea by noting its presence or absence, with a
minority of nurses using a rating tool. When indicated, most nurses prepare
patients for probable diarrhea. This preparation includes both verbal and written
instructions about diet, skin care, drug therapy, and treatment of severe
diarrhea. Nurses report that primary drug therapy for diarrhea consists of over
the-counter agents. Supportive care consists of fluid/electrolyte replacement,
skin care and diet modifications, and also bowel rest and parenteral nutrition
for severe diarrhea. For these nurses, the most important factors influencing
choice of management strategies are symptom relief and physician and patient
preference. CONCLUSIONS: Although the majority of nurses in this study report
providing anticipatory guidance, patient education, and supportive diarrhea
management, they are not assessing diarrhea systematically. They report common
use of nonprescription medications, with pharmacologic interventions varying with
severity of diarrhea. IMPLICATIONS FOR NURSING PRACTICE: Targeted education is
needed to help nurses implement systematic assessment and documentation. Efficacy
of diarrhea-management strategies and protocols must be tested-specifically,
optimal timing and types of skin care, dietary changes, and bowel rest.
PMID- 9644703
TI - Octreotide in the management of diarrhea induced by graft versus host disease.
AB - PURPOSE/OBJECTIVES: To evaluate the potential benefit of the somatostatin
analogue, octreotide, for the management of diarrhea induced by graft versus host
disease (GVHD). DATA SOURCE: Pilot clinical trial involving 21 patients
undergoing allogeneic transplant with positive histologic or radiographic
evidence of GVHD of the gastrointestinal tract who failed antidiarrheal therapy
with loperamide. DATA SYNTHESIS: A complete response, defined as resolution of
diarrhea, was seen in 71% of trial participants (15 of 21 patients). At the dose
and scheduling used (500 mcg i.v. three times daily for a median of seven
consecutive days), octreotide was extremely well tolerated in all patients.
CONCLUSIONS: In this pilot study, octreotide treatment was effective in reducing
the amount of diarrhea in patients with acute GVHD. The data suggest that
patients receiving octreotide early in the course of the diarrhea experienced
more benefit than patients with persistent diarrhea prior to receiving
octreotide. The demonstrated safety and efficacy of octreotide in this patient
population support further investigation of this therapeutic strategy for GVHD
induced diarrhea. A randomized, controlled, clinical trial of octreotide versus
loperamide for the initial treatment of GVHD-induced diarrhea is warranted.
IMPLICATIONS FOR NURSING PRACTICE: Octreotide should be administered early in the
course of GVHD as soon as onset of diarrhea is noted and should be discontinued
as soon as diarrhea resolves to avoid constipation and the potential development
of an ileus. Because response to the drug usually occurs quickly, maintaining
treatment for additional days or weeks is unnecessary. If a benefit is not seen
in four to seven days, continuing octreotide therapy is neither cost-effective
nor prudent.
PMID- 9644704
TI - The nurse's role in diarrhea management.
AB - PURPOSE/OBJECTIVES: To discuss the causes, clinical manifestations, and
consequences of diarrhea in the patient with cancer; to describe the oncology
nurse's role in the assessment, management, and treatment of cancer-related
diarrhea. DATA SOURCES: Synthesis of published peer-reviewed data, professional
experience. DATA SYNTHESIS: The many causes of cancer-related diarrhea include
specific types of cancer and specific anticancer treatment regimens (e.g.,
chemotherapy, radiotherapy). Poorly controlled diarrhea may result in a range of
physiologic and psychological effects that extend beyond the patient to
significant others and caregivers. Comprehensive assessment of diarrhea is the
foundation for the appropriate use of pharmacologic and supportive therapies.
CONCLUSIONS: Diarrhea, much like fatigue, is a symptom that only recently has
become a focus of oncology nursing research and focused intervention.
IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can significantly influence
the quality of care given to patients who develop diarrhea as a symptom of cancer
or as a sequela of cancer therapy. As such, oncology nurses are challenged to
maintain current knowledge of the causes and available treatment strategies for
cancer-related diarrhea. Nurses need to rely on their experiential skill and a
working knowledge of published research to identify patients at risk. They also
must communicate effectively with patients and caregivers in every practice
setting about the nature of diarrhea and its causes, as well as develop
appropriate interventions for each individual.
PMID- 9644705
TI - Quality of life in breast cancer survivors: implications for developing support
services.
AB - PURPOSE/OBJECTIVES: Quality of life (QOL) is becoming more important in regard to
breast cancer as treatment advances extend the period of survivorship. The
purpose of this article is to share the results of a cancer center's attempt to
evaluate the QOL needs of breast cancer survivors in order to provide improved
supportive-care services. DESIGN: Descriptive mailed survey. SETTING: A medical
center in southern California. SAMPLE: A random sample of breast cancer survivors
(N = 298). METHODS: Breast cancer survivors completed a mailed survey that
included major outcome variables of QOL and pain. Subjects were stratified by
three age groups: younger than 40 years, 40-60 years, and older than 60 years.
MAIN RESEARCH VARIABLES: QOL subscales (physical, psychological, social, and
spiritual well-being) and overall QOL score and pain as assessed by the Brief
Pain Inventory. FINDINGS: Results indicated continued physical demands of breast
cancer, including fatigue and pain, as well as psychological burdens related to
fear of breast cancer recurrence and anxiety. The social well-being domain
indicated some unique aspects of QOL when applied to breast cancer survivorship
such as the fear of breast cancer in female relatives. The spiritual well-being
domain illustrated the unique QOL aspects of life-threatening illness such as
living with uncertainty and maintaining hope. Breast cancer survivors also
reported positive aspects and life changes after successfully facing breast
cancer. CONCLUSIONS: Breast cancer survivors experience many demands of illness
across the physical, psychological, social, and spiritual domains. IMPLICATIONS
FOR NURSING PRACTICE: The study's findings can be useful in directing cancer
centers' efforts to provide comprehensive care for breast cancer survivors.
Nurses play a critical role in leading these efforts for supportive-care services
intended to improve the QOL of breast cancer survivors.
PMID- 9644706
TI - The effectiveness of a nurse-managed minimal smoking-cessation intervention among
hospitalized patients with cancer.
AB - PURPOSE/OBJECTIVES: To determine the effectiveness of a nurse-managed minimal
smoking-cessation intervention among hospitalized patients with cancer. DESIGN:
Prospective, two-group, randomized clinical trial. SETTING: Urban, academic,
tertiary-care setting. SAMPLE: 28 adult male and female smokers with a diagnosis
of cancer who are hospitalized for a surgical procedure. METHODS: During
hospitalization, subjects were assigned to a minimal smoking-cessation
intervention group (n = 14) or a usual care group (n = 14). Verification of
smoking status was performed at a clinic visit six weeks postintervention.
Nonsmoking status was defined as self-report of zero cigarettes/day during the
prior week and confirmed by saliva cotinine analysis. MAIN RESEARCH VARIABLES:
One-time, Inpatient, nurse-managed, minimal smoking-cessation intervention, self
reported smoking status, and saliva cotinine level of < or = 14 ng/ml. FINDINGS:
Upon hospital admission, 64% of the intervention group and 71% of the usual care
group reported their intention to quit smoking. At six weeks postintervention,
only 21% and 14% of the intervention and usual care group, respectively, were
classified as abstinent from smoking. More than 90% of the intervention group
members who resumed smoking did so within first week of discharge. IMPLICATIONS
FOR NURSING PRACTICE: A more intensive intervention may be necessary to assist
hospitalized surgical patients in achieving smoking cessation. Additional contact
prior to discharge or within the first few days postdischarge may be necessary to
reinforce strategies for remaining abstinent.
PMID- 9644707
TI - Changing i.v. administration sets: is 48 versus 24 hours safe for neutropenic
patients with cancer?
AB - PURPOSE/OBJECTIVES: To examine the effects of changing i.v. administration sets
at 48 versus 24 hours on the incidence of infusion-related septicemia in
neutropenic patients with cancer. DESIGN: Prospective, randomized clinical trial
with repeated measures. SETTING: Large urban cancer center. SAMPLE: 50 adult
inpatients with a primary diagnosis of hematologic malignancy, breast cancer, or
testicular cancer or who were receiving a stem cell transplant. METHOD: Subjects
were assigned randomly to have their i.v. sets changed every 48 or 24 hours.
Subjects continued in the study for a maximum of five measurements, until they
were no longer neutropenic, or until transferred or discharged from the hospital.
MAIN RESEARCH VARIABLES: Rates of infusate colonization, microorganisms
identified, incidence of infusion-related septicemia. FINDINGS: Colonized
infusate was detected in 18 (5%) of 413 i.v. sets; 9 (5%) of 177 sets were
changed at 48 hours, and 9 (4%) of 236 sets were changed at 24 hours (p > 0.05).
A trend toward increased colonization of i.v. sets used to administer parenteral
nutrition (19%) and, to a lesser extent, electrolytes (9%) was identified in the
48-hour group. Coagulase-negative staphylococci were the most frequently isolated
microorganisms in the i.v. infusate. Similar organisms were isolated from blood
cultures and administration sets, however, no subject had identical organisms
isolated from both i.v. infusate and blood cultures. No subject with colonized
infusate developed infusion-related septicemia. CONCLUSIONS: No difference
existed in the incidence of colonization or infusion-related septicemia between
subjects whose i.v. administration sets were changed at 48 versus 24 hours.
IMPLICATIONS FOR NURSING PRACTICE: Changing i.v. administration sets every 48
hours is recommended. Exceptions to this include i.v. administration sets used to
administer blood products and total parenteral nutrition.
PMID- 9644708
TI - Differences in fatigue by treatment methods in women with breast cancer.
AB - PURPOSE/OBJECTIVES: To investigate the differences between various cancer
therapies (radiation, hormonal, chemotherapy, and their combinations) and the
specific dimensions of fatigue (affective meaning, behavioral/severity,
cognitive/mood, and sensory). DESIGN: Descriptive, cross-sectional, mailed survey
design. SAMPLE AND SETTING: Data were collected from women who were breast cancer
survivors and members of a nonprofit educational organization in the North-east.
Criteria for this study included no self-reported disease recurrence, and
treatment was within 18 months prior to the mailed survey (N = 322). The typical
participant was middle-aged (mean = 52.2; SD = 10.3), Caucasian (93%),
postmenopausal (55%), and diagnosed with cancer 2.42 (SD = 2.6) years prior to
the study. METHODS: Secondary data analysis from a study using the Piper Fatigue
Scale. VARIABLES: Level of fatigue. FINDINGS: Significant differences were found
by treatment in total fatigue scores (p < 0.03) and cognitive/mood scores (p <
0.05). Women who received combination therapy had the highest fatigue scores
(mean = 4.8; SD = 2.0); those who received only radiation therapy had the lowest
fatigue scores (mean = 2.7; SD = 2.0). CONCLUSIONS: Fatigue in breast cancer
survivors varies by type of cancer therapy. Future studies are needed to
investigate the relationships between fatigue and hormonal therapy, and they need
to be designed to examine changes over time. IMPLICATIONS FOR NURSING PRACTICE:
Study findings advance knowledge about fatigue in women with breast cancer and
aid nurses in providing anticipatory guidance for women undergoing different
treatment regimens.
PMID- 9644709
TI - Patient management strategies for interferon alfa-2b as adjuvant therapy of high
risk melanoma.
AB - PURPOSE/OBJECTIVES: To review results of Eastern Cooperative Oncology Group
(ECOG) trial E1684 in the context of nursing issues concerning interferon alfa-2b
(IFN alpha-2b) as adjuvant therapy for high-risk melanoma. DATA SOURCES:
Published results of ECOG trial E1684 and additional safety data provided by the
trial sponsor. Selection of material was based on information that would expand
on published safety results and present patient-management strategies relevant to
oncology nurses. DATA SYNTHESIS: High-dose IFN alpha-2b significantly prolonged
median relapse-free survival (< 0.01) and overall survival (p = 0.047), but side
effects required extensive nursing interventions. With appropriate patient
management, including dose modifications, 74% of patients who did not relapse
received a full course of therapy. CONCLUSIONS: Adjuvant, high-dose IFN alpha-2b
can significantly prolong relapse-free and overall survival in patients with high
risk melanoma, but nursing interventions are required to ensure patient
compliance. IMPLICATIONS FOR NURSING PRACTICE: Accurate nursing assessment and
appropriate interventions can help patients safely complete this effective
adjuvant therapy.
PMID- 9644710
TI - [Effect of immobilization on yeast metabolism].
AB - Respiratory quotients and enzyme activity were determined in yeast cultures of
Saccharomyces cerevisiae and Kluyveromyces sp., both suspended and immobilized on
acrylonitrile fibers. Immobilization induced changes in the cell metabolism
resulting in activation of the basic metabolic pathway of the given type of yeast
cells.
PMID- 9644711
TI - [Biosynthesis and isolation of a recombinant protein for producing genetically
engineered human proinsulin].
AB - Isolation of the recombinant protein from a genetically engineered Escherichia
coli 1854 producer for further chemical enzymatic transformation into human
insulin through proinsulin was studied. Under optimal conditions, the recombinant
protein formation was more than 35% of the total cell proteins. Structures of the
polypeptides obtained and purified chromatographically were confirmed by amino
acid analysis. Human proinsulin was derived from the recombinant protein
isolated.
PMID- 9644712
TI - [Stimulating effect of triphenylmethane series dyes on growth of Escherichia coli
bacteria].
AB - The stimulating effect of a dye of the triphenylmethane group (fast green)
applied at low concentrations (10(-4)%) in the presence of toluene on the
specific growth rate of bacteria was found. The cell size did not change during
batch cultivation. However, the cell dry weight and zeta-potential increased
sharply.
PMID- 9644713
TI - [Potentiometric electrodes for determining choline, butyrylcholine and
cholinesterase inhibitors].
AB - Potentiometric choline electrodes were developed on the basis of the mediator
free bioelectrocatalysis. The electrodes made of a composite carbon-polymer
material contain choline oxidase and peroxidase coimmobilized on the surface of
the electrode. The rate of the potential increase was shown to be proportional to
the choline concentration within a broad range of variation. Coupling of choline
sensitive electrodes with butyrylcholinesterase makes possible both the direct
detection of butyrylcholine and analysis of butyrylcholinesterase inhibitors.
PMID- 9644714
TI - In vitro effect of bacterial lipopolysaccharide on the cytotoxicity of human
natural killer cells.
AB - Preincubation with a number of mediators of infection, such as Gram negative
bacteria (S. typhi), bacterial lipopolysaccharide (LPS), tumor necrotic factor
alpha (TNF-alpha), and interleukin-2 (IL-2), significantly increases natural
killer (NK) cell activity in samples of human peripheral blood mononuclear cells
(PBMC), without changing the levels of either the phenotypic CD16/56 or
stimulatory CD25 marker. We now report similar results after preincubation of
highly purified NK cell preparations (CD16 + 56 > 95%; the rest corresponding to
CD3+ T-cells) with either S. typhi, TNF-alpha or IL-2. However, in similar
experiments, LPS inhibits, in a dose-dependent manner (final conc. 2.5, 5.0 or
10.0 micrograms/mL), NK cell cytotoxicity against K-562 tumor cells.
Preincubation of purified NK cells with LPS (25 micrograms/mL; 10 and 30 min)
produced significant alterations in the tyrosine
phosphorylation/dephosphorylation pattern of several intracellular proteins,
including a significant increase (10 min) in the phosphorylation of the 120; 100;
72 and 59 kDa proteins, followed (30 min) by the essentially complete
desphosphorylation of the p59 protein. Qualitatively similar results were
obtained at lower LPS concentrations e.g., range 2.5 to 20 micrograms/mL. The
absence of phosphoproteins in the 40-44 kDa range, known to be present after
incubation of monocytes with LPS, raises the possibility that these "class" of
proteins may be critical in explaining the LPS inhibitory effect on NK lytic
function. Our finding may contribute to a better understanding of the mechanisms
involved in the complex in vivo interaction between LPS, monocytes and NK cells.
PMID- 9644715
TI - Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450
reductase coexpressed in insect cells using baculovirus.
AB - Human fetal CYP3A7 and human NADPH-cytochrome P450 reductase were coexpressed in
insect cells, TN-5, infected with a recombinant baculovirus carrying both cDNAs.
The expression of reductase in TN-5 cells was shown to be sufficient for the
CYP3A7 dependent 16 alpha-hydroxylation of dehydroepiandrosterone. However, the
extra addition of cytochrome b5 and phospholipid was necessary to obtain a
maximal activity of CYP3A7 catalyzing the reaction. CYP3A7 expressed in TN-5
cells was capable of metabolizing testosterone, cortisol and
dehydroepiandrosterone 3-sulfate as well as dehydroepiandrosterone. The apparent
Vmax for 6 beta-hydroxylations of testosterone was similar to that obtained for 6
beta-hydroxylation of cortisol (2.9 versus 2.5 nmol/nmolP450/min). In contrast,
the apparent Vmax for 16 alpha-hydroxylation of dehydroepiandrosterone and its 3
sulfate were 20 and 2 times greater than those observed for steroid 6 beta
hydroxylations, respectively (67.5 and 5.8 versus 2.5-2.9 nmol/nmol P450/min). On
the other hand, the apparent K(m) for 6 beta-hydroxylations of testosterone and
cortisol were greater than those for 16 alpha-hydroxylations (120 and 860 versus
46-58 microM). Thus, CYP3A7 was active for steroid 6 beta-hydroxylations and 16
alpha-hydroxylations, but there were greater differences in Vmax/K(m) ratios
between these reactions.
PMID- 9644716
TI - Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after
intravenous administration to rabbits.
AB - The pharmacokinetics of 2-(allylthio)pyrazine (2-AP) were evaluated after
intravenous administrations of the drug to rabbits. The reason for the multiple
peaks in the plasma concentration of 2-AP after intravenous administration of the
drug to rabbits were also investigated. After intravenous administration of 2-AP,
10, 20, and 50 mg/kg, to rabbits, the pharmacokinetic parameters of 2-AP, such as
the total area under the plasma concentration-time curve from time 0 to 12 h
(261, 672, and 1190 micrograms min/ml), the total body clearance (38.3, 42.0,
44.6 ml/min/kg), and the percentages of intravenous dose of 2-AP excreted in 24 h
as unchanged drug (0.0306, 0.0252, and 0.0492%), were independent of the dose
ranges studied. Since the amount of 2-AP excreted in 12-h bile as unchanged drug
after intravenous administration of 2-AP, 20 mg/kg, was only 0.0241 +/- 0.00156%,
and some of 2-AP excreted in gastrointestinal tract as unchanged drug was
reabsorbed, the reason for the appearance of multiple peaks after intravenous
administration of 2-AP could be at least partly due to gastrointestinal excretion
of the drug.
PMID- 9644717
TI - Bioavailability of timolol and aceclidine after ocular instillation in the
rabbit.
AB - The bioavailability of timolol and aceclidine after the ocular instillation of
each drug (timolol 0.5% or aceclidine 2%) or both combined (timolol 0.5% +
aceclidine 2%) has been evaluated in rabbits. 15 male albino rabbits were treated
by the instillation of timolol and aceclidine alone or combined in the
conjunctival sac of the right eye. Timolol concentrations in humor aqueous were
assayed at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 6 hr after instillation by high
performance liquid chromatography (HPLC). Aceclidine was assayed by a
pharmacodynamic method: pupillary diameter at the following time intervals 0
(basal value), 1 min, 5 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr after treatment. Our
results demonstrated that no differences in timolol and aceclidine
bioavailability were found between simple-drug preparations and their
combination.
PMID- 9644718
TI - Intestinal metabolism and transport of alpha-disaccharide conjugates: the role of
disaccharidase in the Na+/glucose cotransporter-mediated transport.
AB - Intestinal transport and metabolism of p-nitrophenyl alpha-disaccharides were
studied. In the absorption of p-nitrophenyl alpha-melibioside, no compounds other
than p-nitrophenyl alpha-melibioside were detected on either the mucosal or the
serosal side. In the absorption of p-nitrophenyl alpha-maltoside, on the other
hand, p-nitrophenyl alpha-glucoside was formed on the mucosal side to appear on
the serosal side. p-Nitrophenol and p-nitrophenyl beta-glucuronide also appeared
on the serosal side in the absorption of p-nitrophenyl alpha-maltoside, and the
total amount transported to the serosal side was significantly decreased in the
absence of Na+ (a cosubstrate of Na+/glucose cotransporter (SGLT1)). Furthermore,
the total transport clearance of p-nitrophenyl alpha-glucoside formed from p
nitrophenyl alpha-maltoside on the mucosal side in the p-nitrophenyl alpha
maltoside absorption, was similar to that of the absorption of p-nitrophenyl
alpha-glucoside itself. These results led to the conclusion that the intestinal
absorption of disaccharide conjugate depended on disaccharidase, and the
absorption of the alpha-maltose conjugate occurred sequentially by the maltase
catalyzed hydrolysis of the disaccharide conjugate and SGLT1-mediated transport
of the glucose conjugate.
PMID- 9644719
TI - Ameliorative effects of docosahexaenoic acid on serum lipid changes in stroke
prone spontaneously hypertensive rats.
AB - It has been shown that docosahexaenoic acid (DHA) has numerous physiological
actions. However, the precise mechanism of these actions is still obscure, and
DHA is not yet regarded as a drug. The present study was undertaken to elucidate
the effects of long-term administration of DHA on the serum lipid concentrations
in stroke-prone spontaneously hypertensive rats (SPSHR). SPSHR was selected
because serum lipid derangement is one of the primary risk factors in the
development and maintenance of hypertension. DHA-treated SPSHR showed
significantly lower blood pressure when compared with that of non-treated SPSHR;
total cholesterol, triglyceride, low density lipoprotein and lipid peroxide
levels were significantly decreased in DHA-treated SPSHR. On the other hand, the
high density lipoprotein concentrations tended to increase in DHA-treated SPSHR
when compared with those in non-treated SPSHR. These findings suggest that long
term administration of DHA has a protective effect against serum lipid
derangement in SPSHR. This DHA-induced amelioration of serum lipid changes in
SPSHR might be associated with mechanisms involving the antihypertensive action
induced by DHA.
PMID- 9644720
TI - Gastric vascular network in stroke-prone spontaneously hypertensive rats.
AB - The gastric vascular architecture in stroke-prone spontaneously hypertensive rats
(SHRSP) was studied three-dimensionally by vascular casting; controls were Wistar
Kyoto rats (WKY). The vascular network of the gastric mucosa of WKY showed a
cylindrical shape with regular morphology (honeycomb-like capillary network)
along the vascular course. In contrast, in SHRSP, an irregular vascular network
was formed, and arterioles in the gastric mucosa and serous membrane were
difficult to detect. Aneurysms were also detected in some capillaries in SHRSP.
We concluded that the development of hypertension may have caused the irregular
capillary networks in the rat stomach.
PMID- 9644721
TI - Effect of running training on brown adipose tissue activity in rats: a
reevaluation.
AB - The effect was investigated of running training on the thermogenic activity of
brown adipose tissue (BAT) in rats. The exercised rats were trained on a rodent
treadmill for 5 days per week and a total of 9 weeks. After the training, a
significantly lower rate of increase in body weight was found, suggesting some
training effect, whereas the training failed to induce a decrease in BAT mass. As
previously reported (Yamashita, Yamamoto et al., 1993), there was also a markedly
lower expression of uncoupling protein (UCP) mRNA in BAT from trained rats;
nevertheless, no definite effect of the running training was noted on either UCP
content or guanosine 5'-diphosphate binding in the mitochondria recovered from
BAT. The results obtained suggest that running training has no overt effect on
the thermogenic activity of BAT in rats.
PMID- 9644722
TI - The effect of gold on zinc in liver and in metallothionein.
AB - The question as to the increase in Zn and Cu in metallothionein (MT) in response
to gold (Au) was examined. Each rat was injected intraperitoneally once with 0.9%
NaCl or Au (5, 10 or 20 mg Au/kg b.w.). The Zn content in livers increased in
response to Au injection, while the Cu content remained unchanged. After Au
injection, 40.0-46.3% of the Au contents and 55.0-60.4% of the Zn contents in
livers were detected in cytosol, respectively. The distribution profiles of the
hepatic cytosol of Au-injected rats on a Sephadex G-75 column showed that the
amount of the increased Zn was ascribable to high molecular weight proteins and
MT. The Zn contents in the MT increased in response to Au injection. There was a
close relationship between the Zn contents in cytosol and MT. These data
demonstrated that 68% of the increased Zn in the hepatic cytosol of Au-injected
rats was bound to MT. These results suggest that the role of MT in Zn
accumulation in the liver of Au-injected rats was similar to that of MT in Zn
accumulation in liver of Zn-injected rats.
PMID- 9644723
TI - Nuclear matrix protein, tumor necrosis factor-alpha, and nitrite/nitrate levels
in patients with multiple organ dysfunction syndrome.
AB - Nuclear matrix protein (NMP), an indicator of apoptosis, was analyzed in patients
with multiple organ dysfunction syndrome (MODS). Blood levels of tumor necrosis
factor-alpha (TNF-alpha) and nitrite/nitrate (NOx) were also measured in these
patients to determine the involvement of these factors in the production of NMP.
Forty-six patients with MODS were studied, 21 (45.7%) of whom died. NMP and TNF
alpha were measured by enzyme-linked immunosorbent assay (ELISA). NOx was
measured by the Griess's method. Marshall's multiple organ dysfunction score (MOD
score) was used as an indicator of organ failure. The severity of organ failure
was assessed by use of the acute physiology and chronic health evaluation II
score (APACHE II score). The number of organs that failed was found to be
significantly correlated with the NMP level. The NMP level was also correlated
significantly with MOD score and APACHE II score, as well as with TNF-alpha and
NOx levels. NMP and NOx levels in the group that died significantly exceeded
those in the surviving group. Results suggest that apoptosis can occur in the
presence of MODS, and that its extent increases as the number of failing organs
increases. The results also suggest that TNF-alpha and NO are involved in the
induction of apoptosis.
PMID- 9644724
TI - Genistein metabolism in liver microsomes of Wistar and mutant TR(-)-rats.
AB - In mutant TR(-)-rats lack of the canalicular multispecific organic anion
transporter prevents the biliary excretion of various phase II conjugates. In
order to investigate whether this rat strain expresses high amounts of phase-I
metabolic enzymes to compensate for the deficiency an in vitro study using liver
microsomes of control and TR(-)-rats was conducted. While liver microsomes of non
mutant Wistar rats (control) have a higher total cytochrome P450 content, no
difference is found for NADPH-reductase. Expression of cytochrome P450 (CYP)
isoforms CYP1A2, 2D, and 2E1 is equal in both rat strains. CYP2B1/2 and 3A1/2,
however, are significantly impaired in livers of TR(-)-rats. The CYP dependent
metabolism of genistein (GEN), a widely used inhibitor of the tyrosinekinase, was
studied in TR(-)- and control rat liver microsomes. Three metabolites (M1-M3)
were quantified by HPLC, revealing a lower amount of M2 and M3 in TR(-)-rats.
Phenobarbital-pretreatment increased the formation of M1-M3 in both rat strains
(2-4 fold). Dexamethasone, a specific inducer of CYP 3A1/A2 in male rats caused
an even higher induction of M1-M3 (up to 20 fold) particularly in TR(-)-rats
indicating the involvement of CYP3A isozymes in genistein metabolism. Phase I
metabolism may compensate for the lack of genistein-glucuronide elimination in
TR(-)-rats.
PMID- 9644725
TI - Temperature-dependent lipid peroxidation of rat brain homogenate.
AB - When rat brain homogenate was incubated without adding iron, lipid peroxidation
occurred temperature dependently between 27 degrees C and 42 degrees C. When
homogenates of liver and heart were incubated under the same conditions, lipid
peroxidation did not occur. The brain, compared with other organs, seems to be
very vulnerable to oxidative damage with fever. Catalase promoted lipid
peroxidation. The ability of dihydrolipoic acid and alpha-tocopherol to inhibit
lipid peroxidation was very weak. In contrast, iron chelators, such as
bathophenanthroline, desferrioxamine and EDTA, strongly inhibited lipid
peroxidation, indicating that endogenous iron is involved in lipid peroxidation.
Dialysis of brain homogenate depressed the temperature-dependent lipid
peroxidation by about 30%. Then, the iron content of the homogenate decreased by
about 35%. On the other hand, dialysis of EDTA-treated homogenate completely
depressed the lipid peroxidation and the iron content of the homogenate decreased
by about 87%. Adding iron to the homogenate dialyzed after EDTA treatment
remarkably increased the lipid peroxidation, but the peroxidation reaction
proceeded temperature independently. Our results suggest that endogenous iron,
which may bind to cell components, causes temperature dependent lipid
peroxidation by a site-specific mechanism.
PMID- 9644726
TI - Nuclear pore changes and absence of apoptosis in lumbar dorsal root ganglion
neurons of doxorubicin-intoxicated rats.
AB - Doxorubicin (DXR) produces degeneration of neurons in the lumbar dorsal root
ganglion (DRG) in rats. Light microscopic studies, which included the terminal
deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
labeling method, and electron microscopic observation revealed that the moderate
nuclear and remarkable cytoplasmic degeneration of DRG neurons of Sprague-Dawley
rats after intravenous administration of 8 mg/kg of DXR was cell necrosis, not
apoptosis. In some neurons, mostly dark and usually with moderate degrees of
nuclear degenerative changes, the nuclear pores were decreased in number and
obscure 14 and 20 days after DXR administration. DXR enters presumably the
nucleus and is partly removed through the nuclear pores. However, the diameters
of nuclear pores were similar in DXR-intoxicated and control rats. The changes in
nuclear pores of neurons in DXR intoxication, which to our knowledge has not been
previously studied, are considered to be part of the degenerative or necrotic
changes of DRG neurons.
PMID- 9644727
TI - Psychological stress and educational effect during bedside practice on
psychiatric nursing.
AB - The aim of this study is to analyze the educational effect and the factors of
psychological stress of bedside practice on psychiatric nursing. The subjects
studied were 76 nursing students in a nursing college. They answered a
questionnaire and underwent the STAI-test before and after the periods of their
bedside practice during psychiatric nursing. The results obtained were as
follows; 1. The awareness structure of the nursing students was composed of 6
factors, that is, anxiety and detestation factor, understanding and acceptance
factor, social alienation factor, denial factor, affirmation factor and closed
society factor. 2. The changes in their awareness were observed before and after
the periods of bedside practice. 3. The STAI-test showed that the nursing
students frequently complained of anxiety before the bedside practice because
they had only studied about the psychoses. 4. The nursing students who had strong
anxiety also showed a deep fear and detestation. 5. Some nursing students who had
had a deep anxiety before the bedside practice found their anxiety reduced
because of the direct contact with psychotic patients. 6. Although the nursing
students had psychological stress, they were also interested in the psychiatric
nursing.
PMID- 9644728
TI - [Basic life support skills of the first aid course II/standard first aid course
ambulance personnel].
AB - This study was undertaken to evaluate thirteen elements of basic life support
skills of the First Aid Course II/Standard First Aid Course (FAC II/SFAC)
ambulance personnel and to determine the effects of FAC II/SFAC education and
basic life support instructor courses. Ninety-eight FAC II/SFAC ambulance
personnel were enrolled in this study. It was found that only half of the
personnel possessed the skills required for assessing respiration, mask holding
and producing adequate tidal volume by the bag-valve-mask devices at the
acceptable levels. Regarding the effect of the time that had passed following FAC
II/SFAC education, we did not find any correlation between the time and the
levels of skills. However, there was a tendency in which the skills for assessing
mental status/respiration and for manual airway control were less adequately
possessed by FAC II/SFAC personnel who did not take basic life support instructor
courses, particularly those who had completed FAC II/SFAC education more than
four years prior to this study. Since airway control and respiratory management
play a key role in saving patients in life-threatening conditions, we need to
critically reevaluate how the initial FAC II/SFAC education and continuing
education programs can best be implemented.
PMID- 9644729
TI - A case of pulmonary reaction with skin eruption showing a positive peripheral
lymphocyte stimulation test result for ethambutol.
AB - We report a case of an elderly male whose pulmonary reaction with skin eruption
occurred in the initial phase of chemotherapy composed of isoniazid, rifampicin,
and ethambutol (EB). A peripheral lymphocyte stimulation test (LST) showed a
positive reaction only to EB. The blood serum analysis of the patient when this
reaction occurred revealed an elevated titer of antinuclear antibody. Computed
tomography (CT) scan films of the chest when the pulmonary reaction occurred
showed multifocal subpleural consolidations. There has been only one reported
case of EB-induced pulmonary reaction and its clinical course was very similar to
ours. However, LST results and computed tomography (CT) scan findings of the
chest were not documented in that case.
PMID- 9644730
TI - [Antigen-recognition mechanism of T cells].
AB - The antigen-recognition mechanism of T cells was reviewed from the standpoint of
MHC-restriction. T cells recognize antigens presented by antigen-presenting cells
in a MHC-restricted manner. CD4+ helper T cells recognize antigens with the
context of MHC class II molecules, and CD8+ cytotoxic T cells recognize antigens
with MHC class I molecules. The MHC class I molecule is composed of alpha-chain
and beta 2-microglobulin, and MHC class II molecule is composed of alpha-chain
and beta-chain. The T cell antigen receptor is composed of alpha-chain and beta
chain, or gamma-chain and delta-chain, and CD3 complex. Antigens are processed
and presented by antigen-presenting cells to T cells in the context of MHC
molecules. Furthermore, costimulatory factors such as adhesion molecules and
cytokines are required for the full activation of T cells. The biological
significance of the T cell antigen recognition mechanism is discussed from the
standpoint of clinical application.
PMID- 9644731
TI - Physico-chemical characterization of grain dust in storage air of Bangalore.
AB - An Anderson personal cascade impactor was used to study the particle mass size
distribution in the storage air of two major grain storage centers in Bangalore.
Dust levels in storage air as well as the personal exposures of workers were
determined along with a detailed study on the particle size distribution. Protein
and carbohydrate content of the dust were also determined respectively in the
phosphate buffer saline (PBS) and water extracts by using the standard analytical
techniques. Personal exposures in both of the grain storage centers have been
found to be much above the limit prescribed by ACGIH (1995-96). But the results
of particle size analysis showed a higher particle mass distribution in the non
respirable size range. The mass median diameters (MMD) of the storage air
particulate of both the centers were found to be beyond the respirable range.
Presence of protein and carbohydrate in the storage air dust is indicative of the
existence of glyco-proteins, mostly of membrane origin.
PMID- 9644732
TI - [Research on the contents of material safety data sheets].
AB - The Material Safety Data Sheet (MSDS) system for the safe management of chemical
substances was officially promulgated in 1993 and has been gradually put into
practice through administrative guidance in Japan. However, little research has
been done on the quality of such data sheets provided from various sectors of
industries. We examined two sets of MSDSs obtained from a refractory ceramic
plant. In the first survey in 1995, the set of MSDSs was from July, 1992 to
March, 1994; and in the second survey in 1997, the set was from April, 1994 to
November, 1996. The number of MSDSs examined in these two surveys was 159 and 81,
respectively. The number of MSDSs in which "Hazard Identification" was indicated
was 100 (63%) in the 1995 survey and 75 (93%) in the 1997 survey. The number of
those in which "Toxicological Information (Stability and Reactivity)" was
indicated was 81 (51%) and 80 (99%), respectively. The description rates for the
essential items, including the above two, were found to be improving.
PMID- 9644733
TI - [Rheumatic diseases in the light of international statistic classification of
diseases and health problems (10th revision)].
PMID- 9644734
TI - [Selective inhibitors of cyclooxygenase-2: new perspectives of human diseases
management].
PMID- 9644735
TI - [Common variable immunodeficiency in adults and problems of its immunotherapy].
AB - AIM: Clinicoimmunological study of adult patients with prevailing defect of
humoral immunity, development of diagnostic criteria and treatment of this
disease. MATERIALS AND METHODS: Clinical, immunological and microbiological
examinations were made in 68 patients with defects of antibody formation.
RESULTS: Total variable immunodeficiency (TVID), selective deficiency of IgA,
congenital agammaglobulinemia, hyper-IgM-syndrome were detected in 74, 13, 10 and
3% of patients, respectively. TVID was frequently associated with respiratory,
chronic ENT and gastrointestinal diseases, low CD4+ and high CD8+ levels. The
response was achieved with combined therapy: antibacterial treatment +
immunocorrection + differentiated replacement with plasma or immunoglobulins.
CONCLUSION: In choice of immunotherapy of TVID patients it is necessary to
consider parameters of immunogram. Intravenous administration of immunoglobulin
preparations provided the highest effect in good safety.
PMID- 9644736
TI - [HLA-antigens and some pathogenetic aspects of reactive arthritis].
AB - AIM: Investigation of associations of reactive arthritis (ReA) with
histocompatibility antigens class I and II and determination of new approaches to
assessment of association ReA with antigen HLA B27. MATERIALS AND METHODS: 118
ReA patients with associated intestinal and 82 ReA patients with associated
urogenital infection were studied. The infection was identified
bacteriologically, with agglutination reaction, enzyme immunoassay, direct and
indirect immunofluorescence, culturing. HLA-antigens were studied in
lymphocytotoxic test: locus A, B and C in all the patients, DR in 65 patients.
RESULTS: ReA triggers were intracellularly parasite bacteria: facultative
parasites in the enterocolitic variant (Yersinia, as a rule), obligate parasite
in the urogenital (Chlamidia, as a rule). HLA B27 antigen was discovered in 77.5%
of patients (RR 45.8), HLA DR1--in 48.4% of patients (RR 3.3). In urogenital
variant HLA B27 antigen occurred more frequently than in enterocolitic: 87.8% (RR
95.6) versus 70.3% (RR 31.5); p < 0.01). In HLA-B27-positive patients compared to
HLA-B27-negative ones there were higher ESR (p < 0.001), leukocyte count (p <
0.05), concentrations of CRP and alpha-2-globulins (p < 0.001). CONCLUSION: In
HLA-B27-subjects optimal conditions exist for generalization of obligate
parasites and favorable for production of facultative ones. The degree of
association of ReA with HLA B27 antigens is dependent on adaptive features of
microorganisms appearing in the process of evolution--obligaty and
facultativeness of their internal parasitivity.
PMID- 9644737
TI - [Conception of direct participation of intestine in pathogenesis of rheumatoid
arthritis].
PMID- 9644738
TI - [Neopterin: laboratory marker of cellular immunity activation in rheumatoid
arthritis].
AB - AIM: Measurement of neopterin in the serum of patients with rheumatoid arthritis
(RA). MATERIALS AND METHODS: 59 patients with verified RA diagnosis (22 cases of
joint lesion stage I-IIa, 27 of stage IIb-IIIa, 10 of stage IIIb-IV established
roentgenologically, 48 patients were seropositive by IgM-rheumatoid factor) were
examined for concentrations of serum neopterin and C-reactive protein (CRP). The
activity and prognostic factors were characterized by modified Wilke method, the
severity index was calculated. 100 healthy donors served controls. RESULTS:
Immune inflammation in RA develops with growing neopterin concentration in the
serum. This concentration well correlates with inflammation activity and
intensification of systemic symptoms. CONCLUSION: Neopterin measurements may be
important for determination of inflammation activity in RA. Further efforts
should be made to ascertain relationships between neopterin hyperproduction and
disturbances of cellular immunity in RA, clinical value of neopterin assays
compared to the other laboratory evidence, feasibility of using neopterin levels
to define prognosis and efficacy of on-going therapy.
PMID- 9644739
TI - [New approaches to biological immunomodulation therapy of rheumatoid arthritis:
neutralization of basic cytokines].
AB - AIM: Investigation of efficacy of antibodies ot interferons in rheumatoid
arthritis (RA) versus relevant efficacy of the tumor necrosis factor (TNF),
comparison of the above cytokines in monotherapy and combined treatment.
MATERIALS AND METHODS: An open controlled randomized trial of clinical benefit
and tolerance of anticytokine antibodies was performed in a group of RA patients
at stage II, III and IV (1, 20 and 4 patients, respectively). The activity degree
II and III was in 10 and 15 patients, respectively. All the patients had
articular functional insufficiency of the second degree. 21 patients failed
previous therapy with basic drugs including immunodepressants. RESULTS: The
anticytokine antibodies proved to be highly effective in RA. Positive changes in
teh disease activity were achieved early after the end of the 5-day course in 88%
of patients. The most definite immediate therapeutic effect was noted in usage of
TNF antibodies both in monotherapy and in combination with other anticytokines.
Long-term effect was the best in patients given antibodies to interferon gamma.
Interferon-alpha antibodies produced weaker effect. The combined treatment had no
advantages over the monotherapy. CONCLUSION: A significant therapeutic effect of
antibodies to interferon-gamma is indicative of an important role of this
cytokine in RA pathogenesis. Anticytokine antibodies are promising as a component
of combined therapy of patients with resistant RA.
PMID- 9644740
TI - [Criteria of aggressive rheumatoid arthritis course in children].
AB - AIM: To ascertain criteria of aggressive course of juvenile rheumatoid arthritis
(JRA) during 6-12 months since the disease onset, to measure the rate of
destruction progression, to formulate indications for conduction of early
immunosuppressive therapy. MATERIALS AND METHODS: The study included 30 patients
(21 girls and 9 boys) aged 4-15 years with classic JRA. 25 children (76.2%) had
systemic, 5 children--articular disease (23.8%). RESULTS: 50% and 20% of the
examinees got the disease before they reached the age of 5 years and in puberty,
respectively. Severe systemic disease in the debute was registered in 83.3% of
patients, 16.7% developed primarily articular JRA. For 1 year the disease
transformed into generalized and polyarticular in 43.3% and 56.7% of patients,
respectively. Its activity reached the third degree in all the patients. IgG
levels exceeded the age standards 1.5 times. Articular dysfunction occurred in
100% of the cases. Destruction in the joints was recorded in 37% and 92.5% of
patients after 1 and 2 years of the disease, respectively. CONCLUSION: Early or
in prepuberty, puberty onset of JRA, systemic variants of the debute, debute by
classical seropositive RA without systemic symptoms, fast appearance of
symmetric, generalized joint lesions, recurrent course with high ESR, C-reactive
protein, IgG, growing joint functional insufficiency within the first year of the
disease may severe criteria of aggressive course of RA in children. RESULTS: The
presence of the above markers in RA patients is indication for administration of
the disease-controlling drugs within the first 12 months before development of
anatomic destruction and the patients' invalidation.
PMID- 9644741
TI - [Significance of antibodies to herpesviridae viruses detectable in rheumatic
diseases].
AB - AIM: To assay antibodies to cytomegalovirus (CMV), herpes simplex virus type 1
and 2 (HSV-1, HSV-2) and Epstein-Barr virus (EBV) in rheumatic patients and to
clarify clinical correlations. MATERIALS AND METHODS: A total of 66 patients were
examined: 7, 19, 6, 3, 5, 2 and 24 with rheumatoid arthritis (RA), systemic lupus
erythematosus (SLE), reactive arthritis (ReA), scleroderma systematica (SS),
erythema nodosum (EN), hemorrhagic vasculitis (HV), active or chronic viral
infection (A/CVI), respectively. Clinical, laboratory tests, tests for specific
IgM- and IgG-antibodies to CMV, HSV-1, HSV-2, EBV, x-ray examinations were
performed. RESULTS: IgG-antibodies to CMV were detected in 79%, VCA-IgG
antibodies to EBV in 70.3%, EA-IgG-antibodies to EBV in 56.6%, IgG-antibodies to
HSV-1 in 42.1% of patients. Active CMV infection was diagnosed in 27.8%, active
EBV infection in 56.6%, combination of CMV and EBV infection in 46.9% of cases.
High titers of antibodies to CMV and EBV correlated with such symptoms as fever,
arthritis, myalgia, carditis, hepatomegalia, migrating erythematous eruption.
Acute-phase indices were related to high titers of antibodies to CMV and EBV.
Elevated titers of antibodies to CMV and EBV were registered both in untreated
patients and in patients treated with corticosteroids, nonsteroid
antiinflammatory drugs and aminoquinoline drugs. CONCLUSION: In differential
diagnosis of rheumatic diseases it is necessary to consider possibility of CMV
and EBV infections. If these are detected, antiviral measures should be taken.
PMID- 9644742
TI - [Pathogenetic aspects of chlamydia-associated urogenic arthritis: feasibility of
microorganism reproduction in cells of articular cartilage].
AB - AIM: The study of feasibility of Chlamydia trachomatis infection and
reproduction. This microorganism is an essential etiologic factor in urogenic
arthritis, in chondrocytes and fibroblasts of human skin. MATERIALS AND METHODS:
Infection of human skin chondrocytes and fibroblasts was made with chlamydia CP-1
strain isolated from joint fluid of the patient and serially passaged in the
hen's embryo yolksacs. The inoculation results were assessed by direct staining
with the use of monoclonal and fluorescent antibodies and hematoxiline. RESULTS:
Chlamydial infection of human skin connective tissue, chondrocytes of the
auricular cartilage and fibroblasts in particular, is possible. CONCLUSION: The
findings confirm the ability of Chlamydia trachomatis to reproduce in the
cartilage tissue.
PMID- 9644743
TI - [Antibodies to low density oxidated lipoprotein and ischemic cerebrovascular
disorders in young patients].
AB - AIM: The study of the detection rate and potential pathogenetic significance of
antibodies to low density oxidated lipoprotein (LDOL) in patients who had
ischemic cerebral circulation disorder (ICCD) at young age. MATERIALS AND
METHODS: The examination (enzyme immunoassay, general and neurological
investigations, laboratory and instrumental tests) covered 148 patients who
survived ICCD at young age (mean age 37.2 years). RESULTS: 48 of 108 (44%)
patients had LDOL antibodies. Antibodies to cardiolipin, lupus anticoagulant were
recorded in 33 (31%) patients. LDOL antibodies were higher and occurred more
frequently in patients with Sneddon's syndrome (35% of patients, mean LDOL
antibodies-44 units) and primary antiphospholipid syndrome (17% of patients, 45
units) than in atherosclerotic affection of the major head arteries (4%, 29
units) or occlusion of cerebral arteries of unclear genesis (8% of patients, 29
units). CONCLUSION: ICCD were not related to fast development of cerebral
atherosclerosis or periaortitis due to production of LDOL antibodies as no
relationships were found between their rise and atherosclerotic lesions of
cerebral major arteries or periaortitis as shown by ultrasonic dopplerography or
cerebral angiography. Feasibility of LDOL antibodies participation in the
coagulation cascade and induction of hypercoagulatory condition causing ICCD
needs special investigation.
PMID- 9644744
TI - [Neurovascular syndrome in some rheumatic diseases].
AB - AIM: Assessment of neuromotor system and suprasegmentary vegetative structures in
patients with systemic vasculitis (SV), systemic lupus erythematosus (SLE),
scleroderma systematica (SS) for determination of the vegetative profile and
pathogenetic links underlying vegetative disorders. MATERIALS AND METHODS: The
examination of 125 rheumatic patients included clinical, laboratory,
instrumental, neurological, neuropsychic, electroneuromyographic, vegetologic,
pathomorphologic and biochemical investigations. RESULTS: Rheumatic patients
presented affections of the peripheral and central venous systems, vegetative
dysfunction, disturbed higher nervous activity manifesting as polyneuropathy,
mononeuropathy, pyramid syndrome, dystonia, hypothalamic syndrome, reduced
adaptive ability, low tonicity of the sympathetic nervous system, terminal
branches of the motor axons, etc. CONCLUSION: Therapy of nervous disorders in
rheumatic patients comprises treatment of cerebral circulation (vascular,
nootropic drugs, cerebrolysin), asthenic, neurotic and vegetative disorders
(sedative and vegetotropic drugs, etimisol, adaptogens), abnormalities of
peripheral nervous system (amiridin, anticholinesterase preparations, vitamins B
and others). Follow-up and correction of the on-going therapy contribute to a
decrease in the number of invalidating and lethal neurological complications.
PMID- 9644745
TI - [Clinical and laboratory characteristics of patients with Sjogren's disease
lasting from young age].
AB - AIM: Characterization of Sjogren's disease (SD) with onset at early age basing on
the comparison of two patient groups--with the disease onset at the age under 30
and over 50. MATERIALS AND METHODS: Clinical, ophthalmological and stomatological
examinations were performed in 31 SD patients who developed the disease at the
age under 30 (group 1) and over 50 (group 2). RESULTS: In group 1 the disease
started with parotitis in 42.8% of cases, dysfunction of secreting epithelial
glands was rare, functional activity of exocrine glands was normal,
dysproteinemia (high total protein levels, hypergammaglobulinemia,
hypoalbuminemia) and immunological defects (high levels of circulating immune
complexes, rheumatoid factor, antinuclear factor) were more pronounced. At
retrospective analysis not only a decline of functional activity of the salivary
and lacrimal glands but also appearance of systemic symptoms were registered.
CONCLUSION: Development of systemic SD symptoms at young age necessitates early
pathogenetic therapy employing corticosteroid, cytostatic and other drugs.
PMID- 9644746
TI - [Madecassol treatment of systemic and localized scleroderma].
AB - AIM: The trial of efficacy of 6-month therapy with madecassol (tablets, ointment,
powder) of patients with systemic and focal scleroderma (SS and FS). MATERIALS
AND METHODS: 54 patients (49 females and 5 males) aged 15 to 70 years with
scleroderma running from 3 months to 15 years entered the study. 30 patients had
typical SS, 24 patients had FS. Tablets were given to 18 patients, ointment was
applied in 42 patients, powder in 3 and tablets + ointment in 9 patients.
Madecassol 10 mg tablets were taken 3 times a day by patients with SS and
advanced FS. The ointment was preferred in ulcers and scars on fingers and toes
in SS and vascular trophic lesions in FS. In active focal scleroderma the
ointment was applied to the skin lesions. The ointment was used 2 times a day (in
the morning and evening) for 1-6 months. Madecassol powder was employed rarely,
primarily of anal and vulval lesions. RESULTS: 6-month oral course (30 mg/day) in
12 SS patients brought about a decrease of indurative lesions, hyperpigmentation
(8), vascular trophic disorders (6) and improvement of general condition (5).
Subjective response was good in 10 patients and corresponded to absence of
progression. In progressive disease and diffuse skin lesions the drug was
ineffective. The best response was obtained in local application of madecassol
ointment on digital ulcers in SS. CONCLUSION: Madecassol is effective and well
tolerated and therefore recommended for oral and local use in combined treatment
of SS adn FS. Indications for per os utelization are: chronic or subchronic SS
with limited skin involvement, advanced and/or prone to progression FS in which
combined administration of the tablets and ointment is proposed.
PMID- 9644747
TI - [Outpatient care of young invalids with locomotor defects].
AB - AIM: The study of somatic health in patients with locomotor defects (infantile
cerebral paralysis, meningoencephalocele, myodystrophy) to reveal abnormalities
in function of the principal systems and organs of these patients. MATERIALS AND
METHODS: The examination covered 93 students of Moscow institute for invalids
suffering from locomotor defects (mean age 18.2 +/- 0.1 years). Clinical,
laboratory, instrumental tests, ultrasound investigation of the viscera and
heart, gynecological functional tests were made. RESULTS: Defects were found
almost in all the essential systems of the body in the majority of the invalids.
The changes revealed were both functional and organic. Relevant correction was
needed. Affection of the somatic organs impaired adaptation, resulted in still
worse conditions for learning. Attendant somatic diseases aggravated the
underlying disease. CONCLUSION: Visceral affections in patients with locomotor
defects aggravate the underlying disease and provoke more severe disability. Poor
rehabilitation results lead to defective social adaptation. The authors propose
introduction of special therapeutic programs for primary and secondary
prophylaxis of somatic lesions in invalids with locomotor affections. Further
study of somatic status of invalids is thought valid.
PMID- 9644748
TI - [Cerebral pathology in inactive rheumatism].
AB - AIM: Characterization of cerebral pathology in inactive phase of rheumatism.
MATERIALS AND METHODS: Clinical, experimental psychological examinations were
performed in 110 rheumatic patients with inactive disease. Computer tomography of
the head was carried out in 45 patients. RESULTS: Psychic defects were absent
only in 2.73% of the examinees. The rest had different neurotic symptoms manifest
as panic attacks (> 50% of cases) or mildpsychoorganic shifts (60.91% of cases).
Computer tomography of the brain has revealed hypodensive foci, deformed
subarachnoid spaces and cerebral ventricles, hydrocephalia in 66.67% of the
patients. These occurred more frequently in patients with psychoorganic syndrome
or valvular heart diseases. CONCLUSION: Treatment and rehabilitation of rheumatic
patients should also include measures to correct psychic and cerebral
abnormalities frequently present in such patients.
PMID- 9644749
TI - [Changes of lipid metabolism in cardiac failure patients with rheumatic heart
disease].
AB - AIM: The study of lipid metabolism parameters involved in lipid mechanisms of
damage and elucidation of their role in disorders of central hemodynamics (CH),
microcirculation (MC) and oxygenation (OG) of peripheral tissues in cardiac
failures (CF) in rheumatic patients. MATERIALS AND METHODS: In 55 patients with
rheumatic heart disease (RHD) with CF measurements were made of serum
characteristics of peroxidation-antioxidant balance, activity of phospholipase
A2, concentration of nonesterifized fatty acids, total lipids, total
phospholipids, total, ether-bound and free cholesterol, skin OG and MC.
Tetrapolar chest rheography was followed by calculation CH parameters. RESULTS:
CF aggravation occurred in parallel with progression of generalized activation of
lipid peroxidation (LPO) and phospholipase A2. LPO activation contributes to
inhibition of antioxidant activity and to decline of hypercholetsrolemia.
Negative correlation exists between primary LPO products, dienic conjugates and
CH. CONCLUSION: LPO and phospholipase A2 activation are essential in the onset
and progression of CF in RHD patients. This should be considered in therapy of
such patients.
PMID- 9644750
TI - [Comparative efficacy, safety, cardio-hemodynamic effects of isosorbide dinitrate
(ID) aerosol and sublingual tablets of nitroglycerin].
AB - AIM: To study efficacy, safety, cardiohemodynamic effects of ID aerosol--isoket-
for relief of anginal attacks and their prevention in long-term treatment.
MATERIALS AND METHODS: 15 patients with ischemic heart disease suffering from
stable angina class II-III. Isoket was tried for efficacy, tolerance, hemodynamic
parameters, morphofunctional status of the heart, exercise tolerance. RESULTS:
Isoket aerosol in a dose 1.25 mg as a single oral spray arrested anginal attacks
in all the patients. In long-term regimens good antianginal effect was achieved
in 60% of cases. The ID aerosol produces a fast antianginal effect, improves
morphofunctional cardiac parameters and exercise tolerance. CONCLUSION: Isoket
spray is effective and safe antianginal drug.
PMID- 9644751
TI - [Comparative trial of 3-day azithromycin versus 10-day coamoxilav course efficacy
in acute sinusitis].
AB - AIM: To investigate the validity of a short-term course of azitromycin in acute
sinusitis (AS). Comparison of clinical and bacteriological effects, tolerance of
azitromycin and co-amoxiclav. MATERIALS AND METHODS: 50 AS patients were given a
single 500 mg daily dose of axitromycin for 3 days and 50 such patients received
co-amoxiclav 625 mg 3 times a day for 10 days. The examination performed before
the treatment, 72 hours, 10-12 and 26-30 days after its beginning assessed the
presence of fever, head ache, pain at palpation at the site of the sinuses
projection, nasal breathing and discharge. X-ray examination and microbiological
analysis of the puncture biopsy from the nasal sinuses were conducted before
treatment and on its day 10-12. RESULTS: On the treatment hour 72 and day 10-12
azitromycin efficiency was significantly higher than that of co-amoxiclav.
Recovery on the treatment day 10-12 was registered in 41(82%) and 26(52%)
patients, improvement--in 6(12%) and 21(42%), no effect--in 3(6%) and 2(4%)
patients, respectively, for azitromycin and co-amoxiklav. On the treatment days
26-30, 45 and 43 patients recovered, respectively. The causative agents were
mainly S.aureus and Str.pyogenes. Eradication of the pathogens in response to
azitromycin occurred in 29, to co-amoxiclav in 18 patients. The latter caused
side effects more frequently. CONCLUSION: Azitromycin vs. co-amoxiclav provides
cure in acute sinusitis for a shorter time, is better tolerated and less toxic.
PMID- 9644752
TI - [Antibacterial therapy in rheumatology. Current problem status].
PMID- 9644753
TI - [Wide-field capillaroscopy in diagnosis and differential diagnosis of rheumatic
diseases].
PMID- 9644754
TI - [Therapeutic principles in systemic lupus erythematosis with phospholipid
syndrome].
PMID- 9644755
TI - [Ataxia and paralysis in meat chickens, as a result of an infection with avian
encephalomyelitis virus in the breeding flock].
AB - An outbreak of avian encephalomyelitis (AE) in 7 broiler flocks, with signs of
ataxia and paralysis is reported. The diagnosis was made by immunofluorescence,
histopathology and virus isolation. The breeding flock had a temporary drop in
egg production and reduced hatchability caused by late embryonic mortality. The
breeding flock had not been vaccinated against AE. The problems were probably
caused by vertical transmission of AE virus.
PMID- 9644756
TI - [Risk factors for Salmonella dublin infections on dairy farms].
AB - A case-control investigation of the risk factors for Salmonella dublin infections
on 126 dairy farms identified the following variables as being significantly
associated with infection: standardized farm size and presence of water courses.
Contrary to expectations, contact with cattle from other farms when the animals
were turned out to grass was negatively associated with S. dublin infection. The
purchase of cattle from other farms was a risk factor. There were more infections
when feed consisted of grass alone than when grass was supplemented with maize or
grass silage. S. dublin infections were strongly correlated with liver fluke
infections.
PMID- 9644757
TI - [Food panel and diet for domestic animals].
PMID- 9644758
TI - [Splicing factors in oocyte nuclei from human antral follicles].
AB - Three groups of oocytes in the human antral follicules were previously
distinguished on the basis of nuclear structures arrangement and 3H-uridine
incorporation in the oocyte nuclei revealed by ultrastructural and
autoradiographic research (Parfenov et al., 1984, 1989). These groups can be
regarded as consecutive states of oocyte development, i. e. active, intermediate
and inactive ones. The latter is characterized by compactization of nuclear
structures arranged within a limited nuclear volume. The present study concerns
the distribution of splicing factors (snRNP and SC35) and p80 coilin in the
nuclei of oocytes being at either of the three states. Along with transcription
decreasing in oocyte nuclei, reduction of snRNP and SC35 amounts in the
karyoplasm was detected. Simultaneously, accumulation of these splicing factors
occurred in clusters of interchromatin granules (CIG). snRNP and SC35 are
spatially segregated in CIG. snRNP are located within the fibrillar zones of CIG,
while SC35 corresponds to the granular component of CIG. CIG are the only
structures containing splicing factors in the nuclei of oocytes from the human
antral follicules. These nuclei lack typical coiled bodies (CB). Considerable
amounts of the marker protein of CB--p80 coilin are revealed in the nucleolus
like bodies (NLB) of human oocyte nuclei. Contrary to the data obtained on the
oocytes from the antral follicules of other mammals (Kopecny et al., 1996a,
1996b) NLB in human oocytes do not contain snRNPs and SC35. The present study
allows to make the following conclusions: a) splicing factors recruted to the
sites of transcription in karyoplasm of oocytes are assembled in CIG when
inactivation of transcription takes place; b) CIG in preovulated human oocytes
play substantial role in the storage and preservation of splicing factors.
PMID- 9644759
TI - [Nucleolar apparatus of neurosecretory cells in the hypothalamus of rats of
different age during acute immobilization stress].
AB - To determine condition and adaptive capacity of cell nucleoli at ageing, the
effect of acute immobilization on the hypothalamic neurosecretory cells was
investigated in young and old male Wistar rats. Using immunohistochemical methods
and nucleolometry we have shown that: 1) the nuclear volume in all neurosecretory
cells is increased; 2) the share of cells, containing nucleoli with marginal
position or multiple nucleoli in the nuclei, displays opposite changes in young
and in old rats under stress condition. We suppose that adaptive mechanisms are
different in young and old animals. Although, both kinds of morphological
reorganization result in the increase in functional activity.
PMID- 9644760
TI - [Changes in the structure of the nucleus of neocortical neurons during deficiency
of serotonin and catecholamines].
AB - The study was taken on Wistar rats using selective neurotoxins 5,7
dihydroxytriptamine and 6-hydroxydopamine. The reaction of neocortical neurons to
monoamine depletion was examined. Alterations in chromatin distribution and
partial nucleolar segregation were detected in cell nuclei of some neurons.
Peculiar intranuclear inclusions, persisting for a long period, are also found
out. We propose that detected changes in the nuclear structure are due to
intracellular adaptive reactions associated with alterations in nuclear
cytoplasmic transport and protein synthesis.
PMID- 9644761
TI - [The effect of calcium precipitate of double-stranded RNA on erythropoiesis in
rats with acute anemia].
AB - On the model of experimental acute anaemia of rats, induced by injection of
phenilhydrazine, the influence of calcium precipitate of double-stranded RNA (Ca
ds-RNA), introduced during the crise of anaemia, on the process of erythron
restoration, was studied. In the presence of Ca-ds-RNA the number of pro- and
erythroblasts in fission increases by 1.5 times, compared with "pure" anaemia
situation, and accordingly there is a marked decrease in the share of microcytes,
which play an important role in the restoration of cell number, and in the
erythron recovery after the crise of anaemia. Less pronounced is the influence of
Ca-ds-RNA on the macrocytosis, which keeps its value in spite of the increase in
the speed of development and of the number of normocytes after Ca-ds-RNA
introduction. The mechanism of Ca-ds-RNA inclusion in the system, which controls
the process of erythropoiesis during anaemia, is discussed. A conclusion is drawn
that Ca-ds-RNA may directly affect the inductive stage of erythropoiesis,
stimulating the formation of competent erythroid cells in population of stem
haemopoiethic cells and their proliferation. Further development of bone marrow
cells takes place according to the known programme of erythropoiesis whose
variations are stimulated by the current conditions of its realization, but not
by the presence of Ca-ds-RNA.
PMID- 9644762
TI - [Spontaneous reversion of tumor cells as a source of dormant metastases].
AB - In the present paper we have shown that JB6 and PDV murine skin carcinoma cells,
as well as previously described sarcoma B6-4 cells, can revert to a nontumor
phenotype. Revertant carcinoma clones could not grow in soft agar conditions and
like sarcoma revertants acquired dependence on peptide growth factors, and
exhibited a reduced expression of c-jun. Spontaneous revertants were shown to be
instable. They could revert back to a transformed phenotype in 1-5 months of in
vitro passaging. Being inoculated in syngeneic animals, these transformed cells
show a recurrence in 2-5 months, similar to that of a dormant metastasis. Thus,
dormant revertant cells are believed to be included in many tumors of different
origin. So, spontaneous reversions of tumor cells may play an important role in
the dormant metastatic process. The cause of these frequent spontaneous transient
reversions and revertant instability appears to be of epigenetic nature. Causes
and mechanisms of cell transformations and reversions remain to be clarified.
PMID- 9644763
TI - [Expression of intermediate filament proteins in MDCK cells cultured in the three
dimensional gel in the presence of cytokine HGF/SF].
AB - An immunomorphologic study was made of expression of intermediate filament
proteins--keratin and vimentin--in the structures formed in branching
tubulogenesis of Madin-Darby Canine Kidney epithelial cells (MDCK, clone 20),
cultured in three-dimensional collagen gel in the presence of the "scatter
factor" (HGF/SF). An improved method of parallel immunostaining of the whole
branching structures and of their cryostat cross-sections was used. It was shown
that both the discoid epithelial cells, forming walls of tubules with inner clear
spaces, and the fibroblast-like cells invading the collagenic gel coexpressed
keratin and vimentin. Thus, in the studied system of simplified morphogenesis in
vitro, some conservatism of intermediate filament protein expression was revealed
which does not respond to changes in cell shape or cell localization.
PMID- 9644764
TI - [Activity of various energy metabolism enzymes in the rat placenta after
treatment with acetone].
AB - In the rat placenta symplastotrophoblast the activity of glucose-6-phosphatase
increased and that of Mg-adenosine-thriphosphatase and succinate dehydrogenase
decreased under the influence of joint and separate action of acetone vapour and
high air humidity. The activity of alkaline phosphatase is oppressed only at high
humidity or in combination of high humidity and acetone.
PMID- 9644765
TI - [Karyotypic instability of peripheral blood lymphocytes in cows Bos taurus L.
infected with bovine leukemia virus].
AB - Chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs), aneuploidy and
proliferative potential (PP) were investigated in peripheral blood lymphocytes of
healthy cows (control group-C), BLV-(bovine leucosis virus)-infected cattle
without hematological abnormalities (RID--seropositive group (I) and affected
with leucaemia (lymphocytosis (LC), lymphoma (L)). Nonrandom chromosomal (marker)
aberrations were not found in the cow group at stage LC. The levels of aneuploidy
and SCEs increased in the cow group at stage L compared to the cow group at stage
I. Polyploidy: C--1.9 +/- 0.28, I--3.5 +/- 0.22, LC--6.1 +/- 0.82, L--10.5 +/-
0.51 (P < 0.01). Hypoploidy (2n = 58): C--3.0 +/- 0.17, I--54 +/- 0.71, LC--12.1
+/- 0.72, L--14.0 +/- 0.65 (P < 0.01). SCEs: C--3.8 +/- 0.26, I--5.4 +/- 0.15, LC
-7.2 +/- 0.16, L--9.7 +/- 0.26 (P < 0.01). There are no differences in CAs rates
and PP between groups of cows at all the observed stages of leucaemic process.
The obtained results are discussed in terms of cytogenetic aspects of leucaemic
process in cows.
PMID- 9644766
TI - [Stabilization by visible light of macromolecular chromatin complexes in the
presence of ethidium bromide].
AB - A method of induction of multiple DNA-protein and protein-protein cross-links in
chromatin of isolated nuclei has been developed. The cross-linking is brought
about by mutual effect of fluorochrome ethidium bromide (EtBr) and irradiation
with blue light. Electron microscopic analysis of nuclei isolated in solutions
with various concentrations of divalent cations, stained with EtBr and irradiated
with blue light, has demonstrated that the method leads to a selective
stabilization of macromolecular complexes of chromatin against various treatments
causing decompactization of native chromatin. Besides that, the stabilization of
nucleoli and clusters of interchromatin granules takes place. On the other hand,
the same treatment does not stabilize elementary chromatin fibers (about 30 nm
thick), and the transition to the nucleosomal fiber occurs after extraction of
histone H1 with 0.6 M NaCl. Electrophoretic analysis of proteins from control and
irradiated nuclei shows the basic role of non-histone proteins in the
stabilization. The data are discussed based on the assumption on the availability
of some "intermediate" levels of chromatin compaction between 30 nm chromatin
fiber and mitotic chromosome.
PMID- 9644767
TI - Ultrasonographer's wrist--an occupational hazard.
PMID- 9644768
TI - Microcephaly--no small deal.
AB - Anatomic shortening of the fetal frontal lobe seems to precede microcephaly.
Brain size determines the size of the calvarium. The report by Pilu and
colleagues provides a physiological basis for recent anatomical observations made
regarding microcephaly. Biometry of the frontal lobe of the fetal brain may be a
valuable tool for the identification of the fetus at risk for microcephaly. A
thorough investigation of the subtle brain anatomy of the developing fetus is
necessary in suspicious cases. Prenatal studies have suggested that abnormalities
of neurocranial architecture occur in approximately two-thirds of cases. Steinlin
and colleagues found a much higher incidence in children (90%) affected by
microcephaly. Either the progressive nature of the condition or the improved
sensitivity of childhood magnetic resonance imaging (used in their study) over
prenatal ultrasonography for the detection of subtle brain abnormalities may
account for this difference. However, high-resolution ultrasonographic
instruments should allow for the detection of many accompanying neuroanatomic
abnormalities, possibly before the markedly small calvarium is seen. Finally,
Pilu and colleagues have shown that the underlying conditions that may predispose
to brain atrophy may be recognizable with Doppler ultrasonography.
PMID- 9644770
TI - Inter-twin membrane folding in monochorionic pregnancies.
AB - This study examines the value of assessing inter-twin membrane folding in
monochorionic twin pregnancies in the prediction of twin-to-twin transfusion
syndrome. In 83 monochorionic twin pregnancies ultrasound scans were carried out
at 10-14, 15-17 and 19-21 weeks to investigate folding of the inter-twin membrane
as an early sonographic feature of inter-twin discrepancy in amniotic fluid
volume. There were 23 (28%) cases of membrane folding, which was first observed
in one case at 10-14 weeks, in 21 cases at 15-17 weeks and in another case at 24
weeks. In 12 (52%) of the 23 cases the pregnancy progressed to severe twin-to
twin transfusion syndrome and 10 of these were treated by endoscopic laser
coagulation of the placental vascular anastomoses. In the other 11 cases there
was a moderate syndrome with large discrepancies in amniotic fluid volume and
fetal size, persisting throughout pregnancy. In the severe group, five
pregnancies resulted in live birth of both babies, three in live birth of one and
intrauterine death of the other twin and in four cases there were no survivors.
In the moderate group, all babies survived and the inter-twin disparity in birth
weight was more than 20%. Similarly, all 60 pregnancies with no membrane folding
resulted in live births. In all three groups there was an increase in inter-twin
disparity in fetal size with gestation and the greatest inter-twin disparities
were in those with moderate twin-to-twin transfusion syndrome from as early as
the 10-14 week scan. These findings demonstrate that folding of the inter-twin
membrane occurs in about one-quarter of monochorionic twins and in about half of
these there is subsequent development of severe twin-to-twin transfusion
syndrome.
PMID- 9644769
TI - Prenatal diagnosis and outcome of subamniotic hematomas.
AB - Subamniotic hematomas are classical placental pathological lesions resulting from
the rupture of chorionic vessels near the cord insertion. Most subamniotic
hematomas are found after birth and result from excessive traction on the
umbilical cord at delivery. The development of these lesions has been rarely
reported in utero. We report here five cases of subamniotic hematomas diagnosed
by ultrasound between 18 and 30 weeks of gestation. The sonographic features were
those of a poorly reflective oval-shaped cystic mass overlying the fetal plate of
the placenta and covered in a thin membrane. In all the cases, a cystic structure
containing a thrombotic mass arising from the amniotic membrane, which was
attached to the fetal placental surface, was found after delivery. A high
maternal serum alpha-fetoprotein level was found retrospectively in the four
cases for which this information was available. Two pregnancies were complicated
by slow fetal growth, one by vaginal bleeding and one by polyhydramnios. These
findings demonstrated that subamniotic hematoma can be accurately diagnosed in
utero by ultrasound and differentiated from other lesions of the placental
chorionic plate. The findings also show that, although the lesion is located
between the chorion and the amnion, it can be associated with fetomaternal
hemorrhage and with fetal growth restriction.
PMID- 9644771
TI - Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies with
small-for-gestational-age infants.
AB - Our purpose was to evaluate whether the maternal ophthalmic artery pulsatility
index in normotensive pregnancies with small-for-gestational-age (SGA) fetuses is
different from that in normotensive pregnancies with appropriate-for-gestational
age (AGA) fetuses. The cross-sectional study involved a group of normotensive
pregnant women at > 34 weeks' gestation; 16 had fetuses that were AGA and 13 had
fetuses that were SGA. Color and pulsed Doppler ultrasonography was performed in
the ophthalmic arteries in each case and the pulsatility index and mean velocity
were calculated. The heart rate and mean arterial blood pressure were also
recorded. The pulsatility index of the ophthalmic artery (2.04 +/- 0.39) in
normotensive pregnant women with SGA fetuses was significantly lower than that
(2.87 +/- 0.64) in normotensive pregnant women with AGA fetuses (p < 0.05). The
mean velocity (15.0 +/- 2.7 cm/s) in the women with SGA fetuses was significantly
higher than that (10.2 +/- 2.7 cm/s) in the women with AGA fetuses (p < 0.05).
There was no significant difference in maternal heart rate or mean arterial blood
pressure between the groups. These results suggest that vascular resistance in
the maternal orbital circulation is reduced in pregnancies that are normotensive
but which are associated with SGA fetuses.
PMID- 9644772
TI - Ultrasonographic patterns of polycystic ovaries: color Doppler and hormonal
correlations.
AB - Ultrasound has been used in the identification of two different morphological
patterns of polycystic ovaries, namely a peripheral cystic pattern and a general
cystic pattern. The aim of this study was to evaluate whether patients with the
peripheral form of polycystic ovaries showed different ovarian and uterine blood
flow from those with the general form, and to investigate whether there was a
correlation between the forms and different hormonal parameters. Eighteen
patients with the general form and 16 patients with the peripheral form of
polycystic ovary underwent clinical, biochemical, gray-scale and color Doppler
ultrasonographic evaluation. The parameters analyzed confirmed polycystic ovarian
syndrome (PCOS) in all patients. Individual levels of plasma luteinizing hormone
(LH), follicle stimulating hormone (FSH), testosterone, androstenedione and
estradiol did not differ between the groups. However, there was a significantly
higher LH/FSH ratio and a greater stromal echodensity in the peripheral cystic
group than in the general cystic group. Doppler ultrasonography demonstrated
significantly lower pulsatility index values in the intraovarian arteries of the
peripheral cystic group and a higher rate of visualization of these arteries than
in the general cystic group. These findings suggest that, apart from the LH/FSH
ratio, the different morphological types of polycystic ovary do not reflect
differences in endocrine profile. The differences in blood flow demonstrated by
Doppler assessment in each case, however, showed that PCOS does not predetermine
a single intraovarian blood flow pattern.
PMID- 9644773
TI - An evaluation of sonohysterography and diagnostic hysteroscopy for the assessment
of intrauterine pathology.
AB - The availability of advanced hysteroscopic surgical techniques has changed the
management of abnormal uterine bleeding. The aim of this study was to evaluate
the use of transvaginal sonography (TVS), sonohysterography (SH) and diagnostic
hysteroscopy (DH) for the preoperative assessment of the uterine cavity. The plan
was to investigate 100 patients with abnormal uterine bleeding despite
conventional medical treatment. The endpoints were uterine abnormalities detected
by operative hysteroscopy and histology, and subjective estimates of discomfort
during TVS and SH. A total of 104 patients (aged 26-79 years) were recruited and
98 (94%) underwent all three diagnostic procedures. Uterine abnormalities were
present in 52 patients (53%). There were 25 cases with at least one endometrial
polyp, 17 with submucous fibroids, seven with endometrial hyperplasia and three
with an adenocarcinoma. The overall sensitivity of TVS improved after SH from 67
to 87% and the specificity from 89 to 91%. The positive predictive value
increased from 88 to 92% and the negative predictive value from 71 to 86%. The
use of SH also improved the quality of information about the location and size of
polyps and submucous fibroids. Increased endometrial thickness associated with
adenocarcinoma was detected in all cases (three of three) by TVS and in four of
seven cases of hyperplasia (five of seven cases after SH). Most patients reported
minor discomfort during TVS or SH and no side-effects were apparent. The
sensitivity of DH was 90% (92% for polyps, 88% for fibroids); two cases with a
polyp, two with a submucous fibroid and one with endometrial hyperplasia were not
detected. The use of saline infusion to enhance visualization of the endometrium
increases the diagnostic accuracy of transvaginal sonography to approach that of
diagnostic hysteroscopy and also provides some additional information. This
development has implications for the management of uterine bleeding disorders.
PMID- 9644774
TI - Ultrasonographic measurement of endometrial thickness during hormonal replacement
therapy in postmenopausal women.
AB - The objective of this study was to measure endometrial thickness by transvaginal
ultrasonography during two regimens of hormonal replacement therapy (HRT) in
postmenopausal women and to compare these data with endometrial histology.
Transvaginal ultrasonographic evaluation of endometrial thickness and endometrial
biopsy were performed in 80 postmenopausal women before and after 6 months of HRT
(between the 24th and the 28th day of the cycle). The group was randomized so
that 40 women (Group A) were treated with a continuous sequential regimen
consisting of 5 micrograms/day of estradiol continuously and 5 mg/day of
medrogestone from the 17th to the 28th day of the cycle; and 40 women (Group B)
were given continuous administration of 50 micrograms/day estradiol and 5 mg/day
medrogestone. Prior to therapy, there was no significant difference in mean
endometrial thickness between the groups. After 6 months of therapy, endometrial
thickness was significantly increased in comparison with basal values in both
groups. The mean value was significantly higher (p < 0.001) in Group A (8.5 +/-
3.7 mm) than in Group B (3.6 +/- 1.3 mm). In Group A, endometrial thickness was <
or = 4 mm in 16.7% of patients and < or = 8 mm in 69.5% of patients. In Group B,
91% of patients had an endometrium of < or = 4 mm. In both groups, the thickness
of the atrophic endometrium was less than that of the other histological types of
endometrium (4.1 +/- 0.3 mm for Group A and 3.5 +/- 1.2 mm for Group B). In Group
A, the difference in mean endometrial thickness between the proliferative and
secretory endometrium was not statistically significant. In both groups, the
transvaginal ultrasonographic measurement of endometrial thickness of < or = 4 mm
had a high sensitivity for detecting atrophic endometrium (83.3% for Group A and
93.7% for Group B).
PMID- 9644775
TI - Alternative technique for Nd: YAG laser coagulation in twin-to-twin transfusion
syndrome with anterior placenta.
AB - Nd: YAG laser coagulation is used to treat severe twin-to-twin transfusion
syndrome (TTS). Success of the technique depends on visualization of the
placenta, the fetal membranes and the targeted vessels, as well as obtaining an
optimal inclination angle for laser coagulation. In the rare case of an extensive
anterior placenta, it may be difficult to achieve these conditions using the
percutaneous approach. Here, we propose an alternative to the percutaneous
procedure. Modifications involve an open access and the use of a flexible cannula
and bent scope. An extraplacental area, usually at the fundus, is identified by B
mode and color Doppler imaging. A mini-laparotomy is made under general
anesthesia. The viscera are retracted and the cannula is inserted under direct
view and ultrasound control by the Seldinger technique. The curved fiberscope is
passed through the flexible cannula, allowing adequate inspection of the
placenta, and target vessels can be coagulated at an angle close to 90 degrees.
After the procedure, the uterus is closed primarily to prevent postoperative
leakage of amniotic fluid or hemorrhage. This technique has been successfully
used in six patients with TTS and a completely anterior placenta, with a
gestational age between 18.5 and 22.0 weeks. In all patients, the amniotic cavity
was accessed without hemorrhage. The outcomes are similar to those published
previously for laser coagulation. The mean interval from intervention until
delivery was 10.5 weeks. All 12 fetuses were live born but four died from
complications of extreme prematurity. No maternal complications occurred.
PMID- 9644776
TI - The instantaneous measurement of multiple Doppler spectra in the investigation of
ovarian masses.
AB - The use of Doppler indices of tumor vascularity as markers for malignancy has
been a subject of debate, with inconsistencies in specificity and sensitivity as
well as in the diagnostic cut-off values. Part of the discrepancy might be
explained by the limited number of vessels selected within the tumor for Doppler
evaluation. A typical sample of three or four vessels may not be sufficiently
large for correct representation of the vasculature of the tumor, which may
contain many vessels. The existing conventional Doppler (color and spectral)
techniques clearly have limitations. We present here a novel Doppler modality,
namely two-dimensional spectral Doppler imaging (SDI), which allows the
acquisition of many Doppler spectra within a few seconds. The operator selects a
region of interest within a color Doppler image. The Doppler sequence is
initiated and the entire selected region is automatically scanned for about 20 s
until all spectral Doppler data have been acquired and processed. The system
computer generates a color-coded map of the desired Doppler indices overlaid on
the gray-scale image. The system also displays a cumulative histogram or a table
of the requested Doppler index from all the sections in the tissue. The whole
process is automatically performed by the system computer, without any need for
operator intervention. The system provides the examiner with a 'fishing net' for
Doppler indices, instead of the 'fishing hook' used in current techniques.
PMID- 9644777
TI - Prenatal diagnosis of microcephaly assisted by vaginal sonography and power
Doppler.
AB - In two mid-trimester fetuses with microcephaly, transvaginal sonography revealed
aberrant findings, including large subarachnoid spaces and a rudimentary shape of
the lateral ventricles. In one of these fetuses, power Doppler ultrasound
demonstrated a discrepancy in the size of the signals generated by the
intracranial arteries branching from the internal carotids and those branching
from the vertebral arteries, and this was interpreted as the consequence of a
reduced blood supply to the undersized cerebral hemispheres. We suggest that
evaluation of intracranial anatomy by transvaginal sonography and power Doppler
examination of the cerebral vessels may be of value in the diagnosis of fetal
microcephaly.
PMID- 9644778
TI - Prenatal diagnosis of otocephaly using two-dimensional and three-dimensional
ultrasonography.
AB - We report a case of the prenatal diagnosis of a very rare anomaly, namely
isolated otocephaly, using two-dimensional and three-dimensional ultrasound at 24
weeks of gestation. Two-dimensional ultrasound revealed polyhydramnios, absence
of a stomach shadow, hypotelorism and a proboscis-like mass. Three-dimensional
ultrasound gave a precise demonstration of the striking craniofacial features of
otocephaly including agnathia, synotia, microstomia and protuberance of the nose
mouth fusion. The use of three-dimensional ultrasound provided a whole view of
the very rare lethal malformation in utero and contributed significantly to
prenatal diagnosis.
PMID- 9644779
TI - Prenatal ultrasound diagnosis of massive subchorionic thrombohematoma.
AB - Massive subchorionic thrombohematoma is a rare condition in which a large
maternal blood clot separates the chorionic plate from the villous chorion. This
condition is usually complicated by intrauterine growth restriction, and is often
associated with fetal distress and perinatal death. We present a case in which
the diagnosis of massive subchorionic thrombohematoma was made at 24 weeks'
gestation. Doppler ultrasound helped to confirm the diagnosis and demonstrated
severely abnormal umbilical blood flow. Two days after the diagnosis, fetal
distress prompted emergency Cesarean delivery of a growth-restricted infant.
PMID- 9644780
TI - Ultrasound diagnosis and follow-up of gestational trophoblastic disease.
PMID- 9644781
TI - Endometrial pathology in hypertensive women.
PMID- 9644782
TI - A critical review of penile revascularization procedures.
PMID- 9644783
TI - Prognostic significance of p53 protein overexpression in transitional cell
carcinoma of the renal pelvis and ureter.
AB - Fifty-three patients with invasive transitional cell carcinoma of the renal
pelvis and ureter were studied for p53 protein overexpression by
immunohistochemistry. Overexpression of p53 protein was observed in 19 patients
(35.8%). There was a significant correlation between overexpression of p53
protein and histologic grade (p < 0.01). However, there was no correlation found
between p53 immunoreactivity and pathologic stage. By univariate survival
analysis, a significant difference in cumulative survival was observed between
stage pT2 and stage pT3 or pT4 tumors (p < 0.05). The difference in survival
between patients with p53-positive and negative tumors did not reach statistical
significance (0.05 < p < 0.01). Multivariate analysis revealed that pathologic
stage had an independent prognostic value (p < 0.05). The independent prognostic
value of p53 protein overexpression did not quite reach statistical significance
(p = 0.07). p53 protein nuclear overexpression appears to be a relatively weak
prognostic indicator for patients with invasive transitional cell carcinoma of
the renal pelvis and ureter.
PMID- 9644784
TI - Cytokeratin 8/18 levels in patients with prostate cancer and benign prostatic
hyperplasia.
AB - OBJECTIVES: Recently, tissue polypeptide-specific antigen (TPS), a cytokeratin 18
marker, was described to be discriminative between cancer of the prostate (CaP)
and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes
both cytokeratin 8 and 18 fragments, is discussed to improve sensitivity and
specificity of TPS. We investigated whether Cyfra 8/18 serum concentration
discriminates between patients with clinically localized CaP and BPH. METHODS:
Serum Cyfra 8/18 levels were determined in patients with untreated CaP before
radical prostatectomy (pT1-3pNoMo; n = 11) and with histologically confirmed BPH
(n = 22). Cyfra 8/18 concentration was correlated to the prostate-specific
antigen (PSA) concentration. RESULTS: Median Cyfra 8/18 level was 0.64 ng/ml in
CaP patients and 0.57 ng/ml in BPH patients. This difference is statistically not
significant (p = 0.91). Furthermore, no correlation to PSA levels could be
established (CaP: r = 0.036; BPH: r = 0.09). CONCLUSION: In contrast to a recent
report we found the Cyfra 8/18 serum concentration to be a nondiscriminative
parameter between CaP and BPH.
PMID- 9644785
TI - Biphasic action of phenylephrine on the Ca(2+)-activated K+ channel of human
prostatic smooth muscle cells.
AB - The elevation of cytosolic Ca2+ ([Ca2+]i) is known to regulate smooth muscle
contractility. A physiological concentration of phenylephrine induced the
elevation in [Ca2+]i of human prostatic smooth muscle cells; however, contraction
of prostatic tissues in vitro needs a higher concentration of phenylephrine than
the physiological level. To investigate this discrepancy, we investigated the
functional importance of the Ca(2+)-activated K+ channel (KCa channel) of human
prostatic smooth muscle cells in phenylephrine-induced contraction. Using the
patch-clamp technique, the KCa channel of human prostatic smooth muscle cells was
activated by phenylephrine at a physiological concentration (10(-7)-10(-5) M) but
was inhibited at a higher concentration (10(-4)-10(-3) M). Phenylephrine (10(-3)
M) also inhibited the KCa channel which was activated by 10 microM A23187, a
calcium ionophore. Similar inhibition was obtained with 1 microM phorbol 12
myristate 13-acetate, an activator of protein kinase C (C-kinase). Both
inhibitions were reversed by subsequent application of 1 nM staurosporine, a
protein kinase inhibitor. These results suggested that C-kinase mediated the
phenylephrine-induced inhibition of the KCa channel. In this study, a
physiological concentration of phenylephrine induced activation of the KCa
channel of human prostatic smooth muscle cells, which brought about membrane
hyperpolarization and relaxation of human prostatic smooth muscle cells. The
regulation of the KCa channel by phenylephrine may explain the need of a high
concentration of phenylephrine for the contraction of prostatic tissue.
PMID- 9644786
TI - Absorption of epirubicin instilled intravesically immediately after transurethral
resection of superficial bladder cancer.
AB - As postoperative adjuvant therapy for superficial bladder cancer, intravesical
instillation therapy is commonly conducted. In this case, from the view point of
prevention of intraoperative dissemination, commencement of instillation therapy
at an early postoperative period is preferred. However, increased drug
permeability is suspected because of damage to the bladder mucosa during
operation. Therefore, this study was conducted to investigate the plasma level of
epirubicin (EPI) instilled immediately after transurethral operation. EPI (20
mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral
operation, and retained in the bladder for 1 h. Blood samples were obtained
before instillation, as well as 30, 60, 120 and 240 min after instillation, and
EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40
ml group (n = 5) were < 2.5 and < 2.0 at 30 and 60 min, respectively, after which
they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and <
3.0 after 30, 60 and 120 min, respectively, and after 240 min it was
undetectable. Intravesical instillation of EPI immediately after a transurethral
operation causes a small increase in the plasma level and it is thought to cause
small systemic side effects.
PMID- 9644787
TI - Renal needle biopsy along the retrograde puncture line of the renal calyx: a new
promising technique.
AB - The Biopty-gun is a useful tool in conducting percutaneous renal biopsies, but
bleeding is still a significant complication. To reduce the rate of severe
bleeding complications, we attempted a new method of renal needle biopsy using a
retrograde access technique. Retrograde puncture of the renal calyx was performed
using the Lawson nephrostomy kit. The 18-gauge needle of the Bioptygun was
inserted along the puncture wire and fired. A 7-french pigtail catheter was
retained in the renal pelvis for a few days following the procedure. This biopsy
is a promising and safe technique.
PMID- 9644788
TI - Operative course of transurethral resection of the prostate and progression of
prostate cancer.
AB - Surgery has the potential to disseminate cancer cells, and we therefore
hypothesized that extensive transurethral resections of the prostate (TURP) would
be followed by a worse prognosis than minor ones. For this purpose, the
association between the extent of surgery, disease progression, and mortality was
studied in 138 patients with prostatic cancer who had undergone TURP. The results
show that a large bleed (> or = 275 ml) indicated a slightly increased relative
risk of general progression of the cancer (relative risk (RR) = 1.9, 95%
confidence interval (CI) = 0.9-4.1) and death (RR = 1.5, CI = 0.6-3.3). Other
parameters of extensive surgery, such as the operating time and fluid absorption,
were not associated with increased risk. Patients with a medical disease,
however, such as hypertension and congestive heart failure, had a significantly
higher relative risk of general progression (RR = 2.7, CI = 1.2-6.1) and death
from prostatic cancer (RR = 4.6, CI = 2.0-10.7) in addition to an increased
relative risk of death from other causes (RR = 3.7, CI = 1.3-10.5). We conclude
that concurrent medical disease, but not an extensive TURP, worsened the
prognosis of patients with prostatic cancer who underwent TURP.
PMID- 9644789
TI - Primary erectile dysfunction in combination with congenital malformation of the
cavernous bodies.
AB - Primary erectile dysfunction in combination with congenital malformation of the
cavernous bodies has only rarely been reported. We report on 2 young patients
with different congenital malformations. To our knowledge this is the first time
partial aplasia of the distal part of the cavernous bodies is described, whilst
complete isolation of the cavernous bodies in combination with veno-occlusive
dysfunction has yet been described in 3 cases. After complete examination,
including penile angiography and cavernosometry, a surgical correction with a
fully satisfying result was achieved in the patient with distal aplasia. In case
of isolated cavernous bodies with severe veno-occlusive dysfunction, the
implantation of a penile prosthesis remains the treatment of choice.
PMID- 9644790
TI - Idiopathic partial thrombosis of the corpus cavernosum.
AB - A case of spontaneous, partial, unilateral thrombosis of the corpus cavernosum is
described. A 35-year-old white male presented with a painful mass in the perineum
without priapism. Diagnostic evaluation with sonography and magnetic resonance
imaging revealed a thrombosis in the left posterior corporal body. Treatment
consisted of intravenous heparin followed by prophylactic acetylsalicylic acid.
The thrombosis resolved spontaneously over several months without sequelae.
Conservative management of this rare disease appears to be possible and safe.
PMID- 9644791
TI - Erectile dysfunction due to single vessel failure: diagnosis and surgical
treatment.
AB - We report on the successful surgical treatment of venous single vessel disease in
a patient presenting with erectile dysfunction. We stress the necessity of
accurate diagnostic workup which enables the identification of rare cases that
can be cured surgically.
PMID- 9644792
TI - Isolated fibrinoid vasculitis in renal angiomyolipoma.
AB - Renal angiomyolipoma is a tumor composed of a mixture of thick-walled blood
vessels, smooth muscle, and mature adipose tissue. It may present as a single
unilateral lesion or as a multifocal uni- or bilateral neoplasm. The histologic
spectrum of angiomyolipoma is wide but as far as we know intratumoral fibrinoid
vasculitis has not been described in the tumor. This is the first report of
isolated intratumoral fibrinoid vasculitis observed in two nodules of a
unilateral multifocal renal angiomyolipoma. The vasculitis arose in a
hypertensive 62-year-old woman who presented with a history of dull right flank
and low back pain of 3 months' duration. There were no signs of generalized
disease. Immunophenotyping of the vascular cellular infiltrate disclosed abundant
T lymphocytes, significant numbers of histiocytes, and absence of B lymphocytes.
The diagnosis of isolated intratumoral arteritis depends on the exclusion of
systemic disease. It is important to distinguish cases like this one to avoid
misdiagnosis and to prevent unnecessary treatment.
PMID- 9644793
TI - Pyelovenous fistula: an uncommon cause of 'essential haematuria'.
AB - Haematuria from obscure lesions of the kidney sometimes pose both diagnostic and
therapeutic challenge. Recently, we managed a patient in whom a confident
diagnosis of pyelovenous fistula was made.
PMID- 9644794
TI - Pelvic arteriovenous aneurysm caused by transurethral resection of the prostate:
successful management by intra-arterial embolization.
AB - We report a case of pelvic arteriovenous aneurysm caused by transurethral
resection of the prostate. An abnormal vascular system was successfully managed
by intra-arterial embolization using N-butyl cyanoacrylate in combination with
platinum coil.
PMID- 9644795
TI - A mullerian prostatic cyst protruding into the base of the urinary bladder.
AB - The unique appearance of a midline prostatic cyst is reported. The cyst presented
as a round-shaped filling defect at the base of the urinary bladder during an
intravenous pyelography study. Transabdominal sonography showed the mass to be a
midline prostatic cyst. The sonographic features of the mass and its location are
the hallmark of a mullerian duct prostatic cyst. Midline prostatic cysts are
discussed and the features differentiating mullerian duct cysts from utricle
cysts are emphasized.
PMID- 9644796
TI - Prostatic adenocarcinoma diagnosed by prostate-specific antigen analysis of
pleural fluid.
AB - Adenocarcinoma of the prostate may result in a malignant pleural effusion.
However, most of these cases involve patients with either a known primary
prostate cancer or radiographic evidence of pulmonary metastases. Occasionally,
the initial diagnosis of prostate cancer is made because of prostate-specific
antigen (PSA) staining cells in the pleural fluid. We report a case of
adenocarcinoma of the prostate that was suspected only because of an elevated PSA
in the pleural fluid in a patient who lacked malignant cytology, a history of
prostate cancer, and radiographic evidence of pulmonary disease.
PMID- 9644797
TI - Treatment of a recurrent bulbar urethral stricture after Urolume wallstent
implantation with a second inner Urethrospiral-2 urethral stent.
AB - Although the Urolume wallstent has been proven to be effective in the treatment
of bulbar urethral strictures, in some instances obstruction may recur. We
present a patient in whom recurrent stricture after wallstent implantation was
managed by insertion of a second inner Porges Urethrospiral-2 stent inside the
first one.
PMID- 9644798
TI - Long-term outcome of a patient with intrascrotal extratesticular malignant
schwannoma.
AB - We have the opportunity to present a rare case of late local recurrence after
treatment of intrascrotal extratesticular malignant schwannoma with
rhabdomyoblastic features in an adult man. As our case is the first in the
literature, we want to inform the reader about the long-term follow-up of our
patient and suggest that these tumors may have a long survival and late
recurrences may occur even after 5 years postoperatively.
PMID- 9644799
TI - [The characteristics of the spatial organization of the human EEG in ketamine
altered consciousness].
AB - Spatial organization of human EEG was studied by means of topographic mapping
methods with the multiparametric data estimations in the state altered by
ketamine in terms of the concept of coherent structures of brain electrical
activity. Two main features of the altered state of consciousness were reflected
in the opposite shifts: an increase in the spatial synchronization in the left
hemisphere (especially, in the posterior area) and its decrease in the left
frontal and right temporal one. The obtained data are discussed from the
viewpoint of dissociative effects of ketamine at the neurochemical and
neurophysiological levels.
PMID- 9644801
TI - [The human electroencephalogram during the mental recall of emotionally colored
events].
AB - The role of the left and right brain hemispheres in mental reproduction of
emotional states by human subjects was analyzed using a new technique of EEG
power spectral analysis in narrow frequency bands. At the maximal emotional
tension joy was shown to be characterized by an increase in the alpha peak
frequency. On the contrary, sorrow accompanied by a decrease in this value. We
think that the left hemisphere (as well as the right one) participate in the
development of emotional reactions.
PMID- 9644800
TI - [The effect of a lesion of the subcortical conducting pathways on the electrical
activity of the human cerebral cortex].
AB - Simultaneous consideration of EEG, neurological, and imaging data obtained with
sequelae of ischemic stroke during rehabilitation allowed us to verify the
organic nature of some EEG phenomena. It was shown that stroke-induced impaired
circulation in the area of the middle brain artery gave rise to deviant local
cortical electrical activity (EA) in the form of polymorphic theta and delta
waves or groups of theta waves. The character of such activity depended on the
lesion size and extent of blood supply deficit in the damaged area. Decrease in
the lesion size and restoration of blood supply during rehabilitation were
accompanied by changes in the local deviant EA: the polymorphic slow-wave
activity was replaced by single alpha and theta sharp waves. The restoration of
motor functions was less successful in cases with the local deviant EA localized
in the caudal part of the cortex.
PMID- 9644802
TI - [The effect of vasopressin on hippocampal slices from trained rats].
AB - Vasopressin effects were compared in hippocampal slices of control and
conditioned rats. Continuous presentation both of paired and unpaired conditioned
and unconditioned stimuli induced an increase in sensitivity of hippocampal
neurons to vasopressin. This effect consisted in a complex biphasic reaction
(excitatory-inhibitory modulation of population spike amplitude) to peptide
application similar to the reaction of the control slices to the increased
peptide concentration. The excitatory increased with the number of stimuli
presentations and did not depend on the factor of learning. The inhibitory phase
increased to a greater extent with the number of paired stimulations. It is
suggested that the enhancement of depression by vasopressin in the trained
animals in comparison with the active control most probably results from
intracellular Ca2+ accumulation during conditioning.
PMID- 9644803
TI - [The dependence of learning an active avoidance reaction on overcoming a problem
solving situation in a shuttle box].
AB - The two-way avoidance procedure dramatically differs from the one-way procedure
in rate of learning. The present study was conducted to prove that retardation of
the two-way avoidance acquisition resulted from development of the behavioral
conflict tendency not to reenter the previous shock compartment. Cluster analysis
of avoidance response indices divided rats into three distinctive classes. The
occurrence of avoidance, escape, and freezing responses in the first session was
analyzed in these three groups. Freezing during the shock action reflected the
conflict tendency and showed a negative correlation with avoidance response
indices. Only the rats which overcame the conflict and performed at least one
avoidance reaction toward the end of the first session significantly improved
their avoidance score in the following session. Discriminant analysis of indices
of the three reaction types in the first session revealed sufficiency of these
indices for prediction of the success in avoidance learning in subsequent
sessions. Our results proved the hypothesis formulated previously that the
conflict situation inherent to the two-way shuttle box procedure retarded the
active avoidance acquisition. A number of trials have to be reserved in the first
session for solving the conflict situation (direct effect on the rate of
learning). The conflict intensity which directly effects the avoidance
performance in the first session, presumably, influences learning in subsequent
sessions (secondary effect on learning).
PMID- 9644804
TI - [The study of individual differences as a method for dividing into stages the
acquisition of a complex reflex].
AB - Two-way active avoidance learning is a complex task characterized by a high level
of interindividual variability. We have demonstrated in our previous paper that
rats with different rate of learning vary in expression of freezing responses,
which reflects a conflict tendency not to re-enter the previous chock compartment
[4]. In the present work we analyzed as main indices the proportions of
avoidance, rapid escape, and freezing responses and their distribution within a
session. Sequences of occurrence of these three types of responses were examined
in groups of rats with different success of avoidance learning. The obtained
results confirmed a hypothesis that overcoming the conflict tendency was a
separate stage of learning which preceded avoidance response appearance and
subsequent stabilization. Only in rats which failed to learn and develop
avoidance responses within the first session, freezing responses were observed in
successive session being indicative of reappearance of the conflict tendency. The
intensity of the conflict tendency did not depend on the type of the first
response of an animal (fleeing or freezing) to an unexpected aversive stimulus.
PMID- 9644805
TI - [The effect of serotonin antibodies on the behavior of C57Bl/6 mice in an open
field and on the level of monoamines in the brain structures].
AB - Mice of C57BL/6 strain were singly injected intraperitoneally with antibodies
(AB) to serotonin (5-HT). The "open-field" testing in different periods after the
AB injection revealed a depression of behavior within 1.5 h which changed for
activation within 1 day and, again, depression within 5 days after the injection.
The analysis of neurotransmitter content in the sensorimotor cortex and
hypothalamus revealed increased levels of serotonin and, especially, dopamine in
the cortex within 1 day. The cortex serotonin level within 5 days was also
increased. The possible mechanisms are discussed of neurotropic action of AB to 5
HT.
PMID- 9644806
TI - [The effect of piracetam on the behavior of Nauphoeta cinerea cockroaches in an
open field].
AB - For 30 min the behaviour of 164 male cockroaches was studied in an "open field"
analog. At the 31st min the electrical light was switched on and the examination
was continued for 10 min. It was found out that the insects placed in the "open
field" and subjected to a sudden illumination behaved in a similar way. After the
initial freezing a sharp increase in the motor activity was observed with
subsequent habituation. Per os administration of 200-400 mg/kg of piracetam (a
solution of 5 mg of the drug and 500 mg of honey in 5 ml of water) did not change
the freezing period but accelerated habituation and decreased the locomotion
augmentation caused by the light. The obtained data suggest that piracetam
improves memory and non-associative learning and exerts a stress-protective
effect on cockroaches.
PMID- 9644807
TI - [Posttetanic changes in the background gamma oscillations in interhemispheric
interactions].
AB - The influence of high-frequency microstimulation (HFMS) of one of the hemispheres
on the parameters of spontaneous gamma-oscillations in the neural network
containing callosal cells of the motor cortex of both hemispheres. There were
three modes in the background oscillation periods distribution, which
corresponded to the frequencies 40-60, 70-100, and 100-200 Hz. These oscillation
frequencies were also revealed after the HFMS in neural interactions of the
cells, which were active before the HFMS; the frequency 40-60 Hz, which dominated
before the HFMS, became even more pronounced. The same three groups of
oscillation frequencies were found in the activity of cells which became active
after the HFMS. The expression of oscillations, the number of oscillatory
interactions, as well as the number of neuronal pairs with additional
synchronization decreased after the HFMS, which suggests a decrease in
synchronization. Taking into account the results of simulation experiments that
the frequency of gamma-oscillations is determined by the strength of inhibitory
and excitatory input, we suggest that the long-term posttetanic modifications in
the efficacy of synaptic inputs of the neurons of both hemispheres underlie the
observed posttetanic changes.
PMID- 9644808
TI - [The hypercolumns of the guinea pig visual cortex. The heterogeneity and
multilevel topical organization of the projections].
AB - Spatial distribution of neural responses to spots, slits, and bars in the guinea
pig visual cortex reveals hypercolumns like those in the brain of higher mammals.
The regular heterogeneities of topic projections within and between hypercolumns
(reflected in a distribution of focal potentials in different cortical areas)
suggest that the described columns are discrete cortical zones (or macromodules)
about 0.6 mm in size. They consist of 7-10 on/off polar orientation micromodules
about 0.2 mm in size. In turn, the latter also have the inner topical
organization of their projections. Consequently, the described topical
projections have a multilevel hierarchical organization of accordance with
different complicity of neural structures. Taking into account the known polar
structure of hypercolumns we think that it provides a possibility of comparison
between the vectors of signals and polar structures. There are reasons to believe
that this is a principle condition for signal recognition.
PMID- 9644809
TI - [The initial level of motor activity determines the directivity of the motor
effect of apomorphine].
AB - In male mice of BALB/c and SHR strains with the highest base level of locomotion
and rearings apomorphine (5 mg/kg) decreased these forms of motor activity while
in C57BL/6 mice with the lowest base level of motor activity apomorphine
increased it. In mice of C57BR and C3H/A strains with intermediate base level
there was a tendency for an increase in activity. Extinction of exploratory motor
activity in BALB/c as a result of four consecutive testings in the same
experimental chamber with hourly intervals induced a decrease in activity of the
animals by half. Being injected against this background the same dose of
apomorphine (5 mg/kg) twice increased locomotion and rearings in these mice.
PMID- 9644810
TI - [The striatum in the system of the central mechanisms of biorhythm control].
AB - Striatum as a primary oscillatory brain structure participates in organization of
the short-period pharmacogenous rhythms (amphetamine-induced stereotypy and
haloperidol catalepsy) and time course of forced swimming. This form of activity
can be controlled by the functional connections of the striatum with
suprachiasmatic hypothalamic nuclei and pineal gland.
PMID- 9644811
TI - [The properties of the benzodiazepine receptors of the rat cerebellum 6 months
after korazol-induced kindling and recurrent seizures].
AB - It was shown that the increased brain seizure readiness persisted within 6 months
after termination of corazol kindling. Seizures of the same severity as during
kindling (corazol injection in a dose of 20 mg/kg) were reproduced by corazol
injection in a dose of 30 mg/kg. In contrast to the control rats, in this
situation an autoenhancement of seizures was observed in the kindled animals.
Acute corazol seizures induced a decrease in Bmax and Kd of 3H-diazepam binding
with benzodiazepine receptors (BDR) in the cerebellum of the 10-months-old
control rats white the young animals demonstrated only a decrease in Bmax of
binding. In 6 months after kindling termination the BDR activity (Bmax) was
reduced by one half. However, we think that the increase in Bmax is not
responsible for persistence of the increased seizure readiness. It seems possible
that down regulation of receptor activity develops independently of kindling but
in response to long-lasting corazol application. Probably, Bmax spontaneously
decreases after the termination of the long-term corazol application. The single
dose of corazol (30 mg/kg) restores the changes in BDR density to the level when
seizure readiness has been just fixed (6 months after kindling termination),
independently of the primary receptor density.
PMID- 9644812
TI - [The electrical activity of the brain structures in an experimental depressive
syndrome induced by the systemic administration of 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine to rats].
AB - In rats injected with neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) the development of experimental depressive syndrome was accompanied by
local epileptiform activity in the caudate-putamen complex and by reorganization
of electrical processes in the brain. The spectral power density in the caudate
putamen in the delta range was increased in the formative stage of depressive
syndrome (day 3-4 from the beginning of MPTP administration) and in the stage of
behaviour recovery (a week after the withdrawal) as compared to control rats. On
the contrary, the spectral power in the alpha range was decreased at the peak of
depression (day 11-12 from the beginning of neurotoxin administration) and a week
after the withdrawal as compared to the initial value. In the formative stage of
depressive syndrome the spectral power in the delta range was increased in
hippocampus whereas in sensorimotor cortex it was decreased at the frequency 6 Hz
compared to control. It is suggested that a new pathodynamical organization is
formed in the CNS of animals in response to MPTP administration, which is thought
to be a neuropathophysiological basis of depressive syndrome.
PMID- 9644813
TI - [Brain monoamine oxidases in rats selected for their predisposition to pendular
like movements of the head and shoulder girdle].
AB - Brain MAO activity was studied in male rats from the strains bred from Wistar
stock for predisposition to pendulum movements (PM+) and for the absence of such
predisposition (PM-). By 16.00 o'clock, in PM+ rats MAO A activity significantly
increased in the brain hemispheres and decreased in the brainstem. By this time,
MAO B/MAO A ratio decreased in the hemispheres and increased in the brainstem.
Emotional (immobilization) stress induced an increase in activity both of MAO A
and MAO B in the brainstem of PM+ rats and increase only in MAO A activity in the
hemispheres of PM- rats. Actinomycin D abolished the effect of stress on MAO A
and MAO B in PM+ rats but increased MAO A activity in the hemispheres of PM-
rats. Possible molecular modifications are discussed in regulation of MAO
activity in PM+ rats.
PMID- 9644814
TI - [The characteristics of the functional activity of the brain serotoninergic
system in the manifestation of natural and pathological anxiety in mice: the
effect of the genotype].
AB - Anxiety was estimated in intact male mice of C57BL/6J (C57) and (CBA) and CBA/Lac
(CBA) strains and in males of both strains after the repeated experience of
social defeats (losers) in 10 daily aggressive confrontations. A plus-maze test
for behavior in a novel situation and a partition test for communicative activity
were applied. Tryptophan hydroxylase (TPH) activity, 5-hydroxytryptamine (5-HT)
and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the midbrain,
hypothalamus, amygdala, hippocampus, and striatum in losers and controls (5 days
of individual housing of intact animals). Intact C57 mice which demonstrated
active avoidance in the maze had reduced TPH activity in the all studied brain
regions compared to the intact CBA mice with passive behavior. The 5-HT
catabolism in intact C57 was lower in the midbrain and hypothalamus and higher in
amygdala, hippocampus, and striatum than in CBA mice. Chronic social stress led
to expressed anxiety revealed by both tests in C57 losers in contrast to CBA
ones. This anxiety was accompanied by an increase in 5-HIAA level and 5-HIAA/5-HT
ratio in the midbrain as well as by an increase in 5-HT level and decrease in 5
HIAA level and 5-HIAA/5-HT ratio in the hippocampus of C57 losers in comparison
with the controls. Flesinoxan (0.5 mg/kg, i.p.), 5-HT1A receptor agonist, changed
the communicative behavior of controls but was ineffective in losers. Thus, a
decrease in sensitivity of 5-HT1A receptors was suggested in stress-induced
anxiety of C57 losers. The less expressed anxiety in CBA losers was associated
with less expressed changes in serotonergic metabolism. It is concluded that
serotonergic mechanisms of pathological anxiety induced by the long-term social
stress and those of natural anxiety in intact mice are different.
PMID- 9644815
TI - [A quantitative morphological study of the effect of partial visual deprivation
on the formation of 2 types of Wulst neurons in pied flycatcher nestlings].
AB - Neurons of the Wulst area (analogous to mammalian visual cortex) were studied
with the method of computerized morphometry (6 parameters) in frontal Golgi
stained sections of pied flycatcher nestlings which were binocularly deprived
since the age of 1-1.5 days post-hatching. The current study was focused on two
types of neurons: spiny stellate and small spineless stellate-like cells. It was
found that the visual deprivation not only slowed down the morphogenesis of these
neurons but also caused the constructive changes--increase in the number of foci
of maximal dendrite branching--in spiny stellate neurons which we had earlier
defined as projective cells. Changes in small spineless stellate-like neurons
(earlier defined as intercalate cells) were of, mostly, opposite direction. In
the latter neurons we observed a reduction of the number of dendrites and
dendrite branches. Opposite changes in different cell groups caused by the
limitation of sensory input may, on the one hand, point to a difference in
functional connections of ascending afferent fibers with different types of
neurons, and, on the other hand, indicate a different degree of the influence of
visual experience on the development of these neurons.
PMID- 9644816
TI - [The place of the action of the serotoninergic system in the 2-stage process of
the formation of latent inhibition in rats].
AB - Activation of rat brain serotonergic system (injections of a selective serotonin
reuptake blocker sertralin) at the stage of pre-exposition of the situation
stimulus (placing into the illuminated compartment of the dark-light shuttle-box)
intensified subsequent development of the latent inhibition at the stage of
conditioning, which was measured by the latent period of transition to the dark
compartment during the first testing after reinforcement of such transition with
electrical shock.
PMID- 9644817
TI - [The staining of the central neurons in the pteropod mollusk Clione limacina with
fluorescein-labelled alpha-bungarotoxin].
AB - FITC-labelled alpha-bungarotoxin (alpha BT[FITC]) was used to identify
acetylcholine (ACh)-sensitive neurons in the central nervous system of pteropod
mollusc Clione limacina. Two small symmetrical neurons were stained with alpha
BT[FITC] on the dorsal surface of the cerebral ganglia. The staining was highly
specific as it was completely blocked by preincubation in alpha-bungarotoxin
[alpha BT] at very low concentration (10(-9) M). Nicotinic agonists and
antagonists efficiently prevented alpha BT[FITC] staining while muscarinic
agonists and antagonists had no effect. These findings confirm the suggestion
that alpha BT[FITC] binds to nicotinic ACh receptors. The possible role is
discussed of alpha BT[FITC]-stained cells in the complex of hunting behavior of
Clione.
PMID- 9644818
TI - [The problem of the origin of intellect and evolutionary biocybernetics].
AB - The discussion proposed by L. M. Chailakhian in developed concerning the problem
of the origin of the natural intelligence. It is stressed that studying the
origin of logical thinking is very important. It is argued that the problem of
the intelligence origin should be analyzed within the framework of general
investigations of the evolution of biocybernetical system. This approach can
constitute the powerful branch of science named evolutionary biocybernetics. The
main lines of inquiry are characterized. The strategy is outlined of development
of evolutionary biocybernetics: creation and development of basic mathematical
models which characterize the key "intellectual inventions" of biological
evolution. The examples are given of the models (the model of dominanta origin
and the model of functional system in correspondence with P. K. Anokhin's ideas),
which can be developed in the immediate future. The approaches are outlined to
development of these models.
PMID- 9644819
TI - [The orienting reaction and the conditioned reflex--a reaction to a predictable
situation].
PMID- 9644820
TI - [The functional asymmetry of the emotions].
AB - A considerable body of neuropsychological and psychophysiological evidence
suggests that the left hemisphere of the human brain is related to positive
emotions, whereas the right hemisphere is related to negative emotions. R.
Davidson and W. Heller (1993) suggested that it is determined by the ratio
between the activities of the left and right regions of the frontal cortex.
Comparison of these premises with those proposed by need-informational theory of
emotions suggests that the right frontal cortex preferentially deals with
pragmatic information (earlier experience stored in memory) required for
satisfaction of the actual need, whereas the left frontal cortex processes most
recent and currently available information. Unit activity of the prefrontal
cortex was investigated in rats during stimulation of the emotionally positive
(lateral hypothalamic area) and negative (dorsomedial tegmentum) structures. The
asymmetry was revealed in neuronal responses: the prevalence of the left
hemisphere during emotionally positive stimulation and of the right hemisphere
during negative stimulation. Further research should provide more knowledge on
the features of information processing by the left and right frontal cortical
regions in humans and animals and elucidate the nature of interaction of these
areas with need--and information-related cortico-limbic structures of the brain.
PMID- 9644821
TI - Discrepantly poor verbal skills in poor readers: a failure of learning or
ability?
AB - Poor verbal skills in poor readers have long been reported in the literature.
There have been many attempts to understand the interaction between poor verbal
ability and poor verbal achievement. The methodological problems are
considerable, including the measurement of verbal ability, which has been
confounded by previous learning. A new reasoning test, the VESPAR, has been
designed to measure novel problem solving and thus to be less reliant on acquired
verbal skills. One hundred and seventy 14-year-olds completed the VESPAR, the
Cognitive Abilities Test (CAT) and a single-word reading test. Overall, verbal
scores were weaker than spatial scores. A subgroup of 38 pupils with particularly
marked discrepancies between verbal and non-verbal CAT was identified. The
especially discrepant pupils were matched with other non-discrepant pupils from
the year group for either verbal or non-verbal CAT. The discrepant group's
reading was at the same level as the matched verbal CAT group. However, the
primary verbal ability of the discrepancy group, as measured on the VESPAR, was
greater than the matched verbal CAT group. This raises the possibility that CAT-
but not VESPAR-discrepant pupils may be at particular risk of under-achievement
in the verbal domain.
PMID- 9644822
TI - Derivation of a homesickness scale.
AB - A 33-item measure of homesickness (the Homesickness Questionnaire, HQ) was
derived from features of grief modified for the circumstance of separation from
home. In three samples of year 1 students (N = 264) during their first year at
university, total HQ scores were highly correlated with a single-item measure of
homesickness used in previous studies, and 28 items showed significant
differences between subgroups divided on the basis of the single-item scores.
Previous findings that homesick students show more health and psychological
symptoms, and cognitive failures, were supported by further comparisons between
the two groups, and a meta-analysis of four studies. Factor analysis of the HQ
indicated two factors, disliking the university, and attachment to the home,
which are consistent with both the separation and strain models of homesickness.
Correlations with other variables, and sex differences in the factor scores,
further supported the distinction between these two aspects of homesickness.
Women showed higher levels of intrusive thinking about the homesickness, but this
was mediated by their higher scores on the attachment factor of the HQ. There was
no sex difference in avoidant responses to homesickness.
PMID- 9644823
TI - Differences between implicit and explicit acquisition of a complex motor skill
under pressure: an examination of some evidence.
AB - Masters (1992) argued that an implicitly acquired motor skill is less likely to
fail under pressure than an explicitly acquired skill. He demonstrated this by
showing that induced anxiety led to differences in the golf putting performance
of groups who had acquired the skill implicitly and explicitly. We replicated
Masters' basic findings but our results suggest that the difference in
performance under pressure is more readily explained in terms of differences
between the learning and testing conditions. Our results are consistent with an
explicit learning account of the putting task and we found no support for the
claim that implicit and explicit learning of motor skills are differentially
affected by anxiety.
PMID- 9644824
TI - Serial report and item recognition of novel visual patterns.
AB - Previous studies of memory for novel visual patterns have reported how item
recognition varies across serial positions, but have neglected serial order
memory. In Expts 1 and 2 participants reported the order in which short series of
novel patterns had been presented. The results showed markedly bowed serial
position curves similar to those reported for sequences of verbal items or
spatial locations. Concurrent articulation reduced performance in the serial
report task relative to the memory task alone (Expt 2) or concurrent tapping
(Expt 3) suggesting that a verbal component was involved. When two-alternative
forced choice tests were used to test memory for the configuration of each
pattern in the series, no primacy or recency was found (Expt 4). In Expt 5 the
presentation of a series of five items was followed at random by either a serial
report or the two-choice item recognition task. The serial position curves for
the two tasks remained different, suggesting that encoding strategies were not
responsible. The results show that bowed serial position curves are found when
judgments of serial order are required, even when phonological coding is
discouraged, whereas memory for item descriptions is independent of serial
position. The implications for current conceptualizations of short-term memory
are discussed.
PMID- 9644825
TI - A species-specific satellite DNA from the entomopathogenic nematode
Heterorhabditis indicus.
AB - An AluI satellite DNA family has been cloned from the entomopathogenic nematode
Heterorhabditis indicus. This repeated sequence appears to be an unusually
abundant satellite DNA, since it constitutes about 45% of the H. indicus genome.
The consensus sequence is 174 nucleotides long and has an A + T content of 56%,
with the presence of direct and inverted repeat clusters. DNA sequence data
reveal that monomers are quite homogeneous. Such homogeneity suggests that some
mechanism is acting to maintain the homogeneity of this satellite DNA, despite
its abundance, or that this repeated sequence could have appeared recently in the
genome of H. indicus. Hybridization analysis of genomic DNAs from different
Heterorhabditis species shows that this satellite DNA sequence is specific to the
H. indicus genome. Considering the species specificity and the high copy number
of this AluI satellite DNA sequence, it could provide a rapid and powerful tool
for identifying H. indicus strains.
PMID- 9644826
TI - Polymorphic microsatellites in Simulium damnosum s.l. and their use for
differentiating two savannah populations: implications for epidemiological
studies.
AB - In West Africa, Onchocerca volvulus, the cause of human onchocerciasis, is
transmitted by sibling species of the Simulium damnosum complex. Little is known
about blackfly intraspecific variability and its consequences on vectorial
capacity. This study reports the use of microsatellite markers for
differentiating populations of S. damnosum s.l. Five microsatellite loci were
characterized and used to analyze individuals from two savannah populations in
Mali, 120 km apart. Four loci were highly polymorphic, having 8-12 alleles per
locus and gene diversities ranging from 77.9 to 88.2%. A significant heterozygote
deficiency was observed in the two populations. This may arise from inbreeding,
population structure (the Walhund effect), or the presence of null alleles. To
test this last hypothesis, new primers were designed for two loci and used to
analyze homozygous individuals. After correcting for null alleles, heterozygote
deficit persisted. Population subdivision in the two foci remains the most likely
explanation. Our results indicate that microsatellite markers could differentiate
fly populations, making them valuable tools for the study of population genetic
structure.
PMID- 9644827
TI - The nuclear ribosomal DNA intergenic spacers of wild and cultivated soybean have
low variation and cryptic subrepeats.
AB - The intergenic ribosomal DNA spacers (IGSs) from cultivated soybean (Glycine max)
and wild soybean (Glycine soja) were sequenced and compared with six other
legumes. These IGS sequences were 1821 bp in length in G. soja and G. max
cultivars Arksoy, Ransom, and Tokyo, and 1823 bp long in the G. max cultivar
Columbus. These represent the smallest published plant IGS sequences to data. Two
clones from each of the above five cultivars were sequenced and only 22 sites
(1.2%) were polymorphic, thereby supporting previous work that showed low genetic
variation in cultivated soybean. The amount of variation observed between
different clones derived from the same individual was equal to the amount seen
between different cultivars. The soybean IGS sequence was aligned with six other
published legume sequences and two homologous regions were identified. The first
spans positions 706-1017 in the soybean IGS sequence and ends at a putative
promoter site that appears conserved among all legumes. The second is located
within the 5' external transcribed spacer, spans positions 1251-1823 in soybean,
and includes sequences first identified as subrepeats IV-1 and IV-2 in Vicia
angustifolia. Sequences homologous to these two subrepeats were identified among
all legume species examined and are here designated "cryptic subrepeats" (CS-1,
CS-2) given the range in similarity value (79-96% for CS-1 and 60-95% for CS-2).
Comparisons of CS-1 and CS-2 sequences within individual species show that
divergence (substitutional mutations, insertions, and deletions) is sufficiently
high to obscure recognition of the repeat nature of these sequences by routine
dot plot analytical methods. The lack of subrepeats in the 5' half of the soybean
IGSs raises questions regarding the role they play in transcription termination
or enhancement.
PMID- 9644832
TI - The light gene of Drosophila melanogaster encodes a homologue of VPS41, a yeast
gene involved in cellular-protein trafficking.
AB - Mutations in a number of genes affect eye colour in Drosophila melanogaster; some
of these "eye-colour" genes have been shown to be involved in various aspects of
cellular transport processes. In addition, combinations of viable mutant alleles
of some of these genes, such as carnation (car) combined with either light (lt)
or deep-orange (dor) mutants, show lethal interactions. Recently, dor was shown
to be homologous to the yeast gene PEP3 (VPS18), which is known to be involved in
intracellular trafficking. We have undertaken to extend our earlier work on the
lt gene, in order to examine in more detail its expression pattern and to
characterize its gene product via sequencing of a cloned cDNA. The gene appears
to be expressed at relatively high levels in all stages and tissues examined, and
shows strong homology to VPS41, a gene involved in cellular-protein trafficking
in yeast and higher eukaryotes. Further genetic experiments also point to a role
for lt in transport processes: we describe lethal interactions between viable
alleles of lt and dor, as well as phenotypic interactions (reductions in eye
pigment) between allels of lt and another eye-colour gene, garnet (g), whose gene
product has close homology to a subunit of the human adaptor complex, AP-3.
PMID- 9644833
TI - Orthologous DNA sequence variation among 5S ribosomal RNA gene spacer sequences
on homoeologous chromosomes 1B, 1D, and 1R of wheat and rye.
AB - 5S ribosomal gene spacer sequences from the short-spacer arrays of wheat and rye
were isolated by PCR. The 29 new DNA sequences displayed noticeable heterogeneity
at scattered positions. Nevertheless, based on shared DNA sequence polymorphisms,
sequence alignment clearly classified the sequences into three groups. Group
specific primer sets were designed to allow chromosomal assignment by PCR on
nullitetrasomic wheat stocks, as well as on wheat-rye translocation and addition
lines. The three groups were assigned to orthologous loci 5S-Rrna-B1, 5S-Rrna-D1,
and 5S-Rrna-R1 on homoeologous chromosomes 1B, 1D, and 1R, respectively. Hence,
group-specific DNA sequence variation could be related to fixed orthologous DNA
sequence variation between 5S rRNA multigene families on the homoeologous group 1
chromosomes. In addition, members of the three groups showed fixed orthologous
length polymorphism. Four sequenced 5S-Rrna-B1 units, however, had a duplication
in the gene encoding region and are probably representatives of a nontranscribed
subfamily of 5S rDNA repeating units. The observed chromosome-specific
polymorphisms among sequences belonging to a multigene family with thousands of
copies suggests that this type of polymorphism may exist in many genes and gene
families in polyploid wheats. The implication of this finding in relation to the
construction of molecular tools for wheat-genome analysis and manipulation is
discussed.
PMID- 9644834
TI - Recovery of a marked translocation strain that will facilitate the isolation of
balancer chromosomes in the Mediterranean fruit fly, Ceratitis capitata.
AB - The results of two screens for mutations and chromosomal aberrations in Ceratitis
capitata are presented. Three dominant mutations were recovered, including Sb,
which is associated with a homozygous lethal translocation between the third and
fifth chromosomes, T(3;5)Sb, with the fifth chromosome breakpoint adjacent to y.
The T(3;5)Sb chromosome is maintained by selecting for Sb in a T(3;5)Sb, w2 Sb y2
wp/w2 y2 wp stock and can be used to distinguish between other chromosomes
carrying differential combinations of the recessive markers w2 y2 wp. The ability
to isolate particular marked chromosomes is essential in order to recover an
inversion-based balancer chromosome. In addition to the recovery of dominant
mutations, gamma-ray induced somatic mosaics of w2 and y2 and zygotic w mosaics
were found. The generation of zygotic mosaics following mutagenesis can give
mutants with a mosaic germ line that fail to breed true in the first generation.
A screen of 22,830 irradiated chromosomes failed to recover variegating alleles
of w, although such alleles might be recovered in a larger screen. The high
frequency of dominant mutations and the instability at the w locus in our stocks
implies a background level of dysgenic activity. These results have implications
for the construction and long-term maintenance of genetically modified strains.
PMID- 9644837
TI - An X/Y DNA segment from an early stage of sex chromosome differentiation in the
fly Megaselia scalaris.
AB - The sex chromosomes of the Megaselia scalaris wild-type strain Wien are
homomorphic. We studied a roughly 1.8 kb X/Y DNA segment of this strain. It
includes, at one end, the first part of a coding sequence for a protein of the
vespid antigen 5 family. Molecular differentiation between the X and Y
chromosomes has commenced, but homology, even of short DNA stretches, is still
assessable beyond doubt. The most conspicuous differences between the X and the
homologous Y segment were insertions/deletions in the noncoding region: among
them, deletions, a duplication, and an insertion of a mobile element. These
structural changes grossly disrupted homology. In comparison, base substitutions,
though more numerous, contributed little to the differentiation of the X/Y DNA
segment.
PMID- 9644838
TI - The Drosophila gene asteroid encodes a novel protein and displays dosage
sensitive interactions with Star and Egfr.
AB - The asteroid gene of Drosophila was found to lie within 189 bp of Star. Asteroid
cDNA clones were isolated and sequenced and a single putative open reading frame
was identified that encodes a novel protein of 815 amino acids with a calculated
molecular mass of 93 kilodaltons. Using cDNA probes, asteroid transcripts were
localized to the proliferative tissues of embryos and to the mitotically active
tissue anterior to the morphogenetic furrow in eye imaginal discs. Ribonuclease
protection assays identified a mutation of asteroid that acts as a dominant
enhancer of Star mutations and also enhances the Ellipse mutation, EgfrE1. Based
on these data, a model for asteroid gene function in EGF receptor signaling is
presented.
PMID- 9644840
TI - [Prevalence of respiratory diseases in the textile industry. Relation with dust
levels].
AB - Many workers in the textile industry have respiratory symptoms that are related
to their work environment. In this study we observed the dust level conditions of
eleven textile industries of the North of Portugal. The dust levels determined
were between 0.1 mg/m3 and 1.25 mg/m3, in many cases above the Portuguese
standard levels of exposure (VLE). For these dust levels we found a prevalence of
23% of workers with respiratory symptoms with occupational characteristics in
10.8%, and 5.7% presenting byssinosis. Workers exposed to cotton fibres in
spinning areas have the highest prevalence of symptoms, and reduction of the
FEV1. These characteristics were related to dust levels and were higher in the
initial phases of the spinning processes. We found no cases of byssinosis in
workers exposed to synthetic fibres, or in workers from weaving areas. Smoking
habits were related to the reduction of the FEV1, and severity of respiratory
illness but not to the presence of byssinosis.
PMID- 9644841
TI - [Diet and risk of myocardial infarction. A case-control community-based study].
AB - OBJECTIVE: To evaluate diet as a risk factor for myocardial infarction. DESIGN:
Community based case-control study. SETTING: University Hospital, Oporto.
PARTICIPANTS: First time consecutive cases of acute myocardial infarction (n =
100) and 198 community controls, older than 39 years and living in Oporto, were
compared. METHODS: Data were collected by trained interviewers using a structured
questionnaire designed to obtain information on socio-demographic, medical and
behavioural aspects, emphasising the description of diet and food habits (using a
semi-quantitative food frequency questionnaire). Controls were selected by random
digit dialing with a participation rate of 70%. Odds ratios and 95% confidence
intervals (CI) according to quartiles of nutrient ingestion were calculated using
unconditional logistic regression. RESULTS: Female controls presented
significantly higher mean intakes of protein, omega-3 fatty acids, fiber,
cholesterol and vitamin C. Male controls had a significantly higher mean daily
intake of fiber, vitamin C, vitamin E, and carotenes. After adjusting for age,
sex, education, body mass index, ethanol, smoking and total energy intake, there
was a protective effect of vitamin C (OR = 0.2, 95% CI: 0.1-0.6, for the 4th
quartile), vitamin E (OR = 0.3, 95% CI: 0.1-0.9 for the 4th quartile) and total
fiber (OR = 0.3, 95% CI: 0.1-0.9) for the 4th quartile). No significant effect
was found for trans-fatty acids, but there was a higher risk with increased
energy intake. CONCLUSIONS: This study showed that diet has an important
independent effect on myocardial infarction, a protective independent role for
anti-oxidant vitamin C and E was verified.
PMID- 9644842
TI - [Acute complications of diabetes mellitus].
AB - A retrospective study was made of 83 diabetic patients admitted to the Department
of Internal Medicine between January 1986 and December 1993, with acute
intercurrence of the disease. The authors considered some clinical features (age,
type and frequency of complication, form of presentation, causal aetiology,
laboratory findings and therapeutic options). Statistical relationships between
different populations were made using the unpaired Student's T. method. Results
were compared with those in the literature, leading to some significant
conclusions.
PMID- 9644843
TI - [Economic impact of a health care program on antibiotics].
AB - The increased use of more expensive broad-spectrum antibiotics has had an impact
on health care costs and the potential emergence of antimicrobial resistance.
Antimicrobial drug prescription programs resulted in a significant reduction in
the inappropriate use of certain antibiotics and in the pharmacy budget. The
authors present the economic impact of an antimicrobial drug prescription program
in a small community hospital.
PMID- 9644844
TI - [The use of endoprosthesis in superior vena cava syndrome caused by lung
neoplasms].
AB - We present six cases of superior vena cava syndrome caused by a malignant tumor
that were treated by percutaneous endoprostheses. The technique is described and
the results evaluated. In one case there was acute thrombosis of the
endoprosthesis that was treated by urokinase. No other complications were
observed. A patient died one month later due to progression of the tumor. The
remaining cases were asymptomatic for longer than 6 months. It was concluded that
endoprostheses for superior vena cava syndrome are efficient, with quick
improvement of the symptomatology.
PMID- 9644845
TI - [Monoclonal antibodies. General approach and radioimmunotherapy].
AB - Two major obstacles to systemic cancer therapy are the lack of specificity of
therapeutic modalities and the intrapatient and interpatient heterogeneity of
cancer cells. Because of their natural specificity, antibodies directed against
tumor specific or tumor associated antigens have been raising interest in
oncology. This article makes an overview of the basic principles of monoclonal
antibodies, their limitations and perspectives, with particular attention to
Immunoradioconjugates. The most important Immunoradiotherapy clinical studies are
also reviewed.
PMID- 9644846
TI - [Lupus anticoagulants versus antiphospholipid antibodies].
AB - The antiphospholipid antibodies (aPL) present in "antiphospholipid-protein
syndrome and autoimmune disorders" are associated with thromboembolic episodes,
such as venous and/or arterial thrombosis and fetal loss. Patients with
antiphospholipid antibodies have, by definition, laboratory abnormalities in
either coagulation assays or various solid phase immunoassays ELISA or
radioimmunoassays (RIA). These assay systems were initially thought to detect
antibodies against phospholipids. The problem was complicated when it was
reported that phospholipid is not the sole antigen but only a part of it, the
other contribution being due to b2-glycoprotein I (b2-GP I). More findings,
demonstrate that the aPL are in fact anti-b2-GP I antibodies directed against a
epitope which is expressed when b2-GP I is bound to anionic phospholipid or
another suitable surface. Recent studies have demonstrated that antibodies
related to lupus anticoagulant (LA) induce an anticoagulant activity in b2-GP I.
Some of these LA require binding to phospholipid. However, not all LA require b2
GP I as a cofactor. Human prothrombin is an antigen for some LA IgG's. Finally, a
subclassification of phospholipid-dependent coagulation test anticoagulants is
described, there appear to be several subclasses of LA, and the clinical and
laboratory criteria required to establish the diagnosis of antiphospholipid
protein syndrome is emphasised.
PMID- 9644847
TI - [Bioartificial liver].
AB - Fulminant hepatic failure remains without satisfactory medical treatment and with
a mortality rate of nearly 90%. Liver transplantation is the only chance to save
these patients. However, there is a shortage of donors and many patients die
before transplantation. It is thus necessary to develop a liver support system to
help maintain patients alive, neurologically intact until an organ becomes
available for transplantation, or ideally until hepatic regeneration. Early
systems had only a depuration function, but now these systems include hepatocytes
to replace most hepatic functions.
PMID- 9644848
TI - [Y chromosome and male infertility].
AB - Spermatogenesis is a complex physiological process characterized by an orderly
proliferation and differentiation of germ cell types, from diploid spermatogonial
stem cells to haploid spermatids, and after spermiogenesis to spermatozoa. It is
known that male reproductive capacity is deficient in about one half of infertile
couples. Effective treatment is available only for a small fraction of these
infertile men. In most cases, the cause of male infertility is unknown.
Aetiologically, male infertility may result from genetic and non-genetic causes.
Among the genetic factors known to disturb spermatogenesis, chromosomal
aberrations, involving autosomes and/or sex chromosomes, are well known. However,
molecular genetic causes of idiopathic male infertility have been accumulating in
the last years, predominantly for the Y chromosome. Localization of genes that
control spermatogenesis on Yq11 was first proposed, on cytogenetic evidence, by
Tiepolo and Zuffardi in 1976. Since then, many subsequent reports using molecular
genetics methods have supported the initial proposal by detecting submicroscopic
interstitial deletions on Yq11, present in patients with idiophatic azoospermia
and a cytogenetically normal Y chromosome. Recently, four spermatogenesis
candidate Y-linked genes (or gene families), RBM, DAZ, SPGY and TSPY have been
cloned and characterized. In the euchromatic Y chromosome long arm three
intervals--AZFa, AZFb and AZFc--were also defined. All of them may contain genes
necessary for normal spermatogenesis. All the four genes have a testis-specific
expression and three of them (RBM, DAZ and SPGY) code for ribonucleoproteins with
a single RNA recognition motif. Candidate genes with in AZFb are some members of
the RBM gene family and within AZFc are the DAZ and SPGY gene family. While AZFc
deletions are associated with azoospermia or with severe
oligoteratoasthenozoospermia, microdeletions involving AZFa or AZFb cause
azoospermia only.
PMID- 9644849
TI - [Modern ethics. Various considerations, particularly based on hospital
experience].
AB - The four basic principles of modern medical ethics are presented and discussed.
The historic evolution of the hospital is analysed concerning the organisation
and the social function of the hospital. The author presents some considerations
about the relation between the patient and the hospital, clinical investigation
and informed consent, confidentiality and technological progress. The problems of
the end-of-life of the hospitalised patient is discussed, with an overview of the
do-not-resuscitate orders.
PMID- 9644850
TI - [Aneurysms of the interatrial septum].
AB - Atrial septum aneurysms are an uncommon condition, underestimated before the
routine use of echocardiography. Their clinical importance has increased after
being associated with thromboembolic events. The authors made a review of
clinical, diagnostic and therapeutic features of this entity after reporting six
clinical cases.
PMID- 9644851
TI - [Refractory severe ulcerative colitis. Experience with cyclosporine].
AB - A case of severe ulcerative colitis refractory to steroid therapy is reported.
The authors look at cyclosporine use in this clinical setting and make a short
review of cyclosporine usefulness and major side effects.
PMID- 9644853
TI - [Therapeutic recommendations].
PMID- 9644852
TI - [Atypical radiologic features of pulmonary tuberculosis. Nodular images in
strings of balloons].
AB - Chest radiographs are an important tool for the diagnosis and follow-up. Yet the
radiographic findings can vary significantly, ranging from the so-called usual to
unusual patterns. In this paper the authors report three cases of pulmonary
tuberculosis in which the chest radiographs showed a nodular, pseudo-tumoral
pattern. Based on literature and on their own experience, the authors discuss the
frequency of this radiologic presentation in this setting and its correlation
with the immunological status of the patient, the pathogenicity of Mycobacterium
tuberculosis and the clinical presentation of the disease.
PMID- 9644854
TI - [Paragangliomas of the head and neck. Our experience].
AB - Paragangliomas of the head and neck are rare tumors of neuroectodermal origin.
However, jugulotympanic paragangliomas are the second most common tumor of the
temporal bone. Paragangliomas are recognized as benign tumors, but some show a
biological behavior similar to that of malignant lesions, such as the development
of recurrence or invasive growth patterns. We report 31 patients with a total of
35 paragangliomas who were seen in our department. Multiple paragangliomas were
found in 2 patients. Twenty-two patients had jugulotympanic paragangliomas, 11
carotid and 2 vagal paragangliomas. None of the patients had prior treatment and
the minimum follow-up was 1 year. Surgery was performed in 28 (90%), primary
irradiation in 1 (3%), and 2 (7%) refused treatment. We describe our results, the
clinical course, diagnostic methods and treatment options.
PMID- 9644855
TI - [The sensorineural component of hearing loss associated with cholesteatoma].
AB - Patients with cholesteatoma often suffer neurosensorial hearing loss with
variable bone conduction thresholds. Its origin is debated and has been
attributed to the ototoxicity of topical drugs, immune reactions, effects of
ototoxic antibiotics applied to the ear, etc. A selected series of 50 patients
who underwent surgery for chronic ear disease due to cholesteatoma in our ENT
department were studied to evaluate the possible origin of the bone conduction
component of hearing loss. Different clinical, audiological, and surgical aspects
were analyzed, including cholesteatoma site and extension, age, sex, evolution of
the symptoms, pure tone audiometry data, middle ear involvement, the operation
performed, and the occurrence of complications. Bone conduction thresholds were
reported as pure tone differential thresholds (affected vs non-affected ear). A
specific cholesteatoma-related neurosensorial hearing loss was observed that
might lead to irreversible hearing loss. Neurosensorial involvement seems to be
related mainly to the duration of symptoms, type of surgery, certain specific
clinical aspects, and complications.
PMID- 9644856
TI - [Sudden deafness. Experience at our hospital].
AB - A retrospective study was made of 60 patients (61 ears) who were hospitalized for
the study and treatment of sudden hearing loss. Data were compiled on the hearing
loss and hearing gain after treatment. Hearing loss was unrelated with age or the
appearance of vestibular symptoms. After hemodilution, steroid, and vasodilator
treatment, 47.6% showed a hearing gain of up to 20 dB. The gain was significantly
less (p < 0.05) in patients suffering vertigo. It also was less in patients who
delayed treatment and in those with severe hearing loss in the high-tone
frequencies, but these differences did not reach significance. The recovery
period ranged from 2 days to 2 months, with 48% showing improvement in the first
week.
PMID- 9644857
TI - [Epidermoid carcinoma of the nasal septum].
AB - Squamous-cell carcinoma of the nasal septum occurs infrequently and only a few
cases have been reported. Because of the small number of cases, comparisons
between treatment groups have been inadequate. Five patients with this type of
tumor are presented. All of them underwent surgery (4 as primary treatment and 1
for recurrence after radiation therapy). One patient had a local recurrence, 2
had cervical metastases, and 2 (40%) died as a consequence of the tumor. In the
squamous cell carcinoma of the nasal septum our study supports surgical resection
with wide margins combined with postoperative irradiation as the preferred
treatment with prophylactic neck dissection for tumors over 2 cm or extended to
adjacent areas.
PMID- 9644858
TI - [Laryngo-tracheoplasty in the management of infantile laryngeal stenosis].
AB - We present the results obtained in our center with laryngo-tracheoplasty for the
management of laryngeal stenosis in infants and children. Nineteen patients were
treated between 1989 and 1995. Their weights ranged from 1,200 g to 36 kg. Twenty
five operations were performed, not including endoscopic maneuvers. Fifteen
patients have been decannulated (79%). Complications were infrequent and resolved
satisfactorily. We consider that these surgical procedures should occupy a
prominent place in the management of pediatric patients with laryngeal stenosis.
PMID- 9644859
TI - [Mortality in laryngeal cancer surgery].
AB - The causes of death were studied in a series of 171 patients who died in a 5-year
follow-up period, out of a total of 631 patients who underwent different surgical
techniques for cancer of the larynx. MATERIAL AND METHODS: The case histories of
631 patients who had undergone surgery between 1974 and 1990 were reviewed; 83
did not have a 5-year follow-up and were excluded from the study. A descriptive
and inferential statistical study was made of the remaining cases to determine
the relation between cause of death and tumoral extension, primary location,
degree of tumoral differentiation, surgical technique and other data. RESULTS:
Ninety-one patients died from local or regional recurrence, 50 from distant
metastases, 20 from diseases other than the tumor, and 10 from postoperative
complications. These findings were studied with regard to factors such as tumor
extension, location, surgical technique, etc. CONCLUSIONS: The main cause of
death in surgery for cancer of the larynx was recurrence, either local, on the
tumor bed (62 patients) or regional (29 patients). The mortality rate was higher
in older patients, patients with lymph-node involvement in the postoperative
histological study, and patients with less differentiated histological forms.
PMID- 9644860
TI - [The study of postoperative infection in patients after laryngeal cancer
surgery].
AB - We evaluated wound infections in major oncological surgery for laryngeal neoplasm
and functional neck dissection. Our objective was to determine the incidence and
prevalence of infection in a group of laryngectomized patients; we evaluated the
temperature, duration of fever, and analytical findings in the postoperative
period, antibiotic prophylaxis, and the treatment of infectious complications. A
retrospective study was designed to examine the infectious complications that
appeared in 97 patients who underwent laryngectomy and neck dissection for
laryngeal carcinoma from 1994 to 1996 in an ENT department. Factors that
influence wound infection were examined: fever, granulocytopenia, preoperative
assessment, bacteriological culture, therapy and prophylaxis, and treatment. The
data were analyzed statistically and compared with findings by other authors.
PMID- 9644861
TI - [Head and neck symptoms of gastroesophageal reflux].
AB - In otorhinolaryngology, the relationship between gastroesophageal reflux (GER)
and pharyngolaryngeal disorders is well-known. In fact, many patients with GER
debut with head and neck symptoms or are first seen by an otolaryngologist. We
proposed to identify the ENT symptoms most frequently associated with GER, to
differentiate between physiological and pathological GER, and to confirm the
effectiveness of antacid treatment. Our study included 20 ambulatory patients who
presented pharygolaryngeal symptoms and clinical manifestations of GER (heartburn
and regurgitation). The patients underwent a complete ENT examination and were
referred to a gastroenterologist for esophagoscopy, manometry, and 24-hour pH
monitoring. All patients received antireflux therapy for one month (ranitidine
150 mg given twice daily). We conclude that GER produces a variety of
manifestations, but the most frequent pharyngolaryngeal symptoms and physical
findings were globus pharyngeus and erythema of the arytenoids, respectively.
Pathological GER was found in only one third of our patients and 90% responded
well to treatment.
PMID- 9644862
TI - [Risk factors in surgical wound infection in oncological surgery of the head and
neck].
AB - Although the use of antibiotic prophylaxis has significantly reduced the
frequency of postoperative wound infections, they continue to be a critical issue
in head and neck cancer surgery. A study was made of possible risk factors for
the development of these infections. A prospective study was made of 159 patients
with pharyngo-laryngeal squamous-cell carcinoma who underwent open-pharynx
surgery in order to analyze the factors associated with wound infections.
Postoperative wound infection was defined as purulent drainage or mucocutaneous
fistula formation, or both, in the first 10 days after surgery. Potential risk
factors examined were age, medical illnesses, prior surgery and radiotherapy, TNM
stage, type of operative procedure, method of reconstruction, and operative time.
The overall wound infection rate was 23%. Although the incidence of wound
infection was higher in patients who received preoperative radiotherapy, in
patients with advanced stage disease, and in those who required flap
reconstruction, the only preoperative factor that significantly increased the
rate of wound infection was the concurrence of medical illnesses (chronic
obstructive pulmonary disease and diabetes mellitus; p = 0.018). In conclusion,
the presence of prior medical diseases was the main risk factor in the
development of postoperative wound infections.
PMID- 9644863
TI - [Specialized care in pediatric otorhinolaryngological emergencies].
AB - Emergency care for pediatric patients represents a large proportion of total ENT
emergencies so we thought that it might be interesting to know the statistical
data from a tertiary hospital. These findings are the basis for planning work and
training for future specialists in different fields.
PMID- 9644864
TI - [Primary health care in otorhinolaryngology. Descriptive study].
AB - We present a one-year study describing the ENT pathology seen in a rural ENT
clinic. The study included 1,516 patients whose characteristics are described
(age, sex, diagnosis, and others).
PMID- 9644865
TI - [Middle ear carcinoma].
AB - Middle-ear cancer represents 5 to 10% of all ear neoplasms. Risk factors include
chronic suppurative pathology of the middle ear and prior irradiation. Most
malignant tumors are squamous-cell carcinomas. We report the case of a 51-year
old woman with this process. The ideal treatment is mastoidectomy or pterosectomy
followed by radiotherapy. We made a bibliographic review of the clinical
manifestations, diagnosis, treatment, and prognosis of middle-ear cancer. Five
year survival rates range from 25 to 50% in patients who undergo surgery and
radiotherapy.
PMID- 9644866
TI - [Langerhans cell histiocytosis. Report of four cases].
AB - Langerhans cell histiocytosis implies the proliferation and accumulation of
anomalous, cytologically benign tissue macrophages in a given site. In the
Hospital General y Universitario of Alicante, Spain, from 1975 to 1996 four
patients presented with granulomatosis and otorhinolaryngological signs and
symptoms: a 7-year-old girl with a right mastoid eosinophil granuloma, a 2-month
old boy with Letterer-Siwe syndrome whose illness started as acute mastoiditis, a
23-month-old boy who developed eosinophil granulomas of both mastoids and one
ischium, and an 8-month-old girl with a right zygomatico-temporal eosinophil
granuloma. The treatment and clinical course of each case is described and
compared with the results of other authors.
PMID- 9644867
TI - [Fungal sinusitis. Report of four cases].
AB - Fungal sinusitis has a nonspecific clinical presentation, is refractory to
standard medical treatment and may produce expansion and erosion of the sinus
wall. Various factors have been implicated in the development of fungal
sinusitis: anatomical factors in the osteomeatal complex, tissular hypoxia,
traumatic factors, massive exposure to fungal spores, allergy and
immunosuppression. Our study of four cases diagnosed in the department included
the clinical, pathological, and radiological features of fungal sinusitis. Five
forms are described. Bacterial infection often occurs. The diagnosis of fungal
sinusitis requires a high level of clinical and pathological suspicion. Before
surgery, fungal sinusitis is suggested by the clinical and radiological features,
and is confirmed by histological study. Culture of the tissue sometimes leads to
identification of the fungus. Surgical removal of the infection is the main
treatment for every form of fungal sinusitis.
PMID- 9644868
TI - [Paranasal sinus chondrosarcoma. A case report].
AB - We report a case of chondrosarcoma of the nasal cavity and paranasal sinuses.
These cartilaginous tumors are rare in the head and neck. The treatment of choice
is surgery.
PMID- 9644869
TI - [Electromyographic study of pharyngeal soft palate paralysis or Vernet syndrome].
PMID- 9644870
TI - [Cervical cutaneous leishmaniasis].
AB - A case of cutaneous leishmaniasis that presented as a large cervical ulceration
is reported. The etiopathogenesis, clinical manifestations, diagnosis, and
treatment are reviewed. The visceral and mucocutaneous forms of the disease were
excluded from this study.
PMID- 9644871
TI - [Simplified videonystagmoscopy].
AB - Videonystagmoscopy visualizes nystagmus on a television monitor and records it on
video tape for later study, records, and reproduction. Early attempts date from
long ago, but the technique only recently has spread, since the development of
complex computerized equipment which, however, confines it to certain vestibular
exploration laboratories. In order for this technique to become more widely used,
simple equipment is needed, such as that described in this article. Our system
consists of a single infrared light minivideo camera that is attached to the left
eye using an eyeglass-mounting system that also occludes the right eye. The
examination method is routine. Our results show the following advantages over
electronystagmography: visualization of the rotary component, non-interference of
visual stimuli, mechanical and electronic stability, speed, and low cost. If
necessary, it can be complemented by electronystagmography and computer analysis.
PMID- 9644872
TI - [Chronic elevation of enzymes of pancreatic origin in asymptomatic patients].
AB - Chronic asymptomatic elevation of pancreatic enzymes is a well known entity
although little has been reported. In most cases chronic asymptomatic elevation
of amylase is due to a salival isoamylase increase or macroamylasemia. However,
we have studied 10 cases with an increase in amylases due to pancreatic
isoamylase and an increase in the remaining pancreatic enzymes which remained
elevated during the follow up period ranging from 2 to 60 months. The amylase
values ranged from 186 to 1,600; the lipase from 176 to 3,989, trypsin from 476
to 2,430 and pancreatic isoamylase from 122 to 1,263. In all patients CT and
echography were carried out, which discarded structural damage. Nonetheless, an
indirect test of pancreatic function presented unexplained pathologic values in 4
out of 10 patients. In conclusion, we suggest that chronic asymptomatic elevation
of pancreatic enzymes is of unknown etiology with no associated structural
pancreatic pathology demonstrable by the usual study methods.
PMID- 9644873
TI - [Endoscopic, histologic and morphometric evaluation of the gastric mucosa in
patients with osteoarthritis treated with piroxicam and zinc acexamate].
AB - Zinc acexamate (ZAM) is an antiulcer agent with antisecretory and
gastroprotective properties. The aim of this study was to evaluate endoscopically
and morphometrically the efficacy of ZAM in the prophylaxis of gastroduodenal
lesions induced by pyroxicam. Thirty nine patients from 30 to 70 years of age
diagnosed with osteoarthritis without lesions in the upper digestive tract on
basal endoscopy were studied. A randomized, double blind study was designed in
which the patients received 20 mg/day of pyroxicam together with 300 mg/day of
ZAM or placebo for 4 weeks. Clinical controls were undertaken on days 0, 14, 28
and endoscopic and histologic controls performed on days 0 and 28. The two groups
were homogeneous regarding basal parameters. Endoscopic grading of the
gastroduodenal lesions at the end of the study was lower in the group treated
with ZAM (p < 0.001). Ulcers were found in only 2 patients (one antral and one
duodenal) both of whom were in the placebo group (10.5%). Histologic scoring
following treatment demonstrated higher values in the placebo group (p < 0.001)
and scarce alterations with respect to base values in the group treated with ZAM.
Morphometric quantification showed lower cell densities in both groups at the
body level (p < 0.001). However, these did not vary in the antrum in the group
treated with ZAM but increased in the placebo group (p < 0.001) as an expression
of proliferative cell response to mucosal damage. At a single nightly dosis of
300 mg ZAM is effective in the prophylaxis of gastric and duodenal lesions
induced by pyroxicam.
PMID- 9644874
TI - [Resection as elective treatment of hilar cholangiocarcinoma (Klatskin tumor)].
AB - A retrospective analysis of our experience in the treatment of hiliary
cholangiocarcinoma or Klatskin tumor was performed with the aim of evaluating the
morbi-mortality and prognosis of its treatment to thereby determine the
usefulness of the different therapeutic options. From 1989 to 1997, 51 patients
diagnosed with hiliary cholangiocarcinoma were treated in our hospital. Surgery
was indicated in 16 with curative aims (group I) while palliative treatment with
percutaneous biliary drainage was indicated in 35 (group II). Biliary resection
was carried out in 8 patients being associated with hepatic resection in 4 (group
IA) and in 8 patients undergoing liver transplantation (group IB). Clinico
epidemiologic data and hospital stay were similar in all the groups. The
frequency of complications was similar in groups I and II although the frequency
of cholangitis (49%) in group II was noticeable. The percentage of readmissions
was also greater in group II (12 vs 46%, respectively; p = 0.03) with prosthesis
obstruction being the most frequent cause. Accumulated survival at 1, 2, and 3
years in group I was 84, 64 and 48% with a median survival of 33 months, while in
group II the median survival was of 6 months with no patient surviving more than
2 years (p = 0.0001). When groups IA and IB were compared, greater frequency of
complications in groups IA (100 vs 37%; p = 0.002), similar frequency of
readmissions (87 vs 75%; p = NS), median survival greater in group IB (12.5
months vs 48 months) and significantly higher actuarial survival in group IB (48%
in 2 years vs 83% to 2 years; p = 0.02) was observed. In conclusion, surgery is
the treatment of choice in hiliary cholangiocarcinoma whenever possible, given
the greater survival without a significant increase in morbimortality. Likewise,
we consider that liver transplantation is a useful option in the treatment of
patients with cholangiocarcinoma type IV of Bismuth.
PMID- 9644875
TI - [Endometriosis: an infrequent cause of colonic obstruction].
AB - Endometriosis localized in the intestinal wall is not an infrequent finding.
Diagnosis is difficult given the diverse symptomatology presented with unspecific
abdominal pain being the most common. Implantation of endometrial tissue in the
intestinal wall may involve the mucosa and present as rectorhagia, with
colonscopic exploration providing diagnosis by biopsy of the affected area. In
other cases this may only involve the intestinal wall producing very varied
symptomatology. Presentation as a picture of colon obstruction is little
reported. The main problem is its difficult differential diagnosis with neoplasm
which, in most cases, leads to surgery. A case of colon obstruction provoked by
implantation of endometrial tissue in the wall of the sigma which was surgically
resolved is herein presented.
PMID- 9644876
TI - [Hydatid cyst in the hepatic hilum causing a cavernous transformation in the
portal vein].
AB - Portal cavernomatosis consists in the substitution of the portal vein by many
fine, twisting venules leading to the liver. This phenomenon is produced as a
consequence of anterior thrombosis of the portal vein and is associated with
chronic pancreatitis, cancer of the pancreas, intraabdominal sepsis and
cholelithiasis. The symptomatology may be nul or present as obstructive jaundice
or portal hypertension. Diagnosis is made by Doppler echography. The treatment is
portal shunt when symptomatology is produced. In patients with cholelithiasis
requiring surgery, the shunt is advised prior to biliary surgery since
perioperative hemorrhage, if present, may be incoercible as in the case herein
described. We present a 84-year-old woman with portal cavernomatosis the etiology
of which was a hydatidic cyst located in the hepatic bifurcation and treated with
mebendazol 10 years previously. This etiology has not been previously reported.
PMID- 9644877
TI - [Abdominal pain and ascites as manifestations of hereditary angioneurotic edema].
AB - Hereditary angioneurotic edema (HAE) is an infrequent autosomal dominant disorder
characterized by a decrease in the levels or a dysfunction of the complement C1
inhibitor factor (C1 inh). The clinical presentation varies widely and involves
any area of the organism. Gastrointestinal involvement is usually as abdominal
pain and may be accompanied by ascites. De novo diagnosis of HAE with abdominal
pain and ascites as a form of presentation is difficult with differential
diagnosis with abdominal pain of unknown origin. The appearance of ascites is
rare with few cases reported in the literature. Both abdominal pain and ascites
disappear a few days after initiation of medical treatment. Occasionally
exploratory laparotomy has been required. A new case of abdominal pain and
ascites as manifestations of HAE is herein reported.
PMID- 9644878
TI - [A case of non Hodgkin Lymphoma in a patient with hepatic cirrhosis by the
hepatitis C virus].
AB - We present a case of non-Hodgkin's lymphoma of B cells in a patient with
cirrhosis by hepatitis C virus. Our patient presented scarce symptomatology
related with non-Hodgkin's lymphoma. A notable hyperbilirrubinaemia with
hypoalbuminaemia were the only features that allowed us to suspect the diagnosis.
The diagnostic was proved by necroscopic study. There are several factors
involved in the etiology of non-Hodgkin's lymphoma, including infectious agents.
Recent Italian studies have suggested an association between C virus infection
and non-Hodgkin's lymphoma. We have carried out a bibliographical revision of
this association to conclude that important geographical differencies must be
pointed out.
PMID- 9644879
TI - [Pregnancy and intestinal inflammatory disease].
PMID- 9644881
TI - [Enteral nutrition in gastrointestinal disease].
PMID- 9644880
TI - [Collagenous colitis].
PMID- 9644882
TI - [Topical nitroglycerin in the treatment of anal fissure].
PMID- 9644883
TI - [Gastric adenocarcinoma and kidney transplantation].
PMID- 9644884
TI - [The prevalence of hepatitis C virus infection].
PMID- 9644885
TI - [Symptomatic recurrent or episodic fever of unknown origin in adenocarcinoma of
the colon].
PMID- 9644886
TI - [Gastric carcinoma with squamous differentiation].
PMID- 9644887
TI - [Differences in pharmaceutical products of omeprazole].
PMID- 9644888
TI - [Differences in pharmaceutical products of omeprazole].
PMID- 9644889
TI - An adaptive backpropagation neural network for real-time ischemia episodes
detection: development and performance analysis using the European ST-T database.
AB - A supervised neural network (NN)-based algorithm was used for automated detection
of ischemic episodes resulting from ST segment elevation or depression. The
performance of the method was measured using the European ST-T database. In
particular, the performance was measured in terms of beat-by-beat ischemia
detection and in terms of the detection of ischemic episodes. The algorithm used
to train the NN was an adaptive backpropagation (BP) algorithm. This algorithm
drastically reduces training time (tenfold decrease in our case) when compared to
the classical BP algorithm. The recall phase of the NN is then extremely fast, a
fact that makes it appropriate for real-time detection of ischemic episodes. The
resulting NN is capable of detecting ischemia independent of the lead used. It
was found that the average ischemia episode detection sensitivity is 88.62% while
the ischemia duration sensitivity is 72.22%. The results show that NN can be used
in electrocardiogram (ECG) processing in cases where fast and reliable detection
of ischemic episodes is desired as in the case of critical care units (CCU's).
PMID- 9644890
TI - Spatial filtering and neocortical dynamics: estimates of EEG coherence.
AB - The spatial statistics of scalp electroencephalogram (EEG) are usually presented
as coherence in individual frequency bands. These coherences result both from
correlations among neocortical sources and volume conduction through the tissues
of the head. The scalp EEG is spatially low-pass filtered by the poorly
conducting skull, introducing artificial correlation between the electrodes. A
four concentric spheres (brain, CSF, skull, and scalp) model of the head and
stochastic field theory are used here to derive an analytic estimate of the
coherence at scalp electrodes due to volume conduction of uncorrelated source
activity, predicting that electrodes within 10-12 cm can appear correlated. The
surface Laplacian estimate of cortical surface potentials spatially bandpass
filters the scalp potentials reducing this artificial coherence due to volume
conduction. Examination of EEG data confirms that the coherence estimates from
raw scalp potentials and Laplacians are sensitive to different spatial bandwidths
and should be used in parallel in studies of neocortical dynamic function.
PMID- 9644891
TI - Differential characterization of neural sources with the bimodal truncated SVD
pseudo-inverse for EEG and MEG measurements.
AB - A method for obtaining a practical inverse for the distribution of neural
activity in the human cerebral cortex is developed for electric, magnetic, and
bimodal data to exploit their complementary aspects. Intracellular current is
represented by current dipoles uniformly distributed on two parallel sulci joined
by a gyrus. Linear systems of equations relate electric, magnetic, and bimodal
data to unknown dipole moments. The corresponding lead-field matrices are
characterized by singular value decomposition (SVD). The optimal reference
electrode location for electric data is chosen on the basis of the decay behavior
of the singular values. The singular values of these matrices show better decay
behavior with increasing number of measurements, however, that property is useful
depending on the noise in the measurements. The truncated SVD pseudo-inverse is
used to control noise artifacts in the reconstructed images. Simulations for
single-dipole sources at different depths reveal the relative contributions of
electric and magnetic measures. For realistic noise levels the performance of
both unimodal and bimodal systems do not improve with an increase in the number
of measurements beyond approximately 100. Bimodal image reconstructions are
generally superior to unimodal ones in finding the center of activity.
PMID- 9644892
TI - Adaptive canceling of physiological tremor for improved precision in
microsurgery.
AB - Physiological hand tremor impedes microsurgery. We present both a novel adaptive
algorithm for tremor estimation and a new technique for active real-time
canceling of physiological tremor. Tremor is modeled online using the weighted
frequency Fourier linear combiner (WFLC). This adaptive algorithm models tremor
as a modulating sinusoid, and tracks its frequency, amplitude, and phase.
Piezoelectric actuators move the surgical instrument tip in opposition to the
motion of tremor, effectively subtracting the tremor from the total motion. We
demonstrate the technique in one dimension using a cantilever apparatus as a
benchtop simulation of the surgical instrument. Actual hand motion, prerecorded
during simulated surgery, is used as input. In 25 tests, WFLC tremor compensation
reduces the rms tip motion in the 6-16 Hz tremor band by 67%, and reduces the rms
error with respect to an a posteriori estimate of voluntary motion by 30%. The
technique can be implemented in a hand-held microsurgical instrument.
PMID- 9644893
TI - Simulation of depolarization in a membrane-equations-based model of the
anisotropic ventricle.
AB - The results of a simulation study of the propagation of depolarization in
inhomogeneous anisotropic (monodomain) myocardial tissue are presented.
Simulations are based on modified Beeler-Reuter membrane equations, and performed
on a block of anisotropic myocardium with rotating fiber geometry, measuring 1 cm
x 1 cm x 0.3 cm, at various levels of spatial discretization (0.15 mm, 0.30 mm,
0.60 mm). At a discretization level of 0.6 mm the algorithm allowed the
simulation in a realistically shaped model of the ventricle, including rotational
anisotropy, as well. For this simulation results are justified by comparing
results for the block at various levels of discretization, for which the surface
to volume ratio has been adjusted. By placing the model ventricle in a
realistically shaped (human) volume conductor model, realistic body surface
potentials (QRST waveforms) are simulated.
PMID- 9644894
TI - Biological cells with gap junctions in low-frequency electric fields.
AB - Biological effects have been observed from weak, low-frequency magnetic fields.
It has been suggested that the observed effects are due to the induced currents
and electric fields. The behavior of cells exposed to an electric field is
investigated in this paper. The induced transmembrane potential (TMP) is examined
in geometrically complex models of various cell configurations. The TMP is
evaluated using the finite element method (FEM), a numerical technique that is
well suited to complicated geometries. Because displacement currents can be
neglected at very low frequencies, a FEM solver that considers only material
conductivity is used. Therefore, our results apply only well below the relaxation
frequency. Chains and clusters of gap-connected cells of various sizes are
modeled. The conductivity and size of the gap junctions in the cell
configurations are also varied. The results for small configurations are compared
to models of ellipsoidal cells with shapes similar to those of the
configurations. FEM estimates of TMP's in long, cylindrical cell chains are
compared to the predictions of the leaky cable model. The FEM approach confirms
that gap-junction-connected cells can be treated as a single similarly shaped
cell. Gaps influence the potential in the interior of cell configurations, and
these effects increase with gap size and conductivity. For configurations to
which approximations such as the leaky cable model do not apply, the FEM approach
can be used to estimate the TMP, if the model is adapted to fit within
computational memory limits.
PMID- 9644895
TI - A study of printed spiral coils for neuroprosthetic transcranial telemetry
applications.
AB - We have explored the use of printed spiral coils (PSC's) for neuroprosthetic
transcranial telemetry applications. We fabricated two-dimensional PSC's on a
thin (25 microns) polyimide substrate using copper (35 microns) as a conducting
material. All the coils had a fixed inner diameter of 1.0 cm. We fabricated two
sets of coils. One set of coils consisted of 2- to 5-turn circular and square
spiral coils and had different trace widths (W), different spacings (S) between
adjacent traces, and different outer diameters. The other set of coils consisted
of 5-turn circular spiral coils and had fixed inner and outer diameters but
different W to S ratios. We measured loss resistances (Rs and Rp) and quality
factors (Q) of these coils at different resonating frequencies in the range of 5
40 MHz. Over this frequency range, we observed that for fixed inner and outer
diameters, the coil with the largest W achieved the lowest Rs and the highest Rp
and Q. These electrical properties and the fact that these coils can conform to
the complex convoluted cortical surface suggest that a PSC [15] can provide a
viable alternative to a conventional wire-wound coil for neuroprosthetic
transcranial telemetry applications.
PMID- 9644896
TI - Geometric effects on resistivity measurements with four-electrode probes in
isotropic and anisotropic tissues.
AB - We studied via computer simulation the effects of electrode diameter, electrode
length, interelectrode spacing, and tissue size on the accuracy of measured
tissue resistivities and anisotropy ratios obtained with the widely used four
electrode technique. Such measurements commonly assume an ideal situation in
which the four electrodes are infinitesimally small and the tissue is semi
infinite. Our study shows that these geometric factors can significantly affect
measured resistivities, particularly for anisotropic tissues. The measured
anisotropy ratio is decreased by either 1) increasing the electrode diameter or
length relative to the interelectrode spacing of the probe or 2) decreasing
tissue size. We have provided an equation for estimating errors in the measured
anisotropy ratio from the parameters of electrode and tissue geometries. The
simulation findings are supported by our in vitro experimental results.
PMID- 9644897
TI - Microwave catheter design.
AB - A microwave antenna system for transcatheter ablation of cardiac tissue is
investigated. A numerical model based on the finite-difference time-domain method
incorporating a Gaussian pulse excitation has been constructed and frequency
domain electric and magnetic fields are obtained through Fourier transformation.
Results are presented for a coaxial line fed monopole catheter which is modified
by the successive inclusion of a Teflon sheath outer coating, a terminating disk
at the tip of the antenna, a sleeve choke, and a high dielectric constant
cylinder surrounding the monopole antenna. The effects of these design features
are characterized in terms of specific absorption rate (SAR) and return loss
(RL). Numerical calculations are confirmed by comparing with the RL measurement
of a Teflon-coated monopole containing a disk and choke.
PMID- 9644898
TI - Microfabricated cantilevers for measurement of subcellular and molecular forces.
AB - We present two new microfabricated cantilever-beam force transducers. The
transducers were fabricated from thin silicon-nitride films, and were used
respectively to measure forces generated by two small-muscle preparations: the
single myofibril, and the single actin filament in contact with a myosin-coated
surface. A simple resonance method was developed to characterize the transducers.
Because of the high reproducibility of lever dimensions and the consistency of
the modulus of elasticity, few calibration measurements sufficed to characterize
the stiffness of all the levers on a single wafer.
PMID- 9644899
TI - An iterative Newton-Raphson method to solve the inverse admittivity problem.
AB - By applying electrical currents to the exterior of a body using electrodes and
measuring the voltages developed on these electrodes, it is possible to
reconstruct the electrical properties inside the body. This technique is known as
electrical impedance tomography. The problem is nonlinear and ill conditioned
meaning that a large perturbation in the electrical properties far away from the
electrodes produces a small voltage change on the boundary of the body. This
paper describes an iterative reconstruction algorithm that yields approximate
solutions of the inverse admittivity problem in two dimensions. By performing
multiple iterations, errors in the conductivity and permittivity reconstructions
that result from a linearized solution to the problem are decreased. A finite
element forward-solver, which predicts voltages on the boundary of the body given
knowledge of the applied current on the boundary and the electrical properties
within the body, is required at each step of the reconstruction algorithm.
Reconstructions generated from numerical data are presented that demonstrate the
capabilities of this algorithm.
PMID- 9644900
TI - Optimization of the deposited power distribution inside a layered lossy medium
irradiated by a coupled system of concentrically placed waveguide applicators.
AB - A method is proposed for controlling the deposited power distribution in a
layered cylindrical lossy model, irradiated by a phased-array hyperthermia system
consisting of four waveguide applicators. A rigorous electromagnetic model of the
heated tissue, which takes into account coupling phenomena between system
elements, is used for predicting the electric field at any point inside tissue.
The relative amplitudes and relative phases of the array elements are optimized
in order to attain desired specific absorption rate (SAR) distributions inside
and outside malignant tissues. A constrained nonlinear optimization problem is
solved by using the penalty function method and the resulting unconstrained
minimization of the penalty function is carried out by the downhill simplex
method. Two practical phased-array hyperthermia systems have been studied and
numerical results are presented.
PMID- 9644902
TI - Multipolar laminated electromagnet for low-field magnetic resonance imaging and
electron paramagnetic resonance imaging.
AB - A cylindrical 16-pole electromagnet (EM) for electron paramagnetic resonance
imaging (EPRI) and low-field magnetic resonance imaging (MRI) has been designed
by means of two-dimensional and three-dimensional (3-D) finite element analysis
(FEA). The use of an automatic procedure that combines FEA with a minimization
routine allowed the optimization of the design, in order to improve the
homogeneity along the axis of the EM. A prototype has been built by using
electrical steel sheets that were cut by laser; this solution reduced
significantly the manufacturing cost. The EM operates with a maximum flux
density, in the bore, of 0.08 T and has a homogeneity along the axis of about 40
parts per million (ppm) in a spherical region 10 cm in diameter. It generates the
main field and two of the three field gradients required in the 3-D image
reconstruction. Good agreement was found between the results of simulation and
the measured values.
PMID- 9644901
TI - Measuring the progression of foreign-body reaction to silicone implants using in
vivo MR microscopy.
AB - We used in vivo magnetic resonance (MR) microscopy to follow the growth of
fibrous capsule as a foreign body reaction to silicone implants in rats.
Anesthetized rats were imaged 1, 7, 14, and 28 days after silicone-coated MR
imaging coils were sutured to their neck muscles. On the twenty-eighth day, rats
were sacrificed and coils and adjacent tissues were removed en bloc and fixed in
formalin, reimaged with MR, and sectioned for conventional histology. Three
dimensional (3-D) spin-echo [3DFT] acquisition gave in-plane resolution of 32 x
32 microns in vivo and 16 x 16 microns ex vivo. All MR images showed a diffuse
band of elevated signal intensity between the silicone of the coil and adjacent
tissue. The border of the hyperintense band was thin and not well defined at
seven days post-implantation. From 7-28 days, the band showed relatively
homogeneous signal intensity and its thickness increased 44% on the rectus muscle
side and 78% on the subcutaneous side. The capsule thickness determined either by
MR in vivo and ex vivo microscopy or conventional histology was not significantly
different, and there was a significant correlation between thickness measurements
among those methods. MR in vivo microscopy provides sufficient resolution and
spatial information to serially evaluate the growth of the foreign body fibrous
capsule over time, thus achieving greater accuracy and consistency in
measurements.
PMID- 9644903
TI - A comparative study of human skin thermal response to sapphire contact and
cryogen spray cooling.
AB - Surface cooling, in conjunction with various thermally mediated therapeutic
procedures, can provide a means to protect superficial tissues from injury while
achieving destruction of deeper targeted structures. We have investigated the
thermal response of in-vivo human skin to: 1) contact cooling with a sapphire
window (6-12 degrees C); and 2) spray cooling with a freon substitute cryogen
[tetrafluoroethane; boiling point approximately -26 degrees C at 1 atmospheric
pressure (atm)]. Measurements utilizing infrared radiometry show surface
temperature reductions from 30 degrees C to 14-19 degrees C are obtained within
approximately 1 s in response to sapphire contact cooling. Surface temperature
reductions to values between 5 degrees C and -9 degrees C are obtained in
response to 20-100-ms cryogen spurts. Computational results, based on fitting the
measured radiometric surface temperature to estimate heat transfer parameters,
show: 1) temperature reductions remain localized to approximately 200 microns of
superficial tissue; and 2) values of heat flux and total energy removed per unit
skin surface area at least doubled when using cryogen spray cooling.
PMID- 9644904
TI - KLT-based quality controlled compression of single-lead ECG.
AB - An electrocardiogram (ECG) compression algorithm based on a combination of the
Karhunen-Loeve transform (KLT) and multirate sampling is introduced. The use of
multirate sampling reduces KLT computational times to those reported for wavelet
packet-based compression techniques. A beat-by-beat quality controlled
compression criterion is shown to be necessary to ensure clinically adequate
reconstruction of each beat. The resulting quality controlled algorithm
efficiently achieves compression rates of approximately 30-40:1 for the MIT-BIH
database.
PMID- 9644905
TI - A simple design methodology for elliptical cross-section, transverse, asymmetric,
head gradient coils for MRI.
AB - A simple design process for the design of elliptical cross-section, transverse
gradient coils for use in magnetic resonance imaging (MRI) is presented. This
process is based on a flexible stochastic optimization method and results in
designs of high linearity and efficiency with low switching times. A design study
of a shielded, transverse asymmetric elliptical coil set for use in neural
imaging is presented and includes the minimization of the torques experienced by
the gradient set.
PMID- 9644906
TI - [Heat barriers in progressive evolution of animals and humans].
AB - The principle of fastest descent in thermodynamics of nonequilbrium processes is
a physical foundation of progressive evolution of animals and humans. We present
a curve of bioenergetic progress of animals and demonstrate that movement along
this curve form a certain moment is only possible if "the first heat barrier" is
overcome, which corresponds to the intensity of animal respiration (coefficient a
5-6 mWt/g). Overcoming this barrier is related to the development of
thermoregulation and appearance of homoiothermic animals. "The second heat
barrier" (coefficient a about 45-50 mWt/g) is related to heating of the animal
body up to the damaging temperatures and this barrier is overcome as a result of
conscious activity and the appearance of human civilization. The possibility of
"the third heat barrier" is discussed as a result of energy production by
industry. Overcoming of "the third heat barrier" is possible through assimilation
of the space and transfer in the space of energy-producing industry.
PMID- 9644907
TI - [The nature of the circahoralian (ultradian) intracellular rhythms. Similarity to
fractals].
AB - The properties and possible origin of circahoralian intracellular rhythms are
discussed. Irregularity of these oscillations, as expressed in different time
scales, determination, and resistance to external influences, including changes
in the environmental temperature, are noted. No pacemaker of circahoralian
rhythms was found. These specific features and analysis of the structure of
circahoralian rhythms (Herst equation) suggest their similarity to fractals,
chaotic but determined forms with a certain internal structure. Determination of
circahoralian rhythms in a cell-free system and their possible fractal nature
characterizes the rhythms as an imminent property of the cytoplasm, that does not
require special regulation. Modulations of the frequency and amplitude of
oscillation under the influence of external influences are described. It is
proposed that the circahoralian rhythms are a protective factor for the cell and
organ functions and a mechanism of adaptations under varying life conditions.
PMID- 9644908
TI - [Regulation of myogenesis].
AB - Molecular-biological and molecular-genetic mechanisms underlying regulation of
muscle formation were analyzed from the earliest stages of commitment and
determination of myogenic precursors to the terminal stages of muscle
differentiation. It was shown how inductive influences of the neural tube and
notochord on the somites leading to formation of myotomes are related to
expression of genes of the Shh and Wnt families. Differentiation of proliferating
myoblasts and myotubes is related to expression of the genes encoding synthesis
of bHLH proteins: MyoD and Myf5 in the myoblasts and myogenin and MRF4 in the
myotubes. The products of these genes are transcription factors and control the
subsequent stages of myogenesis, specifically, myogenin controls expression of
the genes of contractile proteins. Changes in the spectra of contractile proteins
during ontogenesis and diversity of their isoforms are related both to the
expression of various genes and to their alternative splicing. The mechanisms
underlying the assembly of myofibrils in ontogenesis, which involve, in addition
to myosin and actin, proteins of Z-bands and A-discs, were analyzed.
PMID- 9644909
TI - [Flocculation of bacterial cells in culture with protozoa].
AB - The initial phase of formation of the biogenic suspension was studied in
experimental communities of bacteria and protozoans that simulate degradation of
the phenol technogenic flows. Protozoans were shown to initiate formation of
bacterial aggregates and increase the size of bacterial flocules several hundred
times. Factors were found by the methods of mathematical planning, which markedly
affect the size and amount of flocules. Unlike natural water bodies, in the
sample communities, the presence of abiogenic substrate was not essential for
aggregation of the bacteria. The aggregated bacterial cells make an important
contribution to degradation of organic compounds.
PMID- 9644910
TI - [Response of adult djungarian hamsters (Phodopus sungorus) to odor signals of
species of their own and opposite sex during different seasons with the reference
to reproduction process].
AB - Studies were carried out on adult Djungarian hamster (Phodopus sungorus) males
living in familial pairs under natural thermal and light regimes year-round. The
response of hamsters to the odors of urine, secretory substances of the
midabdominal gland and additional saccules in the ostium of cheek pouches, and
faeces from conspecific males and females were studied. The results obtained
suggest that the odors of urine and also feces play an important role in sexual
recognition of individuals. These odors are especially attractive for the males
in summer, during the period of active breeding. The tested males examined the
odor of the midabdominal gland from individuals of the same sex reliably longer
throughout the year, but in winter the interest in this odor was higher than in
summer. These secretory substances appear to be important in organization of
territorial interactions between individuals. The results of observations on
breeding and the data on sex ratio in the broods from pairs with the tested males
were compared to similar data obtained earlier for Roborovskii hamsters (Sokolov
and Feoktistova, 1996). Similarities and differences were found in the course of
breeding in the studied species.
PMID- 9644911
TI - [Strategy of small rodent populations from Kanev national park under habitat
changes caused by technogenic pollutions and an accident at the Chernobyl nuclear
power station].
AB - The results of a long-term investigation are provided, which permit us to
evaluate the problem of population adaptation to qualitative habitat changes due
to the accident at the Chernobyl nuclear power station from a new standpoint. We
note the specific response of various species, the disturbed ecological balance,
and a slowing of the "population clock" and biotic cycle.
PMID- 9644912
TI - [Anticoagulant and fibrinolytic effects of proline-containing peptides].
AB - Anticoagulant, fibrinolytic, and fibrin-depolymerization effects were revealed
during in vitro study of five proline-containing peptides (Gly-Pro, Trp-Pro, Pro
Gly, Gly-Pro-Gly-Gly, and Pro-Gly-Pro) in the concentration range 10(-9) to 10(
1) mg/ml. Intravenous injection of Trp-Pro and Pro-Gly into white rats at 250
micrograms/kg body weight significantly increased recalcification time and
activated partial thromboplastin time of serum coagulation, increased
fibrinolytic activity, decreased the level of serum factor XIII/(/)a and
fibrinogen, and reduced thrombocyte aggregation. We propose inhibition of
thromboplastin and thrombin formation in the serum by the studied proline
containing peptides both in vitro and in vivo.
PMID- 9644913
TI - [Response of the isolated muscle tissue of frog species to the successive effects
of subtoxic and toxic chloral hydrate solutions].
AB - Time-related changes in the mean resistance of sartorius muscle from individual
common frogs to the toxic effect of chloral hydrate (0.05 and 0.08 M) were
observed. The correlation coefficient between the initial muscle resistance and
the value and direction of its changes as well as between the resistance of the
paired muscle under the influence of subtoxic chloral hydrate solution (0.005 M)
was calculated. A biphase pattern of change of almost all the above indices
depending on the dose of pretreatment was observed. Time-related changes in the
correlation coefficient between muscle resistance and its changes and between the
resistance of the paired muscle and variability of the resistance proved to be
much more informative than the mean resistance concerning both the muscle
response to the stimulus and functional state of the muscle cells.
PMID- 9644914
TI - [Study of amphibian brain asymmetry during normal embryonic and larval
development].
AB - Amphibian embryos (Triturus vulgaris, Pleurodeles waltl, Hynobius keyserlingii,
Ambystoma mexicanum, Rana temporaria, Bufo bufo, and Xenopus laevis) were
investigated. We ascertained the morphological right-side asymmetry of the brain,
which appears at the neurula stage and is preserved during the postembryonic
(larval) development. In T. vulgaris, P. waltl, H. keyserlingii, and X. laevis,
we observed right-side asymmetry of peripheral analyzers, such as the retina,
ganglia of nerve VIII, and olfactory placodes. Structural analysis of the
forebrain in A. mexicanum has shown that in the larvae, the pallium prevails on
the left side of the cerebral hemisphere. During metamorphosis, left-side
asymmetry is replaced by right-side, which is then preserved. We propose that the
brain asymmetry arose at the early stages of evolution as a result of embryonic
formation of the nervous system.
PMID- 9644915
TI - [Pathogenesis and laboratory diagnosis of diabetic nephropathy (literature
review)].
PMID- 9644916
TI - [Evaluation of the reserve potential of the blood kallikrein-kinin system in
healthy subjects].
AB - The reserve potential of the blood kinin-producing activity and kallikrein
inhibitors were assessed under conditions of a functional test (double local
hypoxia of the upper limb) in 68 healthy volunteers aged 17-45 years. Three types
of reactions of the studied components of the kallikrein-kinin system (KKS) were
distinguished: concomitant (79.4%), kininase (5.9%), and kininogenesis (14.7%).
The concomitant type was characterized by increased activity of all components of
the system during the test, indicating its sufficient reserve potential. A drop
of kinin production and increased activity of the inhibitory component of KKS in
response to hypoxia reflect a low reserve potential of kininogenesis in subjects
with the kininase type of KKS. An appreciable decrease of kallikrein inhibitor
activity during the test in the presence of increased kininogenesis demonstrates
the limited reserves of the inhibitory component of the kinin cascade in normal
subjects with the kininogenesis type of KKS.
PMID- 9644917
TI - [Laboratory criteria of ejaculate fertility (literature review)].
PMID- 9644918
TI - [The effect of laser radiation on the seminal fluid in man].
AB - The effect of low-intensive laser with a wavelength of 0.63 micron on human
seminal fluid is studied. Seminal fluids of different groups distinguished
according to spermogram values differently react to laser exposure. Experimental
studies demonstrated both stimulating and destructive effects of laser on human
seminal fluid.
PMID- 9644919
TI - [Differential diagnosis of hematuria on the basis of morphology of stained
erythrocytes].
AB - Glomerular and nonglomerular hematuria was differentiated in 40 patients by the
morphology of erythrocytes stained with floxin in buffer solution. Glomerular
hematuria was correctly diagnosed in 91.0%, nonglomerular in 88.9% of patients.
The results of diagnosis of hematuria by floxin staining and by phase-contrast
microscopy coincided; both methods are superior to the Right staining technique.
The proposed method is easily available for any laboratory and is suggested for
tentative diagnosis, in order to improve the diagnostic process.
PMID- 9644920
TI - [Detection of chlamydial infection by indirect cytological signs].
AB - The author compares the efficacy of detecting chlamydial infection by the
following methods: morphocytological analysis of urogenital smears under light
microscope by indirect signs, such as 1) neutrophil histiocyte macrophagal
reaction; 2) lymphoid infiltration with the presence of young forms; 3) basal
cell hyperactivity with dysplasia; 4) proliferation of the cylindrical epithelium
with dysplasia, and 5) dystrophic changes in the epithelium; detection of
chlamydial antigen by immunofluorescence and enzyme immunoassay; and detection of
specific antibodies. A total of 240 patients were examined at the Regional Family
Planning Center (163 women and 43 men of fertile age and 34 children and
adolescents). Chlamydial origin of inflammation suspected from the above
cytomorphological signs in 208 (87%) patients was confirmed by virological
studies: chlamydial antigen was detected in 67% and specific antibodies in
diagnostic titers in 20% of patients. This latter group was administered a course
of specific antichlamydial therapy after detection of chlamydial antigen. The
author concludes that patients with morphocytological signs of chronic
inflammation listed above detected in the urogenital smears should be referred to
a group at risk of chlamydiasis. The proposed method of screening is rapid,
economic, and easily available.
PMID- 9644921
TI - [Adhesiveness of peripheral blood neutrophils in normal subjects and in cancer
patients].
AB - A spectrophotometric method for assessing the capacity of phagocytes to adhere to
the plastic is proposed. The method consists in staining a cell monolayer after
Romanovsky-Giemsa in the wells of a 96-well flat-bottom plate, extraction of the
stain, and assessment of the optic density of this solution at 650 nm. Methods
for obtaining the cells in leukocyte concentrate (LC) and neutrophil suspension
(NS) obtained in the density gradient are described. Two calibration curves for
LC and NS are plotted for assessing the correspondence between optic density and
a certain number of adhesive neutrophils. There were no statistical differences
between the two curves. Neutrophil adhesion parameters of 38 donors are
presented. The adhesive capacity of blood neutrophils is decreased in cancer
patients (in 25 out of 27).
PMID- 9644922
TI - [Cytological diagnosis of thyroid cancer in a child using puncture biopsy of the
cervical lymph node].
PMID- 9644923
TI - [Osteoporosis: diagnosis of disorders of bone tissue and calcium-phosphorus
metabolism (lecture)].
AB - Tentative diagnoses of lymphadenitis or Hodgkin's disease were not confirmed in a
12-year-old child by cytological investigations. Along with lymphoid cells,
individual leukocytes, histiocytes, macrophages, and glandular cancer cells, the
cytological preparation of the cervical lymph node biopsy specimen contained
uncommon multinuclear cells looking like interfollicular thyroid islets. This
indicated cancer metastasis and the site of primary involvement: the thyroid. The
diagnosis was confirmed by the histological and radionuclide methods.
PMID- 9644924
TI - [Statistical estimation of the precision of clinico-laboratory measurements].
AB - Traditionally, the term "precision" denotes the quality of work, uniting the
correctness and reproducibility of results. However, it can have another sense:
the minimal difference between the specimens, detectable by this or that device
or method. In order to rule out misunderstanding, we propose to use the term
"measuring precision", if the term is used in its second meaning. It is easy to
assess the measuring precision by statistical processing of large scope of data:
if the histogram shows waves which disappear after the histogram step is
increased, this means that the device and method used in this study permit
biochemical analysis only at measuring precision corresponding to the histogram
step at which the waves disappear. A table of measuring precision values is
offered for 19 methods realized using the Labsystems FP-900 device (Finland) In
many cases it is obviously low.
PMID- 9644925
TI - [Characteristics of the organization of clinical laboratory using modern
hematological analyzers].
AB - Large treatment and prophylaxis multiprofile centers should be equipped with
several devices with different potentials. Rational use of the potentials of
modern hematological analyzers requires use of venous blood samples. Complete
hematological analyzers, such as Cobas Vega, can minimize visual assessment of
the leukocytic formula. Effective clinical application of the entire complex of
parameters offered by the analyzers and introduction of these devices in practice
involve upgrading of all laboratory workers.
PMID- 9644926
TI - [MEDLAB-97 (12th European Congress on Clinical Chemistry. Basel, Switzerland)].
PMID- 9644927
TI - [Prions and neurodegenerative human diseases].
PMID- 9644928
TI - [Role of molecular mechanisms regulating functions of glucocorticoid hormone
receptors in pathogenesis and treatment of cardiovascular diseases].
PMID- 9644929
TI - [New opportunities in diagnosis and treatment of gastroesophageal reflux and
cardial achalasia (dedicated to 65th anniversary of professor A.L. Grebnev)].
PMID- 9644930
TI - [Problems of osteoporosis: study of biochemical markers of bone metabolism].
PMID- 9644931
TI - [Efficacy of ursodeoxycholic acid (UDCA) in the treatment of chronic alcoholic
hepatitis].
AB - Treatment for chronic alcoholic hepatitis with UDCA drug was performed in 76
patients. In development of this kind of hepatitis an essential role belongs to
defects in the systems of lipid peroxidation and antioxidant defense. The UDCA
drug produced stabilization of cell membranes, changed bile composition by
effects on bile acids pool and micellar complex. Clinicomorphological remission
was available in 88% of cases.
PMID- 9644932
TI - [Pericarditis: 5 year records of general hospital].
AB - Among patients admitted to the therapeutic department of the general hospital for
5 years, diagnosis of pericarditis was made in 110 patients (0.44%). Among the
most common causes of secondary pericarditis were: chronic renal failure (31.8%),
diffuse lesion of the connective tissue (17.7%), tumor metastases to the
pericardium (15.5%). Primary pericarditis was, as a rule, of tuberculous
etiology. Morphologically, it was adhesive or adhesive-exudative, constrictive,
exudative in 13, 4.5 and 76% of patients, respectively. Half of the patients with
exudative pericarditis had 300 to 800 ml of fluid in the pericardial cavity.
Typical clinical manifestations were dyspnea and tachycardia. X-ray was
diagnostically valuable in pericardial exudate 300 ml and more. ECG voltage fell
in exudate more than 400-500 ml. Echocardiography remains an effective tool in
diagnosis of pericarditis. The treatment consisted of antibiotics,
antiinflammatory therapy, evacuation of the liquid from the pericardial cavity.
PMID- 9644933
TI - [Differential diagnosis of neurocirculatory asthenia (NCA)].
AB - 170 patients with primary diagnosis of NCA underwent detailed examination by the
therapist, neuropathologist, endocrinologist, urologist, gynecologist and
psychiatrist. Primary diagnosis was confirmed only in 47 patients, the other 123
patients had different somatic, neurological or psychic disorders. These 47 and
123 patients were considered as having NCA as a syndrome and as an independent
nosological entity, respectively. NCA as a syndrome was associated with blood
hypertension, nervous asthenia, ischemic heart disease, spinal osteochondrosis.
One third of the patients had neuropsychic disorders. The conclusion is made that
all the NCA patients require detailed therapeutic, neurological and psychic
examinations to exclude hypertension, asthenoneurotic states, ischemic heart
disease and spinal osteochondrosis.
PMID- 9644934
TI - [Seasonal changes of secondary immunodeficiency in patients with vascular
dystonia].
AB - The examination of 60 patients with vascular dystonia (VD) and immunological
disorders shows that secondary immunodeficiency is not a stable condition. It is
associated with seasons of the year and VD variants. Secondary immunodeficiency
is more pronounced in winter. A correlation exists between mixed vegetative
vascular dystonia and combined T-lymphocyte secondary immunodeficiency in winter.
The findings may help in planning immunotherapy in "critical seasons" for
patients with vegetative disorders.
PMID- 9644935
TI - [Nimotop: clinical spectrum].
AB - This literature review concerns both well known facts on mechanisms of action of
calcium channels blockers and less known effects on different systems of the
body. In addition to vascular dilatation, the blockers produce neuroprotective
action, promote dysaggregation. Detailed information is given on usage of soluble
calcium antagonist-nimotop.
PMID- 9644937
TI - [Noninvasive monitoring of arterial pressure in diagnosis and treatment of
arterial hypertension].
PMID- 9644939
TI - [Problem of heart insufficiency in the XIX European Cardiology Congress
(Stockholm, August 1997)].
PMID- 9644938
TI - [Crohn's disease of stomach].
PMID- 9644940
TI - [International Chronobiology Congress].
PMID- 9644941
TI - [The art of lecturing clinical medicine. Communication 1. Role of clinical
lecture in physician's training].
PMID- 9644942
TI - [Classification of chronic gastritis designed in Huston and its differences from
sydney system].
PMID- 9644943
TI - [Austrian reforms of university medical education in the second half of XVIII
century. Communication 1. H.Van-Sviten's reforms of education at Vien university
medical department].
PMID- 9644944
TI - [Pharmacological modulation of the appetite].
AB - The hypothalamus plays an essential role in the regulation of the body weight of
all living creatures. In it there is a convergence of signals from the nervous
system and signals from the peripheral tissues, through a complex system of
neurotransmitters and neuropeptides. The ever increasing understanding of this
field, opens up new therapeutic possibilities, both current and future, in the
treatment of eating disorders.
PMID- 9644945
TI - [L-carnitine levels in critical septic patients receiving parenteral nutrition].
AB - Septicemia causes multiple and often not very well understood metabolic
alterations. In this sense it is controversial whether or not carnitine is
decreased, which may have several implications. Our objective is to measure the
plasma carnitine levels in septicemic patients, and to find out whether this is
modified if there is a multi-organ dysfunction syndrome (MODS), or if it is
dependent on the lipid source. For this we carried out a prospective study in
septicemic patients with MODS. These were given exclusively parenteral nutrition
(PN) without any carnitine supplementation. The PN of 16 patients contained long
chain triglycerides (LCT's), while that of another 12 contained a 1:1 mixture of
long and medium chain triglycerides (LCT's and MCT's). We measured the plasma
carnitine level at the baseline, after 5 days and after 10 days, using an
enzymatic method that measures the total carnitine level (free and esterified).
The normal values lie between 35 and 70 mumol/l. We included 28 septicemic
patients whose ages were 53.41 +/- 16.51 years, and whose APACHE II on admission
was 17 +/- 4. The carnitine levels were: baseline: 60.4 +/- 23.7; 5th day 57.7 +/
22.9; 10th day 55.7 +/- 21.2 (p = n.s.). Of these patients, 10 had an MODS of
septic origins with their baseline levels being: 65.3 +/- 30.9; 5th day 60.3 +/-
23.2; 10th day 61.5 +/- 15.5; while the levels of the 18 septicemic patients
without MODS, the baseline levels were 61.9 +/- 13.8; 5th day 58.6 +/- 19.1; 10th
day 56.6 +/- 19.3 (p = n.s.). In the patients who were given LCT's the baseline
carnitine level was 60.7 +/- 23.1, 5th day 60.1 +/- 23.8; 10th day 58.6 +/- 12.8;
while those patients who were given LCT/MCT showed baseline levels of 64.3 +/-
19.5; 5th day 58.6 +/- 19.1; 10th day 57.8 +/- 10.7 (p = n.s.). In our septicemic
patients the serum carnitine levels we found were within the normal range, and
these remained unchanged during the ten days in those patients with MODS or with
the lipid mixture used.
PMID- 9644946
TI - [Nutritional state of iron in the institutionalized aged: study of intake and
hematological indices].
AB - In this study we determined the nutritional state of iron in 93 elderly people
who were institutionalized in Granada, by means of a determination of their
ingested iron, as well as the determination of the serum iron, hematologic
parameters (hemoglobin and hematocrit), and the corpuscular indexes (mean
corpuscular volume and mean corpuscular hemoglobin). The elderly people had an
iron intake that was considered to be adequate (10.2 +/- 2.1 mg/day), and this is
not related to the hematological parameters studied. 4% of the men, and 22% of
the women showed hemoglobin values that were considered to be low.
PMID- 9644947
TI - [Weight and height of school children from the L'Horta region (Valencia)].
AB - The growth and development of Valencian children from 6 to 14 years of age was
studied using the weight and height of a representative sample (n = 2011) of
school children in L'Horta de Valencia area. They represent 62% and 32.5% of the
school population of the Valencia province and of the Comunidad Valenciana,
respectively. The sample was proportional to the whole population in the
geographical area and to sex and age. The measured children came from 10 schools,
some of which were public and some private, drawn at random. After obtaining the
permission from the school administrative board the measurements were taken,
always by the same trained anthropometrist and with the same instruments, which
were calibrated daily. The application of the Lilliefors test showed that the
distribution of weight and height according to age was normal in the majority of
the groups of age. Therefore, the Student t-test was applied to compare girls and
boys, and given the fact that the symmetry was not complete in all age ranges,
the results are expressed as percentiles. From 6 to 14 years girls and boys in
Valencia show a similar weight evolution. Only in children in the highest
percentiles, can be observed sex-related differences from the age of 12 on. In
general, up to 13-14 years of age boys were slightly taller than girls of the
same age. From this age on boys follow continue growing while girls stop their
longitudinal growth.
PMID- 9644948
TI - [Changes in feeding behavior of patients who had received enteral nutrition
during the 1st year of life].
AB - Enteral feedings delivered by either gastrostomy or a nasogastric tube are often
used in infants and toddlers to ensure adequate caloric and nutrient intake. If
we are not aware of a rapid introduction of oral feedings they may develop poor
feeding skills. PATIENTS: Seven infants (mean age: 6.7 months; SD: 3.6) presented
this problem during the 1993-96 period. Six of them were using a nasogastric
tube, another one a gastrostomy (PEG). At the beginning of the enteral feeding
regimen their weight was -3.32 z-score (SD: -1.2) and for height: -2.11 z-score
(SD: -0.51). The underlying disease was gastroesophageal reflux (n = 4),
esophageal atresia (n = 1), short bowel syndrome (n = 1) and unexplained anorexia
(n = 1). RESULTS: The mean length of artificial nutrition was 20 months (SD:
11.5), although two of the patients still receive nocturnal enteral drip. Six
patients resumed a normal feeding pattern within 3 months to 2 years after
behavior modification program was started. CONCLUSION: According to our
experience, there is a critical period involved with oral feeding during the
first year of life. If not aware, children in transition for tube to oral feeding
may display oral-motor, sensory and developmental feeding problems.
PMID- 9644949
TI - [Characteristics of fats of some foods of the meats group and their relations
with health].
AB - The fatty acids and cholesterol contents of ten fresh protein foods were
determined, 6 meats (pork, rabbit, lamb, turkey, chicken and beef) and 4 fishes
(tuna, sea bream, hake and sardine); the fat quality by different chemical index
of the foods (saturated fat/polyunsaturated fat ratio, index of atherogenicity
and index of thrombogenicity) and the effect of their intakes on the health were
also determined. The study shows that the fat content was lower in meat pork than
lamb, rabbit, tuna, sea bream and sardine; and it was similar to chicken beef and
hake. Pork, chicken and turkey meat had the lowest content of myristic acid.
Fishes showed lower index of thrombogenicity than the other analyzed food and
pork, chicken and turkey showed the lowest atherogenicity index.
PMID- 9644950
TI - [Use of enteral nutrition products in a general hospital].
AB - The present work aims to study the use of enteral nutrition (EN) products during
the period between October 1996 and January 1997, in a general hospital with a
nutrition unit. The EN expenditure ascended to 3,343,475 Pesetas, with the
supplements representing the greatest cost percentage (39.1%). An indication
prescription study was carried out by reviewing 120 clinical histories of
patients who had received EN during that period. The patients originated in
different departments of the hospital, excluding the ICU, chronic patients,
pediatrics, and palliative care. Data regarding sex, age, diagnosis, diet used,
calories/day given, route of administration, and selection criterion for the diet
were analysed. The average age of the patients was 64.59 years. The most common
diagnoses were solid tumors (32.5% of the cases), followed by cerebrovascular
accidents (16.7% of the cases). The most commonly used EN preparation was the
Pentadrink hypercaloric diet (36.7% of the cases), followed by the standard diet
(25.8%). The route of administration used most frequently was the oral route in
63.3% of the cases. The calories/day given varied per diet, with this being 886
cal for the hypercaloric diet, and 1,839 cal for the standard diet. Among the
criteria for selecting an EN diet 50% of the patients had abnormal protein
metabolism and a normal digestive capacity with slight or moderate stress, 12.5%
were diabetic; and the remainder presented other criteria that influenced the
choice for a specific type of EN diet. From the analysis of the results it is
clear that Pentadrink is used as a supplement, and that there are patients with a
sometimes insufficient caloric supply.
PMID- 9644951
TI - [Some current questions concerning occupational diseases in Hungary].
AB - The author reviews the management of the professional diseases in Hungary from
the beginning till now. It can be stated that the number of the registered
professional diseases in Hungary has decreasing steadily. He thinks that this
tendency can be explained not only by the improvement of the labour higienic
conditions and systematic screening tests with biologic monitoring but also by
the increase of unemployment and the threatening of the latter of the workers as
well as the lack of the discipline of the registration. The change of the
economical structure resulted in the change of the problems concerning the
professional diseases too. The liquidation of the old large factories and the
development of many small economic plants represents a big problem of the labour
hygienic control of the latters and make difficult the prophylactic examinations
of all employees. This is a factor counteracting the further decrease of number
of professional diseases. The change of the spectrum of the professional diseases
is to be expected too. The criteria of the diagnosing, the therapy and the
prognosis of the professional diseases are described. The most effective method
of the medical prevention of the professional diseases in the precise fulfillment
of the prophylactic medical examinations.
PMID- 9644952
TI - [Examination of the sentinel lymph node in malignant melanoma].
AB - The authors report about a new "lymphatic-mapping" method (by means of patent
blue staining) by which it is able to detect regional (sentinel) lymph node, into
which the first metastasis is occurred. Experiences were made known with 15
patients. The by "lymphatic mapping" detected and removed sentinel lymph node has
an, important role not only in determination of staging, but also in indication
of prophylactic block-dissection, too.
PMID- 9644953
TI - ["Open abdomen" in the treatment of necrosis in acute pancreatitis].
AB - Eleven cases of acute necrotic pancreatitis had been treated by "open abdomen" at
the author's departments. Nine patients survived, but 2 patients had been lost in
MOF. Indication, technics and complications are discussed. The author's opinion
is, that--on the basis of a suitable indication--"open abdomen" is a good method
in the treatment of the necrosis in acute pancreatitis.
PMID- 9644954
TI - [Oral rehydration therapy in the management of diarrhea].
AB - Importance of oral rehydration solution in the treatment of diarrhoeal diseases
in well-known. It can be applied in all types of diarrhoea, practically, without
any side effects, complications, such hypernatraemia is avoidable. It has proved
to be effective for the dehydration, caused by diarrhoea, and for the diarrhoea,
too. The authors review the position of oralis rehydration liquid in the therapy
of diarrhoea, the pathophysiology and epidemiology of diarrhoeal diseases. The
therapeutic practices, suitable composition of oral rehydration solution, cost
benefit considerations, further possible indications of solution are discussed as
well. The authors give background information about the modification of the
composition of oral rehydration solution, recommended by the World Health
Organization, and call the attention to the importance of the alteration of
health officer's view about the oral rehydration therapy.
PMID- 9644955
TI - [Angina pectoris induced by pacemaker syndrome].
AB - Pacemaker syndrome is caused primarily by the lack of atrial kick and by
neurocardiogenic reflex mechanisms due to simultaneous atrial and ventricular
contractions. The most common clinical symptoms are dyspnoe, hypotension,
dizziness and syncopal attacks. A case report of a patient with pacemaker
syndrome is presented, in which the main clinical manifestation was a recurrent
chest pain. A VVI demand pacemaker was implanted because of sick sinus syndrome
ten years ago and shortly afterwards anginal attacks of rest developed. Coronary
angiography revealed a non-significant (25%) narrowing of the right coronary
artery (RCA). Casual and long-term ambulatory blood pressure (ABPM) measurements
elucidated that the patient occasionally has extremely low diastolic blood
pressure. This later phenomenon was confirmed and refined by a "beat-to-beat"
blood pressure measuring technique. The elimination of the pronounced "beat-to
beat" variability of arterial blood pressure and transient coronary hypoperfusion
due to implantation of an AV sequential bifocal pacemaker resulted in a full
disappearance of angina pectoris.
PMID- 9644956
TI - [Geza Farkas (1872-19340), professor of physiology].
PMID- 9644957
TI - [History of the stethoscope (Rene Theophile Hyacinthe Laennec)].
PMID- 9644958
TI - [National Registry of Automatic Implantable Defibrillators in 1996].
AB - The results of the Spanish Registry of Automatic Defibrillators implanted between
February 1996 and January 1997 are reported. A questionnaire per patient was
completed by every implanting physician, in every center. The questionnaire was
designed by the Section of Electrophysiology and Arrhythmias of the Spanish
Society of Cardiology. The data from 306 automatic defibrillators implanted were
reported. The percentage of defibrillators per inhabitant in Spain is close to 1
per 100,000. Eighty-five percent were first implants, while a 13% were
replacements. Most of the electrodes used were endocardial. Chronic ischemic
heart disease was found in 54% of the patients. Forty-six percent of the patients
had syncopal ventricular tachycardia, 31% ventricular fibrillation and 23%
sustained monomorphic ventricular tachycardia. The generator pocket was pectoral
in 87% of the patients and abdominal in 13%. The implant of the defibrillator was
associated with other cardiac surgery in only 3% of the patients.
PMID- 9644959
TI - ["The athlete's heart": most common electrocardiographic findings].
AB - The morphological and functional cardiac adaptations induced by physical training
may be reflected in several athlete's electrocardiographic variants. Rhythm and
heart rate disturbances are the most common findings, and sinus bradycardia is
the most frequent adaptation. Non-specific intraventricular conduction delay and
incomplete right bundle branch block are also frequent, but other bundle branch
and fascicular blocks are extremely rare. While the atrioventricular conduction
may be prolonged, the occurrence of first degree and type I second degree
atrioventricular blocks depends on the individual's susceptibility. Advanced
second and third degree atrioventricular blocks are exceptional, and when
present, the possibility of underlying heart disease must be excluded. High QRS
voltage is more frequent in male athletes, but its correlation with left
ventricular hypertrophy is low. The ST segment elevation in the so called "early
repolarization" pattern is typical of the athlete's electrocardiogram. Vagotonic
or high T wave voltages and U waves are also frequent when sinus bradycardia is
present. Tachyarrhythmias and increased automatism arrhythmias are rare and
usually benign. The increased vagal tone is responsible for the suppression of
the physiological and ectopic pacemakers. While Wolff-Parkinson-White syndrome
per se does not exclude an athlete from sports activity, the risk of a sudden
death makes it mandatory to perform an exhaustive cardiac evaluation. We may
conclude that no sport can be considered arrhythmogenic or as a predisposing
factor for malignant ventricular arrhythmias.
PMID- 9644960
TI - [Sympathetic reinnervation of the transplanted heart. Study using iodine-123
labeled meta-iodobenzylguanidine].
AB - INTRODUCTION AND OBJECTIVES: Metaiodobenzylguanidine (MIBG) is an analogue of
norepinephrine and its cardiac uptake shows sympathetic innervation. During the
heart transplantation the allograft becomes completely denervated. The present
study was conducted to assess the evolution of sympathetic re-innervation after
transplantation, and to related re-innervation with functional status. PATIENTS
AND METHODS: We studied 31 patients from 6 months to 12 years after
transplantation by 123I-MIBG studies to evaluate re-innervation and by
rest/exercise radionuclide ventriculography to evaluate cardiac function.
Myocardial MIBG uptake was quantified by calculating a heart-to-mediastinum ratio
(HMR). An HMR > 1.8 was considered normal, moderate between 1.8 and 1.6, mild
between 1.6 and 1.3, and absent < 1.3. RESULTS: HMR correlated with time after
transplantation (r = 0.607; p < 0.001). HMR of patients studied after 2 years of
transplantation was significantly higher (1.62 +/- 0.2 vs 1.34 +/- 0.2; p <
0.05). MIBG uptake was in the anterior region in 3 patients, in the antero
lateral region in 25, and in the antero-lateral and septal regions in 3. From a
functional point of view, peak filling rate at exercise was higher in patients
studied 2 years after the transplantation (2.7 +/- 0.8 edv/s vs 2.16 +/- 0.5
edv/s; p = 0.02). These patients also showed a higher increase of heart rate with
exercise (p < 0.005 vs p < 0.01). CONCLUSIONS: Sympathetic re-innervation
increase with time after heart transplantation, and is more frequently seen 2
years after transplantation. Sympathetic re-innervation first appears in the
anterior or the antero-lateral regions. A complete re-innervation of the
transplanted heart does not occur 12 years after transplantation.
PMID- 9644961
TI - [Electromagnetic interference between automatic defibrillators and digital and
analog cellular telephones].
AB - BACKGROUND AND OBJECTIVES: Functional pacemaker interference by mobile telephones
has been described with analogical systems and with possible greater influence,
digital systems, including inhibition and inadequate pacing. The influence of
both system has not been extensively studied in patients with implantable
cardioverter defibrillators (ICD). PATIENTS AND METHODS: We studied the influence
of mobile phones, both digital and analogic network, on the performance of
several models of defibrillators, in a standardised test set up designed to
provide high sensitivity. The purpose of our study was to establish whether there
are any influences on ICD functions, both in in vivo and in in vitro models.
Several mobile phones, with different transmission powers, were moved towards the
defibrillator and the electrode, under continuous documentation of defibrillator
sensing and interrogation afterwards. The experimental model was performed with
the aid of an arrhythmia simulator (Intersim) and demo-defibrillators. The tests
were repeated both in and out of a solution of saline water with an impedance
within normal human limits. RESULTS: Partial loss of telemetry was found in 14
patients, 8 with analogical phones and 6 with digital phones. Fourteen patients
showed alterations only on the surface electrocardiogram channel and five on the
intracavitary channel. The same results were reproduced in the in vitro model.
However, the in vitro test allowed us to simulate multiple ventricular
arrhythmias, and demonstrate the normal sensing and functioning of the
defibrillator during a "spontaneous" arrhythmia. After testing, we demonstrate
that no real oversensing/undersensing was documented in any device. There was no
evidence of ICD reprogramming or pacing inhibition. In particular, no inadequate
therapies were delivered. CONCLUSIONS: a) in our series, we have not demonstrated
clinically significant electromagnetic interferences with mobile phones of
digital or analogical networks: b) the in vitro model allowed us to conclude that
even if a spontaneous arrhythmia appears, the function of the defibrillator is
not altered; c) the use of mobile phones seems to be safe for defibrillator
patients, and d) however, some basic rules, such as to maintain the phone at
least 15 cm away from the defibrillator, are advised.
PMID- 9644962
TI - [Long-term follow up of patients with nodal reentry tachycardia who had undergone
radiofrequency ablation].
AB - INTRODUCTION: The aim of this study was to assess the long term results (minimum
of 3 years) of radiofrequency catheter ablation in patients with common (slow
fast) atrioventricular nodal reentrant tachycardia. PATIENTS AND METHODS: Sixty
consecutive patients (mean age 56 +/- 16 years, range 14 to 83, 16 men and 44
women) underwent slow pathway (n = 51, Group A) or fast pathway (n = 9, Group B)
radiofrequency catheter ablation between January 1992 and March 1994. All
patients were followed at 1, 3, 6 and 12 months after ablation with serial
examinations and electrocardiograms and the last follow-up was made on April
1997. RESULTS: During a mean follow-up period of 48 +/- 7 months (range 38 to 63)
all evaluated patients remained asymptomatic. Eight recurrences were observed at
a mean of 1 +/- 2 months (range, 0.5 to 7) after a successful ablation procedure.
A second procedure was effective in eliminating the dual atrioventricular nodal
pathway in each of them. In Group A patients, the pre-ablation PR interval, at 12
months after ablation and at last follow-up were 122 +/- 11, 124 +/- 13 and 124
+/- 15 ms, respectively. In Group B patients, the pre-ablation PR interval, at 12
months after ablation and at last follow-up were 130 +/- 24, 200 +/- 12, 200 +/-
24 ms, respectively. No significant atrioventricular conduction disturbances in
any patient were observed. One patient developed a new onset left bundle branch
block and 4 patients died of noncardiac causes. CONCLUSIONS: In patients with
atrioventricular nodal reentrant tachycardia, radiofrequency catheter ablation is
a safe and effective therapy, with substantial good results that persist during
long term follow-up, with a low recurrence rate and without complications during
short and long term outcome.
PMID- 9644963
TI - [Quantification of myocardial ischemia in regions dependent on occluded coronary
arteries in patients without previous infarction].
AB - INTRODUCTION AND OBJECTIVES: The aim of this study is to assess myocardial
ischemia in regions with no infarction dependent occluded coronary arteries.
PATIENTS AND METHODS: 149 patients with proved coronary artery disease and
without previous myocardial infarction were studied by 99mTc-MIBI SPECT (long
protocol) and coronary angiography. The extent of the uptake reversibility was
quantified in 3 regions (antero-septal, inferior and lateral) of the polar maps,
assessing the percentage of each region that had a > 10% difference resulting
from the rest uptake minus the stress uptake. The regions dependent on one
occluded artery were compared to those dependent on non-occluded arteries. In the
regions dependent on one occluded artery a comparison was also made between those
which had a good collateral circulation and those which did not. RESULTS: Fifty
four out of 149 patients (36%) had at least one occluded coronary artery (20
anterior descending, 22 right and 27 circumflex coronary arteries). In the visual
analysis, reversible defects were observed in all patients with occlusion of the
anterior descending and the right coronary artery, but only in half of the
occlusions of the circumflex coronary artery. The extent of this reversibility
was significantly higher in the regions dependent on occluded arteries and was
highly variable, though lower when good collateral circulation was present.
CONCLUSIONS: Reversible defects were always observed in the occlusions of the
left anterior descending and right coronary arteries, but only in half of those
of the circumflex artery. The extent of the ischemia was higher in the regions
dependent on one occluded coronary artery, mainly when there was an absence of
good collateral circulation.
PMID- 9644964
TI - [Pathology of the heart of noncardiac origin. VIII. Cocaine and the heart].
AB - The marked increase in cocaine consumption observed in recent decades, has led to
the identification of previously unknown multiple medical problems.
Cardiovascular complications related to cocaine abuse include myocardial ischemia
and infarction, myocarditis, cardiomyopathy, rhythm disturbances and sudden
death, endocarditis, pneumopericardium and left ventricular hypertrophy. Although
the mechanisms involved in cocaine-related cardiac diseases are multiple, many
cardiac complications in these patients are caused in part or totally by an
increase in adrenergic activity due to the blockade of catecholamine reuptake
induced by the drug.
PMID- 9644965
TI - [Left atrial dissection and infective endocarditis].
AB - A rare case of left atrial dissection as a consequence of infectious endocarditis
is reported. We present a patient with infectious endocarditis with involvement
of mitral and aortic valves; in whom the trans-esophageal echocardiography was
able to visualise the left atrial dissection. This complication has been reported
after surgical repair of the mitral valve, but never in infectious endocarditis.
PMID- 9644966
TI - [Electrocardiographic changes in hypoglycemia].
AB - Several electrocardiographic anomalies have been described in association with
hypoglycaemia. We report the case of a 70-year-old woman with hypoglycaemic coma
whose electrocardiogram showed significant conduction anomalies, including
atrioventricular block and intraventricular conduction disturbances, and
repolarization abnormalities. These electrocardiographic changes disappeared
after intravenous glucose administration.
PMID- 9644967
TI - [Ellis-van Creveld syndrome: an easy early diagnosis?].
AB - Ellis-Van Creveld syndrome is a rare chondroectodermal dysplasia. Congenital
heart disease is present in more than one-half of cases. The majority are partial
atrioventricular septal defects and affect the atrial septum. Although isolated
cases of the syndrome are uncommon, an early diagnosis is made in most of the
patients because of their cardinal manifestations. The cases of two gypsy
brothers with Ellis-Van Creveld syndrome and congenital heart disease (ostium
primum atrial septal defect and single atrium), diagnosed during adulthood, are
presented.
PMID- 9644968
TI - [Coronary spasm and heart arrest caused by ventricular fibrillation].
AB - We report the cases of three young men, heavy smokers, without previous heart
disease and who were resuscitated after cardiac arrest due to ventricular
fibrillation attributed to coronary spasm. All of them complained of atypical
chest pain and the exercise testing, echocardiogram and coronary angiography were
normal. The first case was diagnosed by Holter monitoring and by provocative
testing with intracoronary ergonovine; the second by provocative testing with
intracoronary acetylcholine and the third by Holter monitoring. The patients were
treated with a calcium antagonist and/or nitrates and in the follow up they
remained asymptomatic.
PMID- 9644969
TI - Prions are copper-binding proteins.
PMID- 9644970
TI - A rule for termination-codon position within intron-containing genes: when
nonsense affects RNA abundance.
PMID- 9644971
TI - Diacylglycerols and phosphatidates: which molecular species are intracellular
messengers?
AB - In eukaryotes, many receptor agonists use phospholipase-generated lipids as
intracellular messengers. Receptor occupation stimulates the production of
polyunsaturated 1,2-diacylglycerols by phosphatidylinositol-4,5-bisphosphate
specific phospholipases C and/or of mono-unsaturated and saturated phosphatidates
by phospholipase-D-catalysed phosphatidylcholine breakdown. The primary
phospholipase products are rapidly metabolized: polyunsaturated 1,2
diacylglycerols are converted to polyunsaturated phosphatidates by diacylglycerol
kinase; mono-unsaturated and saturated phosphatidates are dephosphorylated to
give mono-unsaturated and saturated 1,2-diacylglycerols by phosphatidate
phosphohydrolase. The phospholipase-generated polyunsaturated 1,2-diacylglycerols
and mono-unsaturated and saturated phosphatidates appear to be intracellular
messengers, whereas their immediate metabolites probably do not have signalling
functions.
PMID- 9644972
TI - The PCI domain: a common theme in three multiprotein complexes.
PMID- 9644973
TI - A novel oxidoreductase family sharing a conserved FAD-binding domain.
PMID- 9644974
TI - Ribosomal protein structures: insights into the architecture, machinery and
evolution of the ribosome.
AB - Models of the bacterial ribosome based on recent structural analyses are
beginning to provide new insights into the protein synthetic machinery. Central
to evolving models are the high-resolution structures of individual ribosomal
proteins, which represent detailed probes of their local RNA and protein
environments. Ribosomal proteins are extremely ancient molecules; the structures
therefore also provide a unique window into early protein evolution. Many of the
proteins contain domains that are present in more recently evolved families of
RNA- and DNA-binding proteins. Such structural homology can be used to predict
mechanisms by which proteins interact with RNA in the ribosome.
PMID- 9644975
TI - Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling
pathway.
AB - The Ets family of transcription factors includes nuclear phosphoproteins that are
involved in cell proliferation, differentiation and oncogenic transformation. The
family is defined by a conserved DNA-binding domain (the ETS-DBD), which forms a
highly conserved, winged, helix-turn-helix structural motif. As targets of the
Ras-MAPK signaling pathway, Ets proteins function as critical nuclear integrators
of ubiquitous signaling cascades. To direct signals to specific target genes, Ets
proteins interact with (other) transcription factors that promote the binding of
Ets proteins to composite Ras-responsive elements.
PMID- 9644976
TI - Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase.
AB - In mammals and yeast, 5-aminolaevulinic acid dehydratase is a zinc-dependent
enzyme that catalyses the synthesis of porphobilinogen-the pyrrole building block
that is incorporated into all modified tetrapyrroles, including haem, chlorophyll
and vitamin B12. The X-ray structure of this enzyme reveals how substitution of
the catalytically important zinc ion by lead inactivates the enzyme and causes a
form of pseudo-porphyria.
PMID- 9644977
TI - The J-domain family and the recruitment of chaperone power.
AB - The defining feature of the Hsp40 chaperone family is a approximately 70-amino
acid-residue signature, termed the J domain, that is necessary for orchestrating
interactions with its Hsp70 chaperone partner(s). J-domain proteins play
important regulatory roles as co-chaperones, recruiting Hsp70 partners and
accelerating the ATP-hydrolysis step of the chaperone cycle. Certain proteins
could have acquired a J domain in order to present a specific substrate(s) to an
Hsp70 partner and thus capitalize upon chaperone activities when carrying out
cellular functions. J-domain proteins participate in complex biological
processes, such as cell-cycle control by DNA tumor viruses, regulation of protein
kinases and exocytosis.
PMID- 9644978
TI - [Experience in the use of doxazosin in patients with benign hyperplasia of the
prostate].
AB - Selective alpha-1-adrenoblockers are thought promising in current conservative
treatment of benign prostatic hyperplasia (BPH). The trial of doxazosin (cardura)
-a selective alpha-blocker--included 78 BPH patients with obstructive urination.
All the patients received a single daily dose of doxazosin 4-8 mg (mean 5.7 mg).
60 patients on placebo served as control. The comparison of the effects observed
in the study vs control group has demonstrated that doxazosin has a favourable
effect on BPH: it improved quality of life, relieved obstructive symptoms,
reduced amount of residual urine. There is objective urodynamic evidence on
decreased infravesical obstruction.
PMID- 9644979
TI - [Combined use of 5 alpha-reductase inhibitors and alpha-l adrenergic receptor
blockers in patients with benign prostatic hyperplasia].
AB - 88 patients with benign prostatic hyperplasia (BPH) were given the inhibitor of 5
alpha-reductase proscar (finasteride, Merck and Co. Inc., USA) for 12-14 months
and uroselective blocker of alpha-adrenoreceptors alfuzosin (dalfas, Synthelabo
Group, France) for 4-5 months. The patients were examined before the combined
treatment and on the treatment month 1, 3, 6 and 12. The proscar plus alfuzosin
combination produced a response after 2-3-week treatment due to alpha-blocker
Further, the effect was enhanced by the action of inhibitor of 5 alpha-reductase.
Combination of alfuzosin with proscar meets three principal requirements demanded
of BPH chemotherapy: improves urination, inhibits the growth of adenomatous
tissue, diminishes the size of the enlarged prostate.
PMID- 9644980
TI - [Diagnosis of the "valve effect" of the middle lobe of prostate in benign
prostatic hyperplasia and choice of the treatment method].
AB - As there are still no accurate criteria of assessing middle-lobe prostatic benign
hyperplasia contribution through the "valve effect" to development of
infravesical obstruction, the authors propose to introduce "miction" transrectal
ultrasonic study. This study provides evidence allowing to divide patients with
middle-lobe prostatic benign hyperplasia into three groups by the degree of the
"valve effect". This enables differential approach to choice of the scope of the
operative intervention.
PMID- 9644981
TI - [Changes in central hemodynamics in transurethral prostate resection under
epidural anesthesia].
AB - Central hemodynamics was studied in 53 patients divided into 3 groups who had
transurethral resection of the prostate under epidural anesthesia. Patients with
uneventful course of surgery (group 1) had favourable rearrangement of
hemodynamic parameters in response to epidural anesthesia. In patients of group 2
hemodynamics was characterized by addition of negative effects of relative
hypovolemia. A significant fall of central venous pressure was found in group 3.
This low venous pressure resulted from the epidural block and contributed much to
development of hyponatremia in these patients.
PMID- 9644982
TI - [Long-term results of plastic surgery in hydronephrosis in children].
AB - 94 children (109 kidneys) with congenital hydronephrosis were treated in 1989
1997. 67 of them underwent 76 plastic operations: Andersen-Hynes operation on the
ureteropelvic segment without pelvic resection (n = 53), antevasal pyelopyelo-
and ureteropyeloanastomosis (n = 18), ureteropyelolysis (n = 5). Excellent, good
and satisfactory results were obtained in 16.5, 50.6 and 30.4% of cases,
respectively. The analysis of changes in the renal-cortical index before and
after plastic operation with reference to hydronephrosis stage and form, type of
the pelvis evidenced that the best treatment outcomes were achieved in children
with open hydronephrosis stage II having extrarenal pelvis. Poor outcomes
occurred in closed hydronephrosis stage III and intrarenal pelvis. Renal
planimetry, as one of highly informative diagnostic techniques, can be used in
assessing results obtained in hydronephrosis treatment.
PMID- 9644983
TI - [Diagnosis and surgical treatment of tumors of the upper urinary tract].
AB - The author believes that in diagnosis of tumors of the upper urinary tracts more
information can be obtained at ureteropyeloscopy with retrograde contrasting of
the urinary tracts and, if necessary, biopsy of abnormal urothelium regions. 19
patients with pelvic and 4 patients with ureteral tumor were operated on. 2(8.7%)
patients with tumor in the lower third of the ureter underwent resection with
Boari operation, classic nephroureterectomy with bladder resection was made in
15(65.2%) patients, transurethral resection of the wall of the bladder, ostium
and distal ureter followed by nephroureterectomy was performed in 6(26.1%)
patients. The latter operative procedure is radical but less traumatic. Five-year
survival made up 73.9%.
PMID- 9644984
TI - [Variants of dysfunction of the upper urinary tract in urolithiasis].
AB - Registration of contractility of the upper urinary tracts (UUT) at multichannel
impedance ureterography was conducted in 30 patients with concrements in the
kidneys and ureters before extracorporeal lithotripsy. By defects in urodynamics,
the patients were divided into 4 groups. The most severe affection of urodynamics
(low amplitude of the peristalsis, high tonicity of UUT wall) occurred in group
4. From group 1 to 4 contraction arrhythmia, deformity of contraction complexes,
retrograde contraction waves were increasing. The index has been calculated for
estimation of UUT performance in transporting urine.
PMID- 9644985
TI - [Effects of indirect electrochemical blood oxidation by sodium hypochlorite
solution on the course on inflammatory process in the kidneys and urinary tract].
AB - The action of indirect electrochemical blood oxidation with 0.06% solution of
sodium hypochlorite on kidney and urinary inflammation was studied in experiments
on 60 non-inbred rat females of 200-250 g body weight. The animals were
intravesically infected through the catheter with E. coli and Ps. aeruginosa. 3
days later, after histological verification of acute pyelonephritis, ureteritis,
cystitis, the animals were injected intraperitoneally 1.0 and 2.0 ml daily of
sodium hypochlorite solution (control animals) or 0.89% solution of sodium
chloride. Though no reliable decrease of the bacterial contamination was
achieved, histologically, there was a marked reduction in morphological signs of
the inflammation in the kidneys, ureter and urinary bladder on the first day
after beginning of electrochemical blood oxidation with solution of sodium
hypochlorite in experimental groups. In experimental group rats morphological
signs of urinary and renal inflammation for both infections disappeared on days 7
and 10, respectively. In the control animals morphological signs of the
inflammation remained after 10 days. Moreover, purulent inflammation was
registered in the controls infected with Ps. aeruginosa.
PMID- 9644986
TI - [Effects of antihypertensive therapy on renal function in nephrogenic
hypertension].
AB - Radionuclide tracing was performed to study renal function before and after
hypotensive therapy in 95 patients suffering from nephrogenic hypertension with
renal failure. It is shown that if hypotensive therapy in such patients brings
about a blood pressure fall more than 25% of the initial blood pressure, renal
function declines, the suppression being especially evident in severe renal
insufficiency.
PMID- 9644987
TI - [Vascular complications of kidney transplantation].
AB - 584 kidney transplantations (208 from cadaveric donors, 376 from living relative
donors) were performed in Medical Faculties of the Istambul University in 1986
1997. Thrombosis of the renal artery was observed in 2 patients (0.35%). One of
them had diffused arterial atherosclerosis 4 months after the kidney
transplantation. In spite of two successful thrombectomies, the patient died 3
months after the last surgical procedure from cerebral thrombosis. The other
patient underwent nephrectomy. Hypertension was observed in 63 patients. In 5 of
them about 50% stenosis of the anastomotic area was detected by doppler duplex
scan and selective angiogram. Transluminal angioplasty was performed in one
patient, open surgical correction in one case. Renal vein thrombosis took place
in 1 (0.2%) patient. In 2 cases (0.35%) 5 and 12 years after the transplantation
aortic aneurysmal dissection was observed.
PMID- 9644988
TI - [Comprehensive assessment of the gastroduodenal mucosa before and after
methylprednisolone pulse-therapy in children with chronic glomerulonephritis].
PMID- 9644989
TI - [Beta 2-microglobulin as a criterion of dysfunction in the regulation of proximal
tubular activity in mercuric chloride-induced nephropathy].
AB - Sublimate nephropathy--modelled pathology of proximal nephron--serves as
illustration of a pathogenetic role in development of proximal tubular
dysfunction of enhanced vasoconstrictive potential of angiotensin II in plasma,
angiotensin II and thromboxane B2 in renal cortex. The multiple regression
equation has been calculated. The proportional contribution of plasma angiotensin
II, atrial natriuretic peptide of plasma, cortical angiotensin II, cortical
thromboxane B2 to regulation of proximal nephron function was the following:
26.85, 32.72, 10.51 and 10.56%, respectively.
PMID- 9644990
TI - [Diagnosis and treatment of erectile dysfunction].
AB - Pathogenesis of erectile dysfunction is well studied now. So another problem
arises: how to choose individual methods of diagnosis and treatment as well as
sequence of diagnostic and therapeutic measures. Our method of purposeful
approach to diagnosis and treatment of erectile dysfunction is based on the
choice of the patient who decides himself the scope and invasiveness of the
diagnosis and treatment. The patient makes his choice after he is informed about
all available diagnostic techniques and treatment methods.
PMID- 9644991
TI - [Use of lysozyme in the treatment of male infertility].
AB - The results of the study of the influence of lysozyme on fertile characteristics
of ejaculate obtained from sterile patients are presented. Improvement of
functional activity of spermatozoa in vitro due to lysozyme has been determined.
The method of the treatment of infertile couples by homologous insemination is
proposed.
PMID- 9644992
TI - [Foreign body in the bladder].
PMID- 9644993
TI - [Bacteriotoxic shock as complication of urolithiasis].
PMID- 9644994
TI - [Overview of lipoprotein and lipids].
PMID- 9644995
TI - [Apo A-I deficiency].
PMID- 9644996
TI - [Apo A-I variant].
PMID- 9644997
TI - [Tangier disease].
PMID- 9644998
TI - [Apolipoprotein A-II abnormality].
PMID- 9644999
TI - [Abnormal apolipoprotein B].
PMID- 9645000
TI - [Familial hypo beta-lipoproteinemia].
PMID- 9645001
TI - [Apolipoprotein B-100 variants].
PMID- 9645002
TI - [Normotriglyceridemic abetalipoproteinemia].
PMID- 9645003
TI - [Hypo beta-lipoproteinemia with selective deletion of apo B-48].
PMID- 9645004
TI - [Familial defective apolipoprotein B-100].
PMID- 9645005
TI - [Abnormalities of apolipoprotein E (type III hyperlipoproteinemia)].
PMID- 9645006
TI - [Apolipoprotein C-II deficiency].
PMID- 9645007
TI - [Congenital hypoalphalipoproteinemia].
PMID- 9645008
TI - [Hyperalphalipoproteinemia].
PMID- 9645009
TI - [Primary type V hyperlipidemia].
PMID- 9645011
TI - [Primary hypertriglyceridemia].
PMID- 9645010
TI - [Familial hypercholesterolemia].
PMID- 9645012
TI - [Familial combined hyperlipidemia].
PMID- 9645013
TI - [Abetalipoproteinemia].
PMID- 9645014
TI - [Familial lipoprotein lipase deficiency].
PMID- 9645015
TI - [Lipoprotein lipase inhibitory factor].
PMID- 9645016
TI - [Hepatic triglyceride lipase deficiency, hepatic lipase deficiency].
PMID- 9645017
TI - [High Lp (a) concentrations].
PMID- 9645018
TI - [Lecithin-cholesterol acyltransferase deficiency and fish eye disease].
PMID- 9645019
TI - [Polygenic hypercholesterolemia].
PMID- 9645020
TI - [Sitosterolemia].
PMID- 9645021
TI - [Cerebrotendinous xanthomatosis (CTX)].
PMID- 9645022
TI - [Membranous lipodystrophy].
PMID- 9645023
TI - [Introduction to porphyrin and heme].
PMID- 9645024
TI - [Acute intermittent porphyria (AIP)].
PMID- 9645025
TI - [ALAD deficiency porphyria (ADP)].
PMID- 9645026
TI - [Variegate porphyria (VP)].
PMID- 9645027
TI - [Hereditary coproporphyria (HCP)].
PMID- 9645028
TI - [Porphyria cutanea tarda].
PMID- 9645029
TI - [Hepatoerythropoietic porphyria].
PMID- 9645030
TI - [Congenital erythropoietic porphyria].
PMID- 9645031
TI - [Erythropoietic protoporphyria].
PMID- 9645032
TI - [Sideroblastic anemia].
PMID- 9645033
TI - [Inborn errors of trace metals].
PMID- 9645034
TI - [Wilson disease].
PMID- 9645035
TI - [Menkes disease].
PMID- 9645036
TI - [Ceruloplasmin deficiency or aceruloplasminemia].
PMID- 9645037
TI - [Hemochromatosis].
PMID- 9645038
TI - [Atransferrinemia].
PMID- 9645039
TI - [Molybdenum cofactor deficiency].
PMID- 9645040
TI - [Isolated sulfite oxidase deficiency].
PMID- 9645041
TI - [Introduction to vitamin].
PMID- 9645042
TI - [Congenital folate malabsorption].
PMID- 9645043
TI - [Glutamate-formiminotransferase deficiency].
PMID- 9645044
TI - [Methylenetetrahydrofolate reductase deficiency].
PMID- 9645045
TI - [Transcobalamin II deficiency].
PMID- 9645046
TI - [Inherited disorders of cobalamin metabolism].
PMID- 9645047
TI - [Holocarboxylase synthetase deficiency (early-onset multiple carboxylase
deficiency)].
PMID- 9645048
TI - [Biotinidase deficiency (late-onset multiple carboxylase deficiency)].
PMID- 9645049
TI - [Vitamin B1 dependency].
PMID- 9645050
TI - [Vitamin B6 dependency syndrome (vitamin B6 dependent seizures, convulsions)].
PMID- 9645051
TI - [Vitamin D dependency (type I, type II)].
PMID- 9645052
TI - [Vitamin E deficiency (alpha-tocopherol transfer protein deficiency)].
PMID- 9645053
TI - [Bilirubin and bile acid: introduction].
PMID- 9645054
TI - [Neonatal jaundice, hereditary hemolytic anemia].
PMID- 9645055
TI - [Crigler-Najjar syndrome].
PMID- 9645056
TI - [Gilbert's syndrome].
PMID- 9645057
TI - [Dubin-Johnson syndrome].
PMID- 9645058
TI - [Rotor syndrome].
PMID- 9645059
TI - [Benign recurrent intrahepatic cholestasis (Summerskill disease)].
PMID- 9645060
TI - [Fasting hyperbilirubinemia].
PMID- 9645061
TI - [3 beta-hydroxy-delta 5-C27-steroid-oxidoreductase/isomerase deficiency].
PMID- 9645062
TI - [Delta 4-3-oxosteroid 5 beta-reductase deficiency].
PMID- 9645063
TI - [27-Hydroxylase deficiency (cerebrotendinous xanthomatosis)].
PMID- 9645064
TI - [Peroxisomal disorders].
PMID- 9645065
TI - [Introduction to peroxisomal disorders].
PMID- 9645066
TI - [Zellweger syndrome].
PMID- 9645067
TI - [Neonatal adrenoleukodystrophy].
PMID- 9645068
TI - [Infantile Refsum disease].
PMID- 9645069
TI - [Rhizomelic chondrodysplasia punctata (RCDP)].
PMID- 9645070
TI - [Dihydroxyacetonephosphate acyltransferase (DHAP-AT) deficiency and alkyl-DHAP
synthase deficiency].
PMID- 9645071
TI - [X-linked adrenoleukodystrophy (ALD)].
PMID- 9645072
TI - [Peroxisomal acyl-CoA oxidase deficiency].
PMID- 9645073
TI - [Bifunctional enzyme deficiency].
PMID- 9645074
TI - [Peroxisomal 3-ketoacyl-CoA thiolase deficiency].
PMID- 9645075
TI - [Acatalasemia, Takahara disease].
PMID- 9645076
TI - [Refsum disease].
PMID- 9645077
TI - [Primary hyperoxaluria type 1 (PH1)].
PMID- 9645078
TI - [Other peroxisomal diseases].
PMID- 9645079
TI - [Lysosomal diseases: an overview].
PMID- 9645080
TI - [Glycogen storage disease type II].
PMID- 9645081
TI - [Lysosomal glycogen storage disease without acid maltase deficiency (Danon's
disease)].
PMID- 9645082
TI - [Gaucher disease].
PMID- 9645083
TI - [Niemann-Pick disease [type A and B] (acid sphingomyelinase deficiencies)].
PMID- 9645084
TI - [Fabry disease (alpha-galactosidase deficiency)].
PMID- 9645085
TI - [Schindler disease/Kanzaki disease [alpha-N-acetylgalactosaminidase deficiency]].
PMID- 9645086
TI - [Krabbe disease (globoid cell leukodystrophy)].
PMID- 9645087
TI - [Metachromatic leukodystrophy].
PMID- 9645088
TI - [Multiple sulfatase deficiency].
PMID- 9645089
TI - [Farber disease [Farber lipogranulomatosis], acid ceramidase deficiency].
PMID- 9645090
TI - [Tay-Sachs disease (beta-hexosaminidase alpha-chain deficiency)].
PMID- 9645091
TI - [Sandhoff disease (beta-hexosaminidase alpha-chain deficiency)].
PMID- 9645092
TI - [GM2 ganglioside activator protein deficiency].
PMID- 9645093
TI - [beta-Galactosidosis (acid beta-galactosidase deficiency: GM1 gangliosidosis,
Morquio B disease)].
PMID- 9645094
TI - [Galactosialidosis].
PMID- 9645095
TI - [GM2 activator protein deficiency (AB variant form of GM2 gangliosidosis)].
PMID- 9645096
TI - [Prosaposin deficiency].
PMID- 9645097
TI - [Saposin B deficiency].
PMID- 9645098
TI - [Saposin C deficiency].
PMID- 9645099
TI - [Batten disease].
PMID- 9645100
TI - [Acid lipase deficiency (Wolman disease and cholesteryl ester storage disease:
CESD)].
PMID- 9645101
TI - [Mucopolysaccharidosis type I (Hurler syndrome, Scheie syndrome)].
PMID- 9645102
TI - [Mucopolysaccharidosis type II (Hunter syndrome)].
PMID- 9645103
TI - [Mucopolysaccharidosis type III (Sanfilippo syndrome)].
PMID- 9645104
TI - [Mucopolysaccharidosis type IV (Morquio syndrome, beta-galactosidase
deficiency)].
PMID- 9645105
TI - [Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome)].
PMID- 9645106
TI - [Mucopolysaccharidosis type VII (Sly disease)].
PMID- 9645107
TI - [Congenital hyaluronidase deficiency].
PMID- 9645108
TI - [Alpha-mannosidosis].
PMID- 9645109
TI - [Beta-mannosidosis].
PMID- 9645110
TI - [Fucosidosis].
PMID- 9645111
TI - [Sialidosis].
PMID- 9645112
TI - [Aspartylglucosaminuria].
PMID- 9645113
TI - [Disorders of phosphorylation system of lysosomal enzymes [mucolipidosis II,
III]].
PMID- 9645114
TI - [Carbohydrate-deficient glycoprotein (CDG) syndrome (Jaeken syndrome)].
PMID- 9645115
TI - [Mitochondria: an overview].
PMID- 9645116
TI - [Electron transfer complex I deficiency].
PMID- 9645117
TI - [Electron transfer complex II deficiency].
PMID- 9645118
TI - [Electron transfer complex III deficiency].
PMID- 9645119
TI - [Electron transfer complex IV (cytochrome c oxidase) deficiency].
PMID- 9645120
TI - [Mitochondrial DNA depletion].
PMID- 9645121
TI - [Introduction to connective tissue].
PMID- 9645122
TI - [Osteogenesis imperfecta].
PMID- 9645123
TI - [Ehlers-Danlos syndrome].
PMID- 9645124
TI - [Chondrodysplasia].
PMID- 9645125
TI - [Alport syndrome].
PMID- 9645126
TI - [Epidermolysis bullosa hereditaria].
PMID- 9645127
TI - [Marfan syndrome].
PMID- 9645128
TI - [Marfan-related conditions].
PMID- 9645129
TI - [Pseudoxanthoma elasticum].
PMID- 9645130
TI - [Membrane transport system].
PMID- 9645131
TI - [Selective congenital glucose, galactose malabsorption in the small intestine].
PMID- 9645132
TI - [Familial renal glycosuria].
PMID- 9645133
TI - [Cystinuria].
PMID- 9645134
TI - [Lysinuric protein intolerance and other cationic aminoacidurias].
PMID- 9645135
TI - [Hartnup disease].
PMID- 9645136
TI - [Familial iminoglycinuria].
PMID- 9645137
TI - [Histidinuria due to a renal tubular defect].
PMID- 9645138
TI - [Blue diaper syndrome].
PMID- 9645140
TI - [Renal tubular acidosis].
PMID- 9645139
TI - [Methionine malabsorption syndrome].
PMID- 9645141
TI - [Fanconi syndrome].
PMID- 9645142
TI - [Oculocerebrorenal syndrome of Lowe].
PMID- 9645143
TI - [Hypophosphatemic vitamin D resistant rickets].
PMID- 9645144
TI - [Hereditary renal hypouricemia].
PMID- 9645145
TI - [Lysosomal transport disorders: cystinosis and sialic acid storage disorders].
PMID- 9645146
TI - [Cystic fibrosis].
PMID- 9645147
TI - [Alstrom syndrome].
PMID- 9645148
TI - [Ataxia-telangiectasia].
PMID- 9645149
TI - [Carbonic anhydrase II deficiency].
PMID- 9645150
TI - [Lipodystrophy].
PMID- 9645151
TI - [Norrie disease].
PMID- 9645152
TI - [Alpha 1-antitrypsin deficiency].
PMID- 9645153
TI - [Hereditary amyloidosis].
PMID- 9645154
TI - [Inborn errors of catecholamine metabolism].
PMID- 9645155
TI - [Primary hypomagnesemia].
PMID- 9645156
TI - [Cholinesterase deficiency].
PMID- 9645157
TI - [Dipeptidase deficiency].
PMID- 9645158
TI - [Alloalbuminemia and analbuminemia].
PMID- 9645159
TI - [Congenital enterokinase deficiency].
PMID- 9645160
TI - [Congenital chloride diarrhea].
PMID- 9645161
TI - [Congenital trypsinogen deficiency].
PMID- 9645162
TI - [Congenital lipase deficiency].
PMID- 9645163
TI - [Hypophosphatasia].
PMID- 9645164
TI - [Trimethylaminuria].
PMID- 9645165
TI - [Anhaptoglobinemia and hypohaptoglobinemia].
PMID- 9645166
TI - [Albinism].
PMID- 9645168
TI - Prenatal ultrasonography in rural hospitals.
PMID- 9645167
TI - Computed tomography, magnetic resonance imaging and positron emission tomography
in non-Hodgkin's lymphoma.
AB - Certain aspects of the use of CT, MR imaging and PET were evaluated in patients
with non-Hodgkin's lymphoma (NHL) with the aim of determining whether these
methods may provide practical guidance for improving the management of these
patients. Subjective evaluation of the tumor pattern on CT images, and
quantification of tracer uptake using 11C methionine (11C Met) and [18F]
fluorodeoxyglucose (18FDG) PET in patients with NHL, were performed to determine
their relations to malignancy grade. An inhomogeneous tumor pattern (I) was found
on CT in 75% of high-grade tumors, whereas 68% of low-grade tumors were
homogeneous (H). Sixteen (94%) of the 17 tumors with a severely inhomogeneous
pattern (I) were high-grade NHL, while 22 (72%) of the 29 homogeneous tumors (H)
were low-grade. All tumors were clearly visualized with both 11C Met and 18FDG
PET. The uptake values for 18FDG were significantly-higher in high- than in low
grade tumors, while no significant differences between the prognostic groups were
found for 11C Met. A subjective evaluation of the tumor pattern on CT and on MR
images was performed. An inhomogeneity index (IH8) was also used in MR images to
make a quantitative assessment of the degree of inhomogeneity to determine their
relation to prognosis. Patients with localized NHL, treated with radiotherapy,
had an excellent prognosis irrespective of the degree of inhomogeneity, while
patients with generalized disease, treated with chemotherapy, had a poor
prognosis if the tumors were heterogeneous. Among chemotherapy-treated patients,
all 9 patients with high IH8 values (> 2.56) on MR images and 9 out of 11
patients with severe inhomogeneities on CT images died. All patients with gastric
NHL except for one patient with low-grade NHL of the MALT type displayed high
18FDG uptake at PET corresponding to the pathological findings at endoscopy
and/or CT. 18FDG correctly excluded gastric NHL in a patient with benign gastric
ulcer, but was unable to discriminate between gastric NHL and gastric carcinoma.
The results suggest that 18FDG PET may demonstrate the extension of NHL in the
gastric wall more accurately than CT and endoscopy. The prognostic importance of
the size of a residual mass after completion of chemotherapy, and of tumor
regression rates during chemotherapy, was evaluated in patients with high-grade
NHL. Neither a large tumor size before treatment nor a large residual tumor after
treatment correlated with relapse. It appears, however, as if the response rate
halfway through the therapy may predict the recurrence rate, although statistical
significance was not reached.
PMID- 9645169
TI - Prenatal ultrasonography in rural hospitals.
PMID- 9645170
TI - Answering the hard questions about thrombolysis.
PMID- 9645171
TI - Answering the hard questions about thrombosis.
PMID- 9645172
TI - Answering the hard questions about thrombolysis.
PMID- 9645173
TI - Unexpected death related to restraint for excited delirium: a retrospective study
of deaths in police custody and in the community.
AB - BACKGROUND: Some people in states of excited delirium die while in police
custody. Emerging evidence suggests that physical restraint in certain positions
may contribute to such deaths. In this study the authors determined the frequency
of physical restraint among people in a state of excited delirium who died
unexpectedly. METHODS: The authors reviewed the records of 21 cases of unexpected
death in people with excited delirium, which were investigated by the Office of
the Chief Coroner for Ontario between 1988 and 1995. Eyewitness testimony,
findings during postmortem examinations, clinical history, toxicological data and
other official documents describing the events surrounding the deaths were
analyzed. Specific reference was made to documented eyewitness testimony of
restraint method, body position and use of capsicum oleoresin (pepper) spray.
Because cocaine was detected in the blood of some of these people during the
postmortem examination, the role of cocaine in excited delirium was examined by
comparing the cocaine levels in these cases with levels in 2 control groups: 19
people who died from acute cocaine intoxication and 21 people who had used
cocaine shortly before they died but who had died from other causes. RESULTS: In
all 21 cases of unexpected death associated with excited delirium, the deaths
were associated with restraint (for violent agitation and hyperactivity), with
the person either in a prone position (18 people [86%]) or subjected to pressure
on the neck (3 [14%]). All of those who died had suddenly lapsed into
tranquillity shortly after being restrained. The excited delirium was caused by a
psychiatric disorder in 12 people (57%) and by cocaine-induced psychosis in 8
(38%). Eighteen people (86%) were in police custody when they died. Four (19%)
had been sprayed with capsicum oleoresin, and heart disease was found in another
4 at autopsy. The blood level of cocaine in those whose excited delirium was
cocaine induced was similar to levels found in recreational cocaine users and
lower than levels found in people who died from cocaine intoxication.
INTERPRETATION: Restraint may contribute to the death of people in states of
excited delirium, and further studies to test this hypothesis are recommended.
Meanwhile, law enforcement authorities and others should bear in mind the
potential for the unexpected death of people in states of excited delirium who
are restrained in the prone position or with a neck hold.
PMID- 9645174
TI - Death by restraint.
PMID- 9645175
TI - How do we interpret the results of the Breast Cancer Prevention trial?
PMID- 9645176
TI - Tamoxifen and breast cancer prevention: what should you tell your patients?
PMID- 9645177
TI - Unconventional therapies for cancer: 6. 714-X. Task Force on Alternative
Therapeutic of the Canadian Breast Cancer Research Initiative.
PMID- 9645178
TI - Preventing disability from work-related low-back pain. New evidence gives new
hope--if we can just get all the players onside.
AB - Despite the publication in the mid-1990s of comprehensive practice guidelines for
the management of acute low-back pain, both in the United States and elsewhere,
this ubiquitous health problem continues to be the main cause of workers'
compensation claims in much of the Western world. This paper represents a
synthesis of the intervention studies published in the last 4 years and is based
on a new approach to categorizing these studies that emphasizes the stage or
phase of back pain at the time of intervention and the site or agent of the
intervention. Current thinking suggests that medical management in the first 3-4
weeks after the onset of pain should be generally conservative. Several studies
of rather heterogeneous interventions focusing on return to work and implemented
in the subacute stage (3-4 to 12 weeks after the onset of pain) have shown
important reductions in time lost from work (by 30% to 50%). There is substantial
evidence indicating that employers who promptly offer appropriately modified
duties can reduce time lost per episode of back pain by at least 30%, with
frequent spin-off effects on the incidence of new back-pain claims as well.
Finally, newer studies of guidelines-based approaches to back pain in the
workplace suggest that a combination of all these approaches, in a coordinated
workplace-linked care system, can achieve a reduction of 50% in time lost due to
back pain, at no extra cost and, in some settings, with significant savings.
PMID- 9645179
TI - The days that will still be mine.
PMID- 9645180
TI - Just when you thought it was safe to eat a burger....
PMID- 9645181
TI - Does Canada face a crisis? US considers ending plasma exports.
AB - A shortage of intravenous immunoglobulin has caused the US to question its
exports of plasma. Since Canada relies on these exports to provide 60% of its
plasma, closing the borders could have serious consequences.
PMID- 9645182
TI - "I won't do surgery if you don't try to do my job," head of new blood agency
tells MDs. Interview by Anne Mullens.
AB - Ken Fyke is known as a tough administrator, and he is going to need all of his
administrative tricks as first chair of Canadian Blood Services, the new national
organization that is taking over responsibility for the nation's blood supply
from the Red Cross come September. Fyke says he hopes to work closely with
physicians, but they will have to realize where their responsibilities end and
his begin.
PMID- 9645183
TI - MDs who need psychiatric help afraid to seek it, conference told.
PMID- 9645184
TI - [Individually dosed levothyroxine with 150 micrograms iodide versus 100
micrograms levothyroxine combined with 100 micrograms iodide. A randomized double
blind trial].
AB - BASIC PROBLEM AND OBJECTIVE: Intrathyroid deficiency and the influence of thyroid
stimulating hormone (TSH) are the main pathogenetic factors in the development of
endemic euthyroid goitre. Goitre reduction is achieved with either administration
of levothyroxine, which diminishes hypophyseal TSG production, or of iodide. Aim
of this study was to compare the efficacy of treatment with a dose-fixed
combination of levothyroxine plus iodide with that of an individualized dosage of
levothyroxine plus iodide. PATIENTS AND METHODS: After randomization 49 patients
with euthyroid goitre (24 women, 25 men, aged 20-43 years) were treated for 12
weeks in a double-blind trial. Patients in group A received levothyroxine in a
weight-adapted dosage (75,100 or 150 micrograms) plus 150 micrograms iodide,
while those in group B were given a fixed dosage of 100 micrograms levothyroxine
plus 100 micrograms iodide. Basal TSH, thyroid hormones, iodide excretion,
hyperthyroid score and sonographic volume of the thyroid were determined before
treatment and after 12 weeks. RESULTS: Basal TSH levels were reduced in both
groups (P < 0.0001), without significant difference between the two groups
(median relative change: group A 78.1%, group B 52.8%). Thyroid volume was
decreased independently of the form of treatment (P < 0.0001) (median relative
reduction: group A 37.6%, group B 30.9%; difference not significant). Iodide
excretion rose in both groups, without significant difference (group A 107%,
group B 49%). There was hardly any change of the hyperthyroid score in both
groups. There were no side effects. CONCLUSION: Both forms of medication were
equally efficacious and well tolerated in the treatment of euthyroid goitre.
PMID- 9645185
TI - [Fatal pulmonary embolism after endoscopic embolization of downhill esophageal
varix].
AB - HISTORY AND CLINICAL FINDINGS: A 79-year-old man was admitted with a history of
recent haematemesis and tarry stools. 4 years before he had undergone a subtotal
thyroidectomy for hyperthyroidism. INVESTIGATIONS: He was anaemic (haemoglobin
7.2 g/dl, haematocrit 23%). At the transition between the upper and middle third
of the oesophagus gastroscopy revealed a bleeding oesophageal varix. TREATMENT
AND COURSE: The bleeding varix was sclerosed with polidocanol. 3 erythrocyte
concentrates were administered. Massive bleeding 2 days later was controlled with
intravaricose injection of cyanoacrylate (Histoacryl). The patient died 6 weeks
later from progressive cardiovascular failure. Autopsy revealed the cause of
death as right heart failure with extensive foreign-body pulmonary emboli
identified as thrombotic material containing polymerized cyanoacrylate found in
the previously injected oesophageal varix. Also discovered was a retrosternal
goitre which had compressed the brachiocephalic vein. Cause of the "washing-out"
of the cyanoacrylate embolus from the varix into the systemic circulation was an
oesophago-varicose collateral circulation in a cranio-caudal direction; this had
been formed by the pressure of the retrosternal goitre on the brachiocephalic
vein. CONCLUSION: Cyanoacrylate injection into a varix above the lower third of
the oesophagus should only be done under strict indication. A similar risk as
that described in this case potentially exists in the treatment of acute bleeding
from a portosystemic varicose circulation.
PMID- 9645186
TI - [Erroneous intravenous injection of adrenaline].
AB - HISTORY AND CLINICAL FINDINGS: Since a car accident a 29-year-old man had been
suffering from chronic pain treated with injections of morphine and tilidine.
Because of renewed worsening of pain he went to the emergency doctor who by
mistake intravenously injected 1 mg of undiluted adrenaline. The patients
immediately collapsed and pulmonary oedema developed. INVESTIGATIONS: On
admission he was hypotensive (85/45 mmHg) and tachycardic (135/min), respiratory
rate 36/min. Moist rales were heard throughout the lung. The white cell count was
elevated and serum potassium low (3.5 mmol/l). but other routine laboratory tests
were unremarkable. TREATMENT AND COURSE: Furosemide, nitroglycerin and morphine
were injected at once and his general state improved over the subsequent few
hours. Chest radiogram on the next day demonstrated marked reduction of the
pulmonary oedema. CONCLUSION: To prevent similar, potentially lethal, accidents,
before every i.v. injection two persons should check the name of the drug on the
label of the vial or bottle, both on drawing up and before injecting the drug.
PMID- 9645187
TI - [Catheter ablation of atrial flutter. A dependable therapeutic procedure].
PMID- 9645188
TI - [Help for patients with multiple sclerosis: current diagnostic and treatment
possibilities in neurogenic disorders of bladder emptying].
PMID- 9645189
TI - [Fluoride treatment of osteoporosis. What is its current status?].
PMID- 9645190
TI - Early events in human myelopoiesis.
PMID- 9645191
TI - Objective malignancy grading: a review emphasizing unbiased stereology applied to
breast tumors.
AB - Low reproducibility reduces the clinical value of morphologic grading of
malignant tumors, and the replacement of subjective classification by objective
quantification has been suggested. Simple mitosis counting has been employed for
objective malignancy grading most frequently and has proved its prognostic
significance in, e.g., sarcomas and carcinomas of the breast and ovary. These and
other measurements of morphometry are, however, obtained in two dimensions only,
introducing bias due to ignorance of the fact that biologic structures are three
dimensional. Stereologic estimators are, to that end, well-suited, because they
enable the assessment of spatial structure from sections. Studies addressing the
impact of stereology in tumor pathology are the subject of the current review.
Details of estimation are provided of stereologic variables of tumor size,
numbers and densities of cancer cell nuclei and mitoses, mean size and size
variability of cancer cell nuclei and variables of tissue architecture. Besides a
description of their practical estimation the influence on variables of sampling
method, tissue processing and observer variability is assessed, and estimator
efficiency and measuring equipment is evaluated. Exemplifying the clinical
importance of objective grading, results are summarized of prognostic studies of
quantitative histopathology in women with breast cancer. It has been shown that
many stereologic estimators are applicable to ordinary histologic sections
processed under routine conditions. If a systematic random scheme of sampling is
employed then the efficiency of estimation is usually high, and reproducible,
accurate and representative results are ensured. For objective malignancy grading
of breast cancer especially the volume-weighted mean nuclear size, vv (nuc),
seems valuable, and the variable usually provides independent information to that
of staging parameters. The prognostic value of vv (nuc) seems greatest in lymph
node positive subsets, whereas the importance in lymph node negative patients
should be further investigated. The clinical significance of some stereologic
variables may be restricted due to relatively time consuming measurement
procedures. However, the unbiased technique may provide precise measures of basic
parameters like "tumor burden" and tumor growth pattern, and thereby be highly
useful in experimental oncology. In conclusion, stereology is of great value for
quantifying tumor elements. For objective malignancy grading especially
assessment of the three-dimensional mean nuclear size seems useful. Prognostic
significance of this variable has been demonstrated in, e.g., malignant melanoma
and carcinomas of the breast, lung, bladder, prostate and uterine cervix. To
determine the real clinical value of the measurements, further evaluation in a
routine setting is necessary. In case such prospective studies confirm previous
findings, the future replacement of subjective grading techniques by
reproducible, objective variables seems feasible.
PMID- 9645192
TI - Differences in virus receptor for type I and type II feline infectious
peritonitis virus.
AB - Feline infectious peritonitis viruses (FIPVs) are classified into type I and type
II serogroups. Here, we report that feline aminopeptidase N (APN), a cell-surface
metalloprotease on the intestinal, lung and kidney epithelial cells, is a
receptor for type II FIPV but not for type I FIPV. A monoclonal antibody (MAb) R
G-4, which blocks infection of Felis catus whole fetus (fcwf-4) cells by type II
FIPV, was obtained by immunizing mice with fcwf-4 cells which are highly
susceptible to FIPV. This MAb also blocked infection of fcwf-4 cells by type II
feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible
gastroenteritis virus (TGEV). On the other hand, it did not block infection by
type I FIPVs. MAb R-G-4 recognized a polypeptide of relative molecular mass 120
130 kDa in feline intestinal brush-border membrane (BBM) proteins. The
polypeptide possessed aminopeptidase activity, and the first 15 N-terminal amino
acid sequence was identical to that of the feline APN. Feline intestinal BBM
proteins and the polypeptide reacted with MAb R-G-4 (feline APN) inhibited the
infectivity of type II FIPV, type II FECV, CCV and TGEV to fcwf-4 cells, but did
not inhibit the infectivity of type I FIPVs.
PMID- 9645193
TI - Dissociation of ligand-induced internalization of CXCR-4 from its co-receptor
activity for HIV-1 Env-mediated membrane fusion.
AB - The C-terminal cytoplasmic tail of chemokine receptors is important for their
internalization upon ligand binding. We generated several deletion mutants of the
C-terminal cytoplasmic tail of CXCR-4, a co-receptor for T cell line tropic
strains of human immunodeficiency virus type 1 (HIV-1), to know whether or not co
receptor internalization is associated with HIV-1 entry. Our data showed that the
removal of C-terminal 15 amino acid residues of the cytoplasmic tail from CXCR-4
completely abolished its internalization, but did not affect the co-receptor
activity at all. Co-receptor activity was fully retained even when all 45 amino
acid residues in the C-terminal cytoplasmic tail had been deleted. These data
indicated that no cytoplasmic tail nor internalization of CXCR-4 is required for
its co-receptor activity for HIV-1 entry.
PMID- 9645194
TI - Characterization of the UL16 gene product of herpes simplex virus type 2.
AB - We have raised rabbit polyclonal antisera against a His-tagged herpes simplex
virus type 1 (HSV-1) UL16 fusion protein, one of which very specifically reacted
with 40 kDa and 41 kDa proteins in the lysates of HSV-1 and HSV-2-infected cells,
respectively. Since its reactivity to the 41 kDa protein was clearly eliminated
by pre-adsorption with E. coli lysates expressing the UL16 fusion protein, the
antiserum was used to characterize the UL16 products of HSV-2. The HSV-2 UL16
protein was produced at the late phase of infection in a manner highly dependent
on viral DNA synthesis and was distributed in both the nuclei and the cytoplasma
of infected cells. In immunofluorescence studies, the UL16-specific fluorescence
in the nuclei was shown to be detected as small discrete granules. On the other
hand, the cytoplasmic fluorescence was diffusely distributed around the nucleus
at 8 h postinfection but, at later times of infection, it was mainly detected as
a mass at a perinuclear region. The analysis on its association with capsids has
revealed that the UL16 protein copurified with C capsids but not B and A capsids,
and that the association with C capsids was not tight. Moreover, our experiments
have shown that a detectable level of the UL16 protein was not associated with
extracellular virions, and that the partially purified UL16 proteins had a DNA
binding activity. These observations are consistent with the hypothesis that the
UL16 protein plays a role in capsid maturation including DNA packaging/cleavage.
We have also determined the complete nucleotide sequence of the HSV-2 UL16 gene
and found that a nonstandard initiation codon may be used for its translation.
PMID- 9645195
TI - Slight difference in primary amino acid sequence of p17 matrix protein of HIV-1
exerts profound influence on its antigenicity.
AB - HIV-1 p17 antigen has been studied for its biological significance in vitro as
well as its immunological roles in vivo. By immunological approach of antibody
binding to HIV-1 p17 antigens of several subtypes in combination with
computerized analysis of those tertial structures, it became evident that,
irrelevant of similarity of linear amino acid sequence of different HIV-1
subtypes, a few amino acid substitutions close to or distant from specified
epitope(s) affected their tertial structure resulting in change in ability of its
binding to selected antibody. ELISA employing two monoclonal antibodies, A144 and
C415, could detect p17 of subtypes A and B, but not of subtypes C, D, and E.
Since the epitope site corresponding to A144 has been reported to be important
for biological activity of p17 of HIV-1, change in tertial structure around this
epitope may explain some difference in biology of HIV-1, such as infectivity of
subtypes B and E.
PMID- 9645196
TI - Direct sequencing of the HA gene of clinical equine H3N8 influenza virus and
comparison with laboratory derived viruses.
AB - Equine influenza viruses propagated in the laboratory in alternate hosts such as
embryonated hens' eggs or mammalian cell culture have been analysed by HA
sequencing and antigenically and their sequence compared to the original virus
present in clinical material. In contrast to clinically derived human influenza
virus which generally grows in MDCK cells without change, the data for equine
influenza virus were less clear in that variants of equine virus were derived in
both eggs and cells. The study indicated that the current use of eggs for equine
influenza virus surveillance and vaccine production is entirely appropriate, but
that care should be exercised when equine influenza vaccines are produced in eggs
or on mammalian cell cultures.
PMID- 9645197
TI - Ceratobium mosaic potyvirus: another virus from orchids.
AB - A potyvirus, which we call ceratobium mosaic virus, has been detected in about
one third of more than 100 plants representing c. 33 orchid genera in two
collections in Australia. It was detected using RT-PCR with redundant primers
that are Potyviridae-specific and have additional sequences corresponding to
either the SP6 or T7 bacteriophage promoters at their 5'-termini. Thus the
nucleotide sequence of the resulting PCR fragments, consisting of about 1.7 kb of
the 3' portion of the viral genome, could be determined directly. Viral sequences
obtained from five infected orchids indicate that they contained different
isolates of a single potyvirus species most closely related to the bean common
mosaic group of potyviruses, but clearly distinct from all whose virion protein
genes have been reported to the international gene sequence databases.
PMID- 9645198
TI - Fowl adenovirus recombinant expressing VP2 of infectious bursal disease virus
induces protective immunity against bursal disease.
AB - The right hand end Nde I fragment 3 (90.8-100 map units) of the fowl adenovirus
serotype 10 (FAV-10) was characterised so as to allow the location of an
insertion site for recombinant vector construction. Infectious bursal disease
virus (IBDV) VP2 gene from the Australian classical strain 002/73, under the
control of the FAV-10 major late promoter/leader sequence (MLP/LS) was inserted
into a unique Not I site that was generated at 99.5 map units. This recombinant
virus was produced without deletion of any portion of the FAV-10 genome. When
administered to specific pathogen free (SPF) chickens intravenously,
intraperitoneally, subcutaneously or intramuscularly, it was shown that the FAV
10/VP2 recombinant induced a serum VP2 antibody response and protected chickens
against challenge with IBDV V877, an intermediate virulent classical strain.
Birds were not protected when the recombinant was delivered via the conjunctival
sac.
PMID- 9645199
TI - Membrane association and RNA binding of recombinant hepatitis A virus protein 2C.
AB - The direct function of hepatitis A virus (HAV) protein 2C, a putative NTPase, is
not known, yet genetic evidence obtained from chimeric viruses carrying the 2C
genomic region of different HAV variants indicates that it plays a pivotal role
in viral replication. In a first assessment of its potential function(s),
membrane and RNA binding properties of HAV 2C were studied after expressing the
protein in various recombinant systems. In contrast to poliovirus 2C, expression
of HAV 2C was inhibitory to the growth and protein synthesis of bacteria.
Deletion of the N-terminal amphipathic helix of 2C abrogated this effect and the
ability of 2C to associate with eukaryotic membranes. Both, purified 2C and the N
terminally truncated protein were shown to bind RNA in vitro. Our data taken
together suggest that HAV 2C is a multifunctional protein.
PMID- 9645200
TI - Cassava vein mosaic virus (CsVMV), type species for a new genus of plant double
stranded DNA viruses?
AB - The complete sequence of 8159 nucleotides of the double stranded DNA genome of
cassava vein mosaic virus (CsVMV) was determined (# U59751) and revealed a
significant difference in genome organization when compared with a previous
report (# U20341). When transferred to cassava plants by microbombardment, the
full length CsVMV clone was infectious, confirming the genome organization here
described. Sequence comparisons between CsVMV and members of the genera
Caulimovirus and Badnavirus revealed high homologies between consensus sequences
of several proteins that are indispensable for virus replication, including a
potential transactivator factor not reported previously. The presence of a
sequence complementary to a plant Met tRNA confirms that CsVMV is a plant
pararetrovirus and is most closely related to members of the genus Caulimovirus
as previously assessed. However, differences in genome organization, number and
size of the ORFs, in addition to sequence comparisons with other plant
pararetroviruses, shows that either the genetic variability of caulimoviruses is
much greater than previously thought, or that CsVMV is the unique representative
of a new genus within the Caulimoviridae family. On the basis of this study, it
is proposed to upgrade the floating genus Caulimovirus to the family level and to
divide the Caulimoviridae family into at least three genera with CsVMV being the
type member of a new genus.
PMID- 9645201
TI - Characterization of Trichomonas vaginalis virus proteins in the pathogenic
protozoan T. vaginalis.
AB - The 4.6-kb double-stranded (ds) RNA of Trichomonas vaginalis virus (TVV)-T1 has
been shown to encode two overlapping genes, cap and pol. In this study, a serum
for specifically detecting viral cap gene product was raised against a
recombinant protein, and sera for specifically detecting pol gene product were
raised against synthetic oligopeptides. A 75-kDa major protein and a 160-kDa
minor protein were detected by anti-CAP serum in a TVV-T1 sample, indicating that
the 75-kDa protein is the viral capsid protein. The 160-kDa protein alone was
also detected by two distinct anti-POL sera, indicating that the pol gene is
expressed as a CAP-POL fusion protein. These results suggest that the TVV-T1
genome is arranged into a cap-pol organization in a manner similar to that of
viruses in family Totiviridae.
PMID- 9645202
TI - Citrus viroid Ia is a derivative of citrus bent leaf viroid (CVd-Ib) by partial
sequence duplications in the right terminal region.
AB - Nucleotide sequences of group I citrus viroids Ia (CVd-Ia) and citrus bent leaf
viroid (CBLVd, formerly designated CVd-Ib) isolated from citrus plants in Japan,
the Philippines and China have been determined. Citrus samples in Japan and the
Philippines contained CVd-Ia, which consists of 328 nucleotides(nt). Although 10
nt longer than the type CBLVd-225A in Israel they share 94% identity in overall
nucleotide sequence. The Philippines sample also contained a 329-nt long CVd-Ia
sequence variant, in which one base insertion and three substitutions were
observed. A citrus in China contained CBLVd, which consists of 318 nt and shares
98% identity to CBLVd-225A. CVd-Ia was clearly separated from CBLVd by two 5-nt
insertions located in upper (5'-AGCUG-3') and the lower (5'-CUUCU-3') strand of
the right terminal region (which is also designated T2 domain) in rod-like
secondary structure. Since both of the additional 5-nt sequences are similar to
the adjacent sequences (5'-AGUUG-3' and 5'-CUUCU-3'), we hypothesize that CVd-Ia
is a derivative of CBLVd caused by partial sequence duplications and
substitutions taking place in the right terminal region.
PMID- 9645203
TI - In vivo interactions among rotavirus nonstructural proteins.
AB - The rotavirus genome encodes six nonstructural (NS) proteins, five of which
(NSP1, NSP2, NSP3, NSP5, and NSP6) have been suggested to be involved in a
variety of events, such as genome replication, regulation of gene expression, and
gene assortment. These NS proteins have been found to be associated with
replication complexes that are precursors of the viral core, however, little
information is available about the intermolecular interactions that may exist
among them. Using the yeast two-hybrid system, which allows the detection of
protein-protein interactions in vivo, all possible combinations among the
rotavirus NS proteins were tested, and several interactions were observed. NSP1
interacted with the other four proteins tested; NSP3 associated with itself; and
NSP5 was found to form homodimers and to interact with NSP6. Co
immunoprecipitation of proteins from rotavirus-infected cells, using hyperimmune
sera monospecific for the NS proteins, showed the same interactions for NSP1 as
those observed in yeast. Immunofluorescence co-localization analysis of virus
infected epithelial cells revealed that the intracellular distribution of
proteins that were seen to interact in yeast had patterns of distribution that
would allow such intermolecular interactions to occur. These findings should
contribute to the understanding of the role these proteins play in different
aspects of the virus replication cycle.
PMID- 9645204
TI - Protective efficacy of a dengue 2 DNA vaccine in mice and the effect of CpG
immuno-stimulatory motifs on antibody responses.
AB - A recently described DNA vaccine for dengue (DEN) type 2 was shown to elicit high
levels of neutralizing antibodies in mice. The vaccine candidate consists of the
PreM and 92% of the envelope genes of DEN 2 New Guinea C strain. We further
evaluated this DNA vaccine candidate by examining the effect of immuno
stimulatory CpG DNA motifs on antibody response and by studying the protective
efficacy of the vaccine. The results showed that CpG motifs present in pUC 19
significantly improved the antibody response to a suboptimal dose of 3.1
micrograms of the DEN DNA vaccine. In a lethal mouse intracerebral challenge
model, the vaccine provided a significant level of protection. Sixty percent of
the mice immunized with the DEN DNA vaccine plus pUC 19 survived the challenge
compared to only 10% in the control group that received vector plus pUC. These
studies illustrate that nucleic acid immunization is a viable approach to
developing a DEN vaccine and that immuno-stimulatory CpG DNA motifs can be used
to lower the minimum dose required to produce an antibody response.
PMID- 9645205
TI - Comparison of the coat protein, movement protein and RNA polymerase gene
sequences of Australian, Chinese, and American isolates of barely yellow dwarf
virus transmitted by Rhopalosiphum padi.
AB - Barely yellow dwarf luteovirus-GPV (BYDV-GPV) is a common problem in Chinese
wheat crops but is unrecorded elsewhere. A defining characteristic of GPV is its
capacity to be transmitted efficiently by both Schizaphis graminum and
Rhopaloshiphum padi. This dual aphid species transmission contrasts with those of
BYDV-RPV and BYDV-SGV, globally distributed viruses, which are efficiently
transmitted only by Rhopaloshiphum padi and Schizaphis graminum respectively. The
viral RNA sequences encoding the coat protein (22K) gene, the movement protein
(17K) gene, the region surrounding the conserved GDD motif of the polymerase gene
and the intergenic sequences between these genes were determined for GPV and an
Australian isolate of BYDV-RPV (RPVa). In all three genes, the sequences of GPV
and RPVa were more similar to those of an American isolate of BYDV-RPV (RPVu)
than to any other luteovirus for which there is data available. RPVa and RPVu
were very similar, especially their coat proteins which had 97% identity at the
amino acid level. The coat protein of GPV had 76% and 78% amino acid identity
with RPVa and RPVu respectively. The data suggest that RPVu and RPVa are
correctly named as strains of the same serotype and that GPV is sufficiently
different from either RPV strain to be considered a distinct BYDV type. The coat
protein and movement protein genes of GPV are very dissimilar to SGV. The
polymerase sequences of RPVu, RPVa and GPV show close affinities with those of
the sobemo-like luteoviruses and little similarity with those of the carmo-like
luteoviruses. The sequences of the coat proteins, movement proteins and the
polymerase segments of BYDV serotypes, other than RPV and GPV, form a cluster
that is separate from their counterpart sequences from dicot-infecting
luteoviruses. The RPV and GPV isolates consistently fall within a dicot-infecting
cluster. This suggests that RPV and GPV evolved from within this group of
viruses. Since these other viruses all infect dicots it seems likely that their
common ancestor infected a dicot and that RPV and GPV evolved from a virus that
switched hosts from a dicot to a monocot.
PMID- 9645206
TI - Coat protein sequence of Krish-infecting strain of Johnsongrass mosaic potyvirus.
AB - The morphology of an Australian strain of Johnsongrass mosaic potyvirus (JGMV
Krish-infecting strain), capable of infecting sorghums carrying the Krish
potyvirus resistance gene, was investigated and the base sequence of the coat
protein region determined. Under the electron microscope the virus was
indistinguishable from the wild type prevalent in Australia, JGMV-Jg. However,
there were some significant changes in the inferred amino acid sequence in both
the N-terminus and the core regions of the coat protein. Some of these amino acid
changes may be responsible for breaking the resistance of sorghums carrying the
Krish virus resistance gene. In the discussion mention is made of a preliminary
result with a mutated in vitro transcript which supports this suggestion.
PMID- 9645207
TI - Molecular and immunologic characterization of group A bovine rotavirus field
isolates with P8[11] spike protein.
AB - Bovine rotavirus strain B223 is the North American prototype for group A P8[11]
serotype/genotype rotaviruses. Rotaviruses with this serotype/genotype are a
prevalent cause of neonatal calf diarrhea and have also been isolated from
asymptomatic human infants. On the basis of deduced amino acid sequence of the
outer capsid viral protein 4 (VP4), strain B223 lacks a cysteine at position 318
that is conserved among all other rotavirus strains. It has been speculated that
this may result in the loss of disulfide bond and a change in the structure of
the VP4 that may affect the infectivity and antigenicity of the virus. This paper
describes partial sequences of the VP4 gene (nucleotides 613 to 1016 coding for
amino acid positions 202 to 335) of 16 bovine rotavirus field isolates with
P8[11] that were obtained from calves in Nebraska and Indiana. All the isolates
lack a cystein at position 203 and had a conserved valine residue at position
318, thus indicating that the prototype strain B223 is representative of group A
rotaviruses with P8[11] serotype/genotype.
PMID- 9645208
TI - HTLV-1 in mouthwash cells from a TSP/HAM patient and asymptomatic carriers.
AB - Using in situ hybridization, the presence of T-cell lymphotrophic virus type I
(HTLV-I) was shown in blood lymphocytes of one tropical spastic paraparesis
(TSP/HAM) patient and in two asymptomatic carriers. HTLV-I was also detected in
epithelial cells derived from mouthwash of the TSP/HAM patient. Mouthwash of one
of the carriers showed an infected lymphocyte while mouthwash of the other
carrier was negative. The infected epithelial cells stained both in the nucleus
and in the cytoplasm, which indicated the presence of the virus in both
subcellular compartments. Our observations suggest that saliva cells, lymphocytes
and epithelial cells, may potentially participate in oral transmission of HTLV-I.
PMID- 9645209
TI - [Proliferation and apoptosis before and after preoperative simultaneous
radiochemotherapy of rectal carcinomas].
AB - PURPOSE: To investigate the relationship between apoptotic cell death,
proliferative activity, and the status of the tumor suppressor gene p53 in rectal
cancer before and after radiochemotherapy. MATERIALS AND METHODS: Thirty-two
patients dispositioned to receive preoperative radiochemotherapy for locally
advanced rectal carcinoma prior to radical surgical tumor resection were
analysed. In all cases, pretherapy biopsies and the final resected specimens
after radiochemotherapy were available for analyses. Apoptotic cells were
identified and quantified using in situ end labeling (ISEL) technique. The
proliferative activity was determined by immunohistochemical assessment of the
Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well.
A clinical-to-pathologic downstaging after radiochemotherapy was achieved in
25/32 patients (78%). In one case, no residual tumor was detected after
radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index
increased significantly in almost every case examined. In contrast, the
proliferative activity was significantly decreased when comparing biopsies and
resected specimens. Tumors that were immunohistochemically negative for p53
generally exhibited a higher apoptotic index than p53 positive tumors. However,
we did not find any correlation between the (pre- and post-therapeutic) rate of
apoptosis and the degree of clinical-to-pathologic downstaging. CONCLUSION: Our
results indicate, that radiochemotherapy induces an increase in apoptotic cell
death. The observation of higher rates of apoptosis in p53 negative tumors
suggests that p53 might be a regular of apoptosis in rectal cancer.
PMID- 9645211
TI - [Predictive significance of reflex otalgia in local radical radiotherapy of
oropharyngeal carcinomas].
AB - BACKGROUND: Patients with carcinomas of the upper aero-digestive tract often
suffer from ear pain as a tumor associated syndrome. This prospective study
examines the predictive and prognostic value of this symptom. PATIENTS AND
METHODS: Ninety-six consecutive patients who completed a locally radiotherapy of
a carcinoma of the oropharynx were prospectively evaluated and followed. Forty
nine out of 96 patients stated the symptom, either spontaneously or after
questioning. The 2 groups showed no difference regarding TNM-classification,
histology and total dose. Overall survival, local control and disease specific
survival were calculated according to Kaplan-Meier and compared by the log-rank
test. RESULTS: A clinically complete remission was obtained in significantly
fewer patients with reflex-otalgia as compared to patients without reflex
otalgia, 61.2% versus 89.3%, p < 0.002. Local control of patients with reflex
otalgia was significantly less with 49%, mean follow-up 564 days, in comparison
to local control in patients without reflex-otalgia, mean follow-up 613 days, p =
0.01. Disease specific survival was significantly worse for patients with reflex
otalgia, p < 0.012. The probability of local control of T1/T2 tumors with reflex
otalgia was similar to T3/T4 tumors without reflex-otalgia. Local control for all
tumor categories combined is 74% for patients without reflex-otalgia versus 49%
for patients with reflex-otalgia. CONCLUSION: In our patients, reflex-otalgia is
a new and statistically significant parameter for the probability of local
control and disease specific survival.
PMID- 9645210
TI - [Treatment of stage IIIB loco-regionally advanced non-small-cell bronchial
carcinomas with radiation and interferon-beta. Preliminary results of a phase II
study].
AB - BACKGROUND: In-vitro and in-vivo studies demonstrated the radiosensitizing effect
of interferon beta on malignant tumor tissue as well as simultaneously a
radioprotective effect on normal lung tissue. In this phase II study the outcome
of combining radiotherapy with interferon beta in patients with advanced non
small cell lung cancer was evaluated. PATIENTS AND METHOD: From February 1994
until November 1996 14 patients with non-small cell lung cancer, stage IIIB were
treated with locoregional radiation up to 59.4 Gy, with daily doses of 1.8 Gy and
5 fractions per week. Five million units of interferon beta (Fiblaferon) were
given intravenously immediately preceding radiotherapy on the first 3 days of
week 1, 3 and 5. RESULTS: Four of 14 patients (28.6%) showed complete response
and 7 patients (50%) partial response, resulting in an overall response rate of
78.6%. After a mean follow-up time of 23.3 months the 1-, 2- and 3-year survival
rates were 56.3%, 37.5% and 37.5%, respectively. The median survival time was 13
months. Three of 14 patients (21.4%) suffered from 7 Grade-3 acute side effects
and 2 patients (14.3%) from 1 Grade-3 late toxicity in each case. One further
patient, whose right lung was resected 3 months after completion of radiotherapy,
developed as a consequence of this operation 2 Grade-4 complications. CONCLUSION:
Considering the toxicity and the preliminary results of combining irradiation and
interferon beta in the treatment of locally advanced non-small cell lung cancer
it seems, that this procedure is worth to be tested in a phase III study.
PMID- 9645212
TI - [Primary radiotherapy of recurrent Merkel cell carcinoma of the eyelid. Case
report and review of the literature].
AB - BACKGROUND: Despite an increasing number of reports Merkel-cell-carcinoma still
is a rare neoplasm. Reports on radical radiotherapy are sparse. PATIENT AND
METHOD: We report on a successful radical radiotherapy of a recurrent Merkel-cell
carcinoma of the eyelid in an 84-year old woman, using a hypofractionated
treatment of 50 Gy with 70 kV-X-rays, 10 fractions of 5 Gy within 5 weeks.
RESULT: Rapid and complete remission was achieved, with no signs of local or
distant failure 24 months after the end of therapy. CONCLUSION: The case reported
on highlights the radiosensitivity of this tumor and the role of radiotherapy not
merely as salvage procedure.
PMID- 9645213
TI - Comparison of the response of human FaDu squamous cell carcinoma in nude mice
after hypofractionated-accelerated regimens and "curative" fractionation
schedules.
AB - BACKGROUND: It has been suggested that tumors respond differently after
irradiation with 10 or more fractions than with less fractionated regimens and
that extrapolation from experiments with only a few fractions to "curative"
regimens may be invalid. To test this hypothesis, we compared hypofractionated
accelerated treatments with "curative" fractionation schedules in human squamous
cell carcinoma in nude mice. MATERIAL AND METHODS: FaDu tumors were transplanted
subcutaneously into the hindleg of NMRI nu/nu mice. TCD50 values, i.e., the dose
necessary to control 50% of the tumors locally, were determined after irradiation
under ambient blood flow conditions with 5 and 10 fractions in 5 days, 10
fractions in 10 days, and 30 fractions in 15 days, 6 weeks or 10 weeks. RESULTS:
TCD50 values of the hypofractionated regimens were not significantly different
and varied from 41 to 46 Gy. The number of fractions given in the same overall
time had no measurable effect on local tumor control. The TCD50 after 30
fractions in 6 weeks was 30 Gy higher than after the hypofractionated regimens.
This effect was caused by a substantial increase of TCD50 with overall treatment
time, the dose recovered per day was 0.82 Gy (95% CI 0.66; 0.96). alpha/beta eff
determined from all data was 58 Gy (13; infinite). CONCLUSIONS: The results of
the present study compare well with our previous findings after different
"curative" fractionation schedules in the same tumor. Thus, our study does not
support that tumors respond differently after application of 10 or more fractions
compared to less fractionated regimens. The biological mechanisms that govern the
radiation response of FaDu tumors appear to be the same for hypofractionated
accelerated and "curative" regimens. Since only one tumor was investigated, these
results cannot be generalized at the present time.
PMID- 9645214
TI - [Analysis of different application systems and CT-controlled planning variants in
treatment of primary endometrial carcinomas. Is brachytherapy treatment of the
entire uterus technically possible?].
AB - BACKGROUND: Intracorporal brachytherapy is regarded as the definitive component
of treatment for inoperable patients with endometrial carcinoma. Until now the
whole uterus has been claimed to represent the target volume independent of
individual tumor spread. The purpose of this work is to analyse the correlation
between target volume and treated volume using different application- and
planning procedures. PATIENTS AND METHODS: In a consecutive series of 10 patients
with primary irradiated endometrial carcinoma we analyzed the correlation between
target volume and treated volume using either standard 1-channel applicators or
individual Heyman-applicators. Application of the ovoids was followed by a
planning CT scan for all patients. Based on this, target volume (uterus volume)
was estimated on a 3D-planning system. According to the measurable length of the
uterus cavity we determined the corresponding standard 1-channel applicator and
calculated the respectively treated volume. Estimating the advantages of an
optimized treatment planning strategy for individual Heyman-applications were
compared the treated volumes, which result from a standardized and optimized
treatment planning procedure. RESULTS: The mean uterus volume was 180 cm3 (range
57 to 316 cm3). Asymmetric uterus configurations with longitudinal or sagittal
side differences exceeding 1 cm were found in 40% of the cases. Using standard 1
channel applicators on average 47% (range 25 to 89%) of the uterus volume were
enclosed by the treated volume compared to 70% for Heyman-applications.
Differentiating these individual applications according to the variable treatment
modality values of mean 66% (range 36 to 110%) for the standardized and 73%
(range 48 to 95%) for the optimized treatment planning strategy were found.
Moreover optimized planning modalities led to an improved coverage of the target
volume in 5 out of 10 cases with an increase in volume of 20% on average (range
11 to 32%). In 3 cases changes of less than 5% were noticed (no improvement). In
order to protect organs at risk treated volume had to be decreased in 2 cases for
19% and 40% respectively. CONCLUSIONS: Intracavitary brachytherapy of primary
endometrial carcinoma was improved by individualized application- and planning
procedures, which led to better adaptations of the treated volumes to the target
volumes. Nevertheless a complete coverage--corresponding to the primary intent-
was not possible. Individualized and optimized brachy-therapy must be performed
according to the individual tumor spread and uterus configuration. Therefore,
different applicators are required.
PMID- 9645215
TI - [Dose-volume histograms and 3-D planning in breast-saving therapy of breast
carcinoma].
AB - AIM: Improvement of the dose homogeneity in radiation treatment of the intact
breast using 3D-planning and dose volume histograms. PATIENTS AND METHOD: 3D
planning, including the calculation of dose volume histograms of the planning
target volume, was performed on 15 patients, who underwent radiation therapy with
tangential photon beams. A standard plan and 2 modified or optimized plans were
evaluated. Different dosimetric parameters like maximum dose, mean dose, standard
deviation and the fractional volume which receives doses from 95 to 105% of the
reference dose were compared and correlated with breast size. RESULTS: With
increasing breast size standard planning leads to increased overdosage, both in
magnitude and volume. Individual optimization by modifying weights and wedges
gives no improvement in dose homogeneity, whereas a photon energy of 10 MV
results in a more homogeneous dose distribution. The drawback of the higher
energy is the increased underdosage of the skin. CONCLUSION: Using the standard
geometry of tangential fields the dose homogeneity cannot be improved
significantly by 3D-planning, compared to our standard technique.
PMID- 9645216
TI - [Oral sucralfate administration for therapy and prevention of radiation-induced
esophagitis: results of a placebo-controlled double-blind study].
PMID- 9645217
TI - [Late toxicity after allogeneic bone marrow transplantation in children in
relation to conditioning regimen: whole body irradiation versus busulfan].
PMID- 9645218
TI - [Alternating radiochemotherapy in bladder carcinomas].
PMID- 9645219
TI - [Anti-angiogenetic therapy of tumors in the animal experiment].
PMID- 9645220
TI - Retrotransposable elements in the Dictyostelium discoideum genome.
AB - Repetitive DNA is a major component of any living cell. In eukaryotes
retrotransposable elements make up several percent of the genome size, and
consequently, retroelements are often identified in experiments aimed at
establishing physical maps and whole genome sequences. In this review, recent
progress in the characterization of retrotransposable elements in the genome of
the eukaryotic microorganism Dictyostelium discoideum is summarized with a focus
on retroelements which integrate near transfer RNA genes with intriguing position
specificity.
PMID- 9645221
TI - Screening of conformationally constrained random polypeptide libraries displayed
on a protein scaffold.
AB - The selection of novel proteins or enzymes from random protein libraries has come
to be a major objective in current biology, and these enzymes should prove useful
in various biological and biomedical fields. New technologies such as in vitro
selection of proteins in cell-free systems have high potential to realize
evolutionary molecular engineering of proteins. This review highlights an
application of insertional mutagenesis of proteins to evolutionary molecular
engineering. Random sequence proteins are inserted into the surface of a host
enzyme which serves as a scaffold to display random protein libraries.
Constraints on random polypeptide conformations owing to the proximity of N- and
C-termini on the scaffold would result in greater screening efficiency of
libraries. The scaffold enzyme is also used as a probe for monitoring the hill
climbing of random sequence proteins on a fitness landscape and navigating rapid
protein folding in the sequence space.
PMID- 9645222
TI - Mechanisms of resistance to xenobiotics in human therapy.
AB - Xenobiotic resistance is the major cause of failure in human therapies. Because
of their serious clinical and economical consequences, resistance phenomena have
been intensively studied in the case of antibacterial, anticancer, antipaludic
and anti-human immunodeficiency virus-1 therapies. Beside pharmacological factors
that can impede the action of the drugs, several cellular mechanisms of
resistance have been described. Surprisingly, these mechanisms are conserved
among bacteria, eucaryotic cells, parasites and viruses. The efficiency of drugs
can be circumvented by alteration of the drug cellular concentration (altered
influx, enhanced efflux or sequestration), detoxification, alteration of the drug
target, nonactivation or inactivation of the drug, or by enhanced DNA repair.
PMID- 9645223
TI - Mechanisms controlling cellular suicide: role of Bcl-2 and caspases.
AB - Apoptosis is an essential and highly conserved mode of cell death that is
important for normal development, host defense and suppression of oncogenesis.
Faulty regulation of apoptosis has been implicated in degenerative conditions,
vascular diseases, AIDS and cancer. Among the numerous proteins and genes
involved, members of the Bcl-2 family play a central role to inhibit or promote
apoptosis. In this article, we present up-to-date information and recent
discoveries regarding biochemical functions of Bcl-2 family proteins, positive
and negative interactions between these proteins, and their modification and
regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1
and stress-activated protein kinases. We have critically reviewed the functional
role of caspases and the consequences of cleaving key substrates, including
lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have
presented the latest Fas-induced signalling mechanism as a model for receptor
linked caspase regulation. Finally, the structural and functional interactions of
Ced-4 and its partial mammalian homologue, apoptosis protease activating factor-1
(Apaf-1), are presented in a model which includes other Apafs. This model
culminates in a caspase/Apaf regulatory cascade to activate the executioners of
programmed cell death following cytochrome c release from the mitochondria of
mammalian cells. The importance of these pathways in the treatment of disease is
highly dependent on further characterization of genes and other regulatory
molecules in mammals.
PMID- 9645224
TI - The structure and function of platelet-activating factor acetylhydrolases.
AB - Platelet-activating factor acetylhydrolases (PAF-AHs, EC 3.1.1.47) constitute a
unique and biologically important family of phospholipase A2s. They are related
to neither the well-characterized secretory nor cytosolic PLA2s, and unlike them
do not require Ca2+ for catalytic activity. The distinguishing property of PAF
AHs is their unique substrate specificity: they act on the phospholipid platelet
activating factor (PAF), and in some cases on proinflammatory polar
phospholipids, from which they remove a short acyl moiety--acetyl in the case of
PAF--located at the sn-2 position. Because PAF is found both in the plasma and in
the cytosol of many tissues, PAF-acetylhydrolases are equally widely distributed
in an animal organism. Recent crystallographic studies shed new light on the
complex structure-function relationships in PAF-AHs.
PMID- 9645225
TI - Drug susceptibility of PCA in WBB6F1-W/Wv mice.
AB - Our previous study revealed that passive cutaneous anaphylaxis (PCA) can be
produced in congenitally mast cell-deficient WBB6F1-W/Wv (abbreviated as W/Wv)
mice on sensitization with undiluted or slightly diluted allogeneic and
xenogeneic antisera but not on sensitization with allogeneic monoclonal
immunoglobulin (Ig)E and IgG1 antibodies regardless of the antibody concentration
[1]. In view of these findings, the present study was conducted to characterize
PCA in this strain from its drug susceptibilities using mast cell-bearing WBB6F1
(+)/+ (abbreviated as +/+) and B6D2F1 mice as references. PCA in W/Wv mice
mediated by a low dilution (1:4) of hyperimmune serum to bovine serum albumin of
the B6D2F1 mouse origin was markedly suppressed by CV-6209, an antagonist of
platelet-activating factor (PAF), but not by antihistamines such as
cyproheptadine and oxatomide. In contrast, PCA in +/+ and B6D2F1 mice mediated by
a high dilution (1:128) of the anti-serum (virtually by IgG1 antibody) was nearly
completely suppressed by antihistamines but not by CV-6209. A remarkable
difference between PCA in W/Wv and reference mice was also observed in the
susceptibility to monoclonal anti-mouse granulocyte (Gr-1) antibody: PCA in W/Wv
mice was potently suppressed by the 1- to 3-day pretreatment with this antibody
but that in references was not at all. Putting these present results together
with the previous finding that anti-granulocyte antibody greatly reduces
circulatory Gr-1+ leukocytes, 1 to 3 days after the treatment [2], it is highly
probable that PCA in W/Wv mice mediated by some antibody isotypes other than IgE
and IgG1 is produced by PAF mainly released from Gr-1+ cells, while IgG1 antibody
mediated PCA in mast cell-bearing reference mice is evoked by histamine derived
from mast cells. PCA homologous to that in W/Wv mice could also be produced in
the reference mice on sensitization with undiluted or slightly diluted antiserum,
when generalized blueing due to excess IgG1 antibody was removed by the oxatomide
treatment before the antigen challenge.
PMID- 9645226
TI - Regulation of rhythmic melatonin production in pineal cells of chick embryo by
cyclic AMP.
AB - The pineal cells of chick embryos incubated in vitro exhibited a daily rhythm of
melatonin synthesis under a 12:12 light:dark (LD) cycle at the embryonic days 16
and 19. In order to elucidate whether cyclic adenosine monophosphate (cAMP)--a
component of the melatonin generating system--is already at work in the embryonic
period, we measured the effects of forskolin and isobuthylmethylxantine (IBMX) on
melatonin production, cAMP efflux and accumulation. Forskolin (after 10, 20, 30,
45, 60 and 90 min of administration) and IBMX (6 h), when applied during the
light phase of LD cycle, stimulated melatonin production and cAMP efflux and
accumulation during the embryonic period (at days 16 and 19 fo development). Our
results suggest that the biochemical pathway involving cAMP, which controls
melatonin production in the postnatal period, is developed before hatching and
already on embryonic day 19 works in a way similar to that in post-hatched
chicks. Differences in response to cAMP stimulation between 16- and 19-day-old
pinealocytes seem to be mostly quantitative.
PMID- 9645227
TI - Antimicrobial activity in the skin of the channel catfish Ictalurus punctatus:
characterization of broad-spectrum histone-like antimicrobial proteins.
AB - Three antibacterial proteins were isolated from acid extracts of channel catfish
(Ictalurus punctatus) skin by cation exchange chromatography and reverse-phase
high-pressure liquid chromatography. The molecular masses of the proteins were
15.5, 15.5 and 30 kD as determined by SDS-polyacrylamide gel electrophoresis.
Mass spectrometry, amino acid composition and amino acid sequence data suggest
that the most abundant protein is closely related to histone H2B. The H2B-like
protein was inhibitory to Aeromonas hydrophila and Saprolegnia spp., which are
important bacterial and fungal pathogens of fish. These findings suggest that
histones may be important defensive molecules in fish.
PMID- 9645228
TI - Dictyostelium discoideum cells shed vesicles with associated DNA and vital stain
Hoechst 33342.
AB - Dictyostelium discoideum cells are highly resistant to xenobiotics. We previously
observed that these primitive eukaryotic cells contain a 170-kDa P-glycoprotein,
mediating multidrug resistance in mammalian cells, but nonfunctional in
Dictyostelium cells. We show here that D. discoideum cells vitally stained with
the DNA-specific dye, Hoechst 33342, release fluorescent material in their
culture medium. Electron microscopy and lipid analysis demonstrate the vesicular
nature of this material. Moreover, nucleic acids associate with these
extracellular vesicles independently of Hoechst vital staining. The main
vesicular DNA component exhibits a size > 21 kb. Shedding of microvesicles during
cell growth is not concomitant with programmed cell death. We propose that these
extracellular vesicles are involved in a new cellular resistance mechanism
against xenobiotics. Furthermore, since the association of DNA with vesicles
occurs in physiological growth conditions and independently of vital staining,
the new shedding process might be involved in a more general intercellular
mechanism.
PMID- 9645229
TI - [Establishment of the Mendel Institute].
PMID- 9645230
TI - Bioethical considerations on cloning and twinning.
PMID- 9645231
TI - From genetic research into clinical practice.
AB - The present genome era is characterized by speedy progress and prompt transfer of
results into clinical practice. This creates the need for rapid disclosure of
results and renewal of laboratory's protocols. Molecular cytogenetics has
provided and increased ability to identify chromosomes, correlate chromosome
structure with gene location, find out cryptic aberrations, and detect specific
DNA sequences. These advances have allowed the confident discovery of a number of
contiguous gene syndromes. The positional cloning and positional candidate
strategies have greatly expedited the search process of disease genes, and become
relevant methods for genes' discovery. Understanding the molecular basis of
diseases has shown an unpredicted wide genetic heterogeneity, which has splitted
single disorders into many clinically similar conditions, and added complexity to
the nosology of human diseases. The opposite process, allelism, where clinical
diversity results from allelic mutations, has lumped together many distinct
disorders, by showing that different clinical entities are not necessarily due to
mutations in different genes. Dynamic mutations have provided the molecular
understanding of interindividual and intrafamilial variability including
anticipation, in a number of diseases. The discovery of distinct correlations
between the molecular pattern and disease severity is providing a unique
opportunity for using molecular results to assess the clinical outcome.
Diagnostic, presymptomatic and predictive molecular testing are becoming widely
used and provide enormous opportunities for improving the lot of our patients.
PMID- 9645232
TI - Twin zygosity diagnosis by mailed questionnaire below age twelve months. Le
Groupe Romulus.
AB - Parents of a sample of 76 same sexed pairs of twins aged 3 to 9 months completed
a mailed similarity questionnaire. It included the Bonnelykke et al.'s
questionnaire and a four anthropological variable scale. To improve each of these
two methods, three other combined methods were carried out and results were
compared with the biological zygosity diagnosis. The Bonnelykke et al.'s
classification combined with anthropological scale (method 4) gave only 1.2%
misclassified in the whole sample. It is concluded that zygosity diagnosis using
this type of procedure to distinguish MZ and DZ pairs would be important not only
for epidemiological study but also for pediatricians and parents.
PMID- 9645233
TI - Maternal nutrition in twin gestations: weight gain, cravings and aversions, and
sources of nutrition advice.
AB - BACKGROUND: Maternal nutrition has a strong influence on singleton and twin
birthweight. This study evaluated the association between twin birthweight and
maternal pregravid body mass index (BMI), weight gain, and cravings and
aversions. Information was also obtained regarding sources of nutrition advice
and advised versus actual weight gain. METHODS: This study is based on data from
interviews with 928 mothers of twins. Univariate analysis included comparisons by
source of nutritional advice, birthweight categories, and categories of cravings
and aversions. Multiple logistic regression was used to formulate models for mean
twin birthweights > 1,500 g and > 2,500 g. RESULTS: Mothers who received their
nutrition advice from a registered dietitian had the highest weight gains and the
lowest proportion of birthweights < 1,500 g. For mean twin birthweight > 2,500 g,
the final model included prematurity, pregravid BMI, and weight gain; for
birthweights > 1,500 g, the model additionally included maternal age and
aversions. CONCLUSIONS: Maternal pregravid BMI and gestational weight gain were
shown to be important factors influencing twin birthweight. Nutrition advice,
particularly from a registered dietitian, may be vital in assuring adequate
weight gain, and therefore better birthweights, for these high-risk pregnancies.
PMID- 9645234
TI - Very early and simple determination of chorionic and amniotic type in twin
gestations by high-frequency transvaginal ultrasonography.
AB - OBJECTIVE: The aim was to determine the chorionic and amniotic types in
multifetal pregnancies with transvaginal ultrasonography at very early stage of
gestation. STUDY DESIGN: Twenty-one spontaneous multifetal pregnancies were
scanned transvaginally before 8 weeks' gestation (four of them from 4th week).
The chorionic and amniotic type was determined ultrasonographically. All twin
gestations had postpartum pathologic evaluation of the placenta and histologic
determination of the chorionic and amniotic type. RESULTS: Ultrasonographic
evaluation of the 21 pregnancies demonstrated 20 twin and 1 triplet gestation.
Four of the twin pregnancies were monochorionic-diamniotic. Triplet was
monochorionic-triamniotic (spontaneously aborted in 8th week of gestation). In
all 20 twin pregnancies, transvaginal ultrasonography correctly predicted the
chorionic and amniotic type before 8 weeks of gestation. CONCLUSION: Transvaginal
ultrasonography allows a reliable, simple and rapid determination; the
dichorionic twin pregnancy in 4 weeks, monochorionic in 5 weeks, and
differentiation of mono- or diamniotic in 7 weeks of gestation.
PMID- 9645235
TI - Perinatal outcome after leave of absence from work for twin-pregnant women.
AB - AIM: To evaluate the association between the incidence of leave of absence from
work and perinatal outcome for the twin-pregnant woman. MATERIAL AND METHODS: A
20.2% sample of all twin-pregnant women between 1982 and 1988 (1,331/6,602) was
taken at random from the entire material of twin deliveries in Sweden, archived
at the Medical Birth Registry (MBR), National Board of Health and Welfare. For
each woman in the sample, information on period(s) and reasons for leave of
absence from work during pregnancy was obtained by inquiry to all Regional Health
Insurance Offices throughout Sweden. A comparison of perinatal outcome was also
made with information from the Danish Fertility Database and the Norwegian
Medical Birth Registry. RESULTS: Duration of leave from work increased from 58
days in 1982 to 97 days in 1988 (trend analysis; t = 7.9, p < 0.001). No
association was seen between perinatal mortality for twins weighing < 1,500 g and
changes in the incidence of leave of absence. The incidence of twins with a
birthweight < 1,500 g varied among the three countries, increasing significantly
only in Sweden (trend analysis chi 2 = 20.3, p < 0.0001). CONCLUSION: Although
the number of days of leave of absence increased by 60%, there was no obvious
association with perinatal mortality for twins weighing < 1,500 g. The incidence
of Swedish twins with a birthweight < 1,500 g increased significantly, indicating
that the effect of leave of absence from work on perinatal outcome may be less
effective than previously thought.
PMID- 9645236
TI - Laurence-Moon-Bardet-Biedl syndrome. Clinical, electrophysiological and genetic
aspects.
PMID- 9645237
TI - Detection of Japanese encephalitis virus by reverse transcription/polymerase
chain reaction.
AB - A simple and rapid reverse transcription/polymerase chain reaction (RT-PCR) assay
for detection of Japanese encephalitis virus (JEV) envelope (E) gene sequences in
various biological samples is described. The assay successfully amplified JEV E
gene sequences from infected cell cultures, Aedes aegypti larvae, mosquitoes and
mouse blood. The sensitivity of the assay was currently 1 ng of JEV RNA and could
be increased up to 1 pg on the background of 1 microgram of cellular RNA by
biotinylation of the PCR product, Southern blot analysis and
streptavidin/alkaline phosphatase detection.
PMID- 9645238
TI - Genetic heterogeneity of Phthorimaea operculella granulovirus: restriction
analysis of wild-type isolates and clones obtained in vitro.
AB - Genetic heterogeneity of a wild-type granulovirus (Tunisia isolate) of the potato
tuber moth Phthorimaea operculella (Phthorimaea operculella granulovirus, Phop
GV) has been studied. The heterogeneity was indicated by the presence of several
submolar fragments in the profiles obtained by use of several restriction
endonucleases. It was also demonstrated by variations in the restriction profile
of the wild-type Tunisia isolate that had underwent since 1991 in our laboratory
numerous passages in vivo. A comparison of the Tunisia isolate used in Egypt in
the biological control programme with other PhopGV isolates indicated that it
could not be related to any of the 3 genotypes previously defined. Five clones
obtained from the Tunisia isolate in vitro were further grown both in vitro and
in vivo. The restriction analysis of these clones demonstrated that none of them
was identical to the parental wild type virus and to any other PhopGV geographic
isolates. Genotypic differences between the clones were also shown. A 19 kbp
BamHI fragment absent in the original Tunisia isolate but present in its passages
since 1995 at a submolar concentration, was always present at a molar
concentration in its clones. The presence of this fragment reflects probably a
selection of one or more variants present in the original isolate and its
possible adaptation to the growth in our laboratory conditions.
PMID- 9645239
TI - Prevalence of mutant CCR5 allele in Slovenian HIV-1-infected and non-infected
individuals.
AB - A 32 bp deletion in the CCR5 gene designated CCR5 delta 32 has been identified
recently as the cellular basis for resistance to human immunodeficiency virus
type 1 (HIV-1) in some individuals which remained non-infected despite a repeated
exposure to this virus. The prevalence of this deletion was examined by
polymerase chain reaction (PCR) on 51 HIV-1-infected and 385 non-infected
individuals from all parts of Slovenia. 84.4% of the the HIV-1-infected and 83.2%
of the non-infected individuals were homozygous for wild type CCR5, and 19.6% and
16.3%, respectively, were heterozygous. No homozygous mutant genotype was
observed among the HIV-1-infected patients. Of the non-infected individuals, 2
women (0.5%) were found to harbour the CCR5 delta 32/CCR5 delta 32 genotype only,
which is, to the best of our knowledge, the lowest prevalence of this particular
genotype found among Caucasians to date.
PMID- 9645240
TI - Genomic variations of hepatitis B virus strains in patients chronically
coinfected with hepatitis B and human immunodeficiency viruses.
AB - Serum samples from 56 human immunodeficiency virus type 1 (HIV-1)-infected adult
men were analysed for the presence of hepatitis B virus (HBV) serological
markers. Two or more samples from each patient, collected over an interval of 1-6
years, were tested. The antibody against HBV core antigen (anti-HBc) prevalence
was 79%. Three (5%) patients No. 5, 7, and 9 were chronic carriers of HBV surface
antigen (HBsAg). HBV DNAs from serial samples of these three patients and from
two HIV-seronegative control patients were characterised after amplification of
different genome regions by polymerase chain reaction (PCR). Size and restriction
analyses of the PCR products showed that samples from patients No. 7 (with
chronic active hepatitis) and 9 (asymptomatic) contained heterogeneous HBV DNA
populations. In patient No. 7, HBV DNA contained a precore gene stop codon
mutation at nucleotide (nt) 1896. In addition, a deletion in the core gene was
found in a sample collected two years after the onset of acquired
immunodeficiency syndrome (AIDS). PCR products from serial samples of patient No.
9 indicated a mixture of HBV DNA molecules that were cloned. Sequencing of the
pre-S region of the clones and phylogenetic analysis showed that patient No. 9
was superinfected with three HBV populations of distinct origin, all belonging to
genotype A. HBV DNA of patient No. 5 (with AIDS) did not present any variability
during a 6-year follow-up. Although two of three HIV/HBV coinfected patients
harboured heterogeneous HBV DNA populations during the follow-up, no common event
with respect to HBV DNA evolution was observed among the coinfected patients.
PMID- 9645241
TI - Electron microscopic examination of Aedes albopictus clone C6/36 cells infected
with dengue virus 2 at elevated incubation temperature.
AB - Morphological changes such as loss of cytoplasm, membrane destruction and
vacuolar swelling in Aedes albopictus clone C6/36 cells infected with dengue
virus 2 (DV-2) New Guinea B strain and incubated at 28 degrees C and 37 degrees
C, were observed under electron microscope. Both infected and uninfected cells
showed significant damage at 37 degrees C in contrast to normal appearance at 28
degrees C. A higher number of virus particles were observed in the cytoplasm at
37 degrees C than at 28 degrees C.
PMID- 9645242
TI - Syn strains HSZP and ANGpath [correction of ANG] of herpes simplex virus type 1
do not contain mutations in the regions of UL53 gene relevant to syncytium
formation.
AB - Parallel sequencing of UL53 gene of four strains of herpes simplex virus type 1
(HSV-1), two of which (HSZP and ANGpath) were of the syn phenotype while another
two (KOS and 17) were of the non-syn phenotype, showed in three strains amino
acid mutations unrelated to the already described syn1 glycoprotein K (gK)
mutations (Dolter et al., 1994). The only mutations which altered encoded amino
acids were found in strains HSZP (Gln to Arg at position 198) and ANGpath (Val to
Ile at position 137). Both mutations were localised outside of the two mutation
clusters suspected for affecting syncytium formation. In addition, a CG/GC
variation was found at positions 245-246 and 669-670. These compressions affected
three codons altering amino acids (aa) 82 (Cys or Ser), 223 (Me or Ile) and 224
(Leu or Val), respectively.
PMID- 9645243
TI - Interleukin-9 receptor alpha chain mRNA formation in CD8+ T cells producing anti
human immunodeficiency virus type 1 substance(s).
AB - A search for gene(s) associated with anti-human immunodeficiency virus type 1
(HIV-1) activity of CD8+ T cells was attempted using molecular cloning and the
relation between the anti-HIV activity of CD8+ T cells and the interleukin-9
receptor alpha chain (IL-9R-alpha) mRNA expression from the cDNA clones obtained
was examined. The anti-HIV-1 activity of CD8+ T cell culture supernatants was
assessed by measuring the level of HIV-1 replication of a CD4+ T cell line
transfected with an infectious HIV-1 DNA clone. IL-9R-alpha mRNA was assayed by
reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high
level of anti-HIV-1 activity (more than 80% suppression of HIV-1 replication),
the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-1
activity (less than 80% suppression of HIV-1 replication), the mRNA was detected
in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress
HIV-1 replication at a concentration of 1 microgram/ml. These data suggest that
the IL-9R-alpha mRNA formation in CD8+ T cells may correlate with and play some
role in the anti-HIV-1 activity of CD8+ T cells from HIV-1-infected individuals.
PMID- 9645244
TI - Characterisation of rearranged NSP5 gene of a human rotavirus.
AB - An atypical human rotavirus strain Z10262, isolated from a chronically infected
immunodeficient child, displayed an unusual genomic RNA electrophoretic pattern.
Besides, Northern blot analysis indicated that this strain contained an
abnormally migrating gene 11 equivalent. Sequencing of this gene showed that it
was derived from a genetic rearrangement which involved a partial duplication of
the open reading frame (ORF) encoding the non-structural protein NSP5. However,
the duplicated region contained a deletion and several point mutations relative
to the first copy of the ORF. Phylogenetic analysis of human and animal NSP5
amino acid sequences including Z10262 revealed two groups of human proteins
related to different animal proteins. The isolation and analysis of Z10262 strain
provides further evidence for the genetic complexity of naturally occurring human
rotaviruses.
PMID- 9645245
TI - Detection of Rickettsia sibirica in ticks and small mammals collected in three
different regions of China.
AB - The primers Rr 190.70p and Rr 190.602n were used to detect spotted fever group
(SFG) rickettsiae by polymerase chain reaction (PCR) in ticks and small mammals
collected in three different regions of China. The obtained results indicated
that specific DNA fragments of SFG rickettsiae were amplified from Dermacentor
silvarum, D. sinicus, D. auratus, Haemaphysalis concinna, H. wellingtoni, H.
yeni, Apodemus agrarius, Microtus fortis. Clethrionomys rufocanus, Ondatra
zibethica, Rattus flavipectus and hedgehog. The PCR product were digested with
restriction endonucleases PstI and RsaI and the obtained electrophoretic profiles
were compared with those of the prototype strains of SFG rickettsiae by the
restriction fragment length polymorphism (RFLP) technique. The comparisons showed
that the profiles were identical to those of Rickettsia sibirica. In addition,
three new isolates of R. sibirica were obtained from H. yeni, D. sinicus and
hedgehog, and designated NH-95, BJ-95 and BHJ-95, respectively. These results not
only demonstrated a horizontal transmission of the rickettsiae between ticks and
hosts but also suggested that R. sibirica is widely distributed in China and its
hosts and vectors are various, all that indicating the existence of natural foci
of North Asia tick-borne spotted fever specific to China.
PMID- 9645246
TI - [Liver tumors in children: spiral CT findings and differential diagnostic
classification].
AB - Liver tumors in childhood are rare. They can be subdivided in benign or primary
and secondary malignant liver tumors. The prognosis of malignant liver disease
has improved due to extended therapy in the past few years. Thus, diagnosis of
liver tumors in childhood gains in significance. After a suspect ultrasound
diagnosis, usually computed tomography (CT) is used as a radiologic sectioning
method. Guided by a retrospective analysis of 15 cases, the importance of the
Helical-CT is presented. Helical-CT is a good diagnostic method for pediatric
cases due to reduced scan times. By the basis of clinical data, distribution, and
density, various differential diagnoses can be made. Benign liver tumors,
especially cysts and frequently haemangioma, can easily be diagnosed and
controlled because of their typical echogenicity and contrast visualisation. In
cases of hamartoma, focal nodal hyperplasia, and adenoma computed tomography
diagnosis is often necessary. Primary malignant liver tumors can prove to be
unilocular hepatoblastomas or hepatocellular carcinomas, while disseminated liver
invasions usually are considered as metastatic liver tumors of kidney or adrenal
cancer.
PMID- 9645247
TI - [Cavitating lung lesions in the course of ANCA-associated vasculitis:
differential diagnostic aspects].
AB - Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's
granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite
variable courses. Clinical features of the full blown generalized systemic
vasculitis are usually found in the respiratory tract and the kidney. Pulmonary
involvement of Wegener's granulomatosis shows commonly nodules and cavitations
but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man
suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and
tinitus. Specimen of the kidney showed segmental glomerulosclerosis and
tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease
was assumed. Pulmonary infiltrates developed under immunosuppressive treatment
with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we
considered invasive pulmonary aspergillosis as well as infiltrates due to
Wegener's granulomatosis. In spite of maximal therapeutic management of patient
died of respiratory and cardiovascular failure. The findings at autopsy showed
distinct invasive pulmonary aspergillosis and perifocal hemorrhage.
PMID- 9645248
TI - [Imaging tumor extension of renal cell carcinomas with magnetic resonance
tomography. Improved tumor-tissue contrast with Gd-DTPA-assisted spin-echo
sequences and simultaneous fat suppression].
AB - PURPOSE: To evaluate the use of contrast-enhanced T1-weighted images with fat
suppression (T1FS) to improve the contrast-to-noise ratio of renal cancer and
renal parenchyma as well as perirenal fat. METHODS: 25 patients with
histologically proven unilateral renal cancer after nephrectomy were examined
before surgery. In addition to plane and contrast-enhanced T1-weighted as well as
T2-weighted spin-echo images, all patients had T1 FS immediately after
administration of Gd-DTPA in two planes. The contrast-to-noise ratio was
calculated using circular regions-of-interest which outlined the tumor, the renal
parenchyma, pyelon, and the perirenal fat. RESULTS: T1 FS significantly improved
the contrast-to-noise ratio of renal cancer and renal parenchyma compared to all
conventional spinecho sequences (p < 0.001; Wilcoxon-Test). Compared to contrast
enhanced T1-weighted images without fat-suppression T1 FS yielded a higher CNR of
the tumor, the perirenal fat and the pyelon. Another advantage was the absence of
the chemical-shift artifact which is mostly pronounced in T2-weighted images and
a reduced number of observed artifacts due to breathing. CONCLUSION: T1 FS should
replace conventional contrast-enhanced T1-weighted spin-echo images in the work
up of renal cancer using MRI.
PMID- 9645249
TI - [Calculating the effective dose of occupationally exposed persons in roentgen
diagnosis].
AB - The radiation exposure of occupationally exposed staff was measured at tube
voltages of 50, 80 and 100 kV. A typical arrangement for fluoroscopic
examinations was chosen: the (standing) physician is exposed by the scattered
radiation from a (lying) patient. The physician is represented by an Alderson
Rando-Phantom and a spherical phantom similar to an ICRU sphere. Measurements of
the partial body dose were performed by film dosimetry in the Alderson-Rando
Phantom in a.p. and in lateral direction of the scattered radiation respectively.
From these measurements the effective dose was calculated. The ambient equivalent
dose H* (10) in the sphere phantom was determined by the same method. The latter
results yield the conversion factor g, which describes the ratio effective dose E
to ambient equivalent dose H* (10). A conversion factor of g = 0.3 was
established by averaging over the tube voltage and the direction of the scattered
radiation. Based on the guidelines 96/29/Euratom and the transition from old to
new dose quantities a reduction of the dose limits for occupationally exposed
persons by a factor of up to 3.75 will be necessary. Applying the conversion
factors can almost compensate that reduction.
PMID- 9645250
TI - [Heavy metal incorporation as an unusual self-injury].
AB - A 19-year-old man was admitted to hospital because of uncharacteristic neurologic
symptoms. During the first examination morphologic alterations due to an
injection of mercury into the left arm and the left side of the trunk were found.
The dose and the manner of application were doubtful and suspected to be a case
of self-infliction. The man informed the police only 7 months later because his
relatives had finally persuaded him to do so. The description of the infliction
by unknown perpetrators was full of contradictions. Initially the patient gave
only an indistinct description. But later on, the number of details increased. At
the same time there was a change in the characteristics of the perpetrator(s).
Other differences existed concerning a loss of consciousness which should have
been caused by a single stroke on an arm. Furthermore, the patient told about a
swelling as big as an egg, provoked by an injection of liquid mercury. It could
be shown by experiments that mercury can be injected into soft-tissue very simply
and that it spreaded widely. Arguments for a self-injection were e.g. the
technical possibility, the topography of the injection marks, and an easy
handling of the syringe. A psychiatric examination furthermore revealed, that the
patient had had periods of restriction of thinking, sometimes combined with a
lack of appreciation.
PMID- 9645251
TI - [Symptomatic heterotopic splenic tissue in the adrenal gland area].
AB - We report on a 33-year-old man with symptomatic heterotopic suprarenal splenic
tissue. Heterotopic splenic tissue can often be found after posttraumatic
splenectomy. It is a result of autotransplantation induced by trauma (splenosis).
Additionally it can grow during embryogenic development. Such an accessory spleen
is found in 10-44% of all autopsies. In this case report the patient was treated
by resection due to increasing flank pain and suspected neoplasm.
PMID- 9645252
TI - [Emphysematous pyelonephritis].
AB - Emphysematous pyelonephritisis a relatively rare, gas-producing, destructive and
usually unilateral renal infection. Often the patients are female diabetics and
mostly the left kidney is affected. The pathological gas formation is either
limited to the kidney or extends to the perirenal space. Two cases are reported,
which-in clinical presentation, extension of pathological gas, and treatment
present two possible ends of the spectrum of this disease.
PMID- 9645253
TI - [Endosteal hyperostosis--differential diagnosis and possible therapeutic
outlook].
AB - A case report on a 42-year old man with an osteosclerotic bone disorder is
presented. Physical examination and radiological findings are in favour of
endosteal hyperostosis. Differential diagnoses are discussed.
PMID- 9645254
TI - [Primary non-Hodgkin lymphoma of the ovary].
AB - A young female patient was admitted for clarification of a space-occupying
ovarian situation. Histological analysis gave the finding of a highly malignant
NHL of the Burkitt type. In the further course of the disease bicytopenia
developed. Bone mark analysis revealed a B-AII. FAB L3 which can be considered as
the leukemic equivalent of the Burkitt lymphoma. In spite of chemotherapy the
patient died as a consequence of a sepsis.
PMID- 9645255
TI - [Right-sided double inferior vena cava and common iliac vein: imaging with spiral
computerized tomography].
AB - Duplications of the inferior vena cava (IVC) are rare variants of the abdominal
vessels and are normally located on both sides of the abdominal aorta. The rare
case of a rightsided infrarenal duplication of the IVC with involvement of the
common iliac vein is reported. Details of the embryology are presented for the
understanding of this IVC variant. The spiral CT with multiplanar reconstructions
makes it possible to define the vascular morphology and to differentiate it from
lymphoma.
PMID- 9645256
TI - [Comparison of film-screen combinations in contrast-detail diagram and with
interactive image analysis. 3: Trimodal histograms of gray scale distribution in
bar groups of lead pattern images].
AB - The following four screen film combinations were compared: a) a combination of
anticrossover film and UV-light emitting screens, b) a combination of blue-light
emitting screens and film and c) two conventional green fluorescing screen film
combinations. Radiographs of a specially designed plexiglass phantom (0.2 x 0.2 x
0.12 m3) with bar patterns of lead and plaster and of air, respectively were
obtained using the following parameters: 12 pulse generator, 0.6 mm focus size,
4.7 mm aluminum prefilter, a grid with 40 lines/cm (12:1) and a focus-detector
distance of 1.15 m. Image analysis was performed using an Ibas system and a Zeiss
Kontron computer. Display conditions were the following: display distance 0.12 m,
a vario film objective 35/70 (Zeiss), a video camera tube with a PbO
photocathode, 625 lines (Siemens Heimann), an Ibas image matrix of 512 x 512
pixels with a spatial resolution of ca. 7 cycles/mm, the projected matrix area
was 5000 micron 2. Maxima in the histograms of a grouped bar pattern were
estimated as mean values from the bar and gap regions ("mean value method"). They
were used to calculate signal contrast, standard deviations of the means and
scatter fraction. Comparing the histograms with respect to spatial resolution and
kV setting a clear advantage of the UVR system becomes obvious. The quantitative
analysis yielded a maximum spatial resolution of approx. 3 cycles/mm for the UVR
system at 60 kV which decreased to half of this value at 117 kV caused by the
increasing influence of scattered radiation. A ranking of screen-film systems
with respect to image quality and dose requirement is presented. For its
evaluation an interactive image analysis using the mean value method was found to
be superior to signal/noise ratio measurements and visual analysis in respect to
diagnostic relevance and saving of time.
PMID- 9645257
TI - [Roentgen diagnosis without medical indications and physical injury. Verdict of
the federal court 3 December 1997--2 StR 397/97].
AB - An orthopedist had been sentenced for different offenses to two years and six
months imprisonment by the Landgericht Frankfurt (superior court). One point of
the ruling had been the evaluation of the use of X-ray methods without medical
indication, which the Landgericht Frankfurt/Main (superior court) finally did not
evaluate as bodily harm. The Bundesgerichtshof (supreme court) of Germany
overruled this interpretation and referred the case back for new trial and
ruling.
PMID- 9645258
TI - Usefulness and limitations of PEF.
PMID- 9645259
TI - A study of allergy to penicillin antibiotics in 1995 in the Child Allergy
Department of the Gregorio Maranon University hospital.
AB - We present 219 cases of adverse reactions to penicillin and related antibiotics
during 1995 in the Child Allergy Department of Gregorio Maranon University
Hospital. Amoxicillin was the most frequent cause of the reaction. The most
common clinical symptom was urticaria followed by angio-edema and other
characteristic exanthemas. A diagnosis of allergy to penicillin and related drugs
was only made in 20 cases in which the predominant symptomatology was urticaria
and the antibiotic most commonly involved was again amoxicillin. Diagnosis was
confirmed by a skin test, specific IgE determination and controlled provocation.
In 3 of the 20 cases diagnosis was made in the reassessment or second study,
which was carried out in all cases in which more than one year had passed between
the reaction and the initial allergological study.
PMID- 9645260
TI - Assessment of the inhalation technique in asthmatic patients: a comparative study
of three aerosol devices.
AB - Local administration of drugs by means of aerosol device is widely used in the
treatment of asthma. Nevertheless, the effectiveness of this method depends on an
adequate inhalation technique (IT), which available evidence has shown to be
rather problematic. The aim of this study was to assess IT in out-patients with
bronchial asthma who frequently use aerosol therapy with Pressurized Metered dose
inhalers (MDI), pressurized inhalers with spacer (MDI-S) and the Astra-Draco
Turbuhaler system (TH). A sample of 150 adults with asthma were evaluated. These
patients had been followed up for than two years and they often used one of the
devices mentioned above. The IT has broken down into several steps for each
procedure. Percentages of patients with one error in the IT were 50%, 44% and 42%
for MDI, MDI-S and TH procedures, respectively. 18%, 20% and 14% of patients
committed three errors in the IT, respectively. Differences detected were not
significant. Seven patients committed errors in every step of the IT. In
conclusion, the level of errors found in our study is high, similar to that cited
in the existing literature. It is also roughly equivalent for the three devices
tested. We believe that the proper teaching monitoring of IT skills is highly
important in the treatment of bronchial asthma.
PMID- 9645261
TI - Serum immunoglobulin E levels in relation to adenoid surgery.
AB - The adenoid tissue is an immunecompetent lymphoid organ, which has the capacity
of reacting against numerous antigens. We have studied the influence that the
elimination of the said tissue would have on the total IgE serum levels in 33
patients of an average age of 5 and criteria of adenoidectomy and in whom these
levels were measured before and after surgery. We have not noticed any
statistically significant differences in the IgE values after adenoidectomy with
respect to those prior to surgery, which were normal. Adenoidectomy, like other
authors have observed after tonsillectomy, does not alter the IgE serum values.
PMID- 9645262
TI - Stevens-Johnson syndrome from tetrazepam.
AB - We present a case of a patient showing a cutaneous and systemic affectation
compatible with the Stevens-Johnson syndrome due to the intake of tetrazepam as a
muscular relaxant. The symptoms remitted after the suspension of the involved
medicines and after treatment with systemic corticoids. Months later, a study
with patch tests, with the standard battery and the medicines that she took
(indapamide, tetrazepam, acetyl salicylic acid, botriozolam and levomepromazine)
was carried out. She presented positivity to tetrazepam at 48 and 96 hours. The
oral provocations with the other medicines, which she consumed, were negative.
The study of cross reactivity with other benzodiazepines was negative. In the
medical literature, different cutaneous affectations regarding benzodiazepine use
(generalised drug eruptions, contact dermatitis, erythema multiforme, ...) have
been described byt non Stevens-Johnson syndrome. The patch tests are useful in
the diagnosis of this type of cutaneous reactions, avoiding in this way the
achievement of oral provocations, with the potential risk for the patient that
they imply. The absence of cross-reactions with other substances of the same
group has to be pointed out, even with those with which keeps great structural
similarity as the diazepam. In spite of the absence of cross reactions with the
rest of benzodiazepines, faced with the seriousness of the case presented, it is
advised to the patient to avoid this type of medicines.
PMID- 9645263
TI - [Biological and genetic basis of atopy and asthma].
AB - Atopy is triggered by allergens and enhanced by environmental factors, but it has
a clear genetic basis, as it is confirmed by the high incidence in siblings and
twins. In the last few years, many authors have published genetic studies on
asthmatic and atopic patients, generally with very controversial results. In the
present article, IgE regulation and other immunological mechanisms which are
assumed to be involved in the atopic reaction are reviewed. In the second part,
the coding genes of factors, cytokines and receptors that take part in the atopy
are commented, as well as review of the recent articles published about genetic
markers or polymorphisms associated to these genes. The unveilling of the genetic
background of atopy and asthma is a very difficult task, and it will need the
definition of a specific atopic phenotype and a clear knowledge of the
immunologic basis of atopy. Finally, due to racial and geographical variations a
wide collaborative study of many research groups distributed all over the world
will be needed.
PMID- 9645264
TI - Early recognition of pregnancy by the maternal immune system.
AB - PROBLEM: Immunologic recognition of pregnancy is important for normal gestation.
Successful pregnancy is characterized by a Th2 dominance, whereas there is a Th1
dominance in failed pregnancies. We assume that a signal given by the fertilized
ovum induces a Th2 shift, necessary for a normal outcome. In vitro fertilization
provides a tool for testing this possibility. METHOD OF STUDY: Phytohemagglutinin
stimulated lymphocytes were incubated for 48 hr in the presence of culture media
from in vitro fertilized eggs, as well as in follicular fluid (FF) and control
supernatants. Total RNA was isolated from the lymphocytes by the guanidine
isothiocyanate method and interleukin (IL)-10 mRNA expression was detected by
reverse transcription-polymerase chain reaction. RESULTS: Ten percent of the
activated lymphocytes incubated with FF expressed IL-10 mRNA, whereas 88% of the
lymphocytes activated with supernatants of sperm + oocytes gave a positive
signal. Significantly (P < 0.05) fewer (50%) lymphocytes stimulated in the
presence of control supernatants also expressed mRNA for IL-10. In supernatants
of activated lymphocytes incubated with the culture medium of spermia + oocytes,
the concentration of IL-10 was significantly higher than in the lymphocytes
incubated with FF. CONCLUSION: These data suggest that the presence of the
fertilized ovum induces a Th2 shift, which enables pregnancy to proceed to term.
PMID- 9645265
TI - Supplementation effect of early pregnancy factor-positive serum into bovine in
vitro fertilization culture medium.
AB - PROBLEM: Early pregnancy factor (EPF) has been detected in pregnant bovine serum,
and its activity appeared from 24 to 48 hr after insemination. However, in bovine
in vitro fertilization (IVF), an EPF-like substance(s) had been detected in the
culture medium of fertilized ovum. Therefore, we think that EPF and EPF-like
substance(s) are very important materials for the development of the embryo. In
this study, we examined the development of the embryo when fertilized bovine ova
were cultured with IVF culture medium supplemented with EPF-positive or -negative
serum. METHOD OF STUDY: EPF activity of each serum (fetal calf serum [FCS], calf
serum [CS], estrus bovine serum, and pregnant bovine serum) was assessed by the
bovine-rosette inhibition test. The sera were supplemented in TCM-199 culture
medium, and IVF bovine ova were cultured with the media for 6 or 7 days,
respectively. The culture media of each group were evaluated for EPF activity by
the bovine-rosette inhibition test 48 hr after IVF. The cleavage rate of each
group was calculated at 48 hr, and 6 or 7 days after IVF. The culture medium of
cumulus cells was also tested for EPF activity. RESULTS: Only the pregnant bovine
sera were EPF positive. All the culture media 48 hr after IVF became EPF
positive. Additionally, the culture medium of cumulus cells did not have EPF
activity. There was no significant difference in the cleavage rate of the EPF
positive and -negative sera 48 hr after IVF. However, the cleavage rate of EPF
positive sera tended to be higher than the negative sera. In contrast, the
blastocyst development rates of EPF-positive sera were significantly higher than
those of the negative sera 6 to 7 days after IVF (P < 0.05). CONCLUSIONS: The
data suggest that an EPF-like substance(s) may be secreted from the in vitro
fertilized bovine ovum but not from the cumulus cell, and that the EPF in the
pregnant serum may accelerate the development of the bovine embryo in IVF.
PMID- 9645266
TI - Increased numbers of circulating interferon-gamma- and interleukin-4-secreting
cells during normal pregnancy.
AB - PROBLEM: Systemic immune responses during normal pregnancy are suggested to
deviate toward secretion of T helper (Th)2-like cytokines. METHOD OF STUDY: Blood
samples from 11 healthy primigravidae in their first, second, and third
trimesters, and 8 weeks postpartum were examined. Peripheral blood mononuclear
cells were separated and the numbers of interferon (IFN)-gamma- and interleukin
(IL)-4-secreting cells were identified by using the enzyme-linked immunospot
test. RESULTS: In all three trimesters of pregnancy, and also postpartum, the
numbers of IFN-gamma- and IL-4-secreting cells were significantly higher compared
with nonpregnant controls (Mann-Whitney; P < 0.001). The numbers of IFN-gamma-
and IL-4-secreting cells gradually increased as the pregnancy progressed compared
with postpartum (Kruskas-Wallis; P < 0.01 and P < 0.05, for IFN-gamma and IL-4,
respectively). The ratios of IFN-gamma/IL-4 during pregnancy and postpartum were
unchanged, and also when compared with nonpregnant controls. CONCLUSION: The
results indicate a systemic up-regulation of both Th1- and Th2-like immune
responses during normal pregnancy.
PMID- 9645267
TI - Identification of a unique form of p53 in human cord blood associated with the
development of maternal autoantibodies.
AB - PROBLEM: The possible link between p53-reactive antibodies in multiparous women
and exposure to a unique p53 protein during pregnancy was examined. METHOD OF
STUDY: p53-reactive antibodies were evaluated in sera from nulligravid and
multiparous women and patients with ovarian cancer by Western immunoblot.
Furthermore, the presence of p53 protein was assayed in cord blood by enzyme
linked immunosorbent assay. Cord blood-derived p53 was compared structurally by
protein fingerprinting and functionally by gel mobility shift assay to other
isolates of p53. RESULTS: Antibodies reactive with wild-type p53 were observed in
92% of multiparous women and 42% were reactive with one tumor-derived p53
protein. p53 protein was detected in 27 of 154 samples of cord blood. Structural
analysis indicated that the fetal p53 resembled the UL-1 p53. Functionally, the
fetal and UL-1 protein failed to bind DNA. CONCLUSIONS: Fetal p53 protein seems
to be distinct from wild-type p53, characterized by enhanced stability,
structural differences and inability to bind DNA, analogous to alternatively
spliced variants. Exposure to fetal p53 protein may form the basis for
immunologic protection against cancer induced by multiparity.
PMID- 9645268
TI - Plasma interleukin-12 is elevated in patients with preeclampsia.
AB - PROBLEM: Abnormal immune activation has been suggested as a contributor to the
development of preeclampsia. We hypothesized that intact interleukin (IL)-12
directly, or through its main mediator, interferon (IFN)-gamma, contributes to
the altered immune response observed in preeclampsia. METHOD OF STUDY: Plasma
samples were collected from 20 patients with preeclampsia and 20 normotensive
patients with uncomplicated pregnancies who were matched with the preeclamptic
patients by age, gestational age, and parity. Samples were collected before the
onset of labor, induction, or medical intervention. The samples were assayed for
IL-12 and IFN-gamma by specific enzyme-linked immunoassays. RESULTS: IL-12 was
detected in 35% of the preeclamptic patients and in 5% of the patients with
normal pregnancies (P < 0.01). The detection rate and mean concentration of IFN
gamma were comparable in both groups. CONCLUSION: Intact plasma IL-12 is detected
more frequently in preeclamptic patients, suggesting the involvement of this
cytokine in the enhanced immune response observed in preeclampsia.
PMID- 9645269
TI - Neutralizing antibodies and complement-mediated, antibody-dependent enhancement
(C'-ADE) of human immunodeficiency virus infection in its vertical transmission.
AB - PROBLEM: Mother-to-child transmission is a major route for the spread of human
immunodeficiency virus (HIV) worldwide. Our understanding of its mechanisms and
parameters is still limited. Among the factors possibly involved in virus passage
determination are the level and quality of antiviral humoral response. METHOD OF
STUDY: Anti-HIV-1/Lai neutralizing activity in sera from 35 mother-infant pairs
(in which 13 transmission cases occurred) was investigated, as was the complement
mediated antibody-dependent enhancement capacity of the same sera. RESULTS:
Neutralization titers of 640 or more were found only in four mothers of
uninfected children, but this result was not significant. No significant link was
obtained with the occurrence of complement-mediated, antibody-dependent
enhancement. CONCLUSIONS: As suggested by a synthesis of the literature, vertical
transmission of HIV is probably the result of multiple active and/or stochastic
parameters in the mother, the fetal structures, and the viral population. The
precise definition of cellular mechanisms involved in in utero infection would
help to better define which immune activity in the mother should be more
carefully considered.
PMID- 9645270
TI - Gonadotropins induce the release of interleukin-1 beta, interleukin-6 and tumor
necrosis factor-alpha from the human preovulatory follicle.
AB - PROBLEM: The effects of exogenous gonadotropin administration and steroid levels
on the release of various cytokines into the human follicular fluid (FF) were
studied. METHOD OF STUDY: Forty patients were included in two groups, those
undergoing controlled ovarian hyperstimulation (COH) (n = 33) and natural cycles
(n = 7). FF transvaginal aspirations were performed 36 hr after administration of
human chorionic gonadotropin or a spontaneous surge of luteinizing hormone,
respectively. FF cytokine measurements were performed with sensitive
immunoassays. RESULTS: FF cytokine levels were higher after COH [interleukin (IL)
1 beta, 6.6 +/- 0.32 pg/ml; IL-6, 18.7 +/- 2.1 pg/ml; and tumor necrosis factor
(TNF)-alpha, 32.5 +/- 4.9 pg/ml] than in natural unstimulated cycles (0.52 +/-
0.1 pg/ml, P < 0.001; 8.9 +/- 1.2 pg/ml, P < 0.01; and 13.2 +/- 2.6 pg/ml, P <
0.001, respectively). FF estradiol (E2) and progesterone levels were not
statistically different between groups, despite the higher serum E2 levels
observed in patients after COH. CONCLUSIONS: Gonadotropins might regulate ovarian
secretion of cytokines, because FF IL-1 beta, IL-6, and TNF-alpha levels after
COH were higher than during natural cycles.
PMID- 9645271
TI - A rational basis for the use of combined heparin/aspirin and IVIG immunotherapy
in the treatment of recurrent IVF failure associated with antiphospholipid
antibodies.
AB - PROBLEMS: 1) Does the administration of heparin and aspirin (H/A) in combination
with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF)
implantation and birth rates in patients with recurrent IVF failure? 2) Is the
effect of such treatment related to the antiphospholipid antibody (APA) status of
the patients concerned? METHOD OF STUDY: Subjects consisted of 89 women younger
than 36 years of age whose infertility was a result of causes other than male
infertility and who had experienced four or more failed IVF/embryo transfer
procedures. Fifty-two women were APA+ (group A), and 37 were APA- (group B). All
patients, regardless of their APA status, received H/A (5000 U sq bid), aspirin
(81 mg po qd) from the inception of menotropin therapy along with IVIG (20 g)
through a single infusion 3 to 10 days before egg retrieval. RESULTS: Twenty-two
(42%) of group A and 7 (19%) of group B patients achieved live births (P =
0.020). CONCLUSIONS: IVF outcome is significantly improved when H/A and IVIG are
administered to APA+ women with repeat IVF failures. APA- women do not seem to
benefit from such treatment.
PMID- 9645272
TI - Regain of fertility and normality of progeny born during below protective
threshold antibody titers in women immunized with the HSD-hCG vaccine.
AB - PROBLEM: Phase II clinical trials with the heterospecies dimer of beta hCG and
alpha-subunit of ovine luteinizing hormone (HSD)-human chorionic gonadotrophin
(hCG) vaccine showed that pregnancy was prevented at and above 50 ng/ml titers,
whereas conceptions occurred below 35 ng/ml of hCG bioneutralization capacity.
The effect of below-protective threshold anti-hCG antibodies on the progression
of pregnancy and the normality of progeny was studied. METHOD OF STUDY: Four
women enrolled by informed consent in the Phase II trials. The women studied were
immunized with the HCG vaccine and did not receive booster injections in
consideration of their desire to have another child. They were examined
clinically at least once every month until delivery. The babies were followed up
from 2 to 3.5 years, and their anthropometric indices were compared with elder
siblings. RESULTS: The pregnancies progressed to 35 to 38 weeks with the usual
obstetric problems, and the children developed normally. CONCLUSIONS: The anti
fertility effect of the HSD-hCG vaccine is reversible and low titers of
antibodies below the protective threshold have no apparent side effects on the
progression of pregnancy and on the early development of the progeny.
PMID- 9645274
TI - [Problems and tendencies in monitoring].
PMID- 9645273
TI - Immunodetection of cell adhesion molecules in rat Sertoli cell cultures.
AB - PROBLEM: The presence of cell adhesion molecules (CAMs) in Sertoli cells has not
been explored extensively. The expression of CAMs involved in cell-matrix and
cell-to-cell interactions in Sertoli cell cultures was examined. METHOD OF STUDY:
Immunohistochemical and Western blot techniques were applied to rat Sertoli cell
cultures using specific antibodies to alpha 3, alpha 5, and alpha 6 integrin
subunits; NCAM; and cadherins. RESULTS: Expression of alpha 3 and alpha 6
integrin subunits (mainly laminin receptors) and lack of expression of alpha 5
integrin subunit (fibronectin receptor) was observed in Sertoli cells by
immunohistochemistry. These cells also expressed neural CAM (NCAM) and N
cadherin. By Western blot analysis, Sertoli cell extracts reacted with antibodies
to alpha 3 integrin subunit revealed a band approximately 130 kDa, whereas no
expression of alpha 5 integrin subunit was detected. Cell extracts incubated with
antibodies to pan cadherin exhibited a band approximately 120 kDa, whereas bands
of 180, 140, and 120 kDa were observed with antibodies to NCAM. CONCLUSION: New
data about the expression of receptors for extracellular matrix proteins (alpha 3
and alpha 6 integrin subunits) as well as cell-to-cell adhesion molecules (NCAM
and cadherins) are reported in rat Sertoli cell cultures.
PMID- 9645275
TI - [Monitoring in anesthesiologic practice].
AB - Monitoring has made great strides in the last half century. It enables us to
titrate drugs to the desired effect, warns us of impending danger, and helps with
the diagnosis of problems confronting our patients. Beyond that it has enormously
increased our understanding of anesthetic pathophysiology. Modern monitors,
however, are still focused on single variables; they do not provide the panoramic
view offered by our senses. They do not give data on the patient's appearance,
movement, or position. The clinician incorporates that type of information with
the data provided by the monitors and melds that with a much richer information
about the system in which the operates, the colleagues with whom he works and the
circumstances that affect his patient. Even though we appreciate the importance
of that wealth of information, we lack scientific tools to measure its value.
PMID- 9645276
TI - [Preoperative ECG in routine preoperative assessment of children].
AB - OBJECTIVE: The aim of this study is to examine whether a routine preoperative ECG
is necessary in children to assess the risks in anaesthesia and surgery. METHODS:
We examined the records of 3030 children anaesthetized in our hospital in 1990
and compared records of complications with preoperative ECGs. We also evaluated
questionnaires on this subject which we had sent to 51 large pediatric hospitals
in Germany in 1991. RESULTS: During 3030 anaesthetic procedures there were 93
complications, 67 of which were not of cardiac origin. Of the 26 cardiac
complications only 4 needed therapy (AV-Block 2 degrees, fall in blood pressure).
Preoperative ECGs were recorded in 180 cases: 152 were normal, 8 showed harmless
deviations from normal and 16 were recorded because of known cardiac defects.
None of the 180 children developed complications during anaesthesia. Our
questionnaire was returned completed carefully by 36 of the 51 hospitals. In most
hospitals a preoperative ECG is only recorded when heart disease is known or
suspected. CONCLUSION: Routine preoperative ECGs are unnecessary in children
unless there are clinical symptoms of heart diseases or heart disease is
suspected.
PMID- 9645277
TI - [Cytokine release and changes in mononuclear cells in peripheral blood under the
influence of general anesthesia].
AB - OBJECTIVE: Anaesthetic agents are believed to have an adverse effect on human
immune defense mechanisms. We investigated changes in peripheral immune cell
numbers such as natural killer (NK) cells, B cells and T lymphocyte
subpopulations (CD4+ and CD8+ cells) and differences in cytokine production after
stimulation with different mitogens before and during narcosis. METHODS: We
studied 30 patients undergoing elective orthopedic surgery. Stimulatory
experiments were performed with the mitogens lipopolysaccharide (LPS),
phytohemagglutinin (PHA) and inactivated Newcastle Disease Virus (NDV). RESULTS:
During general anaesthesia with fentanyl, thiopental, isoflurane and nitrous
oxide there was a significant decrease of circulating NK cells in the peripheral
blood accompanied by a significant increase of B cells and CD8+ T lymphocytes. We
detected a significant anesthesia-associated increase of interferon (IFN)-gamma,
INF-alpha, tumor necrosis factor (TNF)-alpha and soluble interleukin-2 receptor
(sIL-2R) synthesis after stimulation with different mitogens while interleukin
(IL)-1 beta and IL-6 protein did not change significantly. After the beginning of
surgery CD8-positive cells showed a return to control values and NK cell number
increased slightly. CONCLUSION: These findings suggest that general anaesthesia
interferes with immune cell number and immune cell response. This may explain the
clinically well-recognized disturbance of human immunity after surgery and
general anaesthesia.
PMID- 9645278
TI - [Are tramadol enantiomers for postoperative pain therapy better suited than the
racemate? A randomized, placebo- and morphine-controlled double blind study].
AB - The goal of this prospective, randomised and double-blind pilot-study was to
investigate the analgesic potency and the side-effects of tramadol enantiomers in
clinical practice. One hundred patients recovering from orthopaedic surgery with
a postoperative pain intensity of more than 50 on a visual analogue scale 0-100
mm (Table 1) were recruited for the study. They were treated in a randomised,
double-blind way with a maximal dose of 150 mg i.v.(+)-,(-)-tramadol, racemate,
or 15 mg i.v. morphine or saline in the placebo group (5 groups, 20 patients
each). The primary criterium of efficacy was the number of responders defined as
patients with a pain reduction of at least 20 on VAS after 40 min. In case of
pain, responders were allowed to continue with the double-blind drug up to six
hours. The non-responders were treated with morphine as the rescue analgesic. The
secondary criterium was the incidence and severity of side-effects. Six patients
terminated the study prematurely. One patient was excluded because of an allergic
reaction to morphine, one patient could not be treated sufficiently with
morphine, four were excluded because of protocol violations. There were 8
responders in the (+)-tramadol-,6 in the (-)-tramadol- and 6 in the racemate
group, 16* (P < 0.05) in the morphine group, and 5 in the placebo group. Pain
intensity after 40 min was reduced by 20 (p < 0.05), 17 (p < 0.05), 17 (p <
0.05), 36 (p < 0.01 vs placebo, p < 0.05 vs (+)-,(-)-tramadol, and racemate
group) and 5 mm on the VAS in the (+)-, (-)-, (+/-)-tramadol-, morphine- and
placebo-group, respectively. Thirty eight adverse events like nausea, vomiting,
PCO2-increase, and urinary retention occurred in 20 patients, most frequently in
the (+)-tramadol- and morphine group. Sedation was significantly less profound in
the (-)-tramadol group 1-4 h postoperatively. There were no side-effect in the
tramadol racemate group. The enantiomers were equal to the racemate in analgesic
potency, but inferior by far to morphine. They showed more adverse events and,
hence, can not be preferred to the racemate in postoperative pain therapy.
PMID- 9645279
TI - [Is there a means for cost reduction in intensive care fluid therapy without a
loss of quality?].
AB - Cost reduction in fluid therapy may be possible without a loss in quality of
medical therapy if the following principles are adhered to. 1: Compare the prices
of different manufacturers. 2: The greater the product unit, the cheaper the
milliliter. Adherence to this principle is limited by hygienic and logistic
considerations. 3: 0.9% NaCl-solution is cheaper than Ringer's lactate-solution.
Lactated Ringer's solution should be used, only, if there are contraindications
against the higher solute concentrations and tonicity of 0.9% NaCl. 4:
Crystalloids are cheaper than colloids. When choosing between these two options
intravasal duration of action and specific adverse events must be considered. 5:
Cost reduction by differential indication of artificial colloids. Comparing
prices, one must consider risk of anaphylactoid/anaphylactic reactions, duration
of action, limitation of dosage and possible hemostasis disorders. 6: Restrictive
use of albumin. Albumin is the most expensive colloid. There are no reasons for
routine use.
PMID- 9645280
TI - [Preclinical blood gas analysis. 1. The value of preclinical blood gas analysis].
AB - Prehospital blood gas analysis is a new method in out-of-hospital emergency care.
In a prospective pilot study we evaluated the feasibility of prehospital
compensation of severe acidosis relying on different monitoring systems to
evaluate patients oxygen, carbon dioxide or acid-base status, respectively.
METHODS: With the help of arterial blood gas checks taken at the site of the
emergency, the acid base status of patients undergoing out of hospital
cardiopulmonary resuscitation was analysed. The values derived from the first
arterial puncture were used to determine the presence and the type of acidosis.
The data of the arterial blood gas checks were set into relation with the time
elapsed since the beginning of resuscitation and they were compared with end
tidal CO2. RESULTS: During the observation period 26 blood gas analyses from
patients who had out-of-hospital resuscitation because of cardiac arrest were
done. Twenty three patients had severe acidosis (pH range < 6.9 to 7.31), one had
alkalosis (pH 7.51). Only two had an arterial pH within normal range. The pCO2
was variable (range: 24 to 97 mm Hg). The correlation of pH with time from the
beginning of resuscitation to arterial puncture was poor (r = 0.407, p < 0.05).
There was no correlation between pH and BE (r = 0.267) or pH and pCO2, (r =
0.016) respectively. Prehospital capnometry had a poor correlation with arterial
pCO2 in most emergency patients. Only patients with respiratory disturbances of
extrapulmonary origin showed a good correlation between end-tidal CO2 and the
arterial pCO2. In severely ill patients the arterio-alveolar CO2-difference was
unexpectedly high (> 15 mm Hg). In four patients resuscitation was not successful
until compensation of an unexpectedly severe acidosis based upon the findings
from blood-gas analysis had been performed. CONCLUSIONS: Arterial blood gas
analysis proved to be helpful in the optimal management of out of hospital
cardiac arrest. The incidence of severe acidosis in patients undergoing
cardiopulmonary resuscitation was 80%. The probability of developing acidosis was
found to increase slightly depending on the time elapsed since the beginning of
CPR. The application of a calculated buffering of acidosis with sodium
bicarbonate showed a good outcome in selected cases. In emergency patients
alternative methods fail to detect severe disturbances of the patients oxygen
and/or carbon dioxide status and the acid-base balance. Management of prehospital
cardiac arrest could be optimized by the routine use of blood gas analysis.
PMID- 9645281
TI - Validating of a transoesophageal ultrasonic-Doppler-probe to the detection of air
in the venous blood.
AB - OBJECTIVES: The aim of this study was to compare the sensitivity of a newly
applied transoesophageal ultrasonic Doppler sensor for detection of air with the
traditional precordial ultrasonic Doppler sensor in clinical use. METHODS: We
studied 16 patients undergoing neurosurgical procedures in a sitting position.
Two ultrasonic Doppler devices were compared as to their ability to detect venous
air embolisms (VAE): transoesophageal (ODM II, co. Abbott) versus a precordial
ultrasonic Doppler sensor (Parks Medical Electronics Inc.). After establishing
general anaesthesia and endotracheal intubation, we applied an ultrasonic Doppler
sensor to the right sternal border of the patient's chest and inserted an
ultrasonic Doppler probe into the oesophagus. With the patient in the sitting
position, microparticularly d-galactose was injected to verify the efficacy of
both ultrasonic Doppler devices. RESULTS: Using ODM II by positioning the probe
toward the azygos vein, a dosage of 1 ml microparticularly d-galactose was
detected in every patient. When adjusting the ODM II-probe on the right
myocardial wall or using the precordial ultrasonic Doppler sensor, the
administration of microparticularly d-galactose was detected by the devices in
only 11 patients. CONCLUSIONS: This study demonstrates that a transoesophageal
ultrasonic Doppler sensor (ODM II) is more efficient than the precordial
ultrasonic Doppler sensor for monitoring patients who are at risk of VAE by
sonification of the azygos vein.
PMID- 9645282
TI - [New results in the visualization of the spinal dura mater with scanning electron
microscopy].
AB - Although there are various published descriptions of the dura mater spinalis [4,
7, 9, 11, 16], some points relating to the texture of the collagen fibres in the
dura have still not been adequately explained. In this study the orientation of
the collagen fibril bundles was revealed with the aid of scanning electron
microscopy, and our observations have yielded new insights into the three
dimensional structure of the human dura mater spinalis. MATERIALS AND METHODS:
The preparations used were taken from the bodies of four persons who had died of
acute cardiac infarct at the ages of 70-78 years. The histories of these patients
gave no indications of earlier neurological, endocrine or septic illnesses. The
tissue examined was taken 8-12 h after death in all cases; it was immediately
fixed in glutaraldehyde and then processed for scanning electron microscopy in
the usual way. RESULTS: In the outermost (epidural) layer of the dura mater
spinalis the collagen fibres are bunched together in bands that run in all
directions. Elastic fibres 2 mm thick are woven into this three-dimensional
network of collagen systems. On the inside (the arachnoid side) thin collagen
fibres are fused into layers in such a way that the innermost layer resting on
the arachnoid has a smooth, shiny appearance comparable to that of a serosa. It
is attached to the actual dura with a supporting band of connective tissue. Rests
of the subdural neuroepithelium could contribute to the smooth appearance of the
superficial aspect. CONCLUSIONS: The outermost layer of the dura is made up
mainly of collagen fibres, which run in all three directions--longitudinal,
horizontal and transverse--both singly and in groups. These findings are at odds
with "classic" descriptions, according to which the fibres in the dura mater
spinalis all have a parallel course with a longitudinal orientation in tangential
sections.
PMID- 9645283
TI - [Polytrauma. Preclinical early support and shock management].
PMID- 9645284
TI - [Small-volume resuscitation in hypovolemic shock. Remarks on the work of U.
Kreimeier et al. Anaesthesist (1997) 46:309-328].
PMID- 9645285
TI - [Syringe- or lead change for TCI?].
PMID- 9645286
TI - [Post-spinal headache].
PMID- 9645287
TI - [A medium of the third kind: sensible use of the internet in anesthesia].
PMID- 9645288
TI - [Arterial hypertension: its impact on perioperative morbidity and mortality].
AB - Chronic hypertension is associated with structural as well as functional changes
of the vasculature, in particular of the coronary, cerebral and renal
circulation. It is important to realise that [1] functional changes are often the
result of structural changes, [2] the longer lasting the hypertension, the slower
and less complete the regression of structural changes, and [3] acute
"normalisation" of arterial pressure in long-standing hypertension may initially
induce functionally subnormal smooth muscle and/or cardiac activity because the
structure of the cardiovascular system is adapted to function at elevated
pressures. Despite a multitude of studies, the impact of hypertension on peri
operative morbidity and mortality remains controversial. There are as many
studies seeming to suggest that preoperative hypertension correlates with adverse
outcome as there are studies that fail to establish such a relationship. When
looking at the combined evidence, one is inclined to conclude that hypertension
is a predictor of "soft" outcomes (e.g. peri-operative myocardial ischaemia and
transient post-operative neurologic deficit) rather than an independent predictor
of "hard" outcomes (e.g. unstable angina, myocardial infarction and cardiac
death). In view of lack of convincing outcome data, it is impossible to recommend
a generally acceptable management strategy for the hypertensive patient.
Although, in general, a gradual reduction of blood pressure over a period of
weeks to months is the optimal therapeutic approach, we will be hard-pressed
delaying surgery for the sole purpose of "better blood pressure control". With
full appreciation and detailed knowledge of the pathophysiology of hypertension,
combined with sophisticated haemodynamic monitoring and interventions in the peri
operative period, acutely anaesthetising an inadequately treated hypertensive
patient will probably not adversely affect his outcome. Delaying surgery for
additional work-up may possibly improve outcome in patients with target organ
disease, evidence of secondary hypertension, in the most severe forms of
hypertension or sudden-onset hypertension.
PMID- 9645289
TI - [Measurement of the humidity of inspired air in ventilated patients with various
humidifer systems].
AB - INTRODUCTION: Humidification of inspired gas in artificially ventilated patients
positively influences mucociliary function and secretolysis. We performed this
study to examine the properties of heat and moisture exchangers in comparison
with hot water humidifiers and dry artificial ventilation. METHODS: We measured
inspired humidity with a special sensor in 41 patients after coronary artery
bypass grafting with cardiopulmonary bypass. Three Heat and Moisture Exchangers
(HME) and a hot water humidifier were used to humidity the inspired gas of
artificially ventilated patients. Humidity measurements were compared. RESULTS:
Hot water humidifiers produced the highest humidification (average of 38.4 mg/l,
37-43 mg/l); lowest humidification was produced by dry artificial ventilation
(average of 8.7 mg/l, 6-11 mg/l). Heat and moisture exchangers (HME) produced
humidity between 24 and 36 mg/l. Highest humidification was produced by HME
hygrobac s (average of 32.2 mg/l, 31-36 mg/l) and hygrovent s (average of 31.4
mg/l, 29-35 mg/l); lowest humidification was produced by HME hygroster (average
of 28.6 mg/l, 24-31 mg/l). Multifactorial analysis shows a significant impact of
the humidification method on the humidity of inspired gas. The multiple
comparison procedure (Tukey) shows significant differences (alpha = 0.05) between
all humidification techniques on inspired gas except the heat and moisture
exchangers hygrobac s and hygrovent s. CONCLUSIONS: Hygrobac s and hygrovent s
may be an alternative to hot water humidifiers. Further clinical studies of HMEs
and hot water humidifiers will be necessary to evaluate the influence of inspired
gas humidity on the outcome of artificially ventilated patients.
PMID- 9645290
TI - [Early and long-term results of percutaneous dilatation tracheostomy (PDT
Ciaglia) in 195 intensive care patients].
AB - PURPOSE: Tracheostomy is frequently required in the treatment of critically ill
patients to prevent the complications associated with prolonged translaryngeal
intubation. Tracheostomy may facilitate airway suctioning and improve patient
comfort in the process of weaning. The purpose of the study was to assess our
experience with PDT and to evaluate the complications in comparison with open
surgical tracheostomy which is associated with complication rates ranging up to
50%. METHODS: PDT was performed using the serial dilational technique described
by Ciaglia (percutaneous tracheostomy introducer set, Cook Critical Care) by
careful fibreoptic monitoring of the tracheal puncture and the tracheostomy tube
insertion. Complications related to the procedure and late effects were recorded.
RESULTS: 195 PDT were performed in adult intensive-care patients on prolonged
mechanical ventilation. In 182 cases (93.4%) placement of the tube was successful
without complications. Intraoperative complications occurred in 13 patients
(6.6%) including bleeding (5), superficial lesion of the tracheal mucosa (3),
pneumothorax (1) and others (4). After decannulation in 132 patients the
tracheostoma closed spontaneously and the cosmetic and functional results were
good. In 131 cases there was no clinical, radiographic and endoscopic evidence of
symptomatic tracheal stenosis. Only in one patient 6 weeks after decannulation a
relevant stenosis was seen. In 72 patients after median sternotomy no stomal
wound infection and no mediastinitis was observed. CONCLUSIONS: PDT is a safe and
practicable alternative technique which can be performed in the intensive-care
unit with a lower risk of complications than open surgical tracheostomy.
Endoscopic guidance prevents serious complications and apparently increases the
safety of this procedure.
PMID- 9645291
TI - [Desflurane versus isoflurane in geriatric patients. A comparison of psychomotor
and postoperative well-being following abdominal surgical procedures].
AB - PURPOSE: The new volatile anaesthetic agent desflurane has a significantly lower
blood-gas partition coefficient (0.42) than isoflurane (1.4), suggesting
excellent intraoperative control of anaesthesia and rapid emergence and recovery
from anaesthesia. However, only limited experience is available in geriatric
patients undergoing major abdominal surgery. METHODS: After approval by the local
ethics committee and with written informed consent, 52 patients (> or = 65 years
old, ASA class II or III) scheduled for major abdominal surgery were randomised
to receive either desflurane (DES) or isoflurane (ISO) for maintenance of
anaesthesia. After oral premedication with midazolam 3.75-7.5 mg, anaesthesia was
induced with etomidate 0.2-0.3 mg/kg and fentanyl 3 micrograms/kg. Vecuronium 0.1
mg/kg provided muscle relaxation for endotracheal intubation. All patients were
mechanically ventilated to maintain normocapnia. For maintenance of anaesthesia,
DES or ISO was administered in 60% N2O and additional boluses of fentanyl and
vecuronium were given as required. At the end of surgery, the neuromuscular
blockade was reversed with neostigmine 0.02 mg/kg and DES or ISO was discontinued
at the end of skin closure. Episodes of bradycardia and tachycardia and hypo- and
hypertension, the time from the end of anaesthesia to extubation, opening eyes,
squeezing hand, stating name and birthdate and to discharge from the recovery
room were recorded. Until 360 minutes after the end of anaesthesia, the recovery
of psychomotor functions was measured by means of simple reaction time tests,
critical flicker fusion test, labyrinth test, ball bearing test, short and long
term memory test and digit symbol substitution test. The patient's well-being was
documented with scores for pain, sedation and postoperative nausea and vomiting.
RESULTS: Demographic data in both groups was similar (Tab. 1). Anaesthesia was
significantly prolonged in the ISO group. No significant differences between
groups were found for MAC hours and the total dose of fentanyl and vecuronium
administered (Tab. 3). Intraoperative haemodynamics were comparable between both
groups (Tab. 4). No episodes of increases in heart rate or blood pressure
associated with rapid increases in DES concentration were seen. Early emergence
parameters were faster in the DES group (Tab. 5). When compared to ISO, the
overall test performance and testing ability was superior following DES.
Psychomotor tests showed significantly better results up to 240 minutes after the
end of DES anaesthesia (Tab. 7, Fig. 4). Comparing the postoperative well-being,
there were mild advantages for DES (Tab. 6, Fig. 1, 2, 3). However, time to
discharge of geriatric patients from the recovery room was significantly shorter
in the DES group (median 171 vs. 215 min., p < 0.05). CONCLUSION: Using a
balanced anaesthesia technique, we found desflurane as suitable as isoflurane for
geriatric patients. Additionally, due to the fast emergence from anaesthesia, an
improved cooperativity was found. In the DES group overall better postoperative
psychomotor performance resulted in a shortening of discharge times from the
recovery room. Hence, desflurane anaesthesia may be advantageous in geriatric
patients.
PMID- 9645292
TI - [Therapy with blood and blood components. 2. Perioperative management of
hemostatic disturbances with blood components].
PMID- 9645293
TI - [Early extubation following intracranial procedures: pro].
PMID- 9645294
TI - [Early extubation following intracranial procedures: contra].
PMID- 9645295
TI - [Effect of starvation on the ultrastructure of hepatocytes of Hemidactylus
frenatus (Lacertilia: Gekkonidae) with special emphasis on peroxisomes].
AB - The influence of starvation on hepatocyte ultrastructure of Hemidactylus frenatus
(Lacertilia: Gekkonidae) was investigated with special emphasis on peroxisomes.
Wall lizards (Hemidactylus frenatus) were sacrificed after different periods of
starvation and their livers were processed for standard transmission electron
microscopy. Peroxisomes were demonstrated by means of the 3,3'-diaminobenzidine
(DAB) cytochemical technique. A control group consisted of individuals which were
fed "ad libitum" with Tenebrio molitor larvae. After a 7-day period of starvation
the ultrastructural observation of hepatocytes disclosed a marked reduction of
glycogen and lipid inclusions associated with fragmentation of the endoplasmic
reticulum (ER). In later stages of starvation (14 and 25 days) ER proliferation
and partial reconstruction of glycogen aggregations were observed. Increasing
numbers of peroxisomes were arranged either in clusters (14 days) or in close
association with mitochondria, lipid droplets and elongated crystalloid
structures (25 days). Particularly noteworthy is the increasing cytochemical
response of these organelles to the DAB reaction, suggesting greater metabolic
activity of catalase. These data suggest that morphological and functional
plasticity of hepatocytes may contribute to adaptation of Hemidactylus frenatus
to prolonged starvation.
PMID- 9645296
TI - [Genesis and importance so-called inflammatory infiltration of the placenta. II.
Immunohistochemical findings].
AB - We investigated the morphologically distinct forms of inflammatory infiltration
of the placenta both histologically and immunohistologically (n = 24). Our
material included cases of membraneous inflammation (chorioamnionitis),
inflammatory infiltration of arteries in the chorionic membrane, basal and
intervillous placentitis. NACE staining was used to detect myeloid cells and
monoclonal antibodies (LCA, CD3, CD8, CD20, CD68). To detect lymphoid and
macrophageal cells we also measured the proliferation activity with MiB 1. In
cases of chorioamnionitis and subchorial demarcation and in the arteries of the
chorionic membranes the main inflammatory cell is the myeloid cell (most often
the mature neutrophil granulocyte). T-lymphocytes were only occasionally found.
In cases of intervillous placentitis, on the other hand, lymphocytic infiltration
predominates, consisting of T-lymphocytes which are mostly CD8 negative, and some
monocytes and macrophages. Basal inflammation in the demarcation zone was
characterized by T-lymphocytes. We interpret this as indicating basal
demarcation. According to our histological and immunohistological observations,
"asphyxial infiltrates" are abortive forms of a placental (bacteriological)
inflammation, possibly infective in origin. We do not consider asphyxial
infiltration to be a separate entity with its own causal pathogenesis.
PMID- 9645297
TI - Dentition and dentigerous bones in juveniles and adults of Polypterus senegalus
(Cladistia, Actinopterygii).
AB - Tooth types, their arrangement and the mode of tooth replacement were studied in
juvenile and adult specimens of Polypterus senegalus by means of scanning
electron microscopy of cleared and stained specimens as well as sections. All the
dermal bones of the oropharynx are almost completely covered with teeth except
for the angulare. The same is true for the branchial apparatus where only the
hyoid skeleton is toothless. The teeth are uniformly monocuspid and conical, but
can be classified according to shape and size into three types. These types and
the mode of tooth replacement are characteristic for each dermal bone. In some of
the jaw bones each tooth possesses a lingually situated replacement tooth. This
is true for the teeth of the premaxillary, the maxillary, and the dentary which
are arranged in a single line, and those of the dermopalatine, the coronoids, and
the vomer which are in several lines and graded in size. Replacement teeth of all
the other dentigerous elements develop on top of existing pulpal openings,
forming an anastomosing common pulpal complex only after resorption of the
previous tooth. The tooth plates of the dermal bones of the branchial apparatus
are connected by syndesmosis only to the perichondrally ossified and to the
cartilaginous or connective tissue material of the elements of the gill-arches.
The dentition and its association with the bones of the head in Polypterus
senegalus bear resemblances to advanced actinopterygians on the one hand (e.g.
differentiation of tooth-types, arrangement), but also some similarities to
living Amphibia (anchoring material and mode of replacement) on the other. The
accentuation of a single marginal line of large teeth in both, the outer and the
inner dental arcade of the jaws is a peculiarity of Polypterus that in a way
parallels the derived state of similar monolinear tooth arrangements in
Actinopterygii and Tetrapoda.
PMID- 9645298
TI - The electron microscopic morphology of the common carotid artery in rats.
AB - The common carotid arteries of normal adult rats were investigated electron
microscopically after tannic acid fixation. This fixation technique yields a
better demonstrability of the structures of the connective tissue, the basal
laminae and the surface coat of the cell membrane. The common carotid artery
represents a vessel of the elastic type. The intima consists of an endothelium
and a narrow gap of connective tissue (0.1-1 micron) which contains single
collagenous fibrils and small elastic structures. This space is only occasionally
as wide as 3 microns, especially beneath gaps of the internal elastic membrane.
In these areas, single cells and structures of densely packed filaments are
additionally observed which can neither be attributed to collagenous fibrils nor
to elastic fibres. The intima is demarcated from the outside by an internal
elastic membrane (1 micron) which shows a number of gaps. The media exhibits 3 to
4 elastic membranes without gaps. Smooth muscle cells of the contractile type
stretch in an oblique direction between these membranes, i.e. they are not
arranged in a circular or spiral manner. Most of their process-rich ends are
inserted directly into the elastic material and not via a basal lamina. Processes
from these smooth muscle cells, collagenous fibrils and elastic fibres are seen
in the intercellular spaces. The muscle cells are occasionally interlinked by gap
junctions. The basal lamina does not surround the muscle cells continuously. The
adventitia contains bundles of collagenous fibrils, fibrocytes, a few small
vessels and nerves with a perineuronal envelope. Nerves could not be demonstrated
in the media. The oblique course of the smooth muscle cells and the insertion
into the elastic membranes indicate that these cells do not predominantly
contribute to changes in the width of the lumen but also serve the stabilisation
and resetting of the elastic membranes. Contraction is probably induced by an
opening of stretch-dependent Ca2+ channels. Due to the interlinkage with gap
junctions, the muscle cells of one layer respond as a functional unit. Our
findings provide a morphological basis for elucidating commonly encountered
changes, such as smooth muscle migration through a normally interrupted inner
elastic lamina.
PMID- 9645299
TI - The structure of the skin of the tree frog (Hyla arborea arborea L.).
AB - The aim of the study was to investigate the structure of the skin of the adult
tree frog Hyla arborea arborea L. by scanning electron microscopy (SEM) and light
microscopy (LM). SEM observation shows that the skin from the dorsal part of body
is smooth whereas the ventral part has regular ridges and grooves. The
superficial layer of the skin consists of irregular shaped epidermal cells
covered with microridges differing on the dorsal and ventral skin. Two types of
gland outlets, funnel-type and collar-type, are seen on the surface of the
epithelium. The dorsal and ventral skin observed in LM contained three kinds of
glands: mucous glands, and two different types of serous glands, type I and II.
The mucous glands are small and located in the upper layer of the stratum
spongiosum of the connective tissue. The serous glands are large. Type I glands
with small secretory granules (1-3 microns) appear sporadically in both the
dorsal and ventral skin. Type II glands with large secretory granules (5-15
microns) are very numerous, particularly in the dorsal skin. Many capillaries
invaginate to the epidermis of the ventral skin facilitating absorption of water
in these sites. The lipid glands occurring in the skin of phyllomedusine frogs
are not observed in the skin of the tree frog.
PMID- 9645300
TI - Two types of three-dimensional structures formed by epithelial cell aggregates
from the rat ventral prostate in collagen gel culture. The amount of activated
charcoal for absorbing serum.
AB - Cells taken from the rat ventral prostate and cultured formed a tubular structure
inside the collagen gel in a medium containing activated charcoal-absorbed serum
after a 14-day incubation. This might suggest that the active substances of serum
could induce isolated epithelial cells to form such a spherical or tubular
structure, depending on the amount of activated charcoal used for the absorption
of serum.
PMID- 9645301
TI - Effects of a combined thermochemotherapy on the xenotransplanted human mammary
carcinoma MX-1. A light and transmission electron microscopic study.
AB - A thermochemotherapy (TCT), consisting of the administration of the alkylating
agent ifosfamide combined with whole body hyperthermia at 41 degrees C for one
hour applied to the xenotransplanted human mammary carcinoma MX-1, leads to a
complete remission within one week. This light and transmission electron
microscopical study concentrates upon the mechanisms of cell death and upon
therapy-induced changes in vasculature. These showed that TCT produces necrotic
rather than apoptotic cell death in xenotransplanted MX-1 tumors, whereas
apoptosis of endothelial cells was often found. We therefore conclude from our
experiments that TCT is a very powerful stimulus which directly impels MX-1 cells
towards coagulative necrosis, while endothelial cells, being probably more
resistant, often die by apoptosis.
PMID- 9645302
TI - Morphology and development of the postdiaphragmatic part of the sympathetic trunk
in the pig (Sus scrofa L.) during its prenatal period.
AB - The experiment was conducted on 36 swine fetuses divided into the three
developmental groups described by Marrable (1971). In the postdiaphragmatic part,
10 to 20 primary ganglia were found in the sympathetic trunk. They had fused with
the secondary structures, and hence the sympathetic trunks studied finally
consisted of 6-16 ganglia. It is remarkable that the higher number of primary
ganglia did not correspond with the higher number of secondary ones. The
variation in the number of secondary ganglia was mainly connected with the
interganglionic fusion occurring in the section studied. The standard variation
in the length of the sympathetic ganglia increased considerably with the age of
the fetuses as well as the analogous coefficient of variation. The analysis of
the statistical parameters referring to the ganglia of the investigated section
of the sympathetic trunk investigated indicated the growth of its developmental
dynamics, which did not occur until the terminal period of gestation.
PMID- 9645303
TI - A quantitative assessment of the jugular foramen.
AB - While it is generally accepted that the right jugular foramen is larger than the
left, little quantitative evidence exists on the exocranial and endocranial
openings of this foramen. The present study set out to clarify and quantify
measurements of the two openings. The dimensions of the exocranial and
endocranial openings of the jugular foramen and the volume and height of the
jugular fossa were examined in a total sample of 93 skulls from white and black,
male and female South Africans. The volume of the jugular fossa was determined
with the use of a dental impression material. The exocranial area of the right
jugular foramen was significantly larger (p < 0.05) than the left in the black
group, while the endocranial area of the right foramen was significantly larger
(p < 0.05) than the left only in black males. The height of the jugular fossa was
significantly larger (p < 0.05) on the right side only in the black group. The
volume of the jugular foramen was significantly larger (p < 0.05) on the right
side only in females of both groups. Although the jugular foramen is generally
larger on the right side than on the left, its size as well as the volume and
height of the jugular fossa is variable in different groups and sexes.
PMID- 9645304
TI - [Topographic and anatomic study of lateral upper arm transplants].
AB - An anatomic and topographic study of the lateral upper arm free flap for the
clinical use in reconstruction. Defects of the laryngopharynx and the oral cavity
after cancer ablation are increasingly reconstructed by free microvascular
anastomosed tissue transfer. Besides the jejunum transplant we use the free
radial forearm flap frequently. This flap is suitable for restoring intraoral and
pharyngeal integrity. Major disadvantages are the requirement of a skin graft to
obtain wound closure and the cosmetic deformity. The lateral upper arm free flap
is intended as alternative method for the fasciocutaneus tissue transfer. Based
on our dissection of ten cadavers we demonstrate the anatomy of the flap, the
harvesting technique, and present data of vascular pedicle length, vessel
calibers, and flap size. The vessel calibers of the profound brachial artery (X =
2.5 mm) and its terminal branch, the posterior radial collateral artery (X = 1.8
mm), are comparable to the radial artery. The pedicle length can be extended up
to 13 cm by using a lateral approach. The subcutaneous tissue volume was 1.3 cm
in average, and compared to the radial flap rather thick. Because of his bulky
and strong fascia the lateral arm flap seems to be useful as a fascia-fat flap in
facial augmentation or as a fascia flap in soft tissue reconstruction.
Disadvantageous are the difficult dissection technique and the loss of
sensitivity on the lateral aspect of the forearm. Where a fasciocutaneous flap is
indicated, we prefer the radial forearm flap.
PMID- 9645305
TI - [Neurovascular infrahyoidal myofascial flap. Anatomic and topographic study of
the innervation and blood supply].
AB - The neurovascular infrahyoidal myofascial flap: An anatomical and topographical
study of the innervation and blood supply. 15 cadavers had bilaterally been
examined for the topography of the upper thyroid artery and vein and of the lower
cervical ansa, as an axial bundle of vessels and nerves for the infrahyoidal
myofascial flap. With the injection of methylene blue the vascular territories of
the upper thyroid artery had been demonstrated. The upper thyroid artery and vein
could be found in all cases. This artery was deriving in 47% from the external
carotid artery, in 30% from the bifurcation and in 23% from the common carotid
artery. The vein flowed in 43% into the facial vein and in 37% into the internal
jugular vein. In the remaining 20% several segmental veins were found, which
flowed into the jugular vein separately. In case of a far caudally situated
vascular bundle the radius of rotation can be limited in cranial direction. The
voluntary innervation of the muscles of this flap is derived from the lower
cervical ansa. The upper radix of the ansa can be found 1 cm in latero-cranial
direction of the greater horn of the hyoid bone, where it is separating from the
hypoglossal nerve. The upper thyroid artery is supplying the infrahyoidal
musculature in the whole extension from the hyoid bone to the sternum. Therefore
it is possible to develop a myofascial flap of 3.5 cm x 11.5 cm in size, which is
pedicled at an upper vascular and nerval bundle. Depending on the radius of
rotation defects of the floor of mouth, of the tongue and of the oro- and
hypopharynx can well be covered with this new neurovascular myofascial flap.
PMID- 9645306
TI - Neuronal pathways from foot pad afferents to hindlimb motoneurons in the low
spinalized cats.
AB - Experiments were performed on 16 adult spinalized (L2) cats. Postsynaptic
potentials (PSPs) produced by electrical stimulation of afferent nerves
innervating foot pads were recorded from hindlimb motoneurons innervating the
following hindlimb muscles: the posterior biceps and semitendinosus (PBSt),
anterior biceps and semimembranosus (ABSm), lateral gastrocnemius and soleus
(LGS), medial gastrocnemius (MG), plantaris (P1), tibialis anterior (TA),
popliteus (Pop), flexor digitorum longus and flexor hallucis longus (FDHL) and
peroneus longus (Per.l). The rate of occurrence of different types of PSPs
(EPSPs, IPSPs and mixed PSPs), the size of the PSPs and their central latencies
were analyzed for each group of motoneurons to identify the neural pathways from
the afferents innervating foot pads to hindlimb motoneurons. The rates of
occurrence of different types of PSPs did not depend on the foot pad stimulated
in PBSt, ABSm and LGS motoneurons, but for other groups of motoneurons their
rates of occurrence depended on the foot pad stimulated. It was often noted that
the size of PSPs in the same motoneurons differed according to the foot pad
stimulated. Measurements of the central latencies of the PSPs indicated that the
shortest neural pathways for EPSPs and IPSPs were disynaptic (central latencies <
1.8 ms). The functional role of neuronal pathways from afferent nerves
innervating foot pads to hindlimb motoneurons could be to maintain stability of
the foot during different postural and motor activities.
PMID- 9645307
TI - Lipid peroxidation and phospholipid composition in rat brain regions after
ischemia and in early perfusion periods.
AB - Lipid peroxidation products (LPPs) and phospholipid composition were studied in a
model of four-vessel occlusion in rats in homogenates of cortex, striatum and
hippocampus after 30 min forebrain ischemia and following 1, 5, 10, 15, 30 and
180 min of recirculation. Major modification of LPPs was found after shorter
reperfusion time, 5 min in hippocampus and 15 min in cortex and striatum when
compared to control, while a slight decrease in the level of LPPs in the striatum
and hippocampus was detected after longer (30 and 180 min) intervals. However,
significant decrease was found in the homogenates of cortex. The results obtained
from enhanced iron-dependent peroxidation in homogenates of frontal and occipital
cortex indicated marked susceptibility to lipid peroxidation in the tissue
subjected to 30 min ischemia and after 15 min of recirculation. The level of DG +
PA was significantly higher during ischemia in the striatum, while increased
hydrolysis of PI and DG + PA concentrations in the cortex, PI and PE levels in
the striatum and PE and PS in the hippocampus after 30 min of ischemia were
found. After 15 min of reperfusion considerably higher degradation of almost all
phospholipids was found within all brain regions studied. The irreversibility of
changes in PS, PE and SM was noted in the hippocampus after longer reperfusion
periods. Our results indicate that the correlation between the lipid peroxidat
ion product formation and phospholipid hydrolysis does exist, and, moreover,
early reperfusion period seems to be highly critical in the development of
ischemia-reperfusion induced neuronal damage.
PMID- 9645308
TI - Cervical and cerebellar projections of lamina VII and VIII neurones of the S2
segment in the cat's spinal cord.
AB - Dual projections to the sixth cervical segment and to the cerebellum were
electrophysiologically investigated in neurones from the second sacral segment of
the spinal cord in cats under chloralose anaesthesia. 49 neurones were
antidromically identified following stimulation of the ipsilateral and
contralateral spinal gray matter of the C6 segment and the contralateral inferior
cerebellar peduncle (coRB), 28 of the total sample projected to the C6
bilaterally, 17 contralaterally and 4 ipsilaterally. 24 neurones of bilateral or
contralateral projection to the C6 could be additionally activated from the coRB.
The cells were distributed in Rexed's laminae VII and VIII with neurones
projecting to the cerebellum located more medially. Conduction velocities of
axons ascending in lateral funiculi were comprised in the range 42-96 m/s and the
decrease was observed in some cases when compared distal and proximal parts of
axons. No differences were found when compared values for neurones with or
without cerebellar projection. It is suggested that both propriospinal and
supraspinal projections of the investigated neurones take part in hindlimb
forelimb coordination.
PMID- 9645309
TI - Relation between fibre composition and daily duration of spontaneous activity in
ankle muscles of the cat.
AB - This study concerns the relation between use and fibre type composition among
limb muscles. The histochemical properties were investigated for ankle muscles
from cats that had previously been studied in 24 hr electromyographic (EMG)
recordings of daily spontaneous activity. We then reported average daily "duty
times" (i.e. the percentage of total sampling time filled with EMG activity) of
1.9% for extensor digitorum longus (EDL), 2.1 and 4.0% for anterior and posterior
sites of tibialis anterior (TA), 6.6 and 9.5% for anterior and posterior sites of
peroneus longus (PL), and 13.9% for soleus (SOL). In the present experiments,
muscles from which these data had been obtained were sectioned in a cryostat and
stained for myofibrillar ATPase. Fibres were classified as type I (presumably
slow) or II (presumably fast), the latter fibres being further categorized as
IIA, IIB and a minor portion of transitional IIAB fibres. As expected, SOL was
100% type I. Among the muscles of mixed fibre-type composition ("mixed muscles"),
a statistically significant difference in the mean percentages of type I fibres
was found between TA or EDL (2.9-6.0%) vs. PL (11.8-14.6%). For TA the percentage
of type I fibres was higher in posterior (deep) than in anterior (superficial)
sampling regions; for PL no clear antero-posterior difference was found. A
significant correlation was obtained between the percentage of type I fibres and
the total duration of daily activity recorded from corresponding mixed muscle
sites (5 different recording sites in 4 cats, totally 15 cases of successfully
combined physiological and histochemical measurements, r = 0.76, P < 0.001).
Similarly, within TA the total duration of daily activity was higher for sites
with high (posteriorly) than for those with low (anteriorly) percentages of type
I fibres. IN CONCLUSION: a "coarse-grain" relationship was found between fibre
type composition and the duration of daily activity among mixed muscles. Possible
mechanisms underlying this relationship are discussed.
PMID- 9645310
TI - Microinjections into the pedunculopontine tegmentum: effects of the GABAA
antagonist, bicuculline, on sleep, PGO waves and behavior.
AB - Neurons in the peribrachial region (PB) at the pontine border are implicated in
the generation of ponto-geniculo-occipital (PGO) waves, which appear
spontaneously during rapid eye movement sleep (REM) and in association with
alerting behaviors during waking, as well as in the regulation of REM itself. It
has been hypothesized that PGO-related bursting in a subpopulation of these
neurons results from low threshold spikes triggered by phasic hyperpolarizations
or by excitatory inputs reaching a steadily hyperpolarized neuron. The
hyperpolarization necessary for triggering the low threshold spikes may come from
local GABA neurons or from GABAergic input into PB. To test the hypothesis that
antagonizing GABA would alter PGO wave generation and/or behavioral state, we
microinfused, in cats, the GABAA antagonist, bicuculline, locally into PB and
monitored behavior, behavioral state and PGO waves recorded in the lateral
geniculate bodies. Bicuculline produced no significant alteration in PGO wave
activity. In 3 cats, bicuculline produced behaviors ranging from spontaneous
orienting and startle (4 cats) to flight behaviors (2 cats) and aggressiveness (2
cats), an effect probably due to diffusion into the central gray region. Thus,
the results do not support a GABAA-ergic role in PB in the generation of PGO
waves.
PMID- 9645311
TI - Excitatory amino acids as neurotransmitters of corticostriatal projections:
immunocytochemical evidence in the rat.
AB - The retrograde transport of a tracer has been combined with peroxidase
immunocytochemistry to verify whether corticostriatal (CS) neurons contain in
their cell bodies high levels of glutamate (Glu) and aspartate (Asp). Injections
of WGAapoHRP-Au in the caudate/putamen of adult rats produced retrograde labeling
of a large number of layer V neurons of wide regions of the ipsilateral cerebral
cortex; fewer labeled neurons were also found on the contralateral side. In all
experiments, most CS neurons were seen in the agranular frontal cortex, in both
the medial and the lateral subdivisions. Moreover, numerous retrogradely labeled
neurons were observed in the cingulate cortex and in the granular parietal
cortex, depending on the location of the injection site in the various
experiments. The majority of CS neurons examined were immunostained using
antibodies against glutaraldehyde-conjugates of Glu or Asp. Glu immunopositive
neurons resulted 52-61% of CS neurons. Asp immunopositive neurons ranged between
53% and 62%. In the cortical tissue where Glu and Asp antisera were visualized
simultaneously, up to 96% of the CS neurons were immunostained. The latter
finding indicates that the populations of Glu and Asp immunopositive neurons are
largely segregated and that virtually all cortical neurons projecting to the
striatum contain high concentrations of Glu and/or Asp, thus corroborating the
hypothesis that CS projections use excitatory amino acids as neurotransmitters.
PMID- 9645312
TI - Inflammation of the bronchi in broiler chickens, associated with barn dust and
the influence of barn temperature.
AB - Broiler chickens were raised in separate rooms kept at temperatures of either 27
C or 16 C from 28 through 39 days of age. At the high temperature mouth breathing
was recorded, but it was absent at the lower temperature. The number of dust
particles in the air was greater in the warm rooms. More than 50% of the chickens
in warm rooms had microscopic lesions in the bronchi of their lungs, whereas
fewer than 5% of chickens in cold rooms had such lesions. Large dust particles
were visible in some of the lesions. It was postulated that the increased
incidence of lung lesions in chickens from warm rooms was due to mouth breathing
rather than the higher dust levels in the air of these rooms.
PMID- 9645313
TI - Experimental infection and transmissibility of Mycoplasma synoviae with delayed
serologic response in chickens.
AB - Fifteen mycoplasma-free chickens were contact exposed to five chickens that had
been experimentally infected with one of three different strains (two field
strains and one laboratory strain) of Mycoplasma synoviae (MS). Culture and
polymerase chain reaction (PCR) were positive by 3 days postinoculation (PI) in
the experimentally infected birds. Lateral transmission was found by 7-14 days
postexposure. Positive serum plate agglutination (SPA) results were detected 3-4
wk after positive culture and/or PCR in individual birds. By 42 days PI, all the
birds in the groups exposed to field strain K1858 or K3344 had become infected as
determined by culture and PCR, whereas only half of the birds in the group
exposed to laboratory strain WUV1853 had become infected. Because of the
unanticipated lack of seroconversion to hemagglutination inhibition (HI) and
enzyme-linked immunosorbent assay (ELISA) in infected chickens, the study was
extended. Each group was split into two groups of 10 birds each, one of which was
vaccinated with a live B1/LaSota Newcastle disease (ND) vaccine virus to
determine if a viral respiratory challenge might incite a stronger antibody
response to the mycoplasma infection. All the birds were tested for
seroconversion 14 and 21 days later. Of the birds vaccinated for ND, a slightly
greater number were MS positive by SPA than the nonvaccinated birds. This effect
was not present 21 days after vaccination, and there was no significant
difference in the MS HI results from these groups, suggesting that the viral
respiratory infection had little direct impact on seroconversion. The virulent
field strain (K3344) elicited a stronger MS antibody response than the other
strains. All results from the MS ELISA were negative in all groups through 9 wk.
Positive results from PCR analysis correlated well with culture results, whereas
serologic tests did not detect MS infection for several weeks. Monitoring
programs solely dependent on seroconversion may be inadequate for diagnosis and
control of mycoplasma infections.
PMID- 9645314
TI - Inhibition of Eimeria tenella development in vitro mediated by chicken
macrophages and fibroblasts treated with chicken cell supernatants with IFN-gamma
activity.
AB - Pretreatment of chicken macrophages or fibroblasts with supernatants from
concanavalin A-stimulated spleen cells or from the virus-transformed cell line
reticuloendotheliovirus as source of interferon gamma (IFN-gamma) slows down
subsequent sporozoite replication in the cells. To identify the presence of IFN
gamma, we combined four typical activities of IFN-gamma: inhibition of cytopathic
effect of vesicular stomatitis virus on IFN-gamma-treated fibroblasts, cytostatic
activity of IFN-gamma-activated macrophages, induction of major
histocompatibility complex II antigen expression on IFN-gamma-activated
fibroblasts and macrophages, and induction of nitrite production in macrophages.
We have shown that chicken fibroblasts and macrophages possess a microbiostatic
capacity once they are able to prevent the otherwise unchecked intracellular
replication of Eimeria tenella following activation with culture supernatants
identified as containing a strong IFN-gamma activity.
PMID- 9645315
TI - Efficacy of inactivated H5N2 influenza vaccines against lethal
A/Chicken/Queretaro/19/95 infection.
AB - The control and eventual eradication of H5N2 influenza virus from domestic
poultry in Mexico is dependent on the use of avian influenza (AI) vaccine
strategies. This study was performed to determine the amount of hemagglutinin
(HA) antigen required to control the signs of disease from a highly pathogenic
H5N2 influenza virus (A/Chicken/ Queretaro/19/95) and the amount of antigen
required to prevent shedding of virus from vaccinated birds. Six commercial
inactivated water in oil H5N2 vaccines available in Mexico were compared with
standardized vaccines to assess their efficacy. The amount of HA required to
prevent the signs of disease from A/Chicken/Queretaro/19/95 influenza virus was
approximately 0.4 microgram per dose. Each of the six commercially available
vaccines prevented disease signs, and half of the vaccines significantly reduced
viral shedding from vaccinated birds. There is a need for standardization of AI
virus vaccine, and the antigen content should be increased in some of the
commercially available AI vaccines in Mexico.
PMID- 9645316
TI - Comparison of Salmonella typhimurium challenge models in chickens.
AB - Experimental infection of chickens with controlled quantities of Salmonella
typhimurium is often achieved by administration of a single oral inoculum of live
bacteria to caged chickens. However, this method is a poor simulation of the
natural process of S. typhimurium infection in the field, making the practical
application of results obtained under such conditions tenuous. This experiment
was designed to evaluate the use of horizontal transmission for the
challenge/infection of chickens with S. typhimurium with the expectation that it
may more closely resemble the natural situation and, therefore, the in-field
physiological response of chickens. Further, the experiment allowed for
comparison of both the kinetics and magnitude of the mucosal immune response
following each mode of challenge by exposing the chickens to challenge by placing
them on litter with S. typhimurium-infected seeder birds. Overall, birds
challenged via seeded litter exhibited a slower rate of infection and a more
gradual increase in serum antibody production compared with birds receiving a
single oral inoculum.
PMID- 9645317
TI - Differentiating turkey postvaccination isolants of Pasteurella multocida using
arbitrarily primed polymerase chain reaction.
AB - The chromosomal DNA of 29 field isolants of Pasteurella multocida from commercial
turkey farms in Missouri and the avirulent Clemson University (CU) and M-9
vaccine strains of P. multocida were tested using the arbitrarily primed
polymerase chain reaction (AP-PCR) in combination with 32P-labeled deoxycytidine
triphosphate (dCTP) and high-resolution gel electrophoresis. The 29 field
isolants of P. multocida were isolated from outbreaks of fowl cholera in turkey
flocks in which vaccination with the CU vaccine had been performed within 2 weeks
of the isolation, and it was suspected that the outbreak could have been due to
the use of the live CU vaccine. The results of this study showed that: 1) the use
of the live CU vaccine can lead to the isolation of the vaccine strain if the
outbreak occurs within 2 weeks of vaccination; 2) a higher proportion of field
isolants collected during 1983 and 1984, when the usage of the CU vaccine strain
was highest on Missouri turkey farms, had PCR-amplified product profiles similar
or identical to those of the CU vaccine strain compared with the period between
1987 and 1992, when its use was less; and 3) there was no relationship between
the PCR-amplified product profiles and the serotype.
PMID- 9645318
TI - Serotype identification of avian infectious bronchitis virus by RT-PCR of the
peplomer (S-1) gene.
AB - The S-1 peplomer gene sequences of 31 strains of avian coronavirus infectious
bronchitis virus (IBV) from North America, Europe, and Australia were compared to
identify common and unique regions for possible diagnostic applications. S-1
sequences that were conserved among serotypes and sequences that were variable
between serotypes were identified. Based on conserved S-1 gene sequences,
"general" degenerate oligonucleotide primers were designed that amplified IBV
genomic RNA by the reverse transcriptase polymerase chain reaction (RT-PCR)
procedure regardless of serotype. Primers specific for IBV serotypes
Massachusetts, Connecticut, Arkansas, JMK, Delaware (DE/072/92), and California
(CA/633/85) were designed from regions of the S-1 gene exhibiting extensive
sequence hypervariability. The ability to identify these six serotypes of IBV by
RT-PCR was demonstrated by testing the serotype-specific primers on a panel of
unknown samples that included 30 reference strains and field isolates previously
characterized by virus neutralization (VN). The use of serotype-specific primers
in RT-PCR provides a rapid and accurate means of identifying IBV.
PMID- 9645319
TI - Cellulitis in broiler chickens: epidemiological trends, meat hygiene, and
possible human health implications.
AB - The present work evaluates trends in the incidence of cellulitis during the last
decade using Canadian National Poultry Condemnation Records. In 1986, only 0.048%
of the total slaughter broilers were condemned as a result of cellulitis lesions.
Over the next 10 yr, steady increments in cellulitis condemnations were observed,
and between 1986 and 1996, the percentage of cellulitis condemnation increased
11.8-fold. In 1996, more than 2.6 million broilers (0.568% of total slaughter)
were condemned due to cellulitis; this constituted 30.1% of total condemnations,
making it the number one condemnation category in 1996. In the context of dynamic
increase in cellulitis, the problems concerning meat hygiene and possible health
risk to the consumer are deliberated.
PMID- 9645320
TI - Latent turkey herpesvirus infection in lymphoid, nervous, and feather tissues of
chickens.
AB - In earlier studies, we found that a late gene product, glycoprotein B (gB) was
highly expressed in lymphoid tissues of chickens inoculated with turkey
herpesvirus (HVT). The objectives of the present study were twofold. First, we
wanted to expand on our previous research and determine if gB expression declines
or disappears during later time periods of HVT infection. Second, we wanted to
correlate gB expression with presence of HVT, i.e. if gB expression is absent,
can HVT still be detected? Fifteen 1-day-old chicks were inoculated by
intraperitoneal inoculation with 2000 plaque forming units of strain FC126 HVT.
Thymus, spleen, bursa, brachial plexus, sciatic plexus, and feather tips were
harvested at 21, 28, 35, 70, and 105 days postinoculation (PI). Brachial plexus
and sciatic plexus were examined at 21, 28, and 35 days PI, and feather tips were
examined at 21 and 28 days PI. An indirect immunofluorescence assay was used to
detect HVT gB expression, and an in situ hybridization assay was used to detect
HVT. At 21 days PI, gB expression was present in the thymus, spleen, and bursa.
At 28 and 35 days PI, gB expression was detected in the thymus and spleen. At 70
days PI, gB expression was detected only in the spleen, and at 105 days PI, gB
expression was not detected in any of the lymphoid tissue (thymus, spleen, or
bursa). gB expression was not detected in the brachial plexus, sciatic plexus, or
feather tips at any of the five time points. The bursa contained HVT only at 21
and 28 days PI. However, HVT was demonstrated in all other tissues from 21 to 105
days PI. Progression from a productive HVT infection to a latent HVT infection
results in the loss of gB expression. Throughout this progression, a region of
the HVT genome can be detected by appropriate methods.
PMID- 9645321
TI - Pen trial studies on the use of live vaccines to displace virulent Mycoplasma
gallisepticum in chickens.
AB - Groups of 10 8-wk-old chickens that had been vaccinated 4 wk previously with the
F strain, ts-11, or 6/85 strain of Mycoplasma gallisepticum (MG) were challenged
by placing them in contact with 20 chickens that had been previously infected
with the virulent R strain of MG. Each month, the 10 oldest chickens were removed
from each pen and replaced with 10 vaccinated chickens to return the total number
of chickens in each pen to 30. Chickens were bled and cultured for MG prior to
contact challenge and at the time of removal from the challenge pen. The strain
of all MG isolates was determined by rapid amplified polymorphic DNA. All vaccine
strains were isolated from tracheas prior to contact challenge, but colonization
by the 6/85 vaccine strain was inconsistent. Beginning with the group placed in
contact 3 mo after the initiation of the study, F strain had begun to displace
the R challenge strain. By the eight month, F strain had completely displaced the
R strain in that pen. However, neither strain ts-11 nor 6/85 was able to displace
the R strain under the conditions of this study.
PMID- 9645322
TI - Recombinant chicken interferon-gamma-mediated inhibition of Eimeria tenella
development in vitro and reduction of oocyst production and body weight loss
following Eimeria acervulina challenge infection.
AB - Recombinant chicken interferon-gamma (chIFN-gamma) was produced in CHO-K1 or
Spodoptera frugiperda (SF9) insect cells by transfection with a pcDNA vector or
recombinant baculovirus (SF9-interferon-gamma [IFN-gamma] carrying the chIFN
gamma gene. A rabbit antibody against a synthetic peptide corresponding to an
immunogenic portion of chIFN-gamma recognized a 22-23-kDa band in SF9-IFN-gamma
cell extracts by western blot analysis. Biological activity of recombinant chIFN
gamma was shown by its inhibition of vesicular stomatitis virus-induced
cytotoxicity of chicken embryonic fibroblast cells in vitro. To investigate the
role of chIFN-gamma during Eimeria infection, CHCC-OU2 chicken cells either
pretreated with chIFN-gamma or stably transfected with the chIFN-gamma gene were
infected with Eimeria tenella sporozoites. IFN-gamma demonstrated significant
reductions in intracellular sporozoite development without affecting sporozoite
invasion of host cells. Furthermore, chickens treated with recombinant chIFN
gamma showed decreased oocyst production and significant improvement in body
weight gain following Eimeria acervulina challenge infection. These results
provide the first direct evidence that chIFN-gamma exerts an inhibitory effect
against Eimeria and provides a rational basis for use of this cytokine as a
vaccine adjuvant against coccidiosis.
PMID- 9645323
TI - Airborne transmission of Salmonella enteritidis infection between groups of
chicks in controlled-environment isolation cabinets.
AB - Although direct contact with infected birds and indirect contact with
contaminated environmental surfaces are known to be important factors in the
dissemination of Salmonella enteritidis in poultry flocks, the potential role of
airborne transmission is less clearly defined. This study considered the
mechanism by which S. enteritidis might spread between groups of chicks housed in
controlled-environment disease transmission cabinets, separated by an unoccupied
space that prevented any direct or indirect contact. Airflow in these cabinets
was directed across the unoccupied area from one ("upstream") group of chicks to
the other ("downstream") group. In each of four replicate trials, two groups of
25 chicks were placed in the upstream ends of transmission cabinets and orally
inoculated with S. enteritidis at 1 week of age. One day later, 25 1-day-old
chicks were placed in the downstream end of each cabinet. When chicks were
removed and sampled at 3 and 7 days postinoculation, S. enteritidis was found on
the feathers of 77% of the downstream chicks. Moreover, 33% of the downstream
chicks became infected with S. interitidis. The comparative frequencies of
recovery of S. enteritidis from various downstream sampling sites suggested that
infection was apparently transmitted principally by oral ingestion, perhaps from
environmental surfaces contaminated by airborne movement of the pathogen.
Reducing the airborne movement of S. enteritidis in poultry houses should thus
help limit the spread of infection within flocks and thereby diminish the
incidence of production of contaminated eggs.
PMID- 9645324
TI - Genetic heterogeneity in the VP2 gene of infectious bursal disease viruses
detected in commercially reared chickens.
AB - The genetic heterogeneity of infectious bursal disease virus (IBDV) vaccine
strains was compared with IBDV detected in bursa tissue of commercially reared
chickens. The vaccine strains tested represented classic viruses from the United
States, South Africa, England, and France plus variant viruses from the United
States. Bursa tissue samples used for the detection of IBDV from commercially
reared chickens were from the United States. Genetic heterogeneity was examined
using restriction fragment length polymorphisms (RFLP) of a 743-bp fragment of
the VP2 gene that was amplified using reverse transcriptase/polymerase chain
reaction (RT/PCR). The RT/PCR products were digested using restriction enzymes
BstNI and MboI. On the basis of RFLP profiles, viruses were placed into molecular
groups. Thirty-eight vaccine and laboratory strains of IBDV were placed into five
molecular groups. Groups 1 and 2 contained variant viruses, groups 3 and 4
contained classic viruses, and group 5 contained Lukert/Edgar strain classic
viruses. In contrast to these five molecular groups, 22 molecular groups were
observed for 70 IBDV-positive samples from U.S. chicken flocks. Twenty-two of the
70 IBDV-positive samples were placed into molecular groups 1 (2 samples), 2 (18
samples), and 5 (2 samples). Nineteen new RFLP profiles that did not match the
five molecular groups observed for vaccine strains were detected. No viruses were
observed to have RFLP profiles like molecular groups 3 and 4 observed in the
vaccine strains. The genetic heterogeneity was greater among IBDV strains
circulating in commercially reared poultry compared with vaccine strains of the
virus.
PMID- 9645326
TI - Potential for transmission of the finch strain of Mycoplasma gallisepticum
between house finches and chickens.
AB - Although Mycoplasma gallisepticum (MG) is established in house finch (Carpodacus
mexicanus) populations in at least 33 states, the potential risk of MG
introduction to domestic poultry by infected finches currently is unknown. The
objectives of this study were to determine if chickens could be infected with the
finch strain of MG via direct, across-wire, and proximity (across-room) contact
with naturally infected house finches and to determine if house finches could be
infected through direct contact with experimentally infected chickens. Chickens
were infected with the finch strain of MG through direct contact with naturally
infected house finches, a determined by seroconversion (80%), polymerase chain
reaction (PCR) (20%), and culture of MG (30%). Clinical disease was not observed
in infected chickens. Isolates from chickens were identified as the original
finch strain by arbitrary primed PCR. Transmission required an extended period of
direct contact (10 wk) with infected finches, and no evidence of MG infection was
detected in chickens exposed to infected finches across wire or across the room.
Evidence of contact transmission of MG from infected chickens to house finches
was limited to positive serum plate agglutination results, and infection could
not be confirmed by PCR or culture. Results suggest that minimal biosecurity
measures that restrict direct contact between chickens and house finches should
significantly reduce the potential for MG transmission between these species.
PMID- 9645325
TI - Molecular characterization of seven Chinese isolates of infectious bursal disease
virus: classical, very virulent, and variant strains.
AB - Seven infectious bursal disease virus (IBDV) strains isolated from China have
been characterized in this study, including a classical strain CJ801, an
attenuated strain GZ911, a variant strain GZ902, and four very virulent strains
G9201, G9302, F9502, and HK46. With the use of reverse transcription-polymerase
chain reaction, the full-length VP2 genes were amplified and the hypervariable
regions were sequenced. Protein sequences of the hypervariable region (a.a. 143
382) of the field isolates confirmed their identities. CJ801 has the highest
identity to the classical strains STC and 52/70. GZ902 has the highest identity
to the American variant strains A, E, and GLS, and they share unique amino acid
residue at positions 249K and 254S, which are not present in standard serotype 1
strains. Attenuated strain GZ911, like other cell culture-adapted strains, has
substitutions at positions 279(D to N) and 284 (A to T) as well as in the serine
rich heptapeptide region. Hence, these substitutions may take an important role
in the reduced virulence of these strains. The four very virulent strains have
the highest identity to the European very virulent strain UK661 and Japanese
strain OKYM. These strains share unique amino acid residues at positions 222A,
256I, and 294I, which are not present in other less virulent strains. The very
virulent strains isolated in Guangdong (G9201, G9303) and Fujian (F9502)
Provinces have one to five amino acid substitutions at the two hydrophilic
domains of VP2 comparing with UK661 and OKYM, indicating that new very virulent
strains are evolving. Phylogenetic analysis suggests that Chinese very virulent
IBDVs and European very virulent strains are derived from similar origin.
PMID- 9645327
TI - The effect of inoculating Enterococcus faecalis into the yolk sac on chick
quality and maternal antibody absorption.
AB - Four hundred thirty-two 1-day-old specific-pathogen-free chicks were randomly
divided into 36 groups of 12. All chicks were given 0.2 ml of Newcastle disease
antiserum (hemagglutination-inhibition [HI] titer 1:5120) by injection into the
yolk sac at hatch. Half of the groups received 0.2 ml of Enterococcus faecalis
(4.0 x 10(8) colony-forming units/ml) by injection into the yolk sac at hatch
(treatment). The remaining 18 groups received no bacteria (control). Two
treatment groups and two control groups were weighed, bled, killed, and yolk sac
weighed daily for the first 9 days of life. Feed was weighed at placement and at
the end of the trial. Blood was tested for packed cell volume (PCV), total plasma
protein, and Newcastle disease HI titer. No significant difference was observed
between treatment and control groups for chick body weight, PCV, and feed
consumption. Total plasma protein and retained yolk weight were significantly
higher for treatment groups over control (P < 0.01 and P < 0.0001, respectively).
Also, the geometric mean serum HI titer (log2) for Newcastle disease antibody was
significantly higher in the control chicks vs. the treatment chicks (P < 0.01).
PMID- 9645328
TI - Infectious bronchitis virus antibodies in tears and their relationship to
immunity.
AB - Antibodies to infectious bronchitis virus (IBV) in chicken tears were
investigated to determine if they could be used as an indicator of protective
immunity. Antibody production in tears and serum was measured by enzyme-linked
immunosorbent assay (ELISA) in specific-pathogen-free (SPF) white leghorn and
broiler chickens vaccinated with a live attenuated vaccine containing the
Massachusetts (Mass) Connaught strain of IBV. The effect of virulent infectious
bursal disease virus (IBDV) infection on antibody production in tears was also
evaluated. Immunity was assessed by challenging the chickens with Mass 41 and
performing tracheal swabbings 5 days later. In addition, tears were also
evaluated for virus-neutralizing (VN) antibodies to IBV. Following eyedrop
vaccination, anti-IBV antibodies were consistently detected by ELISA in tears
prior to and in higher concentrations than in the sera of SPF white leghorn and
broiler chickens. Maternal IBV antibodies were present in the tear secretions of
broiler chickens but in lower concentrations than in sera. Infection of SPF
chicks with a virulent and immunosuppressive strain of IBDV at 1 day of age
greatly reduced IBV ELISA antibody production in tears as well as serum compared
with infection of chickens with IBDV at 14 days of age. IBV ELISA and VN antibody
levels in tears were not accurate indicators of IBV immunity as determined by
challenge with Mass 41. High tear IBV antibody titers were observed in some
chickens determined to be susceptible to IBV challenge and low tear titers were
detected in some protected chickens. This finding suggests that mechanisms other
than antibody-mediated immunity in tears are important in viral clearance
following challenge.
PMID- 9645329
TI - Detection of avian leukosis virus subgroup J using the polymerase chain reaction.
AB - A polymerase chain reaction (PCR) assay was developed for the detection of avian
leukosis virus strain J (ALV-J) in chickens. Primers were based in the E element
and the 3' terminus of the long terminal repeat of proviral ALV-J. PCR products
were amplified from genomic DNA extracted from chicken embryo fibroblasts (CEF)
infected with either strain HPRS-103, the prototype of ALV-J, or field isolates
of ALV-J obtained from broiler breeder flocks in the United States that exhibited
myeloid leukosis. The newly developed PCR detected ALV-J in DNA prepared from CEF
inoculated with ALV-J but not from CEF inoculated with subgroup A, B, C, D, or E.
The PCR also detected ALV-J in DNA prepared from blood, combs, and toes obtained
from chickens experimentally infected with ALV-J and in DNA obtained from
peripheral blood monocytes from naturally infected broiler breeder chickens. The
PCR described here offers a specific and sensitive alternative to conventional
virus isolation tests for ALV-J.
PMID- 9645330
TI - Frequency of isolation of Salmonella from protective foot covers worn in broiler
houses as compared to drag-swab sampling.
AB - In this study we tested the hypothesis that the frequency of Salmonella isolation
from protective foot covers worn in individual broiler production houses would
compare favorably to isolation rates obtained from conventional drag-swab
methods. Salmonella was detected with equal frequency from protective foot covers
and drag-swab assemblies on nine individual broiler farms over three separate
sampling periods. Salmonella was detected in 13 of a total 27 individual
samplings by culturing the protective foot covers, whereas positive detections
occurred in 16 of a total 27 samplings when using the drag-swab method. Of the
total number of houses identified as positive, these frequencies were unaltered
when evaluated against the flock status of each farm at the time of sampling.
Both methods were equally as likely to detect Salmonella when houses were either
vacant (awaiting the placement of the next flock) or occupied (currently housing
chickens of any age). In addition to highlighting the development of a potential
new Salmonella monitoring technique, this study reinforces our current
understanding regarding the importance of stringent biosecurity practices on
poultry farms.
PMID- 9645331
TI - Effect of Poultry Litter Treatment (PLT) on death due to ascites in broilers.
AB - The purposes of this study were to determine the effect of Poultry Litter
Treatment (PLT) on levels of litter moisture, litter nitrogen, atmospheric
ammonia, and death due to ascites. Data were collected from chicks raised in
containment conditions that resembled commercial settings. The ascites death rate
(5.9%) in broiler chicks on PLT-treated litter was significantly (chi 2 = 15.5,
df = 1, P = 0.0001) lower than that (31.5%) in broiler chicks raised on untreated
litter. Likewise, atmospheric ammonia levels in pens that had been treated with
PLT were significantly (P < 0.05) lower than those in pens that received no
treatment. Under the conditions of the present study, litter moisture and litter
nitrogen levels were not different (P > 0.05) among treatments at any sample
interval.
PMID- 9645332
TI - Immunorheophoresis for the diagnosis of infectious bursal disease.
AB - The immunorheophoresis (IR) technique was used for the detection of infectious
bursal disease antigen from bursae collected from field cases and experimentally
infected chickens. When these results were compared with that of the agar gel
immunodiffusion (AGID) test, they showed excellent agreement as determined by
kappa value. However, the time taken for the appearance of the precipitin lines
was reduced from 14-24 hr in the AGID test to 3-5 hr in the IR technique.
PMID- 9645333
TI - Serologic incidence of some diseases in Kansas wild turkeys.
AB - Wild turkeys (Meleagris gallopavo, n = 1164) were tested for Mycoplasma
gallisepticum, Mycoplasma meleagridis, Mycoplasma synoviae, and Salmonella
pullorum from 1990 to 1997. Although 3.3% of the turkeys were suspect for one or
more diseases, only 0.9% were serologically positive for M. gallisepticum. These
11 positives were all from one country in south-central Kansas.
PMID- 9645334
TI - Genetic influence on nitric oxide production during Eimeria tenella infections in
chickens.
AB - Studies were carried out to assess the importance of nitric oxide (NO) production
in vivo in resistance to Eimeria tenella infections through treatment of
resistant SC and susceptible TK strains of chickens with compounds proven to be
effective inhibitors of induced nitric oxide synthase. The SC strain produced
higher levels of plasma NO2- + NO3- in response to primary infection than did the
TK strain. SC chickens were also more responsive in reduction of NO2- + NO3-
levels and increased oocyst output in response to treatments with S
methylisothiourea or NG-methyl-L-arginine (LNMA) during primary infection.
However, the SC strain, regardless of drug treatment, consistently yielded higher
oocyst output during primary infection, indicating it could be susceptible to a
higher parasite burden. On the other hand, the SC strain seemed to develop
immunity more rapidly than the TK strain, in that oocyst output was decreased in
both untreated and LNMA-treated chicks upon challenge infection compared with
that of the TK strain. Oocyst output from both SC and TK strains was further
decreased by LNMA treatment during challenge infection rather than increased,
suggesting minimal involvement of NO production in the immune response to
challenge. These results indicate that NO production during primary E. tenella
infection may be only one of several immune responses and may not be the main
anticoccidial effector.
PMID- 9645335
TI - Eradication of live F strain mycoplasma gallisepticum vaccine using live ts-11 on
a multiage commercial layer farm.
AB - Subsequent to use of a live Mycoplasma gallisepticum (MG) vaccination program,
the F strain of MG had been circulating on a commercial layer farm since 1981. In
1994, the ts-11 strain was introduced on the farm; each new placement flock was
vaccinated by eyedrop with ts-11 for one production cycle, and then all
subsequent placement flocks were left unvaccinated. Birds were monitored by
culture and serology before and after vaccination. MG isolates were characterized
by random amplified polymorphic DNA (RAPD). MG was isolated from ts-11-vaccinated
flocks up to 100 wk of age; all such isolates tested by RAPD were ts-11 type.
After ts-11 vaccination was discontinued, no MG was detected in nonvaccinated
birds. After the last vaccinated flock was marketed, no MG was detected on the
farm. These results indicate a potential use for ts-11 in an MG eradication
program.
PMID- 9645336
TI - Axillary cystadenocarcinoma in a Moluccan cockatoo (Cacatua moluccensis).
AB - An adult Moluccan cockatoo (Cacatua moluccensis) was diagnosed with a
cystadenocarcinoma in the right axillary region that was treated symptomatically
with surgical debulking and periodic drainage. The bird eventually died and a
necropsy was performed. The neoplasm extended through the humerus, and small
neoplastic foci were seen within the ipsilateral lung parenchyma. Rare groupings
of microvilli were observed lining intercellular canalicular lumens on electron
microscopy within the axillary tumor. These findings suggest a respiratory
neoplasm, although the tissue of origin remained undetermined.
PMID- 9645337
TI - Pasteurella multocida infection involving cranial air spaces in White Leghorn
chickens.
AB - Seven 18-wk-old pullets from a commercial layer flock experiencing increased
mortality associated with neurologic and respiratory symptoms were submitted to
the California Veterinary Diagnostic Laboratory System at the Turlock Branch for
necropsy. Clinical signs included depression, torticollis, swollen eyelids,
conjunctivitis, and sinusitis. Meningoencephalitis and suppurative inflammation
of the cranial air spaces were found on histopathology. The brain, sinuses, and
air spaces of the cranium were infected with Pasteurella multocida. Complicating
the condition was Mycoplasma gallisepticum infecting the sinus and paramyxovirus
I affecting the trachea.
PMID- 9645338
TI - Avian paramyxoviruses serotype 3 isolated from captive birds in Israel: clinical
signs, pathology, and antigenic characterization.
AB - Thirteen HA agents were isolated in Israel from captive flamingoes
(Phoenicopterus ruber), Egyptian geese (Alopochen aegyptiacus) belonging to order
Anseriformes, and ibis (Guara rubra) belonging to order Ciconiiformes. The
isolation was done from postmortem materials in three cases of severe respiratory
disease with high mortality. The isolates were examined serologically and
identified as belonging to the serotype 3 of avian paramyxoviruses (APMV-3). The
isolates were more close antigenically to the APMV-3b variety (prototype strain-
APMV-3/Parakeet/Netherlands/449/75) than to the APMV-3a variety (prototype strain
-APMV-3/Turkey/Wisconsin/68). This is the first isolation of APMV-3 from birds
belonging to the orders Anseriformes and Ciconiiformes.
PMID- 9645339
TI - Intravascular cartilaginous emboli in the spinal cord of turkeys.
AB - A flock of 15-wk-old tom turkeys experienced an acute onset of paresis and ataxia
in 75% of the birds after handling. Cartilaginous emboli were found in the spinal
cord vasculature from one of five turkeys at this initial presentation. Most of
the flock recovered within 6 days, but 3% remained paretic. Myelomalacia was
present in three turkeys that failed to recover. Two of these turkeys had
cartilaginous and osseous emboli within the medullary spaces of the vertebral
bodies, internal vertebral venous sinuses, and spinal cord. The third turkey had
vascular and spinal cord necrosis consistent with thrombosis and resultant
ischemia. These changes suggest that turkeys may be susceptible to a syndrome
analogous to fibrocartilaginous embolism of the spinal cord in mammals. The
articular cartilage of the vertebral body endplate may be the source of the
emboli. The turkeys with emboli had articular cartilage defects consisting of
matrix eosinophilia, chondrocyte loss, multicellular cluster formation, cartilage
detachment, and cartilage clefts. Cartilaginous emboli in the spinal cord should
be considered as a potential cause for acute paresis and ataxia, especially in
flocks with preexisting abnormalities of the vertebral articular cartilage
surfaces.
PMID- 9645340
TI - Correlation between methylation status of the p16/CDKN2 gene and the expression
of p16 and Rb proteins in primary non-small cell lung cancers.
AB - In order to clarify the frequency of p16 gene inactivation and its relationship
with Rb expression, immunohistochemical analysis of p16 and Rb proteins was
carried out on 82 paraffin-embedded sections of primary non-small cell lung
cancers (NSCLCs). From immunohistochemical results, abnormal p16 expression was
observed in 66% of NSCLCs, 80% in squamous cell carcinomas and 46% in
adenocarcinomas. An inverse correlation between p16 and Rb expressions was noted.
Moreover, the methylation status of the p16 gene was investigated by the
methylation-specific polymerase chain reaction (MS-PCR) using 29 frozen samples
of NSCLCs. MS-PCR revealed the methylation of the p16 gene in 10(34%)of 29
NSCLCs. All NSCLCs exhibiting methylation exhibited abnormal p16 expression and
were positive for Rb. In NSCLCs, no difference in methylation status was observed
with respect to clinico-pathological characteristics including histological
subtype and tumor stage. Our results demonstrate that abnormality of p16
expression is frequent in primary NSCLCs and methylation of the promoter of the
p16 gene occurs in 34% of primary NSCLCs, which might play a significant role in
the inactivation of the p16 gene.
PMID- 9645341
TI - Clinical significance of circulating CD44 in non-Hodgkin's lymphoma.
AB - Soluble isoforms of various adhesion molecules have recently been observed in the
blood circulation, but the physiological effects of such molecules remain
unsettled. Our earlier results indicate that soluble CD44 can be detected in sera
of healthy individuals and that significantly higher levels of serum CD44 (s
CD44) can be found in lymphoma patients. The serum level of the standard form of
CD44 parallels the clinical treatment response in patients with lymphoma. In the
present study, we have investigated the clinical significance of s-CD44 in non
Hodgkin's lymphoma measured at the time of the diagnosis. S-CD44 was measured
from the sera of 123 patients with non-Hodgkin's lymphoma by dot blotting high
levels of s-CD44 were associated with high serum levels of lactate dehydrogenase
and thymidine kinase, high histological grade of malignancy and poor overall
survival. However, s-CD44 level did not have independent prognostic value in a
multivariate analysis. In conclusion, a high s-CD44 level at the time of
diagnosis was associated with poor survival and several other adverse prognostic
factors. Our previous and present studies taken together suggest that measurement
of s-CD44 is a valuable tool to monitor treatment response in lymphoma patients.
However, it may not be an improved prognostic marker.
PMID- 9645342
TI - Neuronal src and trk a protooncogene expression in neuroblastomas and patient
prognosis.
AB - Neuroblastomas present a wide variety of clinical and biological behaviors, which
are reflected by the heterogeneous expressions of protooncogenes related to the
neuronal differentiation and amplification of the N-myc gene. High expression of
trk A and Ha-ras in neuroblastomas has been shown to be associated with an
excellent patient outcome. We have previously reported that neuron-specific src
mRNA was increased in chemically differentiated neuroblastoma cell lines and in
clinically observed neuroblastomas without N-myc amplification. In the present
study, to clarify both the value of neuronal c-srcN2 expression as a prognostic
indicator and the significance of the coexpression of these protooncogenes, we
examined the expression of 3 alternatively spliced src, trk A and Ha-ras in
neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain
reaction (PCR). The results indicate that protooncogene expression in
neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc
gene was amplified exclusively in tumors with low levels of trk A. Low expression
of c-srcN2 and trk A might thus characterize different aggressive phenotypes due
to different signal transduction pathways of neural differentiation in
neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR
should provide information about the biological phenotype of a neuroblastoma
within a short period of time after obtaining tumor material.
PMID- 9645343
TI - Differential expression of key enzymes of energy metabolism in preneoplastic and
neoplastic rat liver lesions induced by N-nitrosomorpholine and
dehydroepiandrosterone.
AB - Preneoplastic liver foci and neoplasms of different morphological phenotypes were
induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7
weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the
diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred
mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly
observed in rats treated with DHEA alone or in combination with NNM. The 2 types
of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic
lineage and the amphophilic lineage, which are characterized by distinct patterns
of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of
glucose metabolizing pathways were modified (increase in glucose-6-phosphate
dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly
demonstrated alterations in mitochondrial enzymes (increase in cytochrome c
oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to
a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and
acyl-CoA oxidase). The alterations in enzyme expression reflect an
insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms
resulting from APF show a more differentiated phenotype than those arising from
GSF. We suggest that the different and in many aspects opposite effects of the 2
carcinogens on key enzymes of distinct pathways of energy metabolism modulate the
process of neoplastic liver cell transformation and result in phenotypically
different preneoplasias and neoplasias reflecting different cellular lineages.
PMID- 9645344
TI - Tissue polypeptide specific antigen in the follow-up of ovarian and cervical
cancer patients.
AB - This retrospective study includes 425 serological examinations of 40 patients
with epithelial ovarian cancer and 356 serological examinations of 33 patients
with squamous cell cervical cancer. The serum levels of the tumor markers tissue
polypeptide specific antigen (TPS), carbohydrate antigen 125 (CA 125) and
squamous cell carcinoma antigen (SCC) were determined. Cutoff values of 93 U/l
for TPS, 3 microg/l for SCC and 37 U/ml for CA 125 were selected according to the
95th percentile of serum concentrations measured in healthy control patients. For
ovarian cancer sensitivity, specificity, positive predictive value (PPV) and
negative predictive value (NPV) of TPS were 67%, 84%, 59% and 90%, respectively.
In 27 patients with recurrent ovarian cancer, CA 125 and TPS showed lead time
effects in 8 and 11 cases, respectively. The combination of CA 125 and TPS
provided lead time in 14 cases of recurrent disease with a time range from I to
23 months (median 3.9 months). In cervical cancer, TPS showed a sensitivity,
specificity, PPV and NPV of 64%, 90%, 85% and 68%, respectively. In 16 patients
with recurrent cervical cancer, SCC and TPS showed lead time effects in 7 and 8
cases, respectively. The combination of SCC and TPS provided lead time effects in
12 cases with a time range from 0.5 to 6 months (median 3.5 months). Our data
indicate that TPS is a valuable tool in the follow-up of patients with ovarian or
cervical cancer. However, TPS does not appear to be adequate to replace tumor
markers CA 125 and SCC.
PMID- 9645345
TI - Expression of the smooth muscle calponin gene in human osteosarcoma and its
possible association with prognosis.
AB - The basic calponin gene is a smooth muscle differentiation-specific gene that
encodes an actin-binding protein involved in the regulation of smooth muscle
contractility. We studied the expression of the calponin gene in 8 human
osteosarcoma cell lines and 17 primary human osteosarcoma tissues by RT-PCR
analysis. We also analyzed mRNA expression of smooth muscle-specific genes
including SM22alpha, caldesmon and alpha-actin, and for neutral and acidic
calponin isoforms. The genes were expressed at various levels by osteosarcoma
cell lines and tissues of diverse histological subtypes. The basic calponin
protein of an expected size was detected in osteosarcoma cell lines by immunoblot
analysis and was localized by immunohistochemistry in the cytoplasm of the tumor
cells in osteosarcoma tissues. Survival was found to be significantly increased
in patients whose tumors exhibited basic calponin expression, compared with those
with no expression. Alterations in the expression of other markers examined were
not correlated with prognosis. Our results suggest that the basic calponin gene
product may be a novel prognostic variable in patients with osteosarcoma.
PMID- 9645346
TI - Expression of hyaluronan in normal and dysplastic bronchial epithelium and in
squamous cell carcinoma of the lung.
AB - A series of 85 lung/bronchial tissue samples from 76 patients consisting of
normal, metaplastic and dysplastic epithelium and different types of lung
carcinomas were analyzed for the distribution of hyaluronan (HA), using a
biotinylated hyaluronan binding complex as an HA-specific probe. The normal
pseudo-stratified columnar bronchial epithelium was either negative for HA or
displayed a weak staining around the basal cells. The epithelia of serous and
mucous bronchial glands were HA negative whereas the submucosal connective tissue
was strongly positive. In metaplastic, dysplastic and carcinoma in situ lesions
the whole epithelium from basal to uppermost cells expressed HA on plasma
membranes. Epithelial HA was also found in squamous cell carcinomas, but not in
adenocarcinomas, carcinoid tumors or small cell carcinomas of the lung. Whereas
epithelial HA was present in all lesions of the squamous cell type, the staining
intensity displayed great local variability in 50% of the cases with severe
dysplasia, carcinoma in situ and squamous cell carcinomas. In squamous cell
carcinomas, such an irregular staining pattern was significantly associated with
poor differentiation. Our results indicate that the expression of HA in different
bronchial lesions and lung tumors is restricted to those showing squamous cell
differentiation, being absent from other types of lung carcinomas. The increase
of HA depleted areas in poorly differentiated squamous cell carcinomas emphasizes
the important role of HA in tumor differentiation. HA on carcinoma cell surface
may influence tumor growth and metastatic behavior.
PMID- 9645347
TI - Increased expression of CD44v6 mRNA significantly correlates with distant
metastasis and poor prognosis in gastric cancer.
AB - Expression of CD44 and its variants is associated with clinically aggressive
behavior of some human cancers. The present study was undertaken to determine the
expression level of these CD44 mRNAs in relation to the clinicopathologic
features and prognosis of gastric cancer. Using reverse transcription polymerase
chain reaction followed by Southern blotting, we examined the expression of the
standard and variant (v6 and v9) forms of CD44 mRNA in 73 cases of gastric
cancer. We determined the ratio of mRNA expression in cancer tissue to normal
tissue (T/N ratio) and evaluated the correlations of the ratio with clinico
pathologic features, tumor progression and prognosis. The expression level of the
standard form of CD44 (CD44s) mRNA correlated with peritoneal dissemination only,
and that of CD44v9 mRNA did not significantly correlate with any
clinicopathologic factor. The expression level of CD44v6 mRNA was significantly
higher in patients with lymph node metastasis and liver metastasis. In 48
curatively resected patients, the expression level of CD44v6 mRNA correlated with
the site of recurrence. Furthermore, there was a significant survival advantage
in patients with low expression of CD44v6 mRNA compared with those with high
expression. The level of CD44v6 mRNA expression may be a potential prognostic
indicator and may be useful as a predictor for distant metastasis and recurrence
in patients with gastric cancer.
PMID- 9645348
TI - Clinical relevance of p53 and bcl-2 protein over-expression in laryngeal squamous
cell carcinoma.
AB - We investigated immunohistochemically the clinical relevance of the over
expression of the apoptosis-regulating proteins p53 and bcl-2 in a homogeneous
series of 149 laryngeal squamous-cell carcinomas. p53 was over-expressed in 75
cases and bcl-2 in 39 cases. p53 and bcl-2 co-expression was found in 21 cases.
p53 and bcl-2 immunoreactivity was significantly associated with poor
histological differentiation and lymph-node metastases. Moreover, a significant
statistical correlation was found between bcl-2 expression, supraglottic tumor
site and advanced disease stage. p53/bcl-2 co-expression was significantly
associated with poor differentiation, tumor extension, the presence of lymph-node
metastases and advanced clinical stage. Univariate analysis showed that a lower
probability of survival was significantly associated with supraglottic site,
tumor extension, advanced clinical stage and p53/bcl-2 co-expression, but not
with p53 or bcl-2 considered separately. In multivariate analysis, only tumor
extension and supraglottic site retained their prognostic value. Our data suggest
that clinical staging remains the most reliable predictive indicator of survival
in patients with laryngeal carcinoma.
PMID- 9645349
TI - Prognostic value of loss of heterozygosity and KRAS2 mutations in lung
adenocarcinoma.
AB - The prognostic values of loss of heterozygosity (LOH) at loci frequently involved
in non-small cell lung cancer and of KRAS2 gene mutations were studied in lung
adenocarcinoma patients. LOHs were relatively common, ranging from 24% at
chromosome 10p to 55% at chromosome 17p13. KRAS2 mutations at codon 12 were
present in 26% of cases, were more common in male than in female patients and
were associated with a smoking habit. No association between LOH at any site and
clinical stage or survival rate was found. On the other hand, we observed a trend
between the presence of any type of KRAS2 mutations and poor survival. Analysis
of specific KRAS2 mutations showed a strong effect of Asp (GAT) and Val (GTT)
mutations, resulting in a very poor survival compared with wild type group,
whereas the most common mutation (Cys, TGT) was not associated with prognosis.
Our results indicate the importance of specific activating mutations of the KRAS2
gene as genetic markers of clinical outcome for patients with lung
adenocarcinoma.
PMID- 9645350
TI - Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia.
AB - In childhood acute lymphoblastic leukaemia there are large interpatient
variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the
molecular basis for this variation is unknown. Point-mutations in bax have been
reported in cell lines derived from haematological malignancies. Frameshift
mutations, which result in reduced Bax levels, have also been found in colon
cancer of the microsatellite mutator phenotype. Bcl-2 overexpression, or gain of
function mutations in the open reading frame (ORF) or in the translational
repressor, the upstream ORF(uORF) of bcl-2, might also be important in
deregulating its function or expression. We have therefore analyzed 21 bone
marrow aspirates from untreated childhood acute lymphoblastic leukaemia and 2
from myeloid leukaemia for mutations in box and bcl-2. DNA sequence analysis of
the ORFs of bax and bcl-2 and of the uORF of bcl-2 revealed no mutations, despite
the large range in expression levels. Thus, mutations within the (u)ORFs of bax
and bcl-2 that (in)activate or deregulate Bax and Bcl-2 are infrequent in primary
childhood acute leukaemia and do not play a major role in regulation of the
encoded proteins in this disease.
PMID- 9645351
TI - Impact of menopausal hormone-replacement therapy on clinical and laboratory
characteristics of breast cancer.
AB - Hormone-replacement therapy (HRT) is widely used by post-menopausal women.
Although this treatment may slightly increase the incidence of breast cancer,
more and more cases are diagnosed while women are taking HRT. The purpose of this
study was to ascertain the influence of HRT on prognostic factors and outcome of
breast cancer. Data on all breast-cancer patients, including precise information
on HRT, was prospectively and systematically recorded in a data base. From 1985
to 1995, 1379 post-menopausal women fulfilled the eligibility criteria for this
study. All were treated by us (P.B. and L.P.) in our ward of a large public
hospital of Marseilles, France. The clinical features, laboratory findings and
survival rates in 142 HRT users who developed breast cancer while being treated
were compared with those of 284 matched never user breast-cancer patients.
Patients who developed breast cancer during HRT had fewer locally advanced
cancers and smaller and better-differentiated cancers. Lymph-node involvement was
significantly less frequent in the user group than in the non-user group (non
significant). Estradiol receptivity was both qualitatively and quantitatively
lower in users. There was no significant difference with regard to recurrence and
metastasis-free survival and overall survival. We conclude that HRT does not
affect the prognosis of breast cancer. Regular surveillance during HRT allows
early detection of smaller lesions. The higher number of well-differentiated
cancers and the distribution of hormone receptivity may reflect interaction
between neoplastic tissue and exogenous hormones.
PMID- 9645352
TI - Flow cytometric investigation of immune-response-related surface molecules on
human colorectal cancers.
AB - Our purpose was to clarify whether human colorectal cancer cells are equipped to
present tumour-associated-antigens to the immune system, and whether this ability
correlates with lymphoid infiltration, the Dukes' stage and Jass classification.
Enzymatically dissociated tumour cells from 70 different colorectal cancers were
monitored by multiparameter flow cytometry. Gating on EP4+ cells, the expression
of the surface molecules HLA class I, HLA class II, CD80 (B7-1), CD54 (ICAM-I)
and CD58 (LFA-3) was evaluated. In 60 of 70 tumours, all tumour cells expressed
HLA class I, in 10 tumours 15-96% of the tumour cells expressed HLA class I. In 1
tumour, all tumour cells expressed HLA class II, in 67 tumours some expressed HLA
class II, in 2 tumours none expressed HLA class II. Expression of CD58 was
heterogeneous, and there was no or only sparse expression of CD80 and CD54.
Expression of the HLA class I molecules, but not the class II, was correlated
with lymphoid infiltration and the Jass classification. Expression of these
surface molecules was not correlated with the Dukes' stage. The tumour cells were
generally equipped to present antigens to the effector arm of the immune system
since HLA class I is expressed, but the tumour cells were not optimal in
stimulating an immune response, since HLA class II and CD58 were only marginally
expressed and CD80 and CD54 were absent.
PMID- 9645353
TI - Detection of colorectal cancer cells in peripheral blood by reverse-transcriptase
polymerase chain reaction for cytokeratin 20.
AB - The staging of colorectal cancer currently depends on pathological examination of
the surgical specimen and regional lymph nodes, accompanied by imaging tests such
as computed tomography (CT) scanning. However, alternative molecular methods to
detect circulating tumour cells in blood or bone marrow may provide additional
information about the extent of disease and prognosis. We have previously
reported the development of a reverse-transcriptase polymerase chain reaction (RT
PCR) for cytokeratin 20 (CK 20) mRNA to detect circulating epithelial tumour
cells. In this study, we report on the application of this method for detecting
circulating tumour cells in patients with colorectal cancer. Using this method,
CK 20 mRNA was detected in 8/8 human colorectal cancer cell lines, in 8/9
biopsies from primary colorectal tumours and in 9/10 biopsies of liver metastasis
in patients with metastatic colorectal cancer, suggesting that CK 20 may be a
useful target for the detection of circulating tumour cells in this patient
group. In spiking experiments, 10 cells were consistently identified in 2 ml of
whole blood (1 x 10(6)-1 x 10(7) mononuclear cells). In 12/25 (48%) peripheral
blood samples from patients with known metastatic colorectal cancer, CK 20 mRNA
was detected. However, there was no correlation between the detection of CK 20
mRNA in the peripheral blood and disease progression and survival in this group
of patients. CK 20 mRNA was detected in 1/12 normal blood samples, which raises
questions about the absolute specificity of CK 20 expression.
PMID- 9645354
TI - Clinical implications of cyclins, cyclin-dependent kinases, RB and E2F1 in
squamous-cell lung carcinoma.
AB - In the search for new risk factors at the molecular and cellular levels, clinical
data [lymph-node involvement(LN)and stage] were used and 104 squamous-cell lung
carcinomas were analyzed by immuno-histochemistry for expression of cyclin D1,
cyclin A, cdk2, cdk4, RB, and E2F1. The results of the univariate analysis of all
8 factors showed that cyclin A and cdk2 gave the best prognostic information,
while no prognostic value could be found associated with cyclin D1, cdk4, RB and
E2F1. The subsequent multivariate analysis of all possible combinations of the
important factors showed that the pairs LN/cyclin A, LN/cdk2 and cyclin A/cdk2,
and the triplet LN/cyclin A/cdk2 yielded the best prognostic information. It was
essentially better than the information given by a single factor.
PMID- 9645355
TI - Chimeric CD4/CD44 molecules associate with CD44 via the transmembrane region and
reduce hyaluronan binding in T cell lines.
AB - Cells of the immune system tightly regulate the binding ability of cell adhesion
molecules. The binding of the extracellular matrix component hyaluronan to CD44
is no exception, yet the mechanisms that regulate its binding are poorly
understood. In this study a chimeric CD4/CD44 molecule, containing the
extracellular domain of CD4 and the transmembrane and cytoplasmic domains of
CD44, was expressed in two CD44+ mouse T lymphoma cell lines, BW5147 and T28.
This resulted in the reduced ability of endogenous CD44 to constitutively bind
hyaluronan. Immunoprecipitation of the chimeric protein in 1 % Brij-96 indicated
an association between the chimera and endogenous CD44. Using various chimeric
CD4/CD44 molecules, the transmembrane region of CD44 was found to mediate this
association. In addition, the association of chimeric CD4/CD44 molecules with
endogenous CD44 correlated with reduced hyaluronan binding. Thus, the
transmembrane region of CD44 is required for the association with CD44 molecules
in the cell membrane and we propose that the self-association of CD44 molecules
occurs on the T cell surface to promote hyaluronan binding. Cellular events
altering the interactions of the transmembrane region of CD44 thus have the
potential to regulate the hyaluronan binding ability of CD44.
PMID- 9645356
TI - Two models of murine B lymphopoiesis: a correlation.
AB - During B cell genesis in mouse bone marrow (BM), precursor B cells pass through a
series of developmental stages that have been defined by changes in expression of
various marker molecules. The use of dissimilar phenotypic criteria in different
laboratories, however, has led to the formulation of disparate models of B
lymphopoiesis not fully reconciled with one another. We have directly compared
two such models, one based on expression of intracellular mu heavy chain of IgM
(c mu) and terminal deoxynucleotidyl transferase (TdT), the other monitoring cell
surface leukosialin (CD43), heat-stable antigen (HSA; CD24) and the ectopeptidase
BP-1. Each model uses cell surface B220 glycoprotein (CD45RA) to denote the B
cell lineage. We have examined the cellular composition of four sorted BM
fractions by immunofluorescent labeling of CD43, HSA and BP-1, using
immunofluorescence microscopy of cytocentrifuged fractions to quantitate
precursor B cell populations expressing either c mu or TdT. The results reveal a
range of B cell differentiation stages within individual sorted BM fractions,
providing a cross-reference between these two analytical methods and contributing
to a unified model of B cell development in mouse BM.
PMID- 9645357
TI - Failure of P strain mice to respond to vaccination against schistosomiasis
correlates with impaired production of IL-12 and up-regulation of Th2 cytokines
that inhibit macrophage activation.
AB - In contrast to most inbred strains, P mice fail to develop significant resistance
to Schistosoma mansoni infection as a result of vaccination with either radiation
attenuated cercariae or schistosome antigens plus Bacillus Calmette Guerin, and
this failure correlates with defects in macrophage larvicidal activity.
Supernatant fluids from antigen-treated in vitro cultures of splenocytes from
vaccinated P mice demonstrate less macrophage stimulatory activity than do
supernatants from cells of vaccine-responsive strains such as C57BL/6. This is
not due either to diminished production of the macrophage-activating cytokine IFN
gamma by P mice, or to a lesser responsiveness of macrophages from P mice to
activation by IFN-gamma. Rather, P splenocytes produce two-to threefold higher
amounts of IL-4 and IL-10, cytokines which down-regulate the cytotoxic potential
of IFN-gamma-treated macrophages. Thus, the macrophage-activating potential of
cytokine preparations from vaccinated P mice can be completely recovered by in
vitro treatment with antibodies to IL-4 or IL-10. Moreover, lower levels of IL
12, a cytokine involved in promoting development of Th1 responses, are produced
by splenocytes from P mice as compared to C57BL/6 counterparts. These studies
indicate that a genetic predisposition toward an impaired production of IL-12 and
an increased production of down-regulatory Th2 cytokines correlate with low
response to vaccination against S. mansoni.
PMID- 9645358
TI - Expression of matrix metalloproteinases by human plasma cells and B lymphocytes.
AB - Matrix metalloproteinases (MMP) are proteolytic enzymes that play a key role in
tissue remodelling during physiological and pathological processes, by initiating
the degradation of extracellular matrix. MMP overexpression can lead to tissue
destruction which is characteristic of chronic inflammatory diseases such as
rheumatoid arthritis and scleritis. Plasma cells are often abundant at such sites
of chronic inflammation. In the present study we investigated whether plasma
cells could contribute to matrix degradation by their expression of MMP In situ
hybridization and immunohistochemical analyses on diseased synovial and scleral
tissue demonstrated the expression of stromelysin-1 (MMP-3) and gelatinase B (MMP
9), but little or no tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)
mRNA, by IgG-positive plasma cells. Northern blot analysis of RNA extracted from
a human plasma cell line (ARH-77), Epstein-Barr virus-transformed B cells, and
purified peripheral blood B cells, demonstrated expression of stromelysin mRNA.
TIMP-1 mRNA was only detected by the more sensitive reverse transcription PCR
method in these cell types. Plasma cells and B lymphocytes cultured in the
presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin and casein
zymography on conditioned media (CM) derived from cytokine treated plasma cells
revealed the induction of secreted gelatinase and stromelysin activity. Western
blotting confirmed the presence of stromelysin-1 and TIMP-1 proteins in plasma
cell CM. These data suggest that plasma cells are not only capable of modulating
an inflammatory response by antibody and cytokine production, but also by their
ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells
may play a critical role in tissue destructive diseases such as rheumatoid
synovitis and scleritis.
PMID- 9645359
TI - Expression of selectin-binding epitopes and cytokines by CD4+ T cells
repopulating scid mice with colitis.
AB - Recruitment into the gut of CD4+ T cells and their activation in the colonic
lamina propria (LP) are key events in the development of colitis in scid mice
reconstituted with CD4+ T cells from immunocompetent, congenic donor mice. This
study investigated the expression of cytokines and selectin-binding epitopes by
CD4+ T cells repopulating different tissues of the adoptive scid host. Cells from
the inflamed colonic LP of transplanted scid mice produced high amounts of IL-12,
IFN-gamma and TNF-alpha but only low amounts IL-4 and IL-10. Intracellular
cytokine staining confirmed the presence of large numbers of IFN-gamma- and TNF
alpha-producing effector CD4+ T cells in the colonic LP of scid mice with colitis
but also in non-inflamed tissues [spleen (S), peritoneal cavity (PC) and
mesenteric lymph nodes (mLN)] of the adoptive host. Cells from these tissues
furthermore produced large amounts of IL-12. Ligands for endothelial selectins
are involved in recruiting T cells into inflamed tissues. We have analyzed the
expression of selectin-binding epitopes on CD4+ T cells repopulating different
tissues of the adoptive scid host. We found that a large fraction of CD4+ T cells
from inflamed colonic LP and from non-inflamed PC, mLN and S expressed high
levels of P- and E-selectin-binding epitopes (P-Lhi) in transplanted scid mice,
but not in congenic, immunocompetent control mice. Although P-Lhi CD4+ T cells
were enriched in IFN-gamma-producing subsets from most (but not all) tissues, we
also found large numbers of in vivo generated P-Llo CD4+ T cells producing pro
inflammatory cytokines. This was in contrast to in vitro generated Th1 CD4+ T
blasts that were almost exclusively P-Lhi. In this mouse model, production of Th1
type pro-inflammatory cytokines and expression of surface epitopes binding
endothelial selectins are hence strikingly up-regulated in CD4+ T cells residing
in inflamed and non-inflamed tissues during the development of colitis.
PMID- 9645360
TI - Mycobacterium tuberculosis exploits the CD95/CD95 ligand system of gammadelta T
cells to cause apoptosis.
AB - Vgamma9/Vdelta2+ T cells specifically recognize Mycobacterium tuberculosis in
vitro and are precociously recruited in early mycobacterial lesions. Even if
gammadelta T cells are only fortuitously detected in granulomas or
bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in
shaping the mature alphabeta T cell response against M. tuberculosis is
substantiated. Here we provide a molecular explanation for this paradox: the
engagement of the gammadelta TCR by mycobacterial antigens induced the expression
of CD95 ligand (CD95L) by chronically activated CD95+/CD95L- gammadelta T
lymphocytes. The receptor was functional, as CD95/CD95L interaction triggered the
bystander death of CD95+ cells by apoptosis. Cell death was abolished by CD95
blocking antibodies. The transient accumulation at the site of infection of
CD95L+ gammadelta lymphocytes, capable of interacting with CD95+ leukocytes
attracted by the response towards the pathogen, may determine the characteristics
of the ensuing granulomatous disease.
PMID- 9645361
TI - Attenuated Listeria monocytogenes carrier strains can deliver an HIV-1 gp120 T
helper epitope to MHC class II-restricted human CD4+ T cells.
AB - Listeria monocytogenes is a facultative intracellular pathogen which, following
uptake by macrophages, escapes from the phagosome and replicates in the
cytoplasm. This property has been exploited using recombinant L. monocytogenes as
a carrier for the intracytoplasmic expression of antigens when MHC class I
restricted cytotoxic T lymphocyte responses are required. Much less is known of
the ability of these bacteria to trigger MHC class II-restricted responses. Here,
we demonstrate that after ingestion of L. monocytogenes expressing a T helper
epitope from the gp120 envelope glycoprotein of HIV, human adherent macrophages
and dendritic cells can process and present the epitope to a specific CD4+ T cell
line in the context of MHC class II molecules. No significant differences were
observed when the attenuated strains were trapped in the phagolysosome or
impaired in the capacity to spread intracellularly or from cell to cell. Similar
results were obtained using carrier proteins that were either secreted,
associated with the bacterial surface, or restricted to the bacterial cytoplasm.
A dominant expression of the TCR Vbeta 22 gene subfamily was observed in specific
T cell lines generated after stimulation with the recombinant strains or with
soluble gp120. Our data show that in this in vitro system L. monocytogenes can
efficiently deliver antigens to the MHC class II pathway, in addition to the well
established MHC class I pathway. The eukaryotic cell compartment in which the
antigen is synthesized, and the mode of display seem to play a minor role in the
overall efficiency of epitope processing and presentation.
PMID- 9645362
TI - Alpha-1 antitrypsin up-regulates human B cell differentiation selectively into
IgE- and IgG4- secreting cells.
AB - Numerous allergens have proteolytic activities. It has been speculated that this
property may contribute to their allergenicity. Therefore, we have evaluated the
effect of different physiological protease inhibitors (PI) on the regulation of
human IgE synthesis. Unexpectedly, the serine PI, alpha-1 antitrypsin, also
called alpha-1 protease inhibitor (alpha1PI), induced a potent and selective dose
dependent increase of IgE and IgG4 production by human tonsillar B cells
stimulated with the IgE and IgG4 switch factors, IL-4 and anti-CD40 mAb. The
other serine PI tested were inefficient. Furthermore, this effect of alpha1PI was
accompanied by an increase in (1) germ-line and mature sigma mRNA transcription,
(2) proliferation and (3) membrane CD23 and CD21 expression, while the expression
of other molecules involved in the regulation of IgE synthesis was unchanged.
Since CD23-CD21 pairing plays a crucial role in the up-regulation of IgE
synthesis, we have tested whether blocking this interaction affected alpha1PI
increased IgE production. The neutralizing anti-CD23 mAb, Mab 25, partly reversed
the IgE increase caused by alpha1PI. Moreover, alpha1PI potentiation of IgE
synthesis was prevented by elastase, a natural substrate of alpha1PI, thereby
suggesting that alpha1PI may inhibit endogenous B cell enzyme(s) involved in the
down-regulation of IgE synthesis. Alpha1PI also potentiated IgE and IgG4
production by IL-4-stimulated peripheral blood mononuclear cells but was not a
switch factor for IgE and IgG4 as it was unable to replace IL-4 or anti-CD40 mAb
in inducing IgE and IgG4 production. In conclusion, this study shows that
alpha1PI acts as a potent co-stimulus for IgE and IgG4 synthesis and suggests
that the equilibrium between protease/ protease inhibitor participates in the
control of human IgE and IgG4 synthesis.
PMID- 9645363
TI - Normal immunoglobulin G protects against experimental allergic encephalomyelitis
by inducing transferable T cell unresponsiveness to myelin basic protein.
AB - Normal human IgG for intravenous use (IVIg), administered intraperitoneally,
protected Lewis rats against experimental allergic encephalomyelitis (EAE)
induced by immunization with myelin basic protein (MBP). We demonstrate that
protection was associated with an acquired unresponsiveness of lymphocytes to MBP
and a decreased ability of the cells to produce IL-2, IFN-gamma and TNF-alpha
and, to a lesser degree, IL-4 and IL-10, in the presence of the antigen. Lymph
node (LN) cells of protected rats failed to passively transfer EAE to naive
syngeneic animals. Our observations indicate that, rather than inducing selective
immune deviation, IVIg induces preferential MBP unresponsiveness of Th1 cells.
Whereas LN and splenic cells of IVIg-treated rats did not proliferate nor secrete
IL-2 in the presence of the antigen, proliferation was restored by adding
exogeneous recombinant IL-2. In contrast, LN cells of IVIg-treated rats
proliferated normally and produced IL-2 in the presence of concanavalin A,
indicating the selectivity for MBP of the anergy induced by IVIg when given at
the time of immunization with the antigen. Treatment with IVIg also allowed a
resistance to the secondary induction of EAE, indicating that IVIg protects from
EAE but does not interfere with the processes that eventually lead to resistance
to re-challenge. These data document the immunomodulatory effects of IVIg in T
cell-dependent experimental autoimmune disease and further suggest a role for
normal Ig in the selection of functional T cell repertoires.
PMID- 9645364
TI - Immunological memory after somatic transgene immunization is positively affected
by priming with GM-CSF and does not require bone marrow-derived dendritic cells.
AB - Inoculation of plasmid DNA is a promising vaccination approach but optimal
regimes and ways to enhance immunogenicity remain to be established. Among
natural immunological adjuvants, granulocyte-macrophage colony-stimulating factor
(GM-CSF) was shown to increase the potency of immunization against tumor cells
and protein antigens. Here we studied the effect of GM-CSF on memory responses
against a 12-mer B cell epitope in mice primed with a single DNA inoculation. The
results show that GM-CSF given at priming as a DNA/GM-CSF chimeric vaccine
enhances the magnitude of the anamnestic response irrespective of the form of
antigen used subsequently in the booster immunization. Using mice lacking bone
marrow-derived dendritic cells we also determined that the enhancing effect is
not strictly dependent on these cells. These results expand our understanding of
the activity of GM-CSF in vivo as a modulator of the immune response including
immunological memory.
PMID- 9645365
TI - Identification of a human member of the Ly-49 multigene family.
AB - Three classes of multigene family-encoded receptors enable NK cells to
discriminate between polymorphic MHC class I molecules: Ly-49 homodimers,
CD94/NKG2 heterodimers and the killer cell inhibitory receptors (KIR). Of these,
CD94/NKG2 has been characterized in both rodents and humans. In contrast, Ly-49
family members have hitherto been found only in rodents, and KIR molecules only
in the human. In this report, we describe a human cDNA, termed Ly-49L, that
constitutes the first human member of the Ly-49 multi-gene family. Compared with
rodent Ly-49 molecules, the Ly-49L sequence contains a premature stop codon and
predicts a truncated protein that lacks the distal part of a C-terminal lectin
domain. Evidence is presented that the premature stop codon results from
incomplete excision of the intron between the first two lectin domain exons.
Splice variants predicting a full-size Ly-49L protein were not detected. As
demonstrated by Northern blot analysis, Ly-49L was transcribed by IL-2-activated
NK cells, but not by freshly isolated B or T cells. PCR screening of a 22-clone
yeast artificial chromosome contig localized the LY49L locus to the human NK gene
complex on chromosome 12p12-p13. Southern blot analysis of genomic DNA showed a
simple pattern with a full-length Ly-49L probe at low stringency hybridization
conditions, suggesting that Ly-49L may be the only human member of the Ly-49
multigene family.
PMID- 9645366
TI - Functional heterogeneity of Thy-1 membrane microdomains in rat basophilic
leukemia cells.
AB - Antibody-mediated cross-linking of Thy-1 glycoprotein on the surface of rat mast
cells and rat basophilic leukemia (RBL) cells initiates biochemical events which
culminate in secretion of allergy mediators. Thy-1, like some other
glycosylphosphatidylinositol (GPI)-anchored proteins, forms detergent-insoluble
complexes containing protein tyrosine kinases (PTK) and some other molecules
which are implicated in the signaling pathway. On the surface of a rat mast cell
there are more than 10(6) Thy-1 molecules; however, it is not known which
fraction of them is involved in transmembrane signaling, and what exactly is the
heterogeneity of Thy-1 complexes. Using sucrose density gradient
ultracentrifugation of detergent-lysed RBL cells we found that the density of Thy
1 complexes depended on the detergent used and the lysis conditions employed.
Sepharose 4B gel chromatography fractionation followed by density gradient
ultracentrifugation revealed both size and density heterogeneity of Thy-1 and Lyn
PTK complexes. Cross-linking of surface Thy-1 caused significant changes in the
density of these complexes, and an increase in Lyn kinase activity in low/medium
density fractions. Thy-1 in low-density fractions was relatively resistant to
cleavage with phosphatidylinositol-specific phospholipase C (PI-PLC).
Interestingly, removal of only a small fraction of surface Thy-1 by PI-PLC
abolished the cell activation as determined by tyrosine phosphorylation of
certain proteins. When Triton X-100 lysates were fractionated at 12000 x g, about
50 % of Thy-1 remained associated with the nuclear/cytoskeleton pellet; this
fraction of Thy-1 exhibited an increased sensitivity to PI-PLC. Confocal laser
scanning microscopy on fixed cells revealed that the total Thy-1 was relatively
homogeneously distributed over the plasma membrane, whereas the PI-PLC-resistant
Thy-1 was found mostly in small clusters. The combined data suggest that
specialized membrane microdomains enriched in Thy-1 with increased sensitivity to
PI-PLC are directly involved in coupling Thy-1 aggregation to transmembrane
signaling.
PMID- 9645367
TI - Distinct roles of the interleukin-7 receptor alpha chain in fetal and adult
thymocyte development revealed by analysis of interleukin-7 receptor alpha
deficient mice.
AB - Mouse mutants lacking expression of the IL-7 receptor (IL-7R) alpha chain are
defective in thymopoiesis. The adult thymus has multiple defects, including
reduced cell numbers and proportions of the more mature thymocyte subsets, a
complete absence of CD25+ cells and a reduced level of RAG1 and RAG2 expression.
We show here that, in contrast to the profound developmental arrest observed in
the adult thymus, fetal thymocytes from IL-7Ralpha-/- mice have normal
proportions of all of the major thymocyte subpopulations, including CD25+
thymocytes and the most mature single-positive subsets. Moreover, normal levels
of RAG1 and RAG2 were observed. Total thymocyte numbers, however, remained
reduced. These data suggest that the IL-7Ralpha chain is a key regulator of both
survival and proliferation during thymocyte development but that it is not
essential for the production of T cells during fetal thymopoiesis.
PMID- 9645368
TI - The antigen presentation pathway in medullary thymic epithelial cells, but not
that in cortical thymic epithelial cells, conforms to the endocytic pathway.
AB - Murine medullary thymic epithelial cells (mTEC), but not cortical thymic
epithelial cells (cTEC), are able to present a soluble antigen, ovalbumin, to
helper T cells (Mizuochi, T. et al., J. Exp. Med. 1992. 175: 1601-1605). This
functional difference between the mTEC and the cTEC is particularly important
when we consider the thymic selection of the T cell repertoire. In the previous
report, we proposed that mTEC and cTEC utilize two distinct antigen
processing/presenting pathways (Kasai, M. et al., Eur. J. Immunol. 1996. 26: 2101
2107). In this report, we further confirmed this difference by analyzing (a)
localization of MHC class II, H2-DM, and invariant chain (li) molecules, (b) the
biochemical nature of MHC class II molecules, (c) the sensitivity of MHC class II
alphabeta heterodimer formation to concanamycin A, a vacuolar H+-ATPase
inhibitor, and (d) the subcellular distribution of MHC class II, H2-DM, and li
molecules, in both TEC. Our results demonstrated that, in the mTEC, MHC class II,
H2-DM and li molecules gain access to the endocytic pathway, where the luminal
condition is acidic and thus li molecules are efficiently degraded and H2-DM
molecules function well. In the cTEC, however, such molecules seemed to gain
access to an alternative transport pathway, e.g. a secretory pathway, where the
luminal condition is not fully acidic. These two distinct antigen processing
pathways may account for the functional difference between mTEC and cTEC.
PMID- 9645369
TI - Involvement of phosphoinositide 3-kinase and Rac in membrane ruffling induced by
IL-2 in T cells.
AB - IL-2 is known to play a critical role in regulating T lymphocyte proliferation.
We show here that IL-2 also provokes an instantaneous and sustained membrane
ruffling in cloned human or murine T cells as well as in lectin-activated
peripheral blood lymphocytes. In the IL-2-induced lamellipodia, tubulin is
depolymerized whereas actin is strongly polymerized, forming caps. IL-2-induced
membrane ruffling is protein kinase C (PKC) independent, as judged by the absence
of effects of bisindolylmaleimide, an efficient inhibitor of all PKC isoforms.
The formation of lamellipodia by IL-2 is blocked by wortmannin and LY294002, two
inhibitors of phosphoinositide 3-kinase (PI3-kinase). Moreover, expression in
murine T cells of an inactive form of P13-kinase inhibits IL-2-induced membrane
ruffling, whereas expression of a constitutively active p110 increases the basal
membrane ruffling. Rac is also involved in IL-2-induced membrane ruffling since
an inactive form of Rac (N17rac) blocks the IL-2-induced lamellipodia, whereas
the constitutive form of Rac (Val12rac) can also lead to membrane ruffling. In
the signaling cascade, Rac is downstream of PI3-kinase since constitutive
membrane ruffling in Val12rac cells is insensitive to wortmannin. Thus, through a
signaling cascade involving PI3-kinase and Rac, IL-2 can induce profound
alterations of the T cell cytoskeleton, a phenomenon which might be of importance
for T cell physiology.
PMID- 9645370
TI - Thymic function in young/old chimeras: substantial thymic T cell regenerative
capacity despite irreversible age-associated thymic involution.
AB - Age-associated thymic involution results in a diminished capacity to regenerate T
cell populations, although the magnitude of this effect is unknown. In this
report, thymic function was studied in aged vs. young adult mice after lethal
irradiation and administration of T cell-depleted bone marrow (BM) from young
mice. Abnormalities observed in aged thymi (reduced thymocyte numbers, histologic
abnormalities) were not reversed by administration of young BM via bone marrow
transplantation (BMT), but aged thymi displayed a normal thymocyte subset
distribution and appropriately deleted MIs-reactive T cells after BMT. Aged BMT
recipients regenerated significantly reduced numbers of splenic T cells compared
to young recipients and showed increased peripheral expansion of thymic emigrants
since a higher proportion of BM-derived T cells expressed a memory phenotype in
aged vs. young BMT recipients. Because peripheral expansion of thymic emigrants
could substantially increase the number of thymic progeny present in the spleen,
we sought to measure thymic T cell regenerative capacity after BMT in a setting
devoid of peripheral expansion. To do this, TCR-transgenic (Tg+) T cell-depleted
BM was administered to aged and young recipients lacking antigen specific for the
Tg+ TCR. Aged recipients regenerated approximately 50 % of the TCR Tg+ cells
regenerated in young BMT recipients, providing evidence that even very aged thymi
retain the capacity to regenerate significant numbers of mature T cell progeny.
Therefore, thymic function is reduced with aged but it is not lost, suggesting
that therapeutic approaches to enhance thymic function may be successful even in
very aged hosts.
PMID- 9645371
TI - T cell recognition motifs of an immunodominant peptide of myelin basic protein in
patients with multiple sclerosis: structural requirements and clinical
implications.
AB - Myelin basic protein (MBP)-reactive T cells may play an important role in the
pathogenesis of multiple sclerosis (MS). The T cell response to the 83-99 region
of MBP represents a dominant autoreactive response to MBP in MS patients of DR2
haplotype. In this study, a large panel of DR2- and DR4-restricted T cell clones
specific for the MBP83-99 peptide were examined for the recognition motifs and
structural requirements for antigen recognition using alanine-substituted
peptides. Our study revealed that although the recognition motifs of the T cell
clones were diverse, the TCR contact residues within the 83-99 region of MBP were
highly conserved. Two central residues (Phe90 and Lys91) served as the critical
TCR contact points for both DR2- and DR4-restricted T cell clones. Single alanine
substitution at residue 90 or residue 91 abolished the responses of 81-95 % of
the T cell clones while a double alanine substitution rendered all T cell clones
unresponsive. It was also demonstrated in this study that the substituted
peptides altered the cytokine profile of some, but not all, T cell clones. Some
MBP83-99-specific T cell clones were able to sustain alanine substitutions and
were susceptible to activation by microbial antigens. The study has an important
implication in designing a peptide-based therapy for MS.
PMID- 9645372
TI - Identification of mimicry peptides based on sequential motifs of epitopes derived
from 65-kDa glutamic acid decarboxylase.
AB - Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a
predominantly non-hereditary etiology that results in a destruction of pancreatic
beta cells by autoaggressive T lymphocytes. Neither the mechanism of initial
stimulation of these T cells nor the nature of the environmental factors
implicated in the disease have so far been identified. However, both issues are
taken into account by the hypothesis of initial T cell activation by viral or
bacterial mimicry peptides with sequence similarities to pancreatic self
antigens. We determined sequential epitope motifs to search for mimicry peptides
stimulating T cell lines specific for two epitopes derived from the IDDM
autoantigen 65-kDa glutamic acid decarboxylase (GAD65). These were GAD65 (88-99),
presented by HLA-DRB1*0101, and GAD65 (248-257), presented by HLA-DRB5*0101. T
cell stimulation by peptides with substitutions in HLA anchor or T cell contact
positions was analyzed to establish degenerate epitope motifs for database
searching. Out of 28 tested candidate mimicry peptides derived from bacterial,
viral and human proteins, 3 stimulated T cell lines and a T cell clone specific
for epitope GAD65 (248-257). Our results demonstrate that mono- and polyclonal
GAD65-specific T cells from IDDM patients can be stimulated by viral and
bacterial peptides with little apparent sequence homology with autoantigenic
epitopes. Moreover, in a synopsis with related published studies, our findings
suggest that simple degenerate search motifs comprising principal T cell contacts
plus HLA class II binding motifs may suffice to identify most mimicry peptides.
PMID- 9645373
TI - Self-veto mechanism of CD8+ cytotoxic effector T cells. Peptide-induced paralysis
affects the peptide-MHC-recognizing cytotoxic T lymphocytes and is independent of
Fas/Fas ligand interactions.
AB - The lytic activity of CD8+ cytotoxic T lymphocyte (CTL) cell lines or clones can
be inhibited by addition of the peptide recognized by these cells. The mechanisms
underlying this phenomenon are not fully understood. Here we have analyzed
peptide-induced CTL paralysis using in vivo generated ovalbumin (OVA)-specific
CTL. Lytic activity of OVA-specific CTL was inhibited by addition of the
immunodominant OVA-peptide SIINFEKL in a dose-dependent manner. Paralysis was
induced rapidly and binding of the peptide to MHC class I molecules was required.
Using mixing experiments with CTL populations of different peptide specificities
restricted to the same MHC class I molecule we identified a veto-like mechanism:
the cytotoxic activity of the peptide-recognizing CTL was inhibited while the
lytic activity of the peptide-presenting CTL was unaltered. Only CD8+ CTL but not
CD4+ T cells or B+ cells induced paralysis. After removal of the peptide
presenting CTL by magnetic cell sorting, paralysis was maintained and paralyzed
CTL showed no signs of apoptosis. Loss of cytotoxicity could be induced in CTL
populations from Fas-deficient (lpr+/lpr+) or Fas ligand-deficient (gld+/gld+)
mice and mixtures thereof, implying that Fas/Fas ligand interactions are not
involved during induction of paralysis. Hence, peptide-induced paralysis of CTL
is due to a self-veto mechanism rather than to mutual killing of CTL. These
findings may have implications for in vivo immunization with peptides, viral
escape and peripheral tolerance mechanisms.
PMID- 9645374
TI - Dendritic cell/macrophage precursors capture exogenous antigen for MHC class I
presentation by dendritic cells.
AB - Presentation of MHC class I antigens by professional antigen-presenting cells
(APC) is an important pathway in priming cytotoxic T lymphocyte responses in
vivo. This study sought to identify the nature of the professional APC
responsible for indirect class I presentation by examining a special feature of
professional APC, namely their ability to process exogenous forms of antigen for
class I presentation. Incubation of highly purified bone marrow-derived precursor
cells with chicken ovalbumin (OVA) led to the efficient presentation of the major
class I-restricted OVA determinant by mature dendritic cells (DC), but not by
macrophages (Mphi) derived from the precursor population. DC as well as
macrophages were, however, able to mediate class II presentation of OVA,
suggesting that macrophages were deficient in class I processing but not in
capturing exogenous OVA. The majority of mature DC, i.e. over 80 %, generated
from the precursor cells pulsed with OVA, presented the class I OVA epitope. Upon
maturation, class I presentation of OVA by DC was greatly reduced, suggesting
that class I processing of exogenous antigen is modulated during DC maturation in
a manner similar to class II antigen processing. This study shows that bone
marrow-derived DC/ME progenitors capture exogenous antigen for class I
presentation, and that cells of the DC lineage can be functionally distinguished
from cells of the macrophage lineage based on their ability to process exogenous
antigen for class I presentation.
PMID- 9645375
TI - Naturally activated CD4+ T cells are highly enriched for cytokine-producing
cells.
AB - Most T cells in a normal non-immunized individual are in a resting state.
However, a small proportion of splenic T cells are large activated cells both in
specific pathogen-free and antigen-free mice. To further elucidate the effector
functions associated with these "naturally" activated CD4+ T cells, we have
characterized the expression of various membrane markers, cytokine production and
T helper activity by these cells. We show that naturally activated CD4+ T cells
express activation markers and contain tenfold higher proportions of cells
producing IL-4, IL-10 and IFN-gamma as compared to small CD4+ T cells. Despite
the high proportion of IFN-gamma producers, naturally activated CD4+ T cells
still induce B cell proliferation and differentiation. These results are
discussed in the context of normal physiological autoreactivity.
PMID- 9645376
TI - T cell cross-reactivity to heavy metals: identical cryptic peptides may be
presented from protein exposed to different metals.
AB - The mechanisms by which metals induce activation of T cells and thus produce
allergic and/ or autoimmune reactions are still obscure, and the same is true for
the mechanisms that underly T cell cross-reactivity to different heavy metal
ions. In the present study, we investigated induction by metals of T cell
reactions to cryptic peptides of bovine RNase A. Murine CD4+ T cell hybridomas
specific for cryptic RNase peptides presented from Au(III)-treated RNase were
used as detection probes. We showed that in vitro treatment of RNase with Pd(II),
Pd(IV), Ni(IV), and partially Pt(IV), but not Au(I), Ni(II), or Pt(II), induced
presentation of the same cryptic peptides as those presented from Au(III)-treated
RNase. That the former heavy metal ions, but not the latter, were able to alter
the antigenicity of RNase was reflected by their ability to induce conformational
changes of RNase, as detected by circular dichroism spectroscopy. Furthermore,
upon immunization against RNase pretreated with these metals, CD4+ T cell
hybridomas specific for unidentified cryptic peptides were obtained. In
conclusion, "metal-specific" T cell reactions may be directed against cryptic
peptides, and metal cross-reactivity in allergic individuals might be due to
metal-induced presentation of overlapping, but not identical, panels of cryptic
peptides.
PMID- 9645377
TI - Ligation of CD31/PECAM-1 modulates the function of lymphocytes, monocytes and
neutrophils.
AB - CD31 or platelet/endothelial cell adhesion molecule (PECAM-1) is a 130-kDa
glycoprotein expressed on endothelial cells, granulocytes, a subset of
lymphocytes and platelets. In this study, we examined the ability of four
monoclonal antibodies (mAb) against different domains of CD31 to modulate the
function of T lymphocytes, monocytes and neutrophils. Engagement of CD31 on T
lymphocytes results in co-stimulation of T lymphocyte proliferation to suboptimal
doses of anti-CD31 mAb. This proliferation is accompanied by secretion of
numerous cytokines and chemokines, up-regulation of CD25 and an increase in cell
size. Purification of T lymphocytes into CD45RO and CD45RA subsets showed that
only naive CD45RA T lymphocytes are co-stimulated by anti-CD31 mAb. Further
studies on neutrophils show that engagement of CD31 results in down-regulation of
CD62L and up-regulation of CD11b/CD18 as well as oxidative burst, as assessed by
superoxide release. In addition, ligation of CD31 on monocytes results in TNF
alpha secretion, and studies with various cell signaling inhibitors indicate that
tyrosine kinases and cAMP-dependent kinases are involved in monocyte activation
via CD31. Of the four mAb used in this study, only two activated human
leukocytes. These mAb were PECAM-1.3 and hec7, which bind to domains 1 and 2 of
CD31. We conclude that engagement of domains 1 and 2 of CD31 results in outside
in signaling in leukocytes.
PMID- 9645378
TI - Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice.
AB - The leukocyte integrin LFA-1 plays an important role in leukocyte trafficking and
the immune response. Using LFA-1-deficient mice, we demonstrate that LFA-1
regulates the trafficking of lymphocytes to peripheral lymph nodes, and, to a
lesser degree, to mesenteric lymph nodes and acute inflammatory sites. LFA-1,
either because of its role in initial adhesion and/ or the passage of leukocytes
across endothelial cells, plays a vital role in T lymphocyte and neutrophil
transendothelial migration. Neutrophils and activated T lymphocytes from LFA-1
deficient mice were unable to cross endothelial cell monolayers in response to a
chemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophils were
capable of migration. By contrast, LFA-1-deficient T lymphocytes displayed normal
chemotaxis to the same chemokine. Our studies with LFA-1-deficient monocytes
indicate that LFA-1 acts in concert with complement receptor 3 to mediate
transendothelial migration of these cells, as anti-CD18 monoclonal antibodies
(mAb) blocked both WT and LFA-1-deficient monocyte transendothelial migration,
whereas anti-CD11 b mAb preferentially blocked transendothelial migration of LFA
1-deficient monocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and
neutrophil transendothelial cell migration they did not block LFA-1-deficient
monocyte and neutrophil transendothelial migration.
PMID- 9645379
TI - Contribution of CD11a/CD18, CD11b/CD18, ICAM-1 (CD54) and -2 (CD102) to human
monocyte migration through endothelium and connective tissue fibroblast barriers.
AB - Recently we reported that monocyte migration through a barrier of human synovial
fibroblasts (HSF) is mediated by the CD11/CD18 (beta2) integrins, and the beta1
integrins VLA-4 and VLA-5 on monocytes. Here we investigated in parallel the role
of beta2 integrin family members, LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) on
monocytes, and the immunoglobulin supergene family members, ICAM-1 and ICAM-2 on
HSF and on human umbilical vein endothelial cells (HUVEC), in monocyte migration
through HSF and HUVEC monolayers. Using function blocking monoclonal antibodies
(mAb), when both VLA-4 and VLA-5 on monocytes were blocked, treatment of
monocytes with mAb to both LFA-1 and to Mac-1 completely inhibited monocyte
migration across HSF barriers, although blocking either of these beta2 integrins
alone had no effect on migration, even when VLA-4 and VLA-5 were blocked. This
indicates that optimal beta2 integrin-dependent monocyte migration in synovial
connective tissue may be mediated by either LFA-1 or Mac-1. Both ICAM-1 and ICAM
2 were constitutively expressed on HSF and on HUVEC, although ICAM-2 was only
minimally expressed on HSF. Based on results of mAb blockade, ICAM-1 appeared to
be the major ligand for LFA-1-dependent migration through the HSF. In contrast,
both ICAM-1 and ICAM-2 mediated LFA-1-dependent monocyte migration through HUVEC.
However, neither ICAM-1 nor ICAM-2 was required for Mac-1 -dependent monocyte
migration through either cell barrier, indicating that Mac-1 can utilize ligands
distinct from ICAM-1 and ICAM-2 on HSF and on HUVEC during monocyte
transmigration.
PMID- 9645380
TI - p49, a putative HLA class I-specific inhibitory NK receptor belonging to the
immunoglobulin superfamily.
AB - NK cells display several killer inhibitory receptors (KIR) specific for different
alleles of MHC class I molecules. A family of KIR are represented by type I
transmembrane proteins belonging to the immunoglobulin superfamily (Ig-SF).
Besides cDNA encoding for these KIR, additional cDNA have been identified which
encode for Ig-SF receptors with still undefined specificity. Here we analyze one
of these cDNA, termed cl.15.212, which encodes a type I transmembrane protein
characterized by two extracellular Ig-like domains and a 115-amino acid
cytoplasmic tail containing a single immuno-receptor tyrosine-based inhibitory
motif (ITIM) which is typical of KIR. cl.15.212 cDNA displays approximately 50 %
sequence homology with other Ig-SF members. Different from the other KIR,
cl.15.212 mRNA is expressed by all NK cells and by a fraction of KIR+ T cell
clones. cl.15.212 cDNA codes for a membrane-bound receptor displaying an apparent
molecular mass of 49 kDa, thus termed p49. To determine the specificity of the
cl.15.212-encoded receptor, we generated soluble fusion proteins consisting of
the ectodomain of p49 and the Fc portion of human IgG1. Soluble molecules bound
efficiently to 221 cells transfected with HLA-G1, -A3, -B46 alleles and weakly to
-B7 allele. On the other hand, they did not bind to 221 cells either
untransfected or transfected with HLA-A2, -B51, -Cw3 or -Cw4. The binding
specificity of soluble p49-Fc was confirmed by competition experiments using an
anti-HLA class I-specific monoclonal antibody. Finally, different cDNA encoding
for molecules homologous to cl.15.212 cDNA have been isolated, two of which lack
the sequence encoding the transmembrane portion, thus suggesting they may encode
soluble molecules.
PMID- 9645381
TI - NK cells differentiated from bone marrow, cord blood and peripheral blood stem
cells exhibit similar phenotype and functions.
AB - In the present study, we investigated the differentiation of human NK cells from
bone marrow, cord blood and mobilized peripheral blood purified CD34+ stem cells
using a potent culture system. Elutriated CD34+ stem cells were grown for several
weeks in medium supplemented with stem cell factor (SCF) and IL-15 in the
presence or absence of a murine stromal cell line (MS-5). Our data indicate that
IL-15 induced the proliferation and maturation of highly positive CD56+ NK cells
in both types of culture, although murine stromal cells slightly increased the
proliferation of NK cells. NK cells differentiated in the presence of MS-5 were
mostly CD56+ CD7 and a small subset expressed CD16. These in vitro differentiated
CD56+ NK cells displayed cytolytic activity against the HLA class I- target K562.
The CD56+ CD16+ subset also lysed NK-resistant Daudi cells. Neither of these NK
subsets were shown to express Fas ligand. Total CD56+ cells expressed high
amounts of transforming growth factor-beta and granulocyte-macrophage colony
stimulating factor, but no IFN-gamma. Investigation of NK receptor expression
showed that most CD56+ cells expressed membrane CD94 and NKG2-A mRNA. PCR
analysis revealed that p58 was also expressed in these cells. The role of CD94 in
NK cell-mediated cytotoxicity was assessed on human HLA-B7-transfected murine L
cells. While a low cytotoxic activity towards HLA-B7 cells was observed, the HLA
DR4 control cells were killed with high efficiency. These studies demonstrate
that cytolytic and cytokine-producing NK cells may be derived from adult and
fetal precursors by IL-15 and that these cells express a CD94 receptor which may
influence their lytic potential.
PMID- 9645382
TI - Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic
cells.
AB - Dendritic cells are the most relevant antigen-presenting cells (APC) for
presentation of antigens administered in adjuvant to CD4+ T cells. Upon
interaction with antigen-specific T cells, dendritic cells (DC) expressing
appropriate peptide-MHC class II complexes secrete IL-12, a cytokine that drives
Th1 cell development. To analyze the T cell-mediated regulation of IL-12
secretion by DC, we have examined their capacity to secrete IL-12 in response to
stimulation by antigen-specific Th1 and Th2 DO11.10 TCR-transgenic cells. These
cells do not differ either in TCR clonotype or CD40 ligand (CD40L) expression.
Interaction with antigen-specific Th1, but not Th2 cells, induces IL-12 p40 and
p75 secretion by DC. The induction of IL-12 production by Th1 cells does not
depend on their IFN-gamma secretion, but requires direct cell-cell contact
mediated by peptide/MHC class II-TCR and CD40-CD40L interactions. Th2 cells not
only fail to induce IL-12 secretion, but they inhibit its induction by Th1 cells.
Unlike stimulation by Th1, inhibition of IL-12 production by Th2 cells is
mediated by soluble molecules, as demonstrated by transwell cultures. Among Th2
derived cytokines, IL-10, but not IL-4 inhibit Th1-driven IL-12 secretion. IL-10
produced by Th2 cells appears to be solely responsible for the inhibition of Th1
induced IL-12 secretion, but it does not account for the failure of Th2 cells to
induce IL-12 production by DC. Collectively, these results demonstrate that Th1
cells up-regulate IL-12 production by DC via IFN-gamma-independent cognate
interaction, whereas this is inhibited by Th2-derived IL-10. The inhibition of
Th1 -induced IL-12 production by Th2 cells with the same antigen specificity
represents a novel mechanism driving the polarization of CD4+ T cell responses.
PMID- 9645383
TI - Inhibition of in vitro immunoglobulin production by IL-12 in murine chronic graft
vs.-host disease: synergism with IL-18.
AB - We investigated the effects of IL-12 on immunoglobulin (Ig) production in vitro
in murine chronic graft-vs. -host disease (cGVHD), a lupus-like model of overt B
cell activation induced by allogeneic stimulation. Addition of IL-12 to cGVHD
splenocytes strongly inhibited total Ig (Igkappa), IgM and IgG1 production.
Although IL-12 down-regulated IL-4, IL-5, IL-9 and IL-10 production, its
inhibitory activity on Ig production could not be ascribed to down-regulation of
these cytokines, as addition of saturating doses of IL-4, IL-5 and/or IL-9 did
not reverse the inhibitory activity of IL-12. Interestingly, IL-12 was also found
to suppress the stimulating effect of IL-4 and IL-5 on Ig synthesis by cGVHD
splenocytes. Several lines of evidence indicated that the inhibitory activity
exerted by IL-12 on Ig production was mediated by IFN-gamma. First, IFN-gamma was
produced in large amounts upon IL-12 stimulation. Secondly, it displayed a potent
inhibitory activity on Ig production. Thirdly, Ig production was also inhibited
by IL-18, a recently cloned IFN-gamma-inducing cytokine. Finally, the inhibitory
activity of IL-12 was blocked by anti-IFN-gamma monoclonal antibody. We also
investigated whether IL-12 down-regulated Ig production by purified cGVHD B
cells. We found that IL-12 had only a marginal inhibitory activity on highly
purified B cell populations isolated from cGVHD splenocytes and stimulated with
IL-4 and IL-5, and that IL-18 was inactive in this respect. However, when the two
cytokines were combined, a striking synergy was unmasked not only for IgG1
inhibition but also for IFN-gamma production by these B cell populations. Taken
together, our results demonstrate that IL-12 inhibits in vitro Ig production by
activated splenocytes through IFN-gamma production and that it synergizes with IL
18 on activated B cells to inhibit Ig production, through up-regulation of IFN
gamma production by B cells.
PMID- 9645384
TI - The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal
lymphoid tissues and attracts activated T cells via CCR7.
AB - Secondary lymphoid-tissue chemokine, SLC, also known as exodus-2 and 6Ckine, is a
novel CC chemokine with selectivity for T lymphocytes and preferential expression
in lymphoid tissues. We have studied its production, receptor usage and
biological activities. High levels of SLC mRNA were detected in lymph nodes, the
gastrointestinal tract and several gland tissues, but no expression was found by
Northern blot analysis in freshly isolated or stimulated blood monocytes and
lymphocytes, or neutrophils and eosinophils. In situ hybridization revealed
constitutive expression of SLC in the T cell areas and the marginal zone of
follicles in lymph nodes and the mucosa-associated lymphoid tissue, but not in B
cell areas or sinuses. Comparison with immunocytochemical staining showed
similarity between the in situ expression of SLC and the distribution of
interdigitating dendritic cells but not with sinus-lining dendritic cells,
macrophages or T lymphocytes. SLC induced chemotaxis of T lymphocytes and its
activity increased considerably when the cells were conditioned with IL-2 or
phytohemagglutinin (PHA). Under optimal conditions SLC had unusually high
efficacy and induced the migration of up to 50 % of input T lymphocytes. SLC also
induced Ca2+ mobilization in these cells. Similar responses were obtained with
EBI1 ligand chemokine (ELC), and sequential stimulation with both chemokines led
to cross-desensitization, suggesting that SLC acts via the ELC receptor, CCR7.
This was confirmed using murine pre-B cells stably transfected with CCR7 which
bound SLC with high affinity and showed chemotaxis and Ca2+ mobilization in
response to both SLC and ELC. In T lymphocytes PHA and IL-2, which enhanced
chemotactic responsiveness, also markedly enhanced CCR7 expression. In contrast
to all known chemokine receptors, up-regulation of CCR7 by IL-2 was transient. A
maximum was reached in 2-3 days and expression returned to initial levels within
8-10 days. The present study shows that SLC is constitutively produced within the
T cell areas of secondary lymphoid organs and attracts T lymphocytes via CCR7.
PMID- 9645385
TI - Suppression of experimental autoimmune encephalomyelitis with a TNF binding
protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4.
AB - The effect of a novel TNF binding protein (TNFbp), a polyethylene glycol-linked
form of the type I soluble receptor of TNF, on the expression of adhesion
molecules has been investigated with a passive transfer model of experimental
autoimmune encephalomyelitis (EAE) in SJL/J mice. The expression of L-selectin,
VLA-4 and LFA-1 on spleen cells of EAE animals treated with TNFbp or saline was
examined by FACS analysis. The expression of VCAM-1 and ICAM-1 was investigated
by immunochemistry in spinal cord tissue of SJL/J mice with EAE. In animals
sensitized for EAE and treated with TNFbp, the expression of VCAM-1 in the
central nervous system as well as VLA-4 on spleen cells was clearly diminished.
Reduction in VCAM-1 staining and VLA-4 expression corresponded to inhibition of
inflammation in the spinal cord and to prevention of clinical signs of EAE. The
results have also shown that myelin basic protein responses as well as non
antigen-specific responses were not diminished in animals treated with TNFbp. The
findings suggest that TNFbp might prevent EAE development by modulating the
expression of VCAM-1 and VLA-4.
PMID- 9645386
TI - Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and
activation of murine dendritic cells.
AB - Bacterial DNA and immunostimulatory (i.s.) synthetic CpG-oligodeoxynucleotides
(ODN) act as adjuvants for Th1 responses and cytotoxic T cell responses to
proteinaceous antigens. Dendritic cells (DC) can be referred to as "nature's
adjuvant" since they display the unique capacity to sensitize naive T cells.
Here, we demonstrate that bacterial DNA or i.s. CpG-ODN cause simultaneous
maturation of immature DC and activation of mature DC to produce cytokines. These
events are associated with the acquisition of professional antigen-presenting
cell (APC) function. Unfractionated murine bone marrow-derived DC and FACS
fractionated MHC class IIlow (termed immature DC) or MHC class IIhigh populations
(termed mature DC) were stimulated with bacterial DNA or i.s. CpG-ODN. Similar to
lipopolysaccharide, i.s. CpG-ODN caused up-regulation of MHC class II, CD40 and
CD86, but not CD80 on immature and mature DC. In parallel both DC subsets were
activated to produce large amounts of IL-12, IL-6 and TNF-alpha. CpG-ODN
activated DC displayed professional APC function in allogeneic mixed lymphocyte
reaction and in staphylococcal enterotoxin B-driven naive T cell responses. We
interpret these findings to mean that bacterial DNA and i.s. CpG-ODN cause
maturation (first step) and activation (second step) of DC to bring about
conversion of immature DC into professional APC.
PMID- 9645387
TI - Hypothesis: are fatty acid patterns characteristic of essential fatty acid
deficiency indicative of oxidative stress?
AB - Several unrelated diseases show plasma and tissue fatty acid patterns
characteristic of those seen in Essential Fatty Acid Deficiency Disease (EFADD).
A common feature occurring in all these diseases is oxidative stress. We
hypothesize that reactive oxygen species or products of oxidative damage,
particularly those derived from lipids, act as signal molecules to alter
desaturase enzymes and induce the fatty acid patterns characteristic of EFADD.
PMID- 9645388
TI - The oxidative inactivation of tissue inhibitor of metalloproteinase-1 (TIMP-1) by
hypochlorous acid (HOCI) is suppressed by anti-rheumatic drugs.
AB - Tissue inhibitors of metalloproteinases (TIMPs) prevent uncontrolled connective
tissue destruction by limiting the activity of matrix metalloproteinases (MMPs).
That TIMPs should be susceptible to oxidative inactivation is suggested by their
complex tertiary structure which is dependent upon 6 disulphide bonds. We
examined the oxidative inactivation of human recombinant TIMP-1 (hr TIMP-1) by
HOCl and the inhibition of this process by anti-rheumatic agents. TIMP-1 was
exposed to HOCl in the presence of a variety of disease modifying anti-rheumatic
drugs. TIMP-1 activity was measured by its ability to inhibit BC1 collagenase
activity as measured by a fluorimetric assay using the synthetic peptide
substrate (DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg), best cleaved by MMP-1. The
neutrophil derived oxidant HOCl, but not the derived oxidant N-chlorotaurine, can
inactivate TIMP-1 at concentrations achieved at sites of inflammation. Anti
rheumatic drugs have the ability to protect hrTIMP-1 from inactivation by HOCl.
For D-penicillamine, this effect occurs at plasma levels achieved with patients
taking the drug but for other anti-rheumatic drugs tested this occurs at
relatively high concentrations that are unlikely to be achieved in vivo, except
possibly in a microenvironment. These results are in keeping with the concept
that biologically derived oxidants can potentiate tissue damage by inactivating
key but susceptible protein inhibitors such as TIMP-1 which form the major local
defence against MMP induced tissue breakdown.
PMID- 9645389
TI - Studies of the cellular distribution of superoxide dismutases in adult and fetal
rat tissues.
AB - Activities of three types of superoxide dismutase in tissue fractions were
significantly lower in fetal and adult brain and fetal limb preparations than in
fetal and adult heart preparations. An exception was the cytoplasmic fraction of
adult brain that had levels of Cu, Zn-superoxide dismutase activity comparable to
those in cytoplasmic fractions of heart. In addition, Mn superoxide dismutase
activity appeared to be very low in all fetal mitochondrial matrix fractions and
cytoplasmic fractions as well as in adult brain. Finally, the results of these
studies emphasize the importance of two antioxidant defense systems in the
tissues studied, one associated with the mitochondrial electron transport system
and the other, the cytosolic Cu, Zn enzyme.
PMID- 9645390
TI - Prevention of intracellular oxidative stress to lens by pyruvate and its ester.
AB - Pyruvate is a well-known scavenger of hydrogen peroxide (H2O2). In addition, it
scavenges superoxide radical (O2.-). However, evidence on its intracellular
antioxidant function is meager at present. Hence, we have examined the
effectiveness of this metabolite and its ethyl ester against intracellular
oxidative damage to the lens under organ culture. Menadione, a redoxcycling
quinone, was used to generate the reactive oxygen species (ROS). It was found to
inhibit lens metabolism as evidenced by a decrease of ATP. Additionally, tissue
oxidation was apparent by loss of glutathione (GSH), and increase in the level of
oxidized glutathione (GSSG), coupled with increase of the urea soluble proteins
(water insoluble). The overall physiological damage was apparent by the
inhibition of the Na+-K+-ATPase dependent cation pump, as evidenced by a
decreased rubidium transport. These deleterious effects were attenuated by
pyruvate and ethyl-pyruvate. The later was found to be more effective.
PMID- 9645391
TI - Evidence against the involvement of multiple radical generating sites in the
expression of the vascular cell adhesion molecule-1.
AB - The present study was undertaken to investigate the hypothesis that multiple
oxygen radical generating systems contribute to the tumor necrosis factor (TNF)
alpha-stimulated transcriptional activation of the vascular cell adhesion
molecule (VCAM)-1 in endothelial cells. Experimental evidence has implicated the
cytochrome P450 monooxygenase and a phagocyte type NADPH-oxidase as a source of
oxygen radicals in these cells. We show here that endothelial cells exhibit
cytochrome P450 activity by measuring the O-dealkylation of the exogenous
substrate 7-ethoxyresorufin, but components of the phagocyte-type NADPH oxidase
could not be demonstrated in endothelial cells. In that latter respect it was
surprising that the NADPH oxidase inhibitor apocynin completely prevented the
accumulation of VCAM-1 mRNA. However, we found that apocynin also acts as an
inhibitor of cytochrome P450 activity in endothelial cells. Therefore the
inhibitory effect of apocynin on the induction of VCAM-1 may no longer be used to
demonstrate a role for the NADPH oxidase in this process. Furthermore, different
cytochrome P450 inhibitors Co2+, metyrapone, SKF525a decreased the endothelial
VCAM-1 expression stimulated by TNFalpha. Also under hypoxic conditions the
expression of VCAM-1 was reduced. On this basis we assume that the oxygen
dependent step in the intracellular signalling cascade underlying the TNFalpha
stimulated transcriptional activation of VCAM-1 resides in the activity of a
cytochrome P450 dependent monooxygenase. The finding that the phospholipase A2
inhibitor bromophenacylbromide inhibited the expression of VCAM-1 may indicate
that arachidonic acid serves as a substrate for the cytochrome P450 monooxygenase
reaction, but further research is needed to elucidate the particular cytochrome
P450 family member mediating the expression of VCAM-1.
PMID- 9645392
TI - A reappraisal of xanthine dehydrogenase and oxidase in hypoxic reperfusion
injury: the role of NADH as an electron donor.
AB - Xanthine oxidase (XO) is conventionally known as a generator of reactive oxygen
species (ROS) which contribute to hypoxic-reperfusion injury in tissues. However,
this role for human XO is disputed due to its distinctive lack of activity
towards xanthine, and the failure of allopurinol to suppress reperfusion injury.
In this paper, we have employed native gel electrophoresis together with activity
staining to investigate the role human xanthine dehydrogenase (XD) and XO in
hypoxic reperfusion injury. This approach has provided information which cannot
be obtained by conventional spectrophotometric assays. We found that both XD and
XO of human umbilical vein endothelial cells (HUVECs) and lymphoblastic leukaemic
cells (CEMs) catalysed ROS generation by oxidising NADH, but not hypoxanthine.
The conversion of XD to XO was observed in both HUVECs and CEMs in response to
hypoxia, although the level of conversion varied. Purified human milk XD
generated ROS more efficiently in the presence of NADH than in the presence of
hypoxanthine. This NADH oxidising activity was blocked by the FAD site inhibitor,
diphenyleneiodonium (DPI), but was not suppressible by the molybdenum site
inhibitor, allopurinol. However, in the presence of both DPI and allopurinol the
activities of XD/XO were completely blocked with either NADH or hypoxanthine as
substrates. We conclude that both human XD and XO can oxidise NADH to generate
ROS. Therefore, the conversion of XD to XO is not necessary for post-ischaemic
ROS generation. The hypoxic-reperfusion injury hypothesis should be reappraised
to take into account the important role played by XD and XO in oxidising NADH to
yield ROS.
PMID- 9645393
TI - In vitro inhibition by N-acetylcysteine of oxidative DNA modifications detected
by 32P postlabeling.
AB - Reactive oxygen species are involved in the pathogenesis of cancer and other
chronic degenerative diseases through a variety of mechanisms, including DNA
damage. We investigated by 32p and 33P postlabeling analyses the nucleotidic
modifications induced in vitro by treating calf thymus DNA with H2O2 and CuSO4,
interacting in a Fenton type reaction. Six different enrichment procedures and
three chromatographic systems were comparatively assayed. The chromatographic
system using phosphate/urea, which is more suitable for detecting bulky DNA
adducts, was rather insensitive. In contrast, the system using acetic
acid/ammonium formate revealed high levels of mononucleotidic modifications. In
terms of ratio of adduct levels in treated and untreated DNA, the enrichment
procedures ranked as follows: nuclease P1 (19.6), no enrichment (18.3), digestion
to trinucleotides (17.6), digestion to monophosphate mononucleotides (8.4),
digestion to dinucleotides (3.4), and extraction with butanol (<1.0). The system
using formic acid/ammonium formate was quite efficient in detecting 8-hydroxy-2'
deoxyguanosine. Labeling with 33p further enhanced the sensitivity of the method.
The oxidative damage was so intense to produce a strong DNA fragmentation
detectable by agarose gel electrophoresis, and nucleotidic modifications were
more intense when DNA fragmentation was greater. The DNA alterations produced by
H2O2 alone were significantly lower than those produced following reaction of
H2O2 with CuSO4. The thiol N-acetylcysteine (NAC) was quite efficient in
inhibiting both nucleotidic modifications and DNA fragmentation produced in vitro
by either H2O2 or the .OH generating system. These results support at a molecular
level the findings of previous studies showing the ability of NAC to inhibit the
genotoxicity of peroxides and of reactive oxygen species generated by electron
transfer reactions.
PMID- 9645394
TI - Nitric oxide production in human macrophagic cells phagocytizing opsonized
zymosan: direct characterization by measurement of the luminol dependent
chemiluminescence.
AB - When differentiated into mature macrophages by the combination of all-trans
retinoic acid and 1,25-dihydroxyvitamin D3, the human promonocytic cell lines
U937 and THP-1 expressed inducible nitric oxide synthase (iNOS) transcripts.
During their differentiation, the cells acquired the capacity to produce not only
superoxide anion (O2.-) but also nitric oxide (.NO) in response to IgG (or IgE)
opsonized zymosan. The inhibitors of the iNOS pathway, aminoguanidine and NG
monomethyl-L-arginine (L-NMMA), suppressed the production of .NO and enhanced the
steady-state concentration of O2.- determined. Conversely, superoxide dismutase
(SOD) scavenged the O2.- released and increased the .NO-derived nitrite
concentration detected. These data suggested a possible interaction between O2.-
and .NO. In differentiated U937 (or THP-1) cells, IgG or IgE-opsonized zymosan
induced a strong time-dependent luminol-dependent chemiluminescence (LDCL), which
was abrogated by SOD and partially inhibited by aminoguanidine or L-NMMA. Since
the iNOS inhibitors did not directly scavenge O2.-, LDCL determination in the
presence or absence of SOD and/or iNOS inhibitors demonstrated a concomitant
production of O2.- and .NO. These radicals induced the formation of a .NO-derived
product(s), probably peroxynitrite (ONOO-), which was required to elicit maximal
LDCL. Finally, LDCL measurement provided a convenient tool to characterize iNOS
triggering and demonstrated an interaction between NADPH oxidase and iNOS
products in human macrophagic cells phagocytizing opsonized-zymosan. These
findings show that in activated macrophages, iNOS activity can be involved in
LDCL and support the debated hypothesis of iNOS participation to the microbicidal
activity of human macrophages.
PMID- 9645395
TI - Peroxynitrite causes aspartate release from dissociated rat cerebellar granule
neurones.
AB - Peroxynitrite (ONOO-) is a powerful oxidant which is formed from the reaction
between nitric oxide (NO) and superoxide anion. It has therefore been proposed to
mediate the toxic actions caused by NO. Since ONOO- may be formed in the central
nervous system (CNS) in pathological conditions such as brain ischaemia, we
decided to investigate whether this molecule induces the release of the
endogenous excitatory amino acids glutamate and aspartate from neurones. We
selected as biological model acutely dissociated rat cerebellar granule neurones
in suspension to allow a direct interaction between ONOO- and target cells.
Peroxynitrite caused a concentration-dependent release of aspartate but not of
glutamate from dissociated cerebellar granule neurones. Peroxynitrite-induced
aspartate release was inhibited by dithiothreitol, tetrodotoxin, and in Na+
deprived solutions and not affected by EGTA or pre-incubation with the cytosolic
Ca2+ chelator BAPTA/AM. Peroxynitrite also induced an increase in intracellular
Ca2+ concentration which was not affected in the presence of EGTA. These data
show that ONOO- causes release of aspartate from cerebellar granule neurones and
that this effect might arise from an alteration of Na+ membrane permeability
leading subsequently to reversal of a Na+-dependent plasma membrane transporter
of this excitatory amino acid. In addition, ONOO- alters Ca2+ homeostasis likely
due to Na+ overload. Taken together, these findings may help and elucidate some
of the intimate mechanisms of NO-induced neuronal damage in pathological
circumstances.
PMID- 9645396
TI - Chain-breaking antioxidants and ferriheme-bound drugs are synergistic inhibitors
of erythrocyte membrane peroxidation.
AB - Induced erythrocyte membrane peroxidation (EMP) is considered as an accurate
model of reperfusion injuries and as such was used to investigate protective
effects of various drugs. EMP was induced by an azo initiator and monitored by
oxygen uptake. Both hydrophilic (ascorbic acid) and lipophilic (alpha-tocopherol,
probucol, nicanartine) chain-breaking antioxidants as well as ferriheme-bound
drugs (deferoxamine, chloroquine) inhibited EMP. When antioxidants and ferriheme
bound drugs were combined, synergistic effects were observed. It is proposed that
ferriheme compounds which catalyse peroxide induced lipid peroxidation were
blocked by deferoxamine and/or chloroquine. So these drugs inhibited at least
partly the membrane peroxidation process and added their effects to the ones of
chain-breaking antioxidants.
PMID- 9645397
TI - Reactivity of cartilage and selected carbohydrates with hydroxyl radicals: an NMR
study to detect degradation products.
AB - It was investigated to what extent isolated, monomeric and polymeric
carbohydrates as well as cartilage specimens are affected by hydroxyl radicals
generated by gamma-irradiation or Fenton reaction and what products can be
detected by means of NMR spectroscopy. Resonances of all protons in glucose and
other monosaccharides as well as carbon resonances in 13C-enriched glucose were
continuously diminished upon gamma-irradiation. Formate and malondialdehyde were
found as NMR detectable products in irradiated glucose solutions under
physiologically relevant (aerated) conditions. In polysaccharide solutions (e.g.
hyaluronic acid) gamma-irradiation and also treatment with the Fenton reagent
caused first an enhancement of resonances according to mobile N-acetyl groups at
2.02 ppm. This indicates a breakdown of glycosidic bonds in polysaccharides.
Using higher radiation doses or higher concentrations of the Fenton reagent
formate was also detected. The same sequence of events was observed upon
treatment of bovine nasal cartilage with the Fenton reagent. First, glycosidic
linkages in cartilage polysaccharides were cleaved and subsequently formate was
formed. In contrast, collagen of cartilage was affected only to a very low
extent. Thus, HO-radicals caused the same action on cartilage as on isolated
polymer solutions, inducing a fragmentation of polysaccharides and the formation
of formate.
PMID- 9645398
TI - Redox properties of iron in the binding site(s) of F1ATPase from mammalian
mitochondria and thermophilic bacterium PS3: a comparative study.
AB - Iron ions in the two iron centers of beef heart mitochondrial F1ATPase, which we
have been recently characterized (FEBS Letters 1996, 379, 231-235), exhibit
different redox properties. In fact, the ATP-dependent site is able to maintain
iron in the redox state of Fe(II) even in the absence of reducing agents, whereas
in the nucleotide-independent site iron is oxidized to Fe(III) upon removal of
the reductant. Fe(III) ions in the two sites display different reactivity towards
H2O2, because only Fe(III) bound in the nucleotide-independent site rapidly
reacts with H2O2 thus mediating a 30% enzyme inactivation. Thermophilic bacterium
PS3 bears one Fe(III) binding site, which takes up Fe(III) either in the absence
or presence of nucleotides and is unable to maintain iron in the redox state of
Fe(II) in the absence of ascorbate. Fe(III) bound in thermophilic F1ATPase in a
molar ratio 1:1 rapidly reacts with H2O2 mediating a 30% enzyme inactivation.
These results support the presence in mitochondrial and thermophilic F1ATPase of
a conserved site involved in iron binding and in oxidative inactivation, in which
iron exhibits similar redox properties. On the other hand, at variance with
thermophilic F1ATPase, the mitochondrial enzyme has the possibility of
maintaining one equivalent of Fe(II) in its peculiar ATP-dependent site, besides
one equivalent of Fe(III) in the conserved nucleotide-independent site. In this
case mitochondrial F1ATPase undergoes a higher inactivation (75%) upon exposure
to H2O2. Under all conditions the inactivation is significantly prevented by PBN
and DMSO but not by Cu, Zn superoxide dismutase, thus suggesting the formation of
OH radicals as mediators of the oxidative damage. No dityrosines, carbonyls or
oxidized thiols are formed. In addition, in any cases no protein fragmentation or
aggregation is observed upon the treatment with H2O2.
PMID- 9645399
TI - Comments on a commentary: statistical evaluation of split mouth caries trials.
AB - When results of split mouth caries trials are reported, the most frequently used
outcome measures are "effectiveness" and "net gain". In a recent review by
Riordan & FitzGerald (Community Dent Oral Epidemiol 1994;22:192-7) of the
statistical analysis of data from such trials, the close connection between
effectiveness and the traditional epidemiological outcome measure, relative risk,
was pointed out and the latter measure was recommended. The confidence intervals
for these parameters were, however, incorrect. This note provides valid
confidence intervals for net gain, effectiveness and relative risk based on data
from split mouth trials and presents examples of the calculations.
PMID- 9645400
TI - Design and analysis issues in split mouth clinical trials.
PMID- 9645401
TI - Impact of diagnostic criteria on the prevalence of dental caries in Norwegian
children aged 5, 12 and 18 years.
AB - The study aimed to investigate caries prevalence in children using a severity
grading diagnostic system, and to evaluate the influence of different diagnostic
thresholds on the caries data. A group of 513 children, aged 5, 12 and 18 years,
were examined clinically, and with available bitewing radiographs, by four
calibrated examiners. The inter- and intra-examiner reliability, assessed by a
weighted kappa, varied between 0.80 and 0.95. The mean dmft/DMFT values were 3.8,
5.8 and 11.0 for the three age groups respectively, and the corresponding
dmfs/DMFS values were 5.4, 9.9 and 22.6. The d/D-component constituted the major
part of the dmf/DMF index in all age groups, and enamel lesions accounted for
59%, 89% and 86% of the d/D-component in the three age groups respectively. It is
concluded that enamel or initial caries lesions contributed substantially to the
total caries prevalence, illustrating the importance of using diagnostic criteria
that include all stages of clinical caries if a total picture of the caries
situation is needed.
PMID- 9645402
TI - Satisfaction with dental care among elderly Finnish men.
AB - To study satisfaction with dental care among elderly Finnish men and to estimate
the role of different factors affecting it, a questionnaire was sent to a
systematic sample of 2043 elderly Finnish men (mean age 73 years). Acceptably
filled-out questionnaires were returned by 1561, a participation rate of 76.4%.
The questionnaire included 44 questions concerning dental and denture services
and a modified 14-item Dental Satisfaction Questionnaire. The subjects were asked
to express how strongly they agreed or disagreed with each of the 14 statements.
These were later transformed and recoded to indicate level of satisfaction from
+2 (very satisfied) to -2 (very dissatisfied). Overall satisfaction was estimated
by summing up all the 14 scores. Dentate subjects were significantly (P<0.01)
more satisfied than the edentulous. Subjects were least satisfied with dental
care fees and most satisfied with accessibility and availability of services.
Dentate subjects viewed almost all 14 items significantly more favorably than did
the edentulous. Economics was seen to have a strong influence on dissatisfaction
with dental care fees, which was related to income level. Maintaining the
remaining dentition and supporting the dentition with fixed or removable dentures
seem to be the means to increase satisfaction among the dentate. The benefits of
belonging to a clinic's recall system should be explained thoroughly to the
elderly.
PMID- 9645403
TI - Tooth and tooth surface survival rates in birth cohorts from 1965, 1970, 1975,
and 1980 in Lahti, Finland.
AB - Differences in the tooth and tooth surface survival rates between four cohorts
born in 1965, 1970, 1975, and 1980 were analysed in a historical cohort study
including data on the permanent teeth of children aged 5-7 years at baseline and
19 years at the end of the study. A statistically significant reduction in caries
occurrence in fissured surfaces in the three oldest cohorts was seen during the 3
years after the eruption of the teeth. Caries occurrence in the cohorts born in
1975 and 1980 did not differ from each other. The occurrence of caries in smooth
surfaces was low in all age cohorts. Therefore, despite a systematic decrease in
caries occurrence towards the younger cohorts, no significant differences were
found between the cohorts in smooth surface decay. After the 3 first posteruptive
years, practically no differences in survival rates between the cohorts were
observed. In the two youngest cohorts, the figures during the 3 first years after
eruption did not differ from the figures for the later years. Throughout the
study, caries occurrence was symmetric and no gender differences were observed.
No postponement of decay was found by the end of the follow-up time.
PMID- 9645404
TI - Does dental service utilization drop during economic recession? The example of
Finland, 1991-94.
AB - After enjoying rapid economic growth in the 1980s, Finland suffered a deep
economic recession that began in 1990. It has been claimed that recession and
uneven subsidies influence the use of dental services negatively. Finnish adults
born after 1956 and world war veterans are entitled to subsidized dental care
either in the Public Dental Service (PDS) or in the private sector. Other adults
pay their treatment costs. OBJECTIVES: The purpose of this paper is to determine
whether the economic recession in Finland during the early 1990s affected the use
of dental services. METHODS: The data were collected by the National Research and
Development Centre for Welfare and Health using a method called CATI (Computer
Assisted Telephone Interview). The target population was non-institutionalized
persons aged 25-79 years. RESULTS: About one-third of those interviewed had
visited a dentist during the previous 6 months and this proportion was stable
during the years studied. Number of teeth, length of education, income and sex
had the highest predictive values for use of dental services as analyzed by
multiple logistic regression. Two-thirds had visited a private practitioner, one
third a PDS clinic and a small percentage some other dentist or denturist.
CONCLUSIONS: The results showed that the dental service utilization by Finns was
stable during this period of economic downturn and only minor changes occurred in
the mean number of visits. The most prominent change was seen in the youngest age
group, among whom dental utilization decreased by almost 10%. The study indicated
that subsidies do not strongly affect dental utilization today.
PMID- 9645405
TI - Approximal caries and sugar consumption in Icelandic teenagers.
AB - The aim of this study, conducted in 1994, was to examine the association between
approximal caries and sugar consumption in teenagers residing in three fluoride
deficient areas in Iceland while controlling for a number of behavioral,
residential and microbiological factors. One hundred and fifty subjects (mean age
14 years) selected from the Icelandic Nutritional Survey (INS) were examined
radiographically and they completed questionnaires about sugar consumption
frequency. Total grams of sugar intake were obtained from the INS for each
subject. Caries experience on approximal surfaces, diagnosed from radiographs,
was used as the dependent variable in the analyses. Altogether 45.2% of subjects
were caries free on approximal surfaces. The overall sample was found to have a
mean DFS on approximal surfaces of 2.73 (s=4.36) per subject. Average daily total
sugar intake was 170 g per subject and the mean number of sugar-eating occasions
between meals was 5.32 (s=6.29) per subject. The regression model indicated that
the frequency of between-meal sugar consumption was associated with approximal
caries, with frequency of candy consumption being the most important of the sugar
variables. In multivariate analysis, no relationship was found between dental
caries and total daily intake of sugar, although a significant relationship
between total sugar consumption and presence of caries was seen in bivariate
analysis. Between-meal consumption of sugar remains a risk factor for the
occurrence of dental caries, especially in populations with moderate-to-high
levels of dental caries experience.
PMID- 9645406
TI - A practice-based study on stepwise excavation of deep carious lesions in
permanent teeth: a 1-year follow-up study.
AB - This study reports results from a practice-based study in which deep carious
lesions were treated by general dental practitioners using stepwise excavation.
The material comprised 94 teeth with deep carious lesions which the clinicians
considered would result in pulp perforation if treated by a single and terminal
excavation. At the first visit excavation of the peripheral dentine was
completed. The outermost part of the central and necrotic dentine was gently
removed with a sharp excavator. Standardized assessments of the dentine colour
and consistency were made before application of a calcium hydroxide-containing
base material and temporary filling. The final excavation was completed after a
treatment interval ranging from 2 to 19 months, with a median of 6 months.
Reassessments of the dentine colour and consistency were made before complete
removal of demineralized dentine. The central dentine was significantly browner
and less softened after the sealing period. After removal of the dark-brownish
dentine during the final excavation, the colour and consistency of the exposed
central dentine was found to resemble that of the completely excavated peripheral
dentine. Only five cases resulted in pulp perforation during the final
excavation. The high success rate of teeth surviving the final treatment without
pulp exposure after 1 year of observation shows that it was possible for dentists
in general practice to administer and manage the treatment of deep carious
lesions, a process which may prolong tooth survival compared with conventional
endodontic techniques.
PMID- 9645407
TI - Stability of dental health behavior: a 3-year prospective cohort study of 15-, 16
and 18-year-old Norwegian adolescents.
AB - There is a need for a descriptive epidemiology of patterns of dental health
behavior through adolescence. OBJECTIVES: The purpose of this study was to assess
the tracking (degree of stability) of several categories of self-reported dental
health behavior in adolescence over a 3-year period. METHODS: In 1992, a
representative sample of 970 15-year-old adolescents of Hordaland county, Norway,
completed questionnaires under supervision at school. Postal follow-up studies 1
and 3 years later provided 709 and 781 answers, respectively. The present
analyses included 581 adolescents who participated on all three occasions and 670
adolescents who replied in 1992 and 1995. Paired sample t-tests, cross
tabulations and Pearson's correlation coefficients were used to assess stability.
For use in the cross-tabulations all variables were transformed into binary
categories (active and inactive). RESULTS: A substantial proportion of
adolescents remained consistently in the same behavioral category for all 3
survey years. Toothbrushing (80%) and use of dental floss (64%) were the most
stable activities, while consumption of sugared mineral water (53%), intake of
chocolate/sweets (52%) and use of F-rinse (54%) were less stable. However,
Pearson's correlations between corresponding behaviors assessed in 1992 and 1995
were moderate and varied from 0.59 (toothbrushing) to 0.22 (F-rinse) (P<0.001).
CONCLUSION: The results do not conclusively indicate a pattern of tracking. The
tendency is, however, clear enough to support the assumption that dental health
behavior continues during adolescence into adulthood.
PMID- 9645408
TI - Satisfaction as a determinant of compliance.
AB - In this study the relation between satisfaction and compliance is examined in
terms of specificity and predictive value. Satisfaction is assumed to be a
determinant of compliance, especially if both concepts are measured at the same
level of specificity (i.e., a dental level). A total of 176 subjects reported
their satisfaction with dental visits and the dental practice, their dental
compliance and their general tendency to comply. The results show a relation
between satisfaction and compliance and that compliance can be predicted by
satisfaction. Surprisingly, the relation between dental satisfaction and general
compliance is stronger than the relation between dental satisfaction and dental
compliance. This finding can be explained by the possible relation between
different levels of compliance and the complexity of the concept dental
compliance.
PMID- 9645409
TI - Treatment of amyloidosis and the rheumatologist. State of the art and
perspectives for the future.
AB - The rheumatologist must be prepared to face diagnostic and therapeutic problems
related to different categories of amyloidosis. This applies to the systemic AA
amyloidosis that complicates chronic inflammatory arthropathies like adult and
juvenile rheumatoid arthritis, causing nephropathy and various internal
manifestations. Other types of amyloidosis are essential because they may
localize to structures of the locomotor system and cause rheumatic complaints. At
present, there is no cure for amyloidosis. But adequate and especially early
therapeutic intervention is helpful in many cases. This review focuses on
treatment of the categories of amyloidosis which are most relevant to the
rheumatologist. In addition to treatments that are available today, more
effective therapeutic modalities which hopefully will be available in the near
future are also reviewed.
PMID- 9645410
TI - Allergic disorders in primary Sjogren's syndrome.
AB - Allergic disorders have been described in a variety of connective tissue
disorders. Although an association between allergy and primary Sjogren's syndrome
has been suggested, it has not been well documented. The purpose of this study
was to analyze the prevalence of several types of allergic disorders in a cohort
of primary Sjogren's syndrome patients. The presence of an allergic disorder was
evaluated by a specific questionnaire in 65 randomly selected primary Sjogren's
syndrome patients and was compared to control groups of 67 rheumatoid arthritis
patients, 53 patients with rheumatoid arthritis and sicca symptoms, and 31
patients with osteoarthritis. At least one type of allergic manifestation was
reported by 42 of the 65 Sjogren's syndrome patients (65%). This rate was
significantly higher than each of the three control groups (p < 0.01). Only drug
allergy and skin contact allergy were found to be more prevalent in Sjogren's
syndrome patients than in the control groups (p< 0.05). Allergic reactions were
more common in Sjogren's syndrome patients who were anti-Ro positive (p < 0.05).
As drug and skin contact allergies are a frequent finding in Sjogren's syndrome
patients, obtaining a careful history is needed before prescribing drugs in these
patients.
PMID- 9645411
TI - Laboratory screening for side effects of disease modifying antirheumatic drugs in
daily rheumatological practice.
AB - To observe the actual laboratory screening for side effects of disease modifying
antirheumatic drugs (DMARDs) in daily rheumatological practice, a retrospective
multi-center cohort study was performed on the laboratory tests in DMARD treated
rheumatoid arthritis (RA) patients. RA patients were investigated by chart review
if they started with a DMARD (cohort 1) or were treated with a DMARD for at least
one year (cohort 2). Hematological, hepatic, and renal tests were collected. In
cohort 1 and 2, 513 and 1209 patients were included, respectively. A fairly
outlined screening profile was observed for each DMARD studied. Except for
antimalarials, the testing frequency decreased with time in cohort 1. For all
DMARDs the testing frequency in cohort 1 was higher than in cohort 2. In general,
rheumatologists requested laboratory tests less frequently than is
internationally recommended. This discrepancy raises questions about the relation
between the efficacy and costs of laboratory screening for side effects of DMARDs
in patients with RA.
PMID- 9645412
TI - Zopiclone as night medication in rheumatoid arthritis.
AB - Sleep disturbances and related daytime complaints are frequent in rheumatoid
arthritis (RA). The aim of the current study was therefore to evaluate the effect
of a newer hypnotic on sleep structure and clinical parameters in RA. Forty
outpatients were randomized to a two week treatment regimen with either 7.5 mg
zopiclone or placebo at bedtime. Clinical examinations were performed before and
after treatment and the degree of pain, fatigue, sleepiness, morning stiffness,
and activities of daily living were assessed. Two sleep questionnaires were also
completed weekly. Polysomnography was performed before the study and after 14
days of treatment. Recordings were evaluated using conventional sleep scoring as
well as frequency analysis of the electroencephalography (EEG). Patients in the
zopiclone group had subjective improvement of sleep, but otherwise no differences
in pain score or the other clinical parameters were found. Conventional sleep
assessments showed only minor changes during treatment, but frequency analysis
demonstrated a shift from the lower towards the higher EEG frequencies in the
active treatment group. Although the modulation of the EEG can represent a non
specific pharmacologic epiphenomenon, it might also reflect a disturbance of
sleep microstructure. In conclusion, treatment with zopiclone may be of value for
subjective sleep complaints in selected patients with RA, but it is doubtful
whether hypnotics improve daytime symptoms in this patient group.
PMID- 9645413
TI - Low incidence of osteoporosis in a two year follow-up of early community based
patients with rheumatoid arthritis.
AB - 52 patients with early rheumatoid arthritis (RA) were followed with regular
measurements of bone mineral density (BMD) and serum markers of type I collagen
metabolism in order to determine whether they develop osteoporosis during the
first two years of the disease course and if the changes in type I collagen
metabolites reflect the alterations in BMD. The mean percentage BMD change over
the first year of follow-up was -0.91 for lumbar spine (LS) and -0.76 for femoral
neck (FN); the corresponding figures from 0 to 24 months was -1.3 and -0.8,
respectively. During the follow-up, only five patients developed osteoporosis by
the Z-score definition (<-1). If defined by T-score (<-2.5) none of the patients
developed osteoporosis. The BMD change correlated neither with the clinical
parameters of disease activity nor with the markers of collagen metabolism.
However, the BMD change in FN was associated with the cumulative corticosteroid
dose (r=-0.31, p <0.05, 95% CI -0.54 to -0.04). Reasons for the lack of
accelerated bone loss in our series are open to various interpretations. This
series was community based and most of the patients had mild RA. The patients
were also actively treated and their physical function did not deteriorate.
PMID- 9645414
TI - Destruction and arthroplasties of the metatarsophalangeal joints in seropositive
rheumatoid arthritis. A 20-year follow-up study.
AB - Destruction and arthroplasties of the metatarsophalangeal (MTP)joints and
interphalangeal (IP) joint of the big toe were evaluated in 103 seropositive
rheumatoid arthritis (RA) patients in a prospective follow-up study at onset and
at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15
year follow-up and 68 attended the 20-year follow-up. Data on the forefoot
synovectomies and reconstructions performed were obtained from patient documents
and radiographs. The radiographs were assigned by the Larsen method; in the end
point analysis the last or preoperative radiograph was used. Erosions of Larsen
grade > or =2 were present in 6%/ of the investigated 1236 joints at onset and
after 20 years in 62%, respectively. At the end point, 24% of the joints were
severely damaged (Larsen grade 4-5). The MTP I and IP joints showed the lowest
grade of destruction during follow-up, and MTP V the worst destruction.
Synovectomies were performed in 24 MTP joints; a total of 75% of these joints
were later resected. MTP II-V head resections were performed in 21% and the
Keller procedure in 12% of the MTP I joints. Erosive changes occur early in the
MTP joints, and their grade of destruction is high; therefore they should be
included in radiographic criteria and scores. MTP synovectomies are insufficient
treatments for RA without concomitant immunosuppression of the disease.
PMID- 9645415
TI - Bone metabolism in patients with systemic lupus erythematosus. Effect of disease
activity and glucocorticoid treatment.
AB - The bone metabolism in patients with systemic lupus erythematosus (SLE) has
previously been examined, but the results are conflicting. In the present study
the bone mineral density (BMD) of the axial and the appendicular skeleton was
examined by means of dual energy x-ray absorptiometry. The bone turnover was
evaluated by means of biochemical markers in serum and urine in a prospective
cohort consisting of 36 female and male SLE patients. Repeated measurements of
BMD were performed for up to two years. The BMD was decreased in the hand and in
the femoral neck but normal in the spine and in the distal forearm. A weak
correlation was found between the BMD of the femoral neck and the total
consumption of glucocorticoids. Apart from this finding the BMD was uninfluenced
by treatment with glucocorticoids and cyclophosphamide. No significant changes of
BMD were found during the follow-up period. The serum concentration of the
carboxyterminal cross-linked telopeptide of type I collagen was increased in
almost all patients, but no other biochemical markers of bone metabolism were
abnormal.
PMID- 9645416
TI - Skeletal muscle immune deposits in systemic lupus erythematosus. Correlation with
histologic changes, autoantibodies, and clinical involvement.
AB - Skeletal muscle biopsy and autopsy samples of 132 SLE patients were studied by
immunofluorescence and light microscopic techniques. Immune deposits were
compared to histologic abnormalities and clinical and serologic findings. Immune
deposits with a mainly granular pattern were observed at different locations in
49 patients (37%). They correlated significantly (p<0.001) with inflammatory
myopathy, demonstrated in 33(25%), with noninflammatory myopathy which occurred
in 38 (29%) vasculitis, observed in 13(10%), and with noninflammatory
vasculopathy which was noted in 10 patients (8%). The correlation of muscle
immune deposits with anti-DNA antibodies was significant at p= 0.016. Anti-Sm and
anti-U1 RNP antibodies were associated significantly with the intensity of immune
deposits. Furthermore, a correlation of immune deposits with increased creatine
phosphokinase and myopathic electromyogram, but not with evidence of clinical
involvement, was shown. A key pathogenetic role of immune deposits in the
development of skeletal muscle histologic abnormalities in SLE was demonstrated.
PMID- 9645417
TI - Expression of the mucosal lymphocyte integrin alphaEbeta7 and its ligand E
cadherin in salivary glands of patients with Sjogren's syndrome.
AB - The expression of the mucosal lymphocyte integrin alphaEbeta7 and its ligand E
cadherin was analyzed in sialadenitic lesions of patients with Sjogren's syndrome
in order to assess the potential interactions between the mucosal and the
systemic immunological compartments. Immunohistochemical evaluation of the
inflammatory infiltrates in the salivary gland tissues in Sjogren's syndrome
patients revealed presence of alphaEbeta7-integrin-expressing lymphocytes, in 18
of 20 biopsies examined. The ligand for alphaEbeta7, E-cadherin was also found in
18 of 20 salivary gland biopsies analysed. These results suggest homing of
lymphocytes derived from the gut epithelium through the blood stream to inflamed
salivary gland tissue followed by in situ interaction with E-cadherin expressing
cells, the ligand for alphaEbeta7 expressing T lymphocytes.
PMID- 9645418
TI - Decreased Th1-like and increased Th2-like cells in systemic lupus erythematosus.
AB - The proportion of the lymphocytes which produce the cytokines corresponding to
murine T helper- (Th1) or Th2 cells was studied using flow cytometry in systemic
lupus erythematosus (SLE). When the peripheral mononuclear cells were stimulated
with phorbol myristate acetate and ionomycin in the presence of monensin, which
blocks the secretion of cytokines, the positive rates for the cytoplasmic IL-2
and IFN-gamma were lower and those for the cytoplasmic IL-4 and IL-10 were higher
in SLE than in normal subjects. When the cells were cultured with monensin alone,
the positive rates for these 4 cytokines were slightly increased in SLE. These
data suggest that the mononuclear cells are already activated in vivo and a
deviation of the proportion of the Th cells to the Th2-like ones might be
associated with the polyclonal B cell activation seen in SLE.
PMID- 9645419
TI - TAP2 alleles in inflammatory arthritis.
AB - Sixty patients with reactive arthritis (ReA) and 40 with rheumatoid arthritis
(RA), were typed for H LA-B27 and class II antigens DR and DQ, and studied for
TAP2 gene polymorphism in comparison with 60 healthy controls. TAP2 polymorphisms
at positions 379, 565, 665, and 687 were analyzed using amplification refractory
system-based PCR and polymorphisms at positions 386 and 651 using oligonucleotide
hybridization. The frequency of the TAP2A/A genotype was 30%(12/40) in RA, in
contrast to 13% (8/60) in the controls. This genotype was further associated with
DRB1*04 positive RA (10/24, 42%, P=0.01), as well as the TAP2A allele (31/48,
65%, P =0.012). Thr/Thr dimorphism at TAP2 position 665 (24/40, 60%, P=0.024) and
Stop/Stop dimorphism at TAP2 position 687 (24/40, 60%, P=0.024) were found to be
increased in RA patients as compared to controls. When TAP2I/J polymorphism was
studied, TAP2J positivity was found associated with the HLA-B27DR4-DQB1*0301
haplotype in ReA patients. 9/12 of these were positive as compared to 20/60 in
random controls (P=0.010). Polymorphisms of the TAP2 gene were found to be
associated with subgroups of RA and ReA patients with disease associated markers
(e.g. TAP2A in DRB1*04 positive RA, or TAP2J in HLA-B27-DRB1*04-DQB1*0301
positive ReA). These may thus serve as additional markers of specific haplotypes
associated with susceptibility to inflammatory arthritis.
PMID- 9645420
TI - Churg-Strauss syndrome presenting with pulmonary capillaritis and diffuse
alveolar hemorrhage.
AB - Churg-Strauss syndrome (CSS) is a rare disorder characterized by the
histopathological triad of systemic necrotizing vasculitis, extravascular
granuloma, and eosinophilic infiltrate, occurring in individuals with asthma or a
history of allergy. We report a case of CSS with rare presentation of diffuse
pulmonary hemorrhage. A transbronchial lung biopsy showed necrotizing vasculitis,
pulmonary capillaritis, and prominent eosinophilic infiltrate. At autopsy,
necrotizing granuloma and diffuse alveolar hemorrhage were found in the lungs.
Laboratory data showed hypereosinophilia, disseminated intravascular
coagulopathy, and positive anti-proteinase 3 antineutrophil cytoplasmic antibody
(ANCA). This case emphasize that CSS should be considered in the differential
diagnosis of ANCA-positive vasculitis with diffuse alveolar hemorrhage.
PMID- 9645421
TI - Henoch-Schoenlein purpura and acute interstitial nephritis after intravenous
vancomycin administration in a patient with a staphylococcal infection.
AB - We describe a case of Henoch-Schoenlein purpura, associated with oliguric acute
renal failure due to acute interstitial nephritis histologically proven, in a
patient with a staphylococcal chest infection. The clinical syndrome appeared
twice after vancomycin administration and yielded on the withdrawal of the drug.
As pathogenetic mechanism we propose an anaphylactoid reaction either to
vancomycin or to a staphylococcal glycoprotein released after breakdown of the
microbial cells caused by vancomycin.
PMID- 9645422
TI - Peripheral beta-endorphin in rheumatoid arthritis.
PMID- 9645423
TI - Cricoarytenoiditis in systemic lupus erythematosus.
PMID- 9645424
TI - Cyclin-specific START events and the G1-phase specificity of arrest by mating
factor in budding yeast.
AB - The START cell cycle transition in the budding yeast Saccharomyces cerevisiae is
catalyzed by the Cdc28 cyclin-dependent kinase associated with Cln-type cyclins.
Since ectopic expression of the B-type cyclin CLB5 can efficiently rescue the
inviability that results from CLN depletion, we tested the specificity of the CLN
and CLB classes of cyclins for promoting START-associated events. Several aspects
of the regulation of the mating factor response were compared for cells in which
START activity was provided by either Cln-cyclins or Clb5. Unlike Cln1 and Cln2,
high level expression of Clb5 was unable to repress the activity of the mating
factor response pathway at START. Downregulation of Far1 protein at START is
normal in cln- GAL1::CLB5 cells. Even though the Clb5-Cdc28 kinase activity in
cln- GAL1::CLB5 cells is not downregulated in response to mating factor, cells
arrest in the first cycle after addition of mating factor with a similar
sensitivity as wild-type cells. However, whereas wild-type cells treated with
mating factor arrest specifically in G1 phase as unbudded cells with unreplicated
DNA (pre-START), most cln- GAL1::CLB5 cells arrest as budded post-START cells
with replicated DNA. Our findings demonstrate the ability of post-START cells to
arrest in response to mating factor and provide novel evidence for mechanisms
that contribute to restrict mating factor-induced arrest in wild-type cells to
the G1 phase of the cell cycle.
PMID- 9645425
TI - Genes for the ribosomal S4 protein encoded in higher plant mitochondria are
transcribed, edited, and translated.
AB - Here we describe the structure and expression of the mitochondrial gene that
encodes the S4 subunit of the mitochondrial ribosome (rps4) in two higher plants,
rapeseed and rice. The ORFs of rapeseed and rice rps4 genes are 362 and 352
codons long, respectively, and their corresponding transcripts are edited (C-to-U
conversions) in 19 and 15 positions, respectively. The amino acid sequences
deduced from the sequences of the two rps4 genes are 78.1% identical to each
other and show about 50% identity to the liverwort (Marchantia polymorpha)
mitochondrial RPS4 polypeptide. Both higher plant mitochondrial genes have an
inserted sequence (of 137 and 141 codons for rapeseed and rice, respectively)
relative to the liverwort rps4 gene. In rice rps4, the 3' portion of the inserted
sequence can potentially form two stem-loop structures that resemble two domains
characteristic of group II introns, i.e., domains V and VI. However, RT-PCR
analysis showed that these sequences were not spliced out during maturation of
the rps4 transcripts. Antibodies specific for the plant RPS4 proteins were
prepared. Protein blot analysis revealed that RPS4 polypeptides are present in
both rapeseed and rice mitochondria, whose sizes are in agreement with the
molecular weights calculated from the non-spliced sequences. The rps4 genes and
RPS4 polypeptides have been also identified in the mitochondria of wheat, maize,
soybean, and turnip by Southern and Western analyses, respectively.
PMID- 9645426
TI - Characterization of a 7S globulin-deficient mutant of soybean (Glycine max (L.)
Merrill).
AB - We attempted to characterize a soybean mutant lacking the 7S globulin (beta
conglycinin) subunits, alpha, alpha' and beta. The results of Southern and
northern blot analyses indicated that the deficiency is not caused by a lack of,
or structural defects in, the 7S globulin subunit genes, but rather arises at the
mRNA level. Despite the independent inheritance of the two loci containing the
alpha-and alpha'-subunit genes and the organization of the multi-gene families
encoding these subunits and the beta-subunit, a single recessive gene controls
the null trait of the mutant. This, taken together with the above results, leads
to the assumption that the mutant gene encodes a common factor that regulates the
7S globulin subunit genes. Transient expression of glucuronidase from the
promoters of the alpha'- and beta-subunit genes was detected in the mutant
cotyledons. The results of gel mobility shift assays using the 5'-flanking
regions of the alpha'- and beta-subunit genes failed to detect a deficiency of
nuclear factors interacting with these regions. We propose that a seed-specific
mechanism of expression of 7S globulin genes might be involved in chromatin
organization, and that such an organization might not work normally in the
mutant. The possibility that transcript stability is lowered in the mutant is not
excluded.
PMID- 9645427
TI - Expression of the yeast BFR2 gene is regulated at the transcriptional level and
through degradation of its product.
AB - The essential Saccharomyces cerevisiae gene BFR2 has been isolated as a high-copy
suppressor of the growth defects induced by Brefeldin A, a drug that disrupts the
Golgi apparatus and its protein influx. Furthermore, BFR2 has been found to
display genetic interactions with four mutations affecting protein transport to
the Golgi apparatus. Here we show that the level of BFR2 mRNA rapidly increased
over fivefold in response to cold shock, and over threefold following nutrient
replenishment by dilution of cells from exhausted to fresh minimal medium. During
subsequent growth, the transcript level returned to its basal values, except for
a transient drop toward the end of the exponential phase. The early burst of
transcription was not caused by toxic compounds in the fresh medium, or by
synchrony among cells that had simultaneously entered their first cell cycle. The
BFR2 gene product (Bfr2p) was synthesized following the early burst of mRNA, and
was no longer produced when the mRNA was back to basal level. Bfr2p was finally
degraded after growth became limited, and reached undetectable levels in
exhausted medium. Under steady-state conditions of lengthened exponential phase,
the intracellular level of Bfr2p remained constant. This peculiar pattern of gene
expression suggests that Bfr2p is essential for mass growth or cell
proliferation, whereas it is either toxic or not required during nutrient-limited
growth.
PMID- 9645428
TI - Genetic rearrangements in the pathogenicity locus of Clostridium difficile strain
8864--implications for transcription, expression and enzymatic activity of toxins
A and B.
AB - The pathogenicity locus (PaLoc) of Clostridium difficile isolate 8864 was
investigated to locate genetic rearrangements that would explain the exceptional
pathogenicity of this particular isolate. Two major changes were defined: an
insertion of 1.1 kb between the two genes tcdA and tcdE, coding for the
enterotoxin and an accessory protein of unknown function, respectively, and a
deletion of 5.9 kb encompassing the 3' ends of tcdA and tcdC. Transcription of
the tcdA-E genes is severely affected by both rearrangements, explaining the
demonstrated complete lack of TcdA polypeptide. We present a model of coordinate,
growth-related transcription of the tcdA-E genes that confirms our previous
findings in strain 10463. Recombinant TcdA-8864 had UDP-glucose
glucosyltransferase activity, proving that the N-terminal 698 amino acids of the
polypeptide represent the catalytic domain. However, this truncated TcdA molecule
lacks a ligand and translocation domain. To assess the catalytic domain of TcdB
8864, the sequence of the 5' end of its gene was determined. TcdB-8864 shows high
homology to TcdB-1470 but lower homology to TcdB-10463 within this domain. This
fits well with the altered glucosylation specificity of TcdB-8864 (Rac1, Rap2 and
Ra1). Having defined the variations of transcription, expression and enzymatic
activity of toxins A and B, implications for the pathogenic potential of strain
8864 are discussed.
PMID- 9645429
TI - A single human cell expresses all messenger ribonucleic acids: the arrow of time
in a cell.
AB - Expression of 25 mRNAs in a single human lymphocyte was investigated using the
reverse transcription nested polymerase chain reaction (RT nested PCR) method.
Proteins corresponding to the mRNA investigated were mucin antigen, melanoma
antigen, pregnancy-specific beta-1 glycoprotein 4, phenylethanolamine-N-methyl
transferase, beta B3-crystallin, homeobox 4A, interleukin 2, cluster of
differentiation 8, progesterone receptor, parathyroid hormone, gastrin,
cholecystokinin/pancreozymin, glucagon, insulin, enkephalin, thyroid stimulating
hormone, adrenocorticotropic hormone, synapsin I, immunoglobulin (Ig)M, IgD,
IgG1, IgG3, IgE, IgA, and T cell receptor alpha. All mRNAs were detected in
single lymphocytes of two individuals, without exception. In addition,
transcripts of IgM, IgD, IgG1, IgG3, IgE, IgA, and the T cell receptor a gene
were detected in single sperms. The results strongly suggest the possibility that
all mRNAs may be expressed in a single human cell, of both somatic and germ
lineage. Thus, cells can consume energy in vain to produce functionally
meaningless gene transcripts. However, this basal or illegitimate transcription
may be essential for the birth of living matter: the arrow of time in a cell.
Moreover, the phenomenon implies the potential of using lymphocytes in place of
inaccessible tissue for the diagnosis of genetic diseases.
PMID- 9645430
TI - Genetic analysis of an essential cytoplasmic domain of Escherichia coli SecY
based on resistance to Syd, a SecY-interacting protein.
AB - We previously described a dominant negative secY-d1 allele in Escherichia coli,
whose product interferes with protein export, presumably by sequestering SecE,
the stabilizing partner of SecY. Syd is the product of a multicopy suppressor of
the secY-d1 phenotype, and its overproduction preferentially stabilizes the wild
type SecY protein. In contrast, overproduction of Syd is toxic to the secY24
mutant, which shows a partial defect in SecY-SecE interaction. We isolated Syd
resistant revertants from the secY24 mutant. Pseudo-reversions mapped to sites at
or near the secY24 mutation site (Gly240-->Asp). The secY249 mutation (Ala249-
>Val) intragenically suppressed Syd sensitivity, but not the temperature
sensitive Sec phenotype of the secY24 mutation. The SecY249 mutant protein shows
a reduced capacity to be stabilized by Syd, suggesting that the mutation weakens
the SecY-Syd interaction. The other two mutations changed residue 240 (the site
of the secY24 alteration) to Asn (secY245) or Ala (secY241) and restored the
ability of the cell to export protein. Although the secY245 mutant retained some
sensitivity to Syd overproduction, the secY241 mutant was completely Syd
resistant. Furthermore, the secY241 mutation seemed to represent a "hyper
reversion" with respect to the SecY-SecE interaction. Protein export in this
mutant was no longer sensitive to SecY-d1. When the secY-d1 mutation was combined
intragenically with secY241, the resulting double mutant gene (secY-d1-241)
showed an increased ability to interfere with protein export. On the basis of our
model for SecY-d1, these results suggest that the secY241 alteration enhances
SecY-SecE interaction. These results indicate that residue 240 of SecY is crucial
for the interaction between the cytosolic domains of SecY and SecE required for
the establishment of the translocase complex.
PMID- 9645431
TI - Characterization of ptxS, a Pseudomonas aeruginosa gene which interferes with the
effect of the exotoxin A positive regulatory gene, ptxR.
AB - The complicated process of exotoxin A production by Pseudomonas aeruginosa is
controlled by several genes. We have recently described a toxA positive
regulatory gene, ptxR. We also proposed the presence of another gene which is
adjacent to ptxR and interferes with ptxR function on exotoxin A production. In
the presence of a fragment that carries the putative gene, the enhancement in
exotoxin A production by ptxR was reduced threefold. In this study, we describe
the characterization of this gene. Nucleotide sequence analysis of the 2.1-kbp
fragment at the 5' end of ptxR revealed the presence of an open reading frame
designated ptxS (the gene next to ptxR) which encodes a 37.4-kDa protein. The
gene ptxS is transcribed in the opposite orientation to ptxR from the other DNA
strand. The deduced amino acid sequence of ptxS exhibited a strong homology to
several proteins of the GalR-LacI family of repressors. A putative helix-turn
helix DNA binding motif was identified at the amino-terminus region of PtxS. When
PtxS was overexpressed in Escherichia coli using the T7 expression system, a
single protein of 38-kDa molecular weight was detected. An isogenic mutant
defective in ptxS was constructed in PAO1 using the gene replacement technique.
The loss of ptxS resulted in a twofold increase in exotoxin A production compared
to PAO1. The effect of ptxS on ptxR was examined using a ptxR-lacZ fusion. In the
presence of ptxS, the level of beta-galactosidase activity produced by the ptxR
lacZ fusion was significantly reduced. These results suggest that ptxS encodes a
protein which negatively regulates ptxR expression in P. aeruginosa.
PMID- 9645432
TI - Inheritance and usefulness of AFLP markers in channel catfish (Ictalurus
punctatus), blue catfish (I. furcatus), and their F1, F2, and backcross hybrids.
AB - Eight primer combinations were used to investigate the application of amplified
fragment length polymorphism (AFLP) markers in catfish for genetic analysis.
Intraspecific polymorphism was low among channel catfish or blue catfish strains.
Interspecific AFLP polymorphism was high between the channel catfish and blue
catfish. Each primer combination generated from 70 to more than 200 bands, of
which 38.6 75.7% were polymorphic between channel catfish and blue catfish. On
average, more than 20 polymorphic bands per primer combination were produced as
quality markers suitable for genetic analysis. All AFLP markers were transmitted
into channel catfish x blue catfish F1 hybrids, except rare markers that were
heterozygous in the parents and therefore were segregating in F1 hybrids. The two
reciprocal channel catfish x blue catfish F1 hybrids (channel catfish female x
blue catfish male; blue catfish female x channel catfish male) produced identical
AFLP profiles. The AFLP markers were inherited and segregated in expected
Mendelian ratios. At two loci, E8-b9 and E8-b2, markers were found at
significantly lower frequencies than expected with F2 and backcross hybrids which
had been selected for increased growth rates. The reproducibility of AFLP was
excellent. These characteristics of the catfish AFLP markers make them highly
useful for genetic analysis of catfish, especially for construction of genetic
linkage and quantitative trait loci maps, and for marker-assisted selection.
PMID- 9645433
TI - HSF3, a new heat shock factor from Arabidopsis thaliana, derepresses the heat
shock response and confers thermotolerance when overexpressed in transgenic
plants.
AB - Organisms synthesize heat shock proteins (HSPs) in response to sublethal heat
stress and concomitantly acquire increased tolerance against a subsequent,
otherwise lethal, heat shock. Heat shock factor (HSF) is essential for the
transcription of many HSP genes. We report the isolation of two HSF genes, HSF3
and HSF4, from an Arabidopsis cDNA library. Transgenic Arabidopsis plants were
generated containing constructs that allow expression of HSF3 and HSF4 or the
respective translational beta-glucuronidase (GUS) fusions. Overexpression of HSF3
or HSF3-GUS, but not of HSF4 or HSF4-GUS, causes HSP synthesis at the non-heat
shock temperature of 25 degrees C in transgenic Arabidopsis. In transgenic plants
bearing HSF3/HSF3-GUS, transcription of several heat shock genes is derepressed.
Electrophoretic mobility shift assays suggest that derepression of the heat shock
response is mediated by HSF3/HSF3-GUS functioning as transcription factor.
HSF3/HSF3-GUS-overexpressing Arabidopsis plants show an increase in basal
thermotolerance, indicating the importance of HSFs and HSF-regulated genes as
determinants of thermoprotective processes. Plants transgenic for HSF3/HSF3-GUS
exhibit no other obvious phenotypic alterations. Derepression of HSF activity
upon overexpression suggests the titration of a negative regulator of HSF3 or an
intrinsic constitutive activity of HSF3. We assume that stable overexpression of
HSFs may be applied to other organisms as a means of derepressing the heat shock
response.
PMID- 9645434
TI - Alteration of the largest subunit of RNA polymerase II and its effect on
chromosome stability in Schizosaccharomyces pombe.
AB - A mutation in the RNA polymerase II largest subunit (RpII LS) that is related to
abnormal induction of sister chromatid exchange has previously been described the
CHO-K1 cell mutant tsTM4. To elucidate the molecular basis of this effect we
introduced the mutation into the homologous site in the Schizosaccharomyces pombe
rpbl gene, which encodes RpII LS. Since the tsTM4 mutant exhibited a decrease in
the rate of DNA synthesis in cells arrested in S phase at the nonpermissive
temperature, we focussed on the study of growth, the cell cycle, and chromosome
stability at various temperatures. First, we examined the effects of the mutation
on haploid yeast cells. The mutant showed slower growth than the wild type, but
cell growth was not arrested at the nonpermissive temperature. When growing cells
were shifted to the nonpermissive temperature, an accumulation of cells in G1
and/or G0 was observed. Tetrad analysis suggested that these phenotypes were
associated with the mutation. In diploid cells, chromosome instability was
detected by loss of intragenic complementation between two alleles of the ade6
gene. An abnormal fraction of cells containing an intermediate DNA content was
also observed by FACS analysis. The accumulation of this fraction may reflect the
fact that a large number of cells are in S phase or have an abnormal DNA content
as a result of chromosome instability. These observations demonstrate that the S.
pombe rpb1 mutant exhibits a phenotype very similar to that of the CHO-K1 cell
mutant tsTM4.
PMID- 9645435
TI - Identification and characterisation of an RPD3 homologue from maize (Zea mays L.)
that is able to complement an rpd3 null mutant of Saccharomyces cerevisiae.
AB - In mammals, yeast and Drosophila, the histone deacetylase RPD3 proteins can alter
the expression of genes involved in fundamental biological processes by affecting
the degree of acetylation of histones and changing chromatin structure. Here we
report the isolation of a cDNA sequence encoding an RPD3 homologue from maize,
which is able to complement the phenotype of an rpd3 null mutant of the yeast
Saccharomyces cerevisiae. The expression of the corresponding gene(s) was
assessed in different maize tissues. The number of homologous loci was estimated
by Southern hybridisation to be in the range of two to three, and the chromosomal
location of one of these loci was determined. Phylogenetic analysis and tests for
relative divergence rates, using related RPD3 sequences from different species,
were performed, and suggest that different polymorphic forms of RPD3-like
proteins that evolve at distinct rates are present in the species considered.
PMID- 9645436
TI - Integration host factor affects the oxygen-regulated expression of photosynthesis
genes in Rhodobacter capsulatus.
AB - The puf and puc operons of Rhodobacter capsulatus, which encode pigment binding
proteins, are regulated by oxygen tension. Strain IR4 which carries a point
mutation in the himA gene for integration host factor (IHF) shows a delayed
increase in the amount of photosynthetic complexes after reduction of oxygen
tension when compared to the isogenic wild-type strain. This delay in the
formation of photosynthetic complexes correlates with a delay in increasing the
level of transcription of the puf and puc operons, whereas the transcription of
the bchD genes is not affected by IHF. Several IHF binding sites can be
identified upstream of the puf and puc transcriptional starts by in vitro
footprint analysis. Our results suggest that IHF facilitates the binding of other
trans-acting factors, e.g. RegA, which in turn stimulate transcription of the puf
and puc genes under low oxygen tension.
PMID- 9645437
TI - Analysis of the Ac promoter: structure and regulation.
AB - The Ac-encoded transposase, a factor that is essential for the mobility of the Ac
element, is expressed under the control of a promoter that lacks a conventional
TATA box. The regulation of this promoter is poorly understood. We have analyzed
Ac promoter structure and activity, both in vitro and in vivo, using transgenic
tobacco plants and cell suspensions. A deletion analysis of the Ac 5' region
showed that the minimal promoter is located within 70 bp of the major
transcription initiation site (at position 334). The minimal promoter includes
the sequence TAAGAAATA at position 294 303, i.e., about 30 nucleotides upstream
from the transcription start site. This sequence binds specifically to the TATA
binding protein (TBP), suggesting that it is functional as a TATA box. The
regulation of the Ac promoter was studied throughout plant development. Levels of
Ac mRNA were low in all tissues studied, with higher expression being observed in
dividing cells. In order to test whether Ac promoter is regulated during the cell
cycle, a tobacco cell suspension transformed with Ac, was grown synchronously. No
differences were found in Ac mRNA levels between cells in S, G2, M, or G1 phases;
however, expression was lower in the stationary phase. We conclude that Ac
promoter is not cell-cycle regulated but is expressed at a higher level in
dividing cells. The possible relationship between promoter features and the
regulation of Ac element transposition is discussed.
PMID- 9645438
TI - Genetic aspects of prostate cancer.
AB - Despite its high incidence and mortality rate, the molecular mechanisms
underlying the oncogenesis and progression of prostate cancer are still unclear.
This review, based on recently published data, surveys the current state of
knowledge of human prostate oncogenesis, dealing with genetic predisposition in
familial clusters of prostate cancer, providing new information on the somatic
genetic alterations, which have been approached in four ways (measurement of DNA
content, cytogenetic analysis, in situ hybridization, and molecular analysis),
and investigating the problems of androgen independence and intratumour
heterogeneity in prostate tumours. Lastly, the potential clinical applications of
the genetic alterations, which may become important in the near future, are
addressed.
PMID- 9645439
TI - Mitogen-activated protein kinases and apoptosis in PIN.
AB - Mitogen-activated protein (MAP) kinases are key elements of the signalling
systems needed to transduce different extracellular messages into cellular
responses. At least three parallel MAP kinase pathways have been identified: one,
stimulated by serum and growth factors to activate extracellular signal-regulated
protein kinases (ERKs) by dual tyrosine and threonine phosphorylation, triggers
cell proliferation or differentiation; the other two, induced by a variety of
cellular stresses to activate c-jun N-terminal kinases (JNKs) and reactivating
kinase (p38/RK), result in growth arrest and induction of apoptosis. Mitogen
activated protein kinase phosphatases (MKPs) inactivate MAP kinases through
dephosphorylation and, thus, can modulate the MAP kinase pathways. Expression of
JNK-1, ERK-1, p38/RK and MKP-1 proteins was investigated by immunohistochemistry
and expression of MKP-1 mRNA by in situ hybridisation in 50 cases of high-grade
prostatic intraepithelial neoplasia (PIN), thought to represent the precursor of
prostate cancer. The frequency of apoptotic cells was also determined in these
cases. Overexpression of the three MAP kinases and MKP-1 mRNA was found in all
cases of high-grade PIN compared with normal prostate. Immunoreactivity for MKP-1
protein was found to be as intense as in normal glands in 30% and weaker in 56%
of the PIN cases. Fourteen per cent of PIN cases did not stain with MKP-1
antibody. The proportion of apoptosis was significantly higher (P < 0.008) in PIN
lesions that did not express MKP-1 protein than in those that did. These results
are consistent with our previous demonstration of preferential inhibition of the
apoptosis-related kinases by MKP-1 and further support the contention that MKP-1,
even in PIN, may shift the balance existing between cell proliferation and death.
When expressed, it may inhibiting those pathways that lead to apoptosis.
PMID- 9645440
TI - Apoptosis in human colorectal tumours: ultrastructure and quantitative studies on
tissue localization and association with bak expression.
AB - Apoptotic cell death in human tumours has been demonstrated by electron and light
microscopy. In adenomas, fragmented and apoptotic nuclei and signs of
phagocytosis have been observed close to the basement membrane. In carcinomas the
characteristic structures were apoptotic bodies with small fragments of
chromatin. DNA fragmentation was shown by in situ end-labelling. Quantitative
assessment of apoptosis and proliferation revealed a high apoptotic index (AI) in
all types of adenoma (tubular: 1.77+/-0.35%, tubulovillous: 2.38+/-0.41%;
villous: 3.3+/-0.39%) as well as loss of compartmentalization of proliferating
and dying cells. In carcinomas a shift towards proliferation was evident, as
shown by lower AIs than in adenomas (0.9+/-0.68% and 1.1+/-0.12% for moderately
and poorly differentiated tumours), higher Ki67 indices (38.32+/-2.23% and 57+/
3.89%, respectively) and higher mitosis (0.9+/-0.56% and 1.21+/-0.17%,
respectively). However, apoptosis was observed in all tumours and is available as
a target for therapeutic intervention. Expression of the apoptosis related
proteins bcl-2 and bak also reflected loss of compartmentalization. While bcl-2
did not show a consistent relationship to AI in tumour specimens, bak was
positively correlated with apoptosis in 4 of 8 adenomas and 4 of 7 carcinomas,
suggesting a role for this protein in the induction of apoptosis in a subset of
tumours.
PMID- 9645441
TI - CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of
papillary thyroid carcinoma.
AB - CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several
lineages. It is present on multipotential neuroepithelial cells during
embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin
also express CD57. Its role in the diagnosis of thyroid tumours is controversial.
We have studied CD57 expression by immunohistochemistry to determine its utility
in the classification of thyroid follicular lesions. Study material included 114
normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22
follicular adenomas, 20 cases of Hashimoto's thyroiditis and 6 of Grave's
disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary
carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of
follicular adenomas and 10% of colloid nodules. It was not expressed in the
normal thyroid. CD57 expression in thyroid carcinomas was significantly different
from that in normal and benign thyroid lesions (P < 0.0001). The follicular
variant of papillary thyroid carcinoma also showed significantly higher CD57
expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009).
No significant difference was seen between colloid nodules and follicular
adenomas. We conclude that CD57 immunohistochemistry is valuable in the
classification of thyroid follicular lesions into benign and malignant groups and
is also helpful in the diagnosis of the follicular variant of papillary thyroid
carcinoma.
PMID- 9645442
TI - Mammary foam cells. Characterization by immunohistochemistry and in situ
hybridization.
AB - Cells showing abundant, finely vacuolized cytoplasm (foam cells) are found
frequently in most benign lesions of the breast and in certain malignant breast
tumours. The origin of mammary foam cells (FCs) has not been clarified, and we
therefore studied the morphological features of mammary FCs in a series of 50
benign lesions. The FCs were subdivided, on the basis of their distribution into
FCs lining the glandular lumina, intraluminal FCs, intraepithelial-pagetoid FCs,
and stromal FCs. The lesions were tested with a panel of antibodies against
macrophage (MAC 387, CD68) and epithelial (epithelial membrane antigen [EMA],
gross cystic disease fluid protein 15 [GCDFP15] and cytokeratin) markers. The
lesions were examined for the presence of PIP/GCDFP15-specific mRNA by an in situ
hybridization technique. Three different types of FCs were identified. Type A FCs
are epithelial cells (positivity with EMA and cytokeratin) and show apocrine
differentiation (positivity with GCDFP15 antiserum and expression of PIP/GCDFP15
mRNA). Type B FCs are of macrophage origin, as they are positive with the
macrophage markers and lack cytokeratin and PIP/GCDFP15 mRNA. Finally, type C FCs
show an intermediate profile between an epithelial cell and a macrophage: they
are both CD68 and GCDFP15 positive and show a thin peripheral rim of positivity
with anti-cytokeratin antibody. They lack PIP/GCDFP15 mRNA. Our results indicate
the possibility of a spectrum of phenotypes in mammary FCs, from epithelial
apocrine cells to macrophage-derived phagocytic cells.
PMID- 9645443
TI - Bcl-2 protein and prognosis in patients with potentially curable non-small-cell
lung cancer.
AB - The bcl-2 proto-oncogene functions as a cell death suppressor, and its expression
prolongs cell survival by blocking apoptosis. Data available on the clinical
relevance of bcl-2 protein expression in patients with non-small-cell lung cancer
(NSCLC) are controversial. We analysed the role of bcl-2 protein expression on 6
year relapse-free survival in 229 patients with stage I-IIIa NSCLC (101 squamous
cell carcinomas and 128 adenocarcinomas) subjected to surgery, with curative
intent. Immunohistochemical analysis was performed on archival material by using
a monoclonal antibody anti-bcl-2 (clone 124). Bcl-2 protein expression, which was
detected in 22% of the cases, was significantly related to stage, histology and
grading, and was an indicator of clinical outcome. The probability of relapse
free survival at 6 years was longer for patients with bcl-2-positive tumours
(74%) than for those with bcl-2-negative tumours (57%) (P=0.02). This finding was
mainly evident for the subgroups of patients with stage IIIa tumours (P=0.05),
squamous cell carcinoma (P=0.03) or moderately/poorly differentiated tumours
(P=0.02). However, multivariate analysis by Weibull's regression model indicated
that bcl-2 protein expression was not an independent prognostic risk factor in
patients with curable NSCLC when the information provided by stage was available.
PMID- 9645444
TI - Expression of bcl-2 oncoprotein in transitional cell carcinoma of the upper
urinary tract.
AB - We investigated the immunoreactivity for bcl-2 oncoprotein in 154 cases of
transitional cell carcinoma of the upper urinary tract (TCC-UUT) and its relation
with the immunoreactivity for p53 oncoprotein and proliferating cell nuclear
antigen (PCNA) immunoreactivity. Immunohistochemically, bcl-2 oncoprotein was
recognized as positive in 29.2% of the samples. The immunoreactivity for bcl-2
oncoprotein was significantly (P < 0.05) correlated only with stage, though there
was a borderline correlation (P = 0.050) with PCNA immunoreactivity. Furthermore,
in invasive TCC the immunoreactivity for bcl-2 oncoprotein was associated with
PCNA immunoreactivity (P < 0.041). The 5-year disease-free and overall survival
rates were 55.7% and 71.5%, respectively. A univariate analysis of survival
revealed that stage, grade, pattern of growth, immunoreactivity for p53
oncoprotein, and PCNA immunoreactivity each had a significant effect on disease
free and overall survival rates, whereas the immunoreactivity for bcl-2
oncoprotein had no significant effect on either rate. In the final models of the
multivariate analysis, stage was found to be the only prognostic factor for
disease-free survival and for overall survival. Detection of immunoreactivity for
bcl-2 oncoprotein appears to be of no real value in deciding the prognosis of TCC
UUT.
PMID- 9645445
TI - Ovarian-like stroma in an invasive mucinous cystadenocarcinoma of the pancreas
positive for inhibin. A hint concerning its possible histogenesis.
AB - A female patient with a mucinous cystadenocarcinoma originating from a mucinous
cystadenoma of the pancreas is presented. The cystic tumour was diagnosed 3 years
before and was treated with interventional external and internal surgical
drainage before radical resection was accomplished by left hemipancreatectomy.
Histology showed simultaneous occurrence of mildly dysplastic and invasive
malignant epithelium. Immunohistology revealed inhibin-positive cells in the
ovarianlike stroma of the tumour. The demonstration of ovarian-like stroma
positive for inhibin suggests that this could be a hamartoma with dispersed sex
cord stroma, which would explain the predominance of the female gender in
mucinous cystic tumours of the pancreas.
PMID- 9645446
TI - Bleomycin-induced pulmonary fibrosis in rat is associated with increased
expression of collagen-binding heat shock protein (HSP) 47.
AB - Increased accumulation of collagens in extracellular matrix (ECM) is mainly
responsible for bleomycin-induced pulmonary fibrosis in rats. This study was
designed to assess whether increased collagen accumulation in bleomycin-induced
pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular
chaperone for collagen biosynthesis. We investigated the expression of type I and
type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen
male Wistar rats were divided into two groups; group I: bleomycin-induced
pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary
fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg
body weight) intratracheally. Three bleomycin-treated rats and two age-matched
control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of
the experiment. In bleomycin-treated rats, histological examination revealed
pulmonary fibrosis, which increased with time. Increased type I and type III
collagen desposition was observed in the lungs of all the bleomycin-treated rats.
Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong
immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In
addition, increased numbers of phenotypically altered myofibroblasts (alpha
smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were
seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of
collagens and their molecular chaperone HSP47 expression was found in the
bleomycin-treated lungs, and their co-localization could be detected by double
immunostaining. Overexpression of HSP47 may play a significant part in the
excessive assembly of collagens and could contribute in this way to the fibrosis
found in bleomycin-treated rat lungs.
PMID- 9645447
TI - Spontaneous myocarditis in DBA/2 mice. Light microscopic study with transmission
and X-ray analytical electron microscopic studies.
AB - DBA/2 inbred mice spontaneously develop myocarditis and a unique form of
subepicardial inflammation of the right ventricle characterized by a prominent
eosinophilic infiltrate with calcinosis. We studied this myocarditis using light
microscopy and both transmission and analytical X-ray electron microscopy, paying
particular attention to eosinophil-associated cardiocyte injury. At 5 weeks of
age, many eosinophils and mononuclear cells (MNCs) were seen in the subepicardium
of the right ventricle. Electron microscopy showed that cardiocytes underwent
degenerative changes, including myofibrillar lysis, accumulation of Z-band
material and mitochondrial inclusions, and rupture of plasma membranes. The
infiltrating eosinophils appeared to be activated, and cells with cytoplasmic
vacuoles, suggestive of degranulation, were noted. The myocardial injury was most
severe in the 7th week and healed with myocardial fibrosis and calcinosis by the
8th week. Analytical X-ray electron microscopy showed that the calcinosis was
initiated in mitochondrial inclusions of injured cardiocytes. The peripheral
eosinophil count did not increase during the course of the disease, but there was
a positive correlation between the ratio of eosinophils to infiltrated white
blood cells (Eo/WBCs) in the right ventricle and the severity of myocardial
damage. Eosinophils may play a significant part in subepicardial cardiocyte
injury seen in DBA/2 mice.
PMID- 9645448
TI - Pancreatic leiomyosarcoma. Case report with immunohistochemical and flow
cytometric studies.
AB - A leiomyosarcoma originating from the pancreas of a 57-year-old man is presented.
A 6x5x4 cm tumour was located in the head region, and the patient underwent
surgical palliation. Immunohistochemical studies excluded an epithelial origin; a
myogenic origin was suggested by strong vimentin and smooth muscle actin
positivity. Flow cytometric analysis revealed an aneuploid pattern (DNA index:
1,561). The patient died with widespread metastases 7 month after the operation.
PMID- 9645449
TI - Coexisting primary early gastric plasmacytoma and sarcoidosis with
hypercalcaemia.
AB - We report on a 61-year-old woman with coexisting early stage primary gastric
plasmacytoma and sarcoidosis with hypercalcaemia. Laboratory data on admission
showed hypercalcaemia, with 12.8 mg/dl, parathyroid hormone-related peptide
(PTHrP) 1.2 pmol/l, C-PTHrP 69.5 pmol/l, and 1,25-dihydroxyvitamin D3 46.7 pg/ml.
Neoplastic plasma cells proliferated in the propria mucosa of the stomach, showed
a monoclonal immunoglobulin of cytoplasmic IgA (lambda light chain) and were
positive for leucocyte common antigen and epithelial membrane antigen on paraffin
section prepared from a stomach biopsy specimen. Russel bodies were present, as
were crystals. Abundant sarcoid granulomas were observed in many of the regional
lymph nodes around the stomach and in the dermis of a skin nodule. The patient
underwent subtotal gastrectomy with administration of antimyeloma chemotherapy.
We suggest that the hypercalcaemia in this patient was due to PTHrP production by
neoplastic plasma cells.
PMID- 9645450
TI - Primary manifestation of Hodgkin's disease in the central nervous system.
AB - A 62-year-old woman presented with loss of memory and a mild hemiparesis.
Neuroradiology demonstrated a left frontoparietal tumour. Biopsy specimens of
this lesion revealed intracerebral Hodgkin's lymphoma, a diagnosis supported by
immunohistochemical reactions of the tumour cells for the CD30 antigen.
Additional cell cycle studies revealed a high proliferative activity of the
tumour cells in association with absence of apoptosis. There was no evidence that
overexpression of bcl-2 or Epstein-Barr virus infection was involved in the
pathogenesis of this neoplasm. Lymphomas in the lung were detected 3 months
later. Following neurosurgical excision, radiotherapy, and chemotherapy, the
patient had no evidence of Hodgkin's disease after 13 months of follow-up.
PMID- 9645451
TI - Expression of Lewis antigens in papillary carcinoma of the thyroid gland.
PMID- 9645452
TI - Microsatellite instability is rare in the clinical course of myelodysplastic
syndrome studied with DNA from fresh and paraffin-embedded tissues.
AB - Microsatellite instability (MSI) has been reported to occur in various types of
malignant neoplasms. We performed a polymerase-chain-reaction-based assay for MSI
between the initial and the most recently available ("latest") samples from 23
patients with myelodysplastic syndrome (MDS). Of these patients, 15 were
informative at more than three microsatellite loci. Seven patients showed an
increase in leukemic cells while 8 patients did not during the interval between
the two analyses. Only 1 of the patients, who had refractory anemia with excess
blasts, which changed to acute myelogenous leukemia, showed microsatellite
alteration at the analysis times. Among all 23 patients, two alterations were
detected in the 42 informative paired samples that showed an increase in leukemic
cells (4.8%), while none was detected in the 59 paired samples without such an
increase. In total, therefore only two alterations were detected among 101
informative paired samples (2%). This indicates that MSI is rare in the clinical
course of MDS irrespective of disease status, and is consequently not a critical
genetic event for disease progression in most MDS patients.
PMID- 9645453
TI - Greater antitumor efficacy of paclitaxel administered before epirubicin in a
mouse mammary carcinoma.
AB - Combined treatment with paclitaxel and anthracyclines is increasingly being
tested in clinical practice. Epirubicin is in general administered before
paclitaxel. We have investigated, using a murine mammary adenocarcinoma, whether
the efficacy and toxicity of this combination is influenced by treatment
sequence, different time intervals and dose intensity. The tumor was transplanted
into the right hind foot of C3D2F1 female mice. Paclitaxel was administered i.p.
in doses ranging from 15 mg/kg to 75 mg/kg and epirubicin (i.p. or i.v.) in doses
from 9 mg/kg to 30 mg/kg. The hepatic and peritoneal toxicity observed with
epirubicin administration increased in combined treatments (stronger with i.p.
than i.v. epirubicin administrations) and was dose-dependent. When paclitaxel and
epirubicin were administered simultaneously or paclitaxel was given 24 h before
epirubicin, the same tumor growth delays were obtained in all groups. A smaller
effect was observed when paclitaxel was administered 24 h after epirubicin.
Increasing the epirubicin or paclitaxel dose led to higher tumor growth delays
but also an increased toxicity. In conclusion, in this experimental model, the
administration of 45 mg/kg paclitaxel before 15 mg/kg epirubicin was very
effective and the increased toxicity can be limited by introducing an interval of
24 h between drug administrations. These results should be considered when
designing clinical trials.
PMID- 9645454
TI - Expression of the active form of MMP-2 on the surface of leukemic cells accounts
for their in vitro invasion.
AB - The enhanced expression of matrix metalloproteinases (MMP), especially
gelatinases MMP-2 and MMP-9, has been associated with the invasive behavior of
tumor cells. Previously we reported that primary acute myelogenous leukemia
blasts and human leukemic cultured KG-1 cells but not HEL cells penetrate a
reconstituted basement membrane (Matrigel) in an invasion assay. In this study,
we investigated the role of MMP-2 and MMP-9 in in vitro invasion by leukemic
cells. We found that both recombinant human tissue inhibitor of metalloproteinase
2 (rhTIMP-2) and anti-MMP-2 antibody inhibit the invasiveness of KG-1 cells in
the Matrigel assay (by 76% and 51% respectively), while anti-MMP-9 antibody does
not, indicating that MMP-2 but not MMP-9 in involved in the invasive process. KG
1 cells were found to secrete constitutively the latent (but not the activated)
forms of both MMP-2 and MMP-9 and, after stimulation with the phorbol ester 12-O
tetradecanoylphorbol 13-acetate (TPA), higher levels of these pro-MMP. TPA
stimulation, however, did not increase the in vitro invasiveness of these cells.
Analysis by Western blot and flow cytometry revealed the presence of the
activated form of MMP-2 (64 kDa) on the surface of KG-1 cells and primary AML
blasts, as well as MT-MMP in the homogenates of these cells. This active form of
MMP-2 was not detected on the surface of HEL cells, which were non-invasive in
vitro, although these cells secreted pro-MMP-2. In conclusion, leukemic KG-1 and
primary acute myelogenous leukemia cells, which secrete pro-MMP-2 and pro-MMP-9,
were also shown to express the activated form of MMP-2 on their cell surface. We
suggest that this active form is essential to the in vitro invasion of leukemic
cells.
PMID- 9645455
TI - The expression of the mdm2 gene may be related to the aberration of the p53 gene
in human hepatocellular carcinoma.
AB - The relationship between mdm2 gene expression and p53 gene mutation in
hepatocellular carcinoma (HCC) and their correlation with the invasiveness of the
disease were investigated in this study. Either the expression level of the mdm2
gene or the mutation rate of the p53 gene was higher in HCC than in paratumor
liver tissues. Studies on the relationship between mdm2 and p53 revealed that
mdm2 gene expression in HCC without p53 mutation was higher than when there was
p53 mutation, while the p53 mutation rate in HCC with mdm2 overexpression was
significantly lower than in HCC without mdm2 overexpression. Among 23 HCC with
invasion, mdm2 gene overexpression was found in 6 patients while p53 mutation was
found in the other 11 patients, and only 1 patient was found to have both mdm2
overexpression and p53 mutation. These results indicated that either mdm2
overexpression or p53 mutation may be related to the invasiveness of HCC.
Considering that an autoregulatory feedback loop between the mdm2 and p53 genes
may exist, wild-type P53 can induce the expression of mdm2 via a p53-binding site
in the mdm2 gene, while MDM2 protein functions as a negative regulator of P53
protein. These results also suggest that mdm2 may be related to the high
invasiveness of HCC through inactivating the tumor-suppressor function of the p53
gene.
PMID- 9645456
TI - Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth
factor FGF3 in nude mice.
AB - Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of
human Kaposi's sarcoma (KS) tumor tissues examined, while almost no expression of
FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were
constructed by the overlap-extension method. The proteins translated from two
FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be
the initiation codon, were shown to have the same molecular mass. This result
suggests that translation of human FGF3, which is different from mouse FGF3,
begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3
cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously
into athymic nude mice. Nodular lesions developed at the injection sites in all
seven mice injected with the F3-1 cell clone, which showed high expression of
FGF3, and in two out of six mice injected with the F3-2 cell clone, which
expressed a low level of FGF3. Histopathological features of these tumors
contained fascicles of spindle-shaped cells surrounding irregular endothelial
lined vascular clefts, similar to those observed in human KS lesions.
Immunohistochemical staining for factor V111 antigen revealed reactivity in
multiple areas, especially in abundant vascular structures of the tumor sections
examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2,
and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our
results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some
similarities to human KS tumors. In conclusion, our results demonstrate the
potential tumorigenic and angiogenic role of human FGF3.
PMID- 9645457
TI - Continuous-infusion granisetron compared to ondansetron for the prevention of
nausea and vomiting after high-dose chemotherapy.
AB - PURPOSE: The serotonin receptor antagonists effectively prevent emesis with
little toxicity when employed with standard doses of emetogenic chemotherapy. The
optimal approach to the prevention of the emesis associated with the high doses
of chemotherapy used for autologous stem cell transplantation is not known. A
randomized controlled trial was designed to assess the relative efficacy and
toxicity of granisetron compared to ondansetron in the setting of autologous stem
cell transplantation. METHODS: A group of 48 patients with breast cancer were
randomized in a double-blind fashion to receive either (1) granisetron as a 0.5
mg i.v. bolus 30 min. before chemotherapy followed by a continuous infusion of
0.04 mg/h (1 mg/day) for 7 days or (2) ondansetron as an 8-mg i.v. bolus 30 min
before chemotherapy followed by a continuous infusion of 1 mg/h (24 mg/day) for 7
days. All patients also received 10 mg dexamethasone/day i.v. for 7 days.
Chemotherapy consisted of 1500 mg cyclophosphamide per m2/day, 125 mg thiotepa m(
2) day(-1), and 200 mg carboplatin per m2/day all as a continuous infusion for 4
consecutive days. The two study arms were then compared for the incidence and
severity of nausea, incidence of emesis, number of salvage anti-emetics required,
cost, and toxicity. RESULTS: A total of 46 patients were evaluable. The treatment
arms were well-balanced for known risk factors for chemotherapy-induced nausea
and vomiting. Compliance with self-reporting of nausea and vomiting was poor but
indicated no difference between the two treatment arms. The average number of
anti-emetics required was 15.8 in both treatment arms and the average time to the
first dose of a salvage anti-emetic was 2.8 days in the granisetron arm and 2.9
days in the ondansetron arm. The incidence of headache was 36 % in the
granisetron arm and 39 % in the ondansetron arm. None of these differences was
statistically significant. The use of granisetron resulted in a cost saving of
6.5 %. CONCLUSION: There was no significant difference between granisetron and
ondansetron in either efficacy or toxicity. At our institution, the use of
granisetron resulted in a moderate cost saving.
PMID- 9645458
TI - The operative management of a malignant proximal humerus tumor represented by
secondary Paget's osteosarcoma.
AB - PURPOSE: Malignant tumors at the proximal humerus are an operative challenge.
Radical removal is a principal of tumor surgery but as much functionality as
possible should be retained. These conditions often conflict so a compromise has
to be reached. This paper proposes a solution to this dilemma, introducing an
operative approach, with a new modular prosthesis, to a secondary Paget's
osteosarcoma in the proximal humerus. METHODS AND RESULTS: A recently developed
humerus modular prosthesis is described, which has been implanted into a patient
with Paget's osteosarcoma. In these, mostly elderly, patients, successful
operative therapy should combine radical removal with early mobilization. Paget's
osteosarcoma is a recognized complication of the disease, and its prognosis is
poor. In our patient, the implanted humerus prosthesis allowed a limb-saving
procedure to be combined with radical removal of the tumor and postoperative
early mobilization. A 3-month follow-up yielded good results with no recurrence
of the disease and the patient had satisfactory movement. She was able to resume
normal daily life shortly after the operation. CONCLUSION: Implantation of a
modular prosthesis of the humerus may allow radical removal of a malignant tumor
in that area while achieving early motion. In the literature, amputation is often
advocated, as radical treatment with chemotherapy is not a successful option in
this elderly patient group. We think the alternative use of a modular prosthesis
of the humerus is possible in selected cases. We have encountered no other case
in the literature where a limb-saving procedure attempts to preserve as much
functionality as possible in Paget's osteosarcoma.
PMID- 9645459
TI - Improved long-term survival for unresectable hepatocellular carcinoma (HCC) with
a combination of surgery and intrahepatic arterial infusion of 131I-anti-HCC mAb.
Phase I/II clinical trials.
AB - Resectional therapy has been accepted as the only curative therapy for
hepatocellular carcinoma (HCC). Unfortunately, it is estimated that only 10% of
HCC are resectable at the time of diagnosis. Cytoreduction and sequential
resection offer a new hope for patients with unresectable HCC. Radioimmunotherapy
(RIT) is an attractive approach for cytoreduction. We have previously shown that
intrahepatic arterial 131I-labelled anti-HCC monoclonal antibody (131I-Hepama-1
mAb) could be used safely in combination with hepatic artery ligation for
treatment of unresectable HCC, and encouraging results have been achieved. In
this paper, the long-term survival and the prognostic factors in HCC patients
treated with radioimmunotherapy will be analysed. Sixty-five patients with
surgically verified unresectable HCC were treated with hepatic artery ligation
plus hepatic artery cannulation and infusion from 1990 to 1992. Thirty-two
patients were enrolled in a phase I-II clinical trial with infusion of 131I
radiolabelled anti-HCC monoclonal antibody (Hepama-1 mAb) via the hepatic artery
(the RIT group). Another 33 patients formed the group treated with intrahepatic
arterial chemotherapy (the non-RIT group). T cell subsets were measured in 24
patients and human anti-(murine Ig) antibody (HAMA) were monitored in the RIT
group. The 5-year survival rate was significantly higher in the RIT group than in
the chemotherapy group, being 28.1% compared to 9.1% (P < 0.05); this was mainly
a result of better cytoreduction and a higher sequential resection rate (53.1%
compared to 9.1%). Significant prognostic factors in the RIT group included
tumour capsule status and the number of tumour nodules. HAMA incidence and CD4+ T
lymphocytes influenced short-term, but not long-term survival. It is suggested
that intrahepatic-arterial RIT, using 131I-Hepama-1 mAb, combined with hepatic
artery ligation might be an effective approach to improve long-term survival in
some patients with unresectable HCC, which may successfully be made resectable by
intra-arterial infusion of 131I-Hepama-1 mAb.
PMID- 9645460
TI - Methodological problems of grading tumour regression: responders compared to non
responders.
PMID- 9645461
TI - Gene therapy: application to disease. The Seventh International Symposium of the
Hiroshima Cancer Seminar, November 1997, Hiroshima, Japan.
PMID- 9645462
TI - Pharmacoeconomic evaluation of high-dose chemotherapy and peripheral blood stem
cell support in high-risk or poor-prognosis malignancies.
AB - Discussion of the total costs and cost-effectiveness ratios of patients receiving
high-dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) is
controversial. In Germany, no reliable data are available, whereas in other
countries this issue has been extensively studied. We performed a
pharmacoeconomic evaluation on all patients (n = 37) treated with HDC and PBSCS
at our institution between July 1994 and June 1997. Patients suffered from high
risk or poor-prognosis breast cancer (n = 24), Hodgkin's disease (n = 3), high
grade non-Hodgkin's lymphoma (n = 4), multiple myeloma (n = 2), small-cell
cervical cancer (n = 1), malignant hystiocytosis (n = 1) and testicular cancer (n
= 2). For pharmacoeconomic evaluation, the period from initiation of induction
chemotherapy (IC) until reconstitution after the last course of HDC and PBSCS was
considered. A total of 18 patients received IC/HDC/PBSCS for locally advanced or
systemic disease, and 19 patients received adjuvant or consolidation
IC/HDC/PBSCS. Treatment protocols were heterogeneous. Patients were treated with
two to five courses (median two) respectively of IC and sequential mono-HDC (n =
26), tandem-HDC (n = 10) or triple-HDC (n = 1). All patients received
granulocyte/macrophage-colony-stimulating factor (G-CSF) for stem cell
mobilisation and for amelioration of neutropenia after HDC. The relative costs
(based on supplier prices) for the total amount of drugs prescribed during the in
patient period was 29.8% for G-CSF, 35.8% for blood products 18.5% for
chemotherapy, 2.4% for antiemetics, 5.9% for antimicrobial drugs and 7.6% for
other drugs. Contrary to expectations, antimicrobial drugs had only a minor
pharmacoeconomic impact during IC/HDC/PBSCS in patients with high-risk or poor
prognosis malignancies, indicating that prolonged septic complications were
uncommon in our institution. We conclude that pharmacoeconomic evaluations in IC/
HDC/PBSCS might be integrated into the effort to ensure quality control and
monitoring.
PMID- 9645463
TI - Perpetually mobile footprints of ancient infections in human genome.
AB - Up to 1% of the human genome is represented by human endogenous retroviruses
(HERVs) and their fragments that are likely footprints of ancient primate germ
cell infections by retroviruses that occurred 10-60 million years ago. HERV
solitary long terminal repeats (LTRs) can be often met in close vicinity to
functional genes. The LTRs comprise a set of regulatory sequences like promoters,
enhancers, hormone responsive elements and polyadenylation signals that might
come out as new regulatory signals to resident genes and thus change their
regulation in evolution. Moreover, the LTRs have a potential for chromatin
remodeling that can also modulate gene expression. This review describes the
integration specificity and distribution of the HERVs and LTRs in the human
genome and discusses possible functional consequences of their integration in the
vicinity of genes.
PMID- 9645464
TI - A novel system of peptidergic regulation.
AB - Systematic analysis of structure and biological activity of peptide components of
tissue extracts and biological fluids allows us to formulate a novel concept of a
peptidergic regulatory system, complementary to the conventional regulatory
systems (i.e. nervous, endocrine and paracrine systems). According to that
concept, the proteolytic degradation of tissue proteins carried out by a specific
and regulated system of tissue-specific enzymes and protein substrates gives rise
to a large group of peptides, which we define as tissue-specific peptide pool. As
a result, functional proteins provide their proteolytically derived fragments for
maintaining tissue homeostasis.
PMID- 9645465
TI - Effects of the amyloid protein precursor of Alzheimer's disease and other ligands
of the LDL receptor-related protein on neurite outgrowth from sympathetic neurons
in culture.
AB - The amyloid protein precursor (APP) of Alzheimer's disease can stimulate neurite
outgrowth in vitro. The receptor responsible for this effect has not been
identified. Kunitz protease inhibitor (KPI)-containing forms of APP bind to the
low-density lipoprotein receptor-related protein (LRP). As LRP may regulate
neurite outgrowth, we examined whether the effects of APP are mediated by LRP.
Inhibitors of LRP decreased neurite outgrowth from chick sympathetic neurons.
Most LRP ligands (alpha2-macroglobulin, lactoferrin, and lipoprotein lipase)
stimulated outgrowth. However, in soluble form, the KPI-containing APP751 was a
weak inhibitor of outgrowth. In substrate-bound form, both APP751 and APP695
(which does not bind to LRP) stimulated outgrowth. Thus the effect of substrate
bound APP on neurite outgrowth is not mediated by LRP.
PMID- 9645466
TI - Quantitative analysis of a cysteine351glycine mutation in the G protein Gi1alpha:
effect on alpha2A-adrenoceptor-Gi1alpha fusion protein activation.
AB - Fusion proteins were constructed between the porcine alpha2A-adrenoceptor and
either wild-type (Cys351) or a pertussis toxin-resistant (Gly351) form of the G
protein Gi1alpha. Addition of adrenaline to membranes expressing the fusion
proteins resulted in concentration-dependent stimulation of their high affinity
GTPase activity. The alpha2A-adrenoceptor-wild type Gi1alpha fusion protein
produced substantially higher maximal stimulation of GTPase activity in response
to adrenaline than that containing Gly351 Gi1alpha. Treatment of the fusion
proteins as agonist-regulated enzymes allowed measurement of Vmax and turnover
number for adrenaline-stimulation of the GTPase activity of each fusion
construct. The turnover number of the alpha2A-adrenoceptor-Cys351 Gly Gi1alpha
fusion protein was only 44'S, of that for the alpha2A-adrenoceptor-wild type
Gi1alpha fusion protein. These data provide the first direct quantitative
evaluation of the effects of a mutation of a G protein on the capacity of an
agonist-occupied receptor to activate the mutant.
PMID- 9645467
TI - Staurosporine-sensitive protein phosphorylation is required for postreplication
DNA repair in human cells.
AB - DNA repair is an important factor of stability of pro- and eukaryotic genomes
which plays a central role in mutagenesis and carcinogenesis. Genetic control of
nucleotide excision repair (NER) in mammalian cells is well studied, but little
is known about molecular mechanisms of postreplication repair (PRR) which allows
bypass of base lesions in template strands after DNA replication. In
Saccharomyces cerevisiae PRR is controlled by the RAD61RAD18 pathway which
involves POL30 gene encoding proliferating cell nuclear antigen (PCNA), and in
human cells PCNA is known to be closely associated with the newly replicated
chromatin where PRR probably takes place. In UV-irradiated human cells distinct
PCNA foci may be detected in some cells which accumulate phosphorylated breast
cancer susceptibility protein BRCA1 and another protein BARD1. Human PCNA is also
known to be phosphorylated after UV-irradiation. In this study we found that the
known inhibitor of protein kinases staurosporine supresses PRR in NER-deficient
cells which is consistent with the view that BRCA1 and PCNA are required for PRR.
We also have shown that the distinct PCNA foci in UV-irradiated NER-deficient
cells are actually associated with the newly replicated chromatin. Since RAD18
protein is not essential for normal DNA replication and directly controls PRR in
yeast, we analysed whether this protein as well as its human homologs (HR18A and
HR18B) have common domains with BRCA1 and BARD1. It is found that HR18A has a
subregion of homology to BARD1 and HR18A-to BRCA1. Taken together the results
indicate that BRCA1 and BARD1 may be involved in PRR in human cells.
PMID- 9645468
TI - The murine gap junction gene connexin36 is highly expressed in mouse retina and
regulated during brain development.
AB - A new gap junction gene isolated from rat brain cDNA, mouse retina cDNA and mouse
genomic DNA is called connexin36, since it codes for a connexin protein of 321
amino acids corresponding to the theoretical molecular mass of 36045 kDa (rat)
and 36084 kDa (mouse). Only one amino acid residue differs between rat and mouse
connexin36. In the single murine connexin36 gene, an 1.14-kb intron interrupts
the coding region, similar as in the homologous skate connexin35 gene. Because of
this unique feature, mouse connexin36 differs from the other 13 murine connexin
genes and is suggested to form a new delta subclass of connexins. Connexin36 mRNA
(2.9 kb) is highly expressed in adult retina and less abundant in brain where it
gradually increased during fetal development until day 7 post partum, and
decreased thereafter.
PMID- 9645469
TI - Metabolism of 8-iso-prostaglandin F2alpha.
AB - Tritium labelled (x=1.1 MBq/17.7 microg/kg) and unlabelled 8-iso-PGF2alpha (43
microg/kg) were administered intravenously to female rabbits and frequent blood
and continuous urinary samples were collected up to 4 h. The total radioactivity
was lost rapidly from the circulation. About 80% of the total radioactivity was
found in urine within 4 h. The plasma half-life of 8-iso-PGF2alpha is found to be
1 min at the distribution phase. The terminal elimination phase half-life was
about 4 min. At 1.5 min after administration 64%, 19% and 13% of the plasma
radioactivity represented 8-iso-PGF2alpha, 15-keto-8-iso-PGF2alpha and beta
oxidised products, respectively. The values for 20-min plasma were 5%, 2%, and
88%. The radiochromatograms from 10 min-4 h urinary samples were dominated by
more polar beta-oxidised products. Alpha-Tetranor-15-keto-13,14-dihydro-8-iso
PGF2alpha was identified as a major urinary metabolite.Thus, 8-iso-PGF2alpha
metabolises in the rabbit mainly to several degraded polar metabolites through
dehydrogenation at C-15, reduction of delta13-double bond and beta-oxidation, and
excretes efficiently into the urine.
PMID- 9645470
TI - Residues unique to the pro-hormone convertase PC2 modulate its autoactivation,
binding to 7B2 and enzymatic activity.
AB - The prohormone convertase PC2 is one of the major subtilisin/kexin-like enzymes
responsible for the formation of small bioactive peptides in neural and endocrine
cells. This convertase is unique among the members of the subtilisin/kexin-like
mammalian serine proteinase family in that it undergoes zymogen processing of its
inactive precursor proPC2 late along the secretory pathway and requires the help
of a PC2-specific binding protein known as 7B2. We hypothesized that some of
these unique properties of PC2 are dictated by the presence of PC2-specific amino
acids, which in the six other known mammalian convertases are otherwise conserved
but distinct. Accordingly, six sites were identified within the catalytic segment
of PC2. Herein we report on the site-directed mutagenesis of Tyr194 and of the
oxyanion hole Asp309 and the consequences of such mutations on the cellular
expression and enzyme activity of PC2. The data show that the Y194D mutation
markedly increases the ex vivo ability of PC2 to process proopiomelanocortin
(POMC) into beta-endorphin in cells devoid of 7B2, e.g. BSC40 cells. In these
cells, expression of native PC2 does not result in the secretion of measurable in
vitro activity against a pentapeptide fluorogenic substrate. In contrast,
secreted Y194D-PC2 exhibited significant enzymatic activity, even in the absence
of 7B2. Based on co-immunoprecipitations and Western blots, binding assays
indicate that Tyr194 participates in the interaction of PC2 with 7B2, and that
the oxyanion hole Asp309 is critical for the binding of proPC2 with pro7B2.
PMID- 9645471
TI - Plasma membrane NADH-coenzyme Q0 reductase generates semiquinone radicals and
recycles vitamin E homologue in a superoxide-dependent reaction.
AB - We investigated the ability of plasma membrane CoQ reductase (PMQR) purified from
pig liver to reduce phenoxyl radicals of a vitamin E homologue, Trolox. We report
that NADH-driven one-electron reduction of CoQ0 catalyzed by PMQR produced CoQ0
semiquinone radical and CoQoH2. These in turn, recycle vitamin E homologue,
Trolox, via reducing its phenoxyl radical. A significant part of NADH/PMQR
catalyzed reduction of CoQ0 (and Trolox recycling) was superoxide-dependent.
Overall, our results demonstrate that PMQR in the model system used can act as an
antioxidant enzyme that recycles water-soluble homologues of coenzyme Q and
vitamin E.
PMID- 9645472
TI - Inhibition of ascorbate peroxidase under oxidative stress in tobacco having
bacterial catalase in chloroplasts.
AB - To analyze the potential of the active oxygen-scavenging system of chloroplasts,
we introduced Escherichia coli catalase into tobacco chloroplasts. Photosynthesis
of transgenic plants was tolerant to high irradiance under drought conditions,
while the wild plants suffered severe damage in photosynthesis under the same
conditions. Irrespective of responses to the stress, ascorbate peroxidase was
completely inactivated both in the transgenic and wild-type plants. These
findings are contrary to the established idea that the ascorbate peroxidase
mediated antioxidative system protects chloroplasts from oxidative stress.
PMID- 9645473
TI - The role of keratin filaments during nuclear envelope reassembly in Xenopus egg
extracts.
AB - We report here a new structure, named 'strings-of-pearls', which are seen to form
in Xenopus egg extracts after incubation, as 200 nm membrane vesicles attach to
10 nm filaments. These membrane vesicles fuse together along the filaments to
form annulate lamellae (AL) or attach to demembranated sperm chromatin to
initiate assembly of a nuclear envelope. Immunoassay with anti-keratin antibodies
AE3 showed that the filaments were mainly composed of a 56 kDa keratin-like
protein. Addition of AE3 to the extracts resulted in inhibition of AL formation
and defective assembly of NE. These results suggest a function of keratins in the
assembly of nuclear envelopes during Xenopus development.
PMID- 9645474
TI - Contribution of arginine-82 and arginine-86 to catalysis of RNases from Bacillus
intermedius (binase).
AB - To elucidate the functional role of Arg82 and Arg86 in the enzyme activity of
binase, the extracellular ribonuclease of Bacillus intermedius, we used site
directed mutagenesis. On cleavage of various substrates the catalytic activity of
binase mutant Arg86 Ala is 2.7 x 10(3) - 7.7 x 10(3) times less than that of the
native enzyme. The decrease in activity is determined preferentially by the
decrease in the molecular rate constant kcat with a relatively small change of
enzyme-substrate affinity, characterized by Km. This is the expected result if
Arg86 acts to lower the energy of a transition state of the reaction. The
replacement of Arg82 by Ala causes a 5-19-fold activity decrease, depending on
the substrate. We propose that this residue does not have a direct catalytic
function in the molecular mechanism of the binase action and that the activity
decrease of binase on the replacement of Arg82 by alanine is mediated by the
effect of Arg82 on the pK of catalytic residues.
PMID- 9645475
TI - A synthetic human Agouti-related protein-(83-132)-NH2 fragment is a potent
inhibitor of melanocortin receptor function.
AB - Chemical synthesis of Agouti proteins - Agouti and Agouti-related proteins - is
complicated by their large size and by multiple cysteine residues located in the
carboxyl terminal regions. Three human Agouti-related protein (AGRP) fragments,
two of which correspond to a proposed endoprotease cleavage site between amino
acids 82 and 83, were synthesized and tested for anti-melanotropic activity using
Xenopus laevis dermal melanophores. Amino-terminal fragments AGRP(25-51) and (54
82) were devoid of significant antagonist activity, whereas the amidated carboxyl
terminal AGRP fragment (83-132)-NH2 was potently active with an inhibitory
equilibrium dissociation constant (Ki) of 0.7 nM. The ability to synthesize
functionally active AGRP should help unravel its role in the central nervous
system and its unusual properties with respect to interaction with the
melanocortin family of G-protein coupled receptors.
PMID- 9645476
TI - Human natural resistance-associated macrophage protein is a new type of
microtubule-associated protein.
AB - Natural resistance-associated macrophage protein 1 (NRAMP1) is a putative
membrane protein that dominates natural resistance to infection. An NRAMP1
glutathione S-transferase fusion protein was used to test the ability of the
NRAMP1 NH2-terminal domain to bind to taxol-stabilized microtubules. Co
sedimentation analysis showed that the fusion protein binds to microtubules.
Although the NH2-terminal domain of the NRAMP1 molecule has structural homology
with the Pro-rich region of microtubule-associated protein 4 (MAP4), the presence
of the MAP4 microtubule-binding domain fragment had little effect on the binding
of the fusion protein to microtubules.
PMID- 9645477
TI - Efficient introduction of alkene functionality into proteins in vivo.
AB - The methionine analogue 2-amino-5-hexenoic acid (homoallylglycine, Hag) can be
utilized by Escherichia coli in the initiation and elongation steps of protein
biosynthesis. Use of an E. coli methionine auxotroph and Hag-supplemented medium
resulted in replacement of ca. 85% of the methionine residues in mouse
dihydrofolate reductase expressed under control of a bacteriophage T5 promoter. N
terminal sequencing indicated 92+/-5% occupancy of the initiator site by Hag. The
vinyl function of Hag remains intact in the purified protein and suggests new
chemistries for modification of natural and artificial proteins prepared in
bacterial hosts.
PMID- 9645478
TI - Mutational analysis of Caenorhabditis elegans CED-4.
AB - Much of our knowledge concerning the genetics that regulate cell death has come
from the studies of cell death during the development of the nematode
Caenorhabditis elegans. Of the 14 genes identified as components of nematode cell
death pathways, two genes, ced-3 and ced-4, are required to promote cell death
and a third, ced-9, blocks cell death. Recent studies show CED-4 to be an
activator of CED-3 and CED-9 to be an inhibitor of CED-4. Two published sequence
alignments suggest that CED-4 contains a death effector domain (DED), a protein
sequence motif present in other death signaling proteins like Fadd and Flice; one
study suggests a DED sequence similarity near the N-terminus while the other
found sequence similarity near the C-terminus of CED-4. Using mutational analysis
we have tested the functional significance of the conserved residues found within
the putative DEDs of CED-4. Mutations in two conserved residues within the
putative N-terminal DED of CED-4 affected its function, while mutations in the
conserved residues within the putative C-terminal DED had no effect on CED-4
function. Our results do not support the presence of a DED in the C-terminus of
CED-4 and suggest a potential role for the N-terminus in CED-4 function, possibly
as a DED or as a CARD (caspase recruitment domain). We also found that CED-9
associated with all the CED-4 mutants and inhibited the activity of all the
active-CED-4 mutants.
PMID- 9645479
TI - Constitutive and inducible type 1 ribosome-inactivating proteins (RIPs) in
elderberry (Sambucus nigra L.).
AB - Two novel highly basic type 1 (single chain) ribosome-inactivating proteins
(RIPs) with N-glycosidase activity have been found in elderberries (the fruits of
Sambucus nigra L.). Mass spectrometry of these RIPs, which we named nigritins f1
and f2, gave Mr values of 24095 and 23 565, respectively. Both proteins strongly
inhibited protein synthesis in rabbit reticulocyte lysates but were inactive
against plant ribosomes. Both nigritins have a similar topological activity on
pBlueScript SK+ DNA as that displayed by dianthin 30. Nigritin f1 is a
constitutive RIP since it is present in both green and mature intact elderberries
at nearly the same proportion with respect to total fruit protein. By contrast,
nigritin f2 is inducible and only appeared in mature intact elderberries.
Elderberries also contain two isoforms of a basic nigrin equivalent to the
recently found basic nigrin b in elder bark (De Benito et al., FEBS Letters 413
(1997) 85-91). Our results indicate that probably not all plant RIPs exert the
same biological function and that this may be determined by the physiological
state of the tissue.
PMID- 9645480
TI - N-copine: a novel two C2-domain-containing protein with neuronal activity
regulated expression.
AB - Neuronal activity is often associated with changes in gene expression. By a two
dimensional cDNA-display system, restriction landmark cDNA scanning, we
identified a novel gene whose expression in the hippocampus was up-regulated by
kainate stimulation. The mRNA expression was detected only in brain and up
regulated by the stimulation evoking CA3-CA1 long-term potentiation. The encoded
protein contains two copies of C2-domain, known as the Ca2+-binding domain of PKC
gamma, and shows 49% identity with human copine I. We designated this protein N
copine (neuronal-copine). N-copine may have a role in synaptic plasticity.
PMID- 9645481
TI - Identification of two forms of the gamma subunit of G protein, gamma10 and
gamma11, in bovine lung and their tissue distribution in the rat.
AB - Two forms of the gamma subunit of G protein were purified from bovine lung, and
were identified as gamma10 and gamma11 by analyses of partial amino acid
sequences and reactivity with specific antibodies. The N-terminal amino acid
residue of gamma11 was an unmodified Pro2, and the purified gamma11 was freed
from beta even under non-denaturing conditions. Western blots with specific
antibodies against gamma10 and gamma11 showed that both gamma subunits are
present in a variety of tissues in the rat, with a particular abundance of
gamma11 in the platelets.
PMID- 9645482
TI - Cationic uncouplers of oxidative phosphorylation are inducers of mitochondrial
permeability transition.
AB - To determine whether cationic uncouplers of oxidative phosphorylation induce
permeability transition in mitochondria, the effects of the divalent cationic
sulfhydryl cross-linker copper-o-phenanthroline (Cu(OP)2) and the cyanine dye tri
S-C4(5) on rat liver mitochondria were examined. Like Ca2+, they accelerated
mitochondrial respiration with succinate and induced mitochondrial swelling when
inorganic phosphate (Pi) was present in the incubation medium. The acceleration
of respiration and swelling were inhibited by the SH-reagent N-ethylmaleimide,
and by the specific permeability transition inhibitor cyclosporin A (CsA). In
addition, these cations, like Ca2+, induced release of ADP entrapped in the
mitochondrial matrix space, and the morphological change of mitochondria induced
by these cations was essentially the same as that induced by Ca2+. It is
concluded that the uncoupling actions of Cu(OP)2 and tri-S-C4(5) are due to
induction of permeability transition in the inner mitochondrial membrane.
PMID- 9645483
TI - Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA
bases by 5-aminolevulinic acid.
AB - 5-Aminolevulinic acid (ALA) is a heme precursor, pathological accumulation of
which is associated with liver cancer. We show that the reactive oxygen species
produced upon ALA metal-catalyzed oxidation promote the formation of several
radical-induced base degradation products in isolated DNA. The distribution of
modified bases is similar to that obtained upon gamma irradiation. This
observation strongly suggests the involvement of hydroxyl radicals in the ALA
mediated DNA damage. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and
5-hydroxy-2'-deoxycytidine in organ DNA of rats chronically treated with ALA were
observed. This is strongly suggestive of the implication of hydroxyl radicals in
the ALA-induced degradation of cellular DNA.
PMID- 9645484
TI - Vitamin C attenuates nitrate tolerance independently of its antioxidant effect.
AB - In LLC-PK1 kidney epithelial cells, a 5-h pretreatment with glyceryl trinitrate
(GTN) resulted in substantial desensitization of the intracellular cyclic GMP
response to a subsequent 10-min challenge with GTN (1 microM). GTN-tolerant cells
were fully sensitive to the spontaneous nitric oxide (NO) donor spermine NONOate,
which does not require enzymatic bioactivation. Cyclic GMP stimulation by GTN was
up to 3.1-fold higher when vitamin C (1-10 mM) was present during the
pretreatment period. In contrast, other oxygen radical scavengers such as tiron
or dimethylsulfoxide and the NO scavenger PTIO left tolerance induction
unaltered. Together, our results suggest that reactive oxygen species or NO do
not contribute to the development of nitrate tolerance. Tolerance reduction by
vitamin C may be due to a stabilizing effect on enzymes involved in the
bioconversion of GTN to NO.
PMID- 9645485
TI - Dipeptidyl peptidase IV (DP IV, CD26) is involved in regulation of DNA synthesis
in human keratinocytes.
AB - Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV
(DP IV, CD26), expressed on T, NK, and B cells in the human immune system, is
involved in the regulation of DNA synthesis and cytokine production. Here, we
clearly demonstrate that this enzyme is highly expressed also on human epidermal
foreskin and split-skin keratinocytes and that the specific DP IV inhibitors
Lys[Z(NO2)]-thiazolidide, Lys[Z(NO2)]-pyrrolidide inhibit the enzymatic activity
as well as the DNA synthesis of these cells. These data demonstrate that CD26
plays a role also in regulation of DNA synthesis of epidermal keratinocytes and
that the enzymatic activity is required for mediating these effects.
PMID- 9645486
TI - Cloning and expression of the gene for a vanadium-dependent bromoperoxidase from
a marine macro-alga, Corallina pilulifera.
AB - The cDNAs for a vanadium-dependent bromoperoxidase were cloned from a marine
macro-alga, Corallina pilulifera. The open reading frame of one clone (bpo1)
encoded a protein of 598 amino acids with a calculated molecular mass of 65312 Da
in good agreement with that of 64 kDa determined for the native enzyme. The
deduced amino acid sequence coincided well with partial sequences of peptide
fragments of the enzyme. From the same cDNA library we also isolated another cDNA
clone (bpo2) encoding a protein of 597 amino acids with an identity of about 90%
to BPO1, suggesting a genetic diversity of the bromoperoxidase gene of C.
pilulifera growing in a relatively narrow area. The carboxy-terminal 123 residues
of the enzyme (BPO1) showed an identity of 45% to that of the marine macro-alga
Ascophillum nodosum. The homology search of the sequences of bromoperoxidases
from C. pilulifera (this study) and A. nodostum, and chloroperoxidase from the
fungus Curvularia inaequalis indicated highly conserved sequences PxYxSGHA and
LxxxxAxxRxxxGxHxxxD. Furthermore, it was found that the histidine residue
directly bound to vanadium, other residues building up the metal center and
catalytic histidine residue forming the active site of the chloroperoxidase from
C. inaequalis are conserved in the primary structure of the bromoperoxidase from
C. pilulifera. The cloned hpol was introduced into Escherichia coli, and the
expressed PO1 was purified from the recombinant strain. The N-terminal amino acid
sequence of the purified BPO1 was identical to the deduced sequence from the cDNA
except the N-terminal methionine.
PMID- 9645487
TI - Two immunoglobulin-like domains of the Z-disc portion of titin interact in a
conformation-dependent way with telethonin.
AB - The giant muscle protein titin/connectin plays a crucial role in
myofibrillogenesis as a molecular ruler for sarcomeric protein sorting. We
describe here that the N-terminal titin immunoglobulin domains Z1 and Z2 interact
specifically with telethonin in yeast two-hybrid analysis and protein binding
assays. Immunofluorescence with antibodies against the N-terminal region of titin
and telethonin detects both proteins at the Z-disc of human myotubes. Longer
titin fragments, comprising a serine-proline-rich phosphorylation site and the
next domain, do not interact. The interaction of telethonin with titin is
therefore conformation-dependent, reflecting a possible phosphorylation
regulation during myofibrillogenesis.
PMID- 9645488
TI - Ganglioside GM2 is substrate for a sialidase in MDCK cells.
AB - GM1 ganglioside carrying a fluorescent fatty acid in substitution of the natural
one, has been administered to cultured Madin-Darby canine kidney (MDCK) cells for
different pulse times (0.5-24 h), and its metabolic fate was followed. The
fluorescent GM2, asialo-GM2, asialo-GM1 and ceramide were the only detectable
metabolites. The complete absence of fluorescent GM3 is consistent with the
presence in these cells of a sialidase working on GM1 and GM2 gangliosides. After
treatment of the cells with chloroquine the fluorescent GM1 remained essentially
undegraded, indicating a catabolic processing at lysosomal level.
PMID- 9645489
TI - A role of neutrophils in the down-regulation of IL-6 and CD14 following
hemorrhagic shock.
AB - Hemorrhagic shock (HS) followed by resuscitation has been shown to initiate a
series of events, including local cytokine production and PMN accumulation. To
determine whether PMN are involved in the regulation of IL-6 expression in the
liver or lungs, IL-6 mRNA levels were measured in rats made neutropenic by
vinblastine pretreatment prior to HS. IL-6 mRNA levels were determined at 4 or 24
h following resuscitation from shock. Vinblastine alone in normal rats or sham
treated rats had no effect at 4 or 24 h. Vinblastine pretreatment had no effect
on the HS-induced increase in IL-6 mRNA at 4 h but dramatically increased levels
in both liver and lung at 24 h. Peripheral PMN counts were reduced by 95% in all
vinblastine-treated animals. Similar changes seen in CD14 mRNA expression
indicate that these effects are not limited to IL-6. These data show that normal
PMN levels are not needed for induction of IL-6 and CD14 in HS, and suggest that
PMN accumulation down-regulates the expression of these genes.
PMID- 9645490
TI - Dithiocarbamates enhance tumor necrosis factor-alpha production by rabbit
alveolar macrophages, despite inhibition of NF-kappaB.
AB - The tissue-fixed macrophage (Mphi) plays a key role in coordinating the excessive
inflammatory response following shock or sepsis. Reactive oxygen intermediates
have been recently described as second messengers involved in signal transduction
in these cells, including the activation of the transcription factors NF-kappaB
and AP-1. The dithiocarbamates are potent antioxidants that inhibit NF-kappaB
activation. We postulated that dithiocarbamates would inhibit Mphi activation via
inhibition of NF-kappaB. Rabbit alveolar Mphi were obtained by bronchoalveolar
lavage and exposed to either pyrrolidine dithiocarbamate (PDTC) or diethyl
dithiocarbamate (DDTC) followed by stimulation with LPS (10 ng/mL). Supernatants
were analyzed for TNF and prostaglandin E2, (PGE2) and F2-isoprostane (ISP), a
marker of membrane lipid peroxidation, production at 18 h. PDTC and DDTC
significantly enhanced production of TNF while inhibiting PGE2 and ISP production
compared with LPS alone (p < .05). Northern blots revealed increased mRNA for TNF
after pretreatment with PDTC, compared with LPS alone. Western blots and
oligonucleotide gel shifts of nuclear proteins revealed inhibition of NF-kappaB
activation by both PDTC and DDTC. AP-1 activity was shifted to earlier time
points by PDTC pretreatment. These results demonstrate transcriptional and
functional enhancement of TNF production despite inhibition of NF-kappaB
activation. This may be due in part to a loss of autocrine feedback inhibition by
PGE2 and enhancement of AP-1 activity. On the basis of these results, we conclude
NF-kappaB may be necessary but, in contrast to prior analyzes, is not sufficient
for optimal response of the alveolar Mphi to endotoxin.
PMID- 9645491
TI - Effect of melatonin on activated macrophage TNF, IL-6, and reactive oxygen
intermediates.
AB - Melatonin has recently been investigated as a biological response modifier in
sepsis and hypovolemic shock. Although melatonin is reported to influence a
variety of inflammatory and immune responses, evidence supporting its effects on
important macrophage-derived mediators is incomplete. This study was designed to
determine whether melatonin alters the release TNF, IL-6, and reactive oxygen
intermediates by activated macrophages. TNF and IL-6 bioactivity in LPS
stimulated Wistar rat alveolar macrophage and RAW 264.7 cell culture supernatants
were unchanged by pretreatment with melatonin. Similarly, macrophage production
of reactive oxygen intermediates, including H2O2 and superoxide anion, were
unaffected by melatonin pretreatment. PMA-stimulated H2O2 production was
determined in rat alveolar macrophages and RAW 264.7 cells. Superoxide anion
generation was determined in the rat alveolar macrophage NR8383 cell line.
Melatonin, at concentrations ranging from 10(-7) to 10(-4) M, does not alter LPS
stimulated TNF and IL-6, or PMA-stimulated H2O2 and superoxide anion production
by the macrophage populations studied. These observations are in contrast to
previous reports. Further studies are necessary to determine whether melatonin
indirectly influences macrophage function by actions on nonmacrophage cell
populations.
PMID- 9645492
TI - Platelet-activating factor is a key mediator of pulmonary vasoconstriction and
bronchoconstriction after antigen challenge in the perfused sensitized rabbit
lung.
AB - Exposure of sensitized perfused rabbit lungs to human O-N type erythrocytes leads
to pulmonary vasoconstriction and bronchoconstriction. To investigate whether
platelet-activating factor (PAF) is a mediator of pulmonary vasoconstrictive and
bronchoconstrictive responses after antigen challenge, we administered antigenic
erythrocytes after the administration of PAF antagonist (.1 mg/kg; CV6209).
Pulmonary arterial and airway pressures significantly increased after antigen
challenge in the sensitized rabbit lungs, but not in the nonsensitized rabbit
lungs. CV6209 significantly inhibited these pulmonary vasoconstrictive and
bronchoconstrictive responses after antigen challenge. We concluded that PAF, at
least in part, plays an important role in pulmonary vasoconstriction and
bronchoconstriction after antigen challenge in rabbits.
PMID- 9645493
TI - Effect of NG-nitro-L-arginine methyl ester on testicular blood flow and serum
steroid hormones during sepsis.
AB - Production of nitric oxide (NO) via NO synthase (NOS) has been implicated in the
regulation of steroidogenesis in normal physiology and septic pathophysiology.
The hypothesis that blockade of NOS by NG-nitro-L-arginine methyl ester (L-NAME)
would affect testicular blood flow and circulating levels of steroid reproductive
hormones was tested. Male Sprague-Dawley rats (350-450 g) were randomized to
septic and nonseptic groups. Sepsis was induced with an intraperitoneal (i.p.)
injection of a cecal slurry (200 mg/kg in 5 mL 5% dextrose in water (D5W)) in
rats, while nonseptic rats received only sterile D5W. The rats (n = 6 per group)
were catheterized in the jugular vein, left ventricle (via right carotid artery),
and tail artery to determine blood flow and systemic hemodynamics and to collect
blood at 24 h after induction of sepsis/sham sepsis. After baseline (24 h post
cecal slurry challenge) measurement, L-NAME (.50 mg/ kg x min) was infused
through the jugular vein for 10 min, blood flow was determined using a
radioactive microsphere technique, and blood samples were collected. The serum
concentrations of corticosterone, progesterone, and testosterone were determined
using radioimmunoassay. Plasma concentrations of NO byproducts (NOx) were
determined using the Greiss reaction. After 24 h, heart rate, testicular blood
flow, and NOx levels were significantly increased, whereas the serum
concentration of testosterone was significantly decreased in the septic group as
compared with the nonseptic group. However, serum concentrations of progesterone
and corticosterone at 24 h after induction of sham-sepsis or sepsis were not
statistically different. Infusion of L-NAME significantly reduced the testicular
blood flow and serum NOx levels in septic rats as compared with their baseline
values. The administration of L-NAME significantly increased the concentration of
testosterone in nonseptic and septic rats as compared with their respective basal
values. However, testosterone levels in septic rats were still significantly
lower than in nonseptic rats. The results of this study indicate that the
synthesis of NO through NO synthase may play a role in the regulation of
testicular blood flow and the serum levels of testosterone, associated with
chronic peritoneal sepsis in the rat.
PMID- 9645494
TI - Paradoxical changes in organ blood flow after arginase infusion in the non
stressed rat.
AB - Arginine (ARG) is the precursor of nitric oxide (NO), a potent vasodilator.
Arginase (ASE) is released following hepatocellular damage, resulting in low
plasma ARG levels. The effect of ASE infusion on hemodynamics was studied. Rats
received a 20 min ASE or saline infusion, and systemic hemodynamics and organ
blood flow were studied, at 30 and 270 min, using radiolabeled microspheres.
Compared with control, ASE resulted (30 min) in 1) undetectable ARG levels; 2)
higher mean arterial pressure and total peripheral resistance (both p < .05); 3)
higher blood flow to the heart, kidneys, stomach, small intestine (all p < .05),
and spleen (p < .001); and 4) lower vascular resistance in the heart, kidneys,
stomach, and small intestine (all p < .05) and in the spleen (p < .005). At 270
min, ASE rats had similar organ blood flow and higher nitrate levels in urine and
plasma (both p < .05) compared with control. We conclude that ASE reduces ARG
levels with simultaneous increase in mean arterial pressure and total peripheral
resistance. Higher nitrate production, suggesting higher NO formation in the
presence of low ARG plasma levels, is paradoxical but could explain the higher
blood flow in some organs. The increased total peripheral resistance during
higher nitrate formation suggests regional differences in dependency of NO
production on plasma ARG levels.
PMID- 9645495
TI - Effect of liposome-encapsulated hemoglobin on the development of endotoxin
induced shock in the rat.
AB - Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying
resuscitation fluid. Because LEH is cleared from the circulation primarily by the
reticuloendothelial system, its effect on the development of sepsis remains a
major concern. Thus, the present study aimed to evaluate whether LEH modifies
consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at
10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05)
and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by
3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later.
In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a
higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin
induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor
necrosis factor-alpha response without modifying its peak levels. LEH (n = 20)
did not exacerbate the endotoxin-induced tachycardia, leukopenia, and
thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin
induced responses was dependent on the time interval between LEH and endotoxin
administration as well as the endotoxin dose. The clinical relevance of these
results should be further investigated.
PMID- 9645496
TI - Time-dependent cardiovascular and inflammatory changes in acute endotoxemia.
AB - The pathophysiology of experimental acute endotoxemia is a complex process
involving both cardiovascular dysfunction and an inflammatory response. We have
examined the correlation in hemodynamic changes and the pulmonary inflammatory
response after lipopolysaccharide (LPS) administration with respect to time.
Importantly, we have measured the lung and plasma levels of nitric oxide (NO)
over time, as well as rapid generation of lung superoxide after LPS
administration. In anesthetized rats given a bolus injection of LPS (10 mg/kg
intravenously, from Salmonella enteritidis), mean arterial blood pressure dropped
by 63-70% within 15 min, and cardiac output fell by 57-63% within 20 min compared
with saline controls. Mean arterial blood pressure recovered slightly but was
still 51, 30, and 25% less than that of saline controls 45, 105, and 165 min
after LPS administration, respectively. Cardiac output remained depressed
throughout the experimental period and was 35% lower than in saline controls 165
min after LPS treatment. There was a small increase in plasma nitrite/nitrate as
an index of plasma NO production after 45 min and a 10-fold increase 165 min
after LPS addition compared with controls, strongly suggesting that NO mediates
the hypotension that occurs 165 min after LPS administration. Lung NO production
increased twofold 105 min after LPS administration and remained higher than in
saline controls. Histological sections showed that there was fluid accumulation
and alveolar collapse in the lung 45 min after LPS, whereas after 165 min, there
was extensive tissue damage and increased leukocyte accumulation compared with
controls. These results suggest that there was no correlation between early (1 h)
tissue damage and NO production. We found an increase in lung superoxide
generation 15 min after injection of LPS that coincided with the alterations in
cardiovascular function. These results suggest that early lung tissue damage
and/or hemodynamic changes may be due to superoxide generation from the lung.
PMID- 9645497
TI - Trauma-hemorrhage activates signal transduction pathways in mouse splenic T
cells.
AB - Severe impairment in the functions of immune-competent cells has been observed
following trauma and hemorrhage. Inappropriate release of cytokines during trauma
and hemorrhagic shock disrupt T lymphocyte functions and enable cells to activate
genes whose products are detrimental for maintaining a much-needed humoral and
cell-mediated immunity. The intracellular events for gene activation are mediated
by cytoplasmic transcription factors present as nascent (signal transducer and
activator of transcription 1 (STAT 1)) or as a complex (nuclear factor kappaB (NF
kappaB)). Receptor-initiated phosphorylation activates these transcription
factors prior to their nuclear translocation and binding to cognate DNA
sequences. Because T cell functions are critical to efficient functioning of the
immune system, we investigated whether expression of transcription factors, STAT1
and NF-kappaB, is perturbed in splenic T cells following trauma and hemorrhage.
To study this, enriched T cells harvested from spleens (pooled from three or four
mice per group) of sham, trauma (consisting of midline laparotomy), sham+trauma,
hemorrhage (blood pressure maintained at approximately 30 mmHg for 90 min
followed by adequate fluid resuscitation), and trauma+hemorrhage groups at 16-18
h after surgical procedure were probed for signal expressions in the presence and
absence of interferon-gamma using electrophoretic mobility shift and Western
immunoblot assay procedures. Hemorrhage with or without trauma induced activation
of Janus kinase 1, STAT1, and NF-kappaB in T cells. Stimulation of T cells with
interferon-gamma led to activation of all these signals in all groups including
experimental controls. STAT1 activation was accompanied by Janus kinase 1
phosphorylation, whereas NF-kappaB activation was mediated by phosphorylation and
rapid degradation of IkappaBalpha. These studies demonstrate that hemorrhagic
shock, with or without laparotomy, is sufficient to induce activation of
transcription factors in splenic T cells. Thus, attempts to prevent the
activation of transcription factors following hemorrhage by pharmacologic means
might be helpful for maintaining cell-mediated immunity under these conditions.
PMID- 9645498
TI - Pulmonary hypertension and reduced cardiac output during inhibition of nitric
oxide synthesis in human septic shock.
AB - It has been suggested that inhibitors of nitric oxide synthesis are of value in
the treatment of hypotension during sepsis. In this pilot study, we examined the
effects of inhibition of nitric oxide synthesis by continuous infusion of
N(omega)-nitro-L-arginine methyl ester (L-NAME) at 1.5 mg/kg/h in a patient with
severe septic shock. L-NAME produced a rise in mean arterial blood pressure and
systemic vascular resistance; catecholamine infusion could be reduced. Parallel
to these findings, there was a 50% reduction in cardiac output and a 5-fold rise
in pulmonary vascular resistance, which resulted in severe pulmonary hypertension
after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following
the termination of L-NAME infusion, pulmonary artery pressure and blood pressure
returned to baseline values, although pulmonary and systemic vascular resistance
remained elevated for several hours. We conclude that nitric oxide appears to
play a role in the cardiovascular derangements during human sepsis. Inhibition of
nitric oxide synthesis with L-NAME can increase blood pressure and systemic
vascular resistance. However, reduced cardiac output and pulmonary hypertension
are possible side effects of continuous NO synthase inhibition. These side
effects necessitate careful monitoring and may hinder the clinical application of
NO synthase inhibitors.
PMID- 9645499
TI - Lipid metabolism: new approaches to old problems.
PMID- 9645500
TI - Defects of lipoprotein metabolism in familial combined hyperlipidaemia.
AB - Familial combined hyperlipidaemia is the most common inherited hyperlipidaemia
and is found in up to 10% of patients with premature myocardial infarction. The
genetic and metabolic bases of the disorder have not yet been defined. This
review discusses the important advances in the past year in our understanding of
the different metabolic pathways contributing to the pathogenesis of familial
combined hyperlipidaemia.
PMID- 9645501
TI - Heterogeneity of apolipoprotein B-100-containing lipoproteins: what we have
learnt from kinetic studies.
AB - Apolipoprotein B-100-containing lipoprotein assembly is dependent on the
successive addition of triglyceride by microsomal transfer protein. Assembly may
end at this point and the lipoprotein secreted or it may continue with the bulk
addition of triglyceride by an unknown transfer process. These steps are
independently regulated and result in the secretion of a spectrum of
apolipoprotein B-100-containing particles. The production of small, dense LDL is
determined by the type of VLDL secreted by the liver. Large, triglyceride-rich
VLDL1 results in the formation of small, dense LDL through triglyceride exchange
and subsequent hydrolysis. Small, dense LDL are cleared from plasma relatively
slowly and tend to accumulate in the circulation where they exert their
atherogenic effects.
PMID- 9645502
TI - Structure and function of the plasma phospholipid transfer protein.
AB - Recent cloning and sequencing of plasma phospholipid transfer protein
complementary DNA revealed that phospholipid transfer protein belongs to the
lipid transfer/lipopolysaccharide binding protein family that includes the
cholesteryl ester transfer protein, the bactericidal permeability increasing
protein and the lipopolysaccharide-binding protein. In addition to structural
similarities, members of the lipid transfer/lipopolysaccharide-binding protein
family might share some common functional properties, and recent studies
demonstrated that phospholipid transfer protein can act in several distinct
metabolic processes. In particular, the molecular transfer of phospholipids,
unesterified cholesterol, alpha-tocopherol and lipopolysaccharides by
phospholipid transfer protein suggests that it might be involved both in
lipoprotein metabolism and in antimicrobial defence, resulting in a growing
interest in this protein.
PMID- 9645503
TI - The role of hepatic lipase in lipoprotein metabolism and atherosclerosis.
AB - In addition to its traditional role in the hydrolysis of lipoprotein
triglycerides and phospholipids, recent studies have implicated hepatic lipase in
other aspects of cellular lipid and/or lipoprotein metabolism and
atherosclerosis. Hepatic lipase may serve as a ligand that mediates the
interaction of lipoproteins to cell surface receptors and/or proteoglycans as
well as modulating aortic lesion development in different animal models. Over the
past several years significant advances have been made in our understanding of
new, alternative mechanisms by which hepatic lipase may modulate lipoprotein
metabolism and the development of atherosclerosis in vivo.
PMID- 9645504
TI - The lipolysis stimulated receptor: a gene at last.
AB - The lipolysis stimulated receptor is a lipoprotein receptor that was initially
described in 1992. In the presence of free fatty acids, the lipolysis stimulated
receptor recognizes either apolipoprotein B or apolipoprotein E, and as a
consequence, leads to the internalization and degradation of the lipoprotein
particles. Its affinity is highest for those lipoproteins most susceptible to
lipolysis, triglyceride-rich lipoproteins. Since the initial biochemical
identification and description of the lipolysis stimulated receptor, several
reports have been published by our group that provide circumstantial evidence for
its role in vivo for the clearance of triglyceride-rich lipid particles. In this
review, we bring the readers up-to-date on the evidence for the role of the
lipolysis stimulated receptor in lipoprotein metabolism, as well as the recent
developments in its molecular characterization.
PMID- 9645505
TI - New insights into bile acid transport.
AB - The enterohepatic circulation of bile acids is maintained by a series of membrane
transport proteins. Recent studies of the cloned sodium bile acid cotransporters
have provided new insights into their tissue expression, regulation, and their
relationship to cholesterol homeostasis and human diseases such as primary bile
acid malabsorption.
PMID- 9645506
TI - Role of muscle in triglyceride metabolism.
AB - It has long been recognized that skeletal muscle can contain modest stores of
triglyceride and that this depot of fuel can make a major contribution to energy
production during exercise. More recently, an adverse effect of muscle
triglyceride has begun to be defined within the context of insulin resistance.
Animal and clinical investigations have revealed a significant relation between
increased muscle triglyceride and insulin resistance, at least among mostly
sedentary individuals. These observations have stimulated the development, or at
least the refinement, of new methodologies to assess this aspect of 'regional'
fat deposition. In parallel, there has also been important new work designed to
enable better understanding of the factors that regulate muscle triglyceride and
to determine whether fatty acids taken up by skeletal muscle are oxidized or
stored, and how these pathways might be either altered by the presence of insulin
resistance or, in turn, contribute to the pathogenesis of insulin resistance.
PMID- 9645507
TI - Cholesterol, endothelial function and cardiovascular disease.
AB - Hypercholesterolaemia is associated with endothelial dysfunction and increased
risk of atheromatous disease. Although endothelial dysfunction has been
demonstrated early in the course of the disease process, it remains difficult to
establish a causal relationship. Despite this, endothelial function has been used
as a surrogate marker in small trials to identify and assess the effectiveness of
therapeutic interventions to reduce cardiovascular mortality, before large scale
clinical trials are undertaken. Recently, arterial stiffness has emerged as an
independent risk factor for cardiovascular disease and may provide a link between
hypercholesterolaemia, endothelial dysfunction, hypertension and stroke.
PMID- 9645508
TI - Lipid metabolism.
PMID- 9645509
TI - Nutrition and therapeutics.
PMID- 9645510
TI - Genetics and molecular biology.
PMID- 9645511
TI - Lipid metabolism.
PMID- 9645512
TI - Hyperlipidemia and cardiovascular disease.
PMID- 9645513
TI - Atherosclerosis: cell biology and lipoproteins.
PMID- 9645514
TI - Therapy and clinical trials.
PMID- 9645515
TI - Unicompartmental knee arthroplasty in middle-aged patients: a 2- to 6-year follow
up evaluation.
AB - Twenty-eight unicompartmental knee arthroplasties performed as an alternative to
high tibial osteotomy or tricompartmental knee arthroplasty in patients under 60
years of age were reviewed after 2 to 6 years of follow-up. The patient's age at
the time of operation averaged 52 years. Using the Knee Society Score, 90% were
rated good or excellent results in terms of function and pain relief. The average
flexion angle obtained was 124 degrees, and the average postoperative alignment
was 4 degrees of anatomic valgus for varus deformities and 8 degrees for valgus
deformities. The average activity level according to the Tegner and Lysholm score
slightly improved (preoperative, 2.3; follow-up, 2.7 points). Of the 28 knees, 9
(32%) presented radiolucent lines about the tibial component and two had
incomplete radiolucent lines at the bone-cement interface on the femoral side.
There was no correlation between activity level and tibial radiolucent lines. Two
revisions were performed because of loosening of the femoral component at the
prosthesis-cement interface. One was converted to another unicompartmental
arthroplasty and the other to a tricompartmental arthroplasty. One tibial
component exhibited an asymptomatic slowly progressive radiolucency.
Unicompartmental knee arthroplasty in middle-aged patients yields 2- to 6-year
results competitive with osteotomy but inferior to tricompartmental arthroplasty
in terms of revision. The specific prosthetic design used in this series appeared
to be vulnerable to femoral component loosening possibly because of constrained
tibial topography and smooth tapered femoral fixation lugs.
PMID- 9645516
TI - Unicompartmental arthroplasty: a long-term follow-up study.
AB - Seventy-three consecutive unicompartmental knee arthroplasties (UKAs) using a
Marmor-style non-metal-backed cemented tibial component were performed from 1975
to 1990. Sixty-seven knees (58 patients) were evaluated with minimum 5-year
follow-up (mean, 9.7 years; range, 5-20 years). Knee rating and patient function
were assessed using the updated Knee Society scoring system. Survivorship was 91%
at 5 years, 84% at 10 years, and 79% at 15 years. The mean knee rating for
surviving implants was 91 (range, 48-100), and mean functional score was 77
(range, 5-100). Survivorship and functional outcome were not affected by body
habitus, age, gender, or tibial component thickness. UKA offers long-term relief
of symptoms and excellent knee function in a high percentage of carefully
selected patients with single compartment gonarthrosis.
PMID- 9645517
TI - Complex primary and revision total knee arthroplasty using the condylar
constrained prosthesis: an average 5-year follow-up.
AB - The condylar constrained total knee arthroplasty was performed on 29 patients
undergoing 33 procedures and were reviewed clinically and radiographically at an
average follow-up of 5 years (range, 2-10 years). There were 21 women and 8 men.
The average age at the time of surgery was 70 years (range, 32-84). Of the 16
knees that were revision total knee arthroplasties, 8 had a previous infected
total knee arthroplasty, and 17 knees had severe deformities requiring the use of
the condylar constrained prosthesis. The patients were rated according to the
Knee Society clinical and radiological evaluation protocol. Measurements of
femoral and tibial component position were obtained as well as femoral tibial
angle, patella position, and cement bone radiolucencies. All clinical
measurements were made by an independent physical therapist. Clinical results
revealed an improvement from an average preoperative knee score of 38 points to
an average postoperative score of 86 points. The clinical results for 19 (58%)
knees were excellent, 8 (24%) had a good result, 1 (3%) was fair, 2 (6%) were
poor, and 3 (9%) were failures. The patients' average functional levels increased
from 24 to 58. The final average flexion was 96 degrees. Three knees have been
revised (9%). One was revised for recurrent infection, one for periprosthetic
fracture, and one for mechanical loosening of the tibial component. There were no
other knees with evidence of radiologic loosening. We conclude that the condylar
constrained total knee prosthesis provides an acceptable solution for revision
and complex primary total knee replacements at an intermediate follow-up term of
5 years.
PMID- 9645518
TI - Can a total knee replacement prosthesis be made entirely of polymers?
AB - We have prospectively studied 63 total knee replacements (TKR) in which the
femoral component was polyacetal, and 138 TKRs in which the femoral component was
conventional cobalt chrome. The tibial and patellar components were of ultrahigh
molecular weight polyethylene (UHMWPE). Patients were followed-up for at least 10
years. In the polyacetal group, a number of patients have died or have been
revised, for reasons unrelated to the presence of polyacetal. There were no
instances of femoral component fracture, nor failure by wear. One postmortem
specimen, retrieved at 9 years after surgery, showed no measurable polyacetal
wear and negligible HDP wear. The histology of tissue in contact with polyacetal
was indistinguishable from that adjacent to polymethyl methacrylate and UHMWPE in
the same knee. We believe that polyacetal could be used for the femoral component
of a TKR and that a further trial should be undertaken.
PMID- 9645519
TI - Femoral cement grading in total hip arthroplasty.
AB - The current gold standard for primary total hip arthroplasty is a cemented
femoral component combined with a porous-coated acetabular component. Barrack and
colleagues described a femoral cement mantle grading system which is increasingly
being used to evaluate surgical technique and to compare arthroplasty results.
The immediate postoperative radiographs of 100 primary total hip arthroplasty
cases from five community surgeons were assessed by three observers to evaluate
the overall quality of cement technique, the interobserver variability in cement
mantle grading, and specific characteristics of the grading system. All three
observers agreed on the grading in only 73% of the x-rays (anteroposterior view,
69%; lateral view, 77%). Compared with reports in the literature from specialized
hip arthroplasty centers, a very high proportion of the cases had grade C
mantles. To gain a balanced perspective of the global effectiveness and longevity
of cemented total hip arthroplasty it is important that follow-up studies be
reported upon from representative cross sections of the orthopaedic community.
PMID- 9645520
TI - Problems with the Rotaflex: a 10 year review of a rotating hinge prosthesis.
AB - The results of the first 10-year review of the Rotaflex total knee prosthesis are
presented. Loosening, fracture, implant failure, and damage to the extensor
mechanism have been frequent findings. Of 25 implants reviewed, an arthrodesis
has been performed in 4 patients and an amputation in 2. Surgery has been
declined in a further 4 patients. A brace is required by 7 of 19 patients in whom
the prosthesis has not been removed, and the results of surgery are considered
poor in 13 of these 19 patients. With an overall complication rate of almost 80%,
there would appear to be no place for this prosthesis despite its continued
availability.
PMID- 9645521
TI - Results of 1,000 Performance knees: cementless versus cemented fixation.
AB - A total of 893 patients with 1,000 Performance total knee prostheses were
retrospectively studied. The mean follow-up was 5.2 years. In 584 cases, the
femoral and tibial components were implanted using cementless techniques, and in
416 knees the femoral and tibial components were cemented. All patients received
a cemented all polyethylene patellar replacement. Tibial bone density determined
fixation type. The average age of patients with cementless fixation was 64.3
years versus 76.2 years for patients with cemented implants. The average
subjective and functional Knee Society scores were 91.2 and 90.1 for patients
with cementless knees and 89.6 and 83.5 for those with cemented replacements. A
surprising absence of osteolysis around screw fixation was noted, and at 5 years,
there was 99% implant survival.
PMID- 9645522
TI - Preoperative physical therapy in primary total knee arthroplasty.
AB - In order to evaluate the efficacy of preoperative physical therapy for patients
undergoing elective primary total knee arthroplasty, 10 patients completed 6
weeks of physical therapy before surgery (PT group). Ten patients served as
controls (C group). Subjects were tested at baseline (PT only), before surgery, 6
weeks after surgery, and 3 months after surgery using the Hospital for Special
Surgery knee rating scale, range of motion, thigh circumference, walking speed,
Cybex II isokinetic knee flexion, and extension testing, and computed tomography
scanning for cross-sectional muscle area. Hospital stay and need for physical
therapy after inpatient rehabilitation were also compared. Physical therapy
produced modest gains in isokinetic flexion strength in these severely arthritic
knees but no difference in extension strength. The decrease in isokinetic
strength after surgery was not affected by preoperative physical therapy. Muscle
area did not decrease significantly for the PT group, but it did decrease for the
C group after surgery. While postoperative strength differences could not be
demonstrated, preoperative physical therapy preserved thigh muscle area after
surgery. The clinical significance of this finding is uncertain. Consequently,
this study failed to support the routine use of preoperative physical therapy in
knee replacement surgery.
PMID- 9645523
TI - Bone loss around 2 different types of hip prostheses.
AB - Dual energy x-ray absorptiometry (DXA) allows the measurement of bone mineral
density (BMD) around an uncemented hip prosthesis. The aims of this study were:
1) to determine the reproducibility of periprosthetic BMD measurements; 2) to
delineate the time course of bone loss that occurs after insertion of a hip
prosthesis; and 3) to compare the bone loss around two different types of hip
prosthesis. We studied 20 patients: 11 had Bateman and 9 had porous-coated
anatomic prostheses inserted. The mean bone loss in 20 patients between 6 and 52
weeks after surgery was 6%. The greatest loss during this period was 18% and
occurred from the proximal medial cortex. We conclude that measurement of
periprosthetic bone mass by DXA is a precise technique. Bone loss was rapid in
the first 6 months following total hip replacement. There was no difference in
the bone loss occurring around the two prostheses studied.
PMID- 9645524
TI - The forces in the distal femur and the knee during walking and other activities
measured by telemetry.
AB - The forces and moments in the shaft of a distal femoral replacement were measured
by telemetry for a subject during different activities, and calculations were
then made of the forces at the knee. The axial force showed a small peak at heel
strike followed by two main peaks during stance. In level walking, the peak axial
force was between 1,487 and 1,718 N (2.2-2.5 BW), the peak shear force was 269
368 N (0.4-0.54 BW) directed anteriorly on the tibia, the peak axial torque was 7
Nm internal, while the patellofemoral force was 466-571 N. The highest axial
force was recorded for descending stairs (2.8 BW). Standing on one leg produced
2.4 BW, while lying supine and raising the leg produced 1.7 BW. The data produced
may resemble that of a normal subject, and has application to basic joint
mechanics, to joint reconstruction, and to total knee replacement design and
evaluation.
PMID- 9645525
TI - Acetabular reconstruction with impacted morselized cancellous allografts in
cemented hip arthroplasty: a histological and biomechanical study on the goat.
AB - Bone defects in total hip arthroplasty revision surgery can be restored with
different types of bone graft. The use of impacted morselized allograft chips in
combination with cement is the treatment of our choice. To establish the
incorporation capacity of the grafts and mechanical stability of the implant, an
animal model in the goat was developed. An acetabular defect was created and
restored with morselized grafts and a cemented cup. Postoperative performance of
the reconstruction was followed both histologically and biomechanically.
Histology showed that consolidation of the graft with the host bone bed had
occurred within 3 weeks. In the following period a front of vascular sprouts
infiltrated the graft. Graft resorption, woven bone deposition, and subsequent
remodeling resulted in a new trabecular structure. This structure contained only
scarce remnants of the original dead graft material. At the graft-cement
interface, graft resorption and new bone formation had resulted in areas of
direct vital bone-cement contact. Locally, a soft tissue interface was present.
After longer follow-up periods, progressive interface formation and loosening of
the cups were found in most animals. Mechanical testing showed that the stability
of the reconstruction increased during the first 12 postoperative weeks.
Thereafter, the stability decreased, probably by soft-tissue interface formation
at the graft cement interface. We conclude that cemented morselized allografts
have a high capacity to incorporate. Initial cup stability is adequate to provoke
graft incorporation with decreasing stability after the incorporation process has
been completed.
PMID- 9645526
TI - Porous-coated versus grit-blasted surface texture of hydroxyapatite-coated
implants during controlled micromotion: mechanical and histomorphometric results.
AB - Hydroxyapatite (HA)-coated implants with porous-coated and grit-blasted surface
textures were inserted bilaterally in a paired design into the medial femoral
condyles of eight dogs for 16 weeks. The implants were weight-loaded and
initially subjected to controlled micromotion of 500 microm during each gait
cycle. Histology revealed that five implants in each group had bony anchorage,
and the remaining implants were surrounded by fibrous tissue. Push-out testing
showed no difference in shear stiffness and strength, while energy absorption for
porous-coated implants was increased significantly by threefold. The HA coating
delaminated on grit-blasted implants during push-out testing, whereas porous
coated implants predominantly failed at the HA-tissue interface. Coverage,
surface area, volume, and thickness of the HA coating were significantly reduced
in vivo for porous-coated and grit-blasted implants. In conclusion, a plasma
sprayed porous-coated implant surface seems to give better fixation not only of
the HA-coating to the implant surface but also of the implant to the surrounding
tissues in comparison to a grit-blasted implant surface. The HA coating was
reduced more on fibrous-anchored than on bony-anchored implants, suggesting that
micromotion accelerates resorption of HA. Resorbed HA coating was replaced by
more bone on porous-coated implants than on grit-blasted implants, which suggests
that fixation of porous-coated implants will be durable.
PMID- 9645527
TI - Patellofemoral resurfacing. The value of instrumentation and design.
PMID- 9645528
TI - Misconceptions about patellofemoral resurfacing in total knee replacement.
PMID- 9645529
TI - Early osteolysis with Hylamer acetabular liners.
AB - We reviewed 78 patients with Hylamer acetabular liners (DePuy-Dupont Orthopedics,
Warsaw, IN), with a mean follow-up of 3.8 years (range, 2-6 years), for signs of
osteolysis secondary to polyethylene wear. Nine patients (11.5%) showed
osteolysis greater than 1 cm2. One patient had a greater trochanter fracture
through a lytic area, one patient required a revision at 4 years for severe
acetabular and femoral lysis with lesser trochanter fracture, and a second
patient is awaiting revision.
PMID- 9645530
TI - The use of femoral intramedullary nailing as an interim or salvage technique
during complicated total hip replacement.
AB - When performing a revision total hip replacement complicated by infection, severe
osteolysis, comminuted periprosthetic fracture, and/or extensive bone loss, a
single-stage procedure may not be feasible. This study reports four cases of
femoral intramedullary nailing as an interim or salvage technique during
complicated total hip replacement. This reconstruction provides axial and
rotational stability of the femur while maintaining femoral alignment.
Furthermore, this reconstruction facilitates early mobilization and
rehabilitation of the patient. This interim reconstruction can be converted to a
revision total hip replacement at a later time. Alternatively, the stabilized
resection arthroplasty may serve as a salvage technique if further reconstruction
is not indicated.
PMID- 9645531
TI - Supracondylar femur fractures above an Insall-Burstein CCK total knee: a new
method of intramedullary stem fixation.
AB - Supracondylar femur fracture above a well-fixed posterior cruciate substituting
prosthesis may not allow the use of standard fixation methods because of the
closed nature of the femoral box. The Insall-Burstein Constrained Condylar Knee
femoral prosthesis (Zimmer, Warsaw, IN) possesses a closed box and the capability
of modular femoral stems. A retrieval device aids the utilization of the modular
ability of the femoral prosthesis to gain intramedullary fixation of
supracondylar femur fractures above a well-fixed femoral component allowing
restoration of alignment, length, preinjury range of motion, and function.
PMID- 9645532
TI - Prosthetic knee Candida parapsilosis infection.
AB - We report a 77-year-old man who developed Candida parapsilosis infection
following total knee arthroplasty. Knee joint effusion was noted 2 weeks after
surgery, and repeated cultures of aspirated fluid established the diagnosis of
Candida parapsilosis infection 4 weeks after surgery. Treatment consisted of
debridement and lavage of the involved joint together with continuous irrigation
with fluconazole for 4 weeks, followed by oral fluconazole for another 6 months.
At 3 years follow-up, the patient was doing well and radiological examination of
the affected knee showed a firm attachment of the prosthesis. We suggest that
early identification of the causative organism followed by continuous irrigation
and use of appropriate antifungal medication may prevent joint instability and
spares the removal of the prosthesis.
PMID- 9645533
TI - More recent advances in cementing technique...cement centrifugation and vacuum
mixing have significantly improved the results of cement femoral implants.
PMID- 9645534
TI - Analysis of inter-fragmentary movement as a function of musculoskeletal loading
conditions in sheep.
AB - It is well accepted that inter-fragmentary movement influences the fracture
healing process. Small axial movement can stimulate callus formation whereas
larger shear movement delays the healing process. It is, therefore, essential for
optimal fracture healing to minimize shear and to control axial movement.
Unfortunately, the complex gap movements are mostly unknown under the large
variety of clinical as well as experimental conditions of fracture fixation. To
further understand the complex interactions of musculoskeletal loading and inter
fragmentary movements in bones and to reduce the need for animal experiments, a
three-dimensional (3D) musculoskeletal model of the left hind limb of a sheep was
developed. From 3D ground reaction forces and inverse dynamics, resultant joint
loading was determined over a gait cycle. Muscle and joint contact forces were
derived from an optimization routine and internal loads in the tibia and
metatarsus from beam theory. Finally, inter-fragmentary movements were calculated
from the bony loading condition and experimentally determined stiffness matrices
of monolateral AISF external fixator constructs. Both the joint contact forces at
the hip and gap movement of a mid-shaft tibial fracture agree with in vivo data
reported in the literature. The bones proved to be mainly axially loaded with
slightly increasing shear forces toward their ends. The results suggest that
inter-fragmentary movement of metatarsal fractures is fairly independent of the
fracture location whereas the movement increases in proximal tibial fractures
compared to those in the distal and diaphyseal tibia. Considerable shear movement
was found for all locations and external fixator mountings. However, shear
movement could be minimized with a cranio-lateral rather than a cranio-medial
shift from the cranial fixator plane.
PMID- 9645535
TI - Heat-induced changes in the mechanics of a collagenous tissue: pseudoelastic
behavior at 37 degrees C.
AB - The outcome of many clinical heat therapies depends on the post-treatment
structural integrity of the tissue. Unfortunately, there are few data on heat
induced changes in the mechanical properties of tissues due to temperature levels
commonly achieved in laser, microwave, and radio-frequency-based modalities.
Without such information, one cannot design optimal clinical protocols. Hence, we
present new findings on the uniaxial stress strain behavior at 37 degrees C of a
model collagenous tissue (chordae tendineae) both before and after thermal
damage. This damage was induced via a variety of different thermo-mechanical
loads: isothermal heatings at temperatures from 65 degrees C to 90 degrees C,
durations of heating from 120 to 3600 s, and isotonic loads during heating from 0
to 0.65 MPa. Our data reveal that chordae exhibit pseudoelastic responses both
before and after heating, but the extensibility, hysteresis, and compliance all
increase with increased thermal damage. Fortunately, these complex heat-induced
changes in behavior can be parameterized using a single measure of the prior
thermal damage. This will clearly simplify the requisite constitutive
formulations.
PMID- 9645536
TI - Validated computation of physiologic flow in a realistic coronary artery branch.
AB - The pulsatile flow field in an anatomically realistic model of the bifurcation of
the left anterior descending coronary artery (LAD) and its first diagonal branch
(D1) was simulated numerically and measured by laser Doppler anemometry. The
inlet velocity profiles used in the computer simulation and in the physical
experiments were physiologically realistic. The computational geometric model was
developed on the basis of a digitized arterial cast. The curvature of the LAD
over the cardiac surface leads to axial velocity profiles which are slightly
skewed towards the epicardial wall. Downstream of the bifurcation, a strong
skewing occurs towards the flow divider walls as a result of branching. Locally,
the wall shear stress component caused by the complex secondary velocity can be
as high as the axial component. The wall shear stress representation from a cell
based perspective exhibits low shear stress and large deviation from the time
averaged shear stress direction during systole. In diastole, the instantaneous
wall shear stress direction nearly corresponds to the mean direction. The
comparison of computed and measured axial velocity results shows generally good
agreement. In contrast to computed flow patterns in simpler geometries
constructed from cylindrical tubes, the flow field is found to be smoother,
presumably reflecting the adaptation of the vascular contour to the contained
flow.
PMID- 9645537
TI - Compliance mismatch may promote graft-artery intimal hyperplasia by altering
suture-line stresses.
AB - The role of graft-artery compliance mismatch in the development of distal
anastomotic intimal hyperplasia (DAIH) is not yet resolved. Although DAIH
develops at all surgically created anastomoses, increased compliance mismatch
does not lead to greater hyperplasia formation in end-to-end anastomoses, but in
end-to-side anastomoses, it leads to a profound increase in hyperplasia. The
current study was undertaken to determine whether suture-induced anastomotic
stresses could explain these findings. A large strain finite element analysis of
vascular wall mechanics was performed to compare the influence of compliance
mismatch on intramural stresses in end-to-end versus end-to-side anastomoses. A
novel modelling approach was implemented which includes suture-induced stress
concentrations. End-to-end and end-to-side graft-artery simulations were executed
using (1) artery (compliance = C = 0.44% kPa(-1)), (2) vein (C = 0.33% kPa(-1)),
and (3) Dacron (C = 0.14% kPa(-1)) grafts. Residual stresses due to axial tension
were included and the anastomoses were statically inflated to 13.3 kPa (100
mmHg). Elevated intramural stresses were found to exist at both the end-to-end
and end-to-side graft-artery junctions; however, in the end-to-end anastomosis,
the maximum anastomotic stress was not a function of the graft compliance,
whereas in the end-to-side anastomosis, the maximum stress was a strong function
of graft compliance. For the 45 degree end-to-side geometry considered in this
study, the maximum anastomotic stress concentration obtained using a stiff Dacron
graft was more than 40% greater than that obtained using a compliant artery
graft. In the end-to-end anastomosis, the Dacron graft led to a less than 5%
increase in maximum stress over the artery graft. Therefore, increased compliance
mismatch increases stresses and promotes DAIH in end-to-side junctions, but, it
has little influence on either stresses or DAIH in end-to-end junctions. Thus,
the proliferative influence of increased compliance mismatch on suture-line
hyperplasia in end-to-side anastomoses can be explained by the resulting increase
in intramural stresses. In addition, since high stresses were found in both
geometries, elevated suture-line intramural stresses may be an important
proliferative stimulus for intimal hyperplasia formation in all vascular
reconstructions.
PMID- 9645538
TI - Standard mechanical energy analyses do not correlate with muscle work in cycling.
AB - The goal of this study was to assess the utility of experimental methods to
quantify mechanical energy expenditure (MEE) in human movement. To achieve this
goal, a theoretical model of steady-state cycling driven by individual muscle
actuators was used to produce two distinct pedal simulations. The simulations
yielded the same pedaling rate and power output, but one reduced the MEE by
avoiding eccentric muscle contractions. Contractile element force and length
change in the individual muscles was used to quantify the total positive and
negative work produced by the muscles. Three methods using external measurements
were applied to the simulated movement. The three methods to quantify MEE were
based on: (1) segment kinematic measurements, (2) work done by total joint powers
and (3) intercompensated joint powers, i.e. negative work from one joint is
transferred to an adjacent joint where energy is being generated (positive work)
via biarticular muscles. The results showed that none of the MEE analyses were
correlated to the MEE of the individual muscles, with errors reaching 40%. Errors
were mainly attributed to the inability of the MEE methods to account for co
contractions of antagonistic muscle groups. This phenomenon occurred primarily
when one muscle generated force during activation while the antagonist generated
force during deactivation.
PMID- 9645539
TI - A method to determine the 3-D stiffness of fracture fixation devices and its
application to predict inter-fragmentary movement.
AB - Inter-fragmentary movement considerably influences the fracture healing process.
Large shear movement delays while moderate axial movement stimulates the healing
process. To be able to control the mechanical situation at a fracture site and to
achieve optimal bony healing it is essential to understand the relationship
between inter-fragmentary movement, bony loading and fixation stiffness. A 6 x 6
stiffness matrix is introduced which completely describes the linear relationship
between the 6 inter-fragmentary movements and the resulting bony loading (3
forces and 3 moments). Further, it is illustrated that even in relatively stiff
external fixateur constructs simple axial loading of the bony fragments leads to
complex inter-fragmentary movement. When the 3-D stiffness description is
multiplied by the load state in sheep tibiae, movements similar to those measured
in vivo are calculated. The relationship between axial compression and medio
lateral or dorso-ventral shear varies depending on the mounting plane of the
external fixateur. The authors conclude that a single value is not sufficient to
describe the mechanical relationship between inter-fragmentary movement and bony
loading. Only a complete description of fixation stiffness allows prediction of
inter-fragmentary movement and differentiation between various configurations of
fixation devices and their potential for mechanically promoting bony healing.
PMID- 9645540
TI - In vivo knee joint loading and kinematics before and after ACL transection in an
animal model.
AB - Osteoarthritis (OA) is typically diagnosed in humans in its final stage when
joint movement becomes painful. Clinical information about the onset and the
mechanisms triggering the degenerative responses are virtually non-existent.
However, research on animal models of experimental OA shows that joint
adaptations associated with the onset of OA can be detected as early as two to
four weeks following disruption of the normal joint mechanics. Transection of the
anterior cruciate ligament (ACL) has been shown to cause OA-like symptoms in
various animal models including the cat. However. the changes in joint loading
responsible for the early tissue responses have not been quantified in vivo.
Consequently, the relationship between abnormal joint loading and the onset of OA
remains unknown. The purpose of this study was to quantify knee loading before
and early after ACL transection in the cat. Knee mechanics were assessed by
measuring patellar tendon forces, gastrocnemius forces, knee flexor and extensor
EMGs, and hindlimb kinematics before and 5, 7, and 9 days following ACL
transection in six experimental and two sham-operated animals. The knee mechanics
were not affected by sham-surgery but the muscular forces. knee extensor EMGs,
and knee range of motion were reduced following ACL transection compared to
corresponding pre-intervention values. These results suggest that ACL transection
causes a general unloading and changed kinematics of the knee. We speculate that
the decrease in loading and the altered kinematics are responsible for the onset
of biologic adaptations of the knee. Precise data about the local joint contact
mechanics before and after ACL transection are now required to further relate the
detailed changes in the knee mechanics to the early joint changes.
PMID- 9645541
TI - A kinematic and kinetic analysis of the sit-to-stand transfer using an ejector
chair: implications for elderly rheumatoid arthritic patients.
AB - Twelve elderly female rheumatoid arthritis patients (mean age = 65.5 +/- 8.6 yr)
were assessed rising from an instrumented Eser Ejector chair under four
conditions: high seat (540 mm), low seat (450 mm), with and without the ejector
mechanism operating. Sagittal plane motion, ground reaction forces, and vertical
chair arm rest forces were recorded during each trial with the signals
synchronised at initial subject head movement. When rising from a high seat,
subjects displayed significantly (p < 0.05) greater time to seat off; greater
trunk, knee and ankle angles at seat off; increased ankle angular displacement;
decreased knee angular displacement; and decreased total net and normalised arm
rest forces compared to rising from a low seat. When rising using the ejector
mechanism, time to seat off and trunk and knee angle at seat off significantly
increased, whereas trunk and knee angular displacement, and total net and
normalised arm rest forces significantly decreased compared to rising unassisted.
Regardless of seat height or ejector mechanism use, there were no significant
differences in the peak, or time to peak horizontal velocity of the subjects'
total body centre of mass, or net knee and ankle moments. It was concluded that
increased seat height and use of the ejector mechanism facilitated sit-to-stand
transfers performed by elderly female rheumatoid arthritic patients. However,
using the ejector chair may be preferred by these patients compared to merely
raising seat height because it does not necessitate the use of a footstool, a
possible obstacle contributing to falls.
PMID- 9645542
TI - Relation between the structural asymmetry of coronary branch vessels and the
angle at their origin.
AB - The relationship between the geometry of branch points on the left anterior
descending coronary artery, and the morphometry of the proximal portions of the
daughter vessels, was examined. The geometry at 23 branch points on 15 human
hearts was derived from multiplane contrast angiograms, and the morphometry at 29
sites along the daughter vessels was obtained from transverse sections using
computerized techniques. The angle of the branch at which the daughter originated
was positively correlated with the maximum thicknesses of the intima and media,
and with their circumferential asymmetry. The results suggest that large branch
angles may favor eccentric intimal thickening, a phenomenon which may predispose
to lipid accumulation and atherosclerosis.
PMID- 9645543
TI - Instantaneous moment arm determination of the cat knee.
AB - The moment arm is an important parameter for calculating forces and pressures at
a joint. Present techniques described in the literature are limited for joint
studies in animals because of the invasive procedures required which destroy the
joint integrity. This paper describes a new application of the instantaneous
helical axis (IHA) for determination of the moment arm of the knee joint without
compromising its integrity. Measurements based on the IHA technique are compared
to an established technique using six cadaveric cat hind limbs. One experiment
using the IHA technique was performed to demonstrate its application in situ. It
was found that the moment arm determined by both techniques resulted in
continuous estimations of similar magnitudes over the expected range of motion of
the knee joint, although the IHA technique is sensitive to smoothing. A trend
toward increasing moment arm as a function of increasing knee angle was observed
in four of six specimens. The in situ experiment demonstrated the ability to use
the IHA technique without compromising the integrity of the knee joint so that
further histological, morphological, or topological information could be
investigated.
PMID- 9645544
TI - En bloc staining of bone under load does not improve dye diffusion into
microcracks.
AB - Microdamage accumulation in bone has been implicated in the pathogenesis of some
bone fractures, and in implant loosening. Standard techniques for staining
microcracks may not allow all cracks to be stained. We tested the hypothesis that
crack closure in bone cortices after removal of a bending load may prevent
diffusion of stain to sites of microcrack nucleation. Following cyclic loading,
26 canine femurs were divided into a group stained en bloc while applying a four
point bending load, and another group stained without an applied load. No
differences in number or length of microcracks were observed, indicating that
crack closure does not prevent diffusion of stain to the crack location. Staining
under load is unnecessary.
PMID- 9645545
TI - Global asymptotic stability of bone remodeling theories: a new approach based on
non-linear dynamical systems analysis.
AB - Mathematical tools for the analysis of nonlinear dynamical systems are applied to
the study of stability of bone remodeling theories. As a practical application,
the same problem studied by Harrigan and Hamilton (1992) and Cowin et al. (1994b)
is analysed using these tools, and their findings on the necessary and sufficient
conditions to ensure local asymptotic stability are easily confirmed. Using a
general approach based on Lyapunov's method the same condition has been found to
be necessary and sufficient also for the global asymptotic stability, thus
confirming a result obtained by Harrigan and Hamilton (1994) by variational
methods applied to finite-element models. The proof is based on the
discretization of the spatial domain but the results for the continuum can be
easily extrapolated.
PMID- 9645546
TI - Schizophrenia and anteroventral thalamic nucleus: selective decrease of
parvalbumin-immunoreactive thalamocortical projection neurons.
AB - This study was designed to examine possible anatomical changes of thalamocortical
circuits in schizophrenics. Previous immunocytochemical studies have shown that
parvalbumin, a calcium-binding protein, occurs in thalamocortical projection
neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus
(AN). Using parvalbumin-immunocytochemistry we investigated the densities of
thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and
controls (n = 14). The densities of all neurons in the AN were estimated by Nissl
staining. The majority of thalamocortical projection neurons in AN were
identified by parvalbumin-immunoreaction. Significantly reduced densities of
thalamocortical projection neurons were estimated in the right (P = 0.003) and
left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in
right and left AN were also diminished in schizophrenics; however, these
decreases did not reach statistical significance. The reductions of parvalbumin
positive thalamocortical projection neurons were not correlated with the length
of disease, this finding supporting the neurodevelopmental etiology of structural
abnormalities in schizophrenia.
PMID- 9645547
TI - Reliability of medial temporal lobe volume measurements using reformatted 3D
images.
AB - The study assessed whether standardizing the angle of image display and
controlling for head position in three planes affects the scan-rescan reliability
of medial temporal lobe volume measures when very thin (1.5 mm) slices are used.
Five volunteers were scanned two times on consecutive days. A three-dimensional
MRI sequence acquired whole brain data in 1.4 mm thick coronal slices. The data
were displayed as 1.5 mm thick images and were rated both in the originally
acquired coronal plane, and after reformatting to correct for head tilt and
display the brain in the coronal plane perpendicular to the long axis of the left
anterior hippocampus. One rater measured five brain regions (temporal lobe,
anterior and posterior hippocampus, amygdala, and temporal horn) on the left and
right sides of the two non-reformatted and two reformatted scans to obtain inter
scan variance. Furthermore, most scans were remeasured, to obtain 'reread'
variances. All data were log-transformed in order to produce comparable
variability across brain regions of different sizes. For all the regions, except
the temporal horn, the non-reformatted scans showed significantly larger scan
rescan variability than the reformatted scans. A typical standard deviation for a
non-reformatted pair of scans was 0.10, corresponding to 26% error, while a
typical value for a reformatted pair of scans was 0.04, corresponding to 10%
error. For all the regions, the reread data (intra-rater reliability) gave
similar results for both reformatted and non-reformatted images with similar
standard deviations (typical value for reread standard deviation was 0.020,
corresponding to 5% error). The data suggest that, even when very thin slices are
acquired, volume measurement accuracy of gray matter structures in the temporal
lobe is considerably improved by controlling for image orientation in three
planes. For these structures, the sample size needed to detect a small (5%)
within-subject volume change would be halved if reformatted images were used.
Image contrast is an additional important factor since the reformatted T1
weighted images used in this study, which have suboptimal CSF/brain contrast,
worsened measurement accuracy in the temporal horn.
PMID- 9645548
TI - GABA and brain abnormalities in schizophrenia.
AB - Some recent autopsy studies indicate that gamma-aminobutyric acid (GABA) function
is decreased in brain areas that involve some of the well-described structural
changes observed in schizophrenia. The current study examined the relationship
between CSF and plasma GABA levels and brain structural measures in
schizophrenia. Sixty-two drug-free, physically healthy male patients with
schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain
structural measures on CT scans. Plasma levels of GABA were associated with
prefrontal sulcal widening and VBRs, but not global sulcal widening in the
schizophrenic patients. CSF GABA measures were not associated with brain
structural measures, but were associated with age and age of onset. The
significant relationship between plasma GABA, but not CSF GABA, and specific
brain morphology measures in schizophrenic patients suggests that if GABA
transmission is impaired in schizophrenia, it is a local, but not global,
phenomenon.
PMID- 9645549
TI - Evaluation of gender difference in regional brain metabolic responses to
lorazepam.
AB - Women are prescribed benzodiazepines twice as frequently as men and there is
evidence of differences in therapeutic responsiveness to benzodiazepines between
genders. In this study we compared the regional brain metabolic response to
benzodiazepines between male and female subjects. Sixteen healthy men and 12
healthy women were scanned with positron emission tomography (PET) and [F-18]
fluorodeoxyglucose (FDG) twice: prior to placebo and prior to lorazepam (30
microg/kg) on separate days. Lorazepam significantly and consistently decreased
whole brain metabolism and the magnitude as well as the regional pattern of the
changes was comparable for both genders (M = -4.7+/- 3 and F = -3.9 +/- 3.8
micromol/100 g/min). Lorazepam effects were largest in thalamus (- 12.5 +/- 6.2
and -8.6 +/- 7.1 micromol/100 g/min) and occipital cortex (-10.5 +/- 5.5 and
10.1 +/- 6.6 micromol/100 g/min). Lorazepam-induced changes in 'relative'
metabolism were also similar for both genders except for trend differences (0.01
< P < 0.05) in rectal gyrus, where lorazepam increased relative metabolism in
women (+4.4 +/- 9.9%) whereas it decreased in men (-3.2 +/- 8.8%, P < 0.04) and
in cerebellum, where lorazepam-induced decrements were larger in women (-5.9 +/-
6%) than in men (-1.1% +/- 6.6%, P < 0.05). There were no differences between
genders for any of the behavioral effects of lorazepam. In summary, this study
does not show differences in the response to lorazepam between the genders as
assessed by its behavioral effects and the changes in absolute metabolism; the
trend toward a difference in the relative changes in rectal gyrus and cerebellum
merits further investigation.
PMID- 9645550
TI - SPECT brain blood flow changes with continuous ligand infusion during previously
learned WCST performance.
AB - Performance of the Wisconsin Card Sorting Test (WCST) and related brain
activation patterns reflect both task learning and execution. Normal subjects
learned the WCST prior to performance during slow SPECT ligand infusion. Blood
flow increased in bilateral inferior frontal, right middle and inferior parietal
cortices. Activity decreased in hippocampi, temporal cortex, anterior cingulate
and caudate.
PMID- 9645551
TI - SPECT imaging of odor identification in schizophrenia.
AB - Deficits in olfactory identification, despite normal odor perception, are found
in some neuropsychiatric disorders, including schizophrenia. We examined if
regional cerebral blood flow (rCBF) differed between schizophrenia patients and
controls during odor identification, hypothesizing that these brain regions could
be relevant to odor identification impairments. Eight schizophrenia and eight
comparison subjects provided a baseline (picture identity matching) and
activation (odor identification) SPECT scan, obtained using 99mTc-HMPAO in a low
dose/high dose design. Six patients and seven controls had analyzable data. MEDX
data saved in ANALYZE format for SPM 95 generated paired t-test statistical data
for display in Talairach space, with rCBF changes given as Z-scores. There was no
schizophrenia vs. control group difference in rCBF for the baseline picture
matching test. For odor identification, schizophrenia patients had a
hypometabolic right-sided cortical region that included the frontal lobe Broca's
area, superior temporal lobe, and supramarginal and angular gyri. Post hoc within
group contrasts of picture-matching vs. odor identification showed that the
controls significantly increased rCBF in the right-sided inferior temporal
fusiform gyrus, and bilateral hippocampi and visual association areas for the
odor test. The schizophrenia group showed no rCBF differences for picture
matching compared to odor identification. Patients showed significant
hypometabolism in right-sided cortical areas for odor identification. They also
failed to show increased rCBF in the hippocampus and visual association area, as
seen in controls for odor identification compared to picture-matching. These
regions may be unique to schizophrenia or have broader implications for olfactory
memory retrieval.
PMID- 9645552
TI - Development of glass-ionomer cement systems.
AB - In the 1960s the idea of positive physico-chemical adhesion with tooth substance
resulted in the invention of polyacrylic acid-based cements, first the zinc
polycarboxylate and, subsequently, the glass-ionomer cements. These materials
were shown to undergo specific adhesion with hydroxyapatite and proved to have
properties satisfactory for a variety of clinical applications. The key
properties of the glass-ionomer cements--fluoride release over a prolonged period
and specific adhesion to enamel and dentine coupled with aesthetic qualities are
related to their characteristics as aqueous polyelectrolyte systems. In order to
improve toughness, speed of setting and resistance to dehydration, hybrid
materials in which some of the water content of the glass-ionomer system was
replaced by water-soluble polymers or monomer systems capable of ambient
polymerization were formulated in the late 1980s. These materials, which have
been termed resin-modified glass-ionomer cements, involve, ideally, the formation
of an interpenetrating polymer network combining the acid-base cross-linking
reaction of the metal ion-polyacid with the cross-linking polymerization of the
monomer system or additive action of the polymers. In the predominantly resin
materials there is little polyelectrolyte character and it is controversial
whether such materials should be categorized as glass-ionomer cement systems. The
specific advantages of these materials over traditional glass-ionomer systems and
over composite restorative systems remain to be fully documented. Studies of
adsorption to hydroxyapatite of typical monomers using X-ray photoelectron
spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF SIMS)
indicate that resistance to water displacement decreases as hydrophobicity
increases.
PMID- 9645553
TI - New trends in glass-ionomer chemistry.
AB - This paper surveys the different routes to develop glass-ionomer cements (GICs)
(glass polyalkenoate cements). Using a new commercially available material, Ketac
Molar, the particular ways of improving conventional GICs are described (mainly
optimizing the concentration and molecular weight of the polyacid as well as the
particle size distribution of the glass). High cross-linkage in the GIC matrix is
the key issue to achieve superior physical properties (three- body wear
resistance, compressive and flexural strength, surface hardness and solubility).
This is proven by differential scanning calorimetry and infrared spectroscopy.
PMID- 9645554
TI - Chemistry of glass-ionomer cements: a review.
AB - Studies of the setting of glass-ionomer cements have been carried out for over
twenty years, and there is now a considerable body of information concerning the
steps that lead to the conversion of a freshly mixed cement paste into a solid,
durable dental restorative. This paper reviews these studies, paying particular
attention to more recent work. The conclusion is that glass-ionomers consist of
interpenetrating networks of inorganic and organic components forming a matrix in
which particles of unreacted glass are embedded. However, there remain
uncertainties over aspects of the setting chemistry, for example over the role of
(+)-tartaric acid in the setting reaction, and over the nature of the fluoride
species which form during the reaction. The chemistry of resin-modified glass
ionomers is also discussed and shown to be more complex than that of the simple
cements. The presence of the resin component slows down the ionic cure reaction
of the conventional cement, and leads to both a significant exotherm and a set
material capable of absorbing water reversibly. The paper concludes that the
microstructure of the set cement depends completely on chemical composition and
the kinetics of the setting process, and that an understanding of the setting
chemistry of these materials is thus important for optimal clinical use.
PMID- 9645555
TI - Influence of alkali metal ions on the fracture properties of glass polyalkenoate
(ionomer) cements.
AB - The influence of substituting sodium for calcium on the properties of glass
polyalkenoate cements was investigated. Two series of glass compositions based on
PSiO2 x QAl2O3 x 0.75P2O5 x (1 - Z)CaO x XCaF2ZNa2O were studied. The fluorine
content was fixed at X = 0.50 and 0.75 and the sodium content varied by altering
Z. The glass polyalkenoate cements formed from these glasses were characterized
using a linear elastic fracture mechanics (LEFM) approach. In addition,
compressive strengths of the cements were determined. The properties of the
cements based on the high fluorine content glasses (X = 0.75) were relatively
insensitive to sodium content. The Young's modulus, un-notched fracture strength
and fracture toughness of the cements produced with the lower fluorine content
glasses (X = 0.5) reduced with sodium content, which was consistent with sodium
acting to disrupt ionic cross-linking in the polyacrylate matrix. The compressive
strength was not as dependent on sodium content as the LEFM parameters.
PMID- 9645556
TI - Fluoride release and uptake by glass-ionomers and related materials and its
clinical effect.
AB - The anticariogenic effect of silicate cement is well known and considered a
result of fluoride release. In several studies a similar fluoride release from
conventional glass-ionomer cement (GIC) has been established. Therefore, an
anticariogenic effect may be predicted from the GICs too. In my studies the
fluoride release was studied by exposing the test specimens to a continuous flow
of running tap water. At certain time periods the specimens were transferred for
1 week in a small amount of deionized water (5 ml). The determination of the
fluoride content of the solution showed the fluoride release of the material at
that time. There was an initial 'burst' effect of fluoride release and then the
release gradually decreased, settling at a constant level. The long-term release
from conventional GICs was shown to remain on the same level for at least 8
years. The amount of the constant release did not differ much between different
brands. Resin-modified GICs released fluoride to the same extent and in the
similar way as conventional GICs whereas polyacid-modified composites
('compomers') did not show an initial fluoride 'burst' effect. To study the
fluoride binding ability of GICs, specimens which had been exposed to running
water for different periods of time were treated with a 50 ppm fluoride solution.
After this 'recharging' GIC and resin-modified GIC specimens released more than
twice the amount of fluoride released before the treatment. The fluoride
treatment had no effect on polyacid-modified composites or on fluoride-containing
composites or on the amalgams. To get an impression of the clinical effect of
GICs a questionnaire was handed out to practitioners attending courses in the
Nordic countries and in Australia during the period 1991-1992 which resulted in
954 answers. Among other questions, the dentists were asked if they had observed
caries and gingival inflammation in association with GIC and composite fillings.
According to the opinion of most dentists caries and gingival inflammation had
never or only seldom been observed in association with GIC fillings whereas most
dentists had observed these complications often in connection with composite
restorations.
PMID- 9645557
TI - Fluoride release process of (resin-modified) glass-ionomer cements versus
(polyacid-modified) composite resins.
AB - The fluoride release of conventional and resin-modified glass-ionomers is
reviewed and compared to that of fluoride-releasing (polyacid-modified) composite
resins. Each formulation displays a typical fluoride release profile. The
cumulative amount of fluoride released is described by [F]c = [F](I)t/(t + t1/2)
+ beta square root t for glass ionomers whether resin-modified or not, whereas
for composite resins this quantity is given by [F]c = [F](I)t/(t + t1/2) + alpha
t. Both equations indicate that two kinetic processes are responsible for the
fluoride release profiles. The kinetic parameters [F](I), t1/2, beta and alpha
depend on the formulation. On the basis of the exchange characteristics for
fluoride, an attempt is made to explain the mechanisms responsible for these
fluoride release processes.
PMID- 9645558
TI - Resin-modified glass-ionomers.
AB - This paper reviews the current status of resin-modified glass-ionomers and
presents the results of recent findings of research in some key areas. The debate
on nomenclature pertaining to these products is perceived as being pointless and
the need for application-based ISO standards is raised. Setting characteristics
are similar in many respects to those of light-activated composites, although
some products have limited working time due to the influence of the acid-base
setting reaction and sensitivity to ambient light. Water absorption and swelling
are generally very high. The clinical significance of swelling after water
exposure is unknown. Mechanical properties of most materials lie between those of
the composites and conventional glass-ionomers depending upon the resin content
of the matrix phase of the set material. Some products demonstrate an inherent
adhesion to enamel, although etching may be required in order to make the bond
clinically effective. Bonding to dentine is probably through a more complex
mechanism than that involved with conventional glass-ionomers. Conditioning and
priming of dentine is often advocated. Fluoride release rates and their clinical
significance is an area which requires clarification and standardization. The key
factor appears to be the frequency with which the storage water is changed.
Equilibration is reached within minutes for some materials and their true
fluoride-releasing potential can only be judged under dynamic test conditions.
PMID- 9645559
TI - Compomers: between glass-ionomer cements and composites.
AB - The term 'compomer' was crafted by the producers of the first commercial material
of this kind: a polyacid-modified composite resin, sold as a filling material for
some specific applications. This term should recall the composite resins and
glass-ionomer cements, since some features of these two generic materials are
found in the compomers. Compomers contain a bifunctional monomer, which should be
able to react with the pendant methacrylate groups of other monomers, as well as
with the cations liberated by the glass particles. Several products of this kind
are now available, and the purpose of this paper is to describe some of their
specificities and to compare their influence on the mechanical properties, water
uptake and fluoride release.
PMID- 9645560
TI - Immediate versus one-month wet storage fatigue of restorative materials.
AB - Immediate finishing is a highly desirable property of restorative materials. In
general, the resin composites, the polyacid-modified resin composites and resin
modified glass-ionomers are finished immediately after light-curing. For the
conventional glass-ionomers a waiting period of 24 h is recommended. Therefore,
the objective of this study was to investigate whether immediate finishing and
application of cyclic loading under water spray on resin-modified glass-ionomers,
a conventional glass-ionomer, a polyacid-modified resin composite and a resin
composite are reflected in their Young's modulus and fatigue resistance after 1
month wet storage compared with a control group that could mature untroubled for
1 month. From this study, it could be concluded that there is a material
dependent response on immediate finishing. For the conventional glass-ionomer,
the waiting period of 24 h is highly advisable. The resin composite suffered more
than the other test materials. A second statement is that one must be cautious by
the extrapolation of findings obtained on quasi static tests (Young's modulus)
towards dynamic properties (flexural fatigue limit).
PMID- 9645561
TI - Water sorption in resin-modified glass-ionomer cements: an in vitro comparison
with other materials.
AB - The pattern of water uptake into a polyacid-modified composite resin (compomer),
Dyract (D), was assessed using gravimetric analysis and tritiated water
absorption. The results were compared with a resin composite, Herculite (H), a
resin-modified glass-ionomer, Fuji II LC (FL), and a conventional glass-ionomer,
Fuji II (F). Samples were stored in tritiated water for periods varying between 6
h and 6 months. The resulting change in gravimetric weight and dimensions was
recorded. The tritiated water content was then assessed using liquid
scintillation counting and this was compared to the gravimetric changes. The
inherent water content of each material was also established. D and H showed a
slow steady net uptake to 3% and 1.3% weight by volume (WV) respectively at 6
months. FL showed a rapid uptake reaching 8.9% WV at 7 days and 9.3% WV at 6
months. F showed a steady, less dramatic water uptake reaching 5.3% WV by 6
months. For the glass-ionomer materials, values for gravimetric water uptake and
tritium release differed due to the ongoing acid base reaction and an increase in
firmly bound water. This phenomenon was noted in D suggesting evidence of a
similar reaction in this material.
PMID- 9645562
TI - Analysis of reactions in glass-polyalkenoate/resin systems by dielectric
impedance spectroscopy.
AB - The principles of impedance spectroscopy are surveyed, with consideration of both
low and high impedance dielectric biomaterials where the response mechanisms are
dominated, respectively, by dipolar relaxation and ionic charge migration. The
situation of dental biomaterials is considered with special reference to glass
ionomer polyelectrolyte systems and to the impedance changes that may arise in
consequence of setting mechanisms. Measurements have been conducted using both
static and frequency-dependent potentials; where appropriate, with a high
impedance interface and frequency-response analyser. Data are presented for the
control situation of poly(methyl methacrylate) (PMMA) and for a series of glass
ionomer and resin-modified glass-ionomer biomaterials. It is observed that in the
glass-polyalkenoate (G-PA) materials, ionic conduction and polarization are the
dominant factors contributing to the impedance. This contrasts with the dipolar
relaxation characteristic of PMMA. It is concluded that a more extended programme
of data-acquisition is required, where possible from a 'homologous' series of
formulations, to lay a firm foundation of mechanistic interpretation.
PMID- 9645563
TI - Biocompatibility of various light-curing and one conventional glass-ionomer
cement.
AB - The purpose of this study was to determine and to compare the cellular
compatibility of modern light-curing (lc) glass-ionomer cements (GICs) to one
conventional (co) GIC. The following materials were investigated: Ionoseal (IS,
lc) (VOCO, Germany), Vitrebond (VB, lc) (3M, USA), Compoglass (CG, lc) (Vivadent,
FL) and Ketac Fil Applicap (KF, co) (ESPE, Germany). From all GICs, equally sized
specimens (height 2 mm, diameter 5 mm) were polymerized or set according to the
instructions of the manufacturers. Various extracts of all specimens were
obtained by subsequent elutions. Human primary fibroblasts of the attached
gingiva (HGF) and permanent mouse fibroblasts (3T3) were used for the
experiments. HGF and 3T3 cells were exposed to the extracts of all materials for
48 h. Growth inhibition due to cytotoxic effects was determined by staining the
cultures with Hoechst 33342 (determination of DNA and cell vitality). It was
found that the material CG induced no growth inhibition in any of the assays.
Proliferation of HGF was not, or only slightly, inhibited by the extracts of the
materials IS and KF, whereas severe alterations were caused by the extracts of
the material VB. Growth of 3T3 cells was only moderately or slightly reduced by
the extracts of materials IS and KF respectively, but was severely or totally
inhibited by all extracts of VB. From our results we conclude that the GIC VB is
very cytotoxic and therefore may also induce alterations in vivo. All other
investigated GICs revealed excellent (CG), or good (IS, KF) cellular
compatibility.
PMID- 9645564
TI - Glass-ionomers: bioactive implant materials.
AB - Glass-ionomer cements (GICs) originally designed for use as dental materials have
a number of advantages over acrylic bone cements. These include lack of exotherm
during setting, absence of monomer and improved release of incorporated
therapeutic agents; this has resulted in the development of GICs for biomedical
applications. Major landmarks in this history are the formulation of defined
composition ionomer glasses and an improved understanding of the biological and
material properties of GICs. Following implantation, GICs can form a stable
integration with bone, and affect the growth and development of bone, both
adjacent to their surface and systemically, through an ion release mechanism. The
'non-inert' nature of this group of materials is also demonstrated by their
adverse effects on neural tissue. Successful clinical use of GICs, both as bone
cements and as preformed implants for hard tissue replacement, have been reported
in the fields of otologic surgery (Cochlear implant fixation, repair of the
tympanic chain, eustation tube obliteration and as ear ossicles), and oral and
reconstructive surgery. The use of GICs in situations where they will come into
contact with nerves or neural tissue is contraindicated.
PMID- 9645565
TI - Clinical performance of glass-ionomers.
AB - Glass-ionomers were introduced to the profession 20 years ago and have been shown
to be a very useful adjunct to restorative dentistry. Their major advantages
include the ion exchange adhesion to both enamel and dentine and a continuing
fluoride release throughout the life of the restoration. The chemistry of the
setting reaction is essentially an acid/base reaction but recent research has
introduced variations in an effort to improve clinical handling. Small additions
of resin increase the physical properties to a degree and allow for a light
initiated setting mechanism. However, it is essential that the acid/base reaction
remains dominant if the full advantages of the glass-ionomer are to be retained.
The material has multiple uses in dentistry and it shows a high degree of
biocompatibility to the pulp and surrounding soft tissues. The main limitation at
this time is a relatively low fracture resistance but it is possible to protect
it through lamination with stronger materials if the need arises. This paper
examines the essential parameters for successful clinical placement and comments
on its longevity.
PMID- 9645566
TI - Confocal microscopic observation of structural changes in glass-ionomer cements
and tooth interfaces.
AB - This study aimed to develop techniques to allow dynamic imaging of a cavity
before, during and after placement of glass-ionomer restorative materials.
Cavities were cut in recently extracted third molars and the teeth longitudinally
sectioned. Each hemisected tooth surface was placed in green modelling compound
at 90 to the optical axis of the microscope. The cavity surface was imaged using
a video rate confocal microscope in conjunction with an internally focusable
microscope objective. The sample on the stage was pushed up to the objective lens
which 'clamped' the cover glass onto it. Water, glycerine or oil was placed below
the coverglass, with oil above. Internal tooth structures were imaged by changing
the internal focus of the objective. The restorative material was then placed
into the cavity. Video images were stored either onto video tape or digitally,
using a frame grabber, computer and mass memory storage. Software controls
produced time-lapse recordings of the interface over time. Preliminary
experiments have examined the placement and early maturation of conventional
glass-ionomer cements and a syringeable resin-modified glass-ionomer cement.
Initial contact of the cement matrix and glass particles was visible as the
plastic material rolled past the enamel and dentine, before making a bond.
Evidence for water movement from the dentine into the cement has also been seen.
After curing, the early dimensional changes in the cements due to water flux were
apparent using the time-lapse facility. This new technique enables examination of
developing tooth/restoration interfaces and the tracking of movement in
materials.
PMID- 9645567
TI - Bonding orthodontic brackets with glass-ionomer cement.
AB - This is a clinical paper outlining the experience of an enthusiastic group of
seven individuals in different local orthodontic practices who, over a period of
six years, have bonded some 99% of the metal orthodontic brackets to tooth enamel
using glass ionomer cement (GIC). Up until recently GIC has been little used
within the orthodontic world for the cementing of orthodontic brackets, composite
resin being the conventional adhesive. We use GIC as a bracket adhesive because
there is a very low incidence of tooth enamel decalcification occurring around
the brackets with its use compared with the more universally used composite resin
adhesives. This paper details the perceived clinical advantages and
disadvantages, and then defines the three critical areas for successful bonding
with GIC, followed by a description of the chairside technique.
PMID- 9645568
TI - Busulfan, cyclophosphamide and total body irradiation as conditioning for
allogeneic bone marrow transplantation for acute and chronic myeloid leukemia.
AB - Fifty patients with acute myeloid leukemia (AML) or chronic myeloid leukemia
(CML) underwent allogeneic bone marrow transplantation between October 1988 and
January 1997. Patients received 8 mg/kg of busulfan (BU) with 120 mg/kg of
cyclophosphamide (CY) followed by 10 Gy of total body irradiation (TBI). Twenty
consecutive patients with AML in first remission (n = 9) or CML, in chronic phase
(n = 11) entered the study (group I). Thirty consecutive patients with advanced
myeloid malignancies including AML (n = 19) and CML (n = 11) also entered the
study (group II). The probability of leukemia-free survival at 5 years was 85%
for group I patients and 50% for group II patients. Severe regimen-related
toxicities occurred in 16% of patients (two in group I, six in group II). The
most common sites affected by severe toxicities were lung (n = 6), liver (n = 2)
and heart (n = 2). The relapse rate was higher for patients allografted in
advanced stages of disease (O% at 5 years for group I and 28% for group II).
These results suggest that BU + CY + TBI is a very effective conditioning regimen
in patients with myeloid malignancies.
PMID- 9645569
TI - Big BU/CY is associated with a favorable long-term outcome in patients
allotransplanted for chronic myelogenous leukemia in chronic phase.
AB - Twenty-six adult patients, median age 36 years (range 21-53) with chronic myeloid
leukemia in first chronic phase were allotransplanted between October 1989 and
May 1995. The preparative regimen consisted of busulphan 16 mg/kg and
cyclophosphamide 200 mg/kg (big BU/CY). Cyclosporin A and methotrexate were used
for GVHD prophylaxis. Twenty-two donors were HLA-identical siblings and four
donors were mismatched for one antigen of class I. The global incidence of acute
GVHD was 50%, that of severe aGVHD (grades 3-4) was 11%; the global incidence of
chronic GVHD was 30%. No patients developed veno-occlusive disease of the liver
or interstitial pneumonia. Five patients died, one of relapse, four of transplant
related causes, mostly related to aGVHD; thus, the transplant-related mortality
was 16%. Twenty-one patients are alive, in remission, with a median follow-up of
55 months (range 24-90); actuarial probability of survival is 78% (CI 64-96). Our
study shows that this conditioning regimen is relatively easy to administer and
seems to be as effective as, if not superior to, regimens containing TBI, in
patients with chronic myeloid leukemia in chronic phase and the transplant
related mortality is not excessive even in older patients.
PMID- 9645570
TI - G-CSF serum pharmacokinetics during peripheral blood progenitor cell
mobilization: neutrophil count-adjusted dosage might potentially improve
mobilization and be more cost-effective.
AB - The optimal dosing schedule of G-CSF for peripheral blood progenitor cell (PBPC)
mobilization is still under investigation although many centers use 10
microg/kg/day in a single subcutaneous dose. However, G-CSF clearance increases
with increasing absolute neutrophil count (ANC). Hence a G-CSF dosage adjusted to
ANC might be a reasonable approach. We measured G-CSF trough serum levels by
sandwich ELISA assay at different ANCs in eight patients undergoing treatment
with filgrastim at 10 microg/kg/day in a single subcutaneous dose. A total of 26
samples were analyzed, and a strong correlation between increasing ANC and
decreasing G-CSF levels was found by linear regression analysis (P < 0.0003, r2 =
0.4199). For ANC values above 5000/microl the trough serum levels, ie 24 h after
administration, were consistently below the level that provides maximal
clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF
measurements performed in three patients at 0, 3, 6, 9 and 24 h after G-CSF
administration, showed a reduction of the area under the curve (AUC) with
increasing ANC. For an ANC of 20000/microl or greater, the G-CSF serum level fell
under the maximal in vitro stimulation threshold of 10 ng/ml within 12 h. This
preliminary pharmacokinetic data seems to suggest that an ANC-adjusted G-CSF
dosing schedule might improve the design of PBPC mobilization regimens.
PMID- 9645571
TI - Detection of maternal DNA in umbilical cord blood by polymerase chain reaction
amplification of minisatellite sequences.
AB - One of the concerns about the use of cord blood as a source of hematopoietic stem
cells for allogeneic transplantation is the possibility of contamination by
maternal cells which could cause life-threatening GVHD. We have assessed cord
blood contamination using PCR analysis of several minisatellite regions to detect
maternal DNA. Eighty mother-cord pairs were obtained for this study. In one case
there were no specific maternal alleles at any loci and, therefore, cord blood
could not be evaluated. Thus, there was a total of 79 informative cases for the
detection of maternal cells in the fetal circulation. In most cases, the level of
detection was between 0.5 and 1%. We detected maternal DNA in the cord blood
sample in only one case (1.26%), and the analysis of dilution experiments led to
an estimate of 0.5-1% maternal cells. In conclusion, using PCR amplification of
hypervariable regions, maternal DNA is very rarely detected in the cord blood
collected at birth, although this approach has a relatively low level of
sensitivity.
PMID- 9645572
TI - Long-term follow-up after high-dose therapy for high-risk multiple myeloma.
AB - Between 1985 and 1990, 133 patients with advanced multiple myeloma (MM) (74%
resistance; 41% resistant relapse, RR) were treated with five high-dose therapy
(HDT) regimens including: melphalan < or =100 mg/m2 (MEL 100) (46 patients); MEL
100 plus GM-CSF (24 patients); MEL 140 plus autologous bone marrow
transplantation (ABMT) (eight patients); MEL 140 plus TBI 850 cGy plus ABMT (37
patients); and thiotepa 750 mg/m2 (THIO 750) + TBI 850 cGy plus ABMT (18
patients). The median follow-up of alive patients as of December 1997 was 9
years. Overall, 17% experienced treatment-related mortality within 60 days (TRM)
and 12% achieved stringently defined complete remission (CR) with a median
duration of 16 months; four of 16 patients (25%) remain in CR at 10 years. The
median durations of event-free survival (EFS)/overall survival (OS) were 6/15
months. Superior EFS/OS were noted with MEL 100 plus GM-CSF and the two TBI
containing regimens (9/24 months among 79 patients) compared to the remaining 54
patients receiving MEL < or =100 or MEL 140 plus ABMT (3/5 months) (P =
0.0001/0.0001, respectively). Multivariate regression analyses (MVA) were
performed so that, despite patient heterogeneity among the five treatment groups,
potentially relevant disease, host, treatment, and supportive care variables
could be identified that were associated with TRM, CR, EFS and OS. TRM was higher
with creatinine >2.0 mg/dl, absence of ABMT/GM-CSF support and age >50 years; CR
was superior with TBI-containing regimens and < or =12 months of prior therapy;
EFS and OS both were longer with B2M < or =2.5 mg/l, age < or =50 years, absence
of RR and with ABMT/GM-CSF support. In the presence of >2 favorable variables (32
% of patients), median EFS/OS durations of 18/48 months were observed which
progressively declined with 2 and <2 favorable parameters to 6/11 months (28% of
patients) to 3/5 months (40% of patients) (P = 0.0001/0.0001). At 10 years, 10
and 20% of patients with >2 favorable variables were event-free and alive, which
was also true for the 37 patients receiving MEL 140 plus TBI. To appreciate
possible long-term contributions of supportive care or treatment intensity,
landmark analyses performed at 1, 2, 4 and 6 months revealed virtually identical
ranking orders of prognostically favorable variables to those seen pre-HDT; once
supportive care was accounted for, regimen intensity with added TBI did not
emerge as an independent favorable feature.
PMID- 9645573
TI - First and second apheresis in patients with multiple myeloma: no differences in
tumor load and hematopoietic stem cell yield.
AB - Autologous peripheral blood stem cells (PBSC) are now widely used to support
myeloablative therapy in patients with multiple myeloma (MM). The presence of
malignant cells in these autografts has been demonstrated. Characteristic
kinetics with differential and concomitant mobilization of CD34+ and malignant
cells after high-dose (HD) chemotherapy and hematopoietic growth factor
administration have been reported. We determined the amounts of tumor cells and
PBSC in leukapheresis products (LP) collected on day 1 (LP1) and 2 (LP2) from 16
MM patients harvested after HD chemotherapy and G-CSF. Furthermore, LP from six
patients collected on day 5 (LP5) could be examined. The content of clonotypic
cells was quantitated by an allele-specific oligonucleotide (ASO)-PCR assay based
on limiting dilutions. CD34+ PBSC were determined by flow cytometry. The
percentages of malignant cells in the leukapheresis products were in the range of
0% to 0.713% (mean 0.047%). CD34+ cells ranged between 0.06% and 5.4% (mean
1.23%). Comparing LP1 with LP2, no differences in the quantity of tumor cells
(mean 0.0538% vs 0.0448%; P = 0.96) and CD34+ cells (mean 1.49% vs 1.33%; P=
0.50) were seen. The calculated number of tumor cells per CD34+ cell did not
differ significantly (mean 0.0420 vs 0.0249; P = 0.65). Analyzing LP5 revealed no
changes in the number of tumor cells per CD34+ cell (0.0511 vs 0.1044; P = 0.46)
indicating a relatively constant ratio of PBSC to tumor cells during the course
of PBSC harvesting. These results offer the possibility of combining LP harvested
over several days without increasing the tumor load per CD34+ cell.
PMID- 9645574
TI - High-dose chemotherapy in patients with breast cancer: evaluation of infusing
peripheral blood stem cells containing occult tumor cells.
AB - The purpose of this study was to evaluate the frequency of detecting occult tumor
cells in peripheral blood stem cell (PBSC) harvests and to determine the impact
of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral
blood stem cell harvests from 223 patients with breast cancer were examined by an
immunocytochemistry (ICC) method for detection of occult tumor cells, and infused
after HDC without consideration of test results. Two hundred and four patients,
114 with stage II-III and 90 with stage IV disease who received only PBSC, that
were tested by ICC were evaluated for time to relapse. Five hundred and eighty
one of 619 PBSC harvests (94%) from 223 patients were tested. Fifty-three of 581
harvests (9%), 8% from stage II-III and 10% from stage IV patients, were positive
by ICC (P = 0.68). Forty-one of 223 patients (18%), 17/122 (14%) with stage II
III and 24/101 (24%) with stage IV disease, had positive harvests (P = 0.06).
Eleven percent of patients who had 1-2 harvests tested were positive as compared
to 32% of patients who had > or =3 PBSC harvests tested (P < 0.001). Nineteen
patients who were infused with a mixture of ICC negative and untested PBSC
harvests were excluded from analyses of relapse. The probabilities of relapse at
18 months for the 97 patients with stage II-III disease infused with ICC-negative
and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48).
The probabilities of relapse at 18 months for patients achieving a CR or a CR in
non-bone sites and improvement in bone lesions were 0.55 for the ICC-negative
group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was
concluded that occult tumor cells were detected by ICC in PBSC harvests from a
relatively small fraction of women with breast cancer, but were not associated
with a significant increase in the probability of early relapse or progression
when infused after HDC.
PMID- 9645575
TI - Association of pulmonary function testing abnormalities and severe veno-occlusive
disease of the liver after marrow transplantation.
AB - We investigated an association between pulmonary function testing (PFT) before
bone marrow transplantation and the development of severe veno-occlusive disease
(VOD) of the liver. We previously noted that reductions in diffusing capacity of
the lung for carbon monoxide (corrected for hemoglobin) (D(L)COc) were associated
with mortality after transplantation, but this was not caused by respiratory
failure. We performed a case-series review of prospectively collected data from
307 marrow recipients who underwent PFT within 2 weeks of transplantation. Of
these, 170 (56%) developed VOD; 39 (13%) mild, 81 (26%) moderate, and 50 (16%)
severe or fatal. Both total lung capacity (TLC) and D(L)COc were associated with
severe VOD in univariate analysis (P = 0.006 for each). However, D(L)COc entered
logistic regression models that contained variables for all known risk factors
for severe VOD, while TLC did not contribute additional predictive information.
The odds ratio (OR) associated with a D(L)COc below the lower limits of normal
(70% of predicted) was 2.4 (95 % CI, 1.0 to 5.4; P = 0.04). We conclude that
reduced diffusion capacity of the lung measured before marrow transplantation is
an independent risk for severe hepatic VOD. We speculate that the decreased
D(l)COc indicates pre-existing systemic endothelial cell damage and a
susceptibility to severe hepatic injury from chemotherapy.
PMID- 9645576
TI - Incidence and influence of GB virus C and hepatitis C virus infection in patients
undergoing bone marrow transplantation.
AB - Markers of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought in 80
patients before and after they underwent BMT in a metropolitan hospital in Tokyo
between 1990 and 1996. RNA of GBV-C was detected in 14 (18%) patients before BMT.
Of the 55 patients who had been transfused, 14 (25%) possessed GBV-C RNA at a
frequency significantly higher than in the 25 untransfused patients who were all
negative (P < 0.01). HCV RNA was detected in three of the 55 (5%) transfused
patients, but in none of the 25 untransfused patients. Sera at 3 months after BMT
were available for 57 patients. GBV-C RNA persisted in all 10 patients who were
infected before BMT, while it was detected in five of the remaining 47 (11%)
patients who were not. However, persistent and/or ongoing GBV-C infection had no
appreciable influence on patient morbidity or mortality. Two of the 57 patients
were positive for HCV RNA before BMT and this persisted after BMT in both. HCV
RNA became positive in eight of the remaining 55 (15%) patients who were negative
before BMT. Of the 14 patients who received transfusions screened by the first
generation test at BMT, seven (50%) became positive for HCV RNA, a rate
significantly higher than the one of 41 (2%) patients who received transfusions
screened by the second-generation test (P < 0.001). These results indicate that
BMT patients are at increased risk of GBV-C infection transmitted by transfusions
received before and at the time of BMT, and that the risk of HCV infection has
decreased after the implementation of the second-generation anti-HCV test.
PMID- 9645577
TI - Unique risk factors for bacteraemia in allogeneic bone marrow transplant
recipients before and after engraftment.
AB - A study of the risk factors associated with bacteraemia in 191 allogeneic bone
marrow transplant (BMT) recipients (1991-1996) was performed. In contrast to risk
factors commonly cited for cancer chemotherapy, mucositis, degree of conditioning
toxicity of the gut and lungs, duration of neutropenia, and severity of
neutropenia and monocytopenia were not associated with bacteraemia in the pre
engraftment period, during which the only significant risk factor was late stage
underlying disease (P < 0.05). After engraftment, Hickman catheter infection, and
severe acute and chronic graft-versus-host disease (GVHD) were found to be
independently associated with bacteraemia by multivariate analysis (P < 0.001,
<0.05 and <0.05, respectively). This might be explained by intense antimicrobial
prophylaxis, early empirical treatment, and non-routine use of haemopoietic
growth factors. No significant difference in mortality was detected between
bacteraemic and non-bacteraemic patients in both periods. Allogeneic BMT
recipients are therefore a group of patients distinct from other cancer patients
receiving chemotherapy at risk of developing bacteraemia. The study findings
prompt consideration of a management protocol incorporating early and routine use
of haemopoietic growth factors before engraftment in high-risk patients with late
stage underlying malignancies, routine antimicrobial prophylaxis for acute GVHD
with intense immunosuppression, and intravenous immunoglobulin therapy for
chronic GVHD. Further cost-benefit analyses are warranted.
PMID- 9645578
TI - Safety and efficacy of spinal vs general anaesthesia in bone marrow harvesting.
AB - Bone marrow harvesting (BMH) can be performed with either general (GA) or spinal
anaesthesia (SPA). Whether SPA is advantageous in BMH and if this technique is
safe for procedures performed in the prone position is still controversial. To
evaluate the safety and efficacy of both anaesthetic techniques in BMH, 37
allogeneic donors (nine female, 28 male; 34.3 +/- 9 years; ASA class 1-2)
received either spinal (group 1, n =20) or general anaesthesia (group 2, n = 17)
according to their personal wishes. Under standardised harvesting conditions,
haematology parameters, cell counts (MNC, CD34+), haemodynamic parameters,
adverse reactions and patient satisfaction were registered. No differences were
seen between groups with respect to demographic data, harvesting time (55 +/- 17
vs 60 +/- 16 min) and bone marrow cell counts (MNC: 6.68 +/- 2.1 vs 5.7 +/- 1.7
ml/10(6)). The incidence of hypotension was higher in group 1 (45 vs 10.8%; P
=0.042). Postoperative analgesic requirement and emesis were increased in group 2
(P < 0.04) in comparison to group 1. In conclusion, the present study failed to
show superiority of spinal over general anaesthesia with regard to the quality of
the harvested bone marrow. However, the lower incidence of complaints after
spinal anaesthesia appears to offer an advantage over GA in healthy allogeneic
bone marrow donors.
PMID- 9645579
TI - Routine fluoroscopic guidance is not required for placement of Hickman catheters
via the supraclavicular route.
AB - The purpose of this study was to evaluate the efficacy and safety in placement of
Hickman catheters via the supraclavicular route without fluoroscopic guidance. We
studied 81 consecutive percutaneous placements of dual lumen Hickman catheters
via the supraclavicular route without the use of fluoroscopic guidance. Success
rates, technical problems, complications, infections and reasons for explantation
were recorded prospectively. Seventy-nine punctures were successful (97.5%). One
pneumothorax (1.2%) and three accidental arterial punctures (3.7%) occurred.
Difficulties in introducing the catheter through the peel away sheath or
misplacement were not observed. The catheters remained in place for a total of
7657 days (mean 94.5, range 3-392 days). Sixteen blood cultures were positive
(2.1/1000 catheter days). Five catheters (6.1%) were lost because of mechanical
complications. Forty-two lines (52%) were removed electively, 23 (28.4%) because
of suspected infection, and two (2.5%) because of tunnel infection. Nine patients
died with a functioning catheter. We conclude that the supraclavicular approach
to the subclavian vein is safe and efficient for introduction of Hickman
catheters. Using this access, routine fluoroscopic or sonographic guidance is not
required for proper placement. Implantation of the lines in an intensive care
unit did not lead to higher infection rates than those reported in the
literature.
PMID- 9645580
TI - Pneumoperitoneum without peritonitis after allogeneic peripheral blood stem cell
transplantation.
AB - Allogeneic blood stem cell transplantation is associated with multiple
complications. We report a case of pneumoperitoneum without peritonitis
associated with colonic pneumatosis in a patient who had undergone an allogeneic
peripheral blood cell transplant
PMID- 9645581
TI - Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated
lymphoproliferative disorder of the brain.
AB - EBV-associated lymphoproliferative disorder (LPD) is a rare but serious
complication in marrow transplant recipients. A 31-year-old Japanese woman in the
second chronic phase of CML received an allogeneic BMT from her HLA 2-locus
incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the
right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two
courses of donor lymphocyte transfusions (DLT) of 10(6)CD3+ T cells/kg of body
weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient
died of recurrent blastic crisis of CML. This case suggests that DLT may be
ineffective for the treatment of CNS EBV-LPD.
PMID- 9645582
TI - Acquired ichthyosis associated with chronic graft-versus-host disease following
allogeneic peripheral blood stem cell transplantation in a patient with chronic
myelogenous leukemia.
AB - Acquired ichthyosis (AI) has rarely been described following bone marrow
transplantation (BMT). We report a 29-year-old male, who underwent allogeneic
peripheral blood stem cell transplantation (alloPBSCT) for chronic myelogenous
leukemia, and who developed AI associated with chronic graft-versus-host disease
(cGVHD). Both of these disorders were treated successfully with cyclosporin A. We
conclude that AI may be related to an autoimmune process on the basis of cGVHD,
and dermathopathologic evaluation must be performed in patients with skin changes
suggesting AI following allogeneic bone marrow transplantation.
PMID- 9645583
TI - Graft-versus-myeloma after donor leukocyte infusion: maintenance of marrow
remission but extramedullary relapse with plasmacytomas.
AB - Adoptive immunotherapy with donor leukocytes has emerged as a promising strategy
for the treatment of myeloma recurrence after allogeneic transplantation. 2.9 x
10(8)/kg donor mononuclear cells containing 1.4% CD34+ and 37% CD3+ cells were
administered to a 48-year-old patient with non-secretory plasmablastic myeloma
relapsing 9 months after a blood stem cell transplant from his HLA-identical
sibling. In view of the extensive marrow infiltration and the aggressive
behaviour of the disease, the donor cells were preceded by a course of EDAP
chemotherapy. There was rapid clinical improvement, and CR was achieved on day 30
post infusion. However, three subcutaneous plasmacytomas showing anaplastic
features developed within a few days. These failed to respond to interferon-alpha
and continued to grow for 5 weeks in the absence of marrow plasmacytosis or other
evidence of systemic disease. Grade 3 acute liver GVHD developed on day 79 which
was controlled with immunosuppression. Overt systemic relapse occurred on day 90
as the GVHD came under control. The course of our case suggests highly
proliferative malignant cells may escape the graft-versus-tumour effect of
immunocompetent allogeneic cells in extramedullary sites subsequently resulting
in overt systemic relapse if left untreated. New approaches are needed to deal
with the problem of extramedullary disease recurrence.
PMID- 9645584
TI - Flow cytometry comparison of CD34+ subsets in bone marrow and peripheral blood
after priming with glycosylated or non-glycosylated rhG-CSF.
PMID- 9645585
TI - Treatment of patients with malignant lymphoma with Mini-BEAM reduces the yield of
CD34+ peripheral blood stem cells.
PMID- 9645586
TI - Heat shock proteins in inflammation and asthma: Dr Jekyll or Mr Hyde?
PMID- 9645587
TI - Epithelial repair in asthma. Do the benefits of house dust mite avoidance result
from proteinase avoidance?
PMID- 9645588
TI - What causes airway remodelling in asthma?
PMID- 9645589
TI - Exposure-response relationships of occupational inhalative allergens.
AB - Only a few threshold limit values exist at present for allergens in the workplace
known to cause bronchial asthma. This contrasts with the great number of
occupational asthma cases observed in industrialized countries. Recently
published studies provide clear evidence for exposure intensity response
relationships of occupational allergens of plant, microbiological, animal or man
made origin. If allergen exposure levels fall short of determined limit values,
they are not associated with an increased risk of occupational asthma.
Corresponding data are available for wheat flour (1-2.4 mg/m3), fungal alpha
amylase (0.25 ng/m3), natural rubber latex (0.6 ng/m3), western red cedar (0.4
mg/m3) and rat allergens (0.7 microg/m3). It is suggested to stipulate legally
binding threshold limit values (TLV/TWA) on this basis in order to induce more
effective primary preventive measures. If no reliable data on the health risk of
an occupational airborne noxa exist, the lowest reasonably practicable exposure
level has to be achieved. Appropriate secondary preventive measures have to be
initiated in all workplaces contaminated with airborne allergens. Verified
exposure-response relationships provide the basis for risk assessment and for
targeted interventions to reduce the incidence of occupational asthma also in
consideration of cost benefit aspects. 'Occupational asthma is a disease
characterized by variable airflow limitation and/or airway hyperresponsiveness
due to causes in a working environment. These causes can give rise to asthma
through immunological or non-immunological mechanisms. Up to 15% of all asthma
cases are of occupational origin or have at least a significant causal
occupational factor. According to the New Zealand part of the European
Respiratory Health Survey, an increased risk of asthma prevalence was found for
several occupations such as laboratory technicians, food producers, chemical
workers, plastic and rubber workers. The Spain part of this study comprising 2646
Spanish subjects showed an asthma risk to be attributed to occupational exposures
between 5 and 6.7%. Main asthma-inducing agents in the workplace are flour, grain
and feed dust, animal dander/urinary proteins and isocyanates. Further, several
inhalative irritants such as chlorine, acid or alkaline aerosols play a pivotal
role. Many low molecular weight chemicals have irritative as well as allergenic
effects on the airways, e. g. isocyanates and acid anhydrides. In addition to
chronic or repetitive exposures, also singular accidental exposure to high
concentrations of irritative or toxic airborne substances can cause occupational
asthma. This condition is frequently called reactive airways dysfunction.
PMID- 9645590
TI - Hypothalamic-pituitary-adrenal function in children with asthma and rhinitis
treated with topical glucocorticosteroids.
AB - BACKGROUND: The risk of suppression of hypothalamic-pituitary-adrenal (HPA)
function in children on topical glucocorticosteroids is currently much debated.
OBJECTIVE: To review data on HPA function in children with asthma and rhinitis on
topical glucocorticosteroids, and to discuss the value of HPA function measures
in clinical practice and research. METHOD: A review of peer refereed data.
RESULTS/CONCLUSIONS: There is no evidence that insufflated or inhaled
glucocorticosteroids in recommended doses have ever caused clinically significant
HPA insufficiency in any child. Using sensitive measures of basal adrenal
activity, however, several studies have found suppressive effects with specific
drugs, high doses and application systems. These observations may represent
homeostatic diminution in endogenous cortisol. Such measures have no place in the
management of children on topical glucocorticosteroids, but may be useful in
clinical trials assessing systemic activity of administration regimens and
application devices. In children growth suppression seems to the most important
adverse effect of topical glucocorticosteroids.
PMID- 9645591
TI - Heat shock protein 70 upregulation is related to HLA-DR expression in bronchial
asthma. Effects of inhaled glucocorticoids.
AB - BACKGROUND AND OBJECTIVE: Antigen processing determines the production of
peptides from antigens - including allergens - and their binding to class II
major histocompatibility complex molecules, that stimulate T-cell responses. Heat
shock protein (hsp) 70 are recognized to have a role in chaperoning antigenic
peptides and in facilitating class II peptide assembly. We studied the HLA-DR and
hsp70 expression on BAL cells and bronchial biopsies from asthmatics, as well as
the effect of low dose fluticasone propionate treatment. METHODS: Twenty-three
asthmatics and eight normal subjects were selected. In each subject BAL and
bronchial biopsies were performed. Eighteen out of 23 asthmatics, underwent the
second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate
treatment (250 microg b.d.) in a placebo-controlled double-blind study. BAL fluid
and biopsies were processed to evaluate HLA-DR and hsp70 expression by
immunochemistry methods. RESULTS: Hsp70 and HLA-DR upregulation was present on
professional and non-professional antigen presenting cells (APCs). In asthmatics,
the hsp70 and HLA-DR expression was higher in BAL (hsp70 P<0.001, HLA-DR P<0.001)
and bronchial epithelium (hsp70 P<0.001, HLA-DR P<0.001) when compared with
controls. We also observed a significant correlation between hsp70 and HLA-DR
expression in BAL (P<0.005) and epithelium (P<0.001). Fluticasone propionate
treatment down-regulated the hsp70 and HLA-DR expression in BAL (hsp70 P < 0.001,
HLA-DR P < 0.05) and bronchial epithelium (hsp70 P < 0.05, HLA-DR P < 0.05). A
serial section comparison study showed that CD1a+ cells and macrophages were
positive for both hsp70 and HLA-DR in the submucosa. CONCLUSIONS: Our results
support the hypothesis that hsp70 over-expression implies a potential role for
these proteins in antigen processing and/or presentation resulting in an
increased activity of APCs, which is essential for the initiation and modulation
of the asthmatic immune response in chronic asthma. Fluticasone propionate
induces downregulation of HLA-DR and hsp70 molecules thus regulating inflammation
by affecting key mechanisms of the allergic response.
PMID- 9645592
TI - Mite-antigen avoidance can reduce bronchial epithelial shedding in allergic
asthmatic children.
AB - BACKGROUND: Asthma is characterized by bronchial hyperresponsiveness (BHR),
bronchial mucosa inflammation and airway epithelial damage. OBJECTIVE: This study
was designed to evaluate the effect of mite avoidance on bronchial epithelial
shedding in asthmatic children sensitized to Dermatophagoides. METHODS: The
percentages of airway epithelial cells and eosinophil have been counted in
samples obtained by hypertonic saline-induced sputum before and after a period of
antigen avoidance in an Alpine environment (1756 m). The degree of bronchial
hyperresponsiveness to methacholine was also evaluated. RESULTS: After avoidance
the median (lower, Q1, and upper, Q3, quartile) percentage of epithelial cells in
the sputum decreased significantly from 3.50 [0.50;6.98] to 0 [0;0.5] (P=0.012)
and eosinophil percentage decreased from 1 [0;5.25] to 0 [0,1.5] (P<0.05). Median
(Q1,Q3) PC20 increased significantly from 2.75 [1.53;7.5] to 3.25 [1.65;15.25]
mg/ mL (P=0.038). After 3 weeks of re-exposure to mite the epithelial median
(Q1,Q3) percentage raised to 3.90 [1.5;6] (P = 0.027), eosinophils to 1.5
[0;3.00] (NS) and PC20 was 5.25 [1.68;14.50] (NS). CONCLUSION: Exposure to house
dust mite antigen can induce airway epithelial shedding even in subjects with low
eosinophil airway infiltration, thus supporting the idea that epithelial damage
in asthmatics sensitized to Dermatophagoides may be due to a proteolytic activity
of the mite major antigens.
PMID- 9645593
TI - Inhaled corticosteroid reduced lamina reticularis of the basement membrane by
modulation of insulin-like growth factor (IGF)-I expression in bronchial asthma.
AB - BACKGROUND: Pathological studies of bronchial biopsy specimens have confirmed the
apparent thickening of lamina reticularis of the epithelial basement membrane.
Corticosteroids have proven to be most effective in modifying airway
inflammation. However, there is not much data on the effects of corticosteroid
treatment on the basement membrane. OBJECTIVE: To investigate the effects of
inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane
and cellular infiltration into the bronchial mucosa, and the expression of growth
factors in patients with asthma. METHODS: We studied bronchial biopsies from 24
asthmatic patients before and after treatment with inhaled BDP, 400 microg twice
a day or placebo, for 6 months in a double-blind manner. Each subject recorded
daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial
responsiveness to methacholine were measured before and after treatment. The
thickness of the basement membrane was determined by electron microscopy.
Inflammatory cells and the expression of growth factors were examined by
immunohistochemistry in endobronchial biopsy specimens. RESULTS: After 6 months
of treatment, we observed a significant improvement of asthma symptoms (P<0.01),
PEF (P<0.01), diurnal variation of PEF (P<0.05), and airway responsiveness (P<
0.05) in the BDP group compared with the placebo group. This was accompanied by a
significant decrease in the thickness of the lamina reticularis (P < 0.001), and
in the number of activated eosinophils (P<0.01), T-lymphocytes (P<0.01), and
fibroblasts (P < 0.05) in BDP-treated patients. There was also a reduction in the
expression of insulin-like growth factor (IGF)-I (P < 0.01). Significant
correlation was found between the IGF-I expression and collagen thickening (rs =
0.34, P<0.01), and the number of fibroblasts (rs = 0.45, P < 0.01). CONCLUSION:
These results suggest that corticosteroid treatment in asthma can reduce the
lamina reticular thickness by modulation of IGF-I expression with consequent
inhibition of the airway infiltration by inflammatory cells, and therefore may
help to prevent remodelling of the airways.
PMID- 9645594
TI - Association of polymorphisms within the tumour necrosis factor (TNF) genes and
childhood asthma.
AB - BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a potent modulator of
immune and inflammatory responses, and has been implicated in a variety of
autoimmune diseases, including asthma. Increased levels of TNFalpha have been
detected in both sputa and bronchoalveolar lavage fluid of asthmatic subjects
during acute attacks. Interindividual variation in TNFalpha levels may be
genetically determined and polymorphisms within the TNF genes and nearby HLA
Class II region have been associated with differences in TNFalpha production.
OBJECTIVE: To investigate the association of differences in asthma-related
phenotypes with two biallelic polymorphisms: a G to A substitution at position -
308 of the TNFalpha gene promoter (TNF1 and TNF2 alleles) and an NcoI
polymorphism in the first intron of the lymphotoxin alpha gene (LT-alpha*1 and LT
alpha*2 alleles). METHODS: The regions of interest were amplified from genomic
DNA using specific primers and PCR. Dot blot analysis was used for genotyping
individuals for the TNFalpha - 308 polymorphism, while restriction enzyme
digestion was used for genotyping individuals for the LT-alpha gene NcoI
polymorphism. A case-control analysis was then performed on 74 asthmatic and 50
non-asthmatic unrelated children for each polymorphism. RESULTS: The TNFalpha -
308 TNF1 allele was present at a significantly higher frequency in cases than
controls (OR= 2.4, P=0.003), and homozygosity for the TNF1 allele was associated
with a fivefold increased risk of physician diagnosed asthma relative to the
other genotypes (OR = 5.23, P = 0.004). The LT-alpha*2 allele showed similar
associations, including an approximately fivefold higher risk of physician
diagnosed asthma for LT-alpha*2 homozygotes (OR = 4.89, P = 0.019). Evidence of a
significant linear trend in asthma risk across the three genotypes was found for
both polymorphisms. CONCLUSION: These results suggest an important role for the
TNFalpha gene or a linked locus in an inherited asthma diathesis.
PMID- 9645595
TI - Indoor environment of residential homes in Hong Kong--relevance to asthma and
allergic disease.
AB - BACKGROUND: The prevalence of asthma and allergic disease has been increasing in
Hong Kong and environmental factors are thought to play a major role. AIM: To
define the distribution of common inhaled allergens and air pollutants inside
residential homes in Hong Kong. METHODS: Forty randomly selected residential
homes were visited and surveyed. Dust samples were collected from mattress,
bedroom floor, lounge room floor and kitchen floor for assays of Der p 1, Fel d
1, and Bla g 2. Nitrogen dioxide (NO2) levels were measured by stationary
samplers left in the bedroom, lounge room and kitchen over a 1-week period.
RESULT: All 40 homes were apartments in high-rise buildings and the mean age of
the homes was 7.6 +/- 4.8 years. Visible dampness and mould patches were present
in 27.5% of homes and the main fuel for cooking was gas (97.5%). Der p 1, Fel d 1
and Bla g 2 were detectable in at least 1 niche in over 85% of homes. In
particular, all dust samples from mattress and bedroom floor contained Der p 1,
and over 50% had levels > or = 2 microg/g. The (geometric) mean Der p 1 level in
mattress dust was 8.8 (0.3-157.8) microg/g. Fel d 1 and Bla g 2 were present in
low levels throughout the homes with respective (geometric) means of 0.3 (0-3.7)
microg/g and 0.1 (0-1.1) Unit/g in mattress dust. NO2 was readily detected in all
niches but the highest level was in the kitchen with mean exposure of 48.7 ppb
which was 1.5 times higher than that in the bedroom and lounge room. CONCLUSION:
Major allergens of mite, cat and cockroach, and NO2 are present in varying
quantities in residential homes in Hong Kong. Exposure to these environmental
factors could be important in the development of asthma and allergic diseases in
susceptible individuals.
PMID- 9645596
TI - Atopy in children with otitis media with effusion.
AB - BACKGROUND: Contrasting data have been found on the prevalence of atopy in
children with otitis media with effusion (OME). A major issue would be to
determine whether screening for atopy should be recommended. Setting Centre for
Study of Otitis Media with Effusion, Tabiano Terme, Parma, Italy. OBJECTIVE: The
purpose of this study was to investigate the relation of OME to atopy. METHODS:
The subjects were 172 children with OME and a control group of 200 children. The
protocol included a questionnaire survey of diseases associated with atopy, a
skin-prick test and a clinical evaluation of allergic symptoms and
hypersensitivity to aeroallergens. RESULTS: No significant difference between
patients and control group was observed for family history of atopy or positive
skin-prick test reactions. Symptoms associated with atopy occurred significantly
more frequently in the group with OME (P<0.001), though only the presence of
rhinitis or atopic eczema was significantly associated with OME. CONCLUSIONS:
Prevalence of positive skin-prick tests results is not enhanced in children with
OME. Nevertheless, the association of OME with symptoms associated with atopy
suggests that such concomitant diseases may play a part in the pathogenesis of
the disorder. Children with allergic rhinitis or atopic eczema should be
investigated by tympanometry for OME.
PMID- 9645597
TI - Increased nitric oxide in nasal lavage fluid and nitrotyrosine formation in nasal
mucosa--indices for severe perennial nasal allergy.
AB - BACKGROUND: The nose contributes the large amount of nitric oxide (NO) to exhaled
air. NO is a mediator of vasodilation and yields peroxynitrite (ONOO-) by
reacting with superoxide (O2-). ONOO attacks tyrosine residues to form
nitrotyrosine. OBJECTIVE: The aim of this study was to examine the
pathophysiological role of NO in nasal mucosa in patients with perennial nasal
allergy. METHODS: We measured nitrite and nitrate (NO2-/NO3-) and 3',5'-guanosine
monophosphate (cyclic GMP) in nasal lavage fluid, and also measured haemoglobin
concentration in nasal mucosa as an indicator of blood volume in the patients and
healthy volunteers. The deleterious role of NO was also investigated by measuring
nitrotyrosine in nasal mucosa. RESULTS: The NO2-/NO3- concentration in the nasal
lavage fluid was 39.5+/-2.8 microM in healthy volunteers (n=40), 42.4+/-3.0
microM in patients with mild allergy (mild group, n=32), and 88.7+/-6.6 microM in
patients with severe allergy (severe group, n=61). In the patients whose symptoms
were improved with treatment, NO2-/NO3- levels decreased to 45.7+/-10.4 microM.
The concentration of cyclic GMP in nasal lavage fluid was higher in the severe
group than in the healthy volunteers. The mucosal haemoglobin index was 88+/-4 in
the healthy volunteers, 67+/-4 in the mild group, and 53+/-2 in the severe group.
The formation of nitrotyrosine was expressed 0.58+/-10% to total tyrosine in the
severe group (n=11), but was not found in non-allergy patients (n=9).
CONCLUSIONS: The production of NO was increased in patients with perennial nasal
allergy, but the blood flow in the nasal mucosa of patients was reduced.
Nitrotyrosine formation suggests that there is a process of ONOO(-)-induced
damage in mucosa of patients with the perennial nasal allergy and this damage may
limit the dilatation of blood vessels, despite the presence of excessive NO.
PMID- 9645598
TI - CD11b and L-selectin expression on eosinophils and neutrophils in blood and
induced sputum of patients with asthma compared with normal subjects.
AB - BACKGROUND: Patients with asthma show altered surface expression of the adhesion
molecules CD11b and L-selectin on airway granulocytes compared with blood
granulocytes. OBJECTIVE: To investigate whether this modulation is related to
disease activity or due to transendothelial migration, we compared the CD11b and
L-selectin expression on blood and induced sputum eosinophils and neutrophils
between patients with asthma and normal subjects. METHODS: Eleven normal subjects
(21-43 years), nine patients (21-34 years) with mild atopic asthma and 10
patients (20-47 years) with moderate to severe atopic asthma on regular treatment
with inhaled steroids underwent sputum induction by inhalation of nebulized
hypertonic saline (4.5%). CD11b and L-selectin expression on granulocytes from
blood and DTT-homogenized sputum were analysed by flow cytometry. Eosinophils
could be discriminated from neutrophils by using depolarized light scatter.
Disease activity was assessed by baseline FEV1 and airway responsiveness to
histamine (PC20). RESULTS: Sputum eosinophils showed higher expression of CD11b
(P<0.001) and lower expression of L-selectin (P<0.001) compared with peripheral
blood eosinophils. CD11b and L-selectin expression on eosinophils from blood or
sputum did not differ between the three groups. Similar results were obtained for
neutrophils. The PC20 in the patients with moderate-to-severe asthma was related
to CD11b expression on blood (R=-0.92, P=0.001) and sputum eosinophils (R=0.75,
P=0.02). CONCLUSIONS: Flow cytometry of induced sputum granulocytes from
asthmatic as well as normal subjects is feasible. We conclude that the modulated
expression of CD11b and L-selectin on airway granulocytes is not specific for
asthmatic airway inflammation, but is probably the result of tissue migration per
se. This implies that CD11b and L-selectin expression on granulocytes in induced
sputum cannot be used as marker of disease activity.
PMID- 9645599
TI - Regulation of interleukin-8 binding and function by heparin and alpha2
macroglobulin.
AB - BACKGROUND: Increased expression of interleukin-8 (IL-8), a potent neutrophil
chemoattractant, is associated with a number of inflammatory diseases.
Interleukin-8 binds to the glycosaminoglycan (GAG) heparin and the protease
inhibitor alpha2-macroglobulin, molecules which regulate the function of a number
of cytokines. Heparan sulphate was previously shown to enhance neutrophil
chemotactic responses to IL-8. OBJECTIVE: The purpose of this study was to
investigate the effect of heparin, heparan sulphate and alpha2-macroglobulin on
IL-8 binding to neutrophils and subsequent functional effects in vitro. METHODS:
The binding of 125I-IL-8 to normal neutrophils at 4 degrees C was studied and the
IL-8 induced neutrophil chemotactic response was investigated using micro-Boyden
chambers. Complexation of IL-8 with alpha2-macroglobulin was confirmed using gel
filtration chromatography. RESULTS: Heparin, but not heparan sulphate, inhibited
the binding of 125I-IL-8 to neutrophils (IC50=26 microg/mL) and IL-8 induced
neutrophil chemotactic responses (IC50=4 microg/mL). The specific inhibitory
effect of heparin was apparently due to an interaction with IL-8 which was charge
dependent, since dextran sulphate had a greater inhibitory effect on chemotactic
responses (IC50=2 microg/mL) and FITC-heparin did not bind to neutrophils. The
heparin-induced inhibition of IL-8 binding and chemotactic responses was reversed
in a dose-dependent manner in the presence of alpha2-macroglobulin. The binding
of 125I-IL-8 to neutrophils in the presence of alpha2-macroglobulin appears to
be, in part, through the specific IL-8 receptor. CONCLUSION: These results point
to an anti-inflammatory role for heparin and a novel, potentially, pro
inflammatory role for alpha2-macroglobulin which together indicate the importance
of cytokine-binding macromolecules in determining net cytokine function.
PMID- 9645600
TI - Various immunological phenotypes are associated with increased airway
responsiveness.
AB - BACKGROUND: Bronchial asthma is characterized by a TH2 type immune response,
chronic inflammation of the airways and increased airway responsiveness. The
relationship between IgE- and inflammatory-dependent mechanisms that contribute
to bronchial asthma are not well defined. OBJECTIVE: The purpose of this study
was to compare and analyse the immune pathways that resulted in development of
allergen-induced and/or inflammatory dependent increased airways responsiveness.
RESULTS: BALB/c and C57BL/6 mice responded to OVA-sensitization with elevated
allergen-specific IgE/IgG1 serum antibody-titres and the development of cutaneous
immediate-type hypersensitivity reactions. Increased airway responsiveness was
observed following airway allergen challenges. However, the inflammatory
component of the lung differed between the strains. In OVA-sensitized BALB/c mice
a marked increase in lymphocytes, eosinophils and neutrophils in BAL fluids was
parallelled with elevated production of IL-4, IL-5 and TNFalpha in the lung. In
contrast in OVA-sensitized C57BL/6 mice, the inflammatory immune response in the
lung was much weaker. We postulate that two pathways can regulate the induction
of increased airway responsiveness. One depends on the presence of allergen
specific IgE/IgG1 and allergen, and a second is mediated by allergen-independent
inflammation of the lung. To test this hypothesis, BALB/c mice were treated
nasally with low doses of bacterial superantigen (SEB) as a prototypical inducer
of airway inflammation, following which influx of lymphocytes, eosinophils and
neutrophils into the airways was parallelled by development of increased airway
responsiveness in the absence of allergen-specific IgE/IgG1 antibodies and
allergen. CONCLUSIONS: These results indicate that increased airway
responsiveness is associated with different immunological phenotypes in BALB/c
and C57BL/6 mice.
PMID- 9645601
TI - Inhibitory effect of NPC-17731 on BK-induced and antigen-induced airway reactions
in guinea-pigs.
AB - BACKGROUND: Bradykinin (BK) has been suggested to act as a mediator in the
airways in inflammatory conditions, such as asthma through the activation of B2
receptors. NPC-17731 (D-Arg0[Hyp3, D-HypE(trans-propyl)7, Oic8]BK) has potent
antagonistic activity against B2-receptors without agonistic activity. OBJECTIVE:
We have evaluated the inhibitory effect of NPC-17731 against BK in guinea-pig
airways. In addition, we have investigated the effects of NPC-17731 on antigen
induced airway responses. METHODS: Bronchoconstriction was assessed as an
increase in lung resistance (RL) and a decrease in dynamic compliance (Cdyn).
Airway plasma leakage was assessed by extravasation of intravenously injected
Evans blue dye. To estimate the effect of drugs on antigen-induced reactions,
guinea-pigs were actively sensitized by exposure to aerosol ovalbumin (OA) twice
and challenged by OA inhalation. Acute bronchoconstriction was measured for 15
min. Airway vascular leakage was measured at 10 min after the challenge.
Assessment of airway hyperresponsiveness against acetylcholine and
bronchoalveolar lavage were conducted at 18-24 h after the antigen-challenge.
RESULTS: NPC-17731 (0.3-30 microg/kg, i.v.) inhibited intravenously applied BK
induced bronchoconstriction in a dose-dependent manner. The 50% inhibitory doses
(ID50) were 1.3 microg/kg for RL and 2.8 microg/kg for Cdyn. NPC-17731 (1-10
microg/kg, i.v.) inhibited BK-induced microvascular leakage in a dose-dependent
manner (ID50 = 4.2 microg/kg). In addition, 10 microg/kg of NPC-17731 abolished
the inhaled BK-induced bronchoconstriction. In the sensitized animals, 100
microg/kg NPC-17731 significantly reduced the airway microvascular leakage and
the decrease in Cdyn induced by ovalbumin exposure (P < 0.05), but did not
influence the increase in RL. NPC-17731 (100 microg/kg) inhibited the antigen
induced airway hyperresponsiveness and the increase in eosinophils in BAL fluids.
CONCLUSION: These results indicate that NPC-17731 is a potent BK antagonist in
vivo and that BK may partially contribute to the antigen-induced airway responses
in guinea-pigs.
PMID- 9645602
TI - Inhaled procaterol inhibits histamine-induced airflow obstruction and
microvascular leakage in guinea-pig airways with allergic inflammation.
AB - BACKGROUND: Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit
airway microvascular leakage in experimental animals. This effect may change in
animals with chronic airway inflammation. OBJECTIVE: We examined whether inhaled
beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic
allergic inflammation. METHODS: Three weeks after the sensitization with
ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a
day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled
vehicle for OA (saline) for 3 weeks. One day after the last challenge, different
doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to
animals for 10 min after an anaesthesia. Fifteen minutes after the end of
inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a
marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or
vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6
min and the lungs were removed to calculate the amount of extravasated EB dye
into the airways. RESULTS: A significant increase in eosinophil infiltration into
the airways was seen in sensitized and challenged animals compared with control
animals without sensitization. Among animals receiving antigenic exposure for
either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited
30 microg/kg histamine-induced increase in EB dye extravasation to a similar
degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance
(more than 90% inhibition in all groups). The minimal dose of procaterol to
inhibit 3 microg/kg histamine-induced microvascular leakage was not different
between nonsensitized control animals and those sensitized and challenged for 3
weeks at all airway levels. CONCLUSION: Inhaled beta2-adrenoceptor agonists may
be also potent in attenuating microvascular leakage even in the airways with
chronic allergic inflammation.
PMID- 9645603
TI - Regulation of Vbeta germline transcription in RAG-deficient mice by the
CD3epsilon-mediated signals: implication of Vbeta transcriptional regulation in
TCR beta allelic exclusion.
AB - During the thymic development of alphabeta lineage T cells, maturation of the CD4
CD8- double-negative (DN) cells into the CD4+ CD8+ double-positive cells is
accompanied by the induction of TCR beta allelic exclusion. Recent studies have
shown that these events are regulated by the signals through the pre-TCR complex
which consists of the TCR beta, pre-TCR alpha and CD3 components. The Vbeta
germline transcripts are detected prior to the TCR beta chain gene rearrangements
in the DN thymocytes. To examine the effects of the pre-TCR-mediated signals on
Vbeta germline transcription, we analyzed thymocytes from RAG-2-deficient mice
treated with anti-CD3epsilon antibody. The germline transcripts of all Vbeta we
examined, except for Vbeta14, were down-regulated by the anti-CD3epsilon antibody
treatment. These data indicate that the regulation of Vbeta germline
transcription by the signals through the pre-TCR complex may reflect the
modulation of Vbeta accessibility to the VDJ recombinase, which contributes to
TCR beta allelic exclusion.
PMID- 9645604
TI - Prolongation of allograft survival by administration of mAb specific for the
three subunits of IL-2 receptor.
AB - The IL-2 receptor (IL-2R) gamma chain, the so-called common gamma (gamma(c))
chain, which is shared with multiple cytokine receptors, plays important roles in
the immune system. Here we assessed the immunosuppressive ability of mAb specific
for the gamma(c) chain in induction of cytotoxic T lymphocytes (CTL) and
allograft rejection in combination with mAb specific for the alpha and beta
chains of IL-2R. CBA/N (H-2k) mice were injected i.p. with allogeneic splenocytes
from BALB/c (H-2d) mice, and then administered with combinations of anti-IL-2R
alpha, anti-IL-2R beta and anti-gamma(c) mAb or a control mAb. Addition of anti
gamma(c) mAb together with anti-IL-2R alpha and anti-IL-2R beta mAb induced a
complete inhibition of CTL response. The numbers and populations of CD4+ CD8- and
CD4- CD8+ T cells were not significantly affected by administration of the three
anti-IL-2R mAb, whereas NK cells were completely depleted in spleens of mice
treated with the anti-IL-2R mAb. Furthermore, skin allograft survival was also
significantly prolonged by administration of the three anti-IL-2R mAb. These
results suggest that the anti-gamma(c) mAb in combination with anti-IL-2R alpha
and anti-IL-2R beta mAb is capable of suppressing induction of CTL and NK cells,
resulting in prolongation of skin allograft survival.
PMID- 9645605
TI - In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated
sialyl compounds.
AB - There is accumulating evidence that sulfated lipids, sulfated oligosaccharides
and other sulfated compounds are reactive with selectins in a manner that
interferes with selectin interactions with their natural ligands. In the report
we describe the ability of sulfated lipids (sulfatides and gangliosides) and
multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig
to neutrophils. The in vivo ability of these compounds to block lung injury in
rats following i.v. infusion of purified cobra venom factor (CVF), which induces
injury that is L- and P-selectin dependent, was also determined as well as
effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There
was a significant correlation between the ability of sulfated lipids and sialyl
compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to
protect against P-selectin-dependent acute lung injury induced by CVF. The
biological effects of these sulfated compounds were also associated with
diminished accumulation of neutrophils. The protective effects of these compounds
may be linked to their ability to interfere with P-selectin binding to counter
receptors on neutrophils.
PMID- 9645606
TI - Requirement for p56(lck) tyrosine kinase activation in Th subset differentiation.
AB - The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented
with regard to its role in regulating T cell activation and thymocyte development
through delivery of signals via the mature alphabeta TCR as well as the pre-TCR.
Little is known, however, about the role of Lck in Th cell subset differentiation
in the periphery. Here, we assess the requirement for tyrosine kinase activation
of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck
(DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that
directs high expression in mature T cells, in which splenic CD4 T cells developed
normally. This Tg mouse provides a good experimental model system to investigate
the roles of Lck in mature T cell function in vivo. We show that the
catalytically inactive Lck protein at about twice-normal concentrations inhibits
Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of
the other T cell subset, Th1, intact. These data indicate a requirement for Lck
activity in Th2 cell differentiation, and a differential dependence for Lck
activity between Th2 and Th1 cell differentiation.
PMID- 9645607
TI - Dexamethasone enhances macrophage colony stimulating factor- and granulocyte
macrophage colony stimulating factor-stimulated proliferation of bone marrow
derived macrophages.
AB - Glucocorticoids are effective repressors of the immune system. We have examined
the effect of glucocorticoids on the proliferation of murine macrophages.
Dexamethasone by itself did not affect proliferation of differentiated or
undifferentiated bone marrow-derived macrophages (BMM) and elicited peritoneal
macrophages. However, dexamethasone enhanced the proliferation induced by
macrophage colony stimulating factor (M-CSF) of these cells. The effect of
dexamethasone was not restricted to M-CSF-dependent proliferation. Similarly,
dexamethasone enhanced granulocyte macrophage colony stimulating factor (GM-CSF)
dependent proliferation of BMM. In agreement, macrophages transfected with the
glucocorticoid receptor showed an enhancement of M-CSF-dependent proliferation.
The enhancement of proliferation by dexamethasone or the glucocorticoid receptor
was abolished by RU 486, an antagonist of the glucocorticoid receptor. Moreover,
the addition of antibodies against M-CSF inhibits the effect of dexamethasone,
suggesting that dexamethasone increases the autocrine production of M-CSF. This
only occurs when M-CSF or GM-CSF, which induce M-CSF, are present in the media.
In tissues, dexamethasone may enhance macrophage proliferation and contribute to
the resolution of the inflammatory states.
PMID- 9645608
TI - Regulation by transforming growth factor-beta1 of class II mRNA and protein
expression in fibroblast-like synoviocytes from patients with rheumatoid
arthritis.
AB - Transforming growth factor (TGF)-beta1 is an immunosuppressive cytokine that
modulates the expression of class II histocompatibility antigens on human cells.
Aberrant HLA class II expression on synovial lining cells of rheumatoid arthritis
synovial membrane has been described, and the extent and intensity of class II
expression on the cells was claimed to be linked with the severity of the
disease. In this study, the effects of TGF-beta1 on HLA class II antigen
expression in fibroblast-like synoviocytes (SFC) from rheumatoid synovectomy
tissues were determined by flow cytometric analysis and quantitative RT-PCR. We
found that pre-incubation of cells with TGF-beta1 was able to down-regulate IFN
gamma-induced DR protein expression in SFC. TGF-beta1, additionally, down
regulated IFN-gamma-stimulated class II transactivator (CIITA) and DRB mRNA
expression. The constitutive expression of CIITA mRNA was completely abolished
and the constitutive expression of DRB mRNA was decreased after treatment of SFC
with TGF-beta1 for 24 h. Addition of the TGF-beta inhibitor decorin to SFC for 24
h before TGF-beta1/IFN-gamma treatment was able to reduce the down-regulatory
effect of TGF-beta1 on DR antigen expression induced by IFN-gamma. Using
competitive RT-PCR, we found that SFC constitutively expressed decorin mRNA and
that treatment of cells with TGF-beta1 for 24 h reduced the constitutive
expression of decorin mRNA by 65%. Our results show that TGF-beta1 is able to
reduce the expression of HLA class II mRNA and protein, and suggest a tight
regulation between TGF-beta1 and decorin in SFC of the rheumatoid synovium.
PMID- 9645609
TI - Hsp72-mediated augmentation of MHC class I surface expression and endogenous
antigen presentation.
AB - Efficient recognition of tumor cells by cytolytic T lymphocytes (CTL) is often
dependent on the presentation of cytosolic peptides in the context of MHC class I
molecules. This process may be influenced by various molecular chaperones. To
analyze this influence, we have utilized B16 melanoma cells, which are not
effectively recognized by MHC class I-restricted CTL. This resistance to CTL is
apparently due to a very low level of surface MHC expression. We have found that
stably transfected clones of B16 which constitutively express the human heat
shock protein 72 (Hsp72) exhibit significantly increased levels of MHC class I
antigens on their surface. This Hsp72-mediated up-regulation of surface MHC class
I antigen represents an increase in the amount of functional MHC-peptide
complexes as measured by conformation-dependent antibodies and recognition by MHC
class I-restricted CTL. Expression of Hsp72 did not improve the antigen
presentation defect in cells lacking the activity of the transporter associated
with antigen presentation (TAP). Moreover, mice immunized with Hsp72-expressing
B16 cells, but not with control-transfected B16 cells, display significantly
increased resistance to a subsequent challenge with live, wild-type B16.
Together, our data demonstrate that the immune recognition of tumor cells can be
substantially enhanced by the suitable expression of a molecular chaperone.
PMID- 9645610
TI - Role of co-stimulation in CD8+ T cell activation.
AB - The two-signal model states that activation of naive T cells requires a signal 1
stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1
alone is sufficient for pre-activated T cells. Recently, however, it has been
shown that under certain conditions T cells can bypass the requirement for co
stimulation. For example, CD28-deficient mice, when immunized with lymphocytic
choriomeningitis virus, mount a vigorous cytotoxic T lymphocyte response and
clear the virus. As a continuous effort to unravel the mechanisms of T cell
activation, we previously reported activation of hybridoma T cells by recombinant
single-chain MHC molecules in the absence of antigen-presenting cells. In such
reconstitution experiments, since the signals delivered to the T cells are well
controlled, the contribution of any known or unknown signals can be ruled out. In
the present study, we analyzed the requirements for activation of naive T cells
by using splenocytes from TCR transgenic mice as a source of responding cells. We
observed that naive CD8+ T cells are fully activated by signal 1 alone, but that
co-stimulation lowers their activation threshold. Previously activated T cells
are fully responsive, even when the first stimulation was performed in the
absence of co-stimulation. They display a low activation threshold and are
insensitive to co-stimulation. The physiological relevance of this finding and
its consequences for immunotherapy as well as for our understanding of self
tolerance are discussed.
PMID- 9645611
TI - Multiple gene duplication and expression of mouse bcl-2-related genes, A1.
AB - Here we report the genomic cloning and characterization of the murine A1 genes,
which belong to the bcl-2 gene family. Southern analysis indicated the existence
of at least four A1 genes in the murine genome and four different A1 genes,
designated A1-a, -b, -c and -d, were cloned from the murine genomic library. The
A1-a, -b and -d genes consisted of two exons, whereas the A1-c gene contained 1
bp insertion in the coding region which may result in an aberrant and truncated
protein by frame-shift. With the exception of A1-c, the coding regions among A1
genes are highly conserved at >97% at the nucleotide level and at >96% at the
amino acid level. A1-a, -b and -d genes appeared to be expressed specifically in
organs containing many neutrophils. In neutrophils, A1-a, -b and -d transcripts
were detected at a comparable level. Our data suggest that the multiple A1 genes
in mice were generated by gene duplication and each of them may function as anti
apoptotic molecules in neutrophils.
PMID- 9645612
TI - A functional epitope on P-selectin that supports binding of P-selectin to P
selectin glycoprotein ligand-1 but not to sialyl Lewis X oligosaccharides.
AB - P-selectin mediates the adhesion of leukocytes to activated platelets and
endothelial cells. To characterize the functional domains of P-selectin for
ligand recognition, we established nine hybridoma cell lines secreting anti-rat P
selectin mAb. Among them, the mAb C215 bound both rat and human P-selectins, and
inhibited binding of rat and human P-selectins to P-selectin glycoprotein ligand
1 (PSGL-1) from HL-60 cells. In contrast, mAb C215 failed to inhibit the binding
of rat and human P-selectin-IgG to sialyl Lewis X (sLe(x)) oligosaccharides.
Epitope mapping of mAb C215 using synthetic decapeptides revealed that mAb C215
binds specifically to an eight-residue epitope that spans amino acids 76-83 of
rat P-selectin, a region completely conserved by human P-selectin. Synthetic
peptides containing the mAb C215 epitope inhibited binding of P-selectin to PSGL
1, but not to sLe(x) oligosaccharides, suggesting that the C215 epitope on P
selectin may directly interact with a particular site on the PSGL-1 core protein
essential for interaction with P-selectin, such as sulfated tyrosine residues.
Our results suggest the presence of two ligand recognition sites on P-selectin
necessary for binding to PSGL-1--one recognizes sLe(x), while the other
recognises the PSGL-1 core protein.
PMID- 9645613
TI - Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen:
adjuvant action is associated with enhanced regulatory cytokine production and
expression of the co-stimulatory molecules B7-1, B7-2 and CD28.
AB - Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis which
exerts a range of effects on the immune system, including the enhancement of IgE,
IgA and IgG production, delayed-type hypersensitivity reactions, and the
induction of experimental autoimmune diseases. However, the mechanism by which PT
mediates adjuvanticity remains to be defined. In this investigation we have shown
that PT can potentiate antigen-specific T cell proliferation and the secretion of
IFN-gamma, IL-2, IL-4 and IL-5 when injected with foreign antigens. A chemically
detoxified PT and a genetic mutant with substitutions/deletions in the S-1 and B
oligomer components that abrogate enzymatic and binding activity displayed no
adjuvant properties. In contrast, a non-toxic S-1 mutant devoid of enzymatic
activity but still capable of receptor binding retained its adjuvanticity,
augmenting the activation of both Th1 and Th2 subpopulations of T cells. In an
attempt to address the mechanism of T cell activation, we found that PT
stimulated the production of IFN-gamma and IL-2 by naive T cells and IL-1 by
macrophages. Therefore potentiation of distinct T cell subpopulations may have
resulted in part from the positive influence of IFN-gamma on the development of
Th1 cells and the co-stimulatory role of IL-1 for Th2 cells. Furthermore, PT
augmented expression of the co-stimulatory molecules B7-1 and B7-2 on macrophages
and B cells, and CD28 on T cells, suggesting that the adjuvant effect may also be
associated with facilitation of the second signal required for maximal T cell
activation. This study demonstrates that the immunopotentiating properties of PT
are largely independent of ADP-ribosyltransferase activity, but are dependent on
receptor binding activity and appear to involve enhanced activation of T cells.
PMID- 9645614
TI - The reactivity pattern of hemagglutinin-specific clonotypes from mice immunized
as neonates or adults with naked DNA.
AB - In contrast to adult mice immunized with influenza A virus strain WSN and plasmid
expressing WSN hemagglutinin (HA) gene which developed primary and secondary anti
HA antibody responses, mice immunized as neonates with virus failed to produce
anti-HA antibodies while those immunized with plasmid developed weak primary but
strong secondary responses. Analysis of the frequency of HA-specific B clonotypes
as well as their reactivity pattern (RP) showed that viral or genetic
immunization of adults increased the frequency of clonotypes which exhibit broad
RP. The most striking observation of our study is that immunization of neonates
with plasmid leads to increased synthesis of anti-HA antibodies as well as to an
increased frequency of clonotypes exhibiting an adult-like RP. In contrast,
neonatal immunization with virus caused a long-lasting unresponsiveness and the
few clonotypes stimulated in vitro exhibited only a monoreactive pattern. Isotype
patterns of mAb are also diversified in the case of mice immunized with plasmid
as neonates. Rapid replacement of neonatal with adult clonotypes may explain the
significant survival of the mice immunized with plasmid and challenged 1 or 3
months later with lethal doses of virus.
PMID- 9645615
TI - Predominant usage of the proximal poly(A) site in alpha mRNAs is not intrinsic to
the 3' termini.
AB - The maturation of IgM-expressing B cells to IgM-secreting plasma cells is
associated with both an increase in mu mRNA and the ratio of secreted to membrane
forms of mu mRNA. In contrast, previous studies demonstrated that in vitro the
secreted form of alpha mRNA (alpha s mRNA) predominates regardless of the stage
of B cell differentiation. The present study demonstrates that alpha s mRNA
predominates in both B cells derived from the germinal centers of murine Peyer's
patches and in the functional IgA memory population, suggesting that in vitro
events accurately represent the generation of a secretory IgA response in vivo.
Although the predominant usage of the alpha s poly(A) site is due to RNA
processing, it does not depend on either the alpha s poly(A) site, the 3' splice
site associated with the exon encoding the membrane exon of IgA (alphaM) or the
alphaM poly(A) sites. Analysis of the sequence of the intron between the alpha s
terminus and alphaM (alpha s-alphaM intron) demonstrates the existence of several
potential regulatory elements. Furthermore, the effects of deletions within the
alpha s-alphaM intron on 3' terminus usage demonstrate that the predominant usage
of the proximal terminus is not strictly dependent on the length of the intron.
Together with previous work, these observations support the idea that choice of
3' terminus for all Ig heavy chain genes is regulated by a similar mechanism, but
specific sequences within a heavy chain gene can impinge upon that mechanism.
PMID- 9645616
TI - Soluble human lymphocyte activation gene-3 modulates allospecific T cell
responses.
AB - Lymphocyte activation gene (LAG)-3, a member of the Ig superfamily, has been
characterized as an activation antigen of T cells and NK cells. LAG-3 has been
proposed as an alternate ligand for HLA class II due to some sequence homology
and similarities in exon-intron organization with CD4. Here, we report the
functional evaluation of a soluble Ig fusion molecule of human LAG-3 (LAG-3-Ig)
in T cell activation assays. Cytofluorimetry studies revealed LAG-3-Ig binding
predominantly to class II-expressing cells. In functional assays, inhibition of
primary allogeneic mixed lymphocyte response (MLR) and murine-human xenogeneic
MLR was observed in the presence of LAG-3-Ig. Effects of LAG-3-Ig addition were
not observed on mitogen-, recall antigen- or superantigen-mediated stimulation.
Cytotoxic T lymphocyte effector functions were also not affected by LAG-3-Ig.
Inhibition of alloresponses by LAG-3-Ig occurred within the first 24 h of
activation, resulting in a strong inhibition of IL-2 production. Unlike blockade
of the CD28 receptor, however, LAG-3-Ig-mediated inhibition could not be reversed
by exogenous IL-2 supplementation. Cytofluorimetric analysis of the phenotype of
cells exposed to LAG-3-Ig in MLR cultures revealed a decrease in IL-2 receptor
expression (CD25) on CD4+ cells in all donors tested. Based on the results from
these studies, we conclude that LAG-3-Ig inhibits alloresponses of naive
peripheral blood lymphocytes, by blocking the activation of a subpopulation of
allo reactive cells.
PMID- 9645617
TI - Regulation of in vitro and in vivo T cell activation by CD43.
AB - Accessory molecule interactions can be critical in determining the outcome of a T
cell's encounter with antigen. Cell adhesion proteins may augment T cell
responses by facilitating TCR engagement of the antigen-MHC complex, while co
stimulatory molecules may deliver distinct signals that modulate T cell
responsiveness. CD43 (leukosialin, sialophorin) has been suggested to influence
cell activation by steric hindrance based upon the large size and glycosylation
of the protein, as well as the relative abundance of the protein on the cell
surface. In this paper we examine both in vitro and in vivo T cell-dependent
responses in CD43-deficient mice. We demonstrate that T cells from CD43-deficient
mice are hyper-responsive following both in vivo and in vitro activation, and
that this is observed in response to not only TCR-CD3-mediated stimulation, but
also following receptor-independent activation. This data suggests that
mechanisms other than non-specific steric hindrance are important in the
regulation of T cell activation by CD43.
PMID- 9645618
TI - IL-6-deficient mice are resistant to the induction of experimental autoimmune
encephalomyelitis provoked by myelin oligodendrocyte glycoprotein.
AB - The role of IL-6 in experimental autoimmune encephalomyelitis (EAE) provoked by
myelin oligodendrocyte glycoprotein (MOG) was investigated using IL-6-deficient
mice. We show here that IL-6-deficient mice were resistant to the MOG-induced EAE
as compared to wild-type mice (one out of 18 versus 17 out of 20). The delayed
type hypersensitivity response, lymphocyte proliferation response and antibody
reactivity to MOG in IL-6-deficient mice were significantly lower than those in
wild-type mice. Furthermore, the histological examination revealed that no
infiltration of inflammatory cells was observed in the central nervous system of
IL-6-deficient mice. These results indicate that IL-6 may play a crucial role in
the induction phase of EAE. Given the potential relevance of this animal model
for multiple sclerosis (MS), it is possible that anti-IL-6 therapy may be useful
in the prevention of relapses of MS.
PMID- 9645619
TI - Surgical therapy for heart failure: care of the patient with partial left
ventriculectomy.
AB - Partial left ventriculectomy (PLV) surgery has gained significant attention
worldwide as a possible alternative to heart transplantation or as a therapy to
treat heart failure. This procedure offers an attractive choice to patients and
physicians because of the lack of need for immunosuppressive medications and a
decrease in the risk of rejection associated with transplantation. PLV surgery is
currently under investigation in several centers worldwide, but long-term
outcomes have yet to be definitively evaluated. The Cleveland Clinic Foundation
began performing PLV surgery in May 1996. Since that time, 57 patients have
received the procedure with actuarial survival of 82% at 1 year. The purpose of
this article is to highlight the clinical management of the postoperative PLV
patient.
PMID- 9645620
TI - Cardiac surgery and women.
AB - Coronary heart disease is just as serious a problem for women as it is for men,
yet historically women have been significantly underrepresented in research
studies related to the disease and treatment options, including cardiac surgery.
Cardiac surgery is a proven therapy for the management of coronary heart disease
in women. Research addressing the physical, psychosocial, and emotional issues
women face during the preoperative, postoperative, and recovery phases of surgery
is limited. Nurses play a pivotal role in the education and management of women
undergoing cardiac surgery and need to be aware of unique issues related to the
experience. This article reviews the literature pertaining to women's issues
during the perioperative and recovery phases of cardiac surgery.
PMID- 9645621
TI - The delirious cardiac surgical patient: theoretical aspects and principles of
management.
AB - Delirium, an etiologically nonspecific disorder of consciousness characterized by
prominent deficits in attention, cognition, and perception, affects more than one
third of adult cardiac surgical patients. Despite the frequency of occurrence and
the increased morbidity and mortality associated with it, the diagnosis is
commonly late or missed, and management is less than optimal. This article
addresses the recognition and management of delirium. Nurses who develop an index
of suspicion for the diagnosis and acquire the diagnostic and interventional
skills required to address this cerebral complication of cardiac surgery may well
decrease its incidence and severity.
PMID- 9645622
TI - Outcomes measurement.
AB - Patient outcomes have been referred to as the "ultimate definition of
effectiveness and efficiency," and there is an increasing emphasis on identifying
and measuring the results of interventions and practice. This new department will
focus on issues surrounding patient outcomes such as definitions, measurement,
sources of data, nurse-sensitive versus multidisciplinary outcomes, and
determining the evidence on which to base practice. The goal of the department is
to stimulate questions and encourage discussion that will contribute to the
necessary knowledge for defining, measuring, and ultimately improving
cardiovascular patient outcomes.
PMID- 9645623
TI - Factors influencing selected lengths of ICU stay for coronary artery bypass
patients.
AB - This study examines factors influencing the length of intensive care unit stay
for patients after coronary artery bypass surgery. Profiles of patients with
selected lengths of ICU stay were identified for Group 1 (< or =1 day) and Group
2 (> or =2 days). Medical records of 175 patients who had undergone this
procedure at an urban teaching hospital were reviewed. Patients who had a 1-day
ICU length of stay were younger (mean=62.39, SD=10.88) and had comorbidities such
as hypertension. Those patients with an ICU length of stay 2 days or longer were
older (mean=68.18, SD=11.84) and had preoperative comorbidities such as
congestive heart failure, chronic obstructive pulmonary disease, ejection
fraction <50%, and need for an intra-aortic balloon pump. Atrial dysrhythmias,
low cardiac output syndrome, renal insufficiency, and respiratory insufficiency
were the postoperative complications associated with a prolonged ICU length of
stay. Knowledge of the factors influencing selected lengths of ICU stay will
enable nurses to choose patients for critical pathways and to anticipate
postoperative problems in high-risk patients.
PMID- 9645624
TI - Patient perceived health status, hospital length of stay, and readmission after
coronary artery bypass surgery.
AB - This study evaluates the effect of length of stay and baseline health status on
health status and readmission rates 3 months after coronary artery bypass graft
surgery. Baseline health status showed a trend toward worse scores for patients
who were readmitted. Readmitted patients had longer lengths of stay, and worse 3
month health status scores, and women and patients with heart failure had higher
readmission rates. It may be possible to identify patients at risk for
readmission using clinical variables, length of stay, and health status. If a
predictive model can be developed, then interventions can be developed and tested
to decrease the rate of unplanned readmissions.
PMID- 9645625
TI - Patient education for discharge after coronary bypass surgery in the 1990s: are
patients adequately prepared?
AB - Short hospitalizations for patients undergoing coronary artery bypass grafting
(CABG) require continuous nursing evaluation of patients' discharge education.
Six institutions collaborated in surveying 300 postoperative patients with CABG
to identify learning priorities and patients' perceptions of the effectiveness of
discharge education. Data analysis from the self-administered questionnaire
demonstrated consistent patient priorities across institutions. Differences in
teaching methods and content did not affect perceived preparedness or importance
scores. Regional experience demonstrates that variable teaching efforts meet
patients' priorities and provide high overall patient preparedness for discharge.
Patients with the shortest hospitalizations had higher preparedness scores.
PMID- 9645626
TI - Complementary therapy and cardiac surgery.
AB - Mind-body techniques and complementary care may assist people who are undergoing
surgery and those recovering from cardiac surgery to cope with the event, the
process of recovery, and accompanying lifestyle changes. These approaches can
provide cardiac patients with nonpharmacologic tools that may prevent further
coronary artery disease and the development of dysrhythmias. The Complementary
Care Center at Columbia-Presbyterian Medical Center was developed to clinically
apply and research the use of nonallopathic, complementary modalities with
patients receiving care at the medical center, including those undergoing cardiac
surgery.
PMID- 9645627
TI - Cellular sequences in stealth viruses.
AB - Cloned DNA obtained from the culture of an African green monkey simian
cytomegalovirus-derived stealth virus contains multiple discrete regions of
significant sequence homology (p values ranging from 4 x 10(-3) to 1 x 10(-20))
to portions of known human cellular genes. The stealth virus was cultured from a
patient with chronic fatigue syndrome (CFS). Earlier studies had revealed
considerable sequence heterogeneity within DNA fragments isolated from virus
infected cells. A set of polymerase chain reaction (PCR) primers generated
different PCR products when tested on stealth virus cultures from 4 patients with
CFS. Several of the PCR products also contain regions of significant partial
homology to distinct cellular sequences, including sequences repetitively
expressed throughout the cellular genome. Stealth viruses may play an important
role in the origins and in the genetic diversity of both viral and cellular
sequences.
PMID- 9645628
TI - Fluorescent in situ hybridization detection of HER-2/neu gene amplification in
rhabdomyosarcoma.
AB - Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in
childhood, comprising 45-50% of childhood sarcomas. Cytogenetic studies of this
tumor are rare. In view of the paucity of cytogenetic data on this cancer and
based on the finding of HER-2/neu gene amplification in a number of cancers that
was detected mostly using the traditional technique of immunohistochemistry, we
decided to conduct a pilot study to investigate whether HER-2/neu gene
amplification in this tumor can be detected using the newer technique of
fluorescent in situ hybridization (FISH). Archival tissues of rhabdomyosarcoma
were retrieved and FISH using an HER-2/neu probe was undertaken on formalin-fixed
paraffin-embedded tissue sections using a protocol optimized for our laboratory
at Rhode Island Hospital. Out of 9 cases of rhabdomyosarcoma studied to date, 1
case clearly showed HER-2/neu gene amplification. Thus, FISH is a sensitive
technique suitable for the detection of oncogene amplification and the
delineation of tumor heterogeneity in this tumor. Future experiments utilizing
additional specimens from our centers as well as from other laboratories will be
needed to extend the finding in the present pilot study.
PMID- 9645629
TI - Chemokine expression in endothelial cells and monocytes is differentially
regulated.
AB - Endothelial cells play a critical role in the recruitment of immune cells due to
their position at the interface between circulating cells and the inflamed
tissue. In this study, human umbilical vein endothelial cells (HUVECs) and human
monocytes were used to investigate the role of various cytokines in the
regulation of C-C and C-X-C chemokine production. We have demonstrated that IL-4
and IL-10 negatively affect certain monocyte-derived chemokines, while not
suppressing HUVEC-derived chemokines. The differential induction of chemokines by
selected cytokines may help delineate the type(s) of leukocytes that are
recruited during certain phases of an inflammatory response.
PMID- 9645630
TI - Choline deficiency induces apoptosis and decreases the number of eosinophilic
preneoplastic foci in the liver of OXYS rats.
AB - Choline deficiency (CD) was previously shown to trigger apoptosis in rat
hepatocytes in culture and in vivo. In the present study we investigated the
effects of short-term withdrawal of choline from the diet on the expression of
putative preneoplastic foci in OXYS rats, an inbred strain with an inherited
overproduction of free radicals. Animals were fed a defined, choline-sufficient
(CS, control) or choline-deficient (CD) diet for 6 weeks. Eosinophilic,
glutathione S-transferase (pi class) (+) preneoplastic foci were found in
histologic sections of control OXYS rat liver. CD caused a 60% decrease in the
number of eosinophilic foci per liver section (27.0+/-6.1 vs. 10.6+/-4.6
foci/section) compared to CS controls. Apoptotic bodies were detected in 0.18+/
0.03% of hepatocytes in CD livers compared to 0.05+/-0.009% of hepatocytes in
controls. Cells which exhibited an apoptotic morphology in hematoxylin and eosin
stained sections were TUNEL-positive, confirming the induction of apoptosis. Also
in CD animals compared to controls, there was an increased expression of p27Kip1
protein, and a reduction in PCNA nuclear labeling and the number of mitotic
figures, consistent with an inhibition of cell proliferation in the livers of CD
animals. This study shows that the liver of OXYS rats with an inherited
overgeneration of free radicals retains sensitivity to CD, and that this p53
independent trigger of apoptosis can decrease the number of eosinophilic foci in
the livers of these animals.
PMID- 9645631
TI - Comparison of a pneumococcal common protein (PsaA) antibody ELISA and a PsaA
immune complex ELISA for detection of pneumococcal serum antibody.
AB - We examined and compared results from three assays, an enzyme-linked
immunosorbent assay (ELISA) and two immune complex ELISAs for analysis of the
serum antibody response to a native pneumococcal 37-kD common cell-wall protein
by using acute- and convalescent-phase sera from 56 patients with community
acquired pneumonia. The sensitivities of the ELISA, the undissociated and
dissociated immune complex assays were 85% (23 of 27), 78% (21 of 27) and 67% (18
of 27), respectively. To determine specificity, paired sera from patients with
pneumonia of other bacterial etiologies were tested. The specificities were 83,
83 and 72% for the ELISA, undissociated immune complex, and dissociated immune
complex, respectively. Based on this study, the sensitivities of the three assays
were not statistically different. These tests could be used retrospectively to
confirm invasive pneumococcal disease.
PMID- 9645632
TI - Epinephrine augments specific T-cell responses to antigen in C57BL/6 (H-2b) weak
responder mice by a CD8+ lymphocyte-dependent mechanism.
AB - Stress has been implicated as a factor in the pathogenesis of autoimmune
disorders. In order to determine the effect of adrenergic stress on immune
responses in vivo, C57BL/6 (B6; H-2b) mice, which respond weakly to hen-egg
lysozyme (HEL), were immunized on day 0 with HEL (50-200 microg s.q.) and
subsequently injected with epinephrine (EPI; 0.1-0.5 mg/kg s.q.) daily for up to
10 days. Controls included A/J mice (H-2k) which respond strongly to HEL. In some
experiments, B6 mice were depleted of CD4+ or CD8+ lymphocytes by monoclonal
antibody treatment in vivo, prior to immunization with HEL, and injection with
EPI. On day 10, single cell suspensions of draining lymph nodes (LN) and spleen
were examined for immune phenotype, proliferative responses to HEL, and
lymphokine production. Minimal specific proliferative responses were detected in
B6 mice compared to A/J mice. However, lymphocyte proliferation increased in HEL
immunized EPI-treated B6 mice but not in the A/J mice. IL-2-mediated
proliferation and IL-2 secretion were both increased in the HEL-immunized EPI
treated B6 mice. The depletion of CD8+ but not CD4+ lymphocytes in vivo abrogated
the effects of EPI, whereas adoptive transfer of naive CD8+ splenocytes to the
CD8-depleted mice restored specific responses in the HEL-immunized EPI-treated
animals. We conclude that EPI augments antigen-specific T-cell responses to HEL
in B6 mice by a CD8+ T-cell-dependent mechanism.
PMID- 9645633
TI - Comparison of alopecia areata in human and nonhuman mammalian species.
AB - Alopecia areata (AA) is a nonscarring form of inflammatory hair loss in humans.
AA-like hair loss has also been observed in other species. In recent years the
Dundee experimental bald rat and the C3H/HeJ mouse have been put forward as
models for human AA. AA in all species presents with a wide range of clinical
features from focal, locally extensive, diffuse hair loss, to near universal
alopecia. Histologically, all species have dystrophic anagen stage hair follicles
associated with a peri- and intrafollicular inflammatory cell infiltrate.
Autoantibodies directed against anagen stage hair follicle structures are a
consistent finding. Observations on AA pathogenesis suggest nonhuman species can
provide excellent models for the human disease. Ultimately, animal models will be
used to determine the genetic basis of AA, potential endogenous and/or
environmental trigger(s), mechanism(s) of disease initiation and progression, and
allow rapid evaluation of new and improved disease treatments.
PMID- 9645634
TI - Erythrasma treated with single-dose clarithromycin.
PMID- 9645635
TI - Topical metronidazole maintains remissions of rosacea.
AB - BACKGROUND: Rosacea is a chronic skin disease that requires long-term therapy.
Oral antibiotics and topical metronidazole successfully treat rosacea. Because
long-term use of systemic antibiotics carries risks for systemic complications
and adverse reactions, topical treatments are preferred. OBJECTIVE: To determine
if the use of topical metronidazole gel (Metrogel) could prevent relapse of
moderate to severe rosacea. DESIGN: A combination of oral tetracycline and
topical metronidazole gel was used to treat 113 subjects with rosacea (open
portion of the study). Successfully treated subjects (n = 88) entered a
randomized, double-blind, placebo-controlled study applying either 0.75% topical
metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo)
twice daily (blinded portion of the study). SETTING: Subjects were enrolled at 6
separate sites in large cities at sites associated with major medical centers.
SUBJECTS: One hundred thirteen subjects with at least 6 inflammatory papules and
pustules, moderate to severe facial erythema and telangiectasia entered the open
phase of the study. Eighty-eight subjects responded to treatment with systemic
tetracycline and topical metronidazole gel as measured by at least a 70%
reduction in the number of inflammatory lesions. These subjects were randomized
to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel.
INTERVENTIONS: Subjects were evaluated monthly for up to 6 months to determine
relapse rates. MAIN OUTCOME MEASURES: Inflammatory papules and pustules were
counted at each visit. Relapse was determined by the appearance of a clinically
significant increase in the number of papules and pustules. Prominence of
telangiectases and dryness (roughness and scaling) were also observed. RESULTS:
In the open phase, treatment with tetracycline and metronidazole gel eliminated
all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%)
displayed fewer papules and pustules after treatment, and 82 subjects (73%)
exhibited less erythema. In the randomized double-blind phase, the use of topical
metronidazole significantly prolonged the disease-free interval and minimized
recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43
subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39
subjects applying metronidazole gel (P<.05). The metronidazole group had fewer
papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema
also occurred less often in subjects treated with metronidazole (74% vs 55%).
CONCLUSION: In a majority of subjects studied, continued treatment with
metronidazole gel alone maintains remission of moderate to severe rosacea induced
by treatment with oral tetracycline and topical metronidazole gel.
PMID- 9645636
TI - Intra-incisional prophylactic antibiotics for dermatologic surgery.
AB - OBJECTIVE: To determine the efficacy of intra-incisional antibiotics in
decreasing the risk of wound infections in cutaneous surgery. DESIGN:
Prospective, blinded, randomized, placebo-controlled trial conducted during an 8
month period. SETTING: A private practice Mohs micrographic surgery referral
center. PATIENTS: Seven hundred ninety consecutive patients referred for Mohs
surgery or other dermatologic surgery were randomized to receive anesthesia
either with study compound or placebo. The 2 groups were equivalent with respect
to age and sex distribution and the lesions treated were similar in character. No
patients were withdrawn for adverse effects. INTERVENTIONS: Patients received
local anesthesia before surgery with either buffered lidocaine hydrochloride or a
solution consisting of nafcillin sodium in buffered lidocaine. MAIN OUTCOME
MEASURES: All surgical wounds were evaluated in a blinded fashion at the time of
suture removal (5-7 days) and scored according to a standardized assessment chart
based on erythema, edema, and the presence of purulent discharge. RESULTS: Seven
hundred ninety consecutive patients with 908 surgical wounds were enrolled in
this study. A total of 12 wound infections were recorded. Eleven (2.5%) of these
occurred in the control group, while only 1 (0.2%) occurred in the nafcillin
group. This difference was highly significant (P = .003). Observers were blinded
to patient groupings particularly for surgical wound scoring. CONCLUSIONS: This
study offers strong supporting data for the use of a single intra-incisional dose
of an antibiotic administered immediately before dermatologic surgery. The use of
nafcillin and buffered lidocaine solution is inexpensive, safe, convenient, and
effective.
PMID- 9645637
TI - Human herpesvirus 8 in Italian HIV-seronegative patients with Kaposi sarcoma.
AB - OBJECTIVE: To evaluate the prevalence of human herpesvirus 8 (HHV-8) DNA
detection in a large series of human immunodeficiency virus-seronegative patients
with and without Kaposi sarcoma (KS) from the central and southern regions of
Italy where classic KS is prevalent. DESIGN: Samples of lesional, peripheral
unaffected, and distant normal skin and peripheral blood mononuclear cells
(PBMCs) from 33 patients with KS and PBMCs from 42 control subjects were analyzed
using single and nested polymerase chain reaction techniques for the presence of
HHV-8 DNA. PATIENTS: A total of 33 patients with KS not related to acquired
immunodeficiency syndrome (26 patients with classic KS and 7 patients with
iatrogenic KS) were studied. Furthermore, 2 control groups were enrolled. The
first group consisted of 13 healthy volunteers, the second of 29 patients
affected by different dermatological diseases. RESULTS: Human herpesvirus 8
sequences were found in 100% of lesional and perilesional specimens, in 33% of
the distant normal skin samples, and in 69.6% of the PBMCs from patients with KS.
A possible correlation between HHV-8 DNA in PBMCs and the clinical stage of the
disease was observed. Moreover, the prevalence of viral DNA in PBMCs from the
total control group was 23.8%. No viral DNA was detected in tissue biopsy
specimens taken from the control group. CONCLUSIONS: Our data suggest that HHV-8
could be a widespread virus, at least in Mediterranean regions where KS is more
prevalent, such as southern and central Italy. As with other herpesviruses, it
may be present lifelong in latent form somewhere in the body and may contribute
to the pathogenesis of KS when other predisposing conditions are present.
PMID- 9645638
TI - Prevalence of human herpesvirus 8 infection measured by antibodies to a latent
nuclear antigen in patients with various dermatologic diseases.
AB - BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all epidemiological
forms of Kaposi sarcoma (KS). The role of HHV-8 in dermatologic diseases other
than KS is controversial. Some studies based on polymerase chain reaction
findings suggest an association between HHV-8 and epithelial tumors of the skin,
lymphoproliferative disorders, or pemphigus. OBJECTIVE: To assess the prevalence
of antibodies against a latent nuclear antigen of HHV-8 in patients with various
dermatologic diseases. DESIGN: An indirect immunofluorescence assay was used to
search for HHV-8 antibodies. SETTING: Ambulatory or hospitalized patients from a
university hospital associated with a research laboratory. PATIENTS: Eighty-three
patients with various non-KS dermatologic diseases and 16 patients with KS who
were seronegative for the human immunodeficiency virus. Controls were 100 healthy
subjects living in the same area. RESULTS: Antibodies to HHV-8 were found in 100%
(16/16) of the patients with KS and 3.6% (3/83) of the patients with non-KS
dermatologic diseases: 1 patient with pemphigus vulgaris, 1 with discoid lupus
erythematosus, and 1 with bullous pemphigoid. The prevalence of antibodies to HHV
8 in controls was 2% (2/100) and was not significantly different than the
prevalence in patients with dermatologic diseases other than KS (P =.28).
CONCLUSIONS: Our serologic study confirms the higher prevalence of HHV-8
antibodies in patients with KS and demonstrates that contrary to other human
herpesviruses, HHV-8 is not a ubiquitous virus in France. We could not determine
any causal association between HHV-8 and pemphigus or lymphoproliferative
disorders of the skin.
PMID- 9645639
TI - Immunoapheresis in paraneoplastic pemphigus.
AB - BACKGROUND: Paraneoplastic pemphigus was first described in 1990 in 5 patients
with extensive mucocutaneous erosions, a distinct set of autoantibodies, and
underlying neoplasia. Since then, patients described have been middle-aged, have
suffered from prognostically unfavorable malignant neoplasms, and have responded
poorly to immunosuppressive agents. OBSERVATION: A 16-year-old boy was examined
with extensive oral erosions, halitosis that interfered with his quality of life,
and rapid weight loss. The suspected clinical diagnosis of paraneoplastic
pemphigus was confirmed by histopathological, immunofluorescence, and biochemical
(eg, immunoblotting and immunoprecipitation) findings as well as by the
demonstration of an inflammatory myofibroblastic tumor of the left
retroclavicular region. Despite administration of corticosteroids, followed by
excision of the neoplasm, clinical symptoms improved only slightly, and
autoantibody titers decreased only marginally. We therefore initiated an
immunoapheresis regimen with the use of sheep anti-human-IgG bead-formed agarose
gel (Sepharose; Pharmacia Biotech Comp, Vienna, Austria), which led to the
disappearance of circulating autoantibodies and the patient's recovery.
CONCLUSION: Immunoapheresis may represent a novel therapeutic option for patients
with paraneoplastic pemphigus who show little improvement after curative
treatment of their neoplasms.
PMID- 9645640
TI - Congenital melanocytic nevi with placental infiltration by melanocytes: a benign
condition that mimics metastatic melanoma.
AB - BACKGROUND: Placental metastases from cutaneous malignant melanoma from both the
mother and the fetus have been reported. The finding of benign-appearing
melanocytes in the placenta in association with congenital melanocytic nevi (CMN)
is more exceptional, with only 6 reports in the literature. Clinically, the
finding of melanocytes in the placenta in this setting can be alarming and might
erroneously lead to the diagnosis of metastatic melanoma. OBSERVATIONS: Herein,
we describe 3 additional patients with CMN with placental infiltration by
melanocytes with a benign phenotype. In the results of immunoperoxidase stains,
the melanocytic cells were positive for S-100 protein and HMB-45 in the 2 lesions
available for study. Staining of placental vessels with Ulex europaeus agglutinin
I (Vector Laboratories, Burlingame, Calif) failed to show intravascular
melanocytes in the 1 lesion available for study. We report for the first time DNA
diploidy in 2 lesions available for study, which were analyzed by DNA image
cytometry. We describe the first patient with a relatively small, nongiant CMN.
CONCLUSIONS: We support the notion of the aberrant migration of melanocytes from
the neural crest during fetal development as the most likely explanation of this
phenomenon and note the similarity to the association of CMN and leptomeningeal
melanocytosis. However, the precise histogenesis of this process remains
uncertain. Most importantly, our data provide further evidence for the benign
nature of this condition. Awareness of this entity is of vital importance in
avoiding overdiagnosis of melanoma in this clinical setting.
PMID- 9645641
TI - Familial segregation of hemangiomas and vascular malformations as an autosomal
dominant trait.
AB - BACKGROUND: The pathogenesis of infantile hemangiomas is not yet understood.
Growth factors and hormonal and mechanical influences have been thought to affect
the focal abnormal growth of endothelial cells in these lesions. However, these
influences may represent secondary responses to an underlying primary molecular
event leading to the development of hemangiomas. OBSERVATIONS: We report the rare
familial occurrence of hemangiomas and/or vascular malformations in 6 kindreds,
suggesting autosomal dominant inheritance. In these families, multiple
generations (2-4) were affected by hemangiomas or vascular malformations. In
contrast to the generally accepted female-male ratio of 3:1 to 4:1 associated
with sporadic hemangiomas, the families with hemangiomas in our study
demonstrated a 2:1 ratio. Additionally, vascular malformations and hemangiomas
were present in different members of the same family. The vascular lesions
appeared to be transmitted in an autosomal dominant fashion with moderate to high
penetrance. CONCLUSIONS: We have identified 6 families demonstrating autosomal
dominant segregation of childhood hemangiomas. Additionally, family members with
vascular malformations were identified in these kindreds. Physicians caring for
children with hemangiomas and vascular malformations should include in their
medical histories inquiries about vascular lesions in other family members, even
when obvious lesions are not present in the parents. The identification of the
mutation(s) underlying vascular lesions will provide insight into the
pathogenesis of these familial hemangiomas and, potentially, common sporadic
hemangiomas. In addition, such research would shed light on the regulation of
angiogenic processes during development.
PMID- 9645642
TI - Interactive mechanisms for teaching dermatology to medical students.
AB - OBJECTIVES: To develop interactive teaching mechanisms for an "Introduction to
Dermatology" course for medical students and to compare the effectiveness and
impact of these mechanisms on learning. DESIGN: Survey and before-after trial.
SETTING: Medical school. PARTICIPANTS: Second-year medical students
(approximately 200 per year). MAIN OUTCOME MEASURES: The teaching mechanisms were
evaluated through responses to questionnaire-based course evaluations (survey).
The impact of the CD-ROM program was assessed by performance in Kodachrome slide
based multiple choice examinations (before-after trial). RESULTS: Overall the
course was highly rated and among its components, the live-patient sessions, the
CD-ROM program, and the poster exhibit were rated most effective. There was no
difference in the examination performance of students who took the course before
and after inclusion of the CD-ROM program. High-scoring students attended a
significantly greater number of lectures in comparison with low-scoring students.
CONCLUSIONS: The 3 teaching mechanisms judged by students to be most effective
were also the most visual and interactive, suggesting that these attributes are
critical to learning dermatology. On the other hand, addition of the CD-ROM
program failed to produce differential improvement in short-term cognitive
skills.
PMID- 9645643
TI - What do medical students need and what do they want?
PMID- 9645644
TI - Human herpesvirus 8 as the infectious cause of Kaposi sarcoma: evidence and
involvement of cofactors.
PMID- 9645645
TI - Evolving knowledge of hemangiomas and vascular malformations: beyond strawberries
and port wine.
PMID- 9645646
TI - Chronic unilateral leg inflammation in a young man.
PMID- 9645647
TI - Multiple chronic lesions with peripheral scale.
PMID- 9645648
TI - Hypopigmentation of the extremities.
PMID- 9645649
TI - Multiple asymptomatic papules in the popliteal fossa.
PMID- 9645650
TI - Human herpesvirus 8 DNA sequences in pemphigus: the role of the virus in
oncogenic and autoimmune manifestations.
PMID- 9645651
TI - Therapeutic options for superficial basal cell carcinoma: the role of radiation
therapy.
PMID- 9645652
TI - Conservative clinical diagnoses in seborrheic keratosis.
PMID- 9645653
TI - Further evidence that syringolymphoid hyperplasia with alopecia is a cutaneous T
cell lymphoma.
PMID- 9645654
TI - Hypopigmented common blue nevi.
PMID- 9645655
TI - Oral mucosa is frequently affected in patients with dermatitis herpetiformis.
PMID- 9645656
TI - Human herpesvirus 6 infection in patients with exanthema after allogeneic bone
marrow transplantation.
PMID- 9645657
TI - Clustered angiofibromas on the ear of a patient with neurofibromatosis type 2.
PMID- 9645658
TI - Public education on-line.
PMID- 9645659
TI - Gamma ray imaging systems.
PMID- 9645660
TI - On the discrepancy between epidemiologic studies in individuals of lung cancer
and residential radon and Cohen's ecologic regression.
AB - There is still substantial confusion in the radiation effects community about the
inherent limitations of ecologic analysis. As a result, inordinate attention has
been given to the discrepant results of Cohen, in which a negative estimate is
observed for the regression of county mortality rates for lung cancer on
estimated county radon levels. This paper demonstrates that Cohen's ecologic
analysis cannot produce valid inference on the exposure-response relationship for
individuals unless lung cancer risk factors (smoking, age, occupation, etc.) for
individuals are statistically uncorrelated with indoor radon level within
counties or unless risk effects for radon and other factors are additive. Both of
these assumptions are contradicted in the literature. Thus, contrary to common
assumption, when a linear no-threshold model is the true model for radon risk for
individuals, higher average radon concentration for a county does not necessarily
imply a higher lung cancer rate for the county. In addition, valid inference from
county-level ecologic analysis and the elimination of the ecologic bias cannot be
achieved with the addition of county-wide summary variables (including
"stratification" variables) to the regression equation. Using hypothetical data
for smoking and radon and assuming a true positive association for radon and lung
cancer for individuals, the analysis demonstrates that a negative county-level
ecologic regression can be induced when correlation coefficients for smoking and
radon within county are in the range -0.05 to 0.05. Since adverse effects for
radon at low exposures are supported by analysis of miner data (all data and data
restricted only to low cumulative exposures), a meta-analysis of indoor radon
studies, and molecular and cellular studies, and since ecologic regressions are
burdened by severe limitations, the negative results from Cohen's analysis are
most likely due to bias and should be rejected.
PMID- 9645661
TI - Residential 222Rn exposure and lung cancer: testing the linear no-threshold
theory with ecologic data.
AB - In most rigorous epidemiologic studies, such as case-control and cohort studies,
the basic unit of analysis is the individual. Each individual is classified in
terms of exposure and disease status. However, in ecologic epidemiologic studies,
the unit of analysis is some aggregate group of individuals. Summary measures of
exposure and disease frequency are obtained for each aggregate, and the analyses
focus on determining whether or not the aggregates with high levels of exposure
also display high disease rates. The ecologic study design has major limitations,
including ecologic confounding and cross level bias. Cohen has attempted to
circumvent these limitations by invoking the linear no-threshold theory of
radiation carcinogenesis to derive aggregate "exposures" from individual-level
associations. He asserts that, "while an ecologic study cannot determine whether
radon causes lung cancer, it can test the validity of a linear-no threshold
relationship between them." Cohen compares his testing of the linear no-threshold
relationship between radon exposure and lung cancer to the practice of estimating
the number of deaths from the person-rem collective dose, dividing the person-rem
by the number of individuals in the population to derive the individual average
dose, and then determining individual average risk by dividing the number of
deaths by the number of individuals in the population. We show that Cohen's
erroneous assumptions concerning occupancy rates and smoking effects result in
the use of the wrong model to test the linear no-threshold theory. Because of
these assumptions, the ecologic confounding and cross level bias associated with
Cohen's model invalidate his findings. Furthermore, when more recent Iowa county
lung cancer incidence rates are regressed on Cohen's mean radon levels, the
reported large negative associations between radon exposure and lung cancer are
no longer obtained.
PMID- 9645662
TI - Response to Lubin's proposed explanations of our discrepancy.
AB - Lubin's proposal that a correlation between radon and smoking among individuals
might explain the very large discrepancy between our data on U.S. counties and
the prediction of linear no-threshold theory of radiation induced cancer is
tested. It is shown that even correlations far beyond the limits of plausibility
cannot explain an appreciable part of our discrepancy. On the other hand, Lubin
is commended for proposing a definite potential explanation for our discrepancy
that can be quantitatively tested for applicability to our analysis, and further
such proposals are strongly invited. All other explanations of our discrepancy
and all other reasons for not accepting our conclusions that are proposed in the
Lubin paper are shown not to be applicable. The role of plausibility in
epidemiological studies is discussed and shown to be all-important.
PMID- 9645663
TI - Response to criticisms of Smith et al.
AB - The various criticisms of our test of the linear no-threshold theory of radiation
carcinogenesis in the paper by Smith et al. are considered and shown to be
invalid. It is shown that there is no significant difference between the BEIR IV
formula and the formula we use, that the uncertainties in effective average radon
exposures in U.S. counties due to the issues they raise are not very large and
that even if they were implausibly large, the results of our study would not be
much affected. I review the seven essentially independent methods we used to
estimate smoking prevalence, all of which give the same results but most of
which, including the most important, were ignored by Smith et al.; explaining our
results by uncertainties in smoking data would require correlations between radon
and smoking that are grossly implausible. Our use of measurements of radon,
smoking, and lung cancer rates from different time periods is justified, and it
is shown that if more recent lung cancer rates are used, the results are not
changed. Problems in comparing Iowa data with our study are discussed. It is
shown that many of their criticisms of our study are more applicable to the case
control and cohort studies that they endorse. Many of their conclusions are
presented without valid supporting evidence. A simple procedure is suggested that
can easily settle any questions about the validity of our study; with this
procedure, I offer to show that any other published ecological study might give
invalid results. The point here is that our study is very different from all
other published ecological studies.
PMID- 9645664
TI - 237Np: oxidation state in vivo and chelation by multidentate catecholate and
hydroxypyridinonate ligands.
AB - Chemically, 237Np(V) is as toxic as U(VI), and radiologically, about as toxic as
239Pu. Depending on redox conditions in vivo, 237Np exists as weakly complexing
Np(V) (NpO2+) or as Np(IV), which forms complexes as stable as those of Pu(IV).
Ten multidentate catecholate (CAM) and hydroxypyridinonate (HOPO) ligands with
great affinity for Pu(IV) were compared with CaNa3-DTPA for in vivo chelation of
237Np. Mice were injected intravenously with 237NpO2Cl: those in a kinetic study
were killed 1 to 2880 min; in ligand studies, fed mice were injected
intraperitoneally with a ligand 5, 60, or 1440 min after 237Np(V) (molar ratio
5.6 to 73), mice fasted for 16 h were gastrically intubated with a ligand 3 min
after 237Np(V) (molar ratio 5.6 to 274), and all were killed 24 h after ligand
administration; tissues and excreta were radioanalyzed. Rapid plasma clearance
and urinary excretion of 237Np(V) resemble U(VI); deposition and early retention
in skeleton and liver resemble Pu(IV). The x-ray absorption near edge structure
spectroscopy (XANES) spectra of femora of 237Np(V)-injected mice, compared with
spectra of Np(V) and Np(IV) from reference solids, showed predominantly Np(IV).
Significant in vivo 237Np chelation was obtained with all of the HOPO and CAM
ligands injected at molar ratio 22; the HOPO ligands reduced 237Np in skeleton,
liver, and other soft tissue, on average, to 72, 25, and 25% of control,
respectively, while CaNa3-DTPA was ineffective. Two HOPO ligands injected 60 min
after 237Np (molar ratio 5.6) significantly reduced body and liver 237Np, and
three HOPO ligands given orally (molar ratio > or = 73) significantly reduced
body and liver 237Np, compared with controls. Combined with earlier work, these
results indicate that: the dominant neptunium species circulating and excreted in
urine is Np(V), while that in bone and liver deposits is Np(IV); Np(V) must be
reduced to Np(IV) before it can be stably chelated; efficient decorporation of
neptunium requires multidentate ligands that form exceptionally stable
actinide(IV) chelates and facilitate Np(V) reduction.
PMID- 9645665
TI - Radiofrequency electromagnetic fields (300 Hz-300 GHz) summary of an advisory
report. Health Council of The Netherlands: Radiofrequency Radiation Committee.
AB - In a report prepared by an expert committee of the Health Council of the
Netherlands, health-based exposure limits for radiofrequency electromagnetic
fields in the frequency range 300 Hz-300 GHz are given. The present paper is a
summary of the recommendations in the report and of their rationales.
PMID- 9645666
TI - Tritium concentrations inside the homes of occupationally exposed workers:
dosimetric implications.
AB - The average tritiated water concentration in the indoor air of the occupationally
exposed worker's residence (55 Bq m(-3), range 53-59 Bq m(-3)) was higher than
the indoor air of control residences (0.7 Bq m(-3), range 0.4-0.8 Bq m(-3)). The
worker had an average concentration of tritium-in-urine of 30 kBq L(-1) from
chronic intakes of occupational levels of tritiated water. Higher residential
concentrations of tritiated water vapor were due to tritium transferred by the
worker. Urine samples from an adult co-occupant were collected and had tritiated
water concentrations between 89 and 345 Bq L(-1). These concentrations were
higher than for individuals (range, 6-32 Bq L(-1)) living in other residences
having similar outdoor and indoor concentrations of tritiated water in air. The
range of measured tritiated water in urine was in agreement with the prediction
of biokinetic models for tritium intakes as recommended by the International
Commission on Radiological Protection Publication 56. The tritiated water vapor
in the indoor air of the exposed worker's residence contributed about 96% of the
daily tritium intakes. The annual average tritium dose to the family member (7
microSv) was well below the International Commission on Radiological Protection
Publication 60 recommended annual dose limit (1 mSv) for members of the public.
We conclude that, for a few members of the public living near a heavy-water
research reactor facility, daily intakes of tritium will relate to tritiated
water dispersed by the exposed worker, as well as to tritium transported by the
atmosphere from the reactor site.
PMID- 9645667
TI - Comparative studies of indoor radon concentration levels in Jordan using CR-39
based bag and cup dosimeters.
AB - Indoor radon concentration levels have been measured in 9 major cities of Jordan
using CR(-3)9 detectors placed in punched polyethylene bags to measure both radon
and thoron, and in cups to measure radon only. The average value of indoor radon
and thoron concentration levels measured with bag dosimeters vary from 32 to 107
Bq m(-3) and the indoor radon concentration levels measured with cup dosimeters
vary from 27 to 88 Bq m(-3). The indoor radon concentration levels in Irbid and
Zaraka are comparable to the world average of 27 Bq m(-3). In Ajloun, Jerash,
Salt, Tafilah and Amman, the indoor radon levels are greater than the world
average by a factor of up to 2, and in Madaba and Karak these levels are greater
than the world average by a factor of more than 3. The large variation in the
measured radon levels may be attributed to the large variation in the 226Ra
activity in the soil of the region.
PMID- 9645668
TI - Estimation of environmental gamma background radiation levels in Pakistan.
AB - For the purpose of preparing an environmental gamma radiation map of Pakistan,
the geological materials exposed in the country were divided into eight different
classes. Using average 238U, 232Th, and 40K content of these materials, total
absorbed dose rate in these rocks was calculated. The dose rate in the
environment ranged from 1 nGy h(-1) to 97 nGy h(-1) with a mean value of 59 nGy
h(-1). These data are presented as a dose rate map of Pakistan. This map provides
a usable regional picture of environmental gamma background radiation levels
excluding cosmic radiation in Pakistan.
PMID- 9645669
TI - Model for estimating population impacts averted through the remediation of
contaminated soil.
AB - This is the second in a series of papers that discuss methodologies being
developed and employed by the U.S. Environmental Protection Agency in support of
its decisions on cleanup levels for radioactively contaminated sites that are to
be remediated and released for public use. It describes a model, CU-POP, designed
by the U.S. Environmental Protection Agency to obtain estimates of the potential
collective radiological health impacts over specific periods of time (100, 1,000
and 10,000 y following cleanup), both on and off site, due to residual
radioactive materials in on-site soil. Collective doses and risks are linear in
population density for the direct exposure, dust and indoor radon inhalation, and
soil ingestion pathways; it is assumed that specific fractions of all food grown
and all groundwater pumped at a site are consumed by on- and off-site
populations. The model was developed for application to a set of hypothetical
"reference" sites; its testing on a simple generic site is discussed briefly
here.
PMID- 9645670
TI - Effects of intake function shape on internal dose estimations.
AB - The estimated values of time-integrated dose equivalent are different if one
assumes continuous intake, such as is the case for longer-term environmental
exposures, instead of instantaneous intake, which is the assumption made for most
standardized computational procedures. This paper presents the solutions of the
first order kinetic equations for the ICRP 30 models of the respiratory system
(RS) and the gastrointestinal tract (GI) for continuous activity intake. These
solutions are applied to compute the cumulated number of disintegrations for
different intake and integration times in order to show the effects of the
assumptions of instantaneous intake vs. continuous intake on dose. For pulmonary
clearance class D compounds instantaneous and continuous intake functions result
in dose estimations agreeing to within 10% (when normalized to total intake) for
integration times larger than 8 d for both RS and GI, for the case of
radionuclides with radiological half-lives ranging between 8 d and 10(7) y. For
141Ce (class W) for both RS and GI the temporal intake function affects the dose
by less than 10% for integration times greater than 280 d. In this case, the
results for GI are less sensitive to the type of intake assumed than those for
RS: the ratio of the number of transformations with the two intake assumptions
has values of 0.8 or less for intake times of less than 7 d for GI and for intake
times of less than 153 d for RS. For radionuclides such as 89Sr and 90Sr (class
Y), the magnitude of the dose is very sensitive to the assumption made regarding
the intake and has a strong dependence on the radionuclide half-life: for a 10%
accuracy in dose evaluation for a continuous intake treated as instantaneous, the
integration time must be greater than 650 d for 89Sr and 18,000 d for 90Sr. For
all cases studied, the assumption of instantaneous intake overestimates the
integrated dose for a continuous intake. More accurate internal dose evaluations
may be made by consideration of the intake function shape when dose integration
times less than approximately 10 y are of interest and non-instantaneous intakes
are believed to have occurred.
PMID- 9645671
TI - Long-term decrease of atmospheric test 137Cs in the soil-prairie plant-milk
pathway in southern Chile.
AB - The time dependency of nuclear test 137Cs in soil, prairie plants, and milk was
observed on pastures of seven dairy farms in the 10th Region, Chile, from 1982 to
1997, without any appreciable deposition of radioactive fallout after 1983.
Whereas the 137Cs concentration in the soil decreased at a rate close to that of
the radionuclide's physical decay during the whole observation period, the rate
of decrease of the 137Cs concentration in the prairie plants and in the milk,
having been very rapid between 1982-1990, became slower between 1991-1997. The
effective half-lives of the concentration in plants were found to be 5.6 y and 12
y during the first and second observation periods, respectively. Similar half
lives of 5.5 y and 13 y were found for the concentration decline in milk during
each period. These data clearly demonstrate a reduction in the long-term decrease
of the 137Cs plant uptake, and consequently in the decrease of the 137Cs
concentration in milk, resulting from a decline of 137Cs availability for prairie
plants in the Hapludand soils over the whole 15-y observation period.
PMID- 9645672
TI - The domino effect.
PMID- 9645673
TI - Inhibitory actions of glucocorticoids on skeletal growth. Is local insulin-like
growth factor I to blame?
PMID- 9645674
TI - In situ hybridization of high density lipoprotein (scavenger, type 1) receptor
messenger ribonucleic acid (mRNA) during folliculogenesis and luteinization:
evidence for mRNA expression and induction by human chorionic gonadotropin
specifically in cell types that use cholesterol for steroidogenesis.
AB - The present studies were undertaken to examine the expression of the high density
lipoprotein (HDL) receptor, SR-B1 messenger RNA (mRNA) in ovarian cell types
during folliculogenesis and luteinization using in situ hybridization
histochemistry and to examine its hormonal regulation using Northern blots. For
the in situ study for HDL receptor mRNA localization, 21-day-old rats were
treated with 50 IU PMSG, and ovaries were collected 0, 24, and 56 h
postinjection. At 56 h, animals were treated with a single dose of hCG, and
ovaries were subsequently collected at 6-, 12-, 24-, and 72-h and 5-day
intervals. In addition, on day 4 of pseudopregnancy, a second dose of 50 IU hCG
or saline was administered, and ovaries were collected at 12, 24, and 48 h to
determine the induction of the expression of HDL receptor mRNA. The results of in
situ hybridization histochemistry showed that in the immature ovary, HDL receptor
mRNA is associated with theca interna and interstitial cells (stroma). The mRNA
expression in these cell types increased with PMSG treatment, but no signal was
detected in the granulosa cells. Northern blot analysis also showed a marked
increase in mRNA content in thecal and interstitial cells during follicular
development. During luteinization, the intensity of the signal began to appear in
the luteinized granulosa cells. With the completion of luteinization, the signal
in the corpus luteum tissue became more intense. Further treatment with hCG
increased the HDL receptor mRNA content compared with that in the saline-treated
control. These results demonstrate that the cholesterol-using cell types of the
ovary, namely the interstitial cells, thecal cells, and fully luteinized
granulosa cells are endowed with the HDL receptor mRNA, which provides credence
to the functional significance of the role of HDL receptor SR-B1 in cholesterol
transport and ovarian steroidogenesis.
PMID- 9645675
TI - Estradiol elevates protein kinase C catalytic activity in the preoptic area of
female rats.
AB - Estrogen acts in the brain to regulate female reproductive physiology and
behavior, and protein kinase C (PKC) is estrogen-regulated in many estrogen
responsive tissues. We examined whether estrogen regulates PKC in the
hypothalamus (HYP) and preoptic area (POA), brain regions which mediate
estrogenic control of female reproductive function. PKC activity in tissue from
hormone-treated and control female rats was measured, in the presence of phorbol
ester and calcium, by quantifying 32p incorporation into a substrate peptide. PKC
catalytic activity increased significantly in POA tissue extracts from estradiol
treated, ovariectomized (OVX) female rats but not in HYP or cortical extracts.
Phorbol ester potentiation of cAMP accumulation also was examined to determine
whether the ability of PKC to potentiate adenylyl cyclase activity was affected
by estrogen. PKC stimulation potentiated forskolin-induced cAMP accumulation to a
greater degree in POA, but not HYP, slices from estrogen-treated OVX female rats.
PKC enzyme levels were examined using phorbol-12,13-dibutyrate binding assays and
immunoblots. Estrogen treatment did not change phorbol ester binding affinity or
the density of binding sites in the POA or HYP. Immunoblots for the alpha, beta,
and gamma PKC isoforms combined, or the gamma PKC isoform alone, did not detect
differences between hormone-treated and control OVX female rats. Therefore,
estrogen treatment increased PKC catalytic activity in the POA of OVX female rats
but not in the HYP. However, the increased PKC catalytic activity was not
correlated with detectable changes in the level of the alpha, beta, or gamma PKC
isoforms or in the density of phorbol ester binding sites.
PMID- 9645676
TI - Obesity and insulin resistance in human growth hormone transgenic rats.
AB - A line of transgenic rats (heterozygotes) carrying a chimeric gene comprising a
regulatory portion of murine whey acidic protein and a structural portion of
human GH (hGH) genes developed severe obesity with age. To characterize
physiological mechanisms that lead to fat accumulation, an array of parameters
related to obesity were studied. Blood hGH levels were continuously low,
endogenous rat GH secretion was suppressed, and the pulsatility in peripheral GH
levels was absent. Plasma glucose, insulin, triglyceride, and FFA levels in the
male transgenic rats significantly exceeded those in nontransgenic littermates at
12 and 17 weeks, but not at 7 weeks, of age. All symptoms except hyperlipidemia
were restored to normal by treatment with an antidiabetic agent,
thiazolidinedione (troglitazone), for 1 week from 17 weeks of age. As phenotypic
expression of obesity was already evident before aberration of physiological
parameters, it was assumed that animals had a condition in which obesity or
hyperlipidemia caused hyperinsulinemia. Gene expression and enzymatic activity of
lipoprotein lipase in the adipose tissue in the transgenic rats were not
different from those in normal rats. In contrast, the gene expression level of
glycerol-3-phosphodehydrogenase was markedly elevated, suggesting that glycerol
synthesis was much enhanced in the adipocytes of the transgenic rats. In an i.p.
glucose tolerance test, the transgenic rats were not hyperglycemic at 7 weeks of
age; however, the animal became hyperglycemic at 15-17 weeks of age. Finally,
treatment with recombinant hGH for 1 week to produce pulsatile secretion reduced
the size of epididymal and kidney fat pads and restored normal weight gain. These
observations suggest that continuously low peripheral GH levels with the lack of
pulsatile secretion resulted in obesity and noninsulin-dependent diabetes
mellitus.
PMID- 9645677
TI - Physiological exposure to melatonin supersensitizes the cyclic adenosine 3',5'
monophosphate-dependent signal transduction cascade in Chinese hamster ovary
cells expressing the human mt1 melatonin receptor.
AB - Here, we report the effects of short exposure to melatonin on the human mt1 (h
mt1) melatonin receptor-mediated signaling in Chinese hamster ovary (CHO) cells,
and the consequences of an exposure that resembles the physiological pattern of
melatonin release on cAMP-mediated signal transduction. Short exposure (10 min)
of h mt1 melatonin receptors to melatonin (400 pM) inhibited forskolin-stimulated
cAMP formation, cAMP-dependent protein kinase activity, and phosphorylation of
the cAMP response element-binding protein. However, treatment of mt1-CHO cells
with melatonin in a manner that closely mimics the in vivo activation of
melatonin receptors (i.e. 400 pM melatonin for 8 h to mimic darkness) resulted in
a supersensitization of the cAMP-dependent signal transduction cascade during the
period of withdrawal (i.e. 16 h without melatonin to mimic the light cycle of a
diurnal photoperiod). During the period of withdrawal, forskolin induced a time
dependent (1-16 h) increase in cAMP formation (approximately 200% of control
cells). This effect of melatonin was dependent on the presence of the h mt1
melatonin receptor, as no potentiation of forskolin-induced cAMP formation was
observed in CHO cells transfected only with the neomycin resistance plasmid. The
time-dependent increase in forskolin-stimulated cAMP levels resulted in a
potentiation of cAMP-dependent protein kinase activity 1 h after withdrawal
(approximately 130% of control cells; P < 0.05) and in the number of cells
containing the phosphorylated form of cAMP response element-binding protein
(approximately 75% of cells at 1 and 16 h compared with 30% in control cells; P <
0.05). An increase in the undissociated state (G alphabetagamma) of Gi proteins
may underlie this phenomenon as demonstrated by the increase in pertussis toxin
catalyzed ADP-ribosylation of G proteins (217 +/- 48% of control; P < 0.05) after
melatonin withdrawal. This increase in the ribosylation was not due to an up
regulation of Galpha(i) protein, as no significant change in Galpha(i) protein
levels occurred at this time. We demonstrated that activation of the h mt1
melatonin receptor in a manner that resembles the physiological pattern of
melatonin exposure alters signaling, as potentiation of cAMP-mediated signal
transduction events is observed after hormone withdrawal. The CHO cells
expressing the human melatonin receptor may provide an in vitro cellular model in
which to investigate the putative signaling mechanisms leading to gene regulation
by melatonin.
PMID- 9645678
TI - The effect of cell-matrix interaction on parathyroid hormone (PTH) receptor
binding and PTH responsiveness in proximal renal tubular cells and osteoblast
like cells.
AB - The interaction of cells with the surrounding extracellular matrix (ECM) or
basement membrane (BM) brings about profound changes in cellular biological
responses, such as cell differentiation, proliferation, and gene expression. We
studied the effect of ECM on PTH receptor binding and on biological responses
mediated by PTH, in two cell preparations: 1) the proximal tubular OK opossum
kidney cell line; and 2) MC3T3-E1 cells, a clonal line of nontransformed murine
osteoblasts. Cells were plated on either plastic surfaces or on tissue culture
dishes coated with specific ECM components. In both cell types plated on collagen
type IV (Col-IV), PTH receptor binding, on day 4 of culture, was markedly
diminished, when compared with cells on plastic (approximately 45% inhibition, P
< 0.01). In addition, Col-IV dose dependently inhibited cAMP generation
stimulated by PTH (P < 0.001 vs. plastic), whereas cAMP generation by PGE2,
cholera toxin, and forskolin was not altered. In Northern blot analysis, a
PTH/PTH-related-protein receptor messenger RNA transcript was detected in both
the kidney and bone cells. However, only OK cells manifested a decreased
abundance of receptor messenger RNA when plated on Col-IV, compared with plastic.
The physiological significance of inhibited cAMP production by Col-IV was
evaluated by measuring the influence of different matrices on the activity of
Na+/H+ exchanger (NHE) in OK cells and cell mitogenic activity in MC3T3-E1 cells
(both responses are negatively modulated by cAMP). OK cells plated on Col-IV
showed 70% inhibition of NHE, compared with cells plated on plastic (P < 0.01).
PTH inhibits NHE activity in cells on plastic but stimulates exchanger activity
by 40% in cells plated on Col-IV. In MC3T3-E1 cells grown on plastic, PTH exerts
a dose-dependent antiproliferative effect, which is mediated by cAMP. This effect
is mitigated when cells are grown on Col-IV (40-50% less antiproliferative
effect). In summary, Col-IV, a maj or BM constituent, has a profound inhibitory
effect on PTH binding and PTH-mediated biological responses in both kidney
tubular cells and osteoblasts. Altered cellular function by Col-IV may be of
physiological relevance in states associated with altered composition of BM or
expansion of ECM (e.g. diabetes mellitus and interstitial fibrosis).
PMID- 9645679
TI - Expression of interferons-alpha and -gamma in testicular interstitial tissue and
spermatogonia of the rat.
AB - The testis is divided into two compartments: the seminiferous tubules and the
interstitial tissue. The latter essentially consists of the blood and lymphatic
vessels, testosterone-producing Leydig cells, and testicular macrophages. In the
exploration of the testicular antiviral defense system, we initially searched for
interferon (IFN) production by the seminiferous tubule cells. The site of virus
entry into the testis is probably the interstitial compartment; thus, it is
important to know whether and how the cells in this compartment are protected
against viral infection. In addition, as germ cell precursors (spermatogonia) are
only partially protected by the blood-testis barrier, it was important to explore
the antiviral capability of these cells. In this study we searched for IFN
production by Leydig cells, testicular macrophages, and spermatogonia after
exposure to Sendai virus. We also investigated the effect of viral exposure on
testosterone production by Leydig cells. Our results show that spermatogonia do
not constitutively express IFNs and give a very poor response to the virus. In
contrast, testicular macrophages constitutively produced type I IFNs, and this
production was markedly stimulated by Sendai virus. Leydig cells produced twice
as much type I IFNs as testicular macrophages after viral exposure, and they were
the only cells producing both IFNalpha and -gamma, with these IFNs being
dramatically induced/ increased in response to exposure to the virus.
Furthermore, incubation of Leydig cells with the Sendai virus stimulated
testosterone production. In conclusion, this study further establishes the
topography of IFN expression within the testis. This allows us to hypothesize
that the potential antiviral system represented by Leydig cells and, to a lesser
extent, by macrophages plays a key role in protecting both androgen production
and spermatogenesis.
PMID- 9645680
TI - The intracerebroventricular injection of interleukin-1beta blunts the
testosterone response to human chorionic gonadotropin: role of prostaglandin- and
adrenergic-dependent pathways.
AB - The present work extends our previous report that the intracerebroventricular
(i.c.v.) injection of interleukin-1beta(IL-1beta, 80 ng) significantly blunted
the testosterone response to 1 U/kg human CG (hCG), an effect that we attributed
to the stimulation of inhibitory pathways connecting the hypothalamus to the
testes. Systemic blockade of prostaglandin-dependent pathways with ibuprofen
(alpha-methyl-4-[2-methylpropyl]benzeneacetic acid; sodium salt), which did not,
in itself, alter the stimulatory effect of hCG on testosterone release in control
rats, modestly, but significantly (P < 0.05) reversed the inhibitory influence of
IL-1beta. In contrast, blockade of brain receptors for CRF was unable to alter
the effect of IL-1beta, as were lesions of the ventromedial hypothalamic nucleus,
a brain area implicated in the control of ovarian function. Blockade of beta
adrenergic receptors significantly prevented the decrease in testicular
responsiveness induced by the i.c.v. injection of IL-1beta. Finally, the central
injection of the beta-adrenergic agonist isoproterenol, as well as that of
norepinephrine, mimicked the ability of icv IL-1beta to blunt testicular
secretory activity and produced a marked (P < 0.01) decrease in the response to
hCG within 5 min of their administration. We propose that the explanation that
best fits our findings is that the i.c.v. injection of IL-1beta activates a
neural, catecholamine-dependent pathway that connects the brain and the testes
independently of the pituitary.
PMID- 9645681
TI - Inhibition of prostaglandin production by nimesulide is accompanied by changes in
expression of the cassette of uterine labor-related genes in pregnant sheep.
AB - The present study was designed to characterize effects of inhibiting PG
production by infusing nimesulide (CAS 51803-78-2) on PGE2 production and
expression of uterine labor-related genes in pregnant sheep. Myometrium,
endometrium, and placenta were collected following 6 h of i.v. nimesulide or
vehicle infusion. Infusions were commenced 9 h after onset of spontaneous term
labor. Tissues were also collected from term control ewes not in labor. PGE2 was
measured in fetal plasma by RIA. ER, OTR, Hsp 70 and 90, cPLA2, and PGHS-2
messenger RNA (mRNA) abundance in myometrium, endometrium, and PGHS-2 in placenta
were quantified by Northern blot analysis. Fetal plasma PGE2 decreased during
nimesulide infusion (P < 0.05). ER, OTR, Hsp 70, and Hsp 90 mRNA increased during
spontaneous term labor in vehicle infused ewes in both myometrium and
endometrium. In myometrium after nimesulide infusion, OTR and Hsp 70 mRNA
decreased significantly (P < 0.05) compared with vehicle infused animals, but the
decrease in Hsp 90 and ER mRNA fell outside the level of significance. In the
endometrium, nimesulide produced a decrease in ER and OTR mRNA (P < 0.05)
compared with vehicle infused animals, but the changes in Hsp 90 and 70 mRNA fell
outside the level of significance. Nimesulide reversed the up-regulation of PGHS
2 mRNA that occurred in myometrium, endometrium, and placenta during vehicle
infusion (P < 0.05). cPLA2 was only elevated in the endometrium in vehicle
infused ewes and did not change in either endometrium or myometrium after
nimesulide infusion. CONCLUSIONS: Inhibition of PG production resulted in
decreased fetal plasma PGE2. The decreased abundance of mRNA for several of the
well described cassette of utero-placental labor-related genes following
nimesulide inhibition may result from altered PG production.
PMID- 9645682
TI - Gonadotropin-releasing hormone pulses are required to maintain activation of
mitogen-activated protein kinase: role in stimulation of gonadotrope gene
expression.
AB - The present study examined the effect of alterations in GnRH signal pattern
(pulsatile vs. continuous; pulse frequency) on mitogen-activated protein kinase
(MAPK) activity and whether MAPK plays a role in regulating gonadotrope gene
expression. Pituitary MAPK activity was measured by immunoblot, using a phospho
specific MAPK antibody, corrected to the amount of total MAPK per sample. In vivo
studies were conducted in adult castrate testosterone-replaced male rats (to
suppress endogenous GnRH). Animals received pulsatile or continuous GnRH (or BSA
saline for controls) via jugular cannulas. Initial studies revealed that
pulsatile GnRH stimulated a dose-dependent rise in MAPK activity (30 ng, 2-fold
increase; 100 ng, 4-fold; 300 ng, 8-fold) 4 min after the pulse. The effect of
pulsatile vs. continuous GnRH was examined by administering 50-ng pulses (60-min
interval) or a continuous infusion (25 ng/min) for 1, 2, 4, or 8 h. Pulsatile
GnRH stimulated a 2- to 4-fold rise in MAPK activity (P < 0.05 vs. controls) that
was maintained over the 8-h duration. In contrast, continuous GnRH only increased
MAPK activity (2- to 3-fold; P < 0.05 vs. controls) for 2 h, with MAPK activity
returning to baseline at later time points. The effect of GnRH pulse frequency on
MAPK activation was determined by giving GnRH pulses (50 ng) at 30-, 60-, or 120
min intervals for 8 h. Maximal increases (3-fold vs. controls; P < 0.05) were
seen after 120-min pulses, with faster (30- to 60-min interval) pulses
stimulating 2-fold increases in MAPK activity (P < 0.05 vs. controls and 120-min
GnRH pulse group). The role of MAPK activation on gonadotrope (alpha, LHbeta,
FSHbeta, and GnRH receptor) gene expression was determined in vitro. Preliminary
studies demonstrated that the MAPK inhibitor, PD-098059 (50 microM), completely
blocked GnRH-induced increases in MAPK activity in adult male pituitary cells.
Further studies revealed that PD-098059 blocked gonadotrope messenger RNA (mRNA)
responses to pulsatile GnRH (100 pg/ml, 60-min interval, 24-h duration) in a
selective manner, with alpha, FSHbeta, and GnRH receptor (but not LHbeta) mRNA
responses being suppressed. These results show that a pulsatile GnRH signal is
required to maintain MAPK activation for durations of longer than 2 h, and that
slower frequency pulses are more effective. Further, MAPK plays a crucial role in
alpha, FSHbeta, and GnRH receptor mRNA responses to pulsatile GnRH. Thus,
divergent MAPK responses to alterations in GnRH signal pattern may be one
mechanism involved in differential regulation of gonadotrope gene expression.
PMID- 9645683
TI - Adrenal steroid regulation of neurotrophic factor expression in the rat
hippocampus.
AB - Adrenal steroids and neurotrophic factors are important modulators of neuronal
plasticity, function, and survival in the rat hippocampus. Adrenal steroids act
through two receptor subtypes, the glucocorticoid receptor (GR) and the
mineralocorticoid receptor, and activation of each receptor subtype has distinct
biochemical and physiological consequences. Adrenal steroids may exert their
effects on neuronal structure and function through the regulation of expression
of neurotrophic and growth-associated factors. We have examined adrenal steroid
regulation of the neurotrophins brain-derived neurotrophic factor, neurotrophin
3, and basic fibroblast growth factor, as well as the growth associated protein
GAP-43, through activation of GR or mineralocorticoid receptor with selective
agonists. Our findings indicated that in CA2 pyramidal cells, adrenalectomy
resulted in decreases in the levels of basic fibroblast growth factor and
neurotrophin-3 messenger RNA, which were prevented by activation of
mineralocorticoid but not glucocorticoid receptors. Adrenalectomy-induced
increases in GAP-43 and brain-derived neurotrophic factor messenger RNA levels
could be blocked by activation of glucocorticoid receptors in CA1, but not in
CA3, pyramidal cells. Thus the extent to which adrenal steroids regulate
hippocampal neurotrophic and growth-associated factors, appears to be dependent
both on the adrenal steroid receptor subtype activated and on the hippocampal
subregion examined.
PMID- 9645684
TI - Intestinal adaptation after extensive small bowel resection: differential changes
in growth and insulin-like growth factor system messenger ribonucleic acids in
jejunum and ileum.
AB - The distal small bowel exhibits greater adaptive growth than proximal segments
after partial small intestine resection. To explore this process, we evaluated
adaptive cellularity, intestinal insulin-like growth factor (IGF) system
messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in
jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno
ileal resection or intestinal transection and reanastomosis without resection,
followed by infusion of human recombinant IGF-I (2.4 mg/kgXday) or vehicle. After
7 days, resected rats demonstrated modest adaptive growth in jejunum and marked
cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum
(183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues.
IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly
increased ileal cellularity after resection, but had no effect in jejunum. IGF-I
markedly increased IGFBP-3 mRNA levels in jejunum after both transection and
resection. These data confirm that bowel resection induces greater adaptive
growth in ileum than jejunum. IGF-I administration modestly increases ileal, but
not jejunal, growth after resection. Increased levels of intestinal IGF-I and
IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel
adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited
jejunal vs. ileal growth after extensive jejuno-ileal resection.
PMID- 9645685
TI - Effects of aging and a high fat diet on body weight and glucose tolerance in
glucagon-like peptide-1 receptor -/- mice.
AB - Disruption of glucagon-like peptide-1 (GLP-1) receptor signaling in mice results
in mild glucose intolerance, principally due to elimination of the incretin
effect of GLP-1. Despite the inhibitory effects of GLP-1 on food intake, 6- to 8
week-old GLP-1 receptor -/-(GLP-1R-/-) mice were not obese and did not exhibit
disturbances of feeding behavior. As both diabetes and obesity frequently become
more phenotypically evident in older rodents, we studied the consequences of
aging and a high fat diet on glucose control and body weight in GLP-1R-/- mice.
No evidence of obesity or deterioration in glucose control was detected in 11-
and 16-month-old GLP-1R-/- mice (mean weight, 34.7 +/- 2.0, 30.5 +/- 1.5, and
34.6 +/- 2.8 g in male and 25.3 +/-1.6, 28.4 +/-1.2, and 31.9 +/- 2.9 g in female
GLP-1R+/+, GLP-1R+/-, and GLP-1R-/- mice, respectively; P = NS). After 18 weeks
of high fat feeding, GLP-1R-/- mice gained similar (males) or less (females)
weight than age- and sex-matched CD1 controls. No significant deterioration in
glucose tolerance was observed after high fat feeding in GLP-1R-/- mice. These
observations demonstrate that long term disruption of GLP-1 signaling in the
central nervous system and peripheral tissues of older mice is not associated
with the development of obesity or deterioration in glucose homeostasis.
PMID- 9645686
TI - Insulin induction of protein kinase C alpha expression is independent of insulin
receptor Tyr1162/1163 residues and involves mitogen-activated protein kinase
kinase 1 and sustained activation of nuclear p44MAPK.
AB - We examined the effect of insulin on protein kinase C alpha (PKCalpha) expression
and the implication of the mitogen-activated protein kinase kinase 1 mitogen
activated protein kinase (MAPK) pathway in this effect. PKCalpha expression was
measured by quantitative RT-PCR and Western blotting using Chinese hamster ovary
(CHO) cells overexpressing human insulin receptors of the wild type (CHO-R) or
insulin receptors mutated at Tyr1162/1163 autophosphorylation sites (CHO-Y2). In
CHO-R cells, insulin caused a time- and concentration-dependent increase in
PKCalpha messenger RNA, with a maximum at 6 h and 10-(8)M insulin. This increase
involved a transcriptional mechanism, as it was not due to stabilization of
PKCalpha messenger RNA and was associated with a similar increase in the
immunoreactive PKCalpha level. Insulin induction of PKCalpha expression involved
the MEK1MAPK pathway, as it was 1) almost completely suppressed by the potent
MEK1 inhibitor PD98059, 2) mimicked by the dominant-active MEK1 (S218D/S222D)
mutant, and 3) associated with sustained MAPK activation. In CHO-Y2 cells in
which the early phase of MAPK activation by insulin was lost and only the late
and sustained phase of activation was observed, insulin signaling of PKCalpha
expression was preserved and again involved the MEK1-MAPK pathway. Moreover, we
show that in both CHO-R and CHO-Y2 cells, insulin stimulation of PKCalpha gene
expression was associated with prolonged activation of nuclear p44MAPK. These
results indicate that induction of PKCalpha gene expression by insulin is
independent of Tyr1162/1163 autophosphorylation sites and correlates with
sustained activation of p44MAPK at the nuclear level.
PMID- 9645687
TI - Improvement of erectile function in diabetic rats by insulin: possible role of
the insulin-like growth factor system.
AB - Erectile dysfunction is commonly experienced in men with diabetes mellitus. We
report that the intracavernous pressure (ICP) rise in diabetic rats was 55% of
the control and returned to normal following insulin (I) or insulin plus free
oxygen scavenger (I + S) treatment. Insulin-like growth factor (IGF) binding
protein (IGFBP) -3, -4, and -5 messenger RNA (mRNA) levels in the major pelvic
ganglia (MPG) of diabetic rats were elevated by 2-fold, 2.6-fold, and 2.5-fold,
respectively. Both I and I + S returned IGFBP-4 and 5 mRNA levels to normal,
whereas IGFBP-3 gene expression was severely inhibited. IGFBP-2 gene expression
was greatly inhibited by diabetes and was unresponsive to treatment. In the penis
of diabetic rats, IGFBP-2 and -4 mRNA levels were low, whereas IGFBP-3 mRNA
levels were elevated 10-fold. These effects were reversed by I and I + S. I and I
+ S also corrected the IGFBP-3 expression pattern. IGF-I gene expression in the
penis and MPG was not significantly increased (P < 0.05) by diabetes and returned
to normal levels following I or I + S treatment. Because IGFs are potent
regulatory factors in vascular tone, this newly described activity of insulin may
play an important role in the improvement of erectile function seen clinically
and in animal models.
PMID- 9645688
TI - Antigen-presenting dendritic cells as regulators of the growth of thyrocytes: a
role of interleukin-1beta and interleukin-6.
AB - An accumulation of antigen-presenting dendritic cells (DC) in the thyroid gland,
followed by thyroid autoimmune reactivity, occurs in normal Wistar rats during
iodine deficiency, and spontaneously in diabetic-prone Biobreeding rats. This
intrathyroidal DC accumulation coincides with an enhanced growth rate and
metabolism of the thyrocytes, suggesting that both phenomena are related. Because
DC are known to regulate the hormone synthesis and growth in other endocrine
systems (i.e. the pituitary, the ovary, and the testis), we tested the hypothesis
that DC, known for their superb accessory cell function in T cell stimulation,
act as regulators of thyrocyte proliferation (and hormone secretion). We
investigated the effect of (Nycodenz density gradient) purified splenic DC from
Wistar rats on the growth rate of and thyroid hormone secretion by Wistar thyroid
follicles (collagenase dispersion) in culture. Various numbers of DC and
follicles were cocultured during 24 h. The proliferative capacity of thyrocytes
was measured by adding tritiated thymidine (3H-TdR) and bromodeoxyuridine, the
hormone secretion into the culture fluid was measured by using a conventional T3
RIA. Furthermore, antibodies directed against interleukin-1beta (IL-1beta), IL-6,
and tumor necrosis factor-alpha (TNF-alpha) were added to these cocultures to
determine the role of these cytokines in a possible DC regulation of thyrocyte
growth. Cocultures were also carried out in the presence of antimajor
histocompatibility complex-class I (MHC I), anti-MHC II, antiintercellular
adhesion molecule-1 (ICAM-1), and antilymphocyte function-associated antigen
1alpha (LFA-1alpha) antibodies to possibly interfere with DC-thyrocyte
interactions. The addition of DC to thyroid follicles clearly inhibited their 3H
TdR uptake, particularly at a 10:1 ratio, in comparison to follicle cultures
alone, both under basal conditions and after TSH stimulation (75 +/- 7% and 49 +/
11% reduction, respectively, n = 4). The follicle T3 secretion (after TSH
stimulation) was also suppressed by DC in this system, but to a lesser extent (at
best at an 1:1 ratio, 25 +/- 7% reduction, n = 4). The DC-induced inhibition of
thyroid follicle growth was totally abrogated after addition of anti-IL-1beta
antibodies; anti-IL-6 only had effect on the DC inhibition of non-TSH-stimulated
thyrocytes, whereas anti-TNF-alpha demonstrated no effect at all. The antibodies
to MHC and to adhesion molecules had also no effect on this DC-induced growth
inhibition. The effect of the different anti-cytokine and anti-adhesion
antibodies on the T3 secretion from thyroid follicles was not investigated. The
clear inhibition of thyrocyte growth by splenic DC (classical antigen-presenting
cells) again demonstrates the regulatory role of DC in endocrine systems.
Proinflammatory cytokines such as IL-1beta and IL-6 are important mediators in
this regulation. The here shown dual role of DC represents a link between the
immune and endocrine system, which may form the gateway to the understanding of
the initiation of thyroid autoimmune reactions and the thyroid autoimmune
phenomena seen in iodine deficiency.
PMID- 9645689
TI - Prostaglandin E2, interleukin 1alpha, and tumor necrosis factor-alpha increase
human osteoclast formation and bone resorption in vitro.
AB - Prostaglandin E2 (PGE2) and the cytokines interleukin (IL) 1alpha and tumor
necrosis factor (TNF)alpha increase bone resorption in vivo, but the effect of
these agents on osteoclastic bone resorption has never been studied in an in
vitro human system. Our recently described human bone marrow culture system, in
which osteoclasts are generated (vitronectin and calcitonin receptor-positive
cells which resorb bone), was used to study the effects of these agents. Addition
of indomethacin to macrophage colony-stimulating factor (M-CSF)-treated cultures
nearly abolished osteoclast parameters, indicating that prostaglandins are
virtually essential for human osteoclast formation. Additionally, PGE2 dose
responsively increased osteoclast numbers and bone resorption. The effects of M
CSF and PGE2 are independent, as demonstrated by unaltered PGE2 concentrations in
culture supernatants in spite of the dose-responsive increase in osteoclast
parameters in response to M-CSF. The generation of osteoclasts in the presence of
PGE2 occurred in favor of CD 14-positive macrophage formation. IL 1alpha and
TNFalpha increased osteoclast parameters in a dose-responsive manner. Maximum
stimulation yielded culture supernatant levels of PGE2 approximately the same as
those concentrations of exogenous PGE2 that dramatically induced osteoclast
formation. This osteoclast-inducing effect was inhibited both by indomethacin and
by the specific inhibitor of inducible prostaglandin G/H synthase, NS398, and
this was reversed by addition of exogenous PGE2. These results demonstrate
unequivocally that IL 1alpha and TNFalpha enhance human osteoclast formation and
suggest that they mediate their effects through PGE2.
PMID- 9645690
TI - Alpha, beta, and gamma mineralocorticoid receptor messenger ribonucleic acid
splice variants: differential expression and rapid regulation in the developing
hippocampus.
AB - Two different types of corticoid receptor molecules bind circulating
corticosterone in brain: mineralocorticoid receptors (MR) and glucocorticoid
receptors. MR exhibit the highest affinity for the endogenous glucocorticoid in
the rat, corticosterone. During development, low corticosterone levels influence
neurogenesis, and these effects are probably MR mediated. Three MR complementary
DNA clones, alpha, beta, and gamma, have been identified in the rodent. All of
these MR complementary DNA clones have identical coding regions, but differ
significantly at the 5'-untranslated end. Although the functional significance of
these three messenger RNA (mRNA) species remains unknown, one hypothesis is that
they reflect the ability of the brain to regulate the expression of MR, allowing
multiple factors to differentially control transcription in a tissue- and time
specific manner. To investigate this possibility, we examined the presence of
these distinct mRNA forms in the developing rat hippocampus (HC). In situ
hybridization with specific alpha, beta, and gamma complementary RNA probes was
performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We
found that there is differential expression of these forms in each of the HC
subfields from infancy to adulthood. y expression appears to be associated with
periods of cell birth and increased axonal sprouting. beta expression, on the
other hand, may be best linked to periods of synaptogenesis, growth of
commissural and associative terminal fields, and possibly active pruning. To
explore the possibility that the differential gene expression may be related to
corticosterone environment, adrenalectomy was performed. A rapid modulation of
the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These
findings suggest that the variation in expression and regulation during
development of the multiple MR transcripts could reflect a complex pattern of
developmental regulation that may involve a multitude of factors unique to each
postnatal age and to the different neuronal populations within the hippocampal
formation.
PMID- 9645691
TI - 5-Lipoxygenase metabolites inhibit bone formation in vitro.
AB - The leukotrienes and peptido-leukotrienes are 5-lipoxygenase (5-LO) metabolites
of arachidonic acid that appear to have unique effects on bone, distinct from
those of the prostaglandins. Application of exogenous leukotrienes in vitro and
in vivo results in increased osteoclast formation and bone resorption. While 5-LO
metabolites of arachidonic acid clearly stimulate osteoclastic bone resorption,
little is known concerning their effects on osteoblastic bone formation. We
examined the effects of the 5-LO metabolites 5-HETE, the leukotriene LTB4 and, as
representative of the peptido-leukotrienes, LTD4 on the formation of mineralized
nodules of fetal rat calvarial cells in the presence of dexamethasone and
recombinant human bone morphogenetic protein-2 (rhBMP-2). We also examined the
effects of these 5-LO metabolites on alkaline phosphatase activity and cell
proliferation in these cultures and the effects of 5-HETE and LTB4 on cultured
explants of neonatal murine calvariae. We found that the bone-forming capacity of
osteoblasts was impaired when cells were cultured in the presence of 5-LO
metabolites. These data indicate that metabolites of the 5-LO pathway are
negative regulators of bone formation. The continued presence of these
metabolites in the bone environment might account, in part, for the bone loss
associated with chronic inflammatory conditions.
PMID- 9645692
TI - The endothelin subtype A receptor undergoes agonist- and antagonist-mediated
internalization in the absence of signaling.
AB - The potent vasoconstrictor and mitogen to smooth muscle cells, endothelin-1 (ET
1), acts via two distinct G protein-coupled receptors, subtype A (ETAR) and
subtype B, that are coupled primarily to the Gq-phospholipase C signaling
pathway. It is known that ET-1 binding to ETAR promotes internalization, with
subsequent degradation of at least a portion of the bound ligand. To investigate
whether signaling is required for endocytosis, we developed stably transfected
lines of human embryonic kidney 293 cells expressing wild-type ETAR and a
receptor chimera (ETARC) in which the C-terminal cytoplasmic tail to ETAR was
replaced with that of the lutropin receptor, another G protein-coupled receptor,
but one which signals through the Gs-adenylyl cyclase pathway. ETARC binds ET-1
like ETAR, but is deficient in signaling. Using a combined concanavalin A/sucrose
gradient centrifugation technique to separate plasma membranes from other
cellular membranes, we found that [125I]ET-1 is rapidly internalized into ETAR
expressing cells at 37 C (t1/2 for internalization = 5 min; endocytic rate
constant = 0.1 min(-1); ETARC-expressing cells also internalize [125I]ET-1,
albeit at a somewhat slower rate than wild-type receptor (t1/2 for
internalization = 15 min; endocytic rate constant = 0.03 min(-1). Using
immunofluorescence confocal microscopy and an antibody developed to the N
terminal region of ETAR, qualitatively similar results were obtained. In
addition, it was found using confocal microscopy that the ETAR-selective
antagonist, BQ123, also promoted rapid internalization in cells expressing ETAR.
These results establish that inositol 1,4,5-trisphosphate signaling is not
required for ligand-mediated internalization of ETAR and suggest that a receptor
conformational change is necessary. Moreover, the finding that BQ123 promotes
ETAR internalization is novel and has potentially important implications in its
clinical use.
PMID- 9645693
TI - Sexual differentiation of aromatase activity in the rat brain: effects of
perinatal steroid exposure.
AB - Androgens regulate aromatase activity in the medial preoptic area and other
components of the brain circuit that mediates male sexual behavior. The levels of
aromatase activity within these brain regions are greater in males than in
females. As the activation of copulation requires aromatization of testosterone
to estradiol, this quantitative enzymatic difference between sexes could
contribute to the greater behavioral response displayed by males. The present
study was designed to test the hypothesis that gender differences in brain
aromatase activity of adult rats are dependent on the sexual differentiation of
the brain that occurs during perinatal exposure to gonadal hormones. Aromatase
activity was measured in vitro in microdissected brain samples using a sensitive
radiometric assay. We examined the effect of pre- and postnatal treatment with
testosterone propionate or diethylstilbestrol on basal levels and androgen
responsiveness of aromatase in adults. In addition, we examined what effect
prepubertal gonadectomy exerts on enzyme regulation. Our results demonstrate that
perinatal treatments with gonadal hormones that are known to differentiate sexual
behavior can completely masculinize the capacity for aromatization in the adult
female. The process that differentiates aromatase expression appears to depend on
androgen exposure and, in part, local estrogen synthesis, as diethylstilbestrol
was able to substitute for testosterone propionate. We also observed that
prepubertal gonadectomy reduced the levels of aromatase activity measured in
adult brain, suggesting that gonadal hormones that are secreted during puberty
may enhance the expression of aromatase activity in adulthood. From this study,
we conclude that testosterone and/or its estrogenic metabolites act on the
developing brain to determine the gender-specific capacity for aromatization and
to regulate androgen responsiveness within components of the neural circuitry
that mediates male sexual behavior.
PMID- 9645694
TI - Bidirectional transcription regulation of glial fibrillary acidic protein by
estradiol in vivo and in vitro.
AB - Glial fibrillary acidic protein (GFAP) expression shows cyclic variation in the
rat hypothalamus and hippocampus during the normal estrous cycle. To elucidate
the role of transcription in the regulation of GFAP, we examined levels of GFAP
intron 1 by in situ hybridization in the hypothalamus and hippocampus of normal,
cycling rats. On the afternoon of proestrus, when plasma estradiol levels are
highest, GFAP transcription and messenger RNA were both increased in the arcuate
nucleus of the hypothalamus and decreased in the outer molecular layer of the
dentate gyrus. In the hilus of the hippocampus, neither GFAP transcription nor
messenger RNA changed during the estrous cycle. In vitro, astrocytes showed
bidirectional responses, such that estradiol treatment increased GFAP
transcription in monotypic astrocytic cultures but decreased GFAP transcription
in astrocytes cocultured with neurons. The functionality of an estrogen response
element in the 5'-upstream region of the GFAP promoter was established by site
directed mutagenesis and binding of human recombinant estrogen receptor in gel
shift assays. We conclude that estrogen may act directly upon astrocytes by
estrogen receptor binding, and that the direction of the transcriptional response
is influenced by astrocyte-neuron interactions.
PMID- 9645695
TI - Hypothalamo-pituitary disconnection of the late-gestation ovine fetus results in
profound changes in cortisol secretion that are not reflected in commensurate
changes in adrenocorticotropin secretion.
AB - A prepartum increase in fetal glucocorticoid concentrations is essential for the
perinatal transition to extrauterine life for many mammalian species. In the case
of the sheep, this increase in cortisol is also the trigger for parturition, and
depends upon an intact hypothalamo-pituitary unit. Fetal sheep that have
undergone hypothalamo-pituitary disconnection (HPD) fail to have a prepartum
cortisol surge or initiate labor, despite apparently normal fetal ACTH
concentrations in late gestation. We have investigated whether a defect exists in
the regulation of pulsatile neurohormone secretion in the pituitaryadrenal axis
of the HPD sheep fetus, by comparing immunoreactive (ir) ACTH and cortisol
secretory dynamics in intact and HPD fetuses at 126 and 145 days of gestation
(normal gestation length, 147 days). The fetal surgery was conducted at 115 days
of gestation. Blood samples were collected at 5-min intervals for 2 h on each
experimental day, and the resulting irACTH and cortisol concentrations were
analyzed by multiple-parameter deconvolution and cross-correlation analysis.
Basal irACTH secretion was less (P < 0.01) in HPD fetuses than intact fetuses at
126 days, but it had recovered by 145 days. There were no differences in irACTH
half-life or the number or duration of irACTH secretory bursts between the two
groups of fetuses or the two gestational ages (GAs). The size of the irACTH
secretory bursts was not affected by the operation, but it increased with GA to a
similar extent in both groups of fetuses (P < 0.01). In keeping with the
observations for irACTH secretion, there was no effect of age or the operation on
cortisol half-life or on the number or duration of cortisol secretory bursts. In
contrast, there were dramatic age-related increases (P < 0.01) in the basal
cortisol secretion rate and the size of the cortisol secretory bursts in the
intact, but not the HPD, fetuses. Cross-correlation analysis revealed a
significant (P < 0.01) concordance between irACTH and cortisol secretion in only
the intact fetuses at 126 days; this was not apparent in the intact fetuses at
145 days, or in the young or old HPD fetuses. These findings confirm a major
defect in cortisol secretion in the late-gestation HPD fetus but suggest that
this is not caused by defects in irACTH secretion. Together with other
observations, these data suggest that ACTH may not be the sole, or primary,
regulator of adrenal cortisol secretion in the late-gestation ovine fetus.
PMID- 9645696
TI - Glucocorticoids increase vasopressin V1b receptor coupling to phospholipase C.
AB - Vasopressin (VP) stimulates pituitary ACTH secretion after binding to V1b VP
receptors (V1b-R) coupled to phospholipase C (PLC). This effect of VP on ACTH
secretion, unlike that of CRH, is resistant to glucocorticoid feedback. To
determine whether changes in V1b-R expression or signaling mediate the
refractoriness to glucocorticoids, the effects of glucocorticoids on pituitary VP
binding, V1b-R messenger RNA (mRNA) and VP-stimulated inositol phosphate (IP)
formation were studied in vivo and in vitro in the rat. Dexamethasone injection
for 7 days decreased VP binding but increased V1b-R mRNA, indicating that mRNA
levels do not reflect receptor number. In spite of the binding loss, VP
stimulated IP formation was enhanced in dexamethasone-treated rats, suggesting
that glucocorticoids increase the coupling efficiency of the V1b receptor to
phospholipase C. Pretreatment of pituitary cells in vitro with dexamethasone or
corticosterone, also potentiated IP formation by low and high doses of VP,
indicating that glucocorticoids act directly in the pituitary and not through
changes in hypothalamic factors. The effect is mediated by glucocorticoid
receptors because it was blocked by glucocorticoid but not mineralocorticoid
antagonists. Dexamethasone potentiated the stimulation of IP by other PLC
dependent ligands (GnRH, TRH) but not that by the calcium ionophore, ionomycin,
suggesting a site of action between the receptor and PLC. After treatment with
dexamethasone, in vivo or in vitro, Western blot analysis revealed marked
increases in the GTP binding protein, Galpha(q), which may account for the
potentiating effect of glucocorticoid on ligand-stimulated IP. The data
demonstrate that glucocorticoids increase coupling of the V1b-R with PLC thereby
providing a mechanism by which VP facilitates corticotroph responsiveness in
spite of elevated levels of plasma glucocorticoids during stress.
PMID- 9645697
TI - Unmasking of a periodic Na+ entry into glucose-stimulated pancreatic beta-cells
after partial inhibition of the Na/K pump.
AB - The cytoplasmic concentration of Na+ ([Na+]i) was measured in individual mouse
beta-cells using dual wavelength microfluorometry and the indicator sodium
binding benzofuran isophtalate. Under conditions known to induce large amplitude
oscillations in cytoplasmic Ca2+ (1.3 mM Ca2+; 11 mM glucose), [Na+]i remained
low and stable at 10-14 mM. Partial suppression of the Na/K pump with 50 microM
ouabain resulted in oscillations of [Na+]i in 65% of the cells (frequency, 0.13+/
O.O1 min(-l); amplitude, 4.4 +/-0.3 mM). The oscillations were unaffected by the
presence of 3 microM tetrodotoxin, but disappeared when the medium was depleted
of Ca2+ or supplemented with 10 microM methoxyverapamil. The analysis of the
ouabain effect was facilitated by replacing extracellular Ca2+ with 5 mM Sr2+. In
the Sr2+-containing medium, oscillations of [Na+]i were seen in more than 70% of
the beta-cells exposed to 11 mM glucose. Ouabain (50 microM) modified the [Na+]i
oscillations by increasing their amplitudes almost 3-fold and reducing the
frequency from once every 3 min to once every 10 min. A relationship between
oscillations of cytoplasmic Sr2+ and Na+ was apparent both from observations of
similar frequencies and for the modifications obtained with ouabain. It is
concluded that the glucose-induced oscillations of cytoplasmic Ca2+ result in a
rhythmic entry of Na+, usually balanced by the Na/K pump. A resulting periodic
consumption of ATP in the Na/K pump might have implications for the release of
insulin by affecting ATP-dependent processes associated with the plasma membrane.
PMID- 9645698
TI - Nerve growth factor processing and trafficking events following TrkA-mediated
endocytosis.
AB - We expressed the high affinity nerve growth factor receptor TrkA in Chinese
hamster ovary (CHO) fibroblasts to study nerve growth factor (NGF) trafficking
and processing events following receptor-mediated ligand internalization in a
nonneuronal and p75 minus cell line. These stable clonal cell lines express
approximately 2.5 x 10(5) TrkA receptors and bind 125I-NGF with high affinity (Kd
= 4 x 10(-10) M). The TrkA receptors are autophosphorylated on tyrosine residues
upon NGF stimulation and are capable of tyrosine phosphorylating downstream
signaling molecules. The t1/2 of 125I-NGF internalization is 5 min, and the
probability of an occupied TrkA receptor internalizing within 1 min at 37 C is
9.8%. By 2 h following endocytosis, less than 10% of internalized 125I-NGF is
degraded, as determined by TCA precipitation. Thirty minutes following ligand
endocytosis, endocytosed 125I-NGF is delivered back to the cell surface and
released by the cell (retroendocytosis), possibly by remaining associated with
recycling TrkA receptors. We measured the effect of acidification on 125I-NGF
TrkA association and found that, at pH 6, 40% of 125I-NGF remains bound. Thus,
NGF may remain associated with the TrkA receptor at low pH conditions in the
endosome and can thereby be targeted back to the plasma membrane for release by
the cell. IN CONCLUSION: 1) TrkA, in the absence of p75, is fully capable of
mediating 125I-NGF endocytosis; 2) internalized 125I-NGF is slowly and
inefficiently degraded; 3) following internalization, 125I-NGF is
retroendocytosed; and 4) the ability of 125I-NGF to remain receptor-associated
during acidic conditions may provide a mechanism for its retroendocytosis via
recycling TrkA vesicles.
PMID- 9645699
TI - Phospholipase D- and protein kinase C isoenzyme-dependent signal transduction
pathways activated by the calcitonin receptor.
AB - The calcitonin receptor expressed by the porcine LLC-PK1 renal tubule cells is a
seven-transmembrane domain, G protein-coupled receptor activating adenylyl
cyclase and phospholipase C. Salmon calcitonin stimulated dose- and time
dependent release of the phospholipase D-dependent phosphatidylcholine product
[3H] choline with an EC50 = 2.5 +/-0.3 x 10(-8) M, similar to that determined for
phosphoinositide metabolism (EC50 = 4.5 +/-1.0 x 10(-8)M). The hormone failed to
induce release of [3H]phosphocholine and [3H]glycerophosphocholine, ruling out
activation of phosphatydilcholine-specific phospholipase C and phospholipase A.
Calcitonin stimulated phosphatidic acid, a product of phospholipase D-dependent
phosphatydilcholine hydrolysis. Activation of phospholipase D was confirmed by
release of [3H]phosphatydilethanol, a specific and stable product in the presence
of a primary alcohol. Activation of calcitonin receptor induced diacylglycerol
formation, with a rapid peak followed by a prolonged increase, due to activation
of phospholipase C and of phospholipase D. Consequently, the protein kinase-C
alpha, but not the delta isoenzyme, was cytosol-to-membrane translocated by
approximately 50% after 20 min exposure to calcitonin, whereas protein kinase-C
zeta, which was approximately 40% membrane-linked in unstimulated cells,
translocated by approximately 19%. The human calcitonin receptor expressed by BIN
67 ovary tumor cells, although displaying higher affinity for calcitonin, failed
to activate phospholipase D and protein kinase-C in response to the hormone. This
receptor lacks the G protein binding consensus site due to the presence of a 48
bp cassette encoding for a 16-amino acid insert in the predicted first
intracellular loop. This modification is likely to prevent the calcitonin
receptor from associating to phospholipase-coupled signaling.
PMID- 9645700
TI - Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores
insulin sensitivity: independent effect from secondary weight reduction in
genetically obese Zucker fatty rats.
AB - Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant
circulating adrenal steroids in humans. Administration of DHEA has been reported
to have beneficial effects on obesity, hyperlipidemia, diabetes, and
atherosclerosis in obese rodents, although its effects on insulin resistance have
not been fully elucidated. In this study, the effects of DHEA treatment on
insulin sensitivity were investigated in genetically obese Zucker rats, an animal
model of insulin resistance, using the euglycemic clamp technique. After 0.4%
DHEA was administered for 10 days to female obese Zucker rats aged 16 weeks, body
weight and plasma insulin decreased and glucose disposal rate (GDR), which was
normally reduced in obese rats, rose significantly compared with age- and sex
matched control obese rats. On the other hand, although the pair-fed obese rats
also showed levels of weight reduction similar to those of DHEA-treated rats, the
increase in GDR of DHEA-treated rats was significantly greater than in pair-fed
rats, suggesting a direct ameliorating effect of DHEA on insulin sensitivity of
obese rats. Serum concentration of tumor necrosis factor (TNF)-alpha, one of
cytokines causing insulin resistance, was also reduced significantly in DHEA
treated, but not in pair-fed obese rats. In conclusion, our results suggest that
DHEA treatment reduces body weight and serum TNF-alpha independently, and that
both may ameliorate insulin resistance in obese Zucker fatty rats.
PMID- 9645701
TI - Spontaneous expression of inducible nitric oxide synthase in the hypothalamus and
other brain regions of aging rats.
AB - Our laboratory has demonstrated that aging in Brown-Norway rats is associated
with decreased LH pulse amplitude and reduced GnRH and LH responsiveness to
excitatory amino acids (EAA), presumably through the NMDA receptor (NMDAR).
Nitric oxide (NO) is a neurotransmitter postulated to be involved in hypothalamic
synaptic events required for normal GnRH regulation through the activation of
neuronal nitric oxide synthase (nNOS). Paradoxically, excessive stimulation of
nNOS by NMDAR or the expression of inducible nitric oxide synthase (iNOS) can
lead to supraphysiological levels of NO acting as effector of apoptosis with
resultant decreased regional neuronal function. The aims of this study were to
determine: 1) whether aging in the preoptic area/medial basal hypothalamus is
associated with altered NO synthesis; 2) the possible roles of the NMDAR/nNOS
cascade and iNOS in this process; and 3) whether alterations in the levels of NOS
isoforms are specific to this region of the brain. Brown Norway male rats (N = 5)
at ages 1 (immature), 3 (adult), and 24 (old) months, were used for measuring
NMDARs in hypothalamic membranes by the binding of a (3H)-NMDAR ligand. Another
series of the same age groups of rats (N = 9) were used to determine by Western
blot the contents of NMDAR, nNOS, and iNOS in the hypothalamus, and only iNOS in
the frontal and parietal cortex, and cerebellum. NOS activity was measured in the
hypothalamus by the arginine/citrulline assay. A significant decrease of NMDA
analog binding was found in the hypothalamus from old rats as compared with adult
(-66%) and immature animals (-57%), accompanied by a reduction in NMDAR content (
34% and -46%, respectively). NOS activity in the hypothalamus was 67% and 100%
higher in old rats as compared with the other two groups, although no significant
differences were observed in nNOS content. However, hypothalamic iNOS increased
3.8- and 7.6-fold in old rats, as compared with adult and immature, respectively.
This increase in hypothalamic iNOS was paralleled by a rise of iNOS in other
brain regions of old rats as compared respectively to adult and immature animals:
3.9- and 12.8-fold, in the frontal cortex; 2.8- and 2.5-fold, in the parietal
cortex; and 3.1- and 4.8-fold, in the cerebellum. These results show that aging
in this rat model is associated with high NO synthesis in the hypothalamus and
other regions of the brain, which is independent of the NMDAR/nNOS cascade. We
speculate that increased brain levels of iNOS may lead to neurotoxicity, which
may be involved in GnRH impaired pulsatile secretion, as well as acting as a
possible inducer of age associated neuronal loss in cognitive related brain
areas.
PMID- 9645702
TI - The arcuate nucleus is the major source for neuropeptide Y-innervation of
thyrotropin-releasing hormone neurons in the hypothalamic paraventricular
nucleus.
AB - Neuropeptide Y (NPY) immunoreactive (-ir) nerve fibers densely innervate
hypophysiotropic TRH perikarya and dendrites in the hypothalamic paraventricular
nucleus (PVN). To evaluate the contribution of the arcuate nucleus (Arc) to this
innervation, the effect of Arc ablation by neonatal monosodium glutamate (MSG)
treatment on the density of NPY-fibers contacting TRH neurons in the PVN was
investigated. After the lesioned animals and vehicle-treated controls reached
adulthood, the number of contacts between NPY-ir boutons and TRH-ir perikarya in
the PVN was determined in double-immunostained sections. In controls, numerous
contacts between NPY-ir terminals and TRH perikarya and dendrites were observed,
confirming earlier findings. MSG treatment resulted in a marked reduction of the
size of the Arc and also the number of NPY-perikarya with a concomitant reduction
of 82.4 +/-2.1% in the relative number of NPY terminals contacting TRH perikarya
and first order dendrites in the medial parvocellular and periventricular
subdivisions of the PVN. In contrast, lesioning of the ascending adrenergic
bundle in the brain stem caused no statistically significant change in the number
of NPY-terminals in close apposition to hypophysiotropic TRH neurons in the PVN.
These data confirm earlier findings that NPY-containing axon terminals innervate
TRH neurons in the PVN and further demonstrate a potentially important anatomical
relationship between NPY-producing neurons in the Arc and hypophysiotropic TRH
neurons.
PMID- 9645703
TI - Structure of the rat inhibin and activin betaA-subunit gene and regulation in an
ovarian granulosa cell line.
AB - We have isolated the rat inhibin and activin betaA-subunit gene, which is
composed of three exons, and have characterized a 571-bp region upstream from the
transcriptional start site that functions as a promoter in transient transfection
studies in an ovarian granulosa cell line, GRMO2. Deletion analysis of the 571-bp
promoter region has identified DNA sequences between -362 bp and -110 bp to be
essential in mediating basal promoter activity and activation by forskolin (FSK)
and/or 12-O-tetradecanoylphorbol-13-acetate (TPA). Within this region, a variant
CRE (cAMP response element) has been identified at -120 bp. Point mutations in
the variant CRE substantially reduce the ability of FSK and/or TPA to induce
promoter activity in GRMO2 cells. A single nucleotide change in the variant CRE,
which converts it to a consensus CRE, does not enhance promoter activity in
response to FSK and/or TPA, but rather reduces promoter activity to the same
extent as the other inactivating mutation in the variant CRE, suggesting that
this element does not act as a classical CRE. Consistent with this,
electrophoretic mobility shift assays performed using antibodies to a variety of
cAMP and phorbol ester-responsive transcription factors indicate that the AP-1
family proteins jun-B and fos-B are present in the protein complex binding to the
variant CRE. Overexpression of jun-B and fos-B in GRMO2 cells resulted in a
robust activation of the betaA-subunit promoter. Our results suggest that this
novel variant CRE sequence mediates both cAMP and phorbol ester regulation
through its interactions with AP-1family proteins.
PMID- 9645704
TI - Characterization of the testis and epididymis in mouse models of human Tay Sachs
and Sandhoff diseases and partial determination of accumulated gangliosides.
AB - Beta-hexosaminidase (Hex) is an essential lysosomal enzyme whose activity is
higher in the epididymis than in other tissues. The enzyme is also present in
sperm and has been postulated to be required for fertilization. To better
understand the role of Hex in reproduction, we have examined the testes and
epididymides of mouse models of human Tay Sachs and Sandhoff diseases, produced
by targeted disruption of the Hexa (alpha-subunit) or Hexb (beta-subunit) genes,
respectively, encoding the enzymes Hex A (structure, alphabeta) and Hex B
(betabeta). Testis weight, morphology, and sperm counts were unaffected in Hex
deficient mice. In the epididymis of the Hex A-deficient Hexa-/- mice, there was
a large increase in the size and number of lysosomes in the initial
segment/intermediate zone. In Hexb-/- mice (Hex A and B-deficient), the
epididymal defects were much more extensive and the cytoplasm of all cell types
throughout the efferent ducts and epididymis was filled with pale, uncondensed,
enlarged lysosomes. In contrast to the brain where GM2 ganglioside accumulates,
both mutant mice accumulated two non-GM2 gangliosides in the epididymis. The
major accumulated species was characterized by electrospray ionization tandem
mass spectrometry. The Hexa-/- male mice were fertile; however, litter sizes were
reduced. The Hexb-/- males were able to sire normal sized litters up to nine
weeks of age and remained healthy until 16-20 weeks of age. The extensive
abnormalities in the Hexb-/- mice, in contrast to region-specific effects in the
Hexa-/-mice, indicate an important and novel role for the Hex B isozyme in the
epididymis and a region-specific role for Hex A in the initial
segment/intermediate zone. In contrast to other reports, our results indicate
that Hex is not essential for fertilization in young adult male mice. To explain
the extensive epididymal abnormalities in the Hexb-/- mice, we propose that
substrates for Hex, such as testis-derived glycolipids, cannot be catabolized and
accumulate in lysosomes, leading to epididymal dysfunction and abnormalities in
the epididymal luminal environment that supports sperm maturation.
PMID- 9645705
TI - Genetic rescue of follicle-stimulating hormone beta-deficient mice.
AB - FSH is an alpha:beta heterodimeric pituitary glycoprotein that shares a common
alpha-subunit with LH and TSH. To study the role of FSH in mammalian
reproduction, we have previously generated an FSH-deficient mouse model using
embryonic stem (ES) cell technology by introducing a null mutation in the unique
FSHbeta gene. Male mice deficient in FSH are fertile despite their small testes
and reduced sperm number and motility. In contrast, FSH-deficient female mice are
infertile due to a block in folliculogenesis at the preantral stage. In this set
of experiments, we have rescued the mutant phenotypes of FSHbeta-deficient mice
by two genetic strategies. In the type I rescue mice, we introduced into the
FSHbeta-deficient background a 10-kb human FSHbeta transgene that is selectively
expressed in pituitary gonadotropes. The presence of this transgene [and thus the
interspecies hybrid (i.e. mouse alpha:human FSHbeta hormone)] in the background
of mouse FSHbeta deficiency completely restored the testis size, sperm number,
and motility defects to levels comparable to those seen in control male mice. All
of the mouse FSHbeta-deficient female mice carrying this human FSHbeta transgene
resumed normal folliculogenesis, were fertile and delivered normal size litters.
In the type II rescue mice, human FSH (human alpha:human FSHbeta) was ectopically
produced from multiple tissues in the mutant background using a mouse
metallothionein-I promoter. Whereas ectopic production of human FSH completely
rescued the mouse FSHbeta-deficient male mice, only 3 out of 10 mouse FSHbeta
deficient females bearing these human FSH transgenes were fertile and carried
their pregnancies to term and parturition. We conclude that the resultant
phenotypes due to a genetic deficiency of mouse FSHbeta can be corrected by
appropriate expression of human FSH transgenes and that human FSHbeta gene
regulation and function in the mouse pituitary are indistinguishable from the
endogenous mouse FSHbeta gene.
PMID- 9645706
TI - Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of
local insulin-like growth factor (IGF)-I production and expression of GH- and IGF
I-receptor in cultured rat chondrocytes.
AB - Growth depression as a side effect of glucocorticoid therapy in childhood is
partially mediated by alterations of the somatotropic hormone axis. The
mechanisms of interaction between glucocorticoids and somatotropic hormones on
the cellular and molecular level are poorly understood. In an experimental model
of primary cultured rat growth plate chondrocytes, basal as well as GH (40 ng/ml)
or insulin-like growth factor (IGF)-I (60 ng/ml)-stimulated growth was suppressed
dose dependently (10(-l2)-10(-7)M) by dexamethasone (Dexa). An IGF-I antibody
specifically and dose dependently inhibited the GH- but not the basic fibroblast
growth factor (bFGF)-stimulated cell proliferation. GH increased the IGF-I
concentration in conditioned serum-free culture medium; this was reversed by
concomitant Dexa. Dexa time dependently suppressed the transcription of GH
receptor (GHR) messenger RNA (mRNA) and down-regulated the basal and GH
stimulated expression of GHR. Whereas no suppressive effect on basal type I IGF
receptor (IGFR) was observed, Dexa blocked the IGF-I induced increase of IGF
binding. These results were confirmed by GHR and IGFR immunostaining. We conclude
that Dexa impairs the GH-induced stimulation of local secretion and paracrine
action of IGF-I and reduces the homologous increase of IGFR and GHR expression.
The above experiments give further insight on the interaction between GH and
glucocorticoids on the cellular and molecular level of growth plate chondrocytes.
PMID- 9645707
TI - Induction of ectopic corticotropic tumor in mouse embryos by exo utero cell
transplantation and its effects on the fetal adrenal gland.
AB - To establish an in vivo experimental system for developmental endocrinology
research, AtT-20 cells, a corticotropic tumor cell line, were transplanted by exo
utero manipulation into mouse embryos on embryonic day 14. The induced tumor
secreted ACTH in situ, and the circulating ACTH level was elevated. This was the
first model for studying the regulation of ACTH in the mouse fetal adrenal in
vivo and the first continuous ACTH treatment model in rodent fetuses. The changes
in the adrenal gland from the tumor-induced embryos were analyzed by light
microscopic morphometry, immunohistochemistry for steroidogenic enzymes, and
electron microscopy. In the treated adrenal, the volume of the inner cortical
zone was significantly larger than that in controls. In the inner zone, cell
density was decreased, and average cell size was increased, whereas
bromodeoxyuridine-incorporation was not increased. The enlarged inner zone cells
expressed an enhanced level of cytochrome P45011beta, the corticosterone
synthesizing enzyme, and the serum corticosterone level was increased. Electron
microscopy showed an active form of the organelles involved in steroidogenesis.
These findings indicate that ACTH stimulates both adrenocortical hypertrophy and
steroidogenesis in fetal mice. Potential perspectives of the novel paradigm in
this research for molecular developmental endocrine study are discussed.
PMID- 9645708
TI - Cloning of a membrane-spanning protein with epidermal growth factor-like repeat
motifs from adrenal glomerulosa cells.
AB - The three zones of adrenal cortex are thought to arise from a single
multipotential stem cell, but the mechanisms underlying the zonal differentiation
during embryonic development of adrenal cortex are poorly understood. Employing
subtraction cloning strategy, we isolated three distinct clones that were
specifically expressed in the rat glomerulosa zone. One clone, named zona
glomerulosa specific clone, encoded a membrane-spanning protein with a signal
peptide at the N-terminus, six epidermal growth factor-like repeat motifs, and a
transmembrane domain near the C-terminus. It was identified as a rat homolog of
preadipocyte factor-1 (Pref-1), a factor involved in maintaining the
undifferentiated status of preadipocyte. Immunohistochemical studies confirmed
the presence of Pref-1 protein in the glomerulosa zone. Detailed examination
revealed that the zone is divided into two layers; the first is a few-cells-thick
layer present underneath the capsule (expressing both Pref-1 protein and
aldosterone synthase cytochrome P450), and the second layer is beneath the first
(containing Pref-1 protein but not aldosterone synthase). Moreover, another cell
layer was found beneath the second layer and above the fasciculata zone, whose
cells contained no Pref-1 protein, aldosterone synthase, or 11beta-hydroxylase.
These findings suggest that a recently reported aldosterone synthase- and 11beta
hydroxylase-less cell layer between the two zones is composed of two kinds of
cell: Pref-1 protein-positive and -negative cells. The level of Pref-1 message in
the adrenal glands of animals having various pituitary-adrenal axis activities,
as well as various plasma salt concentrations, correlated with the total number
of glomerulosa cells. However, the specific content of Pref-1 message in a cell
was fairly constant. When the adrenal gland was surgically enucleated and the
remaining capsule regenerated, the level of Pref-1 transcript was significantly
suppressed at the early phase. At this phase, only a minor population of the
cortical cells expressed Pref-1 protein, most of these cells already expressing a
fasciculata/reticularis-specific marker, inner zone antigen. These findings
suggest that the capsular cells, mostly composed of the glomerulosa cells, may
have potential for differentiating into other zones' cells, and the down
regulation of Pref-1 expression may be an important step in the adrenal zonal
differentiation.
PMID- 9645709
TI - Pregnancy increases soluble and particulate guanylate cyclases and decreases the
clearance receptor of natriuretic peptides in ovine uterine, but not systemic,
arteries.
AB - Pregnancy increases uterine blood flow by 30- to 50-fold and uterine production
of cGMP by 38-fold. Moreover, cGMP causes potent vasodilatation. We hypothesized
that pregnancy up-regulates soluble and particulate guanylate cyclases (sGC and
pGC) in ovine uterine arteries. Activities of sGC and pGC were compared by
measuring cGMP production (37 C; 10 min) by uterine arteries from nonpregnant (n
= 5) and pregnant (n = 4, 120 +/- 2 days' gestation; term = 145 +/- 3 days; mean
+/- SE) ewes after sodium nitroprusside (100 microM), atrial natriuretic peptide
(1 microM), or C-type natriuretic peptide (CNP; 1 microM) treatment. The protein
and/or messenger RNA expressions of sGC beta1-subunit, pGC-A, pGC-B, the
clearance receptor of natriuretic peptide (CR), and CNP were investigated in
uterine and systemic (renal and/or omental) arteries from nonpregnant (n = 29)
and pregnant (n = 21; 125 +/- 2 days' gestation) ewes. The potencies of uterine
arterial GC activities were sGC >> pGC-A > pGC-B. Activities as well as protein
expression of sGC, pGC-A, and pGC-B in pregnant uterine arteries were increased
48-128% above those in nonpregnant controls concomitant with a 34% down
regulation of CR protein expression; systemic arterial protein expressions were
unaltered. These changes in uterine arterial GC-B and CR were confirmed using RT
PCR. Immunohistochemical staining of CNP in uterine, but not systemic, arterial
endothelium from pregnant ewes was much stronger than that from nonpregnant ewes.
Thus, two distinct GC pathways are present in ovine uterine artery, and both may
be specifically upregulated during pregnancy and so contribute to the tremendous
local increase in cGMP production during pregnancy.
PMID- 9645710
TI - Simian virus 40 T antigen-induced gonadotroph adenomas: a model of human null
cell adenomas.
AB - The cell of origin of human null cell pituitary adenomas is disputed. Although
these tumors, by definition, do not produce any of the anterior pituitary
hormones in vivo, they have been shown to express gonadotropin subunit genes,
release gonadotropin hormones in vitro, and express the gonadotroph-associated
transcription factor steroidogenic factor-1. However, they demonstrate variable
responses to releasing hormones in vitro, raising questions about their origin
from differentiated gonadotrophs or pluripotent stem cells. In this set of
experiments, transgenic mice carrying a temperature-sensitive mutant (TSA58) of
simian virus 40 T antigen driven by human FSHbeta regulatory elements were
produced. These animals developed slow growing, multifocal pituitary nodules that
demonstrated secretion of FSH with serum FSH levels 10-fold higher in male
transgenic animals and 5-fold higher in female transgenic animals than those in
nontransgenic controls. Anterior pituitary pathology progressed from diffuse
gonadotroph hyperplasia to nodular adenomas with persistent, but decreasing,
immunoreactivity for FSHbeta and LHbeta. Ultrastructural characteristics of the
tumors were identical to those of human null cell adenomas. These results support
the hypothesis that human null cell adenomas are derived from gonadotrophs and
provide an animal model for further study of this disease.
PMID- 9645711
TI - Follicle stimulating hormone (FSH) activates the p38 mitogen-activated protein
kinase pathway, inducing small heat shock protein phosphorylation and cell
rounding in immature rat ovarian granulosa cells.
AB - This study investigates the possibility that FSH activates the p38 mitogen
activated protein kinase (MAPK) pathway in immature granulosa cells (GC). FSH
induced the phosphorylation (activation) of p38 MAPK as evaluated by
immunoprecipitation and by phosphorylation-specific immunoblotting. FSH-induced
phosphorylation of p38 MAPK was blocked by pretreatment with the protein kinase A
(PKA) inhibitor H89 and mimicked by the cAMP generating agonist forskolin,
indicating that FSH-induced cAMP production and PKA activation are necessary and
sufficient for the activation of p38 MAPK in GC. The small heat shock protein HSP
27 comprises a downstream phosphorylation target for the p38 MAPK pathway. FSH
induced phosphorylation of HSP-27 was blocked by pretreatment with the p38 MAPK
inhibitor SB 203580, indicating that p38 MAPK activation is necessary for FSH
induced HSP-27 phosphorylation. FSH-induced GC rounding/aggregation was blocked
by pretreatment with SB 203580 indicating that p38 MAPK activation is necessary
for FSH-induced GC cell shape change. The results of these experiments show that
the p38 MAPK pathway is activated in GC in response to FSH in a cAMP/PKA
dependent manner, and that p38 MAPK activity is required for FSH-induced HSP-27
phosphorylation as well as rounding/aggregation in GC.
PMID- 9645712
TI - A corticotropin-releasing hormone type I receptor antagonist delays parturition
in sheep.
AB - In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release
of ACTH to produce a cortisol surge which leads to the onset of parturition. We
tested the hypothesis that fetal CRH is a primary factor in the onset of
parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to
block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days
of gestation. Five catheters were placed into the amniotic sac, fetal femoral
artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5
days' recovery, blood samples from maternal and fetal vessels were collected at
the following times: a day before the start of infusion, at [-1, 0, 1, 2, 4, 8
and 24]h, on the first day of infusion, and thereafter daily throughout a 10-day
infusion. Animals (n=6 per group) received infusions into a fetal vein of either
a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil
(Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The
plasma samples were assayed for ACTH and cortisol using commercial RIA kits.
Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9
days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036,
unpaired Student's t-test). Fetal ACTH and cortisol did not change in the
antalarmin-infused sheep after 3 days' infusion compared to significant increases
in vehicle-infused sheep (P=0.004 and P = 0.016 respectively, ANOVA). These data
show that CRH receptor antagonism in the fetus can delay the onset of
parturition. It supports the hypothesis that hypothalamic CRH drives fetal
production of ACTH and is essential for the onset of parturition triggered by a
surge in fetal cortisol.
PMID- 9645713
TI - Interleukin-1beta regulates pituitary follistatin and inhibin/activin betaB mRNA
levels and attenuates FSH secretion in response to activin-A.
AB - Activins and follistatins regulate all levels of the reproductive axis, including
the pituitary where they stimulate and inhibit FSH production, respectively.
Gonadotropes are known to express inhibin/activin betaB and activin-B
(betaBbetaB) functions as an autocrine modulator of FSH production. By contrast,
the mRNA for the activin-binding protein, follistatin, is present in most
pituitary cells and folliculo-stellate cells may be the major source of the
protein secreted by the anterior pituitary. Interleukin-1beta (IL-1beta) is one
of several cytokines known to also influence the reproductive axis. IL-1beta
inhibits the hypothalamo-pituitary-gonadal (HPG) axis by suppressing GnRH and
gonadal steroid production. Because several pituitary cell types, including
follistatin-producing folliculo-stellate cells, are targets of IL-1beta, cytokine
effects on gonadotrope function were evaluated using cultured rat anterior
pituitary cells. Activin-A (0.01 to 1 nM; 24h) increased basal FSH secretion
approximately 2-fold. IL-1beta (0.005 to 0.5 nM) by itself had no effect on basal
FSH secretion. However, IL-1beta attenuated FSH secretion in response to all
concentrations of activin-A. These results suggest that the cytokine might
stimulate the local production of a factor, such as follistatin, that antagonizes
the action of activin-A. RNase protection analysis indicated that IL-1beta (0.005
to 5 nM) stimulated follistatin and inhibin/activin betaB mRNA accumulation in a
time-dependent manner. These in vitro effects of IL-1beta were blocked by the
specific IL-1 receptor antagonist (IL-lra) and were not mimicked by either rhIL-6
or lipopolysaccharide (LPS). Treatment of intact male rats with LPS (50 microg,
i.v.), which increases plasma IL-1beta and induces IL-1beta expression in many
tissues, including the pituitary, produced similar time-dependent increases in
pituitary follistatin and inhibin/activin subunit mRNA levels. These results
suggest that IL-1beta can modulate gonadotrope responses to activins by
influencing the local balance of activin-B and follistatin within the pituitary.
PMID- 9645714
TI - Histopathologic characteristics of uveal melanomas in eyes enucleated from the
Collaborative Ocular Melanoma Study. COMS report no. 6.
AB - PURPOSE: To describe the principal histopathologic findings in a series of 1,527
globes with uveal melanoma and the relationship of these findings to each other.
METHODS: All eyes enucleated in the Collaborative Ocular Melanoma Study (COMS)
were examined independently by three ophthalmic pathologists and the findings
recorded on a data form. A composite of findings was obtained after adjudication.
RESULTS: The diagnosis was choroidal melanoma in 1,527 (99.7%) of 1,532 cases
examined. Misdiagnoses were metastatic adenocarcinoma (four) and hemangioma
(one). Spindle cell (9.0%), mixed cell (86.0%), and epithelioid cell (5.0%) types
were observed. Medium tumors were located more posteriorly than large tumors.
Considerable local invasion was seen: rupture of Bruch's membrane (87.7%),
invasion of the retina (49.1%), tumor cells in the vitreous (25.2%), vortex vein
invasion (8.9%), invasion of tumor vessels by tumor cells (13.8%), and invasion
into emissary canals (55.0%). Overall, 81.1% demonstrated local invasion,
excluding rupture of Bruch's membrane. Scleral invasion was present in 55.7% of
eyes, and extrascleral extension was present in 8.2%. Mitotic activity was
significantly reduced in eyes that had received preenucleation radiation
treatment (P < .001). The number of macrophages in the tumor increased with
increased pigmentation (P < .001) and increased necrosis (P < .01). CONCLUSION:
The accuracy of diagnosis in the COMS is high, with histopathologic confirmation
of the diagnosis at 99.7%. Extensive local invasion of the tumor was seen.
Preenucleation irradiation significantly reduced the number of mitotic figures.
An association was found regarding the presence of macrophages, the level of
pigmentation, and degree of necrosis.
PMID- 9645715
TI - The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre
enucleation radiation of large choroidal melanoma I: characteristics of patients
enrolled and not enrolled. COMS report no. 9.
AB - PURPOSE: To describe the baseline characteristics and status of patients enrolled
in the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of
pre-enucleation radiation of large choroidal melanoma conducted in the United
States and Canada, and to compare characteristics of patients enrolled with those
of patients with tumors of eligible size who were not enrolled in order to assess
the generalizability of findings from the clinical trial. METHODS: For all
patients evaluated for the clinical trial at COMS centers from November 1986
through December 15, 1994, selected data were transmitted to the COMS
Coordinating Center. For patients who enrolled in the clinical trial, ophthalmic
and medical history, examination findings, and visual acuity measurements were
recorded prior to enrollment. Standardized A-scan and contact B-scan echographic
examinations were performed prior to enrollment, and photoechograms were
submitted for central review for consistency with the diagnosis, independent
measurement of the apical height of the tumor, and description of tumor
configuration and internal reflectivity for each patient enrolled. Until January
1992, wide-angle fundus photographs and fluorescein angiograms taken prior to
enrollment also were submitted for central review to confirm consistency with the
diagnosis. All data were integrated and analyzed at the COMS Coordinating Center.
RESULTS: Of 6,078 patients with choroidal melanoma evaluated in COMS centers,
1,860 had tumors of eligible size; of these, 1,302 (70%) were eligible for the
clinical trial, and 1,003 (77% of eligible patients) enrolled. The two principal
reasons for ineligibility were other primary cancer and predominantly ciliary
body melanoma. Ineligible patients were older than eligible patients, had larger
choroidal melanoma, and had poorer visual acuity at the time of evaluation for
the COMS (P < .01, Wilcoxon rank sum tests). Patients eligible for the clinical
trial had a mean age of 60 years; 56% were male; almost all (97%) were non
Hispanic whites. Among eligible patients, mean tumor apical height was 9.5 mm and
mean longest basal diameter was 17.2 mm. Eligible patients who enrolled in the
trial were similar to eligible patients who did not enroll with respect to most
factors considered. Those who enrolled had longer tumor basal diameter and better
visual acuity in the fellow eye, more often had their primary residence in
Canada, and less often had education beyond high school than did eligible
patients who did not enroll (P < .05, Wilcoxon rank sum tests and chi2 tests,
respectively). CONCLUSIONS: The COMS clinical trial of pre-enucleation radiation
was designed to yield internally valid treatment comparisons through random
treatment assignment at time of enrollment. Findings also have high external
validity because a majority (54%) of all patients with tumors of eligible size,
and a large majority (77%) of all eligible patients, were enrolled. Furthermore,
patient characteristics are similar to those of patients included in other
evaluations of this method of treating large choroidal melanoma. Thus, findings
from this clinical trial apply to all patients who have large choroidal melanoma
and satisfy COMS eligibility criteria.
PMID- 9645716
TI - The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre
enucleation radiation of large choroidal melanoma II: initial mortality findings.
COMS report no. 10.
AB - PURPOSE: To report initial mortality findings from the Collaborative Ocular
Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of
large choroidal melanoma. METHODS: Patients were evaluated for eligibility at one
of 43 participating centers in the United States and Canada. Eligible consenting
patients were assigned randomly at the time of enrollment to standard enucleation
or to external radiation of the orbit and globe prior to enucleation. Eligibility
was confirmed at the COMS Coordinating Center, Echography Center, and Photograph
Reading Center. Adherence to the radiotherapy protocol was monitored at the
Radiological Physics Center. The diagnosis of choroidal melanoma was confirmed
following enucleation by a three-member Pathology Review Committee. Patient
accrual began in November 1986 and was completed in December 1994; 1,003 patients
enrolled. Patients have been followed at annual clinical examinations. Cause of
death was coded by a Mortality Coding Committee whose members were not involved
in the care of COMS patients; the clinical trial was monitored by an independent
Data and Safety Monitoring Committee. RESULTS: A total of 1,003 patients were
enrolled; 506 were assigned to enucleation alone and 497 to pre-enucleation
radiation. Treatment groups were well balanced on baseline characteristics. Only
nine patients were found to be ineligible after enrollment, seven in the interval
between randomization and enucleation and two after enucleation based on
histopathology. All but nine patients were treated as assigned; in only six of
491 eyes treated with pre-enucleation radiation was there a major deviation from
the radiotherapy protocol. With 5-year outcome known for 801 patients enrolled
(80%), the estimated 5-year survival rates and 95% confidence intervals (CIs)
were 57% (95% CI, 52% to 62%) for enucleation alone and 62% (95% CI, 57% to 66%)
for pre-enucleation radiation. Among the baseline covariates evaluated, only age
and longest basal diameter of the melanoma affected the prognosis for survival to
a statistically significant degree. The risk of death among patients treated with
pre-enucleation radiation relative to those treated with enucleation alone after
adjustment for baseline characteristics of patients, eyes, and tumors was 1.03
(95% CI, 0.85 to 1.25). Of 435 deaths classified by the Mortality Coding
Committee, 269 patients had histologically confirmed melanoma metastases at the
time of death. Estimated 5-year survival rates for this secondary outcome were
72% (95% CI, 68% to 76%) for enucleation alone and 74% (95% CI, 69% to 78%) for
pre-enucleation radiation. CONCLUSIONS: No survival difference attributable to
pre-enucleation radiation of large choroidal melanoma, using the COMS
fractionation schedule, has been demonstrated to date in this randomized trial.
The trial had statistical power of 90% to detect a relative difference in
mortality rates between the two treatment arms of 20% or larger. A smaller
difference is possible, but a clinically meaningful difference in mortality
rates, whether from all causes or from metastatic melanoma, is unlikely.
PMID- 9645717
TI - Combined analysis of two studies using the conjunctival allergen challenge model
to evaluate olopatadine hydrochloride, a new ophthalmic antiallergic agent with
dual activity.
AB - PURPOSE: To evaluate the effectiveness and safety of olopatadine hydrochloride
and to determine its optimal concentration and the onset and duration of action
for treating allergic conjunctivitis. Olopatadine is a new topical ophthalmic
antiallergic agent that demonstrates activity as both an antihistamine and a mast
cell stabilizer. Two double-masked, randomized, placebo-controlled, contralateral
eye comparison studies were conducted using the conjunctival allergen challenge
model. METHODS: A total of 169 subjects received 0.05% or 0.1% olopatadine. Study
subjects were healthy adult men and women with a history of active allergic
conjunctivitis within the previous two seasons but not receiving current
treatment. With an allergen dose that produced signs and symptoms of allergic
conjunctivitis at visits 1 and 2, the conjunctival allergen challenge was
performed 27 minutes after study drug administration at the third visit (onset-of
action challenge) and at 8 hours after study drug administration at the fourth
visit (duration-of-action challenge). Olopatadine was administered in one eye and
placebo in the opposite eye. Itching and redness were scored for both eyes at 3,
10, and 20 minutes after the conjunctival allergen challenge. RESULTS: Both 0.05%
and 0.1% concentrations of olopatadine were significantly (P < .05) more
effective than placebo in inhibiting itching and redness at all evaluations when
administered 27 minutes or 8 hours before the conjunctival allergen challenge.
There were no serious or drug-related ocular or nonocular adverse events in
either study. CONCLUSION: These findings demonstrate the rapid and prolonged (at
least 8 hours) ocular antiallergic action of olopatadine.
PMID- 9645718
TI - Local effects of previous conjunctival incisional surgery and the subsequent
outcome of filtration surgery.
AB - PURPOSE: Previous ocular surgery involving conjunctival incision is a risk factor
for failure of filtration surgery. To determine whether using adjunctive
antimetabolite therapy may have a rational basis, a study was performed to
determine whether the conjunctival cellular profile was altered by such surgery.
METHODS: After a mean follow-up of 5.9 years, filtration surgery outcomes for 35
patients who had undergone conjunctival incisional surgery were retrospectively
compared with 29 control and 18 matched patients who had not undergone such
surgery. At the time of filtration surgery, a conjunctival biopsy specimen was
obtained from all 82 patients, and these were quantitatively analyzed by light
microscopy in a prospective manner. RESULTS: Trabeculectomy success for the
control group (93%) was significantly higher than for the previous surgery group
(38%) (P < .001). Compared with control tissue, conjunctiva from the patients who
had undergone previous surgery contained more fibroblasts (P < .001, P < .05),
macrophages (P < .01, P < .001), and lymphocytes (P = .001, P < .01) in both
superficial and deep substantia propria (respective P values). Furthermore,
trabeculectomy failure was associated with an increase in number of conjunctival
fibroblasts in intraoperative specimens. CONCLUSIONS: Previous ocular surgery
involving the conjunctiva increases the number of conjunctival fibroblasts and
inflammatory cells. This may account for the increased risk of trabeculectomy
failure. Perhaps on this basis, the use of adjunctive medication may be justified
in patients who have undergone previous ocular surgery involving conjunctival
incision.
PMID- 9645719
TI - Identification of glaucoma-related visual field abnormality with the screening
protocol of frequency doubling technology.
AB - PURPOSE: To evaluate the predictive power of frequency doubling technology to
distinguish glaucoma suspects from persons with glaucoma visual field loss.
METHODS: A consecutive series of 76 subjects referred to a glaucoma service
underwent perimetry in one eye with frequency doubling technology in a screening
mode and Humphrey 24-2 threshold testing in random order, and had optic disk and
clinical nerve fiber layer grading. RESULTS: All subjects performed perimetry
with both instruments satisfactorily, with an average test time of 1.8 +/- 0.7
minutes per eye for the frequency doubling technology (instrument time). Of 33
eyes classified as abnormal by glaucoma hemifield test, 91% (30/33) were abnormal
on frequency doubling technology (two or more abnormal locations of 17), whereas
94% (31/33) of glaucoma suspects with normal Humphrey fields had normal results
with frequency doubling technology. Frequency doubling technology results were
highly correlated with Humphrey mean deviation by linear regression (r2 = .74, P
= .047) and with corrected pattern standard deviation probability value. A
frequency doubling technology error score for each quadrant of the field was
highly correlated with the number of severely abnormal points per quadrant in
Humphrey threshold tests (r2 = .63, P = .034). There was close agreement between
clinical examination of the optic disk and nerve fiber layer and frequency
doubling technology results. Three-level quantification of abnormality in
frequency doubling technology results did not add to diagnostic accuracy.
CONCLUSION: Frequency doubling technology testing shows promise as a screening
method in glaucoma.
PMID- 9645720
TI - Clinical classification of glaucomatous visual field loss by frequency doubling
perimetry.
AB - PURPOSE: To determine whether the frequency doubling perimeter (FDP) can grade
glaucomatous visual function loss in a clinically relevant manner. Sinusoidal
gratings < 1 cpd that undergo counterphase flicker > 15 Hz appear to have twice
as many bands of light, a phenomenon referred to as the "frequency doubling
illusion." Evidence suggests that this psychophysical effect is mediated in part
by large-diameter ganglion cells, which are reported to be lost early in the
glaucomatous disease process. A portable, commercially available FDP has already
demonstrated high diagnostic potential for glaucoma screening. METHODS: Sixty
four eyes of 42 glaucomatous patients and 22 eyes of 14 normal subjects were
evaluated by means of both frequency doubling perimetry and Humphrey perimetry. A
clinical scoring algorithm modeled after the Hodapp-Parrish-Anderson criteria for
scoring Humphrey visual field defects was derived for the FDP at the halfway
point of the study, and all participants were reassessed with this algorithm upon
its completion. RESULTS: FDP mean and pattern deviation showed strong linear
correlations with Humphrey 30-2 mean deviation (R = 0.75; P < .0001) and
corrected pattern standard deviation values (R = 0.64; P < .0001). Despite this,
neither global index could consistently categorize the graded glaucomatous visual
fields in a manner consistent with the Hodapp-Parrish-Anderson criteria. The new
FDP scoring algorithm did provide good segregation (73% precise parity, 93%
parity within one Humphrey grade). CONCLUSIONS: Sixteen-zone frequency doubling
perimetry can segregate glaucomatous visual field loss into pathologic categories
approximating those obtained with Humphrey 30-2 perimetry by means of a formula
modeled after the Hodapp-Parrish-Anderson criteria.
PMID- 9645721
TI - In vivo quantitative measurement of posterior capsule opacification after
extracapsular cataract surgery.
AB - PURPOSE: To introduce a new in vivo quantitative measurement of posterior capsule
opacification (PCO) after extracapsular cataract surgery and also to analyze the
correlation between opacification density and the patient's visual acuity.
METHODS: Prospectively, the opacification density value in the central 3-mm
portion of the posterior capsule was quantitated by means of an area densitometry
with the Scheimpflug photography system (EAS-1000). The EAS-1000 examination was
performed on 40 eyes with clinically significant PCO both before and after
undergoing Nd:YAG laser posterior capsulotomy, and on 10 eyes without PCO. The
correlation between the opacification density value and the visual acuity was
analyzed with a linear regression analysis. RESULTS: The mean opacification
density values +/- SD were 48.8 +/- 29.5 computer-compatible tapes (CCT) steps in
the PCO group before capsulotomy, 15.5 +/- 7.8 CCT steps in the PCO group after
capsulotomy, and 12.9 +/- 4.9 CCT steps in the non-PCO group. The mean
opacification density value in the PCO group before capsulotomy was significantly
greater than that in the PCO group after capsulotomy or than that of the non-PCO
group. A linear regression analysis determined that the opacification density
value also correlated well with the visual acuity (R2 = .808). CONCLUSIONS: We
have established a new in vivo quantitative measurement of PCO. Because the
opacification density value obtained by this measurement correlated well with the
patient's visual acuity, we consider this measurement to be useful in both the
research and clinical management of PCO.
PMID- 9645722
TI - Gelatinase B in proliferative vitreoretinal disorders.
AB - PURPOSE: To investigate whether gelatinases A and B are involved in the
pathogenesis of proliferative vitreoretinal disorders. METHODS: In a prospective
study of 101 consecutive patients, vitreous and paired serum samples were
obtained from 38 patients with rhegmatogenous retinal detachment complicated by
proliferative vitreoretinopathy, 25 patients with rhegmatogenous retinal
detachment with no proliferative vitreoretinopathy, and 38 patients with
proliferative diabetic retinopathy. Gelatinase activities were determined by
quantitative zymography. RESULTS: All vitreous samples contained comparable
levels of the constitutive gelatinase A. Inducible gelatinase B was detected in
eight (32%) of 25 vitreous samples from patients with rhegmatogenous retinal
detachment with no proliferative vitreoretinopathy (mean +/- SD, 319.5 +/- 521.0
scanning units), in 17 (44.7%) of 38 vitreous samples from patients with
proliferative vitreoretinopathy (560.6 +/- 718.9 scanning units), and in 34
(89.5%) of 38 vitreous samples from patients with proliferative diabetic
retinopathy (1,707.2 +/- 1,220.3 scanning units). The incidence of detection of
gelatinase B in proliferative diabetic retinopathy cases was significantly higher
than it was in rhegmatogenous retinal detachment with no proliferative
vitreoretinopathy and proliferative vitreoretinopathy cases (P < .001).
Gelatinase B levels in the vitreous samples of patients with proliferative
diabetic retinopathy were higher than the levels found in patients with
rhegmatogenous retinal detachment with no proliferative vitreoretinopathy and in
patients with proliferative vitreoretinopathy (P = .0152). Gelatinase A was
detected in all the tested sera, whereas none of the tested paired serum samples
contained detectable gelatinase B activity. CONCLUSIONS: Gelatinase B may play an
important role in extracellular matrix degradation associated with
neovascularization in proliferative diabetic retinopathy.
PMID- 9645723
TI - Delusions of ocular parasitosis.
AB - PURPOSE: To describe four cases of delusions of parasitosis in which self
inflicted ocular trauma occurred. Delusions of parasitosis is a somatic
delusional disorder in which patients have the irrational belief that their
bodies are infested by parasites or other infectious organisms. Self-inflicted
trauma can result from attempts to eliminate the supposed infestation. METHODS:
We reviewed the case histories of four patients (one male, three females, 35 to
45 years of age) who presented with complaints of ocular infestation but had no
evidence of infectious ocular disease. The characteristics of these cases were
compared with the features of delusions of parasitosis. RESULTS: All patients
maintained their beliefs regarding infestation, despite extensive clinical and
laboratory investigations that found no evidence of infectious diseases. Self
inflicted eye injury, associated with attempts to eliminate the infestation,
occurred in each case. CONCLUSIONS: The cases presented in this report are
consistent with a diagnosis of delusions of parasitosis. The eye can be a
principal focus of attention in this disorder, which may lead to vision loss
caused by self-inflicted injury.
PMID- 9645724
TI - Threshold perimetry of each eye with both eyes open in patients with monocular
functional (nonorganic) and organic vision loss.
AB - PURPOSE: To report a novel binocular perimetry test to identify monocular
functional vision loss. METHODS: In a prospective study, 10 patients with
monocular functional vision loss, 10 patients with monocular organic vision loss,
and 10 normal subjects were tested using a Humphrey automated perimeter
attachment that performs central threshold perimetry of both eyes in a single
test. First, patients were tested after being told their "good" (unaffected) eye
was being tested; this was followed by a second identical test said to be on the
"bad" (affected) eye. Two measurements were calculated for each subject: the
functional component (deltaF), defined as the difference (in dB) between the mean
threshold of the first and second tests, and the organic component (deltaO), the
difference (in dB) between the mean threshold of the unaffected and affected
eyes. RESULTS: Patients with monocular functional vision loss produced lower
thresholds when they thought their affected eye alone was being tested but little
intereye difference (mean deltaF +/- SD = 17.35 +/- 7.50 dB; mean deltaO = 0.01
+/- 1.40 dB). Patients with monocular organic vision loss had little difference
between tests and lower thresholds in their affected eye (mean deltaF = 0.84 +/-
1.15 dB; mean deltaO = 9.01 +/- 4.71 dB). Normal subjects demonstrated little
intertest or intereye differences (mean deltaF = -0.15 +/- 0.78 dB; mean deltaO =
-0.05 +/- 0.51 dB). CONCLUSION: This perimetry method effectively distinguished
between normal subjects, patients with monocular functional vision loss, and
patients with monocular organic vision loss.
PMID- 9645725
TI - Choroidal melanoma: diagnosis and management.
PMID- 9645726
TI - Histopathology of the eye in diffuse neonatal hemangiomatosis.
AB - PURPOSE: To report the ocular presentation and histopathology of a patient with
diffuse neonatal hemangiomatosis. METHODS: Case report. A 3.7-kg female was born
at term. Multiple hemangiomas were present, and the patient died 39 days after
birth. RESULTS: Widespread cutaneous and visceral hemangiomas were present.
Ophthalmic examination disclosed bilateral eyelid and conjunctival hemangiomas.
The right eye had multiple iris hemangiomas, hyphema, vitreous hemorrhage, and
discrete subretinal lesions. Histopathology of the right eye demonstrated
hemangiomas involving the iris, ciliary body, and ciliary processes. CONCLUSION:
Diffuse neonatal hemangiomatosis was associated with ophthalmic findings of
multiple hemangiomas involving eyelid, conjunctiva, iris, ciliary body, and
ciliary processes.
PMID- 9645727
TI - Cutaneous angiosarcoma with eyelid involvement.
AB - PURPOSE: To report a clinicopathologic correlation of angiosarcoma affecting the
eyelid skin. METHODS: An 82-year-old man developed multiple bruise-like
maculopapular lesions, subcutaneous nodules, and diffuse edema over his scalp,
face, and eyelids. Biopsy disclosed angiosarcoma, and the patient was treated
with wide-field external beam radiotherapy (5,000 cGy). RESULTS: He responded to
radiotherapy with partial regression of the tumor. Twelve months later, he
developed extensive lymphedema secondary to the residual tumor. He was also found
to have parotid gland and bone metastases, treated with radiotherapy. The patient
died of widespread bone metastases 3 months later. CONCLUSIONS: Angiosarcoma is a
rare skin tumor that has a poor prognosis despite treatment. It should be
considered in the differential diagnosis of eyelid tumors and edema because it
may affect only the central portion of the face.
PMID- 9645728
TI - Rifabutin-associated uveitis in an immunosuppressed pediatric patient without
acquired immunodeficiency syndrome.
AB - PURPOSE: To describe a case of bilateral, symptomatic rifabutin-associated
uveitis with hypopyon and vitreal opacities in an immunosuppressed pediatric
patient without acquired immunodeficiency syndrome (AIDS). METHOD: Case report.
An 8-year-old boy presented with bilateral uveitis 24 months after a bilateral
lung transplant. RESULTS: Our patient, whose medications included rifabutin,
clarithromycin, and immunosuppressive agents, responded to discontinuation of the
rifabutin and initiation of intensive topical corticosteroid therapy with
complete resolution of the uveitis. CONCLUSION: Rifabutin-associated uveitis may
occur in a non-AIDS pediatric patient.
PMID- 9645729
TI - Endogenous Candida endophthalmitis after induced abortion.
AB - PURPOSE: To report two young healthy women who developed endogenous Candida
endophthalmitis after undergoing surgically induced abortion. METHOD: Case
reports. RESULTS: In two eyes of two patients, a diagnosis of Candida
endophthalmitis was established by typical fundus appearance, positive vaginal
culture, and, in one case, positive vitreous culture. After vitrectomy and
intravitreal amphotericin B injection, one eye of one patient had a best
corrected visual acuity of 20/200, whereas one eye of one patient, who had
systemic corticosteroid treatment before the correct diagnosis, developed
recurrent retinal detachment and a best-corrected visual acuity of counting
fingers. CONCLUSIONS: Induced abortion may cause endogenous Candida
endophthalmitis in young healthy pregnant women. Systemic corticosteroid
treatment may increase the risk of endophthalmitis.
PMID- 9645730
TI - Bilateral multifocal choroidal carcinoid: long-term follow-up without treatment.
AB - PURPOSE: To report a minimally symptomatic patient with bilateral carcinoid
tumors metastatic to the choroid who was followed up for 42 months without any
treatment. METHOD: Case report. RESULTS: A 54-year-old white man with a history
of bronchial carcinoid tumor had bilateral multiple carcinoid tumors metastatic
to the choroid. Follow-up for 42 months without treatment demonstrated no growth
of the choroidal tumors, and corrected visual acuity remained RE, 20/20 and LE,
20/25. Systemic status also remained stable. CONCLUSIONS: Carcinoid tumors
metastatic to the choroid may remain stationary for an extended period. Treatment
may be deferred until tumor growth, exudative retinal detachment, or substantial
impairment of vision develops.
PMID- 9645731
TI - Percutaneous treatment of an orbital hydatid cyst: a new therapeutic approach.
AB - PURPOSE: To describe the percutaneous treatment of an orbital hydatid cyst as an
alternative approach to conventional surgery. METHODS: In a 21-year-old man with
diplopia and right proptosis, radiologic studies disclosed a 25 x 25 x 20-mm
purely cystic mass in the right retrobulbar area. Based on the presumptive
diagnosis of hydatid cyst, the cyst was treated percutaneously under
ultrasonographic guidance with aspiration, 15% hypertonic saline injection, and
reaspiration without any complication. RESULTS: A substantial decrease in the
size of the cyst was observed in the 3 months after treatment. Nine months after
treatment, the shrunken cyst had a volume of only 0.5 ml, and the patient was
asymptomatic. Twenty-one months after the procedure, the findings were consistent
with those at 9 months of follow-up. CONCLUSION: Percutaneous treatment of
orbital hydatid cysts, which is more satisfactory to both the patient and the
physician, may be a safe and effective alternative to surgical extirpation.
PMID- 9645732
TI - Pneumo-orbital cyst after orbital fracture repair.
AB - PURPOSE: To report a case of a respiratory epithelial-lined, air-filled orbital
cyst as a late complication of orbital fracture repair. METHOD: Case report.
RESULTS: Recurrent episodes of diplopia and hyperophthalmia developed secondary
to pneumatic inflation of a respiratory epithelial-lined orbital cyst 6 months
after orbital fracture repair. This cyst remained in communication with an
ethmoidal air cell and became inflated during pressurization of the ethmoid
sinus. Removal of the cyst and orbital implant was curative. CONCLUSION: Air
filled, respiratory epithelial-lined orbital cyst is a rare cause of episodic
diplopia and globe displacement after orbital trauma.
PMID- 9645733
TI - Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic
resonance imaging.
AB - PURPOSE: To describe the thin-slice magnetic resonance imaging features of
vascular compressive oculomotor nerve paresis. METHODS: We performed thin-slice
(2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman
with right partial oculomotor nerve paresis using spoiled gradient recalled
acquisition in the steady state. RESULTS: Thin-slice magnetic resonance images
disclosed that the right oculomotor nerve was compressed and dislocated
superiorly and laterally by the tortuous basilar artery. No other abnormalities
were observed. CONCLUSION: This is the first case report of vascular compressive
oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.
PMID- 9645734
TI - Severe vision loss and neovascular glaucoma complicating superior ophthalmic vein
approach to carotid-cavernous sinus fistula.
PMID- 9645735
TI - Bowel permeability is improved in Crohn's disease after ileocolectomy.
AB - PURPOSE: Numerous investigators have shown increased bowel permeability in
patients with Crohn's disease. It is unclear whether this is a precondition
affecting the entire intestine or a consequence of the inflammation and,
therefore, only affecting the diseased bowel. The present study tested the
hypothesis that resection of diseased bowel in patients with ileocolonic Crohn's
disease would correct abnormalities in bowel permeability. METHODS: Ten patients
(5 females; mean age, 33 +/- 2 years) with ileocolonic Crohn's disease who
underwent elective ileocolic resections had bowel permeability measured
preoperatively and postoperatively by the relative urinary clearance of orally
consumed lactulose and rhamnose. RESULTS: Mean preoperative bowel permeability in
patients with Crohn's disease was significantly elevated relative to healthy
volunteers (0.172 +/- 0.04 vs. 0.046 +/- 0.01; P < 0.05, unpaired t-test). After
ileocolectomy, bowel permeability decreased in patients with Crohn's disease and
reached a normal range by postoperative day 30. CONCLUSIONS: Bowel permeability
is increased in patients with ileocolic Crohn's disease because of the presence
of diseased bowel and decreases to a normal range in these patients after
resection of gross intestinal disease. This suggests that bowel permeability may
be a quantitative and clinically effective method with which to assess the
presence and severity of diseased bowel in patients with Crohn's disease.
PMID- 9645736
TI - Functional results after perineal complications of ileal pouch-anal anastomosis.
AB - PURPOSE: This study investigated the functional significance of perineal
complications after ileal pouch-anal anastomosis. METHODS: Review of a
prospective registry of 628 patients was undertaken. Bowel function was assessed
by detailed functional questionnaire. Statistical analyses were performed using
chi-squared and Fisher's exact probability tests. RESULTS: Of 628 patients, 153
(24.4 percent) had 171 perineal complications. The 277 control patients had no
complications. Complications included 66 (10.5 percent) anastomotic strictures,
28 (4.5 percent) anastomotic separations, 36 (5.7 percent) pouch fistulas, 41
(6.5 percent) episodes of pelvic sepsis, and 18 (2.9 percent) patients with
multiple complications. After these complications were addressed, the pouch
failure rate was low (10 percent); in 90 percent of patients, the pouch could be
salvaged. Most pouch failures were the result of pouch fistulas, and most
occurred in patients ultimately diagnosed with Crohn's disease. Functional
results after cure of these perineal complications revealed no significant
functional differences between control patients and those cured of anastomotic
separations, anastomotic strictures, and pouch fistulas. Only a few minor
differences were demonstrated in function after an episode of pelvic sepsis. The
major deterioration in function occurred after treatment for multiple perineal
complications. CONCLUSIONS: An appreciable number of perineal complications occur
after ileal pouch-anal anastomosis. Pouch-perineal fistulas are associated with
the highest pouch failure rate. The majority of these fistulas occur in patients
ultimately diagnosed with Crohn's disease or indeterminate colitis. Although
there is no substitute for good technique and sound clinical judgment in the
success of ileal pouch-anal anastomosis, if perineal complications are
successfully treated, functional outcome is equivalent to that in patients
without perineal complications.
PMID- 9645737
TI - Urinary retention after operations for benign anorectal diseases.
AB - PURPOSE: This study was undertaken to determine the incidence and risk factors
for urinary retention after operations for benign anorectal diseases. METHODS: We
reviewed 1,026 consecutive operations for benign anorectal diseases from 1989 to
1994. Risk factor analysis was done for patients undergoing hemorrhoidectomy
(Group I) and other procedures (Group II) using logistic regression analysis.
RESULTS: The number of procedures and urinary retention rate was as follows: 344
(34 percent) hemorrhoidectomies, 159 (2 percent) fistulotomies, 95 (5 percent)
incision/drainage, 247 (4 percent) lateral internal sphincterotomy, 181 (17
percent) combinations of the above four procedures, and overall 1,026 (16
percent). In Group I, four-quadrant excision (odds ratio, 3.3; P = 0.0004), three
quadrant excision (odds ratio, 2.4; P = 0.003), morphine equivalents >33 (odds
ratio, 1.8; P = 0.01), and male gender (odds ratio, 1.7; P = 0.02) were
independent risk factors. In Group II, more than one operation (odds ratio, 3.0;
P = 0.004), older age (odds ratio, 3.1; P = 0.005), intraoperative fluids (odds
ratio, 2.6; P = 0.03), and postoperative fluids (odds ratio, 2.7; P = 0.02) were
independent risk factors. Urinary obstructive symptoms for both groups and
perioperative fluids for Group I were NOT independent risk factors. Hospital stay
was prolonged significantly in patients with urinary retention (P = 0.0001).
CONCLUSIONS: Urinary retention is a common postoperative complication that
increases hospital stay. It is most common after hemorrhoidectomy. Disease
severity (quadrants excised and analgesia requirement for Group I and number of
operations for Group II) is an important risk factor for both groups studied.
Older age in Group I and perioperative fluid in Group II may be important risk
factors.
PMID- 9645738
TI - Perineal body measurement improves evaluation of anterior sphincter lesions
during endoanal ultrasonography.
AB - Endoanal ultrasonography has become an important tool in the evaluation of
patients with anal incontinence. However, the extent of anterior defects is
sometimes difficult to quantitate during endoanal ultrasonography. PURPOSE: This
study was designed to evaluate perineal body measurement during endoanal
ultrasonography in assessing patients with obstetric anal sphincter injuries.
METHODS: Forty-two patients with anal incontinence because of obstetric sphincter
injuries and 13 asymptomatic subjects were investigated with endoanal
ultrasonography. Sphincter muscle thickness, sphincter defects, and perineal body
were measured. Perineal body measurement was performed by inserting a finger,
held gently against the posterior vaginal wall, into the vagina and measuring the
distance between the inner surface of the internal sphincter and the
ultrasonographic reflection of the finger. RESULTS: All patients had anterior
sphincter lesions of varying extent. Mean size of internal sphincter lesions was
146 degrees, and mean size of external sphincter lesions was 107 degrees (P <
0.001). Perineal body measurement was performed without difficulty in all
patients and subjects. Perineal body measurement (mean +/- standard deviation)
was 6 +/- 2 mm in patients and 12 +/- 3 mm in asymptomatic subjects (P < 0.001).
Ninety-three percent of patients had perineal body measurement < or = 10 mm, and
70 percent of asymptomatic subjects had perineal body measurement > 10 mm.
Digital delineation of the perineal body during endoanal ultrasonography improved
the visualization of sphincter lesions in 74 percent of patients. CONCLUSIONS:
Digital delineation of the perineal body during endoanal ultrasonography improved
the visualization of sphincter lesions in the majority of patients. Perineal body
measurement is performed without difficulty and is a good predictor of anterior
sphincter lesions. Use of this technique improves visualization of sphincter
lesions.
PMID- 9645739
TI - Value of postoperative surveillance after radical surgery for colorectal cancer:
results of a cohort study.
AB - PURPOSE: Early detection of recurrence after curative resection for primary
colorectal cancer should improve patients' prognosis. However, the usefulness of
postoperative surveillance programs has not been clarified yet. The present
cohort study was aimed at assessing the effectiveness of systematic follow-up in
patients with colorectal cancer who were operated on for cure, regarding both
rate of tumor recurrence amenable to curative-intent surgery and rate of
survival. METHODS: One hundred ninety-nine colorectal cancer patients who
underwent radical primary surgery were followed according a well-defined
postoperative surveillance program, which consisted of laboratory studies
(including serum carcinoembryonic antigen assay) every three months, physical
examination and abdominal ultrasound or computed tomography every six months, and
chest radiograph and total colonoscopy once per year. Cohorts were defined
according to patients' compliance with the proposed follow-up program. A
multivariate regression model was constructed to predict survival. RESULTS: One
hundred forty patients were considered to be compliant with the surveillance
program, whereas the remaining 59 patients occasionally attended follow-up
investigations or did not comply at all. Although there were no differences in
the overall recurrence rate (38 vs. 41 percent; P = 0.52), curative-intent
reoperation was possible in 18 patients (34 percent) of those with tumor
recurrence in the compliant cohort but in only 3 patients (12 percent) in the
noncompliant cohort (P = 0.05). Similarly, the probability of survival was higher
in the compliant cohort, both regarding overall (63 vs. 37 percent at 5 years; P
< 0.001) and cancer-related (69 vs. 49 percent at 5 years; P < 0.02) rates. Cox
regression analysis disclosed that only a more advanced TNM stage (odds ratio,
8.17; 95 percent confidence interval, 1.13-59.29) and noncompliance with the
postoperative surveillance program (odds ratio, 2.32; 95 percent confidence
interval, 1.50-3.60) had an independent negative impact on survival. CONCLUSION:
Systematic postoperative surveillance in patients with colorectal cancer who were
operated on for cure increases both the rate of tumor recurrence amenable to
curative-intent surgery and rate of survival.
PMID- 9645740
TI - Cost-effectiveness of dynamic graciloplasty in patients with fecal incontinence.
AB - PURPOSE: This study evaluates the cost-effectiveness of dynamic graciloplasty for
intractable fecal incontinence. PATIENTS AND METHODS: The costs and effects of
dynamic graciloplasty were measured in a prospective, longitudinal study and in a
clinical trial. Forty-three patients with intractable fecal incontinence were
evaluated before and after dynamic graciloplasty. Costs were obtained from the
hospital information system and from patient-oriented questionnaires. We compared
the costs of a dynamic graciloplasty with the costs of a colostomy. Colostomy
costs were evaluated using a group of seven patients who had a stoma in place for
incontinence for several years. Sensitivity analyses were included. RESULTS:
Total direct costs of lifelong dynamic graciloplasty were $31,733 (United States
dollars), costs of lifelong conventional treatment were $12,180 (United States),
and costs of colostomy, including lifelong stoma care, were $71,576 (United
States). The clinical success rate of dynamic graciloplasty was 74 percent.
Quality of life after successful dynamic graciloplasty was better than with
conventional treatment. CONCLUSION: We found that dynamic graciloplasty was more
expensive than conventional treatment but resulted in a significantly higher
quality of life. Stoma treatment was the least attractive alternative regarding
both costs and effects. The Dutch Health Insurance Executive Board recommended
reimbursement for the dynamic graciloplasty procedure.
PMID- 9645741
TI - Which physiologic tests are useful in patients with constipation?
AB - PURPOSE: Physiologic tests such as manometry, colonic transit times, balloon
compliance, defecography, pudendal nerve latency, and electromyography are used
to evaluate patients with severe constipation. Patients referred because of
severe constipation between 1991 and 1996 were studied to examine the role that
physiologic testing played in making a diagnosis and directing treatment.
METHODS: Of 139 patients referred for severe idiopathic constipation, physiologic
testing was recommended in 127, and 104 patients underwent the studies. The
pretesting impression was noted, and test results were evaluated to determine
diagnostic accuracy. If a specific initial impression was documented, tests were
classified as refuting it, confirming it or confirming and adding significant
information. If there was no clear pretest impression, tests were evaluated for
their ability to indicate a diagnosis. The patient's history also was evaluated
to determine what information was most useful in making a diagnosis. Historical
features including duration of constipation, symptoms consistent with outlet
obstruction or dysmotility, age, associated urinary incontinence, and prior
hysterectomy were analyzed. Data were collected prospectively, then reviewed by
an independent observer. RESULTS: Ninety-eight study patients remained after 29
were excluded who did not undergo the recommended studies (19) or because no
initial impression was documented (10). In 43 patients (44 percent), testing did
not provide additional useful information. In 8 patients, testing confirmed the
initial impression and added information impacting the treatment plan. Test
results clearly refuted the initial impression in only one patient. In 46 (47
percent) patients the initial impression was uncertain, and in 43 (94 percent) of
these, testing aided in making the diagnosis. In three cases, the diagnosis
remained uncertain after testing. Prior hysterectomy (P = 0.003), urinary
incontinence (P < 0.001), and symptoms of pelvic outlet obstruction (P = 0.03)
were associated with a high incidence of rectocele. Defecography and transit
times were the most useful tests. Surprisingly, symptoms of outlet obstruction or
dysmotility did not show an overall correlation with transit times. CONCLUSIONS:
In one-half of these patients with severe constipation, physiologic testing added
significant information, leading to a specific diagnosis. Pretesting history and
symptoms did not predict which patients were most likely to benefit from these
studies.
PMID- 9645742
TI - Long-term functional evaluation of straight coloanal anastomosis and colonic J
pouch: is the functional superiority of colonic J-pouch sustained?
AB - AIM: This study was designed to analyze the functional and clinical outcomes of
straight coloanal anastomosis compared with colonic J-pouch performed after low
anterior resection. MATERIALS AND METHODS: Between September 1989 and June 1996,
all patients who underwent low anterior resection with anastomosis less than 4 cm
from the dentate line were classified into two groups based on the restoration of
intestinal continuity: "straight" coloanal anastomosis (n = 39) or colonic J
pouch (n = 44). Both groups were assessed according to the level of anastomosis,
anastomotic complications (stricture, leak, pelvic abscess), age, and gender. For
comparison of functional outcome, daily bowel movements, tenesmus, urgency,
incontinence score (range, 0-20), and anorectal manometric findings were
evaluated preoperatively and at six months, and one and two years after surgery.
RESULTS: There were no significant differences between the groups relative to
age: (coloanal anastomosis, 66.3 +/- 10.1 (range, 46-86), vs. colonic J-pouch,
64.9 +/- 13.2 (range, 39-88) years); gender (females): (coloanal anastomosis,
46.2 percent vs. colonic J-pouch; 38.6 percent); diagnosis: (rectal carcinoma:
coloanal anastomosis, 84.6 percent, vs. colonic J-pouch, 77.3 percent);
preoperative incontinence score (coloanal anastomosis, 1.5 +/- 4.6, vs. colonic J
pouch, 1.1 +/- 4); bowel movements: (coloanal anastomosis, 2.1 +/- 2.3, vs.
colonic J-pouch, 2.1 +/- 1.9/day); level of anastomosis: (coloanal anastomosis,
1.8 +/- 1.3, vs. colonic J-pouch, 1.5 +/- 1.3 cm from the dentate line); history
of perioperative radiation therapy: (coloanal anastomosis, 15.4 percent, vs.
colonic J-pouch, 20.5 percent); or manometric findings. There was also no
significant difference in postoperative mortality: (coloanal anastomosis, 5.1
percent, vs. colonic J-pouch, 2.3 percent); or anastomotic complications:
(coloanal anastomosis, 7/39 (17.9 percent), vs. colonic J-pouch, 2/44 (4.5
percent) P = 0.08); strictures: (10.3 vs. 0 percent); leaks: (5.1 vs. 2.3
percent); bleeding: (2.6 vs. 0 percent); rectovaginal fistula: (0 vs. 2.3
percent). Also, in the colonic J-pouch group, two patients developed pouchitis,
and one patient experienced difficult evacuation one year after surgery. There
was a statistically significant better function judged by less frequent bowel
movements (4 +/- 2 vs. 2.4 +/- 1.3/day; P < 0.005) and urgency (36.7 vs. 7.7
percent; P < 0.05), incontinence score (2.2 +/- 3.7 vs. 0.8 +/- 1.6; P < 0.05) up
to one year after surgery. At two years, the coloanal anastomosis group did not
show statistical improvement in functional results compared with one year
postoperatively. Rectal compliance in manometric findings was significantly
increased in the coloanal anastomosis group at one year after surgery (12.4 +/-
12.6 vs. 4.2 +/- 1.5 ml/mmHg; P < 0.05). However, these differences were less
profound after two years. CONCLUSION: The functional superiority of the colonic J
pouch was greatest at one year after surgery. By two years, adaptation of the
"straight" coloanal anastomosis yielded similar functional results. However, the
almost fourfold reduction in anastomotic complications in the colonic J-pouch
group reveals a second potential advantage of this technique.
PMID- 9645743
TI - Selective expression of carcinoembryonic antigen promoter in cancer cell lines:
targeting strategy for gene therapy in colorectal cancer.
AB - PURPOSE: This study was designed to characterize the mechanisms regulating the
expression of the human carcinoembryonic antigen promoter (pCEA), in terms of
tissue-specific targeting for gene therapy. The promoter was subcloned to a
luciferase reporter gene (pCEA/Luc) in our laboratory and compared with a virally
controlled luciferase vector (pSV40/Luc). METHODS: Four human cancer cell lines
(HeLa, SW480, Caco2, and SW1116) were transfected with either pCEA/Luc or
pSV40/Luc. Cells were treated with interferon-gamma and assayed at 72 hours after
treatment. Carcinoembryonic antigen level was measured by enzyme immunoassay.
Luciferase expression was measured at 48 hours and one week after transfection by
luminometry. RESULTS: Luciferase activity after transfection with pCEA/Luc was
higher in CEA-positive cells than in CEA-negative cells (P < 0.0001). pCEA/Luc
demonstrated higher activity than pSV40/Luc in CEA-positive cells (P < 0.0001),
but not in CEA-negative cells. In Caco2 cells, which before confluence are CEA
negative, luciferase expression increased on reaching confluence (P < 0.0001).
Well to moderately differentiated cells responded to the interferon-gamma
treatment, but the increase in CEA secretion did not correspond to an increase in
pCEA/Luc expression. CONCLUSIONS: The expression of pCEA correlates well with the
CEA production by the specific cell line offering a potential tissue-specific
targeting strategy for colon cancer gene therapy. Furthermore, the tissue
specific CEA promoter has a higher and more persistent activity in CEA-positive
human cancer cells than a viral promoter. The lack of response to interferon
gamma treatment suggests a different mechanism of action for interferon-gamma
other than directly interacting with the promoter.
PMID- 9645744
TI - DCC protein as a predictor of distant metastases after curative surgery for
rectal cancer.
AB - PURPOSE: The aim of this study was to determine the value of DCC (deleted in
colorectal cancer) protein for predicting metachronous distant metastases after
curative surgery for rectal cancer. The DCC protein--for which a gene has been
located on chromosome 18q--has recently been reported to have a prognostic value
in colorectal cancer. This finding might have implications for treatment of
International Union Against Cancer Stage II rectal carcinoma, in which distant
metastases will develop in 14 percent of patients despite optimal surgery.
METHODS: Paraffin-embedded tissues from 85 patients who developed distant
metastases, but no local recurrence, after curative surgery for rectal cancer
were matched with 85 samples from patients who remained disease-free. Matching
criteria were tumor stage, age, gender, and date of surgery. Expression of DCC
protein was assessed using immunohistochemistry. End points of follow-up were
recurrence of disease and death. Mean follow-up was 9.6 years. No patient
received either local or systemic adjuvant therapy. RESULTS: The DCC protein was
found to be expressed in 64.9 percent of tumor samples. Nonexpression of DCC
protein had an negative influence on survival (P = 0.03). For all tumor stages
together, sensitivity of the test for subsequent occurrence of distant metastases
was 42 percent and specificity was 71 percent. In Stage II cancers, the positive
predictive value was 19 percent, and the negative predictive value was 88
percent. CONCLUSIONS: Our results confirm that DCC protein is a useful prognostic
marker in patients with rectal carcinomas, but the positive predictive value of
DCC protein for occurrence of metachronous metastases does not appear to be
sufficient to justify adjuvant therapeutic measures in Stage II rectal cancer.
PMID- 9645745
TI - Limitation of endorectal ultrasonography: what does a low lesion more than 5 mm
in size correspond to histologically?
AB - PURPOSE: The accuracy of diagnosis of metastatic lymph nodes for rectal carcinoma
has not improved. A low echoic lesion more than 5 mm in size detected by
endorectal ultrasonography is preoperatively assessed as a metastatic lymph node.
What does a low echoic lesion more than 5 mm in size correspond to
histologically? METHODS: Forty-seven patients with lower rectal carcinoma (Term
I, 1986-1990) and 48 patients with lower rectal carcinoma (Term II, 1991-1995)
undergoing endorectal ultrasonography were reviewed. Surgically resected rectal
specimens from 40 patients with rectal carcinoma underwent ultrasonography. Low
echoic lesions more than 5 mm in size were taken from resected specimens and were
stained with hematoxylin, followed by histologic examination. RESULTS: The
accuracy of diagnosis of metastatic lymph nodes of Term II was not higher than
that of Term I. Twenty-five low echoic lesions were detected by ultrasonography
using 40 resected specimens. Seventeen of these 25 lesions (68 percent) were
histologically confirmed to be metastatic lymph nodes. One of 25 (4 percent) was
found to be lymphadenitis with no metastasis. Among the 25 lesions, 5 (20
percent) were histologically confirmed to be tumor deposits, 2 (8 percent) fatty
tissue, and 22 (88 percent) carcinoma. CONCLUSIONS: Low echoic lesions were
histologically confirmed to be tumor deposits (20 percent) and metastatic lymph
nodes (68 percent). Although these data show deficiencies and limitations of the
accuracy of endorectal ultrasonography, they compare favorably with other series,
and no other current technology can show similar accuracy.
PMID- 9645746
TI - Incidence of DNA replication errors in patients with multiple primary cancers.
AB - PURPOSE: Multiple primary cancers are a feature of hereditary nonpolyposis
colorectal cancer in which defects in DNA repair mechanisms result in
accumulation of replication errors within tumor DNA. We assessed replication
error incidence in multiple primary cancer patients who may have similar genetic
defects. METHODS: DNA was obtained from 69 patients from the Yorkshire region who
had developed colorectal cancer and one other primary tumor from the hereditary
nonpolyposis colorectal cancer tumor spectrum (28 colorectal, 12 stomach, 15
ovary, and 14 uterus). DNA was also obtained from 86 sporadic, single primary
cancer patients attending a colorectal cancer clinic. Replication error status
was assessed at five microsatellite loci using fluorescent polymerase chain
reaction and computer-assisted analysis. RESULTS: The replication error phenotype
was observed in 7 of 86 (8 percent) of the sporadic single primary patients. This
compared with 23 of 69 (33 percent) of the multiple primary group (P < 0.001).
Replication error was also observed more frequently in each subgroup. Even
excluding patients from families meeting the Amsterdam criteria (likely to be
hereditary nonpolyposis colorectal cancer and have the replication error
phenotype), this increased frequency remained in both the multiple primary group
(P < 0.005) and multiple colorectal and colorectal/uterine subgroups (P < 0.001).
CONCLUSIONS: Results suggest that genetic instability plays an important role in
development of multiple primary cancers, particularly from certain cancer
subsets. Testing for replication errors may be an appropriate way of identifying
individuals at risk of multiple primary cancers.
PMID- 9645747
TI - Relationship between serum ELAM-1 and metastasis among patients with colon
cancer.
AB - PURPOSE: We studied serum ELAM-1 levels in colon cancer patients. METHODS AND
RESULTS: Serum ELAM-1 levels were significantly higher in 52 patients with colon
cancer (mean +/- standard deviation, 69.3 +/- 28.6 U/ml) compared with 32 healthy
volunteers (36.5 +/- 11.9 U/ml; P < 0.001). The mean serum ELAM-1 level in
patients with metastatic tumors was significantly greater than that of patients
with nonmetastatic tumors. Sensitivity and specificity of serum ELAM-1 elevation
in detecting metastasis was 75 and 87.5 percent, respectively. Those of
carcinoembryonic antigen and carbohydrate antigen 19-9 elevations were 71.4 and
62.5 percent and 35.7 and 91.7 percent, respectively. Twenty-five (89.3 percent)
of 28 metastatic tumors showed either serum ELAM-1 or carcinoembryonic antigen
elevation. There were weak but significant correlations found between serum ELAM
1 and carcinoembryonic antigen or carbohydrate antigen 19-9 levels. Moreover,
serum ELAM-1 increased before detecting the recurrence by imaging in five of
seven recurrent colon cancer patients. CONCLUSION: These findings suggest that
serum ELAM-1 could be a useful tumor marker for colon cancer, especially in
synchronous and metaclonous metastasis.
PMID- 9645748
TI - Management of pilonidal sinus with the Limberg flap.
AB - PURPOSE: The aim of this study was to demonstrate the advantages of rhombic
excision and Limberg flap closure in the treatment of pilonidal sinus disease.
METHODS: We treated 24 patients who had chronic pilonidal sinus disease with
rhomboid excision and Limberg flap closure. RESULTS: All patients were followed
up for a period of 27 months. Mean hospital stay was 4.1 days, and mean time
until return to work was 17.5 days. There was no surgical wound infection.
Complication rate was 12.5 percent. During the follow-up period, no recurrence
was found. CONCLUSION: Because other treatment methods carry a significant
failure rate, this technique is an effective alternative in the treatment of
pilonidal sinus disease.
PMID- 9645750
TI - Rectal sleeve advancement: repair of rectovaginal fistula associated with
anorectal stricture in Crohn's disease.
AB - Successful repair of rectovaginal fistula in patients with Crohn's disease has
been reported when these patients have a normal appearing rectum. We report the
performance of stricturectomy in conjunction with circumferential rectal sleeve
advancement for patients who have a rectovaginal fistula arising from an
anorectal stricture secondary to Crohn's disease. This technique provides for
repair of rectovaginal fistula and correction of the anal stricture and maintains
continence.
PMID- 9645749
TI - Pelvic floor function in patients with clinically complete spinal cord injury and
its relation to constipation.
AB - PURPOSE: Constipation is a common problem in patients with spinal cord injury.
The aim of this study is to analyze the role of pelvic floor dysfunction in the
development of constipation. METHODS: Twenty-five patients with clinically
complete supraconal spinal cord injury were studied by means of colonic transit
time, anal manometry, electrophysiologic testing, and sensory-evoked potentials.
RESULTS: Sixteen patients had prolonged total and segmental colonic transit times
(Group C), and nine patients had normal colonic transit times (Group NC). Basal
pressure and anal pressure during coughing, Valsalva's maneuver, and rectal
distention were diminished in all patients, but no differences were observed
between Group C and Group NC. Rectal sensation was preserved in eight patients,
but this was not related to the absence of constipation. In seven of these eight
patients, somatosensory-evoked potentials could be recorded, which indicated an
incomplete cord lesion. Synergic relaxation of the pelvic floor during straining
was never observed; dyssynergia was seen in ten (7 in Group C and 3 in Group NC;
P = not significant) patients. Associated peripheral nerve damage was present in
40 percent of patients but did not predispose these patients to constipation.
CONCLUSIONS: Loss of rectal sensation, dyssynergic pelvic floor contraction
during straining, associated peripheral nerve damage, and insufficient rise of
intraabdominal pressure could not be held responsible for constipation as a
result of spinal cord injury. A prolongation of the colonic transit time is the
most important mechanism, and therapy should be directed toward it.
PMID- 9645751
TI - Double-gracilis anorectal neosphincter: technique of reconstruction after
necrosis of the distal part of the muscles.
AB - PURPOSE: The aim of the present study is to demonstrate further reconstruction of
a double-gracilis anorectal neosphincter that had been destroyed because of a
severe postoperative perineal infection, with necrosis of the distal part of the
muscles. METHOD: Each residual gracilis muscle was split longitudinally into two
branches, which surrounded the neorectum, one posteriorly and the other one
anteriorly, so as to perform a perineorectal double sling. RESULT: Owing to a
poor functional result, continence was achieved only by the support of an
implantable pulse generator. CONCLUSION: This technique seemed to permit the
optimum use of the contractile potential of the residual gracilis muscles, which
did not show evidence of defunction-related or ischemia-related fibrosis.
PMID- 9645752
TI - Passage of a large bowel cast caused by acute ischemia: report of two cases.
AB - PURPOSE: We report two cases of spontaneous anal passage of a large bowel 'cast'
caused by acute ischemic injury. METHODS: Clinical, laboratory, endoscopic, and
pathologic features were reviewed, and the literature was searched for similar
cases. RESULTS: An 85-year-old male who had undergone aortic surgery recovered
from rectosigmoid ischemia after undergoing a descending colostomy. A 74-year-old
male with severe pancreatitis developed a postischemic sigmoid stricture but did
not have operative treatment before death of pneumonia three months after the
episode. A literature review revealed six cases of passage of a large bowel cast.
In the eight total patients, infarcted muscularis propria was found in seven
specimens, five patients had a diversion procedure, and seven survived.
CONCLUSION: Passage of a large bowel cast is an extraordinary complication of
ischemia that often requires diverting surgery, and most patients survive the
ischemic injury.
PMID- 9645753
TI - A father and son with Turcot's syndrome: evidence for autosomal dominant
inheritance: report of two cases.
AB - Typical Turcot's syndrome is characterized by the association of a brain glioma
together with multiple colonic polyposis, in which the number of polypoid lesions
is small and the association of colonic cancer occurs at a younger age than in
familial adenomatous polyposis. We describe a family in which both the father and
his son presented with typical Turcot's syndrome without parental consanguinity.
This is the first report of a family that is considered to follow an autosomal
dominant inheritance. After reviewing 25 documented cases in which the average
age of death was 20.3 years old, it was learned that the major cause of death was
brain tumor (76 percent) and the minor cause was colon cancer (16 percent).
Patients were very young and, therefore, unlikely to have produced a child before
their death. These facts seem to support the theory that Turcot's syndrome is an
autosomal dominant disorder.
PMID- 9645754
TI - Endosonographic image of a retrorectal bowel duplication: report of a case.
AB - PURPOSE: Endosonographic image and surgical therapy of a retrorectal bowel
duplication are described. METHODS, RESULTS, AND CONCLUSIONS: Compared with
standard investigations, the most accurate information about a retrorectal mass
in a 35-year-old woman could be obtained by means of endorectal ultrasound.
Guided by endorectal ultrasound, the mass was excised using a transanal
transrectal approach, and Kraske's operation could be avoided. Additionally,
histopathologic analysis of this rare disease is presented.
PMID- 9645755
TI - Induction of acute inflammation in vivo by staphylococcal superantigens I:
Leukocyte recruitment occurs independently of T lymphocytes and major
histocompatibility complex Class II molecules.
AB - Studies in our laboratory and others have recently shown that staphylococcal
enterotoxin-derived superantigens stimulate proinflammatory cytokine gene
expression in vitro. We have therefore investigated the ability of superantigens
to induce leukocyte accumulation at extravascular sites in vivo using the
subcutaneous air pouch model. Injection of staphylococcal enterotoxin A (SEA)
induced a significant accumulation of leukocytes over basal levels in a time- and
dose-dependent manner. It was also shown that superantigens are capable of
inducing this response in mice depleted of CD4 T cells, as well as in severe
combined immune-deficient and nude mice. These observations suggest that
superantigens are capable of inducing leukocyte accumulation independently of the
presence of T lymphocytes. Experiments were also conducted using mutant SEAs that
have a reduced binding affinity for major histocompatibility complex (MHC) Class
II molecules, as well as using MHC Class II-deficient mice. The results of these
experiments indicated that MHC Class II molecules are not required for the
observed effect of superantigens in vivo. Taken together, these results indicate,
first, that bacterial superantigens promote inflammation in subcutaneous tissue
in vivo and, second, the potential existence of a novel receptor for
superantigens that mediates this subcutaneous inflammatory response.
PMID- 9645756
TI - Development of porous defects in plasma membranes of adenosine triphosphate
depleted Madin-Darby canine kidney cells and its inhibition by glycine.
AB - Studies during the past decade have led to the recognition of a fundamental,
widely expressed mechanism of structural damage in energy-deprived cells, which
is suppressed by physiologic levels of glycine and is independent of Ca2+
availability or alterations of cytosolic free Ca2+. To gain insight into this
process, Madin-Darby canine kidney (MDCK) cells were depleted of adenosine
triphosphate (ATP) by a mitochondrial uncoupler in glucose-free medium, and
intracellular free Ca2+ was clamped at 100 nM to avoid calcium cytotoxicity.
Although the ATP-depleted cells swelled and blebbed and their plasma membranes
appeared to be under tension, they nevertheless became permeable to
macromolecules. The plasma membranes of these cells retained structural
continuity, as determined by morphologic observations, and confocal microscopy of
a plasma membrane protein label (Biotin: Ultra Avidin-Texas Red) and a lipid
label (NBD-sphingomyelin). Using fluoresceinated dextrans of graded molecular
size, membrane permselectivity was examined noninvasively by confocal microscopy.
Measured as inside/outside ratios of fluorescence intensity, the permeability
indices showed progressively greater restriction to diffusion of increasingly
larger dextran molecules across plasma membranes, with sharp break-points between
70,000 and 145,000 daltons (d). The results indicated that the membranes behaved
as if they were perforated by water-filled channels or "pores," with size
exclusion limits of molecular dimensions. The membrane defects evolved from small
pores permeable only to propidium iodide (668 d) and the smallest dextran (4,000
d), before enlarging with time to become permeable to larger dextrans. Inclusion
of glycine during ATP depletion did not affect cell swelling or blebbing but
completely prevented the development of permeability defects. Treatment of cells
before ATP depletion with a membrane-impermeant homobifunctional "nearest
neighbor" cross-linking agent, 3,3' dithiobis(sulfosuccinimidylpropionate),
suppressed the development of permeability defects, even in the absence of
glycine. These observations suggest that the cellular abnormality that is
suppressed by glycine involves rearrangement of plasma membrane proteins to form
water-filled pores large enough to leak macromolecules.
PMID- 9645757
TI - Status of deleted in colorectal cancer gene expression correlates with
neuroblastoma metastasis.
AB - Neuroblastoma is an embryonal tumor of neural crest origin noted for its
heterogeneity at the clinical, histologic, and molecular levels. The deleted in
colorectal cancer (DCC) protein is an adhesion family molecule of unequivocal
importance in neural development that has also been implicated in several
malignancies, including neuroblastoma, through its apparent loss of function.
Immunohistochemical assessment of the DCC protein was performed on a group of 49
neuroblastoma specimens and examined in relation to important clinical,
histologic, and molecular parameters. DCC expression was significantly associated
with neuroblastoma dissemination as primary tumors from Stage 1 to 3 patients
(15/20, 75%) more frequently exhibited the DCC protein than those from Stage 4
patients (5/13, 38%; p = 0.0415). Primary tumors were more frequently DCC
positive (20/33, 61%) as compared with metastatic deposits (3/16, 19%; p =
0.0063), and a single case of a paired primary and metastatic deposit
demonstrated the apparent loss of DCC gene expression with tumor progression. The
remaining five paired specimens were DCC-negative in both the primary tumor and
metastatic deposit. No significant association was appreciated between DCC
expression and patient age, the Shimada histologic classification, or N-Myc
amplification. These results provide evidence that DCC expression may be lost in
the course of metastatic spread in a subset of neuroblastomas. Moreover, DCC
function is implicated in neuroblastoma dissemination in a manner independent of
N-Myc.
PMID- 9645758
TI - Oligoclonal T-cell proliferation and interferon-gamma production in
periprosthetic inflammation.
AB - Total joint arthroplasty has dramatically changed the treatment options for
patients with destructive joint disease. The materials used to manufacture
implants are regarded as biologically inert; accordingly, arthroplasty is a very
successful intervention for most patients. However, a subset of patients develops
an inflammatory reaction around the prosthesis, causing implant loosening and
irreversible bone destruction. To identify mechanisms leading to periprosthetic
inflammation, the function and composition of macrophages and T cells accumulated
in the pseudosynovia were examined. Tissue-infiltrating macrophages synthesized a
spectrum of proinflammatory cytokines including IL-1beta, IL-6, and TGF-beta. T
cells recruited to the periprosthetic inflammatory lesions were characterized by
restricted diversity of T-cell receptors and the emergence of dominant clonal
populations. T cells with identical T-cell receptor sequences, and thus with
identical antigen specificity, were isolated from anatomically distinct and
independent regions of the tissue. Transcription of IL-2, IFN-gamma, and, in some
patients, IL-4 genes in the periprosthetic membrane indicated functional
activation of infiltrating T cells. Correlation of periprosthetic osteolysis with
the tissue cytokine pattern demonstrated a relationship between IFN-gamma
transcription and bone loss. We propose that antigen-recognition events are
critically involved in the development of periprosthetic inflammation and that
the functional commitment of T cells recruited to the periprosthetic region
influences whether periprosthetic inflammation is complicated by bone
destruction.
PMID- 9645759
TI - Localization of matrix metalloproteinases-1, -2, and -9 and tissue inhibitor of
metalloproteinase-2 in interstitial lung diseases.
AB - In interstitial lung diseases, deposition of extracellular matrix (ECM) in
alveoli and degradation of ECM lead to pulmonary structural remodeling. The
changes in ECM and the localization of matrix metalloproteinases (MMPs) and a
tissue inhibitor of metalloproteinases (TIMP) in the lung tissues of patients
with bronchiolitis obliterans organizing pneumonia (BOOP) and idiopathic
pulmonary fibrosis (IPF) were investigated. Immunohistochemical analysis for the
detection of fibronectin, collagen-I, -III, and -IV, smooth muscle actin, MMP-1
(interstitial collagenase), -2 (gelatinase A), and -9 (gelatinase B), and TIMP-2,
and in situ hybridization for the detection of MMP-9 mRNA were performed. Western
blotting of lung tissue homogenates was performed for MMP-2 and MMP-9. The
gelatinolytic activities of the homogenates were also determined using gelatin
zymography. Fibronectin and collagen-I, -III, and -IV were detected in the intra
alveolar fibrosis in addition to the interstitium of these diseases. MMP-1, MMP
2, MMP-9, and TIMP-2 were detected in the regenerated epithelial cells covering
intra-alveolar fibrosis. Myofibroblasts in intra-alveolar fibrosis in BOOP showed
predominant reaction for MMPs, and they ultrastructurally appeared to be
phagocytosing collagen fibrils, and those of IPF showed a predominant reaction
for TIMP-2. New vascularization in intra-alveolar fibrosis was exclusively
observed in cases of BOOP, and the endothelial cells were positive for MMP-2.
Western blotting showed the existence of a latent form of MMP-9 and latent and
active forms of MMP-2, and gelatin zymography revealed that the ratio of
active/latent forms of MMP-2 in BOOP is significantly larger than that in the
control lungs. Predominant MMPs in BOOP may constitute the mechanism of
reversibility of fibrotic changes in this disease. TIMP-2 in myofibroblasts in
IPF may contribute to the stable ECM deposition and the irreversible pulmonary
structural remodeling.
PMID- 9645760
TI - Expression of the 150-kd oxygen-regulated protein in human breast cancer.
AB - Tumor cells subjected to environmental stress, such as oxygen deprivation
followed by reoxygenation, redirect biosynthetic pathways to express oxygen
regulated proteins (ORPs) and heat-shock proteins (HSPs). The 150-kd oxygen
regulated protein (ORP150) is a novel endoplasmic reticulum-associated
polypeptide in the HSP70 family. In view of links between expression of HSPs/ORPs
and tumor properties, especially tumor invasiveness and resistance to therapeutic
regimens, expression of ORP150 in human breast cancers was examined. Western and
Northern blotting demonstrated elevated expression of ORP150 in breast cancer,
regardless of estrogen receptor status, compared with normal breast tissue.
Immunohistochemical and in situ hybridization techniques revealed that
infiltrating cancer cells in the stroma expressed ORP150 more strongly than large
nests of cancer cells. Furthermore, pancreatic and thyroid carcinomas also
displayed greater ORP150 expression. These results suggest that ORP150 is up
regulated in tumors and, in breast tumors, may be associated with tumor
invasiveness.
PMID- 9645761
TI - Chemotherapy of an experimental Trypanosoma cruzi infection with specific
immunoglobulin-chlorambucil conjugate.
AB - Hybrid molecules were constructed with either polyclonal antibodies against
Trypanosoma cruzi antigens or monoclonal antibody against Trypanosoma brucei
brucei low-density lipoprotein (LDL)-receptor conjugated with chlorambucil.
Physical-chemical analysis of the hybrid molecule showed four chlorambucil
coupling sites in each IgG and a binding constant in the order of 10(4).
Maintenance of IgG integrity was indicated by its circular dichroism pattern.
Biologic activity of the hybrid molecule was shown by its inhibitory effect on
the mobility and proliferation of the parasite. An IgG-chlorambucil conjugate,
produced with monoclonal antibody anti-T. b. brucei LDL-receptor, led to the
immobilization of the T. cruzi forms, albeit at a much lesser level than that
obtained with a mouse polyclonal anti-T. cruzi IgG linked to the drug. Targeting
experimental T. cruzi infection with a specific IgG-chlorambucil conjugate
resulted in consistent reduction of parasitemia and mortality, thus showing its
potential usefulness in controlling the acute form of the disease.
PMID- 9645762
TI - Detection of transcripts initiated from two viral promoters (Cp and Wp) in
Epstein-Barr virus-infected nasopharyngeal carcinoma cells and biopsies.
AB - Different activation of Epstein-Barr virus (EBV) promoters results in distinct
expression patterns of EBV nuclear antigens (EBNAs) and may further decide the
role of EBV in the cellular pathogenesis. In EBV-associated nasopharyngeal
carcinoma (NPC) biopsies, it has generally been believed that Q promoter (Qp)
initiated EBNA1 is the only EBNA gene to be expressed and that the other two
viral promoters, Cp and Wp, which can lead to expression of EBNA1-6, are
inactive. However, the failure to demonstrate the activities of Cp and Wp may
have been due to the limited sensitivities of detection approaches used. In the
present article, the EBV promoter usage and gene expression were re-examined in
both EBV-infected NPC cells in vitro and NPC biopsies in vivo. An NPC cell line
susceptible to EBV infection in vitro was established by transfection with a
plasmid expressing a well-known EBV receptor, CR2. The presence of viral DNA and
EBNA proteins was demonstrated in these EBV-infected cells using PCR and
anticomplement immunofluorescence assay, respectively. As has been identified in
NPC biopsies, viral transcripts of Qp-initiated EBNA1, latent membrane protein
(LMP)1, LMP2A, LMP2B, and BamHI A genes, as well as the EBV-encoded small RNA
(EBER)1 were detected in these in vitro-infected cells using reverse
transcription-PCR. Notably, viral transcripts initiated from Cp or Wp were also
found in the infected cells. Furthermore, Cp- or Wp-initiated transcripts and
EBNA2 mRNA were detected in some NPC biopsies. Taking advantage of this sensitive
detection approach, our observation that Cp and Wp may be active in NPC cells
raises the possibility that EBNA2 to 6, in addition to EBNA1, may play roles in
the pathogenesis of NPC.
PMID- 9645763
TI - Mutation of the p53 gene in postradiation sarcoma.
AB - Radiotherapy is known to cause secondary malignancies in the radiation field;
postradiation sarcomas (PRS) are one example of such malignancies. Little is
known about the genetic changes, including p53 gene alterations, that are thought
to play a role in the tumorigenesis of human PRS. In the present study, p53 gene
mutations were analyzed on paraffin-embedded specimens from 24 patients with PRS
(4 men and 20 women) by polymerase chain reaction-single-strand conformation
polymorphism (PCR-SSCP) followed by direct sequencing. The primary tumors of
these patients were uterine cervical cancers in 14, breast cancers in 3,
malignant lymphomas in 2, and others in 5. Total radiation doses ranged from 36
to 300 Gy (median, 60 Gy). The latent period between completion of radiation
therapy and development of PRS ranged from 3 to 34 years (median, 10 years).
Malignant fibrous histiocytoma was the most common PRS, accounting for 12 cases.
PCR-SSCP revealed the aberrant mobility shifts of bands in 24 cases: 21 shifts in
exon 5, 18 in exon 7, and 12 in exon 8. Direct sequencing of the SSCP product
revealed a total of 58 mutations in 21 (88%) of 24 cases: 4 cases had a single
mutation, 5 had 2 mutations, 5 had 3 mutations, 6 had 4 mutations, and 1 had 5
mutations. Although 31% of the mutations did not change an amino acid, every
tumor had at least one mutation that did, which may have provided the selection
pressure for expansion. The frequency of p53 gene mutation in sporadic soft
tissue sarcomas was 20%. These findings highlighted the extraordinarily high
frequency of p53 gene mutations in PRS. G:C to A:T transition at dipyrimidine
sites was found in 14 (58%) of 24 cases. Collectively, these findings indicate
that radiation is causative for soft tissue sarcomas via p53 gene mutations.
PMID- 9645764
TI - The membrane-type-matrix metalloproteinase/matrix metalloproteinase-2/tissue
inhibitor of metalloproteinase-2 system in periprosthetic connective-tissue
remodeling in loose total-hip prostheses.
AB - The aim of the present study was to investigate the proteolytic potential and
localization of matrix metalloproteinase (MMP)-2 in relation to its regulatory
protein, membrane-type-MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2
(TIMP-2), as well as to clarify an important step in the cascade of
periprosthetic connective-tissue remodeling in loose total-hip prostheses.
Immunohistochemical analysis revealed increased expression of MT1-MMP, MMP-2, and
TIMP-2 in fibroblasts, synovial lining-like cells, and endothelial cells, as well
as, to some extent, in monocyte/macrophage-like cells in both tissues from the
bone-implant interface and reactive cellular tissues from regenerating capsules
in loose hip joints, when compared with control fibrous tissues between bone and
implants retrieved from unloosened hip joints. In loose hip joints, reverse
transcription-PCR analysis showed the presence of MT1-MMP, MMP-2, and TIMP-2 mRNA
in both the bone-implant interface and regenerating capsular tissues. Increased
protein levels of MMP-2 and TIMP-2 were also demonstrated by an ELISA, and those
of MT1-MMP were shown by immunoblot analysis. Gelatin-zymographic analysis
confirmed the presence of both pro- and active forms of MMP-2, which suggested
the in situ activation of MMP-2 by MT1-MMP in the loose hip joints. Collectively,
these data suggest that the MT1-MMP/MMP-2/TIMP-2 system participates in the
extracellular matrix degradation and periprosthetic connective-tissue remodeling
in loose hip joints, and may thus contribute to the periprosthetic weakening,
loosening, and osteolysis that can occur around implants.
PMID- 9645765
TI - Abnormal thymocyte development and generation of autoreactive T cells in mixed
and cortical thymomas.
AB - To gain insight into the pathogenesis of thymoma-associated myasthenia gravis,
thymocyte maturation was investigated in mixed and cortical thymomas by three
color flow cytometry. Although we detected cells at all recognizable stages, we
noted an unusual increased percentage of early CD4+/CD3- thymocytes--especially
in mixed thymoma--and a pronounced decreased percentage of mature CD4+/CD3+ cells
in cortical thymomas as well. The percentage of CD3+/CD69+ cells that arose after
positive selection was reduced in both thymoma subtypes compared with control
thymuses, which suggests differences in the rate or efficiency of positive
selection particularly in mixed thymomas. Mature T cells in 10 of 11 thymomas
were not activated in situ as shown by the absence of CD25 expression. After
stimulation with recombinant human acetylcholine receptor alpha-subunit
fragments, thymocytes from 8 of 11 thymomas of both subtypes proliferated more
strongly than those from controls, regardless of whether the donors were
myasthenic. Responses of residual thymus cells to tetanus toxoid correlated well
with those of autologous blood T cells, whereas those from the thymomas clearly
did not--implying minimal colonization of thymomas by mature recirculating T
cells. In conclusion, our results show that cortical and mixed thymomas exhibited
differences in thymocyte maturation. Nevertheless, both thymoma subtypes seem to
contribute to the pathogenesis of paraneoplastic myasthenia gravis by generating
naive but potentially autoaggressive T cells; in some thymomas, these cells may
then be actively immunized inside the tumor.
PMID- 9645766
TI - Interleukin-8 production by polymorphonuclear neutrophils in patients with
rapidly progressive periodontitis: an amplifying loop of polymorphonuclear
neutrophil activation.
AB - Polymorphonuclear neutrophils (PMN) are the most abundant immune cells in
inflammatory gingival sites of patients with early onset periodontitis, localized
juvenile periodontitis, and rapidly progressive periodontitis (RPP). In the
latter, the large number of PMN in connective tissue may explain the marked
gingival destruction. Because interleukin-8 (IL-8) is a potent PMN
chemoattractant, we evaluated circulating levels and gingival mRNA expression of
IL-8. We found high IL-8 plasma levels as well as strong IL-8 mRNA expression in
both epithelial and connective gingival cells from patients with RPP. Moreover,
the gingival PMN themselves contained IL-8 mRNA, suggesting an autoamplification
of PMN recruitment and activation in the gingiva. We also measured the expression
of adhesion molecules at the PMN surface as well as the oxidative burst in whole
blood from 14 patients with RPP, using flow cytometry to avoid irrelevant
stimulations and to analyze single cells. In RPP patients, resting PMN showed
reduced L-selectin, Lewis x, and sialyl Lewis x antigen expression as well as
increased H2O2 production. These modifications of PMN adhesion molecule
expression, together with their increased basal oxidative burst and excessive IL
8 production, may contribute to the noxious inflammatory reaction, which may in
turn be autopotentiated by PMN production of IL-8. In addition, PMN showed a lack
of increased response (H2O2 production) to formyl peptides after ex vivo priming
with IL-8, possibly owing to IL-8 desensitization that may be involved in the
increased susceptibility of RPP patients to infection. After appropriate
treatment of RPP, the reduction in inflammation was associated with a return to
control levels of both plasma IL-8 and PMN functions, suggesting that these
features are linked.
PMID- 9645767
TI - Direct detection of premature protease activation in living pancreatic acinar
cells.
PMID- 9645768
TI - Development, progression, and androgen-dependence of prostate tumors in probasin
large T antigen transgenic mice: a model for prostate cancer.
AB - Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and
androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was
linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that
removes the expression of the small t antigen) to deliver consistently high
levels of transgene expression to the transgenic mouse prostate. Seven male
founders, their male offspring, and all the male offspring from two female
founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of
age, indicating that the incidence of transformation was 100%. Tumorigenesis in
the LPB-Tag animals progressed in a manner similar to that observed in the human
prostate. Initially, multifocal proliferating lesions were detected in the
prostatic epithelium, which continued to progress into hyperplasia involving the
entire epithelium and then low-grade dysplasia. Reactive stromal proliferation
was induced and continued to develop throughout the progression to high-grade
dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies
indicated that most stromal cells stained positively for both androgen receptor
and smooth muscle alpha-actin, suggesting that stromal overgrowth largely
represented mesenchymal cells that had differentiated into smooth muscle cells.
Epithelial cell transformation was accompanied by the down-regulation of
differentiated function, as suggested by the loss of dorsolateral prostate
specific secretory proteins. Tumor growth was regarded as androgen-dependent
because tumors regressed in animals castrated at 11 weeks of age, and androgen
treatment restored both epithelial/stromal cell ratio and tumor growth.
Furthermore, small populations of prostatic epithelial cells in castrated animals
continued to proliferate, suggesting the potential for androgen-independent
growth. Although prostatic metastasis to other organs was not observed, local
invasion was detected. In summary, the LPB-Tag animal model is unique in that it
is the only model generated with the Tag alone, thereby eliminating any
influences of the small t antigen on prostate tumor formation. Moreover, this
model undergoes molecular changes similar to those found in human prostate
including: (a) the multi-focal nature of tumorigenesis, (b) the progressive
histopathologic changes from low- to high-grade dysplasia similar to human
prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal
proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus,
the LPB-Tag prostate tumor model will be useful for studying the sequential
mechanisms underlying the development of multistep tumorigenesis.
PMID- 9645769
TI - Superior survival of young women with malignant melanoma.
AB - BACKGROUND: The Commission on Cancer data from the National Cancer Data Base
(NCDB) relating to patients with malignant melanoma are used to examine patterns
of long-term survival by patient gender and age, stage of disease, disease
morphology, and anatomic subsite. METHODS: Five calls for data have yielded more
than 3,700,000 cases of cancer for the years 1985 through 1993, including 23,341
cases of malignant melanoma between 1985 and 1989, from hospital cancer
registries across the US, representing slightly less than a quarter of all
melanoma cases diagnosed in the US between 1985 and 1989. RESULTS: Three
statements can be made from this data: (1) There is little difference in the
frequency of malignant melanoma between men and women with respect to stage of
disease or morphology. However, differences between the genders do appear with
respect to the anatomic subsite of melanotic tumors. (2) Overall, young women (45
years of age and under) enjoy superior survival rates when compared with older
women (55 years of age and older) and men of any age. (3) The survival advantage
held by young women is particularly pronounced among patients diagnosed with
advanced stage disease. CONCLUSIONS: These data suggest that factors present in
younger women may be critical in the superior survival rates seen among
premenopausal women and might be hormonal in nature.
PMID- 9645770
TI - A single institution's experience with transperitoneal laparoscopic hernia
repair.
AB - BACKGROUND: Previous evaluations of endoscopic hernia surgery mostly are based on
small prospectively documented series or on a few randomized comparative studies.
In the following, results of a large single-institution experience concerning the
transabdominal preperitoneal patch (TAPP) technique with regard to the
development of methods and the routine use are described. METHODS: From April
1993 to March 1997, 2,700 TAPP procedures were performed at the Department of
General and Visceral Surgery, Marien-hospital, Stuttgart, Germany. The follow-up
was documented prospectively in all cases by use of computed data base. RESULTS:
The majority of patients (83.8%) were operated because of primary hernias. In
17.2% a first or multiple recurrence of an inguinal hernia was indicated. At a
median postoperative observation period of presently 20 months and a follow-up
rate of 86.5%, 28 recurrences have been determined so far (total recurrence rate
1.03%), 6 of which occurred after a recurrent hernia reparation (1.33%) and 22
after primary hernia repair (0.97%). The most common cause for recurrence was in
39.3% a mesh (12 x 8 cm) being too small. The total complication rate was 4.6%;
as an expression of the learning curve it was reduced from 7.8% (operations 1 to
500) to 2.8% (operations 2,200 to 2,700). CONCLUSIONS: According to our
experience, the TAPP technique is sufficiently applicable as a standard method
for an unselected group of patients in a routine setting. It is especially suited
to the repair of recurrent and bilateral hernias as well as for patients with a
high risk for recurrence that can profit from a tension-free endoscopic
procedure, particularly in case of obesity.
PMID- 9645771
TI - Intrahepatic biliary enteric bypass provides effective palliation in selected
patients with malignant obstruction at the hepatic duct confluence.
AB - BACKGROUND: Palliating the effects of biliary obstruction is a major goal of
therapy in patients with cancer at the hepatic duct confluence. This study was
undertaken to evaluate the effectiveness of intrahepatic biliary-enteric bypass
to either the segment III duct or the right sectoral hepatic ducts in patients
with unresectable hilar cholangiocarcinoma or gallbladder carcinoma. METHODS:
From December 1991 to October 1996, 55 consecutive bypass procedures were
prospectively evaluated in patients with unresectable hilar cholangiocarcinoma or
gallbladder cancer. Patients were divided into three groups based on the primary
tumor and the type of bypass performed: group 1A, cholangiocarcinoma/segment III
bypass (n = 20); group 1B, cholangiocarcinoma/right sectoral hepatic duct bypass
(n = 14); group 2, gallbladder cancer/segment III bypass (n = 21). RESULTS: Mean
hospital stay (14+/-2 days) and mean blood loss (629+/-84 mL) were similar among
the three groups. Perioperative death occurred in 6 patients (11%): 0 in group
1A, 3 each in groups 1B and 2. All survivors had relief of jaundice and pruritus
after bypass. Complications occurred in 25 patients (45%). Preoperative
transhepatic biliary drainage, performed in 14 patients prior to referral, was
associated with a higher incidence of contaminated bile, greater operative blood
loss, and postoperative biliary leak that was less likely to resolve
spontaneously. Median survival in patients with cholangiocarcinoma (groups 1A and
1B) was 52 weeks and was unaffected by the type of bypass performed. By contrast,
median survival in patients with gallbladder cancer (group 3) was 20 weeks; all
but 3 died within 32 weeks of surgery. In patients with cholangiocarcinoma, the 1
year bypass patency was 80% in group 1A (segment III bypass) and 60% in group 1B
(right sectoral hepatic duct bypass). Overall, there were 9 late bypass failures
(18%) requiring reintervention. CONCLUSIONS: Intrahepatic biliary-enteric bypass
effectively relieves symptoms due to malignant hilar obstruction. In patients
with cholangiocarcinoma, segment III bypass provides excellent palliation with
relatively few late complications and can be performed with minimal morbidity and
mortality. Bypass to the right sectoral hepatic ducts, on the other hand, is
associated with significant procedure-related morbidity and mortality and more
late complications. Patients with gallbladder cancer, because of their poor
survival, are probably better palliated by percutaneous biliary stenting.
PMID- 9645772
TI - Use of preoperative autologous blood donation in liver resections for colorectal
metastases.
AB - BACKGROUND: Transfusion of allogeneic blood is associated with risks of human
immunodeficiency virus and hepatitis transmission, transfusion reactions, and
other potential immunologic and infectious complications. To determine if
predonation of autologous blood impacts upon transfusion practice and clinical
outcome following liver resection, clinical records of 379 consecutive patients
undergoing hepatic resection for metastases of colorectal cancer were identified
from the prospective hepatobiliary database and reviewed. METHODS: Of the 379
hepatic resections performed for colorectal metastases between January 1991 and
January 1996, 240 (63%) were hepatic lobectomy or trisegmentectomy. Thirty-two
percent of patients (123 of 379) agreed to preoperative blood donation (POBD),
and their clinical characteristics including age, preoperative hemoglobin, and
operative mortality were comparable with those of patients without POBD. Liver
resections were carried out using standard vascular inflow and outflow control.
Parenchymal transections were performed bluntly with maintenance of low central
venous pressure (0 to 5 cm H2O). No vascular isolation or normovolemic
hemodilution was used intraoperatively. All erythrocyte transfusions during the
entire hospital stay were considered and compared between the two groups.
RESULTS: Forty-five percent of patients (172 of 379) received blood transfusions
during or after liver resections, of which 61% (105 of 172) required only 1 or 2
units. Only 17% of the POBD group required allogeneic blood. This was
significantly less than the group without POBD (43%, P <0.01). There was no
significant difference in the operative mortality (2.3% versus 4.9%, P = 0.2) and
the median survival (50 versus 40 months, P = 0.3). CONCLUSIONS: Major hepatic
resections using current surgical techniques can be performed safely with low
blood loss and transfusion is required for only a minority of patients. POBD
further reduces transfusion requirement.
PMID- 9645773
TI - Management of true aneurysms of the splenic artery.
AB - BACKGROUND: Splenic artery aneurysms (SAA) are detected with increasing frequency
but their management still remains controversial. This paper relates our
experience in the outcome and management of ruptured aneurysms of the splenic
artery. METHODS: Between 1977 and 1996, 8 patients presented to our institution
with a ruptured SAA. Their ages ranged from 25 to 72 years (mean 55 ys). RESULTS:
All patients presented with rupture as the first sign of SAA. One patient was at
32 weeks of gestation and rupture suggested placental abruption. Three patients
required cardiopulmonary reanimation prior to surgical procedures.
Splenopancreatectomy (n = 4), splenectomy (n = 2), and ligation of the splenic
artery (n = 1) were performed. Seven of the 8 patients survived. Size of
aneurysms ranged from 2 cm to 3.5 cm (mean 3 cm). CONCLUSIONS: SAA may rupture at
any age. Diagnosis during pregnancy rests upon a high index of suspicion. The
mortality rate remains low if immediate resuscitation is performed and an
aggressive surgical approach is taken.
PMID- 9645775
TI - Interpretation of postvagotomy endoscopic Congo red test results in relation to
ulcer recurrence 5 to 12 years after operation.
AB - BACKGROUND: The aim of the present study was to estimate, after vagotomy, the
location and extension of residual vagal innervation of the gastric corpus mucosa
by using the endoscopic Congo red test (ECRT) and its relation to recurrent ulcer
(RU), as well as the results of quantitative gastric acid tests: basal acid
output (BAO), maximal acid output (MAO), and nocturnal acid output (NAO).
METHODS: A total of 271 consecutive vagotomized duodenal ulcer (DU) patients were
studied 5 to 12 years (mean 8 years) after the operation. In all cases
gastroscopy and ECRT were performed simultaneously. ECRT was considered positive
if a red to black-blue (pH <3.0) color change of the gastric corpus mucosa
occurred within the first 3 minutes, and the cases were classified as having
small extension (SE), ie, one or more areas with a diameter of 1 to 30 mm, or
large extension (LE), ie, 20% or more of the gastric corpus showing residual
vagal innervation. No red to black-blue changes (pH >3.0) were attributed to
negative ECRT. BAO, MAO, and NAO were determined preoperatively and
postoperatively in 108 cases out of 271 and correspond with ECRT results.
RESULTS: Recurrent ulcer occurred in 18 out of 135 ECRT-positive and in 1 out of
136 ECRT-negative cases. RU occurred 5 times more frequently in LE than SE cases
(P <0.05). The postoperative mean values of BAO, MAO, and NAO were significantly
higher in ECRT-positive than in ECRT-negative cases (P <0.001), and higher in LE
than in SE cases (P <0.01; for NAO, P >0.05). CONCLUSION: ECRT is a practical and
reliable method in the evaluation of postvagotomy DU patients: Negative ECRT
practically includes recurrent ulcer risk; positive ECRT of large extension is
related to fivefold higher recurrent ulcer risk compared with ECRT of small
extension; and ECRT reflects BAO, MAO, and NAO results and can be used instead of
them as a less time-consuming procedure, which is more convenient for the
patient.
PMID- 9645774
TI - Transfusion of phosphoenolpyruvate-treated blood increases oxygen consumption in
acute hemorrhage.
AB - BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen
affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated
blood and conventionally stored blood on oxygen consumption in acutely anemic
dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1
hour they were transfused to a hematocrit of 18% with control or
phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin
P50 measurements allowed calculation of oxygen consumption during anemia, and
posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with
phosphoenolpyruvate-treated blood allowed greater O2 consumption than control
(8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or
venous PO2 or pH; there were marked differences in HOA, measured by
posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation.
CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected
to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen
consumption at a similar hematocrit when compared with untreated banked blood.
PMID- 9645776
TI - Intraoperative cytodiagnosis for detecting a minute invasion of the portal vein
during pancreatoduodenectomy for adenocarcinoma of the pancreatic head.
AB - During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we
frequently encountered cases in which the superior mesenteric-portal venous
confluence (SMPVC) was involved with cancer. With regard to the indication of the
concomitant SMPVC resection, as suggested by recent papers, a better long-term
outcome would be expected if the cancer invasions were limited to the tunica
adventitia or media of the SMPVC wall. Since this raised fears whether such a
small SMPVC invasion was always detectable by macroscopic inspection alone, we
have performed an intraoperative cytology on the touch smear of the exposed SMPVC
wall for 23 patients with pancreatic head cancer. All of their SMPVCs were
separated from the pancreatic head and appeared to be intact at a macroscopic
level. As a result of the cytologic examination, however, 7 patients (30%) were
newly diagnosed as having cancer cells on the SMPVC wall, and they received an
additional resection of the SMPVC. Postoperative histology indicated that cancer
invasion into the SMPVC wall was present in 6 of the 7 patients, and that the
cancer invasions were limited in the tunica adventitia in 5 patients and to the
tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC
resection, our intraoperative cytology on the touch smear of the SMPVC is worth
performing more actively on the macroscopically intact-looking SMPVC during
resection of pancreatic cancer.
PMID- 9645777
TI - Development of a model for training and evaluation of laparoscopic skills.
AB - BACKGROUND: Interest in the training and evaluation of laparoscopic skills is
extending beyond the realm of the operating room to the use of laparoscopic
simulators. The purpose of this study was to develop a series of structured tasks
to objectively measure laparoscopic skills. This model was then used to test for
the effects of level of training and practice on performance. METHODS: Forty-two
subjects (6 each of surgical residents PGY1 to PGY5, 6 surgeons who practice
laparoscopy and 6 who do not) were evaluated. Each subject viewed a 20-minute
introductory video, then was tested performing 7 laparoscopic tasks (peg
transfers, pattern cutting, clip and divide, endolooping, mesh placement and
fixation, suturing with intracorporeal or extracorporeal knots). Performance was
measured using a scoring system rewarding precision and speed. Each candidate
repeated all 7 tasks and was rescored. Data were analyzed by linear regression to
assess the relationship of performance with level of residency training for each
task, and by ANOVA with repeated measures to test for effects of level of
training, of repetition, and of the interaction between level of training and
repetition on overall performance. Student's t test was used to evaluate
differences between laparoscopic and nonlaparoscopic surgeons and between each of
these groups and the PGY 5 level of surgical residents. RESULTS: Significant
predictors of overall performance were (a) level of training (P = 0.002), (b)
repetition (P < 0.0001), and (c) interaction between level of training and
practice (P = 0.001). There was also a significant interaction between level of
training and the specific task on performance scores (P = 0.006). When each task
was evaluated individually for the 30 residents, 4 of the 7 tasks (tasks 1, 2, 6,
7) showed significant correlation between PGY level and score. A significant
difference in performance scores between laparoscopic and nonlaparoscopic
surgeons was seen for tasks 1, 2, and 6. CONCLUSIONS: A model was developed to
evaluate laparoscopic skills. Construct validity was demonstrated by measuring
significant improvement in performance with increasing residency training, and
with practice. Further validation will require correlation of performance in the
model with skill in vivo.
PMID- 9645778
TI - Posterior or laparoscopic approach for adrenalectomy.
AB - BACKGROUND: The pathologies and size of adrenal lesions removed through the open
posterior and laparoscopic routes share remarkable similarities. This study aims
at comparing the relative merits of these two approaches. METHODS: Patients with
adrenal tumors operated on by posterior approach (n = 56) and transabdominal
laparoscopic approach (n = 12) between January 1981 and May 1997 were
retrospectively reviewed. RESULTS: The two groups were comparable in terms of
age, and the position, size, and weight of the tumor. The operative time of
posterior adrenalectomy was significantly shorter than that of laparoscopic
adrenalectomy (median 120 minutes versus 160 minutes), whereas laparoscopic
adrenalectomy was associated with less parenteral analgesic requirement (median 0
mg versus 225 mg), a shorter hospital stay (median 3 days versus 5 days), and a
shorter duration off work (median 11 days versus 26 days). The estimated blood
loss was also significantly reduced in the laparoscopic group (median 50 mL
versus 150 mL). CONCLUSIONS: Laparoscopic adrenalectomy is replacing posterior
adrenalectomy to become the procedure of choice for the majority of patients
undergoing adrenalectomy.
PMID- 9645779
TI - Ultrasonically activated shears in thyroid surgery.
AB - BACKGROUND: Ultrasonically activated shears (UAS) have been documented to be both
safe and fast devices in laparoscopic surgery. We studied whether the use of UAS
would have some advantage in thyroid surgery. METHODS: Thyroidectomies, performed
by one senior endocrine surgeon between December 1996 and February 1997, were
retrospectively matched, with patients operated on by the same surgeon using the
conventional method. RESULTS: Six pairs of total thyroidectomies and one pair of
lobectomies could be matched. Mean operating time was 100 minutes for the
patients operated on with the UAS and 154 minutes for the patients operated on
with the conventional method. The mean operating time with the UAS was thus on
average 64.6% of the operation time with the conventional method, with a 95%
confidence interval from 50.1% to 83.5% (t = 4.00, 6 df, P = 0.007). CONCLUSIONS:
In this material the use of UAS reduced significantly operating time in
thyroidectomies.
PMID- 9645780
TI - Rapid arterial anastomosis with titanium clips.
AB - BACKGROUND: The obvious advantages of rapid arterial anastomoses have prompted
the continuing search for more rapid anastomotic techniques to complement the
standard sutured anastomosis. Nonpenetrating, arcuate-legged titanium vascular
closure staple (VCS) clips were initially developed for microvascular
anastomoses. The purpose of this study was to compare VCS clips with sutured
arterial end-to-end anastomosis in larger vessels. METHODS: In 6 pigs, transacted
iliac arteries were reanastomosed with VCS clips on one side and continuous 6-0
polypropylene suture on the other. RESULTS: The reconstruction time was 8.4+/-5.2
minutes for clip closure and 12.0+/-6.6 minutes for suture closure (P = 0.033).
All vessels were patent half an hour after completing the anastomoses with no
signs of early thrombosis. CONCLUSIONS: Arterial end-to-end anastomosis can be
performed more rapidly with VCS clips than continuous sutures, and are
potentially useful in situations where the clamp time of the vessel is critical.
PMID- 9645781
TI - Do our current assessments assure competency in clinical breast evaluation
skills?
AB - BACKGROUND: The focus of teaching for clinical breast evaluation has been the
technique of breast examination. This study questions the relationship between
breast examination technique and the ability to detect physical findings.
METHODS: This study examines the relationship between breast examination skills
of 66 graduating primary care physicians as measured during an objective
structured clinical examination (OSCE) and lump detection sensitivity and
specificity on breast models. RESULTS: Overall breast examination performance
revealed 50% of maneuvers performed correctly. Mean breast model sensitivity for
lump detection was 40% and the mean breast model specificity was 77%. While a
mild correlation existed between breast examination skills and lump detection
sensitivity (r = .34, P = 0.01), no relationship was found between lump detection
specificity and examination skills. CONCLUSIONS: There is a limited relationship
between correct performance of breast examination maneuvers and the ability to
detect a breast lump when present. Breast examination skills and palpation skills
to detect masses may represent independently acquired skills with need for
separate instructional methodology. These results raise serious concerns about
the reliance on standardized patients alone for training in physical examination
skills.
PMID- 9645782
TI - Unstructured cases in case-based learning benefit students with primary care
career preferences.
AB - BACKGROUND: The impact of instructional method on students with opposing surgical
career orientations was investigated in a prospective study. METHODS: Students
were randomly assigned to structured or unstructured case-based discussions.
Clinical reasoning (OSCE and a diagnosis exercise), subject knowledge (multiple
choice test [MCT]), method preference, and pre-third year career preference were
compared. RESULTS: Twenty-two students listed a surgical career high (Surgical)
and 20 low (Primary). Surgical MCT scores were higher than Primary regardless of
instructional method. Surgical diagnosis exercise scores were higher than Primary
with the structured method (22.0+/-2.3 versus 15.1+/-3.0, P <0.08). Unstructured
scores on this exercise were similar (19.7+/-1.8 Surgical versus 20.3+/-3.5
Primary). Analysis of variance suggested an interaction on the diagnosis exercise
between method and career (P = 0.16). Students preferred the unstructured method.
CONCLUSIONS: The improved diagnosis exercise performance implies that
unstructured cases positively influence surgical domain specific reasoning for
nonsurgical career students. These method effects increase our understanding of
case-based methods in surgical education.
PMID- 9645783
TI - Computer-assisted learning versus a lecture and feedback seminar for teaching a
basic surgical technical skill.
AB - BACKGROUND: Rapid improvements in computer technology allow us to consider the
use of computer-assisted learning (CAL) for teaching technical skills in surgical
training. The objective of this study was to compare in a prospective, randomized
fashion, CAL with a lecture and feedback seminar (LFS) for the purpose of
teaching a basic surgical skill. METHODS: Freshman medical students were randomly
assigned to spend 1 hour in either a CAL or LFS session. Both sessions were
designed to teach them to tie a two-handed square knot. Students in both groups
were given knot tying boards and those in the CAL group were asked to interact
with the CAL program. Students in the LFS group were given a slide presentation
and were given individualized feedback as they practiced this skill. At the end
of the session the students were videotaped tying two complete knots. The tapes
were independently analyzed, in a blinded fashion, by three surgeons. The total
time for the task was recorded, the knots were evaluated for squareness, and each
subject was scored for the quality of performance. RESULTS: Data from 82 subjects
were available for the final analysis. Comparison of the two groups demonstrated
no significant difference between the proportion of subjects who were able to tie
a square knot. There was no difference between the average time required to
perform the task. The CAL group had significantly lower quality of performance (t
= 5.37, P <0.0001). CONCLUSIONS: CAL and LFS were equally effective in conveying
the cognitive information associated with this skill. However, the significantly
lower performance score demonstrates that the students in the CAL group did not
attain a proficiency in this skill equal to the students in the LFS group.
Comments by the students suggest that the lack of feedback in this model of CAL
was the significant difference between these two educational methods.
PMID- 9645784
TI - Does volume of patients seen in an outpatient setting impact test scores?
AB - BACKGROUND: Methods of teaching surgery in the outpatient setting and means to
measure the effectiveness of these methods have not been defined. This study was
designed to evaluate the impact of number of outpatient encounters on test scores
for third-year medical students. METHODS: Students rotating on the required third
year surgery clerkship between July 1994 and June 1996 kept a log of their
activities including number of patients seen in clinic, number of cases scrubbed,
and pages read. At the end of the rotation the students were given an essay
examination and a multiple-choice examination. The data were analyzed looking for
correlation between examination scores and volume of patients seen. United States
Medical Licensing Examination (USMLE) Step 1 scores were used as a baseline
measure to compare the rotation groups. RESULTS: USMLE scores did not differ
between groups. Mean essay examination scores varied significantly between some
rotation groups, but did not follow a pattern. There was no correlation between
the number of patients seen in clinic and essay examination scores. There was a
significant correlation between essay score and USMLE Step 1 score (Pearson's r =
0.398) and between essay and multiple-choice examination scores (Pearson's r =
0.313). There was a significant negative correlation between number of patients
seen in clinic and number of cases scrubbed (Pearson's r = -0.347). CONCLUSIONS:
Participation in outpatient surgery clinics did not result in improved
performance on written examinations in this surgery clerkship. To achieve the
most benefit from the outpatient clinic, objectives of the experience need to be
determined and appropriate tools used to measure their successful achievement.
PMID- 9645785
TI - Is a mandatory general surgery rotation necessary in the surgical clerkship?
AB - BACKGROUND: Changes in the spectrum of general surgery and the delivery of
surgical care have placed the requirement for a mandatory general surgery
rotation in the surgical clerkship in question. METHODS: We tested the hypothesis
that equal mastery of surgical clerkship objectives can be obtained in a
clerkship with and without general surgery. Students chose any two surgical
rotations and were assessed by written examination, objective structured clinical
examination (OSCE), ward evaluations, self-assessment objectives questionnaire,
and satisfaction survey. RESULTS: Data for 54 students showed no differences in
scores between groups on any parameter. No specific concerns related to the
absence of general surgery were identified. CONCLUSIONS: Effective undergraduate
surgical education can be offered in many specialty settings. Removal of the
requirement for general surgery in clerkship may lead to a more effective use of
all educational opportunities. A careful analysis of local programs and
facilities is necessary before suggesting this change to other institutions.
PMID- 9645786
TI - Can a one-day workshop alter surgeons' teaching practices?
AB - BACKGROUND: A 1-day workshop, consisting of five sections with small group
discussions and opportunities for practical application of participants'
knowledge, was developed to enhance the teaching skills of practicing surgeons.
Immediate and long-term follow-up surveys were completed by the participants.
METHODS: Post-workshop evaluations were obtained from all participants who took
the workshop; follow-up surveys were mailed 4 to 6 months later. RESULTS:
Workshop quality was rated as good (25%) or excellent (75%) by all participants.
Follow-up survey results indicated that many participants had rarely/never
utilized cited references, looked for additional resources on specific topics, or
referred to the section syllabus/handout materials provided during the workshop.
However, 100% of the participant respondents reported that they had changed the
way they teach as a result of their workshop attendance. CONCLUSION: An
abbreviated course on surgical education can result in long-term changes in the
participants' perceptions of their teaching practices. Further study is required
to determine if these perceived changes in teaching practices, which the
participants have directly attributed to their workshop attendance, have resulted
in measurable improvement in their effectiveness and efficiency as teachers.
PMID- 9645787
TI - Analysis of case-control studies of the efficacy of screening for cancer: How
should we deal with tests done in persons with symptoms?
PMID- 9645788
TI - Maternal smoking, body mass index, and neural tube defects.
AB - The Swedish health registries were used to investigate a possible effect on the
incidence of neural tube defects (NTDs) of maternal smoking and maternal body
mass index (BMI) (kg/m2). Among 1,199,701 infants born in 1983-1993 with known
smoking exposure in early pregnancy, 621 infants with NTDs were selected. After
controlling for year of birth, maternal age, parity, education level, BMI, and
immigrant status (yes/no), a highly significant, protective effect of maternal
smoking on the incidence of NTDs was found. The adjusted odds ratios (OR) and
(95% confidence intervals (CI)) for maternal smoking among infants with NTDs
(total), anencephaly, and spina bifida were 0.75 (0.61-0.91), 0.49 (0.28-0.85),
and 0.76 (0.61-0.95), respectively. A protective dose-response effect of smoking
was indicated but was not statistically significant. The association between NTDs
and maternal BMI found in earlier studies was supported. Women with BMI >26.0
were found to be at higher risk of having an infant with NTD compared with women
in other BMI classes (adjusted OR=1.35, 95% CI 1.00-1.83). For women with BMI >
or =29, the corresponding odds ratio was 1.29 (0.81-2.05). No obvious explanation
was found, either for the detected association between NTDs and BMI, or for the
protective effect of maternal smoking.
PMID- 9645789
TI - Epidemiologic interpretation of artificial neural networks.
AB - Multilayer neural networks have been faulted for functioning as "black boxes" and
for failing to assess the relative importance of the input factors. The aim of
this paper is to illustrate how neural networks can classify individuals. The
authors investigated the role of weights in the formation of neural networks'
decision surfaces and decision regions. The data used were from a case-control
study. Two strong determinants of case status were used as input "neurons." Zero,
three, and five hidden neurons were used to explore the effect of the number of
hidden neurons on the decision surfaces and regions. Mapping of input and output
spaces revealed that three hidden neurons were insufficient to fully discriminate
cases from controls. Five hidden neurons may be optimal, but at the cost of
possible over-fitting. The more complex neural networks were very effective at
defining regions of uniform risk in the plane of the initial covariates, and at
assigning risk levels. The authors speculate that neural networks will prove
useful in epidemiologic problems that require pattern recognition or complicated
classification techniques, and that they will be unfavorable in problems that
involve distinct effects of distinguishable predictors.
PMID- 9645790
TI - Correction for biases in a population-based study of family history and coronary
heart disease. The Newcastle Family History Study I.
AB - In this paper, the authors report on the design of a population-based case
control study of family history as a risk factor for coronary heart disease
(CHD). They studied the characteristics of subjects who completed a detailed
family history questionnaire in 1992-1994 as well as the accuracy of recall of
family history in order to quantify both selection and recall biases. Coronary
disease cases were enrolled through the Newcastle MONICA Project (Monitoring
Trends and Determinants in Cardiovascular Disease), which registered all
suspected heart attacks and sudden cardiac deaths in the Lower Hunter region of
New South Wales, Australia, between August 1984 and March 1994. Controls were
selected at random from the New South Wales electoral roll. The response rate was
76% in cases and 62% in controls; the major factor associated with participation
in the study was perceived family history of CHD, more so in the control series
than in the case series. Accuracy was determined by comparing information
obtained from the proband with that recorded on death certificates. In first
degree relatives, sensitivity of CHD recall was 85% (95% confidence interval (CI)
74-92%) in cases and 95% (95% CI 84-99%) in controls, while specificity was 59%
(95% CI 49-69%) and 74% (95% CI 65-82%), respectively. The net bias in both
selection and recall is toward the null and hence the comparisons provide a
conservative estimate of risk of CHD associated with a positive family history.
PMID- 9645791
TI - Risk associated with various definitions of family history of coronary heart
disease. The Newcastle Family History Study II.
AB - The authors carried out a population-based case-control study to estimate the
risk of an acute coronary disease event associated with various definitions of a
family history of coronary heart disease (CHD). A detailed family history
questionnaire was completed by 403 cases and 236 controls in Newcastle, New South
Wales, Australia from 1992 to 1994. Odds ratios of an acute coronary disease
event adjusted for proband age and sex ranged from 2.7 (95% confidence interval
(CI) 1.8-4.1) for the simplest definition (one or more first-degree relatives
with CHD at any age) to 5.4 (95% CI 1.7-16.8) for the most stringent definition
(two or more first-degree relatives with CHD before age 55 years). In a series of
nested models, the authors examined the improvement in model fit as each
component of the detailed family history was added. Additional information was
provided by accounting for "don't know" responses, the number of affected
relatives, the age of the affected relative, and whether the first-degree
relative was a sibling rather than a parent. The results were similar when the
data were analyzed as a cohort design with proband disease status as the exposure
variable. The authors suggest that, to facilitate preventive efforts in a
population, more detailed family history definitions should be used to better
target high risk subjects.
PMID- 9645792
TI - Retrospective analysis of birth weight and prostate cancer in the Health
Professionals Follow-up Study.
AB - The authors retrospectively evaluated the relation between birth weight and
prostate cancer (1986-1994) among 21,140 men of the Health Professionals Follow
up Study who reported in 1994 their weight at birth. No relation between birth
weight and prostate cancer (n=545) was observed in multivariate logistic models.
For high stage/grade tumors (n=213), compared with birth weights <7.0 lbs (<3,175
g), the relative risks were 1.20 (95% confidence interval (CI) 0.79-1.83) for 8.5
9.9 lbs (3,855.6-4,490.6 g) and 1.30 (95% CI 0.80-2.10) for > or = 10 lbs (> or =
4,536 g). These findings do not support an overall association between birth
weight and prostate cancer incidence, but the possibility of a modest positive
association between birth weight and high stage/grade prostatic cancer cannot be
excluded.
PMID- 9645793
TI - Gender differences in total and allergen-specific immunoglobulin E (IgE)
concentrations in a population-based cohort from birth to age four years.
AB - While serum immunoglobulin E (IgE) concentration has been shown to be related to
allergic disease, there have been few studies of the natural history of IgE
development in young children. This study compared total and allergen-specific
serum IgE concentrations, by gender, from birth through 4 years of age using a
population-based cohort of normal children followed from 1987 to 1993. Subjects
were enrolled from a geographically defined area through membership in a large
health maintenance organization, and they resided in the northern suburbs of
Detroit, Michigan. Total IgE concentrations were measured at birth and at 2 and 4
years of age. Specific IgE concentrations to selected common inhalant allergens
(dust mite (Dematophagoides farinae), cat, ragweed (Ambrosia artemisiifolia), and
timothy grass (Pheleum pratense)) were measured at 2 and 4 years of age. Total
IgE increased with age from birth to 4 years for boys and girls, and was higher
in boys at 2 and 4 years of age. Girls demonstrated significant increases in IgE
to mite and cat and decreases in IgE to ragweed and timothy from 2 to 4 years of
age, whereas there was little change for boys except an increase in IgE to
ragweed. Differences in IgE development between young boys and girls may
partially account for the higher prevalence of asthma in boys than in girls.
PMID- 9645794
TI - Reliability of self-reported sexual behavior in human immunodeficiency virus
(HIV) concordant and discordant heterosexual couples in northern Thailand.
AB - A partner study was conducted in northern Thailand between March 1992 and June
1996 which included data that allowed an assessment of the reliability of self
reports of sexual behavior and contraceptive use among heterosexual couples. The
authors enrolled 529 couples among whom all male subjects were human
immunodeficiency virus (HIV) seropositive voluntary blood donors and their female
sexual partners were either HIV infected (n=246) or HIV seronegative (n=283). The
levels of agreement within couples were assessed for recency of last sexual
intercourse, sexual activity in the prior year, and contraceptive practices. For
HIV discordant couples, a prospective study was conducted to examine risk factors
for HIV transmission, the primary goal of the study. This allowed assessment of
reliability of inter-partner reports over 6-12 months. Overall, agreement among
couples was good for common sexual practices, especially vaginal intercourse and
time since last intercourse, but was lower for condom use. Anal and oral sex were
infrequently reported by these couples and there was greater disagreement for the
occurrence of these practices. Partner agreement for contraceptive histories was
good to excellent. Prospective data showed less frequent intercourse and more
condom use but reliability remained good. Common sexual practices may be reliable
for both HIV concordant and discordant couples in studies estimating prevalent
infection. Estimates of incident heterosexually transmitted HIV may be made with
greater reliability by studies which include assessment of reports of risk
behavior by each member of a couple than studies of individuals.
PMID- 9645795
TI - Relation of nutrition to bone lead and blood lead levels in middle-aged to
elderly men. The Normative Aging Study.
AB - The relations of nutritional factors to lead accumulation in the body were
examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the
Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead,
tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and
32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for
age, education level, smoking, and alcohol consumption, men in the lowest
quintile of total dietary intake levels of vitamin D (including vitamin
supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g
and 6.0 microg/g higher than men with intake in the highest quintile (> or =589
i.u./day). Higher calcium intake was associated with lower bone lead levels, but
this relation became insignificant when adjustment was made for vitamin D. The
authors also observed inverse associations of blood lead levels with total
dietary intake of vitamin C and iron. When analyses were controlled for patella
lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake
quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men
in the highest quintile (> or =339 mg/day), while men in the lowest iron intake
quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men
in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary
intake of vitamin D may increase lead accumulation in bones, while lower dietary
intake of vitamin C and iron may increase lead levels in the blood.
PMID- 9645797
TI - Prevention of primary islet isograft nonfunction in mice with pravastatin.
AB - BACKGROUND: Nonspecific inflammatory damage in the early stages of
transplantation is the major cause of primary islet graft nonfunction. Using
murine isografts, we attempted to prevent this islet graft damage by treating
recipients with pravastatin (Pravacol), a 3-hydroxy-3-methylglutaryl-coenzyme A
reductase inhibitor. Nicotinamide was also tested to determine the synergistic
effect of both agents. METHODS: Unpurified newborn BALB/c islets, ranging in
number from 1800 to 2500, were transplanted into the left renal subcapsular space
of a syngeneic adult mouse made diabetic with streptozotocin. Recipient mice were
divided into the following four groups, based on treatment protocols: treatment
with 40 mg/kg pravastatin (group 1), 500 mg/kg nicotinamide (group 2), 40 mg/kg
pravastatin and 500 mg/kg nicotinamide (group 3), and vehicle alone (group 4).
Pravastatin and nicotinamide were administered orally every day for 14 days,
starting on the day of transplantation (day 0). Nonfasting blood glucose levels,
urine glucose levels, and the intravenous glucose tolerance test were used to
monitor the diabetic state. The reversal of diabetes was defined by normoglycemia
and negative urine glucose maintained for more than 7 days. RESULTS: After islet
transplantation, levels of blood and urine glucose were significantly lower in
groups 1 and 3, compared with those in group 4. K-values of an intravenous
glucose tolerance test performed on day 14 were significantly higher in groups 1
and 3 than those of group 4. Reversal of diabetes had occurred in 63% of mice in
group 1 and 67% in group 3, levels that were higher than those in group 2 (17%)
and group 4 (0%) (P<0.02, groups 1 and 3 vs. group 4). Histological examination
of grafts, biopsied on day 21, revealed well preserved islets with little sign of
inflammation in groups 1 and 3, whereas grafts in groups 2 and 4 contained
broken, smaller islets surrounded by severe fibrosis and mononuclear cell
infiltration. CONCLUSION: Our results in mice have shown the effectiveness of
pravastatin for protecting islets from nonspecific inflammatory damage.
Nicotinamide did not show a synergistic effect with pravastatin at the dosage
used in this study. These results indicate that pravastatin may be a useful agent
for clinical islet transplantation.
PMID- 9645796
TI - Prolonged acceptance of concordant and discordant xenografts with combined CD40
and CD28 pathway blockade.
AB - BACKGROUND: The prompt and vigorous immune response to xenogenic tissue remains a
significant barrier to clinical xenotransplantation. Simultaneous blockade of the
CD28 and CD40 costimulatory pathways has been shown to dramatically inhibit the
immune response to alloantigen. METHODS: . In this study, we investigated the
ability of simultaneous blockade of the CD28 and CD40 pathways to inhibit the
immune response to xenoantigen in the rat-to-mouse and pig-to-mouse models.
RESULTS: Simultaneous blockade of the CD28 and CD40 pathways produced marked
inhibition of the cellular response to xenoantigen in vivo and produced long-term
acceptance of xenogeneic cardiac and skin grafts (rat-to-mouse), and markedly
suppressed an evoked antibody response to xenoantigen. In addition, this strategy
significantly prolonged the survival of pig skin on recipient mice. CONCLUSIONS:
Long-term hyporesponsiveness to xenoantigen across both a concordant and
discordant species barrier, measured by the stringent criterion of skin grafting,
can be achieved using a noncytoablative treatment regimen.
PMID- 9645798
TI - A new and simple technique of total hepatic ischemia in the mouse.
AB - BACKGROUND: A model of total hepatic ischemia is currently not available in mice.
Models described in rats using portosystemic shunts to achieve total ischemia
have been notoriously difficult. In mice, the problem is compounded further when
using this type of technique because of the small size of the animal. A new
technique is described combining partial hepatectomy with clamping of the remnant
liver. METHODS: A partial (30%) hepatectomy is performed with resection of the
caudate, right lateral, and quadrate lobes, and papillary process. Vascular
microclamps are placed across the pedicles of the median and left lateral lobe at
the level of the hilum to achieve total ischemia. Spontaneous portocaval shunts
through caudate branches and collateral vessels prevent mesenteric congestion.
Animals were studied for survival. RESULTS: The procedure consistently took less
than 30 min (25+/-2 min), and no bleeding of the resected tissue was observed.
Evidence for total hepatic ischemia and spontaneous shunts was demonstrated by
the use of an intraportal dye. All animals survived 60 min of ischemia, whereas
all died after 90 min of ischemia. CONCLUSION: This is a technically simple and
rapid procedure to perform. In the current environment of multiple knockout mice
and bioreagents that are available, a model of this type is essential.
PMID- 9645799
TI - Mouse parvovirus infection potentiates allogeneic skin graft rejection and
induces syngeneic graft rejection.
AB - BACKGROUND: The recently identified autonomous mouse parvovirus designated mouse
parvovirus-1 (MPV-1) persists in adult BALB/c mice for at least 9 weeks, infects
lymphoid tissues, interferes with the ability of cloned T cells to proliferate,
and exhibits immunomodulatory properties. As a consequence of these findings, the
present studies were undertaken to characterize further the inmunomodulatory
effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro.
METHODS: To evaluate the effect of MPV-1 infection on CD8+ T cell-mediated
responses, BALB/c-H2dm2 mice were infected after transplantation of allogeneic
BALB/c skin. RESULTS: MPV-1 potentiated the rejection of allogeneic skin grafts.
This potentiation was not a result of virus infecting the cellular or vascular
component of the graft as determined by in situ hybridization, but was mediated
by T cells. However, the proliferative capacity of alloantigen-reactive
lymphocytes from graft-sensitized infected mice was diminished. MPV-1 also
induced the rejection of syngeneic skin grafts, and T cells from these infected
graft-sensitized mice lysed syngeneic P815 target cells. CONCLUSIONS: These
results suggest that MPV-1 infection of skin-grafted mice may disrupt normal
mechanisms of peripheral tolerance and provide a unique model to study virus
induced autoimmunity.
PMID- 9645800
TI - Inhibitory effect of Multiglycosidorum tripterygii on coronary arteriosclerosis
after heart transplantation.
AB - BACKGROUND: Graft coronary arteriosclerosis (GCA) is the major limiting factor
for long-term survival after heart transplantation. In this study, we
investigated the effect of Multiglycosidorum tripterygii (MT) on GCA and platelet
derived growth factor A (PDGF-A) mRNA expression of transplanted hearts. METHODS:
Two groups of Lewis rats (n=7/group) underwent heterotopic heart transplantation
from Wistar-King donors and were treated with either cyclosporine (CsA;10
mg/kg/day) or MT (30 mg/kg/ day). Histological evaluations of rejection and
coronary arteriosclerosis, as well as Northern blot analysis on graft PDGF-A mRNA
expression were made 60 days after transplantation. RESULTS: Morphometric results
indicated no significant difference in rejection between the CsA- and MT-treated
groups. However, the extent of GCA in the MT-treated group was significantly less
than that seen in the CsA-treated group (P<0.01). The expression of PDGF-A mRNA
of cardiac allograft was also significantly suppressed in the MT-treated group
when compared with the CsA-treated group (P<0.01). CONCLUSION: MT is superior to
CsA in preventing graft coronary arteriosclerosis, and this efficacy is probably
associated with the depressed expression of graft PDGF-A mRNA in the MT-treated
group.
PMID- 9645801
TI - A blinded, long-term, randomized multicenter study of mycophenolate mofetil in
cadaveric renal transplantation: results at three years. Tricontinental
Mycophenolate Mofetil Renal Transplantation Study Group.
AB - BACKGROUND: Three large-scale clinical trials conducted in North America, Europe,
and Australia showed that mycophenolate mofetil (MMF) decreases the incidence of
acute renal allograft rejection in the first 6 months after transplant compared
with placebo or azathioprine. This study extends the randomized, prospective,
double-blind trial of MMF conducted by the Tricontinental Mycophenolate Mofetil
Renal Transplantation Study Group. METHODS: Patients (n=503) were randomized to
receive 100-150 mg of azathioprine (AZA) (n=166), 2 g of MMF (n=173), or 3 g of
MMF (n=164) per day, in conjunction with cyclosporine and prednisone from the
time of transplantation. RESULTS: During the first 6 months, the incidence of
biopsy-proven acute graft rejection (BPR) was reduced by approximately 50% in the
MMF 2 g (19.7%) and MMF 3 g (15.9%) groups compared with the AZA group (35.5%).
The incidence of treatment failure during the first 6 months, including BPR,
death, graft loss, and early withdrawal without prior BPR, was significantly
decreased: AZA, 50%, compared with MMF 2 g, 38.2% (P=0.0287), and MMF 3 g, 34.8%
(P=0.0045). At 3 years after transplant, both intent-to-treat and on-study
(censoring at 90 days after treatment) analyses of graft and patient survival
showed a trend toward advantage for MMF 2 g and 3 g vs. AZA (intent-to-treat:
81.9% and 84.8% vs. 80.2%; on-study: 84.0% and 86.4% vs. 82.7%), although this
trend did not reach statistical significance. Rejection was the principal cause
of graft loss in all groups: AZA, 9.9%; MMF 2 g, 5.8%; and MMF 3 g, 3.0%. Graft
function (intent-to-treat and on-study) was comparable in all three groups at 3
years. Gastrointestinal toxicity, leukopenia, and tissue-invasive cytomegalovirus
disease were more common in the MMF 3 g group both during and after the first
posttransplant year. Lymphoproliferative disorders were diagnosed in one AZA
(0.6%), two MMF 2 g (1.2%), and three MMF 3 g (1.8%) patients. Other (non
lymphoproliferative disorders, noncutaneous) malignancies occurred in six AZA
(3.7%), four MMF 2 g (2.3%), and nine MMF 3 g (5.5%) patients. Mortality was
comparable in all three groups (AZA, 8.6%; MMF 2 g, 4.7%; MMF 3 g, 9.1%) by 3
years of follow-up. CONCLUSION: MMF significantly reduced the incidence of
rejection in the first 6 months, but there was not a significant improvement in
graft survival throughout the 3 years after cadaver kidney transplantation.
PMID- 9645802
TI - Randomized, double-blind, one-year study of the safety and tolerability of
cyclosporine microemulsion compared with conventional cyclosporine in renal
transplant patients. International Sandimmun Neoral Study Group.
AB - BACKGROUND: A microemulsion formulation of cyclosporine, Neoral, has been
developed to overcome the problems associated with the poor and variable
absorption of the traditional oil-based oral formulation, Sandimmune. The present
study was conducted to compare the safety and tolerability of Neoral versus
Sandimmune in maintenance renal transplant recipients over 1 year, and to assess
the number of dose adjustments necessary to maintain trough cyclosporine
concentrations within the desired therapeutic range. METHODS. Patients on
Sandimmune were randomized to be converted to Neoral (n=373) or remain on
Sandimmune (n=93) for 12 months. RESULTS: The proportion of patients needing dose
increases to maintain cyclosporine trough levels within the desired range was
significantly higher in the Sandimmune group during the first 3 months of the
study, whereas the number of patients needing dose reductions was similar in both
groups throughout the study period. There were no differences between the groups
in terms of changes in blood pressure, serum creatinine levels, or other
laboratory parameters. No significant differences in the incidence of adverse
events known to be related to cyclosporine were observed between the treatment
groups. More adverse events were causally related to Neoral than to Sandimmune by
the investigators. However, overall, there were no clinically relevant
differences between the treatment groups in the main safety and tolerability
variables. CONCLUSIONS: The results of this study in maintenance renal transplant
patients suggest that the improved pharmacokinetic characteristics of the
microemulsion formulation of cyclosporine, Neoral, may facilitate the clinical
management of cyclosporine immunosuppression, compared with the traditional
formulation, Sandimmune. Furthermore, there is no evidence that the average
improved bioavailability of Neoral has a negative impact on the main safety and
tolerability variables, as no significant differences in graft function, the
incidence of rejections, and most adverse events were seen.
PMID- 9645803
TI - Use of aminophylline and enalapril in posttransplant polycythemia.
AB - BACKGROUND: Posttransplant polycythemia (PTP) affects 6-30% of renal transplant
recipients and can result in thromboembolic disease. The pathogenesis of PTP
remains unknown and may be multifactorial. Although phlebotomy has previously
been the treatment for PTP, drugs such as adenosine receptor antagonists or
angiotensin-converting enzyme inhibitors can be used to control PTP. METHODS: The
authors performed a prospective study of two different drugs to treat PTP:
aminophylline and enalapril. Twenty-seven patients with PTP lasting more than 6
months were evaluated. During phase 1, aminophylline was compared with enalapril.
The patients sequentially received aminophylline and enalapril during 12-week
periods, intercalated by 12-week periods of no drugs. During phase 2, enalapril
was administered for 12 weeks. RESULTS: From January 1984 to December 1993, 110
of 333 patients with PTP lasting more than 6 months (33%) developed polycythemia,
and 27 patients were included in the present study. In phase 1, aminophylline had
no effect on PTP. Enalapril promoted an erythropoiesis inhibition, characterized
by a decrease in hematocrit and an increase in iron stores and ferritin levels.
After withdrawal of enalapril, the hematocrit increased and the iron stores
decreased. In phase 2, there was a progressive reduction in hematocrit after the
4th week of therapy. The lowest hematocrit was observed in the 12th week and then
enalapril was stopped, leading to a subsequent rise in hematocrit. Erythropoietin
levels and renal function remained constant during all periods of both phases of
the study. CONCLUSION: The use of adenosine antagonists was ineffective to treat
PTP in our series. However, treatment with enalapril promoted an erythropoiesis
inhibition, demonstrated by a reduction in hematocrit, hemoglobin, red blood cell
count, and reticulocyte count, associated with an increase in iron stores. This
response occurred independently from erythropoietin levels or hemodynamic graft
changes.
PMID- 9645804
TI - A good alternative to reduce the kidney shortage: kidneys from nonheartbeating
donors.
AB - BACKGROUND: Because of the shortage of kidneys available for transplantation, we
began in 1985 to harvest kidneys from non-heartbeating (NHB) donors. METHODS: We
compared the results of a group of 66 kidney recipients from NHB donors (NHB
group) with 122 kidney recipients from heartbeating donors (HB group). We
analyzed, in the NHB group, the influence of ischemia times in graft survival and
we tested the best cut-offs by receiver operating characteristic curves. We also
studied, using a univariate and multivariate Cox hazard model, the capacity of
different variables to predict graft loss. RESULTS: Patient and graft survival
were similar in both groups during the follow-up. The percentage of delayed graft
function was the only significant difference between both groups (NHB group 62%
vs. HB group 32%; P=0.0001). Delayed graft function, in the NHB group, is
influenced by the warm ischemia time, which is directly related to the number of
days to achieve a serum creatinine<300 mmol/L (P=0.0001). The best cut-off times
in this group were 45 min for warm ischemia time and 22 hr for cold ischemia
time. Recipients have a greater likelihood of losing the graft beyond those
limits (P=0.017, relative risk: 7.3). The incidence of acute rejection was
similar in both groups, and it was the only predictor factor of graft loss in the
complete series of patients (P=0.0001), in the NHB group (P=0.007), and in the HB
group (P=0.02). CONCLUSIONS: Reducing the incidence of acute rejection and
shortening ischemia time are conditions needed to guarantee a long graft survival
of kidneys from NHB donors.
PMID- 9645806
TI - Clinical significance of viral load in the diagnosis of cytomegalovirus disease
after liver transplantation.
AB - In a cohort of 43 liver transplant recipients who did not receive antiviral
prophylaxis, qualitative and quantitative polymerase chain reactions (PCRs) from
peripheral blood were prospectively compared to determine their value in the
diagnosis of established cytomegalovirus (CMV) disease and for the early
detection of CMV replication as a marker for preemptive antiviral therapy. Using
a cutoff of 7000 copies of CMV DNA per sample, the specificity and positive
predictive values of qualitative PCR for the diagnosis of established CMV disease
increased from 33% to 89% and from 54% to 82%, respectively, without reducing the
100% sensitivity and negative predictive value. By contrast, quantification of
viral load provided no additional advantage to qualitative PCR for the early
diagnosis of CMV infection before development of disease.
PMID- 9645805
TI - Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric
heart transplant recipients.
AB - BACKGROUND: Few reports document long-term results of pediatric cardiac
transplantation in which triple therapy (cyclosporine, azathioprine, and
corticosteroids) was the mainstay of immunosuppression. This report details a
single center's pediatric transplant experience and analyzes the relative
contributions of selected pre/posttransplant risk factors on long-term morbidity
and mortality. METHODS: Retrospective data were collected for all non-neonatal
pediatric transplant recipients including: presenting diagnosis, cardiac
hemodynamics (particularly pulmonary vascular resistance index), donor ischemic
time, occurrence of postoperative infections, episodes of allograft rejection,
incidence of posttransplant lymphoproliferative disease or coronary artery
disease (CAD), and overall survival. Analysis of single variables and a Cox
proportional hazards model were utilized to determine the impact of
pre/posttransplant risk factors on long-term survival. RESULTS: From 1984 to
1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who
had inoperable complex congenital heart disease, underwent cardiac
transplantation and received triple-drug immunosuppression. Orthotopic
transplantation was performed unless the pulmonary vascular resistance index
remained >6 um2 (despite use of pulmonary vasodilator). One patient required
heterotopic transplantation. Average donor ischemic time was 217 min. An average
of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months).
No patient developed posttransplant lymphoproliferative disease, but 22 patients
(34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10
years, respectively. Of outcome variables analyzed, rejection frequency was
significantly increased in patients who subsequently developed CAD, but the
presence of CAD was not significantly correlated with mortality. CONCLUSION:
Triple-drug-based immunosuppressive maintenance therapy in pediatric heart
transplant recipients results in good long-term graft survival.
PMID- 9645807
TI - Partial T-cell activation and anergy induction by polyclonal antithymocyte
globulin.
AB - BACKGROUND: Polyclonal antithymocyte globulins have been assumed to deplete or
sequester immunocompetent T cells. We investigated the hypothesis that anti-human
thymocyte globulin (ATGAM)-mediated immunosuppression is delivered via
nondepletive, immunologically specific actions as a consequence of simultaneous
engagement of multiple T cell receptors. METHODS: Purified T cells obtained from
healthy volunteers or renal transplant recipients receiving their first dose of
ATGAM were evaluated for proliferative responses and cell-mediated lympholysis.
ATGAM binding and receptor expression were determined by flow cytometry.
Cytokines and ATGAM levels were measured by enzyme-linked immunosorbent assay.
RESULTS: ATGAM-treated T cells showed significant dose-dependent inhibition of
proliferation in vitro at concentrations comparable to those measured in
patients. Effectors raised after ATGAM treatment failed to develop cytotoxicity.
Supernatant interleukin (IL)-2 levels in ATGAM-treated cultures were
significantly reduced (P<0.01 vs. control). IL-4 was not significantly altered.
In vivo studies confirmed significant ATGAM-mediated inhibition of proliferative
responses. Concanavalin A and OKT3-driven proliferation were reduced 30-60% by
ATGAM. Flow cytometry showed that ATGAM recognized multiple cell surface
receptors and resulted in markedly increased IL-2R and CD28 expression in the
absence of proliferation, demonstrating partial T-cell activation. ATGAM
synergized with phorbol myristate acetate to produce strong proliferation, which
suggests that it provides a calcium-based signal resulting in anergy.
CONCLUSIONS: ATGAM recognizes and cross-links multiple cell surface receptors and
costimulator molecules on human T cells. Simultaneous engagement by ATGAM in the
context of allogeneic or mitogenic stimulation leads to partial T-cell activation
and anergy.
PMID- 9645808
TI - Contribution of donor-specific antibodies to acute allograft rejection: evidence
from B cell-deficient mice.
AB - BACKGROUND: The role of T lymphocytes in acute allograft rejection is well
established. The involvement of B lymphocytes in this process, however, is more
controversial. A series of reports showed that mice without a functional B-cell
compartment rejected allografts with the same kinetics as control animals. In
rats, however, alloantibodies were found to play a decisive role in allograft
rejection. To provide an explanation for the discrepant results, we readdressed
the role of B cells and antibodies in mice with disrupted immunoglobulin mu chain
genes. The use of cyclosporine (CsA), which strongly suppresses T cells, allowed
us to focus specifically on the function of B cells. METHODS: C57BL/6 mice
rendered B cell deficient by targeted disruption of the immunoglobulin mu chain
gene (referred to as microMT/microMT mice) and microMT/+ control mice with one
functional mu chain were heterotopically transplanted with fully MHC-disparate
BALB/c hearts. CsA was administered subcutaneously by Alzet osmotic pumps. Normal
and immune serum specific for donor hearts was given to assess the role of
antibodies in the rejection process. RESULTS: Both B cell-deficient
microMT/microMT and heterozygous microMT/+ mice were found to reject transplanted
hearts within a similar period of time. In contrast, when T cells were partially
suppressed with CsA, graft survival was significantly prolonged in
microMT/microMT mice as compared with heterozygous controls. Passive transfer of
donor-specific immune serum, obtained from microMT/+ animals rejecting allogeneic
hearts, to CsA-treated microMT/microMT mice significantly accelerated allograft
rejection as opposed to recipients treated with normal serum. CONCLUSIONS: B
lymphocytes and antibodies play an important role in acute allograft rejection
particularly when the dominant T-cell compartment is partially suppressed.
PMID- 9645809
TI - Posttransplant liver granulomatosis associated with hepatitis C?
AB - BACKGROUND: Liver granulomatosis is an occasional finding in posttransplant liver
biopsies. Its diagnosis is made more difficult by the variety of conditions that
can lead to it. In the nontransplant setting, the association of liver
granulomatosis and hepatitis C virus (HCV) infection has occasionally been
described. METHODS: We describe the case of a patient with a liver
transplantation for an HCV-associated cirrhosis who developed an alteration of
liver tests. Granulomatosis was detected on the liver biopsy. RESULTS: Other
causes of granulomatosis were satisfactorily excluded. The development of the
lesions coincided with a viral flare-up. CONCLUSION: We think that HCV can be
listed among the possible causes of liver granulomas in the posttransplant
setting and that it must be considered in the differential diagnosis of this
condition.
PMID- 9645810
TI - Domino hepatic transplantation using the liver from a patient with familial
amyloid polyneuropathy.
AB - BACKGROUND: In transplantation, novel methods are required to augment the supply
of donor organs. We report the first domino liver transplant in which a patient
with familial amyloid polyneuropathy (FAP) received an orthotopic split liver
graft, and her explanted liver was donated to another patient. Three successful
liver transplants were thus achieved from the one cadaver liver. PATIENTS AND
METHODS: A cadaveric donor liver was split and the left lobe was grafted into a
child with biliary atresia. The right lobe was transplanted into a woman with FAP
associated with the transthyretin Met30 variant. Her own otherwise healthy liver
was donated to a patient with cirrhosis and hepatocellular carcinoma. RESULTS:
Fifteen months after transplantation, all three recipients are well with normal
liver function. The domino recipient developed inferior vena cava stricturing at
the level of anastomosis after surgery with resultant ascites, requiring
dilatation and LeVeen shunt insertion. Serum amyloid P component scintigraphy
showed amyloid regression in the domino donor and to date has not identified any
amyloid deposits in the recipient, who also remains free of tumor recurrence.
CONCLUSIONS: Domino transplantation using the livers from patients with FAP may
be justified for patients whose disease condition precludes a long spell on the
waiting list, including those with hepatic malignancies and those for whom
palliation rather than long-term cure is the aim.
PMID- 9645811
TI - Efficacy of lamivudine re-treatment in a patient with hepatitis B virus (HBV)
recurrence after liver transplantation and HBV-DNA breakthrough during the first
treatment.
AB - BACKGROUND: Transplantation for terminal hepatitis B virus (HBV) disease is
aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a
new nucleoside analog, is a potent inhibitor of HBV synthesis, but its use may
lead to the emergence of HBV-DNA polymerase mutants resistant to the drug.
METHODS AND RESULTS: We describe the case of a patient who developed an HBV
recurrence after liver transplantation and was treated with lamivudine. An HBV
DNA breakthrough occurred 7 months after the start of therapy, and the drug was
stopped after 9 months. The molecular state of HBV-DNA was analyzed, and a
mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV
DNA polymerase was identified. Nine months after the suspension of lamivudine the
patient experienced a new hepatic attack accompanied by high HBV-DNA levels.
Lamivudine was given again. Serum HBV-DNA levels normalized after 45 days of re
treatment, but lamivudine-resistant mutants were again the prevalent viral
population after 3 months. CONCLUSIONS: The case described suggests that
retherapy with lamivudine after a first emergence of YMDD mutants is temporarily
effective in recontrolling HBV synthesis but ultimately induces the accelerated
reemergence of a prevalently mutant population of HBV. This emphasizes the need
for combined antiviral therapy.
PMID- 9645812
TI - Pathogenesis of early operative site infections after orthotopic liver
transplantation.
AB - BACKGROUND: We hypothesized that operative site infections after orthotopic liver
transplantation arise from bacteria in bile or jejunum. METHODS: To ascertain the
validity of this hypothesis and to assess the effect of systemic antibiotic
prophylaxis, we obtained intraoperative cultures of peritoneum, fascia, explant
and donor liver bile, and jejunal lumen in 77 liver transplantations, and we
monitored outcome. RESULTS: Pathogens were recovered from peritoneum, fascia, or
bile in 11 cases. By univariate analysis, a positive culture was significantly
associated with choledochojejunostomy (P=0.0002), previous liver transplantation
(P=0.0002), and previous hepatobiliary surgery (P=0.002). Operative site
infections during the first 2 weeks after transplantation occurred only in cases
with positive intraoperative cultures, and three of the four infections were
caused by the same bacteria detected intraoperatively. Antibiotic susceptibility
of intraoperative isolates was tested in nine cases; infection occurred in two of
three cases in which the isolates were resistant to the systemic antibiotic
prophylaxis and in none of six cases with susceptible isolates. CONCLUSIONS: Our
findings suggest that systemic antibiotic prophylaxis for more than 2 days may be
beneficial in cases with bacterial contamination of the operative site but may
not be necessary in other cases.
PMID- 9645813
TI - Mycophenolate mofetil in renal transplant recipients with cyclosporine-associated
nephrotoxicity: a preliminary report.
AB - BACKGROUND: There is a great concern over cyclosporine (CsA) nephrotoxicity in
renal transplant recipients, and the effects of conversion from CsA to
azathioprine (AZA) remain controversial. Large studies have demonstrated that
mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is
superior to AZA as a posttransplant immunosuppressant. METHODS: Six patients with
isolated biopsy-proven CsA nephrotoxicity were converted from CsA-AZA to MMF.
RESULTS: Mean follow-up was 12+/-2 months. No patient experienced acute
rejection. The mean serum creatinine concentration decreased from 225+/-58 to
159+/-66 micromol/L (P<0.0005). Hyperlipidemia and blood pressure improved after
CsA withdrawal. CONCLUSION: In a selected transplant population with biopsy
proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to
MMF seems to be safe and allows a significant improvement of renal function.
PMID- 9645814
TI - Histologic features of chronic allograft nephropathy revealed by protocol
biopsies in kidney transplant recipients.
AB - BACKGROUND: The aim of the present study was to describe the histologic features
disclosed by protocol kidney transplant biopsies in patients who experienced
neither acute rejection nor acute renal failure during the 2 years after
transplantation. METHODS: We studied 10 recipients of HLA-identical kidneys from
living-related donors and 31 recipients of cadaveric kidneys. They were selected
because, during the 2 years after transplantation, they did not experience
clinical acute or chronic rejection, their renal function was normal and stable,
and they underwent a protocol kidney biopsy at 3 months and at 2 years after
transplantation. RESULTS: Histologic chronic allograft nephropathy was present in
25% of patients at 3 months and in 50% at 2 years, but was absent in the
recipients of HLA-identical kidneys. Histologic worsening was associated with
increased donor age, the presence of asymptomatic grade I acute rejection at 3
months, and an increased cyclosporine trough level. CONCLUSIONS: Protocol
biopsies contribute important information that could be used to improve the
prophylaxis of chronic allograft nephropathy.
PMID- 9645815
TI - Successful long-term kidney-pancreas transplants in diabetic patients with high C
peptide levels.
AB - BACKGROUND: Pancreas transplants are rarely done in type 2 (noninsulin dependent)
diabetic patients. Most researchers believe that in type 2 diabetic patients,
peripheral insulin resistance plays a central role and also is associated with
relative insulin deficiency or an insulin secretory defect. This suggests that in
patients receiving transplants, the new beta cells will be overstimulated,
leading to beta cell "exhaustion" and graft failure. METHODS: Early in our
experience, simultaneous pancreas-kidney transplant candidates were selected
using only clinical criteria for type 1 diabetes, i.e., early onset of diabetes
and rapid onset of insulin use. Pretransplant sera were available for C-peptide
analysis in 70 of 94 of those patients. Forty-four percent (31/70) were African
American (AA). RESULTS: Thirteen patients (12 AA) with a nonfasting C-peptide
level >1.37 ng/ml were identified. In these patients with high C-peptide levels,
pancreas and kidney survival rates were 10O%. The results did not differ
statistically from the low C-peptide group (< or =1.37 ng/ ml). There were no
differences between patient and pancreas-kidney survival rates when the patients
were separated into AA and non-AA groups. The follow-up was 1-89 months, with a
mean of 45.5 months. CONCLUSIONS: Long-term pancreas graft function is attainable
and beta cell "exhaustion" does not occur in patients with high preoperative C
peptide (>1.37 ng/ ml) levels. AA and non-AA patients have equivalent long-term
patient, kidney, and pancreas-kidney graft survival rates.
PMID- 9645816
TI - Increased CD40 ligand gene expression during human renal and murine islet
allograft rejection.
AB - BACKGROUND: The interaction between CD40 and its ligand CD40L is essential for
the development and maintenance of vigorous immunity. We have sought to
determine: (i) whether a heightened level of CD40L transcripts is evident during
acute allograft rejection and (ii) the kinetics of CD40L gene expression during
allograft rejection. METHODS: By using quantitative reverse transcriptase
assisted polymerase chain reaction techniques, we found that heightened CD40L
gene expression is a correlate of acute human renal allograft rejection (P<0.01).
RESULTS: In a murine model of MHC-mismatched islet allografts, our results showed
that CD40L transcripts were rarely detected at day 2 after transplantation, but
were remarkably heightened at day 5 after transplantation. The transcript levels
then steadily increased and peaked at the time of rejection. CONCLUSION: These
data suggest that therapy aimed at blocking the CD40 to CD40L interaction should
be applied during the immediate posttransplant period.
PMID- 9645817
TI - Xenoantibodies to pig endothelium are expressed in germline configuration and
share a conserved immunoglobulin VH gene structure with antibodies to common
infectious agents.
AB - BACKGROUND: The rejection of pig xenografts in humans is initiated by preformed
antibodies that may be related to the natural antibodies that formulate a first
line of defense against infectious agents. Immunoglobulin gene variable domains
encoding the antibodies that react with similar epitopes expressed on
xenoantigens and bacteria may share structurally similar antigen-binding site
configurations. METHODS: We sequenced the VH immunoglobulin genes and germline
progenitors of two rat monoclonal antibodies that recognize pig xenoantigens.
Nucleic and amino acid sequences of these xenoantibodies were compared with
immunoglobulin genes encoding antibodies that react with bacteria or viruses.
RESULTS AND CONCLUSIONS: VH genes encoding rat anti-pig xenoantibodies are
expressed in germline configuration and share structural similarities, including
identical amino acids in key antigenic contact sites that define antibody
canonical structural groups, with antibodies to infectious agents.
PMID- 9645818
TI - HLA class I and class II antibodies: monitoring before and after kidney
transplantation and their clinical relevance.
AB - BACKGROUND: In search of an alternative screening technique, we compared
complement-dependent cytotoxicity (CDC) with PRA-STAT, a commercially available
enzyme-linked immunosorbent assay (ELISA). METHODS: A total of 188 pre- and
posttransplant sera from 50 renal allograft recipients were tested with both
methods. RESULTS: A significant correlation was found between both methods.
Discrepant results could be explained by the fact that PRA-STAT detects both HLA
class I and II antibodies (while CDC with peripheral blood lymphocytes as target
cell detects mainly HLA class I reactivity), by the presence of IgM antibodies
(which are not detected by the IgG-specific ELISA test), and by CDC "false
positive" results due to antibody rejection treatment. The clinical relevance of
antibodies detected by PRA-STAT is suggested by the following. (a) In eight
patients, donor-specific HLA antibodies detected by PRA-STAT (but not seen by
CDC) resulted in severe rejection episodes, which led to graft loss in four
cases. In all but one patient, antibodies were directed against class II or
mixtures of class I and H antigens. Six patients with complications were shown to
have developed de novo antibodies against DQ incompatibilities. (b) Half of the
patients with a positive ELISA test at the moment of crossmatch experienced
complications. Such patients are at a threefold higher risk of suffering from
rejection episodes and/or graft loss than patients who are not sensitized
(P<0.05, Fisher exact test). CONCLUSIONS: Because PRA-STAT is very reproducible,
detects both HLA class I and II antibodies, and is not influenced by rejection
therapy, we consider it an additional tool for pre- and posttransplant monitoring
of kidney allograft recipients.
PMID- 9645819
TI - Pulmonary infection caused by Rhodococcus equi in a kidney and pancreas
transplant recipient: a case report.
PMID- 9645820
TI - Comment on "Persistent long-term changes in lymphocyte subsets induced by
polyclonal antibodies" by Muller et al.
PMID- 9645821
TI - Noninvasive metabolic assessment of human donor livers: metabolite assignment in
31P magnetic resonance spectroscopy.
PMID- 9645822
TI - The importance of reaching preconception targets for glycemic control in diabetic
women.
PMID- 9645823
TI - Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology,
screening, and treatment. off.
AB - Hyperhomocysteinemia has recently been identified as an important risk factor for
atherosclerotic vascular disease. This article reviews homocysteine metabolism,
causes of hyperhomocysteinemia, the pathophysiological findings of this disorder,
and epidemiological studies of homocysteine and vascular disease. Screening for
hyperhomocysteinemia should be considered for patients at high risk for vascular
disease or abnormalities of homocysteine metabolism. For primary prevention of
vascular disease, treatment of patients with homocysteine levels of 14 micromol/L
or higher should be considered. For secondary prevention, treatment of patients
with homocysteine levels of 11 micromol/L or higher should be considered.
Treatment is most conveniently administered as a folic acid supplement (400-1000
microg) and a high-potency multivitamin that contains at least 400 microg of
folate. Higher doses of folic acid and cyanocobalamin supplements may be required
in some patients. Until prospective clinical trial data become available, these
conservative recommendations provide a safe, effective, and evidence-based
approach to the diagnosis, evaluation, and management of patients with
hyperhomocysteinemia.
PMID- 9645824
TI - Klinefelter syndrome.
AB - Klinefelter syndrome is the most common sex chromosome disorder. Affected males
carry an additional X chromosome, which results in male hypogonadism, androgen
deficiency, and impaired spermatogenesis. Some patients may exhibit all of the
classic signs of this disorder, including gynecomastia, small testes, sparse body
hair, tallness, and infertility, whereas others, because of the wide variability
in clinical expression, lack many of these features. Treatment consists of
testosterone replacement therapy to correct the androgen deficiency and to
provide patients with appropriate virilization. This therapy also has positive
effects on mood and self-esteem and has been shown to protect against
osteoporosis, although it will not reverse infertility. Although the diagnosis of
Klinefelter syndrome is now made definitively using chromosomal karyotyping,
revealing in most instances a 47,XXY genotype, the diagnosis also can be made
using a careful history and results of a physical examination, with the hallmark
being small, firm testes. As it affects 1 in 500 male patients and presents with
a variety of clinical features, primary care physicians should be familiar with
this condition.
PMID- 9645825
TI - Echocardiographic predictors of stroke in patients with atrial fibrillation: a
prospective study of 1066 patients from 3 clinical trials.
AB - BACKGROUND: Clinical features that consistently predict ischemic stroke in
patients with nonvalvular atrial fibrillation have been identified, while
echocardiographic risk factors are less well defined. OBJECTIVE: To determine
whether the results of transthoracic echocardiography add independent information
to the clinical risk factors for stroke in patients with atrial fibrillation.
METHODS: Transthoracic echocardiographic findings and clinical features from 1066
patients with atrial fibrillation assigned to placebo or control in 3 randomized
trials (Boston Area Anticoagulation Trial for Atrial Fibrillation, Stroke
Prevention in Atrial Fibrillation I Study, and Veterans Affairs Prevention in
Atrial Fibrillation Study) were correlated with subsequent ischemic stroke by
multivariate analysis. RESULTS: The mean + SD age of patients was 67 +/- 10
years, 78% were men, 55% had a history of hypertension, 19% had a history of
diabetes, 7% had a previous transient ischemic attack or stroke, and 27% had a
history of heart failure. During a mean follow-up of 1.6 years, 78 ischemic
strokes occurred (annual rate, 4.7%). Moderate to severe left ventricular
systolic dysfunction shown via 2-dimensional echocardiography was a strong
independent predictor of stroke (relative risk, 2.5; P<.001) in the 1010 patients
in whom echocardiographic values for left ventricular function were available.
Left atrial diameter by M-mode echocardiography did not predict stroke (relative
risk, 1.02/mm; P = .10). Of 163 patients categorized as low risk based on
clinical features (annual stroke rate, 0.8%; 95% confidence interval, 0.2%-3.0%),
10 had moderate to severe left ventricular dysfunction shown via 2-dimensional
echocardiography and a 9.3% per year risk of stroke (95% confidence interval,
1.3%-66%). Conversely, 728 of the 847 patients at high risk for stroke based on
clinical criteria had normal or mildly abnormal left ventricular function; their
stroke rate was 4.4% (95% confidence interval, 3.4%-5.8%). CONCLUSIONS: Left
ventricular systolic dysfunction shown via 2-dimensional transthoracic
echocardiography independently predicts risk of stroke in patients with atrial
fibrillation. Echocardiography may prove most useful in a small group of patients
who have a low risk of stroke according to clinical factors.
PMID- 9645826
TI - Factors influencing preconception control of glycemia in diabetic women.
AB - BACKGROUND: Although periconceptional glycemic control directly impacts perinatal
outcome for pregestational diabetic women, these women still frequently enter
pregnancy with suboptimal control of glycemia. OBJECTIVES: To determine how
frequently diabetic women enter pregnancy with suboptimal glycemic control and to
identify factors associated with not achieving optimal periconceptual control of
glycemia. PATIENTS AND METHODS: Pregestational diabetic women (n = 55) who
attended the Maternal Fetal Medicine Faculty Practice or the Resident Medical
Complications Obstetric Clinic, Magee Women's Hospital, Pittsburgh, Pa, were
administered a brief questionnaire pertaining to periconceptional education and
control of glycemia. Levels of periconceptional hemoglobin A1c, were measured in
all patients. RESULTS: Sixty-one percent of pregestational diabetic women
presented for prenatal care with suboptimal control of their blood glucose levels
(hemoglobin A1c measurement, >0.08). Of the 55 diabetic women who participated in
the questionnaire, 47 (86%) were under the care of a physician for their
diabetes, 45 (82%) monitored their glucose level at least 3 times per day, 34
(60%) stated that they had been advised to plan a pregnancy, and 29 (53%) stated
that they had planned their pregnancies. Women who had not been advised to
achieve target hemoglobin A1c levels were more likely to enter pregnancy with
suboptimal control of their blood glucose levels (P = .02). Women who experienced
prior complications with pregnancy were significantly more likely to enter
pregnancy with suboptimal control of their blood glucose levels (P = .02).
CONCLUSIONS: Diabetic women frequently enter pregnancy with suboptimal control of
glycemia. Women not advised to achieve target glucose or hemoglobin A1c levels
were more likely to enter pregnancy with suboptimal control of glycemia.
PMID- 9645827
TI - Preinfarction blood pressure and smoking are determinants for a fatal outcome of
myocardial infarction: a prospective analysis from the Finnmark Study.
AB - BACKGROUND: Serum cholesterol levels, blood pressure, and smoking are the classic
coronary risk factors, but what determines whether a myocardial infarction will
be fatal or not? OBJECTIVE: To investigate cardiovascular risk factors that may
influence survival in subjects with coronary heart disease (myocardial infarction
and sudden death). SUBJECTS AND METHODS: All inhabitants aged 35 to 52 years in
Finnmark County, Norway, were invited to a cardiovascular survey in 1974-1975
and/or 1977-1978. Attendance rate was 90.5%. A total of 6995 men and 6320 women
were followed up for 14 years with regard to incident myocardial infarction and
sudden death. Predictors for 28-day case fatality rate after first myocardial
infarction were analyzed. RESULTS: During 186 643 person-years, 635 events among
men and 125 events among women were registered. The case fatality rate was 31.6%
in men and 28.0% in women (P =.50). Among men (women) with baseline systolic
blood pressure lower than 140 mm Hg, the 28-day case fatality rate was 24.5%
(22.6%), among those with systolic blood pressure of 140 through 159 mm Hg, the
case fatality rate was 35.6% (28.2%), and among those with systolic blood
pressure of 160 mm Hg or higher, the case fatality rate was 48.2% (41.7%). Of the
760 subjects with myocardial infarction, 348 died during follow-up. In Cox
regression analysis, systolic blood pressure at baseline was strongly related to
death (relative risk per 15 mm Hg, 1.22; 95% confidence interval, 1.13-1.31).
Daily smoking at baseline (relative risk, 1.40; 95% confidence interval, 1.07
1.85) and age at time of event (relative risk per 5 years, 1.12; 95% confidence
interval, 1.01-1.24) were additional significant risk factors, while total serum
and high-density lipoprotein cholesterol levels were unrelated to survival.
Similar results were obtained with diastolic blood pressure in the model.
CONCLUSIONS: Preinfarction blood pressure was an important predictor of case
fatality rate in myocardial infarction. Daily smoking and age were additional
significant predictors.
PMID- 9645828
TI - Obesity without sleep apnea is associated with daytime sleepiness.
AB - BACKGROUND: Daytime sleepiness and fatigue is a frequent complaint of obese
patients even among those who do not demonstrate sleep apnea. OBJECTIVE: To
assess in the sleep laboratory whether obese patients without sleep apnea are
sleepier during the day compared with healthy controls with normal weight.
METHODS: Our sample consisted of 73 obese patients without sleep apnea, upper
airway resistance syndrome, or hypoventilation syndrome who were consecutively
referred for treatment of their obesity and 45 controls matched for age. All
patients and healthy controls were monitored in the sleep laboratory for 8 hours
at night and at 2 daytime naps, each for 1 hour the following day. RESULTS: Obese
patients compared with controls were sleepier during the day and their nighttime
sleep was disturbed. During both naps, sleep latency, wake time after onset of
sleep, and total wake time were significantly lower, whereas the percentage of
sleep time was significantly higher in obese patients compared with controls. In
contrast, during the nighttime testing, obese patients compared with controls
demonstrated significantly higher wake time after onset of sleep, total wake
time, and lower percentage of sleep time. An analysis of the relation between
nighttime and daytime sleep suggested that daytime sleepiness in obese patients
is a result of a circadian abnormality rather than just being secondary to
nighttime sleep disturbance. CONCLUSIONS: Daytime sleepiness is a morbid
characteristic of obese patients with a potentially significant impact on their
lives and public safety. Daytime sleepiness in individuals with obesity appears
to be related to a metabolic and/or circadian abnormality of the disorder.
PMID- 9645829
TI - Diuretic-based treatment and cardiovascular events in patients with mild renal
dysfunction enrolled in the systolic hypertension in the elderly program.
AB - BACKGROUND: It is expected that the treatment of hypertension in patients with
renal disease decreases the risk of cardiovascular events, but the evidence in
these patients is lacking. OBJECTIVE: To assess the effect of diuretic-based
treatment on cardiovascular events in patients with isolated systolic
hypertension and renal dysfunction. METHODS: A total of 4336 persons aged 60
years and older with systolic blood pressures of 160 mm Hg and higher and
diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive
either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol
(25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years.
The risk of first-occurring cardiovascular events, including stroke, transient
ischemic attack, myocardial infarction, heart failure, coronary artery bypass
surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was
stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6,
101.7-119.3, and 119.4-212.2 micromol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4
mg/dL]). RESULTS: Systolic blood pressure reduction was not affected by baseline
serum creatinine levels. Active treatment did not affect the risk of serum
creatinine levels becoming elevated during follow-up. The risk of hypokalemia
with active treatment decreased significantly with increasing baseline serum
creatinine levels. In the 4 baseline serum creatinine groups, the relative risk
(95% confidence interval) of cardiovascular events developing with active
treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59
(0.38-0.91). The results were similar for the outcomes of stroke or coronary
artery events and in analyses stratified by sex or age. CONCLUSION: Diuretic
based treatment of patients with isolated systolic hypertension prevents the
development of cardiovascular events in older persons with mild renal
dysfunction.
PMID- 9645830
TI - Safely increasing the proportion of patients with community-acquired pneumonia
treated as outpatients: an interventional trial.
AB - BACKGROUND: Patients with community-acquired pneumonia who are at low risk for
short-term mortality can be identified using a validated prediction rule, the
Pneumonia Severity Index. Such patients should be candidates for outpatient
treatment, yet many are hospitalized. OBJECTIVE: To assess a program to safely
increase the proportion of low-risk patients with pneumonia treated at home.
METHODS: The intervention provided physicians with the Pneumonia Severity Index
score and corresponding mortality risk for eligible patients and offered enhanced
visiting nurse services and the antibiotic clarithromycin. Prospectively
enrolled, consecutive low-risk patients with pneumonia presenting to an emergency
department during the intervention period (n = 166) were compared with
consecutive retrospective controls (n = 147) identified during the prior year. A
second group of 208 patients from the study hospital who participated in the
Pneumonia Patient Outcomes Research Team cohort study served as controls for
patient-reported measures of recovery. RESULTS: There were no significant
baseline differences between patients in the intervention and control groups. The
percentage initially treated as outpatients increased from 42% in the control
period to 57% in the intervention period (36% relative increase; 95% confidence
interval, 8%-72%; P = .01). However, more outpatients during the intervention
period were subsequently admitted to the study hospital (9% vs 0%). When any
admission to the study hospital within 4 weeks of presentation was considered,
there was a trend toward more patients receiving all their care as outpatients in
the intervention group (42% vs 52%; 25% relative increase; 95% confidence
interval -2% to 59%; P = .07). No patient in the intervention group died in the 4
week follow-up period. Symptom resolution and functional status were not
diminished. Satisfaction with overall care was similar, but patients treated in
the outpatient setting during the intervention were less frequently satisfied
with the initial treatment location than comparable control patients (71% vs 90%;
P = .04). CONCLUSIONS: Use of a risk-based algorithm coupled with enhanced
outpatient services effectively identified low-risk patients with community
acquired pneumonia in the emergency department and safely increased the
proportion initially treated as outpatients. Outpatients in the intervention
group were more likely to be subsequently admitted than were controls, lessening
the net impact of the intervention.
PMID- 9645831
TI - Physical examination and chronic lower-extremity ischemia: a critical review.
AB - OBJECTIVE: To determine the clinical utility of physical examination in patients
with suspected chronic ischemia of the lower extremities. DATA SOURCES: MEDLINE
search (January 1966 to January 1997), personal files, and bibliographies of
textbooks on physical diagnosis, surgery, and vascular surgery. STUDY SELECTION:
Both authors independently graded the studies as level 1, 2, or 3, according to
predetermined criteria. Criteria deemed essential for analysis of sensitivity,
specificity, and likelihood ratios were (1) clear definition of study population,
(2) clear definition of physical examination maneuver, and (3) use of an
acceptable criterion standard test for comparison. RESULTS: The following
positive findings help clinicians diagnose the presence of peripheral arterial
disease: abnormal pedal pulses, a unilaterally cool extremity, a prolonged venous
filling time, and a femoral bruit. Other physical signs help determine the extent
and distribution of vascular disease, including an abnormal femoral pulse, lower
extremity bruits, warm knees, and the Buerger test. The capillary refill test and
the findings of foot discoloration, atrophic skin, and hairless extremities are
unhelpful in diagnostic decisions. Mathematical formulas, derived from 2 studies
using multivariate analysis, allow clinicians to estimate the probability of
peripheral arterial disease in their patients. CONCLUSION: Certain aspects of the
physical examination help clinicians make accurate judgments about the presence
of peripheral arterial disease and its distribution.
PMID- 9645832
TI - Globus sensation: pharyngoesophageal function, psychometric and psychiatric
findings, and follow-up in 88 patients.
AB - BACKGROUND: The globus sensation has been widely regarded as psychogenic, but
organic disorders were found to be etiologically significant. OBJECTIVE: To
investigate the structural, functional, psychological, and psychiatric factors
possibly eliciting the globus sensation and influencing its course. METHODS:
Eighty-eight patients, 67 women and 21 men (aged 22-71 years), referred to 2
tertiary care centers underwent history taking, otolaryngological examination,
pharyngoesophageal videofluoroscopy and manometry, psychosocial evaluation,
psychometric tests, psychiatric interview, and when indicated,
esophagogastroduodenoscopy, esophageal bolus transport, gastroesophageal reflux,
and gastric emptying studies. According to revealed disorders, therapy was
initiated, and the outcome was studied. RESULTS: Only 15 patients had normal
pharyngoesophageal function; of these 15, 6 had chronic tonsillitis or
pharyngitis, 3 had thyroid adenomata, 4 had cervical spondylosis, and 1 each had
dry oropharyngeal mucosa and chronic bronchitis. Of the other 73 patients, 2 had
pharyngeal dysfunction, 24 had achalasia, 1 had diffuse esophageal spasms, 3 had
"nutcracker esophagus," 30 had nonspecific esophageal motor disorders, and 13 had
gastroesophageal reflux. Psychometry revealed no more anxiety and depression than
in general medical outpatients. Of 58 patients interviewed, 37 met criteria for
psychiatric disorders. Psychometric scores and psychiatric characteristics were
unrelated to the sensation's course. Therapy was recommended, but only 26
patients were treated accordingly; 22 received nonspecific treatment. Follow-up 3
to 59 months later revealed that the sensation had vanished in 13 patients who
had received specific treatment, 5 who had received nonspecific treatment, and 6
who had received no treatment; it was alleviated in 10 who had received specific
treatment, 13 who had received nonspecific treatment, and 9 who had received no
treatment; and it was unchanged in 3 who had received specific treatment, 5 who
had received nonspecific treatment, and 23 patients who had received no
treatment. CONCLUSIONS: Pharyngoesophageal disorders may be sensed only vaguely,
inducing the globus sensation. Psychological and psychiatric characteristics
could be relevant to the discomfort experienced but are unlikely to be
etiologically significant.
PMID- 9645833
TI - What appears to be cancer.
AB - We describe a case of multiple hepatic pyogenic abscesses with an unusual
presentation. The typical signs and symptoms of fever and pain in the right upper
quadrant were absent. Instead, the chief complaint was muscle weakness and
myalgias accompanied by weight loss. Findings from an ultrasonogram of the
abdomen revealed multiple hepatic lesions consistent with metastases. Hence, the
initial presumptive diagnosis was metastatic malignancy with unknown primary
tumor. It was only when purulent material was unexpectedly encountered when a
needle biopsy was performed that the true diagnosis of pyogenic liver abscess was
recognized. While liver abscess is rare, it should not be forgotten in the
differential diagnosis for multiple hepatic lesions seen on imaging studies.
PMID- 9645834
TI - Pseudo-Meigs syndrome with elevated CA 125 levels.
PMID- 9645835
TI - Sublingual nifedipine-induced anaphylaxis.
PMID- 9645836
TI - Proton irradiation for non-small cell lung cancer.
PMID- 9645837
TI - Antithymocyte globulin-induced adult respiratory distress syndrome.
PMID- 9645838
TI - Esophageal stenosis and Graves disease in brittle type 1 diabetes mellitus.
PMID- 9645839
TI - Pseudopheochromocytoma: an unrecognized cancer-associated syndrome?
PMID- 9645840
TI - A method for the isolation of tegument syncytium mitochondria from Taenia
crassiceps cysticerci and partial characterization of their aerobic metabolism.
AB - Heterogeneous populations of mitochondria have been described in helminths.
Mitochondria from different tissues have been isolated in adult organisms.
However, in larvae, due to their small size, isolation from tissues has not been
feasible. A method for the isolation of tegumental mitochondria from the larval
stage of Taenia crassiceps is described. After solubilization of the plasma
membrane with saponin, tegumental mitochondria were purified by a simple and
rapid protocol of differential centrifugation, which allowed the retention of
suitable quantities of well-preserved mitochondria, as judged by biochemical and
ultrastructural parameters. Respiratory activity evoked by exogenous NADH was
negligible, but its oxidation increased several-fold after sonication of intact
mitochondria. Other substrates, e.g., succinate and malate-glutamate, were
oxidized at high rate, leading to the formation of a H+ gradient across the inner
mitochondrial membrane, which, in turn, supported oxidative phosphorylation.
These results indicate that tegumental mitochondria carry out aerobic metabolism.
PMID- 9645842
TI - Gastrointestinal helminths of loggerhead turtles (Caretta caretta) from the
western Mediterranean: constraints on community structure.
AB - Richness and composition of gastrointestinal helminth communities of 54
loggerhead turtles, Caretta caretta, from the western Mediterranean were
interpreted from patterns of helminth exchange at 2 host taxonomic scales:
exchange between marine turtles and other marine hosts and exchange within
turtles. We predicted exchange of the former to be unimportant ecologically and
evolutionarily because of the host phylogenetic distance. The absence of records
of successful exchange at this host taxonomic scale confirmed that host
physiological barriers seem to prevent contemporary parasite transfer between
marine turtles and other sympatric hosts. Marine turtles also seem to exhibit an
evolutionary association with their parasites largely independent from that of
other marine hosts. Therefore, the composition of gastrointestinal helminth
communities of marine turtles is predictably restricted to digeneans, nematodes,
and aspidogastreans specific to these reptiles. At the scale of host species,
helminth exchange among marine turtle species was expected to be significant.
This was suggested by reports indicating a high proportion of parasites common to
all sea turtle species. Mediterranean C. caretta harbored only 4 digenean species
typical of marine turtles, and immature individuals of 1 digenean species
accidentally acquired. Further, no relevant parasite exchange with other marine
turtles was expected to occur because C. caretta is the only sea turtle species
abundant in the western Mediterranean. Therefore, a predictable composition
coupled with low species richness in infracommunities might be accounted for
partly by constraints on parasite acquisition at both host scales. Host factors
limiting parasite recruitment (mainly ectothermy and a wandering behavior) may
also contribute to depauperate and isolationist infracommunities.
PMID- 9645841
TI - Increased excretion of aromatic amino acid catabolites in animals infected with
Trypanosoma brucei evansi.
AB - Aromatic amino acid catabolism by Trypanosoma brucei evansi was investigated in
vivo using C3HeB/FeJ mice. The major catabolites detected by gas chromatography
in the urines of infected animals were phenylpyruvic acid, 4-hydroxyphenylpyruvic
acid, and indole-3-pyruvic acid. Identity of each compound was confirmed by gas
chromatography-mass spectrometry. Concentrations of catabolites in urine of
infected mice were correlated with parasitemia and returned to normal following
suramin treatment. Other aromatic amino acid metabolites, including indole-3
acetic acid, indole-3-lactic acid, and 4-hydroxyphenyllactic acid, were detected
in urine from infected animals by gas chromatography mass spectrometry, although
quantities were too low to be quantified reproducibly. Both phenylpyruvic acid
and 4-hydroxyphenylpyruvic acid were also detected in urine of dogs and donkeys
experimentally infected in Egypt with a recent field isolate of T. b. evansi.
Tryptophan metabolites could not be assayed in dog and urine samples because
formalin, which degraded the indole acids, had to be added before the samples
could be imported into the U.S. Finally, concentrations of urinary catabolites
during infection were correlated with the tyrosine aminotransferase activity in
infected mouse sera.
PMID- 9645843
TI - Ascaris lumbricoides intensity in relation to environmental, socioeconomic, and
behavioral determinants of exposure to infection in children from southeast
Madagascar.
AB - Ascaris lumbricoides worm counts were examined as the outcome products of
exposure proxy variables. A survey of 663 children, 4-10 yr old, living in
southeastern Madagascar revealed prevalences of 93% for A. lumbricoides, 55% for
Trichuris trichiura, and 27% for hookworm. Worm expulsions were conducted on 428
of these children; the data revealed an overdispersed distribution of A.
lumbricoides, with an arithmetic mean of 19.2 worms per child. A concurrent
socioeconomic household survey was conducted by visitation and interview.
Exposure to infection was assessed by environmental, demographic, behavioral, and
socioeconomic indicators. Ascaris lumbricoides aggregations were associated with
gender, housing style, ethnicity, and agricultural factors. The results suggest
that exposure and infection are ubiquitous in this child population, and that A.
lumbricoides intensity is influenced by gender-related behavioral and
environmental factors that contribute to exposure.
PMID- 9645844
TI - Comparison of three estimators of species richness in parasite component
communities.
AB - Comparisons of species richness between parasite component communities are often
confounded by uneven sampling effort and the possibility that rare species have
been missed from some component communities. The use of nonparametric estimators
of species richness could potentially alleviate this problem by allowing the
number of missing species to be extrapolated from the observed data. The
performance of 3 estimators and their sensitivity to true species richness and
the frequency of rare species, i.e., species with low prevalence, were tested
using computer-simulated parasite communities. When the number of hosts examined
in a sample is large, the observed species richness is an accurate estimate of
true richness; no extrapolation is necessary even when rare species make up a
large part of the community. At small sample sizes, observed species richness is
a poor underestimate of true richness. The jackknife estimator and Chao's
estimator both improve the estimate of species richness, but they are imprecise
and can seriously overshoot the true richness value when the community includes
many rare species. The bootstrap estimator. on the other hand, gives a better
estimate than observed richness. Bootstrap estimates are also less variable and
less likely to overestimate true richness, independently of how frequent rare
species are in the community. This estimator provides a better, but conservative,
estimate of true richness than observed richness and should be used to correct
for inadequate host sampling. Data from natural communities suggest that the use
of richness estimators is often justified, and that many parasite species may
regularly escape detection.
PMID- 9645845
TI - Host-mediated site segregation of ectoparasites: an individual-based simulation
study.
AB - Site segregation of coexisting ectoparasite species may result either from a
direct interaction such as resource competition between them or from a host
mediated interaction. Here we present an individual-based model for the
coevolution of 1 host and 2 parasite species to study this latter hypothesis.
Parasite species are generalists at the start of the simulation and develop site
specificities under the following assumptions. Parasite populations are not
subject to resource limitations but are limited directly by host defense as
predation. Hosts have 2 sites that need different defensive abilities to reduce
their parasite burden. Parasites need to exhibit different evasive abilities to
survive on different sites. Host grooming selects parasites for an increasing
capability for evasion, whereas parasites select hosts for an increasing
efficiency of grooming. Two trade-offs are incorporated into the model: one
between host defensive abilities on the 2 sites, and another between parasite
evasive abilities on the 2 sites. We conclude that, under these assumptions, the
optimization of host defense and parasite evasion strategies may select
ectoparasites for site segregation and this may stabilize the coexistence of
parasite species.
PMID- 9645846
TI - Lyme disease spirochetes in ticks from northeastern China.
AB - During May 1996, field surveys on Lyme disease spirochetes were conducted in
Beijing, Shenyang, Fushun, and Inner Mongolia in northeastern China. The ticks
collected consisted of 3 genera and 12 species. Of these, Ixodes persulcatus was
dominant in sun-exposed vegetation in forests in Inner Mongolia; 57 Borrelia
strains (55/123 unfed adults and 2/5 immature stages fed on a rodent) were
obtained from this tick by BSK culture. Additionally, 2/2 Apodemus peninsulae
were positive. Ixodes nipponensis, Ixodes pavlovskyi, Haemaphysalis douglasi, and
Haemaphysalis megaspinosa, newly recorded in China, and other Haemaphysalis spp.
were all negative for Borrelia. Based on a polymerase chain reaction restriction
fragment length polymorphism analysis of the 45 strains successfully subcultured,
these were classified as 29 Borrelia garinii and 16 Borrelia afelii. These
strains seemed to be more closely related to Japanese strains in genetic features
than to those from Europe. The result of sodium dodecyl sulfate-polyacrylamide
gel electrophoresis suggested more diversity in both genospecies, but Borrelia
burgdorferi sensu stricto was not found.
PMID- 9645847
TI - Ultrastructure of the oocysts, sporocysts, and sporozoites of Toxoplasma gondii.
AB - Transmission and scanning electron microscopy were used to study the
ultrastructure of the oocysts, sporocysts, and sporozoites of the VEG strain of
Toxoplasma gondii and to compare the ultrastructure of sporozoites with
tachyzoites (from the peritoneum of mice) and bradyzoites (from brain tissue
cysts in mice). Oocysts were surrounded by a thin veil of finely reticulate
material. The oocyst wall consisted of 3 layers and contained a previously
unknown disc-shaped micropyle that appeared as a depression in the oocyst wall.
The sporocyst contained 4 sporozoites and a residuum of lipid and amylopectin
granules. The sporocyst wall was 3-layered with the innermost layer consisting of
4 curved plates held together at sutures by an interposed strip. Exposure to
excysting fluid caused the interposed strip to separate from the curved plates,
which curled inward releasing the sporozoites. Sporozoites had a posteriorly
located nucleus and all the organelles typical for coccidian zoites. Sporozoites,
tachyzoites, and bradyzoites had similar numbers of rhoptries but differed in the
numbers and sizes of micronemes, dense granules, amylopectin granules, and lipid
bodies.
PMID- 9645848
TI - Demonstration of Taenia crassiceps cysteine proteinase activity in tegumentary
lysosome-like vesicles.
AB - Larval stages of Taenia species survive for prolonged periods in the tissues of
their intermediate hosts. Other groups have demonstrated that host
immunoglobulins are taken up by the cysticerci by adsorptive endocytosis,
degraded, and the amino acids incorporated into parasite proteins. We have shown
that a 43-kDa cysteine proteinase is the major parasite enzyme that degrades
immunoglobulin in vitro. To localize this enzyme in situ, Taenia crassiceps
cysticerci were incubated with the peptide substrate Z-Phe-Arg
methoxynaphthylamide. Free methoxynaphthylamide was coupled to p-rosanilin and
osmium and visualized by transmission electron microscopy. Initial studies of
cysticerci incubated without substrate confirmed the normal microanatomy and
absence of significant host inflammation. In comparison to controls with no
substrate, sections of cysticerci incubated with substrate revealed electron
dense deposits in round vesicles. The vesicles were found primarily within the
tegumentary cytons and internuncial processes, a location similar to that
described for vesicles associated with adsorptive endocytosis. There were
proportionately more endocytotic vesicles and electron-dense vesicles in smaller
cysticerci than larger ones. Formation of electron-dense deposits was inhibited
by heat and partially inhibited by the cysteine proteinase inhibitor E-64. These
data are consistent with localization of the cysteine proteinase activity to
lysosome-like vesicles.
PMID- 9645849
TI - Taenia crassiceps cysticercosis: humoral immune response and protection elicited
by DNA immunization.
AB - The purpose of this study was to evaluate DNA vaccination in cysticercosis
prevention by using a Taenia crassiceps cDNA of a recombinant antigen (KETc7)
that has been reported as protective against murine cysticercosis. The KETc7 cDNA
was cloned into the pcDNA3 plasmid alone or with the betaglycan signal peptide
sequence (pTc-7 and pTc-sp7, respectively). Positive expression of the pTc-sp7
product was confirmed by transfection of C33 cells and immunofluorescence using
sera of mice infected with T. crassiceps. Immunization of mice with 3 injections
of pTc-sp7 DNA at the higher dose (200 microg) was the most effective to induce
antibody with or without bupivacaine. Immunization with pTc-sp7 induced
protection against challenge with T. crassiceps cysticerci as successfully as
previously observed with the KETc7 recombinant protein. Antibodies elicited by
DNA immunization with pTc-sp7 specifically reacted with the native protein of 56
kDa previously reported, which is immunolocalized in the tegument of T.
crassiceps cysticerci. The 56-kDa antigen is also present in Taenia solium
oncospheres, cysticerci, and adult tissue. The protection induced in DNA
immunized mice and the observation that the injected plasmid remains as an
episomic form within muscle cells, encouraged us to continue testing this
procedure to prevent T. solium cysticercosis.
PMID- 9645851
TI - The specificity of behavioral fever in the cricket Acheta domesticus.
AB - When infected, some insects can raise their body temperature by moving to warmer
areas. This behavioral fever response can help the host overcome infection.
However, not all parasites and pathogens are equally susceptible to increases in
host temperature. Elevating the temperature of the cricket Acheta domesticus from
room temperature (22 C) to 33 C did not reduce the survival of parasitoid flies
or reduce the number of gregarine gut protozoans, and crickets infested with
these parasites showed no increase in their temperature preference. Warmer
temperatures (33 C) did not increase the survival of crickets infected with the
bacterium Serratia marcescens, and infected crickets did not prefer warmer
temperatures. However crickets infected with the intracellular parasite
Rickettsiella grylli were more likely to survive when the host was exposed to
warmer temperatures. Crickets infected with R. grylli increased their preferred
temperature from 26 C to 32 C. In A. domesticus, behavioral fever may be a
specific response induced by relatively few pathogens and parasites. Behavioral
fever in insects may differ in this respect from fever in mammals that can be
elicited by a wide variety of parasites and pathogens.
PMID- 9645850
TI - Demonstration of shared carbohydrate epitopes in intestinal proteins of some
bovine gastrointestinal nematodes.
AB - The presence of shared carbohydrate intestinal epitopes in bovine
gastrointestinal nematodes was demonstrated. Proteins were extracted from the
intestinal tissue of a laboratory strain of adult Haemonchus placei and used to
produce monoclonal antibodies (mAb). Analysis of this detergent extract by sodium
dodecyl sulfate-polyacrylamide gel electrophoresis revealed 7-9 bands ranging
from approximately 39 to 298 kDa. The mAbs reacted with periodate-sensitive
epitopes and, in western blots, recognized high molecular weight protein bands
(approximately 111-298 kDa). Immunohistochemical studies with the mAbs verified
the intestinal location of the epitope(s) in the laboratory strain as well as in
a recent field isolate of H. placei. Epitope(s) were conserved among species
examined within the Trichostrongyloidea (Ostertagia ostertagi, Cooperia punctata,
Haemonchus placei, and Haemonchus contortus), semiconserved among species within
the Strongyloidea (present in Oesophagostomum radiatum, absent in Oesophagostomum
venulosum), and absent in the only species examined in the Ancylostomatoidea
(Bunostomum phlebotomum).
PMID- 9645852
TI - Structure of Leptorhynchoides thecatus and Pomphorhynchus bulbocolli
(Acanthocephala) eggs in habitat partitioning and transmission.
AB - The role of egg structure in transmission and habitat use of Leptorhynchoides
thecatus and Pomphorhynchus bulbocolli (Acanthocephala) was investigated. During
storage in tap water at 4 C, the outer membrane of L. thecatus eggs was lost,
releasing ribbonlike filaments of the fibrillar coat. After similar storage, the
outer membrane and fibrillar coat of P. bulbocolli eggs remained intact. Eggs of
L. thecatus entangled in algae, whereas those of P. bulbocolli settled to the
substratum. Leptorhynchoides thecatus infections in amphipod intermediate hosts
were significantly more prevalent and dense when eggs were allowed to entangle
than when they were not. Prevalence and relative density of P. bulbocolli
infections in amphipods were not significantly different between trials in which
entanglement was possible and those in which it was not. These results indicate
that although the same species of amphipod, Hyalella azteca, is the intermediate
host for both acanthocephalan species, mechanisms of transmission differ.
Differences in fibrillar coats result in segregation of the environment in a
manner that affects transmission and occurrence in intermediate hosts.
PMID- 9645853
TI - First record of trypanosomes in Tasmanian bandicoots.
AB - Trypanosomes were observed in 38% of blood smears from southern brown bandicoots
(Isoodon obesulus) and in 10% of blood smears from eastern barred bandicoots
(Perameles gunnii). This is the first record of such hemoparasites in Tasmanian
marsupials. There appeared to be a statistically significant size difference
between trypanosomes found in the 2 bandicoot species, suggesting the possibility
of 2 distinct species of parasite. There appears to be a distinction between the
trypanosomes found in our temperate Isoodon species and the tropical bandicoot.
Isoodon macrurus. The use of the microhematocrit method provided an effective
means for concentrating trypanosomes, whereas image analysis was a more effective
method than the ocular micrometer for obtaining accurate measurements.
PMID- 9645854
TI - Vector ability of mosquitoes for isolates of Plasmodium elongatum from raptors in
Florida.
AB - Three isolates of Plasmodium elongatum were obtained from 3 species of raptors
(red-tailed hawk [Buteo jamaicensis], bald eagle [Haliaeetus leucocephalus], and
eastern screech owl [Otus asio]) from Florida using isodiagnostic techniques in
Pekin ducks (Anas platyrhynchos). Six to 10 species of mosquitoes were tested for
susceptibility to these 3 isolates. Complete development of the sporogonic cycle
of the 3 isolates of P. elongatum occurred in 3 species of mosquitoes, Culex
nigripalpus, Culex restuans, and Culex salinarius. The pattern of susceptibility
was similar among the 3 isolates of P. elongatum in Cx. nigripalpus. Culex
restuans and Cx. salinarius were significantly more susceptible than Cx.
nigripalpus to the 3 isolates of P. elongatum tested. Culex nigripalpus
transmitted all 3 isolates of P. elongatum from duck to duck both by bite and
after intraperitoneal injection of sporozoites. Infections of the 2 isolates
tested occurred in ducks after intraperitoneal injection of sporozoites from Cx.
restuans and Cx. salinarius. The results suggest that these 3 Culex species are
potential vectors of P. elongatum from raptors in Florida.
PMID- 9645855
TI - Studies on infections with two strains of Plasmodium inui from Taiwan in rhesus
monkeys and different anopheline mosquitoes.
AB - Rhesus monkeys infected with the Taiwan strains of Plasmodium inui could be
appropriate models for understanding host-parasite relationships during long-term
chronic infection. Two strains of P. inui originally from Taiwan were studied in
rhesus monkeys and different anopheline mosquitoes. Maximum parasite counts for
13 intact animals infected with the Taiwan I strain ranged from 22,215 to
760,000/microl (median maximum parasite count = 242,800/microl). Following
splenectomy, the maximum parasite count for the 9 animals ranged from 160,000 to
2,360,000/microl (median = 1,160,000/microl). Sporozoite transmission was
demonstrated via the bites of infected Anopheles dirus mosquitoes and by the
intravenous inoculation of sporozoites harvested from the guts of infected
Anopheles maculatus. Prepatent periods were 12 and 20 days, respectively. With
monkeys infected with the Taiwan II strain, the parasite counts when intact were
from 40,882 to 223,686/microl. After splenectomy, maximum parasite counts ranged
from 96,750 to 1,960,000/microl (median maximum parasite count for 8
splenectomized animals = 840,000/microl). Two transmissions were obtained via the
bites of infected An. dirus mosquitoes; prepatent periods were 10 days. Limited
studies with progressively increasing doses of pyrimethamine resulted in
parasites more resistant to treatment.
PMID- 9645856
TI - Respiratory burst assay of head kidney macrophages of ayu, Plecoglossus
altivelis, stimulated with Glugea plecoglossi (Protozoa: Microspora) spores.
AB - The respiratory burst assay was conducted using the nitroblue tetrazolium
reduction method and horseradish peroxidase method to investigate the events when
ayu head kidney macrophages phagocytize fresh and formalin-killed Glugea
plecoglossi spores. The production of O2 against G. plecoglossi spores was
negligible compared to zymosan (P < 0.01). Zymosan-induced O2 production was
markedly inhibited by adding G. plecoglossi spores simultaneously (P < 0.01).
This phenomenon was dose dependent, and killed spores were less inhibitory than
fresh spores. The production of H2O2 was drastically increased when G.
plecoglossi spores were added (P < 0.01), and most spores were phagocytized. From
these results, it is suggested that G. plecoglossi spores modulate the host's
phagocytic response to establish infection.
PMID- 9645857
TI - Filariasis and erisipela in Santo Domingo.
AB - This study examined acute-convalescent changes in diagnostic anti-streptococcal
antibodies by the anti-streptolysin O (ASO) and anti-DNAase B (ADAB) tests among
patients (n 28) with lymphedema and recurrent erisipela of the lower limb,
comparing them with endemic normal control residents (n=25). The study was based
in Villa Francisca, an urban focus of Bancroftian filariasis in eastern Santo
Domingo, capital of the Dominican Republic. The acute signs and symptoms of
erisipela were consistent with a diagnosis of bacterial cellulitis. The ASO test
was especially successful at demonstrating a rise in mean titer during
convalescence, whereas the ADAB produced about the same frequency of significant
increases (0.2 log titer) as did the ASO. When subjects were scored as responders
if mounting a minimal titer increase by either test, patients were found more
frequently positive than were controls (chi2=5.3, P=0.02). About half (54%) of
all patients mounted at least a minimal antibody increase. Filaria-specific IgG4
antibodies were absent from all sera of 20 residents of a nonendemic Dominican
mountain town but appeared in about two-thirds of the sampled residents of the
endemic barrio. Notably however, levels did not change between the acute phase
and convalescence. These findings are consistent with the hypothesis that
recurrent streptococcal invasion of the lymphatics may be a significant factor
triggering or amplifying lymphedema and elephantiasis in patients with chronic
filariasis.
PMID- 9645858
TI - Three new Sarcocystis species, Sarcocystis giraffae, S. klaseriensis, and S.
camelopardalis (Protozoa: Sarcocystidae) from the giraffe (Giraffa
camelopardalis) in South Africa.
AB - Three new Sarcocystis species recovered from muscle fibers of the skeletal
musculature of a giraffe in South Africa are described based on light and
electron microscopy. Sarcocystis giraffae n. sp. formed slim macrocysts with a
parasite-induced connective tissue encapsulation of the host muscle fiber in
which the plasma membrane of the latter remained unaltered. The sarcocyst wall
represented a new ultrastructural type that is characterized by fingerlike villar
protrusions with a hairlike projection at the tip, containing microtubules
penetrating the ground substance. Sarcocystis klaseriensis n. sp. formed small
filiform microcysts with kinked finger-shaped villar protrusions of the wall,
containing scattered microtubules or filaments, and represented another new
ultrastructural type. Sarcocystis camelopardalis n. sp. formed small filiform
microcysts with straplike villar protrusions of the wall, containing chainlike
osmiophilic structures, and represented again a new ultrastructural type.
PMID- 9645859
TI - Subulura saloumensis n. sp. (Nematoda, Subuluroidea) from four species of rodents
in Senegal.
AB - A new species of the genus Subulura is described from 4 new rodent hosts:
Arvicanthis niloticus, Mastomys erythroleucus, Mastomys huberti, and Tatera
gambiana. Subulura saloumensis n. sp. differs from the congeneric species by the
morphology of its head. the absence of buccal lobes, the length of right and left
spicules, the absence of caudal alae, and the existence of a caudal papillae with
a sensorial bristle. The latter, which we observe for the first time in specimens
gathered from M. huberti, has never previously been described in a species of the
genus Subulura.
PMID- 9645860
TI - Echinocephalus janzeni n. sp. (Nematoda: Gnathostomatidae) in Himantura pacifica
(Chondrichthyes: Myliobatiformes) from the Pacific coast of Costa Rica and
Mexico, with historical biogeographic analysis of the genus.
AB - Echinocephalus janzeni n. sp. in the stingray, Himantura pacifica, is described
from the eastern Pacific Ocean off the coasts of Costa Rica and southern Mexico.
On the basis of the presence of 6 postanal caudal papillae, and modified annules
anterior to the caudal alae in males, E. janzeni is most similar to
Echinocephalus daileyi and Echinocephalus diazi. Specimens of E. janzeni are
distinguished from those of E. daileyi by bilobed caudal alae and long cervical
sacs that extend up to 65% of the length of the esophagus; E. janzeni is
differentiated from E. diazi by the number of rows of cephalic spines (30-38 vs.
26-27), arrangement of the postanal caudal papillae, 3 rather than 2 preanal
papillae, relative position and distance between the anus and vulva (395-460
microm vs. 70 microm), the digitiform female tail with a terminal cuticular fold,
and the length of the female tail (450-480 microm vs. 270 microm). Cladistic
analysis of the 10 Echinocephalus spp. resulted in a single most parsimonious
tree (consistency index=0.893) and placed E. janzeni in a highly derived subclade
where E. daileyi is the sister species of E. diazi + E. janzeni. Historical
biogeographic analysis of hosts and parasites provides support for origins in the
Pacific rather than the Atlantic for the potamotrygonid stingrays.
PMID- 9645861
TI - Reevaluation of Physaloptera bispiculata (Nematoda: Spiruroidaea) by light and
scanning electron microscopy.
AB - This study was undertaken to clarify several aspects of morphological and
taxonomic characters of Physaloptera bispiculata Vaz and Pereira, 1935, a
parasite of the water rat, Nectomys squamipes. The cephalic structures (including
lips, papillae, teeth, amphids, and porous areas) and details of the posterior
end of male and female adult worms were examined by scanning electron microscopy,
leading to the addition of new taxonomic characters for this species. We consider
P. bispiculata a valid species, based on a comparative analysis of the specific
characters for P. bispiculata and P. getula Seurat, 1917, including the
morphology and morphometry of body structures as well as number and disposition
of caudal papillae of the males.
PMID- 9645862
TI - Two new Huffmanela species, H. japonica n. sp. and H. shikokuensis n. sp.
(Nematoda: Trichosomoididae), from marine fishes in Japan.
AB - Two new species of trichuroid nematodes. Huffmanela japonica n. sp. and
Huffmanela shikokuensis n. sp., are established on the basis of their egg
morphology and biological characters; the eggs of both species occur in the
musculature of marine fishes from the Inland Sea of Japan. The dark-shelled eggs
of H. japonica are found locally in masses ("black spots") in the flesh of
Upeneus bensasi (Temminck et Schlegel) (Mullidae, Perciformes) and are
characterized mainly by their shape and size (58-69 x 26-30 microm), an aspinose
superficial transparent envelope enclosing the egg proper, relatively small polar
plugs, and by their thick egg wall (4-5 microm). The eggs of H. shikokuensis are
also dark-colored and are found evenly distributed in the musculature of
Stephanolepis cirrhifer (Temminck et Schlegel) (Monacanthidae,
Tetraodontiformes); they are characterized mainly by their shape and size (78-90
X 36-45 microm), by a very thin and aspinose superficial transparent envelope,
large polar plugs, and relatively thin egg wall (3 microm). Histological sections
of the host's infected musculature showed the presence of H. shikokuensis
nematodes inside the muscle cells and in the intercellular spaces. A key to
Huffmanela species based on egg morphology is provided.
PMID- 9645863
TI - Redescription of Hapalotrema mistroides (Monticelli, 1896) and Hapalotrema
synorchis Luhman, 1935 (Digenea: Spirorchidae), with comments on other species in
the genus.
AB - Hapalotrema mistroides (Monticelli, 1896) Stiles and Hassall, 1908 and
Hapalotrema synorchis Luhman, 1935 are redescribed using specimens from the
loggerhead turtle. Caretta caretta (L.). The redescription of H. mistroides is
based on specimens collected by Looss and described as Hapalotrema constrictum
Leared, 1862 and renamed Hapalotrema loossi Price, 1934, which is now considered
a junior synonym of H. mistroides. Hapalotrema orientalis Takeuti, 1942 is
considered a junior synonym of Hapalotrema synorchis. The redescriptions are
consistent with the originals but provide an unreported range of variation while
adding new information about the reproductive systems. Reexamination of
Hapalotrema dorsopora Dailey, Fast, and Balazs, 1993 confirms the presence of a
reproductive system typical for the genus and the absence of a dorsal genital
pore; therefore, H. dorsopora is reduced to a junior synonym of Hapalotrema
mehrai Rao, 1976. Four valid species of Hapalotrema are recognized: H.
mistroides. H. synorchis, H. postorchis, and H. mehrai, and a key to the species
is provided.
PMID- 9645864
TI - Characterization of trypanosomes from the subgenus Schizotrypanum isolated from
bats, Eptesicus sp. (Chiroptera: Vespertilionidae), captured in Florianopolis,
Santa Catarina State, Brazil.
AB - Seven Trypanosoma spp. isolates obtained from bats (Eptesicus sp.) were
characterized using experimental infection in mice, triatomines, and culicines;
complement lysis; indirect fluorescence assays; as well as isoenzyme and random
amplified polymorphic DNA (RAPD) profiles. The Trypanosoma sp. isolates were
compared with Trypanosoma cruzi, Trypanosoma rangeli. and 2 other bat
trypanosomes species, Trypanosoma vespertilionis and Trypanosoma hastatus.
Trypanosoma sp. isolates were different from the other species in all
experiments, except in complement lysis. Experimental infection of triatomines
and culicines with Trypanosoma sp. proved to be transitory. These parasites were
noninfective for both normal and immunosuppressed mice. Isoenzyme and RAPD
profiles obtained for Trypanosoma sp. were quite distinct from T. cruzi and T.
rangeli and closely related to T. vespertilionis and T. hastatus. No cross
reaction was observed between sera from mice infected with Trypanosoma sp. and
the other trypanosomatids and vice-versa. Trypanosoma sp. induced no protection
against T. cruzi infection in mice. The very low, or nonsimilarity between
Trypanosoma sp. isolates and the other species used in this study suggests that
they might be members of a distinct bat trypanosome species. However, further
studies should be done to prove their affinities with Trypanosoma cruzi
marinkellei, another trypanosome species from bats.
PMID- 9645865
TI - Trypanosoma cruzi tubulin eliminated in the urine of the infected host.
AB - In previous studies we have identified and characterized an 80-kDa Trypanosoma
cruzi urinary antigen (UAg) eliminated during acute infection. Polyclonal
antibodies raised against this antigen revealed by western blotting and
immunoprecipitation analyses showed the existence of another antigenic component
of 50-55 kDa in the UAg preparation. The antiserum was also used for screening of
a T. cruzi expression library. Sequencing of inserts from selected cDNA clones
showed high homology with the 3' end of the T.cruzi beta-tubulin gene sequence
encoding for the C-terminus of the protein. The presence of T. cruzi tubulin in
the UAg was confirmed by immunoprecipitation of a 50-55-kDa protein from 125I
labeled UAg with monoclonal antibodies (MAbs) to human alpha/beta-tubulin.
Interestingly, MAbs recognized radiolabeled T. cruzi tubulin eliminated in the
urine of infected mice 24 hr postinoculation of [35S]methionine-labeled viable
trypomastigotes. Tubulin found in the urine proved to be of T. cruzi origin
because this protein could not be identified in urinary specimens from uninfected
animals or mice acutely infected with Leishmania infantum or Toxoplasma gondii.
We conclude that tubulin is one of the parasite antigens eliminated in the urine
of T. cruzi-infected hosts. This finding may be used to develop a noninvasive
procedure for early diagnosis of Chagas' disease.
PMID- 9645866
TI - New data on the early development of Hysterothylacium aduncum (Nematoda,
Anisakidae).
AB - This note reports on incidental observations of the early development of the
third-stage larvae of Hysterothylacium aduncum from gadid fishes. Gravid H.
aduncum females were collected from Pollachius virens, Pollachius pollachius.
Gadus morhua, and Molva molva in Norwegian waters. The eggs were incubated at 20
per thousand salinity and 5 C. Spontaneous hatching of third-stage larvae was
observed 10-25 days after egg deposition. These larvae were long lived and could
infect Acartia tonsa copepods, the infections being maintained for up to 34 days.
The morphology of the third-stage larvae in the copepods and some traits of the
life cycle were similar to those reported in previous studies. However, our
results disagree with evidence suggesting that H. aduncum eggs rarely hatch, and
hatched larvae have lower survival and a poorer ability to infect the first
intermediate host than unhatched ones. It is difficult to account for these
discrepancies because information on the early development of Hysterothylacium
species is incomplete. However, we tentatively suggest that differences in the
early development of H. aduncum may indicate the existence of at least 2
different taxonomic entities in the North Atlantic, which is consistent with
previous evidence based on morphological traits.
PMID- 9645867
TI - Helminths of the Canadian toad, Bufo hemiophrys (Amphibia: Anura), from Alberta,
Canada.
AB - Forty adult Bufo hemiophrys from Alberta, Canada, were examined for helminths.
Four species were found: a trematode, Gorgoderina simplex, and 3 nematodes,
Cosmocercoides variabilis, Oswaldocruzia pipiens, and Rhabdias americanus.
Rhabdias americanus had the highest prevalence of helminths (73%); C. variabilis
had the highest mean intensity (26+/-33 SD). Bufo hemiophrys represents a new
host record for each species of helminth.
PMID- 9645868
TI - Adaptation of a strain of Plasmodium vivax from Mauritania to New World monkeys
and anopheline mosquitoes.
AB - A strain of Plasmodium vivax from Mauritania was adapted to develop in Aotus
lemurinus griseimembra, Aotus nancymai, Saimiri boliviensis, and hybrid Aotus
monkeys. Infections were induced via the inoculation of sporozoites dissected
from the salivary glands of Anopheles gambiae, Anopheles freeborni, and Anopheles
stephensi mosquitoes or the intravenous passage of infected erythrocytes.
Infections in 3 A. lemurinus griseimembra monkeys readily infected mosquitoes.
Four lines of the Mauritania parasites have been stored frozen for further
reference.
PMID- 9645869
TI - Serologic prevalence of Toxoplasma gondii in chickens in Madras, India.
AB - Serum samples from 185 chickens (Gallus gallus) collected from the various
slaughter markets in and around Madras City, India were examined for antibodies
to Toxoplasma gondii using the modified agglutination test incorporating
mercaptoethanol. Antibodies (> or = 1:25) to T. gondii were found in 39.5% of
sera. Antibody titers of individual sera (% in parentheses) were 1:25 (8.1%),
1:50 (10.8%), 1:100 (6.5%), 1:200(2.7%), 1:400 (4.3%), 1:800 (5.9%) 1:1,600
(0.5%), and 1:3,200 (0.5%).
PMID- 9645871
TI - Comparative observations on cercariae and metacercariae of Echinostoma trivolvis
and Echinoparyphium sp.
AB - Comparative observations were made on cercariae of Echinoparyphium sp. from Physa
gyrina in Charlie's pond, Stokes County, North Carolina and cercariae of
Echinostoma trivolvis from Helisoma trivolvis in Northampton County,
Pennsylvania. The cercaria of Echinoparyphium sp. has 43 collar spines, lacks
penetration and paraesophageal glands, and has a conical tail without fin folds.
The cercaria of E. trivolvis has 37 collar spines, penetration and paraesophageal
glands, a finger-like process at the tip of the tail and fin folds. The length of
the cercarial body and tail of E. trivolvis was significantly greater than that
of Echinoparyphium sp. Cercariae of both species encysted in Biomphalaria
glabrata snails in single and concurrent infections. In concurrent infections
with a single cercaria of each species, 2 encysted metacercariae were adjacent to
each other in the saccular kidney of the snail at 24 hr postinfection. The
diameter of encysted metacercariae of E. trivolvis was significantly greater than
that of Echinoparyphium sp. Echinoparyphium sp. metacercariae excysted at 39 C in
an alkaline trypsin-bile salts medium used previously to excyst E. trivolvis. The
length of excysted metacercariae of E. trivolvis was significantly greater than
that of Echinoparyphium sp.
PMID- 9645870
TI - Cryptosporidiosis in a bat (Eptesicus fuscus).
AB - Cryptosporidial infection was diagnosed histologically in the small intestine of
a big brown bat (Eptesicus fuscus) from Oregon. This is the first report of
cryptosporidiosis in a bat.
PMID- 9645872
TI - Intestinal parasite infections after extended use of chloroquine or primaquine
for malaria prevention.
AB - Comparative results of baseline and endpoint screening for intestinal parasites
are reported from Javanese men enrolled in a year-long, placebo-controlled
malaria prophylaxis trial in Irian Jaya. The objective was to detect nontarget
qualitative changes that may have resulted from prolonged chloroquine (300 mg
base weekly) or primaquine (0.5 mg base/kg daily) prophylaxis. Fresh fecal
specimens were examined (blinded trial) for parasites and ova using a modified
Kato-Katz thick smear method. More than 88% (94/106) of the baseline population
was infected by 1 or more parasite species of which hookworm and Blastocystis
hominis were dominant. Paired comparison between baseline and endpoint revealed
no significant changes within the primaquine or chloroquine groups with regard to
the variety of species found, the mean number of species or ova/subject, the
relative proportion of infections caused by these species, or the occurrence of
parasite-free, single, and multiple infections. Relative to placebo, there was a
significantly greater proportion of infections by Entamoeba histolytica/dispar
and a lower mean hookworm egg count in the chloroquine group. The endpoint
proportion of new or increased infections in the primaquine group was
significantly lower than that of the chloroquine group but comparable to that of
the placebo. Despite the dosage employed, the frequency and duration of use, and
excretion primarily through the bowels as the active parent compound, primaquine
appeared to have little or no significant effect against a variety of common
intestinal parasites. These largely negative results lend support for the safety
and acceptability of primaquine as a daily malaria prophylactic in a population
frequently at risk of intestinal helminth infections.
PMID- 9645873
TI - First records of Amblyomma americanum, Ixodes (Ixodes) dentatus, and Ixodes
(Ceratixodes) uriae (Acari: Ixodidae) from Maine.
AB - The first records of 3 ixodid tick species collected in the state of Maine are
reported. A total of 23 records of the lone star tick, Amblyomma americanum (L.,
1758), in 11 counties from hosts with no history of travel outside the state
demonstrates that this tick is now a resident of Maine. Ixodes dentatus Marx,
1899 is recorded from Waldo and Lincoln counties, and Ixodes uriae White, 1852 is
recorded from Matinicus Rock in Knox County. This is the first report of I. uriae
from the eastern United States. Disease agents such as those causing human
monocytic ehrlichiosis, Lyme disease, Rocky Mountain spotted fever, and several
arboviruses have been recorded from 1 or more of these tick species.
PMID- 9645874
TI - Effects of macrocyclic lactones on ingestion in susceptible and resistant
Haemonchus contortus larvae.
AB - The effects of ivermectin and ivermectin aglycone on pharyngeal uptake of a
carbohydrate substrate (3H-inulin) were measured in larvae of a macrocyclic
lactone (ML)-susceptible isolate and 2 ML-resistant isolates of Haemonchus
contortus. The resistant isolates showed a tolerance (in terms of the
concentration of compound required to reduce feeding to 50%) toward ivermectin of
approximately 4.5- and 9-fold and toward ivermectin aglycone of approximately 14
fold, compared to the susceptible isolate. This indicates that susceptible and
resistant isolates can be readily distinguished on the basis of the sensitivity
of pharyngeal uptake to MLs. The use of various metabolic inhibitors in this
assay system did not reveal the nature of the resistance mechanism. Pretreatment
of resistant larvae with inhibitors of multidrug resistance mechanisms (P
glycoprotein and multidrug resistance protein) and detoxification enzymes
(monooxygenases, esterases, and glutathione transferases) did not reduce their
level of tolerance to the ivermectin aglycone.
PMID- 9645875
TI - Complete development of the porcine coccidium Isospora suis Biester, 1934 in cell
cultures.
AB - Development from inoculated sporozoites to unsporulated oocysts of Isospora suis
Biester, 1934 is described in a swine testicular (ST) cell line. Sporozoites
penetrated ST cells within 1 hr postinoculation (PI). Development was initially
by endodyogeny to produce binucleate type I meronts and type I merozoites.
Division by endodyogeny continued during the 13-day observation period and type I
merozoites were the developmental stages most abundant at observation periods >3
days PI. Mutinucleate type II meronts and type II merozoites were first observed
7 days PI. Gamonts and oocysts were present 12 days PI. Oocysts did not sporulate
in vitro. The ultrastructural features of stages were similar to those that occur
in the pig host.
PMID- 9645876
TI - Axenic cultivation of Trichomonas vaginalis in a serum-free medium.
AB - Mammalian serum or bovine serum albumin are essential for Trichomonas vaginalis
cultivated under axenic conditions. Unfortunately, these components inhibit
several biological properties of these parasites. PACSR is a serum replacement,
free of bovine serum albumin. used for axenic cultivation of Entamoeba
histolytica. We show that PACSR is also useful for axenic cultivation of T.
vaginalis. Tubes containing 5.5 ml PEHP, or TYI basal media, plus 8% PACSR (v/v),
were inoculated with 10(3) trichomonads/ml from 3 strains (GT-3, GT-13, and GT
15) and incubated at 36.5 C for 72 hr. Depending on the strain, cultures grown in
PEHP plus PACSR reached densities of 50% (GT-13), 63% (GT-3), or 82% (GT-15) as
compared to controls grown in PEHPS. On the other hand, yields of GT-3, GT-13,
and GT-15 maintained in TYI plus PACSR were, respectively, 53%, 57%, and 67%
among those of cultures grown in TYI-S-33. In all experiments, PEHPS and TYI-S-33
contained 8% bovine serum. Yields reached in PEHPS were 2.07+/-0.275 to 4.83+/
4.41 x 10(6) trichomonads/ml, whereas in TYI-S-33, densities were 1.68+/-0.315 to
4.16+/-8.07 x 10(6) trichomonads/ml. In conclusion, PACSR added to PEHP or TYI
media is useful for axenic cultivation of T. vaginalis in the absence of serum or
bovine serum albumin. PACSR could be useful in performing analyses of biological
properties that are inhibited by serum or any of its components.
PMID- 9645877
TI - Genotypic analysis of Toxoplasma gondii isolates from pigs.
AB - To determine the prevalence of the 3 primary clonal lineages of Toxoplasma gondii
(strain types I, II, and III) in a potential food source of infection for humans,
we analyzed 43 isolates of T. gondii that had been collected from pigs at an
abattoir in Iowa. Parasites were harvested as in vitro-grown tachyzoites, and
their genotypes were determined at the SAG1 and SAG2 loci. On the basis of the
allele identified at the SAG2 locus, isolates were grouped into 1 of the 3
primary lineages. Type II strains were by far the most prevalent, accounting for
83.7% of the isolates. The type III genotype was identified in only 16.3% of the
isolates. These prevalences differ significantly from a previous sampling of
isolates from animals but are similar to the frequencies with which they occur in
human disease cases. Similar to the previously characterized strain P89, strains
P62 and P105 appeared to have recombinant genotypes. The type I genotype was not
identified in the isolates from pigs although these strains have previously been
shown to account for approximately 10-25% of toxoplasmosis cases in humans.
PMID- 9645878
TI - Analysis of anti-Trypanosoma cruzi antibody isotype specificities by western blot
in sera from patients with different forms of Chagas' disease.
AB - Infection of humans with Trypanosoma cruzi leads to either a lifelong
asymptomatic infection or to symptomatic presentations such as cardiomyopathy,
mega-syndromes, or both. The reasons for the different clinical manifestations
are not understood. We have previously studied a group of chronically infected
individuals with different clinical forms of Chagas' disease and found that the
levels of some anti-T. cruzi antibody isotypes, analyzed by enzyme-linked
immunosorbent assay, differed among patients with different clinical
presentations. We have expanded these studies to examine the antigen specificity
of these patients' IgG1, 2, 3, IgM, and IgA by western blot. We observed that
binding of particular antigens by some antibody isotypes were more prevalent in
some clinical groups as compared to others. For example, IgG3 from 13 of 19 (68%)
individuals with digestive manifestations bound a 68-kDa antigen, but only 3 of
31 (9%) individuals with cardiac involvement detected this same moiety. We also
found that, regardless of the clinical group, the profiles of antigens recognized
by each antibody isotype differs dramatically from the profiles recognized by
each other isotype. Together with our previous observations demonstrating that
the levels of anti-parasite antibody isotypes correlates with the clinical form,
these data suggest that overall anti-T. cruzi antibody reactivities may indeed be
skewed toward different antigens in individuals with different clinical
presentations.
PMID- 9645879
TI - Reduced expression of lipophosphoglycan (LPG) and kinetoplastid membrane protein
(KMP)-11 in Leishmania donovani promastigotes in axenic culture.
AB - The expression of surface lipophosphoglycan (LPG) and the lipophosphoglycan
associated kinetoplastid membrane protein (KMP)-11 was studied in the strain AG83
of Leishmania donovani in axenic culture. The expression of LPG and KMP-11
decreased along with parasite virulence as a function of the time of the
subculture.
PMID- 9645880
TI - Ancylostoma duodenale is responsible for hookworm infections among pregnant women
in the rural plains of Nepal.
AB - Fecal specimens from 292 pregnant women (ages 15-40 yr) and 129 infants (ages 10
20 wk) were examined for helminth eggs by the Kato-Katz method and cultured for
helminth larvae identification using a modified Harada Mori method. These
specimens were collected from June 1995 through July 1996 in Sarlahi District in
the southern rural plains of Nepal. Among pregnant women, the prevalence of
helminth infection by the Kato-Katz method was 78.8%, 56.2%, and 7.9% for
hookworm, Ascaris lumbricoides, and Trichuris trichiura, respectively. Using the
modified Harada-Mori method, 66.1% and 2.0% of women's fecal cultures were
positive for hookworm and Strongyloides stercoralis, respectively. All of the
cultured hookworm larvae were identified as Ancylostoma duodenale. Among infants,
1 specimen was positive for hookworm and 1 for A. lumbricoides using the Kato
Katz method. The modified Harada Mori method detected no larvae in specimens from
infants. There was 81.8% agreement between the 2 methods for the detection of
hookworm infection. Ancylostoma duodenale is endemic in this study population and
highly prevalent in pregnant women.
PMID- 9645881
TI - Antigenic similarity between Hammondia hammondi and Toxoplasma gondii
tachyzoites.
AB - Hammondia hammondi is an obligate heteroxenous intestinal coccidian of cats,
sharing many characteristics with Toxoplasma gondii. The tachyzoite stage
antigens of T. gondii and H. hammondi were studied by immunofluorescence assays
(IFA) and western blotting (WB) techniques to demonstrate antigenic similarities.
Five monoclonal antibodies (MAbs), anti-T. gondii antigens, P22, P23, P30, P35,
and P43, and mice polyclonal anti-H. hammondi serum were investigated. Antigens
of H. hammondi were recognized by anti-P30 MAb both in IFA and in WB and by anti
P22 and anti-P35 MAbs only in IFA. Polyclonal anti-H. hammondi serum revealed
many common antigens between the 2 parasites (30, 32, 35, 66, and 90 kDa). The
differences of host parasite relationship between these 2 coccidians lead us to
suggest that many of these antigens with similar molecular weights are not the
same, but homologous, molecules or that they are not the only factors involved in
these differences.
PMID- 9645882
TI - A chicken anti-conoid monoclonal antibody identifies a common epitope which is
present on motile stages of Eimeria, Neospora, and Toxoplasma.
AB - The chicken monoclonal antibody (mAb) 6D12-G10, raised against Eimeria acervulina
sporozoites, has previously been shown to recognize the conoid of E. acervulina
sporozoites and inhibit sporozoite invasion of lymphocytes in vitro. In indirect
immunofluorescent assay, the mAb 6D12-G10 also reacted with merozoites from E.
acervulina and identified a 21-kDa merozoite protein on western blots. By
confocal laser scanning microscopy, the conoid of sporozoites from 6 different
avian Eimeria species (E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox,
and E. tenella) were reactive with 6D12-G10 mAb. Furthermore, the 6D12-G10 mAb
also showed cross-reactivity with motile stages of 2 closely related
apicomplexans, Neospora, and Toxoplasma. These results indicate that the mAb 6D12
G10 identifies a conserved epitope on the conoid that is important in host cell
invasion by the apicomplexan parasites.
PMID- 9645883
TI - Efficacy of moxidectin 2% oral gel against second- and third-instar Gasterophilus
intestinalis De Geer.
AB - In a trial designed to evaluate the efficacy of the recommended dosage of
moxidectin 2% oral gel against the gastric stages of Gasterophilus spp., 14
ponies were selected from a herd on the basis of the inclusion criterion of the
presence of Gasterophilus spp. eggs attached to their hair coats. After random
allocation, the ponies were treated with 1 of 2 treatments, moxidectin 2% equine
gel in a single dose at the commercial dosage of 400 microg moxidectin/kg body
weight or placebo gel. The animals were necropsied 14 days posttreatment.
Efficacies against second- and third-instar Gasterophilus intestinalis De Geer
were 100% and 99.5%, respectively.
PMID- 9645884
TI - Experimental transmission of the nematode Echinomermella matsi to the sea urchin
Strongylocentrotus droebachiensis in the laboratory.
AB - Three experiments were conducted to investigate the possibility of maintaining
the Echinomermella matsi-Strongylocentrotus droebachiensis system in the
laboratory. The experiments were performed by injecting E. matsi larvae taken
directly from gravid female nematodes into the mouths of sea urchins. In all
experiments, this treatment resulted in a higher infection in treated animals
than in unmanipulated controls. The successful establishment of larvae indicates
that E. matsi has a monoxenous life cycle. The growth of larvae in experimentally
infected hosts was slow, indicating that the generation time of the parasite is
of the same magnitude as the life expectancy of the host, 1-2 yr. This slow
growth rate suggests that considerable resources will be needed to maintain the
system in the laboratory.
PMID- 9645885
TI - Sarcocystis-associated encephalitis and myocarditis in a wild turkey (Meleagris
gallopavo).
AB - A Sarcocystis-like organism was associated with encephalitis and myocarditis in
an ataxic, emaciated adult male turkey (Meleagris gallopavo) from Gilmer County,
West Virginia. Protozoal schizonts and merozoites were associated with areas of
inflammation and occasionally necrosis in both the heart and the brain. The
organisms divided by endopolygeny and stained positively with anti-Sarcocystis
cruzi serum in an immunohistochemical test.
PMID- 9645886
TI - Twenty-two-year follow-up in the VA Cooperative Study of Coronary Artery Bypass
Surgery for Stable Angina.
AB - We evaluated the 22-year results of initial coronary artery bypass surgery with
saphenous vein grafts compared with initial medical therapy on survival,
incidence of myocardial infarction, reoperation, and symptomatic status in 686
patients (average age 51) with stable angina in the Veterans Affairs Cooperative
Study of Coronary Artery Bypass Surgery. Between 1972 and 1974, 354 patients were
assigned to medical treatment and 332 to surgical revascularization. In the
surgical cohort, 312 patients underwent operation (operative mortality 5.8%) and
25% subsequently underwent repeat operation (operative mortality 10.3%). In the
medical cohort, 160 patients crossed over to surgery (operative mortality 4.4%)
and 21% of these patients had reoperation (operative mortality 9.1%). Neither
crossover nor reoperation was predictable by angiographic or clinical risk
factors measured at baseline. The overall 22-year cumulative survival rates were
25% and 20% in the medical and surgical cohorts (p = 0.24). Corresponding rates
in low-risk patients who had 1 or 2 vessels diseased, or 3 vessels diseased with
normal left ventricular function were 31% and 24% (p = 0.024). Although
significant at 10 years, there was also no long-term survival benefit for high
risk patients assigned to bypass surgery. The probabilities of remaining free of
myocardial infarction and of being alive without infarction were significantly
higher with initial medical therapy, 57% versus 41% (p = 0.02) and 18% versus 11%
(p = 0.0031), respectively. This trial provides strong evidence that initial
bypass surgery did not improve survival for low-risk patients, and that it did
not reduce the overall risk of myocardial infarction. Although there was an early
survival benefit with surgery in high-risk patients (up to a decade), long-term
survival rates became comparable in both treatment groups. In total, there were
twice as many bypass procedures performed in the group assigned to surgery
without any long-term survival or symptomatic benefit.
PMID- 9645887
TI - Comparison of results and risk factors of cardiac surgery in two 3-year time
periods in the 1990s.
AB - With the increasing number of treatment options for heart disease, decision
making requires profiles of risk for conventional cardiac surgery. Refinements in
techniques and clinical practices seem to have reduced surgical risk. This study
was performed to determine current risk factors. From July 1, 1990, to June 30,
1996, 1,036 consecutive patients underwent 1,042 heart operations using standard
incisions and cardiopulmonary bypass with cardioplegia. Univariate and
multivariate analyses using a logistic regression model were performed to
determine factors significant for combined 30-day and hospital mortality. To
determine if there were trends in the results and the risk factors, the last 500
consecutive cases in the series were analyzed separately. Overall, 30-day
mortality was 17 of 1,042 (1.6%) and combined 30-day and hospital mortality was
27 of 1,042 (2.6%). Significant risk factors for combined 30-day and hospital
mortality by multivariate analyses were: emergent/resuscitative status,
preoperative dialysis, left ventricular ejection fraction < or = 30%, valve
operation, and creatinine > or = 1.5 mg/dl. Comparison with baseline
characteristics of the patients undergoing the last 500 consecutive operations to
the earlier 542 operations in the study group showed that risk factors had a very
similar profile for the 2 groups. The overall 30-day mortality for the last 500
consecutive operations was 5 of 500 (1.0%) and combined 30-day and hospital
mortality was 8 of 500 (1.6%). The significant risk factors by multivariate
analyses were reduced to left ventricular ejection fraction < or = 30% and
creatinine > or = 1.5 mg/dl. These results indicate that modern techniques and
clinical practices have mitigated well-recognized risk factors in conventional
cardiac surgery and this trend is ongoing.
PMID- 9645888
TI - Prognostic role of troponin T versus troponin I in unstable angina pectoris for
cardiac events with meta-analysis comparing published studies.
AB - Controversy exists as to the clinical roles and relative specificities of cardiac
troponin T or I in patients with unstable angina pectoris (UAP). We measured
troponin T and I levels on admission in 123 patients with UAP. Of the 107
patients with normal creatine kinase during the first 24 hours, troponin T and I
were elevated in 14 and 13 patients, respectively. At 30 days, 5 of 14 patients
(36%) with elevated troponin T and 3 of 93 patients (3.2%) with normal troponin T
had acute myocardial infarction (odds ratio [OR], 16.7; 95% confidence interval
[CI] 3.4 to 81.5; p <0.001). Of 13 patients with elevated troponin I, 5 patients
(39%) and 3 of 94 patients (3.2%) with normal troponin I had acute myocardial
infarction (odds ratio, 21.7; 95% CI 4.3 to 110; p <0.001). No deaths occurred
within 30 days. Both markers demonstrated equivalent sensitivity (63%) and
specificities (troponin T: 91%; troponin I: 92%) for myocardial infarction. Meta
analysis of 12 published troponin T and 9 troponin I studies in patients with UAP
produced risk ratios of 4.2 (95% CI 2.7 to 6.4, p <0.001) for troponin I compared
with 2.7 (95% CI 2.1 to 3.4, p <0.001) for troponin T. Comparison of the
sensitivities and specificities of both markers using summary receiver operating
characteristic curves showed no significant difference in their abilities to
predict acute myocardial infarction and cardiac death. Troponin T and I show
similar prognostic significance for acute myocardial infarction or death in the
same patients with UAP. The 2 markers are equally sensitive and specific, as
confirmed by meta-analysis, and this supports a role in risk stratification.
PMID- 9645889
TI - Usefulness of pulse-wave Doppler tissue sampling and dobutamine stress
echocardiography for the diagnosis of right coronary artery narrowing.
AB - To study the feasibility and diagnostic accuracy of right coronary artery (RCA)
narrowing by right ventricular (RV) pulse-wave Doppler tissue sampling during
dobutamine stress echocardiography (DSE), 30 patients (mean age 55 +/- 9.5 years,
26 men) with suspected coronary artery disease underwent DSE (up to 40
microg/kg/min with additional atropine during submaximum heart rate responses).
Pulse-wave Doppler tissue sampling of RV free walls close to the tricuspid
annulus was performed in the apical 4-chamber view. The maximum velocity during
the ejection phase, early, and late diastole was measured. Data from 5
consecutive beats were averaged. The measurements were repeated at rest, at low
dose (10 microg/kg/min), and at peak dobutamine stress. The results were
evaluated for the prediction of significant proximal or medium RCA narrowing (>
or = 50% diameter stenosis, assessed by quantitative coronary angiography within
the previous 3 months). A progressive increase of the ejection phase velocity (>
25% between 10 microg/kg/min and peak stress) was predictive of a normal RCA,
whereas a blunted increase and/or decrease (< 25% of increase) was predictive of
significant RCA narrowing: sensitivity (95% confidence intervals): 82% (68 to
96), specificity: 78% (67 to 93), positive predictive value: 69% (52 to 86),
negative predictive value: 88% (75 to 100), accuracy: 79% (65 to 94). Pulse-wave
Doppler tissue sampling provided analyzable data in 100%, whereas the visual
assessment of gray-scale images was possible only in 90%. Thus, in patients with
suspected RCA narrowing, pulse-wave Doppler tissue sampling during DSE was able
to diagnose significant RCA narrowing.
PMID- 9645890
TI - Effects of practice setting on quality of lipid-lowering management in patients
with coronary artery disease.
AB - We undertook a study to determine whether there were differences in the quality
of lipid management in patients with coronary artery disease (CAD) in 2 different
practice settings (which represent different socioeconomic classes), and to
determine the level of compliance with the National Cholesterol Education Program
guidelines by academic physicians in managing patients with CAD. A retrospective
cross-sectional study was performed using a systematic chart review of 270
medical records (131 from the cardiology clinic, 139 from the cardiology private
practice) of patients with known CAD at an academic tertiary care center in New
York City. The total proportion of patients with CAD having a lipid profile
ordered in the clinic and private suite was 43%. Of these people, 22% had a low
density lipoprotein cholesterol (LDL) < or = 100 mg/dl and 54% had an LDL < or =
130 mg/dl (10% and 23% of the total population, respectively). The total
proportion of patients taking lipid-lowering medications was 29%. When comparing
the quality of treatment between the 2 settings, there were no statistically
significant differences in the percentages of patients who had lipid profiles
measured (40% clinic vs 47% private suite, p >0.10), in the percentage of
patients with LDL < or = 130 mg/dl (50% clinic vs 57% private suite, p >0.10) or
in the weighted percentage of patients taking lipid-lowering medications (29%
clinic vs 48% private suite, p = 0.099). The performances of individual
physicians, however, varied widely. The percentages of patients with lipid
profiles measured by individual physicians ranged from 0% to 83%, while the
percentages of patients on drug treatment by a physician ranged between 10% and
88%. These findings indicate that socioeconomic differences, represented by
different practice settings, do not account for differences in the screening for,
control of, or use of medications in managing hyperlipidemia. Rather, individual
physicians are accountable for differences in lipid management.
PMID- 9645891
TI - Cardiac release and kinetics of endothelin after uncomplicated percutaneous
transluminal coronary angioplasty.
AB - This study was designed to assess the release kinetics of endothelin after
percutaneous transluminal coronary angioplasty (PTCA) and to prove the coronary
endothelium as the source of the endothelin release. Twenty-seven patients with
single-vessel coronary artery disease underwent PTCA. Endothelin, troponin T,
myoglobin, and creatine phosphokinase paired blood samples were withdrawn from
the coronary sinus and a peripheral vein before the balloon maneuver and at 1, 5,
10, 30, 45 minute(s), and at 1, 2, 3, 6, 12, and 24 hour(s) after the last
balloon maneuver. Myocardial ischemia was monitored by means of cardiac lactate
metabolism and 12-lead electrocardiogram. Thirteen patients who underwent a
diagnostic cardiac catheterization served as a control group. In the left
coronary artery, PTCA (n = 19) endothelin concentrations increased from 4.1 pg/ml
as a common mean baseline level before intervention to 13.9 +/- 2.6 pg/ml (mean
+/- SD) in the coronary sinus and 7.9 +/- 2.2 pg/ml (mean +/- SD) in the
peripheral vein at 1 minute after the intervention (p <0.001). The levels
remained elevated for 3 hours with higher coronary sinus than peripheral venous
concentrations due to persistent cardiac endothelin release. PTCA of the right
coronary artery (n = 8) also led to an instantaneous endothelin increase from a
mean concentration of 4.4 before intervention to 8.3 pg/ml after intervention
with identical coronary sinus and peripheral venous levels (p <0.001). Endothelin
levels gradually decreased to normal within 6 hours. No patient developed a
measurable myocardial ischemia or a myocardial infarction. In the control group
all parameters remained unchanged. Uncomplicated PTCA was followed by a
significant cardiac endothelin release that seems to indicate endothelial injury
and not myocardial ischemia.
PMID- 9645892
TI - Quantitative angiography of coronary artery dimensions 24 hours after rotational
atherectomy.
AB - Rotational atherectomy results in platelet activation and heat generation, which
may impact artery size immediately after treatment. In addition, arteries treated
with balloon angioplasty may exhibit recoil within 24 hours. In this study,
arteries treated with rotational atherectomy, with and without adjunctive balloon
angioplasty, were analyzed by quantitative coronary angiography to determine the
effect of rotational atherectomy on the dynamic behavior of the arterial wall
within 24 hours after the procedure. Quantitative coronary angiography was
performed at a core laboratory. Coronary angiogram acquisitions were preceded by
intracoronary nitroglycerin injections and were repeated using identical angles
of projection. Proximal and distal reference vessel diameters were 2.55 +/- 0.60
and 2.28 +/- 0.51 mm, respectively, and did not change from pre- to
postprocedure. Both were larger the following day increasing to 2.72 +/- 0.65 and
2.52 +/- 0.52 mm, respectively, (p <0.001). Minimum luminal diameter (MLD)
increased from 0.70 +/- 0.28 mm before to 1.49 +/- 0.34 mm after the procedure
and to 1.72 +/- 0.37 mm at 24-hour follow-up (p <0.001). Subset analysis of
patients treated with rotational atherectomy alone or rotational atherectomy with
adjunctive balloon angioplasty revealed that the increase in luminal diameters
occurred in both subsets. Patients treated with adjunctive angioplasty had a
smaller initial MLD, a larger postprocedure MLD, and no difference in MLD at 24
hour follow-up compared with stand-alone rotational atherectomy. Subset analysis
of 100 patients who had 6-month follow-up angiography revealed that both a
calculated acute gain and chronic late loss, based on a 24-hour film, differed
significantly from values using a film acquired immediately after the procedure.
However, the slope of the linear regression between acute gain and chronic late
loss did not differ. Coronary arteries treated with rotational atherectomy with
or without adjunctive balloon angioplasty increase significantly in size during
the first 24 hours after the procedure. This phenomenon has implications for the
calculation of absolute gain and chronic late loss, but not for the linear
relation between the 2 quantitative outcomes.
PMID- 9645893
TI - Do physicians modify their prehospital management of patients in response to a
public campaign on chest pain?
AB - The goals of this study were to analyze the impact of a public campaign on chest
pain on physicians involved in the prehospital care of patients with this
symptom, in terms of physician delay, rates of immediate hospitalization, and of
transportation by ambulance. Prehospital delays and decisions for all 866
patients with chest pain managed by the community and generalist physicians or by
emergency physicians, who presented to the emergency department of a teaching
hospital during the 12 months of the campaign, were compared with those of all
749 patients with similar presentations during the 12 months before it. When
community and generalist physicians were involved, median (110 minutes) physician
delay did not decrease during the campaign, whereas it decreased from 65 to 56
minutes (p <0.003) when emergency physicians were involved. Rates of immediate
hospitalization (73%) and of transportation by ambulance (47%) of patients
managed by community and generalist physicians were unaffected by the campaign,
whereas they increased from 96% and 89%, respectively, to 98% (p = 0.09) and 94%
(p <0.02) when emergency physicians were involved. Similar observations were made
in patients with confirmed acute myocardial infarction and unstable angina and
remained highly significant after adjustment for differences in clinical
characteristics. Thus, community and generalist physicians did not significantly
modify their prehospital management of patients with chest pain despite a public
campaign. To be successful, guidelines on the matter have to be developed with
the active participation of these physicians.
PMID- 9645894
TI - Frequency analysis of human atrial fibrillation using the surface
electrocardiogram and its response to ibutilide.
AB - This study assesses a technique for quantifying the frequency spectrum of atrial
fibrillation (AF) using the surface electrocardiogram. Electrocardiograhic
recordings were obtained in 61 patients during AF. After bandpass filtering, the
QRST complexes were subtracted using a template-matching algorithm. The resulting
fibrillatory baseline signal was subjected to Fourier transformation and
displayed as a frequency power spectrum. These frequency spectra were compared to
direct measurements from the right atrium and coronary sinus in 35 patients
undergoing electrophysiologic study. The clinical use of this technique was
explored by correlating fibrillatory frequency with the behavior of the
arrhythmia in 26 patients referred for cardioversion. The electrocardiographic
frequency spectrum during AF was characterized by a single peak that varied
widely between patients (range 228 to 480 beats/min). There was a strong
correlation between electrocardiographic peak frequency and that measured in the
right atrium and coronary sinus (r = 0.79 to 0.98, p <0.0001). Episodes of AF
that terminated in < 5 minutes had a lower frequency than those that persisted >
5 minutes (324 +/- 36 vs 402 +/- 78 beats/min, p = 0.001). Chronic AF (< 3 months
in duration) had a lower frequency than chronic AF (present > 3 months) (336 +/-
48 vs 408 +/- 60 beats/ min, p = 0.012). Fibrillation frequency was an accurate
predictor of conversion with ibutilide. Success rate was 100% in patients with
peak frequency < 360 beats/min versus 29% in patients with frequencies > or = 360
beats/min (p = 0.003). Automatic analysis of the frequency content of the
fibrillatory baseline on the surface electrocardiogram accurately reflects the
average rate of AF. This measurement correlates with the clinical pattern of the
arrhythmia and predicts the response to administration of ibutilide.
PMID- 9645895
TI - Echocardiographic parameters for predicting maintenance of sinus rhythm after
internal atrial defibrillation.
AB - Chronic atrial fibrillation (AF), which is refractory to external electrical
direct current shock and/or pharmacologic cardioversion, may be successfully
cardioverted using internal atrial defibrillation. To avoid unnecessary
procedures, it is important to be able to predict which patients will revert to
AF. Thirty-eight patients with chronic AF underwent successful internal atrial
defibrillation and were followed for 6 months after restoration of sinus rhythm.
Left atrial (LA) diameter, left ventricular ejection fraction, maximum LA
appendage area, and peak emptying velocities of the LA appendage were analyzed to
determine which of these factors were associated with recurrence of AF. Forty
nine percent of patients had a recurrence of AF within 6 months following
internal atrial defibrillation. The preprocedural ejection fraction (mean +/- SD
59 + 14% vs 57 + 13%, p = 0.63), LA diameter (4.2 +/- 0.6 cm vs 4.5 +/- 0.6 cm, p
= 0.16), and LA appendage area (5.0 +/- 1.5 cm2 vs 5.8 +/- 1.5 cm2, p = 0.13) did
not differ significantly between patients who maintained sinus rhythm and those
who had recurrence of AF. Peak emptying velocities of the LA appendage before
cardioversion were significantly lower in patients with recurrence of AF compared
with patients who maintained sinus rhythm (0.26 +/- 0.1 m/s vs 0.49 +/- 0.17 m/s,
p = 0.001). A peak emptying velocity <0.36 had a sensitivity of 82% and a
specificity of 83% for predicting recurrence of AF.
PMID- 9645896
TI - Prospective comparison of flecainide versus sotalol for immediate cardioversion
of atrial fibrillation.
AB - This study sought to compare the efficacy and safety of intravenous flecainide
and sotalol for immediate cardioversion of atrial fibrillation. We performed a
prospective, randomized, single-blind, multicenter trial, including 106
hemodynamically stable patients with atrial fibrillation, stratified according to
duration of the arrhythmia. Exclusion criteria included severely reduced left
ventricular systolic function, recent antiarrhythmic therapy, and hypokalemia.
Patients were randomly assigned to receive either intravenous flecainide or
intravenous sotalol. Trial medication was given at a dose of 1.5 mg/kg body
weight (maximum 150 mg). Overall, 28 of 54 patients (52%) given flecainide and 12
of 52 patients (23%) given sotalol converted to sinus rhythm during the first 2
hours after start of the infusion (p = 0.003). Multivariate analysis confirmed
that treatment allocation to flecainide, an arrhythmia duration of < or = 24
hours, higher plasma magnesium level at baseline, higher age for men, and lower
age for women independently increases the probability of conversion. The
frequency of adverse effects was not significantly different in the 2 treatment
groups.
PMID- 9645897
TI - Effect of beta-blocker therapy in patients with coronary artery disease in New
York Heart Association classes II and III. The Bezafibrate Infarction Prevention
(BIP) Study Group.
AB - The aim of the study was to investigate the effect of beta-blocker treatment on a
large cohort of patients with coronary artery disease in functional classes II
and III according to the New York Heart Association (NYHA) classification. Among
11,575 patients with coronary artery disease screened for participation, but not
included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were
in NYHA classes II and III. In the latter group of patients we compared the
prognosis of 1,109 (34%) treated with beta blockers with 2,116 counterparts not
receiving beta-blocker therapy. After a mean follow-up of 4 years, all-cause and
cardiac mortality rates were significantly lower among beta-blocker users, 9% and
5%, respectively, than among beta-blocker nonusers, 17% and 11%, respectively (p
<0.01 for both). After multivariate adjustment, treatment with beta blockers was
associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95%
confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR =
0.61, 95% CI 0.45 to 0.83) than was no treatment with a beta blocker. Lower total
mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to
0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients
with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a
previous myocardial infarction. We conclude that beta-blocker therapy in coronary
patients in NYHA classes II or III is safe and associated with a lower risk for
all-cause and cardiac mortality.
PMID- 9645898
TI - Osteitis deformans (Paget's disease) and calcific disease of the heart valves.
AB - The prevalence of calcific aortic valve stenosis in Paget's disease (osteitis
deformans) was investigated by reviewing autopsy data of severe cases (> or = 75%
involvement of > or = 3 major bones, the femur, tibia, skull, and pelvis) and
moderate cases (> or = 75% involvement of only 1 or 2 major bones) of Paget's
disease. Comparisons were made with normal age-matched controls. Aortic stenosis
(AS) was present in 24% of 27 autopsies of severe Paget's disease compared with
3.5% in 201 controls (p <0.01). Clinical signs of AS were present in 39% of 102
patients with severe Paget's disease compared with 4% in 417 controls (p <0.101).
The prevalence of AS in 18 cases of moderate Paget's disease was similar to that
of controls. Electrocardiograms were reviewed in 45 cases of Paget's disease and
compared with 80 controls of similar age. Complete atrioventricular (AV) block,
incomplete AV block, bundle branch block, and left ventricular hypertrophy were
present in 11%, 11%, 20%, and 13% of the Paget's cases and in only 2.5%, 1.3%,
2.5%, and 3.8% in the control cases (p <0.05, <0.05, <0.01, and <0.05,
respectively). It is concluded that in severe Paget's disease there is a high
prevalence of AS, heart block, and bundle branch block, but these are not present
in moderate degrees of bone involvement.
PMID- 9645899
TI - Left ventricular systolic torsion and early diastolic filling by echocardiography
in normal humans.
AB - This study describes a novel 2-dimensional echocardiographic technique to measure
left ventricular (LV) systolic twist in humans and relates this measure to early
ventricular filling. LV twist is the counterclockwise rotation of the left
ventricle during systole when viewed from the apex. The effect of ventricular
twist has been postulated to store potential energy, which ultimately aids in
diastolic recoil, leading to ventricular suction. The generated negative early
diastolic pressures may augment early ventricular filling. We measured
ventricular twist in 40 patients with normal transthoracic echocardiograms. End
systolic twist was determined by measuring rotation of the anterolateral
papillary muscle about the center of the ventricle. LV filling was assessed by
analysis of transmitral Doppler flow velocities. The mean value obtained was 9 +/
7 degrees of rotation. Twist measurements were highly reproducible with an
intraobserver correlation coefficient of r = 0.881, p <0.001. The magnitude of
ventricular twist was strongly correlated positively with acceleration of the
mitral E-wave (r = 0.75; p <0.0001) and negatively with the mitral E-wave
acceleration time (r = -0.83; p <0.0001).
PMID- 9645900
TI - Colles-Stokes contributions to the concept of heart failure.
AB - "Colles fracture," "Colles law," "Stokes-Adams syndrome," "Cheyne-Stokes
respiration," and "Corrigan pulse" are some of the contributions of the Irish
school that are utilized for teaching purposes in medical schools and training
programs, as well as in daily practice of medicine. We wish to add an important
description by Drs. Colles and Stokes that personifies the considerable personal
contributions of these 2 physicians in our understanding of the pathophysiologic
expression of the syndrome of heart failure. The clinical-pathologic correlation
of the disease that affected Dr. Colles is well described by Dr. Stokes in his
treatise Diseases of the Heart and the Aorta. He recognized the cyclical nature
of frequent decompensations in heart failure, the relation of clinical worsening
in conjunction with reduced urine output, as well as the importance of
reestablishing urinary flow to achieve a decrease in dyspnea. Dr. Colles also
demonstrated a profound clinical insight when he noticed, first, that his
affliction was "eventually a fatal disease and that remedies that work may lose
effect over time," illustrating an observation that has stood the test of time
and, secondly, when he told Dr. Smith "... I would direct particular attention to
the heart and the lungs ... and the swelling in the right hypochondrium ... I
suspect that there is some connexion between this swelling of the hypochondrium
and the diseased state of the heart." We believe that the Colles-Stokes
contributions, both in the clinical as well as the clinical-pathologic arenas,
are one of the landmark descriptions that helped to evolve the concept of the
syndrome of heart failure.
PMID- 9645901
TI - Robert Ogden Bonow, MD: a conversation with the editor. Interview by William
Clifford Roberts..
PMID- 9645902
TI - Impact of exercise single-photon emission computed tomographic imaging on
appropriateness of coronary revascularization.
AB - This study examined the predictors of early coronary revascularization in 816
patients with chest pain syndromes who had coronary artery disease by angiography
and exercise single-photon emission computed tomography (SPECT) thallium imaging.
Multivariate analysis of clinical, stress, nuclear, and catheterization variables
revealed the presence of SPECT reversibility as the most powerful predictor (chi
square = 43) of early revascularization.
PMID- 9645903
TI - Usefulness of technetium-99m sestamibi infarct size in predicting posthospital
mortality following acute myocardial infarction.
AB - In this multicenter study, 249 patients who underwent tomographic technetium-99m
sestamibi infarct size measurement at hospital discharge were followed up for a
median duration of 7 months. Infarct size was significantly associated with
mortality (chi-square = 5.8, p = 0.02) and could stratify patients into lower and
higher risk subsets: 1-year mortality 2% for infarct size < 14% versus 8% for
infarct size > or = 14% of the left ventricle.
PMID- 9645904
TI - Inhaled nitric oxide improves exercise capacity in patients with severe heart
failure and right ventricular dysfunction.
AB - Fourteen cardiac transplant candidates were studied with cardiopulmonary exercise
testing at baseline and while breathing nitric oxide (40 ppm). Oxygen consumption
at the anaerobic threshold was improved by breathing nitric oxide in patients
with pulmonary hypertension and in patients with an elevated left ventricular end
diastolic volume index.
PMID- 9645905
TI - Reproducibility of the six-minute walking test in patients with chronic
congestive heart failure: practical implications.
AB - This study assesses the reproducibility of the 6-minute walking test in patients
with chronic heart failure using 2 different measurement protocols. Practical
suggestions for the clinical setting are given.
PMID- 9645906
TI - Practices and attitudes concerning oral health in pediatric cardiology clinics to
prevent infective endocarditis.
AB - A survey of 121 pediatric cardiology clinics investigated the current practices
and attitudes toward oral health education and oral screenings in pediatric
cardiology clinics for patients susceptible to infective endocarditis. Most
pediatric cardiology clinics do not provide oral health education and oral
screenings, but believe it would be beneficial.
PMID- 9645907
TI - Improved clinical effectiveness with a collagen vascular hemostasis device for
shortened immobilization time following diagnostic angiography and percutaneous
transluminal coronary angioplasty.
AB - This study prospectively compared immobilization time followed by use of a
vascular hemostasis device (VasoSeal) versus manual compression to achieve
hemostasis at the arterial puncture after angiography and percutaneous
transluminal coronary angioplasty (PTCA). The trial shows that use of a vascular
hemostasis device results in earlier mobilization, even in highly anticoagulated
PTCA patients compared with manual compression, with no statistically significant
complications.
PMID- 9645908
TI - PR-segment deviation as the initial electrocardiographic response in acute
pericarditis.
AB - PR-segment deviations precede classic ST(J) deviations in acute pericarditis
because the superficial myocarditis producing electrocardiographic changes is
more encompassing in the thin atrial muscle. In patients with appropriate
syndromes, PR-segment deviations should be recognized early after onset, as ST
changes may be absent.
PMID- 9645909
TI - Determination of pretest probability for detection of a cardiovascular source of
emboli by transesophageal echocardiography using clinical and transthoracic
echocardiographic data.
AB - Transesophageal echocardiographic findings and their effect on disease management
were evaluated in 216 patients with suspected cardiovascular source of emboli.
Clinical and transesophageal echocardiographic findings were useful in defining
pretest probability for finding a probable cardiovascular source of emboli on
transesophageal echocardiography.
PMID- 9645910
TI - A World Wide Web site for low-density lipoprotein receptor gene mutations in
familial hypercholesterolemia: sequence-based, tabular, and direct submission
data handling.
AB - Familial hypercholesterolemia is an autosomal dominant inherited condition
characterized by a mutation in the low-density lipoprotein receptor (LDLR) gene.
A database has been set up on the World Wide Web for mutations in the LDLR gene.
PMID- 9645911
TI - Effect of mitral regurgitation on thromboembolic risk in patients with rheumatic
mitral valve disease.
PMID- 9645912
TI - Interrupted inferior vena cava in asplenia syndrome.
PMID- 9645913
TI - Evaluation of a modified APTT-based method for determination of APC resistance in
plasma from patients on heparin or oral anticoagulant therapy.
AB - An APTT-based kit method (Coatest APC Resistance), modified by predilution 1+4 of
sample plasma in a plasma diluent containing a heparin antagonist (V-DEF plasma),
has been evaluated on plasmas from patients treated with unfractionated (n = 110)
or either of three different low molecular heparins (n=44), or with oral
anticoagulants (n=147). Irrespective of treatment, no difference was observed in
the APC response as compared to untreated individuals (n=62), and a complete
discrimination was obtained between individuals with a normal factor V genotype
and those carrying the FV:Q506 mutation. Furthermore, in contrast to the
original, APTT-based kit method, where anticoagulant therapy results in a
prolongation of the APTT, the modified kit provided APTT values within the normal
range for orally anticoagulated (INR< or =6) and for all heparin treated (< or =1
IU/mL) patients except for one with a suspected presence of phospholipid
antibodies. Due to the predilution in V-DEF plasma, contamination with platelets
up to 1.5 x 10(4)/microL had a negligible effect on analysis of frozen plasmas
regarding their classification as normal or abnormal. Analyses of fresh plasmas
show no influence at platelet counts up to 6x10(4)/microL. Consequently,
negligible differences in APC ratios were obtained between fresh and frozen
plasmas. In conclusion, the modified kit method is applicable to plasmas from
anticoagulated patients as well as from untreated individuals, allowing a safe
assignment regarding the presence or absence of the FV:Q506 genotype.
PMID- 9645914
TI - The Arg506Gln mutation (FV Leiden) among a cohort of 4188 unselected Danish
newborns.
AB - Resistance to activated protein C (APC) is the most prevalent single phenomenon
associated with thromboembolic disease. It is caused by a single point mutation
in the factor V gene (Arg506Gln or FV Leiden), replacing an Arg506 with a Gln at
the APC-cleavage site in factor V. In this study we present a prevalence study of
the Arg506Gln mutation in a large Danish cohort. By screening 4188 newborns (8376
alleles) we identified 3.4% alleles (95% CI: 3.0-3.8) of the Arg506Gln mutation,
corresponding to a heterozygous prevalence of 6.6% (95% CI: 5.9-7.4) in Denmark.
This is significantly lower than what has been reported from southern Sweden. The
birth cohort has been selected from the entire country, providing representative
and accurate estimates of the gene frequencies. Equal gender distribution was
found, and the Arg506Gln mutation is probably not a considerable risk factor in
fetal life in the general population.
PMID- 9645916
TI - Mathematical model for the blood coagulation prothrombin time test.
AB - A mathematical model for the prothrombin time test is proposed. The time course
of clotting factor activation during coagulation was calculated, and the
sensitivity of the test to a decrease in the concentrations of coagulation
proteins or their activities was studied. The model predicts that only severe
coagulation disorders connected with a more than five-fold decrease in the
concentrations or activities of the blood coagulation factors can be revealed by
the test.
PMID- 9645915
TI - Oral antiplatelet efficacy of the platelet GPIIb/IIIa antagonist, DMP754 in non
human primates.
AB - Binding kinetic studies with XV459, the active form of DMP754, demonstrated
comparable binding kinetics (Kd and Koff) with platelets obtained from either
human or baboons which were different from that with platelets obtained from
dogs. Therefore, the present study was undertaken to evaluate the antiplatelet
efficacy of DMP754 following oral administration in baboons. The dose levels
evaluated were 0.1 and 1.0 mg/kg, IV and 0.1, 0.3, 1.0, and 3.0 mg/kg, oral of
DMP754. Oral doses of DMP754 resulted in dose- and time-related inhibition of
platelet aggregation along with a modest effect on bleeding time prolongation.
DMP754 at similar oral doses had 24 hours of antiplatelet effects in baboon as
compared to 8-12 hours duration of antiplatelet efficacy in dogs. At maximal
antiplatelet doses DMP754 demonstrated no significant effects on platelet count,
clinical chemistry or hemodynamic profiles in baboons. These data suggest that
DMP754 is a potent orally active antiplatelet agent with extended duration after
once a day oral administration in non-human primate.
PMID- 9645917
TI - Effects of various doses of antithrombin III on endotoxin-induced endothelial
cell injury and coagulation abnormalities in rats.
AB - We previously demonstrated that antithrombin III reduced the injury to
endothelial cells caused by activated leukocytes in rats administered endotoxin.
This occurred via the increase of the endothelial release of prostaglandin I2,
which is a potent inhibitor of leukocyte activation. We evaluated the dose of
antithrombin III required to prevent such endothelial cell injury in rats
administered endotoxin, by comparing the effects of various antithrombin II doses
on the pulmonary vascular injury. The intravenous administration of endotoxin, 5
mg/kg, produced a transient accumulation of leukocytes in the lung, followed by
pulmonary vascular injury, as indicated by an increase in the pulmonary vascular
permeability, and coagulation abnormalities. The dose of 250 U/kg significantly
inhibited all such effects of endotoxin. While lower doses of antithrombin III
(50 and 100 U/kg) significantly inhibited such coagulation abnormalities, they
failed to prevent either the pulmonary accumulation of leukocytes or the
subsequent pulmonary vascular injury. Rats administered endotoxin exhibited an
accumulation of neutrophils and edematous changes in the pulmonary interstitial
space. Although such changes were reduced after 250 U/kg of antithrombin III,
they were unaffected by lower doses of 50 and 100 U/kg. Plasma levels of 6-keto
PGF1alpha were markedly increased in rats 90 min after the administration of
endotoxin, and were significantly decreased in the endotoxin-treated rats
administered the lower doses of antithrombin III (50 and 100 U/kg), but not
altered in those endotoxin-treated rats receiving 250 U/kg of antithrombin III.
These findings suggest that a higher antithrombin III dose is necessary to
prevent endothelial cell injury than is required to inhibit coagulation
abnormalities in an animal model of sepsis. These observations support the notion
that antithrombin III may prevent endotoxin-induced endothelial cell injury by
promoting endothelial release of prostaglandin I2 and thus inhibiting leukocyte
activation.
PMID- 9645918
TI - Postoperative plasma interleukin-6 in patients with renal cancer correlates with
C-reactive protein but not with total fibrinogen or with high molecular weight
fibrinogen fraction.
AB - The concentration of fibrinogen (Fb) and its fractions, the levels of interleukin
6 (I1-6), C-reactive protein (CRP), and immunoglobulin G (IgG) were determined in
38 patients operated on because of renal cancer. The increased Fb and I1-6
concentrations were found in approximately one-half of the patients with
malignancy. The relations among the high molecular weight (HMW) and two low
molecular weight (LMW and LMW') fibrinogen fractions in these patients before
surgery did not differ from the corresponding relations in normal subjects. The
levels of all (except IgG) compounds studied increased after surgery and the peak
of I1-6 was observed on the first postoperative day but that of CRP on the third
day. The concentrations of total Fb and of its HMW fraction were the highest also
on the third postoperative day and this was in contrast with the decline of low
molecular weight fractions at the same time. These variations of estimated
variables can be regarded as being relevant to the acute phase response. We have
noted a correlation between the maximal concentrations of I1-6 and CRP, but not
between the corresponding concentrations of Il-6 and total Fb or HMW Fb; this may
suggest that the concentration of Fb is also under the control of a factor other
than I1-6.
PMID- 9645919
TI - Factor II 20210 G-->A polymorphism associated to factor V Leiden: a report of two
thrombophilic families.
PMID- 9645920
TI - The Effect of the Simultaneous Addition of Molybdenum and Tungsten to the Culture
Medium on the Formate Dehydrogenase Activity from Methylobacterium sp. RXM
AB - Shake flask cultivation of the facultative methylotroph Methylobacterium sp. RXM
was carried out by using a statistical experimental design to investigate the
role of metal association on the formate dehydrogenase (FDH) levels. The maximal
values of FDH activity were obtained for tungsten concentration up to 0.6 uM and
for molybdenum concentration between 0.6 and 0.9 uM. The negative polynomial
parameter (beta2) for tungsten compared with the positive polynomial parameter
(beta1) for molybdenum on the FDH activity suggested that the latter metal exerts
a stronger influence on the enzyme stimulation than the tungsten metal. A
negative interaction between both metals was found, suggesting that tungsten and
molybdenum shared an antagonistic effect on the enzyme activity.
PMID- 9645923
TI - CO2 Emission in the 4-um Region.
AB - From spectra recorded at a resolution of 0.020 cm-1 of the flame CH4 + O2 at low
pressure, six new vibrational transitions in Deltav3 = 1 with 2v1 + v2 = 5 had
been recently identified [D. Bailly et al., J. Mol. Spectrosc. 182, 10-17 (1996)]
based on the HITRAN 92 predictions. New calculations have shown good consistency
with our assignments except for one transition, namely, (21(1)1)3e --> (21(1)0)3e
for which discrepancies (reaching 0.2 cm-1) were found. It has been possible to
resolve this issue using new emission spectra of CO2, vibrationally excited by
active nitrogen and recorded with a Fourier transform spectrometer at a
resolution of 6.3 x 10(-3) cm-1 in the 4-5 um spectral region. Copyright 1998
Academic Press.
PMID- 9645922
TI - TNF, apoptosis and autoimmunity: a common thread?
AB - A subset of cytokine mediators belonging to the tumor necrosis factor (TNF)
family cause apoptosis, acting through receptors and signaling pathways that have
recently come to light. Further, at least one autoimmune disease results from a
defined defect of apoptosis (mutations of the Fas ligand or its receptor). It is
offered that many, and perhaps most autoimmune diseases may result from primary
defects of apoptosis. Such defects may cause reflexive overproduction of TNF and
other pro-apoptotic cytokines. The collateral damage produced by these mediators
may be of pathogenetic importance in complex autoimmune disorders such as
rheumatoid arthritis and Crohn disease, wherein TNF blockade is known to have
ameliorative effects.
PMID- 9645924
TI - Nitrogen Broadening of Acetylene Lines in the nu5 Band at Low Temperature.
AB - N2-broadening coefficients have been measured for 22 lines of C2H2 at 173.4 K in
the P and R branches of the nu5 band, using a tunable diode-laser spectrometer.
The lines with J values ranging from 1 to 29 are located in the spectral range of
661-762 cm-1. The collisional widths obtained by Rautian profiles fitting closely
the measured spectral shape of the lines are slightly larger than those derived
from Voigt profiles. Semiclassical calculations of these broadenings have been
performed by considering, in addition to electrostatic interactions, successively
the atom-atom model and the Tipping-Herman intermolecular potential. The results
obtained, which for some of them are in good agreement with the experimental
data, depend significantly on the isotropic potential used to describe the
trajectory model. By comparing broadening coefficients at room and low
temperature, their temperature dependencies have been determined both
experimentally and theoretically Copyright 1998 Academic Press.
PMID- 9645925
TI - High-Resolution FTIR Study of the (nu3 + nu4, nu1 + nu4) Interacting System of
Rovibrational Bands of PF3 Between 1100 and 1300 cm-1
AB - With a resolution of 4.4 x 10(-3) cm-1, we were able to identify in this range
the very weak nu2 + 2nu04 (A1) component near 1180 cm-1, the nu3 + nu4 band
around 1205 cm-1 with its (A1 + A2) and E very intermixed components, and the nu1
+ nu4 (E) band centered at 1238 cm-1. Three thousand six hundred transitions
belonging to the (nu3 + nu4, nu1 + nu4) interacting system were fitted together
with a model taking into account l(2, 2) interactions inside nu1 + nu4 and
between (A1 + A2) and E components of nu3 + nu4, the l-vibrational resonance
inside nu3 + nu4(A1 + A2), and the Coriolis interactions between nu1 + nu4 and
nu3 + nu4(A1 + A2) on one hand and between nu1 + nu4 and nu3 + nu4 (E) on the
other. Four available MW transitions were also included in the fit. A rms of 0.76
x 10(-3) cm-1 was obtained with 34 free parameters among 38. Normally the Fermi
resonance, which links nu3 to nu2 + nu4 with a coupling term W234 = 2.86 cm-1,
must connect each component of nu3 + nu4 with each component of nu2 + 2nu4. But
since we have only little experimental information about the weak nu2 + 2nu04
component (120 assigned lines) and none about the dark nu2 + 2nu+/-24 component,
it was not possible to introduce this resonance in the fit. However, the
bandcenters' shifts were calculated since the basic coupling term W234 and the
anharmonic constant x24 are well known. Therefore, according to this
approximation, the very sensitive anharmonic constants x34 and g34 could be
deduced. Of course the x14 Fermi-independent constant, derived directly from the
(nu1 + nu4)0 bandcenter given by the fit, was certainly more accurate. Copyright
1998 Academic Press.
PMID- 9645926
TI - Electronic States and Spectra of BiO.
AB - The electronic spectrum of the BiO radical has been studied by Fourier transform
emission spectroscopy, laser-induced fluorescence, and excimer laser photolysis
techniques. Six new electronic states, A1 (Omega = 3/2) (Te = 11 528.8 cm-1,
omegae = 530.4 cm-1, omegaexe = 2.42 cm-1), G (Omega = 3/2) (Te = 20 273 cm-1,
omegae = 499 cm-1, omegaexe = 2.6 cm-1), H (Omega = 1/2) (Te = 20 469.76(6) cm-1,
omegae = 471.63(18) cm-1, omegaexe = 2.153(35) cm-1), I (Omega = 1/2) (Te = 21
982.50(2) cm-1, omegae = 506.50(11) cm-1, omegaexe = 3.263(34) cm-1), J (Omega =
3/2) (Te = 25 598.95(42) cm-1, omegae = 489.95(16) cm-1, omegaexe = 2.309(45) cm
1), and K (Omega = 1/2) (Te = 26 744.7(2) cm-1, omegae = 420.6(4) cm-1, omegaexe
= 5.25(5) cm-1), and 14 new electronic transitions (A1 <-- X1, G --> X2, H left
and right arrow X1, H --> A2(A), I left and right arrow X1, I --> A2, J left and
right arrow X1, J left and right arrow X2, K left and right arrow X1, K left and
right arrow X2, K --> A2, B left and right arrow X2, B --> A2, C left and right
arrow X2) have been detected. Time-resolved measurements of the fluorescence
decays have yielded the radiative lifetimes of the v = 0 levels of most states up
to <30 500 cm-1 energy (tauX2 = 480 +/- 100 us, tauA2 = 9.3 +/- 1.5 us, tauH = 15
+/- 3 us, tauI = 16 +/- 3 us, tauJ = 4.9 +/- 0.9 us, tauK = 2.6 +/- 0.3 us, tauB
= 0.55 +/- 0.08 us, tauC = 0.84 +/- 0.15 us) and rate constants for quenching of
the states by some rare gas atoms and simple molecules. The new electronic states
A1, G, H, I, J, and K and the previously known levels X1, X2, A2(A), B, C, and D
are assigned to spin-orbit states arising from low-energy valence configurations
of BiO with the help of detailed theoretical data calculated by Alekseyev et al.
(J. Chem. Phys. 100, 8956-8968 (1994)). Copyright 1998 Academic Press.
PMID- 9645927
TI - The Torsion-Inversion-Bending Energy Levels in the S1(n, pi*) Electronic State of
Acetaldehyde.
AB - The band assignments and analyses of the jet-cooled high-resolution laser-induced
fluorescence excitation spectrum of acetaldehyde that results from the S1(n, pi*)
electronic state have been extended to +600 cm-1 from the 0(0)0 system origin.
The new assignments start at Band #7 and finish at Band #21. Bands #8 and #9,
originally assigned to 14(2)0, have now been assigned to 15(3)0. The assignments
of the lower energy bands remain unaltered. The origins of the bands that involve
the torsional modes nu15 (v = 1 to 4) in combination with the wagging mode nu14
(v = 1 and 2) and the nu10 (v = 1) were determined by analyses with a rigid
rotational Hamiltonian. These origins were fitted to a set of levels that were
derived from a torsion-wagging-bending Hamiltonian that employed flexible large
amplitude coordinates. The resulting potential surface was found to have barriers
to torsion and inversion of 712.5 and 638.6 cm-1, respectively, with minima in
the potential hypersurface at theta = 59.9 degrees and alpha = 33.5 degrees for
the torsion and wagging coordinates. Copyright 1998 Academic Press.
PMID- 9645928
TI - Sub-Doppler Heterodyne Frequency Measurements on OCS Near 2900 cm-1 Using a CO
Overtone Sideband Spectrometer.
AB - We present sub-Doppler heterodyne frequency measurements on 10 rovibrational
transitions of carbonyl sulfide (OCS) between 2894 and 2910 cm-1. The
measurements were made using a CO overtone laser which had limited tuneability
through the generation of microwave sidebands in a CdTe crystal. With this
technique the laser frequencies were shifted to the desired OCS transition
frequencies. The transition frequencies could be measured with uncertainties less
than 30 kHz (Deltanu/nu = 3 x 10(-10)) by frequency offset-locking the CO
overtone laser to combination frequencies of two saturation-stabilized CO2 laser
standards. The measured transition frequencies of OCS were combined with previous
sub-Doppler, Fourier transform, and microwave measurements to recalculate
improved calibration tables for the 10(0)1-00(0)0, 11(1e)1-01(1e)0, and 11(1f)1
01(1f)0 bands. These tables are suitable for the calibration of infrared
spectrometers in the 87 THz region (near 2900 cm-1). Copyright 1998 Academic
Press.
PMID- 9645929
TI - The Far-Infrared Spectrum of ClNO2 Studied by High-Resolution Fourier-Transform
Spectroscopy.
AB - The far-infrared spectrum of nitryl chloride was studied using high-resolution
Fourier-transform spectroscopy in the 300-525 cm-1 region. Vibrational band
centers of fundamental, hot, and difference bands were determined. Furthermore,
rotational and centrifugal distortion constants up to fourth order for the nu3
bands of 35ClNO2 and 37ClNO2 (centered at 370 and 364 cm-1, respectively) were
obtained. The nu5 fundamental of ClNO2 (predicted around 410 cm-1) is very weak
and overlapped by difference bands. Copyright 1998 Academic Press.
PMID- 9645930
TI - Tunable Far-Infrared Spectroscopy of 82KrD+, 84KrD+, 86KrD+, and 82KrH+
AB - Pure rotational spectra of isotopic species of protonated krypton 82KrD+, 84KrD+,
86KrD+, and 82KrH+ were observed in the 0.75-3.5 THz region, using a tunable far
infrared radiation source. Rotational parameters B, D, and H of these molecular
ions were determined. By analyzing the observed frequencies with the previous
data on all the isotopic species, the mass independent Dunham parameters Ukl,
DeltaKrkl, and DeltaHkl have been improved. Copyright 1998 Academic Press.
PMID- 9645931
TI - Faraday Laser Magnetic Resonance Spectroscopy of Vibrationally Excited C2D.
AB - We studied the gas phase spectrum of the deuterated ethynyl radical C2D in the
region between 3196 and 3243 cm-1 using a Faraday LMR spectrometer in combination
with a CO overtone laser. The C2D radicals were generated in a dc glow discharge
containing helium, deuterium, and acetylene. We observed a hot band between two
vibronic 2Pi states with an origin at 3225 cm-1. The lower level is assigned to
the first excited bending level of the electronic X ground state. The upper level
corresponds to the first excited electronic state A at 3513 cm-1, which was
observed previously [J. Mol. Struct. 190, 41-60 (1988)]. This region is subject
to strong vibronic interaction, caused by mixing of the electronic X ground state
with the A state at 3513 cm-1. From the analysis of the spectra we could
determine the orbital g factor of the upper level, which gave important
information about the mixing ratios. In addition we were able to derive a precise
term value for the first excited bending level of the electronic X ground state.
The experimentally derived molecular parameters are compared with theoretically
calculated values, obtained by ab initio calculations. Copyright 1998 Academic
Press.
PMID- 9645932
TI - The High-Resolution Infrared Spectrum of the nu5 Band of Deuterated Formic Acid
(DCOOH).
AB - The Fourier transform infrared spectrum of the nu5 band of deuterated formic acid
(DCOOH) has been measured with a resolution of 0.004 cm-1 in the frequency range
of 1090-1180 cm-1. Using a Watson's A-reduced Hamiltonian in the Ir
representation, a total of 1731 assigned unperturbed transitions have been
analyzed to provide rovibrational constants for the upper state (v5 = 1) with a
standard deviation of 0.000363 cm-1. The band is A type with an unperturbed band
center at 1142.31075 +/- 0.00002 cm-1. The band is expected to be perturbed by a
nearby nu4 band through a Fermi resonance term and possibly a Coriolis term. The
resonance is particularly noticeable for Ka = 10, and 11, at high J values. About
215 perturbed lines were identified but they were not included in the final fit.
Copyright 1998 Academic Press.
PMID- 9645933
TI - Sub-Millimeter-Wave Spectroscopy of the Ar.H+3 and Ar.D+3 Ionic Complexes.
AB - An investigation of the sub-millimeter-wave spectra of the ionic complexes Ar.H+3
and Ar.D+3 is presented. These complexes were produced in a negative glow
electric discharge, in mixtures of argon with either H2 or D2. About 80 new
transitions were assigned in the 485-680 GHz frequency range using a sub
millimeter-wave spectrometer built with Russian made backward wave oscillators
(BWO) sources. These measurements enabled us to observe the first Ka = 2
transitions for Ar.H+3 and the first Ka = 3 transitions for Ar.D+3. Analyses of
the line frequencies were carried out using an IAM-like approach, which accounts
for the large amplitude internal rotation motion displayed by both species.
Insights into the geometry of the intermediate configuration for this large
amplitude motion were gained. Copyright 1998 Academic Press.
PMID- 9645934
TI - Diode Laser Spectroscopy in the 9.8-um nu14 Band of Benzene.
AB - High-resolution diode laser spectroscopy was applied to measure broadening
coefficients in the 9.8-um nu14 band of benzene, C6H6. Self-broadening was
investigated at 295 and 344 K for 73 lines between 1017.31 and 1045.85 cm-1 with
9 = J" = 66 and 1 = K" = 66. The measured self-broadening coefficients at
room temperature vary from 0.12 to 0.22 cm-1/atm (HWHM), whereas at 344 K the
self-broadening coefficients are in an interval between 0.07 cm-1/atm to 0.16 cm
1/atm. The Anderson-Tsao-Curnutte (ATC) theory was used to deduce the benzene
quadrupole moment and the b0 parameter from mean values of the broadening
coefficients at room temperature. It could be shown that the ATC theory is able
to describe the quantum number dependence and the absolute values of the self
broadening coefficients with sufficient accuracy. The collision partner
dependence of the broadening coefficients was measured for three Q-branch lines
in benzene mixtures with air, N2, He, Ne, Ar, Kr, and Xe. The results are
compared with similar experiments with NO2 and SO2 absorption lines with the
outcome that the qualitative change of the broadening coefficients with changing
collision partner is similar for all three molecular gases. Air broadening was
measured for additional five lines at both temperatures mentioned above. The
experimental setup and the data treatment are described in Part I of this article
(J. Mol. Spectrosc., 184, 433). Copyright 1998 Academic Press.
PMID- 9645935
TI - High-Resolution Laser Excitation Spectra of the A2Pi <-- X2Sigma+ System of SrBr:
The 0-0 and 1-0 Bands of Sr79Br and Sr81Br.
AB - Two bands (0-0 and 1-0) of the A2Pi-X2Sigma+ system of 88Sr79Br and 88Sr81Br have
been analyzed rotationally for the first time. Well-resolved spectra were
recorded by laser excitation spectroscopy with selective detection of
fluorescence. For each band of the individual isotopomers, about 130 line
positions with a measurement accuracy of approximately 0.003 cm-1 were employed
in a least-squares fit of the excited state molecular parameters. The principal
results for the A2Pi state are Ae = 302.432(1) cm-1 and Re = 2.7147(1) A.
Copyright 1998 Academic Press.
PMID- 9645936
TI - Hyperfine Constants and Nuclear Shieldings from the Microwave Spectra of FBO,
ClBO, and FBS.
AB - Rotational spectra of the unstable molecules FBO, ClBO, and FBS have been
measured in the 8-26 GHz frequency range using a pulsed jet cavity Fourier
transform microwave spectrometer. The samples were prepared by passing electric
discharges through mixtures of O2/BF3, O2/BCl3, or OCS/BF3, respectively,
entrained in Ne. Hyperfine structures in the observed transitions have been
resolved and analyzed in terms of nuclear quadrupole, spin-rotation, and spin
spin interactions. The quadrupole and spin-rotation coupling constants have been
used to show that the electronic environment surrounding the boron nucleus of all
three species is very similar. The spin-rotation constants have been used to
determine, for the first time, experimental average shieldings of the Cl, F, and
B nuclei of these molecules. Ab initio values for the nuclear shielding
parameters have been calculated for comparison. Copyright 1998 Academic Press.
PMID- 9645938
TI - EDITOR'S NOTE.
AB - Copyright
PMID- 9645939
TI - Characterisation of two articulins, the major epiplasmic proteins comprising the
membrane skeleton of the ciliate Pseudomicrothorax.
AB - Most protists possess a unique membrane skeleton, the epiplasm, which is involved
in pattern forming processes of the cell cortex and functions in maintaining cell
shape. Articulins, a novel class of cytoskeletal proteins, are major constituents
of the epiplasm. We have isolated cDNAs encoding the two major articulins of the
ciliate Pseudomicrothorax dubius. Peptide sequence data confirm the identity of
the cloned cDNAs encoding articulins 1 and 4. With the data presented here
sequence information for all major articulins of ciliates as well as the
distantly related euglenoids is available. Sequence comparison of the two newly
characterised ciliate articulins with the previously determined sequences of p60,
a minor articulin of the same species, and the two euglenoid articulins reveals
general sequence principles and uncovers new features of this protein family. The
hallmark of articulins is a central core domain of repetitive motifs of
alternating valine and proline residues, the VPV-motif. These VPV-motif repeats
are either 12-residues, or in some places, six residues long. Positively and
negatively charged residues segregate in register with valine and proline
positions. The VPV-motif is unique to articulins. The terminal domains flanking
the core are generally hydrophobic and contain a series of hexa- or heptapeptide
repeats rich in glycine and hydrophobic residues. The sequences of these short
repeats are very similar in articulins of the same species but are not conserved
between euglenoids and ciliates.
PMID- 9645940
TI - Chemotaxis of chinese hamster ovary cells expressing the human neutrophil formyl
peptide receptor: role of signal transduction molecules and alpha5beta1 integrin.
AB - Activation of the N-formyl peptide receptor (FPR) of human neutrophils by ligands
such as N-formyl-methionine-leucine-phenylalanine (fMLP) induces mobilization of
intracellular calcium, cell adhesion, chemotaxis, superoxide production and
degranulation. Chinese hamster ovary (CHO) cells are normally devoid of FPR and
unresponsive to fMLP, but when stably transfected with a human FPR cDNA,
exhibited some of these same responses. Specifically, stimulation with fMLP
resulted in release of intracellular calcium and chemotactic migration toward a
gradient of fMLP. As in neutrophils, both processes were inhibited through
receptor desensitization by prior exposure to a higher or equal concentration of
ligand or by treatment with pertussis toxin. Soluble and membrane-bound
fibronectin greatly increased fMLP-induced chemotaxis of CHO cells expressing
FPR, but not of wild-type CHO cells, suggesting a role for FPR in activation of
integrin function. Evidence for this hypothesis was obtained by demonstrating
that CHO cells expressing FPR rapidly increased their adhesion to a fibronectin
coated surface after stimulation with fMLP. Both chemotaxis and adhesion were
largely inhibited by RGDS peptide and a function-blocking antibody against alpha5
integrin. FPR-mediated chemotaxis of the CHO transfectants was partly inhibited
by a tyrosine kinase inhibitor, herbimycin A, and blocked by a phosphoinositide 3
kinase inhibitor, wortmannin. These data suggest that stimulation of CHO FPR
transfectants with a gradient of fMLP results in phosphoinositide 3-kinase
dependent chemotactic migration, which is enhanced by binding of activated
alpha5beta1 to fibronectin. This non-myeloid, non-lymphoid fibroblastic cell line
will thus serve as a useful model to investigate additional requirements of
signal transduction molecules, adhesion molecules and cytoskeletal elements in
FPR-mediated chemotaxis.
PMID- 9645941
TI - Initiation of skin basement membrane formation at the epidermo-dermal interface
involves assembly of laminins through binding to cell membrane receptors.
AB - To study the mechanism of basement membrane formation, we determined by
immunochemistry temporal and spatial expression of laminin-5 (Ln-5), laminin-1
(Ln-1) and their integrin receptors during early skin morphogenesis. A 3
dimensional skin culture was used that allows the study of the sequential
molecular events of basement membrane formation at the epidermodermal interface.
During early anchorage of keratinocytes to the extracellular matrix there is
expression of Ln-5, BP-230 antigen and alpha3, beta1 integrin subunits. During
epidermal stratification and prior to the formation of the lamina densa there is
assembly of Ln-5, Ln-1, collagen IV and nidogen accompanied by keratinocyte basal
clustering of alpha2, alpha3, alpha6, beta1, and beta4+ integrin subunits. The
assembly pattern of Ln-1 and Ln-5 can be disturbed with functional antibodies
against the beta1 (AIIB2) and alpha6 (GoH3) integrin subunits. Ln-1 assembly can
also be disturbed with antibodies against its E8 domain and by competitive
inhibition with a synthetic peptide (AG-73) derived from its G-4 domain.
Quantitative RT-PCR showed that the dermis contributes about 80% of the laminin
gamma)1 chain mRNA while 20% is produced by the epidermis which emphasizes its
dual tissue origin and the major contribution of the mesenchyma in laminin
production. The laminin gamma2 chain mRNA, present in Ln-5, was mostly of
epidermal origin. This study presents evidence that during the initiation of
basement membrane formation, laminins bind to keratinocyte plasma membrane
receptors and thus may serve as nucleation sites for further polymerization of
these compounds by a self-assembly process.
PMID- 9645942
TI - Molecular organization of the desmoglein-plakoglobin complex.
AB - Different epithelial intercellular junctions contain distinct complexes
incorporating plakoglobin. In adherens junctions, plakoglobin interacts with two
molecules, the transmembrane adhesion protein of the cadherin family (e.g. E
cadherin) and alpha-catenin. The latter is thought to anchor the cadherin
plakoglobin complex to the cortical actin cytoskeleton. In desmosomes,
plakoglobin forms a complex with desmosomal cadherins, either desmoglein (Dsg) or
desmocollin (Dsc), but not with alpha-catenin. To further understand the
structure and assembly of the plakoglobin-cadherin complexes we analyzed amino
acid residues involved in plakoglobin-Dsg interactions using alanine scanning
mutagenesis. Previously, we have shown that plakoglobin interacts with a 72 amino
acid-long cytoplasmic domain (C-domain) that is conserved among desmosomal and
classic cadherins. In this paper, we show that a row of the large hydrophobic
residues located at the C-terminal portion of the Dsg C-domain is indispensable
for interaction with plakoglobin. To study a reciprocal site we expressed
plakoglobin (MPg) or its mutants tagged by 6 myc epitope in epithelial A-431
cells. Using sucrose gradient centrifugation and subsequent co
immunoprecipitation, MPg was found to be efficiently incorporated into the same
type of complexes as endogenous plakoglobin. A major pool of Dsg-plakoglobin
complexes sedimented at 8S and exhibited a 1:1 stoichiometry. Using alanine
scanning mutagenesis and the co-immunoprecipitation assay we identified nine
hydrophobic amino acids within the arm repeats 1-3 of plakoglobin, that are
required for binding to Dsg and Dsc. Eight of these amino acids also participate
in the interaction with alpha-catenin. No mutations were found to reduce the
affinity of plakoglobin binding to E-cadherin. These data provide direct evidence
that the same hydrophobic plakoglobin surface is essential for mutually exclusive
interaction with distinct proteins such as alpha-catenin and desmosomal
cadherins.
PMID- 9645943
TI - A rod end deletion in the intermediate filament protein nestin alters its
subcellular localization in neuroepithelial cells of transgenic mice.
AB - Neuroepithelial and radial glial cells span between the ventricular and the pial
surfaces of the neural tube and express two intermediate filaments (IFs), nestin
and vimentin, which form a filamentous network throughout the length of the
cells. In this report we study the polymerization characteristics of nestin and
examine how mutations affect the assembly and localization of the nestin protein
in cultured cells and in the developing CNS of transgenic mice. A wild-type rat
nestin gene transfected into the IF-free SW13 cell line failed to assemble into a
filamentous network but was incorporated into the existing IF network of a
subclone expressing vimentin, demonstrating that nestin requires vimentin for
proper assembly. In transgenic mice, rat nestin formed a network
indistinguishable from that formed by endogenous nestin and vimentin, but a
mutant form lacking five amino acids at the carboxy terminus of the rod domain
was largely restricted to the pial endfeet. Since nestin mRNA is localized to the
pial endfoot region we propose that both transgenes are translated there, but
that the wild-type protein is preferentially incorporated into the IF network.
These observations provide evidence for hierarchical assembly and a complex
organization of the IF network along the ventricular-pial axis in the early CNS.
PMID- 9645944
TI - Functional association of nuclear protein 4.1 with pre-mRNA splicing factors.
AB - Protein 4.1 is a multifunctional polypeptide that links transmembrane proteins
with the underlying spectrin/actin cytoskeleton. Recent studies have shown that
protein 4.1 is also present in the nucleus, localized in domains enriched in
splicing factors. Here we further analyze the relationship between protein 4. 1
and components of the splicing machinery. Using HeLa nuclear extracts capable of
supporting the splicing of pre-mRNAs in vitro, we show that anti-4.1 antibodies
specifically immunoprecipitate pre-mRNA and splicing intermediates.
Immunodepletion of protein 4.1 from HeLa nuclear extracts results in inhibition
of their splicing activity, as assayed with two different pre-mRNA substrates.
Coprecipitation of protein 4.1 from HeLa nuclear extracts with proteins involved
in the processing of pre-mRNA further suggests an association between nuclear
protein 4.1 and components of the splicing apparatus. The molecular cloning of a
4.1 cDNA encoding the isoform designated 4.1E has allowed us to show that this
protein is targeted to the nucleus, that it associates with the splicing factor
U2AF35, and that its overexpression induces the redistribution of the splicing
factor SC35. Based on our combined biochemical and localization results, we
propose that 4.1 proteins are part of nuclear structures to which splicing
factors functionally associate, most likely for storage purposes.
PMID- 9645945
TI - PDGF induces reorganization of vimentin filaments.
AB - In this study we demonstrate that stimulation with platelet-derived growth factor
(PDGF) leads to a marked reorganization of the vimentin filaments in porcine
aortic endothelial (PAE) cells ectopically expressing the PDGF beta-receptor.
Within 20 minutes after stimulation, the well-spread fine fibrillar vimentin was
reorganized as the filaments aggregated into a dense coil around the nucleus. The
solubility of vimentin upon Nonidet-P40-extraction of cells decreased
considerably after PDGF stimulation, indicating that PDGF caused a redistribution
of vimentin to a less soluble compartment. In addition, an increased tyrosine
phosphorylation of vimentin was observed. The redistribution of vimentin was not
a direct consequence of its tyrosine phosphorylation, since treatment of cells
with an inhibitor for the cytoplasmic tyrosine kinase Src, attenuated
phosphorylation but not redistribution of vimentin. These changes in the
distribution of vimentin occurred in conjunction with reorganization of actin
filaments. In PAE cells expressing a Y740/751F mutant receptor that is unable to
bind and activate phosphatidylinositol 3'-kinase (PI3-kinase), the distribution
of vimentin was virtually unaffected by PDGF stimulation. Thus, PI3-kinase is
important for vimentin reorganization, in addition to its previously demonstrated
role in actin reorganization. The small GTPase Rac has previously been shown to
be involved downstream of PI3-kinase in the reorganization of actin filaments. In
PAE cells overexpressing dominant negative Rac1 (N17Rac1), no change in the fine
fibrillar vimentin network was seen after PDGF-BB stimulation, whereas in PAE
cells overexpressing constitutively active Rac1 (V12Rac1), there was a dramatic
change in vimentin filament organization independent of PDGF stimulation. These
data indicate that PDGF causes a reorganization of microfilaments as well as
intermediate filaments in its target cells and suggest an important role for Rac
downstream of PI3-kinase in the PDGF stimulated reorganization of both actin and
vimentin filaments.
PMID- 9645946
TI - Expression and characterization of splice variants of PYK2, a focal adhesion
kinase-related protein.
AB - Focal adhesion kinase and the recently identified proline-rich tyrosine kinase 2
(PYK2), also known as cell adhesion kinase &bgr ;, related adhesion focal
tyrosine kinase or calcium-dependent protein tyrosine kinase, define a new family
of non-receptor protein tyrosine kinases. Activation of PYK2 has been implicated
in multiple signaling events, including modulation of ion channels, T- and B-cell
receptor signaling and cell death. Mechanisms underlying the functional diversity
of PYK2 are unclear. Here, we provide evidence for two novel alternatively
expressed isoforms of PYK2. One isoform, designated PYK2s (PYK2 splice form),
appears to be a splice variant of PYK2 lacking 42 amino acids within the C
terminal domain. A second isoform, referred to as PRNK (PYK2-related non-kinase),
appears to be specified by mRNAs that encode only part of the C-terminal domain
of PYK2. Northern blot analysis indicates that the unspliced PYK2 is expressed at
high levels in the brain and poorly expressed in the spleen, whereas PYK2s and
PRNK are expressed in the spleen. In situ hybridization studies of rat brain
demonstrate that the unspliced PYK2 is selectively expressed at high levels in
hippocampus, cerebral cortex and olfactory bulb, whereas PYK2s and PRNK are
expressed at low levels in all regions of rat brain examined. Immunofluorescence
analysis of ectopically expressed PRNK protein shows that PRNK, in contrast to
full-length PYK2, is localized to focal adhesions by sequences within the focal
adhesion targeting domain. In addition, PYK2, but not PRNK, interacts with
p130(cas )and Graf. These results imply that PRNK may selectively regulate PYK2
function in certain cells by binding to some but not all PYK2 binding partners,
and the functional diversity mediated by PYK2 may be due in part to complex
alternative splicing.
PMID- 9645947
TI - Human colonic cancer cells synthesize and adhere to laminin-5. Their adhesion to
laminin-5 involves multiple receptors among which is integrin alpha2beta1.
AB - In the mature gut, laminin-5 is expressed at the basal aspect of the
differentiating epithelial cells. In vitro, we show that three more or less
differentiated human colonic cancer HT29 cell lines produce and deposit laminin
5; they predominantly synthesize and secrete the 440 kDa form of laminin-5 that
comprises the unprocessed 155 kDa gamma2 chain, as determined by
immunoprecipitation analysis. In contrast, the highly differentiated colon
carcinoma Caco-2 cells produce almost no laminin-5. Using anti-integrin
antibodies, we show that adhesion of the two colonic cancer cell lines to laminin
5 is mediated by multiple integrin receptors including those for alpha3beta1,
alpha6beta1 and alpha6beta4 integrins like in other cell types. In addition, the
implication of integrin alpha2beta1 in this adhesion process is demonstrated for
the first time. This has been shown by cell adhesion inhibition experiments,
solid phase assays and confocal analysis. Together with previous in situ
observations, these data provide a baseline knowledge for the understanding of
the regulation of laminin-5 in normal and pathological intestine.
PMID- 9645948
TI - Radial F-actin arrays precede new hypha formation in Saprolegnia: implications
for establishing polar growth and regulating tip morphogenesis.
AB - The roles of cortical F-actin in initiating and regulating polarized cell
expansion in the form of hyphal tip morphogenesis were investigated by analyzing
long term effects of F-actin disruption by latrunculin B in the oomycete
Saprolegnia ferax, and detecting localized changes in the cortical F-actin
organization preceding hyphal formation. Tubular hyphal morphology was dependent
on proper F-actin organization, since latrunculin induced dose-dependent actin
disruption and corresponding changes in hyphal morphology and wall deposition.
With long incubation times (1 to 3 hours), abundant subapical expansion occurred,
the polar form of which was increasingly lost with increasing actin disruption,
culminating in diffuse subapical expansion. These extreme effects were
accompanied by disorganized cytoplasm, and novel reorganization of microtubules,
characterized by star-burst asters. Upon removing latrunculin, hyperbranching
produced abundant polar branches with normal F-actin organization throughout the
colony. The results are consistent with F-actin regulating polar vesicle delivery
and controlling vesicle fusion at the plasma membrane, and suggest that F-actin
participates in establishing polar growth. To test this idea further, we utilized
the hyperbranching growth form of Saprolegnia. Early during the recovery time,
prior to multiple branch formation, radial arrays of filamentous F-actin were
observed in regions with no detectable surface protrusion. Their locations were
consistent with those of the numerous branches that formed with longer recovery
times. Similar radial arrays preceded germ tube formation in asexual spores. The
arrays were important for initiating polar growth since the spores lost their
ability to polarize when the F-actin was disrupted with latrunculin, and
increased isometrically in size rather than producing germ tubes. Therefore, F
actin participates in initiating tip formation in addition to its previously
demonstrated participation in maintenance of hyphal tip growth. The cortical
location and radial organization of the arrays suggest that they recruit and
stabilize membrane-bound and cytosolic factors required to build a new tip.
PMID- 9645949
TI - cyk-1: a C. elegans FH gene required for a late step in embryonic cytokinesis.
AB - A maternally expressed Caenorhabditis elegans gene called cyk-1 is required for
polar body extrusion during meiosis and for a late step in cytokinesis during
embryonic mitosis. Other microfilament- and microtubule-dependent processes
appear normal in cyk-1 mutant embryos, indicating that cyk-1 regulates a specific
subset of cytoskeletal functions. Because cytokinesis initiates normally and
cleavage furrows ingress extensively in cyk-1 mutant embryos, we propose that the
wild-type cyk-1 gene is required for a late step in cytokinesis. Cleavage furrows
regress after completion of mitosis in cyk-1 mutants, leaving multiple nuclei in
a single cell. Positional cloning and sequence analysis of the cyk-1 gene reveal
that it encodes an FH protein, a newly defined family of proteins that appear to
interact with the cytoskeleton during cytokinesis and in the regulation of cell
polarity. Consistent with cyk-1 function being required for a late step in
embryonic cytokinesis, we show that the CYK-1 protein co-localizes with actin
microfilaments as a ring at the leading edge of the cleavage furrow, but only
after extensive furrow ingression. We discuss our findings in the context of
other studies suggesting that FH genes in yeast and insects function early in
cytokinesis to assemble a cleavage furrow.
PMID- 9645950
TI - Interphase-specific association of intrinsic centromere protein CENP-C with
HDaxx, a death domain-binding protein implicated in Fas-mediated cell death.
AB - CENP-C, one of the few known intrinsic proteins of the human centromere, is
thought to play structural as well as regulatory roles crucial to proper
chromosome segregation and mitotic progression. To further define the functions
of CENP-C throughout the cell cycle we have used the yeast interaction trap to
identify proteins with which it interacts. One specific CENP-C interactor, which
we have named HDaxx, was characterized in detail and found to be homologous to
murine Daxx, a protein identified through its ability to bind the death domain of
Fas (CD95). The interaction between CENP-C and HDaxx is mediated by the amino
terminal 315 amino acids of CENP-C and the carboxyl-terminal 104 amino acids of
HDaxx. This region of Daxx is responsible for binding to death domains of several
apoptosis signalling proteins. The biological significance of the interaction
between CENP-C and HDaxx was confirmed by immunofluorescence colocalization of
these two proteins at discrete spots in the nuclei of some interphase HeLa cells.
We discuss the functional implications of the interphase-restricted association
of HDaxx with centromeres.
PMID- 9645951
TI - Distinct subcellular localization of calcium binding S100 proteins in human
smooth muscle cells and their relocation in response to rises in intracellular
calcium.
AB - Changes in cytosolic Ca2+ concentration control a wide range of cellular
responses, and intracellular Ca2+-binding proteins are the key molecules to
transduce Ca2+ signaling via interactions with different types of target
proteins. Among these, S100 Ca2+-binding proteins, characterized by a common
structural motif, the EF-hand, have recently attracted major interest due to
their cell- and tissue-specific expression pattern and involvement in various
pathological processes. The aim of our study was to identify the subcellular
localization of S100 proteins in vascular smooth muscle cell lines derived from
human aorta and intestinal smooth muscles, and in primary cell cultures derived
from arterial smooth muscle tissue under normal conditions and after stimulation
of the intracellular Ca2+ concentration. Confocal laser scanning microscopy was
used with a specially designed colocalization software. Distinct intracellular
localization of S100 proteins was observed: S100A6 was present in the
sarcoplasmic reticulum as well as in the cell nucleus. S100A1 and S100A4 were
found predominantly in the cytosol where they were strongly associated with the
sarcoplasmic reticulum and with actin stress fibers. In contrast, S100A2 was
located primarily in the cell nucleus. Using a sedimentation assay and subsequent
electron microscopy after negative staining, we demonstrated that S100A1 directly
interacts with filamentous actin in a Ca2+-dependent manner. After thapsigargin
(1 microM) induced increase of the intracellular Ca2+ concentration, specific
vesicular structures in the sarcoplasmic reticulum region of the cell were formed
with high S100 protein content. In conclusion, we demonstrated a distinct
subcellular localization pattern of S100 proteins and their interaction with
actin filaments and the sarcoplasmic reticulum in human smooth muscle cells. The
specific translocation of S100 proteins after intracellular Ca2+ increase
supports the hypothesis that S100 proteins exert several important functions in
the regulation of Ca2+ homeostasis in smooth muscle cells.
PMID- 9645952
TI - Vesicle-associated brain myosin-V can be activated to catalyze actin-based
transport.
AB - Myosin-V has been linked to actin-based organelle transport by a variety of
genetic, biochemical and localization studies. However, it has yet to be
determined whether myosin-V functions as an organelle motor. To further
investigate this possibility, we conducted a biochemical and functional analysis
of organelle-associated brain myosin-V. Using the initial fractionation steps of
an established protocol for the purification of brain myosin-V, we isolated a
population of brain microsomes that is approx. fivefold enriched for myosin-V,
and is similarly enriched for synaptic vesicle proteins. As demonstrated by
immunoelectron microscopy, myosin-V associates with 30-40% of the vesicles in
this population. Although a majority of myosin-V-associated vesicles also label
with the synaptic vesicle marker protein, SV2, less than half of the total SV2
positive vesicles label with myosin-V. The average size of myosin-V/SV2 double
labeled vesicles (90+/-45 nm) is larger than vesicles that label only with SV2
antibodies (60+/-30 nm). To determine if these vesicles are capable of actin
based transport, we used an in vitro actin filament motility assay in which
vesicles were adsorbed to motility assay substrates. As isolated, the myosin-V
associated vesicle fraction was nonmotile. However, vesicles pre-treated with ice
cold 0.1% Triton X-100 supported actin filament motility at rates comparable to
those on purified myosin-V. This dilute detergent treatment did not disrupt
vesicle integrity. Furthermore, while this treatment removed over 80% of the
total vesicle proteins, myosin-V remained tightly vesicle-associated. Finally,
function-blocking antibodies against the myosin-V motor domain completely
inhibited motility on these substrates. These studies provide direct evidence
that vesicle-associated myosin-V is capable of actin transport, and suggest that
the activity of myosin-V may be regulated by proteins or lipids on the vesicle
surface.
PMID- 9645953
TI - Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL
1beta expression resulting in chondrogenesis in mouse embryonic limb bud
mesenchymal cells.
AB - The initial modeling and subsequent development of the skeleton is controlled by
complex gene-environment interactions. Biomechanical forces may be one of the
major epigenetic factors that determine the form and differentiation of skeletal
tissues. In order to test the hypothesis that static compressive forces are
transduced into molecular signals during early chondrogenesis, we have developed
a unique three-dimensional collagen gel cell culture system which is permissive
for the proliferation and differentiation of chondrocytes. Mouse embryonic day 10
(E10) limb buds were microdissected and dissociated into cells which were then
cultured within a collagen gel matrix and maintained for up to 10 days. Static
compressive forces were exerted onto these cultures. The time course for
expression pattern and level for cartilage specific markers, type II collagen and
aggrecan, and regulators of chondrogenesis, Sox9 and IL-1beta, were analyzed and
compared with non-compressed control cultures. Under compressive conditions,
histological evaluation showed an apparent acceleration in the rate and extent of
chondrogenesis. Quantitatively, there was a significant 2- to 3-fold increase in
type II collagen and aggrecan expression beginning at day 5 of culture and the
difference was maintained through 10 days of cultures. Compressive force also
causes an elevated level of Sox9, a transcriptional activator of type II
collagen. In contrast, the expression and accumulation of IL-1beta, a
transcriptional repressor of type II collagen was down-regulated. We conclude
that static compressive forces promote chondrogenesis in embryonic limb bud
mesenchyme, and propose that the signal transduction from a biomechanical stimuli
can be mediated by a combination of positive and negative effectors of cartilage
specific extracellular matrix macromolecules.
PMID- 9645954
TI - Proopiomelanocortin (POMC) mRNA expression: distribution and region-specific down
regulation by chronic morphine in female guinea pig hypothalamus.
AB - There is compelling evidence that endogenous opioid peptides are regulated by
exogenous opiates. Our previous studies have shown that the mu-opioid receptor
protein and mRNA are down-regulated in the mediobasal hypothalamus of the female
guinea pig following chronic morphine treatment. In addition,
electrophysiological studies have shown that hypothalamic beta-endorphin (beta
EP) neurons express mu-opioid receptors that are uncoupled and down-regulated
following chronic morphine treatment. Currently, we tested the hypothesis that
chronic morphine, which produces down-regulation of mu-opioid receptors, causes a
down-regulation of pro-opiomelanocortin (POMC, the precursor of beta-EP) mRNA
expression in female guinea pig hypothalamus. Female guinea pigs were
ovariectomized and implanted subcutaneously (s.c.) with 4 x 75 mg pellets for 2
days plus six more pellets of either morphine (n = 6) or placebo (n = 6) for
another 5 days. Animals were sacrificed between 1000 and 1100 h on day 7. The
expression of POMC mRNA were investigated using in situ hybridization
histochemistry with a guinea pig specific 35S-labeled cRNA probe in hypothalamic
tissue sections. POMC mRNA was localized to the arcuate nucleus (Arc) and median
eminence (ME) of the medial basal hypothalamus. The distribution pattern was the
same in both morphine and placebo control animals. However, the density of silver
grains was less in morphine treated animals versus placebo control animals.
Overall, the level of POMC mRNA was decreased by 22% in the Arc of morphine
treated guinea pigs as compared with the placebo controls (p < 0.05). This
decrease in POMC mRNA expression was even greater in the caudal Arc (28%, p <
0.01) in morphine-treated animals. These results suggested that the biosynthetic
activity of POMC neurons is down-regulated with chronic exposure to morphine.
PMID- 9645955
TI - Temporal changes in gene expression following cryogenic rat brain injury.
AB - Expression of 18 genes was examined at 8 different time points between 1 h and 28
days following cryogenic rat brain injury. The genes include thymidine kinase
(TK), p53 tumor suppressor, c-fos, renin, myelin basic protein (MBP), proteolipid
protein (PLP), transferrin, transferrin receptor, platelet-derived growth factor
A (PDGF A), platelet-derived growth factor B (PDGF B), platelet-derived growth
factor receptor alpha (PDGF alpha receptor), platelet-derived growth factor
receptor beta (PDGF beta receptor), glial fibrillary acidic protein (GFAP),
transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor
(bFGF), fibroblast growth factor receptor-1 (FGF-R1), insulin-like growth factor
1 (IGF-1), and somatostatin. Time courses of gene expression were determined for
RNAs derived from hippocampus and cortex. Genes were divided into categories
based upon those in which statistically significant changes in expression were
first observed at or before 24 h (early genes) and those in which changes were
first observed at or after 72 h (late genes). In the present model, many genes
demonstrate elevated RNA levels in the cortex prior to hippocampus, following
injury. RNAs transcribed from late genes tend to be elevated concurrently in
cortex and hippocampus.
PMID- 9645956
TI - BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B
in cortical and hippocampal postsynaptic densities.
AB - While neurotrophins are critical for neuronal survival and differentiation,
recent work suggests that they acutely regulate synaptic transmission as well.
Brain-derived neurotrophic factor (BDNF) enhances excitatory postsynaptic
currents in cultured dissociated hippocampal neurons within 2-3 min through
postsynaptic, phosphorylation-dependent mechanisms. Moreover, BDNF modulates
hippocampal long-term potentiation, in which postsynaptic NMDA (N-methyl-D
aspartate) receptors (NRs) play a key role. We now report that BDNF acutely
increases tyrosine phosphorylation of the specific NMDA receptor subunit NR2B,
which has recently been shown to play a role in long-term potentiation.
Incubation of BDNF with cortical or hippocampal postsynaptic densities for 5 min
increased tyrosine phosphorylation of the NR2B subunits in a dose-dependent
manner. A maximal increase to 165% of control phosphorylation occurred at a BDNF
concentration of 2 ng/ml. The BDNF action appeared to be specific, since nerve
growth factor, another member of the neurotrophin gene family, had no effect on
NR2B phosphorylation. Further, BDNF action was selective, since it did not alter
tyrosine phosphorylation of NR2A subunits. Our results suggest that tyrosine
phosphorylation of NR2B subunits of the NMDA receptor may contribute to
neurotrophin modulation of postsynaptic responsiveness and long-term
potentiation.
PMID- 9645957
TI - Granule cell development in the cerebellum is punctuated by changes in Sox gene
expression.
AB - Development of the vertebrate cerebellum is unusual compared to most other
regions of the brain since it involves two germinal regions. Most cell types
arise from the luminal, ventricular zone as in other brain regions, but granule
cells arise from the second germinal layer, the external granular layer (EGL).
Our analysis of the temporal and positional expression of three members of the
Sox gene family of transcription factors in the cerebellum shows that granule
cell development is unusual compared to most other neurons of the central nervous
system (CNS). We show that granule cell precursors lose expression of cSox2 and
cSox3 as they migrate to form the EGL. The EGL is the first example of a germinal
layer in the CNS which does not exhibit expression of these genes. Throughout
most of the CNS cSox11 expression is very low in the ventricular zone but
increases dramatically as cells cease proliferation and migrate to form the
subventricular zone. We also find that cSox11 expression increases when cells of
the cerebellum migrate to form the EGL, but levels of expression as high as that
in the subventricular zone are only seen when cells cease proliferation and
migrate inwards to form the deep EGL. These observations demonstrate that cells
of the proliferative superficial EGL differ qualitatively from cells of the
ventricular zone in their expression of Sox genes whereas the post-proliferative
cells of the deep EGL appear analogous, in their expression of Sox genes, to
cells of the subventricular zone.
PMID- 9645958
TI - Enhancement of beta-amyloid precursor protein transcription and expression by the
soluble interleukin-6 receptor/interleukin-6 complex.
AB - We investigated a potential role for the soluble interleukin-6 receptor (sIL-6R)
in modulating interleukin-6 (IL-6) function in the central nervous system by
assessing IL-6 and sIL-6R effects on beta-amyloid precursor protein (beta-APP)
transcription and expression in cells of human neuronal origin. Cells transfected
with a luciferase reporter plasmid containing a 3.8 kb DNA fragment of the beta
APP promoter were shown to have inducible promoter activity when treated with
phorbol ester or basic fibroblast growth factor, but not when treated with
lipopolysaccharide or Il-6. PCR amplification analysis revealed the presence of
mRNA encoding the signaling subunit of the Il-6 receptor complex, the gp130
subunit, at levels approximating that found in human cortical tissue. The mRNA
encoding the IL-6 receptor, however, was poorly expressed and was detectable only
at high amplification cycles. When purified sIL-6R protein was added together
with IL-6, there was a rapid induction of promoter activity within 2 h of
stimulation followed by elevations in protein levels of both cell-associated and
secreted beta-APP. Analysis of mRNA transcripts from human cortical brain tissue
and cell cultures derived from fetal human brain demonstrated the presence of an
alternatively spliced secreted form of the IL-6 receptor mRNA, suggesting that
cells of the central nervous system may themselves be a source of sIL-6R protein.
The capacity for sIL-6R to enhance IL-6 function and broaden the IL-6 target cell
population in the brain has implications for the regulation of beta-APP
expression in disease states such as Alzheimer's disease where elevations in
brain IL-6 levels have been reported.
PMID- 9645959
TI - Complex expression pattern of the SCO-spondin gene in the bovine subcommissural
organ: toward an explanation for Reissner's fiber complexity?
AB - Bovine SCO-spondin is a glycoprotein secreted by the subcommissural organ (SCO),
an ependymal derivative located in the roof of the third ventricle. It shows
homology with developmental molecules involved in directional axonal growth.
Using SCO-spondin cDNAs as probes, we analysed the specific expression of the
corresponding gene in the bovine SCO by Northern blot and in situ hybridization
(ISH). A strong expression was detected in the secretory ependymal and hypendymal
cells of the SCO and the main transcripts showed a large size 14 kb. A single
copy gene was revealed by Southern blot analysis of bovine genomic DNA. The
presence of additional transcripts suggested a transcriptional regulation of the
SCO-spondin gene. A comparative analysis of the results obtained by molecular and
immunological techniques (immunoblotting and immunopurification) pointed to the
presence of several SCO-spondin related proteins in the SCO encoded by the same
gene. The presence in the cerebral hemispheres (CH) of a 54-kDa glycoprotein with
a common epitope is discussed as a putative cleaved SCO-spondin product carried
by the cerebrospinal fluid, that may act on neuronal development.
PMID- 9645960
TI - Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA
following kainic acid-induced limbic seizure.
AB - Expression of mRNA for glutamate-aspartate transporter (GLAST/GluT-1/EAAT1) was
studied in the brain of the rat which presented recurrent limbic seizure
following systemic administration of kainic acid (KA) by in situ hybridization
and Northern blot analysis. The expression of GLAST mRNA was markedly increased
after 12 h and peaked after 48 h in animals which demonstrated limbic seizure.
The induction of the mRNA were observed in the small non-neuronal cells in the
hippocampus, especially around CA3 region and hilus. In contrast, there was no
change in GLAST mRNA levels in KA injected seizure-free animals. These findings
suggest that GLAST mRNA is induced by seizure and increased extracellular
glutamate levels during seizure may be important for induction of GLAST mRNA.
PMID- 9645961
TI - CBF/NF-Y activates transcription of the human tryptophan hydroxylase gene through
an inverted CCAAT box.
AB - The human tryptophan hydroxylase gene (hTPH) encodes the rate-limiting enzyme in
the biosynthesis of serotonin, a neurotransmitter which has been implicated in a
number of psychiatric illnesses. This enzyme is expressed in a tissue-specific
manner. We examined the transcriptional activity of a series of 5' deletion
promoter-reporter constructs extending from nucleotide (nt) -1954 to +40 and
found that the region between nt -163 and +40 contains a regulatory element
important for efficient transcription of the gene, DNase I footprint analyses,
using P815-HTR and HeLa nuclear protein extracts, revealed a single prominent
footprint between nt -78 and -44. A cis-acting element in the footprint region
was identified as an inverted CCAAT box (-67 ATTGG -63) by gel shift assays. Two
base pair (bp) mutations in the core CCAAT sequence eliminated protein binding in
gel shift assays and reduced transcriptional activity approximately 50% in
transient transfection assays. Competitive gel shift assays showed that the
protein binding to the hTPH CCAAT box was effectively competed by an
oligonucleotide (oligo) harboring a binding site for CCAAT box binding factor
(CBF)/nuclear factor-Y (NF-Y). A selective antibody against the B subunit of
CBF/NF-Y supershifted the protein-DNA complex formed between the -90/-50 oligo
probe and nuclear protein extracts. Our results indicate that the binding of
CBF/NF-Y to the inverted CCAAT box is responsible for transcriptional activation
of the nTPH gene.
PMID- 9645962
TI - Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor
alpha (CNTFR alpha) expression following focal cerebral ischemia.
AB - Ciliary neurotrophic factor (CNTF) is a member of cytokines, with trophic effects
on ciliary, motor sympathetic, sensory, retinal and hippocampal neurons. In the
present study, we examined the temporal and spatial expression profiles of CNTF
and CNTF receptor alpha (CNTFR alpha) mRNAs in a focal cerebral ischemia model
induced by transient occlusion of the right middle cerebral artery and both
common carotid arteries. Northern blot analysis showed a slow and sustained
increase in the 1.2 kb transcript of CNTF mRNA in the ischemic cortex of rats
subjected to a transient 60 min ischemic insult. A delayed decrease in the 2.1 kb
transcript of CNTFR alpha mRNA in the ischemic cortex was observed in rats
subjected to 60 min ischemia followed by 72 h of reperfusion. In situ
hybridization studies revealed constitutive expression of CNTFR alpha mRNA in the
majority of neurons in the brain. Following 4 h of reperfusion, increased
expression of CNTFR alpha mRNA was observed in the ipsilateral dentate gyrus,
which is opposite to the down-regulation noted in the ischemic cortex. Within the
infarct area CNTFR alpha mRNA had a marked increase in cortical layer II but a
decrease in cortical layer V following 1 day of reperfusion. No signal of CNTFR
alpha mRNA was detected within the infarct region following 3 days of
reperfusion. Following 1 week of reperfusion, although no marked changes was
observed in the level of CNTFR alpha mRNA in the area immediately surrounding the
necrosis region where the reactive astrocytes were noted, a striking increase in
the CNTF mRNA signal was noted. In summary, differential regulation of CNTF and
CNTFR alpha mRNAs was noted in the ischemic cortex. Regional differences in CNTF
receptor expression were noted between the ischemic cortex and ipsilateral
dentate gyrus as well as between cortical layer II and V within the infarct
region. CNTF mRNA, but not CNTFR alpha mRNA, had a marked increase in the area
immediately adjacent to the necrosis. The mechanisms and patho-physiological
significance for these differential regulation remain to be studied.
PMID- 9645963
TI - Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression
in rat hippocampus.
AB - Activity-induced brain-derived neurotrophic factor (BDNF) expression is
negatively modulated by circulating adrenal steroids. The rat BDNF gene gives
rise to four major transcript forms that each contain a unique 5' exon (I-IV) and
a common 3' exon (V) that codes for BDNF protein. Exon-specific in situ
hybridization was used to determine if adrenalectomy has differential effects on
basal and activity-induced BDNF transcript expression in hippocampus.
Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight
increases in exon III-containing mRNA with 7-10-day survival and in exon II
containing mRNA with 30-days survival. In the dentate gyrus granule cells,
adrenalectomy markedly potentiated increases in exon I and II cRNA labeling, but
not increases in exon III and IV cRNA labeling, elicited by one hippocampal
afterdischarge. Similarly, for the granule cells and CA1 pyramidal cells, hilus
lesion (HL)-induced recurrent limbic seizures elicited greater increases in exon
I and II cRNA hybridization in adrenalectomized (ADX) as compared to adrenal
intact rats. In this paradigm, adrenalectomy modestly potentiated the increase in
exon III-containing mRNA in CA1 but had no effect on exon IV-containing mRNA
content. These results demonstrate that the negative effects of adrenal hormones
on activity-induced BDNF expression are by far the greatest for transcripts
containing exons I and II. Together with evidence for region-specific transcript
expression, these results suggest that the effects of stress on adaptive changes
in BDNF signalling will be greatest for neurons that predominantly express
transcripts I and II.
PMID- 9645964
TI - Regulation of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2 gene
transcript in neuronal cells.
AB - The sarco/endoplasmic reticulum Ca(2+)-transport ATPase (SERCA2) pre-mRNA is
alternatively processed in a tissue-specific manner. At its 3' end, two 5' splice
donor sites compete for the same 3' acceptor splice site (3'A). While the
upstream 5' donor splice site (5'D1) is used in muscle cells giving rise to the
class 1 mRNA, the downstream one (5'D2) is exclusively used in neuronal cells
generating the class 4 mRNA. Using a neuroblastoma cell line and a minigene
containing the 3' end of the SERCA2 gene, we have investigated the regulation of
the neuronal-type of splicing. We have shown that a strong 3'A is required for
splicing because exchanging it for a weaker one abolishes splicing. A second
region spanning the entire exon 25 downstream of the 3'A is also necessary for
the repression of the muscle-specific splicing in neuronal cells. In addition the
tissue-specific (muscle/neuron) selection of the appropriate 5' donor splice site
seems to be determined by at least two distinct but adjacent negative cis-active
elements located in the last 237 nt of the optional exon 24. The upstream
negative element controls the neuronal splicing while the downstream one
represses the muscle-specific splicing in neuronal cells. It is suggested that
the cis-active elements in the gene transcript are the target of trans-acting
factors that are responsible for the repression of neuronal- or muscle-specific
splicing in a tissue-specific manner.
PMID- 9645965
TI - AP-1, CREB and CBP transcription factors differentially regulate the tyrosine
hydroxylase gene.
AB - The tyrosine hydroxylase (TH) gene encodes the rate-limiting enzyme in the
biosynthesis of catecholamines. We have investigated the roles of two elements of
the TH promoter, the TH-'Fat Specific Element' (TH-FSE) which binds the Fos-Jun
complex, and the cAMP Response Element (CRE), which binds CREB and the co
activator protein, CREB Binding Protein (CBP) in regulating TH gene
transcription. In PC12 cells, the TH-FSE was required for induction by NGF while
the CRE was required for induction by cAMP. We show that both elements can
function independently and contribute strongly to TH promoter basal activity in
PC12 cells. We employed transient expression in the F9 teratocarcinoma cell line
to vary experimentally the levels of the nuclear regulators implicated in TH
control by the PC12 studies. In F9 cells, the TH promoter was strongly activated
by Fos and Jun, and by PKA-stimulated CREB protein. In F9 and NIH3T3 cells, CBP,
a co-activator which targets Fos-Jun and PKA-stimulated CREB, also induced the TH
promoter. Immunohistochemical studies in rat brain regions enriched in
dopaminergic neurons, including the midbrain and olfactory bulb (OB), suggest
that Fos-Jun and CREB make differential contributions to TH gene activity in
different tissues. Whereas changes in Fos protein levels parallel decreases in TH
protein upon olfactory deprivation, CBP levels remain unchanged. This suggests
that CRE-associated factors, including CBP, are not major regulators in the OB.
In contrast, the presence of CREB and the absence of Fos immunoreactivity in
midbrain dopaminergic cells suggests that the CRE is the primary regulator in
this region.
PMID- 9645967
TI - Chronic administration of cannabinoids regulates proenkephalin mRNA levels in
selected regions of the rat brain.
AB - This study was designed to examine the interactions between the cannabinoid and
enkephalinergic systems in the rat brain. To this aim, we have examined the
effects of subchronic (5 days) administration (10 mg.kg-1.day-1; i.p.) of delta 9
-tetrahydrocannabinol (THC) or R-methanandamide (AM356) and chronic (18 days)
administration with the synthetic cannabinoid receptor agonist CP-55,940 (1 mg.kg
1.day-1; i.p) on proenkephalin (PENK) mRNA levels in several brain regions of the
rat. Twenty micrometer brain sections from striatum, nucleus accumbens,
paraventricular nucleus, ventromedial nucleus, periaqueductal grey matter and
mammillary nucleus were hybridized with an oligonucleotide probe complementary to
PENK using in situ hybridization technique. Subchronic administration of THC or
AM356 increased PENK mRNA levels in the ventromedial nucleus of the hypothalamus,
(82%) and (39%), in the periaqueductal grey matter, (97%) and (49%), and
mammillary nucleus, (43%) and (9%), respectively. In contrast, both drugs were
without effect in the striatum and nucleus accumbens. On the other hand, chronic
administration of CP-55,940 increased PENK mRNA levels in the striatum (44%),
nucleus accumbens (25%), paraventricular (31%) and ventromedial nuclei of the
hypothalamus (41%). These results revealed that chronic cannabinoid
administration increases opioid gene expression in the rat central nervous system
and suggest an interaction between the cannabinoid and enkephalinergic systems
that may be part of a molecular integrative response to behavioral and
neurochemical alterations that occur in cannabinoid drug abuse.
PMID- 9645966
TI - Differential regulation of AP-1 DNA binding activity in rat hypothalamus and
pituitary by estrogen.
AB - Ap-1 proteins such as Fos and Jun are nuclear transcription factors that have
been postulated to function as third messengers in signal transduction pathways
to regulate target gene expression. Using electrophoretic mobility shift assays
(EMSA), we have studied estrogen (E) effects on regulation of AP-1 DNA binding
activity in the rat hypothalamus and pituitary. AP-1 binding is defined herein as
the specific association with a consensus AP-1 site during EMSA. Specific AP-1
binding activity was observed in nuclear extracts from the hypothalamus and
pituitary of ovariectomized (OVX) female and castrated (CAS) male rats. Treatment
with E increased the levels of AP-1 binding activity in the pituitary and uterus,
whereas E decreased the levels of AP-1 binding in the hypothalamus, of OVX
females. These effects were observed within 60 min and maintained for at least 72
h after a single dose of estrogen. Estrogen-induced changes in AP-1 binding were
much more prominent in OVX females than in CAS males. Treatment with progesterone
in OVX females had no significant effects on AP-1 binding activity in either
pituitary or hypothalamus. Analysis of AP-1 binding activity in both hypothalamus
and pituitary by supershift, immunodepletion and shift-Western blot indicated
that part of the AP-1 binding was due to the presence of Fos and Jun proteins.
However, Western blot analysis shows that the levels of Fos and Jun proteins in
the hypothalamic nuclear extracts were not altered by E treatment. We conclude
that E produced tissue and sex-differentiated alterations in AP-1 DNA binding
activity in the hypothalamus and pituitary of female rats, which may be related
to differential estrogenic actions on gene regulation.
PMID- 9645968
TI - Reduction of cortical infarction and impairment of apoptosis in NGF-transgenic
mice subjected to permanent focal ischemia.
AB - The neuroprotective potential of the nerve growth factor (NGF) against permanent
ischemic brain damage has been investigated in vivo using NGF-transgenic (tg)
mice. The expression of the transgene is driven by part of the promoter of the
proto-oncogene c-fos, which belongs to the first set of genes activated after
brain ischemic insult. Wild-type (wt) mice and tg mice were subjected to
permanent focal ischemia induced by electrocoagulation of the middle cerebral
artery. Twenty four hours (h) after the ischemic shock, when compared to wt, tg
mice displayed a 40% reduction of the infarcted area, which lasted up to 1 week.
However, infarcted brain areas were similar in wt and tg mice within the first
hours post-occlusion, indicating that NGF acted to block the progression of
neuronal damage. Kinetics of NGF synthesis assessed by ELISA was in good
agreement with the observed neuroprotective effect, since NGF content peaked 6 h
post-ischemia. This was further correlated with the time-course of c-Fos
immunoreactivity, detectable only from 6 h post-ischemia. The neuroprotective
effect of NGF involved the impairment of apoptotic cell death, as evidenced by a
marked decrease of the number of apoptotic profiles inside the ischemic zone in
tg mice. These results underline the potential of c-fos-NGF-tg mice to study in
vivo the molecular and cellular mechanisms of the NGF-induced neuroprotective
effect against ischemic damage.
PMID- 9645969
TI - Regulation of kappa-opioid receptor mRNA level by cyclic AMP and growth factors
in cultured rat glial cells.
AB - The mRNA of the kappa-opioid receptor (KOR) has been found recently in cultured
astrocytes and in microglia. By using RT-PCR and Southern hybridization, we
confirmed these observations and, in addition, we observed that KOR mRNA was
expressed in oligodendrocytes and in the precursors of astrocytes and
oligodendrocytes. KOR mRNA level was the highest in the immature astrocytes and
decreased with their maturation. Very few data are available on the regulation of
KOR level by extracellular signals. Therefore, we examined the effect of three
growth factors known to be present in the adult brain, basic fibroblast growth
factor (bFGF), platelet-derived growth factor (PDGF-BB) and leukemia inhibitory
factor (LIF) and of two cyclic AMP (cAMP) generating systems, the cAMP analog, 8
(4-chlorophenylthio)-cAMP and forskolin, on this level. It was found that in
astrocytes, KOR mRNA level decreased dramatically under the effect of cAMP and
less under the effect of bFGF while it did not change significantly after LIF
treatment. In oligodendrocytes, it also decreased with cAMP, but increased under
the effect of bFGF and PDGF-BB. In microglia, a decrease was observed with cAMP
and lipopolysaccharides (LPS), the most used activators of macrophages. These
results shed new evidence on the expression of opioid receptor mRNA in the glial
cells of the rat CNS. The regulation of KOR mRNA level under the effect of
extracellular signals suggests that opioids take part in dynamic processes in
glial cells, possibly related to glial-neuron communication.
PMID- 9645970
TI - Antisense oligonucleotides to the GluR2 AMPA receptor subunit modify excitatory
synaptic transmission in vivo.
AB - In the brain, fast wxcitatory synaptic transmission is mostly mediated by the
alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) subtype of the
glutamate receptors. Molecular cloning has revealed that four subunits, GluR1,
GluR2, GluR3, and GluR4 form heteromeric receptors with high affinity for AMPA.
Because antagonists and agonists do not discriminate between individual AMPA
receptor subunits, we decided to use antisense oligonucleotides to block the
expression of the GluR2 subunit within the receptor complex in adult animals. In
the present study, we exploited several advantages afforded by the guinea pig
cochlea to determine whether an antisense oligonucleotide directed to the mRNA of
the GluR2 subunit could modify primary auditory neurotransmission. While a random
probe with the same base composition had no effect, a GluR2 antisense
oligonucleotide, continuously delivered into the cochlea, transiently reduced the
compound action potential and diminished spontaneous activity of single auditory
nerve fibers. Although antisense oligonucleotides penetrated a variety of cells,
their effect could be physiologically localized to a single site of GluR2
antisense probe action, the primary auditory neuron. Subunit specificity of this
effect was confirmed by a significant reduction in GluR2/3, but not GluR4
immunoreactivity in primary auditory neurons. Besides being the first
demonstration that transient knockout of GluR2 subunit in adult animal modifies
excitatory synaptic transmission in vivo, these results support the use of the
antisense strategy as a powerful tool for blocking expression of any gene in the
cochlea.
PMID- 9645971
TI - RT-PCR analysis of mRNA expression of natriuretic peptide family and their
receptors in rat inner ear.
AB - To assess the possible physiological role of the atrial natriuretic peptide (ANP)
family, we investigated the expression of mRNA of ANP, brain natriuretic peptide
(BNP), C-type natriuretic peptide (CNP), and their receptors in rat inner ear
using the reverse transcription-polymerase chain reaction method. ANP and CNP
message bands were detected in the inner ear, but the BNP message band was not.
Amplification products of the expected sizes of ANP-A, ANP-B and ANP-C receptors
were detected in the inner ear. These results suggest that natriuretic peptide
family may influence the function of the inner ear through the ANP-A, ANP-B, and
ANP-C receptors.
PMID- 9645972
TI - Acute 17 beta-estradiol treatment down-regulates serotonin 5HT1A receptor mRNA
expression in the limbic system of female rats.
AB - In situ hybridization histochemistry was used to investigate acute estrogen
effects on serotonin 5HT1A receptor mRNA levels in limbic-related brain areas in
the female ovariectomized rat. Acute administration of 17 beta-estradiol (10
micrograms) decreased 5HT1A receptor mRNA expression levels within the medial
amygdala (after 2 and 24 h), piriform cortex (after 2 and 24 h), and perirhinal
cortex (after 24 h). No changes in 5HT1A mRNA levels were observed in hippocampus
or retrosplenial cortex. The findings suggest specific regional effects of
estrogen on 5HT functions mediated through regulation of the 5HT1A gene.
PMID- 9645973
TI - Isolation and characterization of a leech neuropeptide in rat brains: coupling to
nitric oxide release in leech, rat and human tissues.
AB - The osmoregulator peptide (leech osmoregulatory factor, LORF; IPEPYVWD) was first
found in the leech central nervous system (CNS). Given the fact that certain
peptides can be found in mammals and invertebrates, e.g., opioid, we examined rat
brains to determine if LORF was present. This peptide was found and isolated by
successive reversed-phase HPLC purification steps and characterized by
electrospray mass spectrometry measurement. It was sequenced by Edman degradation
and quantified in different tissues by ELISA. Our results demonstrate the
presence of LORF in the hypothalamus, thalamus, and striatum (6 pmol/mg of
protein extract) and in other brain areas at lower levels. This octapeptide is
also present in the rat duodenum and liver (10 to 14 pmol/mg) and at lower levels
in heart, lung, pancreas and caudal spinal cord (< 5 pmol/mg). The testes,
adrenals and kidneys have the lowest levels of all the tissues examined (ca. 0.5
pmol/mg of protein). Furthermore, we also demonstrate that LORF is coupled to
nitric oxide (NO) release in leech CNS, rat hypothalamus and human saphenous vein
in a manner which is inhibited by a nitric oxide synthase inhibitor as well as an
antibody directed toward LORF. The study demonstrates that LORF, and its function
in relation to NO release, has been conserved over more than 400 million years of
evolution.
PMID- 9645974
TI - Cerebral cysticercotic arteritis: detection and follow-up by transcranial
Doppler.
AB - Intracranial arteritis is a well-known complication of cerebral cysticercosis.
The aim of this study was to explore the possible role of transcranial Doppler
(TCD) in the evaluation of cysticercotic arteritis in 9 patients with
subarachnoid cysticercosis and stroke. Arteritis of main basal vessels was
detected by TCD in 7 of 10 arterial lesions that were demonstrated by cerebral
angiography. The Doppler pattern was occlusive in 2 cases and stenotic in 5. In
the 3 patients with lacunar infarcts, both cerebral angiography and TCD were
normal. In 6 arterial lesions followed serially with TCD a stenotic pattern
resolved within 4 and 6 months in 3 cases and remained in the stenotic range at
12 months in 1 case, whereas an occlusive pattern persisted at 6 and 18 months in
the other 2 cases. In conclusion, TCD may be useful to detect and follow up
cerebral vasculitis due to chronic cysticercotic arachnoiditis.
PMID- 9645975
TI - Predictive clinical factors of in-hospital mortality in 231 consecutive patients
with cardioembolic cerebral infarction.
AB - Cardioembolic cerebral infarction is a subtype of stroke with a high mortality.
The purpose of this study was to determine predictors of in-hospital mortality in
231 consecutive patients with cardioembolic stroke by means of a multivariate
analysis. Three predictive models were constructed. A first model was based on
demographic, anamnestic and clinical variables collected at the bedside
examination (total 8 variables). A second model was based on clinical and
neuroimaging variables (total 10 variables). A third model was based on the
aforementioned clinical and neuroimaging variables and the presence of early
recurrent embolism (total 11 variables). Deteriorated level of consciousness,
limb weakness, presence of congestive heart failure, male gender, and age
appeared to be independent prognostic factors of in-hospital mortality in the
predictive model based on clinical variables and in the predictive model based on
clinical and neuroimaging variables. In addition to these variables, early
recurrent embolization was selected in the third predictive model. In the first
two models, setting a cut-off point of 0.50 for predicting vital status at
hospital discharge resulted in a sensitivity of 60%, a specificity of 89% and a
total correct classification of 81%. The corresponding values of the third model
were 62, 89 and 81%, respectively. These data may help clinicians to establish an
early prognosis of this stroke subtype more accurately as well as to allocate
patients with cardioembolic stroke in clinical trials correctly.
PMID- 9645976
TI - Different vascular risk factor profiles among cortical infarcts, small deep
infarcts, and primary intracerebral haemorrhage point to different types of
underlying vasculopathy. A study from the L'Aquila Stroke Registry.
AB - The type of small-vessel disease in small deep (lacunar) infarcts (SDIs) remains
contentious as opposed to that in primary intracerebral haemorrhage (PICH), which
is lipohyalinosis in most cases. Therefore, we compared risk factor profiles as
indicators of underlying vessel pathology, between patients with SDI and patients
with PICH, and those with a non-cardio-embolic infarct involving the cortex
(CORTI). Multivariate regression analysis showed the diabetes mellitus [odds
ratio (OR) 0.56; 95% confidence interval (CI) 0.34-0.90] and
hypercholesterolaemia (OR 0.63; 95% CI 0.40-0.99) were more strongly associated
with CORTI than with SDI. Carotid stenosis was associated with SDI in comparison
with PICH (OR 7.5; 95% CI 1.02-54.94). Compared with PICH, CORTI was more
strongly associated with diabetes mellitus (OR 3.27; 95% CI 1.38-7.76), carotid
stenosis (OR 24.42; 95% CI 4.99-119.45), and hypercholesterolaemia (OR 3.12; 95%
CI 1.47-6.65), whereas hypertension was associated with PICH (OR 0.37; 95% CI
0.18-0.79). These data support the hypothesis that small-vessel atheromatosis
rather than small-vessel lipohyalinosis underlies lacunar infarcts in most cases.
PMID- 9645977
TI - Carotid endarterectomy does not affect long-term blood pressure: observations
from the NASCET. North American Symptomatic Carotid Endarterectomy Trial.
AB - The aim of the study was to examine how blood pressure is affected by carotid
endarterectomy over a 2-year period. We analyzed the data from 997 patients who
received best medical care alone and 999 patients who received best medical care
plus carotid endarterectomy (CE). All patients were recruited by the North
American Symptomatic Carotid Endarterectomy Trial and were followed at regular
clinic visits. The mean blood pressure at baseline was 145.2/81.2 mm Hg for
medically treated patients and 146.2/81.9 mm Hg for surgically treated patients.
The mean systolic and diastolic pressures increased by approximately 2.5% in the
first month following randomization, then decreased over the next year and then
remained relatively uniform. Throughout follow-up, surgical patients had slightly
higher blood pressures than medically treated patients. At the end of 2 years,
the mean systolic pressures in the two treatment groups converged to 147.6 mm Hg.
The mean diastolic pressure in the medical patients returned to its baseline
value, whereas the surgical patients' blood pressure remained slightly elevated
by 0.5 mm Hg. The percentage of patients on antihypertensive medications mirrored
the rise and fall in blood pressures. A sharp decrease in medication (from 56 to
43%) was observed in both treatment groups at 1 month. The percentage of patients
on medication increased subsequently, with approximately 63% taking medication at
the end of 2 years. CE does not affect long-term blood pressure. The use of
antihypertensive medications appears to be the key component in blood pressure
management. As hypertension is related to neurologic morbidity and mortality,
strict regulation of blood pressure is extremely important in patients with
cerebrovascular disease.
PMID- 9645978
TI - Cerebral venous thrombosis complicated by hemorrhagic infarction: factors
affecting the initiation and safety of anticoagulation.
AB - BACKGROUND AND PURPOSE: Anticoagulation (AC) may improve outcome in cerebral
venous thrombosis (CVT), even when complicated by pretreatment hemorrhagic
infarction (HI). The HI characteristics which affect the decision to initiate AC
therapy and its outcome are unknown. We reviewed our experience with AC treatment
for patients with CVT and HI. METHODS: Retrospective study. RESULTS: Two groups
of patients were compared: those who received AC (n = 6) and those who did not (n
= 6). Hemorrhage volumes ranged from petechial to large (93 cm3) hematoma with
mass effect. Anticoagulated patients received treatment a mean of 11.3 days after
symptom onset. Each had exclusively extratemporal HI without midline shift and
had stable hemorrhage volumes and clinical status for at least 24 h prior to AC.
AC did not increase HI volume or worsen clinical outcome. All 6 non-AC patients
had enlarging hematomas. Four of these 6 patients had temporal HI; and two
required hematoma resection. CONCLUSIONS: AC therapy was avoided in CVT patients
with HI that were located in the temporal lobe, caused midline shift or were
enlarging. AC was safely initiated within several days in clinically stable
patients with non-temporal-lobe HI of unchanging volume. We suggest that the
location and unchanged volume on serial CT may be important factors influencing
the safety of AC therapy in patients with CVT and HI.
PMID- 9645980
TI - Clinical and ultrasonic long-term results of percutaneous transluminal carotid
angioplasty. A prospective follow-up of 30 carotid angioplasties.
AB - Experience of the long-term outcome of patients treated with carotid balloon
angioplasty is limited. Therefore, we prospectively analyzed the ultrasonic and
clinical features of 29 patients with complete follow-up data beyond 24 months,
evaluated from 1989 through 1996 from our carotid angioplasty cohort of 106
patients. Mean follow-up time was 33 months. For up to 78 months postangioplasty,
23 patients with 24 angioplasties (77%) had no further neurological sequelae.
Single ipsilateral amaurosis fugax or TIA events occurred in 3 patients.
Recurrent ipsilateral amaurosis fugax or TIA events were noted twice in 2
patients. No patient suffered an ipsilateral stroke. Fifteen angioplasties (50%)
remained with normal ultrasound (stenosis < 50%), mild restenosis (50-70%)
occurred in 12 angioplasties (40%), and severe restenosis (> 70%) in 3
angioplasties (10%). Only in 2 of 15 patients clinical complications were related
to the occurrence of ipsilateral restenosis above 50%. Until now, rigorous and
careful evaluation of patients and clinical and ultrasonic follow-up have been
essential for the estimation of the long-term efficacy of carotid angioplasty. It
should be noted that carotid angioplasty is a new technique in evolution, with a
high potential improving the technical results.
PMID- 9645979
TI - Safety and tolerability of 619C89 after acute stroke.
AB - BACKGROUND: 619C89 is a use-dependent sodium channel blocker which reduces
hemispheric infarction volume by up to 60% after permanent middle cerebral artery
occlusion in rats. Intravenous doses of up to 1 mg/kg have been well tolerated by
healthy young and elderly volunteers. This study sought to assess safety and
tolerability of 619C89 in the treatment of acute stroke. METHODS: Patients were
randomised within 12 h of onset of stroke to receive 619C89 or placebo as an
intravenous loading dose, followed by maintenance doses given 8 hourly for 64 h
in a double-blind, ascending-dose tolerance study. Dosing commenced at 0.5 mg/kg
loading plus 0.25 mg/kg/8 h maintenance for the first group and increased in
increments of 0.5 mg/kg loading +0.25 mg/kg/8 h maintenance thereafter. Safety
evaluation was continued for 3 months. RESULTS: 48 patients were recruited. 12
received placebo and 36 received 619C89 in doses up to 2.5 mg/kg loading plus
1.25 mg/kg/8 h. Dose escalation was stopped after the occurrence of
hallucinations in 5 of 18 patients who received 2 mg/kg/8 h or more. Gastro
intestinal upset and confusion were also possibly drug related. No drug-related
effects on cardiovascular function were found. CONCLUSIONS: 619C89 was associated
with significant central nervous system side-effects at doses of 2 mg/kg + 1
mg/kg/8 h or greater as discrete intravenous infusions within 12 h of stroke
onset. It may also cause gastro-intestinal side-effects. Doses below this are
well tolerated in patients. No adverse cardiovascular effects were seen.
PMID- 9645981
TI - Alpha-1-antitrypsin deficiency in spontaneous intracranial arterial dissections.
AB - alpha 1-Antitrypsin deficiency has been associated with a variety of vascular
disorders including arterial aneurysms, spontaneous extracranial arterial
dissections, and arterial fibromuscular dysplasia. We determined the distribution
of alpha 1-antitrypsin phenotypes in patients with intracranial arterial
dissections, a rare cause of subarachnoid hemorrhage. The study population
consisted of 4 consecutive patients with subarachnoid hemorrhage due to
spontaneous intracranial arterial dissections. The vertebral artery was involved
in 3 patients and the posterior inferior cerebellar artery in 1 patient. Three of
these 4 patients were found to have a heterozygous alpha 1-antitrypsin deficiency
(PiMZ or PiMS phenotypes). These data support previous studies suggesting that
patients with alpha 1-antitrypsin deficiency may be at an increased risk of
developing spontaneous arterial dissections.
PMID- 9645982
TI - Thrombo-embolic stroke, moya-moya phenomenon and primary oxalosis.
AB - We present the clinical, radiological and autopsy findings in a 32-year-old woman
with primary oxalosis, who suffered recurrent bilateral carotid territory
infarcts. The overall features were those of moya-moya syndrome, with bilateral,
ultimately thrombotic, occlusion of the distal internal carotid arteries. Vessel
pathology suggests an underlying intimal vasculopathy, the possible relation of
which to the patient's metabolic abnormality is discussed.
PMID- 9645983
TI - Cheiroretroauricular syndrome: a restricted form of pure sensory stroke due to a
pontine hematoma.
PMID- 9645984
TI - Severe preeclampsia/eclampsia: hypertensive encephalopathy of pregnancy?
PMID- 9645985
TI - Neuroprotection as initial therapy in acute stroke. Third Report of an Ad Hoc
Consensus Group Meeting. The European Ad Hoc Consensus Group.
AB - Although a considerable body of scientific data is now available on
neuroprotection in acute ischaemic stroke, this field is not yet established in
clinical practice. At its third meeting, the European Ad Hoc Consensus Group
considered the potential for neuroprotection in acute stroke and the practical
problems attendant on the existence of a very limited therapeutic window before
irreversible brain damage occurs, and came to the following conclusions.
NEUROPROTECTANTS IN CLINICAL DEVELOPMENT: Convincing clinical evidence for an
efficacious neuroprotective treatment in acute stroke is still required. Caution
should be exercised in interpreting and extrapolating experimental results to
stroke patients, who are a very heterogeneous group. The limitations of the time
windows and the outcome measures chosen in trials of acute stroke therapy have an
important influence on the results. The overall distribution of functional
outcomes provides more statistical information than the proportion above a
threshold outcome value. Neurological outcome should also be assessed.
Neuroprotectants should not be tested clinically in phase II or phase III trials
in a time window that exceeds those determined in experimental studies. The
harmful effects of a drug in humans may override its neuroprotective potential
determined in animals. Agents that act at several different levels in the
ischaemic cascade may be more effective than those with a single mechanism of
action. CURRENT IN-HOSPITAL MANAGEMENT OF ACUTE STROKE: The four major
physiological variables that must be monitored and managed are blood pressure,
arterial blood gas levels, body temperature, and glycaemia. The effects of
controlling these physiological variables have not been studied in prospective
trials, though they may all contribute to the outcome of acute ischaemic stroke
and affect the duration of the therapeutic window. Optimal physiological
parameters are inherently neuroprotective. Trials of new agents for the treatment
of acute stroke should aim to maintain these physiological variables as close to
normal as possible, and certainly within strictly defined limits. THE PLACE OF
NEUROPROTECTANTS IN ACUTE STROKE MANAGEMENT: Stroke patients are a very
heterogeneous group with respect to stroke mechanisms and severity, general
condition, age and co-morbidities. At the present time, the only firm guideline
than can be proposed for patient selection is the need for early admission to
enable neuroprotectant and/or thrombolytic treatment to be started as soon as
possible within the therapeutic window. The severity of potential side-effects
will largely determine who should assess a patient with suspected stroke and
initiate treatment. There is little information on which to base the duration of
neuroprotectant therapy, and more experimental data are needed. Even if
prehospital treatment proves to be feasible, it should not replace comprehensive
stroke management in a specialist hospital unit. Clinical trials of
neuroprotectants should only be performed in stroke units. The combined approach
of restoring blood flow and providing neuroprotection may be the most productive
in human stroke, but current clinical trial design will have to change in order
to test combination therapy. Important side-effects are those that interfere with
any possible benefit or increase mortality. PHARMACO-ECONOMIC ASPECTS OF
NEUROPROTECTANTS: The early increase in hospital cost associated with
neuroprotectant therapy may be balanced by the shorter length of hospital stay
and lesser degree of disability of the surviving patients. The overall direct
financial cost is highly dependent on the number of patients eligible for
neuroprotectant therapy, which is itself dependent on the length of the
therapeutic window and the severity of potential side-effects. A treatment that
achieves a good functional outcome is the most cost-effective approach.
PMID- 9645986
TI - Type 1 diabetes and enterovirus infections. Proceedings of a meeting. Helsinki,
Finland.
PMID- 9645987
TI - Accomplishments and challenges in picornavirology as observed by a medical
doctor.
AB - BACKGROUND: The family of picornaviridae has been studied extensively: the
structure of the virion and its replication strategy are known in molecular
detail. Nevertheless, infections with the multitude of enteroviruses still cause
widespread epidemics, serious disease and a diversity of clinical syndromes
ranging from central nervous system involvement to light febrile illness.
Infections with more than 100 human rhinovirus types are an important economic
factor. OBJECTIVE: In order to treat and control picornavirus infections with
their great diversity of manifestations the pathogenesis of diseases must be
better understood, e.g. concerning virus spread in the organism or molecular
detail of the disease processes, such as cell tropism of the virus or cytokine
and immunologic actions. Elucidation of mechanisms of virus transmission in the
population is also needed. STUDY DESIGN: This review discusses aspects of our
present knowledge of the pathogenesis, transmission, prophylaxis and treatment of
picornavirus infections. CONCLUSIONS: The need for further development of
selective antiviral substances, safe vaccines and basic research in
picornavirology is stressed.
PMID- 9645988
TI - Enterovirus infections and insulin dependent diabetes mellitus--evidence for
causality.
AB - BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) has a long subclinical
period characterised by gradually progressing autoimmune damage of insulin
producing beta-cells. Clinical IDDM is manifested when 90% of beta-cells have
been destroyed. Several studies have indicated that enterovirus infections,
coxsackievirus B (CVB) infections especially, are frequent at the manifestation
of clinical IDDM suggesting that they can precipitate the symptoms of IDDM in
individuals who already have an advanced beta-cell damage. Recently, the first
prospective studies have been published suggesting that enterovirus infections
can also initiate the process several years before clinical IDDM. This implies
that enterovirus infections may have a crucial role in the pathogenesis of human
IDDM. OBJECTIVE: The recent findings have brought up the question whether the
time has come when a causal association between enterovirus infections and IDDM
could finally be confirmed. This review focuses on this question summarising the
current knowledge and the prospects of future research. STUDY DESIGN: Review of
the recent progress in studies evaluating the role of enterovirus infections in
human IDDM. CONCLUSIONS: The currently available information supports the
assumption that the role of enterovirus infections may be more important than
previously estimated. Enterovirus infections are obviously associated with
increased risk of IDDM, but whether this association reflects causal relationship
remains to be confirmed in future studies. Prospective birth-cohort studies will
be among the most important ones giving important data on the etiologic fraction
of enterovirus infections, the properties of diabetogenic virus variants and the
mechanisms of beta-cell damage.
PMID- 9645989
TI - The pathogenesis of viral-induced diabetes.
AB - Serologic case-control studies have suggested an association between coxsasckie
group B viruses and insulin-dependent diabetes mellitus (IDDM). New
investigations have identified enteroviral nucleic acid in the peripheral blood
mononuclear cells of newly-diagnosed patients with IDDM. The disease pathogenesis
is dependent on several factors. including the genetics of the host, strain of
virus, activation status of autoreactive T-cells, upregulation of pancreatic MHC
1 antigens, molecular mimicry between viral and beta cell epitopes and direct
islet cell destruction by viral cytolysis. Epitopes (IDDM-E1 and E2) on glutamate
decarboxylase 65 (GAD65) are the most common targets for antibody and cellular
mediated autoimmune beta cell destruction.
PMID- 9645990
TI - Molecular epidemiology of enteroviruses with special reference to their potential
role in the etiology of insulin-dependent diabetes mellitus (IDDM). A review.
AB - BACKGROUND: Several lines of evidence suggest that enterovirus infections may be
involved in the etiology of the insulin-dependent diabetes mellitus (IDDM). Often
in the literature, a reference is given to specifically diabetogenic strains of
enterovirus but there is no systematic assessment about the generation of such
strains in the course of evolution or about their abundance among the 64
enterovirus serotypes pathogenic to man. If enteroviruses truly are involved in
the etiology of IDDM, a possibility to prevent the disease with enterovirus
vaccines might become feasible. In such a situation it would be important to know
which serotypes and strains are the most important ones, and whether there would
be differences between the strains as regards the pathogenetic mechanisms
involved. OBJECTIVE: To present a brief summary of the basic biology of
enteroviruses, on existing data of genetic variation of enteroviruses, and on
molecular epidemiology of human enteroviruses with special reference to the
different epidemiological modes of their putative involvement in the pathogenesis
of IDDM. CONCLUSIONS: Like RNA viruses in general, enteroviruses exist as a
quasispecies, a mixture of genetic microvariants with a vast potential to adapt
to new environments. This means that specifically beta cell-tropic and
potentially diabetogenic variants could, in theory, emerge sporadically during
systemic infection of any individual. The patterns of genetic diversification of
enteroviruses, cocirculation of separate genetic lineages in the human
populations, and the assumed geographical restrictions of endemic transmission of
the lineages, allow one to hypothesize that populations with a high persisting
IDDM incidence might be endemically infected by some specific strains of
enteroviruses. However, so far, there is no systematically collected data
supporting this hypothesis.
PMID- 9645991
TI - Nucleotide sequence of an attenuated mutant of coxsackievirus B3 compared with
the cardiovirulent wildtype: assessment of candidate mutations by analysis of a
revertant to cardiovirulence.
AB - BACKGROUND: Coxsackievirus B3 (CVB3) causes myocarditis in the SWR (H2q) mouse
model and persistence of CVB3 in myocardium disposes to the development of
dilated cardiomyopathy. An attenuated strain of CVB3 has been isolated, sequenced
and several candidate mutations for attenuation identified. Derivation of a
revertant to cardiovirulence allows the significance of these mutations to be
assessed. OBJECTIVES: To ascertain which candidate mutation(s) determine(s) the
attenuated phenotype. STUDY DESIGN: A revertant to cardiovirulence was isolated
following passage through severe combined immunodeficient disease (SCID) mouse
heart. The 5'-non-translated region (NTR) and region coding for capsid proteins
were sequenced and compared to the wildtype and attenuant. RESULTS: There are
five candidates for attenuation: (1) A-G at base 580 in the 5'-NTR; (2) A-T at
base 690 in the 5'-NTR; (3) CG-GC at bases 1401/2 (Thr to Ser at amino acid 151
in VP2); (4) AA-GT at bases 2691/2 (Lys to Ser at amino acid 80 in VP1); (5) A-G
at base 2916 (Asp to Gly at amino acid 155 in VP1). It was shown previously that
mutations at 580, 690 and 2691/2 are not important in attenuation. Additionally,
there are three novel mutations in the coding region of the revertant and one in
the 5'-NTR which are unlikely to be relevant for attenuation as they are not
present in the attenuant. Of nucleotide changes seen at 1401/2 and 2916 in the
attenuant, only 2916 reverts to the wildtype sequence and so is a strong
candidate for a determinant of attenuation.
PMID- 9645992
TI - An approach to understanding the mechanisms of poliovirus persistence in infected
cells of neural or non-neural origin.
AB - BACKGROUND: Poliovirus (PV) is the etiologic agent of paralytic poliomyelitis,
which is sometimes followed, after decades of clinical stability, by new
symptoms, including progressive muscular atrophy, collectively known as the post
polio syndrome. This raises the question of possible PV persistence in post polio
patients. OBJECTIVE: To test the capacity of PV to establish persistent
infections in human cells, three models were developed. STUDY DESIGN: This review
focuses on the viral and cellular parameters involved in persistent PV infection.
RESULTS: Many PV strains, which are generally lytic in primate cell lines, are
able to establish persistent infections in human neuroblastoma cells. During
persistent infection, PV mutants (PVpi) are consistently selected, and several of
their capsid substitutions occur at positions known to be involved in PV-PV
receptor interactions. PVpi have a particular property: they can establish
persistent infections in non-neural HEp-2 cells. PV can also persistently infect
primary cultures of human fetal brain cells and the majority of cells which
survive infection belong to the neuronal lineage. CONCLUSIONS: The results
obtained with the three models of persistent PV infection in human cells suggest
that several mechanisms are used by PV to establish and maintain persistent
infections in neural and non-neural cells. The interactions of the virus with its
receptor seem to be a key-step in all cases. In the future, the elucidation of
the etiology of the post-polio syndrome will require the characterization of PV
sequences having persisted for decades in post-polio patients.
PMID- 9645993
TI - Coxsackie B virus and its interaction with permissive host cells.
AB - BACKGROUND: Observations in humans and the results of experiments on laboratory
animals have provided evidence that coxsackieviruses of group B (CVB) are major
etiologic agents of acute and chronic enterovirus myocarditis and various other
virus-induced diseases. OBJECTIVE: This minireview briefly summarizes the
investigations to elucidate various molecular mechanisms for the induction and
maintenance of persistent CVB infections. With regard to the recent findings that
CVB may use several different receptor proteins, this article focuses on virus
host cell interactions and the potential impact of these interactions for
enteroviral replication. STUDY DESIGN: The interaction of CVB with specific cell
surface proteins was analyzed in cultured cell lines and murine tissues at the
level of virus attachment and virus internalization. As example for the
interaction of CVB with intracellular proteins, the state of p21rasGTPase
activating protein (RasGAP) was investigated in mock-infected and CVB3-infected
HeLa cells. RESULTS AND CONCLUSIONS: The experiments to elucidate the virus
receptor interactions revealed the necessity to differentiate between CVB
attachment proteins and proteins involved in virus internalization. Since more
than one protein may be required to initiate the uptake of CVB into permissive
host cells, a model of the putative interaction of these proteins within a
multimeric receptor complex is proposed. It is further tempting to speculate that
the presence of multiple attachment proteins may influence the tissue tropism of
CVB as well as pathogenicity.
PMID- 9645994
TI - Coxsackie B virus infection and beta cell autoantibodies in newly diagnosed IDDM
adult patients.
AB - BACKGROUND: Environmental agents such as viruses have been identified as
potentially important determinants of insulin-dependent diabetes mellitus (IDDM).
Enterovirus infections, Coxsackievirus B especially, could be linked to the beta
cell damaging process and to the onset of clinical IDDM. OBJECTIVES: Enteroviral
(EV) infection and beta cell autoimmunity were studied in adult patients at the
onset of IDDM. STUDY DESIGN: A total of 14 newly diagnosed-IDDM patients with
ketosis or ketoacidosis were compared to, anteriorly diagnosed IDDM patients with
metabolic decompensation, non-IDDM patients with metabolic decompensation and
healthy adults. EV infection was studied by genomic RNA detection in whole blood
using a RT-PCR assay. In order to assess the level of beta cell autoantibodies at
the time of the initial metabolic decompensation, serum specimens from IDDM
patients were tested for GAD65 antibodies and islet cell antibodies (ICAs).
RESULTS: Coxsackie B3 or B4 virus genome was detected and genotyped in five of 14
(35.7) newly diagnosed IDDM patients and in one of 12 (8%) patients in the course
of IDDM. By contrast, none of the 12 non-IDDM patients and none of the 15 healthy
adults was positive for enterovirus RNA detection in whole blood. Positive GAD65
antibodies and ICAs assays were not significantly correlated to a positive EV-RNA
detection. CONCLUSION: The present study demonstrates that Coxsackie B virus RNA
sequences can be detected in the peripheral blood from adult patients at the
onset or in the course of IDDM and suggests that a Coxsackie B virus infection
could initiate or accelerate beta cell autoimmune damaging process.
PMID- 9645995
TI - Development of an enterovirus specific PCR method for the quantification of
enterovirus genomes in blood of diabetes patients.
AB - BACKGROUND: Insulin-dependent diabetes mellitus or type 1 diabetes is a disease
with a diverse aetiology. Epidemiological studies examining newly diagnosed,
recent onset IDDM patients have suggested a role for viruses in the aetiology of
IDDM (Yoon, 1995, Diabetes/Metabolism Reviews 11, 83-107). Important candidates
are the enteroviruses, in particular coxsackieviruses B3 and B4. The latter can
cause diabetes in animals (Clements et al., 1995, Lancet 346, 221-223).
OBJECTIVES: We have developed a quantitative PCR method for the detection of
enterovirus genomes in biological samples. The quantitative PCR will be used to
screen for enteroviruses in blood of diabetes patients and their relatives by
testing a Blood Diabetes Register. STUDY DESIGN: A substantial amount of data has
been collected on enterovirus induced IDDM, our study is original in so far as it
will be: (1) a quantitative study, not only the presence of viral genome
sequences in blood will be determined, but also their concentrations (viral
load); and (2) a longitudinal study, samples are and will be collected as a
function of time. Positive PCR samples will be quantified using the standard
addition method. RESULTS: The test is specific for enteroviruses, since all
enteroviruses were detected with equal sensitivity. Viruses belonging to other
picornavirus genera scored negative (even up to 3 x 10(6) genome copies). An
equal detection limit of 10 genome copies was found for all enteroviruses.
CONCLUSIONS: The developed method will permit us to generate quantitative and
longitudinal data of enterovirus genomes in blood of diabetes patients and their
relatives, which might help in the elucidation of the relationship between
enteroviruses and IDDM.
PMID- 9645996
TI - Demonstration of persistent enterovirus in the pancreas of diabetic mice by in
situ polymerase chain reaction.
AB - BACKGROUND: Although Enterovirus (EV) do not persist in the tissue, which is
essential to maintain autoimmunity, they have been associated as the cause of
chronic autoimmunity in some cases of insulin dependent diabetes mellitus (IDDM).
Convincing reports, demonstrating persistent EV infections in the pancreases, are
rare. OBJECTIVES: To determine the role of EV in IDDM, a mouse model was tested
and i situ polymerase chain reaction (ISPCR) developed. The major problem of
ISPCR are the high amounts of non-specific staining. In the current study we
developed an ISPCR protocol which minimised non-specific staining and allowed the
accurate localisation of the viral RNA in the tissue. STUDY DESIGN: Five mice
were infected with coxsackievirus group B4, sacrificed 7 weeks later and the
pancreases were harvested. The EV nucleic acid were localised and detected in the
pancreases by ISPCR. RESULTS: In the current study non-specific staining of
ISPCR, due to DNA repair and diffuse artefacts, were minimised and the EV nucleic
acids were localised in the beta cells of the endocrine pancreases in all five
diabetogenic mice. CONCLUSION: This study demonstrates an association of viral
RNA with the development of diabetes in mice and the usefulness of ISPCR to
determine the role of EV in IDDM.
PMID- 9645997
TI - Diagnosis of cytomegalovirus infection in HIV-infected patients with respiratory
disease.
AB - BACKGROUND: The role of the cytomegalovirus (CMV) in the respiratory morbidity
and mortality of HIV-infected patients remains unclear. This is due in part to
difficulties in making an accurate and rapid diagnosis. There has been a limited
number of studies, often with few or no AIDS patients, on the use of DNA-DNA in
situ hybridization (ISH) and polymerase chain reaction to diagnose CMV
respiratory infection directly on bronchoalveolar fluid samples. OBJECTIVES: To
compare the centrifugation culture (CC), ISH, and nested-primer polymerase chain
reaction (npPCR) techniques (npPCR) techniques on bronchoalveolar fluid for the
diagnosis of respiratory CMV infection. STUDY DESIGN: Samples were obtained
prospectively from a group of 35 HIV-infected homosexual men evaluated for
pneumonia at a university hospital. Sensitivity, specificity, and predictive
values of the three techniques were measured and compared, using the conventional
roller tube cell culture (CRTC) as the gold standard. RESULTS: Sensitivity,
specificity, positive and negative predictive values were as follows: 86%, 86%,
90%, and 80% for the CC; 5%, 100%, 100%, and 41% for ISH; and 86%, 57%, 75%, and
73% for npPCR. Of the six false positive samples by npPCR, two were positive by
CC (none by ISH). If the latter were considered true positives, the specificity
and positive predictive values of npPCR would increase to 67% and 83%,
respectively. CONCLUSIONS: CC appeared to be the best of the three techniques
compared in this study for diagnosis of respiratory CMV infection in HIV-infected
patients. The sensitivity and predictive values of DNA-DNA ISH were very poor.
Results with npPCR were acceptable, and this technique may be considered in
situations when rapid diagnosis of CMV infection is necessary.
PMID- 9645998
TI - Cell-fusion assay for the detection of rubella virus in Vero cells.
AB - BACKGROUND AND OBJECTIVES: Rubella virus (RV) produces a subtle and slow
developing cytopathic effect in Vero cells that is difficult to recognize,
especially at low multiplicities of infection. In order to facilitate the
detection of RV in cell culture, we standardized a low-pH virus-mediated cell
fusion assay. STUDY DESIGN: The incubation periods, temperatures, pH and
multiplicity of infection were established. The specificity of the method was
tested by immunofluorescence assay and cell-fusion inhibition by specific sera.
RESULTS: Six days post infection, Vero cells were treated for 5 min with fusion
medium. After that, monolayers were incubated with medium at neutral pH for 16 h
and then stained. Gigantic cells with multiple nuclei were observed. CONCLUSIONS:
The method allowed the observation of unequivocal images that are easier to
recognize than the cytopathic effect caused by RV in the same cell line. At the
same time, the method is simple, accessible and shown to be specific to
demonstrate the replication of several strains and isolates of RV in Vero cells.
PMID- 9645999
TI - Acute lower respiratory infections due to respiratory syncytial virus and
adenovirus among hospitalized children from Argentina.
AB - BACKGROUND: Acute lower respiratory infection (ALRI) is one of the main causes of
morbidity and mortality in small children. OBJECTIVE: The aim of this study was
to determine the frequency, seasonality and association with clinical entities of
respiratory syncytial virus (RSV) and adenoviruses in children with ALRI. STUDY
DESIGN: During 2 consecutive years (1991-1992), 168 children under 2 years of age
hospitalized due to ALRI in a public pediatric hospital of Buenos Aires,
Argentina, were studied. RSV and adenoviruses were investigated on nasopharyngeal
aspirates (NPA) by indirect immunofluorescence (IIF). HEp-2 cells were used for
adenovirus isolation. RESULTS: RSV was detected in 36.3% and adenoviruses in
14.3% of the cases (P < 0.0001). All adenoviruses detected by IIF were also
isolated in culture. Out of 61 RSV cases, 57% corresponded to bronchiolitis and
43% to pneumonia. Ninety-two per cent of children with RSV were less than 1 year
old and 70% were less than 5 months. The highest number of RSV cases were
observed during winter, with a clear peak in July. Seventy-one per cent of
adenovirus cases were associated with pneumonia and only 24% with bronchiolitis
(P < 0.02), and predominated in children older than 5 months of age (P < 0.0001).
Adenoviruses were detected in almost all months of the year with a small peak at
the end of winter and beginning of spring. No significant differences in clinical
features at admission, breast feeding or malnutrition were observed among
children with RSV or adenovirus diagnosis versus those with no viral etiology.
The overall fatality rate was 2.4%. In all fatal cases adenovirus was detected in
NPA. Thus, fatality rate among patients with adenoviruses reached 16.7%.
CONCLUSIONS: Our findings show the importance of RSV and adenoviruses associated
with ALRI in hospitalized children under 2 years of age and the different
epidemiological patterns of the two viruses in Buenos Aires, Argentina.
PMID- 9646000
TI - The clinical utility of viral quantitation using molecular methods.
AB - BACKGROUND: The quantitation of viral nucleic acids in biological fluids has
become increasingly desirable over the past several years. To this end, a number
of quantitative molecular procedures have been developed. OBJECTIVES: The
objective was to review the current literature on the molecular techniques used
in the quantitation of viral nucleic acids and to assess the appropriateness of
these methods for clinical use. RESULTS: Assays involving both target and signal
amplification are now available for the accurate and precise quantitation of
viral burden in infected patients. These methods include quantitative polymerase
chain reaction (PCR), branched chain signal amplification (bDNA), nucleic acid
sequence-based amplification (NASBA) and the SHARP signal and hybrid capture
systems. Our understanding of the natural history and pathogenesis of viruses
such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV),
hepatitis C virus (HCV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) may
be greatly facilitated by accurate determinations of viral and infected cell
burden. Quantitation of viral load in infected individuals may also be useful to
assess disease progression, monitor the efficacy of therapy and to predict
treatment failure and the emergence of drug-resistant viruses. CONCLUSION:
Precise, accurate and reproducible quantitation of viral load is now feasible.
Molecular assays for viral quantitation should have a considerable impact on
medical research and clinical care.
PMID- 9646001
TI - Human papillomavirus detection in cervical intraepithelial neoplasia by the
second-generation hybrid capture microplate test, comparing two different
cervical specimen collection methods.
AB - BACKGROUND: The second generation Hybrid Capture microplate-based human
papillomavirus (HPV) test (HC II) was examined to determine its sensitivity for
identification of cervical intraepithelial neoplasia (CIN) by two different
cervical specimen collection methods. OBJECTIVES: A cohort of 115 women with a
mean age of 34.6 years (SD 9.1), referred to colposcopy with a history of
abnormal cytology, was studied to compare HPV prevalence and viral load in low
grade CIN vs. high grade CIN. STUDY DESIGN: Prior to the application of acetic
acid, cervical specimens were obtained by either method 1 or 2, as follows:
method 1: A cotton-tipped swab was applied to the ectocervix and endocervix for a
Papanicolaou (Pap) smear. Next, a special cone-shaped cervical brush was applied
to the endocervix, the ectocervix, and to the posterior vaginal vault and
suspended in 1.0 ml of transport medium for HPV testing. Method 2: a Pap smear
was taken with a cyto standard cylindrical cytology brush from the endocervix,
and ectocervix, and the remaining cells were suspended in 3 ml phosphate-buffered
saline (PBS) for HPV testing. Next, a Dacron-tipped swab was used to take a
specimen from the ectocervix and posterior fornix and suspended in the same PBS
solution.
PMID- 9646002
TI - Serious respiratory illness associated with rhinovirus infection in a pediatric
population.
AB - BACKGROUND: Rhinoviruses have long been associated with mild upper respiratory
illness in both adults and children. However, the role of rhinoviruses as lower
respiratory tract pathogens has not been fully characterized. Previous data
suggests that rhinoviruses may cause severe lower respiratory illness in young
children or infants. OBJECTIVES: The present study describes the clinical
presentations, severity of illness and outcomes for a large cohort of pediatric
patients with documented rhinovirus infections. SUBJECTS AND METHODS: A
retrospective chart review was done on 93 pediatric patients from whom 101
nasopharyngeal or endotracheal specimens were positive by viral culture for a
rhinovirus. All patients were hospitalized or seen in the pediatric emergency
department at The Children's Hospital of Philadelphia between 1 January, 1990 and
31 May, 1996. RESULTS: Of the 93 patients, 52 were male and 41 female. The age
range was 0 days to 18 years with 25 (27%) less than 3 months, 42 (45%) between 3
and 12 months and 26 (28%) over the age of 12 months. Clinical presentations on
evaluation in the emergency department or admission included 78 (84%) patients
with acute respiratory illness, 13 (17%) with fever and suspected sepsis and 11
(12%) with other complaints. Reported physical findings on examination included
one or more lower respiratory symptoms or signs of acute distress and fever
greater than or equal to 38.1 degrees C. A total of 64 (69%) children were noted
to have significant past medical histories, including 28 (44%) with prematurity
or complicated neonatal courses, 11 (17%) with prior reactive airways, 8 (12%)
with congenital cardiac disease and 7 (11%) with neurologic disorders. Of the
patients, 29 (31%) were considered to be otherwise healthy children with no
underlying dysfunctions. The mean duration of hospitalization for 69 patients
admitted with respiratory illness who did not develop subsequent unrelated
complications was 3.7 days. No significant bacterial or fungal pathogens were
identified in 91% of the cases. CONCLUSIONS: This study shows that rhinoviruses
were associated with severe lower respiratory illness and hospitalization in a
large pediatric population and that rhinovirus infection was a complicating
factor in those patients with underlying or predisposing conditions.
PMID- 9646003
TI - Rapid detection, culture-amplification and typing of herpes simplex viruses by
enzyme immunoassay in clinical samples.
AB - BACKGROUND: The laboratory diagnosis of herpes simplex infection may require
rapid (direct) tests, as well as cell cultures, for detection of the virus in
clinical samples. The quantity of virus present in clinical samples is variable
and this may depend on the period from onset of rash. In addition, not all
patients may show obvious symptoms with this infection. The successful culture of
herpes simplex virus requires prompt transportation after collection of the
specimen as the virus is easily inactivated. Hence, rapid and culture tests would
enable detection of non-viable and viable viruses. STUDY DESIGN: We describe the
rapid detection of HSV by EIA directly in various clinical samples using
commercially available polyclonal sera. In addition specimens were inoculated in
microwell cell cultures and 4 days post inoculation the culture fluids were
tested for HSV and subtyped by a similar EIA (culture amplified EIA). RESULTS:
The direct EIA showed an endpoint detection of 100 TCID50/ml, sensitivity of 92%
(all specimen types) and specificity of 100%. The direct EIA sensitivity was 97%
in non-genital specimens and 88% in genital specimens. The culture amplified EIA
showed a sensitivity of 95% compared to all confirmed HSV positive samples.
CONCLUSIONS: The results of the HSV rapid tests were available within 24 h from
receipt of specimens. Specimens which were culture negative/direct EIA positive
were confirmed by blocking antisera. Culture positive specimens which were direct
EIA negative were confirmed by subtyping of the virus.
PMID- 9646004
TI - Evaluation of capture ELISA and rapid immunochromatographic test for the
determination of IgM and IgG antibodies produced during dengue infection.
AB - BACKGROUND: Rapid diagnosis of dengue infection is essential to patient
management and disease control. The development of a rapid (5 min)
immunochromatographic test and a 2 h commercial capture enzyme linked
immunosorbent assay (ELISA) for anti-dengue IgM and IgG antibodies may lead to
more rapid and accurate testing in peripheral health settings and diagnostic
laboratories. OBJECTIVES: Evaluate two new commercial tests for dengue serology
(Dengue Rapid test and Dengue Duo ELISA; PanBio, Brisbane, Australia). STUDY
DESIGN: The sensitivity and specificity of the tests were compared with in-house
dengue IgM ELISA and hemagglutination-inhibition (HAI) assays using known
positive and negative dengue specimens, as well as specimens from non-dengue
cases. RESULTS: Both assays showed excellent sensitivity in the diagnosis of both
primary and secondary dengue infection (100%). In both assays, IgG levels showed
excellent correlation with the hemagglutination-inhibition (HAI) assay, and these
could be used to distinguish between primary and secondary dengue infections (92
and 97% of patients correctly classified in the rapid test and Duo ELISA,
respectively). Specificity in both assays was 89% when sera from patients, with
no apparent dengue infection, typhoid, leptospirosis and malaria, were tested.
CONCLUSIONS: These tests should be a useful aid in confirming the clinical
diagnosis of dengue infection. The rapid test will be particularly valuable in
peripheral health settings, while the ELISA has a place in central testing
laboratories.
PMID- 9646005
TI - Evaluation of Puumala virus IgG and IgM enzyme immunoassays based on recombinant
baculovirus-expressed nucleocapsid protein for early nephropathia epidemica
diagnosis.
AB - BACKGROUND: Puumala virus (PUU), a member of Hantavirus genus, is the causative
agent of nephropathia epidemica (NE), a milder form of hemorrhagic fever with
renal syndrome (HFRS). Rapid diagnosis is essential for clinical management of
NE. OBJECTIVES: To evaluate the usefulness of recombinant protein-based IgM
(direct- and mu-capture) and IgG (direct-and antigen (Ag)-capture) enzyme
immunoassays (EIA) in early diagnosis of NE in comparison to IgG
immunofluorescence assay (IF), and to find out the time limit for PUU-specific
antibody seroconversion. STUDY DESIGN: The specific IgM and IgG antibody
responses in serum were analyzed in 109 patients (235 serial sera) and 114
patients (233 serial sera), respectively. The serum panel used was selected from
a larger material according to the availability of information concerning the
date after onset of symptoms, the panel also containing NE patients who had been
IgG-IF negative in their first (early) samples to find out the possible
differences between sensitivities of the EIAs and IF. RESULTS: All NE patients
tested became IgM-positive at the latest on the 6th (mu-capture EIA) or 7th
(direct-IgM EIA) day after onset of symptoms. Out of a panel of very early NE
patient sera (n = 38) that could not be detected by IgG-IF, 66% were already
positive with both direct-IgM EIA and mu-capture EIA. When comparing IgG EIAs and
IgG-IF, 98% of IF-positive sera from NE patients were also positive with direct
IgG EIA, and 99% with Ag-capture IgG EIA. Out of a panel of very early NE-patient
sera (n = 37) that could not be detected by IgG-IF, 57% were positive with direct
IgG EIA, and 27% with Ag-capture IgG EIA. CONCLUSIONS: The baculovirus-expressed
PUU-N-based IgG and IgM EIAs were found most suitable for NE diagnosis, giving
the opportunity in some cases for earlier diagnosis as compared with PUU-IgG IF.
PMID- 9646006
TI - Clinical pharmacokinetics of lornoxicam. A short half-life oxicam.
AB - Lornoxican (chlorotenoxicam) is a nonsteroidal anti-inflammatory drug (NSAID) of
the oxicam class. Unlike other oxicams, lornoxicam has a relatively short plasma
half-life (3 to 5 hours). Lornoxicam is eliminated following biotransformation to
5'-hydroxy-lornoxicam, which does not undergo enterohepatic recirculation.
Glucoroconjugated metabolites are excreted in urine and faeces with a half-life
of about 11 hours. Lornoxicam and its metabolites bind extensively to plasma
albumin. Substantial concentrations of lornoxicam are attained in synovial fluid,
the proposed site of action in chronic inflammatory arthropathies. The effects of
lornoxicam concentration on its therapeutic and toxicological properties have not
yet been extensively reported. Lornoxicam, like other NSAIDs, appears to interact
with warfarin, sulphonylureas, digoxin and furosemide.
PMID- 9646007
TI - Clinical pharmacokinetics of mycophenolate mofetil.
AB - The pharmacokinetics of the immunosuppressant mycophenolate mofetil have been
investigated in healthy volunteers and mainly in recipients of renal allografts.
Following oral administration, mycophenolate mofetil was rapidly and completely
absorbed, and underwent extensive presystemic de-esterification. Systemic plasma
clearance of intravenous mycophenolate mofetil was around 10 L/min in healthy
individuals, and plasma mycophenolate mofetil concentrations fell below the
quantitation limit (0.4 mg/L) within 10 minutes of the cessation of infusion.
Similar plasma mycophenolate mofetil concentrations were seen after intravenous
administration in patients with severe renal or hepatic impairment, implying that
the de-esterification process had not been substantially affected. Mycophenolic
acid, the active immunosuppressant species, is glucuronidated to a stable
phenolic glucuronide (MPAG) which is not pharmacologically active. Over 90% of
the administered dose is eventually excreted in the urine, mostly as MPAG. The
magnitude of the MPAG renal clearance indicates that active tubular secretion of
MPAG must occur. At clinically relevant concentrations, mycophenolic acid and
MPAG are about 97% and 82% bound to albumin, respectively. MPAG at high (but
clinically realisable) concentrations reduced the plasma binding of mycophenolic
acid. The mean maximum plasma mycophenolic acid concentration (Cmax) after a
mycophenolate mofetil 1 g dose in healthy individuals was around 25 mg/L,
occurred at 0.8 hours postdose, decayed with a mean apparent half-life (t1/2) of
around 16 hours, and generated a mean total area under the plasma concentration
time curve (AUC infinity) of around 64 mg.h/L. Intra- and interindividual
coefficients of variation for the AUC infinity of the drug were estimated to be
25% and 10%, respectively. Intravenous and oral administration of mycophenolate
mofetil showed statistically equivalent MPA AUC infinity values in healthy
individuals. Compared with mycophenolic acid, MPAG showed a roughly similar Cmax
about 1 hour after mycophenolic acid Cmax, with a similar t1/2 and an AUC
infinity about 5-fold larger than that for mycophenolic acid. Secondary
mycophenolic acid peaks represent a significant enterohepatic cycling process.
Since MPAG was the sole material excreted in bile, entrohepatic cycling must
involve colonic bacterial deconjugation of MPAG. An oral cholestyramine
interaction study showed that the mean contribution of entrohepatic cycling to
the AUC infinity of mycophenolic acid was around 40% with a range of 10 to 60%.
The pharmacokinetics of patients with renal transplants (after 3 months or more)
compared with those of healthy individuals were similar after oral mycophenolate
mofetil. Immediately post-transplant, the mean Cmax and AUC infinity of
mycophenolic acid were 30 to 50% of those in the 3-month post-transplant
patients. These parameters rose slowly over the 3-month interval. Slow metabolic
changes, rather than poor absorption, seem responsible for this nonstationarity,
since intravenous and oral administration of mycophenolate mofetil in the
immediate post-transplant period generated comparable MPA AUC infinity values.
Renal impairment had no major effect on the pharmacokinetic of mycophenolic acid
after single doses of mycophenolate mofetil, but there was a progressive decrease
in MPAG clearance as glomerular filtration rate (GFR) declined. Compared to
individuals with a normal GFR, patients with severe renal impairment (GFR 1.5
L/h/1.73m2) showed 3-to 6-fold higher MPAG AUC values. In rental transplant
recipients during acute renal impairment in the early post-transplant period, the
plasma MPA concentrations were comparable to those in patients without renal
failure, whereas plasma MPAG concentrations were 2- to 3-fold higher.
Haemodialysis had no major effect on plasma mycophenolic acid or MPAG. Dosage
adjustments appear to not be necessary either in renal impairment or during
dialysis. (ABSTRACT TRUN
PMID- 9646009
TI - Clinical pharmacokinetics of neuromuscular relaxants in pregnancy.
AB - Despite an increased in bodyweight, plasma volume by 45% and blood volume by 35%
that might influence the volume of distribution of polar drugs, the apparent
volume of distribution at steady state (Vss), volume of distribution (Vd) and the
apparent volume of the central compartment (Vc) of atracurium, vecuronium and
pancuronium are unchanged during pregnancy. With an elimination that is
independent of renal, hepatic and enzymatic functions, the clearance of
atracurium is also unchanged. This is corroborated by an unchanged clinical
duration of atracurium during pregnancy. The clearance of pancuronium is
increased by 27% during caesarean section. This may be explained by the increased
glomerular filtration rate reported in pregnant women. The clinical duration of
vecuronium in term and postpartum women is twice that reported in nonpregnant
women. On the other hand, an increase in the clearance clearance of vecuronium
during cesarean sections has been reported. The umbilical/maternal vein
concentration ratio (UV/MV) of nondepolarising neuromuscular relaxants varies
from 7 to 26% and clinical doses of these drugs may induce partial residual
curarisation in neonates. Fetal concentrations of non-depolarising neuromuscular
relaxants are proportional to the maternal dose injected as demonstrated for
pancuronium and vecuronium. Increasing UV/MV with longer drug injection to
delivery intervals have been demonstrated for drugs with a high molecular weight,
such as atracurium, but not for those with a low molecular weight, such as
vecuronium, while conflicting results have been reported for pancuronium. Despite
decreased plasma pseudocholinesterases, the clinical duration of succinylcholine
1 mg/kg is unchanged in pregnant women, and only is slightly increased in
postpartum women. On the other hand, larger doses of succinylcholine have induced
prolonged apnoea and phase II block. The use of a pretreatment dose of a
nondepolarising neuromuscular relaxant to decrease fasciculations and subsequent
postoperative muscle pain is not only unnecessary in pregnant women but may be
hazardous, since it may produce unexpected significant curarisation with
respiratory distress. At clinical doses, transplacental passage of
succinylcholine is insufficient to produce curarisation of neonates except in
those born to mothers with abnormal plasma pseudocholinesterases. Magnesium
sulfate, used in the treatment of pre-eclampsia, will enhance the blocking
effects of nondepolarising neuromuscular relaxants but will have no effects on
the characteristics of paralysis of succinylcholine. Histamine type 2 antagonists
used to decrease the risk of aspiration during induction of anaesthesia do not
influence the blocking properties of neuromuscular relaxants, while
metoclopramide prolongs the block of succinylcholine.
PMID- 9646010
TI - Therapeutic drug monitoring of clozapine treatment. Therapeutic threshold value
for serum clozapine concentrations.
AB - It has been suggested that the minimum effective serum clozapine concentration
for an acceptable clinical response (threshold value) is about 400 micrograms/L.
This article argues against the use of therapeutic drug monitoring (TDM) as a
tool to obtain clozapine concentrations of > or = 400 micrograms/L in the
individual patient from the start of clozapine treatment. The following arguments
are presented: (i) because of a great interindividual variability of the
clozapine concentration to dose ratio (C/D) it can be calculated that extremely
high daily doses (900 to 1800 mg/day) would be necessary in 15% of patients to
obtain a clozapine concentration of 400 micrograms/L; (ii) doses of 200 to 300
mg/day are commonly used in Central Europe. although about 80% of the patients
can be expected to have clozapine concentration < 400 micrograms/L; (iii) in a
double-blind study, no difference in clinical response was found between patients
treated with clozapine in the concentration range of 200 to 300 micrograms/L, and
a group with higher clozapine concentrations; (iv) positron emission topography
(PET) studies indicate that maximum receptor occupancy is obtained at clozapine
concentrations of about 200 micrograms/L and no further receptor occupancy is
obtained by increasing clozapine concentrations to > or = 400 micrograms/L; (v)
the frequency of both severe clozapine-induced adverse effects (seizure and
confusion) and more common adverse effects increases with increasing
doses/clozapine concentrations. It is concluded that the antipsychotic effects
and adverse effects of clozapine occur over a very broad range of serum
concentrations. In most countries the majority of patients are treated with
clozapine concentrations well below the 400 micrograms/L suggested as threshold
concentration for optimum response. Therefore clinical judgement should always be
primarily used for dose adjustments. TDM is useful to follow compliance and to
adjust for extreme serum concentrations and revealing drug interactions.
PMID- 9646012
TI - Mikulas Teich: a biographical sketch.
PMID- 9646013
TI - Business history: Cinderella, prince charming or ugly sister?
PMID- 9646011
TI - Pharmacokinetic optimisation of the treatment of neurocysticercosis.
AB - Neurocysticercosis is the most important parasitic infection of the nervous
system. It is common in communities living in conditions with poor hygiene. Until
the last 2 decades, there was no specific pharmacological treatment: surgery and
corticosteroids were the only medical alternatives. The recent introduction of
anticysticercal drugs, an isoquinoline (praziquantel) and a benzimidazole
(albendazole), has dramatically changed the medical management of
neurocysticercosis. Praziquantel is taken orally and undergoes extensive first
pass hepatic biotransformation. Peak concentration in serum is reached after 1 to
2 hours and the elimination half-life is between 1 and 3 hours. Praziquantel
permeates the blood-brain barrier, thus explaining its effectiveness on
parenchymal brain cysticercosis. Plasma concentrations of the drug are increased
when a high carbohydrate diet is administered. Cimetidine also increases the
plasma concentration of praziquantel by inhibition of cytochrome P450.
Bioavailability of the drug is markedly reduced when given jointly with
antiepileptics or corticosteroids, specially carbamazepine, phenytoin or
dexamethasone. The current schedule for neurocysticercosis treatment lasts 2
weeks at daily doses of 50 mg/kg. Recently, a new therapeutic scheme has been
proposed that considers the pharmacokinetics of the drug. This regime lasts only
1 day and includes 3 dosages of 25 mg/kg at 2-hour intervals. This increases the
time that the parasite is exposed to high drug concentrations. This therapeutic
scheme has produced similar results to longer schemes, with the additional
advantages of cost, length of usual treatments and reduction in total dose
received (being one-tenth of the total dosage). Albendazole is considered by many
as the drug of choice for treatment of neurocysticercosis. It is given orally and
is rapidly and extensively metabolised to albendazole sulfoxide (ALBSO), which is
considered to be the metabolite directly or indirectly responsible for both
toxicity and efficacy outside the gastrointestinal tract. Concentrations of ALBSO
are highly variable between individuals and it has a half-life of between 6 and
15 hours. It also crosses the blood-brain barrier. In patients with extrahepatic
obstruction, the elimination process is prolonged and plasma concentration is
increased. Fatty meals improve absorption. Concomitant administration of
albendazole with dexamethasone or with praziquantel increases plasma
concentration of ALBSO. Albendazole is administered in an 8 day course of 15
mg/kg per day in 2 divided doses 12 hours apart. This scheme, based on drug
pharmacokinetics, has proven to be highly effective. Inflammation is a common
accompaniment of neurocysticercosis; in many cases it is the aetiopathogen
responsible for histological damage. Corticosteroid therapy is useful for
preventing further tissue injury. Long term corticosteroid therapy can be
accomplished with 50 mg of oral prednisone 3 times a week. Acute corticosteroid
therapy includes brief courses with high dosages of intramuscular dexamethasone
or intravenous methylprednisolone. Clinical decisions on cysticidal and anti
inflammatory treatments must be made with the information gathered by
neuroimaging studies, either computed tomography or magnetic resonance, and by
the analysis of cerebrospinal fluid.
PMID- 9646014
TI - Darwin's revolution.
PMID- 9646008
TI - Clinical pharmacokinetics of vasodilators. Part I.
AB - Understanding the mechanism of action and the pharmacokinetic properties of
vasodilatory drugs facilitates optimal use in clinical practice. It should be
kept in mind that a drug belongs to a class but is a distinct entity, sometimes
derived from a prototype to achieve a specific effect. The most common
pharmacokinetic drug improvement is the development of a drug with a half-life
sufficiently long to allow an adequate once-daily dosage. Developing a controlled
release preparation can increase the apparent half-life of a drug. Altering the
molecular structure may also increase the half-life of a prototype drug. Another
desirable improvement is increasing the specificity of a drug, which may result
in fewer adverse effects, or more efficacy at the target site. This is especially
important for vasodilatory drugs which may be administered over decades for the
treatment of hypertension, which usually does not interfere with subjective well
being. Compliance is greatly increased with once-daily dosing. Vasodilatory
agents cause relaxation by either a decrease in cytoplasmic calcium, an increase
in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided
into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors,
angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor
antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids
and NO donors. Despite chemical differences, the pharmacokinetic properties of
calcium antagonists are similar. Absorption from the gastrointestinal tract is
high, with all substances undergoing considerable first-pass metabolism by the
liver, resulting in low bioavailability and pronounced individual variation in
pharmacokinetics. Renal impairment has little effect on pharmacokinetics since
renal elimination of these agents is minimal. Except for the newer drugs of the
dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine,
nisoldipine and nitrendipine, the half-life of calcium antagonists is short.
Maintaining an effective drug concentration for the remainder of these agents
requires multiple daily dosing, in some cases even with controlled release
formulations. However, a coat-core preparation of nifedipine has been developed
to allow once-daily administration. Adverse effects are directly correlated to
the potency of the individual calcium antagonists. Treatment with the potassium
channel opener minoxidil is reserved for patients with moderately severe to
severe hypertension which is refractory to other treatment. Diazoxide and
hydralazine are chiefly used to treat severe hypertensive emergencies, primary
pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors
prevent conversion of angiotensin-I to angiotensin-II and are most effective when
renin production is increased. Since ACE is identical to kininase-II, which
inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a
reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and
cardioreparative effects by preventing and reversing cardiac fibrosis and
ventricular hypertrophy in animal models. The predominant elimination pathway of
most ACE inhibitors is via renal excretion. Therefore, renal impairment is
associated with reduced elimination and a dosage reduction of 25 to 50% is
recommended in patients with moderate to severe renal impairment. Separating
angiotensin-II inhibition from bradykinin potentiation has been the goal in
developing angiotensin-II receptor antagonists. The incidence of adverse effects
of such an agent, losartan, is comparable to that encountered with placebo
treatment, and the troublesome cough associated with ACE inhibitors is absent.
PMID- 9646015
TI - The different faces of science: is genetics a social construct?
PMID- 9646016
TI - Bare heads against red hats: a portrait of Paracelsus.
PMID- 9646017
TI - Science--education and culture. Ideas and concepts of German nineteenth century
scientists.
PMID- 9646018
TI - Thomas George Hodgkins (1803-92) and the future of research at the Royal
Institution (London) and the Smithsonian Institution (Washington).
PMID- 9646019
TI - Biology as technology.
AB - In this paper we have emphasised the technological dimension of the biosciences,
especially the biosciences of our time. As a straight forward fact this dimension
is less controversial than the question of its relevance is. We have argued that
the existence of this dimension is a consequence of the empirical character of
the biosciences (as well as of the sciences in general). Knowledge of nature can
be achieved only if the subject of knowledge is able to gain access to natural
phenomena, and technological means have become increasingly necessary for
achieving this. The more that is already known, the greater the technological
investment required to produce new knowledge. Therefore there is an
interrelationship between the advancement of knowledge and the amount and
complexity of the research technology required. It would be short sighted to
conclude from this observation that human imagination and inventiveness have
become superfluous. Nevertheless the growing preponderance of technological means
for progress in science is undeniable. A particularly important insight is that
this process not only involves a quantitative increase in technology within
science. Our main hypothesis is that there is a close relationship between the
type of means used, the type of subject required for performing research, the
kinds of objects investigated in science, and the nature of the results that are
generated. We have tried to illustrate this by distinguishing between three
different types of bioscience: (a) a descriptive type, (b) an experimental type,
and (c) and an industrial type. Without pretending this provides a universal key
to the history of the biosciences and to understanding of the way science works
today, we hope that such a distinction may open up new avenues of thought. We
hope that this approach will provide us with a more realistic picture of science.
The propositional view reduces science to its theoretical results, in particular
to the theories emanating from basic research. Science is seen as a special kind
of philosophy; its central aim is to provide us with a 'true' view of the world.
Thus the social problems which result from scientific inquiry and from the
application of its results seem to be something external to the very essence of
science and thus only of secondary importance. We believe, therefore, that this
picture of science is both theoretically unsatisfactory and socially misleading.
An appropriate account of science cannot ignore the fact that basic research
represents only a very small part of the science system of our time. It cannot
neglect the fact that science today is steeped with technology and to a great
extent also industrialised. And it cannot treat the social problems of science as
something merely 'external'. To view science as an activity in the sense outlined
in this paper permits one to integrate these different aspects into one coherent
and realistic picture. 1. It is obvious that technology plays a crucial role in
determining the social reality of science. This is mainly because of the high
costs of contemporary research technology that science can no longer be performed
by gentleman scientists like Alexander von Humboldt or Charles Darwin, who not
only financed their own living but the cost of their own research too. Science
today is a profession, and in many cases it can be performed only in large groups
or institutions financed by the state or by private companies. At the same time
this means that it is more and more dependent upon decisions made outside
science. Scientific activities have assumed the economic form of wage labour. The
internal structure of science is characterised by a division of labour and
hierarchical forms of decision making. 2. From a more traditional point this may
seem to be a development 'external' to science, without any relevance for its
'essence'. The aim of science, it may be said, is to discover the truth about the
external world, and the ways of reaching it a
PMID- 9646020
TI - From the "originary phenomenon" to the "system of pelagic fishery": Johannes
Muller (1801-1858) and the relation between physiology and philosophy.
PMID- 9646021
TI - A male mind in a female body: sexology, homosexuality, and the woman question in
Germany, 1869-1914.
PMID- 9646022
TI - The naturalist tradition: a natural history.
PMID- 9646023
TI - Medicine, the body and the botanical metaphor in erotica.
PMID- 9646024
TI - Biology of liberation: some historical aspects of "proletarian race hygienics".
PMID- 9646025
TI - Credit and resistance: Eijkman and the transformation of beri-beri into a vitamin
deficiency disease.
PMID- 9646026
TI - Gout and quackery; or Banks and the mountebanks.
PMID- 9646027
TI - Highlights from the annual meeting of the Association for Molecular Pathology.
PMID- 9646028
TI - Molecular analysis of the p53 gene in pancreatic adenocarcinoma.
AB - Mutations in the p53 tumor suppressor gene are the most common genetic
alterations found in human cancer. Most mutations are accompanied by
stabilization of the protein, which renders the mutations detectable through
immunohistochemical techniques. The immunoreactivity of p53, however, might not
correlate with the result of p53 DNA sequencing. In order to explain the
discrepancy, we studied the p53 expressions, mutations, and changes of the three
dimensional protein structure of mutant p53 in a series of 61 pancreatic
adenocarcinoma specimens using immunohistochemistry, polymerase chain reaction
single strand conformation polymorphism (PCR-SSCP), DNA sequencing, and
computerized protein modeling. PCR-SSCP followed by DNA sequencing of the p53
gene showed mutations in 31.2% (19 of 61) of the pancreatic adenocarcinomas.
Eight of 19 cases showed p53 immunopositivity. These mutations were located on
the surface of the three-dimensional structure or formed unfolded proteins, which
were easily recognized by the antibody. Among other mutations in which p53 was
immunonegative, five cases with deletions and insertion caused frameshift and
formation of severely truncated p53 protein structures unreactive with the
antibody used. In three cases with point mutations, the mutant amino acids were
located in the core of the tightly packed beta sandwich inaccessible to the
antibody. Three silent mutations were immunonegative, corresponding with the
absence of amino acid changes. These results strongly suggest that the analysis
of a computer-generated p53 three-dimensional model based on DNA sequencing data
can assist in evaluating the significance of p53 immunostaining and mutations for
clinical applications.
PMID- 9646029
TI - Detection of tyrosinase mRNA in formalin-fixed, paraffin-embedded archival
sections of melanoma, using the reverse transcriptase in situ polymerase chain
reaction.
AB - Most studies of the reverse transcriptase in situ polymerase chain reaction
technique have reported results from assessments of cultured cells, frozen
sections, and cytospin preparations. For application to routine diagnosis, it
will be necessary to adapt the technique for use with formalin-fixed, paraffin
embedded tissues, the materials that are generally available. We have evaluated
the feasibility of such an approach, using surgical pathology archival material
from 25 UCLA patients: 15 tissues from primary and metastatic melanoma, 7 from
nonmelanocytic tumors, including cancer of the lung, colon, kidney and skin and a
thyroid adenoma, and 3 nontumorous tissues. Seven of 15 melanoma tissues gave a
strong positive signal, 5 gave a weak signal, and 3 were negative. None of the 10
nonmelanoma tissues gave a positive signal. The specific reaction product was
mainly located in the cytoplasm. None of the nonmelanocytic tumors or normal
tissues demonstrated this pattern of cytoplasmic staining. Some nonspecific
nuclear staining was observed in melanocytic and nonmelanocytic tumors and must
not be overread as a true positive result. It is possible to detect tyrosinase
mRNA in formalin-fixed, paraffin-embedded tissue sections of melanoma, but the
technique remains too demanding for routine application.
PMID- 9646030
TI - Translocation (X;18) in a biphasic synovial sarcoma with morphologic features of
neural differentiation.
AB - The authors report a recurred neoplasm showing distinctive histologic,
immunophenotypic, and ultrastructural features characteristic of biphasic
synovial sarcoma with neural differentiation. The features include areas with a
growth pattern of densely packed spindle cells in irregularly intersecting, broad
fascicles, diffuse vimentin and HBA 71 immunoreactivity, expression of S-100
protein, and other neural markers. Moreover, areas with glandular structures and
cellular expression of cytokeratin and epithelial membrane antigen were noted.
Additionally, areas of neural-like growth pattern were positive for neuron
specific enolase, HNK-1, and protein gene product 9.5. Furthermore, cytogenetic
analysis, two-color interphase fluorescence in situ hybridization, and reverse
transcription polymerase chain reaction demonstrated the reciprocal translocation
between chromosomes X and 18 associated with the different subtypes of tumor
cells. The establishment and characterization of the tumor cell line are
detailed. This cell line retains the distinct morphologic and genetic
characteristics of the original biphasic synovial sarcoma with neural
differentiation.
PMID- 9646031
TI - Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell
tumor.
AB - We report two cases of desmoplastic small round cell tumor (DSRCT) with novel
molecular variants of the specific EWS-WT1 gene fusion. This fusion usually
encodes a chimeric RNA with an in-frame junction of exon 7 of EWS to exon 8 of
WT1. In one variant patient, the EWS-WT1 fusion transcript contained an in-frame
junction of exon 9 of EWS to exon 8 of WT1. Moreover, in this patient the tumor
arose in the hand, an extremely unusual site for DSRCT. In the second patient, an
in-frame junction of exon 10 of EWS to exon 8 of WT1 was present. These two cases
of DSRCT show that the molecular variability in the EWS breakpoint observed in
the EWS-FLI1 fusion of Ewing's sarcoma can occur in DSRCT as well. This type of
heterogeneity is relevant to the interpretation of molecular diagnostic assays
and could also affect the functional properties of the encoded chimeric
transcription factors.
PMID- 9646032
TI - Molecular diagnosis of Ewing tumors: improved detection of EWS-FLI-1 and EWS-ERG
chimeric transcripts and rapid determination of exon combinations.
AB - Most Ewing tumors (ET), including Ewing sarcomas, peripheral primitive
neuroectodermal tumors (PNET), and Askin's tumors, can be defined according to
the specific chromosomal translocations t(11;22)(q24;q12) (EWS-FLI-1) or
t(21;22)(q21;q12) (EWS-ERG). Detection of the chimeric RNA transcripts by reverse
transcriptase-polymerase chain reaction (RT-PCR) has greatly facilitated the
diagnosis of ET. Because of variable chromosomal breakpoint locations, however,
the EWS gene fusions with FLI-1 and ERG genes are highly heterogenous, resulting
in different sizes of the amplification products. To improve the diagnostic
usefulness of the RT-PCR assay, we have developed an assay to detect chimeric
mRNA transcripts by nested RT-PCR, followed by digestion of the PCR fragments
with three different restriction endonucleases. This allows confirmation of the
specificity of the PCR product and provides a rapid method to determine the
combination of exons present in a transcript. In the 12 Ewing tumors tested, five
different exon combinations were detected. In nine repeat biopsies of four
patients, the case-specific translocation remained unchanged. One additional
central PNET had no ET-specific translocation. In conclusion, the suggested
combination of RT-PCR and restriction analysis of the PCR products allows a rapid
and specific determination of ET-specific translocations.
PMID- 9646033
TI - Neuroendocrine differentiation in Ewing's sarcomas and primitive neuroectodermal
tumors revealed by reverse transcriptase-polymerase chain reaction of
chromogranin mRNA.
AB - Ewing's sarcomas (ESs), primitive neuroectodermal tumors (PNETs), and
neuroblastomas (NBs) are closely related neoplasms supposedly derived from the
neural crest and belonging to the family of the small blue round cell tumors of
infancy and childhood. We investigated the expression of the neuroendocrine and
neuroectodermal markers chromogranin A (CgA) and secretogranin II (SgII) in ESs,
PNETs, and NBs, both in primitive tumors (five, nine, and four cases,
respectively) and in established cell lines (three ES and two PNET cell lines).
Different technical approaches, namely immunohistochemistry, Northern blot
analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR) were used
in parallel. Chromogranin A and secretogranin II production was constantly
detectable in NBs by all procedures. CgA mRNA was detectable in most ESs and
PNETs only by RT-PCR, whereas SgII mRNA was detectable in some ESs and PNETs by
Northern blot analysis and in all tumors by RT-PCR. CgA and SgII proteins were
never detectable by immunohistochemistry in ESs and PNETs. We conclude that
neuroendocrine differentiation is shared by all three tumor entities, being more
overt in NBs and rudimentary in ESs and PNETs; traces of chromogranin mRNA are
detectable only by a highly sensitive RT-PCR procedure.
PMID- 9646034
TI - Expression of macrophage migration inhibitory factor in the human prostate.
AB - The expression of macrophage migration inhibitory factor (MIF) in prostate tissue
was investigated by immunohistochemistry (IHC), enzyme-linked immunosorbent assay
(ELISA), and Northern blot analysis using a prostate tissue bank. MIF expression
was examined in each of the following established prostate tissue categories:
prepubertal, pubertal, adult normal, benign hyperplastic (BPH), focal carcinoma
within the prostate, and metastatic prostate cancer. IHC showed that all samples
tested were positive for MIF protein, which localized to the glandular epithelial
cells with no apparent staining of stroma. The most intense staining was observed
in the metastatic prostatic adenocarcinoma and the human prostatic adenocarcinoma
cell line LNCaP. Using quantitative ELISA, MIF expression was found to be at
least three times higher in metastatic adenocarcinoma than in normal, BPH, or
focal carcinoma in the adult prostate. This study is the first to report that
prostate glandular epithelial cells express MIF. The exact role of MIF in
prostate development and disease progression requires further study.
PMID- 9646035
TI - p53 mutations in chondrosarcoma.
AB - Chondrosarcoma is a primary bone tumor that has several different grades and
variants. We evaluated 48 chondrosarcomas for p53 overexpression and p53
mutations. p53 expression was evaluated with immunohistochemistry using
monoclonal antibodies PAb421, PAb1801, and PAb240. p53 mutations were identified
with single-strand conformational polymorphism (SSCP) and DNA sequencing in
selected cases. Immunohistochemistry revealed nuclear staining with PAb421 and
PAb1801 in the spindle cell portion of one dedifferentiated chondrosarcoma. SSCP
analysis was abnormal only in the case with positive immunostaining and localized
the mutation to exons 7 and 8. DNA sequence analysis identified a point mutation
of G to C in codon 276, resulting in an amino acid substitution of proline for
alanine. This point mutation has been reported previously in other tumors but not
in chondrosarcoma. Assimilation of our results with previous studies suggests
that p53 mutations are present in a minority of chondrosarcomas but when present,
are in higher grade chondrosarcomas and their variants.
PMID- 9646036
TI - Frequent loss of heterozygosity at chromosome 13q12-13 with BRCA2 markers in
sporadic male breast cancer.
AB - Molecular genetic analysis indicates that the BRCA2 gene plays an important role
in familial male breast cancer. To determine a possible involvement of this tumor
suppressor gene in sporadic male breast cancer, we examined 30 sporadic male
breast carcinomas for loss of heterozygosity (LOH) at two loci on chromosome
13q12-13, a region that spans the BRCA2 locus. Sixteen of 24 (67%) informative
cases showed LOH in at least one marker on chromosome 13q12-13. The affected
cases included both invasive ductal carcinomas and other types of invasive breast
carcinoma and were detected preferentially in patients who were 50 years or
older, in patients with lymph node metastasis, and in progesterone receptor
negative cases. We report, for the first time, a high frequency of LOH at
chromosome 13q12-13 in sporadic male breast cancer and its association with
factors indicating a poor prognosis for this tumor (e.g., lymph node metastasis
and negative progesterone receptor status). These findings suggest an important
role for BRCA2 in the development and progression of sporadic male breast cancer.
PMID- 9646037
TI - Detection of molecular changes in primary intraocular lymphoma by microdissection
and polymerase chain reaction.
PMID- 9646038
TI - Children's health and the environment: a new agenda for prevention research.
AB - Patterns of illness in American children have changed dramatically in this
century. The ancient infectious diseases have largely been controlled. The major
diseases confronting children now are chronic and disabling conditions termed the
"new pediatric morbidity"--asthma mortality has doubled; leukemia and brain
cancer have increased in incidence; neurodevelopmental dysfunction is widespread;
hypospadias incidence has doubled. Chemical toxicants in the environment as well
as poverty, racism, and inequitable access to medical care are factors known and
suspected to contribute to causation of these pediatric diseases. Children are at
risk of exposure to over 15,000 high-production-volume synthetic chemicals,
nearly all of them developed in the past 50 years. These chemicals are used
widely in consumer products and are dispersed in the environment. More than half
are untested for toxicity. Children appear uniquely vulnerable to chemical
toxicants because of their disproportionately heavy exposures and their inherent
biological susceptibility. To prevent disease of environmental origin in
America's children, the Children's Environmental Health Network (CEHN) calls for
a comprehensive, national, child-centered agenda. This agenda must recognize
children's vulnerabilities to environmental toxicants. It must encompass a) a new
prevention-oriented research focus; b) a new child-centered paradigm for health
risk assessment and policy formulation; and c) a campaign to educate the public,
health professionals, and policy makers that environmental disease is caused by
preventable exposures and is therefore avoidable. To anchor the agenda, CEHN
calls for long-term, stable investment and for creation of a national network of
pediatric environmental health research and prevention centers.
PMID- 9646039
TI - Programming for responsiveness to environmental antigens that trigger allergic
respiratory disease in adulthood is initiated during the perinatal period.
AB - Allergy to airborne environmental antigens (allergens) is a major cause of asthma
in children and adults. This review argues that the development of allergen
specific immunologic memory of the type that predisposes to allergy development
is the end result of a T-cell selection process operative during infancy, which
is triggered via encounters between the immature immune system and incoming
airborne allergens from the environment. In normal individuals this process leads
to the development of allergen-specific T-memory cells that secure the T helper
(Th)-1 pattern of cytokines, which actively suppress the growth of their allergy
inducing Th-2 cytokine-secreting counterparts. However, these protective allergen
reactive Th-1 memory cells fail to develop in some individuals, permitting the
subsequent proliferation of allergen-specific Th-2 cells that can trigger
allergic reactions. Recent evidence suggests that genetic predisposition to
allergy may be due in part to hyperactivity of control mechanisms operative in
utero and which normally protect the fetoplacental unit against the toxic effect
of Th-1 cytokines.
PMID- 9646040
TI - Genetic predispositions and childhood cancer.
AB - This article provides an overview of the problem of genetic susceptibility to
childhood cancer with a particular emphasis on problems with ascertaining
inherited cancer risk and the role of tumor-suppressor gene mutations in cancer
predispositions. The association between neurofibromatosis type 1 and childhood
leukemia is used to illustrate some of the issues faced by molecular biologists
and genetic epidemiologists in identifying and analyzing at-risk individuals. The
problem of incomplete penetrance in cancer susceptibility is presented and
potential models are discussed. The article concludes with a number of tentative
conclusions from existing data and speculations for future studies.
PMID- 9646041
TI - Developmental neurotoxicology of endocrine disruptors and pesticides:
identification of information gaps and research needs.
AB - There is increasing evidence that some environmental chemicals can interrupt
neurodevelopmental processes during critical periods of development, resulting in
effects on sensory, motor, and cognitive function. It is now generally accepted
that developing organisms are differentially sensitive to chemical exposure
because of toxicokinetic and/or toxicodynamic factors. Regulatory mechanisms have
been implemented to protect humans from over- or inappropriate exposures to
environmental chemicals. Current regulatory practices, however, may be
insufficient because of the possibility that some environmental chemicals
interfere with endocrine function at key periods of neurodevelopment. In
addition, a recent National Research Council (NRC) report on pesticide
contamination in the diets of infants and children concluded that current
regulatory practices may not sufficiently protect infants and children from the
risk of pesticide exposure. The NRC report indicates that regulatory agencies
might underestimate the actual exposure of infants and children to pesticides and
rely too heavily on data from adults in the risk assessment of pesticides.
Consideration of endocrine-disrupting chemicals and the differential
susceptibility of infants and children has led to identification of a number of
information gaps and research needs that should be addressed in order to improve
future risk assessments for these chemicals.
PMID- 9646042
TI - Biomarkers in pediatric environmental health: a cross-cutting issue.
AB - It is not yet known the extent to which the environment adversely affects the
health of the developing individual. Difficulties in this determination are the
problems of a) the assessment of exposure, b) the long latency of many diseases
induced by the environment, c) the number of confounding exposures, and d) the
extrapolation of animal models to critical stages of human development.
Biomarkers have the potential to be quantitative dosimeters of exposure and
biologic effective dose, as well as early warning signals of biologic effect.
Biomarkers may document interindividual susceptibilities, as well as defining
critical windows of exposure. To be useful, biomarkers need to be validated in
terms of their specificity and sensitivity. Biomarkers are useful across all
disciplines including asthma and respiratory problems, developmental
neurotoxicity, childhood cancer, and endocrine disruptors. Biomarkers have not
been developed nor used widely in pediatric environmental health. Research by our
group and others has documented the validity of biomarkers in pediatric
environmental health. Advances in the field of biomarkers may have important
implications for the detection, prevention, and treatment of environmentally
induced diseases in children. Ongoing validation of promising biomarkers should
be a research priority.
PMID- 9646043
TI - Genes and the environment: their impact on children's health.
AB - Because the human population is biologically diverse and genetically
heterogeneous, it is not surprising that differences in susceptibility to disease
among individuals with or without exposure to environmental agents exist.
Individuals vary greatly in their susceptibility to disease. This is true of
adults and children. The etiologies of many diseases of childhood are due to a
combination of factors, including genetic susceptibility and environmental
exposures during vulnerable periods of development. Genes regulate cellular
growth and development, DNA replication and repair, the metabolism of endogenous
agents in the body, and the metabolism and excretion of exogenous agents that the
body comes in contact with in the environment. This regulation varies over the
life span, contributing to the cellular consequences of the environmental
exposures. This paper summarizes the contributions of genetics in understanding
the etiology of environmentally induced diseases in children. The use of
biomarkers of genetic susceptibility in the study of these diseases will be
discussed. Future research needs for expanding our knowledge of the interactions
between genetic and environmental components of childhood diseases will be
presented.
PMID- 9646044
TI - Relationship between ambient air pollution and DNA damage in Polish mothers and
newborns.
AB - Industrialized regions in Poland are characterized by high ambient pollution,
including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry
and home heating. In experimental bioassays, certain PAHs are transplacental
carcinogens and developmental toxicants. Biologic markers can facilitate
evaluation of effects of environmental PAHs on the developing infant. We measured
the amount of PAHs bound to DNA (PAH-DNA adducts) in maternal and umbilical white
blood cells. The cohort consisted of 70 mothers and newborns from Krakow, Poland,
an industrialized city with elevated air pollution. Modulation of adduct levels
by genotypes previously linked to risk of lung cancer, specifically glutathione S
transferase MI (GSTM1) and cytochrome P4501A1 (CYP1A1) Msp restriction fragment
length polymorphism (RFLP), was also investigated. There was a dose-related
increase in maternal and newborn adduct levels with ambient pollution at the
women's place of residence among subjects who were not employed away from home (p
< or = 0.05). Maternal smoking (active and passive) significantly increased
maternal (p < or = 0.01) but not newborn adduct levels. Neither CYP1A1 Msp nor
GSTM1 polymorphisms was associated with maternal adducts. However, adducts were
significantly higher in newborns heterozygous or homozygous for the CYP1A1 Msp
RFLP compared to newborns without the RFLP (p = 0.04). Results indicate that PAH
induced DNA damage in mothers and newborns is increased by ambient air pollution.
In the fetus, this damage appears to be enhanced by the CYP1A1 Mspl polymorphism.
PMID- 9646045
TI - Approaches to environmental exposure assessment in children.
AB - An improved understanding of the contribution made by environmental exposures to
disease burden in children is essential, given current increasing rates of
childhood illnesses such asthma and cancer. Children must be routinely included
in environmental research. Exposure assessment, both external (e.g., air, water)
and internal dose (e.g., biomarkers), is an integral component of such research.
Biomarker measurement has some advantages that are unique in children. These
include assessment of potentially increased absorption because of behaviors that
differ from adults (i.e., hand-to-mouth activity); metabolite measurement, which
can help identify age-related susceptibility differences; and improved assessment
of dermal exposure, an important exposure route in children. Environmental
exposure assessment in children will require adaption of techniques that are
currently applied in adult studies as well as development of tools and validation
of strategies that are unique for children. Designs that focus on parent-child
study units provide adult comparison data and allow the parent to assist with
more complex study designs. Use of equipment that is sized appropriately for
children, such as small air pumps and badge monitors, is also important. When
biomarkers are used, biologic specimens that can be obtained noninvasively are
preferable. Although the current need is primarily for small focused studies to
address specific questions and optimize research tools, the future will require
establishment of large prospective cohorts. Urban children are an important study
cohort because of relatively high morbidity observed in the urban environment.
Finally, examples of completed or possible future studies utilizing these
techniques are discussed for specific exposures such as benzene, environmental
tobacco smoke, aflatoxin, volatile organic compounds, and polycyclic aromatic
hydrocarbons.
PMID- 9646046
TI - A partnership study of PCBs and the health of Mohawk youth: lessons from our past
and guidelines for our future.
AB - This paper describes a research partnership between the people of Akwesasne and
researchers from the State University of New York at Albany for the study of
polychlorinated biphenyls and the health of Mohawk youth. The study is
distinctive because its goals have been set by the scientists and the community
members and is being conducted jointly by these groups. The research partnership
recognizes the history of relationships between native and nonnative peoples,
particularly scientists, and seeks not only to fulfill certain scientific goals
but to further community ones as well. The relationship is based on three
principles: mutual respect, mutual equity, and mutual empowerment. These
principles guided every aspect of the research process. The project goals were
determined jointly to maximize data quality and minimize the intrusion of
research activities into the lives of community members. Data collection is
performed by research assistants who received extensive and ongoing training in
data collection methods, and who are members of the community. Feedback
procedures were designed by community members and scientists jointly to maximize
understanding. Feedback regarding individuals' pollutant levels and assessments
of growth and development are provided to each individual. Information about
community pollutant levels are provided to the community. Hypothesis testing is
carried out by research scientists, and the results presented first at a
community meeting. Research conducted in this way--as a partnership--requires
more communication, discussion, and travel, but the result is mutual satisfaction
and growth.
PMID- 9646047
TI - Prenatal methylmercury exposure and children: neurologic, developmental, and
behavioral research.
AB - Mercury is present in the earth's crust and is methylated by bacteria in aquatic
environments to methylmercury (MeHg). It is then concentrated by the food chain
so predatory fish and sea mammals have the highest levels. Thus, consuming
seafood leads to exposure. MeHg readily crosses the placenta and the blood-brain
barrier and is neurotoxic. The developing fetal nervous system is especially
sensitive to its effects. Prenatal poisoning with high dose MeHg causes mental
retardation and cerebral palsy. Lower level exposures from maternal consumption
of a fish diet have not been consistently associated with adverse
neurodevelopmental outcomes. However, most studies have considerable uncertainty
associated with their results. Two large controlled longitudinal studies of
populations consuming seafood are underway that are likely to determine if any
adverse effects can be identified. No adverse associations have been found in the
Seychelles, where exposure is mainly from fish consumption. In the Faroe Islands
where exposure is primarily from consumption of whale meat and not fish, adverse
associations have been reported. The Seychelles population consumes large amounts
of marine fish containing MeHg concentrations similar to commercial fish in the
United States. Current evidence does not support the hypothesis that consumption
of such fish during pregnancy places the fetus at increased neurodevelopmental
risk.
PMID- 9646049
TI - Linking research and policy to ensure children's environmental health.
AB - The U.S. Environmental Protection Agency (U.S. EPA) has made protecting
children's environmental health its highest priority. Data on how and when
children may be at risk are vital for accomplishing this goal. Recent examples of
the link between research and policy include U.S. EPA actions to carry out the
recommendations of the National Academy of Sciences on pesticides in children's
food, reduce and prevent childhood lead poisoning, and revise national ambient
air quality standards for ozone and particulate matter. Today, the Food Quality
Protection Act (FQPA), which makes protecting children from pesticide residues in
food a national priority, is contributing to the growing need for data for
decision making. Further impetus comes from provisions in the FQPA and 1996 Safe
Drinking Water Act Amendments for establishing a screening and testing program
for potential risks from endocrine disruptors. Another factor is the analysis
that will be required under President William J. Clinton's executive order
directing all federal agencies, for the first time, to reduce environmental
health and safety risks to children. Success of the U.S. international commitment
to protect children is directly tied to the strength and availability of
environmental data. To meet such challenges, the U.S. EPA is revising key science
policies, expanding research opportunities, and adding to the public's right-to
know tools. In this dynamic climate, there are growing opportunities for the
research community to play a greater role in helping ensure the well-being of
children living today and in generations to come.
PMID- 9646048
TI - Environmental health sciences education--a tool for achieving environmental
equity and protecting children.
AB - Children are highly susceptible to deleterious effects of environmental toxins.
Those who live in underserved communities may be particularly at risk because
environmental pollution has been found to be disproportionately distributed among
communities. Mounting evidence suggests that asthma rates are rising and that
this disease can be caused or aggravated by air pollution. Although ambient air
quality has generally improved, these improvements have not reached minority
communities in equal proportions. This and other data has fueled the concept of
environmental justice or environmental equity, which has led to community
activism and government actions. One possible example of environmental inequity
and its consequences is the Hunt's Point community, in the South Bronx, New York.
This community experiences a high pollution burden with the siting of facilities
that emit hazardous wastes into the air. Our approach to this problem has been
the formation of mechanisms for bidirectional communication between community
residents, government entities, and academic institutions such as Mount Sinai
Medical Center. As a result of this experience, we believe that the key to
achieving environmental health, especially in communities of color where many
children are at risk, is to empower residents to take charge of their environment
by providing relevant educational opportunities. Strategies for environmental
health education include multitiered training approaches that include community
residents, parent education, direct children education, and community education
through professional counselors and train-the-trainer approaches. We propose that
academic researchers must use community residents not just as subjects of our
studies, but to increase our mutual understanding of environmental health,
resulting in active participation of community members in research design, data
collection, analysis, and dissemination of results in order to make intervention
strategies more effective.
PMID- 9646050
TI - The U.S. EPA Conference on Preventable Causes of Cancer in Children: a research
agenda.
AB - On 15-16 September 1997, the U.S. Environmental Protection Agency sponsored the
Conference on Preventable Causes of Cancer in Children. The conference was
convened to examine rising trends in reported incidence of childhood cancer and
the association of these trends with environmental exposures. This paper
summarizes recommendations for future research offered by participants. These
recommendations included more collaborative research integrating epidemiology,
molecular biology, toxicology, and risk assessment; the development of better
protocols for toxicologic testing including carcinogenicity using young animals;
and research focused on specific periods of development during which
susceptibility to environmental agents may be enhanced. Also recommended was
enhanced use and development of molecular biomarkers for identification of
susceptible populations, and documentation of exposures and effects in
epidemiologic and toxicologic studies. Although toxicologic testing is considered
essential to determine the effects of potential carcinogens on biological
organisms, participants emphasized the need to link these findings with
epidemiologic and exposure assessment research.
PMID- 9646051
TI - Chemicals and children's environment: what we don't know about risks.
AB - Although we know that certain types of childhood cancers are increasing, we do
not know why. With few exceptions, we know little about the role of environmental
carcinogens in childhood cancer. Generally, we have adequate information to
screen chemicals for potential hazard for only certain categories of chemicals-
drugs, food additives, and pesticides. The U.S. Environmental Protection Agency
(U.S. EPA) is implementing the 1996 Food Quality Protection Act, which provides
added protections against pesticide risks, especially for children. But the
situation is quite different for many industrial chemicals. We lack even basic
toxicity data for a majority of the U.S. EPA's list of approximately 3000
nonpolymeric high-production-volume industrial chemicals being produced in the
United States each year that are found in consumer products and the workplace. We
know even less about the remaining 70,000 chemicals on the U.S. EPA inventory.
The U.S. EPA has initiatives underway to address the risks posed by some of these
commercial chemicals, including efforts to reduce risks posed by indoor air
pollutants and household products. These initiatives specifically address
children's risks. We are supporting toxicity screening of high-volume industrial
chemicals on a cooperative international basis through the Organisation for
Economic Co-operation and Development. Until more information is available, it is
difficult to assess the possible role of these chemicals in childhood cancer and
to take steps to reduce exposure to children.
PMID- 9646052
TI - Methodologic approaches to studying environmental factors in childhood cancer.
AB - Little is known about environmental causes of childhood cancer. This is probably
due to the relative rarity of cancer in children. In the United States, cancer
incidence in adults is over 20 times greater than cancer incidence in children.
The situation is compounded by the fact that two groups of cancers, leukemias and
brain and spinal tumors, account for half of all childhood cancers. The rarity of
childhood cancer renders the conduct of most cohort studies infeasible. The
majority of studies assessing potential environmental risk factors for childhood
cancers have been case-control studies, which are highly efficient for studying
rare diseases. Case-control studies of childhood cancers have been greatly
facilitated by using cooperative clinical trial groups for case identification.
The national studies that have emerged utilize random-digit telephone dialing and
telephone interviewing as feasible and economic means of identifying and
interviewing controls. Other approaches such as descriptive epidemiology,
ecologic studies, and studies of cancer clusters have proven to be disappointing
in elucidating environmental causes of childhood cancer. Descriptive and ecologic
studies provide no information on specific exposures of study subjects; rather,
they use population levels as surrogates for individual exposure. Studies of
cancer clusters have also proven to be disappointing. Although there are numerous
difficulties in conducting research on the causes of childhood cancer, these
difficulties can be remedied by using carefully designed and conducted studies.
It should be remembered that the epidemiologic approach is probably the most
likely research venue for uncovering environmental causes of childhood cancer.
PMID- 9646053
TI - Results from an international case-control study of childhood brain tumors: the
role of prenatal vitamin supplementation.
AB - An international case-control study of primary pediatric brain tumors included
interviews with mothers of cases diagnosed from 1976 to 1994 and mothers of
population controls. Data are available on maternal vitamin use during pregnancy
for 1051 cases and 1919 controls from eight geographic areas in North America,
Europe, and Israel. Although risk estimates varied by study center, combined
results suggest that maternal supplementation for two trimesters may decrease
risk of brain tumor (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5-0.9),
with a trend of less risk with longer duration of use (p trend = 0.0007). The
greatest risk reduction was among children diagnosed under 5 years of age whose
mothers used supplements during all three trimesters (OR 0.5, CI 0.3-0.8). This
effect did not vary by histology and was seen for supplementation during
pregnancy rather than during the month before pregnancy or while breast feeding.
These findings are largely driven by data from the United States, where most
mothers took vitamins. The proportion of control mothers who took vitamins during
pregnancy varied tremendously: from 3% in Israel and France, 21% in Italy, 33% in
Canada, 52% in Spain and 86 to 92% at the three U.S. centers. The composition of
the various multivitamin compounds taken also varied: the daily dose of vitamin C
ranged from 0 to 600 mg, vitamin E ranged from 0 to 70 mg, vitamin A ranged from
0 to 30,000 IU, and folate ranged from 0 to 2000 micrograms. Mothers also took
individual micronutrient supplements (e.g., vitamin C tablets), but most mothers
who took these also took multivitamins, making it impossible to determine
potential independent effects of these micronutrients.
PMID- 9646054
TI - Pesticides and childhood cancer.
AB - Children are exposed to potentially carcinogenic pesticides from use in homes,
schools, other buildings, lawns and gardens, through food and contaminated
drinking water, from agricultural application drift, overspray, or off-gassing,
and from carry-home exposure of parents occupationally exposed to pesticides.
Parental exposure during the child's gestation or even preconception may also be
important. Malignancies linked to pesticides in case reports or case-control
studies include leukemia, neuroblastoma, Wilms' tumor, soft-tissue sarcoma,
Ewing's sarcoma, non-Hodgkin's lymphoma, and cancers of the brain, colorectum,
and testes. Although these studies have been limited by nonspecific pesticide
exposure information, small numbers of exposed subjects, and the potential for
case-response bias, it is noteworthy that many of the reported increased risks
are of greater magnitude than those observed in studies of pesticide-exposed
adults, suggesting that children may be particularly sensitive to the
carcinogenic effects of pesticides. Future research should include improved
exposure assessment, evaluation of risk by age at exposure, and investigation of
possible genetic-environment interactions. There is potential to prevent at least
some childhood cancer by reducing or eliminating pesticide exposure.
PMID- 9646055
TI - Parental occupational exposures and risk of childhood cancer.
AB - Occupational exposures of parents might be related to cancer in their offspring.
Forty-eight published studies on this topic have reported relative risks for over
1000 specific occupation/cancer combinations. Virtually all of the studies
employed the case-control design. Occupations and exposures of fathers were
investigated much more frequently than those of the mother. Information about
parental occupations was derived through interviews or from birth certificates
and other administrative records. Specific exposures were typically estimated by
industrial hygienists or were self-reported. The studies have several limitations
related to the quality of the exposure assessment, small numbers of exposed
cases, multiple comparisons, and possible bias toward the reporting of positive
results. Despite these limitations, they provide evidence that certain parental
exposures may be harmful to children and deserve further study. The strongest
evidence is for childhood leukemia and paternal exposure to solvents, paints, and
employment in motor vehicle-related occupations; and childhood nervous system
cancers and paternal exposure to paints. To more clearly evaluate the importance
of these and other exposures in future investigations, we need improvements in
four areas: a) more careful attention must be paid to maternal exposures; b)
studies should employ more sophisticated exposure assessment techniques; c)
careful attention must be paid to the postulated mechanism, timing, and route of
exposure; and d) if postnatal exposures are evaluated, studies should provide
evidence that the exposure is actually transferred from the workplace to the
child's environment.
PMID- 9646056
TI - Tissue injury by reactive oxygen species and the protective effects of
flavonoids.
AB - Reactive oxygen species contribute decisively to a great variety of diseases.
Flavonoids are benzo-gamma-pyrone derivatives of plant origin found in various
fruits and vegetables but also in tea and in red wine. Some of the flavonoids,
such as quercetin and silibinin, can effectively protect cells and tissues
against the deleterious effects of reactive oxygen species. Their antioxidant
activity results from scavenging of free radicals and other oxidizing
intermediates, from the chelation of iron or copper ions and from inhibition of
oxidases. For their free radical scavenging properties, scavenging of lipid- and
protein-derived radicals is presumably of special importance. A non-radical
reactive oxygen species effectively trapped by flavonoids is hypochlorous acid.
In general, the antioxidative properties of flavonoids are favoured by a high
degree of OH substitution. On the other hand, inhibition of enzymatic functions
other than oxidases, e.g., inhibition of lipoxygenase and thus prevention of the
formation of leukotrienes, may also participate in the cell and tissue protective
properties of flavonoids.
PMID- 9646057
TI - YM022, a highly potent and selective CCKB antagonist inhibiting gastric acid
secretion in the rat, the cat and isolated rabbit glands.
AB - We investigated the effects of the novel CCKB/gastrin antagonist YM022 on gastric
acid secretion in vivo and in vitro, compared to CI-988 and L365,260 as reference
antagonists. In the anaesthetized rat, pentagastrin-induced stimulation of
gastric acid secretion was dose-dependently and up to 100% inhibited by i.v.
administration of YM022 with an ID50 of 0.009 +/- 0.0006 mumol/kg h in comparison
to 0.6 +/- 0.03 and 3.40 +/- 0.05 mumol/kg h for CI-988 and L-365,260,
respectively. In the gastric fistula cat, i.v. administration of YM022 produced a
similar inhibitory effect with an ID50 of 0.02 mumol/kg in comparison to 1.6 and
2.5 mumol/kg for CI-988 and L-365,260, respectively. Furthermore, bolus injection
of 0.6 mumol/kg YM022 produced 100% inhibition within 30 min and 85% inhibition
was still observed after 3 h. In the isolated rabbit gastric glands, CCK8
stimulated 14C-aminopyrine uptake was inhibited according to the following rank
order of potency: YM022 (IC50 = 0.0012 microM) > > CI-988 (IC50 = 0.2 microM) > >
L365,260 (IC50 = 2.8 microM). Unlike with L365,260, no influence of CI-988 and
YM022 on histamine-stimulated acid output was shown in this study. Thus, YM022 is
a highly potent and selective gastric CCKB/gastrin receptor antagonist and has a
long-lasting inhibitory effect on gastric acid secretion.
PMID- 9646058
TI - Physical activity, skeletal muscle beta-adrenoceptor changes and oxidative
metabolism in experimental chronic heart failure.
AB - In chronic heart failure (CHF), changes in sympathetic nervous activity and
skeletal muscle metabolism contribute to a limitation in the capacity for
exercise. The aim of this study was to investigate the potential relationships
between physical deconditioning, skeletal muscle beta-adrenoceptor (beta-AR)
characteristics and muscle metabolic changes in rats with coronary ligation
induced experimental CHF. Muscle beta-AR and norepinephrine levels were assessed
in rats with CHF that had been treated with propranolol at 28 mg/kg/day and
compared with rats with CHF that had not been treated and those that had
undergone sham operations. The soleus muscle was investigated because of its
predominantly oxidative fibre-type composition. Measurements of spontaneous
locomotion activity were carried out using telemetry. After 85 days, muscle
energetic phosphate levels were assessed using 31P-magnetic resonance
spectroscopy. The phosphocreatine resynthesis rate was decreased in the untreated
CHF rats (15 +/- 3 vs 33 +/- 5 mmol L-1 min-1 in the sham-operated rats, p <
0.05), but this had been partially reversed in the rats given propranolol (22 +/-
3 mmol L-1 min-1, non-significant (NS) when compared with the sham-operated
rats). Spontaneous activity did not differ among the three groups of animals.
Soleus beta-adrenoceptor density was decreased in rats with CHF (8.8 +/- 3.0
fM/mg of protein vs 22.0 +/- 7.0 fM/mg of protein in the sham-operated rats, p <
0.05) and normalized in the propranolol-treated rats (31.9 +/- 7.0 fM/mg of
protein, NS vs the sham-operated rats; p < 0.05 vs the untreated rats with CHF).
Unchanged spontaneous activity in the rats with CHF suggests that physical
deconditioning could not account for the muscle metabolic changes. Changes in
skeletal muscle energy metabolism were accompanied by changes in beta-AR density,
occurring in typically oxidative beta-AR-rich muscles, reversible after beta
blocker therapy and therefore suggestive of beta-AR downregulation.
PMID- 9646059
TI - Beneficial hemodynamic effects of nicorandil in a canine model of acute
congestive heart failure: comparison with nitroglycerin and cromakalim.
AB - Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and
cromakalim (CRM) were examined in a canine model of acute congestive heart
failure (CHF). CHF was produced by injections of saponin into coronary arteries
of anesthetized dogs followed by volume loading and continuous i.v. infusion of
methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt
and myocardial segment shortening (SS) markedly decreased, while the left
ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and
the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and
CRM (n = 8), which were administered i.v. after production of CHF, caused a
comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but
NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly
reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as
well as systemic hemodynamic indices to those observed with i.v. NCR despite
distinct coronary vasodilation. These results indicate that NCR may exert
beneficial hemodynamic effects in an experimental CHF mainly due to lessening
both afterload and preload rather than the coronary vasodilating effect.
PMID- 9646060
TI - Inhibitory effects of tacrine and physostigmine on catecholamine secretion and
membrane currents in guinea-pig adrenal chromaffin cells.
AB - The effects of tacrine and physostigmine on catecholamine secretion induced by
veratridine and high K+, and on voltage-dependent Na+ and Ca2+ currents, were
investigated in guinea-pig adrenal chromaffin cells. In perfused adrenal glands,
tacrine (100 microM) caused an inhibition of veratridine-induced catecholamine
secretion, but physostigmine (100 microM) did not. In dispersed cells, both
tacrine (1 microM-1 mM) and physostigmine (1 microM-1 mM) decreased catecholamine
secretion induced by veratridine in a dose-dependent manner. The inhibitory
effect of tacrine was much greater than that of physostigmine. Tacrine alone at a
high concentration (such as 1 mM) caused a substantial increase in catecholamine
secretion by itself and completely abolished the veratridine-induced secretory
response in dispersed cells. High-concentration physostigmine showed a similar
effect, but to a much lesser extent. The high K+ (46.2 mM)-evoked catecholamine
secretion from dispersed cells was not affected by tacrine (1-100 microM) or
physostigmine (1 microM-1 mM). In fura-2 loaded cells, tacrine (100 microM)
almost abolished [Ca2+]i rise induced by veratridine, but only slightly reduced
that evoked by high K+. In voltage-clamped cells, tacrine (300 microM) depressed
the voltage-dependent Na+ and Ca2+ current by about 93% and 69%, and
physostigmine (300 microM) depressed them by about 30% and 17%, respectively.
These results suggest that tacrine decreases the veratridine-induced
catecholamine secretion primarily by inhibiting the voltage-dependent Na+
channels rather than the Ca2+ channels. Physostigmine acts in a manner similar to
tacrine, but its potency is much lower than that of tacrine.
PMID- 9646061
TI - Passage of S-(+)- and R-(-)-ketoprofen across the human isolated perfused
placenta.
AB - Ketoprofen is a chiral non-steroidal anti-inflammatory drug (NSAID) available as
a racemic (rac) mixture of S-(+)- and R-(-)-isomers. Its inhibitory effect on
prostaglandin biosynthesis resides virtually in the S-form. Interestingly, R
ketoprofen does not undergo substantial metabolic inversion in humans. Though
contraindicated during the last trimester of pregnancy, NSAIDs, including
ketoprofen, are used as tocolytic agents in some cases. The S/R plasma
concentration ratio was reported to average 2.3 in premature neonates whose
mothers were given rac-ketoprofen and to be close to 1 in the maternal plasma.
Thus, we investigated the placental transfer of rac-ketoprofen in vitro using
Schneider's perfused human cotyledon model. Glucosed Earle solutions with and
without human serum albumin (HSA) were used. Several maternal perfusates were
tested with different rac-ketoprofen concentrations together with 20 mg L-1 of
antipyrine as a reference substance. Ketoprofen enantiomers were assayed by a
specific HPLC method with derivatization procedure. HSA concentrations in
maternal perfusate influenced the placental transfer of ketoprofen enantiomers.
In the absence of HSA in the maternal perfusate, the S-(+)/R-(-) concentration
ratio was close to 1 in the fetal perfusate. By contrast, this ratio averaged
1.44 after addition of HSA 10 g L-1 on the maternal side. Similar results were
found for dialysis experiments using an inert Spectrapor 2 membrane suggesting
that the S-(+)-free concentration is superior to the R-(-)-free concentration in
the presence of HSA. Direct measurements of the free concentrations by
centrifugal ultrafiltration confirmed this hypothesis. Accordingly, the data
observed in vivo may result, at least in part, from the stereoselective protein
binding of ketoprofen.
PMID- 9646062
TI - Effect of a single oral dose of two erythromycin ethylsuccinate formulations on
gastric emptying in healthy volunteers: a scintigraphic study.
AB - Macrolides are potential gastrokinetic agents. The purpose of this study was to
assess the effect of a single oral dose of two erythromycin formulations on
gastric emptying of the solid and liquid phases in twelve healthy volunteers and
to seek a correlation between pharmacokinetic parameters and changes in gastric
emptying. The gastric emptying times of liquids and solids were measured
simultaneously by means of a scintigraphic technique after a single oral
administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline
erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover
study in three separate weeks. Blood samples were obtained for erythromycin
assay. The two oral formulations induced a similar acceleration of gastric
emptying. When compared to the placebo, both erythromycin preparations
significantly shortened the gastric transit time of solids and liquids
(respectively 30% and 20% on average, p < 0.01). The incidence of
gastrointestinal side-effects was similar with the two erythromycin forms and the
placebo. No correlation was found between the peak serum erythromycin
concentrations and the solid or liquid gastric half-lives. With the amorphous
formulation, the area under the plasma time-concentration curves was small and
solid and liquid gastric emptying were strongly accelerated, pointing to a direct
effect on the gastrointestinal smooth muscle.
PMID- 9646063
TI - Organisation of a clinical trial unit--a proposal.
AB - The urgent need for the performance of more, better designed, and better
conducted randomised clinical trials is increasingly recognised. Based on
structured interviews with leading persons of 43 outstanding organisations and
units involved in clinical trials in Europe and North America during 1993, ways
of organising and staffing clinical trial units were investigated. The present
proposal is based on this experience from which an attempt to extract a composite
set of minimal requirements has been made regarding pertinent objectives and
aims, organisational aspects, staffing, and estimated costs of establishing a
clinical trial unit. The core staff is suggested to consist of two chief
physicians, one statistician, one data manager, one project coordinator, and two
secretaries. In order to fulfil the minimal requirements for running such a unit,
it is calculated that about GBP 450,000 per year is needed to cover investments,
core staff, and running costs, but excluding housing costs and costs of
randomised clinical trials that do not originate from trial coordination. In
return, such a unit should be able to mount and launch 6-7 multicenter randomised
clinical trials during a 5 year period, corresponding to a total cost for
coordination per trial of about GBP 340,000. However, with a larger staff more
studies may be coordinated possibly reducing the cost per trial depending on
greater effectiveness in utilisation of the basic facilities.
PMID- 9646064
TI - Clinical and epidemiological characteristics of juvenile myocardial infarction in
Italy: the GISSI experience.
AB - BACKGROUND: No clinical and epidemiological data are available about acute
myocardial infarction (AMI) at a young age in large populations, due to the low
prevalence of AMI in younger people. The aim of the present study is to analyze
epidemiological and clinical characteristics of AMI among younger people in
Italy, using the data bases of the three GISSI studies. METHODS: Analysis of
epidemiological and clinical characteristics of AMI according to different age
groups in the three GISSI studies that collected data from 1985 to 1993. RESULTS:
In the GISSI-2 and GISSI-3 data bases, the prevalence of AMI at a young age (2
and 1.8% respectively; difference -0.2% with 95% CI from -0.4 to 0.3%), hospital
mortality (2.3 and 1.9% respectively; difference -0.4% with 95% CI from -1.9 to
1.0%), and the rate of young female patients (8 and 7% respectively; difference
1% with 95% CI from -3.6 to 1.6%) are similar. In the GISSI-2 study, we observed
that in comparison to elderly patients (> 70 years) young patients (< 40 years)
are more frequently smokers (83.9 vs 21.0%; difference 62.9% with 95% CI from
58.5 to 67.3%) and have a higher rate of family history for CAD (42.1 vs 21.1%;
difference 21.0% with 95% CI from 15.3 to 26.7%) and of hypercholesterolemia
(28.3 vs 15.0%; difference 13.3% with 95% CI from 18.5 to 80.8%), but show a
lower prevalence of hypertension (12.2 vs 44.3%; difference from -32.1% with 95%
CI from -28.0 to -36.2%) and diabetes (2.9 vs 18.8%; difference -15.9% with 95%
CI from -13.5 to -18.3%). AMI at a young age is generally the first event in
ischemic heart disease; in comparison with older patients with previous AMI (6.4
vs 17.4%; difference -11.0% with 95% CI from -7.8 to -14.0%) and history of
angina (23.2 vs 40.0%, difference -16.8% with 95% CI from -11.8 to -21.9%) this
is less frequent. The rate of complications is lower in younger as opposed to
older patients for both early (7.7 vs 31.2%; difference -23.5% with 95% CI from
20.0 to -26.9%) and late heart failure (2.9 vs 18.5%; difference -15.6% with 95%
CI from -13.2 to -18.0%), as well as for angina (6.4 vs 10.5%; difference -4.1%
with 95% CI from -1.1 to -7.1%), reinfarction (1.0 vs 3.3%; difference -2.3% with
95% Ci from -1.1 to -3.6%) and complete AV block (1.6 vs 6.6%; difference -5.0%
with 95% CI from -3.3 to -6.7%). In young patients, we observed lower in-hospital
(1.6 vs 21.1%; difference -19.5% with 95% CI to -21.6%) and six-month mortality
(1.3 vs 8.1%; difference -6.8% with 95% CI from -5.0 to -8.5%). CONCLUSIONS: The
incidence and mortality of AMI at a young age was steady during the period
between 1988 and 1993. AMI at a young age is a clinical entity with specific
characteristics that differ from those found in old patients. In addition, it has
peculiar risk profile with a better short- and medium-term outcome.
PMID- 9646065
TI - [The Italian Journal of Cardiology, the English language and culture].
PMID- 9646066
TI - Assessment of right ventricular function and interstitial fibrosis in idiopathic
dilated cardiomyopathy: hemodynamic correlates and prognostic value.
AB - BACKGROUND: Right ventricular (RV) function and morphometric quantitation of
interstitial fibrosis in idiopathic dilated cardiomyopathy (IDC) have not been
the subject of specifically designed clinical observations. In particular, their
role in routine assessment and prognostic evaluation of patients (pts) with IDC
remains to be settled. METHODS: Eighty-one consecutive IDC patients (63 M, 18 F;
mean age 52 +/- 11 yrs) with left ventricular (LV) systolic dysfunction
(angiographic ejection fraction - EF - < 55%), normal coronary arteries and no
histologic evidence of myocarditis were studied. Cardiac catheterization and
endomyocardial biopsy (EMB) were routinely performed in all cases. RV volumes and
EF were obtained by angiography according to Ferlinz' method and interstitial
fibrosis was quantitated by computer-assisted morphometric analysis. These data
were analyzed in order to study correlations with hemodynamic parameters and to
assess their prognostic value in a long-term follow-up. RESULTS: In the study
population, right ventricular EF was significantly lower than in normal controls
(35 +/- 11% vs 53 +/- 6%, p < 0.0001) and showed a significant positive
correlation with LV EF (r = 0.54; p < 0.0001), and a weak but significant
negative correlation with fibrosis (r = -0.29; p = 0.03). RV volumes, but not EF,
were significantly related to mean pulmonary pressure. At multivariate analysis,
RV end-diastolic volume (EDV) and EF were the two independent predictors of
severe heart failure (NYHA class III-IV). After a mean follow-up of 64 +/- 36
months, 20 pts died and 9 had heart transplantation, for a 63% transplant-free
survival rate (TFS). Multivariate analysis identified three independent
predictors of TFS: LV stroke work index (p < 0.0001), RV stroke work index (p =
0.02) and RV EDV (p = 0.03). Fibrosis was predictive of survival only in the
subgroup with LV EF < 20%. CONCLUSIONS: Assessment of RV function provides useful
information in the evaluation of hemodynamic profile and prognosis of pts with
IDC. Quantitation of interstitial fibrosis by morphometry provides little
additional data.
PMID- 9646067
TI - Doppler echocardiographic assessment of left ventricular isovolemic relaxation
flow.
AB - BACKGROUND: It is not infrequent to observe a peculiar intraventricular
relaxation flow (IRF) pattern during the isovolumic relaxation time (IRT),
especially in patients (pts) with left ventricular hypertrophy (LVH). This is
even more likely in pts with hypertrophic obstructive cardiomyopathy and in VVI
paced pts. Despite these observations, the prevalence and clinical relevance of
this finding have not been evaluated thoroughly and systematically in a
consecutive series of patients. METHODS: Ninety-two consecutive pts underwent a
conventional Doppler echo study for the evaluation of systolic and diastolic
function (fractional shortening, EF, E and A wave velocity, duration and ratio,
and IRT). of these, 42 pts had LVH, 14 had mitral regurgitation (MR) with
depressed EF, 8 had CAD with depressed EF and 28 were normal subjects. IF was
searched for during the evaluation of IRT and its duration, velocity and integral
were measured when noted. RESULTS: Fifty-six patients (61%) showed an IRF at
Doppler examination. Of these, fifteen were normal subjects (53%) and 34 (81%, p
= 0.03 vs normal) were hypertensive pts. Among pts with depressed EF, only two of
14 with MR and 5 of 8 with no MR showed an IRF (14 vs 62%; p = 0.032). When
evaluating LV function, we observed that pts with an IRF had a larger atrial
filling fraction, a longer isovolumic relaxation time and a higher ejection
fraction with respect to pts with no IRF (respectively, 40 +/- 13% vs 30 +/- 13%,
p = 0.005; 108 +/- 23 ms vs 77 +/- 22 ms, p = 0.0001; 70 +/- 14% vs 61 +/- 16%, p
= 0.01). CONCLUSIONS: Our data confirm that IRF may be observed in healthy
subjects and may be due to an asynchronous relaxation of the LV during IRT, in
consideration of a higher prevalence of a greater atrial filling fraction in pts
with IF as compared to those in whom this Doppler signal is absent. Moreover, IRF
is more frequent in pts with LVH and is rare in pts with MR (predominantly due to
a very short isovolumic relaxation time).
PMID- 9646068
TI - Relation between white blood cell count and several risk factors for coronary
heart disease in patients with systemic hypertension.
AB - BACKGROUND: Several epidemiological studies have shown a relation between white
blood cell (WBC) count in peripheral blood samples and other cardiovascular risk
factors. Such associations have also been described in patients affected by
dyslipidemia. On the other hand, no data are available in patients with systemic
hypertension. AIM: In a southern Italian population of hypertensive patients, in
order to assess the relation between WBC count and other risk factors for
coronary artery disease; in addition, to evaluate if a high WBC count can
identify subgroups of hypertensives with a higher risk profile for
atherosclerosis. POPULATION AND METHODS: We evaluated 147 consecutive patients
(44 males, mean age 49 +/- 11 years) with a minimum 2-year history of systemic
hypertension in the absence of ischemic heart disease and cerebrovascular
disease. Among risk factors, we considered: hypercholesterolemia,
hypertriglyceridemia, hyperglycemia and obesity. RESULTS: WBC count was
significantly higher in patients with 2 or more risk factors (7.092 +/- 1034
cells/dl than in hypertensives without risk factors (5.902 +/- 1167, p < 0.0001).
WBC count was significantly associated with hyperglycemia (p < 0.001), number of
cigarettes smoked daily (p < 0.004), fibrinogen plasma levels (p < 0.008) and
azotemia (p < 0.009). Multivariate analysis has shown a positive significant and
independent relation between WBC count and both hyperglycemia and number of
cigarettes. CONCLUSIONS: These results emphasize that, among hypertensives,
subgroups with a higher WBC count also have a higher risk profile for
atherogenesis. The relation between WBC and some risk factors is confirmed by our
data in a population of patients affected with systemic hypertension.
PMID- 9646069
TI - [Role of stress myocardial perfusion scintigraphy in the follow-up of patients
undergoing coronary angioplasty: comparison between qualitative and semi
quantitative analysis].
AB - In order to assess the diagnostic accuracy of stress/rest myocardial perfusion
scintigraphy in the follow-up of patients undergoing percutaneous transluminal
coronary angioplasty (PTCA) we studied 50 patients (pts) before and 6 months
after PTCA. All patients underwent control coronary angiography and then were
divided in 2 groups, according to angiographic evidence of restenosis (25 pts) or
no restenosis (25 pts). Myocardial perfusion imaging was performed with 99mTc
methoxy-isobutyl-isonitrile (MIBI). For MIBI scans, both qualitative and semi
quantitative analysis were performed. SPECT images were displayed on a color
monitor in random order and graded blindly by 2 experienced observers. Rest and
stress MIBI uptake was scored using a 4-point scale (ranging from 0 = normal, to
3 = absence of uptake). Individual subjects' perfusion scores were calculated by
adding the individual segments' scores. History of relapsing angina showed a
sensitivity and specificity of 76 and 96%, respectively. Exercise testing and
MIBI tomoscintigraphy exhibited sensitivity and specificity of 80 and 56%, and 92
and 44%, respectively. However, when considering semiquantitative data and
comparing them with pre-PTCA studies, specificity of MIBI scan increased to 96%,
while sensitivity decreased to 72%. The results of the present study confirm high
sensitivity and low specificity for both exercise ECG and myocardial perfusion
scintigraphy, in the detection of restenosis following PTCA. However, when
performing semiquantitative analysis of perfusion scanning and comparison with
pre-PTCA images, the specificity of MIBI tomoscintigraphy increases
significantly. Therefore, when adopting myocardial perfusion scintigraphy for the
follow-up of patients undergoing PTCA, a pre-revascularization scan should be
obtained as often as possible. This approach, in the context of a positive test,
makes feasible the assessment of often partial improvements in perfusion of the
myocardium relative to the treated vessel, consequently avoiding many false
positive results which invariably lead to coronary angiography.
PMID- 9646070
TI - [Myocardial revascularization with both internal mammary arteries].
AB - BACKGROUND: The excellent results obtained with the use of the left internal
mammary artery (IMA) for myocardial revascularization have led to the
simultaneous use of other arterial conduits, particularly the right IMA. METHODS:
The present study includes the first 100 consecutive patients with ischemic heart
disease who underwent myocardial revascularization with in situ bilateral IMA
grafted to branches of the left coronary artery, performed at our center. Ninety
six (96%) were males and four (4%) were females, with a mean age of 58 +/- 8
years (range, 35-75 years). The main indication for myocardial revascularization
was angina in 83 patients (83%) and heart failure in 17 (17%). Seventy patients
had three-vessel disease. RESULTS: Hospital mortality was 1%, with one death due
to left ventricular failure. Three patients had perioperative myocardial
infarction, six experienced ventricular arrhythmia, two had acute renal failure
and nine respiratory insufficiency. Dehiscence of the sternal wound occurred in
four patients, evolving in mediastinitis in one. All discharged patients were
checked after 26 +/- 6 months (range, 12-38 months). There were two deaths, one
because of cardiac failure and one sudden death, with a two-year survival rate of
97 +/- 2%. Five patients (5%) required hospitalization because of angina, and the
angiographic study showed stenosis/occlusion of one or both IMAs in four cases.
Thirty-five (38%) of the remaining patients underwent a coronarographic (25
patients) or transthoracic Doppler study (10 patients) to evaluate patency of the
IMAs. The patency index was 100% for the left IMA and 94% for the right IMA.
CONCLUSIONS: Myocardial revascularization with bilateral IMA in situ can be
performed with low hospital mortality and morbidity. Sternal dehiscence is the
worst complication and appears to be more frequent in diabetic and elderly
patients. Mid-term results are satisfactory, with a good survival rate and
freedom from major cardiac events. However, a longer follow-up is necessary to
better appreciate the advantages of myocardial revascualarization with in situ
bilateral IMAs.
PMID- 9646071
TI - [Rapid resolution of ST-segment elevation predicts functional recovery in acute
myocardial infarction treated with primary percutaneous transluminal coronary
angioplasty].
AB - OBJECTIVES: This study was designed to prospectively assess the ability of the 12
lead electrocardiogram (ECG) and optimal ECG criteria to predict late functional
recovery in patients with acute myocardial infarction (AMI) treated with primary
coronary angioplasty (PTCA) BACKGROUND: A simple clinical method to predict
clinical outcome in patients with reperfused AMI is highly desirable from a
clinical point of view. METHODS: Seventy-five patients with AMI treated with
successful PTCA (TIMI flow grade 3 and residual stenosis < 30%) underwent serial
12-lead ECG before PTCA and every hour for the first 6 hours and then at 9, 12,
and 18 hours after PTCA. All patients underwent two-dimensional echocardiography
before PTCA and 1 and 6 months later for the evaluation of regional wall motion.
The ST segment level in the lead exhibiting the maximal ST elevation (ST increase
max) and the sum of the ST segment elevation (sigma ST increases) were calculated
on initial ECG and a cut-off values of > or = 50% reduction of ST increases max
sigma ST increases elevation and sampling intervals were correlated with late
functional recovery. A wall motion score index (WMSI: 1 = normal to 4 =
dyskinesia) and 16-segment model were used. Reversible dysfunction was defined as
a decrease of > or = 0.22 in WMSI. RESULTS: At univariate analysis a > or = 50%
reduction of both ST increases max and sigma ST increases was related to late
functional recovery. Multiple logistic regression analysis revealed that
reduction of sigma ST increases was the most powerful predictor of late
functional recovery (p = 0.008). A > or = 50% reduction of sigma ST increase
within 4 hours of PTCA provided the optimal criterion for predicting late
functional recovery. CONCLUSIONS: Rapid reduction of sigma ST increases elevation
is an accurate predictor of left ventricular functional recovery in patients with
AMI treated with primary PTCA. Optimal criteria include a reduction in sigma ST
increases elevation > or = 50% within 4 hours of PTCA.
PMID- 9646072
TI - A rare anatomic variation of the anomalous origin of all three major coronary
arteries from the right sinus of Valsalva.
AB - We describe the case of a patient with angiographic evidence in the right sinus
of Valsalva of anomalous origin of LCx and common origin of LAD and RCA. This
anomaly, which has not been reported previously, represents a further anatomic
variation of the rare anomalous origins of all coronary arteries from right sinus
of Valsalva. The symptoms in our patients were related exclusively to the
atherosclerotic lesions in LCx and RCA and not to the anatomic anomalies. The
patient underwent a bypass graft to LCx and RCA.
PMID- 9646073
TI - [Massive pulmonary embolism after blunt chest trauma: considerations on
pathogenesis and therapy].
AB - A blunt chest trauma may provoke many different kinds of cardiac injury,
particularly myocardial contusion, sometimes causing subsequent acute myocardial
infarction or cardiac arrest by ventricular tachyarrhythmia in the absence of
structural lesions. We describe a case of acute massive pulmonary embolism after
a blunt chest impact caused when the patient was kicked by a horse. The patient
showed progressive dyspnea three days after the trauma. The diagnosis was reached
by non-invasive means and finally confirmed by pulmonary angiography. Because of
the contraindication to thrombolytic therapy, we performed percutaneous catheter
and guide-wire clot fragmentation with at least partial immediate success and
subsequent favorable course. We discuss possible pathophysiological mechanisms to
explain this case, which has no precedents in the literature.
PMID- 9646074
TI - [Clocking diagnostic and therapeutic procedures in coronary care unit patients:
analysis of clinical performance times].
AB - BACKGROUND: An optimal use and exploitation of professional personnel is of
paramount importance for health management organizations, as human resources are
both their greatest asset and heaviest financial burden. To better understand the
amount of medic and paramedic work and time required for the typical diagnostic
and therapeutic procedures in a coronary-care unit setting, we measured their
average times and analyzed their inherent co-factors. METHODS: This study was
conducted on 206 consecutive coronary-care unit patients. These patients were
divided into subgroups according to their admission diagnosis: acute myocardial
infarction, unstable angina, acute cardiac failure, pulmonary embolism or other
pathologies. Each subgroup was then subdivided even further according to the
severity of their clinical status. Diagnostic and therapeutic procedures
("macroactivities") have been identified and each one was subdivided into sub
procedures ("microactivities"). All microactivities were carefully clocked in
every patient in order to calculate the average execution time for every
macroactivity. RESULTS: Our data show that myocardial infarction patients and, in
general, a more severe clinical status required a longer stay in the coronary
care unit. Again, longer overall clinical performance times were necessary in
myocardial infarction patients as compared to the unstable angina subgroup. There
were no statistically significant differences among other subgroups. More
severely ill patients required longer clinical performance times because of both
a longer coronary-care unit stay and longer clinical performance time per day.
More than half of the total clinical performance time for each patient was spent
during the first two days. Paramedics supplied more than 80% of the total
performance time. CONCLUSIONS: The authors undertook a study of typical coronary
care unit clinical activities by clocking the performance times of the usual
diagnostic and therapeutic procedures. The data thus obtained come from direct
measurements and describe the clinical performance of both medics and paramedics
in a real-life setting. This could thus be used as a yardstick to verify current
workload standards. It is hoped that a deeper understanding of these activities
will optimize the full exploitation of available human resources.
PMID- 9646075
TI - [Role of cardiac first aid in a level-II Emergency Department].
AB - We report our experience in the organization and management of a Cardiac First
Aid Unit (CFAU) which was developed according to the guidelines of the National
Hospital Cardiologists Association as a part of a General Emergency Department.
The CFAU is a 24 hour service directed by a Senior Cardiologist. The medical
facilities are two monitored beds for short-term observation (cardio-pulmonary
resuscitation instruments, echocardiograph, endoesophageal pacing for overdrive).
The main goals of CFAU are the treatment of cardiac emergencies (acute myocardial
infarction, pulmonary oedema, threatening arrhythmias, etc.) and the screening of
patients presenting with chest pain or symptoms suggesting cardio-vascular
involvement. In one year, there were 1700 admissions to the CFAU (3.7% of the
total Medical Emergencies). The frequency of hospital admissions was 81% and
coronary heart disease accounted for 38.3%. A sample of 100 consecutive patients
with acute myocardial infarction admitted in the period October-November 1996 was
examined to explore the impact of a CFAU on in-hospital delay in the application
of thrombolysis. Thirty-nine patients were treated with thrombolysis, 15 in CFAU
and 24 in Coronary Care Unit (CCU). The mean in-hospital delay to thrombolysis
was 30 +/- 14 minutes for those treated in CFAU and 55 +/- 12 minutes for those
treated in CCU (p < 0.0004). In a second sample of 100 consecutive patients with
undetermined chest pain, by means of our protocol of short observation we
identified 22 cases of acute myocardial infarction (AMI), 8 cases of angina
pectoris, 18 various cardiac causes, 30 non-cardiac causes, 22 absent disease.
ECG was obtained in all 100 pts, cardiac enzymes in 74, echocardiogram and chest
X-ray in 48, ST monitoring in 26. In no case was diagnosed AMI after discharge.
Cardiac First Aid Unit, as designed in our Hospital, suits the needs of a level
II Emergency Department. It is a useful tool to shorten in-hospital delay to
thrombolysis and to screen chest pain with nearly complete safety.
PMID- 9646076
TI - [From atherosclerotic plaque to coronary thrombus: pathophysiologic aspects of
acute coronary syndromes].
PMID- 9646077
TI - [Myocardial revascularization using the Vineberg procedure].
PMID- 9646078
TI - [Clarification of "DRG and PRG in infarction"].
PMID- 9646079
TI - [Sudden death in young people with mitral valve prolapse or mitral valve prolapse
in young people who died suddenly].
PMID- 9646081
TI - [Early discharge after myocardial infarction].
PMID- 9646082
TI - Correlation of relative afferent pupillary defect and estimated retinal ganglion
cell loss.
AB - BACKGROUND: The relative afferent papillary defect (RAPD) is an important
parameter for quantifying the loss of neuronal function in asymmetric optic nerve
disease. We wanted to assess its correlation with retinal ganglion cell loss,
estimated from visual field defects, using a recently described method. METHODS:
In 36 patients with unilateral optic nerve disease, the RAPD was measured using
an automated, computerized infrared pupillometer. The percentage of ganglion cell
loss was estimated with clear templates. RESULTS: We found a highly significant
correlation between the RAPD and estimated ganglion cell loss. The correlation
was higher for Humphrey visual fields than for Goldmann visual fields measured
with the 14e and 12e stimulus. CONCLUSION: The RAPD correlates well with
estimated retinal ganglion cell loss in optic nerve disease. Humphrey visual
fields seem to reflect the ganglion cell loss better than Goldmann visual fields.
The spatial distribution of pupillomotor retinal ganglion cells seems to be
proportional to the distribution of light-sensitive ganglion cells projecting to
the lateral geniculate nucleus.
PMID- 9646083
TI - Holmium:YAG thermokeratoplasty: treatment parameters for astigmatism induction
based upon spherical enucleated human eyes.
AB - BACKGROUND: The refractive outcome of thermokeratoplasty for astigmatism
correction depends upon the optical zone diameter (OZD) and coagulation angle
(CA; distance between two coagulation spots around the flat meridian). METHODS:
Astigmatism was induced in 36 spherical human eye-bank eyes (Ho:YAG laser, 15 Hz,
20 mJ/pulse, 25 pulses per coagulation spot) with different OZDs and CAs. Thirty
eyes received free-hand laser application (marked positions). Six eyes were
treated using a suction mask, providing a constant OZD of 8.1 mm and an angle of
22.5 degrees between the laser spots. To compare the results, silicone replicas
of the eyes were made pre- and postoperatively and analyzed by video-topometery.
RESULTS: With an average decrease of 4 D/mm the refractive change is inversely
linear to the OZD. Changes of the CA showed significant variations between 22.5
degrees and 45 degrees, only. Mask guidance leads to the same amount of average
refractive change. The deviation is +/- 3.4 D for the freehand application but
only +/- 0.8 D for mask guidance. CONCLUSION: The data obtained in this in vitro
study are transferred to a treatment nomogram describing the immediate
postoperative refractive change, not identical with the final refraction. The
results of the study are limited by the fact that astigmatism was induced in
spherical corneas, rather than correcting preexisting ones.
PMID- 9646084
TI - Retinal capillary density in patients with arterial hypertension: 2-year follow
up.
AB - BACKGROUND: Arterial hypertension is known to be an important risk factor for
cerebral and cardiovascular disease. Previous studies have demonstrated a
decrease of capillary density in the perifoveal network in tandem with decreased
capillary flow velocity in patients with essential hypertension. In a prospective
study we quantified the retinal microcirculation in order to evaluate the time
course of changes in the perifoveal network. METHODS: Thirty-three patients with
essential hypertension (mean age 45 +/- 14 years) underwent video-fluorescein
angiographic studies at baseline and at 2 years 28 +/- 6 months) thereafter. The
angiograms were obtained with a scanning laser ophthalmoscope and were digitally
recorded. By means of digital image analysis we quantified off-line the mean area
of perifoveal intercapillary areas (PIA) and the mean capillary flow velocity.
RESULTS: At baseline, the patients with hypertension showed significantly
increased PIA and a significantly decreased capillary flow velocity compared with
reference values. During the follow-up period the capillary flow velocity
decreased further significantly, whereas the PIA showed no significant change.
CONCLUSIONS: The continuous decrease of capillary flow velocity demonstrates a
progression of altered microcirculation in patients with essential hypertension
whose blood pressure was believed to be well controlled. Further studies with
this technique may be useful to determine the influence of antihypertensive
therapy and may help to identify patients at risk for cerebrovascular events.
PMID- 9646085
TI - Comparative immunohistochemical oestrogen receptor analysis in primary and
metastatic uveal melanoma.
AB - BACKGROUND: The investigation reported here was carried out to determine the
oestrogen receptor status of metastatic and primary uveal melanomas. METHODS: A
series of 23 primary and 24 metastatic formalin-fixed paraffin-embedded choroidal
melanomas were analysed immunohistochemically with the monoclonal antibody (MAb)
1D5 using the avidin-biotinylated peroxidase method and antigen retrieval with
microwaves. Melanophages were identified with MAb PG-M1 to macrophages. RESULTS:
None of the primary or metastatic melanomas contained tumour cells that would
have shown a nuclear immunoreaction for oestrogen receptors with MAb 1D5.
However, in 20 of the 23 primary tumours and in 14 of the 24 metastases a
variable number of infiltrating cells showed a strong positive cytoplasmic
immunoreaction with MAb 1D5. The cells contained pigmented cytoplasmic granules
that resisted bleaching of melanin and their cytoplasm was strongly labelled with
MAb PG-M1, identifying them as cross-reacting macrophages. CONCLUSION: Oestrogen
receptors can not be used as a prognostic indicator if anti-oestrogen therapy is
considered for treatment of metastatic uveal melanoma. However, because anti
oestrogens also act by other mechanisms on both tumour and host tissues, the lack
of oestrogen receptors does not automatically negate their therapeutic effect in
disseminated melanoma.
PMID- 9646086
TI - Conditions for balance between lower normal pressure control and hypotony in
mitomycin trabeculectomy.
AB - BACKGROUND: Striving for low to ultra-low postoperative intraocular pressure
(IOP) through filtering surgery usually increases the incidence of prolonged
hypotony. Early postoperative prognostic indicators for IOP control to lower
normal level and prolonged hypotony in trabeculectomy with mitomycin C were
examined to determine conditions required to obtain an optimum balance between
them. METHODS: Records of initial trabeculectomy with mitomycin C (0.4 mg/ml, 3
min) in 59 consecutively operated Japanese patients with primary open-angle
glaucoma who had used multiple medications before operation were retrospectively
analyzed. IOP control to lower normal level was defined as having failed if IOP
could not be maintained below 15 mm Hg without medication. Prolonged hypotony was
defined as postoperative IOP below 5 mm Hg for more than 2 months, excluding the
first month. The Cox proportional hazards model was applied to identify early
postoperative factors contributing to the two surgical outcomes. RESULTS: Among
the factors studied, only the mean IOP on postoperative days 9-14 was
significantly correlated with the surgical outcome. A receiver operating
characteristic plot suggested that mean IOP of 8 mm Hg in this period would give
an optimum balance between the two. CONCLUSION: IOP of 8 mm Hg 9-14 days after
surgery may be advisable in patients with preoperative multiple medications in
whom IOP control to lower normal level is attempted with mitomycin C
trabeculectomy. Knowledge of this may be helpful in deciding when laser lysis of
sutures is indicated.
PMID- 9646087
TI - Aqueous flare in retinitis pigmentosa.
AB - BACKGROUND: The purpose of this study was to quantify blood-ocular barrier
impairment by measuring aqueous flare in retinitis pigmentosa (RP) and to search
for clinical correlations. METHODS: Forty-nine patients (94 eyes) with RP and 85
normal controls were examined. Aqueous flare was quantified with the noninvasive
laser flare-cell meter (FC-1000, Kowa, Japan). Degrees of cystoid macular edema
(CME), vitreous pigment dusting (VPD), intraretinal migration of retinal pigment
epithelium, and waxy pallor of the optic nerve head were determined
semiquantitatively by biomicroscopy. Data were analyzed using the t-test the Mann
Whitney U-test, the chi-squared test and regression analysis by taking into
account the dependency of data from two eyes of the same patients. RESULTS:
Aqueous flare (photon counts/ms) was significantly higher in RP (mean 10.11 +/-
3.53) than in normals (3.89 +/- 0.94; P < 0.001). Clinically significant CME was
present in 26% of eyes with RP, being significantly more frequent in autosomal
dominant RP (11 of 16 eyes, 69%) than in other variants (17%; P < 0.005).
Multivariate analysis revealed that CME was most strongly associated with flare
values (r = 0.84), P < 0.01), whereas--after adjusting for CME--correlations
between aqueous flare and other clinical findings did not reach significance.
CONCLUSION: RP eyes show increased aqueous flare values, indicating impairment of
blood-occur barriers. This appears to be associated with CME and with autosomal
dominant RP.
PMID- 9646088
TI - Expression of Fas antigen on helper T lymphocytes in Vogt-Koyanagi-Harada
disease.
AB - BACKGROUND: Our purpose was to analyze the expression of Fas antigen on CD4+
lymphocytes in the aqueous humor (AH) and cerebrospinal fluid (CSF) of patients
with Vogt-Koyanagi-Harada disease (VKH). METHODS: Using three-color flow
cytometry, we assessed T-lymphocyte subsets stained with fluorescence-conjugated
anti-CD3, CD4, CD8, CD29, CD45RA, CD45RO, HLA-DR, and Fas monoclonal antibodies
in AH, CSF and peripheral blood (PB) from 8 patients with active VKH. RESULTS:
CD3+ T cells constituted the majority of lymphocytes in AH and CSF, in contrast
to with PB. The percentages of CD4+ lymphocytes in uveitic AH and CSF were
significantly higher than that in PB (P < 0.01). Activated CD4+ and CD8+ cells
were significantly more frequent in AH than in CSF and PB (P < 0.01). Although
the percentages of CD45RA+ cells within CD4+ cells in AH and CSF were extremely
low compared with those in PB, the proportions of CD29+ and CD45RO+ (memory)
cells within CD4+ were much higher than those in PB (P < 0.01). Fas antigen was
also highly expressed on such CD4+ cells in AH, as in other uveitis patients and
on such cells in CSF. Moreover, the percentages of Fas+ and memory cells in AH
were significantly higher than those in CSF. CONCLUSIONS: The majority of CD4+
lymphocytes in AH and CSF from patients with active VKH were activated memory
cells, on which Fas antigen was also highly expressed. Although this Fas
expression may not be an apoptosis-related phenomenon, accumulation of Fas+
memory T lymphocytes in AH and CSF probably reflects the immunopathologic
mechanism of VKH.
PMID- 9646089
TI - The development of visual pursuit during the first months of life.
AB - BACKGROUND: There are few previous investigations of smooth pursuit in infants.
The aim of our study was to quantify visual pursuit in infants between 1 day and
16 weeks of age. METHODS: Eye movements of 97 healthy infants between 1 day and
16 weeks of age were recorded one to seven times with infrared photo-oculography.
For stimulation of visual pursuit a square of 9.4 deg of visual angle with
vertical gratings moved horizontally at a constant velocity of 7.5 deg/s.
RESULTS: In the first 2 weeks of life, segments of smooth pursuit were measured
with a maximum velocity of 7.93 deg/s, with a maximum gain of 1.06 and a maximal
duration of 3.16 s. In sequential recordings no significant increases of
velocity, gain or duration were found. However, the total time the subjects
followed the stimulus with smooth plus saccadic pursuit increased significantly
with age (from a median of 39.0% to a median of 61.5% of examination time).
CONCLUSION: This study clearly demonstrates that smooth pursuit is already
present in the first week of life. We found no significant increase in velocity,
gain and duration of smooth pursuit segments in the first 16 weeks of life with
our recording technique. However, the total pursuit time, reflecting attention,
increased with age. The ocular machinery to drive pursuit appears to be in place
at birth and seems not to be influenced by increased attention in the first
months of life.
PMID- 9646090
TI - Radiating retinal folds detected by scanning laser ophthalmoscopy using a diode
laser in a dark-field mode in idiopathic macular holes.
AB - BACKGROUND: The pathogenesis of idiopathic macular hole is unclear. We studied
the morphologic features of idiopathic macular holes using a modification of the
scanning laser ophthalmoscope (SLO). METHODS: Seventy-two eyes of 57 patients
with macular hole (40 women, 17 men; age 66.1 +/- 6.4 years, mean +/- SD) were
included in this study. The macular holes were classified according to the Gass
classification (1988). The changes around the macular holes were recorded by SLO
using both a confocal aperture with a helium-neon laser (633 nm) and a ring
aperture (dark-field mode) with a diode laser (780 nm) to detect fine morphologic
features. RESULTS: We successfully observed minute retinal wrinkling, i.e.,
radiating striae (fold type) and a dome configuration (dome type), around the
macular holes using the SLO dark-field mode with a diode laser, which provides a
deeper retinal image because of the longer wave-length laser and the indirect
mode. A helium-neon laser with a confocal aperture sometimes failed to disclose
the fine retinal wrinkles. Most of the stage 2 macular holes were of the fold
type. The smaller the hole, the higher the prevalence of the fold type. As the
holes progressed in size, the prevalence of the dome type increased. The
radiating retinal folds disappeared after successful vitreous surgery.
CONCLUSION: The SLO dark-field mode with a diode laser might be useful for clear
observation of fine retinal features around macular holes. The retinal folds
probably indicate the presence of traction on the macula and hence may be good
markers for macular repair after vitreous surgery.
PMID- 9646091
TI - Peripheral multifocal chorioretinitis with panuveitis: clinical and immunogenetic
characterization in older patients.
AB - BACKGROUND: The etiology of peripheral multifocal chorioretinitis with panuveitis
(MCP) is unclear. Characteristic signs of MCP are punched-out, white
chorioretinal lesions of the lower fundus periphery, chronic smoldering
chorioretinal inflammation, vitritis, and mild inflammation of the anterior
chamber. In this retrospective study we investigated clinical and immunogenetic
abnormalities in MCP in older patients. PATIENTS AND METHODS: 20 patients (18
women, 2 men), median age 70.5 years, were investigated clinically by
ophthalmologists and were typed for HLA class I antigens using the standard
microlymphocytotoxicity test. Typing for HLA-DR antigens was performed by
polymerase chain reaction with sequence-specific primers (PCR-SSP). The HLA
controls consisted of healthy people (108 for HLA class I, 114 for HLA class II).
RESULTS: MCP was bilateral in 18 patients. Disease-related symptoms were present
for 8 months (median) before diagnosis. The main presenting symptoms or findings
were glaucoma (in 11 patients), visual loss (7), iritis (5), and vitritis (2).
Anterior segment changes were frequently seen: keratitic precipitates (32 eyes),
anterior chamber cells (25 eyes), aqueous flare (26 eyes), posterior synechiae
(22 eyes), secondary glaucoma (15 eyes), and iris neovascularization (8 eyes).
All patients had vitritis and typical chorioretinal fundus lesions. Fourteen
patients developed cystoid macular edema (bilateral in seven cases). Subretinal
neovascularization occurred in three patients. Although systemic medication was
given to 17 patients and surgical treatment was performed in 25 eyes, improvement
in vision was found in only 6 eyes, but 18 eyes deteriorated markedly (median 5
lines) during follow-up (median 24.5 months). Immunogenetically significant
reduced frequencies of HLA-B7 and HLA-DR1 were found; also HLD-DR15(2) was
reduced. However, several alleles were increased in MCP, although not
significantly: HLA-A31; HLA-B57, HLA-B62; HLA-Cw3, HLA-Cw6; HLA-DR4, HLA-DR7, and
HLA-DR8. CONCLUSIONS: MCP is clinically and immunogenetically open to
speculation. The present diagnosis and treatment of MCP are insufficient. Further
DNA typing methods should clarify, whether HLA-DQ antigens are associated with
the disease.
PMID- 9646092
TI - Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth
factor.
AB - BACKGROUND: Ocular diseases caused by neovascularization are among the leading
causes of blindness. No specific pharmacological treatment is available. Among
potential drugs, thalidomide deserves special interest since a wide body of
clinical experience exists. However, its antiangiogenic effect is controversial.
We therefore investigated the effect of thalidomide on corneal angiogenesis
induced by vascular endothelial growth factor (VEGF), which has a special role
among angiogenic growth factors. METHODS: Corneal neovascularization was induced
in NZW rabbits by an intrastromal pellet loaded with 500 or 750 ng VEGF. Animals
received two daily feedings of 200 mg/kg thalidomide. RESULTS: Significant
inhibition of corneal angiogenesis (P < 0.0001) was caused by the teratogenic
dose of thalidomide after the 5th day of treatment and persisted for more than 16
days. No obvious side effects were recorded. CONCLUSIONS: Thalidomide has a
significant antiangiogenic effect against VEGF-induced neovasclar growth.
Together with earlier findings this observation indicates that the drug inhibits
two angiogenic pathways which are mediated through integrin adhesion molecules.
PMID- 9646093
TI - A mouse model to study the wound healing response following filtration surgery.
AB - BACKGROUND: Failure of trabeculectomy is attributed to an exaggerated wound
healing response at the episcleral level. We have developed a simple technique in
mice that creates corneoscleral wounds and used it to study the role of growth
factors in wound healing associated with loss of fistular patency. In addition,
the effect of suramin on the wound healing response has been investigated.
MATERIALS AND METHODS: Using black C57B1/6 mice, we created a fistula from the
subconjunctival space to the anterior chamber by external penetration with a 25
gauge needle through the bulbur conjunctiva. Eyes were examined by light
microscopy at different times following surgery and evaluated for the presence of
growth factors in the sclerosing wound by immunohistochemistry. In an additional
group, suramin (1.0 mg/ml) was applied topically five times. RESULTS: The
limbal/scleral wounds closed rapidly. Granulation tissue consisting mostly of
fibroblasts developed within the first 2 days, and the collagen component
increased over time. By 4 weeks, the wound was completely healed. We found that
within 1 day after surgery GF beta 2 reached high intensity. TGF beta 1 and PDGF
A reached maximal intensity by day 2 and remained elevated for about a week, PDGF
B was present at moderate intensity even before surgery. Myofibroblastic
differentiation was observed from days 2 to 7. Suramin-treated wounds showed a
decrease of cells and delay in fibroblast maturation. TGF beta 1 and TGF beta 2
levels persisted longer than in the controls, while PDGF A and PDGF B levels were
lower than in the controls at all time points. CONCLUSIONS: The mouse
corneoscleral wound model that we have developed mimics the process of wound
healing and fistulizing surgery that takes place in other animal models and in
human eyes in which the outcome of the surgery is poor. Our analysis of the
appearance of growth factors associated with wound healing demonstrates that PDGF
A as well as TGF beta 1 and TGF beta 2 appear early in the process at high levels
and are potential targets for interventive strategies to ensure channel patency.
Suramin has a distinct effect on the wound healing process and expression of
growth factors and may be a promising substance for clinical use.
PMID- 9646094
TI - Toxoplasmic retinochoroiditis: resolution without treatment of the perilesional
satellite dark dots seen by indocyanine green angiography.
AB - PURPOSE: Satellite dark dots (SDD) seen by indocyanine green angiography (ICGA)
around the main retinochoroiditis focus are described in 75% of cases. Whether
SDDs represent subclinical infectious foci or just a perilesional inflammatory
reaction is not known. The purpose here was to report a case giving additional
information on this question. METHODS: We analysed the evolution of ICGA SDDs in
a patient with recurrent toxoplasmic retinochoroiditis who received no
antitoxoplasmic treatment because the lesion was located outside the areas where
treatment is classically recommended. RESULTS: The patient had a recurrence of
retinochoroiditis on the nasal aspect of the disc about 2 disc diameters away
from the disc. It was decided to observe the recurrence before introducing
treatment. Diminution of SDDs occurred by 3 weeks after the initial ICGA, and
complete resolution was observed on a follow-up ICG angiogram obtained 8 weeks
after the initial visit. CONCLUSION: Resolution of ICGA SDDs in toxoplasmic
retinochoroiditis seems to occurring a similar fashion whether or not the
retinochoroiditis is treated by anti-toxoplasmic drugs, indicating that SDDs
probably represent a non-infectious perilesional inflammatory reaction.
PMID- 9646095
TI - [Coronary heart disease as inflammatory disease of the vascular bed? Etiology,
sequela or misconception?].
AB - In this editorial the traditional risk factors are contrasted with more recent
modifications of the response to injury theory including the modified LDL
response to injury and the immunological response to injury theories. This issue
of "Herz" is devoted to the missing points in the classic risk factor concepts
and revisits them as well as the infectious theory with Chlamydia pneumoniae,
cytomegalovirus and helicobacter pylori as well as the autoreactivity hypothesis.
PMID- 9646096
TI - [Arteriosclerosis and coronary heart disease--strengths and weaknesses in the
classical risk factor concept].
AB - Several cardiovascular risk factors were identified (high LDL-cholesterol, low
HDL-cholesterol, homocystein, Lp(a), and many others). Hypercholesterolemia has
been shown to be one of the most important cardiovascular risk factors in man.
Interventional studies for primary and secondary prevention demonstrate a
beneficial effect of cholesterol lowering therapy. However, numerous CAD-patients
suffer a second coronary event despite the appropriate lipid-lowering treatment.
Furthermore moderate hypercholesterolemia has only poor predictive power
indicating an upcoming myocardial infarction. Therefore we need additional
research in CAD prevention and in identifying so far unknown or unconsidered CAD
risk factors.
PMID- 9646097
TI - [An alternative hypothesis of the pathogenesis of atherosclerosis].
AB - Why LDL entrapped in the subendothelium should trigger events leading to chronic
inflammation and to arterial wall injury is a major enigma of modern medicine.
Oxidation of LDL in vitro renders the molecule potentially atherogenic, and the
concept that oxidation is the major single event underlying the transformation of
LDL to a proinflammatory molecule dominates the world literature. Here, an
alternative hypothesis on the pathogenesis of atherosclerosis will be presented.
We have found that non-oxidative, enzymatic modification of LDL with ubiquitous
enzymes (protease + cholesterol esterase + neuraminidase) also transforms the
molecule to an atherogenic moiety. Enzymatically altered LDL (E-LDL) shares major
properties in common with lipoproteins that have been isolated from
atherosclerotic lesions. It activates complement via the alternative pathway and
is recognized by a scavenger receptor on human macrophages, thus inducing foam
cell formation. Uptake of E-LDL is accompanied by potent induction of MCP-1
synthesis and secretion. In contrast, E-LDL does not stimulate IL-1 or TNF
production and is only a weak inducer of IL-6. Monoclonal antibodies were
produced that recognize neoepitopes on E-LDL, but that do not react with native
or oxidized LDL. With the use of these antibodies, extensive deposition of E-LDL
in very early atherosclerotic lesions was demonstrated. Activated complement
components colocalized with E-LDL, corroborating the concept that
subendothelially deposited LDL is enzymatically transformed to a complement
activator at the earliest stages in lesion development. The pathogenetic
relevance of unhalted complement activation in atherogenesis was demonstrated
with the use of C6-deficient rabbits. It was found that C6-deficiency markedly
protected against development of diet-induced atherosclerosis in the experimental
animals. In sum, our hypothesis departs from the mainstream of atherosclerosis
research and derives from the recognition that extracellular exposition of free
cholesterol in LDL-particles by itself confers pro-inflammatory properties onto
the lipoprotein molecule. We believe that the degrading enzymes are ubiquitously
present in the extracellular matrix, so the only requirement for atherogenesis to
occur is the deposition of large amounts of LDL. Oxidative processes or
infections probably play only minor roles, and reduction of LDL plasma levels
will predictably represent the single most important prophylactic measure against
development and progression of atherosclerosis.
PMID- 9646098
TI - T-lymphocytes and monocytes in atherogenesis.
AB - Atherosclerosis is characterized as a chronic inflammatory-fibroproliferative
disease of the vessel wall. The attachment of monocytes and T-lymphocytes to the
injured endothelium followed by their migration into the intima is one of the
first and most crucial steps in lesion development. The co-localization of CD4+ T
cells and macrophages in the lesion, the abundant expression of HLA Class II
molecules and the co-stimulatory molecule CD40 and its ligand (CD40L) indicate a
contribution of cell-mediated immunity to atherogenesis. Transgenic mouse models
revealed that dependent on the model T- and B-cells may promote lesion
progression, monocytes and macrophages are in contrast essential for the
development of atherosclerotic lesions. Apart from the local process in the
vessel wall, systemic signs of an inflammatory reaction are also associated with
lesion development. Thus plasma levels of C-reactive protein and fibrinogen and
the white blood cell count are positively correlated to the risk of
cardiovascular disease. Recently, an inflammatory phenotype of circulating
peripheral blood monocytes could be demonstrated as a specific cellular correlate
to lipid and lipoprotein risk factors. Thus the pool size of LPS receptor
(CD14)dim and Fc gamma IIIa receptor (CD16a)+ monocytes positively correlates to
plasma cholesterol levels, to triglycerides levels and to the apolipoprotein E4
(apo E4) phenotype in contrast to a negative correlation to the high density
lipoprotein (HDL) cholesterol concentration. This CD14dim CD16a+ monocytes are
further characterized by a high expression of beta 1- and beta 2-integrins,
suggesting a higher capacity for attachment at sites of inflammation. A
proinflammatory cytokine pattern and an expansion of these cells in other
inflammatory diseases are indicating that these cells promote the inflammatory
process during atherogenesis. Surface expression of the activation antigen CD45RA
on monocytes in correlation to plasma LDL cholesterol and Lp(a) levels further
indicates an inflammatory reaction. Regarding the potential mechanisms of the
phenotypic changes of peripheral blood monocytes, in a serum free in vitro
differentiation model supplemented with M-CSF monocytes from probands which are
homozygous for apo E4 showed a significantly higher increase of CD16a expression
compared to apo E3/E3 cells indicating that a genetic polymorphism of a single
apolipoprotein gene locus may affect monocyte differentiation. The further
characterization of the cellular immunology of monocytes and T-lymphocytes in
lesion development will provide new specific diagnostic and therapeutic targets
in atherogenesis.
PMID- 9646099
TI - [Persistence of Chlamydia pneumoniae in human arteriosclerotic plaque substance.
Evidence and consequences].
AB - The obligate intracellular bacterium Chlamydia pneumoniae has recently been
implicated in the pathogenesis of atherosclerosis. Serological response to
Chlamydia pneumoniae statistically indicates an increased risk of coronary artery
disease and myocardial infarction. This surprising relation is corroborated by
the presence of chlamydial structures and even viable Chlamydia pneumoniae in
atherosclerotic plaques. These findings have already resulted in initial studies
on the potential benefit of antimicrobial therapy in coronary heart disease.
However, experimental proof of an etiological role of Chlamydia pneumoniae in
arteriosclerosis has not yet been accomplished since a well established animal
model and a system of genetic recombination are not yet available. In addition,
clinical evaluation of patients is complicated by the lack of a useful parameter
to indicate the risk of endovascular infection. Whether chlamydiae initiate
atherosclerotic injury. facilitate progression of existing plaques, or merely
colonize the lesions is therefore not known. Chlamydial contribution to the
development of atherosclerosis is a fascinating hypothesis that may initiate a
radical change of clinical practice for one of the leading causes of death. At
the current state of scientific knowledge, however, an experimental
antichlamydial treatment in coronary heart disease may only be justified in well
controlled clinical trials.
PMID- 9646100
TI - [Arteriosclerosis as a sequela of chronic Chlamydia pneumoniae infection].
AB - In the last years several new data allow a controversial but convincing
interpretation of the pathogenesis of atherosclerosis (arteriosclerosis).
Atherosclerosis can be apparently the result of ultrachronic persistent infection
by Chlamydia pneumoniae and not the result of different risk factors. The main
arguments for the chlamydial genesis are: 1. Correlation of coronary heart
disease and other atherosclerotic disease with antibodies against C. pneumoniae.
2. C. pneumoniae could be detected with different techniques (PCR,
immunohistology, electromicroscopy, culture) in a high percentage in atheromas
from different sites. 3. Three international studies with macrolides in coronary
heart disease were successful. 4. The target cells of atherosclerosis
(endothelia, macrophages, muscle cells) can be infected by C. pneumoniae in
vitro. 5. Positive animal experiments. The Koch-Henle criteria for the proof of
the etiology are largely fulfilled--even if there are doubts about the validity
of these criteria in chronic local infections. A number of unexplainable aspect
of atherosclerosis can be seen in a new light. The higher incidence of coronary
heart disease in young males has a parallel in the remarkable androtropism of
many bacterial diseases (pneumococcal pneumonia, tuberculosis). The reduction of
incidence of atherosclerotic diseases since 1965 can be explained by the much
higher intake of doxycyclin and macrolides. The low incidence of coronary heart
disease in France--sometimes regarded as an effect of red wine--can be explained
as a result of a much higher use of antichlamydial antibiotics. The increase of
inflammatory parameters (C-reactive protein, fibrinogen, leucocytes) before acute
coronary infarction are not risk factors but signs of an active chronic
infection. The interpretation is possible, that atherogenic changes in lipids
like increase of LDL and decrease of HDL are not risk factors but consequence of
chronic arterial infection by chlamydia. The low incidence of atherosclerosis in
the tropics--despite high frequency of chlamydial infection--is difficult to
explain. Vascular infection can be related with the age of the patient at the
primary infection. With low hygiene, intestinal primary infections in early
childhood can be possible. Arterial infection would be thus a result of a primary
infection in adolescence ("yet another poliomyelitis story"). There are good
arguments for the thesis that C. pneumoniae is the primary cause of
atherosclerosis and not a secondary invader. The consequence, nevertheless, is
similar: Antibiotics get a key role. The macrolides roxithromycin, azithromycin,
clarithromycin and the tetracyclin doxycyclin fulfill the criteria as potential
antichlamydial agents. In general a longer treatment (6 to 8 to 12 weeks) seems
advisable. It is necessary to start international studies with antibiotics in
coronary infarction and other clinical manifestations of atherosclerosis. The
relevant antibiotics licensed for chlamydial infections are cheap and safe.
Despite of the urgent need for controlled studies, it seems already justified to
treat high-risk patients with antibiotics. Meticulous protocols and long-term
control of patients are necessary to evaluate the therapeutic effects. Preventive
studies in patients without clinical manifestation of atherosclerosis are
urgently needed. The risks of resistance or side effects are neglectable, but the
organisation of such studies would be very difficult.
PMID- 9646101
TI - [Cytomegalovirus and herpes simplex virus in pathogenesis and progression of
native arteriosclerosis and recurrent stenosis after intervention].
AB - An increasing number of clinical and experimental studies point to a contribution
of various infectious organisms like chlamydia pneumoniae or herpesviruses to
atherosclerosis in man. Cytomegalovirus induces atherosclerotic lesions in
animals. In vitro studies reveal functional changes of endothelial cells after
infection with cytomegalovirus. Infection with this virus renders endothelial
cells immunogenic for cellular and humoral immune reactions. In man a significant
association of infections with herpesviruses and atherosclerosis could be
established in several studies. Cytomegalovirus infection has been incriminated
as an independent risk factor in restenosis after coronary angioplasty.
PMID- 9646102
TI - Transplant vasculopathy.
AB - Transplant vasculopathy constitutes the major impediment to long-term survival in
heart transplant recipients. Within the "response to immune injury" paradigm, it
can best be understood as the resultant of an orchestrated recipient immune
response to the initial allogenic stimulus by graft vascular endothelium. This
response incorporates the elaboration of complex coordinated cytokine patterns
and corresponding cell types including B-lymphocytes, T-helper1- and T-helper2
cells, cytotoxic T-cells, macrophages, and polymorphonuclear cells. These attack
the alloantigenic vascular endothelium and lead, by complex cytokine signaling,
to migration of donor smooth muscle cells from the media into the intima,
associated with a switch from the contractile to a synthetic phenotype. In
conjunction with recipient T-cells, macrophages, and lipids, the intimal
fibroproliferative growth of the donor vessel is hereby initiated.
PMID- 9646103
TI - Acute parvovirus B19 infection in pregnant women--an analysis of serial samples
by serological and semi-quantitative PCR techniques.
AB - The serological and virological course of parvovirus B19 infection was followed
in 14 women who suffered symptomatic or subclinical acute infection during
pregnancy. Serial serum samples from the patients were tested for IgG and IgM
antibodies and the levels of parvovirus B19 DNA were monitored using a semi
quantitative PCR assay. In addition, the outcome of the pregnancies was
documented by clinical information and by testing cord blood for parvovirus B19
specific antibodies as well as for parvovirus B19 DNA by PCR. Levels of IgG
antibodies rose steadily within 2 months of infection and in some cases began to
decline at the end of pregnancy. IgM antibodies were usually detected for at
least 2 months and persisted for as long as 9 months in one case. Viral DNA was
detectable for at least 8 weeks following infection and semi-quantitative
analysis revealed a gradual reduction in virus load during the viraemic phase of
infection. There were no apparent differences in the course of antibody
development and duration of viraemia in symptomatic versus subclinical
infections.
PMID- 9646104
TI - In vitro conversion of Borrelia burgdorferi to cystic forms in spinal fluid, and
transformation to mobile spirochetes by incubation in BSK-H medium.
AB - The purpose of this study was to examine the structural alterations of Borrelia
burgdorferi when exposed to spinal fluid. Normal, mobile spirochetes were
inoculated into spinal fluid, and the spirochetes were converted to cysts
(spheroplast L-forms) after 1-24 h. When these cystic forms were transferred to a
rich BSK-H medium, the cysts were converted back to normal, mobile spirochetes
after incubation for 9 to 17 days. The cultures were examined by dark field
microscopy (DFM), interference contrast microscopy (ICM) and transmission
electron microscopy (TEM). When neuroborreliosis is suspected, it is necessary to
realize that B. burgdorferi can be present in a cystic form, and these cysts have
to be recognized by microscopy. This study may also explain why cultivation of
spinal fluid often is negative with respect to B. burgdorferi.
PMID- 9646105
TI - Antibody testing and RT-PCR results in hepatitis C virus (HCV) infection: HCV-RNA
detection in PBMC of plasma viremia-negative HCV-seropositive persons.
AB - To evaluate the concordance between viremia and antibody testing in hepatitis C
virus (HCV) diagnosis, 682 serum or plasma samples collected from patients with
known or suspected HCV infection were tested. An overall concordance of 77%
between serological and PCR results was found, 5% was RNA positive/antibody
negative and 18% antibody positive/RNA negative. The relationship between HCV
infection, risk group and clinical diagnosis was studied in 116 patients: the
presence of anti-HCV antibody without viremia was shown in 72.7% of asymptomatic
subjects and 17.6% of chronic hepatitis subjects without interferon treatment.
However, the detection of HCV-RNA in peripheral blood mononuclear cells (PBMC) in
four out of 38 plasma viremia-negative HCV-seropositive subjects (10.5%), showed
that HCV-RNA could persist in PBMC and could begin the viral replication again at
different times. The detection of HCV-RNA in PBMC in anti-HCV-positive subjects
without viremia could reduce false-negative results of HCV-RNA testing by RT-PCR
in serum or plasma.
PMID- 9646106
TI - Gram-negative bacteremia in non-neutropenic patients: a 3-year review.
AB - The causative organisms, clinical manifestations, factors influencing prognosis,
and other epidemiological characteristics of 81 episodes of bacteremia due to
gram-negative organisms, in non-neutropenic patients, were studied
retrospectively during a 3-year period (1992-1994) at the Department of Internal
Medicine of the University Hospital of Heraklion, Crete, Greece. The gram
negative bacteremia incidence was 2% and the overall mortality 12%. All 81
patients had fever; Escherichia coli was the most frequent organism isolated
(from 47 patients--58%) and was associated with shock (9/47), disseminated
intravascular coagulation (DIC) (8/47), anuria (5/47), adult respiratory distress
syndrome (ARDS) (3/47), and pneumonia (1/47). Other less frequent gram-negative
microorganisms were Klebsiella spp. (ten patients; 12%), Pseudomonas spp. (7;
7%), Salmonella spp. (5; 6%), Enterobacter spp. (5; 6%), Proteus spp. (3; 3.4%),
Stenotrophomonas spp. (3; 3.4%), and Acinetobacter spp. (1; 1.2%). ARDS. shock,
DIC, anuria, presence of central venous catheter, urinary catheter, unknown
origin of infection and inappropriate treatment were significantly associated
with a higher death rate. Early initiation of appropriate therapy was the most
important intervention that favorably affected the outcome of gram-negative
bacteremias in this patient population.
PMID- 9646108
TI - Intracellular activity of vancomycin and Ly333328, a new semisynthetic
glycopeptide, against methicillin-resistant Staphylococcus aureus.
AB - The activity of vancomycin and Ly333328, a new semisynthetic glycopeptide,
against eight strains of Staphylococcus aureus showing various susceptibilities
to methicillin and ciprofloxacin was examined using a colony count method. We
compared the growth of strains ingested by polymorphonuclear leucocytes and non
ingested strains. MICs of vancomycin and Ly333328 against staphylococci resistant
and susceptible to methicillin were 2 mg/l and 2-4 mg/l, respectively. Against
all the tested extracellular staphylococci, vancomycin had only bacteriostatic
activity, whereas Ly333328 showed cidal activity at 10 MIC. Against ingested
staphylococci, vancomycin had nearly no activity compared with the controls,
regardless of the concentration of the drug. Ly333328 at concentrations of 1 MIC
and above was highly active against ingested staphylococci regardless of their
susceptibility pattern. The results suggest that Ly333328 in contrast to
vancomycin is active against intracellular S. aureus.
PMID- 9646107
TI - Concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi
sensu lato in patients with acute meningitis or meningoencephalitis.
AB - From September 1992 to August 1993, 338 patients over the age of 15 years
presented to the Department of Infectious Diseases, University Medical Centre
Ljubljana, with acute lymphocytic meningitis. In 89 of these patients (26.3%)
serum IgM and IgG antibodies against tick-borne encephalitis (TBE) virus were
detected, and in 59 patients (17.5%) a borrelial etiology of disease was
demonstrated by one or more of the following presence of intrathecal antibody
production, seroconversion to borrelial antigens, presence of erythema migrans,
and/or isolation of Borrelia burgdorferi sensu lato from skin or cerebrospinal
fluid. Of the 148 patients who fulfilled criteria for TBE or borrelial infection,
concomitant infection with TBE virus and B. burgdorferi sensu lato was
demonstrated in 12 patients (3.6% of all patients presenting with acute
lymphocytic meningitis). In the majority of patients with concomitant infection
the clinical features at presentation were characteristic of, or consistent with,
TBE. In addition, during follow-up studies, eight of the 12 patients subsequently
developed signs and symptoms compatible with minor and/or major manifestations of
Lyme borreliosis. Six patients were diagnoses with neuroborreliosis based on
signs or symptoms and/or laboratory tests. These findings show that in patients
with acute lymphocytic meningitis or meningoencephalitis, originating in TBE and
Lyme borreliosis endemic regions, the possibility of concomitant infection should
be considered.
PMID- 9646109
TI - Serum procalcitonin rise is only slight in two cases of disseminated
aspergillosis.
AB - High serum concentrations of procalcitonin (PCT) have been found during bacterial
and parasitic infections. This is a report of two cases of disseminated
aspergillosis with moderate PCT increase in two 14-year-old girls after bone
marrow transplantation (BMT) for myelodysplastic syndrome and Fanconi's anemia,
respectively. In contrast, the important rise of serum CRP observed in these
patients tends to demonstrate that the synthesis of these two proteins is under
different control mechanisms.
PMID- 9646110
TI - Investigation of Rickettsia conorii antibodies in the Antalya area.
AB - Mediterranean spotted fever, caused by Rickettsia conorii, is a tick-borne
infection. Serum samples for screening R. conorii antibodies of professionally
exposed persons in the Antalya region, on the Mediterranean coast of Turkey, were
analyzed. R. conorii IgG antibodies were detected in 13 of 98 (13.3%) serum
samples. Mediterranean spotted fever antibodies were found to be positive in 9.4%
of the men and 15.2% of the women (a total of 13 cases). Only three cases had a
history of fever and rash.
PMID- 9646111
TI - HCV genotypes in patients with chronic hepatitis C in Croatia.
AB - The determination of hepatitis C virus (HCV) genotype is an important
epidemiological parameter in patients with chronic hepatitis C, while its
clinical significance is still a matter of debate. The HCV genotypes in a group
of 203 Croatian patients with chronic hepatitis C were examined. Genotypes were
correlated to different risk factors, age, duration of the disease, liver
histology activity and level of viremia. HCV-RNA was detected in each serum by
means of reverse transcription PCR. Genotypes were determined from the
amplificate by reverse hybridization in a line probe assay. The level of viremia
was assessed by branched DNA (bDNA) signal amplification. The most common
genotype was 1b (61.1% of patients), followed by 3a (26.1%), and 1a (10.8%).
Other genotypes such as 2a and 4 were only rarely found in our patients (2%).
Genotype 1b was most commonly acquired via blood transfusion, while genotype 3a
was strongly related to intravenous drug use. Genotype 1b was associated with
older age (mean 42.6 vs 29.3 years), longer duration of the disease (mean 6.0 vs
3.5 years), higher histologic activity score (mean 13.2 vs 10.6) and higher
viremia (mean 9.06 vs 5.93 Meq/ml) at statistically significant levels (p <
0.001) when compared to genotype 3a. The prevalence of HCV genotypes follows the
patterns of southeastern European countries, except for a lower prevalence of
genotype 2. The observation that genotype 1b is associated with higher viremia
and more severe liver injury is confirmed.
PMID- 9646112
TI - Whipple's disease with aortic regurgitation requiring aortic valve replacement.
AB - Cardiac involvement in Whipple's disease is well established. However, clinical
consequences beside antibiotic therapy have rarely been reported. Our observation
of a middle-aged man with increasing dyspnea, fatigue, chest pain, and dizziness
leading to admission to a cardiology department demonstrates that cardiac
symptoms may represent the main symptoms in patients with Whipple's disease. The
diagnosis was not made prior to upper endoscopy, performed because of diarrhea,
and revealed Whipple's agent now classified as Tropheryma whippelii, which is a
PAS-positive rod-shaped bacterium in the macrophages of the intestinal lamina
propria. The aortic valve was replaced after the intestinal symptoms were
resolved by antibiotic treatment reducing the number of infectious agents in the
duodenal mucosa. Histological analysis of the aortic valve demonstrated the
presence of PAS-positive rod shaped material as the most likely cause of aortic
insufficiency. Five months after valve replacement, the patient had completely
recovered from intestinal and cardiac symptoms. Still under antibiotic treatment
16 months later, no more PAS-positive macrophages were detectable in the
intestinal mucosa.
PMID- 9646113
TI - Cerebral Dermabacter hominis abscess.
AB - Dermabacter species are commonly isolated from the skin and other body sites but
rarely show pathogenicity in humans. A case of Dermabacter hominis cerebral
abscess is reported which presented as a contrast-enhancing intracranial mass in
a renal transplant patient.
PMID- 9646115
TI - Extended spectrum beta-lactamase reactions in Stenotrophomonas maltophilia.
PMID- 9646114
TI - Disseminated infection with Saccharomyces kluyveri in a patient with AIDS.
AB - A 47-year-old man with acquired immune deficiency syndrome was found to have
disseminated Saccharomyces kluyveri infection. The yeast was isolated from blood
and cerebro-spinal fluid. An autopsy revealed the presence of the microorganism
in many organs including liver, kidneys, pancreas, spleen, lung, and brain. The
case confirms a potential pathogenicity of yeasts of the genus Saccharomyces in
patients with profound immune deficiency, especially in advanced HIV infection.
PMID- 9646116
TI - Patterns and outcome of septicemia in neutropenic children with cancer in a Greek
hospital.
PMID- 9646117
TI - Secondary vulvar and pulmonary mucormycosis in a trauma patient.
PMID- 9646118
TI - Chronic myelogenous leukemia in an HIV-infected patient.
PMID- 9646119
TI - Spondylodiscitis by Candida albicans.
PMID- 9646120
TI - A case of human rabies in The Netherlands.
PMID- 9646121
TI - Prurigo nodularis in HIV-infected individuals.
PMID- 9646122
TI - Adverse drug reactions of the new oral antifungal agents--terbinafine,
fluconazole, and itraconazole.
PMID- 9646123
TI - Inflammatory perifollicular fibrosis and alopecia.
PMID- 9646124
TI - Desideratum dermatologica--wanted: an extensive menu of patch test allergens
available to American dermatologists.
PMID- 9646125
TI - The significance of Demodex folliculorum density in rosacea.
AB - BACKGROUND: Demodex folliculorum has been reported in rosacea in a number of
clinical studies. As the Demodex mite is also present in many healthy
individuals, it has been suggested that the mite may have a pathogenic role only
when it is present in high densities. Moreover, some authors have proposed that a
mite density above 5/cm2 may be a criterion for the diagnosis of inflammatory
rosacea. In this study, the possible role of D. folliculorum and the importance
of mite density in rosacea were investigated using a skin surface biopsy
technique. METHODS: Thirty-eight patients with rosacea and 38 age-and-sex-matched
healthy subjects entered the study. With the skin surface biopsy technique, we
obtained samples from three facial sites. We then determined the mite
positivities, the mean mite counts in both study groups, the mean mite densities
at each facial site and in the rosacea subgroups, and the mite densities above
5/cm2. RESULTS: The mean mite count in the rosacea group (6,684) was
significantly higher than that in controls (2,868; p < 0.05). The cheek was the
most frequently and heavily infested facial region. Ten rosacea patients and five
normal subjects had mite densities over 5/cm2; the difference was not
statistically significant (p > 0.05). CONCLUSIONS: Rosacea is a disease of
multifactorial origin, and individual properties may modify the severity of the
inflammatory response to Demodex. We suggest that a certain mite density is not
an appropriate criterion in the diagnosis of the disease; nevertheless, large
numbers of D. folliculorum may have an important role in the pathogenesis of
rosacea, together with other triggering factors.
PMID- 9646126
TI - Aerobic and anaerobic microbiology of chronic venous ulcers.
AB - BACKGROUND: The role of bacteria in the pathogenesis of chronic venous leg ulcers
(CVLU) is unclear. The objective of the study was to establish the aerobic and
anaerobic bacteriology of CVLU. METHODS: A retrospective review was carried out
of the clinical and microbiological laboratory records obtained from patients
with CVLU. Microorganisms were grown from 43 specimens obtained from 41 patients.
RESULTS: Aerobic or facultative bacteria alone were present in 18 (42%)
specimens, anaerobic bacteria only in three (7%), and mixed aerobic-anaerobic
flora in 22 (51%). In total, there were 97 isolates, 64 aerobic or facultative
and 33 anaerobic, an average of 2.3 isolates per specimen (1.5 aerobes and 0.8
anaerobes). The predominant aerobic organisms were Staphylococcus aureus (26
isolates), group D streptococci (5), and Escherichia coli(5). The predominant
anaerobes were Peptostreptococcus spp. (15), Bacteroides fragilis group (6),
Propionibacterium acnes (4), and Prevotella spp. (3). CONCLUSIONS: CVLU have a
polymicrobial aerobic-anaerobic flora.
PMID- 9646127
TI - Physiologic skin changes during pregnancy: a study of 140 cases.
AB - BACKGROUND: The endocrine, metabolic, and immunologic changes during pregnancy
give rise to a number of physiologic cutaneous changes. OBJECTIVE: We evaluated
140 pregnant women to determine the pattern of pregnancy-induced physiologic skin
changes in our community. RESULTS: The various changes observed include:
increased pigmentation (90.7%), striae (77.1%), edema (48.5), melasma (46.4%),
vascular changes (34.2%), and others. CONCLUSIONS: Pigmentary changes were the
most common finding, whereas the incidence of vascular changes was quite low (p <
0.01).
PMID- 9646128
TI - Eosinophilic ulcer of oral mucosa.
PMID- 9646129
TI - Cutaneous polyarteritis nodosa: a report of a case associated with melioidosis
(Burkholderia pseudomallei).
PMID- 9646130
TI - Eruption of human immunodeficiency virus seroconversion.
PMID- 9646131
TI - Cutaneous Paecilomyces lilacunis infection in a hospitalized patient taking
corticosteroids.
PMID- 9646132
TI - Human gnathostomiasis in Mexico.
PMID- 9646133
TI - Lymphoscintigraphy in yellow nail syndrome.
PMID- 9646134
TI - Short treatment schedules of itraconazole in dermatophytosis.
PMID- 9646135
TI - Topical hydroquinone in the treatment of some hyperpigmentary disorders.
PMID- 9646136
TI - Butenafine, a fungicidal benzylamine derivative, used once daily for the
treatment of interdigital tinea pedis.
PMID- 9646137
TI - Oral treatment schedules for onychomycosis: a study of patient preference.
AB - BACKGROUND: An improved understanding of patients' attitudes to medication may
help promote compliance with oral medications for onychomycosis. This study was
performed to assess patients' preference between continuous and intermittent oral
treatment schedules for onychomycosis and to determine the reasons underlying the
selections made. METHODS: Patients were eligible for inclusion if they had
current onychomycosis and were willing to take oral medication for this
condition. In a 30-min, face-to-face interview, each patient answered questions
about four possible treatment schedules for onychomycosis; regimen 1--continuous
(daily regular intake) for 12 weeks; regimen 2--intermittent 1 week/month for 3
months (last week of therapy is week 9); regimen 3--intermittent once weekly for
21 weeks; regimen 4--intermittent 1 week/month for 4 months (last week of therapy
is week 13). RESULTS: A total of 102 patients from Germany and Spain participated
in the study. When asked to choose between regimens 1, 2, and 3, 46% of patients
favored the 9-week intermittent schedule, 42% selected the 12-week continuous
schedule, and 12% preferred the 21-week intermittent schedule. The preference for
the 9-week intermittent schedule was more notable among younger patients (< 45
years), possibly because they are less used to taking regular medication, and
among Spanish patients, an effect that could not be attributed to age because the
average age of patients was similar in the participating countries (Germany 47.2
years; Spain 48.0 years). When the patients who preferred regimen 2 were asked to
choose between regimens 1, 3, and 4 (both intermittent schedules longer than the
continuous schedule), most (57%) favored the shortest treatment schedule (regimen
2). CONCLUSIONS: Overall, patients favored an intermittent schedule lasting 9
weeks. Treatment duration is the critical factor in determining patients'
preference for treatment schedules for onychomycosis.
PMID- 9646138
TI - A questionnaire study on the management of onychomycosis: a Canadian perspective.
AB - BACKGROUND: Onychomycosis of the toenails is a condition that responds poorly to
griseofulvin. The introduction of terbinafine in Canada in May 1993 resulted in a
marked shift in the choice of treatment for pedal onychomycosis. METHODS: A
questionnaire survey was carried out in 1996 among Canadian dermatologists
regarding the management of onychomycosis. RESULTS: There were 160 respondents
from the roughly 350 practicing dermatologists. The dermatologists saw 8 +/- 0.6
patients per week (average +/- standard error (SE) with suspected or diagnosed
onychomycosis, with 5 +/- 0.5 patients per week consulting the dermatologists for
the first time. Most dermatologists performed mycological testing prior to
starting treatment for onychomycosis. The management options for onychomycosis
(mean +/- SE) were oral systemic antifungal therapy 51 +/- 3%, no therapy 31 +/-
3%, and nondrug therapy 9 +/- 2%. The majority of dermatologists (83%) used
terbinafine as first-line therapy if, indeed, they used oral antifungal agents.
In contrast, griseofulvin and ketoconazole were used as first-line therapy in 5%
and 1% of cases, respectively. In Canada, there are no monitoring requirements
when using oral terbinafine for onychomycosis. Therefore, it is not surprising
that only 30% of dermatologists performed monitoring with terbinafine. In
contrast, the frequency of monitoring with griseofulvin and ketoconazole was 40%
and 80%, respectively. The subset of dermatologists who reported monitoring
carried it out in only a fraction of their patients: 47%, 53% and 83% for
terbinafine, griseofulvin, and ketoconazole, respectively. Therefore, the overall
number of patients in whom regular monitoring was performed was 14.1% 21.2%, and
71.4% for terbinafine, griseofulvin, and ketoconazole, respectively. The
perceived cure rates with terbinafine and griseofulvin (mean +/- SE) were 83.7 +/
1% and 41 +/- 3.1%, respectively. CONCLUSIONS: In May 1996, within three years
of the introduction of terbinafine to Canada, this agent has become the drug of
choice for the treatment of pedal onychomycosis (at the time of the survey
neither itraconazole or fluconazole were approved for onychomycosis). Terbinafine
has been found to be very effective and safe, and only a minority of
dermatologists perform regular monitoring with this drug.
PMID- 9646139
TI - A pilot study on bacterial viability in acne. Assessment using dual flow
cytometry on microbials present in follicular casts and comedones.
AB - BACKGROUND: Antibiotic therapy is one of the main methods of acne treatment,
however, bacterial resistance is on the rise and can affect the treatment
outcome. Quantitative bacteriologic cultures are the gold standard methodology
for the assessment of such a problem; however, certain important biological
aspects remain uncovered. OBJECTIVE: The purpose of this study was to compare the
antibacterial activity of minocycline and lymecycline in sebaceous follicle
infundibula and comedones of acne patients. METHOD: We used a recently introduced
flow cytometric method, allowing a distinction to be made between viable, injured
(presumably resistant), and dead microorganisms. RESULTS: Minocycline (100 mg)
proved to be superior to lymecycline (600 mg) in abating the microflora harboring
in the sebaceous follicles of acne patients. CONCLUSIONS: The dissimilar
bioavailability and antimicrobial efficacy between the two bacteriostatic agents
may impart different clinical efficacy.
PMID- 9646140
TI - Jaipur block in postherpetic neuralgia.
AB - BACKGROUND: Postherpetic neuralgia, a common sequele to herpes zoster infection,
is a chronic debilitating problem. The available therapeutic modalities are
usually ineffective. METHODS: A total of 3960 patients (1326 women and 2634 men;
age group, 21-84 years), with postherpetic neuralgia as the presenting complaint
and with pain lasting from 2 months to 5 years, were treated with Jaipur block,
consisting of local subcutaneous infiltration of 2% xylocaine, 0.5% bupivacaine,
and 4 mg/mL dexamethasone solution. Patients were followed up at six-weekly
intervals with subsequent injections given in non-responders. RESULTS: Twenty
eight per cent of patients obtained complete relief from pain after a single
injection, another 57% after a second injection, and 11% after a third injection;
4% of patients did not respond to treatment. The non-responders were either old
(over 60 years) or had pain lasting for more than 2 years. The response to
therapy was similar in both sexes. There were 31 left-handed patients in this
study. Pain was less severe in left-handed patients and they obtained complete
relief after a single injection. Side-effects including giddiness and sweating
were seen, occasionally, in a few patients. CONCLUSIONS: Ninety six per cent of
patients obtained complete relief after the block with a follow-up of up to 19
years.
PMID- 9646141
TI - Henri Feulard (1858-1897): the life and works of the secretary of the First
International Congress of Dermatology.
PMID- 9646142
TI - Familial occurrence of coexistence of bullous pemphigoid and Sjogren's syndrome.
PMID- 9646143
TI - Zosteriform skin metastases from breast carcinoma in association with herpes
zoster.
PMID- 9646144
TI - Why is there no cobblestoning in lichen sclerosus et atrophicus treated by punch
grafting?
PMID- 9646145
TI - Acneform eruption with iodized salt.
PMID- 9646146
TI - Neurosis and personality disorder in old age. Klaus Bergmann. In Studies in
Geriatric Psychiatry Eds A. D. Isaacs and F. Post (1978). John Wiley, Chichester,
pp. 41-75.
PMID- 9646147
TI - Alcohol related dementia: proposed clinical criteria.
AB - Current diagnostic criteria for Alcohol Related Dementia (ARD) are based almost
exclusively on clinical judgment. Moreover, there are no guidelines available to
assist the clinician or the researcher in distinguishing Alcohol Related Dementia
from other causes of dementia such as Alzheimer's Disease (AD). However, this
distinction may have implications for the prognosis and treatment of patients. In
this article, provisional diagnostic criteria for establishing a diagnosis of
Alcohol Related Dementia are proposed for further study. The criteria are based
on the available literature on the relationship between alcohol consumption and
dementia and were modeled after existing diagnostic criteria for AD and Vascular
Dementia. Validity of these criteria for distinguishing AD from ARD will require
further study.
PMID- 9646148
TI - Religious attitudes and practices of hospitalized medically ill older adults.
AB - OBJECTIVES: To examine the prevalence of religious beliefs and practices among
medically ill hospitalized older adults and relate them to social, psychological
and health characteristics. METHODS AND PROCEDURES: Consecutive patients age 60
or over admitted to the general medicine cardiology and neurology services of
Duke University Medical Center were evaluated for participation in a depression
study. As part of the evaluation, information on religious affiliation, religious
attendance, private religious activities, intrinsic religiosity and religious
coping was collected. Demographic, social, psychological and physical health
characteristics were also assessed. Bivariate and multivariate correlates of
religious belief and activity were examined using Pearson correlation and linear
regression. RESULTS: Of the 542 patients evaluated, detailed information on
religious beliefs and behaviors was collected on 455 cognitively unimpaired
patients. Over one-half (53.4%) of the sample reported attending religious
services once per week or more often; 58.7% prayed or studied the Bible daily or
more often; over 85% of patients held intrinsic religious attitudes; and over 40%
spontaneously reported that their religious faith was the most important factor
that enabled them to cope. Religious variables were consistently and
independently related to race (Black), lower education, higher social support and
greater life stressors, and religious attendance was associated with less medical
illness burden. Religious attendance was also related to lower depressive
symptoms, although the association weakened when other covariates were
controlled. CONCLUSIONS: Religious practices, attitudes and coping behaviors are
prevalent among hospitalized medically ill older adults and are related to
social, psychological and physical health outcomes. Implications for clinical
practice are discussed.
PMID- 9646149
TI - The Taps Project 40: quality of care provisions for the elderly mentally ill-
traditional vs alternative facilities.
AB - The study evaluates some aspects of care reprovision for psychogeriatric
patients. Seven hospital wards are compared with four community settings,
established as part of the reprovision programme for Friern Hospital in London.
Each facility was assessed for policy and programme, social climate and physical
characteristics; staff attitudes in regard to their tasks, training needs and job
satisfaction were also explored. Community settings were superior to hospital
wards in providing more privacy for the residents and were better equipped with
physical amenities and safety features. There were relatively small differences
between the way staff perceived the social climate in community homes and in
hospital. The former were regarded as encouraging greater independence. Care
staff in the hospital were more likely to express dissatisfaction with pay,
working conditions and social status, while community staff were more
dissatisfied with the quality of cooperation between staff members. Clients
transferred to Social Services facilities had a higher level of functioning and
needed less on-site medical care. This was further reflected by the lower
frequency of nursing care tasks being performed by staff in community facilities.
Overall, the shift towards a less medical model of care in community-based homes
appears to be beneficial to psychogeriatric patients, provided that current and
prospective physical needs of the residents are adequately addressed.
PMID- 9646150
TI - Total serum homocysteine in senile dementia of Alzheimer type.
AB - OBJECTIVE: The main hypothesis was that subtle vitamin B12 deficiencies occur
more commonly in senile dementia of Alzheimer type (SDAT) that in healthy elderly
individuals, and may be revealed by elevated total serum homocysteine (tHcy). A
subsidiary hypothesis was that such deficiencies would be nutritionally
independent as determined by retinol binding protein (RBP). DESIGN: A prospective
case-controlled survey. SETTING: A Welsh urban psychogeriatric assessment centre
and local general practice. PATIENTS: Thirty patients, aged 65 or over, seen
consecutively in 1994 with features compatible with DSM-III-R criteria for
primary degenerative dementia of Alzheimer type and 30 cognitively intact age
matched control subjects. MEASURES: Diagnosis was assessed using the CAMDEX.
Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE
scores for control subjects. THcy was measured using high performance liquid
chromatography (HPLC), and RBP assayed by a radial immunodiffusion method.
RESULTS: Patients had a highly significant elevation of tHcy compared with
control (p < 0.0001). Multiple regression highlighted the interrelated effects of
tHcy and total serum cobalamin on cognitive scores. RBP did not differ between
groups. Macrocytosis was absent, and neutrophil hypersegmentation uncommon, in
hyperhomocysteinaemic patients. CONCLUSIONS: SDAT patients have significantly
elevated tHcy. This is independent of RBP determined nutritional status.
'Classical' haematological changes of cobalamin or folate deficiency are poor
predictors of tHcy in these patients. Aberrant cobalamin tissue delivery appears
to contribute to SDAT cognitive decline. Relative contributions of other tHcy
determinants require further investigation.
PMID- 9646151
TI - Can depression and depressive symptoms predict mortality at 18-month follow-up in
acutely medically ill inpatients over the age of 80 years?
AB - BACKGROUND: The prevalence of depression in acutely medically ill elderly
inpatients is high. Depression in the elderly is associated with increased
mortality. METHOD: The association between mortality at 18-month follow-up and
depression, depressive symptoms and demographic variables at the outset in a
cohort of acutely medically ill elderly inpatients was examined. RESULTS: The
mortality at 18-month follow-up was 47%. Depression, depressive symptoms and
demographic variables were not associated with mortality. CONCLUSION: An
important explanation of this absence of association between mortality and
depression may be an artifact due to patient selection designed to resemble
normal clinical practice.
PMID- 9646152
TI - Scopolamine-induced cognitive impairment as a predictor of cognitive decline in
healthy elderly volunteers: a 6-year follow-up.
AB - OBJECTIVE: To determine if scopolamine-induced cognitive impairment in healthy
elderly people predicts cognitive decline 6 years later. DESIGN: Prospective
cohort study. SETTING: Elderly care research unit. PARTICIPANTS: Healthy elderly
people who were part of a volunteer panel of research subjects. INTERVENTIONS:
Scopolamine 0.2 mg administered subcutaneously at baseline. MAIN OUTCOME
MEASURES: Cognitive drug research computerized cognitive testing battery pre- and
post-scopolamine, with repeat testing over 6 years later. MAIN RESULTS: 16/24
subjects were retested. Although marked decrements in cognitive functioning were
seen with scopolamine, there was little change in performance over 6 years, and
no significant association was seen between scopolamine-induced decrement and
change over time. CONCLUSIONS: The scopolamine challenge test is not likely to
play a role in the preclinical diagnosis of Alzheimer's disease.
PMID- 9646153
TI - Determinants of carer stress in Alzheimer's disease.
AB - OBJECTIVES: To explore the impact of subgroups and individual symptoms of non
cognitive disturbance on the carers of Alzheimer's disease patients. DESIGN:
Cross-sectional study using clinically valid scales to assess patient
symptomatology and self-report questionnaires to measure carer variables.
SETTING: Old age psychiatry outreach services in South and Central Manchester.
SUBJECTS: 100 patients with Alzheimer's disease living at home and their carers.
MAIN OUTCOME MEASURES: Subjective burden and distress in carers. RESULTS:
Separate statistical analyses were performed for subgroups and individual
symptoms of non-cognitive disturbance. For subgroups, multivariate analyses
identified depression and behavioural disturbances in patients as significant
predictors of subjective burden in carers. Carer distress was predicted by
depression, psychosis and cognitive impairments in patients and carer gender. For
individual symptoms of non-cognitive disturbance, three features of depression in
patients (mood-related signs, physical signs and behaviour changes), walking
disruptions and the patient-carer relationship predicted of subjective burden in
carers. Variance in the level of carer distress was accounted for by sleep
disruptions, hallucinations and mood-related depressive features in patients and
carer gender. CONCLUSION: The findings confirm that the non-cognitive features of
Alzheimer's disease are stressful for carers and indicate specific relationships
between mood-related and behavioural signs of depression, walking and sleep
disruptions and hallucinations in patients and adverse carer outcomes. Patient
depression and the mood-related signs of depression in particular were the most
consistent and powerful predictors of psychological morbidity in carers.
Intervention strategies need to identify and target troublesome behaviours in
patients and aim to either change these behaviours or alter the way carers
respond to them. Thus, interventions need to be symptoms-rather than service-led
and are likely to require multidisciplinary and multi-agency approaches.
PMID- 9646154
TI - Rating depression severity in the elderly physically ill patient: reliability and
factor structure of the Hamilton and the Montgomery-Asberg Depression Rating
Scales.
AB - OBJECTIVES: To assess the appropriateness of the Hamilton Depression Rating Scale
and the Montgomery-Asberg Depression Rating Scale in depressed elderly physically
ill patients. DESIGN: Depression scale scores from depressed medical inpatients
were assessed for internal consistency using Cronbach's alpha, and subjected to
exploratory principal components factor analyses. SUBJECTS: 100 medical
inpatients, aged 65 years and over (median age 80.5 years, range 66-99), 74
female, with Geriatric Mental State Schedule-AGECAT case level diagnoses of
depression. MATERIALS: The 17-item Hamilton Depression Rating Scale (HDS) and the
Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Coefficient alpha for
the HDS was 0.46; for the MADRS 0.61. Successive deletion of HDS items to
maximize alpha resulted in a six-item scale (alpha = 0.60); after deletion of
five MADRS items, alpha was 0.77. Factor analysis of the HDS yielded a four
factor solution accounting for 57% of the variance, the majority due to anxiety
and insomnia items; the MADRS yielded a two-factor solution explaining 60% of the
variance. CONCLUSIONS: Coefficient alpha for both scales is well below the
minimum necessary for the total score to be used to represent a single construct.
The HDS appears to be an unreliable measure of depression severity in elderly
people with physical illness, as the major variance in the scores is due to
anxiety and insomnia. The MADRS performs better, and with modification may be an
appropriate measurement of depression severity in this population.
PMID- 9646155
TI - Late onset of schizophrenia and temporal lobe epilepsy: coincidence or causal?
PMID- 9646156
TI - The time-related expression of p53 protein in human skin wounds--a quantitative
immunohistochemical analysis.
AB - The time-dependent expression of p53 protein during wound healing has been
investigated by immunochemistry in fibroblastic cells of skin wounds ranging
between a few minutes and 11 weeks old. When compared to uninjured skin, an
increased expression of p53 was found earliest in a wound with a postinfliction
interval of 3 days. The ratio (r) of positively stained cells in relation to the
total number of fibroblastic cells in the wound area of this specimen was about
0.2. A considerable increase in the expression of p53 (r > 0.5) was first found
in a wound aged 8 days and in wounds with postinfliction intervals ranging
between 3 and 11 weeks, where the ratio of positive cells was between 0.40 and
0.64. Therefore, it can be calculated that r-values of at least 0.5 indicate a
postinfliction interval of approximately 1 week or more. Since comparably low
numbers of positively stained fibroblastic cells were found in specimens with an
advanced wound duration, reliable information for a forensic wound age estimation
can only be provided by positive results.
PMID- 9646157
TI - Cardiac troponin I (cTn I) and the postmortem diagnosis of myocardial infarction.
AB - In clinical practice several biochemical markers are used for the diagnosis of
myocardial infarction. Because of its extremely high specificity for myocardial
damage, cardiac troponin I (cTn I) is frequently used. The aim of this study was
to evaluate the diagnostic efficacy of postmortem cTn I determinations in
pericardial fluid and serum and to compare these results with other biochemical
markers and with structural findings used to diagnose acute myocardial ischaemia.
We studied 89 cadavers with a mean age of 51.38 +/- 2.04 (SD 19.27 years). Cases
were allocated to 1 of 4 diagnostic groups depending on the probable intensity of
myocardial damage and cause of death. In pericardial fluid we obtained
statistically significant differences for the four biochemical parameters, while
in serum myosin heavy chains and myoglobin showed statistically significant
differences. The highest levels of biochemical markers in pericardial fluid were
observed in subjects who had died from definite myocardial infarction.
PMID- 9646158
TI - DNA-typing of cellular material on current conductors.
AB - The examination of deaths due to electricity may require a comparison between
current marks on the body and the electrodes suspected to have caused them.
Normally the identification of the responsible electrode is carried out by
analysing metal traces on the current marks. We however examined the conductor
for traces of biological material after experimentally produced current marks.
The surfaces of the conductors were investigated using a low-power macroscope and
burnt tissue could always be recognised. Subsequently, all electrodes were
carefully swabbed, extracted with chelex and typed for short tandem repeat
polymorphisms using PCR. This procedure was successful in all cases. Therefore,
DNA analysis can be a powerful tool to supplement conventional scene
reconstruction in cases of deaths due to electricity.
PMID- 9646159
TI - Tetranucleotide STR system D8S1132: sequencing data and population genetic
comparisons.
AB - In the present investigation of the D8S1132 locus 31 selected alleles were
sequenced. In total there were 9 distinguishable alleles found to increase in
size by regular 4 bp increments from 134 to 170 bp with a repeat array following
the pattern (TCTA)n TCA (TCTA)n. One-third of the sequenced alleles exhibited an
altered repeat sequence TCTG TCTA at the 3' flanking region of the repeat array.
A nomenclature for the designation of D8S1132 alleles is proposed on the basis of
this sequence data and in accordance with the ISFH recommendations. The allele
distribution of the D8S1132 locus has been investigated in three German
populations (Halle-, Munster-, and Wiesbaden area) with frequencies ranging from
0.004 to 0.24. No deviation from Hardy-Weinberg equilibrium could be observed.
The heterozygosity was 0.83 and the discrimination power 0.96 for the Halle
population.
PMID- 9646160
TI - Subtyping and characterization of D1S80 alleles in a Japanese population using
PCR-RFLP.
AB - In a Japanese population study of the D1S80 locus 24 alleles ranging from allele
16 to allele43 were analysed using PCR-RFLP. As two repeat units were found to
contain the restriction cleavage site (CCAGG) for EcoRII, we digested the alleles
with EcoRII, separated the digested fragments on polyacrylamide gels and stained
with ethidium bromide. Of the 24 alleles 11 band patterns were identified and
tentatively labeled E1 to E11. A total of 42 subtypes were detected in a
population group of 111 unrelated individuals. All samples of allele 18 were of
the E3 type, while about 60% of the allele24 samples were of the E4 type and
about 40% were of the E8 type. The third most frequent allele (allele30)
contained four types, E4, E8, E5 and E6. No deviations from Hardy-Weinberg
equilibrium were observed. Since this method could differentiate those samples
which had the same length but different sequences, it is quite useful for
paternity testing and individual identification.
PMID- 9646161
TI - Citalopram concentrations in samples from autopsies and living persons.
AB - Concentrations of citalopram in medicolegal samples from 92 autopsies and 27
living persons are described. In autopsy cases in which citalopram alone was the
cause of death, concentrations ranged from 2.0 to 6.2 mg/kg whole blood. In
autopsy cases in which citalopram together with other substances was considered
to be the cause of death, the concentrations of citalopram ranged from 0.6 to 5.2
mg/kg whole blood. In autopsy cases toxic concentrations ranged from 0.4 to 0.9
mg/kg whole blood and therapeutic concentrations from 0.03 to 0.6 mg/kg whole
blood. In samples from living persons the concentrations of citalopram in whole
blood were 0.02 to 0.3 mg/kg.
PMID- 9646162
TI - Clinical and morphological aspects of death due to liquid nitrogen.
AB - A 24-year-old student died while filling flasks with liquid nitrogen. The arms,
legs and back were frozen and the face, ears and neck showed a dark red and livid
colour with horizontal lines of demarcation. In the electrocardiogram, the heart
showed asystolia followed by wide ventricular complexes. The patient was
intubated orally as the situs of the larynx and pharynx showed no pathology
findings. Cardiopulmonary resuscitation was carried out and terminated after 90
min. Unfortunately, the body temperature was not measured. The gas analysis of
venous blood showed metabolic acidosis and oxygen deficiency. The student had
worked alone with nitrogen, without opening the windows and without a working
ventilation system. While filling the third flask he lost consciousness. As
nitrogen does not cause characteristic prodromal signs he laid on the floor and
was unable to help himself. The liquid nitrogen which was still escaping spread
over the floor and vaporized. The student died from asphyxia due to oxygen
deficiency in an atmosphere of nitrogen.
PMID- 9646163
TI - Suicide with moclobemide and perazine.
AB - A 51-year-old woman who was diagnosed as suffering from depression was found dead
in her flat. The autopsy revealed no morphological changes sufficient to explain
death. Toxicological analysis was performed and the drugs moclobemide (49.9
mg/l), perazine (1.27 mg/l) and some metabolites were identified in the blood. A
combined drug intoxication resulting in synergistic effects to cardiovascular
disorders was proposed as the cause of death.
PMID- 9646164
TI - Sudden death associated with myxomatous transformation of the mitral valve in an
8-year-old boy.
AB - An 8-year-old boy suffered a cardiac arrest while playing soccer. In contrast to
a similar event at the age of 5 years, resuscitation was not successful. At
autopsy, the cardiac findings were of a myxomatous transformation of the mitral
valve with lacerations of the posterior cusp and the left vestibular endocardium
and left ventricular hypertrophy. Sudden death due to arrhythmias in association
with a myxomatous mitral valve is a rare event with only about 100 cases
published world-wide. To our knowledge, the present case probably reports the
youngest affected individual who died of this pathological condition.
PMID- 9646165
TI - A case of delayed death after accidental intravenous injection of thrombin.
AB - A delayed death which occurred after accidental injection of thrombin into the
right subclavian vein is described. The patient was given heparin intravenously
after an erroneous intravenous injection of thrombin and died from lobar
pneumonia 3 months afterwards without any apparently ill effects on the
circulation of the body except for the brain. At autopsy, however, a large
thrombus was observed extending continuously from the superior vena cava to the
pulmonary trunk, via the right atrium and ventricle. From the results it was
concluded that there was a causal relationship between the inadvertent
intravenous administration of thrombin and death.
PMID- 9646166
TI - Car crash after massive ingestion of digoxin and midazolam.
AB - In a case where a 32-year-old man lost control of his vehicle, urine and blood
samples were taken 6 h after the crash for toxicological investigations. In the
hospital, the driver admitted consumption of some drugs, in particular digoxin
and midazolam just before the crash which corresponded to the results of blood
analyses. Toxicological findings indicated the presence of digoxin at 12.9 ng/ml
and midazolam at 7 ng/ml in the blood. These results suggested that at the moment
of the crash digoxin and midazolam blood levels were in the range of toxic and
therapeutic concentrations, respectively. Therefore the respective roles of the
drugs in the impairment of the ability to drive at the moment of the crash is
discussed.
PMID- 9646167
TI - Proof of fatal air embolism.
AB - Venous air embolism is a rare cause of death. Entry of gas into the circulation
is caused by trauma, mostly surgical or therapeutic, and sometimes resulting from
criminal intervention. The detection of air embolisms requires special
precautions during autopsy. An aspirometer has to be used for the detection,
measurement and storage of gas originating from the heart ventricles. The
aspirometer has to be filled completely with distilled water containing two drops
of Tween 80 to reduce the surface tension of the water and to prevent adherence
of small air bubbles to the wall of the aspirometer. Subsequently the gas has to
be analysed by gas chromatography. When the results correspond with the main
criteria defined by Pierucci and Gherson [2] the diagnosis "air embolism" is
justified. The technique for the detection of air embolism is simple but requires
a careful procedure which is described in detail.
PMID- 9646168
TI - Study on the STR TPOX in an Italian and an Austrian population using two
different primer pairs and three different electrophoretic methods.
AB - The short tandem repeat TPOX was studied using two different pairs of primers and
three different electrophoretic methods with the aim of optimizing and
standardizing the typing conditions for this locus. A genetic population study
was subsequently conducted on two population samples from Central Italy (151
individuals) and from Austria (153 individuals) and compared using an R x C
contingency table. With the aim of using this system for forensic samples,
differences in sensitivity between the methods utilized were studied and several
parameters of forensic interest for the two populations (PD, MEC, MEP, pM, PIC)
were calculated. A new multiplex system for the loci CSF1PO, TPOX and CD4 is also
presented.
PMID- 9646169
TI - Y chromosome polymorphisms and haplotypes in west Saxony (Germany).
AB - In order to apply a set of useful and high polymorphic Y-STRs in paternity
testing, we performed a population genetic study from Saxony. The allele
distributions of the systems DYS19, DYS385, DYS389I/II and DYS390 were
investigated in a sample of 250 unrelated males from the area of Leipzig. PCR
products were detected using native polyacrylamide gel electrophoresis as well as
capillary electrophoresis and GenScan Software on the ABI Prism 310 DNA
sequencer. Haplotype frequency data of 164 different types were obtained which
show that these four systems are very useful for special cases of paternity and
forensic stain analysis. In addition several confirmed father-son pairs were
examined using the paternity cases of the institute. One mutation was found in
the system DYS390 and sequencing data are presented.
PMID- 9646170
TI - Metal pins fired from unmodified blank cartridge guns and very small calibre
weapons--technical and wound ballistic aspects.
AB - Blank cartridge guns are generally regarded as being harmless and are not
considered to be firearms in most countries. A comparison of the legal situations
in Germany and Austria concerning weapons is given. There have been several
reports of serious injuries and even fatalities due to these weapons. Ballistic
experiments show that even unmodified blank cartridge guns and very small calibre
weapons can fire wire nails and can inflict potentially fatal injuries even at
distances of 50 cm. Two serious injuries inflicted by metal pins fired from a
blank cartridge gun and a very small calibre weapon are reported. These cases
suggest that such weapons should also be considered handguns in the legal sense.
PMID- 9646171
TI - Allele frequency distributions of the polymorphic STR loci HUMVWA, HUMFES,
HUMF13A01 and the VNTR D1S80 in a Filipino population from Metro Manila.
AB - Allele frequency distributions at the short tandem repeat (STR) loci HUMVWA,
HUMFES, HUMF13A01 and of the variable number of tandem repeat (VNTR) locus D1S80
were determined in a Filipino population from Metro Manila (103 individuals) by
use of the polymerase chain reaction (PCR) followed by polyacrylamide gel
electrophoresis (PAGE). The exact test demonstrated that all four loci had no
deviations from Hardy-Weinberg equilibrium (HWE) with the only reservation that
the exact test p-value for F13A01 is weak. The discriminating power is 0.82 for
D1S80, and the expected exclusion chance is 0.85 for F13A01, 0.83 for FES, and
0.93 for VWA. The observed heterozygosity rates are 0.63 for D1S80, 0.66 for
F13A01, 0.67 for FES, and 0.80 for VWA. The exact test for independance between
all loci gave a p-value of 0.0195. This is the first time that Filipino
population data of DNA loci of forensic importance are reported.
PMID- 9646172
TI - Self-implanted subcutaneous penile balls--a new phenomenon in western Europe. M.
A. Rothschild et al. Int J Legal Med (1997) 110: 88-91.
PMID- 9646173
TI - Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist.
AB - IL-1 (IL-1 alpha or IL-1 beta) is the prototypic "multifunctional" cytokine.
Unlike the lymphocyte and colony stimulating growth factors, IL-1 affects nearly
every cell type, and often in concert with other cytokines or small mediator
molecules. Although some lymphocyte and colony stimulating growth factors may be
therapeutically useful, IL-1 is a highly inflammatory cytokine and the margin
between clinical benefit and unacceptable toxicity in humans is exceedingly
narrow. In contrast, agents that reduce the production and/or activity of IL-1
are likely to have an impact on clinical medicine. In support of this concept,
there is growing evidence that the production and activity of IL-1, particularly
IL-1 beta, are tightly regulated events as if nature has placed specific "road
blocks" to reduce the response to IL-1 during disease. In addition to controlling
gene expression, synthesis and secretion, this regulation extends to surface
receptors, soluble receptors and a receptor antagonist. Investigators have
studied how production of the different members of the IL-1 family is controlled,
the various biological activities of IL-1, the distinct and various functions of
the IL-1 receptor (IL-1R) family and the complexity of intracellular signaling.
Mice deficient in IL-1 beta, IL-1 beta converting enzyme (ICE) and IL-1R type I
have also been studied. Humans have been injected with IL-1 (either IL-1 alpha or
IL-1 beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1
specific receptor antagonist (IL-1Ra) has also been tested in clinical trials.
PMID- 9646174
TI - Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular
aspects.
AB - Interleukin-10 is an ubiquitous cytokine which plays a major regulatory role in
the course of inflammatory responses by downregulating the synthesis of
cytokines. In this paper, we summarize the major biological properties of IL-10
and the current knowledge of the molecular mechanisms by which IL-10 inhibits the
expression of genes encoding proinflammatory cytokines. We then review the
factors upregulating IL-10 synthesis and we present the concept that IL-10 is a
stress cytokine produced not only in response to microbial pathogens but also to
cellular injuries of diverse origins.
PMID- 9646175
TI - Signaling and functional properties of interleukin-16.
AB - Interleukin-16 is secreted from a variety of immune cells as a peptide of 17 kDa
which aggregates into tetrameric form essential for IL-16s direct interaction
with and cross linking of its receptor, the CD4 antigen. IL-16 stimulation of
CD4+ cells results in the induction of cell motility, and in addition can
function as a competence growth factor for CD4+ lymphocytes. These activities
suggest that IL-16 could play a role in the accumulation and activation of CD4+
cells recruited to sites of inflammation. Along those lines, IL-16 has been
identified at sites of inflammation associated with several different disease
states. Its function as a competence growth factor specifically for CD4+ T cells
may be useful for immune reconstitution in immunodeficiency diseases such as
AIDS.
PMID- 9646176
TI - Interleukin-17.
AB - The particular interest of IL-17, a homodimeric cytokine of about 32 kDa, is the
strict requirement for an activation signal to induce its expression from a
rather restricted set of cells, human memory T cells or mouse alpha beta TCR+CD4
CD8- thymocytes. In contrast with the tightly controlled expression pattern of
this gene, the IL-17 receptor, a novel cytokine receptor, is ubiquitously
distributed but apparently more abundant in spleen and kidney. In addition to its
capture by the T lymphotropic Herpesvirus Saimiri (HVS), this cytokine is
inducing the secretion of IL-6, IL-8, PGE2, MCP-1 and G-CSF by adherent cells
like fibroblasts, keratinocytes, epithelial and endothelial cells. IL-17 is also
able to induce ICAM-1 surface expression, proliferation of T cells, and growth
and differentiation of CD34+ human progenitors into neutrophils when cocultured
in presence of irradiated fibroblasts. In vitro, IL-17 synergizes with other
proinflammatory signals like TNF alpha for GM-CSF induction, and with CD40-ligand
for IL-6, IL-8, RANTES and MCP-1 secretion from kidney epithelial cells. In vivo,
injection of IL-17 induces a neutrophilia, except in IL-6-KO mice. The
involvement of IL-17 in rejection of kidney graft has also been demonstrated. The
role of this T cell secreted factor in various inflammatory processes is
presently investigated.
PMID- 9646177
TI - TGF-beta: a balancing act.
AB - Regulation of developmental processes as well as host defense and repair
mechanisms requires the maintenance of a delicate balance of positive and
negative regulatory signals. TGF-beta, a molecule known for its many diverse
activities, can promote or inhibit cell growth and function. Disruption of the
balance between these opposing activities can contribute to aberrant development,
malignancy, or pathogenic immune and inflammatory responses. TGF-beta transgenic
mouse studies highlight the essential function(s) of TGF-beta and its receptors
and provide insight to potential therapeutic approaches to manipulate TGF-beta
expression.
PMID- 9646178
TI - Transcriptional control of cytokine genes.
AB - With antigen stimulation, cytokine genes are coordinately expressed in T cells.
However, the optimal signals or helper T cell subset specificity for each
cytokine gene expression differ. Mechanisms probably exist that transmit
extracellular signals into the nucleus, thereby coordinately turning on and off
transcriptional machinery in a signal-specific or cell type-specific manner. We
compare here the regulation of cytokine genes and discuss possible mechanisms of
coordinated and differential regulation of cytokine genes.
PMID- 9646179
TI - Cytokine receptors: structures and signal transduction.
AB - The characteristic features of cytokines are functional pleiotropy and
redundancy. Each cytokine is produced by a variety of cell types and acts on a
wide range of target cells and tissues. Many cytokines have overlapping
biological activities in the same cells. It was originally thought that each
cytokine has a specific receptor and a unique signal transduction system.
However, extensive studies on cytokines and their receptors revealed that many
cytokines share receptor subunits and signal transduction system, and that
biological functions of a single cytokine can vary depending on the status of the
cells. Therefore, it is important to know the structure and function of cytokine
receptors to understand the pleiotropy and redundancy as well as specificity of
cytokines. Among signal transduction pathways, recently identified Jak/STAT
pathway, which connects activation of the receptor complexes and transcription of
various genes directly, would give us further insights in the mechanisms of
cytokine action.
PMID- 9646180
TI - The chronobiology of human cytokine production.
AB - Cytokine production in human whole blood exhibits diurnal rhythmicity. Peak
production of the pro-inflammatory cytokines IFN-gamma, TNF-alpha, IL-1 and IL-12
occurs during the night and early morning at a time when plasma cortisol is
lowest. The existence of a causal relationship between plasma cortisol and
production is suggested by the finding that elevation of plasma cortisol within
the physiological range by the administration of cortisone acetate results in a
corresponding fall in pro-inflammatory cytokine production. Cortisol may not be
the only neuroendocrine hormone that entrains cytokine rhythms; other candidates
include 17-hydroxy progesterone, melatonin and dihydroepiandrostene dione
(DHEAS). The finding of diurnal cytokine rhythms may be relevant to understanding
why immuno-inflammatory disorders such as rheumatoid arthritis or asthma exhibit
night-time or early morning exacerbations and to the optimisation of treatment
for these disorders. Diurnal rhythmicity of cytokine production also has
implications for the timing of blood samples drawn for diagnostic T-cell assays.
Finally, diurnal rhythmicity of immune function suggests that the nature of an
immune response, for example in response to vaccination, may be modified by the
time of day of antigen administration and raises the possibility that immune
responses could be therapeutically manipulated by co-administration of immuno
regulatory hormones such as glucocorticoids.
PMID- 9646181
TI - Cytokines in hematopoiesis.
AB - Hematopoiesis is the process by which mature, functional progeny of the eight
major lineages of blood cells are produced from a hierarchy of progressively less
mature progenitor and stem cells. The control of hematopoiesis involves intimate
cellular interactions between developing blood cells and stromal elements as well
as regulation by soluble cytokines, that may act locally in the bone marrow
environment or at remote tissue sites. In excess of twenty cytokines that
stimulate the production and/or function of hematopoietic cells have now been
cloned and are available in purified, recombinant form. The colony-stimulating
factors, erythropoietin and the recently discovered thrombopoietin are key
regulators of granulocyte/macrophage, erythroid and megakaryocyte/platelet
production respectively. The activities of these cytokines have been extensively
studied, both in vitro and in vivo, and recent analysis of mice genetically
engineered to lack these regulators or their cell surface receptors have provided
profound insights into their essential physiological roles. These studies have
culminated in the development of these cytokines as valuable clinical reagents.
PMID- 9646182
TI - Cytokines and cancer.
AB - The relationships between cytokines and cancer are multiple and bidirectional. On
the one hand, cytokines may directly influence carcinogenesis and metastasis by
modifying the tumor phenotype. On the other hand, during tumor progression,
modifications of the cytokine expression in the tumor environment may be induced
by the tumor cells, leading to a state of immunosuppression reflected by low
cytokine expression in tumor stroma. Cytokines also play a role by stimulating
the host immune system to generate anti-tumor specific responses. Finally, the
use of cytokines as anti-tumor agents has led to objective clinical responses in
about 15-25% of patients with metastatic melanoma or renal cell carcinoma, which
presents the basis for the development of promising immunotherapeutic approaches
for cancer therapy.
PMID- 9646183
TI - Cytokines and chemokines in HIV infection: implications for therapy.
AB - HIV infection is associated with both a hyperactivity of the immune system and
decreased immune responses against specific antigens. A similar pattern is
observed when considering cytokine production in HIV-infected patients. Several
cytokines are spontaneously produced at an increased level, whereas other
cytokines playing an important role during cell-mediated immune responses are
produced at a low level following stimulation. This deregulation of cytokine
production may participate to the immune deficiency, both by impairing immune
responses and by accelerating CD4+ T lymphocyte destruction. Chemokine receptors
have recently been shown to function as coreceptors for the virus, and to govern
its cellular tropism. Heterogeneous expression of chemokine receptor may
contribute to differences in infectability as well as in rate of progression of
the disease between individuals. Better understanding of the role of cytokines
and chemokines in HIV infection suggests new therapeutic approaches where
administration of cytokines or cytokine antagonists may allow the immune system
to function in better conditions, to stimulate antiviral and antiinfectious
immune defenses, and to limit viral spread.
PMID- 9646184
TI - Characterization of the haemoglobin-mediated inhibition of the enzymatic activity
of bovine serum amine oxidase.
AB - Haemoglobin has been previously identified as responsible for the decreased
enzymatic activity of copper bovine serum amine oxidase (BSAO) in suspensions of
human or bovine hemolyzed erythrocytes [Marcocci, L., Pietrangeli, P., Befani,
O., Mavelli, I., & Mondovi', B. (1991b) Life Chem. Report, 9, 171-177]. This is
confirmed by present results on bovine methaemoglobin. Bovine globin and horse
skeletal muscle mioglobin showed a similar inhibiting ability, but neither bovine
serum albumin nor cytochrome c inhibited BSAO activity under the same
experimental conditions. The inhibitory effect of bovine haemoglobin was
dependent on pH only at high buffer ionic strength. It was highest in
physiological conditions (PBS) where haemoglobin acted as a reversible non
competitive inhibitor of BSAO activity, with apparent Ki of 0.5 mM at 37 degrees
C. The inhibition was unaffected by partial BSAO deglycosylation (40% of glucidic
residues removed) but decreased when haemoglobin lysine groups were derivatised
using citraconic anhydride. A possible molecular mechanism underlying the
inhibitory effect is discussed.
PMID- 9646185
TI - Effects of wortmannin on human neutrophil respiratory burst and phagocytosis.
AB - Modulation of neutrophil response to naturally occurring stimuli is important to
avoid host tissue injure. Both soluble and particulate stimuli may induce
superoxide anion generation in human polymorphonuclear leukocytes. Recently
wortannin has been shown to inhibit the N-formyl-methionyl-leucyl-phenylalanine
(fMLP) induced activation of respiratory burst via phosphatidylinositol 3-kinase.
However no data are available about the effect of the inhibitor on the
respiratory burst induced by a particulate stimulus. In this paper we studied the
effect of wortmannin on E. coli induced respiratory burst and phagocytosis by
flow cytometry, which allows the quantitation of both H2O2 production and
ingested bacteria in whole blood samples without the need of purification and
concomitant manipulation of the cells. The effects of worthmannin on fMLP-induced
chemotaxis was also examined by the under agarose method. Neither the E. coli nor
the fMLP-induced responses were blocked by wortmannin, suggesting that PI 3
kinase activity is not required to activate these neutrophil functions. Since it
is known that the respiratory burst elicited by fMLP is blocked by wortmannin,
our results suggest that the generation of oxygen radicals is controlled via
different signal transduction pathways, depending on the agonist used.
PMID- 9646186
TI - Prolonged in vitro culture modifies the surface lipid composition of murine
melanoma cell lines.
AB - Lipid composition of two murine melanoma cell variants (B16, without malignant
properties and B16-F10, with high metastatic activity), has been examined at
different stages of growth. The aim of the work was to identify cell surface
modifications due to the time length of in vitro culture, that could be one
variable to consider when metastatic potential is studied. Some of the analyzed
parameters (ganglioside- and glycoprotein-bound neuraminic acid, cholesterol,
neutral glycolipids, phospholipids, triacylglycerols) undergo statistically
significant variations at the various passages in B16-F10 line. Fatty acids
composition of the phospholipidic fraction was changed only at the last observed
passage (100) in B16 line. No one of the examined parameters justifies the
ability of B16-F10 cells to invade distant districts and to originate new tumors.
Probably detailed lipid analysis on cellular subfractions, as already performed
in this study on total lipid extract of the whole cell, could be a valuable tool
to identify differences related with metastatic potential.
PMID- 9646187
TI - Liver transplants in Italy: organizational aspects and inter-regional
differences.
PMID- 9646188
TI - Screening for colorectal cancer: the light at the end of the tunnel.
PMID- 9646189
TI - Should we test for lactose malabsorption?
PMID- 9646190
TI - Peptic ulcer treatment today--is there a role for maintenance therapy?
PMID- 9646191
TI - Quality control study of H2 breath testing for the diagnosis of carbohydrate
malabsorption in Italy. The "Tenue Club" Group.
AB - BACKGROUND AND AIMS: H2 breath testing is increasingly used in Italy. The aim of
this multicenter study was to assess the accuracy of this technique in the
diagnosis of carbohydrate malabsorption. METHODS: An anonymous questionnaire was
used to collect information about H2 breath testing methods and to design the
quality control study. Fifteen out of 23 laboratories responded to the
questionnaire and 12/23 completed the entire study. RESULTS: The survey revealed
that a large variety of H2 testing methods are employed in Italy, but none have
been previously tested for accuracy. This prospective study showed that these
tests fail to identify > 20% of patients with malabsorption. In contrast, a new
method based on single H2 breath measurement at 6 hours after lactulose ingestion
and a cutoff value of greater than 5 ppm, had a sensitivity of 92% +/- 4% and a
specificity of 94% +/- 0.5%. Increasing the cut-off to 10 ppm resulted in a
sensitivity of 88% +/- 9% and a specificity of 100%. This improved accuracy was
obtained with a much simpler testing procedure in which only one breath sample is
analyzed, in contrast to the baseline and multiple subsequent samples that are
analyzed using the currently employed techniques. CONCLUSIONS: A great
improvement in the accuracy of the H2 breath test, as well as a considerable
saving in terms of time and costs, may be possible through the use of a new,
simplified H2 breath test followed by careful H2 analysis.
PMID- 9646192
TI - Maintenance therapy with colloidal bismuth subcitrate reduces duodenal ulcer
relapse.
AB - AIM: To investigate the efficacy and safety of daily low-dose colloidal bismuth
subcitrate in reducing duodenal ulcer relapse. DESIGN: Double-blind, double-dummy
group comparative clinical trial with random allocation. Healing Phase: colloidal
bismuth subcitrate 240 mg twice daily vs ranitidine 150 mg twice daily for up to
12 weeks. Maintenance Phase: nightly, colloidal bismuth subcitrate 120 mg vs
ranitidine 150 mg vs placebo for up to 12 months (high-risk patients received
active treatment only). ASSESSMENT: clinical, endoscopy, random blood bismuth
levels (and rapid urease test for Helicobacter pylori in a subgroup). PATIENTS:
194 with active duodenal ulcer. OUTCOME: Cumulative healing at 12 weeks was 93%
on colloidal bismuth subcitrate (of 92 patients) and 97% on ranitidine (of 102
patients). Relapse at 1 year was significantly less on active treatment as
follows: placebo (50 patients) 60%; ranitidine (71 patients) 21%; colloidal
bismuth subcitrate (64 patients) 33%. This was independent of the results of the
rapid urease test which was positive in 78%, 88% and 76% of the patients
respectively. Treatment was well tolerated. The highest median blood bismuth
level (mcg/L) was 25 in the healing phase and fluctuated between 6 and 10 in the
maintenance phase. CONCLUSIONS: Colloidal bismuth subcitrate, 120 mg nightly, is
effective in reducing duodenal ulcer relapse and is well tolerated.
PMID- 9646193
TI - Gastrointestinal carcinoid tumours. A population-based study.
AB - AIM: The aim of this study was to provide further information on the descriptive
epidemiology of gastrointestinal carcinoids. METHODS: Data was drawn from the
Tuscany Tumour Registry, a population-based registry active in the province of
Florence. All the carcinoid tumours reported for the period 1985-1991 in
gastrointestinal organs were analysed. Incidence, mortality and survival data are
presented. RESULTS: There were 53 gastrointestinal carcinoid tumours in 29 males
and 24 females. The site distribution was: 19 small intestine, 8 colon, 7
appendix, 6 stomach, 6 rectum, 1 large bowel (not specified), and 6 from known
metastases. The overall age-adjusted incidence rate was 0.42/100,000. At
diagnosis, 33 carcinoids showed evidence of invasion and/or spreading. Seven
patients had two independent tumours. As of 31.12.94, nineteen patients had died.
The overall observed and relative 5-year survival rates were 66.1% and 75.1%,
respectively. CONCLUSIONS: In the province of Florence, the incidence of
gastrointestinal carcinoid tumours is low. Probably, this result, is in part due
to the low autopsy rate. The overall survival rate is quite good, with the best
prognosis seen for appendiceal carcinoids and the worst for colon and stomach
carcinoids. 1.9% of the patients had a further tumour diagnosis.
PMID- 9646194
TI - Clinicopathological features of early gastric cancer in younger versus older
patients in a high incidence area of northern Italy.
AB - AIMS: The relationship between the clinicopathological features of early gastric
cancer and age were analysed in a retrospective study of 168 patients. METHODS:
168 patients, residents of the Region of Cremona, who had undergone surgery in
the period 1978 to 1990 for early gastric cancer, were divided into two groups by
age and compared. Group I (n = 89) consisted of patients less than 65 years of
age and Group II (n = 79) of patients between 66 and 85 years of age. RESULTS:
There were no significant differences between the two groups with respect to the
sex ratio, tumour size, depth of tumour invasion, and 5-year survival rate. Group
I patients showed more lymph node involvement (p < 0.01), cancer of the diffuse
histological type (p < 0.01), and cancers located in the gastric body (p < 0.05).
Conversely, Group II exhibited more cancers of the protruded (p < 0.05) and
intestinal histological type (p < 0.01), and more adenomatous residue (p < 0.01).
CONCLUSIONS: Our findings suggest that early gastric cancer may present
differently in different age groups; persons 65 years of age and older are more
likely to have early gastric cancer of the slow-growing type than middle-aged
patients.
PMID- 9646195
TI - Differential effect of stress on gastric somatostatin, prostaglandin E and
gastrin release in the rat.
AB - BACKGROUND: The relationship between gastric mucosal damage induced by stress,
peptides present in the gastric mucosa and is not clear. Aim of this study was to
determine whether cold-restraint stress affected the release of gastric
somatostatin, gastrin and in the isolated perfused stomach preparation. METHODS:
Male Sprague-Dawley rats were used, 12 cold-restraint stressed and 12 unstressed
controls. 4 additional unstressed rats were treated with aspirin (100 mg/kg
p.o.). After 30 minutes, isolated stomachs were perfused for 50 minutes with
Krebs-Ringer buffer added with isoproterenol or carbamylcholine plus somatostatin
14 or carbamylcholine alone, somatostatin, gastrin and prostaglandin E2 release
in the portal vein effluent were measured by radioimmuno-assay. Histology of the
gastric mucosa was obtained from a further 4 stressed and 4 unstressed rats.
RESULTS: In the stomach from stressed animals, the somatostatin response to
isoproterenol and the prostaglandin E2 response to carbamylcholine plus
somatostatin were significantly lower than in the controls, whereas gastrin
response to carbamylcholine was enhanced by stress. Treatment with aspirin
abolished the prostaglandin E2 response to stimulation. Gastric mucosa histology
from stressed and unstressed animals showed no significant lesions. CONCLUSIONS:
The inhibition of gastric somatostatin and prostaglandins release coupled to an
enhanced acid stimulatory influence appear to antidate gastric mucosal injury and
should play a role in the stress ulcer genesis.
PMID- 9646196
TI - Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with
virus-induced chronic liver disease and response to interferon.
AB - BACKGROUND & AIMS: Oncogenes were activated in experimental models of hepatocyte
regeneration. We studied the intrahepatic expression of c-fos, c-myb and c-myc
protooncogenes in 117 patients with chronic liver disease: 12 with hepatitis B,
15 HBsAg carriers, 73 with hepatitis C and 17 with non-viral liver damage.
METHODS: Oncoproteins were detected by indirect immunofluorescence using high
affinity and monoclonal antibodies. Grade and stage of liver damage were measured
by numerical score. RESULTS: Nuclear c-fos and/or c-myb were found in 7 (58.3%)
hepatitis B patients, in 38 (52%) hepatitis C patients, in 1 (6.6%) HBsAg carrier
(p < 0.004) and in none of the non-viral disease patients (p < 0.0001). In no
case was c-myc detected. Oncoproteins were correlated with the histological
activity index (p < 0.0001) and its components: lobular degeneration and
periportal necrosis (p < 0.0001), fibrosis (p < 0.005) and portal inflammation (p
< 0.03). Thirty-one chronic hepatitis C patients were treated with alpha-IFN: 9
out of 14 oncoprotein-positive patients (64%) were non-responders, 5 (36%)
relapsed and none was a sustained responder. Conversely 9 out of 17 (53%)
oncoprotein-negative patients, including 3 patients with histologically active
cirrhosis, showed long-term response (p < 0.005). CONCLUSIONS: Intrahepatic c-fos
and c-myb were detected in chronic viral hepatitis patients, but not in non-viral
liver diseases. Their expression correlated with the grade and stage of liver
disease and with poor response to alpha-IFN.
PMID- 9646197
TI - Syndromic variability of Wilson's disease in children. Clinical study of 44
cases.
AB - BACKGROUND: In children with Wilson's disease, no clinical or laboratory data are
specific for diagnosis as in adult age. AIM: Clinical aspects and parameters of
copper metabolism in a large series of pediatric cases are evaluated to establish
certain criteria for diagnosis and for correct treatment, even in difficult
cases. METHODS: In 44 children with Wilson's disease, clinical aspects,
histological features, laboratory parameters and data of copper metabolism have
been studied. Forty patients, treated with penicillamine, were followed up
(median 77 months). RESULTS: The 44 cases were classified as: asymptomatic forms
(nine cases, six of them siblings of affected subjects), chronic hepatitis (23
cases), hepatocerebral manifestations (four cases), decompensated cirrhosis (six
cases), fulminant hepatic failure with hemolytic anemia (two cases).
Ceruloplasmin levels were abnormal in 37 out of 43 tested cases, but normal in
six (14%) who showed high basal and after penicillamine load urine copper
excretion and increased hepatic copper content. Urine copper concentration was
pathological in 35 out of 42 tested cases (83%), but normal in seven patients
under six years. Hepatic copper levels were very high in all the 20 tested
patients. Under treatment, 27 children had favourable outcome. One patient showed
no evolution of disease, seven patients worsened because of non-compliance to the
therapy (one underwent successful liver transplantation) or severe side effects.
Five patients with failure died. CONCLUSIONS: Wilson's disease in children may
present with a broad clinical spectrum, but the liver involvement is by far the
most prevalent. The early diagnosis, based on clinical suspicion and results of
copper metabolism investigation (including hepatic copper content evaluation in
difficult cases) and appropriate treatment can prevent the progression of the
disease.
PMID- 9646198
TI - The cardiac evaluation of liver transplant recipients: a single center's
experience.
AB - OBJECTIVE AND BACKGROUND: Orthotopic liver transplantation is both a difficult
and a demanding surgical procedure. It is not unexpected that cardiovascular
dysfunction is present in some individuals being evaluated for liver
transplantation. Thus, all potential liver transplant recipients seen at this
center undergo a full cardiac evaluation prior to being accepted for
transplantation. The goal of this report was to review the components of the
cardiovascular evaluation utilized at the Oklahoma Transplantation Institute and
to determine their overall usefulness as well as the ability of the process to
identify individuals at high risk for a cardiac misadventure during liver
transplantation. MATERIALS AND METHODS: Between June 25, 1993 and June 30, 1995,
a total of 154 consecutive patients with chronic liver disease were evaluated.
The primary liver disease of each was established utilizing specific serologic
and biochemical tests, ultrasonographic and abdominal tomographic findings, as
well as hepatic histology results and hepatic iron and copper level
determinations. Each liver transplant candidate underwent a full cardiac
evaluation consisting of the following: nuclear ventriculography to estimate the
left ventricular ejection fraction (at rest and during exercise), right
ventricular ejection fraction, cardiac output, stroke volume and cardiac index;
uptake images using thallium and adenosine to identify foci of cardiac ischemic
or fixed defects; echocardiography to define the dimensions of the various
cardiac chambers, wall thicknesses, cardiac contractility and morphology of the
cardiac valves. Finally, coronary arteriography was performed in 26 patients
(16.9%) who were suspected of having clinically important coronary artery
disease. It should be noted that all of the cardiac evaluations were performed by
a single cardiologist. RESULTS: Eight of the 154 potential liver transplant
candidates (5.2%) were determined as not being eligible for liver transplantation
because of an inadequate cardiac status based upon an initial history and
physical examination. Forty-one of the remaining 146 patients (28.1%) underwent
liver transplantation. The remaining 105 subjects have not been transplanted for
reasons not related to the cardiac status. Eight of the 41 (19.5%) transplanted
patients had a clinically advanced cardiac problem recognized prior to liver
transplantation. Four of these eight required a specific cardiac intervention
prior to liver transplantation consisting of coronary bypass surgery (n = 1),
coronary artery balloon dilation (n = 2) or pericardiectomy (n = 1). The
remaining four patients required no pretransplant cardiac intervention and were
transplanted. None of these experienced any cardiac complications during, or in
the 3 months following, the liver transplant procedure. Only one patient
experienced a specific postoperative cardiac complication, consisting of an
episode of high grave A-V block requiring transplant placement of a cardiac
pacing device. This patient had hemochromatosis. CONCLUSIONS: Based upon this
experience, it can be concluded that coronary artery disease per se is not an
absolute contraindication for liver transplantation. With appropriate treatment,
liver transplantation can be performed safely in individuals with confounding
cardiac disease. Nuclear ventriculography and echocardiography are essential
procedures in evaluating potential liver transplant recipients in an effort to
exclude those with occult cardiomyopathy. Coronary arteriography is indicated
only in selected cases with evidence of cardiac ischemia or infarction.
PMID- 9646199
TI - Free radicals and not acetaldehyde influence the circulating levels of
glutathione after acute or chronic alcohol abuse: in vivo and in vitro studies.
AB - BACKGROUND: The oxidation of ethanol and acetaldehyde enhances the production of
various free radicals involved in membrane lipoperoxidation, and decreases
glutathione levels. AIMS: We evaluated the effects of acute and chronic ethanol
use in vivo, with or without the administration of S-adenosyl-methionine (SAME, 2
g I.v.), and the effects of ethanol and acetaldehyde in vitro, on the erythrocyte
levels of malonyldialdehyde and glutathione, and of its principal synthesizing
enzymes, gamma-glutamyl-cysteine-synthetase and glutathione-synthetase. METHODS:
Twelve healthy volunteers (age range 26-44 years, median 32 years) and 20 chronic
alcohol abusers without liver disease (age range 26-57 years, median 44 years)
were studied. Malonyldialdehyde was evaluated by thiobarbituric acid; glutathione
and its enzymes by high performance liquid chromatography using a fluorescent
detector. RESULTS: In the healthy subjects, an acute load of ethanol induced a
significant decrease in plasma levels of glutathione, which was inhibited by the
infusion of S-adenosyl-methionine. In the erythrocytes of alcoholic patients,
glutathione and glutathione-synthetase were decreased while malonyldialdehyde was
increased. In vitro, acetaldehyde did not affect either the glutathione or the
glutathione-related enzyme levels. CONCLUSIONS: Our data suggest that the
alterations in glutathione metabolism in the erythrocytes of alcoholics may be
due principally to the production of free radicals, as supported by the high
levels of malonyldialdehyde observed.
PMID- 9646200
TI - Clinical value of serum pancreatic enzymes in acute alcohol intoxication and
acute alcoholic pancreatitis.
AB - BACKGROUND AND AIMS: The aim of this study was to evaluate the incidence in the
serum of elevated levels of amylase, pancreatic isoamylase, and lipase in acute
alcohol intoxication among occasional drinkers and chronic alcoholics, and to
assess the diagnostic ability of the three enzymes for acute alcoholic
pancreatitis. PATIENTS AND METHODS: One-hundred and seventeen consecutive
subjects with acute alcohol intoxication but no abdominal pain (47 occasional
drinkers, 70 chronic alcoholics), and 17 with acute alcoholic pancreatitis were
studied. For all subjects serum amylase, pancreatic isoamylase, and lipase were
determined using commercially available kits. RESULTS: Among occasional drinkers,
serum amylase levels were abnormally high in 6 subjects (13%), whereas serum
pancreatic isoamylase and lipase were abnormally high in one, (2%). In chronic
alcoholics without abdominal pain serum amylase and lipase were abnormally high
in 10 subjects (14%) but serum pancreatic isoamylase in only 7 (10%). In patients
with acute alcoholic pancreatitis, serum amylase and pancreatic isoamylase were
abnormally high in 16 of the 17 patients (94%), whereas serum lipase was
abnormally high in all. CONCLUSIONS: Chronic alcohol abuse, but not occasional
alcohol intoxication, may cause pancreatic damage. Amylase, pancreatic isoamylase
and lipase determinations in the serum are all equally useful in the diagnosis of
acute alcoholic pancreatitis.
PMID- 9646201
TI - Percutaneous blind needle biopsy versus combined laparoscopic excisional and
guided needle biopsy in the diagnosis of liver disorders in pediatric patients.
AB - AIMS: The authors retrospectively analyzed the results of their experience with
combined laparoscopic excisional and guided needle biopsy in the determination of
chronic liver disease in children. PATIENTS AND METHODS: Between January 1986 and
January 1996, at the Division of Pediatric Surgery of the "Federico II"
University of Naples, eighty patients underwent laparoscopic liver biopsy to
evaluate a chronic liver disease. Patient ages ranged between 50 days and 16
years (mean 5.8 years). There were 41 girls and 39 boys. Fifteen of these
children (18.7%) were addressed to a surgeon because the previously performed
percutaneous blind needle biopsy was not sufficiently informative or because the
specimens were too small to allow chemical or biochemical tissue studies. In
these 15 patients, we performed a combination of laparoscopic guided needle
biopsy using a 14-gauge tru-cut needle together with an excisional biopsy on the
right lobe, using two additional 5-mm trocars. RESULTS AND CONCLUSION: The post
operative course was uneventful for all the patients. All patients were
discharged from hospital after 24 hours. A precise histological diagnosis was
made and biochemical tissue studies were possible after laparoscopic biopsy in
all 15 children. In our opinion, a combination of laparoscopic-guided needle
biopsy and laparoscopic excisional biopsy is more reliable than simple biopsy
alone for the diagnosis of cirrhosis in children with chronic liver disease.
PMID- 9646202
TI - Idiopathic recurrent pancreatitis successfully treated by hepatic vagotomy.
AB - Idiopathic recurrent pancreatitis and sphincter of Oddi disorders have been
increasingly found to be concomitant problems. Treatment of this condition
requires disruption of the integrity of the sphincter of Oddi. The case of a 16
year-old girl with sphincter of Oddi motor disorders and idiopathic recurrent
pancreatitis who was successfully treated with hepatic vagotomy. This result, if
confirmed, could add to our present knowledge of the physiopathology and
pathogenesis of sphincter of Oddi motor disorders.
PMID- 9646203
TI - Small cell carcinoma of the lung presenting as chylous ascites: a unique case.
AB - A 67-year-old female presenting with a history of weight loss and abdominal
distension was noted on examination to have ascites. Paracentesis revealed a
chylous ascites and chest radiography showed a right hilar enlargement with mid
zone infiltration. Abdominal computed tomography demonstrated retroperitoneal
lymphadenopathy and biopsy of this showed small cell undifferentiated carcinoma.
This appears to be the first documented association between metastatic small cell
carcinoma of the lung and chylous ascites.
PMID- 9646204
TI - Juvenile polyposis coli and associated anomalies. Review of the literature and
report of a case associated with hereditary spherocytosis.
AB - A case of juvenile polyposis associated with hereditary spherocytosis is
presented. All the anomalies associated with juvenile polyposis coli reported in
the literature are reviewed. The clinical consequences of such a report are
discussed along with the different forms of therapy for treating juvenile
polyposis coli. To our knowledge, this is the first report in the literature of
juvenile polyposis associated with hereditary spherocytosis.
PMID- 9646205
TI - Molecular diagnostics in hepatitis C virus infection: clinical applications.
Scientific Committee--"Tecnologie molecolari nella diagnostica delle epatopatie"
of the Italian Association for the Study of the Liver-AISF.
PMID- 9646206
TI - Omeprazole, nitrendipine, famotidine and stress-induced ulcers.
PMID- 9646207
TI - Caroli's disease: a case report.
PMID- 9646208
TI - Helicobacter pylori, intestinal metaplasia, cell proliferation and expression of
oncogenes.
PMID- 9646209
TI - What do we really know about Helicobacter pylori in gastric ulcer disease?
PMID- 9646210
TI - Appendectomy is an independent protective factor for ulcerative colitis: results
of a multicentre case control study. The Italian Group for the Study of the Colon
and Rectum (GISC)
AB - BACKGROUND: Different exogenous factors are believed to play a role in the
pathogenesis of ulcerative colitis. Smoking habits and other risk factors have
received much attention. It has recently been reported that appendectomy
decreases the risk of ulcerative colitis. AIM: Aim of the study was to further
examine the role of appendectomy in ulcerative colitis. METHODS: A large
multicentre case control study was performed. Cases were all patients with a
recent new diagnosis of ulcerative colitis (from 1990 to 1994) at participating
centres. One or two controls attending the orthopaedic and surgical units were
considered and matched to cases for age (+/- 5 years), sex and year of diagnosis.
A total of 536 cases and 755 controls were enrolled. Mean age of cases was 37.9
years (range 2-92). Assessment of exposure was done by examining the clinical
records and by interview, if necessary. Smoking habits, alcohol consumption, use
of oral contraceptives, type of occupation and area of residence were also
recorded. Odds ratio and 95% confidence intervals were calculated by conditional
logistic regression analysis. RESULTS: Forty-one out of the 536 cases (7.6%) and
150 out of the 755 controls (19.9%) had been submitted to appendectomy. A total
of 110 out of 536 cases (20.5%) and 135 out of 753 (17.9%) controls had had
tonsillectomy. Seven out of 41 cases and 15 out of 755 controls underwent
appendectomy for recurrent pain. In all ulcerative colitis patients, appendectomy
had been performed before the onset of disease. When data were adjusted for the
confounding variables, ulcerative colitis patients were less likely to have had
appendectomy compared with controls (odds ratio = 0.3, confidence interval = 0.19
0.48). There was no significant association of ulcerative colitis with
tonsillectomy (odds ratio = 1.09, confidence interval = 0.76-1.58). The well
recognized inverse association of ulcerative colitis with cigarette smoking was
also shown in this study. CONCLUSIONS: The present data emerging from a large
multicentre study, confirm that appendectomy has a protective role for the
development of ulcerative colitis.
PMID- 9646211
TI - Ulcerative colitis and appendectomy. What is the nature of the (negative)
association?
PMID- 9646212
TI - Effect of Helicobacter pylori eradication on gastric epithelial proliferation.
Relationship with ras oncogene p21 expression.
AB - BACKGROUND: Impaired changes in gastric epithelium proliferation have been
described in Helicobacter pylori infection, and a progressive increase of
proliferating cells has been shown with the progression of mucosal lesions. AIMS:
Purpose of this investigation was to study the effect of eradication on bacterium
induced proliferative changes, evaluated by the proliferating cell nuclear
antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein
p21, involved in early events of gastric carcinogenesis. PATIENTS AND METHODS:
This retrospective study was performed, before and after therapy, in five
different groups of patients with progressive stages of Helicobacter pylori
damage (N: normality; HG: histological gastritis with normal endoscopy; EHG:
histological gastritis with endoscopic chronic erosions; CIM: complete intestinal
metaplasia; IIM: incomplete intestinal metaplasia). RESULTS: Six months after
eradication, a normalization of PCNA LI was observed in the areas of gastritis,
but not in those of intestinal metaplasia, which showed on unchanged type.
Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only
associated to intestinal metaplasia. The protein was also expressed in the
cytoplasm in 3 patients with incomplete type. CONCLUSIONS: These results suggest
that the development of intestinal metaplasia may be associated with an
alteration in the control of gastric epithelium proliferation and could represent
an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes
are necessary for a complete progression to neoplastic disease. A long-term
follow-up on extension, type, proliferative situation and oncoprotein expression
in areas of intestinal metaplasia may be helpful to explain whether the present
data provide new information on the mechanism of Helicobacter pylori induced
gastric carcinogenesis.
PMID- 9646213
TI - Helicobacter pylori eradication in the healing and recurrence of benign gastric
ulcer: a two-year, double-blind, placebo controlled study.
AB - BACKGROUND: Helicobacter pylori infection is associated with idiopathic gastric
ulcer in about 90% of the cases, but only a few controlled studies aimed at
evaluating gastric ulcer healing and the natural history after Helicobacter
pylori-eradication have been carried out. OBJECTIVE: The aim of the present study
was to evaluate the efficacy of omeprazole coupled with amoxicillin in the
eradication of Helicobacter pylori and healing and prevention of gastric ulcer
recurrence. PATIENTS: Fifty-nine patients with active gastric ulcer were
randomized under double-blind conditions to receive either omeprazole 20 mg twice
daily for four weeks plus amoxicillin 3 g daily during the first and second week
(29 patients, Group A) or omeprazole .20 mg twice daily for 4 weeks plus placebo
for two weeks (30 patients, Group B). METHODS: Endoscopic studies were carried
out at the end of the 4 weeks treatment (or after 8 weeks in non-healed patients)
as well as 2, 6 and 12 months later. A total of 3 biopsies in the antrum, 3 in
the gastric body and at least seven at the edge of the crater were taken at each
endoscopic control for exclusion, of malignancy, histological detection of
Helicobacter pylori and for evaluation of gastric histology according to the
Sydney system. RESULTS: With intention to treat analysis, the percentage of
healing after 4 and 8 weeks was 86% and 100% in Group A patients and 86% and 93%
in Group B, respectively. Two patients dropped out in Group B for non medical
reasons. The percentage of eradication was 63% in Group A and 7% in Group B.
During a 12-month follow-up gastric ulcer relapsed in 20/32 (63%) of the
persistently Helicobacter pylori positive patients. Only two out 20 (10%)
Helicobacter pylori cured patients showed a gastric ulcer relapse and
Helicobacter pylori reinfection. Twenty out of 30 patients, still healed after 12
months, underwent endoscopic control after two years. A gastric ulcer relapse was
observed in three out of nine (33%) patients with persisting infection after
treatment. No gastric lesions, but one case of erosive oesophagitis were observed
in the 11 Helicobacter pylori-eradicated patients. CONCLUSIONS: In our
experience, Helicobacter pylori eradication does not favour gastric ulcer healing
but does positively influence the subsequent natural history.
PMID- 9646214
TI - Total gastrectomy: the influence of preserved duodenal transit and of pouch
reconstruction on abdominal symptoms, nutrient assimilation, and medico-social
functioning.
AB - BACKGROUND/AIMS: The aim of this retrospective study was to establish whether
patients with different reconstruction after total gastrectomy (duodenal bypass
without pouch (subgroup Ia, n = 88); duodenal bypass with pouch (subgroup Ib, n =
27); continuous duodenal transit (subgroup II, n = 27)) differ concerning
abdominal symptoms, nutrient assimilation, and medico-social functioning.
METHODS: The 142 patients (49 females, 93 males; mean age 57.2 years, (95%
confidence interval 55 to 59)) after potentially curative total gastrectomy for
gastric malignancy 500 days earlier (mean: 95% confidence interval 334 to 666)
were evaluated for abdominal symptoms, biochemical and haematological parameters,
endoscopic findings, small intestinal bacterial overgrowth, oro-caecal transit
time, objective signs of malassimilation, and the degree of medico-social
functioning. RESULTS: There were no significant differences between the subgroups
in any of the parameters examined. CONCLUSION: In this study, neither subjective
nor objective patient data support preference for any single mode of the examined
reconstructions after total gastrectomy. However, small patient numbers,
unstandardised reconstruction procedures and a recruitment bias might influence
these findings.
PMID- 9646215
TI - Use of a new thickened formula for treatment of symptomatic gastrooesophageal
reflux in infants.
AB - BACKGROUND: Paediatricians are familiar with infants complaining of regurgitation
and emesis from gastrooesophageal reflux. These subjects, usually growing
satisfactorily and healthy, are affected by "functional" or "symptomatic"
gastrooesophagel reflux and are treated with posture changes and thickened
feedings. AIM: To evaluate in infants with symptomatic gastrooesophageal reflux
the effect of a new formula (Nutrilon AR), containing carob flour/locus bean gum
as a thickening agent; both clinical features and oesophageal acid exposure were
evaluated. PATIENTS: Twenty-four infants (age range: 5-11 months; median age: 8
months; 8 females) presented at our Unit with a history of chronic postprandial
regurgitation. METHODS: During a 24-hour intraoesophageal pH test a traditional
formula thickened with rice flour at a concentration of 5% was alternated with
the formula Nutrilon AR; thereafter infants were randomly allocated to receive,
for two weeks, either a traditional thickened formula or the new formula, in
addition to posture changes. RESULTS: Intraoesophageal acid exposure was
significantly lower in the periods following the new formula than after
traditional formula; at the end of the treatment period patients receiving the
new formula had a more significant decrease of both symptomatic score and number
of episodes of emesis than patients on traditional formula. CONCLUSIONS: The new
available formula, with the characteristics of a thickened meal, is better than a
formula, traditionally thickened with added rice flour, in the conservative
treatment of infants with symptomatic gastrooesophageal reflux.
PMID- 9646216
TI - Gastrectomy, lack of gastric first pass metabolism of ethanol and alcoholic liver
disease. Results of a multicentre study.
AB - BACKGROUND: Some conditions characterized by a loss (anatomical or functional) of
parietal cells of the gastric antrum, containing an alcohol-dehydrogenase, may
reduce the first pass metabolism of ethanol at that level and, simultaneously,
raise its bioavailability. The observation that the first pass metabolism was
drastically suppressed after gastrectomy would appear to suggest that the latter
condition represents a risk for the development of liver damage in patients who
continue to consume alcohol even in a non relevant amount. METHODS: Consecutively
enrolled in the study were 304 individuals of both sexes aged between 45 and 70
years of whom 114 gastrectomized and 190 pair-matched control subjects all
submitted to an Upper Gastrointestinal Endoscopy for whatever disturbance. All
the patients were diagnosed as having liver disease with routine clinical and
instrumental means. Information was collected concerning the mean daily alcohol
intake, both before and after the operation. RESULTS: The overall prevalence of
hepatic lesions was shown to be higher in the gastrectomized than in the control
group (42.1% vs 25.8%, p = 0.005). Moreover, referring only to alcohol-related
hepatic lesions (steatosis, steato-fibrosis and cirrhosis), the prevalence was
higher in the gastrectomized patients than in the controls (29.8% vs 17.9%, p =
0.02). As far as concerns alcohol consumption, the gastrectomized group had
consumed 71 g/day and the control group 39 g/day alcohol per person (p < 0.05) in
a similar period of time (35 and 33 years, respectively). Also the non alcohol
related liver damage (especially the viral type) was slightly higher in the
gastrectomized patients (gastrectomized 12.3% vs control 7.9%, p = ns).
Accordingly, the percentage of serum markers of viral infection was higher in
this group (HBs Ag: gastrectomized 3.9% vs control 2.2%, p = ns; anti-HCV:
gastrectomized 13.5% vs control 5.0%, p = 0.03). Finally, to test the eventual
damaging effects of gastrectomy alone (excluding ethanol and/or viral infection),
two groups of patients with a medium to low alcoholic negative assumption (30-60
g ethanol/day) and no signs of viral infection (HBsAg and anti-HCV negative) were
extrapolated. In these two selected groups, the prevalence of alcoholic-related
hepatic lesions were not statistically different (28 gastrectomized 20.3% vs 44
control 18.4%). CONCLUSIONS: In conclusion, data emerging from investigations on
the population under study indicate that the alcohol and viral infection appear
to play a more important role in determining hepatic lesions than
gastroresection.
PMID- 9646217
TI - Ten-year incidence and natural history of gallstone disease in a rural population
of women in central Italy. The Rome Group for the Epidemiology and Prevention of
Cholelithiasis (GREPCO).
AB - AIMS: To investigate the incidence, risk factors and natural history of gallstone
disease, a random sample of females belonging to a rural population was enrolled
in a ten-year longitudinal study. METHODS: The study has been performed in a
small town on the hills south of Rome. In 1985, a random sample of 426 females,
aged 20-69 years, was screened by real-time ultrasonography for gallstones and
previous cholecystectomy. Screening methods included anthropometry, collection of
a blood sample and a questionnaire on the occurrence of abdominal symptoms.
During 1995, all these subjects were invited for a 10-year follow-up examination.
RESULTS: The overall 10-year incidence of gallstone disease was 6.3% (5.5% of new
gallstones and 0.8% of cholecystectomies). Only 23.1% of the women with
gallstones were aware of their condition. More than three quarters (76.9%) had
not suffered biliary pain. Univariate and multivariate analyses demonstrated a
positive independent association of new gallstone disease with body mass index
and parity. Out of the initially asymptomatic gallstone women, 15.4% experienced
at least one episode of biliary pain, 23.1% were submitted to elective
cholecystectomy and 61.5% remained asymptomatic. CONCLUSIONS: The study
demonstrates a high incidence of gallstone disease in women belonging to a rural
free-living population in Italy and suggests body mass index and parity as
possible true risk factors. Moreover, it confirms that a remarkable proportion of
asymptomatic patients become symptomatic and eventually undergo cholecystectomy.
PMID- 9646218
TI - Complete eradication of hepatitis C virus after interferon treatment for chronic
hepatitis C.
AB - BACKGROUND: Alpha-interferon therapy can lead to a persistent biochemical
response, but discordant opinions have been expressed on the definition of
sustained response and on the real possibility of complete eradication of
hepatitis C virus (HCV). AIMS: To define the clinical, virological and histologic
profiles of the patients with sustained response. PATIENTS: Twenty-eight patients
with three different biochemical and virological patterns of response to
interferon therapy (16 sustained responders, 6 responders with relapse and 6 non
responders) were studied for a follow-up period of 36 months. METHODS: HCV-RNA
sequences were investigated in serum, peripheral blood mononuclear cells and in
liver tissue by means of reverse transcriptase-polymerase chain reaction,
targeted to the 5' non coding region. Viral load in serum was quantified by
branched-DNA signal amplification. HCV genotypes were evaluated using a line
probe assay. RESULTS: All sustained responders showed persistent normal ALT
values and loss of serum HCV-RNA during the treatment and in the entire follow-up
period. The HCV clearance was also demonstrated in peripheral blood mononuclear
cells and in liver tissue. Pre-treatment HCV-RNA quantitation showed that
sustained responders had a significantly lower viral load compared to relapsers
and non responders (p = 0.005). HCV genotyping showed that patients infected by
genotypes 2a, 3a were more likely to achieve a sustained response. Interestingly,
a prolonged response was also observed in the only three patients with pre
treatment detectable viral load infected by genotype 3a and in patients with
genotype 1b and low viraemia levels. To assess the histologic outcome following
HCV eradication, all sustained responders underwent a second liver biopsy in the
follow-up period (6-18 months). Periportal necrosis and portal inflammation were
significantly improved. CONCLUSIONS: Our results suggest that persistent loss of
HCV-RNA in serum, peripheral blood mononuclear cells and liver as well as
histologic improvement are consistent with the complete HCV eradication even from
intracellular compartments and from potential extra-hepatic sites of viral
persistence. Moreover, pre-treatment viral load, HCV infecting genotypes and
histologic features may influence the clinical outcome of hepatitis C and the
response to interferon therapy.
PMID- 9646219
TI - Efficacy of oral ciprofloxacin as selective intestinal decontaminant in
cirrhosis.
AB - BACKGROUND: Selective intestinal decontamination has been proposed to prevent
bacterial infection in cirrhosis. AIMS: To evaluate the efficacy of ciprofloxacin
as selective intestinal decontaminant. PATIENTS AND METHODS: Quantitative
microbiological studies on serial faeces were carried out in 15 cirrhotic
patients. Ciprofloxacin was given orally at the starting dose of 250 mg every 12
hours for 7 days followed by a single dose of 250 mg/day from day 7 to day 14 and
125 mg/day for the next 3 weeks. Total stool samples were examined in basal
conditions and on days 7, 14, 21, 28 and 35 of treatment and 3 and 7 days after
treatment withdrawal. RESULTS: Gram-negative flora was completely eliminated in
all patients by ciprofloxacin given at doses of 500 and 250 mg/day. When the drug
was tapered to 125 mg/day, Escherichia coli reappeared in stools of 7 patients
(antibiotic-resistant in one patient) and Klebsiella oxytoca in two patients
(antibiotic-resistant in one patient). Faecal concentration of Group D
Streptococcus was significantly increased at the end of therapy (basal mean 7.7
+/- 1.2 log CFU vs post treatment mean 9.6 +/- 0.5 log CFU, p < 0.05) while the
faecal concentration of anaerobic flora and Candida albicans showed no change.
CONCLUSIONS: Results of this study demonstrate the efficacy of oral ciprofloxacin
as a selective intestinal decontaminant and ciprofloxacin 250 mg/day is the
recommended dose for maintaining Selective Intestinal Decontamination. However,
the risks of inducing antibiotic resistance in Gram-negative flora and promoting
overgrowth of Gram-positive flora must be carefully considered in all patients
chronically treated with oral quinolones.
PMID- 9646220
TI - Minimal change nephropathy presenting in a patient with primary sclerosing
cholangitis.
AB - The association of primary sclerosing cholangitis and renal disease is not
frequent, and is limited to a few reported cases of immune complex
glomerulonephritis. We report the case of a 34-year-old patient with sclerosing
cholangitis diagnosed 5 years earlier, with well preserved liver function and no
clinical manifestations of cholestasis, who developed minimal change nephropathy.
During the nephrotic phase of the disease, the peripheral blood lymphocyte count
was normal, with a relative increase in percent CD4+ and an increase in the CD4+:
CD8+ ratio. CD4+ cells showed immunoactivation. The HLA-DR expression on T-cells
was 59%, and 16.5% of CD3+ cells were CD25+. A course of prednisone therapy
induced long-lasting remission of the nephrotic syndrome. Peripheral blood
lymphocyte count and subtyping were normal 7 months after prednisone withdrawal.
We conclude that primary sclerosing cholangitis can be associated with minimal
change nephropathy; underlying cell-mediated immunity may be the common
pathogenic mechanism.
PMID- 9646221
TI - Ocular naevus and hyperaemia with dilation of the conjunctival vessels: an early
manifestation of Crohn's disease?
AB - Two cases of male patients with Crohn's disease showing the same neonatal ocular
abnormality, a sector hyperaemia with dilation of the vessels of the bulbar
conjunctiva surrounding a naevus close to the limbus, are presented. In both
cases, this manifestation worsened when Crohn's disease relapsed, and improved
when the disease went into remission with steroid treatment. In Crohn's disease,
eye involvement is reported in varying percentages, but the condition discussed
here does not fit into any of the ocular patterns previously described in this
disease, and could represent an early manifestation of Crohn's disease.
PMID- 9646222
TI - Polymerase chain reaction for the detection of HCV-RNA: cryoglobulinaemia as a
cause for false negative results.
AB - Polymerase chain reaction is widely used in clinical practice as a reliable assay
for the detection and quantitation of hepatitis C virus RNA in serum and tissue.
Due to the high sensitivity of the test, both false positive and false negative
results can occur. The presence of cryoglobulins in serum samples represents a
variable that can influence the result of a polymerase chain reaction assay
leading to false negative results. In cases of hepatitis C virus infection
associated with cryoglobulinaemia, it is extremely important to very carefully
process the samples to be tested in order to avoid cryoglobulin precipitation and
the consequent removal of the virus from the sample.
PMID- 9646223
TI - Liver targeting of nucleoside analogues coupled to galactosyl terminating
macromolecules: a new approach to the treatment of a chronic viral hepatitis.
AB - In order to reduce the extrahepatic side effects of antiviral nucleoside
analogues in the treatment of chronic viral hepatitis, these drugs are conjugated
with galactosyl-terminating macromolecules. The conjugates selectively enter
hepatocytes after interaction of the carrier galactose residues with a receptor
present in large amounts and high affinity only on these cells. Within
hepatocytes the conjugates are delivered to lysosomes where enzymes split the
bond between the carrier and the drug, allowing the latter to become concentrated
in the liver. The majority of experiments referred to in this paper were
performed employing a conjugate of lactosaminated human albumin with adenine
arabinoside monophosphate (ara-AMP), a phosphorylated nucleoside analogue active
against hepatitis B virus. This conjugate administered for 28 days to patients
with chronic hepatitis B exerted the same antiviral activity as that of the free
drug without producing any clinical side effects, including the severe
neurotoxicity caused by free ara-AMP. This result demonstrates the validity of
the liver targeting approach which enhances the therapeutic possibilities of
nucleoside analogues. Coupling to galactosyl terminating carriers may be a way of
obtaining higher drug concentrations within hepatocytes and permitting the use of
nucleoside analogues, the administration of which would otherwise be impossible
due to extrahepatic toxicity.
PMID- 9646224
TI - A ruptured hepatic artery aneurysm: combined percutaneous and endoscopic
management.
PMID- 9646225
TI - Pulmonary hypertension and hepatitis C virus related cirrhosis.
PMID- 9646226
TI - Ulcerative colitis in Greece: course and prognostic factors in 413 consecutive
patients.
PMID- 9646227
TI - Statistical evaluation of 2001 carcinoid cases with metastases, collected from
literature: a comparative study between ordinary carcinoids and atypical
varieties.
AB - This study aimed at obtaining a better understanding of the malignant
characteristics of carcinoids (gut endocrinomas) of the digestive system. After
excluding cases with no possible individual identification as for age and sex,
2001 carcinoid cases with metastases among 5647 of the digestive system
computerized in the Niigata Registry were thus subject to the present analysis.
These cases were divided into two groups: [A] 1719 with ordinary carcinoid
histology and [B] 282 with atypical varieties including argyrophil (endocrine)
cell carcinomas, small/oat cell carcinomas of endocrine type, composite carcinoid
adenocarcinoma varieties and other neuroendocrine tumors. In many aspects, a
comparative analysis demonstrated statistical differences between [A] and [B]:
average age (55.7 vs 60.1), the rates of metastases (34.4% vs 55.6%), the
association of carcinoid syndrome (21.4% vs 2.8%), tumor size 20mm or less (42.2%
vs 22.5%), depth of invasion down to the submucosa (21.6% vs 11.7%) and
transmural invasion (34.3% vs 47.7%), immunohistochemistry of neuron-specific
enolase (86.5% vs 66.7%), chromogranin (86.1% vs 67.6%), vasointestinal
polypeptides, ACTH and alpha-fetoprotein, and the 5-year survival rate (61.4% vs
17.9%). No statistical differences between these two groups were found in the
male to female ratio, serotonin activities and Grimelius argyrophilia. Although
no generally acceptable definite criteria and definition for atypical carcinoid
varieties have yet established, neoplasias of this category seem to have a wide
range of histological, histochemical, immunohistochemical, ultrastructural and
biochemical features that may mostly be placed in between ordinary carcinoids and
ordinary carcinomas.
PMID- 9646228
TI - Significance of vascular endothelial growth factor mRNA expression in invasion
and metastasis of hepatocellular carcinoma.
AB - Vascular endothelial growth factor (VEGF) is an important mediator of vascular
development in tumors. We aimed at clarifying the relationship between VEGF mRNA
expression and invasion or metastasis of hepatocellular carcinoma (HCC). Reverse
transcript-polymerase chain reaction (RT-PCR) was carried out on surgical
specimens of 48 patients with HCC. The relative levels of VEGF mRNA expression
were measured by determining a ratio between PCR products of VEGF and the
endogenous internal standard gene beta-actin. Expression of VEGF mRNA in tumor
was found in 76.5% (39/51) of patients, whereas it was 21.69% (11/51) in non
tumorous liver. The levels of VEGF mRNA expression in tumors with tumorous emboli
and in poor-encapsulated tumors were higher than that without tumorous emboli and
in well-encapsulated tumors respectively (p < 0.05 t test). There was no
significance in the expression of VEGF mRNA between large HCC (diameter > 5cm)
and small HCC (diameter < or = 5cm) (p > 0.05). VEGF may play an important role
in the invasion and metastasis of HCC. Angiogenesis in tumor correlates with
progression of HCC.
PMID- 9646229
TI - Assessment of methods for primary tissue culture of human breast epithelia.
AB - A serie of 29 human normal, benign and malignant breast tissues were cultivated
in an attempt to isolate and propagate primary breast epithelial cells in vitro.
Explants methodology as well as disaggregation techniques (enzymatic and
mechanical) were employed to obtain better culture conditions. Cells derived from
breast malignant tissue were propagated in an appropriate and survived in culture
for at least 6 months, exhibiting a marked preference to grow in suspension
(independent anchorage). Tumorigenicity assays in nude mice were performed with
malignant cells obtained from primary culture cells as well as with cells
achieved from successive passages. The rate of long time cell survival from
malignant and non-malignant tissues demonstrated the accuracy of the methodology
but it also emphasised the need for improving technology to obtain cell lines
with long survival.
PMID- 9646230
TI - Viruses in human oral cancers.
AB - The role of viruses in the etiology of human oral cancer is critically reviewed.
Available evidences show a positive correlation for human oral cancer with human
papilloma virus (HPV), herpes simplex virus (HSV) and human herpes virus type-6
(HHV-6), having strongest association with HPV. These viruses may act alone or in
combination with other carcinogens in the genesis of head and neck malignancies.
PMID- 9646231
TI - T-2 toxin affects proliferation of three different neoplastic cell lines.
AB - The antiproliferative effect of T-2 toxin (T-2) towards mouse melanoma B16 cells,
human myelogenous leukemia K562 cells, and human cervix carcinoma, HeLa cells,
was studied. For the first four days of T-2 presence B16 cell survival was
decreased in dose dependent fashion. However, cell survival after eleven days T-2
action may be dual: some stimulation of cell growth that was direct function of
the number of seeded cells per well was observed and cell survival (for the
highest number of seeded cells) six times greater than control, was noticed at 20
nM T-2 toxin concentration. A smaller cell growth stimulation (cell survival more
than 3 times higher than control) was observed with a lower cell number seeded
per well. Nevertheless, by eleventh day concentrations of T-2 higher than 35 nM
completely inhibited B16 cell proliferation. The same trend was noticed for T-2
action towards K562 cells. Treatment of HeLa cells with various T-2
concentrations led to a marked inhibition of cell survival that was more
pronounced at the end of 44th or 72nd hour, than after the 20th hour of agent's
action. ICs50 values obtained in the present work, suggest that B16 cells were
the most sensitive to T-2 antiproliferative action, while HeLa cells were the
most resistant. When PBMC were cultured with HeLa cells the antagonism against
various T-2 concentrations was observed; cell survival determined after 44, or 72
hours of cells incubation, was less decreased compared to cultures treated with T
2, or with PBMC only. In addition, it was shown that T-2 and cis-DDP had an
antagonist effect on HeLa cells survival.
PMID- 9646232
TI - Influence of tobacco on the labelling of red blood cells and plasma proteins with
technetium-99m.
AB - Technetium-99m-labelled red blood cells (RBC) have been used as
radiopharmaceutical in nuclear medicine. The influence of drug interaction in
this labelling process has been described along with the biological effects of
tobacco on the labelling of blood elements with technetium-99m. The labelling of
RBC and plasma proteins can be decreased in presence of tobacco. This can be due
to either a direct or indirect effect (reactive oxygen species) of tobacco by (i)
oxidation of the stannous ion, (ii) possible damages caused in plasma membrane
and/or (iii) possible chelating action on the stannous and/or pertechnetate ions.
PMID- 9646233
TI - Esophageal endocrinomas, an extremely rare tumor: a statistical comparative
evaluation of 28 ordinary carcinoids and 72 atypical variants.
AB - Esophageal endocrinomas are an extremely rare neoplasm. The present study aimed
to evaluate multiphasic clinical and pathologic aspects of 100 cases of
esophageal endocrinomas, consisting of 28 cases of ordinary type carcinoids and
72 atypical varieties collected from worldwide literature and recorded on
computer in the Niigata Registry. The evaluation of esophageal endocrinoma cases
was on most occasions carried out in accordance with a comparison between
ordinary carcinoids and atypical varieties. Esophageal endocrinomas were
generally characterized by a preponderance of male patients and an older age
group. They also exhibited a higher metastasis rate, and a lower incidence of
carcinoid syndrome than overall endocrinomas of the digestive series. They
further indicated a probable unfavorable postoperative outcome as compared to
endocrinomas in most other digestive organs. Ordinary carcinoids of the esophagus
were characterized by smaller size at detection, lower metastasis rate, and
better postoperative outcome than the atypical variety group. Because of the
extremely small number of cases of esophageal endocrinomas, additional case
reports are in future expected to be satisfactorily documented as a valuable
record.
PMID- 9646234
TI - Histopathological study of 110 cystectomy specimens for bladder cancer by an
original mapping method.
AB - The management of cystectomy specimens represents the first and most important
step in the study of bladder cancer and related lesions. We carried out a study
on 110 patients, applying an original mapping protocol which allowed to determine
the exact topography of lesions, recognizing even the smallest ones and putting
in evidence some rare histotype. A prevalence of high-grade, high-stage tumors
was noted, as well as a remarkable frequency of precancerous lesions, mostly
found in Brunn's nests. This latter finding could mean that in many cases a flat
carcinoma becomes invasive within a Brunn's nest rather than in surface
urothelium. We were also able to accurately evaluate prostatic pathology, finding
incidental malignant lesions of this gland in 24.2% of the cystectomized males.
The apparently worst prognosis of the patients who underwent chemotherapy depends
on the fact that they had grades and stages higher than the untreated subjects.
In conclusion, we believe that a more extensive sampling of cystectomy specimens
gives highly reliable prognostic data and represents an unreplaceable tool in
understanding bladder neoplasms.
PMID- 9646235
TI - Malignant oncocytoma of major salivary glands. Report of a post-irradiation case.
AB - The fourth case of malignant oncocytoma arising in the submandibular gland is
here reported. This tumor arose in a 48-year-old man after radiation exposure, a
finding never described before for malignant oncocytoma. In addition, several
regional metastatic lymph nodes were found. The diagnosis was confirmed by
histochemical and ultrastructural findings. The tumor cells showed easily
recognizable mucus production and, ultrastructurally, abundant mitochondria,
intracytoplasmic lumina lined by microvilli and lipid droplets. These last
features have only seldom been described in malignant oncocytoma. Furthermore,
the neoplastic cells were alpha-1-antitrypsin positive and S100, thyroglobulin,
carcinoembryonic antigen, and smooth muscle actin negative. A thorough review of
the literature is also presented.
PMID- 9646236
TI - Tropisetron in the prevention of acute nausea and vomiting in patients treated
with high dose epirubicin.
AB - Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3)
receptor, with proven efficacy in the control of emesis related to cancer
treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential.
This study was designed to determine whether a single intravenous administration
of tropisetron could prevent acute nausea and vomiting in patients treated with
high dose epirubicin. Forty chemotherapy naive breast cancer patients treated
with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in
the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand"
treatment with tropisetron 5 mg p.os was used for the rescue of patients who
failed on the initial i.v. dose. Complete control of acute nausea and vomiting
had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5%
(95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common
adverse event reported in 3 patients (7.5%) and constipation in 2 patients (5%).
Interestingly, patients with a negative experience of nausea and vomiting during
pregnancy and those treated for metastatic disease, had a better control of
chemotherapy-induced nausea and vomiting. In conclusion, a single 5 mg i.v. dose
of tropisetron is safe and effective in preventing acute emesis in patients
treated with high dose epirubicin.
PMID- 9646237
TI - Prognostic factors in renal cell carcinoma.
AB - In this study we evaluated some morphological and clinical prognostic factors in
166 patients with renal cell carcinoma (RCC). Patients' ages, sex and
localization of the tumor had no effect on survival. Tumor diameter and the
weight of the nephrectomy specimen revealed prognostic value. Stage of the tumor,
especially the presence of metastasis, is the most important prognostic factor
for RCC (p < 0.001). Tumor grade had prognostic value (p = 0.0146). The survival
difference between cell types was not significant (p > 0.05). Renal vein
invasion, the presence of pseudocapsules and tumor in the intravascular space,
mitotic rate, the presence and the number of lymphocytes and macrophages, along
with the presence of calcifications had no prognostic value (p > 0.05). The
presence of necrotic areas was significant (p = 0.0102). The patients with
"infiltrative growth pattern" showed poorer prognosis than patients with "pushing
type growth pattern", regardless of the existence of a pseudo capsule (p =
0.0045).
PMID- 9646238
TI - Recurrent cutaneous leiomyosarcoma.
AB - Cutaneous leiomyosarcoma is a rare tumour, accounting for 2.3% to 6.5% of all
soft tissue sarcomas. The case of a young patient with a cutaneous leiomyosarcoma
on the right gluteal region is here presented. The lesion misdiagnosed as a
keloid after primary excision of histiocytoma had a two-year history, had been
excised twice. The tumour was widely excised, and the wound closed primarily. No
recurrence or distant metastasis are reported 26 months after the initial
presentation. Clinical, histological, immunohistochemical features and surgical
strategies of the reported case are discussed and compared with literature.
PMID- 9646239
TI - Vulvar hemangiopericytoma. Case report.
AB - A rare case of a hemangiopericytoma of the vulva, observed in a 55-year old
woman, is presented. So far, only six cases of this uncommon disease--which
continues to be a source of uncertainty from both a prognostic and therapeutic
point of view--have been reported. The case is described along with a review of
international literature.
PMID- 9646240
TI - Primary scrotal malignant melanoma. Report of 2 cases and review of the
literature.
AB - Tumours involving the scrotum are rare and primary malignant melanoma is among
the rarest of these lesions. Between 1949 and 1996 only 7 cases have been
reported. We present two cases of scrotal melanoma. The current recommendations
and management strategies are discussed on the basis of a review of the
literature.
PMID- 9646241
TI - Papillary thyroid carcinoma: considerations on surgical treatment.
PMID- 9646242
TI - Unexpected thyroid cancer: clinical considerations and therapy.
PMID- 9646243
TI - Follicular thyroid lesions and risk of malignancy: a new diagnostic
classification on fine-needle aspiration cytology.
PMID- 9646244
TI - Immature malignant teratoma of the thyroid gland.
PMID- 9646245
TI - Diagnostic value of preoperative DNA measurement on FNA in benign and malignant
thyroid neoplasm.
PMID- 9646246
TI - Parathyroid functional assessment in patients following total thyroidectomy for
thyroid malignancies.
PMID- 9646247
TI - Flow chart for clinical staging of thyroid tumors.
PMID- 9646248
TI - Follicular neoplasms of the thyroid: diagnostic and operative management.
PMID- 9646249
TI - Papillary carcinoma in small hypoechoic thyroid nodules: predictive value of echo
color Doppler evaluation. Preliminary results.
PMID- 9646250
TI - Mixed squamous and small cell lung carcinoma with separate histologic subtypes in
eye and phalanx metastases.
PMID- 9646252
TI - Procedures for the diagnosis of virus particles by electron microscopy.
PMID- 9646251
TI - Preoperative identification of benign versus malignant thyroid nodules, salivary
glands nodule and enlarged lymph nodes: preliminary results of a modified fine
needle biopsy technique.
PMID- 9646253
TI - Genetic markers in the blood of animals: a historical review.
AB - In this review an attempt is made to list the most important events in the search
for genetic markers in the blood of animals. In chronological order, blood
groups, biochemical polymorphisms, lymphocyte antigens and DNA markers have been
discovered and used in practice. Of all practical uses, parentage verification
and exclusion are regarded as the most important, and it can be said with pride
that the South African Stud Book is as infallible as any other stud book in the
world.
PMID- 9646254
TI - The effect of endotoxin and anti-endotoxin serum on synovial fluid parameters in
the horse.
PMID- 9646255
TI - Targeted radiotherapy with Sm-153-EDTMP in nine cases of canine primary bone
tumours.
AB - Nine dogs with primary bone tumours were treated with Samarium-153-EDTMP (Sm-153
EDTMP). Conventional treatment protocols were precluded by the size of the dogs
and the owners' refusal of limb amputation. All the tumours were of the
appendicular skeleton; 4 were confirmed osteosarcomas. The other 5 tumours were
radiologically suspect for osteosarcoma. Bone scans were performed on all dogs
using Technetium-99m-methylene diphosphonate (Tc-99m-MDP) before administration
of Sm-153-EDTMP. Regions of interest were identified over the contralateral limb
at the same site as the tumour and counts per pixel were recorded for the tumour
and contralateral limb and expressed as a ratio. The dogs were given 1 injection
of 37 MBq/kg (1 mCi/kg) of Sm-153-EDTMP intravenously. Thoracic and primary
tumour site radiographs were taken at monthly or 2-monthly intervals to monitor
progression of the primary tumour and search for evidence of metastasis. Two dogs
showed no response to treatment, with an increase in bone pain, and were
euthanased within 1 month. In 1 dog, a tumour of the scapula underwent complete
involution and the dog is considered free of disease at 20 months post Sm-153
EDTMP treatment. The overall tumourcidal effect of a single dose of Sm-153-EDTMP
on primary bone tumours was difficult to evaluate in this group of dogs, as, with
one exception, all the primary tumours progressed over time and the dogs were
euthanased. Pain control, for which Sm-155-EDTMP is used in man, was not evident,
except in the dog that responded completely to treatment.
PMID- 9646256
TI - Stability of cardiodynamic and some blood parameters in the baboon following
intravenous anaesthesia with ketamine and diazepam.
AB - The stability of cardiodynamic and some blood parameters during a slow,
continuous infusion of a combination of ketamine and diazepam is reported.
Contractility (dP/dt), myocardial relaxation (Tln), left ventricular end
diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), arterial
blood pressure and certain blood parameters were assessed in 3 male and 3 female
juvenile baboons (Papio ursinus). Anaesthesia was induced with 15 mg/kg ketamine
i.m. and maintained with a continuous i.v. infusion (40-60 ml/h) of ketamine and
diazepam. The mixture consisted of 2 ml ketamine (100 mg/ml), 2 ml diazepam (5
mg/ml) and 50 ml saline. A period of 75 +/- 10 min was allowed for preparation of
the animals, after which lead II of the ECG, femoral artery blood pressure and
left ventricular pressure were recorded at 15-min intervals for a period of 2 h:
the total duration of anaesthesia was 195 min. Arterial blood samples were
analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin.
Left ventricular parameters were derived from the left ventricular pressure
curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p
< 0.037) at the 195-min interval. No arrhythmias or ECG changes were seen, while
blood pressure decreased gradually. Serum calcium concentration decreased and
blood glucose levels increased gradually over time. Anaesthesia and analgesia
were sufficient and no other drugs were necessary. The animals appeared sedated
and dazed 60-80 min after the procedure. A continuous infusion of a combination
of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia
for cardiodynamic measurements.
PMID- 9646257
TI - Psychogenic alopecia in a cat: response to clomipramine.
PMID- 9646258
TI - Osteitis of the apex of the third phalanx following foot trimming in a dairy cow.
AB - An adult Ayrshire cow was presented with bilateral hind-limb lameness 5 weeks
after routine claw trimming. Examination under intravenous regional anaesthesia
revealed ulceration of the sole at the toe of both the right lateral and left
medial claws of the hind limbs. Radiographic examination showed osteolysis and
pathological fractures of the 3rd phalanx of both affected claws. Wooden blocks
were fixed to the 2 healthy claws and the bone fragments were removed using a
different technique for each claw. Full recovery followed within 11 weeks. The
aetiological factors and treatment options for this condition, which was
considered to be caused primarily by incorrect claw trimming, are discussed.
PMID- 9646259
TI - Datura seed intoxication in two horses.
AB - A sunflower-based feed supplement grossly contaminated with the seed of a Datura
sp. resulted in severe signs of poisoning in 2 horses. One horse died peracutely
of acute gastric dilatation and rupture following ingestion of the contaminated
feed. The 2nd horse developed unresponsive paralytic ileus that led to
euthanasia. Examination of the feed and gastrointestinal contents of both horses
showed a high proportion of the characteristic Datura sp. seeds. The clinical
signs and pathology in both cases were consistent with intoxication by the
parasympatholytic alkaloid components of Datura sp.
PMID- 9646260
TI - Acute Lantana camara poisoning in a Boer goat kid.
AB - Acute Lantana camara poisoning in a Boer goat kid is described. The animal was
part of a flock of boer goats that was introduced from the Kalahari thornveld,
where the plant does not occur, to an area where the plant grew abundantly. At
necropsy, the animal was severely icteric, dehydrated and constipated, with
hepatosis, distention of the gall-bladder and nephrosis, but no skin lesions.
Histopathological findings of the liver confirmed moderate hepatosis with single
cell necrosis and bile stasis. The pathology is consistent with that described in
acute Lantana poisoning in cattle, sheep and goats. The absence of
photosensitisation may be attributed to relatively mild liver damage, or the
rapid course of this toxicosis.
PMID- 9646261
TI - Hyperreninaemic hypoaldosteronism in a dog.
AB - A 9-year-old male German shepherd dog was evaluated for clinical and clinico
pathological changes that were suggestive of Addison's disease. On further
investigation the basal plasma cortisol concentration was high, a normal cortisol
response to ACTH stimulation occurred, plasma renin activity was elevated and low
serum aldosterone concentration was present. A diagnosis of hyperreninaemic
hypoaldosteronism was made. Replacement fludrocortisone resulted in complete
normalisation of the electrolyte and fluid imbalances. Hyperreninaemic
hypoaldosteronism has never been reported in the dog.
PMID- 9646264
TI - [Efficiency of investigators in recruitment of patients for clinical trials:
apropos of a multinational study].
AB - BACKGROUND: Performance and efficiency in patient selection are essential for
conducting clinical trials. Data on these are presented from a multinational
trial. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled,
parallel-group study in asthma, with a screening phase followed after
randomization by a treatment period, was selected. Number of patients screened
and randomized by centre and country, centres achieving the minimum recruitment
(> or = 10 patients randomized), and efficiency of investigators
(randomized/screened x 100) were determined and compared. RESULTS: 564 patients,
out of 836 screened, were randomized at 69 centres in 11 countries. Twenty-four
centres (35%) randomized > or = 10 patients each, accounting for 70% (n = 395) of
the total number recruited. Efficiency was significantly higher among these "high
performance" centres (81.4%; p < 0.001; OR, 4.7; CI 95%, 3.4-6.5) than in the
remaining ones (48.1%). Five countries had > or = 2 "high-performance" centres.
Efficiency was also significantly higher (p < 0.001) among those (370
randomized/455 screened, 82.1%) than in the remaining centres of the same
countries (82/140; 58.6%; OR, 3.0; CI 95%, 2.7-4.7). A relevant number of centres
(n = 17; 25%) randomized 0-1 patient (7 randomized/58 screened). CONCLUSION: The
analysis of patient selection in clinical trials showed that a minority of
centres accounted for most of the patients recruited. Those are not only the most
productive (more patients randomized) but also the more efficient (better quality
of screening process).
PMID- 9646265
TI - [Subtyping panic disorders according to their symptoms].
AB - BACKGROUND: Panic disorder (PD) is a common illness associated with high levels
of disability and with a high utilisation of non-psychiatric health services
which is inefficient in most cases. A better understanding of the clinical
subtyping of PD may improve diagnosis both in psychiatric and medical settings.
The present study is aimed at assessing the frequency, factorial grouping and
comorbidity of PD symptoms in a naturalistic sample of patients. PATIENTS AND
METHODS: All consecutive cases of PD (n = 442) who contacted with two outpatient
clinics in Barcelona (Spain) were assessed by two experienced interviewers.
Assessment instrument included SCID-UP-R interview and inventory of panic
symptoms based on DSM-III-R. RESULTS: Palpitations (86.7%), shortness of breath
(76.5%), fear of dying (69.9%) and dizziness (63.6%) were the most frequent and
intense symptoms reported by the PD patients. The principal component analysis
revealed four factors which explained the 56% of the variancel
"cardiorespiratory" (23.2%), "depersonalization-derealization" (15.8%),
"vestibular" (10%) and "mixed" (7%). CONCLUSIONS: The frequency of presentation
of symptoms was similar to other studies. However some disimilarities appeared
that may be attributed to transcultural differences as well as terminological
problems and the range of symptoms assessed. Factors found in the present study
support the clinical subtyping of PD in 3 groups characterised by
cardiorespiratory symptoms and fear of dying, cognitive symptoms
(depersonalization-derealization) and vestibular symptoms such as dizziness and
faintness.
PMID- 9646266
TI - [Interrelationship between the duration of HIV infection, viral load and CD4
positive lymphocyte count].
AB - BACKGROUND: The decline in CD4+ lymphocytes occurs at different rates in patients
with HIV infection. A longer duration of HIV infection and a higher level of
viral replication, represented by the viral load, are associated with a lower
CD4+ lymphocyte count. However, the interelationship between these variables is
still not well known. PATIENTS AND METHODS: 107 HIV-infected patients for whom
the date of infection was known, were included in a transversal study, in which
the CD4+ lymphocyte count and the plasma viral load were analysed, the last using
an isothermal amplification method (NASBA). Patients were not receiving
antiretroviral drugs or suffered intercurrent infections at the time of the
study. RESULTS: The mean duration of HIV infection was 8.6 +/- 2.9 years. The
mean CD4+ lymphocyte count was 366 +/- 264 x 10(6)/l. The mean plasma viraemia
was 4.3 +/- 0.9 logs. In a linear regression model, the CD4+ lymphocyte count was
explained in 21.7% of cases by the duration of HIV infection, meanwhile the viral
load justified up to 36.2 of CD4+ cell variability. When both parameters were
combined, up to 58.4% of CD4+ lymphocyte values were explained. In this model,
changes of 1 log in viral load had a 4-fold higher effect on the CD4+ cell count
than each year of HIV infection. CONCLUSIONS: The duration of HIV infection and,
particularly the viral load strongly influences the current CD4+ lymphocyte
count, although other variables should exist (virus with syncytium-inducing
phenotype, age of the patient and his immunegenetic repertoire) influencing the
different decline seen in CD4+ T-cells.
PMID- 9646267
TI - [Menopause and musculoskeletal manifestations. Is there a relationship?].
PMID- 9646268
TI - [The neonate and nosocomial infection].
PMID- 9646270
TI - [Hospital libraries in Spain and the need for information by health care
professionals].
PMID- 9646269
TI - [Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of
dystrophin associated protein complex].
AB - Linkage studies have confirmed the existence of clinical an genetic heterogeneity
among the muscular dystrophies due to adhalin deficiency. We present the
clinical, histological and genetic characteristics in a case of primary
adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19
years-old woman, born of non consanguineous parents, who shows a long evolution
myopathy with onset before age 7, a severe evolution and becoming wheelchair
bound at 10 years. She showed evident calf pseudohypertrophy and serum
creatinkinase (CK) levels were elevated (40-180 times the standard level). The
histological pattern showed a destructed fascicular architecture in agreement
with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal
antibodies and abnormal staining pattern with anti-adhalin antibodies. The
molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77
of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan
complex localised in chromosome 17. In the light of this case, we suggest a
revision of the diagnostic orientation in the muscular dystrophies and we review
the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical
signs which could indicate a given genetic locus.
PMID- 9646271
TI - [Perverted authorship].
PMID- 9646272
TI - [Evaluation of quality of life in clinical trials].
PMID- 9646273
TI - [Abuse of the emergency departments by patients. Are there immediate solutions?].
PMID- 9646274
TI - [Estimation of the prevalence of depression from the daily defined doses of
antidepressive drugs].
PMID- 9646275
TI - [Bioavailability of medications].
PMID- 9646276
TI - [Hydroxycobalamin in the treatment of poisoning by both carbon monoxide and
cyanide].
PMID- 9646277
TI - [Limb shaking syndrome triggered by severe anemia in a patient with dissection of
the internal carotid artery].
PMID- 9646278
TI - Effects of newly synthesized amino acids containing thiazole residues on
electrically evoked smooth muscle contractions.
AB - New amino acids containing thiazole residues have been synthesized and in vitro
experiments were performed to study their action on neurotransmission in target
tissues with adrenergic and cholinergic neurotransmission. Acetaminothiazoles,
structurally related to the novel class, are known to act as H1 agonists,
therefore, the effects of the newly synthesized Ala- and Pro-thiazole derivatives
on smooth muscle contractile activity were compared to those of histamine (HA).
The experiments were carried out on electrically stimulated prostatic part of rat
and rabbit vasa deferentia and proximal guinea pig ileum. HA had biphasic effect
on electrically evoked neurogenic contractions of guinea pig ileum, Pro(Thz) had
a stimulating effect, while Ala(Thz) had no effect. The histamine H1-receptor
antagonist diphenhydramine inhibited the Pro(Thz)-induced spontaneous contractile
activity in the longitudinal layer of guinea pig ileum. HA had a biphasic effect
on electrically induced neurogenic contractions of rat and rabbit vasa deferentia
while Pro(Thz) and Ala(Thz) inhibited the ES-contractions. The present results
show that the newly synthesized compounds might affect the electrically evoked
smooth muscle contractions. Some similarity in the effects of HA and of the new
substances was observed.
PMID- 9646279
TI - Clonidine and vasomotion physiology.
AB - It is known that clonidine exerts a hyperpolarizing action and alpha 2-adrenergic
activity. The experimental work investigates the conditions under which each
action of clonidine is developed on vascular smooth muscle. Two parameters were
studied in vitro on bovine aortic media, Ca2+ uptake and vascular tone. The Ca2+
uptake measurement was performed by incubating in Krebs' solution small slices of
the preparation in the presence of 45Ca. Studies on vascular tone were performed
on deendothelialized bovine aortic rings suspended in Krebs' solution. Low
concentrations of clonidine (1 nM-1 microM) decrease Ca2+ uptake and relax the
preparation, indicating dominance of the inhibiting action of clonidine may be
due to an hyperpolarization. Clonidine 10 microM results in equalization of the
opposing actions of Ca2+ uptake and vascular tone. When the preparation is
stimulated by alpha 1-adrenergic against phenylephrine 1 microM, clonidine 1 nM
10 microM potentates the Ca2+ uptake and vascular contraction in a monophasic
way, indicating that the depolarizing mechanisms connected with the alpha 1
adrenergic stimulation totally inhibit the relaxing action of clonidine possibly
due to hyperpolarization. This action is restricted in the presence of yohimbine
(alpha 2-adrenergic blocker).
PMID- 9646280
TI - In vivo antiinfluenza virus activity of Kampo medicine Sho-seiryu-to through
mucosal immune system.
AB - The Kampo (Japanese herbal) medicine, Sho-seiryu-to, which has traditionally been
used for the treatment of colds and bronchial asthma, showed potent antiinfluenza
A and B virus activity through augmentation of production of antiviral IgA
antibody in the nasal and bronchoalveolar cavities of mice when administrated
orally before viral infection. Sho-seiryu-to also showed antiinfluenza virus
activity against A virus H1N1 subtype infected in aged mice (approximately 6
months old) with an increase of antiviral IgA antibody in the bronchoalveolar
wash of the treated mice by similar administration. When mice infected with mouse
nonadapted influenza A virus H3N2 subtype before 14 days were secondarily
infected with mouse adapted A/PR/8 (H1N1) virus and administered Sho-seiryu-to
orally after the second infection, replication of the virus in both nasal and
bronchoalveolar cavities was significantly inhibited. Sho-seiryu-to had no effect
on the mice which were not primed with mouse nonadapted virus when administered
after the infection of mouse-adapted A/PR/8 virus. Oral administration of Sho
seiryu-to caused increment of viral-specific IgA antibody secreting cells in
mouse nasal lymphocyte. Sho-seiryu-to also augmented IL-2 receptor beta chain+ T
cells in Peyer's patch of the infected mice. Sho-seiryu-to also significantly
reduced viral titer in the nasal washes of the infected ovalbumin-sensitized
bronchial asthma model mice. Oral administration of Sho-seiryu-to before and
after vaccination significantly augmented hemagglutination-inhibiting antibody in
the serum by nasal inoculation of influenza HA vaccine, and significantly
augmented nasal antiviral IgA antibody and bronchoalveolar and serum antiviral
IgG antibodies even after secondary vaccination although induction of antiviral
antibody by intranasal vaccination was insufficient without Sho-seiryu-to. These
results suggest that Sho-seiryu-to is able to prevent influenza virus infection
by cross-protection of subtypes of influenza A virus and B virus. Sho-seiryu-to
is also useful for the treatment of influenza virus infection in hosts with a
history of influenza virus infection and/or influenza vaccination and allergic
pulmonary inflammation, such as bronchial asthma, and can be used as an adjuvant
to nasally inoculated influenza HA vaccine.
PMID- 9646281
TI - Comparison of effect of [D-Arg2,Sar4]-dermorphin (1-4) and morphine on mouse
small intestinal transit and electrically evoked contraction of guinea pig ileum.
AB - [D-Arg2,Sar4]-dermorphin (1-4) [DAS-DER (1-4)] was compared with morphine for the
capacity to affect mouse gastrointestinal transit and electrically evoked
contractions of the guinea pig ileum (GPI). A single subcutaneous injection with
DAS-DER (1-4) and morphine dose-dependently inhibited gastrointestinal transit of
charcoal in mice. DAS-DER (1-4) with ID50 of 0.053 mg/kg was 26 times more potent
than morphine with ID50 of 1.38 mg/kg. The inhibitory effects of DAS-DER (1-4)
and morphine were completely inhibited by pretreatment with 1 mg/kg naloxone, an
opioid receptor antagonist. The GPI contraction was inhibited by DAS-DER (1-4)
with an IC50 of 6.9 +/- 0.7 nM and morphine with an IC50 of 295.0 +/- 11.8 nM,
respectively. These effects were also inhibited by preincubation with naloxone.
Repeated subcutaneous injections of DAS-DER (1-4) and morphine to guinea pigs
produced tolerance to the inhibitory effect on electrically evoked contractions
of GPI. Moreover, a marked cross tolerance was seen in guinea pigs made tolerant
to DAS-DER (1-4) or morphine. The present study indicates that pharmacological
profiles of DAS-DER (1-4) as assayed by the gastrointestinal transit and
stimulated contractions of the GPI were almost similar to that of morphine.
PMID- 9646282
TI - General pharmacological profile and effects of E-4716, a novel histamine receptor
blocker, on the central nervous system.
AB - The general pharmacological profile and effects of E-4716 on the CNS have been
investigated in comparison with other histamine receptor blockers. In in vitro
studies with isolated organs and in binding studies on numerous receptors, E-4716
had no activity even at high concentrations, except for the selective blockade of
H1 receptors. No activity was observed in pharmacological trials in vivo, such as
the Irwin test or analgesia induced by phenylbenzoquinone or electroshock,
suggesting a depressant activity on the CNS. In tests potentiating hypnosis
induced by barbiturates, benzodiazepines and ethanol in mice, E-4716 always
showed milder potentiating effects than the other reference drugs. In monkeys, no
sedating effects were observed at 200 mg/kg, p.o. These results suggest that E
4716 exhibits good clinical efficacy without any secondary effects.
PMID- 9646283
TI - Micronization: a method of improving the bioavailability of poorly soluble drugs.
AB - For poorly soluble drugs, the digestive absorption depends on their rate of
dissolution. Decreasing the particle size of these drugs improves their rate of
dissolution. Fine grinding mills are use to micronize powders: either jar mills
or fluid energy mills. Theses processes were applied to griseofulvin,
progesterone, spironolactone and diosmin. For each drug, micronization improved
their digestive absorption, and consequently their bioavailability and clinical
efficacy.
PMID- 9646284
TI - Pharmacokinetics of factor VIII in hemophilia A patients assessed by frequency
response method.
AB - The frequency response method, having its mathematical underpinnings in the
theory of linear dynamic systems, was utilized to model pharmacokinetic systems
describing the fate of factor VIII (F VIII) administered to hemophilia A patients
before surgery. The pharmacokinetic system was defined on the basis of the
patient's data in such a way that the injection of F VIII during 5-15 min was
considered the input, and the corresponding plasma F VIII concentration profile
consisting of both the injection and post-injection part the output of this
system. The approach is an alternative to routine procedures based only on
evaluation of the post-injection part of the F VIII concentration profile. With
respect to the common sampling schedule of F VIII, simple second-order models
were found acceptable for all the patients involved in the study. However, in the
patients whose plasma F VIII concentration profiles did not decrease monotonously
after the injection, these models failed to approximate secondary peaks
indicating the presence of time delays in F VIII kinetics. The results obtained
were discussed with respect to applications of pharmacokinetic models for the
adjusted dose continuous infusion of F VIII in hemophilia A patients during and
after surgical interventions.
PMID- 9646285
TI - Basic and clinical studies on the measurement of tau protein in cerebrospinal
fluid as a biological marker for Alzheimer's disease and related disorders:
multicenter study in Japan.
AB - The development of a diagnostic marker for earlier and more accurate clinical
diagnosis of Alzheimer's disease (AD) is essential to identify AD patients during
life unequivocally. The purpose of this study was to investigate the basic
performance and clinical significance of tau level measurement in the
cerebrospinal fluid (CSF) using an enzyme-linked immunosorbent assay (ELISA)
developed by Innogenetics. The ELISA system showed reliable reproducibility and
good linearity. For clinical studies, the CSF samples from a variety of patients
(n = 332) were examined. They were classified into the four groups: Alzheimer's
disease (AD); neurodegenerative disease (ND); cerebrovascular diseases (VD); and
a neurological control (NC) group. The CSF-tau levels for AD, ND, VD and NC were
426 +/- 234 pg/ml, 239 +/- 157 pg/ml, 216 +/- 136 pg/ml, and 188 +/- 103 pg/ml,
respectively. The CSF-tau level of the AD group was significantly higher than
that of the other groups (p < 0.001). The CSF-tau levels increased during follow
up. The measurement of the tau level in CSF is shown to be a useful marker to
confirm a clinical diagnosis of AD.
PMID- 9646286
TI - Behavioral pharmacology of melatonin.
PMID- 9646287
TI - Preclinical and clinical behavioral paradigms for testing drugs that affect
learning and memory processes.
PMID- 9646288
TI - Effects of zinc and nutritional status on clinical outcomes in head and neck
cancer.
AB - The head and neck cancer patient often presents with both protein malnutrition
and trace element deficiencies. Zinc has been found to be deficient in many head
and neck cancer patients. In this study, pretreatment zinc status and nutritional
status (measured by the Prognostic Nutritional Index [PNI]) were correlated with
clinical outcomes in 47 patients. The patients were followed-up for a median of
52 mo from the time of enrollment. Our results showed that the tumor size and
overall stage correlated significantly to zinc status whereas no such correlation
was seen with PNI, alcohol intake, or smoking in our subjects. The results also
showed that impaired zinc status was associated with an increased number of
treatment morbidities, unplanned hospitalizations, and treatment delays (P <
0.05). Nutritional status was not associated with any studied outcome variable.
The disease-free interval was highest for the group which had both zinc
sufficient and nutrition-sufficient status. Although our data do not prove
conclusively, they do suggest that impaired zinc status at presentation may
contribute to treatment morbidity, and that for an optimal mean disease-free
interval, a sufficient zinc and nutritional status is required.
PMID- 9646289
TI - Experimental infusion phlebitis: tolerance osmolality of peripheral venous
endothelial cells.
AB - This study aimed to determine the osmolality that peripheral venous endothelial
cells can tolerate and to clarify the relationship between tolerance osmolality
and duration of infusion. Nutrient solutions of 539-917 mOsm/kg, prepared to have
no acidic effect, were infused into rabbit ear veins, and the veins were examined
histopathologically. In each experiment of 8-, 12-, or 24-h infusion, the higher
osmolality solutions caused some phlebitic changes, such as loss of venous
endothelial cells, inflammatory cell infiltration, and edema; however, the lowest
osmolality solution caused few changes. Infusion of 120 mL/kg of 814 mOsm/kg
solution caused phlebitis at 5 or 10 mL.kg-1.h-1, however, the same volume of the
same solution scarcely caused phlebitis at 15 mL.kg-1.h-1 because of the
shortened infusion duration. These results suggest that the tolerance osmolality
of peripheral venous endothelial cells with poor blood flow is about 820 mOsm/kg
for 8 h, 690 mOsm/kg for 12 h, and 550 mOsm/kg for 24 h, and that the tolerance
osmolality falls as the duration of infusion increases. In conclusion, hypertonic
solutions should be infused at as high a rate as is clinically acceptable and
compatible with nutrient bioavailability because increasing the infusion rate
reduces the duration of infusion and phlebitis.
PMID- 9646290
TI - Reduction of gut hypoplasia and cachexia in tumor-bearing rats maintained on
total parenteral nutrition and treated with peptide YY and clenbuterol.
AB - Prevention of gut hypoplasia associated with total parenteral nutrition (TPN) was
investigated in 67 adult male Fisher 344 rats. Mass and protein content of the
small intestine was reduced by 31% and 39%, respectively, after 7 d of TPN in
tumor-bearing (TB) rats. Coinfusing peptide YY (PYY; 1 nmol.kg-1.h-1) and
treating the rats with the anabolic beta-adrenergic agonist, clenbuterol (CLE; 2
mg.kg-1.d-1), resulted in significant savings in small intestine weight (26%
increase) and protein (42% increase). Although the colon also exhibited a
significant decrease in mass (31%), none of the treatment combinations were
effective in this region of the gut. Histologic analysis of ileum suggested that
the additive effects of PYY and CLE were due to differential effects of these
compounds on mucosal and muscular tissues, respectively. This combination of
treatments also resulted in significant savings (30% increase) in gastrocnemius
protein, suggesting a reduction in the cachectic response. These results suggest
that TPN-induced gut hypoplasia and cancer cachexia may be reduced by the proper
combination of nutritional, hormonal, and pharmacologic treatments. In addition,
the anabolic effects of various treatments may be additive to counteract TPN
induced gut atrophy.
PMID- 9646291
TI - Intestinal adaptation in short bowel syndrome without tube feeding or home
parenteral nutrition: report of four consecutive cases.
AB - Because home total parenteral nutrition (TPN) is not available to most of the
Brazilian population, an alternative treatment for short bowel syndrome was
evaluated. Four patients ages 40-65 y (mean: 53.75 +/- 10.59), three with
mesenteric thrombosis, and one with Crohn's disease were studied. The average
length of the remaining small bowel in these patients was 54.5 +/- 6.4 cm; the
ileocecal valve was preserved in 3 cases. A progressive step diet was used for
intestinal adaptation. Administration of pectin was started at the beginning of
the special oral diet (step 1), followed by medium-chain triacylglycerols (MCTs)
and complex, nonfermentable sugars (step 2); coconut oil (47% MCTs) and simple
sugars (step 3); and long-chain triacylglycerols and lactose (step 4). TPN was
interrupted at step 3 or 4 when the energy content of the diet reached 150% of
the patient's resting energy expenditure, if serum albumin and weight were stable
or increasing, and if the frequency, amount, and consistency of stools remained
unchanged. Nutritional follow-up showed that patients responded well to this
approach; also, patients returned to their previous professional activities.
Thus, enteral formulas were not essential for gastrointestinal adaptation. Home
TPN should not be indicated on the basis of strict criteria, but rather when a
patient fails to adapt to a progressive, special oral diet.
PMID- 9646292
TI - The potential role of antioxidant vitamins in preventing cardiovascular diseases
and cancers.
AB - Cardiovascular diseases and cancers constitute major public health problems in
all industrialized countries, where they are the main causes of premature
mortality. There is a large body of evidence suggesting that free-radical
production can directly or indirectly play a major role in cellular processes
implicated in atherosclerosis and carcinogenesis. Here we present mechanistic
data and results of epidemiologic studies on the relationship between antioxidant
vitamin intake or biochemical status and the risk of cancer and cardiovascular
diseases. Most epidemiologic data obtained on this topic were based on an
observational approach, i.e., ecologic, case-control, or prospective studies. All
these studies indicate that a high dietary intake or high blood concentrations of
antioxidant vitamins are associated with a reduced risk of cardiovascular
diseases and cancer at several common sites. Although the results of these
studies are convergent, they merely suggest a relationship at the population and
individual level but do not affirm a causality link. Only intervention studies
(randomized trials), by specifically changing antioxidant vitamin intake, can
provide conclusive answers. The apparent discrepancies between the results of
four recently published trials may be explained by the type of population
(general or high-risk subjects), the differing doses of supplementation
(nutritional levels or higher), the number of antioxidants tested (one, two, or
more), and the type of administration (alone or in balanced association). It thus
appears that a low risk of pathologies may be related to multiple nutrients
consumed at nutritional doses and in combination. Optimal effects may be expected
with a combination of nutrients at levels similar to those found in a healthy
diet. A single antioxidant vitamin given at high doses in subjects with high risk
of pathologies (smokers, asbestos-exposed subjects) may not have substantial
benefits and could even have negative consequences.
PMID- 9646293
TI - Control of postprandial intestinal motility.
PMID- 9646294
TI - Aging mechanisms from nematodes to mammals.
PMID- 9646296
TI - Dietary interventions in noninsulin-dependent diabetes mellitus: new approaches.
PMID- 9646295
TI - Roles of amylin in diabetes and in regulation of nutrient load.
AB - In summary, amylin, via its hormonal actions, may be relevant to the treatment of
both forms of diabetes, and, paradoxically, via its amyloidogenic properties, may
also be relevant to the pathogenesis of NIDDM. Amylin potently inhibits
postprandial glucagon secretion. The absence of this action could contribute to
the hyperglucagonemia and subsequently, excessive endogenous glucose production,
fasting hyperglycemia, and propensity to ketosis seen in insulinopenic diabetes.
Restoration of normal glucagon secretion by amylin replacement therapy could
therefore be therapeutically important in treatment of insulin-dependent diabetes
mellitus. Amylin potently inhibits gastric emptying. This action is consistent
with a physiologic role of amylin to regulate carbohydrate absorption. Of
peptides known to be secreted in response to ingested carbohydrate, only amylin
and glucagon-like peptide-1 are reported to inhibit gastric emptying at near
physiologic concentrations, and could therefore participate in nutrient-mediated
feedback control of carbohydrate release from the stomach. Amylin reduces food
intake in rodents. This action, which synergizes with a similar action of CCK,
could reflect a role as short-term peripheral satiety agent. Amylin alone or in
combination with CCK may be useful in moderating caloric intake in obesity and
other metabolic disorders. Although insulin has been extensively studied as a
therapy and as a controller of nutrient storage and metabolism, the role of its
beta-cell partner, amylin, has been largely unrecognized. In contrast to the
nutrient disposal and storage role of insulin, amylin appears to more generally
address the opposite side of the energy balance equation, the assimilation of
nutrient.
PMID- 9646297
TI - Use of a reduced-carbohydrate, modified-fat enteral formula for improving
metabolic control and clinical outcomes in long-term care residents with type 2
diabetes: results of a pilot trial.
AB - Physiologic responses of 30 enterally-fed long-term care residents with type 2
diabetes receiving total nutrition support via either a disease-specific (reduced
carbohydrate, modified-fat) formula or a standard high-carbohydrate formula for 3
mo were compared. Objectives of the study included evaluating metabolic response
(glycemic control and lipids) and clinical outcomes. Thirty-four subjects
requiring total enteral nutrition support by tube were enrolled in this
prospectively randomized, double-blind, controlled, parallel group 3-mo pilot
trial. Thirty were evaluable in that they completed 4 wk. Twenty-seven completed
all 12 wk. The groups were well-matched for physiologic and demographic
parameters at baseline. Fasting serum glucose and capillary (fingerstick) glucose
values demonstrated better control in the disease-specific formula-fed group.
Serum lipid profiles of this group were similar to or better than those of the
standard formula-fed group. The amount of insulin administered to insulin-using
subjects in the disease-specific formula-fed group was consistently less than
before initiation of the formula, whereas the amount administered was
consistently higher in the group fed the standard formula. Overall, subjects
randomized to the disease-specific formula experienced better numerical
biochemical control and better clinical outcomes when expressed on a numerical
and percentage basis. These included surrogate markers of diabetes control such
as serum glucose and glycohemoglobin, as well as clinical outcomes such as
incidence of infections and pressure ulcers. These findings confirm that the
disease-specific formula provides better glycemic control, poses no risk to
lipoprotein metabolism, and provides for better clinical outcomes.
PMID- 9646298
TI - Preparing dietetic professionals for practice in the 21st century: how can
educational programs respond to changes in health care?
PMID- 9646299
TI - Early enteral nutrition in surgical patients.
AB - There is increasing evidence that delivery of nutrients via the gastrointestinal
tract reduces the septic morbidity in severely injured patients. This article
reviews the most current data and also reviews the importance of the gut
associated lymphoid tissue as an important factor in maintaining the host
defenses.
PMID- 9646300
TI - Nutritional modulation of immunity and the inflammatory response.
AB - The metabolic derangements of the injured or stressed patient are governed by
multiple factors that partially include the severity of insult, preexisting
illnesses, available energy reserves, and appropriateness of intervention. The
normal response to injury is further characterized by the release of
proinflammatory and antiinflammatory mediators that exert potent effects on
cellular and organ function. Although brief periods of starvation and catabolism
are tolerable in otherwise healthy individuals, protracted nutritional
deprivation can manifest as immunocompromise, irreversible organ injury, and late
mortality. Moreover, patients with severe injuries or preexisting illnesses who
exhibit exaggerated inflammatory responses may be further predisposed to such
deleterious consequences following the insult. The optimal supply of appropriate
nutrients and substrates in such circumstances has often been championed as a
necessary means of restoring proper cellular metabolism, wound healing, immune
competence, and proper organ function. However, much debate surrounds the present
efficacy of nutritional therapy in modulating the immune response associated with
injury and stress. This article seeks to assess the merits of nutritional
therapeutics in the injured patient through available biological and clinical
evidence.
PMID- 9646301
TI - n-3 versus n-6 polyunsaturated fatty acids in critical illness.
AB - The effects of n-6 and n-3 polyunsaturated fatty acids (PUFA) on protein
metabolism, cell-mediated immunity, and production of cytokines and prostanoids
were studied in experimental animals and patients with esophageal cancer. In the
experimental study using a rat burn model, n-6 PUFA increased serum interleukin-6
(IL-6) and tumor necrosis factor (TNF), alpha (P < 0.05), and decreased nitrogen
balance (NB) (P < 0.05), when compared with a fat-free control. But addition of n
3 PUFA reduced TNF-alpha and IL-10 (P < 0.05) and improved NB (P < 0.05).
Suppressed delayed type hypersensitivity (DTH) induced by burn injury, which was
not influenced by n-6 PUFA, was significantly improved by the administration of n
3 PUFA. n-6 PUFA tended to increase, and n-3 PUFA significantly decreased the
endotoxin translocation. DTH, granulocyte-macrophage colony-stimulating factor,
and eicosapentaenoic acid (EPA) content increased proportionately with the
intravenous dose of fish oil emulsion. The effects of n-6 and n-3 PUFA were
studied in the patients who underwent surgery for esophageal cancer. In the group
of patients fed by total parenteral nutrition with soybean oil emulsion, the
serum IL-6 significantly increased at 2 and 6 h after operation (P < 0.05).
Oral/enteral supplementation of EPA ethyl ester (1.8 g/d) significantly reduced
the postoperative IL-6 production (P < 0.05 at 1, 2, and 6 h after operation),
and improved cell-mediated immune function 3 wk after operation (P = 0.05).
During the chemoradiation therapy, cell-mediated immune function was improved
significantly in the patients fed enterally with EPA ethyl ester (n = 5), when
compared with the patients without EPA (n = 14).
PMID- 9646302
TI - Anabolic agents in trauma and sepsis: repleting body mass and function.
AB - Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are potent
anabolic agents. Exogenous GH improves nitrogen metabolism in patients undergoing
surgery; however, the anabolic effects of GH in cases of multiple injury, burn,
and sepsis are equivocal. Moreover, few data are available concerning the effects
of GH in organ failures. Exogenous IGF-1 attenuates catabolism in animal trauma
models. A clinical trial, however, did not confirm the anabolic actions of IGF-1.
Further knowledge of the interaction between the GH/IGF-1 axis in critical
illness is essential for GH and IGF-1 therapy. Theoretically, the improved
nitrogen metabolism achieved with exogenous anabolic agents may provide
functional benefits. However, only a few studies have confirmed the beneficial
effects of GH on body function in trauma and sepsis. GH treatment decreases the
postoperative depression of hand grip strength. GH also stimulates wound healing.
Both GH and IGF-1 exert their effects on immune system, suggesting that these
anabolic agents are potentially beneficial for the prevention and treatment of
sepsis. On the contrary, inhibition of polymorphonuclear neutrophil apoptosis and
the potentiation of PMNs by GH may have harmful effects on the systemic
responses. Further studies are required to determine the safety and clinical
benefits of GH administration in critical illness.
PMID- 9646303
TI - Implications of critical illness, injury, and sepsis on lean body mass and
nutritional needs.
PMID- 9646304
TI - Interleukin 8 can affect inner ear function.
AB - The chemokine interleukin 8 (IL-8) was instilled into the round window niche of
rats through a small perforation in the tympanic membrane in order to study its
effect on inner ear function by electrophysiological and morphological
techniques. The frequency-specific auditory brainstem response (ABR) was recorded
at the frequencies 4, 8, 10, 12, 16 and 20 kHz just before and 1, 2, 5 and 14
days after instilling IL-8 to ascertain the hearing level during each interval.
Morphological examination by light microscopy was performed during the same
interval following the instillation of IL-8. On day 1, the rise in ABR threshold
was within 5 dB SPL (non-significant elevation). However, a significant threshold
elevation (above 5 dB SPL) occurred in high-frequency areas (16 and 20 kHz) on
day 2, and in middle frequency areas (10 and 12 kHz) on day 5 with sensorineural
hearing loss type intensity-latency curves. By day 14, the elevated thresholds
had returned to pre-instillation levels. In the lowest areas (4 and 8 kHz), no
significant threshold elevation was detected at any time during the observation
period. By light microscopy, on day 1, clusters of inflammatory cells
(predominantly neutrophils) were observed just outside the round window membrane
(RWM), while only a few neutrophils were detected in the cochlea. These cells
were still present outside the RWM on day 2. The neutrophils had disappeared by
day 5 and only macrophages were present on the middle ear side of the RWM.
However, throughout the observation period, the organ of Corti and stria
vascularis appeared to be intact. These results suggest that IL-8 in the middle
ear cavity is able to influence inner ear function.
PMID- 9646305
TI - Stereocilia-like structures in the endolymphatic sac in Meniere's disease and
acoustic neuroma.
AB - The vestibular aqueduct was surgically removed in 3 patients undergoing
labyrinthectomy due to severe Meniere's disease (MD). Stereocilia-like structures
were found in the luminal contents of the endolymphatic sac (ES) in all of these
patients. The ES from 18 patients with acoustic neuroma were used as controls. In
1 of these, numerous stereocilia-like structures were found in the ES and in 3
additional patients, a few isolated cilia-like structures were disclosed. The
findings may suggest an ongoing hair cell degeneration in the inner ear that is
more advanced in patients with MD. The data also suggest that the endolymphatic
duct is patent and that a longitudinal flow of endolymph also occurs in patients
with MD.
PMID- 9646306
TI - Long-term fate of Plastipore in the middle ear.
AB - Four Plastipore prostheses, removed at revision surgery 7-10 years after
implantation, have been examined. The gross appearance of the prostheses was
preserved. The prostheses were surrounded by a fibrous tissue capsule and showed
fibrous tissue ingrowth localized in peripheral zones. Foreign-body giant cells
and macrophages were detected in small numbers. Histologic evidence of breakdown
of the prostheses, in the form of microdisintegration of the walls of micropores,
was detected on a small scale. Compared to the massive foreign-body reactions
reported in short-term studies, the tissue reaction apparently subsides with time
and becomes insignificant. Strict criteria for insertion should be regarded.
PMID- 9646307
TI - Ciliary beat frequency, olfaction and endoscopic sinus surgery.
AB - We assessed prospectively changes in olfaction and ciliary beat frequency (CBF)
after functional endoscopic sinus surgery (FESS) in 70 patients with chronic
sinusitis. CBF was measured by the microscopic-photometry technique 2, 4 and 6
months after FESS. Olfaction was evaluated by the Erlangener Smell Identification
Test. Preoperative CBF was markedly reduced due to the infectious process. CBF
was significantly improved (p < 0.001), reaching normal values 6 months
postoperatively despite the endoscopic examination revealing normal nasal mucosa
at around 3 months. The pattern of improvement of CBF was linear being more rapid
between months 4 and 6. After operation olfactory-impaired patients were improved
subjectively and objectively (p < 0.001 and p = 0.003). We conclude that impaired
olfactory ability and CBF are significantly improved after FESS, and FESS demands
longer postoperative follow-up periods for at least 6 months even if the clinical
evaluations were normal.
PMID- 9646308
TI - Correlation between objective and subjective assessments of nasal patency.
AB - The correlation between the subjective sensation of nasal patency and nasal
resistance (NR) to airflow was examined in a large population. The subjective
estimation was assessed by a visual analogue scale and the NR by active anterior
rhinomanometry in 158 subjects. Evaluation and statistical analysis--including
correlation and regression analysis--were computerized. A statistically
significant correlation was found between the subjective and objective values (r
= -0.301, p < 0.001). There was no correlation between the parameters if the
groups with or without nasal obstruction were evaluated apart. In 84% of the
cases, the narrower side of the nose was identified with both the objective and
the subjective methods. Statistically significant correlations were exhibited
between the subjective and the objective measures if unilateral NR and the
ipsilateral subjective values were related to each other (n = 316, r = -0.476, p
< 0.001), in both cases, on the side of the higher and the lower NR. The best
correlation was found on the side of the higher NR, that is when nasal breathing
is more impeded. Subjective estimation seems to be sufficient only to indicate
the more obstructed side of the nose independently from the dimensions of the NR
values.
PMID- 9646309
TI - Results after resection of intraoral cancer and reconstruction with the free
radial forearm flap.
AB - Between 1989 and 1996, 47 patients with an intraoral squamous cell carcinoma
underwent tumor resection and reconstruction with a free volar forearm flap.
Tumor resection and neck dissection were performed by a head and neck surgeon and
the free tissue transfer by a plastic surgeon. Preoperative radiation therapy was
given to 44 of 47 patients and postoperative radiation therapy to 2. One other
patient was not irradiated. There were 15 females and 32 males, with a mean age
of 61 years. The primary site of the cancer was the tongue in 15 cases, the floor
of the mouth in 15, the tonsil in 10, the bucca in 3 and the retromolar trigone
in 4 cases. The flap was harvested from the left forearm in 34 and from the right
in 13 patients. The mean operation time was 10 h (range 6-20) and the mean
intraoperative bleeding was 486 ml (250-2,500). Forty-four of 46 flaps healed
completely. Twelve revisions on 9 free flaps were performed between 6 h and 6
days postoperatively. Overall revisional surgery was done in 9 of 47 cases (19%).
Two flaps could not be saved (4%). Infections/fistulas in the neck occurred in 11
of 46 cases (24%). Complete healing of the donor site occurred at a mean of 2.5
months (1-5). Nine patients developed complications at the donor site, 3
hematomas and 6 superficial infections (19%). Twenty-seven of 47 patients are
still alive (57%). The mean survival time was 49 months (16-71).
PMID- 9646310
TI - Platysma myocutaneous flap including the external jugular vein with special
reference to neck dissection.
AB - Although platysma myocutaneous flap (PTMCF) is suitable for a small intraoral
defect, combination with neck dissection (ND) decreases the viability. Therefore,
a version of PTMCF was devised to increase the viability. This version consists
of three points: preservation of the external jugular vein (EJV), preservation of
the facial artery after skeletonization from the submandibular gland, and a new
incision around the flap. This procedure was applied to 21 patients with
intraoral cancer. All 21 patients underwent some kind of ND. The average viable
area of transferred skin was 80%. This rate was significantly better than that
for 46 previous cases using Farr's modification with ND, in which the facial
artery was divided. Viability of the flaps was analyzed by the vessels preserved,
especially by EJV. ND is not a contraindication with this version.
PMID- 9646311
TI - Late-onset sensorineural hearing loss in Coffin-Lowry syndrome.
AB - The Coffin-Lowry syndrome (CLS) is a rare clinical entity where patients present
with a characteristic facies, mental retardation and bone abnormalities. So far
about 60 cases have been reported. Sensorineural hearing loss is not a
characteristic symptom and a late-onset hearing loss has not been reported so
far. We report on 4 brothers with CLS, aged 9-17 years, of whom 3 suffered from a
severe sensorineural hearing loss with an onset during late childhood and
adolescence after a normal hearing during early childhood. CT scans revealed no
cochlear abnormalities. The boys were successfully equipped with hearing aids. It
is suggested that in all CLS patients the hearing ability should be examined
during early infancy and retested regularly in cases with normal hearing as these
cases indicate that in CLS a late-onset hearing loss is possible during late
childhood and adolescence.
PMID- 9646312
TI - Bilateral facial nerve palsy: four case reports.
AB - Bilateral facial nerve palsy is relatively uncommon and may occur in association
with a variety of neurological, infectious, neoplastic or degenerative disorders.
Presentation is made of 4 cases of bilateral facial diplegia due to a refractory
anemia with excess of blasts, a Lyme disease and a tuberculoid leprosy. In one of
these patients the cause of bilateral seventh-nerve palsy was unknown (Bell's
palsy). Facial palsy returned to normal after treatment with steroids in 3
patients. The patient with myelodysplastic syndrome did not show any improvement
and died 6 months after diagnosis.
PMID- 9646313
TI - Management of chylous fistula using the fibrin adhesive set.
AB - Chylous fistula complicates 1.1% of all radical neck dissections, and 2.4% of
left-sided dissections. The standard treatment of established chylous leak in the
reported cases is a pressure dressing applied to the lower neck. Here we present
a case of chylous fistula, where conservative methods failed to cope with this
complication. The additional application of a fibrin adhesive set was a
successful modality of treatment.
PMID- 9646314
TI - Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia by
local irradiation.
AB - We report an 85-year-old man presenting with angioimmunoblastic lymphadenopathy
with dysproteinemia (AILD) of the palatine tonsil with cervical and axillary
lymph node enlargement, pleural effusion and hypergammaglobulinemia. The patient
was treated in Internal Medicine with combined chemotherapy with steroids which
resulted in a complete remission. However, he returned almost 1 year later with
an ulcerative lesion in the left palatine tonsil, with no lymph node involvement.
Considering that the patient was an elderly person, chemotherapy had been
administered during the initial admission, tumor cells appeared to originate from
T cells and relapse occurred only in the local lesion, the lesion was treated by
local irradiation using 60Co at a dose of 40 Gy, which produced a complete
resolution. Radiotherapy appeared to be effective for the treatment of localized
lesions of AILD.
PMID- 9646316
TI - [Bone metastases. 2].
PMID- 9646315
TI - Lupus pernio with involvement of nasal cavity and maxillary sinus.
AB - Histological demonstration of sarcoidosis affecting the paranasal sinus is rare
in the clinical practice. In this paper, we present a case with a diagnosis of
lupus pernio with extensive involvement of the nasal cavity and the right
maxillary sinus. Long before being diagnosed as having lupus pernio, the patient
had had a long history of nasal obstruction and had been treated surgically
without success on 3 occasions. The literature on the topic is reviewed.
PMID- 9646317
TI - [Interventional therapy of primary and secondary tumors of the spine].
AB - Therapeutic interventions in the skeletal system are an essential part of
interventional radiology. Although in terms of figures these procedures are
applied less frequently, they are very effective. Percutaneous transarterial
embolization of a spinal tumor is well-established interventional treatment. It
is primary treatment for preoperative devascularization, but also for palliation
of pain and for reduction of tumor volume. As an alternative access for
embolization, direct percutaneous puncture of a vertebra is used. A new and
promising technique is vertebroplasty, the percutaneous injection of acrylic
surgical cement in destroyed vertebrae. The present paper discusses indications,
technique, results and complications of these interventional therapeutic
modalities in the treatment of primary and secondary spinal tumors.
PMID- 9646318
TI - [Surgical management of skeletal metastases of the extremities].
AB - Operations on skeletal metastases of the extremities represent the most frequent
surgical treatment in orthopedic oncology. From 1970 to 1997, 340 patients were
operated on in 383 surgical procedures in the Orthopedic Department of the
University of Heidelberg. Carcinoma of the breast and renal cell carcinoma were
the most common primary tumors. Operations concerned mainly the femur with
acetabulum (55%) and the humerus with glenoid (25%). A pathologic fracture
occurred in 51%. While in these cases surgical treatment is absolutely necessary,
it is contraindicated in preterminal patients. In imminent fractures or
peripheral compression syndromes, the indication is relative and has to be
justified on a multidisciplinary basis. Marginal resection of the tumor is
allowed because of the limited life expectancy of most patients. Only in patients
with solitary metastases and a better prognosis the resection of metastasis
margin can be more extensive. Intensification of local therapy by adjuvant
irradiation is indicated in an R2 situation, depending on the patient's
prognosis. An analysis of our cases from 1994 to 1996 exemplifies the increasing
use of modular tumor endoprostheses (52%). In meta-diaphyseal and diaphyseal
cases, cement-augmented osteosynthesis is mainly used (34%). The application of
these established reconstruction techniques after metastasis resection in cases
with adjuvant radiotherapy assures a pain-free extremity capable of weight
bearing.
PMID- 9646319
TI - [Surgical therapy of spinal metastases].
AB - Bone metastases of the vertebral spine occur frequently after breast cancer,
hypernephroma or thyroid carcinoma. Located commonly in the lumbar and thoracic
spine, half of the lesions are found in the vertebral body, but in many cases
lamina and pedicles are also involved. Pain resistant to conservative treatment,
vertebral compression fracture and segmental instability, together with
progredient neurologic deficits and para- or tetraplegia, all make operative
intervention mandatory. In this article dorsal decompression and stabilization
are compared to ventral decompression and compound osteosynthesis. Segmental
stability and life-time prognosis of the patient are important factors to decide
on the best surgical procedure. Dorsal decompression without stabilization should
only be performed as a palliative procedure in patients with an inoperative
tumor, poor prognosis, or if the estimated postoperative segmental stability
seems to be sufficient. In cases of a solitary metastasis, after radical
resection of the primary tumor and when the prognosis is good total vertebrectomy
can be performed. In addition to surgical treatment, adjuvant chemotherapy and/or
radiation therapy should be performed in a multidisciplinary setting.
PMID- 9646320
TI - [Surgical management of pelvic metastases].
AB - Due to a rise in life expectancy as well as improved adjuvant and diagnostic
measures the incidence of clinically symptomatic metastases has significantly
increased. In terms of indication and operative technique in the treatment of
these lesions the biologic age, general condition, diagnosis, stage and activity
of the disease and the patient's prognosis are highly important. Different
techniques of joint replacement have been described to treat patients suffering
from metastatic disease of the periacetabular region, being resistant to any kind
of adjuvant therapy. From 1977-1996 21 patients with a periacetabular lesion
received a tumor prosthesis following internal hemipelvectomy (average age 60
years; average survival 23.1 months). Perioperative complication rate was 42%,
functional results were good (n =), fair (n = 9) and poor (n = 2). Mobilisation
and analgesia are the most important therapeutic goals. The quality of the
patient's life postop is the major point.
PMID- 9646321
TI - [Prognosis of skeletal metastases].
AB - Surgical resection of osseous metastases is becoming more and more important in
obtaining longer overall survival in carcinoma patients. In 228 cases surgically
treated at our institution between 1980 and 1993, the survival was 49% after 1
year, 32% after 2 years, 22% after 3 years and, finally, 11% after 5 years.
Retrospectively evaluated, breast and thyroid carcinoma proved to be of positive
prognostic influence and lung cancer of negative significance. As a main
significant parameter, further extraosseous metastases were evaluated. The
prognostic influence of the number of osseous lesions could only be demonstrated
in breast and renal cell carcinoma without involvement of further organs. Age and
location of the skeletal lesions proved to be of no prognostic influence. Based
on these prognostic parameters, three subgroups of patients with worse, median
and good long-term survival could be defined. In conclusion, the indication and
amount of surgery can be based on these prognostic factors, leading to a decrease
in morbidity and hospitalization time in patients with limited survival.
PMID- 9646322
TI - [Biometric planning of clinical-orthopedic studies. The optimal test].
AB - A determinant for the evidence of a clinical trial is the magnitude of the sample
size. The proper sample size can be easily computed with the knowledge of alpha,
power and effect size. Standard values for alpha and power in clinical trials are
5% and 90%, respectively. As a consequence, effect size is crucial for the sample
size. The effect size has to be determined by the clinician according to medical
considerations. Possible consequences of sample sizes that are either too small
or too large are discussed with regard to the meaning of alpha, Power and effect
size. Trials with improper small sample sizes have a high risk of false negative
results, and may subsequently prevent the application of a possibly effective
therapy. Trials with improper large sample sizes may result in statistically
significant differences without any clinical relevance.
PMID- 9646323
TI - [Remembering Prof. M. H. Retting].
PMID- 9646324
TI - [Cartilage regeneration and substitution].
PMID- 9646325
TI - Developmental expression of cytochrome P450 enzymes in human liver.
AB - Drug-metabolizing cytochrome P450 enzymes, the major phase I enzymes, are active
in human liver already at very early stages of intrauterine development, although
presumably at fairly low concentrations and in low numbers. During maturation,
these enzymes go through various developmental programmes towards adulthood. The
major increase both in abundance as well as in number of different enzymes takes
place after birth, probably during the first year of life. Detailed information
concerning these developmental changes is still limited. The major drug
metabolizing P450 enzymes appear to be primarily members of the CYP3A subfamily
in all stages of development. The balance between different members of this
subfamily, however, undergoes significant switches from the foetal predominant
CYP3A7 to the major adult form CYP3A4. The ontogeny of the other cytochrome P450
enzymes is less well characterized, but the major switch-on appears to occur
mainly after birth. Developmental expression of P450 enzymes is one of the key
factors determining the pharmacokinetic status of developing individuals both pre
and postnatally.
PMID- 9646326
TI - Effect of chronic administration of magnesium sulfate on 1-methyl-4-phenyl
1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice.
AB - This investigation was aimed to study the effect of magnesium on 1-methyl-4
phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Four
groups of mice were given magnesium sulfate (MgSO4.7H2O) in drinking water at
four different concentrations of 0.0 g/l (control), 2.5 g/l (low), 5.0 g/l
(medium) and 10.0 g/l (high) respectively for a period of 16 weeks; these animals
also received MPTP (30 mg/kg, intraperitoneally daily) during the last five days
of Mg treatment. Other four groups of mice were given similar dose regimen of
MgSO4 but received injections of saline instead of MPTP. Seventy-two hr after the
last dose of MPTP, neurobehavioural studies including locomotor activity, pole
climbing test and heart nociception test were performed and striata were
collected for the analysis of dopamine. The results of this study show that
treatment of mice with MgSO4 or MPTP individually has no effect on their
behaviour. Concomitant administration of low dose of MgSO4 (2.5 g/l) along with
MPTP produced increase in motor activity and latency to heat stimuli; whereas
medium and high doses of MgSO4 in combination with MPTP produced opposite (as
compared to low dose) effects resulting in a decrease in motor activity and
latency to heat stimuli and increase in pole climbing time. However, MgSO4 dose
dependently exacerbated MPTP-induced depletion of striatal dopamine. The
mortality was drastically increased (30-55%) in the animals receiving combined
treatments of MPTP and MgSO4 as compared to the mice treated with MPTP alone
(12%). This study clearly points towards the ability of MgSO4 to modify MPTP
induced neurotoxicity.
PMID- 9646327
TI - Effect of stem cell factor, interleukin-6, nitric oxide and transforming growth
factor-beta on the osteoclast differentiation induced by 1 alpha,25-(OH)2D3 in
primary murine bone marrow cultures.
AB - Osteotropic hormones and cytokines are involved in the differentiation of
osteoclast progenitors from haematopoietic stem cells to multinucleated
osteoclasts which mediate bone resorption. Stem cell factor, interleukin-6,
nitric oxide, and transforming growth factor-beta are implicated in the
regulation of bone resorption by osteoclast. We test whether stem cell factor,
interleukin-6, nitric oxide, and transforming growth factor-beta affect the
generation of osteoclast-like multi-nucleated cells induced by 1 alpha,25
(OH)2D3. 1 alpha,25-(OH)2D3 increase the generation of osteoclast-like cells
retaining osteoclast characteristics including multinuclearity and positive
staining for tartrate-resistant acid phosphatase. Combined treatment of stem cell
factor with interleukin-6 synergistically potentiates the ability of 1 alpha,25
(OH)2D3 to generate tartrate-resistant acid phosphatase-positive multinucleated
cells. However, either stem cell factor or interleukin-6 alone does not induce
the generation of tartrate-resistant acid phosphatase-positive multinucleated
cells. Transforming growth factor-beta produces a biphasic effect on osteoclast
generation induced by 1 alpha,25-(OH)2D3. Transforming growth factor-beta
stimulates osteoclast generation at low concentration (0.1 ng/ml) whereas it
suppresses the formation of osteoclast-like cell at higher concentration (1
ng/ml). Sodium nitroprusside, a donor of nitric oxide, almost completely inhibits
the generation of 1 alpha,25-(OH)2D3-induced osteoclast at high concentration
(100 microM), but it significantly enhances the osteoclast generation at low
concentrations (3 microM). These results suggest that stem cell factor,
interleukin-6, transforming growth factor-beta, and nitric oxide interact with 1
alpha,25-(OH)2D3 to modulate the differentiation of hematopoietic precursors
toward committed osteoclast precursors.
PMID- 9646328
TI - Cadmium uptake from apical membrane of LLC-PK1 cells via inorganic anion
exchanger.
AB - Effects of Na+, Cl-, OH- and HCO3-, and an inorganic anion exchange inhibitor
(HCO3-/Cl-), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, on Cd uptake from
the apical membrane of LLC-PK1 cells were investigated to elucidate the mechanism
of Cd uptake by these cells. Furthermore, the initial uptake of Cd incubated at
different temperatures was analyzed by using the Arrhenius plot to test if Cd is
taken up by the cells via the carrier-mediated process. The cells were incubated
with 1 microM CdCl2 for 30 min. at 37 degrees in phosphate buffer containing NaCl
at pH 5.5 or 7.4. Cd accumulation by the cells at pH 7.4 was about 5 times higher
than at pH 5.5. Replacement of NaCl in the phosphate buffer with KCl or mannitol
decreased the Cd accumulation at pH 7.4 about 80%, but had no effect at pH 5.5.
The addition of 2 mM NaHCO3 to the pH 7.4 buffer containing NaCl significantly
increased the Cd accumulation, and pretreatment of the cells with the inorganic
anion exchange inhibitor abolished this effect of NaHCO3 on Cd accumulation. The
cells were incubated for 10 min. at different temperatures with 1 microM CdCl2 in
the phosphate buffer containing NaCl at pH 7.4 in the presence or absence of 2 mM
NaHCO3 or at pH 5.5 in the absence of NaHCO3. In all cases, the Arrhenius plots
of Cd accumulation were nonlinear. The breakpoint was observed at about 30
degrees in the Cd accumulation at pH 7.4 in the presence of NaHCO3, suggesting
the involvement of a carrier-mediated process. This breakpoint was not as clear
in the Cd accumulation at pH 7.4 in the absence of NaHCO3 and not observed at all
at pH 5.5. These findings suggested that Cd is partially taken up from the apical
membrane of LLC-PK1 cells via the inorganic anion exchanger and the uptake of Cd
is more efficient at alkaline pH and in the presence of Na+, Cl- and HCO3-.
PMID- 9646329
TI - Effect of t-butylhydroperoxide on chloride secretion in rat tracheal epithelia.
AB - Oxidative stress has been known to play important roles in various inflammatory
diseases of lung such as allergic bronchitis, dust particle-induced inflammatory
diseases, or chronic bronchitis. However, the effects of oxidants on Cl-
secretion in tracheal epithelia have not been determined. To examine the effects
of oxidants on Cl- secretion of the airway epithelia rat tracheal epithelial
cells were cultured on porous filters and short circuit current (Isc) was
measured in an Ussing chamber system. t-Butylhydroperoxide, which was widely used
as a model substance to study the mechanism of cell injury resulted from
oxidative stress, induced a transient increase in Isc by dose-dependent manner.
The response was not observed in Cl(-)-free medium, and inhibited by 100 microM
bumetanide. N(-Diphenyl-1,4-phenylene-diamine (DPPD, 5 microM), an inhibitor of
lipid peroxidation, blocked the t-butylhydroperoxide response. When t
butylhydroperoxide was added after the administration of forskolin or H-89, a
protein kinase A inhibitor, the t-butylhydroperoxide-induce Isc increase was
abolished. Pretreatment of indomethacin (10 microM) completely inhibited the t
butylhydroperoxide response, but pretreatment of thapsigargin (1 microM) did not,
t-Butylhydroperoxide induced gradual increases in cytosolic Ca2+ level, and
increased [3H]arachidonic acid release in the presence of thapsigargin. These
results indicate that t-butylhydroperoxide stimulates Cl-secretion via activation
of phospholipase A2 and subsequent production of cyclooxygenase metabolities by
Ca(2+)-dependent and -independent mechanisms.
PMID- 9646330
TI - Short-term effects of nicotine on bone and calciotropic hormones in adult female
rats.
AB - This study assessed the effects of two months nicotine treatment on bone
formation and resorption end-points in adult, female rats. In addition, the
concentrations of calciotropic hormones which included parathyroid hormone,
calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in rats (7 months
old) were determined. All animals received either saline (n = 7/group), nicotine
(3.0 mg/kg/day) (n = 7/group) or nicotine (4.5 mg/kg/day) (n = 7/group) via
subcutaneous implantation of osmotic minipumps containing either saline or
nicotine for a period of two months. Serum, right tibia, left femur and lumbar
vertebra (3-5) were collected for determination of hormonal concentrations as
well as various parameters, including histomorphometry, bone mineral density,
bone mineral content and vertebral strength. Although nicotine-treated rats
showed a lower level of 25-hydroxyvitamin D [54.4 +/- 3.1 ng/ml for the 3.0
mg/kg/day and 55.8 +/- 2.8 for the 4.5 mg/kg/day group] (mean +/- S.E.M.) as
compared to controls (74.8 +/- 2.8 ng/ml) (P < 0.01, Newman-Keuls test), no
significant difference could be detected for the levels of the remaining
hormones. Similarly, no statistical differences were detected on
histomorphometric end-points, bone mineral density, bone mineral content and
vertebral strength of rats. We conclude that, in spite of lowering serum 25
hydroxyvitamin D by about 30%, nicotine administration of two months duration
does not alter bone mass, strength or formation and resorption end-points.
PMID- 9646331
TI - Amlodipine dynamic effects and myocardial pharmacokinetics in the isolated and
perfused guinea-pig heart.
AB - Myocardial dynamic effects and pharmacokinetics of amlodipine were studied in the
isolated retrogradely perfused and spontaneously beating guinea-pig heart.
Pharmacokinetic analysis of drug accumulation showed one-compartment
characteristics with an half-life of 76 min. Whereas disposition exhibited two
compartment characteristics with phasic half-lives of 25 and 174 min.,
respectively. Myocardial drug accumulation was increased by 600 times at steady
state compared to the perfusion liquid. Dynamic effect parameters were studied
during increasing amlodipine concentrations from 0.16 to 220 nM. Dynamic steady
states developed within 20 min. Coronary flow-rate increased with an Emax of 119%
and an EC50 of 1.2 x 10(-8) M. Amlodipine produced inhibitory effects on
contraction amplitude and velocities of contraction and relaxation. Observed Emax
values and curve-fitted EC50-values were: 97, 97 and 94% and 1.10(-8), 7.7 x 10(
9) and 2.1 x 10(-8) M, respectively. Heart frequency was not changed. Oxygen
consumption increased markedly to a maximum of 44% at 3 x 10(-8) M amlodipine and
then decreased to nearly initial values. The frequency-corrected QT-interval
decreased to a maximal extent of 20% at the three highest concentrations.
Myocardial efficiency expressed as the ratio of contraction velocity times
frequency to oxygen consumption exhibited a progressive decline to about 2% of
initial values. The PQ-interval was not changed and the QRS-interval showed only
a small but significant decrease at the highest amlodipine concentration. No
arrythmogenic effects were observed. The study demonstrated a very slow
accumulation and disposition of amlodipine in the guinea-pig heart with a steady
state myocardial drug concentrating accumulation of 600 times. Marked increase in
coronary flow-rate and oxygen consumption accompanied by a progressive negative
inotropic effect were observed.
PMID- 9646332
TI - The influence of selected herd factors and a badger-intervention tuberculosis
control programme on the risk of a herd-level trade restriction to a bovine
population in Ireland.
AB - The risk of a trade restriction to cattle herds between 1990-1994, as a result of
failing the tuberculin skin test or disclosure of visible lesions in the
abattoir, was compared in two areas in East Offaly, Ireland. Cattle herds from
the Project area where badgers were systematically removed over a 7-year period
(1989-1995) were compared to herds from a Control area where no wildlife
intervention programme had taken place. A Cox proportional hazard model
indicated, for example, that the risk of a herd-level trade restriction to herds
with 30 animals in the Control area was 1.4 times the risk to similar-sized herds
in the Project area. The study provides evidence that a badger-control programme
is effective in reducing the risk of a trade restriction to cattle herds as the
badger represents an important reservoir of Mycobacterium bovis infection for
cattle.
PMID- 9646333
TI - Evaluation of an enrofloxacin-treatment program against Mycoplasma gallisepticum
infection in broilers.
AB - Three chicken broiler breeder flocks, 7 months of age, were confirmed to have
Mycoplasma gallisepticum (MG) infection, based on culture of tracheal swabs. A
total of fifty-five 7-day-old embryos from the three MG-positive flocks had an
average 27.4% prevalence of MG-infection in their vitelline membrane. Sixty
randomly selected MG isolates (30 from individual tracheas of breeders and
another 30 from individual vitelline membrane of embryos) were highly sensitive
in vitro to enrofloxacin (100%). Three broiler flocks (averaging 15,000 birds per
flock) from the same three MG-infected chicken boiler breeders were divided into
halves. The first halves were subjected to an enrofloxacin-treatment program and
the other halves were controls. Sera collected at different ages of the broiler
flocks were tested by the enzyme-linked immunosorbent assay for antibodies to MG.
The absence of MG titers at 45 days of age in birds subjected to the enrofloxacin
preventive program was compared to an average prevalence of 15.9% in the controls
(p < 0.05). The lack of MG titers in 45-day-old birds subjected to the
enrofloxacin-treatment program was associated with lower better feed-conversion
ratios (p < 0.05).
PMID- 9646334
TI - Effect of different East Coast fever control strategies on disease incidence in
traditionally managed Sanga cattle in Central Province of Zambia.
AB - A clinical trial, including five East Coast fever (ECF) control strategies
(involving tick control and/or immunisation by infection-and-treatment) in five
different groups of traditionally managed Sanga cattle, was conducted in Central
Province of Zambia over 2.5 years between 1992 and 1995. Two groups were kept
under intensive tick control by weekly acaricide treatment by hand spray; (one
immunised and one non-immunised), two groups were under no tick control (one
immunised and one non-immunised), and a fifth, immunised group was maintained
under strategic tick control (18 sprays yr-1). ECF-specific mortality was highest
in the non-immunised and non-treated group, while no difference in ECF-specific
mortality could be observed between animals treated for ECF by immunisation or by
tick control. Acaricide treatment and/or immunisation reduced the risk of
clinical ECF by 92%. The results of an artificial challenge experiment at the end
of the field trial indicated that about 60% of the animals in the control group
had become infected with Theileria parva without showing clinical signs. ECF
incidence in non-vaccinated cattle markedly declined six months after
immunisation--suggesting that the carrier state induced by immunisation did not
lead to a persistent high incidence, and might accelerate the progress to
endemicity.
PMID- 9646335
TI - A case-control study of acute ibuprofen toxicity in dogs.
AB - A case-control study used data in the National Animal Poison Control Center
database to characterize risk factors for gastrointestinal ulceration and acute
renal failure subsequent to the acute ingestion of ibuprofen in the dog. For
gastrointestinal ulceration (GIU) subsequent to ibuprofen ingestion, four factors
differentiated the 116 cases from the 93 controls. Risk of GIU was lower for dogs
where the time from ingestion to intervention was known as opposed to missing
(adjusted odds ratio (aOR) = 0.12, p = 0.0001). Risk of GIU was also lower for
the Labrador breed (aOR = 0.22, p = 0.004). Risk of GIU was higher for each unit
of the logarithm of time to intervention (aOR = 2.63, p = 0.0002) and for the
German Shepherd breed (aOR = 5.67, p = 0.14). For acute renal failure (ARF)
subsequent to ibuprofen ingestion, two factors differentiated the 80 cases from
the 64 controls. Risk of ARF was lower for dogs where the time from ingestion to
intervention was known as opposed to missing (aOR = 0.15, p = 0.0001). Risk of
ARF was higher for each unit of the logarithm of time to intervention (aOR =
2.16, p = 0.01). Although this study failed to describe a dose-response
relationship, it appears that there are significant breed differences in
susceptibility to GIU subsequent to ibuprofen exposure. Time to intervention was
critical for both GIU and ARF outcomes. Dogs, particularly German Shepherds,
ingesting even small amounts of ibuprofen, may need to be managed aggressively.
PMID- 9646336
TI - Observations on ethnoveterinary medicines in Trinidad and Tobago.
AB - In 1995 research was conducted in Trinidad and Tobago with the aim of collecting
knowledge on ethnoveterinary medicines in order to lay a foundation for further
scientific study and validation. This paper describes only the ethnoveterinary
practices used in the poultry sub-sector. A four stage process was used to
conduct the research and document these ethnoveterinary practices. 28
ethnoveterinary respondents were identified using a modified Rapid Rural
Appraisal (RRA) technique, the student essay method. Semi-structured interviews
were conducted with these respondents as well as with 30 veterinarians, 27
extension officers and 19 animal health assistants/agricultural officers, and the
7 key respondents that they identified. 5 participatory workshops were then held
with 55 of the respondents interviewed to discuss the data generated from the
interviews and to determine dosages for some of the plants mentioned. 12 plant
species were used to treat 4 categories of health problems common to poultry
production. Aloe vera, Bryophyllum pinnatum, Citrus sp. and Momordica charantia
were the main medicinal plants being used.
PMID- 9646337
TI - An outbreak of East Coast fever in a herd of Sanga cattle in Lutale, Central
Province of Zambia.
AB - An outbreak of East Coast fever (ECF) occurred in an experimental herd of Sanga
cattle maintained under a traditional rangeland grazing system at Lutale, Central
Province of Zambia. Two groups of cattle had been kept under different tick
control regimens for several years prior to the introduction of the disease and
epidemiological information on the outbreak were recorded. Weekly tick control
was no sufficient to achieve full protection against Theileria parva infection.
Systematic body temperature monitoring seems to be a good method for early
detection of infection resulting in an important reduction of the case fatality
rate after treatment with anti-theilerial drugs.
PMID- 9646338
TI - [Graduate and Continuing Education Committee of the German Society of Radiology].
PMID- 9646339
TI - [Evaluating tumor vascularization with Doppler ultrasound].
AB - Tumor vessels are structurally and functionally abnormal. The degree of
vascularity determines a tumor's aggressiveness, as well as its radiosensitivity
and chemosensitivity. Assessing tumor vascularity may help in differential
diagnosis and assist therapy monitoring. Together with other imaging methods,
Doppler sonography has been evaluated for the assessment of tumor vascularity but
has proven to be difficult to evaluate. Using quantitative analysis methods,
Doppler sonography was shown to carry differential diagnostic and prognostic
information as well as to reflect vascular changes during radiotherapy. Its
clinical role, however, remains to be determined. With current technology neither
blood volume flow nor microvessel density can be reliably assessed in a tumor
using Doppler sonography, because it is insensitive to capillary blood flow.
Upcoming developments such as harmonic imaging and contrast media that generate
stimulated acoustic emissions are expected to significantly improve sensitivity.
PMID- 9646340
TI - [B-mode ultrasound and modern Doppler ultrasound methods in diseases of the
thyroid gland and parathyroid glands].
AB - Color-coded duplex sonography is the main innovation in diagnostic ultrasound in
recent years. It allows quantification of tissue vascularity and appreciation of
vascular morphology. Due to the unique thyroid hypervascularity in Graves'
disease this diagnosis can be made with color Doppler sonography alone. The
decrease of vascularity during the course of disease is a relevant parameter
throughout the follow-up. Hypervascularity is also observed within areas of
inflammatory infiltration in thyroiditis, but the level is lower than in Graves'
disease. Sonographic differentiation of benign from malignant thyroid nodules is
not possible yet. Color-coded duplex sonography is not useful in the initial
detection of parathyroid masses, but may be helpful in distinguishing parathyroid
lesions from other cervical masses.
PMID- 9646341
TI - [A multicenter study of diagnostic criteria in ultrasound mammography.
Statistical pitfalls and ways out of the data jungle].
AB - This paper demonstrates the statistical processing of data from a multicentric
study. Seventy-seven patients with a suspicious, solid breast mass were included
in a two-center study, using clinical breast examination, mammography, and
ultrasound. The assessment was formalized using a uniform evaluation sheet. The
prospective results of the examinations were compared with the histologic report.
The degree of interdependence between an examiner's diagnosis and diagnostic
criteria used was assessed using the kappa statistics. We found that despite
standardized assessment, the criteria used for differential diagnosis were at
least partially different. The criteria valid for diagnosis at both centers were
whether a mass fitted well into the surrounding tissue or led to destruction or
architectural distortion, whether it was fixed to the surrounding tissues, as
assessed by sonopalpation maneuvers, and whether it borders were sharp or
unsharp.
PMID- 9646342
TI - [Diagnosis of pulmonary diseases with transthoracic ultrasound].
AB - The indications or ultrasound in the evaluation of pulmonary disorders are
described. Clinical applications are several lung diseases in adults and
especially in children. In specific, well-defined applications, the feasibilities
of ultrasound are promising. Sonography provides important additional information
to chest X-ray and is even superior to CT under special circumstances. Pulmonary
sonography is a useful link between conventional X-ray and more expensive cross
sectional imaging. In the evaluation of pulmonary diseases at present the
potential of ultrasound is not optimally used.
PMID- 9646343
TI - [After-care of TIPSS patients. Comparison between color Doppler ultrasound and
portography].
AB - PURPOSE: Comparison of color Doppler sonography and venous portography in
patients with a transjugular intrahepatic portosystemic stent shunt (TIPSS).
MATERIALS AND METHODS: In a prospective study 40 consecutive patients with TIPSS
underwent venous portography and color Doppler sonography on the same day as
follow-up. Shunt velocities were recorded within the TIPSS at the proximal
(hepatic vein segment) and distal part (portal vein segment). RESULTS: In 28
patients with functioning TIPSS the mean shunt velocity ranged between 30 and 120
cm/s (median 60 cm/s) at the portal vein segment and between 60 and 155 cm/s
(median 82 cm/s) at the hepatic vein segment. There was a significant increase of
the mean shunt velocity in the hepatic vein segment (P < 0.001). In 12 patients
with compromised TIPSS the mean shunt velocity was reduced to 26 +/- 7 cm/s at
the portal venous end (P < 0.0001). CONCLUSION: Because of an accelerated shunt
velocity in the hepatic vein segment a site-specific evaluation of both TIPSS
endings is necessary with color Doppler sonography. In compromised TIPSS the
shunt velocity is reduced at the portal venous end. Color Doppler sonography is a
valid non-invasive means for follow-up of patients with TIPSS.
PMID- 9646344
TI - [Ultrasound anatomy and pathology of the elbow joint in the child and in the
adult].
AB - The aim of this study was to evaluate the sonographic anatomy of the elbow joint
in children and adults and to point out the indications for an ultrasound
examination after elbow joint trauma. The study was carried out using isolated
joint specimens, muscle specimens and cadaver limbs. Additionally, a clinical
trial was performed using high-resolution ultrasound probes (7.5-12 MHz). When
assessing standard sections, one has to consider both the position of the elbow
joint in the frontal plane and the position of the forearm during pro- and
supination. The outstanding advantage of this method, especially in children, is
the possibility of a dynamic examination with evaluation of the articular
cartilage and with a comparison to the healthy contralateral elbow joint.
PMID- 9646345
TI - [Dynamic assessment of contrast medium enhancement in Doppler ultrasound imaging.
Current status].
AB - Findings in previous investigations have indicated that contrast-enhanced colour
Doppler can be used to improve the demonstration of characteristic features of
neovascularization in malignancies. However, the quantification of the increase
in colour Doppler signals after Levovist in the cited study relied only on
descriptive criteria defined by the investigator, resulting in a subjective
scoring system. A computer-assisted method for quantitative analysis of colour
pixel density is a novel approach for objective assessment of colour Doppler
signal after contrast media administration. After microbubble contrast medium
injection in 47 patients, carcinomas and benign lesions behaved differently
regarding degree, onset and duration of Doppler enhancement. However, the high
interindividual variability and the temporal variations of the Doppler signal
still limit the value of these criteria for prospective diagnosis. Rapid image
acquisition techniques are needed in order to apply the necessary mathematical
processing before the contrast kinetics can be used for diagnostic purposes.
PMID- 9646346
TI - [3-dimensional echo-enhanced transcranial Doppler ultrasound diagnosis].
AB - Echo-enhancing agents improve the signal intensity of transcranial Doppler
signals, enabling a novel approach of three-dimensional transcranial vascular
imaging by Doppler ultrasound. The basic principle, system requirements and early
clinical results with a custom built system are described. Transcranial color
Doppler imaging was performed through the temporal bone acoustic window. During
i.v. administration of the transpulmonary stable, galactose-based echo-enhancer
Levovist (Schering) the video output of the ultrasound scanner was digitized and
the spatial position of the recorded frames was simultaneously registered using a
mechanical position sensor. After automatic segmentation of the color
information, the 3D datasets were reconstructed offline using a Unix-based
workstation (Silicon Graphics). Visualization was achieved by maximum intensity
projection or surface visualization techniques. Administration of Levovist
resulted in good enhancement of the vascular Doppler signal intensity, enabling
acquisition of a 3D dataset of the complete circle of Willis with an imaging
window of approximately 3-5 min for one i.v. injection. The vascularity of tumors
could be recorded as a 3D dataset and further analyzed. The power Doppler
technique with echoenhancement proved a valuable tool for 3D dataset recording.
3D datasets clearly facilitated the diagnosis of the vascular anatomy and lesion
vascularity and provided additional information on localization of feeders,
vascular displacement and extent of tumor vascularity.
PMID- 9646347
TI - [Use of the ultrasound contrast medium levovist in after-care of liver transplant
patients. Improved vascular imaging in color Doppler ultrasound].
AB - INTRODUCTION: A study was carried out to determine whether an improvement in the
detection of vascular signals in patients after orthotopic liver transplantation
can be achieved by the use of ultrasound contrast medium in colour Doppler
sonography. MATERIAL AND METHODS: In the early postoperative follow-up of liver
transplant recipients, 31 colour Doppler sonograms were obtained in 21 patients
before and after intravenous injection of the ultrasound contrast agent Levovist
(Schering, Berlin). A grading score with four categories was used to evaluate the
sonograms with special regard to the visibility of colour and flow signals in the
hepatic artery and also in the portal vein and the hepatic veins. The arterial
and portal venous signals were evaluated in the hepatic portal and in the left
and right lobe. RESULTS: With contrast enhancement significantly better arterial
signals were seen in 20 of 31 sonograms for the hepatic portal, in 22 for the
right lobe and in 26 for the left lobe. Better portal vein signals were obtained
in 17 of 31 examinations for the right lobe and in 16 for the left lobe; only
little improvement was obtained for the main stem of the portal vein. For the
hepatic veins there was no significant improvement. CONCLUSIONS: Early vascular
complications after liver transplantation usually occur in the hepatic arteries.
With the use of contrast-enhanced colour Doppler sonography, better detection of
arterial and peripheral portal signals can be achieved; peripheral portal vein
branches can be helpful in finding small arteries.
PMID- 9646348
TI - [Diagnosis of vesicoureteral reflux with echo-enhanced micturition
urosonography].
AB - AIM: To ascertain the diagnostic efficacy of reflux sonography with the
application of the echo-enhancing agent Levovist in comparison with X-ray voiding
cystourethrography (VCUG). PATIENTS AND METHODS: Echo-enhanced voiding
urosonography (VUS) and VCUG were performed successively in one examination
session in 114 children referred for the investigation of possible vesicoureteral
reflux (VUR). After sonography of the urinary tract the bladder was filled with
normal saline and Levovist was administered. Reflux was diagnosed when
hyperechogenic, floating microbubbles appeared in the ureters or renal pelvises.
RESULTS: A total of 226 kidney-ureter units were available for analysis. Reflux
was diagnosed in 80 units. All grades of reflux were represented. In 15 kidney
ureter units VUR was diagnosed with echo-enhanced VUS but was not seen at VCUG.
The contrary was true in 3 units. High sensitivity and specificity in comparison
to the VCUG could be attributed to the echo-enhanced VUS. The long imaging window
attainable with Levovist makes the documentation of convincing images possible,
contributing to the high diagnostic efficacy. CONCLUSION: Echo-enhanced VUS is
comparable to VCUG in the diagnosis of reflux.
PMID- 9646349
TI - [SieScape panorama imaging in radiologic diagnosis].
AB - Through high-performance computer processing it has become possible to realize a
new ultrasound imaging process: SieScape imaging. This method provides extended
field of view images in real time using successive ultrasound images obtained
when a standard transducer is scanned over a distance of up to 60 cm without any
position sensor. SieScape offers new possibilities to view topographical anatomy.
It is especially advantageous for scanning extended and tubular structures as
well as large and enlarged organs and big pathologic volumes. Parallel scanning
sequences allow documentation comparable to that of computed tomography. In
addition, just as in magnetic resonance, variable imaging planes can be realized.
The following describes the results obtained with SieScape in a multitude of
clinical applications, especially in examinations of throat, thoracic and
abdominal walls, breast, and intraabdominal organs as well as the soft tissues
and small vessels of the extremities. The experience gathered with SieScape
imaging--its advantages as well as its potential limitations, such as the
formation of artefacts--is described.
PMID- 9646350
TI - [SieScape--a new dimension of ultrasound imaging in pediatric radiology].
AB - The extended field of view imaging procedure named "SieScape" provides, for the
first time, a mode of establishing in real time a sonographic picture up to 60 cm
in length. This allows the display of large organs or tumors as well as large
areas of the body in a single view, without having to assemble several pictures.
Furthermore, pathological findings can be shown in full size in their
surroundings. This method makes it considerably easier to convey sonographic
results to the therapist who is not present at the investigation and to control a
finding, for instance a tumor, during therapy.
PMID- 9646351
TI - [Native tissue harmonic imaging].
AB - Native Tissue Harmonic Imaging is a new way of ultrasound image processing that
addresses the difficult-to-image patient. By using a Gaussian shaped transmit
pulse it is possible to separate from the returning echo the harmonic component
without overlapping with fundamental reflections. The improved image quality
leads to higher diagnostic confidence so that the use of further imaging
modalitites is unnecessary.
PMID- 9646352
TI - [Equipment-independent ultrasound tissue characterization of testis and
prostate].
AB - The result of a B-scan ultrasound examination is strongly dependent on the type
of the used B-system, the chosen system parameters and the experience and
critical analysis of the clinical investigator. The estimation of quantitative
acoustic parameters, independent of the type of the used B-system, is one way to
overcome the subjective nature and the problems of the interpretation of B-scan
images. A procedure was developed to determine acoustical tissue specific
parameters (ultrasound attenuation, relative backscatter coefficient) in terms of
the ultrasound spectroscopy and to correct the system effects. A requirement for
the calculation of acoustical parameters is the availability of primary rf echo
signals without any preprocessing. Up to now measurements of phantom materials
and in-vivo investigations on human testis and prostate have been carried out.
The effects of pathological changes in the tissue state on the acoustical
parameters are demonstrated in some examples.
PMID- 9646353
TI - [Dissection of the inferior vena cava by Fogarty balloon maneuver. A rare
complication in venous surgery].
AB - Laceration of the inferior vena cava is an uncommon complication of vascular
surgery. This report describes the radiologic features (CT and venography) of a
patient with iatrogenic dissection and perforation of the vessel as a sequel of a
Fogarty balloon procedure for deep venous thrombosis.
PMID- 9646354
TI - [Dose distribution in conventional CT and spiral CT and on the topic of dose
reduction with spiral CT].
AB - OBJECTIVE: To compare spiral CT with conventional CT with regard to the dose
distribution in the irradiated body and to examine when an increase in the table
feed in spiral CT leads to a dose reduction compared with conventional CT.
METHODS: In order to show the dose distribution, films were exposed in an acrylic
phantom. The nominal slice thickness was 5 mm; the slice distance in conventional
CT was 5 and 10 mm; the table feed in spiral CT was 5 and 10 mm per rotation
(pitch 1 and 2). The integral doses delivered in spiral CT and conventional CT
were related to the table feed per rotation or slice distance, respectively, and
were compared arithmetically with each other. RESULTS: Spiral CT showed reduced
dose fluctuations in axial direction compared with conventional CT. Only in
conventional CT with a slice distance of 5 mm did the axial dose distribution
show relative dose peaks near the rotation axis. The longer the body region to be
examined is, the less table feed is necessary in spiral CT for a dose reduction.
From a length of 15 times the slice thickness, a pitch of > 1.1 leads to a
reduction of the integral dose compared with conventional CT. CONCLUSIONS: The
continuous table feed in spiral CT results in evenly distributed axial dose
distributions compared with the discontinuous scanning in conventional CT. The
spiral technique can give an important contribution to dose reduction in CT.
PMID- 9646355
TI - [Comment on the contribution by J. Zaers et al. Quality assurance in roentgen
mammography].
PMID- 9646356
TI - [Comment on the contributions regarding quality assurance in mammography].
PMID- 9646357
TI - [Sclerosing lesion of the sphenoid bone. Fibrous dysplasia of the sphenoid bone
of the sclerosing type].
PMID- 9646358
TI - [With 2001: no more free physician position. Needs prognosis of the Central
Institute].
PMID- 9646359
TI - [Radiology scenario 2000. Need-dependent physician supply, economic aspects and
graduate education in diagnostic radiology: the quadrature of the circle? 2].
PMID- 9646360
TI - Gentacoll hampers epithelialisation and neovascularisation in excisional wounds
in hairless mice.
AB - Our aim was to analyse the effect of Gentacoll on the rate of epithelialisation
and neovascularisation in wound healing. Standardised circular full thickness
dermal wounds 2.25 mm in diameter were created on the dorsum of each ear on 24
hairless homozygous mice (n = 48). The cartilaginous layer was left intact. The
wounds were treated in a randomised blinded fashion with bovine collagen implants
with gentamicin (Gentacoll) (n = 17); bovine collagen implants without gentamicin
(n = 15); and Silicone film (n = 16). Epithelialisation and neovascularisation
were measured directly by intravital video-microscopy and computerised planimetry
immediately after the wounds had been made and every third day until the wounds
closed. Only five of the wounds treated with Gentacoll (n = 17) epithelialised
completely; and their mean (SEM) epithelialisation time was 22.8 (1.6) days,
significantly longer than controls without gentamicin (n = 15) for which the
corresponding figures were 14.5 (0.6) days. In nine wounds treated with Gentacoll
the ear cartilage in the wound bed perforated and two wounds developed severe
inflammation, which was followed by self-mutilation. Neovascularisation was
incomplete in all of the wounds in the Gentacoll group, whereas it was completed
by 25.3 (0.7) days in the control group treated with implants without gentamicin.
In the silicone treated group (n = 16), epithelialisation was completed by 12.7
(0.7) days and neovascularisation by 25.1 (0.5) days. None of wounds treated with
collagen or silicone alone showed reactions similar to the Gentacoll-treated
ears. Gentacoll hampers epithelialisation and neovascularisation, and might
damage exposed cartilage.
PMID- 9646361
TI - The effect of Gingko biloba extract (Egb 761) as a free radical scavenger on the
survival of skin flaps in rats. A comparative study.
AB - Free radicals may have a role in pedicle flap necrosis. We undertook this study
to compare the effect of various antioxidants and scavengers of free radicals
such as vitamin E, vitamin C, deferoxamine, and Gingko biloba extract (Egb 761)
on McFarlane caudal-based dorsal rat flaps. Fifty rats were divided into five
groups of 10 animals each. One group served as a control (saline) group. The
remaining four groups were given vitamin C 340 mg/kg, deferoxamine 150 mg/kg, Egb
761 100 mg/kg, and vitamin E 20 mg/kg. The necrosed area of flap was
significantly reduced in the deferoxamine (p < 0.001), Egb 761 (p < 0.001), and
vitamin C (p < 0.05) groups compared with the control group. Vitamin E had no
effect on distal flap necrosis (p = 0.20).
PMID- 9646362
TI - Inhibition of plasma extravasation after burns by D-myo-inositol-1,2,6
trisphosphate using digital image colour analysis.
AB - D-myo-inositol-1,2,6-triphosphate (1,2,6-IP3) has beneficial effects in
experimental, progressive burn-induced ischaemia and oedema. A 1 cm2 full
thickness burn was made in the skin of 20 rats with a hot aluminium rod followed
by infusion of 1,2,6-IP3 (60 mg.kg.-1 h-1) or isotonic saline (n = 10 in each
group). One hour later Evans blue was injected intravenously. Colour photographs
of the area of the burn were taken in a standard manner before the burn and at
intervals for three hours afterwards. The photographs were analysed by digital
image colour analysis using normalised red-green-blue values. The increase in
normalised blue values between 60 and 180 minutes after the burn was
significantly reduced in animals treated with 1,2,6-IP3 compared with control
animals (p < 0.001). Spectrophotometric analysis of extravasated Evans blue in
the skin 180 minutes after the burn showed that it had been significantly
inhibited by treatment with 1,2,6-IP3 (p < 0.001). In conclusion, digital image
analysis allowed repeated evaluation over time and confirmed previous data about
the ability of 1,2,6-IP3 to inhibit extravasation of plasma after burns.
PMID- 9646363
TI - Contraction and myofibroblasts in restored skin.
AB - Myofibroblasts and the contraction of split skin-graft donor sites were studied
in 18 patients. For each patient five samples were studied, taken on days 0, 14,
21, 28, and 35. On each occasion the extensions and densities of myofibroblasts
were calculated. After the initial measurement, the subsequent extensions were
expressed in percentages of the first, resulting in mean measurements of 100, 95,
97, 99, and 99%, respectively. The myofibroblasts in 10 dermic fields were
counted under light microscopy at a magnification of 1000 marked with anti-alpha
smooth muscle actin antibodies using immunoperoxidase, resulting in the means of
0.2, 3.8, 1.3, 1.3, and 0.4, respectively. The contraction and the increase in
density of myofibroblasts were transitory and significant in the samples measured
on day 14, but in sample 35 neither of the variables was significantly different
from the initial sample. These variables evolved concurrently, corroborating the
hypothesis that myofibroblasts are responsible for the contraction.
PMID- 9646364
TI - Reinnervation of split skin grafts in humans: comparison of two different methods
of operation.
AB - Studies on the reinnervation of split skin grafts have produced contradictory
results. As the difference in sensitivity may be caused by the method of
grafting, sensory reinnervation was studied in split skin grafted by two
different methods. Thirty-nine patients given split skin grafts after the
excision of malignant melanoma took part in the study. In 17 patients, split skin
was grafted on to the intact muscle fascia. In another 22 patients the skin was
grafted directly on to the muscle after the fascia had been removed. In all
patients, sensitivity (to touch, heat/cold, and pain) was tested on the grafts
and the skin from the opposite side. Sensory functions on grafted skin were
generally reduced. Patients with split skin grafted on to the intact muscle
fascia had better reinnervation than the ones in whom the fascia had been
removed. However, individual patients from both groups showed surprisingly good
reinnervation of transplanted skin. The reasons for this finding are not clear,
but it is quite possible that the characteristics of the grafted skin have some
influence on the reinnervation.
PMID- 9646365
TI - Closure of large pharyngo-oesophageal fistulas with free flap transfer after
resections for cancer.
AB - Postoperative salivary fistulas still remain a serious and potentially lethal
problem in head and neck reconstruction particularly if the fistula is large and
involving one half or more of the circumference of the pharyngo-oesophagus.
Pedicled flaps have traditionally been the flaps of choice for closure of these
fistulas, but the results are often disappointing. During the period 1982 to
1995, we have used either a radial forearm free flap or a jejunal free flap to
close large and complex pharyngo-oesophageal fistulas after resection for cancer
in 15 patients. Although two patients developed major fistulas that required
additional operations for closure, successful closure was achieved in all but one
case: the success rate was therefore 14/15 (93%). We consider that jejunal flaps
are suitable for circumferential pharyngo-oesophageal reconstruction and forearm
flaps for non-circumferential defects.
PMID- 9646366
TI - Free flap transfers for the treatment of osteomyelitis of the lower leg.
AB - Since 1974, 31 cases of soft tissue defects associated with osteomyelitis of the
lower leg have been treated by free flap transfer and followed up for more than
three years. Four patients developed recurrences. Two of them were reoperated on
and healed well. One patient was reoperated on three times, but remained
infected. One patient developed a fever, but improved after intravenous infusion
of antibiotics. Of the eight patients who underwent vascularised muscle transfer
to the dead space created by saucerisation of the osteomyelitis, none developed
signs of recurrence. By contrast, the four patients who developed recurrences
were those in whom the dead space could not be completely filled with the free
flap. It therefore seems important that after saucerisation, well-vascularised
soft tissue should be used to pack the dead space completely to prevent
recurrence of the osteomyelitis.
PMID- 9646367
TI - Use of intraperitoneal vessels in reconstructive microsurgery: an account of 117
cases.
AB - The purpose of this study was to evaluate our experience of microvascular
anastomosis of intraperitoneal vessels. Between 1985 and 1994, 117 microsurgical
reconstructions were done using intraperitoneal vessels. These included
oesophageal reconstruction (n = 106), reconstruction of the hepatic arterial,
superior mesenteric arterial, or portal venous system (n = 8), and reconstruction
of the chest or abdominal wall (n = 3). We used 129 intraperitoneal arteries and
117 intraperitoneal veins. Of a total of 246 intraperitoneal vessels, five
hepatic arteries, seven splenic, 14 gastroepiploic, six superior mesenteric, 178
jejunal, 30 ileocolic, four middle colic arteries or veins, and two portal veins
were used for microvascular anastomosis. The overall successful rate for these
reconstructive cases was 97% (114/117). Microsurgical use of intraperitoneal
vessels is a safe and developing procedure in plastic and reconstructive surgery.
PMID- 9646368
TI - Classification, recording, and cleft palate surgery at the Uppsala Cleft Palate
Centre.
AB - This paper describes the classification system, method of recording, and surgical
techniques used in Uppsala for children with isolated cleft palate. The
classification is based on the system described by Kernahan and Stark and the
more detailed system described by the American Cleft Palate Association.
Separation of the hard palate into thirds, and into right and left sides, assures
a detailed description of the cleft, and separates small morphological
differences. The longitudinal registration system was introduced into the Uppsala
Cleft Palate Centre in 1967. After the initial recording at the time of primary
surgery, it is repeated at 5, 8, 11, 14, 17, and 20 years. By emphasising the
therapeutic aspects of various stages of growth, it has been possible to limit
the recording to once every third year. This has resulted in an important
reduction in the dose of radiation without compromising the reliability of the
results. Children born before 1975 had clefts of both the soft and hard palate
closed at 18-24 months in a one-stage procedure. For children born in 1975 and
later a two stage technique has been used, while clefts limited to the soft
palate only have been closed entirely in the first operation. At first, the soft
palate cleft was closed at 18 months of age and the hard palate at 4 to 5 years.
The timing was changed in several steps to the present soft palate closure at 6
months and hard palate closure at 2 years of age.
PMID- 9646369
TI - Morphology of isolated cleft palate in children, including Robin sequence,
treated with one or two-stage operations.
AB - A classification developed at the Uppsala Cleft Palate Centre was used to
describe isolated cleft palate in children with and without Robin sequence. The
study included 109 patients born between 1968 and 1983 with isolated cleft
palate. In 46 patients the cleft was closed in a single operation and 63 were
treated by a two-stage procedure. Of the 109 patients 70 (64%) were girls. In 19
patients (17%), the cleft was limited to the soft palate. Ninety of the patients
had clefts of the hard palate and in 39 (43%) of these patients the clefts
involved less than a third of the hard palate. Only four children (4%) had total
clefts of both the hard and soft palate. The Robin sequence was diagnosed in 14
children (13%), and it was more common in boys with isolated cleft palate (7/39;
18%) than in girls (7/70; 10%). In those with Robin sequence the cleft was U
shaped anteriorly in nine (64%), with great variations in width. Generally,
however, the clefts were wider than other clefts involving the hard palate. In
all cases, closure of the soft palate was followed by a spontaneous reduction in
the width of the remaining cleft in the hard palate. The greatest improvement was
noted in subjects with the U-shaped clefts, in whom the position of the tongue
probably had the greatest influence on the development of wide primary clefts. In
10 subjects with clefts of the soft palate only and 12 patients in whom the cleft
included part of the hard palate (35%), only the first operation of the two-stage
procedure was done because there was no residual cleft. In these subjects the
original cleft had involved less than a third of the length of the hard palate.
PMID- 9646370
TI - Dental abnormalities and ectopic eruption in patients with isolated cleft palate.
AB - The aim of this study was to evaluate the influence of cleft size and surgical
treatment on the development of permanent teeth in patients with isolated cleft
palate. The series comprised 109 children with isolated cleft palate, 70 girls
and 39 boys, including 14 patients with Robin sequence. The patients were grouped
according to the sagittal extent of the palatal cleft, measured on dental casts
obtained before the primary palate surgery. Forty-six children were treated by
one-stage palatoplasty, and 63 in two stages. The dentition was studied on
orthopantomograms taken at 5, 8, 11, and 14 years of age. Congenitally missing
permanent teeth (third molars excluded) were found in 33 subjects (30%). Children
with large clefts had significantly more missing teeth than children with small
clefts. The tooth most usually missing was the mandibular second premolar,
followed by the maxillary lateral incisor, and the upper second premolar. The
incidence of dental malformation was 23%, mostly mild forms. Ectopic eruption of
the upper first permanent molars was seen in 23 (45%) of the subjects with large
clefts, and in 18 (31%) of those with small clefts. The surgical method did not
significantly affect the direction of the eruption. There is a correlation
between cleft size and hypodontia, dental deformity, and ectopic eruption.
Children with Robin sequence had almost the same incidence of hypodontia,
malformed teeth, and ectopic eruption as children with large clefts. There was no
correlation between surgical method and ectopic eruption of the maxillary first
permanent molars.
PMID- 9646371
TI - Use of titanium dental implants as an integrated part of a CLP protocol.
AB - The problem of edentulousness in the cleft area of patients with cleft lip and
palate was formerly resolved with a conventional fixed bridge construction, but
this approach did not always prove optimal. Nowadays, in these patients the
bridge can be substituted by a crown on an osseointegrated titanium implant
fixture. The concept of dental rehabilitation using titanium implants has
gradually merged into our routine treatment for patients with cleft lip and
palate. In this report we describe our surgical technique using osseointegrated
titanium implants and evaluate our result in patients with cleft lip and palate.
Sixteen patients with cleft lip and palate, 11 men and five women, were divided
into two groups: group 1 consisted of six patients who did not need bone grafting
prior to the fixture installation, and group 2 comprised 10 patients who had
additional bone grafting three months before the fixture installation. Abutments
were applied six months after fixture installation. Dental crowns and fixed
bridges were then constructed. All patients were seen on regular follow-up
visits. Routine roentgenograms were obtained preoperatively and when the
abutments were applied. Photographs were taken at these occasions and also after
the prosthodontic work was completed. Of a total of 31 fixtures, all except two
were osseointegrated at the time of the abutment connection, and the remaining 29
have all been functional during the observation period, giving a success rate of
93%. In group 1 all fixtures (100%) were osseointegrated. The non-integrated
fixtures were found in group 2 giving a success rate of 91% in this group. The
mean follow-up time after fixture installation was six years and three months,
and the mean observation time with loaded fixtures was five years and six months.
PMID- 9646372
TI - Perforating branches: important contribution to the formation of the dorsal
metacarpal arteries.
AB - The perforating branches that originate from the deep palmar arch of the hand
have been studied to provide a complete anatomical description of these vessels
and assess their importance in the blood collateral pathway of the hand. We
injected latex into the arteries of 50 cadaveric hands of 25 adults, of both
sexes, all of Brazilian origin. These were dissected under a stereoscopic
microscope. The perforating branch of the second interosseous space originated
from the deep palmar arch in 80% of the cases, and it corresponded to the radial
artery passing through the second space in 16%; the one of the third interosseous
space originated from the deep palmar arch in 76% of the cases and from the
palmar metacarpal artery of the third interosseous space in 16%; the one of the
fourth interosseous space originated from the deep palmar arch in half the cases,
from the deep palmar branch of the ulnar artery in 14%, and from the palmar
metacarpal artery of this space in 18%. The perforating branch of the second
space anastomosed with the second dorsal metacarpal artery (DMA) in 60% of the
cases and formed it in 10%; the one of the third space anastomosed with the third
DMA in 20% and formed it in 64%; the one of the fourth space anastomosed with the
fourth DMA in 8% and formed it in 78%. These vessels are an important anastomotic
pathway between the dorsal carpal network and the deep arteries of the hand and
are important in the supply to the dorsum.
PMID- 9646373
TI - Tissue expansion of a tube flap during the last transferring stage in
reconstructions of the face and neck.
AB - The tube flap technique is an old and safe distant flap for soft tissue
reconstruction, and tissue expansion is a well known way of repairing adjacent
soft tissue defects. We have experience of expanding a tube flap during the last
transferring stage for reconstruction of the face and neck after a burn. The tube
flap from the right acromiopectoral region, of which the two pedicled stumps had
been transferred to the face and neck separately, was successfully extended to
double its length in 17 days without changing the diameter of the flap by placing
a tissue expander under the tube flap. The tube flap tolerates tissue expansion
well, even after the pedicles of the flap have been transplanted to new
positions. In this way, a tube flap can be enlarged by tissue expansion when it
is used in certain cases of reconstruction.
PMID- 9646374
TI - Mycotic aneurysm in a free flap.
AB - A 41-year-old man developed a 3 x 4 cm wound after corrective osteotomies of his
distal tibia and fibula. The wound was debrided and covered with a free gracilis
muscle flap. Seven days after flap transfer, the arterial pedicle ruptured
adjacent to the anastomosis. Attempted repair of the aneurysm failed and the
graft was subsequently debrided. Intraoperative wound cultures grew Pseudomonas
and Enterobacter cloacae, which were attributed to formation of the aneurysm.
PMID- 9646376
TI - Establishing a polysomnography laboratory in India: problems and pitfalls.
PMID- 9646375
TI - Lipofibromatous hamartoma (neural fibrolipoma) of a flexor nerve of the index
finger.
AB - A 24 year old woman presented with a painless fusiform mass in her right index
finger. Exploration showed an enlargement of the nerve by fibrofatty tissue and
microsurgical intraneural dissection was done. Histological examination
identified the lesion as a lipofibromatous hamartoma of the nerve, which is both
rare and benign. There are different options for treatment of this lesion.
PMID- 9646377
TI - Sleep position and sleep stages: evidence of their independence.
AB - Recently we conducted a first ontogenetic study of sleep positions in the human,
which involved five groups of 10 subjects (5 males, 5 females) from each of the
following age categories: 3-5 years, 8-12 years, 18-24 years, 35-45 years, 65-80
years. They slept for 4 consecutive nights in the laboratory. Sleep positions
were recorded during 2 nights with super-8 time-lapse photography. In a first
report we presented results showing developmental trends in sleep position
shifts, position durations and in the use of prone, supine and side positions. In
the current report we present results showing that there was no significant
relationship between sleep stages and sleep positions in any group. Furthermore,
time-series analyses revealed no consistent pattern of position sequences in any
of the age groups. It is concluded that, while there are ontogenetic trends in
sleep position preferences, sleep positions are independent of sleep stages and
do not show consistent rhythmicity.
PMID- 9646378
TI - Effects of sleeping position and time after feeding on the organization of
sleep/wake states in prematurely born infants.
AB - Epidemiologic studies provide strong evidence for the conclusion that sleeping in
the prone position places infants at greater risk for sudden infant death
syndrome (SIDS). Prior studies in newborn infants found that in the prone
sleeping position there is less time awake and more quiet sleep, but little
change in the amount of active sleep. To determine whether the effects of
sleeping position on state distribution vary with time after feeding, we studied
prematurely born infants in both the prone and supine sleeping positions. Sleep
states were recorded each minute during interfeed intervals. Results demonstrate
expected effects of sleep position on state distribution: prone sleeping is
associated with a 79% increase in quiet sleep and a 71% decrease in time awake.
While the decreases in time awake are seen throughout the interfeed interval,
increases in quiet sleep in the prone position are found only within the first
hour and again near the end of the interfeed interval. These results are
consistent with the hypothesis that prone sleeping could increase risk for SIDS
by altering the organization of sleep, and that time after feeding may play an
important role in the expression of these effects.
PMID- 9646379
TI - Effect of age on EEG arousals in normal sleep.
AB - EEG arousals were quantified in 40 nocturnal polysomnographic recordings
belonging to four age groups (teenagers: 10 to 19 years; young adults: 20 to 39
years; middle-aged: 40 to 59 years; elderly: > or = 60 years). Ten subjects (five
males and five females) participated in each group. The subjects were healthy and
sound sleepers. All sleep recordings were preceded by an adaptation night which
aimed at excluding the presence of sleep-related disorders. The recordings were
carried out in a partially soundproof recording chamber and in a standard
laboratory setting. Arousal indices (AI), defined as the number of arousals per
hour of sleep, were calculated for total sleep time (AI/TST) and for all the
sleep stages. AI/TST increased linearly with age (r = 0.852; p < 0.00001):
teenagers (13.8), young adults (14.7), middle-aged (17.8), elderly (27.1). An age
related positive linear correlation was found also for the arousal indices
referred to NREM sleep (r = 0.811; p < 0.00001) and to stages 1 and 2 (r = 0.712;
p < 0.00001), while in stages 3 and 4 and in REM sleep, arousal indices showed
stable values across the ages. Overall, arousals lasted 14.9 +/- 2.3 seconds,
with arousal duration stable across the ages (range of means: 13.3-16.6 seconds)
and no relevant differences between NREM sleep (14.6 +/- 2.5 seconds) and REM
sleep (16.2 +/- 5 seconds). The paper discusses the impact of age on arousals,
the similarities between arousals and the phases d'activation transitoire, and
the consideration that arousals are physiological components of sleep.
PMID- 9646380
TI - The consequences of a week of insomnia. II: Patients with insomnia.
AB - Insomnia patients present with a consistent set of complaints that they generally
report as secondary to their poor sleep, including increased tension/confusion,
decreased vigor, personality disturbance, subjective overestimation of poor
sleep, increased body temperature, increased 24-hour whole-body metabolic rate,
and longer MSLT latencies. If there is a relationship between the poor sleep and
the secondary symptoms, then particularly poor sleep should exacerbate those
symptoms. Ten patients with insomnia were identified on the basis of a 2-night
screening protocol, then slept in the laboratory for 10 additional nights. On 7
of the nights, the insomnia patients had their wake-after-sleep-onset increased
so that their total sleep time was 80% of that on their second screening night,
resulting in an average of 254 minutes (of 480 minutes in bed) of sleep. The
spectrum of changes seen in these patients with insomnia who had very poor sleep
for a week was characteristic of mild partial sleep deprivation, and not
consistent with exacerbation of symptoms found in patients with primary insomnia.
Specifically, (1) these patients had a reduction as opposed to an increase in the
MSLT values, but the MSLT values at the end of the week remained within normal
limits; (2) these patients had decreased (as opposed to increased) whole
metabolic rate following nights of particularly poor sleep; (3) these patients
tended to underestimate (rather than overestimate) their subjective sleep latency
while being given particularly poor sleep; and (4) these patients displayed no
significant change in body temperature, subjective anxiety, or MMPI scores
following particularly poor sleep. It was concluded that the secondary symptoms
reported by patients with primary insomnia are probably not related to their poor
sleep per se. Data from previous studies that varied physiological arousal were
used to support the contention that the secondary symptoms of patients with
insomnia, and perhaps the poor sleep itself, occur secondary to central nervous
system hyperarousal.
PMID- 9646381
TI - Iron and the restless legs syndrome.
AB - STUDY OBJECTIVES: Using blinded procedures, determine the relation between serum
ferritin levels and severity of subjective and objective symptoms of the restless
legs syndrome (RLS) for a representative patient sample covering the entire adult
age range. DESIGN: All patient records from the past 4 years were retrospectively
reviewed to obtain data from all cases with RLS. All patients were included who
had ferritin levels obtained at about the same time as a polysomnogram (PSG), met
diagnostic criteria for RLS, and were not on iron or medications that would
reduce the RLS symptoms at the time of the PSG. SETTING: Sleep Disorders Center.
PATIENTS: 27 (18 females, 9 males), aged 29-81 years. INTERVENTIONS: None.
MEASUREMENTS AND RESULTS: Measurements included clinical ratings of RLS severity
and PSG measures of sleep efficiency and periodic limb movements (PLMS) in sleep
with and without arousal. Lower ferritin correlated significantly to greater RLS
severity and decreased sleep efficiency. All but one patient with severe RLS had
ferritin levels < or = 50 mcg/l. Patients with lower ferritin (< or = 50 mcg/l)
also showed significantly more PLMS with arousal than did those with higher
ferritin, but the PLMS/hour was not significantly related to ferritin. This last
finding may be due to inclusion of two 'outliers' or because of severely
disturbed sleep of the more severe RLS patients. CONCLUSIONS: These data are
consistent with those from a prior unblinded study and suggest that RLS patients
will have fewer symptoms if they have ferritin levels greater than 50 mcg/l.
PMID- 9646382
TI - Sleep and pulmonary function in children with well-controlled, stable asthma.
AB - The aim of this study was to assess sleep and pulmonary function in asthmatic and
control children. Forty children with well-controlled, stable asthma, and 34
controls (age range: 8.2 to 15.4 years) were monitored with wrist actigraphs and
peak-flow meters for 3 consecutive days. In addition, asthma severity was
assessed by subjective parental and self-rating scale and symptom checklist.
Asthmatic children had poorer sleep quality in comparison to their controls, as
manifested in lower percentages of quiet sleep (p < .05) and increased activity
level during sleep (p < .05). As expected, asthmatic children had reduced morning
peak expiratory flow measures (p < .01) and a higher evening-to-morning drop in
peak expiratory flow (p < .005). Peak-flow measures were significantly correlated
with subjective and objective sleep measures. In the asthmatic group, sleep
measures were also correlated with subjective asthma severity indices and symptom
checklists. We conclude that poorer sleep is associated with reduced pulmonary
function. The reduced sleep quality, coupled with subjective reports of increased
fatigue and reduced alertness found in asthmatic children, suggest that these
children are at risk for developing neurobehavioral deficits associated with
chronic sleep loss.
PMID- 9646383
TI - Importance of the pulse oximeter averaging time when measuring oxygen
desaturation in sleep apnea.
AB - The accuracy of pulse oximeters in measuring transient changes in oxygen
saturation (SaO2) may be affected by the oximeter time response. The aim of this
study was to assess the effect of modifying the pulse oximeter averaging time (T)
on the measurement of SaO2 in patients with the sleep apnea-hypopnea syndrome
(SAHS). Twelve patients with severe SAHS were studied during a nap with
conventional oximeters: Ohmeda 3740 and Criticare 501. We compared the readings
of each patient's oxygen desaturation measured simultaneously with two identical
pulse oximeters. One oximeter was the control (T = 3 seconds), and in the other T
was set from 3 seconds to 21 seconds. No significant differences in SaO2 were
found when both oximeters were set to the same T (3 seconds). In contrast,
increasing T to 12 seconds and 21 seconds in one of the oximeters resulted in
considerable and significant differences in the measured SaO2: oxygen
desaturation was underestimated by up to 60% when compared with the control. The
misestimation of SaO2 induced by settings of T which are within the range
selectable in conventional oximeters may be of epidemiological significance when
pulse oximetry is used as a complementary diagnostic tool to classify sleep
events in SAHS.
PMID- 9646385
TI - New rationales and methods for quantitative dream research outside the
laboratory.
AB - Laboratory studies of dreams are now at a low ebb, but past laboratory studies
provide a basis for the belief that some kinds of non laboratory studies, those
that focus strictly on dream content, may be useful for scientific purposes.
Further, the collection of Most Recent Dreams from individuals in specific types
of groups, along with the use of dream journals from individuals, can supply the
necessary sample sizes needed for reliable findings (100-125 for groups, 75-100
for individuals). An Excel 5 spreadsheet has improved the accuracy and speed of
data analysis with the well established and widely used Hall/Van de Castle coding
system and is available on the World Wide Web. A bar graph called the h-profile,
based on percentage deviations from norms and generated automatically by the
Excel 5 spreadsheet, makes it much easier to grasp comparisons of different
groups or individuals on many content indicators. Findings with the Hall/Van de
Castle system showing age, gender, individual, and cross-cultural similarities
and differences suggest that these new methods of data collection and analysis
provide a valid and low-budget way to further the understanding of dream content.
PMID- 9646384
TI - Cognitive executive dysfunction in patients with obstructive sleep apnea syndrome
(OSAS) after CPAP treatment.
AB - We have previously described impairments of cognitive executive functions in 17
patients with OSAS in comparison with 17 normal controls, as assessed by various
frontal-lobe-related tests. In the present study, 10 of these OSAS patients
treated with continuous positive airway pressure (CPAP) were reevaluated after 4
6 months of treatment. Neuropsychological tasks explored attention, short-term
memory span, learning abilities, planning capacities, categorizing activities,
and verbal fluency. Patients were found to have normalized most of their
cognitive executive and learning disabilities, but all the short-term memory
tests remained unchanged. These findings are discussed in light of the
contribution of the frontal-lobe-related systems to short-term memory functions,
and the eventual pathogenic role played by sleep fragmentation and nocturnal
hypoxemia, which are related to the occurrence of apneic and hypopneic events. In
conclusion, short-term memory impairment was persistent in OSAS patients despite
CPAP treatment for 4-6 months.
PMID- 9646386
TI - Presentation and reading level of sleep brochures: are they appropriate for sleep
disorders patients?
AB - OBJECTIVE: Sleep-disorders patients must be given information and health
education they understand. The purpose of this study was twofold: (1) to assess
suitability of American Sleep Disorders Association and National Sleep Foundation
patient education brochures; and (2) to assess one widely used brochure, using
patient input and patient literacy level, as a model for development of future
materials. DESIGN: Twelve American Sleep Disorders Association and National Sleep
Foundation brochures were assessed for reading level using Grammatik, and for
design, presentation, and motivating qualities using the Suitability Assessment
of Materials (SAM). Patient literacy level was assessed using the Rapid Estimate
Of Adult Literacy in Medicine (REALM). SETTING: The Louisiana State University
Medical Center sleep clinic, faculty private sleep clinic, and in the sleep
center laboratory. PATIENTS OR PARTICIPANTS: During the months of February-May
1997, 170 sleep disorders patients, 39% African American, 59% white participated
in the study. Participants ranged in age from 18-73 years, with a mean age of 46.
MEASUREMENTS AND RESULTS: Suitability scores for the 12 brochures indicate that
none scored in the superior range, 83% scored adequate, and 17% scored not
suitable. Ninety-four percent of the brochures were written on a 12th grade level
or higher, yet 37% of the sleep patients tested were reading at less than a 9th
grade level. Low-level readers were significantly more likely than their higher
reading-level counterparts to report that a brochure was too long (22% vs 12%; p
< .05), and that they would need help reading it (44% vs 3%; p < .001).
CONCLUSIONS: Patients need sleep information given to them on a level they
understand. When developing and selecting appropriate materials, reading level,
length, and suitability of written material should be considered.
PMID- 9646387
TI - Tunnel restorations in permanent teeth. A 7 year follow up study.
AB - The aim of the study was to perform a long-time evaluation of tunnel restorations
made in a general dental practice concerning survival time and type of failures.
267 Class I (87%) and II (13%) tunnel restorations in permanent teeth on 193
patients--mostly teenagers and young adults--were evaluated at annual recalls.
The observation time-span was 1-7 years. The restoration material was a
conventional glass ionomer cement in Class I tunnels and a silver cermet glass
ionomer cement in Class II tunnels. The yearly failure rate was 7% and the 50%
survival time was 6 years. The reasons for replacement were: marginal ridge
fracture (41%), recurrent caries (40%) and cavitation in approximal enamel (19%).
No differences in failure rate between Class I and II tunnels could be seen, but
recurrent caries was more frequent in Class I tunnels. Restorations made during
the second year of the study were more successful, indicating a learning effect.
Class I tunnel restorations in general practice can be an alternative to
conventional Class II restorations with narrow indications, i.e. patients with
relatively low caries activity, small approximal lesions in combination with
small demineralization zones in the enamel wall.
PMID- 9646389
TI - An experimental rabbit model for studying the healing of onlay bone grafts.
AB - An experimental rabbit model for studying the incorporation of onlay bone grafts
is described. Bone grafts from radius served as the graft and were positioned
beneath the mandibular basis. Six rabbits were used in the study and healing
periods of 6 weeks and 6 months were used. Each animal was operated twice and in
this way the grafts could be followed for six weeks on one side and for 6 months
on the contralateral side of the mandible. Healing of the bone graft with bony
union to the mandibular base with cortical bone in contact with cortical bone was
encouraging. Remodelling of the graft was observed after 6 weeks but was even
more pronounced after 6 months. After 6 weeks osteoclastic/osteoblastic activity
was primarily observed in the graft-recipient contact area and in the
intracortical compartment of the grafted bone. The resorption was most pronounced
in the borderlines of the graft. It is concluded that the described experimental
model can serve as a useful method for the study of onlay bone graft healing and
interaction between implants and bone transplants.
PMID- 9646388
TI - Risk factors for dental caries in 2-year-old children.
AB - This paper describes risk factors for dental caries identified among 491 2-year
olds in the city of Umea, Sweden. The study was performed as a risk screening for
dental caries according to a method developed for use by dental assistants. The
sugar consumption was high, 80% of the 2-year-olds had sweets once a week or more
and 25% had sweet beverages once a day or more frequently. In addition, 14% of
the children had a meal at night and most common were formula, bovine milk or
breastmilk. The majority of the parents brushed the child's teeth at least daily
using fluoride toothpaste. Among the children 6% had a chronic somatic disorder
and 6% had an intolerance towards specific foods, milk being the most common. The
high level of sugar consumption indicates that improved dental health education
focusing on the importance of limiting sugar consumption is needed among parents
with young children.
PMID- 9646390
TI - Hand dermatitis and symptoms from the fingers among Swedish dental personnel.
AB - Hand dermatitis among dental personnel has been an issue in recent years. Dental
personnel manually handle polymer materials which are known to irritate skin, and
also cause allergy. In addition, dental personnel wash their hands frequently,
and use latex gloves, and are therefore at risk to develop hand dermatitis. To
survey the occurrence of hand dermatitis among dental personnel, questionnaires
were sent to all dental teams (dentist + chair assistant) working in the two
northern Swedish counties. Referents were; researchers, teachers, and secretaries
from a university and high schools, from the same geographical area. The response
rate was 76% for dental teams, and 66% for referents. The results show that male
dentists reported a significantly higher prevalence of hand dermatitis than male
reference. In contrast to chair assistants and referents, dentists (both male and
female) reported a higher extent of hand dermatitis on the left than on the right
hand. There was an association between hand dermatitis among dental personnel
and; age, eczema in childhood, and hay fever but, not with; sex, asthma, frequent
washing of the hands, and glove use. Whitening of the fingers increased with
increasing age among dental personnel. Pricking was also associated with frequent
glove use. Pricking of the fingers was associated with sex, and 3.5 times more
common among female dental personnel than male dentists. Numbness of the fingers,
and finger pain was reported by more dentists than chair assistants and
referents.
PMID- 9646391
TI - Adverse health reactions in skin, eyes, and respiratory tract among dental
personnel in Sweden.
AB - Dental personnel manually handle products that contain monomers. Several studies
have documented adverse health effects after exposure to such products. Gloves
made of vinyl or latex are easily penetrated by monomers. Ordinary glasses, or
visors, do not protect against vapour from polymer products. Dental face masks
filter out about 40% of respirable particles. To survey the prevalence of asthma,
atopic dermatitis, conjunctivitis, hay fever/rhinitis, and hand eczema among
dental personnel, a questionnaire was distributed to all dental teams in Northern
Sweden. Referents were researchers, teachers, and secretaries from the same
geographical area. The response rate was 76% for dental teams, and 66% for
referents. The results show a significantly higher prevalence of conjunctivitis,
and atopic dermatitis among dentists, both male and female. Hypersensitivity to
dental materials was reported by significantly more dental personnel than by
referents.
PMID- 9646392
TI - Type of treatment and estimation of time spent on dental trauma--a longitudinal
and retrospective study.
AB - The consequences of traumatic tooth injuries (dental trauma) are time-consuming
and costly treatment and follow-ups, of which our knowledge is scarce.
Consequently the aim of the present study was to measure the total time of
treatment of uncomplicated and complicated traumas to primary and permanent
teeth. The study was performed in three steps based on a randomly selected sample
of Danish children and adolescents living in the municipality of Copenhagen,
Denmark: (I) A descriptive analysis of traumas affecting 106 children and
adolescents all born in 1970 and randomly chosen among the total number of
patients treated. Treatments took place between 1972 and 1988. (II) A study of
the time and frequency of different types of emergency and planned treatment
estimated by 14 dentists employed by the municipal dental service. (III)
Calculation of the total treatment time on the basis of the results from (I) and
(II). The most common traumas were luxations of primary teeth and fractures of
permanent teeth. The most frequent treatments dealt with were uncomplicated crown
fractures and luxations followed by other different diagnoses of complicated
traumas. The treatment time for primary teeth for uncomplicated traumas were used
mostly for information, while the time for complicated traumas was used for
follow-ups. The treatment time for traumas to permanent teeth was dominated by
follow-ups, irrespective of the complication status. Only 3% of uncomplicated
traumas of permanent teeth resulted in endodontic treatment, compared to 67% with
complicated traumas. Uncomplicated traumas to primary teeth required a total of
2.5 visits and 0.8 hrs treatment time, while 4.3 visits and 1.6 hrs per
individual were used for complicated traumas. For permanent teeth with
uncomplicated traumas 9.2 visits and 3.2 hrs were required, and for complicated
traumas 16.4 visits and 8.5 hrs per individual. The respective treatment times
for complicated traumas for primary and permanent teeth were 2.0 and 2.7 times
higher, compared to the corresponding uncomplicated traumas. There were no gender
differences in type of injury and number of visits for injuries to primary and
permanent teeth.
PMID- 9646393
TI - Ethical issues in dental management of patients with severe dementia: ethical
reasoning by hospital dentists. A narrative study.
AB - Dementia alters the patient's ability to accept conventional dental treatment and
conflict situations arise involving moral dilemmans in judgements and actions.
The aim of the study is to disclose how the dentists think, feel and act in such
conflict situations and their ethical reasoning. Qualitative methods are used in
interpretation of 21 tape-recorded narratives from hospital dentists. In all
narratives, the problem emerged from uncertainty about what comprise an
appropriate treatment. The ethical dilemma could either be narrated as internal,
within the dentist or external between the dentist's opinion and opinions to the
contrary from co-actors in the story. In a climate of restraints in public
spending in health care a discourse from the perspectives of ethics is essential
to ensure respect for human integrity in society, fundamental for all caring,
including dental care of patient with dementia.
PMID- 9646394
TI - The Swedish National Dental Insurance's periodontal diagnosis. Used on an
individual level.
AB - The Swedish National Dental Insurance Board requires a periodontal diagnosis (FKF
2030 86.12GR) from general practitioners before treating patients, a process
which is expensive. The Swedish National Dental Insurance-index (SNDI-index) is
based on clinical data and radiographs and every tooth is assigned a rating
between 0 and 4. From the time of introduction of the Swedish National Dental
Insurance plan in 1974, data can have been collected for 1.7 million patients if
the regulations were followed according to the Swedish National Dental Insurance
Board in Stockholm, Sweden. It is of interest to examine whether all of these
collected periodontal data reflect periodontal status. In this study includings
56 individuals, the Swedish National Dental Insurance-index, used on an
individual level, correlated significantly with the individual changes in bone
support (as percent of toothlength) of the tooth in 1979 (rs = -0.80, t = -9.7, p
< 0.001, ci 95% = -0.88(-)-0.68) as well as in 1989 (rs = -0.79, t = -9.5, p <
0.001, ci 95% = -0.87(-)-0.67).
PMID- 9646395
TI - Survival of onlay bone grafts. A study in the adult rat.
PMID- 9646396
TI - On the prosthodontic patient. An investigation of factors influencing patient
expectations and satisfaction with extensive prosthodontic care.
PMID- 9646397
TI - Studies on fluoridated toothpicks.
AB - The aim of this thesis was to evaluate the wooden toothpick as a vehicle for the
delivery of fluoride to the approximal area. After two minutes use in vivo, the
release of fluoride from the pointed section of a toothpick impregnated in 4% NaF
was estimated to 0.15 mg. Toothpicks produced similar or somewhat higher fluoride
concentrations in the approximal area compared with other fluoride-containing
products, like dentifrice, mouthrinse solution and tablet. The mean fluoride
concentration in an approximal area treated for two minutes with a toothpick
impregnated in 4% NaF was around 11 mM/l. Toothpicks impregnated in 4% NaF, 8%
SnF2 or 2% chlorhexidine had an effect on the proportion of mutans streptococci
and on the decline of pH in dental plaque, but it was small and only of short
duration. The recolonization of mutans streptococci was, however, slower after
using the SnF2- and chlorhexidine-impregnated toothpicks than after using the NaF
and non-impregnated toothpicks. The effect of fluoridated toothpicks on the
degree of de- and remineralization of enamel and dentine was measured using
transversal microradiography in an in situ study. Four weeks' use of toothpicks,
especially of NaF-impregnated toothpicks, reduced the degree of demineralization
of enamel and dentine at approximal sites. Secondary ion mass spectrometry was
also used to determine the fluoride content in the outer surface of dentine,
which increased more than 10 times after using fluoride toothpicks compared with
non-impregnated toothpicks. In a second in situ study, 4% NaF-, 2% chlorhexidine-
and non-impregnated toothpicks had a similar effect on sound and demineralized
enamel and on demineralized dentine. However, the NaF toothpicks were superior in
terms of their effect on sound dentine. The effect on mutans streptococci and
plaque-pH, on the other hand, was the same for all three types of toothpicks. The
main conclusion from this thesis is that the wooden toothpick is a suitable
vehicle for the delivery of fluoride to the approximal area.
PMID- 9646398
TI - [Case report. Merino sheep, female, six years old].
PMID- 9646399
TI - [Experiences with a theloresectoscope compared with conventional teat endoscopy
in diagnosis and therapy of covered teat lesions].
AB - In 30 dairy-cows, suffering from a covered teat lesion near the papillar duct
and, as a result, from milk flow hindrance, two different methods of minimal
invasive endoscopy for diagnosis and therapy were performed. In 15 patients
(group I) the endoscope was inserted through the papillar duct and additionally
through an artificial approach in the teat wall. Avulsions of mucosa could be
visualized and resected with special instruments. In further 15 patients (group
II) a new Theloresectoscope (teat-endoscope, combined with integrated
radiosurgery-unit) was used for performance of endoscopy via papillar duct and
lateral endoscopy. Mucosal avulsions were removed under visualization by means of
radiosurgery without inserting an additional instrument through the papillar
duct. Afterwards, after application of antibiotic drugs intramammarily, a natural
teat canal insert (NIT) was administered in the papillar ducts of the 30 treated
teats for seven days to keep the teat canal calm and wide. After three days the
NIT was replaced and antibiosis refreshed. Eight days after endoscopy the
temporary cessation of milking was canceled and the quarters were milked by
machine. In two probands out of group I and three cows out of group II six weeks
after first intervention lateral endoscopy was performed again for documentation
of the healing process. In all 30 cases six weeks after resection of mucosal
avulsions inquiries about the milking-quality were made by phoning the owners of
patients. In 29 cows, still existing on the farms after six weeks, the milking
comfort was considered as being good or, in few cases, satisfactory by the
owners. Somatic cell count showed good results, though eight probands in group I
and nine cows in group II presented positive results in the California-Mastitis
Test. Comparing the two different endoscopic techniques used in this study, both
methods appeared of same value concerning diagnosis of aberrations in bovine teat
by means of endoscopy via teat canal. Differences were found in handling of
instruments performing endoscopy with lateral, artificial approach: the novel
Theloresectoscope is by far more useful in endoscopic surgery, because the
surgical intervention can be performed by a single person, whereas using the
conventional instruments in most cases a second person as an assistant for
operation is required.
PMID- 9646400
TI - [Comparison of two castration methods in cattle: plasma cortisol levels,
leukocyte count and behavioral changes].
AB - Two methods of castration (surgical and Burdizzo method) of male calves were
compared by measuring plasma cortisol concentrations. Increased plasma cortisol
values were found only during the first three hours after castration. There were
no significant differences in plasma cortisol values and changes of behaviour
between groups of surgical and Burdizzo castrated calves. Plasma cortisol values
did not decrease during the first days after castration. The results suggest,
that surgical and Burdizzo-castration do not differ in regard to pain.
PMID- 9646401
TI - [Treatment of acute respiratory tract diseases in cattle with Bisolvon in
combination with either enrofloxacin, cefquinome, ceftiofur or florfenicol].
AB - The purpose of the present clinical studies was to determine the clinical
efficacy of a combined parenteral and oral treatment with Bisolvon in combination
with antibiotics in bovines suffering from acute respiratory disease. To this end
four trials were conducted in respiratory diseased bovines; a total of 619
animals were evaluated. The animals were randomly assigned to one of two
treatment groups within each study and were treated either with enrofloxacin,
cefquinome, ceftiofur or florfenicol. The Bisolvon group was additionally treated
with Bisolvon over 5 consecutive days. Daily clinical examinations were carried
out over a period of 6 days. The clinical respiratory score, the primary
parameter, representing a summation of the scoring points for the parameters
respiratory rate, nasal discharge, spontaneous coughing, lung sounds and grade of
dyspnoea and the clinical index score, which additionally included the general
parameters fever, demeanour and feed intake, were significantly lower in the
Bisolvon groups compared to the controls at all examinations after initiation of
therapy in all trials with the exception of day 2 in one study. Lower values
correspond to a less severe clinical condition. This consistent result as well as
the evaluation of the single parameters are indicative of an acceleration of the
recovery of the animals additionally treated with Bisolvon.
PMID- 9646402
TI - [Investigations on the development of hyponatremia in older calves with
diarrhea].
AB - The study involved 50 hospitalized calves (four weeks to five months old)
suffering from diarrhoea and hyponatraemia (blood sodium concentration below 130
mmol/l). Starting from the day of admission blood, urine, and faecal samples were
taken each morning and sodium and potassium concentrations were measured. In
addition, blood and urine samples were taken in the evenings, if electrolytes had
been given orally during the day. The obtained values from urine samples were
compared with the plasma concentrations in order to check for inadequate renal
excretion of electrolytes. Consistency of the faeces and visible blood admixture
were the main criteria in the evaluation of electrolyte concentration in the 317
samples of faecal water. With one exception no inadequate renal losses of sodium
were observed. Sodium and potassium concentrations in faecal water showed a
distinct negative correlation. As the consistency of faeces grew increasingly
normal, electrolyte contents of faeces approached those reported for adult
cattle, i.e. potassium levels rose and sodium levels decreased. Visible blood
admixtures had no significant effect on the sodium and potassium concentrations
in the faeces. A distinct relationship between electrolyte contents in faecal
water and the consistency of the faeces was found. There were highly significant
differences in electrolyte concentrations between faeces of watery (Na: 82 +/- 21
mmol/l; K: 23 +/- 12 mmol/l) and soupy (Na: 54 +/- 26 mmol/l; K: 42 +/- 19
mmol/l) consistency (mean +/- standard deviation). By contrast, soupy and pulpy
faeces just showed a slight or no difference in electrolyte concentrations. Only
faeces of watery consistency contained approximately as much sodium as observed
in neonatal calf diarrhoea. These results show that the pronounced hyponatraemia
in older calves can hardly be attributed to loss of sodium via faeces and urine.
The following possible causes are proposed: (a) older calves usually have access
to water (therefore there is more gradual dehydration or no dehydration at all);
(b) oral electrolyte solutions are seldom administered.
PMID- 9646403
TI - [Fodder flinging in cattle].
AB - When cattle fling fodder, this is, in many respects, an undesirable behaviour:
fodder is wasted, the interior of the shed is dirtied and the slatted floor is
compromised in its function. Through behavioural observation, it should therefore
be examined which are the determining factors for fodder throwing. Two breeds of
cattle (Simmenthal and Brown Swiss) were examined to establish how often the
animals fling fodder within 60 minutes in the medium-tie-stall and the short-tie
stall system and receiving varied feeding (green fodder and grass silage). Fodder
throwing occurs amongst the two examined breeds, in both housing systems and
amongst animals of all ages. The percentage of fodder flinging of Simmenthal cows
was higher in the medium-tie-stall than in the short-tie-stall system (16.8% and
8.3%; p < 0.01). During the initial period following the start of feeding, the
throwing frequency was at its highest. Fodder throwing animals had a
significantly higher blinking frequency (a sign of excitement) than those not
flinging fodder (p < 0.01). The reasons for food flinging and its possible
effects on the fodder were not checked. Nevertheless, consideration was given to
the meaning of this behaviour pattern. It would seem it is not a behaviour
disorder. It could be that food flinging is the result of a learning process to
control an itch caused by the husbandry system.
PMID- 9646404
TI - [Comparative histological investigations on the teats of sheep and goats].
AB - In the present study the teats of the goat and the sheep were investigated light
microscopically. In both species, smooth muscle elements condense towards the
streak canal, and abundant arteries occur with thick tunica media and various
valve structures. The apocrine sweat gland have a wide acinous element, which are
regarded as a part of the excretory duct. Additional alveolar secretory tissue is
present in the wall of the lactiferous sinus, which tubuloalveoli are probably of
two varying types in the sheep and empty directly into the lumen of the
lactiferous sinus in the goat. The histologic features of the teat in the goat
differ mainly in the smaller and less coiled apocrine sweat glands, the thin
stratum granulosum of the teat canal epithelium and the occurrence of
supplementary canals (frequently two) in the initial part of the teat canal. The
ovine teat shows a partly extremely thin epidermis, solid coiled apocrine sweat
glands, and a pigmented epithelium of the teat canal equipped with a considerably
thicker stratum granulosum.
PMID- 9646405
TI - [Halicephalobus (Syn. Micronema) deletrix as a cause of granulomatous gingivitis
and osteomyelitis in a horse].
AB - Therapy resistant swellings of the maxillary region and unilateral nasal
discharge in older horses are mainly thought to be consequences of neoplasias of
the oral cavity, especially of the gingiva and the teeth, or to develop from
tumours of the nasal cavity. We report an unilateral swelling of the left nasal
and buccal region in a 13-year-old gelding, which was accompanied by an
aggressive destruction of involved osseous tissue due to a severe proliferative
granulomatous inflammation. The granuloma was caused by the nematode
Halicephalobus (syn. Micronema) deletrix. This nematode infection is known for
over 30 years, even though the here reported form is uncommon and rarely
diagnosed. However, this report shows that even in cases of unilateral maxillary
swellings in horses a granulomatous inflammation due to nematodiasis should be
considered as an additional differential diagnosis.
PMID- 9646406
TI - [Investigation of hematologic and clinical chemical parameters in serum of
newborn fallow deer calves (Dama dama L.). Clinical chemical parameters].
AB - 59 blood samples from newborn fallow deer calves were clinical-chemically
investigated at day of birth. To estimate the metabolic situation post natum we
measured the concentration of glucose (6.8 +/- 2.2 mmol/l), total protein (54.0
+/- 8.7 g/l), albumin (19.5 +/- 2.3 g/l), gammaglobulins (3.5 +/- 2.0 g/l), urea
(5.2 +/- 1.8 mmol/l), creatinine (86.2 +/- 22.8 mumol/l) and bilirubin (4.4 +/-
4.4 mumol/l). Furthermore the activity of the enzymes AP (3258 U/l), ALAT (10.8
U/)l, ASAT (67.2 U/l), GGT (82.2 U/l) and CK (181.0 U/l) was measured.
Additionally following minerals were determined: sodium (135.8 +/- 10.2 mmol/l),
chloride (95.6 +/- 7.5 mmol/l), potassium (4.3 +/- 0.6 mmol/l), calcium (2.6 +/-
0.3 mmol/l), inorganic phosphor (2.4 +/- 0.5 mmol/l) and iron (12.1 +/- 8.0
mumol/l).
PMID- 9646407
TI - [Preliminary examinations on the effects of the breed characteristic feature
"feather crest" on skull and brain anatomy of domestic ducks (Anas platyrhynchos
f. dom.)].
AB - As mentioned in older sources, the crested breed of the domestic duck is
described as variety with high pre- and postnatal mortalities, malformations in
skull and brain anatomy, and several central nervous deficiencies in affected
birds. Therefore this breed is to be called defective and abnormal in the sense
of section 11b of the German protection of animals legislation. Poultry fanciers
reject these findings as incorrect, but accurate scientific examinations that
bear out this allegation are not available. Preliminary examinations have
demonstrated that brain and skull anatomy of living animals can be described by
using non-invasive diagnostic techniques (magnet-resonance-imaging, computerized
tomography, radiography). The use of this progressive methods enables to
expressive findings on present stocks of domestic ducks. Many of the test animals
investigated in preliminary examinations by using magnet-resonance-imaging and
radiography showed abnormal tissue deposits in the tentorium cerebelli, meningo
encephalocele, cranial malformations, and variable bone formations in the
thickened hypodermis of the crest. If crested ducks are mated against each other,
numerous offspring show malformations of upper beak and cranium, encephalocele,
as well as craniopagal parasites in form of rudimentary legs.
PMID- 9646408
TI - [Changes in pharmaceutical market 1996/1997].
PMID- 9646409
TI - [Relevance of Helicobacter pylori infection in the development of gastric
tumors].
AB - Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer
disease. Besides, epidemiological studies indicate that helicobacter may be
involved in the development of gastric cancer and MALT-lymphoma by inducing
gastritis and accumulation of lymph follicles in the gastric mucosa. The
carcinogenic effect of helicobacter pylori can be explained by various
pathogenetic factors which are produced by the bacterium itself. Furthermore,
influences of helicobacter pylori on the vitamin C content of gastric mucosa
might play a role. Currently, Hp-eradication therapies for the treatment of
gastric MALT lymphomas are already under investigation in controlled studies.
Concerning gastric cancer prevention, however, the available data are not
sufficient to warrant a general recommendation for eradication-therapies of all
Hp-infected persons. However, further studies must show whether Hp-eradication of
high-risk subjects, i.e. members of gastric cancer families, young patients with
chronic-active gastritis or with chronic-atrophic gastritis and intestinal
metaplasia, are effective in reducing gastric cancer risk.
PMID- 9646410
TI - [Case report. Rough haired dachshund, male, 13 years].
PMID- 9646411
TI - [Hazardous material and safety conditions in veterinary practice. 2: Flammable
liquid, disinfectants and cleansing media, cytostatics, pressurized gases, liquid
nitrogen, narcotic gases, mailing of diagnostic samples, hazardous waste].
AB - In the last years the standards for professional handling of hazardous material
as well as health and safety in the veterinary practice became considerably more
stringent. This is expressed in various safety regulations, particularly the
decree of hazardous material and the legislative directives concerning health and
safety at work. In part 1, a definition based on the law for hazardous material
was given and the potential risks were mentioned. The correct documentation
regarding the protection of personal and the purchase, storage, working
conditions and removal of hazardous material was explained. General rules for the
handling of hazardous material were described. In part 2, partial emphasis is put
on the handling of flammable liquids, disinfectants, cytostatica, pressurised
gases, liquid nitrogen, narcotics, mailing of potentially infectious material and
safe disposal of hazardous waste. Advice about possible unrecognized hazards and
references are also given.
PMID- 9646412
TI - [Ophthalmology quiz. Free pigmented iris cyst in anterior ocular chamber].
PMID- 9646413
TI - [Feasibility of sonography in the diagnosis of congenital heart diseases in
dogs].
AB - In ultrasound examination of the heart it is useful to combine the following
techniques: echocardiography (in 2D and M-mode) gives information about
morphology and motion of the heart. By using Doppler echocardiography (black and
white or preferably colour) it is possible to evaluate bloodstreams and with
contrast echocardiography shunts in the heart can be demonstrated. In our study
(1994-1996) the following congenital heart defects were the most common in dogs:
subaortic stenosis (SAS, 41%), pulmonic stenosis (PS, 19%), patent ductus
arteriosus (PDA, 11%) and the combination of subaortic stenosis with pulmonic
stenosis (11%). Echocardiography allows the morphologic evaluation of the primary
defect in detail, for example the differentiation between aortic valve stenosis
and subaortic stenosis. However the exact identification of the patent ductus
arterious and of the morphology in pulmonic stenosis can remain difficult,
especially in patients showing dyspnoe. In heart sonography quantitative
measurements are available to graduate the defects, but guidelines for these
measurements are not yet defined. The demonstration of secondary and combined
defects, which are important for therapy is easily possible with heart ultrasound
examination. Secondary insufficiencies are often seen at the mitral valve because
of primary subaortic stenosis or patent ductus arteriosus and at the tricuspid
valve because of pulmonic stenosis. For differentiation of combined heart defects
(SAS with PS; SAS with PDA; PS with atrium septum defect) heart ultrasound is
extremely valuable.
PMID- 9646414
TI - [Diabetes mellitus in young dogs and cats. Case reports and a comparison with
relevant literature].
AB - Cases of diabetes mellitus in young cats and dogs (younger than five years) are
described rarely in contrary to reports in older patients (older than eight
years). Histological alterations of pancreatic islets in young canine and feline
diabetic patients represent the main issue of this publication together with the
regenerative capacity of insulin-producing cells in these patients. These
regenerative phenomenons of differentiated islet cells (replication) or their
progenitors (neogenesis deriving from stem cells) are detected in young cats and
dogs in isolated cases whereas they are in general missing in older patients. In
this publication, own cases are presented together with histopathological as well
as clinical findings. The cases are discussed with the relevant literature of
veterinary and human medicine.
PMID- 9646415
TI - [Idiopathic mucinosis cutis in Chinese Shar pei dogs: epidemiology, clinical
features, histopathologic findings and treatment].
AB - Species specific diseases, e.g. idiopathic mucinosis of the Chinese Shar Pei are
reported by use of 31 clinical cases and 140 biopsy samples. Idiopathic mucinosis
is one of the most frequent diseases of this increasing breed in Germany, too.
The disease is diagnosed by use of histologic examination of skin biopsies.
Therapy is performed by application of corticosteroids and symptomatic treatment.
PMID- 9646416
TI - [Dog tourism and import: an inquiry in Germany on the extent as well as on the
spectrum and preference of countries of residence and origin respectively].
AB - A survey was conducted among practicing veterinarians and at pet clinics in
Germany in order to estimate the extent of tourism with dogs and import of dogs
and to determine the range and preference of the foreign countries involved. The
survey covered the years from 1985 to 1995 and included 5240 dogs, of which 4567
(87.2%) were born in Germany and 673 (12.8%) were born abroad. Among the latter,
263 (39.1%) originated from Mediterranean countries and Portugal, 344 (51.1%)
were born in other European countries and 66 (9.8%) were from non-European
countries. Of all 5240 dogs surveyed, 2894 (55.2%) had been taken abroad at least
once between 1985 and 1995. Of these, 2424 (53.1%) were born in Germany, 470
(69.8%) were born abroad. Of the 2894 dogs taken abroad, 1929 (66.7%) travelled
to Mediterranean countries or Portugal and 1152 of these had additional travels
to other countries as well. The spectrum of all countries travelled to was very
broad, but numerous dogs were taken regularly, repeatedly and exclusively to
Austria, Switzerland, Italy, Spain or France. Other countries were visited only
once for the majority of dogs. The analysis of the annual survey data revealed a
steady increase of dogs along on trips from Germany to other countries, rising
from 31.1% in 1990 to 40.8% in 1994. In any of these years, always more than 56%
of these dogs were taken to Mediterranean countries.
PMID- 9646417
TI - [Eye diseases in dwarf rabbits. 1. Anatomy, investigation procedures, diseases of
the eyelid, the conjunctiva and the nasolacrimal duct].
AB - The clinical ophthalmology of dwarf rabbits is reviewed in this continuing
article. The first part contains the ophthalmological examination scheme and
anatomical features of the rabbit's eye. Furthermore diseases of the eyelids,
conjunctiva and of the nasolacrimal duct are described. These are illustrated by
means of selected photographs.
PMID- 9646418
TI - [Comparative investigations on inhalation anesthesia with isoflurane (Forene) and
sevoflurane (SEVOrane) in racing pigeons (Columba livia Gmel., 1789, var.
domestica) and presentation of a reference anesthesia protocol for birds].
AB - A conventional inhalation anaesthesia using an isoflurane and sevoflurane-oxygen
nitrous oxide-mixture was performed in each six domestic pigeons (Columbia livia
Gmel., 1789, var. domestica). Over a period of 60 minutes routine anaesthetic
monitoring including reflex score (12 reflexes, cloacal body temperature and
pulse oximetry) was performed. For anaesthesia maintainance 4.0 +/- 0.3 Vol. %
sevoflurane compared to 2.0 +/- 0.2 Vol. % isoflurane were used. The induction
period using sevoflurane was shorter (95 +/- 9 sec) than by using isoflurane (154
+/- 12 sec). The recovery period was significantly shortened using sevoflurane
(162 +/- 12 sec) compared to isoflurane with 186 +/- 12 sec. Results show, that
the use of sevoflurane is indicated especially in patients bearing anaesthesia
risks, but has a number of advantages, though anaesthetic potency is
approximately 50% lower than in isoflurane, causing higher costs. Furthermore low
toxicity of sevoflurane leads to a lower burden for the surgical staff through so
called "waste gases", which play an important role in avian anaesthesia using a
head chamber for application. Beside a review on current techniques in avian
anaesthesia this paper includes a standardised detailed anaesthesia protocol
description of avian inhalation anaesthesia regarding the technical equipment as
well as its practice, which allows an exact documentation of the anaesthetic,
meeting legal requirements, too. The results show that inhalation anaesthesia
with isoflurane or sevoflurane has to be preferred even in birds when compared to
ketamine anaesthesia, the future use of which has to be restricted to sedation
and immobilisation partly due to animal welfare grounds.
PMID- 9646419
TI - [Therapy of varicocele].
PMID- 9646420
TI - Pathophysiological effect of varicocele treatment.
PMID- 9646421
TI - [Effects of varicocele therapy on spermatozoan function].
AB - Men suffering from varicocele have lower mean sperm counts and "worse" seminal
parameters than those without a varicocele. Also in those with a varicocele, who
already fathered a child, the mean sperm count is lower than in other fertile
men. The observations, however, do not refer specifically to an existing
varicocele, but are common also in other spermatogenic defects. This holds also
true for the frequency of tapering forms. Besides the classical parameters of the
spermatozoa also novel parameters of the extended semen analysis were tested. As
well in the rate of acrosome-reacting spermatozoa, in the rate of anilinblue
stained cells, in the number of zona binding-spermatozoa as in the concentration
of sperm antibodies no differences between men with and men without a varicocele
were found. The grade of a varicocele does not account for the degree of the
spermatogenic defect. The progressive damage to the spermatogenesis by an
persisting varicocele is discussed controversely. It was suggested that an early
treatment of a varicocele, in particular in the adolescence, might inhibit the
later insufficiency of sperm production. Correction of a varicocele is followed
by an improvement of seminal parameters, in particular of sperm motility. In
controlled studies, however, this effect was also observed in the untreated
group. This casts some doubt on the causative effect of the varicocele treatment.
The improvement of seminal parameters is not always accompanied by an increase in
fertility, although also some functional parameters showed an improvement after
correction of the varicocele.
PMID- 9646422
TI - Varicocele: does treatment promote male fertility?
PMID- 9646423
TI - [Treatment of varicocele in the age of "evidence-based medicine". Medical
counseling is as successful as interventional treatment (ligation or
embolization)].
AB - In the age of "evidence-based medicine" the results of controlled clinical trials
form the basis of therapeutic decisions. Until recently, interventional treatment
has been the routine therapy for an infertile man with varicocele. However,
recent controlled studies have shown that intensive counselling of the infertile
couples results in as many pregnancies as ligation of embolization of the
spermatic vein. Therefore, the traditional treatment regimen for varicocele
should be reconsidered and the pathophysiology of the varicocele should be
elucidated to provide a basis for rational treatment.
PMID- 9646424
TI - [A critical analysis of studies of varicocele therapy from the biostatistics
viewpoint].
AB - Since approximately 45 years subfertile patients with varicocele are treated with
different techniques of a varicocelectomy if there are no (other) causes of
infertility. In the meantime, a varicocelectomy is being applied prophylactically
in adolescents, too. In this article, there should be investigated whether the
conducted clinical trials provide evidence of the efficacy of a varicocelectomy.
Due to the fact that there are only a few valuable trials concerning the therapy
of varicocele, the meta-analysis is mainly a critical analysis of the considered
biostatistical methods. It comes to the conclusion that there is no clinical
evidence for efficacy as well as against, and this conclusion is valid for the
treatment as well as for the prophylaxis of male factor infertility. To achieve
evidence, intensification of cooperation in multicenter study groups is necessary
and methodical quality of the clinical trials on varicocelectomy should be
improved.
PMID- 9646425
TI - [Therapy of varicocele. Attempt at assessment of current status].
PMID- 9646426
TI - [Mycophenolate mofetil (MMF) for prevention of kidney transplant rejection. A new
immunosuppressive agent. International Mycophenolate Mofetil Study Group].
AB - 1493 patients were enrolled in 55 centers in Europe, Canada, Australia and the
USA comparing the efficacy of mycophenolate mofetil (MMF) in daily doses of 2 and
3 g with placebo/azathioprine (PLA/AZA) for the prevention of acute rejection in
renal transplant patients. Acute rejections and graft loss and death at 1 year
were measured per trial and these data were combined and analyzed in a pooled
fashion. The three pooled treatment groups were well balanced regarding
demographic characteristics and cause of renal failure leading to
transplantation. At one year the graft survival rate was 90.4% and 89.2% in the
MMF 2 g and 3 g groups compared with 87.6% in the PLA/AZA-group. MMF 2 and 3 g
were significantly better than PLA/AZA in reducing biopsy proven rejection at one
year: 40.8% placebo/aza vs. 19.8% in the MMF 2 g group and 16.5% in the MMF 3 g
group.
PMID- 9646427
TI - [Provocation of corpus cavernosum EMG signals as a parameter in diagnosis of
erectile dysfunction].
AB - Parameters of CC-EMG able to distingiush between healthy controls and men with
erectile dysfunction of different etiology in the individual case are currently
unknown. Groups of healthy volunteers and men with erectile dysfunction however
show significant differences in provocability of slow cavernous electric
activity, i.e. if so called "typical single potentials" (tSP) can be recorded
already under resting conditions, or only with provocation, or if any activity is
missing. In men, who showed tSP already under resting conditions, a significantly
higher extent of provoked activity could be assessed as in those, who showed tSP
only after provocation. This applies to the number as well as for the extent of
the responses to the 3 stimuli valsalva-manoeuvre, arousal and hyperventilation.
Patients, who had shown tSP already under resting conditions, were similar to the
controls, from whom those, who showed tSP exclusively with provocation differed
significantly. Further research will have to prove, if the parameter
"provocability" together with the parameter "extent of the provoked cavernous
electric activity" might be able to to lead to a better distinction of healthy
and pathological situations which would be a precondition for the introduction of
the method into clinical use.
PMID- 9646428
TI - [Lymphocyte transformation test (LTT) as a model for evaluating cytokine-induced
immunomodulation in renal cell carcinoma].
AB - We investigated the immunomodulatory capacity of cytokines produced by renal cell
carcinoma in vitro by analyzing their effects on mitogen-induced T-lymphocyte
blast cell transformation. All of the tested 70 cell cultures, derived from 70
tumor areas in 33 patients, had immunomodulatory capacity. In addition to
suppression in the lymphocyte transformation test (max. 44/70; 63%) there was
also superinduction (max. 37/70; 53%). We found no significant correlation with
the stage and grade of primary tumors. However, the suppression of mitogen
induced T-lymphocyte blast cell transformation was significant in multifocal
tumors (0.08% TCM, P < 0.001) and non-significant in metastatic tumors. The
production of the assayed cytokines IL-6, IL-10, IL-11, and TGF beta 1 was
variable and there was no significant correlation to the immunomodulatory
capacity of the tumors.
PMID- 9646429
TI - [Prognostic relevance of vena cava thrombosis in renal cell carcinoma].
AB - The independent prognostic value of neoplastic extension of renal cell cancer
(RCC) into the vena cava inferior has been the subject of several investigations
reported to date. However, the use of vena cava thrombosis as an independent
prognosticator of a patient's long-term survival is still debated. We have
therefore correlated the clinical course of 53 patients with RCC and vena cava
thrombosis with a control group consisting of 47 patients with renal cell tumors
without vena cava thrombosis (follow-up: 1-154 months). The median long-term
survival of patients with and without vena cava thrombosis was 32 and 35 months,
respectively. Neither the propagation of the tumor into the vena cava (P = 0.391)
nor the cranial extension of the thrombosis (P = 0.158)--even in case of
propagation into the right atrium--could be identified as parameters of any
prognostic value during univariate or multivariate statistical analysis.
PMID- 9646430
TI - [Collagen metabolism in induratio penis plastica (IPP)].
AB - The exact pathogenesis of Peyronie's Disease (PD) is still unknown.
Histopathological investigations suggest, that the metabolism of the collogenious
tissue plays an important role. Therefore, we started a prospective study in
order to evaluate the metabolic situation of 11 patients with PD and 11 healthy
controls. We measured biochemical parameters of penile and venous blood, which
correspond to the collagen metabolism (procollagen III [P III P], PMN-elastase
[PMN-E], fibronectin [FN], fibronectinreceptor [FN-R] und alpha-1-proteinase
inhibitor [alpha-1-PI]). There was no difference in PMN-E, P III P, FN and FN-R
in all samples. There was no difference in penile and venous blood as well. But
we found out a highly significant lower concentration of alpha-1-PI in patients
with PD (158,55 mg/dl) than in controls (214,82 mg/ dl). A deficiency of alpha-1
PI can lead to a higher activity of serum proteases, such as PMN-E. This can
result in a change in collagen metabolism by an increased synthesis of collagen
type III, that is found in PD. This general pathophysiologic factor may be
competed by an additional local alteration of the tissue.
PMID- 9646431
TI - [Paraneoplastic syndromes].
PMID- 9646432
TI - [Kidney parenchyma carcinoma--diagnosis. German Society of Urology].
PMID- 9646433
TI - [Para-spinal regional anesthesia and prevention of
thromboembolism/anticoagulation. Recommendations of the German Society of
Anesthesiology and Intensive Care Medicine, October 1997].
PMID- 9646434
TI - Modulation of T cell and monocyte function in the spleen following infection of
pigs with African swine fever virus.
AB - Infection of pigs with many strains of African Swine Fever Virus (ASFV) has been
shown to cause a loss or marked decrease in the ability of splenocytes to respond
to mitogens. These observations have been extended by cell fractionation and
reconstitution experiments to show that the mitogen stimulated proliferative
capacity of both the CD4+ and CD8+ T cells is affected. Similarly, monocytes
which are directly infectable by virus, are functionally defective as antigen
presenting cells when added to mitogen stimulated normal T cells. Interestingly,
the same T cells which respond poorly in mitogenic assays can be activated by
stimulation through the CD3 receptor. In contrast to the defective mitogenic
response of T cells, B cell function, as assessed by stimulation through the CD40
ligand in vitro remains intact. There is no evidence for apoptosis in either the
T cells or the B cells recovered from the spleens of ASFV infected animals 1-5
days following infection. Although the number of leucocytes which can be
recovered from the infected spleen decreases rapidly with progression of the
disease, the proportion of the different cell phenotypes remains constant. Thus
decreased activity of lymphocytes in lymphoid tissue from ASFV infected animals
appears to be directly attributable to infection of the monocytes.
PMID- 9646435
TI - Tumor necrosis factor and interferon activity in the circulation of calves after
repeated injection of low doses of lipopolysaccharide.
AB - The effect of two intravenous (i.v.) injections of low doses of
lipopolysaccharide (LPS)(0.1 microgram/kg of body weight) administered at 7-day
intervals on the systemic release of tumor necrosis factor (TNF) and interferon
(IFN), on the rectal temperature, breathing and heart rate, and on packed cell
volume (PCV), plasma glucose concentration, white blood cell (WBC) counts in 3
week-old calves, was estimated. The first injection of LPS caused a significant
increase in breathing and heart rate, rectal temperature, prolonged hypoglycemia
and leukopenia, but no significant changes in PCV were observed. TNF and IFN
activity peaked at 2 h after LPS injection and disappeared from circulation by 4
h and 5 h, respectively. After the second injection of LPS, the reaction of
calves was similar to that observed after the first injection, however, the
breathing rate and TNF systemic production were significantly reduced. The
results obtained indicate that a low dose of LPS leads to the development of
'late' tolerance manifested by hyporeactivity to TNF production but with
maintained responsivity to IFN production, pyrogenic, hypoglycemic and leukemic
response to the second injection of LPS. In conclusion, these results demonstrate
that the tolerance response is not universal to all hematologic and immunologic
parameters, and that the response needs to be evaluated with respect to the
specific variable.
PMID- 9646436
TI - Compensation of preliminary blood phagocyte immaturity in the newborn calf.
AB - To estimate the functional maturity of the phagocytic defence in neonatal calves,
we analyzed the characteristics of blood phagocytes from calves (n = 10) 1 h post
partum (p.p.) and 4 h p.p. At 1 h p.p., all calves were colostrum-deprived, while
5 calves had received colostrum before the 4 h p.p. sampling. The results were
compared to those obtained from 3-9-week-old calves (n = 10). Phagocytic and
oxidative burst activity of polymorphonuclear leukocytes (PMNL) and monocytes
were determined in whole blood and separately analyzed by flow cytometry. In
neonates prior to colostrum ingestion (1 h p.p.), phagocytic activity of PMNL
against non-preopsonized E. coli was lower when compared to PMNL of 3-9-week-old
calves. Opsonization of bacteria with pooled plasma from adult animals only
partially restituted this lower PMNL phagocytic activity, indicating that humoral
as well as cellular aspects of PMNL phagocytosis are altered in neonatal calves.
In contrast to PMNL, monocytes of neonates exhibited an enhanced phagocytic
activity. The oxidative burst activity of PMNL, as well as of monocytes was
higher in newborn calves. During the first 4 h of life, the activities of blood
phagocytes changed. Colostrum ingestion was accompanied by an increase in the
percentage of phagocytizing PMNL and monocytes. This increase was absent in
colostrum-deprived calves. In contrast, the oxidative burst activity of
phagocytes decreased with age. In monocytes, the decrease of oxidative burst
activity was only observed in colostrum-fed calves. In conclusion, some blood
phagocyte functions in calves were found to be immature at birth, but these
functions are presumably compensated by high absolute PMNL numbers and by other
the more active mechanisms.
PMID- 9646437
TI - Comparative morphofunctional study of dispersed mature canine cutaneous mast
cells and BR cells, a poorly differentiated mast cell line from a dog
subcutaneous mastocytoma.
AB - The dog mastocytoma BR cell line provides us with a permanent source of canine
mast cells, allowing a characterization of secretory mediators that exert
important effects in canine allergic and nonallergic diseases and in
physiological processes. We studied the ultrastructural characteristics and
histamine releasing activity after immunological and non-immunological stimuli of
the dog mastocytoma BR cell line, and compared the cell line to normal skin mast
cells enzymatically isolated from healthy dogs. The histamine content of BR cells
was 0.04 +/- 0.002 pg/cell, approximately 100-fold less than that found in canine
skin mast cells. Non-immunologic stimuli induced similar concentration-dependent
histamine release from skin mast cells and BR cells: 29.3 +/- 0.9% vs. 12.7 +/-
0.7% (calcium ionophore A23187), 23.3 +/- 0.7% vs. 18.8 +/- 0.7% (substance P)
and 12.5 +/- 0.3% vs. 12.1 +/- 0.9% (compound 48/80), respectively. Immunologic
stimulation, however, was only effective on canine skin mast cells, causing 30.9
+/- 1.7%, 27.7 +/- 0.6% and 12.2 +/- 0.9% histamine release in response to anti
canine IgE, concanavalin A, and antigen Asc S 1, respectively. The absence of
functional IgE receptors in BR cells was confirmed by the lack of response to
anti-IgE and antigen Asc S 1 following passive sensitization with dog atopic
serum and dog antigen sensitized serum. We conclude that BR cells are able to
release histamine after non-immunologic stimulation in a similar manner to canine
skin mast cells, but that there are morphological and functional differences
possibly due to different states of maturity or differentiation. For this reason
the study of the highly homogeneous BR cells could offer insights into dog mast
cell biology in contexts where freshly isolated cells cannot be used because of
low purity and recovery.
PMID- 9646438
TI - CD4, CD8 and TCR defined T-cell subsets in thymus and spleen of 2- and 7-week old
commercial broiler chickens.
AB - To better understand immune development and function in meat-type chickens
(broilers), the proportions of T-cells expressing CD4, CD8, and T-cell receptors
(TCR) in the thymus and spleen were determined by three-color fluorescence and
flow cytometry in 2- and 7-week old broilers raised in commercial growing
conditions. Broiler thymocytes consisted of single-(CD4+CD8- and CD4-CD8+) and
double-(CD4+CD8+) positive subpopulations. Within these CD4+ and/or CD8+
thymocyte populations, all types of TCR (y delta, V beta 1 alpha beta, and V beta
2 alpha beta) could be identified. In the thymus, percentages of CD4+CD8- cells
increased, CD4-CD8+ cells remained unchanged, and CD4+CD8+ cells decreased
between 2 and 7 weeks of age. In the spleen, in addition to single-positive
lymphocytes, double-positive populations were identified, expressing either y
delta or alpha beta TCR. The percentage of CD4+CD8- splenocytes decreased, and
the percentages of both CD4-CD8+ and CD4+CD8+ splenocytes increased between 2 and
7 weeks of age. Age-associated shifts in TCR usage (the proportion of cells
expressing a certain type of TCR) were observed in the single-positive, but not
in the double-positive, T-cell populations of both thymus and spleen. This
multiparameter cell population analysis in broilers demonstrates thymic and
splenic T-cell subsets similar to those previously described in layers.
Differences in the proportions among T-cell subsets between 2- and 7-week old
broilers likely reflect a more competent immune system in the older birds.
PMID- 9646439
TI - In vitro effects of the extracellular protein of Renibacterium salmoninarum on
phagocyte function in brook trout (Salvelinus fontinalis).
AB - Renibacterium salmoninarum is a facultative intracellular pathogen often found in
host phagocytes where it appears to successfully avoid the host fish's
immunological defenses. The objective of this investigation was to determine if
soluble extracellular protein (ECP) produced by R. salmoninarum may contribute to
the immunomodulation in bacterial kidney disease (BKD) via inhibition of
phagocyte respiratory burst and/or phagocytosis mechanisms. Splenic cells from
adult brook trout (Salvelinus fontinalis) were incubated with two different
concentrations of ECP (0.1 mg/ml and 1.0 mg/ml) and viable R. salmoninarum.
Splenic cell cultures were evaluated for respiratory burst activity via flow
cytometry with the dichlorofluorescin diacetate (DCF-DA) assay and for
phagocytosis via light microscopic assessment of microsphere engulfment.
Respiratory burst activity was significantly inhibited in all treatment groups as
compared to untreated fish, while no differences were noted in phagocytic
activity.
PMID- 9646440
TI - In vitro interaction of viral haemorrhagic septicaemia virus and leukocytes from
trout (Oncorhynchus mykiss) and turbot (Scophthalmus maximus).
AB - Viral haemorrhagic septicaemia virus (VHSV), a well known salmonids pathogen, has
also been reported to be pathogenic for turbot (Scophthalmus maximus). In the
present work, the replication of VHSV was studied in vitro in turbot head kidney
macrophages and blood leukocytes. VHSV was able to infect both primary cultures
and viral titer increased with time, either inside the cells or in the
supernatant. However, no cytopathic effect was observed during the experiments
and the titers were always lower than those obtained in the fish cell lines. The
number of trout and turbot macrophages after several days of in vitro infection
with VHSV was compared with uninfected controls by viable cell count but no
significant differences were observed. The number of cells supporting viral
replication evaluated by immunofluorescence in trout and turbot was low (8 and
1.7%, respectively). Respiratory burst activity of head kidney macrophages was
assayed at different days post-infection, but no significant differences were
found between the control and the infected cultures neither in trout nor turbot.
PMID- 9646441
TI - Reactivation of latent bovine herpesvirus 1 in cattle seronegative to
glycoproteins gB and gE.
AB - Six heifers were vaccinated intranasally with the live bovine herpesvirus 1
(BHV1) temperature-sensitive (ts) vaccine strain RBL106 within 3 weeks of birth.
These calves most likely still had maternal antibodies against BHV1. Thereafter,
these heifers were vaccinated several times with an experimental BHV1
glycoprotein-D (gD) subunit vaccine. At the age of 3 years these 6 heifers were
seronegative in the BHV1 gB and gE blocking ELISAs, but had neutralizing
antibodies against BHV1, probably induced by the vaccinations with the gD subunit
vaccine. Five of these 6 heifers excreted BHV1 after treatment with
dexamethasone. Restriction enzyme analysis of the genome of the excreted viruses
revealed that all 5 isolates had a BHV1.1 genotype and that isolates of 3 heifers
were not obviously different from the ts-vaccine strain. The restriction enzyme
fragment pattern of the isolate of 1 heifer was clearly different from the
pattern of the ts-vaccine strain. It is concluded that cattle can be seronegative
against BHV1 gB and gE but can still carry BHV1 in a latent form. This finding
strongly suggests that there are completely BHV1 seronegative cattle that are
latently infected with BHV1. The impact of this finding on BHV1 eradication
programmes is discussed.
PMID- 9646442
TI - Aujeszky's disease (pseudorabies) virus detection in cerebrospinal fluid in
experimentally infected pigs.
AB - The presence of Aujeszky's disease virus in cerebrospinal fluid of experimentally
infected pigs was studied using the techniques of virus isolation and PCR. Pigs,
some of which were previously vaccinated against Aujeszky's disease, were
inoculated with different doses of the Aujeszky's disease NIA-3 strain. At the
time of death or sacrifice, a sample of cerebrospinal fluid was taken and tested
for the presence of virus using the mentioned techniques. Virus was isolated only
from one sample, while it was detected by PCR in most of them. The higher
sensitivity of the PCR technique and the possible presence of antiviral
antibodies in the cerebrospinal fluid are reasons that can be argued to explain
this fact. By PCR, the virus was detected more efficiently when digested
cerebrospinal fluid cells were used as DNA source than when using whole
cerebrospinal fluid, suggesting that the virus could be cell-associated.
Aujeszky's disease virus could not be detected by PCR in pigs which survived the
acute phase of the infection and were euthanased at 8 weeks post-inoculation,
when they were latently infected. This indicated that the cerebrospinal fluid is
not an adequate sample for the diagnosis of latency. Since Aujeszky's disease
virus was detected from most of the tested samples, we believe that this could be
an adequate procedure for the quick diagnosis of Aujeszky's disease.
PMID- 9646443
TI - Suppression of pseudorabies virus replication by a mutant form of immediate-early
protein IE180 repressing the viral gene transcription.
AB - A mutant form of the immediate-early (IE) protein IE180 of pseudorabies virus
(PRV), dIN454-C1081 is a strong repressor of the PRV IE gene promoter. In order
to assess the antiviral potential of the IE180 mutant, HeLa cells were
transformed with the mutant gene and then infected with PRV and herpes simplex
virus type 1 (HSV-1). The transformed cell lines showed marked resistance to PRV
infection, but were susceptible to infection with HSV-1, indicating that the
IE180 mutant expressed in the stable cell line specifically inhibited PRV growth.
In those cells infected with PRV, transcription of the PRV IE gene was repressed.
In addition, the IE180 mutant exhibited a dominant-negative property in transient
expression assay. The present results indicate that the resistance of the cells
to PRV infection was due to repression of the IE gene transcription by the IE 180
mutant.
PMID- 9646444
TI - Detection of canine oral papillomavirus-DNA in canine oral squamous cell
carcinomas and p53 overexpressing skin papillomas of the dog using the polymerase
chain reaction and non-radioactive in situ hybridization.
AB - Nineteen cutaneous and mucocutaneous papillomas, as well as 29 oral and 25 non
oral squamous cell carcinomas of dogs were analyzed immunohistologically for the
presence of papillomavirus (PV)-antigens. Canine oral papillomavirus (COPV)-DNA
was detected in formalin-fixed, paraffin-embedded tissues by polymerase chain
reaction (PCR) and non-radioactive in situ hybridization (ISH). Furthermore, the
expression of the tumor suppressor protein p53 was investigated. PV-antigens were
detectable in more than 50% of the oral and cutaneous papillomas, while no PV
antigens could be demonstrated in venereal papillomas. One squamous cell
carcinoma was PV-antigen positive. Only two cutaneous papillomas of the head
showed a strong p53-specific immunostaining, while overexpressed p53 was
detectable in approximately 35% of all squamous cell carcinomas. It was possible
to amplify fragments of the E6, E7 and L1 gene by polymerase chain reaction (PCR)
from five of eight oral and from five of eight cutaneous papillomas as well as
from three oral squamous cell carcinomas. Nine of 10 papillomas showed a strong
nucleus-associated hybridization signal typical for COPV-DNA. In three squamous
cell carcinomas COPV-DNA was located in nests of the epithelial tumor cells
surrounding 'horn pearls' or disseminated in the carcinoma tissue. These
observations support the view that COPV may also induce non-oral papillomas in
the dog and confirm the opinion that a progression of viral papillomas into
carcinomas in dogs may occur.
PMID- 9646446
TI - In vivo functions of the auxiliary genes and regulatory elements of feline
immunodeficiency virus.
AB - Feline immunodeficiency virus (FIV) is a widespread lentivirus of domestic cats
that causes an acquired immunodeficiency syndrome (AIDS)-like disease similar to
human AIDS caused by human immunodeficiency virus. FIV has a complex genome
structure including structural, enzymatic and auxiliary genes and regulatory
elements. In this article, we review the in vivo roles of some of these FIV
auxiliary genes and regulatory elements, especially focusing on the dUTPase, vif,
and ORF-A genes and AP-1 binding site in the enhancer region of the long terminal
repeat, by comparison with those of other non-primate lentiviruses. These genes
and elements are considered to be important for viral replication, immunological
response and pathogenesis in cats.
PMID- 9646445
TI - Entry of African swine fever virus into Vero cells and uncoating.
AB - African swine fever virus (ASFV) enters Vero cells by adsorptive endocytosis
[Valdeira, M.L., Geraldes, A., 1985. Morphological study on the entry of African
swine fever virus into cells, Biol Cell. 55, 35-40]. Electron microscopy of a
lysosomotropic drug-controlled penetration indicated that this step takes place
in the endosomes, after fusion between the viral envelope and the limiting
membrane of the endosome. Inhibition studies with colcemid, cytochalasin B,
sodium azide, dinitrophenol, lysosomotropic weak bases, and the ionophore
monensin, showed that the virus uptake is largely independent of cytoskeletal and
lysosomal function, but dependent on oxidative phosphorylation. Some protease
inhibitors inhibited viral replication at an early step, indicating that the
initiation of infection depends on a viral proteolytic cleavage.
PMID- 9646447
TI - Development and evaluation of a novel antigen capture assay for the detection of
classical swine fever virus antigens.
AB - An antigen-capture enzyme immunoassay (EIA) was developed to detect classical
swine fever virus (CSFV) antigen directly from 10% w/v tissue suspension. The
assay, based on the sandwich principle, uses a biotinylated monoclonal antibody
bound to streptavidin-coated microplates as the capture system and a swine anti
CSFV antibody and rabbit anti-swine HRPO-conjugate as the detector system. The
antigen-capture EIA was compared with conventional virus isolation and polymerase
chain reaction (PCR) for detection of CSFV in tissues. The ability of the antigen
capture EIA to discriminate classical swine fever (CSF) from bovine viral
diarrhea and African swine fever viruses was also tested. The assay was shown to
detect 21 different strains of CSFV and was unreactive with tissues from
uninfected animals. Signal to noise (S/N) ratios were calculated from the EIA
absorbance values. Readings from samples positive by virus isolation (n = 47)
averaged a S/N ratio of 5.34. In contrast, samples negative by virus isolation (n
= 96) demonstrated a mean S/N ratio of 0.16. At S/N cut-off value of 1.0, all
samples that yield virus isolation and PCR negative result were negative in the
antigen-capture EIA. Compared with virus propagation in tissue culture using PK15
cells (followed by indirect peroxidase assay detection) and PCR, the EIA had a
specificity of 98.7% and a sensitivity of 91.4%. The EIA is simple, can be
performed in 4 h and lends itself to automation for screening of tissues sample
from pigs suspected of CSFV infection.
PMID- 9646448
TI - Blocking ELISA's for the distinction between antibodies against European and
American strains of porcine reproductive and respiratory syndrome virus.
AB - A double blocking ELISA was developed in order to satisfy the need for large
scale serological screening for PRRS and simultaneous distinction between
infection with European and American strains of PRRSV in pig herds. The
Immunoperoxidase monolayer assay (IPMA) and the double blocking ELISA enabled
distinction on serological basis between infection with European and American
strains of PRRSV. The distinction was possible from about day 7 after infection
of pigs with PRRSV. The double blocking ELISA enabled the distinction at later
stages of infection compared to the IPMA, irrespective of the strain involved.
PMID- 9646449
TI - A competitive ELISA for the specific diagnosis of contagious bovine
pleuropneumonia (CBPP).
AB - A competitive ELISA, using a specific monoclonal antibody, was designed to detect
antibodies to Mycoplasma mycoides subsp. mycoides SC, the agent of contagious
bovine pleuropneumonia. One monoclonal antibody was found suitable for such a
test, '117/5', it does not cross-react with any of the other mycoplasma species
tested, furthermore, its binding is inhibited by positive sera. The cutoff, 50%
of inhibition, was determined using a set of negative sera from CBPP-free areas.
The sensitivity was controlled with sera from artificially infected animals as
well as from sera from areas where CBPP is enzootic. In both cases, cELISA
compared favorably with CFT. The precocity of detection was similar but cELISA
detected more positives and the positive titers seemed to persist longer than in
the case of CFT. Lysis of the antigen used to coat the ELISA plates reduced the
variability of fixation and improved the repeatability of the test. A field
evaluation is now in progress which will determine the true sensitivity and
specificity of the test and also check if antibodies are detected after
vaccination.
PMID- 9646450
TI - Humoral immune responses to Mycoplasma hyopneumoniae in sows and offspring
following an outbreak of mycoplasmosis.
AB - Previously healthy sows, seropositive to Mycoplasma hyopneumoniae, developed
clinical signs of mycoplasmosis, as well as increasing amounts of antibodies to
M. hyopneumoniae during an outbreak of the disease in a herd. During the early
phase of the outbreak, young piglets (2 weeks) with maternal antibodies remained
healthy while older seronegative piglets (4-7 weeks) developed the disease. The
duration of the maternal antibodies to M. hyopneumoniae varied between litters
and was related to the amount of antibodies in the serum of the dam. In sows, the
level of serum antibodies decreased continuously from 4 weeks ante partum to
partus, and the level of antibodies in the whey of colostrum was comparable to
that in serum 4 weeks ante partum. After loss of maternal antibodies to M.
hyopneumoniae, seropositive animals were not found among piglets younger than 9
weeks. Therefore peripheral blood mononuclear cells (PBMC) were collected from
various age categories of piglets in order to measure the ability to produce
antibodies to M. hyopneumoniae in vitro. PBMC obtained from piglets aged 1 and 3
weeks produced few antibodies to M. hyopneumoniae. Significantly higher levels of
antibodies to M. hyopneumoniae were produced by PBMC obtained from pigs aged 5-9
weeks. Thus, the ability of PBMC to produce antibodies to M. hyopneumoniae in
vitro seemed to be age-dependent.
PMID- 9646451
TI - Comparison of serological tests for detection of Mycoplasma gallisepticum
antibodies in eggs and chicks hatched from experimentally infected hens.
AB - Specific pathogen free hens and males were experimentally infected with
Mycoplasma gallisepticum. Eggs were then collected, and a part was incubated and
set for hatching. Mycoplasma cultures were performed on infected adults and
antibodies to MG were analysed by use of slide agglutination (SA) test and
commercial ELISA tests on adults and chicks sera and on yolks from non incubated
eggs. Both ELISA tests could detect antibodies in yolks from non incubated eggs
laid three weeks after infection. SA and the three ELISA tests revealed positive
sera in chicks hatched from eggs laid as soon as one week after infection.
PMID- 9646452
TI - Effect of Bacillus subtilis spore administration on activation of macrophages and
natural killer cells in mice.
AB - The effect of Bacillus subtilis (strain A102) spores on the activation of murine
macrophages and natural killer cells (NK) was examined. The macrophage activity
and NK activity were enhanced by oral administration of A102 spores, and slightly
enhanced by oral administration of culture supernatant. There was no difference
in the results of macrophage activity and NK activity using other live or dead
spores. The NK activity and macrophage activity were increased with increments of
concentration up to 0.1 g per mouse, and both activities were decreased at
concentration of more than 0.15 g per mouse. The NK activity was increased 1 and
2 days after oral administration of A102 spores, and the activity level 2 days
after administration was about 3-fold higher than the level prior to treatment.
Macrophage activity was also increased from 1 to 3 days after oral administration
of A102 spores, and the activity level 3 days after administration was about 3
fold higher than the level prior to treatment. The induction of interferons at 1
day after oral administration in mouse serum was 5-fold higher than that in
controls. These findings indicate that oral administration of A102 gave rise to
the induction of interferons, and it is likely that macrophages and NK cells were
activated by interferons.
PMID- 9646453
TI - An avian pathogenic Escherichia coli strain produces a hemolysin, the expression
of which is dependent on cyclic AMP receptor protein gene function.
AB - An avian pathogenic Escherichia coli strain M1000 showed a clear zone of
erythrocyte lysis on sheep blood agar plates. The hemolytic activity was not
detected in the culture supernatant nor was any DNA sequence homologous to the E.
coli alpha-hemolysin gene detected in the chromosome or plasmid DNA of the
strain, indicating that the observed hemolysis was different from alpha-type. To
identify the genetic determinant responsible for the hemolysis, we performed
random Tn5 insertional mutagenesis and obtained one mutant, named M5005, that
totally lacked the hemolytic activity. Cloning and nucleotide sequencing of the
region flanking the transposon insertion site in the M5005 chromosome revealed
that the transposon was inserted within an open reading frame of the cyclic AMP
receptor protein (CRP) gene, which is involved in one of the global regulatory
networks of gene expression in E. coli. Nucleotide sequence analysis of the
intact crp gene of the strain M1000 showed that the CRP protein of M1000 is 99%
identical to that of K-12. Introduction of the intact crp gene on a low copy
plasmid into the mutant M5005 restored the hemolytic phenotype, confirming that
the mutation site in M5005 was in the crp gene. CRP plays a central role in
catabolite repression, the phenomenon by which the synthesis of many enzymes
required to metabolize various sugars is repressed in the presence of glucose.
When the hemolytic activity of E. coli M1000 grown in the presence of glucose was
examined, the hemolysis was totally impaired. These results indicate that the
avian pathogenic E. coli strain M1000 produces a hemolysin the expression of
which is dependent on crp gene function.
PMID- 9646454
TI - Isolation and molecular analysis of colonising and non-colonising strains of
Campylobacter jejuni and Campylobacter coli following experimental infection of
young chickens.
AB - Fourteen-day-old chickens were inoculated with selected Campylobacter coli and C.
jejuni strains. C. jejuni strains were of two subgroups based on a polymorphism
detected using a DNA probe and represented the profiles typical for the majority
of strains of either chicken or human origin. All C. coli strains previously
isolated from humans colonised chickens, whereas from 4/7 C. jejuni strains of
human origin, failed to colonise. Of 12 Campylobacter strains of chicken origin,
10 established a persistent colonisation in the chickens, and 2 strains colonised
poorly or not at all. Four strains that failed to colonise chickens were each
inoculated into groups of five birds. Three strains again did not colonise any of
the chickens and the fourth strain colonised four out of the five chickens, but
was poorly excreted. When infected chickens were placed in the same enclosure to
facilitate interchange of strains, C. jejuni strain 331 was found to be dominant
and colonised all 12 chickens by 21 days, displacing all other strains. C. jejuni
strain 331, was then inoculated into groups of five birds with previously
established colonisation by C. jejuni and C. coli strains. Strain 331 was able to
replace the C. jejuni strain in all five birds but established co-colonisation
with C. coli strain. Naturally occurring co-colonisation by two C. jejuni strains
was detected in one chicken out of 200 tested. There was no obvious correlation
between the type of DNA polymorphism in strains of chicken origin and their
ability to colonise chickens.
PMID- 9646455
TI - Molecular epidemiology of Mycobacterium bovis isolates from South America.
AB - One hundred seventy-eight isolates of Mycobacterium bovis were subjected to DNA
restriction fragment length polymorphism (RFLP) analysis, using the direct repeat
element (DR) and the polymorphic GC-rich repeat sequence (PGRS) as probes. By
combining the patterns generated by the two repeat DNA elements, 93 different
patterns were observed. One hundred-one isolates were grouped in clusters, which
include 25 different clusters. One pattern was the most frequently observed,
clustering 18.5% of isolates. It was only found in the Center and northeast
regions of Argentina and in one isolate from Paraguay. The isolates from Brazil
analyzed here presented exclusive patterns (only found in a particular region).
The number of exclusive patterns was high in all argentine regions: northeast
78%, center 81%, and Buenos Aires 81%.
PMID- 9646456
TI - Serological and bacteriological observations on experimental infection with
Salmonella hadar in chickens.
AB - Over the past 3 years the frequency of Salmonella hadar infections has increased
in Belgium in both poultry and humans. Therefore, the course of infection with S.
hadar in poultry was investigated. One day-old and 4 week-old specific pathogen
free chickens were orally infected with one of two S. hadar strains, SH1 or SH2.
Mortality was 6% (SH1) and 17% (SH2) in birds infected at 1 day-old. Chickens
infected at 1 day-old with SH2 showed a mild diarrhoea. The S. hadar faecal
excretion in birds infected at 1 day-old remained high throughout the experiment
until 12 weeks post-inoculation (pi). Faecal excretion was lower in older birds.
Antibodies to S. hadar were observed from 2 weeks pi (SH2, infected at 1 day-old)
or 4 weeks pi (SH1, both groups; SH2, chickens infected at 4 weeks of age). The
percentage of chickens with antibodies was higher after infection at 1 day-old
than after infection at 4 weeks of age. In a second experiment 1 day-old chicks
were infected with SH1 and autopsied at regular intervals until 42 days pi. SH1
was isolated from the caeca from 3 h pi onwards and from the liver and spleen
from 18 h until 14 days pi. Serous typhlitis and omphalitis were the main
lesions. The number of macrophages in the lamina propria of the caecal tonsils
was slightly increased from 18 h until 2 weeks pi. In the liver, inflammation was
observed in the portal triads and in the sinusoids. This study indicates that
infections with S. hadar lead to intense colonisation of the gut and extensive
faecal shedding. It may also cause invasive infections in 1 day-old chickens.
PMID- 9646457
TI - Nucleotide sequence homology to bovine viral diarrhea virus 2 (BVDV 2) in the 5'
untranslated region of BVDVs from cattle with mucosal disease or persistent
infection in Japan.
AB - Cytopathogenic and non-cytopathogenic bovine viral diarrhea viruses (BVDVs) were
isolated from cattle with mucosal disease or persistent infection in Japan. These
isolates were compared for antigenic properties by cross-neutralization tests
with Japanese reference strains of BVDV belonging to classical type 1.
Significantly low cross-reactivity to reference strains was noted, indicating the
viruses to possibly represent a new serotype in Japan. Thus, to determine the
genotype of the isolates, nucleotide sequences of the 5' untranslated region were
determined and compared with those of previously reported BVDV 1 and 2. The
isolates were clearly shown to belong to BVDV 2, not to BVDV 1.
PMID- 9646458
TI - Detection of acid production from carbohydrates by Riemerella anatipestifer and
related organisms using the buffered single substrate test.
AB - One hundred and twenty-one Riemerella anatipestifer field strains from wild
birds, domesticated poultry and pigs were examined for their ability to produce
acid from carbohydrates by using conventional biochemical and buffered single
substrate (BSS) test methods. The type strains of the species R. anatipestifer
and taxometrically related genera Chryseobacterium and Bergeyella were included
in the study. In contrast to 10 indole-positive R. anatipestifer variant strains,
only a few of the 111 typical indole-negative R. anatipestifer strains produced
acid from dextrin (32%), glucose (17%), maltose (14%) and trehalose (5%) when the
conventional test procedure was used. Using the BSS test all the field isolates
and the type strain of R. anatipestifer produced acid from one or more
carbohydrates, most of them from dextrin (96%), maltose (91%), glucose (87%),
mannose (83%), less frequently from fructose (38%) and only in some cases from
trehalose (19%). One hundred and six (87%) of the R. anatipestifer strains could
be assigned to 8 biovars, based on the diversity of the carbohydrate
acidification patterns. The remaining 16 R. anatipestifer isolates gave delayed
reactions and displayed 13 different carbohydrate acidification profiles. The
Chryseobacterium and Bergeyella type strains also produced acid from more
carbohydrates when the BSS test was used. The BSS-carbohydrate acidification
pattern of the Chryseobacterium indologenes strain was similar to that of R.
anatipestifer biovar 3.
PMID- 9646459
TI - The frequent detection of a treponeme in bovine digital dermatitis by
immunocytochemistry and polymerase chain reaction.
AB - A study was carried out to determine whether spirochaetes are frequently
associated with digital dermatitis in United Kingdom (UK) dairy cattle.
Histopathological examination of lesions using a silver stain showed a large
number of unidentified spirochaete-like organisms present in digital dermatitis
hoof skin tissue in all examined biopsies. Immunocytochemical staining
demonstrated that spirochaetes in skin lesions were identified by polyclonal
antisera to Borrelia burgdorferi, Treponema denticola and Treponema vincentii
(again all biopsies were positively stained), whereas monoclonal antibodies to B.
burgdorferi and any Treponema pallidum did not stain any organisms in all
biopsies. A PCR of 16S rRNA, previously shown to be specific for a new treponeme,
was employed and produced positive results from 82.4% of digital dermatitis
tissues. It is concluded that this spirochaete (or related spirochaetes), which
is similar to human oral treponemes, is frequently associated with, and may be
responsible for, pathological changes in digital dermatitis.
PMID- 9646460
TI - Presence of papillomavirus-like DNA sequences in cutaneous fibropapillomas of the
goat udder.
AB - Papillomatous lesions were isolated from the mammary skin of goats and examined
for evidence of papillomavirus (PV) infection by various criteria, including
gross morphology, histology and DNA hybridization. Although some lesions showed
gross papillomatous morphological and histological features similar to those
caused by papillomavirus in other species, no viral particles were detected.
Reverse slot hybridization revealed cross-hybridization between DNA extracted
from goat mammary papillomas and human papillomaviruses (HPV). Southern blot,
using ovine papillomavirus (OPV) and bovine papillomavirus type 5 (BPV 5) DNA
probes under conditions of reduced stringency (Tm -40 degrees C), detected
homologous sequences in 40% of the biopsies. DNA fragments corresponding probably
to a monomeric form (7000-8000 bp) of an unknown papillomavirus genome were
detected. This study provides evidence for the existence of papillomavirus-like
sequences in caprine mammary papillomas and suggests that a papillomavirus is
likely to be involved in the development of precancerous lesions of goat mammary
skin.
PMID- 9646461
TI - Promoter activity of sequence located upstream of the pseudorabies virus early
protein 0 gene.
AB - Promoter activity of the 5'-flanking region of the pseudorabies virus (PRV) early
protein 0 (EP0) gene was analysed by transient transfection assays employing
chloramphenicol acetyl transferase (CAT) reporter constructs. We identified a 213
bp segment of the viral genome that was capable of efficiently driving expression
of the EPO gene and a linked reporter gene upon transient transfection into Vero
cells. This segment lacked the typical TATA element, and possessed an initiator
element and the putative binding sites for the transcription factor Sp1 and
immediate-early protein IE180, a strong transactivator of PRV. By analysing 5'
deletion mutants of the segment, a 48 bp segment (from nucleotide positions -65
to -17), which possessed three Sp1 binding sites, was identified to be critical
for the promoter activity. Cotransfection of Vero cells with the mutant
constructs and an IE180 expression plasmid resulted in transactivation of only
those constructs in which the Sp1 sites were present. These results indicate that
the EP0 gene may be transcribed from the TATA-less promoter that responds to Sp1.
PMID- 9646462
TI - Experimental inoculation of swine at various stages of gestation with a Danish
isolate of porcine reproductive and respiratory syndrome virus (PRRSV).
AB - Following intranasal inoculation of three groups of pregnant swine (in total 11
dams) with a Danish isolate of porcine reproductive and respiratory syndrome
virus (PRRSV) on or about day 85, 70 and 45 of gestation, respectively,
reproductive disturbances were observed in the first two groups. Transplacental
transmission of PRRSV occurred in four out of five litters from dams inoculated
around day 85 of gestation and in two out of three litters from dams inoculated
on day 72 of gestation. In the third group, inoculated around day 45 of
gestation, transplacental infection could not be demonstrated. Thirty-two (56%)
piglets from dams inoculated on day 85 of gestation and 14 (33%) piglets from
dams inoculated on day 72 of gestation, were transplacentally infected. Sixteen
(28%) and six (14%) piglets, respectively, in these groups became infected in the
perinatal period. Thirty-two (56%) piglets from dams inoculated on day 85 of
gestation were stillborn or died within a 6-8 weeks observation period, 29 being
stillborn or dying within the first two weeks of observation. Thirteen (30%)
piglets from dams inoculated on day 72 of gestation died within the two weeks
observation period. The duration of the viraemic phase varied considerably, from
one day to four weeks, for both dams and their offspring. Most frequently, PRRSV
was isolated from lung and/or tonsil tissues from dead and euthanized piglets
younger than 14 days of age. Histopathological investigations of piglets
typically revealed focal nonsuppurative inflammatory conditions, especially in
the lung and heart. In conclusion, the present results support the hypothesis,
that PRRSV infection of dams late in pregnancy has the greatest likelihood of
transplacental infection of fetuses.
PMID- 9646463
TI - Antimicrobial susceptibility testing of Mycoplasma hyosynoviae isolated from pigs
during 1968 to 1971 and during 1995 and 1996.
AB - This study was conducted to compare the Minimal Inhibitory Concentrations (MICs)
for enrofloxacin, lincomycin, tetracycline, tiamulin and tylosin, of Mycoplasma
hyosynoviae, isolated from pigs at notably different intervals (1968-71 and 1995
96). Each group comprised 21 low passage isolates and a Danish reference strain
(M60) and the type strain (S16). MICs were determined in liquid medium with both
initial and final readings. Enrofloxacin, lincomycin, tetracycline and tiamulin
were active against all isolates, and tiamulin showed the highest activity. For
tylosin all the isolates from 1968-71 were highly susceptible, whereas the
isolates from 1995-96 could be divided into a highly susceptible (nine isolates)
and relatively resistant (12 isolates) group. This difference between old and new
strains was statistically significant (p = 0.0000415). The remaining agents,
enrofloxacin, lincomycin, tiamulin and tetracycline, showed an unaltered good
activity against M. hyosynoviae. The resistance to tylosin seems now to occur so
often that this antibiotic cannot be recommended for therapeutic use any more.
The most probable explanation for the emergence of resistance is the intensive
use of tylosin during many years for therapy and growth promotion.
PMID- 9646464
TI - Utility of an internal control for evaluation of a Mycoplasma meleagridis PCR
test.
AB - Mycoplasma meleagridis, a turkey pathogen, can be detected by PCR directly from
tracheal or genital swabs. However, up to 40% samples may contain inhibitory
substances. A DNA fragment, that can be amplified with M. meleagridis primers and
in the same cycling conditions, was constructed to use as an internal control
(IC) to check for these inhibitors. This IC can easily be distinguished from the
M. meleagridis amplicon after agarose gel electrophoresis since it is longer. Use
of this IC in PCR amplifications revealed that more than 35% of turkey tracheal
swabs and more than 45% of turkey cloacal swabs contained inhibitors. In most
cases, dilution (1:100) of swab lysates allowed amplification of the internal
control but DNA purification may be necessary to eliminate inhibitors (20% of
tracheal swabs and 5% of cloacal swabs). Use of this internal control DNA allowed
assessment of the efficiency of each individual reaction and ensured that the
reaction was not inhibited by interfering substances.
PMID- 9646465
TI - Binding characteristics of purified Escherichia coli K88ab fimbriae to guinea pig
erythrocyte membrane.
AB - The characteristics of the binding of biotinylated E. coli K88ab fimbriae to
guinea pig erythrocyte membranes, as a possible model of the target host cell
were studied. Binding showed sigmoidal dependence, with an apparent saturation at
about 0.8 ng of fimbriae. Hill coefficient values (h) were about 2-2.4, which
indicated that the receptor population showed positive cooperativity with at
least three binding sites. Apparent binding constants to the first and third
binding sites (1K3 and 3K3) were determined. Three K88ab binding proteins, of 67,
63 and 48 kDa, were identified on solubilized erythrocyte membranes and were
recovered mainly in a detergent phase, suggesting a possible integral
localization of the receptors.
PMID- 9646466
TI - Detection of virulent Rhodococcus equi in tracheal aspirate samples by polymerase
chain reaction for rapid diagnosis of R. equi pneumonia in foals.
AB - Polymerase chain reaction (PCR)-based assays were developed to detect virulent
Rhodococcus equi in transtracheal aspirate samples from sick foals showing
respiratory signs. An oligonucleotide primer pair from the sequence of the
virulence-associated 15- to 17-kDa antigen gene of the virulence plasmid in
virulent R. equi was used to amplify a 564 bp region by PCR, and the result was
confirmed by Southern blot hybridization. No positive reaction was seen in DNA
from 13 different microorganisms typically found in the respiratory tract. In
tracheal aspirates seeded with virulent R. equi, a visible band could detect 10
to 10(2) bacteria per PCR assay (10(3) to 10(4)/ml of the aspirate). Virulent R.
equi was demonstrated in 31 of 42 transtracheal aspirates by culture and colony
blot analysis, whereas a positive PCR result was observed in only 12 of the 31
culture positive samples. To prevent false-negative results, two methods were
developed: a nested PCR and a PCR in combination with enrichment cultures of
aspirates in the selective medium to increase the number of bacteria to 10(4)/ml
or more. All of the PCR-negative and culture-positive samples were positive by
the two methods. These results indicated that PCR-based assays provide a specific
and sensitive means to detect virulent R. equi in tracheal aspirates of foals,
and they are more rapid than the routine culture procedures for the diagnosis of
R. equi pneumonia in foals.
PMID- 9646467
TI - Rapid diagnosis and strain differentiation of Mycobacterium bovis in radiometric
culture by spoligotyping.
AB - An assessment of spoligotyping for rapid detection and strain typing of
Mycobacterium bovis isolates in radiometric culture was made. Spoligotyping was
applied to BACTEC 12B broth cultures of 54 lesioned bovine lymph node specimens
from 44 herds in Northern Ireland. A nucleic acid sequence capture technique was
performed on BACTEC cultures at growth index points of approximately
(approximately) 60, approximately 200, and 999. Definitive spoligotype patterns
were obtained for 90.4% and 94.2% of all 52 BACTEC culture-positives at growth
indexes approximately 60 and approximately 200, respectively. Within 10 days,
definitive spoligotype patterns were obtained for 84.6% of the culture-positives.
This technique, therefore, allowed earlier and more accurate diagnosis of M.
bovis than traditional methodologies, as well as simultaneous strain
differentiation. Application of this molecular tool to BACTEC cultures would be a
significant advance in bovine tuberculosis eradication programmes. Seven distinct
spoligotype patterns were identified in this study, 2 of which (ST21 and ST25),
had not been identified previously in cattle from Northern Ireland. Two
spoligotype patterns (ST1 and ST2) accounted for 80.7% of the culture-positives.
These were found to have widespread geographic distribution, whereas 1
spoligotype pattern (ST14) had limited geographical distribution.
PMID- 9646468
TI - Bovine platelet adhesion is enhanced by leukotoxin and sialoglycoprotease
isolated from Pasteurella haemolytica A1 cultures.
AB - Platelet and fibrin deposits are among characteristic changes observed in lung
alveoli of cattle with pasteurellosis induced by Pasteurella haemolytica (biotype
A, serotype 1). To determine whether the platelet function could be directly
affected by protein products produced by the bacterium, the effects of leukotoxin
and O-sialoglycoprotease, culture supernatant antigen secreted by Pasteurella
haemolytica A1, on bovine platelet activation were examined by evaluating the
enhancement of platelet adhesion to a negatively charged surface relative to
untreated control samples. The glycoprotease, or the leukotoxin, was added to
plasma free suspensions of bovine platelets and platelet adhesion assessed by two
parameters: (i) the number of 3H-adenine-labeled adherent platelets and (ii) the
morphology of unlabeled platelets adhering to the charged surface under scanning
electron microscopy (SEM). In the presence of calcium, the glycoprotease produced
a dose-dependent increase in adhesion. At a concentration of 4.0 micrograms
glycoprotease extract protein per 10(7) platelets, a 2-fold increase in adhesion
was observed which was similar to the increase in adhesion induced by 0.10 units
of thrombin, a known platelet agonist. Both increased platelet adhesion and
platelet aggregation were observed with 0.8 microgram glycoprotease extract
protein in the presence of calcium. The response of the bovine platelet
suspensions to leukotoxin extract protein was dependent on the dosage of the
leukotoxin. Adhesion was enhanced at dosages of 25 micrograms leukotoxin protein
per 10(7) platelets and below, while at dosages of 50 micrograms and above
adhesion was suppressed. Thus, the two proteins secreted by P. haemolytica may
interact directly with bovine platelets to initiate platelet aggregation and
fibrin formation in alveolar tissue in pneumonic pasteurellosis.
PMID- 9646469
TI - Potential virulence factors of Streptococcus dysgalactiae associated with bovine
mastitis.
AB - Mastitis caused by environmental pathogens is a major problem that affects many
well-managed dairy herds. Among the environmental pathogens, Streptococcus
dysgalactiae is isolated frequently from intramammary infections during lactation
and during the nonlactating period. In spite of its high prevalence, little is
known about factors that contribute to the virulence of S. dysgalactiae. During
the last decade, several cell-associated and extracellular factors of S.
dysgalactiae have been identified; yet, the relative importance of these factors
in the transmission and pathogenesis of mastitis caused by S. dysgalactiae has
not been defined. Streptococcus dysgalactiae can interact with several plasma and
extracellular host-derived proteins such as immunoglobulin G, albumin,
fibronectin, fibrinogen, collagen, vitronectin, plasminogen, and alpha 2
macroglobulin. These interactions are mediated by bacterial surface proteins.
This organism also produces hyaluronidase and fibrinolysin which may be involved
in promoting dissemination of the organism into host tissue. Streptococcus
dysgalactiae adheres to and is internalized by bovine mammary epithelial cells in
vitro. Involvement of host cell kinases, intact microfilaments and de novo
eukaryotic protein synthesis are required for internalization of S. dysgalactiae
into bovine mammary epithelial cells; a process that appeared to occur by a
receptor-mediated endocytosis mechanism. However, de novo bacterial protein
synthesis was not required for epithelial cell internalization. Furthermore, S.
dysgalactiae survived within mammary epithelial cells for extended periods of
time without losing viability or damaging the eukaryotic cell. Further research
on characterization of host-pathogen interactions that take place during the
early stages of mammary gland infection will enhance our understanding of
pathogenesis of intramammary infection which may contribute to development of
methods to minimize production losses due to mastitis.
PMID- 9646471
TI - The interaction of Streptococcus dysgalactiae with plasmin and plasminogen.
AB - The activation of plasminogen and the binding of plasmin by bacteria may have
many effects which promote infection. The occurrence of such activities in
streptococci is well documented; however, these are yet to be demonstrated for S.
dysgalactiae. Consequently, the ability of this bacterium to activate mammalian
plasminogen and bind either plasmin or its zymogen was investigated. Activation
of bovine plasminogen was dependent on both the strain and the growth medium used
for cultivation. Eighteen strain were able to activate bovine and ovine
plasminogen and some of these also activated plasminogen from the horse, rabbit
and pig. None activated human plasminogen and one strain (CE127) did not activate
plasminogen from any source. Tricine-SDS PAGE and zymographic analysis of culture
supernatants showed that bovine plasminogen was activated by four out of six
strains at two locations corresponding to 16 kDa and 10 kDa. Following the growth
of five strains in the presence of bovine plasminogen, all but strain CE127 bound
high levels of plasmin activity. In contrast, following growth in human
plasminogen none of the strains exhibited bound plasmin activity although all
could bind human plasmin directly. All strains were also able to bind bovine and
human plasminogen in such a way as to allow its activation by urokinase. We
conclude that S. dysgalactiae is capable of activating mammalian plasminogen in a
species-specific fashion and that the bacterium is also capable of binding
plasmin and plasminogen with an apparent preference for bovine plasmin over human
plasmin and/or plasminogen from either species.
PMID- 9646470
TI - Spacer oligotyping of Mycobacterium bovis isolates compared to typing by
restriction fragment length polymorphism using PGRS, DR and IS6110 probes.
AB - Ninety-two Mycobacterium bovis isolates from cattle, deer and badgers in Northern
Ireland and the Republic of Ireland were genotyped by spacer-oligotyping
(spoligotyping) and 67 of these were analysed by restriction fragment length
polymorphism (RFLP). RFLP analysis was performed using three DNA probes, PGRS, DR
and IS6110. Forty-seven of the M. bovis isolates were from 45 different sources;
these were typed using both RFLP and spoligotyping. These 47 isolates could be
differentiated into 24 different RFLP types and 15 distinct spoligotypes.
Although RFLP was found to be more discriminatory compared to the present
spoligotyping technique, spoligotyping was able to differentiate 21 RFLP type
'ACA' isolates into three different patterns. The remaining 45 M. bovis isolates
were from a small case study, involving infected cattle, deer and badgers from
the same geographic region. All these isolates were analysed by spoligotyping and
a selection of 20 isolates were RFLP typed. All the isolates in the case study
had the same spoligotype pattern with the exception of one cervine isolate.
Similarly all the isolates typed by RFLP had the same pattern. Consequently, the
predominant strain in the case study was not host restricted. The consistency
between the results obtained using the two techniques indicates the potential
value of both techniques for epidemiological studies. Spoligotyping was found to
be a much more rapid technique and easier to perform, requiring less
sophisticated computer software for strain typing. Spoligotyping results were
more readily documented and analysed and the technique was also more suitable
than RFLP analysis for large-scale screening studies.
PMID- 9646472
TI - Prevalence of verotoxin-producing Escherichia coli harbored in the intestine of
cattle in Japan.
AB - The production of verotoxin was examined in 2152 Escherichia coli isolates from
387 cattle in Japan from 1992 to 1994. The toxin was detected in 263 isolates
from 94 cattle (detection rate: 24.3%). Verotoxin-producing E. coli (VTEC) was
isolated from the cattle in 15 out of 17 prefectures, and the strains were
divided into 33 serotypes. E. coli O157:H7 was isolated from 7 out of 387 cattle
(detection rate: 1.8%) in four prefectures. These results suggest that VTEC is
widely distributed in Japan and include a wide variety of serotypes.
PMID- 9646473
TI - Tularemia in a common marmoset (Callithrix jacchus) diagnosed by 16S rRNA
sequencing.
AB - We report a case of tularemia in a common marmoset (Callithrix jacchus) diagnosed
by determination of the isolate's 16S ribosomal RNA (rRNA) gene sequence.
Pathological examination of the animal revealed a multifocal acute necrotizing
hepatitis, interstitial nephritis, splenitis, and lymphangitis of the mandibular,
retropharyngeal, and cervical and mesenteric lymph nodes. Moreover, multiple foci
of acute necrosis were found in the epithelium of the jejunum and the
interstitium of the lung. Bacteriological investigations revealed a septicemia.
The isolated infectious agent was uncommon, not routinely diagnosed in our
laboratory and therefore difficult to identify by conventional tools in a
reasonable time and effort. thus, we decided to perform a genetic analysis based
on the 16S rRNA gene sequence. Thereby, an infection with Francisella tularensis,
the causative agent of tularemia, was unambiguously diagnosed. This shows the
great advantage 16S rRNA gene sequencing has as a general identification approach
for unusual or rare isolates.
PMID- 9646474
TI - Replication of bovine respiratory syncytial virus in bovine and ovine peripheral
blood lymphocytes and monocytes and monocytic cell lines.
AB - The present study compared the replication of bovine respiratory syncytial virus
(BRSV) in bovine and ovine peripheral blood mononuclear cells, ovine and bovine
monocytic cell lines and ovine alveolar macrophages. Low titres of virus were
detected in ovine and bovine lymphocytes and monocytes 24-96 h post-exposure to
the virus but there was no apparent replication of the virus in ovine alveolar
macrophages during the culture period. The virus replicated to higher but
statistically insignificant titres in ovine and bovine peripheral blood monocytes
than in lymphocytes, with lymphocytes yielding peak titres significantly earlier.
The secondary cell lines obtained from ovine liver and bone marrow also supported
the replication of BRSV to high titres. The titres of BRSV in ovine and bovine
lymphocytes and monocytes were significantly lower than in secondary cell lines.
The addition of human recombinant tumour necrosis factor alpha after exposure to
the virus or pre-incubation of ovine or bovine monocytic cells with either human
recombinant interleukin 2 or phorbol myristate acetate before exposure to BRSV,
did not significantly affect virus titre. Pre-incubation of cells with
indomethacin or actinomycin significantly lowered virus titre (p < 0.05).
PMID- 9646475
TI - Evaluation of baculovirus-expressed bovine herpesvirus-1 (BHV-1) glycoproteins
for detection and analysis of BHV-1-specific antibody responses.
AB - Baculovirus (Autographa californica nuclear polyhedrosis)-expressed bovine
herpesvirus-1 (BHV-1) glycoproteins B (gB), gC, and gD were developed and
characterized. The recombinant proteins retained their antigenic properties as
determined by immunoblotting against monoclonal antibodies. The proteins were
examined as antigens for detection of BHV-1 infection and for the analysis of
antibody responses to the individual viral proteins. A total of 115 bovine serum
samples were tested for their reactivity with individual recombinant proteins
from baculovirus-infected Spodoptera frugiperda (SF-9) cell lysates by enzyme
linked immunosorbent assay (ELISA), western blotting, and dot blotting assays.
These serum samples were previously tested for BHV-1-specific antibodies by virus
neutralization (VN) at the veterinary diagnostic laboratory. All 90 serum samples
tested positive with VN were positive by ELISA against gC and gD, separately.
However, reactivities of sera against gB were generally low and inconsistent. On
the other hand, out of 25 sera that were negative with VN, 22 sera were
consistent and gave negative results against gC or gD by ELISA, whereas
reactivities with gB were inconsistent. Similar results were obtained when the
sera were tested by western blotting and dot blotting. The positive sera
consistently reacted strongly against gC and to a lesser extent gD. These results
suggest that baculovirus expressed gC from infected cell lysate can be used as a
potential diagnostic antigen for detection of anti-gC-specific antibody responses
in BHV-1 infected cattle.
PMID- 9646476
TI - Immune responses and protective efficacy of recombinant baculovirus-expressed
glycoproteins of equine herpesvirus 1 (EHV-1) gB, gC and gD alone or in
combinations in BALB/c mice.
AB - Baculovirus-expressed glycoproteins of EHV-1 gB, gC and gD alone or in
combination evoked antibody responses and protected vaccinated mice against a
challenge with EHV-1. gB, gD, gB + gC, gB + gD and gC + gD elicited very high
levels of ELISA antibodies while gC and gC + gD elicited high levels of virus
neutralising antibodies. Western blotting demonstrated that the antibodies
produced were not only specific for the baculovirus-expressed glycoproteins gB,
gC and gD, but also highly specific for each EHV-1 glycoprotein. Vaccination of
mice with gB or gD prevented clinical signs of infection in mice challenged with
EHV-1 and all vaccinated groups of mice except controls showed a rapid clearance
of virus from the lungs and a reduction in lesions characteristic of
herpesviruses in the lungs post-challenge. Notably, the lungs of mice vaccinated
with gB, gD or gB + gD and challenged with EHV-1 showed prominent peribronchiolar
and perivascular aggregations of mononuclear cells, predominantly lymphocytes.
Immunocytochemical staining of these sections showed large numbers of T cells,
suggesting an active role for these cells at the site of virus replication post
challenge.
PMID- 9646477
TI - Susceptibility of alpine ibex to conjunctivitis caused by inoculation of a sheep
strain of Mycoplasma conjunctivae.
AB - We evaluated the susceptibility of alpine ibex (Capra ibex ibex) to mycoplasmal
conjunctivitis induced by a strain of Mycoplasma conjunctivae isolated from
domestic sheep by inoculation of three alpine ibexes with 1.2 x 10(6) colony
forming units of M. conjunctivae in the conjunctival sac of both eyes. One more
ibex was exposed to the infection by contact. Experimental animals were free of
M. conjunctivae and ocular Chlamydia infection before inoculation. Conjunctivitis
and serous to mucous lachrymation became apparent in all four ibexes. Clinical
signs began within 2 days in inoculated animals and 22 days after the beginning
of the experiment in the contact ibex. M. conjunctivae was demonstrated up to the
63th day post-inoculation by cultural and PCR-methods. After 63 days,
histopathologic examination revealed nearly normal ocular tissues, and M.
conjunctivae could be detected from two eyes only. No other infectious agents
which might cause conjunctivitis or keratitis, including Chlamydia psittaci and
Branhamella ovis, were involved. Our investigation indicates that sheep-strains
of M. conjunctivae can induce conjunctivitis in alpine ibex, thus showing
pathogenicity of this organism for Caprinae species other than domestic sheep and
goats.
PMID- 9646478
TI - Biochemical and biological characterizations and ribotyping of Actinomyces
pyogenes and Actinomyces pyogenes-like organisms from liver abscesses in cattle.
AB - Actinomyces pyogenes is the second most frequently encountered pathogen, next
only to Fusobacterium necrophorum, in liver abscesses of feedlot cattle. Ninety
one isolates, presumptively identified as A. pyogenes, isolated from liver
abscesses of cattle were studied. Biochemical characteristics determined by the
API 20 Strep kit were similar to those reported previously for A. pyogenes
isolated from other infections, except that 18% of isolates hydrolyzed esculin.
Nine isolates that resembled A. pyogenes in morphology and in certain biochemical
characteristics, but fermented mannitol and/or raffinose, were called A. pyogenes
like (APL) organisms. The five antimicrobial agents, bacitracin,
chlortetracycline, oxytetracycline, tylosin, and virginiamycin were inhibitory to
all strains of A. pyogenes and APLs. Generally, APL organisms had higher mean
hemolytic and leukotoxic activities than A. pyogenes. All isolates of A. pyogenes
and APLs produced proteases and neuraminidases. Ribotyping with endonucleases,
including BstEII, ClaI, EcoRI, EcoRV, HaeIII, MboI, PvuII, SalI, and SmaI alone
or in combinations, showed considerable genetic heterogeneity in both A. pyogenes
and APLs. No specific ribopattern characteristic of each group was observed with
any of the endonuclease used. The origin of A. pyogenes and APLs and the relative
importance of APLs in causing liver abscesses in feedlot cattle are not known.
PMID- 9646479
TI - Antimicrobial susceptibility of Moraxella bovis.
AB - The antimicrobial susceptibility of 55 isolates of Moraxella bovis to seven
antibiotics was evaluated by broth microdilution procedures. The isolates had an
MIC90 of < or = 1 mg/l to erythromycin, ceftiofur, and ampicillin; 4 mg/l to
tilmicosin; 16 mg/l to tylosin and gentamicin; and had MIC90s of > or = 32 mg/l
for oxytetracycline. The modal MIC values for these antibiotics were as follows:
ampicillin, < 0.25 mg/l; ceftiofur, < or = 0.125 mg/l; tilmicosin, 2 mg/l;
tylosin, 8 mg/l; erythromycin 1 mg/l; oxytetracycline, < or = 0.5 mg/l; and
gentamicin, < or = 0.5 mg/l. This in vitro data showed most antibiotics have low
MICs that are suggestive of clinical efficacy.
PMID- 9646480
TI - Restriction fragment length polymorphism and spacer oligonucleotide typing: a
comparative analysis of fingerprinting strategies for Mycobacterium bovis.
AB - The combination of conventional investigation and DNA fingerprinting is yielding
important insights into the epidemiology of Mycobacterium bovis infections.
Various genetic markers used in restriction fragment length polymorphism (RFLP)
have recently been exploited for fingerprinting of M. bovis isolates. The newly
developed spacer oligonucleotide typing aimed to investigate the polymorphism of
M. tuberculosis in the DR locus, has also been applied to the molecular typing of
M. bovis isolates. This work compared the performance of the insertion sequence
(IS) IS6110, IS1081 and the genetic elements polymorphic G + C-rich repeat (PGRS)
and direct repeat (DR) used in RFLP analysis with spoligotyping using a group of
128 Spanish M. bovis isolates. In this study, the most sensitive technique for
identifying polymorphism in M. bovis was PGRS-RFLP, closely followed by IS6110
RFLP. We propose several schemes for fingerprinting of these isolates, however,
the clear geographical variations found by different authors makes the study of
each local situation indispensable. An international consensus in the methods
used would be desirable for efficient interlaboratory comparison of strains.
PMID- 9646481
TI - Fragrance compounds and amphiphilic association structures.
AB - Fragrance formulations have traditionally been based on alcohol as the solvent,
but the recent legal restrictions on volatile organic solvents have prompted the
industry to change to aqueous solubilized systems. The article reviews the
fundamental factors in the application of such systems evaluating the influence
by different amphiphilic association structures on the vapor pressure of
fragrance compounds. This information is subsequently used to estimate the
variation of fragrance compound vapor pressures during evaporation. The results
reveal that the vapor pressure versus time variation is improved compared to
solvent-based formulations.
PMID- 9646482
TI - Sintered octadecylsilica as monolithic column packing in capillary
electrochromatography and micro high-performance liquid chromatography.
AB - Fused-silica capillaries were packed with porous 6-microns octadecylated silica
microspheres and subjected to thermal treatment in order to obtain a column with
porous silica based monolithic packing. After sintering, the monolithic packing
was reoctadecylated in situ with dimethyloctadecylchlorosilane. The mechanical
strength and stability of the monolithic column were significantly greater than
those of conventional columns packed with particulate stationary phase. The
performance of the columns was evaluated in both mu-HPLC and capillary
electrochromatography (CEC) of small aromatic compounds and polycyclic aromatic
hydrocarbons with 10 mM borate, pH 8.0, in acetonitrile-water mixtures as the
mobile phase. Since no untoward bubble formation was observed, CEC could be
performed in a CZE unit without the need for pressurizing the monolithic column.
The plate efficiency of the monolithic column was similar to that of columns
freshly packed with the same particles and was always higher in the CEC than in
the mu-HPLC under otherwise identical conditions. The electrosmotic flow (EOF)
velocity increased with the acetonitrile content of the eluent in open fused
silica capillaries with octadecylated innerwall and in columns packed with
sintered octadecylsilica. In contradistinction, the EOF velocity decreased with
the organic strength of the eluent in raw fused-silica capillaries. The opposite
trend is attributed to the different effect of changing organic modifier
concentration on the accessibility of silanol groups at the raw and octadecylated
silica surfaces.
PMID- 9646483
TI - Optimal membrane choice for microdialysis sampling of oligosaccharides.
AB - An analytical methodology based on microdialysis sampling, high-performance anion
exchange chromatography and integrated pulsed electrochemical detection for the
monitoring of oligosaccharides in bioprocesses is presented. Amylopectin and
model maltooligosaccharide standards; glucose, maltose, maltotriose,
maltotetraose, maltopentaose, maltohexaose and maltoheptaose were used to
demonstrate its versatility in view to sampling in enzymatic bioprocesses. The
performance and characteristics of membranes with the same cut-off ranging
between 3 and 100 kDa, were evaluated with respect to their extraction fraction
(EF), permeability factors, temperature stability and protein (enzyme)
interaction. All investigated membranes showed some non-specific interaction with
enzymes. The EF and non-specific membrane-enzyme interactions were higher for the
polysulfone membranes compared with the polyamide and polyethersulfone membranes.
For all saccharides, the EF was independent of the concentration even for a 250
fold change in concentration. The EF and morphology of the membranes in their
dehydrated state, as observed using scanning electron microscopy did not show any
significant difference between membranes exposed to a 90 degrees C temperature
for 3 and 24 h indicating their applicability to the study of high temperature
bioprocesses.
PMID- 9646484
TI - Enrichment and purification of proteins of Haemophilus influenzae by
chromatofocusing.
AB - Haemophilus influenzae is a bacterium of pharmaceutical interest of which the
entire genome has been sequenced. Identification of low-abundance proteins in a
two-dimensional map is important for the detection of new drug targets. We
applied chromatography on Polybuffer Exchanger (chromatofocusing) in order to
fractionate and enrich H. influenzae proteins, possibly low-copy-number gene
products, from larger volumes. Two proteins, major ferric iron-binding protein
(HI0097) and 5'-nucleotidase (HI0206) were obtained in pure form and hypothetical
protein HI0052 was purified to near homogeneity by this single purification step.
Four other proteins, aspartate ammonia lyase (HI0534), peptidase D (HI0675),
elongation factor Ts (HI0914) and 5-methyltetrahydropteroyltriglutamate
methyltransferase (HI1702), were strongly enriched so that chromatography on
Polybuffer Exchanger can be used as an initial step for their isolation.
Approximately 125 proteins were identified in the fractions collected from the
column. Seventy of these were for the first time identified after chromatography
on Polybuffer Exchanger. The proteins enriched by the chromatofocusing step
include both low-abundance as well as high-copy-number gene products. They do not
belong to a single protein class and the majority of them are enzymes with
various functions. The results include a list and a two-dimensional map of the
proteins enriched by chromatofocusing. They may be useful in the search of drug
targets and in the design of purification protocols for the isolation of
homologous proteins from related microorganisms.
PMID- 9646485
TI - Determination of ascorbic acid in food by column liquid chromatography with
electrochemical detection using eluent for pre-run sample stabilization.
AB - Determination of ascorbic acid (AA) in food was performed by column liquid
chromatography with electrochemical detection using an eluent (100 mM KH2PO4 (pH
3) with 1 mM ethylenediaminetetraacetic acid disodium dihydrate) for pre-run
sample stabilization. The applied potential was set at 400 mV vs. an Ag/AgCl
reference electrode. The proposed method was simple, rapid (analysis time: ca. 8
min), sensitive (detection limit: ca. 0.5 ng per injection (20 microliters) at a
signal-to-noise ratio of 3), highly selective and reproducible [relative standard
deviation: ca. 1.8% (n = 5)]. The calibration graph for AA was linear in the
range 0.1-16 ng per injection (20 microliters). Recovery of AA was over 90% by
the standard addition method.
PMID- 9646486
TI - Derivatization in capillary electrophoresis.
AB - In recent years capillary electrophoresis (CE) has been developed into a
versatile separation technique, next to gas and liquid chromatography (LC), well
suited for the determination of a wide variety of e.g., pharmaceutical,
biomedical and environmental samples. The main advantages of CE over
chromatographic separation techniques are its simplicity and efficiency. It is
well recognized, however, that the sensitivity and selectivity of the detection
are relatively weak points of CE. One way to overcome these limitations is the
conversion (derivatization) of the analytes into product(s) with more favourable
detection characteristics. Although, in principle, almost any detection mode can
be combined with a derivatization procedure, in practice, fluorescence monitoring
is favoured in most cases. This paper aims to give a short overview on the
various reagents that can be used for pre-, post- and on-column derivatization in
CE. First, a short introduction is given on CE as an analytical technique,
followed by a discussion of the pros and cons of the various modes of
derivatization, a comparison of derivatizations in CE with derivatizations in LC,
the principles of fluorescence and prerequisites for a good fluorophore and the
potential of using diode lasers in combination with a labelling procedure. With
respect to the derivatization reagents the emphasis is on the labelling of amino,
aldehyde, keto, carboxyl, hydroxyl and sulfhydryl groups.
PMID- 9646487
TI - Therapeutic drug monitoring by capillary electrophoresis.
AB - Because of the ease of analysis and the high resolution, drug analysis is
becoming the best example for the application of capillary electrophoresis.
Therapeutic drug monitoring is a specialized area of drug analysis performed in
clinical laboratories for patient care. CE offers high resolution and speed with
the low operating costs needed in patient care. However, CE has a few
limitations, mainly poor detection limits and precision. Simple methods of
stacking, which enhance drug detection to overcome the poor sensitivity of CE are
stressed. Serum has a unique matrix with a high content of proteins and salts
which can have adverse effects on separation by CE. For successful analysis,
special maneuvers are employed to decrease these matrix effects. Studies that
have addressed the improvement of the precision of CE are summarized. CE offers
the possibility of bringing chiral separations into the routine arena.
PMID- 9646488
TI - Chiral analysis by capillary electrophoresis using antibiotics as chiral
selector.
AB - The separation of chiral compounds by capillary electrophoresis (CE) is a very
interesting field of research in different areas such as pharmaceutical,
environmental, agricultural analysis etc. The separation of two enantiomers can
be achieved in CE using a chiral environment interacting with the two analytes on
forming diastereoisomers with different stability constants and thus different
mobilities. A wide number of chiral selectors have been employed in CE and among
them glycopeptide antibiotics exhibited excellent enantioselective properties
towards a wide number of racemic compounds. Vancomycin, ristocetin A, rifamycins,
teicoplanin, kanamycin, streptomycin, fradiomycin, and two vancomycin analogues,
added to the background electrolyte (BGE), are the antibiotics studied by CE
running the separation in untreated and/or coated fused-silica capillary. Due to
adsorption and absorption phenomena, some drawbacks can be expected when using
bare fused-silica capillary, e.g., changes of electroosmotic flow (EOF), broaden
peaks, reduced efficiency and low sensitivity. Coated capillary and counter
current mode can be the solution to overcome the above mentioned problems. This
review surveys the separation of enantiomers by CE when macrocyclic antibiotics
are used as chiral selector. The enantioselectivity can be easily controlled
modifying several parameters such as antibiotic type and concentration, pH, ionic
strength and concentration of the background electrolyte, organic modifier etc.
The paper also presents a list of the latest chiral separations achieved by CE
where antibiotics were used as chiral selector.
PMID- 9646489
TI - Application of capillary zone electrophoresis-inductively coupled plasma mass
spectrometry and capillary isoelectric focusing-inductively coupled plasma mass
spectrometry for selenium speciation.
AB - The high resolution potential of capillary electrophoresis (CE) makes CE
techniques valuable for separations of selenium species, both, organic and
inorganic. Such effective separations of charged species are possible using the
CZE mode (Z = zone). Very powerful separations can be achieved by capillary
isoelectric focusing, when analysing molecules showing different isoelectric
points (pI) values, such as organic Se species. Inductively coupled plasma (ICP)
MS is an element-specific multi-element detector, providing extremely low
detection limits. The combination of CE with ICP-MS promises a powerful tool for
metal speciation. Therefore, an online hyphenation of CE [using capillary zone
electrophoresis (CZE) or capillary isoelectric focusing (cITP) model] with ICP
MS, which was developed earlier, was modified and applied to selenium speciation.
Separation was differentiated from the detection step during hyphenation. This
resulted in short separation times (10 min) and a subsequent detection step
lasting 100 s. Firstly, a CZE method was applied, providing a separation of six
Se species of interest in one run [Se(IV), Se(VI), selenium carrying glutathione
(GSSeSG), selenomethionine (SeM), selenocystine (SeC), selenocystamine (SeCM)].
This CZE method used an alkaline background electrolyte (Na2CO3/NaOH). The Se
species were separated sufficiently from each other. Detection limits were
calculated as 10 or 20 micrograms Se l-1 for inorganic Se species and 30-50
micrograms Se l-1 for organic Se species. The method was applied to standard
mixtures and body fluids like human milk and serum. Secondly, a cIEF separation
(pH range 2-10) was employed for organic Se species only in parallel. Detection
limits were around 10-30 micrograms Se l-1. The method was applied to standard
mixtures and body fluids like human milk and serum.
PMID- 9646490
TI - Thermal stability studies of immunoglobulins using capillary isoelectric focusing
and capillary zone electrophoretic methods.
AB - The affinity of an antibody towards its antigen is highly specific to its
conformation, in order to have optimal antibody-antigen interaction. The increase
of temperature might cause changes in antibody conformations. The change of
structure conformations may be reflected in the isoelectric points (pI values),
peak shape and absorbance of the antibody. In this study, a monoclonal antibody
was heated over a period of time. Capillary isoelectric focusing (cIEF) and
capillary zone electrophoresis (CZE) were used to monitor the change in the
antibody. The longer the heating period, the lower the pI values were under cIEF
conditions. CZE also showed changes in peak shapes and decreases in absorbance of
the antibody with heating.
PMID- 9646491
TI - Insulin stacking for capillary electrophoresis.
AB - Stacking methods are very important in overcoming the poor detection limits in
capillary electrophoresis. Human insulin, a polypeptide, was concentrated on the
capillary (stacked) based on three different and simple treatment methods to the
sample: dilute buffers, high salt content, and acetonitrile (66%) were added to
the sample to induce stacking. A dilute buffer in the sample caused a limited
stacking, while acetonitrile treatment and high salt content in the sample caused
much greater (approximately 20-fold) stacking. High salt concentration in the
sample caused stacking presumably by a transient isotachophoretic method. In
addition to stacking, the acetonitrile treatment removed the excess proteins in
the sample. Insulin did not denature or precipitate in 66% acetonitrile as
confirmed by high-performance liquid chromatography (HPLC) and immunoassays.
Acetonitrile treatment enabled one-third of the capillary to be loaded with
sample thus increasing the detection signal greatly. The insulin peak after
acetonitrile treatment and separation by capillary electrophoresis (CE) was
confirmed by HPLC and by CE fraction collection followed by immunoassay. Based on
acetonitrile treatment, insulin detection in pancreatic tissue homogenates is
shown to be feasible.
PMID- 9646492
TI - Capillary electrophoresis in biochemical and clinical laboratoriesp selected
attractive examples.
AB - As demonstrated by selected examples from our laboratories, CE is a unique
methodology for purity control of synthetic as well as natural tissue-isolated
biopolymers, a prerequisite before reliable biotestings should be performed. A
combination of rapid matrix-assisted laser desorption ionization mass and CE
electrophoretic mobility determinations facilitates primary sequence
determinations of enzymatic peptide digest mixtures often making costly Edman
degradations unnecessary. The enormous separation efficiency and large variety of
different possible separation modes in CE, allow detection of single components
in complex mixtures which is demonstrated by the apolipoprotein A-I determination
in human blood serum in this communication.
PMID- 9646493
TI - Trace chromatographic analysis of dimethyl sulfoxide and related methylated
sulfur compounds in natural waters.
AB - Dimethyl sulfoxide (DMSO) occurs in the environment as a result of a number of
biogenic and anthropogenic production and emission processes. It is an
environmentally significant compound because of its use as a substrate by
bacteria and its potential role in the biogeochemical cycle of dimethyl sulfide
(DMS), a climatically active trace gas. In this paper, current methods for DMSO
determination at nanomolar levels in natural waters, all involving gas
chromatography, are reviewed. Direct injection and separation of aqueous DMSO
offers a simple and fast application, but exhibits limited sensitivity due to
limitation on injection volumes. So far, most authors have preferred DMSO
reduction and subsequent analysis of the evolved DMS by purge-and-trap
preconcentration and flame photometric detection. Several reducing agents have
been used, though some require cumbersome procedures or are very sensitive to
operational conditions. The common algal component dimethylsulfoniopropionate
(DMSP) acts as an interference in some reduction methods and, therefore, either
DMSP elimination prior to DMSO analysis or correction a posteriori is required.
DMSO can be analyzed along with DMS, methanethiol, dimethyl disulfide and DMSP in
the same water sample, either sequentially or separately, so that comprehensive
speciation of methylated sulfur is obtained. Owing to the biological activity of
DMSO, appropriate water sampling and handling procedures must be applied.
Acidification and freezing appear to be suitable for aqueous DMSO storage,
although immediate analysis in the field is always preferable. Future directions
of DMSO determination in aquatic environments are suggested.
PMID- 9646494
TI - Characterization of large-pore polymeric supports for use in perfusion
biochromatography.
AB - Perfusion chromatography is uniquely characterized by the flow of a portion of
the column eluent directly through the resin in the packed bed. The benefits of
this phenomenon and some of the properties of perfusive resins have been
described before, and can be summarized as enhanced mass transport to interior
binding sites. Here we extend the understanding of this phenomenon by comparing
resins with different pore size distributions. Resins are chosen to give
approximately the same specific pore volumes (as shown in the characterization
section) but the varying contribution of large pores is used to control the
amount of liquid flowing through the beads. POROS R1 has the largest contribution
of throughpores, and therefore the greatest intraparticle flow. POROS R2 has a
lower contribution of throughpores, and a higher surface area coming from a
greater population of diffusive pores, but still shows significant mass transport
enhancements relative to a purely diffusive control. Oligo R3 is dominated by a
high population of diffusive pores, and is used comparatively as a non-perfusive
resin. Although the pore size distribution can be engineered to control mass
transport rates, the resulting surface area is not the only means by which
binding capacity can be controlled. Surface coatings are employed to increase
binding capacity without fundamentally altering the mass transport properties.
Models are used to describe the amount of flow transecting the beads, and
comparisons of coated resins to uncoated (polystyrene) resins leads to the
conclusion that these coatings do not obstruct the throughpore structures. This
is an important conclusion since the binding capacity of the coated product, in
some cases, is shown to be over 10-fold higher than the precursor polystyrene
scaffold (i.e., POROS R1 or POROS R2).
PMID- 9646495
TI - Comparison of diffusion and diffusion-convection matrices for use in ion-exchange
separations of proteins.
AB - A comprehensive study has been undertaken to characterise a range of
chromatographic properties for a series of modified polystyrene-divinylbenzene
(PS-DVB) chromatography matrices. The matrices studied included diffusion
matrices and matrices that allowed convective mass transfer of liquid into the
particles at high flow-rates, so-called "perfusion" matrices. The matrices tested
included the following: CG1000sd 20-50 microns (TosoHaas), PLRP4000s 15-25
microns, 50-70 microns (Polymer Labs.), Source 15RPC and 30RPC, 15S, 30S,
(Pharmacia Biotech), POROS 20SP type 1 matrix and OH activated POROS 20 type 2
matrix (PerSeptive Biosystems) and SP Sepharose Fast Flow (Pharmacia Biotech). A
Van Deemter equation was used to determine bead tortuosities and split ratios.
Frontal analysis, resolution studies, ionic capacities and isotherms were
measured. It was found that diffusion-convection chromatographic particles had
smaller plate heights to comparable diffusion particles. The smallest diffusion
bead, Source 15, had the lowest plate heights at low superficial velocities, but
the small particle size resulted in a high back pressure at high flow-rates. The
equilibrium binding capacities for lysozyme and IgG on the diffusion-convection
matrices were substantially lower than the equilibrium binding capacities on the
diffusion matrices. The dynamic capacities for these proteins were also lower on
the diffusion-convection particles, compared to the diffusion particles, over the
tested flow-rates. At high protein loading, resolution between proteins was
higher on diffusion particles than on diffusion-convection particles. Diffusion
convection particles showed low or no resolution at high protein loading. At
analytical level loadings, the diffusion-convection particles achieved a high
resolution over the whole flow-rate range tested and were more suitable for this
application than diffusion particles.
PMID- 9646496
TI - Determination of 1-nitropyrene with enzyme-linked immunosorbent assay versus high
performance column switching technique.
AB - An enzyme-linked immunosorbent assay (ELISA) on microplates and a HPLC coupled
column switching method were compared for the determination of the nitroarene
compound 1-nitropyrene in airborne particulate organic matter collected at a busy
intersection over a period of 2 months. After purification of the sample extract
with silica, in the multidimensional chromatographic method nitroarenes were
separated on a RP18 precolumn from matrix constituents followed by on-line
reduction to corresponding aminoarenes with a Pt catalyst on alumina and a
further separation of 1-aminopyrene on a second RP18 column. Methanol-water
(70:30, v/v) was the mobile phase used. With ELISA, a six-fold overestimation was
obtained for untreated samples. After clean-up it was lowered to approximately
1.6-fold overestimation which was mainly caused by cross-reaction of 2
nitropyrene and 2-nitrofluoranthene.
PMID- 9646497
TI - Identification of main corticosteroids as illegal feed additives in milk
replacers by liquid chromatography-atmospheric pressure chemical ionisation mass
spectrometry.
AB - Corticosteroids were proposed as growth promoting agents to improve commercial
quality of meat. We developed a liquid chromatography-atmospheric pressure
chemical ionisation mass spectrometry (LC-APCI-MS) method able to identify the
presence in milk replacers, when given by mouth, of dexamethasone, betamethasone,
flumethasone, triamcinolone, predinisotone, prednisolone, methylprednisolone,
fludrocortisone and beclomethasone, at levels in the range of 20-100 ppb. C18
solid-phase extraction, LC-RP C8 column separation, data acquisition (positive
ions) in the scan range m/z 200-550 allowed us to differentiate and identify
compounds by protonated molecules, their methanolic adducts and fragmentation
patterns.
PMID- 9646498
TI - Improved method for preparation and use of 9-anthryldiazomethane for
derivatization of hydroxycarboxylic acids. Application to diarrhetic shellfish
poisoning toxins.
AB - Application of a method for the "in situ" generation of 9-anthryldiazomethane
(ADAM) to the derivatization of the carboxyl function in diarrhetic shellfish
poisoning (DSP) toxins revealed the formation of artifact products. Using liquid
chromatography-mass spectrometry, it was determined that these artifacts were due
to base-catalyzed reactions between the solvent, ethyl acetate, and the hydroxyl
groups of the analyte to produce O-acetylated ADAM derivatives. Using a new
formulation, with tetrahydrofuran as solvent, it was possible to eliminate these
artifact reactions. Various reaction parameters have also been re-optimized to
ensure quantitative derivatizations. An assessment method was developed that was
useful not only for optimizing reaction parameters, but also for evaluating the
reagent potency before use on important samples. Finally, application of the
method to the determination of DSP toxins in plankton and mussel tissue was
demonstrated.
PMID- 9646499
TI - Determination of organoarsenicals in the environment by solid-phase
microextraction-gas chromatography-mass spectrometry.
AB - The development of a method for the analysis of organoarsenic compounds that
combines dithiol derivatization with solid-phase microextraction (SPME) sample
preparation and gas chromatography-mass spectrometry (GC-MS) is described.
Optimization focused on a SPME-GC-MS procedure for determination of 2
chlorovinylarsonous acid (CVAA), the primary decomposition product of the
chemical warfare agent known as Lewisite. Two other organoarsenic compounds of
environmental interest, dimethylarsinic acid and phenylarsonic acid, were also
studied. A series of dithiol compounds was examined for derivatization of the
arsenicals, and the best results were obtained either with 1,3-propanedithiol or
1,2-ethanedithiol. The derivatization procedure, fiber type, and extraction time
were optimized. For CVAA, calibration curves were linear over three orders of
magnitude and limits-of-detection were < 6.10(-9) M in solution, the latter a
more than 400 x improvement compared to conventional solvent extraction GC-MS
methods. A precision of < 10% R.S.D. was typical for the SPME-GC-MS procedure.
The method was applied to a series of water samples and soil/sediment extracts,
as well as to aged soil samples that had been contaminated with Lewisite.
PMID- 9646500
TI - Cell proliferation in chicken intestinal epithelium occurs both in the crypt and
along the villus.
AB - The location of cell proliferation and differentiation in chicken small
intestinal epithelium was examined using immunostaining, measurement of DNA
synthesis and brush-border enzyme activities. Chicken enterocytes were removed
sequentially from the villus using a modification of the Weiser (1973) method.
Alkaline phosphatase activity was relatively constant along the villus tip-crypt
axis but decreased in the crypt fractions, whereas sucrase and maltase activities
showed higher activity in the upper half of the villus and lower activity in the
lower half of the villus and in the crypt. Immunostaining of proliferating cell
nuclear antigen indicated the presence of proliferating cells both in the crypt
and along the villus, including some activity in the upper portion; the crypt
region exhibited a significantly higher number of proliferating cells. Labelled
thymidine incorporation into cell fractions after 2 h incubation exhibited a
similar pattern of proliferation, with the most active region observed in the
crypt and proliferation activity decreasing along the villus. However, some
activity was found in the upper half of the villus. After 17 h incubation, cells
from the middle region of the villi showed greater proliferation ability than the
2 h incubation. These results indicate that, unlike mammals, chicken enterocyte
proliferation is not localized only in the crypt region, and that the site of
enterocyte differentiation is not precisely localized.
PMID- 9646501
TI - The effects of cortisol and testosterone on renal function in male Antechinus
stuartii (Marsupialia).
AB - Seasonal changes in the physiology of Antechinus stuartii result in complete male
mortality after mating. The most important endocrine changes in males are large
rises in plasma testosterone and cortisol concentrations. Glomerular filtration
rate (GFR) in males declines coincident with high plasma testosterone and
cortisol. In the present study GFRs were measured in males captured in May (when
endogenous plasma testosterone and cortisol levels are low) and given depot
injections of either saline, testosterone-only, cortisol-only or testosterone
plus cortisol at doses designed to mimic plasma levels during the mating period.
GFR decreased significantly with testosterone injection, independent of cortisol
treatment. Urinary concentrations of sodium and chloride, and osmolality
decreased significantly with cortisol treatment, although the addition of
testosterone reversed the effect. Total urinary excretion of electrolytes was
similar between groups. Plasma potassium levels significantly increased in
testosterone plus cortisol treated males. Plasma sodium levels significantly
increased and plasma chloride significantly decreased in all groups treated with
cortisol. Water consumption significantly increased in all cortisol-treated males
and food consumption significantly increased in all testosterone-treated males.
The seasonal renal functional changes observed in A. stuartii were mimicked by
testosterone administration.
PMID- 9646502
TI - Analysis of parotid and mixed saliva in Roe deer (Capreolus capreolus L.).
AB - In ruminants, different functions have been ascribed to the different salivary
glands according to the feeding type. In this context, possible adaptations of
salivary functions were investigated regarding the secretion of various proteins
by different types of salivary glands. To yield uncontaminated parotid saliva in
large quantities, a non-surgical method has been developed. Parotid gland
secretions were collected via endoscopic placement of guide wires into each
parotid duct, which were subsequently used for placement of collection catheters.
Salivary flow was stimulated by intra-glandular administration of the
parasympathomimetic compound pilocarpine-hydrochloride into the parotid gland.
Mixed saliva (excluding parotid saliva) was collected into sterile tubes by
normal outflow during the sampling of parotid saliva. The total flow volume, flow
rate and the content of proteins as well as of several ions (Na+, K+, Ca2+,
inorganic phosphate) of both types of saliva were measured in sheep, fallow deer
and roe deer. Roe deer secreted the highest amount of total salivary proteins
relative to body mass [mg/kg body mass] and the highest relative volume [ml/10
min/kg body mass], both in parotid and mixed saliva, of all ruminant species
examined. Additionally, the protein profile and the tannin-binding properties of
parotid and mixed saliva in roe deer were investigated. Parotid saliva bound
almost twice as much tannin as mixed saliva, underlining the importance of
yielding uncontaminated parotid saliva for tannin-binding studies.
PMID- 9646503
TI - Metabolic suppression in anoxic frog muscle.
AB - Microcalorimetry is the only direct method for measuring moment-to-moment changes
in whole-cell metabolism (as heat output) during anoxia. We have adapted this
methodology, in conjunction with standard muscle isolation techniques, to monitor
metabolic transitions in isolated frog (Rana temporaria) sartorius muscle during
anoxia and recovery (reoxygenation). Anoxia (sustained 1 h, following 2 h
progressive hypoxia) suppressed muscle heat output to 20% of the stable normoxic
level. This effect was fully reversible upon reoxygenation. Metabolite profiles
were consistent with other anoxia-tolerant vertebrates--most notably, adenosine
triphosphate (ATP) content during anoxia and reoxygenation remained unchanged
from normoxia (pre-anoxic control). In addition, the concentration of K+ ions
([K+]) in interstitial dialysates remained stable (2-3 mM) throughout anoxia and
recovery. Interstitial [lactate-] increased slightly, in accord with anaerobiosis
supporting suppressed metabolic rates during anoxia. The degree of anoxic
suppression of metabolism observed is similar to other vertebrate models of
anoxia tolerance. Furthermore, stable ATP concentrations and interstitial [K+] in
the isolated tissue suggests that intrinsic mechanisms suppress metabolism in a
manner that coordinates ATP supply and demand and avoids the severe ion
imbalances that are characteristics of hypoxia-sensitive systems.
PMID- 9646504
TI - Behaviors and nutritional importance of coprophagy in captive adult and young
nutrias (Myocastor coypus).
AB - To estimate the contribution of coprophagy to protein intake, we observed the
behavior, particularly that associated with coprophagy, in adult and young
captive nutrias (experiment 1), and analyzed chemical composition and amino acid
composition, including diaminopimeric acid (DAP), an indication of bacterial
deprived protein, of soft feces, entire hard feces, and the black part and green
part of hard feces (experiment 2). Nutrias practiced coprophagy 48 times per 24 h
in adults, and 28 times in young animals, which not only had a 24-h rhythm but
also had 1-h or 2-h short-term rhythms. Nutrias ingested food and drank water
vigorously after sunset, following which they practiced coprophagy from midnight
to morning, before lying down for much of the day. When coprophagy was prevented
we sampled soft feces, produced from midnight to noon, which had high (P < 0.05)
concentration of crude protein (CP), DAP on a dry matter (DM) basis and 13 amino
acids on a 16 g N basis than hard feces, and had a low (P < 0.05) content of acid
detergent fiber (ADF). CP was greater in the black part than the green part of
hard feces (P < 0.05) although ADF was less (P < 0.05). The chemical composition
of the black part of hard feces was not significantly different from that of soft
feces. The dry weight of soft feces excreted in experiment 1 was 34.5 g and 9.7 g
DM per 24 h in adult and young animals, respectively. Using this value, the
contribution of soft feces to CP intake in adult nutrias was estimated as 16%,
superior to that obtained in rabbits for a diet with similar ADF concentration.
To Met and Lys intake the contribution of soft feces was 26% and 19%,
respectively in adult animals. These results suggest that coprophagy is quite an
effective manner for nutrias to ingest extra protein.
PMID- 9646505
TI - Muscle capillary supply in hind limb and diaphragm of the common shrew (Sorex
araneus).
AB - Shrew species of the subfamily Soricinae have unusually high metabolic rates when
compared to Crocidurinae shrews and other similar-sized mammals. The aim of this
study was to clarify whether the high basal metabolic rate of Soricinae shrews is
reflected in a high capillary density in their muscles. To this end, the
capillary supply of four limb muscles and diaphragm of the common shrew (Sorex
araneus) was quantified from cross-sectioned muscles. The capillary densities of
the limb muscles were 2575 +/- 329, 3111 +/- 299, 2812 +/- 197 and 2752 +/- 173
capillaries mm-2 fibre area in gastrocnemius lateralis, g. medialis, plantaris
and soleus, respectively. Capillary density of the shrew diaphragm (6691 +/-
1057) was double that of the limb muscles. This value is among the highest ever
measured in mammals. In general, the capillary supply in the hind limb of the
common shrew is about 3-4 times higher than commonly found in the leg muscles of
the laboratory rat or other bigger mammals, but similar to those in Crocidurinae
shrews and some small rodents. Thus the high resting metabolism of the common
shrew is not associated with an extraordinarily high capillary density. The
apparent disparity between basal metabolic rate and muscle capillary supply in S.
araneus is probably due to the small aerobic scope of shrews in the subfamily
Soricinae.
PMID- 9646506
TI - Characterization of a voltage-dependent conductance in the basolateral membrane
of leech skin epithelium.
AB - Voltage clamp studies were performed on the dorsal integument of Hirudo
medicinalis. Under apical calcium-free conditions an inward-directed component of
transepithelial current was activated by changes of transepithelial voltage.
Depolarization caused up to 50% increase of the transepithelial sodium current.
Hyperpolarization had no comparable effects. With calcium (1.8 mM) or amiloride
(100 microM) in the apical solution and in sodium-free solutions the inward
directed current failed to increase after depolarization. Activation also
occurred under chloride-free conditions. Permeabilization of the apical membrane
by nystatin (5 microM) increased the current activation significantly. After
nystatin, calcium as well as amiloride lost their inhibitory effects. This
indicates a basolateral localization of the voltage-dependent conductance.
Vesicle insertion or cytoskeletal structures are probably not involved in
regulation, as seen by the lack of effects of brefeldin A and the cytochalasins B
and D. However, serosal hyposmolar solutions (170 mosmol.1(-1)) caused a
reinforced activation of the current. Our results indicate a voltage-dependent
conductance in a tight sodium-absorbing epithelium.
PMID- 9646507
TI - Torpor patterns in the pouched mouse (Saccostomus campestris; Rodentia): a model
animal for unpredictable environments.
AB - Patterns of spontaneous and induced daily torpor were measured in the
Afrotropical pouched mouse (77-115 g), Saccostomus campestris, in response to
photoperiod, temperature, and food deprivation, using temperature telemetry.
Photoperiod had no influence on the incidence, depth, or duration of daily torpor
in either males and females. Although the testis size index decreased in response
to food deprivation and photoperiod by a maximum of 24%, full testis regression
did not occur. Torpor bout duration was, on average, 5.3 h, independent of
photoperiod and ambient temperature. Males did not enter torpor in response to
food deprivation but did in response to low ambient temperature, though
significantly less frequently than females. At normothermia, the body
temperatures (daily minimum, mean, maximum) of males were significantly lower
than those of females. Minimum body temperatures of both males and females during
torpor did not fall below 20 degrees C at an ambient temperature of 15 degrees C.
The patterns of torpor measured here differ from those observed in species from
strongly seasonal environments. They suggest adaptation to an environment
rendered unpredictable by the El Nino Southern Oscillations. As an aseasonal,
opportunistic breeder capable of year-round adaptive hypothermia, the pouched
mouse represents an excellent model animal for research on physiological and
behavioral adaptations to unpredictable environments.
PMID- 9646508
TI - The effect of infusion of hypertonic saline on glomerular filtration rate and
arginine vasotocin, prolactin and aldosterone in the domestic chicken.
AB - Domestic fowl were infused for 60 min with isotonic saline followed by 90 min
with hypertonic saline. Plasma electrolyte concentrations, osmolality and
haematocrit were measured. Urine electrolyte excretion rates, osmolar output and
urine flow rates were also monitored. From these results fractional excretions of
electrolytes were calculated. The renal function markers inulin and rho-amino
hippuric acid were infused to enable the measurement of glomerular filtration
rate and plasma clearance of rho-amino hippuric acid, respectively. Plasma
samples were also taken to assay for the hormones prolactin, aldosterone and
arginine vasotocin. Plasma electrolytes and osmolality, fractional excretion of
electrolytes and osmolar output all increased, while haematocrit decreased,
throughout the experiment. However, no significant change was found in urine flow
rate and little change was seen in glomerular filtration rate. The clearance of
rho-amino hippuric acid, which provides an indication of renal plasma flow,
increased during hypertonic saline infusion. Plasma concentrations of aldosterone
and prolactin decreased during the experiment and plasma concentrations of
arginine vasotocin increased. Infusion of hypertonic saline had no consistent
effect on glomerular filtration rate, which may be due to conflicting influences
of expansion of the extracellular fluid volume and increased plasma osmolality.
PMID- 9646509
TI - Pulmonary cryptococcosis due to a capsule-deficient strain confused with
metastatic lung cancer.
AB - A patient with hepatocellular cancer developed pulmonary cryptococcosis due to
infection with a capsule-deficient Cryptococcus neoformans. Pulmonary lesions
initially diagnosed as metastatic cancer by chest x-ray film and CT scan were
subsequently found to be fungal granulomas by autopsy. Although morphologic
studies of the fungi were insufficient to render a specific mycologic diagnosis
because of the absence of encapsulated yeasts, fluorescent antibody studies
confirmed the diagnosis of cryptococcosis. The use of various stains and electron
microscopy for the pathological differential diagnosis of cryptococcosis caused
by capsule-deficient yeasts is discussed.
PMID- 9646510
TI - Effect of sub-inhibitory concentration of chlorhexidine on lipid and sterol
composition of Candida albicans.
AB - The effect of a sub-inhibitory concentration of chlorhexidine on lipid and sterol
composition of Candida albicans was investigated. The total lipid content of this
yeast grown in the presence of chlorhexidine was reduced whilst the total sterol
content was increased compared with control-grown cells. Lipids and sterol
analyses of this yeast grown in the presence and absence of chlorhexidine are
presented. Chlorhexidine-grown yeast had a higher level of
phosphatidylethanolamine, phosphatidylcholine and monogalactosyldiacylglycerol.
Lower proportions of phosphatidylinositol plus phosphatidylserine, phosphatidic
acid and cardiolipin were found in C. albicans grown in the presence of the drug
when compared with control-grown yeast. The major fatty acids in control-grown
cells were C16 and C18. Drug grown-cells had higher proportions of palmitic acid
(16:0) and stearic acid (18:0), but lower proportions of palmitoleic acid (16:1)
and oleic acid (18:1). Chlorhexidine also decreased the unsaturated-to-saturated
fatty acid ratio, while the C16/C18 ratios increased compared to control-grown
cells. Differences in the fatty acid composition of major phospholipids and
neutral lipids between drug and control-grown yeast were also detected. Sterol
analysis of control-grown cells showed that the major sterol present was
ergosterol (55.4% wt). A significant increase in ergosterol and obtusifoliol was
observed in chlorhexidine-treated cells and a significant decrease in squalene
and lanosterol. Our results suggested that chlorhexidine affected the lipid and
sterol composition of C. albicans.
PMID- 9646511
TI - Preserved ascomatal and other fungal structures on the remains of a ninth century
Longobard abbess exhumed from a monastery in Pavia, Italy.
AB - Auxarthron californiense, Mixotrichum aeruginosum, Oncocladium flavum and
Chaetomium elatum were recognized on the basis of ascomatal structures on the
remains of a Longobard abbess who died in the IX century A.D. These fungi, which
had remained isolated in a crypt of the S. Felice Monastery of Pavia for almost
1000 years, are phenotypically identical to the type specimens. The occurrence of
these fungi and their ecological role are discussed.
PMID- 9646512
TI - Prevalence of otomycosis in malnourished children in Edo State, Nigeria.
AB - Out of the total number at 200 suspected cases of otomycoses consisting of 40
malnourished and 160 apparently healthy children examined in this study between
the months of July and August in Edo State, 64 Cases (32%) were identified to be
of fungal aetiology on the basis of positive culture and careful microscopic
examination. The state at protein energy malnourishment was deterwined using
physicians' comments in their case files. The fungal agents isolated were
Aspergillus niger 28 (43.8%); A. fumigatus 4 (25%); Fusarium solari 4 (6.3%);
Candida albicans 8 (12.5%); and Hendersonula teruloidea types torn B 5 (6.3%). Of
these isolates, A. niger having an solation rate of (43.8%) was found to be the
most predominant fungal species associated with otomycosis.
PMID- 9646513
TI - Experimental candidal mastitis in goats: clinical, haematological, biochemical
and sequential pathological studies.
AB - The present study, first of its kind, was conducted with the objectives to
understand hitherto little known aspects of candidal mastitis, like its
sequential pathology, pathogenesis and clinico-biochemical changes. For this
purpose, unilateral intramammary inoculation of 10 goats with Candida albicans
(1.2 x 10(7) yeast cells) resulted in the development of mastitis, with gross and
microscopic lesions being restricted to the infected udder halves only and
without dissemination of infection to the opposite uninfected udder halves as
well as other organs of the body. The experiment was continued for 40 days and
after infection, there was sharp fall in milk yield and Candida albicans was
directly demonstrated in the milk and re-isolated from the milk and udder tissues
up to 30th day after inoculation. An increase in total immunoglobulins in the
milk and plasma along with increase in total plasma proteins were also observed.
Haematology revealed leukocytosis and neutrophilia. Microscopically, there was
acute purulent mastitis, which later became chronic, nonpurulent and interstitial
with formation of granulomas. It was concluded that Candida albicans was highly
pathogenic to the lactating goat mammary gland even without immunosuppression or
antibiotic treatment, resulting in severe irreversible tissue damage and nearly
complete agalactia.
PMID- 9646514
TI - Temporal changes of 210Po in temperate coastal waters.
AB - The temporal variation of Polonium-210 (210Po) was examined in coastal sea water,
the mussel Mytilus edulis, the winkle Littorina littorea and green alga Ulva
lactuca in order to investigate the entry of 210Po into the marine food chain.
More than 99% of 210Po in the water column occurred in the particulate phase.
Dissolved 210Po concentrations peaked during the spring phytoplankton bloom and
it is suggested this is related to preferential scavenging of 210Po by the
increased numbers of bacteria, viruses and small dissolved particulates. Changes
in L. littorea 210Po specific activity are thought not to be related to food, but
to a drop in body weight following spawning. Much of the 210Po accumulated by M.
edulis was located in the digestive gland. The specific activity of 210Po in the
digestive gland of M. edulis was shown to be strongly correlated with changes in
sea water suspended particulate specific activity. Examination of other trace
metal (Ag, Al, As, Ca, Cd, Cr, Co, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Sb, Se, Sn and
Zn) variations in the digestive gland revealed that class B and borderline metals
had a strong positive correlation with 210Po. On-going work is investigating
whether the accumulation and loss of 210Po is affected by the presence of
metallothioneins.
PMID- 9646515
TI - Trace elements in the Korean coastal environment.
AB - The present article reports on the results of trace metal analysis in the Korean
coastal environment during the last decade. Trace metals of Cd, Cu, Pb and Zn in
seawater, sediments and mussels were determined in coastal areas of East, South
and Yellow Seas. Clean sampling, the use of ultrapure reagents, reference
materials and clean-room analysis were carried out to assure quality control. The
concentrations of trace metals in the Korean coastal environment were compared
with the results from other parts of the world oceans.
PMID- 9646516
TI - An overview of trace metal pollution in the coastal waters of Hong Kong.
AB - The state of metal pollution in Hong Kong's coastal waters has been assessed by
measuring metal levels in: (i) the water column; (ii) sediments and (iii) in
organisms, i.e. biomonitors. Current literature is reviewed. Data from sediment
analysis have shown that metal pollution is most severe in the urban areas of
Victoria Harbour, Tolo Harbour, Deep Bay and Northwestern waters. Bottom
sediments in typhoon shelters are particularly heavily polluted with, for
example, Cu levels from Kowloon Bay reaching 5300 mg.kg-1 in 1995. Since 1987,
levels of pollution have generally either stabilized or fallen in Deep Bay and
Victoria Harbour but have increased in Inner Tolo Harbour and Northwestern
waters. Many biomonitors have been used to study metal pollution in Hong Kong,
the most popular of which are barnacles, mussels (in particular Perna viridis)
and algae (in particular Ulva lactuca). Biomonitoring studies generally recorded
high levels of metal pollution in Victoria Harbour in the late nineteen seventies
and early eighties, with increasing pollution of the semi-enclosed Tolo Harbour
through the eighties and early nineties. In a recent study using barnacles, the
levels of Ag, As, Cd, Cu, Hg, Pb and Zn were shown to be greatly reduced as
compared to those recorded in 1986 and 1989, respectively. Levels of metal
pollution in Hong Kong coastal waters may have lowered in the last 10 years.
PMID- 9646517
TI - Field studies on imposex and organotin accumulation in the rock shell, Thais
clavigera, from the Seto Inland Sea and the Sanriku region, Japan.
AB - Field studies on imposex and organotin (butyltin and phenyltin) contamination in
the Japanese molluscs (the rock shell, Thais clavigera, and the Pacific oyster,
Crassostrea gigas) were conducted along the coast of both the Seto Inland Sea and
the Sanriku region, Japan, during February-March 1996. The percentage occurrence
of imposex in the rock shell, Thais clavigera, was still 100% at all sites
surveyed (22 and seven sites in the Seto Inland Sea and the Sanriku regions,
respectively). Observed values of the Relative Penis Length (RPL) index (%),
defined as the ratio of mean penis length in females to that in males, exceeded
50 at many sites. Sterile individuals whose oviducts were blocked by vas deferens
formation were also extensively observed. Tissue concentrations of organotin
compounds in the rock shell and the Pacific oyster were higher than those from
other areas of Japan. The degree of imposex (RPL index) was correlated with the
sum of TBT and TPT concentrations in tissue of the rock shell. Less recovery from
imposex in the rock shell and less amelioration of TBT pollution were observed,
suggesting that organotin use in antifouling paints has still continued for
vessels larger than 25 m in length and that it has influenced imposex symptoms in
the rock shell.
PMID- 9646518
TI - Uptake and depuration of 63Ni by Mytilus edulis.
AB - The uptake and depuration of Ni (as radioisotope 63Ni) by Mytilus edulis
(Mollusca: Bivalvia) has been investigated in a laboratory mesocosm. Nickel was
reversibly held on low energy surface sites of estuarine suspended particulate
matter (SPM), with a partition coefficient of the order 10(3) ml g-1, resulting
in approximately 80% of radioisotopic Ni being in the dissolved phase. Mussels
were fed a diet of radio-labelled estuarine SPM for 30 h in a flow-through
exposure period and for a further 24 h in a static exposure period. Following
exposure, the mussels were allowed to depurate in particle-free seawater.
Pseudofaeces and faeces were collected throughout the experiment and tissues were
dissected after 48 h of depuration. The 63Ni activity in the faeces was
approximately 50% of that in the feedstock SPM, while the activity in the tissues
was 2-29% of SPM activity. Tissue-specific accumulation occurred in the order
viscera > byssus > mantle > adductor muscle > gill > foot. The results are
discussed in the context of the bioavailability of Ni to mussels.
PMID- 9646519
TI - Biological monitoring of the impacts of the Ok Tedi copper mine on fish
populations in the Fly River system, Papua New Guinea.
AB - Monitoring of the impacts of the Ok Tedi copper mine on fish populations in the
Fly River system in Papua New Guinea has recorded approx. 100 species of fish
representing 32 families. Fish catches have shown considerable temporal and
spatial variability but, since the commencement of mine operations and the input
of mine-derived waste material into the headwaters of the system, long-term
monitoring has revealed significant reductions in fish catches at most riverine
sites in the Ok Tedi, upper and middle Fly River. However, no significant
declines in fish catches have been recorded in the lower Fly or delta areas.
Possible mechanisms accounting for the declines in fish catches in the river are
discussed. Although catches in some floodplain habitats have also declined, these
changes are thought to be associated with the effects of natural climatic
phenomena, particularly El Nino droughts. Introduced species and increased
commercial and artisanal fishing may also have had an effect. Levels of copper,
zinc, lead and cadmium were found to be elevated in tissues from a range of fish
species taken from riverine and floodplain sites sampled in the Ok Tedi and Fly
Rivers. Metal levels were generally much higher in liver and kidney than from
flesh. There was a general trend for metal concentrations to decrease with
distance downstream from the mine, suggesting a mine-related effect.
Significantly higher metal concentrations were recorded at 'impact' compared to
'control' sites. The intake of dietary copper by humans consuming fish taken from
the river is well within guidelines set by the World Health Organisation and does
not constitute a health risk. Ok Tedi Mining Limited has recently initiated a
programme of mitigation works aimed at reducing the adverse effects of mine
wastes on the river environment.
PMID- 9646520
TI - Accumulation of heavy metals in freshwater molluscs.
AB - Heavy metals in the aquatic environment have to date come mainly from naturally
occurring geochemical materials. However, this has been enhanced by human
activity such as gold mining in the case of heavy metal pollution in Sg Sarawak
Kanan. The high suspended solid loads in the river have quite efficiently removed
most soluble metals from the water and trapped them in the bottom sediment. Three
freshwater mollusc species were collected at the point source of the heavy metal
pollutants and analysed for the heavy metal contents in their tissues and shells.
Two of the mollusc species (Brotia costula and Melanoides tuberculata) are purely
freshwater species while the Clithon sp. nr retropictus is able to survive in
fresh and brackish water environments. The Brotia costula and the Clithon sp. are
the edible species which are sold in the market. Accumulation of As, Cu, Fe, Se
and Zn in all the three mollusc species were determined and the level of As in
the tissues of Brotia costula and the Clithon sp. was much higher than the
permissible level for human consumption. The mollusc species also demonstrated
different preferences for the uptake of different metals. Variations in the heavy
metal contents in the shell and tissues of the same species were also observed.
PMID- 9646521
TI - Comparison of metallothionein induction in response to cadmium in the gills of
the bivalve molluscs Mytilus galloprovincialis and Ruditapes decussatus.
AB - Metal binding characteristics and metallothionein induction differ markedly among
the gills of the bivalve molluscs Mytilus galloprovincialis and Ruditapes
decussatus exposed to sublethal cadmium concentrations (100 micrograms/l). The
rates of cadmium uptake as well as the percentage of cadmium bound to the cytosol
were significantly higher in the gills of M. galloprovincialis when compared with
that of R. decussatus. Similarly metallothionein concentration detected in the
gills of M. galloprovincialis increase fourfold while for the clam R. decussatus
metallothionein concentrations increased only twofold.
PMID- 9646522
TI - Haemocyanin and the binding of cadmium and zinc in the haemolymph of the shore
crab Carcinus maenas (L.).
AB - The trace metals cadmium and zinc are taken up from solution into haemolymph of
the shore crab, Carcinus maenas, where they bind to the respiratory pigment
haemocyanin. Investigations using FPLC and PAGE to separate the constituent
dodecamer and hexamer aggregations of haemocyanin showed a difference between the
distribution of cadmium and zinc between the two aggregate states. In the
haemolymph, labelled cadmium binds not only to haemocyanin but, at least
initially, it is also associated with low molecular size material or exists as
free cadmium ions. The binding of cadmium to haemocyanin is not an immediate
process. Initially the binding of cadmium favours the hexamer; only later is a
more even distribution between the two aggregate states apparent. Newly taken up
labelled zinc is rapidly bound to haemocyanin. The majority of both total and
labelled zinc in the haemolymph is bound to haemocyanin, with the hexamer having
a greater binding affinity for zinc than the dodecamer. This suggests that
formation of the dodecamer leads to a blocking of zinc-binding sites and/or that
the hexamer consists of subunits which possess a relatively high affinity for
zinc.
PMID- 9646523
TI - Effects of mercuric chloride and sodium selenite on some immune responses of blue
gourami, Trichogaster trichopterus (Pallus).
AB - The immunotoxicological effects of mercuric chloride and sodium selenite on blue
gourami were studied. Some immune responses ranging from non-specific to specific
were investigated. These include tissue lysozyme activity, kidney lymphocyte
proliferation and plasma agglutinating antibody titre against bacteria. After 2
weeks of chronic exposure, 0.09 mg/l of Hg2+ alone induced a significant increase
of kidney lysozyme activity of 4196.3 +/- 1171.0 U/g, but it decreased to 1577.4
+/- 902.4 U/g when exposed simultaneously to equiconcentration of selenium.
Plasma lysozyme activity was also increased by co-administration of Hg2+ and
SeO3(2-). The level of plasma agglutinating antibody against Aeromonas hydrophila
L37 was lowered in the chemical-treated fish. This indicates that the fish
immunity was impaired by action of mercury and selenium. However, the in vitro
lymphocyte proliferation test shows that mercury concentration lower than 0.045
mg/l Hg2+ enhanced the mitotic rate of kidney lymphocytes by approximately 30%. A
high concentration of mercury caused irreversible damaging effects on con A
induced lymphoblastogenesis. In contrast, the inhibitory effect of low
concentrations of mercury could be removed by washing. On the other hand,
selenium showed a suppressive effect on the lymphocyte proliferation even at 0.5
mg/l.
PMID- 9646524
TI - Hong Kong male subfertility links to mercury in human hair and fish.
AB - The focus of the present study was on the relationship between Hong Kong male
subfertility and fish consumption. Mercury concentrations found in the hair of
159 Hong Kong males aged 25-72 (mean age = 37 years) was positively correlated
with age and was significantly higher in Hong Kong subjects than in European and
Finnish subjects (1.2 and 2.1 ppm, respectively). Mercury in the hair of 117
subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than
mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm).
Subfertile males had approx. 40% more mercury in their hair than fertile males of
similar age. Although there were only 35 female subjects, they had significantly
lower levels of hair mercury than males in similar age groups. Overall, males had
mercury levels that were 60% higher than females. Hair samples collected from 16
vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or
meat for at least the last 5 years) had very low levels of mercury. Their mean
hair mercury concentration was only 0.38 ppm.
PMID- 9646525
TI - Trace metal pollution in Hong Kong: implications for the health of Hong Kong's
Indo-Pacific hump-backed dolphins (Sousa chinensis).
AB - The territorial waters of Hong Kong are highly contaminated with anthropogenic
pollutants, including trace metals. Hong Kong's population of Indo-Pacific hump
backed dolphins (Sousa chinensis) inhabits an area where a high volume of sewage
waste discharge and the close proximity of contaminated mud pits mean a
considerable potential for trace metal contamination. Trace metal concentrations
in the muscle tissue of fish caught from areas of high dolphin abundance are
notable. However, in order to gauge the amount of trace metal consumed by
dolphins, whole fish must be analysed. Whole fish from areas of high dolphin
abundance have considerably higher trace metal loads than muscle tissue alone.
Considering the consumption of prey items by dolphins, a daily intake of trace
metals was estimated as As, 410-518; Cd, 34-44; Co, 4-5; Cr, 40-50; Cu, 44-56;
Hg, 51-66; Mo, 22-27; Ni, 19-24; Pb, 320-403; Se, 99-125 and Zn, 388-490
(microgram kg-1 body wt. per day). Concentrations of arsenic, chromium, lead,
molybdenum and nickel in dolphin tissues were an order of magnitude lower than in
prey items, suggesting these elements may be excreted by this species. Mercury
concentrations in dolphin tissues were, however, an order of magnitude higher
than in prey items and could be considered potentially health threatening (max:
906 micrograms kg-1 dry wt.). Hong Kong's Indo-Pacific hump-backed dolphin
population has a high dietary intake of trace metals which may, especially in the
case of mercury, be a cause for concern.
PMID- 9646526
TI - Potential protective effect of calcium carbonate as liming agent against copper
toxicity in the African tilapia Oreochromis mossambicus.
AB - The lipid peroxidative effects of copper sulfate singly (4 mg/l CuSO4.5H2O) and
in combination with calcium carbonate (4 mg/l CuSO4.5H2O + 50 mg/l CaCO3) were
determined in the liver of the African tilapia Oreochromis mossambicus following
exposures of the fish to the chemicals for 24, 48, 72, 96 and 168 h. Lipid
peroxidative effects of the treatment with calcium carbonate (50 mg/l CaCO3) and
with a known hepatotoxicant, carbon tetrachloride (0.25 ml/l CCl4) were also
determined. Fish not exposed to any chemical served as negative controls. The
extent of lipid peroxidation was based on hepatic malondialdehyde (MDA) levels as
assayed using the thiobarbituric acid reaction test. Results suggested the lipid
peroxidative property of the copper salt which was associated with the toxic
nature of the heavy metal, although, this effect was not as potent as that of
CCl4. Findings also indicated a measure of protection against copper
hepatotoxicity provided by the addition of calcium carbonate as a liming agent in
the water.
PMID- 9646527
TI - Survey of trace elements in household and bottled drinking water samples
collected in Riyadh, Saudi Arabia.
AB - Total dissolved beryllium (Be), cadmium (Cd), chromium (Cr), copper (Cu), iron
(Fe), magnesium (Mg), manganese (Mn), mercury (Hg), nickel (Ni), selenium (Se),
strontium (Sr), vanadium (V) and zinc (Zn) were measured in the drinking water of
101 households and 21 samples of retail bottled waters purchased in Riyadh, Saudi
Arabia to ascertain the water quality for human consumption. The Inductively
Coupled Plasma Spectrometer (ICP) was used for analysis. First-draw Fe, Mn, Ni
and Zn concentrations decreased significantly after 10 min of flushing in the
morning. Cd, Fe, Hg, Ni and Zn in some cases exceeded the guideline limits
recommended by the EEC and WHO.
PMID- 9646528
TI - Hydrological studies of schistosomiasis transport in Sichuan Province, China.
AB - Schistosomiasis is a water-bourne parasitic disease endemic to Sichuan Province
of China. Long-term studies of infection and disease ecology in catchments in
Sichuan have been supplemented by detailed hydrometric measurements to produce a
model of water velocity and flow in an irrigation system. The model provides a
means of estimating travel times of two infectious stages of the parasite from
source sites to water contact exposure sites for individuals of both the human
population and the intermediate vector snail populations. The hydrological
transport model will be part of an overall model of schistosomiasis transmission
in the catchments. A GIS system is used to manage spatial data of the drainage
network, land use, infection sources and population centres. The development of
the Three Gorges Dam in China will increase marshlands and irrigation in areas
currently free of schistosomiasis. The potential for the spread of
schistosomiasis into these new areas is a major concern. Hydrological models can
be of particular importance in assessing future environmental risk.
PMID- 9646529
TI - QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and
carp.
AB - The toxicities of benzoic acids to Vibrio fischeri, Daphnia magna and carp were
measured. The results showed that the toxicity to V. fischeri and Daphnia
decreased in the order of bromo > chloro > fluoro approximately equal to
aminobenzoic acids. The toxicity of substituted benzoic acids to carp and Daphnia
was much lower that to V. fischeri. The results also showed that the toxicity of
benzoic acids to Daphnia decreased as the pH increased. It is suggested that
ionized and non-ionized forms have different toxic responses. The non-ionized
form may play an important role in toxicity because the toxicity of benzoic acids
to Daphnia greatly decreases as the pH increases. The toxicity of benzoic acids
to Daphnia may operate through non-polar narcosis, based on the regression
results between the toxicities and partition coefficients (log P) and apparent
partition coefficients (log D). However, toxicity cannot be predicted from non
polar baseline models because the ionized and non-ionized form of benzoic acids
have different contributions to toxicity. Compared with the single descriptors,
the prediction of toxicity of the benzoic acids was improved remarkably by using
log P with pKa and log P with ELUMO. For the toxicity of benzoic acids to V.
fischeri, it is suggested that the toxic mechanism may be different from the
mechanism in Daphnia and carp. A probable reason is that V. fischeri is a
unicellular organism with low lipid content, and hence both ionized and non
ionized forms of benzoic acids can easily cross the cell membrane and contribute
to toxicity.
PMID- 9646530
TI - Are nursery schools and kindergartens safe for our kids? The Hong Kong study.
AB - Pediatric heavy metal (particularly lead) poisoning is a widespread, yet
preventable problem in many parts of the world. Interior floor dust is found to
be one of the major pathways of childhood exposure. However, school and health
authorities in most countries do not have any stipulations nor guidelines in
regulating heavy metal contamination in floor dusts in schools. This study
attempts to examine the level of heavy metal contamination in 53 nursery schools
and kindergartens in Hong Kong and study its relationship with the environmental
factors. The results of this study reveal that the arithmetic mean level of lead
in exterior dust is 280.01 mg/kg, with a minimum level of 48.80 mg/kg and a
maximum of 2108.31 mg/kg, which is somewhat lower than other studies, such as
those reported by Chan et al. (Biomed. Environ. Sci. 1989;2:131-140) and Akhter
and Madany (Water Air Soil Pollut. 1993;66:111-119), but those of the manganese
(mean = 532.16 mg/kg, range = 102.51-1736.25 mg/kg) and zinc levels (mean =
2694.23 mg/kg, range = 898.33-9899.85 mg/kg) are much higher. Out of the 10
districts examined, Kwun Tong and North Point are found to be the most polluted.
They are older districts with polluting industries and heavy traffic. The results
of the analysis of variance suggest that the heavy metal particulate may
originate from the exterior. Auto-vehicles are a likely source. The toxins are
blown inside through the opened windows. Other factors that may affect the
content of metal in floor dusts are the time since the school was last painted,
the age of the housing complex, the condition of the school and the use of vacuum
cleaners.
PMID- 9646531
TI - Pesticides in stream water within an agricultural catchment in southern Sweden,
1990-1996.
AB - Pesticide loss to stream water was studied in a small agricultural catchment in
southern Sweden during the period 1990-1996. A total of 38 pesticides were
detected in water samples, including 30 herbicides, four fungicides, three
insecticides and one metabolite of one of the herbicides. Concentrations of
pesticides in stream water were observed throughout the sampling periods. Peak
concentrations occurred during the spraying seasons and following runoff events.
Daily average concentrations sometimes varied by one order of magnitude from one
day to another. Pesticides were also found in water samples as a result of
incautious actions during handling and application procedures. Concentrations
were lower at the outlet of the catchment area when the water had passed an open
part of the stream, compared to concentrations detected in discharge from a
culvert system upstream. This was largely a result of dilution from groundwater
intrusion during low-flow periods. Sampling at different sites along the culvert
demonstrated that the small village situated in the catchment did not contribute
to pesticide findings in the culvert discharge. Wind drift had little influence
on stream-water quality. Pesticide application for weed control in farmyards
resulted in a substantial contribution to the pesticide load in stream water.
Pesticide were persistent in the discharge throughout the winter and originated
from both autumn and spring applications, as well as from farmyard application.
Some autumn applied pesticides prevailed in stream flow during the following
summer. Total amounts of pesticides lost in stream flow during May-September each
year varied between 0.5 and 2.8 kg during the 7-year period, corresponding to
approximately 0.1% of the applied amount. Losses of single pesticides were
generally less than 0.3% of the applied amount during individual years.
Pesticides from agricultural applications in the catchment constituted, on
average, 82% of the total transported amount lost during May-September each year,
of which 2% was from autumn application the previous year. There was an overall
correlation between amounts used in the catchment and occurrence in the water
samples. The total pesticide load in water decreased markedly during the course
of the investigation, in accordance with decreased amounts applied during spring
and early summer. The results indicate that concentrations of some pesticides
entering head-water streams in agricultural areas are close to, and during
certain time periods even above those levels demonstrated as having an impact on
the aquatic flora and fauna.
PMID- 9646532
TI - Trace element reference values in tissues from inhabitants of the European Union.
X. A study of 13 elements in blood and urine of a United Kingdom population.
AB - Electrothermal atomic absorption spectrophotometry (ETAAS), inductively coupled
plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA) were used
for the quantitative determination of 13 trace elements in urine and seven trace
elements in whole blood of healthy unexposed British subjects living in three
regions of the United Kingdom. Careful control of pre-analytical and analytical
factors have enabled the results obtained from more than 200 individuals to be
used in proposing reference intervals for the following elements; Al, As, Cd, Co,
Cr, Cu, Hg, Mn, Mo, Ni, Pb, Se, Tl in urine, and Cd, Cr, Hg, Mn, Pb, Se and Tl in
blood.
PMID- 9646533
TI - Imaging assessment before surgical resection.
AB - The improvement of preoperative imaging techniques gets hepatic surgery easier
making it more safer and effective. The authors describe the most common hepatic
pathologies, benign and malignant, pointing out for each one the principal
diagnostic appearances achievable with, the several techniques and, collating
these last between them, they optimize the diagnostic-curative pathways for
several pathologies. Beyond allowing the diagnosis of the lesion's nature, an
important role of the imaging modalities is also to evaluate the resectability of
single lesion, weighing up its exact location and the impact on the vascular
system esteeming, finally, the volume of remnant liver in case of larger
resections. The intra- and extrahepatic, preoperative staging, of the varied
hepatic lesions, primitive and secondary, performed comparing the most modern
diagnostics techniques, results to be dramatically important arterial portography
during, CT (CTAP), contrast-enhanced helical CT, MR imaging. For each patient
it's possible to plan the most adequate treatment to his pathology.
PMID- 9646534
TI - Preoperative portal embolization.
AB - Excess parenchymal loss associated with hepatectomy is the leading risk
factor/for liver failure especially in patients with impaired hepatic function.
Selective portal embolization (PE) before hepatectomy is aimed to induce an
atrophy of the embolized lobe to be resected, with a compensatory hypertrophy of
the/counterlobe to be preserved. We performed PE followed by hepatectomy in 58
patients with hepatocellular carcinoma (HCC, n. = 44) or metastatic liver tumour
(MLT, n. = 14). All the patients well tolerated PE, and hepatic functional data
returned to the baseline levels within a week. The left lobe volume increased by
about 10% after the right PE. Hepatectomy procedures undertaken comprised right
or extended right lobectomy (n. = 39), central bisegmentectomy (n. = 3), extended
segmentectomy (n. = 12), and limited resection (n. = 4). The 25 of HCC patients
underwent right-sided lobectomy despite a presence of hepatic functional
impairment, and the 3 of MLT patients under went right lobectomy with additional
resection of the left lobe. As a whole, the operative morbidity and mortality
rates were 15.5% and 1.7%, respectively (one patient died of liver failure). The
5-year over all survival rates were 46.8% in HCC patients and 38.0% in MLT
patients, respectively. Preoperative PE therefore can be an ancillary procedure
for patients, despite with hepatic dysfunction or with bilobar tumours, who may
need extensive hepatectomy.
PMID- 9646535
TI - Clinical application of ultrasonography in liver surgery.
AB - Modern liver surgery is based upon deep knowledge of the surgical anatomy of the
liver and improvements with ultrasounds imaging techniques have provided
multidimensional interpretations of the liver anatomy intraoperatively. The
technical advances with real-time scanning combined with the pioneering efforts
of the Japanese liver surgeons have permitted the dynamic adaptation of the
functional liver anatomy to the real anatomy, thus intimately aiding in segment
oriented anatomical resection. Intraoperative ultrasound afford several
advantages such as viewing the internal anatomy in direct relationship to the
surface landmarks under the probe, enabling higher frequencies resulting in
greater image resolution. The utilization of intraoperative ultrasound can modify
the tactics involved with resection of both primary and metastatic liver tumours.
The routine use of intraoperative ultrasound is strongly advocated since more
complex procedures can be performed safely since the surgeon proceeds with
complete knowledge of the real liver anatomy when deciding the feasibility and
extent of liver resection.
PMID- 9646536
TI - Hepatic resection: perioperative course and management.
AB - Normal liver can tolerate even a right trisegmentectomy with caudate resection
which results' in a reduction of liver volume by 80%, while a decompensated
cirrhotic liver cannot tolerate even partial hepatic resection. This can be
ascribed to decreased functional volume and the deterioration of individual
hepatocyte function, which is caused and amplified by inappropriate
intraoperative procedures and postoperative management. Problems related to liver
diseases, including liver cirrhosis, jaundice and chronic active hepatitis,
operative techniques and postoperative management should be considered during
hepatic resection. Pathophysiology and tactics for handling these problems will
be described.
PMID- 9646537
TI - Vascular occlusion techniques for liver resections.
AB - Prevention of intraoperative blood loss during liver resection is of prime
concern. Intraoperative blood loss has indeed repeatedly been shown to adversely
influence the short-term prognosis of patients undergoing liver resection. There
is in addition evidence that it could be associated with an increased risk; of
recurrence in patients operated for an hepato-biliary malignancy through
impairment of the patient's immune response. The prime concern of the hepato
biliary surgeon is to minimize blood loss through the control of the major
vascular structures this may be achieved in several ways that range from
segmental portal control to total hepatic vascular occlusion. The type of
vascular occlusion should be selected according to the indication and in
particular location of the tumour and presence of an associated underlying liver
disease, the patient's cardiovascular status and the experience of the operator.
Aim of the authors is to describe the various types of vascular control as well
as their benefits and drawbacks so as to use the most appropriate technique
according, to each patient' requirements.
PMID- 9646538
TI - Repeated hepatectomy for colorectal metastasis.
AB - Between January 1981 and December 1995, 12 patients, who previously underwent
hepatic resection for colorectal metastases, were selected for a second liver
resection for isolated liver recurrence. Mean interval between first and second
resection was 16 months. Eight patients had solitary and 4 multiple metastasis.
Two major hepatectomies and 11 wedge resections were performed. Mean follow-up
was 37 months. No mortality and 33% morbidity was observed. Three and 5-year
actuarial survival rates were 71% and 42%, while disease-free survival was 30%.
No patient, primary tumour, or metastases' characteristics were significantly
associated to survival. Surgical resection is the only therapy that could offer
reasonable chance of long term survival and, in selected case, of cure. A careful
patients' selection as well as an accurate surgical technique are essential to
reduce post operative mortality and morbidity.
PMID- 9646539
TI - Hepatic resective surgery in cirrhotic patients. Techniques and results of
anatomical segmentectomies.
AB - The paper describes the technique of anatomical liver segmentectomies based on
the extraparenchymal clamping, at the hepatic hilum, of the afferent vascular
pedicles. The resection is started on the liver surface along the demarcation
line caused by the ischemia. During parenchymal transection the technique of
hemihepatic vascular occlusion has been undertaken. The results obtained with 125
segmentary hepatic resections performed for hepatocellular carcinoma arised on
cirrhosis are also reported. The overall operative mortality has been 6.4%. The
actuarial 1 and 3 year survivals were 93.3% and 70.4% respectively. Hepatic
segmentary resections are recommended for limited hepatic lesions, mainly in well
compensated cirrhotic patients.
PMID- 9646540
TI - Hepatic resections through the laparoscopic approach.
AB - Hepatic surgery has been undergoing progressive modifications in surgical
approach to liver, passing through tohraco-phrenolaparotomy to bilateral
subcostal incision and current Makuuchi's. Laparoscopic liver surgery should not
be considered a new surgery, but simply a new surgical approach, with
difficulties but advantages too. Laparoscopic hepatic resections are feasible
with low morbidity and mortality; the short and medium term results are
comparable to those obtained with open surgery provided that the surgeon has a
significant experience in open hepatic surgery, advanced laparoscopic surgery and
the availability of all and pertinent instrumentation. The aim of this paper is
to show the rationales formal of hepatic resections through the laparoscopic
approach, focusing on the necessary instrumentation, the surgical technique and
results.
PMID- 9646541
TI - [Cervical neurinomas. (Considerations in five cases operated in Day-Surgery)].
AB - We report the experiment of five cases of neurinoma observed in the division of
Day Surgery of the Third Surgery Clinic, operating in the Hematology Institute of
University of Studies "La Sapienza" in Rome. The problems of the diagnosis of
this neoplasia has been faced, though it is commonly unknown or confused with
other cervical especially lymphonodules tumefactions, from which it is almost
impossible to distinguish before the operation. In the period of six years on 775
cases of cervical neoformations have been operated only 5 patients bearers of
neuromi; two originated from vago cervicale (right and left), one from simpatico
cervicale on the left, another from the left spinal accessory and the last from
the secondary medial trunk of the left brachial plexus. All the patients have
been operated in Day-Surgery anaesthesia, locoregional and with calming of
spontaneous breath. One case, that originated from the secondary medial trunk of
the left brachial plexus, has been operated with microsurgical technique. On all
the cases has been done a subcapsular exeresis to preserve nervous continuity. No
post operating complications have been recorded; all the patients discharged in
the evening. The diagnosis about the nature is left to the final histological
test on the operating piece. The surgical removal remains even today the elective
treatment able to exclude probable relapses and potential malignant
transformation of these tumours.
PMID- 9646542
TI - [Acute abdominal pain in emergency surgery. Clinical epidemiologic study of 450
patients].
AB - A retrospective study on 450 patients admitted in emergency with acute abdominal
pain in a general surgical unit of the Ist Institute of Surgery of the University
of Rome "La Sapienza" was carried out during a 7 years period. The aim of the
study was to identify the most frequent causes of acute abdominal pain correlated
with age, sex, onset of pain and other conditions in order to improve diagnosis
and reduce mobility for mortality. Appendicitis was the most frequent diagnosis
(75 pts = 16.4%). Non-specific abdominal pain (NSAP), found in 71 pts (15.5%),
cholelithiasis in 57 pts (12.5%), abdominal malignancy in 47 pts (10.3%) were
other frequent conditions. The largest number of admissions occurred in the age
groups 60-70 years (16.6%) and 20-30 years (14.2%). Surgical operations were
performed in 206 patients (45.7%). The overall mortality was 4.2% (19/450 pts)
and the rate increased significantly in patients aged > 60 years. Postoperative
mortality was 5.8% (12/206 pts) while mortality rate in non-operated patients was
2.8%. The causes of perioperative death included perforated peptic ulcer,
abdominal malignancies (15.4%) and urgent colonic resections (9.4%). The duration
of inpatients stay increased significantly with the age of the patients,
including those with nsap. The results of the study indicate a need to review the
methods of diagnosis of appendicitis and to obtain a better clinical performance
in patients with nsap.
PMID- 9646543
TI - [Surgical techniques in ruptured abdominal aortic aneurysm].
AB - In recent years we are observing an increasing number of authors. The surgical
results, in the elective cases, are improved drammatically, and now, in many
Centers, the mortality rate is less than 5%. We haven't observed the same
improvements for the emergency cases. In this setting the mortality rate is still
around 50% or more. What we are facing, however, is the changing of the clinical
picture of this patients. In the most part of cases, the patient dies in the
Intensive Care Unit, after a long and complex post-operative course, and not more
in the Operating Room. Still, this could be considered a good result, expression
of a better surgical experience. The way to obtain higher survival, at the
moment, is linked to a better understanding of the physiologic derangements in
the Intensive Care Unit. The authors discuss the organizative and technical
changes the permitted to achieve this results.
PMID- 9646544
TI - [Short bowel syndrome: etiologic, pathogenetic aspects and principles of
treatment].
AB - A significant problem in surgery following massive intestinal resection is the
short bowel syndrome characterized by severe fluid and electrolyte loss, watery
diarrhoea and malnutrition. Total parenteral nutrition and enteral nutrition are
essential in the clinical course of the syndrome; their use for prolonged periods
results in the gradual intestinal adaptation and greater absorptive and reservoir
capacities of the intestinal remnant. Adjunctive surgery can slow rapid
intestinal transit and induce growth of neo-small-bowel mucosa but is not
recommended for routine use. The early results of intestinal transplantation in
the treatment of short bowel syndrome are encouraging. Furthermore chronic
rejection and systemic sepsis with failure of the graft must be considered and
indicate that at present this procedure cannot be offered to every patient but
will be a potential form of therapy in future.
PMID- 9646545
TI - [Reoperations in surgical oncology: recurrence of colon carcinoma after surgery].
AB - Colon cancer is the second leading cause of death for cancer disease, after lung
cancer, with nearly 18,000 deaths per year in Italy. In spite of the progress
that have taken place over the past 30 years, little improvement has been gained
in this dismal outcome, and the 5-year survival remains around 50%. Over one half
of the patients will suffer from recurrence after a potentially curative
resection. A major challenge lies in better detection of recurrences in order to
diagnose those patients still amenable to curative resection. Locoregional
recurrence is of particular interest and its frequency, diagnostic limitations
and surgical treatment are herein discussed.
PMID- 9646546
TI - [Morbidity after video-laparoscopic cholecystectomy in cholelithiasis associated
with liver cirrhosis. A case-control study].
AB - At present laparoscopic cholecystectomy represents the treatment of choice for
symptomatic cholelithiasis. Authors performed a retrospective case-control study
to evaluate whether cirrhosis associated with cholelithiasis increases the risk
for morbidity of laparoscopic cholecystectomy. Twenty-one patients with
cholelithiasis and cirrhosis (Child-Pugh class A or B) (group A) and 21 controls
with cholelithiasis without cirrhosis (group B) entered the study. Controls were
paired with cases for age, sex, and indication for cholecystectomy (simple
cholelithiasis, acute cholecystitis). The two groups were compared for rate of
conversion to open cholecystectomy (19% group A vs 9.5% group B; p = 0.31),
morbidity (29.5% group A vs 5.3% group B; p = 0.17), median length of surgery (80
m in the two groups), and median time of postoperative hospitalization (5 days
group A vs 3 days group B; p = 0.21). No difference among variables resulted to
be statistically significant. Besides, neither common bile duct injuries nor
intra or postoperative hemorrhages occurred in patients with cirrhosis. Authors
conclude that the laparoscopic cholecystectomy can be considered a safe and
effective surgical procedure also for patients with cholelithiasis associated
with cirrhosis with a good residual hepatic function.
PMID- 9646547
TI - [Leiomyosarcoma of the small intestines: case reports].
AB - Intestinal malignant neoplasms are extremely rare (1% of all solid tumours) and
leiomyosarcomas represent 20% of them. The authors report the experience of 5
cases (M:F ratio = 0.6), aged 30-69 yrs old, treated in the period 1985-95. The
best results have been obtained in 2 cases, characterized by low grading and
submitted to curative resections. The others presented local and distant (mostly
hepatic) extensions with a poorer prognosis (1-3 yrs. survival). Leiomyosarcomas
are particularly binding because of their rarity and aspecific symptomatology,
determining late diagnosis in most cases. The clinical course, the surgical and
complementary management, the istology and the prognosis have been analysed.
Nowadays 5 yrs-survival is very low and the prognosis remains severe because of
local and distant metastases, already present at laparotomy. New chances may come
out from better diagnostic techniques and from new complementary
chemotherapeutical associations.
PMID- 9646548
TI - [Laparoscopic treatment of biliary cysts].
AB - Here comes presented three cases of biliary cysts treated with laparoscopic
technique. In the first case the discovery of a single cyst of small size on the
hepatic margin have consented the total removal. In the second case was about a
voluminous unique cyst, while in the third has been found an hepatic
polycystosis. In both of them has been applied Lin's procedure with
videolaparoscopic technique.
PMID- 9646549
TI - [Laparoscopy in iatrogenic lesions of the colon during operative endoscopy].
AB - Colonscopy is a standard diagnostic and therapeutic procedure that has its own
morbidity. Colonic perforation is the dangerous complication of this procedure.
Successful management of perforation by conservative or surgical treatment
remains controversial. We report two cases, recently observed, of patients with
colonic perforation occurring during therapeutic colonscopy treated with
minimally invasive technique.
PMID- 9646550
TI - Further studies on Trypanosoma mukasai HOARE, 1932 and its biological vector
Batracobdelloides tricarinata (BLANCHARD, 1897).
AB - Trypanosoma mukasai from the blood of Clarias lazera was successfully transmitted
to eight fresh water fish species using B. tricarinata as vector. Such cross
transmission showed that the trypanosome was not host specific. Previously
described fish trypanosome species were morphologically indistinguishable, and on
the basis of the present result they were regarded as a single species, T.
mukasai. Trypanosomes increased in size the longer they remained in fishes and
they were observed for up to 7 months in surviving fishes. In B. tricarinata,
they survived over a period of 10 months involving 18 meals after the initial
blood meal, provided the fasting period did not exceed 28-80 days. Survival was
attributed to residual stages in the crop. The population ecology of B.
tricarinata revealed an increase of the total population and of brooding of eggs
and/or youngs during spring and summer. Although, the leech fed on a broad
spectrum of hosts, certain fishes such as Chrysichthys auratus were preferred.
Also, certain sites (e.g. the head in C. auratus) were preferred to others. The
amount of blood ingested varied from two to about three times its body weight.
Time for digestion of blood was dependent on the size of the leech as well as the
species of the fish. The histopathological changes at the attachment sites of
leeches were studied.
PMID- 9646551
TI - [Urinary calculi in small and other animals--a retrospective study of the years
1980-1989].
AB - More than 500 uroliths from dogs, cats, minks, rabbits and 9 further animal
species originating from various regions of former East Germany were analysed.
The observations were made between 1980 and 1989 using X-ray diffraction and
infrared spectroscopy. The urinary stones consisted of struvite, whewellite,
weddellite, cystine, ammonium urate, brushite, whitlockite, hydroxyapatite or
carbonate-apatite, calcium carbonate, silicon dioxide and organic matrix stones.
In dogs, the most frequent types were struvite and apatite concrements, followed
by calcium oxalate and cystine uroliths. Among the diseased animals poodles,
dachshunds and terriers ranked first. In the analysed material from cats apatite
and struvite predominated. With few exceptions, minks formed struvite uroliths
only. The analysed calculi from rabbits consisted principally of calcium
phosphate or calcium carbonate concrements. The present analysis has been
compared with results of former studies, differences are discussed.
PMID- 9646552
TI - Adjuvant properties of killed Propionibacterium avidum KP-40 in vaccination of
dogs against canine parvovirosis.
AB - Immunomodulating and adjuvant properties of Propionibacterium avidum KP-40 (PA),
a potent stimulator of the macrophage-monocyte system and inducer of endogenous
interferon, were tested in healthy dogs and in dogs vaccinated against canine
parvovirosis (CPV). A single subcutaneous injection of PA (0.5 mg/kg b. m.) was
administered either 10 days before or simultaneously with CPV immunization. The
immunomodulating properties of PA were expressed by enhancement of phagocytic and
bactericidal activities of blood leukocytes, accompanied by elevated serum levels
of interferon-gamma and interleukin-1 and higher Con-A-induced transformation
rates of lymphocytes. Titres of CPV antibodies were significantly (p < 0.01)
higher in dogs vaccinated and treated with PA either 10 days prior to or
simultaneously with immunization. It is concluded that PA may be applied as a
potent and safe adjuvant in vaccination of small animals and additionally, it
provides enhancement of non-specific antibacterial and antiviral resistance of
the organism.
PMID- 9646553
TI - Uterine androgen receptor mRNA expression in metestrous and anestrous bitches
being healthy or suffering from Pyometra.
AB - The importance of androgens for the female reproductive system has been
investigated for decades and a number of androgen sensitive processes has now
been identified in female reproductive organs. For carnivore species no data were
available so far about uterine androgen sensitivity and its regulation. The
present study therefore aimed to investigate whether androgen receptors (AR) are
present in the dog uterus, whether they are regulated throughout the ovarian
cycle and whether pyometra affects their expression rate. Uterine tissue samples
were collected from 28 bitches of different ages and various breeds. The samples
were grouped according to the stage of estrous cycle (metestrus ME or anestrus
AE) and the pathological status of the uterus (i.e. suffering from pyometra or
not). Androgen receptor mRNA (AR mRNA) was quantified from 500 ng of total RNA
isolated from the tissue samples using an internally standardized reverse
transcription polymerase chain reaction (RT-PCR) described previously. The amount
of total RNA extractable per g tissue was elevated during pyometra. The
successful amplification of the expected 172 bp fragment from canine uterine RNA
together with the confirmation of the identity of this fragment by sequence
analysis, demonstrates that AR is expressed in this particular tissue. Comparing
the expression rates in uteri from bitches during ME or AE being healthy (H) or
suffering from pyometra (P), the only significant (p < 0.01) difference was found
between H and P uteri during ME with 3.5-fold lower expression rates in P.
Although the same seems true for AE bitches, a significant difference could not
be demonstrated due to the low number (n = 2) of diseased animals in the AE
group. There was no evident effect of the stage of ovarian cycle on uterine AR
mRNA levels.
PMID- 9646554
TI - Alterations in peripheral blood leukocytes functions during enzootic
bronchopneumonia of calves. Effect of treatment with antibiotics and
immunomodulators.
AB - Twelve calves from over veal calf farm were divided into two groups: group I-6
calves which developed typical signs of enzootic bronchopneumonia and group II-6
calves with no symptoms of the disease. Both groups of calves were compared with
respect to changes in several hematological parameters. Some functions of
peripheral blood leukocytes as random migration, phagocytic index, percent of
phagocytic cells and percent of NBT positive cells were also scored. In addition,
changes in serum levels of interferon (IFN) and tumor necrosis factor (TNF) and
the ability of peripheral blood leukocytes (PBL) to produce IFN and TNF were
quantitated by biological methods. On the day of diagnosis, in group I of calves
a significant increase in the total serum protein concentration, hemoglobin
content, red and white blood cells counts in comparison to control calves (group
II) was observed. The increased number of NBT positive neutrophils and moderate
levels of serum IFN and TNF correlated with elevated body temperature, breathing
and heart rates. Calves with bronchopneumonia (group I) after diagnosis of the
disease were treated with Tylbian (tylosine derivative), Flumetazon
(glucocorticoid), Emulselvet (immunomodulator), bromhexinum and sulphonamides.
Seven days after the beginning of treatment with medicaments a significant
improvement in clinical symptoms was observed, however, the ability of PBL to
cytokine production increased significantly 2 weeks after beginning of treatment
and correlated with significant increase in random migration of neutrophils and
their phagocytic activity, measured by the percent of phagocytic cells.
Unexpectedly, in control calves (group II), not exhibiting any symptoms of
bronchopneumonia at the beginning of experiment, high serum IFN titers were
detected which decreased significantly during the first week of observation. In
contrast to that the ability of PBL of control calves to produce IFN increased
significantly within 3 weeks of observation. The correlations between the ability
of PBL to produce cytokine and the development of clinical symptoms of
bronchopneumonia are discussed.
PMID- 9646555
TI - Colonization capability of orally administered Lactobacillus strains in the gut
of gnotobiotic piglets.
AB - In the present study, the effect of Lactobacillus casei subsp. casei and
Lactobacillus fermentum inoculation on jejunum and ileum colonization in
gnotobiotic piglets has been observed. The characteristic features of the strains
used were strong adherence to pig epithelial gut cells as well as inhibitory
activity against enteropathogenic E. coli under in vitro conditions. Strains were
inoculated to 2, 3, and 4 day old gnotobiotic piglets at a dose of 2 ml (1 x
10(8) germs/ml). On the second day after the last inoculation, Lactobacillus
casei subsp. casei strain counts adhered to the jejunum mucosa and those adhered
to the ileum mucosa were 4.54 log 10.cm-2 and 5.40 log 10.cm-2, respectively.
Lactobacillus fermentum counts adhered to the jejunum mucosa and those adhered to
the ileum mucosa were 5.73 log 10.cm-2 and 4.01 log 10.cm-2, respectively. On day
5 after the last inoculation, the counts in both strains were by one log higher.
The results obtained point out to the fact that Lactobacillus casei subsp. casei
and Lactobacillus fermentum colonized the mucosa of both jejunum and ileum and
survived in the intestinal tract. The adherence of lactobacilli to gut cells in
vitro correlated with their capability to adhere to the mucosa of both jejunum
and ileum in vivo.
PMID- 9646556
TI - [Clinical-virologic course after superinfection of persistently infected cattle
with cytopathogenic bovine viral diarrhea virus strains].
AB - Vaccination with live cytopathogenic (cp) bovine viral diarrhoea virus (BVDV) is
often used for control of this disease. In animals which are persistently
infected with noncytopathogenic (ncp) BVDV this can lead to the outbreak of
mucosal disease (MD). To simulate vaccination of such animals and to monitor the
clinical-virological course after superinfection, nine clinically healthy calves
which were persistently viremic were superinfected with different cp BVDV
strains. One animal succumbed to early onset MD within three weeks after
superinfection. During the observation period of 18 months four animals developed
severe clinical signs. While two animals developed late onset MD, the other two
had to be euthanized due to clinical signs which could not be related to the
superinfecting BVDV. These results indicated that after superinfection or
vaccination of persistently infected calves with cp BVDV the probability of
developing early and/or late onset MD is significantly increased. The risks
arising from uncritical vaccination of herds with unknown virological status in
relation with the control of BVDV conforming to the actual official guidelines
are discussed.
PMID- 9646557
TI - [Group B Streptococcus infections: new forms. New preventive measures].
PMID- 9646558
TI - [Seroprevalence versus Parvovirus B19 in blood donors].
AB - BACKGROUND: The aim of the study was to describe the seroprevalence against
Parvovirus B19 in a random sample of blood donors in the Hospital Universitario
de Salamanca. METHODS: We studied the presence of IgG and IgM antibodies against
Parvovirus B19 in 136 sera from asymptomatic blood donors by enzyme immunoassay
methods. RESULTS: From 136 samples tested, 88 (64.7%) had positive absorbance
values for IgG. Forty eight samples (35.5%) were negative. IgM was negative in
all cases. We did not find indeterminate results. DISCUSSION: Parvovirus
primoinfection usually happens in the childhood. Thus, we can expect a high
percentage of general population to have antibodies against Parvovirus B19. Anti
Parvovirus B19 antibodies prevalence in blood donors was 64.7%. This failure is
similar to data reported before (65%). Clinical importance of these viruses in
currently related with hemathopoyesis diseases and with the possible role in
theratogenesis. The presence of IgG seems to give protection except in some
chronic infections recently described.
PMID- 9646559
TI - [Cytomegalovirus: comparative study of diagnostic techniques].
AB - BACKGROUND: The aim of this study was to undertake a comparative study of a
series of diagnostic techniques of active infection by cytomegalovirus (CMV) in
blood (isolation of CMV by shell vial, detection of specific anti-CMV IgG and
IgM, antigenemia-detection of pp65 antigen by staining with peroxidase- and two
variants of qualitative polymerase chain reaction [PCR]-conventional PCR or in
one step and nested PCR-for detection of viral DNA). METHODS: Fifty kidney
transplant patients were followed for the first 6 post transplant months. All
except 6 were seropositive for CMV prior to transplantation and only one
seronegative patient had a seronegative donor. RESULTS: A total of 750 blood
samples were analyzed, 8 of which were positive by shell vial, 91 by specific IgM
detection, 115 by antigenemia, 225 for conventional PCR and 440 for nested PCR.
No positive sample was detected throughout follow up by any of the techniques
used in only 4 patients (one being the seronegative receptor with a seronegative
donor). CONCLUSIONS: Antigenemia was found to be the fastest, cheapest and
simplest method of diagnosing CMV, presenting the advantage of providing
quantitative results which allow the establishment of a relationship with the
appearance of symptomatic infections. With the two variants used qualitative PCR
was observed to be the earliest and most sensitive technique, while being the
most difficult and the most expensive, with the disadvantage that its great
sensitivity limits its clinical usefulness.
PMID- 9646560
TI - [Prevalence of human immunodeficiency virus infection in drug addicts assisted
from 1991 to 1996 at a detoxification center in Castilla y Leon].
AB - BACKGROUND: The Word Health Organization (WHO) has recommended epidemiologic
surveillance of infection by the human immunodeficiency virus (HIV) in high risk
populations. An important decrease has recently been observed in the prevalence
of HIV infection in drug addicts in different regions in Spain with notable
differences being found. The evolution of the prevalence of HIV infection in
intravenous drug addicts initiating detoxication in Castilla and Leon was
analyzed. METHODS: Six hundred forty-seven drug addicts (535 males and 112
females) were studied over 6 years (1991-1996) analyzing HIV seropositivity,
demographic variables, drug use, age of initiation in drug consumption and route
used. RESULTS: Most of the drug addicts were males (83%) with a mean age of
initiation in the use of drugs of 19.6 years. Heroine was most frequently
consumed in 95% of the patients. The mean length of consumption on admission was
8.6 years with no significant differences being observed in sexes. A relationship
was observed between HIV infection and the lower age of initiation in drug usage
with the greater the age of admission to detoxication the longer the time having
consumed drugs. The prevalence of HIV infection significantly decreased in males
and females from 36.8% in 1991 to 17.4% in 1996 (p < 0.0005), with this decrease
being related to the change from the intravenous to the smoked route of drug
intake. On multivariate analysis by logistic regression the odds ratio at one
year of admission was significant (OR = 0.80), years of drug addiction (OR =
1.15), intravenous route (OR = 3.04) and female sex (OR = 2.75). CONCLUSIONS: A
significant decrease has been observed in the prevalence of HIV infection in drug
addicts in Castilla and Leon attending a therapeutic center for detoxication from
1991-1996.
PMID- 9646561
TI - [Chronic necrotizing pulmonary aspergillosis: infrequent form of aspergillosis].
AB - BACKGROUND: Chronic necrotizing pulmonary aspergillosis (CNPA) is a chronic
pulmonary infection caused by the genus Aspergillus, which usually involves
moderately immunosuppressed patients. METHOD: We describe 3 patients with a toxic
syndrome that had lasted several weeks or months, with lung infiltrates in the
chest X-ray and the CT scan. Mycobacterium tuberculosis could not be isolated
from different respiratory smears (sputum, bronchoaspiration, Barlett catheter
and pulmonary punction in the third case). Moreover, there was no response to
anaerobic treatment. RESULTS: All 3 patients were moderately immunosuppressed (2
men were COPD and the woman was an asthmatic patient). One of the men was being
treated for a nocardiosis. In all three cases, A. fumigatus was isolated from de
different respiratory smears. CONCLUSIONS: To diagnose a CPNA, a high degree of
clinical suspicion is needed. The differential diagnose should be done with
pulmonary tuberculosis and anaerobic infections. The presence of a member of the
genus Aspergillus in the tracheobronchial secretions of a patient should not be
systematically considered a saprofit, specially when other microorganisms can not
be isolated.
PMID- 9646562
TI - [Methods for evaluating diagnostic tests in Enfermedades Infecciosas y
Microbiologia Clinica].
AB - BACKGROUND: In the field of infectious diseases and clinical microbiology, the
evaluation of diagnostic tests (DT) is an important research area. The specific
difficulties of this type of research has motivated that have not caught the
severity methodological of others areas of clinical research. This article try to
asses and characterize the methodology of articles about DT published in
Enfermedades Infecciosas y Microbiologia Clinica (EIMC) journal. METHODS: Forty
five articles was selected in the EIMC journal during the 1990-1996 period,
because of determinate the sensitivity and specificity of different DT.
Methodological standards, extensively accepted was used. RESULTS: In all of
articles, except one (98%) the gold standard was specified yours use, however in
4 studies (9%) include the DT in the gold standard (incorporation bias). The
correct description of DT was reported in 75% of cases, but only in 11% cases the
reproducibility of test was evaluated. The description of source of reference
population, standard of inclusion and spectrum of composition was described in
58, 33 and 40% of articles, respectively. In 33% of studies presented workup
bias, only 6% commented blind-analysis of results, and 11% presented
indeterminate test results. Half of the studies reported test indexes for
clinical subgroups, only one article (2%) provided numerical precision for test
indexes, and only 7% reported receiver operating characteristics curves.
CONCLUSIONS: The methodological quality of DT research in the EIMC journal may
improve in different aspects of design and presentation of results.
PMID- 9646563
TI - [Assessment of 4 commercial immunoenzymatic assays for the serologic diagnosis of
Helicobacter pylori infection].
AB - BACKGROUND: The aim of this study was to evaluate four commercial tests for the
serologic diagnosis of infection by Helicobacter pylori based on the detection of
IgG class antibodies versus this microorganism. METHODS: Four commercial kits
were analyzed based on the ELISA method in serum samples of 48 patients admitted
for digestive endoscopy. The data of the serologic tests were compared with those
provided by the culture, the histologic observation and the urease test of
gastric biopsy specimens. The calculation of seroprevalence of anti-H. pylori
antibodies in serum of 60 asymptomatic subjects was carried out. RESULTS: The
seroprevalence of infection by H. pylori in an asymptomatic population of between
18 to 78 years of age was 58.33%. A sensitivity of 94.3% and a specificity of
88.9% were observed with the Pyloriset EIA-G test. The positive predictive value
(PPV) was 92.2% and the negative predictive value (NPV) 91.5%. With the
Chemifarma commercial kit the sensitivity was 78.8% and the specificity 100% with
a PPV of 100% and NPV of 76.7%. Plate showed a sensitivity of 85.3% and a
specificity of 87.5% with a PPV of 90% and a NPV of 80.76%. Milenia had a
sensitivity of 80% and a specificity of 66.7% and a PPV of 77% and a NPV of
70.7%. CONCLUSIONS: The usefulness of the serologic tests for the diagnosis of
Helicobacter pylori infection is herein confirmed with the test evaluated showing
a high sensitivity and specificity as well as high predictive values.
PMID- 9646564
TI - [Diabetic foot: a path leading to avoidable amputation].
PMID- 9646565
TI - [Painful costal tumor in an HIV-positive patient].
PMID- 9646566
TI - [Cutaneous nodules and arm paresthesia].
PMID- 9646567
TI - [Retrommamary abscess caused by Nocardia asteroides in HIV-positive patient].
PMID- 9646568
TI - [Mycobacteria retrieval with the MB-Check system].
PMID- 9646569
TI - [Hematogenous osteomyelitis of the tibia caused by Eikenella corrodens].
PMID- 9646570
TI - [Nephrogenous diabetes insipidus secondary to the administration of amphotericin
B and liposomal amphotericin B].
PMID- 9646571
TI - [Hip septic arthritis as presentation form of acute appendicitis].
PMID- 9646572
TI - [Wound infection caused by Vibrio parahaemolyticus].
PMID- 9646573
TI - [Thyroiditis caused by Pneumocystis carinii in a patient with HIV infection].
PMID- 9646574
TI - [Ocular infection caused by Aeromonas spp.: considerations on its treatment and
importance of resistance to antimicrobial agents].
PMID- 9646575
TI - [Antibodies against prolactin in patients with systemic lupus erythematosus and
hyperprolactinemia].
AB - We investigated patients with lupus erythematosus to detect the presence of
hyperprolactinemia and to determine it's origin. From the seric specimens
obtained in 225 patients with LES, we found 37 (14.5%) with hyperprolactinemia
and they were trated with polyethylenglicol, in 11 of 37 patients (29.7%) had a
high significance of prolactin precipitation (PRL). The test in gel filtration
shown the big-big PRL (Molecular weight > 100 kDa) was the predominant form from
PRL seric in these patients and no woman had clinic effects of hyperprolactinemia
as galactorrhea and/or amenorrhea. The big-big PRL essence was due to an
antibody, with it was found like a immune complex (Ig-PRL). This evidence suggest
the patients with LES and hyperprolactinemia have a very high incidence of
macroprolactinemia relationated to antibodies anti-PRL, and in spite of the
hyperprolactinemia not have clinical effects like amenorrhea and/or galactorrhea,
and it is other cause to explain the high incidence of hyperprolactinemia in
patients with LES.
PMID- 9646576
TI - [Radiologic, densitometric, morphologic and electron microscopic study of
osteoporosis and osteopenia in the third lumbar vertebra in men and women in the
city of Mexico].
AB - OBJECTIVE: To determine bone density in the third lumbar vertebra in a group of
men and women from the Mexico City correlating the morphometric characteristics
of vertebral body by specific techniques and to detect groups with alterations
like osteoporosis or osteopenia. METHODOLOGY: The study was made in third lumbar
vertebra from 23 patients dead of the Medical Service Forense-Mexico, 8 women
between 31 to 72 years old and 15 men between 25 yo 62 years old. The studies
were: Radiological, bone densitometry and by image in which was determined
density of vertical and horizontal trabeculaes. With x-ray technique in scanning
electron microscopy was determined in form semiquantitative the presence of Ca,
P, Mg and Na, and Ca distribution by technique of x-ray energy dispersed.
RESULTS: In the radiological trail all vertebras of the female group were
abnormal, the major finding was degenerative feature; 5 Showed trabeculation
increased 3 fractured; in the males group 7 patients were normal, degenerative
fracture in 8; of these six had densitometry with DEXA; in the females group only
one was normal, 3 osteopenia, 5 osteoporosis; in the male group: 5 osteopenia and
5 osteoporosis. Scanning electron microscopy examination exhibit a homogeneous
and dense expression pattern, wherever SEM demonstrated the absence or decrease
of deposit calcium in osteoporosis. A morphometric examination of the trabecular
thickness demonstrates a difference between the two sexes. The normal median was
222.1 microns, the osteoporosis range was 126.3 to 156.2 microns in the female
osteoporosis, in male group was found two normal values with a trabecular density
mean of 249.7 microns, in the last two cases one with osteopenia and the other
with osteoporosis, the mean value was 186.4 microns. CONCLUSIONS: In the present
study, was demonstrated that the degenerative alterations in osteoporosis and
osteopenia in young people are more frequent to respect other reports. The
following observations require special emphasis either because they provide clues
to the mechanism of altered expression of calcium: Genetic, ethnic, consume,
sedentary and others.
PMID- 9646577
TI - [Apoptosis and extracellular matrix degradation in chorio-amnion during labor and
premature membrane rupture].
AB - BACKGROUND: The molecular mechanisms of chorioamniotics membranes rupture during
labor are relationated with a group of enzymes named metalloproteinases of
extracellular matrix (MMP), the production of these enzymes are elevated in
premature rupture of membranes. The collagenase IV (molecular weight 92 kDa) is
induced in specific form during both events. We unknown the regulatory mechanisms
to these enzymes in the chorioamnios. OBJECTIVE: To determine the presence of
apoptosis and expression of (MMP-) in human chorioamnios during the labor and
premature of the fetal membranes. MATERIAL AND METHODS: The gel lysis using
zimography was determined in membranes of 1) Labor, 2) Cesarean section, 3) PRM.
The analysis of DNA fragmentation in situ and DNA of the membranes was studied.
Using immunohistochemistry techniques was identified MMP-9. RESULTS: It was
observed increase of gel lysis in stracts with PRM and labor in comparation with
cesarean section. In all the specimens were found apoptotics cells, however, they
were scareces, abundance or very abundance in cesarean section specimens, labor
or PRM respectively. The fragmentation in situ was confirmed in specimens of DNA.
The immunohistochemistry showed positively to MMP-9 in labor and PRM specimens,
and not in cesarean section specimens. The MMP-9 immunorreactivity was extensive
in PRM and only was found apoptosis. CONCLUSIONS: The results demonstrate that
apoptosis and expression-activity of MMP-9 can be associated to membranes rupture
during labor and lysis, the same explanation may be true for the increased
expression of MMP-9 in PRM both phenomena seems to have a sequence.
PMID- 9646578
TI - [A new parameter for the evaluation of premature luteinization: the pre-ovulatory
molecular relation between serum concentrations of progesterone and estradiol].
AB - The objective was to evaluate the molecular ratio between the serum levels of
progesterone (P) and estradiol (E2) and to determine it's effect on the in vitro
fertilization performance. Sixty two couples were studied, the molecular P:E2
ratio was established the day of human chorionic gonadotropin (hCG) injection.
The mean serum P concentration the day of hCG administration 1.45 +/- 0.50 ng/mL,
while the mean P:E2 ratio was 0.63 +/- 0. Pregnancies were observed since
molecular ration of 0.22, no pregnancies were obtained if the molecular ratio was
> 1.02. No significant difference was detected in the fertilization and pregnancy
rates in the patients who have or not premature luteinization. The implantation
rate was low in patients with premature luteinization, however, there was not
significant difference with patients without premature luteinization. In
conclusion, the P:E2 ratio surrounding 1.0 is desirable to obtain adequate
results in in vitro fertilization programs. In this work as others, the premature
luteinization do not have effect in the reproductive results.
PMID- 9646579
TI - [Ovum donation: a 3-year experience at the Gynecologic and Obstetric Center of
Monterrey, Mexico].
AB - OBJECTIVE: Evaluating the rate of pregnancies, neonates, implantation rate and
kinds of donor in our program Assisted Reproduction with oocyte donation.
INTRODUCTION: The oocyte donation is the most important support in assisted
reproduction because in patients with ovarian failure, offering the same
opportunity to female without ovarian alterations to increase the rate of
pregnancies. MATERIAL AND METHOD: 98 donor's procedures were included in host
patients; 87 were FIV-TE and 11 GIFT between march to june 1997. The patients
were divided in age group: 1) < 30 years, 2) 30 to 34 years, 3) 35 to 39 years,
4) > or = 40 years. The donors were divided in known (26) and unknown (72). The
results were analysed. RESULTS: 48 pregnancies (55.17%) of the 87 FIV-TE-D group
were obtained with 31 neonates The implantation rate was 17.5% to FIV-TE group
and 13.8 to GIFT group, 44 (61.11%) pregnancies were from unknown donors group
and 9 (34.61%) from known donors group. CONCLUSIONS: Our results are similar to
others international reports, we have observed a little and significative
difference between pregnancy with oocytes from known donors and unknown donors;
this is the principal motive to be selective in the suitable known donor.
PMID- 9646580
TI - A dose of prevention.
PMID- 9646581
TI - Two automated perimeters.
PMID- 9646582
TI - UCB's 75th anniversary: Cal's proud legacy of the twentieth century provides new
promise at the millenium.
PMID- 9646583
TI - Essentials in fitting ocular prostheses for complex congenital and acquired
anomalies.
AB - BACKGROUND: Providing ocular prosthetic services is an important aspect of total
patient care. A patient who has lost an eye to injury, inflammation, or tumor
experiences emotional and psychological trauma similar to that experienced by an
amputatee. Congenital absence also creates a special set of circumstances. A
prosthesis that is lifelike in appearance is a comfort to the patient, and the
physical wearing comfort becomes a primary prerequisite for the patient. CASE
REPORTS: A variety of congenital and acquired anomalies are used to illustrate
the clinical application of modern-day materials used to fabricate and fit ocular
prostheses. A comprehensive evaluative protocol is also presented. CONCLUSION:
New materials and better fitting techniques allow more patients to wear
prostheses greater comfort and cosmetic approval. The primary care optometrist
should be familiar with the options available to the patient and the standard of
care in evaluation of patients who wear a prosthesis.
PMID- 9646584
TI - History of contact lenses at the University of California, Berkeley, School of
Optometry.
PMID- 9646585
TI - Berkeley optometry: clinical training into the 21st century.
PMID- 9646586
TI - Sports medicine and the eye care professional.
AB - BACKGROUND: There are more than 40,000 eye injuries every year in the United
States--many of which are sports-related. Sports injuries are a common cause of
severe vision loss. Today, contact sports, racket sports, and other high-risk
athletic activities are more popular on an organized and informal level. Those
engaging in these activities should wear the proper eye and facial protection, so
as to minimize the risk of severe injury and potential vision loss. CASE REPORTS:
Case studies are used to illustrate examples of sports-related clinical
experiences encountered in a primary care practice. A description of protective
devices, a discussion of product liability, the standard of care, and the
doctor's responsibility to the patient complement the case scenarios. Emphasis is
placed on prevention and particular attention should be paid to the patient at
high risk and to the one-eyed patient. CONCLUSION: Sports-related eye injuries
have a high risk for ocular morbidity and subsequent severe vision loss. Many
sports related injuries are preventable and the primary care practitioner can
provide important information and education regarding protection and avoidance
for those participating in high-risk activities. The provider should promote
compliance and be adequately informed as to product liability, standards,
manufacturers of the devices, and indications for the use of specific devices.
PMID- 9646587
TI - "Health care law and politics: failure of patient care", a view since 1995.
AB - To eliminate the budget deficit in seven years, the Congress of the United States
is engaged in revising thirty years of American health care policy. Medicaid
health benefits for 30 million low-income disabled (of which 46% are children)
would be turned into a state-by-state block grant, with virtually total
individual state discretion to determine eligibility and covered services.
Medicare, providing health care for 37 million elderly, is about to change the
fee for service system into organized cluster systems of managed care.
PMID- 9646588
TI - An unusual case of wrongful pregnancy: liability of doctor resulting from
misrepresentation.
AB - A married woman and her husband recovered damages from a gynaecologist after the
woman gave birth to a third and normal child. The couple's second child had been
delivered by way of Caesarean section. Six days after its delivery the doctor
made the statement (erroneously) that he had performed a tubular ligation on the
woman, following a discussion on the advisability of sterilisation. In fact no
such procedure had been performed. The woman became pregnant again. The doctor
was held liable on the basis of a negligent misrepresentation.
PMID- 9646589
TI - Evidential damage as a result of improper medical records.
AB - The article provides a summary of the development and definition of the cause of
action described by the Israeli courts as "evidential damage". This cause of
action stems from the duty placed on health care providers to keep proper,
complete and accurate records of diagnoses and medical treatments administered to
patients. This duty was first developed by the courts and then recently codified
in the Patients' Rights Law passed in 1996. Initially the courts in Israel
recognised that the failure to keep proper medical records could only shift the
burden of evidence from the plaintiff to the defendant, but the requirement to
show negligence still remained. Eventually the courts recognised that the failure
to keep proper medical records, in itself could bar a plaintiff's ability to
prove his claim, and therefore they determined this to be an independent cause of
action, which can be compensated to the extent of the damage caused by the
medical incident which was not properly documented.
PMID- 9646590
TI - Intended blinders in research.
AB - It could be argued that science is the only generally recognised cognitive
authority in the world today. Science is not constrained by frontiers between
countries. The art of science is influenced by more factors, how entrenched ideas
govern scientific beliefs, also by talent, trends, politics, lobbying, peer
review, priority, conflict of interest etc. Therefore what might have occurred in
concealment, is of common scientific interest. An actual example from Denmark is
presented showing how research into patients rights and consumer protection has
been employed as a technical stumbling-block by health authorities. The
authorities problem was certainly a political, not intrinsically a practical
medical or scientific one.
PMID- 9646591
TI - Deaths on the table: proposal for an international convention on the
investigation and prevention of anaesthetic mortality.
AB - National and international variations in clinical practice, study methodologies,
and data collection make the estimation of patient deaths attributable in some
measure to anaesthesia a difficult task. Such rates have undoubtedly
significantly declined, a tribute, in large part, to the work of groups such as
the International Committee for the Prevention of Anaesthetic Mortality and
Morbidity, the Anesthesia Patient Safety Foundation and the Australian Patient
Safety Foundation. There is, however, internationally, still a significant risk
of mortality associated with anaesthesia which is distinct from that related to
any relevant surgery or intercurrent disease. As a matter of pure logic, patients
worldwide should be entitled to expect a basic minimum of knowledge and skills
from an anaesthetist, as well as his or her use of standard monitoring equipment.
In an age where the global provision of health services and equipment may be
increasingly dominated, under trade-promoting international agreements, by a few
trans-national corporations, and where technology facilitates dissemination of
medical data, a unified, worldwide approach to the investigation and prevention
of anaesthetic mortality appears both rational and urgent. The benefits of an
investigatory system, focused on subsequent safety rather than present liability
and standardized through International Conventions, are well established in the
air transport industry. We urge the involvement of persons with political and
legal expertise in the development of an International Convention for the
Investigation and Prevention of Anaesthetic Mortality.
PMID- 9646592
TI - Forensic urology: a practical vision.
AB - Urologists enjoying the protection of the law owe a duty to participate in the
legal system as expert witnesses. Forensic education has been neglected by
clinical educators. Qualification of experts includes forensic as well as
clinical competence. The forensic urologist must know legal concepts and
language; the powers, duties, and role of courtroom experts. The expert witness'
role is to factually enlighten the judges, not to persuade them. Practical
measures to remedy the current state of affairs are described from over a decade
of experience. These practical measures should be supplemented by the formal
development of a subspecialty of Forensic Urology sponsored by our colleges and
professional societies.
PMID- 9646593
TI - Maternal weight and fetal injury at birth: data deriving from medico-legal
research.
AB - The relationships among maternal weight, gestational weight gain, fetal birth
weight and birth injuries have been investigated in connection with 62 cases of
shoulder dystocia that involved permanent impairment of the newborn or neonatal
demise. A high prevalence of > 13.5 kgs. gestational weight increase between the
first and last office visits (62%) obesity expressed as > or = 87 kg. body weight
at term (64.1%) and > or = 4000 gm. birth weight (80%) was found in this group of
patients. The results indicate that the relationship between excessive maternal
and fetal body weights and shoulder dystocia related fetal or neonatal impairment
is closer than previous studies have suggested. These results underline the
importance of appropriate and intensive nutritional counselling of the mother
throughout pregnancy, noting that arrest of the shoulders is only one of those
obstetric complications that are closely related to maternal obesity. The
findings underline the usefulness of medico-legal reviews in clinical research.
PMID- 9646594
TI - Forensic psychiatric evaluation: clinical, ethical and procedural issues in South
Africa.
AB - Evaluations done by the Forensic Psychiatrist take place in relation to various
situations and in circumstances of a statutory nature and include clinical
assessments for treatment, management and rehabilitation. Numerous issues in the
field of legal process and ethical dilemmas are discussed. Conflicts with the
traditional role occur and continued awareness of this is relevant for the
maintenance of standards in the whole of psychiatry. Advocacy for better
conditions for mentally ill offenders and consultation with state legislatures
regarding changes in the criminal justice system and other relevant procedures
are recommended. This is most significant especially for the indigent defendant
and to allay public issues of the client referred, as well as those who
ultimately become patients.
PMID- 9646595
TI - Transinstitutionalization and an overburdened judicial system.
AB - The author discusses punishment in the United States in the context of increasing
transinstitutionalization. He believes that the administration of justice has
become more complex, in part because of plea bargaining and pleading reforms,
often does not allow the application of judicial fairness, and has lost its
deterrent effect on criminal offenders. He proposes the necessity for a
reorganization of the roles of the various social institutions.
PMID- 9646596
TI - Late termination of pregnancy in cases of severe abnormalities in the fetus.
AB - Developments in medical technology have increased the possibility of diagnosing
severe structural abnormalities in the fetus. In such circumstances, the woman
may request termination of her pregnancy. This raises serious ethical and legal
questions, in particular if the abnormalities are discovered after 24 weeks of
gestation, when the fetus is considered viable. This article discusses the legal
aspects of this problem, with particular reference to the Netherlands. If one
accepts that, in exceptional circumstances, third trimester abortion may be
justified on medical grounds, the law should make provision for it. However, the
general protection provided by the law to fetal life-especially in the third
trimester--should remain firmly in place.
PMID- 9646597
TI - Artificial reproduction and the family of the future.
AB - The techniques of artificial reproduction have until fairly recently been geared
to overcoming male sterility by means of AID and IPSI and female sterility by way
of GIFT, VISPER and DIPI. The above techniques have concentrated on achieving
conception either within or without the uterus. Gestation has always been
completed in utero and the therapy was reserved for married couples. The above
circumstances only required limited legal regulation and its effect on the family
unit was minimal because the child was mostly conceived from the gametes of its
parents New technologies which are looming on the horizon, however, threaten to
change the concept of parent and family radically. I refer to the imminent
perfection of the artificial uterus and the cloning of human cells. If these
technologies are sanctioned, a child would be conceived from the cells of one
parent only and will not be gestated within the mother's womb. How will society
and the law react to these technologies? Will they regulate them or proscribe
them? I will argue in favour of the former rather than the latter.
PMID- 9646598
TI - Case consultation: ablatio penis.
AB - In male infants, traumatic ablation of the penis, with or without loss of the
testicles may occur as a sequel to mutilatory violence, accidental injury, or
circumcision error. Post-traumatically, one program of case management is
surgical sex reassignment to live as a girl, with female hormonal therapy at the
age of puberty. The other program is genital reconstructive surgery to live as a
boy, with male hormonal therapy at puberty if the testicles are missing. In both
programs, the long term outcome is less than perfect and is contingent on
intervening variables that include societal ideology; surgical technology;
juvenile and adolescent timing and frequency of hospital admissions construed by
the child as nosocomial abuse; development of body image; health and sex
education; fertility versus sterility; coitus and orgasm; possible lesbian
orientation if living as a girl; and long-term cost accounting, including the
psychic cost of being a pawn in possible malpractice litigation on whose
disability a very large fortune in compensation may devolve. There is, as yet, no
unanimously endorsed set of guidelines for the treatment of genital trauma and
mutilation in infancy, and no provision for a statistical depository for outcome
data.
PMID- 9646599
TI - Informed consent and extended operations.
AB - This article concerns the extended operations or procedures where during an
operation, previously agreed between surgeon and patient and while the patient is
anaesthetised, the surgeon realizes that further or totally different measures
should be, or may be taken. In this contribution the author defends a strict
point of view concerning "extended operations". If during the operation, the
surgeon discovers that other measures should be taken, he may proceed if there is
an emergency. A more pragmatic view would violate the right to self
determination.
PMID- 9646600
TI - Outcomes of regular versus extended outpatient alcohol/drug treatment. Part II.
Medical, psychiatric, legal and social problems.
AB - Alcohol and drug patients were placed into two groups in order to study
differences in outcome based on treatment duration. One group received regular
outpatient treatment of 90 days (n = 103), and the other received extended
outpatient treatment of 180 days (n = 127). Most patients received 30 days of
inpatient stabilization treatment before placement into outpatient. METHODS:
Patients were randomized into the two groups, and interviewed at discharge, and
three and six months post-discharge. Data were analyzed using chi-square, t-test,
and multivariate logistic regression techniques. RESULTS: There were no major
differences between the two groups in the numbers reporting subsequent drug use,
or medical, psychiatric, legal, and social problems. However, in terms of
ancillary effects, the extended treatment group had slightly more desirable
outcomes with respect to doctor's visits, arrests, or being a homemaker at three
and six months post-discharge. Post-discharge medical problems, in terms of
doctor's office visits, were predictable by longer treatment duration, pre
treatment cocaine use as primary drug, and pre-treatment heroin use as secondary
drug. Patients were most likely to live with parents, roommates, or alone.
Whereas abstinence was related to stability in living arrangements, aftercare
attendance and heroin use were related to unstable living situations.
PMID- 9646601
TI - [From obstacles, to become a good pharmacist].
PMID- 9646602
TI - [Treatment of post-traumatic headaches. Recommendations of the German Migraine
and Headache Society].
PMID- 9646603
TI - [Diagnostic procedures in venous thrombosis of the legs].
PMID- 9646604
TI - [Venous thromboembolism. Anticoagulation and thrombolysis].
PMID- 9646605
TI - [Vomiting after the first trimester of pregnancy: an alarming symptom].
AB - Nausea and vomiting are common problems of pregnancy. Three pregnant women, 27,
25 and 28 years of age, presented with vomiting in the third trimester. The
causes appeared to be maternal small bowel volvulus, which was derotated after
primary caesarean section, an ileocecal abscess, which was the first
manifestation of Crohn's disease, and acute pyelonephritis, treated with
cefuroxim. The second and third babies were born spontaneously; no maternal or
foetal mortality occurred. Persistent vomiting after the first trimester of
pregnancy should be considered an alarm symptom which always requires further
investigation.
PMID- 9646606
TI - [Notes on the visitation of medical schools in 1997].
AB - The members of the Visitation Committee who audited the medical education process
in the Netherlands carefully formed their opinions based on a vast amount of
information. Their judgement can be considered fair and well-balanced. Several
critical remarks were made, especially on the coaching of students during their
internships. The scientific education was also found wanting. Some faculties were
given bad marks, and scores of recommendations were made. Surprisingly, however,
the committee was of the opinion that students graduating from all faculties were
equally and sufficiently competent to enter the medical workforce. It is
recommended that next time this audit process be carried out on a much smaller
scale.
PMID- 9646607
TI - [Immunology in medical practice. IV. Mechanisms in the development of primary
nephropathies].
AB - Humoral immunological reactions play a central part in the development of
nephropathies. Immune complexes may form in the circulation and precipitate in
the kidney, or form in the kidney by binding of antibodies from the circulation
to antigens in the glomerular basement membrane. The localizations of immune
complex deposition in the various compartments of the glomeruli determine the
development of different forms of glomerulonephritis. Cellular immunological
reactions play a part in the development of tubulo-interstitial nephritis and
possibly also of minimal change nephropathy' and focal segmental
glomerulosclerosis. The role of cellular immunological reactions in the
development of most other nephropathies is less clear. Persistence of
nephropathies leads to glomerulosclerosis and renal interstitial fibrosis.
Ultimately, these cause loss of kidney function and necessitate haemodialysis.
PMID- 9646608
TI - [Immunosuppressive therapy for idiopathic membranous glomerulopathy].
AB - Idiopathic membranous nephropathy is the most frequent cause of nephrotic
syndrome in adults. The natural course of idiopathic membranous nephropathy is
characterized by a high incidence of spontaneous remissions. Some 50% of the
patients reach end-stage renal disease. Treatment with corticosteroids alone is
not efficacious; treatment with a combination of immunosuppressive drugs improves
renal survival. However, because of the high incidence of spontaneous remissions
and the risk of treatment-related toxicity, immunosuppressive treatment should be
reserved for patients with proven renal insufficiency. Cyclophosphamide appears
to be more efficacious and better tolerated than chlorambucil. Identification of
high-risk patients at an early stage of the renal disease may contribute to a
more efficient use of immunosuppressive treatment.
PMID- 9646609
TI - [Clinical thinking and decision making in practice. A patient with decreased
vision and a skin disorder].
AB - In a 48-year-old man who suffered from progressive loss of vision in his left eye
and metamorphopsia, pseudoxanthoma elasticum was diagnosed. Angioid streaks were
observed in both eyes and the skin showed small yellow papules in a linear
pattern. The right retina was twice treated by laser coagulation which resulted
in temporary regression of neovascularization. Pseudoxanthoma elasticum is a
genetic disorder with variable penetrance. There is no treatment. Patients should
be told to refrain from contact sports and to avoid using aspirin.
PMID- 9646610
TI - [Mammographic surveillance of breast cancer patient relatives; implementation of
guidelines formulated by the Netherlands College of General Practitioners].
AB - OBJECTIVE: To determine the implementation of the guidelines for mammographic
screening of breast cancer relatives formulated by the Dutch College of General
Practitioners (NHG), in daily practice. DESIGN: Prospective, descriptive.
SETTING: Kennemer Gasthuis, location EG, Haarlem, the Netherlands. METHODS: For
all asymptomatic women referred for mammography to our department of radiology by
their general practitioners between January 1, 1992 and August 1, 1995 because of
a family history of breast cancer, who had normal or benign radiological findings
and fulfilled the NHG criteria (aged 35 years or older with a first degree family
history of breast cancer), we advised a repeat mammogram within 1-2 years. After
2 years we checked in the hospital information system whether or not a patient
had undergone repeat mammography in the Kennemer Gasthuis; in case of non
reattendance at this hospital general practitioners were asked by questionnaire,
and if necessary by telephone, if follow-up mammography had been performed
elsewhere. RESULTS: Out of the 510 referred women, 405 (79.4%) met the NHG
criteria. In 370 the radiological findings were 'normal' or 'benign' and the
follow-up data were complete. Of these 370 women 201 (54.3%) underwent a repeat
mammogram within two years. This examination was performed more often if breast
cancer of a first degree relative had been diagnosed premenopausally (126/208 =
60.6%) rather than postmenopausally (75/162 = 46.3%; 95% confidence interval for
the difference: 3.6-25.0). CONCLUSION: General practitioners in 50% of the cases
complied with the recommendations for regular mammographic screening of breast
cancer relatives. Their compliance may be increased by introduction of simple
procedures into the computerized system for identification of risk factors and a
systematic planning of screening examinations.
PMID- 9646611
TI - [Recommended dietary allowance of folic acid is insufficient for optimal
homocysteine levels].
AB - OBJECTIVE: To determine the effect of short term supplementation of vitamin B6
(pyridoxine) followed by folic acid in apparently healthy volunteers on the
fasting plasma homocysteine concentrations (hyperhomocysteinaemia is an
independent risk factor for premature atherosclerosis). DESIGN: Prospective,
descriptive. SETTING: Academic Hospital Groningen, the Netherlands. METHODS:
Apparently healthy Dutch volunteers, aged 20-75 years, were supplemented with
vitamin B6 1 mg/kg/day during 7 days followed by folic acid 5 mg/day during
another 7 days. On days 0, 7 and 14 the fasting plasma homocysteine
concentrations were measured. A change of an individual's plasma homocysteine
level was considered statistically significant if the change in percentage
exceeded 2.8 times the sum of the analytical and the intraindividual biological
variation. RESULTS: There were 103 participants, 45 males and 58 females, with
average ages of 43 and 44 years, respectively (on day 7, data were available on
101 participants). Baseline folic acid concentrations of all participants were
above the lower limit of the reference range. Eight and two of them had vitamin
B6 and vitamin B12 concentrations below the reference range, respectively. Plasma
homocysteine was inversely related to plasma levels of folic acid and vitamin B12
at that moment. During vitamin B6 supplementation the mean plasma homocysteine
level did not change; one participant exhibited a significant plasma homocysteine
decrease. During folic acid supplementation the mean plasma homocysteine
decreased from 11.7 mumol/l (SD: 5.6) to 9.1 (SD: 3.4); 40 participants (40%)
exhibited significant plasma homocysteine decreases. At the end of the study
plasma homocysteine was still related to plasma vitamin B12. CONCLUSION: The
folic acid status of the participants at baseline was not associated with the
lowest plasma homocysteine levels. Since atherosclerosis risk may increase
continuously with increasing plasma homocysteine, it may be wise to keep plasma
homocysteine levels as low as possible. To reach this goal, the recommended
dietary allowance of folic acid may have to be increased.
PMID- 9646612
TI - [Primary peritonitis due to Streptococcus pneumoniae in childhood].
AB - Three patients, two boys of 5 months and 6 years and one girl aged 4 years,
presented with acute abdominal pain, vomiting and fever, suggesting peritonitis.
Imaging examinations (abdominal survey roentgenogram and (or) echography),
exploratory laparotomy (in two patients) and blood cultures with growth of
Streptococcus pneumoniae led to the diagnosis of primary peritonitis. Intravenous
antibiotics led to recovery, in one patient complicated by paralytic ileus, which
was treated surgically. Primary peritonitis is a rare condition which should be
considered in the differential diagnosis of children with an acute abdominal
syndrome. Conditions requiring surgery should be excluded by imaging examinations
or laparotomy. When the diagnosis is confirmed by paracentesis or laparotomy,
antibiotic treatment has to be started.
PMID- 9646613
TI - [Impressions on the thighs; semicircular lipoatrophy].
AB - An otherwise healthy woman aged 28 had symmetrical band-shaped dents on both
thighs. She worked as a secretary; several female colleagues showed identical
lesions. An investigation showed that the arrangement of the office equipment
combined with sharp-edged desk tops caused these abnormalities. The diagnosis
made read 'semicircular lipoatrophy caused by repetitive leaning against a desk'.
This is probably a common problem, although it rarely leads to consultation of a
dermatologist.
PMID- 9646614
TI - [The significance of publication in Dutch medical journals using an external peer
review system].
AB - Impact factors of the journals in which scientific work is published play an
important part in the assessment of scientific research. Impact factors are
determined by the number of citations in the international literature of articles
published in journals which are indexed by Current Contents (Science Citation
Index). Publications in Dutch scientific journals-not admitted to Current
Contents--such as Nederlands Tijdschrift voor Geneeskunde ('Dutch Medical
Journal')--score lower in the assessment of scientific research. At a conference
organized by Nederlands Tijdschrift voor Geneeskunde it was emphasized that there
should be more appreciation for the transfer of medical knowledge and experience
in the Dutch language. It is estimated that not more than about 10% of the Dutch
physicians read foreign medical journals. Publications in the Dutch language have
an important role in the teaching process and affect the quality of health care.
Scientific medical publications should not be judged only by the impact score
based on the Science Citation Index. There should be a second scoring system for
publications in Dutch medical journals using an external peer review system which
are not admitted to Current Contents.
PMID- 9646615
TI - [Visitation of medical schools in 1997].
AB - The visitation committee medicine and health studies in 1997 visited all eight
Dutch medical schools. A quality judgement was formed based on the results of a
self-analysis of these schools and extensive research on the spot. The conclusion
was that all schools inspected turn out physicians who can be trusted to do their
work well. However, the committee judges the curricula of some of the schools to
be very traditional: too much oriented towards the basic sciences with hardly any
room for contributions of the students themselves.
PMID- 9646616
TI - [Medical decisions made by teams: carefulness and responsibility].
AB - To a growing extent, medical decision making takes place in the context of a
team. Where multidisciplinary cooperation is necessary and the decisions to be
taken are complex and consequential (in particular at the beginning and the end
of life) joint decision making is considered an essential requirement of careful
medical practice. From a legal point of view, this raises the question who is
accountable for such decisions. Basically, accountability (and the liability that
may result from it) will stay with the individual participants, and in particular
with the first responsible, attending physician. In this respect, decision making
in such situations is not basically different from other, more informal
consultation structures (such as regular case reviews at department level) which
are current practice in many health care institutions. Finally, if joint decision
making is required, it should be clear in advance how decisions are to be arrived
at in the team.
PMID- 9646617
TI - [Inventory and follow-up of patients with surgery for (uterine) vaginal prolapse,
combined with or without, (masked) stress incontinence].
PMID- 9646618
TI - [Penicillin: just in time].
PMID- 9646619
TI - Vastatin trials: lessons from hypertension history.
PMID- 9646620
TI - Human volunteer studies in consumer product research.
PMID- 9646621
TI - Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in
comparison with simvastatin and pravastatin, in subjects with
hypercholesterolemia.
AB - BACKGROUND: High levels of total and LDL-cholesterol are associated with an
increased risk of atherosclerotic vascular disease. Lowering of serum cholesterol
levels by pharmacologic intervention with inhibitors of cholesterol synthesis,
the so-called statins, reduces the incidence of cardiovascular events in subjects
with and without atherosclerotic manifestations. In a 16-week, multicenter,
randomized, open-label cross-over study we compared the efficacy and safety of
the new compound atorvastatin for reducing LDL-cholesterol with simvastatin or
pravastatin. METHODS: Following a 4-week placebo-controlled baseline period
patients with LDL-cholesterol between 4.1 and 6.2 mmol/l and serum triglycerides
below 3.4 mmol/l were randomly assigned to treatment either with 5 or 20 mg
atorvastatin, or with 10 mg simvastatin or 20 mg pravastatin once daily for 4
weeks. After a placebo-washout period of 4-6 weeks, patients switched to the
alternate treatment. At the end of weeks 3 and 4 of each study phase the serum
concentrations of lipid parameters and apolipoproteins as well as safety
parameters were determined. RESULTS: A total of 78 subjects entered the study.
Treatment with 5 mg atorvastatin reduced total and LDL-cholesterol by 21 and 27%,
respectively, which was similar to 10 mg simvastatin (total cholesterol -20%, LDL
cholesterol -28%) and 20 mg pravastatin (-18 and -24%, respectively). The effects
of this low dose of atorvastatin on triglyceride levels (-16%) was not different
from that of simvastatin and pravastatin (-8 and -11%, respectively). Treatment
with 20 mg atorvastatin caused significantly larger reductions in total
cholesterol (-33%) and LDL-cholesterol (-44%), serum triglycerides (-23%), and
apo B (-40%) compared to simvastatin and pravastatin. Atorvastatin was well
tolerated, and no serious or medically important adverse events were observed.
CONCLUSIONS: We conclude that atorvastatin is a safe and very efficacious
cholesterol-lowering agent, which also possesses significant triglyceride
lowering properties.
PMID- 9646622
TI - Ethical review of human experimentation in the consumer products industry.
AB - BACKGROUND: Ethical review of human experimentation in the consumer products
industry is important and provides instructive parallels and contrasts with
clinical medical research. The procedures used in Unilever NV/plc are described.
METHODS: A central body sets standards for and monitors compliance with ethical
review of human studies throughout Unilever. Guidance has been produced on many
topics including issues applying generally to human experimentation and more
specifically to the consumer products sector. RESULTS: Deficiencies and
inconsistencies in the procedures for ethical review and the care of subjects
during the conduct of studies have been identified and corrected. Appropriate
uniform standards have been achieved across all Unilever operations. CONCLUSION:
All human experimentation in the industry needs adequate ethical review. Although
the methods used by individual companies may differ, procedures must ensure
uniform high standards across a global industry.
PMID- 9646623
TI - Ischaemic colitis and lung infiltrates caused by extramedullary haematopoiesis in
a patient with an acute erythroid leukaemia following polycythaemia vera.
AB - A patient with 'spent' polycythaemia vera showed extensive extramedullary
haematopoiesis (EMH) in non-haematopoietic tissue clinically resulting in an
ischaemic colitis and respiratory symptoms due to lung infiltrates. On laboratory
investigation, the EMH also included immature erythroblasts due to acute
erythroid leukaemia. It is hypothesised that the abnormal homing of erythroid
progenitors might be related to the abnormal expression of antigens, such as
CD36.
PMID- 9646624
TI - Onset of coeliac disease after a spontaneous miscarriage during a holiday in
Australia: coincidence or causal relationship?
AB - Diarrhoea contracted whilst travelling in a (sub)tropical country often has an
infectious cause. However, dietary changes can also be of importance. We describe
the case of a 28-year-old woman, who developed severe coeliac disease during a
trip in the Australian outback. The nutritional history revealed that the
patient's diet contained more wheat products during her trip than she was used to
in Holland. Moreover, the onset of symptoms coincided with a spontaneous
miscarriage of an 8-week-old embryo. This correlation has been described in
several case reports in the literature. However, the pathophysiologic mechanism
behind this correlation is unknown. Some speculative mechanisms are proposed
here. Further investigations into this relationship could increase our
understanding of the immunopathogenesis of coeliac disease.
PMID- 9646625
TI - Pneumomediastinum: an unusual complication of bronchial asthma in a young man.
AB - We report a patient with bronchial asthma who presented with pneumomediastinum,
pneumopericardium, pneumoretroperitoneum, pneumorrhachis and extensive
subcutaneous emphysema, after a period of coughing. Pathogenesis, diagnostic
procedures and treatment of pneumomediastinum and its complications are
discussed.
PMID- 9646626
TI - [Abuse of analgesics, headache, family practitioner and neurologist].
PMID- 9646627
TI - [Response to treatment of chronic daily headache with analgesic abuse].
AB - The overuse of analgesics in patients with chronic daily headache (CDH)
perpetuates and worsens the headache. The aim of this study was to evaluate the
clinical response to withdrawal of analgesics and to preventive treatment in a
group of patients with CDH. Eighty-four patients who were taking daily
symptomatic medications, and suffering from CDH were studied. Treatment consisted
of withdrawal of daily symptomatic medications and prophylactic therapy.
Improvement was considered when intensity and frequency of the headache were
reduced more than 50%. After a 2-15 months follow-up, 57 of the 76 patients that
continued in the study had improved. From these, 98% had reduced the consumption
of analgesics below the figures considered as abuse and a 94% took the
prophylactic medications correctly. After giving up the preventive treatment, 26%
of the patient presented CDH and the 60% overuse again of analgesics. These
results show that withdrawal of analgesics is necessary for improvement in
patients with CDH, but the possibility of relapses is elevated. We think that
there are other factors implicated in the development of CDH. We therefore
believe that in order to avoid the relapses this group of patients need follow-up
and preventive treatments during long periods of time.
PMID- 9646628
TI - [Genetics of mental retardation].
AB - Mentally retarded patients can be grouped in two categories: severe forms seen in
4 of every thousand live births and mild forms that occur approximately five
times more often. Approximately half of severe cases of mental retardation are
genetically determined, and half of these fall under the category of X-linked
mental retardation (XLMR) disease. The XLMR group is currently comprised of 105
highly varied types of retardation that can be associated with a fragile X
chromosome, biochemical defect, neurologic alterations, bony dysplasia and a
range of malformations. Along with such syndromes (which are specific), some 40
familial XLMR entities (nonspecific) can be identified in which mental
retardation is the only sign. Cytogenetic testing to identify dysmorphic
syndromes caused by chromosomal disease and molecular biology studies are
indispensable for identifying the genes responsible for XLMR syndromes. Healthy
carriers can also be found. It thus becomes possible to provide appropriate
genetic counseling for families and to achieve a prenatal diagnosis in some
cases.
PMID- 9646629
TI - [Current surgical treatment of Chiari type I malformation and Chiari I
syringomyelia complex].
AB - Chiari type I malformation and so-called Chiari-I/syringomyelia complex continue
to inspire controversy. Disagreement on these malformations concern both
etiopathogenesis and treatment. Our still poor understanding of the natural
course of the disease, the lack of consensus regarding therapeutic indications
and even disagreement on appropriate surgery all contribute to cause
disagreement. Significant progress has been made in our understanding of
contributing etiopathogenetic factors in recent years. The most widely accepted
hypothesis is that anomalous embryonic development characterized by paraxial
mesodermal insufficiency would put volumetric constraints on postnatal
development of the posterior fossa. We review historical and current
controversies regarding Chiari type I malformation and classic theories on
causative and contributing factors. We also discuss the latest surgical
treatments that have been suggested, as well as associated anomalies--mainly
syringomyelia, hydrocephalus and malformed cranial-cervical articulation.
Finally, we propose a protocol useful for the diagnosis and treatment of Chiari
type I malformation associated with dilation of the ventricular system.
PMID- 9646630
TI - [Cranial magnetic resonance of a 25-year-old woman with Norman's disease].
PMID- 9646631
TI - [Familial internal carotid dissection].
AB - Cervicocerebral arterial dissections is responsible for 20% of first strokes in
young adults. Several diseases of the connective tissue and wall vessels
anomalies are considered predisposing of arterial dissection. Familiar cases have
been reported in 5%, according to hereditary primary arteriopathy, such as
fibromuscular dysplasia. However, the nature of this arteriopathy has been rarely
proved. We present two sisters with spontaneous dissection of the internal
carotid artery with details suggestive of an atypical way of fibromuscular
dysplasia in one of them.
PMID- 9646632
TI - [Focal dystonia and tremor secondary to brain stem tuberculoma].
AB - Brainstem tuberculoma is exceptionally observed. We report a 44 year-old
immunocompetent man with proven diagnosis of miliary tuberculosis (TBC) who
developed a complex neurological syndrome characterized by right ophtalmoplegia,
left-sided hemiparesis and hemihypoesthesia and a gross ipsilateral postural and
action tremor with hand dystonia. A ponto-mesencephalic mass was detected by CT
and MRI studies of the brain. Clinical, bacteriological and neuroimaging studies
allowed to suspect a ponto-mesencephalic tuberculoma. Long-term therapy with anti
TBC drugs and steroids was started, achieving clinical and imaging improvement
which retrospectively confirmed the diagnosis. Although with less amplitude,
tremor persisted but a complete disappearance of focal dystonia was observed. The
pathogenesis of both abnormal movements is particularly discussed since hand
dystonia has never been mentioned in the literature as a consequence of brainstem
damage.
PMID- 9646633
TI - [Unilateral aplasia of the cerebellum in Aicardi's syndrome].
AB - A case of unilateral aplasia of the cerebellum in a girl with Aicardi's syndrome
is described. Aplasia of an entire hemisphere is one of the least frequent
malformations of the cerebellum. Hypoplasia, partial hemispheric defects of the
cerebellum and, rarely, complete absence of one hemisphere have been described in
Aicardi's syndrome, which is associated with multiple systemic and CNS
malformations. In our patient, who presented the characteristic trial of
infantile spasms, callosal agenesia and retinal lacuna, we also saw right
cerebellar aplasia along with other CNS malformations using magnetic resonance.
We discuss the possibility that this aplasia arises as the result of a
developmental defect of the posterior arterial system of Willis's polygon.
PMID- 9646634
TI - [Comment on the letter to the editor: "Acute hydrocephalus and cerebral abscess
in meningitis due to Listeria monocytogenes"].
PMID- 9646635
TI - [Who should treat stroke].
PMID- 9646636
TI - [Motor polyneuropathy due to massive ingestion of metronidazole].
PMID- 9646637
TI - [Paralysis of the hypoglossal nerve in the presentation of dural arteriovenous
fistula of the posterior fossa].
PMID- 9646638
TI - [Migraine with episodic unilateral mydriasis: parasympathetic dysfunction or
adrenergic hyperactivity?].
PMID- 9646639
TI - Overview of the current status of PET in breast cancer imaging.
AB - Present limitations of available procedures for the diagnosis of breast cancer
have stimulated the development of new methods based on Positron Emission
Tomography (PET). PET can be used to evaluate primary lesions, regionally
metastatic and systemic metastases of breast cancer by use of tracers including
15O-water 62Cu PTSM, [11C]L-methionine, [18F]fluordeoxyglucose and [18F]fluoro-17
estradiol, for the assessment of blood flow, metabolism and receptor density. FDG
PET is an excellent clinical method to detect primary breast lesions over 1 cm in
diameter and to characterize such lesions. Several reports have also indicated
various degrees of sensitivity and specificity of PET-FDG in detecting axillary
lymph nodes. However, the precise role of PET in staging breast cancer remains to
be defined in careful prospective studies. Prospective evaluation of PET during
breast cancer chemohormonotherapy demonstrated a decline in FDG uptake in
patients responsive to treatment, while no significant decline in FDG uptake is
seen in the non-responding patients examined post initiation of treatment. PET
may be useful when used in combination with other techniques of morphological
imaging, for the proper characterization of hypermetabolic tissue. Additional
studies including large populations with known or suspected breast cancer will
enhance the clinical role of this technique for solving difficult diagnostic
questions.
PMID- 9646640
TI - PET imaging of breast cancer with fluorine-18 radiolabeled estrogens and
progestins.
AB - Through the use of fluorine-18 radiolabeled estrogen receptor ligands and
Positron Emission Tomography (PET), imaging of estrogen receptor-positive (ER+)
breast lesions has been accomplished. Targeting the estrogen and progesterone
receptors found in receptor-positive breast cancer provides a means of diagnosing
the disease non-invasively. The structure-activity relationship of evaluated
fluorine-18 ligands are summarized and design considerations for construction of
novel target ligands discussed. The role of the serum protein sex hormone-binding
globulin (SHBG) in transport and metabolism of estrogens is related to target
tissue uptake. A historical review of fluorine-18 radiolabeled estrogens includes
the clinical study of 16 alpha-[18F]fluoroestradiol-17 beta (18FES) for imaging
ER+ breast lesions. The success of 18FES in the clinical setting has shown the
significance of PET in imaging primary and metastatic breast cancer by allowing
for assessment of tumor response to tamoxifen therapy after as little as 7 days
of treatment. Advantages of visualizing the tumor through targeting the
progesterone receptor (PR) include PET imaging to follow the progress of
tamoxifen therapy while the estrogen receptors are blocked. Clinical studies with
the PR ligand 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (18FENP) were not
successful due to high hepatic uptake and poor correlation of tumor uptake with
receptor content. Second generation PR ligands with decreased non-specific
binding are predicted to be effective imaging agents for human PR+ breast cancer
from studies in the immature rat and are ready for clinical evaluation.
PMID- 9646641
TI - Somatostatin receptors and breast cancer.
AB - The study of breast carcinogenesis is complicated by the heterogeneity of the
disease. One way of simplifying is to subdivide these tumors into clinically
relevant subgroups. There are indications that breast carcinomas, of which some
express the somatostatin receptor (SS-R), can be divided this way. Expression of
somatostatin receptors (SS-R's) in human primary breast cancer has a very high
incidence. This can be demonstrated by in vitro autoradiography and in vivo by
somatostatin receptor scintigraphy. However the clinical significance of
somatostatin receptor expression in human breast cancer needs to be investigated.
In this review article we summarize the current understanding of the functional
role of somatostatin receptors in human breast cancer. Their relationship with
neuroendocrine differentiation of the cancers and genetic and patient
characteristics, the role of in vivo SS-R's visualization, and the possible
medical and radiotherapeutic implications of these findings are discussed.
PMID- 9646642
TI - Estrogen receptor scintigraphy.
AB - Radio-labeled estrogen receptor ligands are tracers that can be used for
functional receptor diagnosis. Their specificity towards receptors, together with
the fact that only 50-70% of mammary carcinomas are receptor positive, renders
them unsuitable for detection of primary tumors or metastases, and this means
that estrogen receptor scintigraphy can be used neither for tumor screening nor
for staging. However, both 18F-labeled and 123I-labeled estradiol derivatives are
suitable for in vivo imaging of estrogen receptors. Their high specificity,
established in animal experiments and in vitro studies has been reproduced in in
vivo applications in humans. Tracers with positron radiation emitters are,
however, hardly suitable for broad application owing to the short half-life of
18F, which would mean that users would need to be situated close to a cyclotron
and a correspondingly equipped radiochemical laboratory. The number of available
PET scanners, on the other hand, has increased over the last few years,
especially in Germany, so that this, at least, does not present a limiting
factor. All the same, 123I-labeled estradiol derivatives will find more
widespread application, since the number of gamma-cameras incorporating modern
multi-head systems is several times greater. The results of studies with 123I-E2
scintigraphy published to date are very promising, even given the initial
technical problems mentioned above. As a method of examination, it could be
optimised by using improved tracers with a higher tumor contrast and less
disturbance from overlapping in diagnostically relevant locations, for instance,
by selecting tracers with higher activities whose excretion is more renal than
hepatobiliary. The use of modern multi-head camera systems can also be expected
to improve the photon yield.
PMID- 9646643
TI - Radioimmunolocalization of primary and metastatic breast cancer.
AB - The appropriate therapy for breast cancer depends mainly upon early and reliable
tumor detection, correct tumor staging and accurate re-staging after therapy.
Current radiological imaging methods are based primarily on morphology resulting
in high sensitivity but lacking specificity. Established nuclear medicine
techniques are sensitive but not very specific. To improve specificity, a number
of monoclonal antibodies, selected against a particular tumor-associated antigen
expressed on the surface of breast cancer cells, have been radiolabeled for
imaging in vivo tumor localizations. In theory, radioimmunodetection offers the
potential to demonstrate cancer cells even in subradiological disease, or when
anatomy-based imaging methods may be unable to distinguish the nature of an
evident mass, making the differential diagnosis between an inflammatory reaction,
a postsurgical fibrosis, or a truly viable tumor impossible. Suspected tumor
recurrence indicated by increasing tumor marker levels could be another clinical
indication for radioimmunolocalization, even if standard imaging modalities are
negative. A large number of antibodies against different epitopes of human
neoplastic breast tissue have been investigated previously. However, a highly
specific and sensitive monoclonal antibody for immunoscintigraphy and
radioimmunotherapy has not yet been found. This review addresses tumor-biological
considerations, radioisotopes and radiolabeling methods, tumor targets and
different monoclonal antibodies used for immunoscintigraphy (incl. SPECT amd PET)
of breast cancer.
PMID- 9646644
TI - Skeletal scintigraphy in breast cancer management.
AB - Since its introduction in 1971 bone scintigraphy has become the classical
procedure to confirm or exclude metastatic spread of breast cancer to skeleton.
Recent developments in tomographic imaging (CT, MRI) as well as a more critical
attitude towards technical diagnostic tests have raised the question about the
present role of scintigraphy in staging and follow-up of breast cancer patients.
Based upon systematic retrospective analyses bone scintigraphy is recommended for
the initial staging of high risk patients (node-positive). In the follow-up of
symptom-free patients bone scintigraphy did not prove to be necessary while it
should be used in symptomatic patients to confirm and demonstrate the extent of
metastatic disease. The bone scan is also useful for treatment control. However,
due to similar findings in case of response (flare phenomenon) as well as tumor
progression clinical relevance appears to be limited. In future increasing
competition with CT and/or MRI will probably occur. Since MRI was proven to be
more sensitive as well as specific in direct comparison, all efforts should be
made to improve image quality and to reduce costs of skeletal scintigraphy. PET
using F-18 fluoride might be an interesting alternative, if it becomes available
for reasonable prices.
PMID- 9646645
TI - Optimized sentinel node scintigraphy in breast cancer.
AB - INTRODUCTION: Axillary lymph node dissection (ALND) represents an important
staging procedure in the surgical treatment of breast cancer. However, it may
result necessary in tumors of little dimensions because of low percentage of
metastatic axillary lymph node (ALN). If a non invasive technique predicted the
status of ALN, ALND procedures could be avoided. We carried out this study i) to
establish the best technique to perform the lymphoscintigraphy for detecting the
sentinel node in breast cancer and ii) to determine whether a clear sentinel node
reliably predicts a disease free axilla. METHODS: 215 patients were submitted to
the lymphoscintigraphy before surgery. Three different colloidal radiotracers
with particle size ranging between < 50 and 1000 nm were injected sudermically or
peritumorally. Early and late images were recorded in anterior and oblique
projections and the SN was marked on the skin and biopsied using a gamma
detection probe (GDP) during surgery. RESULTS: The SN was identified in 210/215
cases (97.6%). The SN accurately predicted axillary ALN status in 204/210 (97.1%)
patients in whom a sentinel node was identified and in all the cases (45
patients) with tumor < 1.5 cm in diameter. In 38/101 cases with metastatic
axillary nodes (37.7%) the only positive node was the SN. CONCLUSIONS:
Lymphoscintigraphy can easily locate the SN in breast cancer. SN detection
resulted easier when large size microcolloids were used. Subdermally
administration appeared the best way of injection for palpable lesions. Breast
cancer patients without clinical involvement of the axilla should undergo SN
biopsy routinely and this may allow sparing complete axillary dissection when the
SN is free of disease.
PMID- 9646646
TI - Nuclear medicine approaches for detection of axillary lymph node metastases.
AB - In breast cancer patients the detection of axillary lymph node involvement is a
very critical issue, in view of the earlier diagnosis of the disease in recent
years, and the increased frequency of very small tumors at first presentation.
The size of cancer is related to the risk of axillary metastases, and this may
affect the prognosis and the therapeutic strategies. Axillary lymph node
involvement is generally recognized as an index of distant microdiffusion, and as
it affects overall and disease-free survival, represents the basis for adoption
of adjuvant chemotherapy. Routine axillary lymph node dissection (ALND) is
expensive, and does not benefit about 70% of early breast cancer patients which
are node negative (pN-). Today most of these patients have to sustain the
potential morbidity and the economic costs of ALND. The clinical approach is
known to be an unreliable diagnostic tool, and for the detection of axillary
metastases, conventional X-ray techniques are also unable to solve the problem.
By contrast, nuclear medicine procedures have revealed a very interesting
diagnostic potential in recent years. This paper analyzes the numerous studies
conducted in the field of lymph node visualization and the heterogeneity of the
published experiences, taking into account the different approaches proposed in
the literature: a) imaging with gamma-emitting tumor seeking agents; b)
radioimmunoscintigraphy intravenous (i.v.) or by the interstitial route; c)
lymphoscintigraphy with colloids and gamma probe sentinel biopsy; d) positron
emission tomography (PET). Although it is very difficult to make a definitive
statement about the clinical efficacy of all these methods, this paper reports
the most important series of patients examined in the literature as well as the
author's own experiences. This can serve as the basis for a better understanding
of the potential of nuclear medicine procedures, and gives the reader the
opportunity to weigh advantages and drawbacks of each method. At present,
lymphoscintigraphy with gamma probe sentinel biopsy and FDG-PET are the nuclear
medicine approaches with the best diagnostic performance. However, a correct
comparison of the methods will not be possible, until their careful assessment in
the same patients is performed. In addition, a final statement today should
consider also the increasing need to carry out an economic analysis by evaluating
the cost-effectiveness of the examinations.
PMID- 9646647
TI - Impact of the diagnostic methods on the therapeutic strategies.
AB - Over the last 25 years the diagnostic approaches and therapeutic strategies of
breast cancer have dramatically changed. The relationship between diagnosis and
therapy has gradually become more complex due to the ever more sophisticated
diagnostic tools (mammographic screening, digital mammography, magnetic
resonance, SPECT scan and FDG-PET), which have improved resolution limits and
accuracy, and also due to the different therapeutic planning applied to breast
cancer in these years (conservative surgery, neo-adjuvant chemotherapy, axillary
dissection or not). Thus, in this paper, we have briefly analyzed the many open
questions in breast cancer management and the clinical challenges of present
diagnostic tools in relation to pre-, peri- and postoperative phases, and to
therapeutic strategies in general. The main goal of mammographic screening is to
detect early invasive cancers and to treat them at the first useful moment.
However, at which age should one begin screening, and what is the impact on
overall survival, the cost-effectiveness, and, most of all, the best operative
approach to suspect lesions? Can digital mammography give a better quality of
imaging with respect to conventional mammography? Does unexpected multicentricity
and/or multifocality, which is sometimes showed by magnetic resonance, have any
clinical relevance? Is this technique really better than traditional methods for
the identification of local recurrence? Is scintimammography able to improve the
low diagnostic accuracy of mammography on non-palpable breast lesions? Moreover,
at present, the need for axillary dissection and its therapeutic and staging
value is deeply debated: however, clinical detection of axillary metastases is
not a reliable diagnostic tool and there are no conventional radiologic
techniques to be used: recently nuclear medicine imaging has provided various
approaches, such as SPECT scan with different tracers, FDG-PET, or
lymphoscintigraphy with gamma probe sentinel biopsy: there are not only
methodologic but also phylosophic differences in using these techniques. Neo
adjuvant chemotherapy has allowed a dramatic reduction of primary breast cancer
with a replanning of the surgical approach to large breast tumours but, at the
same time, has posed new questions such as the adequacy of diagnostic pre- and
perioperative revaluation. Finally, does postoperative follow-up take advantage
of intensive diagnostic programs and are there therapeutic margins which would
improve survival of patients with metastatic disease? This paper is an attempt to
analyze the answers given in the literature. Nevertheless, at present, this
matter is globally in progress and a scientific debate will provide, in the near
future, a new promising scenario for breast cancer management.
PMID- 9646648
TI - Neurogenesis in septum, amygdala and hippocampus in the marsupial brushtailed
possum (Trichosurus vulpecula).
AB - The times of origin of neurons in the septum, amygdala and hippocampus of the
marsupial brushtailed possum, Trichosurus vulpecula, were determined with 3H
thymidine autoradiography. The long time period for neurogenesis in the
brushtailed possum facilitated analysis of neurogenetic gradients in the brain. A
series of 20 possums were injected with 3H thymidine from postnatal (P) days 5-95
and were allowed to survive until brain cytoarchitecture was mature. Our results
indicate that septal neurogenesis was complete by P21 (38 days after conception)
with a medial to lateral gradient of neurogenesis evident in the lateral septal
division. Neurogenesis in the amygdala was complete in the basal, central and
medial amygdaloid nuclei by P21, and in the lateral amygdaloid nucleus by P46,
with a medial to lateral gradient of neurogenesis evident in basal, central and
lateral amygdaloid nuclei. In the hippocampus, neurogenesis of pyramidal cells
was complete in field CA3 by P50, and in field CA1 by P55. Early forming
pyramidal cells (P5-12) were distributed adjacent to the stratum oriens in fields
CA1 and CA3, with later forming pyramidal cells distributing in the middle of the
stratum pyramidale (P21-32) and on the edge adjacent to the stratum radiatum
(P46). Neurogenesis of dentate granule cells extended over a long period of time,
from P5, at least until P82, with the earliest forming granule cells (P5-12)
distributed adjacent to the stratum moleculare, and the latest forming granule
cells (P82) adjacent to the hilus.
PMID- 9646649
TI - [Peculiarities of pediatric anesthesia: premedication and inhalation induction].
PMID- 9646650
TI - [Nasal ketamine compared with nasal midazolam in premedication in pediatrics].
AB - OBJECTIVE: To compare the efficacy and side effects of midazolam and ketamine
administered nasally for pediatric premedication. PATIENTS AND METHODS: In this
double blind trial 60 children scheduled for elective surgery were randomly
assigned to two groups to receive 0.25 mg.kg or 5 mg.kg nasal ketamine. We
measured level of acceptance of medication, sedation, hemodynamic variables,
reaction to separation from parents, side effects and time until recovery from
anesthesia. RESULTS: The two groups were homogeneous. Acceptance of medication
was good or adequate in all patients. The level of sedation was significant in
both groups 10 min after premedication. Systolic arterial pressure was higher in
the ketamine group 20 min after administration of the drug and upon arrival in
the operating theater. Reaction to separation from parents was good in all
groups. Secretions were higher in the ketamine group and hallucinations were
experienced by three patients in the ketamine group and by two in the midazolam
group. We found no difference in time until spontaneous eye opening after
surgery. No complications were observed. CONCLUSIONS: The nasal route is
adequately accepted by children. Both drugs are effective by this route and
sedation is rapid. Time until postanesthetic recovery is similar with both drugs.
The doses used have wide safety margins.
PMID- 9646651
TI - [Comparative study of sevoflurane and nitrous oxide versus halothane and nitrous
oxide in pediatric anesthesia: efficacy and hemodynamic characteristics during
induction].
AB - OBJECTIVES: To study the efficacy, side effects and hemodynamics of anesthetic
induction in pediatric patients using sevoflurane and nitrous oxide or halothane
and nitrous oxide. PATIENTS AND METHODS: We studied 80 pediatric ASA I-II
patients aged between 1 and 10 years old scheduled for infraumbilical surgery of
short duration. The patients were randomly assigned to two groups of 40 to
receive one of the two drug combinations. All the children were premedicated with
nasal midazolam 0.2 mg.kg-1. Induction was by inhalation of increasing
concentrations of sevoflurane or halothane. The maximum inspired concentration
during induction was 7% for sevoflurane and 3% for halothane. We analyzed
induction time, side effects and hemodynamic variables. RESULTS: The induction
time was 2.06 +/- 0.5 min for halothane and 1.6 +/- 0.6 min for sevoflurane (p <
0.01). We observed no differences between the groups in coughing, laryngospasm,
bronchospasm, secretions, apnea, nausea, vomiting, agitation or hiccoughing.
Supraventricular beats appeared in 22.5% of patients in the halothane group and
in 5% of the sevoflurane group. Induction with both anesthetics caused
significant decreases from baseline blood pressure levels but no significant
changes in heart rate. CONCLUSIONS: Inhaled sevoflurane in 60% nitrous oxide
provides rapid but gentle anesthetic induction, with hemodynamic stability and a
low incidence of airway complications. Sevoflurane is therefore a reasonable
alternative to halothane for pediatric surgery.
PMID- 9646652
TI - [Preoperative information and informed consent in surgically treated patients].
AB - OBJECTIVE: Providing information is an important part of the doctor-patient
relationship. In hospital practice today, patients and/or their families are
sometimes given seriously inadequate information. Our aim was to analyze the
quality of information received by patients before anesthesia and surgery.
PATIENTS AND METHODS: The opinion of 300 patients (141 men and 159 women) at
Hospital Universitario "Virgen de la Arrixaca" (Murcia, Spain) was studied from
1993 to 1995. The sample was a stratified random one with sex and age as the
classifying variables. Surgery was scheduled in 150 cases and emergency in 150.
Mean age was 42.88 +/- 1.20 years (SD = 20.84; range 3-90 years). RESULTS:
Patients were unfamiliar with risks of surgery and anesthesia in 19% and 18.3% of
the cases, respectively. No information was received by 69.3% of patients
regarding surgical risks and an even higher 75% of patients received no
information on risks of anesthesia. In 3.6% of scheduled operations, neither
patient nor family members were required to sign a consent from, though these
cases involved patients under 18 years of age. For emergency surgery this
percentage was 5.4%. Lack-of-information percentages are higher in operations
requiring local or regional anesthesia. CONCLUSIONS: We must underline the poor
quality of patient knowledge about medical procedures and the scarce information
provided. Even fewer patients known about the risks of anesthesia. A patient's
signing of an informed consent form does not correspond to real knowledge of the
risks involved in the procedure.
PMID- 9646653
TI - [Relationship between mixed venous saturation and cardiac index, hemoglobin and
oxygen consumption in aortic surgery].
AB - OBJECTIVE: Mixed venous oxygen saturation (SvO2) depends mainly on four
variables: cardiac index (CI), hemoglobin concentration (Hb), arterial oxygen
saturation (SpO2) and oxygen consumption (VO2). Our aim was to study the
correlation between each of these variables and SvO2 during abdominal aortic
surgery, a situation which is of special interest because of associated
hemodynamic and metabolic variations and the high risk of cardiovascular events.
PATIENTS AND METHODS: Twelve patients undergoing intrarenal aortic surgery were
monitored by pulmonary artery catheter (Opticath), pulse oximetry and indirect
calorimetry (Deltatrac Metabolic Monitor). SvO2, CI (measured by thermodilution),
SpO2 and VO2 at six moments: post-induction (baseline), 1 min before and 1 min
after clamping (pre-C, post-C), 1 min (post-D) and 10 min after declamping and at
the end of the surgery. Hemoglobin concentration was measured at all moments
except 10 min after declamping. RESULTS: All variables except SpO2 varied
significantly (p < 0.001) during the study. SvO2 was associated with CI at all
moments except post-D and at the end of surgery. Hemoglobin concentration was
related to SvO2 at baseline and post-C. We found no correlation between SvO2 and
VO2 or SpO2 at any moment. CONCLUSION: Monitoring SvO2 in patients undergoing
aortic surgery is useful for detecting potentially prejudicial variations in
cardiac output or hemoglobin concentration.
PMID- 9646654
TI - [Anatomic basis of continuous axillary block of the brachial plexus with thoracic
reservoir].
AB - Although continuous axillary block is effective for periods of up to four to six
weeks, pain clinic patients with severe chronic pain in the upper extremities,
mainly resulting from neuropathic disease, can require continuous drug delivery
by catheter-reservoir for up to three months or longer. We studied possible
locations for implanting reservoirs or catheters from the perivascular axillary
space in fresh cadavers, checking for possible vascular or nerve damage after
applying the usual technique for reservoir implantation. The ideal location for
the reservoir is the subcutaneous tissue of the homolateral infraclavicular space
of the anterior side of the thorax. The customary procedures for inserting the
catheter along the subcutaneous route that extends from the perivascular axillary
space to the reservoir carry no risk of damaging vascular or nerve structures.
PMID- 9646655
TI - [Thoracic epidural analgesia in the postoperative period of pediatric surgery for
the repair of pectus excavatum and pectus carinatum].
AB - To assess thoracic analgesia by continuous infusion in surgery to repair pectus
excavatum and carinatum in children. This prospective study enrolled 14 children
aged 6 to 14 years old scheduled for surgery to correct pectus excavatum and
carinatum. After induction of general anesthesia, the T8-T9 epidural space was
accessed and a catheter was inserted to T3-T7 with radioscopic monitoring. A
loading dose of 0.03-0.04 ml/kg per segment to be blocked (5 segments: T3-T8) of
0.125% bupivacaine and 3 micrograms/ml fentanyl was given to children under 7
years of age; a dose of 0.02-0.03 ml/kg per segment was administered to children
over the age of 7 years. A continuous perfusion of 0.1-0.4 ml/kg/h was
maintained, with the possibility of additional boluses of 1 ml at 20 min
intervals during surgery and the first three days thereafter. An intraoperative
bolus was given when the level of blockade was not reached or when mean blood
pressure and heart rate increased 15% over baseline. Pain relief was assessed on
a numerical scale of 0 to 5 or on a scale of facial icons, depending on the
patient's age. During the postoperative period, the pediatric ICU nurse
administered a bolus if pain was [symbol see text]3 or heart rate increased 75%
over age-based reference values. Top-up analgesia was provided with Metamizole at
a dose of 25 mg/kg. No complications attributable to the technique or to
sympathetic blockade were observed. All tubes were removed in the operating room.
The thoracic epidural catheter was left in place for 70.3 +/- 2.6 h. Mean initial
doses of analgesia were 0.45 microgram/kg of fentanyl and 0.2 mg/kg of
bupivacaine. The mean number of complementary boluses was 3 +/- 1 during surgery,
5 +/- 2 on the first postoperative day and 4 +/- 1 on the second day. No patient
required top-up analgesia on the third day. Hemodynamic stability during surgery
and the postoperative period was good. Analgesia was excellent (< 2) for 78.5% of
the patients on the first day after surgery, for 85.7% on the second day and for
all patients on the third day. We recorded one case of pruritus (7.1%), three of
nausea (21.4%) that subsided when butorphanol was given epidurally (20
micrograms/kg), and two cases of light sedation. Thoracic epidural analgesia is
effective for alleviating postoperative pain from corrective thoracic surgery in
children. Side effects were minimal and no anesthetic complications were
observed.
PMID- 9646656
TI - [Epidural abscess secondary to the implantation of a thoracic catheter].
AB - Spinal compression related to the formation of an epidural abscess after epidural
blockade is a rare but serious complication. We report the case of a male patient
in whom a thoracic epidural catheter was implanted to provide analgesia after
trauma involving fracture ribs. The patient developed an epidural abscess within
one week of implantation. Delay in diagnosis led to persistent neurogenic bladder
symptoms in spite of aggressive treatment. We review causal factors, mechanisms
of formation, pathogenesis, diagnosis and management, as well as possible
relation between injury and abscess formation. We also emphasize the importance
of adequate vigilance as well as rapid diagnosis and adoption of therapeutic
measures in order to avoid permanent sequelae such as paresis, sensory deficits
or mechanical sphincter dysfunction.
PMID- 9646657
TI - [Esophageal perforation caused by barotrauma].
PMID- 9646658
TI - [Accidental overdose of caudal morphine chloride].
PMID- 9646659
TI - [Thoracic epidural anesthesia for radical mastectomy in a female patient with
multiple disorders].
PMID- 9646660
TI - [Pneumothorax during laparoscopic Nissen fundoplication].
PMID- 9646661
TI - [Blockade of the popliteal space. Response of the authors].
PMID- 9646662
TI - [Effect of mivacurium in patients chronically treated with anticonvulsant
agents].
PMID- 9646663
TI - [Surveys as scientific instruments].
PMID- 9646664
TI - [Analysis of the current status of neuroanesthesia in Spain using a national
survey].
AB - OBJECTIVES: Advances in complementary diagnostic explorations, surgical support
technology and the complexity of neurophysiological monitoring require
anesthesiologists to acquire specific knowledge for dealing with neurosurgery. We
aimed to study the implantation of new anesthetic-surgical techniques in the
field of neurosurgery, and the state of neuroanesthesia as a subspecialty in
Spain. MATERIAL AND METHODS: A 20-item postal questionnaire sent to
anesthesiology department heads of Spanish hospitals with neurosurgery teams.
RESULTS: We received responses from 62% of the hospitals surveyed. Of these, 69%
performed stereotaxic surgery, 30% functional cerebral surgery (for Parkinson's
disease and epilepsy) and 21% offered neuroendoscopy. In 38% of the hospitals
cerebral metabolism was monitored (hemoglobin oxygen saturation in the jugular or
regional cerebral oxygen saturation) and/or cerebral electrophysiology
(electroencephalogram, evoked potentials) and in 23.8% flows and pressures were
measured (transcranial precordial and/or tracheoesophageal Doppler).
Anesthesiologists specializing in neurosurgery are present in 62% of the
hospitals. Interventionist neuroradiology is performed in 57%. It was noteworthy
that 14.3% do not regularly have an anesthesiologist present during such high
risk procedures. CONCLUSIONS: Although most centers continue performing
"classical" neurosurgery with standard monitoring, a substantial proportion of
hospitals (38%) show evidence of advancing in anesthetic techniques for
neurosurgery in Spain. Anesthesia for neurosurgery as a subspecialty is available
in 62% of the responding hospitals.
PMID- 9646665
TI - [Satisfaction with locoregional anesthesia in women who had undergone cesarean
section].
AB - OBJECTIVES: To compare satisfaction with local-regional and general anesthesia in
women undergoing cesarean, the possible influence of time of evaluation and
recall of the anesthesiologist. PATIENTS AND METHODS: Retrospective study
performed in all women who delivered by cesarean in the 6 first months of 1997.
The women were assigned to two groups according to type of anesthesia, local
regional or general. Their satisfaction with anesthesia was evaluated by
questionnaire 48 to 72 hours after surgery and two weeks after release. Most
items required discrete-point answers, including a satisfaction of a scale of 0
to 10. During the second interview we also evaluated satisfaction with the
procedure and hospital in general, as well as recall of the anesthesiologist.
Group homogeneity was based on demographic, sociocultural, obstetric and surgical
variables. RESULTS: In a context of high satisfaction with anesthesia, 189 (76%)
of the 247 women receiving local-regional anesthesia gave high evaluations to the
anesthesia (8.90 +/- 1.5; mean: 10), compared with 58 (24%) of those receiving
general anesthesia (8 +/- 2; mean 8.5) (p = 0.001). Both groups were homogeneous
except for the distribution of emergencies, which occurred more often in those
receiving general anesthesia (p < 0.001). Women who had received local-regional
anesthesia expressed greater willingness to repeat or recommend the technique (p
< 0.001). The highest score in this group was from women receiving intradural
anesthesia along with fentanyl for local anesthesia, with significant differences
only in comparison to epidural anesthesia. The differences in responses between
the first and second interview were scarce. The hospital received a lower
evaluation than did either anesthesia or surgery (p < 0.001). The
anesthesiologist, who was less well recognized than the obstetrician was
remembered better among women receiving local-regional anesthesia (p = 0.008).
CONCLUSIONS: Local-regional anesthesia can improve levels of satisfaction over
that of general anesthesia among women undergoing cesarean surgery, and
contributes to maintaining recall of the anesthesiologist. These results may be
related to the fact of being conscious during the birth of a child.
PMID- 9646666
TI - [Indices of prediction of neurologic focality during carotid endarterectomy
carried out under regional anesthesia].
AB - OBJECTIVES: To examine the relations between the development of neurologic events
and the following variables: degree of stenosis of the contralateral carotid
artery, prior neurologic symptoms and stump pressure of the ipsilateral internal
carotid artery in patients undergoing carotid endarterectomy under regional
anesthesia. PATIENTS AND METHODS: We undertook a prospective study of 92 patients
undergoing carotid endarterectomy with a blockade of the superficial and deep
cervical plexus. Neurological integrity was assessed and internal carotid artery
stump pressure was monitored. Contralateral carotid artery stenosis and
neurologic disease present before surgery were studied. RESULTS: Neurologic
events developed when the carotid artery was clamped in 9.7% of patients. Mean
stump pressure was significantly lower in symptomatic patients (43 +/- 11 mmHg)
than in asymptomatic patients (74.6 +/- 24 mmHg) (p < 0.001). Neurologic symptoms
developed during clamping of the carotid in 27.2% of the patients with stump
pressure less than or equal to 50 mmHg, but in only 4.2% of those with stump
pressure surpassing 50 mmHg. Stump pressure was significantly lower in patients
with contralateral carotid stenosis. The incidence of neurologic events during
clamping was unrelated to contralateral carotid condition, however. Likewise,
neurologic symptoms before surgery was also unrelated. In six of the nine
patients with neurologic events, internal carotid stump pressure was less than or
equal to 50 mmHg, indicating that the sensitivity of this parameter to the
development of neurologic events in our series was 66%. CONCLUSIONS: Although
internal carotid artery stump pressure identifies a subset of patients likely to
have a higher incidence of neurologic events during carotid artery clamping, it
can not be considered the only criterion for placement of an intraluminal shunt
to prevent such events. The state of the contralateral carotid artery and
preexisting neurologic symptoms are not objective screening criteria for
identifying patients at high risk of neurologic events during carotid clamping.
PMID- 9646667
TI - [Comparative study of recovery times and psychomotor function after anesthesia
with desflurane or isoflurane].
AB - OBJECTIVE: To compare recovery from anesthesia with desflurane and isoflurane by
analyzing awakening and psychomotor function. PATIENTS AND METHODS: In this
prospective study of 30 ASA I-II patients undergoing general or urologic surgery
the following variables were assessed before surgery: confusion, fatigue,
drowsiness, torpor and pain. The Steward and Trieger tests of psychomotor
function were also applied. After induction and intubation, maintenance was with
isoflurane (0.6 +/- 0.3%) or desflurane (3 +/- 1.5%) and 60% nitrous oxide with
fresh gas at a rate of 1 l/min. After withdrawing the halogen and switching to an
open circuit (10 l/min), we counted time until appearance of the first sign of
awakening. Clinical variables and psychomotor function were assessed 5, 30, 60
and 90 min later. RESULTS: The two groups were similar anthropometrically.
Duration of anesthesia and surgery were also similar. Times until awakening, eye
opening, extubation and orientation were shorter in the desflurane group. Scores
for fatigue (5 min), confusion (5 and 30 min), motor incoordination (5 min) and
drowsiness (5 and 30 min) were also more favorable in the desflurane group.
Patients receiving desflurane also scored significantly better on the Trieger
test at 30 and 60 min. CONCLUSIONS: Recovery times are shorter with desflurane
than with isoflurane. Clinical variables are also more favorable with desflurane
and psychomotor function returns more quickly during the first hour after
anesthesia.
PMID- 9646668
TI - [Urapidil in anesthesiology: pharmacology and indications].
AB - This review aims to describe the pharmacological bases for using urapidil, a
recently introduced hipotensor, and to survey the literature on its therapeutic
possibilities. The anesthesiologist often sees hypertension during surgery and
must apply hypotensive treatment to prevent complications. Urapidil works mainly
by antagonizing postsynaptic alpha-1-adrenergic receptors and stimulating 5-HT1A
receptors, a double mechanism that provides vasodilation with moderate decrease
in blood pressure without reflex tachycardia. Adverse side effects are rare and
clinically unimportant. Onset is rapid after intravenous administration and
duration of action is short; dose can be easily adjusted based on response and
patient requirements. While urapidil has been used successfully in a variety of
diseases and surgical procedures, its pharmacological characteristics make it
particularly useful in patients at high cardiovascular risk or undergoing
neurosurgery, in which results are good. Although the oral form is not sold in
Spain, it is used in other countries to treat chronic high blood pressure.
Urapidil is a hypotensor with a wide range of indications (critical hypertension,
prophylaxis for hypertensive peaks and treatment of hypertension during surgery)
and few side effects.
PMID- 9646669
TI - [Cortical blindess as symptom of pre-eclampsia].
AB - Neurological complications during preeclampsia are not infrequent; the appearance
of total blindness is rare, however. We report the case of a 32-year-old
primipara with no outstanding history, who presented total loss of vision with no
accompanying neurological symptoms during week 37 of the pregnancy. Effective
early management of blood pressure to levels at which self-regulation of cerebral
perfusion could be established allowed total recovery of vision 8 hours after
admission to the intensive care recovery ward. Cranial computerized axial
tomography (CAT) showed bilateral occipital subcortical edema that resolved after
8 days. The patient was released 13 days after admission with no sequelae.
PMID- 9646670
TI - [Pulmonary edema of neurogenic origin and transtentorial hernia during anesthesia
induction in a child with ventriculoperitoneal shunt].
AB - We report the case of a 12-year-old boy with a peritoneal ventricular shunt who
developed acute pulmonary edema of neurogenic origin after laryngoscopy and
orotracheal intubation. Such maneuvers in the presence of diminished intracranial
distensibility caused transtentorial herniation. Delayed diagnosis led to death
in spite of appropriate treatment of postoperative complications.
PMID- 9646671
TI - [Anesthesia techniques in epidermolysis bullosa].
AB - Epidermolysis bullosa encompasses a group of rare clinical profiles marked by the
formation of bullae on the skin and mucosa as the result of slight mechanical
trauma. The anesthesiologist must take certain safety measures to monitor the
airway and must expect difficult venous access in patients with this disease. We
report our experience in providing anesthesia by various techniques for plastic
and maxillofacial surgery. Most anesthetic techniques can be considered safe if
they are performed with care and attention to detail.
PMID- 9646672
TI - [Anesthesiology journals in Internet].
PMID- 9646673
TI - [Reduction of gas leaks from laryngeal masks with controlled ventilation].
PMID- 9646674
TI - [A new case of acute pulmonary edema secondary to phenylephrine administered on
the conjunctiva in cataract surgery].
PMID- 9646675
TI - [Short-length subarachnoid anesthesia: which local anesthetic should be used?].
PMID- 9646676
TI - Morphometric comparison of the density of the mesangial deposits in idiopathic
IgA-nephropathy and Schoenlein-Henoch nephritis. An ultrastructural study.
AB - The present investigations performed by means of image analysis system was
undertaken to compare the electron-microscopic density of the mesangial deposits
in IgA nephropathy (IgAN) and Shoenlein-Henoch nephritis (SHN), as well as to
study whether this parameter could correlate with the clinical data. The results
showed, that the mean values of the deposit area per mesangial area were similar
in both IgAN and HSN groups. The correlation between electron-microscopic density
of the deposits and hematuria were positive in both IgAN and HSN groups, but only
in IgAN patients this relationship has reached statistical significance.
PMID- 9646677
TI - The Kartagener syndrome--an electron microscopic studies of biopsied mucosa.
AB - We studied 43 tissue samples taken from patients (16 male and 27 women) with
clinical diagnosis of Kartagener's syndrome. The specimens were fixed and
prepared for transmission electron microscopy. After preliminary light
microscopic examination 23 cases were qualified for ultrastructural studies. We
found abnormal number of cilia on the bronchial mucosa cells. The ciliary
structure was abnormal. In several cases we observed lack of inner and/or outer
dynein arms, abnormal location of central microtubules, and abnormal number of
microtubular doublets. Other findings were as follows: replacement of ciliated
cells by goblet ones, mucosal edema and inflammatory infiltrate.
PMID- 9646678
TI - Ultrastructural evaluation of microcirculatory vessels in rheumatoid synovial
membrane.
AB - Since morphological lesions in microcirculatory vessels are often difficult to be
found in the light microscope, the electron microscope investigations were
performed on the synovial membrane biopsy specimens from 70 patients with
rheumatoid arthritis (RA). Most common lesions referred to venules, capillaries
and arterioles were swelling and proliferation of endothelial cells, adherence of
lymphocytes, monocytes and neutrofiles to the endothelium, their margination and
diapedesis. Also destructive changes in the endothelial cells, basement membrane
thickening due to their multiplication and microthrombi were observed. Platelet
aggregates, fibrin, fragments of desintegrated cells and deposits of
granulofibrillary substance corresponding to fibrinoid necrosis were frequently
seen. In 7 patients, lesions of this kind were found only in electronograms. It
can be assumed that the evaluation of ultrastructural changes in the
microcirculatory vessels may be of great significance as a complementary
diagnostic examination in future determination of RA progression and further
prognostication.
PMID- 9646679
TI - Intermediate cells in chronic pancreatitis--ultrastructural observations.
AB - Ultrastructural evaluation of the pancreas resected due to advanced chronic
pancreatitis revealed the presence of numerous intermediate cells exhibiting both
the morphologic features of the exocrine-acinar cell and those of the endocrine
cell of Langerhans'islets in 3 out of 5 cases examined. The analysis of
ultrastructural pictures showed a predominance of acinar-alpha, beta cells,
although acinar-alpha and acinar-beta cells were also found. The role of an
increases in the number of intermediate cells in chronic pancreatitis is not
clear and requires further investigations.
PMID- 9646680
TI - Primary intracranial malignant fibrous histiocytoma--ultrastructural study.
AB - Malignant Fibrous Histiocytoma is the most common soft tissue sarcoma in adults
with the majority of cases that occur in patients between 50-70 years and 64% of
cases occurs in male. Most commonly it arises in extremities (lower 49% and upper
19%), less often in the abdomen (16%) and very rare in head localization (3%)
[5]. Typically macroscopically it is a multilobulated, gray-white, fleshy mass
between 5-20 cm of diameter. In light microscopy this tumour has a highly
variable morphologic pattern and manifests a broad range of histological
appearance. It has been classified into the following subtypes: storiform
pleomorphic, myxoid, giant cell, inflammatory and angiomatoid. The first two
subtypes are more frequent than others. The aim of this report is to present the
electronmicroscopic features of giant cell type of MFH localized in head.
PMID- 9646681
TI - Ultrastructural evaluation of hepatocytes membranes and changes in cytosolic
enzymes distribution in methanol intoxication.
AB - Acute methanol intoxication causes metabolic and structural disturbances of liver
cells. The aim of this paper, therefore, was to evaluate the ultrastructure of
liver cells membrane and the amount of lipid peroxidation products, as well as
the concentration of marker enzymes of liver damage (ALT and AST) in blood serum.
The experiment was done on Wistar rats which once received intragastrically 6,0 g
methanol/kg b.w. as a 50% solution. The animals were decapitated 6, 12 and 24 h
and 2, 5 and 7 days after the methanol administration. The liver was evaluated
under transmission electron microscope and lipid peroxidation products were
determined in the liver homogenate. The serum ALT and AST activity were also
assayed. The biochemical results indicate the increase in lipid peroxidation
products. The consequence of this is probably the membrane liver cell damage
visible in the electron microscope.
PMID- 9646682
TI - Ultrastructural evaluation of lysosomes and biochemical changes in cathepsin D
distribution in hepatocytes in methanol intoxication.
AB - Methanol oxidation is accompanied by free radicals and formaldehyde formation. It
is likely to cause damage of lysosomal membranes. Lysosomal ultrastructure under
transmission electron microscope and biochemical localization of cathepsin D were
estimated after rats intoxication with methanol. The examination was carried out
6, 12 and 24 h and 2.5 and 7 days after intoxication. Ultrastructural examination
showed that methanol causes extension of Golgi apparatus cisterns and an increase
in a number of lysosomes. From 12 h to 2 days lysosomes were characterized by
damage of structure of membrane enclosing lysosomes. During the first days of
intoxication activity of cathepsin D decreased in lysosomes and increased in
cytosol. These changes may lead to uncontrolled extralysosomal proteolysis in the
liver cells and to the onset of liver tissue destruction.
PMID- 9646683
TI - The influence of partial gastrectomy on the ultrastructural changes in the liver-
an experimental animal model.
AB - The aim of our studies was to evaluate the ultrastructural changes in the liver
in rats after partial gastrectomy. The studied group consisted of 19 Wistar
strain rats. In 15 animals partial gastrectomy was done. The control group
underwent laparotomy, only. All tissue material was fixed and then prepared in a
routinous way for histological and electron microscopy studies. During
histological examinations no abnormalities were found. On the ultrastructural
level (in tissue samples taken from animals, no more then 4 months after
gastrectomy) we found mitochondrial degeneration, vacuolization of cytoplasm,
abnormalities in the nuclei and increased activity of B-K cells. The focal
necrosis of the hepatocytes was also observed. In tissue samples from animals
after 4 to 12 months after primary operation we found increasing number and size
of lipid vacuoles in the cytoplasm of hepatocytes The number of Ito cells
increased, also. The gastrectomy caused only minimal ultrastructural changes in
the liver tissue within the period of observation. Those changes described above
may result from numerous metabolic derangements found after gastrectomy.
PMID- 9646684
TI - Ultrastructural studies of the effect of pentoxyfylline on the hepatic cell of
the rat with simultaneous administration of cyclophosphamide.
AB - Ultrastructural examinations carried out on liver specimens collected from Wistar
rats revealed that single administration of cyclophosphamide in a dose of 150
mg/kg body weight produced changes in the cytoplasmic structures, particularly in
the smooth endoplasmic reticulum and mitochondria. The changes were reversible
and subsided 14 days following cyclophosphamide administration. Administration of
pentoxyfylline to rats in a dose of 30 mg/kg b.w./day for 10 days induced
structural alterations in the intracytoplasmic structures of hepatocytes, similar
to those caused by cyclophosphamide, although more intensified in the vicinity of
the vascular pole. The pentoxyfylline-induced changes in hepatocytes retreated
already 4 days after its withdrawal and can be considered adaptative.
Simultaneous administration of both drugs to rats resulted in enhanced metabolic
disturbances in hepatocytes and dissociation of adaptative mechanisms manifesting
themselves in irreversible morphological changes in the intracytoplasmic
structures and in the occurrence of collagen in the intercellular spaces.
PMID- 9646685
TI - Cyclophosphamide in diffuse lung damage.
AB - Some cyclophosphamide toxic effects on lung tissue are presented.
Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung
tissue changes caused by that agent were characterized. Attention was focused on
BAL evaluation as a useful method in the monitoring of lung tissue damage degree.
PMID- 9646686
TI - Effects of pentoxifylline on some peripheral blood parameters and haemostasis in
acute pulmonary tissue injury after cyclophosphamide.
AB - Cyclophosphamide (CP) is one of the widely used cytostatic drugs, with a strong
toxic influence on pulmonary tissue. Experimental works have shown that a single
high dose of CP causes injury to all elements of the interalveolar septum,
especially to the alveolar endothelial and epithelial cells. The aim of this work
was to evaluate the influence of pentoxifylline (PTXF) (30 mg/kg b.w.) on the
ultrastructure of lungs capillaries and blood cell count as well as plasma
fibrinogen levels in Wistar rats after intraperitoneal injection of 150 mg/b.w.
CP. We established that in the doses applied PTXF had no statistically
significant influence on the number of leukocytes and erythrocytes determined in
the left ventricular blood of rats receiving CP, while the number of white cells
from animals given PTXF only was higher than in controls. There was a smaller
decrease in the number of platelets (p < 0.05) and smaller reduction in
fibrinogen level (p < 0.01) in the serum of PTXF-CP animals than in the CP group.
The results obtained suggest a protective effect of PTXF on CP induced changes,
which have been evidenced in some of the parameters examined. Ultrastructural
examinations found the lungs to be the organ of extramedullary thrombocytopoiesis
in CP-treated animals and revealed that platelet accumulation in the system of
lung capillaries was a potential cause of the decrease observed in the number of
blood platelets following CP administration.
PMID- 9646687
TI - Cyclophosphamide-induced changes of serum angiotensin converting enzyme activity
and pulmonary microvessels ultrastructure.
AB - The effect of cyclophosphamide (CP) on the ultrastructure of the lung tissue and
the activity of angiotensin converting enzyme (ACE) in serum was evaluated in
rats. The animals were given cyclophosphamide (CP) in a single intraperitoneal
dose of 150 mg/kg b.w. ACE activity was evaluated in the blood serum collected
from the left ventricle of the heart using the spectrophometric method. In all
time subgroups, the CP-receiving animals showed a decrease in ACE activity.
Ultrastructural examinations of CP-treated animals revealed increased adhesion of
neutrophiles and monocytes to the damage endothelium of the alveolar septa
vessels and focally accumulation of the platelets.
PMID- 9646688
TI - Microenvironment of Morris hepatoma 5123 metastases to the lungs--ultrastructural
analysis of intratumour injections of rhTNF-alpha.
AB - We analysed the effect of rhTNF-alpha on the development of Morris hepatoma 5123
spontaneous metastases to the lungs of Buffalo rats. After intratumour
administration of the cytokine the lungs were found to contain scarce metastatic
foci. In precapillaries and capillaries neoplastic cells were single or in small
clusters, without contact with endothelial cells. Endothelial cells showed high
pinocytic activity and frequently tightly closed vascular lumen. The stroma of
interalveolar septa and the capillary bed contained multiple eosinophils.
Moreover, eosinophils, histiocytes and monocytes mixed with abundant collagen
fibres were found on the margin of single small metastatic foci and among
necrotic neoplastic cells.
PMID- 9646689
TI - Ultrastructure of bone marrow megakaryocytes in experimental haemorrhagic shock
in rats. I. Correlation between ultrastructure of MK nuclei and DNA ploidy.
AB - The correlation was described between the ultrastructural picture and DNA mass
content of MK nuclei in experimental haemorrhagic shock in rats. Significant
disproportions were revealed between the morphological pictures and the ploidy of
MK nuclei in the successive phases of the shock. Abnormalities of the maturation
of marrow MK nuclei were found in the first hours of the shock, being most
pronounced in the 24th hour.
PMID- 9646690
TI - Ultrastructure of bone marrow megakaryocytes in experimental haemorrhagic shock
in rats. II. Correlation between ultrastructure of MK cytoplasm and
thrombopoiesis.
AB - Ultrastructural evaluation was performed of the MK cytoplasm in the successive
phases of experimental haemorrhagic shock in rats. Qualitative abnormalities were
revealed in the intracytoplasmic structures of MK. Platelets in the circulating
blood were evaluated. A correlation was found between the changes in the
intracytoplasmic organelles and the number and biological activity of blood
cells. The results obtained indicate significant disturbances in the functioning
of the thrombopoietic system in experimental haemorrhagic shock, which are caused
by alterations within the intracytoplasmic structures of MK and lead to platelet
production from morphologically differentiated but functionally immature MK.
PMID- 9646691
TI - A comparison of the peritoneal cell population of pregnant rabbits after LPS or
TNF-alpha induced septic shock.
AB - Septic shock is a catastrophic consequence of invasive infection. Unfortunately,
recent advances in surgical and medical sciences have not significantly reduced
the overall mortality from septic shock. Bacterial antigens stimulate a cascade
of cytokine release; each cytokine helps the host to overcome infection, but
their excessive production causes them to trigger events that lead to septic
syndrome and shock. Tumour necrosis factor (TNF-alpha) has a pivotal role in
orchestrating the events leading to septic shock. Intraperitoneal administration
of certain substances can increase the number and phagocytic activity of cells,
which reach naturally the site of infection. Activation of the immunity cells in
the peritoneal cavity and their immunocompetence are found to be responsible for
the organism protection against abdominal cavity infections. Macrophages,
lymphocytes and granulocytes of low activity in the non-stimulated peritoneal
cavity become significant due to the influence of numerous biologically active
substances. This study was designed to determine the peritoneal response to local
administration of LPS or TNF-alpha in the course of experimental septic shock.
PMID- 9646692
TI - Morphometric and ultrastructural studies of the spinal sensory ganglia in the
course of sciatic nerve regeneration in rats intoxicated with ethanol.
AB - The aim of the study was to examine morphological changes in the spinal dorsal
ganglia (from which sensory fibres of the sciatic nerve extend) in animals
intoxicated with ethanol, in which the sciatic nerve was transected and then
sutured. By means of morphometric methods using a computer system of picture
analysis and in ultrastructural examinations it was found that ethanol
administered to rats to drink for 3 months caused only slight morphological
alterations in the sensory nerve cells of the spinal vertebral ganglia on the non
operated side. However, ethanol or its metabolites destroyed the regenerating
sensory nerve cells of the spinal vertebral ganglia of the transected and then
sutured sciatic nerve.
PMID- 9646693
TI - Vasa vasorum of blood and lymph vessels in the broad ligament of the sheep uterus
analyzed by scanning electron microscopy.
AB - The morphology of vasa vasorum of the blood and lymph vessels in the broad
ligament of the uterus was examined in 12 adult ewes. The technique of vascular
corrosion casts with the usage of Mercox resin allows multiple surveys of a three
dimensional organization of vascular networks under a scanning electron
microscope (SEM). The study was appended by tissue pieces dried by the critical
point method for SEM and semi-thin sections stained with toluidyne blue for light
microscopy. Vasa vasorum surrounded both the larger vessels and the lymph vessels
emanating from the ovary and the uterus. Significant differences in location and
intensity of vasa vasorum in blood vessels were observed. They were less
developed in the first part of the ovarian and the uterine arteries than in their
smaller branches. Significantly large, two- or even three-layer vasa vasorum
surrounded the ovarian and the uterine branches of the ovarian artery as well as
the ovarian veins in the area of mesovarium. In the other areas of the broad
ligament of the uterus, arterial vessels of similar sizes usually had a single
layer vasa vasorum. The lymph vessels leaving the ovary and uterus were
surrounded by dense, although usually single-layed, microvascular network. The
presence of vasa vasorum on relatively small blood and lymph vessels of the broad
ligament of uterus indicates their particular functions that are probably
connected with the estrous cycle or pregnancy and changes of blood flow rate
entering the ovary and uterus. However, the presence of significantly developed,
multi-layer vasa vasorum networks on only some of the blood vessels indicates
that it is probably one of the vessels morphological adaptations to serve the
counter-current transfer of biologically-active regulators in the area of the
broad ligament of the sheep's uterus.
PMID- 9646694
TI - Ultrastructural changes on the root surface in "pressure zone" after experimental
movement of teeth in young rats fed a low calcium and vitamin D-deficient diet.
AB - Dietary calcium and vitamin D-deficiency, as a potential biological factor in
etiopathogenesis of root resorption occurring during orthodontic tooth movement,
still remains controversial. The aim of the present investigation was to assess
the ultrastructural changes on the surface of the root in "pressure zone" after
orthodontic tooth movement in rats fed a low calcium and vitamin D-deficient
diet. The studies were carried out on 20 young Wistar rats. The results from the
scanning electron microscopic showed the increased root resorption in "pressure
zone" after orthodontic tooth movement in rats fed a low calcium and vitamin D
deficient diet.
PMID- 9646695
TI - Ultrastructural changes of a tooth root in young rats fed a low calcium and
vitamin D-deficient diet.
AB - The aim of the investigation was to assess the ultrastructural changes of the
roots of the teeth in young rats fed a low calcium and vitamin D-deficient diet.
The studies were carried out on 20 young Wistar rats. The results of the scanning
microscopic observations showed the increased cementolysis and decreased
mineralization of cementum and dentin in rats fed a low calcium and vitamin D
deficient diet. The results indicated that the hard tissues of the teeth, besides
bony system, are also involved in calcium homeostasis in rat organism.
PMID- 9646696
TI - Scanning electron microscopy of the influence of dietary calcium and vitamin D
deficiency on periodontium in the adult rats.
AB - Mandibular bone and teeth in test animals fed a low calcium and vitamin D
deficient diet in comparison to control rats were examined by scanning electron
microscope (SEM). The observations showed increased resorption of the mandibular
bone, increased resorption and decreased mineralization of cementum in the test
group. The study indicated that calcium and vitamin D-deficiency in adult rats is
related with changes of the mandibular bone and teeth.
PMID- 9646697
TI - Preliminary assessment of ultrastructural changes in muscle fibres of rabbits
after electric stimulation.
AB - Studies were carried out on the effect of lateral electric surface stimulation
used to treat lateral idiopathic spinal curvature in children and youth upon
ultrastructural changes in the muscles which take part in spine stabilization.
The experiment was carried out for 3 months on 10 rabbits. It was found that this
stimulation, performed for 9 hours daily for 3 months, resulted in both
progressive and regressive changes. Deviations from a norm suggest that the
stimulation process destroys the sensory part of the reflex arc and chronic
destructure of motoric neuron. In addition to this, overstraining of the muscle
fibres with work was reflected in fibre hypertrophy and changes in the
mitochondria.
PMID- 9646698
TI - Ultrastructural manifestation of pharmacologic inhibition of the activities of
lipases and proteases in the cat carotid body.
AB - This study is based on the premise that if a subcellular element of an organ
performs an appreciable functional role, then its inhibition could influence the
ultrastructural organization of the organ. We addressed this issue in the
investigation on the carotid body, a chemosensory organ, by comparing the
ultrastructure of its parenchyma in phenylmethylsulfonyl fluoride (PMSF)-injected
cat with that of the normal cat. PMSF, an inhibitor of lipases and proteases,
induced degenerative changes chiefly in subcellular components other than the
neurosecretory and synaptic elements being associated with signal transduction.
The study suggests that the inhibited enzymes might also have to do with the
carotid body function.
PMID- 9646699
TI - An immunohistochemical study on the postnatal changes in the C-terminal flanking
peptide of neuropeptide Y (CPON)--positive nerve fibers in pineal gland of the
pig.
AB - Postnatal development of innervation of the porcine pineal gland by C-terminal
flanking peptide of neuropeptide Y (CPON)-immunoreactive nerve fibers was
examined using the immunohistochemical technique. CPON-positive nerve fibers
appeared in the pineal gland of the new-born piglets and formed plexus in the
capsula and connective tissue septa of the gland. The nerve terminals branched
off from the plexus and penetrated into adjacent parenchyma. The number of nerve
fibers immunoreactive to CPON in parenchyma is very low in new-born and 20-day
old piglets. In 7-month-old pigs they created a dense network.
PMID- 9646700
TI - Membrane bounded dense bodies (MBB) of the domestic pig pinealocytes--current
state of knowledge.
AB - The results of our former investigations concerning the pig pinealocyte
organelles named membrane bounded dense bodies (MBB) have been summarized. The
presence of MBB is the most conspicuous morphological feature of pinealocytes of
genus Suidae. The relative volume of MBB in the cell bodies of pinealocytes in
adult domestic pigs ranges from 8% to 16% of whole cytoplasm. On the basis of
their morphology, membrane bounded bodies were divided into two main types: MBB-1
and MBB-2. Dense bodies of MBB-1 type have various inner structure and are
present both in perikaryons and processes of the pinealocytes. Dense bodies of
MBB-2 type are characterised by regular, multilammellar structure and their
presence is restricted to pinealocyte perikaryons. The origin and transformations
of the MBB are enigmatic. The relative volume of dense bodies in the pig
pinealocytes changes during postnatal development and under various physiological
and experimental conditions. The system of dense bodies is controlled by
sympathetic innervation and environmental light. Dense bodies are also influenced
by changes in function of pituitary-gonadal axis in female pigs and by
administration of melatonin. High number of the dense bodies in the pig
pinealocytes, significant changes in their number and inner structure in various
physiological and experimental conditions as well as their exocytosis from
pinealocyte processes suggest that these structures are involved in secretory
processes in the pig pinealocytes.
PMID- 9646701
TI - Diurnal changes in the ultrastructure and volumes of nuclei in liver cells of
Hemidactylus frenatus in variable lighting conditions.
AB - The research was carried out on young, mature specimens of Hemidactylus frenatus.
The diurnal changes in the nucleus ultrastructure, especially changes in the
number of perichromatin granules (PG), were investigated. The results let us come
to the conclusion that the number of PG distinctly changes in twenty four hours
and shows a negative correlation with the nuclei volumes.
PMID- 9646702
TI - Ultrastructure of the calcareous layer eggshell of the turtle Emys orbicularis
(L.). Preliminary study.
AB - The calcareous layer of Emys orbicularis eggshell was examined by scanning
electron microscopy. The layer is composed of well distinguished shell units
which consist of needle-like crystallites radiating outwards from the cores. The
linear structures of the cores on the inner surface appear to be similar to those
in the eggshell of Mauremys caspica. On the inner surface of shell units of eggs
with dead embryos there are flat, conical depressions. This surface in specimens
from unfertilized eggs is almost flat. It may suggest that a developing embryo
derives calcium from the eggshell.
PMID- 9646703
TI - Ultrastructure of premetamorphic taste organs of the Bombina variegata.
AB - Ultrastructural studies of taste organs in tadpoles of Bombina variegata indicate
that these are taste buds (TBs). They occur in the apical parts of papillae of
the mouth cavity lining. Each taste bud consists of taste cells and supporting
cells; no basal cells were found. In the sensory area of taste bud there are two
types of sensory cells: cells with a tuft of short (approximately 1.5 m)
microvilli and cells with a single, longer (up to 3.7 microns) process,
definitely longer than in TBs of other studied species of Anura. Fairly often,
twin TBs were observed.
PMID- 9646704
TI - Ultrastructural changes of Candida albicans under influence of cyclosporin A.
AB - The aim of this study was the assessment of influence of cyclosporin A on
ultrastructural changes of Candida albicans in vitro. Strains of Candida albicans
isolated from woman with chronic vulvovaginitis were used. At the first part of
experiment MIC (minimal inhibitory concentration) of cyclosporin on Sabouraud
medium was assessed. Control plates were also prepared. From plates with Candida
albicans there was observed its visual growth, the yeasts were prepared for
electron transmission microscopic examines. It was found that ultrastructural
changes of Candida albicans cells in the presence of Cyclosporin A. In
particular, the cell wall was thicker and deteriorated. The organelles were
altered in varying degrees and autolysis was observed.
PMID- 9646705
TI - Ultrastructural determination of the early stage of conversion from root
primordia to shoot primordia in vitro cultures of Solanum lycopersicoides Dun.
AB - The object of the research were in vitro cultures of root primordia and the early
stage of conversion from root to shoot primordia cultures (ESCRS) of Solanum
lycopersicoides Dun. The cell ultrastructure of both culture types was studied in
order to determine processes underlying the root and shoot morphogenesis type. It
was found that a change of a morphogenesis type occurs together with
reorganization of aggregate structure and the cell ultrastructural organization.
There were 4 zones detected in root primordia culture aggregates (the surface,
the starch, the division and the differentiation zone) and 3 zones in ESCRS
culture aggregates (the surface, the inner and the differentiation zone). The
differences were observed also in storage substances accumulated in a culture
(starch in root primordia cultures; proteins, lipids and starch in ESCRS ones).
PMID- 9646706
TI - Intermediate cells in the rat pancreas after chronic exposure to lead.
AB - Ultrastructural analysis of the rat pancreas following the long-term exposure to
lead revealed the presence of numerous intermediate cells in animals receiving
lead acetate in doses of 500 ppm and 1000 ppm for 4 and 6 weeks. The cells
included acinar-beta, beta-acinar and intermediate cells containing two kinds of
endocrine granules- alpha and beta, and zymogen granules.
PMID- 9646707
TI - [Classification of distal radius fractures--comparison of spiral CT with
conventional roentgen image].
PMID- 9646708
TI - [Multifocal malignant gastrinoma in MEN-I syndrome].
PMID- 9646709
TI - [Intestinal imaging: 1997 literature update].
PMID- 9646710
TI - [Value of double-contrast imaging of the small intestine in diagnosis of
symptomatic jejunal diverticulosis].
PMID- 9646711
TI - [Gas in the portal vein system].
PMID- 9646712
TI - [Radiologically detectable changes in the radial annular ligament and the
supinator muscle of the domestic cat (Felis catus)].
AB - Elbow joints of a random sample of 59 cats were investigated by means of X-rays
and dissection as well as histologically and by making cuts through synthetic
resin-embedded joints. Bone-dense shadow craniolateral to the elbow joint was
observed in X-ray images of 23 limbs (about 20%). Furthermore 8 of these 23 elbow
joints (about 7%) showed signs of arthrotic alteration. Histologic examination
revealed one or more centers of metaplasia of varying status of development of
the annular ligament of the radius. Alterations varied from chondroid metaplasia
to mineralisation and ossification. They turned out to be located in the area
where the annular ligament of the radius crosses the tendon of origin of the
supinator muscle and are considered to be a reaction of tough connective tissue
to mechanical stress. Compressive forces seem to be less responsible than tensile
stress. As soon as bone-dense shadow is observed in X-ray images, alterations
have grown so far as the annular ligament of the radius as well as the tendon of
origin of the supinator muscle are affected.
PMID- 9646713
TI - [182 offspring of cows with bovine spongiform encephalopathy (BSE) in
Switzerland. 1. Clinical findings].
AB - This study involved 182 calves, heifers and cows that were the first generation
progeny of cows with bovine spongiform encephalopathy (BSE). All animals
underwent clinical and neurological examinations. Blood, milk, urine, ruminal
fluid and cerebrospinal fluid samples were examined. Each cow underwent a
specific examination for BSE which included assessment of behaviour, sensitivity
and locomotion. This examination was performed twice, and there was very good
agreement between the results. The most common symptom was nervousness (14
animals). In the first examination, 68 animals were mildly to moderately
sensitive to touching of the head, 44 animals were hypersensitive to a halogen
light and 35 animals were hypersensitive to a camera flash. Twenty-four animals
reacted by kicking when the hindlimbs were touched with a broom. None of the
animals had disturbances in locomotion. Based on the interpretation of all
findings and the comparison of the results of the first and second examinations,
173 animals were diagnosed as free of BSE. In 9 animals, the disease could not be
ruled out; however, it could not be confirmed in any of them. Histological and
immunohistochemical examinations of the brain of all animals were negative for
BSE (see Part 2 of the study for details). The results of this study indicate
that abnormal clinical findings may occur in clinically healthy cattle. However,
none of the progeny of cows with BSE exhibited clinical signs typical of BSE,
such as disturbances in behaviour; sensitivity and locomotion.
PMID- 9646714
TI - [182 offspring of cows with bovine spongiform encephalopathy (BSE) in
Switzerland. 2. Epidemiology and pathological findings].
AB - In order to detect lesions of a spongiform encephalopathy and/or accumulation of
the protease resistant prion protein (PrPres), 182 offspring of cows affected
with BSE were examined neuropathological and immunohistochemically. Neither
spongiform encephalopathy nor PrPres accumulation were found. In seven animals
other neuropathological lesions were seen, significant ones in three. Because of
the small risk of exposure to contaminated feed in these animals, nearly all of
which were born after the introduction of the protein feed ban for ruminants, the
occurrence of spongiform encephalopathy in this series of BSE offspring would be
suggestive of maternal transmission. However, the value of the study in this
respect is quite limited. Only half of the animals were old enough to develop
clinical and pathological evidence of the disease. If a maternal effect on the
risk for the offspring is only to be expected during the last 6 months of the
incubation of the dam as suggested by British investigations, only few animals in
this study would fulfil the requirement of having been born during this critical
period. Since it cannot be entirely excluded that the BSE agent transiently
invades extraneural tissues in the early stages of infection, the above mentioned
restriction to the final 6 months of the incubation time of the dam would not
necessarily be applicable to all situations. We concluded that this study
supports previous observations according to which maternal transmission of BSE is
at best a rare event.
PMID- 9646715
TI - [Is dirofilariasis in dogs spreading in south Switzerland?].
AB - Microfilarial infections could be detected by the Difil Test in 11 (2.2%) of 479
blood samples of clinically asymptomatic dogs from the South of Switzerland.
Dirofilaria repens and D. immitis were identified in 3 (0.6%) and 8 dogs (1.6%),
respectively, by the acid phosphatase activity of the microfilariae. 10 dogs with
microfilaremia had been abroad or a stay outside Switzerland could not be
excluded. One dog diagnosed with D. immitis could have had acquired the infection
in the canton Tessin according to information given by the owner. Dogs with
microfilaremia are a potential source of infection for mosquitoes. An indigenous
cycle of infection in the South of Switzerland is possible since the mean average
temperature in summer is above 18 degrees C which is necessary for optimal
parasite development in the vector. A strict control of imported dogs or animals
exposed to the disease in endemic regions as well as the therapy of infected dogs
in the South of Switzerland is advisable.
PMID- 9646716
TI - Farewell to old decency: the demise of handwritten medical records.
PMID- 9646717
TI - Quetiapine: a new atypical antipsychotic.
AB - Quetiapine has recently been approved for treatment of psychotic disorders. In
short term (6 weeks) trials this atypical antipsychotic was shown to be as
efficacious as the standard antipsychotics for the treatment of the positive
symptoms of schizophrenia without causing any extrapyramidal symptoms or increase
in the prolactin levels. Its efficacy for treating the negative symptoms was
variable. Preliminary observations suggest its potential to improve the cognitive
deficits of schizophrenia. It is metabolized by the p450 CYP 3A4 system with an
estimated elimination half life of 6 hours. The optimal treatment is 300 mg to
400 mg/day in two to three divided oral doses. The most common side effects
include dizziness, hypotension, somnolence and weight gain. Changes in the ECG,
the thyroid hormone and hepatic enzymes levels appear to be clinically
insignificant. Quetiapine interacts with phenytoin, carbamazepine, barbiturates,
rifampin and glucocorticoids; and coadministration with these drugs may require
dosage adjustment. Doses need not be adjusted when fluoxetine, imipramine,
haloperidol and resperidone are coadministered. Quetiapine may enhance the
effects of antihypertensive agents and may antagonize those of levodopa and
dopamine. Long term efficacy of quetiapine has not been determined. Also
undetermined are its effectiveness for treating the first episode and treatment
refractory schizophrenia. Data suggest that quetiapine may be used for the
management of psychotic disorders in patients who may not tolerate the side
effects of the typical antipsychotics and clozapine. It may also be helpful in
patients whose psychotic manifestations did not adequately respond to risperidone
and olanzapine.
PMID- 9646718
TI - Vancomycin levels: to draw or not to draw.
PMID- 9646719
TI - Cure of Goodpasture's disease.
AB - Goodpasture's Disease is an explosive multisystem disease presenting initially as
a pulmonary-renal syndrome. There is often little margin for error in making an
early correct diagnosis to avoid respiratory and renal failure. Complications of
invasive diagnostic testing and aggressive immunosuppressive treatment often lead
to other organ dysfunction due to infection, hemodynamic disturbances, fluid and
electrolyte challenges, and nutritional deficiency. Artificial organ therapy is
often needed for pulmonary and renal support, for immunomodulation, and for
nutritional replacement. The outcome is often considered satisfactory if the
patient survives the acute presentation. Persistent organ failure is quite often
the case, especially renal failure. Quality of life is often improved if there is
subsequent renal transplantation. By then the patient may be considered "cured".
Two cases are described below, contrasting young and elderly white females both
in previous good health who developed rapid onset of Goodpasture's disease. One
was cured after transplantation, and one was cured without transplantation. The
severity of the renal involvement was the same for both patients. Cure of
Goodpasture's Disease in the native kidneys is uncommon; a review of the
literature is provided.
PMID- 9646720
TI - Fetal growth and development.
AB - The foetal growth is, for the greater part, determined genetically. There are,
however, favouring and inhibiting factors, which influence this growth. In such a
matter, the mother, the placenta and the foetus play an important part. The
mother shows as well metabolic as vascular adaptations. The placenta must let
through nutrients and oxygen; the uteroplacental circulation is characterized by
a high flow, together with a low vascular resistance. The foetus itself plays an
important part owing to its own growth factors. The principal growth factors are
insulin and the growth factors analogous to insulin. The slowing up of the intra
uterine growth is the consequence of genetic factors or of the decrease of the
growth-potential. The real cause is, however, mostly a decrease of the vascular
adaptation in the mother or a diminution of the uteroplacental circulation. The
vascular causes usually induce an asymmetrical delay in the growth; foetal causes
induce a symmetrical retardation. An exaggerated growth of the foetus--or
macrosomy--is mostly due to an excessive inflow of nutrients: this is the case
when a pregnant woman is suffering from diabetes. During the former years, it has
become evident that abnormalities of the foetal growth influence the later life
of people.
PMID- 9646721
TI - New perspectives for the treatment of HIV infections.
AB - Eleven compounds have now been licensed for the treatment of HIV (human
immunodeficiency virus) infections: the nucleoside/nucleotide reverse
transcriptase inhibitors (NRTIs) zidovudine (ZDV, AZT), didanosine (DDI),
zalcitabine (DDC), stavudine (D4T) and lamivudine (3TC), the nonnucleoside
reverse transcriptase inhibitors (NNRTIs) nevirapine and delavirdine, and the
protease inhibitors saquinavir, ritonavir, indinavir and nelfinavir. Several
other compounds that interact with the reverse transcriptase or protease or other
targets of the viral replication cycle are in clinical or preclinical
development. High expectations are vested in the acyclic nucleoside phosphonates
PMEA and PMPA (which have proved clearly efficacious against HIV infections in
phase II/III and phase I/II trials, respectively) and the bicyclam derivatives,
which have recently been shown to block HIV infection through interference with
the viral co-receptor CXCR4 (fusin). It has become increasingly clear that only
the concomitant use of several anti-HIV agents combined can completely suppress
HIV replication and offer the potential for a complete cure. To this end, the
different compounds should be administered from the start at sufficiently high
doses, and treatment should be started as soon as possible after the infection.
Under these conditions, HIV-drug resistance development could be prevented, and
progression to AIDS, arrested. Whether this procedure would also be able to
eradicate the virus from the organism still needs to be proven.
PMID- 9646722
TI - [Transport of drugs across the blood-brain barrier].
AB - The blood-brain barrier prevents an indifferent medicine existing in the blood to
enter also in the brain. This barrier has got an anatomical base: it is first
consisting in a cerebrovascular layer of endothelial capillary vessels of the
peripheral tissue. It is moreover covered by outgrowths of the flial cells, which
are called astrocytes. There are, for that reason, important limits to a size of
molecules which can reach the cerebral tissue through a paracellular way (through
what is called in English "tight-junctions"). Most medicines must use the
transcellular way. Lipophily is necessary to follow that way. Year after year, it
appeared, thanks to a comparative study of the substances, that there exists-
grosso modo--a positive correlation between the lipophilic level and the
permeation-level of a substance in the cerebral tissue. There are, however,
several exceptions: it is so that hydrophilic substances, possessing an important
nourishing function (such as glucosis, amino-acids) seem to penetrate much more
easily than we could expect when we consider their physicochemical
characteristics. This is the result of the fact that there exist specifical
transport-mechanisms for these substances at the level of the endothelial cell
membranes, allowing the penetration of such substances. There exist, on the
contrary, lipophilic components that penetrate the cerebral tissue much less
strongly than we should expect. This happens because there also exist pumping
mechanisms at the level of the hemato-encephalic barrier. The concerning
substance, which was recently discovered is the "glycoprotein P", which is also
responsible for the "multi-drug-resistance" and for the resistance of tumors to
cytostatics. This phenomenon relies on a very efficient pumping of substances
which have penetrated cells in which this protein expressed itself in the
membranous structure. In order to obtain a better understanding of the function
of the hemato-encephalic barrier, comprising the transport of medicines, it is
most important to have reliable experimental models. It is to that aim that,
during former years, the technique of cultivating endothelial cerebrovascular
cells was developed. These cells are isolated from brains of calves or rats and,
subsequently, cultivated on a laboratory medium; about a week later, they have
grown a single and confluent layer. This layer represents a kint of "hemato
encephalic barrier" in vitro, which allows us to study the transfer of substances
through the layer and thus also the details concerning the transport mechanisms,
as well as the factors influencing the permeability of the cells-layer (for
instance the inflammatory stimuli). Concerning the "in vivo" research, the
technique of intracerebral microdialysis in lab-animals proved to be very
promising. In order to effect this microdialysis, a semipermeable microcannula is
introduced in the brain tissue, across which an iso-osmotic liquid is being
injected continuously. The substances staying in the interstitial liquid of the
cerebral tissue will diffuse under the influence of a concentration gradient,
into the dialysing liquid and they will also be ready to be analysed. Thanks to
this technique, it is possible to follow, in the same animal, the evolution of
the concentration in the brain of a substance which has, for instance been
injected in a peripheral region. In this way, we obtain, indirectly and in vivo,
informations about the functioning-process of the "hemato-encephalic barrier". We
can, moreover, effect measures on a specific spot, for instance in tumoral brain
tissue: this allows us to study the influence of specific transport-mechanisms.
These rather recent techniques, as well in vitro as in vivo, will allow us, in
consequence, to increase, during the next years, our understanding of the way the
hemato-encephalic barrier functions as to the transfer of medicines towards the
central nervous system. This understanding may lead us to new strategies allowing
PMID- 9646723
TI - RNA editing: trypanosomes rewrite the genetic code.
AB - The understanding of how genetic information is stored and expressed has advanced
considerably since the "central dogma" asserted that genetic information flows
from the nucleotide sequence of DNA to that of messenger RNA (mRNA) which in turn
specifies the amino acid sequence of a protein. It was found that genetic
information can be stored as RNA (e.g. in RNA viruses) and can flow from RNA to
DNA by reverse transcriptase enzyme activity. In addition, some genes contain
introns, nucleotide sequences that are removed from their RNA (by RNA splicing)
and thus are not represented in the resultant protein. Furthermore, alternative
splicing was found to produce variant proteins from a single gene. More recently,
the study of trypanosome parasites revealed an unexpected and indeed counter
intuitive genetic complexity. Genetic information for a single protein can be
dispersed among several (DNA) genes in these organisms. One of these genes
specifies an encrypted precursor mRNA that is converted to a functional mRNA by a
process called RNA editing that inserts and deletes uridylate nucleotides. The
sequence of the edited mRNA is specified by multiple small RNAs, named guide
RNAs, (gRNAs) each of which is encoded in a separate gene. Thus, edited mRNA
sequences are assembled from multiple genes by the transfer of information from
one type of RNA to another. The existence of editing was surprising but has
stimulated the discovery of other types of RNA editing. The Stuart laboratory has
been exploring RNA editing in trypanosomes from the time of its discovery. They
found dramatic differences between the mitochondrial gene sequences and those of
the corresponding mRNAs, which indicated editing by the insertion and deletion of
uridylates. Some editing was modest; simply eliminating shifts in sequence
register of minimally extending the protein coding sequence. However, editing of
many mRNAs was startingly extensive. The RNA sequence was essentially entirely
remodeled with its sequence more the result of editing than the gene sequence.
The identities of genes for such extensively edited RNA were not recognizable
from the DNA sequence but they were readily identifiable from the edited mRNA
sequence. Thus, despite the complex and extensive editing the resultant mRNA
sequence is precise. Characterization of partially edited RNAs indicated that
editing proceeds in the direction opposite to that used to specify the protein
which reflects the use of the gRNAs. The numerous gRNAs that are used for editing
are encoded in the DNA molecules whose role was previously a mystery. Using
information gained in our earlier studies, the Stuart group developed an in vitro
system that reproduces the fundamental process of editing in order to resolve the
mechanism by which it occurs. They determined that editing entails a series of
enzymatic steps rather than the mechanism used in RNA splicing. They also showed
that chimeric gRNA-mRNA molecules are aberrant by-products of editing rather than
intermediates in the process as had been proposed. Additional studies are
exploring precisely how the number of added and deleted uridylates is specified
by the gRNA. The Stuart laboratory showed that editing is performed by an
aggregation of enzymes that catalyze the separate steps of editing. It also
developed a method to purify this multimolecule complex that contains several,
perhaps tens of, proteins. This will allow the study of its composition and the
functions of its component parts. Indeed, the gene for one component has been
identified and its detailed characterization begun. These studies are developing
tools to explore related processes. An early finding in the lab was that the
various mRNAs are differentially edited during the life cycle of the parasite.
The pattern of this editing indicates that editing serves to regulate the
alternation between two modes of energy generation. This regulation is
coordinated with other events that are occurring during the life c
PMID- 9646724
TI - Adaptation and information in ontogenesis and phylogenesis. Increase of
complexity and efficiency.
AB - Adaptations during phylogenesis or ontogenesis can occur either by maintaining
constant or by increasing the informational content of the organism. In the
former case the increasing adaptations to external perturbation are achieved by
increasing the rate of genome replication; the increased amount of DNA reflects
an increase of total but not of law informational content. In the latter case the
adaptations are achieved by either istructionist or evolutionary mechanism or a
combination of both. Evolutionary adaptations occur during ontogenesis mainly in
the brain-mind, immunological and receptor systems and involve a repertoire of
receptors that are., clonally distributed, genome-conditioned and amplified by
somatic mutation. Specificity and intensity of responses are achieved a
posteriori as a result of natural selection of the clones. The major adaptations
during phylogenesis are accompanied by increased complexity. They have been
attributed to shifts, short in time and space, against the entropic drive and
thus occur notwithstanding the entropic drive and the second law of
thermodynamics. The alternative view, is that the generation of complexity is due
to the second law of thermodynamics in its extended formulation which includes
Prigogine's theorem of minimum entropy production. This view requires however
that natural selection provides the biological system with structures that bring
the reactions within Onsager's range. The hierarchical organization of the
natural world thus reflects a stratified thermodynamic stability. As the
evolutionary adaptations generate new information they may be assimilated to
Maxwell demon type of processes.
PMID- 9646725
TI - The public science of Louis Pasteur: the experiment on anthrax vaccine in the
popular press of the time.
AB - The paper focuses on Pasteur's public experimentation of the anthrax vaccine
(Pouilly-le-Fort, 1881) as portrayed in the English and French popular press of
the time. It is argued that this 'popular' level of representation did not merely
provide additional publicity for Pasteur's ideas. Rather, the nature and meaning
of the experiment itself and of the related controversy on immunisation were
substantially negotiated and shaped within the public arena. The multifold
consequences of this framing at the public level are explored. In particular,
attention is drawn to the relationships that in such process were established
with other issues debated at the same time in the arena, namely homeopathy,
vivisection and vaccination.
PMID- 9646727
TI - Tufte, perception and visual representation: some bio-social context.
PMID- 9646726
TI - The discovery of Chagas' disease and the formation of the early Chagas' disease
concept.
AB - This paper attempts to show how leading contemporary disciplines influenced the
discovery of Chagas' disease and the formation of the early disease concept.
Chagas was among the first generation of Brazilian trained scientists who
incorporated modern principles of tropical medicine in its research. Thus, Chagas
was familiar with characteristics of vector borne tropical diseases such as
malaria and yellow fever. The detection of a hitherto unknown trypanosome in the
gut of a reduviid bug prompted him to search for a related vector borne disease.
Among the disciplines that were influential on Chagas' discovery and early
disease description were pathology, entomology and parasitology. Parasitology as
a new discipline was of crucial importance to tropical medicine and had a
political dimension in the context of colonial medicine. Hence, leading
scientists in tropical medicine were located in European countries and in the
United States of America. One of these was the German Schaudinn School of
Protozoology. The early description of American Trypanosomiasis can also be seen
as a reflection of the Schaudinn School of Protozoology which dominated Chagas'
scientific orientation towards parasitology with regard to the interpretation of
the observed phenomena of the life cycle and the morphology and biology of T.
cruzi. The first Chagas' disease concept was based on research of the biology and
entomology of the trypanosome and its vector as well as on pathological studies
of fatal cases. This concept was characterized by a confusion of some of the
chronic forms of the disease, as iodine deficiency and goitre were endemic in
some rural regions in Brazil. Therefore, early concepts of the disease faced
strong opposition and even raised doubts about its existence.
PMID- 9646728
TI - Penmanship. Rx for errors.
PMID- 9646729
TI - Hospital closings. Sometimes less is less.
PMID- 9646730
TI - What they don't know hurts.
PMID- 9646731
TI - Be it ever so jumbled.
PMID- 9646732
TI - The right to appeal.
AB - When health plans say no, most patients back off. Only a few states guarantee
independent reviews for treatment denials, but politicians and activists want to
change that. The right to redress is the flash point of a larger movement to
mandate consumer rights under managed care.
PMID- 9646733
TI - Sizing up the sickest.
AB - It's lurking all the time: Clues about patients prone to costly medical crises
are already sitting in your computer system. The past opens a window on the
future--if only you can ID the most vulnerable and guard against their getting
sick in the first place.
PMID- 9646734
TI - Blue on Blues.
AB - Activists and regulators won't let Blue Cross & Blue Shield plans forget their
roots. In fact, when these historic not-for-profits announce intentions to merge
with other Blues or go for-profit, states demand repayment for years of foregone
taxes. Charity has become the spoiler, dashing deal after deal.
PMID- 9646735
TI - Uneasy marks.
AB - Germany earned a reputation as a European nirvana, marked by a booming job market
and generous health and social programs. Now, thanks to the high costs of
rebuilding the former East Germany and other factors, national health programs
face cutbacks. But just about everyone has a stake in guarding the status quo.
PMID- 9646736
TI - Finances. Kaiser's squeeze play.
PMID- 9646737
TI - Consolidation. An emergent merger.
PMID- 9646738
TI - Hospital pulse--October 1997.
PMID- 9646739
TI - Software support. Hung up on response time.
PMID- 9646740
TI - Cumulative trauma disorders of the upper extremity.
PMID- 9646741
TI - Clinical lectures on scriveners' palsy, or the paralysis of writers. 1864.
PMID- 9646742
TI - Nerve injury in repetitive motion disorders.
AB - Nerve compression in repetitive motion disorders is being recognized with
increasing frequency. The pathophysiology of chronic nerve compression spans a
broad spectrum beginning with subperineurial edema and progressing to axonal
degeneration. These changes depend on the amount and duration of the compressive
forces. Certain postures or positions in the upper extremity will increase
pressures around certain nerves increasing pressure exposure. Evaluation of these
patients with chronic nerve compression should include examination at all levels
of potential entrapment in the upper extremity to identify all sites of
compression.
PMID- 9646743
TI - Muscle injury in repetitive motion disorders.
AB - Documentation of causality between repetitive motions and musculoskeletal
disorders calls for detailed understanding of the exposure variables and the
corresponding physiologic responses in the biologic tissues. Quantification of
the kinetics in some jobs characterized by repetitive motions is summarized with
the physiologic responses in the muscles. Muscle activity pattern was studied in
different shoulder muscles or muscle parts, and in elbow and wrist flexor
muscles. Activity pattern was dependent on the kinetics of the work requirements.
This holds true for the compound electromyographic signal and for single motor
units. Low threshold motor units have been identified that are recruited
continuously, the so called Cinderella fibers. The physiologic consequences of
prolonged muscle fiber activity are reviewed, revealing mechanisms for the
development of necrotic changes in the muscle, which support the likelihood of
work relatedness for musculoskeletal disorders.
PMID- 9646744
TI - Structure and physiology of joints and their relationship to repetitive strain
injuries.
AB - Joints involved in repetitive strain injuries are diathrodial, that is, two bone
ends with cartilaginous end plates sheathed by a soft envelope of synovium. The
cartilaginous plates, consisting of chondrocytes, ground substance, and at least
seven species of collagen, but mostly Type II, cushion the bone ends during
repeated elastic compression and enable them to slide with minimal friction. The
metabolic needs of the avascular cartilage are met by nutrients and waste
products diffusing through the synovial fluid and into and out of the synovium
and its blood vessels and lymphatics. Synovial nerves give joint position
information. Fat, collagen, and glycosaminoglycans constitute the deformable
synovial sheath. Synovial lining cells synthesize joint lubricants, matrix
molecules, digestive enzymes, and cytokines, and participate in immunologic
processes that can be reparative or degradative especially of cartilage. Heavy
repeated forces applied to the upper and lower extremity joints cause
degenerative changes that can be documented radiographically. Repeated light
loading, such as in computer keyboard use, is evaluated inadequately with current
imaging and clinical techniques. Differences in individual's response to
repetitive loading may be caused by subtle differences in the interaction and
initial conditions of the musculoskeletal structures, including the joint,
involved in repetitive strain injuries.
PMID- 9646745
TI - Risk factors for upper limb disorders. Implications for prevention and treatment.
AB - Epidemiologic studies have revealed several associations between physical work
load factors and some common upper limb disorders. In the treatment of a case of
work related upper limb disorder, modifications of work that are feasible to be
implemented in the field should be done as a first priority. Some case studies
suggest notable effects of ergonomic measures on the occurrence of upper limb
disorders. Economic analyses of individual workplace have indicated that the
investments usually have a short payback period. In work related carpal tunnel
syndrome, the physical demands of the job, especially the force demands of
gripping, should be considered before deciding on surgery, because gripping force
may return slowly after surgery, and may be compromised by the surgical procedure
itself.
PMID- 9646746
TI - Gender and neurogenic variables in tendon biology and repetitive motion
disorders.
AB - The incidence of repetitive motion disorders is increasing. Numerous studies have
indicated that the incidence in females exceeds that in males. Some of the
evidence regarding gender related factors in tendon biology is discussed and new
data related to the regulation of gene expression in an animal model of tendon
overuse, the determination of sex hormone receptors in tendons, and the influence
of pregnancy associated factors on gene expression in four different tendons is
provided. Furthermore, because neurogenic mechanisms may contribute to
inflammatory conditions, new evidence is provided that supports the concept that
neurotransmitters can influence expression of genes that could participate in
such inflammation. By increasing our understanding of the regulation of tendon
cellular and molecular biology, new approaches to preventing disease development
and treatment of existing disease may evolve.
PMID- 9646747
TI - Coping with arm pain in the workplace.
AB - Regional arm pain is a ubiquitous, remittent, and intermittent predicament of
life. There is no evidence that arm use in a fashion that is familiar and usually
comfortable, inside or outside the workplace, increases the incidence of regional
arm pain. Therefore, coping with this morbidity, not avoiding it, is prerequisite
to healthfulness. When one systematically examines the reasons a worker may find
coping prohibitive, task demands are not the common denominator. Psychosocial
factors such as work organization and interpersonal relationships predominate.
PMID- 9646748
TI - Australian repetition strain injury phenomenon.
AB - The industrial upper limb pain epidemic colloquially known as repetition strain
injury rapidly increased in the early 1980s to peak in 1985. Its less precipitous
decline coincided with an awareness that repetition strain injury was a
nonphysical sociopolitical phenomenon and a corresponding loss of the pecuniary
benefits enjoyed by the powerful vested interest groups. Although its
protagonists incorrectly claimed that this was a new disease, the rise and fall
of repetition strain injury followed its historical predecessors including
telegraphists' wrist and writer's cramp. Those affected by this phenomenon, a
clearly defined cohort, were all employees who were highly suggestible and
engaged in menial repetitious tasks with little job satisfaction. These patients
were differentiated from those with genuine work related injuries whose symptoms
are reproducible, with physical signs easily defined, disease identifiable, and
response to physical treatment predictable. Most patients with repetition strain
injury genuinely suffered the symptoms of which they complained and made little
secondary gain relative to the protagonists of repetition strain injury who had a
vested interest. The similarities between Australian repetition strain injury in
the 1980s and American cumulative trauma disorder in the 1990s is compelling.
PMID- 9646749
TI - Workers compensation. Effect of state law on treatment cost and work status.
AB - Workers compensation legislation is regulated at a state level resulting in
different benefits based on the state of employment. The negative effect of
workers compensation on the results of surgical treatment has been established
previously. A comparison of the results of treatment of patients receiving
workers compensation from different states has not been reported. This study
prospectively evaluated the effect of the difference in state workers
compensation laws on the number of postoperative visits, amount of postoperative
therapy, time off from work, and return to work status. The study group consisted
of 275 patients. The results indicated a significant increase in the number of
postoperative visits, amount of therapy, time off from work, and number of
patients who remained out of work in the compensation versus the noncompensation
group. A significant increase in these parameters also was present in the
Pennsylvania compensation group as compared with the New Jersey compensation
group. This study shows that differences in workers compensation benefits have a
significant effect on the results of medical treatment, return to work status,
and the cost of medical care.
PMID- 9646751
TI - Cubital tunnel syndrome pathophysiology.
AB - Cubital tunnel syndrome is the second most common peripheral compression
neuropathy. The unique anatomic relationships of the ulnar nerve at the elbow
place it at risk for injury. Normally with elbow range of motion, the ulnar nerve
is subjected to compression, traction, and frictional forces. As the elbow is
flexed the arcuate ligament elongates producing a decrease in canal volume of
55%. Intraneural and extraneural pressures increase and have been shown to exceed
200 mm Hg with elbow flexion and flexor carpi ulnaris contraction. Because the
ulnar nerve courses behind the elbow axis of rotation, elbow flexion produces
excursion of the nerve proximal and distal to the medial epicondyle. The ulnar
nerve also elongates 4.7 to 8 mm with elbow flexion. Cubital tunnel syndrome may
develop because of various factors including repetitive elbow motion, prolonged
elbow flexion, or direct compression. An understanding of the anatomy and
pathophysiology associated with cubital tunnel syndrome will aid in patient
evaluation and determination of the appropriate treatment.
PMID- 9646750
TI - Carpal tunnel syndrome as a repetitive motion disorder.
AB - The incidence of repetitive motion disorders is increasing and in 1990 comprised
48% of all reported workplace illnesses (up from 18% in 1980). Carpal tunnel
syndrome is the most prevalent disease classified as a repetitive motion
disorder, thus making its prevention and management an occupational health and
safety priority. The clinical picture of carpal tunnel syndrome, pain and
paresthesias on the palmar radial aspect of the hand, often worse at night,
and/or exacerbated by repetitive, forceful use of the hand, is recognized
readily. Carpal tunnel syndrome is a condition of middle aged people and most
middle aged people work. It follows that more often than not carpal tunnel
syndrome occurs in a work-place setting, and the extent to which the work
contributes to the condition is of great interest regarding prevention and
treatment. Some studies find little evidence supporting the concept of carpal
tunnel syndrome as caused by work, whereas others propose that more than half of
cases of carpal tunnel syndrome in workers may be attributed to workplace
factors. It is explored whether the incidence, prevalence, and significance of
carpal tunnel syndrome as a repetitive motion disorder is known.
PMID- 9646752
TI - Impingement syndrome and rotator cuff disease as repetitive motion disorders.
AB - The relationship between repetitive motion and subacromial impingement and
rotator cuff disease is controversial and poorly understood. The potential
etiology is multifactorial and involves patient related factors (age,
supraspinatus outlet anatomy, and preexisting rotator cuff pathology) and worker
related factors (arm position, lifting requirements, numbers of repetitions).
Radiographic and magnetic resonance imaging abnormalities may represent
preexisting disease that could have predisposed the patient to the development of
impingement syndrome, but should be interpreted cautiously within the context of
the remainder of the clinical picture. Treatment often involves temporary or
permanent modifications of the work environment.
PMID- 9646753
TI - Focal dystonia and repetitive motion disorders.
AB - It commonly is observed that focal hand dystonias, such as writer's cramp or
musician's cramp, are associated with repetitive movements, although definitive
proof of a causal relationship is lacking. These focal dystonias are often task
specific, with involuntary muscle contractions occurring only when patients
perform specific acts such as writing or playing a musical instrument.
Physiologic studies show deficiencies in spinal reciprocal inhibition and
abnormalities of central sensory processing and motor output that may be related
to reduced cortical inhibition. Recent studies in primates support the notion
that repetitive motions can induce plasticity changes in the sensory cortex
leading to degradation of topographic representations of the hand, and raise the
possibility that sensory training may be beneficial. Current treatment options
for focal dystonia include botulinum toxin injections, anticholinergics,
baclofen, benzodiazepines, and occupational therapy.
PMID- 9646754
TI - Cumulative trauma disorders and repetitive strain injuries. The future.
AB - Cumulative trauma disorders account for 56% of all occupational injuries.
Currently, occupational injuries affect 15% to 20% of all Americans. The United
States government predicts that by the year 2000, 50% of the American workforce
will have occupational injuries annually and 50 cents of every dollar will be
spent on cumulative trauma disorders. There is common agreement on the need for
reduction of cumulative trauma disorders in the workplace. However, there is
little agreement on the appropriate definition for musculoskeletal pain that
occurs in the workplace, or the ergonomic and epidemiologic model for cumulative
trauma disorders, or on the specific exposure relationships of the individual, by
the job, and occurring in the workplace. The previous treatments for, and the
natural history of, cumulative trauma disorders in other countries gives some
insight into the possible future of cumulative trauma disorders for the United
States. Until research can provide specific dose and exposure relationships for
the individual, prevention remains the best treatment for cumulative trauma
disorders in the workplace.
PMID- 9646755
TI - Debridement arthroplasty for osteoarthritis of the elbow.
AB - For treatment of osteoarthritis of the elbow, the authors use debridement
arthroplasty with a medial or lateral approach. Thirty-eight elbows in 36
patients treated with this procedure were examined. The age of the patients
ranged from 20 to 71 years, with a mean age of 41.7 years. Cubital tunnel
syndrome was present in 16 of the 38 (42%) elbows. The operations were performed
through a lateral approach in four elbows, a lateral approach with medial skin
incision for ulnar nerve neurolysis in 16 elbows, a medial approach in 10 elbows,
and a medial plus a lateral approach in eight elbows. The followup ranged from 2
years to 12.1 years, with an average of 5.9 years. Complete pain relief or
minimal elbow pain was reported in 95% of patients who had surgical treatment.
The average gain in motion was 6 degrees extension and 18 degrees flexion.
Results for the various surgical approaches did not show a statistically
significant difference. Recurrence of bony spurs and ridges was analyzed
additionally in 18 selected patients who could be observed more than 5 years
after surgery (range, 5-12 years). Redevelopment of bony spurs on the coronoid
process and olecranon tip occurred in all 18 patients, but those changes were
graded as mild in 13 (74%) patients and moderate in five (16%) patients and were
accompanied by no pain or slight pain. Elbow arthroplasty as used by the authors
produces stable and reliable results for relief of pain, gains in range of
motion, and the absence of recurrence of significant osteoarthritis.
PMID- 9646756
TI - Patient satisfaction and function after primary and revision total hip
replacement.
AB - This study assessed and compared satisfaction and function before and after total
hip replacement as reported by 531 patients who had primary and revision surgery
and 1087 patients who had primary surgery only. All operations were registered by
the Norwegian Arthroplasty Register during the years 1987 to 1993, with time from
last surgery to followup ranging from 0.6 to 6.4 years. Sixty-one percent of the
patients who underwent revision surgery and 84% of the patients who did not
undergo revision surgery rated their overall satisfaction with the hip implant as
good or very good. With adjustment for primary diagnosis, gender, age,
bilaterality, and time since the primary operation, a substantial benefit of
total hip replacement was observed in both groups with regard to pain, walking
ability, and need of help. However, improvement was less among patients who
underwent revision total hip replacement than among those who did not undergo
revision surgery. A deterioration was seen among patients who underwent revision
surgery with regard to employment status and exercise habits.
PMID- 9646757
TI - Biomechanical effect and clinical application of the hip joint moment reduction
brace.
AB - A new brace, the hip joint moment reduction brace, has been designed and
constructed. The basic construct of the brace incorporates only the thigh, and it
minimally restricts one's activities of daily living. The concept of the brace is
to reduce the frontal plane moment of the applied force against which the
abductor muscle must contract to balance, and this reduction of the frontal plane
moment results in reduction of the abductor muscle force. The brace uses the
mechanism of the ischial weightbearing and lessens the abductor moment by
transmitting load from the ischium through the condyle of the femur. In gait
testing, the maximum ischial load taken up by the brace was 36.9% of the ground
reaction force in the late stance phase, and the integrated electromyogram of the
abductor muscle was reduced by 32.6% during the whole stance phase using this
brace. These findings confirmed a reduction in the frontal plane moment of the
hip joint and the potential for reduction in the load on the hip joint. The hip
joint moment reduction brace is recommended as effective conservative management
of hip disorders, such as coxarthrosis, that are caused or worsened by
biomechanical insufficiency.
PMID- 9646758
TI - Hemispheric titanium porous coated acetabular component without screw fixation.
AB - One hundred fifteen hips in 108 patients with primary total hip arthroplasty
using the anatomic porous replacement hemispheric acetabular component implanted
without adjunctive screw fixation had a mean postoperative followup time of 6
years (range, 5-7.4 years). Clinical evaluation was performed using the Harris
hip score and patient self assessment using a modified Short Form-36
questionnaire. Radiographs were measured for radiolucent lines, polyethylene
wear, osteolysis, migration, and fractures. No acetabular metal shell had been
revised for loosening or was radiographically loose with or without migration
(more than 3 mm) at final followup. Reoperation was done in nine (8%) hips
because of polyethylene insert wear or disassembly. No fracture of the acetabular
bone occurred at the time of surgery or was observed on radiograph. Fixation of
the metal shell was stable, with progressive radiolucent lines observed at final
followup in 2% of the hips. Osteolysis was recorded in one patient with two
acetabular components. The fixation of noncemented hemispheric porous coated
acetabular components is more related to the technique of acetabular bone
preparation and press fit implantation than to whether additional screws or peg
fixation are used. Fixation of this acetabular component without screws at an
average of 6 years after surgery is reproducible and predictable in primary hip
arthroplasty. The design of modular polyethylene inserts has been improved and
should reduce the wear rate of reoperations of the polyethylene insert.
PMID- 9646759
TI - 3- to 11-year followup of occipitocervical fusion for rheumatoid arthritis.
AB - The relief of myelopathy usually is unsatisfactory by a conventional Gallie type
atlantoaxial fusion for patients with rheumatoid arthritis who have irreducible
atlantoaxial dislocation. To accomplish a decompressive laminectomy of the atlas
in the treatment of myelopathy, the authors have been performing a new surgical
procedure since 1985 for occipitocervical fusion using a rectangular rod. The
postoperative outcomes for 25 patients with rheumatoid arthritis were evaluated
clinically and radiographically with a 3- to 11-year (mean, 6.5 years) followup.
A decompressive laminectomy of the atlas accompanied the fusion in 21 of the 25
patients. The incidence of occipital or nuchal pains improved notably in most
cases, and myelopathy was relieved in 12 of 18 (67%) cases, showing an
improvement of more than one level based on Ranawat's criteria. No serious
postoperative complications were seen, except for one case of a failed bone
union. The cumulative survival in patients with myelopathy was 79.4% in the first
5 years after operation and 27.5% at 10 years. Occipitocervical fusion using a
rectangular rod accompanied by a decompressive laminectomy of the atlas can
contribute to the relief of a neurologic deficit in an irreducible atlantoaxial
dislocation in rheumatoid arthritis.
PMID- 9646760
TI - Spontaneous union of a congenital pseudarthrosis of the tibia after Syme
amputation.
AB - A 4-year-old boy with congenital pseudarthrosis of the tibia had two unsuccessful
operative attempts for union. After these procedures the patient had a 6-cm leg
length discrepancy and an equinovalgus foot deformity. Because of these
deformities he underwent Syme amputation at the ankle and was fitted with a total
contact prosthesis. Eight months after the amputation, a solid union was seen
across the pseudarthrosis site, although no attempt was made to achieve union
with internal fixation or bone grafting. The authors think that vertical
alignment of the limb in a total contact prosthesis, along with the compressive
forces of weightbearing, allowed the pseudarthrosis site to heal in the patient.
PMID- 9646761
TI - Intraoperative radiographic assessment of ankle fractures.
AB - This retrospective study was performed to determine whether three or two
radiographic views are necessary for intraoperative evaluation of low energy,
rotational ankle fracture reduction and fixation. Four orthopaedic surgeons
independently reviewed two sets of radiographs of 93 low energy, rotational ankle
fractures treated by open reduction and internal fixation. The reviewers judged
reduction and fixation, without measurement, as if they had been the operating
surgeons. Set 1 consisted of mortise and lateral views and Set 2 consisted of
anteroposterior, mortise, and lateral views. There was a 2-month interval between
the review of Set 1 and Set 2. Intraobserver consistency for Sets 1 and 2 for
reduction ranged from 92% to 98% and consistency for fixation ranged from 85% to
94%. These results underwent statistical testing by calculation of the kappa
value. With a 95% confidence interval, the kappa value for reduction ranged from
0.376 to 0.701; the kappa value for fixation ranged from 0.598 to 0.781. The
interobserver consistency for Sets 1 and 2 also was calculated. The authors
conclude that fracture reduction and fixation can be assessed adequately with
lateral and mortise views. The anteroposterior view can be eliminated from the
standard radiographic protocol, potentially resulting in cost savings.
PMID- 9646762
TI - Two open forearm fractures after airbag deployment during low speed accidents.
AB - Automotive airbags effectively mitigate the impact of vehicular collision by
absorbing and distributing a force that otherwise would be sustained by the
occupants. To be effective, inflation must be instantaneous and sufficient to
provide restraint to a moving body. Deployment of automotive airbags is a violent
event that may cause injury to the occupants of the vehicle. This report
describes two patients with severe, open radius and ulna fractures that were
caused by airbag inflation during low velocity motor vehicle accidents. The
degree of soft tissue injury and bone comminution in these patients was not fully
appreciated until surgery. Orthopaedic surgeons should be aware of the explosive
nature of airbag deployment and realize that the injury may be far greater than
expected from a low energy motor vehicle accident.
PMID- 9646763
TI - Effects of musculoskeletal neoplasms on patient self assessment of health status.
AB - Eighty-five consecutive patients referred to the Musculoskeletal Tumor Service
completed a standardized short form questionnaire to evaluate their health status
and function. Each patient completing the Short Form-36 questionnaire had a
diagnosis of musculoskeletal neoplasm, including benign soft tissue and bone
tumors, malignant soft tissue and bone tumors, and metastatic tumors. The results
of this preliminary study show that the authors' patient population experienced
health status and functional deficits in each of the eight Short Form-36 assessed
domains. Data show that the most severe deficits were experienced by patients who
had diagnoses of bone tumors and malignant tumors. This study shows that the
Short Form-36 is a practical and effective method for documenting perceived
deficits in health status in patients with musculoskeletal tumors. These data
allow the physician to understand the presenting condition from the patient's
perspective. This is an important and often neglected aspect of the overall
assessment of the health of patient on presentation. An understanding of these
deficits is critical for effective planning of treatment and evaluation of
treatment effectiveness.
PMID- 9646764
TI - Biomechanical comparison of antegrade and retrograde nailing of humeral shaft
fracture.
AB - A pair-controlled study was conducted to compare biomechanical properties of
antegrade and retrograde nailing of humeral fractures. First, six paired fresh
anatomic specimen humeri were used to compare the properties of humeri fractured
at the middle to distal diaphyses junction that were nailed from the retrograde
approach with the Humeral Locked nail with those of contralateral intact humeri.
An 18 additional pairs were divided into three equal groups by distal, proximal,
or mid-diaphysis location of a standardized 5-mm bone defect to simulate unstable
fractures. The retrograde and antegrade nailings were performed in each pair in a
random manner. Nail and bone constructs were tested for bending stiffness by
nondestructive three-point bending and for torsional stiffness by destructive
torsional tests. Compared with intact humeri, fractured humeri fixed with nails
had 28.6% posteroanterior and 31.4% mediolateral bending stiffness, 22.5%
torsional stiffness, and 43.3% failure torque. For distal fractures, retrograde
nailing showed significantly more initial stability and higher bending and
torsional stiffness; for proximal fractures, antegrade nailing showed similar
properties. For middle to distal diaphyses junction fractures, retrograde and
antegrade nailing were indistinguishable. The defect created as an entry portal
for retrograde nailing reduced the bone strength only 11.1%. These results
suggest that retrograde nailing, which is less detrimental to shoulder function
than is antegrade nailing, is an acceptable alternative treatment for humeral
shaft fractures. In addition, nailing from the short to the long bone segments
can improve mechanical properties of the fixation construct because of better
nail and bone interface purchase.
PMID- 9646765
TI - Analysis of muscle bioenergetic metabolism in rabbit leg lengthening.
AB - The effect of lengthening on muscle metabolism was measured and correlated to the
percent lengthening at early and late time points. Using the rabbit tibial
lengthening model, the authors examined the effects of lengthening on the
tibialis anterior muscle using phosphorus-31 magnetic resonance spectroscopy.
Thirty-six rabbits were divided into five groups, four groups by percent
lengthening (0%, 15%, 20%, and 25%), with each group divided into subgroups of
early (end distraction) and late (12 weeks after end distraction), and the fifth
group using the opposite untreated leg as control. Several parameters measuring
metabolism of muscle using phosphorus-31 magnetic resonance spectroscopy analysis
were compared. No changes occurred to 15% lengthening, but significant decreases
were measured at 20% and 25% lengthening. After a 25% lengthening, the decreased
metabolism persisted at 12 weeks after distraction, indicating the possibility of
permanent damage. After 20% lengthening, the same parameters improved but never
to normal levels. The authors conclude that lengthening to 15% is safe for
muscle, but 20% to 25% lengthening may result in permanent metabolic damage. The
current study also suggests that phosphorus-31 magnetic resonance spectroscopy
may provide a viable clinical method for evaluating muscle damage during
lengthening.
PMID- 9646766
TI - The effect of translation of the C1-C2 on the spinal canal.
AB - The stability of the atlantoaxial articulation depends fundamentally on the
integrity of the odontoid process and the ligaments. Ligament stability mostly is
maintained by two ligaments: the transverse ligament and the alar, apical
ligaments. Failure of the transverse ligament can result in anterior translation
of the atlas on the axis. The anteroposterior diameter of the ring of the atlas
is approximately 3 cm. The spinal cord and the odontoid process are each
approximately 1 cm in diameter, approximately 1/3 the diameter of the ring.
According to Steel's rule of thirds, the remaining centimeter of free space
allows for some degree of pathologic displacement. The current anatomic study
showed that the space available for the spinal cord was limited. The sagittal
diameter C1-C2 canal is 18.71 +/- 2.88 mm (excluding 10 mm thickness of the dens
and 2.91 +/- 0.69 mm thickness of transverse ligament), with the spinal cord
occupying 7.73 +/- 0.87 mm of the available space. Space available for spinal
cord at the level of the atlas is 3.44 +/- 1.19 mm plus 1.01 +/- 0.20 mm space
anterior to the cord (anterior epidural space) and 5.64 +/- 2.22 mm space
posterior to the cord (posterior epidural space), which is approximately in
agreement with the normal diameter by Steel's rule of thirds.
PMID- 9646767
TI - Fracture healing and callus innervation after peripheral nerve resection in rats.
AB - The effects of femoral and sciatic nerve resection on fracture healing and
innervation of the fracture callus were studied using a stable fracture model. In
34 rats the right tibia was subjected to a standardized closed fracture and
stabilized with a modular intramedullary nail. In half of the animals, resection
of 1 cm of the femoral and sciatic nerves was performed (nerve resection group),
whereas the other animals had sham operations (sham group). To avoid unequal load
bearing between the two groups, all fractured hindlimbs were immobilized in a
plaster of Paris cast. The trial was terminated after 5 weeks of fracture
healing. Callus size was scored radiographically, and bone mineralization was
measured by 85-strontium incorporation. Seven rats from each group had
immunohistochemical examination for neural regeneration and ingrowth. Antisera
for protein gene product 9.5, neurofilaments, neural growth associated protein
43/B-50, calcitonin gene related peptide, and substance P were used. The
mechanical properties of the healing fractures were recorded in a three-point
cantilever bending test. After 5 weeks, the normally innervated, fractured tibias
had regained approximately 50% strength compared with the unfractured side, in
comparison with only 20% in the animals that had nerve resection. Although the
fracture calluses were mechanically weaker, they were significantly larger in the
nerve resection group, indicating defects in tissue composition or organization
rendered by the nerve injury. The mineralization rate, as measured by 85
strontium incorporation, was the same in the two groups. However, the nerve
resection did not provide complete denervation but changed the innervation
pattern of the healing fracture, as the density of sensory nerve fibers
immunostaining for substance P and neurofilaments was less in the group with
femoral and sciatic nerve resection. The results suggest that intact innervation
is essential for normal fracture healing because nerve injury induced a large,
but mechanically insufficient, fracture callus.
PMID- 9646768
TI - Possible mechanism of painful radiculopathy in lumbar disc herniation.
AB - The pathophysiologic mechanisms of painful radiculopathy caused by a herniated
intervertebral disc remain unknown. This study sought to determine whether the
autologous intervertebral disc produces pain related behavior and whether
phospholipase A2 and nitric oxide are involved in the pathophysiologic mechanism
producing the behavior. A rat model, in which autologous intervertebral discs
were implanted on the nerve root in the lumbar spine, was used to measure
hyperalgesia, which is a pain related behavior in the rat. In this experimental
model, autologous nucleus pulposus and anulus fibrosus transplanted to lumbar
nerve roots produced mechanical and thermal hyperalgesia, respectively. Epidural
injection of a selective inhibitor for phospholipase A2 resulted in the
disappearance of hypersensitivity to noxious mechanical stimuli. Thermal
hyperalgesia produced by application of the anulus fibrosus was abated and
abolished by epidural injections of saline and one of the inhibitors for nitric
oxide synthase, respectively. The authors suggest that chemical mediators such as
phospholipase A2 and nitric oxide, induced by extruded or sequestrated
intervertebral discs, are involved in the pathophysiologic mechanisms of painful
radiculopathy in lumbar disc herniations. This study may be useful in attempting
to develop new medical approaches for treatments of lumbar disc herniation.
PMID- 9646769
TI - The Marshall R. Urist Young Investigator Award. Gene expression during autograft
lumbar spine fusion and the effect of bone morphogenetic protein 2.
AB - A prospective animal study of posterolateral lumbar spine arthrodesis was
performed to determine the temporal and spatial pattern of gene expression and to
determine the effect of recombinant human bone morphogenetic protein 2 on the
gene expression pattern of a healing spine fusion mass. In Group 1, 20 adult New
Zealand rabbits underwent L4-L5 posterolateral intertransverse process
arthrodesis using autograft alone. Two rabbits were euthanized at each of the
following points: 0, 2, and 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after
surgery. The same surgical technique was used for 16 rabbits in Group II, except
that the autograft first was soaked in a solution of recombinant human bone
morphogenetic protein 2 before implantation. Ribonucleic acid was extracted from
different regions of the fusion mass at each point and analyzed for expression of
bone and cartilage related genes using reverse transcription polymerase chain
reaction. A reproducible temporal sequence and spatial pattern of gene expression
was found in healing spine fusions. In the central portion of the fusion mass a
temporal lag in gene expression was observed that parallels the lag in healing
within the central zone previously observed in histologic studies. Treatment of
bone graft with recombinant human bone morphogenetic protein 2 resulted in an
increase in the early expression of bone morphogenetic protein 6 which was
associated with expression of higher levels of Type I collagen, osteocalcin, and
other bone related genes. These findings suggest that central nonunion may be
associated with delayed expression of osteoblast related genes in the central
region of the forming fusion mass. The growth factor, recombinant human bone
morphogenetic protein 2, increased the level of bone related gene expression
throughout the fusion mass, eliminated the delay in healing within the central
zone, and may decrease the likelihood of a nonunion.
PMID- 9646770
TI - Shoulder pain in a 26-year-old woman.
PMID- 9646771
TI - Surgical technique of the midvastus arthrotomy.
AB - For more than 25 years most surgeons have used a medial parapatellar surgical
approach for total knee arthroplasty because this technique affords simplicity
and excellent exposure to all compartments of the knee. This article describes
how the midvastus muscle splitting approach achieves surgical exposure equivalent
to that of the standard medial parapatellar approach, while preserving the
integrity of the vastus medialis insertion into the medial border of the
quadriceps tendon. This total knee arthroplasty approach divides the vastus
medialis muscle in the direction of its fibers, as opposed to the traditional
method of splitting the quadriceps tendon above the patella. The limited
disruption of the extensor mechanism improves the rapid restoration of quadriceps
muscle control. In addition, a more stable patellofemoral articulation is
evidenced by a marked reduction in the need for lateral retinacular releases.
PMID- 9646772
TI - [Determination of the onset of stroke. Satellite symposium: "Current Approaches
to the Management of Acute Ischemic Stroke", part of the "6th European Stroke
Conference". Amsterdam, 28 May 1997].
PMID- 9646773
TI - Syndromes of thrombosis and hypercoagulability. Congenital and acquired causes of
thrombosis.
AB - Blood coagulation protein and platelet defects are now known to account for up to
ninety percent of unexplained venous thrombosis and up to seventy percent of
unexplained arterial thrombotic or ischemic events. This article summarizes the
common and uncommon blood protein and platelet defects which should be suspected,
and searched for, in patients with such events. Defining such defects will have
major impact on secondary prevention and duration of antithrombotic therapy in
the afflicted patient and impact on primary prevention for identified family
members in those harboring hereditary defects.
PMID- 9646774
TI - Diagnosis of deep venous thrombosis and pulmonary embolism.
AB - Diagnostic evaluation in the patient with suspected deep vein thrombosis (DVT)
and pulmonary embolism (PE) includes a clear correlation between clinical
probability, test selection and test interpretation. Real-time B-mode ultrasound
with color Doppler remains the imaging technique of choice in suspected DVT. The
ventilation/perfusion (V/Q) lung scan is the preferred diagnostic modality in
suspected PE. The D-dimer assay may be useful in excluding PA. New diagnostic
techniques, including spiral computerized tomography may further modify the
diagnostic algorithm.
PMID- 9646775
TI - Prophylaxis of deep venous thrombosis and pulmonary embolism. Current
recommendations.
AB - Pulmonary embolism is responsible for approximately 150,000 to 200,000 deaths per
year in the United States. Venous thromboembolism usually occurs as a
complication in patients who are sick and hospitalized, but it may also affect
ambulant and otherwise healthy individuals. Many patients who die from pulmonary
embolism succumb suddenly or within 2 hours after the acute event (i.e., before
therapy can be initiated or take effect). Therefore, prevention is the key to
reducing death and morbidity from venous thromboembolism. Effective and safe
prophylactic measures against venous thromboembolism are now available for most
high-risk patients. This article highlights practical approaches to the
prevention of venous thromboembolism.
PMID- 9646776
TI - Treatment of deep venous thrombosis and pulmonary embolism. Current
recommendations.
AB - The therapy of deep venous thrombosis consists of several elements and depends on
the localization, the age and the extent of the thrombus. This article discusses
various types of initial therapy and long-term treatment of venous
thromboembolism and also reviews future perspectives of pharmacological
treatment. The initial treatment regimens comprise thrombolysis, thrombectomy,
inferior vena cava filters and the anticoagulation with either unfractionated
heparin or low molecular weight heparins. Various thrombin-inhibitors have been
tested for initial treatment of thrombosis, however, further investigations of
their efficacy, safety and cost-effectiveness will have to provide firm evidence
on their superiority when compared to unfractionated or low molecular weight
heparins.
PMID- 9646777
TI - Thrombosis and cardiovascular disease.
AB - The early stages of venous thrombosis originate at selective sites of reduced
blood flow in the apices of venous valves. Stagnation of venous flow results in
the formation of a platelet-fibrin thrombus, which serves as the nidus for
thrombus propagation. Stasis alone, however, does not result in thrombosis
necessarily. The presence of activated coagulation factors is essential. The
major predisposing factors to venous thrombus are activation of blood coagulation
and venous stasis. In contrast to venous thrombus formation, vascular
abnormalities are the most important causative factor in arterial thrombosis.
PMID- 9646778
TI - Thrombosis and cerebrovascular disease.
AB - Strokes are heterogeneous not only with respect to their presentation, but more
importantly in terms of the underlying pathology. There are now a number of
choices available for the treatment of ischemic stroke, and the causative
mechanisms responsible for each individual stroke must be considered in choosing
an appropriate form of treatment. This article explores the underlying
pathophysiological mechanisms responsible for the major categories of stroke and
also examines the reasons why strokes worsen or evolve.
PMID- 9646779
TI - Interventional use of plasminogen activators in central nervous system diseases.
AB - Still an experimental approach, the direct intra-arterial infusion of plasminogen
activators in the setting of acute thrombotic stroke has received impetus from
successful clinical trials of intravenous infusion therapy. Direct therapy,
employing catheter delivery, has successfully produced evidence of recanalization
in carotid artery territory and vertebrobasilar artery territory thrombotic
occlusions. One very recent prospective randomized study has demonstrated the
success and limitations of this approach. Attention to safety concerns will be
important to the future success of direct intra-arterial delivery of plasminogen
activators in acute thrombotic stroke.
PMID- 9646780
TI - Antithrombin agents as anticoagulants and antithrombotics. Implications in drug
development.
AB - Synthetic and recombinant thrombin inhibitors have undergone several clinical
evaluations for thrombotic and cardiovascular indications. While the initial
trials were focused in coronary indications, more recently, these agents are also
developed for the prophylaxis and therapeutic management of thromboembolic
disorders. Hirudin, PEG-hirudin and argatroban are in advanced clinical
development. Recombinant hirudin has been approved in Europe as a substitute
anticoagulant for the management of HIT patients. Several additional clinical
trials are currently carried out to demonstrate the usefulness of these agents in
thrombotic and cardiovascular indications. Despite these developments such issues
as dosage optimization, laboratory monitoring, neutralization and drug
interactions require additional studies for the optimal development of these
drugs.
PMID- 9646781
TI - Unfractionated and low-molecular-weight heparin. Comparisons and current
recommendations.
AB - Intravenous heparin followed by warfarin has been the classical anticoagulant
therapy of acute venous thromboembolism for the past 30 years. In recent years a
number of low-molecular-weight heparins have become available for clinical
trials. These agents have a number of advantages over unfractionated heparin and
are now being used internationally for the prevention and treatment of venous
thromboembolism. Low-molecular-weight heparin will undoubtedly replace
intravenous unfractionated heparin not only in the treatment of venous
thromboembolism but in other conditions where heparin therapy is indicated.
Whether or not the low-molecular-weight heparins can decrease or eliminate some
of the complications of unfractionated heparin will depend on the outcome of
future clinical trials.
PMID- 9646782
TI - Current recommendations for warfarin therapy. Use and monitoring.
AB - With the aging population, the use of warfarin will continue to increase. The
introduction of new thromboplastins with International Sensitivity Indices (ISI)
of 1.0 to 1.5 has improved the efficacy of monitoring warfarin therapy with the
prothrombin time (PT). Increasingly, outpatient oral anticoagulant clinics and
home testing are the sites for PT monitoring.
PMID- 9646783
TI - International consensus recommendations. Summary statement and additional
suggested guidelines. European Consensus Conference, November 1991. American
College of Chest Physicians consensus statement of 1995. International Consensus
Statement, 1997.
AB - Since the NIH Consensus Conference in 1986, the developments in the field of
prevention and treatment of venous thromboembolism were mainly characterized by a
more specific and extended use of new prophylactic agents such as low-molecular
weight heparins as well as the perception that out-patients may be at risk for
thromboembolic complications, too. Therefore, in 1991 and 1995, consensus
conferences were held in Europe and North America in order to analyze the risk
constellation of various patient populations and to give recommendations for
primary prophylaxis and treatment of thromboembolic complications. The most
recent, the 1997 International Consensus Recommendations are also discussed.
PMID- 9646784
TI - Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side
effects of heparin therapy.
AB - Although several new anticoagulant drugs are in development, heparin remains the
drug of choice for most anticoagulation needs. The clinical effects of heparin
are meritorious, but side effects do exist. Important untoward effects of heparin
therapy including heparin-induced thrombocytopenia, heparin-associated
osteoporosis, eosinophilia, skin reactions, allergic reactions other than
thrombocytopenia and alopecia will be discussed in this article.
PMID- 9646785
TI - Predictions for nuclear medicine in the next decade.
PMID- 9646786
TI - The genesis of modern science: contributions of scientific societies and
scientific journals.
PMID- 9646787
TI - Imaging-guided gene therapy in the central nervous system.
PMID- 9646788
TI - U.S. radiologists' workload in 1995-1996 and trends since 1991-1992.
AB - PURPOSE: To measure U.S. radiologists' workload and the variation and trends in
workload. MATERIALS AND METHODS: A stratified, random sample of 794 radiology
practice groups were surveyed about hiring and workload in 1996; 78% responded.
Responses were weighted to represent all U.S. radiologists. Types of procedures
performed in Medicare patients in 1991 and 1995 were analyzed. RESULTS: In 1995
1996, the average workload per full-time equivalent diagnostic radiologist was
11,600 procedures +/- 200 (standard error) annually, an apparent (but not
statistically significant) 5% increase from 4 years earlier. Average relative
value units per Medicare procedure increased by 8%, due to the increasing role of
magnetic resonance imaging, computed tomography, and interventional radiology.
The annual average number of procedures varied substantially by group type (e.g.,
13,200 procedures +/- 500 in groups of two to four radiologists vs 10,300 +/- 300
in groups of 11 or more radiologists). Within any group type, radiologists at the
75th percentile in terms of workload typically performed at least 50% more
procedures than did radiologists at the 25th percentile. CONCLUSION: Given the
large variability in the annual number of procedures within and across group
types, averages should not be taken as norms. Contrary to concerns about a
possible surplus of radiologists, the workload per radiologist has increased
substantially in the past few years.
PMID- 9646789
TI - Kawasaki disease: a review.
PMID- 9646790
TI - US of the painful hip in childhood: diagnostic value of cartilage thickening and
muscle atrophy in the detection of Perthes disease.
AB - PURPOSE: To evaluate the combined use of several ultrasonographic (US) criteria
in the detection of Perthes disease. MATERIALS AND METHODS: In a prospective
study, 144 consecutive children with a painful hip underwent US. The thicknesses
of the (a) anterior recess of the joint capsule, (b) cartilage of the femoral
head, and (c) quadriceps muscle were assessed. Sixty-eight children with no
symptoms, the control group, were also examined. RESULTS: The final diagnosis was
transient synovitis (n = 58), Perthes disease (n = 21), slipped capital femoral
epiphysis (SCFE; n = 5), or miscellaneous (n = 6). Fifty-four patients had no US
or radiographic abnormalities, and symptoms disappeared during follow-up. The
anterior recess in patients with transient synovitis was significantly wider than
that in the other patients and control subjects (P < .001). Patients with Perthes
disease showed significant cartilage thickening in the symptomatic hip compared
with the other patients and control subjects (P < .001). Patients with Perthes
disease and patients with SCFE showed significant atrophy of the ipsilateral
quadriceps muscle compared with all other groups (P < .001). The combined use of
these US criteria for the diagnosis of Perthes disease resulted in a positive
predictive value of 95%, a negative predictive value of 95%, a sensitivity of
71%, and a specificity of 99%. CONCLUSION: The combination of several US criteria
increases the diagnostic value of US of the painful hip in patients with Perthes
disease.
PMID- 9646791
TI - Hip joint fluid: detection and distribution at MR imaging and US with cadaveric
correlation.
AB - PURPOSE: To define the magnetic resonance (MR) imaging appearance of a hip
effusion. MATERIALS AND METHODS: Fifty-two asymptomatic hips in 26 volunteers
aged 20-37 years and five fractured hips were imaged at 1.5 T with T2-weighting
in three planes. Images were computer digitized and analyzed for hip fluid volume
and visually assessed for the presence and width of fluid pockets (in
millimeters) seen in the acetabular notch; recesses anterior, posterior, and
lateral to the femoral head; and recesses anterior, posterior, and medial to the
femoral neck. Cadaveric hips were also injected with graduated amounts of saline
(1-20 mL), and sequential MR and ultrasound images were obtained. RESULTS:
Computer analysis yielded an average fluid volume of 2.7 mL (range, 0.7-5.6 mL)
in asymptomatic and 6.1 mL (range, 1.7-11.6 mL) in symptomatic hips. The mean
difference between the right and left hips was 0.8 mL (range, 0.0-2.9 mL).
Discrete fluid pockets, sometimes measuring greater than 5 mm in width, were
commonly seen in asymptomatic hips. Distention of the capsule by at least 5 mm
along the length of the femoral neck was almost always seen after injection of 5
mL of saline and was consistently seen after injection of 10 mL of saline into
cadaveric hips. CONCLUSION: Fluid adjacent to the entire length of the femoral
neck, measuring at least 5 mm in width, is compatible with a joint effusion.
PMID- 9646792
TI - Quantitative MR imaging evaluation of chondropathy in osteoarthritic knees.
AB - PURPOSE: To determine the validity and the reliability of T1-weighted three
dimensional gradient-echo magnetic resonance (MR) imaging for quantification of
articular cartilage abnormalities of osteoarthritic knees. MATERIALS AND METHODS:
Forty-three patients (mean age, 63 years) with knee osteoarthritis (American
College of Rheumatology criteria) of the medial tibiofemoral compartment
underwent a prospective, cross-sectional study. Knees were examined with a T1
weighted three-dimensional gradient-echo sequence (1.4-mm contiguous sections),
with use of a 0.2-T dedicated MR unit, before arthroscopic exploration. The
tibiofemoral articular cartilage abnormalities were quantified blindly on both
the MR and arthroscopic images with the French Society of Arthroscopy (SFA) score
(0-100) and grading scheme (five grades). RESULTS: There was a statistically
significant correlation between the SFA-arthroscopic score and the SFA-MR score
(r = .83) and between the SFA-arthroscopic grade and the SFA-MR grade (weighted
kappa = 0.84). The deepest cartilage lesions graded with arthroscopy and MR
imaging showed correlation in the medial femoral condyle (weighted kappa = 0.83)
and in the medial tibial plateau (weighted kappa = 0.84). The intraobserver
reliability of the SFA-MR score was higher (r = .94) than the interobserver
reliability (r = .80). CONCLUSION: Quantification of chondropathy with MR imaging
is feasible and well correlated with anatomic cartilage breakdown.
PMID- 9646793
TI - Evaluation of patellar cartilage in cadavers with a low-field-strength extremity
only magnet: comparison of MR imaging sequences, with macroscopic findings as the
standard.
AB - PURPOSE: To assess a low-field-strength extremity-only magnet in the evaluation
of patellar cartilage abnormalities. MATERIALS AND METHODS: Four regions in each
of 10 patellae from cadavers were examined in the transaxial plane with a 0.2-T
extremity-only magnet and the following sequences: T1-weighted spin echo, proton
density- and T2-weighted turbo spin echo, short inversion time inversion
recovery, and two- and three-dimensional gradient echo with and without
magnetization transfer contrast subtraction. Lesions depicted with MR imaging and
seen in anatomic sections of the patellae were classified according to a modified
standardized arthroscopic grading system. MR imaging and pathologic correlation
was then analyzed. RESULTS: On the basis of macroscopic findings, 14 of 40
cartilage regions were found to be intact, grade 2A lesions were present in eight
regions, grade 2B lesions in eight, and grade 3 lesions in 10. For the various MR
imaging techniques, sensitivity was 25%-62% for grade 2A lesions, 50%-75% for
grade 2B lesions, and 60%-90% for grade 3 lesions. Specificity was 81%-97% for
grades 2A and 2B lesions, and 80%-97% for grade 3 lesions. Accuracy was 75%-82%
for grade 2A lesions, 75%-92% for grade 2B lesions, and 80%-92% for grade 3
lesions. CONCLUSION: High-grade cartilaginous lesions can be evaluated reliably
with low-field-strength MR imaging by using a combination of imaging sequences.
PMID- 9646794
TI - MR imaging of gene delivery to the central nervous system with an artificial
vector.
AB - PURPOSE: To determine whether gene delivery by means of a synthetic no viral DNA
delivery system that is capable of gene transfer can be mapped with magnetic
resonance (MR) imaging. MATERIALS AND METHODS: The DNA delivery system consisted
of aminated (poly-L-lysine-conjugated) dextran chains anchored together with a
central superparamagnetic core. Three different types of constructs were
synthesized that differed in their amino content and, thus, DNA-loading capacity.
The model plasmid consisted of complementary DNA encoding for humanized green
fluorescent protein. Constructs were tested in cell culture and in vivo in a rat
model. RESULTS: All three constructs were capable of transfecting human cells in
culture with transfection efficiencies ranging from 0.3% to 4.1%, which is
similar to that of diethylaminoethyl-dextran. MR imaging experiments showed that
DNA constructs induced signal intensity changes that co-localized with phosphorus
33-labeled plasmid distribution at autoradiography. After injection of the
constructs into the corpus callosum of rats, weak green fluorescent protein
expression of neuronal and glial cells could be detected at immunohistologic
examination. CONCLUSION: Dextran-based nonviral DNA delivery systems are capable
of transfecting cells and can be visualized with MR imaging.
PMID- 9646795
TI - Excitotoxin-induced cerebral hyperemia in newborn piglets: regional cerebral
blood flow mapping with contrast-enhanced power Doppler US.
AB - PURPOSE: To create regional cerebral blood flow maps with contrast material
enhanced power Doppler ultrasound (US). MATERIALS AND METHODS: In six
anesthetized newborn piglets, cerebral hyperemia was induced after intrastriatal
injection of 5 mumol of N-methyl-D-aspartic acid. Coronal power Doppler US was
performed with a microbubble-based contrast agent, and cerebral blood flow was
determined before and at 15, 30, and 60 minutes after injection. Images were
digitized and analyzed for changes in mean pixel intensity. A bolus injection
curve was constructed by plotting mean pixel intensity versus time, and the area
under this normalized curve was compared with cerebral blood flow. RESULTS:
Hemispheric cerebral blood flow increased from 40 mL/min/100 g +/- 1 (mean +/-
standard error) to 90 +/- 12, 86 +/- 8, and 85 +/- 12 at 15, 30, and 60 minutes
after injection, respectively (P < .0001 [analysis of variance]). Hemispheric
mean pixel intensity at peak contrast also increased from 69 units +/- 5 to 120
+/- 4, 112 +/- 6, and 98 +/- 13 at 15, 30, and 60 minutes after injection,
respectively (P < .003). The area under the normalized curve correlated well with
changes in hemispheric and striatal cerebral blood flow (r = .73, P = .0001; r =
.62, P = .0001, respectively). CONCLUSION: In the newborn brain, regional blood
flow maps can be created accurately with contrast-enhanced power Doppler US.
PMID- 9646796
TI - Intraoperative assessment of microsurgery with three-dimensional optical
coherence tomography.
AB - PURPOSE: To evaluate three-dimensional optical coherence tomography (OCT) for use
in the assessment of the microsurgical anastomoses of vessels and nerves.
MATERIALS AND METHODS: OCT is an optical analogue of ultrasonography and is
capable of imaging nontransparent biologic tissue by detecting backscattered
infrared light. Cross-sectional in vitro images of rabbit and human vessels and
nerves were obtained in as little as 125 msec at 10-micron resolution by using a
solid-state laser as a light source. A surgical microscope was integrated with
OCT to perform simultaneous imaging with en face visualization. Cross-sectional
images were assembled to produce three-dimensional reconstructions of
microsurgical specimens. RESULTS: Three-dimensional OCT reconstructions depicted
the structure within an arterial anastomosis and helped identify sites of luminal
obstruction. The longitudinal spatial orientation of individual nerve fascicles
was tracked in three dimensions to identify changes in position. In vitro human
arteries and nerves embedded in highly scattering tissue and not visible at
microscopy were located and imaged with OCT at eight frames per second.
CONCLUSION: The three-dimensional, micrometer-scale, diagnostic imaging
capabilities of OCT permit rapid feedback for assessment of microsurgical
procedures. OCT technology can be readily integrated with surgical microscopes
and has potential for intraoperative monitoring to improve patient outcome.
PMID- 9646797
TI - Myelolipoma: CT and pathologic features.
AB - PURPOSE: To correlate clinical and pathologic patterns of myelolipoma with the
computed tomographic (CT) appearance. MATERIALS AND METHODS: All cases of
myelolipoma accessioned by the Armed Forces Institute of Pathology from 1981
through 1997 were reviewed. CT images were scored for the location and size of
each myelolipoma and the presence of calcification, hemorrhage, fat, and
pseudocapsule. Pathologic findings for the pattern of fat and bone marrow
elements were correlated with CT findings. RESULTS: In 74 patients, 86
myelolipomas were found, of which 72 were in an adrenal gland (eight were
bilateral), and 14 extra-adrenal masses were found in 10 patients. Four
clinicopathologic patterns emerged: (a) isolated adrenal myelolipoma in 37
patients (fat evident at CT, no other disorders present); (b) myelolipoma with
hemorrhage in nine patients (imaging features similar to those of isolated
adrenal myelolipomas but larger [mean diameter, 14.2 vs 9.9 cm; P = .01]; (c)
extra-adrenal myelolipoma in 10 patients (imaging findings similar to those of
adrenal myelolipomas, found most often in the retroperitoneum); and (d)
myelolipomatous foci within other adrenal pathologic conditions in 18 patients
(smaller, lower fat content, more heavily calcified). CONCLUSION: Myelolipomas
are adrenal or extra-adrenal masses, with hemorrhage more common in larger
lesions (diameter, > 10 cm). The CT appearance of myelolipomatous foci, which can
be found within other pathologic adrenal conditions, is different from that of
isolated adrenal myelolipomas.
PMID- 9646798
TI - Ureterolithiasis: can clinical outcome be predicted with unenhanced helical CT?
AB - PURPOSE: To evaluate the use of helical computed tomography (CT) without contrast
material enhancement for prediction of a favorable outcome in ureterolithiasis.
MATERIALS AND METHODS: CT studies were reviewed in 69 patients with a single
ureteral stone not located at the ureteropelvic junction. CT findings (tissue rim
sign, hydronephrosis, perinephric fat stranding, perinephric fluid collections,
and thickening of renal fascia) were graded on a scale of 0-3. Stone diameter and
renal parenchymal enlargement were also measured. RESULTS: Twenty-two patients
had spontaneous passage, 12 did not respond to conservative treatment, and 35
were lost to follow-up. When the latter 35 patients were excluded, perinephric
fat stranding (P = .044) and perinephric fluid collections (P = .021) were graded
significantly higher in patients with spontaneous stone passage. Mean stone
diameter was significantly larger (P < .001) in patients in whom conservative
treatment failed (mean, 7.8 mm) than in patients with spontaneous stone passage
(mean, 2.9 mm). The presence of a tissue rim sign and the grade of
hydronephrosis, renal fascial thickening, and renal parenchymal enlargement were
not significantly different between the two groups. CONCLUSION: In addition to
stone size, the degree of perinephric fat stranding and the presence of
perinephric fluid collections are useful ancillary signs for help in predicting
the likelihood of stone passage.
PMID- 9646799
TI - Benign and malignant ovarian masses: selection of the most discriminating gray
scale and Doppler sonographic features.
AB - PURPOSE: To determine the gray-scale and Doppler sonographic features that best
enable discrimination between malignant and benign ovarian masses and develop a
scoring system for accurate diagnosis with these features. MATERIALS AND METHODS:
Gray-scale and Doppler sonographic features of 211 adnexal masses were correlated
with the final diagnosis; the most discriminating features for malignancy were
selected with stepwise logistic regression. RESULTS: Twenty-eight masses were
malignant and 183 benign. All masses with a markedly hyperechoic solid component
or no solid component were benign. For masses with a nonhyperechoic solid
component, additional features that allowed statistically significant
discrimination of benignity from malignancy were, in decreasing order of
importance, (a) location of flow at conventional color Doppler imaging, (b)
amount of free intraperitoneal fluid, and (c) presence and thickness of
septations. A scoring formula that made use of values based on the logistic
regression equation had an area under the receiver operating characteristic curve
of 0.98 +/- 0.01. The cutoff score with the highest accuracy had a sensitivity of
93% and specificity of 93%. CONCLUSION: A solid component is the most
statistically significant predictor of a malignant ovarian mass. A multiparameter
scoring system that uses three gray-scale and one Doppler feature, developed by
means of stepwise logistic regression, has high sensitivity and specificity for
predicting malignancy.
PMID- 9646800
TI - Deep pelvic abscesses: transperineal US-guided drainage.
AB - PURPOSE: To examine the efficacy of transperineal sonographically guided drainage
of deep pelvic abscesses. MATERIALS AND METHODS: Twelve drainage procedures were
performed in 11 adults with symptoms of infection and cross-sectional images
demonstrating a deep pelvic abscess. Eight patients had recently undergone
abdominoperineal resection, seven of whom underwent preoperative radiation
therapy. Two had chronic osteomyelitis with adjacent fluid collections, and one
developed an infected hematoma after trauma. With ultrasound (US) guidance for
initial access, catheters were placed for drainage in 11 procedures. One patient
was treated with aspiration alone. Patients underwent clinical follow-up and
subsequent imaging as necessary. RESULTS: Transperineal needle placement was
successful in 12 of 12 patients (100%). In procedures that required catheter
placement, 10 of 11 placements (91%) were achieved with the transperineal
approach. One patient required fluoroscopic transvaginal catheter placement after
opacification of the collection transperineally. Catheter drainage was maintained
for 2-146 days (mean, 40 days; median, 21 days). Clinical success was achieved in
nine of 10 patients (90%) by means of transperineal drainage. There were no
complications, although premature catheter removal occurred in two patients.
CONCLUSION: US-guided transperineal abscess drainage may be successfully
performed in patients who cannot undergo conventional transabdominal,
transvaginal, or transrectal catheter drainage.
PMID- 9646801
TI - Lymphadenopathy: differentiation of benign from malignant disease--color Doppler
US assessment of intranodal angioarchitecture.
AB - PURPOSE: To differentiate reactive from malignant lymphadenopathy by using color
Doppler ultrasonographic (US) findings of intranodal blood vessels. MATERIALS AND
METHODS: Color Doppler US was performed in 117 lymph nodes in 100 consecutive
patients before performance of surgical biopsy (47 nodes), neck dissection (62
nodes), or high-speed core biopsy (eight nodes). The presence of malignant
changes in intranodal angioarchitecture (focal perfusion defects, aberrant course
of central vessels, displacement of intranodal vessels, subcapsular vessels) was
evaluated in each node. Inter- and intraobserver variability were evaluated.
RESULTS: Histopathologic examination demonstrated 48 reactive lymph nodes
(longest diameter +/- standard deviation, 13.5 mm +/- 6.0), 56 nodal metastases
(longest diameter, 19.2 mm +/- 8.8), 12 malignant lymphomas (longest diameter,
23.2 mm +/- 10.5), and one node infiltrated by Langerhans cell histiocytosis. At
color Doppler US, 103 (88%) nodes were classified correctly, with a specificity
of 77% and a sensitivity of 96%. Reproducibility was 90%-96% (kappa = 0.79-0.91,
P < .001). CONCLUSION: Color Doppler US is a reliable and reproducible method for
help in the differentiation between reactive and malignant alterations of
superficial lymph nodes by using findings of intranodal angioarchitecture.
PMID- 9646802
TI - Head trauma: CT scan interpretation by radiology residents versus staff
radiologists.
AB - PURPOSE: To determine the rate and clinical outcome of discrepancies in
interpretation by radiology residents and staff neuroradiologists of
posttraumatic cranial computed tomographic (CT) scans. MATERIALS AND METHODS:
Prospective evaluation was performed for 419 consecutive emergency posttraumatic
cranial CT studies that had been interpreted by radiology residents on call over
a 16-month period. Discrepancies between the interpretations made by residents
and those made by staff radiologists were divided into two groups: failure to
recognize an abnormality (false-negative finding) and interpretation of normal as
abnormal (false-positive finding). Discrepancies were considered major if they
could affect patient care in the emergency setting and minor if they could not.
RESULTS: Major and minor discrepancies were 1.7% and 2.6%, respectively, among
interpretations made by residents and those by staff radiologists. Major
discrepancies were four subdural hematomas, one pneumocephalus, one hemorrhagic
contusion, and one subarachnoid hemorrhage. Minor discrepancies included six
skull and five facial fractures. The discrepancy rate was statistically
significantly higher (12.2%) when CT findings were abnormal than when they were
normal (1.5%). No change in treatment was attributed to the delay in diagnosis.
CONCLUSION: A low discrepancy rate was found between interpretations made by
radiology residents and those made by staff neuroradiologists of posttraumatic
cranial CT scans. There were no adverse clinical outcomes.
PMID- 9646803
TI - Small, patent cerebral aneurysms: atypical appearances at 1.5-T MR imaging.
AB - PURPOSE: To determine the frequency and characteristics of small cerebral
aneurysms with atypical appearances on magnetic resonance (MR) images. MATERIALS
AND METHODS: MR imaging studies (n = 117) obtained at 1.5 T of small aneurysms (<
1 cm diameter) were prospectively and retrospectively analyzed. Signal intensity
characteristics and gadolinium-enhancement patterns in 84 aneurysms (62 patients)
were evaluated. The patency of all aneurysms was confirmed at angiography or at
the time of surgery. RESULTS: A characteristic signal void was seen on 62 (53%)
of 117 studies. On the remaining 55 (47%) studies, aneurysms had atypical signal
intensity that was isointense, heterogeneous, or hyperintense. Contrast-enhanced
aneurysms were seen on 27 (53%) of 51 gadolinium-enhanced studies. CONCLUSION:
Atypical MR imaging characteristics were seen in roughly half of cases. These
atypical-appearing aneurysms may erroneously be considered to be thrombosed or be
mistaken for other common lesions such as small tumors and be dismissed as
nonvascular.
PMID- 9646804
TI - Guillain-Barre syndrome: MR imaging findings of the spine in eight patients.
AB - PURPOSE: To evaluate magnetic resonance (MR) imaging findings of the spine in
patients with Guillain-Barre syndrome. MATERIALS AND METHODS: MR imaging findings
in eight patients (three male, five female; age range, 2-47 years) with Guillain
Barre syndrome were retrospectively reviewed. Guillain-Barre syndrome was
diagnosed mainly on the basis of symptoms and also on the basis of supportive
ancillary data, such as the results cerebrospinal fluid analysis and
electrophysiologic evaluation. In addition, follow-up MR imaging was performed in
three patients, who had slight clinical improvement. RESULTS: All patients had
thickening of the intrathecal spinal nerve roots and cauda equina, with varying
degrees of enhancement on gadolinium-enhanced axial T1-weighted images. Two
enhancement patterns were noted. One was enhancement of both the anterior and
posterior spinal nerve roots (n = 2); the other was enhancement of the anterior
spinal nerve roots only (n = 6). Follow-up MR imaging in the three patients with
slight improvement of symptoms revealed that the thickening and the degree of
enhancement of the spinal nerve roots were diminished. CONCLUSION: Although the
enhancement of the intrathecal spinal nerve roots is not specific to Guillain
Barre syndrome and can be seen in neoplasia and other inflammatory processes, the
enhancement of only the anterior spinal nerve roots is strongly suggestive of
Guillain-Barre syndrome.
PMID- 9646805
TI - The sugarcoating sign.
PMID- 9646806
TI - Hypocalcemic stimulation and nonselective venous sampling for localizing
parathyroid adenomas: work in progress.
AB - PURPOSE: To evaluate whether the release of parathyroid hormone (PTH) from
parathyroid tumors during selective parathyroid arteriography can help localize
the tumors. MATERIALS AND METHODS: In 20 patients (six men, 14 women; age range,
24-72 years) with parathyroid tumors undergoing parathyroid arteriography after
failed surgery, serial measurements of PTH were obtained during selective
arteriography with nonionic contrast material. PTH levels were measured in the
superior vena cava (SVC) before and at varying times from 20 to 120 seconds after
arteriography. RESULTS: A 1.4-fold increase in the PTH level of the
postarteriographic SVC samples enabled correct prediction of the site of adenoma
in 13 of the 20 patients (65%). Of nine patients with positive arteriograms,
eight had positive results of postarteriographic sampling. Of 11 patients with
negative arteriograms, five had positive results of postarteriographic sampling.
CONCLUSION: Sampling the SVC for PTH gradients after selective parathyroid
arteriography correctly indicated the site of the adenoma in 13 of 20 patients
(65%).
PMID- 9646807
TI - Dual-helical CT for detecting aortic atheromas as a source of stroke: comparison
with transesophageal echocardiography.
AB - PURPOSE: To investigate whether unenhanced dual-helical computed tomography (CT)
is useful in the rapid, noninvasive detection of protruding aortic atheromas.
MATERIALS AND METHODS: Thirty-two consecutive patients at least 50 years of age
who had recent ischemic stroke, systemic emboli, or both, underwent
transesophageal echocardiography (TEE) and unenhanced dual-helical CT with thin
sections (section thickness, 3.2 mm; reconstruction increment, 1.5 mm). RESULTS:
TEE demonstrated protruding aortic atheromas 15 patients (47%); dual-helical CT
depicted protruding aortic atheromas in 13 of those 15 patients (87%). Of the 17
patients without a protruding aortic atheroma at TEE, dual-helical CT helped
confirm the absence in 14 (82%). Dual-helical CT yielded a sensitivity of 87%, a
specificity of 82%, and an overall accuracy of 84%. Thirty-six protruding plaques
were detected with TEE, of which 34 (94%) were correctly identified with dual
helical CT. Of those 34 plaques, 27 (79%) contained variable amounts of calcium
and seven (21%) showed hypoattenuation suggestive of soft plaques and thrombi. In
six patients, dual-helical CT depicted a protruding aortic atheroma between the
distal ascending aorta and the proximal arch; these plaques were not included in
the comparative statistics and were analyzed separately. CONCLUSION: Unenhanced
dual-helical CT with thin sections appears to be useful for the rapid,
noninvasive detection of a protruding aortic atheroma, especially in areas not
clearly visualized with TEE.
PMID- 9646808
TI - Percutaneous drainage of fluid collections in the extremities.
AB - PURPOSE: To analyze the results of percutaneous drainage of fluid collections in
the extremities. MATERIALS AND METHODS: From 1990-1997, 28 patients aged 14-90
years underwent percutaneous drainage of 33 fluid collections in the extremities;
two patients underwent multiple drainages. Fluid collections were in the hip
groin area (n = 16), thighs (n = 6), buttocks (n = 6), knees (n = 3), calf (n =
1), and axilla (n = 1). Three intraarticular collections were included. The
patients who had undergone prior procedures were eight who had undergone surgical
drainage, 10 who had undergone needle aspiration, and one who had undergone
surgical debridement. The two most common guidance methods of catheter placement
were ultrasound localization and fluoroscopy. RESULTS: The average drainage
duration was 18.2 days (range, 1-93 days). The estimated cavity sizes were 4-733
cm3. Purulent fluid was drained in 13 patients. Staphylococcus aureus was the
most commonly identified organism (n = 9). Nine patients had postoperative
lymphoceles; five of these patients underwent sclerotherapy. Two (7%) patients
had two complications, one of which was major. Failure occurred in four (16%) of
25 patients; two needed repeat drainage for recurrence, and two needed subsequent
surgery. Success could not be determined in three patients who were lost to
follow-up. CONCLUSION: Percutaneous drainage of fluid collections in the
extremities is an effective alternative to open-incision drainage in inpatients
and outpatients.
PMID- 9646809
TI - Coronary artery stenoses: assessment with contrast-enhanced electron-beam CT and
axial reconstructions.
AB - PURPOSE: To evaluate the usefulness of electron-beam computed tomography (CT) for
identification of coronary artery stenoses. MATERIALS AND METHODS: Coronary
angiography and contrast material-enhanced, electrocardiographically triggered
electron-beam CT of the heart were performed in 23 patients. With axial CT images
and axial maximum intensity projection reconstructions, the coronary arteries
were assessed by two observers blinded to the results of angiography. RESULTS:
Cardiac motion artifact (unsharpness) precluded evaluation of the right coronary
artery (RCA) in six subjects and the left circumflex coronary artery (LCX) in one
patient. With the vessels degraded by motion artifact eliminated from analysis,
overall sensitivity of electron-beam CT for hemodynamically significant stenoses
was 88%, and specificity was 79%. In the left anterior descending coronary artery
(LAD), sensitivity was 93% and specificity was 63%; in the LCX, sensitivity was
100% and specificity was 67%; and in the RCA, sensitivity was 67% and specificity
was 77%. The presence of coronary artery calcification did not have an effect on
sensitivity for stenoses, but it did decrease specificity. CONCLUSION: Electron
beam CT angiography can depict hemodynamically significant stenoses in the LAD
and LCX with a sensitivity of more than 90%. The presence of coronary artery
calcification resulted in decreased specificity but no appreciable change in
sensitivity.
PMID- 9646810
TI - Brachytherapy for prophylaxis of restenosis after long-segment femoropopliteal
angioplasty: pilot study.
AB - PURPOSE: To evaluate in a pilot study the feasibility and efficacy of
endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal
percutaneous transluminal angioplasty (PTA) without stent implantation in a group
of patients with a high risk of restenosis. MATERIALS AND METHODS: Ten patients
(six women, four men; mean age, 68 years) with long-segment (mean length, 16 cm;
range, 9-22 cm) restenosis underwent PTA followed by endovascular irradiation
with high-dose-rate afterloading of an iridium-192 rod. A dose of 12 Gy was
targeted to the inner intimal layer of the vessel. Follow-up examinations until
12 months after PTA included measurement of the ankle-brachial index, color
duplex ultrasonography (US) with calculation of the peak velocity ratio, and
intraarterial angiography when recurrence was suspected. RESULTS: Irradiation was
technically feasible in all patients without complications. In six patients, the
dilated and irradiated segment remained widely patent at color US, with
corresponding excellent hemodynamic and clinical results after 12 months. In four
patients, clinical and laboratory findings indicated recurrence and arteriography
demonstrated restenosis with a diameter reduction of 60%, 70%, 80%, or 90%.
CONCLUSION: Considering the negative selection of patients with a high risk of
restenosis, the results of our pilot study are promising concerning the
possibility of reduction of restenosis by means of endovascular brachytherapy
after long-segment femoropopliteal PTA without stent implantation. The value of
this approach should now be determined definitively in randomized trials.
PMID- 9646811
TI - Bronchial carcinoid tumors: importance of prognostic factors that influence
patterns of recurrence and overall survival.
AB - PURPOSE: To analyze bronchial carcinoid characteristics that might influence
patterns of disease recurrence and overall survival in patients with these
tumors. MATERIALS AND METHODS: In a retrospective review, the actuarial rates of
local relapse, regional relapse, and overall survival were determined in patients
who had undergone resection of bronchial carcinoid tumors. The evaluable files
for 87 patients (50 male, 37 female; age range, 15-82 years) who underwent
resection of bronchial carcinoid cancer at the authors' institution between 1980
and 1993 were reviewed for pathologic findings, extent of disease, and recurrence
patterns after surgery. RESULTS: The actuarial 4-year overall survival, local
control, and regional control rates in the entire cohort of patients were 89%,
92%, and 94%, respectively. Univariate analyses revealed that an atypical
histologic pattern was the only tumor-related factor that substantially affected
local and regional control. Atypical histologic pattern and tumor size were among
the multiple factors that independently affected overall survival. CONCLUSION:
Atypical histologic findings in patients who had undergone complete resection of
bronchial carcinoid tumors were associated with increased local-regional disease
recurrence and decreased survival compared with recurrence and survival in
patients with typical histologic findings.
PMID- 9646812
TI - Hypertrophied bronchial artery at thin-section CT in patients with
bronchiectasis: correlation with CT angiographic findings.
AB - PURPOSE: To evaluate hypertrophied bronchial arteries on thin-section computed
tomographic (CT) scans in patients with bronchiectasis by using CT angiographic
correlation. MATERIALS AND METHODS: Spiral CT angiography was performed
prospectively in 14 patients (eight men, six women; age range, 34-71 years) with
bronchiectasis who were suspected of having bronchial arterial hypertrophy at
thin-section CT (performed without contrast medium). The inclusion criteria were
tubular (in six patients) or nodular (in 14 patients) areas of soft-tissue
attenuation that had an appearance unlike that of lymph nodes at thin-section CT
and that were within the mediastinum and around the central airway. These
findings were subsequently correlated with the spiral CT angiographic findings.
RESULTS: At comparative analysis of thin-section CT scans and CT angiograms,
seven of the eight (88%) tubular lesions and 19 of the 36 (53%) nodular lesions
in the mediastinal soft tissue were proved to be hypertrophied bronchial
arteries. All of the six (100%) tubular and 19 of the 21 (90%) nodular lesions
around the walls of the main (primary) and lobar bronchi were hypertrophied
bronchial arteries. In eight (57%) patients, CT angiograms showed 11 intraluminal
protrusions caused by hypertrophied bronchial arteries in the main bronchi, lobar
bronchi, or both. CONCLUSION: Nodular and tubular structures in the mediastinum
and around the central airway on thin-section CT scans in the patients with
bronchiectasis are suggestive of hypertrophied bronchial arteries. Recognition of
the hypertrophied bronchial artery can be critical for the bronchoscopist.
PMID- 9646813
TI - Ventilator-associated pneumonia in patients with adult respiratory distress
syndrome: CT evaluation.
AB - PURPOSE: To determine the diagnostic accuracy of computed tomography (CT) for
pneumonia in patients with adult respiratory distress syndrome (ARDS). MATERIALS
AND METHODS: CT scans were obtained within 1 week of bronchoscopic sampling in 31
patients receiving mechanical ventilation for ARDS for more than 48 hours. Of 11
patients with pneumonia, five developed symptoms less than 11 days after the
onset of ARDS (early ARDS). CT scans were rated for pneumonia independently by
four radiologists who were unaware of the clinical diagnosis. Diagnostic accuracy
was defined by means of the area under the receiver operating characteristic
curve, or A2. RESULTS: Diagnostic accuracy for pneumonia was fair (A2 = 0.69 +/-
0.04 [standard error]) owing to 70% true-negative ratings (vs 59% true-positive
ratings). The generalizability coefficient was good (0.79). No single CT finding
was significantly different for the presence of pneumonia. Nondependent opacities
predominated in 10 (91%) of 11 patients with pneumonia and 12 (60%) of 20 without
pneumonia. Nondependent opacities predominated in nine (56%) of 16 patients with
early ARDS and 13 (87%) of 15 with late ARDS. CONCLUSION: CT has fair diagnostic
accuracy for ventilator-associated pneumonia in patients with ARDS owing
primarily to identification of patients without pneumonia. No single CT sign was
significantly different for pneumonia, but dependent atelectasis was more common
in patients with early ARDS without pneumonia.
PMID- 9646814
TI - Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning-
correlation with pulmonary angiographic results or clinical outcome.
AB - PURPOSE: To compare the accuracy of spiral computed tomography (CT) with that of
ventilation-perfusion (V-P) scintigraphy in the diagnosis of pulmonary embolism
(PE). MATERIALS AND METHODS: Fifty-four patients in whom indeterminate V-P scans
or discordant clinical and scintigraphic results were obtained underwent both V-P
scanning and contrast material-enhanced spiral CT. The reference standard was
pulmonary angiographic results in 26 patients (group I) or clinical outcome in 28
(group II). RESULTS: Six (25%) of 24 group I patients had proved PE. The
prospective sensitivity and specificity for segmental or subsegmental PE were 67%
and 100%, respectively, and the positive and negative predictive values were 100%
and 90%, respectively. In two group II patients, V-P scans had high probability
for acute embolism, but spiral CT scans showed only chronic PE; in one patients,
the V-P scan had low probability and the CT scan was positive for acute PE. An
alternative CT diagnosis was established in four (31%) of 13 patients in whom a
normal or low-probability V-P scan was obtained. Clinical outcome was consistent
with spiral CT results in all cases. CONCLUSION: Spiral CT has greater accuracy
and specificity than V-P scanning in patients with an unresolved diagnosis and
may be useful as the primary screening technique for PE.
PMID- 9646815
TI - Unsuspected pulmonary embolism: prospective detection on routine helical CT
scans.
AB - PURPOSE: To determine the prevalence of unsuspected pulmonary embolism (PE) on
routine thoracic helical computed tomographic (CT) scans and to quantify the
improvement in PE detection by using a cine-paging mode on a workstation instead
of hard-copy review. MATERIALS AND METHODS: Seven hundred eighty-five patients
referred for routine contrast medium-enhanced thoracic CT within 9 months were
prospectively recruited. Helical CT was performed. Studies were prospectively
interpreted by four radiologists. Two radiologists performed routine, undirected,
hard-copy consensus review for official interpretation; two of three thoracic
radiologists independently performed a dedicated workstation-based search for PE.
The presence of PE involving the main, lobar, or segmental pulmonary arteries was
assigned a score of 1-5 (1 = definitely negative, 5 = definitely positive) by
each independent reviewer. Patients with a score of 4 or 5 underwent lower
extremity ultrasound, ventilation-perfusion scintigraphy, or both, followed by
pulmonary CT angiography if the findings were still equivocal. RESULTS: Twelve
(1.5%) of the 785 patients had unsuspected PE, with an inpatient prevalence of 5%
(eight of 160) and an outpatient prevalence of 0.6% (four of 625). Of the 12
patients with unsuspected PE, 10 (83%) had cancer. Of the 81 inpatients with
cancer, seven (9%) had unsuspected PE. A dedicated workstation-based search
resulted in detection of PE in three more patients (25%) than did hard-copy
interpretation. CONCLUSION: The prevalence of unsuspected PE was highest among
inpatients with cancer. A directed, workstation-based search can improve the PE
detection rate over that with hard-copy review.
PMID- 9646816
TI - Initially unresectable hilar cholangiocarcinoma: hepatic regeneration after
transarterial embolization.
AB - PURPOSE: To assess with volumetric computed tomography (CT) the pattern and
extent of hepatic regeneration induced with transarterial embolization of
initially unresectable hilar cholangiocarcinoma (Klatskin tumor). MATERIALS AND
METHODS: In this prospective study, 13 patients (four men, nine women) with hilar
cholangiocarcinoma, aged 43-74 years (mean +/- 1 standard deviation, 59.9 years
+/- 9.6), underwent preoperative embolization of the right hepatic lobe.
Embolization was performed transarterially by using four to 15 embolization
coils. Volumetric measurements of the entire liver, left hepatic lobe, and spleen
were performed with contrast material-enhanced and unenhanced helical CT before
and after embolization in all patients. RESULTS: After right lobe embolization,
volumetric helical CT measurements revealed a 2%-33% decrease (mean, 10%) in the
volume of the affected right hepatic lobe, an 11%-68% increase (mean, 37%) in the
volume of left hepatic lobe parenchyma, and variations in splenic volume of -5%
to +28% (mean, +11%). Nine patients underwent extended hepatectomy 27-75 days
(mean, 44 days) after embolization. No patient had severe complications due to
embolization. CONCLUSION: In patients with an initially unresectable bilateral
Klatskin tumor, right lobar arterial coil embolization results in enlargement of
the left hepatic lobe (as verified with volumetric helical CT), thus allowing
right hemihepatectomy.
PMID- 9646817
TI - Hepatic infarction secondary to arterial insufficiency in native livers: CT
findings in 10 patients.
AB - PURPOSE: To describe the computed tomographic (CT) appearance of hepatic infarcts
resulting from arterial insufficiency in native livers. MATERIALS AND METHODS:
The authors retrospectively reviewed the clinical and imaging findings in 10
patients (five men, five women; age range, 28-70 years) with 14 hepatic infarcts
seen over 3 years. CT scans were analyzed for infarct appearance, vessel patency,
and evolution of infarct pattern over time. RESULTS: Hepatic infarction resulted
from hepatobiliary surgery (n = 6), radiologic intervention (n = 3), and celiac
occlusion secondary to antiphospholipid syndrome (n = 1). All 14 infarcts were of
low attenuation, peripheral, and wedge-shaped. Occluded arterial vessels were
identified in eight patients. Follow-up CT revealed infarct diminution with
parenchymal atrophy and scarring (n = 5), progressive liquefaction (n = 2), or
both parenchymal atrophy and progressive liquefaction (n = 1). CONCLUSION: Sudden
interruption of hepatic arterial flow may cause acute native liver infarction.
Patients at risk include those with underlying vascular disease who undergo
complicated surgical procedures and those undergoing peripheral arterial
embolization.
PMID- 9646818
TI - Mucin-producing pancreatic tumors: comparison of MR cholangiopancreatography with
endoscopic retrograde cholangiopancreatography.
AB - PURPOSE: To compare magnetic resonance cholangiopancreatography (MRCP) with
endoscopic retrograde cholangiopancreatography (ERCP) in the detection of mucin
producing pancreatic tumors. MATERIALS AND METHODS: The authors retrospectively
reviewed MRCP and ERCP images obtained in 28 patients with mucin-producing
pancreatic tumors. Detectability of the pancreatic duct and its branches,
intraductal cystic lesions, and intracystic nodules or septa was assessed.
RESULTS: MRCP depicted cystic dilated ductal branches significantly better than
did ERCP (P < .001). The difference in the number of nodules or septa detected
with MRCP compared with ERCP was not significant. MRCP, however, simultaneously
showed not only the main pancreatic duct but also the cystic lesions; this was
not always possible with ERCP. CONCLUSION: MRCP appears to be more effective and
less invasive than ERCP to evaluate changes in the size and extent of tumors and
to determine if new lesions appear, as well as to follow up mucin-producing
pancreatic tumors.
PMID- 9646819
TI - Gastric mucosa-associated lymphoid tissue lymphoma: radiographic findings in six
patients.
AB - PURPOSE: To determine the radiographic findings of low-grade gastric mucosa
associated lymphoid tissue (MALT) lymphoma on double-contrast upper
gastrointestinal studies. MATERIALS AND METHODS: Pathology records, double
contrast upper gastrointestinal studies, and medical records of six patients with
gastric MALT lymphoma were retrospectively reviewed. RESULTS: The most common
clinical findings at presentation included epigastric pain (n = 6), dyspepsia (n
= 4), and nausea and vomiting (n = 4). Double-contrast studies revealed rounded,
often confluent nodules of varying size in four patients with low-grade MALT
lymphoma. Nodularity was located in the gastric antrum (n = 2), body (n = 1), or
body and fundus (n = 1). A fifth patient had a malignant-appearing 1-cm-diameter
antral ulcer, and a sixth had a 10-cm-diameter polypoid, ulcerated mass in the
gastric fundus. The latter patient was found to have high-grade MALT lymphoma
with low-grade MALT lymphoma abutting the tumor. Five patients had associated
Helicobacter pylori gastritis. Five patients had stage I disease, and one had
stage IIB disease. At endoscopic follow-up (n = 4), marked regression of tumor
occurred after treatment with antibiotics, chemotherapy, and/or radiation
therapy. CONCLUSION: When low-grade MALT lymphoma is suspected on the basis of
barium study results, endoscopic biopsy specimens should be obtained for a
definitive diagnosis so these patients can be treated before the development of
high-grade gastric lymphoma.
PMID- 9646820
TI - Screening behavior of women after a false-positive mammogram.
AB - PURPOSE: To determine the effect of a false-positive mammogram that leads to open
surgical biopsy on subsequent screening mammography behavior in women. MATERIALS
AND METHODS: This study was performed with a retrospective cohort design, and
data were collected by means of telephone interview. All participants were women
aged at least 50 years, with no history of breast cancer. Study patients (n = 43)
were women who had an abnormal mammogram followed within 6 months by benign
excisional breast biopsy. Control subjects (n = 136) were randomly selected: They
included women with a normal mammogram who had not undergone biopsy, as well as
women with an abnormal mammogram and the recommendation to undergo 6-month follow
up mammography. RESULTS: Two differences between the study and control groups
were statistically significant. Study patients were more likely than control
patients to believe they had increased susceptibility to breast cancer (P =
.039). Study patients were also more likely than control subjects to intend to
undergo screening mammography annually in the future (P = .036). CONCLUSION: A
false-positive mammogram that leads to open surgical biopsy does not inhibit most
women from undergoing subsequent screening mammography. In fact, such an
experience may increase their intentions to undergo regular screening.
PMID- 9646821
TI - Calcification retrieval at stereotactic, 11-gauge, directional, vacuum-assisted
breast biopsy.
AB - PURPOSE: To determine the frequencies of calcification retrieval and histologic
underestimates at stereotactic, 11-gauge, directional, vacuum-assisted breast
biopsy. MATERIALS AND METHODS: Retrospective review of records revealed 112
calcific lesions in 80 women (aged 31-85 years) who underwent stereotactic, 11
gauge, directional, vacuum-assisted biopsy; a mean of 14 specimens per lesion
were obtained. Calcification retrieval was defined as identification of
calcifications on radiographs of specimens. Atypical ductal hyperplasia (ADH)
underestimates were lesions that yielded ADH at stereotactic biopsy and carcinoma
at surgery. Ductal carcinoma in situ (DCIS) underestimates were lesions that
yielded DCIS at stereotactic biopsy and infiltrating carcinoma at surgery.
Mammograms, stereotactic images, radiographs of specimens, and histologic
findings were reviewed. RESULTS: Stereotactic, 11-gauge, directional, vacuum
assisted biopsy removed all calcifications in 51 (46%) lesions, some
calcifications in 55 (49%) lesions, and no calcifications in six (5%) lesions.
Failure to retrieve calcifications was significantly more likely in lesions 5 mm
or smaller (12% [five of 43] vs 1% [one of 69], P = .03), in calcifications with
amorphous morphology (21% [three of 14] vs 3% [three of 98], P < .03), or if the
probe was fired outside the breast (12% [five of 40] vs 1% [one of 72], P = .02).
Surgery revealed DCIS in one (10%) of 10 lesions that yielded ADH at stereotactic
biopsy. Surgery revealed infiltrating carcinoma in one (5%) of 21 lesions that
yielded DCIS at stereotactic biopsy. No underestimation occurred when all
calcifications were removed. CONCLUSION: Stereotactic, 11-gauge, directional,
vacuum-assisted biopsy resulted in successful calcification retrieval in 106
(95%) of 112 cases. Histologic underestimation was infrequent.
PMID- 9646822
TI - Vogele-Bale-Hohner mouthpiece: registration device for frameless stereotactic
surgery.
PMID- 9646823
TI - Pneumothorax after fine-needle aspiration biopsy.
PMID- 9646824
TI - Liver hemangioma: US-guided core-needle biopsy.
PMID- 9646825
TI - Specimen weights obtained with 14- and 11-gauge breast biopsy probes.
PMID- 9646826
TI - Hard- versus soft-copy readings of computed radiographs.
PMID- 9646827
TI - Human chorionic gonadotropin levels in the evaluation of ectopic pregnancy.
PMID- 9646828
TI - Silicone gel and animal models of autoimmune disease.
PMID- 9646829
TI - Apoptosis and thyroiditis.
AB - The origin of the various forms of autoimmune thyroiditis remains unclear. Most
investigations into the pathogenesis of these disorders have focused on immune
abnormalities that might lead to an autoimmune response. However, no unique
immune response to thyroid autoantigens has been identified that either is
limited to patients with thyroiditis or is absolutely correlated with clinical
disease expression. CD8 T-cell-mediated cytotoxicity is thought to be a major
cause of thyroid follicular cell damage in thyroiditis. This damage is produced
in part through the induction of apoptosis in thyroid cells. Recent studies have
demonstrated that programmed cell death is regulated in thyroid cells and that a
major pathway for immune-mediated apoptosis, the Fas pathway, is blocked by
labile inhibitors in a manner that could prevent cytotoxicity. This review also
examines several other types of regulation of apoptotic pathways in thyrocytes.
We hypothesize that the regulation of programmed cell death pathways in the
thyroid may alter the expression of autoimmune thyroid diseases by modifying the
susceptibility of thyroid cells to immune-mediated apoptosis.
PMID- 9646830
TI - Lymphotactin.
PMID- 9646831
TI - Smokeless tobacco extracts activate complement in vitro: a potential pathogenic
mechanism for initiating inflammation of the oral mucosa.
AB - The use of smokeless tobacco has been linked to an increased incidence of
inflammation of the buccal and gingival mucosa. However, the mechanisms by which
smokeless tobacco initiates inflammation are not well understood. The complement
cascade is a ubiquitous source of proinflammatory molecules and can be activated
rapidly by a wide variety of agents. Therefore, the effect of smokeless tobacco
on complement was investigated as a potential pathogenic mechanism for triggering
inflammation of the oral mucosa. Aqueous extracts of loose leaf chewing tobacco
(1S1), dry snuff (1S2), and moist snuff (1S3), added to normal human serum,
depleted complement hemolytic activity in a dose-dependent manner. Experiments
utilizing sera deficient in one specific complement component indicated that the
smokeless tobacco-induced depletion of hemolytic activity was due largely to
consumption of C3. Furthermore, assays designed to test the activity of the
alternative pathway of complement clearly showed that all three extracts depleted
the hemolytic activity of this pathway. Finally, all three smokeless tobacco
extracts activated the alternative pathway since significantly elevated levels of
the cleavage fragments iC3b and Bb were detected in extract-treated serum. High
quantities of the classical pathway cleavage fragment C4d also were detected in
serum treated with moist snuff (1S3). The results clearly demonstrate that
smokeless tobacco extracts activate the alternative pathway and also suggest some
measure of classical pathway activation. Activation of complement by smokeless
tobacco may be a mechanism for initiating inflammation of the oral mucosa.
PMID- 9646832
TI - Differential expression of bcl-2 and susceptibility to programmed cell death in
lymphocytes of HIV-1-infected individuals.
AB - The bcl-2 protooncogene encodes an inner mitochondrial membrane protein that
blocks programmed cell death. There is now increasing evidence that regulation of
bcl-2 expression is a determinant of life or death in normal lymphocytes. In this
study, we examined bcl-2 expression in lymphocytes from human immunodeficiency
virus type 1 (HIV-1)-infected and healthy subjects by flow cytometry. bcl-2
expression was detected in more than 97% of peripheral blood lymphocytes in both
healthy and HIV-infected individuals. It was consistently observed that CD4+
lymphocytes from HIV-1-infected individuals with less than 200 CD4+
cells/microliter expressed significantly less bcl-2 than healthy controls. In
contrast, bcl-2 expression in CD8+ lymphocytes of these patients was
significantly enhanced. No significant alteration of bcl-2 expression was found
when lymphocytes of healthy individuals were polyclonally activated in the
presence of various regulatory cytokines. Cells undergoing apoptosis showed
significantly lower bcl-2 expression than viable cells. Staining of apoptotic
cells revealed that lymphocytes from HIV-1-infected subjects were characterized
by an increased susceptibility to programmed cell death which was not restricted
to a particular lymphocyte subset. Despite significantly different bcl-2
expression in CD4+ and CD8+ lymphocytes of HIV-1-infected individuals with less
than 200 CD4+ cells/microliter, no difference could be observed concerning their
susceptibility to undergo apoptosis. Therefore, we conclude that sensitivity or
resistance to in vitro induction of apoptosis does not directly correlate with
bcl-2 expression.
PMID- 9646833
TI - Cell death and oxidative damage in inflammatory myopathies.
AB - There is evidence that muscle fibers in denervating disorders and muscular
dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory
myopathies, we found no features of muscle fiber apoptosis such as DNA
fragmentation or expression of apoptosis-related proteins. However, muscle fibers
in myositis displayed distinct up-regulation of inducible and neuronal nitric
oxide synthase (NOS). While inducible NOS was distinctly up-regulated on the
sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased
expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There
were no disease-specific patterns in the different myositis subtypes. Enhanced
expression of NOS with production of nitric oxide may contribute to oxidative
stress mediating muscle fiber damage and muscle fiber necrosis representing the
predominant cell death mechanism in myositis. Nevertheless, inflammatory cells
displayed numerous DNA-fragmentation-positive nuclei and expression of apoptosis
related proteins indicating that apoptosis plays a role in the regulation of the
inflammatory cellular response.
PMID- 9646834
TI - Silicone gel enhances the development of autoimmune disease in New Zealand black
mice but fails to induce it in BALB/cAnPt mice.
AB - Anecdotal evidence links silicone gel breast implants with the development of
autoimmune connective tissue disease in women. To investigate whether silicone
gel is capable of directly inducing and/or enhancing the development of
autoimmune disease, female BALB/cAnPt (BALB/c) and New Zealand Black (NZB) mice
were injected subcutaneously with silicone gel, pristane, a nonmetabolizable
substance that can cause plasmacytomas in BALB/c and NZB mice, or saline and
monitored for the development of glomerulonephritis and autoantibody production.
NZB, but not BALB/c, mice spontaneously develop autoantibodies and an autoimmune
hemolytic anemia by 12 months of age. Over a period of 10 months, biweekly
screening for proteinuria revealed increases in urinary protein in NZB mice that
received multiple injections of either silicone gel or pristane. In contrast,
urinary protein was unaffected in identically treated BALB/c mice. Although,
silicone gel had no effect on serum titers of antierythrocyte antibodies in NZB
mice, the hematocrits were significantly decreased. Moreover, silicone gel both
increased the concentration of IgM anti-type I collagen antibodies and skewed the
immunofluorescent staining pattern of serum autoantibodies on HEp-2 cells. In
contrast, silicone gel failed to induce the production of anti-erythrocyte or
antinuclear antibodies in BALB/c mice and induced only slight increases in IgG
anti-type I collagen antibodies. These results suggest that silicone gel can
exacerbate the development of autoimmune disease in autoimmune NZB mice, but
fails to induce disease in normal BALB/c mice. This is consistent with several
epidemiological studies failing to demonstrate an increase in the incidence of
autoimmune disease in women with breast implants. However, because silicone gel
was able to exacerbate autoimmune disease in NZB mice, it may play a similar role
in the development of autoimmune disease in a small percentage of women who are
genetically susceptible to such diseases.
PMID- 9646835
TI - Effect of aging on experimental autoimmune prostatitis: differential kinetics of
development.
AB - We have studied the influence of aging on the kinetics of autoimmune response in
Experimental Autoimmune Prostatis (EAP). EAP was induced in 3- and 12-month-old
Wistar rats by i.d. immunization with a saline extract of rat male sex accessory
glands (RAG), chemically modified, and emulsioned in CFA. After immunization, 12
month-old rats developed a faster and stronger specific DTH response against RAG
and mononuclear infiltration in the prostate. The levels of total IgM and IgG
against RAG were lower in 12-month-old rats than in 3-month-old rats, with a
prevalence of IgG2a, IgG2b, and IgG2c subclasses in both ages. Immunization
stimulated slightly the appearance of specific IgG1 to RAG only in 3-month-old
rats but in 12-month-old rats there was no specific IgG1 to RAG. On the other
hand, normal 12-month-old rats showed higher levels of some natural antibodies
and their thymocytes and peripheral lymphocytes had a diminished proliferative
capacity compared to 3-month-old rats. These data demonstrated that 12-month-old
rats show parameters of an aged immune system and present an exacerbated
autoimmune prostatitis compared with 3-month-old rats.
PMID- 9646836
TI - The effect of B cell deficiency on the immune response to acetylcholine receptor
and the development of experimental autoimmune myasthenia gravis.
AB - To study the involvement of B cells in the immune response to acetylcholine
receptor (AChR), B-cell-deficient (mu mutant) and control wild-type C57BL/6 mice
were immunized with AChR and assessed for clinical and immunopathological
manifestations of experimental autoimmune myasthenia gravis (EAMG). The mu mutant
mice failed to generate anti-AChR antibodies and were completely resistant to the
induction of EAMG. However, mu mutant mice developed clinical EAMG when
antibodies to the AChR main immunogenic region were passively transferred.
Further, the in vivo expansion of lymph node cells after AChR immunization was
greatly impaired in mu mutant mice. The mu mutant mice gave an effective in vitro
T cell immune response to the immunodominant pathogenic AChR alpha chain peptide
146-162 (alpha 146-162) and to the whole AChR protein when tested on day 90 after
immunization with AChR, whereas the response to both AChR and its alpha 146-162
peptide was reduced when tested on day 7 after immunization. The in vitro
production of IFN-gamma and IL-2 by AChR-specific and alpha 146-162 peptide
specific lymphocytes was lower in mu mutant mice. The AChR immune mu mutant T
cells proliferated and produced IFN-gamma when AChR or alpha 146-162 peptide was
presented by wild-type irradiated AChR-primed antigen-presenting cells (APCs).
This indicates that B cells are important in the processing and presentation of
AChR dominant peptide in vitro during the initial immune response to AChR.
However, APCs of non-B-cell lineage are sufficient to process AChR and prime the
T cells to AChR dominant T cell epitope peptides.
PMID- 9646837
TI - Eye muscle antibodies in patients with ocular myasthenia gravis: possible
mechanism for eye muscle inflammation in acetylcholine-receptor antibody-negative
patients.
AB - Myasthenia gravis is an organ-specific autoimmune disorder generally thought to
be caused by an antibody-mediated attack against the skeletal muscle nicotinic
acetylcholine (Ach) receptor (AchR) at the neuromuscular junction. Extraocular
muscle weakness and double vision are present in about 90% of patients with
myasthenia gravis and are the predominant complaints in about 20% of patients,
when the condition is called ocular myasthenia gravis (OMG). While serum
antibodies against the AchR are detected in most patients with generalized
myasthenia gravis (GMG), they are not found in about one-third of patients with
the ocular variety, and epidemiological, clinical, and serological studies
suggest that OMG and GMG are two separate diseases. Both forms of myasthenia
gravis are sometimes associated with thyroid autoimmunity or thyroid-associated
ophthalmopathy (TAO). We have therefore tested the sera of patients with GMG and
OMG by Western blotting for antibodies against porcine eye muscle membrane
proteins in general, and by enzyme-linked immunosorbent assays (ELISA)
specifically for reaction with two skeletal muscle antigens which are prominent
marker antigens for TAO, namely, the calcium-binding protein calsequestrin and
the so-called "64-kDa protein." The 64-kDa protein has recently been identified
as the flavoprotein subunit of mitochondrial succinate dehydrogenase. Patients
with ophthalmopathy and myasthenia were excluded. Nine of the patients had
associated Graves' hyperthyroidism without evident ophthalmopathy and one had
Hashimoto's thyroiditis. Antibodies against porcine eye muscle membrane antigens
of M(r) 15-110 kDa were detected in patients with GMG or OMG, one or more
antibodies being detected in 100% of patients with GMG and in 88% of those with
OMG. The most frequently found antibodies were those targeting eye muscle
membrane proteins of 15, 67, and 110 kDa. Antibodies reactive with purified
calsequestrin (63 kDa) were detected in 21% of patients with OMG but in no
patient with GMG. Antibodies recognizing purified succinate dehydrogenase (67
kDa) were found in 42% of patients with OMG, in 100% (5 of 5) of patients with
GMG, and in 48% of all patients with myasthenia gravis not associated with
Graves' hyperthyroidism. There was no close correlation between any eye muscle
reactive antibody and antibodies against the AchR in either group of myasthenic
patients. The findings support the notion that immunoreactivity against skeletal
muscle proteins other than the AchR may play a role in the development of the
muscle weakness in AchR antibody-negative patients with OMG and GMG, although it
is unlikely that any of the antibodies demonstrated in this study are directly
implicated. Similarly, while the demonstration of antibodies reactive with eye
muscle antigens associated with TAO in patients with OMG raises the possibility
that the link between the ocular lesions of myasthenia gravis and Graves' disease
may be autoimmunity against a common antigen(s), it is more likely that both
disorders are mediated by cytotoxic T cells recognizing another cell membrane
antigen, such as the novel thyroid and eye muscle shared protein G2s, and that
serum antibodies reactive with succinate dehydrogenase Fp subunit and
calsequestrin are markers of an immune-mediated eye muscle reaction.
PMID- 9646838
TI - Induction of oral tolerance in splenocyte-reconstituted SCID mice.
AB - The participation of each lymphocyte compartment in the induction of oral
tolerance for antibody response was investigated by means of a new cell-transfer
experimental system, using severe combined immunodeficiency (SCID) mice. Various
lymphocyte compartments from BALB/c mice were transferred into SCID mice and
these mice were evaluated for oral tolerance induction. First, whole splenocytes
from BALB/c mice were transferred into SCID mice and these mice were orally
administered bovine alpha s1-casein. The specific antibody response in these mice
after subsequent immunization with antigen was greatly reduced compared to
controls which were not fed the antigen, and it was demonstrated that oral
tolerance was induced in SCID mice bearing donor splenocytes. Oral tolerance was
induced in SCID mice that were reconstituted with only T cells, revealing that B
cells were not required for the induction of oral tolerance. Further, oral
tolerance was induced in SCID mice reconstituted with CD8-depleted splenocytes
but not in mice reconstituted with only CD8+ T cells. These results demonstrate
that oral tolerance could be induced in SCID mice bearing normal splenocytes and
that interaction of CD4+ T cells with antigen-presenting cells other than B cells
are responsible for the induction of oral tolerance. Our experimental system may
be useful for investigations with human lymphocytes.
PMID- 9646839
TI - The association between anti-ribosomal P antibodies and active nephritis in
systemic lupus erythematosus.
AB - Autoantibodies to anti-ribosomal P protein have been recognized in patients with
systemic lupus erythematosus (SLE) in widely variable proportions of unselected
patients. Presence of anti-ribosomal P antibodies was retrospectively studied in
69 patients with SLE during disease exacerbations and remissions or during
continuously active disease. Anti-ribosomal P antibodies were positive in 21/69
patients during active disease, with an overall prevalence of 30.4%. Prevalence
in patients with active nephritis was 75.0% (15/20), P value by Fisher's exact
test of 8.39 x 10(-7). In 12/13 patients (92.3%), anti-P disappeared during
periods of disease remission, P = 0.0002. In 17/21 patients (81.0%) with anti
ribosomal P antibodies, anti-dsDNA antibodies were also positive. In 47 patients
without anti-P, 23/47 (48.9%) were also positive for anti-dsDNA. In 9/12 patients
(75.0%) titers of anti-dsDNA antibodies correlated with anti-P during disease
exacerbations and remissions, P = 0.004. The higher prevalence of anti-P in
patients with lupus nephritis with disappearance during disease remissions
supports the hypothesis of an immunopathogenetic role of these antibodies in
lupus nephritis. There was also a strong association between anti-dsDNA and anti
P antibodies.
PMID- 9646840
TI - Complement system is not activated in primary biliary cirrhosis.
AB - There is controversial evidence suggesting that the classical pathway of
complement system is chronically activated in primary biliary cirrhosis (PBC) and
that complement activation may be important in development of bile duct injury.
We have reevaluated this issue by measuring by-products of complement activation
such as C4a, C3a, Bb, and terminal complement complexes (SC5b-9) in plasma of 44
PBC patients with sensitive methods not previously used to detect complement
activation in this disease. Age-matched healthy women and patients with chronic
hepatitis of different etiology were studied as controls. We found that PBC
patients have normal C4a concentrations. This finding argues strongly against
chronic classical pathway activation. Although a minor increase of C3a levels was
observed in a minority of PBC patients, the C3a/C3 ratio, an index used to
evaluate the extent of native protein conversion, was remarkably similar in all
groups. Potentially lytic terminal complement complexes were not increased. PBC
patients had normal Bb plasma levels, indicating that the alternative pathway is
also not activated. C3 concentration was higher in PBC patients than in healthy
subjects and in chronic hepatitis patients, particularly in the early stages of
the disease. C3 and C4 concentrations became lower in PBC and chronic hepatitis
with the progression of the disease. The increase of C3 concentration in PBC does
not reflect liver inflammation, since serum levels of C-reactive protein are
normal. We found high serum C3 levels in patients with rare chronic cholestatic
syndromes without superimposed infections and observed that serum C3 levels
paralleled those of bilirubin in a patient with benign recurrent intrahepatic
cholestasis. In conclusion, our data indicate that complement is not activated in
PBC and that the increase of serum C3 levels is related to cholestasis.
PMID- 9646841
TI - Human neutrophils express the prostaglandin G/H synthase 2 gene when stimulated
with bacterial lipopolysaccharide.
AB - Human blood neutrophils (PMN) rapidly release arachidonic acid (AA) from cellular
phospholipids when stimulated in vitro with a variety of inflammatory agonists.
Free AA is then metabolized via 5'-lipoxygenase to produce bioactive mediators
such as leukotriene B4 and 5-hydroxyeicosatetraenoate. Arachidonic acid can also
be metabolized via the cyclooxygenase or prostaglandin G/H synthase (PGHS)
pathway to form prostaglandins and thromboxane. We show here that human blood PMN
express the PGHS 2 gene when stimulated with bacterial lipopolysaccharide (LPS).
PGHS 2 mRNA increases within 30 min after LPS stimulation and PGHS 2
immunoreactive protein is detectable by 5 h. Although PGHS 1 mRNA is detectable
in PMN, no immunoreactive protein is observed in either resting or LPS-stimulated
cells. Following stimulation with LPS and expression of PGHS 2, PMN increase
secretion of prostaglandin E2. This phenotypic change in PMN could be an
important mechanism for regulating inflammation.
PMID- 9646842
TI - IL-1 receptor antagonist (IL-1RA) gene polymorphism in Sjogren's syndrome and
rheumatoid arthritis.
AB - The gene encoding interleukin-1 receptor antagonist (IL-1ra) has a variable
allelic polymorphism. The IL1RN*2 allele was recently described as a factor of
severity in several autoimmune diseases and was paradoxically associated with
increased production of IL-1ra by monocytes in vitro. We studied this
polymorphism in 36 patients with possible or definite primary Sjogren's syndrome
and found that IL1RN*2 was significantly more frequent in the definite than in
the possible form. In rheumatoid arthritis, the frequency of the allele was not
different from that of controls. The serum levels of IL-1ra were markedly higher
in Sjogren patients than in those of healthy subjects. By contrast, the salivary
IL-1ra levels were decreased. Patients with the allele generally had lower
salivary levels and higher serum levels than patients without the allele. In the
group of patients with the definite syndrome, CRP and TGF-beta 1, two in vitro
stimulators of IL-1ra production, were correlated with IL-1ra serum levels. Our
results suggest that IL1RN*2 is a marker of more severe forms of Sjogren's
syndrome. Its effect on salivary and serum IL-1ra may be distinct, suggesting
separate regulatory mechanisms.
PMID- 9646843
TI - Molecular and cellular events in early thymocyte development.
PMID- 9646844
TI - Regulation of immunoglobulin light chain isotype expression.
PMID- 9646845
TI - Role of immunoreceptor tyrosine-based activation motif in signal transduction
from antigen and Fc receptors.
PMID- 9646846
TI - The atypical serine proteases of the complement system.
PMID- 9646847
TI - Accessibility control of V(D)J recombination: lessons from gene targeting.
PMID- 9646848
TI - Interactions between the immune system and gene therapy vectors: bidirectional
regulation of response and expression.
PMID- 9646849
TI - How do major histocompatibility complex genes influence odor and mating
preferences?
PMID- 9646850
TI - Olfactory receptor gene regulation.
PMID- 9646851
TI - [Undertreatment of patients with pain has to be stopped. New therapeutic
prospectives with retard tilin/naloxone].
PMID- 9646852
TI - Modifications to the in situ TUNEL method for detection of apoptosis in paraffin
embedded tissue sections.
AB - The in situ detection of cells undergoing apoptosis is increasingly important in
the analysis of injury and degeneration in the central nervous system. Limited
information is presently available on the quantification of apoptosis in paraffin
embedded brain tissue sections, a technique which would be most useful in the
evaluation of archival tissue for diagnostic and experimental purposes. In this
report, optimized conditions for tissue digestion and permeabilization using
Proteinase K and Triton X and a quantification method for apoptosis detection are
described using brain sections from aluminum maltolate-treated aged and young
rabbits as compared to untreated matched controls. This method provides optimal
staining of apoptotic cells without the problem of tissue destruction, and should
prove useful in evaluating the process of apoptosis in neurodegenerative
disorders.
PMID- 9646853
TI - Expression of HER-2/neu oncogene in normal, hyperplastic, and malignant
endometrium.
AB - HER-2/neu oncogene is believed to be involved in tumorigenesis of several human
malignancies. To assess the pattern of expression of this oncogene in normal,
hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to
paraffin-embedded tissue sections obtained from 146 patients with endometrial
adenocarcinoma. A spectrum of hyperplastic changes ranging from simple
hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases.
Expression for HER-2/neu oncogene was demonstrated as cell membrane staining.
Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous
expression for HER-2/neu oncogene. The intensity of the immunostaining and the
number of cells stained for HER-2/neu oncogene had no significant association
with surgical stage or histologic grade, although the proportion of patients
demonstrating overexpression increased significantly as the histologic grade of
their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a
statistically significant correlation was found between the level of expression
of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated
that HER-2/neu oncogene expression is variably present in normal and hyperplastic
endometrium. Association between HER-2/neu oncogene expression, higher grade
lesions and poor survival in patients with endometrial cancer may also justify
assessment of HER-2/neu oncogene as a reliable prognostic indicator.
PMID- 9646854
TI - Postmortem diagnosis of hemoglobin SC disease complicated by fat embolism.
AB - A case is reported of a previously healthy 52-year-old African American male who
presented with acute onset of abdominal pain. Progressive increase in his
abdominal symptoms led to an exploratory laparotomy; however, no pathology was
discovered. Postoperatively, the patient became hypoxemic which progressed to
diffuse infiltrates on chest x-ray, suggestive of adult respiratory distress
syndrome. He had a rapidly fatal course. Autopsy showed bone marrow infarction,
fat embolism, splenomegaly, and widespread congestion with sickle erythrocytes.
Hemoglobin electrophoresis done postmortem showed hemoglobin (Hb) SC disease that
was undiagnosed antemortem. To the best of our knowledge, it is unusual for Hb SC
to be diagnosed postmortem in adults. This case suggests that sickle cell
disorders should be ruled out in patients at risk for hemoglobinopathy in the
presence of signs and symptoms compatible with the disease, irrespective of age.
PMID- 9646855
TI - HLA-Dr negative acute non-lymphocytic leukemia.
AB - Absent or diminished HLA-Dr antigen representation on the cell surface of both
normal and leukemic promyelocytes is a hallmark of this stage of myeloid
maturation. In order to document the specificity of this finding for acute
promyelocytic leukemia, flow cytometric analysis of leukemic blasts was utilized
on 36 cases of acute non-lymphocytic leukemia. All 15 of the promyelocytic
leukemias (FAB-M3) studied showed absent or markedly decreased HLA-Dr antigen on
their cell surface. However, the majority of cases (21) in which this finding was
noted were other than promyelocytic leukemias and included all FAB subtypes, most
particularly FAB-M2, i.e., myeloblastic leukemia with maturation. It is concluded
that absent to decreased HLA-Dr antigen representation on leukemic blasts lacks
specificity and can be seen in all acute myeloid/monocytic leukemic subtypes.
PMID- 9646856
TI - Phospholipid-independent binding of beta 2glycoprotein I by IgA from patients
with antiphospholipid syndrome.
AB - beta 2glycoprotein I (beta 2GPI) is a phospholipid-binding protein of the
coagulation system. In patients with the antiphospholipid syndrome (APS),
antibodies to beta 2GPI contribute to the population of "antiphospholipid
antibodies" measured in the anticardiolipin antibody (aCL) assay. In fact, both
IgG and IgM antibodies from patients with APS bind beta 2GPI in the absence of
anionic phospholipids if the antigen is bound to a suitable surface, i.e., one
which exposes the epitope. The binding of IgA was studied from patients with APS,
using an enzyme-linked immunosorbent assay (ELISA), and significantly higher
binding of IgA was observed from 39 patients compared to a control group of 50
healthy individuals (p < 0.0001). Moreover, 15 out of 39 APS subjects (38
percent) exhibited binding greater than 5 standard deviations (SD) above the mean
of the control group. All 39 APS patients had elevated IgG anti-beta 2GPI;
however, depletion of IgG from two APS sera diminished, rather than enhanced,
binding of IgA. Pre-incubation with purified IgG from a subject with APS led to
inhibition of IgA binding at inhibitor levels > 125 micrograms IgG/well. These
data demonstrate that patients with APS have IgA anti-beta 2GPI autoantibodies
and that the epitope(s) which are recognized by these antibodies can be presented
in the absence of cardiolipin or other anionic phospholipids.
PMID- 9646857
TI - Stability of cannabinoids in urine in three storage temperatures.
AB - Stability of cannabinoid compounds in urine samples were evaluated using several
storage temperatures. Appreciable losses (> 22.4 percent) were observed in some
urine samples, after being stored at room temperature for 10 days. Lower losses
(8.1 percent) were observed when the urine samples were refrigerated for 4 weeks.
The behavior of urine samples depended on the analyzed urine. This could be due
to the different stability of the cannabinoids present in each urine sample.
Important losses of 8.0 +/- 10.6, 15.8 +/- 4.2, and 19.6 +/- 6.7 percent were
found when the urine samples were frozen during 40 days, 1 year, and 3 years,
respectively. Average losses (> > 5 percent) can be observed after one day which
could mainly be due to the decrease of the solubility of 11-nor-U9
tetrahydrocannabinol-9-carboxylic acid (THC-COOH) or adsorption process of
cannabinoid molecules to the plastic storage containers.
PMID- 9646858
TI - Long-term maintenance of immunity in patients with common variable immune
deficiency by plasma transfusion.
AB - The AIDS crisis and the fear of blood product contamination stimulated the
development of a designated plasma collection and transfusion for patients with
common variable immune deficiency. Four patients have been maintained over 1
year; 5 years and 10 months; 8 years and 7 months; and 12 years. A new crisis
affecting commercial IgG manufacturing, owing to recalls, has made the life
saving product scarce, threatening patients' health maintenance. Our experience
over a long time has demonstrated that plasma transfusion is equivalent to
management with commercial IgG. The program of product collection and patient
management includes testing the collected plasma for IgG content, selecting ABO
compatible plasma, and following patients with IgG trough levels, prior to each
transfusion, to assure sufficient immune globulin administration.
PMID- 9646859
TI - The incidence of elevations in urine 5-hydroxyindoleacetic acid.
AB - A 24-hour urine collection for 5-hydroxyindoleacetic acid (HIAA) is commonly
performed to evaluate patients with suspected carcinoid syndrome. However,
carcinoids are rare, and elevated results are common even when using an
analytically specific method. To characterize this problem, the incidence of
elevated results was examined in a population of 947 patient specimens received
in a clinical reference laboratory setting. Using a reference limit of 15 mg/d
identified 7.9 percent of the results as elevated, with 3 percent > 100 mg/d, and
about 1 percent > 350 mg/d. Males showed 14 percent > 15 mg/d compared to 5.2
percent for females. Characterization of incomplete and excess 24-hr urine
collections is facilitated by use of a creatinine ratio, with a reference limit
of 14 mg/g creatinine equivalent to 15 mg/d. Given the frequency of elevated
results, HIAA should be used to support the diagnoses of carcinoid only when
consistent with other objective findings.
PMID- 9646860
TI - The stereochemical mechanism of the cooperative effects in hemoglobin revisited.
AB - In 1970, Perutz tried to put the allosteric mechanism of hemoglobin, proposed by
Monod, Wyman and Changeux in 1965, on a stereochemical basis. He interpreted
their two-state model in terms of an equilibrium between two alternative
structures, a tense one (T) with low oxygen affinity, constrained by salt-bridges
between the C-termini of the four subunits, and a relaxed one (R) lacking these
bridges. The equilibrium was thought to be governed primarily by the positions of
the iron atoms relative to the porphyrin: out-of-plane in five-coordinated, high
spin deoxyhemoglobin, and in-plane in six-coordinated, low-spin oxyhemoglobin.
The tension exercised by the salt-bridges in the T-structure was to be
transmitted to the heme-linked histidines and to restrain the movement of the
iron atoms into the porphyrin plane that is necessary for oxygen binding. At the
beta-hemes, the distal valine and histidine block the oxygen-combining site in
the T-structure; its tension was thought to strengthen that blockage. Finally,
Perutz attributed the linearity of proton release with early oxygen uptake to the
sequential rupture of salt-bridges in the T-structure and to the accompanying
drop in pKa of the weak bases that form part of them. Almost every feature of
this mechanism has been disputed, but evidence that has come to light more than
25 years later now shows it to have been substantially correct. That new evidence
is reviewed below.
PMID- 9646861
TI - The three-dimensional structure of the ribosome and its components.
AB - Exciting progress has been made in the last decade by those who use physical
methods to study the structure of the ribosome and its components. The structures
of 10 ribosomal proteins and three isolated ribosomal protein domains are known,
and the conformations of a significant number of rRNA sequences have been
determined. Electron microscopists have made major advances in the analysis of
images of ribosomes, and microscopically derived ribosome models at resolutions
approaching 10A are likely quite soon. Furthermore, ribosome crystallographers
are on the verge of phasing the diffraction patterns they have had for several
years, and near-atomic resolution models for entire ribosomal subunits could
emerge from this source at any time. The literature relevant to these
developments is reviewed below.
PMID- 9646862
TI - Signaling complexes: biophysical constraints on intracellular communication.
AB - This review surveys the kinds of protein complex that participate in cell
communication and identifies, where possible, general principles by which they
form and act. It also advances the notion that biophysical constraints imposed by
macromolecular crowding and diffusion have had a controlling influence on the
evolution of cell signaling pathways. Complexes associated with the bacterial
aspartate receptor, with eucaryotic tyrosine kinase receptors, with T-cell
receptors, and with focal contacts are examined together with proteins that serve
as adaptors, anchors, and scaffolds for signaling complexes. The importance of
diffusion in controlling the numbers and locations of signaling complexes is
discussed, as is the special role played by membranes in signaling pathways.
PMID- 9646863
TI - Spatio-temporal resolution of exocytosis from individual cells.
AB - Biophysical events involved in late stages of exocytosis occur at highly
localized areas of cells on millisecond and submillisecond time scales. Thus,
methodologies with high spatio-temporal resolution are required to achieve
measurements at individual secretory cells. Much has been learned about the
mechanisms and kinetics of vesicular release through analysis with the carbon
fiber microelectrode techniques amperometry and cyclic voltammetry. Coupling of
these techniques with other methods such as patch-clamp continues to reveal
details of the secretion process. It is now clear that extrusion of the vesicular
contents is a more complex process than previously believed. Vesicle-cell fusion,
revealed by cell capacitance measurements, is temporally dissociated from
secretion measured amperometrically. The stability imparted by interaction and
association of vesicle contents at rest results in a rate-limiting extrusion
process after full fusion. Furthermore, the presence of partial fusion events and
the occurrence of nonquantized release have been revealed with electrochemical
tools.
PMID- 9646864
TI - Minor groove-binding architectural proteins: structure, function, and DNA
recognition.
AB - To date, high-resolution structures have been solved for five different
architectural proteins complexed to their DNA target sites. These include TATA
box-binding protein, integration host factor (IHF), high mobility group I(Y)[HMG
I(Y)], and the HMG-box-containing proteins SRY and LEF-1. Each of these proteins
interacts with DNA exclusively through minor groove contacts and alters DNA
conformation. This paper reviews the structural features of these complexes and
the roles they play in facilitating assembly of higher-order protein-DNA
complexes and discusses elements that contribute to sequence-specific recognition
and conformational changes.
PMID- 9646865
TI - The structure and mechanism of protein phosphatases: insights into catalysis and
regulation.
AB - Eukaryotic protein phosphatases are structurally and functionally diverse enzymes
that are represented by three distinct gene families. Two of these, the PPP and
PPM families, dephosphorylate phosphoserine and phosphothreonine residues,
whereas the protein tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosine
amino acids. A subfamily of the PTPs, the dual-specificity phosphatases,
dephosphorylate all three phosphoamino acids. Within each family, the catalytic
domains are highly conserved, with functional diversity endowed by regulatory
domains and subunits. The protein Ser/Thr phosphatases are metalloenzymes and
dephosphorylate their substrates in a single reaction step using a metal
activated nucleophilic water molecule. In contrast, the PTPs catalyze
dephosphorylation by use of a cysteinyl-phosphate enzyme intermediate. The
crystal structures of a number of protein phosphatases have been determined,
enabling us to understand their catalytic mechanisms and the basis for substrate
recognition and to begin to provide insights into molecular mechanisms of protein
phosphatase regulation.
PMID- 9646866
TI - Biosensors in chemical separations.
AB - Identification of biomolecules in complex biological mixtures represents a major
challenge in biomedical, environmental, and chemical research today. Chemical
separations with traditional detection schemes such as absorption, fluorescence,
refractive index, conductivity, and electrochemistry have been the standards for
definitive identifications of many compounds. In many instances, however, the
complexity of the biomixture exceeds the resolution capability of chemical
separations. Biosensors based on molecular recognition can dramatically improve
the selectivity of and provide biologically relevant information about the
components. This review describes how coupling chemical separations with online
biosensors solves challenging problems in sample analysis by identifying
components that would not normally be detectable by either technique alone. This
review also presents examples and principles of combining chemical separations
with biosensor detection that uses living systems, whole cells, membrane
receptors, enzymes, and immunosensors.
PMID- 9646867
TI - Simulation of prokaryotic genetic circuits.
AB - Biochemical and genetic approaches have identified the molecular mechanisms of
many genetic reactions, particularly in bacteria. Now a comparably detailed
understanding is needed of how groupings of genes and related protein reactions
interact to orchestrate cellular functions over the cell cycle, to implement
preprogrammed cellular development, or to dynamically change a cell's processes
and structures in response to environmental signals. Simulations using realistic,
molecular-level models of genetic mechanisms and of signal transduction networks
are needed to analyze dynamic behavior of multigene systems, to predict behavior
of mutant circuits, and to identify the design principles applicable to design of
genetic regulatory circuits. When the underlying design rules for regulatory
circuits are understood, it will be far easier to recognize common circuit
motifs, to identify functions of individual proteins in regulation, and to
redesign circuits for altered functions.
PMID- 9646868
TI - DNA nanotechnology: novel DNA constructions.
AB - DNA nanotechnology entails the construction of specific geometrical and
topological targets from DNA. The goals include the use of DNA molecules to
scaffold the assembly of other molecules, particularly in periodic arrays, with
the objects of both crystal facilitation and memory-device construction. Many of
these products are based on branched DNA motifs. DNA molecules with the
connectivities of a cube and a truncated octahedron have been prepared. A solid
support methodology has been developed to construct DNA targets. DNA trefoil and
figure-8 knots have been made, predicated on the relationship between a
topological crossing and a half-turn of B-DNA or Z-DNA. The same basis has been
used to construct Borromean rings from DNA. An RNA knot has been used to
demonstrate an RNA topoisomerase activity. The desire to construct periodic
matter held together by DNA sticky ends has resulted in a search for stiff
components; DNA double crossover molecules appear to be the best candidates. It
appears that novel DNA motifs may be of use in the new field of DNA-based
computing.
PMID- 9646869
TI - Inhibitors of HIV-1 protease: a major success of structure-assisted drug design.
AB - Retroviral protease (PR) from the human immunodeficiency virus type 1 (HIV-1) was
identified over a decade ago as a potential target for structure-based drug
design. This effort was very successful. Four drugs are already approved, and
others are undergoing clinical trials. The techniques utilized in this remarkable
example of structure-assisted drug design included crystallography, NMR,
computational studies, and advanced chemical synthesis. The development of these
drugs is discussed in detail. Other approaches to designing HIV-1 PR inhibitors,
based on the concepts of symmetry and on the replacement of a water molecule that
had been found tetrahedrally coordinated between the enzyme and the inhibitors,
are also discussed. The emergence of drug-induced mutations of HIV-1 PR leads to
rapid loss of potency of the existing drugs and to the need to continue the
development process. The structural basis of drug resistance and the ways of
overcoming this phenomenon are mentioned.
PMID- 9646870
TI - Structure, dynamics, and function of chromatin in vitro.
AB - The substrates for the essential biological processes of transcription,
replication, recombination, DNA repair, and cell division are not naked DNA;
rather, they are protein-DNA complexes known as chromatin, in one or another
stage of a hierarchical series of compactions. These are exciting times for
students of chromatin. New studies provide incontrovertible evidence linking
chromatin structure to function. Exceptional progress has been made in studies of
the structure of chromatin subunits. Surprising new dynamic properties have been
discovered. And, much progress has been made in dissecting the functional roles
of specific chromatin proteins and domains. This review focuses on in vitro
studies of chromatin structure, dynamics, and function.
PMID- 9646871
TI - Cytochrome c oxidase: structure and spectroscopy.
AB - Cytochrome c oxidase, the terminal enzyme of the respiratory chains of
mitochondria and aerobic bacteria, catalyzes electron transfer from cytochrome c
to molecular oxygen, reducing the latter to water. Electron transfer is coupled
to proton translocation across the membrane, resulting in a proton and charge
gradient that is then employed by the F0F1-ATPase to synthesize ATP. Over the
last years, substantial progress has been made in our understanding of the
structure and function of this enzyme. Spectroscopic techniques such as EPR,
absorbance and resonance Raman spectroscopy, in combination with site-directed
mutagenesis work, have been successfully applied to elucidate the nature of the
cofactors and their ligands, to identify key residues involved in proton
transfer, and to gain insight into the catalytic cycle and the structures of its
intermediates. Recently, the crystal structures of a bacterial and a
mitochondrial cytochrome c oxidase have been determined. In this review, we
provide an overview of the crystal structures, summarize recent spectroscopic
work, and combine structural and spectroscopic data in discussing mechanistic
aspects of the enzyme. For the latter, we focus on the structure of the oxygen
intermediates, proton-transfer pathways, and the much-debated issue of how
electron transfer in the enzyme might be coupled to proton translocation.
PMID- 9646872
TI - The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics
of proteins.
AB - During the past thirty years, deuterium labeling has been used to improve the
resolution and sensitivity of protein NMR spectra used in a wide variety of
applications. Most recently, the combination of triple resonance experiments and
2H, 13C, 15N labeled samples has been critical to the solution structure
determination of several proteins with molecular weights on the order of 30 kDa.
Here we review the developments in isotopic labeling strategies, NMR pulse
sequences, and structure-determination protocols that have facilitated this
advance and hold promise for future NMR-based structural studies of even larger
systems. As well, we detail recent progress in the use of solution 2H NMR methods
to probe the dynamics of protein sidechains.
PMID- 9646873
TI - RNA recognition by RNP proteins during RNA processing.
AB - The ribonucleoprotein (RNP) domain is one of the most common eukaryotic protein
folds. Proteins containing RNP domains function in important steps of
posttranscriptional regulation of gene expression by directing the assembly of
multiprotein complexes on primary transcripts, mature mRNAs, and stable
ribonucleoprotein components of the RNA processing machinery. The diverse
functions performed by these proteins depend on their dual ability to recognize
RNA and to interact with other proteins, often utilizing specialized auxiliary
domains. Crystallographic and NMR structures of several RNP domains and a handful
of structures of RNA-protein complexes have begun to reveal the molecular basis
for RNP-RNA recognition.
PMID- 9646874
TI - On the characteristics of functional magnetic resonance imaging of the brain.
AB - In this review we discuss various recent topics that characterize functional
magnetic resonance imaging (fMRI). These topics include a brief description of
MRI image acquisition, how to cope with noise or signal fluctuation, the basis of
fMRI signal changes, and the relation of MRI signal to neuronal events. Several
observations of fMRI that show good correlation to the neurofunction are referred
to. Temporal characteristics of fMRI signals and examples of how the feature of
real time measurement is utilized are then described. The question of spatial
resolution of fMRI, which must be dictated by the vascular structure serving the
functional system, is discussed based on various fMRI observations. Finally, the
advantage of fMRI mapping is shown in a few examples. Reviewing the vast number
of recent fMRI application that have now been reported is beyond the scope of
this article.
PMID- 9646875
TI - Crystallographic structures of the hammerhead ribozyme: relationship to ribozyme
folding and catalysis.
AB - The hammerhead ribozyme is a small catalytic RNA that cleaves a target
phosphodiester bond in a reaction dependent on divalent metal ions. Crystal
structures of the hammerhead reveal the tertiary fold of an enzymatic "ground
state" of the molecule; however, they do not clarify the catalytic mechanism of
the ribozyme, presumably because a significant conformational rearrangement is
required to reach an enzymatic transition state. The structural domains seen in
the hammerhead can be related to sequence or structural motifs in transfer and
ribosomal RNAs, suggesting that they represent tertiary building blocks that will
be found in large, complex RNAs.
PMID- 9646876
TI - Pleckstrin homology domains: a common fold with diverse functions.
AB - Pleckstrin homology (PH) motifs are approximately 100 amino-acid residues long
and have been identified in nearly 100 different eukaryotic proteins, many of
which participate in cell signaling and cytoskeletal regulation. Despite minimal
sequence homology, the three-dimensional structures are remarkably conserved.
This review gives an overview of the PH domain architecture and examines the best
studied examples in an attempt to understand their function.
PMID- 9646877
TI - What do antidepressant effects on sleep tell us about pathways to treatment
response?
PMID- 9646878
TI - Comparative effects of nefazodone and fluoxetine on sleep in outpatients with
major depressive disorder.
AB - BACKGROUND: Sleep disturbances are common in major depressive disorder. In
previous open-label trials, nefazodone improved sleep continuity and increased
rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM
latency: in contrast, fluoxetine suppressed REM sleep. This study compared the
objective and subjective effects of nefazodone and fluoxetine on sleep. METHODS:
This paper reports combined results of three identical, multisite, randomized,
double-blind, 8-week, acute-phase trials comparing nefazodone (n = 64) with
fluoxetine (n = 61) in outpatients with nonpsychotic major depressive disorder
and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at
baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6,
and 8. RESULTS: Nefazodone and fluoxetine were equally effective in reducing
depressive symptoms; however, nefazodone differentially and progressively
increased (while fluoxetine reduced) sleep efficiency and reduced (while
fluoxetine increased) the number of awakenings in a linear fashion over the 8
week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed
REM sleep. Nefazodone significantly increased total REM sleep time. Clinical
evaluations of sleep quality were significantly improved with nefazodone compared
with fluoxetine. CONCLUSIONS: Nefazodone and fluoxetine were equally effective
antidepressants. Nefazodone was associated with normal objective, and clinician-
and patient-rated assessments of sleep when compared with fluoxetine. These
differential sleep EEG effects are consistent with the notion that nefazodone and
fluoxetine may have somewhat different modes and spectra of action.
PMID- 9646879
TI - Plasma corticotropin-releasing factor in depressive disorders.
AB - BACKGROUND: The aim of this work was to investigate alterations of plasma
corticotropin-releasing factor (CRF) levels in depressive states. We have also
measured plasma cortisol and corticotropin (ACTH) concentrations and examined
their correlation with the peripheral CRF values. METHODS: Thirty-six outpatients
from the psychiatric department of a Barcelona hospital who were diagnosed as
having major depressive disorder (n = 26) and dysthymic depressive disorder (n =
10) were studied. Among the major depressed patients, 10 suffered from severe
depressive disorder and 16 from mild or moderate depressive disorder. The
comparison group consisted of 17 healthy volunteers. Cortisol, ACTH, and CRF
concentrations were determined by iodine-125 radioimmunoassay; CRF measurements
were performed on C18 extracted samples. RESULTS: CRF and cortisol plasma
concentrations were significantly higher in major depression and dysthymia than
in the comparison group. The major depressed patients did not show significantly
different CRF and cortisol levels than the dysthymic. Severe major depressive
disorder exhibited significantly higher CRF plasma levels than the mild or
moderate episodes. Plasma cortisol and CRF concentrations correlated
significantly. CONCLUSIONS: The results obtained indicate that plasma CRF values
are altered in depressive disorders and suggest that these determinations could
be important for understanding the pathophysiology in affective illness.
PMID- 9646880
TI - Sleep electroencephalographic response to muscarinic and serotonin1A receptor
probes in patients with major depression and in normal controls.
AB - BACKGROUND: To test the hypothesis that depression is associated with an
increased ratio of cholinergic to serotonergic neurotransmission, we compared the
effects of pilocarpine, a muscarinic agonist, and ipsapirone, a serotonin (5
HT)1A agonist, on electroencephalographic (EEG) sleep in depressed and healthy
subjects. We hypothesized, adopting the reciprocal interaction model, that the
effects on REM sleep of these probes within the same individuals are negatively
correlated and unmask neurobiological changes in depression. METHODS:
Polysomnographic recordings were obtained in 12 unmedicated patients with a
current major depression and 12 normal controls. They received placebo,
pilocarpine 25 mg, or ipsapirone 10 mg (orally, 15 min before bedtime, after
premedication with the peripheral anticholinergic probanthine 30 mg, double
blind, counterbalanced) on three occasions. RESULTS: Pilocarpine shortened and
ipsapirone prolonged REM latency equally in both groups. These effects were not
correlated. Pilocarpine decreased slow-wave sleep and EEG delta power during the
first nonREM episode more in controls than in patients, and enhanced EEG sigma
power equally in both groups. Ipsapirone had no significant effects on EEG power.
CONCLUSION: These data do not support the postulate of muscarinic receptor up
regulation and 5-HT1A receptor down-regulation in depression. The significance of
blunted delta power suppression in patients following pilocarpine warrants
further investigations.
PMID- 9646881
TI - Structural and functional abnormalities in elderly patients clinically recovered
from early- and late-onset depression.
AB - BACKGROUND: Structural and functional brain changes have been described in
elderly patients with unipolar affective disorder. Changes appear to be more
marked in patients with late-onset depression, but the reversibility of such
changes after clinical recovery is not known. METHODS: Magnetic resonance
imaging, electroencephalography (EEG), and cognitive tests were performed in 23
elderly patients (mean age 66.5 years) clinically recovered from major
depression. Twelve had late-onset depression (first episode over 55 years of
age); 11 had early onset (first episode before 50 years). EEG and cognitive
testing were also performed on 15 control subjects. RESULTS: Patients with late
onset depression had larger third and lateral ventricles, increased ventricular
brain ratio, and greater frequency and severity of subcortical white matter
lesions than those with early onset. There was no difference between early- and
late-onset patients in EEG and cognitive measures, but compared with controls
patients showed significant changes in EEG evoked potentials and increased slow
wave activity, slowed reaction times, and global impairments in cognitive
function. CONCLUSIONS: These results suggest that structural changes are greater
in patients with late-onset depression, and that EEG and cognitive impairments
persist after recovery, regardless of age of onset of depression, and are
independent of structural changes.
PMID- 9646882
TI - Evidence for an allelic association between bipolar disorder and a Na+, K+
adenosine triphosphatase alpha subunit gene (ATP1A3).
AB - BACKGROUND: Disturbances in central nervous system Na+, K+ adenosine
triphosphatase (ATPase) activity have previously been proposed as being involved
in the pathophysiology of bipolar mood disorder. METHODS: We have examined one
particular alpha subunit of this enzyme for allelic association in a sample of 85
Irish bipolar patients and 85 matched controls. RESULTS: There was evidence for
an overall allelic association between the disease and a dinucleotide
polymorphism within the ATP1A3 gene (p = .022). Subjects were then analyzed on
the basis of a number of criteria, and the significance of the association
increased when cases were divided based on the nature of the first episode.
Patients who presented with a depressive episode first showed a significant
association (p = .001) with this polymorphism. CONCLUSIONS: The results presented
here provide preliminary evidence of an association between bipolar disorder and
an alpha subunit of Na+, K+ ATPase, the expression of which predominates in the
brain.
PMID- 9646883
TI - Effect of transcranial magnetic stimulation in posttraumatic stress disorder: a
preliminary study.
AB - BACKGROUND: Transcranial magnetic stimulation (TMS) has become, over the last few
years, a promising avenue for new research in affective disorders. In this study
we have evaluated the clinical effect of slow TMS on posttraumatic stress
disorder (PTSD) symptoms. METHODS: Ten PTSD patients were given one session of
slow TMS with 30 pulses of 1 m/sec each, 15 to each side of the motor cortex.
RESULTS: Symptoms of PTSD were assessed by using three psychological assessment
scales, at four different time points. In this first, pilot, open study, TMS was
found to be effective in lowering the core symptoms of PTSD: avoidance (as
measured by the Impact of Event Scale), anxiety, and somatization (as measured by
the Symptom Check List-90). A general clinical improvement was found (as measured
by the Clinical Global Impression scale); however, the effect was rather short
and transient. CONCLUSIONS: The present study showed TMS to be a safe and
tolerable intervention with possibly indications of therapeutic efficacy for PTSD
patients.
PMID- 9646884
TI - Plasma norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations and
severity of depression in combat posttraumatic stress disorder and major
depressive disorder.
AB - BACKGROUND: Catecholamines are thought to play a significant role in the
pathophysiology of posttraumatic stress disorder (PTSD), but findings in PTSD
have been discrepant. METHODS: To obtain more information about catecholamine
activity in PTSD, we sampled plasma norepinephrine (NE) and 3-methoxy-4
hydroxyphenylglycol (MHPG) concentrations over a 24-hour period in men with PTSD
(n = 15) and major depressive disorder (MDD) (n = 12), and nonpsychiatric
comparison subjects (n = 13), under unstimulated conditions. Chronobiological
analyses were performed to determine possible changes in the circadian and
ultradian release of these hormones. RESULTS: Significant group differences were
present for mean plasma NE levels (p = .03), but not MHPG. NE levels were
significantly associated with severity of depression in the PTSD group (p =
.002). Therefore, PTSD subjects were further subdivided into those with and
without a comorbid secondary depression. Increased NE levels were only present in
PTSD subjects who did not have a secondary depression. This study also found no
significant group differences on any of the chronobiological parameters.
CONCLUSIONS: The results clarify that increased NE levels in PTSD may be confined
to the subgroup of subjects who do not have comorbid depression, and as such, may
help resolve some of the discrepancies in the literature regarding basal
catecholamine activity.
PMID- 9646885
TI - Alprazolam reduces response to loud tones in panic disorder but not in
posttraumatic stress disorder.
AB - BACKGROUND: Posttraumatic stress disorder (PTSD) and panic disorder (PD) share
several clinical features, and theory postulates that phasic arousal is similarly
dysregulated in both. The modulation of phasic arousal can be probed by measuring
the effect of pharmacologic agents on auditory startle. METHODS: Eyeblink
electromyogram, heart rate, and skin conductance (SC) responses to 15 consecutive
presentations of 1000-Hz, 95-dB, zero rise-time pure tones were measured, before
and during treatment with alprazolam, in 9 PTSD and 9 PD patients. Concurrent
anxiety was assessed by the Hamilton Anxiety Rating Scale. RESULTS: The groups
did not differ in initial psychometric and physiological measures. Significant
decrease in anxiety was observed in both groups during treatment. A decrease in
response probability and a decrease in the SC responses were observed in PD, but
not in PTSD. CONCLUSIONS: The results may reflect a difference in the modulation
of phasic arousal between the disorders. They may also express an impaired
between-session habituation or contextual sensitization in PTSD.
PMID- 9646886
TI - Hypnotizability, pain threshold, and dissociative experiences.
AB - BACKGROUND: There may be an association between pain threshold, hypnotizability,
and dissociative experiences. The purpose of the present study was to examine
this association. METHODS: Forty-one healthy subjects were included in the study.
Pain thresholds were determined using a manual algometer. The Dissociative
Experiences Scale was administered to all subjects. Hypnotizability of the
subjects was assessed by the eye roll sign of the Hypnotic Induction Profile.
There were 14, 15, and 12 subjects in the Grade 1, 2, and 3 groups, respectively.
RESULTS: Highly hypnotizable subjects had lower pain thresholds and were more
likely to report dissociative experiences than the less hypnotizable subjects.
CONCLUSIONS: There is an association between pain threshold, hypnotizability, and
dissociative experiences. It may be suggested that dissociative and somatic
symptoms may be integrally linked and related to hypnotic suggestibility.
PMID- 9646887
TI - Attention-deficit hyperactivity disorder and the stress response.
AB - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a developmental
disorder whose three main symptoms are impulsiveness, inattention, and
hyperactivity. Researchers have proposed that the central deficit in ADHD is one
of poor response inhibition. The present studies were designed to look at the
functioning of the hypothalamic-pituitary-adrenal (HPA) axis in response to
mental stress in aggressive ADHD subjects participating in a longitudinal study
of various psychosocial treatments. METHODS: Pretest and posttest morning
salivary samples for cortisol determination were collected from subjects given a
battery of tests. RESULTS: The study shows that ADHD subjects who maintained
their diagnosis over the first year of the study had a blunted response to the
stressor in comparison to those ADHD subjects who no longer retained the disorder
1 year later. CONCLUSIONS: The data suggest that an impaired response to stress
may be a marker for the more developmentally persistent form of the disorder.
PMID- 9646888
TI - Selective serotonin reuptake inhibitor elimination half-lives: the long and the
short of it.
PMID- 9646889
TI - Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized
clinical trial.
AB - BACKGROUND: Recent reports describe discontinuation-emergent adverse events upon
cessation of selective serotonin reuptake inhibitors including dizziness,
insomnia, nervousness, nausea, and agitation. We hypothesized that interruption
of fluoxetine treatment would be associated with fewer discontinuation-emergent
adverse events than interruption of sertraline or paroxetine treatment, based on
fluoxetine's longer half-life. METHODS: In this 4-week study, 242 patients with
remitted depression receiving maintenance therapy with open-label fluoxetine,
sertraline, or paroxetine for 4-24 months had their maintenance therapy
interrupted with double-blind placebo substitution for 5-8 days. The Symptom
Questionnaire (SQ), the Discontinuation-Emergent Signs and Symptoms checklist,
the 28-item Hamilton Depression Rating Scale, and the Montgomery-Asberg
Depression Rating Scale were used to assess somatic distress and stability of
antidepressant response. RESULTS: Two hundred twenty patients (91%) completed the
study. Following interruption of therapy, fluoxetine-treated patients experienced
fewer discontinuation-emergent events than either sertraline-treated or
paroxetine-treated patients (p < .001). The mean SQ somatic symptom scale score
in fluoxetine-treated patients was significantly lower than that in sertraline
treated and paroxetine-treated patients (p < .001). Fluoxetine-treated patients
also experienced less reemergence of depressive symptoms than sertraline-treated
or paroxetine-treated patients (p < .001). CONCLUSIONS: Abrupt interruption of
antidepressant therapy for 5-8 days was associated with the emergence of new
somatic and psychological symptoms in patients treated with paroxetine and to a
lesser degree sertraline, with few symptoms seen with fluoxetine.
PMID- 9646890
TI - A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic
depressives.
AB - BACKGROUND: Recent studies have suggested that there may be a preferential
decrease of "nonpyramidal" neurons (NPs) in several corticolimbic regions of
schizophrenic (SZ) brain. The current study was undertaken to determine whether a
change in the density of pyramidal neurons (PNs) and NPs might be present in the
hippocampal formation (HIPP) of SZ brain. METHODS: A spatial counting approach in
which the location of each and every PN and NP in the stratum pyramidale of
sectors CA1-4 was applied to 11 normal control (CONs) and 10 SZs matched for age
and postmortem interval, as well as 4 manic depressive (MD) subjects matched for
age. RESULTS: The data indicate that the CONs had approximately 10-20 times as
many PNs than NPs in the various HIPP subfields. When the CON data were compared
to those for the SZs, both the total number and density of PNs were found to be
similar in all four sectors, while NPs were found to be selectively reduced by
approximately 40% in CA2 of the SZ group. When the data were broken down
according to patients with and without neuroleptic exposure, drug-free SZs showed
a significant reduction in the density of NPs in CA2. The 4 MD cases both with
and without neuroleptic exposure also showed a similar reduction of NPs in sector
CA2. CONCLUSIONS: Taken together, the results of this study suggest that there
may be a highly selective decrease in the number of NPs in sector CA2 that could
play a contributory role in the pathophysiology of the major psychoses.
PMID- 9646891
TI - Nicotinic receptor desensitization and sensory gating deficits in schizophrenia.
AB - BACKGROUND: Nicotinic receptor dysfunction is a possible mechanism of the
abnormal sensory gating observed in schizophrenia with the P50 auditory event
related potential. Although nicotinic receptors normally desensitize after
activation by acetylcholine or nicotine, pathologically increased desensitization
might cause receptor dysfunction in schizophrenia. To examine this possibility,
central cholinergic neuronal activity was diminished by allowing schizophrenic
patients to sleep briefly, after which they experienced a transient period of
normal P50 gating, consistent with receptor resensitization during the absence of
cholinergic stimulation. A critical test of the mechanism is whether this
resensitization is blocked by concurrent administration of nicotine, which would
provide continuous receptor stimulation. METHODS: Six schizophrenic patients
repeated the sleep experiment during nicotine exposure from a dermal patch, in a
double-blind, placebo-controlled design. RESULTS: The normalization of P50 gating
immediately postsleep was replicated in the placebo arm, but this effect was
decreased in all six patients during exposure to nicotine. CONCLUSIONS: The
results suggest that nicotinic receptor desensitization is responsible for the
loss of P50 gating in schizophrenia.
PMID- 9646892
TI - Factor structure and clinical validity of competing models of positive symptoms
in schizophrenia.
AB - BACKGROUND: The factor structure of four competing models of positive symptoms
and their clinical validity was studied in a sample of 253 schizophrenia
inpatients. METHODS: The following models were tested using confirmatory factor
analysis: a one-dimension severity model, a two-dimension model comprising a
psychosis factor and a disorganization factor, a four-dimension model based on
the Scale for the Assessment of Positive Symptoms (SAPS) structure in subscales,
and a five-dimension model derived from the previous one by further
differentiating Schneiderian delusions from non-Schneiderian ones. RESULTS: More
complex multifactorial models fit the data better than simpler models. The five
dimension model was the best adjusted (goodness of fit index = .844, nonnormed
fit index = .812, normed fit index = .728). Whereas the one-dimension model did
not display significant association with the clinical variables, multidimensional
models were related to age at onset and illness severity. The two-dimension model
captured well the clinical correlates of the more complex models. CONCLUSION:
None of the tested models showed good fit to the data. The one-dimension model
displayed both poor factor validity and poor external validity; therefore,
research relying on the SAPS total score may reach misleading conclusions.
PMID- 9646893
TI - P300 and the thought disorder factor extracted by factor-analytic procedures in
schizophrenia.
AB - BACKGROUND: In order to clarify the clinical significance of P300 as a biologic
marker that can reflect schizophrenic symptomatology, many previous studies have
evaluated the relationship of P300 with the symptoms on the basis of a
positive/negative dichotomy, but yielded inconsistent conclusions. Such a
dichotomy has been criticized as being too reductionistic. Recently, most studies
with factor-analytic procedures have extracted some symptom factors outside this
dichotomy. Therefore, it is important to examine associations of P300 with the
symptom factors extracted by these statistical analyses. METHODS: In the present
study, the amplitudes of P300 were measured by using an auditory oddball paradigm
for 73 schizophrenics whose psychopathology was assessed with the Positive and
Negative Syndrome Scale (PANSS). RESULTS: The principal component analysis of the
PANSS items revealed five factors labeled the thought disorder, negative,
hostile/excitable, delusional/hallucinatory, and depressive factors. The score
for the thought disorder factor correlated negatively with the amplitude of P300
recorded at Pz T5, and T6, but that for the other factors did not. CONCLUSIONS:
These findings suggest that the reduction of P300 amplitudes recorded at the
midline parietal and bilateral temporoparietal regions may be one of the
electrophysiologic indices representing the thought disorder clinically observed
in schizophrenia.
PMID- 9646894
TI - Slow-wave sleep and ventricular size: a comparative study in schizophrenia and
major depression.
AB - BACKGROUND: A slow-wave sleep (SWS) deficit and a shortened rapid eye movement
(REM) sleep latency are commonly described in schizophrenia and depression. In
addition, a close association between ventricular system measurements and SWS are
reported in both disorders; however, a comparative, combined polysomnographic and
computed tomographic investigation is lacking. METHODS: In the present post hoc
study we analyzed the electroencephalographic sleep pattern and the ventricular
brain ratio (VBR) of 14 drug-naive schizophrenic patients and of 14 depressed
patients who were drug-free for a sufficient time period. RESULTS: Whereas the
depressives showed the often described SWS and REM sleep changes, these
measurements were quite normal in the schizophrenics. The VBR values were similar
in both patient groups and exceeded in 71% of the schizophrenics and in 50% of
the depressives the cutoff point of a "normal" VBR value. A close association
between SWS and VBR was found in the depressives but not in the schizophrenics.
CONCLUSIONS: The results of the present study of drug-naive schizophrenic
patients and of depressed patients indicate only a minor overlap between the
pathophysiological changes observed in both disorders. Therefore, the present
investigation adds evidence for the assumption that schizophrenia and depression
are etiopathogenetically distinct entities, rather than representing points on a
continuum of liability.
PMID- 9646895
TI - Electroacupuncture: mechanisms and clinical application.
AB - Acupuncture is an ancient Chinese method to treat diseases and relieve pain. We
have conducted a series of studies to examine the mechanisms of this ancient
method for pain relief. This article reviews some of our major findings. Our
studies showed that acupuncture produces analgesic effect and that
electroacupuncture (EA) is more effective than manual acupuncture. Furthermore,
electrical stimulation via skin patch electrodes is as effective as EA. The
induction and recovering profiles of acupuncture analgesia suggest the
involvement of humoral factors. This notion was supported by cross-perfusion
experiments in which acupuncture-induced analgesic effect was transferred from
the donor rabbit to the recipient rabbit when the cerebrospinal fluid (CSF) was
transferred. The prevention of EA-induced analgesia by naloxone and by antiserum
against endorphins suggests that endorphins are involved. More recent work
demonstrated the release of endorphins into CSF following EA. In addition, low
frequency (2 Hz) and high frequency (100 Hz) of EA selectively induces the
release of enkephalins and dynorphins in both experimental animals and humans.
Clinical studies suggesting its effectiveness for the treatment of various types
of pain, depression, anxiety, spinally induced muscle spasm, stroke,
gastrointestinal disorders, and drug addiction were also discussed.
PMID- 9646896
TI - Psychotic symptoms and apolipoprotein E genotypes in an elderly population.
AB - BACKGROUND: Psychotic symptoms have been found to be more common in demented
elderly persons. Genetic variation in the apolipoprotein E (APOE) gene is
reported to be associated with variation in the risk of Alzheimer's dementia.
This study reports on variables associated with psychotic symptoms including
APOE, in demented and nondemented elderly persons. METHODS: A population of 668
elderly persons was examined. APOE genotype was available in 309 individuals.
RESULTS: Psychotic symptoms were found to be associated with dementia, a previous
psychiatric history, female gender, being less educated, disability in daily
living and institutionalisation. In the nondemented group, psychotic symptoms
were equally common in subjects with or without the epsilon 4 present. In the
demented subjects, psychotic symptoms were slightly more common, although not
significant, in subjects without the epsilon 4 genotype. CONCLUSIONS: There was
no statistical significant difference in APOE genotype between subjects with and
without psychotic symptoms, stratified by dementic diagnosis.
PMID- 9646897
TI - Schizophrenia and impaired homocysteine metabolism: a possible association.
AB - BACKGROUND: An increased risk of both schizophrenia and neural tube defects was
observed in a birth cohort exposed to famine during early gestation. Neural tube
defects have been related to a folate-sensitive genetic defect in homocysteine
metabolism. If this were also true for schizophrenia, then cases with low folate
(LF)--and only these cases--should have increased homocysteine levels compared
with controls. METHODS: We compared homocysteine levels of schizophrenia cases
and normal controls with low folate (LF) and without low folate (non-LF). Low
folate was defined by the bottom tertile for controls. RESULTS: In the LF group
(6 cases, 8 controls), mean homocysteine was 10.7 microM in cases compared with
7.7 microM in controls (p = .03). In the non-LF group (11 cases, 16 controls)
mean homocysteine did not differ for cases and controls. CONCLUSIONS: These pilot
data are compatible with the hypothesis that a folate-sensitive defect in
homocysteine metabolism contributes to cases of schizophrenia.
PMID- 9646898
TI - Analysing the redox status of plant tissues by FSCE.
PMID- 9646899
TI - Fast narrow-bore HPLC-DAD analysis of biologically active thiosulfinates obtained
without solvent from wild Allium species.
PMID- 9646900
TI - Screening of post-explosive samples for common high explosive components by MECC.
PMID- 9646902
TI - Highly efficient separation of amines by electrokinetic chromatography using
resorcarene-octacarboxylic acids as pseudo-stationary phases.
PMID- 9646901
TI - In vivo/in vitro microdialysis coupled to capillary LC-LIF.
PMID- 9646903
TI - Advantages in the analysis of UDP-sugars by capillary electrophoresis-comparison
of the conventional HPLC method with two new capillary electrophoretic micro
procedures.
AB - Two different capillary electrophoretic separation modes for the analysis of UDP
sugars have been tested. In comparison to the traditionally used HPLC method the
micellar electrokinetic capillary chromatography (MECC) as well as the capillary
zone electrophoresis (CZE) results in an improvement of the separation profile
and the speed of the analysis.
PMID- 9646904
TI - Recent applications of polysaccharide-type chiral stationary phases for the
enantioselective analysis of chiral drugs with one and two stereogenic centers.
PMID- 9646905
TI - Capillary electrophoresis and capillary chromatography: theoretical analogies and
practical differences.
PMID- 9646906
TI - Utilisation of HPLC to substitute preparative column chromatography for the
quality survey of frying fats and oils.
PMID- 9646907
TI - Conducting polymer based potentiometric detection applied to the determination of
organic acids with narrow-bore LC systems.
PMID- 9646908
TI - Drug analysis by capillary electrophoretic methods.
PMID- 9646909
TI - Determination of benzalkonium chloride in drug formulations by capillary
electrophoresis (CE).
AB - A Capillary Electrophoresis method was developed and applied successfully to test
the quality of different drug formulations for release and stability studies. In
the method an uncoated fused-silica capillary was employed containing a
phosphoric acid buffer electrolyte which was brought to pH by triethylamine. The
benzalkonium chlorides (BAC-C12 and BAC-C14) present in the standard were
completely separated from each other and from the peaks of the main compound.
Performance results of the method in terms of system repeatability, precision and
accuracy are discussed.
PMID- 9646910
TI - Enantioseparation of acidic drugs by capillary electrophoresis using dual systems
with mixtures of charged and neutral cyclodextrins.
PMID- 9646911
TI - HPTLC assay of cephalexin and cefaclor in pharmaceuticals.
AB - A simple and reliable HPTLC method for the simultaneous determination of
cephalexin and cefaclor is developed and validated. The methanol-ethyl acetate
acetone-water (5:2.5:2.5:1.5 v/v/v/v) solvent system is used for the quantitative
evaluation of chromatograms. The chromatographic zones, corresponding to the
spots of cephalexin and cefaclor on the silica gel plates, are scanned in the
reflectance/absorbance mode at 265 nm. The method is found to be reproducible and
convenient for the quantitative analysis of cephalexin and cefaclor in its dosage
forms.
PMID- 9646912
TI - Capillary electrochromatography (CEC): methodology and applications.
PMID- 9646913
TI - Determination of aggregates in a formulated recombinant fusion protein by SDS
capillary electrophoresis.
PMID- 9646914
TI - Effect of the particle size in capillary electrochromatography.
PMID- 9646915
TI - Comparison of mass spectrometry interfacing techniques for microcolumn liquid
separations.
PMID- 9646916
TI - Evaluation of CZE for studying protein binding of aluminium in human serum.
PMID- 9646917
TI - Determination of ascorbic acid in nanolitre samples by means of capillary batch
injection analysis.
AB - Capillary batch injection analysis (CBIA) is applied to the determination of
ascorbic acid in nanolitre samples at neutral pH. It is demonstrated that pulsed
amperometric detection is superior to constant-potential amperometric detection
with respect to signal stability. The calibration plot is linear within the
studied concentration range between 0.5 mM and 5 mM and the reproducibility is
characterized by a relative standard deviation of 0.80% for 10 successive
injections of 188 nL of 3.5 mM ascorbic acid. The attainable sample throughput is
up to 500 per hour.
PMID- 9646918
TI - Application of a new PVC-based ion-selective electrode for surfactant detection
in microflow systems.
PMID- 9646919
TI - Separation of tetracycline and its related substances: comparison of liquid
chromatography, capillary electrophoresis and capillary electrochromatography.
PMID- 9646920
TI - Comparison of capillary liquid chromatography vs capillary electrophoresis, using
the same detector.
PMID- 9646921
TI - High temperature and temperature programming in capillary HPLC.
PMID- 9646922
TI - Miniaturized thermal lens device for capillary electrophoresis.
AB - In this paper we will report on the combination of a miniaturized fiber optic
modified photothermal sensor (size 2 x 2 x 2 cm) to capillary electrophoresis
(CE) as detection device. The properties and the performances of the thermal lens
detector, based on a double beam absorption scheme, were studied in a capillary
electrophoresis system with different types of toxic pollutants, e.g. pesticides.
A tunable Argon ion laser, which emits between 364 and 514 nm, was adapted to a
commercial injection and high voltage CE system. The miniaturization of the
thermal lens detector head with optical waveguides allows the combination with
typical CE systems, therefore pesticides in microliter volumes can be treated.
The detector performance is demonstrated with the monitoring of pesticides in
capillaries with various diameter. The limit of detection is one of two orders of
magnitude better than conventional absorption detector.
PMID- 9646923
TI - On-line coupling of capillary HPLC with 1H NMR spectroscopy.
PMID- 9646924
TI - Narrow-bore liquid chromatography coupled to chemiluminescence detection for the
analysis of pharmaceutical preparations containing hydrochlorothiazide and
captopril.
PMID- 9646925
TI - Flow-injection analysis of hydrochlorothiazide applying sensitised
chemiluminescence detection: optimisation in view of narrow-bore HPLC.
PMID- 9646926
TI - Narrow-bore reversed-phase liquid chromatography of metronidazole benzoate and
its hydrolysis products.
PMID- 9646927
TI - Comparative narrow-bore high-performance liquid chromatographic determination of
ketoprofen in horse plasma.
PMID- 9646928
TI - Narrow-bore HPLC analysis of isoflavonoid aglycones and their O- and C-glycosides
from Pueraria lobata.
PMID- 9646929
TI - Trends towards sensitive detection in capillary electrophoresis: an overview of
some recent developments.
PMID- 9646930
TI - A first and straightforward approach to detection limits for narrow-bore HPLC and
CE.
AB - Two methodologies have been proposed for a simple statistical estimation of the
detection limits in microbore-HPLC and CE techniques. Due to the impossibility to
measure the blank, by using the extrapolated or approximated expressions it is
possible to obtain a straightforward approach of the detection limits from the
study of the residuals of the calibration data set, avoiding tedious treatment of
the signals. The utility of these expressions has been checked on the data from
an experimental microbore HPLC system.
PMID- 9646931
TI - Chiral separation of antisense oligonucleotides: a feasibility study.
PMID- 9646932
TI - Advantages of capillary electrophoresis for determination of choline in
pharmaceutical preparations.
AB - Assay of choline in pharmaceutical preparations was realized by capillary zone
electrophoresis (CZE) coupled with indirect UV detection. The suitability of
several background electrolytes was investigated to optimize the separation of
choline from other components such as amino acids, betaine and cations. Final
operating conditions were as follows: a 75 microns x 50 cm uncoated fused-silica
capillary with an electrolyte consisting of 5 mM creatinine pH 3.2, a voltage of
25 kV, a temperature of 25 degrees C and an UV detection at 210 nm. Choline
migrates in less than 5 min and full selectivity vs other analytes was achieved.
Validation data compared with those obtained with HPLC demonstrated the interest
of CZE.
PMID- 9646933
TI - Use of capillary electrophoresis for the characterization of human serum albumin
heterogeneity.
AB - Human serum albumin (HSA) is used in large amounts as an excipient in many
biopharmaceutical formulation to prevent loss of the active ingredient through
adsorption and/or degradation. Traditionally, iso-electric focusing has been used
to demonstrate charge heterogeneity in HSA preparations. In an effort to develop
new methods for the analysis of formulation components, a capillary zone
electrophoresis method was developed for the analysis of HSA. Under initial
separation conditions using untreated silica capillaries and 20 mM sodium
phosphate, pH 6.0 as electrophoretic buffer, HSA migrated as a single peak.
Addition of 1,4-diaminobutane allowed separation of several components which
could be further resolved by varying the buffer pH. Optimal separation conditions
were attained at 5 mM 1,4-diaminobutane and pH 8.5. The reproducibility of the
separation conditions was verified by using capillaries from a different
manufacturer. A comparative analysis of HSA preparations from different
manufacturers provided evidence that the method may be used to qualitatively
differentiate individual preparations. The analysis of rhEPO formulations,
composed largely of HSA, showed levels of heterogeneity comparable to that of HSA
preparations. Electrospray ionisation mass spectrometry (ESA-MS) was used as an
independent method to confirm the heterogeneous nature of HSA.
PMID- 9646934
TI - A genetic basis for neuroendocrine-immune interactions.
AB - Psychoneuroimmunology is an exciting, complex field that elucidates interactions
among the nervous, endocrine, and immune systems. The contribution of
psychosocial factors and behavioral processes to these interactions has been the
focus of numerous studies designed to investigate the intricate pathways that are
involved in the "mind-body connection." In addition, the effects of this
connection on the development and progression of various disease conditions are
of considerable interest. Although efforts have been made to identify the
cellular and molecular mechanisms underlying these relationships, the impact of
genetic makeup on the communication among these systems has yet to be fully
realized. The development of sophisticated genetic analytical methods and gene
mapping techniques now provide the "tools" to determine the influence of genetics
on behavior-neuroendocrine-immune interactions--an area of study that may
represent the next frontier in psychoneuroimmunology.
PMID- 9646935
TI - Attenuation of behavioral abnormalities in autoimmune mice by chronic soluble
interferon-gamma receptor treatment.
AB - NZB x NZW F1 hybrid (B/W) mice develop altered behavior in the elevated plus maze
and novel object tasks between 6 and 12 weeks of age in parallel with lupus-like
autoimmune disease. To confirm the relationship between disease progression and
development of behavioral abnormalities, B/W and nonautoimmune NZW mice received
chronic treatment with a soluble IFN gamma receptor (sIFN gamma R), a treatment
known to retard autoimmune disease progression, or vehicle, beginning at 6 weeks
of age. After 6 weeks of treatment, elevated plus maze and novel object testing
revealed that although sIFN gamma R treated B/W mice still differed from NZW
mice, chronic sIFN gamma R treatment significantly retarded the development of
behavioral abnormalities in the B/W mice, while the NZW mice were not affected by
this treatment. sIFN gamma R treated B/W mice were more active in both the plus
maze and novel object tasks, and displayed less plus maze anxiety behavior and
more exploratory activity in the novel object task compared to vehicle treated
B/W mice. To clarify the role of acute action of the sIFN gamma R on the elevated
IFN gamma levels of B/W mice, a second experiment examined the effects of a
single injection of sIFN gamma R on B/W and NZW mice. Unlike chronic treatment,
acute treatment with the same dose of sIFN gamma R did not affect plus maze or
novel object behavior in 12-week-old mice. These results add to the growing
evidence that lupus-associated behavioral abnormalities are a direct effect of
the autoimmune disease.
PMID- 9646936
TI - Localization of corticotropin-releasing factor in primary and secondary lymphoid
organs of the rat.
AB - Cells of the immune system produce a variety of neuropeptides or peptide
hormones, either constitutively or upon induction, and possess specific
neuropeptide receptors that display ligand-receptor interactions similar to those
described in the central nervous system (CNS). These findings suggest that
specific subsets of lymphoid cells can produce and respond to peptides previously
thought to be principally neural mediators. Recently, corticotropin releasing
factor (CRF) mRNA was detected in the rat thymus and spleen, although the cells
that synthesize CRF were not identified. We examined the localization of CRF and
its mRNA in the rat spleen, thymus, and mesenteric lymph nodes using
immunocytochemistry (ICC) and in situ hybridization (ISH), respectively.
Immunoreactive CRF was present in cells in the marginal zone and red pulp of the
spleen, in connective tissue septa and the subcapsular region of the thymus, and
in the medullary cords and sinuses of the mesenteric lymph nodes. Dual ICC/ISH
for CRF and its mRNA, respectively, demonstrated CRF mRNA over CRF-immunoreactive
cells, suggesting CRF synthesis. Double-label ICC for CRF and markers for
specific immunocyte subsets suggest that CRF+ cells in the spleen and thymus are
macrophages. CRF+ cells in primary and secondary lymphoid organs reside in
compartments that are innervated by sympathetic nerves, and some cells appears to
be contacted by noradrenergic sympathetic nerve fibers, suggesting that CRF
release may be influenced by the sympathetic nervous system, as it is in the
hypothalamo-pituitary-adrenal axis. The presence of CRF in organs of the immune
system suggests that this neuropeptide may modulate immune functions after
paracrine release.
PMID- 9646937
TI - Increased number of mast cells in the central nervous system of adult male mice
following chronic subordination stress.
AB - Mast cells (MCs) are amine-storing cells with heterogeneous histological,
biochemical, and functional properties. They are found in connective tissue as
well as in the peripheral and central nervous system (CNS) of many mammalian
species. In this study we investigated whether the distribution of MCs in the CNS
of adult male CD-1 mice was modified following repeated defeat stress.
Experimental subjects underwent a 3-week period of fighting encounters with a
highly aggressive resident. On the test day they were divided into three groups:
(a) paired with the resident for 20 min; (b) placed in a cage containing the
soiled bedding of the resident for 20 min; (c) placed in a cage with clean
sawdust for 20 min. Results show that previous defeat stress increases the number
of MCs in the thalamus, habenula, and hypothalamus of subjects exposed to a
fighting opponent or to a clean cage, compared to subjects placed in a cage with
the bedding of the opponent or to a group-housed, nondefeated control. These
results, together with previous reports in birds and rodents, suggest that MCs
have a wider role than previously expected and might be involved in the
behavioral response to highly relevant psychosocial stimuli.
PMID- 9646938
TI - Chronic varied stress modulates experimental autoimmune encephalomyelitis in
Wistar rats.
AB - Stress disturbs homeostasis by altering the equilibrium of various hormones which
have a significant impact on immune responses. Few studies have examined the
influence of stressors on autoimmune disease in animal models. In our work, we
studied the effects of long-term exposure (14 days) to chronic varied stress
(CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar
rats. We studied whether the exposure to CVS before or after the immune challenge
would correlate with differences in the clinical course of the disease. We also
examined whether the CVS would modulate the magnitude of the cellular or the
humoral immune response. We observed opposite effects on the clinical signs in
animals stressed before or after the immune challenge. The clinical signs of the
disease were attenuated in animals stressed before but not after the immune
challenge. Relationships were found in the modulation of the clinical severity
related to the time of exposure to the CVS, the histological alterations and the
proliferative results. Stressed animals with milder clinical signs presented an
exacerbated humoral response against myelin antigens while stressed animals with
more severe clinical symptoms exhibited a significantly diminished one. Besides,
we detected the presence of specific IgG1 associated with the exposure to CVS
before the induction of EAE. Our results show that, depending on the timing of
the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a
more pronounced humoral or cellular profile of the response.
PMID- 9646939
TI - Differential effects of NMDA-induced lesions into the insular cortex and amygdala
on the acquisition and evocation of conditioned immunosuppression.
AB - It has been established that the insular cortex (IC) mediates conditioned taste
aversion, and recently we have demonstrated that lesions of this structure
disrupt the acquisition of conditioned immunosuppression (CIS). The IC is
functionally and reciprocally interconnected with the amygdala (AM) which has
been suggested to be involved in neural-immune interactions. The aim of this work
was to test the effects of NMDA-induced lesions in either the IC or AM in the
acquisition (lesions made before conditioning) and evocation (lesions made after
conditioning) of a conditioned immunosuppression task, obtained by one single
pairing of saccharin taste and the immunosuppressive drug, cyclophosphamide. AM
and IC lesioned rats were separated into four groups: the first two received
lesions before and the other two were lesioned after the acquisition of
conditioned immunosuppression. Twenty days after conditioning, animals were
reexposed to saccharin and immunized with ovalbumin. After immunization, blood
samples were taken, and analyzed by ELISA. The results showed that IC lesions
disrupted the acquisition and evocation of CTA and CIS. Conversely, AM lesions
disrupted only the acquisition of CIS. These data suggest that the IC is involved
in the neural mechanisms underlying the acquisition and evocation of conditioned
immunosuppression, and the amygdala could be important in mediating the input of
the immune information necessary for the acquisition of conditioned
immunosuppression.
PMID- 9646940
TI - Functional homodimeric glycoprotein hormones: implications for hormone action and
evolution.
AB - BACKGROUND: Human chorionic gonadotropin (hCG), lutropin, follitropin, and
thyrotropin act as alpha beta heterodimers to control reproduction and thyroid
function. The alpha and beta subunits of these proteins are divided into three
loops (alpha 1,alpha 2,alpha 3; beta 1,beta 2,beta 3) by cysteine knots and the
heterodimer is stabilized by 20 beta-subunit residues wrapped around alpha 2 like
a seatbelt. Understanding how these hormones interact with their receptors, a
matter of considerable dispute, would facilitate design of pro- and anti
fertility agents. RESULTS: By swapping alpha 2 for beta 2 and vice versa and, in
some cases, adding an amino-terminal coiled-coil dimerization domain, we prepared
homodimeric analogs that have the conformation found in each 'half' of hCG.
Homodimers containing loops beta 1,alpha 2,beta 3 and none, part, or all of the
seatbelt stimulated signal transduction to the same extent as hCG, albeit with
lower potency. Those containing alpha 1,beta 2,alpha 3 were inactive.
CONCLUSIONS: The activities of homodimers containing the beta 1,alpha 2,beta 3
groove exceed those of other minimized analogs more than 100-1000-fold,
suggesting this portion of the hormone forms the major receptor contact. The
discovery that glycoprotein hormone heterodimers can be converted to functional
homodimers supports the proposal that this protein family evolved from an active
homodimeric ancestor by gene duplication and acquisition of mutations to loop 2
that prevent homodimerization. This approach to protein minimization should be
applicable to other proteins composed of architecturally related subunits,
including those that might have arisen by gene duplication.
PMID- 9646941
TI - Synergistic activation of soluble guanylate cyclase by YC-1 and carbon monoxide:
implications for the role of cleavage of the iron-histidine bond during
activation by nitric oxide.
AB - BACKGROUND: Nitric oxide (.NO) is used in biology as both an intercellular
signaling agent and a cytotoxic agent. In signaling, submicromolar quantities of
.NO stimulate the soluble isoform of guanylate cyclase (sGC) in the receptor
cell. .NO increases the Vmax of this heterodimeric hemoprotein up to 400-fold by
interacting with the heme moiety of sGC to form a 5-coordinate complex. Carbon
monoxide (CO) binds to the heme to form a 6-coordinate complex, but only
activates the enzyme 5-fold, YC-1 is a recently discovered compound that relaxes
vascular smooth muscle by stimulating sGC. RESULTS: In the presence of YC-1, CO
activates sGC to the same specific activity as attained with .NO. YC-1 did not
affect the NO-stimulated activity. The on-rate (kon) and off-rate (koff) of CO
for binding to sGC in the presence of YC-1 were determined by stopped-flow
spectrophotometry. Neither the kon nor the koff varied from values previously
obtained in the absence of YC-1, indicating that YC-1 has no effect on the
affinity of CO for the heme. In the presence of YC-1, the visible spectrum of the
sGC-CO complex has a Soret peak at 423 nm, indicating the complex is 6
coordinate. CONCLUSIONS: YC-1 has no effect on the affinity of CO for the heme of
sGC. In the presence of YC-1, maximal activation of sGC by CO is achieved by
formation of a 6-coordinate complex between CO and the heme indicating that
cleavage of the Fe-His bond is not required for maximal activation of sGC.
PMID- 9646942
TI - DNA damage induced via independent generation of the radical resulting from
formal hydrogen atom abstraction from the C1'-position of a nucleotide.
AB - BACKGROUND: Deoxyribonucleotide radicals resulting from formal C1'-hydrogen atom
abstraction are important reactive intermediates in a variety of DNA-damage
processes. The reactivity of these radicals can be affected by the agents that
generate them and the environment in which they are produced. As an initial step
in determining the factors that control the reactivity of these important radical
species, we developed a mild method for their generation at a defined site within
a biopolymer. RESULTS: Irradiation of oligonucleotides containing a photolabile
nucleotide produced C1'-DNA radicals. In the absence of potential reactants other
than O2, approximately 90% of the damage events involve formation of alkaline
labile lesions, with the remainder resulting in direct strand breaks. The ratio
of alkaline-labile lesions to direct strand breaks (approximately 9:1) is
independent of whether the radical is generated in single-stranded DNA or double
stranded DNA. Strand damage is almost completely quenched under anaerobic
conditions in the presence of low thiol concentrations. Competition studies with
O2 indicate that the trapping rate of C1'-DNA radicals by beta-mercaptoethanol is
approximately 1.1 x 10(7) M-1s-1. CONCLUSIONS: The mild generation of the C1'-DNA
radical in the absence of exogenous oxidants makes it possible to examine their
intrinsic reactivity. In the absence of other reactants, the formation of direct
strand breaks from C1'-radicals is, at most, a minor pathway. Competition studies
between beta-mercaptoethanol and O2 indicate that significantly higher thiol
concentrations than those in vivo or some means of increasing the effective thiol
concentration near DNA are needed for these reagents to prevent the formation of
DNA lesions arising from the C1'-radical under aerobic conditions.
PMID- 9646943
TI - Nitrite and nitrate analyses: a clinical biochemistry perspective.
AB - OBJECTIVE: To review the assays available for measurement of nitrite and nitrate
ions in body fluids and their clinical applications. DESIGN AND METHODS:
Literature searches were done of Medline and Current Contents to November 1997.
RESULTS: The influence of dietary nitrite and nitrate on the concentrations of
these ions in various body fluids is reviewed. An overview is presented of the
metabolism of nitric oxide (which is converted to nitrite and nitrate). Methods
for measurement of the ions are reviewed. Reference values are summarized and the
changes reported in various clinical conditions. These include: infection,
gastroenterological conditions, hypertension, renal and cardiac disease,
inflammatory diseases, transplant rejection, diseases of the central nervous
system, and others. Possible effects of environmental nitrite and nitrate on
disease incidence are reviewed. CONCLUSIONS: Most studies of changes in human
disease have been descriptive. Diagnostic utility is limited because the
concentrations in a significant proportion of affected individuals overlap with
those in controls. Changes in concentration may also be caused by diet, outside
the clinical investigational setting. The role of nitrite and nitrate assays
(alongside direct measurements of nitric oxide in breath) may be restricted to
the monitoring of disease progression, or response to therapy in individual
patients or subgroups. Associations between disease incidence and drinking water
nitrate content are controversial (except for methemoglobinemia in infants).
PMID- 9646944
TI - The place of electron spin resonance methods in the detection of oxidative stress
in type 2 diabetes with poor glycemic control.
AB - OBJECTIVE: Chronic production of reactive oxygen species (ROS) and/or deficiency
in the antioxidant defense system are observed in non-insulin-dependent diabetes
mellitus (NIDDM) patients. As an adjunct to the usual indirect parameters for
evaluating oxidative stress, we assessed the feasibility of oxyradicals detection
in venous blood by electron spin resonance spectroscopy (ESR). Detection of the
ascorbate pool was also performed using the validated ESR analysis of the
ascorbyl free radial (AFR)-dimethyl sulfoxide (DMSO) complex. METHODS AND
RESULTS: Plasma lipoperoxidation was characterized by higher levels of total MDA
(1.50 +/- 0.08 nmol/L), lower levels of GSH (0.54 +/- 0.02 mmol/L) and of vitamin
A (2.13 +/- 0.52 mumol/L) in the NIDDM group than in the controls (0.75 +/- 0.05
nmol/L, 0.90 +/- 0.05 mmol/L, 3.52 +/- 1.04 mumol/L, respectively). Improvement
of the ESR measurement of oxyradical adducts has been previously obtained by
addition of a new sensitive nitrone (DEPMPO), which acts as a spin-trap. However,
in our experiment the ESR signal-to-noise ratio was too low to detect
significative oxyradicals adducts in total venous blood of NIDDM patients having
a weak production of ROS. A significant difference (p < 0.002) was observed in
DMSO/AFR index between controls (24.00 +/- 4.10 nmol/L) and NIDDM patients (7.28
+/- 2.36 nmol/L) suggesting ascorbate depletion related to the free radical
production. CONCLUSION: The DMSO/AFR index could be an interesting additional
marker of oxidative stress during a chronic production of ROS.
PMID- 9646945
TI - Interference of 6 beta-hydroxycortisol in the quantitation of urinary free
cortisol by immunoassay and its elimination by solid phase extraction.
AB - OBJECTIVE: To study the cross-reactivity of 6 beta-hydroxycortisol (6 beta-OHF)
with anticortisol antibodies and subsequent interference with urinary free
cortisol (UFC) quantitation in commercial immunoassay kits. A solid-phase
extraction (SPE) technique was evaluated for removal of 6 beta-OHF from the
specimen. METHODS: Interference by 6 beta-OHF was studied in three enzyme
immunoassay and three radioimmunoassay kits. Interference was assessed by the
multiple regression equation derived from a 4 x 4 matrix composed of four levels
of cortisol and four levels of 6 beta-OHF. Sep-Pak Plus C18 cartridges were used
to remove 6 beta-OHF from the specimens, and optimum conditions for fractionating
6 beta-OHF from cortisol were determined by eluting the cartridge with a stepwise
increment in methanol concentration. HPLC was used to monitor cortisol and 6 beta
OHF in the sample and cartridge eluates. RESULTS: Cross-reactivity of 6 beta-OHF
with anticortisol antibodies was variable and depended on the cortisol kit used
with a range from 0.1 to 10%. Multiple regression analysis indicated that 6 beta
OHF interfered positively with the cortisol assay regardless of cortisol
concentrations. Extraction of UFC by methylene chloride as recommended by some
immunoassay kits yielded a significant constant error to the UFC results which
was nearly proportional to the added levels of 6 beta-OHF. SPE of samples
completely removed 6 beta-OHF from the specimen when a 40% methanol elution step
was included. Consequently, specimens processed in this manner did not show
interference in UFC measurements even in samples spiked with 2.38 mumol/L of 6
beta-OHF. CONCLUSIONS: Elevated urinary 6 beta-OHF may be a significant source of
interference in UFC immunoassays. SPE of samples prior to analysis would be a
simple and inexpensive means for removing 6 beta-OHF from urine specimens,
therefore, increasing accuracy and precision in UFC measurements by immunoassay.
PMID- 9646946
TI - Myocardial ischemic injury and purine metabolism in patients undergoing coronary
artery bypass.
AB - OBJECTIVES: High-energy phosphates and their catabolic products were determined
in myocardium during coronary artery bypass surgery with blood cardioplegic
reperfusion in order to evaluate the effects of aortic cross-clamping and
reoxygenation on myocardial purine metabolism. DESIGN AND METHODS: Transmural
left ventricular biopsy specimens were taken with ITu-Cut biopsy needles, before
aortic cross-clamping, before cross-clamp removal and after 30' of reperfusion;
perchloric extracts of the material were analyzed for nucleotide content by
capillary zone electrophoresis (CZE). The CZE procedure used separates the
complete spectrum of purine metabolites in myocardial extracts obtained from 0.6
8.6 mg biopsy material. RESULTS: The basal values of ATP/ADP ratio and energy
charge were low, IMP content was high. After the ischemic period, ATP levels
further decreased and IMP, nucleosides and bases accumulated. After reperfusion,
nucleoside and base basal levels, but not energy charge, were restored to some
extent. CONCLUSIONS: The study arises the problem of myocardial preservation
during heart surgery. In this investigation, capillary electrophoresis was an
extremely adaptable technique for the evaluation of ischemic injury and could be
useful in studying the effects of cardioplegic solutions.
PMID- 9646947
TI - Accelerated linear growth and advanced bone age in Sotos syndrome is not
associated with abnormalities of collagen metabolism.
AB - OBJECTIVES: To investigate whether the advanced bone age in Sotos syndrome is
associated with alterations in type I collagen metabolism in bone. DESIGN AND
METHODS: The metabolism of collagen was studied by analyzing the production, gene
expression and degradation of type I collagen in dermal fibroblast strains from
patients with Sotos syndrome and comparing them with fibroblasts from age-matched
healthy subjects. Collagen production was determined as collagenase digestible
radioactivity and collagen mRNA levels were measured by RT-PCR. Collagen
degradation was assessed by specific collagenase assay and gelatin zymography. To
determine the structural defects in type I collagen, the newly synthesized
proteins were analyzed by SDS-PAGE before and after proteolytic digestion with
pepsin. RESULTS: In the present study, we have demonstrated that the collagen
production, secretion and degradation in Sotos syndrome is comparable to
controls. In addition, no qualitative differences in mRNA transcripts for type I
collagen were detected between the control and Sotos syndrome fibroblasts. The
secretion and intracellular accumulation of procollagen is also comparable to
controls. The analysis of both procollagen and collagen on SDS-PAGE did not
exhibit any major structural changes as compared with controls. CONCLUSIONS: Our
results on several aspects of collagen metabolism have demonstrated for the first
time that collagen, the most abundant of mammalian proteins and the major
constituent of bone, is normal in patients with Sotos syndrome. Therefore, it
appears that the advanced bone age and accelerated linear growth seen in patients
with Sotos syndrome may not be attributed to inherent abnormalities of collagen
metabolism. The etiology and the pathogenesis of Sotos syndrome still remains
unclear.
PMID- 9646948
TI - A prospective longitudinal study of platelet angiotensin II receptors for the
prediction of preeclampsia.
AB - OBJECTIVES: We developed a simplified method using a relatively small volume of
blood for the determination of platelet angiotensin II receptors by saturation
analysis and we evaluated its performance for the prediction of preeclampsia.
DESIGN AND METHODS: A platelet suspension with minimal contamination by
leukocytes and erythrocytes is obtained by centrifugation and washing. The
platelet concentrate is incubated in a multi-well plate with increasing
concentration of radiolabelled angiotensin II in the presence or absence of an
excess of unlabelled angiotensin II. Bound and free fractions are separated using
an oil mixture. Maximum binding is determined by Scatchard plot. This method was
compared with a previously reported method. Our method was prospectively
evaluated in 801 women attending our institution for routine prenatal care. A
specimen was obtained at each trimester of pregnancy whenever possible. Diagnosis
of preeclampsia was done postnatally by an experienced obstetrician. RESULTS: The
method showed acceptable correlation with a previously published method although
a proportional bias of 2.1 was observed between the two methods. No differences
in mean maximum binding were observed between normal and affected pregnancies at
either trimester. Even when the results were analyzed longitudinally, using the
change in maximum binding between two trimesters for each patient, no significant
increase could be documented in preeclamptic pregnancies. CONCLUSIONS: Platelet
angiotensin II receptor measurement is not a clinically useful marker for the
prediction of preeclampsia.
PMID- 9646949
TI - Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL
oxidation.
AB - OBJECTIVES: To additionally test validity of the recently developed method (LDL
baseline diene conjugation, LDL-BDC) for determination of circulating oxidized
LDL. DESIGN AND METHODS: A detailed comparison between the ultracentrifugation
and heparin precipitation methods for LDL isolation was performed to test
suitability of the fast precipitation method. Validity of LDL-BDC as an indicator
of circulating oxidized LDL was tested by comparing LDL-BDC to results obtained
by the immunological autoantibody method. RESULTS: BDC values in LDL isolated by
heparin precipitation did not differ from those isolated by sequential
ultracentrifugation. While highest amount of diene conjugation was found in LDL
(40% of that in serum), substantial amounts were also found in VLDL (31%) and HDL
(25%). When analyzed in the same samples, assays for the titer of autoantibodies
against oxidized LDL and LDL-BDC were found to show good correlation (r = 0.57, p
= 0.001, n = 29). CONCLUSIONS: These results, together with thus far conducted
studies on clinical applicability of the method, indicate that LDL-BDC is a
promising candidate in search for a method for estimation of LDL oxidation in
vivo.
PMID- 9646950
TI - A survey to identify potential outcome indicators for a hospital blood glucose
monitoring program.
AB - OBJECTIVE: A survey of operators of a bedside blood glucose monitoring (BGM)
program at a tertiary health care institution was performed to identify potential
outcome indicators for our quality assurance program. DESIGN AND METHODS: 170
surveys were randomly distributed to each nursing unit. The survey consisted of
20 questions on 4 pages. At the time of the survey, the BGM program consisted of
514 operators and 33 blood glucose meters on 17 inpatient nursing units servicing
a total of 445 hospital beds. RESULTS: Seventy-eight percent of surveys were
returned. Seventy-one percent of operators used the glucose meter at least once a
week, 17% used it less than once a week, and 12% used it less than once a month.
When asked how often they thought operators should perform BGM to ensure
reliability, 65% stated "at least monthly," 8% said "bimonthly," and 27% said "3
to 4 times a year." In the previous 3 months, 59% of operators recalled "never
having to repeat a BGM measurement with the glucose meter." 56% recalled "never
having to confirm a BGM result by sending a venous sample to the central
laboratory," 38% recalled "sending a venous sample once or twice;" 4% recalled
"three or four times;" and 2% recalled "more than four times." Fifty-two percent
recalled having to perform a stat analysis "less than once per month," 37%
recalled "once or twice per month," and 11% recalled "once or twice per week."
CONCLUSIONS: Through this survey we obtained information from our operators about
the current functioning of our BGM program. Based on this information, we were
able to develop a list of potential outcome indicators that we encourage health
care institutions with BGM programs to consider incorporating in their quality
assurance (QA) program.
PMID- 9646951
TI - 5'-nucleotidase activity in lymphocytes from patients affected by B-cell chronic
lymphocytic leukemia.
AB - OBJECTIVES: The activity of membrane-bound ecto-5'-nucleotidase and soluble e-Ns
and c-N-II 5'-nucleotidases was evaluated on lymphocytes from patients affected
by B-cell chronic lymphocytic leukemia (B-CLL). A statistically significative
decrease in ecto-5'-nucleotidase, e-Ns, and c-N-II activities was observed in
peripheral blood lymphocytes and in B and T populations from affected
individuals. DESIGN AND METHODS: For the assay of ecto-5'-nucleotidase, e-Ns, and
c-N-II activity we used a radioactive procedure coupled to HPLC. Since the ecto
5'-nucleotidase is identified as CD73 antigen, we performed immunofluorescence
analysis using a specific monoclonal antibody. We analyzed ecto-5'-nucleotidase
mRNA by RT-PCR to ascertain the possibility of an alteration in the transcription
of its gene. RESULTS: A decrease in ecto-5'-nucleotidase activity was correlated
to reduction in ecto-5'-nucleotidase positive cells (CD73+) in leukemia patients.
RT-PCR produced a fragment of the expected size and the specific mRNA was found
expressed in both healthy subjects and leukemia patients. CONCLUSIONS: The
decrease in ecto-5'-nucleotidase activity in patients with B-CLL is not due to
loss of transcription of the specific mRNA. The presence of point mutations,
splicing alteration, or posttranslational modifications must be investigated. If
a defect at DNA or RNA level will be detected, the molecular analysis will be
considered for diagnosis of B-cell chronic lymphocytic leukemia.
PMID- 9646952
TI - Stability of digoxin and digitoxin in specimens collected in blood collection
tubes containing serum separator gels.
PMID- 9646953
TI - Lipoperoxides kit evaluated for measuring lipoperoxides in biological samples:
reference intervals for human plasma.
PMID- 9646954
TI - Lack of association between apolipoprotein H polymorphism and plasma lipid levels
in Koreans.
PMID- 9646955
TI - Prostate specific antigen production by breast tumors after induction with oral
contraceptives.
PMID- 9646956
TI - Observational studies.
AB - Observational studies are important methodologies to evaluate exposures and risk
factors that are not amenable to experimental trials. They offer the advantage of
being more generalizable to our patients, as these studies may have more liberal
inclusion criteria than the typical randomized trial. Their disadvantage is their
susceptibility to biases and their inability to control for unknown factors that
may impact on the outcome of interest. Establishing causality of an association
noted in observational studies is an intricate process that requires careful
assessment. Clinicians and researchers should be familiar with observational
studies so they may better evaluate a proposed causal relationship and the
quality of reports claiming such relationships. Only then can they determine if
the findings are valid and applicable to their patient population.
PMID- 9646957
TI - Randomized controlled trials.
PMID- 9646958
TI - Power and sample size.
PMID- 9646959
TI - Screening and diagnostic testing.
PMID- 9646960
TI - Meta-analysis for the practicing obstetrician-gynecologist.
PMID- 9646961
TI - Decision analysis.
PMID- 9646962
TI - Cost analysis in obstetrics and gynecology.
PMID- 9646963
TI - Interpretation of the literature.
AB - To remain clinically competent, you must read! Continued clinical effectiveness
is learning how to decide when your current diagnostic and management maneuvers
are no longer good enough and need to be changed! The evidence for obstetric and
gynecologic practice is growing exponentially (it is about time!) and it is time
that we, the clinicians, offer our patients the benefits of incorporating that
evidence into practice. Interpretation of the literature is one step along the
way to the evaluation and practice of evidence-based medicine!
PMID- 9646964
TI - The Cochrane Collaboration: evaluation of health care and services using
systematic reviews of the results of randomized controlled trials.
PMID- 9646965
TI - The U.S. Preventive Services Task Force: putting evidence-based medicine to work.
AB - The U.S. Preventive Services Task Force is a prominent example of evidence-based
medicine put to work. The Guide to Clinical Preventive Services and its Canadian
counterpart distill thousands of articles into easily understood guidelines for
the busy clinician. Rather than dictating practice, it provides the scientific
base for prevention services. The second fundamental part of evidence-based
medicine is the filtering of that evidence through the clinical skill of the
clinician. Only the clinician can judge the applicability of the evidence and the
preferences of the woman and her family. Some common preventive practices in
women's health lack a scientific basis. Others clearly work. To maximize benefit,
clinicians should emphasize and encourage prevention strategies that are
effective. These include cervical cytology screening, blood pressure screening,
urine cultures in early pregnancy, testing for phenylketonuria, and discouraging
smoking. No health program can be reviewed in a vacuum. This is especially true
in the managed care era. Clinicians must ask what benefit would have accrued had
the same amount of time and money been spent on alternative programs. If
practices with only a class C recommendation draw money and resources from other
programs of proven worth (e.g., class A recommendations), then the former have a
net negative impact on women's health. The Task Force report helps women,
clinicians, payers, and policymakers make these important decisions.
PMID- 9646966
TI - Practice guidelines--a continuing debate.
PMID- 9646967
TI - Evidence-based healthcare quality management in obstetrics and gynecology.
PMID- 9646968
TI - Intrapartum electronic fetal monitoring: data for clinical decisions.
PMID- 9646969
TI - Vaginal birth after cesarean.
AB - Vaginal birth or trial of labor after previous cesarean delivery represents one
of the most significant changes in obstetric practice. There are numerous reasons
that influence the decision to proceed with either a trial of labor after
previous cesarean delivery or elective repeat cesarean delivery. For the majority
of women with a previous cesarean delivery, a trial of labor should be
encouraged. There are few absolute contraindications. Women with a previous
classical uterine incision should not undergo a trial of labor and should be
delivered once fetal lung maturity is documented. An attempted trial of labor
should not be discouraged in women with a previous low vertical uterine incision,
although the patient should be counseled that the evidence as to the risks and
benefits of a trial of labor is limited. In those situations where the previous
uterine incision is unknown, but suggestive of a classical uterine incision, an
argument can be made for elective repeat cesarean delivery once fetal lung
maturity is documented. When the history of a uterine incision is unknown and
unlikely to be classical, a trial of labor can be attempted after counseling.
Close intrapartum management is warranted in this situation. The optimal
management of labor in women with a previous low transverse uterine incision who
desire a trial of labor with a breech presentation, multiple gestation, orin whom
induction of labor is necessary is uncertain; the evidence as to the risks and
benefits of a trial of labor is limited and obstetric management should be
individualized after counseling. Uterine rupture represents the most catastrophic
complication of a trial of labor after previous cesarean delivery. In women
suspected of having a uterine scar injury, prompt intervention is necessary to
minimize both maternal and neonatal complications. Women who are not successful
with a trial of labor require repeat cesarean delivery and appear to be at
greatest risk for maternal complications. Identifying those women most likely to
be successful with an attempted trial of labor after previous cesarean while also
incurring the least maternal and perinatal morbidity and mortality would be
ideal. At present, however, there is no sufficiently predictive method to
identify those women most likely to benefit from an elective repeat cesarean
delivery. The management of labor in women with a previous uterine scar is not
low risk. As the number of women who attempt vaginal birth after previous
cesarean delivery increases, we should focus on trying to develop reliable
methods of identifying women who should and should not undertake a trial of labor
after cesarean delivery.
PMID- 9646970
TI - Medical management of ectopic pregnancy.
AB - In selected patients who are hemodynamically stable with an unruptured tubal
pregnancy, systemic methotrexate has success rates comparable to laparoscopic
salpingostomy. Larger randomized studies are necessary to adequately assess
subsequent fertility. Local injection of methotrexate or other agents requires a
sonographically visible ectopic as well as technical skills, and has less
consistent success rates than that of systemic MTX therapy.
PMID- 9646971
TI - Treatment of endometriosis.
PMID- 9646972
TI - Prophylactic cesarean for prenatally diagnosed malformations.
PMID- 9646973
TI - Premenstrual syndrome therapy.
PMID- 9646974
TI - Evidence-based management of chronic pelvic pain.
AB - Diagnosis and management of chronic pelvic pain are greatly facilitated by a
multidisciplinary approach integrating medical intervention with identification
and management of socioenvironmental problems, cognitive-behavioral pain
strategies, and treatment of concurrent psychological morbidity. Available
evidence suggests that outcomes, including pain severity, general health and
functional status, and disability are more significantly improved after this
approach than after isolated medical or surgical interventions. Because of the
chronic nature of many of the underlying psychological and social factors
predisposing to chronic symptom formation and maintenance, care of the patient
with chronic pelvic pain must be continuous and longitudinal if recurrent adverse
sequelae, including disability, inappropriate healthcare utilization, and
recurrent depression, are to be prevented.
PMID- 9646975
TI - Management of idiopathic thrombocytopenic purpura in pregnancy.
PMID- 9646976
TI - Epidural analgesia for labor: effect on the cesarean birth rate.
PMID- 9646977
TI - Antibiotic therapy for preterm premature rupture of membranes.
AB - Antibiotic treatment of the patient with preterm premature rupture of membranes
remote from term significantly prolongs pregnancy and reduces amnionitis without
increasing the risk of cesarean delivery. Antibiotic treatment reduces perinatal
infectious morbidity including neonatal sepsis, GBS sepsis, and pneumonia.
Stratified analysis of the currently available prospective trials also
demonstrates a significant reduction in gestational-dependent morbidity,
specifically respiratory distress and intraventricular hemorrhage with treatment.
This is supported by a reduction in composite infant morbidity and other
gestational age-dependent morbidities in the NICHD-MFMU trial. Although the
optimal treatment regimen has not been determined, limited duration broad
spectrum antibiotic treatment is justified in the setting of conservative
management of pPROM remote from term. The patient with pPROM and documented
pulmonary maturity near term may benefit more from expeditious delivery than from
expectant management with antibiotics.
PMID- 9646978
TI - Anatomy of the pleura.
AB - The lung and heart, the vital organs, have to be protected and also have to move
and change volume continuously to function. For the best protection and function
of the lung, the thorax is shaped almost like a bellows with the diaphragm as the
moving part. Furthermore, the outer surface of the lung and the inner surface of
the protective thoracic cage are covered by an elastic, serous, and lubricating
membrane to form the pleural cavity. This is almost like inserting a sealed-wet
and stretchable-plastic bag between the lung and the thoracic wall and diaphragm
to decrease friction. The lubrication is accomplished by the facing mesothelial
cells that have bushy-surface microvilli enmeshing hyaluronic acid-rich
glycoproteins. The amount of fluid in the pleural cavity is regulated by the
hydrostatic-osmotic pressure relationship and pleuro-lymphatic drainage. Excess
fluid, large particles, and cells in the pleural cavity are removed through
preformed stomas assisted by respiratory movements. The stoma is found only in
the anterior lower thoracic wall and diaphragm and is like the drain of a sink.
Finally, clinical and subclinical injuries of the pleura appear to occur often.
Reactive mesothelial cells constantly repair the damages and keep the pleural
cavity open. Without mesothelial cells, the lung cannot function properly and the
pleural cavity will be quickly obliterated by fibrosis.
PMID- 9646979
TI - Mechanical coupling and liquid exchanges in the pleural space.
AB - The pleural space provides the mechanical coupling between lung and chest wall:
two views about this coupling are reported and discussed. Information on volume,
composition, thickness, and pressure of the pleural liquid under physiologic
conditions in a few species is provided. The Starling pressures of the parietal
pleura filtering liquid into pleural space, and those of the visceral pleura
absorbing liquid from the space are considered along with the permeability of the
mesothelium. Information on the lymphatic drainage through the parietal pleura
and on the solute-coupled liquid absorption from the pleural space under
physiologic conditions and with various kinds of hydrothorax are provided.
PMID- 9646980
TI - CT and MR in pleural disease.
AB - A number of different imaging modalities can be used in the assessment of pleural
disease. Although ultrasound has been the more traditional method, CT has found
increasing utility for the assessment of the empyema and loculated pleural fluid
collections prior to drainage and the evaluation of benign and malignant pleural
tumors. MRI has a limited but important role particularly in the evaluation of
focal pleural tumors such as lipomas and in determining the extent of malignant
mesothelioma prior to therapy.
PMID- 9646981
TI - Evaluating diagnostic tests in the pleural space. Differentiating transudates
from exudates as a model.
AB - Physicians have a staggering variety of diagnostic tests available for directing
their diagnostic and therapeutic decisions. Technologic advances in laboratory
science have increased the sophistication of new tests and accelerated their rate
of adoption into clinical practice. Unfortunately, studies that report the value
of new diagnostic tests often fail to follow accepted methodologic standards for
unbiased test assessment or provide clinicians with sufficient information for
the intelligent evaluation of a test's performance and applicability. The
following review of pleural fluid tests that discriminate between exudative and
transudative effusions serves to highlight important methodologic considerations
in the assessment of diagnostic tests.
PMID- 9646982
TI - Diagnostic thoracoscopy.
AB - Thoracoscopy provides diagnosis of pleural diseases with a high degree of
accuracy. Moreover, this procedure allows a careful pleural staging of the
disease, in particular for pleural cancer, which is important for the prognosis
and therapeutic decision. This article focuses on the technique, indications, and
results of medical thoracoscopy.
PMID- 9646983
TI - Asbestos-induced pleural disease.
AB - Asbestos-induced pleural disease has become the most common manifestation of
asbestos exposure. Asbestos has an unusual affinity for the pleural space and
leads to plaques, benign effusions, fibrosis, and malignant mesothelioma. The
explanation for its affinity for the pleura may lie in part with new evidence
showing that asbestos fibers can accumulate in certain regions of the parietal
pleura at higher concentrations than in the lung. With the control of industrial
exposures to asbestos, the incidence of this disease should decrease, with the
incidence of mesothelioma peaking in the years 2000 to 2020. Nonetheless, the
toxic features of asbestos including shape, chemical composition, and surface
characteristics should be understood to avoid toxicity in fibers used to replace
asbestos and to know the risks of low level exposures from asbestos currently in
our environment.
PMID- 9646984
TI - Drug-induced pleural disease.
AB - Drug-induced pleural disease in the form of pleural fibrosis or pleural effusions
is a common but frequently overlooked toxic or allergic manifestation of usage of
a particular class of drugs. A detailed history of drug intake will often unveil
the cause for the pleural pathology. Discontinuation of the drug with or without
the addition of steroid therapy may be helpful.
PMID- 9646985
TI - Pleural disease in patients with acquired immune deficiency syndrome.
AB - Given the multiple impairments in host defense that occur during HIV infection,
patients with AIDS are at risk for a variety of pleural infections and neoplasms.
Of infectious causes, bacterial parapneumonic effusions and empyemas and
tuberculous pleurisy occur more frequently than effusions caused by P. carinii.
In each case, therapy is directed at eradication of the causative organisms. In
the setting of systemic Kaposi's sarcoma, pleural involvement is common, although
diagnosis is difficult and therapeutic options are limited. Pleural effusions
caused by non-Hodgkin's lymphoma often occur in the setting of pulmonary
parenchymal disease and can be diagnosed cytologically. The recently described
entity of primary effusion lymphoma occurs in the absence of solid-organ
involvement. The development of a spontaneous pneumothorax in a HIV-infected
individual should prompt a search for P. carinii infection. Although these
pneumothoraces often recur and are difficult to manage, recent series suggest
that surgical approaches to bronchopleural fistulas are reasonable in selected
patients.
PMID- 9646986
TI - Malignancy metastatic to the pleura.
AB - Malignancy is one of the most common causes of exudative effusions and increases
in incidence in the elderly. Lung cancer is the most common cause of malignant
effusion caused by contiguous spread and its propensity to invade the pulmonary
vasculature and embolize to the visceral pleura. Lung, breast, ovary, and gastric
cancer and lymphomas account for about 80% of all malignant effusions. Dyspnea
and cough are the most common symptoms at presentation. Thirty percent of
patients have a low pleural fluid pH (> or = 7.30) and glucose (> 60 mg/dL) at
presentation, which predicts a decreased survival, an increase yield on
diagnostic studies, and a poor response to chemical pleurodesis. Talc by poudrage
or slurry is the most successful pleurodesis agent. Pleural peritoneal shunt is
an option for patients with an intractable, symptomatic malignant effusion who
cannot undergo or who have failed pleurodesis.
PMID- 9646987
TI - Common pleural effusions in children.
AB - The evaluation of pleural effusions in children differ from that of the adult in
cause, symptom presentation, character of the fluid, techniques for diagnosis,
treatment or management, and prognosis. These similarities and differences are
reviewed with emphasis on the treatment of empyema.
PMID- 9646988
TI - Management of parapneumonic effusions.
AB - When a patient with a parapneumonic pleural effusion is first evaluated, a
therapeutic thoracentesis should be performed if more than a minimal amount of
pleural fluid is present. Fluid obtained at the therapeutic thoracentesis should
be gram-stained and cultured and analyzed for glucose, pH, LDH, white blood
cells, and differential cell count. If the fluid cannot be drained because of
loculations, a chest tube should be inserted and thrombolytic agents
administered. If the pleural fluid recurs after the initial therapeutic
thoracentesis but the patient is doing well clinically and the initial pleural
fluid glucose was greater than 60 mg/dL; the pH, greater than 7.2; the LDH, less
than three times the upper normal limit for serum and the cultures are negative;
he or she can be observed. If one or more of the aforementioned criteria are not
met, a second therapeutic thoracentesis should be performed, with repeat
diagnostic evaluations of the pleural fluid. If the fluid recurs a second time, a
small chest tube should be placed if the pleural fluid glucose and pH were lower
and the LDH higher on the second thoracentesis than on the first thoracentesis.
Patients with loculated-parapneumonic effusions should be treated with tube
thoracostomy and thrombolytic agents. If drainage is incomplete, thoracoscopy,
with breakdown of adhesions and debridement of the pleural space, is indicated.
If thoracoscopy is unsuccessful, then thoracotomy, with decortication, is
indicated unless the patient is too debilitated.
PMID- 9646989
TI - Therapeutic thoracoscopy.
AB - Thoracoscopy provides a minimally invasive window to the pleural space, lung, and
mediastinum. Further advances prompted by improvements of specifically designed
endoscopic instruments and procedural techniques are expected. There is no doubt
that thoracoscopy has a place among therapeutic procedures in the chest. The time
proven principles of thoracic surgical intervention, particularly in regard to
patients with cancer, however, must not be neglected. A beckoning window always
offers new opportunities, but the open door of classic surgical techniques should
not be ignored.
PMID- 9646990
TI - Surgical management of empyema.
AB - The cause and presentation of empyema thoraces has changed little since it was
first described. The natural history of the disease can be divided into different
stages. Different therapeutic measures, medical and surgical, are available for
the treatment at various stages. The management of empyema is discussed,
emphasizing the surgical aspects.
PMID- 9646991
TI - Management of undiagnosed persistent pleural effusions.
AB - Difficult to diagnose pleural effusions are not uncommonly encountered in
clinical practice. We define these effusions as those that remain undiagnosed
after initial thoracentesis and repeat thoracentesis with pleural biopsy.
Tuberculosis and malignancy are often found to be the underlying causes when a
diagnosis is ultimately made, but other causes, including pulmonary embolism and
intra-abdominal conditions, need to be considered as potential causes of the
difficult to diagnose effusions. In selected cases, presumptive treatment of
tuberculosis is indicated whereas in others, a decision must be made either to
obtain a definitive diagnosis by invasive surgical procedures or to follow the
patient with careful observation and watchful waiting.
PMID- 9646992
TI - The history of policy and practice related to the perinatal hospital stay.
AB - The issue of early newborn discharge has received widespread attention in both
the lay press and the medical literature over the past few years, culminating in
passage of Public Law 104-204, Title VI: The Newborns' and Mothers' Health
Protection Act of 1996. This article reviews the road to passage of this
legislation, including the historical trends and forces determining postpartum
length of stay in the United States, the evolution of guidelines as put forth by
official representative bodies such as the AAP, the current status of state and
federal legislation, and the relationship between length of stay and follow-up
practices. The status of newborn length of stay in other countries also is
discussed.
PMID- 9646993
TI - The transition to extrauterine life and disorders of transition.
AB - With shorter postnatal hospital stays, concern has arisen that many infants may
be discharged prior to completion of the transition to extrauterine life, a time
of dynamic physiologic change when many neonatal problems may present. This
article reviews the physiology of the neonatal transition together with common
transitional disorders. Most disorders of transition present at typical postnatal
time periods, permitting their timely anticipation and treatment. Moreover, many
are associated with factors that may further aid the clinician in defining those
infants at highest risk.
PMID- 9646994
TI - Jaundice in full-term and near-term babies who leave the hospital within 36
hours. The pediatrician's nemesis.
AB - There has been an increase in hyperbilirubinemia in the newborn population and,
perhaps, an increase in bilirubin encephalopathy. The early discharge of newborns
from hospital has made it necessary for us to reorient our thinking about
bilirubin levels in the first 24 to 48 hours of life and alter our approach to
follow-up. The pediatrician must evaluate and follow infants who have risk
factors for the development of severe hyperbilirubinemia, paying particular
attention to the breast-feeding, near-term infant.
PMID- 9646995
TI - The optimization of breast-feeding in the perinatal period.
AB - Mounting scientific evidence documents the diverse health benefits of successful
breast-feeding for infants and mothers. The trend toward earlier discharge of
newborns, however, has been linked with adverse outcomes in breast-fed babies,
including hypernatremic dehydration and hyperbilirubinemia. This article reviews
practical strategies for promoting the successful initiation of breast-feeding,
beginning with effective prenatal education and a screening breast exam to detect
lactation risk factors. Supportive hospital practices are discussed, including
the Baby-Friendly Hospital Initiative and correct breast-feeding technique. The
importance of regular, effective removal of milk for continued milk production is
explained. The early follow-up of infants after hospital discharge and the use of
specific maternal and infant criteria to assess the onset of breast-feeding can
readily identify mother-baby pairs who require timely intervention to improve
breast-feeding outcome.
PMID- 9646996
TI - The newborn at risk for serious infections.
AB - Early discharge of suitable newborns is rapidly becoming a hospital standard. One
concern is that truncated hospital observation of the infant during the first
days of life, even with home visits or early clinical appointments, would allow
early signs of a serious infection to go unnoticed, which could lead to a missed
chance for early therapy and could imperil the child's favorable recovery. An
analysis of available data for early onset neonatal bacterial sepsis and neonatal
herpes virus infection shows that this new practice should not unduly place
newborns at risk of treatable infections, however, so long as conventional risk
factors are appreciated and reasonable, nationally sanctioned discharge criteria
are followed.
PMID- 9646997
TI - The drug-exposed infant in the well-baby nursery.
AB - Maternal substance use can have medical and developmental consequences for the
newborn. Many drug-exposed infants are admitted to term nurseries, and the
newborn clinician who often has never previously met the mother must gather both
objective and subjective information about problems in the pregnancy and delivery
that may indicate maternal substance abuse. This article addresses the prevalence
of maternal substance abuse in the United States, the long-term consequences of
in utero drug exposure that makes early identification important, the
identification of a drug-exposed neonate, and in-hospital care and discharge
management of the drug-exposed newborn.
PMID- 9646998
TI - Congenital malformations presenting during the neonatal period.
AB - Discharge of the newborn within 24 to 48 hours after birth makes it more
difficult to detect some congenital malformations and increases the need for
careful examination and review of the history of the pregnancy, delivery, and
nursery course. Progressive physiologic changes after birth, especially in the
cardiovascular system, precede the development of signs indicative of disease for
certain congenital malformations. Discharge before these changes occur may delay
their detection because the newborn is not being monitored by medical or nursing
caregivers. The AAP Committee on the Fetus and Newborn has published guidelines
for criteria for safe discharge and follow-up evaluation to help create a safe
situation for such early discharges. Some specific observations at birth may lead
to earlier diagnosis. Careful attention to subtle differences between the initial
and follow-up examination, such as a changing cardiac murmur or quality of pulses
or abdominal fullness, may provide clues to the diagnosis of congenital
malformations. Coordinated suck and swallow with successful feeding and passage
of stool and urine within 24 hours after birth should occur before discharge.
Reports of feeding difficulties should be reviewed. Although a thorough
examination is facilitated by a sleeping infant, documentation of a normal
pitched cry helps in the evaluation of the upper airway. Parents should be
counseled about signs of illness that warrant medical attention, and early follow
up is needed to detect problems early enough to intervene effectively. In
addition, although passage of a feeding tube through each nare and to the stomach
with aspiration and measurement of gastric volume is not a routine procedure in
the well, term newborn, this may be a useful early diagnostic tool in infants
with signs or a maternal or nursery history suggestive of nasal or GI
obstruction.
PMID- 9646999
TI - Metabolic screening.
AB - Mandated, universal metabolic screening has been an effective tool for the early
identification of infants with metabolic disorders, particularly those amenable
to improved outcome with dietary management or medication. Although the
availability of diagnosis long before symptoms occur may be useful to preclude
expensive diagnostic evaluation when the subtle early symptoms begin and may
allow for genetic counseling and testing in affected families, many concerns have
been raised regarding the psychologic impact of presymptomatic diagnosis of
diseases that are either fatal or for which no effective treatment is available.
Before mass screening is initiated, careful pilot studies need to be done to
evaluate sensitivity and specificity as well as the impact of early
identification on infant outcome.
PMID- 9647000
TI - Maternal education during the perinatal period.
AB - The nature of perinatal education has been transformed, reflecting the changes in
health care and health care consumers. Because of short maternity stays, the
venue of most perinatal education, especially postpartum education, has moved
from hospitals to other areas, including the home. In light of conflicting
findings of past research examining the effectiveness of prenatal education as
well as gaps in the literature, there is a need for research on the content,
methods, providers, and dose effect of perinatal education.
PMID- 9647001
TI - Medical conditions of the puerperium.
AB - The puerperium is a time of continued, dramatic pregnancy-associated adaptation.
Although much less common than in the early part of the century, maternal death
can still occur from common postpartum problems such as infection, hemorrhage,
and disease. This article reviews the physiologic and emotional changes as well
as the clinical management of common problems in the puerperium.
PMID- 9647002
TI - The perinatal assessment of psychosocial risk.
AB - Although evaluation of psychosocial risk factors prior to perinatal hospital
discharge has been advocated, the means for accomplishing such an evaluation are
not well established. This article reviews several major psychosocial risk
factors together with instruments that have been utilized to assess them during
the perinatal period. Formal constructs reviewed include anxiety, depression,
self-concept, general attitudes, life events, stress, adaptation, social support,
marital and family functioning, and the home environment. Ongoing assessment of
psychosocial status using formal instruments during routine perinatal care may
provide a more complete picture of the psychosocial needs of the individual
mother and her family, allowing for more appropriate, timely intervention and
utilization of social and health care resources.
PMID- 9647003
TI - Perinatal screening for child abuse and neglect.
AB - An increased awareness of the frequency and severity of child abuse and neglect
in our society has prompted consideration of the feasibility of perinatal
screening and early intervention for this problem. This article reviews the
available information on screening and early intervention for high-risk parenting
in the perinatal period. The advantages, disadvantages, and cost-effectiveness of
screening and intervention for children and families at risk for abuse and
neglect are also discussed.
PMID- 9647004
TI - Assessing parent-infant interaction during the perinatal period. Some cautions.
AB - Pediatricians have recently been urged by professional groups to pay increased
attention to parental behavior when serving and discharging newborns. These
exhortations are well intended, but they may reflect a misunderstanding of
developmental processes and foster a mistaken belief in the ease with which
parenting problems can be identified and remedied. This article describes how
early experiences affect children's development and then contrasts this view with
a popular perspective based on misapplication of the medical model to the
conceptualization of behavioral development.
PMID- 9647005
TI - Follow-up of newborns and their mothers after early hospital discharge.
AB - As postpartum hospital stays have become increasingly shorter, more attention has
been focused on the importance of routine postdischarge follow-up for newborns
and mothers. Recent guidelines and legislation, however, include few specifics on
how follow-up services should be provided. Based on the authors' review of the
recent literature, it was concluded that the research to date provides little
useful information to guide follow-up practices under current conditions.
Additional studies that focus on postdischarge follow-up, rather than on length
of hospital stay, are needed to provide the basis for more specific practice
guidelines.
PMID- 9647006
TI - Economic aspects of the perinatal hospital stay.
AB - This article concentrates on the economics of the perinatal hospital stay for
normal vaginal and cesarean section deliveries. Published studies in the United
States are reviewed under three headings: inpatient costs for traditional stays,
outpatient costs for postpartum services, and costs for short stays with follow
up services. Despite the increasing attention on length of stay after delivery,
there has been minimal research examining the true costs of an early discharge
program and services compared with longer hospital stays. Formal analysis of
alternative strategies and well-designed clinical studies are needed before an
optimal policy for caring for mothers and infants can be identified.
PMID- 9647007
TI - Early discharge of premature infants. A critical analysis.
AB - Although significant advances in the medical management of acutely ill preterm
infants have resulted in unprecedented rates of survival, issues surrounding the
convalescent care, discharge preparation, and readiness of parents or other
caregivers have been less well studied and represent the art of medicine. Recent
consensus statements provide a degree of content validity; however, important
areas of scientific inquiry remain. Much is left to understand about the
pathophysiology, management, and outcomes of apnea, bradycardia, and oxygen
desaturation episodes continuing at term. Why do the most immature infants have a
delay in the maturation of respiratory control? Do breathing studies really
provide information that predicts subsequent respiratory control abnormalities?
If methylxanthines are used at discharge, what criteria should be adhered to
regarding their discontinuation? How is nutrition best provided while
transitioning to home? In infants whose mothers desire exclusive breast-feeding,
should gavage feeds be used to supplement in order to avoid bottle-feedings? How
long should breast milk be fortified, and when should supplemented artificial
milks be used and for what period of time postdischarge should these more
expensive special-discharge artificial milks be used? What other supplements,
such as inositol, vitamins, or antioxidants, should be provided in order to
achieve optimal growth and development? Technology-dependent infants pose even
greater complexities. Some infants and families adapt to extensive use of
technology in the home. In other situations, basic infant care is difficult to
achieve. What are the essential components for successful early discharge, and
how can the studies involving selected families be made universal? How can NICUs
better prepare fathers and mothers for premature parenthood? To what extent are
we overwhelming families with additional responsibilities and expectations that
may compromise their competency in basic parenting? Furthermore, the degree of
provider variation in evaluating and providing for discharge planning is now
being more carefully studied. In some circumstances, integrated teams in the NICU
have facilitated the discharge process saving days of hospitalization, whereas in
others adherence to discharge planning guidelines has lengthened the stay in the
NICU and resulted in higher costs. What is the ideal system for achieving
coordination of care without co-opting parental choices in assuming more care
responsibility than is comfortable? In the design of tertiary care facilities,
more attention to space for rooming-in experiences needs to receive greater
priority. Furthermore, because of intensity of care, adverse environmental
stimuli, and for issues of better resource utilization, should not most
previously ill infants be discharged from level II or intermediate care centers?
Finally, issues of increasing decision-making responsibility placed on parents
(with the reassurance and guiding hand of dedicated physicians and nurses focused
on individual infants) must never be made subservient to the economic whims of
insurers to decrease costs without understanding the value of the entirety of the
care process for critical illness, through convalescence, to it is hoped a
supportive and nurturing environment in the home. Our patients deserve no less.
The questions posed present a sample of issues yet to be scientifically
addressed. These and many other questions need to be answered before we fully
understand the optimal process of discharge for the preterm infant.
PMID- 9647008
TI - Successful antiviral therapy and prognosis in cirrhosis due to hepatitis B.
PMID- 9647009
TI - Teaching irritable bowel syndrome patients to care for themselves.
PMID- 9647010
TI - The origin of 20th century discoveries transforming clinical gastroenterology.
PMID- 9647011
TI - Performing a cost-effectiveness analysis: surveillance of patients with
ulcerative colitis.
AB - OBJECTIVE: To illustrate the principles of cost-effectiveness analysis, this
third article in the "Primer on Economic Analysis for the Gastroenterologist"
applies published criteria for appraising an economic analysis to a study of the
cost-effectiveness of surveillance of patients with ulcerative colitis. METHODS:
We review and apply the 10 standard criteria for critical appraisal and
evaluation of cost-effectiveness analyses. SUMMARY: We outlined the development
and critique of a decision analytic model that examines the cost-effectiveness of
surveillance of patients with ulcerative colitis, and we compared the cost
effectiveness of surveillance of patients with ulcerative colitis to other well
accepted medical practices.
PMID- 9647012
TI - Gastrointestinal manifestations of Chagas' disease.
AB - Chagas' disease is an infectious disease that affects millions of people in Latin
America and is increasingly seen outside endemic areas. A substantial number of
patients develop gastrointestinal disorders secondary to lesions of the enteric
nervous system. The purpose of this article is to review the current knowledge
about gastrointestinal manifestations of Chagas' disease, including disorders
other than the well-known gross dilations of esophagus and colon.
PMID- 9647013
TI - The watermelon stomach: clinical presentation, diagnosis, and treatment.
AB - The watermelon stomach syndrome is an increasingly recognized cause of persistent
acute or occult gastrointestinal bleeding, typically in elderly women. This
disorder often presents with severe iron deficiency anemia, and a variety of
associated conditions including autoimmune disease, cirrhosis, achlorhydria, and
hypochlorhydria. Diagnosis is made by the characteristic endoscopic appearance of
visible linear watermelon-like vascular stripes in the antrum. Histology confirms
the vascular nature of this disorder, showing dilated and thrombosed capillaries
in the lamina propria, associated with reactive fibromuscular hyperplasia. The
optimum treatment of choice is not known. Several treatment options, including
surgical antrectomy, and endoscopic photocoagulation with Nd:Yag laser, heater
probe therapy, and bipolar electrocautery, have yielded excellent results.
Pharmacological agents have also been used to treat selected numbers of patients,
most of which comprise a small number of case reports.
PMID- 9647014
TI - Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to
interferon alpha therapy and disease prognosis. European Concerted Action on
Viral Hepatitis (EUROHEP)
AB - OBJECTIVE: The aim of this study was to evaluate the incidence, prognostic
factors and clinical significance of delayed clearance of serum HBsAg in
compensated cirrhosis B. METHODS: This was a retrospective cohort study of 309
consecutive white patients with biopsy-proved compensated cirrhosis type B.
RESULTS: During a mean follow-up of 68 months, HBsAg loss occurred in 32
patients, including 16 (8%) of 196 untreated patients (mean annual incidence
0.8%), 8 (10%) of 82 interferon (IFN) alpha-treated patients and eight patients
who had been treated with other antivirals or steroids. The 5-yr probability of
HBsAg loss was 4% and 16% for untreated and IFN-treated patients, respectively (p
= 0.0001). Cox's regression analysis identified hepatitis B e antigen-positivity
at entry as the sole independent prognostic factor for HBsAg loss. Of the 32
patients who lost HBsAg, one (3%) subsequently developed hepatocellular carcinoma
(HCC) and died, whereas, among the patients who remained HBsAg-positive, 11%
developed HCC and 20% had died. The probability of HCC appearance was lower (p =
0.0137) and survival was longer (p = 0.0006) in patients who cleared HBsAg
compared with patients with HBsAg persistence. CONCLUSION: The incidence of HBsAg
loss is about 0.8% in cirrhosis type B. Prognostic factors for clearance of HBsAg
are initial HBeAg positivity and therapy with alpha interferon. Patients with
cirrhosis type B, who lose HBsAg, have a low risk for liver cancer or liver
related death.
PMID- 9647015
TI - Effects of an irritable bowel syndrome educational class on health-promoting
behaviors and symptoms.
AB - OBJECTIVE: The degree to which patient education in the areas of diet, exercise,
and stress management can improve symptoms of irritable bowel syndrome (IBS)
through healthier lifestyle behaviors is unknown. The aim of this study was to
determine the effects of outpatient education on the short and long term
outcomes, and the association between health-promoting behaviors and symptoms.
METHODS: Pender's Health Promotion Model provided the theoretical framework. The
study had a prospective longitudinal design. A consecutive sample of 52 adult
outpatients with IBS attended a structured class that taught health-promoting
modifications of lifestyle. Participants completed the Health-Promoting Lifestyle
Profile (HPLP) and selected items from a Bowel Disease Questionnaire (BDQ) before
the class and 1 month and 6 months later. Spearman rank correlations were used to
assess the association between HPLP and symptom scores. Wilcoxon rank sum tests
compared changes in scores versus their baseline values. RESULTS: Response rates
at 1 and 6 months were 75% and 83%, respectively. Results revealed significant 1-
and 6 month-improvements in pain and Manning symptoms (p < 0.01) and in some HPLP
scores (exercise at 1 month, p < 0.05; stress management at 6 months, p < 0.01).
Significant associations were found between some, but not all, HPLP and symptom
scores over time. CONCLUSION: A structured IBS educational class for patients
with IBS improved symptoms and some health-promoting behaviors. However,
relationships among specific behaviors and specific symptoms did not consistently
correspond with this improvement.
PMID- 9647016
TI - Effectiveness and patient satisfaction with nurse-directed treatment of Barrett's
esophagus.
AB - OBJECTIVE: Using clinical practice guidelines, a registered nurse adjusted
antireflux medications, evaluated esophageal biopsy reports, determined the
interval between surveillance endoscopies, and provided education for patients
with Barrett's esophagus. No previous reports have assessed the effectiveness or
patient satisfaction associated with registered nurse-provided primary care.
Because estimates of the incidence of dysplasia and adenocarcinoma vary widely,
we also prospectively followed a cohort of patients with Barrett's esophagus.
METHODS: Charts were reviewed to determine the frequency of variation from
guidelines, the annual incidence of dysplasia and adenocarcinoma, and frequency
of reflux symptoms. Patients were mailed a questionnaire to assess satisfaction
with their medical care and with the nurse. RESULTS: Variation by the nurse from
the guidelines on surveillance endoscopy (1.9%) and the treatment of reflux
(1.3%) was rare. Most patients were very satisfied (score of 6 on 0-6-point
Likert scale) with overall medical care (88%), and patient education (76%), and
most patients did not think that increased physician involvement would improve
their care (93%). Ninety-seven percent of patients had control of reflux
symptoms. Two patients with long segment Barrett's esophagus (n = 67) developed
high grade dysplasia over 323 patient-yr of follow-up (1 of 162 patient-yr for an
annual incidence of 0.6%). No patients with short segment Barrett's esophagus (n
= 56) developed high grade dysplasia or adenocarcinoma over 172 patient-years of
follow-up. CONCLUSION: The registered nurse in our clinical setting effectively
administered clinical practice guidelines for the management of Barrett's
esophagus without clinically significant morbidity or patient dissatisfaction.
Before these results can be generalized to other settings, further studies will
need to be performed.
PMID- 9647017
TI - Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison
with mammographic surveillance for breast cancer.
AB - OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced
to detect malignancy in an early and curable stage. However, the cost
effectiveness of this practice has been questioned. To clarify this issue, we
undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in
Barrett's esophagus compared with mammography used to detect occult carcinoma of
the breast, a widely accepted cancer surveillance technique. METHODS: The rate of
esophageal adenocarcinoma detected by endoscopic surveillance was calculated for
Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and
compared with published rates. The rate of occult breast cancer detection was
calculated for all women undergoing surveillance mammography at the Duluth Clinic
for the year 1994 and compared with published rates. Costs for screening studies
and therapy for cancer treatment for both cancers were calculated based on
clinical results and assumptions regarding outcomes derived from published
reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149
patients with benign Barrett's esophagus was performed for a total of 510 patient
yr, during which time seven patients developed adenocarcinoma, an incidence of
one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50
of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were
comparable to published figures. The costs of detecting a case of adenocarcinoma
in Barrett's esophagus and occult breast cancer were $37,928 and $54,513,
respectively, and those for treatment resulting in cure were $83,340 and $83,292.
Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and
$57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with
Barrett's esophagus compares favorably with the common practice of surveillance
mammography to detect early breast cancer, and should therefore be considered to
be as cost-effective as surveillance mammography.
PMID- 9647018
TI - Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short
and long segment Barrett's esophagus.
AB - OBJECTIVE: Short segment Barrett's esophagus (SSBE) is defined as the presence of
specialized intestinal metaplasia (SIM) in the distal 2-3 cm of the esophagus.
Although gastroesophageal reflux and heartburn is very common in these patients,
the pathophysiology of the development of a short segment of SIM versus a longer
segment of Barrett's epithelium is not clear. The aim of this study was to assess
the extent of gastroesophageal reflux in short versus long segments of SIM.
METHODS: Of 203 consecutive patients undergoing endoscopy with two biopsies
performed just distal to the squamocolumnar junction, 28 patients were identified
as having SSBE as evidenced by SIM on biopsy. Twenty-two SSBE patients underwent
esophageal manometry and 24-h dual pH monitoring, and the results were compared
with 18 long segment Barrett's esophagus (LSBE) patients and 15 patients with
normal 24-h pH studies. RESULTS: SSBE and LSBE patients were significantly older
than normal subjects (p < 0.0001). Also, lower esophageal sphincter pressure was
significantly greater in SSBE patients compared with LSBE patients (12.3 +/- 1.6
vs 5.2 +/- 1.0 mm Hg,p < 0.0008). LSBE patients had a significantly lower distal
esophageal peristaltic amplitude as compared with normals (p < 0.012). At 5 cm
proximal to the LES, SSBE patients had significantly lower total 24-h pH scores,
percent upright and percent supine reflux as compared with LSBE patients.
Similarly, when measured at the proximal LES (0 cm), SSBE patients had
significantly lower 24-h pH scores when compared with LSBE patients (p < 0.03),
whereas percent upright and percent supine reflux were not significantly
different. Both LSBE and SSBE patients had a greater degree of GER measured at 5
cm above and just proximal to the LES when compared with normals. CONCLUSION: As
a group, SSBE patients have more competent LES sphincters and less
gastroesophageal reflux at 0 and 5 cm above the LES as compared with patients
with LSBE. These data indicate that the degree and length of acid exposure in the
esophagus are important factors in the pathogenesis of SIM involvement of the
esophagus.
PMID- 9647019
TI - Managing dyspepsia: what do we know and what do we need to know?
AB - OBJECTIVE: The conceptual revolution concerning the role of Helicobacter pylori
in the pathogenesis of peptic ulcer disease has raised the larger question of how
to integrate this new information into the management of patients with dyspepsia.
The aim of this research was to critically evaluate current knowledge about
dyspepsia and its management. METHODS: Relevant articles on dyspepsia were
identified from MEDLINE searches and from the bibliographies of identified
articles. Studies that contained information on the prevalence of dyspepsia,
endoscopic findings, and evaluations of alternative management strategies were
reviewed. RESULTS: By coupling H. pylori serological testing with clinical
factors such as age and nonsteroidal antiinflammatory drug use, strategies have
been developed that identify patients with organic disease. Although the use of
these strategies can reduce the volume of endoscopies, their effects on dyspepsia
symptoms are unknown. Computerized decision analysis models have been used to
evaluate the cost-effectiveness of alternative strategies. The indirect evidence
obtained from these models suggests that empiric therapy, guided by H. pylori
testing, may be the preferred approach. However, the models have been hampered by
the lack of information concerning dyspepsia symptoms, the primary health outcome
of the majority of patients seen in primary practice settings. CONCLUSIONS:
Currently, the knowledge needed to integrate H. pylori tests and antimicrobial
therapies into the management of patients with dyspepsia in primary practice
settings has not been developed. A pressing need exists for a randomized
controlled trial to evaluate alternative management strategies. In conducting
such a trial, valid, reliable instruments for measuring dyspepsia will be needed.
PMID- 9647020
TI - Eradication of Helicobacter pylori reduces the rate of duodenal ulcer rebleeding:
a long-term follow-up study.
AB - OBJECTIVES: The long-term efficacy of Helicobacter pylori eradication to reduce
the rate of recurrence of peptic ulcer bleeding is still uncertain. We evaluated
the rate of duodenal ulcer rebleeding for 48 months after H. pylori eradication.
METHODS: Thirty-two male patients with H. pylori infection and duodenal ulcer
bleeding were treated with omeprazole (40 mg/day for 4 wk), colloidal bismuth
(480 mg/day for 2 wk), amoxicillin (2 g/day for 1 wk), and metronidazole (750
mg/day for 1 wk), and followed up for 48 months. Endoscopy and tests for H.
pylori infection were repeated every year. RESULTS: Ulcer healed in all patients,
but H. pylori infection persisted or recurred in 11 patients. Within 48 months,
rebleeding occurred in nine (81.8%) of these patients, whereas the 21 patients
who were persistently negative for H. pylori infection remained asymptomatic
without rebleeding (0/ 21 = 0%, p < 0.002) during the whole follow-up.
CONCLUSIONS: Eradication of H. pylori can reduce the rate of duodenal ulcer
rebleeding for at least 4 yr, thus potentially modifying the natural history of
the disease.
PMID- 9647021
TI - Ulcer recurrence after gastric surgery: is Helicobacter pylori the culprit?
AB - OBJECTIVES: Helicobacter pylori is the most important cause of recurrent peptic
ulcer disease. However, its role in ulcer recurrence after peptic ulcer surgery
is unclear. We aimed at studying the prevalence and distribution of H. pylori in
patients who had undergone peptic ulcer surgery, and any association between H.
pylori infection and ulcer recurrence in these patients. METHODS: Patients with
previous vagotomy or partial gastrectomy presenting with dyspepsia or ulcer
bleeding were recruited. Ulcer recurrence was documented by endoscopy. Biopsy
specimens were taken from the gastric remnant and gastroenteric anastomosis in
patients with previous partial gastrectomy, or from the antrum and corpus in
vagotomized patients. H. pylori infection was detected by either a positive rapid
urease test or the presence of the bacteria on histology. RESULTS: Ninety-three
patients were studied; 73 patients (78%) had partial gastrectomy and 20 (22%) had
vagotomy with drainage. H. pylori infection was documented in 36 patients (49%)
in the gastrectomy group and in 13 (65%) in the vagotomy group. Thirty-six
patients in the gastrectomy group had recurrent ulcers and 15 (42%) of them had
H. pylori infection. Twelve patients in the vagotomy group had recurrent ulcers
and eight (67%) of them were H. pylori positive. The prevalence of H. pylori
infection did not differ between patients with or without ulcer recurrence.
CONCLUSION: H. pylori infection cannot account for ulcer recurrence after peptic
ulcer surgery.
PMID- 9647023
TI - Prevalence and etiology of gastroduodenal ulcer in HIV-positive patients: a
comparative study of 497 symptomatic subjects evaluated by endoscopy.
AB - OBJECTIVE: In 497 HIV-positive (+) patients with upper digestive tract symptoms,
23 (5%) had gastroduodenal ulcers (GDU) at upper endoscopy. METHODS: To establish
the causes of GDU in this setting, 16 of these patients who had had comprehensive
histological evaluation (group I) were compared with 20 HIV+ subjects with upper
gastrointestinal symptoms but without ulcer (group II), and with 16 seronegative
patients with GDU (group III). Eighty-one percent of group I subjects and 90% of
group II patients had C3 AIDS. The presence of gastritis and Helicobacter pylori,
fungi, mycobacteria, viruses (especially cytomegalovirus [CMV] and herpes simplex
[HSV]), and parasites was determined in all three groups by histopathological and
microbiological studies. RESULTS: The prevalence of chronic active gastritis was
13/16 (81%) in group I, 12/20 (60%) in group II, and 15/16 (94%) in group III. It
was associated with H. pylori in group III, and with opportunistic pathogens in
groups I and II and with none in group III. H. pylori was detected in 5/16
patients (31%) in group I, in 12/20 (60%) in group II, and 11/16 (69%) in group
III. Cytomegalovirus was histologically diagnosed in 8/16 patients (50%) in group
I and in 1/20 (5%) in group II. This virus was the only factor shown to be
significantly associated with GDU in these cases (p = 0.0046). Cryptosporidium
was found in 2/16 (12.5%) patients in group I, in 1/20 (5%) in group II, and in
none in group III. Differences between groups I and II were not statistically
significant. No other organisms were observed in the three groups. CONCLUSIONS:
Gastroduodenal ulcers were infrequent in HIV+ subjects with upper digestive tract
symptoms and CMV was the only organism significantly associated with GDU in HIV+
patients. Among HIV+ patients, H. pylori was an uncommon cause of ulcer. Among
HIV+ subjects with ulcer, chronic active gastritis was more common than H. pylori
and it was associated with other pathogens. Finally, HIV+ patients with GDU
should have endoscopic biopsies to detect opportunistic infections, especially
CMV, because H. pylori infection is uncommon.
PMID- 9647022
TI - Two-day quadruple therapy for cure of Helicobacter pylori infection: a
comparative, randomized trial.
AB - OBJECTIVE: We sought to compare a 2-day quadruple therapy with a 14-day triple
therapy in the treatment of Helicobacter pylori infection. METHODS: Eighty-one
consecutive patients with an endoscopically diagnosed peptic ulcer and
demonstrated infection by H. pylori were included in the study. Patients were
randomized to receive omeprazole 40 mg b.i.d., amoxicillin 2.5 g once daily,
metronidazole 500 mg t.i.d., and bismuth subcitrate 360 mg t.i.d. for 2 days,
followed by omeprazole 20 mg once daily for 6 additional days (Group 1) or a 14
day course of omeprazole 20 mg b.i.d., amoxicillin 1 g t.i.d., and metronidazole
500 mg t.i.d. (Group 2). Eradication was evaluated by antral biopsy and rapid
urease test at 2 months after therapy and by C13-urea breath test after a year.
RESULTS: Two patients were lost to follow-up at 2 months. Intention-to-treat
analysis showed that H. pylori infection was cured in 29 of 42 patients (69%; 95%
CI: 53-82%) in Group 1 versus 36 of 39 (92%; 95% CI: 78-98%) of patients in Group
2 (p = 0.009). Per-protocol analysis showed a cure rate of 71% (95% CI: 55-84%)
(29/41 patients) and 95% (95% CI: 81-99%) (36/38 patients), respectively (p =
0.007). Fifty-five of 65 cured patients returned 1 year after treatment (26 in
Group 1, 29 in Group 2). All but one in Group 2 remained cured. There were no
significant differences in compliance (88% in Group 1 versus 92% in Group 2) or
in the presence of side effects (27%; 95% CI: 15-43% versus 41%; 95% CI: 26-58%;
ns). CONCLUSION: Two-day quadruple therapy is significantly less effective than 2
wk triple treatment.
PMID- 9647024
TI - Percutaneous sonographic gastrostomy: method, indications, and problems.
AB - OBJECTIVES: This study evaluated the application of ultrasound (US) guidance in
the percutaneous placement of gastric feeding tubes in patients in whom
endoscopic placement of a nutrition tube is not possible. METHODS: Thirty-eight
patients with upper gastrointestinal obstruction were entered in a prospective
study with US-guided nutrition tube application. Feasibility of placement, side
effects, and nutritional states were monitored for a mean follow-up of 4 months.
RESULTS: Ultrasound allowed rapid puncture after filling of the stomach with
water through a nasal tube in 34/38 cases. In four cases a total upper
gastrointestinal obstruction required an initial stomach insufflation through a
direct puncture. Puncture-related major complications were not observed. Minor
complications during the observation time were one late dislocation, five cases
with broken material after about 6 months (four could be changed by using the
Seldinger technique), and two minor local infections. The nutrition through
feeding tubes stabilized body weight and body composition parameters. CONCLUSION:
The percutaneous sonographic gastrostomy (PSG) is a safe and minimally invasive
procedure for enteral nutrition in all cases with upper gastrointestinal
obstruction when endoscopic placement of a feeding tube is not possible.
Percutaneous sonographic gastrostomy may help to stabilize the nutritional
parameters and general condition in patients with malignant diseases.
PMID- 9647025
TI - Gastroesophageal reflux in patients fed by percutaneous endoscopic gastrostomy
(PEG): detection by a simple scintigraphic method.
AB - OBJECTIVES: Gastroesophageal scintigraphy has been described as a sensitive and
accurate way to detect and quantitate gastroesophageal reflux (GER). Our
objectives here were to evaluate the usefulness of a modified scintigraphic
technique in the detection of GER and lung aspiration in patients fed by
percutaneous endoscopic gastrostomy (PEG), and to assess the incidence of GER
after insertion of PEG. Further, we sought to examine whether or not the
underlying cause of dysphagia plays any significant part in the causation of GER.
METHODS: Twenty-two patients, 13 with neurological dysphagia and nine with
mechanical dysphagia, were studied. Each patient received 25 MBq of Tc-99m-tin
colloid in orange juice followed by 300 ml of normal saline through the PEG tube.
Dynamic and static images were taken immediately and at 4 h over esophagus,
stomach, and lungs. RESULTS: Twelve patients (10 with neurological dysphagia) had
GER and one had aspiration into the lungs. In all but one patient GER occurred in
the immediate postprandial period. CONCLUSIONS: Scintigraphy is useful in
assessing GER in PEG-fed patients. We also note that GER is a major problem in
patients with PEG, especially in those with neurological dysphagia.
PMID- 9647026
TI - Intravenous natural beta-interferon in white patients with chronic hepatitis C
who are nonresponders to alpha-interferon.
AB - OBJECTIVES: alpha-Interferons (alpha-IFN) have been shown to be effective in the
treatment of chronic viral C hepatitis, but their efficacy remains
unsatisfactory. Recently natural beta-interferon (beta-IFN) administered by
intravenous infusion has been used successfully. METHODS: To evaluate the
efficacy and safety of intravenous beta-IFN administration we treated 20 patients
with histologically proven chronic hepatitis C who were nonresponders to at least
two previous courses of alpha-IFN treatment. All patients received 6 million
units (MU) of natural human fibroblast beta-IFN by drip infusion, 6 times per wk
for 8 wk and were followed up for 6 months after suspension of treatment.
RESULTS: Five patients (25%) had response at the end of treatment; of these
patients only one had sustained response. Patients who responded to therapy had
lower, although not significantly, baseline levels of HCV RNA, compared with
nonresponders. Whereas mean viral load decreased during therapy, only two
patients were HCV RNA negative at the end of treatment, but none were at the end
of the follow-up period. Genotype 1 was found in 17 cases, genotype 2 was found
in one case, and a combination of genotypes 1b and 2a was found in the remaining
two cases. Therapy was well tolerated and beta-IFN administration was neither
interrupted nor its dosage reduced due to side effects in any of the patients.
CONCLUSIONS: Our study shows that intravenous beta-IFN is well tolerated and that
the modest results obtained may depend on the brevity of treatment. Consequently,
further studies are needed to define the optimum dose, schedule, and duration of
treatment to eradicate HCV infection.
PMID- 9647027
TI - Significance of elevated IgG anticardiolipin antibody levels in patients with
Budd-Chiari syndrome.
AB - OBJECTIVES: Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow
obstruction. Though hypercoagulable states are implicated in the causation of
BCS, the etiology remains unknown in most cases. Presence of anticardiolipin
antibodies (aCL) is a known cause of hypercoagulable state. We therefore studied
the frequency of IgG aCL in BCS. METHODS: Sera were obtained from 19 patients
with BCS, 50 healthy controls, 18 age- and gender-matched patients with
cirrhosis, and 15 patients with acute viral hepatitis. IgG aCL levels were
measured using a solid-phase enzyme immunoassay. Values exceeding mean + 2 SD of
healthy controls were taken as abnormal. RESULTS: Mean +/- SD IgG aCL levels (GPL
units) in the four groups were: healthy controls, 6.3 +/- 4.4; BCS, 13.8 +/- 13.3
(p < 0.05, compared with healthy controls); cirrhosis, 15.1 +/- 14.9 (p < 0.05,
compared with healthy controls and p = ns, compared with BCS patients); and acute
viral hepatitis, 5.0 +/- 2.5 (p = ns, compared with healthy controls). The levels
in BCS and cirrhosis patients were similar (p = ns). The number of patients with
elevated aCL was: healthy controls, 3/50; BCS, 6/19; cirrhosis, 7/18; and acute
viral hepatitis, 0/15. The number of patients with elevated IgG aCL was
significantly higher among patients with BCS and cirrhosis, compared with
controls (p = 0.03 and p = 0.002, respectively). CONCLUSIONS: Patients with BCS
had higher IgG aCL levels than healthy controls. However, as aCL levels were also
elevated in patients with cirrhosis, the pathogenetic role of IgG aCL in the
causation of BCS is doubtful.
PMID- 9647028
TI - Autoimmune conditions associated with primary biliary cirrhosis: response to
ursodeoxycholic acid therapy.
AB - OBJECTIVES: A variety of autoimmune conditions occur in association with primary
biliary cirrhosis. Among these conditions are sicca syndrome, Raynaud's
phenomenon, arthritis, and Hashimoto's thyroiditis. Information is sparse
regarding the prevalence and natural history of these conditions when associated
with primary biliary cirrhosis and their response to ursodeoxycholic acid
treatment. We evaluated the prevalence, natural history, and response to
ursodeoxycholic acid therapy of these conditions coassociated with primary
biliary cirrhosis. METHODS: One hundred-eighty patients with primary biliary
cirrhosis, enrolled in a prospective randomized controlled trial of
ursodeoxycholic acid (13-15 mg/ kg/day), were included. Patients were assessed at
study entry and annually. RESULTS: At entry, 77/180 patients (43%) had one of the
four conditions, and 18/180 patients (10%) had two or more conditions. Sicca
syndrome was the most common, occurring in 58/180 patients (32%). After 2 yr,
there was no difference between the treatment groups with regard to resolution or
spontaneous onset of these autoimmune features. Sicca syndrome was the most
common spontaneously developing condition (9% per yr). Sicca syndrome was the
most common associated autoimmune condition, present in one-third of our
patients. The associated conditions tended to improve over time, with a low rate
of spontaneously developing these conditions. Although ursodeoxycholic acid
therapy leads to improvement in the underlying liver disease, it did not appear
to influence either the development or resolution of these autoimmune features.
CONCLUSIONS: Although ursodeoxycholic acid is beneficial in the treatment of
primary biliary cirrhosis, it had no measurable effect on the autoimmune
conditions coassociated with the disease.
PMID- 9647029
TI - The effect of ciprofloxacin in the prevention of bacterial infection in patients
with cirrhosis after upper gastrointestinal bleeding.
AB - OBJECTIVES: Cirrhotic patients with upper gastrointestinal bleeding are prone to
bacterial infection. The aim of this study was to investigate the efficacy of
prophylactic intestinal decontamination with oral ciprofloxacin for the
prevention of bacterial infections in cirrhotic patients with upper
gastrointestinal bleeding. METHODS: A total of 120 cirrhotic patients with acute
upper gastrointestinal bleeding were enrolled. Sixty patients received
ciprofloxacin 500 mg twice daily given orally or through nasogastric tube
immediately after upper gastrointestinal endoscopic examination; drug
administration continued for 7 days. The remaining 60 patients, who received
placebo, served as controls. RESULTS: The incidence of proven bacterial infection
in the ciprofloxacin-treated group was significantly lower than that of placebo
group (10% vs 45%, p < 0.001). The incidences of bacteremia, spontaneous
bacterial peritonitis, and urinary tract infection in the ciprofloxacin-treated
group were significantly lower than those in the placebo group (0% vs 23%, 3.3%
vs 13%, and 5% vs 18%, respectively; p < 0.05, respectively). Multivariate
logistic regression analysis showed that a lack of prophylactic treatment with
ciprofloxacin and severity of cirrhosis were the independent significant
predictors for cirrhotic patients with acute gastrointestinal bleeding with
infection. CONCLUSIONS: Prophylactic intestinal decontamination with oral
ciprofloxacin is effective in the prevention of bacterial infections in patients
with cirrhosis who were suffering from acute upper gastrointestinal hemorrhage.
PMID- 9647030
TI - Beneficial effect of a bile acid resin binder on enteral feeding induced
diarrhea.
AB - OBJECTIVES: Diarrhea is a complication of enteral feeding, occurring in up to 68%
of critically ill patients. We hypothesized that prolonged fasting results in
abnormal bile acid homeostasis. Subsequent enteral feeding then causes a relative
luminal excess of bile acids, which leads to choleretic diarrhea. Hence, diarrhea
induced by enteral feeding should improve with the use of a bile acid binding
agent, such as Colestid Granules. METHODS: We evaluated the effect of Colestid on
enteral feeding-induced diarrhea in a double-blind placebo-controlled study.
Nineteen patients who were nil per os (NPO) for 5 days before initiation of
enteral feeding were enrolled in the study and treatment continued for 7 days.
The severity and frequency of diarrhea were quantified. Fecal bile acids were
measured enzymatically. Stool nutrient loss was measured by fat extraction,
microkjeldahl determination of nitrogen, and bomb calorimetry of dried fecal
specimens. RESULTS: Enteral feeding resulted in a high frequency of diarrhea
(95%) at some time during the observation period. The majority of episodes of
diarrhea in both groups were of low volume. Colestid significantly decreased the
prevalence and severity of diarrhea. Colestid had no significant effect on fecal
calorie or nutrient losses. The average bile acid concentration in the stool
increased significantly after enteral feeding. CONCLUSION: Enteral feeding
induced diarrhea is, at least in part, due to malabsorption of bile acids. The
bile acid resin binding agent Colestid improves diarrhea induced by enteral
feeding.
PMID- 9647031
TI - A double-blind placebo-controlled pilot study of glutamine therapy for abnormal
intestinal permeability in patients with AIDS.
AB - OBJECTIVES: Up to 20% of patients with AIDS have abnormal intestinal permeability
(IP). Glutamine seems to play an important role in preventing the increase in IP
and loss of intestinal mucosal mass associated with total parenteral nutrition,
and may be superior to glucose for oral rehydration in the setting of intestinal
infection. This study was designed to see if supplemental glutamine could alter
the abnormal IP of AIDS. METHODS: Randomly chosen patients with AIDS from the
Jacobi Medical Center human immunodeficiency virus (HIV) clinic underwent IP
testing using lactulose and mannitol. Those with abnormal IP were enrolled.
Duodenal biopsies were performed with a Crosby capsule and the patients were
randomized in a double-blind fashion to receive placebo or glutamine (4 g/day or
8 g/day) for 28 days, after which intestinal permeability tests and duodenal
biopsies were repeated. Intestinal morphology was graded by ratio of villus
height to crypt depth, and by degree of inflammation. RESULTS: All patients
complied with the therapy and there were no dropouts or reported side effects.
The results showed less worsening of IP with the 4 g/day dose, compared with
placebo. At the 8 g/day dose, there was stabilization of IP and improved
absorption of mannitol. Intestinal morphology and inflammation did not change in
any group. CONCLUSIONS: These results, although not significant, suggest a trend
towards improved IP and enhanced intestinal absorption with glutamine. Glutamine
doses of at least 20 g/day may be necessary to improve IP. We recommend further
studies at higher doses and for longer durations.
PMID- 9647032
TI - Thyroid and celiac disease: clinical, serological, and echographic study.
AB - OBJECTIVE: We sought to reevaluate the prevalence of thyroid dysfunction and
thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were
studied as controls. Both patients and controls were from Sardinia, Italy.
METHODS: Diagnosis of celiac disease was made on the basis of clinical history,
presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies,
antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was
confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was
performed in 36/47 celiac patients. Thyroid was evaluated by palpation and
echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH),
and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by
radioimmunoassays. RESULTS: The prevalence of anti-TPO was higher in celiac
patients (29.7%) than in healthy controls (9.6%) (p < 0.001) and thyroid
echography frequently displayed (42.5%) a hypoechogenic pattern. Five anti-TPO
positive celiac patients were hypothyroid (two overt, three subclinical). A
higher but not significantly different prevalence of anti-TPO (3/7 = 42.8%) was
found in celiac patients displaying the DQB1*0502 genotype, when compared with
the remaining patients (8/29 = 27.6%). CONCLUSIONS: An elevated prevalence of
clinical and subclinical autoimmune thyroid autoimmunity was found in Sardinian
celiac patients, especially in those displaying the DQB1*0502 genotype; this
finding could be related to a particular genetic background of the Sardinian
population.
PMID- 9647033
TI - P53 protein immunohistochemical expression in colonic adenomas with and without
associated carcinoma.
AB - OBJECTIVES: P53 protein immunohistochemical (IHC) expression was investigated in
a series of colonic adenomas and carcinomas to determine the p53
immunohistochemical expression of adenomas in general compared with carcinomas,
the difference in staining pattern between adenomas with associated carcinoma and
those without associated carcinoma, and the difference in p53 staining in the
usual adenomas (low-grade dysplasia) compared with those harboring high-grade
dysplasia. METHODS: The study involved a series of 20 adenomas without concurrent
carcinoma (group 1 adenoma), 29 adenomas with concurrent carcinoma (group 2
adenoma), and 20 carcinomas. Sections of the paraffin-embedded tissues were
stained with DO-7 p53 monoclonal antibody after microwave antigen-retrieval
method. Cases with nuclear staining in > or = 20% of the tumor cells were
considered positive. RESULTS: Analysis of results showed that 65% of carcinomas
and 37% of all adenomas were reactive with p53 IHC staining (p = 0.03). With
respect to the adenomas, 30% of group 1 and 41% of group 2 adenomas were reactive
for p53 protein (p = 0.42). CONCLUSIONS: Our data demonstrate a statistically
significant higher p53 expression rate in colonic carcinomas than in adenomas,
and that adenomas with concurrent carcinomas are more frequently p53 positive
than those without concurrent carcinoma, but this was not statistically
significant. Also, p53 expression is more frequent and intense in adenomas with
high-grade dysplasia (10/20, 50%) than in ordinary adenomas with low-grade
dysplasia (8/29, 28%), which suggests a strong correlation between the degree of
dysplasia in colonic neoplasia and p53 expression pattern.
PMID- 9647034
TI - Psychological and physical stress induce differential effects on human colonic
motility.
AB - OBJECTIVE: Stress modulates gut function, but whether the type of stressor
influences colonic motor activity is unclear. The motor patterns and regional
variations are also poorly understood. Our aim was to determine the effects of
psychological and physical stress on colonic motility. METHODS: Ambulatory
colonic manometry was performed by placing a six-sensor probe up to the mid
transverse colon, without sedation, in 12 healthy subjects. Five hours later, a
dichotomous listening test (psychological stress) was performed, which was
preceded by listening to a narrative passage (control); recovery entailed
listening to relaxing music (1 h each). Subsequently, intermittent hand immersion
in cold (4 degrees C) water (physical stress) was performed, preceded by hand
immersion in warm (37 degrees C) water (1/2-h each). Colonic pressure activity
and cardiovascular responses were measured throughout the study. RESULTS: When
compared with the control period, both stressors induced a greater number of
pressure waves (p < 0.05), and the area under the curve (p < 0.01), but only
physical stress increased (p < 0.05) pulse rate and blood pressure. There were no
regional differences in colonic motility. During recovery, the motor activity
returned to baseline after physical stress, but remained high after psychological
stress. Psychological stress induced more (p < 0.05) propagated contractions,
whereas physical stress induced more (p < 0.05) simultaneous contractions.
CONCLUSIONS: Both stressors enhanced colonic motor activity, but psychological
stress induced a prolonged response with propagated activity and without
appreciable autonomic response. Thus, colonic motor responses may vary depending
on the stressor.
PMID- 9647035
TI - Palliation of obstructing gastric carcinoma with metal stents through a
gastrostomy.
AB - Gastric cancer is the world's second most common malignancy. In the U.S.,
patients present with advanced disease, and surgery with curative intent accounts
for only 30% of gastric malignancies. Palliative surgery has significant
morbidity and mortality. Recently, there have been encouraging reports of self
expanding endoprostheses in obstructing gastrointestinal neoplasms. We report a
case of a 70-yr-old woman with inoperable outlet stenosis secondary to a mucinous
infiltrating adenocarcinoma involving nearly the entire stomach, except the
anterior wall, which provided a percutaneous access site for gastrostomy and
subsequently successful management of outlet obstruction with metallic stents.
PMID- 9647036
TI - Pseudogastroparesis as a presentation of adenocarcinoma of the proximal jejunum.
AB - Establishing the presence of adenocarcinoma of the small bowel is exceedingly
difficult. Survival is contingent on prompt diagnosis. We describe a patient with
an atypical presentation of jejunal adenocarcinoma visualized via small bowel
enteroclysis. She was referred with "gastroparesis," based on both a
radionucleotide scan that revealed markedly delayed gastric emptying and a
"normal" small bowel series. A markedly abnormal scintigraphic study and a
negative small bowel series does not exclude disease of the small intestine and
should provide the impetus to further pursue the possibility of an obstructing
lesion. The enteroclysis is a relatively safe and effective study in the
preoperative diagnosis of small bowel tumors.
PMID- 9647037
TI - Hepatoma with severe non-islet cell tumor hypoglycemia.
AB - We report a 22-yr-old male patient with chronic hepatitis B and a large, well
differentiated hepatoma who developed episodes of symptomatic fasting
hypoglycemia, which were caused by paraneoplastic secretion of unprocessed "big"
insulin-like growth factor-II. Initially, the patient presented with normal liver
function, which deteriorated during the clinical course. Therapeutic attempts to
reduce tumor mass failed and the patient subsequently died because of metastases
of the hepatoma. The pathophysiology of non-islet cell tumor hypoglycemia,
differential diagnosis, and therapeutic options are discussed.
PMID- 9647038
TI - Typhoid fever complicated by acute renal failure and hepatitis: case reports and
review.
AB - Four cases of typhoid fever complicated by both acute oliguric renal failure and
hepatitis are presented. Two patients had type II hepatitis according to criteria
proposed by Khosla et al. (30) with hepatomegaly, hyperbilirubinaemia and
markedly elevated asparate transaminase (AST); the others had type III hepatitis,
characterized clinically and biochemically by profound jaundice, hepatomegaly,
hepatic encephalopathy (one case only), hyperbilirubinemia and markedly elevated
serum AST. Renal biopsy was not performed in any of our patients. However, a
combination of proteinuria and abnormal urinary sediments containing red cell
casts and granular casts, as noted in these patients, is considered highly
suggestive of glomerulonephritis. Although isolated renal failure and hepatitis
with hepatomegaly and deranged liver enzyme values have been reported previously
in typhoid fever, their occurrence simultaneously in the same patient in
distinctly rare, having been reported only twice in the English language
literature.
PMID- 9647039
TI - Gastric angiomyolipoma: a previously undescribed cause of upper GI hemorrhage.
AB - Angiomyolipomas are rare lesions often arising in the kidney. We describe the
first documented case of symptomatic gastric angiomyolipoma.
PMID- 9647040
TI - Transient protein-losing enteropathy associated with cytomegalovirus infection in
a noncompromised host: a case report.
PMID- 9647041
TI - Gastroesophageal reflux--is it hereditary?
PMID- 9647042
TI - Surgical and medical therapies for GERD--can we see into the future?
PMID- 9647043
TI - Endoscopic ultrasound, ampullary tumors, and minimally invasive therapy: a cost
saving combination?
PMID- 9647044
TI - Polymyositis and esophageal carcinoma.
PMID- 9647045
TI - Vertical transmission of Helicobacter pylori: different transmission route.
PMID- 9647046
TI - Botulinum toxin injection in achalasia before myotomy.
PMID- 9647047
TI - Aeromonas as a cause of segmental colitis.
PMID- 9647048
TI - Severe leukocytosis with neutrophilia (leukemoid reaction) in alcoholic
steatohepatitis.
PMID- 9647049
TI - Cutaneous vasculitis as the initial manifestation of Crohn's disease in a
pediatric patient.
PMID- 9647050
TI - Colon cancer in young persons of East African descent.
PMID- 9647051
TI - Long-term clinical outcome after transcervical thymectomy for myasthenia gravis.
AB - BACKGROUND: We reviewed the long-term clinical outcome after transcervical
thymectomy for generalized myasthenia gravis without thymoma in 52 patients who
had this procedure at The Toronto Hospital between 1977 and 1986, and compared
the results with those reported after more radical surgical approaches. METHODS:
Preoperative and postoperative patient evaluations were based on a modified
Osserman classification. We defined complete remission as asymptomatic with
normal strength and without medications for myasthenia gravis. The complete
remission rate was selected as the best measure for comparison between different
surgical approaches. RESULTS: The 52 patients were followed up for a mean of 8.4
years (+/-6.1 years [standard deviation]). The preoperative mean Osserman grade
was 2.7 compared with 0.4 at final follow-up. Complete remission occurred in
44.2% of patients. Similar results are reported after transsternal thymectomy.
CONCLUSIONS: Comparable results after transcervical and transsternal thymectomy
favor the use of the less radical approach.
PMID- 9647052
TI - Cytostatic lung perfusion by use of an endovascular blood flow occlusion
technique.
AB - BACKGROUND: Different modalities of cytostatic lung perfusion were compared
regarding plasma and tissue drug concentrations to assess the efficacy of an
endovascular blood flow occlusion technique. METHODS: A cytostatic lung perfusion
study with doxorubicin hydrochloride was performed on large white pigs (n = 12).
Plasma and tissue concentrations of doxorubicin were compared for isolated lung
perfusion with open cannulation (ILP), blood flow occlusion perfusion with open
cannulation of the pulmonary artery alone (BFO), and intravenous drug
administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was
performed by endovascular balloon catheterization of the pulmonary artery
(endovascular BFO). The 3 animals in this group were used to compare the
doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes
after 1 month. RESULTS: The mean lung tissue doxorubicin concentration at the end
of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO
(p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01).
Whereas doxorubicin was not detectable in the plasma in the ILP group,
concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and
from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue
concentration was not significantly different after BFO than i.v. perfusion (1.1
+/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO
group, balloon-blocked pulmonary artery perfusion was successfully performed in
all animals, and after 1 month, lung tissue showed no cytostatic-induced
histologic changes. CONCLUSIONS: Compared with ILP, BFO cytostatic lung perfusion
produced an insignificantly higher lung-tissue concentration, corresponding to a
sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels
during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may
be a promising technique for repeated cytostatic lung perfusion.
PMID- 9647053
TI - Multiple primary cancers in esophageal squamous cell carcinoma: incidence and
implications.
AB - BACKGROUND: The occurrence of multiple primary cancers in the aerodigestive tract
is a well-known phenomenon. This study aims to elucidate the incidence and the
therapeutic and prognostic implications of a nonesophageal primary cancer in
patients with squamous cell carcinoma of the esophagus. METHODS: Between 1982 and
1996, 1,055 patients with esophageal squamous cell carcinoma treated at our
institution were reviewed for the presence of an additional primary cancer. The
effects of the nonesophageal cancer on treatment of the esophageal carcinoma and
survival were analyzed. RESULTS: Among 1,055 patients, 114 nonesophageal primary
cancers were documented in 100 patients (9.5%), 70% of which were aerodigestive
tract cancers. Forty-seven patients had antecedent tumors and 43 had synchronous
tumors. Treatment strategies for esophageal carcinoma in these patients were
similar to patients without multiple tumors, not influenced by the nonesophageal
tumor except in 6 patients. The overall survival of patients with antecedent
tumors, synchronous tumors, and without multiple tumors was similar (median
survival, 8.6, 8.5, and 8.8 months, respectively) (p = 0.84). Subsequent primary
cancers developed in 10 patients (0.9%), 9 of them with previous curative
resection of esophageal cancer, and all died of the subsequent cancer.
CONCLUSIONS: There is a high incidence of multiple primary cancers in patients
with esophageal carcinoma but the treatment and prognosis of these patients are
primarily determined by the esophageal carcinoma itself. Subsequent cancer is,
however, a significant cause of death among patients cured of esophageal
carcinoma.
PMID- 9647054
TI - Minimally invasive valve operations.
AB - BACKGROUND: To reduce the morbidity from valvular heart operations, a right
parasternal approach was introduced. We report our initial experience with the
procedure. METHODS: From January 1996 through July 1996, 115 patients underwent
primary isolated valve procedures. One hundred (85%) patients underwent the
operation through a right parasternal incision. RESULTS: There was one hospital
death secondary to a stroke on the fifth postoperative day. Three patients (two
with aortic valve operations and one having a mitral valve procedure) required
conversion to sternotomy. Mean aortic occlusion time was 71 minutes; mean
cardiopulmonary bypass time was 93 minutes. Mean stay in the intensive care unit
was 27 hours and mean hospital postoperative stay was 5.7 days. Seventy-seven
percent of the patients did not receive blood transfusions. Comparison with
median sternotomy demonstrated a reduction in both postoperative length of stay
and direct hospital costs. CONCLUSIONS: We conclude that this minimally invasive
approach is safe for a variety of valve procedures and is effective in reducing
surgical trauma and cost.
PMID- 9647055
TI - Therapeutic angiogenesis with basic fibroblast growth factor: technique and early
results.
AB - BACKGROUND: Patients not amenable to complete myocardial revascularization by
conventional methods present a difficult clinical problem. Here we present the
early results and technical considerations of the administration of basic
fibroblast growth factor for the induction of collateral growth using heparin
alginate slow-release devices in patients undergoing coronary artery bypass
grafting. METHODS: Eight patients were enrolled. Patients were candidates if they
had at least one graftable obstructed coronary artery and at least one major
arterial distribution not amenable to revascularization, a serum creatinine level
less than 3 mg/dL, ejection fraction greater than 0.20, and estimated operative
mortality of less than 25%. During conventional coronary artery bypass grafting,
10 heparin-alginate devices, each containing either 1 microg or 10 microg of
basic fibroblast growth factor, were implanted in the epicardial fat in multiple
regions of the unrevascularizable territory and also in the distal distribution
of a grafted or patent artery. RESULTS: There was no mortality and no evidence of
renal, hematologic, or hepatic toxicity during follow-up. Three months after the
operation, all patients remain free of angina. Seven patients were examined with
stress perfusion scans. Three patients had clear enhancement of perfusion to the
unrevascularized myocardium, 1 patient had a new fixed defect, and 3 had minimal
overall change but had evidence of new small, fixed perfusion defects. Seven
patients had improved or similar myocardial contractile function (ejection
fraction at 3-month follow-up = 0.53 +/- 0.22 versus 0.47 +/- 0.14
preoperatively). One patient suffered a perioperative myocardial infarction in
the area of basic fibroblast growth factor administration. CONCLUSIONS: This
preliminary study demonstrates the safety and technical feasibility of
therapeutic angiogenesis with basic fibroblast growth factor delivered by heparin
alginate slow-release devices. Further studies examining the safety, clinical
efficacy, and long-term results are ongoing.
PMID- 9647056
TI - Risk of reoperative valve replacement for failed mitral and aortic bioprostheses.
AB - BACKGROUND: One factor influencing the choice of mechanical versus bioprosthetic
valves is reoperation for bioprosthetic valve failure. To define its operative
risk, we reviewed our results with valve reoperation for bioprosthetic valve
failure. METHODS: Records of 400 consecutive patients having reoperative mitral,
aortic, or mitral and aortic bioprosthetic valve replacement from January 1985 to
March 1997 were reviewed. RESULTS: Reoperations were for failed bioprosthetic
mitral valves in 219 patients, failed aortic valves in 153 patients, and failed
aortic and mitral valves in 28 patients. Including 26 operations (6%) for acute
endocarditis, 153 operations (38%) were nonelective. One hundred nine patients
(27%) had other valves repaired or replaced, and 72 (18%) had coronary bypass
grafting. The incidence of death in the mitral, aortic, and double-valve groups
was respectively, 15 (6.8%), 12 (7.8%), and 4 (14.3%); and the incidence of
prolonged postoperative hospital stay (>14 days) was, respectively, 57 (26.0%),
41 (26.8%), and 8 (28.6%). Only 7 of 147 patients (4.8%) having elective,
isolated, first-time valve reoperation died. Multivariable predictors (p < 0.05)
of hospital death were age greater than 65 years, male sex, renal insufficiency,
and nonelective operation; and predictors of prolonged stay were acute
endocarditis, renal insufficiency, any concurrent cardiac operation, and elevated
pulmonary artery systolic pressure. CONCLUSIONS: Reoperative bioprosthetic valve
replacement can be performed with acceptable mortality and hospital stay. The
best results are achieved with elective valve replacement, without concurrent
cardiac procedures.
PMID- 9647057
TI - The Ross procedure: shorter hospital stay, decreased morbidity, and cost
effective.
AB - BACKGROUND: The Ross procedure has become an accepted and sometimes preferred
alternative to mechanical aortic valve replacement. One criticism of the Ross
procedure is that it may have a higher operative mortality, morbidity, and cost.
Several groups have shown that this operation can be performed safely with less
than 3% mortality. The issue of higher cost has not been resolved. In this
retrospective study we compared a consecutive group of patients undergoing the
Ross procedure with an age- and disease-matched group of patients who underwent
mechanical aortic valve replacement. METHODS: From 1993 to 1996, 22 consecutive
adult patients (age range, 20 to 57 years; mean, 38 +/- 14 years) underwent the
Ross procedure. Twenty-seven patients (age range, 17 to 57 years; mean, 41 +/- 10
years) underwent mechanical aortic valve replacement between 1991 and 1996. The
hospital cost (in 1996 dollars) and postoperative length of stay were calculated
for each patient using Transition I, a hospital-wide cost accounting system.
RESULTS: There was no hospital mortality in either group. The incidence of
significant valve-related complication was 5% (1/22 patients) in the Ross
procedure group and 22% (6/27 patients) in the mechanical valve group. There were
two late deaths in the group with mechanical aortic valve replacement. The length
of stay for the Ross procedure group was 5.9 +/- 2.1 days, versus 8 +/- 1.85 days
for the mechanical valve group (p < 0.01). The mean hospital costs were not
significantly different, $23,140 +/- $7,825 for the mechanical valve group and
$23,226 +/- $6,960 for the group having the Ross procedure. CONCLUSIONS: The data
from this review demonstrate that the Ross procedure can be done safely, with
short hospital stays, decreased morbidity, and costs comparable with those of
standard mechanical aortic valve replacement in patients with isolated aortic
valve disease.
PMID- 9647058
TI - Intermittent antegrade tepid versus cold blood cardioplegia in elective
myocardial revascularization.
AB - BACKGROUND: The ideal temperature for blood cardioplegia administration remains
controversial. METHODS: Fifty-two patients who required elective myocardial
revascularization were prospectively randomized to receive intermittent antegrade
tepid (29 degrees C; group T, 25 patients) or cold (4 degrees C; group C, 27
patients) blood cardioplegia. RESULTS: The two cohorts were similar with respect
to all preoperative and intraoperative variables. The mean septal temperature was
higher in group T (T, 29.6 degrees +/- 1.1 degrees C versus 17.5 degrees +/- 3.0
degrees C; p < 0.0001). After reperfusion, group T exhibited significantly
greater lactate and acid release despite similar levels of oxygen extraction (p <
0.05). The creatine kinase-MB isoenzyme release was significantly lower in group
T (764 +/- 89 versus 1,120 +/- 141 U x h/L; p < 0.04). Hearts protected with
tepid cardioplegia demonstrated significantly increased ejection fraction with
volume loading, improvement in left ventricular function at 12 hours, and
decreased need for postoperative inotropic support (p < 0.05). The frequency of
ventricular defibrillation after cross-clamp removal was lower in this cohort (p
< 0.05). There were no hospital deaths, and both groups had similar postoperative
courses. CONCLUSIONS: Intermittent antegrade tepid blood cardioplegia is a safe
and efficacious method of myocardial protection and demonstrates advantages when
compared with cold blood cardioplegia in elective myocardial revascularization.
PMID- 9647059
TI - Is atrial fibrillation resulting from rheumatic mitral valve disease a proper
indication for the maze procedure?
AB - BACKGROUND: There are a few patients without detectable atrial contraction
despite restoration of atrial rhythm after the maze procedure for atrial
fibrillation (AF) associated with mitral valve disease. METHODS: From January
1995 to March 1997, 29 consecutive patients with AF associated with mitral valve
disease underwent our modified maze procedure combined with mitral or other valve
operations. The causes of mitral valve disease were rheumatic mitral stenosis (n
= 22) and nonrheumatic mitral regurgitation (n = 7). The 17 patients with
postoperative atrial rhythm were divided into group I with rheumatic mitral
stenosis (n = 10), and group II with mitral regurgitation of nonrheumatic origins
(n = 7). RESULTS: Seventeen patients regained atrial rhythm, 2 patients had
junctional rhythm, and another 10 remained in AF. Between the group of patients
with restoration of atrial rhythm and that of patients remaining in AF,
significant differences were found in the percentage with rheumatic disease,
history of AF, and maximum f-wave voltage. The postoperative peak velocity of the
atrial filling wave to peak velocity of early filling wave ratio for the left
atrium measured using Doppler echocardiography was 0.25 in group I, which was
significantly lower than that (0.42) in group II. CONCLUSIONS: Reconsideration of
the indications for the maze procedure for AF associated with rheumatic mitral
stenosis may thus be reasonable, particularly for cases in which replacement
using a prosthetic valve is necessary, but we believe that patients with
nonrheumatic mitral valve disease, especially those able to undergo
reconstructive operations, are the best candidates for the maze procedure.
PMID- 9647060
TI - Lethal postoperative coronary artery spasm.
AB - BACKGROUND: Coronary artery spasm in the immediate postoperative period after a
coronary operation is recognized infrequently. Its severity is variable and
manifestations unpredictable. The diagnosis is usually made by an awareness of
the possibility and thereafter by exclusion of other causes of myocardial
ischemia. An opportunity for a positive diagnosis is rarely available. METHODS:
The case reports of 3 patients with similar presentations of ischemic heart
disease and with severe manifestations of coronary artery spasm in the
postoperative period are presented. RESULTS: All 3 patients were women aged 55 to
60 years. All had single-vessel coronary artery disease involving the left
anterior descending artery and underwent a left internal mammary artery bypass
graft. Severe manifestations of myocardial ischemia of abrupt onset developed
approximately 7 hours postoperatively in each patient. One patient died of severe
hemodynamic deterioration from which resuscitation was unsuccessful. Another
sustained a large anterior myocardial infarction despite graft patency. The third
patient was supported by an intraaortic balloon pump and made a full recovery.
CONCLUSIONS: The early diagnosis of coronary artery spasm is achieved by an
awareness of the condition. The institution of early appropriate management may
prevent its consequences.
PMID- 9647061
TI - Risk factors for death after heart transplantation: does a single-center
experience correlate with multicenter registries?
AB - BACKGROUND: Risk factors for death after heart transplantation (Tx) are
frequently documented from multicenter registries. Although this information is
helpful, it reflects a whole range of experiences and results, and may not
translate to a particular center. This study was performed to (1) evaluate pre-Tx
factors affecting mortality in a single-center experience, and (2) compare these
factors with risk factors obtained from multicenter registry reports. METHODS:
Review of our transplant database between January 1984 and December 1995
identified 405 adults who received a primary heart Tx. Multiple factors were
analyzed, including demographics, Tx era, cytomegalovirus status, United Network
for Organ Sharing status of recipient, presence of pulmonary hypertension,
previous cardiac operations, mechanical ventilation or circulatory support,
ischemia time, number of rejection episodes, and preoperative flow cytometry
crossmatching. RESULTS: One- and 5-year survival rates were 87.8% and 73.4%,
respectively (Kaplan-Meier). Contrary to multicenter registry reports, our data
indicate that reoperative procedures, left ventricular assist device support,
increasing donor and recipient age, and ischemia time up to 4.2 hours are not
risk factors for death after Tx. Likewise, mode of donor death is not a risk
factor affecting outcome. Significant risk factors for mortality identified by
multivariate analysis included early transplant era (1984 to 1989; p = 0.002),
female donor (p = 0.042), cytomegalovirus-seropositive donor (p = 0.048), high
pulmonary vascular resistance (p = 0.018), and intraaortic balloon pump support
(p = 0.03). It also identified a positive B-cell flow cytometry crossmatch (p =
0.015) to be a risk factor with univariate analysis. CONCLUSIONS: Our data
identify a group of recipients, reportedly at high risk in multicenter
registries, who are not at increased risk of death after Tx. This information
supports the growing experience with older donors and recipients and with bridged
transplants, and has allowed us to expand our donor pool. These prognostic
factors at evaluation allow more liberal selection of patients and donors for
transplantation.
PMID- 9647062
TI - Terminal warm blood cardioplegia improves cardiac function through microtubule
repolymerization.
AB - BACKGROUND: To elucidate the mechanisms responsible for the beneficial effects of
terminal warm blood cardioplegia, we studied dynamic change in microtubules
induced by cold cardioplegia followed by rewarming. Further, we investigated the
relationship between cardiac function and morphologic changes in microtubules
caused by hyperkalemic, hypocalcemic warm cardioplegia during initial
reperfusion. METHODS: In protocol 1 isolated rat hearts were perfused at 37
degrees C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac
arrest at 10 degrees C, hearts were reperfused at 37 degrees C with one of two
buffers: group C, 60-minute reperfusion with KHB (K+, 5.9 mmol/L; Ca2+, 2.5
mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K+, 15
mmol/L; Ca2+, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB.
Cardiac function after reperfusion was determined as a percentage of the
prearrest value. In protocol 2 hearts were perfused at 37 degrees C with KHB
containing colchicine (10(-5) mol/L) for 60 minutes. RESULTS: There was
spontaneous contractile recovery after 10 minutes of initial reperfusion in
hearts from group TC as well as improved cardiac function after 15, 30, and 60
minutes of reperfusion compared with that in group C. Immunohistochemical
staining and immunoblot analysis demonstrated microtubule depolymerization during
hypothermic cardiac arrest and complete repolymerization after 10 minutes of
reperfusion with warm buffers in both groups. Colchicine-induced microtubule
depolymerization is associated with deterioration of cardiac function.
CONCLUSIONS: One mechanism responsible for improved cardiac function mediated by
terminal warm blood cardioplegia is the restart of contraction after complete
microtubule repolymerization.
PMID- 9647063
TI - Hyperglycemia during normothermic cardiopulmonary bypass: the role of the kidney.
AB - BACKGROUND: Hyperglycemia commonly occurs during cardiopulmonary bypass. We
studied the quantitative impact of glucose input and its renal excretion on
hyperglycemia during cardiopulmonary bypass. METHODS: The quantity of glucose
infused and metabolite and hormone concentrations in plasma, as well as oxygen
consumption, carbon dioxide production, and renal glucose excretion, were
determined before, during, and after cardiopulmonary bypass in 8 patients.
RESULTS: Hyperglycemia (14 to 29 mmol/L) was accompanied by an increase in plasma
insulin levels. The degree of hyperglycemia was directly related to the amount of
glucose infused. The rate of oxygen consumption did not decrease and the rate of
urea appearance (gluconeogenesis) did not rise. Despite a very high filtered load
of glucose, there was very little glucosuria, indicating a markedly enhanced
renal absorption of glucose. CONCLUSIONS: Hormonal and metabolic factors permit
the development of hyperglycemia during cardiopulmonary bypass but its severity
depends on the quantity of glucose infused and, what appears to be a new finding,
a markedly enhanced renal reabsorption of filtered glucose. Thus the kidney plays
an important role in the development of severe hyperglycemia during
cardiopulmonary bypass.
PMID- 9647064
TI - Left main coronary artery patch angioplasty: midterm experience and follow-up
with spiral computed tomography.
AB - BACKGROUND: Patch angioplasty is an alternative surgical technique in cases of
left main coronary artery stenosis. We report our experience with this technique,
with particular mention of the use of spiral computed tomography for the follow
up of our patients. METHODS: In this retrospective study we analyzed the results
obtained in all 7 patients (3 women and 4 men) who were operated on with this
technique in our institution between July 1992 and August 1994. Five consenting
patients also underwent graft patency assessment with spiral computed tomographic
imaging. RESULTS: The operation was uneventful in all patients and there were no
hospital deaths. Two patients required reoperation (1 of them dying at
reoperation), 1 because of restenosis of the graft and 1 because of the presence
of a new stenosis in the proximal anterior descending coronary artery. The
remaining 5 patients were asymptomatic after 51 +/- 2 months. Spiral computed
tomographic images were artifacted and of poor quality. CONCLUSIONS: Patch
angioplasty of the left main coronary artery can be a valuable therapeutic method
in selected cases. Conventional spiral computed tomography is not an optimal
noninvasive method for the assessment of graft patency.
PMID- 9647065
TI - Silent aspiration after coronary artery bypass grafting.
AB - BACKGROUND: "Silent" aspiration was recognized to be a more frequent complication
at this hospital in patients who have had coronary artery bypass grafting than in
the general surgical population. METHODS: A case-control retrospective study
covering a 4.5-year period was conducted to determine risk factors for pharyngeal
dysfunction resulting in silent aspiration. RESULTS: Significant predictors of
silent aspiration were age, history of cerebral vascular disease, insulin
dependent diabetes mellitus, myocardial infarction, and chronic obstructive
pulmonary disease. Intraaortic balloon pump and number of units of fresh-frozen
plasma were the only independent intraoperative factors associated with silent
aspiration in a model using continuous variables directly. Cold fibrillation was
used in 7 of 53 study cases but no control patients, so it could not be modeled.
Postoperative complications occurring with greater frequency included neurologic
complications, adverse pulmonary outcomes, repeat surgical interventions,
infection, and death. Using an Aspiration Risk Profile developed from the
retrospective study, in a detailed prospective study of 10 patients, 3 of 4
patients with postoperative dysphagia had objective evidence of stroke.
CONCLUSIONS: These findings suggest that postoperative coronary artery bypass
graft dysphagia may be the result of intraoperative cerebral injury, and that
careful postoperative clinical evaluation of coronary artery bypass graft
patients with risk factors may result in early diagnosis of pharyngeal
dysfunction with the goals of preventing silent aspiration and reducing
morbidity, mortality, and hospital cost.
PMID- 9647066
TI - Apoptosis is involved in acute cardiac allograft rejection in rats.
AB - BACKGROUND: Allograft rejection remains a major obstacle to long-term survival in
heart transplantation. Recent studies have demonstrated that apoptotic cell death
may occur in acute allograft rejection. The purpose of this study was to
determine whether apoptotic cell death is involved in rat cardiac allograft
rejection through both the perforin/granzyme pathway and the Fas/Fas ligand (Fas
L) pathway. METHODS: Groups of Lewis (RT1(1)) rats underwent heterotopic heart
transplantation from disparate DA (RT1a) or syngeneic Lewis rats. The cardiac
grafts were harvested 1, 3, or 5 days after transplantation and analyzed for
apoptotic cell death using DNA nick-end labeling, immunocytochemistry, and
electron microscopy. In addition, the expression of granzyme B, perforin, Fas,
and Fas-L messenger RNA were analyzed by reverse transcriptase-polymerase chain
reaction. RESULTS: Apoptotic cell death of cardiac myocytes was prominent in
allografts on day 5 after transplantation. Fas gene transcripts were
constitutively expressed in both syngeneic and allogeneic grafts, whereas
expression of Fas-L was only upregulated in allografts with ongoing rejection.
Granzyme B and perforin gene expression were also upregulated in allografts with
ongoing rejection. CONCLUSIONS: These results suggest that myocyte apoptosis
through both the perforin-granzyme pathway and the Fas-Fas-L pathway may be
involved in cardiac allograft rejection in rats.
PMID- 9647067
TI - Myocardial distribution of antegrade cold crystalloid and tepid blood
cardioplegia.
AB - BACKGROUND: Tepid blood (TB) cardioplegia combines the improved rheologic
characteristics and the augmented oxygen and substrate delivery of blood
cardioplegia with the advantages of moderate hypothermia. In addition, the
intramyocardial distribution of continuous TB cardioplegia may also be better
than intermittent cold crystalloid (CC) cardioplegia. We sought to compare the
distribution of TB and CC cardioplegia at varying infusion pressures. METHODS: In
situ, isolated canine hearts were randomized to antegrade, continuous TB (28
degrees C, n = 8) or intermittent CC (n = 8) cardioplegia infused at 50, 75, and
100 mm Hg. The regional distribution of cardioplegia at each pressure was
measured by 15-microm colored microspheres. Cardioplegia distribution was
measured from three areas each of the right ventricle (inflow, outflow, and apex)
and the left ventricle (anterior, lateral, and posterior). Left ventricular
samples were subdivided into subepicardial, midmyocardial, and subendocardial.
RESULTS: Delivery of cardioplegia to all areas of the right and left ventricles
showed a linear pressure-flow relationship over the range of pressures tested.
Right ventricular distribution was two-thirds of that to the left ventricle, and
left ventricular subepicardial distribution was approximately one half of
subendocardial flow in both groups at all delivery pressures. However, the
subendocardial to subepicardial ratio was significantly greater with TB
cardioplegia than with CC cardioplegia. Transmural right ventricular cardioplegia
flow was comparable in both groups. In contrast, left ventricular distribution of
CC cardioplegia was greater than TB cardioplegia at all three pressures tested.
CONCLUSIONS: The pressure-flow relationship in both CC and TB cardioplegia is
linear in both the right and left ventricular myocardium over clinically
applicable delivery pressures. The distribution of cardioplegia to the right
ventricle is not altered by increased pressure.
PMID- 9647068
TI - Levels of troponin I and cardiac enzymes after reinfusion of shed blood in
coronary operations.
AB - BACKGROUND: Reinfusion of shed blood after coronary artery bypass grafting might
increase the levels of cardiac enzymes with consequent difficulties in the
diagnosis of perioperative myocardial infarction. METHODS: Thirty consecutive
patients undergoing coronary artery bypass grafting who bled at least 400 mL
within the first 4 hours after operation underwent reinfusion of shed blood.
Thirty consecutive patients who were not autotransfused served as control. All
patients underwent enzyme determination (total creatine kinase, MB fraction,
lactate dehydrogenase, and troponin I) in the shed blood and in circulating blood
preoperatively, at arrival in the intensive care unit, and 6, 24, and 48 hours
after operation. RESULTS: The shed blood contained significantly higher
concentration of cardiac enzymes than the circulating blood at all time intervals
(p = 0.0001). The levels of creatine kinase, its MB fraction, and lactate
dehydrogenase in circulating blood were significantly elevated in patients
receiving autotransfusion up to 24 hours after autotransfusion. The blood levels
of troponin I were not significantly different between the two group of patients
at all time points. The percent fraction of MB did not increase after
autotransfusion. CONCLUSIONS: The measurement of cardiac troponin I is a useful
marker for the diagnosis of perioperative myocardial infarction in patients
undergoing transfusion of shed blood after coronary operation.
PMID- 9647069
TI - Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by
coronary bypass grafts.
AB - BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA)
versus saphenous vein (SV) after coronary artery bypass grafting are well
documented. Higher production rates of vasodilating and platelet-inhibiting
mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact
on its long-term durability and resistance to coronary artery graft disease. For
the right gastroepiploic artery (RGEA) marked release of protective mediators is
reported as well. The vasodilating effect of cyclic guanosine monophosphate
(cGMP) released after stimulation by atrial natriuretic peptide might serve as
another graft protective system. The aim of the present study was to determine
cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge.
METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded
during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial
natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was
determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates
of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were
higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of
atrial natriuretic peptide led to a statistically significant increase of cGMP
release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3
fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05).
CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA
and SV produces more extracellular cGMP when stimulated by atrial natriuretic
peptide. This effect might support the cGMP-mediated protective properties of
nitric oxide and could underline the extraordinary suitability of the IMA as a
bypass conduit.
PMID- 9647070
TI - HeartMate left ventricular assist device as bridge to heart transplantation.
AB - BACKGROUND: Because of the limited supply of donor hearts, prospective recipients
continue to die while on the waiting list for heart transplantation. Use of long
term mechanical circulatory support devices as a bridge to transplantation may
reduce this mortality. However, with the present state of technology, continued
clinical evaluation of the various long-term, mechanical circulatory support
devices available is mandatory. METHODS: Sixteen patients were bridged with the
HeartMate left ventricular assist device (LVAD) to heart transplantation for New
York Heart Association functional class IV cardiac failure. Twelve pneumatic and
six electric devices were used. The mean cardiac index and the mean pulmonary
vascular resistance of the patient cohort were 1.71 x min(-1) x m(-2) and 3.1
Wood units, respectively. RESULTS: The mean LVAD support time per transplanted
patient was 237 days, with a cumulative LVAD support time of about 7.2 years.
Bleeding was the main operative and postoperative complication. Two patients
suffered from neurologic complications and there were two major incidents of
device malfunction. Twelve patients (75%) now have received a transplant, 3 (19%)
are awaiting a transplant, and in 1 patient (6%), the device was explanted after
spontaneous left ventricular recovery. Eleven of the 12 patients who received a
transplant are alive and doing well. The HeartMate LVAD gave adequate circulatory
support over extended periods of time and reversed the vital organ dysfunction.
Since the start of the LVAD program, only 1 patient has died on our heart
transplantation waiting list, compared to nine deaths in the 2 preceding years.
CONCLUSIONS: The HeartMate LVAD bridge to heart transplantation can be performed
with low post-LVAD implantation and posttransplantation mortality and offers 1-
and 2-year posttransplantation actuarial survival rates comparable to those for
nonbridged heart transplant recipients.
PMID- 9647071
TI - Discrepancies between sizer and valve dimensions: implications for small aortic
root.
AB - BACKGROUND: Precise labeling of sizer and valve diameters is crucial for optimal
valve selection especially in the small aortic root. This study examines the
accuracy of manufacturers' markings on small aortic prostheses and sizers.
METHODS: Sizer and valve dimensions of 22 different mechanical aortic prostheses
(19 to 23 mm) were evaluated by caliper micrometer measurements. RESULTS: Nearly
all sizers exceeded their marked dimensions by up to 1.0 mm. Measured tissue
annulus diameters for 19-mm-labeled valves varied between 18.3 and 19.6 mm, for
21-mm valves from 20.5 to 21.6 mm, and for 23-mm valves from 22.4 to 23.5 mm,
respectively. The orifice areas ranged from 1.5 to 2.06 cm2 for 19-mm valves,
from 2.0 to 2.55 cm2 for 21-mm valves, and from 2.4 to 3.09 cm2 for 23-mm valves,
respectively. CONCLUSIONS: Actual sizer dimensions and tissue annulus diameters
of various small mechanical aortic prostheses varied considerably from their
marked diameters. These differences should be considered to ensure the optimal
prosthesis selection for each patient.
PMID- 9647072
TI - Reversibility of cardiac dysfunction after valve replacement in elderly patients
with severe aortic stenosis.
AB - BACKGROUND: The role of aortic valve replacement for aortic stenosis has not been
fully defined in terms of the postoperative reversibility of cardiac dysfunction
and pulmonary hypertension in elderly patients. METHODS: Cardiac function,
assessed by radioisotope ventriculography and catheterization data, was evaluated
before and after operation, and their results were compared between preoperative
and postoperative data in each group of younger patients (<69 years, group I, n =
29) and elderly patients (> or =70 years, group II, n = 21). RESULTS: One month
postoperatively the peak ejection rate determined by radioisotope
ventriculography improved significantly in comparison with the preoperative value
in elderly patients (preoperatively, 228 +/- 38 versus postoperatively, 319 +/-
116% end-diastolic volume per second, p < 0.05), although their preoperative peak
ejection rate was severely depressed. The postoperative peak filling rate of the
elderly group was not completely reversible to almost normal value, whereas that
of the younger group was completely reversible. Early diastolic peak filling rate
(one-third peak filling rate) was not reversible in both two groups. Pulmonary
hypertension in the elderly patients was reversible to postoperative almost
normal pulmonary artery pressure despite the severity of aortic stenosis
(systolic pulmonary artery pressure preoperatively, 37 +/- 16 mm Hg versus
postoperatively, 25 +/- 5 mm Hg, p < 0.02; diastolic pulmonary artery pressure
preoperatively, 15 +/- 6 mm Hg versus postoperatively, 10 +/- 4 mm Hg, p < 0.05).
CONCLUSIONS: Both cardiac dysfunction, reflected by reduction of peak ejection
rate, and pulmonary hypertension in elderly patients with severe aortic stenosis
were reversed, reaching almost normal values 1 month after operation.
PMID- 9647073
TI - Significance of serum S100 release after coronary artery bypass grafting.
AB - BACKGROUND: S100 protein has been suggested to be a serum marker for cerebral
complications after cardiac operation and extracorporeal circulation. The aim of
this study was to characterize the S100 release pattern after extracorporeal
circulation in 515 consecutive patients undergoing coronary artery bypass
grafting. METHODS: Clinical variables and outcome were prospectively registered.
The cerebral outcome was determined by clinical examination. S100 was measured at
the end of extracorporeal circulation, and after 5, 15, and 48 hours. RESULTS:
After operation, 13 patients had stroke, 12 had delayed awakening, and 17 had
encephalopathy. Early S100 release, immediately after extracorporeal circulation,
was associated with age and perfusion time, but not with cerebral outcome.
However, S100 release after 5 to 48 hours was associated with cerebral
complications and risk factors for such outcome. Patients with stroke had higher
S100 levels after 15 to 48 hours. A subset of patients with renal failure had
overall higher S100 levels at 5 hours. CONCLUSIONS: Early and late S100 release
indicate different mechanisms for release and emphasizes the potential power of
this new biochemical marker for cerebral damage.
PMID- 9647074
TI - Cerebral emboli and serum S100beta during cardiac operations.
AB - BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage
in a number of clinical settings. The purpose of this investigation was to
determine the correlation between cerebral microemboli and S100beta levels during
cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to
measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were
divided into five time periods: (1) incision to aortic cannulation; (2) aortic
cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release;
(4) cross-clamp release to decannulation; and (5) decannulation to chest closure.
The level of S100beta (n = 156) was measured at baseline, at the end of
cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release.
RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time,
cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary
bypass time was univariately associated with S100beta level, it became
nonsignificant in a multivariable model that included age and cross-clamp time.
CONCLUSIONS: The correlation of S100beta level with emboli measured during
cannulation (time period 2) supports the hypothesis that cannulation is a high
risk time period for cerebral injury.
PMID- 9647075
TI - Cardiotomy suction: a major source of brain lipid emboli during cardiopulmonary
bypass.
AB - BACKGROUND: Brain injury remains a significant problem in patients undergoing
cardiac surgery assisted by cardiopulmonary bypass (CPB). Autopsy brain specimens
of patients after cardiac operations with CPB reveal numerous acellular lipid
deposits (10 to 70 microm) in the microvasculature. We hypothesize that these
small capillary and arterial dilatations result from a diffuse inflammatory
response to CPB or from emboli delivered by the bypass circuit. This study was
undertaken to determine which aspect of CPB is most clearly associated with these
dilatations. METHODS: Thirteen dogs were studied in four groups: group I (n = 3),
right-heart CPB; group II (n = 2), lower-extremity CPB; group III (n = 3),
hypothermic CPB; and group IV (n = 5), hypothermic CPB with cardiotomy suction.
All dogs in all groups were maintained on CPB for 60 minutes and then euthanized.
Brain specimens were harvested, fixed in ethanol, embedded in celloidin, and
stained with the alkaline phosphate histochemical technique so that dilatations
could be counted. RESULTS: All dogs completed the protocol. The mean density of
dilatations per square centimeter for each group was as follows: group I, 1.77 +/
0.77; group II, 4.17 +/- 1.65; group III, 4.54 +/- 1.69; and group IV, 46.5 +/-
14.5. In group IV (cardiotomy suction), dilatation density was significantly
higher than in group III (hypothermic cardiopulmonary bypass) (p = 0.04) and all
other groups (p = 0.04). CONCLUSIONS: Blood aspirated from the surgical field and
subsequently reinfused into dogs undergoing CPB produces a greater density of
small capillary and arterial dilatations than CPB without cardiotomy suction,
presumably because of lipid microembolization.
PMID- 9647076
TI - Posterior distribution of infarcts in strokes related to cardiac operations.
AB - BACKGROUND: Stroke complicates cardiac surgical procedures in a substantial
number of patients. The mechanism of stroke is predominantly embolic, although
hypoperfusion may play a role. The aim of this study was to determine whether
radiologic appearances in this population were consistent with an embolic cause.
METHODS: We reviewed computed tomographic scans and medical records in 24
patients who suffered stroke after cardiac operation. Stroke was evident at 24
hours in 19 patients (79%). Infarcts were multiple in 16 and single in 3 patients
(group 1). The remaining 5 patients suffered stroke beyond 24 hours and had
single infarcts on computed tomographic scan (group 2). RESULTS: In group 1, 15
patients (79%) had bilateral cerebellar infarcts, 4 (74%) had posterior cerebral
artery infarcts, 10 (53%) had posterior watershed infarcts, and 11 patients (58%)
had middle cerebral artery branch infarcts. The mean number of vascular
territories involved was 5.1 (range, 1 to 10). Mobile atheromatous plaque was
present in the ascending aorta or arch in 5 of 9 patients (56%) in group 1. In
group 2, stroke occurred in close association with atrial or ventricular
fibrillation in 3 of 5 patients (60%). CONCLUSIONS: In patients with radiologic
evidence of infarction, perioperative strokes after cardiac operation are
typically multiple, and involve the posterior parts of the brain, consistent with
atheroembolization. Delayed strokes may be attributable to cardiogenic embolism.
PMID- 9647077
TI - Biomechanical study of sternal closure using rigid fixation techniques in human
cadavers.
AB - BACKGROUND: We believe rigid plate fixation may be superior to wire fixation in
sternal closure, as rigid fixation used in the craniofacial skeleton has shown
greater stability, lower postoperative pain, and accelerated bone healing. We
hypothesize that sterna fixed with titanium plates are more stable mechanically
than sterna fixed with wires. METHODS: The sterna from human cadavers were used
in this two-phased study. Phase I compared wires to four-hole titanium straight
plates. Phase II compared wires to four-hole titanium custom H plates. The sterna
were tested biomechanically using all fixation methods. RESULTS: Phase I showed
no statistically significant difference in the stiffness or lateral displacement
between the wired and straight plated sterna. Phase II showed a statistically
significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05)
in the custom plated sterna over the wired sterna. CONCLUSIONS: Our results
showed that custom titanium H plates were superior to wire fixation. Furthermore,
our results established the importance of plate configuration in sternal
fixation. Our study may have beneficial clinical implications, as decreased
motion at the sternotomy site could mean less postoperative pain, a decreased
incidence of infection, and accelerated bone healing.
PMID- 9647078
TI - Radiofrequency and cryoablation of atrial fibrillation in patients undergoing
valvular operations.
AB - BACKGROUND: Previous studies have shown that the maze operation can restore sinus
rhythm and atrial transport function in patients with chronic atrial
fibrillation. The purpose of this study was to test the feasibility of the
application of radiofrequency and cryoablation as an alternative to the classic
maze operation. METHODS: Twelve patients undergoing mitral valve procedures were
included in this study. Radiofrequency and cryoablation were applied to create
lesions in both atria to simulate the classic maze operation. RESULTS: There were
two surgical deaths. At the mean follow-up of 10.25 months for the remaining 10
patients; 6 were in sinus rhythm, 2 in atrial rhythm, 1 in paroxysmal atrial
tachycardia, and 1 in atrial fibrillation. Doppler echocardiography at 6-month
follow-up showed emergence of biatrial transport function in 3 patients and right
atrial contractility in 8. At 12-month follow-up of 5 patients, Doppler
echocardiography showed biatrial transport function in 3 and right atrial
contractility in 4. CONCLUSIONS: Our modified maze procedure during valvular
operation is effective for achieving an acceptable success rate to restore sinus
rhythm and atrial transport function in patients with chronic atrial
fibrillation.
PMID- 9647079
TI - Bilateral thoracoscopic minimally invasive direct coronary artery bypass grafting
using internal thoracic arteries.
AB - BACKGROUND: Single-vessel coronary artery bypass grafting of the left internal
mammary artery (ITA) to the left anterior descending coronary artery using a
minithoracotomy has been shown to produce excellent results with a very low
mortality. However, this procedure cannot be used in patients with double- or
triple-vessel disease. Our goal was to develop a minimally invasive direct
coronary artery bypass grafting procedure without cardiopulmonary bypass for
patients with multivessel disease. METHODS: Both ITAs were thoracoscopically
harvested using video imaging. Limited bilateral anterior thoracotomies were
performed in the fourth intercostal spaces, thus exposing the right coronary
artery and the left anterior descending coronary artery. The right ITA-right
coronary artery and ITA-left anterior descending coronary artery anastomoses were
performed without cardiopulmonary bypass using 8-0 polypropylene sutures.
RESULTS: This procedure was successfully performed in 3 patients. The patients
were extubated in the operating room. Postoperative angiographic studies showed
patent left ITA and right ITA grafts. CONCLUSIONS: Bilateral thoracoscopic
minimally invasive direct coronary artery bypass grafting can be used to treat
patients with a proximally diseased left anterior descending coronary artery and
right coronary artery. Bilateral thoracoscopic ITA harvesting is a less invasive
surgical technique that may become an option for the management of multivessel
coronary artery disease.
PMID- 9647080
TI - Effects of cardiomyoplasty on right ventricular filling during volume loading.
AB - BACKGROUND: Although cardiomyoplasty (CMP) is thought to improve ventricular
systolic function, its effects on ventricular diastolic function are not clear.
Especially the effects on right ventricular diastolic filling have not been fully
investigated. Because pericardial influences are more pronounced in the right
ventricle than in the left ventricle, CMP with its external constraint may
substantially impair right ventricular diastolic filling. METHODS: Fourteen
purebred adult beagles were used in this study. Seven underwent left posterior
CMP, and 7 underwent a sham operation with a pericardiotomy and served as
controls. Four weeks later, the hemodynamic effects of CMP were evaluated by
heart catheterization before and after volume loading (central venous infusion of
10 mg/kg of 4.5% albumin solution for 5 minutes). RESULTS: In the CMP group, mean
right atrial pressure and right ventricular end-diastolic pressure increased
significantly from 3.1 +/- 1.2 mm Hg to 6.1 +/- 2.0 mm Hg (p < 0.001) and from
4.0 +/- 1.8 mm Hg to 9.6 +/- 2.5 mm Hg (p < 0.001), respectively. Volume loading
in the control group did not significantly increase either variable. Right
ventricular end-diastolic volume and stroke volume did not change significantly
(from 53 +/- 9.3 mL to 60 +/- 9.0 mL and from 20 +/- 2.3 mL to 21 +/- 3.2 mL,
respectively) in the CMP group. In the control group, however, right ventricular
end-diastolic volume and stroke volume increased significantly from 45 +/- 7.7 mL
to 63 +/- 14 mL (p < 0.05) and from 18 +/- 4.3 mL to 22 +/- 4.2 mL (p < 0.05),
respectively. CONCLUSIONS: These results suggest that CMP may reduce right
ventricular compliance and restrict right ventricular diastolic filling in
response to rapid volume loading because of its external constraint.
PMID- 9647081
TI - Postischemic function and protein kinase C signal transduction.
AB - BACKGROUND: The protective effects of myocardial preconditioning may occur by way
of multiple mechanisms, with G-protein-mediated protein kinase C (PKC)
translocation as a final common pathway. In this study we investigate the
pharmacologic induction of preconditioning, by PKC translocation, using PKC
agonists/antagonists to reveal its effects on contractile function after
myocardial ischemia. METHODS: Langendorff-perfused rabbit hearts received: (1)
control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC
agonist); (4) 1,2-s,n-dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5)
chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG-chelerythrine followed by
a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute
reperfusion period. The period of ischemia was chosen so as to allow for
improvement by appropriate agonists. To observe metabolic changes, tissue
nucleotides and nucleosides were measured. Membrane and cytosolic fractions of
PKC were determined by an anti-PKC antibody directed against the PKC delta
isozyme. Lactate levels and myocardial pH were measured. RESULTS: The PKC
agonists DOG and acetylcholine showed the greatest recovery of developed pressure
(68% +/- 2%, 60% +/- 9%, respectively). Although pH, lactate, and nucleotide
levels were similar between groups at all times, myocyte PKC translocation
demonstrated 25% of PKC delta isoforms on cell membrane sites during baseline,
which shifted to 67% delta 17% with unprotected ischemia. DOG mimicked this shift
with 58% delta 12% of PKC delta isoforms on membranes, which was also blocked by
chelerythrine to 35% +/- 7%. CONCLUSIONS: These data demonstrate that PKC
translocation results in improved postischemic function, not by alteration of
energetics or metabolism, and deserves further investigation.
PMID- 9647082
TI - Expression of vascular adhesion molecules in saphenous vein coronary bypass
grafts.
AB - BACKGROUND: Adhesion of blood elements to the endothelium is an important step in
the development of vein graft disease. This study examines the expression of
vascular adhesion molecules on explanted saphenous vein bypass grafts. METHODS:
Immunocytochemical staining was performed using explanted saphenous vein grafts
from 28 patients. Antibodies against the endothelial markers CD31, von Willebrand
factor, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E
selectin were used. RESULTS: Staining for CD31 and von Willebrand factor
demonstrated the presence of endothelial cells in the lumen and the vasa vasorum.
Expression of intercellular adhesion molecule-1 was variable between grafts,
whereas vascular adhesion molecule-1 and E-selectin were almost always absent on
the luminal endothelium. In contrast, the endothelium of the vasa vasorum stained
positively for intercellular adhesion molecule-1 and vascular adhesion molecule
1, and was also seen on nonendothelial cells within the vessel wall. Expression
of these adhesion molecules did not vary with the severity of vein graft disease.
CONCLUSIONS: This study highlights the blood vessels in the adventitia as
possible sites for the adhesion and migration of cells into the vessel wall.
PMID- 9647083
TI - The role of platelet-activating factor in regional myocardial ischemia
reperfusion injury.
AB - BACKGROUND: This swine model was designed to elucidate the role of platelet
activating factor in regional myocardial ischemia-reperfusion injury. METHODS: In
groups 1 and 2 (n = 12 each), the left anterior descending coronary artery was
ligated for 60 minutes to induce regional myocardial ischemia followed by 6 hours
of reperfusion. Group 1 received the platelet-activating factor antagonist TCV
309 before ischemia, whereas group 2 did not. Group 3 (n = 3) had a sham
operation. RESULTS: Animals in group 2 exhibited significant (p < 0.05)
hemodynamic instability and myocardial depression during the reperfusion period.
Despite preventive measures, 7 of the 12 animals experienced severe dysrhythmias
in the form of atrial and ventricular fibrillation leading to cardiac arrest. In
contrast, animals in group 1 in whom the effects of platelet-activating factor
were blocked by the specific platelet-activating factor receptor antagonist TCV
309 were hemodynamically stable and had significantly (p < 0.05) better
myocardial function. This significant difference in global myocardial function
between the groups was observed in the presence of similar morphologic findings
and regional myocardial function. CONCLUSIONS: These results suggest that
platelet-activating factor has a definite influence on global myocardial
dysfunction associated with regional myocardial ischemia-reperfusion injury.
PMID- 9647084
TI - Total simultaneous repair of coarctation and intracardiac pathology in adult
patients.
AB - BACKGROUND: Thoracic aortic coarctation accompanied by a second surgically
reparable lesion is a rare combination in the adult patient. The simultaneous
operative management of both lesions is desirable because of the higher morbidity
and mortality that would occur with staged procedures. METHODS: We describe the
simultaneous operative management in three adult patients with coarctation and a
second cardiac lesion. All 3 patients had intrapericardial ascending aorta
descending aorta bypass and concomitant repair of a cardiac lesion. The attendant
repairs in the 3 patients, respectively, were aortic valve replacement,
orthotopic heart transplantation, and coronary artery bypass grafting. RESULTS:
Double arterial cannulation, retrograde cardioplegia, large-bore aorto-aortic
bypass grafts, and early use of alpha-agonists to stabilize systemic pressure
were all key to ensuring safe conduct of the operation. Each patient had an
essentially uneventful postoperative course. CONCLUSIONS: Thoracic coarctation
and concomitant cardiac pathology can be safely and readily managed with a single
stage approach involving cardiac repair and extraanatomic ascending aorta
descending aorta bypass grafting. A review of the English-language literature of
patients managed similarly is included.
PMID- 9647085
TI - Cerebral and systemic embolization during left ventricular support with the
Novacor N100 device.
AB - BACKGROUND: Patients undergoing implantation of left ventricular assist systems
(LVAS) are prone to thromboembolic complications. We analyzed the incidence,
clinical findings, and outcome of neurologic and systemic thromboembolic events
(TE) in patients with the Novacor N100 LVAS. In a subset of patients,
transcranial Doppler sonography was used to detect microembolic signals. METHODS:
Thirty-six patients underwent implantation of a Novacor N100 LVAS for various
reasons. The surgical procedure was elective in 18 patients and scheduled on an
urgent or emergency basis in another 18 patients. The assist period lasted from
17 to 336 days (109 +/- 88 days); 22 patients were forwarded to heart
transplantation after being supported for 140 +/- 87 days. RESULTS: Clinical
cerebral embolism was evident in 17 patients (47%). Thromboembolic events were
singular in 8 and multiple in 9 patients; in the latter up to 10 TE occurred
(mean +/- SD, 1.4 +/- 2 TE). Leading neurologic symptoms were unilateral
hemiplegia in 11, as well as ocular symptoms and aphasia in 12 patients each.
Noncerebral TE were detected in 4 patients, 2 of whom underwent an emergency
operation for intestinal and iliac artery occlusion. The incidence of TE did not
correlate strongly with the interval of LVAS support. Cerebral computed
tomography confirmed lesions in 58% of patients. Transcranial Doppler sonography
detected microembolic signals on 67% of all recordings, with the microembolic
signals being more frequent on days with clinically manifest TE. The outcomes
were good, as only 2 patients suffer from neurologic sequelae. CONCLUSIONS:
Thromboembolism is still a major threat for patients with LVAS implantation.
Neurologic sequelae are frequent but have a favorable prognosis, and systemic
complications occur considerably less often. Patient selection, adequate
anticoagulation, and transcranial Doppler sonography may help to reduce the
incidence of TE.
PMID- 9647086
TI - Improvement in esophageal varices and liver histology postoperatively in Budd
Chiari syndrome.
AB - BACKGROUND: In the past 17 years, 32 patients with Budd-Chiari syndrome were
treated by reconstruction of the occluded inferior vena cava and reopening of the
hepatic veins under femoro-femoral normothermic extracorporeal partial bypass.
The mean follow-up was 8 years (range, 1.5 to 17 years). METHODS: To evaluate the
benefits of our operative procedure, we compared the preoperative, early
postoperative, and late postoperative endoscopic appearance of the esophageal
varices and the histologic findings of the liver tissue obtained intraoperatively
and at a later date. RESULTS: The esophageal varices found preoperatively in 29
patients (90.6%) had disappeared in 7 patients by the time of discharge, and in 2
patients they disappeared 4 to 7 years after surgery. In the remaining 20
patients, the grade of the esophageal varices was reduced markedly. Histologic
examination of the liver showed cirrhosis in 22 patients, fibrosis in 9 patients,
and severe congestion in 1 patient. Inspection of the liver in the late
postoperative period (in 10 patients) showed improvement in centrilobular
congestion and no increase in interlobular fibrosis. CONCLUSIONS: Gradual and
steady improvement of esophageal varices and hepatic fibrosis can be achieved
after our operative procedure.
PMID- 9647087
TI - Complement activation and cytokine generation after modified Fontan procedure.
AB - BACKGROUND: The modified Fontan procedure separates the systemic and pulmonary
circulations in patients born with a functional single ventricle. Delayed
recovery is frequently observed after this procedure. It was our hypothesis that
complement activation or cytokine generation may contribute to the
pathophysiology of this problem. METHODS: We measured activated complement C3,
thromboxane B2, interleukin-6, and tumor necrosis factor-alpha levels by
immunoassay in 16 patients undergoing Fontan procedure. Patient plasma samples
were obtained preoperatively, on initiation of cardiopulmonary bypass, after
administration of protamine, and 1, 4, 8, and 24 hours postoperatively. RESULTS:
There was no early or late mortality in this cohort of patients. Low cardiac
output developed in 3 of 16 patients, and pleural effusions developed in 5. The
median length of hospital stay was 9 days. Activated complement C3 levels
increased from a baseline of 1,486 +/- 564 to 4,600 +/- 454 ng/mL after
cardiopulmonary bypass and administration of protamine, and returned to baseline
by 24 hours. The level of interleukin-6 increased from 42 +/- 32 to 176 +/- 22
pg/mL and at 24 hours remained elevated at 71 +/- 15 pg/mL. Neither thromboxane
B2 nor tumor necrosis factor-alpha levels increased significantly. CONCLUSIONS:
The data demonstrate threefold to four-fold increases in activated complement C3
and interleukin-6, indicating that both humoral and cellular systems are
affected. It is our conclusion that complement and cytokine activation may
contribute to the delayed recovery observed after Fontan procedure.
PMID- 9647088
TI - Clinical results of the staged Fontan procedure in high-risk patients.
AB - BACKGROUND: For high-risk Fontan candidates, the introduction of a bidirectional
Glenn shunt before total cavopulmonary connection (a two-staged strategy) may
extend the indications for the Fontan procedure. The clinical results of the two
staged and one-staged Fontan procedure were thus reviewed and compared. METHODS:
Between November 1991 and July 1996, the two-staged strategy was performed in 40
high-risk Fontan candidates with a mean interval of 17.2 months after introducing
the bidirectional Glenn shunt (staged group). We considered a young age (<2
years), high mean pulmonary arterial pressure (> or =20 mm Hg), high pulmonary
vascular resistance (> or =3 Wood units), small pulmonary artery (Nakata index
<200 mm2/m2), atrioventricular valve incompetence (> or = moderate), distortion
of pulmonary artery, anomalous pulmonary venous return, and poor ventricular
function as risk factors for the successful completion of Fontan circulation.
During the same period, 68 patients underwent the modified Fontan procedure in a
one-step fashion (primary group). RESULTS: In the staged group after the
bidirectional Glenn shunt, the mean pulmonary arterial pressure and ventricular
end-diastolic pressure were both found to have decreased significantly to the
same level as those in the primary group, whereas the pulmonary artery
demonstrated a significantly smaller size than that in the primary group.
Operative morbidity was similar in both groups. Operative mortality was also
similar and low in both groups (1.5% in the primary group and 0% in the staged
group). CONCLUSIONS: A bidirectional Glenn shunt was found to be a useful interim
palliation in high-risk Fontan candidates. This two-staged strategy may extend
the operative indications for the Fontan procedure.
PMID- 9647089
TI - Pulmonary root replacement with the Freestyle stentless aortic xenograft in
growing pigs.
AB - BACKGROUND: The stentless xenograft with its favorable hemodynamic performance on
the left side of the heart seems an attractive, readily available alternative for
the reconstruction of the right ventricular outflow tract in children. METHODS:
To assess its function in a preclinical animal investigation, we replaced the
pulmonary root with a Freestyle stentless aortic xenograft in 18 piglets of 26.6
+/- 3.2 kg weight. The animals were allowed to grow as much as possible and
slaughtered when symptoms of heart failure developed or body weight reached more
than 160 kg. All valve explants were analyzed by gross examination and
photography and, in 4 representative pigs, by histologic examination. RESULTS:
Fourteen animals died prematurely after 2 weeks to 11 months. Twelve xenograft
explants showed thick, immobilized, large nodular structures as cuspal remnants
causing significant stenosis. At microscopy, large cuspal masses of degenerating
collagen and fibrin and various inflammatory cells were frequently found. In the
growing pig, most of the xenografts implanted in the pulmonary position showed
early degeneration causing severe stenosis. CONCLUSIONS: Use of this valve for
right ventricular outflow tract reconstruction in children cannot be recommended.
PMID- 9647090
TI - Brain damage and myocardial dysfunction: protective effects of magnesium in the
newborn pig.
AB - BACKGROUND: Brain damage is associated with myocardial dysfunction resulting from
excessive release of endogenous catecholamines and Ca2+ overload. Magnesium ion,
a natural Ca2+ blocker, has recently been recognized as a myoprotective agent.
METHODS: Myocardial function was assessed in 3- to 7-day-old piglets from
pressure-volume data (obtained by the conductance catheter/micromanometer
technique) before and for 4 hours after ligation of the aortic arch vessels and
was correlated with ultrastructural changes. Group a (n = 6) received MgSO4
immediately after induction of brain damage for 4 hours, whereas group b (n = 6)
did not receive MgSO4 and served as control. RESULTS: In both groups after
induction of brain damage, there was a significant (p < 0.05) increase in end
systolic elastance and preload-recruitable stroke work that persisted for 1 hour.
However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in
both variables in group b (end-systolic elastance, 74% +/- 5% and 59% +/- 6%,
respectively, and preload-recruitable stroke work, 77% +/- 4% and 64% +/- 3%,
respectively, compared with baseline), and in group a, the values returned to
baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15
minutes after induction of brain damage and remained significantly (p < 0.05)
higher for 4 hours versus no significant change in group a. Plasma levels of
epinephrine and norepinephrine were similar in the groups before and after brain
damage. Electron microscopic study showed severe ultrastructural changes in group
b and significantly milder changes in group a. CONCLUSIONS: We conclude that
MgSO4 may protect the neonatal myocardium when administered immediately after
brain damage.
PMID- 9647091
TI - Truncal valve repair: initial experience in neonates.
AB - BACKGROUND: The identification of moderate to severe preoperative truncal valve
regurgitation has been synonymous with significant postoperative mortality after
neonatal repair of truncus arteriosus. Spurned by the deficiencies of current
truncal valve substitutes surgeons are once again reexamining the option of
truncal valve reparative techniques. METHODS: From May 1996 until June 1997, 8
children underwent correction of truncus arteriosus. A retrospective analysis was
conducted. RESULTS: There was one in-hospital death secondary to a postoperative
massive coronary air embolism. Moderate-to-severe truncal valve regurgitation was
identified clinically and confirmed with cardiac ultrasound in 3 neonates with a
mean age of 7 days (range, 4 to 12 days) all with quadracusp truncal valves.
Successful truncal valve repair was accomplished in 2 infants, with a third
neonate requiring homograft replacement with coronary reimplantation for failure
in achieving valvular competence after attempted valvuloplasty. Postoperative
echocardiograms in those neonates who underwent truncal valve repair confirmed a
functional "tricuspid" valve with only mild to mild-plus regurgitation.
CONCLUSIONS: We give further credence to the hypothesis that primary neonatal
truncal valve repair is feasible and may be successful in the avoidance and delay
of serial truncal valve replacements using either mechanical or allograft
substitutes.
PMID- 9647092
TI - Superior hydrodynamics of a modified cavopulmonary connection for the Norwood
operation.
AB - BACKGROUND: In the Fontan circulation, energy consumption at the cavopulmonary
connection is crucial. Our hypothesis was that a modification of the standard
Norwood variant of cavopulmonary connection with an extended anastomosis would
improve hydrodynamics. METHODS: The in vitro hydrodynamics of two different
Perspex glass models resembling the Norwood variant of cavopulmonary connection
(model I) and the modification (model II) were analyzed in a mock circulation at
nonpulsatile flows of 2 to 5 L/min to simulate rest and exercise. The pulmonary
flow split was varied to imitate varying lung resistances. Inferior-to-superior
caval flow ratio and size of models were increased to simulate growth. RESULTS:
The pulmonary flow was preferentially directed to the left lung in model I and
was better balanced in model II. Power losses increased exponentially with total
flow in both models and were markedly higher in model I. These differences were
attenuated in the larger models. Anastomotic turbulences were larger in model I.
Power losses in both models were relatively insensitive to changes in pulmonary
flow split. CONCLUSIONS: The proposed modification of the Norwood variant of
cavopulmonary connection seems to be hydrodynamically advantageous and warrants
further evaluation.
PMID- 9647093
TI - Growth of the subclavian artery and the anastomosis in Blalock-Taussig shunt:
absorbable versus nonabsorbable suture.
AB - BACKGROUND: We evaluated the growth of Blalock-Taussig shunts placed with
absorbable suture by cineangiographic findings and long-term results and compared
them with those in an earlier group of patients in whom we used nonabsorbable
suture. METHODS: Eighty-one patients had postoperative cineangiography 1 year or
more after a Blalock-Taussig shunt procedure. From September 1985 to December
1994, 40 patients (group I) underwent a Blalock-Taussig shunt procedure with the
use of absorbable polydioxanone suture, and from January 1980 to August 1989, 41
(group II) underwent the same operation with nonabsorbable polypropylene suture.
Cineangiograms were reviewed to assess shunt patency and growth of the subclavian
arteries and the subclavian artery-pulmonary artery anastomoses. RESULTS: At the
Blalock-Taussig shunt operation, mean outer diameters of the subclavian artery
and the anastomosis in group I were 3.8 +/- 0.1 mm and 4.1 +/- 0.1 mm,
respectively and 3.9 +/- 0.1 mm and 4.0 +/- 0.1 mm in group II. The mean inner
diameters of the subclavian artery and the anastomosis measured in postoperative
cineangiograms were 7.9 +/- 0.5 mm and 4.6 +/- 0.2 mm, respectively in group I
and 6.6 +/- 0.4 mm and 3.1 +/- 0.2 mm in group II. The diameters of both the
subclavian artery (p < 0.05) and the anastomosis (p < 0.001) were significantly
greater in group I than in group II. Five years after operation, 71.1% +/- 7.4%
of patients in group I and 54.8% +/- 8.0% in group II had good palliation.
CONCLUSIONS: The use of absorbable polydioxanone suture has an advantage in terms
of growth of the diameters of the subclavian artery and the anastomosis in a
Blalock-Taussig shunt and may improve the long-term results after this shunt
operation in infancy.
PMID- 9647094
TI - Coarctation repair: modification of end-to-end anastomosis with subclavian flap
angioplasty.
AB - BACKGROUND: Subclavian angioplasty and resection and end-to-end anastomosis for
coarctation repair carry a substantial risk of recurrence of coarctation. The
combined technique using both these methods has shown good results but requires a
longer period of continuous cross-clamping of the aorta. METHODS: A modified
technique using intermittent cross-clamping with a period of reperfusion between
cross-clamping periods was used. After the end-to-end anastomosis the clamps are
released for 10 minutes and reapplied to do the subclavian angioplasty. Between
1991 and 1996 this was done in 26 infants (mean age, 5 weeks; range, 1 day to 6
months; median, 3 weeks). Mean weight was 3.85 kg (range, 1.5 to 8.4 kg). Mean
length of follow-up was 23 months. Twenty-two patients (85%) had associated
anomalies, excluding patent ductus arteriosus, and 5 patients (19%) had another
procedure performed at the same time. RESULTS: There was no mortality. The mean
echocardiographic gradient was 4 mm Hg in the immediate postoperative period and
2.9 mm Hg during follow-up. Residual or recurrent coarctation as detected by
significant echocardiography or blood pressure gradient did not develop in any
infant. CONCLUSIONS: This modified technique of anastomosis is an effective way
of relieving coarctation with excellent intermediate-term results.
PMID- 9647095
TI - Tricuspid annuloplasty and ventricular plication for Ebstein's malformation.
AB - BACKGROUND: Seven patients with the diagnosis of Ebstein's malformation of the
tricuspid valve were operated on. Mean age was 12 years (range, 7 to 16 years).
All were cyanotic, with severe tricuspid regurgitation. Thromboembolism was not
present. No associated cardiac malformations were present. METHODS: Surgical
repair included tricuspid annuloplasty associated with longitudinal plication of
the atrialized portion of the right ventricle. This was attained by approximating
the anterior-posterior commissure with either the posterior-septal commissure or
the septal leaflet remnant. The thin atrialized ventricular wall thus excluded
remained as a cul du sac and was plicated by suturing along the longitudinal axis
of the heart. When present, the dysplastic posterior leaflet was included in the
plication. In essence, a monocuspid right atrioventricular valve was fashioned
out of the anterior leaflet. The remaining septal leaflet played a minimal
functional role. No additional procedures for treatment of arrhythmia were
associated with the technique described. RESULTS: The postoperative course was
uneventful in all patients. Mean follow-up is 4.3 years (range, 1 to 10 years).
Doppler echocardiographic studies reveal satisfactory monocusp valve function in
all patients, with adequate coaptation of the anterior leaflet and the septal
structures. CONCLUSIONS: This technique seems applicable to most forms of
Ebstein's malformation and is reproducible. The technique relies on the adequate
mobilization of the anterior leaflet. Occasionally it is necessary to free
fibrous adhesions of the leaflet to the underlying ventricular surface.
PMID- 9647096
TI - Late results and reintervention after aortic valvotomy for critical aortic
stenosis in neonates and infants.
AB - BACKGROUND: Many centers have adopted balloon valvuloplasty for treatment of
infants with critical aortic stenosis because of historically poor early results
and a lack of long-term results with surgical valvotomy. We evaluated our results
with open aortic valvotomy over the past decade, specifically examining factors
influencing survival and reintervention in the current era. METHODS: From 1986 to
1996, 37 infants in the first 3 months of life underwent open aortic valvotomy
for critical aortic stenosis. All patients underwent cardiopulmonary bypass,
valvotomy, and valve debridement under direct vision with standard techniques.
RESULTS: Early mortality was 11% (4 of 37, 70% confidence limit 7% to 20%) and
all early deaths were in neonates less than 2 weeks of age. Late death occurred
in 6 patients a mean of 10 +/- 12 months (range, 2 to 36 months) after valvotomy.
Actuarial survival, including operative deaths was 92% +/- 6% at 1 month, 78% +/-
9% at 1 year, and 73.4% +/- 10% at 10 years. In a multifactorial regression
analysis, the best predictors of death were the presence of endocardial
fibroelastosis and small body surface area and the best predictor of the need for
late reintervention was preoperative aortic annular size. Thirteen patients
required reintervention: repeat operation in 7 patients, balloon valvuloplasty in
3 patients, and both balloon valvuloplasty and reoperation in 3 patients.
Actuarial freedom from reintervention postoperatively is 97% +/- 3% at 1 month,
73% +/- 9% at 1 year, and 55% +/- 11% at 10 years. Reintervention was for
recurrent left ventricular outflow obstruction in 9 patients and mixed aortic
stenosis and aortic insufficiency in 4. Echocardiography 4.3 +/- 2.5 years after
aortic valvotomy in survivors who have not required reintervention (n = 20)
revealed a Doppler peak instantaneous systolic gradient of 37 +/- 14 mm Hg and
mild or less aortic regurgitation in 16 patients and moderate aortic
regurgitation in 4 patients. CONCLUSIONS: Current surgical results with critical
aortic stenosis in the neonate and young infant are acceptable in terms of both
late survival, reintervention, and functional results in the majority of
patients. Newer interventions, such as balloon valvuloplasty, should be carefully
evaluated for long-term results and should be compared more appropriately to
current surgical results to determine the best treatment modality for the neonate
and infant with critical aortic stenosis.
PMID- 9647097
TI - Temporary aorto-pulmonary shunt for pulmonary hypertension after truncus
arteriosus repair.
AB - We describe successful management of pulmonary hypertension with a reversible
aorto-pulmonary (central) shunt and inhaled nitric oxide gas after truncus
arteriosus repair. A temporary central shunt may provide a lifeline in those
cases refractory to pharmacologic pulmonary vasodilation as long as marginal
systemic oxygenation can be maintained.
PMID- 9647098
TI - Right atrial isolation for atrial fibrillation associated with atrial septal
defect.
AB - Two patients with atrial fibrillation associated with an atrial septal defect
underwent simultaneous surgical correction of the atrial septal defect and right
atrial isolation. The right atrium was surgically isolated while the continuity
with the sinoatrial node was preserved in the remainder of the heart. After the
operation, the patients maintained normal sinus rhythm for 99 and 65 months.
Thus, right atrial isolation offers an alternative to the current surgical
treatment for atrial fibrillation associated with an atrial septal defect.
PMID- 9647099
TI - Biatrial myxoma: a rare cardiac tumor.
AB - A previously healthy 48-year-old man presented to the hospital with a transient
ischemic attack. Echocardiography revealed a large left atrial tumor with a
second tumor in the right atrium. Surgical excision revealed a large left atrial
myxoma with extension through the interatrial septum into the right atrium.
PMID- 9647100
TI - Surgical management of tricuspid atresia and anomalous left brachiocephalic vein.
AB - An anomalous left brachiocephalic vein is an uncommon systemic venous anomaly,
which usually has no clinical significance. We describe a case of tricuspid
atresia with such an anomalous left brachiocephalic vein. The presence of this
unusual venous anomaly had a number of implications in the surgical management of
the tricuspid atresia.
PMID- 9647101
TI - Lung herniation secondary to minimally invasive direct coronary artery bypass
grafting.
AB - Lung herniation after thoracotomy is rare. We report a 66-year-old man who
presented with this complication after undergoing attempted minimally invasive
direct coronary artery bypass grafting. The defect was repaired with a composite
of Marlex mesh and methyl methacrylate.
PMID- 9647102
TI - Minimally invasive bilateral internal mammary artery bypass grafting.
AB - We report about a 71-year-old man with coronary artery double-vessel disease who
received minimally invasive coronary artery bypass grafting through a 9-cm left
lateral chest incision in the third intercostal space. Both mammary arteries were
harvested either directly (left internal mammary artery) or thoracoscopically
(right internal mammary artery) and anastomosed to the left anterior descending
artery and the circumflex artery through this single left lateral chest incision.
The postoperative course was uneventful, and the patient was discharged on
postoperative day 5.
PMID- 9647103
TI - Large eventration of diaphragm in an elderly patient treated with emergency
plication.
AB - Total eventration of the hemidiaphragm is a rare condition in adults. We report a
75-year-old woman with large eventration of the right diaphragm who required an
emergency plication because of acute progressive respiratory distress. The
symptom disappeared immediately after operation. Even in asymptomatic elderly
patients with eventration, close follow-up is recommended.
PMID- 9647104
TI - A pedunculated intraluminal foregut reduplication cyst of the proximal esophagus.
AB - A 66-year-old woman with a 3-month history of progressive dysphagia underwent
transoral excision of a pedunculated cyst arising in the proximal esophagus.
Histologic examination confirmed a pedunculated intraluminal foregut
reduplication cyst. She remains well 1 year after excision with no recurrence of
dysphagia.
PMID- 9647105
TI - Extubation of the patient after a difficult intubation.
AB - A case of a difficult intubation in a heavy smoker requiring reoperative coronary
artery bypass grafting is presented. A technique is described to extubate
patients with marginal pulmonary function and a difficult intubation using airway
exchange catheters.
PMID- 9647106
TI - Repair of aortico-left ventricular tunnel originating from the left aortic sinus.
AB - We report on a case of an 11-year-old asymptomatic child with aortico-left
ventricular tunnel arising from the left aortic sinus. Preoperative
transesophageal echocardiography showed a dilated aortic root with mild aortic
valve incompetence and demonstrated the course of the tunnel, which originated
from the left coronary sinus entering the outlet portion of the left ventricular
outflow tract. Patch closure of the aortic end of the tunnel eliminated left
ventricular volume overload with immediate marked reduction of cardiomegaly. At
10-month follow-up the child is asymptomatic and receiving no oral medications.
Control two-dimensional Doppler echocardiography shows trivial central aortic
valve incompetence.
PMID- 9647107
TI - Anastomosis of the left juxtaposed atrial appendages in a patient with tricuspid
atresia.
AB - A 9-month-old boy with left juxtaposition of the atrial appendages, tricuspid
atresia, pulmonary atresia, and ventriculoarterial discordance underwent
anastomosis between the atrial appendages after failure of balloon/blade atrial
septostomy because of restrictive atrial septal defect. For surgical creation of
atrial communication in patients with juxtaposed atrial appendages, anastomosis
between the atrial appendages seemed to be safer, more effective, and less
invasive than septectomy by Blalock-Hanlon technique or inflow occlusion
technique.
PMID- 9647108
TI - Surgical treatment of lipomatous hypertrophy of the interatrial septum.
AB - We report a case of lipomatous hypertrophy of the interatrial septum in a patient
with a recent syncopal episode and shortness of breath. Preoperative
transesophageal echocardiography demonstrated a large tumor protruding from the
interatrial septum. In addition, the patient was found to have significant
coronary artery disease and a right internal carotid artery stenosis. The patient
underwent successful resection of the mass with septal reconstruction,
aortocoronary bypass, and right carotid endarterectomy. Histology of the mass was
consistent with lipomatous hypertrophy.
PMID- 9647109
TI - Needle embolus causing cardiac puncture and chronic constrictive pericarditis.
AB - We present a case in which a needle broke off during intravenous injection and
embolized to the right heart. After cardiac perforation, the needle entered the
pericardial space and ultimately caused chronic constrictive pericarditis, which
presented as congestive heart failure. Pericardectomy and removal of the foreign
body via a median sternotomy were successful. Early surgical removal of
contaminated intrapericardial foreign bodies remains a safe and effective
approach to preventing such complications.
PMID- 9647110
TI - Repair of mitral valve and subaortic mycotic aneurysm in a child with
endocarditis.
AB - Endocarditis requiring surgical intervention in children is uncommon.
Individualized operative therapy must be fashioned to the particular pathology of
each case. In this case we describe mitral anterior leaflet homograft patch
augmentation valvuloplasty, subaortic homograft patch closure of a large mycotic
aneurysm, and homograft aortic root replacement in a 3-year-old patient with
endocarditis after remote repair of complete atrioventricular canal.
PMID- 9647111
TI - The large window ductus: a surgical trap.
AB - A rare window type of patent ductus arteriosus is reported that was large (15 mm
in maximal transverse dimension) but had virtually no length and hence was
externally invisible. The smaller aortic isthmus (4 mm in diameter), which was
intrapericardial, was mistaken for the ductus and was inadvertently clip
occluded, leading to death. After a specific diagnosis is made, the large window
ductus should be patched on cardiopulmonary bypass with a transpulmonary
approach.
PMID- 9647112
TI - Fungal purulent constrictive pericarditis in a heart transplant patient.
AB - Purulent pericarditis caused by Candida species is rare and is associated with
very high mortality. Immunosuppressed transplant patients are particularly
susceptible to fungal infections. We report a case of Candida purulent
constrictive pericarditis in an immunocompromised heart transplant patient who
was treated successfully with antifungal agents, surgical drainage, and
pericardiectomy.
PMID- 9647113
TI - A surgical method for selecting appropriate size of graft in aortic root
remodeling.
AB - We describe a surgical technique for selecting the appropriate size of a tube
graft in aortic root remodeling procedures. As the technique has a geometric
basis, we believe that our method is more accurate in determining the graft size
than others.
PMID- 9647114
TI - Proximal aortic control in traumatic rupture of the thoracic aorta.
PMID- 9647115
TI - Performance of a safe proximal anastomosis in aortic dissection.
AB - Because of the increased fragility of a freshly dissected aorta, the anastomosis
between the aortic root and a tubular prosthesis is not forgiving of technical
imperfections and may lead to troublesome bleeding. Providing an appropriate
everting surface of contact and a homogeneous distribution of tension between the
graft and aorta, as described here, should help obtain a hemostatic suture line.
PMID- 9647116
TI - Cartilage folding method for main bronchial stapling.
AB - Bronchopleural fistula is one of the most severe complications of lung
operations. To prevent bronchopleural fistula, we modified the stapling technique
to include folding of both sides of the cartilaginous main bronchus. This reduces
the tension at the center of the membranous portion of the airway. From 1991 to
1994, this technique was performed in 7 patients. Despite the fact that 4 of
these patients received adjuvant therapy, none had development of a
bronchopleural fistula.
PMID- 9647117
TI - Use of an ultrasonic scalpel as an alternative to electrocautery in patients with
pacemakers.
AB - We report the safe and effective use of an ultrasonically activated scalpel as an
alternative to unipolar electrocautery during surgical procedures in 4 patients
with pacemakers. This scalpel provided adequate hemostasis without the adverse
consequences of electromagnetic interference. As the scalpel was able to easily
cut through the silicone connector sleeve of one generator, it is not recommended
for routine generator replacement because it may damage existing pacing leads.
However, its use during nonpacemaker operations in patients with pacemakers
should be considered.
PMID- 9647118
TI - The "annular sandwich": a simple method of reinforcing a friable mitral valve
annulus.
AB - In 6 patients undergoing prosthetic mitral valve replacement a ring of Teflon
felt, instead of conventional Teflon pledgets, was used because of concern about
seating a new prosthesis in a disrupted friable mitral valve annulus. The
technique avoided the potential risk of pledget loss in the event of suture
breakage and, in these patients, prevented postoperative paraprosthetic mitral
valve regurgitation.
PMID- 9647119
TI - A method for perfusion of the leg during cardiopulmonary bypass via femoral
cannulation.
AB - Minimally invasive approaches for cardiac operations currently are gaining
increasing attention. Some of these approaches require cannulation of the femoral
vessels for cardiopulmonary bypass. A potential complication of femoral
cannulation is ischemic injury to the lower extremity in some cases that require
long bypass times. To minimize this risk we have begun cannulating the common
femoral artery distally, as well as proximally. This technique perfuses the leg
for the duration of cardiopulmonary bypass, and it can be accomplished with
minimal increases in cost and operative time.
PMID- 9647120
TI - The birth of intracardiac surgery: a semicentennial tribute (June 10, 1948-1998)
AB - On June 10, 1948, Charles Philamore Bailey, of Philadelphia, auspiciously
performed the first anatomically conceived and digitally guided operation inside
the heart: the first successful intracardiac operation. The patient, Claire Ward,
was a 24-year-old woman afflicted with severe mitral stenosis. Dwight E. Harken
and Russell C. Brock performed their own mitral operations very soon after
Bailey, using new variations of methods that had been discarded about two decades
earlier; they soon adopted the logical anatomic approach. This threesome, with
the added contributions of Robert P. Glover--Bailey's partner at the time, in the
role of respected and convincing teacher--opened the floodgates upon a decade of
so-called closed heart surgery. These accomplishments, added to the earlier
successes with the patent ductus, aortic coarctation, and "blue babies,"
justified and strengthened the demand for precise diagnosis in cardiology--at
that time a languishing specialty--and brought to the fore the indisputable
requirement to operate inside the heart with maximal control. This essay calls
attention to the semicentennial of that seminal event and reviews the origins of
surgery for mitral stenosis.
PMID- 9647121
TI - Positron emission tomography in lung cancer.
AB - Reports on positron emission tomography have become more common in the oncology
literature. After a short introduction to positron emission tomography, this
review will look at the data relating to the use of this technology in the
diagnosis, the staging, and the post-treatment evaluation of patients with lung
cancer and will discuss its potential role in these evaluations.
PMID- 9647122
TI - As originally published in 1990: Experimental study of a new porous tracheal
prosthesis. Updated in 1998.
PMID- 9647123
TI - The surgical meeting as infomercial.
PMID- 9647124
TI - Mitral valve myxoma.
PMID- 9647125
TI - Coronary artery bypass grafting: three-day discharge.
PMID- 9647126
TI - Inflammatory aneurysm or Takayasu's disease?
PMID- 9647127
TI - Homograft and SVC syndrome.
PMID- 9647128
TI - Tracheobronchial laceration after double-lumen intubation for thoracic
procedures.
PMID- 9647129
TI - Removal of Swan-Ganz catheter via a small right anterior mediastinotomy.
PMID- 9647130
TI - Mitral valve reconstruction.
PMID- 9647131
TI - Total preservation of subvalvular apparatus during mitral valve replacement.
PMID- 9647132
TI - Ultrasound detection of diaphragmatic paralysis after cardiac operations.
PMID- 9647133
TI - Reduced complication rate in bilateral mammary artery-to-coronary artery bypass
grafting.
PMID- 9647134
TI - Trasylol Pediatric Investigational Meeting. Introduction.
PMID- 9647135
TI - The Bayer 022 compassionate-use pediatric study.
AB - BACKGROUND: As part of a compassionate-use study, a placebo-controlled study was
undertaken to assess the efficacy of aprotinin in patients undergoing any
procedure associated with cardiopulmonary bypass and at increased risk of
perioperative bleeding. This article reviews results in 116 patients 16 years of
age or less. METHODS: Patients were randomly assigned to four treatment groups:
high dose, low dose, pump prime only, and placebo. Efficacy was measured by four
parameters: requirement for units of donor blood, requirement for units of donor
blood and blood product, thoracic drainage volumes, and rates of reoperation
required primarily because of diffuse bleeding. Results were separately analyzed
in all patients, patients undergoing primary procedures, patients undergoing
repeat procedures, neonates and infants 1 year of age or less, and patients older
than 1 year of age. RESULTS: There was a trend toward reduced blood and blood
product requirements with aprotinin use, least evident in neonates and infants
and particularly evident in patients undergoing repeat procedures. Aprotinin did
not reduce drainage volumes in this pediatric population. CONCLUSIONS: There is a
trend toward benefit with aprotinin use in a pediatric population, as measured by
requirement for blood and blood product, in patients who are more than 1 year of
age and in patients undergoing a repeat operation rather than a primary
sternotomy operation.
PMID- 9647136
TI - Effects of cardiopulmonary bypass and use of modified ultrafiltration.
AB - BACKGROUND: Hemodilution is a prominent problem in cardiopulmonary bypass in a
pediatric population. Ultrafiltration is a method used to reduce fluid volume and
tissue edema and to increase hematocrit without the need for blood products.
Modified ultrafiltration may offer advantages in comparison with conventional
ultrafiltration. METHODS: This article reviews the technique of modified
ultrafiltration and its use, results, complications, and safety in pediatric
cardiopulmonary bypass. RESULTS: Modified ultrafiltration in pediatric
cardiopulmonary bypass reduces total body water and serum levels of inflammatory
mediators. It results in an elevated hematocrit without the need for transfusion,
improved pulmonary compliance in the immediate postbypass period, and probably
improved cerebral metabolic recovery after deep hypothermic circulatory arrest.
CONCLUSIONS: Modified ultrafiltration can be performed safely in neonatal
patients after cardiopulmonary bypass and offers advantages in comparison with
conventional ultrafiltration.
PMID- 9647137
TI - Review of efficacy parameters.
AB - BACKGROUND: The deleterious effects of cardiopulmonary bypass are greater in
pediatric patients than in adults. The use of aprotinin to manipulate hemostasis
has become an important factor in attempts to reduce adverse consequences of
these effects. METHODS: This article reviews the literature on the use of
aprotinin in pediatric cardiac surgery. RESULTS: Available studies have many
deficiencies, often including lack of placebo control, nonhomogeneous populations
and procedures, and absence of information on aprotinin plasma concentrations.
Comparison of trial results is further complicated by differences in dose
regimens, heparin-protamine protocols, and priming. CONCLUSIONS: Further trials
are required to adequately assess aprotinin effect on platelet preservation,
particularly in neonates, to evaluate aprotinin's antiinflammatory action, and to
determine optimum dosages to achieve specific objectives. Aprotinin in pediatric
cardiac surgery has been found to be associated with no adverse effects, to
decrease fibrinolytic and probably platelet activation, and to offer important
clinical benefits in specific groups of patients.
PMID- 9647138
TI - Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin
dosage.
AB - BACKGROUND: Cardiopulmonary bypass results in inappropriate activation of the
coagulation and fibrinolytic systems. Factors such as a greater degree of
hemodilution, use of deep hypothermic circulatory arrest, the impact of cyanosis
on coagulation, and the immature coagulation system of the newborn will increase
the risk of problematic perioperative bleeding. METHODS: This article describes
the characteristics of the hemostatic system in children undergoing cardiac
operations and addresses the effect of aprotinin on hemostasis. Hemostatic
parameters were measured in 96 pediatric patients using three different doses of
aprotinin. The high-dose group (group 1) received 30,000 KIU/kg (4.2 mg/kg) of
aprotinin after induction of anesthesia and an additional bolus of 30,000 KIU/kg
(4.2 mg/kg) into the pump prime. In the low-dose group (group 2), both the
initial bolus and the pump-prime dose of aprotinin were halved to 15,000 KIU/kg
(2.1 mg/kg). Group 3 received the high dose with an additional bolus of aprotinin
to the pump prime. RESULTS: Plasma levels of aprotinin in both groups 1 and 2
were lower than the 200 KIU/mL (0.03 mg/mL) value usually reached in adults with
high-dose aprotinin treatment. Group 3 patients had levels greater than 200
KIU/mL (0.03 mg/mL) throughout the procedure. Biochemical indices of fibrinolysis
(fibrin[ogen] degradation products, D-dimers) revealed significant and dose
dependent inhibition at all three aprotinin concentrations. In contrast,
significant changes in coagulation activation markers (prothrombin fragments
F1.2, thrombin-antithrombin III complex, and fibrin monomers) were found only in
group 3. CONCLUSIONS: The inverse relationship between a small patient's blood
volume and the large pump-prime volume requires additional aprotinin to be added
to the prime to achieve plasma levels sufficient to inhibit activation of the
coagulation cascade.
PMID- 9647139
TI - Pharmacoeconomics analysis in a pediatric population.
AB - BACKGROUND: Pharmacoeconomics is becoming increasingly important in the health
care environment, but pharmacoeconomic studies are fraught with problems.
Pharmacoeconomics can be applied to analysis of the benefits of pharmacologic
hemostasis. METHODS: This article reviews the available methods of
pharmacoeconomic analysis and their inherent methodologic concerns. It reviews
pharmacoeconomic studies of pharmacologic hemostasis, with particular focus on
the Pediatric Reoperative Open Heart Surgery study. In this study, patients were
randomized to receive either high-dose aprotinin, low-dose aprotinin, or placebo.
Results were analyzed from the viewpoint of cost-benefit, cost-effectiveness
calculated with use of a roll-back decision tree, and cost-effective ratios.
RESULTS: Cost-benefit analysis showed low-dose aprotinin to have a greater cost
benefit than high-dose aprotinin, cost-effectiveness analysis and analysis of
cost-effective ratios showed high-dose aprotinin to be more cost-effective than
low-dose aprotinin, and all analyses showed aprotinin to be preferable to
placebo. CONCLUSIONS: Aprotinin in pediatric repeat open heart operations not
only has a cost-benefit but is cost-effective as well.
PMID- 9647140
TI - Endothelial-related coagulation in pediatric surgery.
AB - BACKGROUND: The endothelium plays a pivotal role in the regulation of
anticoagulant and procoagulant pathways and imbalance can produce disturbances in
coagulation. Serine protease inhibitors are also important controllers of the
coagulation system. Aprotinin can reduce postoperative bleeding, although the
mechanism of action is not clearly defined. This article focuses on a study in
children with congenital heart disease scheduled for cardiac operations to
determine the influence of aprotinin on plasmatic or endothelial-related natural
inhibitors. METHODS: Thirty children were randomly allocated either to an
aprotinin-treated group or to a control group. Levels of thrombomodulin, protein
C, free protein S, and thrombin/antithrombin complex were measured before,
during, and after cardiopulmonary bypass until the first postoperative day.
RESULTS: Levels of antithrombin III, protein C and protein S, and fibrinogen,
platelet count, and activated partial thromboplastin time were without
differences between the two groups. Thrombin/antithrombin plasma concentrations
increased significantly during cardiopulmonary bypass, without showing any
differences between aprotinin-treated and nontreated children. Thrombomodulin
plasma concentrations during cardiopulmonary bypass and until 5 hours after
cardiopulmonary bypass were significantly lower in the aprotinin-treated children
than in the control group. By the first postoperative day, the levels in the
aprotinin-treated patients had returned to baseline. CONCLUSIONS: The results
suggest a direct or indirect effect of aprotinin on endothelial cell
thrombomodulin expression and release in a soluble form into the circulation.
Whether the lower plasma concentrations with aprotinin are related to suppression
of proinflammatory mediators and preservation of endothelial cell function or
whether aprotinin has a direct action on thrombomodulin expression by the
endothelium can only be speculated.
PMID- 9647141
TI - Incidence of hypersensitivity reactions.
AB - BACKGROUND: Aprotinin is a naturally occurring serine protease inhibitor derived
from bovine lung. In common with all foreign proteins, it possesses antigenic
properties and has the possibility of allergic reactions on reexposure. METHODS:
Data are presented on the incidence of adverse reactions to aprotinin and the
time course of antibody development after initial exposure. Recommendations for
reducing the risk and sequelae of these adverse reactions are emphasized and case
reports are reviewed. RESULTS: The incidence rates of aprotinin-related reactions
to date (May 1997) at the German Heart Center are 2.7% in the adult population in
reexposures (5/183) and 1.2% in the pediatric population (3/254), with an overall
incidence of 1.8% (8/437). CONCLUSIONS: With the recommended precautions,
reexposure to aprotinin in patients with a high risk of bleeding is justified,
and the benefits of aprotinin treatment outweigh the relative risk of a serious
allergic reaction.
PMID- 9647142
TI - Neurologic sequelae associated with deep hypothermic circulatory arrest.
AB - BACKGROUND: Earlier studies of the incidence of neurologic disturbances after
deep hypothermic circulatory arrest produced conflicting results. This article
reviews the results of the Boston Circulatory Arrest Study, and another study
undertaken to compare neurologic outcome in infants after deep hypothermic
circulatory arrest using alpha-stat and pH-stat strategies. METHODS: The study
population in the Boston Circulatory Arrest Study consisted of 171 infants less
than 3 months of age. Neurologic outcomes were evaluated perioperatively, at 1
year, and at 4 years. The study population in the alpha-stat versus pH-stat study
consisted of 182 infants no older than 9 months of age. Patients were evaluated
for postoperative electroencephalographic (EEG) and clinical seizures, recovery
time to first EEG activity, and postoperative mortality and morbidity. RESULTS:
After about 30 minutes of circulatory arrest there was increasing probability of
perioperative clinical seizures, EEG seizures, and increased time to recovery of
EEG activity. One-year evaluations showed a significant relation of duration of
circulatory arrest to lowered psychomotor developmental index and increased
neurologic abnormalities. Four-year evaluations showed no difference between low
flow and circulatory-arrest patients in results of neurologic examination or in
full-scale general IQ, although there was an effect of circulatory arrest
duration on various subscores of cognitive function. Compared with the pH-stat
strategy, the alpha-stat strategy tended to be associated with more EEG seizures
and higher postoperative morbidity and mortality, and was significantly
associated with longer recovery time to first EEG activity. CONCLUSIONS: These
studies strongly suggest that in infants undergoing open heart operations for
complex congenital heart defects, low-flow bypass is associated with better
neurologic outcome than is circulatory arrest and that the pH-stat strategy is
associated with a better outcome than the alpha-stat strategy when circulatory
arrest is used.
PMID- 9647143
TI - Use of aprotinin in pediatric organ transplantation.
AB - BACKGROUND: Pediatric thoracic organ transplantation is associated with an
increased risk of perioperative bleeding. Many of these patients are undergoing
repeat surgical procedures and in general require cardiopulmonary bypass.
METHODS: This article reviews the efficacy and safety of the serine protease
inhibitor aprotinin in improving hemostasis in pediatric transplantation.
RESULTS: A review of the literature and investigations from Children's Hospital
of Philadelphia suggest that aprotinin is beneficial in pediatric lung
transplantation: high-risk patients do as well as low-risk patients. Aprotinin
also appears to be of benefit in redo heart transplantations, particularly in
patients who have had previous sternotomy or previous transplantation. Repeat use
of aprotinin appears to be safe and does reduce blood loss in retransplantation
patients. Use in the pump prime and a maintenance dose of aprotinin may be the
most effective protocol. At this time, however, it is uncertain whether aprotinin
is valuable in primary heart transplantation in low-risk patients. CONCLUSIONS:
Current practice at Children's Hospital of Philadelphia is to use aprotinin in
all lung and heart-lung transplantations and in all redo transplantations: lung,
heart-lung, and heart. The use of aprotinin in primary heart transplantations is
limited to patients who have had previous sternotomies or thoracotomies.
PMID- 9647144
TI - Is medical management of menorrhagia obsolete?
PMID- 9647145
TI - Prenatal screening.
PMID- 9647146
TI - Non-invasive fetal cell isolation from maternal blood.
PMID- 9647147
TI - Ovarian neoplasia and subfertility treatments.
PMID- 9647148
TI - Randomised comparative trial of the levonorgestrel intrauterine system and
norethisterone for treatment of idiopathic menorrhagia.
AB - OBJECTIVE: To compare the efficacy and acceptability of the levonorgestrel
intrauterine system and norethisterone for the treatment of idiopathic
menorrhagia. DESIGN: A randomised comparative parallel group study. SETTING:
Gynaecology outpatient clinic in a teaching hospital. PARTICIPANTS: Forty-four
women with heavy regular periods and a measured menstrual blood loss exceeding 80
ml. METHODS: Twenty-two women had a levonorgestrel intrauterine system inserted
within the first seven days of menses, and 22 women received norethisterone (5 mg
three times daily) from day 5 to day 26 of the cycle for three cycles. MAIN
OUTCOME MEASURES: The main outcome measure was the change in objectively assessed
menstrual blood loss after three months of treatment. RESULTS: When menstrual
blood loss at three months was expressed as a percentage of the control, the
levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median
reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median
reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the
women in the levonorgestrel intrauterine system group wished to continue with the
treatment, compared with only 22% of the norethisterone group. CONCLUSIONS: Both
the levonorgestrel intrauterine system and oral norethisterone in this regimen
provided an effective treatment for menorrhagia in terms of reducing menstrual
blood loss to within normal limits. The levonorgestrel intrauterine system was
associated with higher rates of satisfaction and continuation with treatment, and
thus offers an effective alternative to currently available medical and surgical
treatments for menorrhagia.
PMID- 9647149
TI - A randomised comparison of strategies for reducing infective complications of
induced abortion.
AB - OBJECTIVES: To determine lower genital tract carriage rates of C. trachomatis, N.
gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy.
To compare two clinical management strategies for minimising the risks of
infective morbidity after induced abortion. DESIGN: Prevalence of infections was
assessed by screening women undergoing abortion. Clinical management strategies
were compared by a randomised trial. SETTING: The gynaecology departments of four
hospitals in Scotland. PARTICIPANTS: 1672 women undergoing induced abortion.
INTERVENTIONS: Women randomised to prophylaxis received metronidazole 1 g
rectally before abortion plus doxycycline 100 mg twice daily for seven days.
Women randomised to screen-and-treat received appropriate antibiotics only if
screening proved positive for one or more infection. MAIN OUTCOME MEASURES:
Prevalences of infections; morbidity in the eight weeks following abortion as
assessed by reported symptoms, general practitioner consultation and prescription
rates and hospital re-attendances; costs to the NHS of alternative managements.
RESULTS: Prevalence rates: C. trachomatis 5.6%; N gonorrhoeae 0.19%; bacterial
vaginosis 17.5%. Overall, women allocated to receive prophylaxis had lower rates
of measures of short term infective morbidity than those allocated to screen-and
treat. These differences only reached statistical significance for women who were
reported negative on screening. The direct costs to the NHS of prophylaxis and
screen-and-treat were calculated to be 8.17 and 18.34 per woman, respectively.
CONCLUSIONS: Prevalences of lower genital tract infections which have been
implicated in increased rates of infective morbidity after abortion are similar
to those reported elsewhere. Universal antibiotic prophylaxis is at least as
effective as a policy of screen-and-treat in minimising the risk of short term
infective morbidity and is far more cost efficient.
PMID- 9647150
TI - Impact of surgery for stress incontinence on the social lives of women.
AB - OBJECTIVE: To assess the feasibility of collecting disease-specific and generic
data on the impact of surgery on the social lives of women with stress
incontinence; to describe the social impact of surgery in a representative group;
and to determine the effect of timing on the assessment of outcome. DESIGN:
Longitudinal study; questionnaires before and three, six, and twelve months after
surgery. SETTING: Eighteen hospitals in North Thames region. PARTICIPANTS: Four
hundred and forty-two women undergoing surgery for stress incontinence between
January 1993 and June 1994. MAIN OUTCOME MEASURES: Post-operative recovery time,
stress incontinence symptom impact index, activities of daily living, and cost of
protection. RESULTS: Post-operative recovery was uneventful for most women, but
three months after surgery 24% of those in paid employment beforehand were still
on sick or unpaid leave. Most women (75%) reported that stress incontinence had
less adverse impact on their lives three months after surgery, though 18%
reported no change, and 7% felt life was worse. The likelihood of improvement was
similar regardless of whether pre-operative urodynamic studies had been
conducted. The extent of improvement was dependent on pre-operative severity.
Similar findings were obtained six and twelve months after surgery. After an
initial slight but nonsignificant deterioration in their ability to carry out
activities of daily living, women gained a slight benefit from surgery
(proportion with no or only slight limitation rose from 72% to 82%; P=0.0001).
The mean cost of protection (pads and towels) fell from 8.59 pound sterling a
month before surgery to 2.99 pound sterling a month one year after surgery, by
which time 68% of women were not using protection. In contrast, 11% were still
spending over 10 pound sterling a month. CONCLUSIONS: It is possible to collect
standard data on the impact of surgery on social functioning and, thus, provide
women with better information on likely outcomes. The benefits of pre-operative
urodynamic investigations need to be assessed. The stability of the outcome
measures over the first post-operative year suggest that outcomes need to be
assessed only once and at any time from three to twelve months after the
operation.
PMID- 9647151
TI - A multicentre study comparing cervicography and cytology in the detection of
cervical intraepithelial neoplasia.
AB - OBJECTIVE: To evaluate in a multicentre setting the performance of cervicography
compared with cytology for the detection of cervical intraepithelial neoplasia.
DESIGN: Prospective comparative multicentre study. SETTING: Three hospitals with
outpatient gynaecology clinics and three cancer screening clinics. PARTICIPANTS
AND METHODS: Cervical cytology and cervicography were performed on 5724 women. If
one or both tests showed an abnormality suggestive of at least a low grade
squamous intraepithelial lesion, a colposcopy with directed biopsy was carried
out. Cervicograms were evaluated by four experienced 'senior' assessors and by
ten new 'junior' assessors. RESULTS: Results were fully analysed for 5192 women
(91%). A cervical biopsy was carried out on 228 women and this confirmed a true
positive lesion in 116 cases (incidence rate: 2.2%). Of these, 72 cases (62.1%)
were detected by cervicography and 64 (55.2%) by cytology. This difference was
not statistically significant (McNemar: P=0.475). Only 20 cases of CIN (17%) were
concordantly detected by both tests. Senior assessors performed significantly
better with a detection capacity of 80.6% compared to a detection capacity of
56.6% for the junior assessors (chi2 test: P=0.034). CONCLUSIONS: Cervicography
must be considered as a complementary test to cytology. Overall detection of CIN
is improved, but this is mainly due to the detection of more low grade lesions.
The lower sensitivity and specificity in high grade lesions compared with
cervical cytology is the main limitation of cervicography in screening for CIN.
An important finding was that the performance of cervicography was highly
dependent on the assessors' experience.
PMID- 9647152
TI - The rise in caesarean section rate: the same indications but a lower threshold.
AB - OBJECTIVE: To investigate the reasons for the rise in caesarean section rate and
note any change in indications. DESIGN: A retrospective, descriptive study
comparing the years 1962 and 1992. SETTING: A large city centre teaching
hospital. RESULTS: There was an overall increase in the caesarean section rate
from 6-8% in 1962 to 18.1% in 1992. No single cause contributed more than 30%
towards this increase. The main indications in both years were similar: failure
to progress (42.2% vs 36.7%) and fetal indications (18.1% vs 18.9%). The largest
relative increases were in the malpresentation group (10.8% vs 16%) and previous
caesarean section (4.5% vs 15.2%). CONCLUSIONS: These results suggest that there
has been a lowering in the overall threshold concerning the decision to carry out
a caesarean section rather than changes in obstetric management. Obstetricians
and the women in their care have to decide whether the current balance between
risk and benefit is acceptable or whether they wish to alter the underlying
philosophy if any significant reduction is to be sustained.
PMID- 9647153
TI - Effective analgesia following perineal injury during childbirth: a placebo
controlled trial of prophylactic rectal diclofenac.
AB - OBJECTIVE: To determine if diclofenac suppositories administered prophylactically
produce effective and lasting analgesia following perineal injury. DESIGN: A
randomised double blind placebo controlled trial. SETTING: York District
Hospital. POPULATION: One hundred women sustaining objective perineal injury
(second degree tear or episiotomy) during spontaneous vaginal delivery at term.
METHODS: Suppositories were administered at the time of repair and approximately
12 hours later. The suppositories were randomised prior to issue by the pharmacy
department and contained either 100 mg diclofenac or placebo. MAIN OUTCOME
MEASURES: Pain scores assessed at 12, 24, 48 and 72 hours after delivery using a
six point numerical scoring system and the use of additional analgesia and local
treatments to the perineum. RESULTS: The mean pain score was significantly
reduced in the diclofenac group at 24, 48 and 72 hours after delivery (0.86, 0.7
and 0.59, respectively) compared with the control group (1.64, 1.31 and 1.5; P <
0.005). In addition there was less supplementary analgesia required (eight women
only at 72 hours compared with 15 in the control group) and this was limited to
paracetamol or topical treatments to the perineum. CONCLUSION: Prophylactic
rectal diclofenac provides effective analgesia after perineal repair and its
effect appears to be maintained into the second and third postpartum days.
PMID- 9647154
TI - Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre
eclamptic pregnancies.
AB - OBJECTIVE: To investigate whether syncytiotrophoblast microvilli (STBM) are shed
into the maternal circulation in increased amounts in pre-eclamptic pregnancies
as a possible cause of maternal vascular endothelial dysfunction. DESIGN: A time
resolved fluoroimmunoassay was developed to measure STBM levels in peripheral and
uterine venous plasma from normal pregnant and pre-eclamptic women. Three colour
flow cytometry was used to assess the microparticulate nature of the STBM in
pregnancy plasma. The effects of these plasmas on endothelial cell proliferation
was compared and a correlation with the levels of STBM detected was sought.
SETTING: A laboratory investigation using clinical samples obtained from an
obstetric practice in a teaching hospital. SAMPLES: Peripheral venous plasma from
20 women with established pre-eclampsia, 20 normal pregnant women matched for
age, gestation and parity, and 10 nonpregnant women of reproductive age. Paired
uterine and peripheral venous plasma taken at caesarean section from 10 women
with pre-eclampsia and 10 unmatched normal pregnant women. RESULTS: STBM were
detected in the plasma of pregnant women by both flow cytometry and time-resolved
fluoroimmunoassay. Significantly higher levels of STBM were found in women with
established pre-eclampsia (P=0.01). STBM concentrations were higher in uterine
venous plasma than in concurrently sampled peripheral venous plasma, confirming
their placental origin. A significant correlation was found between the amount of
STBM in the plasma and endothelial cell inhibitory activity. CONCLUSIONS: STBM
are shed into the maternal circulation (microvillous deportation) and are present
in significantly increased amounts in pre-eclamptic women. They may contribute to
the endothelial dysfunction underlying the maternal syndrome of pre-eclampsia.
PMID- 9647155
TI - A role for noradrenaline in pre-eclampsia: towards a unifying hypothesis for the
pathophysiology.
AB - OBJECTIVE: To compare plasma catecholamine (noradrenaline and adrenaline) levels
in pre-eclamptic to normotensive pregnancy, and to study the activity of
synthetic enzymes for catecholamines in placental and trophoblastic cell
cultures. We postulated that catecholamines might be an important signal secreted
by the fetoplacental unit in pre-eclampsia. METHODS: We recruited 12 women with
pre-eclampsia and 12 pregnant women with nonproteinuric hypertension undergoing
delivery by caesarean section, 23 normotensive women undergoing elective
caesarean section at term, and 26 normotensive primigravid women with ongoing
pregnancies at gestations equivalent to those women with pre-eclampsia. We
measured venous blood concentrations of catecholamines. Following delivery, we
studied tyrosine hydroxylase (the rate limiting enzyme for catecholamine
synthesis) activity in placental tissue of these women as well as from four
eclamptic women not in the observer study. We used Northern blot analysis to
quantify mRNA for tyrosine hydroxylase and dopamine-beta-hydroxylase (D-beta-H, a
non-rate-limiting synthetic enzyme for catecholamine) in placental tissue, as
well as in trophoblast cells in primary culture and trophoblast cell lines.
RESULTS: Venous blood concentrations of noradrenaline were significantly higher
in pre-eclamptic women compared with normotensive women. Tyrosine hydroxylase
activity was greater in placental tissue from pre-eclamptic and eclamptic
compared with normotensive pregnancies, as were mRNA levels for this enzyme. The
mRNA levels for the non-rate-limiting D-beta-H in women with pre-eclampsia were
similar to those in normotensive pregnancies. First trimester trophoblast cells
in primary culture and trophoblast cell lines transcript mRNA for tyrosine
hydroxylase and D-beta-H. CONCLUSIONS: Trophoblasts have the capacity to secrete
catecholamines, and we found increased activity of the rate-limiting synthetic
enzyme in placental tissue from pre-eclamptic pregnancies. We postulate that the
higher levels of catecholamines we found in the plasma of women with pre
eclampsia might be of placental origin. We hypothesise that in pre-eclampsia
ischaemic trophoblast tissue secretes catecholamines as a physiological signal to
increase maternal blood flow to the fetoplacental unit, which itself is spared
the vasoconstrictor effects of catecholamines (placental vessels are known to be
unresponsive to catecholamines). However, since the basic pathology--defective
trophoblast invasion--is not corrected, the increased blood flow fails to resolve
the ischaemia, and the secretion of catecholamines is therefore sustained or even
enhanced. Noradrenaline is known to cause lipolysis. This results in breakdown of
triglycerides to free fatty acids, which are oxidized to lipid peroxides. The
latter are cytotoxic and cause widespread endothelial cell damage and
dysfunction, culminating in the clinical syndrome of pre-eclampsia.
PMID- 9647156
TI - Placental hormones during induced hypoglycaemia in pregnant women with insulin
dependent diabetes mellitus: evidence of an active role for placenta in hormonal
counter-regulation.
AB - OBJECTIVE: To study the effect of induced hypoglycaemia on serum levels of the
placental hormones oestriol, human placental lactogen, placental growth hormone
and progesterone in the third trimester of pregnancy. DESIGN: A prospective
experimental investigation. SETTING: High risk pregnancy unit and diabetes
research unit at Karolinska Institutet Danderyd Hospital, a university hospital.
PARTICIPANTS: Ten women with insulin-dependent diabetes mellitus in the third
trimester of pregnancy. METHODS: Venous blood samples were collected every 15
minutes for analyses of oestriol, progesterone, human placental lactogen and
placental growth hormone, during the 150 min of a hyperinsulinaemic hypoglycaemic
clamp, which maintained arterial blood-glucose level of about 2.2 mmol/l. MAIN
OUTCOME MEASURES: Levels of analysed placental hormones during hypoglycaemia.
RESULTS: A statistically significant increase was observed in placental growth
hormone during hypoglycaemia (P < 0.0001), whereas the placental hormones
progesterone, human placental lactogen and oestriol did not show changes of
clinical significance. CONCLUSIONS: The increase in placental growth hormone
indicates that the placenta is an endocrine organ which may take an active part
in acute metabolic processes, such as here in the hormonal counterregulation of
hypoglycaemia.
PMID- 9647157
TI - Biochemical modifications of human whole saliva induced by pregnancy.
AB - OBJECTIVE: To assess human unstimulated whole saliva components during pregnancy,
to determine the relation, if any, between pregnancy and oral health,
particularly total protein concentration, alpha-amylase activity, sialic acid
content and calcium and phosphate concentrations were evaluated. DESIGN: Cross
sectional study. PARTICIPANTS: Forty-five healthy primigravid women; 15
nonpregnant women acted as controls. RESULTS: 1. A higher total protein content
at 10 and 21 weeks of gestation with respect to the controls and to pregnant
women at 40 weeks; 2. a higher alpha-amylase activity at 10 and 21 weeks of
gestation compared with the controls and to pregnant women at 40 weeks; 3. an
increased sialic acid content at 21 and 40 weeks; 4. decreased calcium and
phosphorus concentrations at 21 and 40 weeks of gestation. CONCLUSIONS: Pregnancy
modifies saliva composition. This could play a pivotal role in the incidence of
pregnancy-induced dental caries.
PMID- 9647158
TI - Fetal cardiac function and septal thickness in diabetic pregnancy: a controlled
observational and reproducibility study.
AB - OBJECTIVE: To determine the reproducibility of duplex Doppler waveform analysis
and fetal cardiac interventricular septal thickness measurement and to compare
these parameters in matched pregnancies with and without well-controlled maternal
Type 1 diabetes at 18-20 weeks of gestation. DESIGN: A prospective blind twin
cohort study and a blinded inter-observer and intra-observer agreement study.
SETTING: A tertiary referral prenatal diagnostic unit within a university
hospital. RESULTS: Good inter- and intra-observer agreement was found for the
measurement of transvalvular peak flow velocities and the duration of ventricular
ejection in the fetal heart. Inter-observer agreement for aortic flow
acceleration rate was poor. M-mode measurement of interventricular septal
thickness showed moderate reproducibility. The mean (SD) width of the
interventricular septum in the fetuses of well controlled diabetic women was 2 1
mm (0.2 mm), and was significantly greater (P=0.01) when compared with the
corresponding value in matched controls [1.9 mm (0.2 mm)]. No cardiac functional
differences were evident. CONCLUSIONS: On-screen video analysis of Doppler
cardiac flow waveforms and M-mode measurement of intraventricular septal
thickness demonstrated good reproducibility. The fetuses of well controlled
diabetic pregnancies demonstrated signs of altered cardiac morphology early in
pregnancy, before any evident alterations in cardiac function.
PMID- 9647159
TI - Double-blind, placebo-controlled study of magnesium hydroxide for treatment of
sensory urgency and detrusor instability: preliminary results.
AB - In a prospective, randomised, double-blind, placebo-controlled study 40 women
with sensory urgency or detrusor instability randomly received either magnesium
hydroxide (group A) or placebo (group B). Pre- and post-treatment symptoms,
frequency-volume charts and cystometry results were compared. Eleven of 20
patients receiving magnesium (55%) reported a subjective improvement of their
urinary symptoms, compared with five patients taking placebo (20%). In both study
groups there was no statistically significant difference in pre- and post
treatment urodynamic parameters in those reporting symptomatic improvement.
Magnesium was well tolerated by patients in group A, and no side effects were
reported. These results suggest that magnesium hydroxide may be beneficial for
detrusor instability or sensory urgency in women.
PMID- 9647160
TI - Expectant management of missed miscarriage.
AB - The option of expectant management was offered 221 women with ultrasound
diagnosis of missed miscarriage. Eighty-five women (38%) accepted; the remaining
136 women chose surgical evacuation of retained products of conception. In the
expectant management group 21 women (24.7%) had a complete miscarriage, 14
(16.5%) had incomplete miscarriage necessitating surgery, and 50 (58.8%)
requested surgery within 48 days from the original diagnosis. These results
suggest that the success of expectant management of missed miscarriage is too low
to justify its use in routine clinical practice.
PMID- 9647161
TI - Flexible outpatient hysteroscopy without anaesthesia: a safe, successful and well
tolerated procedure.
AB - The objective of this study was to assess the feasibility and tolerance of
diagnostic outpatient flexible hysteroscopy without anaesthesia. Records from 554
consecutive patients were analysed retrospectively. Success rate, reasons for
failure, adverse reactions and level of pain were the main outcome measures.
Hysteroscopy was successful in 90.5% of patients and well tolerated in 93.3%;
5.4% experienced moderate to severe pain. Inability to negotiate the cervical
canal accounted for 47% of failed procedures and poor view for 42%. These results
suggest that flexible outpatient hysteroscopy without anaesthesia is a successful
and well tolerated procedure.
PMID- 9647162
TI - Successful pregnancy in a patient with type III glycogen storage disease managed
with cornstarch supplements.
PMID- 9647163
TI - Ultrasound detection of vault haematoma following vaginal hysterectomy.
PMID- 9647164
TI - Complications of laparoscopy: a prospective multicentre observational study.
PMID- 9647165
TI - Long-term follow-up review of patients who underwent laminectomy for lumbar
stenosis: a prospective study.
AB - OBJECT: Decompressive laminectomy for stenosis is the most common operation
performed in the lumbar spine in older patients. This prospective study was
designed to evaluate long-term results in patients with symptomatic lumbar
stenosis. METHODS: Between January 1984 and January 1995, 170 patients underwent
surgery for lumbar stenosis (86 patients), lumbar stenosis and herniated disc (61
patients), or lateral recess stenosis (23 patients). The male/female ratio for
each group was 43:43, 39:22, and 14:9, respectively. The average age for all
groups was 61.4 years. For patients with lumbar stenosis, the success rate was
88.1 % at 6 weeks and 86.7% at 6 months. For patients with lumbar stenosis and
herniated disc, the success rate was 80% at 6 weeks and 77.6% at 6 months, with
no statistically significant difference between the two groups. For patients with
lateral recess stenosis, the success rate was 58.7% at 6 weeks and 63.6% at 6
months; however, the sample was not large enough to be statistically significant.
One year after surgery a questionnaire was sent to all patients; 163 (95.9%)
responded. The success rate in patients with stenosis had declined to 69.6%,
which was significant (p = 0.012); the rate for patients with stenosis and
herniated disc was 77.2%; and that for lateral recess stenosis was 65.2%. Another
follow-up questionnaire was sent to patients 1 to 11 years after surgery (average
5.1 years); 146 patients (85.9%) responded, 10 (5.9%) were deceased, and 14
(8.2%) were lost to follow-up review. At 1 to 11 years the success rate was 70.8%
for patients with stenosis, 66.6% for those with stenosis and herniated disc, and
63.6% for those with lateral recess stenosis. Eleven patients who underwent
reoperation were included in the group of patients whose surgeries proved
unsuccessful, regardless of their ultimate outcome. There was no statistically
significant difference in outcome between 1 year and 1 to 11 years with respect
to stenosis, stenosis with herniated disc, and lateral recess stenosis.
CONCLUSIONS: In conclusion, long-term improvement after laminectomy was
maintained in two-thirds of these patients.
PMID- 9647166
TI - Posterior atlantoaxial facet screw fixation in rheumatoid arthritis.
AB - OBJECT: This retrospective review was conducted to determine the efficacy of
transarticular screw fixation in a group of patients who were treated for
rheumatoid atlantoaxial instability. METHODS: Thirty-six patients (mean age 63
years) with rheumatoid atlantoaxial instability were treated with posterior
atlantoaxial transarticular screw fixation supplemented with an interspinous C1-2
strut graft-cable construct to provide immediate three-point fixation to
facilitate bone fusion. Previous attempts at fusions by using bone grafting with
wire fixation at other institutions had failed in six of these patients. Six
patients underwent transoral odontoid resections for removal of large irreducible
pannus as a first-stage procedure, which was followed within 2 to 3 days by the
posterior procedure. Postoperatively, 33 patients were placed in hard cervical
collars and three required halo vests because of severe osteoporosis. Of eight
patients categorized as Ranawat Class II preoperatively, all eight returned to
normal after surgery; of eight patients in Ranawat Class III-A preoperatively,
four improved to Class II and four remained unchanged. All 20 patients classified
as Ranawat Class I preoperatively recovered completely. Pain decreased or
resolved in all patients, and there were no complications related to
instrumentation. At follow-up review (mean 2 years), 33 patients (92%) had solid
bone fusions, and three (8%) had stable fibrous unions. CONCLUSIONS: Posterior
atlantoaxial transarticular screw fixation provides a good surgical alternative
for the management of patients with rheumatoid atlantoaxial instability. This
technique provides immediate three-point rigid fixation of the C1-2 region, thus
obviating the need for halo vest immobilization in most cases.
PMID- 9647167
TI - Management and results of sciatic nerve injuries: a 24-year experience.
AB - OBJECT: The purpose of this retrospective clinical study was to present results
and provide management guidelines for various types of sciatic injuries. METHODS:
Over a 24-year period, 380 patients with sciatic nerve injuries were managed. In
230 patients (60%), the injury was at the buttock level, with injection injuries
comprising more than half of these cases. Thigh-level sciatic injury was
evaluated in 150 cases (40%) and was usually secondary to one of four main
causes: 1) gunshot wound; 2) femur fracture; 3) laceration; or 4) contusion.
Patients with partial deficits uncomplicated by severe pain or with significant
spontaneous recovery or late referral were managed medically. Surgical
exploration was not indicated in 23% of injuries at the thigh level and almost
50% of those at the buttock level. Most of these patients achieved partial but
good spontaneous recovery, especially in the tibial division distribution.
Surgical intervention was required for more complete and persistent deficits in
either the tibial or peroneal distribution. Divisions of the sciatic nerve were
split apart and evaluated independently. Management was guided by nerve action
potential (NAP) recordings, which indicated whether neurolysis or resection of
the lesion was required. Repair was then made by using sutures or more frequently
by graft placement. In most cases in which neurolysis was performed because a
positive NAP was recorded distal to the lesion, useful function was found in the
peroneal distribution. Unfortunately, significant recovery occurred in only 36%
of patients who received suture or graft repairs of the peroneal division. Good
to-excellent outcome was common for the tibial division, even in cases in which
repair was proximal and required lengthy grafts. The relatively favorable
recovery of tibial as opposed to peroneal divisions of the sciatic nerve occurred
regardless of the level or mechanism of injury. CONCLUSIONS: Surgical exploration
and, when necessary, repair of sciatic nerve injuries is worthwhile in selected
cases.
PMID- 9647168
TI - Occipital plagiocephaly: a critical review of the literature.
AB - OBJECT: The literature on occipital plagiocephaly (OP) was critically reviewed to
determine the feasibility of establishing treatment recommendations. METHODS:
Using standard computerized search techniques, medical literature databases
containing peer-review articles dating from 1966 were queried for key words
related to OP. The titles of all articles were scanned for relevance, and copies
of potentially relevant articles published in English were reviewed. Articles in
which treatment was discussed were categorized according to their weight of
evidence as Class I (prospective randomized controlled trials), Class II
(clinical studies in which data are collected prospectively or retrospective
analyses based on clearly reliable data), and Class III (most studies based on
retrospectively collected data) to evaluate their contribution to developing a
consensus on the treatment of OP. Of the 4308 articles identified, all but 89
were excluded. Based on the review of these articles, the actual incidence of OP
is unknown, and no population-based studies of its incidence or prevalence exist.
The reported incidence of lambdoid craniosynostosis ranges from 3 to 20% with
differences in diagnostic criteria accounting for the variability. With the
possible exception of a lambdoid suture that is replaced by a dense ridge of
bone, no other diagnostic criteria have been agreed on. There were no Class I
studies and only one Class II study provided comparisons of outcomes in more than
one treatment group with outcomes in an untreated group. Recommended treatment
options included observation only, mechanical interventions, and a variety of
surgical techniques. CONCLUSIONS: Controlled clinical trials are needed before
any form of intervention can be recommended for the treatment of OP. If surgery,
which is expensive and potentially dangerous, is to continue to play a role in
the management of this condition, efforts should be made to determine if patients
with untreated OP have suffered from lack of treatment.
PMID- 9647169
TI - Incidence of silent hemorrhage and delayed deterioration after stereotactic brain
biopsy.
AB - OBJECT: Many neurosurgeons routinely obtain computerized tomography (CT) scans to
rule out hemorrhage in patients after stereotactic procedures. In the present
prospective study, the authors investigated the rate of silent hemorrhage and
delayed deterioration after stereotactic biopsy sampling and the role of
postbiopsy CT scanning. METHODS: A subset of patients (the last 102 of
approximately 800 patients) who underwent stereotactic brain biopsies at the
Toronto Hospital prospectively underwent routine postoperative CT scanning within
hours of the biopsy procedure. Their medical charts and CT scans were then
reviewed. A postoperative CT scan was obtained in 102 patients (aged 17-87 years)
who underwent stereotactic biopsy between June 1994 and September 1996. Sixty-one
patients (59.8%) exhibited hemorrhages, mostly intracerebral (54.9%), on the
immediate postoperative scan. Only six of these patients were clinically
suspected to have suffered a hemorrhage based on immediate postoperative
neurological deficit: in the remaining 55 (53.9%) of 102 patients, the hemorrhage
was clinically silent and unsuspected. Among the clinically silent intracerebral
hemorrhages, 22 measured less than 5 mm. 20 between 5 and 10 mm, five between 10
and 30 mm, and four between 30 and 40 mm. Of the 55 patients with clinically
silent hemorrhages, only three demonstrated a delayed neurological deficit (one
case of seizure and two cases of progressive loss of consciousness) and these all
occurred within the first 2 postoperative days. Of the neurologically well
patients in whom no hemorrhage was demonstrated on initial postoperative CT scan,
none experienced delayed deterioration. CONCLUSIONS: Clinically silent hemorrhage
after stereotactic biopsy is very common. However, the authors did not find that
knowledge of its existence ultimately affected individual patient management or
outcome. The authors, therefore, suggest that the most important role of
postoperative CT scanning is to screen for those neurologically well patients
with no hemorrhage. These patients could safely be discharged on the same day
they underwent biopsy.
PMID- 9647170
TI - Multiple schwannomas: schwannomatosis or neurofibromatosis type 2?
AB - OBJECT: The aim of this study was to clarify the clinical outcome of
schwannomatosis, a rare condition characterized by multiple nonvestibular
schwannomas in the absence of meningiomas, intraspinal ependymomas, and other
clinical signs of neurofibromatosis type 2 (NF2). METHODS: Nine patients with
schwannomatosis treated at one institution are presented and their clinical
course during a median follow-up time of 9.9 years is discussed. The patients
were typically middle-aged at the time of their first operation (median 43.5
years), none had a positive family history of schwannomatosis or NF2, and none
showed cutaneous or ocular signs of NF2. On histopathological examination the
tumors from the patients with schwannomatosis showed a lobular appearance and
frequent Verocay bodies, signs indicating NF2, more often than 20 sporadic
schwannomas that were investigated as controls. Two patients died of unrelated
causes at 3.2 and 9.9 years, respectively, of follow up. Magnetic resonance
images of the head and spine were obtained in seven patients at the end of the
follow-up period. New spinal schwannomas were detected in one patient and a
residual schwannoma in three. No germline mutations of the NF2 gene were found in
these seven patients. Two additional patients originally included in the
schwannomatosis group who were 8.6 and 11.7 years old at initial surgery had NF2.
One was diagnosed at follow-up review and the other developed a fulminant disease
that led to death in 4 years. CONCLUSIONS: The clinical course, long-term
outcome, and genetic mechanism of schwannomatosis differ from that of NF2.
PMID- 9647171
TI - Systemic T cell adoptive immunotherapy of malignant gliomas.
AB - OBJECT: To determine the feasibility, toxicity, and potential therapeutic
benefits of systemic adoptive immunotherapy, 10 patients with progressive primary
or recurrent malignant glioma received this treatment. Adoptive immunotherapy,
the transfer of immune T lymphocytes, is capable of mediating the regression of
experimental brain tumors in animal models. In animal models, lymph nodes (LNs)
that drain the tumor vaccine site are a rich source of tumor-immune T cells.
METHODS: In this clinical study, patients were inoculated intradermally with
irradiated autologous tumor cells and granulocyte macrophage-colony stimulating
factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7
days after vaccination, were stimulated sequentially with staphylococcal
enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used
to expand the stimulated cells. The maximum cell proliferation was 350-fold over
10 days of culture. The activated cells were virtually all T cells consisting of
various proportions of CD4 and CD8 cells. These cells were given to patients by
intravenous infusion at doses ranging from 9 x 10(8) to 1.5 x 10(11). There were
no Grade 3 or 4 toxicities associated with the treatment. Following T-cell
transfer therapy, radiographic regression that lasted at least 6 months was
demonstrated in two patients with recurrent tumors. One patient demonstrated
stable disease that has lasted for more than 17 months. The remaining patients
had progressive disease; however, four of the eight patients with recurrent tumor
remain alive more than 1 year after surgery for recurrence. Three patients
required intervention with corticosteroid agents or additional surgery
approximately 1 month following cell transfer. CONCLUSIONS: These intriguing
clinical observations warrant further trials to determine whether this approach
can provide therapeutic benefits and improve survival.
PMID- 9647172
TI - Current neurosurgical management and the impact of the extent of resection in the
treatment of malignant gliomas of childhood: a report of the Children's Cancer
Group trial no. CCG-945.
AB - OBJECT: One hundred seventy-two children with high-grade astrocytomas were
treated by members of the Children's Cancer Group in a prospective randomized
trial designed to evaluate the role of two chemotherapy regimens. Seventy-six
percent of the patients (131 children) in whom a diagnosis of either anaplastic
astrocytoma or glioblastoma multiforme was confirmed by central pathological
review are the subject of this report. METHODS: Patients were stratified
according to the extent of tumor resection (biopsy [< 10%], partial resection [10
50%], subtotal resection [51-90%], near-total resection [> 90%], and total
resection) as determined by surgical observation and postoperative computerized
tomography scanning. Information on contemporary neurosurgical management was
obtained from the patient's operative records and standardized neurosurgical
report forms. The vast majority of tumors were supratentorial: 63% (83 tumors) in
the superficial cerebral hemisphere, 28% (37 tumors) in the deep or midline
cerebrum, and only 8% (11 tumors) in the posterior fossa. A significant
association was detected between the primary tumor site and the extent of
resection (p < 0.0001). A radical resection (> 90%) was performed in 37% of the
children: 49% of the tumors in the superficial hemisphere and 45% of tumors in
the posterior fossa compared with 8% of midline tumors. Tumor location could also
be used to predict the need for both temporary and permanent cerebrospinal fluid
(CSF) diversion. Half of the deep tumors and 8% of the hemispheric astrocytomas
ultimately required a permanent CSF shunt. Improvement in preoperative
neurological deficits and level of consciousness was seen in 36% and 34% of the
children, respectively. New or increased deficits were present in 14% of the
children, with 6% experiencing a diminished sensorium after surgery.
Postoperative nonneurological complications were rare: infection, hematoma, and
CSF fistula each occurred in 1.7% of the children. Univariate and multivariate
analyses demonstrated that radical tumor resection (> 90%) was the only
therapeutic variable that significantly improved progression-free survival (PFS)
rates. For all patients with malignant astrocytomas, the distributions of PFS
rates were significantly different (p = 0.006) following radical resection
compared with less extensive (< or = 90%) resection. The 5-year PFS rates were 35
+/- 7% and 17 +/- 4%, respectively. The differences in the distribution of PFS
rate were significant for the subsets of patients with anaplastic astrocytoma (p
= 0.055) and glioblastoma multiforme (p = 0.046). The 5-year PFS rates for
anaplastic astrocytoma were 44 +/- 11% and 22 +/- 6% for cases in which the tumor
was radically resected and less than radically resected, respectively; whereas
the 5-year PFS rates for glioblastoma multiforme were 26 +/- 9% and 4 +/- 3% for
cases in which the tumor was radically resected and less than radically resected,
respectively. CONCLUSIONS: The demonstration of a survival advantage provided by
radical resection should prompt neurosurgeons to treat malignant pediatric
astrocytomas with aggressive surgical resection prior to initiation of
radiotherapy or adjuvant chemotherapy.
PMID- 9647173
TI - Dual-isotope single-photon emission computerized tomography scanning in patients
with glioblastoma multiforme: association with patient survival and
histopathological characteristics of tumor after high-dose radiotherapy.
AB - OBJECT: The study was conducted to determine the association between dual-isotope
single-photon emission computerized tomography (SPECT) scanning and
histopathological findings of tumor recurrence and survival in patients treated
with high-dose radiotherapy for glioblastoma multiforme. METHODS: Studies in
which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used
were performed 1 day before reoperation in 47 patients with glioblastoma
multiforme who had previously been treated by surgery and high-dose radiotherapy.
Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the
contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that
in the cerebellar cortex. Patients were stratified into groups based on the
maximum radioisotope uptake values in their tumor beds. The significance of
differences in patient gender, histological characteristics of tissue at
reoperation, and SPECT uptake group with respect to 1-year survival was
elucidated by using the chi-square statistic. Comparisons of patient ages and
time to tumor recurrence as functions of 1-year survival were made using the t
test. Survival data at 1 year were presented according to the Kaplan-Meier
method, and the significance of potential differences was evaluated using the log
rank method. The effects of different variables (tumor type, time to recurrence,
and SPECT grouping) on long-term survival were evaluated using Cox proportional
models that controlled for age and gender. All patients in Group I (201Tl ratio <
2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy
specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio
< 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5
regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%);
they had a 29.2% 1-year survival rate. Almost all of the patients in Group III
(201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and
they had a 6.7% 1-year survival rate. Histological data were associated with 1
year survival (p < 0.01): however, SPECT grouping was more closely associated
with 1-year survival (p < 0.001) and was the only variable significantly
associated with long-term survival (p < 0.005). CONCLUSIONS: Dual-isotope SPECT
data correlate with histopathological findings made at reoperation and with
survival in patients with malignant gliomas after surgical and high-dose
radiation therapy.
PMID- 9647174
TI - Symptomatic pituitary metastases.
AB - OBJECT: The diagnosis and treatment of metastasis to the pituitary gland can be
difficult to determine. The goal of this study was to analyze the clinical
presentation, treatment, and prognosis of patients who presented with symptomatic
pituitary metastasis. METHODS: The cases of 36 patients with symptomatic
pituitary metastases were reviewed. The most common primary cancers were breast
(33%) and lung (36%). The presenting symptoms included diabetes insipidus,
anterior pituitary insufficiency, and retroorbital pain. The overall median
length of patient survival following diagnosis of pituitary metastasis was 180
days. In 20 patients (56%), symptoms stemming from pituitary metastasis were the
first manifestation of illness. Local control of tumor was associated with
significant improvement in survival times (p < 0.05) and amelioration of
disabling symptoms including painful ophthalmoplegia and visual field deficits.
CONCLUSIONS: Aggressive treatment including both surgical decompression and
radiation therapy improves the quality of life in patients suffering from
symptomatic pituitary metastasis.
PMID- 9647175
TI - Endovascular treatment of mural-type vein of Galen malformations.
AB - OBJECT: In this study the authors report on the results of endovascular treatment
for mural-type vein of Galen malformations (VGMs) in a group of infants. METHODS:
Eight children (six infants and two neonates) who suffered from symptoms caused
by a mural-type VGM were treated by means of endovascular therapy. Their age at
the time of treatment ranged from 13 days to 19 months (mean 7.6 months). Two
neonates and three infants who presented with hydrocephalus and increased head
circumference, one of whom was stabilized with a shunt, underwent elective
closure of the malformations 3, 4, 6, 6, and 13 months later, respectively. Two
patients presented with hemorrhage; one had an intraventricular hemorrhage (IVH)
on the 1st day of life and one, a 5-month-old infant, suffered a large
parenchymal hemorrhage and an IVH; both patients were immediately cured by means
of endovascular techniques. One child presented with a seizure and cortical
venous drainage that were treated immediately. Eleven separate treatment sessions
were conducted; eight via transarterial femoral access and the remaining three
via a transvenous approach. Two patients were treated by using transfemoral
transvenous embolization with fibered coils, and one patient required a
transtorcular transvenous approach to permit complete closure of the fistula with
electrolytically detachable coils. The embolic devices used included silk suture
emboli (three patients), electrolytically detachable coils (three patients), and
fibered platinum coils (seven patients). In seven patients, complete closure was
demonstrated on postembolization arteriographic studies. The eighth patient had
stagnant flow in a giant 6-cm varix treated with arterial and venous coils but
has not yet undergone follow-up studies. Late follow-up arteriography was
performed in four patients at times ranging from 11 to 24 months postprocedure.
In one patient, thrombosis of the malformation and shrinkage of the varix were
confirmed on follow-up computerized tomography scanning. The remaining three
patients have not yet undergone follow-up angiographic examination. Two
asymptomatic complications occurred, including separation of the distal catheter,
which was removed with a snare device, and a single platinum coil that embolized
to the lung, producing no symptoms in 101 months of clinical follow up. The
follow-up period ranged from 3 to 105 months, with a mean of 52 months.
CONCLUSIONS: Endovascular therapy is the treatment of choice for mural-type VGMs
and offers a high rate of cure with low morbidity.
PMID- 9647176
TI - Endovascular embolization of 150 basilar tip aneurysms with Guglielmi detachable
coils: results of the Food and Drug Administration multicenter clinical trial.
AB - OBJECT: To assess the safety and efficacy of aneurysm embolization performed
using Guglielmi detachable coils (GDCs), the authors reviewed the results of a
cohort of 150 patients with either ruptured (83 patients) or unruptured (67
patients) basilar tip aneurysms treated with these detachable platinum coil
devices in the early part of the United States multicenter GDC clinical trial
that led to Food and Drug Administration approval for the device. METHODS: The
most common presentation in this cohort of patients was headache (53%). All
patients were entered into the trial after neurosurgical assessment excluded them
as candidates for surgical clipping of their aneurysms. Greater than 90% coil
packing was achieved in 75% of the patients. For those patients in whom follow-up
information was available, the mean angiographic and clinical evaluation follow
up time for 61 patients with ruptured aneurysms was 13.7 months (range 0-43
months) and that for the 49 patients with unruptured aneurysms was 9.8 (range 0
40 months). Conservative mortality rates included up to 23% for the ruptured
aneurysm group and up to 12% for the unruptured aneurysm group; the rebleeding
rate for treated ruptured aneurysms was up to 3.3% and the bleeding rate for
unruptured aneurysms up to 4.1%. Permanent deficits due to stroke in patients
with ruptured or unruptured aneurysms occurred in up to 5% and 9%, respectively.
Vasospasm occurred in 8% of the patients; it was associated with two deaths.
Periprocedural mortality was 2.7% (four patients with ruptured aneurysms).
CONCLUSIONS: Detachable platinum coil embolization is a promising treatment for
ruptured basilar tip aneurysms that are not surgically clippable; in selected
patients it offers lower incidences of morbidity and mortality compared with
conservative medical management. The role of this procedure in unruptured basilar
tip aneurysms is unclear with less supportive results. More long-term follow-up
evaluation is necessary and results are expected to improve.
PMID- 9647177
TI - Causes and management of aneurysmal hemorrhage occurring during embolization with
Guglielmi detachable coils.
AB - OBJECT: The purpose of this review is to describe the incidence, causes,
management, and outcome of aneurysmal hemorrhage that occurred in patients during
endovascular treatment with the Guglielmi detachable coil (GDC) system. METHODS:
At the authors' institution between September 1991 and August 1995, more than 200
patients were treated using GDCs for intracranial aneurysms. The first 200
patients treated in this fashion were reviewed and all who experienced new
subarachnoid hemorrhage (SAH) during the procedure were identified. Angiographic
studies were also reviewed and patients were contacted for longer-term follow up
when possible. Four patients who experienced intraprocedural SAH were identified.
The causes of hemorrhage were believed to be perforation of the aneurysm by the
guidewire in one patient, perforation by the microcatheter in a second, and
perforation by the delivery wire in a third. The fourth patient had a hemorrhage
during injection of contrast material for control angiographic studies after
placement of the final coil. One patient died, but the other three experienced no
neurological symptoms or recovered without acquiring additional deficits. Overall
a procedural hemorrhage rate of 2% was seen, with permanent morbidity and
mortality rates of 0% and 0.5%, respectively. CONCLUSIONS: Although SAH during
endovascular treatment of intracranial aneurysms remains a significant risk, its
incidence is low and a majority of patients can survive without serious sequelae.
PMID- 9647178
TI - Improvement of cerebral oxygenation patterns and metabolic validation of
superselective intraarterial infusion of papaverine for the treatment of cerebral
vasospasm.
AB - OBJECT: The purpose of the present study was to assess cerebral oxygenation
patterns and brain lactate concentration changes before, during, and after
intraarterial infusion of papaverine with or without balloon angioplasty in
patients with symptomatic vasospasm. METHODS: A total of 23 vascular territories
were successfully treated in 10 patients. In three patients balloon angioplasty
was performed before the papaverine infusion. Continuous monitoring of jugular
bulb vein oxygen saturation with a fiberoptic catheter and blood sampling allowed
the assessment of the cerebral arteriovenous oxygen and lactate differences. A
significant and rapid improvement in jugular bulb oxygen saturation was observed
in all cases, with critical values reflecting an improvement in cerebral
oxygenation after endovascular treatment of vasospasm (p = 0.005). Lactate
concentration in the jugular bulb normalized within 4 hours in all patients who
had evidence of brain lactic acidosis before superselective intraarterial
infusion of papaverine. Recurrence of abnormal metabolic and oxygenation patterns
were observed in one case in which an optimal hypertension and hypervolemic
therapy could not be achieved after the procedure. CONCLUSIONS: Improvement in
cerebral oxygenation as well as prevention of cerebral lactic acidosis can be
successfully achieved after intraarterial infusion of papaverine. Normalization
of the oxygen supply after endovascular treatment has to be supported by optimal
and well-monitored hypertension and hypervolemic hemodilution.
PMID- 9647179
TI - Seasonal pattern of spontaneous cervical artery dissection.
AB - OBJECT: The etiology of spontaneous cervical artery dissection is poorly
understood; however, it may involve genetic and environmental factors. The
purpose of this study was to determine whether seasonality of spontaneous
cervical artery dissection exists. METHODS: The seasonal pattern of spontaneous
cervical artery dissection was analyzed in a group of 200 consecutive patients
(104 females and 96 males with a mean age of 44.9 years) who were evaluated using
the Rayleigh test during the period from 1970 to 1990. The majority of patients
resided in the midwestern section of the United States, where large seasonal
fluctuations in climate occur. A circannual periodicity was found in the
frequency of spontaneous cervical artery dissections with a peak occurring in
October (p < 0.02). The seasonal variation was substantial, with approximately
58% more patients suffering a cervical artery dissection during autumn than
during other seasons. CONCLUSIONS: A seasonal pattern of spontaneous cervical
artery dissection exists with a peak occurring in October. The cause of the
seasonality remains to be explained; however, weather- or infectious disease
related factors may provide etiological leads.
PMID- 9647180
TI - Analysis of treatment failure after radiosurgery for arteriovenous malformations.
AB - OBJECT: The aim of this study was to evaluate the causes of treatment failure in
patients with arteriovenous malformations (AVMs) who underwent radiosurgery,
which is increasingly used as a treatment method for selected, surgically high
risk AVMs. Unfortunately, radiosurgical treatment fails in a small but
significant percentage of patients. In the time period covered in this study, 72
patients attained angiographically confirmed cures after radiosurgery and 36 were
retreated after the initial radiosurgical treatment failed. METHODS: Using a
computerized image fusion technique, the initial radiosurgical dosimetry plan was
superimposed on the remaining AVM nidus at the time of retreatment. Twenty-six
percent of the retreated cases were found to have AVM niduses outside the
original treatment isodose line, which means that targeting error was a factor.
The retreated group was also statistically compared with the cured group.
CONCLUSIONS: Multivariate analysis revealed that the following factors were
statistically significant predictors of treatment failure: increasing AVM size,
decreasing treatment dose, and increasing Spetzler-Martin grade.
PMID- 9647181
TI - The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by
cyclic adenosine monophosphate.
AB - OBJECT: This study was designed to determine whether subarachnoid hemorrhage
(SAH) affects the function of the K+ channels responsible for relaxation of
canine cerebral arteries in response to adenylate cyclase activation. METHOD: The
effect of K+ channel inhibitors on the arterial relaxation response to forskolin,
a direct adenylate cyclase activator, was studied in rings of basilar arteries
obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage
model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured
using the radioimmunoassay technique. In rings with the endothelium removed,
relaxation induced by forskolin was not affected by SAH. The relaxation response
to forskolin was reduced by charybdotoxin (10(-7) mol/L), a selective Ca++
activated K+ channel inhibitor, in normal arteries and arteries subjected to
autologous blood injection. This inhibitory effect of charybdotoxin was
significantly greater in arteries involved in SAH than in normal vessels. The
relaxation response to forskolin was reduced by 4-aminopyridine (10(-3) mol/L), a
delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In
contrast, the relaxation response to forskolin was not affected by glyburide (10(
5) mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both
normal and SAH arteries. Forskolin (3 x 10(-7) mol/L) produced an approximately
10-fold increase in levels of cAMP. The basal values and increased levels of cAMP
detected after stimulation with forskolin were no different in normal arteries
and those exposed to SAH. CONCLUSIONS: These results demonstrate that formation
of cAMP and the relaxation response to adenylate cyclase activation are not
affected by SAH. However, in diseased arteries, K+ channels assume a more
important role in the mediation of relaxation response to forskolin, indicating
that SAH may change the mechanisms responsible for vasodilation induced by cAMP.
PMID- 9647182
TI - Local cerebral blood flow autoregulation following "asymptomatic" cerebral venous
occlusion in the rat.
AB - OBJECT: Maintenance of cerebral blood flow (CBF) autoregulation in the brain is
of major importance for patient outcome in various clinical conditions. The
authors assessed local autoregulation after "asymptomatic" cortical vein
occlusion. METHODS: In Wistar rats, a single cortical vein was occluded
photochemically by using rose bengal and fiberoptic illumination. In rats with
bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was
lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension.
Local CBF at each pressure level was assessed by performing laser Doppler (LD)
scanning at 25 (5 x 5) locations within bilateral cranial windows. In this
manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm
Hg in both right and left hemispheres in Group A (five rats), in which the
animals received illumination without rose bengal and had no venous occlusion. Of
the 11 rats that underwent vein occlusion, three developed severe reductions in
local CBF and/or a growing venous thrombus and were distinguished as Group C
(symptomatic; three rats); from previous work we know that those animals are
bound to experience venous infarction. The remaining rats formed Group B
(asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the
left hemisphere without occlusion, whereas, in the right cortex with the occluded
vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm
Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly
ischemic range than that in the opposite normal hemisphere. CONCLUSIONS: The
results of the present study suggest that cerebral venous circulation disorders
are manifested via additional pathways, that is, from a partially impaired local
autoregulation in the vicinity of the occluded vein, even under conditions in
which the vein occlusion itself does not cause brain damage. Care should be taken
in the control of blood pressure in patients with this pathological condition.
PMID- 9647183
TI - Enhancement of radiosensitivity of wild-type p53 human glioma cells by adenovirus
mediated delivery of the p53 gene.
AB - OBJECT: The authors sought to determine whether combining p53 gene transfer with
radiation therapy would enhance the therapeutic killing of p53 wild-type glioma
cells. It has been shown in several reports that adenovirus-mediated delivery of
the p53 gene into p53 mutant gliomas results in dramatic apoptosis, but has
little effect on gliomas containing wild-type p53 alleles. Therefore, p53 gene
therapy alone may not be a clinically effective treatment for gliomas because
most gliomas are composed of both p53 mutant and wild-type cell populations. One
potential approach to overcome this problem is to exploit the role p53 plays as
an important determinant in the cellular response to ionizing radiation. METHODS:
In vitro experiments were performed using the glioma cell line U87MG, which
contains wild-type p53. Comparisons were made to the glioma cell line U251MG,
which contains a mutant p53 allele. Monolayer cultures were infected with an
adenovirus containing wild-type p53 (Ad5CMV-p53), a control vector (dl312), or
Dulbecco's modified Eagle's medium (DMEM). Two days later, cultures were
irradiated and colony-forming efficiency was determined. Transfection with p53
had only a minor effect on the plating efficiency of nonirradiated U87MG cells,
reducing the plating efficiency from 0.23 +/- 0.01 in DMEM to 0.22 +/- 0.04 after
addition of Ad5CMV-p53. However, p53 transfection significantly enhanced the
radiosensitivity of these cells. The dose enhancement factor at a surviving
fraction of 0.10 was 1.5, and the surviving fraction at 2 Gy was reduced from
0.61 in untransfected controls to 0.38 in p53-transfected cells. Transfection of
the viral vector control (dl312) had no effect on U87MG radiosensitivity. In
comparison, transfection of Ad5CMV-p53 into the p53 mutant cell line U251 MG
resulted in a significant decrease in the surviving fraction of these cells
compared with controls, and no radiosensitization was detected. To determine
whether Ad5CMV-p53-mediated radiosensitization of U87MG cells involved an
increase in the propensity of these cells to undergo apoptosis, flow cytometric
analysis of terminal deoxynucleotidyl transferase-mediated biotinylated
deoxyuridinetriphosphate nick-end labeling-stained cells was performed. Whereas
the amount of radiation-induced apoptosis in uninfected and dl312-infected
control cells was relatively small (2.1 +/- 0.05% and 3.7 +/- 0.5%,
respectively), the combination of Ad5CMV-p53 infection and radiation treatment
significantly increased the apoptotic frequency (18.6 +/- 1.4%). To determine
whether infection with Ad5CMV-p53 resulted in increased expression of functional
exogenous p53 protein, Western blot analysis of p53 was performed on U87MG cells
that were exposed to 9 Gy of radiation 2 days after exposure to Ad5CMV-p53,
dl312, or DMEM. Infection with Ad5CMV-p53 alone increased p53 levels compared
with DMEM- or dl312-treated cells. Irradiation of AdSCMV-p53-infected cells
resulted in a further increase in p53 that reached a maximum at 2 hours
postirradiation. To determine whether exogenous p53 provided by Ad5CMV-p53 had
transactivating activity, U87MG cells were treated as described earlier and p21
messenger RNA levels were determined. Infection of U87MG cells with Ad5CMV-p53
only resulted in an increase in p21 compared with DMEM- and dl312-treated cells.
Irradiation of AdSCMV-p53-infected cells resulted in an additional time-dependent
increase in p21 expression. CONCLUSIONS: These data indicate that adenovirus
mediated delivery of p53 may enhance the radioresponse of brain tumor cells
containing wild-type p53 and that this radiosensitization may involve converting
from a clonogenic to the more sensitive apoptotic form of cell death. Although
the mechanism underlying this enhanced apoptotic susceptibility is unknown, the
AdSCMV-p53-infected cells have a higher level of p53 protein, which increases
further after irradiation, and this exogenous p53 is transcriptionally active.
(ABSTRACT TRUNCATE
PMID- 9647184
TI - Ninety-degree rotation of the thoracic spinal thecal sac. Case report.
AB - This 44-year-old man presented with a 4-year history of progressive spastic
weakness of his legs. He was found to have epidural lipomatosis behind the
thoracic spinal cord, and the nerve roots exited from the posterior and anterior
midline planes of the dura, indicating a 90 degree rotation of the thoracic cord.
Magnetic resonance images clearly demonstrated the segmental thoracic nerve roots
exiting from the dorsal midline of the dura, a finding confirmed at surgery. The
authors found only one previously published case of rotation of the spinal cord.
Directed mechanical stress caused by deformation of the rotated spinal cord,
rather than compression from adipose tissue, is proposed as the mechanism of the
myelopathy. The extent, location, and thickness of the associated extradural
adipose tissue is suggestive of epidural lipomatosis. The lipomatous tissue might
have been an epiphenomenon and cord rotation an isolated congenital anomaly.
Alternatively, asymmetrical growth of epidural fat may have exerted torque,
rotating the thecal sac.
PMID- 9647185
TI - Familial cervical spondylosis. Case report.
AB - Cervical spondylosis is a disease that is often attributed to aging and
considered the result of degenerative changes in the spine. The idea that there
is a genetic predisposition to develop diseases of the skeletal elements of the
spine has been discussed previously, but has never been proven conclusively. The
authors report three cases of severe cervical spondylosis in patients who are
first-degree relatives: a mother and her two sons. All three individuals had
cervical disc herniations and stenosis at C3-4, C4-5, C5-6, and C6-7, and all
three required decompressive procedures. The location and degree of cervical
spondylosis were as similar among these three patients as they have been in
identical twins reported in other studies. Such familial inheritance of cervical
spondylosis has been reported only once. The existence of familial cervical
spondylosis is not an unrealistic proposal because other studies have shown that
genetics determines the shape of one's spine and that similar spines tend to
degenerate in similar ways. Therefore, genetic counseling for a family such as
the one reported here may prove to be of great benefit to warn siblings that they
are at high risk for cervical spine injury. However rare it might be, familial
cervical spondylosis may be a phenomenon that any spine surgeon should suspect in
a family with cervical spine abnormalities found in several members.
PMID- 9647186
TI - Delayed aneurysm regrowth and recanalization after Guglielmi detachable coil
treatment. Case report.
AB - Guglielmi detachable coil (GDC) treatment for complicated cerebral aneurysms is
an attractive option that has become widely accepted in recent years. This
technique is usually considered only if the patient harbors an aneurysm that is
not a good candidate for surgical clipping. However, the definition of "surgical
candidate" varies among institutions, and many patients worldwide are being
treated with GDCs as primary therapy. Although most centers currently perform
follow-up angiography at 6 months to 1 year, others do not routinely perform it
after an initially good result. The authors present a case that indicates longer
follow up may be necessary and illustrates some of the pitfalls of GDC treatment.
This 56-year-old man presented to the emergency room with a Hunt and Hess Grade
II subarachnoid hemorrhage and was found to have a wide-necked basilar apex
aneurysm. Because of associated medical comorbidities, it was decided to treat
the aneurysm with endovascular techniques. The patient did well on follow-up
angiography at 1 year postprocedure. However, at approximately 2 years follow up,
the aneurysm was demonstrated to have dramatically recanalized and regrown,
requiring open surgical intervention. Endovascular coiling was insufficient to
treat this aneurysm and complicated definitive surgical management because a
large coil mass had been placed in the operative field. It can be inferred from
this case that angiographic follow up of these types of lesions may be beneficial
up to 2 years after GDC treatment.
PMID- 9647187
TI - Suprasellar tension pneumocyst after transsphenoidal surgery. Case report.
AB - Tension pneumocephalus is an uncommon occurrence after transsphenoidal surgery.
The author presents an unusual case of postoperative visual deterioration related
to expanding air within a suprasellar tumor cavity.
PMID- 9647188
TI - Neurofibromatosis type 2: growth stimulation of mixed acoustic schwannoma by
concurrent adjacent meningioma: possible role of growth factors. Case report.
AB - The authors report the case of a young man suffering from neurofibromatosis type
2 (NF2) who harbored bilateral acoustic schwannomas and a parasellar meningioma.
Neuroimaging studies performed during a 4-year follow-up period showed that the
bilateral schwannomas had grown very little and at similar rates. However, after
the meningioma had infiltrated the tentorium and approached the ipsilateral
schwannoma at the incisura, both Schwann cell tumors started to grow rapidly,
particularly the one adjacent to the meningioma, of which the percentage of
annual growth rate increased by approximately a factor of 10(2). At the same
time, magnetic resonance imaging showed that this tumor also changed its
features. During surgery, the acoustic schwannoma was firmly adherent to both
meningioma and tentorium. Histological examination revealed meningotheliomatous
cells in the schwannoma adjacent to the meningioma. Antiphosphotyrosine
immunoblotting of PC12 cells was compatible with the presence of an epidermal
growth factor (EGF)-like molecule in the cerebrospinal fluid (CSF) of the
patient. This factor was not detected in the CSF of five other NF2 patients, two
of whom bore associated bilateral acoustic schwannomas and meningioma in remote
locations. It is hypothesized that the meningotheliomatous cells infiltrating the
schwannoma triggered an autocrine/paracrine growth-stimulatory mechanism that
involved an EGF-like factor.
PMID- 9647189
TI - Use of ligamentum nuchae graft for dural closure in posterior fossa surgery.
Technical note.
AB - The technique of harvesting the ligamentum nuchae and its use in posterior fossa
surgery are discussed. By using this technique the author has avoided
postoperative cerebrospinal fluid leakage in more than 200 procedures.
PMID- 9647190
TI - Posterior ventricular catheter burr-hole localizer. Technical note.
AB - Proper ventricular catheter placements are associated with improved shunt
performance. When placing ventricular catheters via the posterior approach, the
surgeon must determine an optimum trajectory and then pass a catheter along that
trajectory. The incidence of optimal posterior catheter placements is increased
by using a posterior catheter guide (PCG); however, errors may still occur
because of poor selection of a posterior burr-hole site. In this report an easy
to-use posterior burr-hole localizer (Localizer) is described that defines the
optimum burr-hole location based on geometric relationships involving the ear and
supraorbital rims. The basic design principle of the Localizer was formulated and
tested by using neuronavigational imaging tools to examine normal adult
ventricular anatomy in relation to surface landmarks and by reviewing imaging
studies obtained in 50 adult patients with hydrocephalus. Subsequently, the
Localizer was used in 28 consecutive patients scheduled to undergo shunt surgery
performed by using the PCG. In all cases the catheter entered the ventricle on
the first pass and postoperative imaging studies demonstrated successful
placement in the ipsilateral anterior horn. There were no catheter-related
complications. These early results indicate that the Localizer and PCG devices
may be safe and effective when used in combination for placement of posterior
ventricular catheters.
PMID- 9647191
TI - Giant nasal schwannoma with intracranial extension. Case illustration.
PMID- 9647192
TI - Tumor growth rates.
PMID- 9647193
TI - Radiation-induced cavernous malformation.
PMID- 9647194
TI - Medullary compression and hypertension.
PMID- 9647195
TI - Arteriovenous malformations after radiosurgery.
PMID- 9647196
TI - Arteriovenous malformations after radiosurgery.
PMID- 9647197
TI - Meningeal melanocytoma.
PMID- 9647198
TI - Intraventricular chemotherapy.
PMID- 9647199
TI - TRANK, a novel cytokine that activates NF-kappa B and c-Jun N-terminal kinase.
AB - We searched the expressed sequence tag database using sequence homology and
identified a novel cytokine, which we have named TRANK (thioredoxin peroxidase
related activator of NF-kappa B and c-Jun N-terminal kinase). The predicted amino
acid sequence of TRANK was highly homologous to that of the thiol-specific
antioxidant proteins. Unlike these proteins, however, TRANK had a putative
secretory signal polypeptide and was found to be secreted by cells. TRANK was
expressed in most tissues and cell lines, and the gene that encodes it was mapped
to chromosome Xp21-22.1. TRANK activated NF-kappa B and induced the degradation
of the inhibitory subunit of NF-kappa B. In addition, TRANK up-regulated the
expression of NF-kappa B-dependent gene products, ICAM-1, and inducible nitric
oxide synthase. TRANK also activated c-Jun N-terminal kinase and induced the
proliferation of normal human foreskin fibroblasts. Its homology with antioxidant
proteins, wide distribution in tissues, and ability to activate NF-kappa B and c
Jun N-terminal kinase suggest that TRANK plays an important role in inflammation.
PMID- 9647200
TI - Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors.
AB - Several members of the Ly-49 receptor family inhibit NK cell-mediated lysis of
targets expressing appropriate MHC class I molecules. Ly-49D and Ly-49H, two Ly
49 molecules that lack immunoreceptor tyrosine-based inhibitory motifs (ITIM) in
their cytoplasmic domains, associate with mouse DAP12, a molecule that possesses
an immunoreceptor tyrosine-based activation motif (ITAM). Cotransfection of
either Ly-49D or Ly-49H with DAP12 induces surface expression of both Ly-49 and
DAP12. The Ly-49/DAP12 complex was coimmunoprecipitated from the transfected
cells, demonstrating a physical association of DAP12 with Ly-49D or Ly-49H in the
plasma membrane. Stimulation of transfectants with Abs recognizing either Ly-49D
or Ly-49H results in cellular activation, as assessed by induction of tyrosine
phosphorylation of multiple cellular substrates.
PMID- 9647201
TI - The expression in vivo of a second isoform of pT alpha: implications for the
mechanism of pT alpha action.
AB - A second isoform of pT alpha, "pT alpha(b)," is derived from the pT alpha locus
by tissue-specific, alternative splicing. pT alpha(b) is coexpressed in the
thymus with the previously characterized form of pT alpha (which we term pT
alpha(a)) and is also expressed in peripheral cells without pT alpha(a). While pT
alpha(a) acts to retain most TCR beta-chains intracellularly, pT alpha(b) permits
higher levels of cell surface TCR beta expression and facilitates signaling from
a CD3-TCR beta complex.
PMID- 9647202
TI - Differences in the immune response during the acute phase of E-55+ murine
leukemia virus infection in progressor BALB and long term nonprogressor C57BL
mice.
AB - E-55+ murine leukemia virus infection of both progressor (BALB) and long term
nonprogressor (C57BL) mouse strains is characterized by an acute and a persistent
phase of infection. During the acute phase, progressor strains require CD8+ T
cells to decrease virus burden, whereas the long term nonprogressor strains do
not. In the present studies the immune response in BALB and C57BL mice during the
acute phase of E-55+ murine leukemia virus infection was examined. The results
demonstrate that BALB mice produce both IL-4 and IFN-gamma, in contrast to C57BL
mice, which produce only IFN-gamma. In BALB mice, IL-4 production results in the
absolute requirement for CD8+ T cells to reduce the virus burden during the acute
phase of infection. The anti-virus immune response in these mice is IFN-gamma
dependent. On the other hand, C57BL mice do not produce IL-4 and, in the absence
of both CD8+ T cells and IFN-gamma, still generate an effective anti-virus immune
response. Genetic studies suggest that these distinct immune responses are
regulated by more than one non-MHC-linked gene. Two candidate regions that may
encode this gene(s), located on chromosomes 7 and 19, respectively, were
identified by recombinant inbred strain linkage analysis.
PMID- 9647203
TI - The role of estrogen receptors and androgen receptors in sex steroid regulation
of B lymphopoiesis.
AB - Several observations suggest that sex steroids might participate in steady state
regulation of B lymphopoiesis. B cell precursors decline dramatically in bone
marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell
populations are increased in hypogonadal mice or male castrates. Estrogen
treatment of hypogonadal mice reduced precursors to normal. However, questions
remain about which hormones and receptors are the most important. Furthermore,
these observations need to be reconciled with advances regarding new sex steroid
receptors. We have now characterized B lymphopoiesis in androgen receptor
deficient testicular feminization (Tfm) mice. Testicular feminization mice had
substantially elevated numbers of B cell precursors in the bone marrow and B
cells in the spleen as compared with wild-type mice. The importance of one
estrogen receptor (ER alpha) was evaluated in gene-targeted mice, and B cell
precursors were found to be within the normal range. Our previous studies
indicated that hormone receptors in stromal cells may be important for estrogen
mediated suppression of B lymphopoiesis. We now show that estrogen-mediated
inhibition of B cell precursor expansion in culture was blocked by a specific
estrogen receptor antagonist (ICI 182,780). Stromal cells derived from ER alpha
targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these
stromal cells revealed splice-variant transcripts of ER alpha, as well as message
for a recently discovered estrogen-binding receptor, ER beta. Thus, androgens may
normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens
might utilize one or more receptors to achieve the same physiologic response.
PMID- 9647204
TI - Proteasome activation occurs at an early, premitochondrial step of thymocyte
apoptosis.
AB - Proteasomes and mitochondrial membrane changes are involved in thymocyte
apoptosis. The hierarchical relationship between protease activation and
mitochondrial alterations has been elusive. Here we show that inhibition of
proteasomes by two specific agents, lactacystin or MG132, prevents all
manifestations of thymocyte apoptosis induced by the glucocorticoid receptor
agonist dexamethasone or by the topoisomerase II inhibitor etoposide. Lactacystin
and MG132 prevent the early disruption of the mitochondrial transmembrane
potential (delta psi(m)), which precedes caspase activation, exposure of
phosphatidylserine, and nuclear DNA fragmentation. In contrast, stabilization of
the delta psi(m) using the permeability transition pore inhibitor bongkrekic acid
or inhibition of caspases by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
does not prevent the activation of proteasomes, as determined with the
fluorogenic substrate N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4
methylcoumarin . Thus, proteasome activation occurs upstream from mitochondrial
changes and caspase activation. Whereas the proteasome-specific agents
lactacystin and MG132 truly maintain thymocyte viability, a number of protease
inhibitors that inhibit nuclear DNA fragmentation (acetyl-Asp-Glu-Val-Asp
fluoromethylketone; N-Boc-Asp(OMe)-fluoromethylketone; N-tosyl-L-Phe
chloromethylketone) do not prevent the cytolysis induced by DEX or etoposide.
These latter agents fail to interfere with the preapoptotic delta psi(m)
disruption. Altogether, our data indicate that different proteases may be
involved in the pre- or postmitochondrial phase of apoptosis. Only those protease
inhibitors that interrupt the apoptotic process at the premitochondrial stage can
actually preserve cell viability.
PMID- 9647205
TI - Repertoire analysis of CD8+ T cell responses to minor histocompatibility antigens
involved in graft-versus-host disease.
AB - Graft-vs-host disease (GVHD) is a major complication of allogeneic bone marrow
transplantation. Experimentally, lethal GVHD can be induced in MHC-matched strain
combinations differing in expression of multiple minor histocompatibility Ags
(miHA). Recently, the GVHD potential of C57BL/6By (B6) T cells in irradiated
BALB.B (both H2b) and related CXB recombinant inbred strains of mice has been
studied to determine the scope of the response to miHA in vivo and how it
compared with CTL responses to immunodominant miHA in vitro. The GVHD response in
these strain combinations appeared to be limited to a few Ags, yet there was no
correlation of these miHA with that of in vitro CTL responses. To further
investigate the role of CD8+ T cells in GVHD, we analyzed positively selected
miHA-specific donor CD8+ thoracic duct lymphocytes (TDL) collected from
irradiated BALB.B and CXBE mice, 5 to 6 days after transplantation of B6 T cells.
Flow cytometric analysis of B6-->BALB.B TDL did not indicate expansion of any
particular TCR Vbeta family, whereas Vbeta10 and Vbeta14 families were
significantly expanded in the B6-->CXBE TDL. However, PCR-based complementarity
determining region 3 size spectratyping revealed overlapping involvement of donor
Vbeta1, 6, 8, 9, 10, and 14 families in both BALB.B and CXBE recipients and
unique utilization of the Vbeta4 family in BALB.B mice, suggesting oligoclonal T
cell responses to a limited number of miHA. In addition, the injection of CD8+
Vbeta14+ B6 T cells into irradiated BALB.B and CXBE mice induced lethal GVHD,
confirming the involvement of miHA-specific T cells within an individual Vbeta
family.
PMID- 9647206
TI - Requirements for B7-CD28 costimulation in mucosal IgA responses: paradoxes
observed in CTLA4-H gamma 1 transgenic mice.
AB - The block in the CD80/CD86-CD28/CTLA-4 pathway in CTLA4-H gamma 1 transgenic (Tg)
mice results in strongly impaired systemic IgG immunity and failure to develop
germinal center reactions. By contrast, here we report that mucosal immunity and
IgA B cell differentiation are not affected by this block. We found abundant
germinal centers and evidence of IgA switch differentiation in Peyer's patches,
normal total IgA levels, and normal numbers of IgA-labeling cells in the gut
mucosa. The distribution of B-1 and B-2 cells and the relative contribution of B
1 cells to the total IgA B cells were similar in Tg and wild-type mice. Despite
this, oral immunizations with keyhole limpet hemocyanin plus cholera toxin
adjuvant failed to stimulate Ag-specific mucosal IgA responses in CTLA4-H gamma 1
Tg mice. This was not due to a lack of adjuvant activity of cholera toxin in Tg
mice, nor was this secondary to an inability to take up Ag from the gut lumen.
Rather, CD4+ T cells stimulated by oral immunization in Tg mice appeared to be
inappropriately primed, as evidenced by a significantly reduced level of CD40
ligand and CD44 expression and an increased expression of CD95 compared to those
in wild-type mice. This study reveals a paradox in the regulation of mucosal IgA
responses.
PMID- 9647207
TI - A viral peptide with limited homology to a self peptide can induce clinical signs
of experimental autoimmune encephalomyelitis.
AB - Molecular mimicry has been suggested as a mode of autoreactive T cell stimulation
in autoimmune diseases. Myelin basic protein (MBP) peptide 1-11 induces
experimental autoimmune encephalomyelitis (EAE) in susceptible strains of mice.
Here we show that a herpesvirus Saimiri (HVS) peptide, AAQRRPSRPFA, with a
limited homology to MBP1-11 peptide, ASQKRPSQRHG (underlined letters showing
homology), can stimulate a panel of MBP-11-specific T cell hybridomas and more
importantly cause EAE in mice. We demonstrate that this is due to cross
recognition of these two peptides by TCRs. Results presented in this
communication are the first demonstration that a viral peptide with homology at
just 5 amino acids with a self peptide can induce clinical signs of EAE in mice.
These findings have important implications in understanding the breakdown of T
cell tolerance to self Ags in autoimmune diseases by means of cross-reactivity
with unrelated peptides.
PMID- 9647208
TI - Pentoxifylline inhibits adhesion and activation of human T lymphocytes.
AB - We have herein studied the effect of pentoxifylline (PTX) on the adhesion and
activation of human T lymphocytes. We found that PTX inhibited the adhesion of T
cells to the beta1 and beta2 integrin ligands VCAM-1 and ICAM-1; this inhibitory
activity was dose dependent, with a maximal effect from 12 to 24 h. We also found
that PTX was able to interfere with the activation of beta1 integrins induced by
intracellular signals; however, the conformational change of beta1 integrins
induced by extracellular stimuli (e.g., activating mAbs, or Mn2+) was not
significantly affected by this drug. In addition, the homotypic aggregation of T
cells induced by anti-beta1 and -beta2 integrin chain mAbs was also inhibited by
PTX. PTX had a significant inhibitory effect on the T lymphocyte expression of
the activation Ags CD25 (IL-2R alpha-chain), CD69 (activation-inducer molecule),
and CD98 (4F2) induced by PHA. Accordingly, PTX also interfered with early cell
activation events such as the rise in intracellular Ca2+ and the activation of
the Na+/H+ antiporter induced by PHA and phorbol esters, respectively.
Furthermore, this drug inhibited both the cell cycle progression and cell
proliferation of T cells induced through the CD3/TCR complex. However, this drug
did not show any effect on the cell activation/proliferation induced by PMA plus
ionomycin. Our results indicate that PTX interferes efficiently with the
activation and cell adhesion of human T lymphocytes. These effects may be of
relevance for the clinical uses of this drug.
PMID- 9647209
TI - De novo-developed T cells have compromised response to existing alloantigens:
using Ld-specific transgenic 2C T cells as tracers in a mouse heart
transplantation model.
AB - In this study, the phenotype, TCR signaling events, and function of T cells
developed de novo during adulthood in the presence of extrathymic alloantigen
were investigated. C57BL/6 mice(H-2b) were first transplanted heterotopically
with BALB/c hearts (H-2d) and treated with rapamycin for 2 wk to create a
tolerant status. Three weeks postoperation, the mice were whole body irradiated
and transplanted with bone marrow cells from 2C mice, which are transgenic for
TCR, and most of their T cells are Ld-specific CD8 cells. The 2C T cells
developed de novo in the C57BL/6 mice were not able to reject the heart
allograft. No clonal deletion, TCR down-regulation, or CD8 down-regulation was
found in the tolerized 2C T cells. There was no characteristic phenotype of these
cells in terms of CD25, ICAM-1, CD44, and MEL-14 expression. Early TCR signaling
events such as intracellular calcium concentration flux, tyrosine
phosphorylation, Lck and Fyn kinase activities, and Lck and Fyn protein levels in
the tolerized 2C T cells were comparable to their normal counterparts, but the
tolerized T cells were defective in IL-2 production and proliferation upon H-2d
alloantigen stimulation in vitro. Exogenous IL-2 could not reverse the
compromised proliferation. The results of this study indicate that during
adulthood, the de novo-developed T cells become tolerant to extrathymic Ag
without clonal deletion. These newly minted T cells are functionally defective
although they are indistinguishable from normal T cells in phenotypes and in some
early signaling events.
PMID- 9647210
TI - Allelic differences in the relationship between proteasome activity and MHC class
I peptide loading.
AB - MHC class I molecules are cell surface glycoproteins that play a pivotal role in
the response to intracellular pathogens. The loading of MHC class I molecules
with antigenic substrates takes place in the endoplasmic reticulum. This requires
a functional TAP transporter, which translocates peptides into the endoplasmic
reticulum from the cytosol. The generation of antigenic peptides from polypeptide
precursors is thought to be mediated in the cytosol by the proteasome.
Previously, we have demonstrated that inhibiting the proteasome with the specific
covalent inhibitor lactacystin results in a direct reduction of peptide-loaded
MHC class I molecules. This indicates that the proteasome is the limiting step in
the MHC class I pathway. In this study we use isoelectric focusing to demonstrate
that two related MHC class I alleles, HLA-A3 and HLA-A11, as well as HLA-B35 do
not follow this behavior. In contrast to other class I alleles expressed by the
same cells, these alleles are loaded with peptides and mature normally when
proteasome activity is severely inhibited. Our observations highlight a new level
of diversity in the MHC class I system and indicate that there are allele
specific differences in the linkage between proteasome activity and MHC class I
peptide loading.
PMID- 9647211
TI - H2-M3 presents a nonformylated viral epitope to CTLs generated in vitro.
AB - Most CTL responses to epitopes from influenza virus are restricted by MHC class
Ia molecules. However, a synthetic peptide corresponding to residues 173 to 190
of influenza A/JAP/305/57 hemagglutinin (HA) can induce, in vitro, a CTL response
to peptide presented by a mouse class Ib molecule encoded by a gene telomeric to
H2-Q. Here, we identify the molecule as H2-M3 and show that the last five
residues of HA173-190, MLIIW, is the minimal epitope for CTL recognition. Cells
that express M3wt, from C57BL/6 or BALB/c mice, are sensitized by both MLIIW and
the longer peptide HA173-190, whereas cells that express M3f, from A.CA or B10.M
mice, are sensitized only by MLIIW; a single amino acid change at residue 31 (V-
>M) of M3 accounts for this difference. Although M3-restricted CTLs preferably
recognize N-formylated epitopes, i.e., those of mitochondrial or prokaryotic
origin, our findings show that M3-restricted primary CTL responses can be
generated in vitro against nonformylated epitopes.
PMID- 9647212
TI - In vivo persistence of CD8 polarized T cell subsets producing type 1 or type 2
cytokines.
AB - Naive CD8 T cells can be polarized into effectors producing the type 1 cytokines
IFN-gamma and IL-2 or the type 2 cytokines IL-4, IL-5, and IL-10, respectively.
To study whether the polarized cytokine phenotype of the effectors is stable, we
generated highly cytotoxic hemagglutinin (HA) peptide-specific CD8 Tc1 and Tc2
(cytotoxic CD8 T cells producing type 1 or type 2 cytokines) effectors from Clone
4 TCR-transgenic mice, which were adoptively transferred into syngeneic adult
thymectomized irradiated and bone marrow-reconstituted recipients. The highly
activated blast-size, CD25+ Tc1 and Tc2 effectors gave rise to homogeneous
resting CD25- CD44(high) Ly6C(high) Ag-specific populations, which persisted for
at least 13 wk after adoptive transfer. These memory CD8 T cells, recovered 13 wk
after transfer of Tc1 or Tc2 effectors, still produced either the type 1 or type
2 cytokines, i.e., IFN-gamma, or IL-4 and IL-5, respectively, upon restimulation
with APCs loaded with the HA peptide, but not in the absence of Ag. The amounts
of IL-2 detected in the supernatants of Tc1 and Tc2 memory populations were
comparable to that in memory CD4 cells, and both Tc1 and Tc2 memory cells became
cytotoxic upon restimulation. Thus, cytokine-polarized CD8 memory T cells are a
source of a variety of cytokines, which were classically considered helper
cytokines, opening new perspectives on their function as regulatory cells in an
immune response.
PMID- 9647213
TI - TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs.
AB - Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)
derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively.
Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell
responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross
reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides
were not. Surprisingly, despite the cross-reactivity of the responses, when Ig
PLP1 and Ig-PLP-LR were administered together into mice, a dose-dependent down
regulation of both T cell responses and a reduction of IL-2 production to
background levels was observed. In contrast, when T cells induced by either Ig
chimera were stimulated in vitro with mixtures of free PLP1 and PLP-LR peptides,
there was no down-regulation of proliferation or decrease in IL-2 production.
These data indicate that Ig-PLP1 and Ig-PLP-LR exert adverse reactions on one
another at the level of naive T cells, resulting in an opposite antagonism.
However, naive T cells experiencing either chimera develop into cross-reactive
cells, acquire resistance to TCR triggering by closely related but different
peptides, and support responsiveness.
PMID- 9647214
TI - Proteasomes can either generate or destroy MHC class I epitopes: evidence for
nonproteasomal epitope generation in the cytosol.
AB - Proteasomes have been implicated in the production of the majority of peptides
that associate with MHC class I molecules. We used two different proteasome
inhibitors, the peptide aldehyde N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL)
and the highly specific inhibitor lactacystin, to examine the role of proteasomes
in generating peptide epitopes associated with HLA-A*0201. Neither LLnL nor
lactacystin was able to completely block the expression of the HLA-A*0201.
Furthermore, the effects of LLnL and lactacystin on the expression of different
categories of specific epitopes, TAP independent vs TAP dependent and derived
from either cytosolic or membrane proteins, were assessed. As predicted,
presentation of two TAP-dependent epitopes was blocked by LLnL and lactacystin,
while a TAP-independent epitope that is processed in the endoplasmic reticulum
was unaffected by either inhibitor. Surprisingly, both LLnL and lactacystin
increased rather than inhibited the expression of a cytosolically transcribed and
TAP-dependent peptide from the influenza A virus M1 protein. Mass spectrometric
analyses of in vitro proteasome digests of a synthetic 24 mer containing this
epitope revealed no digestion products of any length that included the intact
epitope. Instead, the major species resulted from cleavage sites within the
epitope. Although cleavage at these sites was inhibitable by LLnL and
lactacystin, epitope-containing species were still not produced. We conclude that
proteasomes may in some cases actually destroy epitopes that would otherwise be
destined for presentation by class I molecules. These results suggest that some
epitopes are generated by nonproteasomal proteases in the cytosol.
PMID- 9647215
TI - Endogenous IL-12 is required for induction and expression of experimental
autoimmune uveitis.
AB - Experimental autoimmune uveitis (EAU) has been associated with a Th1 response.
However, in IFN-gamma-deficient mice, EAU develops in the context of an effector
response having Th2-like elements, and administration of IL-12 to mice immunized
for EAU induction can be protective. We, therefore, investigated whether
endogenous IL-12 is required for development of EAU. IL-12 p40-deficient mice
(12KO) were resistant to EAU induced with the uveitogenic retinal Ag
interphotoreceptor retinoid binding protein (IRBP). Delayed hypersensitivity to
IRBP was marginally reduced, whereas Ag-specific proliferation was enhanced.
Primed lymphocytes of wild-type (wt) mice, cultured with IRBP, produced a Th1
like cytokine profile and transferred EAU to syngeneic wt recipients.
Interestingly, the same cells were inefficient in transferring EAU to 12KO
recipients, unless IL-12 was included in the culture. Primed cells of the 12KO
mice produced a Th2-like cytokine profile and failed to transfer EAU. However,
when IL-12 was added to the culture, 12KO cells produced large amounts of IFN
gamma and transferred EAU to naive 12KO recipients. We conclude that resistance
to EAU of 12KO mice is not due to an inherent inability of these mice to develop
ocular disease. Despite an apparent similarity in Ag-specific cytokine responses
to IFN-gamma-deficient mice, 12KO mice have inhibited generation of uveitogenic
effector cells, a situation that can be reversed even after priming, by adding
exogenous IL-12 ex vivo. Lastly, the diminished ability of primed wt lymphocytes
to induce EAU in 12KO mice indicates a role for endogenous IL-12 in the efferent
phase of disease expression that is distinct from its role during Ag priming.
PMID- 9647216
TI - In vivo expression of a TCR antagonist: T cells escape central tolerance but are
antagonized in the periphery.
AB - Transgenic 3.L2 T cells are stimulated by Hb(64-76)/I-Ek and are positively
selected on I-Ek plus self-peptides. To this pool of self-peptides we have added
a single, well-defined 3.L2 TCR antagonist (A72) in vivo. We find that mice
expressing both the 3.L2 TCR and A72 have a minimal loss of T cells expressing
the clonotypic TCR in the thymus and spleen. Importantly, the proliferative
response of 3.L2 x A72 splenocytes is significantly reduced compared with
splenocytes from 3.L2 mice. This reduced response can be attributed to peripheral
antagonism. Thus we have identified a new class of self-ligands whose predominant
effect is constitutive peripheral antagonism rather than negative selection. The
net effect of these ligands is to avoid potential self-reactivity while
maintaining as large a repertoire as possible.
PMID- 9647217
TI - Characterization of human fibroleukin, a fibrinogen-like protein secreted by T
lymphocytes.
AB - We have recently cloned the human homologue of the murine pT49 cDNA (hpT49h), a
transcript encoding a protein homologous to the beta- and gamma-chains of
fibrinogen. Here, we report the identification of the hpT49h gene product using
mAbs generated against a peptide corresponding to the carboxyl-terminal end of
the deduced protein and a recombinant protein fragment expressed in Escherichia
coli. mAbs 23A6, 7B12, and 3F4 specifically recognized a protein of 70 kDa in
reducing SDS-PAGE in the culture supernatant of 293T cells transiently
transfected with the full length hpT49h cDNA and freshly isolated PBMC. Under
nonreducing conditions, the material migrated with a molecular mass of 250 to 300
kDa, indicating that the 70-kDa protein forms a disulfide bonded complex. Because
of its homology with fibrinogen, we have termed this protein fibroleukin.
Fibroleukin is spontaneously secreted in vitro by freshly isolated CD4+ and CD8+
T lymphocytes. RT-PCR analysis revealed preferential expression of fibroleukin
mRNA in memory T lymphocytes (CD3+/CD45R0+) compared with naive T lymphocytes
(CD3+/CD45RA+). Fibroleukin production by PBMC was rapidly lost in culture.
Production could be partially maintained in the presence of IFN-gamma, while T
lymphocyte activation had no effect. To demonstrate fibroleukin production in
vivo, we analyzed colon mucosa by immunohistology. Fibroleukin staining was
detected in the extracellular matrix of the T lymphocyte-rich upper portion of
the lamina propria mucosa. While the exact function of fibroleukin remains to be
defined, these data suggest that fibroleukin may play a role in physiologic
lymphocyte functions at mucosal sites.
PMID- 9647218
TI - Strong alloantigenicity of the alpha-helices residues of the MHC class I
molecule.
AB - To evaluate the role of single residues of a MHC class I molecule in the
induction of a primary allogeneic response, we have tested the ability of various
point mutants (of the alpha-helices or beta-sheet of the alpha1 and alpha2
domains) of the Kd molecule to induce a primary cytotoxic T cell response in mice
carrying the wild-type molecule. For that, we have used an in vivo model in which
cells expressing mutant molecules were injected into the hind footpads of mice
carrying wild-type Kd, and the recipient graft-draining popliteal lymph nodes
were tested for the presence of alloreactive CTL. Under these experimental
conditions, only 7 of the 25 mutant Kd molecules induced a primary allogeneic
response. All of these mutations (positions 62, 65, 69, 72, 155, 163, 166)
concern residues of the alpha-helices, demonstrating that very small variances
from self in a class I molecule, located outside the peptide-binding groove, can
be antigenic. To determine the peptide requirements for the generation of a
primary allogeneic response, we have analyzed the repertoire of peptides selected
by individual mutant molecules shown to be able or unable to induce a CTL
response. No correlation was observed between the peptidic make-up presented by a
given mutant and its capacity to induce a primary allogeneic response. On the
whole, our data point to the alloantigenicity of potentially TCR-contacting
surface residues of the MHC class I molecules.
PMID- 9647219
TI - Induction of oral tolerance in TGF-beta 1 null mice.
AB - Previous studies have suggested that oral tolerance induction by low doses of Ag
is mediated by inhibitory cytokines, particularly TGF-beta 1. To examine the
roles of TGF-beta 1 and other inhibitory cytokines in the induction of oral
tolerance, TGF-beta 1 null mice and controls were gavaged with 10 to 20 mg (high
dose) or 1 mg (low dose) of OVA for 3 days. After immunization with OVA, the in
vitro proliferative response of OVA-specific popliteal lymph node cells was
assessed. Lymphocytes from all TGF-beta 1 null mice fed high doses of OVA
exhibited highly significant suppression compared with controls. A weaker, but
still significant, suppression was observed in lymphocytes from the majority of
TGF-beta 1 null mice fed low doses of OVA. In addition, supernatants from these
lymphocytes exhibited lower levels of IL-4, IL-10, and IFN-gamma than those from
water-fed control animals. These results indicate that while TGF-beta 1 may play
a role in suppression, inhibitory cytokines are not the exclusive mechanism by
which low dose oral tolerance is induced.
PMID- 9647220
TI - A role for heat shock protein 27 in CTL-mediated cell death.
AB - CTL exocytosis of granules containing perforin and granzyme proteases induces
apoptotic cell death. Either granzyme A or B can act with perforin to trigger
apoptosis. Granzyme B activates a ubiquitous apoptotic cascade induced by caspase
cleavage, but the granzyme A pathway is largely unknown. Using affinity
chromatography with recombinant mutant inactive granzyme A, we previously
isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein)
I and II. PHAP II, a substrate of granzyme A, is degraded within minutes of CTL
attack. Two additional cytoplasmic proteins of 27 and 53 kDa bind strongly to the
mutant granzyme A column, requiring 6 M urea to elute. Sequencing identified
these as the monomer and dimer of hsp27, a small heat shock protein up-regulated
by stress and cellular activation. Hsp27 coprecipitates with granzyme A from
cytoplasmic lysates and is not a substrate of the enzyme. Hsp27 translocates to
the detergent-insoluble fraction of target cells and relocalizes from diffuse
cytoplasmic staining to long filamentous fibers, especially concentrated in a
perinuclear region, within minutes of CTL attack. Hsp27 may participate in
morphologic changes during granule-mediated lysis. Low or absent levels of hsp27
expression in T lymphocytes, even after heat shock, may play a role in CTL
resistance to granule-mediated lysis.
PMID- 9647221
TI - A comparison of signaling requirements for apoptosis of human B lymphocytes
induced by the B cell receptor and CD95/Fas.
AB - To define how the signaling pathways that mediate the B cell receptor (BCR) death
pathway differ from those responsible for CD95/Fas-mediated death, we compared
the BCR and Fas death pathways in two human B cell lines, B104 and BJAB. Both BCR
and Fas-induced apoptosis are blocked by the peptide cysteine protease inhibitor
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD (mlz)), demonstrating a
common requirement caspase activity. Despite this common characteristic, the
ability of actinomycin D and cycloheximide to block BCR-induced apoptosis, but
not apoptosis induced by Fas cross-linking, suggests that a major difference
between these two pathways is their differential requirements for new gene and
protein synthesis. BCR- and Fas-mediated apoptosis are both accompanied by
activation of stress-activated protein kinase and p38 mitogen-activated protein
kinase (MAPK). Activation of both stress-activated protein kinase and p38 MAPK
was inhibited by ZVAD (mlz), suggesting the involvement of caspases. To determine
the role of p38 MAPK activation in BCR- and Fas-induced apoptosis, we employed
SB203580, a specific inhibitor of p38 MAPK. SB203580 inhibited BCR-induced
apoptosis, but not apoptosis induced by cross-linking Fas. Furthermore, both
actinomycin D and SB203580 inhibited BCR-induced, but not Fas-induced, activation
of caspase. Collectively, these findings establish a role for p38 MAPK in BCR
induced apoptosis both upstream and downstream of caspase activity. The p38 MAPK
pathway may function to regulate transcriptional or translational events that are
critical for BCR-induced apoptosis.
PMID- 9647222
TI - CD4+ T cells mature in the absence of MHC class I and class II expression in Ly
6A.2 transgenic mice.
AB - The TCRs expressed on T lymphocytes recognize foreign peptides bound to MHC
molecules. This reactivity is the basis of specific immune response to the
foreign Ag. How such specificities are generated in the thymus is still being
debated. Signals generated through TCR upon interaction with self MHC-peptide
complexes are critical for maturation of the CD4+ helper and CD8+ cytotoxic
subsets. We have observed maturation of CD4+ but not CD8+ T cells in Ly-6A.2
transgenic MHC null mice. Since there can be no interactions with MHC molecules
in these mice, these CD4+ cells must express the T cell repertoire that exists
before positive and negative selection. Interestingly, despite an absence of
selection by MHC molecules, the CD4+ cells that mature recognize MHC molecules at
a frequency as high as in CD4+ cells in normal mice. These results demonstrate
that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC
molecules; and 2) CD4+ cells as opposed to CD8+ cells have distinct lineage
commitment signals. These results also suggest that signals originating from Ly-6
can promote or substitute for signals generated from TCR that are required for
positive selection. Moreover, this animal model offers a system to study T cell
development in the thymus that can provide insights into mechanisms of lineage
commitment in developing T cells.
PMID- 9647223
TI - The cytoplasmic domain of CD8 beta regulates Lck kinase activation and CD8 T cell
development.
AB - Previous studies have shown that CD8 beta plays a role in both enhancing CD8
alpha-associated Lck kinase activity and promoting the development of CD8-lineage
T cells. To examine the role of this enhancement in the maturation of CD8-lineage
cells, we assessed CD8 alpha-associated Lck kinase activity in both T cell
hybridomas and thymocytes of mice expressing CD8 beta mutations known to impair
CD8 T cell development. Lack of CD8 beta expression or expression of a
cytoplasmic domain-deleted CD8 beta resulted in a severalfold reduction in CD8
alpha-associated Lck kinase activity compared with that observed with cells
expressing wild-type CD8 beta chain. This analysis indicated a critical role for
the cytoplasmic domain of CD8 beta in the regulation of CD8 alpha-associated Lck
activity. Decreased CD8 alpha-associated Lck activity observed with the various
CD8 beta mutations also correlated with diminished in vivo cellular tyrosine
phosphorylation. In addition, analysis of CD8 beta mutant mice (CD8 beta-/- or
cytoplasmic domain-deleted CD8 beta transgenic) indicated that the degree of
reduction in CD8 alpha-associated Lck activity associated with each mutation
correlated with the severity of developmental impairment. These results support
the importance of CD8 beta-mediated enhancement of CD8 alpha-associated Lck
kinase activity in the differentiation of CD8 single-positive thymocytes.
PMID- 9647224
TI - Tissue-specific up-regulation of B7-1 expression and function during the course
of murine relapsing experimental autoimmune encephalomyelitis.
AB - B7/CD28-mediated costimulation is a promising target for therapeutic intervention
in autoimmune diseases. However, studies addressing the differential functional
roles of B7-1 and B7-2 in several autoimmune models have resulted in conflicting
data, perhaps due to the temporal dynamics of B7-1 and B7-2 surface expression on
different cell types and/or at different sites during an autoimmune response. We
examined the temporal expression of B7 costimulatory molecules in the CNS and in
various lymphoid organs during the course of murine relapsing-remitting
experimental autoimmune encephalomyelitis (R-EAE). Following immunization of SJL
mice with the immunodominant proteolipid protein epitope, PLP139-151, surface
expression of B7-1 was up-regulated on B cells, T cells, and macrophages,
relative to B7-2, on CNS-infiltrating cells and on splenocytes. Similar
enhancement in splenic B7-1 expression could be induced in SJL mice by the
adoptive transfer of PLP139-151-specific cells or by immunization with CFA alone.
These changes were not observed on lymph node cells, including those isolated
from lymph nodes draining the immunization site, which maintained the predominant
B7-2 expression pattern seen in naive mice. These phenotypic expression patterns
correlated with the functional predominance of B7-1 in costimulating T cell
activation when employing APCs from the spleen or CNS of mice with ongoing R-EAE,
while B7-2 remained functionally predominant on lymph node APCs. Variation of
phenotypic expression and functional dominance of costimulatory molecule
expression in different lymphoid compartments during an active inflammatory
autoimmune response has important implications in immune regulation, autoimmune
pathogenesis, and therapeutic strategies.
PMID- 9647225
TI - A partially modified retro-inverso pseudopeptide modulates the cytokine profile
of CTL specific for an influenza virus epitope.
AB - There is considerable evidence that peptides corresponding to MHC class I
restricted epitopes can be used as immunogens or immunomodulators. Pseudopeptides
containing isosteric replacements of the amide bond provide more stable
analogues, which may even have enhanced biologic activity. But there have been
very few studies on the use of pseudopeptides to initiate or modulate the
cellular immune response. This study describes the immunogenicity of a partially
modified retro-inverso pseudopeptide of an influenza virus epitope and shows that
this pseudopeptide modulates the cytokine profile expressed by CD8+ CTL generated
from primed precursors. Moreover, the pseudopeptide is much more efficient at low
concentration than the wild-type epitope to stimulate IFN-gamma secretion by CD8+
T effector cells. These results are analyzed with reference to changes in the
conformation of the MHC molecule/peptide complex deduced from molecular modeling.
The findings support the idea that partially modified retro-inverso analogues can
be used as altered peptide ligands to enhance the stimulation of natural epitope
specific CTL and to modify their functional properties. Hence, pseudopeptide
ligands might be promising tools for use in immunotherapy.
PMID- 9647226
TI - V7 (CD101) ligation inhibits TCR/CD3-induced IL-2 production by blocking Ca2+
flux and nuclear factor of activated T cell nuclear translocation.
AB - Ligation of the V7 (CD101) molecule on T cells with anti-V7 mAb blocks TCR/CD3
induced proliferation by inhibiting IL-2 transcription. To explore the basis for
this observation, we analyzed the effects of V7 ligation on CD3/TCR-induced
changes in intracellular free Ca2+ and Ca2+-dependent nuclear factor of activated
T cells (NF-AT) translocation to the nucleus, which is required for IL-2
transcription. T cells exposed to anti-V7 mAb fluxed Ca2+ transiently, but did
not flux Ca2+ in response to subsequent treatment with anti-CD3; however, they
recovered the capacity to flux Ca2+ after treatment with pervanadate, indicating
that tyrosine dephosphorylation of a critical V7-related substrate is required in
the desensitization process. One such substrate, phospholipase C (PLC)-gamma1,
becomes tyrosine phosphorylated on CD3/TCR activation and mediates inositol
triphosphate-dependent Ca2+ flux. Co-cross-linking of T cells with anti-CD3 and
anti-V7 resulted in selective inhibition of PLC-gamma1 tyrosine phosphorylation,
which may explain V7-mediated blockade of anti-CD3-induced Ca2+ flux. Moreover,
anti-CD3-induced binding of transcription factors to a consensus NF-AT-binding
oligonucleotide, which is dependent on Ca2+, was blocked completely by treatment
of the cells with anti-V7, whereas binding to a consensus-activating protein-1
oligonucleotide was unaffected. Western blot analysis of cytoplasmic and nuclear
extracts confirmed that anti-V7 prevented nuclear translocation of NF-ATc induced
by anti-CD3. We conclude that V7 ligation interferes with T cell activation and
IL-2 secretion through a Ca2+ and tyrosine kinase-dependent pathway that inhibits
PLC-gamma1 phosphorylation and prevents NF-AT translocation to the nucleus.
PMID- 9647227
TI - Differential regulation of the Janus kinase-STAT pathway and biologic function of
IL-13 in primary human NK and T cells: a comparative study with IL-4.
AB - IL-13, a cytokine similar to IL-4, is a regulator of human B cell and monocyte
functions. Biologic effects of IL-13 on primary human NK and T cells have not
been well defined. We demonstrate that, in primary NK cells, IL-13, but not IL-4,
may induce low levels of IFN-gamma secretion. When NK cells were costimulated
with IL-13 and IL-2, IL-13 generally resulted in two types of reactivity: IL-13
synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited
IL-2-mediated IFN-gamma production. In both types of donors, the effect of IL-13
on IL-2-induced IFN-gamma production was in marked contrast to the strong
inhibition seen with IL-4 in NK cells. Additionally, IL-13 suppresses IL-2
induced NK cytolytic and proliferative activities although less efficiently than
IL-4. In T cells, IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma
production and enhances cytolytic potential. Furthermore, we demonstrate that IL
13, like IL-4, induces distinct STAT6-DNA binding complexes and tyrosine
phosphorylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells. We observed
that Abs directed against unique domains of STAT6 have differential effects on
complexes in T cells but not in NK cells, suggesting different STAT6 isoforms.
These findings show that IL-13 and IL-4 have the ability to regulate NK and T
cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these
cell types.
PMID- 9647228
TI - Development of human peripheral TCRBJ gene repertoire.
AB - Previous studies of TCRBJ gene repertoires of human peripheral T lymphocytes
showed that all TCRBV family transcripts had some common features in BJ gene
usage, and nevertheless, transcripts of each BV family gene had a distinct
pattern. To discern how the development of the peripheral BJ repertoire is
controlled, the effects of preferential BJ gene rearrangement, thymic selection,
and peripheral stimulation on the repertoire formation were investigated. A PCR
ELISA technique was used to examine the immature CD3- CD4+ CD8-, and mature CD3+
CD4+ CD8- and CD3+ CD4- CD8+ thymocytes, and peripheral CD4+ and CD8+ T
lymphocytes for their BJ gene repertoires. Analogous to the peripheral
repertoire, the BJ gene repertoires of the immature thymocytes displayed common
features, and each BV transcript had a distinct pattern. All features were
conserved well by those of mature thymocytes and peripheral T lymphocytes. In
addition, the BJ gene repertoires of mature CD4 and CD8 thymocytes and peripheral
lymphocytes with the same coreceptors were apparently different in a few BV-BJ
combinations. The results showed that the overall BJ gene repertoire pattern was
developed before antigenic selection. Thus, the preferential BJ gene expression,
primarily based on preferential use of certain BJ gene rearrangements, dictates
the peripheral BJ gene repertoire, which is then further modified by thymic
selection and peripheral stimulation.
PMID- 9647229
TI - The prototypic Th2 autoimmunity induced by mercury is dependent on IFN-gamma and
not Th1/Th2 imbalance.
AB - Imbalances of Th1- and Th2-type responses have been postulated to be a
predisposing factor for both humoral and cellular mediated autoimmune diseases.
To further define their roles in systemic autoimmunity, IL-4 and IFN-gamma gene
knockout mice were studied for susceptibility to the prototypic Th2-mediated
mercury-induced autoimmunity. A predominant Th2-type response following HgCl2
treatment of wild-type B10.S mice was confirmed by the findings of a significant
increase in splenic IL-4 and hypergammaglobulinemia primarily of the IgG1
isotype, without an increase in IFN-gamma levels. Paradoxically, IL-4-deficient
mice developed the characteristic anti-nucleolar autoantibodies and tissue
deposition of immune complexes, while IFN-gamma-deficient mice had very low
autoantibody levels and essentially normal immunohistology. Studies to define
defects in Ab responses of IFN-gamma-deficient mice, using the T-dependent Ag (4
hydroxy-3-nitrophenyl)acetyl, revealed an attenuated IgG response to low and to a
lesser extent high doses of (4-hydroxy-3-nitrophenyl)acetyl-hemocyanin, but
maintenance of affinity maturation. These results indicate that Th1/Th2 imbalance
does not directly play a role in susceptibility to mercury-induced autoimmunity,
and suggest that the dependence on Th1-type responses in certain autoimmune
diseases is due to the requirement for IFN-gamma for Ab production to weakly
antigenic self molecules.
PMID- 9647230
TI - Fas/Fas ligand interactions are involved in ultraviolet-B-induced human
lymphocyte apoptosis.
AB - We wondered whether the apoptosis known to occur after UV-B irradiation might
involve the Fas/Fas ligand (FasL) signaling pathway. We exposed PBLs from normal
individuals, and also the Jurkat (E6-1) and U937 cell lines, to graded doses of
UV-B irradiation and observed a prompt and marked increase in Fas expression at
doses as low as 0.5 mJ/cm2. Increased Fas expression did not require new protein
synthesis, since cycloheximide-treated cells also showed an increase in Fas after
UV-B. UV-B-irradiated cells cultured in the presence of zinc showed inhibition of
apoptosis coincident with a marked increase in Fas+ cells, apparently indicating
the accumulation of Fas-bearing cells unable to undergo apoptosis. After UV-B
irradiation, PBLs showed increased expression of Fas ligand; the E6-1 lymphocytic
cell line also released soluble FasL. UV-B induced apoptosis could be partially
blocked by neutralizing FasL Abs, and a FasL-resistant variant of E6-1 cell line
showed reduced apoptosis after UV-B irradiation, implying that the increase in
Fas expression signified a role for Fas in UV-induced apoptosis. UV-induced Fas
expression may serve to target stress-injured cells for removal by FasL-bearing
cells or by FasL produced by the cells themselves in response to the stimuli, and
may represent a general function of the Fas/FasL pathway in facilitating the
apoptosis and elimination of undesirable or harmful cells.
PMID- 9647231
TI - Role of mu heavy chain in B cell development. I. Blocked B cell maturation but
complete allelic exclusion in the absence of Ig alpha/beta.
AB - There is good evidence for a signaling role played by Ig heavy chain in the
developmental transition through the pre-B cell stage. We have previously
described signal-capable or signal-incapable mutants of mu heavy chain in which a
signaling defect is caused by failure to associate with the Ig alpha/beta
heterodimer. To further characterize the role of Ig heavy chain-mediated
signaling in vivo, as well as in B cell development and allelic exclusion, we
have created transgenic mice in which the B cells express these signal-capable
and signal-incapable mutant mu chains. Failure of mu to signal via Ig alpha/beta
results in a block in B cell development in mice expressing the signal-incapable
mu. A small number of B cells in these animals do escape the developmental block
and are expressed in the spleen and the periphery as B220+ transgenic IgM+ cells.
These cells respond to LPS by proliferating but show no response to T-independent
specific Ag. In contrast, B cells expressing the signal-capable B cell receptor
show a strong signaling response to Ag-specific stimulus. There is no Ig alpha
seen in association with signal-deficient IgM. Thus, the B cell receptor complex
is not assembled, and no signal can be delivered. Despite the block in
developmental signaling, allelic exclusion is complete. There is no detectable
coexpression of transgenic IgM and endogenous murine IgM, nor is there
rearrangement of the endogenous heavy chain genes. This suggests that differing
signaling mechanisms are responsible for the developmental transition and allelic
exclusion and thus allows for separate examination of these signaling mechanisms.
PMID- 9647232
TI - Two distinct pathways exist for down-regulation of the TCR.
AB - TCR down-regulation plays an important role in modulating T cell responses both
during T cell development and in mature T cells. Down-regulation of the TCR is
induced by engagement of the TCR by specific ligands and/or by activation of
protein kinase C (PKC). We report here that ligand- and PKC-induced TCR down
regulation is mediated by two distinct, independent mechanisms. Ligand-induced
TCR down-regulation is dependent on the protein tyrosine kinases p56(lck) and
p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based)
internalization motif. In contrast, PKC-induced TCR down-regulation is dependent
on the CD3gamma L-based internalization motif but independent of p56(lck) and
p59(fyn). Finally, our data indicate that in the absence of TCR ligation, TCR
expression levels can be finely regulated via the CD3gamma L-based motif by the
balance between PKC and serine/threonine protein phosphatase activities. Such a
TCR ligation-independent regulation of TCR expression levels could probably be
important in determining the activation threshold of T cells in their encounter
with APC.
PMID- 9647233
TI - Both PU.1 and nuclear factor-kappa B mediate lipopolysaccharide- induced HIV-1
long terminal repeat transcription in macrophages.
AB - We recently reported that LPS stimulation of monocytic cells leads to the
activation of PU.1, a member of the Ets family of transcription factors.
Phosphorylation of PU.1 by protein kinase CK2 was found to up-regulate its trans
activation function, but not its DNA binding activity. Previous studies suggested
that Ets proteins could bind to NF-kappa B motifs at the tetrameric core sequence
TTCC. In macrophages, LPS-inducible HIV-1 gene expression is mediated in part by
binding of NF-kappa B to identical tandem binding sites located within the long
terminal repeat (LTR). Thus, we performed additional studies to determine whether
PU.1 also played a role in regulating HIV-1 gene expression in macrophages. Our
functional studies revealed that activation of the HIV-1 LTR in LPS-stimulated
cells requires both NF-kappa B and PU.1. Extensive mutagenesis of the HIV-1 LTR
revealed that PU.1-dependent activation requires the Ets motif within the
upstream NF-kappa B site, whereas NF-kappa B itself binds to the downstream site.
We also found that insertion of five additional nucleotides between the NF-kappa
B sites abolished LPS inducibility, suggesting a direct interaction between
factors that bind these sites. Lastly, we found that mutation of PU.1 at serine
148, which prevents its phosphorylation by CK2, blocked its ability to activate
the HIV-1 LTR in response to LPS. These effects were promoter specific because
PU.1 did not affect LPS-inducible activation of a distinct NF-kappa B-dependent
promoter. While these data do not demonstrate direct binding of PU.1 to the HIV-1
LTR, they illustrate a novel role for PU.1 in activation of the HIV-1 LTR by LPS.
PMID- 9647234
TI - An NFAT-dependent enhancer is necessary for anti-IgM-mediated induction of murine
CD5 expression in primary splenic B cells.
AB - CD5 is a 67-kDa membrane glycoprotein the expression of which in murine splenic B
cells is induced by surface IgM cross-linking. To analyze this induction, we
transiently transfected primary splenic B cells with luciferase reporter
constructs driven by various wild-type and mutated CD5 5'-flanking sequences. The
transfected cells were subsequently cultured in medium with or without F(ab')2
anti-IgM (anti-IgM), and luciferase expression was assayed. Using this approach,
we identified a 122-bp enhancer element necessary for anti-IgM-mediated induction
of the CD5 promoter. Electrophoretic mobility shift assays indicated that four
inducible and four constitutive complexes form on the enhancer fragment in
nuclear extracts of primary B cells. Supershift assays revealed that two of the
inducible complexes contained NFATc. Point mutations that abolished NFAT binding
severely impaired enhancer function. Thus, CD5 is a target of NFAT in B cells. A
third inducible complex required an intact H4TF-1 site. One of several
constitutive complexes required an intact Ebox site while a second required an
intact putative ets binding site. Mutation of the H4TF-1, Ebox, and Ets sites, in
the presence of wild-type NFAT sites, significantly reduced the activity of the
enhancer. Therefore, the induction of B cell CD5 expression requires NFAT binding
and binding to at least one of three additional sites in the CD5 enhancer.
PMID- 9647235
TI - Crucial role of TCR gamma chain junctional region in prenyl pyrophosphate antigen
recognition by gamma delta T cells.
AB - Human gamma delta T cells recognize prenyl pyrophosphate Ags and their analogues
in a V gamma 2V delta 2 TCR-dependent manner. Few data are available regarding
the TCR structural requirements for recognition of such prenyl pyrophosphate Ags
by gamma delta T cells. Presently, we made chain pair switch, chimeric, and site
mutant gamma delta TCRs and transfected them into TCR- mutant Jurkat T cells to
examine the effects of changing the TCR gamma junctional region sequences on
reactivity to prenyl pyrophosphate Ags. Substitution of the TCR gamma junctional
region (N and J) sequences from an Ag-reactive TCR with TCR gamma junctional
region sequences from an Ag-nonreactive TCR abrogated reactivity to the prenyl
pyrophosphate Ag isopentenyl pyrophosphate and to its synthetic analogue ethyl
pyrophosphate but not to a mycobacterial supernatant containing a mixture of
prenyl pyrophosphate Ags. Substitution of only the TCR gamma N nucleotide region
with that from this Ag-nonreactive TCR destroyed reactivity to isopentenyl
pyrophosphate and to the mycobacterial supernatant. Substitution of the entire V
delta 2 chain from the Ag-reactive TCR with a V delta 1 chain from an Ag
nonreactive TCR yielded a prenyl pyrophosphate Ag-nonreactive TCR. Thus, using
TCR mutagenesis and TCR transfectants, we show that gamma delta TCR reactivity to
prenyl pyrophosphate Ags is dependent upon the junctional region of the TCR gamma
chain and upon pairing of V gamma 2 and V delta 2 TCR chains. These structural
requirements of TCR gamma delta recognition of prenyl pyrophosphates distinguish
this reactivity from that of protein superantigens and emphasize the importance
of the TCR gamma CDR3 loop and adjacent residues.
PMID- 9647236
TI - A lambda 3' enhancer drives active and untemplated somatic hypermutation of a
lambda 1 transgene.
AB - Somatic hypermutation is a highly regulated process that targets mutations to the
rearranged Ig genes. Little is known about the cis-elements required for somatic
hypermutation of the lambda light chain gene. We have studied somatic
hypermutation of a rearranged lambda 1 transgene under the control of either a
lambda 2-4 or kappa 3' enhancer. The mutations in the transgenes were analyzed by
sequencing DNA amplified from hypermutating Peyer's patch B cells. The results
indicate that the lambda 3' enhancer can drive active hypermutation of a lambda 1
transgene in Peyer's patch cells. The lambda 1 transgene under analysis carried
two marked V lambda 2 genes immediately upstream that could serve as sequence
donors in possible gene conversion events. There was no evidence of sequence
transfer to the hypermutated lambda 1 gene, suggesting that gene conversion is
not a major mechanism for somatic hypermutation in mice.
PMID- 9647237
TI - STAT6 is required for IL-4-induced germline Ig gene transcription and switch
recombination.
AB - Transcription of the germline C gamma1 and C epsilon Ig genes is believed to be a
necessary prerequisite for isotype switching to IgG1 and IgE, respectively. IL-4
stimulation and ligation of CD40 can each independently induce low level germline
gamma1 and epsilon transcription in murine B cells. Together these signals act
synergistically to promote high level germline transcription and are normally
required for T-dependent isotype switching to IgG1 and IgE. The STAT6
transcription factor has been suggested to play a critical role in IL-4-induced
activation of germline C gamma1 and C epsilon genes. To directly assess the role
of STAT6 in IL-4R- and CD40-mediated germline transcription and switching, we
have analyzed these events in splenic B cells from STAT6-deficient mice. Our
results demonstrate that IL-4 does not induce detectable levels of germline
gamma1 or epsilon transcripts in STAT6-deficient B cells. Germline transcript
expression induced by CD40 stimulation alone is unaffected, but synergism between
CD40- and IL-4R-mediated signals is completely ablated. Switch recombination to S
gamma1, as measured by digestion-circularization PCR, is dramatically reduced in
STAT6-deficient B cells stimulated with CD40 ligand plus IL-4. Similarly,
germline gamma1 transcript expression and switch recombination to S gamma1 are
also impaired in STAT6-deficient B cells stimulated with IL-4, IL-5, and anti-IgD
Abs conjugated to dextran, a model for T-independent type II responses. These
results directly demonstrate a critical role for STAT6 in the IL-4-mediated
activation of germline Ig gene transcription and switch recombination in
nontransformed B cells.
PMID- 9647238
TI - Expression and characterization of recombinant subunits of human complement
component C8: further analysis of the function of C8 alpha and C8 gamma.
AB - Human C8 is composed of three nonidentical subunits (C8 alpha, C8 beta, and C8
gamma) that are encoded in separate genes. In C8 isolated from serum, these are
arranged as a disulfide-linked C8 alpha-gamma dimer that is noncovalently
associated with C8 beta. In this study, a recombinant form of C8 alpha-gamma was
expressed independently of C8 beta in insect cells and COS-7 cells and was shown
to be equivalent to serum-derived C8 alpha-gamma with respect to its ability to
combine with C8 beta and form functional C8. Also expressed separately were
mutant (mut) forms of C8 alpha and C8 gamma in which the single interchain
disulfide bond was eliminated. MutC8 alpha exhibited the ability to combine with
C8 beta and express hemolytic activity, although at a lower level than human C8.
Addition of purified mutC8 gamma increased this activity, presumably by binding
to mutC8 alpha. A possible role for C8 gamma as a retinol binding protein was
also investigated. Absorbance spectroscopy and fluorescence emission and
quenching revealed no specific binding of retinol to mutC8 gamma. Together, these
results indicate that 1) the biosynthesis and secretion of C8 alpha-gamma is not
dependent on C8 beta, which is consistent with in vivo observations in C8 beta
deficient humans; 2) C8 alpha can be synthesized independently of C8 gamma;
therefore, protection of C8 alpha from premature membrane interactions during
biosynthetic processing is not a likely function of C8 gamma; 3) C8 gamma
enhances but is not required for expression of C8 activity; and 4) C8 gamma does
not bind retinol; therefore, it cannot function as a retinol transport protein.
PMID- 9647239
TI - The N-terminal domains target TNF receptor-associated factor-2 to the nucleus and
display transcriptional regulatory activity.
AB - The subcellular localization of the TNF receptor-associated factor-2 (TRAF2)
adaptor protein in human endothelial cells, which mediates proinflammatory
responses of TNF, has been analyzed by confocal immunofluorescence microscopy and
by Western blotting of fractionated cell extracts. Rabbit antisera reactive with
either amino- or carboxyl-terminal TRAF2 peptides frequently but not uniformly
stain nuclei of cultured HUVEC or the established human endothelial cell line,
ECV304. However, Western blotting reveals significant heterogeneity in the
reactivities of these polyclonal Abs. Transiently transfected HUVEC expressing
FLAG epitope-tagged TRAF2 consistently show prominent nuclear localization, and
deletion mutants of TRAF2 identify the portion of the molecule responsible for
nuclear localization as the amino-terminal ring finger domain. TNF treatment does
not appear to influence the localization of endogenous or transfected TRAF2
protein. Transfection of the amino-terminal half of the TRAF2 molecule,
containing the ring and zinc finger domains, which localizes to the nucleus,
results in activation of E-selectin but not of NF-kappaB promoter-reporter gene
transcription or of c-Jun N-terminal kinase activation. These observations
suggest that TRAF2 may reside in the nucleus and directly regulate transcription,
independent of its role in cytoplasmic signal transduction.
PMID- 9647240
TI - Regulation of IL-6 signaling by p53: STAT3- and STAT5-masking in p53-Val135
containing human hepatoma Hep3B cell lines.
AB - The influence of p53 on cytokine-triggered Janus kinase-STAT signaling was
investigated in human hepatoma Hep3B cell lines engineered to constitutively
express the temperature-sensitive Val135 mutant of p53. In comparison to the
parental p53-free Hep3B cells, these p53-Val135-containing Hep3B cell lines
displayed a reduced response to IL-6 at the wild-type-like p53 temperature (32.5
degrees C). In these cells, IL-6 induced a marked reduction in the immunologic
accessibility of cytoplasmic and nuclear STAT3 and STAT5 within 20 to 30 min that
lasted 2 to 4 h (STAT-masking) provided that the cells had been previously
cultured at 32.5 degrees C for at least 18 to 20 h. The onset of IL-6-induced
STAT-masking required protein tyrosine kinase, protein tyrosine phosphatase,
proteasomal, phospholipase C, and mitogen-activated protein kinase kinase 1
activities. The maintenance of IL-6-induced STAT-masking was dependent on
continued signaling through the phosphatidylinositol-dependent phospholipase C
pathway. Despite a reduction in IL-6-induced STAT3 DNA binding activity in the
nuclear compartment during STAT-masking, there was increased and prolonged
accumulation of tyrosine-phosphorylated STAT3 in both the cytoplasmic and nuclear
compartments, indicating that the capacity of tyrosine-phosphorylated STAT3 to
bind DNA was reduced during STAT-masking. Thus, IL-6-induced STAT-masking, as
dramatically evident on immunomicroscopy, is a visible consequence of a novel
cellular process by which a p53-Val135-induced gene product(s) regulates the
association of masking protein(s) with and the DNA-binding capacity of STAT3.
PMID- 9647241
TI - Differences between B cell and macrophage transformation by the bovine parasite,
Theileria annulata: a clonal approach.
AB - Theileria annulata, a tick-transmitted protozoan parasite, infects and transforms
cells of the hemopoietic system, particularly those of the B cell and
monocyte/macrophage lineages. Here, the effect of infection/transformation on the
resulting phenotype was studied using a clonal approach. Three phenotypes of
transformed cell lines could be discerned. The first is characterized by surface
expression of IgM, CD21, and the B cell epitopes, B-B2 and B-B8, Ig heavy chain
gene rearrangement, and mRNA expression. Such lines were obtained from fresh and
cultured PBMC and at increased frequency from purified B cells, but never from
fetal bone marrow cells. The second phenotype can be distinguished from the first
by the absence of Ig heavy chain expression and reduced surface expression of B
cell markers (CD21, B-B2, B-B8). Clones with this phenotype were obtained from
transformed fetal bone marrow cells only. The third phenotype showed an absence
of all of the above B cell markers, including surface IgM, and a lack of Ig heavy
chain gene rearrangement. The latter clones could be maintained for several weeks
after elimination of T. annulata by BW720c treatment, and they reacquired a
macrophage-like phenotype. This implies that parasite-induced dedifferentiation
is restricted to monocyte/macrophage, and that B cell markers are indicative of
cell lineage progeny. Demonstration of surface IgM on PBMC-derived B cell clones
suggests that infection of B cells with T. annulata may be an epigenetic method
to immortalize ruminant B cells of a defined Ag specificity.
PMID- 9647242
TI - Reduced tumorigenicity and augmented leukocyte infiltration after monocyte
chemotactic protein-3 (MCP-3) gene transfer: perivascular accumulation of
dendritic cells in peritumoral tissue and neutrophil recruitment within the
tumor.
AB - Monocyte chemotactic protein-3 (MCP-3) is a C-C chemokine that interacts with the
CCR1, CCR2, and CCR3 receptors and has a spectrum of action encompassing T cells,
NK cells, eosinophils, and dendritic cells (DC), in addition to mononuclear
phagocytes. This broad spectrum of action prompted the present study aimed at
assessing the antitumor activity of MCP-3 in a gene transfer approach and at
providing information as to the actual in vivo leukocyte recruiting capacity of
MCP-3. P815 mastocytoma cells transfected with the gene coding MCP-3 (P815/MCP-3)
grew in syngeneic hosts and underwent rejection. Rejection was associated with
profound alterations of leukocyte infiltration and resistance to subsequent
challenge with P815 cells. Tumor-associated macrophages, already present in
copious numbers, T cells, eosinophils, and neutrophils, increased in tumor
tissues after gene transfer. DC, identified as DEC205+, high MHC class II+,
CD11c+ cells, did not increase substantially in the tumor mass. However, in
peritumoral tissues, DC accumulated in perivascular areas. P815/MCP-3-transfected
tumor cells grew normally in nude mice. Increased accumulation of macrophages and
polymorphonuclear neutrophils was evident also in nude mice. mAb against CD4,
CD8, and IFN-gamma, but not against IL-4, inhibited rejection of MCP-3-producing
cells. An anti-polymorphonuclear mAb caused only a retardation of MCP-3-elicited
tumor rejection. Thus, MCP-3 gene transfer elicits tumor rejection by activating
type I T cell-dependent immunity. It is tempting to speculate that altered
trafficking of APCs, which express receptors and respond to MCP-3, together with
recruitment of activated T cells, underlies activation of specific immunity by
MCP-3-transfected cells.
PMID- 9647243
TI - A longitudinal study of type-specific antibody responses to Plasmodium falciparum
merozoite surface protein-1 in an area of unstable malaria in Sudan.
AB - Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine
candidate Ag. Immunity to MSP-1 has been implicated in protection against
infection in animal models. However, MSP-1 is a polymorphic protein and its
immune recognition by humans following infection is not well understood. We have
compared the immunogenicity of conserved and polymorphic regions of MSP-1, the
specificity of Ab responses to a polymorphic region of the Ag, and the duration
of these responses in Sudanese villagers intermittently exposed to P. falciparum
infections. Recombinant Ags representing the conserved N terminus (Block 1), the
conserved C terminus, and the three main types of the major polymorphic region
(Block 2) of MSP-1 were used to determine the specificity and longitudinal
patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were
assessed before, during, and after malaria transmission seasons for 4 yr. Ags
from the Block 1 region were rarely recognized by any donor. Responses to the C
terminal Ag occurred in the majority of acutely infected individuals and thus
were a reliable indicator of recent clinical infection. Ags from the polymorphic
Block 2 region of MSP-1 were recognized by many, although not all individuals
after clinical malaria infections. Responses to Block 2 were type specific and
correlated with PCR typing of parasites present at the time of infection.
Responses to all of these Ags declined within a few months of drug treatment and
parasite clearance, indicating that naturally induced human Ab responses to MSP-1
are short lived.
PMID- 9647244
TI - Susceptibility to Pneumocystis carinii in mice is dependent on simultaneous
deletion of IFN-gamma and type 1 and 2 TNF receptor genes.
AB - Pneumocystis carinii pneumonia is an important cause of morbidity and mortality
in immunosuppressed patients, particularly HIV-infected individuals. An improved
understanding of pulmonary host response, including the cytokines required for
defense, could suggest novel immunotherapeutic approaches to this infection. The
cytokines IFN-gamma and TNF have contributory roles in host defense against P.
carinii, but their combined and interactive importance is unclear. To test the
roles of these cytokines in defense against P. carinii directly, organisms were
inoculated intratracheally into wild-type mice and into three groups of gene
deleted mice: those lacking genes for IFN-gamma (IFN-gamma(-/-)), for TNF
receptors 1 and 2 (TNFR(-/-)), and for both IFN-gamma and TNFR (TNFR-IFN-gamma(-/
)). Four weeks after P. carinii inoculation, lungs of the wild-type, IFN-gamma(-/
), and TNFR(-/-) mice demonstrated clearance of P. carinii and only mild
inflammation. However, TNFR-IFN-gamma(-/-) mice demonstrated severe P. carinii
infection and lung inflammation. Our findings demonstrate conclusively that
deletion of either IFN-gamma or TNF activity alone does not block clearance of P.
carinii. However, simultaneous deletion of IFN-gamma and TNF receptor genes
results in susceptibility to P. carinii. Rather than focusing exclusively on
individual cytokines, our data suggest that immunotherapy targeted at maximizing
both the IFN-gamma and TNF responses to P. carinii may be required to augment
host defense against this important opportunistic pathogen.
PMID- 9647245
TI - Stability of virus-specific CD4+ T cell frequencies from acute infection into
long term memory.
AB - Mice infected with viruses develop long-lasting high frequency memory CD8+ T cell
pools, but much less is known about the CD4+ T cell response. FACS analysis
revealed the modulation of several activation markers on CD4+ T cells during an
acute infection with lymphocytic choriomeningitis virus (LCMV), consistent with
an activated cell phenotype. Examination of virus-specific cytokine production
using ELISPOT assays showed a significant increase in the number of IFN-gamma
secreting cells in the spleen during an acute LCMV infection. CD8+ T cells made
up the majority of the IFN-gamma-producing cells, but analysis of the cell
culture supernatants by ELISA showed that the CD4+ T cells produced more IFN
gamma on a per cell basis. Using limiting dilution assays, we examined the CD4+ T
cell precursor (Thp) frequency in C57BL/6 mice infected with LCMV. The virus
specific Thp frequency increased from <1/100,000 in uninfected mice to a peak of
approximately 1/600 in purified splenic CD4+ T cell populations by 10 days
postinfection with LCMV. After the peak of the response, the Thp frequency
decreased only about twofold per CD4+ T cell to approximately 1/1200 and remained
stable into long term memory. In contrast to the highly activated CD4+ T cells
recovered during the acute LCMV infection, the memory CD4+ T cells were
maintained at a lower activation state as judged by cell size and ability to
secrete IFN-gamma. Thus, like the CD8+ T cell frequencies, the CD4+ T cell
frequencies remain elevated after the acute infection subsides and stay elevated
throughout long term immunity.
PMID- 9647246
TI - Antigen-specific cytolysis by neutrophils and NK cells expressing chimeric immune
receptors bearing zeta or gamma signaling domains.
AB - TCR- and IgG-binding Fc receptors (Fc gamma R) mediate a variety of critical
biologic activities including cytolysis via the structurally related zeta- and
gamma-chains. In previous studies, we have described chimeric immune receptors
(CIR) in which the ligand-binding domain of a heterologous receptor or Ab is
fused directly to the cytoplasmic domain of the TCR zeta-chain. Such zeta-CIRs
efficiently trigger cytotoxic function of both T and NK cells in a target
specific manner. In this report, we compared the ability of both zeta- and gamma
CIRs to activate the cytolytic function of two distinct classes of Fc gamma R
bearing effectors, NK cells and neutrophils. Mature neutrophils expressing zeta-
and gamma-CIR were generated in vivo from murine hemopoietic stem cells following
transplantation of syngeneic mice with retrovirally transduced bone marrow or in
vitro from transduced human CD34+ progenitors following differentiation. Both
zeta- and gamma-based CIRs were capable of activating target-specific cytolysis
by both NK cells and neutrophils, although the zeta-CIR was consistently more
efficient. The experimental approach described is a powerful one with which to
study the role of nonlymphoid effector cells in the host immune system and
permits the rational design of immunotherapeutic strategies that rely on
harnessing multiple immune cell functions via CIR-modified hemopoietic stem cells
or progenitors.
PMID- 9647247
TI - Galectin-3 down-regulates IL-5 gene expression on different cell types.
AB - Galectin-3 is an animal lectin, formerly named epsilon-binding protein or Mac-2,
which has been described to play an important role in some inflammatory processes
by the implication of different cells and the increase in cell adhesion functions
through laminin binding activity. In this work we analyzed the role of galectin-3
in the modulation of Th2 cytokines that have an important role in the development
of the inflammatory response. We have found that the addition of galectin-3 to
human eosinophils, the eosinophilic cell line EoL-3, PBMC, and an Ag-specific T
cell line (CD4+) produced a selective inhibition of IL-5 transcription. No
inhibitory effect was found on the IL-4 mRNA transcription rate. The inhibitory
effect on IL-5 transcription was reversed by incubation with lactose and using
specific Ab against galectin-3. Galectin-3 is able to induce inhibition of the IL
5 released in the supernatants from PBMC stimulated with phorbol 12,13-dibutyrate
and anti-CD3. Similar results were obtained when a T-specific cell line was
stimulated with Ag. Also, EoL-3 stimulated with anti-CD32 produced IL-5 protein,
the synthesis of which was partially inhibited by galectin-3. The present results
demonstrate that galectin-3 induces a selective down-regulation of IL-5
expression in different cell types, opening important new possibilities in the
regulation of the allergic reactions.
PMID- 9647248
TI - Cooperation of both TNF receptors in inducing apoptosis: involvement of the TNF
receptor-associated factor binding domain of the TNF receptor 75.
AB - TNF-R55 is the main receptor mediating TNF-induced cytotoxicity. However, in some
cells TNF-R75 also signals cell death. In PC60 cells, the presence of both
receptor types is required to induce apoptosis following either specific TNF-R55
or TNF-R75 triggering, pointing to a mechanism of receptor cooperation. In this
study, we extend previous observations and show that TNF-R55 and TNF-R75
cooperation in the case of apoptosis in PC60 cells is bidirectional. We also
demonstrate ligand-independent TNF-R55-mediated cooperation in TNF-R75-induced
granulocyte/macrophage-CSF secretion, but not vice versa. To determine which part
of the intracellular TNF-R75 sequence was responsible for the observed receptor
cooperation in apoptosis, we introduced different TNF-R75 mutant constructs in
PC60 cells already expressing TNF-R55. Our data indicate that an intact TNF-R
associated factors 1 and 2 (TRAF1/TRAF2)-binding domain is required for receptor
cooperation. These findings suggest a role for the TRAF complex in TNF-R
cooperation in the induction of cell death in PC60 cells. Nevertheless,
introduction of a dominant negative (DN) TRAF2 molecule was not able to affect
receptor cooperation. Remarkably, TRAF2-DN overexpression, which was found to
inhibit the TNF-dependent recruitment of endogenous wild-type TRAF2 to the TNF
R75 signaling complex, could neither block TNF-R55- or TNF-R75-induced NF-kappaB
activation nor granulocyte/macrophage-CSF secretion. Possibly, additional factors
different from TRAF2 are involved in TNF-mediated NF-kappaB activation.
PMID- 9647249
TI - Differential expression and function of L-selectin on CD56bright and CD56dim
natural killer cell subsets.
AB - NK cells are the first line of defense against foreign cells, virally infected
cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid
sites in response to pathogenic stimuli are not well understood. The L-selectin
adhesion molecule (CD62L) plays a primary role in mediating the initial
interaction of leukocytes with vascular endothelium, a crucial step in the
extravasation of immune effector cells into tissues. In this report, we show L
selectin to be uniquely expressed on a subset of resting human NK cells
(CD56bright). Notably, CD56bright NK cells expressed L-selectin at a higher
density than all other peripheral blood leukocytes. NK activation by PMA, IL-2,
IL-15, or TGF-beta down-regulated L-selectin on the CD56bright subset, while
increased L-selectin levels were observed in both the CD56bright and CD56dim NK
subsets in response to IL-12, IL-10, or IFN-alpha. Moreover, CD56bright NK cells
bound with high efficiency to physiologic L-selectin ligands on peripheral lymph
node high endothelial venules (HEV). In sharp contrast, CD56dim NK cells adhered
poorly to HEV and were predominantly L-selectin- or expressed L-selectin only at
low density. In CD56bright cells and a subpopulation of CD56dim cells, L-selectin
ligation by mAb cross-linking activated lymphocyte function-associated Ag 1 (LFA
1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was
expressed on both NK subsets, although its density was constitutively higher on
CD56dim cells. Taken together, evidence of differential expression of L-selectin
and LFA-1 on CD56bright and CD56dim NK subsets strongly suggests unique migratory
properties and functions of these cells during the early immune response to
foreign pathogens.
PMID- 9647250
TI - Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor
production by rheumatoid arthritis synoviocytes and its regulation by Th2
cytokines.
AB - IL-17 is a cytokine produced by CD4 T cells that activates the production of
inflammatory mediators by synoviocytes. To study the contribution of soluble
factors in the interaction between T cells and synoviocytes in rheumatoid
arthritis (RA), we looked at the effect of IL-17 on these cells in the presence
of cytokines classified as pro (IL-1)- and anti-inflammatory (IL-4, IL-13, IL
10). Both human rIL-1beta and rIL-17 induced IL-6 and leukemia inhibitory factor
(LIF) production by synovial fibroblasts in a dose-dependent manner. After 7 days
of culture, optimal concentrations of IL-1beta increased IL-6 (33-fold) and LIF
(10-fold) production by synoviocytes, while IL-17 showed a lesser effect on IL-6
(17-fold) and LIF (4-fold) production. Using low concentrations of IL-17 and IL
1beta in combination, a synergistic effect was observed on the production of IL
6, whereas an additive effect was observed for LIF production. Production of
biologically active IL-17 was demonstrated in RA synovium supernatants with the
use of a blocking anti-IL-17 Ab. Both IL-4 and IL-13 had a modest stimulatory
effect on IL-1- and IL-17-induced production of IL-6, but inhibited that of LIF.
In contrast, IL-10 had a limited inhibitory effect on IL-6 production and no
effect on that of LIF. These findings indicate that low levels of cytokines
produced by monocytes (IL-1) and T cells (IL-17) can act together on
synoviocytes. Thus, some RA synovium T cells producing IL-17 can activate
mesenchymal cells leading to an increased proinflammatory pattern sensitive to
Th2 cytokine regulation.
PMID- 9647251
TI - Human eosinophils produce biologically active IL-12: implications for control of
T cell responses.
AB - The present study assessed the capacity of eosinophils (EOS) to synthesize the
cytokine IL-12. Blood-derived, highly purified human EOS from six atopic patients
and two nonatopic individuals were treated in culture with IL-4, IL-5,
granulocyte-macrophage CSF, IFN-gamma, TNF-alpha, IL-1alpha, RANTES, and
complement 5a, respectively. The expression of both IL-12 protein and mRNAs for
the p35 and p40 IL-12 subunits was strongly induced in all donors by the Th2-like
cytokines IL-4 and granulocyte-macrophage CSF and was also moderately induced by
TNF-alpha and IL-1alpha. IL-5 treatment resulted in IL-12 synthesis in four
atopic donors and one nonatopic donor, whereas IFN-gamma induced IL-12 synthesis
in only two atopic donors. In contrast, RANTES exclusively induced mRNA for the
p40 subunit without detectable protein release, and complement 5a had no effect
on IL-12 mRNA or protein expression. EOS-derived IL-12 was biologically active,
because supernatants derived from IL-4-treated EOS superinduced the Con A-induced
expression of IFN-gamma by a human Th1-like T cell line. This activity was
neutralized by anti-IL-12 Abs. In conclusion, EOS secrete biologically active IL
12 after treatment with selected cytokines, which mainly represent the Th2-like
type. Consequently, EOS may promote a switch from Th2-like to Th1-like immune
responses in atopic and parasitic diseases.
PMID- 9647253
TI - Angiotensin II participates in mononuclear cell recruitment in experimental
immune complex nephritis through nuclear factor-kappa B activation and monocyte
chemoattractant protein-1 synthesis.
AB - Angiotensin-converting enzyme (ACE) inhibitors reduce macrophage infiltration in
several models of renal injury. We approached the hypothesis that angiotensin II
(AngII) could be involved in inflammatory cell recruitment during renal damage
through the synthesis of monocyte chemoattractant protein-1 (MCP-1). In a model
of immune complex nephritis, we observed an up-regulation of renal MCP-1 (mRNA
and protein) coincidentally with mononuclear cell infiltration that were markedly
reduced by treatment with the ACE inhibitor quinapril. Exposure of cultured rat
mesangial cells to AngII increased MCP-1 mRNA expression (2.7-fold) and synthesis
(3-fold), similar to that observed with TNF-alpha. Since NF-kappaB is involved in
the regulation of MCP-1 gene, we explored whether the effects of AngII were
mediated through NF-kappaB activation. Untreated nephritic rats showed increased
renal NF-kappaB activity (3.5-fold) that decreased in response to ACE inhibition.
In mesangial cells, AngII activated NF-kappaB (4.3-fold), and the NF-kappaB
inhibitor pyrrolidine dithiocarbamate abolished the AngII-induced NF-kappaB
activation and MCP-1 gene expression. Our results suggest that AngII could
participate in the recruitment of mononuclear cells through NF-kappaB activation
and MCP-1 expression by renal cells. This could be a novel mechanism that might
further explain the beneficial effects of ACE inhibitors in progressive renal
diseases.
PMID- 9647252
TI - A synthetic CD4-CDR3 peptide analog enhances skin allograft survival across a MHC
class II barrier.
AB - The efficacy of a synthetic peptide analogue (rD-mPGPtide), mimicking the CDR3
region in the first domain of the CD4 surface molecule, was investigated in a
murine model for CD4+ T cell-mediated skin allograft rejection. A single
injection of rD-mPGPtide shortly before transplantation exhibited significantly
prolonged graft survival in the B6 anti-B6.C-H2bm12 MHC class II-disparate strain
combination. Long-term graft survival (>100 days) was achieved when thymectomized
adult recipient mice were transplanted along with rD-mPGPtide treatment. The
peptide also affected secondary rechallenge responses with MHC class II
allografts. In addition, the inhibitory effect of the rD-mPGPtide in this
transplantation model was directed against CD4+ T cells and was exclusively
specific toward donor alloantigen. In vitro analysis of CD4+ T cells isolated
from the draining lymph nodes of rD-mPGPtide-treated recipients indicated a 450
fold decrease in precursor frequency in response to donor allostimulation
compared with the untreated control group. There was also significant down
regulation of the frequency of IL-2-, IFN-gamma-, and IL-4-producing CD4+ T cells
upon in vitro allogeneic restimulation of host cells 4 days posttransplantation.
However, these same CD4+ T cells maintained the capacity to produce normal
cytokine levels upon third-party allostimulation. Thus, these studies demonstrate
that a CD4-CDR3 peptide analogue can specifically and effectively prolong skin
graft survival across MHC class II barriers.
PMID- 9647254
TI - Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil
chemoattractant in the lung: role in pulmonary inflammation following
lipopolysaccharide.
AB - Recent studies have suggested that hemorrhagic shock followed by resuscitation
renders patients more susceptible to lung injury by priming for an exaggerated
response to a second stimulus, the so-called "two-hit" hypothesis. We
investigated the role of C-X-C chemokines in mediating the augmented lung
inflammation in response to LPS following resuscitated shock. In a rodent model,
animals exposed to antecedent shock exhibited enhanced lung neutrophil
sequestration and transpulmonary albumin flux in response to intratracheal LPS.
This effect correlated with an exaggerated expression of cytokine-induced
neutrophil chemoattractant (CINC) protein and mRNA, but not macrophage
inflammatory protein 2. Strategies designed to inhibit CINC, both anti-CINC Ab
and supplementation with the antioxidant N-acetyl-cysteine, prevented the
enhanced neutrophil sequestration, suggesting that CINC played a central role in
the enhanced leukocyte accumulation following shock plus LPS treatment. Shock
alone increased lung nuclear factor-kappaB expression and augmented the response
to LPS. Prevention of this effect by N-acetylcysteine supplementation of the
resuscitation fluid implicates a role for oxidant stress in the priming for lung
inflammation following shock. Finally, alveolar macrophages recovered from shock
resuscitated animals released more CINC protein in vitro in response to LPS than
macrophages from sham animals. Considered together, these findings show that
augmented release of CINC, in part from primed alveolar macrophages, contributes
significantly to the enhanced lung leukosequestration and transpulmonary albumin
flux in response to LPS following resuscitated shock.
PMID- 9647255
TI - T cell epitopes in Japanese cedar (Cryptomeria japonica) pollen allergens: choice
of major T cell epitopes in Cry j 1 and Cry j 2 toward design of the peptide
based immunotherapeutics for the management of Japanese cedar pollinosis.
AB - Japanese cedar pollinosis is caused by exposure to Japanese cedar (Cryptomeria
japonica) pollen, of which two components, Cry j 1 and Cry j 2, are believed to
be the major allergens. T cell lines specific to either Cry j 1 or rCry j 2 were
reactive to various portions of each panel of overlapping peptides derived from
Cry j 1 or Cry j 2. Two peptides, p211-225 and p108-120, from among six major T
cell epitopes identified in Cry j 1 sequence, and three peptides, p182-200, p344
355, and p66-80, from among five in Cry j 2, were chosen to design an artificial
polypeptide (named Cry-consensus) based on a difference among the types of the
restriction molecules capable of presenting these peptides. After construction of
a DNA encoding these peptides in order, Cry-consensus was expressed in
Escherichia coli. Five of six T cell epitopes, except for Cry j 2 p344-355, in
Cry-consensus were recognized by the T cell clones specific to each peptide. PBMC
from allergic patients induced higher proliferation under stimulation from Cry
consensus than individual peptides. Eighty-eight percent of the PBMC (15 of 17)
showed proliferation under the Cry-consensus stimulation. Thus, several major T
cell epitopes from Cry j 1 and Cry j 2 can be chosen in the design of peptide
based immunotherapeutics for the management of Japanese cedar pollinosis in
subjects having various types of HLA class II molecules.
PMID- 9647256
TI - Ubiquitination and dimerization of complement receptor type 2 on sheep B cells.
AB - Complement receptor type 2 (CR2) is a membrane-anchored glycoprotein that
specifically binds C3d, as well as other ligands, and plays diverse roles in
regulating immunity. Here we show that two distinct isoforms of CR2 are expressed
on the surface of sheep B lymphocytes. One (CR2no 150 kDa) is structurally
similar to known mammalian homologues while the other (CR2ub 190 kDa) has been
modified by the covalent attachment of ubiquitin to the cytoplasmic domain and is
identified for the first time. CR2no and CR2ub are expressed on the surface of
sheep B cells as noncovalently associated dimers and the external topography of
the two isoforms differs in some respect. The basis for these unusual higher
order structural properties may lie in the primary sequence of sheep CR2, since
the transmembrane domain contains a region resembling a rare 7-amino acid
dimerization motif, and two lysine residues in the cytoplasmic domain provide
potential sites for posttranslational ubiquitination. The primary structures of
sheep ubiquitin and C3d ligand are extensively conserved. In conjunction with the
results of separate in vivo studies, these findings suggest that selective
ubiquitination plays a role in modulating the higher-order structure and/or
expression of CR2 during B cell development.
PMID- 9647257
TI - SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production,
and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes.
AB - Nitric oxide (NO) is implicated in a number of inflammatory processes and is an
important mediator in animal models of rheumatoid arthritis and in in vitro
models of cartilage degradation. The pyridinyl imidazole SB 203580 inhibits p38
mitogen-activated protein (MAP) kinase in vitro, blocks proinflammatory cytokine
production in vitro and in vivo, and is effective in animal models of arthritis.
The purpose of this study was to determine whether SB 203580 could inhibit p38
MAP kinase activity, NO production, and inducible NO synthase (iNOS) in IL-1
stimulated bovine articular cartilage/chondrocyte cultures. The results indicated
that SB 203580 inhibited both IL-1 stimulated p38 MAP kinase activity in isolated
chondrocytes and NO production in bovine chondrocytes and cartilage explants with
an IC50 value of approximately 1 microM. To inhibit NO production, SB 203580 had
to be present in cartilage explant cultures during the first 8 h of IL-1
stimulation, and activity was lost when it was added 24 h following IL-1. SB
203580 did not inhibit iNOS activity, as measured by the conversion of arginine
to citrulline, when added directly to cultures where the enzyme had already been
induced, but had to be present during the induction period. Using a 372-bp probe
for bovine iNOS we demonstrated inhibition of IL-1-induced mRNA by SB 203580 at
both 4 and 24 h following IL-1 treatment. The iNOS mRNA levels were consistent
with NO levels in 24-h cell culture supernatants of the IL-1-stimulated bovine
chondrocytes used to obtain the RNA.
PMID- 9647258
TI - Systemic administration of endotoxin induces bronchopulmonary hyperreactivity
dissociated from TNF-alpha formation and neutrophil sequestration into the murine
lungs.
AB - Bronchopulmonary hyperreactivity (BHR), an increased responsiveness to
nonspecific bronchoconstrictor agents, is a well-known characteristic of
bronchial asthma. It has been recently suggested that the severity of this
disease is related to the endotoxin content of house dust. In the present report,
it is shown that the i.p. administration of bacterial LPS to mice is followed by
a marked early dose-dependent BHR in response to methacholine. The microscopic
examination showed no ultrastructural lesions of the lungs or of the airways, but
a marked neutrophil accumulation in the capillaries, as confirmed by an increase
of the lung content in the neutrophil enzyme marker myeloperoxidase. In parallel,
high levels of TNF-alpha were found in plasma as well as its transcripts in the
lung tissues. Using immunologic (anti-TNF-alpha and anti-granulocyte Abs), and
pharmacologic (dexamethasone and vinblastine) tools, it is demonstrated that BHR
is apparently neither related to the presence of neutrophils in the pulmonary
microvasculature nor to the synthesis of TNF-alpha.
PMID- 9647259
TI - Demonstration of human T lymphotropic virus type I (HTLV-I) tax-specific CD8+
lymphocytes directly in peripheral blood of HTLV-I-associated myelopathy/tropical
spastic paraparesis patients by intracellular cytokine detection.
AB - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
paraparesis (HAM/TSP) is an inflammatory neurologic disease caused by HTLV-I
infection and has been associated with elevated levels of several proinflammatory
cytokines in both serum and cerebrospinal fluid. It is unknown what kind of cells
secrete these cytokines and if HTLV-I Ags are associated with this phenomenon.
Here, we investigated the expression of cytokines in PBL from eight HAM/TSP
patients, nine HTLV-I-infected asymptomatic carriers, and seven healthy controls
by flow cytometry combined with intracellular cytokine staining. PBL were
cultured with brefeldin A without mitogen and IL-2 for 14 h. Under these
conditions, CD8+ cells produced proinflammatory cytokines including IFN-gamma,
TNF-alpha, and IL-2, which were significantly elevated in HAM/TSP patients. The
proportion of CD8+ cells producing IFN-gamma in HAM/TSP patients, asymptomatic
carriers, and healthy controls were, on average, 4.9, 0.4, and 0.3%,
respectively. IFN-gamma production by these CD8+ cells was suppressed by anti-HLA
class I Ab. Purified CD8+ cells from an HLA-A2 HAM/TSP patient produced IFN-gamma
by cocultivation with autologous CD4 cells, the main reservoir of HTLV-I in vivo,
or allogenic HLA-A2+ B cells pulsed with a known immunodominant HTLV-I tax
peptide. These data suggest that high levels of circulating HTLV-I-specific CD8+
T lymphocytes have the potential to produce proinflammatory cytokines and may
promote inflammatory responses to HTLV-I in HAM/TSP patients.
PMID- 9647260
TI - Lymphocyte activation gene-3 (LAG-3) expression and IFN-gamma production are
variably coregulated in different human T lymphocyte subpopulations.
AB - We evaluated the relationship between cytokine profile and the expression of the
lymphocyte activation gene-3 (LAG-3) in both T cell clones and polyclonal T cell
lines; LAG-3 is a CD4-like protein whose expression is reportedly restricted to
Th1/0 cells and dependent upon IFN-gamma. We found that, while LAG-3 was
expressed only by CD4+ T cell clones producing IFN-gamma, most CD8+ clones
producing IL-4 but not IFN-gamma (i.e., with a T cytotoxic-2-like profile) were
LAG-3+. The intensity of LAG-3 expression by CD8+ clones correlated with the
amount of released IFN-gamma, suggesting that this cytokine is not required for
expression but rather for the up-regulation of LAG-3. Flow cytometric analyses of
polyclonal T cell lines confirmed that LAG-3 could be expressed by both CD4+ and
CD8+ cells that did not contain cytoplasmic IFN-gamma. In these cell lines, large
proportions of CD4+ and CD8+ cells coexpressed LAG-3 and CD30, a putative marker
of Th2-like cells. Overall, our data do not support the earlier suggestion that
LAG-3 and CD30 are selective markers of T cells with type-1 and type-2 cytokine
profiles, respectively.
PMID- 9647261
TI - IFN-gamma receptor signaling is essential for the initiation, acceleration, and
destruction of autoimmune kidney disease in MRL-Fas(lpr) mice.
AB - CSF-1 and TNF-alpha in the kidney of MRL-Fas(lpr) mice are proximal events that
precede and promote autoimmune lupus nephritis, while apoptosis of renal
parenchymal cells is a feature of advanced human lupus nephritis. In the MRL
Fas(lpr) kidney, infiltrating T cells that secrete IFN-gamma are a hallmark of
disease. To examine the impact of IFN-gamma on renal injury in MRL-Fas(lpr) mice,
we constructed a IFN-gamma R-deficient strain. In MRL-Fas(lpr) mice lacking IFN
gamma R, circulating and intrarenal CSF-1 were absent, TNF-alpha was markedly
reduced, survival was extended, lymphadenopathy and splenomegaly were prevented,
and the kidneys remained protected from destruction. Mesangial cells (MC) that
were signaled through the IFN-gamma R induced CSF-1 and TNF-alpha in MRL-Fas(lpr)
mice. We detected a large number of apoptotic renal parenchymal cells in advanced
nephritis and determined that signaling via the IFN-gamma R induces apoptosis of
tubular epithelial cells (TEC), but not MC. By comparison, TNF-alpha induces
apoptosis in MC, but not TEC, of the MRL-Fas(lpr) strain. Thus, IFN-gamma is
directly and indirectly responsible for apoptosis of TEC and MC in MRL-Fas(lpr)
mice, respectively. In conclusion, IFN-gamma R signaling is essential for the
initiation (CSF-1), acceleration (CSF-1 and TNF-alpha), and apoptotic destruction
of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.
PMID- 9647262
TI - Experimental autoimmune encephalomyelitis induced with a combination of myelin
basic protein and myelin oligodendrocyte glycoprotein is ameliorated by
administration of a single myelin basic protein peptide.
AB - Multiple sclerosis is an autoimmune disease of the central nervous system in
which T cell reactivity to several myelin proteins, including myelin basic
protein (MBP), proteolipid protein, and myelin oligodendrocyte glycoprotein
(MOG), has been implicated in the perpetuation of the disease state. Experimental
autoimmune encephalomyelitis (EAE) is used commonly as a model in which potential
therapies for multiple sclerosis are evaluated. The ability of T cell epitope
containing peptides to down-regulate the disease course is well documented for
both MBP- and proteolipid protein-induced EAE, and recently has been shown for
MOG-induced EAE. In this study, we describe a novel EAE model, in which
development of severe disease symptoms in (PL/J x SJL)F1 mice is dependent on
reactivity to two different immunizing Ags, MBP and MOG. The disease is often
fatal, with a relapsing/progressive course in survivors, and is more severe than
would be predicted by immunization with either Ag alone. The MOG plus MBP disease
can be treated postinduction with a combination of the MOG 41-60 peptide
(identified as the major therapeutic MOG epitope for this strain) and the MBP Ac1
11[4Y] peptide. A significant treatment effect can also be obtained by
administration of the MBP peptide alone, but this effect is strictly dose
dependent. This MBP peptide does not treat the disease induced only with MOG.
These results suggest that peptide immunotherapy can provide an effective means
of mitigating disease in this model, even when the treatment is targeted to only
one component epitope or one component protein Ag of a diverse autoimmune
response.
PMID- 9647263
TI - In vitro effects of IL-12 on HIV-1-specific CTL lines from HIV-1-infected
children.
AB - We studied the in vitro effects of IL-12 on HIV-1-specific CTL lines derived from
PBMC of HIV-1-infected children. HIV-1-specific CTL lines were derived by
limiting dilution following Ag-specific stimulation of PBMC from HIV-1-infected
children and were maintained with repeated anti-CD3 stimulation. Following
incubation with IL-12 for 5 to 7 days, HIV-1-specific cytotoxicity was augmented
in a dose-dependent fashion (mean increase, 94 +/- 83 lytic units; p = 0.0006).
Experiments performed with CD3-blocking Abs and MHC-mismatched targets
demonstrated that the IL-12-enhanced activity was MHC restricted and dependent on
cells bearing CD3. The effect of IL-12 on proliferation of the CTL lines as
tested by [3H]TdR uptake was minimal, with stimulation indexes ranging from 1.25
to 4.9. The effects of IL-12 on cytotoxicity were not significantly altered by
addition of Ab to the IL-2R (anti-Tac) in quantities sufficient to block
exogenous IL-2 (p = 0.15), demonstrating that endogenous IL-2 activity is not
required for IL-12-enhanced cytolytic activity. Likewise, addition of
neutralizing Ab specific for IFN-gamma did not change IL-12-enhanced cytotoxicity
(p = 0.61). The in vivo role of IL-12 in the generation and the stimulation of
CTL remains to be determined; however, its ability to augment HIV-1-specific CTL
in vitro adds additional support for IL-12 as a candidate for immune-based
therapy of HIV-1.
PMID- 9647264
TI - C1 esterase inhibitor transfusions in patients with hereditary angioedema.
PMID- 9647265
TI - Immunodeficiency with elevated IgM, lymphoid hyperplasia, autoimmune anemia, and
thrombocytopenia.
PMID- 9647266
TI - Insect stings.
PMID- 9647267
TI - C1-esterase inhibitor transfusions in patients with hereditary angioedema.
AB - BACKGROUND: Hereditary angioedema results from the deficiency of C1-esterase
inhibitor (C1-INH), and C1-INH replacement would represent definitive treatment
for angioedema attacks. In Canada, C1-INH is available only on a compassionate
basis at select medical facilities. Our objective is to assess the efficacy of C1
INH transfusions during angioedema attacks at a single Canadian institution.
METHODS: A retrospective chart review of transfusion data between January 1, 1995
and June 30, 1996 was performed. Phone interviews with patients elicited their
opinions of the treatment. Data collected included the number and duration of
angioedema attacks, dose of transfused C1-INH, and side effects of treatment.
RESULTS: Of a cohort of 13 patients with hereditary angioedema, seven received
transfusions with C1-INH. Attacks totaled 87, and more than 100,000 units of the
product were transfused. The mean time for abatement of an attack after
initiation of transfusion was 50 +/- 8 minutes (1 SD). There were no reports of
adverse effects. Although patients were satisfied with the treatment, they raised
concerns regarding long-term safety and availability. CONCLUSIONS: C1-INH
transfusion is a satisfactory means of treating angioedema attacks.
PMID- 9647268
TI - Efficacy, safety, and effects on quality of life of salmeterol versus albuterol
in patients with mild to moderate persistent asthma.
AB - BACKGROUND: Salmeterol xinafoate is a long-acting, highly selective, beta2
adrenergic agonist that produces bronchodilation and clinically significant
improvement in pulmonary function for up to 12 hours in patients with asthma.
OBJECTIVE: To evaluate the impact on asthma-specific quality of life, efficacy,
and safety of salmeterol versus albuterol in adult patients with mild-to-moderate
persistent asthma. METHODS: A randomized, double-blind, double-dummy, parallel
group, multicenter study was conducted in 539 adult asthma patients over 12
weeks. Patients were randomized to receive either salmeterol 42 microg via
metered-dose inhaler twice daily or albuterol 180 microg four times daily. Upon
entry into the study, 46% of patients were being treated with an inhaled
corticosteroid and were allowed to continue treatment throughout the study.
Pulmonary function and asthma symptoms were monitored daily, and patients
completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after
4, 8, and 12 weeks of treatment. RESULTS: Treatment with salmeterol twice daily
produced significantly greater improvements from baseline in all quality of life
domain ("Activity Limitation," "Asthma Symptoms," "Emotional Function,"
"Environmental Exposure") scores and in the global AQLQ score at 12 weeks (P < or
= .038) compared with albuterol treatment four times daily. Pulmonary function
and asthma symptoms were also significantly improved with salmeterol compared
with albuterol. CONCLUSIONS: Salmeterol 42 microg administered twice daily is
significantly more effective than albuterol 180 microg four times daily for
improving asthma-specific quality of life, controlling asthma symptoms, and
improving pulmonary function in patients with mild-to-moderate persistent asthma.
Furthermore, those improvements were maintained over a 12-week period.
PMID- 9647269
TI - Northern blot identification of mRNA containing sequence for protein allergen,
Alt a1, in eight strains of Alternaria alternata.
AB - BACKGROUND: Concentrations of Alt a1, a major allergen from Alternaria alternata
extracts, exhibit significant batch-to-batch variability. This variability may
result from basic strain-related genetic differences or from environmental
influences such as growth conditions or extraction methods. OBJECTIVE: The
objective of this work is to determine if strain-to-strain allergen variability
in Alternaria alternata, Alt a1 allergen occurs at the nucleic acid level.
METHODS: We compared the content of mRNA for a segment known to contain sequence
coding for the reported N-termini of this allergen in eight strains of Alternaria
obtained from three individual sources grown under identical conditions. RNA was
extracted from rapidly growing mycelia and analyzed by northern blot analysis for
the content of a specific segment containing sequence for the Alt a1 allergen.
Blots were also analyzed for the content of a specific 5.8S rRNA segment.
RESULTS: The size of the mRNA for this protein was about 700 bases. Sequence for
the specific segment was found in all of the eight strains tested. When
normalized for extraction variabilities using the content of 5.8S rRNA, the
calculated concentrations of Alt a1 mRNA of seven of the eight strains were
similar. CONCLUSIONS: The results of these experiments suggest that this Alt a1
related allergen sequence is found in many strains of Alternaria and that
variabilities in allergen protein content noted previously result from
posttranslational events.
PMID- 9647270
TI - Clinical predictors of nasal secretory cell quantities in allergy clinic
patients.
AB - BACKGROUND: Nasal cytograms are useful in evaluating patients with inflammatory
disease of the nose and paranasal sinuses. When mucosal samples are taken with
curette and brush devices, significant numbers of non-leukocytic cells can also
be analyzed. OBJECTIVE: To examine two specific morphologic variations in granule
containing epithelial cells in nasal samples obtained from allergy clinic
patients and describe their clinical associations. These two cellular variants
consisted of goblet cells, with coalesced granules usually displacing the
nucleus, and discrete granular mucinous cells (DGMC), which show more discrete
granules not displacing the nucleus. METHODS: Patients from an adult allergy
clinic were studied prospectively for nasal mucosal cytology, historical clinical
data, nasal physical findings, serum IgE levels, and aeroallergen-specific IgE.
Proportions and absolute numbers of goblet cells and DGMC in the nasal mucosal
samples were related to other data using simple and multivariate analyses.
RESULTS: Both goblet cells and DGMC showed absolute number increases in patients
with observable nasal secretions. Discrete granular mucinous cell decreases were
also observed in patients with IgE levels greater than or equal to 200 IU/mL and
in asthmatic patients. In non-asthmatic patients with nasal eosinophilia, a
significantly greater proportion of DGMC was observed compared with other
patients (19.8 +/- 11.9% versus 8.5 +/- 5.9%, P = .007), while asthmatics with
nasal eosinophilia had mean DGMC quantities closer to that observed in patients
without nasal eosinophilia. Increases in goblet cell numbers were observed in
patients with specific IgE to aeroallergens compared with other patients (46.5 +/
46.7 versus 27.0 +/- 23.9, P = .014). Multivariate analysis confirmed that (1)
the presence of aeroallergen-specific IgE and (2) the presence of nasal
eosinophilia in the absence of asthma were differentially associated with
increases in goblet cells and DGMC, respectively. CONCLUSIONS: Increases in nasal
DGMC and goblet cells differentially relate to specific clinical patterns of
nasal cellular inflammation and aeroallergen hypersensitivity. The nasal
epithelial cell profile associated with nasal eosinophilia in asthmatics may
differ from that observed in non-asthmatic nasal eosinophilia.
PMID- 9647271
TI - Aquagenic urticaria: report of a case and review of the literature.
AB - OBJECTIVE: To present a case of aquagenic urticaria and to review the literature
regarding this very rare physical urticaria. METHOD: We described the clinical
history of a patient with aquagenic urticaria. A water challenge test was
performed, with plasma histamine levels measured before and after the challenge.
RESULT: Our patient presented with a history of severe itching and wheals within
five minutes of contact with water, regardless of its temperature or source (sea
or tap water). A water challenge produced hives but serum histamine levels did
not change. Prophylaxis with antihistamine or anticholinergic medications was not
effective. CONCLUSION: Exposure to water can cause urticaria in susceptible
patients and antihistamine and anticholinergic medication may not prevent the
reaction. The mechanism of this phenomenon remains poorly understood.
PMID- 9647272
TI - Eosinophils and pulmonary function: an epidemiologic study of adolescents and
young adults.
AB - BACKGROUND AND OBJECTIVE: In order to identify potential risk factors, other than
cigarette smoking, for lung function impairment, the relationships of peripheral
eosinophil count, bronchial responsiveness to inhaled histamine, skin test
reactivity and respiratory symptoms to pulmonary function results in a population
sample of 665 adolescents and young adults, aged 13 to 23 years. METHODS: Case
history, especially concerning smoking habits and respiratory symptoms, was
obtained by interview and a self administered questionnaire. Pulmonary function,
peripheral blood eosinophil counts, bronchial responsiveness to inhaled histamine
and skin test reactivity to common allergens were measured using standard
techniques. The relationships of peripheral blood eosinophil counts, symptoms of
asthma, cigarette smoking, bronchial responsiveness and skin test reactivity were
compared with FEV1, adjusted for age, sex, and height. RESULTS: The peripheral
eosinophil count was inversely correlated to FEV1 %predicted (P = .001); and
subjects with eosinophilia (defined as > .25 x 10(9) l(-1)) had significantly
reduced FEV1 %predicted compared with those without eosinophilia (95 +/- 13 %pred
and 102 +/- 16 %predicted, respectively, P = .001). A close direct correlation
was observed between blood eosinophils and histamine responsiveness (r = .60; P <
.001). In nonatopic subjects (n = 382), the FEV1 %predicted was significantly
lower in those with eosinophilia compared with those without. Subjects, who had
never smoked, who were nonatopic and nonasthmatic, and who had no evidence of
bronchial hyperresponsiveness, were found to have a weak but statistically
significant inverse relation between eosinophil count and FEV1 %predicted (r =
.14, P = .04). In the same subgroup, subjects with eosinophilia (n = 27) had
reduced FEV1 %predicted compared with those without (n = 177) (96 and 102,
respectively, P < .05). CONCLUSIONS: The findings of this study support the
theory that the role of the eosinophil leukocyte in obstructive pulmonary
diseases extends beyond its role in allergic reactions, suggesting that an
increased number of blood eosinophils reflects an inflammatory reaction in the
airways, which might lead to development of obstructive airflow limitation.
PMID- 9647273
TI - Comparison of three treatment regimens of inhaled sodium cromoglycate in the
management of adult patients with severe, steroid-dependent asthma.
AB - BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite
treatment with high doses of inhaled corticosteroids and co-administration of
oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To
investigate the relative efficacy of three treatment regimens of inhaled sodium
cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients
as determined by the reduction in the dose of oral corticosteroids and change in
lung function. METHODS: Open, randomized, group comparative trial of 12 weeks
duration in asthmatic patients attending a hospital outpatient department.
Patients whose asthma is (1) severe according to the classification of the
Japanese Society of Allergology, (2) stable, and (3) needing treatment with at
least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of
oral prednisolone per day. The three treatment regimens of inhaled sodium
cromoglycate were group A received sodium cromoglycate powder at a dose of 16
mg/day administered by a metered dose inhaler. Group N received sodium
cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer.
Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with
salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were
a change in the daily dose of oral corticosteroids and in lung function with
twice daily measurements of peak expiratory flow (PEF) recorded in the morning
(PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral
corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg
(95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage
reductions are all significant but with no differences between the groups. The
mean increase in PEF over the last 4 weeks of treatment compared with baseline
values was significant in all groups. The increases in group C are significantly
greater than those in the other groups. These changes are all significant and the
increases in group C are significantly greater than those in the other groups.
CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in
the management of adult patients with severe, oral steroid-dependent asthma. Of
the three methods of administration compared in this trial the most useful
immediate results were obtained when the drug was administered as an aqueous
solution mixed with salbutamol and delivered by a powered nebulizer.
PMID- 9647274
TI - Continuous nebulization therapy for asthma with aerosols of beta2 agonists.
AB - BACKGROUND: Various studies have demonstrated the benefits of continuous
nebulization therapy for delivering aerosols of the beta2 agonists such as
terbutaline sulfate or albuterol sulfate to patients with severe asthma and/or
impending respiratory failure. OBJECTIVE: The purpose of this investigation was
to explicate the operational factors associated with the use of nebulizers for
extended aerosol respiratory therapy including those factors that affect the
prescribed aerosol dosages and the relationship to actual delivery of prescribed
drugs to the respiratory airways of the lungs of a patient under treatment
conditions. METHODS: Operational characteristics and methods have been
investigated for use of long-running nebulizers for continuous nebulization
therapy. Factors considered were particle size distribution, setup conditions,
aerosolization concentrations and rates, delivery fraction of aerosol reaching
patient, and changes in medication concentration during extended operation. With
a large volume nebulizer, aerosols can be delivered to the patient without
dilution via a standard open mask for up to eight hours without refill. The
pneumatic HEART nebulizer with 240 mL reservoir was evaluated. RESULTS: The
nebulizer was operated from a single compressed air or oxygen source and found to
provide from 10 to 15 L/min of aerosol with 38 to 50 microL of aerosolized
medicine per liter of air (or oxygen) and utilize from 30 to 56 mL/hour of
medicinal liquid. The mass median aerodynamic diameter of the aerosol droplets
was found to be about 2.0 microm (sigma(g) = 2.7). Delivery efficiency to the
patient mask was about 90%. The aerosolized medicine delivered to the patient can
be increased by adjusting the flow rate of the gas source or changing the
solution concentration of medicine. Typically, several milligrams of drug can be
delivered to the patient as inhaled aerosol per hour of treatment of which about
one-quarter can be expected to be deposited in the lungs. During eight hours of
operation the concentration of medicinal solution increased by about a factor of
two because of water evaporation. CONCLUSIONS: Continuous nebulization therapy is
an important means of treating patients with severe asthma. Dosage criteria can
be established based on the operating characteristics of the nebulizer system,
drug solution concentration, and patient respiration.
PMID- 9647275
TI - Glucocorticoids inhibit proliferation and interleukin-4 and interleukin-5
secretion by aeroallergen-specific T-helper type 2 cell lines.
AB - BACKGROUND: Glucocorticoids play an important role in the treatment of allergic
disease. The atopic process, itself, may reduce the response of peripheral blood
mononuclear cells (PBMC) to these drugs. OBJECTIVE: In this study we compared the
effect of hydrocortisone (HC), beclomethasone (BDP), and mometasone (MF) on
interleukin (IL)-4 and IL-5 secretion by aeroallergen-specific T-helper type 2
cells (Th2) and proliferation of PBMC from atopic donors. METHODS: Cells were
incubated with drug before stimulating with phytohemagglutinin and assessing
proliferation (PBMC) and cytokine secretion (Th2). RESULTS: The glucocorticoids
concentration dependently inhibited proliferation and cytokine secretion, but had
less effect on proliferation of cells from severe atopics than on cells from
those whose symptoms required little treatment. The rank order of potency was MF
(average IC50 0.01 nM) > BDP (4.0 nM) > HC (250 nM). CONCLUSIONS: These
experiments demonstrate glucocorticoid inhibition of IL-4 and IL-5 secretion by
human Th2-like cells and proliferation of PBMC from severely and mildly allergic
donors.
PMID- 9647276
TI - Developmental changes of unbound theophylline.
PMID- 9647277
TI - Unenhanced and enhanced magnetic resonance imaging in the diagnosis of multiple
sclerosis.
AB - Initial enthusiasm about the role of magnetic resonance imaging (MRI) in the
diagnosis of multiple sclerosis decreased substantially with the notion that (a)
lesions of various pathological origins may resemble demyelinating plaques and
(b) a dissemination of lesions throughout the brain is not unique for multiple
sclerosis but may even be a "normal" finding. Current experience still does not
allow the identification of the aetiology of a single hyperintensity but has
identified multiple features of multiple sclerosis related signal abnormalities
which, in combination, provide rather high diagnostic accuracy. Useful
characteristics include the distribution of lesions such as a strictly
periventricular, infratentorial or juxtacortical location, and involvement of the
corpus callosum. The presence of contrast enhancement in some but not all lesions
that is, evidence of both old and new lesions-provides additional diagnostic
support. Improved instrumentation for imaging of the spine further extends the
diagnostic options. Intramedullary signal abnormalities are detected with
increased sensitivity and may disclose the presence of multiple lesions even in
patients with an equivocal or a negative MRI of the brain. The high sensitivity
to plaques and the opportunity to simultaneously rule out other gross
morphological damage justifies the use of MRI as the primary diagnostic modality
in the evaluation of multiple sclerosis.
PMID- 9647278
TI - Differential diagnosis of multiple sclerosis: contribution of magnetic resonance
techniques.
AB - It is widely accepted that magnetic resonance imaging (MRI) findings are not
totally specific for the diagnosis of multiple sclerosis. White matter lesions
that mimic those of multiple sclerosis may be detected in both normal volunteers
and patients harbouring different diseases. Virtually all the characteristic
features of multiple sclerosis are sometimes encountered in other conditions
affecting predominantly the white matter. Different conditions such as
vasculitis, subcortical atherosclerotic leukoencephalopathy, Lyme disease, or
acute disseminated encephalomyelitis can be virtually indistinguishable from
multiple sclerosis on conventional MR images. Also the FLAIR technique adds
little to the differential diagnosis. The calculation of magnetisation transfer
ratio (MT ratio) may be useful to better characterise some entities, such as
vasculitis, from multiple sclerosis.
PMID- 9647279
TI - The contribution of magnetic resonance imaging to the assessment of optic nerve
and spinal cord involvement in multiple sclerosis.
AB - Magnetic resonance imaging of the optic nerve and spinal cord in multiple
sclerosis has advanced considerably in the past decade. It is possible to
reliably detect intrinsic optic nerve and spinal cord lesions due to
demyelinating disease. Detection of these can assist diagnosis, especially in the
spinal cord. As demyelinating lesions in these structures are often symptomatic,
MR imaging in these regions also provides a special opportunity to obtain
insights into pathophysiological and pathogenetic mechanisms.
PMID- 9647280
TI - Clinical, neurophysiological, and magnetic resonance imaging correlations in
multiple sclerosis.
AB - Magnetic resonance imaging (MRI) has a pivotal role in diagnosis of multiple
sclerosis and is being increasingly used as a paraclinical measure to assess
treatment efficacy in clinical trials. However, the correlations between clinical
and MRI findings in patients with multiple sclerosis are weak and, therefore,
newer MR techniques are being developed to increase both MRI sensitivity for
detecting disease activity and its pathological specificity for better assessing
disease evolution. Evoked potentials (EPs) can be used to confirm the diagnosis
of multiple sclerosis and their abnormalities are correlated with symptoms and
signs referable to involvement of the corresponding nervous pathways. However,
their use is limited when assessing disease progression and monitoring clinical
trials in multiple sclerosis. Both magnetic resonance imaging (MRI) and evoked
potentials (EPs) provide information which cannot be obtained by clinical
evaluation, especially for assessing disease activity. Nevertheless, both these
paraclinical techniques cannot substitute for clinical measures of disability
when assessing disease progression and monitoring phase III clinical trials in
multiple sclerosis.
PMID- 9647281
TI - The lesion in multiple sclerosis: clinical, pathological, and magnetic resonance
imaging considerations.
AB - Despite the cause of multiple sclerosis remaining elusive, recent studies of the
disease using magnetic resonance imaging (MRI) and detailed pathological analysis
have provided new insights into the events involved in the evolution of the
lesion in multiple sclerosis. Most evidence points to disruption of the blood
brain barrier as the initial event in development of the lesion in multiple
sclerosis. It is thought that antigen specific T cells enter the nervous system,
recognise antigen, and begin a cytokine cascade that mediates disruption of the
blood-brain barrier seen on contrast enhanced MRI. Subsequently, the inflammatory
response is amplified and the effector stage leading to myelin damage is
initiated. The mechanism(s) causing myelin damage is uncertain. MRI and
pathological studies now indicate that damage to the axon may occur earlier in
lesion development than generally thought. Although T2 weighted MRI techniques
lack pathological specificity, considerable attention is now focused on studying
newer techniques that should provide greater insight into lesion development.
These include studies of hypointensities on T1 weighted images, proton
spectroscopy, magnetisation transfer imaging, and diffusion imaging. Hopefully,
these new techniques will provide a better understanding of events involved in
the multiple sclerosis lesion as well as an improved understanding of the
relation between disease as measured on MRI and that seen clinically.
PMID- 9647282
TI - Correlating immunological and magnetic resonance imaging markers of disease
activity in multiple sclerosis.
AB - Inflammation plays a central part in the pathogenesis of multiple sclerosis.
However, current surrogate magnetic resonance (MR) and immunological markers of
inflammation are weakly associated and correlate poorly with clinical
progression. Reasons for this are multiple and probably relate to the non
specific changes and insensitivity of current MR techniques, disease dynamics,
anatomical factors, and the temporal profile and poorly defined complexities of
the inflammatory reaction in multiple sclerosis. This paper provides an overview
of the principles involved in the monitoring of inflammation in multiple
sclerosis, discusses possible reasons for the weak correlation between MR and
immunological markers of inflammation, and briefly reviews the studies
correlating these modalities. In addition, the predictive values of MRI and CSF
oligoclonal immunoglobulin are compared in determining future progression to
clinically definite multiple sclerosis in patients presenting with clinically
isolated syndromes compatible with demyelination.
PMID- 9647283
TI - Standardisation and optimisation of magnetic resonance techniques for multicentre
studies.
AB - AIM: An approach to measuring physical quantities such as lesion load with MRI in
multicentre studies is presented. METHOD: Examples are given of imperfections in
current techniques: (1) a step change in a serial trial, giving an apparent (but
artefactual) decrease in total lesion volume in untreated patients with multiple
sclerosis; (2) inaccuracy (systematic error) in lesion volume, found by measuring
a phantom with lesions of known volumes; (3) spatial non-uniformity in the
radiofrequency coil sensitivity, giving gross image shading. When using the
magnetic resonance imaging (MRI) scanner as a scientific instrument to measure
physical quantities, accuracy (closeness to the truth, or lack of systematic
error), and precision (reproducibility, or lack of random error) are the keys to
success. Quality assurance procedures can utilise phantoms, normal control
subjects, and stable patients, and have to be included in serial studies and
trials. Between scanner agreement can perhaps be improved by attempting to
replicate an inaccurate procedure at each site; but it is more preferable to seek
accuracy and precision (as a perfectly accurate and precise procedure must give
the same results at all sites). CONCLUSION: Before being included in a serial
study, a measurement procedure should ideally demonstrate:(1) accuracy in a
phantom; (2) precision in repeated measurements on a phantom; (3) precision in
repeated measurements on human subjects.
PMID- 9647284
TI - Magnetic resonance imaging techniques to monitor short term evolution of multiple
sclerosis and to use in preliminary trials.
AB - Short term serial magnetic resonance imaging (MRI) studies have provided major
new insights into the natural history of multiple sclerosis, and are providing an
excellent tool for preliminary assessment of therapeutic effect. In early
relapsing-remitting and secondary progressive multiple sclerosis, monthly T2
weighted and gadolinium enhanced scanning discloses, on average, about 10 new or
enhancing lesions for each clinical relapse. This approach relies largely on the
detection of acute inflammatory MRI activity with blood-brain barrier break down-
as the importance of this for long term disability remains uncertain, these
methods for the present should not be used as the definitive assessment of
treatment outcome.
PMID- 9647285
TI - Magnetic resonance techniques to monitor the long term evolution of multiple
sclerosis pathology and to monitor definitive clinical trials.
AB - Magnetic resonance has provided a literal window on the brain to visualise the
actual pathology of MS as it evolves in the living patient. Natural history
studies disclosed that MRI visualised pathological activity was seen at 5 to 10x
the rate of clinical relapses. Utilising that knowledge, systematic MRI
monitoring has been used to supplement clinical monitoring to show the treatment
effect in several clinical trials. This chapter explains how MR techniques can be
used to further explore the evolution of in vivo pathology both in clinical
trials and natural history studies.
PMID- 9647286
TI - The role of non-conventional magnetic resonance techniques in monitoring
evolution of multiple sclerosis.
AB - Conventional magnetic resonance imaging (MRI) techniques have proved to be
extremely useful to monitor multiple sclerosis activity and evolution. The recent
development and clinical application of non-conventional MR techniques has the
potential to further increase the importance of MR in the evaluation of multiple
sclerosis by reducing the time needed for acquisition of the data, by improving
sensitivity, and by increasing the pathological specificity of the abnormalities
detected. In the present review, the main results obtained using these newer
techniques in the study of the natural history of the disease and the future
possible applications in clinical trials are presented.
PMID- 9647287
TI - The role of techniques characterised by faster acquisition times in the
evaluation of multiple sclerosis.
AB - Magnetic resonance imaging (MRI) methods with shorter acquisition times are
considered. Fast spin echo sequences allow faster scanning with images comparable
with conventional spin echo. Fast fluid attenuated inversion recovery (fast
FLAIR) may provide a more complete picture of multiple sclerosis evolution, but
more validation studies are still needed. Faster imaging methods, such as
turbogradient spin echo and echo planar imaging, have marked advantages for
uncooperative patients for diagnostic purposes and reduced motion related
artifacts but may involve sacrifices of signal to noise, contrast, spatial
resolution, and image quality. All methods are useful for clinical diagnosis,
with fast spin echo generally accepted as equivalent to conventional spin echo.
For quantitative evaluation in multiple sclerosis, further work is needed to
define the utility of the faster and ultrafast methods.
PMID- 9647288
TI - Magnetisation transfer imaging: theory and application to multiple sclerosis.
AB - Magnetic resonance imaging techniques based on magnetisation transfer exploit the
inherent heterogeneity of tissue with respect to relaxation times T1 and T2.
Contrast reflecting the interactions between distinct relaxation "environments"
may be exploited via novel quantitative analysis for potential gains in
specificity of the MR examination in multiple sclerosis.
PMID- 9647289
TI - Nuclear magnetic resonance relaxation in multiple sclerosis.
AB - OBJECTIVES: The theory of relaxation processes and their measurements are
described. An overview is presented of the literature on relaxation time
measurements in the normal and the developing brain, in experimental diseases in
animals, and in patients with multiple sclerosis. RESULTS AND CONCLUSION:
Relaxation time measurements provide insight into development of multiple
sclerosis plaques, especially the occurrence of oedema, demyelination, and
gliosis. There is also evidence that normal appearing white matter in patients
with multiple sclerosis is affected. What is now needed are fast and accurate
relaxation time measurement procedures, which cover the whole brain. Relaxation
time measurements could then provide an important tool for studying the
pathogenesis of demyelinating diseases and thus be useful in follow up studies.
PMID- 9647290
TI - Hypointense multiple sclerosis lesions on T1-weighted spin echo magnetic
resonance images: their contribution in understanding multiple sclerosis
evolution.
AB - The predictive value of T2-weighted imaging in multiple sclerosis is only
moderate, due to low specificity of high signal on such images. Among new MR
techniques with acclaimed higher pathological specificity, hypointense lesions on
moderately T1-weighted spin echo images show improved correlation with
disability. The degree of hypointensity of so called black holes correlates with
loss of magnetisation transfer, a marker of matrix destruction. Severe tissue
loss is also shown histopathologically in a post-mortem MR study of black holes.
In this review unresolved issues regarding black holes are discussed including
standardisation of sequences, definition of hypointensity, interobserver
variation in measuring lesion load with this technique, and significance of acute
black holes. The role of black holes in monitoring treatment efficacy is as yet
unexplored.
PMID- 9647291
TI - Diffusion magnetic resonance imaging in multiple sclerosis.
AB - This paper reviews the use of magnetic resonance diffusion imaging in studies of
multiple sclerosis. Firstly, the principles of diffusion imaging are explained
together with a discussion of the hardware and techniques required. The concept
of diffusion tensor imaging is introduced and images obtained using this method
are presented. Studies that have used diffusion imaging in patients with multiple
sclerosis and the implications of the results are discussed. There is an increase
in the diffusion coefficient of water molecules in the plaques of patients with
multiple sclerosis, compared with healthy brain. Some workers also report
increased diffusion in the normal appearing white matter of some patients with
multiple sclerosis. Possible mechanisms are given for these findings, together
with the experimental evidence to support them.
PMID- 9647292
TI - Functional magnetic resonance imaging in multiple sclerosis.
AB - Functional magnetic resonance imaging (fMRI) is a method that combines high
anatomical spatial resolution with the ability to localise function. Visual and
motor systems are among those that have received most attention. Yet the clinical
application is still limited. Recently, some investigators applied fMRI to study
patients with multiple sclerosis. Patients with partial motor weakness disclosed
a larger area of cortical activation bilaterally by contrast with healthy
volunteers when using the affected arm, whereas patients with optical neuritis
disclosed a smaller area of activation, when stimulating the affected eye. These
results show that different systems might react heterogeneously.
PMID- 9647293
TI - Quantitative assessment of magnetic resonance imaging lesion load in multiple
sclerosis.
AB - Changes of lesion load on yearly conventional spin echo (CSE) T2-weighted scans
of the brain from patients with multiple sclerosis, measured using computer
assisted techniques, are used to monitor long term disease evolution, either
natural or modified by treatment. Although lesion load measurements have several
advantages over clinical measures of outcome (they provide a more objective and
sensitive measure of disease evolution, which has a linear distribution and a
more strict relation with the underlying pathology), the poor correlation between
changes of lesion load and changes of disability is of concern when using such an
approach for monitoring multiple sclerosis trials. In this review, the main
sources of variation in T2 lesion load from brain MRI of patients with multiple
sclerosis will be considered, along with possible strategies to, at least
partially, overcome them. Also, some of the newer fully automated techniques to
segment multiple sclerosis lesions, which have been validated against manual
outlining, and a recently developed coregistration technique are presented. It is
hoped that a more reliable and standardised approach to lesion load measurements
in multiple sclerosis will lead to better correlation with clinical disease
course, to a higher confidence in the results of trials, and to reduced numbers
of scans needed to conduct the trials, thus improving cost efficiency and
reducing discomfort of the patients.
PMID- 9647294
TI - The use of magnetic resonance spectroscopy in the evaluation of the natural
history of multiple sclerosis.
AB - Magnetic resonance spectroscopic imaging (MRSI) can be used to define specific
chemical-pathological changes in the brain of patients with multiple sclerosis.
Magnetic resonance spectroscopy offers promise for improved definition of the
nature of individual lesions, the dynamics of their evolution, their effects on
normal appearing white matter, and their relation to clinical disability.
Combined multimodal MRSI studies of the brains of patients with multiple
sclerosis therefore soon may provide efficient, specific, and quantitative new
approaches to assessment of drug effects in therapeutic trials.
PMID- 9647295
TI - Measures of brain and spinal cord atrophy in multiple sclerosis.
AB - Although conventional magnetic resonance imaging (MRI) has greatly increased the
understanding of the pathophysiology of multiple sclerosis, its relation to the
development of disability is complex. More pathologically specific imaging
markers have therefore been sought to try and understand the underlying process
that is responsible for the progressive disability that so commonly occurs in
multiple sclerosis. Of these the most simple to understand conceptually is the
measurement of atrophy, which most probably represents axonal loss. Several
recent studies have shown that atrophy is a process closely linked with the
progressive phase of multiple sclerosis and worsening disability. Furthermore it
has also been shown that atrophy may evolve despite the absence of inflammatory
activity as judged by gadolinium enhanced MRI and thus its measurement gives
information in addition to that obtained from conventional MRI. Because of new
developments in imaging we are now able to measure atrophy reliably and
reproducibly. Hence the measurement of atrophy now provides objective markers by
which to evaluate putative treatment aimed at preventing disability in multiple
sclerosis.
PMID- 9647296
TI - Alzheimer's disease, amyotrophic lateral sclerosis, and transgenic mice.
PMID- 9647297
TI - Prevention of strokes and recurrent strokes.
PMID- 9647298
TI - The neurology of pregnancy.
PMID- 9647299
TI - "Summary measure" statistic for assessing the outcome of treatment trials in
relapsing-remitting multiple sclerosis.
AB - OBJECTIVES: To review the outcome measures commonly used in phase III treatment
trials of relapsing-remitting multiple sclerosis and to introduce a method of
data analysis which is clinically appropriate for the often reversible disability
in this type of multiple sclerosis. METHODS: The conventional end point measures
for disability change are inadequate and potentially misleading. Those using the
disability difference between study entry and completion do not take into account
serial data or disease fluctuations. Rigid definitions of "disease progression"
based on two measurements of change in disability several months apart, do not
assess worsening after the defined "end point", nor the significant proportion of
erroneous "treatment failures" which result from subsequent recovery from
relapses that outlast the end point. Assessing attacks merely by counting their
frequency ignores the variation in magnitude and duration. These problems can be
largely circumvented by integrating the area under a disability-time curve (AUC),
a technique which utilises all serial measurements at scheduled visits and during
relapses to summarise the total neurological dysfunction experienced by an
individual patient on any particular clinical scale during a study period.
CONCLUSIONS: The "summary measure" statistic AUC incorporates both transient and
progressive disability into an overall estimate of the dysfunction that was
experienced by a patient during a period of time. It is statistically more
powerful and clinically more meaningful than conventional methods of assessing
disability changes, particularly for trials which are too short to expect to
disclose major treatment effects on irreversible disability in patients with a
fluctuating disease.
PMID- 9647300
TI - High incidence and prevalence of multiple sclerosis in south east Scotland:
evidence of a genetic predisposition.
AB - OBJECTIVE: To determine the incidence and prevalence of multiple sclerosis in the
Lothian and Border Health Board Regions of south east Scotland. METHODS:
Incidence study: all patients were identified in whom a diagnosis of Poser
category probable or definite multiple sclerosis was made by a neurologist
between 1992 and 1995. Prevalence study: all patients known to have multiple
sclerosis who were alive and resident in the study area on 15 March 1995 were
recorded. RESULTS: The crude annual incidence rates of probable or definite
multiple sclerosis per 100000 population were the highest ever reported: 12.2
(95% confidence interval (95% CI) 10.8-13.7) in the Lothian Region and 10.1 (95%
CI 6.6-13.6) in the Border Region. A total of 1613 patients with multiple
sclerosis were resident in the study area, giving standardised prevalence rates
per 100000 population of 203 (95% CI 192-214) in the Lothian Region and 219 (95%
CI 191-251) in the Border Region. Prevalent cases were more likely than expected
to have a Scottish surname (risk ratio 1.24, 95% CI 1.14-1.34). CONCLUSION:
Orkney and Shetland were previously thought to have by far the highest prevalence
of multiple sclerosis in the world: about double that found in England and Wales.
However, the prevalence in south east Scotland is equally high, suggesting that
the Scottish population as a whole has a genetic susceptibility to the disease,
and undermining the hypothesis that patterns of infection specific to small
sparsely populated island communities are important in the causation of multiple
sclerosis.
PMID- 9647301
TI - Clinical relapses and disease activity on magnetic resonance imaging associated
with viral upper respiratory tract infections in multiple sclerosis.
AB - BACKGROUND: Although the risk of clinical attacks of multiple sclerosis seems to
be significantly increased with viral upper respiratory tract infections (URTI),
serological evidence for the reported association remains controversial. In
addition, although MRI is six to 10 times more sensitive than clinical
exacerbations in indexing disease activity, any possible association between URTI
and MRI activity has yet to be investigated. OBJECTIVES: To examine the relation
between URTI and disease activity, in multiple sclerosis patients participating
in a placebo controlled trial of interferon beta-1a, as indexed both by clinical
exacerbation rate and by the number and volume of gadolinium
diethylenetriaminepentaacetic acid (Gd-DTPA) enhancing lesions on MRI. "At risk"
periods were defined around symptomatic URTI, with or without serological
confirmation. RESULTS: The relative risk of clinical relapse for serologically
unconfirmed symptomatic URTI was 2.1 (p=0.004). Raised antiviral antibody titres
conferred a relative risk of multiple sclerosis exacerbations that was 3.4 times
higher than the "not at risk" periods (annual attack rates of 5.7 v 1.6,
respectively, p=0.006). There was no definite relation between the number or the
volume of active lesions on MRI and either symptomatic or serologically defined
at risk periods. CONCLUSIONS: These results confirm the previously reported
association between viral infections and multiple sclerosis exacerbations and
indicate that the relative risk may be even higher when viral infection is
serologically confirmed. However, the results, perhaps because of the confounding
effects of interferon beta-1a, do not provide convincing evidence of increased
blood-brain barrier breakdown or inflammation during periods of virally induced
immune stimulation.
PMID- 9647302
TI - Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E
polymorphism.
AB - OBJECTIVES: In mild Alzheimer's disease, SPECT imaging of regional cerebral blood
flow has highlighted deficits in the posterior association cortex, and later in
the disease process, the deficit spreads to involve the frontal cortex. The
sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The
effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The
hypothesis was that those patients with Alzheimer's disease who carry the sigma4
allele would have more severe cerebral hypoperfusion. METHODS: Thirty one
patients with Alzheimer's disease and eight age and sex matched control subjects
were examined in a three year longitudinal study. Patients with Alzheimer's
disease were divided into subgroups according to their number of sigma4 alleles.
Regional cerebral blood flow ratios referred to the cerebellum were examined by
99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of
polymerase chain reaction products with the restriction enzyme Hha1. RESULTS: All
patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion
compared with control subjects. The two sigma4 allele subgroups had the lowest
ratios at the baseline assessment in the parietal and occipital cortices, and at
the follow up in the temporal, parietal, and occipital cortices. They had the
highest reduction in percentage terms in the temporal and occipital cortices
compared with the other subgroups. However, the global clinical severity did not
differ at the baseline or follow up examinations between the subgroups.
CONCLUSION: Apolipoprotein E polymorphism is involved in the pathogenesis and
heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion
was found in the sigma4 allele subgroups. This might have implications for
therapeutic approaches in Alzheimer's disease.
PMID- 9647303
TI - Application of the MRC brain tumour prognostic index to patients with malignant
glioma not managed in randomised control trial.
AB - OBJECTIVES: The MRC brain tumour prognostic index, which uses clinical variables
to place patients in different outcome categories, has not been evaluated on a
cohort outside a randomised controlled trial. The aims of this study were to (a)
determine in a large cohort of patients, derived solely from one centre and not
in a clinical trial, whether the MRC prognostic index stratified patients for
outcome; (b) compare actual outcomes with those obtained in the original studies;
and (c) examine whether neuropathological diagnosis was an independent prognostic
variable. METHODS: The MRC prognostic index was calculated for 236 patients with
either glioblastoma or anaplastic astrocytoma managed at a dedicated neuro
oncology clinic in Edinburgh between 1989 and 1995. RESULTS: For this mixed
population of malignant glioma the median survival was 8.6 months. Two year
survival was 72.2% for patients with an MRC index score of 1-10; 36.3% for those
with an index score of 11-15; 25.1% for those scoring 16-20; 20.4% with those
scoring 21-25; 4.8% with those scoring 26-33; and 0% for those scoring 34-38.
Exclusion of 79 patients who would not have been eligible for the MRC studies
from which the index was derived, because they were either too old or did not
receive radiotherapy, still resulted in a similar pattern of stratification but
with significantly improved median survival times for the lowest two categories.
Multivariate analysis of prognostic variables in the Edinburgh cohort showed that
patients with anaplastic astrocytoma did significantly better than those with
glioblastoma (p<0.001). CONCLUSIONS: Although there were some differences in
median survival times between the patients in the original MRC studies and the
Edinburgh cohort in similar prognostic categories and a tendency to improved two
year survivorship in the Edinburgh cohort these differences have arisen because
(a) the Edinburgh cohort was accrued about 10 years later than the study has
shown that even outside the setting of a prospective controlled trial and with
relaxed inclusion criteria the Medical Research Council (MRC) prognostic index is
a robust predictor of outcome in patients with malignant glioma. Survival clearly
declines as the prognostic index increases. Moreover, the prognostic model can be
substantially improved by the addition of histology data, although there is some
evidence that this will require complex modelling procedures.
PMID- 9647304
TI - Long term results of botulinum toxin type A (Dysport) in the treatment of
hemifacial spasm: a report of 175 cases.
AB - OBJECTIVE: To describe the long term efficacy and side effects of the treatment
of hemifacial spasm with Dysport and to evaluate two different sites of injection
to hopefully reduce side effects. METHODS: This study was designed as a
prospective descriptive study. Injections were made subcutaneously around the
eye. Peak improvement was subjectively assessed by using a visual analogue scale
and reported in percentages (0-100%). Duration of improvement was assessed
subjectively and reported in months. RESULTS: Of 175 cases, 17 were lost to
follow up and were excluded. 855 treatments were injected in the remaining 158
patients with a median of 4 treatments. The response rate was 97%. Of 855
treatments, the adjusted mean peak and duration of improvement was 77.2 (95%
confidence interval (95%CI) 74.7-79.4)% and 3.4 (95%CI 3.2-3.6) months
respectively. In 158 patients (complete group), the long term results from the
first to the 12th treatment showed that the mean peak improvement ranged from
72.70 to 80.10% and the duration of improvement was 2.60 to 3.71 months. It
remained constant throughout (p=0.40, p=0.87 respectively). The most common side
effect was ptosis. Of the 158 patients, 21 completed 12 treatments (subgroup). A
separate analysis of this group disclosed a mean peak and duration of improvement
from the first to 12th treatments ranging from 70.00 to 78.10% and 2.65 to 4.31
months respectively. Analysis of variance with repeated measures showed no
significant variation of peak and duration of improvement over the first to the
12th treatments (p=0.38, p=0.38 respectively). Only 3% of the treatments were
unsuccessful but responded to subsequent treatments. The incidence of ptosis was
reduced from 27.17% to 9.68% by moving the injection site to the lateral part of
orbital orbicularis oculi without any loss of efficacy. The yearly cost of
Dysport is considerably less than Botox. CONCLUSION: This study is the first to
show, in detail, the long term results of treatments of hemifacial spasm with
Dysport. The efficacy is constant throughout orbicularis oculi. The efficacy of
Dysport is comparable with Botox in long term follow up.
PMID- 9647305
TI - Genetic polymorphisms adjacent to the CAG repeat influence clinical features at
onset in Huntington's disease.
AB - OBJECTIVES: To evaluate possible influences of CCG and delta2642 glutamic acid
polymorphisms adjacent to the (CAG)n trinucleotide repeat in Huntington's disease
gene IT15 on some clinical features (age and symptoms) at onset. METHODS: 84
patients and a control group of 68 unaffected relatives were studied. Patients
all belonged to a group of affected persons tested for molecular confirmation of
Huntington's disease. The length of the CAG repeat sequence in the IT15 gene and
the adjacent CCG and delta2642 polymorphisms were determined by quantitative
polymerase chain reaction. RESULTS: Two intragenic polymorphisms were studied:
(CCG)n and delta2642 glutamic acid. Patients were classified firstly according to
the size of the CCG rich segment adjacent to the CAG repeat into genotype groups
CCG 7/7, 7/8, 7/9, 7/10, and 10/10 and then according to delta2642 polymorphism
into genotype groups A/A (absence of the delta2642 deletion), A/B, and B/B
(presence of the delta2642 deletion in respectively one and two alleles). The
presence of delta2642 mutation was associated with a significant decrease in age
at onset, although there was no significant increase in CAG size. A good
correlation was found between the (CAG)n trinucleotide repeat size and the age at
onset in patients with genotype AA (r2=0.72). Within patients of the A/B genotype
group however, a significant correlation was found but with a drop of the r2
value to 0.44. No association was found between age at onset and the CCG
polymorphism. Although an increased percentage of patients within the A/A
genotype group had a neurological onset, we found no overall significant
association between CCG or delta2642 polymorphisms and the nature of symptoms at
onset. CONCLUSIONS: The delta2642 glutamic acid polymorphism did not affect CAG
repeat size nor the nature of symptoms at onset but seems to influence the age at
onset in patients with Huntington's disease.
PMID- 9647307
TI - Post-traumatic cerebral venous sinus air embolism.
PMID- 9647306
TI - Lightning stroke and neuropsychological impairment: cases and questions.
AB - OBJECTIVE: To objectify neuropsychological impairments in survivors of lightning
stroke with lasting complaints about poor concentration and inability to divide
their attention. DESIGN: A series of six cases of lightning stroke were studied.
All patients had lost consciousness and reported amnesia of varying length.
Assessment took place between one and four years after injury, ensuring that
their neurological state had stabilised. They were tested with a
neuropsychological battery with an emphasis on attention and memory. Personality
and emotional reaction to the accident were assessed with questionnaires and a
lightning fear scale. Complaints were recorded by means of a trauma complaints
list including 10 questions on symptoms of the post-traumatic stress disorder.
RESULTS: Patients reported fatigue and lack of energy as their main complaints.
In addition, poor concentration, irritability, and emotional lability were
mentioned often. Neuropsychological tests disclosed mild impairments in memory,
attention, and visual reaction times. Two patients could be classified as
depressed, and one of these also showed convincing signs of the post-traumatic
stress disorder. CONCLUSION: As the lasting complaints and impairments could not
be explained, for all six cases, as resulting from head injury concomitant with
lightning stroke, cerebral hypoxia or a post-traumatic stress syndrome, it is
concluded that lightning stroke can result in subtle cognitive impairments. It is
speculated that most complaints of these survivors are caused by a vegetative
dysregulation, a disorder that has often been noted in the literature on the
effects of electrical injury to the nervous system. Such a dysregulation might
cause both the main complaint of fatigue and the mild cognitive impairments
identified with the present test battery.
PMID- 9647308
TI - Mechanisms of second and further strokes.
AB - OBJECTIVES: The mechanisms underlying recurrent stroke may be complex and
multifactorial, but they have not been studied systematically. The aim was to
analyse the different patterns and pathophysiological mechanisms of second and
further strokes. METHODS: Recurrent stroke patterns and mechanisms were studied
in 102 patients admitted with second or further strokes to the stroke centre in
Lausanne University Hospital. RESULTS: The patients with an initial cardioembolic
stroke experienced recurrent stroke of the same type most often, followed by
those with initial non-lacunar non-cardioembolic stroke, brain haemorrhage, and
lacunar stroke (77%, 65%, 58%, and 48% respectively). Forty two per cent of the
recurrent strokes in patients with an initial brain haemorrhage were ischaemic,
whereas patients with ischaemic stroke only occasionally suffered brain
haemorrhage (5%). In patients with brain haemorrhage, the lobar location
predominated in both the first and all episodes (69% and 78% respectively),
suggesting a small, occult arteriovenous malformation or cerebral amyloid
angiopathy rather than hypertensive small artery disease. The functional
disability of patients after an initial lacunar stroke was significantly better
than in patients with other stroke subtypes (p<0.001), but the difference became
non-significant after recurrent stroke (p=0.26). CONCLUSIONS: Most of the
recurrent strokes were of the same type as the first episode for both
cardioembolic and non-lacunar non-cardioembolic stroke, however, about half of
the patients with an initial brain haemorrhage or a lacunar stroke experienced
other types of stroke recurrently. The findings suggest that the coexistence of
multiple aetiologies may play a major part in determining the mechanism of stroke
recurrence. The study is an important step in understanding the patterns of
stroke recurrence, which may be critical for better prevention.
PMID- 9647309
TI - Auditory evoked neuromagnetic response in cerebrovascular diseases: a preliminary
study.
AB - OBJECTIVES: Magnetoencephalography (MEG) measures aspects of the function of the
auditory cortex of the human brain with high spatial resolution. The objective
was to determine whether MEG also accurately identifies the auditory cortex of
the brain in patients with ischaemic stroke. METHODS: The auditory evoked
magnetic field (AEF) was examined after stimuli of 1 kHz tone bursts in 24 stroke
patients without apparent infarcts in the auditory cortex, and compared the
topography of sources of 50 ms (P50m) and 100 ms latency deflections (N100m), the
most prominent components of middle and long latency AEFs, with that of 12 normal
subjects. Cerebral haemodynamics in and around the auditory cortex were evaluated
using PET. RESULTS: In nine of 24 stroke patients, the accurate magnetic sources
of P50m or N100m were not identified. The distribution of P50m sources varied
more widely than N100m. Eight of these nine patients had severe stenotic lesions
in the carotid or middle cerebral arterial trunks. Patients with abnormal P50m
responses had decreased supratemporal and hemispheric blood flow compared with
patients with normal P50m responses. CONCLUSIONS: These findings suggest that
large vessel disease with disturbed cerebral haemodynamics in and near the
auditory cortex tend to affect AEFs, especially the middle latency components.
This is the first combined study of MEG and PET to show a significant correlation
between AEF responses in stroke patients and their PET indices.
PMID- 9647310
TI - Diabetic neuropathic cachexia: report of a recurrent case.
AB - Diabetic neuropathic cachexia is an uncommon peripheral neuropathy associated
with diabetes mellitus and characterised by profound weight loss and painful
dysaesthesias over the limbs and trunk. The pathophysiological basis of this
disorder remains unknown and there have been no published cases of recurrent
episodes. A hispanic man who experienced two episodes of diabetic neuropathic
cachexia over a seven year period is described.
PMID- 9647311
TI - Hermann von Helmholtz (1821-94)
PMID- 9647312
TI - An unusual course of progressive multifocal leukoencephalopathy in a patient with
idiopathic CD4+ T lymphocytopenia.
AB - A case is reported of idiopathic CD4+T lymphocytopenia with progressive
multifocal leukoencephalopathy and cervical lymph node tuberculosis. A 57 year
old Japanese man presented with cervical lymphadenopathy and progressive
neurological deficits, and six months later he developed akinetic mutism. He had
a persistent severely depressed number of circulating CD4+T lymphocytes in the
absence of human immunodeficiency virus infection. T1 weighted MRI showed a
diffuse decreased signal intensity limited to the white matter without mass
effect. A brain biopsy specimen had a morphology similar to that of progressive
multifocal leukoencephalopathy. Polyomavirus antigen was detected in the brain
lesion, and viral DNA was identified in nucleated blood cells and urine.
Unusually this serious medical condition has lasted for more than three years
without remission. To our knowledge this is the first patient with CD4+T
lymphocytopenia with progressive multifocal leukoencephalopathy, suggesting that
similar opportunistic infections should be considered even in previously normal
people.
PMID- 9647313
TI - Intracerebral temperature in patients with hydrocephalus of varying aetiology.
AB - Brain temperature was measured at various depths beneath the pial surface in
patients with hydrocephalus of varying aetiology. Temperature increased gradually
with depth in all patients, with the highest temperature found in the ventricle.
The difference between intraventricular and rectal temperatures (delta v-r) was
greater in patients who underwent continuous ventricular drainage than in
patients who underwent ventriculoperitoneal shunt (continuous ventricular
drainage; 1.2 (SD 0.40) degrees C, mean (SD), n=5 v ventriculoperitoneal shunt;
0.4 (SD 0.45) degrees C, n=16; p< 0.05). The difference between intracerebral and
rectal temperatures (delta b2-r) was also greater in patients with continuous
ventricular drainage than in patients with ventriculoperitoneal shunt (continuous
ventricular drainage; 0.1 (SD 0.86) degrees C, n=5 v ventriculoperitoneal shunt;
0.7 (0.86) degrees C, n=16; p< 0.05). Among patients with normal pressure
hydrocephalus, these differences were greater in the patients with better
outcomes after shunt surgery than in the less improved group (delta v-r; 0.7 (SD
0.27) degrees C, n=7 v 0.1 (SD 0.40) degrees C, n=5, p< 0.01, delta b2-r; -0.2
(SD 0.61) degrees C, n=7 v -1.4 (0.90) degrees C, n=5, p< 0.01).
PMID- 9647314
TI - The selective inability to draw horizontal lines: a peculiar constructional
disorder.
AB - A patient is described who was affected by degenerative dementia and who
developed severe constructional apraxia. She showed a dissociation between the
construction of horizontal lines (impaired) and oblique or vertical lines
(spared) which has never been reported previously. A battery of tests disclosed
that this phenomenon was consistent across a range of experimental conditions and
that a similar dissociation was evident in perceptual and representational
domains. This peculiar clinical finding suggests that mental representations of
horizontal and vertical spatial relations in an egocentric coordinate system are
functionally dissociated.
PMID- 9647315
TI - Persistent loss of tyrosine hydroxylase immunoreactivity in the substantia nigra
after neuroleptic withdrawal.
AB - A 37 year woman developed neuroleptic induced parkinsonism that persisted long
after the drug had been discontinued. This prompted a study of the effect of an
eight week course of haloperidol (HAL) followed by two week withdrawal, on
dopaminergic neurons of the substantia nigra in rats. Animals treated with HAL
showed a highly significant 32%-46% loss of tyrosine hydroxylase (TH)
immunoreactive neurons in the substantia nigra, and 20% contraction of the TH
stained dendritic arbour. Neuroleptic drug induced downregulation of nigral
dopaminergic neurons may help to explain the persistent parkinsonism found in
many patients after withdrawal of medication.
PMID- 9647316
TI - Intracranial haemodynamics during attenuated responses to electroconvulsive
therapy in the presence of an intracerebral aneurysm.
AB - OBJECTIVES: This report describes successful anaesthesia and electroconvulsive
therapy (ECT) in a patient with an unruptured basilar artery aneurysm. ECT is
associated with a hyperdynamic state characterised by arterial hypertension,
tachycardia, and considerably increased cerebral blood flow rate and velocity.
These responses pose an increased risk for subarachnoid haemorrhage when an
intracranial aneurysm coexists. METHODS: A 54 year old woman presented for ECT.
She had a 20 year history of major depression which was unresponsive to three
different antidepressant drugs. There was also an unruptured 5 mm saccular
aneurysm at the basilar tip, which had been documented by cerebral angiography,
but its size had remained unchanged for the previous four years. After she
declined surgical intervention, she gave informed consent for ECT. During a
series of seven ECT sessions middle cerebral artery flow velocity was recorded by
a pulsed transcranial Doppler ultrasonography system. She was pretreated with 50
mg oral atenolol daily, continuing up to the day of the last ECT and immediately
before each treatment, sodium nitroprusside was infused at a rate of 30
microg/min, to reduce systolic arterial pressure to 90-95 mm Hg. RESULTS:
Systolic flow velocity during the awake state ranged from 62-75 cm/s, remaining
initially unchanged with sodium nitroprusside infusion. After induction of
anaesthesia (0.5 mg/kg methohexitone and 0.9 mg/kg succinylcholine), flow
velocities decreased to 39-54 cm/s, reaching maximal values of 90 cm/s (only 20%
above baseline) after ECT. These flow velocities recorded post-ECT were
considerably below the more than twofold increase recorded when no attenuating
drugs were used. Systolic arterial blood pressure reached maximal values of 110
140 mm Hg and heart rate did not exceed 66 bpm. Rapid awakening followed each
treatment, no focal or global neurological signs were apparent, and the patient
was discharged in remission. CONCLUSION: In a patient with major depression and a
coexisting intracerebral saccular aneurysm who was treated with ECT, the
combination of beta blockade with atenolol and intravenous infusion of sodium
nitroprusside prevented tachycardia and hypertension, and greatly attenuated the
expected increase in flow velocity in the middle cerebral artery.
PMID- 9647317
TI - Schroeder van der Kolk: the soul and epilepsy.
PMID- 9647318
TI - Dopa responsive dystonia with Turner's syndrome: clinical, genetic, and
neuropsychological studies in a family with a new mutation in the GTP
cyclohydrolase I gene.
AB - A 26 year old woman with dopa responsive dystonia and cytogenetically confirmed
Turner's syndrome had bilateral globus pallidus hypointensity on brain MRI. Among
the living members of a five generation pedigree the patient's mother and the
mother's sister also had dopa responsive dystonia; a maternal grandfather had
senile parkinsonism, his niece isolated postural tremor. No other family member
had Turner's syndrome. A new missense mutation in exon I of the gene of GTP
cyclohydrolase I was found in the three family members with dopa responsive
dystonia. With levodopa substitution the patients with dopa responsive dystonia
improved clinically as well as in quantitative tests on hand tapping, verbal and
performance IQ, concept formation, and set shifting abilities.
PMID- 9647319
TI - Ultrastructural characterisation of the M protein in nerve biopsy of patients
with POEMS syndrome.
AB - To learn more about the mechanisms of nerve lesions in POEMS syndrome, nerve
specimens from four patients were studied with an immunogold method at the
ultrastructural level to detect and localise the M protein in the different nerve
compartments. An indirect immunolabelling technique was applied on 4% PFA fixed
and LR White embedded nerve specimens. Antisera against IgG, IgA, IgM, and lambda
and kappa light chains were used as primary antisera. Morphological studies
disclosed an important axonal loss in association with the demyelinative process.
Endoneurial deposits of immunoglobulins were found in all cases. In the patient
with the most severe form of neuropathy, diffuse deposits were present in the
endoneurial space, especially in the subperineurial area. In the other patients,
occasional deposits of the M protein were found in the myelin sheath (n=2); or
between cells (n=1). No deposit was found in the axons. The class of the M
protein labelled in the nerve corresponded to that detected in the serum in three
of four patients, with labelling of two heavy chains in one patient.
Immunolabelling of the M protein on the myelin sheath, Schwann cells, and in the
endoneurial space favour a direct role of the M component in the lesions of nerve
fibres, and justify active treatment of the plasmacytic proliferation.
PMID- 9647320
TI - An unusual enhancement of motor performance during bimanual movement in
Parkinson's disease.
AB - In both clinical and laboratory tests, patients with Parkinson's disease have
considerable difficulty in performing different manual tasks simultaneously with
the two hands. The present study reports on an unusual enhancement in performance
under such conditions in a substantial proportion of patients tested. When
performed at the same time as repetitive tapping tasks, the ability to rapidly
place pegs in holes improved in almost half of the patients compared with
unimanual performance of the peg task. Various possible explanations are
considered for this unusual finding. The two most plausible, and testable, relate
to either the withdrawal of attention from the task permitting a more automatic
mode of execution, or a facilitation provided by sensory feedback from the
simultaneous tapping task.
PMID- 9647321
TI - Age of onset in patients with Alzheimer's disease with different apoE genotypes.
PMID- 9647322
TI - Sudden bilateral deafness: lateral inferior pontine infarction.
PMID- 9647323
TI - Surgical treatment of quadrigeminal plate lipoma presenting with seizures and
behavioural disorders.
PMID- 9647324
TI - Lambert-Eaton myasthenic syndrome and non-pulmonary small cell carcinoma.
PMID- 9647325
TI - Untreated hepatitis C may provoke myasthenia gravis.
PMID- 9647326
TI - Does nitric oxide regulate smooth muscle cell proliferation? A critical
appraisal.
AB - Smooth muscle proliferation is involved in the pathogenesis of atherosclerosis,
restenosis after angioplasty and vein graft failure due to neointimal
hyperplasia. Nitric oxide (NO) inhibits smooth muscle cell growth in vitro and
experimental neointimal hyperplasia in vivo, suggesting a role for NO as a
regulator of smooth muscle cell proliferation. NO is also involved in the control
of numerous other vascular functions including platelet and inflammatory cell
adhesion, vascular reactivity and endothelial permeability. This review
critically examines the experimental and clinical evidence that supports a role
for NO as a modulator of smooth muscle cell proliferation, with an emphasis on
the multiple mechanisms by which NO acts on vascular lesions.
PMID- 9647327
TI - Regulation of insulin-like growth factor-1 expression in vascular endothelial
cells by the inflammatory cytokine interleukin-1.
AB - Insulin-like growth factor-1 (IGF-1) has important roles in vascular physiology
and pathologies such as atherosclerosis. However, the factors that control
expression of this growth factor in human vascular cells are largely unknown. In
this study the effects of the inflammatory cytokine interleukin-1 (IL-1) on IGF-1
mRNA and peptide synthesis was examined in human endothelial cells. Cultured
human umbilical vein endothelial (HUVE) cells were challenged with interleukin-1
and IGF-1 Ea and Eb mRNA levels were determined by nuclease protection assays and
reverse transcription/polymerase chain reaction. IL-1 caused a dramatic increase
in IGF-1 Ea mRNA in HUVE cells. Transcript levels peaked between 2 and 4 h of IL
1 treatment and declined over the subsequent 4 h. Consistent with its effect on
mRNA, the inflammatory cytokine causes a 3-fold stimulation in production of IGF
1 peptide from endothelial cells. These results demonstrate increased IGF-1 mRNA
and peptide in vascular endothelial cells stimulated with IL-1. This suggests
that under conditions of local inflammation at the vessel wall the direct action
of IL-1 on endothelium can lead to induction of IGF-1 which could promote the
intimal hyperplasia often seen in these circumstances.
PMID- 9647328
TI - Expression of mRNA for phospholipase A2, cyclooxygenases, and lipoxygenases in
cultured human umbilical vascular endothelial and smooth muscle cells and in
biopsies from umbilical arteries and veins.
AB - Arachidonic acid (AA) is released by phospholipase A2 (PLA2) and then converted
into vasoactive and inflammatory eicosanoids by cyclooxygenases (COX) and
lipoxygenases (LOX). These eicosanoids are important paracrine regulators of
vascular permeability, blood flow, local pro- and anticoagulant activity and they
play a major role in the local inflammatory response. We have investigated the
presence of mRNAs for PLA2 and for isoforms of COX and LOX in both human
endothelial cells (EC) and in human smooth muscle cells (SMC) in culture and in
vascular biopsies of human umbilical veins (HUVB) and arteries (HUAB) by using
the reversed transcription-polymerase chain reaction (RT-PCR) technique. Results
show detectable levels of PLA2 type IV (cPLA2) in cultured EC and SMC and in
vascular wall biopsies from HUAB and HUVB. The cultured EC and SMC demonstrate
higher levels of both COX-1 and COX-2 with PCR analyses than do vascular wall
biopsies from HUAB and HUVB. This indicates a difference in the native expression
of COX-1 and COX-2 in cultures of EC and SMC compared to that in biopsies from
intact vessel walls. The EC and SMC in culture do not express mRNA for 5-LOX,
that was, however, expressed in the vascular wall biopsies. This speaks in favour
of a constitutive, i.e. in vivo expression of 5-LOX in SMC in the vascular wall
of both umbilical vein and arteries. Thus results from in vitro studies of
constitutive COX and LOX expression in EC and vascular SMC in culture cannot
simply be extrapolated to represent in vivo conditions.
PMID- 9647329
TI - A platelet-activating factor antagonist (WEB 2170) preserves endothelium
dependent vasodilatation and prevents development of a neo-intima induced by a
periarterial collar in rabbit carotid arteries.
AB - Platelet-activating factor (PAF) may be involved in adhesion of leucocytes and
migration of cells during vascular remodelling for it is expressed in leucocytes
after cytokine priming and is required for cell adhesion. We studied the effects
of WEB 2170, a potent PAF antagonist, on the development of an atheroma-like neo
intima induced by a peri-arterial collar in rabbits. Either WEB 2170 (3
mg/kg/day) or vehicle was given by subcutaneous injection once a day for 4 or 9
days, and on day 3 peri-arterial collars were applied to both carotid arteries in
all animals. Two or 7 days after implanting the collars vasodilator responses to
the endothelium-dependent vasodilator, acetylcholine and the endothelium
independent vasodilator, sodium nitroprusside were studied in isolated artery
rings from both groups of rabbits. Neo-intima formation after 7 days (day 10 of
treatment) was measured by light microscopy as the ratio of cross-sectional areas
of intima and media, and expression of inducible nitric oxide synthase (iNOS) was
studied by immunohistochemistry. PAF-induced platelet aggregation ex vivo was
inhibited specifically in WEB 2170-treated rabbits. At day 5, acetylcholine
induced vasorelaxation in collared artery rings was markedly impaired as compared
to control sections from both vehicle- and WEB 2170-treated rabbits. At day 10,
acetylcholine-induced vasorelaxation in collared artery rings from vehicle
rabbits was markedly less than in controls, but in WEB 2170-treated rabbits, the
acetylcholine response in collared arteries was similar to control sections.
Intimal thickening was much reduced in WEB 2170-treated rabbits, ratios of
intima/media areas being vehicle: 0.21 +/- 0.02 (n = 5) and WEB 2170: 0.07 +/-
0.01 (n = 7; p < 0.01). Immunofluorescence showed expression of iNOS only in the
neo-intima of vehicle-treated, collared arteries, but not in the residual neo
intima of WEB 2170-treated, collared arteries. These results suggest that WEB
2170 is effective in preserving endothelial function, prevents the development of
neo-intima and blocks iNOS expression in the neo-intima in this model.
PMID- 9647330
TI - Inhibition of vascular smooth muscle cell migration by intact endothelium is
nitric oxide-mediated: interference by oxidised low density lipoproteins.
AB - Migration of vascular smooth muscle cells (SMCs) leading to neointimal
hyperplasia is an early and cardinal feature of atherogenesis. Migration of rat
aortic SMCs from an upper chamber towards a lower one has been studied in a
microchemotaxis (Boyden) chamber. Spontaneous migration of SMCs was practically
prevented by the presence of endothelium in the lower chamber and was reduced if
endothelial cells were substituted with endothelial cell-conditioned medium.
Endothelial cells which had been treated with either the inhibitor of protein
synthesis cycloheximide or nitric oxide synthesis N(G)-nitro-L-arginine showed no
inhibitory effect on SMC migration. Addition of a nitric oxide donor S-nitroso-N
acetylpenicillamine to cell-free medium in the lower chamber prevented SMC
migration. Addition of native LDL to endothelial cells had no effect on SMC
migration, while (UV light) oxidised LDL completely abolished the inhibitory
effect of endothelial cells on SMC migration. It is concluded that via nitric
oxide, endothelium exerts a powerful inhibitory effect on SMC migration. This
effect of intact endothelium is completely abolished by oxidised LDL applied in a
concentration, which is relevant to those measured in plasma of patients with
severe coronary artery disease. It is suggested that oxidised LDL may contribute
to the pathogenesis of atherogenesis by stimulating migration of SMCs from media
to the intima via abolishing the physiological inhibitory effect of normal
endothelium.
PMID- 9647331
TI - Reactivity of small intramyocardial arteries from atherosclerotic and non
atherosclerotic human hearts.
AB - Little is known about how the vascular reactivity of the coronary
microcirculation is affected by upstream atherosclerotic disease. We have
examined, with a wire myograph, the responses of intramyocardial arteries from
hearts in which the epicardial vessels were either free of atherosclerotic
lesions (non-diseased group) or were affected by atherosclerosis (diseased
group). Vasodilator responses of preconstricted vessels to substance P (84.1 +/-
12.6 compared to 42.0 +/- 19.7%) were less in vessels from the diseased group (p
< 0.05). In contrast, the relaxation to bradykinin (70.2 +/- 21.2 compared to
100.6 +/- 7.9%) was increased in vessels from the diseased group (p < 0.05). The
dilator responses to acetylcholine, adenosine diphosphate, histamine and sodium
nitroprusside showed no significant differences between arteries from each group.
5-Hydroxytryptamine was without any significant vasodilator effect in arteries
from either group. Assessment of contractile function revealed that the responses
to 5-hydroxytryptamine, acetylcholine, U46619, endothelin-1 and L-N(G)
monomethylarginine in each group were not significantly different. Histamine,
noradrenaline and dopamine were without any significant contractile response.
These results demonstrate that upstream atherosclerosis does not confer any
global impairment of endothelium-dependent vasorelaxant responses or smooth
muscle hyperreactivity to vasoconstrictors in the arteries that penetrate the
myocardium.
PMID- 9647332
TI - Coexpression of mRNAs for P2X1, P2X2 and P2X4 receptors in rat vascular smooth
muscle: an in situ hybridization and RT-PCR study.
AB - The expression of mRNAs for three P2X receptor subtypes (PX21, P2X2, P2X4) in the
rat vascular system was studied by in situ hybridization and RT-PCR. In heart
sections mRNAs transcripts for all three receptors were colocalized in smooth
muscle cells of coronary vessels, while no specific positivity was apparent in
myocardium. Coexpression of P2X receptor mRNA transcripts were also observed in
other peripheral vessels, including aorta, pulmonary artery, internal and
external iliac arteries, renal artery and femoral artery. By contrast, no mRNA
transcripts of the above receptors were found in the superior mesenteric artery.
RT-PCR performed on microdissected tissues (coronary arteries, aorta and
myocardium from various heart areas) confirmed the presence of P2X1, P2X2 and
P2X4 receptor mRNAs. Furthermore, in the same tissues two splice variants of the
P2X2 receptor were identified. These results reveal an important molecular
heterogeneity of P2X receptors, thus substantiating the possibility of a
heteropolymeric assembly of ATP-gated ion channels in the cardiovascular system.
PMID- 9647333
TI - Gene expression of endothelin-1 and ET(A) and ET(B) receptors in human cirrhosis:
relationship with hepatic hemodynamics.
AB - Previous experimental studies have suggested that the paracrine endothelin system
may participate in the regulation of hepatic hemodynamics in cirrhosis. The
present study assesses the relationship between increased portal pressure and
preproET-1, ET(A) receptor and ET(B) receptor gene expression in human cirrhosis.
PreproET-1, ET(A) receptor and ET(B) receptor mRNA abundance was estimated by
quantitative PCR in human hepatic tissue from subjects with normal liver and in
cirrhotic patients in whom a hepatic hemodynamic study was performed. The
expression of the three transcripts was significantly higher in liver samples of
cirrhotic patients than in those obtained from subjects without any histological
alteration. Moreover, while no significant correlation was found between preproET
1 mRNA abundance and portal pressure, there was a highly significant direct
relationship between ET(A) and ET(B) receptor gene expression and portal pressure
in cirrhotic patients. These results indicate that the liver paracrine endothelin
system is overactivated in human cirrhosis and that a direct relationship exists
between endothelin receptor mRNA abundance and the degree of portal hypertension
in these patients.
PMID- 9647334
TI - Effect of troglitazone on fibrinolysis and activated coagulation in patients with
non-insulin-dependent diabetes mellitus.
AB - The objective of this study was to determine if treatment of non-insulin
dependent diabetes mellitus (NIDDM) patients with the "insulin sensitizer"
troglitazone, both as monotherapy and in combination with insulin, corrects the
impaired fibrinolysis and activated coagulation associated with NIDDM. Patients
participating in two clinical trials comparing troglitazone and placebo in
patients with NIDDM were studied at the time of randomization and after 26 weeks
of treatment. Eighteen patients were treated with troglitazone (ten in
combination with insulin and eight as monotherapy) and eight were treated with
placebo (four in each trial). Plasma concentrations of plasminogen activator
inhibitor (PAI-1), prothrombin fragment F1+2, fibrinogen, and von Willebrand
Factor (vWF) activity were measured. Plasma PAI-1 concentrations fell
significantly from a mean of 68.8 +/- 32.3 ng/mL to 40.4 +/- 20.4 in the
troglitazone treated group, but did not change significantly in the placebo
treated group. Plasma PAI-1 concentrations were elevated in 15 patients treated
with troglitazone and fell to normal in eight of them. There was no significant
change in plasma F1+2, vWF, and fibrinogen, but plasma C-peptide and triglyceride
concentrations fell significantly with troglitazone. This study demonstrates that
troglitazone treatment is associated with a significant fall in plasma PAI-1
antigen concentrations in patients with NIDDM and, therefore, may have a
beneficial effect on fibrinolysis.
PMID- 9647335
TI - Influence of non-insulin-dependent diabetes mellitus on plasma endothelin-1
levels in patients with advanced atherosclerosis.
AB - Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen
properties. Increased circulating ET-1 levels were found in patients with
atherosclerosis as well as in patients with non-insulin-dependent diabetes
mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The
aim of the present study was to ascertain the influence of the NIDDM on plasma ET
1 levels in patients with advanced atherosclerotic lesions. The circulating ET-1
levels were measured in 16 NIDDM patients (68.4 +/- 8.4 years) with
macroangiopathy and in ten patients (65.3 +/- 11 years) with atherosclerosis
without NIDDM. Twenty-two healthy subjects (43.1 +/- 18.3 years) served as
controls. Circulating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8
pg/mL) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with vascular
disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No significant
relationship was found between age and ET-1 concentrations, and no differences
were noted between men and women in the control group. This study demonstrated
that circulating ET-1 levels are increased in patients with atherosclerosis and
that those with NIDDM showed the highest ET-1 levels. These observations strongly
support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest
that this peptide may be involved in the development of atherosclerotic lesions
in the NIDDM. We speculated that chronic exposure to hyperinsulinemia and
hypertriglyceridemia in the diabetic patients could account for the increased ET
1 levels found in these patients.
PMID- 9647336
TI - Relationship of microalbuminuria with the diabetic foot ulcers in type II
diabetes.
AB - Microalbuminuria is a significant risk factor associated with nephropathy,
retinopathy, and cardiovascular disease; however, there are no previous reports
on the relationship of microalbuminuria with diabetic foot ulcers or stroke,
despite the fact that microalbuminuria is a marker of vascular damage. The
purpose of this study was to determine the relationship of microalbuminuria with
diabetic foot ulcers in type II diabetes patients. In this, cross-sectional
clinical study, outpatients of the offices at first level medical care in
Durango, Mexico, were included in one of two groups; (a) patients with diabetic
foot ulcers and (b) control of group patients without diabetic foot ulcers.
Diabetic foot diagnosis was established on the basis of clinical criteria and
pletismography. Patients diagnosed with renal disease, urinary tract infection,
acute febrile illness, or heart failure and those receiving angiotensin
converting enzyme inhibitors were excluded from the study. Microalbuminuria was
measured, on a 24-h urine collection, by precipitation with sulfasalicylic acid,
and turbidity was determined by measuring absorbance with a spectrophotometer.
The study included 670 diabetic patients. Using both odds ratio and logistic
regression analyses, diabetes duration, cigarette smoking, aging, and
microalbuminuria showed a strong relationship with diabetic foot ulcers.
Microalbuminuria should be considered as an independent risk factor for diabetic
foot ulcers.
PMID- 9647337
TI - Impact of diabetes mellitus on infrainguinal bypass grafting.
AB - The purpose of this study was to examine the role of diabetes mellitus (DM) in
infrainguinal bypass graft outcome. One hundred forty-four patients who underwent
170 infrainguinal bypass grafts from 1990 to 1995 were reviewed retrospectively.
Seventy-eight patients (94 bypasses) had DM and were followed for an average of
15.4 months; 13 patients were lost to follow up. The mean age was 68 years; 44
(56.4%) were men. The major indication for intervention was limb salvage for the
DM (87/94, 92.6%) and non-DM (56/76, 73.7%) groups. No significant difference was
found for perioperative wound complications, hematoma, myocardial infarction, or
deep venous thrombosis between the DM and non-DM groups. Early mortalities were
three for DM and one for non-DM patients. No significant difference was found
between primary patency (p = 0.71), secondary patency (p = 0.32), limb salvage (p
= 0.99), and survival (p = 0.72) between DM and non-DM groups. DM patients were
more likely to have significant tissue loss (p = 0.009) and a longer hospital
stay (p = 0.01). In conclusion, infrainguinal vein bypass grafting can be
performed successfully in diabetic patients with comparable patency and limb
salvage rates to those without DM.
PMID- 9647338
TI - Effect of aldose reductase inhibition on cardiovascular reflex tests in patients
with definite diabetic autonomic neuropathy over a period of 2 years.
AB - The potential of the aldose reductase inhibitor tolrestat to ameliorate definite
diabetic autonomic neuropathy (DAN), as defined by standard cardiovascular
autonomic function tests, was evaluated in 35 patients over a period of 2 years,
with repeated measurements at 3-month intervals. The effect of tolrestat (200 mg
a day) was compared with that of placebo on 35 controls with diabetes mellitus,
of similar age, gender, and glycemic control. In the placebo group, a significant
deterioration of the indices, with the exception of Valsalva ratio, was recorded,
while tolrestat induced a significant beneficial change in the values of most
standard cardiovascular reflex tests, in comparison to baseline and placebo. The
deep breathing tests (expiration-inspiration ratio, standard deviation, and mean
circular resultant of R-R intervals), postural index, and postural hypotension
were favorably affected. Three of 35 patients on tolrestat (8.6%) developed high
transaminases levels (more than threefold the upper normal limit) and were
withdrawn from the study. In conclusion, tolrestat improved autonomic nervous
system function in patients with definite DAN, in comparison to baseline and
placebo. The clinical importance of this finding needs further investigation.
PMID- 9647339
TI - Long-term intraindividual variability of serum lipids in patients with type I and
type II diabetes.
AB - The objective of this study was to estimate the long-term intraindividual
variability of lipid levels in adult type I and type II diabetic patients. Total
cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low
density lipoprotein (LDL) cholesterol, and hemoglobin A1c were measured every 3-6
months in 135 patients attending the Austin Hospital diabetes clinic. Analysis
was performed on 60 diabetic patients (33 type I and 27 type II) who had not been
treated with lipid lowering drugs and who met the inclusion criteria of at least
five measurements [mean +/- standard error of the mean (SEM), 9.5 +/- 0.4; range,
5-17] collected over a minimum of 4 years (5.1 +/- 0.1; 4-6.5 years). Total
variability, expressed as coefficient of variation, was 8.8 +/- 0.4% for total
cholesterol, 23.9 +/- 1.5% for triglycerides, 10.2 +/- 0.5% for HDL cholesterol,
and 12.0 +/- 0.5% for LDL cholesterol. Biological variability, derived from total
and analytical variability, was higher than previous estimates in nondiabetic
subjects for total cholesterol and HDL cholesterol but similar for triglycerides
and LDL cholesterol. No relationship was observed between total lipid variability
and diabetes type, age, baseline or mean lipid levels, duration of follow-up, or
the number of samples per patient. Men demonstrated greater variability than
women for total cholesterol (men 9.5 +/- 0.5%, n = 34, women 7.9 +/- 0.5%, n =
26, p < 0.01) and triglycerides (men 26.5 +/- 2.2%, women 20.4 +/- 1.4%, p =
0.03). Total lipid variability was also unrelated to baseline or mean hemoglobin
A1c or to the change in hemoglobin A1c during the study as a whole. However, the
change in hemoglobin A1c was associated with the change in total cholesterol (r =
0.30, p < 0.03) and the change in LDL cholesterol (r = 0.27, p < 0.05). In
conclusion, long-term intraindividual lipid variability in adult diabetic
subjects is higher for total and HDL cholesterol than previously published values
in nondiabetic subjects. Variability of triglycerides is at least double that of
total cholesterol, HDL cholesterol and LDL cholesterol. Biological variability,
not measurement error, accounts for the greatest proportion of total variability
for all lipid parameters. Confidence levels calculated from these data have
implications for the initiation of lipid lowering therapy and in monitoring the
effects of intervention.
PMID- 9647340
TI - Abnormalities of small intestinal endocrine cells in non-obese diabetic mice.
AB - The endocrine cells in the duodenum of pre-diabetic and diabetic female non-obese
diabetic (NOD) mice aged 22-24 weeks were studied by means of
immunohistochemistry and computed image analysis as well as by radioimmunoassays
of tissue extracts. As controls, 12 female BALB/cJ mice of the same age as NOD
mice were used. The number of secretin-immunoreactive cells increased in diabetic
but not in pre-diabetic NOD mice. The level of extractable secretin was higher in
both pre-diabetic and diabetic NOD mice. The number of GIP-, CCK/gastrin-, and
serotonin-immunoreactive cells was significantly reduced in both pre-diabetic and
diabetic NOD mice. There was no statistical difference in the number of
somatostatin-immunoreactive cells between the NOD mice and controls. The level of
GIP was higher and gastrin was lower in NOD mice compared to controls. There was
no statistical difference in the somatostatin level between the NOD mice and
controls. The cell secretory index was elevated in all the endocrine cell types
except CCK/gastrin cells. It has been suggested that some of the changes in the
duodenal endocrine cells could be attributed to the diabetes state, but most of
the changes seem to take place before the onset of diabetes. The abnormalities in
the duodenal endocrine cells observed here in an animal model for diabetes type I
might have relevance for the gastrointestinal dysfunction displayed in human
diabetes.
PMID- 9647341
TI - A case of fatal rhinocerebral mucormycosis with new onset diabetic keto-acidosis.
PMID- 9647342
TI - The role of acarbose in the treatment of non-insulin-dependent diabetes mellitus.
AB - Acarbose is the first of a new class of antidiabetic agents, the alpha
glucosidase inhibitors. Acarbose has proven effectiveness as a first-line drug in
type 2 diabetes insufficiently controlled by diet alone. In addition to providing
short-term glycemic control, acarbose also reduces HbA1c levels. This effect is
greatest when therapy is initiated early in the disease and when baseline HbA1c
levels are high. Depending on the baseline HbA1c value, therapeutic doses of
acarbose lead to a HbA1c reduction of 0.5%-1.2%. Acarbose may be safely combined
with all oral hypoglycemic agents, and has been found to have utility as an
adjunct to sulfonylurea and metformin therapy. It also improves control of
insulin-treated type 2 diabetes and enables a reduction of exogenous insulin
requirements of up to 30%. Acarbose also has beneficial effects on the coronary
risk factors, e.g. postprandial triglyceride levels, elevated cholesterol, and
hyperinsulinemia. The early phase of acarbose therapy may be associated with side
effects such as meteorism, flatulence, and diarrhea. These result from the local
effect of the drug and decline with time. To date, there have been no reports of
systemic toxicity. Acarbose does not cause hypoglycemias or weight gain.
PMID- 9647343
TI - Genetic engineering of protein-based polymers: potential in controlled drug
delivery.
PMID- 9647344
TI - Oligopeptide transporters as putative therapeutic targets for cancer cells.
PMID- 9647345
TI - Intracellular phosphorylation of zidovudine (ZDV) and other nucleoside reverse
transcriptase inhibitors (RTI) used for human immunodeficiency virus (HIV)
infection.
AB - Dramatic reductions of viral load and increased survival have been achieved in
patients infected with the Human Immunodeficiency Virus (HIV) with the
introduction of combination antiretroviral therapy. Currently 11 agents including
nucleoside reverse transcriptase inhibitors (RTI), non-nucleoside RTI and
protease inhibitors are available for the use for treatment of HIV infection.
Recent studies have demonstrated that certain combinations of these drugs are
advantageous over their individual use as monotherapy with an even more sustained
viral suppression. Much emphasis has therefore been put on studies evaluating the
interactions of these different compounds. Especially the intracellular
metabolism of nucleoside RTI has been evaluated to some extent, by both in vitro
and in vivo studies. These compounds need to undergo phosphorylation to their
active 5'-triphoshates involving several enzymatic steps and the nucleoside
concentration in the plasma may not correlate with intracellular concentrations
of active drug. It is therefore of great importance to study these drugs at an
intracellular level in order to evaluate their efficacy. This review summarizes
the intracellular phosphorylation of Zidovudine and other nucleoside analogs
investigated by in vitro experiments and the efforts of measuring the active
anabolites in vivo in cells isolated from HIV infected patients on nucleoside
therapy.
PMID- 9647347
TI - The molecular mobility of supercooled amorphous indomethacin as a function of
temperature and relative humidity.
AB - PURPOSE: To determine the relaxation times of supercooled indomethacin as a
function of temperature and relative humidity above Tg, and to analyze the
results in the context of being able to predict such behavior at various storage
conditions. METHODS: Dielectric relaxation times were measured in the frequency
domain (12 to 10(5) Hz) for amorphous indomethacin equilibrated at 0, 56, and 83%
relative humidity. The heating rate dependence of Tg for dry supercooled
indomethacin was measured with differential scanning calorimetry and used to
determine relaxation times. The results were compared with previously published
shear relaxation times and enthalpy recovery data. RESULTS: Very good agreement
was observed between dielectric and shear relaxation times, and those obtained
from the heating rate dependence of the Tg, for dry indomethacin as a function of
temperature above Tg. The introduction of water lowered the dielectric relaxation
times of supercooled indomethacin without significantly affecting its fragility.
The relaxation times below Tg, found to be lower than those predicted by
extrapolation of the data obtained above Tg, were analyzed in the context of the
Adam-Gibbs-Vogel equation. CONCLUSIONS: The relaxation times of amorphous
indomethacin obtained from the heating rate dependence of Tg were in good
agreement with those obtained from shear and dielectric measurements, thus
validating a relatively simple approach of assessing molecular mobility. The
significant molecular mobility of amorphous indomethacin observed below Tg, and
the significant plasticizing effects of sorbed water, help to explain why
amorphous indomethacin crystallizes well below Tg over relatively short time
scales.
PMID- 9647346
TI - Recent advances in intestinal macromolecular drug delivery via receptor-mediated
transport pathways.
AB - Receptor-mediated transport mechanisms provide a pathway for the trafficking of
extracellular macromolecules into (endocytosis) and across (transcytosis) the
cell. This comprises the binding of a ligand to a specific cell-surface receptor,
clustering of the ligand-receptor complexes in endocytotic vesicles and vesicular
sorting. This review focuses on recent advances in cellular and molecular biology
pertaining to receptor-mediated endocytosis. A concise overview is presented of
current and potential future applications of targeting to RME mechanisms to
improve oral macromolecular drug delivery.
PMID- 9647348
TI - Bond cleavage reactions in solid aqueous carbohydrate solutions.
AB - PURPOSE: To investigate chemical reactivity in water soluble glasses. METHODS:
Rates of bond cleavage reactions in freeze-dried and freeze-concentrated aqueous
carbohydrate solutions were measured above and below the glass transition
temperatures (Tg). The kinetics of two reactions have been determined in
formulations containing di- and polysaccharides: (1) fission of the Asp-Pro
peptide bond in Physalaemin and Hamburger peptide by following the release of
proline, using a ninhydrin based reaction and (2) the unimolecular dissociation
of 2-(4-nitrophenoxy) tetrahydropyran by following the release of the 4
nitrophenoxy anion. RESULTS: The results show clearly that reaction occurs below
the glass transition temperature, albeit at very reduced rates. No significant
enhancement of the temperature dependence of the rate constant was observed near
Tg. Different water soluble glasses provide different degrees of stability. The
order of stabilisation was sucrose>Ficoll (low mol. weight)>Byco A approximately
equal to Ficoll (high mol. weight)>dextran. The density of the matrix, and
therefore the degrees of freedom of mobility of the reactant, is thought to be
responsible for these differences. CONCLUSIONS: The storage of therapeutic
agents, such as proteins, in glassy matrices below Tg does not confer indefinite
stability. When formulating products, notice should be taken of the differing
stabilisation properties of excipients.
PMID- 9647349
TI - Effects of pluronic block copolymers on drug absorption in Caco-2 cell
monolayers.
AB - PURPOSE: The present work characterizes the effects of Pluronic copolymers on the
transport of a P-gp-dependent probe, rhodamine 123 (R123) in Caco-2 cell
monolayers. METHODS: The accumulation and efflux studies were performed on the
confluent Caco-2 monolayers using fluorescent probes with and without Pluronic
copolymers. RESULTS: At concentrations below the critical micelle concentration
single chains ("unimers") of Pluronic P85 enhanced the accumulation and inhibited
the efflux of R123 in Caco-2 monolayers. The transport of the P-gp-independent
probe, rhodamine 110 was not altered under these conditions. In contrast the
micelles increased R123 accumulation to a much lower extent when compared to the
unimers and enhanced R123 efflux in Caco-2 monolayers. CONCLUSIONS: Pluronic P85
unimers increase accumulation of a P-gp-dependent drug in Caco-2 monolayers
through inhibition of the P-gp efflux system. The mechanism of the micelle effect
is not known, however, it is very similar to the micelle effects in BBMEC. This
has been previously shown to involve vesicular transport of the micelle
incorporated drug. The study suggests that Pluronic copolymers can be useful in
increasing oral absorption of select drugs.
PMID- 9647350
TI - Jejunal absorption and metabolism of R/S-verapamil in humans.
AB - PURPOSE: The purpose of this human intestinal perfusion study was to investigate
the transport and metabolism of R/S-verapamil in the human jejunum (in vivo).
METHODS: A regional single-pass perfusion of the jejunum was performed using a
Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200
min and was divided into two periods each of 100 min. The inlet concentrations of
verapamil were 4.0 and 40 mg/l in period one and two, respectively. RESULTS: The
effective jejunal permeability (Peff) of both R- and S-verapamil increased (p <
0.05) when the inlet concentration was increased consistent with saturation of an
efflux mechanism. However, both R- and S-verapamil had high intestinal Peff,
consistent with complete absorption. The Peff of antipyrine also increased, but
there was no difference in the Peff for D-glucose in the two periods. The
appearance of R/S-norverapamil in the intestinal perfusate leaving the jejunal
segment was non-linear, presumably due to saturation of the CYP3A4 metabolism.
CONCLUSIONS: The increased Peff in parallel with increased entering drug
concentration is most likely due to saturable efflux by P-glycoprotein(s) in the
human intestine.
PMID- 9647351
TI - Interaction of a self-emulsifying lipid drug delivery system with the everted rat
intestinal mucosa as a function of droplet size and surface charge.
AB - PURPOSE: To investigate the interaction of positively charged self-emulsifying
oil formulations (SEOF) following aqueous dilution as a function of resulting
emulsion droplet charge and size with rat everted intestinal mucosa, adherent
mucus layer and Peyer's patches, using cyclosporine A (CsA) as a lipophilic model
drug. METHODS: Droplet size determination (TEM technique) and zeta-potential
measurements were used to characterize the resulting emulsions. For the ex vivo
interaction study, the well-known rat intestine everted sac technique was used in
combination with confocal microscopy. RESULTS: The positively charged oil
droplets formed by SEOF dilutions at ratios of 1/50 and 1/10 elicited the
stronger interaction with the mucosal surface. The positive charge of the smaller
droplets was more readily neutralized, and even reversed in aqueous solutions
containing moderate subphysiological mucin concentrations. Parameters such as
droplet size, negativity of the epithelial mucosa potential and presence of the
mucus layer on the epithelial surface affected drug mucosa uptake and the
adhesion of the positively charged droplets to the rat intestinal mucosa.
CONCLUSIONS: The enhanced electrostatic interactions of positively charged
droplets with the mucosal surface are mostly responsible for the preferential
uptake of CsA from the positively charged droplets as compared to negatively
charged droplets irrespective of the experimental conditions used. The increased
uptake of the CsA from the negatively charged oil droplets was consistent with
the dilution extent, as expected, whereas in the positively charged droplets, an
intermediate droplet size range was identified resulting in optimum drug uptake
and clearly suggesting that drug uptake was not consistent with either dilution
extent or droplet size.
PMID- 9647352
TI - Nitric oxide donors enhance rectal absorption of macromolecules in rabbits.
AB - PURPOSE: The objective of this investigation is to evaluate the potential of
nitric oxide (NO) donors as a new class of absorption enhancers which may act on
intestinal epithelial cells through epithelial actions of the chemical mediator,
NO. METHODS: Suppositories containing NO donors and insulin were administered
into the rabbit rectum. After administration of the suppository, blood samples
were collected from the auricular vein. The plasma insulin and glucose
concentrations were determined. RESULTS: The NO donor S-nitroso-N-acetyl-DL
penicillamine (SNAP, 4 mg) induced a significant increase in the rate of insulin
absorption from the rectum. Administration of a suppository containing SNAP
without insulin affected neither the plasma insulin nor the plasma glucose
concentration. Other NO donors, NOR1 and NOR4, also induced increases in the
insulin absorption. The absorption enhancement effect of SNAP was inhibited by
coadministration of the NO scavenger carboxy-PTIO. SNAP also enhanced FITC
dextran (MW 4,000) absorption. Little cytotoxicity of SNAP (3.0 mg/ml) as
assessed in terms of the rate of lactate dehydrogenase (LDH) release from Caco-2
cells was detected for 2 h of incubation. CONCLUSIONS: These findings suggest
that NO enhanced macromolecular absorption from the rectum without mucosal cell
damage, and that NO donors can act as potent absorption enhancers.
PMID- 9647353
TI - Pharmacokinetics of the transdermal reservoir membrane system delivering beta
estradiol: in vitro/in vivo-correlation.
AB - PURPOSE: The aim of our study was to investigate the high fluctuations of
Estradiol (E2) plasma levels transdermally delivered in postmenopausal women by a
commercially available membrane controlled reservoir system (MCRS). METHODS: The
transdermal E2 flux either out of a complete MCRS or across its membrane out of
defined ethanol water mixtures was determined, as well as E2 plasma profiles in 6
postmenopausal women produced by a MCRS. RESULTS: The transdermal in vitro E2
flux rate out of a complete MCRS, claimed to deliver 25 microg/day, increased
steadily, reaching a maximum value of 2.06 +/- 0.58 microg/h at 30 to 40 hours
and decreased to a rate of about 0.5 microg/h from 60 to 90 hours. No
statistically significant differences between plasma profiles calculated from the
in vitro investigation and derived from a clinical study could be identified. The
E2 flux in defined ethanol/water mixtures across MCRS-membrane, adhesive and skin
layer increased with increasing ethanol concentrations up to a maximum of 227 +/-
34 ng/cm2/h at an ethanol concentration of 62.5% (V/V) and decreased with further
increase in the volume fraction of ethanol. CONCLUSIONS: In vitro as well as in
vivo investigations showed high fluctuation of E2 plasma profiles in
postmenopausal women produced by the MCRS. These fluctuations are caused by a non
constant input rate of E2 which may be due to changing ethanol concentrations in
the reservoir of the MCRS.
PMID- 9647354
TI - Skin mini-erosion sampling technique: feasibility study with regard to serial
glucose measurement.
AB - PURPOSE: To describe a dermally non-invasive serial sampling technique and to
test its clinical feasibility with regard to glucose measurement. METHODS: A
standardized skin mini-erosion devoid of the epidermal barrier, and covered by an
artificial one, was formed by a suctioning technique. Interstitial fluid (IF) was
extracted serially by brief application of negative pressure, and its glucose
content compared with that in capillary or venous blood samples. RESULTS: The
procedure caused no discomfort. The epidermis regenerated rapidly after
experimentation. There were no complications. In non-diabetic subjects (n = 13)
the mean of all IF values measured daily for 6 days was 6.2 +/- 0.1 mmol/l (+/
SE). The corresponding capillary blood glucose value was 5.6 +/- 0.1 mmol/l, and
the venous glucose value was 5.4 +/- 0.1 mmol/l. The differences between IF
glucose values and invasive control values remained within narrow limits
throughout. The 2SD limits of agreement for the differences were 1.44 mmol/l (IF
vs. capillary blood samples) and 1.76 mmol/l (IF vs venous samples) respectively.
The OGTT curves suggested glucose kinetics to be similar in IF and in capillary
blood. In diabetic subjects, the mean of IF values determined serially during one
day was 15.3 +/- 1.0 mmol/l (range, 6.7-21.8 mmol/l), and the corresponding mean
capillary value was 12.0 +/- 0.9 mmol/l (range, 3.3-17.2 mmol/l). The ICC for all
paired photometric observations was 0.948. CONCLUSIONS: The results suggest the
new sampling technique to be a feasible approach for clinical and experimental
purposes. A functionally integrated sampling patch is entering the clinical
testing stage.
PMID- 9647355
TI - In vitro dissolution profile comparison--statistics and analysis of the
similarity factor, f2.
AB - PURPOSE: To describe the properties of the similarity factor (f2) as a measure
for assessing the similarity of two dissolution profiles. Discuss the statistical
properties of the estimate based on sample means. METHODS: The f2 metrics and the
decision rule is evaluated using examples of dissolution profiles. The confidence
interval is calculated using bootstrapping method. The bias of the estimate using
sample mean dissolution is evaluated. RESULTS: 1. f2 values were found to be
sensitive to number of sample points, after the dissolution plateau has been
reached. 2. The statistical evaluation of f2 could be made using 90% confidence
interval approach. 3. The statistical distribution of f2 metrics could be
simulated using 'Bootstrap' method. A relatively robust distribution could be
obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was
found to reduce the bias. CONCLUSIONS: The similarity factor f2 is a simple
measure for the comparison of two dissolution profiles. But the commonly used
similarity factor estimate f2 is a biased and conservative estimate of f2. The
bootstrap approach is a useful tool to simulate the confidence interval.
PMID- 9647356
TI - Effect of experimental diabetes mellitus and arthritis on the pharmacokinetics of
hydroxychloroquine enantiomers in rats.
AB - PURPOSE: To study the effect of experimental diabetes and arthritis on the
pharmacokinetics of hydroxychloroquine (HCQ) enantiomers in rats. METHODS: The
pharmacokinetic studies were carried out following administration of 40 mg/kg of
racemic HCQ to diabetic, insulin-treated diabetic, adjuvant arthritic and control
rats. RESULTS: Renal (70% and 62% for R- and S-HCQ, respectively) and non-renal
clearance (100% and 145% for R- and S-HCQ, respectively) of HCQ enantiomers were
significantly increased in diabetic rats. Diabetes-induced alterations in the
disposition of HCQ were reversed by insulin treatment. In arthritic rats,
systemic clearance (CL) of HCQ enantiomers was significantly reduced (1.05 +/-
0.15 and 1.3 +/- 0.19 l/h/kg for R- and S-HCQ, respectively) compared to controls
(1.69 +/- 0.32 and 1.93 +/- 0.34 l/h/kg for R- and S-HCQ, respectively). The
fraction unbound of the R- and S-HCQ were 49.4% and 50.5% lower in platelet rich
plasma of arthritic rats compared to healthy rats. Increased blood concentrations
of HCQ enantiomers in arthritic rats were significantly related to the degree of
inflammation. CONCLUSIONS: Diabetes significantly increased the CL of both R- and
S-HCQ by increasing renal and non-renal clearance. Arthritis caused a significant
decrease in CL of HCQ enantiomers through increased binding and a decreased
intrinsic clearance. The effect of the diseases on the pharmacokinetics of HCQ,
however, was not stereoselective.
PMID- 9647357
TI - Pharmacokinetics and biodistribution of a nucleotide-based thrombin inhibitor in
rats.
AB - PURPOSE: To characterize the pharmacokinetic and tissue distribution profiles of
a nucleotide-based thrombin inhibitor (GS522, phosphodiester oligonucleotide,
GGTTGGTGTGGTTGG) following intravenous administration to rats. METHODS:
Pharmacokinetic study: 10 mg/kg, 20 mg/kg, 30 mg/kg (6 animals/dose) were
administered to rats by rapid injection into the femoral vein. Blood samples were
collected over a 45 minute period. Plasma concentrations of GS522 were determined
using capillary gel electrophoresis with laser-induced fluorescence detection.
Biodistribution Study: 10 mg/kg (400 microl, 31.46 microCi/ml) of 3H-GS522 was
administered to rats by rapid injection into the femoral vein. The animals were
sacrificed by decapitation at 1, 5, 10, 30, 60, 360 minutes post-dose (3
rats/point). Brain, blood, duodenum, eyes, heart, kidney, liver, lungs, muscle,
pancreas, skin, spleen and vein samples were collected, processed and quantitated
using liquid scintillation counting. RESULTS: The pharmacokinetic profile
declines in multiexponential manner, exhibiting extremely fast distribution and
elimination (t1/2 = 7.6-9.0 min, Cl = 22.0-28.0 ml/min, V = 83.9-132.4 ml/kg).
GS522 follows linear pharmacokinetics, with the area under the curve being
proportional to the dose (Rsq = 0.9744). Highest radioactivity levels were
detected in kidney, liver and blood (39.7, 15.7 and 15.3% dose/ respective
organ). Less than 1% of the dose was detected in the heart, spleen and lungs, and
>0.3% of the dose was found in the brain and eyes. The oligonucleotide associated
radioactivity was uniformly distributed between the brain regions (left and right
lobe and cerebellum). Six hours following the dose administration a statistically
significant increase (p < 0.05) in radioactivity levels was observed in the
brain, eyes, skin, liver, pancreas and vein. CONCLUSIONS: The pharmacokinetic and
biodistribution profiles of GS522 following intravenous administration to rats at
three doses were characterized. The oligonucleotide associated radioactivity was
widely distributed in tissues. The amount of radioactivity sharply decreased with
time in most tissues. Kidney, liver and muscle were the main sites of
accumulation. The oligonucleotide associated radioactivity did not cross the
blood brain barrier to an appreciable extent. In addition, a statistically
significant increase (p < 0.05) in the radioactivity levels observed in select
tissues suggested a re-uptake mechanism for intact oligonucleotide or its
degradation products.
PMID- 9647358
TI - Receptor occupancy in myocardium, adrenal cortex, and brain by TH-142177, a novel
AT1 receptor antagonist in rats, in relation to its plasma concentration and
hypotensive effect.
AB - PURPOSE: To study the relationship between angiotensin II (AII) receptor
occupancy ex vivo in tissues plasma concentration and hypotensive effect of a
novel AII receptor antagonist, TH-142177 and losartan in rats. METHODS: At 2, 8
and 24 hr after oral administration of TH-142177 and losartan in rats, AII
receptors in myocardium, adrenal cortex and cerebral cortex were determined by
radioligand binding assay using [125I]Sar1,Ile8-AII. Plasma concentrations of
both drugs and metabolite in rats were also measured using validated HPLC assays.
Further, systolic blood pressure (SBP) in conscious renal hypertensive rats
treated orally with TH-142177 and losartan were measured by using a tail cuff
plethysmographic method. RESULTS: Oral administration of TH-142177 (1.8 and 5.5
micromol/kg) and losartan (6.5 and 21.7 micromol/kg) in rats brought about dose
dependent decreases in [125I]Sar1,Ile8-AII binding sites (Bmax) in myocardium and
adrenal cortex. The extent of receptor occupancy by both drugs in adrenal cortex
was maximal at 2 hr later but that in myocardium at 8 hr later. Further, the
receptor occupancy was more sustained in myocardium than adrenal cortex. The ex
vivo binding affinity of TH-142177 for AII receptors in these tissues was roughly
three times higher than that of losartan. Also, cerebral cortical [125I]Sar1,Ile8
AII binding was significantly reduced by oral administration of losartan but not
by TH-142177. The time course of AII receptor occupancy by both drugs in adrenal
cortex appeared to be in parallel with that of their plasma concentrations, while
the time course in myocardium correlated with that of their hypotensive effects
rather than plasma concentrations. CONCLUSIONS: TH-142177 produced a relatively
selective and sustained occupancy ex vivo of AII receptors in myocardium and
adrenal cortex of rats with approximately three times greater potency than
losartan. Its time course of myocardial receptor occupancy was in parallel with
that of hypotensive effect rather than plasma concentration.
PMID- 9647359
TI - Non-invasive assessment and control of ultrasound-mediated membrane
permeabilization.
AB - PURPOSE: Ultrasound has been shown to transiently permeabilize biological
membranes, thereby facilitating delivery of large compounds such as proteins and
DNA into cells and across tissues such as skin. In this study, we sought to
quantitatively determine the dependence of cell membrane permeabilization on
ultrasound parameters and to identify acoustic signals which correlate with
observed membrane permeabilization. METHODS: Bovine red blood cells were exposed
to ultrasound at 24 kHz over a range of controlled conditions. The degree of
membrane permeabilization was measured by release of hemoglobin and was
determined as a function of ultrasound parameters and measured acoustic signals.
RESULTS: These studies showed that permeabilization increased with incident
ultrasound pressure, increased with total exposure time above a threshold of
approximately 100 msec, showed a weak dependence on pulse length with a small
maximum at 3 msec, and did not depend on duty cycle under the conditions
examined. Using measured acoustic spectra we found that red blood cell membrane
permeabilization correlated best with the pressure measured at half the driving
frequency (f/ 2 = 12 kHz) and its ultraharmonics, less strongly with the
broadband noise pressure measured between peaks, and least strongly with pressure
measured at the driving frequency and its higher harmonics. Permeabilization
caused by ultrasound applied at any set of conditions tested in this study could
be well predicted by the parameter tau x Pf/2, which characterizes the total
cavitational exposure. CONCLUSIONS: This study provides a quantitative guide to
designing ultrasound protocols useful for drug delivery. The acoustic
measurements support the hypothesis that ultrasonic cavitation is the mechanism
by which membranes are permeabilized. They also suggest that measurable acoustic
signals can provide noninvasive, real-time feedback about membrane
permeabilization and drug delivery.
PMID- 9647360
TI - Mechanistic studies on effervescent-induced permeability enhancement.
AB - PURPOSE: To determine the mechanism(s) by which effervescence induces penetration
enhancement of a broad range of compounds ranging in size, structure, and other
physiocochemical properties across rat and rabbit small intestinal epithelium.
METHODS: Effervescent induced penetration enhancement was investigated in vitro
by utilization of a modified Ussing chamber diffusion cell apparatus and in vivo
by single-pass intestinal perfusion. RESULTS: Carbon dioxide (CO2) bubbling
directly onto rabbit ileum epithelium induced an increase in drug permeability.
Mechanistic studies indicated that effects due to CO2 bubble evolution, such as
increased drug dissolution rates, mucus thinning/stripping, and pH buffer effects
did not contribute to increases in drug flux. Cellular enzyme (5'-ND and LDH) and
total protein release assays did not indicate cell membrane perturbation and/or
damage. CO2 bubbling induced a reduction in transepithelial electrical resistance
(TEER) indicating epithelial disruption due to a structural change of the
paracellular pathway. This was further substantiated by a MW dependence on
paracellular marker flux. In addition, tissue recovery was relatively rapid,
approximately 20 min. CONCLUSIONS: CO2 bubbling directly onto the intestinal
epithelium induced enhanced drug permeability due to an alteration of the
paracellular pathway. This, in addition to fluid flow and membrane hydrophobicity
concepts, may account for observed increases in drug flux.
PMID- 9647361
TI - Triazene drug metabolites: part 15. Synthesis and plasma hydrolysis of anticancer
triazenes containing amino acid carriers.
AB - PURPOSE: The synthesis of chemically stable triazene prodrugs capable of
hydrolysing under physiological conditions to liberate cytotoxic
monomethyltriazene alkylating agents. METHODS: A series of 3-aminoacyl-1-aryl-3
methyltriazenes was synthesised through reaction of 1-aryl-3-methyltriazenes with
N-BOC protected amino acids using the DCC method of activation, followed by
deprotection of the amino function using HCl in nitromethane. Half-lives for the
hydrolysis of these compounds to the corresponding monomethyltriazenes at 37
degrees C in isotonic phosphate buffer and in 80% human plasma containing 20%
phosphate buffer were determined by HPLC. RESULTS: The aminoacyltriazene prodrugs
hydrolyse in isotonic phosphate buffer with t1/2 values ranging from 26 to 619
minutes. In human plasma, several decompose at the same rate as in phosphate
buffer whereas those containing more lipophilic groups decompose more slowly. A
beta-alanyl derivative was found to be more stable in phosphate buffer (t1/2 =
180 minutes) than in plasma (t1/2 = 53 minutes). An N-acetylated alpha-alanyl
derivative was found to be chemically stable in phosphate buffer (t1/2 = 10
hours) but liberated the cytotoxic drug in t1/2 = 41 minutes in plasma,
demonstrating its ability to act as a substrate for plasma enzymes. CONCLUSIONS:
Aminoacyltriazenes are prodrugs of the antitumour monomethyltriazenes hydrolysing
in human plasma with a range of reactivities. The acylation of the alpha-amino
group seems to be an effective and simple means of reducing the chemical
reactivity of the alpha-aminoacyl derivatives while retaining a rapid rate of
enzymatic hydrolysis.
PMID- 9647362
TI - LC-UV-electrospray-MS-MS mass spectrometry analysis of plant constituents
inhibiting xanthine oxidase.
AB - PURPOSE: A previous screening showed that Amyema scandensi [corrected] Danser
(Loranthaceae) efficiently inhibited XOD. The aim of this study was to identify
the compounds with anti-XOD properties. For this purpose, Electrospray Tandem
Mass Spectrometry (ESI-MS-MS) coupled with UV and Diode Array LC techniques were
employed. METHODS: Leaves were delipidized with petroleum ether and extracted
with acetone:water 70:30, v:v. The extract was fractionated into the ethyl
acetate and water soluble phases. Chemical investigation was performed following
the bioactivity guided fractionation. Two fractions with anti-XOD activity were
isolated by silica gel column chromatography of the ethyl acetate phase and
analyzed by LC-UV-ESI-MS-MS. RESULTS: The compounds identified with authentic
standards were: catechin, epicatechin, epicatechin-3-gallate, quercetin-3-O
glucoside, quercetin-3-O-rhamnoside, and isorhamnetin-3-O-glucoside. Other
constituents, only partially characterized, were a procyanidin dimer, a
procyanidin trimer, three dimers epi/catechine-epi/catechine gallate and
isorhamnetin-O-deoxyhexose. The anti-XOD activity was mainly due to galloyl
containing oligomeric proanthocyanidins. CONCLUSIONS: The coupling of UV Diode
Array-HPLC with ESI-MS-MS represents a versatile tool for the rapid
characterization of compounds in complex mixtures, avoiding time-consuming
previous isolation.
PMID- 9647363
TI - Development of infrared imaging to measure thermogenesis in cell culture:
thermogenic effects of uncoupling protein-2, troglitazone, and beta-adrenoceptor
agonists.
AB - PURPOSE: Although the effects of thermogenic agents in cell culture can be
measured by direct microcalorimetry, only a few samples can be analyzed over
several hours. In this report, we describe a robust non-invasive technique to
measure real-time thermogenesis of cells cultured in microtiter plates using
infrared thermography. METHODS: Yeast were transformed with uncoupling protein-2
(UCP2) or exposed to carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP)
or rotenone. Adipocytes were exposed to rotenone, FCCP, cycloheximide.
troglitazone, or CL316243. Thermogenesis was measured using infrared
thermography. RESULTS: Thermogenesis increased after exposing yeast to the
mitochondrial uncoupler, FCCP, or transforming the cells with UCP2. Further,
thermogenesis in adipocytes was stimulated by CL316243, a beta3-adrenoceptor
agonist being developed to treat obesity. The protein synthesis inhibitor,
cycloheximide, did not inhibit CL316243-mediated thermogenesis. In contrast, the
mitochondrial proton transport inhibitor, rotenone, inhibited thermogenesis in
yeast and adipocytes. Similarly, the antidiabetic agent, troglitazone, suppressed
thermogenesis in adipocytes. Although increased UCP synthesis resulted in
increased thermogenesis in yeast, UCP expression did not correlate with
thermogenesis in adipocytes. CONCLUSIONS: The results, taken together with the
high resolution (0.002 degrees C) and robustness (384-well format) of the
approach, indicate infrared-imaging is a rapid and effective method for measuring
thermogenesis in vitro.
PMID- 9647364
TI - Intestinal absorption of ribavirin is preferentially mediated by the Na+
nucleoside purine (N1) transporter.
PMID- 9647365
TI - Absorption of propranolol in humans following oral, jejunal, and ileal
administration.
PMID- 9647366
TI - Endoscopic ultrasonography versus cholangiography for the diagnosis of
choledocholithiasis.
AB - BACKGROUND: Choledocholithiasis is a major source of morbidity among patients
undergoing cholecystectomy for symptomatic gallstones. There is no consensus on
the best approach to diagnosing bile duct stones. We compared the safety,
accuracy, diagnostic yield, and cost of EUS- and ERCP-based approaches. METHODS:
Sixty-four consecutive pre- and post-cholecystectomy patients referred for
endoscopic retrograde cholangiopancreatography (ERCP) for suspected
choledocholithiasis were prospectively evaluated in a blinded fashion. All were
stratified into risk groups using predefined criteria. Endoscopic ultrasonography
(EUS) and ERCP were sequentially performed by two endoscopists. RESULTS: The
success rates of EUS and ERCP were 98% and 94%, respectively. The accuracy of EUS
for diagnosing choledocholithiasis was 94%. EUS provided an additional or
alternative diagnosis to bile duct stones in 21% of patients. The complication
rate of EUS was significantly lower than diagnostic ERCP. An EUS-based strategy
costs less than diagnostic ERCP in patients with low, moderate, or intermediate
risk. CONCLUSIONS: EUS is comparably accurate, but safer and less costly than
ERCP for evaluating patients with suspected choledocholithiasis. It is useful in
patients with an increased risk of having common bile duct stones based on
clinical criteria and those with contraindications for or prior unsuccessful
ERCP. EUS may enable selective performance of ERCP and improve the cost
effectiveness of diagnosing choledocholithiasis.
PMID- 9647367
TI - Does endoscopy have a positive impact on quality of life in dyspepsia?
AB - BACKGROUND: It is unclear whether normal endoscopy results in patients
investigated for dyspepsia has therapeutic value. Therefore the aim of this study
was to evaluate the effect of the endoscopy on quality of life and dyspeptic
symptoms. METHODS: One hundred ninety-six symptomatic patients (85 men and 111
women, mean age 42.9 years), who were receiving no treatment, were investigated
before and 1 week after endoscopy with the use of a battery of validated
questionnaires. RESULTS: Before endoscopy the health-related quality of life was
compromised in comparison with a normal population, but 1 week after a negative
endoscopy it is increased to a level which was close to the normal range despite
no major change in symptoms. Physical activity and sleep scores improved
significantly after endoscopy. CONCLUSION: The present results suggest that a
negative endoscopy improves quality of life in the short-term in patients with
dyspepsia, even though symptoms may persist.
PMID- 9647368
TI - Placebo-controlled trial assessing the use of oral midazolam as a premedication
to conscious sedation for pediatric endoscopy.
AB - BACKGROUND: This study was performed to evaluate the effect of midazolam, as
premedication before intravenous conscious sedation, on preprocedural,
procedural, and post-procedural patient comfort and anxiety in children
undergoing endoscopy. METHODS: A placebo-controlled, double-blind, randomized
study was conducted in 123 children (age 7.75 +/- 4.46 years, 56% male) using
oral midazolam (0.5 mg/kg, maximum 20 mg) as a premedication before insertion of
an intravenous access device (i.v.) and upper endoscopy. Patients were evaluated
with regard to changes in vital signs, level of sedation during i.v. placement,
level of pre- and post-procedure conscious sedation, ease of separation from
parents, ease and duration of procedure, recovery time, and amnesia to objects
shown before i.v. placement and immediately before the start of the procedure.
RESULTS: A significant difference was noted in the study group for the following
parameters: level of sedation for i.v. placement (p < 0.0001), pre-procedural
sedation (p < 0.001), ease of i.v. insertion (p < 0.003), ease of separation from
parents (p = 0.022), and ease of the nursing personnel's ability to monitor the
patient during the procedure (p = 0.0012). The patient's amnesia to an object
shown immediately before beginning the endoscopy was increased (p < 0.001).
Patients and parents were also more satisfied with the procedure process (p <
0.05). No significant difference was noted with regard to the length or
performance of the procedure or recovery time or in the dose of i.v. medication
required for successful completion of the endoscopy. CONCLUSION: Oral midazolam
is an effective and safe premedication for children undergoing upper endoscopy
and should be used in all anxious children and in patients previously judged to
be difficult to sedate.
PMID- 9647369
TI - A prospective endoscopic study of scalloped folds and grooves in the mucosa of
the duodenum as signs of villous atrophy.
AB - BACKGROUND: Scalloping of the valvulae conniventes visible at endoscopy may
predict the presence of villous atrophy. This prospective study was designed to
discover how commonly duodenal mucosal scallops and grooves occurred and to
delineate their relationship to villous atrophy. METHODS: All patients undergoing
upper gastrointestinal endoscopy by a single observer over 5 years were included.
After inspection of the duodenal mucosa, biopsy samples were taken from those in
whom the mucosa was abnormal (n = 26) and from those in whom it was not, but
where biopsy was indicated (n = 100). RESULTS: None of the 100 endoscopically
normal controls had subtotal villous atrophy: 94 had normal histology, 2 had non
atrophic change, and 4 had partial villous atrophy; 14 of the 26 individuals
(54%) with abnormal duodena had subtotal villous atrophy, 7 having both scallops
and grooves. Four had scallops alone, and three had grooves only. All patients
with both scallops and grooves had subtotal villous atrophy (100%), the positive
predictive value of which was 36% for scallops alone and 38% for grooves alone.
CONCLUSIONS: Scallops and grooves together indicate that subtotal villous atrophy
is very likely histologically, even when that diagnosis has not been suspected. A
normal duodenum excludes it.
PMID- 9647370
TI - Endoscopic resection of small duodenal carcinoid tumors with strip biopsy
technique.
AB - BACKGROUND: Most cases of duodenal carcinoid have conventionally been treated by
surgical resection. The aim of our study was to explore the feasibility of
endoscopic resection in small duodenal carcinoids. METHODS: The study population
consisted of seven patients with small duodenal carcinoids. The diagnosis was
confirmed by preoperative biopsies. The depth of tumor invasion was evaluated by
endosonography. RESULTS: The carcinoid was detected by endosonography in all
cases. Size ranged ultrasonographically from 1.5 mm to 7 mm. Tumor invasion was
confined to the submucosa in all patients. Endoscopic resection was performed
with the strip biopsy technique using a two-channel endoscope. In six patients,
the specimens were resected without severe complications. Five of them were
confirmed histologically to be typical carcinoids. In one patient, carcinoid was
not detected histologically in the specimen. In the remaining patient, a
perforation occurred. However, the huge ulcer was managed conservatively. Follow
up endoscopy revealed no evidence of recurrent or residual tumor in any patient.
CONCLUSION: Small duodenal carcinoids confined to the submucosa can be resected
endoscopically and preoperative endosonography is necessary for the determination
of endoscopic resectability.
PMID- 9647371
TI - Dilated common channel syndrome: endoscopic diagnosis, treatment, and
relationship to choledochocele formation.
AB - BACKGROUND: Choledochoceles (type III biliary cysts) are cystic dilations of the
terminal common bile duct or common pancreatobiliary channel. Although no size
criteria have been defined, it is generally assumed these must be large. However,
we describe patients who do not meet the perceived size criteria for
choledochoceles, but who nonetheless have a dilated common pancreatobiliary
channel. METHODS: We reviewed the presenting symptoms, endoscopic and
radiographic findings, and response to endoscopic therapy of patients meeting our
criteria for the dilated common channel syndrome. RESULTS: Of 2847 patients
undergoing ERCP, 100 (3.5%) had the dilated common channel syndrome. Common
presenting symptoms and signs included abdominal pain in 97%, abnormal liver
function test(s) in 66%, and a history of acute or recurrent pancreatitis in 46%.
A bulge was visible above the papilla in 88%, with a dilated common bile duct in
54% and a dilated pancreatic duct in 28%. After endoscopic unroofing of the
common channel, 77% had complete and long-lasting resolution of symptoms, 18% had
partial or transient improvement, and 5% had no change. CONCLUSIONS: Although
classic choledochoceles are rare, a lesser degree of dilation of the common
channel is more frequent than generally appreciated. We postulate that this
finding represents an "incomplete," acquired form of choledochocele, possibly
caused by underlying papillary stenosis. Whatever the etiology and appropriate
term, the presence of a dilated common channel predicts a high rate of clinical
response to endoscopic therapy.
PMID- 9647372
TI - Relative contribution of Ki-ras gene analysis and brush cytology during ERCP for
the diagnosis of biliary and pancreatic diseases.
AB - BACKGROUND: Ki-ras mutation analysis from material collected during ERCP has been
claimed to improve the diagnosis of pancreatic and bile duct carcinomas as
compared with conventional cytology. Our aim was to study the relative
contribution of both Ki-ras analysis and brush cytology in patients with a
significant stricture at ERCP. METHODS: Brushings were collected in duplicate for
both analyses in 142 patients in whom a definitive diagnosis was obtained by
histology or a minimal follow-up of 6 months. RESULTS: For pancreatic strictures,
sensitivity, specificity, and accuracy of Ki-ras analysis vs. cytology in
detecting malignancy were 81% vs. 66%, 72% vs. 100%, and 70% vs. 74%,
respectively. For biliary strictures, they were 25% vs. 42%, 100% vs. 100%, and
35% vs. 43%, respectively. The combination of the two methods only marginally
increased their sensitivity and accuracy in both types of strictures. CONCLUSION:
Ki-ras analysis is a sensitive method for diagnosing pancreatic but not biliary
carcinoma. However, its specificity is lowered by a high frequency of Ki-ras
mutations in patients with chronic pancreatitis (25%) who did not manifest cancer
development within a 6-month follow-up period. In pancreatic duct strictures,
brush cytology appears to be more specific in detecting malignancy; specificity
for Ki-ras and cytology are equivalent for the diagnosis of malignant bile duct
strictures. Therefore, making a clinical decision on the sole basis of Ki-ras
analysis is probably not justified in the majority of the cases.
PMID- 9647373
TI - Endoscopic retrieval of proximally migrated biliary and pancreatic stents:
experience of a large referral center.
AB - BACKGROUND: Proximal migration of a biliary or pancreatic stent is an infrequent
event but its management can be technically challenging. METHODS: Review of all
cases of proximally migrated biliary and pancreatic stents over a 10-year period
at a referral pancreatic-biliary center. Data abstracted from patient records
included indication for stenting, method of presentation, success of attempt, and
method used. Successful methods were determined by reviewing procedure reports.
Follow-up was attempted in all patients in whom stent retrieval had failed.
RESULTS: Thirty-three proximally migrated bile duct stents, and 26 proximally
migrated pancreatic duct stents were identified. Most of the patients were
without symptoms. Eighty-five percent of common bile duct stents and 80% of
pancreatic duct stents were successfully extracted endoscopically. Seventy-one
percent (34 of 48) were retrieved with a basket or balloon. Of the stents not
retrieved, two patients did not return for repeat ERCP, three patients with
malignant common bile duct strictures were managed with placement of a second
stent, three patients with pancreatic duct stents have remained without symptoms
with no further retrieval attempts, and three patients with proximally migrated
pancreatic duct stents required surgery because of pain and failure of multiple
endoscopic retrieval attempts. CONCLUSION: Over 80% of proximally migrated bile
duct and pancreatic duct stents may be extracted endoscopically. Few patients
will require surgery.
PMID- 9647374
TI - ERCP in the management of pediatric pancreatitis.
AB - BACKGROUND: Although ERCP is commonly performed in children, the effect of
findings at ERCP on the subsequent management of pediatric pancreatitis is
unknown. METHODS: We retrospectively reviewed charts to determine the impact of
ERCP on the management of recurrent acute or chronic pancreatitis in 17
consecutive children (3 boys and 14 girls, 3 to 16 years, mean 11.2 years) with
recurrent acute (n = 13) or chronic pancreatitis (n = 4) who underwent ERCP.
Radiographs were reviewed in a blinded manner, and the effect of ERCP findings on
subsequent management was determined. RESULTS: In 16 of 17 patients (94%), the
pancreatic duct was successfully visualized. Of the 16 studies, 9 (56%) had
abnormal findings. A change in therapy occurred in all 9 patients as a result of
the findings at ERCP. Of the 7 patients with a prior abnormal CT or ultrasound, 5
(71%) had an abnormal ERCP, all resulting in a change in therapy. Three of the 9
patients (33%) without radiographic abnormalities had an abnormal ERCP that, in
each case, resulted in a change in therapy. Overall, findings at ERCP altered
therapy in 52% of pediatric patients studied with recurrent acute or chronic
pancreatitis. A prior abnormal CT had a high predictive value with respect to
ERCP resulting in a change in management (83%). CONCLUSIONS: ERCP is useful in
the management of pediatric recurrent acute or chronic pancreatitis;
abnormalities are found at a rate similar to those found in adults.
PMID- 9647375
TI - Ineffective use of a detachable snare for colonoscopic polypectomy of large
polyps.
AB - BACKGROUND: Colonoscopic polypectomy of large polyps may be associated with
complications such as bleeding. Use of a detachable snare may reduce the risk of
bleeding. We describe several instances in which the use of such a device proved
to be ineffective. METHODS: A detachable snare was used for colonoscopic
polypectomy of large polyps in 18 patients (20 polyps), also applied at the
residual stalk after conventional polypectomy in 5 patients (5 polyps), and
evaluated retrospectively. RESULTS: Sixteen of the 20 polyps were pedunculated,
and 4 were semi-pedunculated. In 3 of the 4 semi-pedunculated lesions, the loop
slipped off after polypectomy because the lesions were cut close to the site of
encirclement. Bleeding occurred in 4 cases because of transection by the loop of
a thin stalk (4 mm) before polypectomy (1), slipping of the loop in a semi
pedunculated lesion (1), or insufficient tightening of the loop (2). After
conventional polypectomy, we could not effectively snare the residual stalk
because of flattening in 3 of the 5 lesions. CONCLUSIONS: Use of the detachable
snare for polypectomy of thin stalked or semi-pedunculated lesions may result in
technical failure of this technique. The stalk should be fully encircled with the
snare before polypectomy. The detachable snare is difficult to apply at the
residual stalk after conventional polypectomy.
PMID- 9647376
TI - Current laparoscopic gastrointestinal surgery.
PMID- 9647377
TI - Acetic acid improves identification of remnant islands of Barrett's epithelium
after endoscopic therapy.
AB - BACKGROUND: Instillation of acetic acid onto the uterine cervix at colposcopy has
been used for many years to highlight dysplastic areas and thereby enhance the
ability to obtain targeted biopsy specimens. As part of an ongoing trial of
multipolar electrocoagulation for Barrett's esophagus, we sought to develop a
simple technique to identify small islands of residual specialized columnar
epithelium after treatment. METHODS: In 21 consecutive patients, 5 to 10 mL of
1.5% acetic acid was sprayed onto the distal esophagus using a spray catheter,
followed immediately by spraying 50 mL of tap water. RESULTS: Initially, a
whitish coloration developed in both esophageal and gastric epithelia. After 2 to
3 minutes, the esophageal squamous mucosa remained white but the columnar
epithelium became reddish. Remnant islands of Barrett's epithelium were outlined
by a white rim. CONCLUSION: Acetic acid instillation enhances the ability to
detect small or indistinguishable remnant islands of columnar epithelium after
endoscopic treatment of Barrett's esophagus. This method is safe, rapid, and
inexpensive.
PMID- 9647378
TI - High-resolution cross-sectional imaging of the gastrointestinal tract using
optical coherence tomography: preliminary results.
AB - BACKGROUND: Optical coherence tomography (OCT) is a novel technique for
noninvasive cross-sectional imaging with high spatial resolution (10 to 20
microm). OCT is similar to B-mode ultrasound except that it uses infrared light
rather than ultrasound. We studied OCT imaging of the gastrointestinal (GI) tract
in vitro to analyze the potential of this technique for endoscopic applications.
METHODS: Human gastrointestinal tissues harvested from surgical resection and
autopsy specimens were used. Specimens were imaged within 5 hours of resection or
snap frozen in liquid nitrogen. After imaging, OCT scan locations were carefully
marked using dye microinjections, fixed, and prepared for routine histologic
processing. OCT images were then compared and correlated with the histologic
sections. RESULTS: OCT images demonstrated clear delineation of the mucosa and
submucosa in most specimens. Furthermore, microscopic structures such as crypts,
blood vessels, or esophageal glands in the submucosa and lymphatic nodules were
observed. CONCLUSIONS: The resolution of OCT images of GI wall is sufficient to
delineate the microscopic structure of the mucosa and submucosa. Potentially, OCT
would allow in vivo imaging at endoscopy of the microstructure of the mucosa and
submucosa. This would be particularly useful in the detection and staging of
small lesions such as early stage cancers.
PMID- 9647379
TI - Farewell to bacteremia caused by endoscopic injection--effectiveness of a new
injection catheter with a covered tip.
AB - BACKGROUND: Endoscopic injection has recently been reported as effective for
several treatments. Because the common channel (suction and biopsy) is usually
contaminated with aspirated gastrointestinal juice containing bacteria, often the
tip of the injector needle is also. We report a new catheter needle with a
covered tip designed to prevent bacteremia from endoscopic injection. METHODS:
The new covered needle catheter (Clisco needle) has a 23-gauge retractable needle
with a 3 mm extrusion in one lumen. Its distal tip is covered with rubber,
blocking infiltration of contaminated gut juice. Ten of these catheters and 10
other disposable needles were inserted through the colonoscope's biopsy channel
for 10 patients. Needle tips were cut off after extrusion, and bacteria cultured
were counted by standard plate count method. RESULTS: All cultures from ordinary
needles grew Escherichia coli, whereas only 3 new needles grew E. coli. Average
counts of bacteria cultured from these 3 catheters and 10 disposable needles were
1-250 and 90-6.1 x 10(6), respectively. The difference was highly significant (p
< 0.0001). CONCLUSIONS: This new covered needle catheter reduces contaminating
bacteria in patients who require endoscopic injection and may prevent bacteremia
without antibiotic prophylaxis.
PMID- 9647380
TI - Alendronate-associated esophagitis: endoscopic and pathologic features.
PMID- 9647381
TI - Esophageal granular cell tumor treated by endoscopic mucosal resection using a
ligating device.
PMID- 9647382
TI - Airway complications of esophageal self-expandable metallic stent.
PMID- 9647383
TI - Spontaneous communication of a liver cyst with the bile ducts diagnosed by ERCP.
PMID- 9647384
TI - A case of pyogenic granuloma in the duodenum: successful treatment by endoscopic
snare polypectomy.
PMID- 9647385
TI - Pneumoperitoneum complicating ERCP performed immediately after EUS-guided fine
needle aspiration.
PMID- 9647386
TI - Biliary stent migration with colonic diverticular perforation.
PMID- 9647387
TI - Pancreatic acinar metaplasia in an inlet patch.
PMID- 9647388
TI - Drug-induced esophageal damage: diseases of medical progress.
PMID- 9647389
TI - The American Society for Gastrointestinal Endoscopy at the turn of the century
and beyond.
PMID- 9647390
TI - Emergency endoscopy in upper gastrointestinal bleeding at a second level unit:
clinical results and quality assurance (QA), three year experience.
PMID- 9647391
TI - Increased serum trypsinogen 2 and trypsin 2-1 antitrypsin complex values identify
endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis with
high accuracy.
PMID- 9647392
TI - Assessment of residual gastric volume and thirst in patients who drink before
gastroscopy.
PMID- 9647393
TI - Endoscopic education in the Scandinavian countries: current status and a call for
standards.
PMID- 9647394
TI - Gastrointestinal endoscopy--a Canadian perspective.
PMID- 9647395
TI - Comment--endoscopic quality and control.
PMID- 9647396
TI - Sigmoido-anal intussusception presenting as rectal prolapse: role of endoscopic
diagnosis.
PMID- 9647397
TI - Role of percutaneous transhepatic cholangioscopy in biliary papillomatosis: can
it change treatment modality?
PMID- 9647398
TI - Post-cholecystectomy bile leaks and their management.
PMID- 9647399
TI - "Unexpected" gastric ecchymosis.
PMID- 9647400
TI - Technology Assessment Status Evaluation: botulinum toxin therapy in
gastrointestinal endoscopy. November, 1996. ASGE. American Society for
Gastrointestinal Endoscopy.
PMID- 9647401
TI - Technology Assessment Status Evaluation--update: endoscopic band ligation.
November, 1996. ASGE. American Society for Gastrointestinal Endoscopy.
PMID- 9647402
TI - Technology Assessment Status Evaluation: tissue sampling during endosonography.
February 1997. ASGE. American Society for Gastrointestinal Endoscopy.
PMID- 9647403
TI - Technology Assessment Status Evaluation: guidewires in gastrointestinal
endoscopy. February, 1997. ASGE. American Society for Gastrointestinal Endoscopy.
PMID- 9647404
TI - Technology Assessment Status Evaluation update: transvenous intrahepatic
portosystemic shunt (TIPS). April, 1997. ASGE. American Society for
Gastrointestinal Endoscopy.
PMID- 9647405
TI - Technology Assessment Status Evaluation: stents for gastrointestinal strictures.
May, 1997. ASGE. American Society for Gastrointestinal Endoscopy.
PMID- 9647406
TI - The new heparins.
PMID- 9647407
TI - Novel anticoagulants based on direct inhibition of thrombin and factor Xa.
PMID- 9647408
TI - Novel anticoagulants based on inhibition of the factor VIIa/tissue factor
pathway.
PMID- 9647409
TI - Novel antithrombotics based on modulation of the protein C pathway.
PMID- 9647410
TI - Novel approaches to thrombolysis based on modulation of endogenous fibrinolysis.
PMID- 9647411
TI - Coronary vasoreactivity to ergonovine after angioplasty: difference between the
infarct-related coronary artery and the noninfarct-related coronary artery.
AB - BACKGROUND: The vasoreactivity after direct percutaneous transluminal coronary
angioplasty (PTCA) in patients with previous myocardial infarction remains
unknown. We examined the constrictor response to ergonovine of the infarct
related coronary artery in comparison with that of noninfarct-related coronary
artery after angioplasty. METHODS: Ergonovine was administered intravenously to
17 patients with previous myocardial infarction (group I) and to 21 patients with
stable angina (group II) 1 year after PTCA. The effects of ergonovine on lumen
diameter were analysed quantitatively at the PTCA segment, nonPTCA segment
(proximal to the PTCA segment), and nonPTCA artery. RESULTS: The ergonovine
induced decrease in minimal lumen diameter at the PTCA segment was significant in
group I (decrease from 2.12 +/- 0.56 to 1.39 +/- 0.74 mm, P < 0.01), but not in
group II (decrease from 1.60 +/- 0.35 to 1.43 +/- 0.33 mm, NS). Patients in group
I showed a constrictor response at the nonPTCA artery (decrease in diameter from
2.54 +/- 0.90 to 1.94 +/- 0.77 mm, P < 0.01), and a tendency to constrict at the
nonPTCA segment (2.56 +/- 0.67 to 2.11 +/- 0.66 mm, P = 0.06), whereas those in
group II showed no significant constrictor response to ergonovine at any of the
three segments examined. The changes in diameter at the three segments in
patients in group I were significantly greater than those in group II (all P <
0.01). Subtotal coronary spasm at the PTCA segment was provoked only in three
patients in group I (18%). CONCLUSIONS: The constrictor response to ergonovine of
the infarct-related coronary artery was enhanced compared with that of the
noninfarct-related coronary artery. This difference in coronary vasoreactivity at
the angioplasty segment may be due to previous hypersensitivity of the smooth
muscle.
PMID- 9647412
TI - Whole blood viscosity and haematocrit are associated with internal carotid
atherosclerosis in men.
AB - BACKGROUND: Alterations in blood viscosity and haematocrit have been described in
patients with coronary and cerebrovascular diseases. The results have not been
conclusive, as modifications of these parameters are often associated with the
presence of coronary heart disease (CHD) risk factors. The aim of this study was
to verify whether blood viscosity and haematocrit are increased in patients with
carotid atherosclerosis, independently of the presence of CHD risk factors.
METHODS: Male patients with internal carotid atherosclerosis (ICA+, n = 28) were
selected from participants in a cardiovascular disease prevention campaign.
Controls (ICA-, n = 28), also participating in the prevention campaign, were
matched for age and all the classical CHD risk factors. Plasma lipids, glucose
and fibrinogen were determined by routine methods. Cigarette smoking and current
drug therapy was established by questionnaire. Whole blood viscosity was measured
at shear rates of 450 and 225/s, using a cone-plate viscometer. Echo-Doppler of
carotid arteries was performed with an ATL Ultramark 9 HDI using a 5-10 MHz
multifrequency probe. RESULTS: Blood pressure, plasma lipids, glucose, body mass
index, fibrinogen and plasma viscosity were similar in the two groups. ICA+
patients, compared with the ICA- group, had significantly greater values of blood
viscosity (4.52 +/- 0.37 cP compared with 4.18 +/- 0.45 cP, P < 0.005
respectively; shear rate 450/s) and haematocrit (48.57 +/- 3.19% compared with
45.57 +/- 4.81%, P < 0.008 respectively). CONCLUSIONS: Our findings demonstrate
that blood viscosity and haematocrit are increased in men with internal carotid
atherosclerosis, independently of the presence of risk factors for
atherosclerosis.
PMID- 9647413
TI - Failure to confirm ferritin and caeruloplasmin as risk factors for the
angiographic extent of coronary arteriosclerosis.
AB - BACKGROUND: It has been suggested that iron overload, as assessed by increased
serum ferritin concentration, may be a risk factor for coronary artery disease
(CAD). Recent studies have reported conflicting data on the role of ferritin and
other parameters of oxidative metabolism in CAD. OBJECTIVE: The aim of this study
was to assess the relation between the extent of CAD and parameters of oxidation.
METHODS: We studied 275 patients (208 men aged 55.1 +/- 9.6 years and 67 women
aged 54.6 +/- 10.0 years) who underwent coronary angiography or percutaneous
transluminal coronary angioplasty for the first time. The parameters assessed
were: iron, ferritin, transferrin, copper, caeruloplasmin and lipid. Cinefilms
were assessed by the use of three scores: (1) Vessel score: 0-3 points; 1 point
for each of the three main coronary arteries with a stenosis >70%. (2) Stenosis
score: 0-32 points; the coronary artery tree was divided into eight segments that
were scored 1-4 points per segment with respect to the maximal degree of
stenosis. (3) Extent score: 0-100 points; extent of diffuse coronary lesions in
each segment in relation to the length of the vessel. Multiple regression
analyses were used to evaluate the results. RESULTS: Total cholesterol and low
density lipoprotein cholesterol (P < 0.001) in women, low-density lipoprotein
cholesterol (P < 0.05) in men, and patient age showed a significant correlation
with all three scores, but none of the parameters of oxidative metabolism (iron,
transferrin, ferritin, copper, caeruloplasmin) correlated significantly with any
of the three scores. CONCLUSION: This study demonstrated a correlation between
lipoproteins and the angiographic extent of CAD, but did not confirm a role for
serum ferritin and other oxidative parameters as risk factors for the extent of
CAD.
PMID- 9647414
TI - Relation between successful late coronary angioplasty of an occluded, infarction
related artery and lower prevalence of ventricular late potentials.
AB - BACKGROUND: The effect of mechanical reperfusion of the infarction-related artery
on ventricular late potentials (VLP) continues to be debated. OBJECTIVE: To
assess the influence of successful late coronary angioplasty on the prevalence of
VLP after acute myocardial infarction (AMI). METHODS: We studied 113 consecutive
patients (97 men, 16 women, mean age 57 +/- 10.8 years) in whom the infarction
related artery was occluded (thrombolysis in myocardial infarction score 0 or 1)
at the time of the initial coronary arteriography 10.9 +/- 6.4 days after a first
AMI. Successful late angioplasty of the infarcted artery was performed in 55
patients a mean of 11.5 +/- 7.2 days after AMI. The remaining 58 patients
received a conservative treatment. Signal-averaged electrocardiograms (SAECGs)
were recorded 25 +/- 10.2 days after AMI. Multivariate analysis was undertaken to
assess the influence of late coronary angioplasty with respect to age, sex,
infarction site, angiographic ejection fraction, extent of diseased coronary
arteries, thrombolysis and time of recording the SAECG. RESULTS: The overall
prevalence of VLP was 27%. It was greater in patients without than in those with
angioplasty (40% compared with 15%, P = 0.017). Multivariate analysis
demonstrated that successful angioplasty (odds ratio 3.2; P = 0.019) and ejection
fraction >0.4 (odds ratio 5.1; P = 0.0051) were the strongest independent
predictors of an absence of VLP. 'Non-inferior' myocardial infarction was also
correlated with the absence of VLP (odds ratio 2.6), but with borderline
significance (P = 0.053). CONCLUSION: When performed in an occluded, infarction
related artery, successful late coronary angioplasty contributes to a significant
decrease in the prevalence of VLP.
PMID- 9647415
TI - Novel technetium-99m-labeled platelet GPIIb/IIIa receptor antagonists as
potential imaging agents for venous and arterial thrombosis.
AB - OBJECTIVES: Either venous or arterial thrombosis is a potentially life
threatening event and existing diagnostic modalities are inadequate to diagnose
and to determine the morphology of the evolving thrombus. Thus development of a
noninvasive imaging agent that can detect clot location remains a critical and
unmet need in nuclear diagnostic medicine. The present study was undertaken to
determine the potential of platelet GPIIb/IIIa receptors compared with direct
thrombin inhibitors, in the detection of venous and arterial clots. METHODS:
Initially, the validity of exploiting the degree and extent of specific uptake
and retention of a potent GPIIb/IIIa receptor antagonist in venous and in
arterial thrombus was confirmed in vitro in artificially created arterial- or
venous-type clots, using the radiolabeled antagonist, 3H-DMP728. This was
followed by comparing the in-vivo clot/blood distribution of various technetium
99m (99mTc)-labeled, DMP728-derived, GPIIb/IIIa receptor antagonists and of
thrombin inhibitors, over time, in mixed arterial/venous or venous clots in
arteriovenous shunt and in venous clot models in dogs. In addition, we performed
noninvasive single-photon emission tomographic imaging of the venous clot in a
deep vein thrombosis model in dogs. RESULTS: Our data confirmed that potency for
the platelet GPIIb/IIIa receptors was maintained after radiolabeling of the
parent active GPIIb/IIIa receptor antagonists. DMP728 demonstrated a relatively
greater affinity for activated than for unactivated human platelets, which might
be essential for attaining an optimal thrombus/blood (target/background)
distribution ratio and the optimal detection of small clots (i.e. greater
sensitivity). CONCLUSIONS: These data suggest a potential utility of 99mTc
GPIIb/IIIa receptor antagonists, but not of direct thrombin inhibitors, in the
diagnosis of venous clots in deep vein thrombosis, pulmonary embolism and
arterial thromboembolic disorders including stroke and coronary and peripheral
artery thrombotic disorders.
PMID- 9647417
TI - Bibliography of current world literature.
PMID- 9647418
TI - Couples relapse prevention sessions after behavioral marital therapy for male
alcoholics: outcomes during the three years after starting treatment.
AB - OBJECTIVE: This article provides a complete report of outcome data from a study
of behavioral marital therapy (BMT) with and without additional couples relapse
prevention (RP) sessions. (See J. Stud. Alcohol 54: 652-666, 1993, for an earlier
partial report.) METHOD: Fifty-nine couples with an alcoholic husband, after
receiving weekly BMT couples sessions for 5-6 months, were assigned randomly to
get or not get 15 additional couples relapse prevention (RP) sessions over the
next 12 months. Outcome measures were collected before and after BMT and at
quarterly intervals for the 30 months after BMT. RESULTS: BMT-plus-RP produced
more days abstinent and greater use of the Antabuse Contract than BMT-only; and
these superior drinking outcomes for BMT-plus-RP lasted through 18-month follow
up (i.e., 6 months after the end of RP). BMT-plus-RP had better wives' marital
adjustment than BMT-only throughout the 30 months of follow-up, with the
superiority of BMT-plus-RP over BMT-only being greatest for wives with poorer
pretreatment marital adjustment during the later months of follow-up. BMT-plus-RP
also maintained their improved marriages longer (through 24-month follow-up) than
BMT-only (through 12-month follow-up). Irrespective of treatment condition, more
use of BMT-targeted marital behaviors (e.g., shared recreational activities,
constructive communication) was associated with better marital and drinking
outcomes throughout the 30-month follow-up period whereas more use of the
Antabuse contract was associated with better marital and drinking outcomes
through 12-month follow-up. Alcoholics with more severe marital problems had more
abstinent days and maintained relatively stable levels of abstinence if they
received BMT-plus-RP, while their counterparts who received BMT-only had fewer
abstinent days and showed a steep decline in abstinent days during the 30 months
of follow-up. Furthermore, alcoholics with more severe alcohol problems used the
Antabuse contract more and showed a less steep decline in use of the Antabuse
contract in the 30 months of follow-up if they received BMT-plus-RP than if they
received BMT-only. CONCLUSIONS: For the entire sample, BMT-plus-RP produced
better marital outcomes throughout the 30 months of follow-up and better drinking
outcomes during and for the 6 months following RP sessions, relative to BMT-only
outcomes. For alcoholics with more severe marital and drinking problems, BMT-plus
RP produced better drinking outcomes than BMT-only throughout the 30-month follow
up period.
PMID- 9647416
TI - Structural, biochemical and functional effects of distending pressure in the
human saphenous vein: implications for bypass grafting.
AB - BACKGROUND: Distension of the saphenous vein before and after coronary artery
bypass grafting results in damage to mechanisms that regulate vascular tone. We
have investigated the relationship between the magnitude of distending pressure
and the degree of structural, biochemical and functional damage to the vessel
wall. METHODS: Vessel segments that had been distended to either 100 or 300 mmHg
were set up in isolated organ baths and the function of the smooth muscle and
endothelial cells examined. All segments examined were then fixed for assessment
of structural damage by scanning electron microscopy and for immunocytochemical
localisation of endothelial nitric oxide synthase. RESULTS: Segments of saphenous
vein distended to 100 mmHg retained their responsiveness to KCl (90 mmol/l) and
phenylephrine (10(-6) mol/l), but those pressurised to 300 mmHg had significantly
reduced responses to both agents. There was also a significant reduction in
response to the endothelium-dependent dilators, acetylcholine (10(-10)-10(-6)
mol/l) and bradykinin (10(-10)-10(-6) mol/l) in those segments distended to 300
mmHg. Quantitative studies of structural endothelial damage showed a significant
loss of endothelium at 300 mmHg distension pressure. Remaining endothelial cells
retained strong positive staining for endothelial nitric oxide synthase. By
electron microscopic examination, those vessels distended to 100 mmHg showed
lifting and rounding of individual cells, whereas segments distended to 300 mmHg
revealed major areas of denuded endothelium. CONCLUSIONS: Distension of saphenous
veins to pressures equivalent to those in the systemic circulation result in
structural and biochemical changes in the endothelium that are not paralleled by
immediate functional vasomotor changes.
PMID- 9647419
TI - Evaluating substance abuse treatment process models: I. Changes on proximal
outcome variables during 12-step and cognitive-behavioral treatment.
AB - OBJECTIVE: This article provides data on the early linkages in the treatment
process chains that are thought to underlie two prevalent approaches to substance
abuse treatment-traditional 12-step treatment and cognitive-behavioral treatment.
The focus is on the during-treatment changes on "proximal outcomes" that,
according to the treatment theory underlying each modality, patients are supposed
to undergo or achieve in order to experience a positive "ultimate outcome."
METHOD: In all, 3,228 men receiving treatment in 15 Department of Veterans
Affairs substance abuse treatment programs were assessed at treatment entry and
at or near discharge from inpatient programs that had desired lengths of stay of
21-28 days. RESULTS: Between intake and discharge, patients in 12-step programs
improved more than did C-B patients on proximal outcome variables assumed to be
specific to 12-step treatment (e.g., attending 12-step meetings, taking steps),
whereas patients in cognitive-behavioral programs made no greater change (and in
a few cases, less change) than did 12-step patients on proximal outcome variables
assumed to underlie cognitive-behavioral treatment (e.g., self-efficacy, coping
skills). CONCLUSIONS: These findings suggest that the proximal outcomes thought
to be specific to cognitive-behavioral treatment are actually general proximal
outcomes of both 12-step and cognitive-behavioral treatment.
PMID- 9647420
TI - Reflecting adult drinking culture: prevalence of alcohol use and drinking
situations among Japanese junior high school students in Japan.
AB - OBJECTIVE: To estimate the prevalence of Japanese adolescents' alcohol use in
Japan and the situations surrounding their drinking. METHOD: A general population
self-administered questionnaire survey was conducted with a sample of 5,240
Japanese junior high school students obtained from 12 representative schools of
the Chiba Prefecture in Japan. RESULTS: Almost 80% of the boys and 75% of the
girls reported having consumed an alcoholic beverage on at least one occasion.
Consumption occurred most frequently on a ceremonial occasion (52.4%), followed
by drinking with family (39.0%), with peers (20.6%), after a bath (9.7%) and at
ritual parties among friends (9.3%). In this sample, a greater percentage of
students in a higher grade reported a drinking occasion after a bath, at parties
among friends, or with peers. However, this trend was not observed for drinking
on ceremonial occasions or with family in the evening. A gender difference was
observed for the prevalence of drinking after a bath. A majority of students
agreed with the statement that minors' use of alcohol was "acceptable depending
on the situation." This was in sharp contrast with their perception of cigarette
smoking and solvent use (16.3% and 3.8%, respectively, endorsing the same
statement). CONCLUSIONS: By sometime in their first year of junior high school
(when most students are age 12 years), more than 75% of Japanese adolescents have
tried alcohol. Prevalence rates and trends across grades are different depending
on the occasions of drinking. The findings on situational drinking among
adolescents of this age group appear to reflect that assimilation into Japanese
drinking culture takes place early on in family or traditional settings.
PMID- 9647421
TI - Paternal alcoholism, paternal absence and the development of problem behaviors in
boys from age six to twelve years.
AB - OBJECTIVE: The purpose of this study was to examine the association between
paternal alcoholism, paternal absence, and the development and stability of
behavioral problems in boys, from kindergarten to the end of elementary school.
METHOD: A sample of 642 boys originating from low socioeconomic status (SES)
families was used. Paternal alcoholism was established using the Short Michigan
Alcohol Screening Test. Behavioral problems (opposition, hyperactivity,
inattention, physical aggression and anxiety) were assessed by teachers' reports
when the boys were 6 and 12 years old. Four groups of boys were created on the
basis of paternal alcoholism (nonalcoholic, alcoholic) and family structure
(intact families, nonintact/father-absent families). RESULTS: Consistent with
personality theories of alcoholism, results showed that a propensity for physical
aggression and low anxiety best distinguished sons of male alcoholics (SOMAs)
from non-SOMAs at both ages (6 and 12 years), even when SES was controlled. In
addition, SOMAs were more oppositional and hyperactive than non-SOMAs at both
ages. No significant effects were observed for family structure or age, or an
interaction between these factors and paternal alcoholism in the multivariate
analysis. CONCLUSIONS: The results suggest that problem behaviors in SOMAs begin
early and persist over time, and that paternal alcoholism and family structure
are not associated with changes in boys' behaviors between kindergarten and the
end of elementary school in this population, at least in the sample used.
PMID- 9647422
TI - Latent variable modeling of longitudinal and multilevel alcohol use data.
AB - OBJECTIVE: This article demonstrates use of a latent variable model for
longitudinal data which encompasses nested structures. Using Multilevel Latent
Growth Modeling (LGM), levels of alcohol use and development of alcohol use over
4 years were examined among individuals (adolescents and parents) nested within
families. METHOD: An LGM model was tested for alcohol use with a sample of 435
families (435 target adolescents, 203 sibling and 566 parents [168 fathers and
398 mothers]). Adolescents (targets and siblings) comprised 312 boys and 326
girls, with a mean (+/-SD) age at Time 1 (T1) of 13.69 +/- 1.95 years. It was
hypothesized that there would be homogeneity in level and development of alcohol
use among family members and heterogeneity in alcohol use and development across
families. The effects of family status (single-parent, two-parent intact and
stepparent families) and socioeconomic status (SES) on family levels of alcohol
use were also examined. RESULTS: Results suggested that stepparent families, and
less educated and more economically disadvantaged families, had higher family
levels of alcohol use and developed in their use of alcohol at a faster rate.
CONCLUSIONS: Findings suggest that the alcohol use of individuals in the same
family is more alike than that of individuals from different families and that
family alcohol use may be influenced by family-level variables such as family
status or SES. Methods such as those presented, which incorporate family-level
clustering, are likely to provide additional information regarding the etiology
of alcohol use and risk factors for alcohol use within and across families.
PMID- 9647423
TI - Alcohol outcome expectancies, attitudes toward drinking and the theory of planned
behavior.
AB - OBJECTIVE: The present study investigated whether alcohol outcome expectancies
are empirically distinguishable from attitudes toward drinking. Specifically, the
contribution of expectancies and attitudes to the Theory of Planned Behavior was
assessed. METHOD: Undergraduates (N = 316; 170 male), of legal drinking age, who
drank at least once a month participated. Intentions to drink "too much" and self
report excessive consumption episodes served as criterion measures, and
attitudes, subjective norm, perceived behavioral control and alcohol outcome
expectancies were employed as predictor variables. Stepwise regression analyses
were performed separately for men and women. RESULTS: The Theory of Planned
Behavior appeared to be a valid framework for predicting excessive alcohol
consumption among undergraduates. The predictive power of the model, however, was
enhanced through the inclusion of gender-specific alcohol outcome expectancies.
Specifically, in addition to attitudes and perceived behavioral control, women's
expectancies for sociability enhanced the prediction of intentions to drink "too
much." Expectancies for sexual functioning (male) and assertiveness (female)
improved the prediction of excessive consumption, over and above intentions and
perceived behavioral control. CONCLUSIONS: Alcohol outcome expectancies, unlike
attitudes, are proximal predictors of excessive alcohol consumption among
undergraduates.
PMID- 9647424
TI - Differences in performance of screening instruments for problem drinking among
blacks, whites and Hispanics in an emergency room population.
AB - OBJECTIVE: The purpose of this study was to compare the performance of a number
of standard screening instruments for alcohol dependence and harmful
drinking/abuse by ethnicity (black, Hispanic and white) and by ethnicity and
gender in an emergency room setting. METHOD: A probability sample of patients (N
= 1,429) was breath analyzed and interviewed at the Santa Clara Valley Medical
Center in San Jose, California. Sensitivity and specificity were analyzed among
current drinkers (n = 857) for the CAGE, Brief MAST, AUDIT, TWEAK, RAPS and other
items against combined ICD- 10 or DSM-IV criteria for alcohol dependence and
separately for alcohol dependence or harmful drinking or abuse. RESULTS:
Screening measures were not found to perform equally well by ethnicity or gender,
with lower sensitivity found for women compared to men. Consistency in
sensitivity of measures was found to vary considerably across ethnic and gender
groups, with some measures (most notably the RAPS and the AUDIT) showing
consistently high sensitivity across subgroups. None of the instruments performed
nearly as well for identifying alcohol dependence or harmful drinking or abuse
combined as for alcohol dependence alone. CONCLUSIONS: Analyses suggest that,
while the RAPS may hold promise for identifying problem drinkers across ethnic
and gender subgroups, it and other screening instruments currently in use require
additional evaluation in a variety of settings to determine their usefulness for
identifying those who could benefit from a brief intervention or referral for
problem drinking.
PMID- 9647425
TI - Psychometric evaluation of the Customary Drinking and Drug Use Record (CDDR): a
measure of adolescent alcohol and drug involvement.
AB - OBJECTIVE: The present study was undertaken to assess the psychometric
characteristics of the Customary Drinking and Drug Use Record (CDDR), an
interviewer-administered questionnaire. The CDDR provides current (past 3 months)
and lifetime measures of four alcohol- and other drug-related domains: level of
involvement, withdrawal characteristics, psychological/behavioral dependence
symptoms, and negative consequences. The present report describes the evaluation
of the psychometric properties of the instrument with youth between the ages of
13 and 22 years who had markedly variable histories of involvement with alcohol
and other psychoactive substances. METHOD: The sample assessed was composed of
166 adolescents recruited from two inpatient substance abuse treatment programs
and 115 adolescents recruited from the community. Of the 281 subjects, 150 were
male. Follow-up interviews with each adolescent and a resource person were
conducted 6, 12, 24 and 48 months after the initial assessment. RESULTS:
Reliability of the CDDR was assessed by examination of internal consistency, test
retest reliability and interrater reliability. Convergent, discriminant and
construct validity were evaluated for each of the CDDR domains, and gender and
ethnic differences on substance involvement were examined. The CDDR was found to
be internally consistent and reliable over time and across interviewers for each
major domain assessed. The findings supported the validity of the four domains of
alcohol and other drug involvement assessed on the CDDR. CONCLUSIONS: The present
results demonstrated convergent validity of the CDDR, ability to differentiate
abusing from nonabusing youth and strong diagnostic specificity when compared to
other standard instruments. The solid psychometric characteristics of the CDDR
support its use for both research and clinical purposes.
PMID- 9647426
TI - Screening college students for alcohol problems: psychometric assessment of the
SASSI-2. Substance Abuse Subtle Screening Inventory.
AB - OBJECTIVE: This study examined the psychometric properties of the Substance Abuse
Subtle Screening Inventory (SASSI-2) with college students. METHOD: The first
part of the study examined the test-retest reliability of the SASSI-2 at 2-week
(n = 55) and 4-week (n = 47) intervals with students recruited from introductory
psychology courses. The second part used a new sample of 164 college students to
assess the internal consistency of the SASSI-2 subscales, the relationship of the
SASSI-2 with other common alcohol screening instruments, and its reactivity to
response biases. Participants completed the SASSI-2 under standard instructions,
or instructions to minimize any alcohol problems they might have (fake good), or
to exaggerate any alcohol problems they might have (fake bad). They then
completed the CAGE, MAC and MAST under those measures' standard instructions.
RESULTS: The 2-week and 4-week test-retest reliability of the SASSI-2 subscales
was moderate to high, but the test-retest reliability for overall classification
as "chemically dependent" or "non-chemically dependent" was moderate at 2 weeks
and relatively poor at 4 weeks. Internal consistencies for the SASSI-2 subscales
ranged from poor to strong (Cronbach alphas ranging from .11 to .93), and the
SASSI-2 drinker classification status correlated moderately with drinker
classifications based on the CAGE, MAC and MAST. There was no difference in the
proportion of participants classified as "chemically dependent" on the SASSI-2
when instructed to "fake good" and under standard instructions, but college
students scored as "chemically dependent" more frequently when instructed to
"fake bad." CONCLUSIONS: When the SASSI-2 is used with college students, its
reliability and validity are comparable to other instruments that currently exist
in the public domain. The vulnerability of the SASSI-2 to intentional faking
warrants further investigation.
PMID- 9647427
TI - Levels and patterns of alcohol consumption using timeline follow-back, daily
diaries and real-time "electronic interviews".
AB - OBJECTIVE: This study was designed to compare the Timeline Follow-Back (TLFB) to
daily and real-time assessments of drinking. Our purpose was to evaluate overall
correspondence and day-to-day agreement between these two methods among both
problem and moderate drinkers. METHOD: In Study 1, problem drinkers (n = 20)
reported their alcohol consumption daily during 28 days of brief treatment. In
Study 2, moderate drinkers (n = 48), recruited from the community, used a palm
top computer to record their drinking for 30 days. In both studies participants
completed the TLFB covering the recording period. RESULTS: Participants in Study
1 reported fewer drinking days, fewer drinks per drinking day and fewer total
drinks per day on the TLFB, and those in Study 2 reported fewer drinks per
drinking day, fewer ounces per drinking day, fewer total drinks per day and fewer
total ounces per day. The magnitude of the difference, however, was modest. There
was considerable between-person variation in day-to-day correspondence of TLFB
and the daily and real-time reports. Neither person characteristics (gender,
education and income) nor the distributional characteristics of drinking
(including average consumption, variation) predicted concordance between TLFB and
real-time reports. CONCLUSIONS: The Timeline Follow-Back method captured overall
levels of drinking quite well compared to a 28-day daily diary and a 30-day
electronic interview. Vast individual differences in day-to-day correspondence
suggest that the TLFB may be less useful for detecting patterns of consumption.
PMID- 9647428
TI - Time series analysis of alcohol consumption and suicide mortality in the United
States, 1934-1987.
AB - OBJECTIVE: The objective is to analyze time series data on per capita alcohol
consumption and suicide mortality between 1934 and 1987. Specifically, the aim is
to test the hypothesis that increases in per capita consumption are associated
with increases in suicide mortality overall and in gender and age subgroups. This
study also examines whether the effect of per capita consumption on subsequent
rates of suicide is influenced by other aggregate factors, particularly
unemployment rates, per capita income and divorce rates. METHOD: This analysis
examines the temporal structure of suicide mortality, alcohol consumption and
covariate time series data in the United States, 1934-1987, using the Box-Jenkins
method. RESULTS: Bivariate associations between alcohol consumption and suicide
rates were not significant. However, when unemployment was included in the model,
increases in per capita alcohol consumption were significantly related to
increases in suicide overall, for men and women, and for the young (under age 40)
and middle-aged (40 to 59 years), but not for those over age 60. CONCLUSIONS: The
use in modeling of other known covariates of suicide rates, particularly
unemployment, affects the magnitude of the relationship between alcohol
consumption and suicide. Consistent with other studies, unemployment was
significantly related to suicide and was shown to confound the relationship
between alcohol and suicide. The effects of changes in alcohol consumption on
changes in suicide rates differ by gender and age group, which demonstrates that
focusing on the total population alone can mask divergent effects that can cancel
each other out when subgroups are combined.
PMID- 9647429
TI - Costs and benefits of a community sobriety checkpoint program.
AB - OBJECTIVE: Alcohol-involved crashes cost society more than $100 billion a year.
Sobriety checkpoints are effective in apprehending drunk drivers. This article
compares the costs and the estimated monetary benefits from a hypothetical
community sobriety checkpoint program. METHOD: The analysis is constructed around
a hypothetical community with 100,000 licensed drivers. A literature review
suggests that a generously funded intensive checkpoint program (156 checkpoints
per year) can be expected to reduce alcohol-attributable crashes by about 15%.
The benefits (cost savings) of the checkpoint program are calculated using 1993
alcohol-involved crash incidence from the National Highway Traffic Safety
Administration. Costs per alcohol-involved crash and the percentage of alcohol
involved crashes attributable to alcohol are updated from published studies.
RESULTS: Estimated annual savings to the hypothetical community total $7.9
million. This includes $3.1 million for averted fatalities, $4.5 million for
averted non-fatal injuries, and $0.3 million for averted property damage. Every
$1 spent on a sobriety checkpoint program can be expected to save the community
more than $6, including $1.30 of insurer costs. CONCLUSIONS: An intensive
sobriety checkpoint program can save a community more in automobile crash costs
than the program costs.
PMID- 9647430
TI - The origins and evolution of the disease concept of treatment.
AB - OBJECTIVE: The disease concept of treatment (DCT) has been the dominant treatment
model for alcoholism in the United States for the last 30 years. This article
sheds light on this treatment model by tracing its historical origins and its
evolution in institutions. METHOD: Accounts from the published literature on
Alcoholics Anonymous (AA) and early alcoholism treatment programs were culled for
insights regarding the development of DCT. Early examples of AA facilities, state
mental hospital alcoholism units, detoxification units, and outpatient alcoholism
clinics are described as they evolved. The important role of AA in this process
is detailed. Accounts are given of the interaction between professionals and
alcoholism counselors during the period in which DCT was developed in these
institutions. RESULTS: It was found that all of the current types of alcoholism
treatment programs had their origins in early, informal AA facilities except for
outpatient alcoholism clinics. DCT evolved concurrently in AA facilities, state
mental hospitals and detoxification units. CONCLUSIONS: The historical accounts
summarized here suggest that DCT was primarily a structured and didactic
presentation of AA principles that incorporated some additional treatment
elements, notably, the confrontation group. Thus, it can be argued that most
alcoholism treatment today (i.e., DCT) derives from the original AA model. It is
suggested that studies be undertaken to distinguish the degree to which AA
recovery principles are different from DCT methods by researching the clinical
beliefs and practices of alcoholism counselors and comparing them with those of
AA members.
PMID- 9647431
TI - Overdiagnosis of major psychiatric disorders in individuals with substance use
disorders and personality disorders: the downside of the Woodruff principle.
PMID- 9647432
TI - One-year chromaffin cell allograft survival in cancer patients with chronic pain:
morphological and functional evidence.
AB - The control of chronic pain through transplantation of chromaffin cells has been
reported over the past few years. Analgesic effects are principally due to the
production of opioid peptides and catecholamines by chromaffin cells. Clinical
trials have been reported with allografts consisting of whole-tissue fragments
implanted into the subarachnoid space of the lumbar spinal cord (14,19,36). In
the present study, allogeneic grafts were successfully used to control chronic
pain in two patients over a period of 1 yr based on patient reported pain scores,
morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at
autopsy located the transplanted tissue fragments in the form of multilobulated
nodules at the level of the spinal axis and cauda equina. Immunocytochemical
microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and
enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH). The
results suggest that there is a relationship between analgesic effect, Met
enkephalin levels in CSF, and the presence of chromaffin cells surviving in
spinal subarachnoid space.
PMID- 9647433
TI - Cardiomyocyte transplantation in a porcine myocardial infarction model.
AB - Transplantation of cardiomyocytes into the heart is a potential treatment for
replacing damaged cardiac muscle. To investigate the feasibility and efficiency
of this technique, either a cardiac-derived cell line (HL-1 cells), or normal
fetal or neonatal pig cardiomyocytes were grafted into a porcine model of
myocardial infarction. The myocardial infarction was created by the placement of
an embolization coil in the distal portion of the left anterior descending artery
in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three
preparations of cardiomyocytes were grafted, at 1 x 10(6) cells/20 microL into
normal and into the middle of the infarcted myocardium. The hearts were harvested
and processed for histologic examinations 4 to 5 wk after the cell grafts.
Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal
pig cardiomyocytes formed stable grafts within the normal myocardium without any
detrimental effect including arrhythmia. In addition, a marked increase in
angiogenesis was observed both within the grafts and adjacent host myocardium.
Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the
host myocardial cells were coupled with adherens-type junctions and gap
junctions. Histologic examination of graft sites from infarct tissue failed to
show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes.
Cardiomyocyte transplantation may provide the potential means for cell-mediated
gene therapy for introduction of therapeutic molecules into the heart.
PMID- 9647434
TI - Intrasplenic liver parenchymal cells in conjunction with low-dose rapamycin and
cyclosporine induce a unique and specific prolongation of rat cardiac and small
bowel allograft survival.
AB - These experiments investigated the immunosuppressive properties of liver tissue.
Brown Norway (BN; RT1n) rat heart allografts survived in untreated control Wistar
Furth (WFu; RTl(u)) rat recipients for 6.2 +/- 1.5 days, while allografts in
animals that received rapamycin (RAPA) 0.0075 mg/kg/day and cyclosporine (CsA)
0.375 mg/kg/day delivered for 14 days by continuous intravenous infusion (civi)
using osmotic pumps in conjunction with intrasplenic (i.s.) saline survived to
18.4 +/- 1.3 days. i.s. addition of 3 M-KCl extracted BN hepatic antigen or
unpurified BN hepatocytes (liver parenchymal cells-5 x 10(7)/kg), which exhibited
a 4.8% class II antigen expression, and which alone failed to prolong allograft
survival (MST = 6.0 +/- 1.4 days), increased heart allograft survival to 25.3 +/-
2.3 and 27.2 +/- 1.9 days, respectively (p < 0.01). Hepatocyte purification using
Dynabeads and Percoll reduced class II expression to 0.9% and increased allograft
survival to 32.8 +/- 1.6 days (p < 0.01). In contrast, the effect of 5 x 10(8)/kg
BN erythrocytes, exhibiting only 0.1% class II expression, was much less (23.8 +/
1.9 days). Administration i.s. of BN splenocytes or nonparenchymal liver cells,
demonstrated by flow cytometry to exhibit a 47.3 or 55.1% expression of class II
antigen, respectively, failed to induce any significant increase in allograft
survival (18.4 +/- 4.6 and 19.4 +/- 0.5 days, respectively). Survival of BN rat
small bowel allografts was increased in Lewis (LEW; RTl1) rat recipients treated
with RAPA, CsA, and unfractionated BN hepatocytes from 10.2 +/- 1.9 to 21.2 +/-
1.5 days. Pretreatment with i.s. BN hepatocytes, 14 days prior to harvesting,
reduced WFu lymphocyte responses to allogeneic stimulation with BN or ACI spleen
cells by 75 and 70%, respectively. Addition of 1 x 10(5) unpurified donor
specific BN or third-party Buffalo (BUF; RTl(b)) hepatocytes, but not
supernatant, to the responder wells of MLCs resulted in a 61 and 40% suppression,
respectively, of the WFu lymphocyte response induced by BN allogeneic
stimulation. These findings suggest that while class I MHC expression has a
significant role to play in exerting the immunosuppressive effects of
hepatocytes, other influences more specific to liver may also prevail.
PMID- 9647435
TI - Response of cultured fetal and adult rat hepatocytes to growth factors and
cyclosporine.
AB - Hepatocyte transplantation is a promising alternative to orthotopic liver
transplantation in experimental animal models with genetic disorders of liver
metabolism and liver failure. Fetal hepatocytes have several characteristics that
make them potentially suitable as donor cells. In contrast to adult hepatocytes,
fetal hepatocytes are thought to be highly proliferative, which may facilitate
engraftment, expansion of transplanted cell population, and gene transfer
requiring active DNA synthesis. The present study was undertaken to evaluate the
proliferative capacity of fetal and adult rat hepatocytes under standardized
culture conditions. Fetal (20 days of gestation) and adult hepatocytes were
cultured in serum-free media at low densities and treated with growth factors.
Proliferation was assessed by [3H]-thymidine incorporation and cell cycle
analysis by flow cytometry. In nonstimulated cells, DNA synthesis at 4 h was
about x100 higher and after 10 days in culture x20 higher in fetal compared to
adult hepatocytes. When epidermal growth factor (EGF) was added, maximal DNA
synthesis in fetal hepatocytes was seen at 48 h, whereas in adult hepatocytes at
72 h. For adult hepatocytes, the average increase compared to untreated cells was
x13.8 with EGF, x18.5 with transforming growth factor alpha (TGF-alpha), and x7.6
with hepatocyte growth factor (HGF). For fetal hepatocytes, the increase was
twofold with either EGF, TGF-alpha or HGF. EGF-, TGF-alpha- and HGF-dependent DNA
synthesis was inhibited by transforming growth factor beta-1 (TGF-beta1) in both
fetal and adult hepatocyte cultures; this antiproliferative effect was
significantly stronger in adult hepatocyte cultures. With cyclosporine, EGF-, TGF
alpha- and HGF-dependent DNA synthesis in fetal hepatocyte cultures decreased by
36-46%, whereas in adult hepatocytes by 19-27 %. These results show that in
contrast to adult hepatocytes, fetal hepatocytes have high spontaneous
proliferative activity independently of growth factors and are relatively
resistant to the inhibitory effect of TGF-beta1. It was also found that
cyclosporine suppresses proliferation of cultured fetal hepatocytes.
PMID- 9647436
TI - In vivo identification, survival, and functional efficacy of transplanted
hepatocytes in acute liver failure mice model by FISH using Y-chromosome probe.
AB - Hepatocyte transplantation has excited much interest in lending temporary
metabolic support to a failing liver following acute liver injury. The exact site
from which they act and the clinical, biochemical, and histological changes in
the recipient body following hepatocyte transplantation is yet to be worked out.
The present study is an attempt to delineate location and function of
transplanted hepatocytes and also the overall survival of these cells with a
fluorescent in situ hybridization (FISH) technique using a Y-chromosome-specific
probe in a carbon tetrachloride (CCl4)-induced mice model of fulminant hepatic
failure. Fifty-five syngenic adult Swiss female mice of approximately the same
age and body weight were divided into three groups. Group-1 (n = 15), which
received mineral oil, served as a negative control. Group-II (n = 15) received
CCl4 (3 mL/kg) 40% vol/vol in mineral oil, by gavage served as positive control
for hepatic failure. Group-III (n = 25) received intrasplenic transplantation of
syngenic single cell suspension of hepatocytes in Hanks medium, after 30 h of
CCl4 administration. Male Swiss adult mice (n = 15) served as donors of
hepatocytes. The overall survival of animals in groups I to III was 100, 0, and
70%, respectively, by 2 wk of the study period. Transplanted hepatocytes were
identified by Periodic Acid Schiff (PAS) staining and confirmed with a FISH
technique using the Y-chromosome probe. The majority of exogenously transplanted
hepatocytes were found in the liver and spleen sections even after 1 wk of
hepatocyte transplantation. Transplanted cells were mostly found to be
translocated into the sinusoids of the liver. Transplanted hepatocytes were found
to be beneficial as a temporary liver support in a failing liver, significantly
improving the survival of the animals. In the present study, the FISH technique
was used to unequivocally distinguish the transplanted cells from the host, and
thus describes a model for studying the distribution and survival of the
transplanted cells.
PMID- 9647437
TI - Human serum albumin microspheres approximate initial organ-specific
biodistributions of transplanted hepatocytes and are effective cell surrogates
for safety studies.
AB - Liver repopulation with transplanted hepatocytes will generate novel cell-based
therapies, although translocation of transplanted cells into lungs through
portasystemic shunts has the potential for embolic complications. To facilitate
safety analysis of hepatocyte transplantation, we wished to obtain effective cell
surrogates and analyzed biodistributions of similarly sized 99mTc-labeled human
serum albumin microspheres and rat hepatocytes. Image analysis with dual 99mTc
and 111In labels indicated that cells and microspheres were similarly distributed
in the liver when injected into normal rats via the spleen. Also, their
distributions were similar when injected via a femoral vein or the superior
mesenteric vein with cells and microspheres localizing in lungs or liver,
respectively. Upon intraportal injection in rats with portal hypertension,
microspheres localized in both liver and lungs, consistent with portasystemic
shunting. These data demonstrate that human serum albumin microspheres are
effective cell surrogates for approximating the safety of hepatocyte
transplantation and should be clinically useful.
PMID- 9647438
TI - Islet allograft rejection in rats: a time course study characterizing adhesion
molecule expression, MHC expression, and infiltrate immunophenotypes.
AB - Wistar Furth (RT1u) islets transplanted under the renal capsules of
streptozotocin-diabetic Lewis (RT1l) rats reject after 5-6 days of normoglycemia.
Hand-picked WF islets (1500-2000) were transplanted under the kidney capsules of
diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on
posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls
were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B
cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells,
parenchymal cells, and endothelial cells in five distinct compartments (i.e.,
peritoneal reflection, subcapsular perivascular space, islet grafts, graft-kidney
interface, and kidney) were evaluated for expression of the various markers at
each interval. Significant infiltrates arrived in three distinct waves in both
iso- and allografts. First, macrophages blanketed the peritoneal capsular
reflection and infiltrated by day 2. Second, the first wave of lymphocytes
arrived in the edematous subcapsular soft tissue via capsular vessels by day 2
(allo > iso). Third, the second wave of lymphocytes arrived from the renal
parenchyma to form a dense band at the graft-kidney interface and around grafts
by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with
CD4+ cells being mobilized first and from interstitial vessels throughout the
entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent
to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in
the infiltrates with the most intensely staining cells being intravascular. B
cells composed a very small proportion of infiltrating cells in both allo- and
isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout.
Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial
cells, but neither was found on islet parenchymal cells. In conclusion, this
study shows that islet allograft rejection is more complex than previously
realized.
PMID- 9647439
TI - Tilapia--a source of hypoxia-resistant islet cells for encapsulation.
AB - Encapsulation of pancreatic islets prevents graft revascularization after
transplantation, resulting in graft hypoxia and attrition. Hypoxia-resistant
islets would be ideal for encapsulation. Tilapia, a tropical teleost fish, have
large, anatomically discrete islets that can be easily harvested without
expensive, fickle islet isolation procedures and that provide mammalian-like
glucose tolerance profiles when transplanted into diabetic recipients. Because
tilapia can live in stagnant water, we speculated that tilapia islets might
tolerate lower oxygen tensions than mammalian islets. Tilapia and rat islets (n =
30) were placed in paired 60-mm Petri dishes containing 10 mL of deoxygenated
CMRL-1066 media and cultured together in sealed chambers gassed with 95% N2/5%
CO2. Islet viability was determined by fluorscein diacetate/ethidium bromide
staining at intervals varying from 2.5 h to 7 days; blood gas measurements were
obtained on media samples at the end of selected incubation intervals. Rat islets
underwent near-total necrosis and fragmentation in <24 h; occasional viable
single cells could be identified until about 72 h. On the other hand, the fish
islets showed no loss of viability until about 72 h when some showed mild central
necrosis. Even at 7 days, all fish islets appeared roughly 50% viable. Fish
islets cultured under hypoxic conditions for 72 h (media, pO2 = 27.8 mmHg) and
then transplanted into streptozotocin-diabetic athymic nude mice were viable
(6/6) but showed some diminished function (3/6) over a 25-day follow-up period.
Our results suggest that tilapia islets will survive and function at lower oxygen
tensions than mammalian islets.
PMID- 9647440
TI - Single-cell suspensions of cultured human keratinocytes in fibrin-glue
reconstitute the epidermis.
AB - To overcome common disadvantages of standard cultured epidermal sheet grafts
(CEG) we have developed a new technique of transplanting cultured human
keratinocytes suspended as single cells in a fibrin-glue matrix (Keratinocyte
fibrin-glue suspension-KFGS). In an athymic mouse model with reproducible
standardized full thickness wounds this new technique was compared directly to
CEG. Reepithelialization was similar in both groups, but reconstitution of the
dermo-epidermal junction zone, as shown by electron microscopy and
immunohistochemistry was significantly enhanced by the fibrin-glue suspension
technique. The new KFGS technique is earlier available than sheet grafts, is able
to transfer actively proliferative single keratinocytes, and simplifies the
application.
PMID- 9647441
TI - Perfusion enhances functions of bone marrow stromal cells in three-dimensional
culture.
AB - Perfusion of medium through three-dimensional (3D) collagen sponges enhanced
viability and function of cocultivated marrow stromal and hematopoietic cell
lines. Cells of the murine bone marrow stromal cell line GPIa were cultured in
novel 3D collagen sponges, made from pepsin-digested bovine skin. Static cultures
of sponges were maintained in dishes with media changes every other day. Perfused
sponges were contained in a glass column with medium flow set at 1.3 mL/min. In
some sponges, the 32D cl3 c-fms(m) (CRX-1) hematopoietic progenitor cell line was
added 7 days after GPIa cells. At 7 and 16 days, light microscopic evaluation
showed poor viability of cells in static sponge cultures. In perfused sponge
cultures, there was greater cellularity throughout the sponge and abundant
accumulation of metachromatic extracellular matrix surrounding GPIa cells.
Chondroitin 6-sulfate and heparan sulfate were identified as components of the
matrix by immunohistochemical methods. DNA synthesis was evaluated by 15-h
exposure of cultures to bromodeoxyuridine (BrdU), with subsequent
immunohistochemical localization with monoclonal anti-BrdU antibody. Cells
positive for BrdU were identified at the outer surfaces of both static and
perfused sponges; however, positive cells were also seen throughout the internal
areas of the sponges that were perfused. These results suggest that better
nutrient exchange occurred in perfused sponges. In static cocultures of GPIa and
CRX-1 cells, there was no detectable viability of the IL-3-dependent CRX-1 cells;
however, under perfused conditions, CRX-1 cells flourished within the sponges as
documented by BrdU incorporation. Thus, medium perfusion enhanced GPIa stromal
cell line viability and function in 3D collagen sponge cultures, as demonstrated
by BrdU incorporation, matrix production, and support of CRX-1 cells. This novel
culture system may be useful for examining the interactions of bone marrow
stromal cells with extracellular matrix molecules, soluble and matrix-bound
factors, and with other cell types.
PMID- 9647442
TI - Measurement of myocardial infarct size by electron beam computed tomography: a
comparison with 99mTc sestamibi.
AB - RATIONALE AND OBJECTIVES: The authors sought to determine, using a variety of
regional left ventricular ejection fraction (EF) and wall thickening (WTh)
criteria, the applicability to measure left ventricular (LV) infarct size using
electron-beam CT (EBCT) in patients as compared with technetium 99m (99mTc)
sestamibi scanning as reference standard. METHODS: Twelve patients (age 57 +/- 11
years) underwent 99mTc sestamibi scanning and EBCT at hospital discharge after an
acute index anterior myocardial infarction. Left ventricular infarct size was
defined using standard 99mTc sestamibi scanning. Regional EF and WTh were
analyzed on each EBCT scan with use of a floating epicardial centroid method. In
five contiguous LV tomograms, the amount of infarcted myocardium was estimated
using the following EF and WTh criteria: EF < or = 35%, 30%, 25%, 20%, and WTh <
or = 2 mm, 1 mm, and 0 mm. RESULTS: Infarct size measured with 99mTc sestamibi
was 33.3% (+/- 18.3%) (mean +/- SD, range 6%-54%) of the LV. Using an EF < or =
35% or absolute WTh < or = 2 mm as criteria for infarcted myocardium, EBCT
yielded 28% (+/- 17%) and 27% (+/- 16%), respectively (P = NS, paired Student's t
test, versus 99mTc sestamibi). Although, with use of the other criteria, EBCT
tended to underestimate infarct size compared with 99mTc sestamibi, a close
correlation across the entire range of infarct size determinations (range, 0.72
0.82) regardless of the underlying criteria suggested an internal consistency of
the data. CONCLUSIONS: Quantitative analysis of regional myocardial function by
EBCT allows an estimate of anterior infarct size when compared with 99mTc
sestamibi. This suggests that in addition to previously established applications
after acute myocardial infarction such as examination of cardiac volumes and
mass, EBCT also may provide for infarct size determination.
PMID- 9647443
TI - A new model of endovascularly induced renal artery stenosis in
normocholesterolemic versus hypercholesterolemic rabbits.
AB - RATIONALE AND OBJECTIVES: The authors determine the feasibility of creating renal
artery stenosis by overdilatation and deendothelialization and compare the model
in normocholesterolemic versus hypercholesterolemic rabbits. METHODS: Thirty male
New Zealand White rabbits were randomized into two groups: group A (n = 15) was
fed a normal diet and group B (n = 15) was fed a cholesterol-rich diet 4 weeks
before stenosis induction. An aortogram was performed, then the right renal
artery was overdilated with an angioplasty balloon-catheter, and
deendothelialized. After 6 weeks, groups A and B were compared by angiographic
and pathologic study. RESULTS: Comparison of group A versus group B showed that
12 arteries (80%) versus 6 (40%) were angiographically stenotic (P < 0.05); 14
(93%) versus 12 (80%) contained neointima (NS), 12 (80%) versus 3 (20%) showed
medial disorganization (P < 0.01), and 9 (60%) versus 2 (13%) presented
adventitial fibrosis (P < 0.01). CONCLUSIONS: A new model of endovascularly
induced renal artery stenosis has been developed in rabbits. Medial proliferation
and adventitial fibrosis are more frequent in normocholesterolemic rabbits.
PMID- 9647444
TI - Dynamic phosphorus-31 magnetic resonance spectroscopy in arterial occlusive
disease: effects of vascular therapy on spectroscopic results.
AB - RATIONALE AND OBJECTIVES: The aim of the authors' prospective study was to
explore therapy-induced changes of muscular metabolism in arterial occlusive
disease (AOD). MATERIALS: Before and after vascular therapy, respectively, 31
patients with AOD were examined by dynamic phosphorus-31 (31P) magnetic resonance
spectroscopy (MRS) at 1.5 T; in the magnet, the quadriceps muscle was stressed by
an isometric and an isotonic form of exercise until exhaustion, respectively.
Twenty-three patients were treated by standardized percutaneous transluminal
angioplasty; eight patients underwent a vascular operation. RESULTS: Vascular
therapy induced a marked improvement of clinical and angiographic results. At the
same work load, exercise-induced metabolic changes of the quadriceps muscle were
significantly less pronounced after the vascular therapy: maxima of the ratio
inorganic phosphate (Pi)/phosphocreatine (PCr) (isometric exercise: 0.34 [after
therapy] versus 0.44 [before therapy]; isotonic exercise: 0.36 [after therapy]
versus 0.51 [before therapy]) as well as minima of pH (isometric exercise: 7.00
[after therapy] versus 6.93 [before therapy]; isotonic exercise: 7.00 [after
therapy] versus 6.93 [before therapy]). In relation to maximal values of Pi/PCr,
the extent of acidosis was smaller after vascular therapy, resulting in a flatter
slope of the regression line between these parameters (b = -0.24 +/- 0.10 versus
b = -0.31 +/- 0.09). After both of the exercises, time of half recovery of Pi/PCr
was significantly shorter after vascular therapy (isometric exercise: 43 seconds
[after therapy] versus 83 seconds [before therapy]; isotonic exercise: 42 seconds
[after therapy] versus 57 seconds [before therapy]). CONCLUSIONS: After effective
vascular therapy, minor exercise-induced metabolic changes (increased
"work/energy cost-index"), a decreased contribution of anaerobic glycolysis to
total adenosine triphosphate production as well as a markedly increased recovery
rate of Pi/PCr are unequivocal spectroscopic proofs of an improved oxidative
metabolism of muscle cells because of increased tissue perfusion.
PMID- 9647445
TI - Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial
magnetic stimulation.
AB - RATIONALE AND OBJECTIVES: The authors demonstrate the feasibility of combining
transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging
(fMRI) inside an MR scanner to noninvasively stimulate and image regional brain
activity. METHODS: Echoplanar blood oxygen level dependent (BOLD)-based fMRI
studies of TMS response were performed on three human volunteers inside a
standard 1.5 T MR scanner using independent computer control to interleave
echoplanar image acquisition and stimulation of right thumb primary motor cortex
with a nonferromagnetic TMS coil. RESULTS: Significant (P< 0.001) response was
observed in motor cortex under the TMS coil during stimulation compared to rest,
as well in auditory cortex, the latter presumably due to the loud "snap" when the
coil was pulsed. CONCLUSIONS: Concurrent TMS stimulation and echoplanar BOLD fMRI
imaging is possible. This method has potential for tracing neural circuits with
brain imaging, as well as investigating the effects of TMS.
PMID- 9647446
TI - Diagnostic evaluation of sonographically visualized breast lesions by using a new
clinical amplitude/velocity reference imaging technique (CARI sonography).
AB - RATIONALE AND OBJECTIVES: The goal of this study was to evaluate and
differentiate breast lesions in patients by sonographic measurements performed
using CARI sonography. METHODS: Thirty-one patients with 33 histologically proven
breast lesions were examined by mammography, conventional ultrasound sonography,
and CARI sonography. Investigation with mammography-like positioning was
performed in case of CARI sonography. The ratios of the lesion diameters were
calculated in a craniocaudal and a mediolateral plane. The results were compared
with the results obtained with conventional modalities. RESULTS: Breast lesions
were detected with the best sensitivity (100%) and a high specificity (86%) using
B-mode ultrasound sonography. Mammography resulted in a sensitivity of 92% and a
specificity of 91%, whereas the CARI sonography yielded 100% sensitivity and 67%
specificity. CONCLUSIONS: The differentiation of lesions by measurements
performed with CARI sonography resulted in a high sensitivity. The specificity,
however, was inferior compared with the other imaging modalities. This may limit
the routine application of the technique for clinical diagnoses of breast
lesions. However, due to the small number of patients investigated in this pilot
study, the full potential should be evaluated in a larger collective of patients.
PMID- 9647447
TI - Abdominal image segmentation using three-dimensional deformable models.
AB - RATIONALE AND OBJECTIVES: The authors develop a three-dimensional (3-D)
deformable surface model-based segmentation scheme for abdominal computed
tomography (CT) image segmentation. METHODS: A parameterized 3-D surface model
was developed to represent the human abdominal organs. An energy function defined
on the direction of the image gradient and the surface normal of the deformable
model was introduced to measure the match between the model and image data. A
conjugate gradient algorithm was adapted to the minimization of the energy
function. RESULTS: Test results for synthetic images showed that the
incorporation of surface directional information improved the results over those
using only the magnitude of the image gradient. The algorithm was tested on 21 CT
datasets. Of the 21 cases tested, 11 were evaluated visually by a radiologist and
the results were judged to be without noticeable error. The other 10 were
evaluated over a distance function. The average distance was less than 1 voxel.
CONCLUSIONS: The deformable model-based segmentation scheme produces robust and
acceptable outputs on abdominal CT images.
PMID- 9647448
TI - Influence of contrast media on the response of rat renal arteries to endothelin
and nitric oxide: influence of contrast media.
AB - RATIONALE AND OBJECTIVES: Contrast media (CM) such as diatrizoate meglumine (DTZ)
or iohexol can cause renal vasoconstriction in vivo, and this may initiate CM
induced nephropathy. Endothelin-1 (ET-1), a vasoconstrictor, and nitric oxide, a
vasodilator, are key modulators of renal circulation. We tested the hypothesis
that CM enhances arterial responses to ET-1, or diminishes responses to nitric
oxide. METHODS: A video dimension analyzer continuously recorded changes in
diameter of isolated, pressurized rat interlobar renal arteries (200-400 microm
diameter) superfused with combinations of CM, ET-1, nitric oxide, and other
vasoactive agents. RESULTS: Superfusion of arteries with 3.3% DTZ, but not with
3.3% iohexol, enhanced their sensitivity to ET-1 by approximately twofold, as
assessed by shifts in concentration-response curves. Both DTZ and iohexol
decreased the sensitivity of arteries to nitric oxide by approximately threefold.
Neither DTZ nor iohexol affected arterial sensitivity to other vasoconstrictors
(phenylephrine, potassium) or vasodilators (forskolin, diltiazem). CONCLUSIONS:
Diatrizoate meglumine and iohexol may induce or augment renal vasoconstriction in
part by causing selective alterations in arterial sensitivity to ET-1 and to
nitric oxide.
PMID- 9647449
TI - Are superabsorbers useful for endovascular embolization of saccular aneurysms? An
in vitro study.
AB - RATIONALE AND OBJECTIVES: The authors conducted in vitro evaluation of
superabsorber for endovascular embolization of saccular aneurysms. METHODS: The
swelling properties of the superabsorber Sanwet IM-7000 were investigated in
various solvents. The material used was granulate (group A: particle size
approximately 459 microm; group B: particle size approximately 20 microm) as well
as cubes with an edge length of 1 mm prepared from a block. With ascending
concentrations of Sanwet IM-7000 held in suspensions made of Lipiodol and 96%
ethanol, the injectability was determined using microcatheters (2.1 F/3 F). The
behavior of Sanwet IM-7000 as occlusion material for aneurysms was examined in a
sacciform glass-model aneurysm. RESULTS: The granule showed no significant
increase in size in Lipiodol and in 96% ethanol, so that they were chosen for
catheter measurement. In Lipiodol suspension the maximum fraction of the
granulate suitable for injection through a 3 F catheter was 3.2%. In 96% ethanol
suspension the maximum fraction of granulate suitable for injection through a 3 F
catheter was 0.8%. Suspended in Lipiodol Sanwet IM-7000 showed a moderate
swelling in the aneurysm model, whereas the use of 96% ethanol resulted in a
pronounced swelling of the granulate (100 vol%) after the 96% ethanol was washed
off. Irrespective of the granulate size used, a rinse-off process of the
granulate occurred in the model aneurysm at a flow rate above 200 mL x min(-1).
Cubes prepared from a block of the base polymerisate of Sanwet IM-7000 showed a
delayed increase in size. The final size in 0.9% NaCl solution was reached in the
cubes after 220 min, in the granulate already after 20 mins. The cubes displayed
a high form stability. CONCLUSIONS: Due to the substance-related absence of
intercorporeal cross-linking and the unpredictable increase in size, embolization
of aneurysms using Sanwet IM-7000 granulate is inadvisable at present. In spite
of a longer swelling time and because of its form consistency, the use of
prepared cubes could provide a reasonable alternative.
PMID- 9647450
TI - Review of the effectiveness of capsaicin for painful cutaneous disorders and
neural dysfunction.
AB - BACKGROUND: Topical capsaicin is known to be a safe and effective pain management
adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, and diabetic
neuropathy. However, studies and case reports in the literature have indicated
that other conditions may also benefit from capsaicin: painful or itching
cutaneous disorders from operations, injuries, or tumors; neural dysfunction; or
inflammation of the airways and urinary tract. METHODS: To determine the
effectiveness of capsaicin for painful cutaneous disorders and neural
dysfunction, the authors analyzed data from 33 reports (MEDLINE search of 1966
96) on the efficacy of capsaicin. Outcome measures consisted of the response rate
and degree of pain relief. Results from placebo-controlled trials were pooled
when possible; effect of treatment was estimated by the method of DerSimonian and
Laird. RESULTS: Pain relief for postmastectomy syndrome and cluster headache was
greater with capsaicin than with placebo; also, psoriasis and pruritus responded
better to capsaicin. Uncontrolled studies and case reports have indicated that
pain or dysfunction was less at the end of capsaicin therapy for neck pain, loin
pain/hematuria syndrome, oral mucositis, rhinopathy, reflex sympathetic dystrophy
syndrome, detrusor hyperreflexia, and cutaneous pain due to tumor of the skin.
CONCLUSIONS: Capsaicin is effective for psoriasis, pruritus, and cluster
headache; it is often helpful for the itching and pain of postmastectomy pain
syndrome, oral mucositis, cutaneous allergy, loin pain/hematuria syndrome, neck
pain, amputation stump pain, and skin tumor; and it may be beneficial for neural
dysfunction (detrusor hyperreflexia, reflex sympathetic dystrophy, and
rhinopathy). A universal problem for many of the studies analyzed was the absence
of a "burning placebo" such as camphor.
PMID- 9647451
TI - Social context of pain in children with Juvenile Primary Fibromyalgia Syndrome:
parental pain history and family environment.
AB - OBJECTIVE: The purpose of this study was to describe parental pain history and
the family environment as it relates to the functional status of children with
Juvenile Primary Fibromyalgia Syndrome (JPFS). DESIGN AND OUTCOME MEASURES:
Twenty-nine parents of children with JPFS completed a pain history questionnaire,
Von Korff Chronic Pain Grading system, and the Family Environment Scale (FES).
Twenty-one adolescents with JPFS completed the FES, the Visual Analogue Scale for
Pain, the modified Fibromyalgia Impact Questionnaire for Children, the Arthritis
Impact Measurement Scales, and the Symptom Checklist-90-Revised. Correlational
analyses were performed. RESULTS: Parents of children with JPFS reported multiple
chronic pain conditions, including but not limited to fibromyalgia. Parental pain
history and the family environment correlated with the health status of
adolescents with JPFS. Children with JPFS perceived the family environment as
significantly more cohesive than did their parents. Greater incongruence between
parent and child responses on the FES positively correlated with greater
impairment. CONCLUSIONS: These results suggest that family environment and
parental pain history ay be related to how children cope with JPFS. Behavioral
interventions targeting the family may improve the long-term functional status of
children with JPFS.
PMID- 9647452
TI - Children's self-report of postoperative pain intensity and treatment threshold:
determining the adequacy of medication.
AB - OBJECTIVE: Many studies have shown indirectly that children are undermedicated
for postoperative pain. In this study, we used a pain self-report scale to
examine this more directly. METHODS: We performed a survey with 63 children who
were postoperative from minor, uncomplicated surgery. Using the self-report
scale, we determined the pain intensity at time of interview, the worst pain
experienced postoperatively, and the intensity of pain that the subject felt to
warrant pharmacologic intervention (the "treatment threshold"). A subgroup of 48
children was asked to indicate on the scale the intensities that represented
mild, moderate, and severe pain. RESULTS: Mean (SD) pain at time of interview was
1.9 (1.7) on the 0-6 scale. Mean worst postoperative pain was 3.8 (1.8). The mean
for treatment threshold was 3.2 (1.8). We found gender differences in regard to
the judgments about the intensities representing mild, moderate, and severe pain,
with girls rating these lower than did boys. Twenty-five percent of subjects
reported pain that was mild, 29% reported moderate pain, and 46% reported severe
pain. CONCLUSIONS: We found that 51% of subjects were undermedicated for
postoperative pain, being required to suffer pain that was above their treatment
threshold. By determining each subject's treatment threshold and estimate of
moderate pain, we have better defined the intensity at which pain becomes
clinically significant.
PMID- 9647453
TI - Age as a factor in admission to chronic pain rehabilitation.
AB - OBJECTIVE: To examine access to multidisciplinary pain rehabilitation programs
for older patients. DESIGN: Telephone and written surveys of pain programs
accredited by Commission on Accreditation of Rehabilitation Facilities. Visual
Analog Scale (VAS) ratings of patient vignettes in which older patients were
alternatively assigned their true age or a younger age. PARTICIPANTS: Health care
professionals at pain programs. MAIN OUTCOME MEASURES: Telephone survey of
admission policies and treatment services. VAS ratings of patient vignettes.
RESULTS: No program excludes older pain patients by age. However, 28% of programs
had admitted only the youngest old (< 70 years). Age-related criteria, such as
presence of concurrent medical diagnoses that are more likely to exclude older
patients, are common. In addition, VAS ratings of patient vignettes indicated an
age bias: the same patients were rated as 14.8% less likely to be admitted (p <
.001) and 12.5% less likely to succeed if admitted (p < .001) when their true,
older age was given than when a false younger age was provided. CONCLUSION: Pain
program admission policies do not exclude older patients by age but frequently
include age-related criteria that disproportionately exclude the elderly. There
is also evidence of an age bias in which age per se reduces perceived suitability
for pain program admission.
PMID- 9647454
TI - Spontaneous onset of back pain.
AB - OBJECTIVES: To assess the frequency with which patients attribute low back pain
to spontaneous onset. DESIGN: A consecutive sample of two distinct groups of
patients seeking treatment for back pain: those without need to identify cause
(study group, n = 4,689) and those required to report a specific event to qualify
for benefits paid for by a third party (compensated group, n = 6,687). SETTING:
Active exercise-based back pain rehabilitation clinics. SUMMARY OF BACKGROUND
DATA: Research on the natural history of back pain has revealed frequent reports
of spontaneous recovery, usually within 8-12 weeks after onset. There is little
comparable literature pertaining to the report of spontaneous onset. METHODS:
Data were collected for two groups of consecutive patients who attended for
initial assessments of their back pain at 16 Canadian Back Institute locations,
between May 1, 1994 and February 28, 1995. Patient responses were collected using
a standardized, professionally administered questionnaire. RESULTS: In the group
without need to identify cause, 66.7% of patients could not identify an event
producing their symptoms. For those required to report a specific event, only
9.8% of patients failed to attribute cause. Multivariate logistic regression
revealed that the required-to-report group was approximately 15 times more likely
to report an event (odds ratio = 14.95; 95% confidence interval = 13.44, 16.65)
than the study group; those pursuing litigation were more than 2.5 times more
likely to report a causative event (odds ratio = 2.68; 95% confidence interval =
2.09, 3.49). CONCLUSIONS: Back pain occurred spontaneously in approximately 67%
of patients seeking treatment in the study group. The authors consider
spontaneous onset to be part of the natural history of back pain for this group.
PMID- 9647455
TI - Transcutaneous electrical nerve stimulation in the treatment of chronic pain:
predictive factors and evaluation of the method.
AB - OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) is a widely used
therapeutic approach in acute and chronic pain syndromes. The aim of this study
was to investigate the influence of patient management as well as other factors
on the outcome of TENS treatment. DESIGN: The study was carried out as a
retrospective analysis of the course of treatment and the therapeutic results of
transcutaneous electric nerve stimulation (TENS) in 482 patients with chronic
pain of various origins. The follow-up period was up to 48 months. Two groups
with differing patient management were compared. RESULTS: Competent patient
evaluation and education (i.e., a long testing and learning phase as well as
regular comprehensive after-care) was found to be important. Our analysis of the
reasons for the discontinuation of long-term TENS therapy showed that the most
important feature was the discrepancy between effort and therapeutic result.
Other causes were intermittent depressive states and progression of the
underlying disease followed by an aggravation of pain. In addition, numerous
factors were identified that adversely affected the outcome of TENS treatment.
These factors were listed in order of importance and were included in a
prognostic score. CONCLUSIONS: The prognostic score permits an efficient
selection of patients. Moreover, a comprehensive documentation of pain syndromes
and their organic, psychogenic, and social features is presented. On the basis of
this documentation, an appropriate therapeutic concept may be established. The
prognostic score was validated in a subsequent study including 99 patients with
chronic pain treated with TENS.
PMID- 9647456
TI - Stressful life events and psychological dysfunction in Complex Regional Pain
Syndrome type I.
AB - OBJECTIVE: To determine to what extent stressful life events and psychological
dysfunction play a role in the pathogenesis of Complex Regional Pain Syndrome
type I (CRPS). DESIGN: A comparative study between a CRPS group and a control
group. Stressful life events and psychological dysfunction evaluation was
performed with a life event rating list and the Symptom Checklist-90 (SCL-90).
SETTING: A university hospital. SUBJECTS: The CRPS group consisted of 24 patients
with a history of upper extremity CRPS of less than 3 months. The control group
consisted of 42 hand pathology patients waiting for elective hand surgery within
the next 24 hours. MAIN OUTCOME MEASURES: Stressful life event rating was
measured using the Social Readjustment Rating Scale. Psychological dysfunction
was measured using the SCL-90. RESULTS: Stressful life events were experienced by
19 patients (79.2%) in the CRPS group and by 9 patients (21.4%) in the control
group. This difference was significant. Testing of psychological dysfunction (SCL
90) in CRPS patients and the control group demonstrated some significant
differences: male patients were more anxious than male controls; female patients
were statistically more depressed, had feelings of inadequacy, and were
emotionally less stable than female controls. In multivariate analysis, no
significant differences were found across gender, age, or gender x group
interactions. Of the SCL-90 dimensions, only insomnia correlated with the
experienced stressful life events. CONCLUSION: Stressful life events are more
common in the CRPS group, which indicates that there may be a multiconditional
model of CRPS. The experience of stressful life events besides trauma or surgery
are risk factors, not causes, in such a model.
PMID- 9647457
TI - Symptoms of spinal stenosis do not improve after epidural steroid injection.
AB - OBJECTIVE: This study was carried out to evaluate the therapeutic effect of
epidural steroid injection on pseudoclaudication in patients with lumbar
degenerative spinal canal stenosis. DESIGN: Fifty-three patients who complained
of pseudoclaudication of less than 20 m in walking distance were randomly divided
into three groups. Group 1 (n = 16) underwent epidural injection with 8 ml of
saline. Group 2 (n = 18) underwent epidural block with 8 ml of 1% mepivacaine.
Group 3 (n = 19) underwent epidural block with a combination of 8 ml of 1%
mepivacaine and 40 mg of methylprednisolone. The criteria of evaluation were as
follows: excellent effect, > 100 m in walking distance; good effect, 20-100 m in
walking distance; poor effect, <20 m in walking distance. RESULTS: In group 1,
the numbers of patients who showed a good effect were two (12.5%) after 1 week,
one (6.5%) after 1 month, and one (6.5%) after 3 months. In group 2, the numbers
of patients who showed a good or excellent result were 10 (55.5%) after 1 week,
three (16.7%) after 1 month, and one (5.6%) after 3 months. In group 3, the
numbers of patients who showed a good or excellent result were 12 (63.2%) after 1
week, three (15.8%) after 1 month, and one (5.3%) after 3 months. There was no
significant difference in the effectiveness of treatment between group 2 and
group 3 throughout the time course. CONCLUSION: The results suggest that epidural
steroid injection has no beneficial effect on the pseudoclaudication associated
with spinal canal stenosis as compared with epidural block with a local
anesthetic alone.
PMID- 9647458
TI - Chest tube insertion: a prospective evaluation of pain management.
AB - OBJECTIVE: To evaluate pain associated with chest tube insertion in a group of
patients with malignant pleural effusions. DESIGN: Prospective case series.
SETTING: Acute care cancer center in an academic institution. PATIENTS: Fifty-two
patients with symptomatic malignant pleural effusions. Twenty-six evaluated by
conventional approach to chest tube insertion (group 1), 26 evaluated after
institution of a new chest tube protocol (group 2). INTERVENTIONS: A new protocol
was designed to improve pain control during chest tube insertion. The protocol
included improved housestaff and nursing education, premedication, proper
insertion techniques, and more liberal and precise delivery of local anesthetic.
OUTCOME MEASURES: Both groups were evaluated by a verbal self-report scale (1-10)
to assess pain and anxiety. RESULTS: The mean pain rating in group 1 was 6.2 (+/
0.76) compared with 3.7 (+/-5.6) in group 2 (p < 0.01). In group 1, pain or
anxiety was 9 or 10 in 12 of 26 on a scale of 1 to 10, compared with 2 of 26 in
group 2 (p < 0.001). Anxiety rating was 4.5 (+/-0.72) in group 1 compared with
1.5 (+/-0.54) in group 2 (p < 0.01). CONCLUSIONS: Chest tube insertion was
associated with an unacceptably high level of pain and anxiety in our hospital. A
new protocol, including housestaff education and changes in nursing policies,
technical aspects, local anesthetic dose and delivery, and pre-medication,
allowed us to approach the goal of a painless chest tube insertion.
PMID- 9647459
TI - Complex Regional Pain Syndromes: guidelines for therapy.
AB - This report aims to present an orderly approach to the treatment of Chronic
Regional Pain Syndrome (CRPS) types I and II through an algorithm. The central
theme is functional restoration: a coordinated but progressive approach that
introduces each of the treatment modalities needed to achieve both remission and
rehabilitation. Reaching objective and measurable rehabilitation goals is an
essential element. Specific exercise therapy to reestablish function after
musculoskeletal injury is central to this functional restoration. Its application
to CRPS is more contingent on varying rates of progress that characterize the
restoration of function in patients with CRPS. Also, the various modalities that
may be used, including analgesia by pharmacologic means or regional anesthesia or
the use of neuromodulation, behavioral management, and the qualitatively
different approaches that are unique to the management of children with CRPS, are
provided only to facilitate functional improvement in a stepwise but methodical
manner. Patients with CRPS need an individual approach that requires extreme
flexibility. This distinguishes the management of these conditions from other
well-described medical conditions having a known pathophysiology. In particular,
the special biopsychosocial factors that are critical to achieving a successful
outcome are emphasized. This algorithm is a departure from the contemporary
heterogeneous approach to treatment of patients with CRPS. The underlying
principles are motivation, mobilization, and desensitization facilitated by the
relief of pain and the use of pharmacologic and interventional procedures to
treat specific signs and symptoms. Self-management techniques are emphasized, and
functional rehabilitation is the key to the success of this algorithm.
PMID- 9647460
TI - Hypnosis after an adverse response to opioids in an ICU burn patient.
AB - OBJECTIVE: Burn injuries produce severe wound care pain that is ideally
controlled on intensive burn care units with high-dosage intravenous opioid
medications. We report a case illustrating the use of hypnosis for pain
management when one opioid medication was ineffective. SETTING: Intensive burn
care unit at a regional trauma center. PATIENT: A 55-year-old man with an
extensive burn suffered from significant respiratory depression from a low dosage
of opioid during wound care and also experienced uncontrolled pain. INTERVENTION:
Rapid induction hypnotic analgesia. OUTCOME MEASURES: Verbal numeric pain scale,
and pain and anxiolytic medication usage. RESULTS: The introduction of hypnosis,
supplemented by little or no opioids, resulted in excellent pain control, absence
of need for supplemental anxiolytic medication, shortened length of wound care,
and a positive staff response over a 14-day period. CONCLUSIONS: This case
illustrates that hypnosis can not only be used easily and quite appropriately in
a busy medical intensive care unit environment, but that sometimes this treatment
may be a very useful alternative when opioid pain medication proves to be
dangerous and ineffective. This case also illustrates possible clinical
implications both pain relief and side-effect profiles for opioid receptor
specificity. Although this report does not provide data regarding hypnotic
mechanisms, it is clear that with some patients nonopioid inhibitory mechanisms
can be activated in a highly effective manner, that clinical context may be
important for the activation of those pathways, and that those mechanisms may be
accessed more easily than opioid mechanisms.
PMID- 9647461
TI - Cerebrospinal fluid pressure and acetazolamide treatment in idiopathic low back
pain.
PMID- 9647462
TI - Curcumin attenuation of acute adriamycin myocardial toxicity in rats.
AB - The protective effect of curcumin on acute adriamycin (ADR) myocardial toxicity
was analysed in rats. ADR toxicity, induced by a single intraperitoneal injection
(30 mg kg(-1)), was revealed by elevated serum creatine kinase (CK) and lactate
dehydrogenase (LDH). The level of the lipid peroxidation products, conjugated
dienes and malondialdehyde, was markedly elevated by ADR. ADR caused a decrease
in myocardial glutathione content and glutathione peroxidase activity. In
contrast, cardiac catalase activity was increased in ADR rats. Curcumin treatment
(200 mg kg(-1), seven days before and two days following ADR) significantly
ameliorated the early manifestation of cardiotoxicity (ST segment elevation and
an increase in heart rate) and prevented the rise in serum CK and LDH exerted by
ADR. ADR rats that received curcumin displayed a significant inhibition of lipid
peroxidation and augmentation of endogenous antioxidants. These results suggest
that curcumin inhibits ADR cardiotoxicity and might serve as novel combination
chemotherapeutic agent with ADR to limit free radical-mediated organ injury.
PMID- 9647463
TI - Molecular cloning and characterization of rat P2Y4 nucleotide receptor.
AB - An intronless open reading frame encoding a protein (361aa in length) was
isolated from a rat genomic library probed with a DNA fragment from rat heart.
This protein showed 83% sequence identity with the human P2Y4 (hP2Y4) receptor
and represents a homologue of the human pyrimidinoceptor. However, the rP2Y4
receptor is not selective for uridine nucleotides and, instead, shows an agonist
potency order of ITP = ATP = ADP(pure) = UTP = ATPgammaS = 2-MeSATP = Ap4A >
UDP(pure). ADP, ATPgammaS, 2-MeSATP and UDP are partial agonists. Thus, in terms
of agonist profile, rP2Y4 is more like the P2U receptor subtype. The rP2Y4
receptor was reversibly antagonized by Reactive blue 2 but not by suramin which,
otherwise, inhibits the hP2Y2 receptor (a known P2U receptor). Thus, rP2Y4 and
the P2Y2 subtype appear to be structurally distinct forms of the P2U receptor
(where ATP and UTP are equi-active) but can be distinguished as suramin
insensitive and suramin-sensitive P2U receptors, respectively.
PMID- 9647464
TI - Effects of steroid treatment on activation of nuclear factor kappaB in patients
with inflammatory bowel disease.
AB - Nuclear factor kappB (NFkappaB) is a transcription factor that controls several
genes important for immunity and inflammation. The aim of this study was to
assess if activation of NFkappaB plays a role in the pathogenesis of inflammatory
bowel disease (IBD), and whether steroid treatment affects NFkappaB activation.
Activation of NFkappaB was analysed in colon biopsy samples of 13 patients with
active IBD (8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility
shift assays, under basal conditions and 3 weeks after treatment with 0.75 mg kg(
1) day(-1) prednisolone. The presence of interleukin-8 mRNA in biopsies was
assessed by RT-PCR. A specific NFkappaB band was present in all nuclear extracts
from inflamed mucosa, whereas the band was barely detectable in uninflamed
colonic mucosa. NFkappaB bands were super-shifted by antibodies against p50
subunit, whereas antibodies against p65, p52, c-Rel, or Rel B did not modify the
mobility of the band. Increased interleukin-8 mRNA was detected at the same sites
of NFkappaB activation. Steroid-induced healing of colonic inflammation was
associated with disappearance of NFkappaB from nuclear extracts. These results
support the notion that NFkappaB plays an important role in the pathogenesis of
IBD, and that blockade of NFkappaB activation is one of the mechanisms by which
steroids suppress the inflammatory cascade in IBD.
PMID- 9647465
TI - Different actions of CCK on pancreatic and gastric growth in the rat: effect of
CCK(A) receptor blockade.
AB - 1. It is now well established that cholecystokinin (CCK) has a major
physiological role in the regulation of pancreatic secretion and gastro
intestinal (GI) motility. Both these actions are mediated by stimulation of
CCK(A)-receptors located on pancreatic acini and GI smooth muscle cells. While
chronic administration of CCK-like peptides invariably causes pancreatic
hypertrophy and hyperplasia, their action on gastric growth remains
controversial. 2. In the present investigation the action of exogenous and
endogenous CCK on both pancreatic and gastric growth was studied in the same
animal. In addition, the ability of dexloxiglumide, a new potent and selective
CCK(A)-receptor antagonist, to counteract CCK-mediated effects was evaluated. 3.
The amphibian peptide caerulein (1 microg kg(-1) intraperitoneally three times
daily) was used as a CCK agonist, while camostate (200 mg kg(-1) intragastrically
once daily), a synthetic protease inhibitor, was used to release endogenous CCK.
They were administered to rats for seven days with or without dexloxiglumide (25
mg kg(-1) subcutaneously 15 min before the stimulus). On the eighth day, animals
were killed, the pancreas and stomach excised, weighed, homogenized and their
protein and DNA content measured. 4. Both exogenous and endogenous CCK increased
the weight of the pancreas as well as the total pancreatic protein and DNA
content. Dexloxiglumide, which alone did not affect pancreatic size and
composition, was able to counteract both caerulein- and camostate-induced
pancreatic changes. Neither stimuli affected gastric growth in respect of weight
and composition of the oxyntic gland area and the antrum. 5. These results show
different effects of CCK on pancreatic and gastric growth. The CCK-induced
pancreatic hypertrophy and hyperplasia are blocked by the potent and specific
CCK(A)-receptor antagonist, dexloxiglumide. This compound therefore represents a
useful tool to investigate CCK-receptor interactions in peripheral organs.
PMID- 9647466
TI - Pharmacological characterization of a nonpeptide bradykinin B2 receptor
antagonist, FR165649, and agonist, FR190997.
AB - 1. The nonpeptide bradykinin (BK) B2 receptor antagonist, FR165649 (8-[2,6
dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N
methylamino]benzyloxy]-2-methylquinoline), and agonist, FR190997 (8-[2,6-dichloro
3-[N-[(E)-4-(N-methylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2
methyl-4-(2-pyridyl methoxy)quinoline) have been identified. These compounds have
a common chemical structure, and the 2-pyridylmethoxy group is the only
structural difference between them. 2. Both FR165649 and FR190997 displaced [3H]
BK binding to B2 receptors in guinea-pig ileum membranes, with an IC50 of 4.7 x
10(-10) M and 1.5 x 10(-9) M, respectively. They also displaced [3H]-BK binding
to B2 receptors in human lung fibroblast IMR-90 cells, with an IC50 of 1.6 x 10(
9) M and 9.8 x 10(-10) M, respectively. 3. In guinea-pig isolated ileum
preparations, FR165649 had no agonistic effect on contraction and caused parallel
rightward shifts of the concentration-response curves to BK on contraction.
Analysis of the data produced a nominal pA2 value of 9.2+/-0.1 (n=5) and a slope
of 1.4+/-0.1 (n=5). On the other hand, FR190997 induced concentration-dependent
contraction of guinea-pig ilea with a pD2 of 7.9+/-0.2 and the contraction was
inhibited by a specific peptide bradykinin B2 receptor antagonist, Hoe 140 (D-Arg
[Hyp3, Thi5, D-Tic7, Oic8]BK) in a non-competitive manner. 4. In IMR-90 cells,
FR165649 had no agonistic effect on phosphatidyl inositol (PI) hydrolysis and
caused parallel rightward shifts (approximately 200 fold shift at 10(-7) M) of
the concentration-response curves to BK on PI hydrolysis. FR190997 induced
concentration-dependent PI hydrolysis in IMR-90 cells with a pD2 of 8.4+/-0.1,
and this effect was inhibited by Hoe 140. 5. These results indicate that FR165649
and FR190997 are, respectively, a potent bradykinin B2 receptor antagonist and
agonist, and that the agonistic activity depends on the small part of the
nonpeptide ligand. FR165649 and FR190997 may be useful tools for studying the
relationship between ligands and receptors.
PMID- 9647467
TI - Role of reactive oxygen species in the signalling cascade of cyclosporine A
mediated up-regulation of eNOS in vascular endothelial cells.
AB - 1. Cyclosporine A (CsA) increases eNOS mRNA expression in bovine cultured aortic
endothelial cells (BAEC). As some effects of CsA may be mediated by reactive
oxygen species (ROS), present experiments were devoted to test the hypothesis
that the CsA-induced eNOS up-regulation could be dependent on an increased
synthesis of ROS. 2. CsA induced a dose-dependent increase of ROS synthesis, with
the two fluorescent probes used, DHR123 (CsA 1 microM: 305+/-7% over control) and
H2DCFDA (CsA 1 microM: 178+/-6% over control). 3. Two ROS generating systems,
xanthine plus xanthine oxidase (XXO) and glucose oxidase (GO), increased the
expression of eNOS mRNA in BAEC, an effect which was maximal after 8 h of
incubation (XXO: 168+/-21% of control values. GO: 208+/-18% of control values).
The ROS-dependent increased eNOS mRNA expression was followed by an increase in
eNOS activity. 4. The effect of CsA on eNOS mRNA expression was abrogated by
catalase, and superoxide dismutase (SOD). In contrast, the antioxidant PDTC
augmented eNOS mRNA expression, both in basal conditions and in the presence of
CsA. 5. The potential participation of the transcription factor AP-1 was
explored. Electrophoretic mobility shift assays were consistent with an increase
in AP-1 DNA-binding activity in BAEC treated with CsA or glucose oxidase. 6. The
present results support a role for ROS, particularly superoxide anion and
hydrogen peroxide, as mediators of the CsA-induced eNOS mRNA up-regulation.
Furthermore, they situate ROS as potential regulators of gene expression in
endothelial cells, both in physiological and pathophysiological situations.
PMID- 9647468
TI - Activation of midbrain presumed dopaminergic neurones by muscarinic cholinergic
receptors: an in vivo electrophysiological study in the rat.
AB - 1. Extracellular single-unit recording and iontophoresis were used to examine the
effects of different cholinoceptor agonists and antagonists on the firing rate
and firing pattern of A9 and A10 presumed dopaminergic neurones in the
anaesthetized rat. 2. Administration of low currents (1-5 nA) of the selective
muscarinic agonists oxotremorine M (Oxo M) and muscarine and of the non-selective
muscarinic/nicotinic agonist carbamylcholine (CCh) produced a dose-dependent
increase in firing rate in most of the A9 and A10 presumed dopaminergic neurones
tested. Oxo M-induced activation could be completely blocked by iontophoretic
application of the muscarinic antagonist butyl-scopolamine or systemic
administration of the muscarinic antagonist scopolamine (300 microg kg(-1),
i.v.). 3. Iontophoretic application of the selective nicotinic agonist
methylcarbamylcholine (MCCh), but not nicotine, induced a consistent increase in
firing rate. Surprisingly, the excitatory effect of MCCh was significantly
reduced by the selective muscarinic antagonist scopolamine (300 microg kg(-1),
i.v.), but not by the selective nicotinic antagonist mecamylamine (2.2 mg kg(-1),
i.v.). Mecamylamine (3 mg kg(-1), i.v.) was also ineffective in reducing the CCh
induced activation of presumed dopamine neurones, suggesting that both CCh and
MCCh increased the activity of dopamine neurones via an interaction with
muscarinic receptors. 4. Iontophoretic application of the endogenous agonist
acetylcholine (ACh) had no or little effect on the firing activity of A10
presumed dopaminergic neurones. However, concomitant application of neostigmine,
a potent cholinesterase inhibitor, with acetylcholine induced a substantial
activation of these neurones. This activation consisted of two components; one,
which was prevalent, was scopolamine (300 microg kg(-1), i.v.)-sensitive, and the
other was mecamylamine (2 mg kg(-1), i.v.)-sensitive. 5. In addition to their
effect on firing activity, Oxo M, muscarine and concomitant neostigmine/ACh
caused a significant increase in burst firing of A10 neurones, but not of A9
neurones. 6. These data suggest that dopamine cells, both in the A9 and A10
regions, possess functional muscarinic receptors, the activation of which can
increase their firing rate and, for A10 neurones, their amount of burst activity.
These cholinoceptors would be able to influence the activity of the midbrain
dopamine system greatly and may play a role in, and/or be a therapeutic target
for, brain disorders in which dopamine is involved (e.g., Parkinson's disease,
drug addiction and schizophrenia).
PMID- 9647469
TI - Ruthenium red as an effective blocker of calcium and sodium currents in guinea
pig isolated ventricular heart cells.
AB - 1. The effect of ruthenium red on calcium and sodium currents was studied in
guinea-pig isolated ventricular heart cells with the whole cell patch-clamp
technique. 2. Ruthenium red very efficiently blocked the L-type calcium current
in a dose-dependent manner. A significant block was observed for concentrations
as low as 0.3 microM. Analysis of the dose-response curve with the logistic
equation indicated an EC50 of 0.8 microM, a maximum inhibition of 85% reached at
5 microM, and a coefficient of 2.37. 3. There was no shift in the voltage
dependence of the Ca current activation, nor in that of its steady-state
inactivation determined with a 1 s prepulse. However, removal of Ca current
inactivation at positive voltage was considerably reduced in the presence of
concentrations of ruthenium red above 1 microM. A slowing of the time-course of
inactivation of the Ca current was also observed. 4. At 10 microM, a
concentration generally used to block the sarcoplasmic Ca release channels or the
mitochondrial Ca uptake, ruthenium red blocked 26.7+/-4.3% (n=8) of the sodium
current, and slowed its inactivation time-course. No effect was observed on the
voltage-dependence of the current activation or inactivation. The peak sodium
current was also decreased at a 10 times lower concentration by 7.6+/-2.7% (n=3).
5. Thus, at concentrations used to assess intracellular Ca movements, ruthenium
red induced in heart cells a significant block of both Ca and Na channels.
PMID- 9647470
TI - Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric
arteries and the involvement of beta-adrenoceptors.
AB - 1. The aim of the present study was to explore the contribution of adrenergic,
sensory and nitrergic innervations to the inhibitory effects of the beta2
adrenoceptor agonist clenbuterol on responses to electrical field stimulation
(EFS, 200 mA, 0.3 ms, 1-16 Hz, for 30 s, at 1 min interval) in rat mesenteric
artery segments without endothelium and the possible involvement of adrenergic,
sensory and nitrergic innervations. 2. Clenbuterol (1 microM) reduced EFS-induced
contractile responses, and this effect was reversed by the beta-antagonist
propranolol (1 microM) (contraction at 16 Hz expressed as % of 75 mM K+-induced
contraction was: control, 69+/-9, clenbuterol, 31+/-6, n=13, P<0.001; control,
83+/-5, clenbuterol+propranolol 70+/-7, n=11, P>0.05). 3. In arteries
preincubated with [3H]-noradrenaline (NA), clenbuterol did not modify the tritium
overflow evoked by EFS (200 mA, 0.3 ms, 4 Hz, for 60 s; ratio between tritium
release in the second and first stimuli was: control, 0.80+/-0.05 and clenbuterol
added before second stimulus, 0.91+/-0.11, n=5, P>0.05). 4. The nitric oxide (NO)
synthase inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine
methyl ester (L-NAME) (10 and 100 microM), and the guanylate cyclase inhibitor
methylene blue (10 microM) increased the contractions caused by EFS (%
contraction at 16 Hz, control, 81+/-7, n=26; 10 microM L-NMMA, 109+/-12, n=8,
P<0.05; methylene blue, 119+/-6, n=6, P<0.05). However, these contractions were
decreased by the NO synthase substrate L-arginine 10 microM (14+/-6%, n=6,
P<0.001), but not modified by either the sensory neurones toxin capsaicin (0.5
microM, 75+/-6%, n=6, P>0.05) or the protein synthesis inhibitor cycloheximide
(10 microM, 83+/-6%, n=8, P>0.05). None of these drugs altered the concentration
response curves to exogenous NA (n=7). 5. Pretreatment with capsaicin or
cycloheximide did not modify the reduction of the EFS-evoked contraction provoked
by clenbuterol. However the presence of L-NMMA (or L-NAME) or methylene blue did
decrease the effect of clenbuterol (% contraction at 16 Hz, clenbuterol, 31+/-6,
n=13; clenbuterol+10 microM L-NMMA, 93+/-11, n=8, P<0.05; clenbuterol+methylene
blue, 90+/-7, n=6, P<0.05). 6. These results suggest that the reduction caused by
clenbuterol in the contraction induced by EFS in rat mesenteric arteries seems to
be mediated by NO release, through the activation of beta2-adrenoceptors probably
present on nitrergic nerves.
PMID- 9647471
TI - Role of hyperthermia in the protective action of clomethiazole against MDMA
('ecstasy')-induced neurodegeneration, comparison with the novel NMDA channel
blocker AR-R15896AR.
AB - 1. The immediate effect of administration of 3,4-methylenedioxymethamphetamine
(MDMA or 'ecstasy') on rectal temperature and the effect of putative
neuroprotective agents on this change has been examined in rats. The influence of
the temperature changes on the long term MDMA-induced neurodegeneration of
cerebral 5-hydroxytryptamine (5-HT) nerve terminals was also examined. 2. The
novel low affinity N-methyl-D-aspartate (NMDA) receptor channel blocker AR
R15896AR (20 mg kg(-1), i.p.) given 5 min before and 55 min after MDMA (15 mg kg(
1), i.p.) did not prevent the MDMA-induced hyperthermia and did not alter either
the MDMA-induced neurodegenerative loss of 5-HT and 5-hydroxyindoleacetic acid (5
HIAA) in cortex, striatum and hippocampus or loss of [3H]-paroxetine binding in
cortex 7 days later. 3. The neuroprotective agent clomethiazole (50 mg kg(-1),
i.p.) given 5 min before and 55 min after MDMA (15 mg kg(-1)) abolished the MDMA
induced hyperthermic response and markedly attenuated the loss of 5-HT, 5-HIAA
and [3H]-paroxetine binding in the brain regions examined 7 days later. 4. When
rats treated with MDMA plus clomethiazole were kept at high ambient temperature
for 5 h post-MDMA, thereby keeping their body temperature elevated to near that
seen in rats given MDMA alone, the MDMA-induced loss of 5-HT, 5-HIAA and [3H]
paroxetine was still attenuated. However, the protection (39%) afforded by the
clomethiazole administration was less than seen in rats kept at normal ambient
temperature (75%). 5. These data support the proposals of others that NMDA
receptor antagonists are neuroprotective against MDMA-induced degeneration only
if they induce hypothermia and further suggest that increased glutamate activity
may not be involved in the neurotoxic action of MDMA. 6. These data further
demonstrate that a proportion of the neuroprotective action of clomethiazole is
due to an effect on body temperature but that, in addition, the compound protects
against MDMA-induced damage by an unrelated mechanism.
PMID- 9647472
TI - Pharmacological characterization of the human melatonin Mel1a receptor following
stable transfection into NIH3T3 cells.
AB - 1. Mouse fibroblasts (NIH3T3) transfected with the full-length coding region of
the Mel1a melatonin receptor stably expressed the receptor, coupled to a
pertussis toxin-sensitive G-protein(s) and exhibiting high affinity and adequate
pharmacological profile. 2. The receptor protein had the tendency of a strong
coupling to the G-protein and therefore low-affinity state was induced by
uncoupling the receptor from its G-protein in presence of high concentrations of
NaCl (500-700 mM) and/or GTPgammaS (100 microM). Thereafter, the affinity of a
series of melatonin analogues was determined to both, high- and low-affinity
receptor states, thus providing a basis for the prediction of their efficacy,
according to the ternary complex model. 3. The cells were subsequently used to
study the agonist-induced G-protein activation, determined by calculating the
rate of GDP-GTP exchange measured in presence of 35S-labelled GTPgammaS. The
natural ligand melatonin induced a significant increase in the GDP-GTP exchange
rate, the presence of GDP and NaCl being necessary to observe this effect. 4. The
full agonists 2-phenylmelatonin, 2-bromomelatonin and 6-chloromelatonin equally
induced an increase of the GDP-GTP exchange. 5-Hydroxy-N-acetyltryptamine
activated the GTP-GDP exchange to a much lesser extent (53%) than melatonin, thus
behaving as a partial agonist. As predicted by the model, the melatonin
antagonist (N-[(2-phenyl-1H-indol-3-yl)ethyl]cyclobutanecarboxamide) was without
effect on basal G protein activation. Coincubation of this compound with
melatonin induced a dose-dependent rightward shift in the melatonin concentration
effect curve, thus exhibiting the behaviour of a competitive and surmountable
antagonist. 5. Using the equation proposed by Venter (1997) we were able to
determine that there were no 'spare' receptors in the system. Therefore, the
approach proposed in the present work can be successfully used for the
determination of 'drug action' at the level of the human Mel1a melatonin receptor
and evaluation of the efficacy of new selective melatonin analogues.
PMID- 9647473
TI - Effects of tumour necrosis factor-alpha on the coronary circulation of the rat
isolated perfused heart: a potential role for thromboxane A2 and sphingosine.
AB - 1. The actions of tumour necrosis factor-alpha (TNF-alpha) on the coronary
circulation were investigated in the rat isolated heart, perfused under constant
flow, recirculating conditions. 2. An early increase in coronary perfusion
pressure (CPP) was observed upon treatment with TNF-alpha (increase in CPP 10 min
after TNF-alpha treatment: 45+/-12 mmHg vs control: 15+/-4 mmHg, P<0.05). The
role of sphingosine, prostanoids and endothelins, in this coronary constrictor
action, was investigated with the use of pharmacological inhibitors and
antagonists. 3. The TNF-alpha induced increase in coronary tone was blocked by
indomethacin, 10 microM (increase in CPP after 10 min: 13+/-4 mmHg vs TNF-alpha
alone, P<0.05). 4. The thromboxane receptor antagonist GR32191, 10 microM,
attenuated the TNF-alpha induced coronary constriction (12+/-2 mmHg vs TNF-alpha
alone, P<0.05), as did the joint thromboxane A2 synthesis inhibitor and receptor
antagonist ZD1542, 10 microM (8+/-1 mmHg vs TNF-alpha alone, P<0.05). 5. The
ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, also blocked the TNF
alpha induced response (8+/-4 mmHg vs TNF-alpha alone, P<0.05). 6. In contrast,
the coronary constrictor action of TNF-alpha was not inhibited by the
endothelinA/B receptor antagonist bosentan, 3 microM (38+/-9 mmHg vs TNF-alpha,
P=NS). 7. These data indicated that the early coronary vasoconstriction induced
by TNF-alpha was mediated by both thromboxane A2 and sphingosine, suggesting an
interaction between both the sphingomyelinase and phospholipase A2 metabolic
pathways.
PMID- 9647474
TI - Endothelin receptor subtypes and their functional relevance in human small
coronary arteries.
AB - 1. The potent constrictor peptide endothelin (ET) has been implicated in various
cardiovascular disorders including myocardial infarction and atherosclerosis. We
have investigated the nature of ET receptor subtypes present on human small
coronary arteries. 2. Small coronary arteries were mounted in a wire-myograph for
in vitro pharmacology. To investigate the ET receptor subtypes present in
different segments of the coronary vascular tree, arteries were grouped according
to internal diameter. Responses in arteries with small internal diameters (mean
316.7+/-7.9 microm; Group B) were compared to those in larger arteries (mean
586.2+/-23.1 microm; Group A). 3. ET-1 consistently and potently contracted
arteries from Group A and B, with EC50 values of 1.7 (0.9-3.2) nM (n=15) and 2.3
(1.4-4.2) nM (n=14), respectively. No correlation was observed between ET-1
potency and internal diameter. The response to ET-1 was potently antagonized by
the selective ET(A) receptor antagonist PD156707 in both Group A and Group B,
yielding pA2 values of 8.60+/-0.12 (n=4-6) and 8.38+/-0.17 (n=4-6), respectively.
Slopes from Schild regression were not significantly different from unity. 4. In
contrast to ET-1, individual responses to ET-3 were variable. While all arteries
from Group A responded to ET-3 (EC50 approximately 69 (23-210) nM) (n=12), no
response was obtained in 5 of the 14 tested in Group B. Of those responding, many
failed to reach a maximum at concentrations up to 1 microM. ET-1 was more potent
than ET-3 in all arteries tested. A biphasic ET-3 response was observed in 8
arteries suggesting that a small ET(B) population was also present in some
patients. The selective ET(B) receptor agonist sarafotoxin S6c had little or no
effect up to 10 nM (n=4-6). 5. Responses to ET-1 and ET-3 were unaffected by
removal of the endothelium in arteries from both groups suggesting a lack of
functional, relaxant ET(B) receptors on endothelial cells (n=5). 6. Using
autoradiography, specific high density binding of the non-selective, ET(A)/ET(B)
ligand [125I]-ET-1 and selective ET(A) ligand [125I]-PD151242 was detected on the
vascular smooth muscle layer of small intramyocardial coronary arteries (n=5). In
contrast, little or no binding of the selective ET(B) receptor ligand [125I]
BQ3020 was observed (n=5). Similarly, [125I]-ET-1 binding to vascular smooth
muscle was absent in the presence of the selective ET(A) receptor antagonist
PD156707. 7. We conclude that human small epi- and intramyocardial coronary
arteries express predominantly ET(A) receptors and it is these receptors which
mediate ET-induced contractions. A constrictor ET(B) receptor population may
exist in some patients. However, these receptors may have a limited role as
contractions to ET-1 can be blocked fully by the selective ET(A) receptor
antagonist PD156707.
PMID- 9647475
TI - Depression of NMDA receptor-mediated synaptic transmission by four alpha2
adrenoceptor agonists on the in vitro rat spinal cord preparation.
AB - 1. Alpha2-adrenoceptor agonists have a spinal site of analgesic action. In the
current study the synaptic depressant actions of xylazine, detomidine, romifidine
and dexmedetomidine have been compared on segmental reflexes containing NMDA
receptor-mediated components in the neonatal rat hemisected spinal cord
preparation in vitro. 2. Reflexes were evoked in the ventral root following
either supramaximal electrical stimulation of the corresponding ipsilateral
lumbar dorsal root to evoke the high intensity excitatory postsynaptic potential
(e.p.s.p.) involving all primary afferent fibres, or low intensity stimulation to
evoke the solely A fibre-mediated low intensity e.p.s.p. The high intensity
e.p.s.p. contains a greater NMDA receptor-mediated component. 3. Xylazine,
romifidine, detomidine and dexmedetomidine all depressed both the high intensity
e.p.s.p. and the low intensity e.p.s.p. giving respective EC50 values of 0.91+/
0.2 microM (n=12), 23.4+/-3 nM (n=12), 37.7+/-7 nM (n=8) and 0.84+/-0.1 nM (n=4)
for depression of the high intensity e.p.s.p. and 0.76+/-0.1 microM (n=12),
22.0+/-3 nM (n=12), 24.9+/-6 nM (n=4) and 2.7+/-0.6 nM (n=4) for depression of
the low intensity e.p.s.p., respectively. Unlike the other three drugs, the two
values for dexmedetomidine, showing a greater selectivity for the high intensity
e.p.s.p., are significantly different. 4. Each of these depressant actions was
reversed by the selective alpha2-adrenoceptor antagonist atipamezole (1 microM).
5. In contrast to previous reports of the actions of alpha2-adrenoceptor agonists
on the in vitro spinal cord preparation, at concentrations ten fold higher than
the above EC50 values xylazine, romifidine, detomidine and dexmedetomidine
depressed the initial population spike of motoneurons (MSR). This depression was
not reversed by atipamezole. 6. Comparison of the rank order of the present EC50
values for depression of the high intensity e.p.s.p. with potency ratios from in
vivo analgesic tests in previous studies show a close correlation between the
present in vitro tests and analgesic potency. There is no correlation between the
present data and previously obtained affinities of the agonists at non-adrenergic
imidazoline binding sites. 7. The current findings therefore suggest that
xylazine, romifidine, detomidine and dexmedetomidine are exerting their central
analgesic actions at the spinal level principally through alpha2-adrenoceptors.
All four agonists showed the same profile of selective depression of the NMDA
receptor-mediated component of reflexes similar to that reported previously for
clonidine. However dexmedetomidine, unlike the other ligands, selectively
depressed the high intensity e.p.s.p.
PMID- 9647476
TI - Characterization of prostanoid receptor-evoked responses in rat sensory neurones.
AB - 1. Prostanoid receptor-mediated sensitization, or excitation, of sensory nerve
fibres contributes to the generation of hyperalgesia. To characterize the
prostanoid receptors present on sensory neurones, biochemical assays were
performed on primary cultures of adult rat dorsal root ganglia (DRG) and the F-11
(embryonic rat DRG x neuroblastoma hybrid) cell line. 2. In DRG cultures, the IP
receptor agonists, cicaprost and carbaprostacyclin (cPGI2) stimulated cyclic AMP
accumulation. Prostaglandin E2 (PGE2) also increased cyclic AMP levels, but to a
lesser extent, while carbocyclic thromboxane A2 (cTxA2), PGD2 and PGF2alpha had
negligible effects. The rank order of agonist potency was
cicaprost>PGE2=BMY45778=cPGI2=PGI2. In the F-11 cells, the rank order of agonist
potency for the stimulation of cyclic AMP accumulation was:
cicaprost>iloprost=cPGI2=PGI2=BMY45778>PGE2=cTXA2++ +. In DRG cultures, cicaprost
induced significantly more accumulation of inositol phosphates than PGE2. 3. To
examine the effects of prostanoids on C-fibre activity, extracellular recordings
of d.c. potentials from the rat isolated vagus nerve were made with the 'grease
gap' technique. PGI2 (0.1 nM-10 microM) produced the largest depolarizations of
the nerve. The rank order of agonist potency was:
PGI2=cPGI2=PGE1>cTXA2>PGE2=PGD2=TXB2>PGF2alpha. 4. Prior depolarization of nerves
with either forskolin (10 microM) or phorbol dibutyrate (1 microM) alone
significantly reduced the response to PGI2 (10 microM), while simultaneous
application of both forskolin and phorbol dibutyrate attenuated PGI2 responses
almost completely. 5. Putative EP1 and/or TP receptor-selective antagonists had
no effect on the responses to PGI2, cPGI2 or PGE2 in the three preparations
studied. 6. Collectively, these data are consistent with a positive coupling of
IP receptors to both adenylyl cyclase and phospholipase C in sensory neurones.
These findings suggest that IP receptors play a major role in the sensitization
of rat sensory neurones.
PMID- 9647477
TI - No evidence for a significant non-nitrergic, hyperpolarising factor contribution
to field stimulation-induced relaxation of the mouse anococcygeus.
AB - 1. The aim of the study was to determine whether a nerve-derived hyperpolarizing
factor (NDHF) might contribute to non-adrenergic, non-cholinergic (NANC)
relaxations of the mouse anococcygeus when low concentrations of contractile
agent are used to raise tone and low frequencies of field stimulation applied;
such a non-nitrergic NDHF has been proposed to contribute to NANC relaxations of
the rat anococcygeus and guinea-pig taenia coli. 2. Phenylephrine (0.1-100
microM) produced concentration-related contractions of the mouse isolated
anococcygeus muscle; 0.2 microM phenylephrine (EC26) was used to raise tone in
subsequent experiments. 3. Field stimulation (0.5, 1.0 and 5.0 Hz) produced
frequency-dependent relaxations of phenylephrine-induced tone. In the presence of
the nitric oxide synthase inhibitor L-NG-nitro-arginine (L-NOARG; 100 microM),
the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1
one (ODQ; 5 microM), or a combination of these two drugs, relaxations to field
stimulation were abolished at all frequencies studied. Relaxations to sodium
nitroprusside (0.01-5 microM) were unaffected by L-NOARG but strongly inhibited
by ODQ; neither enzyme inhibitor affected relaxations to 8-Br-cyclic GMP (10
microM). 4. Nifedipine (1 microM) reduced the contractile response to 0.2 microM
phenylephrine by 38%; however, it had no effect on NANC relaxations. 5. It is
concluded that NANC relaxations of the mouse anococcygeus are purely nitrergic
and that there is no significant contribution from a putative NDHF.
PMID- 9647478
TI - Inhibition of the ATP-sensitive potassium channel from mouse pancreatic beta
cells by surfactants.
AB - 1. We have used patch-clamp methods to study the effects of the detergents,
Cremophor, Tween 80 and Triton X100 on the K(ATP) channel in the pancreatic beta
cell from mouse. 2. All three detergents blocked K(ATP) channel activity with the
following order of potency: Tween 80 (Ki< approximately 83 nM)>Triton X100
(Ki=350 nM)>Cremophor. In all cases the block was poorly reversible. 3. Single
channel studies suggested that at low doses, the detergents act as slow blockers
of the K(ATP) channel. 4. Unlike the block produced by tolbutamide, that produced
by detergent was not affected by intracellular Mg2+-nucleotide, diazoxide or
trypsin treatment, nor did it involve an acceleration of rundown or increase in
ATP sensitivity of the chanel. 5. The detergents could block the pore-forming
subunit, Kir6.2deltaC26, which can be expressed independently of SUR1 (the
regulatory subunit of the K(ATP) channel). These data suggest that the detergents
act on Kir6.2 and not SUR1. 6. The detergents had no effect on another member of
the inward rectifier family: Kir1.1a (ROMK1). 7. Voltage-dependent K-currents in
the beta-cell were reversibly blocked by the detergents with a far lower potency
than that found for the K(ATP) channel. 8. Like other insulin secretagogues that
act by blocking the K(ATP) channel, Cremophor elevated intracellular Ca2+ in
single beta-cells to levels that would be expected to elicit insulin secretion.
9. Given the role of the K(ATP) channel in many physiological processes, we
conclude that plasma borne detergent may have pharmacological actions mediated
through blockage of the K(ATP) channel.
PMID- 9647479
TI - Nitric oxide and the haemodynamic profile of endotoxin shock in the conscious
mouse.
AB - 1. The release of cytokines following administration of endotoxin and the
contribution of nitric oxide (NO) to the subsequent haemodynamic profile were
investigated in the conscious mouse. 2. Administration of endotoxin (E. Coli,
026:B6, 12.5 mg kg(-1), i.v.) elevated the concentration of tumour necrosis
factor-alpha (TNF-alpha) in the plasma within 0.5 h, reaching a maximum at 2 h
and returning to control concentrations by 4 h. In addition, the concentration of
interleukin-6 (IL-6) in the plasma was also elevated within 1 h, reaching a
maximum at 3 h and remaining elevated throughout the 12 h of study. 3. Endotoxin
(12.5 mg kg(-1), i.v.) induced the expression of a Ca2+-independent (inducible)
NO synthase in the mouse heart and elevated the concentrations of nitrite and
nitrate in the plasma within 4 h, reaching a maximum at 12 h. This was
accompanied by a progressive fall in blood pressure over the same period. 4. The
vasopressor effect of noradrenaline (0.5-4 microg kg(-1) min(-1), i.v.)
administered as a continuous infusion was significantly attenuated 7 h after
endotoxin (12.5 mg kg(-1), i.v). 5. The NO synthase inhibitor NG-monomethyl-L
arginine HCl (L-NMMA; 1-10 mg kg(-1), i.v. bolus) reversed the fall in blood
pressure when administered 7 h after endotoxin (12.5 mg kg(-1), i.v.). 6. In an
attempt to maintain a constant blood concentration, L-NMMA was administered as a
continuous infusion (10 mg kg(-1) h(-1), i.v.), beginning 4 h after a lower dose
of endotoxin (6 mg kg(-1), i.v.). Such treatment prevented the fall in blood
pressure and the elevation of nitrite and nitrate in the plasma throughout the 18
h of observation. 7. The fall in blood pressure following endotoxin (3 mg kg(-1),
i.v.) was significantly reduced throughout the 18 h of observation in homozygous
mutant mice lacking the inducible NO synthase. 8. In summary, we have developed a
model of endotoxin shock in the conscious mouse in which an overproduction of NO
by the inducible NO synthase is associated with the haemodynamic disturbances.
This model, which exhibits many of the characteristics of septic shock in man,
will enable the study of the pathology of this condition in more detail and aid
the investigation of potential therapeutic agents both as prophylactics and, more
importantly, as treatments.
PMID- 9647480
TI - Effect of rolipram and dibutyryl cyclic AMP on resequestration of cytosolic
calcium in FMLP-activated human neutrophils.
AB - 1. We have investigated the effects of the selective phosphodiesterase (PDE) type
4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated
human neutrophils, as well as on superoxide production by, and release of
elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura
2 spectrofluorimetry in combination with a radiometric procedure that enables
distinction between net efflux and influx of the cation. Superoxide production
and elastase release were measured by lucigenin-enhanced chemiluminescence and a
colorimetric procedure, respectively. 3. Pretreatment of neutrophils with
rolipram did not affect the FMLP-activated release of Ca2+ from intracellular
stores, but was associated with dose-related acceleration of the rate of decline
in fura-2 fluorescence and with decreased efflux, as well as store-operated
influx of 45Ca2+, indicative of enhancement of resequestration of the cation by
the endo-membrane Ca2+-ATPase. 4. Inhibition of superoxide production and
elastase release was observed at concentrations of rolipram which accelerated the
clearance of Ca2+ from the cytosol of FMLP-activated neutrophils. 5. These
effects of rolipram on FMLP-activated Ca2+ fluxes, superoxide generation and
elastase release were mimicked by pretreatment of neutrophils with dibutyryl
cyclic AMP (0.5-4 mM), while theophylline (10-150 microM), a non-specific PDE
inhibitor, as well as the beta2-agonist, salbutamol, were less effective. 6. We
conclude that rolipram deactivates FMLP-stimulated human neutrophils by
enhancement of cyclic AMP-dependent resequestration of cytosolic Ca2+.
PMID- 9647481
TI - Characterization of Ro 04-6790 and Ro 63-0563: potent and selective antagonists
at human and rat 5-HT6 receptors.
AB - 1. This study describes the in vitro characterization of two potent and selective
5-HT6 receptor antagonists at the rat and human recombinant 5-HT6 receptor. 2. In
binding assays with [3H]-LSD, 4-amino-N-(2,6 bis-methylamino-pyrimidin-4-yl)
benzene sulphonamide (Ro 04-6790) and 4-amino-N-(2,6 bis-methylamino-pyridin-4
yl)-benzene sulphonamide (Ro 63-0563) had mean pKi values +/-s.e.mean at the rat
5-HT6 receptor of 7.35+/-0.04 and 7.83+/-0.01, respectively and pKi values at the
human 5-HT6 receptor of 7.26+/-0.06 and 7.91+/-0.02, respectively. 3 .Both
compounds were found to be over 100 fold selective for the 5-HT6 receptor
compared to 23 (Ro 04-6790) and 69 (Ro 63-0563) other receptor binding sites. 4.
In functional studies, neither compound had any significant effect on basal
levels of cyclicAMP accumulation in Hela cells stably expressing the human 5-HT6
receptor, suggesting that the compounds are neither agonists nor inverse agonists
at the 5-HT6 receptor. However, both Ro 04-6790 and Ro 63-0563 behaved as
competitive antagonists with mean +/-s.e.mean pA2 values of 6.75+/-0.07 and
7.10+/-0.09, respectively. 5. In rats habituated to observation cages, Ro 04-6790
produced a behavioural syndrome similar to that seen following treatment with
antisense oligonucleotides designed to reduce the expression of 5-HT6 receptors.
This behavioural syndrome consisted of stretching, yawning and chewing. 6. Ro 04
6790 and Ro 63-0563 represent valuable pharmacological tools for the
identification of 5-HT6 receptors in natural tissues and the study of their
physiological function.
PMID- 9647482
TI - Effects of the cysteinyl leukotriene receptor antagonists pranlukast and
zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in
vitro.
AB - 1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1)
receptor antagonists, pranlukast and zafirlukast, on 35SO4 labelled mucus output,
in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen
challenge of sensitized animals. Agonists and antagonists were administered
mucosally, except in selected comparative experiments where drugs were
administered both mucosally and serosally to assess the influence of the
epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration
related manner with a maximal increase of 23 fold above controls at 100 microM
and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of
LTD4 did not significantly affect the secretory response compared with mucosal
addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output.
Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4
output in a concentration-dependent fashion, with maximal inhibitions of 83% at
10 microM pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3
microM for pranlukast and 0.6 microM for zafirlukast. Combined mucosal and
serosal administration of the antagonists (5 microM each) gave degrees of
inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those
of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward
shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did
not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1)
challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused
a concentration-related increase in 35SO4 output with a maximal increase of 20
fold above vehicle controls at 200 microg ml(-1). The combination of the
antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin
induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100
microM) nor mucosal-serosal (100 microM) histamine had any significant effect on
35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly
suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by
70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of
sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and
this effect is inhibited by the CysLT1 receptor antagonists pranlukast and
zafirlukast. These antagonists may be beneficial in the treatment of allergic
airway diseases in which mucus hypersecretion is a clinical symptom, for example
asthma and allergic rhinitis.
PMID- 9647483
TI - Effects of the 5-lipoxygenase activating protein inhibitor MK886 on voltage-gated
and Ca2+-activated K+ currents in rat arterial myocytes.
AB - 1. The effects on the voltage-gated (IK) and Ca2+ activated (I(K,Ca)) K+ currents
in rat arterial myocytes of the 5-lipoxygenase activating protein (FLAP)
inhibitor MK886, and its inactive analogue L583,916 were evaluated. 2. In rat
pulmonary arterial myocytes (RPAMs), MK886 caused a concentration-dependent
reduction of the IK, with little obvious change in the kinetics of the current.
Half maximal current block was observed at 75 nM MK886. 3. MK886 application led
to a concentration-dependent increase in the amplitude of the TEA-sensitive
I(K,Ca) current and single channel activity in RPAMs in whole cell and inside-out
configurations, respectively. The threshold concentration for this effect was
approximately 300 nM and a maximal 4-5 fold increase was observed at 10 microM
MK886. MK886 also increased I(K,Ca) in rat mesenteric arterial myocytes (RMAMs).
4. L538,916, an analogue of MK886 which does not block FLAP, had no effect on
either IK or I(K,Ca) at a concentration of 10 microM. 5. Leukotriene C4 (100 nM)
had no effect on either IK or I(K,Ca) in RPAMs. MK886 produced its usual increase
in I(K,Ca) and also blocked IK, in the presence of leukotriene C4. Similarly,
leukotriene E4 (100 nM) did not alter the amplitude of IK. Also, the nonselective
leukotriene receptor antagonist ICI 198,615 (3 microM) did not affect IK in
RPAMs, and did not affect the response to MK886. 6. Arachidonic acid (10 microM)
enhanced I(K,Ca) in both RPAMs and RMAMs. 7. The results show that MK886 markedly
affects both IK and I(K,Ca) in a manner similar to that of arachidonic acid and
independent of the endogenous production of leukotrienes. It is therefore
possible that MK886, which is thought to compete with arachidonic acid for its
binding to FLAP, may similarly occupy arachidonic acid binding sites on these K+
channels, and mimic its effects. Alternatively, MK886 might act via non-selective
effects on other arachidonic acid metabolites which could modify K+ channel
function.
PMID- 9647484
TI - T-type and L-type calcium channel blockers exert opposite effects on renin
secretion and renin gene expression in conscious rats.
AB - 1. This study aimed to investigate and to compare the effects of pharmacological
T-type calcium channel and of L-type calcium channel blockade on the renin
system. To this end, male healthy Sprague-Dawley rats were treated with the T
channel blocker mibefradil or with the L-channel blocker amlodipine at doses of 5
mg kg(-1), 15 mg kg(-1) and 45 mg kg(-1) per day for four days and their effects
on plasma renin activity (PRA) and kidney renin mRNA levels were determined. 2.
Whilst amlodipine lowered basal systolic blood pressure at 5 mg kg(-1),
mibefradil had no effect on basal blood pressure in the whole dose range
examined. Amlodipine dose-dependently induced up to 7 fold elevation of PRA and
renin mRNA levels. Mibefradil significantly lowered PRA and renin mRNA levels at
5 mg kg(-1) and moderately increased both parameters at a dose of 45 mg kg(-1),
when PRA and renin mRNA levels were increased by 100% and 30%, respectively. In
primary cultures of renal juxtaglomerular cells neither amlodipine nor mibefradil
(0.1-10 microM) changed renin secretion. 3. In rats unilateral renal artery clips
(2K-1C) mibefradil and amlodipine at doses of 15 mg kg(-1) day(-1) were equally
effective in lowering blood pressure. In contrast mibefradil (5 mg kg(-1) and 15
mg kg(-1) day(-1)) significantly attenuated the rise of PRA and renin mRNA
levels, whilst amlodipine (15 mg kg(-1)) additionally elevated the rise of PRA
and renin mRNA levels in response to renal artery clipping. 4. These findings
suggest that T-type calcium channel blockers can inhibit renin secretion and
renin gene expression in vivo, whilst L-type calcium channel blockers act as
stimulators of the renin system. Since the inhibitory effect of T-type
antagonists is apparent in vivo but not in vitro, one may infer that the effect
on the renin system is indirect rather than directly mediated at the level of
renal juxtaglomerular cells.
PMID- 9647485
TI - Effects of inhibitors of the activity of cyclo-oxygenase-2 on the hypotension and
multiple organ dysfunction caused by endotoxin: a comparison with dexamethasone.
AB - 1. Endotoxaemia is associated with the expression of the inducible isoform of
cyclo-oxygenase, cyclo-oxygenase-2 (COX-2), and an overproduction of arachidonic
acid (AA) metabolites. The role of the AA metabolites generated by COX-2 in the
circulatory failure and multiple organ dysfunction caused by endotoxin is
unclear. Dexamethasone prevents the expression of COX-2 and exerts beneficial
effects in animal models of shock. 2. Here we compare the effects of two
inhibitors of COX-2 activity, namely NS-398 (5 mg kg(-1), i.p., n=7) and SC-58635
(3 mg kg(-1), i.p., n=9) with those of dexamethasone (3 mg kg(-1), i.p., n=9) on
the circulatory failure and organ dysfunction caused by lipopolysaccharide (LPS,
E. coli, 6 mg kg(-1), i.v., n=11) in the rat. 3. Endotoxaemia for 6 h caused
hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury
and an increase in the plasma levels of 6-keto-PGF1alpha (indicator of the
induction of COX-2) and nitrite/nitrate (indicator of the induction of iNOS). 4.
Pretreatment of rats with dexamethasone attenuated the hypotension, the renal
dysfunction, the hepatocellular and pancreatic injury and the induction of COX-2
and iNOS caused by LPS. In contrast, inhibition of COX-2 activity with SC-58635
or NS-398 neither attenuated the circulatory failure nor the multiple organ
failure caused by endotoxin. 5. Thus, the prevention of the circulatory failure
and the multiple organ injury/dysfunction caused by dexamethasone in the rat is
not due to inhibition of the activity of COX-2. Our results suggest that an
enhanced formation of eicosanoids by COX-2 does not contribute to the development
of organ injury and/or dysfunction in rats with endotoxaemia.
PMID- 9647486
TI - Species differences in the distribution of beta-adrenoceptor subtypes in bladder
smooth muscle.
AB - 1. The beta-adrenoceptor (beta-AR) subtypes mediating relaxation of the rabbit,
rat and canine detrusors were subjected to functional investigation using
selective beta-AR agonists and antagonists. 2. In all three species,
isoprenaline, noradrenaline and adrenaline each produced a concentration
dependent relaxation of the detrusor. The rank order for their relaxing potency
was isoprenaline>adrenaline>noradrenaline in rabbits and rats, but
isoprenaline>noradrenaline>adrenaline in dogs. 3. Dobutamine did not produce
relaxation of the detrusors at concentrations that are selective for beta1-AR.
The selective beta2-AR agonist, procaterol, had a more potent relaxing effect on
rabbit and rat detrusors than on the canine detrusor. CGP-12177A, a selective
beta3-AR agonist, was more effective in the rabbit than in the other two species.
On the other hand, the relaxing effect of another beta3-AR agonist, CL316243, was
more pronounced in dogs and rats than in rabbits. 4. CGP-20712A (10(-9) to 10(-7)
M), a selective beta1-AR antagonist, caused a slight rightward shift of the
concentration-relaxation response curve for isoprenaline in the canine detrusor
(pA2 9.41), but not in the rabbit and rat detrusors. ICI-118,551, a selective
beta2-AR antagonist, antagonized the isoprenaline-induced relaxation in rabbits
(pA2 9.45) and rats (pA2 9.05), but not in dogs. Bupranolol, a non-selective beta
AR antagonist, caused a rightward shift of the concentration-relaxation curve for
isoprenaline in the rabbit (pA2 9.32) and rat (pA2 8.98). However, higher
concentrations (3 x 10(-8) to 10(-5) M) were needed to induce a rightward shift
of the curve for isoprenaline in the dog (pA2 8.19) than in the other two
species. 5. We have confirmed that the distribution of beta-AR subtypes in the
detrusor muscle varies significantly from species to species and we provide here
the first evidence of the presence of beta3-AR in the detrusor. It is suggested
that the relaxation induced by adrenoceptor agonists in urinary bladder smooth
muscle may be mediated mainly via beta2-AR in rabbits, via both beta2- and beta3
AR in rats, but mainly via beta3-AR in dogs.
PMID- 9647487
TI - Effects of kappa-opioid receptor stimulation in the heart and the involvement of
protein kinase C.
AB - 1. The role of protein kinase C (PKC) in mediating the action of kappa-receptor
stimulation on intracellular Ca2+ and cyclic AMP production was determined by
studying the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]
cyclohexyl) benzeneacetamide methanesulphonate (U50,488H), a selective kappa
receptor agonist, and phorbol 12-myristate 13-acetate (PMA), a PKC agonist, on
the electrically-induced [Ca2+]i transient and forskolin-stimulated cyclic AMP
accumulation in the presence and absence of a PKC antagonist, staurosporine or
chelerythrine, in the single rat ventricular myocyte. 2. U50,488H at 2.5-40
microM decreased both the electrically-induced [Ca2+]i transient and forskolin
stimulated cyclic AMP accumulation dose-dependently, effects which PMA mimicked.
The effects of the kappa-agonist, that were blocked by a selective kappa
antagonist, nor-binaltorphimine, were significantly antagonized by the PKC
antagonists, staurosporine and/or chelerythrine. The results indicate that PKC
mediates the actions of kappa-receptor stimulation. 3. To determine whether the
action of PKC was at the sarcoplasmic reticulum (SR) or not, the [Ca2+]i
transient induced by caffeine, that depletes the SR of Ca2+, was used as an
indicator of Ca2+ content in the SR. The caffeine-induced [Ca2+]i transient was
significantly reduced by U50,488H at 20 microM. This effect of U50,488H on
caffeine-induced [Ca2+]i transient was significantly attenuated by 1 microM
chelerythrine, indicating that the action of PKC involves mobilization of Ca2+
from the SR. When the increase in IP3 production in response to K-receptor
stimulation with U50,488H in the ventricular myocyte was determined, the effect
of U50,488H was the same in the presence and absence of staurosporine, suggesting
that the effect of PKC activation subsequent to kappa-receptor stimulation does
not involve IP3. The observations suggest that PKC may act directly at the SR. 4.
In conclusion, the present study has provided evidence for the first time that
PKC may be involved in the action of kappa-receptor stimulation on Ca2+ in the SR
and cyclic AMP production, both of which play an essential role in Ca2+
homeostasis in the heart.
PMID- 9647488
TI - Selectivity of action of 8-alkylamino analogues of N6-cyclopentyladenosine in
vivo: haemodynamic versus anti-lipolytic responses in rats.
AB - 1. A1 adenosine receptor agonists with reduced intrinsic activity may be
therapeutically useful as result of an increased selectivity of action. In this
study the tissue selectivity of three 8-alkylamino substituted analogues of N6
cyclopentyladenosine (CPA) was investigated for haemodynamic and anti-lipolytic
effects using an integrated pharmacokinetic-pharmacodynamic approach. 2.
Chronically instrumented male Wistar rats received intravenous infusions of 4.0
mg kg(-1) 8-methylaminoCPA (8MCPA), 12.0 mg kg(-1) 8-ethylaminoCPA (8ECPA), 20.0
mg kg(-1) 8-butylaminoCPA (8BCPA) or vehicle during 15 min. During
experimentation, serial arterial blood samples were drawn for the determination
of agonist concentrations and plasma non-esterified fatty acid (NEFA) levels.
Blood pressure and heart rate were monitored continuously. In addition to the CPA
analogues, each rat received a rapid bolus infusion of CPA to determine the
maximal effects of the full agonist. 3. The concentration-time profiles of the
CPA analogues could be described by a bi-exponential function. Values for
clearance, volume of distribution at steady state and elimination half-life were
44+/-5, 48+/-6 and 39+/-2 ml min(-1) kg(-1), 0.97+/-0.09, 0.84+/-0.10 and 1.05+/
0.07 1 kg(-1) and 25+/-2, 28+/-2 and 40+/-2 min for 8MCPA, 8ECPA and 8BCPA,
respectively (mean+/-s.e.mean, n=6-8). 4. Different models were used to derive
the concentration-effect relationships for heart rate and NEFA, yielding
estimates of potency (EC50) and intrinsic activity (Emax) for both effects of the
compounds in vivo. On heart rate the compounds acted as partial agonists, with
Emax values of -173+/-14, -131+/-11 and -71+/-6 beats min(-1) for 8MCPA, 8ECPA
and 8BCPA, respectively. These Emax values were significantly lower than the
maximal effect of CPA (-208+/-8 beats min(-1)). With regard to the anti-lipolytic
effect all three compounds were full agonists and lowered NEFA levels to the same
extent as CPA (69%). The estimated Emax values were 63+/-5, 63+/-4 and 68+/-2%,
respectively. 5. Furthermore, the compounds were more potent in causing anti
lipolytic than cardiovascular effects. The EC50 values for the NEFA and heart
rate lowering effects were 37+/-15, 68+/-22 and 659+/-108 ng ml(-1) and 164+/-22,
341+/-76 and 975+/-190 ng ml(-1) for 8MCPA, 8ECPA and 8BCPA, respectively (mean+/
s.e.mean, n=6-8). 6. This study demonstrates that partial agonists for the A1
adenosine receptor have increased selectivity of action in vivo. The 8-alkylamino
analogues of CPA may be useful anti-lipolytics with less pronounced haemodynamic
side effects.
PMID- 9647489
TI - Carbamylated proteins and peptides in health and in uremia.
PMID- 9647490
TI - Asymptomatic childhood hypertension.
PMID- 9647491
TI - Secondary hyperparathyroidism in severe chronic renal failure is corrected by
very-low dietary phosphate intake and calcium carbonate supplementation.
AB - The main purpose of our study was to verify the effect of a very-low-protein, low
phosphorus diet, supplemented with essential amino acids and keto analogues and
with calcium carbonate, on circulating levels of intact parathyroid hormone (i
PTH) in severe chronic renal failure patients with secondary hyperparathyroidism,
not treated with any vitamin D preparation. To this aim, we shifted 21 chronic
uremics (12 males, 9 females; age 56 +/- 13 years) with serum creatinine >6.5
mg/dl and i-PTH >150 pg/ml, from a standard low-protein diet (0.6 g/kg/day
approximately) to a very-low-protein (0.3 g/kg/day), very-low-phosphorus (5
mg/kg/day) diet supplemented with a mixture of essential amino acids and calcium
keto analogues (Ketodiet), calcium carbonate (2-4 g/day), iron, and vitamin B12
preparations. The energy supply of both diets was 30-35 kcal/kg/day. Exclusion
criteria were a poor compliance with dietary or supplement prescriptions or signs
of autonomic hyperparathyroidism. After 4 +/- 2 months of Ketodiet, the i-PTH
serum levels decreased by 49% as a mean (from 441 +/- 233 to 225 +/- 161 pg/ml, p
< 0.001); serum phosphorus and alkaline phosphatase decreased, whereas serum
calcium increased. The great reduction of serum and urinary urea demonstrated a
good compliance with Ketodiet, and no sign of protein malnutrition was observed.
These findings confirm that even in severe chronic uremic patients dietary
phosphorus restriction and calcium carbonate supplementation lower i-PTH serum
levels. This is one of the goals of the dietary treatment that can be safely
achieved, provided good compliance both with the dietary prescriptions and with
adequate energy and supplement intakes.
PMID- 9647492
TI - End-stage renal disease following polycythemia vera: in vitro and in vivo
response of erythroid progenitors to erythropoietin and effects of sera on normal
erythropoiesis.
AB - We investigated the in vitro erythroid progenitor growth and the effects of sera
on normal-marrow CFU-E (colony-forming units - erythroid) growth in 2 patients
with renal failure on regular hemodialysis following a prior history of
polycythemia vera (PV). PV was diagnosed 3 and 11 years, respectively, before the
development of terminal renal failure. One of the patients had entered a spent
phase of PV as characterized by diffuse extensive myelofibrosis and anemia; the
other also had mild myelofibrosis. The serum erythropoietin (EPO) levels were low
or normal on serial measurements by radioimmunoassay. There was no correlation
between the hematocrit values and serum EPO levels. EPO-independent erythroid
colonies were present in the cultures of bone marrow and peripheral blood cells
from both patients after renal failure in the anemic state. With the addition of
various concentrations of EPO, the number of erythroid colonies increased as the
concentrations of EPO increased which was in accordance with the clinical
observation that 1 patient with postpolycythemic myeloid metaplasia partially
responded to recombinant human EPO therapy. In the EPO-dependent CFU-E assay,
normal-marrow CFU-E numbers supported by 10% of the patient sera were less than
those by normal sera. In the absence of EPO in cultures, no erythropoietic
activity was found in the patients' sera. Our study on uremic patients with
underlying PV showed that the biologic characteristics of autonomous erythroid
progenitor growth for PV persisted during the spent phase and after the
development of terminal renal failure with anemia. The erythroid progenitors
responded to EPO both in vitro and in vivo. Their sera exhibited an inhibiting
effect on the growth of normal-marrow erythroid progenitors.
PMID- 9647493
TI - Long-term enalapril therapy in patients with chronic renal failure on a low
protein diet. A prospective randomized comparison with metoprolol.
AB - The effect of enalapril (5-10 mg/day) on the progression of chronic renal failure
(CRF) was compared with that of metoprolol (40-120 mg/day) in 28 patients for 24
months in a prospective study. Throughout the study, there was no significant
difference between the 2 groups in protein intake and urinary sodium excretion.
But there was a significant difference between the 2 groups in diastolic and mean
arterial blood pressure at 6 months. In the serum creatinine level, there was a
significant difference between the 2 groups at 6, 12, 18, and 24 months. In
creatinine clearance, there was a significant difference between the 2 groups at
24 months. In addition, the progression of CRF was significantly faster in the
metoprolol group than the enalapril group as estimated from the slope of
creatinine clearance (p < 0.05) and the slope of glomerular filtration rate (p <
0.0005). In urinary protein excretion, there was a significant difference between
the 2 groups at 6 and 18 months (p < 0.05). These findings indicate that
enalapril has a suppressive effect on the progression of CRF and also has an
antiproteinuric effect by a mechanism independent of its antihypertensive effect.
PMID- 9647494
TI - Direct method for the measurement of low-density lipoprotein cholesterol levels
in patients with chronic renal disease: a comparative assessment.
AB - BACKGROUND/AIM: This study was performed to comparatively evaluate the results
obtained for low-density lipoprotein (LDL) cholesterol concentrations by either a
newly described direct method or the Friedewald equation in subjects with and
without chronic renal disease. METHODS: Fasting plasma was obtained from a total
of 169 subjects, 105 with normal renal function (including 53 hyperlipidaemic)
and 64 with chronic renal disease (nephrotic syndrome and/or chronic renal
failure; including 40 hyperlipidaemic patients), and analyzed for LDL cholesterol
using the Friedewald equation and a direct LDL assay method. RESULTS: The
Friedewald equation and the direct LDL cholesterol assay correlated well with
each other (r = 0.79-0.90 in all subjects with plasma triglyceride, TG, levels
greater than or less than 4.0 mmol/l and with and without chronic renal disease
and/or hyperlipidaemia, all p < 0.0001). The values for LDL cholesterol, however,
tended to be higher with the direct measurement. This mean difference was trivial
in hyperlipidaemic subjects with (8.5%) and without (7.1%) normal renal function
(both p < 0.05), but could be clinically significant in those with TG >4.0 mmol/l
(mean difference 18%, p < 0.001). Indeed, bias plots confirmed this observation
of wider negative bias for Friedewald estimation in these moderately
hypertriglyceridaemic subjects. CONCLUSION: For most routine laboratories the
options immediately available for assessment of lipid levels are the Friedewald
equation or the direct measurement. The Friedewald equation and the direct assay
method for LDL cholesterol are about equally good for assessment of the LDL
status in patients with chronic renal disease and plasma TG <4.0 mmol/l. Where
there are restraints on laboratory budgets, it would appear appropriate that the
more expensive direct assay method be restricted to cases in whom plasma TG >4.0
mmol/l or to patients who, for whatever reason, are unable to produce fasting
samples.
PMID- 9647495
TI - Effects of extracorporeal shock wave lithotripsy on renal function in patients
with kidney stone disease.
AB - The effects of extracorporeal shock wave lithotripsy on glomerular and tubular
renal functions were determined by serum beta2-microglobulin (Sbeta2m) and
urinary beta2-microglobulin (Ubeta2m) estimations in patients with
nephrolithiasis. Unilateral treatment was performed in all patients. Urinary and
serum creatinine levels were determined according to the method of Yatzidis.
Sbeta2m and Ubeta2m were measured by radioimmunoassay the day before ESWL, on the
day of ESWL, and then 1, 2, 5, 7, 8, 9, 14, and 28 days after treatment.
Creatinine clearance, hourly urinary beta2m excretion (Ubeta2m/h), and tubular
reabsorption of beta2m (TRbeta2m) were calculated. After lithotripsy, significant
increases in Ubeta2m, Ubeta2m/h, and TRbeta2m were found (p < 0.001), whereas
Sbeta2m, serum creatinine, and creatinine clearance values remained unchanged.
Ubeta2m, Ubeta2m/h, and TRbeta2m reached their pretreatment values within 7-9
days after ESWL. We concluded that ESWL does not affect the glomerular filtration
rate; however, it leads to a transient proximal tubular dysfunction.
PMID- 9647496
TI - Urinary excretion of Tamm-Horsfall protein and epidermal growth factor in chronic
nephropathy.
AB - Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both
synthesized by tubular cells in the distal part of the nephron and excreted with
the urine. The present study examines the urinary excretion rates of the two
peptides in relation to functional tubular markers in patients with chronic
nephropathy. Four groups of patients with moderate to severely reduced renal
function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n =
11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n =
8). The renal function was evaluated by glomerular filtration rate (GFR) as an
indicator for the general renal function, lithium clearance (C(Li)) as an
indicator for proximal tubular function, and absolute distal reabsorption of
sodium (ADR(Na)) as an indicator for distal tubular function. The excretion rate
of EGF was rather closely correlated with GFR, C(Li) and ADR(Na) (Spearman
coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations
between the excretion rate of THP and GFR, C(Li) and ADR(Na) were weaker
(Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR
had been accounted for by multiple variance analyses, the excretion rates of the
two peptides were still associated with ADR(Na) but not with C(Li). In
conclusion, the urinary excretion rates of especially EGF but also those of THP
were correlated with renal function and distal tubular reabsorption of sodium in
patients with chronic nephropathy.
PMID- 9647497
TI - Comparison of a vegetable-based (soya) and an animal-based low-protein diet in
predialysis chronic renal failure patients.
AB - There is some experimental evidence to suggest that progression of chronic renal
failure (CRF) is slower on diets based on soya protein than on diets based on
animal protein. We have compared the effect of a soya-based vegetarian low
protein diet (VPD) and an animal-based low-protein diet (APD) in 15 patients with
CRF. 15 patients with CRF (51Cr-EDTA-measured glomerular filtration rate 15-50
ml/min/1.73 m2) were studied. In a randomized crossover trial, the patients were
given each diet (each containing 0.75 g protein and 32 kcal per kilogram body
weight) for a 6-month period. Nine patients completed the trial, 2 others dropped
out because they could not tolerate the VPD, 3 because of unrelated medical
complications, and 1 for technical reasons. The caloric intake was higher and the
protein, phosphate and essential amino acid intake lower on the VPD than on the
APD. The compliance with the suggested caloric intake was better with the VPD
than with the APD (97 vs. 88% of recommended intake), as was the compliance with
the suggested protein intake (94 vs. 112% of recommended intake) and with the
suggested phosphate intake (102 vs. 116%). The mean glomerular filtration rate,
as judged by 51Cr-EDTA, was similar after 6 months on each diet and remained
unchanged throughout the entire year of the study. The rate of fall of glomerular
filtration, as measured by the slope of 1/serum creatinine was slowed by 73%
during the 1-year study period as compared with the prestudy period. Nutritional
status (as measured by body mass index, midarm circumference, and lean body mass
and percent body fat), serum transferrin, cholesterol and albumin, and total
lymphocyte count were similar on the two diets. The serum albumin level on both
diets, however, was significantly higher on the two diets than during the prediet
period. Blood urea nitrogen, urine urea nitrogen, protein catabolic rate, and 24
hour urine creatinine and phosphate were lower on the VPD than on the APD. The 24
hour protein excretion was similar on the two diets. The two low-protein diets
resulted in a slowing in the progression of CRF. A VPD is well tolerated in CRF
and is associated with lower protein and phosphate intakes and a higher caloric
intake than an APD and may, therefore, be used as a safe alternative or partial
substitute for the usual APD in CRF.
PMID- 9647498
TI - Antioxidant defense potential of rabbit renal tissues after ESWL: protective
effects of antioxidant vitamins.
AB - Antioxidant defense potential, malondialdehyde (MDA) levels, and relative
hydroxyl radical (OH.) concentrations were measured in order to establish the
effects of extracorporeal shock wave lithotripsy (ESWL) on free radical
production and antioxidant defense potential of the rabbit kidney tissues.
Electron microscopic examination was also performed to observe ultrastructural
changes. The antioxidant defense potential of the ESWL-treated tissues was found
to be reduced, and the MDA levels increased as compared with controls. Vitamin
(vitamin E plus C combination) pretreatment ameliorated antioxidant defense
potential in part, prevented increases in MDA levels in the ESWL-treated tissues,
and increased the antioxidant defense potential in the control kidney tissues.
After ESWL, a significant amount of OH. radical was measured in the affected
tissue. This revealed the source of oxidant stress and peroxidation reactions in
the ESWL-treated kidney tissue. Vitamin pretreatment caused significant reduction
in the OH. radical concentration. In the electron microscopic investigation, some
significant subcellular changes, such as endothelial injury, loss of foot
processes, damage of glomerular basal membrane, etc., were observed in the ESWL
treated renal tissue slices. Vitamin pretreatment to a great extent prevented
formation of these subcellular changes. Our results suggest that the antioxidant
capacity of the kidney tissue was reduced after ESWL treatment and that the
tissue was exposed to oxidant stress. Vitamin pretreatment exerted significant
protection against the radical damage.
PMID- 9647499
TI - Apoptosis and expression of Bax protein and Fas antigen in glomeruli of a remnant
kidney model.
AB - The role of apoptosis in glomerular cell depletion associated with a decrease in
renal function is still controversial. To examine the involvement of apoptosis in
renal disease, the occurrence of apoptosis during the progression of renal
insufficiency as well as the expression of Bax protein and Fas antigen that are
related to the apoptosis were investigated using five-sixths nephrectomized rats,
one of the progressive renal disease models. Serum creatinine was significantly
elevated to a level approximately five-fold higher than that in the sham-operated
group on day 1 after the five-sixths nephrectomy and then maintained at a level
approximately two- to three-fold higher until day 56 and then elevated further to
a level eight-fold higher on day 96 after nephrectomy as compared with the sham
operated group. The total number of glomerular cells was significantly increased
from day 7 to day 56 after nephrectomy and then returned to the level of the sham
operated group by day 96. The number of PCNA-positive cells (a marker of
proliferating cells) in the glomeruli was significantly increased from day 7 to
day 28 after nephrectomy; the highest level was observed on day 7, and the
numbers then decreased gradually. Apoptotic cells, which were represented by
TUNEL-positive cells, as well as apoptotic bodies were persistently increased
with time after nephrectomy in the glomeruli of nephrectomized rats; apoptotic
cells could hardly be observed in the sham-operated group. Therefore, glomerular
cell proliferation appeared to begin immediately after nephrectomy and to
continue until day 28 at a level high enough to overcome the decrease in the
number of glomerular cells due to apoptosis, since the total number of glomerular
cells was apparently high until day 56. On day 96, the decrease in the number of
glomerular cells probably becomes predominant over cell proliferation, since
apoptosis continuously increased with time after nephrectomy. The events on day
96 may be associated with the severely decreased renal function which was
represented by the explosive increase in the serum creatinine level on the same
day. The number of Fas antigen positive glomerular cells was increased from day 1
after nephrectomy and reached a plateau on day 21. The number of Bax protein
positive glomerular cells was generally increased with time after nephrectomy,
but the number was slightly decreased on day 21. The theory that the expression
of Bax protein is correlated with apoptosis appears to fit the case of
progressive renal disease. These results suggest that apoptosis is involved in
the cell depletion of progressive renal insufficiency.
PMID- 9647500
TI - Acute volume expansion and salt-loading studies in rats. The role of atrial
natriuretic peptide and catecholamines.
AB - Differences have been postulated for the mechanism of natriuresis due to atrial
natriuretic peptide (ANP), salt loading with high salt diet (HS) and acute volume
expansion (AcVE), in particular between AcVE and ANP based on the observed
synergism between the two. Therefore the effects of and the interaction between
the three were investigated in rats. ANP and AcVE produced the same natriuresis
in HS as in normal salt (NS) rats and, in both, the actions of ANP and AcVe were
significantly additive showing similarity in mechanisms. Synergism [(AcVE + ANP)
AcVE] was, however, present only in the NS rats. Proximal tubular sodium
transport was the same with AcVE and ANP+AcVE suggesting that synergism is a
property of more distal nephron segments. In conscious HS rats, plasma ANP was
significantly less but natriuresis was higher than in NS rats. ANP therefore
probably has some causative role in the natriuresis of AcVE but none in that of
HS loading. Urinary dopamine was significantly increased by HS and further
increased by AcVE in both NS and HS rats, the relationship between dopamine and
natriuresis being significantly positive (r2 = 0.328) reaching equivalent levels
in both NS and HS rats. Systemic benserazide prevented the increase in urinary
dopamine but only attenuated the natriuresis of AcVE. We conclude that HS does
not potentiate the natriuresis of AcVE or ANP, synergism between AcVE and ANP is
not a proximal tubule event and dopamine accounts for significant natriuresis of
VE in addition to other natriuretic factors.
PMID- 9647501
TI - High-protein diet or unilateral nephrectomy induces a humoral factor(s) that
enhances mesangial cell proliferation in culture.
AB - BACKGROUND: A high-protein diet is one of the maneuvers which produce hypertrophy
of kidney mass. The underlying mechanism(s) has not been elucidated. In the
present study, we investigated the possibility that a humoral factor may be
involved. METHODS: Twenty-eight 3-week-old Charles River rats were studied.
Fourteen underwent right nephrectomy and 14 sham operation. Each of these groups
was divided into two equal subgroups (n = 7 in each): one maintained on a regular
diet (20% protein) and the other on a high-protein diet (60% protein) for 7 days.
Following this period the animals were sacrificed. Sera from the animals were
added to mesangial cell cultures from kidneys of intact 3-week-old rats, and the
thymidine incorporation was assessed. RESULTS: The parameters of kidney mass
indicated that the high-protein diet indeed produced kidney hypertrophy. Sera
from the sham-nephrectomized animals fed a high-protein diet produced a
significantly greater proliferative effect on mesangial cells in culture than
sera from the respective animals on a normal-protein diet. Sera from either
nephrectomized group or from the high-protein sham-operated group all had similar
magnitudes of enhancement of mesangial cell proliferation. CONCLUSION: We
conclude that the renal hypertrophy produced by a high-protein diet is mediated,
at least in part, by a humoral factor(s).
PMID- 9647502
TI - Recovery of damaged glomerular capillary network with endothelial cell apoptosis
in experimental proliferative glomerulonephritis.
AB - Capillary repair can occur in damaged glomeruli in recovery models of
glomerulonephritis (GN). In order to clarify whether capillary repair is an
essential component in glomerular recovery from GN, we have examined the
development of the capillary repair after inflammatory injury in both the
repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN.
Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody
administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning
developed in damaged glomeruli by day 3, with reduction of endothelial
cellularity. Thereafter, histological proliferative GN developed between day 5
and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5,
and the number of glomerular endothelial cells increased and exceeded the level
of control values on day 7. Angiogenic glomerular capillary repair occurred
through the process of not only capillary regeneration from remaining endothelial
cells in capillary aneurysmal lesions but also new capillary growth derived from
the glomerular vascular poles by day 7. The number of glomerular capillary lumina
also increased to the level of controls by week 3. Subsequently, mesangial
proliferative GN resolved, and most of the glomeruli recovered to their normal
structure with the reconstruction of the capillary network by weeks 4-6. In the
glomerular capillary repair, significant apoptosis of glomerular endothelial
cells was present during the period of mild endothelial cell hypercellularity
between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cells/glomerular
cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM; p < 0.05. In Thy-1 GN,
most of the damaged glomeruli recovered with angiogenic capillary repair.
However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli
with an incomplete repair of glomerular capillaries. Therefore, it is concluded
that following the destruction of the glomerular capillary network in GN,
angiogenic capillary repair plays an essential role in the recovery of damaged
glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in
damaged glomeruli. Glomerular capillary repair occurs through the process of
capillary regeneration from remaining endothelial cells as well as new glomerular
capillary growth from the glomerular vascular poles. In glomerular capillary
repair, apoptosis is necessary in regulating the number of intrinsic endothelial
cells.
PMID- 9647503
TI - Primary hyperparathyroidism in a patient with systemic lupus erythematosus
antiphospholipid syndrome.
PMID- 9647504
TI - In vitro production of interleukin-1, interleukin-6 and tumor necrosis factor
alpha by different blood cells in patients on intermittent peritoneal dialysis.
PMID- 9647505
TI - A case of amyloidal anal polyp in long-term hemodialysis.
PMID- 9647506
TI - IgA nephropathy: to treat or not to treat?
PMID- 9647507
TI - High prevalence of hepatitis C virus infection in one dialysis center in
Bulgaria.
PMID- 9647508
TI - Exercise training and the progression of chronic renal failure.
PMID- 9647509
TI - Anti-glomerular basement membrane and anti-neutrophil cytoplasm antibody-positive
vasculitis presenting with peripheral neuropathy and acute renal failure.
PMID- 9647510
TI - Gabexate mesilate plus intravenous gammaglobulin treatment in children with
diarrhoea-associated haemolytic uraemic syndrome.
PMID- 9647511
TI - Treatment of chronic hepatitis C with interferon alpha in patients on maintenance
hemodialysis.
PMID- 9647512
TI - Renal functional reserve in asymptomatic carriers of human immunodeficiency
virus.
PMID- 9647513
TI - Fluorosis, osteomalacia and pseudohyperparathyroidism in a patient with renal
failure.
PMID- 9647514
TI - Nephrotic syndrome associated with inflammatory bowel disease treated by
mesalazine.
PMID- 9647515
TI - Alport syndrome in Reunion Island: phenotypic heterogeneity of the recessive
autosomal form.
PMID- 9647516
TI - Rapidly progressive immunotactoid glomerulonephritis and multiple myeloma.
PMID- 9647517
TI - Mediterranean spotted fever with acute renal failure stimulating a relapse in C
ANCA vasculitis.
PMID- 9647519
TI - Association of Gitelman's syndrome and focal glomerulosclerosis.
PMID- 9647518
TI - Is the hepatitis C seroconversion rate higher with dialysis catheters than A-V
fistula.
PMID- 9647520
TI - Prevalence of heparin-induced PF4-heparin antibodies in hemodialysis patients.
PMID- 9647521
TI - Normotensive primary aldosteronism due to adrenocortical carcinoma.
PMID- 9647522
TI - Learning from the past, venous thromboembolism and the pill: an endless saga.
PMID- 9647523
TI - Recommendations on the safety of oral contraceptives are too important for the
regulating agencies alone.
PMID- 9647524
TI - Thromboembolism and the pill: the saga must end.
PMID- 9647525
TI - Incomplete compensation following the ban on third generation oral
contraceptives.
PMID- 9647526
TI - The pill and venous thromboembolism: a disarray of several layers of debate.
PMID- 9647527
TI - Learning from the past: an essential need.
PMID- 9647528
TI - Friendly IVF: the way of the future?
PMID- 9647529
TI - Prenatal testing for late-onset diseases such as mutations in the breast cancer
gene 1 (BRCA1). Just a choice or a step in the wrong direction?
PMID- 9647530
TI - A rational approach to prenatal screening and intervention.
PMID- 9647531
TI - The donation of gametes is possible without paying donors: experience of the
French CECOS Federation. Centre for the cryopreservation of eggs and semen.
PMID- 9647532
TI - Recruitment of gamete donors and payment of expenses.
PMID- 9647533
TI - Development of human primordial follicles to antral stages in SCID/hpg mice
stimulated with follicle stimulating hormone.
AB - In contrast to the many detailed studies of Graafian follicles, the biology of
small follicles in the human ovary is poorly understood and the trigger for
follicular growth initiation remains unknown. No practical model exists to study
preantral follicle growth in the human because of their slow growth rate and lack
of an effective culture system. We therefore tested ovarian xenografts as a new
strategy to study the early stages of ovarian follicular growth in vivo. Mice
homozygous for severe combined immunodeficiency (SCID) and hypogonadism (hpg)
received human ovarian xenografts under their kidney capsules. Follicle growth
was assessed by morphology and proliferating cell nuclear antigen (PCNA)
immunostaining. The grafts were recovered after 11 (short-term) and 17 weeks
(long-term), and serially sectioned. During the last 6 weeks of long-term
grafting, mice were randomized to receive either placebo or 1 IU of purified
follicle stimulating hormone (FSH) s.c. on alternating days. After 11 weeks of
grafting, the most advanced follicles had a maximum of two granulosa cell layers.
In the absence of FSH administration, follicles did not progress beyond the two
layer stage even after 17 weeks of grafting, and the oestradiol levels remained
undetectable. In the FSH-treated long-term grafts, follicles had grown to antral
stages and resulted in oestradiol levels as high as 2070 pmol/l. Growth
initiation indices did not differ between control and FSH-treated grafts. This
study demonstrates that follicles can survive and grow in human ovarian tissue
grafted under the renal capsules of immunodeficient mice for at least 17 weeks,
and indicate that xenograft models are potentially useful for studying human
follicle development. Using this physiological model, we showed that FSH is
required for follicle growth beyond the two-layer stage, although growth
initiation is independent of gonadotrophin stimulation.
PMID- 9647534
TI - The effect of recombinant follicle stimulating hormone (Gonal-F) on endogenous
luteinizing hormone secretion in women.
AB - Parenteral administration of follicle stimulating hormone (FSH) has been shown to
lower luteinizing hormone (LH) concentrations in women undergoing ovulation
induction. This study was designed to explore the physiological mechanism of this
effect. Seven healthy women were recruited into a double-blind placebo-controlled
study. LH secretion, after the administration of variable i.v. boluses (37.5, 75
and 150 IU) of recombinant FSH (Gonal-F), was evaluated. LH was measured at 10
min intervals for 2 h before and 4 h after the FSH/placebo infusion. LH pulse
frequency and amplitude were evaluated and there was no significant difference
between control and trial cycles for each subject. A linear regression analysis
revealed that in the group receiving 150 IU FSH, the mean plasma LH concentration
decreased significantly due to a reduction tonic LH secretion. This could be a
result of the suppression of secretion or an alteration of clearance. This
decrease was not seen in the other dosage groups, revealing that above a dosage
threshold, FSH reduced non-pulsatile LH secretion. Therefore the effect of FSH in
this study exposed the likely presence of two components of LH concentration: an
FSH-sensitive, non-pulsatile tonic secretion and a gonadotrophin-releasing
hormone-stimulated, pulsatile release that is unaffected by FSH. Although an
indirect effect involving ovarian regulation is not excluded, the rapidity of the
effect suggests that FSH acts directly on the pituitary gland.
PMID- 9647535
TI - Human follicle fluid vascular endothelial growth factor concentrations are
correlated with luteinization in spontaneously developing follicles.
AB - Vascular endothelial growth factor (VEGF) is a cytokine that induces
angiogenesis. Angiogenesis is a prominent histologic component of the
luteinization process. Luteinization is also characterized by granulosa cell
progesterone secretion in response to the luteinizing hormone (LH) surge. Local
VEGF production in human pre-ovulatory follicles, induced by LH, was postulated
to be a luteinization mediator in women. To investigate this hypothesis, serum
and fluid from the dominant follicle of 31 healthy regularly cycling multiparous
women undergoing laparoscopic sterilization were obtained. VEGF was measured by
enzyme-linked immunosorbent assay, and LH and progesterone were measured by
radioimmunoassay. Follicle aspiration was performed at a median of 13 days from
the last menstrual period (range 11-17 days). The median pre-ovulatory follicle
diameter was 16 mm (range 11-23 mm). Follicle fluid VEGF concentrations (mean
6900 pg/ml, range 1200-17 100 pg/ml) were correlated positively with follicle
fluid progesterone concentrations (mean 10 176 nmol/l, range 636-66780 nmol/l,
r=0.62, P=0.002). This correlation was even tighter (r=0.87, P < 0.0001) when
only samples from the 22 women in the earliest stages of follicle luteinization
were considered. In these women serum LH concentrations were also correlated with
follicle fluid VEGF concentrations (r=0.51, P=0.02). Our findings demonstrate the
close dynamic relationship between VEGF production and early luteinization in
human follicles during normal non-stimulated cycles.
PMID- 9647536
TI - The use of long- and short-acting forms of gonadotrophin-releasing hormone
analogues in women undergoing oocyte donation.
AB - Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use
of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for
pituitary desensitization may impair the outcome of IVF as compared to classical
short-acting formulations. Whether the negative effects are directed against the
corpus luteum, the endometrium, or both is unknown. However, the presence of high
affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human
endometrium suggests a possible role of these analogues on this target organ,
affecting embryo implantation. In the present study, we tested direct effects of
two different forms of GnRHa on implantation using the ovum donation model.
Patients were prospectively allocated to one of the three study groups: the short
acting form of the analogue leuprolide acetate (group I; n=64), the long-acting
form of the same analogue (group II; n=58), and the long-acting preparation of
the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo
transfer was carried out in group I, whereas 67 were performed in group II and 65
in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because
of bleeding while being on the waiting list for anonymous oocyte donation. The
number of oocytes donated, fertilization rates and embryos replaced in each group
were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6%
respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1
and 17.0%. These data suggest that the use of a long-acting form of GnRHa
provides success rates similar to the short-acting preparations, resulting in
more convenient medication for patients with ovarian function included in ovum
donation programmes.
PMID- 9647537
TI - Leptin concentrations in the follicular phase of spontaneous cycles and cycles
superovulated with follicle stimulating hormone.
AB - It has been reported that oestradiol may play a role in the production of leptin
from adipocytes. To investigate this relationship further, nine normally
ovulating women were studied during two menstrual cycles, i.e. an untreated
spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH)
from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection.
Serum leptin values on cycle day 2 did not differ significantly between the
spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined
gradually and significantly up to day 7 and then increased progressively up to
the day of luteinizing hormone (LH) surge onset, at which point they achieved the
highest values. In the FSH cycles, serum leptin values increased gradually and
significantly up to day 6, remaining stable thereafter, and were in the
midfollicular phase significantly higher than in the spontaneous cycles.
Significant positive correlations were found between mean values of leptin and
mean values of oestradiol during the second half of the follicular phase in the
spontaneous cycles and during the first half in the FSH cycles. A significant
negative correlation was found between these two parameters in the spontaneous
cycles during the first half of the follicular phase. Serum leptin levels were
significantly higher in the midluteal than in the follicular phase in both
cycles. These results demonstrate for the first time significant changes in
leptin values during the follicular phase of the human menstrual cycle and a
significant increase during superovulation induction with FSH. It is suggested
that oestradiol may be involved in the regulation of leptin production in women.
PMID- 9647538
TI - Does withholding gonadotrophin administration prevent severe ovarian
hyperstimulation syndrome?
AB - Withholding gonadotrophin administration (coasting) may prevent severe ovarian
hyperstimulation syndrome (OHSS). To ascertain the effectiveness of this
protection a cohort of 252 consecutive in-vitro fertilization (IVF) or IVF with
intracytoplasmic sperm injection (ICSI) cycles was studied. Twenty women with
exaggerated response were treated with coasting. Despite coasting, four patients
developed severe OHSS requiring hospitalization. Two of these four patients also
required paracentesis. Multiple regression analysis in coasting cycles revealed
severe OHSS was related to youth, number of oocytes retrieved and serum
oestradiol prior to human chorionic gonadotrophin (HCG). Risk of developing
severe OHSS was multifactorial and not necessarily prevented by withholding
gonadotrophin.
PMID- 9647539
TI - Effect of delta-opioid receptor agonist deltorphin on circulating concentrations
of luteinizing hormone and follicle stimulating hormone in healthy fertile women.
AB - There is evidence that endogenous opioid peptides exert an inhibitory effect on
pituitary luteinizing hormone (LH) secretion both in animals and in humans, by
interacting with mu-opioid receptors. However, a role for delta-opioid receptors
in the regulation of gonadotrophin releasing hormone (GnRH) secretion has
recently been suggested. In the present study, we evaluated the effect of the
highly selective delta-opioid receptor agonist deltorphin on the LH and follicle
stimulating hormone (FSH) responses to naloxone in six healthy fertile women
during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7
microg/kg/min for 60 min) did not significantly change the basal serum
concentrations of LH in this group of women. The intravenous (i.v.) bolus
administration of naloxone (15 mg) induced a significant (P < 0.001) increase in
serum LH concentrations (from a mean basal value of 4.24+/-1.10 IU/l to a peak of
13.27+/-1.8 IU/l). The LH response to naloxone was significantly (P < 0.001)
blunted by preinfusion of deltorphin (13.27+/- 1.80 IU/l versus 4.80+/-1.18
IU/l). No significant changes in FSH concentrations were observed during
deltorphin, naloxone or deltorphin plus naloxone administration. These data
indicate that activation of delta-opioid receptors can reduce naloxone-induced LH
release, suggesting a possible role of delta receptors in opioidergic modulation
of LH secretion in women.
PMID- 9647540
TI - Endocytosis and MHC class II expression by human oviductal epithelium according
to stage of the menstrual cycle.
AB - The epithelium is the first barrier against pathogens invading the lumen of the
human oviduct. Its expression of class II major histocompatibility complex (MHC
class II) proteins suggests that it might play a role in antigen presentation
during the local immune response. To study the role of the oviductal epithelium
in antigen processing, its endocytic properties and MHC class II expression were
examined. For assay of endocytosis, fluorescein isothiocyanate-labelled bovine
serum albumin (BSA-FITC) or Escherichia coli (E. coli-FITC) was infused into the
lumen. One-centimetre pieces of oviduct were incubated for 2 h and processed for
fluorescence and confocal microscopy, and transmission electron microscopy.
Incorporation into secretory and ciliated epithelial cells was observed, which
was unrelated to the phase of the menstrual cycle. Small pieces of the organs
were frozen and processed for immunohistochemistry. Most oviducts expressed MHC
class II (HLA.DR) in the epithelium and in some cases this was coincident with
endocytosis, but there was no statistically significant association between this
expression and either endocytotic activity or the phase of the menstrual cycle.
Results demonstrate that the epithelium of the human oviduct exhibits endocytic
properties towards luminal soluble and particle antigens, which is not related
either to MHC class II expression or to the phase of the menstrual cycle.
PMID- 9647541
TI - Reactivity of human trophoblast monoclonal antibodies with marmoset monkey
trophoblast cultures.
AB - The aim of this study was to determine whether cultured trophoblast tissues,
derived from the trophectoderm of marmoset monkey blastocysts, contain homologues
of human trophoblast antigens. This is an essential prerequisite to determine
whether the marmoset may be a suitable model for preclinical testing of a human
antitrophoblast antigen for fertility regulation. Previously evaluated monoclonal
antibodies from the Flinders University laboratory, which reacted with human
trophoblast with a high degree of specificity, were tested for
immunohistochemical reactivity using an immunoperoxidase detection method on both
frozen and paraformaldehyde-fixed sections of the cultured marmoset monkey
trophoblast. All monoclonal antibodies raised against human placenta reacted
positively, when compared to controls, suggesting that human and marmoset
trophoblast cells share common epitopes. The specificity of the monoclonal
antibodies was investigated by determining whether there was cross-reactivity
with other marmoset monkey tissues, including adrenal, spleen, kidney, liver,
muscle, ovary and testis. The specificities of the monoclonal antibodies on these
marmoset tissues were similar to those previously found on the corresponding
human tissues. We have concluded that marmoset monkey trophoblast exhibits
homologues of human trophoblast antigens. The findings also suggest that marmoset
monkeys should be evaluated further as a primate model to test suitable target
antigens for antitrophoblast vaccines that may be useful contragestation agents
in humans.
PMID- 9647542
TI - Circulating antibodies to a conserved epitope of the Chlamydia trachomatis 60 kDa
heat shock protein (hsp60) in infertile couples and its relationship to
antibodies to C.trachomatis surface antigens and the Escherichia coli and human
HSP60.
AB - To evaluate the relationship between immunity to specific regions of the
Chlamydia trachomatis 60 kDa heat shock protein (hsp60), autoimmunity to human
HSP60 and infertility, sera from 50 women and 45 men seen for an infertility
evaluation were tested. Humoral immunity to human HSP60 was detected in 18% of
women and 8.9% of men while antibodies to the Escherichia coli hsp60 were
detected in 12% of women and 4.4% of men. These differences were not
statistically significant. In contrast, antibodies to a synthetic peptide epitope
of the chlamydial hsp60, encompassing amino acids 260-271 (chsp 260-271), were
present in sera from 16 (32%) of the women but in only six (13.3%) of the men
(P=0.03). Antibodies to chsp 260-271 were present in 11 out of 17 (64.7%)
individuals with high titre (>1:160) immunoglobulin (Ig)G antibody to
C.trachomatis surface antigens as opposed to only two out of 15 (13.3%) with low
titre antibody and two out of of 17 (11.8%) with undetectable chlamydial antibody
(P < 0.004). Antibodies to chsp 260-271 were also associated with humoral
immunity to human HSP60. 50% of sera with, as opposed to only 18.6% of sera
without, anti-human HSP60 IgG were positive for antibodies to chsp 260-271
(P=0.03). In contrast, there was no relationship found between immunity to the
E.coli hsp60 and antibodies to human HSP60. Antibodies to chsp 260-271 were more
prevalent in women with at least two spontaneous abortions (eight out of 13,
61.5%) than in women with other infertility diagnoses (six out of 35, 17.1%)
(P=0.004). Thus, immunity to chsp 260-271 is more prevalent in women than in men,
associated with autoimmunity to human HSP60 and may be an immunological marker
for spontaneous abortion.
PMID- 9647543
TI - Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro
fertilization and embryo transfer cycle.
AB - Increased antiphospholipid antibody prevalence has been demonstrated by a number
of recent studies in in-vitro fertilization (IVF) patients but the potential
effects of antiphospholipid antibodies on the different components of the
reproductive process and the consideration of whether to test IVF patients for
antiphospholipid antibodies are controversial. The present study was undertaken
to investigate the possible association between the presence of circulating
antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin
antibodies), among a series of 21 consecutive IVF patients having a clinical
spontaneous abortion after their first embryo transfer. As a control group
(n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after
each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to
the index cycle) was used. One patient (4.8%) in the study group and two women
(4.8%) among controls were seropositive for antiphospholipid antibodies. These
low and similar seropositivity rates found in the two groups studied lead us to
conclude that antiphospholipid antibodies testing in IVF patients should be
considered only in those women having repeated failures of implantation/clinical
abortion after embryo transfer but not in an infertile general population
reaching an IVF programme.
PMID- 9647544
TI - Fragile X premutation screening in women with premature ovarian failure.
AB - We have screened 132 women with premature ovarian failure for fragile X (FRAXA)
premutations. Three out of 23 (13%) pedigrees with the familial premature ovarian
failure and 3/106 (3%) of women with the sporadic form of premature ovarian
failure have FRAXA premutations compared with an expected prevalence of 1:590
(P=0.02). The mechanism of the association between FRAXA premutations and
premature ovarian failure is unknown but as a genetic marker, FRAXA screening
will be particularly valuable in predicting premature ovarian failure in some
pedigrees and in the identification of families at risk of transmitting fragile X
syndrome.
PMID- 9647545
TI - Hysteroscopic septum resection in patients with recurrent abortions or
infertility.
AB - Fifty-seven patients who underwent hysteroscopic septum resection between January
1991 and December 1996 were studied; nine patients presented with recurrent
abortions, 46 with infertility (26 primary and 20 secondary), one with
dysmenorrhoea and one with an asymptomatic complete septum. Their reproductive
history included 78 pregnancies: 69 (88.4%) abortions, two (2.6%) ectopics, two
(2.6%) preterm deliveries and five (6.4%) term deliveries. In patients with
infertility, the incidence of unexplained infertility was 19.6% and the incidence
of endometriosis was 26.1%. After hysteroscopic septum resection, 42 patients
were interested in pregnancy. All patients with recurrent abortions conceived
spontaneously. Twenty-one (63.6%) infertile patients achieved a pregnancy, 13
(61.9%) of them after treatment with various assisted reproduction techniques.
The reproductive outcome after septum resection yielded 44 pregnancies, including
three sets of twins and one set of triplets reduced to twins: 11 (25%) abortions,
one (2.3%) ectopic pregnancy, two (4.5%) preterm deliveries (both twins), 28
(63.7%) term deliveries and two (4.5%) as-yet ongoing pregnancies. It seems that
the hysteroscopic treatment of uterine septum has a beneficial effect on
pregnancy outcome. A septate uterus does not seem to be an infertility factor.
The achievement of pregnancy is normal in patients with recurrent abortions,
while the chances of conception in patients with infertility seem to be similar
to those for the general infertile population.
PMID- 9647546
TI - The role of monocyte chemotactic protein-1 in intraperitoneal adhesion formation.
AB - Abdomino-pelvic adhesions arise from infection, endometriosis, or peritoneal
injury during surgery, and represent a significant source of morbidity in women
of reproductive age. Monocyte chemotactic protein-1 (MCP-1) plays a role in the
chemotaxis of mononuclear cells and fibroblasts in a murine wound repair model.
To evaluate the role of MCP-1 in intraperitoneal adhesion formation, we
investigated peritoneal fluid MCP-1 levels of women undergoing laparoscopy.
Patients without endometriosis were divided into two groups: normal fertile women
undergoing bilateral tubal ligation without intraperitoneal adhesions (n=14) and
women with pelvic adhesions (n=8). Patients with endometriosis were arranged into
two groups: women with (n=17) and without (n=17) adhesions. Peritoneal fluid MCP
1 levels were quantified using an enzyme-linked immunosorbent assay (ELISA).
Peritoneal biopsy samples were immunostained for the detection of MCP-1 protein
and macrophages, and were also processed for the presence of MCP-1 mRNA
expression. Among women without endometriosis, the median peritoneal fluid MCP-1
level was 144 pg/ml (range 54-261) in women without adhesions and was 336 pg/ml
(range 130-2494) in women with adhesions (P=0.01). There was a significant
correlation between adhesion scores and MCP-1 levels (r=0.50; P=0.018). Among
women with endometriosis, peritoneal fluid MCP-1 levels significantly correlated
with the stage of the disease. The presence or absence of adhesions did not
significantly affect the peritoneal fluid MCP-1 levels in this group of women. In
summary, we have found that women with adhesions have elevated peritoneal fluid
MCP-1 levels. However, we were not able to show an incremental effect of
adhesions on peritoneal fluid MCP-1 levels of patients with endometriosis. Thus,
we conclude that factors besides the intraperitoneal adhesions contribute to the
elevated peritoneal fluid MCP-1 levels in patients with endometriosis.
PMID- 9647547
TI - Cost considerations with infertility therapy: outcome and cost comparison between
health maintenance organization and preferred provider organization care based on
physician and facility cost.
AB - Of 98 retrospectively selected patient couples insured under one scheme (group I)
who, based on performance of a hysterosalpingogram (HSG), were assumed to be
under active infertility care, 96 were confirmed as infertile. These were matched
by date, patient age and time of HSG to 96 patients under infertility care (group
II). Both patient populations were then prospectively evaluated for outcome and
cost of treatment. Total physician charges for groups I and II were similar.
However, charges per achieved clinical pregnancy were higher in group I than
group II since group I patients demonstrated a lower pregnancy rate (28/96, 29%)
than group II patients (41/96, 43%) (P=0.05). Within group I, pregnancy rates
were identical, whether treatment was provided by generalists or subspecialists.
In group II, all care was provided by specialists. The number of days of
treatment did not vary between groups I and H, though generalists in group I
provided significantly fewer treatment days than specialists in either group I
(P=0.003) or in group II (P=0.021). This was primarily due to a significantly
higher patient drop-out rate in group I patients, and especially amongst those
who received care from generalists (P < 0.0019). Group I patients also
encountered significantly more surgical procedures than group H patients
(P=0.0016). If physician charges are discounted and customary surgical facility
costs are added, the actual cost structure for fertility care in group I patients
was dramatically higher than in group II patients. The most cost-effective format
to provide infertility care of high quality appears to be a managed care setting
in which subspecialists provide a majority of care and in which patient choice is
restricted to those subspecialists.
PMID- 9647548
TI - Treatment-independent pregnancy rate in patients with severe reproductive
disorders.
AB - A long waiting list for in-vitro fertilization (IVF) offers the possibility to
study treatment-independent pregnancy rates in patients with severe reproductive
disorders. We performed a retrospective cohort study with a nested case-control
design in which the cases achieved a spontaneous pregnancy while on the waiting
list for IVF, or for IVF with intracytoplasmic sperm injection (ICSI), and the
controls did not become pregnant while on the waiting list. Spontaneous
pregnancies occurred in 76 of 1391 patients on the waiting list. Significant
differences between pregnant and non-pregnant patients were found for duration of
subfertility (couples on the IVF waiting list), and for progressive sperm
motility and basal 17beta-oestradiol (couples on the ICSI waiting list). The 12
months cumulative pregnancy rate for patients on the waiting list was 2.4% (95%
CI 1.2-3.9%) for tubal subfertility patients, 5.9 % (3.7-8.7%) for longstanding
unexplained subfertility patients, and 6.6% (4.5-9.3%) for male subfertility
patients. Of the 76 control patients, 21% of tubal subfertility patients, 18% of
unexplained subfertility patients, and 17% of male subfertility patients achieved
a pregnancy in their first IVF or ICSI treatment cycle. We confirm that the
treatment-independent pregnancy rate in patients with severe reproductive
disorders is low. More than 75% of the spontaneous pregnancies in the tubal
subfertility and unexplained subfertility couples occurred during their first
three months on the waiting list, whereas spontaneous pregnancy rate in male
subfertility couples showed a more gradual but persisting increase. We conclude
that one cycle of IVF or ICSI is superior to 12 months of expectant management in
patients with severely impaired fertility due to tubal, unexplained or male
factors.
PMID- 9647549
TI - Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of
women using a levonorgestrel-releasing intrauterine system.
AB - This study has examined endometrial tissue in 14 normal women prior to insertion
of a levonorgestrel-releasing intrauterine system (LNG-IUS) and thereafter
longitudinally for up to 12 months post-insertion. The specific endpoints
examined by immunohistochemistry were progesterone receptor (PR) subtypes A + B,
oestrogen receptor (ER) and prostaglandin dehydrogenase (PGDH). Two
antiprogesterone receptor antibodies, one specific to PR(B) subtype and the other
to PR subtype A + B, were employed to examine the localization of both PR
isoforms. The activity of PGDH, a progesterone dependent enzyme, was also
measured. ER and PR(A+B) and PR subtype B were significantly down-regulated in
glands and stroma in the presence of continuous intrauterine LNG delivery. There
was an apparent increase in PR(A) immunoreactivity in endometrial glands between
6 and 12 months post-insertion. Consistent with down-regulation of both isoforms
of PR was reduced glandular PGDH immunostaining following LNG-IUS insertion, and
PGDH activity (as measured by metabolism of excess substrate in vitro).
Furthermore, PGDH activity, known to be localized in the glands, significantly
increased (P < 0.05) at 12 months post-insertion, coinciding with the observed
increase in glandular PR(A+B) immunoreactivity at this time. Since the LNG-IUS
suppresses the PR(B) so strongly, PR(A) is likely to be the subtype that mediates
long term LNG action in the endometrium. PR(B) is the more suppressed of the two
subtypes, and only PR(A) rises along with PGDH activity. Alterations to normal
endometrial morphology and function, e.g. perturbation of normal sex steroid
receptor expression, following exposure to high concentrations of local LNG, may
play a role in the aetiology of bleeding disorders associated with the LNG-IUS.
Further elucidation of local uterine mediators involved in the mechanism of
bleeding problems is required.
PMID- 9647550
TI - Morphological and functional features of endometrial decidualization following
long-term intrauterine levonorgestrel delivery.
AB - Irregular bleeding remains a common reason for the discontinuation of progestin
only contraception. The levonorgestrel releasing intrauterine system (LNG-IUS)
has profound morphological effects upon the endometrium. Specific features are
gland atrophy and extensive decidual transformation of the stroma. Morphological
changes in the endometrium may be associated with perturbation of mechanisms
regulating normal endometrial function. This study describes endometrial stromal
and glandular features prior to and up to 12 months following insertion of the
LNG-IUS. Comparison is made with first trimester decidua. In order to elucidate
further mechanisms governing endometrial function with local intrauterine
delivery of LNG, we here report histological features consistent with
decidualization; a significant increase in granulocyte-macrophage colony
stimulating factor (GM-CSF) immunoreactivity in decidualized stromal cells;
glandular and stromal prolactin receptor expression and an infiltrate of CD56 +
large granular lymphocytes and CD68 + macrophages. We are unaware of previous
reports which have documented longitudinally both morphological and functional
observations in endometrium exposed to local intrauterine levonorgestrel
delivery. These studies demonstrate that long-term administration of intrauterine
levonorgestrel results in features of altered morphology and function. No
correlation was apparent between the end points in the study and the bleeding
patterns described by the subjects. Further evaluation of these features in the
context of menstrual bleeding experience may contribute to a better understanding
of this troublesome side-effect which often leads to dissatisfaction and
discontinuation of the intrauterine system.
PMID- 9647551
TI - Low dose of cyproterone acetate and testosterone enanthate for contraception in
men.
AB - After a control phase, 10 normal men received cyproterone acetate (CPA) at a dose
of 25 mg/day (CPA-25; n=5) or 12.5 mg/day (CPA-12.5; n=5) plus testosterone
enanthate (TE) 100 mg/week, for 16 weeks. Throughout the study sperm counts were
performed every 2 weeks, and luteinizing hormone (LH), follicle stimulating
hormone (FSH), testosterone, biochemical and haematological tests were performed
every 4 weeks. All five men in group CPA-25 and three men in group CPA-12.5
achieved azoospermia. One man in group CPA-25 was azoospermic by week 12 of
hormone administration, but had a sperm count of 0.1 x 10(6)/ml at week 16. Time
to azoospermia was 9.0+/-1.3 and 8.7+/-0.7 weeks in groups CPA-25 and CPA-12.5
respectively. Gonadotrophins were decreased by week 4 of hormone administration,
remained around the minimum detectability of the assay for the duration of
hormone administration and returned to baseline after stopping hormone
administration. Testosterone values did not change. No change in any biochemical
parameters was found. Haematological parameters were decreased at week 16 of
hormone administration and returned to baseline after stopping hormone
administration. In conclusion, these results suggest that an hormonal regimen
consisting of testosterone plus a progestin with anti-androgenic properties holds
promise as an effective, safe and reversible male contraceptive.
PMID- 9647552
TI - Successful testicular sperm extraction (TESE) in spite of high serum follicle
stimulating hormone and azoospermia: correlation between testicular morphology,
TESE results, semen analysis and serum hormone values in 103 infertile men.
AB - Spermatozoa recovered from testicular biopsies can be used through
intracytoplasmic sperm injection (ICSI) to achieve a pregnancy. To assess the
likelihood of successful testicular sperm extraction (TESE) in men suffering from
severe oligo- or azoospermia, bilateral biopsy specimens were obtained. Following
semi-thin sectioning, the morphology of testicular samples was graded according
to a modified Johnsen score. TESE was performed in parallel to this histological
examination. The number of isolated spermatozoa was assessed in a
semiquantitative way. From 103 patients investigated, 64 (62.1%) showed
azoospermia in a preceding semen analysis and 29 (28.2%) patients had sperm
concentrations between 0.1 and 1 x 10(6)/ml. In 10 patients who had higher sperm
counts, most spermatozoa were non-motile. Spermatozoa could be detected after
TESE in the testicular tissue of 49 (77%) azoospermic men. When follicle
stimulating hormone (FSH) concentration was normal, most patients had detectable
spermatozoa after TESE. Nearly one-third of patients with mildly elevated FSH had
no spermatozoa. Thirty-nine percent of patients in whom FSH was elevated to more
than twice normal and 50% of patients with grossly elevated FSH had no detectable
spermatozoa. In all, 82.8% of men with sperm concentrations between 0.1 and
1x10(6)/ml in their ejaculate showed spermatozoa in the tissue sample after TESE.
Our data demonstrate that, contrary to previous recommendations, infertile men
with azoospermia and high FSH values should be reconsidered for testicular
biopsy, provided that tissue samples can be cryopreserved for later TESE/ICSI
treatment.
PMID- 9647553
TI - A logistic regression model including DNA status and morphology of spermatozoa
for prediction of fertilization in vitro.
AB - To determine predictive values of routine semen analysis, sperm morphology
evaluation using strict criteria and DNA status for in-vitro fertilization (IVF),
66 consecutive couples undergoing IVF in a university hospital IVF programme were
prospectively investigated. Semen samples from 66 men were evaluated by routine
semen analysis, morphology evaluation using strict criteria and acridine orange
staining for determination of DNA status. A new technique is described for
acridine orange scoring which consisted of evaluation of two smears per case,
with and without heat treatment. Resistance to heat-provoked denaturation was
determined by the difference between two evaluations. A logistic regression model
was built and receiver operating characteristic curves were constructed to
determine the threshold values and to compare diagnostic properties. Morphology
evaluation using strict criteria and concentration of progressively motile
spermatozoa were found to be the principal parameters determining the sperm
fertilizing capacity in vitro. The logistic regression model composed of
morphology evaluation using strict criteria and acridine orange score had a
powerful diagnostic capability for prediction of fertilization in vitro.
PMID- 9647554
TI - The effects of antioxidant supplementation during Percoll preparation on human
sperm DNA integrity.
AB - The integrity of sperm DNA is crucial for the maintenance of genetic health. A
major source of damage is reactive oxygen species (ROS) generation; therefore,
antioxidants may afford protection to sperm DNA. The objectives of the study
were, first, to measure the effects of antioxidant supplementation in vitro on
endogenous DNA damage in spermatozoa using the single cell gel electrophoresis
(comet) assay and, second, to assess the effect of antioxidant supplementation
given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150
patients were prepared by Percoll centrifugation in the presence of ascorbic acid
(300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or
acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation.
DNA strand breakage was measured using the comet assay. Sperm DNA was protected
from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60
microM) and urate (400 microM). These antioxidants provided protection from
subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or
ascorbate and alpha tocopherol together induced further DNA damage.
Supplementation in vitro with the antioxidants ascorbate, urate and alpha
tocopherol separately has beneficial effects for sperm DNA integrity.
PMID- 9647555
TI - Enhancement of motility and acrosome reaction in human spermatozoa: differential
activation by type-specific phosphodiesterase inhibitors.
AB - Inhibition of sperm phosphodiesterase (PDE) has been shown to increase cAMP
concentrations and stimulate motility and the acrosome reaction. While several
PDE genes exist in mammals, little is known about the physiological role of PDE
forms expressed in human spermatozoa. Using type-selective inhibitors, we
identified two of the PDE forms expressed in human spermatozoa and studied their
involvement in sperm function. Selective inhibitors of calcium-calmodulin
regulated PDE1 (8-methoxy-isobutyl-methylxanthine) and cAMP-specific PDE4 (RS
25344, Rolipram) were used to study PDE forms in human sperm extracts. 8-MeIBMX
and Rolipram/RS-25344 inhibited sperm PDE activity by 35-40 and 25-30%
respectively. Subcellular fractionation of the sperm homogenate suggests these
pharmacologically distinct forms may be located in separate cellular regions. To
evaluate the functional significance of different PDE forms, the effect of type
specific PDE inhibition on sperm motility and the acrosome reaction was examined.
PDE4 inhibitors enhanced sperm motility over controls without affecting the
acrosome reaction, while PDE1 inhibitors selectively stimulated the acrosome
reaction. These data indicate at least two distinct PDE types exist in human
spermatozoa. Our findings also support the hypothesis that PDE subtypes affect
sperm function by regulating separate pools of cAMP and may ultimately offer
novel treatments to infertile couples with abnormal semen parameters.
PMID- 9647556
TI - Quantitative sperm mucus penetration: modified formulae for calculating
penetration efficiency.
AB - In 1980 Katz et al. derived a formula for the percentage of successful collisions
(PSC) as a quantitative measure of sperm-cervical mucus penetration efficiency.
The use of PSC waned after its validity was questioned by reports of values >100%
and the observation that PSC varied with the cross-sectional area of the mucus
column. The aim of the present study was to develop a more accurate measure of
mucus penetration efficiency by correcting the original formula for the effects
of sperm depletion in the semen reservoir. Two formulae were derived using
different models for the sperm-mucus interaction: (i) each motile spermatozoon
was assumed to have an equal chance of mucus penetration on collision; (ii) a
select subpopulation of spermatozoa was assumed to penetrate with 100% efficiency
on collision. Both modified formulae gave PSC values higher than the original
estimates. Under the experimental conditions employed in this work, where large
capillaries were used, the depletion corrections ranged from 4 to 46% (n=8, mean
20%) for model (i) and from 190 to 320% (n=8, mean 250%) for model (ii). The
invariance of PSC (ii) results with respect to capillary cross-sectional area
(1.52 mm2, 31.1%; 5.4 mm2, 28.2%) suggests that the assumptions of model (ii)
provide the more accurate description of the sperm-mucus interaction.
PMID- 9647557
TI - The mini-micro-epididymal sperm aspiration for sperm retrieval: a study of
urological outcomes.
AB - Epididymal sperm aspiration and in-vitro fertilization (IVF) with
intracytoplasmic sperm injection is an established treatment for obstructive
azoospermia. Sperm aspiration is performed with either an incision or
percutaneously. To control costs, minimize morbidity and retain the advantages of
both approaches, we developed a mini-incision technique for epididymal aspiration
and here report sperm retrieval and procedure-related outcomes. Twenty-six
consecutive patients with obstructive azoospermia underwent epididymal sperm
retrieval through a 1 cm incision with local anaesthesia to provide spermatozoa
for concurrent IVF cycles. The quality of retrieved spermatozoa, the quantity of
spermatozoa cryopreserved as well as anaesthetic requirement, recovery time and
patient satisfaction were evaluated. Fresh epididymal spermatozoa were retrieved
in 25 of 26 (96%) patients. In one patient, testicular sperm extraction was
necessary. Excess motile spermatozoa were cryopreserved in 24 of 26 (92%)
patients; a mean total motile count of 4.8x10(6) motile spermatozoa were banked.
The procedure was performed with 62% of patients receiving minimal i.v. sedation.
Post-procedure recovery was rapid, with a median time to return to work of 2.0
days with a median of 2.0 pain pills taken. Procedure-related satisfaction was
high. The mini-micro-epididymal sperm aspiration achieves the goals of reliable
retrieval of abundant epididymal spermatozoa with a single, minimally morbid
procedure. It appears to combine the advantages of the incision and percutaneous
approaches.
PMID- 9647558
TI - A comparison between open and percutaneous needle biopsies in men with
azoospermia.
AB - Open testicular biopsy is a classic method of investigation in men with
azoospermia. Recently, percutaneous needle biopsy of the testis has been used in
attempts to obtain material for histopathological diagnosis in such cases and to
retrieve spermatozoa for intracytoplasmic sperm injection (ICSI). To determine
whether a 19 gauge (G) and a 21G butterfly needle could be used for percutaneous
aspiration of testicular tissue to determine the presence of mature spermatids
and assess spermatogenesis, 10 patients (16 testes) and 12 patients (17 testes)
underwent 19G or 21G needle biopsy respectively, immediately followed by open
testicular biopsy, with both procedures under local anaesthesia. Biopsy with each
needle size was compared with open biopsy. With the 19G needle, in the 14 cases
where material was obtained there was full agreement with open biopsy regarding
the presence or absence of mature spermatozoa, whereas with the 21G needle only
nine of the 13 biopsies yielding material were predictive in this respect. Each
needle size correlated poorly with open biopsy regarding evaluation of
spermatogenesis. We conclude that percutaneous biopsy with a 19G butterfly needle
is a quick and reliable method for demonstrating spermatozoa for ICSI. But for a
detailed histopathological diagnosis, however, the needle biopsies gave poor
results, whereas the material from the open testicular biopsies was assessable.
PMID- 9647559
TI - Androgen action during male sex differentiation includes suppression of cranial
suspensory ligament development.
AB - The cranial suspensory ligament is located on the border of the cranial
(mesonephric) mesentery in adult female mammals, which runs between the cranial
pole of the internal genitalia and the dorsal abdominal wall. Absence of the
cranial suspensory ligament in male mammals depends upon exposure of its
primordium to fetal testicular androgens and is a prerequisite for testis
descent. Female rats were exposed to 5alpha-dihydrotestosterone propionate at
different stages of genital development, and cranial suspensory ligament
development was studied in neonatal and in adult animals. Androgens suppressed
cranial suspensory ligament development when exposure started during the early
stages of genital development, until day 19 postconception (pc). Androgen
receptor expression was immunohistochemically detected in the cranial mesentery
of both sexes from day 16 pc onwards. A decrease of androgen receptor expression
in female fetuses from day 18 pc onwards coincided with the appearance of a
differentiated cranial suspensory ligament, as evidenced by the expression of two
cell differentiation markers: alpha-smooth muscle (alpha-SM) actin and desmin.
alpha-SM actin was located on the outer border of the cranial mesentery of both
sexes at day 17 pc, and expression increased only in female fetuses. On day 19
pc, desmin expression was also detectable in the a-SM actin-positive cells.
Proliferation and apoptosis indices of cells in the cranial mesentery, as
analysed by 5'-bromodeoxyuridine incorporation and by detection of DNA strand
breaks (TUNEL method) respectively, did not show any difference between the
sexes, neither on day 17 nor on day 18 pc. Since primordial cells of the cranial
suspensory ligament highly express the androgen receptor during the period of
gestation when androgens can suppress cranial suspensory development, altered
morphogenesis of these cells may be a direct consequence of androgen action.
PMID- 9647560
TI - Continuing the debate on empty follicle syndrome: can it be associated with
normal bioavailability of beta-human chorionic gonadotrophin on the day of oocyte
recovery?
AB - This paper describes our experience with four ovarian stimulation in-vitro
fertilization (IVF) cycles in which we failed to retrieve oocytes despite normal
bioavailability of beta-human chorionic gonadotrophin (beta-HCG) in patients'
blood 35 h after HCG administration. In three cases, the oocyte recovery
procedure was interrupted, a second dose of HCG was administered and 24 h later
mature oocytes were collected from two of the patients. In the first case, the
three metaphase II oocytes collected fertilized after intracytoplasmic sperm
injection (ICSI) and two cleaved grade three embryos were transferred but
pregnancy did not ensue. In the second case, six out of eight metaphase II
oocytes fertilized and cleaved following ICSI, leading to transfer of one grade
two and two grade three embryos. This resulted in a clinical pregnancy which at
the time of this report is ongoing. A similar rescue protocol was used for the
third case who had empty follicle syndrome (EFS) in her previous treatment cycle
but only cumulus-corona complexes were aspirated. Five additional patients who
had EFS before instituting pregnancy diagnostic test screening have had further
treatment cycles in which oocytes were collected but pregnancy did not ensue. We
conclude that normal bioavailability of beta-HCG on the day of oocyte recovery
does not exclude the diagnosis of EFS. EFS does not predict a reduced fertility
potential in future cycles, although it may recur due to a biological abnormality
in the availability of mature oocytes that are retrievable. In such patients,
oocyte donation may offer the chance of achieving a pregnancy.
PMID- 9647561
TI - Differential responses of granulosa cells from small and large follicles to
follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity:
effects of tumour necrosis factor-alpha.
AB - This study determined effects of follicle stimulating hormone (FSH) alone and in
combination with tumour necrosis factor (TNF), on granulosa cells from small (5
10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal
phases of the cycle and during periods of acyclicity. Granulosa cells were
collected from ovaries of premenopausal women undergoing oophorectomy. The cells
were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the
presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and
96 h after culture and progesterone, oestradiol and cAMP in media were measured
by radioimmunoassays. FSH stimulated the accumulation of oestradiol from
granulosa cells of small follicles during the follicular and luteal phases but
not during acyclicity; and TNF reduced oestradiol accumulation in the presence of
FSH. Interestingly, in granulosa cells from small follicles, progesterone and
cAMP secretion increased in response to FSH and neither was affected by TNF.
Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in
granulosa cells from small follicles. FSH stimulated oestradiol production by
granulosa cells of large follicles obtained only during the follicular phase of
the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells
obtained from large follicles during the luteal phase and during acyclicity did
not accumulate oestradiol in response to FSH. However, FSH increased progesterone
and cAMP secretion by granulosa cells obtained from large follicles during the
follicular and luteal phases. During the luteal phase alone, TNF in combination
with FSH increased progesterone accumulation above that of FSH alone. FSH did not
increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained
from large follicles during acyclicity. Thus, FSH increases progesterone,
oestradiol and cAMP secretion by granulosa cells of small follicles during the
follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol
secretion specifically in those cells. In large follicles, FSH-stimulated
granulosa cell secretion of oestradiol is limited to the follicular phase and
this effect can be inhibited by TNF. In addition, when granulosa cells of large
follicles do not increase oestradiol secretion in response to FSH, TNF stimulates
progesterone secretion.
PMID- 9647562
TI - Recombinant luteinizing hormone as a survival and differentiation factor
increases oocyte maturation in recombinant follicle stimulating hormone
supplemented mouse preantral follicle culture.
AB - The effects of recombinant luteinizing hormone (rLH) and recombinant follicle
stimulating hormone (rFSH) both separately and together were analysed on the in
vitro maturation of a well-defined class of mouse early preantral follicles.
Metaphase-II (MII) oocytes were only obtained when rLH or rFSH or a combination
of both hormones was added to a standard rich culture medium at constant doses
throughout the culture period. Without gonadotrophins only 8% of the follicles
reached day 12 of culture. Follicle survival was optimal (between 90 and 100%)
when rFSH was used; significantly fewer follicles were kept intact when rLH was
added as the only supplement (54%; P < 0.001). Theca cells played a fundamental
role in follicle survival when rLH was the only supplement. Presence of rLH
significantly influenced the formation of antral-like cavities: on day 12, 59% of
follicles cultured with rLH + rFSH had a large cavity, as compared with only 21%
in cultures with rFSH only (P < 0.0001). The rHCG stimulated germinal vesicle
breakdown rate from the different gonadotrophin-supplemented cultures on day 12
was not significantly different (FSH: 89%; LH: 70%; FSH/LH: 83%). However,
addition of rLH to rFSH did significantly improve (P < 0.05) the completion of
the first meiotic division up to the MII stage (FSH: 46%; LH: 39%; FSH/LH: 76%).
Interfollicle differences in steroid production were very large and depended on
the presence of theca cells and on the kind of gonadotrophin supplemented.
Without theca cells, oestrogen concentrations in rFSH-supplemented cultures were
100 times lower than their theca-containing counterparts during the entire
culture period. From culture day 9 onwards most conditioned media had increased
basal progesterone concentrations. This study points up the in-vitro role of LH
on the differentiation of follicle-like structures and the oocyte's meiotic
maturation and suggests an important role for theca cells in providing modulators
of in-vitro gonadotrophin action.
PMID- 9647563
TI - Human ovarian granulosa cells and follicular fluid indices: the relationship to
oocyte maturity and fertilization in vitro.
AB - The study investigates the correlation between oocyte maturity and fertilization
and a variety of hormonal parameters in follicular fluid and ovarian granulosa
cells. A methodology for purification of granulosa cells from contaminating blood
cells is also established. A total of 63 follicular aspirates were collected at
oocyte retrieval from 30 women superovulated using the long luteinizing hormone
releasing hormone (LHRH analogue)/human menopausal gonadotrophin regimen.
Oestradiol, progesterone, testosterone and human chorionic gonadotrophin (HCG)
were quantified in follicular fluid and granulosa cells were immunostained for
human chorionic gonadotrophin. Immunopurification of granulosa cells from
contaminating blood cells was performed. HCG in follicular fluid was
significantly high in follicles yielding immature (grade 3) oocytes (P=0.002);
there was no correlation with fertilization. Aspirates from follicles containing
mature (grade 1) oocytes and oocytes that subsequently fertilized had
significantly more granulosa cells immunobound to HCG (P < 0.001, P=0.02).
Moreover, the immunomagnetic purification technique provided >98% pure population
of granulosa cells. The data demonstrate that HCG in follicular fluid and on
granulosa cells may help to predict oocyte maturity and fertilization.
Furthermore, immunomagnetic beads provide a reliable procedure for the
purification of ovarian granulosa cells.
PMID- 9647564
TI - The impact of cellular fragmentation induced experimentally at different stages
of mouse preimplantation development.
AB - It has been demonstrated previously that removal of acellular debris from the
preimplantation mouse embryo is beneficial for subsequent development to the
hatched blastocyst stage. We have studied the impact of cellular fragmentation
induced in the mouse embryo during the late pronuclei and 8-cell stages on the
hatching frequency and total cell number at the blastocyst stage. At the late
pronuclei stage about one-quarter of the cytoplasm was removed from embryos in
the experimental group, in four to six steps, thus creating four to six
cytoplasts that were subsequently returned as anucleated fragments under the zona
pellucida. Embryos with one-quarter of the cytoplasm removed and with intact
cytoplasm after partial zona dissection (PZD) served as controls. At the 8-cell
stage, embryos with their nucleoplast removed from two blastomeres served as an
experimental group. Groups of embryos with part of the cytoplast removed from two
blastomeres (nucleated fragments), embryos with two blastomeres removed and
embryos after PZD alone served as controls. After manipulation all embryos were
left in culture and analysed at about 100 h after human chorionic gonadotrophin
administration. Fragments induced at the late pronuclei stage did not participate
in compaction and were often spontaneously expelled from the embryo during
hatching. Neither embryo hatching rate nor total cell number was affected when
compared with zygotes with reduced cytoplasm. Although both nucleated and
anucleated fragments induced at the 8-cell stage participated in recompaction,
hatching was not compromised and there was no interference in further development
as assessed by the cell number or hatching rate at the blastocyst stage, as
compared with embryos with blastomeres removed. We conclude that anucleated
cellular fragments formed in an otherwise healthy embryo, both before and after
acquisition of the ability for compaction, are benign and that their removal
provides no benefit for embryo development, at least to the hatched blastocyst
stage.
PMID- 9647565
TI - Endogenous folic acid is essential for normal development of preimplantation
embryos.
AB - Preimplantation mammalian embryos develop with a high degree of autonomy. To
date, there have been no unequivocal demonstrations of a requirement for vitamins
in preimplantation embryo development. Reduced folic acid acts as an important
methyl donor in many reactions including the synthesis of thymidine. Thymidine
does not accumulate in cells so it might be expected that significant amounts of
reduced folate would be required to support the exponential increase in DNA
synthesis that occurs during early embryo development. The reduction of folate is
catalysed by dihydrofolate reductase (EC 1.5.1.3) which is selectively inhibited
by the anti-cancer drug methotrexate. Methotrexate caused a dose-dependent
inhibition of cell division in 1-cell, 2-cell and 8-cell mouse embryos with 50%
inhibition of division occurring at concentrations of 1-10 microM. At a
concentration of 0.1 microM only minimal inhibition of the initial cell division
occurred, but continuous culture in this concentration of methotrexate completely
inhibited further cell divisions. This suggests that most of the exogenous store
of reduced folates was used in the first round of cell division. The effects of
methotrexate were apparently primarily due to thymidine starvation, since a 10
fold excess of thymidine over methotrexate in culture media reversed the
inhibition of development. Supplementing media with folic acid had no beneficial
effect on the rate at which zygotes produced by in-vitro fertilization developed
to the blastocyst stage. It is concluded that the development of the early embryo
has an absolute requirement for reduced folate for thymidine synthesis which is
met entirely by endogenous sources.
PMID- 9647566
TI - DNA strand breaks and phosphatidylserine redistribution in newly ovulated and
cultured mouse and human oocytes: occurrence and relationship to apoptosis.
AB - This study determined the occurrence of two molecular markers of apoptosis,
chromosomal DNA strand breaks and oolemma phosphatidylserine redistribution, in
>200 uninseminated and unfertilized human oocytes, and >800 newly ovulated and
cultured mouse oocytes. DNA breaks were analysed by terminal deoxynucleotidyl
transferase-mediated dUDP nick-end labelling (TUNEL) and phosphatidylserine by
annexin V staining, with imaging by conventional epifluorescence and scanning
laser confocal fluorescence microscopy. More than 300 intact and 500 fragmented
mouse oocytes were examined at 24 h intervals during 6 days of culture in three
different types of medium. For the human, 205 oocytes were examined at retrieval
or at 24 h intervals during 7.5 days of culture in two types of medium. The
perifollicular vascularity and the dissolved oxygen content of follicular fluid
were determined for most of the follicles from which human oocytes were derived.
The results demonstrate that TUNEL fluorescence of metaphase II (MII) chromosomes
and annexin V staining of the oolemma in newly ovulated and cultured mouse and
human oocytes are rare, and, when detected, are not spatially or temporally
related. This finding also applied to mouse oocytes that fragmented during
culture and exhibited morphological features that grossly resembled apoptotic
body formation. In contrast, TUNEL but not annexin V staining occurred in the
first polar body of a relatively high proportion of newly ovulated mouse oocytes,
but was rarely detected in newly aspirated human oocytes. For the human, the
occurrence of MII chromosomal TUNEL fluorescence was patient-specific and
unrelated to perifollicular vascularity or dissolved oxygen content of the
corresponding follicular fluid. The pattern of chromosomal TUNEL fluorescence
observed in the first polar body and in the MII chromosomes of a very small
number of mouse and human oocytes, especially after many days of culture,
suggests that DNA strand breaks may not arise by apoptosis-associated
endonuclease digestion. The results with these two markers suggest that it is
premature to conclude that apoptosis occurs in ovulated oocytes or that such a
mechanism is involved in the elimination or prevention of fertilization of
oocytes with cytoplasmic or chromosomal defects.
PMID- 9647567
TI - The effects of co-culture with human fibroblasts on human embryo development in
vitro and implantation.
AB - In a human in-vitro fertilization (IVF) programme, the effect of co-culture of
embryos with human fibroblasts was evaluated with respect to pregnancy rate and
embryo development. Patients were included in the study after giving informed
written consent. The IVF treatments were randomly assigned by stratification of
both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no).
After fertilization was established, the zygotes were transferred to a 4-well
dish with or without fibroblasts and cultured for 2 days. On the third day after
ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos
were scored and a maximum of three embryos was transferred. Supernumerary embryos
of good quality were cryopreserved. The design of this study was a group
sequential trial with the objective of detecting differences between pregnancy
rates following IVF with conventional incubation or incubation in co-culture with
fibroblasts. This design included one evaluation at half-way data collection. In
the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture
group. There was no statistically significant difference in pregnancy rate, cell
number and embryo quality between the two groups. The ongoing pregnancy rate per
embryo transfer was 27% in co-culture and 30% in the conventional culture group.
The implantation rates per transferred embryo were 17 and 18% respectively. Using
a multivariate logistic regression model for the probability of ongoing
pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF
attempts, was not statistically significant. In conclusion, co-culture with human
fibroblasts does not contribute to an improvement of embryo quality nor to a
higher pregnancy rate after IVF in an unselected group of patients.
PMID- 9647568
TI - Rescue of implantation potential in embryos with poor prognosis by assisted zona
hatching.
AB - The effect of the assisted zona hatching (AZH) procedure was investigated on 135
cycles with a poor prognosis of pregnancy due to: (i) maternal age > or = 38
years (45 cycles); (ii) three or more failed in-vitro fertilization (IVF)
attempts (70 cycles), and (iii) patients possessing both inclusion criteria (20
cycles). The control groups (113 cycles) included patients possessing the same
characteristics (42, 53 and 18 cycles respectively) and who did not undergo the
AZH procedure. A total of 505 embryos was treated with AZH before transfer,
resulting in: 14, 25 and 6 clinical pregnancies. The percentage of clinical
pregnancies per cycle was significantly higher than controls for the first (31 vs
10% in control 1, P < 0.05) and second groups (36 vs 17% in control 2, P < 0.05).
No significant difference in percentage of clinical pregnancies was found for the
third group (30 vs 6%). Similarly, higher rates of implantation were obtained
(11.5, 15 and 11%) compared to the respective controls (4%, P < 0.02; 6.3%, P <
0.01; and 1.5%). The rate of miscarriage in the AZH groups was similar to that
obtained in the controls (22 vs 21%). Finally, the morphological analysis of the
embryos transferred revealed that the poor prognosis condition is associated to a
significantly slower rate of development and a higher rate of fragmentation. The
present results indicate that AZH procedure improves pregnancy and implantation
rates in patients with a poor prognosis of pregnancy by facilitating the hatching
process in embryos which would otherwise be trapped inside the zona pellucida.
PMID- 9647569
TI - Chromatin decondensation, pronucleus formation, metaphase entry and chromosome
complements of human spermatozoa after intracytoplasmic sperm injection into
hamster oocytes.
AB - Obtaining karyotypes from human spermatozoa after microinjection into Syrian
golden hamster oocytes is difficult and the hitherto reported results are
unsatisfactory. This may be related to the injection and culture technique or to
the high susceptibility of the hamster oocytes to undergo parthenogenetic
activation or both. Therefore, we investigated the hamster oocyte-human sperm
microinjection model using the following two approaches: (i) application of
contemporary techniques for injection (touching the sperm tail) and culture
(hamster embryo culture medium, HECM-3, 10% CO2) and (ii) omission of Ca2+ from
the injection medium. Thus, in the first series of experiments, 252 hamster
oocytes were injected with human spermatozoa. Among the 219 (87%) oocytes that
survived the injection procedure, the mean percentages of male pronucleus
formation [two pronuclei (2PN), two polar bodies (PB)], mitotic metaphase entry
and sperm chromosome spreads were 41.4, 27.8 and 18.2% respectively. Analysis of
the oocytes which failed to develop the male pronucleus following injection
revealed that most of them had developed only the hamster female PN while the
sperm nuclei were either intact or swollen (partially decondensed), indicating
that failure of oocyte activation was not the likely reason for the failure of
male PN formation in these oocytes. In the next series of experiments, sibling
oocytes were alternately injected with spermatozoa suspended either in the
regular (1.9 mM Ca2+) or Ca2+-free injection medium (experiment set 2, n=278). A
significant improvement was noted in the mean percentages of oocytes with 2PN,
2PB, metaphase entry and sperm chromosome spreads in the Ca2+-free group versus
the regular group (2PN, 2PB: 51 versus 36.6%, metaphase entry: 36.3 versus 26.9%
and sperm chromosome spreads: 28 versus 20.4%; all P < 0.04). Thus,
parthenogenetic activation appears to be one of the contributing factors for the
failure of male PN formation after heterospecific hamster ICSI. From these
experiments it can be concluded that application of the advanced injection and
culture techniques and omission of Ca2+ from the injection medium are promising
for the routine application of the hamster oocyte microinjection for karyotyping
of human spermatozoa with poor fertilizing capacity.
PMID- 9647570
TI - Expression of cadherins and CD44 isoforms in ovarian endometrial cysts.
AB - We evaluated the immunohistochemical expression of cadherins and CD44 variants in
20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20
ovarian carcinomas, and the serological and cystic fluid concentrations of
soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20
cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas,
immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44
H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A
difference in immunostaining for E-cadherin was found between endometriomas and
cystadenomas (P < 0.001) and for N-cadherin between endometriomas and carcinomas
(P < 0.001). A difference in CD44H immunostaining was observed between
endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian
tumours and carcinomas. No difference in serum concentrations of soluble E
cadherins and CD44 standard was found between the four groups of tumours. Cystic
fluid concentrations of E-cadherin were lower in endometriomas than in borderline
tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44
standard cystic fluid were found in endometriomas than in other ovarian cysts.
Endometriomas and borderline tumours share alterations of cadherins and CD44
isoforms which may help in the understanding of the aggressive and invasive
potentials of endometriotic cells.
PMID- 9647571
TI - The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women
with or without endometriosis.
AB - The study was undertaken to investigate a possible mechanism for reducing the
phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women
suffering from endometriosis. Peritoneal fluids were collected during laparoscopy
from women undergoing laparoscopic sterilization or from women under
investigation for cause of infertility where the laparoscopic findings were
endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro
with peritoneal fluid with or without lignocaine. Samples from the incubations
were studied daily and the number of viable and dead spermatozoa were counted.
The number of free spermatozoa, not adhered to leukocytes, was significantly
increased when incubated in human peritoneal fluid supplemented with lignocaine.
Thus lignocaine contributes to increasing the number of free spermatozoa and
maintaining the possibility of fertilizing an oocyte. For patients with
endometriosis, treatment with lignocaine might be a means of increasing the
chances of conception. A clinical study is in progress to evaluate this effect in
vivo and to search for alternative methods of assisting the fertilization
process.
PMID- 9647572
TI - Endometriosis and uterine leiomyomata with ovarian granulosa cell tumour.
AB - We report the first known case of right endometrial cyst and multiple uterine
leiomyomata complicated by an ovarian granulosa cell tumour of adult type. A 42
year old woman had an adult type left granulosa cell tumour. Laparoscopy 13 years
earlier had revealed a small endometrial implant on the peritoneum, without
uterine leiomyomata or bilateral ovarian tumours. Findings in this case suggest
that the aetiology of endometriosis and uterine leiomyomata are related to the
presence of an oestrogen-secreting neoplasm and that the presence of a state of
hyperoestrogenaemia due to granulosa cell tumour over several years might have
stimulated the development of endometriosis and leiomyomata.
PMID- 9647573
TI - Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in
the human uterine artery.
AB - The influence of pregnancy on the dilator effects of acetylcholine in the
isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1
microM) produced concentration- and endothelium-dependent relaxation of
norepinephrine (3 microM)-induced contraction. The relaxation was greater in
arteries from pregnant patients (P arteries) than from non-pregnant patients (NP
arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/
2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation
was increased in the presence of superoxide dismutase and greatly reduced in the
presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L
NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide
synthase inhibitors was reversed by L-arginine. We conclude that pregnancy
enhances acetylcholine-induced nitric oxide synthesis and release in the human
uterine artery.
PMID- 9647574
TI - Sex hormone-binding globulin stimulates chorionic gonadotrophin secretion from
human cytotrophoblasts in culture.
AB - The effects of sex hormone-binding globulin (SHBG) on the secretion of human
chorionic gonadotrophin (HCG) and cAMP by cultured human cytotrophoblasts were
investigated. Cytotrophoblasts obtained from normal term placentae were cultured
in serum-free medium with or without the addition of human SHBG. The presence of
SHBG in the medium increased the release of HCG and the accumulation of cAMP.
Ligand-free SHBG was able to raise both HCG and cAMP concentrations and the
maximal response was observed with 1 nM of the steroid-binding globulin. Addition
of either oestradiol or 5alpha-dihydro-testosterone (DHT) to cultures previously
incubated with SHBG in a final molar ratio of 1:10 resulted in a further increase
of HCG and cAMP concentrations. This effect was blocked when cultured placental
cells were exposed to SHBG that was previously saturated with DHT or when
incubated in the presence of steroids only. The results of the present study
provide evidence for the in-vitro regulation of HCG secretion by SHBG and further
support the concept that this steroid-binding protein may act as a mediator of
steroid action at the cellular level. Finally, the increase in cAMP suggests that
SHBG receptor located in the surface of syncytiotrophoblast membranes is coupled
to adenylate cyclase as part of the G-protein receptor family. Our results may
provide new insights into the biological implications of extracellular steroid
binding proteins as well as new perspectives on the endocrinology of pregnancy.
PMID- 9647575
TI - Immunolocalization of Le(y) oligosaccharide in endometrium during menstrual cycle
and effect of early luteal phase mifepristone administration on its expression in
implantation stage endometrium of the rhesus monkey.
AB - Changes in carbohydrate expression on endometrial and blastocyst cell surfaces
may play a critical role in the process of implantation. Le(y) is an
oligosaccharide antigen which has been shown to be involved in blastocyst
attachment in the mouse. In the present study, immunohistochemical distribution
of Le(y) in endometrium during proliferative and secretory phases of normal
menstrual cycles in the rhesus monkey was examined. Endometrial samples were
collected on cycle days 7 (n=4), 13 (n= 4), 16 (n=4), 20 (n=4) and 25 (n=3).
There was a gradual increase of Le(y) in luminal surface from proliferative to
periovulatory (P < 0.001), and from periovulatory to postovulatory (P < 0.05),
phases. Le(y) then remained constant in the midsecretory phase and decreased (P <
0.01) during the premenstrual phase. Le(y) score in glands did not change between
the phases, except in midsecretory phase when it was higher than that in other
phases (P < 0.05). The stromal compartment showed no statistically significant
changes. The profiles of endometrial Le(y) on day 6 after ovulation in mated
fecund cycles with or without early luteal phase mifepristone treatment were also
examined. Females were allowed to cohabit with males during days 8-16 of their
ovulatory cycles and were injected s.c. with vehicle (n=7) only, or with a single
dose of mifepristone (2 mg/kg body weight; n=8) on day 2 after ovulation.
Significant decreases in the area and optical absorption of immunoprecipitate
were observed in the epithelial compartment (P < 0.01) following mifepristone
treatment. There was no change in the stromal compartment either in area or in
optical absorption of immunoprecipitate for Le(y) with or without mifepristone
treatment. The expression of Le(y) in the endometrial epithelial compartment
appears to be influenced by progesterone and may be associated with endometrial
receptivity prior to implantation in the rhesus monkey.
PMID- 9647576
TI - Localization of glutathione S-transferases alpha and pi in human embryonic
tissues at 8 weeks gestational age.
AB - Glutathione S-transferases (GST) are a family of enzymes involved in the
detoxification of xenobiotics. In humans, GST are divided into four different
classes, alpha, mu, pi and theta, with partly overlapping substrate specificity
and a tissue-specific expression pattern. We studied the cellular distribution of
GST alpha and pi in a variety of human embryonic organs obtained from an extra
uterine monozygotic twin pregnancy at 8 weeks' gestational age. Tissues were
fixed in 4% paraformaldehyde and embedded in paraffin. Three 4 microm thick
sections were used, one for routine haematein and eosin staining, the others for
immunohistochemical determination using monoclonal and polyclonal antibodies
against GST alpha and pi, respectively. Both GST alpha and pi were present in
hepatocytes, gastrointestinal epithelium, adrenal gland medulla, and tela
chorioidea in the telencephalon. GST pi, but not alpha, was found in the
epithelium of pancreatic and pulmonary glands, trachea, nephrons and urinary
collecting ducts, as well as in the pia mater of the telencephalon and in
developing nerve tissue in the gastrointestinal muscularis mucosae. In summary,
we have demonstrated that immunoreactive protein for both GST alpha and pi is
expressed in the human embryo at 8 weeks' gestational age. The early expression
of GST alpha and pi in the epithelia of the urinary and digestive tracts and the
respiratory system supports the importance of GST in the detoxification of
potentially toxic or carcinogenic compounds. Our results suggest that the embryo
itself is capable of detoxifying noxious compounds that are generated
intracellularly or that cross the trophoblastic tissue.
PMID- 9647577
TI - Successful pregnancy outcome following Tompkins metroplasty done early in
pregnancy.
AB - A hysterosalpingogram revealed a septate uterus in a 29 year old nulliparous
woman with a history of recurrent pregnancy loss. The patient underwent Tompkins
metroplasty in the proliferative phase of the menstrual cycle. One month after
the operation she presented with a delay in her menses and a positive pregnancy
test. Ultrasound revealed a viable fetus commensurate with 10 weeks gestation,
making the gestation period 5 weeks at the time of surgery. After reviewing the
patient's menstrual history it was found that the period the patient had before
surgery was on time but with unusually minimal bleeding. A repeat ultrasound scan
for anomaly done 7 weeks later was commensurate with 17 weeks gestation. The
patient carried her pregnancy for the first time until approximately 37 weeks
when she delivered by Caesarean section a healthy female baby weighing 3700 g.
PMID- 9647578
TI - Maternal and fetal insulin-like growth factors and their binding proteins in the
second and third trimesters of human pregnancy.
AB - The insulin-like growth factors (IGFs) are mitogenic polypeptides which circulate
bound to a series of at least six binding proteins (IGFBPs). An increasing body
of evidence supports a major role for the IGF in the control of human fetal
growth although normal values in the human fetal circulation have not been
established. In order to provide an accurate reflection of fetal IGFs and IGFBPs
in utero, we have sampled fetal blood direct from the umbilical cord at 18-38
weeks of gestation using the technique of cordocentesis. We have measured IGF-I,
IGF-II and IGFBP 1-3 in 91 fetuses in order to establish concentrations for these
parameters in the second and third trimesters of human pregnancy.
PMID- 9647579
TI - Trends in male:female ratio among newborn infants in 29 countries from five
continents.
AB - We have analysed trends in male:female ratios among newborns between 1950 and
1990 in 29 countries from five continents. The numbers of liveborn males and
females over the period 1950-1994 were derived from the World Health Organization
(WHO) database. Countries for which reliable data were available included 20
major European countries (excluding the former Soviet Union, Albania and a few
small countries), Canada, the USA, selected countries of Central and South
America, Japan, Australia and New Zealand. From the original numbers of males and
females, we computed the proportion of males among liveborns for each country and
for selected broader areas within Europe. In most countries the proportion of
male liveborns was constant during the study period. In particular, the
proportion of male newborns in the European Union was 0.515 in 1950-1954, 0.514
in 1970-1974 and 0.514 in 1990-1994. In the USA, corresponding values were 0.513,
0.513 and 0.512. In Japan the ratios were 0.513 in 1950-1954, 0.516 and 1970-1974
and 0.514 in 1990-1994. Decreasing ratios were observed in some northern and
eastern European countries plus Greece and Portugal and, particularly, in Mexico.
In contrast, the proportion of male liveborns tended to increase in southern
Europe and Australia. Overall, among the 29 countries considered, the proportion
of males declined in 16, increased in six, and remained stable in seven.
PMID- 9647580
TI - Sex ratio associated with timing of insemination and length of the follicular
phase in planned and unplanned pregnancies during use of natural family planning.
AB - This was a multicentred, prospective study of pregnancies among women using
natural family planning. The women maintained natural family planning charts of
the conception cycle, recording acts of intercourse and signs of ovulation
(cervical mucus changes, including peak day and basal body temperature). Charts
were used to assess the most probable day of insemination relative to the day of
ovulation and length of the follicular phase of the cycle. The sex ratio (males
per 100 females) for 947 singleton births was 101.5, not significantly different
from the expected value of 105. The sex ratio did not vary consistently or
significantly with the estimated timing of insemination relative to the day of
ovulation, with the estimated length of the follicular phase or with the planned
or unplanned status of the pregnancy. Although these findings may be affected by
imprecision of the data, the study suggests that manipulation of the timing of
insemination during the cycle cannot be used to affect the sex of offspring.
PMID- 9647581
TI - Seasonality of sex ratio in Germany.
AB - It was investigated whether there is a seasonal variation in sex ratio at birth
in Germany. The analysis was based on records from the German Bureau for
Statistics, covering the period from 1946 to 1995. A highly significant (P < or =
0.001), albeit low-amplitude rhythm was found with two peaks in May and December,
and two nadirs in March and October. No correlations were found between sex
ratios and seasonal birth rates during this period.
PMID- 9647582
TI - Distress level in men undergoing intracytoplasmic sperm injection versus in-vitro
fertilization.
AB - The purpose of this study was to compare the psychological reactions of men
undergoing intracytoplasmic sperm injection (ICSI) (n=18) or in-vitro
fertilization (IVF) (n=22). Men monitored their psychological reactions daily for
one complete treatment cycle from the first day of down-regulation until the
outcome of treatment was known (approximately 52 days). The results showed that
ICSI patients reported marginally more distress on the days prior to retrieval
than the IVF patients. Other than this difference the pattern of results
indicated that the psychological reactions of men undergoing ICSI or IVF were
similar and that there was no need to manage these patients differently during
treatment. However, ICSI patients may benefit from some reassuring comments on
the days prior to retrieval when they showed more anticipatory anxiety.
PMID- 9647583
TI - The right to an heir in the era of assisted reproduction.
AB - The latest remarkable technological advances in assisted reproduction, which
enable cryopreservation of spermatozoa, embryos and ovarian tissue, raise
difficult and debatable legal, social, ethical and moral issues concerning the
right to posthumous reproduction. Furthermore, reports on the attitudes of the
general public and of centres licensed for infertility treatment in the United
Kingdom found that the majority of women and centres support the idea of
posthumous reproduction. In this paper we review the data published on this
issue, and after considering the various aspects, we conclude that each case
should be discussed and authorized by a multidisciplinary committee that includes
physicians, clergy, psychiatrists, psychologists, sociologists and other
appropriate parties. In our opinion, the main principles that should guide this
committee would allow posthumous reproduction in the context of marriage when a
prior consent exists. For unmarried persons, post-mortem donation of gametes
should be done only anonymously, if they are in agreement with existing laws
concerning infertility treatments in every country and after appropriate consent
and proper counselling. Moreover, any case which involves consanguinity or a
possibility of incest should be forbidden, both for ethical and genetic reasons.
In a case of pre-existing siblings, they should be consulted and their informed
consent should be granted in advance so as to avoid legal problems in the
inheritance of property.
PMID- 9647584
TI - Spontaneous conception in subfertile couples.
PMID- 9647585
TI - Variation of sex ratio within very large sibships.
PMID- 9647586
TI - Evaluation of Epstein-Barr Virus infection in hypopharyngeal carcinomas from 37
Japanese patients.
AB - Thirty-seven biopsy specimens from primary sites, 18 surgically removed
metastatic neck nodes, and 18 surgically removed primary sites from 37 patients
with hypopharyngeal carcinoma (HPC) were evaluated for the presence of Epstein
Barr Virus (EBV) infection by in situ hybridization (ISH) and polymerase chain
reaction (PCR). Although some of normal lymphocytes in 6 of 18 metastatic nodes
were positive by ISH, there were no positive results from HPC tumor cells
themselves. Our results indicate that EBV-infected non-neoplastic cells such as
lymphocytes can be a cause of false positivity, if a study were conducted with
PCR alone. Because ISH for EBV-encoded early RNAs was highly sensitive, even more
sensitive than PCR from paraffin-embedded samples in our study, this method
should be the first choice for identification of EBV infection to avoid false
positives.
PMID- 9647587
TI - Chronic mucosal changes of the colon in graft-versus-host disease.
AB - The histologic features of acute graft-versus-host disease (GVHD) of the colon
are well documented, but chronic mucosal changes associated with GVHD are poorly
described. We report here the clinicopathologic findings from five patients with
a history of bone marrow transplantation in which colonoscopic biopsies showed
chronic mucosal changes reminiscent of chronic idiopathic inflammatory bowel
disease (IBD). The patients ranged in age from 2.5 to 31 years. Bone marrow
transplantations were performed for leukemia (3 patients), Hodgkin's disease (1
patient), and metachromatic leukodystrophy (1 patient). Endoscopy was performed
because of complaints of abdominal pain and diarrhea in all of the five patients.
The mean time after transplantation in which histologic features of chronicity
were identified was 5.8 months (range, 3-16 mo). All of the five patients had
prior colonic biopsies showing acute GVHD. One patient had a previous episode of
cytomegalovirus infection. Chronicity was characterized by mild-to-moderate
architectural distortion, ie., villiform surface with crypt branching and
atrophy, similar to that seen in chronic idiopathic IBD. The lamina propria was
hypocellular, with prominent small blood vessels. Focal fibrosis of the lamina
propria was noted. One patient had active cryptitis. Superimposed changes of
acute GVHD were mild to absent. None of the patients had a history of IBD before
receiving the bone marrow transplant. Changes associated with chronicity can be
observed in mucosal biopsy specimens from patients with GVHD. It is uncertain
whether these changes are directly caused by GVHD or are the result of
superimposed infections. The association of chronic mucosal change in the setting
of GVHD with the clinical diagnosis of chronic GVHD needs additional
investigation.
PMID- 9647588
TI - The alpha subunit of inhibin in adrenal cortical neoplasia.
AB - We analyzed 23 adrenal adenomas and 15 adrenal cortical carcinomas by
immunolabeling for the alpha subunit of inhibin, and we then compared the results
with the functional status of the neoplasms. We also studied 19
pheochromocytomas, 30 renal cell carcinomas, and 5 extra-adrenal paragangliomas,
tumors posing differential diagnostic problems with adrenal cortical neoplasms.
Immunolabeling was performed using automated immunohistochemical methods and an
antibody directed against the alpha subunit. Tumors were semiquantitatively
assessed for the number of positive cells. Immunopositivity was obtained in 18
(78%) of 23 adrenal cortical adenomas, 12 (80%) of 15 adrenal cortical
carcinomas, 2 (11%) of 19 pheochromocytomas, 0 of 5 extra-adrenal paragangliomas,
and 0 of 30 renal cell carcinomas. Immunoreactivity was strong in 7 (78%) of 9
adrenal cortical tumors from patients with Cushing's-related or virilizing
symptoms. In contrast, only 4 (14%) of 29 tumors that were clinically
nonfunctioning or associated with hyperaldosteronism demonstrated strong staining
(P < .001). In clinically nonfunctioning tumors, there was a tendency for
increased immunopositivity in tumors from patients with elevated levels of
cortisol, androgen, or their precursors, with four of six tumors having at least
moderate immunopositivity. Similar reactivity was present in only one of eight
tumors from patients with normal laboratory values (P=.091). Moderate or strong
immunopositivity was present in 9 (60%) of 15 adrenal cortical carcinomas,
whereas of the pheochromocytomas, extra-adrenal paragangliomas, and renal cell
carcinomas, only 1 (1.9%) of 54 showed moderate-to-strong reactivity. We conclude
that moderate or strong immunoreactivity for the alpha subunit of inhibin occurs
in adrenal cortical tumors from patients with Cushing's-related or virilizing
symptoms. Immunolabeling for the inhibin alpha subunit is potentially useful in
the differential diagnosis of neoplasms that include adrenal cortical carcinomas.
PMID- 9647589
TI - Multiparametric flow cytometry in the diagnosis and characterization of low-grade
pulmonary mucosa-associated lymphoid tissue lymphomas.
AB - Primary mucosa associated lymphoid tissue (MALT) lymphomas are rare neoplasms
that seem to have a better prognosis than nodal lymphomas. Morphologic diagnosis
of these lesions may be difficult because of features that overlap with those of
benign lymphoid infiltrates. In this study, we assessed the contribution of multi
parametric flow cytometry in demonstrating clonality and further characterizing
pulmonary MALT lymphomas. Based on a clinical or pathologic suspicion of MALT
lymphoma, 3 transbronchial biopsies, 4 fine needle aspirates, 1 core needle
biopsy, and 13 wedge excisions of lung were submitted fresh (unfixed) to our
laboratory for evaluation. Among the 13 cases diagnosed as MALT lymphomas, B-cell
monoclonality was established by identifying expression of a single
immunoglobulin light chain on CD20 or CD19-positive cells in 12 cases. One case
lacked expression of both light chains on B-cells. Of 11 lymphoma cases in which
CD5 and CD10 surface antigens were assessed, no cases expressed CD10, and 1 case
demonstrated weak CD5 expression. Nine of 10 cases studied were diploid and 1
case was hyperdiploid. All of the lymphomas displayed low (< or = 3%) S-phase
fractions consistent with low grade processes. In 10 patients with short follow
up, none died of their disease and the majority had no evidence of lymphoma
dissemination. In seven of the remaining eight cases, B-cells were polyclonal
consistent with reactive processes. In one morphologically reactive case, flow
cytometric analysis was unsuccessful because of poor cell viability. The
pulmonary MALT lymphomas in this study represent a group of B-cell tumors with
distinctive morphologic, immunophenotypic, and cell kinetic characteristics.
Multi-parametric flow cytometry is useful for confirming B-cell monoclonality and
illustrating an antigenic profile compatible with this diagnosis. Flow cytometry
can be particularly helpful when working with small biopsies and cytologic
samples with limited diagnostic material and may abrogate the need for more
aggressive surgical procedures.
PMID- 9647590
TI - Expressions of basic fibroblast growth factor and fibroblast growth factor
receptor mRNA in soft tissue tumors by in situ hybridization.
AB - Basic fibroblast growth factor (bFGF) is a mitogenic and angiogenic polypeptide
produced by diverse cell types, including the cells derived from normal tissue
and neoplastic lesions. To evaluate the possible differential expression of bFGF
in soft tissue tumors, we examined 17 frozen primary soft tissue tumors including
extra-abdominal desmoids, leiomyosarcomas, synovial sarcomas, myxoid
liposarcomas, and alveolar soft part sarcomas by nucleic acid in situ
hybridization. Three of the four leiomyosarcomas and two of the three synovial
sarcomas studied expressed bFGF mRNA, whereas all of the myxoid liposarcomas and
alveolar soft part sarcomas were negative. Two of the leiomyosarcomas were also
positive for FGF receptor mRNA. These results indicated the possibility of an
autocrine or paracrine mechanism in the function of bFGF and also lent support to
the opinion that in situ hybridization is useful for examining cell character.
PMID- 9647591
TI - Neuroendocrine neoplasms arising in inflammatory bowel disease: a report of 14
cases.
AB - Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a
premalignant condition, because these patients are at increased risk of
adenocarcinoma. Neuroendocrine neoplasms (NENs) have rarely been described in
this setting. We evaluated 14 cases of NEN arising in a setting of IBD. All of
the tumors arose in areas involved by IBD, and all showed immunohistochemical or
ultrastructural evidence of neuroendocrine differentiation. The cohort included
seven men and seven women (range, 28-71 yr; median, 43 yr). Eight patients had
Crohn's disease (CD), and six had UC. Duration of disease ranged from 4 months to
50 years (median, 15 yr), with one of unknown duration. Of the eight patients
with CD, five had ileocolitis, one had ileitis, one had colitis, and in one case,
the extent of disease was unknown. Of the six patients with UC, four had
extensive UC, one had left-sided UC, and the extent of UC was unknown in one
case. Reasons for surgery included CD complications (five patients), refractory
disease (three patients), dysplasia/carcinoma (five patients), and incontinence
(one patient). The NENs were well differentiated in 11 cases and poorly
differentiated mixed adenocarcinoma/small cell carcinomas in 3 cases. Tumor sites
included the rectum (six cases), appendix (four cases), small bowel (two cases),
and sigmoid colon (two cases). High-grade dysplasia was present in adjacent
mucosa in four cases, and low-grade dysplasia was present in distant mucosa in
two cases. Two patients with poorly differentiated NENs died from the disease at
3 and 11 months after tumor excision. All of the other patients were alive
without tumor as of last follow-up. We concluded that NENs rarely arise in a
setting of IBD. Most are well-differentiated tumors and are clinically indolent.
Dysplasia is found in adjacent mucosa in more than one-third of cases, suggesting
that neuroendocrine differentiation might evolve from multipotential cells in
dysplastic epithelium.
PMID- 9647592
TI - Minimal carcinoma in prostate needle biopsy specimens: diagnostic features and
radical prostatectomy follow-up.
AB - Prostate cancer screening and early detection efforts have resulted in the
identification of smaller volume carcinomas of the prostate. We evaluated the
diagnostic features of minimal (< 1 mm) carcinoma in sextant needle biopsy
specimens of the prostate and in follow-up analyzed the features of the
corresponding carcinomas in the whole gland. We reviewed specimens from 50
consecutive patients who had minimal carcinoma in needle biopsy tissue and who
had undergone radical prostatectomy. Histologic grade, tumor size, pathologic
stage, and margin status of the 50 carcinomas in the whole gland in which the
carcinoma size was minimal in the sextant needle biopsy specimen were compared
with those of 50 carcinomas in the whole gland in which carcinoma size was
greater than 1 mm in the needle biopsy specimen. The most common morphologic
features of these minimal carcinomas were nucleomegaly (96%), infiltrative growth
pattern (88%), intraluminal secretions (78%), prominent nucleoli (64%),
associated high-grade prostatic intraepithelial neoplasia (40%), amphophilic
cytoplasm (36%), hyperchromatic nuclei (30%), and intraluminal crystalloids
(22%). Perineural invasion (2%), collagenous micronodules (2%) and mitotic
figures (2%) were uncommon. The mean tumor volume in the whole gland of
carcinomas corresponding to minimal carcinoma in a needle biopsy specimen was
significantly smaller (P=.029) at 1.1 mL than it was in carcinomas with tumor
greater than 1 mm in the needle biopsy specimen at 1.6 mL, but other pathologic
features of carcinoma in the whole gland were not significantly different. In
conclusion, a constellation of morphologic attributes is important for
establishment of a diagnosis of minimal carcinoma of the prostate in needle
biopsy specimen. Most (82%) of the corresponding prostate cancers in the whole
gland were pathologically significant.
PMID- 9647593
TI - Prostatic carcinoma with signet ring cells: a clinicopathologic and
immunohistochemical analysis of 12 cases, with review of the literature.
AB - Prostatic adenocarcinoma with a signet ring cell (SRC) component is a rare,
incompletely characterized variant that must be distinguished from similar tumors
of bladder or gastric origin. In this study, we used mucin and immunoperoxidase
stains on formalin-fixed, paraffin-embedded sections from 12 prostatic
adenocarcinomas with SRC components, with antibodies to prostate-specific antigen
(PSA), cytokeratins, MIB-1, bcl-2, c-MET, CD44v6, and CD44v7; we performed a
comparison study on six bladder and seven gastric carcinomas with SRCs. The
prostatic SRC component was always associated with the usual high-grade
adenocarcinoma. Both components were positive for PSA, AE1/AE3, and CAM 5.2 (12
cases of 12) and also expressed c-MET (5 cases of 9), CD44v6 (9 of 10), and CDv7
(9 of 10). Only rare cells stained for bcl-2 (3 cases of 9). The mean MIB-1
proliferation index was 8%. Intracellular mucin was identified (periodic acid
Schiff with diastase predigestion (PAS-D) in 9 cases of 10, mucicarmine in 5 of
10, alcian blue in 6 of 10). Bladder and gastric tumors were positive for PSA (3
cases of 6 and 2 of 7, respectively), using a polyclonal antibody, and for bcl-2
(5 cases of 6, 2 of 7), c-MET (6 of 6, 6 of 7), CD44v6 (5 of 6, 6 of 7), and
CD44v7 (4 of 6, 4 of 7), with mean MIB-1 proliferation indices of 15 and 35%,
respectively. All were negative for cytokeratin 34 beta E12. We conclude that
prostatic adenocarcinomas with SRC components are typically accompanied by high
grade adenocarcinoma; are variably positive for mucin, with PAS-D being the most
sensitive stain; show expression of PSA, cytokeratins, MIB-1, bcl-2, c-MET, and
CD44 similar to that shown by high-grade adenocarcinoma components; have a low
MIB-1 proliferation index; and are not always distinguishable from SRC components
of bladder and stomach carcinomas with any of the above stains, including PSA.
PMID- 9647594
TI - Nonalcoholic fatty liver disease: assessment of variability in pathologic
interpretations.
AB - The exact cause, prevalence, and rate of progression of nonalcoholic fatty liver
disease (NAFLD) are unclear because of a lack of agreement on the pathologic
features associated with the different types of NAFLD, their clinical syndromes,
and because of a lack of accuracy in the interpretation of these pathologic
features. Studies of NAFLD would be aided by a consistent and standardized
approach to the interpretation of pathologic features. The aim of our study was
to assess interobserver and intraobserver variation in the histologic
abnormalities associated with NAFLD. We identified histologic features of NAFLD
as reported in the literature, and we identified patients with the diagnosis of
NAFLD through the databases of two large institutions. Histologic parameters were
evaluated for each liver biopsy specimen by four hepatopathologists and twice by
two of the four pathologists (blindly). Interobserver and intraobserver
concordance among the pathologists was measured by kappa statistics. Nineteen
histologic parameters compartmentalized into steatosis, inflammation, liver cell
injury, and fibrosis were evaluated on 53 liver biopsy specimens. Significant,
substantial, or moderate concordance was present in only six items: the extent of
steatosis, sinusoidal location of fibrosis, perivenular fibrosis, grade of
fibrosis, ballooning degeneration, and the presence of vacuolated nuclei.
Substantial or moderate concordance also was seen for interobserver readings for
location of steatosis and periportal injury. Parameters of inflammation were not
scored as reliably as parameters of fibrosis and cell injury. We conclude that
only some histologic features previously reported in NAFLD (especially those with
substantial and moderate concordance for both interobserver and intraobserver
interpretation) are interpreted uniformly by experienced pathologists. These
histologic features might prove useful for the development of a standardized and
reliable pathologic scoring system that includes the full histologic spectrum of
NAFLD and its various clinical outcomes.
PMID- 9647595
TI - Peripheral pulmonary adenocarcinomas with bronchioloalveolar features:
immunophenotypes correlate with histologic patterns.
AB - Peripheral pulmonary adenocarcinomas (PPAs) often demonstrate a
bronchioloalveolar component, with or without glandular differentiation. PPAs can
be nondescript, mucinous, or show features of Type II pneumocytes. Particularly,
mucinous lung carcinomas can resemble gastrointestinal metastases. Previous
reports suggested that patterns of keratins 7 (K7) and 20 (K20) differ in
pulmonary tumors versus enteric metastases. These studies, however, often failed
to specify the precise morphotypes of PPA. Thus, we undertook this evaluation of
PPAs with different histologic images. Thirty-nine cases were retrieved from
institutional files; all were confirmed as primary tumors by clinicopathologic
and radiographic review. Cases were classified as Type I (mucinous)
bronchioloalveolar carcinoma (BAC1); Type II (nonmucinous) bronchioloalveolar
carcinoma (BAC2); conventional PPA with BAC1-like areas (PPA1); or conventional
PPA with BAC2-like foci (PPA2). Immunostains were performed for K7, K20,
carcinoembryonic antigen, CA19-9, tumor-associated glycoprotein-72, surfactant
apoprotein-A, and the c-erbB-2 peptide. BAC1 and PPA1 failed to express
surfactant apoprotein-A, and BAC2 also consistently lacked K20, whereas 28% of
PPA2 lesions were labeled for K20. All of the other determinants, however, were
seen in variable proportions in each subgroup of PPA. Primary BAC1 and PPA1
resembled enteric adenocarcinomas immunophenotypically; on the other hand, BAC2
demonstrated a pattern of protein expression similar to that of Type II
pneumocytes. PPA2s are a diverse group of neoplasms, and a subset of PPA2 does
show K20 reactivity, as would be expected in metastatic enteric carcinomas. Thus,
immunohistochemical data on PPAs must be interpreted carefully and only in
clinicopathologic context. With respect specifically to primary pulmonary
mucinous tumors, there still seems to be no uniformly reliably marker that will
always allow the exclusion of metastatic enteric tumors.
PMID- 9647596
TI - Neurocristic cutaneous hamartoma: a distinctive dermal melanocytosis with an
unknown malignant potential.
AB - Neurocristic hamartomas (NCHs) result from aberrant development of the
neuromesenchyme. In addition to a dermal melanocytic component, these tumors can
contain neurosustentacular and fibrogenic components and can undergo malignant
transformation. Although NCHs have many features in common with other dermal
melanocytic neoplasms, including cellular blue nevi and some congenital nevi,
they have distinctive clinical and histologic features. We present a case report
of a 27-year-old white woman with an NCH of the scalp. The clinical, histologic,
and immunohistochemical features are compared with those of other dermal
melanocytic neoplasms. The NCH contained epithelioid pigmented melanocytes
positive for S-100 and HMB45, within which there were well-circumscribed nodules
of S-100+/Leu 7+/HMB45- cells surrounded by a capsule composed of spindle cells
positive for epithelial membrane antigen. The stromal cells throughout the tumor
were diffusely CD34 positive, and hair follicles were decreased and dystrophic
within the tumor. NCHs represent neoplastic dysplasia that involves not only
melanocytic cells but also neurosustentacular and fibrocytic effector cells. The
histologic and immunohistochemical features, along with the decreased and
dystrophic hair follicles, suggest that the abnormalities in the mesenchyme are
significant and result from the contribution of neural crest cells to the
cellular and matrix components of the mesenchyme.
PMID- 9647597
TI - Primary fibrosarcoma of the sella unrelated to previous radiation therapy.
AB - Fibrosarcomas involving the sella turcica are rare lesions and, when encountered,
have been associated with previous radiation of a pituitary adenoma. Although
primary intracranial fibrosarcomas are well recognized, no case of primary
fibrosarcoma of the sella turcica has been reported to date. We describe here a
patient who presented with a 2-month history of headache, visual disturbances,
and diabetes insipidus. Her past medical history was unremarkable, with no
radiation therapy. Magnetic resonance imaging revealed a sellar/suprasellar
lesion that at surgery appeared firm in consistency. A radical removal of the
mass was performed through a transsphenoidal approach. The patient recovered
promptly from the operation and 2 weeks later, given the aggressive histologic
appearance of the lesion, underwent gamma knife radiosurgery. Seven months after
diagnosis, the patient presented with local tumor recurrence. A subtotal surgical
resection was performed, and additional postsurgical treatment is still under
consideration. Although most often related to previous radiation of the pituitary
gland, primary fibrosarcomas can occur in the sella. This possibility should be
suspected in the differential diagnosis of sellar masses that lack the classical
characteristics of the much more common pituitary adenomas.
PMID- 9647598
TI - "Directoring" and managing in a professional system.
AB - Pathologists are under siege by corporate medicine, managed care systems, or
varieties of government-initiated health care restructuring. The pressure is on
us to attend at least equally to fiscal pressures, as well as to our patients'
medical needs. These pressures must be accommodated within the limits of our
professional duties and responsibilities. We must have more than an intuitive
sense of what it is to be a professional and to work in a system that is overseen
typically by a directorate and that includes managers and innovators. The example
of the failure of the corporate managers and directors of a national blood
transfusion service highlights the need to balance the inter-relationships of
managers, professionals, and innovators by a directorate knowledgeable in these
complex systems.
PMID- 9647599
TI - Correspondence re: Casey M, Rosenblatt R, Zimmerman J, Fineberg S. Mastectomy
without malignancy after carcinoma diagnosed by large-core stereotactic breast
biopsy. Mod Pathol 1997;10:1209-13.
PMID- 9647600
TI - Correspondence re: Sano T, Hikino T, Niwa Y, Kashiwabara K, Oyama T, Fukuda T,
Nakajima T. In situ hybridization with biotinylated tyramide amplification:
detection of human papillomavirus DNA in cervical neoplastic lesions. Mod Pathol
1998;11:19-23.
PMID- 9647601
TI - Leukotrienes and inflammation.
AB - Leukotrienes are potent pro-inflammatory mediators that appear to contribute to
pathophysiologic features of asthma. For example, cysteinyl leukotrienes contract
airway smooth muscle, increase microvascular permeability, stimulate mucus
secretion, decrease mucociliary clearance, and appear capable of recruiting
eosinophils into the airways. Segmental antigen bronchoprovocation in patients
with asthma increases LTC4 concentrations in bronchoalveolar lavage fluid, which
correlates with an influx of eosinophils into the airways. LTB4, in comparison,
selectively affects neutrophil functions. Intratracheal instillation of LTB4
produced a selective recruitment of neutrophils into the lung. These effects
suggest that leukotrienes contribute significantly to the inflammatory components
of asthma.
PMID- 9647602
TI - Pharmacology of leukotriene receptor antagonists.
AB - Preclinical pharmacological studies have demonstrated that cysLT, receptor
antagonists, such as zafirlukast, montelukast, and pobilukast, are potent and
selective antagonists of cysteinyl leukotriene (cysLT) activity. In vitro, these
agents compete with [3H]LTD4 for binding to cysLT, receptors present on guinea
pig and human lung cell membranes. Both zafirlukast and montelukast have
affinities that are approximately two times greater than that of the natural
ligand, LTD4. These agents block LTD4- and LTE4-induced contractions of isolated
guinea pig trachea, but do not antagonize LTC4-induced contractions, which are
putatively mediated by a different LT receptor, cysLT2. The cysLT2 receptor,
however, has not yet been found in human airway smooth muscle. In animal models,
these drugs inhibit LTD4-, LTE4-, and antigen-induced bronchoconstriction, reduce
inflammatory markers in models of pulmonary inflammation, and inhibit antigen
induced late-phase bronchoconstriction. This preclinical profile suggests that
cysLT, receptor antagonists may be useful in treating inflammatory conditions of
the respiratory system, such as asthma and allergic rhinitis.
PMID- 9647603
TI - Chemistry and structure--activity relationships of leukotriene receptor
antagonists.
AB - Several strategies have been employed by medicinal chemists in the design of
potent and selective leukotriene receptor antagonists-leukotriene structural
analogs, FPL 55712 analogs, and random screening of corporate compound banks.
Lead compounds were optimized, often through the exchange of ideas with groups
working on other chemical series of leukotriene antagonists. Pranlukast can
likely be traced to a lead compound identified by random screening that was
initially modified by incorporating structural components present in FPL 55712.
Montelukast originated from an early quinoline lead, which was modified with
leukotriene structural elements. Zafirlukast is based on a lead compound that
incorporated structural components from both FPL 55712 and the leukotrienes.
Therefore, each medicinal chemistry strategy that was originally employed has
successfully identified clinically effective leukotriene receptor antagonists.
PMID- 9647604
TI - Cell biology of the 5-lipoxygenase pathway.
AB - The initial enzymatic steps in leukotriene synthesis occur at the nuclear
envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to
selectively hydrolyze nuclear envelope phospholipids, releasing free
arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer
protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which
catalyzes a two-step reaction to produce leukotriene A4. In resting human and rat
peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat
basophilic leukemia cells and human alveolar macrophages, however, it is found
predominantly in the nucleus. Immunofluorescence microscopy studies demonstrate
that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following
cell activation. Many questions remain unanswered regarding the significance of
nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular
trafficking of these enzymes and their products.
PMID- 9647605
TI - Clinical pharmacology of leukotriene receptor antagonists and 5-lipoxygenase
inhibitors.
AB - Blinded, randomized, and placebo-controlled clinical trials have established that
cysteinyl leukotriene (cysLT) receptor antagonists and 5-lipoxygenase (5-LO)
inhibitors are safe and effective asthma treatments. Trials of 13- to 26-wks'
duration demonstrate that both the cysLT1 receptor antagonist, zafirlukast, and
the 5-LO inhibitor, zileuton, improve pulmonary function and decrease daytime and
nocturnal symptoms. Concomitant rescue beta-agonist inhaler use and the need for
corticosteroid rescue are also reduced. Preliminary studies suggest that
antileukotriene agents may also reduce indices of airway inflammation, including
inflammatory cell counts and airway hyperresponsiveness. Both cysLT1 antagonists
and 5-LO inhibitors offer a new approach to asthma management.
PMID- 9647606
TI - Summary of clinical trials with zafirlukast.
AB - Zafirlukast is an orally active and selective cysteinyl leukotriene (cysLT)
receptor antagonist. In humans, zafirlukast antagonized the effects of
exogenously administered LTD4 and cysLTs released endogenously in response to
physical and chemical stimuli. Zafirlukast antagonized LTD4-induced
bronchoconstriction, with effects still evident 12 h after drug administration.
In clinical models of asthma, zafirlukast inhibited bronchospasm after allergen
or exercise challenge in patients with asthma. In multicenter trials in patients
with chronic, stable asthma, zafirlukast reduced asthma symptoms, decreased as
needed beta-agonist use, and improved pulmonary function without increasing the
number of adverse events. Zafirlukast also exhibited evidence of an anti
inflammatory effect in the lung in preliminary studies involving segmental
antigen challenge. The results from these clinical trials demonstrate that
zafirlukast is effective and safe for the prophylactic treatment of asthma.
PMID- 9647607
TI - Basic and clinical aspects of myocardial stunning.
AB - Although the pathogenesis of myocardial stunning has not been definitively
established, the two major hypotheses are that it is caused by the generation of
oxygen-derived free radicals on reperfusion and by a loss of sensitivity of
contractile filaments to calcium. These hypotheses are not mutually exclusive and
are likely to represent different facets of the same pathophysiological cascade.
For example, a burst of free radical generation after reperfusion could alter
contractile filaments in a manner that renders them less responsive to calcium.
Increased free radical formation could also cause cellular calcium overload,
which would damage the contractile apparatus of the myocytes. There is now
considerable evidence that myocardial stunning occurs clinically in various
situations in which the heart is exposed to transient ischemia, such as unstable
angina, acute myocardial infarction with early reperfusion, exercise-induced
ischemia, cardiac surgery, and cardiac transplantation. Recognition of myocardial
stunning is clinically important and may impact patient treatment. Although no
ideal diagnostic technique for myocardial stunning has yet been developed,
thallium-201 scintigraphy or dobutamine echocardiography are available and can be
useful to identify viable myocardium with reversible wall motion abnormalities.
An intriguing possibility is that so-called chronic hibernation may in fact be
the result of repetitive episodes of stunning, which have a cumulative effect and
cause protracted postischemic left ventricular dysfunction. A better
understanding of myocardial stunning will expand our knowledge of the
pathophysiology of myocardial ischemia and provide a rationale for developing new
therapeutic strategies designed to prevent postischemic dysfunction.
PMID- 9647608
TI - Ischemic preconditioning: exploring the paradox.
AB - Brief transient episodes of nonlethal myocardial ischemia protect or
"precondition" the heart and render the myocardium resistant to a subsequent more
sustained ischemic insult. The hallmark of this phenomenon--documented in
virtually all species and experimental models evaluated to date in countless
laboratories worldwide--is the profound reduction in infarct size seen in
preconditioned groups versus time-matched controls. Efforts to identify the
cellular mechanisms responsible for this paradoxical ischemia-induced
cardioprotection, to expand the definition of ischemic preconditioning beyond
infarct size reduction, and, perhaps most importantly, to evaluate the efficacy
of preconditioning in disease models and in the clinical setting, are all topics
of intensive ongoing investigation.
PMID- 9647609
TI - Apoptosis in heart failure.
AB - A characteristic feature of heart failure is the progressive worsening of
ventricular function over months or years despite the absence of clinically
apparent intercurrent adverse events. The mechanism or mechanisms responsible for
this hemodynamic deterioration are not known but may be related to progressive
intrinsic contractile dysfunction of residual viable cardiac myocytes, or to
ongoing degeneration and loss of myocytes, or both. This report will address the
concept of ongoing cardiac myocyte loss that may occur during the course of
evolving heart failure viewed from the perspective of apoptosis or "programmed
cell death" as the potential mediator of cardiac muscle cell loss. In recent
years, several studies have shown that constituent myocytes of failed explanted
human hearts and hearts of animals with experimentally induced heart failure
undergo apoptosis. Recent studies have shown that cardiac myocyte apoptosis also
occurs after acute myocardial infarction, as well as in the hypertrophied heart
and the aging heart, conditions frequently associated with the development of
heart failure. Considerable work has also been conducted and novel concepts
advanced to explain potential molecular triggers of cardiac myocyte apoptosis in
heart failure. Although available data support the existence of myocyte apoptosis
in the failing heart, questions essential to our understanding of the importance
of myocyte apoptosis in this disease process remain unanswered. Lacking are
studies aimed at identifying physiological factors inherent to heart failure that
trigger myocyte apoptosis. Also lacking are studies that address the importance
of myocyte apoptosis in the progression of left ventricular dysfunction. If loss
of cardiac myocytes through apoptosis can be shown to be an important contributor
to the progression of heart failure, and if factors that trigger apoptosis in the
heart can be identified, such knowledge can potentially lead to the development
of novel therapeutic modalities aimed at preventing, or at the very least
retarding, the process of progressive ventricular dysfunction and the ultimate
transition toward end-stage, intractable heart failure.
PMID- 9647610
TI - Aortic pain.
AB - With the exception of the pain of acute aortic dissection, the thoracic aorta is
not usually considered as a pain-producing organ. However, nineteenth century
clinicians considered the aorta as a source of cardiovascular pain in the
presence of autopsy-documented inflammatory aortitis, aortic aneurysms, and
arterial hypertension, whereas early in the twentieth century, aortic pain
reactions were elicited in experimental studies involving distension of the
ascending aorta or the application of stimulating substances to the outer surface
of the aorta. More recently, increased attention to aortic elastic properties,
and to aortic vascular biology at the molecular level refocused interest on the
many facets of aortic function beyond that of a simple conduit. The recognition
of pain of thoracic aortic origin now extends to patients with progressive aortic
syndromes such as aortic intramural hematoma, aortic intimal tears, aortic
penetrating ulcers, aortic root dilatation without dissection in connective
tissue disorders, inflammatory aortopathies, and abnormalities of aortic
distensibility. The occurrence of pain during balloon inflation at balloon
angioplasty of aortic coarctation, which disappears immediately after deflation,
is the modern equivalent of the early experimental studies. The authors present a
consideration of thoracic aortic pain in light of contemporary concepts in
cardiovascular medicine with roots in the rich historical reservoir of
information about aortic function and disease.
PMID- 9647611
TI - Oxaliplatin (L-OHP): a new reality in colorectal cancer.
AB - Oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP) is a new platinum
derivative for the treatment of advanced colorectal cancer. Preclinical data have
shown that oxaliplatin is active in a wide range of human and murine tumour cell
lines, and has been found to be non-cross-resistant with cisplatin in various
cisplatin-resistant cell lines and tumours. Oxaliplatin in combination with 5
fluorouracil (5-FU) leads to synergistic antiproliferative activity both in vivo
and in vitro. Clinical data have shown that oxaliplatin is active and well
tolerated both as monotherapy and in combination with 5-FU/folinic acid in first-
or second-line treatment of patients with metastatic colorectal cancer.
Oxaliplatin has a very good safety profile, and studies have confirmed that
peripheral sensory neuropathy is related to the cumulative dose of oxaliplatin
administered and that this neuropathy is generally reversible after
discontinuation of treatment. High response rates and prolonged survival have
been achieved in metastatic colorectal cancer patients, even after 5-FU failure.
PMID- 9647612
TI - Oxaliplatin in practice.
AB - Oxaliplatin, a new third-generation platinum complex, is active in the treatment
of colorectal and advanced ovarian cancers, both as monotherapy and in
combination therapy. It has demonstrated a very good safety profile,
characterized by low haematotoxicity, and moderate and manageable
gastrointestinal toxicity. No significant renal or ototoxicities have been
observed. Oxaliplatin induces a peripheral sensory neuropathy which is
characterized by distal and perioral dysaesthesia, and is induced or exacerbated
by the cold; in general, it is regressive between cycles of treatment. This dose
limiting toxicity is cumulative, but reversible within a few months of
discontinuation of treatment in the majority of cases. In a cohort study of 490
patients with advanced colorectal cancer included in an extended access
programme, more than 2700 cycles of oxaliplatin plus 5-fluorouracil (5-FU) were
administered. The overall safety profile of oxaliplatin was shown to be very
favourable. Oxaliplatin and cisplatin, each in combination with cyclophosphamide,
have a similar efficacy in the treatment of advanced ovarian cancer, but
oxaliplatin was better tolerated than cisplatin in terms of haematological,
gastrointestinal, neurosensory and renal toxicities. The safety profile of
oxaliplatin makes it an ideal candidate for combination therapy.
PMID- 9647613
TI - Ongoing and unsaid on oxaliplatin: the hope.
AB - Oxaliplatin, the first available diaminocyclohexane platinum, has clinical
activity in colorectal and ovarian cancers. Its mechanism of action is thought to
be similar to that of cisplatin, its main mechanism being the intrastrand DNA
adduct between two adjacent guanins or two adjacent guanine and adenine adducts.
Ongoing molecular pharmacological studies of the mechanism of action of cisplatin
suggest that platinated adducts are recognized by proteins of the mismatch repair
system, including the products of the hMLH1 and hMSH2 genes. DNA mismatch repair
defects occur in a wide variety of sporadic human cancers, are the main genetic
factor in hereditary non-polyposis colon cancer and a frequent de novo or
acquired phenomenon in ovarian cancer and other solid tumours. Moreover, they
have recently been reported to be a cause of resistance to cisplatin but not to
oxaliplatin, as diaminocyclohexane platinum adducts do not appear to be
recognized by the mismatch repair complex. These findings explain the oxaliplatin
activity in some cisplatin-resistant tumours. In addition, the good safety
profile of oxaliplatin makes it a drug of choice for combination therapy, and it
has been shown to be synergistic with other cytotoxic agents, including 5
fluorouracil, cisplatin, carboplatin, topotecan, gemcitabine and CPT-11. The
results of several ongoing trials are awaited, but available data demonstrate
that oxaliplatin is highly effective in the treatment of advanced colorectal and
ovarian cancers. Promising early results suggest that it is also efficacious in
non-Hodgkin's lymphoma, breast and non-small-cell lung cancers. As a result of
its mechanism of action, its favourable safety profile and the differential
profile of its antitumoral activity, the full potential of oxaliplatin as an
active, versatile antitumoral agent is yet to be fully explored.
PMID- 9647614
TI - Exploiting tumour hypoxia and overcoming mutant p53 with tirapazamine.
AB - Human solid tumours are composed of a significant proportion of hypoxic cells,
i.e. cells with oxygen levels lower than those of normal tissues. Tumour hypoxic
cells have been shown to have a negative impact on the response of solid tumours
to radiation therapy and chemotherapy. However, these low cellular oxygen levels
can be exploited by a drug that is specifically activated to a cytotoxic
metabolite at these low levels. Tirapazamine is a novel bioreductive agent with
selective cytotoxicity to hypoxic tumour cells, irrespective of their p53 status
or apoptotic response, and acts synergistically with cisplatin. This potentiation
is dependent on an interaction that can only take place in a hypoxic environment,
resulting in a significant sensitization of the cells to cisplatin cell killing,
with no increase in the systemic toxicity of cisplatin. Thus, the low cellular
oxygen levels common in solid tumours can be turned from disadvantage to
advantage using the hypoxia-selective cytotoxic drug tirapazamine.
PMID- 9647615
TI - Tirapazamine-cisplatin: the synergy.
AB - Tirapazamine is a novel bioreductive agent with selective cytotoxicity against
hypoxic tumour cells. Synergy with cisplatin and other chemotherapeutic agents
has been shown in preclinical trials. Pharmacokinetic studies of tirapazamine
have revealed that exposure increases with dose over the range of 18-450 mg m(-2)
for a single dose and of 9-390 mg m(-2) for multiple doses. Plasma clearance is
high. Tirapazamine has been clinically tested in combination with cisplatin at
escalating doses in a phase I trial and at therapeutic doses in three separate
phase II trials in patients with advanced non-small-cell lung cancer (NSCLC) in
11 study centres. Limiting toxicity for tirapazamine at an intravenous dose of
390 mg m(-2) was acute, reversible hearing loss. Other frequently observed side
effects included muscle cramping and gastrointestinal symptoms. Tirapazamine did
not cause myelosuppression, and no toxic deaths were reported in these trials.
The anti-tumour efficacy against previously untreated, advanced NSCLC was
evaluated by cumulative intent-to-treat analysis of 132 patients. The objective
response rate (confirmed by two independent measurements) was 25% [confidence
interval (CI) 17.8-33.33], with a median survival of 38.9 weeks (CI 29.4-49.9).
The efficacy of tirapazamine plus cisplatin shown in these trials was better than
that of historical controls with cisplatin monotherapy. Two large-scale
international trials have been conducted, involving more than 70 centres, to
confirm these results. The CATAPULT I trial compares tirapazamine plus cisplatin
with cisplatin and has finished accrual with 446 patients. The CATAPULT II trial,
which is comparing tirapazamine plus cisplatin with etoposide plus cisplatin, had
enrolled 550 patients by June 1997. Follow-up is ongoing. Tirapazamine is the
promising first drug from a new class of cytotoxic agents with a novel mechanism
of action. It can be effectively combined with cisplatin, and possibly with other
agents, because of its safety profile and lack of overlapping dose-limiting
toxicity, such as myelosuppression. The combination of tirapazamine and cisplatin
appears to be safe and effective in the treatment of NSCLC.
PMID- 9647616
TI - Advances in the management of malignancy-associated hyperuricaemia.
AB - Acute tumour lysis syndrome (ATLS) is a metabolic derangement (hyperuricaemia,
hyperphosphataemia, hyperkalaemia and hypocalcaemia) associated with
lymphoproliferative malignancies. The nature and severity of the metabolic
alterations are variable. Major complications are oliguric acute renal failure
and delays in initiating chemotherapy. Current management of ATLS includes
hydration, alkalinization, diuretics, when indicated, and the reduction of uric
acid levels using allopurinol or urate oxidase. Allopurinol inhibits xanthine
oxidase, an enzyme that catalyses the conversion of hypoxanthine and xanthine to
uric acid. Urate oxidase (Uricozyme), a naturally occurring proteolytic enzyme in
many mammals, degrades uric acid to allantoins, which are ten times more soluble
than uric acid and easily eliminated by the kidneys. Recently, Sanofi Research
isolated a recombinant urate oxidase (SR29142) as a cDNA clone from Aspergillus
flavus, expressed in the yeast strain Saccharomyces cerevisiae. Preclinical
studies have documented its biological effects as a urolytic enzyme. Twenty-eight
healthy male volunteers received SR29142, and a rapid decline of uric acid below
measurable levels was seen within 4 h in all patients receiving a dose of more
than 0.10 mg kg(-1). Currently, SR29142 is undergoing clinical studies in both
Europe and the USA in patients with acute leukaemias or B-cell non-Hodgkin's
lymphoma to demonstrate its efficacy and safety in this population of patients at
highest risk of developing ATLS or its life-threatening sequelae.
PMID- 9647617
TI - [Experimental study on direct volume reconstruction].
AB - Application of DVR is investigated with the X-ray equipment under single circle
imaging geometry. A real volume model that consists of aluminum bar, lucite and
air bar is designed. A prototype imaging system that includes X-ray cone-beams
ource, rotating system, fluorescent screen, image intensifier, TV camera, image
acquisitor and microcomputer is constructed. The experimental results show that
DVR with the current simple X-ray equipment is of interests and values.
PMID- 9647618
TI - [The design of an OEM module-based hand-hold pulse oximeter].
AB - This paper describes the software and hardware design of an OEM module-based hand
hold pulse oximeter. The instrument has the features of compact structure,
reliable performance, having all the necessary functions, providing measurements
on any patients and low power consumption. It is possible to make this instrument
as a commercial product in shorter period.
PMID- 9647619
TI - [The development of a laser back-scattering erythrocyte-aggregometer].
AB - In this paper, an erythrocyte-aggregometer based on the analysis of the light
intensity back-scattered by a blood suspension is presented and described in
detail. It allows to approach aggregation phenomenon in terms of kinetics,
structural and rheological parameters. A personal computer and a microcomputer
are applied to automate the system's sampling, data-processing and data-restoring
procedure.
PMID- 9647620
TI - [A CR-self-adjusting data compression algorithm based on complex Fourier
transform].
AB - A CR-self-adjusting data compression algorithm based on complex Fourier transform
is presented in this paper. Because of the application of CFFT algorithm, the CR
is doulbled with high fidelity without the operations of QRS complex detection,
wave form analysis and difference calculation.
PMID- 9647621
TI - [The microcomputer controlling system of rotating gamma ray knife].
PMID- 9647622
TI - [A technique of PVC detection in QRS wave].
AB - A technique of PVC detection is described in this paper. The procedures of PVC
analysis include noise detection, QRS detection, feature extraction and QRS wave
classification. The interference is detected in hierarchy ways. A new non-linear
transformation of ECG waveform is given to be taken as the QRS detection
function. Taking this QRS detection function, the influence of noise and
interference can be reduced greatly. By the technique of QRS template matching,
QRS waveforms are sorted into different clusters in QRS wave form space. Then a
linear classifier is used to identify the medical meaning of these clustes.
Before the linear classifier is applied, the QRS waveforms are classified
according to some special decision rules. 38 half-hour standard database is used
to test the technique presented in this paper. The result shows t hat accuracy
rate of PVC detection is better than 95%.
PMID- 9647623
TI - [An instrument for estimating human body composition using impedance
measurement].
AB - According to the impedance feature of biological tissue, the instrument was
designed at 1, 5, 10, 50, 100kHz to measure human impedance, and then to
calculate human FAT, FFM, FAT%, TBW, ECW, ICW and so on. A 8031 singlechip
microprocessor contacuting used as a control center in the instrument. The part
of electric circuit contacuting human body in the instrument was unreally
earthing. The instrument was safty, effective, repeatable, and easily
manpulative. Prelimintary clinical experiment showed the results measured with
the instrument could effectively reflect practical, status of human composition.
PMID- 9647624
TI - [The research and application of uroflow rate measuring].
AB - Using A/D converter acquiring uroflowrate is introduced in this paper. The
uroflowrate curve is analysed and displayed by computer in real time. The
programming of uroflowrate curve smoothing is presented.
PMID- 9647625
TI - [The development of new-type soft X-ray tube].
AB - This report is based on the technology of image and photo-taking and the creative
mecaanism of X-ray. It also analyses the disadvanges of the outanode X-ray tube
and the limitations of its clinical practice. Moreover, it clarifies the
designing idea and the development result of a new-type soft X-ray tube.
PMID- 9647626
TI - [The development of a fluid percussion device for brain injury of animals].
AB - This paper discusses a fluid percussion device for brain injury. The injury is
produced by striking the cork with a pendulum dropped from a known fall height to
produce transient high pressure through a fluid transfer system. Experimental
results show the device has the advantages of making a controllable, repeatable,
and precise injury, and it can produce different levels of injury on different
animals.
PMID- 9647627
TI - [The development and application of the MJ-I electrode of stereo-location].
AB - We use the MJ-I electrode of stereo-location insert intrabrain to measure the
epileptic focus and to direct the surgical treating the patients with epilepsy.
Excellent operative results were achieved.
PMID- 9647628
TI - [Assessing indexes in the ECG data compression].
AB - This paper describes various numerical assessing indexes in evaluating algorithms
for the ECG data compression, such as numerical indexes of similarity (CC, RMS,
PRD), indexes of error (amplitude error, peak error), efficiency of compression
(Compression Ratio, bit rate), computing complexity, and so on. It also involves
visual inspection which is more important in assessing algorithms.
PMID- 9647629
TI - [ISFET transducer for clinical medicine application].
PMID- 9647630
TI - Random shotgun fire.
PMID- 9647631
TI - Odds on the FAST gene.
PMID- 9647632
TI - WebWise: guide to the University of Washington Genome Center web site.
PMID- 9647633
TI - Emerging patterns of comparative genome organization in some mammalian species as
revealed by Zoo-FISH.
AB - Although gene maps for a variety of evolutionarily diverged mammalian species
have expanded rapidly during the past few years, until recently it has been
difficult to precisely define chromosomal segments that are homologous between
species. A solution to this problem has come from the development of Zoo-FISH,
also known as cross-species chromosome painting. The use of Zoo-FISH to identify
regions of chromosomal homology has allowed the transfer of information from map
rich species such as human and mouse to a wide variety of other species. From a
Zoo-FISH analysis spanning four mammalian orders (Primates, Artiodactyla,
Carnivora, and Perissodactyla), and involving eight species (human, pig, cattle,
Indian muntjac, cat, American mink, harbor seal, and horse), three distinct
classes of synteny conservation have been designated: (1) conservation of whole
chromosome synteny, (2) conservation of large chromosomal blocks, and (3)
conservation of neighboring segment combinations. This analysis has also made it
possible to identify a set of chromosome segments (based on human chromosome
equivalents) that probably made up the karyotype of the common ancestor of the
four orders. This approach provides a basis for developing a picture of the
ancestral mammalian karyotype, but a full understanding will depend on studies
encompassing more diverse combinations of mammalian orders.
PMID- 9647634
TI - Large-scale taxonomic profiling of eukaryotic model organisms: a comparison of
orthologous proteins encoded by the human, fly, nematode, and yeast genomes.
AB - Comparisons of DNA and protein sequences between humans and model organisms,
including the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis
elegans, and the fruit fly Drosophila melanogaster, are a significant source of
information about the function of human genes and proteins in both normal and
disease states. Important questions regarding cross-species sequence comparison
remain unanswered, including (1) the fraction of the metabolic, signaling, and
regulatory pathways that is shared by humans and the various model organisms; and
(2) the validity of functional inferences based on sequence homology. We
addressed these questions by analyzing the available fractions of human, fly,
nematode, and yeast genomes for orthologous protein-coding genes, applying strict
criteria to distinguish between candidate orthologous and paralogous proteins.
Forty-two quartets of proteins could be identified as candidate orthologs. Twenty
four Drosophila protein sequences were more similar to their human orthologs than
the corresponding nematode proteins. Analysis of sequence substitutions and
evolutionary distances in this data set revealed that most C. elegans genes are
evolving more rapidly than Drosophila genes, suggesting that unequal evolutionary
rates may contribute to the differences in similarity to human protein sequences.
The available fraction of Drosophila proteins appears to lack representatives of
many protein families and domains, reflecting the relative paucity of genomic
data from this species.
PMID- 9647635
TI - Ribonuclease k6: chromosomal mapping and divergent rates of evolution within the
RNase A gene superfamily.
AB - We have localized the gene encoding human RNase k6 to within approximately 120 kb
on the long (q) arm of chromosome 14 by HAPPY mapping. With this information, the
relative positions of the six human RNase A ribonucleases that have been mapped
to this locus can be inferred. To further our understanding of the individual
lineages comprising the RNase A superfamily, we have isolated and characterized
10 novel genes orthologous to that encoding human RNase k6 from Great Ape, Old
World, and New World monkey genomes. Each gene encodes a complete ORF with no
less than 86% amino acid sequence identity to human RNase k6 with the eight
cysteines and catalytic histidines (H15 and H123) and lysine (K38) typically
observed among members of the RNase A superfamily. Interesting trends include an
unusually low number of synonymous substitutions (Ks) observed among the New
World monkey RNase k6 genes. When considering nonsilent mutations, RNase k6 is a
relatively stable lineage, with a nonsynonymous substitution rate of 0.40 x 10(
9) nonsynonymous substitutions/nonsynonymous site/year (ns/ns/yr). These results
stand in contrast to those determined for the primate orthologs of the two
closely related ribonucleases, the eosinophil-derived neurotoxin (EDN) and
eosinophil cationic protein (ECP), which have incorporated nonsilent mutations at
very rapid rates (1.9 x 10(-9) and 2.0 x 10(-9) ns/ns/yr, respectively). The
uneventful trends observed for RNase k6 serve to spotlight the unique nature of
EDN and ECP and the unusual evolutionary constraints to which these two
ribonuclease genes must be responding. [The sequence data described in this paper
have been submitted to the GenBank data library under accession nos. AF037081
AF037090.]
PMID- 9647636
TI - Evidence for the presence of insulin-dependent diabetes-associated alleles on the
distal part of mouse chromosome 6.
AB - Type 1 diabetes (IDDM) is a complex disorder with multifactorial and polygenic
etiology. A genome-wide screen performed in a BC1 cohort of a cross between the
nonobese diabetic (NOD) mouse with the diabetes-resistant feral strain PWK
detected a major locus contributing to diabetes development on the distal part of
chromosome 6. Unlike the majority of other Idd loci identified in intraspecific
crosses, susceptibility is associated with the presence of the PWK allele.
Genetic linkage analysis of congenic lines segregating PWK chromosome 6 segments
in a NOD background confirmed the presence of the Idd locus within this region.
The genetic interval defined by analysis of congenic animals showed a peak of
significant linkage (P = 0.0005) centered on an approximately 9-cM region lying
between D6Mit11 and D6Mit25 genetic markers within distal mouse chromosome 6.
[Genetic markers polymorphic between the NOD and PWK strains are available as a
supplement at http://www.genome.org]
PMID- 9647637
TI - Chicken microchromosomes are hyperacetylated, early replicating, and gene rich.
AB - The chicken karyotype consists of 39 chromosomes of which 33 are classed as
microchromosomes (MICs). MICs contain about one third of genomic DNA. The
majority of mapped chicken genes are assigned to macrochromosomes (MACs), but a
recent study indicated that CpG islands (CGIs), which are associated with most
vertebrate genes, map predominantly to MICs. The present work establishes that
chicken genes are concentrated on MICs by several criteria. Acetylated (lysine 5)
histone H4, which is strongly correlated with the presence of genes, is highly
enriched on MICs by immunocytochemistry. In addition, detailed analysis of
chicken cosmids shows that CGI-like fragments are approximately six times denser
on MICs than on MACs. Published mapping of randomly chosen genes by fluorescent
in situ hybridization (FISH) also shows a significant excess of microchromosomal
assignments. Finally, the finding that MICs replicate during the first half of S
phase is also compatible with the suggestion that MICs represent gene-rich DNA.
We use the cosmid data to predict that approximately 75% of chicken genes are
located on microchromosomes. [The sequence data described in this paper have been
submitted to the GenBank data library under accession nos. AJ001643 and
AJ001644.]
PMID- 9647638
TI - Physical map of human 6p21.2-6p21.3: region flanking the centromeric end of the
major histocompatibility complex.
AB - We have physically mapped and cloned a 2.5-Mb chromosomal segment flanking the
centromeric end of the major histocompatibility complex (MHC). We characterized
in detail 27 YACs, 144 cosmids, 51 PACs, and 5 BACs, which will facilitate the
complete genomic sequencing of this region of chromosome 6. The contig contains
the genes encoding CSBP, p21, HSU09564 serine kinase, ZNF76, TCP-11, RPS10,
HMGI(Y), BAK, and the human homolog of Tctex-7 (HSET). The GLO1 gene was mapped
further centromeric in the 6p21.2-6p21.1 region toward TCTE-1. The gene order of
the GLO1-HMGI(Y) segment in respect to the centromere is similar to the gene
order in the mouse t-chromosome distal inversion, indicating that there is
conservation in gene content but not gene order between humans and mice in this
region. The close linkage of the BAK and CSBP genes to the MHC is of interest
because of their possible involvement in autoimmune disease.
PMID- 9647639
TI - A software system for data analysis in automated DNA sequencing.
AB - Software for gel image analysis and base-calling in fluorescence-based sequencing
consisting of two primary programs, BaseFinder and GelImager, is described.
BaseFinder is a framework for trace processing, analysis, and base-calling.
BaseFinder is highly extensible, allowing the addition of trace analysis and
processing modules without recompilation. Powerful scripting capabilities
combined with modularity and multilane handling allow the user to customize
BaseFinder to virtually any type of trace processing. We have developed an
extensive set of data processing and analysis modules for use with the program in
fluorescence-based sequencing. GelImager is a framework for gel image
manipulation. It can be used for gel visualization, lane retracking, and as a
front end to the Washington University Getlanes program. The programs were
designed using a cross-platform development environment, currently allowing them
to run in Windows NT, Windows 95, Openstep/Mach, and Rhapsody. Work is ongoing to
deploy the software on additional platforms, including Solaris, Linux, and MacOS.
This software has been thoroughly tested and debugged in the analysis of >2
million bp of raw sequence data from human chromosome 19 region q13. Overall
sequencing accuracy was measured using a significant subset of these data,
consisting of approximately 600 sequences, by comparing the individual shotgun
sequences against the final assembled contigs. Also, results are reported from
experiments that analyzed the accuracy of the software and two other well-known
base-calling programs for sequencing the M13mp18 vector sequence. [The sequence
data described in this paper have been submitted to the GenBank data library
under accession no. AF025422]
PMID- 9647640
TI - Rescue of targeted regions of mammalian chromosomes by in vivo recombination in
yeast.
AB - In contrast to other animal cell lines, the chicken pre-B cell lymphoma line,
DT40, exhibits a high level of homologous recombination, which can be exploited
to generate site-specific alterations in defined target genes or regions. In
addition, the ability to generate human/chicken monochromosomal hybrids in the
DT40 cell line opens a way for specific targeting of human genes. Here we
describe a new strategy for direct isolation of a human chromosomal region that
is based on targeting of the chromosome with a vector containing a yeast
selectable marker, centromere, and an ARS element. This procedure allows rescue
of the targeted region by transfection of total genomic DNA into yeast
spheroplasts. Selection for the yeast marker results in isolation of chromosome
sequences in the form of large circular yeast artificial chromosomes (YACs) up to
170 kb in size containing the targeted region. These YACs are generated by
homologous recombination in yeast between common repeated sequences in the
targeted chromosomal fragment. Alternatively, the targeted region can be rescued
as a linear YACs when a YAC fragmentation vector is included in the yeast
transformation mixture. Because the entire isolation procedure of the chromosomal
region, once a target insertion is obtained, can be accomplished in approximately
1 week, the new method greatly expands the utility of the homologous
recombinationproficient DT40 chicken cell system.
PMID- 9647641
TI - Vector-hexamer PCR isolation of all insert ends from a YAC contig of the mouse
Igh locus.
AB - We have developed a simple PCR strategy, termed vector-hexamer PCR, that is
unique in its ability to easily recover every insert end from large insert clones
in YAC and BAC vectors. We used this method to amplify and isolate all insert
ends from a YAC contig covering the mouse Igh locus. Seventy-seven ends were
amplified and sequenced from 36 YAC clones from four libraries in the pYAC4
vector. Unexpectedly, 40% of the insert ends of these YACs were LINE1 repeats.
Nonrepetitive ends were suitable for use as probes on Southern blots of digested
YACs to identify overlaps and construct a contig. The same strategy was used
successfully to amplify insert ends from YACs in the pRML vector from the
Whitehead Institute/MIT-820 mouse YAC library and from BACs in pBeloBAC11. The
simplicity of this technique and its ability to isolate every end from large
insert clones are of great utility in genomic investigation. [The nucleotide
sequence data reported in this paper are accessible in GenBank under accession
nos. B07512-B07598.]
PMID- 9647642
TI - Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits
alphavirus-induced apoptosis.
AB - Recent studies have established cell type- specific, proapoptotic, or
antiapoptotic functions for the transcription factor NF-kappaB. In each of these
studies, inhibitors of NF-kappaB activity have been present before the apoptotic
stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing
or inhibiting survival could not be directly assessed. Sindbis virus, an
alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To
address whether Sindbis virus- induced NF-kappaB activation is required for
apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF
kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither
prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition
of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis.
Our results demonstrate that suppression of steady-state, but not stimulus
induced NF-kappaB activity, regulates expression of gene products required for
Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF
kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We
propose that the role of NF-kappaB in regulating apoptosis is determined by the
death stimulus and by the timing of modulating NF-kappaB activity relative to the
death stimulus.
PMID- 9647643
TI - Localization, dynamics, and protein interactions reveal distinct roles for ER and
Golgi SNAREs.
AB - ER-to-Golgi transport, and perhaps intraGolgi transport involves a set of
interacting soluble N-ethylmaleimide-sensitive factor attachment protein receptor
(SNARE) proteins including syntaxin 5, GOS-28, membrin, rsec22b, and rbet1. By
immunoelectron microscopy we find that rsec22b and rbet1 are enriched in COPII
coated vesicles that bud from the ER and presumably fuse with nearby vesicular
tubular clusters (VTCs). However, all of the SNAREs were found on both COPII- and
COPI-coated membranes, indicating that similar SNARE machinery directs both
vesicle pathways. rsec22b and rbet1 do not appear beyond the first Golgi
cisterna, whereas syntaxin 5 and membrin penetrate deeply into the Golgi stacks.
Temperature shifts reveal that membrin, rsec22b, rbet1, and syntaxin 5 are
present together on membranes that rapidly recycle between peripheral and Golgi
centric locations. GOS-28, on the other hand, maintains a fixed localization in
the Golgi. By immunoprecipitation analysis, syntaxin 5 exists in at least two
major subcomplexes: one containing syntaxin 5 (34-kD isoform) and GOS-28, and
another containing syntaxin 5 (41- and 34-kD isoforms), membrin, rsec22b, and
rbet1. Both subcomplexes appear to involve direct interactions of each SNARE with
syntaxin 5. Our results indicate a central role for complexes among rbet1,
rsec22b, membrin, and syntaxin 5 (34 and 41 kD) at two membrane fusion
interfaces: the fusion of ER-derived vesicles with VTCs, and the assembly of VTCs
to form cis-Golgi elements. The 34-kD syntaxin 5 isoform, membrin, and GOS-28 may
function in intraGolgi transport.
PMID- 9647644
TI - The SNARE machinery is involved in apical plasma membrane trafficking in MDCK
cells.
AB - We have investigated the controversial involvement of components of the SNARE
(soluble N-ethyl maleimide-sensitive factor [NSF] attachment protein [SNAP]
receptor) machinery in membrane traffic to the apical plasma membrane of
polarized epithelial (MDCK) cells. Overexpression of syntaxin 3, but not of
syntaxins 2 or 4, caused an inhibition of TGN to apical transport and apical
recycling, and leads to an accumulation of small vesicles underneath the apical
plasma membrane. All other tested transport steps were unaffected by syntaxin 3
overexpression. Botulinum neurotoxin E, which cleaves SNAP-23, and antibodies
against alpha-SNAP inhibit both TGN to apical and basolateral transport in a
reconstituted in vitro system. In contrast, we find no evidence for an
involvement of N-ethyl maleimide-sensitive factor in TGN to apical transport,
whereas basolateral transport is NSF-dependent. We conclude that syntaxin 3, SNAP
23, and alpha-SNAP are involved in apical membrane fusion. These results
demonstrate that vesicle fusion with the apical plasma membrane does not use a
mechanism that is entirely unrelated to other cellular membrane fusion events,
but uses isoforms of components of the SNARE machinery, which suggests that they
play a role in providing specificity to polarized membrane traffic.
PMID- 9647645
TI - The mammalian calcium-binding protein, nucleobindin (CALNUC), is a Golgi resident
protein.
AB - We have identified CALNUC, an EF-hand, Ca2+-binding protein, as a Golgi resident
protein. CALNUC corresponds to a previously identified EF-hand/calcium-binding
protein known as nucleobindin. CALNUC interacts with Galphai3 subunits in the
yeast two-hybrid system and in GST-CALNUC pull-down assays. Analysis of deletion
mutants demonstrated that the EF-hand and intervening acidic regions are the site
of CALNUC's interaction with Galphai3. CALNUC is found in both cytosolic and
membrane fractions. The membrane pool is tightly associated with the luminal
surface of Golgi membranes. CALNUC is widely expressed, as it is detected by
immunofluorescence in the Golgi region of all tissues and cell lines examined. By
immunoelectron microscopy, CALNUC is localized to cis-Golgi cisternae and the cis
Golgi network (CGN). CALNUC is the major Ca2+-binding protein detected by 45Ca2+
binding assay on Golgi fractions. The properties of CALNUC and its high homology
to calreticulin suggest that it may play a key role in calcium homeostasis in the
CGN and cis-Golgi cisternae.
PMID- 9647646
TI - G protein beta subunit-null mutants are impaired in phagocytosis and chemotaxis
due to inappropriate regulation of the actin cytoskeleton.
AB - Chemotaxis and phagocytosis are basically similar in cells of the immune system
and in Dictyostelium amebae. Deletion of the unique G protein beta subunit in D.
discoideum impaired phagocytosis but had little effect on fluid-phase
endocytosis, cytokinesis, or random motility. Constitutive expression of wild
type beta subunit restored phagocytosis and normal development. Chemoattractants
released by cells or bacteria trigger typical transient actin polymerization
responses in wild-type cells. In beta subunit-null cells, and in a series of beta
subunit point mutants, these responses were impaired to a degree that correlated
with the defect in phagocytosis. Image analysis of green fluorescent protein
actin transfected cells showed that beta subunit- null cells were defective in
reshaping the actin network into a phagocytic cup, and eventually a phagosome, in
response to particle attachment. Our results indicate that signaling through
heterotrimeric G proteins is required for regulating the actin cytoskeleton
during phagocytic uptake, as previously shown for chemotaxis. Inhibitors of
phospholipase C and intracellular Ca2+ mobilization inhibited phagocytosis,
suggesting the possible involvement of these effectors in the process.
PMID- 9647647
TI - Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions
with no sequence similarity to occludin.
AB - Occludin is the only known integral membrane protein localizing at tight
junctions (TJ), but recent targeted disruption analysis of the occludin gene
indicated the existence of as yet unidentified integral membrane proteins in TJ.
We therefore re-examined the isolated junction fraction from chicken liver, from
which occludin was first identified. Among numerous components of this fraction,
only a broad silver-stained band approximately 22 kD was detected with the
occludin band through 4 M guanidine-HCl extraction as well as sonication followed
by stepwise sucrose density gradient centrifugation. Two distinct peptide
sequences were obtained from the lower and upper halves of the broad band, and
similarity searches of databases allowed us to isolate two full-length cDNAs
encoding related mouse 22-kD proteins consisting of 211 and 230 amino acids,
respectively. Hydrophilicity analysis suggested that both bore four transmembrane
domains, although they did not show any sequence similarity to occludin.
Immunofluorescence and immunoelectron microscopy revealed that both proteins
tagged with FLAG or GFP were targeted to and incorporated into the TJ strand
itself. We designated them as "claudin-1" and "claudin-2", respectively. Although
the precise structure/function relationship of the claudins to TJ still remains
elusive, these findings indicated that multiple integral membrane proteins with
four putative transmembrane domains, occludin and claudins, constitute TJ
strands.
PMID- 9647648
TI - Mechanical fluctuations of the membrane-skeleton are dependent on F-actin ATPase
in human erythrocytes.
AB - Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark
field microscopy, were shown to depend, to a large extent, on intracellular MgATP
(Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study
extends that investigation and associates CMF with F-actin's ATPase activity.
MgATP was found to reconstitute CMF in red blood cell (RBC) ghosts and RBC
skeletons to their levels in intact RBCs, with an apparent Kd of 0.29 mM.
However, neither non-hydrolyzable ATP analogues (AMP-PNP, ATPgammaS) nor
hydrolyzable ones (ITP, GTP), were able to elevate CMF levels. The inhibition of
ATPase activity associated with the RBC's skeleton, carried out either by the
omission of the MgATP substrate or by the use of several inhibitors (vanadate,
phalloidin, and DNase I), resulted in a strong decrease of CMF. We suggest that
the actin's ATPase, located at the pointed end of the short actin filament, is
responsible for the MgATP stimulation of CMF in RBCs.
PMID- 9647649
TI - C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the
cell cycle-regulated protein kinase Nek2.
AB - Nek2 (for NIMA-related kinase 2) is a mammalian cell cycle-regulated kinase
structurally related to the mitotic regulator NIMA of Aspergillus nidulans. In
human cells, Nek2 associates with centrosomes, and overexpression of active Nek2
has drastic consequences for centrosome structure. Here, we describe the
molecular characterization of a novel human centrosomal protein, C-Nap1 (for
centrosomal Nek2-associated protein 1), first identified as a Nek2-interacting
protein in a yeast two-hybrid screen. Antibodies raised against recombinant C
Nap1 produced strong labeling of centrosomes by immunofluorescence, and
immunoelectron microscopy revealed that C-Nap1 is associated specifically with
the proximal ends of both mother and daughter centrioles. On Western blots, anti
C-Nap1 antibodies recognized a large protein (>250 kD) that was highly enriched
in centrosome preparations. Sequencing of overlapping cDNAs showed that C-Nap1
has a calculated molecular mass of 281 kD and comprises extended domains of
predicted coiled-coil structure. Whereas C-Nap1 was concentrated at centrosomes
in all interphase cells, immunoreactivity at mitotic spindle poles was strongly
diminished. Finally, the COOH-terminal domain of C-Nap1 could readily be
phosphorylated by Nek2 in vitro, as well as after coexpression of the two
proteins in vivo. Based on these findings, we propose a model implicating both
Nek2 and C-Nap1 in the regulation of centriole-centriole cohesion during the cell
cycle.
PMID- 9647650
TI - A role for NIMA in the nuclear localization of cyclin B in Aspergillus nidulans.
AB - NIMA promotes entry into mitosis in late G2 by some mechanism that is after
activation of the Aspergillus nidulans G2 cyclin-dependent kinase,
NIMXCDC2/NIMECyclin B. Here we present two independent lines of evidence which
indicate that this mechanism involves control of NIMXCDC2/NIMECyclin B
localization. First, we found that NIMECyclin B localized to the nucleus and the
nucleus-associated organelle, the spindle pole body, in a NIMA-dependent manner.
Analysis of cells from asynchronous cultures, synchronous cultures, and cultures
arrested in S or G2 showed that NIMECyclin B was predominantly nuclear during
interphase, with maximal nuclear accumulation in late G2. NIMXCDC2 colocalized
with NIMECyclin B in G2 cells. Although inactivation of NIMA using either the
nimA1 or nimA5 temperature-sensitive mutations blocked cells in G2,
NIMXCDC2/NIMECyclin B localization was predominantly cytoplasmic rather than
nuclear. Second, we found that nimA interacts genetically with sonA, which is a
homologue of the yeast nucleocytoplasmic transporter GLE2/RAE1. Mutations in sonA
were identified as allele-specific suppressors of nimA1. The sonA1 suppressor
alleviated the nuclear division and NIMECyclin B localization defects of nimA1
cells without markedly increasing NIMXCDC2 or NIMA kinase activity. These results
indicate that NIMA promotes the nuclear localization of the NIMXCDC2/ NIMECyclin
B complex, by a process involving SONA. This mechanism may be involved in
coordinating the functions of NIMXCDC2 and NIMA in the regulation of mitosis.
PMID- 9647651
TI - Structural analysis of Drosophila merlin reveals functional domains important for
growth control and subcellular localization.
AB - Merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene,
is a member of the protein 4.1 superfamily that is most closely related to ezrin,
radixin, and moesin (ERM). NF2 is a dominantly inherited disease characterized by
the formation of bilateral acoustic schwannomas and other benign tumors
associated with the central nervous system. To understand its cellular functions,
we are studying a Merlin homologue in Drosophila. As is the case for NF2 tumors,
Drosophila cells lacking Merlin function overproliferate relative to their
neighbors. Using in vitro mutagenesis, we define functional domains within Merlin
required for proper subcellular localization and for genetic rescue of lethal
Merlin alleles. Remarkably, the results of these experiments demonstrate that all
essential genetic functions reside in the plasma membrane- associated NH2
terminal 350 amino acids of Merlin. Removal of a seven-amino acid conserved
sequence within this domain results in a dominant-negative form of Merlin that is
stably associated with the plasma membrane and causes overproliferation when
expressed ectopically in the wing. In addition, we provide evidence that the COOH
terminal region of Merlin has a negative regulatory role, as has been shown for
ERM proteins. These results provide insights into the functions and functional
organization of a novel tumor suppressor gene.
PMID- 9647652
TI - Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in
culture.
AB - Several neuronal RNAs have been identified in dendrites, and it has been
suggested that the dendritic location of these RNAs may be relevant to the
spatiotemporal regulation of mosaic postsynaptic protein repertoires through
transsynaptic activity. Such regulation would require that dendritic RNAs
themselves, or at least some of them, be subject to physiological control. We
have therefore examined the functional regulation of somatodendritic expression
levels of dendritic BC1 RNA in hippocampal neurons in culture. BC1 RNA, an RNA
polymerase III transcript that is a component of a ribonucleoprotein particle,
became first detectable in somatodendritic domains of developing hippocampal
neurons at times of initial synapse formation. BC1 RNA was identified only in
such neurons that had established synapses on cell bodies and/or developing
dendritic arbors. When synaptic contact formation was initiated later in low
density cultures, BC1 expression was coordinately delayed. Inhibition of neuronal
activity in hippocampal neurons resulted in a substantial but reversible
reduction of somatodendritic BC1 expression. We conclude that expression of BC1
RNA in somatic and dendritic domains of hippocampal neurons is regulated in
development, and is dependent upon neuronal activity. These results establish
(for the first time to our knowledge) that an RNA polymerase III transcript can
be subject to control through physiological activity in nerve cells.
PMID- 9647653
TI - A role of tyrosine phosphatase in acetylcholine receptor cluster dispersal and
formation.
AB - Innervation of the skeletal muscle involves local signaling, leading to
acetylcholine receptor (AChR) clustering, and global signaling, manifested by the
dispersal of preexisting AChR clusters (hot spots). Receptor tyrosine kinase
(RTK) activation has been shown to mediate AChR clustering. In this study, the
role of tyrosine phosphatase (PTPase) in the dispersal of hot spots was examined.
Hot spot dispersal in cultured Xenopus muscle cells was initiated immediately
upon the presentation of growth factor-coated beads that induce both AChR cluster
formation and dispersal. Whereas the density of AChRs decreased with time, the
fine structure of the hot spot remained relatively constant. Although AChR,
rapsyn, and phosphotyrosine disappeared, a large part of the original hot spot
associated cytoskeleton remained. This suggests that the dispersal involves the
removal of a key linkage between the receptor and its cytoskeletal
infrastructure. The rate of hot spot dispersal is inversely related to its
distance from the site of synaptic stimulation, implicating the diffusible nature
of the signal. PTPase inhibitors, such as pervanadate or phenylarsine oxide,
inhibited hot spot dispersal. In addition, they also affected the formation of
new clusters in such a way that AChR microclusters extended beyond the boundary
set by the clustering stimuli. Furthermore, by introducing a constitutively
active PTPase into cultured muscle cells, hot spots were dispersed in a stimulus-
independent fashion. This effect of exogenous PTPase was also blocked by
pervanadate. These results implicate a role of PTPase in AChR cluster dispersal
and formation. In addition to RTK activation, synaptic stimulation may also
activate PTPase which acts globally to destabilize preexisting AChR hot spots and
locally to facilitate AChR clustering in a spatially discrete manner by
countering the action of RTKs.
PMID- 9647654
TI - Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated
neurite remodeling in neuroblastoma N1E-115 cells.
AB - A critical role for the small GTPase Rho and one of its targets, p160ROCK (a Rho
associated coiled coil-forming protein kinase), in neurite remodeling was
examined in neuroblastoma N1E-115 cells. Using wild-type and a dominant-negative
form of p160ROCK and a p160ROCK-specific inhibitor, Y-27632, we show here that
p160ROCK activation is necessary and sufficient for the agonist-induced neurite
retraction and cell rounding. The neurite retraction was accompanied by elevated
phosphorylation of myosin light chain and the disassembly of the intermediate
filaments and microtubules. Y-27632 blocked both neurite retraction and the
elevation of myosin light chain phosphorylation in a similar concentration
dependent manner. On the other hand, suppression of p160ROCK activity by
expression of a dominant-negative form of p160ROCK induced neurites in the
presence of serum by inducing the reassembly of the intermediate filaments and
microtubules. The neurite outgrowth by the p160ROCK inhibition was blocked by
coexpression of dominant-negative forms of Cdc42 and Rac, indicating that
p160ROCK constitutively and negatively regulates neurite formation at least in
part by inhibiting activation of Cdc42 and Rac. The assembly of microtubules and
intermediate filaments to form extended processes by inhibitors of the Rho-ROCK
pathway was also observed in Swiss 3T3 cells. These results indicate that
Rho/ROCK-dependent tonic inhibition of cell process extension is exerted via
activation of the actomysin-based contractility, in conjunction with a
suppression of assembly of intermediate filaments and microtubules in many cell
types including, but not exclusive to, neuronal cells.
PMID- 9647655
TI - Src family tyrosine kinase regulates intracellular pH in cardiomyocytes.
AB - The Anion Cl-/HCO3- Exchangers AE1, AE2, and AE3 are membrane pH regulatory ion
transporters ubiquitously expressed in vertebrate tissues. Besides relieving
intracellular alkaline and CO2 loads, the AEs have an important function during
development and cell death and play a central role in such cellular properties as
cell shape, metabolism, and contractility. The activity of AE(s) are regulated by
neurohormones. However, little is known as to the intracellular signal
transduction pathways that underlie this modulation. We show here that, in
cardiomyocytes that express both AE1 and AE3, the purinergic agonist, ATP,
triggers activation of anion exchange. The AE activation is observed in cells in
which AE3 expression was blocked but not in cells microinjected with neutralizing
anti-AE1 antibodies. ATP induces tyrosine phosphorylation of AE1, activation of
the tyrosine kinase Fyn, and association of both Fyn and FAK with AE1. Inhibition
of Src family kinases in vivo by genistein, herbimycin A, or ST638 prevents
purinergic activation of AE1. Microinjection of either anti-Cst.1 antibody or
recombinant CSK, both of which prevent activation of Src family kinase,
significantly decreases ATP-induced activation of AE. Microinjection of an anti
FAK antibody as well as expression in cardiomyocytes of Phe397 FAK dominant
negative mutant, also prevents purinergic activation of AE. Therefore, tyrosine
kinases play a key role in acute regulation of intracellular pH and thus in cell
function including excitation-contraction coupling of the myocardium.
PMID- 9647656
TI - Activation of the MAP kinase pathway by FGF-1 correlates with cell proliferation
induction while activation of the Src pathway correlates with migration.
AB - FGF regulates both cell migration and proliferation by receptor-dependent
induction of immediate-early gene expression and tyrosine phosphorylation of
intracellular polypeptides. Because little is known about the disparate nature of
intracellular signaling pathways, which are able to discriminate between cell
migration and proliferation, we used a washout strategy to examine the
relationship between immediate-early gene expression and tyrosine phosphorylation
with respect to the potential of cells either to migrate or to initiate DNA
synthesis in response to FGF-1. We demonstrate that transient exposure to FGF-1
results in a significant decrease in Fos transcript expression and a decrease in
tyrosine phosphorylation of the FGFR-1, p42(mapk), and p44(mapk). Consistent with
these biochemical effects, we demonstrate that attenuation in the level of DNA
synthesis such that a 1.5-h withdrawal is sufficient to return the population to
a state similar to quiescence. In contrast, the level of Myc mRNA, the activity
of Src, the tyrosine phosphorylation of cortactin, and the FGF-1-induced
redistribution of cortactin and F-actin were unaffected by transient FGF-1
stimulation. These biochemical responses are consistent with an implied
uncompromised migratory potential of the cells in response to growth factor
withdrawal. These results suggest a correlation between Fos expression and the
mitogen-activated protein kinase pathway with initiation of DNA synthesis and a
correlation between high levels of Myc mRNA and Src kinase activity with the
regulation of cell migration.
PMID- 9647657
TI - Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor
(VEGF) expression in the endothelial cells of forming capillaries: an autocrine
mechanism contributing to angiogenesis.
AB - FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we
show that FGF-2 induces VEGF expression in vascular endothelial cells through
autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured
endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF
expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2-induced
endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates
VEGF expression through extracellular interaction with cell membrane receptors;
high-Mr FGF-2 (22-24-kD) acts via intracellular mechanism(s). During angiogenesis
induced by FGF-2 in the mouse cornea, the endothelial cells of forming
capillaries express VEGF mRNA and protein. Systemic administration of
neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis.
Because occasional fibroblasts or other cell types present in the corneal stroma
show no significant expression of VEGF mRNA, these findings demonstrate that
endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced
angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism
that involves the autocrine action of vascular endothelial cell-derived FGF-2 and
VEGF.
PMID- 9647658
TI - The laminin-nidogen complex is a ligand for a specific splice isoform of the
transmembrane protein tyrosine phosphatase LAR.
AB - Leukocyte antigen-related protein (LAR) is a prototype for a family of
transmembrane protein tyrosine phosphatases whose extracellular domain is
composed of three Ig and several fibronectin type III (FnIII) domains. Complex
alternative splicing of the LAR-FnIII domains 4-8 has been observed. The
extracellular matrix laminin-nidogen complex was identified as a ligand for the
LAR-FnIII domain 5 (Fn5) using a series of GST-LAR-FnIII domain fusion proteins
and testing them in in vitro ligand-binding assays. LAR- laminin-nidogen binding
was regulated by alternative splicing of a small exon within the LAR-Fn5 so that
inclusion of this exon sequence resulted in disruption of the laminin-nidogen
binding activity. Long cellular processes were observed when HeLa cells were
plated on laminin-nidogen, but not when plated on a fibronectin surface. Indirect
immunofluorescent antibody staining revealed high expression of LAR in a punctate
pattern, throughout the length of these cellular processes observed on laminin
nidogen. Antibody-induced cross-linking of LAR inhibited formation of these
cellular processes, and inhibition was correlated with changes in cellular actin
cytoskeletal structure. Thus, LAR-laminin-nidogen binding may play a role in
regulating cell signaling induced by laminin-nidogen, resulting in cell
morphological changes.
PMID- 9647659
TI - Complementary roles for receptor clustering and conformational change in the
adhesive and signaling functions of integrin alphaIIb beta3.
AB - Integrin alphaIIb beta3 mediates platelet aggregation and "outside-in" signaling.
It is regulated by changes in receptor conformation and affinity and/or by
lateral diffusion and receptor clustering. To document the relative contributions
of conformation and clustering to alphaIIb beta3 function, alphaIIb was fused at
its cytoplasmic tail to one or two FKBP12 repeats (FKBP). These modified alphaIIb
subunits were expressed with beta3 in CHO cells, and the heterodimers could be
clustered into morphologically detectable oligomers upon addition of AP1510, a
membrane-permeable, bivalent FKBP ligand. Integrin clustering by AP1510 caused
binding of fibrinogen and a multivalent (but not monovalent) fibrinogen-mimetic
antibody. However, ligand binding due to clustering was only 25-50% of that
observed when alphaIIb beta3 affinity was increased by an activating antibody or
an activating mutation. The effects of integrin clustering and affinity
modulation were additive, and clustering promoted irreversible ligand binding.
Clustering of alphaIIb beta3 also promoted cell adhesion to fibrinogen or von
Willebrand factor, but not as effectively as affinity modulation. However,
clustering was sufficient to trigger fibrinogen-independent tyrosine
phosphorylation of pp72(Syk) and fibrinogen-dependent phosphorylation of
pp125(FAK), even in non-adherent cells. Thus, receptor clustering and affinity
modulation play complementary roles in alphaIIb beta3 function. Affinity
modulation is the predominant regulator of ligand binding and cell adhesion, but
clustering increases these responses further and triggers protein tyrosine
phosphorylation, even in the absence of affinity modulation. Both affinity
modulation and clustering may be needed for optimal function of alphaIIb beta3 in
platelets.
PMID- 9647660
TI - Xanthine oxidase reaction with nitric oxide and peroxynitrite.
AB - Nitric oxide (.NO) and peroxynitrite (ONOO-) inhibit enzymes that depend on metal
cofactors or oxidizable amino acids for activity. Since xanthine oxidase (XO) is
a 2(2Fe2S) enzyme having essential sulfhydryl groups linked with Mo-pterin
cofactor function, the influence of .NO and ONOO- on purified bovine XO was
determined. Physiological (=1 microM) and supraphysiological (=100 microM)
concentrations of dissolved .NO gas did not inhibit the catalytic activity or
alter the spectral characteristics of XO at 25 degreesC and pH 7.0, differing
from reports showing XO inhibition by .NO. The apparent decrease in XO activity
observed previously was the result of depressed rates of uric acid accumulation
in XO assay systems, due to ONOO--mediated oxidation of uric acid upon reaction
of residual .NO with XO-derived superoxide (O*-2). Nitric oxide derived from S
nitrosoglutathione also did not inhibit cultured vascular endothelial cell XO
activity. In contrast, purified and vascular endothelial cell catalase, a heme
enzyme reversibly inhibited by .NO, was inhibited by similar concentrations and
rates of production of . NO. In contrast to .NO, ONOO- inhibited XO (0.2 microM,
50 mU/ml) with an IC50 of 57 microM (for 3 microM/min infusion of ONOO-) or 120
microM (for bolus addition of ONOO-). Addition of 1% bovine serum albumin, 50
microM xanthine, or 10 microM uric acid protected XO from inactivation by ONOO-.
Thus, in the presence of purine substrates and other more readily oxidized
components of the biological milieu, XO should not be inhibited by either .NO or
ONOO-. These observations reveal that .NO will not serve as an indirect
antioxidant by inhibiting XO-derived production of reactive species and that the
XO-derived products O*-2 and uric acid readily modify the reactivities of .NO and
ONOO-.
PMID- 9647661
TI - Spontaneous conversion of L-dehydroascorbic acid to L-ascorbic acid and L
erythroascorbic acid.
AB - Dehydroascorbic acid, an oxidation product of ascorbic acid (vitamin C),
spontaneously decomposed at neutral and higher pH levels to form three products
that could be quantitated by HPLC-electrochemical analysis. One of the products
was ascorbic acid, suggesting that dehydroascorbic acid was reduced to ascorbic
acid without adding an exogenous reductant. The major newly produced compound was
almost identical to ascorbic acid by UV spectroscopy, which therefore potentially
interfered in the study of ascorbic acid metabolism. The ascorbic acid-like
compound was isolated by reversed-phase HPLC and identified as L-erythroascorbic
acid by mass spectrometry. Fe(II) and Cu(I) increased, whereas desferrioxamine, a
potent iron chelator, inhibited L-erythroascorbic acid production. Phosphate,
used as buffer, and cyanide greatly enhanced dehydroascorbic acid conversion to L
erythroascorbic acid. The identification of L-erythroascorbic acid and its
quantitation by an electrochemical method provides a useful tool for future study
of dehydroascorbic acid metabolism.
PMID- 9647662
TI - A serine proteinase inactivator inhibits chondrocyte-mediated cartilage
proteoglycan breakdown occurring in response to proinflammatory cytokines.
AB - The role played by serine proteinases with trypsin-like specificity in
chondrocyte-mediated cartilage proteoglycan breakdown was investigated by use of
a selective proteinase inactivator, 7-amino-4-chloro-3-(-3
isothiureidopropoxy)isocoumarin, in explant culture systems. This compound was a
rapid inactivator of urokinase-type plasminogen activator. It potently inhibited
interleukin 1- and tumor necrosis factor-stimulated proteoglycan release from
both nasal and articular cartilage. Its less potent inhibition of basal and
retinoic acid-stimulated release appeared to be due to cytotoxic effects. The
functional half-life of the inactivator in culture medium was 95 min, and its
concentration in cartilage was 2.5-fold higher than in the surrounding medium.
Following spontaneous hydrolysis the breakdown products of the inactivator were
unable to inhibit proteoglycan release. Trypsin-like activity was demonstrated by
enzyme histochemistry to be chondrocyte-associated and inhibited by the serine
proteinase inactivator. Cell-associated and secreted plasminogen activator
activity was detected by zymography. These results suggest the involvement of a
serine proteinase(s) with trypsin-like specificity, possibly urokinase-type
plasminogen activator, in chondrocyte-mediated cartilage proteoglycan breakdown
occurring as a result of stimulation with proinflammatory cytokines. Basal
proteoglycan breakdown may occur via a different pathway. Our findings point to a
pathological role for serine proteinase(s) in the development of cartilage
diseases such as arthritis, possibly in a cascade which results in the activation
of the enzyme(s) directly responsible for proteoglycan breakdown. It remains to
be shown whether the target serine proteinase is urokinase-type plasminogen
activator.
PMID- 9647663
TI - Purification to homogeneity and properties of plant glucosidase I.
AB - Glucosidase I was purified about 3600-fold to apparent homogeneity from the
microsomal fraction of mung bean seedlings. The purified enzyme removed the
terminal alpha1,2-linked glucose from Glc3Man9GlcNAc2-peptide or the
endoglucosaminidase H (Endo H)-released oligosaccharide. Glucosidase I activity
was inhibited by kojibiose [Glc(alpha1-2)Glc], but not by other glucose
disaccharides. Removal of up to four mannose residues from the N-linked
oligosaccharide had little effect on its utilization as a substrate for
glucosidase I. The enzyme had a subunit molecular weight of 97 kDa on SDS gels
and this was shifted to 94 kDa after treatment with Endo H or Endo F, suggesting
that glucosidase I is an N-glycoprotein having one oligomannose-type
oligosaccharide. Amino acid sequences of this enzyme showed considerable identity
to the enzyme cloned from a human hippocampus cDNA library. The enzyme was
inhibited by castanospermine, deoxynojirimycin, MDL, and trehazolin, but not by
australine or kifunensine. On the other hand, the other processing glucosidase,
glucosidase II, is sensitive to inhibition by australine, but not by trehazolin.
Thus, these two inhibitors are useful to distinguish glucosidase I from
glucosidase II. The mung bean glucosidase I is quite sensitive to the histidine
modifying reagent diethyl pyrocarbonate, whereas the pig liver glucosidase I is
not. On the other hand, pig liver and pig brain glucosidase I preparations are
sensitive to the sulfhydryl reagent NEM (N-ethylmaleimide), whereas the plant
enzyme is not. These sensitivities to amino acid modifiers suggest significant
differences between the plant and animal glucosidase I, in terms of catalytic
site or protein conformation.
PMID- 9647664
TI - Calcium-induced quenching of intrinsic fluorescence in brain myosin V is linked
to dissociation of calmodulin light chains.
AB - Myosin V isolated from chick brain (BM V) is a multimeric protein of about 640
kDa consisting of two intertwined heavy chains of 212 kDa and multiple light
chains of 10 to 20 kDa. A distinctive feature of the heavy chain is an extended
neck region with six consensus IQ sites for the binding of calmodulin (CaM) and
myosin light chains. The actin-activated MgATPase has been shown to require >/=1
microM Ca2+ for full activity, and evidence points to a myosin-linked regulatory
system where the CaM light chains participate as modulators for the Ca2+ signal.
Still, the precise mechanism of Ca2+ regulation remains unknown. In the present
study we have used the intrinsic tryptophan fluorescence of native BM V to
monitor conformational changes of BM V induced by Ca2+, and we relate these
changes to CaM dissociation from the BM V molecule. The fluorescence intensity
decreases approximately 17% upon addition of sub-micromolar concentrations of
Ca2+ (K0.5 = 0.038 microM). This decrease in fluorescence, which is dominated by
a conformational change in the heavy chain, can be reversed by addition of 1, 2
di(2-aminoethoxy)ethane-N,N,N',N'tetraacetic acid (EGTA) followed by an excess of
CaM, but not by addition of EGTA alone. Gel filtration of native BM V using HPLC
shows that CaM is partially dissociated from the heavy chain in EGTA and
dissociates further upon addition of sub-micromolar concentrations of Ca2+. These
observations suggest that the affinity of CaM for at least one of the IQ sites on
the BM V heavy chain decreases with Ca2+ and that the Ca2+ concentration required
for this effect is lower than that needed to activate acto-BM V. Using a
cosedimentation assay in the presence of actin, we also observe partial
dissociation of CaM when Ca2+ is absent, but now the addition of Ca2+ has a
biphasic effect: sub-micromolar Ca2+ concentrations lead to reassociation of CaM
with the heavy chain, followed by dissociation when Ca2+ exceeds 5-10 microM.
Thus, the binding of CaM to BM V is affected by both actin and Ca2+.
PMID- 9647665
TI - Antiradical and chelating effects in flavonoid protection against silica-induced
cell injury.
AB - Quercetin, dihydroquercetin, and rutin are capable of scavenging superoxide anion
(rate constants of the reaction with superoxide at pH 10 were 1.7 x 10(5), 1.5 x
10(5), and 0.5 x 10(5) M-1 s-1, respectively). At the same time rutin and
quercetin but not dihydroquercetin are iron ion chelators. These substances were
used to elucidate the role of radical scavenging and iron chelating in flavonoid
protection against asbestos-induced oxidative cellular injury. Exposure of rat
peritoneal macrophages to chrysotile asbestos fibers resulted in "frustrated"
phagocytosis, cell injury, and a LDH release. Quercetin, dihydroquercetin, and
rutin were effective in protecting the phagocytic cells against injury caused by
asbestos. Moreover, these flavonoids exhibited cellular protection in the same
order of effectiveness as that observed for the quenching of superoxide:
quercetin > dihydroquercetin > rutin. Exposure of human red blood cells to
asbestos fibers also caused progressive cell injury and lysis. Quercetin and
rutin protected the red cells (quercetin > rutin), whereas dihydroquercetin was
ineffective in preventing asbestos-induced hemolysis. The protective ability of
quercetin and rutin may be related to their iron-chelating activity. Due to this
these flavonoids can be located on asbestos surface in sites of initiation of
free radical reactions and their antiradical moieties can scavenge reactive
oxygen species immediately after the appearance. Thus, both antiradical and
chelating effects appear to be involved in the flavonoid protection against
silica-induced cell injury.
PMID- 9647666
TI - Purification and characterization of a thermostable class II fumarase from
Thermus thermophilus.
AB - A thermostable fumarase was purified from a strain of Thermus thermophilus
isolated from a Japanese hot spring. The maximum specific activity of the
purified enzyme was 1740 units/mg at pH 8.0 and 85 degreesC. The enzyme was
composed of four identical subunits with a molecular weight of 46,000 and
displayed other enzymatic characteristics which are common to the class II
fumarases. The thermal stability of the purified enzyme was remarkable, with over
80% of the activity remaining after a 24-h incubation at 90 degreesC. The enzyme
was also resistant to chemical denaturants; 50% of the initial specific activity
was detected in assay mixtures containing 0.8 M guanidine hydrochloride. The
purified enzyme shared an extremely high sequence homology with Thermus aquaticus
fumarase and Bacillus subtilis fumarase in the first 43 amino acid residues.
PMID- 9647667
TI - Studies on the interaction between ferritin and ceruloplasmin.
AB - We showed previously that ceruloplasmin associates with the H chain of rat liver
ferritin during iron loading into ferritin such that the iron oxidized by
ceruloplasmin was deposited into ferritin [S.-H. Juan et al. (1997) Arch.
Biochem. Biophys. 341, 280-286]. Three synthetic decapeptides derived from
domains 2, 4, and 6 of ceruloplasmin, referred to CP-2, CP-4, and CP-6, were
utilized to identify a possible binding site on ceruloplasmin for ferritin. Two
of the peptides, CP-4 and CP-6, were found to inhibit iron loading into the
recombinant ferritin H chain homopolymer (rH-Ft) by ceruloplasmin. The extent of
inhibition of iron loading into ferritin by ceruloplasmin by CP-6, but not CP-4,
varied with pH, whereas the inhibitory effect remained constant in increasing
concentrations of NaCl. The addition of rH-Ft quenched the fluorescence emission
of CP-4 and CP-6, but not CP-2. The quenching of fluorescence was used to
estimate dissociation constants for the peptides. Iron loading into ferritin in
Hepes buffer was not affected in the presence of these peptides. In addition,
synthetic peptides corresponding to the BC loop of ferritin H and L chains were
utilized to localize an interaction site on ferritin for ceruloplasmin. The BC
loop of H chain but not L chain of ferritin stimulated the ferroxidase activity
of ceruloplasmin. Only the BC loop of ferritin H chain decreased the amount of
iron loading into ferritin by ceruloplasmin.
PMID- 9647668
TI - Properties of the novel intermediate filament protein synemin and its
identification in mammalian muscle.
AB - We examined specific properties of highly purified synemin (230 kDa), recently
identified as a novel intermediate filament (IF) protein, from avian smooth
muscle. Soluble synemin in 10 mM Tris-HCl, pH 8.5, appears as approximately 11-nm
diameter globular structures by negative-stain and low-angle shadow electron
microscopy. Chemical crosslinking and SDS-PAGE analysis indicate that soluble
synemin molecules contain two 230-kDa subunits. The pH- and ionic strength
dependent solubility properties of synemin are similar to those of the type III
IF protein desmin, but under physiological-like conditions in which desmin self
assembles into long approximately 10-nm-diameter IFs, synemin self-associates
into complex, approx 15- to 25-nm-diameter globular structures. Calpain digestion
demonstrated that synemin is extremely proteolytically labile. Western blot
analysis, with monospecific polyclonal antibodies against avian synemin, shows
the presence of the reactive 230-kDa synemin band in samples of adult avian
skeletal, cardiac, and smooth muscle and of two reactive bands at approximately
225 kDa (major) and approximately 195 kDa in adult porcine skeletal, cardiac, and
smooth muscle. Partial purification of synemin from porcine smooth muscle also
resulted in fractions highly enriched in the approximately 225- and approximately
195-kDa polypeptides. Conventional immunofluorescence and immunoconfocal
microscopy of isolated myofibrils and of frozen sections also demonstrated, for
the first time, that synemin is present in all three adult porcine muscle cell
types and is colocalized with desmin in skeletal and cardiac muscle cells at the
myofibrillar Z-lines.
PMID- 9647669
TI - Inhibition of 25-hydroxyvitamin D3 production by 1, 25-dihydroxyvitamin D3 in
rats.
AB - The regulation of the hepatic vitamin D3 25-hydroxylase enzyme system by 1,25
dihydroxyvitamin D3 was examined using male rats. Circulating 25-hydroxyvitamin
D3 levels decreased in response to increasing doses of 1,25-dihydroxyvitamin D3
as determined by HPLC and serum protein binding assay. A maximum reduction in
serum 25-hydroxyvitamin D3 of 57.7% was achieved by the administration of 1,25
dihydroxyvitamin D3 and higher doses produced no further reduction. The in vitro
rate of vitamin D 25-hydroxylation by liver homogenates from rats given 1,25
dihydroxyvitamin D3 was also reduced by 60.4%. Whole rat extracts from animals
given [3H]vitamin D3 contained 50.4% less 25-[3H]hydroxyvitamin D3 in treated
rats given 1,25-dihydroxyvitamin D3 than in those given only the vehicle.
Further, 1,25-dihydroxyvitamin D3 treatment had no effect on in vivo
disappearance of 25-[3H]hydroxyvitamin D3. Taken together, these results
demonstrate that the decrease in 25-hydroxyvitamin D3 levels observed in 1,25
dihydroxyvitamin D3-treated rats results from a decrease in production and not an
increase in the metabolic clearance of 25-[3H]hydroxyvitamin D3.
PMID- 9647670
TI - Massive production of farnesol-derived dicarboxylic acids in mice treated with
the squalene synthase inhibitor zaragozic acid A.
AB - The zaragozic acids are potent inhibitors of squalene synthase. In vivo studies
in mice confirmed our earlier observations that inhibition of squalene synthase
by zaragozic acid A was accompanied by an increase in the incorporation of label
from [3H]mevalonate into farnesyl-diphosphate (FPP)-derived isoprenoic acids (J.
D. Bergstrom et al., 1993, Proc. Natl. Acad. Sci. USA 90, 80-84). Farnesyl
diphosphate-derived metabolites appear transiently in the liver. We were unable
to detect any farnesol formation in the zaragozic acid-treated animals which
indicates that FPP is readily converted to farnesoic acid and dicarboxylic acids
in the liver. These metabolites were found to be produced only in the liver and
not in the kidney. trans-3,7-Dimethyl-2-octaen-1,8-dioic acid and 3, 7
dimethyloctan-1,8-dioic acid were identified as the major end products of
farnesyl-diphosphate metabolism in the urine of mice treated with zaragozic acid
A. Quantitative analysis of these FPP-derived dicarboxylic acids by gas-liquid
chromatography revealed that approximately 11 mg of total dicarboxylic acids is
excreted per day into the urine of a mouse after 3 days of treatment with
zaragozic acid A.
PMID- 9647671
TI - Inhibition by butylmalonate of proton influx in nonphosphorylating mitochondria.
AB - The impermeability of the inner membrane to protons is one of the four postulates
of the chemiosmotic theory on the coupling mechanism between respiration and
phosphorylation in mitochondria. However, oxygen uptake in isolated
nonphosphorylating mitochondria requires that protons translocated from inside to
outside must be, at least in part, retaken up. The nonohmic relationship between
the respiration rate and the protonmotive force has been mainly ascribed to an
increase in the proton conductance of the inner membrane (proton leak). In liver
mitochondria oxygen pulse experiments the rate of both the efflux and the reentry
of protons, linked to the oxygen consumption supported by succinate oxidation, is
greatly stimulated by low concentrations of butylmalonate. The steady-state level
of protons exported outside in the acidification-alkalinization cycle of the
medium, generated by an oxygen pulse, is also increased but the rate of oxygen
uptake is unaffected. However, in valinomycin-stimulated respiration
butylmalonate inhibits the ratio of proton influx/oxygen consumption by 50% and
also stimulates the ratio of proton efflux/oxygen consumption by 50%. Titration
of the butylmalonate effect gives a saturation curve with a half-maximal effect
at 5 microM. Identical results are obtained inthe presence of oligomycin which
excludes the involvement of the ATP-synthase complex. The data obtained are not
in contrast with the existence in the inner membrane of a channel-like system
inhibited by butylmalonate and involved, together with other systems, in
promoting the backflow of protons in nonphosphorylating state 4 respiration. Such
a system, similar to thermogenin, could be involved in tissues, other than
adipose, in a more general thermogenesis program by promoting the dissipation as
heat of the energy given by the electrochemical proton gradient. The possibility
that butylmalonate might inhibit the proton movement associated with cation and
anion transport in mitochondria has also been considered.
PMID- 9647672
TI - Contribution of basic residues of the D and H helices in heparin binding to
protein C inhibitor.
AB - Protein C inhibitor (PCI) is a heparin-binding serine protease inhibitor (serpin)
that regulates hemostatic proteases such as activated protein C (APC) and
thrombin. The work described here provides further evidence that the PCI H helix,
but not the D helix, has a major role in heparin-accelerated inhibition of APC
and thrombin. We previously identified Arg-269 and Lys-270 of the H helix
[R269A/K270A "H1" recombinant PCI (rPCI)] as important residues both for heparin
accelerated inhibition of thrombin and APC and for heparin-Sepharose binding
(Shirk, R. A., Elisen, M. G. L. M., Meijers, J. C. M., and Church, F. C. (1994)
J. Biol. Chem. 269, 28690-28695). H1 rPCI was used as a template for Ala-scanning
mutagenesis of other H helix basic residues (H1-K266A, H1-K273A, and H1
K266A/K273A) and of the D helix basic residues (H1-K82A, H1-K86A, H1-R90A, and H1
K82A/K86A/R90A). Compared to wild-type rPCI/heparin (k2 = 2.2 x 10(7) M-1 min-1
for thrombin), heparin-accelerated thrombin inhibition was decreased 2.4-fold by
H1 rPCI, 4.4-fold by H1-K266A rPCI, and 8-fold by H1-K273A rPCI. H1-K266A/K273A
rPCI thrombin inhibition was essentially not accelerated by heparin. A similar
trend was found for APC-heparin inhibition using these H helix rPCI mutants. In
contrast, the D helix rPCI mutants did not have further reduced heparin
stimulated thrombin or APC inhibition compared to H1 rPCI. Interestingly, all of
the H and D helix rPCI mutants had reduced heparin-Sepharose binding activity
(ranging from 180 to 360 mM NaCl) compared to wild-type rPCI and H1 rPCI, which
eluted at 650 and 430 mM NaCl, respectively. These data suggest that all four
basic residues (Lys-266, Arg-269, Lys-270, Lys-273) in the H helix of PCI form a
heparin binding site. Our results also imply that while the D helix basic
residues (Lys-80, Lys-86, and Arg-90) contribute to overall heparin binding, they
are not necessary for heparin-accelerated activity. We conclude that the primary
heparin binding site of PCI is the H helix and not the D helix as found in other
homologous heparin-binding serpins such as antithrombin III, heparin cofactor II,
and protease nexin 1.
PMID- 9647673
TI - Mechanism-based inhibition of human folylpolyglutamate synthetase: design,
synthesis, and biochemical characterization of a phosphapeptide mimic of the
tetrahedral intermediate.
AB - Folylpolyglutamate synthetase (FPGS) catalyzes anATP-dependent ligation reaction
that results in the synthesis of poly(gamma-glutamate) metabolites of folates and
some antifolates. We have synthesized and characterized the prototype of a new
class of mechanism-based FPGS inhibitor in which a phosphonate moiety mimics the
tetrahedral intermediate formed during the ligation reaction. This phosphonate, 4
amino-4-deoxy-10-methyl-pteroyl-L-glutamyl-gamma-[Psi?P(O)(OH)-O?] glutarate (4
NH2-10-CH3-Pte-L-Glu-gamma-[Psi?P(O)(OH)-O?]glutarate), is not a substrate for
human FPGS, but is a linear, competitive inhibitor (Kis = 46 nM) with respect to
methotrexate as the variable substrate. Inhibition is not time-dependent and
preincubation of FPGS with this phosphonate does not increase the degree of
inhibition, suggesting that it is not a slow, tight-binding inhibitor involving a
time-dependent isomerization, EI --> EI*. Substructures containing the
phosphonate moiety but lacking the pterin are much less inhibitory to FPGS,
indicating that a significant portion of the inhibitor binding energy is derived
from the pterin moiety, a feature also observed in substrate binding. 4-NH2-10
CH3-Pte-L-Glu-gamma-[Psi?P(O)(OH)-O?]glutarate is also an analog of a proposed
tetrahedral intermediate in the reaction catalyzed by gamma-glutamyl hydrolase
(gamma-GH), another enzyme of importance in controlling folate homeostasis in
cells. This intermediate would arise from direct attack of H2O on the dipeptide,
4-NH2-10-CH3-Pte-L-Glu-gamma-L-Glu. The fact that 4-NH2-10-CH3-Pte-L-Glu-gamma
[Psi?P(O)(OH)-O?]glutarate is not an inhibitor of gamma-GH strongly suggests that
hydrolysis of poly-gamma-glutamates catalyzed by gamma-GH does not involve the
direct attack of water at the scissile amide bond. Methotrexate, its gamma
glutamyl dipeptide metabolite, and 4-NH2-10-CH3-Pte-L-Glu-gamma-[Psi?P(O)(OH)
O?]glutarate are equipotent as inhibitors of human dihydrofolate reductase (the
primary target of methotrexate), but the phosphonate does not significantly
inhibit another important folate-dependent enzyme, thymidylate synthase. Thus,
the phosphonate moiety in this analog represents an important new lead in the
development of FPGS inhibitors.
PMID- 9647674
TI - Carbohydrate gluing is a strategy for supramolecular clamping of submultiples in
annelid extracellular multi-subunit hemoglobin.
AB - A key to understanding the mysterious hierarchic organization of annelid multi
subunit extracellular hemoglobin (giant Hb, composed of 144 globin chains and
about 36 nonheme chains called linkers) is knowing the role of linkers in holding
together the entire two-tiered hexagonal form. Here, the effects of added
monosaccharides on the dissociation of giant Hb from the marineworm Perinereis
aibuhitensis were monitored using dynamic light scattering (DLS), transmission
electron microscopy (TEM), and circular dichroism (CD) measurements. Changes in
Stokes radius and more clearly the distribution analysis of the Hb based on the
DLS measurements showed that Hb preferentially dissociates into hexagonal units
(called submultiples), which was consistent with the results of TEM and CD
measurements. The results thus show that linkers specifically "clamp"
submultiples together to organize the two-tiered form through carbohydrate
gluing. Thus, a submultiple behaves like an ordinary protein, whereas the intact
Hb behaves like a miniature supramolecular system. This clamp model is plausible
because it inherently involves catastrophe of the molecular stoichiometry at the
two-tiered hexagonal formation level because carbohydrates are under
posttranslational regulation and therefore contain structural ambiguity.
PMID- 9647677
TI - What is line bisection in unilateral spatial neglect? Analysis of perceptual and
motor aspects in line bisection tasks.
AB - Three patients with unilateral spatial neglect could detect the difference of
length between the right and left segments when a line had a transection mark. To
examine the effect of response mode, the manual line bisection task and a new
"line bisection task by fixation" were given to the patients. In tasks that used
lines with no landmark, they showed apparent rightward errors. The results
suggest that line bisection is not a task that examines the ability of patients
with neglect to compare the right and left extents of a line. Where to fixate as
the subjective midpoint may determine the rightward errors of bisection, whether
manual response is used or not.
PMID- 9647675
TI - Cyclic peptides as probes of the substrate binding site of the cytosolic tyrosine
kinase, pp60c-src.
AB - A series of 48 cyclic peptides based on the amino acid sequence surrounding the
autophosphorylation site of pp60(c-src) was synthesized and each was tested as
both a substrate and an inhibitor of this protein tyrosine kinase. Starting with
cyclo(Asp1-Asn2-Gln3-Tyr4-Ala5-Ala6-Arg7-Gln8-d- Phe9-Pro10) a six-amino-acid
survey was performed at positions 1 through 8 to determine which positions were
critical for affinity and phosphorylation and which amino acids produced the
greatest activity. Our survey found that Arg7 was detrimental for binding and
phosphorylation and that aromatic residues were preferred at this position.
Further increases in affinity were obtained with hydrophobic residues at position
6 with the optimum for both affinity and phosphorylation being Phe. Changes on
the "amino-terminal" side of Tyr4 resulted in reduced Vmax values, illustrating
the requirement for acidic residues in peptidic tyrosine kinase substrates. The
result of the survey was cyclo(Asp1-Asn2-Gln3-Tyr4-Ala5-Phe6-Phe7-Gln8-d-Phe 9
Pro10). The change of residues 6 and 7 resulted in a 42-fold increase in affinity
and no increase in Vmax. As a substrate, this peptide displayed Michaelis-Menten
kinetics at saturating ATP conditions. As an inhibitor, mixed inhibition was
observed. A linear version of this peptide was 13-fold less potent an inhibitor
than the cyclic peptide.
PMID- 9647678
TI - Relationships among multiple task asymmetries. I. A critical review.
AB - Previous multiple-task experiments examining relationships among lateral
difference measures have been interpreted as supporting (a) both global and local
relationships or (b) local relationships only. The evidence from principle
components, correlational, and factor analytic approaches is reviewed with the
aim of reconciling the literature. Although a principle component has been
reported to which all asymmetries correlate positively, it may not reflect
existing null and negative correlations between pairs of measures. All three
literatures make clear that such correlations exist, calling into question the
reality of a global relationship. In contrast, all three approaches find evidence
supporting the reality of local relationships. Factor analytic approaches most
fully develop local relationships and permit interpretation in terms of
hemispheric processes, but they need to (a) use larger sample sizes, (b)
prescreen measures for reliability, and (c) make publicly available the
underlying correlational matrices.
PMID- 9647679
TI - Relationships among multiple task asymmetries. II. A large-sample factor
analysis.
AB - Samples from published and unpublished factor analytic studies of multiple task
asymmetry are combined to produce a large-sample factor analysis of 10 measures,
prescreened for significant asymmetry and acceptable reliability, from 9
lateralized tasks. A full correlational matrix is presented, with task pairings
having sample sizes ranging from 103 to 479 (mean N = 290). Both significant
positive and significant negative correlations between measures are found.
Extraction and oblique rotation of five factors fails to reveal any evidence of a
global relationship among lateral difference measures, and principal-components
analysis likewise fails to reveal a component to which all measures correlate
positively. However, evidence for local structure is found. Results are
interpreted in terms of dissociable hemispheric processes, and consideration is
given of the possible existence of modality-specific characteristic perceptual
asymmetry and of single versus multiple determination of lateral differences.
PMID- 9647680
TI - The representation of arithmetic facts in memory: results from retraining a brain
damaged patient.
AB - This single case study was designed to gather evidence regarding whether the
mental representations mediating multiplication fact retrieval make use of single
or multiple codes. MC is a brain-damaged volunteer whose numerical processing
impairments were limited to multiplication fact retrieval. He relearned three
sets of multiplication facts. Each set was relearned in one of three input
formats: Arabic, written verbal, or spoken verbal. Following training all facts
were tested in all input formats. MC's posttraining performance was virtually
error free and showed no effects of input format. However, reaction-time data
showed fact retrieval was fastest when the training format matched the test
format. Results are discussed in relation to single- and multiple-code models of
multiplication fact retrieval.
PMID- 9647681
TI - A twin and family study of the association between immune system dysfunction and
dyslexia using blood serum immunoassay and survey data.
AB - We conducted a study of the association between developmental reading disability
(DRD) and immune disorders (ID) using both survey and immunoassay data in two
separate samples of families. One sample was made up of twins and their parents
and was ascertained through a population-based sampling scheme. The other sample
was a set of extended pedigrees selected for apparent autosomal dominant
transmission of DRD. We failed to find an association between DRD and ID in
either sample, regardless of the method used to assess immune system function.
Even though our twin sample provided evidence that both DRD and immune conditions
were significantly heritable, there was no evidence for a genetic correlation
between ID and DRD nor was there any clear indication that a special subgroup of
individuals may be comorbid for these conditions because of genetic reasons. How
these negative findings can be reconciled with the developmental hypothesis of
Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene
locus influencing DRD that has been recently located in the HLA region of the
short arm of chromosome 6 is discussed.
PMID- 9647682
TI - Sex differences in object location memory.
AB - The ability to remember where objects were is thought to require multiple
separate processes. One has to encode the precise positions occupied, assign the
various objects to the correct (relative) locations, and achieve an integration
of both types of spatial information. This study examined whether sex differences
exist for these selective components of object location memory. Twenty males and
20 females participated in the following task. On a PC screen, they were shown a
square with 10 different objects for 30 s. Subsequently, the objects disappeared
from the screen, reappeared in a row above the square, and subjects were asked to
relocate them in three different conditions. In the object-to-position-assignment
condition, the original positions were premarked in the square, so subjects
needed only to assign the correct object to the correct position. In the
positions-only condition, all objects assumed the same identity. Therefore,
subjects had only to reproduce the precise positions. Finally, in the combined
condition, subjects were required to replace all the different objects in the
square without any of object positions premarked. The absolute displacements
between an object's original and its relocated position reflect the integration
mechanism. Females did as well as males in the object-to-position-assignment
condition and on the absolute displacements in the combined condition, but they
were less efficient than males in positional reconstruction per se. Thus, it
seems that the male advantage in spatial memory is not a general effect but
applies only to certain specific processing components. Moreover, the employment
of a dual task during encoding, concurrent articulatory suppression, yielded no
significant interactions with sex. This suggests that females' weaker positional
encoding does not derive from the use of an inefficient verbal strategy.
PMID- 9647683
TI - Stimulus characteristics determine processing approach on random array letter
cancellation tasks.
AB - Target-to-distractor ratio strongly influences performance on typical random
array letter cancellation tasks, suggesting that a "controlled" processing
approach is used. This study was designed to determine whether "automatic"
processing could be also demonstrated in the random array cancellation paradigm
by changing the perceptual characteristics of the stimuli. Thirty-two healthy
subjects sequentially performed four random array cancellation tasks with 50 and
100 stimuli. The letters "I" or "O" were targets and "L" served as the
distractor. Performance was measured by the number of correctly canceled targets
divided by the time to completion, corrected for accuracy. There was a strong
effect of the number of stimuli on forms using I targets (p < .00001), but not
for O's (p = . 15) Performance scores were lower for I target forms than for O
targets. These findings demonstrate that performance approximating "automatic"
processing can also be elicited on clinically useful, office-based, or bedside
tests such as random array cancellation.
PMID- 9647684
TI - The relation of ERP components to complex memory processing.
AB - The relation between various ERP components generated during encoding of a word
and its subsequent recall were investigated using a "rote" serial-order and an
"elaborative" category memory task. Words (flashed separately) were time-locked
to EEG recordings from 21 cortical sites. ERP components from the five subjects
having the highest recall scores were compared to the five lowest scoring
subjects. Results based on the P200 peak amplitude data as well as the N400 and
late positive component peak amplitude and latency data suggest that anterior and
posterior distributional differences are elicited during encoding of words for
rote and elaborative memory tasks. Furthermore, strong individual differences in
these patterns were found as a function of task. A tentative argument was made
that the obtained anterior and posterior differences may index different word
feature selection and encoding processes, which are differentially utilized by
high and low recallers.
PMID- 9647686
TI - Source monitoring: ERP evidence for greater reactivity to nontarget information
in older adults.
AB - Event-Related Potentials (ERPs) were collected concurrently with stimulus
presentation during a source monitoring task. Younger adults were less likely
than older adults to make source monitoring errors and their ERP records showed
far greater discrimination between target stimuli and familiar but nontarget
foils. Older adults not only made more source errors but produced high amplitude
late positivities to the nontarget foils even when these foils were correctly
rejected. Under divided attention conditions, younger adults performance was
similar to that of the older adults both behaviorally and electrophysiologically.
These data illustrate the role that attentional resources play in the ability to
inhibit response tendencies and suggest that age differences in source monitoring
may be more related to attentional control than inefficiencies in the encoding of
contextual information. As well, they suggest that the ERP late positivity may
represent a more general response to item salience rather than serve as an index
of recollection as is the current view.
PMID- 9647685
TI - Sex differences in right hemisphere tasks.
AB - We tested the hypothesis that sex differences in spatial ability and emotional
perception are due to sex differences in intrahemispheric organization of the
right hemisphere. If the right hemisphere is differently organized by sex
primarily specialized for spatial ability in men, but primarily specialized for
emotional perception in women-then there should be a negative correlation between
spatial ability and emotional perception within sex, and the greatest disparity
between abilities should be found in people with characteristic arousal of the
right hemisphere. Undergraduate men (N = 86) and women (N = 132) completed tests
of Mental Rotation, Surface Development, Profile of Nonverbal Sensitivity,
Progressive Matrices, and Chimeric Faces. Although the expected pattern of sex
differences was observed, there was no evidence for the hypothesized negative
correlation between spatial ability and emotional perception, even after
statistical control of general intelligence.
PMID- 9647687
TI - Volume 35, no. 3 (1997) in the poster paper (Article no. BR970966), "26
AB - Copyright
PMID- 9647689
TI - Incorporation and glial differentiation of mouse EGF-responsive neural progenitor
cells after transplantation into the embryonic rat brain.
AB - In vitro, epidermal growth factor (EGF)-responsive neural progenitor cells
exhibit multipotent properties and can differentiate into both neurons and glia.
Using an in utero xenotransplantation approach we examined the developmental
potential of EGF-responsive cells derived from E14 mouse ganglionic eminences,
cortical primordium, and ventral mesencephalon, after injection into the E15 rat
forebrain ventricle. Cell cultures were established from control mice or from
mice carrying the lacZ transgene under control of the promoters for nestin, glial
fibrillary acidic protein (GFAP), or myelin basic protein (MBP). The grafted
cells, visualized with mouse-specific markers or staining for the reporter gene
product, displayed widespread incorporation into distinct forebrain and midbrain
structures and differentiated predominantly into glial cells. The patterns of
incorporation of cells from all three regions were very similar without
preference for the homotopic brain areas. These results suggest that EGF
responsive progenitor cells can respond to host derived environmental cues,
differentiate into cells with glial-like features, and become integrated in the
developing recipient brain.
PMID- 9647690
TI - GFRalpha-4, a new GDNF family receptor.
AB - GFRalpha-1, GFRalpha-2, and GFRalpha-3 constitute a family of structurally
related, glycosyl-phosphatidylinosital-linked, cell surface proteins, two of
which, GFRalpha-1 and GFRalpha-2, are components of the receptor complex for the
neurotrophic factors GDNF and neurturin, respectively. By screening an embryonic
chicken brain cDNA library with a GFRalpha-1 probe at low stringency, we isolated
cDNAs encoding an additional member of the GFRalpha family, GFRalpha-4. The
nucleotide sequence predicts a 431-amino-acid secreted protein that is more
closely related to GFRalpha-1 and GFRalpha-2 than to GFRalpha-3. GFRalpha-4 mRNA
is expressed in distinctive patterns in the brain and several other organs and
tissues of the chicken embryo. Our findings extend the family of GFRalpha
proteins and provide information about the tissues in which GFRalpha-4 may
function during development.
PMID- 9647691
TI - Search for a nuclear localization signal in the prion protein.
AB - Spongiform transmissible encephalopathies are neurodegenerative diseases
characterized by the accumulation, in infected brains, of a pathological form of
a normal host-encoded protein called PrP. Previous data have shown that PrP could
interact with cytosolic factors, including nuclear molecules, emphasizing the
possible function of such interactions. Moreover, in infected cells, PrP is
observed not only at the plasma membrane but also in the nuclear compartment. The
N-terminal extremity of the mature PrP has been thought to harbor a nuclear
localization signal reminiscent of the nuclear localization signal of the simian
virus 40 large T antigen. By designing a fusion protein between the putative
nuclear localization signal of PrP and the green fluorescent protein, we have
shown that the N-terminal sequence of PrP is not efficient in targeting the
protein in the nuclear compartment. This implies new insights regarding the way
by which PrP could, however, reach the nuclear compartment.
PMID- 9647692
TI - Parallel molecular genetic pathways operate during CNS metamorphosis in
Drosophila.
AB - Insect metamorphosis provides a valuable model for studying mechanisms of steroid
hormone action on the nervous system during a dynamic phase of functional
remodeling. The Drosophila Broad Complex (BRC) holds a pivotal position in the
gene expression cascade triggered by the molting hormone 20-hydroxyecdysone (20E)
at the onset of metamorphosis. We previously demonstrated that the BRC, which
encodes a family of zinc-finger transcription factors, is essential for
transducing 20E signals into the morphogenetic movements and cellular assembly
that alter the CNS from juvenile to adult form and function. We set out to
examine the relationship of BRC to two other genes, IMP-E1 and Deformed (Dfd),
involved in the metamorphic transition of the CNS. Representatives of the whole
family of BRC transcript isoforms accumulate in the CNS during the larval-to
pupal transition and respond directly to 20E in vitro. IMP-E1 is also directly
regulated by 20E, but its induction is independent of BRC, revealing that 20E
works through at least two pathways in the CNS. DFD expression is also
independent of BRC function. Surprisingly, BRC and DFD proteins are expressed in
distinct, nonoverlapping subsets of neuronal nuclei of the subesophageal ganglion
even though both are required for its migration into the head capsule. This
suggests that the segment identity and ecdysone cascades operate in parallel to
control region-specific reorganization during metamorphosis.
PMID- 9647693
TI - Atrophin-1, the DRPLA gene product, interacts with two families of WW domain
containing proteins.
AB - Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for
dentatorubral and pallidoluysian atrophy (DRPLA). The normal function of atrophin
1 is unknown. We have identified five atrophin-1 interacting proteins (AIPs)
which bind to atrophin-1 in the vicinity of the polyglutamine tract using the
yeast two-hybrid system. Four of the interactions were confirmed using in vitro
binding assays. All five interactors contained multiple WW domains. Two are
novel. The AIPs can be divided into two distinct classes. AIP1 and AIP3/WWP3 are
MAGUK-like multidomain proteins containing a number of protein-protein
interaction modules, namely a guanylate kinase-like region, two WW domains, and
multiple PDZ domains. AIP2/WWP2, AIP4, and AIP5/WWP1 are highly homologous, each
having four WW domains and a HECT domain characteristic of ubiquitin ligases.
These interactors are similar to recently isolated huntingtin-interacting
proteins, suggesting possible commonality of function between two proteins
responsible for very similar diseases.
PMID- 9647694
TI - CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0
family members, NMDA receptor subunits, neurexins, and neuroligins.
AB - We report a novel multivalent PDZ domain protein, CIPP (for channel-interacting
PDZ domain protein), which is expressed exclusively in brain and kidney. Within
the brain, the highest CIPP mRNA levels were found in neurons of the cerebellum,
inferior colliculus, vestibular nucleus, facial nucleus, and thalamus.
Furthermore, we identified the inward rectifier K+ (Kir) channel, Kir4.1 (also
called "Kir1.2"), as a cellular CIPP ligand. Among several other Kir channels
tested, only the closely related Kir4.2 (or "Kir1.3") also interacted with CIPP.
In addition, specific PDZ domains within CIPP associated selectively with the C
termini of N-methyl-D-aspartate subtypes of glutamate receptors, as well as
neurexins and neuroligins, cell surface molecules enriched in synaptic membranes.
Thus, CIPP may serve as a scaffold that brings structurally diverse but
functionally connected proteins into close proximity at the synapse. The
functional consequences of CIPP expression on Kir4.1 channels were studied using
whole-cell voltage clamp techniques in Kir4.1 transfected COS-7 cells. On
average, Kir4.1 current densities were doubled by cotransfection with CIPP.
PMID- 9647695
TI - Mycosis of bandedwinged whitefly (Trialeurodes abutilonea) (Homoptera:
aleyrodidae) caused by Orthomyces aleyrodis gen. & sp. nov. (Entomophthorales:
Entomophthoraceae).
AB - A new genus and species of fungus, Orthomyces aleyrodis Steinkraus, Humber &
Oliver gen. & sp. nov. (Entomophthorales: Entomophthoraceae) is described. In
1994 and 1995, this fungus caused epizootics in high populations of bandedwinged
whitefly (Trialeurodes abutilonea) on cotton and cocklebur in Alabama. In 1996,
T. abutilonea populations were lower and no infected specimens were found. This
is the first report of an entomophthoralean infecting an aleyrodid in the New
World and the first report of entomophthoralean epizootics in whiteflies.
PMID- 9647696
TI - Histopathological effects of Bacillus thuringiensis on the alimentary canal of
the sheep louse, Bovicola ovis.
AB - Sequential observations were made of the ultrastructural effects of Bacillus
thuringiensis (Bt) subsp. kurstaki strain WB3S16 on midgut epithelial cells of
the sheep biting louse, Bovicola ovis, after the lice were fed, ad libitum, a
powdered preparation of Bt spores, delta-endotoxin crystals, and lysed cellular
components. Light microscope observations revealed cytopathological changes to
the midgut epithelial cells 4 h postfeeding. Transmission electron micrographs
showed that the microvilli of the midgut epithelial cells became disrupted 4-8 h
postfeeding, after which the cells became vacuolated and swollen, and the cell
organelles lost definition and disappeared. Paralysis and death of B. ovis
occurred between 8 and 12 h postfeeding, coincident with midgut cells lysis and
release of cellular contents into the midgut lumen. The histopathological effects
reported here are similar to those reported in lepidopteran and coleopteran
larvae affected by the delta-endotoxin crystal proteins. The constituent
fractions of the Bt preparation were tested for toxicity to B. ovis using a
feeding bioassay. Native delta-endotoxin crystals were not toxic to B. ovis and
remained intact in the midgut of the insect. There was no evidence that the
native Bt crystal was involved in the cytopathology and death of the lice.
However, in vitro solubilized delta-endotoxin crystal proteins were significantly
toxic to B. ovis. In addition, a louse active toxin was associated with the Bt
membranes and culture supernatant.
PMID- 9647697
TI - Characterization of isolates of Paenibacillus larvae subsp. larvae from diverse
geographical origin by the polymerase chain reaction and BOX primers.
AB - Ninety-nine strains of Paenibacillus larvae subsp. larvae, the causal agent of
American Foulbrood disease (AFB) of honeybees, were isolated from different
regions of Argentina and other countries. The isolates were characterized on the
basis of DNA fingerprints by a polymerase chain reaction technique (PCR) with BOX
sequence-specific primers. Isolates from Argentina generated three groups of
patterns (designated A, B, and C), while P. larvae subsp. larvae strains obtained
from other countries yielded two distinguishable patterns (coincident with A and
B). Strains from U.S. A. and Germany were identical and related to Group A, while
all Czech and English isolates belonged to Group B. Strains from France, Poland,
Italy, Sweden, and New Zealand showed two different patterns (A and B).
Comparisons of the biochemical type and genotype of isolates rendered no obvious
linkage between both features. These results suggest that AFB in Argentina
resulted from multiple sources of contaminated material.
PMID- 9647699
TI - Infectivity and pathogenicity of Baculovirus penaei (BP) in cultured larval and
postlarval Pacific white shrimp, Penaeus vannamei, related to the stage of viral
development.
AB - The infectivity and pathogenicity of the penaeid shrimp virus, Baculovirus penaei
(BP), is influenced by the stage of viral development. This study consisted of a
preliminary experiment which showed that nonocculuded virus administered per os
is infective, followed by two infectivity experiments. In the first phase of each
infectivity experiment, mysis stage larvae of Penaeus vannamei were inoculated
with BP and samples of infected tissue were collected at various times
postinoculation (p.i.). These samples were then used to inoculate either mysis or
postlarval stage P. vannamei in the second phase of each experiment. Viral
inocula prepared from patently infected tissues consistently produced infections
in both mysis and postlarval stage shrimp. Inocula prepared from prepatently
infected tissue collected 12-18 h p.i. produced infections in some, but not all
replicate cultures, while inocula prepared from tissues collected earlier than 12
h p.i. were not infective. Viral development in mysis stage larvae was
substantially delayed and the mortality was significantly lower when the viral
inocula were prepared from prepatently compared to patently infected tissues. BP
appears to be most pathogenic to larvae that have been exposed to inocula
prepared from tissues that had recently developed a high prevalence of patent
infections or about 72 h p.i.
PMID- 9647698
TI - Identification of a novel Lymantria dispar nucleopolyhedrovirus mutant that
exhibits abnormal polyhedron formation and virion occlusion.
AB - In previous studies on the formation of Lymantria dispar nuclear polyhedrosis
virus (LdMNPV) few polyhedra (FP) mutants, several polyhedron formation mutants
(PFM) were identified that appeared to be unique. These viral mutants are being
characterized to investigate the processes of polyhedron formation and virion
occlusion. LdMNPV isolate PFM-1 is one of these mutants, and is described in this
report. Genetic techniques were used to determine if isolate PFM-1 contained a
mutation in the polyhedrin or 25K FP gene. Wild-type viruses were recovered after
coinfection of Ld652Y cells with isolate PFM-1 and a FP mutant, and with isolates
PFM-1 and PFM-C (isolate PFM-C contains a mutation in the polyhedrin gene). These
viruses were analyzed by genomic restriction endonuclease digestion and found to
be chimeras of the original PFMs used in the coinfections. Marker rescue studies
mapped the mutation in isolate PFM-1 to a genomic region that does not include
the polyhedrin or 25K FP genes. Isolate PFM-1 produced approximately 14-fold
fewer polyhedra than LdMNPV isolate A21-MPV, an isolate that produces wild-type
levels of polyhedra, and approximately 2-fold more polyhedra compared to the FP
isolate 122-2. Polyhedra generated by isolate PFM-1 were normal in size and shape
but contained very few viral nucleocapsids. The same amount of budded virus (BV)
was released from cells infected with isolates PFM-1 and A21-MPV. In contrast,
isolate 122-2 yielded significantly more BV than isolates PFM-1 and A21-MPV.
PMID- 9647700
TI - Chemotactic responses of tunicate (Urochordata, Ascidiacea) hemocytes in vitro.
AB - A number of molecules were found to alter the motility of tunicate hemocytes.
Bacterial lipopolysaccharide (LPS) significantly enhanced cell mobility relative
to non-stimulated controls. Responses to LPS were not directional and so
represented chemokinesis. In contrast, checkerboard analyses indicated that two
tunicate hemolymph proteins, tunIL1-alpha and -beta, stimulated truly directional
chemotaxis by hemocytes. The data suggest that tunIL1 proteins may contribute to
defense by altering the localization of immunocompetent cells.
PMID- 9647701
TI - A polydnavirus from the spruce budworm parasitoid, Tranosema rostrale
(Ichneumonidae).
AB - The calyx epithelium of the campoplegine wasp, Tranosema rostrale, contains
typical ichneumonid polydnaviruses (PVs) that display an apparently uncommon
association with the egg chorion. The latter structure features fine hair-like
projections, longest around the egg's apices. In the lumen of the ovary, T.
rostrale virus becomes lodged between these projections and forms a particulate
coat around the egg. In the host, Choristoneura fumiferana, projections and
associated virions are observed in close contact with basement membranes of fat
body and muscle tissues, to which the eggs rapidly become attached following
introduction into the host hemocoel. We discuss the implications of this unusual
virus-chorion association in terms of immune protection, delivery of virus to
specific host tissues, and the evolution of PVs.
PMID- 9647702
TI - Observations on the presence of the peritrophic membrane in larval Trichoplusia
ni and its role in limiting baculovirus infection.
AB - Light microscopical examinations of dissected and stained peritrophic membranes
(PMs) were conducted to determine the presence or absence of this protective
structure in larvae of Trichoplusia ni, prior to and through ecdysis.
Observations of fourth- and fifth-instar larvae of T. ni from two independent
rearing colonies showed that PMs were present and lined the midgut prior to,
during, and immediately after ecdysis in both instars. Western blot analysis of
insect intestinal mucin (IIM), a major protective protein in the T. ni PM,
indicated that synthesis of IIM occurred during T. ni embryonic development, or
more precisely, that IIM synthesis started approximately 4 h prior to hatching.
These results demonstrated that the neonate T. ni midgut is lined with a
protective mucinous layer at hatching. A baculovirus enhancin from T. ni
granulosis virus (TnGV) enhanced per os viral infections of budded viruses (BVs)
of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) and T. ni
single nuclear polyhedrosis virus (TnSNPV) in neonate, fourth-, and fifth-instar
larvae of T. ni. These results provided further evidence that the PM may serve as
a partial barrier to viruses in the midgut lumen and that enhancins can
facilitate the infection process.
PMID- 9647703
TI - AcMNPV pathogenesis and developmental resistance in fifth instar Heliothis
virescens.
AB - Autographa californica M nucleopolyhedrovirus carrying a lacZ reporter gene was
used to study pathogenesis and developmental resistance in fifth instar Heliothis
virescens. Compared to fourth instar larvae, the progression of infection
proceeded much more slowly in fifth instar larvae, and developmental resistance
in orally inoculated larvae was much more sudden and severe. The resistance
occurred within the first 6 h of the fifth instar and was partially relieved by
the optical brightener M2R. Inclusion of M2R in oral inocula not only increased
mortality levels, but also increased both the percentages of insects expressing
lacZ and the numbers of foci 24 h after infection. This early developmental
resistance was not observed in insects infected intrahemocoelically, indicating
that it was mediated by the midgut and/or the tracheal system servicing the
midgut. Another less severe resistance was encountered in insects
intrahemocoelically infected 36 to 48 h postmolt. This later resistance was
partially relieved by methoprene indicating that it was, in part, hormonally
mediated. Fifth instar insects fatally infected prior to 12 h postmolt never
pupated, but pupation increasingly occurred in insects fatally infected 12 to 48
h postmolt. This pattern of larval/pupal death was consistent with viral
inactivation of the ecdysone commitment peak.
PMID- 9647704
TI - Processing of delta-endotoxin of Bacillus thuringiensis subsp. kurstaki HD-1 in
Heliothis armigera midgut juice and the effects of protease inhibitors.
AB - Bombyx mori was found to be more sensitive to the protoxins of HD-1 than
Heliothis armigera. SDS-PAGE analysis showed that a large amount of activated
toxin was yielded from protoxin by B. mori gut juice while little was yielded by
H. armigera. Further degradation of activated toxin was observed in H. armigera
midgut juice detected by SDS-PAGE. pH influenced the proteolytic activity of the
midgut juice significantly, but there was no obvious effect of pH on the
degradation of activated toxin. Specific inhibitor study revealed the presence of
trypsin, chymotrypsin, and elastase in the midgut juice. TLCK, TPCK, elastatinal
and some general serine protease inhibitors successfully prevented the excessive
degradation of protoxin in H. armigera midgut juice. Chymotrypsin inhibitors
showed strong inhibitory effects against the further degradation of activated
toxin, indicating that chymotrypsin played a major role in the process. It was
presumed that the excessive degradation of protoxin in H. armigera midgut juice
was responsible for the low sensitivity of the insect to Bt. Further study
demonstrated that the excessive degradation in vitro was triggered by SDS
treatment. However, all of the tested serine protease inhibitors expressed
synergism with protoxin against H. armigera larvae, suggesting that the excessive
degradation of protoxin may occur in vivo to some extent and may be triggered by
receptor binding of activated toxin.
PMID- 9647705
TI - Detection of a virus enhancing factor in the spheroid, spindle, and virion of an
entomopoxvirus.
AB - Spheroids, spindles, and virions of an entomopoxvirus (EPV) enhanced the
infectivity of a nuclear polyhedrosis virus (NPV) when they were perorally
administered to larvae of the armyworm, Pseudaletia separata. Spheroids and
spindles at the same dose exhibited nearly the same enhancing activity. When the
dose of spheroids or spindles was reduced 10 times, the median infectious dose of
the NPV was increased approximately 100 times. An antiserum against an enhancing
factor detected the homologous antigen in spheroids, spindles, and tissue-derived
EPV virions but not in spheroid-derived virions.
PMID- 9647706
TI - A procaryote infecting the black-lipped pearl oyster Pinctada margaritifera.
PMID- 9647707
TI - In vitro yields and in vivo activity of a polyhedrin gene-deleted and wild strain
of the nucleopolyhedrosis virus of Autographa californica.
PMID- 9647708
TI - Characterization of tissue water in Tribolium confusum parasitized by
metacestodes of Hymenolepis diminuta.
PMID- 9647709
TI - Absolute Absorption Intensities in the Fundamental nu2 and nu5 Bands of 12CH3F.
AB - The absolute strengths of 93 lines belonging to the nu2 and nu5 bands of methyl
fluoride were measured in the range of 1416-1503 cm-1 using a tunable diode-laser
(TDL) spectrometer. These experimental line intensities were obtained from the
equivalent width method. The intensities were analyzed within a dyad system,
required to account properly for the strong Coriolis coupling between nu2 and
nu5. The fit to the experimental data led to the determination of the dipole
moment derivatives partial differentialu/ partial differentialq2 and partial
differentialu/ partial differentialq5, as well as the first-order Herman-Wallis
correction in K to partial differentialu/ partial differentialq5. The intensities
were reproduced with an overall standard deviation of 1.44%, to be compared with
a mean experimental uncertainty equal to 1.58%. The values derived for the
vibrational band strengths of nu2 and nu5 are 2.124 (18) cm-2.atm-1 and 36.96 cm
2.atm-1 at 296 K, respectively. Copyright 1998 Academic Press.
PMID- 9647710
TI - Fourier Transform Infrared Spectroscopy of the First CO-Stretch Overtone Band of
13CH3OH.
AB - This paper presents a high-resolution Fourier transform infrared study of the
first CO-stretch overtone band of 13CH3OH. The spectrum has been recorded at the
Justus-Liebig University, Giebetasen, Germany on their Bruker IFS 120 HR Fourier
transform spectrometer. We have assigned parallel subbands in the torsional state
n = 0 for K values up to 6. Each individual subband has been fitted to a J(J + 1)
power series expansion in order to obtain the subband origin and the state
specific energy expansion coefficients for the first CO-stretch overtone state.
The average rotational constant B in the CO-stretch vCO = 2 state was found to be
0.768 cm-1, forming a smooth series with that of 0.777 cm-1 obtained in the vCO =
1 state and the ground state value of 0.787 cm-1. Modeling of the excited state
torsion-vibration energy level structure derived from the subband origins is then
discussed and molecular parameters in the vCO = 2 state are proposed. The value
obtained for the barrier height to internal rotation is 377.06 +/- 0.52 cm-1,
nearly indistinguishable from the value 378.65 cm-1 reported for the CO-stretch
vCO = 1 state. The vibrational energy is found to be 2020.9 +/- 1.4 cm-1. The
harmonic wavenumber for the CO-stretch vibration in 13CH3OH was calculated to be
omega = 1029.9 cm-1. The anharmonicity constant of this vibration is omegax = 6.5
cm-1, giving x = 6.3 x 10(-3). We have also observed asymmetry-induced K doubling
for the subbands of A symmetry for K values from 1 to 3 at sufficiently high J
values. The size of the splitting coefficients is similar to those observed for
the CO-stretch fundamental, with the exception of those for the K = 3A doublet,
where the observed splitting is about 18% larger than that for the ground and CO
stretch vCO = 1 states. Copyright 1998 Academic Press.
PMID- 9647711
TI - Infrared Fundamental and First Hot Bands of O12C17O Isotopic Variants of Carbon
Dioxide.
AB - Infrared spectra of 16O12C17O, 17O12C17O, and 17O12C18O in a carbon dioxide
sample enriched with oxygen-17 have been recorded with a resolution of about
0.0025 cm-1 in the regions of the fundamental bands, nu2 (600-800 cm-1) and nu3
(2200-2400 cm-1), and in the region of the "forbidden" band, nu1 (1200-1400 cm
1), using the long path difference Fourier transform spectrometer of the LPMA in
Paris. For each species, the first hot band in the 4.5-um region and two hot
bands at least in the 15-um region have been studied for the first time, and a
simultaneous reduction of wavenumbers measured in different spectral regions has
been carried out yielding new or improved spectroscopic constants. Line
intensities have been measured in the region of the nu2 and nu3 bands of
16O12C17O, and the corresponding rotationless transition dipole moments and
Herman-Wallis coefficients have been reported. Copyright 1998 Academic Press.
PMID- 9647712
TI - High-Resolution Study of the Near-Infrared A2Pi1/2-X2Sigma+ Transition of YS.
AB - A high-resolution excitation spectrum of gaseous YS has been recorded by laser
excitation spectroscopy in a supersonic molecular beam. The YS molecules were
produced by the reaction of laser-ablated yttrium atoms with CS2. The band of the
A 2Pi1/2-X 2Sigma+ transition near 750 nm was rotationally analyzed, and a set of
molecular constants is given for both electronic states. Copyright 1998 Academic
Press.
PMID- 9647713
TI - Dynamically Modified Torsional Eigenstates for Single-Top Molecules.
AB - We present a semiclassical treatment for the inclusion of kinetic energy
dependent variations in the moment of inertia for certain molecules exhibiting
internal rotational motion. The model is applied to trifluoroacetyl bromide and
the resulting dynamically modified transition energies yield an improved spectral
deviation in contrast to the rigid model. Copyright 1998 Academic Press.
PMID- 9647714
TI - Fourier Transform Spectroscopy of 18O-Enriched Carbonyl Sulfide from 1825 to 2700
cm-1
AB - We have measured the Fourier transform spectrum of carbonyl sulfide from 1825 to
2700 cm-1, using a sample enriched in both 18O (94.0%) and 17O (1.54%). A careful
calibration yields a line-position accuracy between 1.5 and 3.0 10(-5) cm-1. We
have observed and analyzed 118 infrared bands of which 93 are measured for the
first time: 55 for 18O12C32S, 20 for 18O12C34S, 11 for 18O12C33S, 1 for
18O12C36S, 12 for 17O12C32S, 4 for 17O12C34S, 2 for 17O12C33S, and 13 for
18O13C32S. Intensities are also reported and analyzed for all those bands. The
intensity accuracy is better than 10%, and the precision of approximately 1%
allows us to determine some Herman-Wallis coefficients. Copyright 1998 Academic
Press.
PMID- 9647715
TI - The B1Pi --> X1Sigma+ System of Scandium Monoiodide.
AB - Rotational analyses have been carried out on eight thermically excited emission
bands of the infrared B1Pi --> X1Sigma+ system of scandium monoiodide between
4000 to 5000 cm-1, recorded by Fourier transform spectrometry. Rotational
constants and energies are obtained for X1Sigma+ (v = 0, 1, 2) and B1Pi (v = 0-4)
levels from which equilibrium constants of the states are derived. Perturbational
effects are observed in the bands with v" = 1 that are interpreted as
consequences of the avoided crossing of X1Sigma+ (v = 1) and a3Delta1 (v = 0) at
J = 70. A treatment of the perturbation is made using an effective 2 x 2 matrix
representation of the rotational energies of the two levels. Copyright 1998
Academic Press.
PMID- 9647716
TI - Lamb-Dip Millimeter-Wave and High-Resolution Far Infrared Spectra of HCCF.
AB - The ground state rotational spectrum of fluoroacetylene was measured in the
millimeter-wave and FIR regions up to 1280 GHz and J = 65. Very accurate values
of the rotational and centrifugal distortion constants were determined and in
particular a more reliable value of H0 = 2.0 10(-4) Hz has been obtained compared
to that previously determined of -0.30 Hz. HCCF was prepared in a dc glow
discharge in presence of 1,3,5-trifluorobenzene. Copyright 1998 Academic Press.
PMID- 9647717
TI - Nuclear Quadrupole Coupling in 1,1,1-Trichloroethane: Inertial and Principal
Tensors for 35Cl and 37Cl.
AB - The hyperfine structure in the J = 1 <-- 0 and J = 2 <-- 1 transitions of
35Cl3CCH3 and 35Cl237ClCCH3 was resolved by utilizing the sub-Doppler resolution
of a pulsed supersonic beam, cavity Fourier transform microwave (FTMW)
spectrometer. The complete inertial and principal quadrupole tensors of the
chlorine nuclei are determined. The symmetric top treatment for 35Cl3CCH3 and the
asymmetric top treatment for 35Cl237ClCCH3 are found to yield identical results
for the principal tensor components of the 35Cl nucleus. The quadrupole asymmetry
parameter eta for the chlorine nuclei in 1,1,1-trichloroethane is small, which
indicates nearly cylindrical symmetry of the field gradient. Nevertheless, there
is evidence for some deviation of the z symmetry axis of the field gradient from
the direction of the C-Cl bond. Copyright 1998 Academic Press.
PMID- 9647718
TI - High-Resolution Infrared Diode Laser Spectroscopy of Ne-N2O, Kr-N2O, and Xe-N2O.
AB - The rotationally resolved spectra of the van der Waals complexes Ne-N2O, Kr-N2O,
and Xe-N2O have been investigated in the region of the nu3 N2O monomer
vibrational band using a diode laser absorption spectrometer that is incorporated
with a multipass cell and a pulsed jet. The spectra of these three complexes are
completely analyzed using a normal asymmetric rotor Hamiltonian, and the
effective molecular constants are accurately determined for both the ground and
the excited vibrational states. These results show that, like Ar-N2O, the
complexes have a T-shaped configuration in which the rare gas atom prefers to lie
near to the oxygen side of N2O. The band origins of Rg-N2O (Rg = Ne, Ar, Kr, and
Xe) are observed to shift by 0.36125, 0.15038, -0.10131, and -0.49066 cm-1 from
that of the monomer, respectively. These band origin shifts are well explained by
a simple model for the intermolecular potential. Copyright 1998 Academic Press.
PMID- 9647719
TI - The Molecular Constants and Potential Energy Curve of the Ground State X1Sigma+
in KLi.
AB - The ground state X1Sigma+ of the diatomic molecule KLi has been studied by
analyzing spectra of the B1Pi-X1Sigma+ system, simplified by polarization
labeling. Rotational and vibrational constants are reported for the X1Sigma+
state covering about 45% of its potential well depth and the potential curve is
constructed by the Rydberg-Klein-Rees (RKR) procedure. Comparison with previous
experimental and theoretical work is made. Copyright 1998 Academic Press.
PMID- 9647720
TI - Saturation Sideband CO2 Laser Spectroscopy of the Overtone Band 2nu2 and Its Hot
Band 3nu2-nu2 of Carbonyl Sulfide.
AB - The saturation spectra of the 2nu2 and the 3nu2-nu2 bands of carbonyl sulfide
have been studied using a CO2 laser sideband spectrometer. The frequency of 20
absorption lines has been determined with an accuracy of 20 kHz. These data have
been included in a global rovibrational analysis including all the other data
available on 16O12C32S. We list an improved set of standard frequencies at the
10(-6) cm-1 level. Copyright 1998 Academic Press.
PMID- 9647721
TI - Observation of TiF+ by Velocity Modulation Laser Spectroscopy and Analysis of the
AB - The molecular ion TiF+ has been observed for the first time using high-resolution
spectroscopy. The ions were produced in the positive column of an AC glow
discharge with a gas mixture of He/TiF4. A single-mode cw dye laser along with
the velocity modulation detection technique was used to record an absorption
spectrum in the spectral region 16 800-18 600 cm-1. The observed system was
assigned to the 0-0 and 1-1 bands of the [17.6]3Delta-X3Phi transition of TiF+.
The rotational analysis of the main subbands has been performed up to J values
equal to 77 and 56 for the 0-0 and 1-1 bands, respectively. Despite a careful
search, no intercombination band was observed. A set of effective molecular
parameters has been determined, characterizing the v = 0, 1 levels of the
[17.6]3Delta and X3Phi states. The spin-orbit constants Ae and the vibrational
constants omegae, omegaexe have been estimated for both electronic states, as
well as their equilibrium distances Re (1.7509 and 1.7800) A for the [17.6]3Delta
and X3Phi states, respectively). Copyright 1998 Academic Press.
PMID- 9647722
TI - Diode Laser and FTIR Spectroscopy of BrCN Isotopomers in the Region of the nu3
Band.
AB - The nu3 fundamental band (C-N stretch) and four associated hot bands (01(1)1
01(1)0, 10(0)1-10(0)0, 02(0)1-02(0)0, and 02(2)1-02(2)0) of natural 79/81Br12C14N
have been recorded and analyzed in the 4.8-um region using an FTIR spectrometer.
Analyses of the same hot bands, previously recorded using a diode laser
spectrometer, are also presented for the 13C and 15N isotopically labeled
species. Copyright 1998 Academic Press.
PMID- 9647723
TI - The nu6 + nnu9 Levels of Dicyanoacetylene.
AB - In addition to the previously observed band system nu6 + (n + 1)nu9-nnu9 with n =
0 to 7, Deltal = 0, and l = n near 611 cm-1, we have identified the nu6 + (n +
1)nu9 - (n + 2)nu9 system with n = 0 to 6, Deltal = 0, and l = n + 2 near 397 cm
1. From these bands the rovibrational levels of the states (v6, nv9) with n < 4
have been determined and spectroscopic parameters have been obtained taking into
account rotational and vibrational l-type resonances. Effective anharmonicity
constants x69 and g69 have been calculated also for levels with n >/= 4.
Copyright 1998 Academic Press.
PMID- 9647724
TI - Zeeman Tuning Rates for Q-Branch Transitions in the nu3 Band of NO2
AB - Zeeman tuning rates have been measured for Q-branch transitions in the nu3 band
of NO2 ( approximately 1610 cm-1) for magnetic fields of up to 564 Gauss. The
average measured tuning rate is 0.1815(53) x 10(-3) cm-1/Gauss with no dependence
on Ka within the approximately 3% standard deviation. Despite significant spin
rotation interaction between several of the observed levels the result agrees
with the simple linear model for Hunds case (b) molecules (tuning rate = 2uogs =
0.18696 x 10(-3) cm-1/G), which neglects the spin-rotation interaction between
different J states. The Zeeman effect is analyzed in a full treatment of the
Hamiltonian, including spin-rotation interaction, in order to account for the
agreement with 2uogs and to explore the onset of spin-rotation effects in the
spectra as the magnetic field is increased. Copyright 1998 Academic Press.
PMID- 9647725
TI - Rotational Spectrum of CD2I2
AB - The rotational spectrum of CD2I2 was measured and analyzed by combining results
from two different millimeter wave spectrometers. Low-J transitions were measured
with a free jet spectrometer at conditions of completely resolved hyperfine
structure over the frequency range 59-69 GHz. High-J rotational transitions were
measured at room temperature at frequencies 167-338 GHz and for J" up to 190".
Spectroscopic constants in the sextic rotational Hamiltonian of CD2I2 have been
determined, and the analysis of the observed hyperfine structure yielded all
components in the inertial and in the principal nuclear quadrupole coupling
tensors for the iodine nuclei. The rotational constants for CD2I2 and those for
CH2I2 from Z. Kisiel, L. Pszczolkowski, W. Caminati, and P. G. Favero (1996. J.
Chem. Phys. 105, 1778-1785) have been used to evaluate a full r0 structure and
have been combined with the results of ab initio calculations to also evaluate
the average r* structure: r(CI) = 2.1364 A, r(CH) = 1.078 A, <(ICI) = 113.83
degrees, and <(HCH) = 113.3 degrees. The current results complete the first
analysis of a rotational spectrum of a molecule containing two iodine nuclei.
Copyright 1998 Academic Press.
PMID- 9647726
TI - Water Vapor Line Assignments in the Near Infrared.
AB - The high-resolution spectrum of water vapor between 13 200 and 16 500 cm-1
recorded by J.-Y. Mandin, J-P. Chevillard, C. Camy-Peyret, J.-M. Flaud, and J. W.
Brault (1986. J. Molec. Spectrosc., 116, 167) is analyzed using high-accuracy
linelists obtained using ab initio calculations and spectroscopically determined
potential. Assignments to H216O transitions are presented for 663 of the 795
unassigned lines presented in the original paper. In addition, 38 lines are
reassigned. The majority of these assignments and reassignments are confirmed by
combination differences. These assignments significantly extend the measured data
for the 4nu and 4nu + delta polyads and provide the first information on the
(240), (033), (160), (170), and (071) bands. It is likely that a significant
fraction of the remaining unassigned lines belong to H218O. Copyright 1998
Academic Press.
PMID- 9647729
TI - Molecular biology of the proteasome.
AB - The proteasome is an unusually large multisubunit proteolytic complex, consisting
of a central catalytic machine (equivalent to the 20S proteasome) and two
terminal regulatory subcomplexes, termed PA700 or PA28, that are attached to both
ends of the central portion in opposite orientations to form the enzymatically
active proteasome. Totally about 40 subunits with sizes of 20-110 kDa are
assembled to form two types of the proteasomal complexes with the same catalytic
core and different regulatory modules. To date, cDNAs or genes encoding almost
all subunits of human and the budding yeast proteasomes have been isolated by
molecular-biological techniques. In this minireview, I summarize briefly
available information on the structure-function relationships of the proteasome
acting as a protein death machinery.
PMID- 9647730
TI - Basophilic differentiation of the human leukemia cell line KU812 upon treatment
with interleukin-4.
AB - The human leukemia cell line KU812 had been described as an immature
prebasophilic cell line and exhibits a potential to differentiate into mature
basophils. We studied the effect of interleukin-4 (IL-4) on the basophilic
differentiation of KU812 cells. When KU812 cells were cultured with 1 ng/ml IL-4,
cellular histamine content increased more than 10-fold. IL-4 also enhanced the
expression of Fc epsilon RI alpha, a high affinity IgE receptor, on the cell
surface. KU812 cells treated with IL-4 expressed higher levels of Fc epsilon RI
alpha, Fc epsilon RI beta and Fc epsilon RI gamma mRNA than non treated KU812
cells. After 21 days in culture with IL-4, KU812 cells became morphologically
mature basophilic cells as demonstrated by staining positive for cytoplasmic
granules and heparin proteoglycan by Wright dye and toluidin blue dye
respectively. In addition, IgE-mediated histamine release was observed,
suggesting that the Fc epsilon RI induced by IL-4 was functional and was able to
transduce a signal for degranulation. These results suggest that IL-4 promotes
differentiation of KU812 cells into mature basophilic cells both morphologically
and functionally.
PMID- 9647731
TI - Replication of lambda plasmid DNA in the Escherichia coli cell cycle.
AB - The Cro repressor autoregulatory loop has long been considered the main
regulatory process in controlling lambda plasmid replication initiation in
Escherichia coli. However, we found recently that lambda plasmids can be
maintained at a constant copy number in the absence of Cro function. Here we
demonstrate that shortly after inactivation of the Cro repressor, the synthesis
of lambda plasmid DNA increases significantly but is then stabilized at a level
similar to that observed in the presence of the Cro function. We found that
replication initiation of lambda plasmids carrying a functional cro gene proceeds
randomly in the host cell cycle, but in the absence of Cro function the
replication initiation of lambda plasmid DNA appears to be cell cycle dependent.
The host DnaA protein appears to be at least one of the factors involved in the
cell-cycle-specific control of lambda cro- plasmid replication. Therefore, it
seems that the lambda cro- plasmid may serve as an amazingly simple model for
studies on the regulation of DNA replication in the cell cycle.
PMID- 9647732
TI - STAT3 forms stable homodimers in the presence of divalent cations prior to
activation.
AB - We present evidence that the transcription factor STAT3, derived from uninduced
cells, can form stable homodimers, which are independent of the tyrosine
phosphorylation status of the protein. The strong interaction, which is resistant
to many denaturing agents, is dependent on the presence of divalent cations. The
presence of the homodimer was initially observed in immunoprecipitates of STAT3
and was detected upon fractionation of cell lysates. These dimers are different
in structure from dimers observed after cytokine stimulation of cells, which
results in tyrosine phosphorylation of STAT3 and dimerization involving the SH2
domain of STAT3.
PMID- 9647733
TI - Thyroid status and the regulation of thyrotropin-releasing hormone synthesis in
rat pancreatic islets: comparison with insulin regulation.
AB - Thyrotropin-releasing hormone (TRH), originally characterized as the first
hypothalamic hormone, is also synthesized in the insulin-containing cells. TRH
stimulates the glucagon secretion and attenuates exocrine pancreatic secretions.
We have previously reported, using whole pancreatic homogenates, that TRH content
increased in hypothyroid rats, associated to a loss of TRH-degrading activity.
The present study was undertaken on purified islets, an appropriate model to
examine thyroid status-dependent regulation of two islet hormones, TRH and
insulin. The islets from hypothyroid rat pancreas had increased TRH content (4x)
without any change in insulin content. Likewise, the Northern blot analysis
revealed that the steady-state concentrations of TRH mRNA increased (4x) while
those of insulin remain unchanged. These data therefore suggest that TRH gene
transcription is under the negative control of T3. This study also provides
insight into islet response to impaired thyroid function.
PMID- 9647734
TI - Kell and Kx, two disulfide-linked proteins of the human erythrocyte membrane are
phosphorylated in vivo.
AB - Kell and Kx are two quantitatively minor proteins from the human erythrocyte
membrane which carry blood groups antigens and are thought to be a
metalloprotease and a membrane transporter, respectively. In the red cell
membrane, these proteins form a complex stabilized by disulfide bond(s).
Phosphorylation status of these proteins was studied, in the presence or absence
of effectors of several kinases, either on intact cells incubated with [32P]
orthophosphate or on ghosts incubated with [gamma-32P]ATP. Purification of Kell
Kx complex, by immunochromatography on an immobilized human monoclonal antibody
of Kell blood group specificity allowed to establish that (i) neither protein is
phosphorylated on tyrosine; (ii) the Kell protein is a putative substrate for
Casein Kinase II (CKII) and Casein Kinase I (CKI) but not for protein kinase C
(PKC), whereas Kx protein is phosphorylated by CKII and PKC but not by CKI; (iii)
Protein Kinase A neither phosphorylates the Kell nor the Kx proteins.
PMID- 9647735
TI - The first caldesmon-like protein in higher plants.
AB - Using anti-caldesmon polyclonal and monoclonal (raised against the N-terminal
fragment of chicken gizzard caldesmon) antibodies, a plant caldesmon-like
protein, 107 kDa as determined by SDS-gel electrophoresis, has been identified
based on Western blotting of total extracts of Ornithogalum virens pollen tubes.
Biochemical investigations showed common properties of this protein with animal
caldesmon--it binds to actin and, in a Ca(2+)-dependent manner, to calmodulin. In
contrast to animal caldesmon, this plant cell counterpart is relatively resistant
to proteolysis by endogenous proteases and sensitive to heat treatment. Our
results show the presence of a caldesmon-like protein in higher plants for the
first time.
PMID- 9647736
TI - Structural characterization and mapping of the normal epithelial cell-specific 1
gene.
AB - The normal epithelial cell-specific 1 (NES1) gene is a recently identified novel
serine protease-like gene which is down-regulated during breast cancer
progression. The gene product has 34-42% identity with the members of three
distinct serine protease families: the trypsin-like family, activators of kringle
domain-containing growth factors, and the kallikrein family (X. L. Liu et al.,
(1996) Cancer Res 56, 3371-3379). Although the cDNA of this gene has been cloned,
its genomic structure and chromosomal position are not as yet known. Here, we
report the genomic characterization and mapping of the NES1 gene. By subcloning
and sequencing a PAC clone containing the complete NES1 gene, we were able to
characterize the structure of this gene. The NES1 gene spans 5.5 kb and is
composed of five coding exons and one untranslated exon. The positions of the
introns were similar to trypsinogen, prostate specific antigen (PSA), and tissue
plasminogen activator (TPA). NES1 gene was also localized with somatic cell
mapping, radiation hybrid mapping, and fluorescence in situ hybridization
techniques to chromosome 19q13.3-q13.4, the same region where the human
kallikrein gene family resides. Taken together, our results suggest that the NES1
gene originates from the same ancestor as trypsinogen, PSA, and TPA, but remains
in close proximity to PSA.
PMID- 9647737
TI - Purification from human plasma of a hexapeptide that potentiates the sulfation
and mitogenic activities of insulin-like growth factors.
AB - The human plasma contains small peptide molecules known as low molecular weight
growth factors synergistically increasing certain biological actions of insulin
like growth factors. In the present work we isolated and characterized a
hexapeptide with HWESAS as structure. This purified peptide was absolutely
necessary for the sulfation activity of insulin-like growth factor-I on chick
embryo pelvic cartilages and improved the mitogenic activity of both insulin-like
growth factors. The effects of this hexapeptide were confirmed by using the
homologous synthetic peptide, that exhibited similar biological effects. Other
synthetic peptides with structure derived from hexapeptide were shown to be
active: the pentapeptide HWESA appeared more potent than the tripeptide HWE,
which is about 170 to 200 times less active than the hexapeptide. The sequence of
hexapeptide HWESAS is identified in only one human protein that is C3f, a
fragment of C3 complement.
PMID- 9647738
TI - Formation of fluorescent heme degradation products during the oxidation of
hemoglobin by hydrogen peroxide.
AB - Hemoglobin and methemoglobin oxidized by hydrogen peroxide generate
ferrylhemoglobin and oxoferrylhemoglobin, respectively. Two fluorescent compounds
were found to be produced during the reaction of oxyhemoglobin, but not
methemoglobin, with H2O2. These two compounds had excitation wavelengths of 321
nm and 460 nm, respectively, with emission wavelengths of 465 nm and 525 nm,
respectively. The formation of the same fluorescent products during the reaction
of H2O2 with ferroprotoporphyrin-IX and ferriprotoporphyrin-IX demonstrate that
these compounds originate from the heme moiety. The release of heme iron during
the formation of these fluorescent compounds indicates that they are associated
with heme degradation. The time course for the formation of fluorescent products
show that the extent of heme degradation is dependent on H2O2 concentration. The
results of this investigation indicate that the heme moiety of Fe(II) hemoglobin
undergoes degradation in presence of H2O2. The ability to detect this process by
fluorescence provides a sensitive marker in order to asses hemoglobin and RBC
oxidative stress under pathological conditions.
PMID- 9647739
TI - Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing
protein that interacts with BAI1.
AB - Brain-specific angiogenesis inhibitor 1 (BAI1), which is a p53-target gene
specifically expressed in brain, encodes a seven-span transmembrane protein.
Using a two-hybrid system, we isolated a cDNA that encodes a protein, named BAP1
(BAI1-associated protein), which interacts with the cytoplasmic region of BAI1.
BAP1 is a novel member of the MAGUK (membrane-associated guanylate kinase
homologue) family; it possesses a guanylate kinase domain, WW domains, and
multiple PDZ domains. Interaction between BAI1 and BAP1 was mediated by a QTEV
motif in the carboxy-terminal region of BAI1 and PDZ domains of BAP1. By
immunocytochemical analysis of COS-7 cells transfected with BAI1 and BAP1, both
products were co-localized at the cytoplasmic membrane, especially at cell-cell
junctions. Cells transfected with BAI1 formed filopodia-like cytoplasmic
extensions. These results suggest that BAI1 and BAP1 might be involved in cell
adhesion and signal transduction in brain.
PMID- 9647740
TI - Stimulatory effect of endogenous tissue inhibitor of metalloproteinases-1 (TIMP
1) overexpression on type IV collagen and laminin gene expression in rat mammary
carcinoma cells.
AB - We recently reported enhanced tumor growth and stimulation of vascular
endothelial growth factor (VEGF) expression in rat mammary carcinoma cells
transfected with a human tissue inhibitor of metalloproteinases-1 (hTIMP-1) cDNA
(1). In the present study, we examined if the composition of the stroma was
altered in the tumors with the highest hTIMP-1 production. Immunohistological
examination revealed increased amounts of the basement membrane (BM) components,
type IV collagen and laminin, in the hTIMP-1 overexpressing tumors compared to
that of the control. In vitro studies also revealed upregulation of type IV
collagen and laminin gene expression associated with the hTIMP-1 overexpression.
Endogenous RNA levels of rat TIMP-1 and the rat matrix metalloproteinases (MMPs),
MMP-2, MMP-3, and MMP-9, were not affected by the hTIMP-1 transfection,
suggesting that the increase in BM deposition was not a result of decreased
collagenolytic activity. This is the first report to show an association between
overexpression of TIMP-1 and increased tumor BM matrix production through
stimulation of type IV collagen and laminin gene expression.
PMID- 9647741
TI - Severe osteoporosis in mice lacking osteoclastogenesis inhibitory
factor/osteoprotegerin.
AB - Osteoclasts are multinucleated cells that resorb bone. Osteoclastogenesis
inhibitory factor (OCIF), also called osteoprotegerin (OPG), acts as a naturally
occurring decoy receptor for osteoclast differentiation factor, which mediates an
essential signal to osteoclast progenitors for their differentiation into
osteoclasts. Here we show that the OCIF/OPG knockout mice exhibited severe
osteoporosis due to enhanced osteoclastogenesis when they grew to be adults.
These mice were viable and fertile. They exhibited marked bone loss accompanied
by destruction of growth plate and lack of trabecular bone in their femurs. The
strength of their bones dramatically decreased. These results demonstrate that
OCIF/OPG is a key factor acting as a negative regulator against
osteoclastogenesis. The OCIF/OPG knockout mice provide the first animal model for
osteoporosis without other obvious abnormalities.
PMID- 9647742
TI - 2-Methoxyestradiol-induced phosphorylation of Bcl-2: uncoupling from JNK/SAPK
activation.
AB - The natural estrogen metabolite 2-methoxyestradiol (2ME) is anti-angiogenic in
vivo and a strong growth inhibitor in vitro. The growth inhibition is due to
mitotic arrest and apoptosis. These effects are reminiscent of those induced by
taxol, and appear to be mediated by inhibition of microtubule dynamics. Here we
have studied the cellular response to 2ME in regard to potential mediators of the
observed cellular changes. 2ME treatment increases the insoluble polymerized
fraction of cellular tubulin similar to taxol, and in contrast to the microtubule
depolymerizing drugs such as colcemid and vincristine. This stabilization
following 2ME treatment is accompanied by phosphorylation and inactivation of Bcl
2 increasing gradually from 2-24 hours. To study the pathway leading to Bcl-2
phosphorylation we analyzed Raf-1 and JNK/SAPK kinases, both of which have been
reported to be involved in Bcl-2 inactivation. Our results indicate that Raf-1 is
phosphorylated in response to 2ME, but this occurs later than Bcl-2
phosphorylation suggesting that Raf-1 is not directly phosphorylating Bcl-2.
JNK/SAPK was activated rapidly after 2ME treatment. However, this activation was
transient and returned to undetectable levels by 2 hours of treatment,
demonstrating that JNK/SAPK is not directly phosphorylating Bcl-2. Taken together
with previous results indicating that overexpression of JNK/SAPK leads to Bcl-2
phosphorylation, our results would support a model where JNK/SAPK is indirectly
phosphorylating Bcl-2.
PMID- 9647743
TI - Requirement of corepressor binding of thyroid hormone receptor mutants for
dominant negative inhibition.
AB - Resistance to thyroid hormone (RTH) is mainly caused by dominant negative
inhibition of wild type thyroid hormone receptor (TR) function due to mutations
in the ligand binding domain of the TR beta. Because no RTH mutant was identified
in the hinge region of the TR, the contribution of this region for dominant
negative inhibition was explored. In transient transfection assays, the dominant
negative activity of a RTH-type mutant (P453X) was abolished by an introduction
of a mutation into the hinge region (P214R). Although this hinge mutation did not
alter homo- or heterodimerization with retinoid X receptor (RXR), its association
with nuclear receptor corepressor (N-CoR) was impaired. These results indicate
that association of corepressor with the RTH mutants through the hinge region is
crucial for their dominant negative activity.
PMID- 9647744
TI - Superoxide production in human neutrophils: evidence for signal redundancy and
the involvement of more than one PKC isoenzyme class.
AB - Selective protein kinase C (PKC) activators and inhibitors and a physiological
agonist, fMLP, were used to study superoxide production and PKC isoenzyme
activation in human neutrophils. The data show that the classical PKC isoenzymes,
alpha and beta, were activated by TPA and at a time prior to NADPH oxidase
complex assembly. fMLP induced activation of PKC-beta over a similar time course.
Inhibition of c-PKCs reduced, but did not block, TPA-induced superoxide
production completely, suggesting additional PKC isoenzymes were involved beyond
NADPH oxidase assembly. PKC inhibitors were unable to inhibit fMLP-induced
superoxide generation, indicative of signal redundancy in the induction of
superoxide generation in human neutrophils.
PMID- 9647745
TI - Evidence for role of phospholipase A2 in phosphatidic acid-induced signaling to c
fos serum response element activation.
AB - The activity of exogenous phosphatidic acid (PA) to transactivate c-fos serum
response element (SRE) was investigated by transient transfection analysis.
Incubation of Rat-2 fibroblast cells with exogenous PA caused a stimulation of c
fos SRE-linked luciferase activity in a dose- and time-dependent manner. The SRE
stimulation by PA was dramatically reduced by either pre-treatment with
mepacrine, an inhibitor of phospholipase A2 (PLA2), or co-transfection with
antisense cytosolic phospholipase A2 (cPLA2) oligonucleotide, whereas
lysophosphatidic acid (LPA)-induced SRE activation was not affected. Consistent
with this specific requirement for PLA2 by PA, the translocation of cPLA2 protein
was rapidly induced followed by PA treatment. Together, these results suggest
that PLA2, especially cPLA2, plays a critical role in the nuclear signaling
cascade of PA in Rat-2 fibroblast cells.
PMID- 9647746
TI - Molecular characterization of a 28 kDa surface antigen gene family of the tribe
Ehrlichiae.
AB - Antisera against different Ehrlichiae recognize an immunodominant, cross-reacting
approximately 28 kDa surface antigen defined as the MAP1 in Cowdria ruminantium.
These antigens are considered valuable in developing serodiagnostic tests and
recombinant vaccines for Ehrlichiae infections. To evaluate the relationship in
three closely related Ehrlichiae, Ehrlichia chaffeensis, Ehrlichia canis, and C.
ruminantium, the structure of the 28 kDa antigen genes was analyzed. We describe
the cloning and characterization of DNA encoding genes homologous to MAP1 from E.
chaffeensis and E. canis. The cloned segment of E. chaffeensis contains one
expressed and four transcriptionally silent tandemly arranged, nonidentical
genes; the E. canis locus consists of two nonidentical genes. Comparative
analysis of these genes revealed the presence of four conserved regions separated
by three highly variable regions. B-cell epitope analysis identified three major
cross-reacting epitopes that map to the variable regions. Location of the
epitopes at the variable regions and the presence of multigene family with only
one expressed copy suggest a mechanism of immune evasion in these Ehrlichiae.
PMID- 9647747
TI - Comparative expression of novel vascular endothelial growth factor/vascular
permeability factor transcripts in skin, papillomas, and carcinomas of v-Ha-ras
Tg.AC transgenic mice and FVB/N mice.
AB - One of the most frequently detected changes in human solid tumors is the mutation
of the ras oncogene, which has been associated with production of angiogenic
growth factors such as vascular endothelial growth factor/vascular permeability
factor (VEGF/VPF). Using the v-Ha-ras Tg-AC transgenic mice and the background
FVB/N strain of inbred mice, the pattern of expression of specific VEGF/VPF
transcripts was characterized in major organs and in skin, papillomas, and
carcinomas during multi-stage skin carcinogenesis. Three VEGF/VPF transcripts
were found to be constitutively expressed in skin as well as the major organs in
both mouse strains, which corresponded in size and sequence to previously
reported murine VEGF120 with a bp size of 331, VEGF164 with a bp size of 333, and
VEGF188 with a bp size of 407. A previously unreported fourth murine transcript
was also detected in skin and major tissues from both mouse strains which
corresponded to rat VEGF144, with a bp size of 404. In addition, a unique 425 bp
VEGF transcript which corresponded to human VEGF205 was present in highly
vascularized tissues including heart, lung, liver, kidney, brain, as well in
papillomas and carcinomas isolated from v-Ha-ras Tg.AC mice. In contrast, VEGF205
was present only in carcinomas derived from FVB/N mice. An antibody generated
from a peptide sequence designed to detect each of the five VEGF/VPF peptides
defined by RT-PCR analysis confirmed the existence of these five peptides and
confirmed that the murine VEGF205 peptide was selectively expressed in papillomas
and carcinomas derived from v-Ha-ras Tg.AC mice. These results demonstrate that
there is significant alternative splicing of the murine VEGF/VPF gene during
multi-stage carcinogenesis, which results in four commonly expressed VEGF
transcripts. In addition, these studies identified a fifth VEGF transcript and
peptide at the later stages of tumor promotion and in progression which appears
to be linked to the presence of v-Ha-ras.
PMID- 9647748
TI - Interaction of free fatty acids with human leptin.
AB - Relatively high concentrations of leptin are present in plasma and it is thought
to play a major role in lipid homeostasis. Leptin is reported to lower tissue
triglyceride content by increasing intracellular oxidation of free fatty acids
(FFA). However very little is known regarding the interaction between leptin and
plasma FFA. We studied the interaction of FFA with leptin using a direct
radiolabelled fatty acid binding assay, a fluorescence assay, electrophoretic
mobility and autoradiobinding. All these data indicate that binding of FFA with
leptin is reversible and shows a positive co-operativity. The binding of FFA to
leptin produces a change in the pI value of the leptin and also increased the
electrophoretic mobility of the protein in native polyacrylamide gels. The change
in leptin's electrophoretic mobility depends on the chain length and the number
of double bonds of the fatty acid, as stearic acid, 18:0, had no effect whereas
oleic acid, 18:1n-9, linoleic acid, 18:2n-6, arachidonic acid, 20:4n-6, and
docosahexaneoic acid, 22:6n-3, affected leptin's mobility to different degrees.
The physiological implication of leptin-FFA interaction is not known, however the
interaction may depend on the plasma FFA composition and concentration which are
known to vary in different pathological/physiological conditions.
PMID- 9647749
TI - Peroxide reductase activity of NADH dehydrogenase of an alkaliphilic Bacillus in
the presence of a 22-kDa protein component from Amphibacillus xylanus.
AB - The NADH oxidase of Amphibacillus xylanus shows high NADH-peroxide reductase
activity for hydrogen peroxide and alkyl hydroperoxides in the presence of a 22
kDa disulfide-containing protein component (Y. Niimura, L. B. Poole, and V.
Massey, J. Biol.Chem. 270, 25645-25650, 1995). It was found that the membrane
bound NADH dehydrogenase of an alkaliphilic Bacillus (YN-1) involved in the
respiratory chain also exhibits reductase activity for hydrogen peroxide and
cumene hydroperoxide in the presence of the 22-kDa component from Amphibacillus
xylanus. Vmax values for these substrates were as high as those of the NADH
oxidase of A. xylanus. Although the 38-kDa protein produced by trypsin treatment
of NADH dehydrogenase retains NADH dehydrogenase activity, it exhibited no
peroxide reductase activity in the presence of the 22-kDa component from A.
xylanus. The NADH dehydrogenase of YN-1 might not only catalyze electron flow
from NADH to the respiratory chain, but also function for scavenging peroxide.
PMID- 9647750
TI - Differential deficiency of mevalonate kinase and phosphomevalonate kinase in
patients with distinct defects in peroxisome biogenesis: evidence for a major
role of peroxisomes in cholesterol biosynthesis.
AB - Peroxisomes catalyze a number of essential metabolic functions especially related
to lipid metabolism. There is increasing evidence suggesting that peroxisomes are
also involved in the synthesis of isoprenoids via the mevalonate pathway at least
in rat liver. In order to obtain independent evidence for a role of peroxisomes
in isoprenoid synthesis in man, we have measured the activity of two key enzymes
of the mevalonate pathway in patients suffering from certain defined defects in
peroxisome biogenesis. We now report that mevalonate kinase is not only deficient
in livers from Zellweger patients in which peroxisome biogenesis is defective,
but also in livers from rhizomelic chondrodysplasia punctata (RCDP) Type 1
patients. In the latter group of patients there is a selective defect in
peroxisome biogenesis due to a genetic defect in the PTS2-receptor, a mobile
receptor-protein guiding peroxisomal proteins with a certain peroxisomal
targeting signal (PTS2) to the peroxisome. Phosphomevalonate kinase was found to
be strongly deficient in Zellweger patients thus suggesting that this enzyme is
also peroxisomal. Taken together, our data indicate that in human liver
mevalonate kinase and phosphomevalonate kinase are truly peroxisomal enzymes
which strongly suggests that peroxisomes play a major role in cholesterol
biosynthesis.
PMID- 9647751
TI - pICln predominantly localizes at luminal surface membranes of distal tubules and
Henle's ascending limbs.
AB - We produced a highly specific antibody to the C-terminal peptide sequence of
pICln. It recognized pICln with a 38-kDa molecular mass on SDS-polyacrylamide gel
electrophoresis, coinciding with that previously reported. During native
polyacrylamide gel electrophoresis, three immunoreactive bands (38, 70, and 130
kDa) were detected. The isoelectric point of pICln was calculated to be 4.0.
Subcellular localization study showed the presence of pICln in the soluble and
microsomal fraction. pICln can be easily solubilized from the membrane fraction
with Triton X-100. From immunohistochemical observations, we found pICln to be
obviously located on the luminal surface membranes of the distal tubules and
Henle's loop ascending limbs, and it can also be found inside proximal tubular
cells. The present results suggested that pICln functions as a "cytosolic anchor
= membrane insertion" model, and it plays important roles in the "urine dilution
segment" cells of nephrons.
PMID- 9647752
TI - Determinants of recombinant production of antimicrobial cationic peptides and
creation of peptide variants in bacteria.
AB - Cationic peptides possessing antibacterial activity are virtually ubiquitous in
nature, and offer exciting prospects as new therapeutic agents. We had previously
demonstrated that such peptides could be produced by fusion protein technology in
bacteria and several carrier proteins had been tested as fusion partners
including glutathione-S-transferase, S. aureus protein A, IgG binding protein and
P. aeruginosa outer membrane protein OprF. However these fusion partners, while
successfully employed in peptide expression, were not optimized for high level
production of cationic peptides (Piers, K., Brow, M. L., and Hancock, R. E. W.
1993, Gene 137, 7-13). In this paper we took advantage of a small replication
protein RepA from E. coli and used its truncated version to construct fusion
partners. The minimal elements required for high level expression of cationic
peptide were defined as a DNA sequence encoding a fusion protein comprising, from
the N-terminus, a 68 amino acid carrier region, an anionic prepro domain, a
single methionine and the peptide of interest. The 68 amino acid carrier region
was a block of three polypeptides consisting of a truncated RepA, a synthetic
cellulose binding domain and a hexa histidine domain. The improved system showed
high level expression and simplified downstream purification. The active peptide
could be yielded by CNBr cleavage of the fusion protein. This novel vector was
used to express three classes of cationic peptides including the alpha-helical
peptide CEMA, the looped peptide bactenecin and the extended peptide indolicidin.
In addition, mutagenesis of the peptide gene to produce peptide variants of CEMA
and indolicidin using the improved vector system was shown to be successful.
PMID- 9647753
TI - Molecular cloning, expression, and functional characterization of novel mouse
sulfotransferases.
AB - Nucleotide sequences of two mouse cDNAs encoding new sulfotransferase enzymes
were determined. Analysis of the deduced amino acid sequences revealed that one
represents a novel member of the phenol sulfotransferase family and the other is
highly homologous to human SULT2B1 hydroxysteroid sulfotransferases. The
recombinant enzymes, transiently expressed in COS-7 cells, were characterized
with respect to their substrate specificity using a variety of substrates for
different types of sulfotransferases. The tissue-specific expression of these two
new mouse sulfotransferases was examined by Northern blot analysis.
PMID- 9647754
TI - The bilirubin-binding motif of bilitranslocase and its relation to conserved
motifs in ancient biliproteins.
AB - In the primary structure of bilitranslocase, currently under study in our
laboratory, an aminoacid motif was identified and found to be conserved in a
number of alpha-phycocyanines, ancient biliproteins present in cyanobacteria. To
test the possibility that such a motif could be at least part of the binding site
for bilirubin, epitope-specific antibodies were raised. The target corresponds to
the sequence 65-75 of bilitranslocase and covers the central portion of the motif
identified. The antibodies were shown: 1) to inhibit the electrogenic BSP
transport by plasmamembrane vesicles; 2) to react with purified bilitranslocase;
and 3) to identify only one protein band with electrophoretic mobility identical
to bilitranslocase in Western blots of solubilised plasmamembrane vesicles. The
presence of either bilirubin or nicotinate during pre-incubation with the
antibodies decreases concentration-wise the inhibition kinetics. From these
experiments a dissociation constant of 2.2 +/- 0.3 and 11.3 +/- 1.3 nM for
bilirubin-bilitranslocase and nicotinate-bilitranslocase complexes were
calculated.
PMID- 9647755
TI - Role of ultraviolet A-induced oxidative DNA damage in apoptosis via loss of
mitochondrial membrane potential and caspase-3 activation.
AB - UVA has been implicated in multistage photocarcinogenesis. HPLC analysis revealed
that the 7,8-dihydro-8-oxo-2'-deoxyguanosine content of DNA in HL-60 cells
increased immediately after UVA irradiation. Pulsed field gel electrophoresis
showed that cellular DNA strand breakage was induced at 1 h after UVA
irradiation. Flow cytometry showed that mitochondrial membrane potential (delta
psi m) decreased time-dependently in cells exposed to UVA. The activity of
caspase-3 and DNA ladder formation increased at 2 h after UVA irradiation. These
results suggest that UVA irradiation induces oxidative DNA damage, followed by
the loss of delta psi m and subsequent activation of caspase-3, resulting in
apoptosis.
PMID- 9647756
TI - Hammerhead ribozymes against gamma-glutamylcysteine synthetase mRNA down-regulate
intracellular glutathione concentration of mouse islet cells.
AB - gamma-Glutamylcysteine synthetase (gamma-GCS) is a key enzyme in glutathione
synthesis and is thought to play a significant role in intracellular
detoxification systems. To specifically suppress gamma-GCS gene expression, we
constructed two different hammerhead ribozymes against gamma-GCS mRNA
transcripts. Two cleavage sites were targeted as follows: site 1 for anti-gamma
GCS ribozyme (H), a GUU triplet located from +348 to +350 of the gamma-GCS heavy
chain, and site 2 for anti-gamma-GCS ribozyme (L), a GUU triplet located from
+235 to +237 of the gamma-GCS light chain. The anti-gamma-GCS ribozymes
effectively cleaved gamma-GCS mRNA in a cell-free system. When transfected into a
Min-6 mouse islet cell line, these anti-gamma-GCS ribozymes not only suppressed
gamma-GCS gene expression, but also reduced intracellular glutathione
concentration. These results suggest that the ribozyme-mediated down-regulation
of gamma-GCS gene expression may be useful for analyzing the glutathione
associated cellular defense systems of pancreatic islet cells.
PMID- 9647757
TI - Characterization of two UDP glucuronosyltransferases that are predominantly
expressed in human colon.
AB - The liver and gastrointestinal tract are major sites of drug metabolism. However,
although the UDP glucuronosyltransferase family of drug-metabolizing enzymes has
been extensively characterized in the liver, little is known about this family in
the gastrointestinal tract. In this work, an analysis of human colon RNA samples
revealed the presence of two UDP glucuronosyltransferase forms that could not be
detected in human liver. The cDNA encoding these two forms, UGT1A8 and UGT1A10,
was synthesized and expressed in COS-7 cells. Both proteins have molecular masses
of 56 kDa and are active towards hydroxylated metabolites of the carcinogens,
benzo(alpha)pyrene and 2-acetylaminofluorene. UGT1A8 was most active towards the
10- and 11-hydroxy benzo(alpha)pyrenes and the preferred 2-acetylaminofluorene
metabolites were the 1-, 2-, and 8-hydroxy derivatives. UGT1A10 was most active
towards the 11- and 12-hydroxybenzo(alpha)pyrenes and the 1- and 3-hydroxy
derivatives of 2-acetylaminofluorene. Both enzymes were inactive towards the
benzo(alpha)pyrene trans 4, 5 and 7, 8 dihydrodiols. In addition, these UDP
glucuronosyltransferases displayed differential activity towards several phenolic
substrates. A survey of human tissues indicated that UGT1A8 and UGT1A10
transcripts are predominantly expressed in the gastrointestinal tract, in
contrast to most other UDP glucuronosyltransferase forms which are expressed in
the liver and other tissues. These results suggest that UGT1A8 and UGT1A10 may
play an important role in the metabolism of dietary xenobiotics.
PMID- 9647758
TI - Identification of a novel isoform of microphthalmia-associated transcription
factor that is enriched in retinal pigment epithelium.
AB - Mutations at the mouse locus encoding microphthalmia-associated transcription
factor (Mitf) affect the development of many cell types, including retinal
pigment epithelium (RPE), melanocytes, mast cells, and osteoclasts. Here we have
identified a novel Mitf isoform, Mitf-a, and its human homologue MITF-A by cDNA
cloning. MITF-A consists of 520 amino acid residues and differs in the amino
terminus from authentic melanocyte-type MITF (MITF-M). MITF-A mRNA is widely
expressed and represents a predominant MITF isoform in cultured RPE cells,
whereas MITF-M mRNA is exclusively expressed in melanocytes and melanoma cells.
In situ hybridization analysis suggested that Mitf-a mRNA is enriched in the
prospective RPE of mouse embryo. Moreover, transient cotransfection assays
suggested that MITF-A activated transcription of the tyrosinase and tyrosinase
related protein 1 genes. MITF-A/Mitf-a therefore may play an important role in
melanogenesis in RPE.
PMID- 9647759
TI - A regulatory role of sulfhydryl groups in modulation of sperm membrane
conformation by heavy metals: sulfhydryl groups as markers for infertility
assessment.
AB - Sperm membrane sulfhydryl groups, when masked by heavy metals like cobalt and
copper at very low concentration (10(-9)) shows inhibition of lipid peroxidation
and superoxide dismutase activity. Inhibition of lipid peroxidation is suggested
to lead to reduction in membrane fluidity, a prerequisite for normal sperm
function. Augmentation of lipid peroxidation by pentoxifylline in oligospermia
provides evidence to this hypothesis that membrane sulfhydryls play a regulatory
role in membrane modulation. It is therefore suggested that these sulfhydryl
groups can be used as a tool for infertility assessment in unexplained male
infertility.
PMID- 9647760
TI - Reduction of 4-hydroxynonenal and 4-hydroxyhexenal by retinal aldose reductase.
AB - Aldose reductase has been purified to homogeneity from bovine retina. It has an
apparent molecular weight of 32,000 daltons and shares immunological and kinetic
properties with the much studied aldose reductases purified from various sources.
Retinal aldose reductase displays a K(m) of approximately 40 microM with 4
hydroxynonenal and 4-hydroxyhexenal, the oxidation end products of arachidonic
and docosahexanoeic acids, respectively. It therefore appears that aldose
reductase may constitute a major detoxification route of these toxic aldehydes in
the retina.
PMID- 9647761
TI - Structural variations in nisin associated with different membrane mimicking and
pH environments.
AB - Nisin is a membrane active antimicrobial peptide containing unusual dehydrated
amino acid residues. The secondary structure of nisin in aqueous solution,
membrane mimicking solvents and at various pH values was investigated using
circular dichroism. In aqueous solution nisin is largely randomly coiled. In
liposomes and at pH 6 and above, however, the presence of a maximum at 195 nm and
a minimum at 190 nm was notable and indicative of beta-turn formation in these
environments. This change in structure was speculated to result in an increasing
unavailability of the site for initial reaction of peptide and membrane at higher
pH.
PMID- 9647762
TI - Identification of cDNAs induced by the tumor suppressor Tsc2 gene using a
conditional expression system in Tsc2 mutant (Eker) rat renal carcinoma cells.
AB - Alteration of the rat homologue of the tuberous sclerosis 2 (TSC2) gene is
associated with dominantly inherited cancer in the Eker rat model, indicating a
tumor suppressor nature. The ability of Tsc2 to activate signal transduction and
transcription suggests that genes induced by Tsc2 may mediate its biological
roles. Using a subtractive hybridization approach in combination with
tetracycline operator systems, we identified a set of downstream genes affected
by Tsc2. Regulated expression of wild-type Tsc2 gene in Eker renal carcinomas
(RCs) resulted in marked expression of cell arrest or programmed cell-death
related genes and stress-induced genes. Thus, the data suggest that Tsc2 might
contribute to regulation of the cell cycle and cell survival.
PMID- 9647763
TI - The covalent structure of the blue copper-containing nitrite reductase from
Achromobacter xylosoxidans.
AB - The complete amino acid sequence of the blue copper-containing nitrite reductase
enzyme (NiR) from Achromobacter xylosoxidans has been determined by chemical
analysis, supported by high precision mass analysis. The polypeptide chain
contains 336 residues with an overall charge of 0, including the +2 state of each
of the copper ions. The two NiR enzymes for which the three-dimensional
structures have been solved are green in color and have different absorption
spectra than those of the blue-colored protein from A. xylosoxidans. The ligands
to the two copper atoms are conserved. Therefore, the difference between the blue
and the green NiR must depend on subtle changes in the geometry of the type I
copper-sulfur bond. Both overall protein charge and active site charge are
different in A. xylosoxidans NiR which may reflect the use of azurin as electron
donor as opposed to the other enzymes that use pseudoazurin.
PMID- 9647764
TI - Cloning of the histidine biosynthetic genes of Corynebacterium glutamicum:
organization and sequencing analysis of the hisA, impA, and hisF gene cluster.
AB - The hisA and hisF genes of Corynebacterium glutamicum were cloned by transforming
histidine auxotrophic Escherichia coli with the genomic DNA library. They are two
of the eight genes that participate in the histidine biosynthetic pathway. Cloned
DNA fragments containing the genes can also complement hisH and hisI auxotrophs
of Escherichia coli, suggesting that the four genes are clustered in the genome.
We determined the nucleotide sequences of the minimal fragment containing the
hisA and hisF genes, which are separated by the impA gene. The coding regions of
the hisA and hisF genes are 245 and 257 amino acids in length with a predicted
size of about 26 and 27 kDa, respectively. These are in good agreement with the
sizes of proteins expressed in E. coli. A high similarity was observed in
comparison of nucleotide sequences of each protein between C. glutamicum and
other species, as well as those between hisA and hisF genes of C. glutamicum.
PMID- 9647765
TI - Molecular and crystal properties of Bos d 2, an allergenic protein of the
lipocalin family.
AB - The relationship between the molecular structure of allergenic proteins and the
allergenic determinants is one of the central issues in allergology. We report
here that the natural preparation of Bos d 2, a mammalian lipocalin allergen,
comprises three molecular variant proteins of 17,829, 17,781, and 17,800 Da. When
cDNA of Bos d 2 (Genome Sequence Data Base No. L42867) was recloned and expressed
in Pichia pastoris, two proteins were produced. One of the proteins (17,831 Da)
and the proteins in the natural preparation had pyroglutamate as the N-terminal
residue; in the other (17,849 Da) the N-terminal residue was glutamine.
Recombinant Bos d 2 protein was crystallized and the native data set was
collected at 1.8 A resolution.
PMID- 9647766
TI - cDNA sequence and chromosomal localization of the remaining three human nuclear
encoded iron sulphur protein (IP) subunits of complex I: the human IP fraction is
completed.
AB - NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain
can be fragmented in a flavoprotein (FP), iron-sulfur protein (IP), and
hydrophobic protein (HP) subfraction. The IP subfraction is hypothesized to be
significant, since it contains important prosthetic groups highly conserved among
species. We cloned the cDNA of three remaining human NADH:ubiquinone
oxidoreductase subunits of this IP fraction: the NDUFS2 (49 kDa), NDUFS3 (30
kDa), and NDUFS6 (13 kDa) subunits. All presented cDNAs include the complete open
reading frame (ORF), which consist of 1392, 795, and 375 base pairs, coding for
463, 264, and 124 amino acids, respectively. The latter show 96, 90, and 83%
homology with the corresponding bovine translation products. The 3' untranslated
regions (UTR) are complete in all three cDNAs. Polymerase chain reaction
performed with DNA isolated from somatic human-rodent cell hybrids containing
defined human chromosomes as template gave a human-specific signal which mapped
the NDUFS2 and NDUFS3 subunits to chromosomes 1 and 11, respectively. In the case
of the NDUFS6 subunit a pseudogene may be present since signals were seen in the
lanes containing chromosomes 5 and 6. The NDUFS2 contains a highly conserved
protein kinase C phosphorylation site and the NDUFS3 subunit contains a highly
conserved casein kinase II phosphorylation site which make them strong candidates
for future mutation detection studies in enzymatic complex I-deficient patients.
PMID- 9647767
TI - Trimidox-mediated morphological changes during erythroid differentiation is
associated with the stimulation of hemoglobin and F-cell production in human K562
cells.
AB - Trimidox (3,4,5-trihdroxybenzamidoxime) has been shown to reduce the activity of
ribonucleotide reductase with accompanied growth inhibition and differentiation
of mammalian cells. Hydroxyurea (HU) is the only ribonucleotide reductase
inhibitor in clinical use for the treatment and management of sickle cell anemia,
since this compound increases fetal hemoglobin (Hb F) production: a potent
inhibitor of sickle hemoglobin (Hb SS) polymerization. However, the main
limitations of HU is its lack of potency, myelosuppression and short half life.
These studies investigated the effects of trimidox on the induction of hemoglobin
and F-cells production in K562 erythroleukemia cells. Our study reveals that
trimidox exhibits concentration dependent inhibitory effect on K562 cells with
increase in benzidine positive normoblasts and F-cells production as well as
morphological changes typical of erythroid differentiation. These findings
provide the first evidence that the growth inhibitory differentiation of cells
induced by trimidox enhance hemoglobin and F-cells production.
PMID- 9647768
TI - Extra-chromosomal telomere repeat DNA in telomerase-negative immortalized cell
lines.
AB - We found novel extra-chromosomal telomere repeat (ECTR) DNAs in telomerase
negative immortalized KMST-6 cells, by staining these cells with a (TTAGGG)n
probe using both cycling oligonucleotide-primed in situ synthesis and by
fluorescence in situ hybridization. Relatively small amounts of ECTR DNAs were
also observed in telomerase-negative VA13 and SUSM-1 cells, but not observed in
telomerase-positive immortalized HeLa cells. The ECTR DNAs existed mainly in the
nucleoplasm with a small amount in the cytoplasm. The nucleoplasm ECTR DNAs were
co-stained with an antibody directed to the telomeric-repeat binding factor 1
(TRF1), suggesting that they exist as a complex with TRF1. In consistent with
these cytological studies, Southern blot analysis showed the existence of small
telomere repeat DNAs. The ECTR DNA may provide an insight into the elucidation of
the mechanisms responsible for the maintenance of telomeres in telomerase
negative immortalized cells.
PMID- 9647769
TI - Different modes of cell death induced by 5-fluoro-2'-deoxyuridine in two clones
of the mouse mammary tumor FM3A cell line.
AB - The mode of cell death induced by 1 microM 5-fluoro-2'-deoxyuridine (FdUrd)
changed in a wild-type F28-7 clone of mouse mammary tumor FM3A cells after a six
month culture. In the original stocked F28-7 clone, FdUrd-induced cell death was
accompanied by necrosis-like cell swelling and DNA fragmentation to 100-200 kbp.
In subclone F28-7-A isolated from F28-7 cells, which had been cultured for six
months, apoptotic bodies and nucleosomal DNA-ladder fragments were observed with
the treatment. Furthermore, we investigated the differences in FdUrd-induced
intracellular signals between these clones. In F28-7 cells, FdUrd induced
increases in caspase-3-like activity, and the mRNA levels of the c-jun, c-fos and
c-myc genes, which were greater and earlier than those in F28-7-A cells.
Moreover, intracellular acidification occurred in F28-7-A cells treated with
FdUrd, though it was not observed in F28-7 cells. These findings suggest that
FdUrd-induced cell death occurred through the death program to cell lysis
(necrosis) without apoptosis when the induction of these intracellular signals
was very high and when intracellular acidification was deficient. Investigation
of the differences in the mode of FdUrd-induced cell death between these clones
would be important for elucidating the molecular mechanism of pivotal events
guiding cells toward either apoptosis or necrosis.
PMID- 9647770
TI - Detection of activated Caspase-3 by a cleavage site-directed antiserum during
naturally occurring DRG neurons apoptosis.
AB - We prepared a cleavage site-directed antiserum against Caspase-3 (anti-p20/17),
which reacts with the p20/17 fragment (p20/17) activated by cleavage but not
proCaspase-3 (p32), and examined the relationship between the activation of
Caspase-3 and apoptosis. We identified p20/17-positive cells where cell death
occurs naturally: interdigits of the forelimbs, small intestine epithelium,
thymus, trigeminal ganglia, and dorsal root ganglia of mouse embryos. Withdrawal
of nerve growth factor induced the appearance of p20/17-positive cells with DNA
fragmentation in the culture of dorsal root ganglia neurons, while DNA
fragmentation was detected in both p20/17-positive and -negative neurons in
dorsal root ganglia of mouse embryos. These results suggest that not only
activation of Caspase-3 but also other molecular mechanism play a role in the
naturally occurring dorsal root ganglia apoptosis. Cleavage site-directed
antisera against Caspases will be useful for the analysis of the molecular
mechanism of naturally occurring apoptosis during development.
PMID- 9647771
TI - Rapid determination of gap junction formation using HeLa cells microinjected with
cDNAs encoding wild-type and chimeric connexins.
AB - A procedure for rapidly determining the functionality of gap junctions
constructed of recombinant connexins in communication-deficient HeLa cells is
described. Nuclear microinjection of cDNA encoding wild-type connexins (Cx) 26,
32, 43, and a range of connexin-aequorin (Cx-Aeq) chimerase resulted in
generation of gap junction intercellular communication channels. Expression of
recombinant protein was detected in > 95% of cells 18-72 h following nuclear
microinjection, and the functionality of the channels generated was determined
according to their ability to transfer the fluorescent dye tracers Lucifer yellow
and propidium iodide. The dye transfer results obtained correlated closely with
other published studies using stably transfected cells and yet are obtained as
rapidly as 18 h following microinjection of cDNA. Expression of a truncated form
of Cx43 (Cx43 delta 244) by this new method indicated diminished intercellular
transfer of both dyes and supports a channel-gating mechanism that postulates
interaction between the carboxyl tail and the intracellular loop.
PMID- 9647772
TI - Foam cell conversion of macrophages alters the biosynthesis of heparan sulfate.
AB - Heparan sulfate is thought to regulate the biological activities of several
proteins implicated in the pathogenesis of atherosclerosis. While the
interactions of heparan sulfate with lipoprotein lipase and various growth
factors have been actively studied, little is known of the cellular regulation of
heparan sulfate biosynthesis in response to lipid accumulation. We have
investigated heparan sulfate biosynthesis during conversion of murine J774
macrophages into lipid-laden foam cells. Such conversion is shown to accelerate
the rate of glycosaminoglycan synthesis and the transport of newly synthesized
proteoglycans into the medium. Moreover, the structure of heparan sulfate is
specifically altered due to an approximately 30% increase in the 6-O-sulfation of
glucosamine residues within the N-sulfated heparan sulfate domains, whereas the
sulfation of chondroitin sulfate remains unaffected. These results suggest a
selective effect of foam cell conversion on the biosynthesis of heparan sulfate.
PMID- 9647773
TI - Induction of Apg-1, a member of the heat shock protein 110 family, following
transient forebrain ischemia in the rat brain.
AB - Apg-1 (Osp94) and apg-2 belong to the heat shock protein (hsp) 110 family. In
mouse somatic cells the apg-1 and hsp105/110 transcripts are inducible by a 32
degrees C to 39 degrees C heat shock, while apg-2 is not heat-inducible. Since
ischemia is known to induce expression of hsp70, its effect on expression of apg
1 was assessed by using the 20-min forebrain ischemia model of the rat. In the
cerebral cortex, Northern blot analysis and in situ hybridization histochemistry
demonstrated an increased expression in neuronal cells of apg-1 transcripts 3 h
after the onset of reperfusion, with a peak at 12 h, followed by a decline. In
the hippocampus, the level was increased at 3 h, remained constant until 24 h,
and then declined. Transcript levels of apg-2 as well as hsp 105 were also
increased under the present conditions, indicating that the expression of apg-2
was differentially regulated in response to heat and ischemic stresses. The
induction kinetics of hsp 105, but neither apg-2 nor hsp 70, were identical to
those of apg-1. These results demonstrated that brain ischemia/reperfusion
induced expression of each member of the hsp 110 family, although the regulatory
mechanisms may not be the same. They also suggest a significant role of apg-1 in
both the ischemic- and heat-stress responses and in the normal functioning of the
non-stressed neuronal cells.
PMID- 9647774
TI - Interferon-gamma-induced differentiation and apoptosis of HT29 cells:
dissociation of (glucosyl)ceramide signaling.
AB - Recently, (glyco)sphingolipids (SL) like ceramide (Cer) and glucosylceramide
(GlcCer) have been shown to be involved in signaling pathways leading to
differentiation and apoptosis in several cell types, including the colon
adenocarcinoma cell line HT29. Intracellular levels of Cer can be modulated by
ligands such as interferon-gamma (IFN gamma). In the present study we show that
IFN gamma, depending on its concentration, has both differentiation- and
apoptosis-inducing effects on HT29 cells. Since both phenomena have been related
to SL-mediated signaling in other cell types, we next examined whether IFN gamma
was able to induce changes in the SL levels of HT29 cells. Remarkably, no
significant changes in these levels could be revealed, implying that SL are not
involved in IFN gamma-induced differentiation and/or apoptosis of HT29 cells.
This observation provides evidence for the hypothesis that SL-mediated signaling
pathways might be more cell type specific than is generally assumed.
PMID- 9647775
TI - Nitric oxide inhibits c-Jun N-terminal kinase 2 (JNK2) via S-nitrosylation.
AB - S-nitrosylation by S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor,
suppresses the phosphotransferase activity of cJun N-terminal kinase 2
(JNK2)/stress activated protein kinase (SAPK) in dose- and time-dependent manners
in vitro. JNK2 activity is significantly decreased at 10 microM of GSNO, which is
dramatically reversed by adding 10 mM of DTT. Reduced form of glutathione
protects the GSNO-induced suppression of JNK2 activation in a dose-dependent
fashion. However, GSNO-treated Sek1 does not affect the JNK2 activity of
phosphotransferation toward c-Jun N-terminal1-79 protein. These results indicate
that NO may exert a regulatory role of JNK2 activity by S-nitrosylation of the
protein in apoptotic signaling pathway. Suppression of JNK2 phosphotransferase
activity by NO is also supported by the observation that NO plays an important
anti-apoptotic roles in heptocytes, splenocytes, eosinophils and B lymphocytes.
PMID- 9647776
TI - Isolation and characterization of the mouse beta 2/neuroD gene promoter.
AB - Beta2/neuroD is a basic helix-loop-helix protein involved in differentiation of
the endocrine pancreas and the central nervous system. A 2-kb fragment containing
the 5' upstream region of the mouse beta2/neuroD gene was cloned and sequenced.
The cloned fragment was tested for promoter activity in six cell lines. Strong
promoter activity was apparent in the three pancreatic beta cell lines, beta-HC3,
beta-HC9, and NIT-1, whereas weak activity was seen in NIH 3T3, Rat-1, and MCF-7
cell lines. Analysis of promoter activity of deletion mutants in beta-HC3 cells
indicated that while basal promoter activity was observed with a fragment which
extended -109 bp upstream of the transcription start site, maximal activity
required the fragment -2091 to -297 bp.
PMID- 9647777
TI - Stimulation of primed neutrophils by soluble immune complexes: priming leads to
enhanced intracellular Ca2+ elevations, activation of phospholipase D, and
activation of the NADPH oxidase.
AB - Soluble immune complexes activate a rapid burst of reactive oxidant secretion
from neutrophils that have previously been primed with GM-CSF. Binding of these
complexes to the cell surface of unprimed neutrophils results in the generation
of intracellular Ca2+ transients, but the NADPH oxidase fails to become
activated. No phospholipase D activity was observed following the addition of
soluble immune complexes to unprimed cells. Upon priming with GM-CSF, the
intracellular Ca2+ signal generated following soluble complex binding was greatly
extended and phospholipase D was activated: there was also increased
phosphorylation of proteins on tyrosine residues and the NADPH oxidase was
activated. When Ca2+ influx was prevented, this phospholipase D activity was not
observed. This primed oxidase activity was completely inhibited by erbstatin.
Treatment of unprimed neutrophils with pervanadate (to inhibit protein tyrosine
phosphatases) mimicked the effects of priming in that pervanadate-treated
neutrophils secreted reactive oxidants in response to soluble immune complexes.
The data indicate that during priming a new signaling pathway is activated that
involves Ca2+ influx, phosphorylation on tyrosine residues, phospholipase D
activity, and NADPH oxidase activation.
PMID- 9647778
TI - Alpha 4 associates with protein phosphatases 2A, 4, and 6.
AB - Protein phosphatases participate in the regulation of a variety of cellular
processes. Control of their enzymatic activity and specificity is made possible
largely by an array of regulatory subunits. Novel serine/threonine phosphatases-
PP4 and PP6 in human cells--have been discovered recently, for which regulatory
subunits are yet to be identified. We report here the identification of a
potential regulatory subunit of these phosphatases. Using the yeast two-hybrid
system, we have found that alpha 4, a previously identified phosphoprotein,
associates constitutively with the catalytic subunits of PP4, PP6, and both
isoforms of PP2A. These interactions have been confirmed by direct binding and do
not require phosphorylation of alpha 4, although it is unclear whether alpha 4
phosphorylation has any effect on its association with the phosphatases. The
binding activity appears to reside in the N-terminal 50 amino acids of the
phosphatases, consistent with a previous observation that the first 55 residues
of PPV, a Drosophila homolog of PP6, may harbor the element for regulation. alpha
4 shares 37% sequence homology with Tap42, an S. cerevisiae protein that has been
reported to associate with PP2A and Sit4 (yeast homolog of PP6) and comprises a
regulatory component in the rapamycin-sensitive Tor signalling pathway. By
analogy, alpha 4 and its associated phosphatases may participate in the mammalian
rapamycin-sensitive pathway mediated by FRAP.
PMID- 9647779
TI - Differential expression of human histone deacetylase mRNAs in response to immune
cell apoptosis induction by trichostatin A and butyrate.
AB - The reversible acetylation of histones by histone deacetylases (HDACs) and
acetyltransferases (HATs) plays a fundamental role in gene transcription. We
previously showed that HDAC mRNA is upregulated in immune cells upon PHA-induced
activation. Little is known, however, about the differential regulation of HDAC
mRNAs by the HDAC inhibitors Trichostatin A (TSA) and butyrate, agents known to
block proliferation and induce apoptosis. We report that apoptosis-inducing
concentrations of TSA and butyrate upregulate the expression of HDAC mRNAs in a
differential manner and act synergistically with PHA to induce HDAC expression,
suggesting the presence of independent HDAC regulatory mechanisms. Moreover, we
show that HDAC inhibitor-induced apoptosis is associated with early abrogation of
gamma-IFN production by Th1 lymphocytes and with p53 mRNA downregulation. Our
findings highlight the dynamic interplay of cell cycle-, activation- and
apoptosis-related proteins in association with time-dependent expression of HDACs
and are suggestive of different specific roles for these enzymes.
PMID- 9647780
TI - Potent inhibition of CTLA-4 expression by an anti-CTLA-4 ribozyme.
AB - Blockading the negative-regulatory CTLA-4 receptor has emerged as a powerful
strategy with clinical potential to enhance T-cell responses. Some experimental
tumors, for example, are rejected when anti-CTLA-4 antibodies are administered in
vivo. The concise target cells and downstream events, however, remain to be
defined. The development of gene transfer reagents that inhibit CTLA-4 may
facilitate such investigations and may expand the therapeutic range. This
communication describes an anti-CTLA-4 hairpin ribozyme that specifically
abrogates CTLA-4 expression after gene transfer into a murine T-cell model. The
analysis of multiple and independently derived clones and bulk cultures showed
that CTLA-4 induction was inhibited > 90% at the RNA level and that it was
undetectable at the protein level, with and without selective pressure. This
potent inhibition required the catalytic function of the ribozyme. The anti-CTLA
4 ribozyme may be an alternative tool with which to continue the functional and
therapeutical exploration of CTLA-4.
PMID- 9647781
TI - Run-down of L-type Ca2+ channels occurs on the alpha 1 subunit.
AB - Run-down of L-type Ca2+ channels in CHO cells stably expressing alpha 1c, alpha
1c beta 1a, or alpha 1c beta 1a alpha 2 delta gamma subunits was studied using
the patch-clamp technique (single channel recording). The channel activity (NPo)
of alpha 1c channels was increased 4- and 8-fold by coexpression with beta 1a and
beta 1a alpha 2 delta gamma, respectively. When membranes containing channels
composed of different subunits were excised into basic internal solution, the
channel activity exhibited run-down, the time-course of which was independent of
the subunit composition. The run-down was restored by the application of
calpastatin (or calpastatin contained in cytoplasmic P-fraction) + H-fraction (a
high molecular mass fraction of bovine cardiac cytoplasm) + 3 mM ATP, which has
been shown to reverse the run-down in native Ca2+ channels in the guinea-pig
heart. The restoration level was 64.7, 63.5, and 66.4% for channels composed of
alpha 1c, alpha 1c beta 1a, and alpha 1c beta 1a alpha 2 delta gamma,
respectively, and was thus also independent of the subunit composition. We
conclude that run-down of L-type Ca2+ channels occurs via the alpha 1 subunit and
that the cytoplasmic factors maintaining Ca2+ channel activity act on the alpha 1
subunit.
PMID- 9647782
TI - WNT-1 and HGF regulate GSK3 beta activity and beta-catenin signaling in mammary
epithelial cells.
AB - Wnt-1, a secreted glycoprotein, participates in development of the nervous system
and contributes to mammary oncogenesis when overexpressed. We show that GSK3
activity is decreased in mouse mammary cells transformed by Wnt-1. These cells
also exhibit a substantial Wnt-1 dependent increase in the uncomplexed population
of beta-catenin. Wnt-1 signaling does not change the steady state level of either
GSK3 alpha or GSK3 beta but instead leads to an increased association between
GSK3 beta and beta-catenin. HGF/SF treatment of mouse mammary cells also leads to
a transient decrease in GSK3 activity and a parallel, selective increase in the
uncomplexed pool of beta-catenin. Both Wnt-1 and HGF/SF lead to nuclear
accumulation of beta-catenin and activation of a LEF/Tcf responsive reporter
gene. This study defines a pivotal signal transduction pathway, activated by both
Wnt-1 and HGF/SF, leading to decreased GSK3 beta activity and consequently an
increase in the free pool and nuclear accumulation of beta-catenin and changes in
gene expression.
PMID- 9647783
TI - Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs,
competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump.
AB - Overexpression of the multidrug resistance-associated protein (MRP1) gene
encoding a human GS-X pump in cultured cells resulted in increased cellular
resistance to antitumor agents, including doxorubicin (Dox) and daunomycin (Dau),
as well as certain heavy metals. However, studies with membrane vesicles prepared
from the resistant cells revealed that Dox and Dau are poor substrates for the
transport mediated by MRP/GS-X pump, suggesting that metabolic modifications of
these drugs might be required for the transport. To test this hypothesis, we
prepared four glutathione conjugates by linking the cysteine residue of GSH to
Dox and Dau at eitehr the C-7 or C-14 position. The affinity of the synthesized
conjugates toward MRP/GS-X pump was examined in the LTC4 transport assay using
membrane vesicles prepared from an MRP1 gene-overexpressing cell line, SR3A.
Unconjugated Dox and Dau failed to inhibit the transport of LTC4, whereas 30
microM GS-Dox or GS-Dau conjugates completely inhibited the transport. Kinetic
analyses revealed that the inhibition by these GS-conjugates is competitive with
Ki values ranging from 60 to 200 nM, suggesting that these compounds have high
affinities toward MRP/GS-X pump and share the common binding site(s) with LTC4.
Our present results support the hypothesis that glutathionation can facilitate
the transport of anthracyclines by the MRP/GS-X pump.
PMID- 9647784
TI - Cloning of cDNAs encoding porcine and human DNase II.
AB - We report the molecular cloning of cDNAs encoding porcine and human DNase II and
the genomic structure of the human DNase II gene. The full length cDNAs for
porcine and human DNase II were isolated by polymerase chain reaction on the
basis of amino acid sequences determined for the tryptic peptides of porcine
liver DNase II. The porcine and human cDNAs contain 1095 and 1083 bp open reading
frames, respectively, and encode 364 and 360 amino acid proteins with calculated
molecular masses of 40,157 and 39,555, respectively. The amino acid sequencing of
purified porcine DNase II reveals two N-termini with corresponding sequences
present within the same open reading frame, suggesting proteolytic processing for
the covalently bonded subunit structure of DNase II. Northern blot analysis
demonstrated that a single transcript of 2.0 kb mRNA coding for DNase II is
ubiquitously expressed in human tissues. A database search revealed that the
human genomic sequence of chromosome 19p13.2 contains the DNase II gene.
Characterization of the genomic sequence showed that the DNase II gene consists
of six exons separated by five introns whose splice acceptor/donor sites agree
with the GT/AG rule.
PMID- 9647786
TI - Structural conservation in RNA loops III and VI of the internal ribosome entry
sites of enteroviruses and rhinoviruses.
AB - Alignment of the internal ribosome entry sites (IRES) of members of the
Enteroviridae-Rhinoviridae (E/R) family reveals a consensus loop sequence of
AANCCA closed by a C.G base pair. The consensus sequence was present in two
distinct loops in domains III and VI. Four hairpins corresponding to the most
common loop sequences, AAUCCA, AAACCA, GAACCA and AUCCA, were synthesized and
studied by UV spectroscopy. Although all four oligomers had similar UV melting
points their thermodynamic parameters revealed differing stabilities consistent
with their loop size. Comparison of the aromatic proton and H1' chemical shifts
for the four loop sequences obtained from this and our previous NMR study
revealed strikingly similar trends. The pattern of chemical shifts suggest
similar solution structures in spite of differences in sequence and loop size.
This common structure provides a structural basis for their sequence conservation
in E/R IRESes.
PMID- 9647785
TI - Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of
polymorphonuclear leukocytes.
AB - Dermaseptin (DRs S1), a 34-amino acid residue cationic antimicrobial peptide was
studied for its effects on the production of reactive oxygen species (respiratory
burst) and exocytosis of polymorphonuclear leukocytes (PMN). Treatment of PMN
with DRs S1 (10-100 nM) stimulated significant production of reactive oxygen
species (approximately a 2-fold increase relative to control) and release of
myeloperoxidase. In addition, low DRs S1 concentrations (1-10 nM) primed the
stimulation of respiratory burst induced by zymosan particles. In contrast to the
native peptide, a dermaseptin fragment without either the COOH-terminal (DRs 1
10) or NH2 terminal (DRs 16-34) portion was inactive. The DRs S1-induced
respiratory burst was inhibited by a selective protein kinase C inhibitor, GF
109203X, and was associated with early signalling events such as a rapid and
transient elevation of cytosolic-free calcium concentration and phospholipase D
activity. These data provide the first evidence of stimulating and priming
properties of a peptide antibiotic on microbicidal activities of neutrophils,
suggesting a potential role of dermaseptin in modulating host-defense mechanisms.
PMID- 9647787
TI - High-affinity binding sites to the vitamin D receptor DNA binding domain in the
human growth hormone promoter.
AB - The regulation of the human growth hormone (hGH) gene by 1,25(OH)2D3 is a
mechanism which is poorly understood. The objective of this study was to
investigate whether the hGH gene has DNA recognition elements for the DNA binding
domain of the vitamin D receptor. Using gel retardation assays and footprinting
techniques, two high-affinity binding sites, denominated F1 and F2, were
identified in the 5'-flanking sequence of hGH. The distal site, F1, located at
59 bp is made up of an imperfect direct repeat separated by 3 bp and showed a
high degree of similarity with other known vitamin D response elements (VDREs).
The proximal site, F2, located at -36 bp showed a single 7-bp sequence, which is
different from other known VDREs. The location of both sites (F1 near the GHF
1/Pit-1 response element, F2 contacting the TATA box) suggests that the vitamin D
receptor by itself or through interference with other transcriptional factors may
modulate hGH expression.
PMID- 9647788
TI - Localization of RhoA GTPase to endothelial caveolae-enriched membrane domains.
AB - Caveolae are small microdomains of the plasma membrane that are thought to play
important roles in signal transduction processes. In this work, we have
investigated the association of Rho proteins with caveolae-enriched membrane
domains isolated from cultured endothelial cells. Fractionation of ECV304 cells
by sucrose gradient density centrifugation in the absence of detergent resulted
in the co-sedimentation of a significant proportion of RhoA and Cdc42 with known
caveolae marker proteins, including caveolin, but not with other non-caveolae
membrane proteins such as the angiotensin-converting enzyme. Immunoprecipitation
experiments carried on crude endothelial cell lysates as well as with solubilized
caveolae-enriched membrane domains showed the coimmunoprecipitation of caveolin
with RhoA but not with Cdc42. Incubation of endothelial cell lysates with a
glutathione-S-transferase (GST)-RhoA fusion protein resulted in the specific
precipitation of caveolin, while addition of GST-caveolin-1 to the lysates
promoted the precipitation of RhoA. Moreover, incubation of bacterially expressed
RhoA with GST-caveolin-1 resulted in the precipitation of RhoA, indicating that
RhoA directly interacts with caveolin-1. This interaction was found to be
nucleotide-independent and was not affected by prior modification of RhoA with
the C3 exoenzyme from C. botulinium or with the cytotoxic necrotinizing factor
from E. coli. Taken together, these results suggest the association of RhoA with
endothelial caveolae-enriched membrane domains, likely through physical
interaction with caveolin-1. These findings may provide new insights into the
functions played by Rho proteins and caveolae in signal transduction events.
PMID- 9647789
TI - Highly specific and quantitative activation of STATs in 3T3-L1 adipocytes.
AB - We have recently demonstrated that STATs 1, 3, 5A, 5B, and 6 are expressed in
adipocytes. Using the 3T3-L1 cell line, we have examined the activation of all
adipocyte expressed STATs by 23 different factors which are either potent
regulators of adipocyte gene expression or known STAT activators in other cell
types. STAT activation was assessed by examining nuclear translocation and
tyrosine phosphorylation in serum deprived, fully differentiated 3T3-L1
adipocytes. Unlike other adipocyte-expressed STATs, STAT 5A was present in the
nucleus under basal conditions. Of all the activators examined, only growth
hormone was capable of causing STATs 5A and 5B to translocate to the nucleus.
None of the activators were capable of affecting the cellular distribution of
STAT 6. Furthermore, our results indicate that there is a quantitative activation
of STATs 1 and 3 by LIF, OSM, and IFN-gamma as measured by both nuclear
translocation and tyrosine phosphorylation in whole cell extracts. IFN-gamma is a
potent activator of STAT 1 and a weaker activator of STAT 3, whereas LIF and OSM
are potent activators of STAT 3 and weaker activators of STAT 1. These studies
demonstrate that STAT activation in adipocytes is highly specific, quantitative,
and distinct.
PMID- 9647790
TI - Ancient DNA in human bone remains from Pompeii archaeological site.
AB - aDNA extraction and amplification procedures have been optimized for Pompeian
human bone remains whose diagenesis has been determined by histological analysis.
Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid
repeat sequences) have been performed and compared with anthropometric data on
sexing.
PMID- 9647791
TI - Demonstration of receptors specific for connective tissue growth factor on a
human chondrocytic cell line (HCS-2/8).
AB - The presence of receptors specific for connective tissue growth factor (CTGF) was
demonstrated on a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8.
The binding of 125I-labeled recombinant CTGF to HCS-2/8 cells was inhibited by
unlabeled CTGF but not by PDGF-BB or bFGF. Scatchard analysis revealed the
presence of two classes of binding sites with Kd values of 18.6 and 259 nM on
cells. A cross-linking study revealed the formation of 125I-CTGF-receptor complex
with an apparent molecular weight of 280 kDa. The 125I-CTGF-receptor complex
disappeared almost completely on the addition of unlabeled CTGF but not PDGF-BB
or bFGF. In addition, the 125I-CTGF-receptor complex was immunoprecipitated with
anti-CTGF antiserum but not with anti-PDGF receptor antiserum. These findings
suggest that CTGF directly binds to specific receptor molecules on HCS-2/8 cells.
PMID- 9647795
TI - Structure-activity study of the lantibiotic mutacin II from Streptococcus mutans
T8 by a gene replacement strategy.
AB - Mutacin II, elaborated by group II Streptococcus mutans, is a ribosomally
synthesized and posttranslationally modified polypeptide antibiotic containing
unusual thioether and didehydro amino acids. To ascertain the role of specific
amino acid residues in mutacin II antimicrobial activity, we developed a
streptococcal expression system that facilitates the replacement of the mutA gene
with a single copy of a mutated variant gene. As a result, variants of mutacin II
can be designed and expressed. The system was tested by constructing the
following mutant peptides: delta N1, V7A, P9A, T10A, T10S, C15A, C26A, and C27A.
All of these mutacin II variants except delta N1 and T10A, which were not
secreted, were isolated, and their identities were verified by mass spectrometry.
Variants P9A, C15A, C26A, and C27A failed to exert antimicrobial activity.
Because the P9A and T10A variants comprise the "hinge" region of mutacin II,
these observations suggest that in addition to the thioether and didehydro amino
acids, the hinge region is essential for biological activity and biosynthesis or
export of the peptide. Tandem mass spectrometry of the N-terminal part of the
wild-type molecule and its C15A variant confirmed that the threonine at position
10 is dehydrated and present as a didehydrobutyrine residue. This analysis of the
active T10S variant further suggested that a didehydro amino acid at this
position is specific for antimicrobial activity and that the biosynthetic
machinery does not discriminate between threonine and serine. In contrast, the
lack of production of mutacin variants with alanine substituted for threonine at
position 10, as well as the deletion of asparagine at the N terminus (delta N1),
indicates that specific residues in the propeptide may be crucial for certain
steps in the biosynthetic pathway of this lantibiotic.
PMID- 9647796
TI - Root colonization by Agrobacterium tumefaciens is reduced in cel, attB, attD, and
attR mutants.
AB - Root colonization by Agrobacterium tumefaciens was measured by using tomato and
Arabidopsis thaliana roots dipped in a bacterial suspension and planted in soil.
Wild-type bacteria showed extensive growth on tomato roots; the number of
bacteria increased from 10(3) bacteria/cm of root length at the time of
inoculation to more than 10(7) bacteria/cm after 10 days. The numbers of
cellulose-minus and nonattaching attB, attD, and attR mutant bacteria were less
than 1/10,000th the number of wild-type bacteria recovered from tomato roots. On
roots of A. thaliana ecotype Landsberg erecta, the numbers of wild-type bacteria
increased from about 30 to 8,000 bacteria/cm of root length after 8 days. The
numbers of cellulose-minus and nonattaching mutant bacteria were 1/100th to
1/10th the number of wild-type bacteria recovered after 8 days. The attachment of
A. tumefaciens to cut A. thaliana roots incubated in 0.4% sucrose and observed
with a light microscope was also reduced with cel and att mutants. These results
suggest that cellulose synthesis and attachment genes play a role in the ability
of the bacteria to colonize roots, as well as in bacterial pathogenesis.
PMID- 9647797
TI - Epidemiological typing of Campylobacter isolates from meat processing plants by
pulsed-field gel electrophoresis, fatty acid profile typing, serotyping, and
biotyping.
AB - Campylobacter spp. are a leading cause of bacterial gastroenteritis. Foods of
animal origin, particularly under-cooked poultry, are common sources of
Campylobacter species associated with disease in humans. A collection of 110
Campylobacter jejuni and 31 C. coli human and environmental isolates from
different Ontario, Canada, abattoirs were analyzed by pulsed-field gel
electrophoresis, fatty acid profile typing, and biotyping. Previously collected
serotyping data for the same isolates were also analyzed in this study. Pulsed
field gel electrophoresis was found to be the most discriminatory of the typing
methods, followed by serotyping, fatty acid profile typing, and biotyping. A wide
variety of typing profiles were observed within the isolates, suggesting that
several different Campylobacter sp. strains were present within the abattoirs.
PMID- 9647798
TI - Degradation and Fate of Carbon Tetrachloride in Unadapted Methanogenic Granular
Sludge.
AB - The potential of granular sludge from upflow anaerobic sludge blanket (UASB)
reactors for bioremediation of chlorinated pollutants was evaluated by using
carbon tetrachloride (CT) as a model compound. Granular sludges cultivated in
UASB reactors on methanol, a volatile fatty acid mixture, or sucrose readily
degraded CT supplied at a concentration of 1,500 nmol/batch (approximately 10 uM)
without any prior exposure to organohalogens. The maximum degradation rate was
1.9 umol of CT g of volatile suspended solids-1 day-1. The main end products of
CT degradation were CO2 and Cl-, and the yields of these end products were 44 and
68%, respectively, of the initial amounts of [14C]CT and CT-Cl. Lower chlorinated
methanes accumulated in minor amounts temporarily. Autoclaved (dead) sludges were
capable of degrading CT at rates two- to threefold lower than those for living
sludges, indicating that abiotic processes (mediated by cofactors or other sludge
components) played an important role in the degradation observed. Reduced
components in the autoclaved sludge were vital for CT degradation. A major part
(51%) of the CT was converted abiotically to CS2. The amount of CO2 produced
(23%) was lower and the amount of Cl- produced (86%) was slightly higher with
autoclaved sludge than with living sludge. Both living and autoclaved sludges
could degrade chloroform. However, only living sludge degraded dichloromethane
and methylchloride. These results indicate that reductive dehalogenation, which
was mediated better by living sludge than by autoclaved sludge, is only a minor
pathway for CT degradation. The main pathway involves substitutive and oxidative
dechlorination reactions that lead to the formation of CO2. Granular sludge,
therefore, has outstanding potential for gratuitous dechlorination of CT to safe
end products.
PMID- 9647799
TI - Thermotoga neapolitana homotetrameric xylose isomerase is expressed as a
catalytically active and thermostable dimer in Escherichia coli.
AB - The xylA gene from Thermotoga neapolitana 5068 was expressed in Escherichia coli.
Gel filtration chromatography showed that the recombinant enzyme was both a
homodimer and a homotetramer, with the dimer being the more abundant form. The
purified native enzyme, however, has been shown to be exclusively tetrameric. The
two enzyme forms had comparable stabilities when they were thermoinactivated at
95 degrees C. Differential scanning calorimetry revealed thermal transitions at
99 and 109.5 degrees C for both forms, with an additional shoulder at 91 degrees
C for the tetramer. These results suggest that the association of the subunits
into the tetrameric form may have little impact on the stability and biocatalytic
properties of the enzyme.
PMID- 9647800
TI - Growth on urea can trigger death and peroxidation of the cyanobacterium
Synechococcus sp. strain PCC 7002.
AB - Laboratory conditions have been identified that cause the rapid death of cultures
of cyanobacteria producing urease. Once the death phase had initiated in the
stationary growth phase, cells were rapidly bleached of all pigmentation. Null
mutations in the ureC gene, encoding the alpha subunit of urease, were
constructed, and these mutants were no longer sensitive to growth in the presence
of urea. High levels of peroxides, including lipid peroxides, were detected in
the bleaching cells. Exogenously added polyunsaturated fatty acids triggered a
similar death response. Vitamin E suppressed the formation of peroxides and
delayed the onset of cell bleaching. The results suggest that these
cyanobacterial cells undergo a metabolic imbalance that ultimately leads to
oxidative stress and lipid peroxide formation. These observations may provide
insights into the mechanism of sudden cyanobacterial bloom disappearance in
nature.
PMID- 9647801
TI - Isolation and entomotoxic properties of the Xenorhabdus nematophilus F1
lecithinase.
AB - Xenorhabdus spp. and Photorhabdus spp., entomopathogenic bacteria symbiotically
associated with nematodes of the families Steinernematidae and Heterorhabditidae,
respectively, were shown to produce different lipases when they were grown on
suitable nutrient agar. Substrate specificity studies showed that Photorhabdus
spp. exhibited a broad lipase activity, while most of the Xenorhabdus spp.
secreted a specific lecithinase. Xenorhabdus spp. occur spontaneously in two
variants, phase I and phase II. Only the phase I variants of Xenorhabdus
nematophilus and Xenorhabdus bovienii strains produced lecithinase activity when
the bacteria were grown on a solid lecithin medium (0.01% lecithin nutrient agar;
24 h of growth). Five enzymatic isomers responsible for this activity were
separated from the supernatant of a X. nematophilus F1 culture in two
chromatographic steps, cation-exchange chromatography and C18 reverse-phase
chromatography. The substrate specificity of the X. nematophilus F1 lecithinase
suggested that a phospholipase C preferentially active on phosphatidylcholine
could be isolated. The entomotoxic properties of each isomer were tested by
injection into the hemocoels of insect larvae. None of the isomers exhibited
toxicity with the insects tested, Locusta migratoria, Galleria mellonella,
Spodoptera littoralis, and Manduca sexta. The possible role of lecithinase as
either a virulence factor or a symbiotic factor is discussed.
PMID- 9647802
TI - Analysis of molecular size distributions of cellulose molecules during hydrolysis
of cellulose by recombinant Cellulomonas fimi beta-1,4-glucanases.
AB - Four beta-1,4-glucanases (cellulases) of the cellulolytic bacterium Cellulomonas
fimi were purified from Escherichia coli cells transformed with recombinant
plasmids. Previous analyses using soluble substrates had suggested that CenA and
CenC were endoglucanases while CbhA and CbhB resembled the exo-acting
cellobiohydrolases produced by cellulolytic fungi. Analysis of molecular size
distributions during cellulose hydrolysis by the individual enzymes confirmed
these preliminary findings and provided further evidence that endoglucanase CenC
has a more processive hydrolytic activity than CenA. The significant differences
between the size distributions obtained during hydrolysis of bacterial
microcrystalline cellulose and acid-swollen cellulose can be explained in terms
of the accessibility of beta-1,4-glucan chains to enzyme attack. Endoglucanases
and cellobiohydrolases were much more easily distinguished when the acid-swollen
substrate was used.
PMID- 9647803
TI - Molecular cloning, sequencing, and expression of a chemoreceptor gene from
Leptospirillum ferrooxidans.
AB - We have cloned and sequenced a 2,262-bp chromosomal DNA fragment from the
chemolithoautotrophic acidophilic bacterium Leptospirillum ferrooxidans. This DNA
contained an open reading frame for a 577-amino-acid protein showing several
characteristics of the bacterial chemoreceptors and, therefore, we named this
gene lcrI for Leptospirillum chemotaxis receptor I. This is the first sequence
reported for a gene from L. ferrooxidans encoding a protein. The lcrI gene showed
both sigma 28-like and sigma 70-like putative promoters. The LcrI deduced protein
contained two hydrophobic regions most likely corresponding to the two
transmembrane regions present in all of the methyl-accepting chemotaxis proteins
(MCPs) which make them fold with both periplasmic and cytoplasmic domains. We
have proposed a cytoplasmic domain for LcrI, which also contains the highly
conserved domain (HCD region), present in all of the chemotactic receptors, and
two probable methylation sites. The in vitro expression of a DNA plasmid
containing the 2,262-bp fragment showed the synthesis of a 58-kDa protein which
was immunoprecipitated by antibodies against the Tar protein (an MCP from
Escherichia coli), confirming some degree of antigenic conservation. In addition,
this 58-kDa protein was expressed in E. coli, being associated with its
cytoplasmic membrane fraction. It was not possible to determine a chemotactic
receptor function for LcrI expressed in E. coli. This was most likely due to the
fact that the periplasmic pH of E. coli, which differs by 3 to 4 pH units from
that of acidophilic chemolithotrophs, does not allow the right conformation for
the LcrI periplasmic domain.
PMID- 9647804
TI - Detoxification of Benzoxazolinone Allelochemicals from Wheat by Gaeumannomyces
graminis var. tritici, G. graminis var. graminis, G. graminis var. avenae, and
Fusarium culmorum.
AB - The ability of phytopathogenic fungi to overcome the chemical defense barriers of
their host plants is of great importance for fungal pathogenicity. We studied the
role of cyclic hydroxamic acids and their related benzoxazolinones in plant
interactions with pathogenic fungi. We identified species-dependent differences
in the abilities of Gaeumannomyces graminis var. tritici, Gaeumannomyces graminis
var. graminis, Gaeumannomyces graminis var. avenae, and Fusarium culmorum to
detoxify these allelochemicals of gramineous plants. The G. graminis var.
graminis isolate degraded benzoxazolin-2(3H)-one (BOA) and 6-methoxy-benzoxazolin
2(3H)-one (MBOA) more efficiently than did G. graminis var. tritici and G.
graminis var. avenae. F. culmorum degraded BOA but not MBOA. N-(2-Hydroxyphenyl)
malonamic acid and N-(2-hydroxy-4-methoxyphenyl)-malonamic acid were the primary
G. graminis var. graminis and G. graminis var. tritici metabolites of BOA and
MBOA, respectively, as well as of the related cyclic hydroxamic acids. 2-Amino-3H
phenoxazin-3-one was identified as an additional G. graminis var. tritici
metabolite of BOA. No metabolite accumulation was detected for G. graminis var.
avenae and F. culmorum by high-pressure liquid chromatography. The mycelial
growth of the pathogenic fungi was inhibited more by BOA and MBOA than by their
related fungal metabolites. The tolerance of Gaeumannomyces spp. for
benzoxazolinone compounds is correlated with their detoxification ability. The
ability of Gaeumannomyces isolates to cause root rot symptoms in wheat (cultivars
Rektor and Astron) parallels their potential to degrade wheat allelochemicals to
nontoxic compounds.
PMID- 9647805
TI - Flow cytometry detection of infectious rotaviruses in environmental and clinical
samples.
AB - A method for the detection of infectious human rotaviruses based on infection of
CaCo-2 cells and detection of infected cells by indirect immunofluorescence and
flow cytometry (IIF-FC) has been developed. The technique was validated by
performing a seminested reverse transcription-PCR assay with sorted cell
populations. The efficiency of the procedure has been compared with that of the
standard method of infection of MA104 cells and ulterior detection by IIF and
optical microscopy (IIF-OM) and with that of infection of MA104 cells and
detection by IIF-FC. The limit of sensitivity for the detection of the cell
adapted strain Ito(r) P13, expressed as the most probable number of
cytopathogenic units, was established as 200 and 2 for MA104 and CaCo-2 cells,
respectively, by the IIF-FC method. The ratio of infectious virus particles to
total virus particles for a wild-type rotavirus was determined to be 1/2 x 10(6)
and 1/2 x 10(4) for IIF-OM with MA104 cells and IIF-FC with CaCo-2 cells,
respectively. The use of IIF-FC with CaCo-2 cells was tested with fecal and water
samples and proved to be more effective than the standard procedure for rotavirus
detection.
PMID- 9647806
TI - Atmospheric Methane Consumption by Forest Soils and Extracted Bacteria at
Different pH Values.
AB - The effect of pH on atmospheric methane (CH4) consumption was studied with
slurries of forest soils and with bacteria extracted from the same soils. Soil
samples were collected from a mixed hardwood stand in New Hampshire, from
jackpine and aspen stands at the BOREAS (Boreal Ecosystem Atmosphere Study) site
near Thompson, northern Manitoba, from sites in southern Quebec, including a
beech stand and a meadow, and from a site in Ontario (cultivated humisol).
Consumption of atmospheric CH4 (concentration, approximately 1.8 ppm) occurred at
depths of >5 cm in both acidic (pH 4.5 to 5.2) and alkaline (pH 7.2 to 7.8)
soils. In slurries of acidic soils, maximum activity occurred at different pH
values (pH 4.0 to 6.5). Bacteria extracted from these soils by high-speed
blending and density gradient centrifugation showed pH responses different from
the pH responses of the slurries. In all cases, these bacteria had a
methanotrophy pH optimum of 5.8 and exhibited no activity at pH 6.8 to 7.0, the
pH optimum range for known methanotrophs. This difference in pH responses could
be useful in modifying media currently used for isolation of these organisms.
Methanotrophic activity was induced in previously non-CH4-consuming soils by
preincubation with 5% (vol/vol) CH4 (50,000 ul of CH4 per liter) or by liquid
enrichment with 20% CH4. The bacteria showed pH responses typical of known
methanotrophs and not typical of preexisting consumers of ambient CH4.
Furthermore, methanotrophs induced by high CH4 levels were more readily extracted
from soil than preexisting ambient CH4 consumers were. In the alkaline soils,
preexisting activity either was destroyed or resisted extraction by the procedure
used. The results support the hypothesis that consumers of ambient CH4 in soils
are physiologically distinct from the known methanotrophs.
PMID- 9647807
TI - Heterologous protein secretion directed by a repressible acid phosphatase system
of Kluyveromyces lactis: characterization of upstream region-activating sequences
in the KIPHO5 gene.
AB - Transcription of the repressible acid phosphatase gene (KIPHO5) in Kluyveromyces
lactis is strongly regulated in response to the level of inorganic phosphate (Pi)
present in the growth medium. We have begun a study of the promoter region of
this gene in order to identify sequences involved in the phosphate control of
KIPHO5 expression and to design new expression-secretion systems in K. lactis.
Deletion analysis and directed mutagenesis revealed two major identical upstream
activating sequences (UAS) CACGTG at positions -430 (USA1) and -192 (UAS2)
relative to the ATG initiation codon. These sequences are identical to those
described for Saccharomyces cerevisiae for the binding of Pho4p. Deletion or
directed mutagenesis of either one or both UAS reduce KIPHO5 expression by the
same amount (approximately 80%). When fused to the coding region of trout growth
hormone cDNA (tGH-II), the promoter and signal peptide-encoding region of the
phosphate-repressible KIPHO5 gene drives the expression of this gene and the
secretion of the tGHII protein. Synthesis of tGHIIp in K. lactis transformants
carrying this construct was found to be regulated by the Pi present in the
medium; depression of heterologous protein expression can therefore be achieved
by lowering the Pi concentration.
PMID- 9647808
TI - Role of Organic Acids in the Manganese-Independent Biobleaching System of
Bjerkandera sp. Strain BOS55
AB - Bjerkandera sp. strain BOS55 is a white rot fungus that can bleach EDTA-extracted
eucalyptus oxygen-delignified kraft pulp (OKP) without any requirement for
manganese. Under manganese-free conditions, additions of simple physiological
organic acids (e.g., glycolate, glyoxylate, oxalate, and others) at 1 to 5 mM
stimulated brightness gains and pulp delignification two- to threefold compared
to results for control cultures not receiving acids. The role of the organic
acids in improving the manganese-independent biobleaching was shown not to be due
to pH-buffering effects. Instead, the stimulation was attributed to enhanced
production of manganese peroxidase (MnP) and lignin peroxidase (LiP) as well as
increased physiological concentrations of veratryl alcohol and oxalate. These
factors contributed to greatly improved production of superoxide anion radicals,
which may have accounted for the more extensive biobleaching. Optimum
biobleaching corresponded most to the production of MnP. These results suggest
that MnP from Bjerkandera is purposefully produced in the absence of manganese
and can possibly function independently of manganese in OKP delignification. LiP
probably also contributed to OKP delignification when it was present.
PMID- 9647809
TI - Differentiation of Lactobacillus Species by Molecular Typing.
AB - A total of 64 type, reference, clinical, health food, and stock isolates of
microaerophilic Lactobacillus species were examined by restriction fragment
length polymorphisms. Of particular interest were members of six of the eight
species most commonly recovered from the vaginas of healthy premenopausal women,
namely, Lactobacillus jensenii, L. casei, L. rhamnosus, L. acidophilus, L.
plantarum, and L. fermentum. Six main groupings were identified on the basis of
ribotyping. This technique was able to classify fresh isolates to the species
level. In the case of the ribotype A grouping for L. rhamnosus, differences
between strains were evident by chromosome typing (chromotyping). Many isolates
did not possess plasmids. Six L. rhamnosus strains isolated from four different
health food products appeared to be identical to L. rhamnosus ATCC 21052. The
molecular typing system is useful for identifying and differentiating
Lactobacillus isolates. Studies of strains of potential importance to the
urogenital flora should include molecular characterization as a means of
comparing genetic traits with those of strains whose characteristics associated
with colonization and antagonism against pathogens have been defined.
PMID- 9647810
TI - Cloning and characterization of the lactococcal plasmid-encoded type II
restriction/modification system, LlaDII.
AB - The LlaDII restriction/modification (R/M) system was found on the naturally
occurring 8.9-kb plasmid pHW393 in Lactococcus lactis subsp. cremoris W39. A 2.4
kb PstI-EcoRI fragment inserted into the Escherichia coli-L. lactis shuttle
vector pCI3340 conferred to L. lactis LM2301 and L. lactis SMQ86 resistance
against representatives of the three most common lactococcal phage species: 936,
P335, and c2. The LlaDII endonuclease was partially purified and found to
recognize and cleave the sequence 5'-GC decreases NGC-3', where the arrow
indicates the cleavage site. It is thus an isoschizomer of the commercially
available restriction endonuclease Fnu4HI. Sequencing of the 2.4-kb PstI-EcoRI
fragment revealed two open reading frames arranged tandemly and separated by a
105-bp intergenic region. The endonuclease gene of 543 bp preceded the methylase
gene of 954 bp. The deduced amino acid sequence of the LlaDII R/M system showed
high homology to that of its only sequenced isoschizomer, Bsp6I from Bacillus sp.
strain RFL6, with 41% identity between the endonucleases and 60% identity between
the methylases. The genetic organizations of the LlaDII and Bsp6I R/M systems are
identical. Both methylases have two recognition sites (5'-GCGGC-3' and 5'-GCCGC
3') forming a putative stemloop structure spanning part of the presumed -35
sequence and part of the intervening region between the -35 and -10 sequences.
Alignment of the LlaDII and Bsp6I methylases with other m5C methylases showed
that the protein primary structures possessed the same organization.
PMID- 9647811
TI - Isolation and characterization of phenol-degrading denitrifying bacteria.
AB - Phenol is a man-made as well as a naturally occurring aromatic compound and an
important intermediate in the biodegradation of natural and industrial aromatic
compounds. Whereas many microorganisms that are capable of aerobic phenol
degradation have been isolated, only a few phenol-degrading anaerobic organisms
have been described to date. In this study, three novel nitrate-reducing
microorganisms that are capable of using phenol as a sole source of carbon were
isolated and characterized. Phenol-degrading denitrifying pure cultures were
obtained by enrichment culture from anaerobic sediments obtained from three
different geographic locations, the East River in New York, N.Y., a Florida
orange grove, and a rain forest in Costa Rica. The three strains were shown to be
different from each other based on physiologic and metabolic properties. Even
though analysis of membrane fatty acids did not result in identification of the
organisms, the fatty acid profiles were found to be similar to those of Azoarcus
species. Sequence analysis of 16S ribosomal DNA also indicated that the phenol
degrading isolates were closely related to members of the genus Azoarcus. The
results of this study add three new members to the genus Azoarcus, which
previously comprised only nitrogen-fixing species associated with plant roots and
denitrifying toluene degraders.
PMID- 9647812
TI - Cytoplasmic membrane lipoprotein LppC of Streptococcus equisimilis functions as
an acid phosphatase.
AB - The function of the streptococcal cytoplasmic membrane lipoprotein, LppC, was
identified with isogenic Streptococcus equisimilis H46A and Escherichia coli
JM109 strain pairs differing in whether they contained [H46A and JM109(pLPP2)] or
lacked (H46A lppC::pLPP10 and JM109) the functional lppC gene for comparative
phosphatase determinations under acidic conditions. lppC-directed acid
phosphatase activity was demonstrated zymographically and by specific enzymatic
activity assays, with whole cells or cell membrane preparations as enzyme
sources. LppC acid phosphatase showed optimum activity at pH 5, and the enzyme
activity was unaffected by Triton X-100, L-(+)-tartaric acid, or EDTA. Database
searches revealed significant structural homology of LppC to the Streptococcus
pyogenes LppA, Flavobacterium meningosepticum OplA, Helicobacter pylori HP1285,
and Haemophilus influenzae Hel [e (P4)] proteins. These results suggest a
possible function for these proteins and establish a novel function of
streptococcal cell membrane lipoproteins.
PMID- 9647813
TI - Abundance in sewage of bacteriophages that infect Escherichia coli O157:H7 and
that carry the Shiga toxin 2 gene.
AB - Shiga toxin-converting bacteriophages are involved in the pathogenicity of some
enteric bacteria, such as Escherichia coli O157:H7, but data on the occurrence
and distribution of such phages as free particles in nature were not available.
An experimental approach has been developed to detect the presence of the Shiga
toxin 2 (Stx 2)-encoding bacteriophages in sewage. The Stx 2 gene was amplified
by PCR from phages concentrated from 10-ml samples of sewage. Moreover, the
phages carrying the Stx 2 gene were detected in supernatants from bacteriophage
enrichment cultures by using an Stx 2-negative E. coli O157:H7 strain infected
with phages purified from volumes of sewage as small as 0.02 ml. Additionally,
the A subunit of Stx 2 was detected in the supernatants of the bacteriophage
enrichment cultures, which also showed cytotoxic activity for Vero cells. By
enrichment of phages concentrated from different volumes of sewage and applying
the most-probable-number technique, it was estimated that the number of phages
infectious for E. coli O157:H7 and carrying the Stx 2 gene was in the range of 1
to 10 per ml of sewage from two different origins. These values were
approximately 1% of all phages infecting E. coli O157:H7.
PMID- 9647814
TI - Detection of hemolysin variants of Shiga toxin-producing Escherichia coli by PCR
and culture on vancomycin-cefixime-cefsulodin blood agar.
AB - The presence of a hemolysin-encoding gene, elyA or hlyA, from Shiga toxin
producing Escherichia coli (STEC) was detected by PCR in each of 95 strains
tested. PCR products of elyA from human STEC isolates of serovars frequently
detected in Germany, such as O157:H-, O103:H2, O103:H-, O26:H11, and O26:H-,
showed nucleotide sequences identical to previously reported ones for O157:H7 and
O111:H- strains. Compared to them, four elyA amplicons derived from human
isolates of rare STEC serovars showed identity of about 98% but lacked an AluI
restriction site. However, the nucleotide sequence of an amplicon derived from a
porcine O138:K81:H- STEC strain was identical to the corresponding region of
hlyA, encoding alpha-hemolysin, from E. coli. This hlyA amplicon showed 68%
identity with the nucleotide sequence of the corresponding elyA fragment. It
differed from the elyA PCR product in restriction fragments generated by AluI,
EcoRI, and MluI. Of the 95 representative STEC strains, 88 produced hemolysin on
blood agar supplemented with vancomycin (30 mg/liter), cefixime (20
micrograms/liter), and cefsulodin (3 mg/liter) (BVCC). The lowest added numbers
of two to six STEC CFU per g of stool or per ml of raw milk were detectable on
BVCC plates after seeding of the preenrichment broth, modified tryptic soy broth
(mTSB) supplemented with novobiocin (10 mg/liter), with 16 STEC strains. These
strains represented the seven prevailing serovars diagnosed from German patients.
However, with ground-beef samples, PCR was essential to identify the lowest added
numbers of two to six STEC CFU among colonies of hemolyzing Enterobacteriaceae,
such as Serratia spp. and alpha-hemolysin-producing E. coli. We conclude that
preenrichment of stool and food samples in mTSB for 6 h followed by overnight
culturing on BVCC is a simple method for the isolation and presumptive
identification of STEC.
PMID- 9647815
TI - Construction and use of an ipb DNA module to generate Pseudomonas strains with
constitutive trichloroethene and isopropylbenzene oxidation activity.
AB - Pseudomonas sp. strain JR1 exhibits trichloroethene (TCE) oxidation activity with
isopropylbenzene (IPB) as the inducer substrate. We previously reported the genes
encoding the first three enzymes of the IPB-degradative pathway (ipbA1, ipbA2,
ipbA3, ipbA4, ipbB, and ipbC) and identified the initial IPB dioxygenase (IpbA1
A2A3A4) as responsible for TCE cooxidation (U. Pflugmacher, B. Averhoff, and G.
Gottschalk, Appl. Environ. Microbiol. 62:3967-3977, 1996). Primer extension
analyses revealed multiple transcriptional start points located upstream of the
translational initiation codon of ipbA1. The transcription from these start sites
was found to be IPB dependent. Thirty-one base pairs upstream of the first
transcriptional start point tandemly repeated DNA sequences overlapping the -35
region of a putative sigma 70 promoter were found. These repeats exhibit
significant sequence similarity to the operator-promoter region of the xyl meta
operon in Pseudomonas putida, which is required for the binding of XylS, a
regulatory protein of the XylS (also called AraC) family. These similarities
suggest that the transcription of the IPB dioxygenase genes is modulated by a
regulatory protein of the XylS/AraC family. The construction of an ipb DNA module
devoid of this ipb operator-promoter region and the stable insertion of this DNA
module into the genomes of different Pseudomonas strains resulted in pseudomonads
with constitutive IPB and TCE oxidation activities. Constitutive TCE oxidation of
two such Pseudomonas hybrid strains, JR1A::ipb and CBS-3::ipb, was found to be
stable for more than 120 generations in antibiotic-free medium. Evaluation of
constitutive TCE degradation rates revealed that continuous cultivation of strain
JR1A::ipb resulted in a significant increase in rates of TCE degradation.
PMID- 9647816
TI - Small-Scale DNA Sample Preparation Method for Field PCR Detection of Microbial
Cells and Spores in Soil.
AB - Efficient, nonselective methods to obtain DNA from the environment are needed for
rapid and thorough analysis of introduced microorganisms in environmental samples
and for analysis of microbial community diversity in soil. A small-scale
procedure to rapidly extract and purify DNA from soils was developed for in-the
field use. Amounts of DNA released from bacterial vegetative cells, bacterial
endospores, and fungal conidia were compared by using hot-detergent treatment,
freeze-thaw cycles, and bead mill homogenization. Combining a hot-detergent
treatment with bead mill homogenization gave the highest DNA yields from all
three microbial cell types and provided DNA from the broadest range of microbial
groups in a natural soil community. Only the bead mill homogenization step was
effective for DNA extraction from Bacillus globigii (B. subtilis subsp. niger)
endospores or Fusarium moniliforme conidia. The hot-detergent-bead mill procedure
was simplified and miniaturized. By using this procedure and small-scale, field
adapted purification and quantification procedures, DNA was prepared from four
different soils seeded with Pseudomonas putida cells or B. globigii spores. In a
New Mexico soil, seeded bacterial targets were detected with the same sensitivity
as when assaying pure bacterial DNA (2 to 20 target gene copies in a PCR
mixture). The detection limit of P. putida cells and B. globigii spores in
different soils was affected by the amount of background DNA in the soil samples,
the physical condition of the DNA, and the amount of DNA template used in the
PCR.
PMID- 9647817
TI - Molecular cloning, nucleotide sequence, and expression in Escherichia coli of a
hemolytic toxin (aerolysin) gene from Aeromonas trota.
AB - Aeromonas trota AK2, which was derived from ATCC 49659 and produces the
extracellular pore-forming hemolytic toxin aerolysin, was mutagenized with the
transposon mini-Tn5Km1 to generate a hemolysin-deficient mutant, designated
strain AK253. Southern blotting data indicated that an 8.7-kb NotI fragment of
the genomic DNA of strain AK253 contained the kanamycin resistance gene of mini
Tn5Km1. The 8.7-kb NotI DNA fragment was cloned into the vector pGEM5Zf(-) by
selecting for kanamycin resistance, and the resultant clone, pAK71, showed
aerolysin activity in Escherichia coli JM109. The nucleotide sequence of the aerA
gene, located on the 1.8-kb ApaI-EcoRI fragment, was determined to consist of
1,479 bp and to have an ATG initiation codon and a TAA termination codon. An in
vitro coupled transcription-translation analysis of the 1.8-kb region suggested
that the aerA gene codes for a 54-kDa protein, in agreement with nucleotide
sequence data. The deduced amino acid sequence of the aerA gene product of A.
trota exhibited 99% homology with the amino acid sequence of the aerA product of
Aeromonas sobria AB3 and 57% homology with the amino acid sequences of the
products of the aerA genes of Aeromonas salmonicida 17-2 and A. sobria 33.
PMID- 9647818
TI - A two-component monooxygenase catalyzes both the hydroxylation of p-nitrophenol
and the oxidative release of nitrite from 4-nitrocatechol in Bacillus sphaericus
JS905.
AB - Bacteria that metabolize p-nitrophenol (PNP) oxidize the substrate to 3
ketoadipic acid via either hydroquinone or 1,2,4-trihydroxybenzene (THB);
however, initial steps in the pathway for PNP biodegradation via THB are unclear.
The product of initial hydroxylation of PNP could be either 4-nitrocatechol or 4
nitroresorcinol. Here we describe the complete pathway for aerobic PNP
degradation by Bacillus sphaericus JS905 that was isolated by selective
enrichment from an agricultural soil in India. Washed cells of PNP-grown JS905
released nitrite in stoichiometric amounts from PNP and 4-nitrocatechol.
Experiments with extracts obtained from PNP-grown cells revealed that the initial
reaction is a hydroxylation of PNP to yield 4-nitrocatechol. 4-Nitrocatechol is
subsequently oxidized to THB with the concomitant removal of the nitro group as
nitrite. The enzyme that catalyzed the two sequential monooxygenations of PNP was
partially purified and separated into two components by anion-exchange
chromatography and size exclusion chromatography. Both components were required
for NADH-dependent oxidative release of nitrite from PNP or 4-nitrocatechol. One
of the components was identified as a reductase based on its ability to catalyze
the NAD(P)H-dependent reduction of 2,6-dichlorophenolindophenol and nitroblue
tetrazolium. Nitrite release from either PNP or 4-nitrocatechol was inhibited by
the flavoprotein inhibitor methimazole. Our results indicate that the two
monooxygenations of PNP to THB are catalyzed by a single two-component enzyme
system comprising a flavoprotein reductase and an oxygenase.
PMID- 9647819
TI - Glutamate Biosynthesis in Lactococcus lactis subsp. lactis NCDO 2118
AB - Unlike other lactic acid bacteria, Lactococcus lactis subsp. lactis NCDO 2118 was
able to grow in a medium lacking glutamate and the amino acids of the glutamate
family. Growth in such a medium proceeded after a lag phase of about 2 days and
with a reduced growth rate (0.11 h-1) compared to that in the reference medium
containing glutamate (0.16 h-1). The enzymatic studies showed that a
phosphoenolpyruvate carboxylase activity was present, while the malic enzyme and
the enzymes of the glyoxylic shunt were not detected. As in most anaerobic
bacteria, no alpha-ketoglutarate dehydrogenase activity could be detected, and
the citric acid cycle was restricted to a reductive pathway leading to succinate
formation and an oxidative branch enabling the synthesis of alpha-ketoglutarate.
The metabolic bottleneck responsible for the limited growth rate was located in
this latter pathway. As regards the synthesis of glutamate from alpha
ketoglutarate, no glutamate dehydrogenase was detected. While the glutamate
synthase-glutamine synthetase system was detected at a low level, high
transaminase activity was measured. The conversion of alpha-ketoglutarate to
glutamate by the transaminase, the reverse of the normal physiological direction,
operated with different amino acids as nitrogen donor. All of the enzymes assayed
were shown to be constitutive.
PMID- 9647820
TI - Construction and expression of a bifunctional single-chain antibody against
Bacillus cereus p6ores.
AB - The variable-region genes of monoclonal antibody against Bacillus cereus spores
were cloned from mouse hybridoma cells by reverse transcription-PCR. The heavy-
and light-chain variable-region genes were connected by a 45-base linker DNA to
allow folding of the fusion protein into a functional tertiary structure. For
detection of protein expression, a 10-amino-acid strep tag (biotin-like peptide)
was attached to the C terminus of recombinant antibody as the reporter peptide.
The single-chain antibody construct was inserted into the expression vector and
expressed in Escherichia coli under the control of the T7 RNA polymerase-T7
promoter expression system. The expressed single-chain antibody was detected on
Western blots by using a streptavidin-conjugated enzyme system. This small
recombinant antibody fragment (ca. 28,000 Da by calculation) had B. cereus spore
binding ability and antigen specificity similar to those of its parent native
monoclonal antibody.
PMID- 9647821
TI - Development of a streptavidin-conjugated single-chain antibody that binds
Bacillus cereus spores.
AB - Control of microorganisms such as Bacillus cereus spores is critical to ensure
the safety and a long shelf life of foods. A bifunctional single chain antibody
has been developed for detection and binding of B. cereus T spores. The genes
that encode B. cereus T spore single-chain antibody and streptavidin were
connected for use in immunoassays and immobilization of the recombinant
antibodies. A truncated streptavidin, which is smaller than but has biotin
binding ability similar to that of streptavidin, was used as the affinity domain
because of its high and specific affinity with biotin. The fusion protein gene
was expressed in Escherichia coli BL21 (DE3) with the T7 RNA polymerase-T7
promoter expression system. Immunoblotting revealed an antigen specificity
similar to that of its parent native monoclonal antibody. The single-chain
antibody-streptavidin fusion protein can be used in an immunoassay of B. cereus
spores by applying a biotinylated enzyme detection system. The recombinant
antibodies were immobilized on biotinylated magnetic beads by taking advantage of
the strong biotin-streptavidin affinity. Various liquids were artificially
contaminated with 5 x 10(4) B. cereus spores per ml. Greater than 90% of the B.
cereus spores in phosphate buffer or 37% of the spores in whole milk were tightly
bound and removed from the liquid phase by the immunomagnetic beads.
PMID- 9647822
TI - Quantification of Gordona amarae strains in foaming activated sludge and
anaerobic digester systems with oligonucleotide hybridization probes.
AB - Previous studies have shown the predominance of mycolic acid-containing
filamentous actinomycetes (mycolata) in foam layers in activated sludge systems.
Gordona (formerly Nocardia) amarae often is considered the major representative
of this group in activated sludge foam. In this study, small-subunit rRNA genes
of four G. amarae strains were sequenced, and the resulting sequences were
compared to the sequence of G. amarae type strain SE-6. Comparative sequence
analysis showed that the five strains used represent two lines of evolutionary
descent; group 1 consists of strains NM23 and ASAC1, and group 2 contains strains
SE-6, SE-102, and ASF3. The following three oligonucleotide probes were designed:
a species-specific probe for G. amarae, a probe specific for group 1, and a probe
targeting group 2. The probes were characterized by dissociation temperature and
specificity studies, and the species-specific probe was evaluated for use in
fluorescent in situ hybridizations. By using the group-specific probes, it was
possible to place additional G. amarae isolates in their respective groups. The
probes were used along with previously designed probes in membrane hybridizations
to determine the abundance of G. amarae, group 1, group 2, bacterial, mycolata,
and Gordona rRNAs in samples obtained from foaming activated sludge systems in
California, Illinois, and Wisconsin. The target groups were present in
significantly greater concentrations in activated sludge foam than in mixed
liquor and persisted in anaerobic digesters. Hybridization results indicated that
the presence of certain G. amarae strains may be regional or treatment plant
specific and that previously uncharacterized G. amarae strains may be present in
some systems.
PMID- 9647823
TI - Sequencing and characterization of the xyl operon of a gram-positive bacterium,
Tetragenococcus halophila.
AB - The xyl operon of a gram-positive bacterium, Tetragenococcus halophila
(previously called Pediococcus halophilus), was cloned and sequenced. The DNA was
about 7.7 kb long and contained genes for a ribose binding protein and part of a
ribose transporter, xylR (a putative regulatory gene), and the xyl operon, along
with its regulatory region and transcription termination signal, in this order.
The DNA was AT rich, the GC content being 35.8%, consistent with the GC content
of this gram-positive bacterium. The xyl operon consisted of three genes, xylA,
encoding a xylose isomerase, xylB, encoding a xylulose kinase, and xylE, encoding
a xylose transporter, with predicted molecular weights of 49,400, 56,400, and
51,600, respectively. The deduced amino acid sequences of the XylR, XylA, XylB,
and XylE proteins were similar to those of the corresponding proteins in other
gram-positive and -negative bacteria, the similarities being 37 to 64%. Each
polypeptide of XylB and XylE was expressed functionally in Escherichia coli. XylE
transported D-xylose in a sodium ion-dependent manner, suggesting that it is the
first described xylose/Na+ symporter. The XylR protein contained a consensus
sequence for binding catabolites of glucose, such as glucose-6-phosphate, which
has been discovered in glucose and fructose kinases in bacteria. Correspondingly,
the regulatory region of this operon contained a putative binding site of XylR
with a palindromic structure. Furthermore, it contained a consensus sequence, CRE
(catabolite-responsive element), for binding CcpA (catabolite control protein A).
We speculate that the transcriptional regulation of this operon resembles the
regulation of catabolite-repressible operons such as the amy, lev, xyl, and gnt
operons in various gram-positive bacteria. We discuss the significance of the
regulation of gene expression of this operon in T. halophila.
PMID- 9647824
TI - Cloning of a Sphingomonas paucimobilis SYK-6 gene encoding a novel oxygenase that
cleaves lignin-related biphenyl and characterization of the enzyme.
AB - Sphingomonas paucimobilis SYK-6 transforms 2,2'-dihydroxy-3,3'-dimethoxy-5,5'
dicarboxybiphenyl (DDVA), a lignin-related biphenyl compound, to 5
carboxyvanillic acid via 2,2',3-trihydroxy-3'-methoxy-5,5'-dicarboxybiphenyl (OH
DDVA) as an intermediate (15). The ring fission of OH-DDVA is an essential step
in the DDVA degradative pathway. A 15-kb EcoRI fragment isolated from the cosmid
library complemented the growth deficiency of a mutant on OH-DDVA. Subcloning and
deletion analysis showed that a 1.4-kb DNA fragment included the gene responsible
for the ring fission of OH-DDVA. An open reading frame encoding 334 amino acids
was identified and designated ligZ. The deduced amino acid sequence of LigZ had
18 to 21% identity with the class III extradiol dioxygenase family, including the
beta subunit (LigB) of protocatechuate 4,5-dioxygenase of SYK-6 (Y. Noda, S.
Nishikawa, K.-I. Shiozuka, H. Kadokura, H. Nakajima, K. Yano, Y. Katayama, N.
Morohoshi, T. Haraguchi, and M. Yamasaki, J. Bacteriol. 172:2704-2709, 1990),
catechol 2,3-dioxygenase I (MpcI) of Alcaligenes eutrophus JMP222 (M. Kabisch and
P. Fortnagel, Nucleic Acids Res. 18:3405-3406, 1990), the catalytic subunit of
the meta-cleavage enzyme (CarBb) for 2'-aminobiphenyl-2,3-diol from Pseudomonas
sp. strain CA10 (S. I. Sato, N. Ouchiyama, T. Kimura, H. Nojiri, H. Yamane, and
T. Omori, J. Bacteriol. 179:4841-4849, 1997), and 2,3-dihydroxyphenylpropionate
1,2-dioxygenase (MhpB) of Escherichia coli (E. L. Spence, M. Kawamukai, J.
Sanvoisin, H. Braven, and T. D. H. Bugg, J. Bacteriol. 178:5249-5256, 1996). The
ring fission product formed from OH-DDVA by LigZ developed a yellow color with an
absorption maximum at 455 nm, suggesting meta cleavage. Thus, LigZ was concluded
to be a ring cleavage extradiol dioxygenase. LigZ activity was detected only for
OH-DDVA and 2,2',3,3'-tetrahydroxy-5,5'-dicarboxybiphenyl and was dependent on
the ferrous ion.
PMID- 9647825
TI - Molecular Analysis of Bacterial Communities in a Three-Compartment Granular
Activated Sludge System Indicates Community-Level Control by Incompatible
Nitrification Processes.
AB - Bacterial community structure and the predominant nitrifying activities and
populations in each compartment of a three-compartment activated sludge system
were determined. Each compartment was originally inoculated with the same
activated sludge community entrapped in polyethylene glycol gel granules, and
ammonium nitrogen was supplied to the system in an inorganic salts solution at a
rate of 5.0 g of N liter of granular activated sludge-1 day-1. After 150 days of
operation, the system was found to comprise a series of sequential nitrifying
reactions (K. Noto, T. Ogasawara, Y. Suwa, and T. Sumino, Water Res. 32:769-773,
1998), presumably mediated by different bacterial populations. Activity data
showed that all NH4-N was completely oxidized in compartments one and two
(approximately half in each), but no significant nitrite oxidation was observed
in these compartments. In contrast, all available nitrite was oxidized to nitrate
in compartment three. To study the microbial populations and communities in this
system, total bacterial DNA isolated from each compartment was analyzed for
community structure based on the G+C contents of the component populations.
Compartment one showed dominant populations having 50 and 67% G+C contents.
Compartment two was similar in structure to compartment one. The bacterial
community in compartment three had dominant populations with 62 and 67% G+C
contents and retained the 50% G+C content population only at a greatly diminished
level. The 50% G+C content population from compartment one hybridized strongly
with amo (ammonia monooxygenase) and hao (hydroxylamine oxidoreductase) gene
probes from Nitrosomonas europaea. However, the 50% G+C content population from
compartment two hybridized strongly with the hao probe but only weakly with the
amo probe, suggesting that the predominant ammonia-oxidizing populations in
compartments one and two might be different. Since different activities and
populations come to dominate in each compartment from an identical inoculum, it
appears that the nitrification processes may be somewhat incompatible, resulting
in a series of sequential reactions and different communities in this three
compartment system.
PMID- 9647826
TI - Kinetic Parameters of Denitrification in a River Continuum.
AB - Kinetic parameters for nitrate reduction in intact sediment cores were
investigated by using the acetylene blockage method at five sites along the Swale
Ouse river system in northeastern England, including a highly polluted tributary,
R. Wiske. The denitrification rate in sediment containing added nitrate exhibited
a Michaelis-Menten-type curve. The concentration of nitrate for half-maximal
activity (Kmap) by denitrifying bacteria increased on passing downstream from
13.1 to 90.4 uM in the main river, but it was highest (640 uM) in the Wiske. The
apparent maximal rate (Vmaxap) ranged between 35.8 and 324 umol of N m-2 h-1 in
the Swale-Ouse (increasing upstream to downstream), but it was highest in the
Wiske (1,194 umol N m-2 h-1). A study of nitrous oxide (N2O) production at the
same time showed that rates ranged from below the detection limit (0.05 umol of
N2O-N m-2 h-1) at the headwater site to 27 umol of N2O-N m-2 h-1 at the
downstream site. In the Wiske the rate was up to 570 umol of N2O-N m-2 h-1,
accounting for up to 80% of total N gas production.
PMID- 9647827
TI - Increase in Endogenous and Exogenous Cyclic AMP Levels Inhibits Sclerotial
Development in Sclerotinia sclerotiorum.
AB - Growth and development of a wild-type Sclerotinia sclerotiorum isolate were
examined in the presence of various pharmacological compounds to investigate
signal transduction pathways that influence the development of sclerotia.
Compounds known to increase endogenous cyclic AMP (cAMP) levels in other
organisms by inhibiting phosphodiesterase activity (caffeine and 3-isobutyl-1
methyl xanthine) or by activating adenylate cyclase (NaF) reduced or eliminated
sclerotial development in S. sclerotiorum. Growth in the presence of 5 mM
caffeine correlated with increased levels of endogenous cAMP in mycelia. In
addition, incorporation of cAMP into the growth medium decreased or eliminated
the production of sclerotia in a concentration-dependent manner and increased the
accumulation of oxalic acid. Inhibition of sclerotial development was cAMP
specific, as exogenous cyclic GMP, AMP, and ATP did not influence sclerotial
development. Transfer of developing cultures to cAMP-containing medium at
successive time points demonstrated that cAMP inhibits development prior to or
during sclerotial initiation. Together, these results indicate that cAMP plays a
role in the early transition between mycelial growth and sclerotial development.
PMID- 9647828
TI - A highly selective PCR protocol for detecting 16S rRNA genes of the genus
Pseudomonas (sensu stricto) in environmental samples.
AB - Pseudomonas species are plant, animal, and human pathogens; exhibit plant
pathogen-suppressing properties useful in biological control; or express
metabolic versatilities valued in biotechnology and bioremediation. Specific
detection of Pseudomonas species in the environment may help us gain a more
complete understanding of the ecological significance of these microorganisms.
The objective of this study was to develop a PCR protocol for selective detection
of Pseudomonas (sensu stricto) in environmental samples. Extensive database
searches identified a highly selective PCR primer pair for amplification of
Pseudomonas 16S rRNA genes. A protocol that included PCR amplification and
restriction analysis, a general cloning and sequencing strategy, and phylogenetic
analyses was developed. The PCR protocol was validated by testing 50 target and
14 nontarget pure cultures, which confirmed the selectivity to 100%. Further
validation used amplification of target sequences from purified bulk soil DNA
followed by cloning of PCR products. Restriction analysis with HaeIII revealed
eight different fragmentation patterns among 36 clones. Sequencing and
phylogenetic analysis of 8 representative clones indicated that 91.7% of the
products were derived from target organisms of the PCR protocol. Three patterns,
representing only 8.3% of the 36 clones, were derived from non-Pseudomonas or
chimeric PCR artifacts. Three patterns, representing 61.1% of the clones,
clustered with sequences of confirmed Pseudomonas species, whereas two patterns,
representing 30.6% of the clones, formed a novel phylogenetic cluster closely
associated with Pseudomonas species. The results indicated that the Pseudomonas
selective PCR primers were highly specific and may represent a powerful tool for
Pseudomonas population structure analyses and taxonomic confirmations.
PMID- 9647829
TI - Use of green fluorescent protein to tag and investigate gene expression in marine
bacteria.
AB - Two broad-host-range vectors previously constructed for use in soil bacteria (A.
G. Matthysse, S. Stretton, C. Dandie, N. C. McClure, and A. E. Goodman, FEMS
Microbiol. Lett. 145:87-94, 1996) were assessed by epifluorescence microscopy for
use in tagging three marine bacterial species. Expression of gfp could be
visualized in Vibrio sp. strain S141 cells at uniform levels of intensity from
either the lac or the npt-2 promoter, whereas expression of gfp could be
visualized in Psychrobacter sp. strain SW5H cells at various levels of intensity
only from the npt-2 promoter. Green fluorescent protein (GFP) fluorescence was
not detected in the third species, Pseudoalteromonas sp. strain S91, when the gfp
gene was expressed from either promoter. A new mini-Tn10-kan-gfp transposon was
constructed to investigate further the possibilities of fluorescence tagging of
marine bacteria. Insertion of mini-Tn10-kan-gfp generated random stable mutants
at high frequencies with all three marine species. With this transposon, strongly
and weakly expressed S91 promoters were isolated. Visualization of GFP by
epifluorescence microscopy was markedly reduced when S91 (mini-Tn10-kan-gfp)
cells were grown in rich medium compared to that when cells were grown in minimal
medium. Mini-Tn10-kan-gfp was used to create an S91 chitinase-negative, GFP
positive mutant. Expression of the chi-gfp fusion was induced in cells exposed to
N'-acetylglucosamine or attached to chitin particles. By laser scanning confocal
microscopy, biofilms consisting of microcolonies of chi-negative, GFP+ S91 cells
were found to be localized several microns from a natural chitin substratum.
Tagging bacterial strains with GFP enables visualization of, as well as
monitoring of gene expression in, living single cells in situ and in real time.
PMID- 9647830
TI - Spatial and temporal variation of phenanthrene-degrading bacteria in intertidal
sediments.
AB - Phenanthrene-degrading bacteria were isolated from a 1-m2 intertidal sediment
site in Boston Harbor. Samples were taken six times over 2 years. A total of 432
bacteria were isolated and characterized by biochemical testing. When clustered
on the basis of phenotypic characteristics, the isolates could be separated into
68 groups at a similarity level of approximately 70%. Several groups (a total of
200 isolates) corresponded to well-characterized species belonging the genera
Vibrio and Pseudomonas. Only 51 of the 437 isolates (< 11.7% of the total)
hybridized to a DNA probe that encodes the upper pathway of naphthalene and
phenanthrene degradation in Pseudomonas putida NCIB 9816. A cluster analysis
indicated that the species composition of the phenanthrene-degrading community
changed significantly from sampling date to sampling date. At one sampling time,
12 6-mm-diameter core subsamples were taken within the 1-m2 site to determine the
spatial variability of the degrading communities. An analysis of molecular
variance, performed with the phenotypic characteristics, indicated that only 6%
of the variation occurred among the 12 subsamples, suggesting that the subsamples
were almost identical in composition. We concluded that the communities of
phenanthrene-degrading bacteria in the sediments are very diverse, that the
community structure undergoes significant change with time but does not vary
significantly on a spatial scale of centimeters, and that the predominant genes
that encode phenanthrene degradation in the communities are not well
characterized.
PMID- 9647831
TI - Aerobic mineralization of 2,6-dichlorophenol by Ralstonia sp. strain RK1.
AB - A new aerobic bacterium was isolated from the sediment of a freshwater pond close
to a contaminated site at Amponville (France). It was enriched in a fixed-bed
reactor fed with 2,6-dichlorophenol (2,6-DCP)as the sole carbon and energy source
at pH 7.5 and room temperature. The degradation of 2,6-DCP followed Monod
kinetics at low initial concentrations. At concentrations above 300 microM (50
mg.liter-1), 2,6-DCP increasingly inhibited its own degradation. The base
sequence of the 16S ribosomal DNA allowed us to assign the bacterium to the genus
Ralstonia (formerly Alcaligenes). The substrate spectrum of the bacterium
includes toluene, benzene, chlorobenzene, phenol, and all four ortho- and para
substituted mono- and dichlorophenol isomers. Substituents other than chlorine
prevented degradation. The capacity to degrade 2,6-DCP was examined in two fixed
bed reactors. The microbial population grew on and completely mineralized 2,6-DCP
at 2,6-DCP concentrations up to 740 microM in continuous reactor culture supplied
with H2O2 as an oxygen source. Lack of peroxide completely stopped further
degradation of 2,6-DCP. Lowering the acid-neutralizing capacity of the medium to
1/10th the original capacity led to a decrease in the pH of the effluent from 7
to 6 and to a significant reduction in the degradation activity. A second fixed
bed reactor successfully removed low chlorophenol concentrations (20 to 26
microM) with hydraulic residence times of 8 to 30 min.
PMID- 9647832
TI - Capillary Electrophoresis Measurements of Electrophoretic Mobility for Colloidal
Particles of Biological Interest.
AB - The electrophoretic mobilities of three bacterial strains were investigated by
capillary electrophoresis (CE) and were compared with results obtained by
microelectrophoresis (ME). The CE measurements yielded bimodal electropherograms
for two of the strains, thus illustrating for the first time that surface charge
variations within a monoclonal population can be probed by CE. Intrapopulation
variations were not detected by ME. The mobilities of three chemically distinct
types of latex microspheres were also measured. Differences between the mean
mobilities obtained by CE and ME were not statistically significant (P = 0.50);
the standard deviations of the CE measurements were typically 2 to 10 times
smaller than those obtained by comparable ME measurements. The reproducibility of
CE permitted batch-to-batch mobility variations to be probed for the bacteria
(one of the strains exhibited such variations), and aggregation was evident in
one of the latex suspensions. These effects were not measurable with ME.
PMID- 9647833
TI - Biodegradation of variable-chain-length alkanes at low temperatures by a
psychrotrophic Rhodococcus sp.
AB - The psychorotrophic Rhodococcus sp. strain Q15 was examined for its ability to
degrade individual n-alkanes and diesel fuel at low temperatures, and its alkane
catabolic pathway was investigated by biochemical and genetic techniques. At 0
and 5 degrees C, Q15 mineralized the short-chain alkanes dodecane and hexadecane
to a greater extent than that observed for the long-chain alkanes octacosane and
dotriacontane. Q15 utilized a broad range of aliphatics (C10 to C21 alkanes,
branched alkanes, and a substituted cyclohexane) present in diesel fuel at 5
degrees C. Mineralization of hexadecane at 5 degrees C was significantly greater
in both hydrocarbon-contaminated and pristine soil microcosms seeded with Q15
cells than in uninoculated control soil microcosms. The detection of hexadecane
and dodecane metabolic intermediates (1-hexadecanol and 2-hexadecanol and 1
dodecanol and 2-dodecanone, respectively) by solid-phase microextraction-gas
chromatography-mass spectrometry and the utilization of potential metabolic
intermediates indicated that Q15 oxidizes alkanes by both the terminal oxidation
pathway and the subterminal oxidation pathway. Genetic characterization by PCR
and nucleotide sequence analysis indicated that Q15 possesses an aliphatic
aldehyde dehydrogenase gene highly homologous to the Rhodococcus erythropolis the
A gene. Rhodococcus sp. strain Q15 possessed two large plasmids of approximately
90 and 115 kb (shown to mediate Cd resistance) which were not required for alkane
mineralization, although the 90-kb plasmid enhanced mineralization of some
alkanes and growth on diesel oil at both 5 and 25 degrees C.
PMID- 9647834
TI - Seasonal and spatial variability of bacterial and archaeal assemblages in the
coastal waters near Anvers Island, Antarctica.
AB - A previous report of high levels of members of the domain Archaeal in Antarctic
coastal waters prompted us to investigate the ecology of Antarctic planktonic
prokaryotes. rRNA hybridization techniques and denaturing gradient gel
electrophoresis (DGGE) analysis of the bacterial V3 region were used to study
variation in Antarctic picoplankton assemblages. In Anvers Island nearshore
waters during late winter to early spring, the amounts of archaeal rRNA ranged
from 17.1 to 3.6% of the total picoplankton rRNA in 1996 and from 16.0 to 1.0% of
the total rRNA in 1995. Offshore in the Palmer Basin, the levels of archaeal rRNA
throughout the water column were higher (average, 24% of the total rRNA) during
the same period in 1996. The archaeal rRNA levels in nearshore waters followed a
highly seasonal pattern and markedly decreased during the austral summer at two
stations. There was a significant negative correlation between archaeal rRNA
levels and phytoplankton levels (as inferred from chlorophyll a concentrations)
in nearshore surface waters during the early spring of 1995 and during an 8-month
period in 1996 and 1997. In situ hybridization experiments revealed that 5 to 14%
of DAPI (4',6-diamidino-2-phenylindole)-stained cells were archaeal,
corresponding to 0.9 x 10(4) to 2.7 x 10(4) archaeal cells per ml, in late winter
1996 samples. Analysis of bacterial ribosomal DNA fragments by DGGE revealed that
the assemblage composition may reflect changes in water column stability, depth,
or season. The data indicate that changes in Antarctic seasons are accompanied by
significant shifts in the species composition of bacterioplankton assemblages and
by large decrease in the relative proportion of archaeal rRNA in the nearshore
water column.
PMID- 9647835
TI - Distribution of Clostridium perfringens and fecal sterols in a benthic coastal
marine environment influenced by the sewage outfall from McMurdo Station,
Antarctica.
AB - The spatial distribution, movement, and impact of the untreated wastewater
outfall from McMurdo Station, Antarctica, were investigated under early austral
summer conditions. The benthic environment was examined to determine the
distribution of Clostridium perfringens in sediment cores and the intestinal
contents of native invertebrates and fish along a transect of stations. These
stations extended ca. 411 m south of the outfall. The findings revealed that the
concentration of C. perfringens decreased with depth in the sediment and distance
from the outfall. High percentages of tunicates and sea urchins were colonized
with this bacterium along the transect. Coprostanol concentrations were also
measured in sediment samples taken from each of the transect stations, and a
similar trend was observed. These results are in agreement with the findings of
previous studies performed with the water column and collectively provide
evidence that the disposal of domestic wastes deserves special consideration in
polar marine environments.
PMID- 9647836
TI - phnE and glpT genes enhance utilization of organophosphates in Escherichia coli K
12.
AB - Wild-type Escherichia coli K-12 strain JA221 grows poorly on low concentrations
(< or = 1 mM) of diisopropyl fluorophosphate and its hydrolysis product,
diisopropyl phosphate (DIPP), as sole phosphorus sources. Spontaneous
organophosphate utilization (OPU) mutants were isolated that efficiently utilized
these alternate sources of phosphate. A genomic library was constructed from one
such OPU mutant, and two genes were isolated that conferred the OPU phenotype to
strain JA221 upon transformation. These genes were identified as phnE and glpT.
The original OPU mutation represented phnE gene activation and corresponded to
the same 8-bp unit deletion from the cryptic wild-type E. coli K-12 phnE gene
that has been shown previously to result in phnE activation. In comparison,
sequence analysis revealed that the observed OPU phenotype conferred by the glpT
gene was not the result of a mutation. PCR clones of glpT from both the mutant
and the wild type were found to confer the OPU phenotype to JA221 when they were
present on the high-copy-number pUC19 plasmid but not when they were present on
the low-copy-number pWSK29 plasmid. This suggests that the OPU phenotype
associated with the glpT gene is the result of amplification and overproduction
of the glpT gene product. Both the active phnE and multicopy glpT genes
facilitated effective metabolism of low concentrations of DIPP, whereas only the
active phnE gene could confer the ability to break down a chromogenic substrate,
5-bromo-4-chloro-3-indoxyl phosphate-p-toluidine (X-Pi). This result indicates
that in E. coli, X-Pi is transported exclusively by the Phn system, whereas DIPP
(or its metabolite) may be transported by both Phn and Glp systems.
PMID- 9647838
TI - Modeling of Growth of Lactobacillus sanfranciscensis and Candida milleri in
Response to Process Parameters of Sourdough Fermentation.
AB - We investigated the effect of the ecological factors pH, temperature, ionic
strength, and lactate, acetate, and ethanol levels on Candida milleri and two
strains of Lactobacillus sanfranciscensis, organisms representative of the
microflora of sourdough. A mathematical model describing the single and combined
effects of these factors on the growth of these organisms was established in
accordance with the following criteria: quality of fit, biological significance
of the parameters, and applicability of the in vitro data to in situ processes.
The growth rates of L. sanfranciscensis LTH1729 and LTH2581 were virtually
identical under all conditions tested. These organisms tolerated >160 mmol of
undissociated acetic acid per liter. Growth occurred in the pH range of 3.9 to
6.7 and was completely inhibited by 4% NaCl. C. milleri had a lower optimum
temperature for growth (27 degreesC) than the lactobacilli. The growth of the
yeast was not affected by pH in the range of 3.5 to 7, and up to 8% NaCl was
tolerated. Complete inhibition of growth occurred at 150 mmol of undissociated
acetic acid per liter, but acetate at concentrations of up to 250 mmol/liter
exerted virtually no effect. The model provides insight into factors contributing
to the stability of the sourdough microflora and can facilitate the design of
novel sourdough processes.
PMID- 9647837
TI - Cloning and expression of the inositol monophosphatase gene from Methanococcus
jannaschii and characterization of the enzyme.
AB - Inositol monophosphatase (EC 3.1.3.25) plays a pivotal role in the biosynthesis
of di-myo-inositol-1,1'-phosphate, an osmolyte found in hyperthermophilic
archaeal. Given the sequence homology between the MJ109 gene product of
Methanococcus jannaschii and human inositol monophosphatase, the MJ109 gene was
cloned and expressed in Escherichia coli and examined for inositol
monophosphatase activity. The purified MJ109 gene product showed inositol
monophosphatase activity with kinetic parameters (K(m) = 0.091 +/- 0.016 mM; Vmax
= 9.3 +/- 0.45 mumol of Pi min-1 mg of protein-1) comparable to those of
mammalian and E. coli enzymes. Its substrate specificity, Mg2+ requirement, Li+
inhibition, subunit association (dimerization), and heat stability were studied
and compared to those of other inositol monophosphatases. The lack of inhibition
by low concentrations of Li+ and high concentrations of Mg2+ and the high rates
of hydrolysis of glucose-1-phosphate and p-nitrophenylphosphate are the most
pronounced differences between the archaeal inositol monophosphatase and those
from other sources. The possible causes of these kinetic differences are
discussed, based on the active site sequence alignment between M. jannaschii and
human inositol monophosphatase and the crystal structure of the mammalian enzyme.
PMID- 9647839
TI - Cloning of Phanerochaete chrysosporium leu2 by complementation of bacterial
auxotrophs and transformation of fungal auxotrophs.
AB - A Phanerochaete chrysosporium cDNA library was constructed in an expression
vector that allows expression in both Escherichia coli and Saccharomyces
cerevisiae. This expression vector, lambda YES, contains the lacZ promoter for
expression in E. coli and the GAL1 promoter for expression in yeast. A number of
genes were cloned by complementation of bacterial amino acid auxotrophs. The cDNA
encoding the beta-isopropylmalate dehydrogenase from P. chrysosporium was
characterized further. The genomic clone (gleu2) was subsequently isolated and
was used successfully as a selectable marker to transform P. chrysosporium
auxotrophs for LEU2. Protoplasts for transformation were prepared with readily
obtained conidiospores rather than with basidiospores, which were used in
previous P. chrysosporium transformation procedures. The method described here
allows other genes to be isolated from P. chrysosporium for use as selectable
markers.
PMID- 9647840
TI - Trifolitoxin Production Increases Nodulation Competitiveness of Rhizobium etli
CE3 under Agricultural Conditions.
AB - A major barrier to the use of nitrogen-fixing inoculum strains for the
enhancement of legume productivity is the inability of commercially available
strains to compete with indigenous rhizobia for nodule formation. Despite
extensive research on nodulation competitiveness, there are no examples of field
efficacy studies of strains that have been genetically improved for nodulation
competitiveness. We have shown previously that production of the peptide
antibiotic trifolitoxin (TFX) by Rhizobium etli results in significantly
increased nodule occupancy values in nonsterile soil in growth chamber
experiments (E. A. Robleto, A. J. Scupham, and E. W. Triplett, Mol. Plant-Microbe
Interact. 10:228-233, 1997). To determine whether TFX production by Rhizobium
etli increases nodulation competitiveness in field-grown plants, seeds of
Phaseolus vulgaris were inoculated with mixtures of Rhizobium etli strains at
different ratios. The three nearly isogenic inoculum strains used included TFX
producing and non-TFX-producing strains, as well as a TFX-sensitive reference
strain. Data was obtained over 2 years for nodule occupancy and over 3 years for
assessment of the effect of the TFX production phenotype on grain yield. In
comparable mixtures in which the test strain accounted for between 5 and 50% of
the inoculum, the TFX-producing strain exhibited at least 20% greater nodule
occupancy than the non-TFX-producing strain in both years. The TFX production
phenotype had no effect on grain yield over 3 years; the average yields reached
2,400 kg/ha. These results show that addition of the TFX production phenotype
significantly increases nodule occupancy under field conditions without adverse
effects on grain yield. As we used common inoculation methods in this work, there
are no practical barriers to the commercial adoption of the TFX system for
agriculture.
PMID- 9647841
TI - Effect of Insertion Site and Metabolic Load on the Environmental Fitness of a
Genetically Modified Pseudomonas fluorescens Isolate.
AB - An isolate of Pseudomonas fluorescens (SBW25) was modified with different marker
genes (lacZY, aph-1, and xylE). These marker genes were inserted singly or in
combination into two separate (1 Mbp apart) and presumably nonessential sites (-6
and Ee) on the chromosome of SBW25. This allowed the production of a range of
genetically modified SBW25 variants that differed with respect to insertion site
of the marker genes and metabolic burden. The environmental fitness of the
different SBW25 variants was tested in soil, in the rhizosphere of wheat and pea,
and on the phylloplane of wheat. Reduced environmental fitness of the different
variants was mainly attributed to the extra metabolic burden of novel gene
expression, whereas choice of insertion site was of little significance. Changes
in environmental fitness were dependent on the environmental conditions; an
environment, such as soil, with a low microbial carrying capacity had a negative
effect on the environmental fitness of variants with a large metabolic load. In
environments with a larger carrying capacity, such as the rhizosphere of pea,
environmental fitness of variants with a large metabolic load was not
significantly different from that of variants with a smaller metabolic burden.
PMID- 9647842
TI - Quantification of toxic cyanobacteria in water by use of competitive PCR followed
by sequence-specific labeling of oligonucleotide probes.
AB - A complete nucleic-acid-based assay which consists of sample preparation, DNA
amplification, and chromogenic detection was developed for quantifying potential
toxin-producing cyanobacteria of interest to the public. The sample preparation
strategy involves the same solid phase for cell concentration and DNA
purification. For the detection step, we used a combination of competitive PCR
amplification, sequence-specific labeling of oligonucleotide probes,
hybridization of the labeled oligonucleotides to immobilized complements and,
finally, chromogenic detection. The complete assay was tested with water
containing toxin-producing cyanobacteria belonging to the genus Microcystis. A
detection limit of 100 cells/ml and a quantitative range of more than 3 orders of
magnitude were obtained. This approach can easily be adapted to a wide range of
bacterial species and has the potential for simultaneous detection and
quantitation of several different target organisms by a single assay.
PMID- 9647843
TI - Development of a lipase fermentation process that uses a recombinant Pseudomonas
alcaligenes strain.
AB - Pseudomonas alcaligenes M-1 secretes an alkaline lipase, which has excellent
characteristics for the removal of fatty stains under modern washing conditions.
A fed-batch fermentation process based on the secretion of the alkaline lipase
from P. alcaligenes was developed. Due to the inability of P. alcaligenes to grow
on glucose, citric acid and soybean oil were applied as substrates in the batch
phase and feed phase, respectively. The gene encoding the high-alkaline lipase
from P. alcaligenes was isolated and characterized. Amplification of lipase gene
copies in P. alcaligenes with the aid of low- and high-copy-number plasmids
resulted in an increase of lipase expression that was apparently colinear with
the gene copy number. It was found that overexpression of the lipase helper gene,
lipB, produced a stimulating effect in strains with high copy numbers (> 20) of
the lipase structural gene, lipA. In strains with lipA on a low-copy-number
vector, the lipB gene did not show any effect, suggesting that LipB is required
in a low ratio to LipA only. During scaling up of the fermentation process to 100
m3, severe losses in lipase productivity were observed. Simulations have
identified an increased level of dissolved carbon dioxide as the most probable
cause for the scale-up losses. A large-scale fermentation protocol with a reduced
dissolved carbon dioxide concentration resulted in a substantial elimination of
the scale-up loss.
PMID- 9647844
TI - Intergeneric transfer of conjugative and mobilizable plasmids harbored by
Escherichia coli in the gut of the soil microarthropod Folsomia candida
(Collembola).
AB - The gut of the soil microarthropod Folsomia candida provides a habitat for a high
density of bacterial cells (T. Thimm, A. Hoffmann, H. Borkott, J. C. Munch, and
C. C. Tebbe, Appl. Environ. Microbiol. 64:2660-2669, 1998). We investigated
whether these gut bacteria act as recipients for plasmids from Escherichia coli.
Filter mating with E. coli donor cells and collected feces of F. candida revealed
that the broad-host-range conjugative plasmid pRP4-luc (pRP4 with a luciferase
marker gene) transferred to fecal bacteria at estimated frequencies of 5.4 x 10(
1) transconjugants per donor. The mobilizable plasmid pSUP104-luc was transferred
from the IncQ mobilizing strain E. coli S17-1 and less efficiently from the IncF1
mobilizing strain NM522 but not from the nonmobilizing strain HB101. When S17-1
donor strains were fed to F. candida, transconjugants of pRP4-luc and pSUP104-luc
were isolated from feces. Additionally, the narrow-host-range plasmid pSUP202-luc
was transferred to indigenous bacteria, which, however, could not maintain this
plasmid. Inhibition experiments with nalidixic acid indicated that pRP4-luc
plasmid transfer took place in the gut rather than in the feces. A remarkable
diversity of transconjugants was isolated in this study: from a total of 264
transconjugants, 15 strains belonging to the alpha, beta, or gamma subclass of
the class Proteobacteria were identified by DNA sequencing of the PCR-amplified
16S rRNA genes and substrate utilization assays (Biolog). Except for Alcaligenes
faecalis, which was identified by the Biolog assay, none of the isolates was
identical to reference strains from data banks. This study indicates the
importance of the microarthropod gut for enhanced conjugative gene transfer in
soil microbial communities.
PMID- 9647845
TI - The gut of the soil microarthropod Folsomia candida (Collembola) is a frequently
changeable but selective habitat and a vector for microorganisms.
AB - Interaction potentials between soil microarthropods and microorganisms were
investigated with Folsomia candida (Insecta, Collembola) in microcosm laboratory
experiments. Microscopic analysis revealed that the volumes of the simple, rod
shaped guts of adult specimens varied with their feeding activity, from 0.7 to
11.2 nl. A dense layer of bacterial cells, associated with the peritrophic
membrane, was detected in the midgut by scanning electron microscopy. Depending
on the molting stage, which occurred at intervals of approximately 4 days,
numbers of heterotrophic, aerobic gut bacteria changed from 4.9 x 10(2) to 2.3 x
10(6) CFU per specimen. A total of 11 different taxonomic bacterial groups and
the filamentous fungus Acremonium charticola were isolated from the guts of five
F. candida specimens. The most abundant isolate was related to Erwinia amylovora
(96.2% DNA sequence similarity to its 16S rRNA gene). F. candida preferred to
feed on Pseudomonas putida and three indigenous gut isolates rather than eight
different type culture strains. When luciferase reporter gene-tagged bacterial
strains were pulse fed to F. candida, gut isolates were continuously shed for 8
days to several weeks but Escherichia coli HB101 was shed for only 1 day. Ratios
of ingested to released bacterial cells demonstrated that populations of
nonindigenous gut bacteria like Sinorhizobium meliloti L33 and E. coli HB101 were
reduced by more than 4 orders of magnitude but that the population of gut isolate
Alcaligenes faecalis HR4 was reduced only 500-fold. This work demonstrates that
F. candida represents a frequently changeable but selective habitat for bacteria
in terrestrial environments and that microarthropods have to be considered
factors that modify soil microbial communities.
PMID- 9647846
TI - In Situ Detection of High Levels of Horizontal Plasmid Transfer in Marine
Bacterial Communities.
AB - Gene transfer of the conjugative plasmid pBF1 from Pseudomonas putida to
indigenous bacteria in seawater was investigated with a detection system for gene
transfer based on the green fluorescent protein (GFP) (C. Dahlberg et al., Mol.
Biol. Evol. 15:385-390, 1998). pBF1 was tagged with the gfp gene controlled by a
lac promoter which is down regulated in the donor cell by a chromosomal repressor
(lacIq). The plasmid donor cells (Pseudomonas putida KT2442) subsequently do not
express gfp. Transfer to recipient strains lacking the repressor results in
expression of gfp. The transconjugant can subsequently be detected by
epifluorescence microscopy on a single-cell level. By using this method, transfer
of pBF1::gfp and expression of the gfp gene were first shown to occur during
nutrient-limiting conditions to several defined recipient bacteria in artificial
seawater. Second, we measured transfer of pBF1 from P. putida to the marine
bacterial community directly in seawater samples, on a single-cell level, without
limiting the detection of gene transfer to the culturable fraction of bacteria.
Plasmid transfer was detected on surfaces and in bulk seawater. Seawater bacteria
with different morphologies were shown to receive the plasmid. Gene transfer
frequencies of 2.3 x 10(-6) to 2.2 x 10(-4) transconjugants per recipient were
recorded after 3 days of incubation.
PMID- 9647848
TI - A fluorescent Gram stain for flow cytometry and epifluorescence microscopy.
AB - The fluorescent nucleic acid binding dyes hexidium iodide (HI) and SYTO 13 were
used in combination as a Gram stain for unfixed organisms in suspension. HI
penetrated gram-positive but not gram-negative organisms, whereas SYTO 13
penetrated both. When the dyes were used together, gram-negative organisms were
rendered green fluorescent by SYTO 13; conversely, gram-positive organisms were
rendered red-orange fluorescent by HI, which simultaneously quenched SYTO 13
green fluorescence. The technique correctly predicted the Gram status of 45
strains of clinically relevant organisms, including several known to be gram
variable. In addition, representative strains of gram-positive anaerobic
organisms, normally decolorized during the traditional Gram stain procedure, were
classified correctly by this method.
PMID- 9647847
TI - Increased carotenoid production by the food yeast Candida utilis through
metabolic engineering of the isoprenoid pathway.
AB - The yeast Candida utilis does not possess an endogenous biochemical pathway for
the synthesis of carotenoids. The central isoprenoid pathway concerned with the
synthesis of prenyl lipids is present in C. utilis and active in the biosynthesis
of ergosterol. In our previous study, we showed that the introduction of
exogenous carotenoid genes, crtE, crtB, and crtI, responsible for the formation
of lycopene from the precursor farnesyl pyrophosphate, results in the C. utilis
strain that yields lycopene at 1.1 mg per g (dry weight) of cells (Y. Miura, K.
Kondo, T. Saito, H. Shimada, P. D. Fraser, and N. Misawa, Appl. Environ.
Microbiol. 64:1226-1229, 1998). Through metabolic engineering of the isoprenoid
pathway, a sevenfold increase in the yield of lycopene has been achieved. The
influential steps in the pathway that were manipulated were 3-hydroxy
methylglutaryl coenzyme A (HMG-CoA) reductase, encoded by the HMG gene, and
squalene synthase, encoded by the ERG9 gene. Strains overexpressing the C. utilis
HMG-CoA reductase yielded lycopene at 2.1 mg/g (dry weight) of cells. Expression
of the HMG-CoA catalytic domain alone gave 4.3 mg/g (dry weight) of cells;
disruption of the ERG9 gene had no significant effect, but a combination of ERG9
gene disruption and the overexpression of the HMG catalytic domain yielded
lycopene at 7.8 mg/g (dry weight) of cells. The findings of this study illustrate
how modifications in related biochemical pathways can be utilized to enhance the
production of commercially desirable compounds such as carotenoids.
PMID- 9647849
TI - Specific detection of Legionella pneumophila: construction of a new 16S rRNA
targeted oligonucleotide probe.
AB - Based on comparative sequence analysis, we have designed an oligonucleotide probe
complementary to a region of 16S rRNA of Legionella pneumophila which allows the
differentiation of L. pneumophila from other Legionella species without
cultivation. The specificity of the new probe, LEGPNE1, was tested by in situ
hybridization to a total of four serogroups of six strains of L. pneumophila,
five different Legionella spp. and three nonlegionella species as reference
strains. Furthermore, L. pneumophila cells could be easily distinguished from
Legionella micdadei and Pseudomonas aeruginosa cells by using in situ
hybridization with probes LEGPNE1, LEG705, and EUB338 after infection of the
protozoan Acanthamoeba castellanii.
PMID- 9647850
TI - Microbial Community Composition of Wadden Sea Sediments as Revealed by
Fluorescence In Situ Hybridization.
AB - The microbial community composition of Wadden Sea sediments of the German North
Sea coast was investigated by in situ hybridization with group-specific
fluorescently labeled, rRNA-targeted oligonucleotides. A large fraction (up to
73%) of the DAPI (4',6-diamidino-2-phenylindole)-stained cells hybridized with
the bacterial probes. Nearly 45% of the total cells could be further identified
as belonging to known phyla. Members of the Cytophaga-Flavobacterium cluster were
most abundant in all layers, followed by the sulfate-reducing bacteria.
PMID- 9647851
TI - Effectiveness of SYTOX Green stain for bacterial viability assessment.
AB - The effectiveness of SYTOX Green nucleic acid stain for measuring bacterial
viability was tested on starved populations of Escherichia coli and Salmonella
typhimurium. This stain underestimates the fraction of dead cells within starved
populations containing cells with damaged nucleic acids or membranes. Its
application to natural samples should be considered with caution.
PMID- 9647852
TI - Enhanced broth media for selective growth of Vibrio vulnificus.
AB - Rapid detection of Vibrio vulnificus can be enhanced by optimizing the components
of enrichment broth. PNC (5% peptone, 1% NaCl, and 0.08% cellobiose [pH 8.0])
enhanced the growth of V. vulnificus compared to alkaline peptone broth. PNCC
(PNC with 1.0 to 4.1 U of colistin methanesulfonate per ml) increased the growth
of low levels of V. vulnificus while suppressing non-target bacteria.
PMID- 9647853
TI - Lyme disease Borrelia species in northeastern China resemble those isolated from
far eastern Russia and Japan.
AB - Fifty-nine Borrelia burgdorferi sensu lato culture isolates collected from
northeastern China were characterized by 5S-23S rRNA intergenic spacer
restriction fragment length polymorphism (RFLP) analysis and reactivity with
monoclonal antibodies (MAbs). Among 59 culture isolates, 30 (50.8%) were Borrelia
garinii and 17 (28.8%) were Borrelia afzelii, 2 were mixtures composed of B.
garinii with RFLP pattern B and B. garinii with pattern C, and 9 were mixtures
composed of B. garinii and B. afzelii. One isolate, ChY13p, produced a unique
pattern and was identified as B. garinii based on analyses of 16S rRNA gene
sequence, flagellin PCR-RFLP typing, and MAb reactivities. No Borrelia
burgdorferi sensu stricto or Borrelia japonica isolates were detected. The
results indicate that Lyme disease Borrelia species in northeastern China
resemble those of Borrelia isolates from far eastern Russia and Japan.
PMID- 9647855
TI - Design and Application of Two Rapid Screening Techniques for Isolation of Mn(IV)
Reduction-Deficient Mutants of Shewanella putrefaciens.
AB - Chemical mutagenesis procedures and two newly developed rapid plate assays were
used to identify two Mn(IV) reduction-deficient (Mnr) mutants of Shewanella
putrefaciens. All eleven members of a set of previously isolated Fe(III)
reduction-deficient (Fer) mutants displayed Mnr-positive phenotypes on the plate
assays and were also capable of anaerobic growth on Mn(IV) as the sole terminal
electron acceptor.
PMID- 9647854
TI - Plasposons: modular self-cloning minitransposon derivatives for rapid genetic
analysis of gram-negative bacterial genomes.
AB - A series of modular mini-transposon derivatives which permit the rapid cloning
and mapping of the DNA flanking the minitransposon's site of insertion has been
developed. The basic plasposon, named TnMod, consists of the Tn5 inverted
repeats, a conditional origin of replication, rare restriction endonuclease
multiple cloning sites, and exchangeable antibiotic resistance cassettes. The
broad host range and low target DNA sequence specificity of the Tn5 transposase,
in combination with the flexibility afforded by the modular arrangement of TnMod,
result in a versatile tool for the mapping of insertional mutations and the rapid
recovery of clones from gram-negative bacteria.
PMID- 9647856
TI - Use of luciferase genes as biosensors to study bacterial physiology in the
digestive tract.
AB - A method based on the use of the bacterial luciferase genes was developed in
order to investigate Lactococcus lactis gene expression in the mouse digestive
tract. Germfree mice were monoassociated with different strains containing
transcriptional fusions of promoters with the luciferase genes. Our results
demonstrate that this method is readily applicable to the study of promoter
strength and physiology of bacteria in the digestive tract.
PMID- 9647857
TI - Insecticidal activity of Bacillus laterosporus.
AB - The Bacillus laterosporus strains 921 and 615 were shown to have toxicity for
larvae of the mosquitoes Aedes aegypti, Anopheles stephensi, and Culex pipiens.
The larvicidal activity of B. laterosporus was associated with spores and
crystalline inclusions. Purified B. laterosporus 615 crystals were highly toxic
for Aedes aegypti and Anopheles stephensi.
PMID- 9647858
TI - Phanerochaete flavido-alba Laccase Induction and Modification of Manganese
Peroxidase Isoenzyme Pattern in Decolorized Olive Oil Mill Wastewaters.
AB - Lignin-degrading enzymes were partially purified from supernatant solutions
obtained from Phanerochaete flavido-alba-decolorized olive oil mill wastewaters
(OMW). The dominant enzymes, manganese peroxidases, exhibited different isoform
patterns in decolorized OMW-containing cultures than in residue-free samples.
Laccase induction was also detected in OMW-containing cultures but not in control
cultures.
PMID- 9647859
TI - A chromosomally based tod-luxCDABE whole-cell reporter for benzene, toluene,
ethybenzene, and xylene (BTEX) sensing.
AB - A tod-luxCDABE fusion was constructed and introduced into the chromosome of
Pseudomonas putida F1, yielding the strain TVA8. This strain was used to examine
the induction of the tod operon when exposed to benzene, toluene, ethylbenzene,
and xylene (BTEX) compounds and aqueous solutions of JP-4 jet fuel constituents.
Since this system contained the complete lux cassette (luxCDABE), bacterial
bioluminescence in response to putative chemical inducers of the tod operon was
measured on-line in whole cells without added aldehyde substrate. There was an
increasing response to toluene concentrations from 30 micrograms/liter to 50
mg/liter, which began to saturate at higher concentrations. The detection limit
was 30 micrograms/liter. There was a significant light response to benzene, m-
and p-xylenes, phenol, and water-soluble JP-4 jet fuel components, but there was
no bioluminescence response upon exposure to o-xylene. The transposon insertion
was stable and had no negative effect on cell growth.
PMID- 9647860
TI - Giardia sp. cysts and infectious Cryptosporidium parvum oocysts in the feces of
migratory Canada geese (Branta canadensis).
AB - Fecal droppings of migratory Canada geese, Branta canadensis, collected from nine
sites near the Chesapeake Bay (Maryland), were examined for the presence of
Cryptosporidium parvum and Giardia spp. Cryptosporidium sp. oocysts were found in
feces at seven of nine sites, and Giardia cysts were found at all nine sites. The
oocysts from three sites were infectious for mice and molecularly identified as
the zoonotic genotype of Cryptosporidium parvum. Waterfowl can disseminate
infectious C. parvum oocysts in the environment.
PMID- 9647861
TI - Microbial community changes in a perturbed agricultural soil investigated by
molecular and physiological approaches.
AB - Changes in soil microbial activity and diversity after incubation either with
nitrogen or with a mixture of methane and air were examined. The perturbation by
methane and air were characterized in detail and led to reduced diversity and
enrichment of methanotrophs which were identified by denaturing gradient gel
electrophoresis and 16S rRNA sequencing.
PMID- 9647862
TI - Importance of Extracellular Polymeric Substances from Thiobacillus ferrooxidans
for Bioleaching.
AB - Leaching bacteria such as Thiobacillus ferrooxidans attach to pyrite or sulfur by
means of extracellular polymeric substances (EPS) (lipopolysaccharides). The
primary attachment to pyrite at pH 2 is mediated by exopolymer-complexed
iron(III) ions in an electrochemical interaction with the negatively charged
pyrite surface. EPS from sulfur cells possess increased hydrophobic properties
and do not attach to pyrite, indicating adaptability to the substrate or
substratum.
PMID- 9647863
TI - Gene cloning and characterization of a novel cellulose-binding beta-glucosidase
from Phanerochaete chrysosporium.
AB - Analysis of a 2.4-kb cDNA of the cellulose-binding extracellular beta-glucosidase
(CBGL) from Phanerochaete chrysosporium suggested that CBGL is organized into two
domains, an N-terminal cellulose-binding domain and a C-terminal catalytic
domain. Genomic sequence analysis suggested that cbgl is encoded by 30 exons.
Southern analysis of DNA from homokaryotic cultures indicated that CBGL is
encoded by two alleles, cbgl-1 and cbgl-2, of a single gene.
PMID- 9647864
TI - Microbial characterization of biological filters used for drinking water
treatment.
AB - The impact of preozonation and filter contact time (depth) on microbial
communities was examined in drinking water biofilters treating Ohio River water
which had undergone conventional treatment (coagulation, flocculation,
sedimentation) or solutions of natural organic matter isolated from groundwater
(both ozonated and nonozonated). With respect to filter depth, compared to
filters treating nonozonated waters, preozonation of treated water led to greater
differences in community phospholipid fatty acid (PLFA) profiles, utilization of
sole carbon sources (Biolog), and arbitrarily primed PCR fingerprints. PLFA
profiles indicated that there was a shift toward anaerobic bacteria in the
communities found in the filter treating ozonated water compared to the
communities found in the filter treating nonozonated settled water, which had a
greater abundance of eukaryotic markers.
PMID- 9647865
TI - Basic guide to the mechanisms of antiestrogen action.
AB - Forty years ago, Lerner and coworkers (1958) discovered the first nonsteroidal
antiestrogen and Jensen (Jensen and Jacobson, 1960) identified a target for drug
action, the ER. This knowledge opened the door for the clinical development of
tamoxifen which we now know provides a survival advantage in both node-positive
and node-negative patients with ER-positive disease (Early Breast Cancer
Trialists Collaborative Group, 1992, 1998). The drug has been studied
extensively, and the results have provided an invaluable insight into possible
ancillary advantages of "antiestrogens", i.e., maintenance of bone density and
the prevention of coronary heart disease, and possible disadvantages, i.e., rat
liver carcinogenesis and an increased risk of endometrial cancer. Most
importantly, the identification of the target site-specific actions of tamoxifen
caused a paradigm shift in the prospective uses of antiestrogens from a direct
exploitation of the antitumor properties to the broader application as a
preventative for osteoporosis, but with the beneficial side effects of preventing
breast and endometrial cancer. Raloxifene, a second-generation SERM, has all the
properties in the laboratory that would encourage development as a safe
preventative for osteoporosis (Jordan et al., 1997). As a result, raloxifene has
been evaluated in more than 11,000 postmenopausal women and found to maintain
bone density with significant decreases in breast cancer incidence and no
increase in endometrial thickness. Raloxifene is now available as a preventative
for osteoporosis in postmenopausal women. There is every reason to believe that a
multifaceted agent like raloxifene will find widespread use, and there will be
continuing interest by the pharmaceutical industry in the development of new
agents with even broader applications. The extensive clinical effort is augmented
by past molecular innovations in the laboratory and the future promise of new
discoveries. The cloning and sequencing of the ER (Green et al., 1986; Greene et
al., 1986) has allowed the development of an ER knock-out mouse (Lubahn et al.,
1993) that compliments Jensen's pioneering work (Jensen and Jacobson, 1962) and
describes the consequences of the loss of ER alpha. However, ER beta (Kuiper et
al., 1996), the second ER, has provided an additional dimension to the
description of estrogen and antiestrogen action. For the future, the development
of ER beta monoclonal antibodies, the classification of target sites for the
protein around the body, and the creation of ER beta and ER alpha, beta knock-out
mice will identify new therapeutic targets to modulate physiological functions.
Clearly, the successful crystallization of ER alpha with raloxifene (Brzozowski
et al., 1997) must act as a stimulus for the crystallization of ER beta. The
central issue for research on antiestrogen pharmacology is the discovery of the
mechanism (or mechanisms) of target site-specificity for the modulation of
estrogenic and antiestrogenic response. The description of a stimulatory pathway
for antiestrogens through an AP-1 ER beta signal transduction pathway (Paech et
al., 1997), although interesting, may not entirely explain the estrogenicity of
antiestrogens. The model must encompass the sum of pharmacological consequences
of signal transduction through ER alpha and ER beta with the simultaneous
competition from endogenous estrogens at both sites. This is complicated because
estradiol is an antagonist at ER beta through AP-1 sites (Paech et al., 1997), so
this is clearly not the pathway for estrogen-induced bone maintenance in women.
Estrogen is stimulatory through ER alpha, but antiestrogens are usually partial
agonists and may either block or stimulate genes. However, we suggest that the ER
alpha stimulatory pathway could be amplified through selective increases in
coactivators. The principle is illustrated with the MDA-MB-231 cells stably
transfected with the cDNAs for the wild-type and the amino acid 351 mutan
PMID- 9647866
TI - Signal transduction and signal modulation by cell adhesion receptors: the role of
integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins.
PMID- 9647867
TI - International Union of Pharmacology. XVIII. Nomenclature of receptors for
vasoactive intestinal peptide and pituitary adenylate cyclase-activating
polypeptide.
PMID- 9647868
TI - International Union of Pharmacology. XIX. The IUPHAR receptor code: a proposal
for an alphanumeric classification system.
PMID- 9647869
TI - International Union of Pharmacology. XVII. Classification of muscarinic
acetylcholine receptors.
PMID- 9647870
TI - International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA
receptors: classification on the basis of subunit structure and receptor
function.
PMID- 9647871
TI - Retinoid metabolism in the skin.
PMID- 9647872
TI - The effects of self-administering emergency contraception.
AB - BACKGROUND: Emergency postcoital contraception prevents pregnancy, but it must be
prescribed by a doctor and taken within 72 hours of intercourse. It has been
proposed that emergency contraception be made available without a prescription.
We undertook a study to learn how women might behave if given a supply of
emergency contraceptive pills to keep at home. METHODS: We assigned 553 women to
be given a replaceable supply of hormonal emergency contraceptive pills to take
home (the treatment group) and 530 women to use emergency contraception obtained
by visiting a doctor (the control group). The frequency of use of emergency
contraception, the use of other contraceptives, and the incidence of unwanted
pregnancy were determined in both groups of women one year later. RESULTS: The
results for 549 women in the treatment group and 522 women in the control group
were available for analysis. Three hundred seventy-nine of the women in the
treatment group (69 percent) and 326 of the women in the control group (62
percent) contributed detailed information at follow-up. One hundred eighty of the
women in the treatment group (47 percent) used emergency contraception at least
once. Among those who returned the study questionnaire, 98 percent used emergency
contraception correctly. There were no serious adverse effects. Eighty-seven
women in the control group (27 percent) used emergency contraception at least
once (P<0.001 for the comparison with the treatment group). The women in the
treatment group were not more likely to use emergency contraception repeatedly.
Their use of other methods of contraception was no different from that of the
women in the control group. There were 18 unintended pregnancies in the treatment
group and 25 in the control group (relative risk, 0.7; 95 percent confidence
interval, 0.4 to 1.2). CONCLUSIONS: Making emergency contraception more easily
obtainable does no harm and may reduce the rate of unwanted pregnancies.
PMID- 9647873
TI - Prevention of a first stroke by transfusions in children with sickle cell anemia
and abnormal results on transcranial Doppler ultrasonography.
AB - BACKGROUND: Blood transfusions prevent recurrent stroke in children with sickle
cell anemia, but the value of transfusions in preventing a first stroke is
unknown. We used transcranial Doppler ultrasonography to identify children with
sickle cell anemia who were at high risk for stroke and then randomly assigned
them to receive standard care or transfusions to prevent a first stroke. METHODS:
To enter the study, children with sickle cell anemia and no history of stroke had
to have undergone two transcranial Doppler studies that showed that the time
averaged mean blood-flow velocity in the internal carotid or middle cerebral
artery was 200 cm per second or higher. The patients were randomly assigned to
receive standard care or transfusions to reduce the hemoglobin S concentration to
less than 30 percent of the total hemoglobin concentration. The incidence of
stroke (cerebral infarction or intracranial hemorrhage) was compared between the
two groups. RESULTS: A total of 130 children (mean [+/-SD] age, 8.3+/-3.3 years)
were enrolled; 63 were randomly assigned to receive transfusions and 67 to
receive standard care. At base line, the transfusion group had a slightly lower
mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P=0.001) and
hematocrit (20.4 vs. 21.7 percent, P=0.002). Ten patients dropped out of the
transfusion group, and two patients crossed over from the standard-care group to
the transfusion group. There were 10 cerebral infarctions and 1 intracerebral
hematoma in the standard-care group, as compared with 1 infarction in the
transfusion group -- a 92 percent difference in the risk of stroke (P<0.001).
This result led to the early termination of the trial. CONCLUSIONS: Transfusion
greatly reduces the risk of a first stroke in children with sickle cell anemia
who have abnormal results on transcranial Doppler ultrasonography.
PMID- 9647874
TI - Effects of diet and exercise in men and postmenopausal women with low levels of
HDL cholesterol and high levels of LDL cholesterol.
AB - BACKGROUND: Guidelines established by the National Cholesterol Education Program
(NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein
levels. Little is known, however, about the effects of exercise or the NCEP diet,
which is moderately low in fat and cholesterol, in persons with lipoprotein
levels that place them at high risk for coronary heart disease. METHODS: We
studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64
years of age, and 197 men, 30 through 64 years of age, who had low high-density
lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or
=44 mg per deciliter in men) and moderately elevated levels of low-density
lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in
women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects
were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus
exercise, or to a control group, which received no intervention. RESULTS: Dietary
intake of fat and cholesterol decreased during the one-year study (P<0.001), as
did body weight, in women and men in either the diet group or the diet-plus
exercise group, as compared with the controls (P<0.001) and the exercise group
(P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL
cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did
not differ significantly among the treatment groups, for subjects of either sex.
The serum level of LDL cholesterol was significantly reduced among women (a
decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg
per deciliter) in the diet-plus-exercise group, as compared with the control
group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a
decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL
cholesterol in men in the diet-plus-exercise group was also significant as
compared with that among the men in the exercise group (3.6+/-18.8 mg per
deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not
significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the
men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the
controls. CONCLUSIONS: The NCEP Step 2 diet failed to lower LDL cholesterol
levels in men or women with high-risk lipoprotein levels who did not engage in
aerobic exercise. This finding highlights the importance of physical activity in
the treatment of elevated LDL cholesterol levels.
PMID- 9647875
TI - Chemotherapy alone compared with chemotherapy plus radiotherapy for localized
intermediate- and high-grade non-Hodgkin's lymphoma.
AB - BACKGROUND: Patients with clinically localized, intermediate- or high-grade non
Hodgkin's lymphoma usually receive initial treatment with a doxorubicin
containing regimen such as cyclophosphamide, doxorubicin, vincristine, and
prednisone (CHOP). Pilot studies suggest that eight cycles of CHOP alone or three
cycles of CHOP followed by involved-field radiotherapy are effective in such
patients. METHODS: We compared these two approaches in a prospective, randomized,
multi-institutional study. The end points were progression-free survival, overall
survival, and life-threatening or fatal toxic effects. Two hundred eligible
patients were randomly assigned to receive CHOP plus radiotherapy, and 201
received CHOP alone. RESULTS: Patients treated with three cycles of CHOP plus
radiotherapy had significantly better progression-free survival (P=0.03) and
overall survival (P=0.02) than patients treated with CHOP alone. The five-year
estimates of progression-free survival for patients receiving CHOP plus
radiotherapy and for patients receiving CHOP alone were 77 percent and 64
percent, respectively. The five-year estimates of overall survival for patients
receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82
percent and 72 percent, respectively. The adverse effects included one death in
each treatment group. Life-threatening toxic effects of any type were seen in 61
of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients
treated with CHOP alone (P=0.06). The left ventricular function was decreased in
seven patients who received CHOP alone, whereas no cardiac events were recorded
in the group receiving CHOP plus radiotherapy (P=0.02). CONCLUSIONS: Three cycles
of CHOP followed by involved-field radiotherapy are superior to eight cycles of
CHOP alone for the treatment of localized intermediate- and high-grade non
Hodgkin's lymphoma.
PMID- 9647876
TI - Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing
Cushing's syndrome.
PMID- 9647877
TI - Images in clinical medicine. Budding of human immunodeficiency virus.
PMID- 9647878
TI - Acute human immunodeficiency virus type 1 infection.
PMID- 9647879
TI - Self-administered emergency contraception--a second chance.
PMID- 9647880
TI - Sickle cell disease--new treatments, new questions.
PMID- 9647881
TI - Chemoradiotherapy for localized non-Hodgkin's lymphoma.
PMID- 9647882
TI - Environmental health, risk assessment, and democracy.
PMID- 9647883
TI - Protective role of stress genes.
PMID- 9647884
TI - Vapor recovery systems can reduce risks from MTBE.
PMID- 9647885
TI - Endocrine disruptors and testis development.
PMID- 9647887
TI - Loud--but not yet clear.
PMID- 9647886
TI - The first synthetic estrogen.
PMID- 9647888
TI - Studies shed light on sunscreen efficacy.
PMID- 9647889
TI - Researchers ready rapid Pfiesteria tests.
PMID- 9647890
TI - NIEHS seeks data on multiple chemical sensitivity.
PMID- 9647891
TI - Agreement on pork problems.
PMID- 9647892
TI - New approaches for detecting thresholds of human nephrotoxicity using cadmium as
an example.
AB - Damage to the kidneys is one of the primary toxic actions of metals. Nephrotoxic
substances not only cause renal disease directly, but they can also destroy renal
reserve capacity, potentially placing those people with additional risk factors,
such as diabetes, hypertension, cardiovascular disease, and genetic
predispositions, at greater risk. To detect nephrotoxicity in people at a stage
where intervention can be effective, sensitive methods are needed. One of the
major advantages of using sensitive biomarkers of renal damage is that people who
may be particularly susceptible to renal damage can be identified early, at a
reversible stage of damage, and the progression to end-stage renal disease may be
halted or delayed. Various categories of tests can be used to detect effects of
nephrotoxic substances on the kidney. Through the use of biomarkers of damage to
various parts of the nephron, U.S. and European studies have both shown a similar
pattern of damage among men occupationally exposed to cadmium. These studies
indicate various thresholds of renal effects, which researchers suggest represent
a cascade of progressively severe damage to the kidney. Research into new
biomarkers of damage caused by exposure to nephrotoxic substances centers around
mechanisms of cell death, including necrosis and apoptosis; mechanisms of cell
growth, regeneration, and proliferation, including factors that control cell
cycle, influence gene expression, and modulate nucleic acid synthesis; and
genetic factors that increase susceptibility to renal disease. Examples of types
of candidate biomarkers include cytokines, lipid mediators, growth factors,
transcription factors and protooncogenes, extracellular matrix components
(collagen, glycoproteins, and proteoglycans), and cell adhesion molecules.
Research into new categories of biomarkers may provide additional insights into
the mechanisms of damage caused by nephrotoxins.
PMID- 9647893
TI - Genetic influences on smoking: candidate genes.
AB - Twin studies consistently indicate important genetic influences on multiple
aspects of smoking behavior, including both initiation and cessation; however,
knowledge regarding the role of specific genes is extremely limited. Habit
forming actions of nicotine appear to be triggered primarily at nicotinic
receptors on the cell bodies of dopaminergic neurons in the mesolimbic "reward"
system of the brain, a region implicated in addiction to other substances
including cocaine, opiates, and alcohol. Important aspects of the dopaminergic
pathway include synthesis of dopamine in dopaminergic neurons, release of
dopamine by presynaptic neurons, receptor activation of postsynaptic neurons,
dopamine re-uptake by presynaptic neurons, and metabolism of released dopamine.
Research examining the role of allelic variation in genes involved in these
functions is being actively pursued with respect to addictive behavior as well as
personality traits and psycho- and neuropathologic conditions and has
implications for smoking research. In addition, genetic differences in nicotinic
receptors or nicotine metabolism might reasonably be hypothesized to play a role
in smoking addiction. A role of dopaminergic or other genes in smoking cessation
is of particular potential importance, as research in this area may lead to the
identification of subgroups of individuals for whom pharmacologic cessation aids
may be most effective.
PMID- 9647894
TI - Forms and prevalence of intersexuality and effects of environmental contaminants
on sexuality in cricket frogs (Acris crepitans).
AB - Cricket frogs (Acris crepitans) from several different sites in Illinois were
collected to assess the effects of environmental contamination on the prevalence
of intersex gonads. Of 341 frogs collected in 1993, 1994, and 1995, 2.7% were
intersex individuals. There was no statistically significant relationship between
the chemical compounds detected and cricket frog intersexuality. However, there
was an association approaching significance (p = 0.07) between the detection of
atrazine and intersex individuals. A comparison of reference sites with sites
that had point polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran
(PCDF) contamination revealed a significant relationship between sex-ratio
reversal and contamination with PCBs and PCDFs. The sex ratio of juvenile frogs
studied from three sites with PCB and PCDF point contamination favored males over
females, which was the opposite of the sex ratio in control ponds (p = 0.0007).
The statistically significant correlation between organochlorine contamination
and sex-ratio reversal suggests PCBs and PCDFs can influence cricket frog sexual
differentiation. The current study suggests that in cricket frogs, sex ratios and
the prevalence of intersex gonads are altered by environmental contamination.
PMID- 9647895
TI - Discovering AIDS.
PMID- 9647896
TI - Does the study of environmental disease determinants call for skepticism or open
mindedness?
PMID- 9647897
TI - The decomposition method.
PMID- 9647898
TI - Constipation and colon cancer.
PMID- 9647899
TI - Cancer among a Michigan cohort exposed to polybrominated biphenyls in 1973.
AB - The long-term health effects of human exposure to polybrominated biphenyls are
not known. In this nested case-control study, we evaluated the association
between site-specific cancer risk and serum polybrominated biphenyl levels among
a Michigan cohort accidentally exposed to polybrominated biphenyls in 1973. The
Michigan Department of Public Health has followed 3,899 people through 1993,
among whom 195 primary cancers were identified in 187 persons. Controls were 696
randomly selected cancer-free individuals who were frequency matched to cases by
sex and age (in 5-year strata). Baseline serum polybrominated biphenyl levels
were measured using standard methods. We found an increasing dose-response
relation for digestive system cancer risk with higher serum polybrominated
biphenyl category [4-20 parts per billion (ppb), 21-50 ppb, and > 50 ppb] after
adjustment for age, family cancer history, cigarette smoking, alcohol drinking,
and baseline serum polychlorinated biphenyl level. Adjusted odds ratios (ORs) for
each category were 8.23 [95% confidence interval (CI) = 1.27-53.3], 12.3 (95% CI
= 0.80-191), and 22.9 (95% CI = 1.34-392), respectively. Univariate analysis for
polybrominated biphenyl level and lymphoma risk also showed a dose-response
relation, with corresponding ORs of 3.24 (95% CI = 0.24-95.9), 20.5 (95% CI =
1.51-608), and 32.6 (95% CI = 3.33-861).
PMID- 9647900
TI - Are female drivers safer? An application of the decomposition method.
AB - Using the decomposition method and national data for the year 1990, we examined
gender and age differences in involvement rates in fatal motor vehicle crashes.
The fatal crash involvement rate per driver is expresses as a multiplicative
function of the crash fatality rate (defined as the proportion of fatal crashes
involved among all crashes involved), crash incidence density (that is, number of
crashes per million person-miles), and exposure prevalence (that is, annual
average miles driven per driver). The fatal crash involvement rate per 10,000
drivers for men was three times that for women (5.3 vs 1.7) and was highest among
teenagers. Of the male-female discrepancy in the fatal crash involvement rates,
51% was attributed to the difference between sexes in crash fatality rates, 41%
to the difference in exposure prevalence, and 8% to the difference in crash
incidence density. Age-related variations in the fatal crash involvement rates
resulted primarily from the differences in crash incidence density. The results
indicate that, despite having lower fatal crash involvement rates, female drivers
do not seem to be safer than their male counterparts when exposure is considered.
The decomposition method is valuable as both a conceptual framework and an
exploratory tool for understanding the contributing factors related to cause
specific injury mortality and the differences in death rates among populations.
PMID- 9647901
TI - Constipation, laxative use, and colon cancer among middle-aged adults.
AB - We examined the associations of colon cancer with constipation and the use of
commercial laxatives in a case-control study among men and women ages 30-62
years. We based this analysis on 424 incident cases of colon cancer, diagnosed in
the Seattle metropolitan area between 1985 and 1989, and 414 random-digit-dial
controls. Frequent constipation during the 10 years before the reference data (2
years before diagnosis), as defined by "feeling constipated to the point of
having to take something," was associated with substantially increased risk of
colon cancer. The adjusted relative risk (RR) was 2.0 [95% confidence interval
(CI) = 1.2-3.6] for constipation 12-51 times per year, and 4.4(95% CI = 2.1-8.9)
for constipation 52 or more times a year. Cumulative lifetime use of commercial
laxatives was also associated with increased risk of colon cancer. When
constipation and commercial laxative use were adjusted for each other, the
association with commercial laxative use disappeared, whereas the association
with constipation remained strong. Although constipation has not consistently
been associated in past studies with a large increase in risk of colon and rectal
cancer combined, these results suggest that frequent constipation may be an
important risk factor for colon cancer among middle-aged adults.
PMID- 9647902
TI - Magnetic fields and breast cancer in Swedish adults residing near high-voltage
power lines.
AB - We conducted a case-control study to test the hypothesis that residential
magnetic field exposures increase the incidence of breast cancer. The study was
based on people who had lived within 300 m of 220- or 400-kV power lines in
Sweden at any time between 1960 and 1985. We identified 699 cases of breast
cancer in women and 9 cases in men. One matched control per female case and eight
per male case were selected at random. Estrogen receptor information was
available for a subset of female cases. We assessed magnetic field exposure
through calculations of the magnetic fields generated by the power lines before
diagnosis. For calculated magnetic field levels > or = 0.2 microtesla (microT)
closest in times before diagnosis, we estimated the relative risk to be 1.0 [95%
confidence interval (CI) = 0.7-1.5] for women and 2.1 (95% CI = 0.3-14.1) for
men. Women younger than 50 years of age at diagnosis had a relative risk of 1.8
(95% CI = 0.7-4.3). For women with estrogen receptor-positive breast cancer, the
relative risk was estimated at 1.6 (95% CI = 0.6-4.1), using the exposure cutoff
point > or = 0.1 microT. Among estrogen receptor-positive women younger than 50
years at diagnosis, the relative risk increased to 7.4 (95% CI = 1.0-178.1).
PMID- 9647903
TI - Magnetic field exposure and neurodegenerative disease mortality among electric
utility workers.
AB - Several recent reports indicate that occupational exposure to electric and
magnetic fields may be associated with increased risk of neurodegenerative
diseases. To address that hypothesis, we analyzed data from a cohort study of
electric utility workers. We examined exposure to magnetic fields, assessed as
duration of work in exposed jobs and through an index of cumulative exposure
based on magnetic field measurements, in relation to mortality from Alzheimer's
disease, Parkinson's disease, and amyotrophic lateral sclerosis, considering both
underlying and all mentioned causes of death. Adjusted mortality rate ratios
based on Poisson regression models indicate no association between magnetic
fields and Parkinson's disease and little support for an association with
Alzheimer's disease mortality. Mortality from amyotrophic lateral sclerosis was
positively associated with duration of work in exposed jobs [rate ratio = 2.0,
95% confidence interval (CI)= 0.7-6.0; and rate ratio = 3.1, 95% CI = 1.0-9.8,
based on underlying cause for 5 - < 20 years and > or = 20 years vs < 5 years,
respectively], as well as with cumulative magnetic field exposure with a > or =
20-year lag (rate ratio = 2.3, 95% CI = 0.8-6.6; and rate ratio = 3.0, 95% CI =
1.0-9.2, for exposure in the middle and upper intervals relative to the lowest
interval, respectively).
PMID- 9647904
TI - Associations between lung function and estimated average exposure to NO2 in eight
areas of Switzerland. The SAPALDIA Team. Swiss Study of Air Pollution and Lung
Diseases in Adults.
AB - In this paper, we present results from the SAPALDIA study (Swiss Study on Air
Pollution and Lung Diseases in Adults) regarding associations between lung
function [forced vital capacity (FVC) and forced expiratory volume in 1 second
(FEV1)], as assessed during the cross-sectional study in 1991, and average levels
of NO2 exposure within the eight study communities. We distinguished average home
outdoor exposure and average personal exposure to NO2 and obtained exposure
estimates by computing regional averages of passive sampler measurements
performed by a random subsample of SAPALDIA participants in 1993. Previous
analyses had revealed associations between average lung function and average air
pollution levels between communities. The present results show that such
associations may also be seen within communities: a 10-micrograms per m3 increase
in average home outdoor and personal exposure to NO2 between zones of residence
of the same community was associated with a change in average FVC by -0.59% [95%
confidence limits (CL) = 0.01, -1.19] and -0.74% (95% CL = -0.07, -1.41),
respectively. These values, however, are smaller than the ones found for the
corresponding associations between study communities: -1.67% (95% CL = -1.01,
2.33) and -2.93% (95% CL = -2.11, -3.75), respectively. The different magnitudes
of these two types of associations might be explained by differences in spatial
variation between various components of air pollution.
PMID- 9647905
TI - Use of toenail fluoride levels as an indicator for the risk of hip and forearm
fractures in women.
AB - The relation between fluoride intake and risk of osteoporotic fractures remains
unclear. The lack of individual measures of long-term fluoride intake has limited
epidemiologic studies. We used toenail fluoride in this study as a measure of
long-term intake to evaluate the relation between fluoride intake and subsequent
risk of hip and distal forearm fractures. Between 1982 and 1984, we collected
toenail clippings from 62,641 women in the Nurses' Health Study who were free
from cancer, heart disease, stroke, and previous hip or forearm fracture. We
identified fracture cases (53 proximal femur and 188 distal forearm) through
subsequent biennial mailed questionnaires and matched controls to cases on year
of birth. The odds ratio of hip fracture among women in the highest quartile of
toenail fluoride [ > 5.50 parts per million (ppm)], compared with those in the
lowest quartile (> 2.00 ppm), was 0.8 (95% confidence interval = 0.2-4.0), with
adjustment for menopausal status, postmenopausal hormone use, caffeine intake,
and alcohol consumption. The corresponding adjusted odds ratio for forearm
fracture was 1.6 (95% confidence interval = 0.8-3.1). Further adjustment for body
mass index, smoking status, and calcium and vitamin D intake did not alter these
results.
PMID- 9647906
TI - Risk factors for fractures in the elderly.
AB - We report the results of a 5-year prospective cohort study of risk factors for
fractures, including drinking fluoridated water, in a cohort of 3,216 men and
women aged 65 years and older. We studied risk factors for hip fracture and
fractures at other locations separately. We found a higher risk of hip fractures
for subjects exposed to fluorine concentrations over 0.11 mg per liter but
without a dose-effect relation (odds ratio (OR) = 3.25 for a concentration of
0.11-0.25 mg per liter; OR = 2.43 for > or = 0.25 mg per liter]. For higher
thresholds (0.7 and 1 mg per liter), however, the OR was less than 1. We found no
association between fluorine and non-hip fractures. Non-hip fractures were
associated with polymedication rather than with specific drug use, whereas
fracture was associated with polymedication and use of anxiolytic and
antidepressive drugs. Subjects drinking spirits every day were more likely to
have hip fractures. Tobacco consumption increased the risk for non-hip fractures.
PMID- 9647907
TI - Mortality of aerospace workers exposed to trichloroethylene.
AB - We measured mortality rates in a cohort of 20,508 aerospace workers who were
followed up over the period 1950-1993. A total of 4,733 workers had occupational
exposure to trichloroethylene. In addition, trichloroethylene was present in some
of the washing and drinking water used at the work site. We developed a job
exposure matrix to classify all jobs by trichloroethylene exposure levels into
four categories ranging from "none" to "high" exposure. We calculated
standardized mortality ratios for the entire cohort and the trichloroethylene
exposed subcohort. In the standardized mortality ratio analyses, we observed a
consistent elevation for nonmalignant respiratory disease, which we attribute
primarily to the higher background rates of respiratory disease in this region.
We also compared trichloroethylene-exposed workers with workers in the "low" and
"none" exposure categories. Mortality rate ratios for nonmalignant respiratory
disease were near or less than 1.00 for trichloroethylene exposure groups. We
observed elevated rare ratios for ovarian cancer among those with peak exposure
at medium and high levels] relative risk (RR) = 2.74; 95% confidence interval
(CI) = 0.84-8.99] and among women with high cumulative exposure (RR = 7.09; 95%
CI = 2.14-23.54). Among those with peak exposures at medium and high levels, we
observed slightly elevated rate ratios for cancers of the kidney (RR = 1.89; 95%
CI = 0.85-4.23), bladder (RR = 1.41; 95% CI = 0.52-3.81), and prostate (RR =
1.47; 95% CI = 0.85-2.55). Our findings do not indicate an association between
trichloroethylene exposure and respiratory cancer, liver cancer, leukemia or
lymphoma, or all cancers combined.
PMID- 9647908
TI - Factoring vs linear modeling in rate estimation: a simulation study of relative
accuracy.
AB - A common strategy for modeling dose-response in epidemiology is to transform
ordered exposures and covariates into sets of dichotomous indicator variables
(that is, to factor the variables). Factoring tends to increase estimation
variance, but it also tends to decrease bias and thus may increase or decrease
total accuracy. We conducted a simulation study to examine the impact of
factoring on the accuracy of rate estimation. Factored and unfactored Poisson
regression models were fit to follow-up study datasets that were randomly
generated from 37,500 population model forms that ranged from subadditive to
supramultiplicative. In the situations we examined, factoring sometimes
substantially improved accuracy relative to fitting the corresponding unfactored
model, sometimes substantially decreased accuracy, and sometimes made little
difference. The difference in accuracy between factored and unfactored models
depended in a complicated fashion on the difference between the true and fitted
model forms, the strength of exposure and covariate effects in the population,
and the study size. It may be difficult in practice to predict when factoring is
increasing or decreasing accuracy. We recommend, therefore, that the strategy of
factoring variables be supplemented with other strategies for modeling dose
response.
PMID- 9647909
TI - Accounting for time-dependent covariates whose levels are influenced by exposure
status.
AB - When measuring the association between an exposure and disease, one must decide
whether to account for confounding or modifying variables whose levels are
altered by the presence of the exposure. For example, to assess the impact of
cessation of unopposed estrogen therapy on the occurrence of endometrial cancer,
a researcher needs to consider the duration of the estrogen therapy, a strong
risk factor for endometrial cancer, as a potential confounder or effect modifier.
Duration of estrogen therapy, however, is itself influenced by the decision to
stop the therapy (the "exposure" of interest). In such a case, two distinct
approaches may be taken, depending upon the question being considered. One may
wish to assess the degree to which the exposure predicts disease incidence, over
and above the additional variable, at some later point in time. In this case, it
is appropriate to consider the value of the other variable (for example,
duration) at that later time. On the other hand, one may also wish to measure the
rate of disease beginning at the time of cessation of the exposure, relative to
the corresponding rate in persons with continuing exposure Here, the most
appropriate analysis considers the level of the confounding variable (for
example, duration) measured only until the time of exposure of interest occurs
(for example, cessation of unopposed estrogen therapy). Examples are given to
illustrate that the specific question being addressed dictates the handling of
covariates of this type.
PMID- 9647910
TI - The case-time-control design: further assumptions and conditions.
AB - The case-time-control design is a strategy that was developed to tackle the
problem of confounding by indication in the nonexperimental assessment of
intended or known effects of drugs. By using subjects as their own controls, the
case-time-control design, under an explicitly defined model, eliminates the
biasing effect of unmeasured confounding factors in the situation where exposure
varies over time. The correct application of this design is based on a specific
model that contains inherent assumptions and imposes certain conditions for the
approach to be valid. In a recent article, Greenland questioned the validity of
the case-time-control design by presenting several "counterexamples." In this
paper, we review the assumptions inherent to the validity of the case-time
control model. We show that the presumed counterexamples are not what they are
claimed to be, simply because they do not conform to the logistic model
explicitly underlying the case-time-control approach. These examples are shown to
arise from an alternative model that includes a confounder by period interaction,
a term expressly avoided in the case-time-control model. When the data from these
examples are modified to satisfy the correct model, the resulting case-time
control estimates of the treatment odds ratio are exactly 2, the true treatment
effect. We clarify the necessity of this assumption in the context of matching in
epidemiology. We also discuss briefly the assumptions of conditional independence
and carryover effects.
PMID- 9647911
TI - Probability model on the use of sentinel animal monitoring for arbovirus.
AB - We specify the relations among the major parameters involved in using sentinel
animals to monitor arbovirus transmission. By using probability models, first we
demonstrate that vector density, infection rate, incubation period of sentinel
animals, the number of sentinel animals used, and blood sampling frequency could
directly affect the observed seroconversion rates and the comparison of these
rates. Second, we evaluate the reliability of using sentinel animals to monitor
arbovirus transmission under various conditions. On the basis of the model, we
propose some measures for enhancing the reliability of using sentinel animals to
monitor arbovirus. Third, we present a formula for estimating the number of
sentinel animals used for a study designed to compare seroconversion rates.
Fourth, we derive a necessary condition for deciding the blood sample frequency
of sentinel animals. Fifth, we develop a formula that could be used to obtain the
vector infection rate by using seroconversion data. Finally, we evaluate the
epidemiology consequences of heterogeneous exposure of human hosts to vectors by
theoretical modeling.
PMID- 9647912
TI - Comparison of mortality from peptic ulcer bleed between patients with or without
peptic ulcer antecedents.
AB - We studied mortality related to peptic ulcer bleed in a well defined cohort of
patients in the month after the episode of peptic ulcer bleed. Our objective was
to assess the contribution of peptic ulcer antecedents and other predictive
factors on the risk of dying. The study cohort comprised 1,020 patients
hospitalized for an episode of peptic ulcer bleed between January 1991 and March
1994 and identified in the General Practice Research Database in the United
Kingdom. Six hundred twenty-three patients had no prior episode of peptic ulcer
disease, and 384 had peptic ulcer antecedents; for 13 patients, information was
not available. Forty-five patients died (mortality rate = 4.4 per 100 person
months; 95% confidence interval = 3.3-5.9) within 1 month of the peptic ulcer
bleed. Patients with no peptic ulcer antecedent faced a greater risk of dying
than patients with antecedents (relative risk = 3.0; 95% confidence interval =
1.2-7.1). Elderly patients, those undergoing surgery, and current users of acid
suppressing drugs or nonsteroidal antiinflammatory drugs all had an increased
mortality risk. Patients presenting with their first-ever episode of peptic ulcer
bleed have a higher case fatality rate than those with previous episodes of
peptic ulcer.
PMID- 9647913
TI - Vitamins in HIV disease progression and vertical transmission.
AB - Human immunodeficiency virus (HIV) infection is a major public health problem
worldwide, but particularly in subsaharan Africa and Asia. Numerous observational
studies report inverse associations between vitamin status, measured
biochemically or as levels of dietary intake, and the risk of disease progression
or vertical transmission. Evidence to support these findings has been obtained
from a few randomized placebo-controlled trials. In this paper, we review studies
that examined the role of vitamins A, B, C, D, and E in HIV disease progression
and transmission, and we discuss the potential mechanisms of action of these
vitamins. Adequate vitamin intake leads to enhancement of epithelial integrity
and systemic immunity and could contribute to improved clinical condition among
HIV-infected subjects and reduce vertical transmission by reducing the risk and
severity of opportunistic infection and reducing viral load in blood. Adequate
vitamin status may also reduce vertical transmission through the intrapartum and
breastfeeding routes by reducing HIV viral load in lower genital secretions and
breast milk, respectively. Vitamin supplements may be one of a few potential
treatments that are inexpensive enough to be made available to HIV-infected
persons in developing countries.
PMID- 9647914
TI - Inventing the AIDS virus hypothesis: an illustration of scientific vs
unscientific induction.
PMID- 9647915
TI - Diesel exhaust and lung cancer.
PMID- 9647916
TI - Paternal dioxin and the sex of children fathered by veterans of Operation Ranch
Hand.
PMID- 9647917
TI - The residential case-specular method to study wire codes, magnetic fields, and
disease.
PMID- 9647918
TI - [Determination of the onset of stroke. Satellite Symposium: "Current Approaches
to the Management of Acute Ischemic Stroke", within the framework of the "6th
European Stroke Conference". Amsterdam, 28 May 1997].
PMID- 9647919
TI - [The Danish concept of acoustic neuroma surgery: is it still current?].
PMID- 9647920
TI - [Role of perimatrix fibroblasts in development of acquired middle ear
cholesteatoma. A hypothesis].
AB - The epithelial pathogenesis of acquired cholesteatoma has been widely accepted,
but clinical and experimental data have not been able to answer questions like:
How does a cholesteatoma start or grow or how is bone resorption of conducted?
From our own experiments and literature a new hypothesis of cholesteatoma origin
and growth is drawn. Three prerequisites are necessary for development: (1) the
unique anatomical situation at the ear-drum (two different epithelial layers
close together); (2) chronic destruction of the submucosal tissue in the middle
ear (infection, inflammation); (3) wound healing (proliferation phase).
Destruction of the submucosal space by middle ear infection and cell necrosis
starts the wound healing cascade. In wound healing generally the connective
tissue fibroblasts and macrophages play a pivotal role. Cytokines of the wound
healing thought to promote the re-epithelization of the mucosal defect and scar
tissue development act upon the intact squamous cell layer of the outer surface
of the ear-drum at the same time. Thereby a proliferation of the undamaged
epithelial layer is induced. Cholesteatoma matrix is always surrounded by a layer
of connective tissue, the perimatrix. Persistence of the inflammation causes
permanent wound healing in the perimatrix, proliferation of the fibroblasts
(granulation tissue) and proliferation of the epithelium (matrix). It is
speculated that by virtue of wound healing cytokines of fibroblasts and
macrophages are the driving forces of cholesteatoma origin, growth and bone
destruction.
PMID- 9647921
TI - [Electron microscopy studies of the human vomeronasal organ].
AB - The vomeronasal organ, or Jacobson's organ, is essential for pheromone detection
and reproductive behavior in most mammals. In humans, it has been described as a
blind diverticulum in the anterior nasal septum, but without a documented
function. The purpose of this study is to describe the fine structure of the
human adult vomeronasal organ in 14 specimens. Our studies showed a duct-like
invagination of the epithelium that was surrounded by numerous exocrine glands
with short ducts. The fine structure of these glands suggested a serous
secretion. In the depth of the invagination, pseudostratified columnar epithelial
cells were seen that had plump processes, kinocilia and microvilli at the apical
cell membrane. Several cell types were seen that differed regarding their
organelles and electron density, with light sensory cells exhibiting
neurofilaments. Underneath the typical basement membrane, numerous myelinated and
unmyelinated axons were present in the very vascular lamina proprion. These
morphological findings are unique in the human body and suggest that a
chemosensory epithelium corresponding to a vomeronasal organ may exist. Its
central connections and the possible functional significance of this tubed organ
for pheromone detection are unknown and need further study.
PMID- 9647922
TI - [A micromanipulator for intraoperative vibratory hearing assessment with an
implantable hearing aid transducer].
AB - First concepts of implantable hearing aids to be coupled to the ossicular chain
are available for patients with combined or sensorineural hearing loss (SNHL). To
ensure that hearing can be improved intraoperative coupling of a test transducer
to the ossicular chain is mandatory for allowing surgical anatomy to be checked
and vibratory hearing tests to be performed. To achieve this, the test transducer
has to be held and positioned securely in situ for some minutes, avoiding risks
for middle or inner ear structures. This is not possible using conventional
surgical instruments. Thus, a micromanipulator to hold the test transducer during
intraoperative hearing tests was developed. This surgical device allows the
surgeon safe, risk-free, and controlled coupling of the test transducer to the
ossicular chain with one axial and three rotational degrees of freedom. With the
aid of a conventional ear retractor (2x2 prongs), the manipulator is fixed at the
patient's ear. In conjunction with a piezoelectric test transducer, the
manipulator was used in nine patients during local anesthesia. The test
transducer is part of an electronic hearing implant (Tubingen implant)
specifically designed for SNHL that may be coupled to a middle ear ossicle or the
perilymph of the cochlea. The micromanipulator was easy to handle. It allowed
accurate positioning of the test transducer in the ear and the desired coupling
of the transducer's probe tip to the ossicular chain during auditory tests.
According to the principles of integrated safety, the intraoperative risk of
ossicular or inner ear injuries caused, for instance, by the patient's head
movement is minimized. The design of the manipulator system is universal, also
allowing its use for other electronic hearing implants or minimal invasive
surgery after minor modifications.
PMID- 9647923
TI - [Frequency specificity of acoustic evoked potentials of early and intermediate
latency with high-pass noise masking].
AB - In contrast to auditory brainstem potentials (ABR), a more apically defined
generation of middle latency evoked potentials (MLR) can be assumed due to the
longer integration time present. To date, the effect of stimulus frequency
spectra on MLR has not been completely known. By using masking with high-pass
filtered white noise in 12 normal-hearing adults, we measured the dependence of
amplitude and latency of ABR and MLR on filter frequency. No differences were
found between the masking effects for ABR and MLR evoked by tone bursts of 0.5
and 2 kHz. The high-pass masking of click stimuli showed a greater influence on
the amplitude and latency of the ABR than on MLR. These different qualities have
to be considered clinically when evaluating the methods and results of hearing
testing with acoustic evoked potentials. Our findings show that MLR evoked by
tone bursts should be used for the frequency selective diagnosis of hearing
thresholds, especially in low-frequency ranges.
PMID- 9647924
TI - [Rhinomanometric studies of thermal modification of nasal ventilation].
AB - Elevation of nasal resistance has been described as an effect of increased air
temperature by different authors. The aim of this study was to evaluate the
effect of high environmental temperature on congestion of the nasal mucosa. In
all, 102 volunteers were studied and included normal controls, heart
rehabilitation patients and high performance sportsmen. Rhinomanometric
examinations were carried out before and after 10 min in a dry Finnish sauna at a
90 degrees C temperature. Computerized active anterior rhinomanometry was used. A
uniform response pattern to the increased temperature could not be observed:
i.e., some individuals had an elevated resistance immediately after the sauna
while resistance was decreased in others. The relationship between the reaction
of the nasal mucosa to body work and temperature is discussed.
PMID- 9647925
TI - [Deafness: the right to silence or the chance to hear with a cochlear implant?
Human images and medicine in the world of the deaf and in the world of the
hearing].
AB - Cochlear implantation has evolved from its experimental state into a safe and
effective therapy for the treatment of profound deafness. Although not applicable
to all patients, it offers an alternative to a life in silence. In particular, in
early detected and treated deafness in childhood inner ear prostheses have
enabled affected persons to be integrated into the world of sound. In addition to
the significant impact that therapy has on the life of the individual, there is a
social and cultural consequence for society. This is epitomized in the criticism
by the deaf community that has resulted in the total rejection of cochlear
implants. A critical analysis reveals different personal images prevailing in the
deaf community. Knowledge of these differences and their relevance is important
for all clinicians involved in counselling a cochlear implant candidate.
PMID- 9647926
TI - [Acoustic rhinometry for evaluating the effectiveness of antihistaminics].
AB - Acoustic rhinometry is a unique non-invasive technique for imaging and measuring
the free cross-sectional area of the main nasal cavity. By so doing, reactions of
the mucosa can be assessed at any selected site in the nose. The goal of this
study was to define the optimal conditions for the utilization of acoustic
rhinometry to determine the ability of an antihistamine to alter the effects of
histamine in the mucous membrane of the nose. In a group of 30 healthy volunteers
subjectively normal nasal breathing, and no history of allergy, rhinometry was
performed to measure the cross-sectional area in the region of the head of the
inferior nasal concha at 0.5, 10 and 15 min after histamine provocation. The
volunteers subsequently received cetirizine as antihistamine. Four hours later,
rhinometry was repeated after administration of histamine via the contralateral
nostril. Findings showed that conchal dilatation measured 10 min after
provocation was statistically less severe in 63.3% of the patients treated with
cetirizine. Compared to pretreatment values, the ventilated cross-sectional area
became 45.6% larger after administration antihistamine. These findings
demonstrated that the nasal swelling measured 10 min after antihistamine
administration was due to the effects of histamine and was not due to tactile or
physical stimuli. The present studies showed that the new measurement technique
is precise and reproducible. These results have also demonstrated that a acoustic
rhinometry permits an objective assessment of drug efficacy while making it
possible to avoid the errors observed in other variable regions of the nose, such
as the nasal isthmus or nasopharynx as well as errors associated with subjective
scoring systems.
PMID- 9647927
TI - [Vascular middle ear structure. Ectopic course of the internal carotid artery].
PMID- 9647928
TI - [Voice signal analysis in laryngeal hyperreactivity].
AB - Increased reactions of the laryngeal mucosal membrane can appear after
acetylcholine (ACH) inhalation. A red mucous membrane, vocal cord edema, mucus
formation, changes in the glottic configuration and (rarely) subglottic edema are
visible to laryngoscopic observations. The influence on various voice parameters
in patients with and without laryngeal hyperreactivity was researched in order to
decide the reliability of voice parameter measurements in clinical practice.
Significant variations of the soft phonation index (SPI), the fundamental
frequency variation (vFo), the noise-to-harmonic ratio (NHR) and the voice
turbulence index (VTI) were examined for their correlations with the observable
features of laryngeal hyperreactivity. A single diagnosis of hyperreactivity with
voice parameter analysis failed in 50% of the patients examined because of
functional voice instability and irregularities seen. Only with both laryngoscopy
for reliable discrimination and voice parameter analysis for quantitative
registration were findings sufficient for assessing laryngeal hyperreactivity.
PMID- 9647929
TI - [Transglandular tumor of the parotid gland. Centroblastic-centrocytic lymphoma].
PMID- 9647930
TI - [Lymphoma of the cerebellopontile angle as etiology of retrochochlear damage.
Case report and review of the literature].
AB - The clinical features of progression sensorineural hearing loss and vertigo in
combination with the radiologic finding of a contrast-enhancing mass within the
inner auditory canal are suggestive of an acoustic neuroma. We report our
findings in a 57-year-old woman with known mixed connective tissue disease who
was presumed to have a neuroma. A large malignant lymphoma of the
cerebellopontine angle presented clinically with a primary acoustic none palsy
and no other central neurological deficits. Both the primary radiological
examinations and the exclusively peripheral nerve palsy failed to indicate
manifestations of a lymphoma. The development of a progressive facial palsy
within 8 weeks of presentation and an atypical occipital headache were uncommon
findings for an acoustic neuroma. Such changes in symptoms despite the occurrence
of cardinal symptoms require further diagnostic measures. Manifestations of a
malignant lymphoma in the cerebellopontine angle are extremely rare. To our
knowledge a case of an intracerebral lymphoma in a patient with Sjogren's
syndrome has never been reported before.
PMID- 9647931
TI - [Tracheal wall cyst. A rare cause of stridor in the adult].
AB - A case of tracheal cyst is described in a 43-year-old man who was admitted with
nonspecific symptoms of an obstruction in the upper respiratory tract. A CT scan
of the thorax showed a solid tumor on the inner tracheal wall. Bronchoscopy
revealed a tumor with a broad base and smooth surface that almost completely
obstructed the trachea. Intraoperatively, the tumor was found to be a cyst and
was successfully removed endoscopically. Tracheal cysts are quite rare and most
of the reported cases have been confined to pediatric patients as a congenital
disease. More frequently, congenital intraluminal cysts of the upper respiratory
tract are found as epiglottic retention cysts and laryngoceles.
PMID- 9647932
TI - [Indications for performing uvulopalatopharyngoplasty and laser-assisted
uvulopalatopharyngoplasty].
PMID- 9647933
TI - Sexual behavior of Flinders Line female rats bred for differential cholinergic
sensitivities.
AB - Flinders Lines are two strains of rats selectively bred for their divergent
physiological responses to cholinergic drug challenges. Flinders Sensitive Line
(FSL) rats are highly sensitive to cholinergic stimulation of various autonomic
and behavioral responses compared to Flinders Resistant Line (FRL) rats. Because
cholinergic innervation contributes to the regulation of female sexual behaviors
in rats, a study was conducted to compare the sexual responses of FSL females to
those of FRL females, as well as to those of Long-Evans (LE) females, a
conventional rat strain. Ovariectomized FSL rats exhibited significantly higher
incidences of lordosis and proceptive behaviors than ovariectomized FRL and LE
rats over a range of estrogen doses (2, 3, 4, 5, or 20 microgram(s)/kg estradiol
benzoate at 48 h before testing) administered in combination with progesterone (1
or 2 mg/kg at 4-6 h before testing). In addition, the muscarinic antagonist
scopolamine inhibited lordosis behavior strongly in FRL females over a range of
doses (0.25, 0.5, 1, 2, or 4 mg/kg), but failed to inhibit lordosis in FSL
females. Results indicate that FSL females are highly sensitive to the behavioral
effects of gonadal steroids and highly insensitive to the effects of a muscarinic
antagonist. The enhanced sexual behavioral responses of FSL females could be a
consequence of their well-established cholinergic hypersensitivity or a
consequence of other undocumented characteristics of FSL females such as
hypersensitivity to ovarian hormones. FSL females could provide a valuable model
for the study of estrogen action at behavioral, cellular, and molecular levels.
PMID- 9647934
TI - Androgen-behavior correlations in hypogonadal men and eugonadal men. II.
Cognitive abilities.
AB - Sex-typed cognitive abilities were assessed in 33 hypogonadal men receiving
testosterone replacement therapy, 10 eugonadal men receiving testosterone in a
male contraceptive clinical trial, and 19 eugonadal men not administered
testosterone. Prior to and following hormone administration, men completed four
tests measuring visuospatial ability, three tests measuring verbal fluency, two
tests measuring perceptual speed, and a measure of verbal memory. Group
differences in testosterone levels were unrelated to performance on most
cognitive measures, including visuospatial ability. Relative to other men,
hypogonadal men were impaired in their verbal fluency and showed improved verbal
fluency following treatment with testosterone. These data suggest that
testosterone may enhance verbal fluency in hypogonadal men and support the
general hypothesis that current levels of testosterone may influence some aspects
of cognitive function.
PMID- 9647935
TI - Estradiol increases female sexual initiation independent of male responsiveness
in rhesus monkeys.
AB - Copulation and female initiation of sexual behavior vary across the ovarian
cycle, suggesting that female hormonal condition influences female sexual
motivation in rhesus monkeys. However, the effects of hormones on female sexual
motivation are difficult to identify because male behavior also varies with
female hormonal condition. During the nonbreeding season, male rhesus monkeys are
sexually unresponsive to females; thus the effects of estradiol treatment on
female sexual motivation can be examined independent of male behavior. This study
administered estradiol to five ovariectomized females living in a large age
graded social group during the nonbreeding season. The behavior of these females
with and without estradiol treatment was compared. Data were collected
concurrently on five intact, noncycling, nonpregnant females. Estradiol treatment
significantly increased sexual initiation by ovariectomized females toward males
without any significant changes in male behavior. Estradiol-treated females also
displayed greater sexual initiation than nonpregnant, intact females. Both
estrogen and progesterone were important predictors of sexual initiation in
females, with progesterone having an inhibitory effect. Endogenous progesterone
levels in females were negatively correlated with male contact behavior,
suggesting that female attractiveness is reduced by progesterone. This study
provides further support for estrogen as the critical steroid increasing female
sexual motivation in primates.
PMID- 9647936
TI - Effects of pregnancy hormones on maternal responsiveness, responsiveness to
estrogen stimulation of maternal behavior, and the lordosis response to estrogen
stimulation.
AB - The aim of the study was to determine whether there is an increase in
responsiveness to estrogen stimulation of maternal behavior and lordosis
responsiveness during pregnancy. Using separate groups of pregnancy-terminated
females, we measured the initial maternal responsiveness of hysterectomized
ovariectomized (HO) females and their responsiveness to estrogen stimulation.
Maternal behavior latencies were studied in females HO on the 8th, 10th, 13th,
16th, or 19th day of pregnancy (8HO-19HO) and in nonpregnant HO (NPHO) females.
Groups were injected sc with estradiol benzoate (EB) in doses ranging from 0 to
200 microgram(s)/kg and tested for maternal behavior (retrieving, crouching, and
licking pups). In addition, we investigated whether there is an increase during
pregnancy (following HO) in lordosis responsiveness to estrogen stimulation.
Lordosis behavior was studied in pregnant HO females (days 8, 16, and 22) and
NPHO females given 0 to 200 microgram(s)/kg EB. There was an increase in maternal
responsiveness in oil-treated HO females starting around midpregnancy. From early
pregnancy on there was also an increase in maternal responsiveness to 20
microgram(s)/kg EB. In late pregnant females (16HO) there was a further increase
with 50 microgram(s)/kg EB. There was no increase in lordosis responsiveness to
EB stimulation during pregnancy; pregnant and nonpregnant HO females had the same
EB threshold for stimulating lordosis behavior. The results of both studies were
related to increases during the latter half of pregnancy in nuclear estrogen
receptor concentrations in the MPOA, an area that mediates estrogen stimulation
of maternal behavior, and the absence of such increases during pregnancy in the
VMH, an area that mediates estrogen stimulation of lordosis behavior.
PMID- 9647937
TI - Site-specific opioid receptor blockade allows prepubertal guinea pigs to display
progesterone-facilitated lordosis.
AB - Ovariectomized (OVX) juvenile guinea pigs (approximately 3 weeks old) rarely
display steroid-induced sexual receptivity. Systemic administration of the opioid
receptor antagonist naloxone enhances the display of progesterone-facilitated
lordosis in prepubertal females, suggesting that endogenous opioids tonically
inhibit the expression of sexual receptivity at this age. This study was designed
to ascertain the neural site(s) at which naloxone injection would stimulate
lordosis in juvenile guinea pigs. Hartley guinea pigs were OVX at 10-11 days of
age and 2-6 days later implanted with bilateral cannulae aimed at the medial
preoptic area/anterior hypothalamus (MPOA/AH), ventrolateral
hypothalamus/ventromedial hypothalamus (VLH/VMH), or mesencephalic central gray
(MCG). At 21-23 days of age, following administration of estradiol benzoate (10
microgram(s)) and progesterone (0.5 mg), naloxone (100 ng/side) or 0.9% saline
was injected through the cannulae and the guinea pigs were tested for the display
of lordosis. The MPOA/AH was the only site at which application of naloxone
reliably elicited lordosis (87% positive response vs 12% for saline). Few females
(< 17%) displayed lordosis following injections of naloxone or saline into the
VLH/VMH or MCG. A second experiment demonstrated that the stimulation of lordosis
following MPOA/AH naloxone application was prevented by prior injection of the
opioid agonist morphine (500 ng/side) at the same site. These data support the
hypothesis that endogenous opioids acting in the MPOA/AH, but not the VLH/VMH or
MCG, tonically inhibit the display of progesterone-facilitated lordosis in
prepubertal guinea pigs.
PMID- 9647938
TI - Fos induced by mating or noncontact sociosexual interaction is colocalized with
androgen receptors in neurons within the forebrain, midbrain, and lumbosacral
spinal cord of male rats.
AB - This study was designed to determine the extent to which Fos immunoreactivity
(induced either by mating or noncontact sociosexual interaction) and androgen
receptor (AR) immunoreactivity are colocalized in brain and spinal cord of male
rats. Some males (Mated) were allowed to mate to ejaculation; others (Social
Controls) were placed with females but physical contact was prevented by a wire
mesh screen; remaining males (Isolated) were placed alone in the test jar for the
duration of the test period. After testing, brains and spinal cords were examined
for AR and Fos immunoreactivity (ir). PG21 anti-AR and anti-c-fos primary
antibodies were visualized by fluorescence microscopy using cyanine-conjugated
and fluorescein-conjugated secondary antibodies. In both brain and spinal cord,
the number of Fos-ir neurons varied according to group: Mated males > Social
Controls > Isolated males. Fos was highly localized in subsets of AR-ir neurons
within the medial preoptic nucleus, bed nucleus of the stria terminalis,
dorsomedial nucleus of the amygdala, and central tegmental field. Fos was also
localized in subsets of AR-ir neurons within the L5, L6, and S1 segments of the
spinal cord. Spinal cord concentrations of AR-ir and Fos-ir neurons were greatest
in Lamina X, and the vast majority of Fos-ir neurons in the dorsal part of Lamina
X were also AR-ir. Thus, in both brain and spinal cord, androgen-sensitive
neurons are active during mating, and transmission of sexually relevant
information from cord to brain is probably accomplished via hormone-sensitive
spinal neurons.
PMID- 9647939
TI - Influence of stimuli from chicks on behavior and concentrations of plasma
prolactin and luteinizing hormone in incubating hens.
AB - Removal of eggs from the nests of incubating birds or substitution of eggs for
chicks disrupts incubation behavior and induces changes in the secretion of
prolactin and luteinizing hormone (LH). The aim of the present study was to
determine how different stimuli, such as physical contact with eggs and tactile,
visual, and/or auditory cues from chicks, interact to control the transition
between incubation and brooding and to induce changes in prolactin and LH plasma
concentrations. Physical contact with chicks, in the presence or absence of eggs,
induced brooding behavior and an immediate fall in plasma prolactin concentration
and a gradual increase in LH concentration. Vocalizations, particularly clucking
and food calls, increased rapidly while incubation and nest attachment
disappeared slowly. No change in plasma prolactin or LH concentration was
observed in incubating hens which could hear and see or only hear chicks. These
incubating hens showed no interest in chicks and continued to incubate
persistently. To conclude, tactile stimuli, alone or in combination with visual
and/or auditory stimuli from newly hatched chicks, are the only cues that induce
the transition from incubation to brooding and the associated decrease in
prolactin secretion and increase in LH secretion.
PMID- 9647940
TI - Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile
dysfunction.
AB - Sildenafil citrate has been shown to be effective in a wide range of patients
with erectile dysfunction and has been approved in the United States for this
indication. The overall clinical safety of oral sildenafil, a potent inhibitor of
phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated
in more than 3700 patients (with a total of 1631 years of exposure worldwide).
Safety and tolerability data were analysed from a series of double-blind, placebo
controlled studies and from 10 open-label extension studies of sildenafil in the
treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil,
1552 placebo; age range 19-87 y) received double-blind treatment over a period of
up to six months' duration, and 2199 received long-term, open-label sildenafil
for up to 1 y. The most commonly reported adverse events (all causes) were
headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and
dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and
mild or moderate in nature. These adverse events reflect the pharmacology of
sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were
reported. The rate of discontinuation due to adverse events (all causes) was
comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In
open-label extension studies, 90% of patients completed long-term sildenafil
treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well
tolerated oral treatment for erectile dysfunction.
PMID- 9647941
TI - Does severity of ischaemic coronary disease correlate with erectile function?
PMID- 9647942
TI - Development of an organ culture experimental system to investigate collagen
synthesis in corpora cavernosa.
AB - An organ culture model of rabbit corpus cavernosum has been developed to
investigate fibrillar collagen synthesis in intact organ. Rabbit peni were
removed en bloc, the corpora cavernosa were dissected, sliced into 5 mm pieces
and incubated in culture media up to 24 h. Tissue viability and metabolic and
functional integrity were assessed by (a) lactate dehydrogenase (LDH) release,
(b) protein synthesis, and (c) ability to respond to exogenously added cytokines.
Explants, maintained for 24 h in organ culture, exhibited minimal LDH release and
maintained functional integrity determined from protein synthesis and ability to
synthesize collagen in response to TGF-beta(1). These data suggest that explants
of rabbit corpus cavernosum in organ culture represent a viable model to
investigate connective tissue protein biosynthesis in vitro.
PMID- 9647943
TI - The impact of marital satisfaction and psychological counselling on the outcome
of ICI-treatment in men with ED.
AB - We investigated the relationship between marital satisfaction and choice of and
compliance with treatment in 195 consecutive men with erectile dysfunction (ED).
Marital satisfaction as measured by means of the Maudsley Marital Questionnaire
(MMQ), was compared between four groups: (1) patients on intracavernous injection
(ICI) treatment after the trial-dose phase (32%); (2) patients dropped out ICI in
the trial-dose phase (12%); (3) patients on other treatment (31%); and (4)
patients following first counselling renounced treatment (25%). Above, in a small
group of 15 patients the effect of ICI treatment in combination with short-term
psychological counselling (ICI + treatment) was assessed. No significant
differences were found in marital satisfaction between the four groups. In the
ICI + treatment group we experienced that providing information about factors
that contribute to erectile function and enabling couples to communicate about
sexual problems were the most important factors to increase efficacy of ICI
treatment.
PMID- 9647944
TI - Engineering analysis of penile hemodynamic and structural-dynamic relationships:
Part III--Clinical considerations of penile hemodynamic and rigidity erectile
responses.
AB - PURPOSE: The extent to which hemodynamic erectile responses predict penile
buckling forces has not previously been analytically investigated. An engineering
study was performed to compare hemodynamic data with penile buckling force
values. METHODS: Dynamic infusion pharmacocavernosometry studies in 21 impotent
patients (age 43, range 24-62 y) were accomplished to obtain information during
penile erection concerning hemodynamic values, penile buckling forces and their
determinants: intracavernosal pressure, erectile tissue mechanical properties and
penile geometry. RESULTS: In the 21 patients, discrepancies existed in several
patients who demonstrated normal hemodynamic values (low flow-to-maintain and
high equilibrium intracavernosal pressures) but elevated cavernosal compliance
values and diminished penile buckling forces. There was poor correlation between
cavernosal compliance and equilibrium intracavernosal pressure (r = -0.36);
better correlation between compliance and expandability (r = -0.72) and best
correlation between dimensionless compliance and the dimensionless product of
expandability with equilibrium pressure (r = -0.88). These data implied that
cavernosal compliance was dependent on multiple factors, not only equilibrium
intracavernosal pressure. CONCLUSIONS: Hemodynamic indices which correlate with
intracavernosal pressure alone do not predict penile buckling forces since the
latter are dependent not only on intracavernosal pressure but also on penile
geometry and erectile tissue properties. The most relevant tissue property in
predicting adequate penile buckling forces is cavernosal expandability. A new
impotence classification system and diagnostic algorithm based on the
determinants of penile rigidity and not exclusively on hemodynamic responses in
proposed.
PMID- 9647945
TI - Malignant priapism as the initial clinical manifestation of metastatic renal cell
carcinoma with invasion of both corpora cavernosum and spongiosum.
PMID- 9647946
TI - 'Treatment mills' under the Federal Trade Commission Act.
AB - This paper is based on a presentation made by the author at the meeting of the
American Urological Association's Society for the Study of Impotence on April 12,
1997. The author addresses the general applicability of the Federal Trade
Commission Act to advertising by so-called impotence 'treatment mills,' focusing
in particular on the Federal Trade Commission's case in the matter of Genetus
Alexandria, Inc. et al.
PMID- 9647947
TI - The application of gene therapy to the treatment of erectile dysfunction.
PMID- 9647948
TI - Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the
Society for the Study of Impotence.
AB - During erection, oxygen tension changes in the corpus cavernosum penis from 25-40
mm Hg in the flaccid state to 90-100 mm Hg in the erect state. The relationship
between corpus cavernosum trabecular structure and erectile function is dependent
on a critical balance of smooth muscle to connective tissue for successful veno
occlusion. In this article, the potential role for transforming growth factor
beta(1) (TGF-beta(1)) and prostaglandin E (PGE) in maintaining a functional
smooth muscle/connective tissue balance are discussed as well as the importance
of oxygen tension in the synthesis of these factors. Correlations between animal
models of disease as well as clinical reports are presented in support of a role
for hypoxemia in penile fibrosis. A case is presented for a biological basis of
nocturnal penile tumescence in the preservation of potency and an overall
hypothesis for the molecular pathology of erectile dysfunction is proposed.
PMID- 9647949
TI - Symposium on Peyronie's disease April 12, 1997.
PMID- 9647950
TI - Advances in the medical therapy of Peyronie's disease: a brief review.
PMID- 9647951
TI - Penile prosthesis implantation in the treatment of Peyronie's disease.
AB - PURPOSE: This study was undertaken to evaluate the results and complications of
penile prosthesis implantation in patients with erectile dysfunction caused by
Peyronie's disease. MATERIALS AND METHODS: Men undergoing surgical intervention
for erectile dysfunction caused by Peyronie's disease at the University of North
Carolina School of Medicine were reviewed. Patients included 30 men aged 29-64
(mean = 49.6) with a duration of Peyronie's disease from 12-72 months (mean =
31.4 months). All men had palpable Peyronie's plague, significant penile
curvature and plaque formation. All patients underwent implantation of AMS 700CX
penile prostheses from 1993 to 1997. RESULTS: Penile straightening was carried
out using modeling in 28 (93%) while plaque incision was necessary in 2 men (7%).
All patients had a resultant straight penis with functional penile implant. There
were no patients who suffered penile prosthesis infection and no mechanical
malfunctions were observed during the follow-up. CONCLUSIONS: Penile prosthesis
implantation with modeling is a safe, simple, effective technique for
straightening penile curvature in patients undergoing implantation of penile
prosthesis for Peyronie's disease. Penile prosthesis implantation is a safe,
effective, low morbidity method for restoring potency in men with male erectile
dysfunction and Peyronie's disease.
PMID- 9647952
TI - Correction of penile curvature and Peyronie's disease: why I prefer the Nesbit
technique.
AB - In Peyronie's disease I found that the complication rate after plaque excision
and dermal grafting to be high and started to use the Nesbit technique for the
correction of penile deformity. Since 1977, the overall results have been
satisfactory in 82% of 359 patients. The results improved when those patients
with an impaired erection were assessed by colour doppler studies and a penile
prosthesis implanted in those with a vasculogenic deficit. Post operative
complications of the Nesbit technique are few and penile shortening was not a
problem.
PMID- 9647953
TI - Symposium on Peyronie's disease Society of Impotence Research meeting at the 1997
American Urological Association meeting.
PMID- 9647954
TI - Clinical trials and human sexuality: basic concepts and problems.
AB - In considering the evaluation of pharmacological agents in the treatment of
sexual dysfunction, four fundamental issues are discussed in this paper: (1) most
pharmacological agents which have been used for this purpose act on
neurotransmitter systems which are not specific to sexual response; (2) even when
a sexually relevant pharmacological effect can be assumed, its effect on sexual
behavior will be modulated by information processing; (3) the first attempts to
evaluate the agent should focus on direct effects on the individual receiving the
drug; and (4) evaluation of the relevance of the direct pharmacological effect on
the well-being of a sexual relationship requires control of the considerable
variance which exists in the capacity for change in sexual relationships.
PMID- 9647955
TI - Clinical trials in sexual dysfunction.
PMID- 9647956
TI - Psychological assessment measures of human sexual functioning in clinical trials.
AB - This current review is intended to provide a brief overview of the major design
and psychometric issues inherent in the development of psychological instruments
to assess human sexual functioning. Particular emphasis has been placed on those
issues which derive from the implementation of psychological tests as outcomes
measures in clinical trials. Cardinal psychometric parameters are identified and
reviewed, as are supplementary measurement criteria. Five specific psychological
instruments are recommended and discussed, and each instrument's design
characteristics, psychometric evaluation, and program of validation is briefly
reviewed and evaluated.
PMID- 9647957
TI - Quality of life assessment in sexual dysfunction trials.
AB - Quality of Life (QOL) is an important outcome dimension in clinical trials of
sexual dysfunction. This brief paper reviews the rationale for inclusion of QOL
measures in clinical trials and considers the use of broad-based or generic
measures of QOL, compared to disease-specific measures. Two disease-specific
measures of QOL associated with erectile dysfunction are presented in detail.
Each of these measures has certain advantages, although neither has been
sufficiently validated to warrant large-scale use in clinical trials. Further
research is needed, particularly on the impact of sexual dysfunction on QOL in
women.
PMID- 9647958
TI - Axial penile rigidity: determinants and relation to hemodynamic parameters.
AB - Erectile dysfunction may be defined in terms of axial penile rigidity, the
physical property that enables the erection to be utilized as a penetration tool
during sexual activity. Erectile dysfunction occurs when inadequate axial penile
rigidity results in buckling of the penile column when subjected to axial
compressive loading situations during vaginal intromission. New multi
disciplinary engineering studies of penile hemodynamic and structural dynamic
relationships are reviewed concerning the determinants of axial penile rigidity.
Axial penile rigidity develops as a continuum during the increases in
intracavernosal pressure and volume changes from the flaccid state and is
influenced by intracavernosal pressure, penile tissue mechanical properties and
penile geometry. Two penile tissue mechanical properties are especially relevant;
cavernosal maximum volume at relatively low intracavernosal pressure, and tunical
distensibility, the relative volume of the fully erect to completely flaccid
pendulous penis. Two penile geometric properties are critical; the penile aspect
ratio, defined as the diameter to length ratio of the pendulous penis, and the
magnitude of the flaccid penile diameter. Clinically measured values of axial
buckling forces in patients undergoing dynamic pharmacocavernosometry strongly
correlated to theoretic-based analytic derived magnitudes of axial penile
rigidity based on these above pressure, tissue and geometric determinants. Since
axial penile rigidity is not exclusively dependent upon intracavernosal pressure,
patients with normal erectile hemodynamics may be erroneously labelled as having
psychogenic dysfunction where their true pathophysiology may be related to
abnormal penile tissue properties and/or penile geometric factors. Similarly,
some patients may claim sufficient rigidity for penetration, but have abnormal
hemodynamic erectile function studies. They may have uniquely advantageous tissue
mechanical and/or geometric properties. More research is needed concerning axial
penile rigidity, a most influential factor determining functional erectile
quality, erectile potency and successful coitus.
PMID- 9647959
TI - Neural and pharmacological determinants of erection.
AB - An integrative analysis of the determinants of erection will reveal that almost
all the common actions of smooth muscle and endothelial cells found in normal
vascular biology (NVB), and some neural mechanisms, have roles in supporting
erectile function. Many of these cellular mechanisms have been harnessed to
create drugs that are or will be used to treat erectile dysfunction. Without
standard diagnostic or therapeutic methods, or classifications, it is difficult
to compare drugs, and difficult to target the specific deficiencies causing
erectile dysfunction. A classification is suggested here that hinges on the
identification of two main characteristics. Firstly, there is a fundamental
difference between initiating an erection (initiators) and facilitating or
enhancing an erection already initiated by other processes (conditioners), and
secondly, there are different implications for adverse effects and drug delivery
that arise from targeting central nervous system or peripheral systemic
processes. These properties suggest a classification of treatments based on a two
by-two matrix. Within each class drugs will be more equivalent enabling better
comparisons and more standardized evaluative strategies. By observing the
characteristics of patients benefiting from drugs of an identified class it may
be possible to develop a physiologically based classification of diagnoses. There
may be logical combinations of drugs that will be assembled in clinical practice,
taking suitable agents from one of two or more classes. No single mechanism will
stand out as overwhelming and no single drug will treat all erectile dysfunction.
PMID- 9647960
TI - Central control and inhibitory mechanisms in male sexual response.
AB - At this present time there is a serious gap in our understanding of how
psychological difficulties result in specific sexual dysfunction. In this paper,
a theoretical model of sexual response is proposed which involves the parallel
existence of excitatory and inhibitory mechanisms in the central nervous system.
Evidence for both specifically sexual and non-specific inhibitory mechanisms are
discussed; at this stage either or both may be relevant to the model. It is
postulated that the propensity for neurophysiological inhibition of sexual
response varies across individuals; in the majority of cases it is assumed that
this mechanism has adaptive value. However, in those individuals for whom the
propensity is lacking, high risk sexual behavior may be more likely. In contrast,
those individuals with high propensity for central inhibition may be more
vulnerable to sexual dysfunction. If valid, this model opens a new research
agenda for both male sexual dysfunction and high risk sexual behavior.
PMID- 9647961
TI - A psychophysiological approach to assessing premature ejaculation.
AB - A hierarchical psychophysiological model is described that provides a working
framework for clinicians interested in addressing issues related to premature
ejaculation (PE). Within this framework, psychophysiological laboratory analysis,
used in conjunction with conventional self-report measures, has potential to
contribute both to the measurement and understanding of premature ejaculation and
to the assessment of treatment procedures aimed at alleviating PE.
PMID- 9647962
TI - Definitions and classification of male sexual dysfunction.
AB - The definitions and classifications of male sexual dysfunction as described by
the diagnostic and statistical manual of the American Psychiatric Association are
reviewed. The absence of clear operational criteria for these diagnoses and the
varying definitions used by current investigators are highlighted.
PMID- 9647963
TI - Sexual function assessment in the male: physiological and self-report measures.
AB - Sexual arousal in the male involves a complex interaction of physiological and
subjective processes. In recent years, a number of physiological and self-report
methods have been described for assessing sexual function in healthy and
dysfunctional males. Physiological methods include the Rigiscan, volumetric and
circumferential plethysmography, and the erectiometer. Despite their widespread
use, each of these approaches has significant limitations in assessing male
sexual function. Recent self-report measures include the International Index of
Erectile Function (IIEF), Brief Male Sexual Function Inventory (BMSFI), and
Center for Marital and Sexual Health Questionnaire (CMSH-SFQ). A structured
interview for sexual function assessment has also been described (Derogatis
Interview for Sexual Functioning--DISF-SR), in addition to daily diary and event
log methods. The relative strengths and weaknesses of each of these approaches
are reviewed.
PMID- 9647964
TI - Evidence based assessment of erectile dysfunction.
AB - Do we need impotence testing? Yes, it is the clinician's obligation to establish
the etiology of impotence: end organ vascular failure vs neurologic dysfunction
vs psychosexual dysfunction, classify the severity of that dysfunction, and
select a therapy that is not only acceptable to the patient but also addresses
his pathology. The most commonly utilized diagnostic tests for erectile
dysfunction are outlined in this monograph. Nocturnal erections are evaluated by
tests commonly known as nocturnal penile tumescence (NPT) studies. NPT has been
measured by each of the following methods: stamp test, Snap Gauges, strain
gauges, NPTR (Rigiscan, Osbon Medical Systems), and sleep lab NPTR. Normal
Nocturnal Penile Tumescence and Rigidity (NPTR) depends on both the integrity of
the corticospinal efferents to the penis and vascular responsiveness of the
penile tissues to those nerve signals. When nocturnal erections are of
appropriate duration and strength the central and peripheral neuroeffectors and
intra-corporal regulators of penile hemodynamics are intact. Unfortunately,
abnormal NPTR is of little value in determining the etiology or classifying the
severity of vascular impotence; the most prevalent kind of end organ failure. The
sacral reflex arc of erection consists of somatosensory afferents via the dorsal
and pudendal nerves and autonomic efferents via the pelvic and cavernous nerves.
These afferents have been measured indirectly by somatosensory evoked potentials
(SSEP) and bulbocavernosus reflex latency (BCR). Penile EMG's have recently been
recorded, corporal cavernosal smooth muscle electrical activity: CC-EMG. This
technology is far from standardized; computer-assisted interpretations of penile
electrical potentials may eventually differentiate afferent nerve pathologies so
long inferred in: diabetes, spinal cord injury and following radical pelvic
surgery. Numerous diagnostic tests have been employed to evaluate penile
hemodynamics: penile plethysmography, penile blood pressures, penile brachial
index, selective internal pudendal pharmacoangiography, Doppler sonography,
dynamic infusion cavernosometry/cavernosography, nuclear washout radiography, and
color duplex Doppler ultrasound. Insufficient corporal veno-occlusion is
implicated in up to 50% of patients. The diagnosis and demonstration of venous
leakage requires complete smooth muscle relaxation. Veno-occlusive dysfunction is
associated with poorly sustained erections; this pathology has traditionally been
evaluated with Dynamic Infusion Cavernosometry and Cavernosography. DICC is an
invasive test, and is now primarily reserved for patients considering the option
of vascular reconstructive procedure. Pharmacotesting consists of intracavernous
injection and visual rating of the subsequent erection; the test is the most
commonly used office procedure for diagnosing erectile dysfunction. It is simple,
minimally invasive, and performed without monitoring equipment. Hemodynamic
investigations suggest that a positive injection test is associated with normal
veno-occlusion, but not necessarily with normal arterial function. When the
penile response to pharmacotesting is suboptimal or equivocal, diagnostic testing
with duplex Doppler assessment should be performed. The penile blood flow study
(PBFS) provides an objective, minimally invasive evaluation of a
suboptimal/equivocal erectile response.
PMID- 9647965
TI - Evidence based assessment of rapid ejaculation.
AB - This manuscript reviews the clinical and scientific methods utilized to assess
treatment outcome in rapid ejaculation. The current methods and measures are
critically evaluated and suggestions for future research efforts are included.
PMID- 9647966
TI - The role of androgens and the menopause in the female sexual response.
AB - There is increasing awareness that many women experience symptoms of androgen
deficiency after either natural or surgical menopause. The predominant complaint
of affected women is less sexual desire. Many women experiencing the clinical
symptoms of androgen deficiency and low free testosterone levels respond well to
testosterone replacement therapy. However, some women also have additional psycho
social issues complicating their symptomatology and these must be addressed
either before or concurrently with androgen replacement.
PMID- 9647967
TI - Vasculogenic female sexual dysfunction: vaginal engorgement and clitoral erectile
insufficiency syndromes.
AB - The first phase of the female sexual response, associated with neurotransmitter
mediated vascular smooth muscle relaxation, results in increased vaginal
lubrication, wall engorgement and luminal diameter as well as increased clitoral
length and diameter. Specific physiologic impairments of vasculogenic female
sexual dysfunction include vaginal engorgement and clitoral erectile
insufficiency syndromes. These syndromes exist when during sexual stimulation
abnormal arterial circulation into the vagina or clitoris, usually from
atherosclerotic vascular disease, interferes with normal vascular physiologic
processes. Clinical symptoms may include delayed vaginal engorgement, diminished
vaginal lubrication, pain or discomfort with intercourse, diminished vaginal
sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished
clitoral orgasm. An animal model of this syndrome, with significant physiologic
responses between the control and the atherosclerotic pelvic nerve stimulated
hemodynamic responses, is discussed. Non-atherosclerotic, traumatic vascular
disease of the ilio-hypogastric-pudendal arterial bed from pelvic fractures or
blunt perineal trauma may also result in diminished vaginal/clitoral arterial
blood flow following sexual stimulation. Diagnostic studies assessing the
hemodynamic integrity of the ilio-hypogastric-pudendal arterial bed to the vagina
and clitoris and new oral/topical pharmacologic strategies for enhancing
vaginal/clitoral blood flow in patients with vasculogenic female sexual
dysfunction are discussed. There is a growing body of evidence that women with
sexual dysfunction will commonly have physiologic abnormalities, such as
vasculogenic female sexual dysfunction, contributing to their overall sexual
health problems.
PMID- 9647969
TI - Psychophysiological models of female sexual response.
AB - Psychophysiology provides a methodology and a model for evaluating physiological
and psychological (cognitive-affective) components of sexuality in a relatively
controlled laboratory setting. Laboratory responses can then be correlated with
key sexual or nonsexual self-reported behaviors, thoughts and feelings occurring
in the person's daily environment. Given the fact that human sexual response is
the result of a complex interaction of psychosocial and physiological factors, a
psychophysiological model provides one valuable inroad to exploring and analyzing
sexual response patterns. The following comments briefly evaluate the current
status of the use of this model as it applies to female sexual response.
PMID- 9647968
TI - Ovarian hormones and vaginal blood flow: using laser Doppler velocimetry to
measure effects in a clinical trial of post-menopausal women.
AB - OBJECTIVES: To describe the use of laser Doppler velocimetry for measurement of
vaginal blood flow and report the effects of estrogen compared with estrogen
androgen treatment in post-menopausal women. DESIGN: Literature review of pelvic
blood flow studies and sexual function. Findings from a prospective, randomized,
parallel study. SETTING: Normal human volunteers in an academic research
environment. INTERVENTIONS: Laser Doppler measurements of vaginal blood flow were
compared before and after the administration of oral esterified estrogens or
esterified estrogens plus methyltestosterone for four and eight weeks of daily
drug administration. MAIN OUTCOME MEASURES: Vaginal blood flow velocities.
RESULTS: Laser Doppler velocimetry proved readily adaptable for measurement of
vaginal blood flow. Although esterified estrogens plus methyltestosterone showed
greater effects on blood flow than esterified estrogens alone, the results were
not statistically significant. CONCLUSIONS: Vaginal blood flow is an objective
measure of sexual function which can be determined with laser Doppler
velocimetry. The vasodilator effects of esterified estrogens and esterified
estrogens with methyltestosterone are similar.
PMID- 9647970
TI - Definition and classification of female sexual disorders.
AB - The diagnosis and classification of female sexual disorders has undergone
significant changes over the last fifty years as a function of changing societal
expectations for female sexual conduct, available knowledge about sexual
psychophysiology and actual clinical practice. Currently, female sexual disorders
are conceptualized as disturbances in desire, arousal, or orgasm as well as
sexual pain disorders which include dyspareunia and vaginismus. The lack of
objective, empirically-grounded criteria for diagnosis as well as the comorbidity
of female sexual disorders contributes to the lack of reliability in the
diagnosis of female sexual complaints. At the present time, hypoactive sexual
desire disorder is the most commonly diagnosed female sexual disorder followed by
female orgasmic disorder. Nevertheless, the major clinical complaints among women
center on their dissatisfaction with such non-genital behaviors as affection,
communication, and non-genital touching as well as issues of attraction and
passion. These factors should be assessed as well as genital response for greater
validity in evaluating female sexual disorders in both research and clinical
practice.
PMID- 9647971
TI - Physiological measures of vaginal vasocongestion.
AB - This paper reviews reliability, specificity, and practical applicability of the
two most promising and widely used methods for measuring blood flow within the
vagina: the oxygenation-temperature method and vaginal photoplethysmography. It
was concluded that the oxygenation-temperature method and vaginal pulse amplitude
as measured by the photoplethysmograph are both specific indicators of
physiological sexual arousal. Although vaginal pulse amplitude seems to be the
method of choice for measuring vaginal vasocongestion up to orgasm, and the
oxygenation-temperature method for measuring orgasm, these measures should not be
used in isolation. It is argued that women's sexual function should be evaluated
using vaginal vasocongestion measures in conjunction with subjective indices.
Finally, the field is in need of studies comparing physiological and subjective
sexual responses in clinical and non-clinical groups.
PMID- 9647972
TI - Psychological assessment measures of female sexual functioning in clinical
trials.
AB - The focus of this review is on the psychological measurement of female sexual
functioning, and the particular requirements associated with the implementation
of psychological instruments as outcomes measures in clinical trials. In addition
to the general psychometric criteria which must be met by all psychological
measures, unique confounds associated with the nosology of female sexual
dysfunctions are also discussed. A rationale for the utilization of measurement
models closely tied to the sexual response cycle is articulated, and five
specific test instruments which reflect this rationale to varying degrees are
reviewed as to their psychometric characteristics, and validity as potential
outcomes measures in clinical trials.
PMID- 9647973
TI - The clinical evaluation of dyspareunia.
AB - Strictly defined, dyspareunia means 'pain with intercourse'. The psychiatric DSM
IV subdivides and expands this definition and introduces psychogenic factors into
the differential diagnosis. This allows development of a biogenic-psychogenic
model, whereby organic or psychological factors can be present separately or in
combination, within the disorder. Sexual dysfunctions are estimated to be present
in 19-63% of women, with dyspareunia the primary complaint in 8-48%. The clinical
evaluation of dyspareunia should include a thorough history and meticulous
gynecologic examination. Laboratory or imaging studies should be ordered as
warranted by suggestive history or exam findings. Identified causes should be
treated and counseling considered. Three clinical dilemmas remain. Firstly, lack
of standardization of exam findings; secondly discrepancy between objective
physical findings and subjective patient complaints; and thirdly paucity of
therapeutic options for patients, especially those with an unclear diagnosis. An
integrated psychogenic-biogenic model should be developed and implemented for
effective diagnosis and treatment of dyspareunia.
PMID- 9647974
TI - Issues and priorities in the development of drug treatments for female sexual
dysfunction.
PMID- 9647975
TI - Sexual functioning in the spinal cord injured.
AB - This article reviews current knowledge about the impact of SCI on male and female
sexual responses including erectile function, lubrication ejaculation and orgasm.
The ability to achieve erection, lubrication and ejaculation can be described
based upon the degree and type of neurologic injury affecting the sacral spinal
segments. The ability of SCI individuals to achieve orgasm has not been found to
be based upon the type of degree of neurologic injury. The implications of these
findings to increase our understanding of human sexual neurophysiology is also
discussed.
PMID- 9647976
TI - Psychiatric illness and sexual function.
AB - Impaired sexual function has been noted to occur in various psychiatric
illnesses. In affective disorders, disturbances of libido, erection and orgasm
have been reported. Disordered sexual behavior has also been noted in patients
with schizophrenia and anorexia nervosa. Clinical speculation suggests that
anxiety disorders may also be associated with a higher prevalence of sexual
problems.
PMID- 9647977
TI - Ethical and cultural concerns in sexual function assessment.
AB - The ethical and cultural issues accompanying sex research methods are rarely
discussed. The present remarks briefly examine three previously described ethical
principles--respect for people, beneficence and justice--as they might relate to
sexual dysfunction assessment in clinical trials. Given the fact that sexuality
is a social behavior and the outcome measures are reliant on some form of self
report, there are specific pressures on investigators to conduct research
assessment that respects ethical principles and cultural values. Examples with
respect to screening criteria and participant selection are discussed.
Recommendations include: (a) excluding participants with selected sexual and non
sexual diagnoses, psychosocial behaviors and habits; (b) including proportional
ethnic groups as well as non-heterosexual participants; and (c) considering the
couple, rather than just an individual, as study subjects who each require
medical and psychosocial screening, assessment, and informed consent.
PMID- 9647978
TI - [Acute liver failure].
PMID- 9647979
TI - [Acute pancreatitis after shock, ischemia, reperfusion, trauma and infection].
PMID- 9647980
TI - [Acute heart failure].
PMID- 9647981
TI - [Acute septic cardiomyopathy].
PMID- 9647982
TI - [Disordered hemostasis related to sepsis and SIRS].
PMID- 9647983
TI - [Acute encephalopathy, polyneuropathy and myopathy in the critically ill
patient].
PMID- 9647984
TI - [Multiple organ dysfunction syndrome and multiple organ failure. Diagnosis,
prognosis and therapeutic concepts].
PMID- 9647985
TI - [Scores for multiple organ dysfunction and multiple organ failure].
PMID- 9647986
TI - [Colorectal carcinoma. Prevention and early detection].
PMID- 9647987
TI - [Current therapy of coronary heart disease. Conservative measures].
PMID- 9647990
TI - [Translaryngeal intubation in long-term ventilation].
PMID- 9647992
TI - [Ulcerating skin lesions in terminal renal failure. Successful therapy with
carbon perfusion].
PMID- 9647993
TI - [18-year-old patient with left thoracic pain].
PMID- 9647994
TI - [Acidic blood pH value caused by stress?].
PMID- 9647995
TI - [Dexamethasone in treatment of brain edema and intracranial hemorrhage].
PMID- 9647996
TI - [Iron replacement. Oral or parenteral?].
PMID- 9647997
TI - [APC resistance. Significance--diagnosis--therapeutic consequences].
PMID- 9647998
TI - [Managing advance directives in emergency care].
PMID- 9647999
TI - [Interactions between anticoagulants and cardiovascular drugs].
PMID- 9648000
TI - [6th Munchen AIDS-Days. Azithromycin in HIV-associated opportunistic infections].
PMID- 9648001
TI - [From prevention to therapy of thromboembolic processes: low-molecular heparin in
body-weight adapted dosages].
PMID- 9648002
TI - [Twin transfusion syndrome].
PMID- 9648003
TI - [Role of cervical modifications in threatened premature labor].
AB - Uterine cervical modifications play a central role in preterm labor and are one
of the main indicators for the clinical diagnosis of this syndrome. Modifications
of the cervix are either isolated events "cervical incompetence" or associated
with cervicovaginal infection, which is an important etiological factor.
Furthermore, the extent of cervical modifications in preterm labor is probably
related to the prognosis of preterm delivery. Certain developments in the
treatment of preterm pregnancy have focused on the uterine cervix (e.g. cervical
cerclage, treatment of cervicovaginal infections) and such strategies may
facilitate the prevention of preterm delivery. The information currently
available emphasizes an independent role for the uterine cervix in preterm labor.
As a consequence, it should be realised that even though there is a direct
association between cervical modifications and uterine contractions, management
of preterm labour must not be directed exclusively at the control of uterine
contractions and tocolysis.
PMID- 9648004
TI - [Perinatal hemolytic disease. Part 2: Prevention and management].
AB - There has been a dramatic reduction in the incidence of neonatal mortality due to
fetal hemolytic disease since the introduction of Rhesus prophylaxis. Although
routinely used since 1968, the exact mode of action of anti-D IgGs is still not
fully understood. Notable advances have taken place in the screening and the
management of fetal hemolytic disease. This article describes the antibody
detection in the mother, and the fetal management with ultrasound amniocentesis,
fetal blood sampling and intrauterine transfusions. Finally, the postnatal
management is also considered.
PMID- 9648005
TI - [Female fertility prognosis and diethylstilbestrol. Personal data and review of
the literature].
AB - Diethylstilbestrol (DES) exposure in utero in females is a cause of clear-cell
adenocarcinoma of the cervix and of several anatomical and functional disorders
of the genital tract. DES exposure must be evoked whenever counselling women for
reproductive disorders. In France around 80,000 women have had in utero DES
exposure. The cases of 4 young women who consulted our Reproduction Center for
reproductive disorders illustrate the usual difficulties faced by these patients.
In spite of their difficult past reproductive history (uterine malformations,
repeated miscarriages, ectopic pregnancies) and low fertility rate, all four
women conceived successfully, either after spontaneous or induced ovulation. We
stress the need for adapted psychological and medical care which can lead to
successful childbearing in the vast majority of these high-risk patients.
PMID- 9648006
TI - [Monitoring women on tamoxifen ].
AB - Worldwide, 7 million women are taking tamoxifen for breast cancer. The beneficial
effects of tamoxifen on patient survival have been clearly demonstrated.
Tamoxifen has few adverse effects and severe complications are very uncommon. An
higher risk of endometrial cancer at the 20 mg/d dosage has been discussed and if
it does exist, is minimal (RR x 2 instead of 1.3). Patient monitoring is
basically clinical with an annual examination of the lower limbs and genital
organs and an ophthalmological examination. Further explorations are needed in
cases with specific symptoms, especially metrorrhage. There has been no proof
that systematic endometrial cytology or ultrasound explorations are useful.
PMID- 9648007
TI - [Ultrasonographic signs of chromosome aberrations].
AB - We reviewed the literature on ultrasonographic criteria allowing prenatal
diagnosis of chromosome aberrations, especially the most frequent: trisomy. Signs
vary depending on the term of the ultrasound examination (first trimester
ultrasound is often performed to early and several signs are observed in the
second trimester). During the first trimester, the main criteria is the diagnosis
of nuchal clearness 3 mm. The distance can only be measured with an appropriate
sagittal CRL section by an experienced operator. The ideal term of this
morphology ultrasound is 10 weeks gestation. During the second trimester, there
are many suggestive criteria including non-specific signs: anomalous quantity of
amniotic fluid, short femur, nuchal thickness 6 mm, isolated anomaly of the
umbilical velocimetry, pyelectasy and fetal malformations (mainly cerebral or
abdominal, including ophalocele and diaphragmatic hernia, anomalies, abnormal
heart anatomy, cystic hygroma, facial anomalies and malformations of the members,
often abnormal flexion of the hands).
PMID- 9648008
TI - [Twenty practical questions about prenatal corticosteroid therapy].
AB - Since Liggins and Howie first published their work, numerous studies have shown
that corticosteroids significantly decrease perinatal mortality and morbidity,
without complication for the mothers and child. Corticosteroids should be
prescribed in case of threatening premature birth. Imminent delivery premature
rupture of the membranes and gestationnal age over 34 weeks are not
contraindications to prescription, as corticosteroids can be safely given all in
these circumstances. Theoretically, more than half of premature neonates should
have been treated with corticosteroids. Actually, only 20% or less are currently
treated. The cost-effectiveness ratio of an antenatal corticosteroid policy would
be extremely positive: more than 1,500 prenatal deaths could theoretically be
avoided in France annually and the overall cost of neonatal care would decrease
by 10%.
PMID- 9648009
TI - [Urinary stress incontinence. Comparison of the Raz technique and the Bologna
technique. Analysis of a series of 188 patients].
AB - OBJECTIVE: Our purpose was to evaluate and compare the perioperative morbidity
and the long-term results of the Raz colposuspension and the Bologna operation
for the treatment of stress urinary incontinence in women. STUDY DESIGN: Data of
188 women who underwent either a Bologna operation (group 1) or a Raz
colposuspension (group 2) for the treatment of stress urinary incontinence
between January 1, 1987 and December 1, 1995 were analysed retrospectively
regarding history, preoperative evaluation, associated surgical procedures,
complications and cure and failure rate. POPULATION AND METHODS: 80 patients were
treated with the Bologna operation and 108 with the Raz colposuspension. Patients
with prior anti-incontinence surgery, and patients with a preoperative diagnosis
of urge incontinence were excluded from the study. Success was defined both
subjectively (complete absence of complaint of stress urinary incontinence) and
objectively (no evidence of loss of urine on cough provocation during physical
examination). Survival curves were generated in each group for time to event
data: "time to recurrent stress incontinence" and compared by the logrank test. A
multivariate analysis using a Cox proportional hazards regression model was
performed to indentify possible outcome predictors. RESULTS: The success rate of
group 1 was significantly higher than that of group 2 (p = 0.00001). The median
of success was 51 months in group 1 and 21 months in group 2 (p = 0.00001). The
incidence of intraoperative complications in each group (inadvertent cystostomy,
hemorrhage) did not differ. The multivariate analyses using the Cox regression
model showed that the most highly correlated variable with the surgical cure rate
was the type of surgical anti-incontinence procedure adopted: Bologna or Raz (p =
0.00001) CONCLUSION: In our hands, the Bologna operation has a higher cure rate
than the Raz colposuspension. For us, when treating patients with stress urinary
incontinence by the vaginal route, the Bologna operation is indicated when
sufficient anterior vaginal tissue is available to create vaginal bands.
PMID- 9648010
TI - [Prevention of prematurity in 842 consecutive twin pregnancies].
AB - OBJECTIVE: To evaluate the effects of a specific management in prevention of
prematurity in twin pregnancies. METHOD: The parameters involved in obstetrical
follow-up of twin pregnancies were evaluated in a retrospective study of 842 twin
pregnancies between 1979-1992. RESULTS: Five-hundred-and-fifteen pregnancies were
spontaneous. Two-hundred followed treatment with ovulation induction agents and
127 were due to in vitro fertilization. Early diagnosis of twin pregnancies
allowed preventive measures against prematurity. Management of twin pregnancies
included rest at home and regular clinical examination of the cervix. Monthly
consultations and monthly ultrasounds were performed at hospital. Weekly
consultations were made by midwives at home. Hospitalization was not systematic,
but was necessary in cases of maternal complications. The diagnosis of twin
pregnancy was made before 16 weeks in 82.4% of the cases. The mean gestational
age at delivery was 36.2 weeks. The prematurity rate was 45.96%. The mean weight
of the neonates was 2,376 +/- 533 g for the first twin and 2,297 +/- 547 g for
the second twin. The mean Apgar score at 5 minutes was 9.7 and 9.3, respectively
for the first and the second twin. The perinatal mortality was 39.3 per 1,000.
The main neonatal complications resulted from prematurity. Twins were
hospitalized in the intensive care unit in 20.7 cases. CONCLUSION: The present
study supports early diagnosis of multiple pregnancies with systematic ultrasound
at 11-13 weeks for each pregnancy, information of the patients, rest at home and
regular clinical examination of the cervix.
PMID- 9648011
TI - [Intracystic breast carcinoma. A case report].
AB - Intracystic breast carcinoma is a malignant which develops within breast ducts.
The clinical examination reveals a breast cyst containing a blood fluid which
persists after the puncture. Fine-needle aspiration cytology may be benign. The
endocystic mass is detected well by the ultrasound and US-guided puncture is
possible. Papillary carcinoma is the most frequent histological type.
Conservative prophylactic radiotherapy with surgery can be proposed. Prognosis is
poorer with stromal involvement.
PMID- 9648012
TI - [Ureteral suture by laparoscopy: a new case. Review of the literature].
AB - A wound to the ureter is a possible complication of laparoscopy and is usually
repaired by suture requiring laparotomy. We report a case of a laparoscopic
stitch and review the pertinent literature.
PMID- 9648013
TI - [Prenatal diagnosis of a pancreatic cyst due to Ivemark II syndrome].
AB - We present a case of pancreatic cyst associated with other malformations which
was diagnosed at antenatal ultrasound. Renal, hepatic, and pancreatic dysplasia
as described by Ivemark in 1959 was confirmed by the pathology examination. This
uncommon and lethal syndrome demonstrates autosomic recessive transmission.
Ultrasound evidence of renal, hepatic and pancreatic dysplasia, associated with
femoral abnormalities is suggestive of Meckel's syndrome. Other differential
diagnoses are more easily distinguished (chondrodysplasia, chromosomal or
metabolic abnormalities).
PMID- 9648014
TI - [Thoughts on a case of unrecognized congenital rubella].
AB - We recently observed a case of congenital rubella which had gone unrecognized
despite regular obstetrical care. This case emphasizes the importance of careful
screening for rubella at diagnosis of pregnancy. Minute analysis of the initial
maternal antibody levels is essential to rule out possible contamination during
pregnancy. The problem of interpreting serodiagnostic data is discussed.
PMID- 9648015
TI - [Need for information in obstetrical epidural analgesia].
PMID- 9648016
TI - Is it only rock 'n' roll? The chicken-and-the-egg dilemma.
PMID- 9648017
TI - Fine-needle aspiration of breast masses. A review of its role in diagnosis and
management in adolescent patients.
AB - PURPOSE: To assess the role of fine-needle aspiration biopsy (FNA) in the
evaluation and management of breast masses in adolescents. METHODS: All FNAs
performed on organ masses over a 15-year period on patients age 21 years and
younger were evaluated. Cases were collected from four large university
affiliated teaching hospitals and clinics. Pathology records from the laboratory
information systems were reviewed. Data included clinical information, anatomic
site, and cytologic diagnoses. Surgical follow-up was included when available.
RESULTS: Three hundred and twenty-five FNAs from 302 patients were reviewed. Of
325 aspirates, 59 were breast FNAs (in 51 patients: 4 males and 47 females).
Among all organs, the breast was the most common one aspirated in females. Of the
breast aspirates in females, 49% were diagnosed as fibroadenomas. No cases of
malignant breast disease or phyllodes tumors were encountered. Surgical biopsy
follow-up was available in 23.7% of the patients. Of those masses which were
subsequently surgically biopsied, most were diagnosed as either fibroadenoma (11)
or juvenile fibroadenoma (two). One other case biopsied showed ductal hyperplasia
and adenosis. The majority of the remaining cases were followed up clinically,
since the clinical nature and cytologic features of the lesions were those of
fibrocystic changes or benign cysts. CONCLUSIONS: In the series of FNAs we
examined, breast masses were the most frequent lesions aspirated in adolescent
females, with fibroadenomas being the most common lesion encountered. FNA proved
to be a useful and reliable tool in the evaluation and management of masses
involving the adolescent breast. The majority of breast masses in adolescents are
benign, and lesions can be managed conservatively in this age group. The use of
noninvasive diagnostic procedures such as FNA and ultrasound can reduce the need
for open surgery during breast development.
PMID- 9648018
TI - Changes in self-esteem in black and white girls between the ages of 9 and 14
years. The NHLBI Growth and Health Study.
AB - PURPOSE: We examined changes in self-esteem and feelings of competence with
physical appearance and social acceptance over approximately 5 years in 1166
white and 1213 black girls, aged 9 and 10 years at baseline. METHODS: Maturation
stage and body mass index (BMI) were assessed annually. Biennially girls
completed Harter's Self-Perception Profile for children. Changes were analyzed in
the context of race, sexual maturation, BMI, and household income. Longitudinal
regression models were used to compare trends with age in global self-worth,
physical appearance, and social acceptance. RESULTS: Mean global self-worth
showed little change over ages 9-14 years in blacks (p = 0.09) but decreased in
whites (p < 0.001). Mean physical appearance scores for both races declined
between ages 9 and 14 years (blacks, p < 0.001; whites, p < 0.001). Mean social
acceptance scores increased for both races between ages 9 and 14 years (blacks, p
< 0.001; whites, p < 0.001). For all three scores, these changes differed between
blacks and whites (all three p values, < or = 0.002). Adjustment for maturation
stage, BMI, and household income did not alter the significance or direction of
racial differences in the changes with age in global self-worth and physical
appearance scores. Self-worth, physical appearance, and social acceptance scores
decreased with increasing BMI. Decreases in physical appearance and social
acceptance scores with increasing BMI were smaller in blacks than in whites (p <
0.05). After adjustment for maturation stage and household income, racial
differences in social acceptance scores depended on BMI (p < 0.05) but not on age
(p = 0.008). CONCLUSIONS: This article reports the first data on self-esteem
scores by age for a large population of black girls aged 9 and 14 years and
concludes that self-esteem does not follow the same developmental pattern in
black as in white girls. A reason for black girls' higher and more stable self
worth and their greater satisfaction with their physical appearance compared to
white girls may be racial differences in attitudes toward physical appearance and
obesity.
PMID- 9648019
TI - Self-reported honesty among middle and high school students responding to a
sexual behavior questionnaire.
AB - PURPOSE: To determine self-reported honesty in completing a sexual and other risk
behavior questionnaire among middle and high school students, and to relate
honesty scores to sexual behavior item responses as a method to detect bias in
reporting. METHODS: A self-administered questionnaire measuring overall honesty
(7-point rating scale), sexual honesty (5-category scale), and selected sex
behaviors was used. Urban, predominantly minority middle and high schools (Grades
7-12) were examined, and participants were 3144 male and female students in
middle (mean age = 13.7 +/- 2.0) and high (17.3 +/- 1.6) school health classes.
RESULTS: The majority of students stated that they had been very or completely
honest in responding to items on the questionnaire. Seventy-eight percent of
middle school males (lowest rate), and 94% of high school females (highest rate)
reported honesty. Middle school males were most likely to declare dishonesty
regarding sexual behavior items, overstating their actual behavior (14%), while
middle school girls were most likely to understate (8%) their behavior. Self
reported sexual honesty and reports of behavior were most consistent for
understaters. That is, those subjects who answered that their questionnaire
responses underreported their true sexual behavior did, in fact, report lower
sexual activity on selected survey items. CONCLUSION: Middle and late adolescents
reported high levels of honesty in responding to a sexuality-related
questionnaire. When interpreting such questionnaire data, correction for the
tendency to overstate among middle school males and understate among middle
school females should be considered; conclusions about self-reports of sexual
behavior among young adolescents need to take into account degree of honesty.
However, the presence of some overreported and some underreported behavior does
not invalidate interpretation of the overall survey findings.
PMID- 9648020
TI - The school-linked health center: a promising model of community-based care for
adolescents.
AB - PURPOSE: To examine the nature of the linkages between school-linked health
centers (SLHCs) and schools; the centers' services, staffing, financing, and
other operational details; and the advantages of this model of care. METHOD:
Twenty-one SLHCs completed a written survey on a range of operational issues,
including types of services provided, staffing patterns, budgets, and populations
served in 1995. The researchers conducted on-site interviews with six centers and
telephone interviews with 14 centers to obtain more detailed information.
RESULTS: Although each SLHC has a unique program design, the study identified
characteristics common to all sites. In general, SLHCs provide comprehensive
medical, reproductive health, mental health, and health education services
designed for adolescents. Staffed with a minimum of an administrator, a primary
care provider, a nurse, and an administrative assistant, SLHCs serve students
from more than one school as well as out-of-school youth. SLHCs develop formal
and/or informal linkages with schools to improve outreach and follow-up services.
CONCLUSIONS: The report describes a community-based model of care that is
designed to provide affordable, age-appropriate, confidential, convenient care to
adolescents, a population that traditionally has been very hard to reach. The
SLHCs ability to provide reproductive health care makes it an attractive option
for communities trying to prevent pregnancy and sexually transmitted diseases
among adolescents. To firmly conclude that the SLHC is an effective model for
improving adolescent access to services, more research is needed on adolescents'
use and nonuse of SLHCs and other models of care; the cost of SLHCs compared to
other models of care; and how SLHCs can sustain themselves financially,
particularly in a managed care environment.
PMID- 9648021
TI - Variations in HIV risk behaviors of incarcerated juveniles during a four-year
period: 1989-1992.
AB - OBJECTIVE: To retrospectively monitor over several years change in incarcerated
juveniles' human immunodeficiency virus (HIV) risk behaviors. METHODS: From 1989
to 1992, detainees who volunteered after an HIV class or were referred by a
health care provider were counseled individually and privately by health
educators using a standardized questionnaire and counseling form developed from
an instrument used to counsel prostitutes in Los Angeles, California. RESULTS:
The number counseled each year was 1045, 1745, 2354 and 1428 from 1989 to 1992,
respectively. Those agreeing to HIV testing rose from 72% of total participants
in 1989 to 84% of total participants in 1992. Eight of those youth tested as HIV
positive. Four blind seroprevalence studies during the same time yielded one case
in 1000 for 1988, one case in 1005 for 1989, two cases in 751 in late 1989
(2.7/1000), and one case in 1214 for 1990 (1.25/1000). The number worrying about
AIDS and considering themselves vulnerable to AIDS increased, but protective
behaviors did not. Sexual partners per year were 2.1 regardless of the age of
first sexual activity. Alcohol was associated with an increased number of sexual
partners (2.6/year) and higher rates of sexually transmissible infections (STIs)
and pregnancy. Although 96% of boys and girls were sexually active, only 4% used
a condom consistently during the first 3 years, and only 7% in 1992. Those
reporting having used condoms with the intention to prevent both STIs and
pregnancy had a higher rate of use. Those carrying condoms all the time used
condoms more often. Males having sex with both males and females rarely used
condoms, and 45% had one or more STIs. CONCLUSIONS: Although the rate of HIV
infection remains low in juveniles detained by the County of Los Angeles, their
rates of risky behaviors place them at high risk for HIV acquisition.
PMID- 9648022
TI - Adolescent emotional response to music and its relationship to risk-taking
behaviors.
AB - PURPOSE: Adults have frequently been concerned about the adverse influence that
music may have on teenagers. This study was designed to examine the relationship
between the intensity of emotional response to music and health risk-taking
behavior in adolescents. METHODS: Consecutive participants from the University of
California, San Diego, Adolescent Medicine Clinics completed a written survey
about music preference, emotional response to music using the Positive Affect
Negative Affect Schedule (PANAS), and a variety of health-risk behaviors. For
each participant, the PANAS scores were summed to give a positive, negative, and
total affect score, and health-risk behaviors were assigned a point value based
on the level of risk and then summed to give a risk score. RESULTS: Health-risk
behavior was found to be correlated with increasing emotional response to music
(r = 0.23), whether those emotions were positive (r = 0.19) or negative (r =
0.24). Strong negative emotional response to music in particular was correlated
with a history of greater risk behavior, particularly among whites (risk score =
14.0). CONCLUSIONS: Our study indicates that subjects who experience strong
negative emotions to music are at an increased risk of participating in a variety
of risk-taking behaviors. Further evaluation of the link between emotional
response to music and health-risk behaviors will be useful in clarifying the
nature of this relationship.
PMID- 9648023
TI - Nipple and areola diameter in Turkish pubertal girls.
AB - The nipple and areola diameter of 498 girls aged 8-17 years were studied with the
aim of finding measurable criteria for sexual maturation, including breast and
pubic hair development during female puberty. All measurements were made holding
a transparent ruler on both sides by the same observer. The smaller of the two
measurements was used in the analysis. Significantly nipple and areola
development occurred between breast stages B1 (2.56 and 14.35 mm), B2 (3.32 and
20.26 mm), B3 (5.21 and 28.84 mm), and B4 (6.28 and 32.03 mm). The nipple and
areola diameter were also significantly greater in pubic hair stage (PH)3 (5.05
and 25.24 mm) with respect to PH2 and PH1 (3.46, 2.62 mm and 19.32, 15.37 mm,
respectively), in PH5 (6.79 and 35.62 mm) with respect to PH4 (6.55 and 32.56
mm). A significant increase in nipple and areola diameter occurs between
premenarchal girls and girls older than 0-2 years postmenarche. Sexual maturation
staging by nipple size and by areola size appears to be feasible for female
adolescent. However, staging by nipple size does not appear to be feasible for B4
and B5 stage, because the incremental gradations are small.
PMID- 9648024
TI - Chemical modification and photograft polymerization upon expanded
poly(tetrafluoroethylene).
AB - Poly(tetrafluoroethylene) (PTFE) films were surface-modified by employing a
reaction solution of benzophenone and sodium hydride in anhydrous
dimethylformamide at a temperature of 150 degrees C for 12 h. Electron
spectroscopy for chemical analysis (ESCA) showed defluorination, oxygen
incorporation, and extensive unsaturation within the treated PTFE surfaces. The
suitably of these reduced PTFE films as substrates for graft polymerization was
initially assessed via photograft polymerization of the sodium salt of
styrenesulfonic acid (SS-Na), which permitted unequivocal surface analysis by the
introduction of a new atom, as well as poly(ethylene glycol) monoacrylate (PEG
Ac). All photograpt polymerization was performed employing ultraviolet
irradiation with 2,2-dimethoxy-2-phenylacetophenone as an initiator. Photograft
polymerization of SS-Na was verified by further reduction of fluorine atomic
content and the appearance of new sulfur and sodium atomic peaks on ESCA survey
spectra, and that of PEG-Ac was verified by further reduction of fluorine atomic
content and increase of atomic percent ratio of O/C from ESCA survey spectra as
well as appearance of a new ester peak on high resolution ESCA C 1s spectra.
Dynamic water contact angles on reduced and PEG-Ac photograft polymerized films
were measured and showed that the PTFE film surface became more hydrophilic after
reduction (from 120 to 89 deg) and the reduced film became more hydrophilic after
photograft polymerization with PEG-Ac (from 89 to 36 deg). Modification of the
complete surface of expanded PTFE (ePTFE), i.e. of the lumenal, outside and pore
surfaces, was performed by employing the reaction described above, except at 105
degrees C for 1 day, followed by photograft polymerization of PEG-Ac. ESCA was
performed on the superficial surfaces (i.e. the lumen and exterior) as well as on
cross-sections of the ePTFE to permit analysis of the pore surfaces. This
analysis showed that both the initial surface reduction and subsequent photograft
polymerization were successful as indicated from F/C and O/C atomic percent
ratios from ESCA survey spectra, from overall peaks shapes of high resolution
ESCA C 1s spectra and from generation of new ester peaks on high resolution ESCA
C 1s spectra of ePTFE graft polymerized with PEG-Ac, which demonstrated an O/C
atomic percent ratio close to that of PEG-Ac homopolymer. Low voltage scanning
electron microscopy confirmed minimal morphological damage to the ePTFE
microstructure after reduction and graft polymerization. The approach explored
thus provides a means for modulation of biological interactions at ePTFE surfaces
with only minimal modification of material morphology, with some surface texture
appearing on a length scale of 50-100 nm.
PMID- 9648025
TI - Surface grafting of poly(ethylene glycol) onto poly(acrylamide-co-vinyl amine)
cross-linked films under mild conditions.
AB - Poly(ethylene glycol) (PEG) was grafted onto poly(acrylamide-co-vinyl amine)
(poly(AM-co-VA)) film using tresylated PEG (TPEG) at 37 degrees C in aqueous
buffers (pH 7.4) with a view to surface-modifying microencapsulated mammalian
cells. Poly(AM-co-VA) film was synthesized by Hofmann degradation of a cross
linked poly(acrylamide) film. Conversion to vinyl amine on the surface of the
film was approximately 50%, but bulk conversion was not observed; surface
specificity was thought to be the result of cleavage of aminated polymer chains
at the surface due to chain scission. Reaction between primary amine and TPEG
gave a graft yield of 2 mol% (based on XPS) with respect to available surface
amine groups, equivalent to 54 mol% ethylene oxide based on monomer units.
Physical adsorption of non-activated polymer was done under identical conditions
as a control and the difference in oxygen content was significant compared to
TPEG. The type of buffer agent and buffer concentration did not influence graft
yields. This graft reaction, which was completed in as little as 2 h was
considered to be mild enough to be used for a surface modification of
microcapsules containing cells without affecting their viability. Such a surface
modification technique may prove to be a useful means of enhancing the
biocompatibility of microcapsules (or any tissue engineering construct) even
after cell encapsulation or seeding.
PMID- 9648026
TI - Ectopic bone formation induced by biodegradable hydrogels incorporating bone
morphogenetic protein.
AB - Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross
linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP
2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2
incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP
2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial
burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous
implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back
of mice, the radioactivity remaining in the hydrogels was measured to estimate
the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the
hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution
form was cleared from the injected site within one day, completely disappearing
within 3 days. Ectopic bone formation studies demonstrated that BMP-2
incorporating gelatin hydrogels exhibited a more potent ability for bone
induction than solution injection of BMP-2. This finding indicates that enhanced
retention of BMP-2 is promotes its ability to induce ectopic bone formation.
PMID- 9648027
TI - Complexation of basic fibroblast growth factor with gelatin.
AB - Polyion complexation between basic fibroblast growth factor (bFGF) and gelatin
was studied by the turbidity change of mixed solution, heparin high performance
liquid affinity chromatography (HPLAC), and isoelectric electrophoresis. When an
aqueous solution of acidic gelatin with an isoelectric point (IEP) of 5.0 was
mixed with that of bFGF, the turbidity of the mixed solution increased with time,
whereas basic gelatin with and IEP of 9.0 did not cause any solution turbidity. A
maximum turbidity of the mixed bFGF and acidic gelatin solution was observed
around a bFGF/gelatin molar ratio of 1.0, irrespective of the gelatin
concentration and solution temperature. The solution turbidity decreased with an
increase in the ionic strength of the mixed solution. Complexation of bFGF with
acidic gelatin was slower than that with poly(acrylic acid) probably because of
the lower density of gelatin negative charge than that of poly(acrylic acid).
HPLAC study revealed that complexation of bFGF with the acidic gelatin reduced
the affinity of bFGF for heparin, in contrast to the basic gelatin, although the
extent became smaller with the increasing ionic strength of the solution. An
electrophoretic experiment showed that the IEP of bFGF shifted to a lower value
after its gelatin complexation. These findings indicate that an electrostatic
interaction is the main driving force for the complexation between acidic gelatin
and basic bFGF.
PMID- 9648028
TI - Comparative study of the use of poly(glycolic acid), calcium alginate and
pluronics in the engineering of autologous porcine cartilage.
AB - New cartilage formation has been successfully achieved by technology referred to
as tissue engineering. Polymers and hydrogels such as poly(glycolic acid),
calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used
as cell carriers to regenerate cartilage in the nude mouse model. The next step
toward human applications of engineered cartilage is to demonstrate their
potential in immunocompetent animal models. This study compared the suitability
of three polymers for generating tissue engineered elastic cartilage using
autologous cells in an immuno-competent porcine animal model. Auricular cartilage
was obtained from pigs. Chondrocytes were isolated onto fiber based poly(glycolic
acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at
constant concentrations. Chondrocyte-polymer constructs were either implanted
(PGA) or injected (calcium alginate and pluronic) as autologous implants
subcutaneously into the pigs from which the cells had been isolated. Specimens
were harvested and analyzed grossly and historically after 6 weeks in vivo. All
explants demonstrated cartilage formation to a variable degree. When using PGA or
calcium alginate, the overall histological appearance of the tissue formed is
that of fibrocartilage with thick bundles of collagen dispersed in the tissue.
When using pluronics as scaffold, histologic features resemble those of native
elastic cartilage, showing a more organized arrangement of the cells, which seems
to correlate to functional properties as elastin presence in the tissue
engineered cartilage. Elastic cartilage engineered in an immunocompetent animal
model varies with the type of polymer used. The behavior of the cell-polymer
constructs is not fully understood and outcome seems to be related to several
factors, including inflammatory reaction. Further studies with similar models are
needed to determine the feasibility of engineering tissue generated from
different cell-polymer constructs prior to human application.
PMID- 9648029
TI - Periodontal ligament cell culture on the hydrophobic substrate coated with
proteins of periodontal ligament fibroblast-conditioned medium.
AB - In regenerating periodontal ligament (PDL) around the root of an artificial
tooth, an important role is played by some physiologically active substance that
promotes adhesion of the cells to the surface of the tooth root and induces cell
proliferation and differentiation. In this study, the supernatant of the
conditioned medium (CM) of dog periodontal ligament fibroblast (DPLF) was
fractionated using an ion exchange chromatography-diethylaminoethyl (IEC-DEAE)
column. DPLFs were cultured on hydrophobic dishes coated with each fraction. Cell
proliferative activity and alkaline phosphatase (ALPase) activity, including
electron microscopic features of the contact surface between the cells and the
dish, were investigated. The DPLF-CM was separated by IEC-DEAE column into six
fractions. Each fraction promoted an increase in DNA content and ALPase activity
of the cultured DPLF, and especially remarkable were fractions 2 and 3. Fraction
2 at a molecular weight (Mw) of 210, 160, 85, 50 and 22 kD, and fraction 3 at Mw
= 21 and 23 kD contained the type of proteins not found in other fractions.
Electron microscopic analysis revealed that the cells in the coating group were
in close contact with the surface of the dishes and that fine fibers protruding
from the cell membrane clinged to the dishes. In the control group, a wide gap
between the cells and the dishes was observed. These findings suggest that the
DPLF-CM fractions contain specific physiological activating factors that induce
proliferation and differentiation as well as cell adhesion of the DPLF cells.
PMID- 9648030
TI - Creating biomimetic micro-environments with synthetic polymer-peptide hybrid
molecules.
AB - In designing polymers that can act as tissue engineering templates it is
beneficial to consider methods of mimicking the natural support structures used
by the human body to guide the behavior and development of cells within tissues.
The well-known RGD cell adhesion ligand provides a simple mechanism of creating
polymer surfaces that mimic the extracellular matrix. This paper considers the
methods that have been used to attach such motifs to synthetic polymers. In
general there are two strategies: the formation of polymer-peptide hybrid
molecules, or the immobilization of the ligand on the fabricated surface of the
polymer. The three major synthetic strategies of creating polymer-peptide hybrids
are reviewed.
PMID- 9648031
TI - Empirically supported psychosocial interventions for children: an overview.
AB - Discusses issues related to the identification of psychosocial interventions for
children that have demonstrated efficacy. Recent debate concerning differences
between clinical trials research and clinical practice is summarized, including
the tradeoff between interpretability (internal validity) and generalizability
(external validity) of outcome studies. This article serves as an introduction to
the special issue containing articles that have as their focus the identification
of empirically supported psychosocial interventions for children as part of a
task force. The article provides an overview of the history, agenda, and
methodology used by the task force to define and identify specific empirically
supported interventions for children with specific disorders. Whereas a number of
well-established or probably efficacious interventions are identified within the
series, more work directed at closing the gap between research and practice is
needed.
PMID- 9648032
TI - Applying the criteria for empirically supported treatments to studies of
psychosocial interventions for child and adolescent depression.
AB - Reviews the psychosocial treatment outcome studies for depressed children and
adolescents and concludes that psychosocial interventions are effective at
posttreatment and follow-up in reducing depressive symptoms/disorders in clinical
and nonclinical samples of youth, regardless of treatment modality or extent of
parental involvement. The article then examines the extent to which each study
conforms to the guidelines set forth by the Task Force on Promotion and
Dissemination of Psychological Procedures (1996) for well-established and
probably efficacious interventions. Results of this analysis indicate only 2
series of studies that meet criteria for probably efficacious interventions and
no studies that meet criteria for well-established treatments. Finally, the
advantages and disadvantages of applying criteria for empirically supported
treatments to identify good treatments for depressed youth are discussed, the
importance of devising developmentally and culturally sensitive interventions
targeted to the unique needs of each child is highlighted, and recommendations
for future research that is informed by clinical practice and empirical findings
are offered.
PMID- 9648033
TI - Empirically supported treatments for children with phobic and anxiety disorders:
current status.
AB - Reviews the empirically supported status of behavioral and cognitive-behavioral
interventions in the treatment of childhood phobias and anxiety disorders. For
childhood phobias, it is concluded that imaginal desensitization, in vivo
desensitization, filmed modeling, live modeling, and cognitive-behavioral
interventions that use self-instruction training are probably efficacious and
that participant modeling and reinforced practice are well established. For
anxiety disorders, only cognitive-behavioral procedures with and without family
anxiety management (FAM) were found to be probably efficacious. However, much of
the support for these procedures comes from analogue studies conducted in
research laboratory or school settings, delivered in small-group format and, not
infrequently, with nonclinically referred children. Additional research that
examines high-strength interventions with clinic-referred children is
recommended. Furthermore, research that examines the pathological processes
involved in the onset and maintenance of phobic and anxiety disorders as well as
the change processes used to treat these disorders is called for.
PMID- 9648034
TI - Empirically supported comprehensive treatments for young children with autism.
AB - Describes treatment of autism, a severe, chronic developmental disorder that
results in significant lifelong disability for most persons, with few persons
ever functioning in an independent and typical lifestyle. Within the past decade,
a number of studies have reported significant changes in the outcomes of very
young children with autism following intensive comprehensive treatment. The
criteria for empirically supported treatments, as described by Lonigan, Elbert,
and Johnson (this issue), were applied to reports of eight treatment efficacy
studies published in peer-reviewed journals. Whereas positive outcomes are
reported in every case, the field does not yet have a treatment that meets the
present criteria for well-established or probably efficacious treatment.
Hypothesized variables affecting outcomes that need to be rigorously tested
include age at start of treatment, type of treatment used, intensity of
treatment, and IQ and language levels at the start of treatment.
PMID- 9648035
TI - Effective psychosocial treatments of conduct-disordered children and adolescents:
29 years, 82 studies, and 5,272 kids.
AB - Reviews psychosocial interventions for child and adolescent conduct problems,
including oppositional defiant disorder and conduct disorder, to identify
empirically supported treatments. Eighty-two controlled research studies were
evaluated using the criteria developed by the Division 12 (Clinical Psychology)
Task Force on Promotion and Dissemination of Psychological Procedures. The 82
studies were also examined for specific participant, treatment, and
methodological characteristics to describe the treatment literature for child and
adolescent conduct problems. Two interventions were identified that met the
stringent criteria for well-established treatments: videotape modeling parent
training program (Spaccarelli, Cotler, & Penman, 1992; Webster-Stratton, 1984,
1994) and parent-training programs based on Patterson and Gullion's (1968) manual
Living With Children (Alexander & Parsons, 1973; Bernal, Klinnert, & Schultz,
1980; Wiltz & Patterson, 1974). Twenty of the 82 studies were identified as
supporting the efficacy of probably efficacious treatments.
PMID- 9648036
TI - Empirically supported psychosocial treatments for attention deficit hyperactivity
disorder.
AB - Reviews and evaluates psychosocial treatments for attention deficit hyperactivity
disorder (ADHD) in children and adolescents according to Task Force Criteria
(Lonigan, Elbert, & Johnson, this issue). It is concluded that behavioral parent
training and behavioral interventions in the classroom meet criteria for well
established treatments. Cognitive interventions do not meet criteria for well
established or probably efficacious treatments. Issues regarding the evaluative
process are discussed and future directions for psychosocial treatment for ADHD
are outlined.
PMID- 9648037
TI - Finding, evaluating, refining, and applying empirically supported treatments for
children and adolescents.
AB - Structured child and adolescent treatments, tested through controlled clinical
trials, have produced beneficial effects in hundreds of studies. By contrast, the
limited pool or research on traditional clinical treatments raises doubts about
their effectiveness. Thus, identification of empirically supported treatments may
contribute something of real value to clinical practice and training. The Child
Task Force report represents an important initial step in this direction. Here we
offer both praise and critique, suggesting a number of ways the task force
process and product may be improved. In addition, we suggest several ways to
strengthen and enrich the clinical trials research available to the Task Force,
emphasizing the need to test empirically supported treatments with referred youth
in practice settings.
PMID- 9648038
TI - Current progress and future plans for developing effective treatments: comments
and perspectives.
AB - Examined the conclusions and implications of articles in this special issue.
Treatments can be differentiated on their empirical basis and, for the problems
reviewed, one can identify treatments of choice. To build on the documented
advances, we provide a blueprint for progress in treatment research. The
blueprint focuses on a series of steps that involve conceptualization of clinical
dysfunction and treatment, supportive research on these conceptual views, careful
specification of treatment, evaluation of treatment outcome, and tests of
mediators and moderators of treatment. To improve research, we recommend
expanding assessment, addressing a broad range of questions about treatment,
attending to measures of clinical significance, replicating key findings, and
investigating the transportability of the findings to service-oriented clinical
settings.
PMID- 9648039
TI - Psychosocial determinants of alcohol use among minority youth living in public
housing developments.
AB - Youth residing in low income, inner city, public housing developments might be
extremely vulnerable to psychosocial risk factors associated with alcohol use. In
this study, we developed and tested a model of alcohol etiology with 624 African
American and Hispanic 7th graders residing in public housing developments. The
students completed questionnaires concerning their alcohol use, social influences
on their drinking, their drinking attitudes and knowledge, their psychosocial
skills, and demographic and behavioral control information. Logistic regression
analyses indicated that social influences from adults, friends, and family
members predicted alcohol use. Individual psychosocial characteristics, e.g.,
drinking refusal, lowered the odds of drinking. These findings imply that
effective prevention approaches targeting minority urban youths residing in
public housing developments should provide them with an awareness of social
influences to drink, correct misperceptions concerning the prevalence of
drinking, and train them in relevant psychosocial skills.
PMID- 9648040
TI - Infant screening: the usefulness of the Bayley Infant Neurodevelopmental Screener
and the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale.
AB - We assessed the usefulness of the Bayley Infant Neurodevelopmental Screener
(BINS) and the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone
Scale (CAT/CLAMS) for screening high-risk infant populations in a sample of 78
infants followed after premature birth and/or perinatal insults. Both measures
were highly correlated with the Bayley Scales of Infant Development-II, but
sensitivity and specificity analyses revealed disparities related to the tests
administered and the cutoffs used. The BINS had optimal sensitivity (true
positives) of 90% when referral was made for a BINS score of high or moderate.
The CAT/CLAMS had excellent specificity (true negatives) of 95% to 98% but poor
sensitivity (5%-36%). Until the cutoff issue can be clarified, clinicians should
be cautious in using the CAT/CLAMS as the primary screening instrument in
settings in which early identification of infants with developmental problems is
the main goal.
PMID- 9648041
TI - Examination of DSM-IV criteria for attention deficit/hyperactivity disorder in a
county-wide sample.
AB - This study replicated, in the subsequent academic year, teacher-reported
prevalence rates for attention deficit/hyperactivity disorder (ADHD) based on DSM
IV. Teachers in grades K-5 in a Tennessee county (10 schools, 214 teachers, and
4323 children) completed questionnaires on all their students consisting of the
DSM-IV symptoms for disruptive behavior disorders, except for eight conduct
disorders symptoms, seven symptoms screening for anxiety or depression, ratings
of performance, and questions about the presence of ADHD, stimulant medication
treatment, and behavioral or academic problems. The prevalence rates were 16.1%
for ADHD-all types, 8.8% for ADHD-inattentive type (AD), 2.6% for ADHD
hyperactive/impulsive type (HI), and 4.7% for ADHD-combined type and 6.8, 3.2,
0.6, and 2.9%, respectively, when impairment was taken into consideration. The
rates of problems differed mostly between ADHD-AD AND ADHD-HI (30% vs. 68%) for
behavior and (56% vs. 16%) for academics. Few (11-33%) had an ADHD diagnosis or
were treated with stimulant treatment (8-26%). DSM-IV criteria are likely to
increase the prevalence but may better characterize the heterogeneity of this
disorder.
PMID- 9648042
TI - Infant predictors of cognitive development in an undernourished Kenyan
population.
AB - Assessments of infant sociability, motoric capacities, and nutritional factors
were performed to elucidate early influences on infant development in an
undernourished Kenya population. In this longitudinal study, infant social skills
were assessed using both the Bayley Behavior Record and home observations during
the first 6 months of the infants' lives. Abilities were measured using an
adapted version of the Bayley scales of infant development at 6 and 30 months,
and a short battery of cognitive measures at 5 years. Infant size measurements
were used as indicators of infant nutritional status. Shorter and lighter
infants, and those infants showing growth faltering in weight attainment, were
significantly less sociable at 6 months than infants who were taller and
maintained heavier weights. Infants with smaller arm circumferences displayed
lower motor scores at 6 months and lower Bayley mental scores at 30 months than
infants with greater arm circumference. Furthermore, infants who were more
motorically able and socially adept at 6 months had higher Bayley scores at 30
months and higher verbal comprehension scores at 5 years.
PMID- 9648043
TI - Parental report of sleep problems in children with attentional and learning
disorders.
AB - This study examined whether parents of children diagnosed with neurodevelopmental
disorders (n = 79) report greater sleep-related problems in their offspring than
do parents of normal community-based children (n = 86) on a research
questionnaire developed to assess sleep and breathing problems, sleepiness, and
behavioral problems. Clinical subgroups included: attention deficit/hyperactivity
disorder (ADHD) (n = 43), learning disabilities (LD) (n = 11), and combined
ADHD/LD (n = 25). Analyses revealed that parents of children with
neurodevelopmental disorders report greater problems along all three dimensions
than parents of normal control children. Sleep-related difficulties were reported
at the same frequency across all three clinical subgroups. No significant
difference between clinical and control groups was noted, however, in the
reported length of sleep on weeknights. These preliminary findings suggest that
sleep-related problems need to be routinely reviewed as part of the clinical
evaluation of neurodevelopmental problems, because they may contribute to and/or
exacerbate the behavioral manifestation of these disorders.
PMID- 9648044
TI - Stimulant use and the potential for abuse in Wisconsin as reported by school
administrators and longitudinally followed children.
AB - The purpose of this study was to describe stimulant use and abuse as reported by
school administrators and children diagnosed with attention deficit/hyperactivity
disorder or attention deficit disorder inattentive. Five years after being
identified as Ritalin responders, 161 children were surveyed regarding stimulant
use and abuse. School principals in central Wisconsin were also surveyed
regarding stimulant use and policies. No child believed stimulants as prescribed
could lead to abuse. Sixteen percent of the children had been approached to sell,
give, or trade their medication. During school hours, 44% of children and 37% of
schools reported stimulants were stored unlocked. Not all schools had written
policies regarding prescription drugs, and 10% permitted students to carry their
own medication. Monitoring prescription usage, periodic reassessment of efficacy,
and continuing education of family and teaching staff should be part of the
multimodal treatment for this disorder. School policies should be developmentally
sensitive.
PMID- 9648045
TI - Pediatric pain management: program description and preliminary evaluation results
of a professional course.
PMID- 9648046
TI - Twelve-year-old girl with chronic fatigue, school absence, and fluctuating
somatic symptoms.
PMID- 9648047
TI - Psychological aspects of sexually transmitted infection acquisition in adolescent
girls: a developmental perspective.
PMID- 9648048
TI - Apoptosis and PCNA expression induced by prolactin in structural involution of
the rat corpus luteum.
AB - There are two stages of luteal regression. The first stage is functional
regression that is characterized by a decreased production of progesterone
secretion; the second stage of structural involution is referred to as a
structural luteolysis. In rodents, prolactin has a biphasic action on the corpus
luteum. It is luteotrophic, but when exposed to functionally regressed corpora
lutea it causes luteolysis. The objective of the present studies was to examine
mechanisms of prolactin action in structural luteolysis, whether apoptosis is
involved in this process, and to examine the possible association of cell
proliferation signals as mediators of structural luteolysis. Prolactin-induced
structural luteolysis was associated with apoptosis verified by terminal
deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling
(TUNEL). Apoptotic cells made up about 3% of the cells 24 hours after the first
injection of prolactin, a level that remained constant at all stages of
structural luteolysis. Total ovarian weight and DNA content were decreased about
50% in 72 hours after induction of structural luteolysis by prolactin, The
finding of about 3% of cells in apoptosis indicates apoptosis is a rapid process.
Proliferating cell nuclear antigens (PCNA) of luteal cells were significantly
decreased during functional luteal regression, but were conversely increased in
structural luteolysis as shown by western blotting and immunohistochemistry. In
general PCNA expression is reported to be decreased during structural involution,
and there are no reports that have linked excess expression of PCNA with
apoptosis and structural luteolysis. We speculate that an excessive increase in
expression of PCNA which signals activation of cell proliferation creates a
disorder in the signals involved with DNA synthesis. This disorder results in
mitotic catastrophe and in the induction of apoptosis. Therefore the disorder of
cell cycle signals in luteal cells are associated with prolactin induced
apoptosis in structural luteolysis.
PMID- 9648049
TI - Effect of surgery and radiotherapy on visual and endocrine function in
nonfunctioning pituitary adenomas.
AB - The effect of surgery alone or followed by radiotherapy in recovering visual
abnormalities, debulking tumor mass and restoring hormone impairments was
evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA)
subjected to 1-10 yr follow-up. All patients underwent surgery via
transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy
was performed after surgery in 59 of 72 patients with incomplete tumor removal.
The assessment of pituitary function was performed in all patients before and
every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic
assessment was performed before and 3, 6 and 12 months after surgery, then
yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58
patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was
documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal
function recovered in 12 women, visual disturbances improved in 43 patients (15
regained normal vision), pituitary function improved in 8 of 62 patients,
worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of
84 patients. After surgery alone, tumor regrowth was observed in 7 patients
between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in
49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was
documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism
raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is
effective only in a minority of patients (14.3%) and radiotherapy causes
hypopituitarism in rather the totality of patients after 10 yr. The prevalence of
tumor regrowth was similar in irradiated ones (15%) and non irradiated patients
(28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested
after surgery so that radiotherapy can be performed promptly on the basis of
clinical data, tumor regrowth and/or invasiveness documented at histology.
PMID- 9648050
TI - Lack of effect of the dopamine D1 antagonist, NNC 01-0687, on unstimulated and
stimulated release of anterior pituitary hormones in males.
AB - Dopamine in humans inhibits the secretion of luteinizing hormone (LH), follicular
stimulating hormone (FSH), thyroid stimulating hormone (TSH) and prolactin (PRL),
and is a stimulator of growth hormone (GH) secretion. Dopamine-D1 receptor
stimulation with fenoldopam increases basal PRL levels, suppresses TSH, and
increases gonadotropin releasing hormone (LHRH) induced LH release. We have
investigated the effect of a dopamine D1-receptor antagonist, NNC 01-0687, on the
secretion of anterior pituitary hormones. In 8 healthy males NNC 01-0687 and
placebo were administered orally in a double-blind placebo controlled cross-over
study for three days with a wash-out period of 14 days. Hormonal responses (PRL,
LH, FSH, GH, TSH, thyroid hormones and testosterone), unstimulated and LHRH/TRH
stimulated, were studied on days 1 and 3. No significant difference (p > 0.05)
between placebo and active periods was found neither in unstimulated nor in
stimulated hormone concentrations expressed in absolute values, percent change of
before, incremental values and area under the curve. These results suggest that
the neuronal DA-D1 activity is not activated during basal conditions in healthy
male subjects.
PMID- 9648051
TI - Pituitary apoplexy in acromegaly, a long-term follow-up study in two patients.
AB - Pituitary apoplexy is a serious complication in about 3% of patients with a
pituitary adenoma. Very often, the diagnosis of a functioning or non-functioning
adenoma is made in retrospect. In this report, we describe two patients in whom
the diagnosis of acromegaly was made before the apoplexy. In one patient,
surgical intervention was necessary because of remaining clinical and biochemical
activity; in the other patient conservative follow-up was pursued. Seven and nine
years after apoplexy, respectively, the patients were clinically and
biochemically in remission. During the follow-up, three and five years after
apoplexy, respectively, the patients underwent a 10-min venous sampling procedure
for 24 hours, and the GH secretory profile was investigated with multiparameter
deconvolution analysis and by approximate entropy (ApEn), a scale- and model
independent regularity measure. The deconvolution analysis revealed an increased
basal (nonpulsatile) GH secretion rate, while the total 24 h secretion rate was
normal compared with 13 healthy male control subjects. ApEn was much larger for
each patient than for any control subject value, indicating markedly more
irregular GH secretion. We hypothesize that these subtle abnormalities are caused
by non-specific damage as a result of vascular insult, leading to abnormal
vascular supply, or abnormal autocrine and paracrine GH regulation within the
remaining gland.
PMID- 9648052
TI - Typical hormonal profiles are accompanied by increased immunoreactivity of theca
folliculi steroid 17 alpha-hydroxylase P450 in polycystic ovary syndrome.
AB - The localisation and expression of steroid 17 alpha-hydroxylase had been studied
in ovaries obtained from 40 patients in whom polycystic ovary syndrome (PCO) was
diagnosed, and in 15 normal ovaries. In patients, elevated serum LH and
testosterone and normal FSH, prolactin and dehydroepiandrosterone levels were
recorded. Serum oestradiol concentration was slightly decreased.
Immunohistochemical staining with the use of antibody directed against human
cytochrome P450c17 (CYP17) revealed that in polycystic as well as in normal
ovaries, steroid 17 alpha-hydroxylase is localised mainly in the thecal cells of
atretic follicles and in the interstitial cells of the stroma. Greater intensity
of the immunohistochemical reaction in the polycystic ovaries than in normal
controls, indicates a higher concentration of CYP17 and suggests increased
expression of steroid 17 alpha-hydroxylase. It is postulated that the increased
expression of ovarian steroid 17 alpha-hydroxylase is an important contributory
factor in the pathogenesis of PCO.
PMID- 9648053
TI - Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and
testicular steroidogenesis in male hypercholesterolemic patients.
AB - To evaluate the influence of an hydrophilic statin, pravastatin, on adrenal and
testicular steroidogenesis and spermatogenesis, eight male hypercholesterolemic
patients were studied. All patients observed a hypocholesterolemic diet and
received placebo for 4 weeks followed by pravastatin (20 mg/die) for 6 months.
Before, during (4th-5th week) and at the end (23th-24th week) of active
treatment, CRH (1 microgram i.v.), ACTH (Synacthen 250 micrograms i.v.) and human
CG (HCG 3000 IU i.m.) tests were performed in addition to semen analysis.
Pravastatin significantly reduced total cholesterol (20.3%), calculated LDL
cholesterol (24.6%) and apolipoprotein B (10.5%, increased apolipoprotein A1
(16.1%) and did not influence plasma HDL-cholesterol and triglycerides. Basal
plasma cortisol, aldosterone, androstenedione, testosterone and oestradiol did
not change under active treatment. Pravastatin administration affected neither
adrenal hormone responses to CRH and ACTH or testicular response to HCG nor
spermatogenesis in respect of motility, morphology and sperm count. In
conclusion, long-term pravastatin treatment, at doses effective in improving
lipid profile, did not influence testicular reproductive and endocrine function
and did not interfere with basal and stimulated adrenal activity of male
hypercholesterolemic patients.
PMID- 9648054
TI - Urinary free deoxypyridinoline levels during childhood.
AB - Free urinary deoxypyridinoline (DPD) levels, corrected for the urinary
concentration of creatinine (nmol/mmol), were determined in 144 healthy children
(76 males and 68 females, mean age +/- SE: 9.1 +/- 0.2 yr, age range: 5.1-14.0
yr) in order to detect the possible age-related changes of this reliable index of
bone resorption activity and the relationship between free DPD, gender and
pubertal development. Multiple regression analysis revealed that most of the
variation in DPD levels was explained by chronological age (coefficient: 2.89, p
< 0.02), whereas sex and pubertal stage did not add significance to the variance.
Urinary DPD levels were similar in males (24.7 +/- 1.8 nmol/mmol urinary
creatinine) and females (24.2 +/- 2.0 nmol/mmol urinary creatinine) and
significantly higher (p < 0.02) in pubertal (Tanner stage II-V: 28.6 +/- 2.8
nmol/mmol urinary creatinine) than in prepubertal children (22.4 +/- 1.4
nmol/mmol urinary creatinine), both in males and in females. The pattern of DPD
levels was clearly different between females and males, the maximum increase
being evident at Tanner stage II-III (mid-puberty) in females and at Tanner stage
IV-V (mid-late puberty in males. The increase of DPD paralleled the elevation of
urinary GH (pmol/mmol urinary creatinine), a non-invasive and acceptable index of
physiological GH secretion, observed during the pubertal growth spurt. The
progressive increase of urinary GH in older children was not followed by a
further stimulation of bone resorption. Although the relationships between
urinary, GH and DPD need to be better investigated, it seems plausible to
hypothesize that the determination of urinary free DPD, as a marker of GH action
on bone, might have some potential in the follow-up of growth promoting
treatments, such as GH.
PMID- 9648055
TI - Extreme but asymptomatic hypergastrinemia with gastroparesis in a young woman
with insulin dependent diabetes mellitus.
AB - Overt diabetic gastroparesis is a rare long-term complication of diabetes,
probably resulting from autonomic neuropathy of vagus nerve. It is now clear that
neural damage plays a pivotal role in the pathogenesis of the disease. Some
studies showed high basal gastrin levels in patients with diabetic gastroparesis,
but the clinical meaning of this observation is still unclear. We report the case
of a young woman with Insulin Dependent Diabetes Mellitus (IDDM) who was referred
to evaluate nausea and vomiting associated to ketoacidosis. Our hypothesis of
autonomic neuropathy with gastroparesis was confirmed. We observed a progressive
increase in fasting gastrin concentration (20-fold normal values) in the absence
of any clinical and laboratory signs of Zollinger-Ellison (ZE) syndrome. The
increasing vomiting induced a severe state of cachexia, which required total
parenteral nutrition for a long period. All therapeutic approaches were
unsuccessful, and the patient rapidly died, suggesting a possible link between
the severity of the clinical picture and the gastrin plasma levels.
PMID- 9648056
TI - Cushing's syndrome complicated by multiple opportunistic infections.
AB - The case history of a 56-year-old man is described who suffered from severe
adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome. The clinical
course was complicated by simultaneous infections with Pneumocystis carinii,
Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes
simplex, which proved to be fatal. A study of the literature shows that
opportunistic infections in endogenous Cushing's syndrome are associated with
severe cortisol excess and carry a high mortality. Opportunistic infections are
most prevalent in the ectopic ACTH syndrome explained by the very high plasma
cortisol concentrations in this condition. Infections with Aspergillus species,
Cryptoccus neoformans, Pneumocystis carinii and Nocardia asteroides predominated.
Cushing's syndrome with a very high plasma cortisol concentration causes a severe
immunocompromized state. Prompt evaluation of the cause of the hypercortisolism,
initiation of cortisol lowering therapy, primary prophylaxis for Pneumocystis
carinii infection when plasma cortisol exceeds 2500 nmol L-1 and a search for
concomitant infectious disease is recommended.
PMID- 9648057
TI - Graves' disease after percutaneous ethanol injection for the treatment of
autonomous thyroid adenoma.
PMID- 9648058
TI - Ischemic renal diseases: new insights into old entities.
AB - Vascular nephropathies are a steadily increasing cause of end-stage renal
failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features
in the hypertensive patient. This is especially true for blacks of African
descent, in whom hypertension and nephrovasculopathies are a major cause of renal
insufficiency. That primary hypertension leads to renal vascular lesions,
glomerular obsolescence and interstitial fibrosis has long been established. It
should not, however, obscure the fact that renal vascular lesions can be observed
in animal models as well as in some humans, especially young blacks, in the
absence of, or anticipating the onset of hypertension. This leads to considering
the hypothesis that nephroangiosclerosis might stem from a genetic defect in the
renal vascular bed and that this defect is strongly associated with the
hypertensive trait. Atherosclerotic renal disease is a major, potentially
treatable cause of chronic renal disease is a major, potentially treatable cause
of chronic renal failure, especially in whites. It leads to renal atrophy, but
the ischemic kidney retains a vigorous potential for tubular cell regeneration,
which pleads for early recognition and treatment. Recent data suggest that renal
ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism,
ranks among the multiple causes of secondary focal segmental glomerulosclerosis.
Irrespective of its initial mechanism, ischemia induces renal fibrosis, the
pathophysiology of which is centered on increased generation of angiotensin II.
Finally, renal vascular lesions are commonly observed in the course of various
nephropathies, even in the absence of hypertension, and the relationship between
these lesions and the unfavorable prognosis of glomerulopathies, especially
primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA
glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum
of nephrovasculopathies opens perspectives for investigating, understanding and
treating a major mechanism of progressive renal insufficiency.
PMID- 9648059
TI - In vitro branching tubulogenesis: implications for developmental and cystic
disorders, nephron number, renal repair, and nephron engineering.
AB - Branching tubulogenesis of the ureteric bud is critically important for kidney
development. Recent findings using three-dimensional cell culture systems for in
vitro branching tubulogenesis are likely to shed light on the mechanisms of
ureteric bud morphogenesis. Here, we try to unify these findings with those
obtained using genetic approaches and organ culture of the embryonic kidney into
a working model of ureteric bud branching tubulogenesis. It appears that the
balance between branching tubulogenesis facilitating growth factors such as
epidermal growth factor receptor ligands, hepatocyte growth factor, insulin-like
growth factors, and inhibitory growth factors such as transforming growth factor
beta family members may regulate branching morphogenesis. Growth factors induce
epithelial cell proliferation, migration, and modulate the expression of a
variety of proteins. Downstream in the growth factor-mediated tubulogenesis
pathway, extracellular proteases, protease inhibitors, extracellular matrix
proteins, and integrins are likely to act as effectors and regulators of
branching tubulogenesis. Discussed in some detail are the relevance of insights
gleaned from in vitro models of branching tubulogenesis to congenital urogenital
abnormalities, cystic kidney diseases, oligonephropathies and hypertension,
tubular cell regeneration after injury, and tubular engineering.
PMID- 9648060
TI - Transplantation of developing metanephroi into adult rats.
AB - BACKGROUND: Transplantation of developing metanephroi into adult hosts has been
proposed as a means to augment host renal function. METHODS: We implanted whole
metanephroi from embryonic day 15 (E15) rats subcapsularly in kidneys or into the
omentum of non-immunosupressed adult rat hosts. At the time of implantation, some
host rats underwent unilateral nephrectomy (UNX) or unilateral nephrectomy and
partial contralateral renal infarction (1 1/2 NX). E15 metanephroi contained only
metanephric blastema, segments of ureteric bud, and primitive nephrons with no
glomeruli. RESULTS: Four to six weeks post-implantation, metanephroi from E15
rats had enlarged, become vascularized, and had formed mature tubules and
glomeruli. Ureters of metanephroi transplanted into the omentum were anastomosed
to hosts' ureters that remained after UNX. Four weeks following
ureteroureterostomy, the contralateral kidney was removed. Inulin clearances of
seven metanephroi implanted into UNX hosts averaged 0.11 +/- 0.02
microliters/min/100 g (2.42 +/- 0.70 microliters/min/g kidney wt) and the
creatinine clearances averaged 0.65 +/- 0.18 microliters/min/100 g. Metanephroi
weighed 71 +/- 15 mg (approximately 4% of the contralateral native kidney). The
transplanted metanephroi were vascularized by arteries originating from the
omentum. Both weights of transplanted metanephroi (145 +/- 24 mg) and inulin
clearances of transplanted metanephroi (30.1 +/- 8.7 microliters/min/g kidney
weight) were significantly increased in rats that underwent 1 1/2 NX compared to
UNX. In contrast, transplantation of developed kidneys resulted in rejection.
CONCLUSIONS: Our findings establish that functional chimeric kidneys develop from
metanephroi transplanted in adult hosts.
PMID- 9648061
TI - Obstructive nephropathy in the neonatal rat is attenuated by epidermal growth
factor.
AB - BACKGROUND: Obstructive nephropathy is a primary cause of renal failure in
infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal rat
results in reduced renal expression of epidermal growth factor (EGF), renal
tubular epithelial (RTE) cell apoptosis and interstitial fibrosis. We wished to
determine whether these changes could be prevented by exogenous administration of
EGF. METHODS: Thirty-three Sprague-Dawley rats underwent UUO within the first 48
hours of life, and received daily injections of either EGF (0.1 mg/kg/day) or
saline (control) for the following seven days, after which obstructed and intact
opposite kidneys were removed for study. These were compared to 11 sham-operated
rats that received either no injections, EGF injections, or saline injections.
Renal cell proliferation was determined by proliferating cell nuclear antigen,
apoptosis was measured by the TUNEL technique, and the distribution of vimentin,
clusterin, transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth
muscle actin were determined by immunohistochemistry. Tubular dilation, tubular
atrophy, and interstitial collagen deposition were quantitated by
histomorphometry. RESULTS: Compared to controls, EGF treatment increased RTE cell
proliferation in the obstructed kidney by 76%, decreased apoptosis by 80%, and
reduced vimentin, clusterin and TGF-beta 1 immunostaining (all P < 0.05). EGF
treatment reduced tubular dilation by 50%, atrophic tubules by 30%, and
interstitial fibrosis by 50% (all P < 0.05). There was no significant effect of
EGF on renal alpha smooth muscle actin distribution. There was no effect of
saline or EGF injections on kidneys from sham-operated rats for any of the
parameters studied. CONCLUSIONS: We conclude that EGF stimulates RTE cell
proliferation and maturation and reduces apoptosis in the neonatal rat kidney
subjected to chronic UUO. These effects may contribute to the reduction in
tubular dilation, tubular atrophy, and interstitial fibrosis. By preserving renal
development, administration of EGF attenuates the renal injury resulting from
chronic UUO.
PMID- 9648062
TI - Molecular genetics of cystinuria: mutation analysis of SLC3A1 and evidence for
another gene in type I (silent) phenotype.
AB - BACKGROUND: Cystinuria is a hereditary disorder that affects luminal transport of
cystine and dibasic amino acids in kidney and small intestine. Three subtypes
have been defined on the basis of urinary excretion of cystine in obligate
heterozygotes. Mutations in the SLC3A1 gene have been associated with the Type I
phenotype. METHODS: We investigated 20 cystinuria patients from Quebec (8 Type
I/I, 9 Type I/III and 3 Type II/N) for mutations in SLC3A1. DNA was studied by
Southern blotting and by the single strand conformation polymorphism (SSCP)
protocol to identify mutations. Expression of mutations in Xenopus oocytes was
performed to confirm the effect of missense mutations on cystine uptake. RESULTS:
Six novel mutations (2 large deletions, a 2 bp deletion and 3 single bp
substitutions) were identified on the Type I allele. Four missense mutations
(T216M, S217R, R270L and I618M) were expressed in vitro; the first three changes
significantly decreased uptake. CONCLUSIONS: Combined with our previous work, we
have identified 15/16 mutations in SLC3A1 on Type I alleles in the eight Type I/I
patients, but only one SLC3A1 mutation on the nine Type I alleles of the Type
I/III patients. Therefore, we propose that the Type I phenotype could be caused
by mutations in other, as yet unidentified cystinuria genes.
PMID- 9648063
TI - Cystinuria subtype and the risk of nephrolithiasis.
AB - BACKGROUND: Cystinuria patients may be classified into several subgroups based on
the urinary phenotype of heterozygotes. However, the relative risk for
nephrolithiasis and the prevalence of SLC3A1 mutations in these subgroups are
unknown. METHODS: Urinary cystine excretion, age at onset of nephrolithiasis and
nature of SLC3A1 mutations were assessed prospectively in 23 cystinuria patients
identified primarily through the Quebec Newborn Screening Program. Probands were
classified as to cystinuria subtype on the basis of parental urinary cystine
excretion. RESULTS: For classical Type I/I cystinuria, both parents excrete
cystine in the normal range and probands carry two mutations of the SLC3A1 gene
in nearly every case. Between ages 1 to 7 years, mean cystine excretion was high
(4566 +/- 480 microns cystine/g creatinine) and exceeded the theoretic threshold
for solubility on 70% of visits. Four of eight Type I/I patients began forming
stones in the first decade. Type I/III patients (N = 12) excreted less cystine
(1544 +/- 163 mumol cystine/g creatinine), exceeded the threshold of urinary
cystine solubility less frequently (22% of visits) and had no nephrolithiasis in
the first decade; one formed a stone at age 16 years. Only one SLC3A1 mutation
was identified in this group. Two Type II/N cystinuria children were identified.
In these families, the same level of relatively high excretion (> 600 mumol
cystine/g creatinine) was noted in two or three generations, but no SLC3A1
mutations were identified. CONCLUSIONS: Classical recessive Type I/I cystinuria
is genetically and phenotypically distinct from the other subtypes (Type I/III
and Type II/N) identified in our population.
PMID- 9648064
TI - Cytokine interactions promote synergistic fibronectin accumulation by mesangial
cells.
AB - BACKGROUND: The development of glomerulosclerosis has been associated with the
presence of the cytokines transforming growth factor-beta 1 (TGF-beta 1), tumor
necrosis factor-alpha (TNF-alpha) and/or interleukin-1 beta (IL-1 beta), at some
stage in the glomerulus. To better understand the role of these cytokines in the
scarring process their effect on rat mesangial cell fibronectin production was
investigated. METHODS: Mesangial cells were exposed to 10 ng/ml of either TGF
beta 1, TNF-alpha, or IL-1 beta or to TGF-beta 1 in combination with TNF-alpha or
IL-1 beta. Tissue culture supernatants and cell lysates were assayed for
fibronectin. Supernatants were also assayed for TGF-beta 1. Northern blot
analyses probing for fibronectin, transin, TIMP-1 and TGF-beta 1 were carried out
on RNA extracted from mesangial cells exposed to individual and combinations of
cytokines. RESULTS: Individually these cytokines were only able to induce modest
increases in fibronectin protein levels. However, when mesangial cells were
exposed to TGF-beta 1 in combination with either TNF-alpha or IL-1 beta then
fibronectin levels were synergistically up-regulated approximately fivefold over
unstimulated levels. Northern analysis demonstrated that fibronectin mRNA levels
in the combination were also synergistically increased. In contrast, rat transin
gene expression in the combinations was reduced to well below levels induced by
TNF-alpha and IL-1 beta individually. In addition, synergistic up-regulation of
both TGF-beta 1 protein and message by the cytokine combinations was also
observed. TGF-beta 1: TNF-alpha and TGF-beta 1: IL-1 beta induced additive
increases in TIMP-1 (tissue inhibitor of metalloproteinases-1) mRNA levels.
CONCLUSIONS: These data illustrate that complex interactions can occur between
cytokines within the glomerulus modulating both matrix synthetic and degradation
pathways. These could initiate the scarring process and the development of
glomerulosclerosis.
PMID- 9648065
TI - Interleukin (IL)-1 and IL-4 synergistically stimulate NF-IL6 activity and IL-6
production in human mesangial cells.
AB - BACKGROUND: While interleukin (IL)-4 inhibits pro-inflammatory cytokine
expression by human monocytes, we have observed that it potentiates IL-6
production by IL-1-activated human mesangial cells (MC). To study the mechanism
of this cell-type specific interaction between IL-1 and IL-4 in MC, we examined
the effect of both cytokines on the activities of nuclear factor kappa B (NF
kappa B) and nuclear IL-6 NL-IL 6), transcription factors that are essential for
IL-6 gene expression. METHODS: We evaluated IL-6 synthesis, mRNA expression, and
mRNA stability by ELISA, Northern analysis, and the actinomycin D method,
respectively. Activities of NF-kappa B and NF-IL 6 were analyzed by gel shift
assay. RESULTS: IL-4 augmented the IL-1 stimulated IL-6 mRNA levels by about
threefold without altering mRNA stability. IL-1 treatment rapidly induced the
binding activity of NF-kappa B. In contrast, IL-4 did not affect basal and IL-1
induced NF-kappa B activities. Both IL-1 and IL-4 stimulated NF-IL6 activity as
early as 30 minutes after treatment. When MC were treated with both cytokines
together, marked activation of NF-IL6 was observed at five hours. CONCLUSIONS:
These results suggest that simultaneous activation of NF-kappa B and NF-IL6 is
essential for IL-6 gene expression and that IL-1 and IL-4 cooperatively stimulate
MC IL-6 production through their synergistic activation of NF-IL6.
PMID- 9648066
TI - Regulation of cAMP production in initial and terminal inner medullary collecting
ducts.
AB - BACKGROUND: The inner medullary collecting duct (IMCD) is composed of at least
two functionally and morphologically distinct segments, the initial (IMCDi) and
the terminal (IMCDt) portions. However, most studies of receptor signaling have
been performed on cells obtained from the entire inner medulla. The purpose of
this study was to determine whether the patterns of receptor-activated cAMP
accumulation were different between these segments. METHODS: We measured cAMP
accumulation stimulated by vasopressin and isoproterenol, and the effect of
epinephrine in freshly dissected IMCDi and IMCDt segments cultured and IMCDi and
IMCDt cells in primary culture. RESULTS: The maximum response to vasopressin was
twofold higher in fresh IMCDt verus IMCDi (P < 0.05), however, it increased in
cultured IMCDi by 40% verus fresh cells with no change in the response in fresh
verus cultured IMCDt. The maximum response to isoproterenol was small in fresh
cells but increased by five- and sixfold, respectively, in cultured IMCDi and
IMCDt cells. alpha 2-Adrenoceptor stimulation almost completely inhibited both
vasopressin and isoproterenol-stimulated cAMP accumulations in fresh IMCDi and
IMCDt cells, but only partially inhibited either accumulation by 34 to 49% in
cultured cells. CONCLUSIONS: (1) IMCDi and IMCDt cells are both subject to
vasopressin and alpha 2- and beta-adrenergic regulation of adenylyl cyclase
activity; (2) the relative influence of beta-adrenergic, alpha 2-adrenergic and
V2 receptors to affect cAMP accumulation is altered in primary culture versus
freshly dissected IMCD segments, suggesting that caution must be exercised in the
extrapolation of data from cultured IMCD cells to in vivo models.
PMID- 9648067
TI - PAI-1 secretion and matrix deposition in human peritoneal mesothelial cell
cultures: transcriptional regulation by TGF-beta 1.
AB - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of
plasminogen activators in plasma and in peritoneum, impairs plasmin formation
that is essential for the repair processes of the mesothelium damaged by
peritoneal dialysis fluids and peritonitis. The fibrogenetic cytokine
transforming growth factor-beta (TGF-beta) displays variable effects on
extracellular matrix remodeling enzymes and their inhibitors depending on tissues
and cell lines. We previously found an unexpected stimulating effect of TGF-beta
1 on matrix metalloproteinase-9 in peritoneal mesothelial cells. In this study,
we analyzed the effects of TGF-beta 1 on PAI-1 production and deposition in
extracellular matrix. METHODS: We used primary cultured mesothelial cells and a
recently established human peritoneal mesothelial cell line (HMrSV5). Cell
associated and secreted plasminogen activators and their inhibitors were detected
and characterized by substrate gel zymography. PAI-1 was identified by reverse
zymography and by Western blotting, and total PAI-1 was measured by ELISA.
Secreted and cell-associated PA activity was measured by its ability to activate
plasminogen into plasmin, that is, by the release of paranitroaniline from the
plasmin synthetic substrate S-2251. PAI-1 mRNA accumulation was assessed by
Northern blot. In vitro nuclear run-on assays were carried out to determine
whether TGF-beta 1 had transcriptional effects on PAI-1 expression. Finally, the
subcellular distribution of PAI-1 was analyzed by immunofluorescence and by
immunogold silver staining. RESULTS: TGF-beta 1 increased PAI-1 antigen in the
conditioned media of HMrSV5 cells, in a time- and concentration-dependent manner.
This induced a dramatic decrease of free tPA in the cell medium and of membrane
bound uPA, and a parallel increase of high molecular weight PA-PAI complexes.
Consequently, secreted and cell-associated plasminogen activator activities were
considerably reduced. In primary cultured peritoneal mesothelial cells, TGF-beta
1 also induced PAI-1 secretion and the shift of tPA toward high molecular weight
complexes. TGF-beta 1 increased PAI-1 mRNA in a time- and concentration-dependent
manner. This effect was at least in part transcriptional since an approximately
threefold increase in the rate of PAI-1 gene transcription was observed in nuclei
sampled after a four-hour cell exposure to 5 ng/ml TGF-beta 1. Finally, TGF-beta
1 substantially increased the amount of intracellular and matrix-associated PAI
1. CONCLUSIONS: These results suggest that excessive TGF-beta 1 stimulated PAI-1
could prevent appropriate peritoneal healing by impairing the degradation of
fibrin and of unorganized matrix components, and by interfering with cell
migration.
PMID- 9648068
TI - Pirfenidone improves renal function and fibrosis in the post-obstructed kidney.
AB - BACKGROUND: Pirfenidone (PFD) is a novel anti-fibrotic agent that can prevent and
even reverse extracellular matrix accumulation in several organs, as shown by
experimental and clinical studies. Unilateral ureteral obstruction (UUO) is a
well-characterized model of experimental renal disease culminating in
tubulointerstitial fibrosis. METHODS: UUO or sham-operated rats were administered
PFD (500 mg/kg/day) in their food for 21 days to examine the effect on collagen
production. The renal function was measured in the kidney after release of
obstruction which had been maintained for one week to examine the effects of PFD
on restoration after renal dysfunction. RESULTS: The collagen content detected by
hydroxyproline progressively increased in kidney with UUO for 21 days. These
increases were significantly suppressed by administration of PFD. PFD had no
effect on collagen production in sham-operated rats. Expression of mRNA for type
IV and I collagen and matrix metalloproteinase-2 in the cortex increased with
UUO, but was inhibited by PFD treatment. The levels of cortical transforming
growth factor-beta (TGF-beta) mRNA progressively rose with UUO for 21 days, but
this increase also could be suppressed by PFD. Inulin clearance of the obstructed
kidney was markedly depressed and remained low at five weeks after release. A
progressive increase in hydroxyproline content was also observed in the post
obstructed kidney despite the release of obstruction. Administration of PFD
following the release not only attenuated collagen accumulation, but also induced
recovery of the impaired renal function. CONCLUSIONS: These results demonstrate
that PFD can attenuate both renal fibrosis and renal damage in this model, and
suggest that PFD can be clinically useful for preventing progressive,
irreversible renal failure.
PMID- 9648069
TI - Up-regulation of HSP47 in the mouse kidneys with unilateral ureteral obstruction.
AB - BACKGROUND: Unilateral ureteral obstruction (UUO) is a well established
experimental model of renal injury leading to interstitial fibrosis. The
molecular and cellular mechanism(s) of interstitial fibrosis in UUO are beginning
to be elucidated. In the progression of interstitial fibrosis in UUO, up
regulation of collagen synthesis is commonly observed. HSP47 is a collagen
binding stress protein and is thought to be a collagen-specific molecular
chaperone, which plays a pivotal role during the biosynthesis and secretion of
collagen molecules in the endoplasmic reticulum. The synthesis of HSP47 has been
demonstrated to always parallel that of collagen in physiological and
pathophysiological conditions. It is well recognized that renin-angiotensin
system (RAS) is enhanced in the setting of UUO and that enhanced RAS has been
implicated in the pathogenesis of interstitial fibrosis in the obstructed
kidneys. METHODS: To investigate the role of HSP47 in the progression of
interstitial fibrosis in mouse UUO, the expression of HSP47 was examined by
Northern blotting, immunohistochemistry and in situ hybridization in the
obstructed kidneys. To test the possible involvement of enhanced RAS on the HSP47
expression, we examined the effects of lisinopril, an angiotensin converting
enzyme inhibitor, on interstitial fibrosis. HSP47 and type I collagen mRNA
expression. RESULTS: By Northern blot analysis, HSP47 mRNA was significantly up
regulated at 12 hours (about twice that of sham operated kidneys) after the onset
of ureteral obstruction, further increased and stayed at the increased level
until seven days (about 8 times that of sham operated kidneys). HSP47 mRNA and
protein expression were observed in the periglomerular and peritubular
interstitial regions of the obstructed kidneys. Distribution of smooth muscle
alpha actin and type I collagen immunoreactivity were similar to the HSP47
distribution pattern, suggesting that HSP47 was up-regulated in the
myofibroblasts. Lisinopril ameliorated the expansion of cortical interstitium in
the obstructed kidneys at four and seven days after ureteral obstruction. HSP47
mRNA expression was suppressed at four and seven days, whereas type I collagen
mRNA was suppressed only at seven days after the onset of ureteral obstruction.
CONCLUSIONS: These results demonstrate the early and persistent up-regulation of
HSP47 during the progression of interstitial fibrosis in mouse UUO kidneys, and
further suggest the potential role of HSP47 in the pathogenesis of interstitial
fibrosis in the obstructed kidneys. Partial suppression of HSP47 mRNA expression
by lisinopril at day 4 and day 7 after ureteral obstruction suggests that there
are other immediate trigger(s) that induce the HSP47 mRNA expression.
Identification of the molecular mechanism of HSP47 induction during UUO may give
an insight into the novel aspects of the molecular pathophysiology of
interstitial fibrosis in obstructive nephropathy.
PMID- 9648070
TI - Expression of decay accelerating factor mRNA and complement C3 mRNA in human
diseased kidney.
AB - BACKGROUND: Decay accelerating factor (DAF), a product of mesangial cells in
vitro, is expressed on the surface of cells and is a candidate for the focal
suppression of complement activation. It is not clear at present whether the
levels of expression of DAF and intrarenal C3 synthesis correlate with the level
of tissue injury. METHODS: Immunohistochemistry for DAF and C3 and nonradioactive
in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and
C3 mRNA were performed in 22 tissue samples of kidneys from patients with IgA
nephropathy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephritis
(LN), and five normal kidneys. RESULTS: In the normal kidney, DAF was confined to
the juxtaglomerular apparatus and little or no C3 was detected; however, a few
glomerular cells were positive for DAF mRNA but no C3 mRNA positive cells were
detected. In diseased kidneys, DAF and C3 as well as their mRNAs were detected in
mesangial cells, tubular cells and infiltrating cells. Glomerular epithelial
cells and Bowman's capsule cells contained little or no DAF and C3 but were
positive for their mRNAs. The mean percentages of mesangial cells positive for
DAF and C3 mRNAs were 49.3 +/- 11.5% and 50.7 +/- 10.3% in IgAN, and 17.0 +/-
6.3% and 19.4 +/- 9.0% in MN, respectively. The percentage of mesangial cells
positive for DAF and C3 mRNAs among intraglomerular cells correlated positively
with the degree of mesangial proliferation and glomerular sclerosis in IgAN. In
contrast, in LN the percentage of glomerular cells positive for DAF mRNA
correlated negatively with the degree of glomerular injury, while the percentage
of cells positive for C3 mRNA did not change with the progression of the disease.
The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of
glomerular injury in both IgAN and LN. In the tubulointerstitium, the percentage
of cells expressing mRNA, and C3 mRNA/DAF mRNA radio correlated with the degree
of tubular atrophy and interstitial broadening in both IgAN and LN. CONCLUSIONS:
We conclude that DAF and C3 mRNAs are synthesized in human diseased kidneys, and
that a balance between locally synthesized DAF and C3 may be important in the
progression of glomerulonephritis.
PMID- 9648071
TI - Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its
metanephric developmental regulation with respect to MMP-2 and its inhibitor.
AB - BACKGROUND: Extracellular matrix macromolecules regulate morphogenesis of
embryonic organs, and are developmentally regulated. Their expression and
turnover is regulated by matrix metalloproteinases (MMPs). Recently, an
epithelial cell "membrane" associated metalloproteinase (MT-1-MMP) has been
identified that acts as an activator of a "secreted" MMP-2, and is produced by
mesenchymal fibroblasts. The activity of MMP-2 is inhibited by a "soluble" tissue
inhibitor of MMP-2, TIMP-2. The role of MT-1-MMP in renal development is unknown.
METHODS: MT-1-MMP was cloned from embryonic mouse kidney cDNA library, and its
spatio-temporal distribution during development in the context of MMP-2 and
tissue inhibitor of metalloproteinase-2 (TIMP-2) was studied. RESULTS: The cloned
MT-1-MMP exhibited approximately 86% nucleotide sequence homology with human MT-1
MMP, and had a catalytic domain and a zinc binding site preceded by a RRKR furin
recognition motif. A approximately 4.5 Kb MT-1-MMP mRNA transcript was detected,
and its expression was developmentally regulated. A parallel developmental
regulation of MMP-2 mRNA expression was also observed. TIMP-2 expression was also
developmentally regulated, but lagged behind MT-1-MMP and MMP-2. By in situ
hybridization, MT-1-MMP mRNA was seen to be confined to ureteric bud epithelia,
and was absent in the mesenchyme, while MMP-2 was confined to the mesenchyme. MT
1-MMP protein expression was seen on ureteric bud epithelia, induced mesenchyme
and nascent nephrons, and it was highest during mid gestation. Similar spatio
temporal expressions of MMP-2 and TIMP-2 proteins were observed. CONCLUSIONS:
mRNAs of MT-MMP-1 and MMP-2 are expressed in the respective epithelial and
mesenchymal compartments, while their proteins are co-expressed in the epithelia
suggest that MT-1-MMP and MMP-2, in conjunction with TIMP-2, may be involved in
paracrine/juxtacrine epithelial:mesenchymal interactions during
metanephrogenesis.
PMID- 9648072
TI - Local macrophage proliferation in human glomerulonephritis.
AB - BACKGROUND: Local macrophage proliferation has been described in several animal
models of glomerulonephritis (GN), but its significance in human disease is
unknown. METHODS: Double immunostaining for CD68 and the proliferating cell
nuclear antigen (PCNA) was used to identify macrophage proliferation in 84
biopsies from a variety of glomerulonephridities. RESULTS: A small resident
population of glomerular and interstitial CD68+ macrophages was identified in
normal human kidney, of which only 1 to 2% showed evidence of proliferation on
the basis of PCNA expression. A mild macrophage infiltrate, with only occasional
proliferating macrophages, was seen in the less aggressive forms of GN (minimal
change disease, non-IgA mesangioproliferative GN and IgA nephropathy). This was
in sharp contrast to the more aggressive forms of disease (lupus class IV,
vasculitis-associated GN, crescentic GN and mesangiocapillary proliferative GN),
in which the prominent macrophage infiltrates contained many proliferating
macrophages, accounting for 28 to 47% of the total macrophage population.
Macrophage proliferation was largely restricted to areas of severe tissue damage
(glomerular segmental proliferative lesions, crescents and foci of
tubulointerstitial damage), suggesting that local proliferation is a mechanism
for amplifying macrophage-mediated injury. Glomerular and interstitial macrophage
proliferation gave a significant correlation with loss of renal function (P <
0.0001) and histologic lesions (P < 0.0001), but not with proteinuria.
Interstitial T-cell proliferation also gave a significant correlation with loss
of renal function and histologic damage, even though proliferation within the T
cell population was much lower than in the macrophage population. CONCLUSIONS:
This study demonstrates that macrophage proliferation is a feature of the more
aggressive forms of human GN. Local proliferation may be an important mechanism
for amplifying macrophage-mediated renal injury. In addition, the degree of local
macrophage proliferation may be a useful diagnostic and prognostic indicator for
human GN.
PMID- 9648073
TI - Characteristics of urea transport of cells derived from rabbit thick ascending
limb of Henle's loop.
AB - BACKGROUND: The thick ascending limb of Henle's loop (TALH) is thought to be
involved in the regulation of the renal urea gradient. METHODS: We have
characterized the uptake of urea (oil density centrifugation and 2-compartment
culture) and volume regulation (impedance measurement) in highly differentiated
cells derived from rabbit outer medulla. RESULTS: TALH cells exposed to 600
mOsm/liter (300 mM urea) shrunk to 72 +/- 5% of the isoosmotic volume. Due to a
regulatory volume increase (RVI), the cell volume was almost completely regained
at 92 +/- 6% after five minutes. The uptake of 14C-urea in the presence of urea
concentrations up to 600 mM did not show any saturation. In the presence of
phloretin the urea uptake decreased to 69 +/- 14%. The transport was sodium and
chloride independent. Changing the membrane potential caused an increase of
regulatory volume increase and urea uptake. Hyperosmolarity induced by sucrose
(300 mM) and NaCl (150 mM) caused a decrease of urea uptake to 70 +/- 14% and 53
+/- 11%, respectively. The permeability coefficient (P) in a two compartment
culture was P = 1.7 . 10(-6) +/- 0.39.10(-6) cm/second, suggesting a relatively
low permeability. CONCLUSION: Due to the low permeability, it seems impossible to
achieve a physiologically significant participation of the TALH in the urea
circulation within the nephron. However, the results of this study provides
significant hints about the existence of a specific urea transport mechanism that
enables the cell to adapt rapidly to different osmolarities.
PMID- 9648074
TI - Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia.
AB - BACKGROUND: Chronic metabolic acidosis and K+ deficiency increase, while alkali
feeding decreases proximal tubule citrate absorption and metabolism. The present
studies examined the regulation of mitochondrial aconitase (m-aconitase), the
first step in mitochondrial citrate metabolism, in these conditions. METHODS:
Rats were fed appropriate diets, and m-aconitase activity and protein abundance
measured. RESULTS: In chronic metabolic acidosis and chronic K+ deficiency, renal
cortical m-aconitase activity was increased 17% and 43%, respectively. This was
associated with respective 90% and 221% increases in renal cortical m-aconitase
protein abundance. With chronic alkali feeding, there was a 12% decrease in renal
cortical m-aconitase activity, associated with a 35% decrease in m-aconitase
protein abundance. Hepatic m-aconitase activity was not regulated in a similar
manner. There was no regulation of citrate synthase, the enzyme responsible for
mitochondrial citrate synthesis. CONCLUSIONS: These studies demonstrate tissue
specific chronic regulation of renal cortical m-aconitase activity and protein
abundance, which likely contributes to the hypocitraturia and hypercitraturia
seen in these conditions. As m-aconitase is the only step in citrate transport
and metabolism found to be regulated in alkali feeding, its regulation likely
plays a significant role in mediating the hypercitraturia seen in this condition.
PMID- 9648075
TI - No net renal extraction of homocysteine in fasting humans.
AB - BACKGROUND: The pathophysiological mechanism of hyperhomocysteinemia in chronic
renal failure in humans is unknown. The loss of a putative renal homocysteine
extraction in chronic renal failure has been hypothesized as significant
homocysteine uptake has been demonstrated in the normal rat kidney. We studied
homocysteine extraction in the normal human kidney. METHODS: We measured plasma
total (free and protein-bound) and free homocysteine (tHcy and fHcy,
respectively) in arterial and renal venous blood sampled from the aorta and right
side renal vein during cardiac catheterization in 20 fasting patients with normal
renal function. Renal homocysteine extraction was calculated as the arteriovenous
difference divided by the arterial levels times 100%. RESULTS: No significant
renal extraction was demonstrated either for tHcy: 0.9% (SD 5.8; 95% CI -1.8 to
+3.6) or for fHcy: -0.2% (11.0; -5.4 to +4.9). CONCLUSIONS: We conclude that no
significant net renal uptake of homocysteine occurs in fasting humans with normal
renal function. The loss of such uptake, therefore, cannot cause
hyperhomocysteinemia in patients with renal failure.
PMID- 9648076
TI - Concentrating defect in experimental nephrotic syndrone: altered expression of
aquaporins and thick ascending limb Na+ transporters.
AB - BACKGROUND: Several pathophysiological states associated with deranged water
balance are associated with altered expression and/or intracellular distribution
of aquaporin water channels. The possible role of dysregulation of thick
ascending limb NaCl transporters, which are responsible for countercurrent
multiplication in the kidney, has not been evaluated. METHODS: Semiquantitative
immunoblotting and immunocytochemistry were carried out in the kidneys of rat
with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats.
RESULTS: Preliminary studies confirmed the presence of a severe concentrating
defect. Semiquantitative immunoblotting of outer medullary homogenates
demonstrated a marked decrease in the abundance of three thick ascending limb Na+
transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl
cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the alpha 1-subunit
of the Na-K-ATPase. These results are predictive of a decrease in the NaCl
transport capacity of the medullary thick ascending limb and therefore a decrease
in countercurrent multiplication. Immunocytochemistry of outer medullary thin
sections demonstrated broad (but highly variable) suppression of BSC-1 expression
in the outer medullas of adriamycin-nephrotic rats. There was also a large
decrease in outer medullary expression of two collecting duct water channels
(aquaporin-2 and -3) and the major water channel of the thin descending limb of
Henle's loop (aquaporin-1). CONCLUSION: The concentrating defect in adriamycin
induced nephrotic syndrome in rats is a consequence of multiple defects in water
and solute transporter expression, which would alter both the generation of
medullary interstitial hypertonicity and osmotic equilibration in the collecting
duct. Whether a similar widespread defect in transporter expression is present in
idiopathic nephrotic syndrome is, at this point, untested.
PMID- 9648077
TI - Low Na+ diet inhibits Na+ and water transport response to vasopressin in rat
cortical collecting duct.
AB - BACKGROUND: We previously demonstrated that vasopressin (AVP) produces a
sustained increase in Na+ reabsorption by the isolated perfused cortical
collecting duct (CCD) from rats on a normal diet, and that this effect is
synergistic with that of pharmacological doses of deoxycorticosterone (DOC) or
physiological levels of aldosterone. The present experiments examined the effect
of AVP under the more physiological circumstances when plasma aldosterone was
elevated by prior volume depletion. METHODS: Rats were volume depleted by a
single dose of furosemide followed by a low-salt diet (0.3% NaCl) for four to
nine days. Some of these rats were also implanted with a pellet containing 2.5 mg
DOC. Rats in a third group were not injected with furosemide but were implanted
with the DOC pellet and maintained on a standard (approximately 1% NaCl) diet.
CCD were perfused and the lumen-to-bath Na+ flux (JNA), transepithelial voltage
(VT), and osmotic water permeability (Pf) were measured in the presence and
absence of 200 pm AVP. RESULTS: Although Na+ depletion by a single injection of
furosemide and the low salt diet elevated plasma aldosterone and Vt, JNA remained
low and there was a decreased response to AVP in comparison with DOC-treated rats
on a standard diet. In CCD from rats on the low salt-diet with DOC, JNa was less
than observed in CCD from DOC-treated rats on a standard diet. AVP-dependent Pf
in CCD from rats on the low salt-diet, with or without DOC treatment, was also
markedly lower. CONCLUSIONS: We interpret the results to demonstrate that maximal
rates of Na+ reabsorption in the CCD depend not only on the synergistic
stimulatory effects of aldosterone and AVP, but also require normal to high rates
of salt delivery in vivo for the effects of the hormones on Na+ transport to be
maximized in vitro.
PMID- 9648078
TI - Role of endothelin and nitric oxide imbalance in the pathogenesis of hypoxia
induced arterial hypertension.
AB - BACKGROUND: We have recently demonstrated that prolonged hypobaric hypoxia can
lead to a hematocrit-independent sustained arterial hypertension (HTN) in
genetically normotensive Sprague-Dawley rats. The rise in blood pressure in the
hypoxic animals was accompanied by a marked but transient increase in plasma
endothelin level. In addition, hypoxia has been shown to decrease nitric oxide
(NO) production by cultured endothelial cells. This study was designed to test
the hypothesis that hypoxia-induced HTN may be mediated by increased endothelin
and/or decreased NO production. METHODS: Blood pressure, plasma endothelin and
urinary NO metabolites (NOx)were monitored in rats during a 24-hour exposure to
hypobaric hypoxia (air pressure = 390 mm Hg). The results were compared with
hypoxia (air pressure = 390 mm Hg). The results were compared with those obtained
in animals maintained under normoxic condition (control group). To test the
possible role of excess endothelin and depressed NO production, the studies were
repeated using subgroups of animals treated with either an endothelin receptor ET
A/B blocker (L-754,142) or L-arginine. RESULTS: The untreated hypoxic group
exhibited a threefold rise in plasma endothelin and a threefold fall in urinary
NOx, prior to the onset of HTN. Endothelin receptor blockade led to a further
fall in urinary NOx excretion and failed to mitigate HTN. In contrast, L-arginine
supplementation improved the urinary NOx excretion and prevented HTN. Neither
therapy affected the hypoxia-induced erythrocytosis. CONCLUSIONS: We conclude
that hypoxia-induced HTN is associated with depressed NO production and can be
mitigated by L-arginine supplementation.
PMID- 9648079
TI - Free pentosidine and neopterin as markers of progression rate in diabetic
nephropathy. Collaborative Study Group.
AB - BACKGROUND: Patients with diabetic nephropathy experience a progressive and
usually inexorable decline in renal function. The presence of the structurally
defined advanced glycation end product (AGE) pentosidine on tissue and
circulating proteins has been correlated with the severity of diabetic
complications. METHODS: To delineate a role for this AGE in the progression of
diabetic nephropathy, glycohemoglobin and free and protein-bound pentosidine were
measured in baseline stored serum and urine from a subgroup of patients with
diabetes mellitus and proteinuria originally followed by the Collaborative Study
Group Trial. To delineate a potential role for an immune-activation response to
AGEs, the inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP),
and the monocyte activation marker marker neopterin were also measured at
baseline. The patients chosen represented 67 subjects whose creatinine levels had
"doubled" over the course of the study whether or not they later were treated
with captopril, and 67 paired "non-doublers." RESULTS: Baseline disease activity,
as manifested by glycohemoglobin, serum creatinine and degree of proteinuria was
equal in the two groups, as was protein-bound pentosidine and the immune-markers
IL-6 and CRP. At baseline the "doublers" as compared to the "non-doublers" had
elevated serum levels of free pentosidine and neopterin. Baseline increases in
these two parameters were also associated with an increased rate of "doubling" of
serum creatinine by the proportional hazards method. CONCLUSION: Differences in
individual responsiveness to AGEs, as manifested by either the production of free
pentosidine or its release from a protein-bound form, and by evidence of
monocyte/macrophage activation, are associated with progression of diabetic
nephropathy.
PMID- 9648080
TI - Serum homocysteine level and protein intake are related to risk of
microalbuminuria: the Hoorn Study.
AB - BACKGROUND: Microalbuminuria (MA) is a strong predictor of cardiovascular
disease, but its causes are incompletely understood. Hyperhomocysteinemia is a
recently recognized risk factor for cardiovascular disease independent of
established risk factors. It is not known whether hyperhomocysteinemia is
associated with MA, and thus could be a possible cause of microalbuminuria.
METHODS: We studied an age-, sex- and glucose-tolerance-stratified random sample
of a 50- to 75-year old general Caucasian population (N = 680). The urinary
albumin-to-creatinine ratio (ACR) was measured in an early morning spot urine
sample. MA was defined as an ACR > 3.0 mg/mmol. RESULTS: The prevalence of MA was
4.3% (13 of 304) in subjects with normal glucose tolerance, 9.2% (17 of 185) in
impaired glucose tolerance and 18.3% (30 of 164) in non-insulin-dependent
diabetes mellitus (NIDDM); it was 3.7% (15 of 402) in subjects without
hypertension and 17.9% (45 of 251) in those with hypertension. After adjusting
for age, sex, glucose tolerance category, hypertension, dyslipidemia and smoking,
the odds ratio [OR; 95% confidence interval (95%CI)] for MA per 5 mumol/liter
total homocysteine increment was 1.33 (1.08 to 1.63). Additional adjustment for
HbA1c, waist-hip ratio, protein intake and serum creatinine did not attenuate the
association between MA and total homocysteine. A 0.1 g/kg.day increment of
protein intake was also associated with an increased risk for MA after adjustment
for age, sex, classical risk factors and serum total homocysteine [OR (95% CI);
1.20 (1.08 to 1.32)]. CONCLUSION: Both hyperhomocysteinemia and protein intake
are related to microalbuminuria independent of NIDDM and hypertension.
Hyperhomocysteinemia may partly explain the link between MA and increased risk of
cardiovascular disease.
PMID- 9648081
TI - Effect of hyperparathyroidism on arterial distensibility in renal transplant
recipients.
AB - BACKGROUND: The cushioning function of the arterial system is altered in patients
with end-stage renal failure. The role of hyperparathyroidism for the altered
vessel wall properties of large arteries not known. METHODS: To exclude the
confounding effects of fluid volume changes and hypercirculation as well as
uremic toxicity on vessel wall properties from those of hyperparathyroidism, the
present study was conducted in 54 normotensive renal transplant recipients with
good graft function, three to six months after transplantation. The vessel wall
properties of the common carotid artery were investigated in 32 of them, who had
increased plasma intact parathyroid hormone (iPTH) levels (136 +/- 12 ng/liter,
SEM), and compared to those of 22 control recipients of same age with normal
plasma iPTH levels (34 +/- 4 ng/liter). Arterial distension was measured by
Doppler analysis of the vessel wall movements, blood pressure was determined by
sphygmomanometry. RESULTS: Blood pressure was 140 +/- 3/85 +/- 2 mm Hg in renal
transplant recipients with hyperparathyroidism, 135 +/- 3/83 +/- 1 mm Hg in
patients with normal plasma iPTH levels (NS). There was no difference in
enddiastolic diameter of the common carotid artery (7.4 +/- 0.2 mm) in renal
transplant recipients with hyperparathyroidism as compared with the control
patients (7.3 +/- 0.2 mm; NS). Renal transplant recipients with
hyperparathyroidism had a lower distension (389 +/- 27 microns vs. 486 +/- 28
microns, P < 0.05) and distensibility coefficient of the common carotid artery
(15.1 +/- 1.1 10(-3)/kPa vs. DC 19.0 +/- 1.0 10(-3)/kPa, P < 0.001) when compared
with the control patients. Multiple regression analysis showed that the
distensibility coefficient of the common carotid artery was negatively correlated
with age (P < 0.001), mean arterial blood pressure (P < 0.05) and plasma iPTH
levels (P < 0.05). The effects of plasma iPTH levels were not related to serum
calcium concentrations or to differences in the enddiastolic diameter of the
common carotid artery. CONCLUSIONS: The data suggest that secondary
hyperparathyroidism can affect the cushioning function of larger arteries in
patients with end-stage renal failure independently of high blood pressure.
PMID- 9648082
TI - Cyclosporine suppresses rat hepatic cytochrome P450 in a time-dependent manner.
AB - BACKGROUND: Cyclosporine is a potent immunosuppressant know to selectively
suppress specific cytochrome P450 (P450) isoforms following chronic therapy in
the rat. Cyclosporine undergoes significant hepatic metabolism in the rat,
primarily due to P450 3A isoforms. Hence, alterations in hepatic metabolism of
cyclosporine may lead to changes in drug pharmacokinetics or pharmacodynamics.
The purpose of this study was to examine the temporal effect of chronic
cyclosporine dosing on P450 protein expression and metabolic activity in a rat
model of chronic cyclosporine nephropathy. METHODS: Adult male rats were
administered cyclosporine 15 mg/kg/day or vehicle 1 ml/kg/day by subcutaneous
injection for up to 28 days. To examine whether or not metabolic activity
recovered following drug removal, additional rats were administered cyclosporine
for 28 days followed by vehicle for up to an additional 15 days. Hepatic P450
protein expression and microsomal metabolic activity were measured by Western
blot analysis and in vitro steroid hydroxylation, respectively. RESULTS:
Cyclosporine trough levels progressively increased over the 28 days period and
were still measurable for up to 15 days after discontinuation. Immunoblot
analysis indicated that chronic cyclosporine treatment suppressed P450 3A2
expression and in vitro steroid hydroxylation in a time-dependent manner. Fifteen
days following discontinuation of cyclosporine dosing, hepatic metabolic activity
and microsomal P450 3A2 levels returned to near pre-dosing levels. CONCLUSIONS:
We conclude that the time-dependent P450 suppression by cyclosporine may at least
partially explain the variability in cyclosporine pharmacokinetics. These studies
support the hypothesis that hepatic isoforms other than P450 3A2 may be
responsible for cyclosporine metabolism during chronic treatment in the rat.
PMID- 9648083
TI - Effect of alternative peritoneal dialysis solutions on cell viability,
apoptosis/necrosis and cytokine expression in human monocytes.
AB - BACKGROUND: Cellular function, cell viability and the cytokine network of human
monocytes are influenced by the specific composition of peritoneal dialysis (PD)
fluids. In an in vitro study using isolated human blood monocytes, we
investigated the effect of peritoneal dialysates containing amino acids (Amino)
or glucose polymer (Glu-poly) instead of glucose (Glu) as the osmotic agent, and
bicarbonate (Bic) or PBS instead of lactate (Lac) as a buffer. METHODS: The
following parameters were studied: mitochondrial dehydrogenase activity (using
the MTT assay), interleukin (IL)-6 and IL-8 release (ELISA) and cellular IL-6
mRNA expression after lipopolysaccharide (LPS) stimulation (using RT-PCR). FACS
flow cytometry with annexin V and propidium iodide as markers and fluorescence
microscopic methods were used to study the effects of the test fluids on cell
necrosis and apoptosis. RESULTS: Glu/Lac pH 5.5 and Glu-poly/PBS pH 7.4 both
significantly reduced mitochondrial dehydrogenase activity by more than 50% after
60 minutes of incubation (30.5 +/- 7.6%, 42.5 +/- 6.5%, referred to RPMI 1640 as
100%). Amino/Bic and Glu/Bic were both superior (Mtt assay > 63%). The rate of
necrotic cells after 15 minutes of incubation measured by FACS was mostly
increased with Glu/Lac pH 5.5 (29.9 +/- 4.0%). The rate of apoptotic cells,
however, was not significantly different between the test solutions. The
concentration of IL-6 in the supernatant of stimulated monocytes was highest with
Glu/Bic (1023 +/- 278 pg/ml) and Amino/Bic (776 +/- 296 pg/ml) an lowest with
Glu/lac pH 5.5 (46 +/- 22 pg/ml) and Glu-poly/PBS (32 +/- 13 pg/ml). IL-8 release
from stimulated monocytes showed a similar pattern. Glu-poly/PBS showed a
suppressive effect on IL-6 mRNA expression (ratio IL-6/beta-Actin, 0.4 +/- 0.25
vs. RPMI 1.5 +/- 3.6). CONCLUSIONS: Bicarbonate buffered solutions both with
glucose or amino acids as osmotic agents were superior when regarding cell
metabolism, viability and cytokine release, while lactate buffered solutions and
Glu-poly/PBS showed some reduced biocompatibility pattern for monocytes in vitro.
PMID- 9648084
TI - Immunologic function and survival in hemodialysis patients.
AB - BACKGROUND: Although the medical determinants of mortality in patients with end
stage renal disease (ESRD) treated with hemodialysis (HD) are well appreciated,
the contribution of immunologic parameters to survival in such patients is
unclear, especially when variations in age, medical comorbidity and nutrition are
controlled. In addition, although dysregulation of cytokine metabolism has been
appreciated in patients with ESRD, the association of these parameters with
outcomes has not been established. Recently, the type of dialyzer used in
patients' treatment has been associated with survival, but the mechanisms
underlying these findings, including their immune effects, have not been
established. We conducted a prospective, cross-sectional, observational
multicenter study of urban HD patients to determine the contribution of
immunological factors to patient survival. We hypothesized increased
proinflammatory cytokines would be associated with increased mortality, and that
improved immune function would be associated with survival. METHODS: Patients
were assessed using demographic and anthropometric indices, Kt/V, protein
catabolic rate (PCR) and immunologic variables including circulating cytokine
[interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-12, IL-13 and tumor necrosis
factor (TNF)-alpha] levels, total hemolytic complement activity (CH50), and T
cell number and function. A severity index, previously demonstrated to be a
mortality marker, was used to grade medical comorbidity. A Cox proportional
hazards model, controlling for patients' age, severity index, level of serum
albumin concentration, dialyzer type and dialysis site was used to asses relative
survival risk. RESULTS: Two hundred and thirty patients entered the study. The
mean (+/- SD) age of the population was 54.4 +/- 14.2 years, mean serum albumin
concentration was 3.86 +/- 0.47 g/dl, mean PCR was 1.1 +/- 0.28 g/kg/day, and
mean Kt/V 1.2 +/- 0.3. Patients' serum albumin concentration was correlated with
levels of Kt/V and PCR, and their circulating IL-13 and TNF-alpha levels, but
negatively with their circulating IL-2 levels, T-cell number and T-cell antigen
recall function. T-cell antigen recall function correlated negatively with PCR,
but not Kt/V. There was no correlation of any other immune parameter and medical
or demographic factor. Immune parameters, were all highly intercorrelated. Mean
level of circulating cytokines in HD patients were in all cases greater than
those of a normal control group. There were few differences in medical risk
factors or immune parameters between patients treated with different types of
dialyzers. After an almost three-year mean follow-up period, increased IL-1, TNF
alpha, IL-6, and IL-13 levels were significantly associated with increased
relative mortality risk, while higher levels of IL-2, IL-4, IL-5, IL-12, T-cell
number and function, and CH50 were associated with improved survival. The
difference in survival between patients treated with unmodified cellulose
dialyzers and modified or synthetic dialyzers approached the level of statistical
significance, but there were no differences in levels of circulating cytokines
between these two groups. CONCLUSIONS: Higher levels of circulating
proinflammatory cytokines are associated with mortality, while immune parameters
reflecting improved T-cell function are associated with survival in ESRD patients
treated with HD, independent of other medical risk factors. These factors may
serve as markers for outcome. The mechanism underlying the relationship of immune
function and survival, and the effect of interventions to normalize immune
function in HD patients should be studied.
PMID- 9648085
TI - Psychosocial factors, behavioral compliance and survival in urban hemodialysis
patients.
AB - BACKGROUND: The medical risk factors associated with increased mortality in
hemodialysis (HD) patients are well known, but the psychosocial factors that may
affect outcome have not been clearly defined. Psychosocial factors could affect
mortality through interaction with parents' nutrition or their compliance with
the dialysis prescription. We conducted a prospective, longitudinal, multicenter
study of urban HD patients to determine the contribution of compliance and
psychosocial factors to patient survival. METHODS: Patients were assessed using
indices of social support, patient's assessments of their well-being, including
illness effects (IEQ), and satisfaction with life (SWLS), the Beck Depression
Inventory (BDI), serum albumin concentration, Kt/V and protein catabolic rate
(PCR). Behavioral compliance was measured three ways: percent time actually
dialyzed per treatment compared to prescribed time (shortening behavior); percent
sessions attended (skipping behavior) and total integrated time compliance (%
TCOMP). A severity index, previously demonstrated to be a mortality marker, was
used to grade medical comorbidity. The typed of dialyzer the patient was treated
with was noted. A Cox proportional hazards model, controlling for age, medical
comorbidity, albumin concentration and dialyzer type was used to assess relative
mortality risk of variations in psychosocial factors and behavioral compliance.
RESULTS: A total of 295 patients (60.8% of those eligible) agreed to participate.
The mean ( +/- SD) age of our population was 54.6 +/- 14.1 year, mean PCR was
1.06 +/- 0.27 g/kg/day, and mean Kt/V 1.2 +/- 0.4, suggesting the patients were
well nourished and adequately dialyzed. The patients' mean BDI was 11.4 +/- 8.1
(in the range of mild depression). Patients' SWLS was similar to that of a group
of patients without chronic illness. After a 26 month mean follow-up period,
higher levels of perceived social support, improved perception of the effects of
illness and increased behavioral compliance were significantly associated with
decreased relative mortality risk (0.8, 0.77, and 0.79, respectively), controlled
for variations in patients' age, severity of illness, serum albumin concentration
and dialyzer type. Variations in depression and Kt/V were not predictors of
mortality during the observation period. CONCLUSIONS: Lower levels of social
support, decreased behavioral compliance with the dialysis prescription, and
increased negative perception of the effects of illness are independently
associated with increased mortality in ESRD patients treated with HD. The effects
are of the same order of magnitude as medical risk factors. Such effects may be
attributable to a relationship between a patients' perception of social support
and effects of illness and behavior, with other factors such as the provision of
better medical care in patients with larger social networks. The mechanism
underlying the relationship of psychosocial factors and compliance and survival,
and the effect of interventions to improve perception of illness, and increase
social support and compliance with the dialysis prescription in HD patients
should be studied.
PMID- 9648086
TI - Diagnostic accuracy and prognostic value of combined dipyridamole-exercise
thallium imaging in hemodialysis patients.
AB - BACKGROUND: Non-invasive detection of coronary artery disease in dialysis
patients, a major cause of mortality, often remains difficult. The aim of the
study was to test the diagnostic and prognostic accuracies of combined
dipyridamole-exercise thallium imaging in dialysis patients. METHODS:
Dipyridamole-exercise thallium imaging and coronary angiography were both
performed prospectively in 60 asymptomatic hemodialysis patients who were
followed up, long term, by recording any major coronary event. RESULTS: Coronary
angiography was abnormal in 13 patients (21%), and there was abnormal thallium
uptake in 17 patients. Sensitivity, specificity, positive and negative predictive
values, and overall accuracy of thallium to detect a coronary artery disease were
92, 89, 71, 98 and 90%, respectively. After a median follow-up of 2.8 years, 12
patients experienced at least one major coronary event (4 cardiac deaths, 5
myocardial infarctions and 3 revascularizations). Eight of the 17 patients with
abnormal thallium uptake (47%) suffered a coronary event, compared to only 4 of
the 43 patients (9%) with a normal thallium uptake (P < 0.001). The positive
prognostic predictive value of thallium imaging was 47% and its negative
predictive value was 91%. The probability of survival free of coronary events was
significantly higher in patients with normal thallium uptake than in those with
abnormal thallium uptake (crude risk ratio 7.6; P < 0.001) even after adjustment
for several risk factors for cardiovascular disease (adjusted risk ratio 9.2; P <
0.005). CONCLUSION: In dialysis patients, combined dipyridamole-exercise thallium
imaging is an accurate method for detecting coronary stenosis and for predicting
future coronary events.
PMID- 9648087
TI - On-line assessment of delivered dialysis dose.
AB - BACKGROUND: The adequacy of the delivered dialysis dose is essential to prevent
patient morbidity and mortality. The determination of effective ionic dialysance
(D) is easy, non-invasive and inexpensive, and its use instead of effective urea
clearance (K) in kinetically determining apparent" urea distribution volume (Vt)
is likely to lead to a correct Kt/V, even though the Vt value may be incorrect.
The aim of this study was to test the possibility of using the measurement of D
to monitor Kt/V on-line during each dialysis treatment. METHODS: Forty-four
patients were dialyzed using a monitor equipped with specially designed "Diascan
Module" (COT; Hospal) that measures effective D by means of a single conductivity
probe. Vt was calculated according to the SPVV three BUN method urea kinetic
model using D instead of K values. One month later, Kt/V was calculated as Dt/V,
using actual D and T values and the predetermined Vt values updated for the
current final body wt. Both the Dt/V and Kt/V determined according to the Smye
and Daugirdas methods were compared with the Kt/V determined using the SPVV
kinetic model (Kt/Veq) RESULTS: The Kt/V values calculated using ionic dialysance
and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/-
0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined
according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17,
mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). CONCLUSION: Once
Vt has been determined, the evaluation of ionic dialysance in stable patients
makes it possible to calculate the Kt/V accurately at each dialysis session
without blood or dialysate sampling, and at no additional cost.
PMID- 9648088
TI - The acu-men: a new device for continuous renal replacement therapy in acute renal
failure.
AB - BACKGROUND: We sought to design a simple machine to safely provide continuous
veno-venous hemofiltration to acute renal failure patients. RESULTS: The acu-men
device uses a pneumatic blood pump with tidal blood flow as the driving force. A
volumetric balancing system balances the filtrate with the replacement fluid, and
the blood-air interface is eliminated by replacing the conventional venous drip
chamber with two air-separating membranes. The extracorporeal circuit is
integrated in a disposable cartridge, which is inserted into the machine at the
beginning of treatment. The priming and rinsing is done automatically.
CONCLUSION: While preliminary data from an ongoing clinic trial on the efficacy
of the device are encouraging, further long-term studies are necessary to
evaluate its potential to decrease morbidity and mortality in acute renal failure
patients.
PMID- 9648089
TI - A simple procedure for the isolation of rat kidney lysosomes.
AB - BACKGROUND: A procedure for the isolation of highly purified lysosomes from
normal rat kidney is described. METHODS: The method depends on the swelling of
mitochondria when the postnuclear supernatant fraction is incubated with 2 mM
Ca2+. The lysosomes can then be separated from the swollen mitochondria by
Percoll density gradient centrifugation. RESULTS: The lysosomal fraction obtained
by our method was enriched more than 30-fold in terms of marker enzymes with a
yield of about 11%. Electron microscopic examination and the measurement of the
activities of marker enzymes for various subcellular organelles indicated that
our lysosomal preparation was essentially free from contamination by other
organelles. CONCLUSION: We believe that this procedure for isolating kidney
lysosome will be useful in the study of the mechanisms of specific modification,
processing and catabolism of proteins.
PMID- 9648090
TI - Mutational analysis of patients with cystinuria detected by a genetic screening
network: powerful tools in understanding the several forms of the disorder.
PMID- 9648091
TI - From microalbuminuria to hyperhomocysteinemia.
PMID- 9648092
TI - Dialysis fluids and monocytes: suicide or murder?
PMID- 9648093
TI - Obstructive nephropathy.
PMID- 9648095
TI - Does occupational exposure to toxins increase albumin excretion rate?
PMID- 9648094
TI - Re: Kitamura et al: "Inhibition of myo-inositol transport causes acute renal
failure with selective medullary injury in the rat".
PMID- 9648096
TI - Animal cell culture equipment and techniques.
PMID- 9648097
TI - Making informed choices: medium, serum, and serum-free medium. How to choose the
appropriate medium and culture system for the model you wish to create.
AB - Complex nutrient mixtures, which are usually called "media," are almost always
supplemented with serum, with another complex biological fluid (e.g., milk,
embryo extracts, and plasma), or with a defined mixture of hormones and growth
factors. The choice of medium and supplements can have a major impact on the
growth, function, and even phenotypic and genetic stability of cells in vitro.
This choice thus becomes an important part of developing a useful and meaningful
in vitro model system. This chapter defines the various roles that the medium
plays in supporting cell function and outlines a method for selecting and
optimizing medium in growing the cell of choice.
PMID- 9648098
TI - Cell line availability: where to get the cell lines you need.
AB - The availability and utility of cell lines with limited and continuous doubling
potential are summarized and documented. Reference to national cell banks is
included with pertinent and current contact information. The continuing need for
vigorous application of quality control procedures is emphasized with data
illustrating frequencies of microbial infection in cultured cell lines as well as
high incidences of cross-contamination of one cell line with another.
PMID- 9648099
TI - Cell culture contamination: sources, consequences, prevention, and elimination.
AB - The subject of the chapter is cell culture contamination. Contamination may enter
the cell culture system as a physical, chemical, and/or biological component of
the environment. The potential sources and consequences of cell culture
contamination are unique to the cell culture system and the contaminant. A basic
understanding of cell culture contamination is necessary to appreciate the need
to develop and practice standardized cell culture procedures. General sources,
consequences, and preventative measures are discussed for physical and chemical
contamination based on current technology. Mycoplasmal contamination is the focus
of the discussion on biological contamination and its impact on cell cultures.
The introduction of other biological contaminants should be controlled by the
institution of cell culture management procedures needed to minimize the
incidence of mycoplasmal contamination. The need to eliminate the routine use of
antibiotics in cell culture systems and institute routine testing to detect
contamination is emphasized. More rapid detection of contamination should reduce
the incidence of cross-contamination and minimize the consequences of any
contamination event.
PMID- 9648100
TI - Immortalization by gene transfection.
AB - Cultured cell lines that maintain specific differentiated phenotypes have been
indispensable tools in cell biology. Progress in understanding the function of
differentiated cells in vivo can be facilitated by creating cell lines via
immortalizing gene transduction, if they retain the essential differentiated
features of the same cells in vivo. Rodent cells immortalize spontaneously with a
frequency of 10(-5) to 10(-6). Thus, it is easy to isolate immortal cells from
rodent cell populations even without the transfer of immortalizing genes.
Immortalizing genes can be used to increase this frequency to approximately 100%.
In contrast, the spontaneous immortalization of human cells is a very rare event;
the frequency is thought to be < 10(-12). Immortalizing genes can also be used to
increase this frequency. Several genes that promise efficient immortalization of
cultured cells have been identified. Immortalizing genes include simian virus 40
large T antigen, papillomaviruses E6 and E7, adenovirus E1A, Epstein-Barr virus,
human T-cell leukemia virus, herpesvirus saimiri, oncogenes, and mutant p53 gene.
Equally important, innovative means of gene delivery have been developed as well.
These immortalizing genes, together with gene transfer methodologies, have
provided the means to generate cell lines from cell types that are not abundant
or are difficult to obtain in pure form in primary culture, are in short supply
as human cells, and/or have brief lifetimes in culture. This chapter focuses
primarily on the immortalization method by gene transfection. The chapter is not
meant to be comprehensive, but rather to provide an account of the power and
usefulness of immortalization methodology.
PMID- 9648101
TI - Establishment of mammalian testicular cell lines.
PMID- 9648102
TI - Cell hybridization, hybridomas, and human hybridomas.
AB - Cell hybridization is one of the most basic cytotechnologies. The
hemagglutinating virus of Japan was first used to cause cell fusion; however,
polyethylene glycol is widely used now because of simplicity of procedure. This
chapter first explains the principles of cell hybridization methods and then
describes the practical protocols for preparing mouse hybridomas using
polyethylene glycol. So far, lack of an excellent human fusion partner cell line
that has high fusion efficiencies and does not produce immunoglobulin has
hindered the spread of human-human hybridoma preparation methods. In the authors'
laboratory NAT-30 and HO-323, human parent cell lines with high fusion
efficiencies, have been established to prepare many hybridoma cell lines
producing cancer-specific human monoclonal antibodies. Because NAT-30 and HO-323
cell lines are IgM producers, it is difficult to obtain IgG-producing hybridomas
because the types of immunoglobulin produced by hybridomas are strongly affected
by the characteristics of parent cells. Thus a nonimmunoglobulin-producing human
parent cell line, A4H12, derived from human T lymphoma was established that can
efficiently obtain IgG-producing human hybridomas. Another problem with preparing
human hybridomas is that it is difficult to obtain B lymphocytes immunized with
optional antigens for ethical reasons. To overcome this problem, in vitro
immunization methods have been developed that allow exposure of a large number of
B lymphocytes to cultured cancer cell or soluble antigens. The section on human
hybridomas explains human fusion partners, in vitro immunization methods, and the
preparation of human-human hybridomas using an electrofusion method. Finally, the
application of human monoclonal antibodies to medical uses and the preparation of
supranatural monoclonal antibodies are reviewed. These include multifunctional
monoclonal antibodies and altered monoclonal antibodies having increased affinity
and specificity by exchanging or modifying light chains.
PMID- 9648103
TI - Establishing human glioma-derived cell lines.
PMID- 9648104
TI - Culture methods for selective growth of normal rat and human Schwann cells.
AB - Beginning with an introduction of the Schwann cell itself, this chapter provides
detailed methodology for growing pure Schwann cells of rat and human origin in
serum-free medium without complicated cell purification schemes. Section II lists
the essential preexperiment preparations such as materials, instruments, tissue
culture medium, and solutions. Section III begins with the procedure for the
dissection of embryonic dorsal root ganglia (DRG) from E14-E15 rat embryos,
neonatal rats, and adult rats with diagrams; methods for enzymatic dissociation
of the DRGs and the initiation of primary culture follow. A description of
primary cultures with photographs is also provided for comparison. This section
ends with a protocol for and results expected of serial passaging of rat Schwann
cells. Section IV carefully describes the culture of Schwann cells from human
adult nerve biopsy, a procedure that produces a thousandfold expansion of human
Schwann cells within a month from initial plating. In the last section, basic
immunocytochemistry as well as advanced in vitro remyelination techniques are
provided for biochemical and functional characterization of Schwann cell
cultures.
PMID- 9648105
TI - Invertebrate cell culture considerations: insects, ticks, shellfish, and worms.
AB - Establishment of cell lines from insect and arachnid invertebrates has become
routine, whereas other invertebrate taxa have been frustratingly unproductive of
cell lines. None is available for any marine invertebrate, despite a strong and
well-recognized need for cell lines from species that are important in
aquaculture, from parasite vectors and intermediate hosts of parasites, from
parasites themselves, from certain biomedical models, and from other species that
are pests. Drawing on experiences gained attempting to establish cell lines from
molluscs and trematodes and on published and ongoing research with diverse
invertebrates, this chapter attempts to anticipate the problems that are likely
to be encountered in such endeavors and discusses possible solutions. Criteria to
be considered in the selection of basic culture media, temperature, pH, and media
additives; approaches that have been developed to yield sterile primary cultures;
and factors to consider in decisions about feeding schedules, retention of tissue
fragments and nonadherent cells, use of heterologous feeder layers, and other
variables are described. Suggestions are made concerning means to objectively
score the success of tested variables and means to induce cell replication. The
chapter ends with notes on conventional means to characterize cell lines and an
account of contemporary efforts to immortalize cells by means of genome
manipulation. Enduring success with a single molluscan cell line, transient
successes with crustacean and helminth cell lines, and promising developments in
transgenesis with invertebrates all lead to the hopeful conclusion that the
invisible barrier to cell propagation in historically refractory species will
soon be a thing of the past.
PMID- 9648106
TI - Cell line characterization and authentication.
AB - Research and development involving the use of cell lines require precise
knowledge of the purity and species of origin of the cell lines used. This can
only be assured by periodic monitoring of cultured cell lines for possible
contamination by other cells and for characteristics that authenticate the cell
line identity. In the absence of such monitoring, inter- and intraspecies cell
line contaminations are likely to occur in the laboratories of unsuspecting
investigators and can result in the generation of mistaken conclusions with an
attendant loss of investigators' time, effort, and resources. This chapter
provides a history and an overview of the methods that have been developed for
cell line authentication, the type of information each of these different methods
provides, and how synthesis of that information can be used to characterize a
cell line and confirm its identity. An effective cell line monitoring strategy is
described that involves testing for a combination of genetic markers, including
cell membrane species antigens, isoenzymes, chromosomes, and DNA fingerprints,
and use of databases for each marker system to compare the results obtained with
a test cell culture with results from an extensive panel of previously tested
cell lines.
PMID- 9648107
TI - Laboratory scaleup of cell cultures (0.5-50 liters).
AB - With the modern tools of molecular and cell biology now available, many
researchers find the need to scale up cell culture in order to produce large
quantities of cells or conditioned medium for the further purification of
proteins or subcellular fractions. The method used for scaleup will depend on the
properties of the cell being used, the amount of material desired, the number of
times the process is to be run, and the resources available. Roller bottles,
microcarrier cultures, and hollow fiber cultures provide appropriate and
scaleable growth systems for attachment-dependent cells. However, the most
efficient production of material, especially if the large-scale production is to
be repeated several times, is obtained by suspension adapting the cells and
growing them in suspension. This can be done in spinners or in fermenters, which
range in size from 0.1 to 12,000 liters in volume. This chapter describes methods
for choosing the optimal production system and medium for scaling up to different
levels of production and for suspension adapting cells for scaleup of suspension
culture.
PMID- 9648108
TI - Cell synchronization.
AB - This chapter describes methods for analyzing the cell cycle kinetics of
asynchronous mammalian cells and for preparing synchronous cultures. The
described asynchronous cell methods include determination of mean generation time
and proliferative fraction, determination of mitotic and [3H]thymidine-labeling
indices, and estimation of cell cycle phase durations by the labeled mitoses
procedure and by flow cytometry. The described synchronization methods include
release from G0 arrest, release from M-phase and S-phase blocking agents, mitotic
detachment, and centrifugal elutriation. Caveats in interpreting cell synchrony
experiments are discussed.
PMID- 9648109
TI - Measurement of cell death.
AB - Apoptosis, or programmed cell death, is a physiological form of cell death that
plays a critical role in the development and maintenance of multicellular
organisms. Apoptosis is characterized based on morphological and biochemical
criteria. Morphological characteristics include cell shrinkage, cytoplasmic
condensation, chromatin segregation and condensation, membrane blebbing, and the
formation of membrane-bound apoptotic bodies, whereas the biochemical hallmark of
apoptosis is internucleosomal DNA cleavage into oligonucleosome-length fragments.
A great deal of research is aimed at defining the molecular mechanisms that play
a role in apoptosis. As one of the common end points of experiments related to
apoptosis is in fact the death of the cell, it has become important to develop
reliable assays to measure cell death that may be compared among the various
systems being investigated. This chapter reviews many of the current methods used
to measure apoptotic cell death and points out strengths and weaknesses of each
approach with respect to the system being examined and the questions being asked.
Traditional cell-based methods, including light and electron microscopy, vital
dyes, and nuclear stains, are described. Biochemical methods such as DNA
laddering, lactate dehydrogenase enzyme release, and MTT/XTT enzyme activity are
described as well. Additionally, terminal deoxynucleotidyl transferase-mediated
dUTP-biotin nick end labeling of DNA fragments (TUNEL) and in situ end labeling
(ISEL) techniques are reviewed, which when used in conjunction with standard flow
cytometric staining methods may yield informative data relating cell death to
various cellular parameters, including cell cycle and cell phenotype. The use of
one or more of the methods described in this chapter for measuring cell death
should enable investigators to accurately assess apoptosis in the context of the
various models being examined and help define causal relationships between the
mechanisms that regulate apoptosis and the cell death event itself.
PMID- 9648110
TI - Simultaneous measurement of cell cycle and apoptotic cell death.
AB - Understanding the dynamics of cell death in conjunction with those of cell cycle
can be illuminating in the investigation of various cellular behaviors. Robust
assays for measuring such parameters are invaluable. Many assays of apoptosis
and/or cell cycle use flow cytometry. This chapter describes two different assays
to measure apoptosis and cell cycle simultaneously using flow cytometry. The
first involves the use of terminal transferase (the "TUNEL" assay) together with
propidium iodide for identification of cell cycle. The second uses fluorescently
labeled annexin V, together with propidium iodide as an indicator of cell
membrane integrity; and additionally Hoechst 33342 for determination of cell
cycle. Each assay has positive and negative attributes. The terminal transferase
assay is performed using fixed cells and is therefore useful in the analysis of
samples collected over time. The annexin V assay is performed using unfixed
cells, and thus provides information regarding membrane integrity. Other
practical aspects of both assays are discussed.
PMID- 9648111
TI - Embryonic stem cells, creating transgenic animals.
AB - Embryonic stem (ES) cells have afforded a means of directly modifying the mouse
genome in vitro and then introducing such changes directly into animals. The
advent of this technology has made the mouse the mammal of choice for mutagenesis
approaches used in the study of embryonic development and disease conditions.
This chapter deals with the maintenance and modification of these pluripotent
cell lines and describes the routes that can be taken for their efficient
introduction to the in vivo environment.
PMID- 9648112
TI - Electron microscopy: use of transmission and scanning electron microscopy to
study cells in culture.
AB - Standard techniques for electron microscopy were developed for tissues dissected
from animals. Optimal methods for electron microscopy of cells in culture are
different. This chapter describes methods for processing cells grown on plastic
or in suspension. Both transmission and scanning electron microscopy are
discussed. The focus is on the procedures for fixation, dehydration, embedding,
and staining, which will help the reader to obtain superior electron micrographs
of cultured cells.
PMID- 9648113
TI - Indirect immunofluorescence microscopy in cultured cells.
AB - The technique of fluorescence immunolocalization has evolved steadily since its
first application in the mid-1960s, incorporating innovations in probe chemistry,
microscopy, and image detection. This chapter provides an overview of the current
status of indirect immunofluorescence for those starting to use the method. It
includes both general considerations from cell culture to image detection and
several protocols that should serve as an entry point for this technique.
PMID- 9648114
TI - Cellular localization of mRNA and protein: in situ hybridization histochemistry
and in situ ligand binding.
AB - Powerful methods for the detection of mRNA and proteins in cells and tissue
sections have been developed since the mid-1980s. This chapter discusses the
applications of in situ hybridization histochemistry and in situ ligand binding
to cells in culture and tissue sections. In situ hybridization takes advantage of
paired nucleotide interactions between a labeled probe (antisense strand) and the
endogenous mRNA (sense strand). Following processing, the mRNA is localized
through detection of the disintegration pattern of the radiolabeled probe.
Protein-protein interaction is detected in a similar fashion. Proteins are
radiolabeled and incubated with tissues that contain target-binding proteins or
receptors. On processing, the interaction sites are localized through detection
of the radiolabeled probe. The methods are rapid, sensitive, specific, and
provide important information regarding the sites of mRNA synthesis, abundance of
protein, and the ability of the ligand to interact with the receptor in
restricted cellular populations. Application of these techniques to cells in
culture allows in vitro manipulation of endogenous mRNA or protein with various
hormones or growth factors and a method to detect the results.
PMID- 9648115
TI - Epidemic neuropathy in Cuba: a public health problem related to the Cuban
Democracy Act of the United States.
AB - In 1992, the USA embargo on Cuba was tightened through the passage of the Cuban
Democracy Act (CDA) that explicitly restricts food and medical supplies. The
embargo has contributed to cause a number of public health problems in Cuba
including: (1) an epidemic of more than 50,000 cases of optic and peripheral
neuropathies in 1992-1993, resulting from dietary deficiency; (2) an epidemic of
esophageal stenoses in toddlers who inadvertently drank liquid lye as a result of
a soap shortage for which liquid lye was substituted; (3) an outbreak of Guillain
Barre syndrome in Havana, in June and July 1994, resulting from water
contamination due to lack of chemicals for water treatment to eliminate
Campylobacter sp.; (4) outbreaks of self-inflicted disease and injuries caused by
rioting among Cubans detained at the US Naval base at Guantanamo Bay, and (5) a
decline in medical practice standards and public health indicators in Cuba
resulting from the enactment of the CDA, documented by the American Public Health
Association in 1993 and confirmed in March 1997 by the American Association for
World Health. Despite this evidence, the Cuban embargo remains a politically
sensitive subject in the USA, resistant to public health concerns, as evidenced
by the recent passage of the Helms-Burton Act. The public health effects of the
CDA need to be reviewed with possible revocation or at least modification.
PMID- 9648116
TI - Health-related quality of life outcomes in stroke.
PMID- 9648117
TI - Epidemiology of stroke in The Netherlands from 1972 to 1994: the end of the
decline in stroke mortality.
AB - In 1994, stroke was responsible for the death of 4,994 men and 7,601 women in the
Netherlands, corresponding to 7.5% of all deaths in men and 11.4% in women. Age
adjusted stroke mortality declined by 39% for men and by 45% for women between
1972 and 1994. However, the decline in mortality levelled off after 1987. In
contrast to mortality, age-adjusted discharge rates increased by 47% for men and
by 28% for women during the study period. The decline in mortality was equally
distributed over the age groups, while the increase in the number of hospital
admissions was more pronounced in the older age groups. The analyses by
diagnostic subgroups of stroke showed the importance of increasing diagnostic
capabilities in the hospital setting. The use of diagnostic subgroups in national
mortality data was of limited value, illustrated by the fact that 70% of all
stroke deaths in 1994 belonged to the ill-defined type of stroke.
PMID- 9648118
TI - Stroke incidence and case fatality in two populations: the Auckland Stroke Study
and the Copenhagen City Heart Study.
AB - Comparison of stroke incidence and case fatality in different parts of the world
provides information that may lead to a better understanding of the disease. In
this report we have investigated these two aspects in two large populations, one
in Auckland, New Zealand, and the other in Copenhagen, Denmark (the Copenhagen
City Heart Study, CCHS). Incidence rates of stroke are higher for men than women
in both studies. The stroke incidence rate ratios between Auckland men and CCHS
men are significantly different in most age groups, whereas in women the
incidence rates differ only in one age group. The age- and sex-adjusted incidence
rates are higher in the CCHS for both men and women as compared to the Auckland
Stroke Study. The age-adjusted incidence rate ratio is higher for men than women
in both studies: 1.29 in the Auckland Stroke Study and 1.54 in the CCHS. The 28
day case fatality is also higher in the CCHS than in Auckland and is higher for
women than men in both studies. The incidence rate of stroke and the 28-day case
fatality is higher in the CCHS as compared to the Auckland Stroke Study in both
men and women. A very high proportion of smokers in CCHS may explain some of the
differences in incidence rates in the two populations.
PMID- 9648119
TI - The epidemiology of hospital-referred head injury in northern Norway.
AB - This retrospective population-based survey describes the epidemiology of head
injury in a defined population in Northern Norway. It includes all 247 patients
with head injury referred to the University Hospital of Tromso, Norway, during
1993. Head injury was defined as physical damage to the brain or skull caused by
external force. The annual incidence rate of hospital-referred head injury was
229/100,000 population with a male preponderance of 1.7:1.0. The cause was a fall
in 62%, road traffic accident in 21% and assault in 7% of the cases. The observed
incidence rate is low despite the use of wide inclusion criteria, probably due to
a decrease in road traffic accidents. A further decrease in the number of head
injuries in our region may be achieved by preventing falls.
PMID- 9648121
TI - Multiple sclerosis and infectious childhood diseases.
AB - To examine a possible relationship between infectious diseases and multiple
sclerosis (MS) an enquiry was carried out among 606 MS patients in Switzerland.
The data concerning their infectious childhood diseases were compared with
epidemiological data for the normal Swiss population obtained from the Swiss
Federal Health Office and from the Institute of Medical Statistics. The mean age
of the MS patients was 50.7 years and the mean age at onset of multiple sclerosis
was 33.8 years, significantly earlier in women (33.2 years) than in men (35.4
years, p < 0.05). In 18.8% multiple members of the family were affected. In
comparison with persons of the control population, MS patients had measles
infection at a later age (6.4 vs. 7.5 years). The curve of the age at which
several infectious childhood diseases occurred was shifted to higher ages for MS
patients (p < 0.005) compared to normal controls for mumps (80.2% for MS vs.
64.1% for controls in the age group 5-14 years), rubella (64.3% for MS vs. 48.4%
for controls in the age group 5-14 years) and varicella (81.9% for MS vs. 39.0%
for controls in the age group 5-19 years). For pertussis, however, there were
more cases among those who later developed MS in the age group 1-9 years, which
was earlier than in controls (86.0 vs. 56.7%). These results are compatible with
the hypothesis that the risk of developing multiple sclerosis may be associated
with acquiring certain infectious childhood diseases at a later stage in
comparison to normal controls.
PMID- 9648120
TI - The prevalence of cognitive impairment among nursing home residents in Taipei,
Taiwan.
AB - A random sample of nursing home residents over 65 years of age were interviewed.
Two hundred ninety-two participants received the Short Portable Mental Status
Questionnaire. Two hundred eleven were unable to answer the questionnaire, but
their caregivers provided information about their daily activities and
performance ability. We found that 255 (50.9%) fit our criteria of cognitive
impairment and 236 (47.7%) had both impaired cognition and impaired performance
in activities of daily living. Similar to statistics in the US, the prevalence of
cognitive impairment in Taipei nursing home residents was much higher than that
observed in the community elderly and probably in Taiwan as well. Therefore,
public health care policy for cognitively impaired elderly in Taiwan should not
simply rely on data from community studies.
PMID- 9648122
TI - Factors associated with the time of presentation of acute stroke patients in an
Israeli community hospital.
AB - Recently it has been shown that effective treatment for acute stroke must be
initiated within 3-6 h from onset. In order to determine whether this is feasible
and the reasons for delayed presentation, a prospective study was conducted in a
community hospital in Israel. Of the 216 patients enrolled, 18% arrived at the
hospital within 90 min of stroke onset and 54% presented within 6 h. Important
factors associated with early presentation included major stroke (as compared to
mild stroke) and time of day of onset (afternoon as compared with nighttime).
Further efforts must be made to shorten the delay in hospital arrival of acute
stroke patients.
PMID- 9648123
TI - Increased plasma vasopressin and atrial natriuretic peptide in chronic
schizophrenic patients during abdominal surgery.
AB - Chronic schizophrenic patients are reported to develop imbalanced water
homeostasis by the pathological secretion of vasopressin and aldosterone. We
measured plasma vasopressin, aldosterone and atrial natriuretic peptide in
schizophrenic patients to elucidate the role of these hormones during a
perioperative period. Eighteen schizophrenic patients with chronic antipsychotic
drugs over 10 years and 22 as a control group who underwent elective lower
abdominal surgery were the subjects of this study. In the schizophrenic patients,
plasma aldosterone secretion was significantly inhibited, while plasma
vasopressin and atrial natriuretic peptide were significantly increased during
surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial
natriuretic peptide and plasma osmolality was obtained 60 min after skin
incision, but not before the induction of anesthesia. The findings suggest that
chronic schizophrenic patients may develop an abnormal secretion of vasopressin,
aldosterone and atrial natriuretic peptide during anesthesia.
PMID- 9648124
TI - Season of birth in psychiatry. A review.
AB - Numerous studies suggest that seasonal birth may play a pathogenic role in the
development of mental disorders. A birth excess of 10% during winter and spring
has been shown in schizophrenia. The few studies carried out on affective
disorders revealed a significant increase of births in the first quarter of the
year in bipolar disorders and major depressive disorder. Subjects with seasonal
affective disorder show a peak of births in May. Data on personality, eating and
'neurotic' disorders are less consistent. At the moment there are no data in the
literature about anxiety disorders.
PMID- 9648125
TI - Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive
compulsive disorder.
AB - To investigate immune system function in obsessive-compulsive disorder (OCD) we
measured plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1
beta (IL-1 beta) and interleukin-6 (IL-6) in 14 drug-free obsessive-compulsive
patients and 14 matched healthy controls. No significant differences were
observed between patients and controls in plasma levels of IL-1 beta and IL-6,
whereas plasma levels of TNF-alpha were significantly lower (p = 0.001) in the
former. Blood levels of prolactin did not differ between the two groups, whereas
plasma cortisol concentrations were significantly higher in patients than in
healthy subjects (p = 0.02). No significant correlation was found between immune
parameters, on the one hand, and endocrine or psychopathological measures on the
other. These results suggest that OCD is associated with a decreased production
in TNF-alpha, but normal synthesis of IL-1 beta and IL-6.
PMID- 9648126
TI - Immunological dysfunction in schizophrenia: a systematic approach.
AB - BACKGROUND: In the present study, immunological alterations were investigated as
one possible factor contributing towards the pathogenesis of schizophrenia.
Specifically cellular changes, deviating cytokine production and interfering
variables were studied in order to improve our understanding of how these factors
interact. METHOD: 44 acutely ill schizophrenics were compared with matched
healthy controls. Cell numbers were determined by flow cytometry and cytokine
production by whole blood assay and ELISA. A criss-cross technique was employed
for the assessment of interfering serum factors. RESULTS: Cell counts for
leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell
count of the schizophrenic patients were all within normal limits. The absolute
and relative monocyte counts, the number of IL-2 receptor carrying T cells and
the relative B cell count were slightly elevated. IL-2 and IFN-gamma production
were increased while IL-10 production, the sIL-2R and cortisol levels remained
unchanged. No interfering serum factors were detected. CONCLUSION: The deficient
production of TH-1 cytokines in schizophrenia is not due either to a changed
number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL
10. Serum factors in in vitro testing are not responsible for the deficient
cytokine production.
PMID- 9648127
TI - Pathological regional cerebral blood flow in opiate-dependent patients during
withdrawal: a HMPAO-SPECT study.
AB - The aims of the present study were to investigate regional cerebral blood flow
(rCBF) in heroin-dependent patients during withdrawal and to assess the relation
between these changes and duration of heroin consumption and withdrawal data. The
rCBF was measured using brain SPECT with 99mTc-HMPAO in 16 heroin-dependent
patients during heroin withdrawal. Thirteen patients received levomethadone at
the time of the SPECT scans. The images were analyzed both visually and
quantitatively. A total of 21 hypoperfused brain regions were observed in 11 of
the 16 patients. The temporal lobes were the most affected area, hypoperfusions
of the right and left temporal lobe were observed in 5 and 5 patients,
respectively. Three of the patients had a hypoperfusion of the right frontal
lobe, 2 patients showed perfusion defects in the left frontal lobe, right
parietal lobe and left parietal lobe. The results of the quantitative assessments
of the rCBF were consistent with the results of the qualitative findings. The
stepwise regression analysis showed a significant positive correlation (r = 0.54)
between the dose of levomethadone at the time of the SPECT scan and the rCBF of
the right parietal lobe. Other significant correlations between clinical data and
rCBF were not found. The present results suggest brain perfusion abnormalities
during heroin withdrawal in heroin-dependent patients, which are not due to the
conditions of withdrawal.
PMID- 9648128
TI - The influence of polypharmacological antidepressive treatment on central nervous
information processing of depressed patients: implications for fitness to drive.
AB - Antidepressive medication may cause impairment of psychomotor functioning
relevant to psychosocial adaptation and fitness to drive. This impairment seems
to be less severe by activating antidepressants (SSRI, MAOI). In clinical
settings, however, polypharmacological treatment of depressive disorders is
frequent. This study evaluates the influence of antidepressants and common
comedications on central nervous information processing concerning the ability to
drive. Inpatients (n = 44) with major depression (ICD-10) were investigated under
steady state plasma level condition. The data were recorded by the Act & React
Testsystem ART-90 and analyzed according to medication, severity of illness and
age. 88.6% of the patients failed to pass all the tests. With respect to
different groups of antidepressants, no differences in psychomotor reaction
performance were observed in polydrug treatment. The impact of these results on
the patients' fitness to drive is discussed.
PMID- 9648129
TI - Grammatical choice and affective experience in a second-language test.
AB - This study measured the affective experience of 12 subjects reading grammatically
correct and incorrect versions of 50 sentences, Questionnaire I, in their second
language (French). This was followed by a multiple choice grammar test,
Questionnaire II, using the same 50 sentences and offering the correct and
incorrect answers. Subjects tended to choose correct as well as incorrect
responses corresponding to their highest affective rating within each entry. In
all cases the subjects' behavior was higher than chance level and thus followed a
trend to maximize pleasure. This result supports the hypothesis according to
which the key to decision-making lies in the affective dimension of conscious
experience.
PMID- 9648130
TI - Pathophysiologically correlated deficits of information processing in obstructive
sleep apnea patients.
AB - In obstructive sleep apnea patients, who intermittently stop breathing at night
for some seconds, functions of vigilance and attention seem to be impaired. The
aim of our study was to investigate if nocturnal hypoxia as one possible
detrimental factor is associated with the degree of modality shift effect
expressing attention function at a very basic level of information processing.
For the first time an experimental approach was applied to examine attention
deficits in sleep apnea patients. Correlation analyses between pathophysiological
parameters and attention function revealed a stronger association for the
modality shift effect than for simple reaction times.
PMID- 9648131
TI - Prefrontal hypooxygenation during language processing assessed with near-infrared
spectroscopy.
AB - Near-infrared spectroscopy (NIRS) is a noninvasive optical method which allows in
vivo measurements of relative concentrations of oxygenated (O2Hb) and
desoxygenated hemoglobin (HHb). It has been successfully applied to assess the
blood oxygenation changes during cerebral ischemia in man. An interesting
application of NIRS is the investigation of regional cerebral blood oxygenation
during physiological brain functions. In the present study, left and right
anterior prefrontal brain areas of 10 healthy subjects were investigated with 2
channel NIRS during language processing (reading aloud). Nonverbal visual
perception (picture observation) was performed as a control condition. Compared
to the respective baseline conditions, a significant HHb increase and an O2Hb
decrease as a trend were found during language processing but not during the
nonverbal perceptual task, and no hemispheric differences were found. The
metabolic activation patterns differed significantly between the tasks indicating
the changes due to the language-related efforts but not to visual perception.
Based on previous findings of metabolic brain imaging studies the results are
best explained as a complementary phenomenon consisting in relative anterior
prefrontal hypoperfusion due to a blood volume redistribution which favors
language-related temporal areas.
PMID- 9648132
TI - Nursing: a privilege.
PMID- 9648133
TI - Is another RN shortage looming?
PMID- 9648134
TI - The changing health care market: implications for nursing education in the coming
decade.
PMID- 9648135
TI - Corporate language and nursing practice.
PMID- 9648136
TI - A middle-range theory of acute pain management: use in research.
PMID- 9648137
TI - Practice-based research networks for nursing.
PMID- 9648138
TI - Caring to confront in the workplace: an ethical perspective for nurses.
PMID- 9648139
TI - Incremental approaches to necessary health care reform lead to more chaos.
PMID- 9648140
TI - Overdrugging and undertreatment in primary health care.
PMID- 9648141
TI - ["And what we are, you will be"--on the dignity and integrity of plasticized
cadavers].
PMID- 9648142
TI - [Myofibroblastic tumors. Brief review of clinical aspects, diagnosis and
differential diagnosis].
AB - This review summarizes myofibroblastic tumours that have been characterized in
the last years. These lesions include: fibromatoses in adults and infants
(infantile digital fibromatosis and infantile myofibromatosis); myofibroma of
adults, an almost exclusively solitary lesion in the skin which is characterized
morphologically as a biphasic lesion composed of spindle-shaped eosinophilic
tumour cells and more primitive mesenchymal tumour cells associated with a
haemangiopericytoma-like vasculature; dermatomyofibroma (plaque-like dermal
fibromatosis), a band-like myofibroblastic proliferation in young female
patients, which is mainly located in the periaxillar region and in which
distinction from more aggressive, plaque-like variant of dermatofibrosarcoma
protuberans is mandatory; myofibroblastoma of the breast, a well-circumscribed
lesion composed of spindle shaped, desmin-positive tumour cells, which is seen
mainly in elderly male patients and has to be distinguished from other spindle
cell lesions of the breast; angiomyofibroblastoma, a well-circumscribed
myofibroblastic neoplasm of the vulva and vagina composed of avoid to round myoid
tumour cells with scattered multinucleated cells, which forms a continuous
morphological spectrum with the clinically more aggressive angiomyxoma in this
location; intranodal myofibroblastoma, a distinctive proliferation of
myofibroblastic cells associated with so-called amianthoid fibres, which is seen
most commonly in inguinal lymph nodes; myofibroblastoma/myofibroblastic tumour of
soft tissues, a variably well-circumscribed myofibroblastic lesion which lacks
atypia and is composed of actin and/or desmin positive tumour cells, and poorly
delineated sarcomas with myofibroblastic differentiation (myofibrosarcoma).
PMID- 9648143
TI - [Myofibroblasts. Review out outlook].
AB - When studying inflammation and wound healing, peculiar fibroblasts with
ultrastructural similarities to smooth muscle cells were described by a group of
pathologists associated with Guido Majno (GM) and Giulio Gabbiani (GG),
subsequently called myofibroblasts. Similar cells were also found later in human
granulation tissue, palmar fibromatosis and in stromal reactions with invasive
cancers. Their identification was facilitated by immunohistochemical methods.
Some neoplastic cells, for instance in MFH, also revealed characteristics
compatible with myofibroblasts. Myofibroblasts are conceived of as modulated
fibroblasts. Cytokines may serve as mediators for activation and contractile
modification of fibroblasts. In this context monitoring of a tumor-like
overproduction of myofibroblasts or an underproduction with non-union of wounds
might also be feasible. Moreover, better understanding of the role of
myofibroblasts concerning the transition from in situ carcinomas into invasive
growth may have therapeutic perspectives. Myofibroblasts apparently not only show
a temporary existence in disease, but also can be found under normal conditions
in several regions, such as the skin, periodontal ligaments, or pulmonary septa.
PMID- 9648144
TI - [Liver changes in AIDS. Retrospective analysis of 227 autopsies of HIV-positive
patients].
AB - In a retrospective study of a 12-year period (1981-1992) liver histology was
analyzed in 227 autopsied patients infected with the human immunodeficiency
virus. Normal histology could only be documented in 29 patients (13%). In the
majority of cases (56%) uncharacteristic changes were seen such as steatosis
(34%), hemosiderosis (10%) or non-specific reactive hepatitis (7%). The finding
of hepatic peliosis obtained in 4 patients was not associated with inflammatory
liver changes, especially infections from Rochalimaea. Within a wide range of
opportunistic infections recorded in 50 patients (22%), hepatitis caused by
Cytomegalovirus (8%), Toxoplasma gondii (5%), Leishmania donovani (1%),
Cryptococcus neoformans and Pneumocystis carinii (each 0.5%) was diagnosed. Among
16 cases (7%) of mycobacterial liver infections typical mycobacteria were found
in two patients and atypical mycobacteria in 14 patients, respectively. In 23
patients (10%) chronic viral hepatitis, caused by HBV (7%) or HCV infections
(3%), respectively, was observed. Hepatitis was typed as mild only in each 5
patients with HBV or HCV infection, whereas the remaining cases showed a
transition towards cirrhosis. Two patients with HBV-associated cirrhosis
developed hepatocellular carcinoma. The remaining 32 malignant liver tumors
represented secondary neoplasms, including 13 cases of non-Hodgkin's lymphomas.
PMID- 9648145
TI - [Differential diagnosis of squamous epithelial carcinoma of the salivary glands].
AB - Primary squamous cell carcinomas (SCC) of the salivary glands are localized
predominantly in the major salivary glands and must be distinguished from
metastases of extraglandular SCC of the skin, especially the head and neck area.
Squamous cell metaplasia in non-tumourous diseases of the salivary gland (e.g.
necrotizing sialometaplasia) as well as in benign or malignant salivary gland
tumours (e.g. metaplastic Warthin tumour) can simulate SCC. Other differential
diagnostic problems are the structural variants of SCC which develop
predominantly in the minor salivary glands, but not in the major salivary glands.
Special types include the very rare adenoid SCC with pseudoglandular structures
as the result of acantholysis, the biphasic adenosquamous carcinoma with
differentiation as SCC and adenocarcinoma, the biphasic basaloid squamous
carcinoma with a structure as SCC and solid basaloid carcinoma (analogous to the
solid type of adenoid-cystic carcinoma) and the poorly differentiated
mucoepidermoid carcinoma (grade III) with biphasic structure of undifferentiated
epidermoid and intermediate cells as well as inclusion of small groups of mucous
producing goblet cells. The differential diagnostic criteria are analysed
concerning prognosis and treatment.
PMID- 9648146
TI - [Diagnostic value of stomach biopsy in comparison with surgical specimen in
gastric B-cell lymphomas of the MALT type].
AB - Diagnostic und therapeutic management of gastric lymphomas of the mucosa
associated lymphoid tissue type (MALT-type lymphomas) is often based exclusively
on the evaluation of biopsy material. To evaluate the diagnostic value of gastric
biopsies in gastric MALT-type lymphomas, biopsies--on average six per patient-
and subsequent surgical specimens of 64 patients were compared at the Institute
of Pathology, University of Wurzburg. Tumor diagnosis and tumor gradind were
assessed. Using biopsy specimens, primary gastric MALT-type lymphomas were
correctly diagnosed by local pathologists in 69% of cases, but correctly graded
as low-grade, high-grade or secondary high-grade lymphomas in only 41%. When
immunohistochemistry and molecular biological techniques were applied in addition
to conventional histology, diagnosis of gastric MALT-type lymphoma was achieved
in biopsies in 95% of cases at the Institute of Pathology Wurzburg, but correct
grading in only 73%. In secondary high-grade MALT-type lymphomas, both components
-the high-grade and the low-grade component--were identified in gastric biopsies
in only 33% of cases. Diagnostic accuracy in gastric lymphomas based on biopsies
is limited by biopsy artefacts, but improved by using immunohistochemistry and
molecular biological techniques. Particularly in secondary high-grade MALT-type
lymphomas the correct diagnosis is often missed when using biopsies, due to a low
number of biopsy specimens.
PMID- 9648147
TI - [Pleural reaction pattern after talc pleurodesis].
AB - Because of the rising importance of talcum pleurodesis in the therapeutic
management of malignant and benign pleural effusions in Germany, pleural samples
after talcum pleurodesis were compared to microscopic, immunohistochemical, and
scanning electron microscopy findings after Tetracyclin and Novantron pleurodesis
in 24 patients up to 18 months after intrapleural therapy. The histomorphological
findings after talcum pleurodesis show an early phase of up to 4 weeks,
characterized by the presence of talcum-containing granulation tissue with giant
cell foreign-body reaction, and a subsequent late phase with organization of the
granulation tissue and connective tissue formation and obliteration of the pleura
sheets. The resulting characteristic linear talcum zone in the pleural connective
tissue is missing in cases with tumorous infiltration of the pleura. Continuous
fibroblast activation, e.g., by macrophage or foreign-body giant-cell-released
mediators, seems to be the decisive factor in the fibrosing process. No therapy
related tumor growth alterations could be demonstrated.
PMID- 9648148
TI - [Adult giant cell hepatitis with fatal outcome. Clinicopathologic case report and
reflections on pathogenesis].
AB - The occurrence of plasmodial giant cells in the liver is probably a morphological
reaction pattern with the most diverse causes. In babies and infants, these
changes occur in particular in neonatal hepatitis and intrahepatic and
extrahepatic bile duct atresia. Viral infections and/or autoimmune reactions are
discussed etiologically in giant cell hepatitis in adults (adult gaint cell
hepatitis, AGCH), which is much rarer. In some of the cases, there were
conspicuously high titers against paramyxoviruses. Giant cell hepatitis can occur
in the course of HIV infection. These both indicate an infectious cause. However,
the disease cannot be transmitted to chimpanzees. Apart from our case, only one
further case is described in the literature in which a completed hepatitis A
infection could be demonstrated serologically. In addition, the titer of
antinuclear antibodies was raised in our patient. This autoimmune phenomenon is
probably of crucial pathogenetic significance in our patient, especially since a
hepatitis A infection on its own does not afford an adequate etiological
explanation for the form of chronic and active hepatitis with consecutive
cirrhotic transformation observed here.
PMID- 9648149
TI - [Mesoblastic nephroma in adulthood].
AB - We report a 44-year-old female patient who underwent surgery because of a
suspected primary tumor of the renal pelvis in imaging procedures. Histology
revealed the diagnosis of mesoblastic nephroma. This tumor represents a special
entity of nephroblastoma that rarely occurs in adults. There is no unanimous
opinion on the biological behavior of mesoblastic nephroma because the tumor
behaves differently. The question of whether nephrectomy is indicated if there
are no malignant features is also open. The decision depends on the given case.
Nephrectomy can only be avoided if the intraoperative situation allows the tumor
to be removed with an adequate distance from healthy tissue. The safety margin is
necessary because mesoblastic nephroma shows fingerlike spread into the
surrounding tissue.
PMID- 9648150
TI - [Glomerulopathy in Denys-Drash syndrome. Case report of a model disease].
AB - About 10% of all nephroblastomas (Wilms' tumor) present as part of malformation
syndromes. The Denys-Drash syndrome (DDS) comprises pseudohermaphroditism,
glomerulopathy and, early, often bilateral Wilms' tumors. A nephrectomy was
performed in a 4-month-old girl because of a Wilms' tumor. Two months later, low
serum albumin levels and proteinuria had developed. A biopsy from the remaining
kidney showed a glomerulopathy which could also be seen in the nephrectomy
specimen. The morphology was highly characteristic: the innermost layer of the
kidney cortex exhibited augmentation of the mesangial matrix only; the
intermediate layer showed severe sclerosis of glomeruli with deposition of
fibrillary material; and the subcapsular layer revealed very small glomeruli and
atrophic tubuli. Fifteen months later, peritoneal dialysis was necessary and due
to the high risk of tumor development in the remaining kidney, a nephrectomy was
performed. Molecular analysis revealed a point mutation within exon 9 of the WT1
gene (394 ARG-->TRP), which was homozygous in the tumor and heterozygous within
renal parenchyma. The DDS is caused by a mutation in the WT1 gene on chromosome
11p13 which occurs during oogenesis or spermiogenesis. The WT1 gene is highly
expressed during the development of the genitalia and the kidney; damage in one
allele only causes the malformation syndrome. Loss of the second allele of the
WT1 gene constitutes the second step of tumorigenesis. The appearance of Wilms'
tumors derived from cells homozygous for the mutation reveals the function of the
WT1 gene as a tumor suppressor gene.
PMID- 9648151
TI - [Standardization of cytopathologic diagnosis].
PMID- 9648152
TI - So-called neoplastic myoepithelial cells in chondroid syringomas/mixed tumors of
the skin: their subtypes and immunohistochemical analysis.
AB - An immunohistochemical study of nine cases of chondroid syringomas/mixed tumors
of the skin was performed to elucidate the nature of the so-called neoplastic
myoepithelial cells (NMEC) in tumor tissues. These nine tumors contained NMEC of
considerable variability in number from one tumor to another. These NMEC were
classified into three types: (i) hyaline cells (plasmacytoid cells); (ii) spindle
NMEC; and (iii) polyhedral cells. They showed different immunostaining patterns,
as the following describes. Cytokeratin 14 was positive in most of the spindle
NMEC and a large number of the polyhedral cells, and in a small number of the
hyaline cells. Concerning low molecular weight cytokeratins, most of the hyaline
cells showed immunoreactivity, whereas they were negative in many of the spindle
NMEC and were expressed only in a small number of the polyhedral cells. alpha
Smooth muscle actin and muscle-specific actin were positive in the spindle NMEC
but negative in any of the hyaline cells and polyhedral cells. These findings
strongly indicate that the hyaline cells and the spindle NMEC are of the simple
epithelial and myoepithelial types, respectively. The findings also suggest that
the polyhedral cells show differentiation toward basal cells of the sweat gland
dermal ducts or myoepithelial cells.
PMID- 9648153
TI - Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of
lymph node metastasis: ultrastructural comparison between lymphatics and blood
vessels.
AB - The ultrastructural modes of lymphatic and blood vessel invasions were studied
comparatively in hamsters with squamous cell carcinoma (O-1N) that had a high
potential for lymph node metastasis. The endothelial injury, which was caused by
mechanical stretching with the growth of O-1N, was the initial and characteristic
feature common to both vascular invasions. Tumor cell nests penetrating the
lymphatic lumen through disrupted endothelial cells still maintained their volume
and continuity to the underlying tumor cell nests. In contrast, pronounced
microthrombotic and neutrophilic reactions occurred at the site of blood vessel
penetration. Within the lymphatic lumen, large clusters of O-1N cells were kept
longer in spite of lymphocytic and macrophagic reactions. In blood vessels,
clusters of tumor cells that had passed through dense fibrin layers were reduced
in size and further disintegrated into smaller pieces by neutrophils. In
conclusion, lymphatic invasion is a mechanical process, and smooth and direct
invasion of large tumor cell nests into lymphatic vessels is responsible for
causing more prompt and frequent lymph node metastasis in O-1N than a
hematogenous type.
PMID- 9648154
TI - DNA analysis at p53 locus in carcinomas arising from pleomorphic adenomas of
salivary glands: comparison of molecular study and p53 immunostaining.
AB - Where and how frequently p53 abnormalities are involved in the development of
pleomorphic adenoma (PA) and its malignant progression to carcinoma was
investigated. The presence of p53 gene abnormalities was analyzed in eight
patients with carcinoma in pleomorphic adenoma (CPA) by polymerase chain reaction
(PCR)-based assays and immunohistochemistry. Normal salivary gland tissue,
adenomatous, transitional and carcinomatous areas were microdissected from
archival microslides and analyzed for allelic deletions of the p53 gene using two
microsatellite markers at the p53 locus; dinucleotide (CA)n repeat and
pentanucleotide (AAAAT)n repeat. Loss of heterozygosity (LOH) of the p53 gene was
detected in 57% of adenomas, 86% of transitional lesions and 86% of carcinomas.
In contrast, overexpression of p53 oncoprotein was noted immunohistochemically in
13% of adenomas, 50% of transitional areas and 75% of carcinomas. All of the
tumors with immunoreactivity for p53 oncoprotein demonstrated LOH. Moreover, when
LOH was present in adenomatous or transitional areas, the identical LOH was
always detected in the corresponding carcinomatous areas in the same CPA tumors.
These findings indicate that p53 gene mutation is an early event and occurs
frequently at an early stage of precancerous lesions and may be responsible for
most cases of malignant transformation of PA.
PMID- 9648155
TI - DNA analysis at p53 locus in adenoid cystic carcinoma: comparison of molecular
study and p53 immunostaining.
AB - Abnormalities of the p53 tumor suppressor gene were investigated in 22 foci from
14 adenoid cystic carcinomas (ACC) by polymerase chain reaction (PCR)-based
assays for dinucleotide (CA)n and pentanucleotide (AAAAT)n repeat polymorphisms
and by immunohistochemical staining for oncoprotein expression. Adenoid cystic
carcinomas were divided into lower grade (tubular and cribriform) subtypes and
higher grade (trabecular and solid) subtypes. Histologically identified tumor
cells were precisely microdissected from archival microslides and were used for
molecular analysis. The overall frequency of p53 gene mutations detected by PCR
loss-of-heterozygosity (LOH) analysis was 57% and was higher than the frequency
of over-expression of p53 oncoprotein detected by immunostaining (43%). In the
molecular analysis of individual histological subtype foci, the number of foci
with p53 gene mutation was significantly greater in the higher grade subtype foci
than in the lower grade subtype foci and was greatest in solid-type foci (100%).
In all six tumors in which histologically different foci were present in the same
tumors, mutations of the p53 gene were detected. When tumor heterogeneity of the
p53 gene was present among different histological foci in the same tumors, the
mutations were always detected in the higher grade foci. When lower and higher
grade foci were present in the same tumors, the identical mutations detected in
the lower grade foci were present in the corresponding higher grade foci. These
findings indicate that abnormalities of the p53 gene are involved in
carcinogenesis and/or progression of this tumor and, furthermore, suggest that
molecular analyses of ACC may provide information of prognostic importance.
PMID- 9648156
TI - Overexpression of p53 protein correlates with a high risk of malignant
transformation of adenomas in patients with multiple colorectal adenomas.
AB - To assess the correlation of p53 oncoprotein expression with the high risk of
developing carcinomas in patients with multiple colorectal adenomas, 25 cases
with histologic carcinoma in adenoma (CIA) were examined by immunohistochemistry
using a monoclonal antibody specific to human p53 protein (wild and mutant). The
25 cases were classified into multiple and single groups. The former contained 13
cases with synchronous multiple colorectal adenomas (one to six adenomas) and
adenocarcinoma. The latter included 12 cases with single CIA only. This study
revealed an overall incidence of 57.14% of p53 overexpression in carcinomatous
lesions and 31.9% in adenomatous lesions, which was statistically significant (P
< 0.05). The carcinomatous lesions showed a diffuse staining pattern, whereas the
adenomatous lesions showed a focal pattern. A significant finding was that the
incidence of p53 overexpression was significantly higher in multiple groups
(81.25%) than in single groups (31.43%) in the carcinomatous (P < 0.01) rather
than in the adenomatous (P < 0.05) lesions. There were no correlations between
p53 overexpression and proliferation activity or carcinoembryonic antigen
expression. The results indicate that p53 abnormality may be an important genetic
factor responsible for the high risk of developing carcinomas in patients with
multiple adenomas.
PMID- 9648157
TI - Sebaceous carcinoma of the submandibular gland with high-grade malignancy: report
of a case.
AB - A case of sebaceous carcinoma arising in the left submandibular gland of a 66
year-old man is reported. The clinical and pathological examinations revealed a
carcinoma, which was to salivary gland in origin, with regional lymph nodal
metastases. Pathological findings showed features of high-grade sebaceous
carcinoma with spindle myoepitheliomatous differentiation. Neither squamous cell
nor duct epithelial-like cell differentiation was noted. Immunohistochemically,
tumor cells were positive for cytokeratin, S-100 protein and vimentin. Lipid was
demonstrated in the cytoplasm of the tumor cells. Ultrastructurally, tumor cells
contained numerous intracytoplasmic lipid droplets. Myoepitheliomatous
differentiation is rare in sebaceous carcinoma of the salivary gland. Presented
is the second reported case of sebaceous carcinoma arising in the submandibular
gland.
PMID- 9648158
TI - Angiomyofibroblastoma of the vulva: a mitotically active variant?
AB - A case of angiomyofibroblastoma in a 48-year-old woman is reported. The tumor
occurred as a left vulval mass and was treated by simple excision. It was located
in the subcutaneous tissue of the left vulva and was well circumscribed,
measuring 2.8 x 2.7 x 2.5 cm. Microscopically, the tumor was composed of
hypocellular and cellular areas with well-developed small vessels. Spindle or
polygonal cells were arranged with perivascular accentuation in an edematous or
fibrocollagenous background. Some spindle-shaped or polygonal stromal cells were
also arranged in epithelioid nests. In some areas, mitoses were frequent (maximum
3/10 high-power field). Immunohistochemically, the stromal cells were positive
for vimentin and desmin, but negative for alpha-smooth muscle actin, S-100,
neurofilament, estrogen receptor, progesterone receptor, CD31 and CD34. The
average labeling index of Ki-67 in stromal cells was 3.1%. Ultrastructural
analysis demonstrated that the stromal cells adhered with primitive junctions and
contained intermediate filaments with no focal density in the cytoplasm. These
findings were consistent with angiomyofibroblastoma, although previously reported
cases did not show so many mitoses. Therefore, this case was suggested to be a
mitotically active variant.
PMID- 9648159
TI - Extrauterine low-grade endometrial stromal sarcoma: report of three cases.
AB - Three cases of rare low-grade endometrial stromal sarcoma of the extrauterine
tissue are presented. Each one occurred in the ovary, pelvic and abdominal
cavities. Two were associated with endometriosis. Histologically, the tumors were
characterized by an infiltrative and diffuse proliferation of uniform round or
oval cells, abundant small vessels, low mitotic activity, the presence of foam
cells and vascular invasion. Immunohistochemically, all tumors expressed
vimentin, muscle markers (desmin, muscle-specific actin and alpha-smooth muscle
actin) and progesterone receptors. Two tumors were diploid and one was aneuploid
by flow cytometry. All patients were well with no evidence of disease 16-39
months after surgery. It is suggested that this neoplasm may arise with or
without endometriosis under hormonal influence. This rare variant of Mullerian
tumors should not be confused with adenosarcoma and soft tissue tumors, such as
smooth muscle tumors and solitary fibrous tumor.
PMID- 9648160
TI - Small cell carcinoma of the gall-bladder with intestinal metaplastic epithelium.
AB - A case of small cell carcinoma of the gall-bladder is described.
Immunohistochemically, the tumor cells were positive for chromogranin A,
synaptophysin and neuronspecific enolase, which suggests that they derived from
neuroendocrine cells. The overlying and surrounding epithelium of the tumor
showed intestinal metaplasia including goblet cells, pseudopyloric glands,
Paneth's cells, and chromogranin A and synaptophysin-positive endocrine cells.
Definite adenocarcinoma was absent. The endocrine cells in the epithelium were
more numerous in the vicinity of the tumor. The present case supports the
supposition that endocrine cell tumor (including small cell carcinoma) of the
gall-bladder may develop from endocrine cells of the intestinal metaplastic
lesion.
PMID- 9648161
TI - Intranodal palisaded myofibroblastoma with so-called amianthoid fibers: a report
of two cases with a review of the literature.
AB - Two cases of intranodal myofibroblastoma, a rare primary spindle cell tumor of
the lymph node, are described. The tumors arose in the inguinal or proximal
region of the thigh of one middle-aged and one elderly Japanese male. The tumors
were well-demarcated and composed of a fascicular proliferation of spindle cells
with focal nuclear palisading and acellular stellate-shaped collagen-rich areas
(so-called amianthoid fibers), and were associated with hemorrhagic areas.
Immunohistochemically, the tumor cells were positive for vimentin and muscle
actin. Together with ultrastructural findings of intracytoplasmic microfilaments
with focal densities and profiles of well-developed, rough endoplasmic reticulum,
these features reinforced the conclusion of myofibroblastic or smooth muscle
differentiation of the tumor cells. One of the tumors was analyzed by flow
cytometry and was shown to be DNA diploid. The present report provides
clinicopathological findings of the first two Japanese cases of intranodal
myofibroblastoma.
PMID- 9648162
TI - Multiple organ failure associated with extensive metastatic calcification in a
patient with an intermediate state of human T lymphotropic virus type I (HTLV-I)
infection: report of an autopsy case.
AB - A patient with an intermediate state of human T lymphotropic virus type I (HTLV
I) infection and in whom autopsy showed multiple organ failure (MOF) associated
with extensive metastatic calcification in systemic organs is described. A 56
year-old man presented with signs and symptoms of advanced cardiac insufficiency,
respiratory disturbance and renal failure. Serologically, the anti-human T
lymphotropic virus type I (HTLV-I) antibody titer and the levels of both calcium
and parathyroid hormone-related peptide (PTHrP) were distinctly elevated. These
data suggested a diagnosis of adult T cell lymphoma/leukemia (ATLL). However,
examination of a peripheral blood sample revealed only a few atypical lymphoid
cells (3%) associated with mild leukocytosis (white blood cell count, 13.7 x
10(3)/mm3). Lymph node swelling was systemic but mild, with some nodes up to 10
mm in diameter. The patient died of MOF. Adult T cell leukemia/lymphoma was
unable to be diagnosed definitively because of the short duration of laboratory
abnormalities and because of the discrepancy between the laboratory data and the
magnitude of lymphoproliferation in both the lymph nodes and peripheral blood. At
autopsy, the most conspicuous finding was extensive metastatic calcification in
the multiple organs, including the heart, lungs, kidneys, tongue, liver,
pancreas, spleen and systemic arterial walls. Very small numbers of medium-sized
atypical lymphoid cells admixed with small reactive lymphocytes were identified
in multiple organs, with no evidence of massive infiltration. Molecular analyses
could not detect monoclonal integration of HTLV-I provirus DNA or monoclonality
of T cell lineage cells. Parathyroid hormone-related peptide was demonstrated in
the cytoplasm of the atypical lymphoid cells on immunohistochemical examination.
The bone trabeculae generally showed distinct evidence of resorption associated
with marked proliferation of osteoclasts. These findings suggested that the
hypercalcemia in the present case was categorized as humoral hypercalcemia of
malignancy rather than local osteolytic hypercalcemia.
PMID- 9648163
TI - MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors
of the pancreas.
AB - The expression of MUC-1 mucin (membrane-associated mucin) and MUC-2 mucin
(secretory mucin) were immunohistochemically examined in 46 invasive ductal
carcinomas (IDC) and 16 intraductal papillary mucinous tumors (IPMT) of the
pancreas. Intraductal papillary mucinous tumors usually reveal expansive growth.
However, of the 16 IPMT examined in the present study, three showed an invasive
growth pattern, which was similar to 'mucinous carcinoma', around the non
invasive growth areas. Of 46 IDC, MUC-1 mucin detected by monoclonal antibodies,
DF3 and MY.1E12, was expressed in 44 cases (96%) and in 45 cases (98%),
respectively, whereas MUC-2 mucin detected by polyclonal antibody, anti-MRP, was
not expressed in any of the cases (0%). In contrast, in the non-invasive growth
areas of the 16 IPMT, MUC-1 mucin detected by DF3 and MY.1E12 was expressed in
four cases (25%) and in six cases (38%), respectively, whereas MUC-2 mucin
detected by anti-MRP was expressed in 13 cases (81%). The invasive growth areas
of the three IPMT showed positive expression of MUC-1 mucins detected by DF3 and
MY.1E12, although the non-invasive growth areas showed negative expression of MUC
1 mucins, except for their focal positive expression in one of the three cases.
These findings indicate that the invasive growth areas of IPMT acquire a
characteristic of MUC-1 mucin expression that is usually seen in IDC.
PMID- 9648164
TI - More on pediatric dermatology.
PMID- 9648165
TI - Immunization rates: where is the help when we need it?
PMID- 9648166
TI - When you run the zoo: the need for residents to learn strategies for delivering
childhood immunizations.
PMID- 9648167
TI - Childhood vaccination successes, yes, but the job is not finished.
PMID- 9648168
TI - 1998 immunization schedule changes and clarifications.
PMID- 9648169
TI - Immunization registries: the cornerstone of childhood immunization in the 21st
century.
PMID- 9648170
TI - Evidence on office-based interventions to improve childhood immunization
delivery.
PMID- 9648171
TI - Barriers to immunization and missed opportunities.
PMID- 9648173
TI - What is physiotherapy?
PMID- 9648172
TI - Taking the sting out of shots: control of vaccination-associated pain and adverse
reactions.
PMID- 9648174
TI - Breathing patterns and heart rate during simulated occupational upper limb tasks
in normal subjects.
AB - BACKGROUND AND PURPOSE: Despite the arms being used extensively in the
performance of many occupational tasks, little is known about the pattern of
breathing and physiological cost of such work. The purpose of this study was to
establish whether a simple change in arm support could alter the workload,
pattern of breathing and respiratory muscle recruitment during a low intensity
arm task. METHODS: Ten normal subjects performed a simulated work task when
sitting, once with the arms supported and once unsupported. Subjects were
required, over a five-minute period, to repeatedly pick up a 2 kg object, inspect
and hold it for 15 seconds and then pack it in a box. Breathing pattern
responses, measured by pneumotachograph and respiratory inductive
plethysmography, were minute ventilation (VE), respiratory frequency (Rf), tidal
volume (VT) and change in functional residual capacity (FRC). RESULTS: The main
findings were that unsupported arm work was more physiologically demanding than
supported arm work. During work VE increased as a result of a change in
respiratory frequency but not VT which was much more limited when the arms were
unsupported. At the completion of activity, when the arms were unloaded, VT
initially increased as VE decreased. FRC and VT were reduced during arm work and
increased during recovery, mainly as a result of a change in ribcage excursion.
CONCLUSIONS: These findings support the theory that during arms activity,
intercostal and accessory respiratory muscles act to stabilize the arms and
torso, impeding chest wall movement and shifting the respiratory load from these
muscles to the diaphragm. This may adversely effect performance of workers who
have ventilatory limits to arm work tasks.
PMID- 9648175
TI - Motivating factors for return to work.
AB - BACKGROUND AND PURPOSE: A new concept to increase return to work for patients
listed as sick with chronic musculoskeletal pain has been used at a
rehabilitation centre in Lulea, Sweden. The programme includes work for three
days a week and intensive rehabilitation for two days a week, for 12 weeks, as a
combination of 'on the job' training and rehabilitation after a period off work
sick. The rehabilitation programme focused on pain reduction, identifying and
finding solutions to pain problems in actual work and life situations and
training of the functional capacities needed in the work and life situation. The
aim of the study was to describe patients' perceptions of motivating factors for
return to work. METHODS: A phenomenological method was used. A naive reading of
interview notes was followed by structural analyses and reflections on the
interpreted whole. Inclusion criteria for the study were musculoskeletal pain for
at least one year and a period of at least four weeks' sick leave during that
time. Ten patients, aged 30-54 years, participated in the study. An initial
conceptual framework was developed to inform the scope of the study and to guide
data collection and analysis. RESULTS: Different factors in the study framework
influenced motivation to return to work. Among structural factors the division of
labour at work was the most important motivator, particularly the ability to do
as much as work colleagues, quantitatively and qualitatively. All the patients
had jobs in the healthcare or service sectors, jobs with many social contacts.
They perceived their work task content as being of minor importance compared to
whether the tasks were perceived as meaningful or highly needed by others. All
wanted a meaningful job content and a job which they could do in a satisfactory
way according to their own norms and compared to colleagues. This highly
increased motivation for return to work. Relationships (in terms of co-operation
with colleagues and service to patients or clients) were important motivating
factors for return to work. Self-confidence was a new factor of importance for
return to work; work tasks had to be meaningful and needed by others, work must
be done in a way satisfactory for the individual and in a way that was acceptable
to others in the group. Everyday responsibility, feedback and support in daily
work tasks were important. These aspects increased self-confidence. The results
supported the development of a new conceptual framework for possible motivating
factors for return to work. CONCLUSIONS: Structure, content, relationships,
health and self-confidence were all important motivating factors for return to
work.
PMID- 9648176
TI - Changes in balance and locomotion measures during rehabilitation following
stroke.
AB - BACKGROUND AND PURPOSE: This study aimed to examine the utility of a number of
measures of balance and locomotion for the purpose of measuring change in a group
of stroke patients undergoing in-patient rehabilitation. The aim was to select a
core group of measures based on empirical evidence of usefulness rather than
personal preference. METHODS: Twenty-nine stroke patients undergoing in-patient
rehabilitation (mean age 71.8 +/- 10.5 years; 66% male) participated in the
study. A prospective design was utilized with repeated measurement undertaken at
four, six and eight weeks post-stroke. Static standing, the Clinical Test of
Sensory Interaction of Balance (CTSIB) (Shumway-Cook & Horak, 1986), functional
reach (FR), repetitive reach (RR), step test (ST), gait velocity, stride length
and the Motor Assessment Scale (Carr et al., 1985) (walking item) were assessed
at each interval. RESULTS: All measures of dynamic balance showed significant
change over the four-week measurement period (p < 0.0036). Factor analysis
identified two factors which grouped tests into static and dynamic, with a trend
towards a third factor incorporating bipedal dynamic tests. Tests of static
balance suffered from ceiling effects, whereas dynamic tests of balance and gait
suffered from floor effects. Dynamic tests were more responsive (Standardized
Response Measure (SRM) > 0.75) to change over the rehabilitation period than
static tests. CONCLUSIONS: The findings suggest that a clinically useful and
responsive balance and mobility test battery should include one component of the
CTSIB (Shumway-Cook & Horak, 1986), RR (step stance), ST and gait velocity.
PMID- 9648177
TI - Curricular content on urinary incontinence in entry-level physical therapy
programmes in three countries.
AB - BACKGROUND AND PURPOSE: Urinary incontinence (UI) is a significant psychological,
social and healthcare problem across the lifespan. Although there is evidence of
physical therapy (PT) efficacy, no literature was located pertaining to UI in PT
curricula. The aim was to compare curricular content on UI (of non-neuropathic
origin) in PT programmes in Canada, the UK and the USA. The study subjects were
PT educators in entry-level programmes. METHODS: All Canadian PT programmes (13)
were surveyed. Stratification was used to make random samples of PT programmes:
50% of UK (13/26) and 50% of USA (69/136). A questionnaire was used to obtain
information on: degree level, programme length, specific courses, time allotted,
UI topics, teaching method(s), the professional teaching patients with UI and
reasons for non-inclusion in the study. One follow-up letter was sent. Results
are presented as frequencies and percentages. RESULTS: Overall, the response rate
was 62.8%; country response rates were: Canada 92.3%; UK 76.9% and USA 53.6%. UI
was taught in 80% of Canadian, 90% of UK (which gave the most time to teaching on
UI: 70% > 60 minutes) and 78.4% of USA PT programmes. Kegel exercises were taught
in all three countries (> 81.1%) and electrical stimulation in > 65%. Theory only
was the primary method of teaching in all countries (> 64.9%). Physical
therapists were reported to have a major role in treating patients with UI
(Canada > 75%; UK 100%; USA 70.3%). CONCLUSIONS: With Kegel exercises and
electrical stimulation taught in two-thirds of all programmes physical therapy
graduates may have some knowledge of UI management. However, for the UK and USA
programmes data are from only 38.5% and 27% respectively. As the common method of
teaching on UI was by theory only, graduating physical therapists may lack the
clinical skills to apply assessment and treatment techniques.
PMID- 9648178
TI - Inter- and intra-tester reliability of the Balance Performance Monitor in a non
patient population.
AB - BACKGROUND AND PURPOSE: There is a growing interest in the measurement and
evaluation of balance deficits and a number of instruments for measurement are
now available. However, few data exist that accurately describe the reliability
when using these measurement tools. This study was designed to evaluate the inter
and intra-tester reliability of using the Balance Performance Monitor (BPM) (SMS
Healthcare) in a non-patient population. METHODS: A total of 58 subjects (mean
age 29.83 years (+/- 9.44 years)) and three testers participated in two separate
experiments. Intra Class Correlation Coefficients (ICCs) and coefficients of
variation were used to describe the reliability of two different protocols for
positioning subjects on the footplates of the BPM. RESULTS: Measurements of
weight distribution showed high and significant inter- and intra-tester
reliability for both protocols (ICCs ranging from 0.720 to 0.868). Sway
measurements showed more limited reliability (ICCs ranging from 0.183 to 0.775).
Coefficients of variation were low for weight distribution measurements and high
for sway measurements. CONCLUSIONS: Taking the mean of three measurements is
recommended for both the weight distribution and the sway measurements as it has
shown to produce acceptable measurement results.
PMID- 9648179
TI - An unlikely case for successful rehabilitation?
PMID- 9648180
TI - Associated reactions: their value in clinical practice?
PMID- 9648181
TI - Normal mechanisms of heat and moisture exchange in the respiratory tract.
AB - The initial conditioning of the inhaled gases occurs in the upper respiratory
tract. The conditioned gases are at approximately 32 degrees C and more than 95%
relative humidity as they enter the lower respiratory tract. This level of heat
and humidity will preserve the body's defense mechanisms. When the upper airway
is bypassed the gases being delivered to the lower airways need to be as close to
physiologic levels as possible based on the length of time the endotracheal tube
will be in place. The delivery of gases above or below normal physiologic levels
has been shown to produce clinical problems.
PMID- 9648182
TI - The effects of inadequate humidity.
AB - The use of heated humidification in adults does not appear to be an important
factor in maintaining body temperature in adults. Heat and moisture losses
certainly can be reduced with heated humidification, but the contribution to
temperature regulation appears small. The use of an HME reduces heat loss form
the respiratory tract, but this loss is minute compared with losses from the
skin, fluid administration, and the operative site. In neonates, the use of
heated humidification during surgery may help contribute to thermal balance owing
to the unique issues of temperature regulation and control in these patients.
PMID- 9648183
TI - The effects of excessive humidity.
AB - Humidification devices and techniques can expose the airway mucosa to a wide
range of gas temperatures and humidities, some of which are excessive and may
cause injury. Humidified gas is a carrier of both water and energy. The volume of
water in the gas stream depends on whether the water is in a molecular form
(vapor), particulate form (aerosol), or bulk form (liquid). The energy content of
gas stream is the sum of the sensible heat (temperature) of the air and any water
droplets in it and the heat of vaporization (latent energy) of any water vapor
present. Latent heat energy is much larger than sensible heat energy, so
saturated air contains much more energy than dry air. Thus every breath contains
a water volume and energy (thermal) challenge to the airway mucosa. When the
challenge exceeds the homeostatic mechanisms airway dysfunction begins, starting
at the cellular and secretion level and progressing to whole airway function. A
large challenge will result in quick progression of dysfunction. Early
dysfunction is generally reversible, however, so large challenges with short
exposure times may not cause irreversible injury. The mechanisms of airway injury
owing to excess water are not well studied. The observation of its effects lends
itself to some general conclusions, however. Alterations in the ventilation
perfusion ratio, decrease in vital capacity and compilance, and atelectasis are
suggestive of partial or full occlusion of small airways. Changes in surface
tension and alveolar-arterial oxygen gradient are consistent with flooding of
alveoli. There also may be osmotic challenges to mucosal cell function as
evidenced by the different reaction rates with hyper- and hypotonic saline. The
reaction to nonisotonic saline also may partly explain increases in specific
airway resistance. Aerosolized water and instilled water may be hazardous because
of their demonstrated potential for delivering excessive water to the airway.
Their use for airway humidification or toilet should be eliminated or minimized.
Water vapor is the best form of humidification because it is unlikely to deliver
sufficient water to cause pulmonary injury. The mechanisms of thermal injury in
epidermal cells have been well studied, although specific observations of injury
mechanisms in the airway are sparse. The findings of the epidermal studies can
readily be applied to airway mucosal cells, however. This work demonstrates that
it is prudent to avoid raising the average tracheal mucosal temperature above
approximately 43 degrees C to 45 degrees C. Thus respiratory gases that arrive at
the tracheal end of the endotracheal tube should average less than 43 degrees C
to 45 degrees C and 100% RH. It should be noted that to deliver temperatures of
this magnitude in the trachea would require higher gas temperatures at the
circuit wye. These temperatures are much greater than the upper temperature
limits imposed on humidifiers by international standards. Additionally, the
reports to date of pulmonary thermal injury associated with humidifiers have been
solely as the result of equipment malfunction or misuse--a situation that is
increasingly less likely to occur with the control and monitoring features of
modern devices. In summary, to avoid the injurious effects of excess heat and
water in the airway, inspiratory gases should be delivered to the patient's
airway at core temperature and 100% RH. This gas condition is the only one that
is neutral to the airway mucosa and poses no water volume and heat energy
challenge. Humidifiers, however, do not measure the gas temperature at the
patient airway but only at the circuit wye. To compensate for any cooling of the
gas as it passes from the wye to the patient the gas temperature at the wye must
be set higher than core temperature. To safely avoid the risk that this higher
temperature may accidentally reach the patient and cause an injury, the average
gas temperature at the wye should restricted to less than 43 degrees
PMID- 9648184
TI - Measuring temperature and humidity in the breathing circuit.
AB - Accurate measurement of temperature and humidity in the breathing circuit can be
a difficult task. This article introduces basic humidity concepts, outlines the
problems that are unique to the breathing circuit, and describes the various
methods that are available to measure temperature and humidity. Recommendations
are made on how to measure temperature and humidity in four commonly encountered
situations.
PMID- 9648185
TI - Heated humidifiers. Structure and function.
AB - Humidity in the form of molecular water vapor is an essential requirement for
intubated patients, and can be beneficial to nonintubated patients receiving CPAP
or oxygen therapy. There are many different types of humidification devices but
they generally consist of a humidity generator (or water reservoir) and humidity
delivery system (or breathing circuit). Humidifiers that generate aerosols may
provide adequate humidity, but they also provide a transport mechanism for
contaminants and may deliver excess water to the airways. An ideal system
generates the required amount of humidity, in the form of water vapor, at the
correct temperature, and transports it to the patient without the loss of either
heat or moisture. The most effective way to achieve this is to use a large heated
water surface for the generator, and heating elements within the delivery system
to prevent condensation. This system can be configured to provide optimal
humidity for both intubated and nonintubated patients from the neonatal to the
adult intensive care unit. Heated humidifiers have no contraindications and can
be used on any patient requiring ventilatory assistance or supplemental oxygen.
PMID- 9648186
TI - Heat and moisture exchangers. Structure and function.
AB - A bewildering array of HMEs are available, suited to many different tidal volume
and other clinical requirements. Choosing among the different devices depends on
many attributes. Grouping different HMEs together to describe their performance
may be inappropriate. Independent tests on HMEs provide information to help when
choosing among different devices, but care should be exercised to prevent
inappropriate comparisons being made between results from studies using different
test procedures and protocols. The use of filters in anesthesia is recommended in
some countries. Some HMEs have a high moisture-conserving performance, but the
use of HMEs may be inappropriate for some patient groups, and other humidifying
devices may be more suitable.
PMID- 9648187
TI - Humidification during anesthesia.
AB - Humidification during anesthesia is important to prevent adverse changes in the
upper airways and possible pulmonary compromise. These changes may take place in
less than 1 hour using dry nonhumidified anesthetic gases. Consequently, some
method of humidification should be employed for all but the shortest of surgical
procedures requiring general anesthesia. Methods of humidification include the
anesthesia breathing system itself, passive humidification or conservation of
moisture (the use of HMEs), and active humidification. The simplest system
providing good levels of humidification and warming of anesthetic gases is the
Circle system, which uses a fresh gas flow of less than 2 L/min. Its success can
be further enhanced by use of a coaxial circuit. The minimum levels of water
output or humidity required in the breathing circuit remain controversial. It may
be preferable to have a gas with a lower temperature and higher relative humidity
because a warmer gas that is less saturated may result in increased desiccation
from the upper airways. Humidification for neonatal and pediatric patients
requires special consideration of resistance, work of breathing, and dead space.
Further work is necessary with regard to the use of HMEs in this population of
patients undergoing general anesthesia.
PMID- 9648188
TI - Humidification practices in the Adult Intensive Care Unit, Prince of Wales
Hospital.
AB - In the Adult Intensive Care Unit of The Prince of Wales Hospital, Sydney,
Australia, inspiratory gas is humidified to saturation at 37 degrees C. This
stops the buildup of dried sputum within the endotracheal tubes and thus prevents
blocked tubes and the increased resistance caused by partial obstruction.
Inspiratory and expiratory hose heater wires are used to produce a completely dry
circuit, allowing the elimination of water traps and circuit support arms without
the resistance of a heat and moisture exchanger.
PMID- 9648189
TI - Humidification in the intensive care unit.
AB - In summary, current data indicate that body temperature cannot be controlled
efficiently by changing inspired gas temperature. Inspired gas temperature should
therefore be maintained at 32 degrees C to 34 degrees C for intubated patients
and other efforts should be made to optimize body temperature.
PMID- 9648190
TI - What is optimum humidity?
AB - The relevant aspects of the normal physiology of the airway mucosa and the
customary ways of describing humidity are briefly reviewed. The need for
surrogate markers of optimum humidity is identified, and two such markers are
proposed. The relationship between the humidity of the inspired gas and mucosal
function is examined using a model that is then validated. Optimum humidity is
achieved when the inspired gas is at body core temperature and 100% relative
humidity.
PMID- 9648191
TI - The role of filtration during humidification.
AB - Nosocomial pneumonia remains an important problem in patients undergoing
mechanical ventilation, being associated with high mortality and morbidity and
considerable expenditure. In the past respiratory equipment has been implicated
in the development of nosocomial pneumonia and strict recommendations for
cleaning and maintenance have been practiced. It is now known that the circuit
and other equipment rapidly become contaminated with microorganisms originating
from the patient's upper airway flora. These organisms access the circuit through
suctioning and coughing, and may contaminate distant sites by traveling in
association with aerosols or condensate. Current evidence suggests that circuit
contamination usually is a result rather than a cause of airway colonization and
does not have an important role in the pathogenesis of nosocomial pneumonia.
Provided that reasonable infection control measures are taken, circuit
contamination does not pose a risk to the ventilated patient. Although bacterial
filters placed in the circuit effectively prevent circuit contamination they do
not significantly reduce the incidence of nosocomial pneumonia in patients
receiving mechanical ventilation.
PMID- 9648192
TI - Treatment of fracture and complication of cervical spine with ankylosing
spondylitis.
PMID- 9648193
TI - Locomotor pattern in paraplegic patients: training effects and recovery of spinal
cord function.
AB - Recent studies have shown that a locomotor pattern can be induced and utilized by
paraplegic patients under conditions of body unloading using a moving treadmill.
The present study investigated the behaviour of the locomotor pattern and also
the relationship of its development to the spontaneous recovery of spinal cord
function assessed by clinical and electrophysiological (tibial nerve
somatosensory evoked potentials and motor evoked potentials) examinations. The
earliest time that spinal locomotor activity could be induced was when signs of
spinal shock had disappeared. This activity was distinct from spinal stretch
reflex activity. In complete paraplegic patients the locomotor pattern improved
spontaneously without training. This was coincident with both an increase of
gastrocnemius electromyographic activity during the stance phase of gait and a
decrease of body unloading. These effects reached a plateau after about 5 weeks.
In complete and incomplete paraplegic patients a near linear increase of
gastrocnemius electromyographic activity occurred during the stance phase of a
step cycle with daily locomotor training over the whole training period of 12
weeks. This was also coincident with a significant decrease of body unloading. In
contrast to this, neither clinical nor electrophysiological examination scores
improved after the onset of training in both patient groups. Only in incomplete
paraplegic patients was there recovery, albeit statistically insignificant, of
spinal cord function according to the sensory and motor scores obtained in the
neurological examination during the time period before onset of training. An
improvement of locomotor function by training was also seen in patients with
paraplegia due to a cauda lesion. Such training effects on muscles and tendons
could be separated from those on the spinal locomotor centres. The findings of
this study may be relevant for the future clinical treatment of paraplegic
patients.
PMID- 9648194
TI - Lateral approach of the dog brachial plexus for ventral root reimplantation.
AB - A lateral surgical approach of the cervical spinal cord and brachial plexus was
developed in nine dogs for avulsion and reimplantation of the ventral cervical
spinal roots (C). The surgical steps involved in exposing the spinal cord and
roots are described. The avulsed rootlets of C6 and C7 were reimplanted in their
initial position. As a direct consequence of the avulsion, flaccid paralysis of
the shoulder and severe amyotrophy developed within 5-7 weeks on the injured
side. In addition, the dogs exhibited clinical signs resulting from damage to
long fiber tracts due to the reimplantation procedure. A partial recovery of
these deficits was observed during the 6 postoperative months. Retrograde axonal
tracing with horseradish peroxidase applied to the distal stump of the
musculocutaneous, suprascapular, and subscapular nerves (originating from C5, C6
and C7) revealed the presence of labelled neuronal somata that were located in
the ipsilateral ventral horn, close to the tip of the reimplanted rootlets. It is
concluded that the dog constitutes a worthwhile animal model for the study of
avulsion and reimplantation of brachial plexus root via a lateral surgical
approach.
PMID- 9648195
TI - Cervical myeloradiculopathy with entrapment neuropathy: a study based on the
double-crush concept.
AB - In an attempt to formulate a standardised approach to the diagnosis and
management of patients with the double-crush syndrome, we reviewed 65 surgical
cases (39 men and 26 women) with cervical myeloradiculopathy associated with
entrapment neuropathy in the arm by examining the clinical features, results of
nerve conduction velocity studies and distribution of the vertebral levels of
compression. Fifty-three patients (average age, 43 years) presented with a carpal
tunnel syndrome at the wrist and cervical lesions (41 with spondylosis and 12
with ossified posterior longitudinal ligament), while 12 had a cubital tunnel
syndrome at the elbow with cervical lesions (eight with spondylosis and four with
ossification of the posterior longitudinal ligament). In the former group, the
lesions were found mostly at C5-6 and C6-7 levels, while in the latter group
involvement of C6-7 was frequently observed. Two patients in each group required
additional cervical decompression after carpal or cubital tunnel release. A
retrospective review of our patients suggested that it is reasonable to pursue an
accurate diagnosis followed by treatment based on individual neurological and
electrophysiological findings, but taking into consideration the significant
level of physical impairment associated with cord compromise, we believe that it
may be reasonable to perform a cervical decompression rather than peripheral
nerve release in such cases. Our findings suggest that one should be aware of a
double-crush during examination of patients complaining of neck and hand
problems.
PMID- 9648196
TI - Factors associated with contractures in acute spinal cord injury.
AB - The purpose of this study was to examine the occurrence of contractures in acute
SCI and clarify possible contributing factors such as early versus late
admission, level of injury, completeness of the lesion, pressure ulcers,
spasticity, co-existent head injury, extremity fractures, heterotopic
ossification (HO), peripheral nerve injury, and shoulder pain. The records of all
patients (n = 482) admitted between 1990 and 1995 with acute SCI to a model SCI
system were reviewed. Of 482 patients 44 (9%) (33 male, 11 female) developed
contractures during their initial hospitalization. There were 30 tetraplegic and
14 paraplegic patients. Thirty-four patients had complete and 10 patients had
incomplete lesions. The percentage of occurrence of contractures among patients
admitted to the model system on the day of injury was 7.6% and among those
admitted between 2 and 60 days of the injury was 15% (P = 0.05). Patients with a
pressure ulcer (14.1%) were significantly more likely to have a contracture than
patients without a pressure ulcer (7.1%) (P = 0.05). Contractures were also more
common in patients with spasticity requiring medication; 12.7% of patients with
spasticity compared to 7.8% without spasticity, had contractures (P < 0.05).
Patients with a co-existent or suspected head injury (15%) were more likely to
have contractures than patients without it (7.4%)(P < 0.05). Eighteen patients
with a contracture had HO, extremity fracture, peripheral nerve injury or reflex
sympathetic dystrophy. In conclusion, this study is one of the first to
demonstrate a significant association of contractures in acute SCI with pressure
ulcers and co-existent head injury and reaffirms the importance of early
admission to a coordinated SCI center in the prevention of contractures.
PMID- 9648197
TI - Effect of intermittent urethral catheterization and oxybutynin bladder
instillation on urinary continence status and quality of life in a selected group
of spinal cord injury patients with neuropathic bladder dysfunction.
AB - OBJECTIVES: A comparative assessment of (i) urinary continence status, (ii)
quality of life, and (iii) sexuality in spinal cord injury patients prior to, and
during intermittent catheterization with adjunctive intravesical oxybutynin
therapy (Cystin: manufactured by Leiras Oy. Helsinki, Finland). SETTING: A
hospital, and community-based study of selected adult, male, spinal cord injury
patients registered with the Regional Spinal Injuries Centre, Southport.
PATIENTS: Seven patients (mean age: 44.3 years) suffering from neuropathic
bladder due to suprasacral spinal cord lesion of traumatic aetiology, and well
settled in the community in the north-west of England were the subjects of this
study. Before commencing the intermittent catheterization regime, these patients
were on penile sheath drainage. INTERVENTION: Intermittent urethral
catheterization was performed with sterile, single-use Nelaton catheters 5-6
times a day with intravesical instillation of oxybutynin 5 mg in 30 ml. 1-3 times
a day for periods ranging from 14 to 30 months. OUTCOME MEASURES: Assessment of
urinary continence, sexuality, and quality of life was made (i) at the outset
before any intervention, (ii) during intermittent catheterization regime, and
(iii) when the patients were using the oxybutynin bladder instillation along with
intermittent catheterization. RESULTS: Initially all the seven patients were
constantly wearing penile sheaths and leg bags. When these patients performed
intermittent catheterization 5-6 times in 24 h, they attempted to discard the
penile sheath during the day but they were experiencing mild to moderate urine
leak between catheterization. They were compelled to wear penile sheaths during
night. Subsequently, five patients took oxybutynin by mouth, but developed an
unacceptable degree of side-effects necessitating discontinuation of the
medication. Following commencement of intravesical oxybutynin therapy, all of
them were able to discard the penile sheaths and leg bags during the day as well
as during the night. However, on waking-up after a full night's sleep, three
patients found dampness of their undergarments 1-2 times per week. None of the
patients experienced side-effects attributable either to the intermittent
catheterization procedure, or to the intravesical oxybutynin therapy. The number
of episodes of urinary infection requiring antibiotic therapy was
0.08/patient/month. All the seven patients noticed a remarkable improvement in
the quality of life because they had achieved a high degree of continence. All
the seven patients commented on the improved sense of their own sexuality which
was attributed to (i) absence of incontinence episodes, (ii) improved self-image,
and (iii) not wearing penile sheaths and leg bags. CONCLUSION: These seven spinal
cord injury patients achieved socially acceptable continence with improved
quality of life, and enhanced sexuality with the intermittent urethral
catheterization regime and intravesical oxybutynin therapy.
PMID- 9648198
TI - Camel collision as a major cause of low cervical spinal cord injury.
AB - One hundred and forty patients with low cervical spinal cord injuries, who were
admitted to the Riyadh Armed Forces Hospital over the past 10 years were
reviewed. Motor vehicle accidents constituted 119 (85%) of the patients. Camel
collisions were a major cause of vehicle accidents 39 (33%), after rollover
accidents 70 (59%), and much more than head on collisions 9 (7.5%). Male to
female ratio was 14:1 with a mean age of 32 years. Camel collision although a
commonly observed cause of motor vehicle accidents in the Middle East has not
been mentioned in the literature before. The mechanism of injury is not much
different, but the exact description of the accident and sustaining injury is
interesting because it leads to localised damage to the neck without major body
trauma and mortality.
PMID- 9648199
TI - Shoulder and elbow motion during two speeds of wheelchair propulsion: a
description using a local coordinate system.
AB - Individuals who propel wheelchairs have a high prevalence of upper extremity
injuries. To better understand the mechanism behind these injuries this study
investigates the motion of the shoulder and elbow during wheelchair propulsion.
The objectives of this study are: (1) To describe the motion occurring at the
shoulder and elbow in anatomical terms during wheelchair propulsion; (2) to
obtain variables that characterize shoulder and elbow motion and are
statistically stable; (3) to determine how these variables change with speed. The
participants in the study were a convenience sample of Paralympic athletes who
use manual wheelchairs for mobility and have unimpaired arm function. Each
subject propelled an ultralight wheelchair on a dynamometer at 1.3 and 2.2 meters
per second (m/s). Biomechanical data was obtained using a force and moment
sensing pushrim and a motion analysis system. The main outcome measures
investigated were: maximum and minimum angles while in contact with the pushrim,
range of motion during the entire stroke and peak accelerations. All of the
measures were found to be stable at both speeds (Cronbach's alpha > 0.8). The
following measures were found to differ with speed (data format: measure at 1.3
m/s +/- SD; measure at 2.2 m/s +/- SD): minimum shoulder abduction angle during
propulsion (24.5 degrees +/- 6.7, 21.6 degrees +/- 7.2), range of motion during
the entire stroke in elbow flexion/extension (54.0 degrees +/- 9.9, 58.1 degrees
+/- 10.4) and shoulder sagittal flexion/extension (74.8 degrees +/- 9.4, 82.6
degrees +/- 8.5), and peak acceleration in shoulder sagittal flexion/extension
(4044 degrees/s2 +/- 946, 7146 degrees/s2 +/- 1705), abduction/adduction (2678
degrees/s2 +/- 767, 4928 degrees/s2 +/- 1311), and elbow flexion/extension (9355
degrees/s2 +/- 4120, 12889 degrees/s2 +/- 5572). This study described the motion
occurring at the shoulder and elbow using a local coordinate system. Stable
parameters that characterize the propulsive stroke and differed with speed were
found. In the future these same parameters may provide insight into the cause and
prevention of shoulder and elbow injuries in manual wheelchair.
PMID- 9648200
TI - Reliability of a tool for assessing mobility in wheelchair-dependent paraplegics.
AB - The aim of this study was to design and test the reliability of an assessment
tool that could be used by physiotherapists to quantify the mobility of
wheelchair-dependent paraplegics. The assessment tool examined six key tasks
fundamental to the mobility of wheelchair-dependent paraplegics, comprising
moving from lying to sitting, completing a horizontal transfer, completing a
vertical transfer, pushing on flat ground, pushing on ramps and negotiating
kerbs. A six-point scoring system was used to assess the level of mobility
attained by subjects on each task. The scoring system was different for each task
and took into account the level of assistance and time required to complete the
task or the complexity of the task. Twenty wheelchair-dependent paraplegics were
assessed independently by two therapists using the assessment tool. The Cohen's
Weighted Kappas describing inter-rater reliability of each task ranged between
0.82-0.96, indicating a high reliability between therapists. It was concluded
that the assessment tool is a reliable way of assessing the mobility of
wheelchair-dependent paraplegics.
PMID- 9648201
TI - Post traumatic paraplegics living in Athens: the impact of pressure sores and
UTIs on everyday life activities.
AB - This paper contains the findings of a scientific research which was done on post
traumatic paraplegics who live in the area of Athens. Greece, and measured the
impact of pressure sores and UTIs on their everyday life activities. The target
population was 127 individuals out of which 98 were observed and interviewed. A
semi-structured questionnaire which consisted of two parts used; the first part
of the questionnaire included general questions whereas the second contained the
Sarno Functional Life Scale (SFLS) which is a tool measuring the level of
independence of disabled people. Sixty-two per cent of the population was male.
The mean age of the sample population at the time they had the accident which
caused the paraplegia was 31.5, while the median was 28.5. The majority of the
subjects comes from the lower socioeconomic class. Traffic accidents accounted
for the 55% of the occurrences of paraplegia, falls for 37%, surgical
complication for 4% and athletic activities for the remaining 4%. Forty-nine
percent of the sample had been hospitalised in a rehabilitation centre. However,
the multiple regressions used did not reveal any statistically significant
relation between the hospitalisation in a rehabilitation centre and the
paraplegic's scores in any of the Sarno Functional Life Scale's (SFLS) variables.
Instead, the multiple regressions employed yielded paraplegics' scores in the
SFLS's everyday life activities that were negatively related to age (P = 0.004)
and pressure sores (P = 0.021). The paraplegics' scores on the SFLS's indoors
activities are positively related to the years since injury (P = 0.048) and
health education on daily fluid consumption (P = 0.003). The scores of the
subjects on the SFLS's outdoor activities are positively related to the years of
education (P = 0.008), the years since injury (P = 0.011), while are negatively
related to pressure sores (P = 0.034) and UTIs (0.044). The subjects' scores on
the SFLS variables regarding social relations had a negative relation to sex,
(female) (P = 0.0001), age (P = 0.001) and pressure sores (P = 0.019), while they
have a positive relation with the years since injury (P = 0.024).
PMID- 9648202
TI - Spinal cord injury management in Salisbury: the history of the Duke of Cornwall
Spinal Treatment Centre.
AB - One point remains paramount in our minds and that is, in order to achieve the
goals we have set, we need vigorously to ensure that Spinal Units continue to be
seen as the only facilities competent to provide for the diverse needs of spinal
cord injured patients. We at the Duke of Cornwall Spinal Treatment Centre are
fortunate in having a first class, expanding facility and have the tireless
cooperation of both our staff and those of the other departments in Salisbury. We
recognize also that we can play a leading role in the treatment of patients, not
only from the Southwest, but, where and when appropriate, from further afield.
PMID- 9648203
TI - Neuromuscular electrical stimulation keeps a tetraplegic subject in his chair: a
case study.
AB - Pressure ulcers are an important complication of spinal cord injury which place
an enormous burden on society due to their financial, psychosocial, and
vocational implications. Although they are now rarely fatal, they can still have
devastating consequences, often needing prolonged hospitalisation to be properly
managed. This study reviews the use of electrical stimulation to overcome
increasing debility due to sacral pressure ulcers and saddle soreness in a man
with tetraplegia. After 24 months of regular cyclic stimulation he had increased
circumferential dimensions across his buttocks by up to 21%, and increased his
sitting tolerance.
PMID- 9648204
TI - A review of the respiratory management of a patient with high level tetraplegia.
PMID- 9648205
TI - Heat capacities of amino acids, peptides and proteins.
AB - The heat capacity is one of the fundamental parameters describing thermodynamic
properties of a system. It has wide applications in a number of areas such as
polymer chemistry, protein folding and DNA stability. To aid the scientific
community in the analysis of such data, I have compiled a database on the
experimentally measured heat capacities of amino acids, polyamino acids,
peptides, and proteins in solid state and in aqueous solutions.
PMID- 9648206
TI - Effects of metal binding affinity on the chemical and thermal stability of site
directed mutants of rat oncomodulin.
AB - Tryptophan fluorescence was used to study the stability and unfolding behavior of
several single tryptophan mutants of the metal-binding protein rat oncomodulin
(OM); F102W, Y57W, Y65W and the engineered protein CDOM33 which had the 12
residues of the CD loop replaced with a more potent metal binding site. Both the
thermal and the chemical stability were improved upon binding of metal ions with
the order apo < Ca2+ < Tb3+. During thermal denaturation, the transition
midpoints (T(un)) of Y65W was the lowest, followed by Y57W and F102W. The
placement of the Trp residue in the F-helix in F102W made the protein slightly
more thermostable, although the fluorescence response was readily affected by
chemical denaturants, which acted through the disruption of hydrogen bonds at the
C-terminal end of the F-helix. Under both thermal and chemical denaturation, the
engineered protein showed the highest stability. This indicated that increasing
the number of metal ligating oxygens in the binding site, either by using a metal
ion with a higher coordinate number (i.e., Tb3+) which binds more carboxylate
ligands, or by providing more ligating groups, as in the CDOM33 replacement,
produces notable improvements in protein stability.
PMID- 9648207
TI - Contributions of solvent-solvent hydrogen bonding and van der Waals interactions
to the attraction between methane molecules in water.
AB - The contribution of solvent-solvent hydrogen bonding and van der Waals
interactions to the attraction between methane molecules in water was
investigated by comparing the potential of mean force (PMF) between two methane
molecules in TIP4P water to those in a series of related liquids in which the
solvent-solvent interactions were progressively turned off while keeping the
solvent-solute interactions unchanged. The magnitude of the attraction between
methanes was not significantly changed when the hydrogen bonding interaction
between solvent molecules was eliminated and the solvent was maintained in the
liquid state by increasing either the pressure or the magnitude of the solvent
solvent van der Waals interaction. However, when solvent-solvent excluded volume
interactions were eliminated, the methane molecules interacted no more strongly
than in the gas phase. The results are consistent with the idea that the primary
contribution of hydrogen bonding to the hydrophobic interaction is to keep water
molecules in a liquid state; at constant density, packing interactions rather
than hydrogen bonding appear to be critical as suggested by scaled particle
theories of solvation. The overall shape of the PMF was, however, changed in the
absence of hydrogen bonding, pointing to an influence of hydrogen bonding on the
detailed form of the interactions between nonpolar solutes in water. The effects
of correlations between the configurations sampled during the Monte Carlo
procedure used in the free energy calculations on the estimation of errors was
also characterized.
PMID- 9648208
TI - Near UV circular dichroism from biomimetic model compounds define the
coordination geometry of vanadate centers in MeVi- and MeADPVi-rabbit myosin
subfragment 1 complexes in solution.
AB - The circular dichroism (CD) spectrum was measured from vanadate (Vi) cyclic
esters of chiral vicinal diols, hydroxycarboxylates, and cyclodextrines as a
function of Vi concentration ([Vi]) and at the lowest energy transitions of the
vanadium. At low [Vi] and in the presence of excess vicinal diols,
hydroxycarboxylates, or cyclodextrines the CD signal intensity scales linearly
with [Vi] indicating the predominance of a monomeric cyclic ester. At higher
[Vi], the signal intensity in the presence of the vicinal diols and
hydroxycarboxylates become nonlinear in [Vi], indicating formation of a dimeric
cyclic ester. Vanadium-51 NMR (51V-NMR) indicates the coordination geometry of
several of these model Vi centers in solution and identifies the CD signals
characteristic to Vi trigonal bipyramidal (tbp) and octahedral (Oh) coordination
geometries from monomeric and dimeric species. The CD spectra from monomeric and
dimeric forms of the tbp-coordinated model compounds have two apparent
transitions with amplitudes of opposite sign at wavelengths > or = 240 nm.
Spectra from the monomeric and dimeric Oh coordinated species are distinct from
the tbp-type spectra over the same wavelength domain because of the presence of
two additional transitions with opposite sign amplitudes. These model spectra
were compared to the vanadate CD spectra from Vi bound to rabbit myosin
subfragment 1 (S1) in solution, in the presence of divalent metal cations (MeVi
S1) or trapped with MeADP (MeADPVi-S1). Polymeric MeVi binds to the active site
of S1 and the vanadate centers in MnVi-S1 or CoVi-S1 produce a CD signal
resembling that from the tbp model. The trapped ATPase transition state analog
MeADPVi produces a different CD signal resembling that from the Oh model.
PMID- 9648209
TI - Characterization of the interaction between bovine pancreatic trypsin inhibitor
and thiocyanate by NMR.
AB - The interaction between Bovine Pancreatic Trypsin Inhibitor and thiocyanate was
studied using NMR spectroscopy following several experimental approaches. The
chemical shift variations of the BPTI protons in the absence and in the presence
of increasing thiocyanate concentrations (up to 0.2 M) were significant (> 0.05
ppm) for 30 protein protons belonging to 20 residues. The largest deviation, 0.2
ppm, was observed for the amide backbone proton of Arg42 in the absence of
thiocyanate and in the presence of 40 molar equivalents of thiocyanate. The
influence of the presence of thiocyanate on the electrostatic potential
surrounding the protein was demonstrated by NOESY spectra selective at the water
frequency: the presence of SCN- favours acid catalysed exchange and disfavours
base catalysis. However, a specific effect of thiocyanate was pointed out since
the comparison of the chemical shifts in the presence of 40 molar equivalents of
KSCN and KCl, respectively, showed much more as well as larger deviations
compared to measurements in the absence of salt. A dissociation constant, KD, for
a 1/1 complex between BPTI and thiocyanate was calculated from chemical shifts
measurements: KD = 89 +/- 8 mM. A second value, KD = 99 +/- 10 mM, was extracted
from SC15N relaxation time measurements.
PMID- 9648210
TI - Transient kinetics and thermodynamics of anthroylouabain binding to Na/K-ATPase.
AB - The Na/K-ATPase is an integral membrane protein enzyme which uses energy derived
from hydrolysis of ATP to pump Na+ out of and K+ into the cell. Ouabain belongs
to a class of drugs known as cardiac glycosides, which are useful for treating
congestive heart failure. Therapeutic value is achieved when these drugs bind to
and inhibit the Na/K-ATPase of cardiac muscle. We gain insight into this
important interaction by measuring the thermodynamics of the interaction of
anthroylouabain (AO), a fluorescent derivative of ouabain, with the Na/K-ATPase.
AO has the useful property that its fluorescence intensity is greatly enhanced
(approximately 10x) when it binds to the enzyme. Using this enhancement, we
measure temperature dependence of transient kinetics for the association and
dissociation of AO interacting with membrane fragments of Na/K-ATPase purified
from dog kidney. Using a standard Eyring analysis, we find that the overall
association of AO with the enzyme is driven by substantial contributions from
both enthalpy and entropy, and that in an energy diagram for the association
pathway, the free energy change is quite similar to that of ouabain deduced from
previously published results [E. Erdmann, W. Schoner, BBA 307 (1973) 386].
However, in the transition state, there are substantial differences for the
enthalpy and entropy, presumably due to the presence of the anthracene moiety.
PMID- 9648211
TI - Increased cellulose production from sucrose with reduced levan accumulation by an
Acetobacter strain harboring a recombinant plasmid.
AB - Cellulose production from sucrose by Acetobacter strains is accompanied by the
accumulation of a water-soluble polysaccharide, called levan. To improve
cellulose productivity, a levansucrase-deficient mutant, LD-2, was derived from
Acetobacter strain 757 and used as a host for the construction of recombinant
strains. An LD-2 mutant harboring a plasmid containing the sucrase gene, sucZE3,
from Zymomonas mobilis together with zliS, a gene that encodes a secretion
activating factor under the control of the Escherichia coli lac promoter, had
sucrase activity and produced much cellulose and little levan in a medium
containing sucrose. In addition, a mutant levansucrase gene, mutant sacB, from
Bacillus subtilis, which encodes a protein with little levan-forming activity,
was generated by site-directed mutagenesis and introduced into the LD-2 mutant.
This introduction also resulted in the higher cellulose productivity and little
levan.
PMID- 9648212
TI - Effects of difructose anhydride III on calcium absorption in small and large
intestines of rats.
AB - Difructose anhydride III (DFA III; di-D-fructo-furanose 1,2':2,3' dianhydride)
was prepared from inulin with Arthrobacter sp. H65-7 inulin fructotransferase
(depolymerizing (inulase II; EC 2.4.1.93). DFA III is not hydrolyzed by enzymes
in the small intestine, but is metabolized by microorganisms in the large
intestine. We investigated the effects of DFA III on calcium absorption in two
experiments. In the in vivo experiment, we examined the effects of DFA III,
fructooligosaccharides, and raffinose on calcium absorption in male Sprague
Dawley rats 5 weeks old at start of the experiment and given feed containing 3%
of one of these oligosaccharides for two weeks. The apparent calcium absorption
was significantly higher in rats fed any of these oligosaccharides than in
control rats, and the increase with DFA III was the greatest. Absorption in both
the small and large intestines was affected. In rats fed DFA III, the cecal wall
thickened and soluble calcium and the amounts of some organic acids were higher
than in the control groups. In an in vitro experiment with everted jejunal and
ileal sacs of rats, calcium absorption was higher when DFA III was present in the
mucosal fluid at all concentrations tested (up to 200 mM). In the jejunal sacs,
the increase in calcium absorption depended on the DFA III concentration. In the
ileal sacs, the absorption was maximum at 50 mM DFA III and did not increase
further at higher concentrations. These results indicate that intact DFA III
stimulates calcium absorption in the small intestine, and that cecal fermentation
of DFA III may contribute to the increase in calcium absorption by the large
intestine.
PMID- 9648213
TI - Physiological role of L-ascorbic acid in rats exposed x887p6arette smoke.
AB - This study clarifies the effect of exposure to cigarette smoke on L-ascorbic acid
(AsA) metabolism and on the activities of drug-metabolizing enzymes. Male Wistar
rats were used. The test rats (group T) were exposed to side-stream smoke from
cigarette for 2 h every day for 25 days. During the experimental period, the
excreted amount of AsA in the urine from group T was higher than that from the
control group (group C). At the end of the experimental period, the AsA content
of the plasma and tissues, the liver cytochrome P-450 content and the activities
of drug-metabolizing enzymes in group T were each higher than those in group C.
PMID- 9648214
TI - Correlation between the drinkability of beer and gastric emptying.
AB - A subjective evaluation of beer drinkability and the degree of stomach fullness
were found to correlate with the relaxed cross-sectional area of the pylorus
antrum measured by real-time ultrasonography. Five kinds of beer with a different
malt/adjuncts ratio and degree of attenuation were used. Each beer was given to 9
healthy volunteers at the rate of 3 ml/kg/15 min, and they each recorded the
degree of stomach fullness, desire to drink and tastiness every 30 min. With
increasing volume drunk, the degree of tastiness and desire to drink were
lowered, and the degree of stomach fullness raised. The relaxed cross-sectional
area of the pylorus antrum measured by an ultrasonic image analyzer every 30 min
was highly correlated with the degree of stomach fullness, tastiness of the beer,
and desire to drink (p = 0.0021, < 0.0001, 0.001). The beer giving the lowest
degree of stomach fullness was appraised to be tasty and highly drinkable. These
findings suggest that the rate of gastric emptying is one of the factors
determining the drinkability of beer, and that measurement of the relaxed cross
sectional area of the pylorus antrum is useful to evaluate stomach fullness
during beer drinking.
PMID- 9648215
TI - Isolation, characterization, and sugar chain structure of endoPG Ia, Ib and Ic
from Stereum purpureum.
AB - Three endopolygalacturonases (endoPG Ia, Ib, and Ic) were isolated from the
culture filtrate of Stereum purpureum, the causative fungus of apple silver-leaf
disease. Their properties, including specific activities, optimum pHs, thermal
stabilities, and kinetic parameters (K(m) and Vmax) were compared. Their
properties were very similar to one another except for the substrate specificity
and relative molecular mass. The sugar chains of endoPG Is were released by
hydrazinolysis, and one major sugar chain common to endoPG Is was isolated. The
pyridylamino sugar was characterized by a two-dimensional mapping method using
HPLC, and identified as a high mannose type N-linked sugar chain, Man alpha 1
6(Man alpha 1-3)Man alpha 1-6(Man alpha 1-3) Man beta 1-4 GlcNAc beta 1-4 GlcNAc
(designated as M5.1). Observation of the course of Western blot analysis for the
proteins from the culture filtrate with endoPG I antibodies showed that the
fungus secreted three endoPG Is into the culture broth during the growing period.
PMID- 9648216
TI - Cloning and characterization of the azurin iso-1 gene, concerned with the
electron transport chain involved in methylamine/methanol oxidation in the
obligate methylotroph Methylomonas sp. strain J.
AB - Two azurin-type blue copper proteins, which is concerned with the electron
transport chain involved in methylamine/methanol oxidation, have been found in
the obligate methylotroph Methylomonas sp. strain J. The azurin iso-1 gene was
cloned and sequenced to analyze the role in the electron transport chain. PCR
products synthesized with primers based on the N- and C-terminal amino acid
sequences of azurin iso-1 were used as probes for cloning. One complete open
reading frame (the azurin iso-1 gene) and one partial orf (orf1) were found in a
cloned Eco105I-HindIII fragment, pMAZ3, with a total of 1066 bp. The gene encoded
148 amino acid residues. The amino acid sequence after Ala-21, deduced from the
nucleotide sequence, was identical to that of the azurin iso-1 protein. The gene
was in a region separate from the mau gene cluster in the chromosome. Escherichia
coli expressed azurin iso-1. The results of northern blotting analysis suggested
that expression of the azurin iso-1 gene is regulated by a complex regulatory
network controlling oxidation of methylamine or methanol in this strain; for
example, copper ions affected the expression of the azurin iso-1 gene.
PMID- 9648217
TI - Isolation of Agrobacterium sp. strain KNK712 that produces N-carbamyl-D-amino
acid amidohydrolase, cloning of the gene for this enzyme, and properties of the
enzyme.
AB - Agrobacterium sp. strain KNK712, which produced N-carbamyl-D-amino acid
amidohydrolase (DCase) was isolated from soil. The bacterium had D-specific
hydantoinase activity also. Both enzymes are suitable for use in the production
of D-amino acids. The DCase gene from Agrobacterium sp. strain KNK712 was cloned
into Escherichia coli. The cloned DNA fragment contained one open reading frame,
predicted to encode a peptide of 304 amino acids, with a calculated molecular
weight of 34,285. The DCase gene was overexpressed under the control of the lac
promoter, and DCase accounted for 50% of the soluble protein in the cells. The
enzyme was purified and some properties were investigated. Both the optimum pH
and the pH that gave greatest stability were about pH 7.0. The optimum
temperature was 65 degrees C, and the enzyme was stable at 55 degrees C. The
enzyme had strict specificity toward N-carbamyl-D-amino acids, and was inhibited
by thiol reagents, Cu2+, Hg2+, Ag+, and ammonia.
PMID- 9648218
TI - Screening, characterization, and cloning of the gene for N-carbamyl-D-amino acid
amidohydrolase from thermotolerant soil bacteria.
AB - For the production of D-amino acids, thermotolerant bacteria producing N-carbamyl
D-amino acid amidohydrolase were isolated from soil by enrichment culture at 45
degrees C with N-carbamyl-D-amino acids as the sole nitrogen source. The enzyme
activities and substrate specificities of these strains were examined by the
resting cells reaction. One of the enzymes, produced by Pseudomonas sp. strain
KNK003A, was purified and characterized, and the amino acids of its N-terminal
region were sequenced. A DNA fragment containing the gene for a thermostable N
carbamyl-D-amino acid amidohydrolase was then cloned into Escherichia coli. The
gene encoded a peptide of 312 amino acids, with a calculated molecular weight of
35,000. The similarity of the deduced amino acid sequences of this enzyme and a
related enzyme from a mesophile, Agrobacterium sp. strain KNK712, was 60%. A
database was searched for similar sequences.
PMID- 9648219
TI - Sequence analysis by cloning of the structural gene of gassericin A, a
hydrophobic bacteriocin produced by Lactobacillus gasseri LA39.
AB - Gassericin A, a bacteriocin from Lactobacillus gasseri LA39, was purified to
homogeneity from the culturesupernatant mainly by reverse-phase chromatography.
The molecular weight of gassericin A was found to be 5,652 by mass analysis,
unlike the estimated 3,800 found by SDS-PAGE. However, when the purified
preparation was treated with lysylendopeptidase, it migrated as a single band to
5,600 with bacteriocin activity on SDS-PAGE. N- and C-terminal amino acids could
not be identified. The internal amino acid could be identified after gassericin A
was hydrolyzed with lysylendopeptidase. The DNA of the structural gene of
gassericin A was sequenced by cloning of the gene from chromosomal DNA with an
oligonucleotide probe. The structural gene of gassericin A was found on the
chromosomal DNA as an open reading frame encoding a protein composed of 91 amino
acids. The amino acid sequence of mature gassericin A was predicted to be 58
residues from the DNA sequence and results of mass analysis. These results
suggested that gassericin A has a closed circular structure with N- and C
terminals linked. Gassericin A is a hydrophobic class II bacteriocin; it was 98%
identical with acidocin B produced by Lactobacillus acidophilus M46.
PMID- 9648220
TI - Identification of deoxy-D-fructosyl phosphatidylethanolamine as a non-enzymic
glycation product of phosphatidylethanolamine and its occurrence in human blood
plasma and red blood cells.
AB - The amino-carbonyl reaction (Maillard reaction), also known as glycation, of egg
yolk phosphatidylethanolamine (PE) was induced by incubating PE (50 mg/ml) with D
glucose (222 mM) in a methanol medium containing 2,6-ditert-butyl-p-cresol as an
antioxidant at 37 degrees C for 4 days. The resultant product, glycated PE (gPE),
was then isolated from the reaction mixture by two-step normal and reversed-phase
high-performance liquid chromatography with UV diode array detection and was
characterized as having a 1:1:1 elemental ratio of phosphorus:nitrogen:sugar. The
Fourier transform-nuclear magnetic resonance spectrum and infrared absorbance
spectrum indicate the isolated gPE to have been deoxy-D-fructosyl PE, which is an
Amadori product of PE. The fast atom bombardmentmass spectrometric data for the
glycation product of authentic dioleoyl PE (1,2-di-9-octadecenoyl-sn-glycero-3
phosphoethanolamine) show that the molecular weight of gPE corresponds to that of
glucose-conjugated PE in the form of an Amadori product. This Amadori product
formation was also confirmed in PE/phosphate buffer dispersions and in
phosphatidylcholine-PE liposome/phosphate buffer suspensions in the presence of D
glucose at 37 degrees C. gPE was degraded by phospholipase A2, C and D. Freshly
spiked blood plasma and red blood cells (RBC) from nomal human volunteers
contained substantial levels of gPE, the concentration corresponding to at least
9 mol% of PE. Remarkable formation of gPE, up to 15-45 mol% of PE in human blood
plasma and RBC, was further confirmed by prolonged incubation with 5-45 mM D
glucose. The gPE formation in RBC was found to be proportional to the glycated
hemoglobin formation.
PMID- 9648221
TI - Effects of rapessed oil on activity of methylmalonyl-CoA carboxyltransferase in
culture of Streptomyces fradiae.
AB - To investigate why more tylosin was produced when Streptomyces fradiae T1558 was
cultured in a rapeseed oil medium than in a glucose or starch medium, we measured
the activity of methylmalonyl-CoA carboxyltransferase (EC 2.1.3.1) and
intracellular propionic acid. The activity of the enzyme, which catalyzes the
formation of the precursor of tylosin, protylonolide, was 0.19 U/mg protein in 5
days of culture in rapeseed oil medium, which was 2.5- and 1.3-fold that with the
glucose or starch medium, respectively. The intracellular propionic acid
concentration was 1.2 g/g of dry weight, which was 4.3- and 2.1-fold that with
the glucose or starch medium, respectively. The addition of propionic acid
increased tylosin production in batch culture: when 0.2 g/l (final concentration)
propionic acid was added to the glucose medium, 3.8 g/l tylosin was produced in
10 days of culture, 4.7-fold the amount without propionic acid. These findings
suggest that in glucose medium, intracellular propionic acid is a limiting factor
because of the low activity of methylmalonyl-CoA carboxyltransferase of the
tylosin biosynthesis pathway.
PMID- 9648222
TI - Liberation of phospholipids from Z-disks of chicken skeletal muscle myofibrils by
0.1 mM calcium ions: weakening mechanism for Z-disks during post-mortem aging of
meat.
AB - Weakening of the Z-disks of skeletal muscle myofibrils contributes to the
tenderization of meat during post-mortem aging. To elucidate the weakening
mechanism, we compared Z-disks weakened by post-mortem aging of chicken breast
muscle with those of myofibrils treated with a solution containing 0.1 mM CaCl2
and 1 microM calpastatin domain I. In both cases, the Z-disks were weakened with
a corresponding liberation of their constituent phospholipids (PLs). The
liberation of PLs specific to 0.1 mM calcium ions was minimal at pH 6.5 and
maximal at 35 degrees C together with the Z-disk weakening. Binding of calcium
ions to PLs in the Z-disks was determined by 45Ca-autoradiography. Acidic PLs
were strongly radioactive and neutral PLs were appreciably radioactive. It is
very probable that acidic PLs would bind electrostatically to alpha-actinin under
physiological conditions, and that this interaction would be broken by the
binding of calcium ions at 0.1 mM to PLs, resulting in the partial liberation of
PLs from Z-disks. We conclude, therefore, that the liberation of PLs by the
binding of 0.1 mM calcium ions was the main cause for Z-disk weakening during the
post-mortem aging of chicken.
PMID- 9648223
TI - Deterioration of connectin/titin and nebulin filaments by an excess of protease
inhibitors.
AB - We studied the effect of protease inhibitors at a high concentration on connectin
and nebulin filaments in myofibrils. Calpastatin domain I at 0.1 mM bound to
connectin and nebulin filaments, and deteriorated their physico-chemical
properties; the calcium-binding ability of connectin and nebulin filaments was
suppressed, the susceptibility of both filaments to trypsin was markedly
decreased, and the resting tension of mechanically skinned fibers was increased
by 2.5 times that of the control at a sarcomere length of 3.6 microns. This
indicates that the connectin filaments were made more rigid. The same phenomenon
was observed from the treatment of skinned fibers with 1 mM leupeptin whose
resting tension was increased to 2 times the control value. Microscopically, both
protease inhibitors induced dense aggregation and disappearance of the regular
striation of myofibrils due to their non-specific binding to many myofibrillar
proteins. The use of excess calpastatin domain I and leupeptin should therefore
be avoided in physiological and biochemical studies on connectin and nebulin
filaments, as well as on myofibrils.
PMID- 9648224
TI - Inhibitory effects of lipid oxidation on the activity of plasma lecithin
cholesterol acyltransferase.
AB - We investigated the effects of free radical generation on the esterification of
cholesterol by lecithin-cholesterol acyltransferase (LCAT). A water-soluble free
radical initiator, 2,2'-azobis-amidinopropane dihydrochloride (AAPH), inhibited
the activity of plasma LCAT as a function of the incubation time after its
addition. When a small amount of oxidized HDL was added to plasma, LCAT activity
was dose-dependently inhibited. To identify the effects of HDL oxidation on LCAT
activity, a purified enzyme and cofactor in a vesicle solution (an artificial
substrate) were used. i) LCAT activity was inhibited by the oxidation of
substrate vesicles, this inhibition being related to the degree of oxidation. ii)
This inhibition was observed even if apolipoprotein A-I was not oxidized. iii)
Oxidized phosphatidylcholine, but not oxidized cholesterol, in the vesicles
affected LCAT activity. iv) The addition of 0-40% of oxidized vesicles to normal
substrate vesicles resulted in the activity of LCAT being inhibited in a dose
dependent manner. These results suggest that the esterification of cholesterol by
LCAT may be affected by the oxidation of substrate phosphatidylcholine via free
radical generation in the plasma.
PMID- 9648225
TI - Complexes of serine acetyltransferase and isozymes of cysteine synthase in
spinach leaves.
AB - Polyclonal antibodies against cysteine synthase (CSase; EC 4.2.99.8) isozymes 1,
2, and 3 were used for the detection of complexes of these isozymes with serine
acetyltransferase (SATase; EC 2.3.1.30). SATase was partially purified and found
to complex with these isozymes by western blotting and immunotitration. When the
complexes were treated with a high concentration of O-acetyl-L-serine, they did
not dissociate. However, some complexes with CSase 1 or 3 dissociated when left
for 24 h at 4 degrees C. Results of western blotting on SDS-PAGE showed that
CSase 2 complexed with SATase. CSases 1, 2, and 3 all could complex with SATase,
but the tightness of the bond differed.
PMID- 9648226
TI - Direct formation of human interleukin-11 by cis-acting system of plant virus
protease in Escherichia coli.
AB - To produce a large amount of recombinant proteins in Escherichia coli, we
constructed a unique cis-acting expression system using a plant virus protease.
This new expression system could directly produce recombinant proteins, that had
a biologically active form. A gene of nuclear inclusion-a (NIa), which had a
specific amino acid sequence, was fused with a foreign protein gene at the same
protein reading frame. One of the NIa-specific cleavage amino acid sequences, Gln
Ala, was also contained at the protein-protein junction. In the case of human
interleukin-11 (hIL-11), a 23-kDa specific signal band was obtained from
recombinant bacteria. N-terminal sequencing of the 23-kDa protein showed that NIa
specifically cleaved the fusion protein at Gln-Ala, producing Ala-hIL-11.
Furthermore, we could produce the mature rhIL-11 by extending the culture time.
This 23-kDa protein had the same biological activity as hIL-11 in a mouse
plasmacytoma, T1165. Combined with fermentation control, we produced mature rhIL
11 in E. coli.
PMID- 9648227
TI - Chemical modifications of momordin-a and luffin-a, ribosome-inactivating proteins
from the seeds of Momordica charantia and Luffa cylindrica: involvement of
His140, Tyr165, and Lys231 in the protein-synthesis inhibitory activity.
AB - Effects of chemical modifications on the protein-synthesis inhibitory (PSI)
activities of momordin-a and luffin-a were investigated. Treatment with a 50-fold
excess of diethylpyrocarbonate at pH 6.5 modified one histidine residue in
momordin-a and luffin-a and reduced their PSI activities to 10% and 8.3%,
respectively. Modifications with a 20-fold excess of KI3 at pH 7.0 at 0 degree C
greatly reduced their PSI activities to 10% by iodination of nearly one tyrosine
residue. The PSI activity of momordin-a was rapidly reduced to 6.4% by the
modification of one lysine residue with trinitrobenzensulfonic acid as in the
case of luffin-a reported previously. By analyses of the tryptic peptides from
the modified momordin-a and luffin-a, the modified residues were identified as
His140, Tyr165, and Lys231. Furthermore, the amounts of three modified momordin-a
binding to rat liver ribosomes were reduced to about half or less than half of
that of native momordin-a. From these results, it was suggested that His140,
Tyr165, and Lys231 are highly exposed on the surface of momordin-a and luffin-a
molecules and are involved in their PSI activities, probably by binding to
ribosomes.
PMID- 9648228
TI - Low sucrase activity in the small intestine of a senescence-accelerated strain of
mouse, SAMP1.
AB - The small intestinal sucrase activity in a senescence-accelerated strain of
mouse, SAMP1, was significantly lower than that in other strains, including its
control strain, SAMR1. In contrast, the activity of isomaltase, which usually
associates with sucrase to form a complex enzyme (SI complex), in SAMP1 was
comparable to that in other strains. Thus, the ratio of the sucrase to isomaltase
activities (S/I ratio) in SAMP1 was very low (about 0.15), compared with that in
other strains (around 0.7). The S/I ratio in SAMP1 was abnormally low, even at a
young age, indicating that senescence did not result in the low sucrase activity.
Western blot analysis suggests that a large part of the isomaltase subunit
occurred alone without the association of the sucrase subunit in this strain. In
contrast, Northern blot analysis shows that the level of mRNA for the SI complex
in SAMP1 was comparable to that in SAMR1. When the pancreatico-biliary ducts were
ligated in SAMP1 to reduce the level of pancreatic proteases, a remarkable
increase was observed in the sucrase activity, whereas the isomaltase activity
was increased to a much smaller extent. This marked increase in sucrase activity
resulted in the S/I ratio increasing to 0.84 18 h after the ligation. These
results suggest the sucrase subunit of the SI complex to be abnormally unstable
against pancreatic proteases in SAMP1.
PMID- 9648229
TI - Antimutagenicity of flavones and flavonols to heterocyclic amines by specific and
strong inhibition of the cytochrome P450 1A family.
AB - We found the mechanism in flavonoids that can strongly suppress the mutagenicity
of one of the food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl
5H-pyrido[4,3-b]indole (Trp-P-2). The antimutagenicity was evaluated by IC50
value, the amount required for 50% inhibition of the mutagenicity of 0.1 nmol Trp
P-2, with Salmonella typhimurium TA98 strain in the presence of S9 mix. The
flavones and flavonols were two orders stronger as antimutagens that such
antimutagenic phytochemicals as chlorophylls and catechins. We had previously
found flavonoids to be a desmutagen to neutralize Trp-P-2 before or during attack
of DNA, because they had no effect on either the ultimate mutagenic form of Trp-P
2 (N-hydroxy-Trp-P-2) or the mutated cells. The desmutagenicity of the flavonoids
did not depend on the hydroxy number or position that should be associated with
antioxidative potency, and was also unaffected by the solubility of Trp-P-2 in
the assay solution. The inhibitory effect of the flavonoids on the metabolic
activation of Trp-P-2 to N-hydroxy-Trp-P-2 was almost in parallel with the
antimutagenic IC50 value, when determined with a Saccharomyces cerevisiae AH22
cell simultaneously expressing both rat cytochrome P450 1A1 and yeast reductase.
The Ki values of flavones and flavonols for the enzyme were less than 1 microM,
while the K(m) value of Trp-P-2 was 25 microM. The antimutagenicity of the
flavones and flavonols was thus concluded to be due to inhibition of the
activation process of Trp-P-2 by P450 1A1 to the ultimate carcinogenic form. They
were also able to act as antimutagens toward other indirect mutagens that were
activated by P450 1A1.
PMID- 9648230
TI - Rice bifunctional alpha-amylase/subtilisin inhibitor: characterization,
localization, and changes in developing and germinating seeds.
AB - A bifunctional alpha-amylase/subtilisin inhibitor (RASI) was purified to
electrophoretic homogeneity from rice (Oryza sativa L.) bran. Its molecular mass
was 21 kDa by SDS-PAGE and its isoelectric point was 9.05. Purified RASI
inhibited subtilisin Carlsberg strongly and inhibited alpha-amylase from
germinating rice seeds weakly. It inhibited rice alpha-amylase more than barley
alpha-amylase, and the inhibition of rice alpha-amylase was greater at higher
pHs. RASI did not inhibit trypsin, chymotrypsin, cucumisin, or mammalian alpha
amylase. The RASI was in the outermost part of the rice grain and its subcellular
site seemed to be aleurone particles in aleurone cells. SDS-PAGE and western
blotting showed that RASI was synthesized in the late milky stage in developing
seeds, and it remained fairly constant during the first 7 days of germination.
PMID- 9648231
TI - Salicylic acid induces a cytosolic Ca2+ elevation in yeast.
AB - Cytosolic free calcium ion concentration ([Ca2+]cyt) after a salicylic acid (SA)
stimulus was monitored in cells of the yeast Saccharomyces cerevisiae expressing
apoaequorin, which constitutes a Ca(2+)-sensitive luminescent protein, aequorin,
when combined with coelenterazine. SA induced a transient [Ca2+]cyt elevation
that was dependent on the concentration of SA and pH of the SA solution. The SA
induced [Ca2+]cyt elevation was not reduced in Ca(2+)-deficient medium,
suggesting that Ca2+ was mobilized from an intracellular Ca2+ store(s). Benzoic
acid, butyric acid and sorbic acid did not induced a [Ca2+]cyt elevation.
PMID- 9648233
TI - Effectiveness of polyclonal and monoclonal antibodies prepared for an immunoassay
of the etofenprox insecticide.
AB - Two polyclonal antibodies and three monoclonal antibodies specific to the
etofenprox insecticide were prepared from rabbits and mice, respectively. The
monoclonal antibodies were more reactive with etofenprox than the polyclonal
antibodies by C-ELISA. Monoclonal antibody cl 205-65 was found to be the most
tolerant to methanol, most highly reactive and most specific to etofenprox among
the antibodies tested.
PMID- 9648232
TI - Effect of magnetite on the hematocrit value in exsanguinated rats.
AB - Magnetite prepared by an enzyme-dependent reaction gradually released iron ion
into the acidic-to-neutral buffer solution. A preparatory experiment was
performed to examine the efficiency of magnetite as an iron supplement. Feeding
exsanguinated rats with being magnetite resulted in the hematocrit value being
recovered without any serious adverse effect on the digestive organs.
PMID- 9648234
TI - Affinity of antioxidative polyphenols for lipid bilayers evaluated with a
liposome system.
AB - We developed a method to measure the amounts of antioxidative polyphenols and
ubiquinones incorporated into the liquid bilayers of liposomes to estimate their
affinities for cell membranes. Results were expressed in terms of an "affinity
factor", calculated by division of the amount of compound incorporated by the
amount added to the liposomal solution. The results reflected dose-dependence of
the biological activities of the compound found in earlier in vitro experiments
with mammalian and bacterial cells.
PMID- 9648235
TI - Effects of vitamin B6 deficiency on cytokine levels and lymphocytes in mice.
AB - The effects of vitamin B6 (B6) deficiency on cytokine levels and proportions of
lymphocyte subsets in BALB/c mice were investigated. The proportion of
lymphocytes from the thymus and spleen of mice given no B6, that were CD4+ CD8- T
cells, was larger than in mice given B6, and the ratio of CD8+ to CD4+ T cells in
the thymus of mice given no B6 was lower. The concentrations of interleukin-5 and
-10 in spleen cells stimulated in vitro with concanavalin A were significantly
higher in the mice with B6 deficiency, as was their plasma corticosterone
concentrations. These results suggested that B6 is necessary to maintain cytokine
levels and lymphoid function in the thymus and spleen of mice.
PMID- 9648236
TI - Antimicrobial activity of a compound isolated from an oil-macerated garlic
extract.
AB - A compound showing antimicrobial activity was isolated from an oil-macerated
garlic extract by silica gel column chromatography and preparative TLC. On basis
of the results of NMR and MS analyses, it was identified as Z-4,5,9-trithiadeca
1,6-diene-9-oxide (Z-10-devinylajoene; Z-10-DA). Z-10-DA exhibited a broad
spectrum of antimicrobial activity against such microorganisms as gram-positive
and gram-negative bacteria and yeasts. The antimicrobial activity of Z-10-DA was
comparable to that of Z-ajoene, but was superior to that of E-ajoene. Z-10-DA and
Z-ajoene are different in respect of substitution of the allyl group by the
methyl group flanking a sulfinyl group. This result suggests that substitution by
the methyl group would also be effective for the inhibition of microbial growth.
PMID- 9648237
TI - Molecular cloning and expression patterns of Cu/Zn-superoxide dismutases in
developing soybean seeds.
AB - Assuming that the amount of superoxide radicals generated in vivo correlates with
the production of ergastic substances such as storage proteins, the coordinated
response of detoxication enzymes such as superoxide dismutases is largely
exploited to understand the self-defense systems of plant. Here we examined
expression of the genes for superoxide dismutases during seed development of
soybean. The cDNAs encoding a cytosolic copper/zinc form and an iron form of the
above enzyme have been cloned and then employed as probes, separately. Northern
blotting results suggested that both superoxide dismutase mRNAs are expressed at
the maximum level, preceding a developmental stage when mRNA encoding glycinin,
soybean 11S-storage protein, at the maximum.
PMID- 9648238
TI - Insecticidal and antifungal activities of aminorhodanine derivatives.
AB - Aminorhodanine (1) showed strong insecticidal activity against Culex pipiens
pallens and Musca domestica, with respective LD50 values of 0.21 microgram/insect
and 0.87 microgram/insect. Compound 1 had antifungal activity against Aspergillus
niger ATCC-16404, Trichophyton mentagrophytes IFO-32412, Candida albicans ATCC
10231, Hansenula anomala OPS-308 and Penicillium expansum IFO-8800. In
particular, 1 had potent antifungal activity against Aspergillus niger ATCC
16404, its minimal inhibitory concentration (MIC) being 6.25 micrograms/ml. Both
activities of 1 were much higher than those of rhodanine (4), suggesting that the
introduction of an amino group into N-3 of 4 plays an important role in the
biological activity of rhodanine-related compounds. On the other hand, N
acetylaminorhodanine (2) and N-benzoylaminorhodanine (3) did not show either
activity, suggesting that the free amino group at N-3 of 1 is closely related to
the inhibitory activity of rhodanine derivatives.
PMID- 9648239
TI - Thermostable neutral protease resembling thermolysin derived from Bacillus brevis
MIB001.
AB - A microbe producing a protease with strong thermostability that was released
extracellularly was isolated from soil. The isolate, MIB001, grew at from 15 to
51 degrees C and pH 5.1-8.8 and was tentatively identified as a strain of
Bacillus brevis. Rabbit antisera raised against a pure preparation of the
protease did not cross-react with thermolysin or neutral metalloprotease from
Bacillus stearothermophilus KP1236.
PMID- 9648240
TI - Interaction between the carboxyl-terminal heparin-binding domain of fibronectin
and (-)-epigallocatechin gallate.
AB - We have previously reported that (-)-epigallocatechin gallate (EGCg) inhibited
lung carcinoma cell adhesion to fibronectin (FN) and demonstrated its interaction
with FN. In the present work, we studied the interaction between thermolysin
fragments of FN and EGCg. An amino acid sequence analysis of the fragment bound
by EGCg-agarose provided its identification as a carboxyl-terminal heparin
binding domain. Thus, the inhibition of cancer cell adhesion to FN by EGCg is not
caused by its direct binding to the cell-binding domain containing an Arg-Gly-Asp
sequence.
PMID- 9648241
TI - Features of Tri101, the trichothecene 3-O-acetyltransferase gene, related to the
self-defense mechanism in Fusarium graminearum.
AB - A structural gene of Tri101, which encodes trichothecene 3-O-acetyltransferase,
was isolated as a 3-kb XhoI-XbaI fragment from the trichothecene producer
Fusarium graminearum strain F15. The gene contained no introns, and the coding
region was 0.7-kb downstream of a putative UTP-ammonia ligase gene which
obviously is not related to the biosynthesis of trichothecenes. Tri101 was
expressed when T-2 toxin was added, but this induction was not dependent on the
expression level of Tri6, a transcription activator gene in the trichothecene
biosynthetic and regulatory gene cluster.
PMID- 9648242
TI - cDNA cloning, expression, and characterization of the human bifunctional ATP
sulfurylase/adenosine 5'-phosphosulfate kinase enzyme.
AB - A cDNA encoding the human bifunctional ATP sulfurylase/adenosine 5'
phosphosulfate (APS) kinase was cloned and sequenced. The enzyme contains an APS
kinase domain in its N-terminal portion and an ATP sulfurylase domain in its C
terminal portion. Recombinant full-length enzyme and its constituent APS kinase
and ATP sulfurylase domains were individually expressed, purified, and shown to
have their respective enzymatic activities.
PMID- 9648243
TI - Measurement of long-range carbon-carbon coupling constants in a uniformly
enriched complex polysaccharide.
AB - A quantitative coherence transfer scheme for 1H-detected measurement of long
range carbon-carbon coupling constants in NMR spectra of complex carbohydrates is
described. It is applied to a uniformly highly 13C-enriched monosaccharide and to
a complex cell wall polysaccharide from Streptococcus mitis J22 having seven
distinct sugars in the repeating subunit. Coupling values within the ring were
compared to published values for monosaccharides to demonstrate the validity of
the method. An attempt was made to relate coupling constants between carbon atoms
across the glycosidic linkage to the dihedral angles of a recently published
flexible model for the polysaccharide which is based on 3JCH data. The
experimental coupling constants do not agree with any single conformation
demonstrating that the repeating subunit of the polysaccharide must be flexible.
This conclusion is in accord with results of molecular modeling nuclear
Overhauser effect and 3JCH data.
PMID- 9648244
TI - Synthesis of aryl 3'-sulfo-beta-lactosides as fluorogenic and chromogenic
substrates for ceramide glycanases.
AB - We have previously reported that 4-methylumbelliferyl 6'-O-benzyl-beta-lactoside
(2) is a useful substrate for a fluorometric assay of ceramide glycanase (CGase)
(L.-X. Wang, N. V. Pavlova, S.-C. Li, Y.-T. Li and Y. C. Lee, Glycoconjugate J.,
13 (1996) 359-365). The introduction of a 6-O-benzyl group at the terminal Gal
efficiently protected the substrate from its hydrolysis by exo-galactosidase,
permitting the assay of CGase in crude biological materials. However, a drawback
of this substrate is its low water-solubility and relatively high Km (at a mM
level). Introduction of a sulfate group into 4-methylumbelliferyl beta-lactoside
(1) led to the formation of 4-methylumbelliferyl 3'-O-sulfo-beta-lactoside (3),
which was found to be a more effective substrate than 2. Moreover, the presence
of a 3'-O-sulfate group not only increases the water solubility tremendously, but
also protects the substrate from cleavage by exo-beta-galactosidase as the 6'-O
benzyl group in 2 does. In addition to the fluorogenic substrate (3), two
sulfated chromogenic substrates, N-tetradecanoyl-4-O(3'-sulfo-beta-lactosyl)-3
nitro-L-tyrosine methyl ester (9) and 2-N-(tetradecanoylamino)-4-nitro-phenyl 3'
sulfo-beta-lactoside (12), were synthesized and their suitability for a
photometric assay of CGase was evaluated. Substrates 9 and 12, with a long fatty
acid chain attached to the aglycon part, have a Km value close to that of the
natural substrate GM1 (at a microM level).
PMID- 9648245
TI - Synthesis of 1-N-[(2S,4S)- and (2S,4R)-5-amino-4-fluoro-2
hydroxypentanoyl]dibekacins (study on structure-toxicity relationships).
AB - (2S,4S)- and (2S,4R)-5-azido-2-O-benzyl-4-fluoro-2-hydroxypentanoic acids (15 and
19) have been prepared from L-malic acid (1), and coupled to the H2N-1 group of
3,2',6'-tris(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)dibekacin (23), to give,
after reduction and deblocking, 1-N-[(2S,4S)- and (2S,4R)-5-amino-4-fluoro-2
hydroxypentanoyl]dibekacins (26 and 27). The fluorinated arbekacin analogs showed
almost the same antibacterial activities as that of arbekacin, but lower
toxicity. Comparison of the toxicity between 26 (and 27) and the arbekacin
analogs (28-30) with change of the 1N-side-chain indicates that the observed
decrease in toxicity was a function of the chain length rather than the
introduction of fluorine.
PMID- 9648246
TI - Synthesis of the unique trisaccharide repeating unit, isolated from
lipopolysaccharides Rhizobium leguminosarum bv. trifolii 24, and its analogue.
AB - The synthesis of trisaccharide: 6-d-alpha-L-Talp(1-->2)-alpha-L-Rhap(1-->5)-DHA,
and its analogue: 6-d-alpha-L-Talp(1-->2)-beta-L-Rhaf(1-->5)DHA is described. In
the first step a disaccharide, composed of 6-d-L-Talp and L-Rhap was obtained.
This, in turn, was converted to the corresponding 1-trichloroacetimidate and
coupled with DHA alcohol to afford the required trisaccharide. Its analogue was
achieved by the conversion of the above disaccharide to the glycosyl bromide,
involving the rhamnopyranose ring scission, followed by condensation with DHA in
Koenigs-Knorr procedure.
PMID- 9648247
TI - Enzymatic synthesis of N-linked oligosaccharides terminating in multiple sialyl
Lewis(x) and GalNAc-Lewis(x) determinants: clustered glycosides for studying
selectin interactions.
AB - Galactosyltransferase, sialyltransferase, and fucosyltransferase were used to
create a panel of complex oligosaccharides that possess multiple terminal sialyl
Le(x) (NeuAc alpha 2-3Gal[Fuc alpha 1-3] beta 1-4GlcNAc) and GalNAc-Le(x)
(GalNAc[Fuc alpha 1-3]beta 1-4GlcNAc). The enzymatic synthesis of tyrosinamide
biantennary, triantennary, and tetraantennary N-linked oligosaccharides bearing
multiple terminal sialyl-Le(x) was accomplished on the 0.5 mumol scale and the
purified products were characterized by electrospray MS and 1H NMR. Likewise,
biantennary and triantennary tyrosinamide oligosaccharides bearing multiple
terminal GalNAc-Le(x) determinants were synthesized and similarly characterized.
The transfer kinetics of human milk alpha 3/4-fucosyltransferase were compared
for biantennary oligosaccharide acceptor substrates possessing Gal beta 1
4GlcNAc, GalNAc beta 1-4GlcNAc, and NeuAc alpha 2-3Gal beta 1-4GlcNAc which
established NeuAc alpha 2-3Gal beta 1-4GlcNAc as the most efficient acceptor
substrate. The resulting complex oligosaccharides were chemically tethered
through the tyrosinamide aglycone to the surface of liposomes containing
phosphatidylthioethanol, resulting in the generation of glycoliposomes probe
which will be useful to study relationships between binding affinity and the
micro- and macro-clustering of selectin ligand.
PMID- 9648248
TI - Synthesis of the tetrasaccharide repeating unit of the K-antigen from Klebsiella
type 57.
AB - Starting from D-galactose and D-mannose two disaccharide blocks, namely 2
(trimethylsilyl)-ethyl 2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl-(1-->4)-6-O
(4-methoxybenz yl)- beta-D-galactopyranoside and ethyl 2,3,4,6-tetra-O-benzyl
alpha-D-mannopyranosyl-(1-->3)-4-O-acetyl- 2,6-di-O-benzoyl-1-thio-beta-D
galactopyranoside, were synthesized which were then allowed to react, in the
presence of dimethyl(methylthio)sulfonium triflate to give a tetrasaccharide
derivative. This compound was converted to 2-(trimethylsilyl)ethyl 2,3,4,6-tetra
O-benzyl-alpha-D- mannopyranosyl-(1-->3)-4-O-acetyl-2,6-di-O-benzoyl-beta-D
galactopyranos yl- (1-->3)-[2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl-(1-
>4)]-tert-but yl (2-O-acetyl-beta-D-galactopyranosid)uronate which, on treatment
with sodium methoxide followed by hydrogenolysis, afforded the methyl [2
(trimethylsilyl)ethyl glycosid]uronate of the tetrasaccharide repeating unit of
the K-antigen from Klebsiella type 57.
PMID- 9648249
TI - Examination of number-average degree of polymerization and molar-based
distribution of amylose by fluorescent labeling with 2-aminopyridine.
AB - Suitable conditions for the fluorescent labeling of the reducing residue of
amylose with 2-aminopyridine were examined. Amylose of up to 38.5 nmol was
labeled with a constant labeling efficiency. The same efficiencies were obtained
for amyloses having a number-average degree of polymerization (dpn) of 521-4400.
The analysis of labeled amylose on size-exclusion HPLC with refractive index and
fluorescence detection enabled the determination of dpn and dp distribution on a
molar basis. The analysis of eight amylose specimens from seven botanical sources
(potato, sweet potato, barley, wheat, indica rice, japonica rice, and maize) gave
dpn values in good agreement with those determined by a conventional colorimetric
method. The molar-based distributions of these amyloses were characteristic of
botanical source and revealed the presence of several molecular species with
different dp not detectable in the distribution on a weight basis. Small amyloses
with a dp less than 10(3) were predominant in the cereals while amyloses with a
dp over 10(3) were predominant in the tubers, suggesting a difference in the
biosynthetic process determining the dp distribution of amylose between cereals
and tubers.
PMID- 9648250
TI - Regioselective syntheses of sulfated polysaccharides: specific anti-HIV-1
activity of novel chitin sulfates.
AB - A novel and convenient method for the regioselective syntheses of sulfated
analogs of chitin and chitosan is described in relation to studies on structure
biological activity. Fully protected, soluble derivatives of chitosan were found
to be useful intermediates for the syntheses of a novel class of sulfated
polysaccharides, 2-acetamido-2-deoxy-3-O-sulfo-(1-->4)-beta-D-glucopyranan (3
sulfate, 3S, 4) and (1-->4)-2-deoxy-2-sulfoamido-3-O-sulfo-(1-->4)-beta-D
glucopyranan (2,3-disulfate, 23-S, 3). These compounds were tested for their
activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting blood
coagulation. The results reveal that the selective sulfation at O-2 and/or O-3
affords potent antiretroviral agents showing a much higher inhibitory effect on
the infection of AIDS virus in vitro than that by the known 6-O-sulfated
derivative (6-sulfate, 6S). Moreover, the 23-S product completely inhibited the
infection of AIDS virus to T lymphocytes at concentrations as low as 0.28
microgram/mL without significant cytotoxicity. The regioselective introduction of
sulfate group(s) at O-2 and/or O-3 had little effect on generating anticoagulant
activity, whereas 6-O-sulfated chitin strongly inhibits blood coagulation. These
results suggest that the specific interaction of these new types of chitin
sulfates with gp 120 of the AIDS virus depends significantly on the sites of
sulfation rather than on the total degree of substitution on sugar residues.
PMID- 9648251
TI - Structural analysis of oligosaccharide-alditols released by reductive beta
elimination from oviducal mucins of Rana dalmatina.
AB - The O-linked oligosaccharides of the jelly coat surrounding the eggs of Rana
dalmantina were released by alkaline borohydride treatment. Low-molecular-mass,
monosialyl oligosaccharide-alditols were isolated by anion-exchange
chromatography and fractionated by consecutive normal-phase high-performance
liquid chromatography on a silica-based alkylamine column. The structures of the
oligosaccharide-alditols were determined by 400-MHz 1H-NMR spectroscopy in
combination with matrix assisted laser desorption ionization-time of flight
analysis. The five structures were identified range in size from trisaccharides
to hexasaccharides, possessing a core consisting of Gal(beta 1-3)GalNAc-ol (core
type 1). Novel oligosaccharide-alditols are: [formula: see text] The carbohydrate
chains isolated from Rana dalmatina are different from those found in other
amphibian species, in which the presence of species-specific material has been
characterized. Since the role of carbohydrates appears more and more apparent
during the fertilization process, the biodiversity of the O-linked
oligosaccharides could support such a biological role.
PMID- 9648252
TI - Biochemical and catalytic properties of an endoxylanase purified from the culture
filtrate of Thermomyces lanuginosus ATCC 46882.
AB - An endoxylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) from the culture
filtrates of T. lanuginosus ATCC 46882 was purified to homogeneity by DEAE
Sepharose and Bio-Gel P-30 column chromatographies. The purified endoxylanase had
a specific activity of 888.8 mumol min-1 mg-1 protein and accounted for
approximately 30% of the total protein secreted by this fungus. The molecular
mass of native (non-denatured) and denatured endoxylanase were 26.3 and 25.7 kD
as, respectively. Endoxylanase had a pI of 3.7 and was optimally active between
pH 6.0-6.5 and at 75 degrees C. The enzyme showed > 50% of its original activity
between pH 5.5-9.0 and at 85 degrees C. The pH and temperature stability studies
revealed that this endoxylanase was almost completely stable between pH 5.0-9.0
and up to 60 degrees C for 5 h and at pH 10.0 up to 55 degrees C for 5 h. Thin
layer chromatography (TLC) analysis showed that endoxylanase released mainly
xylose (Xyl) and xylobiose (Xyl2) from beechwood 4-O-methyl-D-glucuronoxylan, O
acetyl-4-O-methyl-D-glucuronoxylan and rhodymenan (a beta-(1-->3)-beta(1-->4)
xylan). Also, the enzyme released an acidic xylo-oligosaccharide from 4-O-methyl
D-glucuronoxylan, and an isomeric xylotetraose and an isomeric xylopentaose from
rhodymenan. The enzyme hydrolysed [1-3H]-xylo-oligosaccharides in an endofashion,
but the hydrolysis of [1-3H]-xylotriose appeared to proceed via
transglycosylation. since the xylobiose was the predominant product. Endoxylanase
was not active on pNPX and pNPC at 40 and 100 mM for up to 6 h, but showed some
activity toward pNPX at 100 mM after 20-24 h. The results suggested that the
endoxylanase from T. lanuginosus belongs to family 11.
PMID- 9648253
TI - Chemoenzymatic synthesis of carbohydrates.
PMID- 9648254
TI - Practical synthesis of 4-hydroxy-3-oxobutylphosphonic acid and its evaluation as
a bio-isosteric substrate of DHAP aldolase.
AB - An efficient four step synthesis of the title compound 4-hydroxy-3
oxobutylphosphonate (2) has been developed based on inexpensive 4-ethoxy-1
hydroxybutane-2-one using an Arbusow reaction (59% overall yield). Several
dihydroxyacetone-dependent aldolases having different stereospecificities were
tested for their acceptance of this phosphonomethyl substrate mimic as the aldol
donor. Individual enzymes belonging to both type I (Schiff base formation) and
type II (Zn2+ catalysis) mechanistic classes were found to catalyze the
stereoselective addition of 2 to simple aldehydes to provide bio-isosteric
analogs of sugar 1-phosphates in high yields. The lack of acceptance by specific
enzymes is discussed with regard to recent protein X-ray data.
PMID- 9648255
TI - Diastereoselective resolution of 6-substituted glycosides via enzymatic
hydrolysis.
AB - The diastereoselectivity of the enzymatic hydrolyses of 4-nitrophenyl 6-deoxy-6
methyl-(R)- and (S)-sulfinyl-beta-D-galactopyranoside (1a,b), 4-nitrophenyl 7
deoxy-D- and L-glycero-beta-D-galacto-heptopyranoside (2a,b) and 4-nitrophenyl
6,7-anhydro-D- and L-glycero-beta-D-galacto-heptopyranoside (3a,b) was
investigated using a range of crude glycosidase preparations. It was shown that
the enzymes display a high degree of discrimination between diastereomers thereby
demonstrating the utility of glycosidases for the diastereomeric resolution of
unnatural 6-substituted monosaccharide derivatives.
PMID- 9648256
TI - Trisaccharide synthesis by glycosyl transfer from p-nitrophenyl beta-D-N
acetylgalactosaminide on to disaccharide acceptors catalysed by the beta-N
acetylhexosaminidase from Aspergillus oryzae.
AB - The beta-N-acetylhexosaminidase from Aspergillus oryzae catalysed the transfer of
beta-D-N-acetylgalactosaminyl residues from p-nitrophenyl beta-D-N
acetylglucosaminide on to disaccharide acceptors consisting of thioethyl
glycosides of alpha-D-Glc-(1-->4)-beta-D-Glc, beta-D-Glc-(1-->4)-beta-D-Glc and
beta-D-Glc-(1-->6)-beta-D-Glc. The principle of 'anomeric control' was
exemplified by the results which showed that an alpha-linkage between the units
of the acceptor favoured exclusively the formation of a new (1-->4)-linkage,
whereas the beta-configuration in the acceptor led to a mixture of (1-->4)- and
(1-->3)-linked products, as observed for simple glycosides of monosaccharide
acceptors. With the thioethyl beta-lactoside as acceptor, beta-D-Gal-(1-->6)-beta
D-Gal-(1-->4)-beta-D-GlcSEt was formed, owing to the action of residual beta-D
galactosidase activity in the N-acetylhexosaminidase on the thioethyl beta
lactoside acting as both donor and acceptor.
PMID- 9648257
TI - Regioselectivity of the enzymatic transgalactosidation of D- and L-xylose
catalysed by beta-galactosidases.
AB - The regioselectivity of enzymatic transgalactosidation depends on the source of
the beta-galactosidase used. When the galactosyl acceptor only contains secondary
hydroxyl groups, e.g., D- or L-xylose, it is possible to find an enzyme that
catalyses preferentially the synthesis of any of the three regioisomers 4-, 3-
and 2-O-beta-D-galactopyranosyl-D-xylose (1, 2 and 3, respectively) or 4-, 3- and
2-O-beta-D-galactopyranosyl-L-xylose (4, 5 and 6, respectively). Enriched
mixtures in 1, 2 or 3 were obtained using beta-galactosidases from Escherichia
coli, bovine testes or Aspergillus oryzae, respectively, by transgalactosidation
reaction of O-nitrophenyl-beta-D-galactopyranoside and D-xylose, and enriched
mixtures in 4, 5 or 6 were obtained in a similar way using beta-galactosidases
from Aspergillus oryzae, lamb small-intestine (intestinal lactase-phloridzin
hydrolase) or Saccharomyces fragilis, respectively, using L-xylose as acceptor.
PMID- 9648258
TI - Enzymatic synthesis, isolation, and analysis of novel alpha- and beta-galactosyl
cycloisomalto-octaoses.
AB - Novel branched cycloisomalto-octaoses (CI8s) were enzymatically synthesized by
transgalactosylation with alpha-galactosidase from coffee bean and beta
galactosidase preparations from Penicillium multicolor and Bacillus circulans,
using melibiose and lactose as donor substrates, and CI8 which is a cyclic
homogeneous oligosaccharide composed of eight glucose units bound by alpha-(1-
>6)-linkages, as an acceptor. alpha-Galactosyl-CI8s and beta-galactosyl-CI8s
obtained were isolated and purified by HPLC. Their structures were elucidated by
matrix-assisted laser desorption ionization time-of-flight mass spectrometry
(MALDITOFMS) and NMR spectroscopy.
PMID- 9648259
TI - Chemoenzymatic synthesis of the branched oligosaccharides which correspond to the
core structures of N-linked sugar chains.
AB - Synthetic routes are described to a partial structure common to all high mannose
type sugar chains and complex-type sugar chains based on a chemoenzymatic
strategy which incorporates, (a) enzymatic synthesis of oligosaccharide blocks
using glycosidases, and (b) chemical synthesis of the branching oligosaccharides
via regioselective coupling. All reaction products correspond to key
intermediates necessary for the construction of N-linked oligosaccharides and we
have synthesized the branched tetra-manno-oligosaccharide high mannose-type sugar
chain and the branched hexa-oligosaccharide complex-type sugar chain using this
simple and direct method.
PMID- 9648260
TI - Chemoenzymatic synthesis of a novel glycopeptide using a microbial
endoglycosidase.
AB - The chemoenzymatic synthesis of a glycopeptide by chemical synthesis of N
acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide is
described. We synthesized glycosylated Peptide T which blocks infection of human
T cells by human immunodeficiency virus. The first step of the chemoenzymatic
method is the solid-phase chemical synthesis of N-acetylglucosaminyl Peptide T
(Ala-Ser-Thr-Thr-Thr-Asn(GlcNAc)-Tyr-Thr) with an N-acetylglucosamine moiety
bound to the asparaginyl residue by a solid-phase method. This product was
prepared in high yield by the dimethylphosphinothioic mixed anhydride method
without protecting the hydroxyl functions of the sugar moiety using Fmoc-N
acetylglucosaminyl asparagine instead of Fmoc-asparagine. The second step was
transglycosylation of complex type oligosaccharide to N-acetylglucosaminyl
Peptide T by a microbial endoglycosidase. The endo-beta-N-acetylglucosaminidase
of Mucor hiemalis transfer the oligosaccharide of human transferrin glycopeptide
to N-acetylglucosaminyl Peptide T. The transglycosylation product was confirmed
to be the glycosylated Peptide T with a sialo biantennary complex type
oligosaccharide by mass spectrometry. The glycosylated Peptide T was highly
stable against proteolysis in comparison to native Peptide T and N
acetylglucosaminyl Peptide T.
PMID- 9648261
TI - Chemoenzymatic synthesis of a sialylated diantennary N-glycan linked to
asparagine.
AB - A partial structure of many glycoproteins, a glycosylated asparagine carrying a
complex type undecasaccharide N-glycan (Neu5Ac(alpha 2-6)Gal(beta 1-4)GlcNAc(beta
1-2)Man alpha 1-3) [Neu5Ac(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-2)Man(alpha 1
6)]Man(beta 1-4) GlcNAc(beta 1-4)GlcNAc-Asn) was obtained by total synthesis. As
a starting material served a chemically synthesized diantennary heptasaccharide
azide which was deprotected in a three-step sequence in high yield. The reduction
of the anomeric azide was accomplished with propanedithiol in methanol
ethyldiisopropylamine. Coupling of the glycosyl amine to an activated aspartic
acid gave the benzyl protected asparagine conjugate. After removal of the six
benzyl functions the resulting free heptasaccharide asparagine was elongated
enzymatically in the oligosaccharide part. The use of beta-1,4
galactosyltransferase and alpha-2,6-sialytransferase in the presence of alkaline
phosphatase allowed the efficient transfer of four sugar units to the acceptor
resulting in a full length N-glycan, a sialyated diantennary undecasaccharide
asparagine of the complex type.
PMID- 9648262
TI - Chemoenzymatic synthesis of dendritic sialyl Lewis(x).
AB - Traditional structure activity relationship studies (SAR) have led to the
development of numerous sialyl Lewis(x) analogs in the search for potential
antiinflammatory agents. However, these methods do not take into account cluster
or multivalent effects. Reported herein is the chemoenzymatic synthesis of di-,
tetra-, and octa-valent sLe(x) ligands scaffolded on dendrimers. Hypervalent L
lysine cores with covalently attached 2-acetamido-2-deoxy-D-glucose (N
acetylglucosamine, GlcNAc) residues were chemically prepared and enzymatically
transformed into sLe(x) containing dendrimers so that multivalency, and its role
in selectin-sLe(x) interactions may be evaluated. This work constitutes another
successful enzymatic synthesis of sLe(x) and represents the first example of
GlcNAc elongation on a synthetic dendrimer scaffold. These sLe(x) dendrimers are
currently being investigated as selectin antagonists.
PMID- 9648263
TI - High performance polymer supports for enzyme-assisted synthesis of
glycoconjugates.
AB - Efficient and practical methodology for the construction of carbohydrates,
including oligosaccharide derivatives and sphingoglycolipids, was established on
the basis of a water-soluble polymer supports having unique linkers that can be
cleaved by specific conditions. Novel glycomonomers for the construction of
polymer supports were synthesized and copolymerized with acrylamide to give three
types of water-soluble glycopolymers having primer sugars through the specific
linkers containing (i) p-substituted benzyl group, (ii) L-phenylalanine residue,
and (iii) ceramide-mimetic L-serine derivative, respectively. These glycopolymers
were employed for sugar elongation reactions with glycosyl transferases such as
GlcNAc beta 1,4-galactosyl transferase, beta Gall-->3/4GlcNAc alpha-2,6-sialyl
transferase, and beta Gall-->3/4GlcNAc alpha-2,3-sialyl transferase in the
presence of each sugar nucleotide as glycosyl donor to afford polymers having N
acetyllactosamine, sialyl alpha-(2-->6) N-acetyllactosamine, and sialyl alpha-(2-
>3) lactose residues in excellent yield. Subsequent hydrogenolysis, hydrolysis
with alpha-chymotrypsin, or transglycosylation to ceramide with ceramide
glycanase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl alpha
(2-->6) N-acetyllactosamine derivative having a terminal amino group, and
ganglioside GM3 in high yield.
PMID- 9648264
TI - Enzyme-assisted synthesis of Asn-linked diantennary oligosaccharides occurring on
glycodelin A.
AB - The preparation of a series of sialylated and fucosylated N,N'
diacetyllactosediamine-type diantennary glycopeptides is reported. By sequential
enzymatic action of jack bean beta-galactosidase, snail beta 4-N-acetyl
galactosaminyltransferase, bovine colostrum alpha 6-sialyltransferase and human
milk alpha 3-fucosyltransferase, a diantennary glycopeptide obtained from asialo
fibrinogen was converted at a 5-mumol scale to a series of structures occurring
on the glycoprotein glycodelin A, which potentially inhibit human sperm-egg
binding.
PMID- 9648265
TI - Acceptor hydroxyl group mapping for calf thymus alpha-(1-->3)
galactosyltransferase and enzymatic synthesis of alpha-D-Galp-(1-->3)-beta-D-Galp
(1-->4)-beta D-GlcpNAc analogs.
AB - The epitope of the acceptor substrate for alpha-(1-->3)-galactosyltransferase
from calf thymus has been mapped by using a series of mono-deoxygenated and mono
O-alkylated Type II (beta-D-Ga1p-(1-->4)-beta-D-G1cpNAc) disaccharides. The 4-OH
group of the beta-D-galactopyranosyl residue is a key polar group essential for
glycosyl transfer, tolerating neither deoxygenation nor O-alkylation.
Substitution at positions 6 and 6' by a variety of polar alkyl substituents was
readily tolerated, allowing the preparative enzymatic synthesis of a series of
trisaccharide derivatives carrying polar substituents on each of these hydroxyl
groups. These new analogs are potential inhibitors of Clostridium difficile toxin
A and of a human anti-alpha-Gal antibody.
PMID- 9648266
TI - Enzymatic synthesis of site-specifically (alpha 1-3)-fucosylated polylactosamines
containing either a sialyl Lewis (x), a VIM-2, or a sialylated and internally
difucosylated sequence.
AB - By using two different reaction pathways, we generated enzymatically three
sialylated and site-specifically alpha 1-3-fucosylated polylactosamines. Two of
these are isomeric hexasaccharides Neu5Ac(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1
3)Gal(beta 1-4)[Fuc(alpha 1-3)] GlcNAc and Neu5Ac(alpha 2-3)Gal(beta 1
4)[Fuc(alpha 1-3)]GlcNAc(beta 1-3)Gal(beta 1-4) GlcNAc, containing epitopes that
correspond to VIM-2 and sialyl Lewis (x), respectively. The third one,
nonasaccharide Neu5Ac(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1
4)[Fuc(alpha 1-3)] GlcNAc(beta 1-3)Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc, is a
sialylated and internally difucosylated derivative of a trimeric N
acetyllactosamine. All three oligosaccharides have one fucose-free N
acetyllactosaminyl unit and can be used as acceptors for recombinant alpha 1-3
fucosyltransferases in determining the biosynthesis pathways leading to
polyfucosylated selectin ligands.
PMID- 9648267
TI - Chemoenzymatic synthesis of a 3IV,6III-disulfated Lewis(x) pentasaccharide, a
candidate ligand for human L-selectin.
AB - The disulfated pentasaccharide 3-O-SO3(-)-beta-D-Galp-(1-->4)-[alpha-L-Fucp-(1-
>3)]-6-O-SO3(-)- beta-D-GlcpNAc-(1-->3)-beta-D-Galp-(1-->4)-D-Glcp was prepared
according to a chemoenzymatic approach, starting from 4-methoxybenzyl O-(4-O
acetyl-2,6-di-O-benzyl-beta- D-galactopyranosyl)-(1-->4)-O-2,3,6-tri-O-benzyl
beta-D-glucopyranoside, obtained in six steps from hepta-O-acetyl lactosyl
bromide. Coupling of this lactose derivative with O-(3,4,6-tri-O-acetyl-2-deoxy-2
phthalimido-beta-D-glucopyranosyl) trichloracetimidate afforded, after
dephthaloylation and re-N-acetylation, 4-methoxybenzyl O-(2-acetamido-2-deoxy
beta-D- glucopyranosyl)-(1-->3)-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1--
>4)- O-2,3,6-tri-O-benzyl-beta-D-glucopyranoside. Regioselective sulfation at the
primary position of the glucosamine residue was then successfully achieved and
the benzyl groups were removed. Enzymatic galactosylation of 4-methoxybenzyl O-(2
acetamido-2-deoxy-6-O-sulfo-beta-D- glucopyranosyl)-(1-->3)-O-beta-D
galactopyranosyl-(1-->4)-O-beta-D- glucopyranoside sodium salt, and subsequent
regioselective sulfation at position 3 of the outer galactose residue through the
stannylene procedure, led then to 4-methoxybenzyl O-(3-sulfo-beta-D-
galactopyranosyl)-(1-->4)-O-(2-acetamido-2-deoxy-6-sulfo-beta-D- glucopyranosyl)
(1-->3)-O-beta-D-galactopyranosyl)-(1-->4)-O-beta-D- glucopyranoside disodium
salt, which was finally fucosylated using human milk alpha-(1-->3/4)
fucosyltransferase affording, after anomeric deprotection, the target
pentasaccharide.
PMID- 9648268
TI - Fucosyltransferase-catalyzed formation of L-galactosylated Lewis structures.
AB - The Lewis (alpha 1-3/4) fucosyltransferase isolated from human milk could be used
for preparative fucosylations of the disaccharide acceptors Gal(beta 1
3)GlcNAc(beta 1-O)R (at position OH-4) and Gal(beta 1-4)GlcNAc(beta 1-O)R (at
position OH-3) [R = (CH2)8COOMe]. As donors GDP-L-Gal and deoxygenated
derivatives were used to lead to a series of novel modified trisaccharides of the
Lewis(a) and the Lewis(x) type, respectively.
PMID- 9648269
TI - beta-Glucosylation of chitooligomers by galactosyltransferase.
AB - Galactosyltransferase from bovine milk was found to be able to utilise UDP-Glc to
transfer Glc onto GlcNAc and chitooligomers[-beta-GlcNAc-(1-->4)-]n, n = 2-4.
beta-Glucosylated products were used in binding studies with NKR-P1A protein
cloned from rat natural killer cells.
PMID- 9648270
TI - Effect of organic cosolvents on the stability and activity of the beta-1,4
galactosyltransferase from bovine colostrum.
AB - The influence of various organic cosolvents on the stability and activity of the
beta-1,4-galactosyltransferase from bovine colostrum (GalT) and of its ancillary
enzyme UDP-galactose-4'-epimerase has been investigated using the glucosylated
alkaloid colchicoside (1) as a model substrate. It has been found that some
cosolvents, such as Me2SO and MeOH, can be used up to 20% v/v without any
influence on the performance of these enzymes, while others, such as
tetrahydrofuran, rapidly inactivated GalT at concentrations as low as 5% v/v.
These results have been exploited for the galactosylation of the poorly water
soluble coumarinic glucoside fraxin (2).
PMID- 9648271
TI - The chemoenzymatic synthesis of the core trisaccharide of N-linked
oligosaccharides using a recombinant beta-mannosyltransferase.
AB - The chemical synthesis of the beta-mannosyl linkage of N-glycans has presented a
great challenge to synthetic carbohydrate chemists. We have therefore
investigated the application of beta-mannosyltransferases to the preparative
synthesis N-linked core oligosaccharides. In this paper we report the
chemoenzymatic synthesis of beta-D-mannopyranosyl-(1-->4)-2-acetamido-2-deoxy
beta-D-glucopyranosyl- (1-->4)-2-acetamido-2-deoxy-alpha-D-glucopyranose on a
preparative scale using a phytanyl-linked acceptor in the presence of a
recombinant beta-(1-->4)-mannosyltransferase.
PMID- 9648272
TI - Structural characterization of the maltose acceptor-products synthesized by
Leuconostoc mesenteroides NRRL B-1299 dextransucrase.
AB - The glucooligosaccharides (GOS), produced by Leuconostoc mesenteroides NRRL B
1299 dextransucrase through an acceptor reaction with maltose and sucrose, were
purified by reverse phase chromatography. Logarithmic plots of retention time vs.
dp of the GOS gave three parallel lines suggesting the existence of at least
three families of homologous molecules. The structure (13C and 1H NMR
spectroscopy) and reactivity of the purified molecules of the three families were
investigated. All the products bear a maltose residue at the reducing end. The
GOS in the first family (named OD) contained additional glucosyl residues all
alpha-(1-->6) linked. The smallest molecule in this first series was panose or
alpha-D-glucopyranosyl-(1-->6)-D-maltose (dp 3). All the OD molecules were shown
to be good acceptors for dextransucrase in the presence of sucrose. The second
family, named R, was composed of linear GOS containing alpha-(1-->6)-linked
glucosyl residues and a terminal alpha-(1-->2)-linked residue at the non-reducing
end of the molecule; the smallest molecule in this family was alpha-D
glucopyranosyl-(1-->2)-D-panose (dp 4). The third family, R', was formed of GOS
containing additional residues linked through alpha-(1-->6) linkages that
constitute the linear chain, and an alpha-(1-->2)-branched residue located on the
penultimate element of the chain, near the non-reducing end. The smallest
molecule in this series is alpha-D-glucopyranosyl-(1-->6)-[alpha-D-glucopyranosyl
(1-->2)]-alpha-D- glucopyranosyl-(1-->6)-D-panose, dp 6. R and R' GOS are very
poor acceptors for L. mesenteroides NRRL B-1299 dextransucrase. This study makes
it possible to suggest a rather simple reaction scheme, where molecules Ri, R'i
and ODi of the same dp all result from the glucosylation of the same GOS: ODi-l.
PMID- 9648273
TI - Transfer reactions catalyzed by cyclodextrin glucosyltransferase using 4
thiomaltosyl and C-maltosyl fluorides as artificial donors.
AB - Cyclodextrin glycosyltransferase enzyme from Bacillus circulans catalyzed the
effective conversion of 4-thio-alpha-maltosyl fluoride into cyclo-alpha-(1-
>4(2))-thiomalto -tetraoside, -pentaoside, -hexaoside and linear
hemithiomaltooligosaccharides. However, under the same conditions, C-maltosyl
fluoride afforded only linear modified maltotetraose, maltohexaose and
maltooctaose in moderate yield.
PMID- 9648274
TI - Synthesis, cytotoxicity and antitumor activity of some new simplified pyrazole
analogs of the antitumor agent CC-1065. Effect of an hydrophobic group on
antitumor activity.
AB - Three simplified pyrazole analogs (7-9) of the antitumor agents CC-1065, were
synthesized. In in vitro assays, against L1210 cell lines all derivatives showed
a cytotoxicity in a pM range, values close to the natural target compound (+)-CC
1065. In in vivo tests, against disseminate L1210 leukemia cells, synthesized
compounds showed a good potency (O.D. 300 micrograms/Kg) but no activity. These
observations further validate the effect of the hydrophilic and/or hydrophobic
characteristics of the substituents present on the molecules, confirming the
relevance of this phenomena on in vivo activity. In fact in this case the
increase of hydrophobic characteristics of the molecules produce the loss of
activity, probably due to a worse bioavailability of the drugs in animals.
PMID- 9648275
TI - Synthesis, solvolytic stability and cytotoxicity of a modified derivative of
CPzI, a pyrazole analog of the alkylation subunit of the antitumor agent CC-1065:
effect of the nitrogen substitution on the functional reactivity.
AB - The synthesis and the comparative preliminary biological evaluation of a new
pyrazole analog (16) of the CC-1065 alkylating unit (CPI) are described. This new
derivative showed low cytotoxicity against L1210 murine leukemia (IC50 3064 nM)
with respect to reference compound, but contrarily to literature data, was found
to be more stable to solvolysis than the natural derivative (+/-)-N-Boc-CPI (pH
3, t1/2 = 212 h vs. 37 h). The results of such investigation showed that
alkylation of the pyrazole nitrogen caused a loss of cytotoxic activity in vitro
against tumor cells. This experimental observation allowed us to confirm the
importance of free N-H for the anticellular activity.
PMID- 9648276
TI - Mice's brain radioprotection: comparative efficacy of a series of aminothiols and
aminothiol precursors.
AB - A serie of radioprotective aminothiols was checked upon irradiation of the mice's
brain. Cysteamine protects efficiently the brain as soon as 15 minutes after its
administration. Among the tested aminothiols, it was the most effective compound.
2-isopropyl 1,3-thiazolane, rapidly hydrolysed, delivers a large amount of
cysteamine in the brain and was nearly as potent as exogenous cysteamine. The
other thiazolanes which delivered only progressively cysteamine or 2
mercaptopropylamine during a long period of time showed lesser efficacy. WR 2721
which did not penetrate the brain exhibited only a feeble radioprotection. The
imperviousness to straight active aminothiols may be compensated by the diffusion
of their precursors across the blood brain barrier and by their speed of
hydrolysis, yielding active aminothiols during a short period of time between
their administration and the irradiation.
PMID- 9648277
TI - Mice's rectum radioprotection: comparative efficacy of a series of aminothiols
and aminothiol precursors.
AB - In mice, in a test of rectal gamma irradiation, cysteamine and cysteine are poor
radioprotectors relative to thiazolanes or WR 2721. Among the tested prodrugs, 2
isopropyl 1,3-thiazolane was nearly as efficient as WR 2721 as soon as 15 minutes
after its administration. The guarantee of radioprotection is the effective
presence of the active aminothiols in the intracellular room during the
irradiation. In this study, enterocytes of the rectal mucous membrane were not
sufficiently permeable to exogenous cysteine or cysteamine. The cell
imperviousness to these straight active aminothiols was compensated by the
diffusion of their precursors across the membrane.
PMID- 9648278
TI - Synthesis of some indane derivatives of central muscle relaxant and
anticonvulsant profiles.
AB - A series of 2,2-bis(hydroxymethyl)indane derivatives 1a-f, 2a-e and 3a-f were
synthesized to investigate their central muscle relaxant and anticonvulsant
activities. The synthesized compounds 1a-f, 2a-e and 3a-f were found to be devoid
of central muscle relaxant activity using meprobamate (100 mg/kg) as a reference
standard. However, they showed remarkable anticonvulsant properties in a dose of
80 mg/kg (s.c.) compared with diphenylhydantoin sodium (80 mg/kg) as a reference
standard.
PMID- 9648279
TI - Some 1-substituted 3-aryl-1,4-dihydro-1,2,4-triazino[4,3-a]-benzimidazoles and
their vasodilatory activities.
AB - In this study, some 1-substituted 3-aryl-1,4-dihydro-1,2,4-triazino[4,3
a]benzimidazole derivatives were synthesized, their structures were elucidated,
and their vasodilatory activities were examined. It was found that the compounds
under investigation showed appreciable vasodilatory activity.
PMID- 9648280
TI - N-(2-pyridinyl)-2-[2(3H)-benzazolone-3-yl]acetamides: synthesis, antinociceptive
and anti-inflammatory activity.
AB - Eighteen N-(2-Pyridyl)-2-[2(3H)-benzazolone-3-yl]acetamide derivatives have been
synthesized. The chemical structure of the compounds have been elucidated by
elemental analysis, IR and 1H NMR spectral data and their antinociceptive and
anti-inflammatory activities were tested in mice. Compound VII o has shown the
highest antinociceptive activity, and VII g, j, k, r exhibited relatively high
antinociceptive activity. In addition, compounds VII d, f, j, p showed
statistically significant anti-inflammatory activity.
PMID- 9648281
TI - The newly synthetized pyridobenzoxazocynone inhibits HIV-1 reverse transcriptase
activity.
AB - We synthetized pyridobenzoxazocynone that differs in the enlarged eight-membered
heterocyclic system from the basic structure of pyridobenzoxazepinones a known
class of non-nucleoside HIV-1 reverse transcriptase inhibitors.
Pyridobenzoxazocynone hydrochloride was found to inhibit HIV-1 reverse
transcriptase activity. At concentration 0.35 microM the enzyme activity
decreased by 64 +/- 14%. Higher concentrations of pyridobenzoxazocynone
hydrochloride completely abolished the enzyme activity expressed as radioactivity
of acid insoluble products. These results suggest that pyridobenzoxazocynones may
represent a new class of HIV-1 reverse transcriptase inhibitors.
PMID- 9648282
TI - Synergistic effect of microwave heating and hydrogen peroxide on inactivation of
microorganisms.
AB - Escherichia coli K-12 isogenous strains and Pseudomonas aeruginosa 102 were used
to study the synergistic effects of combined microwave heating at short-time
processing with low concentrations of hydrogen peroxide. The effect of microwave
heating to temperatures of 40, 50 and 60 degrees C, as well as the concentration
of hydrogen peroxide (0.05, 0.08 and 0.1%), the sequence of the agents' use, the
nature of microorganisms on the survival of cells, DNA damages and interaction
factors were studied. A method of anomalous viscosity time dependencies (AVTD)
was used for measurement of the changes of genome conformational state (GCS)
simultaneously with bacterial survival determination. The synergistic effect of
microwave heating and low concentrations of hydrogen peroxide was observed under
combined application, and reached a maximum when the cells were exposed to
microwave heating to 50 degrees C and 0.08% hydrogen peroxide simultaneously.
Both maxima of cell destruction and DNA injuries have been achieved by successive
exposure to (MW + 10 min H2O2) to 60 degrees C and 0.08% hydrogen peroxide. The
mechanisms of synergistic effects, the role of a disturbance of DNA repair and
the interaction of sublethal injuries caused by different agents are discussed.
PMID- 9648283
TI - Structure determines function of the retina, a neural center. 2. The second,
third and fourth circuits.
AB - Three retinal circuits are analyzed on the bases of established circuit diagrams.
The synaptic interaction at one circuit involves depolarizing bipolar cells
connected to rods and shows the important contribution to function of the
connections between cones and rods including connections of cones to bipolar
cells connected to rods. Another circuit explains that one type of bipolar cell
is depolarized at cessation of the stimulus. Because each photoreceptor is
connected to both on- and off- bipolar cells, on- and off- responses are
generated from each photoreceptor. The cone connections to rods and to bipolar
cells connected to rods extend rod vision to low ambient illumination while the
absence of corresponding connections at cone terminals leads to cone vision being
blocked at low ambient illumination. The cone connections raise the threshold for
stimulation of bipolar cells connected to rods and lower temporal resolution of
rod vision relative to cone vision. The timing of interaction between bipolar
cells, amacrine cells and ganglion cells in the inner plexiform layer makes
inhibitory and facilitatory modulation of ganglion cell potential establish
optimal conditions for ganglion cell activation. The agreement between bipolar
cell responses determined on the basis of the analysis of the circuit diagrams
and the responses recorded from bipolar cells shows that the function of a neural
center such as the retina can be analyzed on the basis of circuit diagrams.
PMID- 9648284
TI - Cytomegalovirus infection in the submandibular and parotid salivary glands of an
African grass mouse (Arvicanthus dembeensis).
AB - The submandibular and parotid glands of one of five specimens of African grass
mice (Arvicanthus dembeensis) were found to be infected with cytomegaloviruses,
producing a profound cytomegaly in certain cells at the juncture of secretory
endpieces and intercalated ducts. These cytomegalic cells tended to have multiple
nuclei, many of which contained a characteristic reticular inclusion. The viruses
appeared to arise in association with the intranuclear inclusions, then passed
through the nuclear envelope to the cytoplasm where they budded into Golgi
saccules or into small vacuoles, presumably of Golgi origin. Fusion of small
virus-carrying vacuoles led to the formation of large vacuoles containing a
plethora of viruses. Viruses were liberated into gland lumina via fusion of the
vacuoles with the luminal plasmalemma. Fusion of vacuoles with dehiscent ones
resulted in a form of chain exocytosis. The development of cytomegaloviruses in
salivary glands may differ in details in a species-specific manner.
PMID- 9648285
TI - Characterisation of breast stromal fibroblasts: cell surface distribution of
collagen type IV, laminin and fibronectin.
AB - A number of cells--fibroblasts, chondrocytes and osteoblasts for example--lack
the conspicuous cell surface specialisation known as lamina: instead, they
possess subplasmalemmal linear densities (SLDs). These have been documented
ultrastructurally as having a lamina-like external component but the extent to
which they resemble true lamina in terms of protein composition has not been
investigated. The relationship of the external component of the SLD to true
lamina was examined in this study by light microscope immunostaining,
conventional transmission electron microscopy and immuno-electronmicroscopy in
intralobular stromal fibroblasts. These were studied in normal peri-tumoral
breast tissue in 17 patients undergoing surgery for breast lesions. For
ultrastructural immunostaining the indirect immunoperoxidase procedure was used
on cryostat sections followed by embedding in epoxy resin. To varying degrees,
collagen type IV, laminin and fibronectin antibodies stained fibroblasts and
macrophages at the light microscope level. Using immuno-electronmicroscopy, all
three antibodies localised as foci on fibroblast and macrophage surfaces. These
occurred with a frequency comparable to that of SLDs as seen in non
immunostaining ultrathin sections. These observations represent a first attempt
to define the protein composition of SLDs in fibroblasts in vivo. They provide an
opportunity of comparing these structures with true lamina and form a basis for
understanding how fibroblasts interact with their environment.
PMID- 9648286
TI - Expression of laminin 1 and 2 in brain tumor vessels. An immunohistochemical
study.
AB - Components of the blood-brain barrier (BBB) include capillary endothelial cells,
the vessel basement membrane (BM) and glial cell interface. While endothelial
cell peculiarities are well known and thoroughly studied, BM morphology and
functional properties are not. Vessel BM throughout the body is composed of
laminin 1, the most common variant of laminin, which is made up of alpha 1, beta
1, and gamma 1 laminin chains, while cerebral vessel BM has been reported to also
express the alpha 2 chain. In the present study, we show that the BM of newly
formed vessels in brain tumors presents the same immunohistochemical structure as
normal brain vessel BM, expressing alpha 1, alpha 2, beta 1, and gamma 1 laminin
chains. The function of this particular vessel structure in the central nervous
system is not yet completely understood; however, we hypothesize that vessel BM
could play a role in impeding the extraneural spreading of brain tumors.
PMID- 9648287
TI - Angio-tumoral laminin in murine tumors derived from human melanoma cell lines.
Immunohistochemical and ultrastructural observations.
AB - Cells in tissues interact with each other and with the extracellular matrix as
part of a structural and informational unit. During cancer progression, tumor
cells participate in the formation of a neotissue involving other cells and
matrix. We recently observed in melanoma an association between tumor and
endothelial cells via an amorphous matrix containing free laminin. The pericytic
location of melanoma cells in this angio-tumoral complex raised the question of
an intramesenchymal migration of metastatic melanoma cells promoted by free
laminin along the endothelium. However the respective roles of melanoma cells and
endothelial cells in laminin secretion were not clear. In an attempt to clarify
the latter issue, we injected into mice three human melanoma cells lines, one
secreting laminin and two that did not, in order to identify the source of
laminin secretion in the subsequent interactions between tumor cells and vascular
endothelium. Using immunohistochemistry and electron microscopy we observed in
all three cases an amorphous matrix containing laminin between tumor and
endothelial cells. The fact that two cell lines did not secrete laminin suggests
that the periendothelial/peritumoral laminin could be of endothelial origin.
Given the presence of laminin alone during intramesenchymal angiogenesis and
embryogenesis, we propose an analogous role for endothelial laminin in
facilitating the migration of melanoma cells along the abluminal surface of the
endothelium.
PMID- 9648288
TI - Bone remodeling and macrophage differentiation in osteopetrosis (op) mutant mice
defective in the production of macrophage colony-stimulating factor.
AB - Mice homozygous for the osteopetrosis (op) mutation are characterized by
defective differentiation of osteoclasts, monocytes, and tissue macrophages due
to a lack of functional macrophage colony-stimulating factor (M-CSF/CSF-1)
activity. In young (4-6 week-old) op/op mice, the bone marrow cavities were
filled with spongious bone. In aged (50-72 week-old) op/op mice, the bone marrow
cavities were markedly reconstructed and marrow hematopoiesis was expanded.
Numbers of osteoclasts and bone marrow macrophages in aged op/op mice were
increased but most of the osteoclasts were mononuclear cells and showed poorly
developed ruffled borders. Lysosomes of bone marrow macrophages were laden with
abundant crystalloid materials in aged op/op mice and aged littermate mice.
However, such macrophages were not observed in young op/op mice nor in young
littermates. In contrast to the marked increase in numbers of osteoclasts and
macrophages in the bone marrow, the number of Kupffer cells in the liver did not
increase in aged op/op mice. Kupffer cells in aged op/op mice did not show
ultrastructural maturation with aging and contained a few crystalloid structures.
M-CSF administration to aged op/op mice induced numerical increases in Kupffer
cells and lysosomes in Kupffer cells, disappearance of crystalloid structures in
lysosomes of Kupffer cells, and the development of ruffled border in osteoclasts.
These findings indicate that M-CSF-independent mechanisms for macrophage and
osteoclast development in aged op/op mice are restricted to bone marrow. M-CSF
plays important roles in the differentiation of macrophage and osteoclast and the
production and function of lysosomes.
PMID- 9648289
TI - Quantitative comparison of the morphology of the microvasculature of primary lung
lesions and metastatic brain tumours.
AB - Endothelial cells that make up microvessels display a differential expression of
structure and function that allows them to meet the requirements of the tissues
they vascularize. The growth of tumours requires neovascularization that occurs
by angiogenesis, a process by which new capillaries are formed from existing
vessels. It has been proposed that the local environment determines the
morphological characteristics of the vessels that vascularize it. The present
study is a quantitative investigation of the properties of capillaries that may
contribute to their permeability and their general morphology. Tissue samples
were taken from primary non-small cell lung carcinomas and from the same tumour
type that had metastasized to brain. Normal samples were taken from tissue
distant from the site of pathology. Using transmission electron microscopy,
profiles of capillaries from the tissue samples were examined and photographed.
Image-analysis was performed to measure vesicular and mitochondrial density,
vessel size and vessel wall thickness. The results showed that the morphology of
the capillaries that vascularize the primary lung tumours differs from the
morphology of the capillaries that vascularize the metastases of these tumours in
the brain. In addition to differences in the quantitative observations,
qualitative differences were observed with respect to the presence of
fenestrations in the vessel wall, found only in brain tumour vessels, and the
presence of 'open' junctions, seen only in lung tumour vessels. These results
suggest that although the environment of the tumour changed the morphology of the
vessels so they were no longer normal, it did not have the same effect on the
vessels that vascularize it at the two different sites. Therefore, the response
of microvessels in the host tissue to factor(s) produced by tumour cells may be
multifaceted and dependent upon the properties of local vessels.
PMID- 9648290
TI - Further studies on the phagocytic capacity of chicken thrombocytes.
AB - Thrombocytes, functional analog to mammalian platelets, have been described as
the primary circulating phagocyte in chicken blood when challenged with bacteria
(Chang and Hamilton, 1979). In order to determine if the phagocytic capacity
could be extended to protozoa, interaction of chicken thrombocytes with
tachyzoites of Toxoplasma gondii and bloodstream trypomastigotes of Trypanosoma
cruzi was performed. Interaction with Staphylococcus aureus and Escherichia coli
was also performed using fluoresceinated and living bacteria, to be examined by
fluorescence microscopy (after ethidium bromide staining) and transmission
electron microscopy (after ruthenium red fixation). Using these approaches it was
possible to distinguish internalized from attached bacteria. T. cruzi was only
found attached to the thrombocyte surface while T. gondii could be observed
within the cell. To determine if T. gondii invasion was active or by
phagocytosis, interaction was performed under conditions where active penetration
and phagocytosis were inhibited by previous fixation of the parasites or
treatment of thrombocytes with cytochalasin D, respectively. Interactions with
fixed T. gondii showed only attached parasites. Cytochalasin D treated
thrombocytes could still be found with internalized T. gondii. By fluorescence
and transmission electron microscopy it was possible to observe a small number of
bacteria internalized by thrombocytes. These findings show that T. gondii invade
thrombocytes through an active penetration process and these blood cells cannot
be considered as the primary circulating phagocyte in chicken.
PMID- 9648291
TI - Investigation of morphological changes in absorptive cells in young adult and
infant mice fed different amounts of iron for a long-term.
AB - The changes in fine structure of the intestinal tract in young adult (4 week-old)
and infant (2 week-old) mice fed a diet containing different amounts of iron salt
(Fe-0, Fe-2.5, Fe-25: 0, 2.5 and 25 mg Fe/100 g diet, respectively) for a long
term (1 or 2 weeks) were investigated. The hepatic iron levels in infant mice fed
Fe-25 for 2 weeks were significantly higher than those observed after 1 week of
feeding, but there was no such increase in young adult mice during the feeding
period. Observations of fine structure indicated typical signs of impairment of
enterocytes due to excess iron such as the opening of intercellular junctions
between adjacent epithelial cells and the marked appearance of eosinophilic
leukocytes outside the basement membrane in young adult and infant mice fed Fe
25. The frequency of the opening in intercellular junctions increased in young
adult mice fed Fe-25 for 2 weeks, but decreased in infant mice. On the contrary,
under iron-deficient conditions, the frequency in infant mice was higher than
that in young adult mice. The appearance of eosinophilic leukocytes indicated
that some immunological reaction was elicited in both groups of mice fed Fe-25
for 2 weeks.
PMID- 9648292
TI - Ultrastructural changes in rat cornea after prolonged hypobaric hypoxia.
AB - A study was performed to evaluate the effect of prolonged environmental hypobaric
hypoxia on the ultrastructure of rat cornea. 60-day-old female Wistar rats were
exposed to a simulated altitude of 5,500 m (350 mmHg) and pO2 of 76 mmHg for 30
days. Control rats were exposed to atmospheric sea level pressure (760 mmHg) and
pO2 of 150 mmHg, for the same period. Ultrastructural analysis of the corneal
epithelium did not reveal any relevant difference between control and treated
rats. In contrast, the corneal stroma of rats subjected to hypoxia showed
vascularization with advanced vessel differentiation and signs of active
proliferation. The endothelium of hypoxic cornea showed swollen mitochondria and
large empty cytoplasmic areas. The endothelial intercellular junctions could
hardly be identified in the hypoxic condition. Nevertheless, the most evident
change in hypoxic cornea was in Descemet's membrane, which was considerably
thickened, to approximately twice that of the control specimen. These results
suggest that environmental hypobaric hypoxia induces marked alterations in the
corneal stroma and endothelium morphology, probably related to reduced oxygen
tension in the aqueous humor, consequent to hypoxemia.
PMID- 9648293
TI - Birbeck granules: contribution to the comprehension of intracytoplasmic
evolution.
AB - We investigated the ultrastructure of Birbeck granules which are found in some
malignant histiocytoses such as histiocytosis X, Letterer-Siwe disease, Hand
Schuller-Christian disease, eosinophilic granuloma of the bone and self-healing
reticulohistiocytosis. The research is based on the systemic study of Birbeck
granules, from their formation to intracytoplasmic development, examining with
the electron microscope at regular intervals ultrathin sections derived from
biopsies of two cases of Langerhans cell histiocytosis.
PMID- 9648294
TI - Liver ultrastructural pathology in mice infected with Plasmodium berghei.
AB - As liver can be an important target organ in malaria, we performed an
ultrastructural study of hepatic alterations in the final stage of Plasmodium
berghei infection in mice. Significant hepatocyte abnormalities were found. An
elevated number of cells showed mitochondria with a high electron-dense matrix
and multiple changes in shape and size, alterations in the structure of Golgi
complex, swelling and disorganisation of both rough and smooth-surfaced
endoplasmic reticulum, differently shaped peroxisome nucleoids, and disappearance
of glycogen granules. In other areas the hepatocytes were significantly altered
with diminished microvilli and exhibited myelin-like figures, autophagic
vacuoles, abundant lipid droplets, and swollen mitochondria in their cytoplasm.
Necrotic and atrophied hepatocytes with scarce microvilli in the Disse space and
biliary canaliculi could be seen. Parasitised red blood cells and parasite debris
were found inside degenerated hepatocytes. Alterations were also noticed in
microvasculature, including thickened endothelial cells with swollen
mitochondria, lysosomes and autophagic vacuoles in their cytoplasm. Our results
demonstrate that hepatocyte damage is an important finding associated with the
advanced stages of P. berghei malarial infection, which may lead to liver
dysfunction in this disease.
PMID- 9648295
TI - Evolutionary sperm morphology and morphometry in armadillos.
AB - Little is known about the evolution of vertebrate spermatozoa. In most eutherian
taxa a high degree of uniformity in sperm shapes and dimensions among species was
observed. The aim of this work is to trace a possible evolutionary change in
sperm morphology and morphometry in dasypodids. The main difference between the
spermatozoa of the studied armadillos is the shape of the sperm heads. We have
classified the spermatozoa into 4 different groups according with their head
shapes. Sperm from group 1 (Dasypus) are considered ancestral and are clearly
separated from the others. The remaining sperm types are derivative ones; those
from group 2 (Tolypeutes) are farther from those of groups 3 (Priodontes and
Cabassous) and 4 (Chaetopractus, Zaedyus and Euphractus) which would have
recently differentiated from each other. The sperm shape and size are not
constant across taxa in armadillos; an important evolutive differentiation was
established on the sperm morphology and morphometry between the different genera
in Dasypodidae.
PMID- 9648296
TI - Pagetic osteoclasts formed in vitro: absence of paracrystalline inclusions.
AB - In Paget's disease of bone, osteoclasts are increased in number and size and
contain intracellular paramyxoviral-like inclusions which cross-react with
antibody against measles, respiratory syncytial, and canine distemper viral
nucleocapsid antigens. Moreover, measles virus nucleocapsid transcripts are
present in pagetic osteoclasts and their mononuclear precursors formed in vitro.
The present study was undertaken to morphologically assess pagetic osteoclasts
formed in culture; special attention has been directed towards the
ultrastructural identification of nuclear and cytoplasmic inclusions. Pagetic
osteoclasts were produced in long-term cultures of non-adherent bone marrow
mononuclear cells derived from involved bone of patients with Paget's disease.
These cultured osteoclasts had many of the ultrastructural features of pagetic
osteoclasts in vivo. Of interest, no viral-like inclusions were observed in
either the multinucleated osteoclasts or mononuclear cell precursors in these
cultures. These data suggest that other factors in the bone microenvironment are
required for viral nucleocapsid formation in pagetic osteoclasts.
PMID- 9648297
TI - Fighting germs.
PMID- 9648298
TI - The split brain revisited.
PMID- 9648299
TI - HIV 1998: the global picture.
PMID- 9648300
TI - Improving HIV therapy.
PMID- 9648301
TI - How drug resistance arises.
PMID- 9648302
TI - Viral-load tests provide valuable answers.
PMID- 9648303
TI - When children harbor HIV.
PMID- 9648304
TI - Preventing HIV infection.
PMID- 9648305
TI - HIV vaccines: prospects and challenges.
PMID- 9648307
TI - Coping with HIV's ethical dilemmas.
PMID- 9648306
TI - Avoiding infection after HIV exposure.
PMID- 9648308
TI - GPs and methadone. Primum non nocere.
PMID- 9648309
TI - Plagiocephaly--what is the cause?
PMID- 9648310
TI - Atlas rotation following a blow on the neck.
PMID- 9648311
TI - Where have the generalists gone?
PMID- 9648313
TI - Gastroesophageal reflux in adults. Where are we now?
AB - BACKGROUND: Gastroesophageal reflux is a common form of dyspepsia affecting 20
40% of the population. OBJECTIVE: Adults experiencing gastroesophageal reflux
represent a challenging subgroup of patients presenting to primary care
physicians. Identification of those patients who require medical therapy and
ultimately surgery, requires an understanding of the mechanisms of disease, the
available diagnostic tools as well as the array of acid suppressive agents
currently in use. DISCUSSION: Successful therapy of gastroesophageal reflux may
reduce complicated oesophageal and extraoesophageal disease.
PMID- 9648312
TI - Gastroesophageal reflux in children.
AB - BACKGROUND: Gastroesophageal reflux is common in small children. It is important
to recognise that its natural history and management differ from reflux in
adults. OBJECTIVE: This article will summarise the clinical presentation,
pathophysiology, appropriate investigations and therapy of reflux in small
children. DISCUSSION: A small amount of regurgitation is common in infancy, and
is only pathological if it results in harm. In children, reflux-induced injury
can result from either acid exposure, nutrient loss or respiratory complications.
Recognised presentations include heartburn, oesophagitis, infant irritability,
dysphagia, haematemesis, stricture, growth failure, aspiration, apnoea and
pneumonia. Excessive crying and irritable behaviour in infancy can be due to a
variety of causes, but there is a fashionable tendency to assume that
gastroesophageal reflux is a major factor. Regurgitation can be a symptom of
other conditions such as infection or metabolic disturbance. It is important to
carefully evaluate any infant with distressed behaviour to exclude a significant
medical cause. Prolonged oesophageal pH monitoring is a very useful means of
linking episodes of reflux with putative symptoms. The severity of
gastroesophageal reflux tends to improve with age in infants and this should be
considered when advising appropriate therapy, especially fundoplication.
PMID- 9648314
TI - Classifying hiatus hernia. Does it make a difference to management?
AB - BACKGROUND: Hiatus hernia is a not uncommon finding but often does not require
treatment unless symptomatic. At present, hernias are categorised into either the
sliding variety or the rolling type. Understanding how these differ as to their
symptoms and their cause provides a basis for a logical treatment plan.
OBJECTIVE: To describe the differences between a sliding and a rolling hernia,
highlighting the management approaches for each. DISCUSSION: Sliding hernia is
often associated with reflux and usually treated medically, but surgery is needed
for some patients. Para-oesophageal hernia may be a serious problem with major
complications. Large or symptomatic para-oesophageal hernias need surgical
treatment.
PMID- 9648315
TI - Acid pump inhibitors. The treatment of gastroesophageal reflux.
AB - BACKGROUND: The place of acid pump inhibitors at the top of the efficacy table in
the league of reflux therapies, and their eager patient acceptance, has aroused
debate on their role. OBJECTIVE: To understand the role of gastric acid and its
inhibition in the pathogenesis and treatment of gastroesophageal reflux disease.
DISCUSSION: Gastroesophageal reflux disease results from excessive exposure of
the oesophagus to acidic contents. Acid pump inhibitors provide the most
effective medical control of gastric acid throughout day and night, returning
oesophageal pH to normal levels. They provide fast symptom relief and rapidly
restore quality of life in all reflux patients more effectively than H2 receptor
antagonists or prokinetic drugs. APIs heal oesophagitis of all grades of severity
and provide safe, effective maintenance of healing with prevention of
complications in longer term use.
PMID- 9648316
TI - Meningococcal disease. Is early diagnosis possible?
AB - Meningococcal disease is a public health problem because of its high mortality
and is one disease that many GPs have not seen. Case reports illustrate that
presentation is rarely classic 'meningitis' and further research is required to
enable earlier detection.
PMID- 9648317
TI - Questionnaire design and surveys.
AB - Surveys provide powerful means for systematic collection of information to test
hypotheses and quantify the extent and nature of phenomena. This article
discusses survey types and questionnaire design, and outlines 10 steps for
planning a survey.
PMID- 9648318
TI - Low back pain in mineral sand mine workers. Incidence and management.
AB - OBJECTIVES: To establish the prevalence of low back pain suffered by workers in
three mineral sand mining companies operating in the south west of Western
Australia; to determine what use was made of health care providers by those
experiencing low back pain; to derive the perceptions of the value of the
treatment for low back pain by health care providers. METHOD: A total of 350
questionnaires were distributed to sand mine workers who were asked to complete
the questionnaires which were collected 1 week later. RESULTS: completed
questionnaires were returned by 204 workers giving a 58% response rate. Seventy
seven percent of male workers and 60% of female workers could remember suffering
low back pain sometime in their lives. Low back pain was experienced by 61% of
male sufferers and 57% of female sufferers at least two to three times a month. A
total of 16% of men and 12% of women experienced low back pain on a daily basis
while 30% of men and 22% of women reported that the type of work they were doing
increased their low back pain. Only 19% of all male workers and 6% of all female
workers had ever taken time off work due to low back pain with the average time
taken off work for an acute episode, being 14 days. Overall, 47% of respondents
indicated that the treatment received from general practitioners was ineffective,
and only 16% of respondents assessed GPs as being better than average.
Chiropractors were rated higher than physiotherapists or general practitioners in
providing the most effective treatment for low back pain. Mobilising exercises
were considered to be better treatment than analgesics or anti-inflammatory
medication. CONCLUSION: Low back pain is a common problem among mineral sand mine
workers who preferred the services of the chiropractor or the physiotherapist to
the general practitioner. Physical treatment modalities with stretching and
mobilising exercises were preferred to pharmacological treatment.
PMID- 9648319
TI - Pressure induced pseudodermatitis.
PMID- 9648320
TI - What has the patient been taking?
PMID- 9648321
TI - Ankle roll. An approach to assessment.
PMID- 9648322
TI - Acute fever and skin rash in a young woman.
PMID- 9648323
TI - Practice tip. Instilling eye drops in children.
PMID- 9648324
TI - What is folliculitis?
PMID- 9648325
TI - Selective attention to real phobic and safety stimuli.
AB - Many previous information processing studies have noted that people with severe
anxiety selectively attend to threat stimuli. The experiment reported here tests
the hypothesis that, when real threat stimuli are used instead of semantic
stimuli, attention may be divided between threat and safety. Spider phobics and
controls participated in a reaction time experiment, in which the target stimulus
(a light) was programmed to randomly occur either by the only door to the room or
by the wall opposite that door. They were asked to press a response button as
soon as they detected the light coming on by the wall or by the door. Next, for
half the participants, a live Zebra Tarantula was placed next to the stimulus
light, either by the door (threat and safety/escape coincide) or by the wall
(threat and safety/escape divided), and the experiment repeated. The rest of the
participants repeated the baseline condition to control for practice effects.
Response latencies to the light stimuli were analysed. Results suggest that
spider phobics (but not controls) were faster to respond to the light when it
occurred in the location where the threat and the escape stimuli coincided, (when
the spider was by the door), than when it occurred in the location where the
threat and the escape stimuli were divided (when the spider was by the wall).
These results suggest that phobics may allocate attention not only to threat but
also to safety. It is proposed that such effects may be less detectable, or
absent, when the threat stimuli are semantic or symbolic because participants
discriminate between threat and its symbolic representation.
PMID- 9648326
TI - The impact of personality disorders on treatment outcome of anxiety disorders:
best-evidence synthesis.
AB - Thirty-five studies were traced addressing the impact of comorbid personality
disorders on treatment outcome of anxiety disorders. The conclusions of this
review are based on the best-evidence procedure. We used two selection criteria
that studies had to meet to be included in the present review. The study design
had to be prospective and a (semi)structured interview had to be used for the
assessment of personality disorders. From the fifteen selected studies it cannot
be concluded that, in general, personality disorders affect treatment outcome for
anxiety disorders negatively. We can only suspect that some personality disorders
may have an adverse impact upon treatment outcome in anxiety disorders, and they
should be investigated further. For the time being, in clinical practice one has
to be cautious in relating personality disorders to less well treatment outcome
in axis I anxiety disorders.
PMID- 9648327
TI - A retrospective study of the learning history origins of anxiety sensitivity.
AB - Anxiety sensitivity (AS; the fear of anxiety-related sensations) has been
proposed as a risk factor for the development of panic disorder. The present
study involved a conceptual replication of Ehlers' (1993, Behaviour Research and
Therapy, 31, 269-278) study on childhood learning experiences and panic attacks,
but also extended her work by investigating the relationship between early
learning experiences and the development of AS, in a non-clinical sample. A
sample of 551 university students participated in a retrospective assessment of
their childhood and adolescent instrumental and vicarious learning experiences
with respect to somatic symptoms (i.e. anxiety and cold symptoms, respectively)
using an expanded version of Ehler's (1993) Learning History Questionnaire. AS
levels were assessed using the Anxiety Sensitivity Index, and panic history was
obtained using the Panic Attack Questionnaire, Revised. Contrary to hypotheses,
the learning experiences of high AS individuals were not found to be specific to
anxiety symptoms, but involved parental reinforcement of sick-role behavior
related to somatic symptoms in general. High AS subjects reported both more
anxiety and cold symptoms prior to age 18 than individuals with lower levels of
AS. In addition, both cold and anxiety symptoms elicited more special attention
and/or instructions from parents for high AS individuals to take special care of
themselves. These findings are contrasted with the results for self-reported
panickers who reported more learning experiences (modeling and parental
reinforcement) specific to anxiety-related symptoms, than the non-panickers. The
results suggest that higher-than-normal levels of AS may arise from learning to
catastrophize about the occurrence of bodily symptoms in general, rather than
anxiety-related symptoms in particular.
PMID- 9648328
TI - Private body consciousness, anxiety and pain symptom reports of chronic pain
patients.
AB - An information processing model of pain symptom perception and reporting predicts
that individuals prone to high levels of attentional self-focus and negative
affect will report more pain than individuals low in these characteristics. Past
research on college student and medical patient samples has shown that
individuals high in private body consciousness (PBC), or attentional self-focus
and who report higher levels of anxiety report more pain symptoms than
counterparts low in PBC and anxiety. The present study examined effects of PBC
and anxiety on pain reports of individuals suffering chronic pain (N = 144). Pain
patients suffering chronic headache, low back pain, rheumatoid arthritis and
fibromyalgia were included in the sample. A non-pain control sample (N = 31) was
also studied to examine potential differences between controls and pain patients.
Results indicated that pain patients reporting high levels of PBC reported more
pain, although the effects of anxiety on pain reports among pain patients was not
significant. Controls did not differ from pain patients on PBC, nor did the 4
groups of pain patients differ on PBC, suggesting PBC is a dispositional
variable. Implications for the importance of attentional self-focus in pain
symptom reporting are discussed.
PMID- 9648329
TI - Evidence for a non-associative model of the acquisition of a fear of heights.
AB - Theories that fear results from previous traumatic experience (i.e. conditioning
theories) have enjoyed widespread support for over half a century. Recent
research, however, has cast doubt on the validity of these models in some
specific phobias. Two studies on the etiology of height phobia have obtained
findings consistent with a non-associative, evolutionary explanation of fear
acquisition (Menzies and Clarke, 1993a, Behaviour Research and Therapy, 31, 355
365; Menzies and Clarke, 1995a, Behaviour Research and Therapy, 33, 795-805).
Unfortunately, the retrospective nature of these studies limits the conclusions
that can be drawn from these data. Like all retrospective research, these studies
depend on adult subjects imperfect ability to recall conditioning events that may
have occurred many years earlier. The present investigation overcomes these
methodological shortcomings by examining the relationship between putative
conditioning events before the age of 9 yr and the presence of height fear at
ages 11 and 18 yr in a large birth cohort studied longitudinally. To our
knowledge this is the first study that has prospectively examined the
relationship between relevant traumatic events early in life and the onset of
height fear in late adolescence. No positive relationship was found between a
history of falls resulting in injury (i.e. fracture, dislocation, intracranial
injury or laceration) before the age of 9 and fear of heights at age 11 or 18.
Interestingly, falls resulting in injury between the ages of 5 and 9 occurred
more frequently in those without a fear of heights at 18 (P < 0.01)--a finding in
the opposite direction to that predicted by conditioning theory but consistent
with non-associative theories of fear acquisition. In general, the results
provide strong support for non-associative models of fear and are difficult to
reconcile with conditioning theories.
PMID- 9648330
TI - A measure of anxiety symptoms among children.
AB - The Spence Children's Anxiety Scale (SCAS) is a child self-report measure
designed to evaluate symptoms relating to separation anxiety, social phobia,
obsessive-compulsive disorder, panic-agoraphobia, generalized anxiety and fears
of physical injury. The results of confirmatory and exploratory factor analyses
supported six factors consistent with the hypothesized diagnostic categories.
There was support also for a model in which the 1st-order factors loaded
significantly on a single 2nd-order factor of anxiety in general. The internal
consistency of the total score and subscales was high and 6 month test-retest
reliability was acceptable. The SCAS correlated strongly with a frequently used
child self-report measure of anxiety. Comparisons between clinically anxious and
control children showed significant differences in total SCAS scores, with
subscale scores reflecting the type of presenting anxiety disorder of the
clinical samples.
PMID- 9648331
TI - Thought suppression produces a rebound effect with analogue post-traumatic
intrusions.
AB - Attempts to suppress traumatic material may be involved in the development and
maintenance of post-traumatic stress disorder (PTSD). In order to investigate
this possibility, analogue post-traumatic intrusions were induced in normal
participants by means of a distressing film. For comparison, a second film was
used to induce intrusions about polar bears. It was hypothesized that the
suppression of these intrusions would produce an immediate decrease but a delayed
increase ("rebound effect") in their frequency. It was also predicted that the
rebound effect would be larger for the analogue traumatic intrusions. Each film
was followed by two consecutive time periods during which participants' thoughts
were recorded. During the first period, the suppression group was instructed to
suppress thoughts about the film whilst the control group merely recorded their
thoughts. During the second period, both groups merely recorded their thoughts.
The results supported the immediate decrease hypothesis for both types of
intrusion. As predicted, there was a rebound effect for analogue traumatic
intrusions although not for polar bear thoughts. Several methodological issues
relating to the findings are highlighted. The possible implications of a rebound
effect with trauma-relevant intrusions are discussed with reference to PTSD.
PMID- 9648332
TI - The effect of attempted thought suppression in acute stress disorder.
AB - Attempted suppression of traumatic memories was investigated in survivors of
motor vehicle accidents with acute stress disorder (ASD; n = 24) and without ASD
(n = 24). Participants monitored their trauma-related thoughts for three 5-minute
periods. In Period 1, participants were instructed to think about anything. For
Period 2, participants were administered suppression or non-suppression
instructions relating to thoughts of the trauma. In Period 3, participants were
again instructed to think about anything. ASD participants reported higher
ratings of anxiety, frequency of trauma-related thoughts, and attempted
suppression of trauma-related thoughts than non-ASD participants. Participants
who were given suppression instructions demonstrated a delayed increase in trauma
related thoughts in the period subsequent to suppression.
PMID- 9648333
TI - Dental fear with and without blood-injection fear: implications for dental health
and clinical practice.
AB - The relation between dental, blood and injection fear and oral health was
examined in 936 New Zealand 18-year-olds. Of the approximately ten percent (n =
96) of the sample who reported a dental fear, 1 in 10 also reported a fear of
blood and 53% a co-morbid fear of injections. Study members with dental fear
alone or co-morbid dental and blood or injection fear had significantly worse
oral health (i.e. greater caries experience) than a no-fear comparison group or
individuals with blood-injection fear only. Further, individuals with dental and
blood or injection fear had a significantly higher level of recent tooth decay
than individuals with dental fear alone. Time since last dental treatment also
tended to be highest in this group. Implications for dental health and practice
were discussed.
PMID- 9648334
TI - The prospect of predictive testing for personal risk: attitudes and decision
making.
AB - As predictive tests for medical problems such as genetic disorders become more
widely available, it becomes increasingly important to understand the processes
involved in the decision whether or not to seek testing. This study investigates
the decision to pursue the possibility of testing. Individuals (one group who had
already contemplated the possibility of predictive testing and one group who had
not) were asked to consider predictive testing for several diseases. They rated
the likelihood of opting for testing and specified the reasons which they
believed had affected their decision. The ratio of the numbers of reasons stated
for testing and the numbers of reasons stated against testing was a good
predictor of the stated likelihood of testing, particularly when the reasons were
weighted by utility (importance). Those who had previously contemplated testing
specified more emotional reasons. It is proposed that the decision process is
internally logical although it may seem illogical to others due to there being
idiosyncratic premises (or reasons) upon which the decision is based. It is
concluded that the Utility Theory is a useful basis for describing how people
make decisions related to predictive testing; modifications of the theory are
proposed.
PMID- 9648335
TI - Pain-related anxiety predicts non-specific physical complaints in persons with
chronic pain.
AB - Persons with chronic pain often report a range of physical symptoms beyond their
primary pain complaint itself. We predicted that non-specific physical symptom
complaints would correlate more strongly with pain-related distress than with
general measures of distress, and that they would contribute directly to
disability. Results from 210 adults with chronic pain showed that collateral
physical complaints are common in persons with chronic pain. Correlational
analyses showed that greater reporting of physical complaints was associated with
reports of higher pain severity, higher levels of depression, more cognitive,
escape/avoidance, fearful appraisal, and physiological symptoms of pain-related
anxiety and more physical and psychosocial disability. Regression analyses showed
that, with pain-related anxiety variables entered either before or after
depression, physiological symptoms of pain-related anxiety significantly
predicted physical complaints. In comparison with cognitive and somatic
depression symptoms physiological symptoms of pain-related anxiety were the
stronger predictor.
PMID- 9648336
TI - How do I look with my minds eye: perspective taking in social phobic imagery.
AB - This study explored perspective taking in social phobics' images of past anxiety
provoking social situations and non-social situations. For images of social
situations, social phobics were significantly more likely than non-patient
controls to take an observer perspective, viewing themselves as if from an
external point of view. In contrast, social phobics and controls did not differ
in the perspective taken in images of non-social situations, which were generally
viewed from a field perspective (seeing the situation as if looking out through
their own eyes). The clinical significance of these findings is briefly
discussed.
PMID- 9648337
TI - The long-term outcome of cognitive behaviour therapy for adults in routine
clinical practice.
AB - It is recognised that there is a comparative lack of evidence on the long-term
outcome of cognitive behavioural therapy for patients seen in ordinary clinical
settings, as opposed to research trials. This paper presents some data on the
outcome of 36 adult patients followed up an average of nearly two years after the
end of therapy in a National Health Service CBT clinic. Whilst the vagaries of
data collection in clinical practice mean that the generalisability of these
results is still tentative, they suggest that the outcome at the end of treatment
was generally well-maintained over the follow-up period, with most patients
maintaining fairly stable scores on the measures used, and the rest roughly
equally divided between those who deteriorated and those who improved further. A
high proportion of patients at follow-up reported that they were still using
various CBT strategies which they had learnt during therapy.
PMID- 9648338
TI - Weekly assessment of worry: an adaptation of the Penn State Worry Questionnaire
for monitoring changes during treatment.
AB - Development and validation of the Penn State Worry Questionnaire. Behaviour
Research and Therapy, 28, 487-495.] for weekly assessment of worry was evaluated
in a brief treatment study. Cognitive restructuring techniques were taught to 28
nonclinical high-worriers, 14 of whom served as a control group in a lagged
waiting-list design. Results showed that the Penn State Worry Questionnaire-Past
Week (PSWQ-PW) was highly reliable and substantially valid in the assessment of
both (a) weekly status of worry and (b) treatment-related changes in worry:
average Cronbach's alpha was 0.91; average convergent correlation with a past
week adaptation of the Worry Domains Questionnaire [Tallis, F., Eysenck, M. W.
and Mathews, A. (1992). A questionnaire for the measurement of nonpathological
worry. Personality and Individual Differences, 13, 161-168.] was 0.63 and pre
post improvement on PSWQ-PW showed a 0.71 correlation with the Questionnaire of
Changes in Experiencing and Behavior [Zielke, M. and Kopf-Mehnert, C. (1978).
Veranderungsfragebogen des Erlebens und Verhaltens. Weinheim, Germany: Beltz Test
Gesellschaft.]. It is concluded that the PSWQ-PW is a useful instrument for
monitoring pathological worry in experimental and applied settings.
PMID- 9648339
TI - [Cardiac accidents of locoregional anesthesia: experimental study of risk factors
with bupivacaine].
AB - Cardiac disorders are observed when excessive plasma concentrations of local
anaesthetics are reached, following for instance intravascular accidental
injection for epidural anaesthesia or brachial plexus block. Bupivacaine
particularly, which is one of the most used local anaesthetics, adversely affects
intraventricular conduction and cardiac contractile strength from the 3.0-4.0
micrograms/ml blood levels. Depression of conduction is especially to be feared,
for it can result in reentrant arrhythmias likely to degenerate into often fatal
ventricular fibrillation. Such accidents may sometimes occur at far lower
concentrations, subsequent to diffusion into systemic circulation from the
injection site (0.4-1.2 micrograms/ml). These accidents were probably due to
various factors which concomitantly intervene during the anaesthesia. We could
identify a number of these factors by associating them to an intravenous infusion
of bupivacaine (0.04 mg/kg/min after a loading dose of 1.00 mg/kg) in animals
(dogs and pigs) under electrocardiographic monitoring, in which conduction time,
monophasic action potential duration, effective refractory period and electrical
fibrillation threshold were determined in the ventricular fibres. The
electrophysiological changes due to bupivacaine may be enhanced by 1) dilution
hyponatremia (115-110 mmol/l) induced by a short (5 min) intravenous 10 ml/kg/min
infusion of hypotonic solution and/or hyperkalemia (7-8 mmol/l) induced by 0.05
mmol/kg/min infusion of potassium chloride; 2) the acceleration of cardiac
contractions (180-210 beats/min) induced by ventricular pacing; 3) mild
hypothermia (35-34 degrees C) induced by blood cooling in an extracorporeal
circuit; 4) myocardial ischaemia induced by complete temporary occlusion of the
left anterior descending coronary artery near its origin. The risk of cardiac
accidents, possibly severe, is therefore enhanced by each of these factors
capable of lowering the concentration required for their triggering and, of
course, the combination of two or several of them. On the contrary, the knowledge
of these factors should allow to prevent most of cardiac accidents of
locoregional anaesthesia.
PMID- 9648340
TI - [Reverse cholesterol transport and use of transgenic mice and rabbits to reveal
candidate genes for protection against atherosclerosis].
AB - Atherosclerosis is the leading cause of death in industrial societies. In France,
215 men out of 100,000 aged from 25 to 64 years old suffered of a myocardial
infarction in 1992 and due to this disease 67 men out of 100,000 died.
Hypercholesterolemia corresponding to a high LDL cholesterol level is an
important risk factor of myocardial infarction. Nevertheless a low cholesterol
level in the HDL fraction (frequently associated with an increase in
triglycerides concentrations) is a common abnormality found in patients with
confirmed coronary artery disease. Therefore, besides tentatives to reduce
triglycerides and LDL cholesterol levels, a therapeutical strategy consists in
increasing the serum HDL cholesterol concentration in order to improve the
"reverse cholesterol transport". Apo A-I is the major protein of HDL. Studies in
mice and rabbits transgenic for human apo A-I showed that overexpression of this
protein in these animals resulted in an increase in the HDL cholesterol level.
The serum of these animals contents a high concentration of particles containing
human apo A-I but not mouse apo A-II (LpA-I) and presents a higher ability to
induce cellular cholesterol efflux than the serum of the control mice. These
alterations result in a reduction of atherosclerosis development when these
animals are submitted to a cholesterol rich diet. Lecithin cholesterol acyl
transferase (LCAT) is a major enzyme in the metabolic cascade leading to the
return of cholesterol to the liver. The metabolic role of LCAT is to esterify the
free cholesterol of native HDL. Native HDL acquire free cholesterol during the
transfer of cholesterol from the cell membrane to the particle during the
cellular cholesterol efflux, which is the first step of the "reverse cholesterol
transport". Mice and rabbits transgenic for human LCAT have higher HDL
cholesterol levels. Transgenic rabbits but not transgenic mice are protected
against diet induced atherosclerosis development. Nevertheless, cholesterol fed
mice which are transgenic for both human LCAT and simian cholesteryl ester
transfer (CETP) protein do not develop atherosclerosis. This data indicates that
over production of LCAT reduces atherosclerosis when CETP is naturally (rabbit)
or artificially (CETP transgenic mice) expressed in the animals. Tentatives of
gene therapy in mice induced by adenovirus-mediated transfer of human apo A-I and
LCAT genes also increased circulating apo A-I and LCAT. Therefore apo A-I and
LCAT are two potential targets for gene therapy in patients with atherosclerosis
associated with a low HDL cholesterol level.
PMID- 9648341
TI - [Surgical hysteroscopy in the treatment of septate uterus: systemic treatment or
selective indications].
AB - OBJECTIVES: A retrospective study to evaluate the fertility rate after endoscopic
hysteroplasty in the case of a septate uterus. METHOD: From 1st January 1988-31st
December 1996, 93 patients showing a septate uterus were treated by endoscopic
hysteroplasty. The hospitalisation is short: one day surgery or out office. A
control of uterine cavity by hysteroscopy did next to two months. RESULTS:
Patients were evaluated after a period in excess of 6 months (6 months-8 years).
63 pregnancies were achieved amongst the 84 patients to be reviewed (75%). The
fertility rate achieved is higher amongst infertile patients (80.3%) compared
with that of sterile patients (64%). CONCLUSION: In the presence of septate
uterus the endoscopic hysteroplasty is an efficient treatment in the case of
secondary infertility and of unexplained sterility.
PMID- 9648342
TI - [Presentation of the Environmental-Health Prize 1997: Lyme borreliosis].
AB - Lyme borreliosis is an infectious disease, with multisystem involvement, due to a
spirochete known as Borrelia burgdorferi, transmitted to humans by ticks; its
recent emergence is, in part, the consequence of reforestation and the rise in
deer and rodents populations. The prevention and the treatment of this disease
are well standardized, the main risk being its misdiagnosis.
PMID- 9648343
TI - [Lyme borreliosis, emergent disease linked with the environment].
AB - After a short historical presentation of the discovery of the pathogen and its
vector, the authors present the current data on bacterial and acarologic
taxonomy. Then they describe their results to assess the mechanisms of
circulation of the bacteria in the forests of Ile-de-France, particularly in the
forest of Rambouillet. The combined study of abundance and infection frequency of
the vectors, small mammals and cervids leads to the characterization of periods
and areas of higher risk. The risk periods correlate with high density of I.
ricinus nymphs. The risk areas correspond to those of high density of cervids.
The role of reservoir of small mammals is confirmed, to the one of large mammals,
so debated, is clearly demonstrated.
PMID- 9648344
TI - [Recent aspects of monitoring the dosage of aminoglycosides and vancomycin].
AB - The narrow range of therapeutic serum concentrations of aminoglycosides and
vancomycin and the great variations in their pharmacokinetics from one person to
another makes it important to monitor patients at risk that are treated with
them. The technique of customizing dosages based on the population
pharmacokinetics enables an effective treatment to be rapidly established from a
few measurements of serum concentrations. Aminoglycosides may be given as single
daily doses because of their concentration-dependent activity. The high peak
concentration produces an enhanced, prolonged bactericidal activity, while a low
residual concentration reduces the risk of toxicity. The effect of vancomycin is
time-dependent. Giving it by continuous i.v. infusion maximizes the time during
which the serum antibiotic concentration is effective but non-toxic. Monitoring
serum concentrations can help reduce health care costs. But medical training in
pharmacokinetics is needed for the optimal use of these therapeutic tools.
PMID- 9648345
TI - [Membrane receptors and endocrine tumors: expression of vasopressin receptor V1
modulates the pharmacologic phenotype of adrenocortical tumors].
AB - A retrospective analysis of 26 adrenocortical tumors responsible for Cushing's
syndrome showed that vasopressin induced an ACTH-independent cortisol response in
seven cases (27%). In comparison 68 of 90 patients with Cushing's disease (76%)
had a positive cortisol response. The mRNA for the V1-type vasopressin receptor
was detected in normal adrenal cortex and in all tumors, and adenomas had higher
levels than carcinomas. One adenoma which had a brisk cortisol response in vivo,
also had in vitro cortisol responses that were inhibited by a specific V1
antagonist. In situ hybridization showed the presence of V1 mRNA in the normal
and tumoral adrenal cortex. We conclude that the vasopressin V1 receptor gene is
expressed in normal and tumoral adrenocortical cells. High--and not ectopic-
expression occurs in a minority of tumors which become directly responsive to
vasopressin stimulation.
PMID- 9648346
TI - [Interactions between central opioidergic and cholecystokininergic systems in
rats: possible significance for the development of of opioid tolerance].
AB - Numerous data suggest that cholecystokinin (CCK) acts as an opioid-modulating
peptide. Because pharmacological and behavioural studies have shown that CCK
reduces the analgesic effects of opioids, an opioid-mediated activation of CCK
containing neurones has been proposed to be responsible for the development of
opioid tolerance. In an attempt to directly assess this hypothesis, we have
examined, in naive or morphine-tolerant/dependent rats, the possible influence of
opioid-receptor ligands on--1 the release of CCK from spinal cord slices and--2
the extracellular levels of CCK in the frontal cortex in awake, freely moving
animals. Whereas the stimulation of mu or delta 1 receptors inhibited the release
of the peptide, the stimulation of delta 2 receptors increased CCK release.
Morphine also increased CCK release, via an action at delta 2 receptors. The
blockade of delta 1 receptors resulted in an enhancement of the peptide release,
suggesting that endogenous opioids probably exert inhibitory tonic influence on
CCK release through the stimulation of delta 1 receptors. In rats rendered
tolerant/dependent, the inhibitory effects of opioids on CCK release, due to the
stimulation of mu or delta 1 receptors, and the enhancing effect of delta 1
receptor blockade, were no longer present. In contrast, the delta 2-mediated
increase in CCK release persisted. Thus, in morphine-tolerant/dependent rats,
opioids apparently retain only their excitatory effects on CCK-containing
neurones. These data support the idea that morphine exerts an excitatory
influence on central CCKergic neurones, which could tend to reduce the analgesic
action of the alkaloid, and are in line with the hypothesis that morphine
tolerance/dependence is associated with an activation of CCK-containing neurones.
PMID- 9648347
TI - [Transient outward potassium current and repolarization of cardiac cells].
AB - The transient 4-aminopyridine-sensitive outward potassium current, Ito, is one of
the ionic membrane currents involved in the repolarization of cardiac action
potentials. It is present in several species (rat, dog, human) but not in guinea
pig ventricle. It induces both a marked lowering of the ventricular action
potential plateau level and an early repolarization wave in the ventricular ECG
complex of hypothermic rats. In dog ventricle where Ito is much shorter than the
action potential plateau it can induce only a transient initial repolarization
(notch). The distribution of Ito is heterogeneous across the dog left ventricular
free wall, the current being of sizeable amplitude in epicardial and
midmyocardial layers but absent in the endocardial layer. As a result,
ventricular action potentials exhibit a notch only in epicardial and mid layers.
Although the physiological role of Ito remains unclear, we suggest that it can
participate in the control of calcium current intensity by influencing the level
of the initial part of the plateau. In pathophysiological conditions, Ito may
exert unfavourable effects, specially during simulated ischemia when the notch
reaches the cellular repolarization threshold, thus inducing premature
termination of the action potential, an obvious cause of drastic electrical
heterogeneity and resulting severe arrhythmias. The current Ito is reduced in
moderate cardiac hypertrophy and dilatation and almost entirely suppressed in
severe hypertrophy. Ito is of larger amplitude in human atrial than in
ventricular myocytes. The heterogeneous distribution of Ito described in the dog
has also been found in human ventricles. Because Ito is markedly prolonged at low
temperatures it is suggested that it can be responsible for the early
repolarization wave (J wave) observed in the ECG of subjects submitted to
hypothermia.
PMID- 9648348
TI - [Use of hematopoietic stem cells from cord blood for allogenic transplantation in
man].
AB - Cells contained in umbilical cord blood collected after birth can be
cryopreserved and used for hematopoietic stem cells transplantation in patients
with severe hematological disorders. The first success has led to the development
of cryopreserved umbilical cord blood banks. More than 500 cord blood transplant
have been reported and more than 10,000 cord blood have been stored for use in
unrelated and related matched and mismatched transplants. European results show
that the number of hematopoietic stem cells present in one cord blood is
sufficient to permanently engraft most of the patients. Graft versus host disease
is decreased even in unrelated mismatched transplants.
PMID- 9648349
TI - [Aids and insurance].
PMID- 9648350
TI - [Xenogenic cellular therapy in man].
PMID- 9648351
TI - Commentary: making tuberculosis treatment available for all.
AB - Tuberculosis is one of the major public health problems that WHO has tackled
throughout the last 50 years. During the pre-clinical era treatment consisted of
the use of special diets, bed rest in sanatoria, and lung collapse therapy. The
case fatality rate 5 years after diagnosis was 50% and treatment in a sanatorium
was expensive and available only to the privileged few. The demonstration in the
1960s that ambulatory treatment of tuberculosis (one year of isoniazid and p
aminosalicylic acid) was as effective for patients and their families as
treatment in a sanatorium heralded the beginning of the end of the sanatorium era
and the beginning of the era of domiciliary treatment, which could be made widely
available to many people with the disease in countries where its prevalence was
high. Subsequent refinements in combination therapy led, in the 1960s, to the
development of intermittent regimens and, in the 1970s, to short-course regimens
following the introduction of rifampicin. The currently recommended WHO strategy
for tuberculosis control is termed DOTS, which is being promoted globally to free
the world from this millennia-old scourge.
PMID- 9648352
TI - Research steps in the development and evaluation of public health interventions.
AB - Presented is a conceptual framework for planning intervention-related research.
Altogether, nine steps in the process of developing and evaluating public health
interventions are specified. This process is dynamic and iterative, and all steps
are not always required, or need follow in sequence. The framework can be used to
set research priorities by verifying where there is sufficient knowledge to move
forward and by identifying critical information gaps. It can also help select
appropriate research designs, as each step is characterized by certain types of
studies. Greater effort is required to move beyond descriptive epidemiological
and behavioural studies, to intervention studies. Field trials of public health
interventions require particular attention as they are often neglected, despite
their significance for public health policy and practice.
PMID- 9648353
TI - Priority during a meningitis epidemic: vaccination or treatment?
AB - From November 1995 to May 1996, a meningitis epidemic occurred in northern
Nigeria. More than 75,000 cases and 8440 deaths (case fatality rate (CFR), 11%)
were recorded. Medecins sans Frontieres, in cooperation with the Nigerian
government, carried out an assistance programme (support to case management,
surveillance and mass vaccination) in three states (Bauchi, Kano, Katsina) where
75% of cases occurred. Cost analysis of this assistance in Katsina State reveals
that case management and mass vaccination were efficient: US$ 35 per case treated
and US$ 0.64 per vaccination. There was, however, a remarkable difference in cost
effectiveness between the two strategies. The cost per death averted by improved
case treatment was estimated to be US$ 396, while the cost per death averted by
vaccination was estimated to be US$ 6000. In large part this difference is
attributed to the late start of vaccination: more than 6 weeks after the epidemic
threshold had been passed. During meningitis epidemics in countries where
surveillance systems are inadequate, such as in most of sub-Saharan Africa,
curative programmes should have priority.
PMID- 9648354
TI - Measuring hunger in the Russian Federation using the Radimer/Cornell hunger
scale.
AB - Compared in the study are the results obtained using the Radimer/Cornell hunger
scale to measure the prevalence of hunger in random samples of mothers and their
households in the Russian Federation and in the USA in 1993. The 12 items in the
scale measured hunger at three levels: household, women, and children. If the
mother answered positively to one of the four items at a particular level, hunger
was established for that level. The prevalence of hunger in the Russian
Federation was very high: approximately 77% of the women surveyed, 70% of the
households, and 32% of the children were classified as hungry. The corresponding
estimated prevalences of hunger in New York State in 1993 were 46.8%, 25.9% and
18.3%. In both surveys, children were the least likely to be classified as hungry
and, if they were, their mothers and households were almost always hungry. In
both surveys, the hunger scale proved to have criterion-related validity. Basic
indicators of household socioeconomic and demographic well-being were highly
related to the three levels of hunger. The higher level of hunger in the Russian
survey can be explained by the very low incomes. Further study of the nutritional
status of the Russian population is recommended.
PMID- 9648355
TI - Prognostic scores for use in African meningococcal epidemics.
AB - Current WHO guidelines for the case management of meningococcal infections during
epidemics in developing countries often cannot be applied, largely because of the
limited health resources in such countries. Several scoring scales based on
clinical and laboratory features in numerous combinations have been developed for
the management of meningococcal infections in developed countries, and these have
facilitated early identification of patients with fulminant disease and thus
early intervention and reduction in mortality. Unfortunately such scoring scales
are not appropriate for use in developing countries. We identified hypotension,
tachycardia, tachypnoea, delay in capillary refill time, coma, absence of neck
stiffness and petechiae and/or purpura as simple prognostic factors of
meningococcal disease. Two scores were developed: score I, which includes all
seven prognostic factors, had a sensitivity and specificity of 80% and 94%,
respectively. Score II, which excluded hypotension, had a sensitivity and
specificity of 73.3% and 89.7%, respectively. Quick and simple scoring scales are
therefore not only applicable but useful for the case management of patients in
meningococcal epidemics in developing countries.
PMID- 9648356
TI - Renal dysfunction from cadmium contamination of irrigation water: dose-response
analysis in a Chinese population.
AB - In a cadmium-contaminated area in China and a nearby non-contaminated area, 342
persons were selected for studies of a possible relationship between cadmium dose
(i.e. total cadmium intake) and response in terms of renal dysfunction. An
increase in urinary excretion of beta-2-microglobulin (UB2M), adjusted for age
and sex, was used as an indicator of the response. A statistically significant
relationship was found between measured cadmium concentrations in whole blood
(range; < 3.5 to > 15 micrograms/l) and UB2M, and there was a statistically
significant linear trend. Also, cadmium in urine (< 4 to > 16 micrograms/g
creatinine) and UB2M displayed a statistically significant positive relationship
when the total data set was analysed for males and females. The relationship
between a dose index (obtained from calculated cumulative absorbed doses over a
lifetime) and UB2M was statistically significant. The results of this first study
on dose-response relationships in a Chinese population are similar to those
observed in other populations.
PMID- 9648358
TI - Bacterial contamination of the lacteal contents of feeding bottles in
metropolitan Sao Paulo, Brazil.
AB - Reported are the results of a study in Sao Paulo, Brazil, to evaluate the
bacterial contamination of the lacteal contents of feeding bottles prepared in
urban households of low (LSE) and high (HSE) socioeconomic groups, involving 100
and 32 mothers of infants, respectively. Samples of the lacteal contents of the
feeding bottles were cultured and the medians (25th and 75th percentiles) of the
counts (bacteria per ml) were significantly higher in the LSE group: mesophilic
bacteria, 555,000 (17,250-4,350,000) in the LSE group and 1615 (20-500,000) in
the HSE group; coliforms, 2400 (19-150,000) in the LSE group and 7 (0-7800) in
the HSE group. Escherichia coli was isolated from 26% (26/100) of the samples
from the LSE group and from 6% (2/32) of those from the HSE group (P = 0.03). In
the HSE group, higher coliform counts were associated with foodhandlers other
than the mother, lower levels of maternal education, the use of pasteurized milk,
and the addition of ingredients other than milk. In the LSE group, feeding
bottles prepared using tap water and those prepared for infants aged over 6
months had higher coliform counts. In general, the feeding bottles prepared in
the households studied were heavily contaminated, especially in the LSE group.
PMID- 9648357
TI - Causes of childhood deaths in Bangladesh: results of a nationwide verbal autopsy
study.
AB - While knowledge of causes of deaths is important for health sector planning,
little is known from conventional sources about the causes of deaths in
Bangladesh. This is partly due to deficiencies in the registration system and
partly because few deaths are attended by qualified physicians. The present study
was undertaken to update the information available on causes of deaths among
under-5-year-olds, taking advantage of advances in verbal autopsy methodology and
of the national Bangladesh Demographic and Health Survey conducted in 1993-94.
About 25% of the deaths were associated with acute lower respiratory infections
(ALRI) and about 20% with diarrhoea. Neonatal tetanus and measles remained
important causes of death, and drowning was a major cause for 1-4-year-olds.
Research and programmes to enable mothers to identify ALRI cases, particularly
pneumonia, and to encourage timely and appropriate care-seeking and strengthening
of ALRI case management at the primary care facilities are important priorities.
While promotion of oral rehydration for watery diarrhoea and antibiotic treatment
for dysentery should continue, broader preventive interventions including
provision of safe water and sanitation, and improvements in personal hygiene
require more attention. Further intensification of immunization programmes and
innovative experimental interventions to reduce childhood from drowning should be
designed and tested.
PMID- 9648359
TI - Estimation of the prevalence and causes of infertility in western Siberia.
AB - The study examined the epidemiology and causes of infertility in Tomsk, Western
Siberia, using methodological approaches recommended by WHO and was based on the
findings for a randomly selected sample of 2000 married women aged 18-45 years.
Among the respondents, 333 couples were considered infertile since they had not
conceived after 12 months or more of unprotected intercourse. This group of
infertile couples was offered comprehensive clinical investigations but only 186
couples completed them. The infertility rate in Tomsk was 16.7%, being caused by
diseases of the female reproduction system in 52.7% of the couples and by male
reproductive diseases in 6.4%. In 38.7% of couples, both spouses suffered from
infertility, while in 2.2% of cases the cause of infertility was not determined.
Among the causes of female infertility, secondary infertility dominated (12.9% of
all the women questioned), while primary infertility affected 3.8% of the women.
The most frequent causes of female infertility were disturbances to tubal patency
(36.5%) and pelvic adhesions (23.6%). Endocrine pathology was found in 32.8% of
cases. The most frequent cause of male infertility was inflammatory disease of
male accessory glands (12.9%). In 8.6% of cases infection resulted in obstructive
azoospermia. Varicocele was registered in 11.3% of cases, and idiopathic
pathospermia in 20.9%. Inflammatory complications among females were 4.2 times
more frequent than among males.
PMID- 9648360
TI - Approaches to control sexually transmitted diseases in Haiti, 1992-95.
AB - Despite major obstacles, activities to control sexually transmitted diseases
(STDs) were initiated in Haiti in 1992 in collaboration with local
nongovernmental organizations. The approaches included review of available local
data, assessment of STD case management practices and constraints, and
development of specific STD control activities at the primary health care level,
such as systematic screening of all pregnant women for syphilis and improved
comprehensive syndrome-based STD case management. The activities included conduct
of local studies, presentation and dissemination of results to key audiences,
training of health care providers, improvement of local capacities, and consensus
building on implementation of STD control approaches. STD awareness and case
management improved considerably; for example, 69% of the clinicians interviewed
reported correct STD treatments in the north-eastern primary health care centres
in 1995, compared with < 10% in 1992. At the end of the project, national STD
case management guidelines were developed by consensus between the various
organizations and the Ministry of Health. Lessons learned included the importance
of local data generation and of communication and collaboration with various
institutions for consensus-building, the need for continued training, and field
supervision to ensure behaviour change among STD care providers. A national STD
control programme should be implemented as soon as possible in both the public
and private sector. External funding will remain critical to control this
important public health problem in Haiti.
PMID- 9648361
TI - [What determines the choice of health care treatment in the town of Contonou
(Benin)?].
AB - Households in Contonou show a clear preference for modern medicine. Self
medication is the first choice, followed by use of private practices, which are
growing in importance in Benin as treatment options. This preference for private
medicine seems to meet a demand that is not covered by the public services, which
occupy the third place among treatment options. The hospital and the practitioner
of traditional medicine are the last resort where the other choices have not
produced the expected outcome. The choice of self-medication is determined by the
patient's assessment that the illness is not serious, by the habit of using a
certain treatment in response to a familiar symptomatology, and by the desire to
avoid the expense of a consultation. The recourse to other options is connected
with the geographical accessibility of the places of consultation, the cost of
care and treatment, the reception accorded to patients at the place of
consultation, the seriousness of the illness and, to a lesser degree, the
relations of kinship with the health personnel in the services visited. The
choice between the available health services lies principally between private
clinics and public health centres. There is therefore a need to consider the
operation of public health centres and the quality of the care they provide since
this would enable those responsible for health service organization and planning
to make better informed choices. At the same time, the state should encourage its
research bodies to study the operation of the private sector in the light of the
importance of this type of care in the treatment chosen by households.
PMID- 9648364
TI - Legionnaires' disease in Europe, 1996.
PMID- 9648362
TI - Haemoculture as a tool for diagnosing visceral leishmaniasis in HIV-negative and
HIV-positive patients: interest for parasite identification.
AB - Between May 1993 and June 1996, 65 adults infected with human immunodeficiency
virus (HIV) and 30 HIV-negative patients (8 children and 22 adults) from the
Mediterranean region with symptoms that included at least fever were examined for
Leishmania. A total of 128 bone marrow and 128 peripheral venous blood samples
were taken and cultured on NNN medium. At the initial diagnosis, 14 (6 HIV
positive and 8 HIV-negative) of 15 patients with a positive blood culture also
had a positive bone marrow culture. Two patients (1 HIV-positive and the other
HIV-negative) had a positive bone marrow culture but a negative blood culture.
During post-therapeutic check-ups, 7 out of 8 patients with a positive blood
culture (6 HIV-positive and 1 HIV-negative) also had a positive bone marrow
culture. On the other hand, three patients (2 HIV-positive and 1 HIV-negative)
had a positive bone marrow but a negative blood culture. Relapses were more
frequent (9/65 vs. 3/30) and the demonstration of Leishmania in the blood was
commoner (6/65 vs. 2/30) in the HIV-positive than the HIV-negative patients.
Stocks were identified by their isoenzymes: MON-1 from four HIV-positive and
eight HIV-negative patients, MON-28 from one HIV-positive patient and MON-29 from
another. For each patient, the same zymodeme was found in bone marrow and blood
cultures, both at initial diagnosis and at follow-up.
PMID- 9648363
TI - Selected gastrointestinal pathologies in tropical sub-Saharan Africa.
AB - Doctors need to be well informed about differences in the presentation of certain
diseases in tropical and temperate climates. In this article the characteristics
of some gastrointestinal diseases, as they recur in sub-Saharan Africa, are
briefly reviewed. Diseases of the stomach--including ulcertaion and cancer--are
uncommon in Africa, although duodenal ulcer is common all over the tropics. In
contrast, colorectal cancer is an extremely rare illness in sub-Saharan Africa,
while hepatocellular carcinoma is much commoner than in Europe or North America
and the very high incidence of this tumour in tropical countries is cause for
concern.
PMID- 9648365
TI - Arboviruses in the Australian region, 1990 to 1998.
AB - Arboviruses continue to be major human pathogens in the Australian region. This
report provides a summary of the activities of these viruses over the past eight
years, and comments on new findings relevant to their respective ecologies. Of
particular interest and concern is the propensity of these viruses to spread. The
examples discussed include the initiation of dengue epidemics in north Queensland
by virus imported in viraemic travellers; the spread of Japanese encephalitis
virus to the Australasian region and its probable enzootic establishment in the
south-west of Papua New Guinea; the potential spread of Ross River virus to other
countries, as demonstrated by the 1979-80 outbreak in the South Pacific, and the
recent occurrence in military personnel from the United States of America after
an exercise; and the recent spread of Barmah Forest virus into Western Australia.
PMID- 9648366
TI - Ross River virus infection in the north-west outskirts of the Sydney basin.
AB - In early 1997, 69 cases of Ross River virus infection were reported in the north
western outskirts of Sydney. This represents a substantial increase over the
maximum of 12 cases reported in any one year since 1991. The majority of cases
(71%) are thought to have been locally acquired. This is the first reported
outbreak of Ross River virus infection in this area and highlights the need for
metropolitan health services to be vigilant about a disease that has primarily
been associated with rural and semirural areas in New South Wales.
PMID- 9648367
TI - A presumptive case of fatal Murray Valley encephalitis acquired in Alice Springs.
AB - A presumptive case of Murray Valley Encephalitis (MVE) acquired in Alice Springs
in March 1997 is reported. The patient subsequently died in Mackay. The diagnosis
of Murray Valley Encephalitis was supported by the detection of flavivirus IgM in
cerebrospinal fluid. Low titres of IgM specific to Murray Valley Encephalitis and
Alfuy were detected in a single serum sample. The patient's travel movements
indicate that his infection was acquired in the Alice Springs vicinity. This
conclusion was further supported by the detection of Murray Valley Encephalitis
activity in sentinel animals in the area and by the presence of large numbers of
the principal mosquito vector of Murray Valley Encephalitis in the Northern
Territory.
PMID- 9648368
TI - Dengue or Kokobera? A case report from the top end of the Northern Territory.
AB - In early April 1998, the Centre for Disease Control in Darwin was notified of a
possible case of dengue which appeared to have been acquired in the Northern
Territory. Because dengue is not endemic to the Northern Territory, locally
acquired infection has significant public health implications, particularly for
vector identification and control to limit the spread of infection. Dengue IgM
serology was positive on two occasions, but the illness was eventually
presumptively identified as Kokobera infection. This case illustrates the
complexity of interpreting flavivirus serology. Determining the cause of
infection requires consideration of the clinical illness, the incubation period,
the laboratory results and vector presence. Waiting for confirmation of results,
before the institution of the public health measures necessary for a true case of
dengue, was ultimately justified in this case. This is a valid approach in the
Northern Territory, but may not be applicable to areas of Australia with
established vectors for dengue.
PMID- 9648369
TI - Three cases of dengue 1 virus infection from islands in the Gulf of Thailand.
AB - Three Australian tourists who recently travelled to islands in the Gulf of
Thailand developed febrile illnesses associated with myalgias, thrombocytopenia,
and atypical lymphocytosis. Dengue 1 virus was isolated from all three patients.
The patients' clinical features and serological and virological investigations
are presented. These cases highlight the need for awareness of dengue amongst
travellers and the preventive precautions required when visiting endemic regions.
After the urgent exclusion of malaria, dengue should be considered in the
differential diagnosis of febrile persons who have recently returned from endemic
regions.
PMID- 9648370
TI - Dengue 3 in Cairns: the story so far.
PMID- 9648371
TI - A case of infant botulism in South Australia.
PMID- 9648372
TI - National immunisation coverage--interpreting the first three quarterly reports
from the ACIR.
PMID- 9648373
TI - Hepatitis A--the neglected sexually transmissible disease.
PMID- 9648374
TI - Communicable diseases surveillance.
PMID- 9648375
TI - [Pregnancy outcome after in vitro fertilization].
PMID- 9648376
TI - [Estrogen-progestin contraception and cardiovascular diseases: the end of
polemics on the third generation].
PMID- 9648377
TI - [Perimenopause: limits and pitfalls of colposcopic evaluation].
PMID- 9648378
TI - [Management of late induced abortions in France].
AB - In France, the painful ignored question about the taking into charge of
termination of pregnancy demands requires a careful examination for appraising
the situation realistically as much as for considering humanly acceptable
answers. About 6000 women cope every year with this dramatic problem which is
often medically settled in Holland, Great-Britain and Spain. As it is a question
of serious psychological circumstances after 20 years dealing with abortion
medicalization, a status quo, deplored by most of family planning professionals,
cannot be accepted. A regional health service dealign with late abortions, once
or twice a week, would be sufficient to resolve most of the problems. Knowing in
other respects that two thirds of termination of pregnancy demands do not take
more than 15 weeks of amenorrhoea.
PMID- 9648379
TI - [Delayed deliveries in multiple pregnancies: is this reasonable?].
AB - Delivery of viable fetus with a long interval delay is an unusual occurrence.
There is no clear attitude among obstetricians for such cases. We report a case
of retention of the second and the third triplet after the delivery of the first
one at 24 weeks of amenorrhea and 3 days. The duration of the retention was 6
days. Only the third infant survived. We attempt to outline the difficulties in
managing such pregnancies.
PMID- 9648380
TI - [Breech presentation: management (304 cases)].
AB - BUT: Try to precise the optimal management in 1997 face a breech presentation.
METHOD: Between January 1991 and December 1995, 304 cases of breech presentations
were listed at the maternity of Pavillon Victor Olivier (Lille). From these 304
breech presentations, all parities blended, the authors have analysed the mode of
delivery of these patients, distinguishing the para one from the multiparous
women and the preterm babies from the other babies. From this study and a review
of the literature, were discussed the criterions which can help the practitioner
to determine the mode of delivery of these fetus. RESULTS: The results show a
cesarean section (cs) rate of 51% (41% of first intention cs and 10% of second
intention cs were realized only for primiparity + breech presentation and 67% of
the para one women benefited from a first intention cs 8.72% of vaginal
deliveries were complicated, and 5 fetal injuries were noted without sequel. On
296 live new-borns, only 2 cases of fetal death were perhaps due to the vaginal
delivery. Fetal mortality is principally reliable at the prematurity and the
congenital malformations, but finally, not due to mode of delivery. CONCLUSION:
The difficulty is to determine rigorous criterions of selection to authorize a
vaginal delivery without spoil the fetal pronostic. The major criterions are a
perfect radiopelvimetry, an estimated fetal weight < 3800 g for the para one
women and < 4300 g for the multiparous woman, a well flexed fetal head, favorable
obstetric conditions ond the absence of maternal or fetal complications. The
primiparity is not an indication of systematic cesariean section.
PMID- 9648381
TI - [Influence of weight and distribution of adipose tissue in functional
hyperandrogenism].
AB - Approximately half the women with the polycystic ovary syndrome (PCOS) are obese
or overweight. Obesity and body fat distribution have independent roles in the
development of hyperandrogenism in PCOS. Most obese and normal weight PCOS are
insulin resistant and hyperinsulinemic. Moreover, a significant positive
correlation exists between the degree of hyperandrogenism and that of
hyperinsulinism. The pathogenetic role of obesity may involve different
mechanisms, the major one being the hyperinsulemic state, since insulin is
capable of stimulating ovarian androgen secretion and controlling androgen
metabolism and transport in peripheral tissues. Abdominal body fat distribution
in obese women with PCOS amplifies the degree of hyperandrogenism and related
clinical symptoms and signs. Both loss of body weight and/or the reduction of the
degree of hyperinsuliemia, induced by diet or insulin-sensitizing drugs, have
important effects, since they reduce blood androgen levels and can improve
ovulation and clinical signs of hyperandrogenism.
PMID- 9648382
TI - [Comparison of laparoscopic and laparotomy colposuspension in the treatment of
urinary stress incontinence. Comparative study of 72 matched cases].
AB - The aim of this study was to compare the results of open retropubic (OC) and
laparoscopic (LC) colposuspension to the Cooper's ligament (Burch operation). We
matched retrospectively 72 LC and OC according to their ages, the type of
associated operations and the clinical stages of their urinary incontinence. We
excluded associated prolapsus, previous surgical procedure for urinary
incontinence, maximal urethral closure pressure lower than 30 cms of water and
instability of the detrusor. We estimated the comparability of our two series
about the other criteria which have an effect upon the post operative results in
literature. The mean follow up was 17 months for LC and 46 months for OC. LC
operative time was longer than (Mean: LC: 89 minutes, OC: 42 minutes), women
considered LC less aching than OC. They needed less postoperative analgesia,
mostly given only just the day of the procedure. LC length of hospitalization and
return to normal activity was shorter than OC (Mean: LC: 3 days--OC: 6, 7 days;
LC: 15 days--OC: 21 days). The graphs of the subjective cure and improvement
rates made according to the Kaplan-Meier method could be compared with the log
rank test. (Cure after one year: LC 79%, OC 69%--Improvement after one year: LC
85%, OC 82%--Cure after two years: LC 68%--OC 64%--Improvement after two years:
LC 80%--OC 75%).
PMID- 9648383
TI - [Influence of sexual steroids on behavior in the postmenopause].
PMID- 9648384
TI - [Treatment of pelvic pain in gynecology].
PMID- 9648385
TI - [Pain therapy in palliative medicine].
AB - The large majority of patients being managed in palliative medicine are suffering
from incurable, far advanced and progressive cancer. An overall treatment
strategy not only includes the treatment of physical symptoms but also integrates
the psychological, social and spiritual problems of the patients and his/her
relatives. The most stressful physical symptom is pain, which may be so severe as
to be intolerable. With the judicious use of opioids and adjuvant substances,
this can be managed satisfactorily. The opioid of choice is oral morphine. The
value of oral oxycodone and hydromorphone has not yet been fully established, and
it remains to be seen what role they will play in the future. These two
substances are expected to become available in Germany in 1998.
PMID- 9648386
TI - [Pain therapy in pediatric oncology].
AB - Malignancy-related pain is of similar frequency in children and adolescents as in
adults. In children too evaluation of pain intensity, character and location is
the basis for individually adapted pain therapy. The choice of medication is
determined by the pathophysiological cause and the intensity of the pain. In
addition to non-opioid analgesics, tramadol is used for moderate, and morphine
for severe, pain. In the case of neuropathic pain, coanalgesics are employed. If
oral treatment with morphine is no longer possible, pain pumps for continuous
parenteral treatment must be used in children too. Provided the appropriate
medical care is possible, parenteral treatment with potent opioids can also be
applied at home. In children, every effort must be made to make painful
diagnostic and therapeutic measures as painfree as possible.
PMID- 9648387
TI - [Phytotherapy. 3: Use in diseases of the respiratory tract].
PMID- 9648388
TI - [How "ethics arguments" hinder research. With Buxus sempervirens against AIDS?].
PMID- 9648389
TI - [New therapeutic possibilities in pulmonary emphysema. Conservative therapy-
surgical lung volume reduction--lung transplantation].
AB - The spectrum of therapeutic possibilities in pulmonary emphysema has recently
been expanded by surgical lung volume reduction. Improvements in surgical
technique have now lowered the mortality rate of the procedure to less than 5%,
thus providing a chance of prolonging survival and improving the quality of life
of severely ill patients in need of oxygen. To date, experience has been gained
with this procedure in several thousands of patients in the U.S.A. and Europe,
some groups of patients have now been followed up for about three years. The
procedure is not recommended for use in patients with genetically determined
alpha 1-antitrypsin deficiency. Surgical bullectomy is practiced when individual
bullae affect more than 50% of a lung. In special cases, the possibility of lung
transplantation should also be considered. In addition to the invasive
approaches, survival, but in particular quality of life, can also be improved by
conservative procedures. These include medical anti-obstructive treatment, the
early use of antibiotics in the case of infections, but also physiotherapeutic
measures such as pursed-lip breathing and exercises to strengthen diaphragma.
Palliative measures in advanced stages are long-term oxygen therapy and in
special cases non-invasive self-ventilation.
PMID- 9648390
TI - [Smoking cessation in unavoidable. Interview by Dr. rer. nat. Renate Leinmuller].
PMID- 9648391
TI - [Phytotherapy. 2: Use in cardiovascular diseases (and dementia)].
PMID- 9648392
TI - [Hypertension: pro and contra fixed combination therapy. Pro].
PMID- 9648393
TI - [Hypertension: pro and contra fixed combination therapy. Contra].
PMID- 9648394
TI - [Guide for general practice. Much evidence favors broad use of fixed
combinations].
PMID- 9648395
TI - [Alpha-1 blockers for therapy of essential hypertension. 2 clinical studies with
bunazosin].
PMID- 9648396
TI - [Understanding and properly treating Lyme borreliosis. Family physician study in
the USA reveals large management deficits].
PMID- 9648397
TI - [Gonarthrosis--current aspects of therapy with glucosamine sulfate (dona200-S)].
AB - For many years glucosamine sulfate has been successfully used in the therapy of
osteoarthritis. Today's importance of the treatment with glucosamine sulfate is
even increasing. Glucosamine sulfate meets all standards of an efficient and well
tolerated drug. This is proven by experimental as well as clinical studies, in
which glucosamine sulfate was tested in accordance with the current state of
scientific research. The results show that glucosamine sulfate will lead to long
lasting pain reduction and functional improvement by means of increasing
anabolical mechanisms, reducing the activity of proteolytic enzymes and by its
antiinflammatory effect. Since this therapeutical effect is not due to an
inhibition of the prostaglandin synthesis, treatment is not accompanied by the
known unwanted side effects. Glucosamine sulfate is very well tolerated by
patients of all ages under short-term as well as long-term treatment.
PMID- 9648398
TI - [Localization of the gene for 4 hereditary multiple exostoses families].
AB - We investigated 11 families with hereditary multiple exostoses (EXT) by linkage
analysis using 8 short-tandem-repeat (CA)n polymorphic markers on chromosomes 8,
11 and 19. The Lod score in four families indicated that the gene responsible for
EXT is located in the pericentromeric region of chromosome 11.
PMID- 9648399
TI - [The genetic analysis of amplitude of progesterone secretion in serial blood
collection from tail in min sows].
AB - 28 adult Min sows (3-7 parities), represented 9 sire families were selected to
conduct the continual blood collection from the tail for two hours at the
interval of ten minutes between 9:00-11:00 in the morning on the sixth day after
the last mating. The content of progesterone was assayed by radio-immunological
assay. The amplitudes of the secretion of progesterone were generated by the
procedure of HORM fft. exe complied by the author. It is difficult to get a
reasonable conclusion from the content analysis, because the content varied
widely between different points of blood collection in single sow. After Fourier
conversion, the heritability of amplitude for the fifth partial wave was high (h2
= 0.932); middle for the basal, 2nd and 3rd partial waves; lower for others. This
supported the idea that prolific sows had more active secretion of progesterone
in luteal cells. The coexist of low and high heritability components in amplitude
of progesterone secretion showed that the activities of progesterone secretion
were influenced by both the genetics and environments. The genetic correlation of
basal, 1st, 5th partial waves were negative, the others were positive, with the
litter size and litter size alive. It showed that the reproductive performance of
Min pigs were not expressed perfectly, as the balance of secretion of
progesterone did not reach the best. The genetic correlation of all partial waves
with duration of estrus was negative which supported that the progesterone
suppresses the estrus. The genetic correlation of 3rd, 5th partial waves were
stronger than others, but selection for 5th partial wave would make high
responses than the 3rd wave, because the genetic correlation of 3rd partial wave
with litter size and litter size alive was positive, therefore, the more
appropriats method of selection for progesterone was adopted, the better results
would be achieved in the improvement of indirect selection response for litter
size.
PMID- 9648400
TI - [Genetic relationships of Nyctereutes procyonopides: as inferred from random
amplified polymorphic DNA analysis].
AB - Random amplified polymorphic DNAs (RAPDs) were used to investigate genetic
relationships of eight raccoon dogs (Nyctereutes procyonopides). Using 28
arbitrary primers (10 bp), about 130 RAPD markers were observed in each
individual. The average, maximum, and minimum genetic distance among 8 raccoon
dogs are 11.20%, 14.93%, and 2.94% respectively. Our molecular phylogenetic trees
constructed by UPGMA and NJ methods suggest that those 8 Chinese raccoon dogs may
be divided into 4 clusters: (1) Guangxi raccoon dog, (2) Anhui raccoon dog, (3)
Shaanxi raccoon dog, (4) Yunnan and Vietnam raccoon dog. Guangxi raccoon dog is
more closely related to Anhui raccoon dog than to Yunnan-Vietnam raccoon dog. If
the Yunnan-Vietnam cluster is a valid subspecies, it is reasonable to give the
Guangxi, Anhui and Shaanxi clusters the same classification status as that of the
Yunnan-Vietnam Cluster.
PMID- 9648401
TI - [Studies on late replication bands of giant panda (Ailuropoda melanoleuca)
chromosomes].
AB - Using the cultured giant panda (Ailuropoda melanoleuca) lymphocytes as
experimental material, we carried out the terminal marking on the chromosomes
which were in replication by adding BrdU (a final concentration: 10
micrograms/ml) about four hours before harvesting the cells. The chromosomes
marked by BrdU were proceeded by staining with acridine orange solution (0.05%),
irradiated by ultraviolet and counter-stained by Giemsa, we obtained clear
chromosomes replication patterns. According to the different replication bands,
every chromosome's characteristics in late replication behavior could be
identified. In the two X chromosomes of female individual, one X chromosome is
obviously much later than the other one. Especially in the large area near
centromere on the long arm of late replicating X chromosome. In the male
individual, there is also a large area on the long arm of chromosome Y which
replicates very late, but the end of long arm of chromosome Y replicates much
earlier.
PMID- 9648402
TI - [Px gene of rice-field eels primed in situ labeling].
AB - Peroxidase (Px) gene of rice-field eels (Monopterus albus) was successfully
localized to the segments of two bivalents, 8q15-q26 and 11q32-q37 with
digoxigenin labeled primed in situ labeling (PRINS) technique, which is utilized
for localization of single copy gene of fish for the first time. Our results
demonstrated the possibility of mapping genes in fish by the DNA probes of other
species and PRINS technique.
PMID- 9648403
TI - [Study on the induction of pco promoters from Escherichia coli with copper and
other metal ions].
AB - Two copper inducible promoters in the pco determinant of Escherichia coli were
studied by determining the luciferase activity of report vector pUCD615. The
results showed that in the absence of pBIN19pco, providing copper resistance
genes in trans, the maximum induction for both PpcoA lux fusions was observed at
5 mmol/L CuSO4 and PpcoA box was a stronger promoter than PpcoA long. There were
two peaks in the bioluminescences of both PpcoE-lux fusions induced with
increasing copper concentration, the first peak was observed at about 0.5 mmol/L
CuSO4, the second peak, also the maximum induction, was observed at about 5
mmol/L CuSO4, and PpcoE long was a stronger promoter than PpcoE box. The results
indicated that the PpcoE promoter was a much stronger promoter than PpcoA
promoter. The results also showed that the copper box was very important and
essential to pco promoters, since both of the Ppco short-lux fusions failed to
show any luciferase activity when they were induced with copper. In the presence
of pBIN19pco, the maximum inductions of all of the Ppco-lux fragments were
observed at 6 mmol/L CuSO4 and they were much higher than those observed in the
absence of pBIN19pco, and the results also indicated that the cells were able to
resistant to much higher copper concentration in the presence of pBIN19pco than
in the absence of that. Zn2+ and Ni2+ could be inducers for all of the fragments
and Zn2+ was a better inducer than Ni2+, and Cd2+ and Ag+ did not induce the pco
system.
PMID- 9648404
TI - E&M coding.
PMID- 9648405
TI - Cancer risk assessment in the community practice setting.
PMID- 9648406
TI - Advances in diagnosis and therapies for breast cancer.
AB - Major achievements in the field of breast cancer research have occurred in the
last year. Improved treatment options with reduced toxicities, better methods of
diagnosing disease at a low stage and determining women who are at genetic risk,
and the prospect of breast cancer prevention will hopefully translate into
further reductions in breast cancer incidence and mortality.
PMID- 9648407
TI - Advancements in radiotherapy and improved outcomes in prostate cancer.
PMID- 9648408
TI - Progress and promise in pediatric oncology.
PMID- 9648409
TI - Latest trends and applications of stem cell transplantation.
PMID- 9648410
TI - Current trends in the management of melanoma.
PMID- 9648411
TI - Head and neck oncology: what's new.
PMID- 9648412
TI - Hospice resources in south Carolina.
PMID- 9648413
TI - Why is CDA in the publishing business?
PMID- 9648414
TI - CDA board approves new fluoride supplementation dosage schedule.
PMID- 9648416
TI - The changing face of disability insurance and how it affects you.
PMID- 9648415
TI - New guidelines for antibiotic prophylaxis approved. Canadian Dental Association.
PMID- 9648417
TI - A Ukraine odyssey.
PMID- 9648418
TI - Interim storage of avulsed permanent teeth.
AB - This literature review examines the effects of extra-alveolar duration and
storage conditions on the healing of the periodontal ligament (PL) of avulsed
teeth following replantation. A critical assessment of the so-called
"reconstitution theory" for PL cells is also presented. The ideal treatment for
an avulsed tooth is immediate replantation (i.e. less than five minutes).
Unfortunately, immediate replantation is not the norm, and most avulsed teeth
experience delayed replantation. The greatest risk to the vitality of the PL
cells attached to the root of an avulsed tooth is desiccation. Not surprisingly,
storage media affect PL healing. Storing avulsed teeth in an isotonic liquid is
superior to dry storage. Numerous studies support the use of Modified Eagle's
Medium, Hank's Balanced Salt Solution (HBSS), ViaSpan, saline, milk, and saliva
as storage media. A recent study has suggested that chicken egg white may also
prove to be a suitable storage medium for avulsed teeth. Of these media, only
saliva is always present at the scene of an accident, however. Milk can usually
be obtained on short notice, but even 10 minutes of desiccation can affect the
outcome of replantation. From a practical standpoint, milk packed in ice seems to
be the best alternative for the temporary storage of avulsed teeth, due to its
wide availability and the minimal detrimental effects it has on PL cells. There
is no evidence to support the suggestion that HBSS or any other media will
"reconstitute" the PL cells when the extra-alveolar duration of avulsed teeth is
greater than 30 minutes.
PMID- 9648419
TI - [Endopore: a new generation of implants].
AB - The Endopore implant system has gained popularity since it was first
commercialised. Developed at the University of Toronto, its unique design is
characterized by a partial porous coating and a tapered, truncated-cone,
endosseous root-form. These features allow for ease of placement, a faster
healing period, the use of shorter implants, and greater resistance to torque
(due to bone ingrowth in the porous coat). This article discusses the design and
fabrication of the Endopore implant. The surgical procedure as well as the main
advantages of this new type of implant are also considered.
PMID- 9648420
TI - The part-time clinical instructor in the undergraduate dental clinic.
AB - Currently, part-time dental instructors do not receive formal training in
education. According to the recent literature, some instructors may not be aware
of all the options available to them in the clinic. It has been observed, for
example, that instructors have demonstrated the greatest effectiveness while
acting as facilitators rather than as educators. These instructors are able to
incorporate their position as role models into their teaching. Dental departments
must understand that the tone established in the clinic has a significant impact
on the quality of their students' learning experience. This tone arises out of
open dialogue between instructors and their students. The complexities of
successful teaching can only be conquered when more information is provided to
part-time staff.
PMID- 9648421
TI - Management of accidental and iatrogenic injuries to the dentition.
AB - This article discusses the restoration of teeth with extensive fractures
extending beyond the attachment of the periodontal ligament, as well as the
treatment of iatrogenic perforations observed during post space preparation.
Various treatment procedures and their limitations are described, based on the
authors' many years of clinical experience.
PMID- 9648422
TI - Effects of diversion and reperfusion of pancreaticobiliary juice on amylase
release from isolated rat pancreas.
AB - Diversion of pancreaticobiliary juice from the small intestine results in
resetting of the normal negative-feedback regulation of exocrine pancreatic
secretion. The mechanism by which this process occurs is not well understood. To
examine this regulatory process, we investigated the effects of
pancreaticobiliary juice diversion and reperfusion on exocrine pancreas using
isolated rat pancreatic acini. Two groups of rats were surgically prepared for
pancreaticobiliary juice diversion and reperfusion. Both groups received a liquid
diet via a duodenal cannula and saline by intravenous infusion for 24 hours
following surgery. Forty-eight hours after the surgery and infusions, the rats
were sacrificed, and acinar cells were quickly isolated from each pancreas.
Amylase release from isolated acini was measured in response to doses of
cholecystokinin octapeptide (CCK-8) and carbachol. Acinar cell receptor binding
was measured by using CCK-8 labeled with iodine 125 and N-tritium-methscopolamine
bromide as radioligands. Amylase release in response to both CCK-8 and carbachol
was significantly decreased in the diversion group when compared with that of the
reperfusion group. Receptor binding sites of CCK-8 and methscopolamine bromide
were similar in the diversion and reperfusion groups. The results suggest that
cholecystokinin- and carbachol-mediated amylase response is affected by
pancreaticobiliary juice diversion through a process that most likely involves
alteration of post-receptor-mediated intracellular signaling pathways.
PMID- 9648423
TI - Spontaneous resolution of a plasma cell granuloma in a 9-year-old.
AB - A previously healthy 9-year-old white boy presented with a 13-lb weight loss over
a period of 4 weeks and a 4.5-cm mass in the right lung. Histology was compatible
with a plasma cell granuloma, which is the most common benign childhood lung
tumor. Surgical management with segmental or wedge resection is the usual
standard of care in this situation. However, it has been suggested that with a
confirmed histologic diagnosis surgical resection is not warranted. This patient
was managed conservatively. Repeat computed tomography scan 6 weeks later
revealed significant resolution of the lesion, and at 7 months the lesion had
totally resolved. Spontaneous resolution of this lesion has been rarely described
in pediatric populations.
PMID- 9648424
TI - Emergency departments and abuse: policy issues, practice barriers, and
recommendations.
AB - The abuse of women has reached epidemic proportions. There are an estimated 12
million abused women in the United States. Reported cases of abuse, however,
range from 2 to 4 million. Less than 15% of these women ever seek medical care.
Of women who do seek care, an estimated 75% use the emergency department, often
presenting with complaints not readily suggestive of abuse. Reports indicate,
however, that emergency departments consistently identify less than 10% of all
abuse cases. In 1991 and 1992, the Joint Commission on Accreditation of
Healthcare Organizations established standards for emergency departments to
develop policies and procedures for the identification, treatment, and referral
of female and elderly victims of abuse. Virtually all emergency medicine
professional societies have official policies to encourage development of
protocols for abuse identification and management. The American Medical
Association and the Department of Health and Human Services have likewise
developed guidelines to help emergency departments achieve these national health
care objectives. Currently, less than 50% of all emergency departments have
established algorithms to address abused women who present to the emergency
department for treatment. This article reviews current health policy, examines
the impediments to the detection of abuse in the emergency department, and
recommends mechanisms to enhance the awareness of abuse among emergency
department personnel.
PMID- 9648425
TI - Use and safety of aspirin in the chemoprevention of colorectal cancer.
AB - Colorectal cancer is the third leading cause of cancer-related mortality and a
significant public health problem in the United States. Aspirin and other
nonsteroidal anti-inflammatory drugs reduced the incidence of colorectal cancers
and related mortality by 30% to 60% as well as the incidence of colonic adenomas.
This effect is presumably due to an inhibition of cyclooxygenase 2, an inducible
enzyme involved in the synthesis of prostaglandins. Prostaglandins are increased
in colorectal neoplasms. Aspirin's effect appears to be dose related and enhanced
by long-term exposure. Two prospective studies, however, failed to show a
protective benefit of aspirin in colorectal cancer. When used long term, aspirin
has significant adverse effects and is poorly tolerated. The gastrointestinal
toxicity of aspirin is dose related, but even low doses of aspirin (75 mg per
day) when used regularly result in significantly higher gastrointestinal
toxicity, manifested by melena, hematemesis, and peptic ulcer disease, in aspirin
users compared with nonusers. Furthermore, some studies indicate an increased
risk of hemorrhagic strokes in aspirin users. Presently, aspirin should not be
recommended for the primary chemoprevention of colorectal cancer in the general
population due to significant risks of serious cerebrovascular and
gastrointestinal adverse effects associated with long-term aspirin use.
PMID- 9648426
TI - [Antibiotic therapy in eradicating Helicobacter pylori infections].
PMID- 9648427
TI - [Recent topics on Helicobacter pylori--Historic background and problems caused by
bacteria].
PMID- 9648428
TI - [Studies on Helicobacter pylori].
PMID- 9648429
TI - [Pathophysiological mechanism of Helicobacter pylori infections].
PMID- 9648430
TI - [Pathophysiological mechanism of Helicobacter infections--host factors].
PMID- 9648431
TI - [Helicobacter pylori infections in animal models].
PMID- 9648432
TI - [Gastritis due to Helicobacter pylori].
PMID- 9648433
TI - [Peptic ulcer due to Helicobacter pylori].
PMID- 9648434
TI - [Helicobacter pylori and stomach cancer, lymphoma, and MALToma].
PMID- 9648435
TI - [Helicobacter pylori and non-ulcer dyspepsia].
PMID- 9648436
TI - [Diseases suspected to have relationship to Helicobacter pylori].
PMID- 9648437
TI - [Diagnosis of Helicobacter pylori infections by endoscopy, bacterial culture
method, and rapid urease test].
PMID- 9648438
TI - [Diagnosis of Helicobacter infections by serodiagnosis, analysis of serum
pepsinogen, and urea breath tests].
PMID- 9648439
TI - [Efficacy of antibiotic therapy in eradicating Helicobacter pylori].
PMID- 9648440
TI - [Problems following antibiotic therapy for eradication of Helicobacter pylori].
PMID- 9648441
TI - [Present status of vaccine therapy for Helicobcter pylori infection].
PMID- 9648442
TI - [Topics on Helicobacter pylori (discussion)].
PMID- 9648443
TI - [Case of diabetic diarrhea successfully treated by cholestyramine].
PMID- 9648444
TI - [Case of primary aldosteronism associated with heart and kidney failure].
PMID- 9648445
TI - [Calcified aneurysm of sinus of Valsalva in the aged].
PMID- 9648446
TI - [Case of acute respiratory failure due to polyarteritis nodosa].
PMID- 9648447
TI - [Case of tubercular constrictive pericarditis with right atrial thrombosis].
PMID- 9648448
TI - [Vibrio vulnificus infections].
PMID- 9648449
TI - [Present status and future prospects in development of blood substitutes].
PMID- 9648450
TI - [Hyperlipidemia and arteriosclerosis].
PMID- 9648451
TI - [Changing concept and definition of osteoporosis].
AB - History of osteoporosis dates back to prehistoric era and no real progress in the
understanding of osteoporosis was made until 1900 AC when Roentgen discovered X
ray to make bone visible in vivo. From this time to 1950 when Albright and many
others opened way to the pathophysiology of osteoporosis as one of the metabolic
bone diseases, X-ray picture was the only tool to assess osteoporosis. Subsequent
biochemical, epidemiological and endocrinological approach clarified the risk
factors and pathophysiology of osteoporosis in the modern age. Treatment and
prevention of osteoporosis also became feasible based on these development. Such
a rapid progress in the understanding of osteoporosis also caused an inevitable
confusion in the concept of osteoporosis.
PMID- 9648452
TI - [Pathogenesis of osteoporosis and risk factors].
AB - Osteoporosis is defined as a disease with low bone mineral density (BMD) and the
increased probability for non-traumatic fractures in elderly. BMD in the elderly
is theoretically determined by the BMD reached in younger era and the rate of
bone loss in the later life. Both of peak bone mass and bone loss rate are known
to be affected by environmental factors as well as genetic factors. In addition,
both factors are assumed to interact each other. Prevention and treatment of
osteoporosis would be fascilitated by understanding both of these factors.
PMID- 9648453
TI - [Genetic studies in osteoporosis].
AB - Osteoporosis is one of the complex disease which has many responsible fractors to
develop this disease. Among the causative factors for osteoporosis, genetic
background is believed as the most important factor for osteoporosis. In 1994,
Morrison et al reported their pioneering work looking at the close relationship
between VDR genotype and bone mass. This report has generated a considerable
amount of interest and conflict. The reasons for these conflicts are depending
upon the nature of osteoporosis. Namely, the genetic association to the cause of
osteoporosis is polygenic. Furthermore, the contribution of a gene to achieve low
bone mass is polyphasic. For example, estrogen-receptor gene polymorphisms may
show varied importance in the different stage of women's life span. The
environmental factors may interefere the penetration of a gene effect and the
presence of the other gene effect may also blunt the effect of the candidate
gene. To overcome these difficulties in the research work to search osteoporosis
gene, we have pay keen attention to the selections of the method of gene analysis
and the subjects. The specific gene marker showed the possibility to predict the
effect of the treatment of osteoporosis. This may indicate the marker gene itself
or the other gene(s) linked with this marker gene regulate the biological
response to the treatment. So, gene markers may utilize not only in the field of
epidemiological studies but also in clinical practice in near future.
PMID- 9648454
TI - [Morphology of bone remodeling].
AB - In this review, first the basic structure of bone and the histological and
cytological characteristics of bone remodeling are reviewed. Then, topics on the
ultrastructural and cytochemical characteristics of the biological
mineralization, such as matrix vesicle and advanced collagen mineralization, are
discussed. The recent advances in the understanding of the fine structural and
cytochemical characteristics of bone cells in bone remodeling and their role in
the regulation of bone metabolism, with special focus on the ultrastructural and
cytochemical evidences of cell to cell, cell to metrix interaction of bone cells
are also reviewed.
PMID- 9648455
TI - [Regulatory mechanisms of bone remodeling].
AB - Bone tissues continuously renew themselves to maintain their bone volume and
mechanical strength. Sequence of the cellular events at the site of bone
remodeling is as follows: (1) Activation; osteoclast progenitors are activated
and differentiated. (2) Resorption; osteoclasts resorb a certain volume of bone
by removing bone matrix and mineral. (3) Formation; osteoblasts differentiate and
form new bone. The cellular coupling in space and time between osteoclastic
resorption and osteoblastic formation is regulated not only by systemic hormones
(estrogen, PTH, calcitonin, or vitamin D etc.) and local factors (TGF-beta, BMPs,
IGFs, prostaglandins, interleukins, or TNF-alpha, etc.), but also by mechanical
stress. We review the various regulators for bone remodeling and comment on the
regulatory mechanism of bone remodeling.
PMID- 9648456
TI - [Recent advances in researches on bone formation--role of BMP in bone formation].
AB - Recent advances in action of bone morphogenetic protein (BMP), a member of TGF
beta superfamily, in the differentiation process of mesenchymal cells such as
osteoblasts, chondrocytes, bone marrow stromal cells and muscle cells have been
reviewed. BMPs induce osteoblast differentiation of various types of cells
including undifferentiated mesenchymal cells, bone marrow stromal cells and
preosteoblasts. BMPs not only inhibit myogenic differentiation but also convert
differentiation pathway of some myogenic cells into an osteoblast lineage. The
regulatory mechanism of BMP action discovered in the process of early
embryogenesis is also reviewed; noggin, chordin and follistatin inhibit BMP
action by specifically binding to BMPs.
PMID- 9648457
TI - [Recent advances in biology of bone resorption].
AB - Bone resorption is a unique process which requires function of highly specialized
cells, i.e., osteoclasts, Osteoclasts are terminally differentiated multinuclear
cells that originate from multipotent hematopoietic stem cells and are closely
related to the monocyte/macrophage lineage. Recent advances in molecular
biological techniques and development of useful experimental systems both in
vitro and in vivo have made it possible to identify several factors essential to
osteoclast differentiation or function under physiological and/or pathological
conditions. Such factors include transcription factors such as c-Fos and PU.1,
cytokines such as IL-6 and TNF-alpha, and other various molecules such as
tyrosine kinases and adhesion molecules. This review will focus on recent
progress in our understanding of osteoclast biology.
PMID- 9648458
TI - [Localization and function of calcium-sensing mechanism in bone cells].
AB - Elevation of extracellular calcium has been shown to inhibit osteoclastic bone
resorption and stimulate proliferation and chemotaxis of osteoblasts. Therefore,
calcium released by bone resorption may have important roles in the coupling of
bone resorption and bone formation. Although both osteoclasts and osteoblasts
have calcium-sensing mechanisms, the responsible molecule in these cells seems to
be different. Functional and histological studies show that calcium-sensing
mechanism in osteoclasts is a ryanodine receptor-like molecule in plasma
membrane. In contrast, calcium-sensing mechanism in osteoblasts has similar
functional property to parathyroid calcium-sensing receptor (CaSR), but is a
different molecule from CaSR. In addition, several bone marrow cells express
CaSR. The elucidation of the identity and the physiological roles of these
calcium-sensing mechanisms would give us a more clear view of bone remodeling.
PMID- 9648459
TI - [Bone matrix proteins].
AB - Bone matrix is composed of collagen and non-collagenous proteins. The collagen is
mainly type I collagen. Characteristics of bone collagen are in posttranslational
modifications and utilization of transcriptional elements in the promoter. The
non-collagenous proteins are acidic Ca-binding proteins: bone Gla protein(BGP),
bone sialoprotein (BSP), osteopontin, osteonectin etc. BGP and BSP are specific
to bone, and other proteins are present also in non-mineralized tissues. BGP
functions in suppression of excessive mineralization. BSP and osteopontin are
sialoproteins containing a RGD cell-attachment sequence and poly(acidic amino
acid) sequences. BSP is present in sites of bone formation. Osteopontin is
involved in attachment of osteoclasts to bone surface.
PMID- 9648460
TI - [CBFA1/PEBP2 alpha A].
AB - A transcription factor, Cbfa1/Pebp2 alpha A, which belongs to runt-domain gene
family, is preferentially expressed in the osteoblast lineage. Cbfa1/Pebp2 alpha
A-deficient mice lacked both intramembranous and endochondral ossification
completely. The differentiation of osteoblast was blocked, and the maturational
disturbance of osteoclasts was also observed in the mutant mice. Further, the
Cbfa1/Pebp2 alpha A expression in nonosteoblastic cells induced osteoblastic
markers in vitro. These data demonstrate that Cbfa1 is an essential transcription
factor for osteoblast differentiation and bone formation. Heterozygously mutated
mice in the Cbfa1/Pebp2 alpha A locus showed the similar phenotype with
cleidocranial dysplasia, which is an autosomal inherited disease. And the
mutations of CBFA1/PEBP2 alpha A locus were identified in the patients with
cleidocranial dysplasia.
PMID- 9648461
TI - [Osteoclastogenesis inhibitory factor (OCIF)/OPG].
AB - A novel cytokine termed osteoclastogenesis inhibitory factor (OCIF) was purified
to homogeneity from conditioned medium of human embryonic lung fibroblasts. OCIF
is a heparin-binding basic glycoprotein with Mr of 60 kDa for a monomer and 120
kDa for a homodimer. OCIF specifically inhibits osteoclastogenesis in vitro and
increases bone mineral density and bone volume in normal rats. The cloning of
OCIF cDNA revealed that OCIF is a soluble member of the tumor necrosis factor
receptor (TNFR) superfamily consisting of four cystein-rich domains, two death
domain homologous regions (DDHs), and C-terminal basic domain. Mutational
analysis of OCIF revealed that N-terminal portion of OCIF consisting of four
cystein-rich domains is sufficient to inhibit osteoclastogenesis. OCIF inhibits
osteoclastogenesis by binding to the sites expressed on osteoblastic cells and
interrupting cell-to-cell signaling between osteoblastic cells and osteoclast
progenitors.
PMID- 9648462
TI - [Cloning and expression of 25-hydroxyvitamin D3-1 alpha-hydroxylase gene].
AB - A full-length cDNA for the rat kidney mitochondrial cytochrome P450 mixed
function oxidase, 25-hydroxyvitamin D3-1 alpha-hyroxylase, was cloned from a
vitamin D-deficient rat kidney cDNA library and subcloned into the mammalian
expression vector pcDNA 3.1(+). When 1 alpha-hydroxylase cDNA was transfected
into COS-7 cells, they expressed 25-hydroxyvitamin D3-1 alpha-hydroxylase
activity. The sequence analysis showed that 1 alpha-hydroxylase cDNA consisted of
2469 bp in length and contained an open reading frame encoding 501 amino acids.
The expression of 1 alpha-hydroxylase mRNA was greatly increased in the kidney of
vitamin D-deficient rats. In rats with the enhanced renal production of 1 alpha,
25-dihydroxyvitamin D3 (rats fed a low Ca diet), expression of 1 alpha
hydroxylase mRNA was greatly enhanced in the renal proximal convoluted tubules.
These results clearly demonstrate that the expression of 1 alpha-hydroxylase is
regulated at a transcriptional level. The DNA flanking the 5'-sequence of the
mouse 1 alpha-hydroxylase gene has been cloned and sequenced. The promoter has 3
potential CRE sites, 2 perfect and 1 imperfect AP-1 sites, while no DR-3 was
detected. Parathyroid hormone stimulates this promoter-directed synthesis of
luciferase by 17-fold, while forskolin stimulates it by 3-fold. These results
indicate that parathyroid hormone stimulates 25-hydroxyvitamin D3-1 alpha
hydroxylase by acting on the promoter of the 1 alpha-hydroxylase gene.
PMID- 9648463
TI - [Establishment of cultured cells sustaining bone metabolism and their application
for osteogenesis in vivo].
AB - Osteoblasts, osteoclasts and osteocytes respectively, play important roles
responsible for bone metabolism. These cells were cultured in vitro by many
researchers, and considerably contributed to recent basic research on bone
metabolism. Especially MC3T3E1-cells, cloned mouse osteoprogenitor cells, can
perform bone formation-process in culture. Furthermore, several osteoblastic cell
line including our SaM-1 cells were established from rodent calvaria,
osteosarcoma, and human bone or periosteum. Also, osteoclasts are actually formed
from human bone marrow cells, as well as rodent bone marrow cells, recently. It
has become effective that the results obtained by using normal human cultured
cells apply to human bone metabolism in vivo.
PMID- 9648464
TI - [Criteria and classification for diagnosis of osteoporosis in Japan].
AB - Osteoporosis has become one of the most serious medical and social problems in
Japan, as the number of elderly people is increasing. Osteoporosis should be
diagnosed early and treated properly to maintain the patients' quality of life
before associated fractures occur. The Japanese society for bone and mineral
research prepared the criteria for diagnosis of osteoporosis in 1995 and modified
them in 1996. Here, we explained the 1996's modified criteria and described the
actual way to diagnose osteoporosis. Low bone mass is evaluated by radiographic
osteopenia or bone mineral density in lumbar body. We have to exclude the other
disorders showing low bone mass.
PMID- 9648465
TI - [Recent development and clinical application of bone mineral measurements].
AB - Over the past decade, methodologies for the assessment of bone mineral density
have markedly progressed, so that any sites of the skeleton now can be measured
with high degree of accuracy and precision with safety. The number of devices
distributed in Japan rapidly increased for the last 5 years and the total number
installed nationwide reached over 7000 as with 1998. There are variety of
techniques: microdensitometry (MD) or radiographic absorptiometry (RA), single X
ray absorptiometry (SXA), dual X-ray absorptiometry (DXA), quantitative CT (QCT),
peripheral QCT, and quantitative ultrasonometry (QUS). There are, however, no
such single technique as to fulfill the entire clinical requirements, since the
time of initiation of bone loss, and the speed of bone loss are quite different
from site to site of the skeleton, so that the correlations of bone density
measured by each technique are not sufficiently high (gamma = 0.5-0.8) to predict
BMD of other bones by measuring one bone. Since the relatively large amounts of
data on the prediction of fracture (hip, spine and others) by these techniques
have been accumulated, a specific guideline regarding the appropriate application
of these techniques, including multiple combination measurements, should be
established based on the worldwide consensus.
PMID- 9648466
TI - [Photodensitometry].
AB - Photodensitometry was developed by several investigators. This technique makes
possible bone mass measurements from radiographs of the peripheral skeleton, most
commonly the metacarpal and phalangeal bones. More recently, with the advent of
computerized image processing, photodensitometry has become more precise and
gained new respect for use in the diagnosis of osteoporosis. In addition, recent
studies in which radiographic absorptiometry was used have demonstrated that the
detection of accelerated bone loss in the early menopause with this technique is
comparable to other densitometry techniques. Being cost effective, easy to
perform, and universally available, all makes photodensitometry an increasing
attractive option for non invasive bone assessment in both research and clinical
practice.
PMID- 9648467
TI - [X-ray absorptiometry].
AB - Bone mass measurements are essential in the diagnosis of osteoporosis, the
monitoring of its progression, and the evaluation of therapeutical responses.
Among various methods of bone mass measurements, single- and dual-X-ray
absorptiometry, SXA and DXA, have shown excellent fundamental performance. In
this paper, the principles of SXA and DXA; i.e., factors of fundamental
performance, such as precision, data-acquisition, and radiation dose, the
practice of DXA, recent advances in DXA, such as the lateral spine scan, the
measurement of body composition, application to BMD measurement of the bones of
small animals and at sites of metal implants, morphometry of the spine, and
geometrical measurement in the proxial femur, and clinical applications to
osteoporosis were particularly reviewed.
PMID- 9648468
TI - [Ultrasound bone densitometry of os calsis].
AB - In the last couple of years, Ultrasound bone densitometry (QUS: Quantitative
ultrasound) have been developed which allow the assessment of fracture risk
caused by osteoporosis. QUS are particularly promising since they are simple,
inexpensive, portable, non-invasive and they do not subject the patient to any
ionising radiation. Additional investigations that assess innovative QUS
techniques in well defined research settings are important to determine and
utilize the full potential of this technology for the benefit of early detection
and monitoring of osteoporosis.
PMID- 9648469
TI - [Quantitative X-ray computed tomography].
AB - Quantitative X-ray Computed Tomography (QCT) has an advantage to be able to
determine three-dimensional bone density of lumbar vertebral body compared with
dual energy X-ray absorptiometry (DXA) method. We introduced the high
reproductable QCT method as a simplified manual operation avoiding simultaneous
imaging of both patients and bone mass phantoms. The coefficient of variation of
values measured by phantom study was 0.6% for 7 years in our hospital. In
measuring of 144 healthy Japanese women, the bone mineral density of lumbar spine
was most likely to be decreased linealy with age.
PMID- 9648470
TI - [Analysis of trabecular microstructure using micro-computed tomography].
AB - Micro-computed tomography (micro-CT) is a special CT to examine biopsy bone
samples or small animal bones in vitro, and it can provide high resolution images
(20-30 microns) precisely representing the two-dimensional and three-dimensional
microstructure of the trabecular bone. The quantification of trabecular
connectivity and anisotropy, which is believed to be strongly related to the bone
strength, can be done with micro-CT. In comparison with histomorphometry and
scanning electron microscopy, micro-CT has the advantage of requiring less
efforts and time. Besides, micro-CT provides higher resolution than micro
magnetic resonance. So far, micro-CT is believed to be the best method to analyze
the three-dimensional structure in vitro.
PMID- 9648471
TI - [Biochemical markers of bone metabolism].
AB - Markers of bone metabolism can be utilized for selection of treatment and/or
evaluation of the treatment, and possibly decision-making to start treatment.
Resorption markers are sensitive to detect changes in bone metabolism but show
higher day-to-day variation, and formation markers are less sensitive but show
less fluctuation. Among these markers, deoxypyridinoline, NTx, and CTx are
utilized for short-term judgement of efficacy during the early phase of anti
resorptive treatment, such as bisphosphonate and hormone replacement therapy. The
coefficients of day-by-day variations in these resorption markers are 8-14%.
Thus, 20 (approximately 30)% or more change in marker levels may be necessary to
detect the efficacy in individual patients on anti-resorptive therapy. The
formation markers can be utilized for monitoring the degree of excessive
suppression during the late phase of treatment by anti-resorptive treatment,
possibly later than 6 months following initial treatment.
PMID- 9648472
TI - [Guidelines for clinical use of drugs for involutional osteoporosis].
AB - Guidelines for clinical use of drugs for involutional osteoporosis will be
released soon in Japan. Seven different types of drugs for osteoporosis are in
market for clinical use in Japan. Those includes calcium, estrogens, anabolic
steroids, calcitonins, active vitamin D3, ipriflavon, and etidronate. The
guidelines recommend to clarify the risk factors in each patient before to start
administration of drug. Patients with osteopenia are basically recommended to be
followed without any drug treatment, but, patients with osteoporosis are
generally recommended to be treated with drug after evaluation of risk factors.
After menopause, inhibitors of bone resorption would be recommended as a first
choice drug. For monitoring effects of treatment, bone mass measurement is so far
the first choice, but bone metabolic markers would be used as well.
PMID- 9648473
TI - [Treatment of osteoporosis by active vitamin D].
AB - Supplementation of active vitamin D has been thought to be reasonable for those
who convert insufficiently vitamin D to active form, especially for senile
persons. Treatment of osteoporosis by vitamin D are accepted as not only
supplementation of vitamin D but also direct activation of bone turnover. Several
previous clinical trials suggest active vitamin D prevents fractures more
effectively rather than the increase of the bone mass. The calcium intake of
Japanese people is less than that of Western countries, and many of Japanese have
the vitamin D receptor genotype which is more responsive to vitamin D. Therefore,
it is probable that active vitamin D is more effective for Japanese than Western
people.
PMID- 9648474
TI - [Calcitonin].
AB - Calcitonin is a potent inhibitor of osteoclastic bone resorption and has been
widely used for the treatment of osteoporosis. Nasal calcitonin, instead of
injectable form, is more popular in Europe and United States, while only
injectable form has been approved in Japan. The regimen, dose, frequency is
remarkably different from study to study, and the standard regimen has not been
established for osteoporosis. Fifty to 100 units of salmon calcitonin has been
used daily intramuscularly in Europe. Recent trial using nasal calcitonin has
shown the similar effects on the bone as the injectable form although the actual
resorptionis not so high. In Japan, once weekly 20 units if eel calcitonin
analogue injection has been approved for osteoporosis. After administration in
the form of either nasal or injectable preparation, peak serum concentration
reaches more than 100 pg/ml, far exceeding 10(-11) M, at which level osteoclast
bone resorption is rapidly impaired with disappearance of actin ring formation.
It is reflected by the decrease of urinary pyridinoline cross-links excretion.
Consecutive treatment with calcitonin reduces the calcitonin receptors on the
surface of osteoclasts as well as osteoclast precursors, while they are still
TRAP positive, suggesting that they retain bone resorbing activity. That may be
one of the mechanisms of escape phenomenon. We are not sure whether daily
administration of calcitonin can avoid the escape phenomenon and can maintain the
bone volume. The standard preparation should be determined by the longer clinical
trials with new bone markers and bone mass measurement as the endpoints.
PMID- 9648475
TI - [Role of estrogen in the pharmacotherapy of osteoporosis].
AB - Since approval by the Food and Drug Administration of bisphonate and calcitonin
for the prophylaxis of osteoporosis, estrogen preparations are no longer the only
drugs effective against this disease. However, because of their effects on
systems other than bone, estrogens remain the gold standard of osteoporosis
therapy in postmenopausal women, and health care workers should reacknowledge the
benefits of estrogen therapy. Although several recent, multicenter double-blind
studies have reported that estrogens increase bone mineral density (BMD) and
prevent fractures, further substantiating their clinical efficacy, the effects of
estrogens on BMD and fracture risk can vary widely among individuals. Rather than
being used indiscriminately, estrogens should therefore be used in selected
patients most likely to benefit from such therapy. Treating such patients will
improve drug compliance, promote continued treatment, and therapy firmly
establish the role of estrogen therapy.
PMID- 9648476
TI - [Vitamin K2].
AB - Vitamin K2 is a known vitamin to promote post-translational modification of
vitamin K-dependent protein such as osteocalcin and blood coagulation factors.
The effects of vitamin K2 on cortical bone mineral density in osteoporosis has
been shown in the phase III DBT trial which had been reported several years ago.
However, until now there is no available data regarding to the effect of vitamin
K2 on vertebral bone mineral density (LBMD) and on fracture prevention. Thus, a
two years randomized open trial to examine the effects of vitamin K2 on LBMD and
the fracture prevention in a total of 167 osteoporotic patients had been carried
out. The LBMD in vitamin K2 treated group was maintained for 2 years while, that
in the control group was deceased to -3% during 2 years observation. The
vertebral fracture incidence in the control group was 0.212 +/- 0.038 events/year
and that in the treated group was 0.098 +/- 0.029 (p = 0.0186). Vitamin K2
treated group showed significantly lower Glu-osteocalcin level suggesting that
vitamin K2 contributed to increase in post-translational modification of
osteocalcin. When the treated group was divided into two groups: Group 1 showed
low serum Glu-osteocalcin level and Group 2 maintained high Glu-osteocalcin level
despite vitamin K2 administration. The LBMD in group 1 significantly higher than
that in the Group 2. This may indicate that sufficient tissue supply of vitamin
K2 is the limiting factor to increase in LBMD. Furthermore, patients with Apo E4
phenotype showed less response in LBMD comparing to that in the patients without
Apo E4. In conclusion, vitamin K2 is effective to maintain trabecular BMD in
osteoporosis and effectively prevent future fracture. However, some part of the
patients didn't respond to vitamin K2 treatment. Therefore, we have to develop
the more practical way(s) to predict the effectiveness of vitamin K2 treatment in
osteoporosis.
PMID- 9648477
TI - [Bisphosphonates: pharmacology and use in the treatment of osteoporosis].
AB - Bisphosphonates are attractive antiresorptive drugs for osteoporosis. The only
compound available in Japan is the first-generation bisphosphonate, etidronate.
Etidronate adsorbes to the surface of hydroxyapatite crystals, and can slow bone
mineralization and inhibit bone resorption. It has a narrow therapeutic window
between these two actions, so that long-term continuous administration is not
feasible. The intermittent use of etidronate produces a positive effect on bone
mass. But the response varies directly with the rate of bone turnover at
baseline. In high turnover osteoporosis there could be a gain in bone mass, but
it reaches a plateau after 2 to 3 years. In normal or low turnover osteoporosis
bone mass is stabilized but does not increase. However, the long-term effect of
bisphosphonates on bone strength is not known.
PMID- 9648478
TI - [Ipriflavone].
AB - Ipriflavone (7-isopropoxyisoflavone), a non-hormonal isoflavone derivative, is
currently used in several countries for prevention and treatment of
postmenopausal osteoporosis. This compound is devoid of estrogenic activity in
humans, but increases the activity of estrogens. Ipriflavone has been shown to be
effective in reducing bone turnover rate mainly through an inhibition of bone
resorption, and has been effect to stimulate of bone formation. Inhibitory effect
of ipriflavone on bone resorption has been demonstrated both directly by the
activation of mature osteoclast and the formation of new osteoclasts by
stimulating estrogen-induced calcitonin secretion by thyroids in vivo. There are
some evidence that ipriflavone has direct effect on bone formation. Several
clinical studies have demonstrated that bone mineral density (BMD) was increased
or maintained in patients treated with ipriflavone. Recently, a large
multicentral study, Ipriflavone Multicenter European Fracture Study (IMEFS), was
designed in order to investigate the efficacy of ipriflavone on the prevention of
vertebral and the effect on BMD in women with postmenopausal osteoporosis.
PMID- 9648479
TI - [Recent progress in orthopaedic managements of osteoporosis-related fractures].
AB - Recent progress in orthopaedic treatment of osteoporosis-related fractures was
reviewed. In the femoral neck fractures, the bipolar prosthesis reduces
acetabular erosion or central migration, and press-fit stem or cemented stem
lowers the incedence of the stem sinking. In thorocanteric fractures, compression
hip screws are most commonly used, however, in the cases of unstable fractures
with severe osteoporosis, it is difficult to start weight-bearing within a few
weeks of surgery because varus deformites or translations at the fracture site
sometimes occur. To avoid this disadvantage, the gamma nail has been found to be
more effective. In paralysis due to burst fractures of the osteoporotic spine,
surgical decompression and spinal instrumentation is the established response. A
special orthosis named 'rucksack type orthosis' has been devised and is used for
patients who have back pain due to anterior bending posture of the trunk. In
distal radius fractures, external fixators are now more frequently used.
PMID- 9648480
TI - [Physical training].
AB - Physical training repairs bone structures and increases bone mass as well as the
most effective medicine, through inducing piezo-electric potential and
stimulating osteoblastic activity. Although gain of bone mass depends on duration
and intensity of mechanical loading, researches have shown that daily 30 minutes'
mild training such as walking has positive effect on increasing bone mass, even
in elderly persons. Compared with calcium intakes or sun exposure, habits related
to bone metabolism, physical activity is significantly greater to increase bone
mass. Interestingly, it is apparent in our study that habitual stroll walks of
older age groups prevent the falls which is another risk of their fracture in the
extremities.
PMID- 9648481
TI - [Nutritional therapy].
AB - Osteoporosis is one of the life style related diseases. Therefore, from the
viewpoint of prevention, daily diet and nutrient intake are important. An
adequate intake of calcium together with nutrient balance plays an essential role
in maintaining and promoting health and preventing osteoporosis. Moreover, prior
to nutritional therapy, it is essential to understand the current nutritional
status and dietary habits of the individual.
PMID- 9648482
TI - [Epidemiology of osteoporosis: incidence, prevalence, and prognosis].
AB - Though the exact and cumulative incidence of osteoporosis has not been examined,
using the criteria that osteoporosis is defined by a decrease of bone mineral
density (BMD) below 70% from young adult mean (YAM), the prevalence of
osteoporosis among the Japanese women can be estimated as to be more than either
30% (by spinal BMD) or 37% (by femoral BMD) in 60's, 37% or 64% in 70's, and 42%
or 90% in 80's, respectively. The total number of osteoporosis among the women
with age 50 and over can be also estimated as to be either about 5 million (by
spinal BMD) or 8.5 million (by forearm BMD). National survey shows that the ratio
of people receiving treatment for osteoporosis is 34.5 per 1,000 among the
elderly with age 65 and over. In addition, both functional transition and
survival rate of discharged patients with osteoporotic hip fracture are discussed
as prognosis of osteoporosis.
PMID- 9648483
TI - [Epidemiology--risk factors and preventive strategy].
AB - Many factors, including age, sex, menopause, genetic makeup, calcium intake, and
physical exercise, influence the development of osteoporosis. Bone density is a
major risk factor for fracture at spine and hip. However, risk of hip fracture is
affected by factors not limited to bone strength, for example, factors related to
falling. These risk factors can be classified as those that are controllable and
those that are not. Although one has uncontrollable risk factors, the risk of hip
fracture can be decreased by reducing the controllable risk factors. To prevent
osteoporosis and fracture, it is necessary to be familiar with an individual's
risk factors and offer guidance to reduce the controllable risks. Maintaining or
increasing bone mass are essential for those with uncontrollable factors.
PMID- 9648484
TI - [Glucocorticoid-induced osteoporosis--mechanisms and preventions].
AB - It has been well known that patients with Cushing's syndrome have frequently
osteoporosis or bone loss due to excess endogenous glucocorticoids and also
osteopenia or osteoporosis is commonly observed in patients with long-term
glucocorticoid therapy. In this paper, the mechanisms involved in bone loss in
Cushing's syndrome and glucocorticoid-induced osteoporosis were demonstrated. In
the patients with Cushing's syndrome, excess endogenous glucocorticoids increase
bone resorption and decrease bone formation and also act to depress intestinal
calcium absorption and increase urinary calcium excretion, leading to
compensatory stimulation of parathyroid hormone secretion. Then, parathyroid
hormone stimulates bone resorption. Thus, secondary osteoporosis is commonly
observed due to excess glucocorticoid. Finally, preventions and managements for
glucocorticoid-induced osteoporosis were discussed.
PMID- 9648485
TI - [Secondary osteoporosis and its treatment--diabetes mellitus].
AB - Japanese epidemiological study showed higher frequency of osteopenia/osteoporosis
in diabetic patients as compared with sex- and age-matched control. The mechanism
by which bone loss occurs in diabetic patients could be explained by a reduction
of insulin/insulin-like growth factor-I action, sustained hyperglycemic state, a
generation of advanced glycosylation end-products, and diabetic complication such
as neuropathy, nephropathy and myopathy. Osteoblast deficit is hypothesized to
play a major role in the occurrence of diabetic osteopenia. Besides the
deficiency of insulin and insulin-like growth factor-I, we demonstrated that
sustained hyperglycemia alone causes suppression of osteoblast proliferation and
its response to parathyroid hormone and 1 alpha, 25-dihydroxyvitamin D,
Hyporesponse of osteoblast to 1 alpha, 25-dihydroxyvitamin D, was also confirmed
in diabetic patients as reflected by a reduction in an incremental response of
serum osteocalcin during 1 alpha, 25-dihydroxyvitamin D administration. The
regimens having stimulatory effect on bone turnover, such as intermittent PTH
therapy and vitamin D, are recommended to treat diabetic osteopenia, besides
improvement of diabetic control state.
PMID- 9648486
TI - [Bone changes in thyrotoxicosis].
AB - Thyroid hormone (T3) is essential for normal bone growth and bone metabolism. T3
stimulates bone formation directly through T3 receptors in osteoblasts. T3 also
stimulates bone resorption by osteoclasts probably secondary through osteoblasts.
In thyrotoxicosis accelerated bone formation and resorption resulted in high turn
over bone loss. Bone metabolic markers elevate reflecting thyrotoxic state.
Normalizing thyroid hormone level at least partially restore bone mineral
content. In patients under thyroid hormone replacement therapy or TSH suppression
therapy TSH and free thyroid hormones should be monitored to prevent unnecessary
bone loss. Especially in postmenopausal women with thyrotoxicosis or thyroid
hormone therapy the assessment of bone mineral content is required.
PMID- 9648487
TI - [Hyperparathyroidism and its management].
AB - Hyperparathyroidism (HPT), resulting from the excess of endogenous parathyroid
hormone is cited as one of diseases which cause secondary osteoporosis. HPT
consists of primary (1 degree) and secondary (2 degrees) HPT, resulting mainly
from chronic renal failure (CRF). HPT is easily distingishable from primary
osteoporosis by biochemical measurements. Parathyroidectomy (PTX) is the only
option available for the radical cure of 1 degree HPT and more than 10% increase
in bone mass occurs after PTX. On the other hand, dietary phosphorus restriction,
phosphorus binders, active vitamin D3 metabolites are useful for 2 degrees HPT
due to CRF. When these treatments are not effective to inhibit PTH secretion
adequately, oral active vitamin D3 pulse therapy, PTX and percutaneous ethanol
injection therapy should be considered.
PMID- 9648488
TI - [Osteoporosis in rheumatoid arthritis].
AB - Patients with rheumatoid arthritis (RA) develop both periarticular and
generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs
early in the course of RA and is one of the earliest radiological signs of RA. An
uncoupled state in bone resorption-formation linkage, contributes to the
development of periarticular osteopenia and it might be mediated through an
increased productions of cytokines and prostaglandins by synovium and bone
marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for
the prevention of periarticular osteopenia. Generalized osteoporosis is also
common in RA and leads to increased risk of fractures. Generalized osteoporosis
considered to be multifactorial and factors contributing to lumbar osteoporosis
might be different from those to loss of appendicular bones, such as femur and
radius. Corticosteroids and menopausal state are important risk factors for
lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also
important determinants. According to the previous studies, however, the influence
of functional impairment is more prominent in the femoral BMD compared to spinal
BMD. In addition to control of RA and maintenance of physical activity, hormone
replacement therapy (HRT) and bisphosphonate are possible agents for the
treatment of osteoporosis in RA patients, especially postmenopausal women.
PMID- 9648489
TI - [Hepatic osteodystrophy].
AB - Bone thinning causing both fractures and severe pain not associated with
fractures has been recognized in patients with chronic liver diseases. The
patients most commonly affected are those with primary or secondary biliary
cirrhosis, but those with alcoholic liver disease and cirrhosis after active
chronic hepatitis may also be involved. Chronic liver disease has also been
recognized as an important cause of osteoporosis in both sexes, with the
mechanism thought to be a combination of calcium and/or vitamin D. The 9.1%
patients with chronic active hepatitis accompanied with osteodystrophy. But 50%
cirrhotic patients accompanied with osteodystrophy. Bone densitometry was
determined by Digital Image Processing Method (Osteodystrophy < mean-2SD: age-
and sex-matched normal value). Serum levels of osteocalcin (BGP) and parathyroid
hormone (PTH) in patients of hepatic cirrhosis without osteodystrophy were lower
than those with osteodystrophy. These results were suggested that hepatic
osteodystrophy was rapidly turnover osteodystrophy. To function physiologically,
vitamin D must be hydroxylation in liver to 25-(OH)-D and subsequently by the
kidney to 1 alfa, 25-(OH)2-D. Osteodystrophy associated with hepatic cirrhosis is
due to a defect in the 1 alfa-hydroxylation by the kidney rather than a hepatic
hydroxylation defect. 1 alfa OH-D3 is very useful for treatment for hepatic
osteodystrophy.
PMID- 9648490
TI - [Secondary osteoporosis in gynecology].
AB - Several diseases and medications are known to induce secondary osteoporosis.
Among them, same situations are related to gynecological field. They include
Turner's syndrome, anorexia nervosa, ovarian dysfunction, oophorectomy, GnRH
agonist therapy, and osteoporosis associated with pregnancy. We briefly describe
these secondary osteoporosis in this article as follows. Several studies have
found osteoporosis to be a common complication of Turner's syndrome and hormone
replacement therapy has been used as a possible management; in anorexic patient,
low body weight, prolonged amenorrhea, early onset of anorexia nervosa, and
hypercortisolism have been reported to be risks for bone demineralization; since
oophorectomy which is a common intervention in gynecology leads osteoporosis, it
is important to prevent osteoporosis caused by surgery as well as postmenopausal
osteoporosis; GnRH agonist, which induces estrogen deficient state and affect
bone mass, is commonly used as a management for endometriosis and leiomyoma of
uterus; associated with pregnancy, post-pregnancy spinal osteoporosis and
transient osteoporosis of the hip are clinically considered to be important and
heparin therapy and magnesium sulfate therapy are commonly employed during
pregnancy, affecting calcium homeostasis.
PMID- 9648491
TI - [Hypogonadism and osteoporosis].
AB - Hypogonadism, whether caused by primary gonadal failure or secondary gonadotropin
deficiency, is associated with osteoporosis. Even gonadotropin-releasing hormone
therapy for endometriosis causes a decrease in bone mineral density by reducing
serum estradiol level. Recent interesting studies of a male patient with a
nonsense mutation in the estrogen receptor gene, a girl with missense mutation in
the aromatase gene, and knock-out mice targeting estrogen receptor gene suggest
that estrogen is very important to maintain normal bone density even in a male.
Androgen deficiency increase risk for osteoporosis, but estrogen may compensate
for it, since osteoporosis is not remarkable in patients with androgen
resistance. Growth hormone deficiency and hyperprolactinemia are also related to
gonadal function and thus bone metabolism.
PMID- 9648492
TI - [Dysregulation of mucosal immunity and inflammatory bowel diseases].
AB - Normal mucosal immunity is regulated in a delicate balance between up- and down
regulatory responses to dietal or bacterial antigens. Recent studies demonstrated
that pathogenesis of inflammatory bowel disease could be dysregulation of the
balance of mucosal immunity. Recent advances in animal models of inflammatory
bowel disease, pathogenic roles of mucosal immunoregulatory T cells, cytokines
and intestinal flora are reviewed.
PMID- 9648493
TI - [The control of brain tissue temperature and stimulation of dopamine-immune
system to the severe brain injury patients].
AB - The recovery of injured neurons in primely brain damage, neuroprotection to the
secondary brain damage (such as brain edema, brain ischemia, free radicals,
neuroexcitation and ICP elevation), activation of gene-tropic regeneration, and
prevention of apobiosis are major targets on the management of severe brain
injury. However, excess release of catecholamines (catecholamine surge) make a
very difficult to control of cerebral hypoxia by changes of systemic blood
circulations. Mild cerebral hypothermia is only one method to prevent of these
catecholamines surge. We developed new technique, cerebral hypothermia that
control brain tissue temperature at 32-34 degrees C with more than 800 ml/min.
oxygen delivery at acute stage. Combination therapy with these cerebral
hypothermia and replacement of cerebral dopamine-pituitary hormone-estrogen was
very successful to prevent of vegetation after severe brain injury.
PMID- 9648494
TI - [The 40th annual meeting of the Japanese Society of Child Neurology. June 4-6,
1998. Yokohama, Japan. Abstracts].
PMID- 9648495
TI - [Montelukast--a new building block in the therapy of bronchial asthma.
Introductory Symposium, MSD Sharp & Dohme GMBH. Telfs (Austria) 6-8 March 1998].
PMID- 9648496
TI - [New perspectives in the treatment of bronchial cancer. Pan-European Lung Cancer
Forum: "New perspectives on the Management of Lung Cancer". Sitges/Barcelona, 14
March 1998].
PMID- 9648497
TI - Dengue.
PMID- 9648498
TI - WHO meeting on maternal and neonatal pneumococcal immunization.
PMID- 9648499
TI - Global leprosy distribution in 1998.
PMID- 9648500
TI - Overview of evolutionary aspects of omega 3 fatty acids in the diet.
PMID- 9648501
TI - Dietary intake of long-chain polyunsaturated fatty acids during the paleolithic.
PMID- 9648502
TI - Omega 3 fatty acids and cardiovascular disease.
PMID- 9648503
TI - Regulatory effects of polyunsaturates on bone modeling and cartilage function.
PMID- 9648504
TI - Omega 3 fatty acid status in patients with retinitis pigmentosa.
PMID- 9648505
TI - Production of docosahexaenoic acid from microalgae and its benefits for use in
animal feeds.
PMID- 9648506
TI - Production of docosahexaenoic acid-enriched poultry eggs and meat using an algae
based feed ingredient.
PMID- 9648507
TI - Designer eggs and their nutritional and functional significance.
PMID- 9648508
TI - Poultry-based alternatives for enhancing the omega 3 fatty acid content of
American diets.
PMID- 9648509
TI - Single cell oil sources of docosahexaenoic acid: clinical studies.
PMID- 9648510
TI - Omega 3-enriched pork.
PMID- 9648511
TI - Enrichment of beef with omega 3 fatty acids.
PMID- 9648512
TI - Docosahexaenoic acid-enriched milk.
PMID- 9648513
TI - Omega 3 products: from research to retail.
PMID- 9648514
TI - Utilization of omega 3 fatty acids in companion animal nutrition.
PMID- 9648515
TI - Metabolism of alpha-linolenic acid from flaxseed in dogs.
PMID- 9648516
TI - Global food fortification perspectives of long-chain omega 3 fatty acids.
PMID- 9648517
TI - Regulatory aspects of omega 3 fatty acid labelling in Canada.
PMID- 9648518
TI - Omega 3 fatty acids--an Australian perspective.
PMID- 9648519
TI - Redefining dietary reference values and food safety.
PMID- 9648520
TI - The cytotoxicity of 2-formyl and 2-acetyl-(6-picolyl)-4N-substituted
thiosemicarbazones and their copper(II) complexes.
AB - 2-Acetyl-(6-picolyl)-4N-substituted thiosemicarbazones and their copper(II)
complexes were shown to be potent antineoplastic and cytotoxic agents against
murine and human cultured cells. Numerous derivatives were as active against
solid tumor growth as clinically useful agents. The agents inhibited L1210 DNA
and RNA syntheses with inhibition of key regulatory enzyme activities of the
purine pathway as well as nucleoside kinase activities. d[NTP] pools were reduced
and DNA strand scission occurred. These agents were DNA topoisomerase II
inhibitors with lower IC50 values than that of VP-16. However, they did not cause
L1210 DNA protein linked breaks and actually protected against those breaks
afforded by VP-16. The agents were not synergistic with VP-16 in reducing cell
growth or DNA synthesis although they did reduce growth of L1210 cells in agar
suspended media.
PMID- 9648521
TI - Controlled insulin release from chitosan microparticles.
AB - This study deals with the production of chitosan microparticles containing
insulin by interfacial crosslinkage of chitosan solubilized in the aqueous phase
of a water/oil dispersion in the presence of ascorbyl palmitate. The use of
ascorbyl palmitate as interfacial crosslinker is based on its amphiphilic
properties allowing its disposition at the water/oil interface of the preparative
dispersion, thus permitting covalent bond formation with the amino groups of
chitosan when its oxidation to dehydroascorbyl palmitate takes place during
microparticle preparation. This preparation method produced microparticles
characterized by high loading levels of insulin, completely releasing the drug in
about 80 h at an almost constant release rate as determined by spectrophotometric
and spectrofluorimetric methods. In contrast, the replacement of ascorbyl
palmitate by dehydroascorbyl palmitate provided microparticles incompletely
releasing the incorporated drug and characterized by a non-constant release rate
over time due to the higher lipophilicity of dehydroascorbyl palmitate which
hinders its disposition at the water/oil interface and thus decreases the
crosslinking efficiency and increases the lipophilicity of the microparticle
surface. The efficiency of the spectrofluorimetric and spectrophotometric methods
used for determination of the stability and release of the insulin from the
chitosan microparticles is also discussed.
PMID- 9648522
TI - Synthesis and antibacterial activities of new carbapenems having a proline
reverse amide moiety at the C-2 position.
AB - The synthesis of new 1 beta-methylcarbapenems (1a-l) having a proline reverse
amide moiety at the C-2 position and their in vitro antibacterial activities are
described. The compounds were evaluated by the Mueller-Hinton agar dilution
method and compared with meropenem as control. Aliphatic amides (1a-h) are found
to show greater antibacterial activity than aromatic amides (1i-l). Moreover, C-2
free amino compound (1m) reveals greater activity than any other amide compounds
(1a-l).
PMID- 9648523
TI - 7-Aminocoumarins are substrates of cytochrome P450-isozymes.
AB - N-Alkyl-7-aminocoumarins are dealkylated by murine cytochrome P450. There are
differences between the N-dealkylation of secondary and tertiary amines. 7
Ethylamino-4-methylcoumarin is deethylated by isozymes induced by 3
methylcholanthrene, in contrast to 7-diethylamino-4-methylcoumarin and 7-diethyl
amino-4-trifluoromethylcoumarin, which are deethylated mostly by isozymes induced
by phenobarbital. Although the deethylation of the secondary amine can be
increased also by a pretreatment with pyrazole, a specific inducer of the
coumarin 7-hydroxylase (CYP2A5), there is no specific affinity for this isozyme.
This result is supported by the second specific inducer of CYP2A5 cobalt, because
cobalt did not influence the deethylation of 7-ethylamino-4-methylcoumarin. In
addition, it was shown that (in contrast to earlier investigations) pyrazole
beside CYP2A5 also induces further cytochrome P450 isozymes. In series of four
compounds, 7-ethylamino-4-methylcoumarin is the singular 7-aminocoumarin which is
accepted as substrate by the coumarin 7-hydroxylase. In addition, the metabolism
of the 7-aminocoumarins was investigated to look for further metabolic products.
The most interesting result is the double deethylation of 7-diethylamino-4
methylcoumarin to the primary amine. In the scope of the studies the advantages
of new calculating structure-activity-relationships (QSAR-plot) could also be
demonstrated.
PMID- 9648524
TI - More than suggestion: the effect of interviewing techniques from the McMartin
Preschool case.
AB - Child interviewing techniques derived from transcripts of the McMartin Preschool
case were found to be substantially more effective than simple suggestive
questions at inducing preschool children to make false allegations against a
classroom visitor. Thirty-six children interviewed with McMartin techniques made
58% accusations, compared with 17% for 30 children interviewed with suggestive
questions. Social influence and reinforcement appeared to be more powerful
determinants of children's answers than simple suggestive questions. The SIRR
model is proposed to explain how false statements may be elicited from children
or adults. Categories identified in the SIRR model are suggestive questions,
social influence, reinforcement, and removal from direct experience.
PMID- 9648525
TI - Understanding pretest and posttest reactions to cognitive ability and personality
tests.
AB - To understand the nature of test reactions and their relationship to test
performance, the relationships among belief in tests, pretest reactions, test
performance, and posttest reactions were modeled for cognitive ability and
personality tests. Results from structural equation models that were fitted to
responses from 197 undergraduate examinees supported the hypothesized
relationships. On the cognitive ability test, pretest reactions affected test
performance and mediated the relationship between belief in tests and test
performance. Test performance affected posttest reactions even after taking into
account the effect of pretest reactions. On the personality test, belief in tests
affected pretest and posttest reactions, but the three variables were unrelated
to test performance (Conscientiousness scores). Conceptual, methodological, and
practical implications of the findings are discussed in the context of research
on test reactions and test performance.
PMID- 9648526
TI - Emotional exhaustion as a predictor of job performance and voluntary turnover.
AB - Recent research suggests that a better understanding of emotional exhaustion
requires the development of new theoretical perspectives. To that end, with the
conservation of resources model (COR) as the theoretical framework, the present 1
year longitudinal study was undertaken. Composed of 52 social welfare workers,
this research examined the relationship of emotional exhaustion to job
satisfaction, voluntary turnover, and job performance. Positive affectivity (PA)
and negative affectivity (NA) were used as control variables. Whereas emotional
exhaustion was unrelated to job satisfaction, it was associated with both
performance and subsequent turnover. In addition, the relationship between
emotional exhaustion and performance and also between emotional exhaustion and
turnover remained significant above and beyond the effects of PA and NA. Future
research directions and implications of the findings are introduced.
PMID- 9648527
TI - Singlet oxygen- versus nonsinglet oxygen-mediated mechanisms of sensitizer
photobleaching and their effects on photodynamic dosimetry.
AB - We report the effects of singlet oxygen (1O2) and non-1O2-mediated sensitizer
photobleaching on oxygen consumption and dosimetry during photodynamic therapy
(PDT) of sensitized multicell tumor spheroids. We develop a theoretical model for
the description of non-1O2-mediated photobleaching resulting from irreversible
reactions of the excited singlet or triplet sensitizer populations with cell
substrate. We show that the fluence-dependent simple exponential decay expression
of sensitizer degradation is not consistent with these mechanisms and, therefore,
with any reasonable mechanism that we consider, because we have shown previously
that 1O2-mediated photobleaching cannot be described by a simple exponential with
a constant photobleaching coefficient (I. Georgakoudi et al., Photochem.
Photobiol. 65, 135-144, 1997). Analysis of oxygen microelectrode measurements
performed at the edge of Nile blue selenium (EtNBSe)- and protoporphyrin IX
(PpIX)-sensitized spheroids during PDT demonstrates that the former drug
photobleaches via a non-1O2-mediated mechanism, while the latter is degraded via
a 1O2-mediated mechanism. Comparisons of the cytotoxic effects of EtNBSe with
those of Photofrin (a drug that is degraded via a 1O2-mediated mechanism)
indicate that the lower threshold 1O2 dose and the higher extinction coefficient
and 1O2 yield for EtNBSe do not necessarily result in improved photodynamic
effects, thus emphasizing the importance of the sensitizer photobleaching
mechanism for dosimetry.
PMID- 9648528
TI - Novel visible and ultraviolet light photogeneration of hydroxyl radicals by 2
methyl-4-nitro-quinoline-N-oxide (MNO) and 4,4'-dinitro-(2,2')bipyridinyl-N,N'
dioxide (DBD).
AB - Chemicals that upon absorption of light generate hydroxyl radicals (.OH), free of
other damaging species under physiological conditions, are useful tools for the
study of the biological effects of .OH radical and for its utilization for
analytical purposes. We report the novel property of 2-methyl-4-nitro-quinoline-N
oxide (MNO) and 4,4'-dinitro-(2,2')bipyridinyl-N,N'-dioxide (DBD) to act as
photogenerators of .OH with UV and visible light. Upon irradiation with 360-400
nm light MNO and DBD generate free radicals that convert coumarin carboxylic acid
(CCA) to fluorescent 7-OH-CCA; the .OH radical scavengers dimethylsulfoxide
(DMSO) and ethanol eliminate the induction of 7-OH-CCA fluorescence. Upon 400 nm
illumination in the presence of MNO, supercoiled plasmid DNA is converted to
circular and strand breakage is significantly reduced in the presence of DMSO and
completely absent in the absence of MNO. The conversion of CCA to 7-OH-CCA and of
supercoiled plasmid to circular DNA are also observed in the absence of oxygen.
Taken together, these data indicate that MNO and DBD constitute novel .OH
generating compounds. Because currently known .OH-photogenerating compounds
require UV illumination (< 360 nm) that also damages DNA and cells directly, the
property of MNO to generate .OH upon 400 nm illumination is advantageous when
studies on cells, DNA and other biomolecules are conducted.
PMID- 9648529
TI - Fluorescence anisotropy controlled by light quenching.
AB - We demonstrated that fluorescence anisotropy can be effectively decreased or
increased in the presence of light quenching, depending on relative polarizations
of excitation and quenching pulses. For parallel light quenching, anisotropy
decreases to 0.103 and z-axis symmetry is preserved. In the presence of
perpendicular light quenching, the steady-state anisotropy of a pyridine-2
glycerol solution increases from 0.368 for an unquenched sample to 0.484 for a
quenched one. We show that the angular distribution of transition moments loses z
axis symmetry in the presence of perpendicular light quenching. In these cases we
used more general definitions of anisotropy. Induced by light quenching,
anisotropy can be applied in both steady-state and time-resolved measurements. In
particular, the systems with low or no anisotropy can be investigated with the
proposed technique.
PMID- 9648530
TI - Assessment of DNA damage induced by broadband and narrowband UVB in cultured
lymphoblasts and keratinocytes using the comet assay.
AB - Phototherapy with broadband UVB is an effective treatment for inflammatory
dermatoses. A newly developed fluorescent UVB lamp (Philips TL01) that emits a
narrowband UVB around 311 nm was shown to be superior for the phototherapy of
psoriasis. In order to contribute to the knowledge about the carcinogenic
potential of this UVB source, we measured the DNA damage in lymphoblasts and
keratinocytes induced by narrowband UVB and compared it with that by conventional
broadband UVB using the single cell gel electrophoresis (comet assay). At equal
doses, broadband UVB produced more DNA damage than narrowband UVB. However, in
phototherapy of psoriasis, up to 10-fold higher doses are used with TL01. When
therapeutically equivalent doses were compared (10-fold correction for narrowband
UVB), we found only slight differences in the amount of DNA damage produced by
broadband and narrowband UVB. This supports the already existing evidence that
for phototherapy narrowband UVB is not more carcinogenic than broadband UVB.
PMID- 9648531
TI - Protection against UV-induced reactive intermediates in human cells and mouse
skin by glutathione precursors: a comparison of N-acetylcysteine and glutathione
ethylester.
AB - Because glutathione (GSH) plays a central part in the endogenous defense against
UV radiation, an increase in GSH might provide photoprotection. Two agents that
increase GSH levels were investigated. Cultured human cells and mouse skin were
treated with N-acetylcysteine (NAC) and glutathione ethylester (GSH-Et). After 30
min, the GSH level was determined by HPLC. Photoprotection was assessed by
testing the ability of the thiols to scavenge UV-induced reactive intermediates
in the same models. As compared to control cells, NAC and GSH-Et increased
intracellular GSH in vitro to maximally 144% and 174% respectively. In vitro
protection (maximum 23% for NAC and 21% for GSH-Et) did not correlate to the
intracellular GSH level but to the concentration of the thiols in the medium. In
vivo, epidermal GSH was increased to maximally 163% of the control level by NAC
and 1234% by GSH-Et. The maximum in vivo photoprotection provided by GSH-Et was
55%, similar to what was found previously for NAC. Again, the protection seemed
more closely correlated to the thiol dose than to the GSH level. The study showed
that the protection against UV-induced reactive intermediates depends on a
general antioxidant action of these thiols, rather than only on their role as GSH
precursors.
PMID- 9648532
TI - Inhibitory effects of plant tannins on ultraviolet light-induced epidermal DNA
synthesis in hairless mice.
AB - Naturally occurring hydrolyzable (HT) and condensed (CT) tannins and their
monomeric units were tested for their ability to inhibit the stimulation of DNA
synthesis by UVB radiation. Hairless mice were irradiated with either single (200
mJ/cm2) or multiple (150 mJ/cm2) doses of UVB applied at 24 h intervals and
epidermal DNA synthesis was measured at different times after the last of these
treatments. The peak of DNA synthesis that is observed 48-56 h after a single UVB
irradiation shifts to an earlier time of 16-24 h after multiple UVB treatments.
Interestingly, the early inhibitory period of DNA synthesis observed 8 h after a
single UVB treatment is not detected following multiple UVB treatments. Rather,
DNA synthesis is stimulated six-fold 24 h after multiple UVB treatment, a
response that is higher than the peak occurring 48-56 h after a single UVB
irradiation. The disappearance of the early period of inhibition when the peak of
DNA synthesis shifts to an earlier time may be linked to reactive oxygen species
brought to the epidermis by infiltrating leukocytes, which, in turn, act as
second messengers to stimulate growth signals in cells. Topical applications of
HT or CT remarkably inhibit the DNA responses to single and multiple UVB
treatments, an effect that is dependent on the dose and time of administration.
Indeed, the peak stimulation of DNA synthesis is maximally inhibited when 17 mg
of Tarapod tannic acid (TA), an HT, are applied topically 20 min before a single
UVB treatment. The polymeric tannins inhibited DNA synthesis to a greater degree
than equal doses of their monomeric units, gallic acid and catechin. These
results suggest that various oligomeric HT and CT may be useful against tumor
promoting responses associated with the exposure of skin to physical carcinogens.
PMID- 9648533
TI - Postadministration protective effect of magnesium-L-ascorbyl-phosphate on the
development of UVB-induced cutaneous damage in mice.
AB - The effects of stable vitamin C, magnesium-L-ascorbyl-2-phosphate (MAP),
administered after acute and chronic exposure to UVB irradiation were
investigated using hairless mice. Intraperitoneal administration of 100 mg/kg of
MAP immediately after acute exposure to 15 kJ/m2 of UVB significantly prevented
increases of UVB-induced lipid peroxidation in skin and sialic acid in serum, an
inflammation marker. Administration of 50 mg/kg of MAP immediately after each
exposure significantly delayed skin tumor formation and hyperplasia induced by
chronic exposure to 2 kJ/m2 of UVB. Intraperitoneal administration of 200 mg/kg
of MAP produced an increase in ascorbic acid (As) levels in the serum, liver and
skin within 15 min. Serum As levels quickly returned to normal, but hepatic and
cutaneous levels remained elevated before returning to normal after 24 h,
suggesting that MAP was converted to As in the serum and in those tissues.
Ultraviolet B-induced hydroxyl radical generation in murine skin homogenates was
scavenged by As-Na addition, which was directly detected by electron spin
resonance (ESR). These results suggest that postadministration of MAP delays
progression of skin damage induced by UVB irradiation. It is presumed that MAP,
once converted to As, exhibits such inhibitory effects by scavenging hydroxyl and
lipid radicals generated as a direct or indirect result of UVB exposure.
PMID- 9648534
TI - The general kinetic model of electron transfer in photosynthetic reaction centers
activated by multiple flashes.
AB - A new general kinetic model for the functioning of photosynthetic reaction
centers (RC) of purple bacteria, under multiple flash activation, has been
developed. The model includes the primary electron donor (P870) as well as the
primary (QA) and secondary (QB) acceptor quinones. The new features of this
general model include: (1) consideration of four different states of the QB
binding site (vacant, occupied by QB, by QB- and by QBH2), (2) incorporation of
the dark relaxation of the RC between flashes, (3) the assumption of fast
exchange of quinones between the RC and quinone pool in detergent micelles or
chromatophore membrane, (4) description of the kinetics of electron transfer in
both oxidized (no donor for P870+) and reduced (in the presence of donor for
P870+) conditions simultaneously, (5) the consideration of both single and
multiple flash activation of the RC of purple bacteria and (6) consideration of
the cumulative effects of all previous flashes of the series in the response
induced by the current flash. This model is used to calculate and predict (1)
flash-induced binary oscillations of the secondary acceptor semiquinone (QB-),
(2) flash-induced behavior of P870+ in the presence and absence of electron donor
and (3) the apparent equilibrium constant of electron transfer between QA and QB
and others. Different characteristics of RC are analyzed as a function of flash
intensity, time between flashes, concentration of electron donor, redox-potential
of the medium, concentration of pool quinone and quinol, association and
dissociation equilibrium constants for quinone and quinol at the QB binding site,
equilibrium constants of electron transfer between QA- and QB and between QA- and
QB-, as well as the rate constants of oxidation of QA- and QB- by redox
mediators. The proposed model can be used as a basis for assays of kinetic
behavior of native and mutant RC of purple bacteria and for determination of the
factors influencing the release of QH2 from RC. The latter is needed for analysis
of factors controlling light-activated electron transport in the cytochrome bc1
complexes of purple bacteria by quinol molecules released from RC. The developed
general approach for parallel consideration of flash-induced transitions of RC
and its following dark relaxation between flashes can also be used for kinetic
description of photosynthetic RC of oxygenic photosynthesis.
PMID- 9648535
TI - Duck hepatitis B virus inactivation and 8-methoxypsoralen photoadduct formation
in human platelet concentrates.
AB - Photochemical inactivation (PCI) of virus and bacteria in platelet concentrates
(PC) has been demonstrated using 8-methoxypsoralen (8-MOP) and long-wavelength UV
light (UVA). To study inactivation of blood-borne virus, we have employed duck
hepatitis B virus (DHBV), a model for human hepatitis B virus. A specific
hepatocyte culture infectivity assay, with PCR detection, could measure 5-6 log10
virus kill. The DHBV inactivation in PC was dependent on UVA dose, was enhanced
when plasma was reduced from 100% to 20% and was limited by 8-MOP solubility in
the reduced-plasma medium. Optimum conditions for PCI were 100 micrograms/mL 8
MOP in 20% plasma and 80% synthetic platelet storage medium. A radiolabeling
assay for 8-MOP photoadducts in hepatocytes seeded into PC confirmed that DHBV
inactivation reflected DNA modification and indicated that adduct formation was
insensitive to minor variations in conditions. Kinetic modeling indicated that
optimum adduct formation was a compromise between 8-MOP dark binding and optical
transmittance and that plasma proteins competed for 8-MOP binding. The PCI
results in various media correlated with corresponding DNA modification densities
and were compared to statistical models incorporating DHBV characteristics and
predictions of 8-MOP crosslink formation between DNA strands. Behavior was
consistent with one or a small number of lethal modifications per DNA strand,
including monoadducts, but probably not crosslinks alone. A minor subpopulation
of DHBV was found to be somewhat more difficult to inactivate, consistent with
three-fold lower modification, due possibly to single-stranded DNA character or
host repair of photoadducts.
PMID- 9648536
TI - Susceptibility to effects of UVB irradiation on induction of contact sensitivity,
relevance of number and function of Langerhans cells and epidermal macrophages.
AB - Sensitization on skin exposed to acute low-dose UVB irradiation separates normal
humans into two phenotypically distinct groups: One group, following
sensitization on UVB-irradiated skin, develops contact sensitivity, designated
UVB resistant (UVB-R) and the second group, following sensitization on UVB
irradiated skin, fails to develop contact sensitivity, designated UVB susceptible
(UVB-S). To investigate whether UVB susceptibility in humans in related to
antigen-presenting activity in the skin we studied the effect of UVB irradiation
on the number and function of the epidermal antigen-presenting cells in
volunteers identified as UVB-R and UVB-S. Single cell suspensions of epidermal
cells from control skin and skin exposed to 3 minimal erythema doses (MED) of UVB
3 days previously were stained for Langerhans cells (CD1a+HLA-DR+) and epidermal
macrophages (CD1a-HLA-DR+). The UVB exposure of the skin significantly decreased
the percentage of Langerhans cells (UVB-R: n = 7, P < 0.02, UVB-S: n = 6, P <
0.03) and increased the percentage of epidermal macrophages (UVB-R: n = 7, P <
0.03, UVB-S: n = 6, P < 0.03) however to the same degree in both the UVB-R and
the UVB-S group. To study the effect on Langerhans cell alloreactivity, epidermal
cells were harvested immediately after UVB irradiation. However, in both UVB-R
and UVB-S subjects the Langerhans cell alloreactivity was blocked to the same
degree immediately after UVB irradiation compared to nonirradiated epidermal
cells. To determine the effect of UVB irradiation on epidermal macrophages,
epidermal cells were harvested 3 days after UVB irradiation. Irradiated epidermal
cells from both UVB-R and UVB-S subjects demonstrated a strong antigen-presenting
capacity compared to epidermal cells from control skin leading to activation of T
cells that mainly secrete interferon (IFN)-gamma and not interleukin (IL)-4. In
conclusion we found that UVB susceptibility was not correlated with the number of
Langerhans cells or epidermal macrophages in the skin at the same time of
sensitization. Neither was it correlated with the capacity of Langerhans cells
nor UVB-induced epidermal macrophages to activate T cells in vitro.
PMID- 9648537
TI - Variation in photodynamic efficacy during the cellular uptake of two
phthalocyanine photosensitizers.
AB - A decrease in the efficacy of photodynamic therapy (PDT) with phthalocyanine
photosensitizers was observed for lymphoblastic murine and human cell lines as
the time between the addition of the photosensitizer, aluminum phthalocyanine
(AIPc), to the culture medium and exposure to light was increased from 4 h to 18
h. The total intracellular concentration of photosensitizer did not decrease
significantly during this 18 h interval. For the murine cell lines, the maximum
cytotoxic and mutagenic effects were observed when the time between addition of
the photosensitizer and irradiation was between 1 and 4 h. The time course of the
variations in efficacy did not vary greatly from one murine cell line to another,
even though the cell lines differ markedly in the extent of their cytotoxic and
mutagenic response. The time course of the variation was similar for cytotoxicity
and mutagenicity, as well as for the induction of DNA fragmentation. The human
lymphoblastic cell line, WTK1, showed less variation in survival and mutability
with time than did the murine cell lines. With Pc 4
(HOSiPcOSi[CH3]2[CH2]3N[CH3]2) as the photosensitizer, the photocytotoxicity for
murine L5178Y (LY)-S1 cells did not change significantly as the time between
addition of Pc 4 and irradiation was increased from 2 to 18 h. However, the
mutagenicity decreased by a factor of three during this interval. The
mutagenicity of PDT with Pc 4 was much less in LY-S1 cells than that with AlPc.
The results suggest that the variation in the efficacy observed for AlPc-induced
photocytotoxicity is caused by changes in the intracellular distribution and/or
the aggregation of the photosensitizer with time after its addition.
PMID- 9648538
TI - Effect of membrane potential on the binding of merocyanine 540 to human
erythrocytes.
AB - Illumination of erythrocytes in the presence of merocyanine 540 (MC540) resulted
in changed binding characteristics of MC540, i.e. a red shift in the emission
maximum of bound dye with an increase in the relative fluorescence quantum yield.
Aluminum phthalocyanine tetrasulfonate-mediated photodynamic treatment, before
addition of MC540, resulted in a comparable change in the MC540-binding
characteristics with, in addition, an increase in the concentration of MC540 in
the membrane. Both photodynamic treatments induce depolarization of the red cell
membrane, with a dose dependency comparable to that of changed MC540 binding.
Also depolarization, induced by incubation of the cells with A23187 in the
presence of Ca2+ in high [K+] buffer, resulted in similar changes in the MC540
binding characteristics. These results indicate a relation between
photodynamically induced membrane depolarization and changed MC540-binding
characteristics. Hyperpolarization induced by incubation with A23187 in low [K+]
buffer resulted in decreased binding of MC540. In accordance, the MC540-mediated
photodamage to red cells decreased upon hyperpolarization of the cells. The
results indicate that the binding of MC540 to erythrocytes is strongly dependent
on the membrane potential and that hyperpolarization of the membrane could be a
possible protection mechanism for erythrocytes against MC540-mediated
photodynamic damage.
PMID- 9648539
TI - Literally changing the brain.
PMID- 9648540
TI - From sensation to cognition.
AB - Sensory information undergoes extensive associative elaboration and attentional
modulation as it becomes incorporated into the texture of cognition. This process
occurs along a core synaptic hierarchy which includes the primary sensory,
upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones
of the cerebral cortex. Connections from one zone to another are reciprocal and
allow higher synaptic levels to exert a feedback (top-down) influence upon
earlier levels of processing. Each cortical area provides a nexus for the
convergence of afferents and divergence of efferents. The resultant synaptic
organization supports parallel as well as serial processing, and allows each
sensory event to initiate multiple cognitive and behavioural outcomes. Upstream
sectors of unimodal association areas encode basic features of sensation such as
colour, motion, form and pitch. More complex contents of sensory experience such
as objects, faces, word-forms, spatial locations and sound sequences become
encoded within downstream sectors of unimodal areas by groups of coarsely tuned
neurons. The highest synaptic levels of sensory-fugal processing are occupied by
heteromodal, paralimbic and limbic cortices, collectively known as transmodal
areas. The unique role of these areas is to bind multiple unimodal and other
transmodal areas into distributed but integrated multimodal representations.
Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampal
entorhinal complex and the posterior parietal cortex provide critical gateways
for transforming perception into recognition, word-forms into meaning, scenes and
events into experiences, and spatial locations into targets for exploration. All
cognitive processes arise from analogous associative transformations of similar
sets of sensory inputs. The differences in the resultant cognitive operation are
determined by the anatomical and physiological properties of the transmodal node
that acts as the critical gateway for the dominant transformation. Interconnected
sets of transmodal nodes provide anatomical and computational epicentres for
large-scale neurocognitive networks. In keeping with the principles of
selectively distributed processing, each epicentre of a large-scale network
displays a relative specialization for a specific behavioural component of its
principal neurospychological domain. The destruction of transmodal epicentres
causes global impairments such as multimodal anomia, neglect and amnesia, whereas
their selective disconnection from relevant unimodal areas elicits modality
specific impairments such as prosopagnosia, pure word blindness and category
specific anomias. The human brain contains at least five anatomically distinct
networks. The network for spatial awareness is based on transmodal epicentres in
the posterior parietal cortex and the frontal eye fields; the language network on
epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network
on epicentres in the hippocampal-entorhinal complex and the amygdala; the face
object recognition network on epicentres in the midtemporal and temporopolar
cortices; and the working memory-executive function network on epicentres in the
lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual
sensory modalities give rise to streams of processing directed to transmodal
nodes belonging to each of these networks. The fidelity of sensory channels is
actively protected through approximately four synaptic levels of sensory-fugal
processing. The modality-specific cortices at these four synaptic levels encode
the most veridical representations of experience. Attentional, motivational and
emotional modulations, including those related to working memory, novelty-seeking
and mental imagery, become increasingly more pronounced within downstream
components of unimodal areas, where they help to create a highly edited
subjective version of the world. (ABSTRACT TRUNCATED)
PMID- 9648541
TI - The illiterate brain. Learning to read and write during childhood influences the
functional organization of the adult brain.
AB - Learning a specific skill during childhood may partly determine the functional
organization of the adult brain. This hypothesis led us to study oral language
processing in illiterate subjects who, for social reasons, had never entered
school and had no knowledge of reading or writing. In a brain activation study
using PET and statistical parametric mapping, we compared word and pseudoword
repetition in literate and illiterate subjects. Our study confirms behavioural
evidence of different phonological processing in illiterate subjects. During
repetition of real words, the two groups performed similarly and activated
similar areas of the brain. In contrast, illiterate subjects had more difficulty
repeating pseudowords correctly and did not activate the same neural structures
as literates. These results are consistent with the hypothesis that learning the
written form of language (orthography) interacts with the function of oral
language. Our results indicate that learning to read and write during childhood
influences the functional organization of the adult human brain.
PMID- 9648542
TI - Learning from the pupil: a spatial visual channel in the absence of V1 in monkey
and human.
AB - The pupil of the normal human subject constricts in response not only to average
increases in light energy, but also selectively to the spatial structure of a
visual stimulus even when there are no energy changes. This enables one to
measure visual acuity and sensitivity as a function of spatial frequency. It is
known that pupillometric measures of acuity correlate well with those determined
psychophysically for normal human observers. The purpose of the present study was
to measure pupillary changes with stimuli delivered to the 'blind' hemifields of
monkeys with unilateral V1 removal, and also with stimulation of a human subject
(G.Y.) with putative V1 destruction. The results show that there are small but
reliable pupillary changes to flux-equated gratings in the blind fields both in
monkeys and human. The response profile in both species is very similar: it is
narrowly tuned, with a peak at approximately 1 cycle/degree and a cut-off acuity
of approximately 7 or 8 cycles/degree, a significant reduction compared with the
intact hemifield. The result also maps well onto the psychophysically determined
spatiotemporal response profile to gratings in the blind field, as determined
independently for G.Y. Thus, there is a narrowly tuned spatial visual channel
that does not require the integrity of V1 in monkey or human. There was no
evidence under these particular conditions in either monkeys or subject G.Y. of a
pupillary response to an equiluminant change from white to green or red in the
hemianopic field. The pupil holds promise as a non-verbal, indirect method for
determining the spatial profile, sensitivity and other properties of residual
visual capacity, both in animals and humans.
PMID- 9648543
TI - Spontaneous sharp waves in human neocortical slices excised from epileptic
patients.
AB - Human neocortical temporal lobe tissue resected for treatment of
pharmacoresistant epilepsy was investigated. In slices prepared from this tissue,
field potentials sometimes superimposed by population spikes were found to appear
spontaneously. In individual slices, they were generalized or highly localized to
a field of approximately 200 microns in diameter. Synchronous with these
potentials, hyperpolarizing and depolarizing postsynaptic potentials were
recorded from neurons in the vicinity of the field potential electrode.
Hyperpolarizing postsynaptic potentials appeared to be mainly chloride mediated.
All potentials, i.e. sharp field potentials as well as postsynaptic potentials,
were reversibly suppressed by blockade of the non-NMDA (non-N-methyl-D-aspartate)
glutamate-subreceptor and of the GABAA (gamma-aminobutyric acid) receptor, and by
application of the organic calcium channel blocker verapamil. By contrast, all
potentials remained unaffected by blockade of the NMDA glutamate-subreceptor and
the GABAB receptor. The antiepileptic drugs carbamazepine and phenytoin failed to
suppress the spontaneous potentials at therapeutic concentrations. Washout of
Mg2+ from the superfusate left the spontaneous potentials unchanged or converted
them to ictal-type discharges. This epileptiform activity was not suppressed, but
augmented by blockade of the GABAA receptor. As a whole, the spontaneously
appearing field potentials may be assumed to reflect a state of increased
neuronal synchronization.
PMID- 9648544
TI - Nitric oxide-induced oxidative stress in autosomal recessive and dominant
inclusion-body myopathies.
AB - Autosomal-recessive and autosomal-dominant hereditary inclusion-body myopathies
are severe, progressive muscle diseases, characterized pathologically by
vacuolated muscle fibres containing paired helical filaments. We immunostained
muscle biopsy specimens from quadriceps-sparing autosomal-recessive and autosomal
dominant inclusion-body myopathy subjects, disease-control subjects and normal
patients, utilizing isoform-specific antibodies against the neuronal and
inducible forms of nitric oxide synthase, and antibodies against nitrotyrosine.
Approximately 75% of the vacuolated muscle fibres in all recessive and dominant
inclusion-body myopathy patients contained inclusions strongly immunoreactive
with antibodies against neuronal and inducible nitric oxide synthase which, by
immunoelectron microscopy, were colocalized to clusters of tubulofilaments
(previously shown, by us, to be paired helical filaments). Strong nitrotyrosine
immunoreactivity was in the form of multiple dots and large granular patches,
which ultrastructurally did not immunolocalize to tubulofilaments. Excess
intracellular nitric oxide can combine with superoxide to produce highly toxic
peroxynitrite, which can nitrate tyrosines of proteins. The presence of
nitrotyrosine is indicative of nitric oxide-induced oxidative stress. Our data
suggest that oxidative stress plays a role in the pathogenic cascade of
hereditary inclusion-body myopathies.
PMID- 9648545
TI - Corticobulbar tract involvement in amyotrophic lateral sclerosis. A transcranial
magnetic stimulation study.
AB - We investigated corticobulbar tract function by recording from the tongue and
orofacial muscles and using transcranial magnetic stimulation (TMS) in 30
patients with amyotrophic lateral sclerosis (ALS) in order to improve the
diagnostic yield in the detection of subclinical upper motor neuron (UMN)
dysfunction. A UMN lesion was assumed when the peripheral conduction time and
amplitude of the M-wave were within normal range and either the response to
cortical stimulation was absent, or the central conduction time was delayed (>
mean + 2.5 SD). Only two patients showed clinical evidence of UMN involvement in
the cranial nerves, while TMS demonstrated corticobulbar tract dysfunction in the
orofacial muscles in 17 patients (57%) and to the tongue in 15 patients (50%).
Following recording at both sites, corticobulbar tract dysfunction was confirmed
in 21 patients (70%). Twelve out of 13 patients with bulbar symptoms had evidence
of additional subclinical corticobulbar tract involvement using TMS. In seven out
of 15 patients with isolated limb involvement, subclinical corticobulbar tract
dysfunction was demonstrated. Our results indicate the presence of early and, in
most cases, subclinical corticobulbar tract involvement in the pathways to the
orofacial muscles and tongue in ALS.
PMID- 9648546
TI - Central motor conduction time in progressive multiple sclerosis. Correlations
with MRI and disease activity.
AB - The purpose of this study was to relate abnormalities of motor conduction time to
the presence of spinal cord MRI lesions in progressive multiple sclerosis and to
investigate the relationship between changes in motor conduction over time and
clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the
brain and spinal cord, and clinical evaluations were carried out in 20 patients
with primary and secondary progressive multiple sclerosis. CMCT was carried out
at the beginning and end of the study whilst the clinical and MRI examinations
occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis
brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior
correlated with disability measured on the Expanded Disability Status Scale.
Latencies to upper limb muscles correlated with cervical MRI lesion load and the
presence of atrophy of the cervical cord. Over the 12-month study period, 15 of
19 patients deteriorated clinically. However, an increase in motor response
latencies occurred only in the four patients who had developed new cord lesions.
The results suggest that prolonged CMCT is related to spinal cord lesion load and
that, over time, changes in the CMCT occur only when spinal cord lesion load
increases. Clinical change in progressive multiple sclerosis may therefore occur
without either the development of new lesions on MRI scans or an increase in
motor conduction time. This suggests that clinical deterioration in these
patients may occur by a mechanism other than increasing demyelination. This may
be progressive axonal degeneration.
PMID- 9648547
TI - Ocular search during line bisection. The effects of hemi-neglect and hemianopia.
AB - We examined ocular fixations during line bisection in five patients with left
hemianopia, two patients with right hemianopia, nine patients with left hemi
neglect and nine normal control subjects. Compared with measures in control
subjects, the median fixation, and left- and rightmost fixations were shifted
contralaterally in patients with hemianopia alone and ipsilaterally in patients
with hemi-neglect. The fixation with the longest duration and the bisection point
were also shifted contralaterally with hemianopia and ipsilaterally with hemi
neglect. However, the number of fixations and the spatial range spanned by
fixations did not differ between the groups, showing that ocular exploration was
not truncated in any group. Only some patients showed a previously reported
directional search bias. Overall, there was no directional bias in saccadic
number or amplitude. The distribution of fixations was most dense at the centre
of the line in normal subjects, while hemianopic patients fixated most frequently
at the ends of lines in their contralateral (blind) hemispace and at a central
locus that was biased slightly contralaterally, as was their bisection judgement.
This contralateral bias may reflect either an adaptive contralateral attentional
gradient or a non-veridical spatial representation within the remaining normal
hemifield. Hemi-neglect patients had a broad distribution of fixation peaks in
the ipsilateral hemispace. Of two hemi-neglect patients with many fixations, one
clustered fixations at a position right of centre, as if a normal fixation
pattern was shifted rightward, while the other had two fixation peaks: one to the
far right and the other near the centre of the line, reminiscent of the dual
peaks of activity seen in some recent hemi-neglect models. These data reveal a
heterogeneity in the routes by which right-biased judgements of spatial centre
are reached by hemi-neglect patients.
PMID- 9648548
TI - Distinct time courses of word and context comprehension in the left temporal
cortex.
AB - The time course and cortical basis of reading comprehension were studied using
magnetoencephalography. The cortical structures implicated most consistently with
comprehension were located in the immediate vicinity of the left auditory cortex,
where final words totally inappropriate to the overall sentence context evoked
enduring activation starting approximately 250 ms and lasting up to 600 ms after
word onset. Contextually appropriate but unexpected words produced weaker
activation which terminated earlier. Highly anticipated words totally failed to
activate this area, suggesting that the conceptual network became involved only
if unexpected information was detected during the primary word identification
process. We propose that the point in time (350 ms after word onset) where the
response to appropriate but unexpected endings started to diverge from those to
contextually inappropriate endings reflects the boundary between understanding a
single word and the meaning of a whole sentence.
PMID- 9648549
TI - Aversive gustatory stimulation activates limbic circuits in humans.
AB - Animal studies implicate the amygdala and its connections in the recognition of
aversive stimuli. A recent PET study demonstrated that the human amygdala and
left orbitofrontal cortex show substantial increases in regional cerebral blood
flow (rCBF) during exposure to aversive odourants. To examine if aversive
gustatory stimuli similarly activate these regions, nine healthy women tasted an
aversive saline solution, pure water and chocolate while rCBF was measured with
PET. The aversive saline condition, when contrasted with the water condition,
increased activity in the right amygdala, left anterior orbitofrontal cortex,
medial thalamus, pregenual and dorsal anterior cingulate, and the right
hippocampus. The right amygdala, left orbitofrontal cortex and pregenual
cingulate remained significantly activated when saline was compared with
chocolate. The present results indicate that the amygdala and orbitofrontal
cortex respond to aversive stimuli in both the olfactory and gustatory
modalities, and highlight the role of the pregenual cingulate in negative
emotional processing.
PMID- 9648550
TI - Differential effect of a dopaminergic agonist on prefrontal function in traumatic
brain injury patients.
AB - We examined the effects of low-dose bromocriptine, a D2 dopamine receptor
agonist, on processes thought to be subserved by the prefrontal cortex, including
working memory and executive function, in individuals with traumatic brain
injury. A group of 24 subjects was tested using a double-blind, placebo
controlled crossover trial, counterbalanced for order. Bromocriptine was found to
improve performance on some tasks thought to be subserved by prefrontal function,
but not others. Specifically, there was improvement in performance on clinical
measures of executive function and in dual-task performance, but not measures
that tap the ability to maintain information in working memory without
significant executive demands. Also, on control tasks not thought to be dependent
on the prefrontal cortex, no improvement on bromocriptine was noted. These
results demonstrate a selective effect of bromocriptine on cognitive processes
which involve executive control, and provide a foundation for potential therapies
for patients with prefrontal damage causing dysexecutive syndromes.
PMID- 9648551
TI - Ocular tracking of step-ramp targets by patients with unilateral cerebral
lesions.
AB - The relationship of sinusoidal smooth pursuit defects to pursuit defects with
step-ramp targets in patients with cerebral lesions is unclear. We examined
pursuit and saccades to both step-ramp and sinusoidal targets in 17 patients with
unilateral cerebral lesions. Two types of pursuit defects were found. One group
of three patients had ipsi-directional sinusoidal pursuit defects from lesions to
the posterior internal capsule. Their chief abnormality with step-ramp targets
was increased contra-directional pursuit. Their ipsi-directional step-ramp
pursuit was often normal and disproportionately better than their ipsi
directional sinusoidal pursuit. Another patient with a parietal lesion had a
second type of pursuit defect. He had low-normal sinusoidal pursuit bilaterally,
but decreased ipsi- and contra-directional step-ramp pursuit. Also, he had an
abnormal contra-directional drift after saccades to stationary targets. Despite
these pursuit defects, saccadic accuracy did not show poor compensation for
target motion in either patient type. The patient with the parietal lesion also
had increased latencies for contralateral saccades. Recovery of pursuit was
studied in one patient with an infarct of the posterior internal capsule.
Initially he had a contra-directional bias that caused decreased ipsi-directional
pursuit, increased contra-directional pursuit, and a contra-directional drift
after saccades to stationary targets. Four months later, ipsi-directional pursuit
and the post-saccadic drift to stationary targets had recovered, but contra
directional pursuit remained abnormally high. We conclude that lesions of
descending pursuit tracts in the internal capsule are characterized by a contra
directional bias which recovers partly through a direction-specific adaptation.
Lesions that affect the human homologue of posterior parietal cortex cause
asymmetric bi-directional defects in pursuit initiation and increased
contralateral saccadic latencies.
PMID- 9648552
TI - Molecular genetics of renal cell carcinoma.
AB - Renal cell carcinoma (RCC) is an important clinical problem for which an
effective treatment has yet to be developed. Importantly, the 5-year survival is
below 50%. A better understanding of the underlying biological mechanisms could
result in improvements in the prevention and treatment of this disease. The
molecular mapping of chromosomal losses in renal cell cancer together with
increased resolution of the human gene map will provide targets for therapeutic
approaches. In this review, I summarize what is known regarding some tumor
suppressor genes and candidate tumor suppressor genes in RCC, with reference to
their location and expression.
PMID- 9648553
TI - A recurrent nonrandom translocation (3;7)(q27;p12) associated with BCL-6 gene
rearrangement in B-cell diffuse large cell lymphoma.
AB - Two cases of B-cell diffuse large cell lymphoma associated with the
t(3;7)(q27;p12) and BCL-6 rearrangement are described. Cytogenetic studies
revealed [case 1] 47,XY,t(3;7)(q27;p12),+12 and [case 2] 45,X,
Y,t(3;7)(q27;p12),del(6)(q21q25),+16,-21. The translocation of each case had a
non-random chromosomal change involving a 3q27 locus associated with BCL-6 gene
rearrangement identified by Southern blot analysis. Both cases involved multiple
lymph nodes and extranodal regions, such as stomach and peritoneal cavity in case
1, extranodal retroperitoneal space, subcutis, probable liver, and colon in case
2. Chemotherapy provided only short survival after onset: 17 and 16 months,
respectively. Altered expression of adhesion molecules CD44, CD54 (case 1) and
CD11a and CD18 (case 2) may help to explain the poor outcome of these patients.
PMID- 9648554
TI - Translocation (10;11)(p13;q13) and MLL gene rearrangement in a case of AML (M5a)
with aggressive leukemia cutis.
AB - A male patient with a secondary acute monocytic leukemia whose leukemia cells had
a t(10;11)(p13;q13) chromosomal abnormality is described. Gene analysis disclosed
that the patient's leukemia cells had MLL gene rearrangement. His leukemia cells
responded poorly to chemotherapy, and the patient developed an unusual aggressive
leukemia cutis. A t(10;11)(p13;q13) chromosomal abnormality that expresses MLL
gene rearrangement has not been reported previously in secondary leukemia.
PMID- 9648555
TI - Genetic alterations in colorectal cancer, comparative analysis of deletion
events, and point mutations.
AB - Although data on genetic alterations leading to the development of colorectal
cancer are abundant, no specific genetic alteration, as has been demonstrated for
certain rare tumors such as lymphoma, leukemia, or sarcoma, has been shown to be
responsible for the development of colorectal carcinomas. The colorectal cancer
phenotype undoubtedly originates from an accumulation of different genetic
alterations. The nature of these alterations, their order of appearance, and
their associations vary greatly from one tumor to another, suggesting that the
concept of a unique model of carcinogenesis is not applicable to these tumors. We
studied a panel of 40 colorectal tumors in an attempt to identify different
carcinoma subsets distinguishable by the pattern of genetic alterations. We
examined a series of genetic anomalies frequently implicated in the development
of colorectal cancer, including genetic material loss, demonstrated by loss of
heterozygosity on chromosome arms 1p, 17p, and 18q; mutations of proto-oncogene K
RAS codons 12, 13, and 61; and gene TP53 mutations, identified by studying the
accumulation of the corresponding immunohistochemically detectable protein. Our
findings showed an important correlation between the genetic material loss events
and an independent distribution of point mutations, which favors the hypothesis
of a specific type of genetic instability characterized by the recurrent loss of
chromatin fragments implicated in a subset of colorectal cancers.
PMID- 9648556
TI - Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in
such tumors and results of a multicentric study.
AB - Hepatoblastoma is a rare pediatric malignant tumor of the liver. Previous
cytogenetic reports are sporadic. We karyotyped nine consecutive hepatoblastomas
from the Italian centers participating in a multicentric study on hepatic tumors
(SIOPEL 1). Six cases showed abnormal karyotypes. The most common abnormalities
were trisomies of chromosomes 2 and 20. Four cases showed abnormalities of
chromosome 1. On the basis of findings, we speculate the possibility of a
cytogenetic evolutive pattern of hepatoblastomas.
PMID- 9648557
TI - Frequency of clonal B lymphocytes in chronic myelogenous leukemia evaluated by
fluorescence in situ hybridization.
AB - The demonstration of the Philadelphia (Ph) chromosome in B lymphocytes from
patients with chronic myelogenous leukemia (CML) has provided evidence that the
disorder originates in a pluripotent progenitor cell. Divergent results, however,
exist as to the degree of contribution of clonally derived cells to the B-cell
compartment. To address this issue, B lymphocytes were selected from the blood of
seven patients in the chronic phase of Ph-positive CML and were examined with
dual-color fluoresence in situ hybridization for the presence of the Ph
translocation. The purity of the B-cell preparations ranged from 88% to 97% (mean
93%). The Ph translocation was detected in 22-34% (mean, 27%) of the sorted B
cells. There was no evidence that the duration of the disease affects the ratio
of Ph-positive and -negative B cells. In summary, clonally derived circulating B
lymphocytes were present in all patients studied but made only minor contribution
to this compartment.
PMID- 9648558
TI - Search for chromosome instability in lymphocytes with germ-line mutations in DNA
mismatch repair genes.
AB - All colorectal cancer results from the accumulation of critical genetic
alterations; however, the mechanisms of acquiring these mutations appear to be
different in hereditary nonpolyposis colon cancer (HNPCC) and sporadic tumors
with microsatellite instability compared with sporadic tumors with no
microsatellite instability. To further explore the possible mechanisms of cancer
predisposition in HNPCC, we studied chromosome breakage and induction of
aneuploidy in the lymphoblastoid cell lines of four patients who were
heterozygous for mutations in either hMSH2 or hMLH1--two components of the DNA
mismatch repair complex. Cells were cultured under different stress systems,
including exposure to bleomycin, mitomycin C, bromodeoxyuridine-induced sister
chromatid exchange, and a DNA alkylator, N-methyl-N'-nitro-N-nitrosoguanidine. No
significant differences were detected in the levels of major or minor chromosome
breakage or aneuploidy compared with controls. These results suggest that a
single "hit" to a DNA mismatch repair gene does not confer appreciable
susceptibility to structural or numerical chromosomal alterations, which is
consistent with previous observations that HNPCC-related cancers are more likely
to be near diploid than are sporadic colon cancers.
PMID- 9648559
TI - Cytogenetic analysis of a scapular chondromyxoid fibroma.
AB - Chondromyxoid fibroma (CMF) is a rare cartilaginous tumor of bone. It typically
presents in the lower extremities of young males. Cytogenetic analysis of two
chondromyxoid fibromas has been previously reported. We studied a scapular CMF
from an 11-year-old female by cytogenetic and molecular cytogenetic methods and
found an unbalanced reciprocal translocation between the short arm of chromosome
3 and the long arm of chromosome 6. In this translocation, several bands from
chromosome 3 (3p12, 3p13, 3p14, 3p21) are lost and several bands on chromosome 6
(6q21, 6q22, 6q23) appear rearranged. Two known cartilage-related genes are
located in the regions affected by this unbalanced rearrangement: the type X
collagen gene (COL10A1) located at 6q21-q22 and the parathyroid
hormone/parathyroid hormone-related peptide receptor gene (PTH/PTHrP) located at
3p21.1-p22. These genes function to control growth and maturation of endochondral
bone, the site of origin of cartilaginous tumors.
PMID- 9648560
TI - The ABL/BCR fusion gene on chromosome 9 in Ph-negative chronic myelogenous
leukemia: a case for vigilance in fluorescence in situ hybridization
interpretation.
AB - We report cytogenetic, fluorescence in situ hybridization (FISH), and molecular
analysis in a case of Ph-negative chronic myelogenous leukemia patient with
ABL/BCR fusion gene on chromosome 9 and a disparate FISH signal pattern using two
commercially available bcr/abl probes (Vysis, Inc. and Oncor, Inc.). Cytogenetic
analysis revealed a 46,XX normal female karyotype. FISH studies using Vysis LSI
bcr/abl probe in interphase cells demonstrated a BCR/ABL fusion pattern, similar
to that of m-BCR/ABL fusion found in acute lymphoblastic leukemia. However,
examination of metaphases revealed the ABL/BCR fusion signal on one of the
chromosomes 9, an ABL signal on the other chromosome 9, and two BCR signals of
different sizes on each of the chromosomes 22. Subsequently, a FISH study with
the Oncor major (M)-bcr/abl translocation probe confirmed the ABL/BCR fusion
signal on chromosome 9 in addition to an ABL signal and a BCR signal located on
chromosomes 9 and 22, respectively. Molecular studies (RT-PCR) revealed a
rearrangement of the M-BCR region and expression of a chimeric bcr/abl mRNA of
b3a2 configuration. This case suggests that it is imperative to have a full
understanding of both the capabilities and the limitations of bcr/abl
translocation probes and that FISH interphase signals should be confirmed on
metaphase spreads for accurate diagnosis.
PMID- 9648561
TI - Isochromosome 7q and Wilms tumor.
AB - Isochromosome 7q is a nonrandom cytogenetic abnormality in Wilms tumor. Two
notable cases are described: (1) a case of bilateral Wilms tumor in which only
the left-sided tumor contained isochromosome 7q and (2) a case of left-sided
Wilms tumor in which the tumor contained isochromosome 7q, in addition to four
other chromosomal abnormalities associated with Wilms tumor.
PMID- 9648562
TI - Translocation (3;21;8)(q21;q22;q22) in a patient with acute myeloid leukemia. A
case report and review of prognostic indicators.
AB - We report a patient with acute myeloid leukemia (AML) and t(3;21;8)(q21;q22;q22).
This translocation has not been previously described in de novo or relapsed AML.
The patient is a 25-year-old woman who presented with WBC 6.2 x 10(9)/L, Hgb 10.2
g/dL, Hct 28.4%, and platelets 67 x 10(9)/L. A bone marrow biopsy revealed a 70%
hematopoietic cellularity with 65% blasts. Immunophenotyping showed aberrant
expression of lymphoid-associated marker CD19. Cytogenetic analysis on a 72-hour
culture of bone marrow cells supplemented with conditioned media was evaluated by
G-banding at about the 400-band level. The patient's age, cytogenetics, WBC, and
immunophenotype at diagnosis would seem to suggest a favorable prognosis,
according to previous studies of prognostic indicators. She was treated with
induction and consolidation chemotherapy, followed by myeloablative conditioning
and autologous peripheral blood stem cell transplant (PBSCT). Despite multiple
favorable prognostic factors, the patient relapsed 7 months after PBSCT.
Translocation of chromosomes 8 and 21 is common in AML and is generally
considered a good prognostic factor. We suspect that the effect of the 3q21
translocation in an otherwise favorable translocation of chromosomes 8 and 21 may
be responsible for this patient's early relapse.
PMID- 9648563
TI - A novel t(7;17)(q11;q11) as the sole karyotypic abnormality in childhood pre-B
cell acute lymphoblastic leukemia.
PMID- 9648564
TI - Translocation (9;22;21) in a chronic myeloid leukemia fluorescence in situ
hybridization definition.
PMID- 9648565
TI - Distinct features for chromophilic renal cell cancer with Xp11.2 breakpoints.
PMID- 9648566
TI - Improvement of infraorbital hyperpigmentation following carbon dioxide laser
resurfacing.
AB - BACKGROUND: Many patients who request cutaneous carbon dioxide (CO2) laser
resurfacing for correction of periorbital rhytides also complain of "dark
circles" under their eyes. OBJECTIVE: This study was conducted in order to
determine the effectiveness of high-energy pulsed CO2 laser treatment in reducing
infraorbital hyperpigmentation. RESULTS: Significant lightening of infraorbital
hyperpigmentation was observed 9 weeks following CO2 laser resurfacing. Melanin
reflectance spectrometry readings did not correlate with clinical findings.
CONCLUSIONS: This study represents the first report of the successful use of a
non-pigment-specific laser system for the treatment of infraorbital dark circles.
The lack of correlation of melanin spectrometry readings with clinical assessment
likely represents an insufficient follow-up time period.
PMID- 9648567
TI - Treatment of photoaged neck skin with the pulsed Erbium:YAG laser.
AB - BACKGROUND: The Erbium (Er):YAG laser represents a new laser approach for the
treatment of rhytids and photodamaged skin. Because the Er:YAG laser's 2940-nm
wavelength is at the peak of water absorption, this laser produces minimal
thermal damage. OBJECTIVE: To document the Er:YAG laser's efficacy in the
treatment of neck rhytids. METHODS: Ten patients with neck rhytids were treated
with the Er:YAG laser. All individuals were evaluated for clinical improvement,
scarring, and pigmentary changes. RESULTS: All patients showed fair to excellent
results with no scarring or pigmentary changes at 6 months. CONCLUSION: The
Er:YAG laser may be used to improve nonfacial photodamaged skin.
PMID- 9648568
TI - Rapid Fire Hair Implanter Carousel. A new surgical instrument for the automation
of hair transplantation.
AB - BACKGROUND: As hair transplantation evolved into a procedure in which large
numbers of very small grafts are moved in a single session, new problems have
emerged. These include greater staffing requirements, longer operating time,
additional technical difficulties, and increasing problems with quality control.
OBJECTIVE: To introduce a new surgical instrument, the Rapid Fire Hair Implanter
Carousel (Carousel), which can automate the most labor-intensive parts of the
hair transplantation process, site creation and implant placement, by combining
them into a single step and delivering them in rapid sequence. This
instrumentation should help to minimize some of the human factors contributing to
graft injury and to simplify and increase the speed of the hair transplant
procedure. METHODS: In a patient with a Norwood IIIA balding pattern, 400
follicular implants were placed into a specific section of the bald scalp. The
remainder of the bald scalp was transplanted with 800 follicular implants placed
in the traditional way. The two areas were monitored and compared for
intraoperative bleeding, ease of placing, total placing time, postoperative
healing, and hair growth. Photographic documentation was obtained after surgery
and at each postoperative visit. RESULTS: The Carousel visually produced less
bleeding when compared with the manual approach. The Carousel was easier to use
than the manual technique, since it eliminated graft insertion as a separate
step. This was evidenced by the significantly shorter time required to insert the
implants (40 grafts/minute with the Carousel vs 6.6 grafts/minute manually) and
the decreased need for secondary manipulation once the grafts were inserted.
Postoperative healing of the two groups were the same with regard to the duration
of crusting and erythema. The rate of hair growth and the total amount of hair
observed at 4 months were the same when identical size areas in test and control
sides were compared. CONCLUSION: In this single patient pilot study, the Carousel
greatly facilitated the placement of grafts by decreasing bleeding and obviating
the extra step needed for the insertion of the implants. As a result, the total
operative time decreased, shortening the time the grafts were outside the body,
and decreasing the risk of desiccation and warming. By minimizing the human
factor in this labor-intensive part of the procedure, the quality of the hair
transplant should increase. It is anticipated that these benefits will result in
increased hair yield. Further studies are needed, in a larger patient group, so
that these benefits can be demonstrated.
PMID- 9648569
TI - New instrumentation for hair transplantation surgery.
AB - This article introduces new instrumentation to the field of hair transplantation
surgery. These new instruments include differential spear blades for better
sharpness and versatility, a graft counter for facilitation of the counting
process, a blade holder with a direction guide to help the doctor with proper
direction of recipient incisions, a cushioned forceps to soften the trauma to the
hair grafts as they are being inserted, a compass to help construct the posterior
crown, and a temperature probe that constantly monitors the temperature of the
saline solution that is keeping the hair grafts cool. This instrumentation has
significantly facilitated and improved the hair transplantation process.
PMID- 9648570
TI - Alabaster skin after carbon dioxide laser resurfacing with histologic
correlation.
AB - BACKGROUND: Carbon dioxide laser resurfacing has gained popularity as a
relatively safe and effective method of facial rejuvenation. Original reports
describe mostly reversible side effects and a low incidence of scarring. Only
very recently have reports of delayed hypopigmentation surfaced. This effect is
not visible until several months after resurfacing, and most likely represents a
permanent change. OBJECTIVE: To provide an additional clinical description of the
complication of delayed hypopigmentation along with the first published
histologic correlation. METHODS: Clinical records along with a preprocedure and 7
month postprocedure full-thickness skin biopsy were used for this report.
RESULTS: This patient experienced a striking leukoderma 6 months after a full
facial carbon dioxide laser resurfacing procedure done for widespread actinic
keratoses. There was a zone of dermal fibrosis extending approximately 0.4 mm on
the postprocedure biopsy. Comparison of the preprocedure and postprocedure
biopsies revealed no difference in the number of melanocytes by MART-1
immunohistochemical staining, but there was a significant decrease in epidermal
melanin as determined by Fontana-Mason staining. CONCLUSION: This patient
experienced a profound expression of an increasingly recognized and reported
complication of carbon dioxide laser resurfacing. Histologic correlation is
similar to the results previously reported after phenol chemical peels,
demonstrating a normal number of melanocytes but a decrease in epidermal melanin.
PMID- 9648571
TI - The roles of pH and concentration in lactic acid-induced stimulation of epidermal
turnover.
AB - BACKGROUND: Alpha hydroxy acids such as lactic and glycolic acids (AHAs)
accelerate epidermal turnover and exfoliate the stratum corneum. The roles of pH
and concentration in these antiaging effects of AHAs is unclear, but a lower
(more acidic) pH and higher concentration of acid are thought to be more
effective. OBJECTIVE: To examine the effects on skin renewal rates of lactic acid
10% at pHs of 2.0, 3.0, and 4.0, and of 5%, 10% and 15% lactic acid at a pH of
3.0. METHODS: Twenty-six female subjects participated in the double-blind,
randomized, placebo-controlled study. The dansyl chloride stain technique was
used to measure epidermal renewal times. RESULTS: Both pH and concentration are
critical in the lactic acid effect. At a fixed lactic acid concentration, the
desquamative effect was highly pH dependent. At a fixed pH, the turnover rate of
skin was concentration dependent. CONCLUSION: The desquamative and proliferation
stimulating effects of lactic acid are very pH and concentration dependent,
suggesting the "free acid" concentration is the active moiety.
PMID- 9648572
TI - Comparison of high-energy pulsed carbon dioxide laser resurfacing and
dermabrasion in the revision of surgical scars.
AB - BACKGROUND: Both dermabrasion and high-energy pulsed carbon dioxide (CO2) laser
resurfacing can improve the appearance of surgical scars. Although the results of
these two procedures have been compared using historical data, a prospective
evaluation has never been performed in humans. OBJECTIVE: To prospectively
compare the clinical effects of dermabrasion and high-energy pulsed CO2 laser
resurfacing in the revision of surgical scars. METHODS: Facial surgical scars in
four patients were prospectively revised using a split scar model. One half of
the scar was dermabraded and the other half was resurfaced with the high-energy
pulsed CO2 laser. Comparisons of the two treatment modalities were performed
through clinical assessment, photographic evaluation, and textural analysis of
the scars. RESULTS: The high-energy pulsed CO2 laser-resurfaced halves of the
scar were bloodless with less postoperative crusting in comparison with the
dermabraded halves. Reepithelialization time and degree and duration of
postoperative erythema were similar for both treatment halves. Photographic
evaluation and textural analysis showed comparable improvement in the clinical
appearance and surface texture of the scars with both treatment modalities.
CONCLUSIONS: Both the high-energy pulsed CO2 laser and dermabrasion can achieve
comparable clinical improvement in the revision of surgical scars. The high
energy pulsed CO2 laser offers the advantage of a bloodless field and a more
precise method of tissue ablation. Postoperative erythema, however, is an
expected finding with both treatment modalities.
PMID- 9648573
TI - Skin resurfacing of the face with the Erbium:YAG laser.
AB - BACKGROUND: Laser resurfacing of facial skin is a very popular method of rhytide
and scar removal. Until recently, the most effective tool utilized for these
purposes was the pulsed char-free carbon dioxide laser. These lasers, however,
produce thermal damage related to prolonged wound healing. The Erbium (Er): YAG
laser, with its 2940-nm wavelength and maximal water absorption, has been
recently introduced for laser resurfacing of the facial skin. OBJECTIVE: In this
study, specific parameters for Er:YAG laser treatment of rhytides were evaluated
clinically and histologically. METHODS: Fifteen patients were treated with the
Er:YAG laser. Perioral, periorbital, and total face rhytides were treated. All
patients were treated with 0.8-1.0 J, 5-mm spot size, with the final fluences of
4-5 J/cm2. Patients were evaluated daily after treatment for 7 days and weekly
for 2 months for erythema, healing time, improvement, and pigmentary changes.
Histologic evaluation of preauricular human facial ex vivo skin was done to
determine the penetration of multiple passes of Er:YAG laser in human facial
skin. RESULTS: All patients showed some degree of improvement of their rhytides.
Reepithelialization occurred between 3 and 8 days. All evidence of erythema
resolved between 3 and 6 weeks after treatment. The level of tissue ablation was
determined to be down to: the granular layer after one pass; to the basal cell
layer after two passes, to the papillary dermis after three to four passes, and
deeper into the papillary and superficial reticular dermis after five to six
passes. CONCLUSION: The Er:YAG laser plays a significant role in the treatment of
superficial and mid-depth rhytides.
PMID- 9648574
TI - Accelerated laser resurfacing wound healing using a triad of topical
antioxidants.
AB - BACKGROUND: The speed of wound healing and the duration of erythema are the
primary complaints after laser skin resurfacing. Antioxidants have been shown to
enhance the healing of wounds by reducing free radical damage.
Reepithelialization is also enhanced by the moist environment produced by
occlusive dressings. OBJECTIVE: This study was conducted to compare two occlusive
agents: white petrolatum and "melting" petrolatum. Another arm of the study
evaluated the use of melting petrolatum with and without a triad of topical
antioxidants (TTA). RESULTS: Plain white petrolatum proved superior to melting
petrolatum in time required for reepithelialization as well as in discomfort.
Crusting and pain were decreased with white petrolatum but duration of erythema
was equivalent. Wound healing was enhanced when TTA was added. Time for
reepithelialization, duration of crusting and scabbing, pain, redness, and
swelling were decreased when TTA was added to topical therapy. CONCLUSION: TTA
compound enhances and hastens wound healing. White petrolatum as a base occlusive
vehicle shortens reepithelialization compared with "melting" petrolatum.
PMID- 9648575
TI - Carbon dioxide laser resurfacing: preliminary observations on short-term follow
up. A subjective study of 100 patients' attitudes and outcomes.
AB - BACKGROUND: Carbon dioxide (CO2) laser resurfacing is enjoying broad medical
acclaim. It is useful to assess patient morbidity and satisfaction with this
procedure. OBJECTIVE: Review the procedure from the patients' perspective with
particular focus on the immediate and medium term postoperative period, the
patient's progress after the initial 6-8-week period, the postoperative morbidity
and complication rate, and the results and patient satisfaction with the
procedure. METHOD: One hundred resurfacing patients, who were treated after the
advent of the computer pattern generator on a high-energy short-pulse CO2 laser,
were studied. Patients were at least 3 months into their postoperative phase.
RESULTS: Outcomes of patients' problems were classed as good to excellent 78.8%
of the time. Patient outcomes met the patients' preoperative expectations 68.9%
of the time. Patients would have the procedure again if needed 78% of the time,
and 84% would recommend the procedure to others. Patients reported continuing
improvement after the initial 6-8-week healing period 72% of the time. Short-term
morbidity was high (49%). Long-term complications were registered in 7% of
patients but were mostly minor in nature. CONCLUSIONS: Major indications for
laser resurfacing such as wrinkles, sun damage, and acne scarring all appeared to
do well with CO2 laser resurfacing.
PMID- 9648576
TI - Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. A
follow-up study.
AB - BACKGROUND: We previously reported our experience using Mohs micrographic surgery
(MMS) for 45 patients with lentigo maligna (LM) and lentigo maligna melanoma
(LMM). The patients were treated between 1985 and 1992. In our initial
publication, all of the patients were free of local disease and evidence of
metastases at an average of 29.2 months after therapy. OBJECTIVE: The purpose of
this study was to report long-term follow-up of our previously published data.
METHODS: MMS was performed in 26 patients with LM and 19 patients with LMM using
frozen sections followed by rush permanent sections. Follow-up was obtained by
contacting the referring physician, examination by one of our two Mohs surgeons,
or by contacting the patient or his or her family. RESULTS: After a median follow
up of 58.0 months (214.3 patient-years), there was one recurrence. This patient
was a 56-year-old woman with five prior recurrences before MMS. Six patients were
decreased of other causes during the study. CONCLUSIONS: MMS using frozen and
rush permanent sections resulted in a 97% cure rate for LM and LMM. Because MMS
minimizes the removal of normal tissue, and the cure rate exceeds that of
conventional therapies, the authors recommend this technique for the treatment of
LM and LMM.
PMID- 9648577
TI - Hair tie-over dressing. A simple dressing for hair-bearing scalp wounds.
AB - OBJECTIVE: To describe a temporary dressing for Mohs micrographic surgery wounds
of the hair-bearing scalp. METHOD: The technique of using hair at the wound edges
to hold down the dressing is described. RESULTS: This is an effective, simple,
comfortable, and inexpensive scalp dressing, which our patients have found to be
very acceptable. CONCLUSION: We consider that the hair tie-over dressing is an
ideal temporary dressing for Mohs micrographic surgery wounds of the hair-bearing
scalp.
PMID- 9648578
TI - Mohs micrographic surgery for an erosive adenomatosis of the nipple.
AB - BACKGROUND: Erosive adenomatosis of the nipple is a rare but distinct benign
tumor of the nipple. It is usually considered to be derived from the apocrine
sweat ducts of the nipple epithelium but probably of lactiferous duct origin.
Total excision is the treatment of choice. OBJECTIVE: We report the clinical and
histological features of this rare tumor, and the surgical technique employed.
METHODS: Treatment consisted of Mohs micrographic surgery (MMS), fresh tissue
technique, followed by primary closure. RESULTS: The described procedure resulted
in a cure of the erosive adenomatosis of the nipple. CONCLUSION: Total excision
of erosive adenomatosis of the nipple can be obtained by MMS. This technique
prevents recurrence of the disease and minimizes resulting deformation of this
important anatomic area.
PMID- 9648579
TI - Laser resurfacing hysteria. The media, the marketers, the companies, and us.
PMID- 9648580
TI - The limitations of skin resurfacing techniques. The necessity to combine
procedures.
PMID- 9648581
TI - Titanic tumescent anesthesia.
PMID- 9648582
TI - Electrocautery for treating periorbital syringomas.
PMID- 9648583
TI - The International Society for Dermatologic Surgery's Traveling Chair of
Dermatologic Surgery Faculty and its newest member.
PMID- 9648584
TI - Multidisciplinary management of urinary pouch complications: a better way.
PMID- 9648585
TI - Management of early and late complications of ileocolonic continent urinary
reservoir (Miami pouch).
AB - PURPOSE: The object of this study is to review our experience and formulate a
plan for early recognition and effective management of early and late
complications seen in patients who have undergone construction of the ileocolonic
continent urinary reservoir. METHOD: Charts of patients who underwent continent
urinary diversion at the Division of Gynecologic Oncology, University of Miami
School of Medicine, from 1988 to 1996 were reviewed. We analyzed our data in
terms of early and late (beyond 6 weeks) complications resulting directly from
the operation or from this form of urinary diversion. RESULTS: Urinary diversion
via the continent ileocolonic reservoir has been performed at our institution
since February 1988. Sixty-six women have undergone construction of the Miami
pouch over the past 81 years. Sixty-three of 66 patients needed a reservoir as a
part of total pelvic exenteration for persistent or recurrent gynecologic
malignancy. Three patients underwent reservoir construction for repair of
vesicovaginal fistula. Sixty-two of 66 patients (95%) have a history of prior
pelvic radiation. A total of 35 patients (53%) suffered early complications
resulting in an operative mortality rate of 9% (6 of 66 patients). Early
complications related to the construction of the reservoir included ureteral
stricture/obstruction [10], anastomotic leak [4], reservoir-cutaneous fistula
[4], difficulty in catheterization [5], pyelonephritis [10], sepsis [6], DIC [2],
and ARDS [1]. Nonsurgical management strategies used for reservoir-related
complications in these cases included percutaneous nephrostomy, peripheral
hyperalimentation, intravenous antibiotics, and ultrasound-guided catheter
placement. Eighty-four percent (16/19) of functional complications of the
reservoir resolved with conservative management, whereas 3/19 patients needed
surgical revision. One or more late complications (beyond 6 weeks) occurred in 25
patients (37%). Late complications seen included ureteral stricture/obstructions
[6], incontinence [8], difficulty in catheterization [7], and urinary stones [4].
Nonsurgical management strategies used included percutaneous nephrostomy, balloon
dilation, scheduled catheterization, ultrasound-guided catheter placement, and
endoscopic/percutaneous lithotripsy. Four of 25 patients needed reoperation,
whereas in 84% (21/25) of patients problems resolved with initial conservative
management. CONCLUSION: Successful conservative therapy constitutes establishment
of drainage, adequate nutrition, avoidance of sepsis, close observation, and
patience. This article reviews the complications of the continent ileocolonic
form of urinary diversion and formulates a treatment outline emphasizing an
initial conservative approach that offers optimal management of early and late
complications seen in this patient group.
PMID- 9648586
TI - Determination of a normal level of serum CA125 in postmenopausal women as a tool
for preoperative evaluation and postoperative surveillance of endometrial
carcinoma.
AB - In an attempt to determine a normal level of CA125 in postmenopausal women, CA125
levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and
postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8
+/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was
found in postmenopausal women without HRT and was significantly lower than that
of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the
cutoff level of CA125 in postmenopausal women or women without reproductive
organs should be estimated at a level lower than that conventionally accepted. A
receiver operating characteristic (ROC) curve for a preoperative evaluation of
myometrial invasion was analyzed in postmenopausal women with endometrial cancer
(n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial
invasion to more than one-half of the myometrium with sensitivity of 69.0%,
specificity of 74.1%, positive predictive value of 58.8%, and negative predictive
value of 81.6%. In addition, the distribution of CA125 levels was analyzed in
patients who had undergone an operation for endometrial cancer more than 2 years
earlier and as yet had no clinical evidence of recurrence of the disease. Ninety
six point two percent of 619 measurement values were lower than 20 U/ml. These
results suggest that the novel CA125 level of 20 U/ml is clinically useful for
preoperative evaluation and postoperative surveillance of endometrial carcinoma.
PMID- 9648587
TI - In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer.
AB - OBJECTIVES: To test the safety, efficacy, and toxicity of gene therapy using wild
type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with
intraperitoneal (i.p.) 2774 human ovarian cancer cell line that contains a p53
mutation. STUDY DESIGN: An initial study of adenovirus tolerance was determined
in nude mice by a single i.p. injection of increasing doses of Ad-CMV-p53. Nude
mice were implanted with an LD100 dose of 1 x 10(7) cells. To study the efficacy
and specificity of Ad-CMV-p53 treatment, the mice received treatment with
different adenovirus constructs. One group received Ad-CMV-p53 and another group
received a control adenovirus construct, Ad-CMV-beta gal. To study the treatment
response to Ad-CMV-p53, the mice were divided into groups and received various
treatment schedules of 1 x 10(8) pfu of Ad-CMV-p53. RESULTS: The mice tolerated
Ad-CMV-p53 without adverse effects at doses of 1 x 10(8) pfu. The response to Ad
CMV-p53 showed significant survival duration in each dose regimen, with a
survival time greater than that of untreated animals (P = 0.0173). However, no
statistically significant survival advantage was observed between Ad-CMV-p53- and
Ad-CMV-beta gal-treated mice. CONCLUSIONS: These studies show that at the
adenovirus dose and administration regimen used, there is effective but not
specific 2774 tumor growth inhibition in vivo. Efficient introduction of
biologically active genes into tumor cells would greatly facilitate cancer
therapy. Thus, although promising, these results caution that much effort will be
required to realize the potential for clinical application of adenovirus-based
ovarian cancer gene therapy.
PMID- 9648588
TI - The status of human papillomavirus and tumor suppressor genes p53 and p16 in
carcinomas of uterine cervix from India.
AB - OBJECTIVES: Infection with the high-risk strain of human papillomaviruses (HPVs)
and the inactivation of the tumor suppressor gene p53 through mutation are
important factors in cervical carcinogenesis. To know whether such events would
occur in cervical carcinomas of Indians, 43 tumors (consisting of 36 of stage III
B and 6 of stage II B) were screened for p53 and p16 gene mutations. METHODS: PCR
followed by single-strand conformation polymorphism (SSCP) analysis were used to
detect mutations in p53 and p16 genes and PCR for the presence of human
papillomavirus genome. HPV status was ascertained by PCR amplification of parts
of E6 and E7 genes using primers pU-1M and pU-2R and typing was carried out by
restriction analysis. RESULTS: Of the 43 samples analyzed, 4 samples (9%) showed
mobility shifts for p53 mutations; PCR products of the p16 gene did not show band
shifts in SSCP analysis. HPV DNA was detected in 70% of the 43 samples analyzed:
HPV 16 in 23 cases (53%), HPV 18 in 4 cases (13.3%), and HPV 33 in 1 case (3.3%).
Two amplified HPV DNAs that were difficult to type with various restriction
enzymes were cloned and the amplified regions were sequenced. One of these was
93% close to HPV 35 and the other was 80% close to HPV 58. Three samples had both
p53 mutations and HPV genome. CONCLUSIONS: Our results indicate that HPV 16
infection was more common than HPV 18, the p53 mutations and HPV infection were
not mutually exclusive events in the genesis of carcinoma of uterine cervix among
Indian women, and p16 gene may not play a role in Indian cervical carcinomas.
PMID- 9648589
TI - No evidence for microsatellite instability from allelotype analysis of benign and
low malignant potential ovarian neoplasms.
AB - The genetic events that lead to the development of benign and low malignant
potential (LMP) tumors from normal ovarian surface epithelium are not well
understood. In contrast to invasive ovarian neoplasms, loss of heterozygosity
(LOH) is not common in these tumors except on the X chromosome, but one report
has suggested that an alternative genetic mechanism, microsatellite instability
(MSI), might be an important pathogenic mechanism for LMP ovarian tumors.
OBJECTIVE: To determine the frequency of MSI in LMP tumors and to detect novel
regions of LOH in benign and LMP ovarian tumors. METHODS: Sixty-nine
microsatellite markers were analyzed in 23 benign and 31 LMP ovarian tumors.
RESULTS: No evidence of MSI was found in any of the tumors studied, nor were any
novel regions of LOH identified. CONCLUSIONS: This suggests that new approaches
may be necessary to understand the genetic basis of benign and LMP ovarian
neoplasms since neither LOH nor MSI appears to play a major role.
PMID- 9648590
TI - Retinoblastoma protein expression in ovarian epithelial neoplasms.
AB - Progress has been made in identifying the molecular changes that occur in ovarian
carcinoma; still our understanding of these changes and their interactions
remains incomplete. In the present study the authors examined the expression of
retinoblastoma protein, a tumor suppressor protein, in a spectrum of ovarian
epithelial tumors including cystadenomas, low-malignant-potential tumors, and
carcinomas. A heterogeneous pattern of reactivity was observed in all of the
cystadenomas, in all of the low-malignant-potential tumors, and in a majority
(27/34) of the carcinomas. The remaining carcinomas showed either a complete
absence of reactivity or a pattern of altered reactivity characterized by areas
of tumor with intact reactivity adjacent to zones of tumor with a complete
absence of reactivity. There was no significant association between grade or
stage and absent/altered reactivity. We conclude that alterations of
retinoblastoma protein expression are uncommon in ovarian carcinoma.
PMID- 9648591
TI - Prognostic significance of progesterone receptor immunohistochemistry in
endometrial carcinoma.
AB - OBJECTIVE: The aim of this study was to evaluate the prognostic significance of
steroid hormone receptors in endometrial carcinoma using immunohistochemical
staining for progesterone receptor (PR) and estrogen receptor (ER). METHODS: We
evaluated the correlation between PR/ER immunohistochemistry and age, clinical
stage, tumor grade, myometrial tumor invasion, and disease-free survival in a
series of 92 cases of endometrioid adenocarcinoma. RESULTS: Fifty (54.4%)
endometrial carcinomas were PR-positive and 44 (47.8%) were ER-positive. PR
immunohistochemistry of endometrial carcinoma was statistically correlated with
the International Federation of Gynecology and Obstetrics (FIGO) stage (I, II vs
III, IV, P = 0.001), FIGO grade (G1 vs G2 vs G3, P = 0.007), the depth of
myometrial tumor invasion (< or = 1/2 vs > 1/2, P = 0.006), and disease-free
survival (living vs dead, P = 0.0025). In contrast, ER immunohistochemistry had
significant correlations with the depth of myometrial tumor invasion (P = 0.026)
and disease-free survival (P = 0.032). Multivariate analysis of PR/ER
immunohistochemistry, stage, grade, and myometrial invasion showed that the PR
immunohistochemistry was a significant prognostic factor for survival (P =
0.026). CONCLUSION: PR/ER immunohistochemistry was significantly related to
survival and PR immunohistochemistry appeared to be the most reliable means for
predicting survival in endometrioid adenocarcinoma of the endometrium,
independent of other clinicopathological parameters.
PMID- 9648592
TI - Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory
ovarian cancer: a Gynecologic Oncology Group phase II trial.
AB - OBJECTIVES: In an effort to critically examine the antitumor activity of
altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory
ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the
agent administered in this clinical setting. METHODS: Altretamine was
administered at a dose of 260 mg/m2 orally for 14 days in a 28-day course.
Treatment was continued until disease progression or unacceptable side effects
prevented further therapy. A total of 36 patients (median age: 56.5) were treated
on this trial, of whom 33 were evaluable for toxicity and 30 for response. All
patients had previously received either cisplatin or carboplatin and paclitaxel.
RESULTS: The major side effect was emesis (grade 3-4, 7/33, 21%). The objective
response rate was 10% (one complete response, two partial responses). CONCLUSION:
We conclude that altretamine has limited activity in platinum-refractory ovarian
cancer.
PMID- 9648593
TI - Transforming growth factor-beta 1 induces apoptosis through down-regulation of c
myc gene and overexpression of p27Kip1 protein in cervical carcinoma.
AB - Transforming growth factor-beta 1 (TGF-beta 1) is known to be a potent growth
inhibitor for many cell types, including most epithelial cells. In skin
keratinocytes, TGF-beta 1 has been shown to inhibit growth and to rapidly reduce
c-myc expression. However, the molecular mechanism of TGF-beta 1 action on cell
growth of cervical carcinoma has not yet been elucidated. We thus assessed the
effect of TGF-beta 1 on the growth of cervical carcinoma cell lines. Two cervical
squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying
concentrations of TGF-beta 1, and growth inhibition was evaluated with
tetrazolium-based colorimetric assay. After culture in TGF-beta 1 for 24 h,
inhibition of growth was detected in a dose-dependent manner at concentrations of
0.1-10 ng/ml in both cell lines. This effect of TGF-beta 1 on cultured carcinoma
cells was associated with apoptotic process including oligonucleosomal ladder DNA
and apoptotic body formations. Northern blot analysis revealed c-myc mRNA
expression was suppressed by 10 ng/ml of TGF-beta 1 following 3 h of treatment in
both cell lines. Western blot analysis showed that the level of p27Kip1 protein
was increased after TGF-beta 1 treatment in both cell lines. These results
suggest that the mechanisms by which TGF-beta 1 inhibits the growth of cervical
carcinoma are complex and may include effects on down-regulation of c-myc gene,
and overexpression of p27Kip1 protein.
PMID- 9648594
TI - "Medically necessary" panniculectomy to facilitate gynecologic cancer surgery in
morbidly obese patients.
AB - A retrospective review of patients in our practice who underwent abdominal
panniculectomy to facilitate gynecologic cancer surgery was performed. The
objective of the study was to determine if panniculectomy was a safe and useful
procedure in the morbidly obese gynecologic cancer patient. A total of 12
patients underwent the procedure between 1992 and 1996. Optimal pelvic oncologic
surgery was accomplished in all 12 patients. All aspects of those procedures were
performed by gynecologic oncologists. The Buchwalter retractor was used in all
cases. The patients' weights ranged from 170 to 429 pounds, with a mean of 275
pounds. The mean body mass index was 48, with a range from 37 to 67. Four
patients had a history of diabetes mellitus. Nine patients healed without wound
complications. Three patients developed superficial subcutaneous wound
infections/necrosis that were successfully managed with office debridement.
Abdominal panniculectomy is a reasonably safe procedure that makes radical pelvic
surgery possible regardless of the patient's weight. Prolonged wound bulb suction
drainage may decrease the incidence of wound necrosis/infection in these high
risk patients.
PMID- 9648595
TI - Cervical cancer with paraaortic metastases: significance of residual paraaortic
disease after surgical staging.
AB - Cervical carcinoma frequently metastasizes to the paraaortic region,
necessitating extended field radiotherapy to effect a cure. As imaging modalities
are unreliable in identifying all cases of paraaortic nodal metastases (PAN),
surgical staging is often utilized prior to radiotherapy. This study was aimed at
identifying factors predictive of survival in women with cervical carcinoma and
paraaortic metastases. In particular, survival based on extent of paraaortic
disease was examined. The study group consisted of 43 women (stages IB-IVB)
identified between 1982 and 1993 who were treated with extended field radiation
for cervical carcinoma with histologically confirmed paraaortic metastases. The
estimated 5-year survival for the study population was 24% with a median survival
of 18 months. Pelvic tumor size had a significant impact on survival with the
median survival being 34 months if the primary lesion was < 6 cm compared to 14
months if > or = 6 cm (P = 0.01). Eight of the 26 (31%) women without residual
PAN disease after surgical staging remain alive and disease free (mean follow-up,
74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is
alive 71 months after treatment (P = 0.05). However, a comparison of Kaplan-Meier
survival curves did not show a statistically significant advantage to the
surgical excision of grossly involved PAN (P = 0.98). Although long-term survival
among women with grossly involved, unresected paraaortic metastases is uncommon,
further study is necessary to elucidate the role of surgical excision of bulky
aortic disease in women with cervical cancer.
PMID- 9648596
TI - High serum levels of soluble IL-2 receptor, cytokines, and C reactive protein
correlate with impairment of T cell response in patients with advanced epithelial
ovarian cancer.
AB - The serum levels of interleukin-(IL-)1 alpha, IL-1 beta, IL-2, IL-6, TNF alpha,
and sIL-2R and the proliferative response of peripheral blood mononuclear cells
(PBMC) to phytohemagglutinin (PHA), anti-CD3 monoclonal antibody (mAb),
recombinant IL-2 (rIL-2), and the combination of PHA or anti-CD3 mAb with rIL-2
were studied and correlated with serum levels of C-reactive protein (CRP) in
women with advanced epithelial ovarian cancer. The expression of CD25 and CD122
subunities of membrane-bound IL-2R on PHA- or anti-CD3 mAb-stimulated PBMC was
also studied. In comparisons with the controls, PBMC response to PHA, anti-CD3
mAb, and rIL-2 was significantly lower in the cancer patients. The addition of
exogenous rIL-2 to the PBMC cultures increased response in both controls and
patients but did not modify the significance of the differences. After
stimulation with PHA or anti-CD3 mAb, the percentage of PBMC CD25+ or CD122+ was
significantly lower in patients. The serum levels of IL-1 alpha, IL-1 beta, IL-6,
TNF alpha, sIL-2R, and CRP were significantly increased in patients compared to
the controls. Instead, no differences were observed for serum levels of IL-2. A
strong association was found between high serum levels of the above-mentioned
cytokines, sIL-2R, and CRP. The results of our study on advanced stage (IIIb-IV)
ovarian cancer patients are consistent with the previously reported hypothesis
that high IL-6 and/or CRP serum levels may represent an important and independent
prognostic factor of the likely outcome in cancer patients.
PMID- 9648597
TI - Evidence for a common etiology for endometrial carcinomas and malignant mixed
mullerian tumors.
AB - OBJECTIVE: To elucidate factors linked to the development of malignant mixed
mullerian tumors (MMMT) and determine whether the risk factor profile for these
tumors corresponds with that for the more common endometrial carcinomas. METHODS:
A multicenter case-control study of 424 women diagnosed with endometrial
carcinoma, 29 women diagnosed with MMMT, and 320 community controls was
conducted. Review of pathological reports and slides was performed to classify
cases by histological type. All participants were asked to respond to a
questionnaire which ascertained information on exposure to factors postulated to
be linked to the development of uterine tumors. RESULTS: Women with endometrial
carcinomas and MMMTs were similar with respect to age and educational attainment.
Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas
to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous
estrogen use, and nulliparity were related to risk of both tumor types. Marked
obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of
carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development.
Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold
(95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5).
Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of
carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral
contraceptive use protected against the development of both carcinomas (OR =
0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current
smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34;
95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former
smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not
carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). CONCLUSION: Results from
this study suggest that MMMTs and carcinomas have a similar risk factor profile.
This observation is compatible with the hypothesis that the pathogenesis of these
two histological types of uterine tumors is similar.
PMID- 9648598
TI - Secondary response of ovarian tumors to topotecan treatment.
AB - Three patients presented with ovarian cancer that was initially treated with
paclitaxel and platinum-based compounds. Although responses to these agents
occurred, tumor progression was evident by elevated CA 125 levels after a period
of 11 to 35 months. These patients were then treated with topotecan and exhibited
a response and stopped therapy. All patients subsequently had progression of
disease. The patients were again treated with topotecan and have experienced
favorable responses. All three patients are currently receiving treatment with
topotecan and have stable disease. The results presented here suggest that re
treatment with anti-tumor agents, such as topotecan, may be able to elicit a
response in tumors previously sensitive to these agents.
PMID- 9648599
TI - Ovarian mixed germ cell tumor composed of polyembryoma and immature teratoma.
AB - We report the case of a 41-year-old woman with ovarian mixed germ cell tumor
which was composed of polyembryoma and immature teratoma and who had high serum
levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). By
immunohistochemical methods, AFP was found in yolk sac cells of the embryoid
bodies and immature hepatoid tissues, and hCG was found in giant
syncytiotrophoblastic cells. She was treated with surgery followed by cisplatin
based combination chemotherapy. She is well, and her serum levels of AFP and hCG
have not been elevated for more than 4 years after the treatment.
PMID- 9648600
TI - Cardiac metastasis from carcinoma of the cervix: report of two cases.
AB - BACKGROUND: The presence of cardiac metastasis from cervical carcinoma is
extremely rare. The diagnosis is made almost exclusively postmortem. There are
few cases of premortem diagnosis, and it is believed that when cardiac metastasis
are found in vivo, the prognosis is extremely poor. Due to the rarity of this
condition it is very difficult to standardize care for these patients.
Considering the evidence provided by the cases in this report, it is possible
that aggressive therapy may lengthen patients survival and quality of life. CASE:
We present two cases of cervical carcinoma with metastasis to the heart. Both
patients presented with symptomatology of cardiac tamponade. Both patients had
invasion of the myocardium from presumed endomyocardial metastasis where the
prognosis is even worse. We took an aggressive therapeutic approach to our
patients and had excellent results in one. Our report includes the longest
survival reported for a patient to date with premortem diagnosis of
intramyocardial metastasis from cervical carcinoma. CONCLUSION: We concluded that
the prognosis for cardiac metastasis from cervical carcinoma is extremely poor.
The stage of the disease at initial presentation does not predict the future
development of cardiac metastasis. Taking an aggressive therapeutic approach,
including thoracentesis, chemotherapy, and radiation therapy to the heart,
survival and quality of life can be improved.
PMID- 9648601
TI - Repeat Pap smear at the time of initial colposcopy--another view.
PMID- 9648602
TI - [The effect of an NO-synthase inhibitor, methylene blue, on the function of
certain endocrine glands].
AB - Methylene blue is a thiazine dye, which has been used in the clinical medicine as
disinfection agent and in treatment of methemoglobinemia. The recent
investigations showed that this dye is able to inhibit the activation of
guanylate cyclase pathway in the guanylate cyclase or in the NO-synthase level.
This paper summarizes the experimentally obtained results concerning the
influence of methylene blue on the hypothalamic, hypophyseal, thyroid and
testicular function in rats. The possible mechanism of its influence with
potential role of nitric oxide in the modulation of regulating pathways in these
endocrine glands is discussed.
PMID- 9648603
TI - [Biological effects of interacting shock waves. A modeling study of the effects
of interacting shock waves using erythrocyte hemolysis].
AB - AIM: The effects of high-energy shock wave on tissues were discussed in
literature. The shock wave sources which were used for experiments were developed
for stone fragmentation. The side effects of the applicators are generally low.
Increase of shock wave pressure induce bigger negative pressure amplitude and
this may cause significantly bigger side effects. We used tow shock waves, with
time interval of 5 microseconds. In our opinion, the first shock wave causes
acoustic inhomogenity in shock wave focus and therefore second shock wave acts in
a region with different acoustic parameters. The second shock wave may loss
energy in the focus area by dissipation or absorption. We termed the coupled
shock waves as "interacting shock waves". METHODS AND RESULTS: Hemolysis of
erythrocytes was used for examination of biological toxicity. Shock wave pressure
was 80 MPa, the ratio of positive to negative pressure of single shock waves is
30. For correlation we applied 50 and 100 single shock waves and 50 or 100
couples of two shock waves. Hemolysis after 50 simple shock waves was 4.28 times
lower compared with hemolysis after the same number of coupled shock waves
(interacting shock waves). CONCLUSION: After 50 couples of shock waves hemolysis
is 2.14 times higher compared with 100 single shock waves. This result suggests
that the hypothesis of some interaction existing between two shocks applied in a
very short time interval make future study rightful.
PMID- 9648604
TI - [Voice prostheses mechanisms in total laryngectomy].
AB - Loss of the voice after laryngectomy eliminates to a great extent patient's
social life. Apart from other frequently used methods in laryngectomized
patients, a number of tracheoesophageal vents called voice prostheses, has been
developed in past decade. A survey of their most important features is given. A
basic way of induction of these vents with technique of tracheoesophageal
functions is described.
PMID- 9648605
TI - [Voice rehabilitation with the Provox system after total laryngectomy].
AB - Total laryngectomy has a profound impact on the life of a patient. The loss of
the larynx creates a major communication problem that can result in disruption of
the patients normal pattern of social interaction. It is for this reason that
adaptation to the loss of normal speech has been the focus of research on the
rehabilitation of laryngectomized patients. Tracheoesophageal puncture and
induction of the voice prosthesis have very well results in rehabilitation of the
voice. The long terms clinical results obtained by experience with any of the
complication are described. We use 4 types of voice prosthesis (Provox, Blom
Singer, Bivona Colorado and Czech prosthesis). We have very good experiences with
system Provox. Our collection of the patients with Provox prostheses are 53
patients after total laryngectomy. All tracheoesophageal punctures were done in
second time. Over 85% patients were able to produce satisfying voice. Speech
quality was evaluated by Robe scale. 38.9% of them can speak fluently, which
corresponds with a category F. Local inflammatory reaction occurred in 28.1% that
resulted in extrusion or removal of voice prostheses in 14.2% patients. Use of
voice prostheses in rehabilitation of laryngectomized patients occupies a
significant place.
PMID- 9648606
TI - Erythrocyte sedimentation rate in glass and plastic pipettes.
AB - In the blood collection practice there is a growing number of different closed
systems. They often use plastic pipettes for testing the erythrocyte
sedimentation rate (ESR) according to Westergren. Our previous experience with
plastic pipettes as a part of the system Venoject II suggested that slightly
higher values were obtained when compared to glass pipettes. In order to confirm
these findings a special comparative trial was performed in a group of 302 blood
samples. Statistical evaluation proved a significantly higher sedimentation rate
in plastic pipettes. Based on the values from another group of 132 healthy adults
we try to draw conclusions on the reference interval of ESR in plastic pipettes.
We confirmed that no additional information can be derived from ESR values after
two hours.
PMID- 9648607
TI - [Empathy--understanding through identification].
AB - Empathy is defined as an understanding of another individual through the
projection of ones own personality. It is manifested by the willingness and
effort to perceive, capture and understand the individuals both current and
potential world as exactly as possible with all its subjective meanings and
feelings. It is based on intuition attended by an emotional involvement and
positive interest in the other person. The process of empathy runs in three
stages which overlap: first we enter the other persons subjectivity, than share
in his/her thoughts, emotions and feelings and finally comes the understanding of
the other person. Empathy can be traced to phylogenesis, it is biologically
anchored and in the course of human life (ontogenetic approach) it develops in
the social milieu as do our other abilities. It is one of general effective
factors of psychotherapy and, in the psychotherapeutic relationship, has both a
direct and indirect effect upon the patient (within the hermeneutic process).
Today, this matter is most extensively worked out by the Rogerian and
psychoanalytic psychotherapy.
PMID- 9648608
TI - [Research fraud].
AB - In this article problems of research fraud are discussed. Academic courses of
teaching scientific integrity and the impact of clinical trial fraud on good
clinical research practice are mentioned.
PMID- 9648609
TI - Multiprofessional education in social medicine and clinical ethics.
AB - This contribution describes a project of multiprofessional education in social
medicine and clinical ethics based on educational experience of 3rd Department of
Internal Medicine, First Medical Faculty, Charles University in conjunction with
the Centre of Gerontology Prague. This undergraduate program will be offered to
medics, stomatologists and health science students including the English course
and will invite to participate students from non-medical faculties such as social
science, pedagogy, theology, interested in ethics of health care providing. Basic
principles of the new project are: education in clinical setting, early student
patient contact, multiprofessional education in common seminars of problem based
learning small groups and developing various forms of communication.
PMID- 9648610
TI - [Preparatory courses for applicants for medical studies].
AB - From 1991, the First Medical Faculty of the Charles University arranges for
applicants for the medical study two-semester preparatory courses paid by the
applicants. Their purpose is to improve knowledge of high-school physics,
chemistry and biology with orientation to model questions published by the
faculty [1, 2, 3]. Variants of 100-questions sets for the examination are
generated by a computer and they are altered every year [4]. Two types of
preparatory courses are available. Type A--every Monday and Tuesday between 17.00
and 18.45, physics and chemistry in odd weeks, biology and Latin in even weeks.
Latin is not a discipline considered during the admission examination, however,
managing of its basic knowledge facilitates not only understanding problems
considered in the other disciplines, but it is particularly useful for learning
the special terminology in the first year of the study of medicine. Course of
type B is held once a month, on Saturdays between 8.30 and 14.00 and it is
particularly designed for applicants residing beyond the capital city of Prague.
In the course of 10 semesters implemented, 980 and 1,410 students passed through
courses of type A and B, respectively [5, 6]. The purpose of our analysis was to
evaluate the difference between results of admission procedure of applicants who
participated and of those who did not participate in the preparatory course.
Basic data were yielded by the Department of Students of the Deans Office. We
considered the number of applicants, their results in the course of their four
years of study at high schools and the number of points acquired in physical,
chemical and biological tests. We furthermore obtained applications for
preparatory courses in school years 1993/94 and 1994/95. The results were
processed with the help of data base programs Access and Excel (Microsoft). In
each of the years of interest, the applicants were divided into four groups
depending on the type of the study: 1--medicine (L) and 2--stomatology (S) or
depending on whether 3--they were registered in preparatory courses or 4--not.
The analysis carried out resulted in the following conclusion: a--both groups of
applicants (registered and not registered in preparatory courses) had comparable
study results during the last four years of their high-school study; b--in the
admission procedure, students, who passed through preparatory courses, achieved
undoubtedly better results in comparison with those who did not pass through
these course, which holds in medicine as well as stomatology; c--there was about
the same improvement of knowledge of physics, chemistry and biology in both types
of the preparatory courses.
PMID- 9648611
TI - [The Prague school of anatomy and its illustrators].
AB - The centennial commemorial of the birthday of Ladislav Borovansky gives us an
incentive for describing a short history of Czech anatomy in Medical Faculty of
Charles University with their textbooks and painters. Parallelly with them are
presented some other distinguished painters active in anatomical aspect of
illustration.
PMID- 9648612
TI - [75 years' of the 2nd Clinic of Gynecology and Obstetrics of the 1st Medical
School of Charles University and the General Medical School Hospital in Prague on
the 120th anniversary of the opening of the Zemske Maternity Hospital].
PMID- 9648613
TI - [Activity of the 2nd Clinic of Gynecology and Obstetrics from its founding to the
end of World War II (1920-1945)].
AB - History of the IInd Gynaecological and Obstetric Clinic of 1st Faculty of
Medicine, Charles University in Prague is recorded here from its establishment in
1920 to the end of World War II. The activities of the Clinic are depicted in
characterization of prominent personalities who worked here in this period. The
characterization is focussed mostly on head physicians and their clinical,
pedagogical and scientific activities and their works published.
PMID- 9648614
TI - [Recent history of the 2d Gynecology-Obstetrical Clinic of the 1st Medical School
of Charles University (1945-1995)].
AB - In 1995 75 years had elapsed since the time when the decision to found the Second
Department of Obstetrics and Gynaecology was made by the Medical Faculty. An
Institution arose which trained a great many qualified medical workers, midwives,
students, and specialist obstetricians-gynaecologists. In the present article we
should like to remember the teachers who have taken over the style of work from
their predecessors and educated their pupils in the love and devotion to their
discipline. In the last 50 years five Heads of the Department worked in the
Second Department of Gynaecology and Obstetrics. Each of them made part of the
history of the Department and imprinted there his or her characteristic image.
Our wish is to acquaint you with the message of the predecessors as well as with
the contemporary history and development of the Department in the field of
education, research, and therapeutics.
PMID- 9648615
TI - [Present status of the 2nd Gynecology-Obstetrical Clinic of the 1st Medical
School of Charles University and the General Medical School Hospital in Prague].
PMID- 9648616
TI - Jens Christian Skou awarded the Nobel prize in chemistry for the identification
of the Na+, K(+)-pump.
PMID- 9648617
TI - Potentiation of the contraction following a prolonged depolarization in isolated
ferret myocardium.
AB - The contractile force was studied in ferret papillary muscles during voltage
clamp depolarizations, using the single sucrose gap method. Prolongation of a
test depolarization within a train produced potentiation of the following
contraction. The effects of varied duration and membrane potential of the test
depolarization upon the potentiated force of the following beat were studied. We
assumed that force of a beat was an index of calcium entry on the previous
depolarization. The relationship between the peak contractile force of the
following potentiated beat and the systolic membrane potential of the test
depolarization revealed an equilibrium around -18 mV. This was manifest after 100
ms of no effect. Positive potentials caused potentiation of force of the
following beat; negative potentials caused suppression of force of the following
beat. Calcium entry, if carried by an electrogenic exchange mechanism, would be
revealed as a membrane current developing after 100 ms. Membrane current at these
times was always outward. When the duration of the test depolarization was
prolonged, outward current prior to repolarisation progressively increased. When
the duration of the test depolarization was held constant, outward current was
varied by variation in membrane potential. Force of the following beat was
proportional to the test clamp membrane potential. The potentiation of the
contraction following a prolonged depolarization was abolished by substituting
75% of the sodium in the perfusion medium with lithium. These results are
compatible with the hypothesis that potentiation of force following a prolonged
depolarization is derived from calcium entry into myocardial cells by reversed
sodium-calcium exchange.
PMID- 9648618
TI - Effects of endurance training on the size and blood flow of the arterial
conductance vessels in humans.
AB - The aim of the present study was to determine non-invasively the effects of
endurance training on both the size and blood flow of the arterial conductance
vessels during exercise by men. Twelve healthy male subjects were assigned to
either an exercise-trained group (ET, n = 7) or a sedentary control group (S, n =
5). The ET group underwent cycle-endurance training for 8 weeks (80% VO2max, 40
min day-1, 5 days week-1). The S group led normal lives during the 8-week period.
Before and after the training period, cross-sectional areas (CSA) of the
ascending and abdominal aorta were measured by echography. Measurements were
taken in the semisupine position on a cycle ergometer fitted with a backrest, at
rest and during 40, 60 and 80% VO2max of exercise. In addition, Doppler
ultrasonographic velocity and flow in the ascending aorta were simultaneously
measured. The CSA of the ascending and abdominal aorta after training were
significantly larger than those before training in the ET group. Although there
were no significant differences in the peak and mean velocities in the ascending
aorta before and after the training in the ET group, the blood flow in the
ascending aorta during exercise after training was significantly larger than that
found before training at each relative intensity. There were no significant
differences in any of the Doppler echographic parameters in the S group. These
findings suggest that the arterial conductance vessels can be morphologically
altered in an adaptive response to the endurance training. Furthermore, the
dilation of the conductance vessels with endurance training contributes to an
increase in blood flow to the exercising muscles without a rise in blood
velocity. In other words, the arterial conductance vessels adapt to maintain
adequate blood velocity and shear stress.
PMID- 9648619
TI - Analysis of blood pressure responses during exercise by logistic function curve
in hypertension: effects of age, gender and physical training.
AB - During exercise blood pressure fluctuates from minute to minute and does not rise
linearly with time. Blood pressure responses were evaluated during exercise by a
logistic function curve. Thirty-nine hypertensive patients underwent exercise
testing with an ergometer, employing a multistage method (25 watts increment,
every 3 min). We plotted the exercise duration on the X-coordinate and systolic
blood pressure on the Y-coordinate and blood pressure was assumed to form a
logistic curve for exercise duration. The relationship of systolic blood pressure
vs. exercise duration was better fitted into a logistic function curve than a
linear regression model. The logistic curve was defined by lower plateau, upper
plateau, SPX (the X-coordinate at the shift point) and df (SPX), the maximal
slope at the shift point. The effects of aging, gender and physical training were
then analyzed on the curve. Aging did not affect lower plateau, upper plateau and
SPX but augmented df (SPX), indicating greater blood pressure responses in older
subjects during exercise. In females the curve was shifted to the left compared
to males (SPX: 4.9 vs. 8.3 min, P < 0.05) without changes in plateaux and df
(SPX), indicating greater blood pressure responses than males. Physical training
for 3 weeks decreased the lower plateau from 157 to 144 mmHg (P < 0.05) and
shifted the curve to the right (SPX: 7.1 vs. 8.6 min, P < 0.05), indicating
unchanged blood pressure responses after training because of the opposite effects
by decreases in the lower plateau vs. the curve shift to the right. In
conclusion, blood pressure during exercise is better delineated by a logistic
function curve than a linear regression model. The biological or physiological
significance of df (SPX) is not clear at present and needs further
investigations.
PMID- 9648620
TI - Effects of red blood cell hyperaggregation on the rat microcirculation blood
flow.
AB - This study presents the effects of red blood cell (RBC) hyperaggregation on the
blood flow and pressure in the rat mesentery and cremaster network. We
exclusively studied in situ non-vasodilated organs, in order to maintain the
physiological regulation mechanisms. Dextran 500 was injected at different
concentrations to increase RBC aggregation. The aggregation rate was measured on
very small blood samples with an erythroaggregameter (SEFAM) which evaluated the
disaggregating shear stress (tau D) needed to break the RBC aggregates.
Microscopic observations and laser Doppler velocimetry were used to quantify the
flow rate. The plasmatic dextran concentration (C) increase had different
correlated effects: for example, tau D increased from 3 dynes cm-2 (for the
control sample) to 14 dynes cm-2 (for C = 75 microM L-1); the flow rate was
reduced threefold and very large aggregates were observed in the venules; the
arteriolar pressure increased while venular pressure decreased. In order to
differentiate the effects of RBC hyperaggregation from those of plasma
hyperviscosity (due to dextran 500) on microcirculatory blood flow, we injected
an RBC antiaggregating drug (troxerutine) (50 or 100 mg kg-1 i.v.). The
consequences were a high reduction for (tau D) (from 14 dynes cm(-2)-9 dynes cm
2), smaller aggregates and higher blood flow in the venules. No effect of
troxerutine was observed on plasma viscosity (plasma control: 1.9 cP with or
without troxerutine; plasma with dextran at C = 75 microM L-1: 2.45 cP with or
without troxerutine). The results strongly suggest that RBC aggregation has a
significant influence on blood flow rate in the microcirculatory network.
PMID- 9648621
TI - Effects of age and gender on shortening velocity and myosin isoforms in single
rat muscle fibres.
AB - The maximum velocity of unloaded shortening (V0) and the myosin heavy chain
(MyHC) and light chain (MyLC) isoform composition were determined in single
fibres from soleus and extensor digitorum longus (EDL) muscles of male and female
rate 3-6 and 22-24 months old. In the soleus muscle, the beta/slow (type I MyHC)
isoform predominated in both young and old animals, irrespective of gender. In
the EDL, fibres expressing type IIX MyHC or a combination of IIX and IIB (IIXB)
MyHC isoforms were predominant in old rats, while type IIB MyHC fibres
predominated in young individuals of both genders. The V0 of soleus fibres
expressing the type I MyHC isoform decreased (P < 0.001) by 40% with age in spite
of an unchanged MyLC composition. In the EDL, the V0 of fibres expressing IIX,
IIXB and IIB MyHC isoforms did not changes with age or differ between males and
females. In conclusion, similar age-related changes in V0 and MyHC composition
were observed in single muscle cells from both male and female rats. The present
results demonstrate that the relationship between V0 and MyHC isoform composition
at the single fibre level is similar in male and female rats, and that similar
qualitative changes take place during ageing in both genders.
PMID- 9648622
TI - Influence of cold shivering on fine motor control in the upper limb.
AB - The aim of the investigation was to determine the effects of cold shivering on
the accuracy of force output in distal, middle and proximal muscles of the upper
limb. Test of hand grip strength, elbow flexion and shoulder flexion (each done
at 10% maximal voluntary contraction for 15 s) were done under three conditions:
(1) thermoneutral air (27 degrees C), a condition of thermal comfort; (2) cold
air (10 degrees C), a condition eliciting an increase in tonic muscle activity;
(3) and cold air (10 degrees C) with a cold drink (8 degrees C), a condition that
causes visible shivering. The averaged (root mean square) electromyogram (AEMG)
and mean power frequency (MPF) were measured from proximal, middle and distal arm
muscles during the tests and compared. The control of force output was highly
effective at thermoneutral condition for all motor tasks. During the cold air
condition, all muscles were tonically active but there was no effect on accuracy
of test performance. However, AEMG increased approximately 20% (P < 0.05) with
respect to test performance in thermoneutral condition. During the cold air/cold
drink condition, all muscles were shivering to a different extend. AEMG during
test performance increased 30-150% in comparison to thermoneutral condition (P <
0.05). In this case, hand grip and elbow flexion were not adversely affected
(these tests require middle and distal muscles) by cold shivering. However, the
accuracy of performance of shoulder flexion was adversely affected. This is
consistent with the fact that proximal muscles are more active during cold
shivering.
PMID- 9648623
TI - Effects of noradrenaline and flow on lactate uptake in the perfused rat hindlimb.
AB - Skeletal muscle can release or take up lactate depending on the lactate
concentration gradient across the cell membrane. In the perfused rat hindlimb
without arterial lactate, both noradrenaline (NA) infusion and increased flow
promote lactate release and oxygen consumption (VO2). However, it is unclear
whether NA or increased flow rate have similar effects on lactate uptake. The
present study compares these effects in the rat hindlimb perfused at a basal flow
rate of 0.33 mL min-1 g-1 and 25 degrees C in the presence of added arterial
lactate. When 10 mmol L-1 L-(+)-lactate was added to the arterial perfusate,
lactate was taken up (16 +/- 1.0 mumol g-1 h-1, n = 13) by the hindlimb with a
35% higher VO2 than that without added lactate. Doubling perfusion flow rate
enhanced lactate uptake and VO2 by 120% and 40%, respectively. Glucose uptake was
also increased (by 253%) with increased flow. Infusion of NA increased perfusion
pressure, VO2 and glucose uptake similarly to those induced by increased flow
rate. However, lactate uptake was inhibited by NA. This inhibition was not
altered by the beta-adrenergic antagonist propranolol. Vasopressin also showed
similar effects to NA to decrease lactate uptake associated with increased VO2
and vasoconstriction. These data indicate that in the presence of a high arterial
lactate concentration, NA has opposite effects from increased flow rate on
skeletal muscle lactate uptake although both have similar effects on lactate
release in the absence of arterial lactate. Inhibition of lactate uptake may
relate to the vasoconstrictive action of NA.
PMID- 9648624
TI - Inheritance of static and dynamic arm strength and some of its determinants.
AB - Maximal static, eccentric and concentric torques and arm components estimated by
anthropometry and measured by computed tomography were evaluated in 25 male
monozygotic twins and 16 dizygotic twins (22.4 +/- 3.7 years). The importance of
genetic and environmental factors in the observed variation in these measurements
was estimated by genetic model-fitting techniques. In this sample of young adult
male twins, genetic factors were significant in most of the strength
measurements, arm muscle components and muscle activation variables. The
contribution of genetic factors in strength measures depended on the angle,
contraction type and to some extent on contraction velocity. For isometric
strength, angle-specificity in genetic and environmental variation could be
attributed to the degree of variability in muscle activation and performance
discomfort at each specific angle, with the highest unique environmental impact
at extreme angles. The high genetic contribution at 170 degrees, but not at 50
degrees, possibly expressed different contributions of genetic factors in the
muscle-length factor and moment arm in torques at both angles. The importance of
genetic factors in eccentric arm flexor strength (62-82%) was larger than for
concentric flexion (29-65%), as the pattern of genetic determination followed the
torque-velocity curve. Genetic variations in contractile and elastic components,
contributing differently to eccentric and concentric torques, together with
velocity-dependent actin-myosin binding factors, could account for the observed
differences. The broad heritability was very high for all anthropometric and arm
cross-sectional area measurements (> 85%) and common environmental factors were
only significant for anthropometrically estimated mid-arm muscle tissue are
(48%). Heritability estimates of different arm muscularity measurements were
comparable.
PMID- 9648625
TI - Capsaicin can abolish spontaneous tone in guinea-pig trachealis.
AB - The properties of spontaneous tone in isolated preparations of guinea-pig
tracheal smooth muscle were examined. Experiments with control preparations
revealed that 5-15 min after stretching the muscle with 0.15 mN, the spontaneous
tone assumed a plateau value from which it declined gradually during the
following hour. During the plateau, the force amounted to approximately 35% and 1
h later to approximately 20% of a maximum KC1 contraction. The tone was
independent of tetrodotoxin, atropine and propranolol. Indomethacin quickly and
completely relaxed the tone in 15 of 21 preparations. However, four preparations
retained some tone even after 1 h of treatment. Exposure to the C-fibre
influencing drug capsaicin resulted in a dose-dependent, reversible suppression
of spontaneous tone, normally preceded by a transient increase in force. No
spontaneous tone at all remained after 1 h of 10 microM capsaicin. This effect
was also found in preparations pretreated with tetrodotoxin, atropine and
propranolol. Preparations, deprived of spontaneous tone by capsaicin-treatment,
contracted distinctly when exposed to 10 microM arachidonic acid. This
contraction was almost completely abolished by indomethacin, which indicates that
the prostaglandin synthesis is functioning after capsaicin treatment and, thus,
that inhibition of this synthesis is not responsible for the capsaicin effect.
Exposure to phosphoramidon increased the spontaneous tone almost threefold.
Addition of 3 nM neurokinin A in the permanent presence of capsaicin gave weaker
contractions in preparations where prostaglandin synthesis had been abolished by
indomethacin, as compared to contractions in preparations with intact
prostaglandin synthesis. The data indicate that a continuous release of
tachykinins from sensory C-fibres is essential for the generation of spontaneous
tone and that a combination of tachykinins and prostaglandins determine the size
of the tone in this preparation.
PMID- 9648626
TI - Glomerular charge selectivity for horseradish peroxidase and albumin at low and
normal ionic strengths.
AB - The classical concept of a negative glomerular charge barrier has recently been
questioned, mainly based on the somewhat high clearance for anionic horseradish
peroxidase (HRP). The validity of using anionic HRP can be tested by changing the
properties of the charge barrier. A rather unequivocal approach is to reduce the
ionic composition of the perfusate and hence increase the Debye length. We
determined the glomerular clearance for horseradish peroxidase and serum albumin,
using isolated rat kidneys perfused at 8 degrees C to reduce the tubular
modification of the primary urine. The perfusate contained trace amounts of the
neutral 125I-nHRP and the anionic 131I-aHRP and were otherwise identical except
for different ionic strengths, 152 mM and 34 mM, respectively. During control,
the fractional clearance (theta) was 0.11 +/- 0.015 for nHRP and 0.045 +/- 0.010
for aHRP, with an average clearance ratio (n/a) of 2.8 +/- 0.24. Low ionic
strength reduced theta for aHRP to 0.027 +/- 0.006, giving an increased clearance
ratio for HRP of 4.2 +/- 0.44. The existence of a negative charge barrier is
supported by the experiments. The result obtained during normal perfusion is
compatible with a charge density (omega) of 34 mEq L-1, using a model of
homogeneously charged membrane. Low ionic strength perfusion reversibly reduced
the concentration of fixed charges to 12 mEq L-1, suggesting an almost threefold
increase of the glomerular membrane volume. Thus, the glomerular charge barrier
should be regarded to have a dynamic gel structure rather than being a rigid
membrane.
PMID- 9648627
TI - Effects of receptor blockade on metabolism and renal actions of vasopressin in
conscious dogs.
AB - Vasopressin--but not the V2 receptor agonist [deamino-cis1,D-Arg8]-vasopressin
(dDAVP)--may mediate natriuresis in dogs. The present study investigated this
phenomenon by use of nonpeptide antagonists to V1a and V2 receptors 1-?1-[4-(3
acetylaminopropoxy)benzoyl]-4-piperidyl?-3,4-dihydro-2 (1H)-quinolinone (OPC
21268) and 5-dimethylamino-1-?4-(2-methylbenzoylamino)-benzoyl?-2,3,4,5-tetra
hydro-1 H-benzazepine (OPC-31260), respectively) hypothesising that only V1a
inhibition would reduce the natriuresis. In conscious dogs vasopressin secretion
was suppressed by water loading (2% body weight) and replaced by infusion of
vasopressin (50 pg min-1 kg-1) resulting in physiological plasma concentrations
(plasma levels of AVP (pAVP) = 2.0 +/- 0.1 pg mL-1). In this setting, OPC-21268
did not change the rate of sodium excretion. OPC-31260 increased water excretion
12-fold without significant changes in sodium excretion. Heart rate, mean
arterial blood pressure, glomerular filtration rate, and clearance of endogenous
Li+ were unchanged. During vasopressin infusion, both antagonists increased pAVP,
OPC-21268 by 20% and OPC-31260 by 100% (2.0 +/- 0.2-4.0 +/- 0.3 pg mL-1). In the
absence of vasopressin infusion, OPC-31260 did not increase pAVP. Thus, the
increase in pAVP appeared to be due to a decrease in metabolic clearance rate.
The results indicate that the present dose of V1a receptor inhibitor OPC-21268
does not reduce sodium excretion and that both vasopressin antagonists inhibit
vasopressin metabolism.
PMID- 9648629
TI - Regulation of porcine biliary secretion by secretin.
AB - The importance of physiological plasma levels of secretin in biliary bicarbonate
secretion is not known. However, in anaesthetized pigs the substantial hepatic
output of bicarbonate into the duodenum in response to low doses of secretin
exceeds pancreatic bicarbonate output. The aim was therefore to study the
relationship between duodenal acidification, secretin and hepatic biliary
bicarbonate output in the conscious pig. Gottingen minipigs (n = 22) were
cholecystectomized and the common bile duct catheterized. The biliary bicarbonate
secretion in response to intraduodenal HCl, secretin or pentagastrin given
intravenously, and to meal was studied. Intraduodenal HCl infusion, secretin and
pentagastrin given intravenously augmented hepatic bicarbonate output and plasma
secretin concentrations significantly. The secretin response to acidification was
sufficient to explain the subsequent increase in biliary bicarbonate secretion.
Hepatic bicarbonate secretion and concentrations of CCK and secretin in plasma
increased postprandially. Exclusion of bile salts from the duodenum abolished
postprandial increase in bile volume and increased release of CCK in fasting and
fed pigs whereas secretin release was diminished. The results demonstrate that
hepatic bicarbonate secretion is stimulated by endogenous secretin and therefore
may have a physiological role in duodenal neutralization.
PMID- 9648628
TI - A2 adenosine receptors in Mongolian gerbil middle ear epithelium and their
regulation of Cl- secretion.
AB - The present study investigates the effects of adenosine and its analogues on Cl-
secretion in primary cultures of gerbil middle ear epithelium. Short-circuit
current (Isc), an index of transepithelial active transport, was measured on the
same cells cultured on porous filters. Baseline Isc and transepithelial
resistance were 27.0 +/- 0.7 microA cm-2 and 275 +/- 7 omega cm2, respectively (n
= 178). Extracellular adenosine and its analogues elicited a sustained increase
in Isc when added to apical or basolateral surfaces. Both the A2A selective
agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine and
the A2A/A2B nonselective agonist 5'-(N-ethyl-carboxamido)adenosine (NECA)
increased Isc, but NECA was more effective than CGS21680. A1 selective antagonist
8-cyclopentyl-1,3-dipropylxanthine did not reduce NECA-induced Isc. These results
suggest the presence of both A2A and A2B receptors. NECA did not stimulate a rise
in the intracellular Ca2+ concentration ([Ca2+]i) in single middle ear epithelial
cells cultured on glass coverslips. Dibutyryl cAMP (dbcAMP) induced an initial
transient increase in Isc followed by the sustained plateau. Addition of dbcAMP
also caused a transient increase in [Ca2+]i. The protein kinase A inhibitor, N-[2
(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, greatly reduced the
increase in the Isc responses to NECA. 1,2-Bis-(2-aminophenoxy)ethane N,N,N',N'
tetraacetic acid-acetoxymethyl ester influenced neither the NECA-induced increase
in Isc nor the dbcAMP-induced sustained phase of Isc, but greatly inhibited the
dbcAMP-induced transient increase in Isc. Glibenclamide, a cystic fibrosis
transmembrane conductance regulator (CFTR) channel inhibitor, reduced the NECA
induced Isc. These results indicate that extracellular adenosine and its
analogues activate the cAMP-protein kinase A system, but not intracellular Ca(2+)
dependent mechanisms, leading to Cl- secretion, possibly through the CFTR Cl-
channels in the cultured gerbil middle ear epithelium.
PMID- 9648630
TI - Appearance of contractile endothelin-B receptors in rat mesenteric arterial
segments following organ culture.
AB - The aim of this study was to examine how different procedures for organ culture
affect the expression of contractile endothelin(ET)-B receptors in a branch of
the rat mesenteric artery. In fresh segments, ET-1 and ET-3 induced similar
strong contractions, ET-1 being 20-fold more potent, whereas neither of the
selective ETB receptor agonists, sarafotoxin 6c (S6c) nor IRL 1620, induced
significant contractions. In segments cultured for 1 day, ET-3 was only 3-fold
less potent as ET-1, and S6c and IRL 1620 induced concentration-dependent
contractions which were about 60% of the ET-1 induced contraction. The maximum
contractile response to S6c was not altered in segments cultured with foetal calf
serum or in buffer solution, but was reduced to about 20% of the control value
when cultured in glucose-free buffer solution. The contraction to S6c was
abolished in segments placed in cold (4 degrees C) buffer solution. Removal of
the endothelium had no effect on the S6c-induced contractions. Arteries cultured
at isometric tension (at 2 mN) for 1 day achieved the same contractile response
for ETB agonists as resting segments. Pressurized arteries (60 mmHg) did not
constrict to S6c when mounted as a fresh segment but demonstrated a strong
contraction after 1 day at this transmural pressure. This study suggests that the
appearance of ETB receptor mediated contraction following organ culture is not
dependent on specific nutrients, endothelial factors or absence of intrinsic
tension, but is a metabolically active process.
PMID- 9648632
TI - Intracellular calcium and electrical restitution in mammalian cardiac cells.
AB - The role of calcium current and changes in intracellular calcium concentration
([Ca2+]i) in regulation of action potential duration (APD) during electrical
restitution process was studied in mammalian ventricular preparations. Properly
timed action potentials were recorded from multicellular preparations and
isolated cardiomyocytes using conventional microelectrodes and EGTA-containing
patch pipettes. APD increased monotonically in canine and guinea pig ventricular
preparations with increasing diastolic interval (DI), while in rabbit papillary
muscles the restitution process was biphasic: APD first lengthened, then
shortened as the DI increased. When the restitution process was studied in single
cardiomyocytes using EGTA-containing patch pipettes, the restitution pattern was
similar in the three species studied. Similarly, no difference was observed in
the recovery time constant of calcium current (/Ca-L) measured under these
conditions in voltage clamped myocytes. Loading the myocytes with the [Ca2+]i
chelator BAPTA-AM had adverse effects in rabbit and canine cells. In rabbit
myocytes steady-state APD lengthened and the late shortening component of
restitution was abolished in BAPTA-loaded cells. In canine myocytes BAPTA-load
shortened steady-state APD markedly, and during restitution, APD decreased with
increasing DI. The late shortening component of restitution, observed in
untreated rabbit preparations, was greatly reduced after nifedipine treatment,
but remained preserved in the presence of 4-aminopyridine or nicorandil. Beat to
beat changes in APD, peak/Ca-L and [Ca2+]i, measured using the fluorescent dye,
Fura-2, were monitored in rabbit ventricular myocytes after a 1-min period of
rest. In these cells, the shortening of APD was accompanied by a gradual
reduction of the peak/Ca-L and elevation of diastolic [Ca2+]i during the initial
eight post-rest action potentials. It is concluded that elevation of [Ca2+]i
shortens, while reduction of [Ca2+]i lengthens APD in rabbit, but not in canine
ventricular myocytes. These differences may probably be related to different
distributions of [Ca2+]i-dependent ion currents and/or to differences in calcium
handling between the two species.
PMID- 9648631
TI - The novel non-peptide selective endothelin A receptor antagonist LU 135,252
protects against myocardial ischaemic and reperfusion injury in the pig.
AB - The aim of the study was to investigate the efficacy of the novel non-peptide
selective endothelin A (ETA) receptor antagonist LU 135,252 to limit the extent
of myocardial ischaemic and reperfusion injury. Administration of LU 135,252 (1
and 5 mg kg-1 i.v.) to anaesthetised pigs reduced mean arterial pressure (MAP)
from 91 +/- 4 to 79 +/- 3 mmHg (P < 0.05) and 96 +/- 3-82 +/- 3 mmHg (P < 0.01),
respectively. Heart rate, coronary blood flow and coronary vascular resistance
were not affected by LU 135,252. The infarct size induced by 45-min ligation of
the left anterior descending coronary artery (LAD) followed by 4-h reperfusion in
pigs was 81 +/- 5% of the area at risk in control animals given vehicle (n = 8).
In pigs receiving 1 mg kg-1 (n = 6) or 5 mg kg-1 (n = 8) of LU 135,252 i.v. 20
min before ischaemia the infarct size was reduced to 64 +/- 3% (P < 0.05) and 35
+/- 4% (P < 0.001), respectively, of the area at risk. During the reperfusion
period there was a non-significant trend towards a higher coronary blood flow and
a lower coronary vascular resistance in the groups given LU 135,252 compared to
controls. Myocardial overflow of ET-like immunoreactivity was increased during
the reperfusion period but it was not affected by administration of LU 135,252.
It is concluded that administration of the selective ETA receptor antagonist LU
135,252 effectively protects the myocardium from ischaemia/reperfusion injury,
indicating that the ETA receptor subtype is involved in the development of
ischaemia/reperfusion injury.
PMID- 9648633
TI - Blood flow in the peritendinous space of the human Achilles tendon during
exercise.
AB - This study evaluated blood flow in the peritendinous space of the human Achilles
tendon during rest and 40-min dynamical contraction of m. triceps surae. In 10
healthy volunteers 133Xe was injected in to the peritendinous space just
ventrally to the Achilles tendon 2 and 5 cm proximal to the calcaneal insertion
of the tendon, respectively. Blood flow 5 cm proximal to the Achilles tendon
insertion was found to increase 4-fold from rest to exercise whereas the exercise
induced increase in blood flow was less pronounced, only 2.5-fold, when measured
2 cm proximal to the Achilles tendon insertion. Lymph drainage from the area was
found to be negligible both during rest and exercise. We conclude that dynamical
calf muscle contractions result in increased peritendinous blood flow at the
Achilles tendon in humans.
PMID- 9648634
TI - Internal jugular venous spillover of noradrenaline and metabolites and their
association with sympathetic nervous activity.
AB - It is recognized that the brain plays a pivotal role in the maintenance of blood
pressure and the control of myocardial function. By combining direct sampling of
internal jugular venous blood with a noradrenaline isotope dilution method, for
examining neuronal transmitter release, and microneurographic nerve recording, we
were able to quantify the release of central nervous system noradrenaline and its
metabolites and investigate their association with efferent sympathetic nervous
outflow in healthy subjects and patients with pure autonomic failure. To further
investigate the relationship between brain noradrenaline, sympathetic nervous
activity and blood pressure regulation we examined brain catecholamine turnover,
based on the internal jugular venous overflow of noradrenaline and its principal
central nervous system metabolites, in response to a variety of pharmacological
challenges. A substantial increase was seen in brain noradrenaline turnover
following trimethaphan, presumably resulting from a compensatory response in
sympathoexcitatory forebrain noradrenergic neurones in the face of interruption
of sympathetic neural traffic and reduction in arterial blood pressure. In
contrast, reduction in central nervous system noradrenaline turnover accompanied
the blood pressure fall produced by intravenous clonidine administration, thus
representing the blood pressure lowering action of the drug. Following
vasodilatation elicited by intravenous adrenaline infusion, brain noradrenaline
turnover increased in parallel with elevation in muscle sympathetic nervous
activity. While it is difficult to assess the source of the noradrenaline and
metabolites determined in our studies, available evidence implicates
noradrenergic cell groups of the posterolateral hypothalamus, amygdala, the A5
region and the locus coeruleus as being involved in the regulation of sympathetic
outflow and autonomic cardiovascular control.
PMID- 9648635
TI - Platelet serotonin transporter density and related parameters in endurance
trained and sedentary male subjects.
AB - A number of peripheral indices of serotonergic function were examined in
endurance-trained (ET) and sedentary males using the blood platelet as a model of
the serotonergic neurone. The aim of the study was to investigate possible
involvement and adaptation of the central serotonergic system in exercise-induced
fatigue. The [3H] paroxetine-defined density of platelet serotonin transporters,
platelet serotonin content and the plasma concentration of amino acids were
determined in 10 ET and eight sedentary males. The mean (standard deviation)
density of the serotonin transporter in the platelet membranes of the ET subjects
was greater [1237 (182) fmol mg protein-1] than that of the sedentary subjects
[910 (119) fmol mg protein-1; P = 0.013]. No difference (P = 0.51) could be seen
between the median (range) platelet serotonin content of the ET subjects [0.98
(0.37-3.04) nmol platelet-10] and that of the sedentary subjects [0.82 (0.18
1.49) nmol platelet-10]. The platelet poor plasma concentrations of tryptophan
and tyrosine were lower in the ET subjects (P = 0.028 and 0.015, respectively).
The present study suggests that the platelet membrane of the ET subjects has a
greater density of the serotonin transporter and that this is inversely related
to the circulating concentration of the serotonin precursor, tryptophan. It
remains to be resolved whether the increase in serotonin transporter density in
the platelet membrane of ET subjects is reflected centrally and whether the ET
platelet population may be sufficiently different from that of sedentary
individuals to alter serotonin transporter density.
PMID- 9648636
TI - Myocardial interstitial noradrenaline monitoring during occlusion of inferior
vena cava in cats.
AB - To investigate myocardial interstitial noradrenaline (NA) kinetics during
activation of systemic sympathetic nerves, we applied a dialysis technique to the
left ventricle of anaesthetised cats and monitored myocardial interstitial NA
levels during 6-min occlusion of the inferior vena cava (IVC). Dialysis probes
were implanted in the left ventricular wall, and dialysate NA levels as an index
of myocardial interstitial NA levels, were measured with high-performance liquid
chromatographic-electrochemical detection. During IVC occlusion, dialysate NA
levels progressively increased from 110 +/- 17 pmol L-1 in the control and
reached 620 +/- 160 pmol L-1 at 4-6 min of IVC occlusion. Local administration of
omega-conotoxin GVIA at 10 microM decreased the control dialysate NA level to 35
+/- 0.2 pmol L-1. The IVC occlusion induced increase in dialysate NA was
suppressed only at 0-2 min of IVC occlusion. Intravenous injection of omega
conotoxin GVIA (10 micrograms kg-1) did not increase the dialysate NA levels
during IVC occlusion. Local administration of desipramine at 100 microM increased
the control dialysate NA level to 900 +/- 73 pmol L-1. The IVC occlusion induced
progressive increase in dialysate NA was augmented at 2-6 min of IVC occlusion.
These results suggest that the early increase in myocardial interstitial NA
levels is mainly caused by neuronal release of NA from cardiac sympathetic nerve
terminals, and that extraction from the circulation and neuronal NA uptake
contribute to changes in myocardial interstitial NA levels after a delay of
several minutes.
PMID- 9648637
TI - Modulation of short latency stretch reflexes during human hopping.
AB - To gain insight into central and peripheral reflex control mechanisms in moving
humans we have investigated short latency stretch reflex activity in m. triceps
surae during two legged hopping. The objectives were: (1) to compare movement
induced short latency stretch reflexes in soleus and medial gastrocnemius (MG)
muscles, (2) to determine the relationship between the size of these reflexes and
the muscle spindle stretch velocities, and (3) to compare the size of the
movement induced short latency stretch reflexes and the H-reflexes
simultaneously. Six well-trained healthy male subjects participated and they
hopped at three different work rates. Surface electromyogram (EMG) and H-reflexes
were recorded during hopping. Muscle spindle length changes were estimated as the
difference between estimated origin-to-insertion length changes and tendon length
changes. The important findings were that during hopping: (1) movement induced
short latency stretch reflexes were observed consistently in soleus, (2) the EMG
amplitude of this stretch reflex was negatively correlated with the estimated
peak muscle spindle stretch velocity (rs = -0.52, P < 0.02), and (3) the
amplitude of the soleus H-reflex at touchdown did not change in parallel with the
stretch reflex. The negative correlation observed between the stretch reflex and
the estimated peak muscle spindle stretch velocity in soleus is opposite to the
basic velocity sensitive behaviour of stretch reflexes mechanically elicited
during resting conditions. Possible control mechanisms are discussed.
Additionally, muscle spindle length changes estimated from changes in the
skeletal movements (joint angles) should be inferred cautiously because of tendon
compliance, especially at high tendon forces.
PMID- 9648638
TI - Serotonin and neuroendocrine peptides influence DNA synthesis in rat and human
small intestinal cells in vitro.
AB - Animal studies suggest a mediator role for neuroendocrine peptides and amines in
regulating cell proliferation in the gastrointestinal epithelium. Our aim was to
examine the effect of serotonin and selected gastrointestinal peptides on DNA
synthesis in a rat and human small intestinal cell line in vitro. IEC-6 and FHs
74 cells were incubated with epidermal growth factor (EGF), insulin-like growth
factor II, glucagon, substance P, neurokinin A, calcitonin gene-related peptide
(GRP, CCGRP), neurotensin and serotonin. The cells were labelled with [methyl-3H]
thymidine and processed for autoradiography. DNA synthesis was evaluated by the
labelling index. Epidermal growth factor, insulin-like growth factor II,
glucagon, and substance P increased the labelling index in a dose-related manner
(P < 0.003). In contrast, a significant dose-dependent reduction of the labelling
index was observed after administration of serotonin and neurokinin A (P <
0.0001). Neurotensin and CGRP did not affect the labelling index. EGF, insulin
like growth factor II, glucagon, substance P, serotonin and neurokinin A may be
important physiological regulators of proliferation, of gastrointestinal cells.
PMID- 9648639
TI - Isoform of Na+, K(+)-ATPase from rumen epithelium identified and quantified by
immunochemical methods.
AB - Using biopsies of rumen epithelium papillae a net influx of [86Rb+] was measured
corresponding to a high concentration of Na+, K(+)-pumps found in [3H]ouabain
binding studies (Kristensen et al. 1995). In the present study the Na+, K(+)
ATPase in papillae homogenates is compared with purified (Na+, K+)-ATPase from
different sources, immunochemically characterized with respect to the isoform of
the hydrolytic alpha subunit and the concentration of pumps substantiated by a
novel immunochemical method. Na+, K(+)-ATPase purified from bovine kidney was
shown to contain one homogeneous high-affinity population of [3H]ouabain-binding
sites (Kd 1.37 nM). The ouabain-binding capacity was 0.82 nmol (mg protein)-1.
Site-directed polyclonal antibodies raised to isoform-specific sequences of the
three known alpha-subunit isoforms and monoclonal alpha 1-specific antibodies
were used for isoform characterization on western blots of peptides separated by
SDS-polyacrylamide gel electrophoresis. All three isoforms were present in Na+,
K(+)-ATPase prepared from bovine brain. The alpha isoform of bovine kidney Na+,
K(+)-ATPase and of rumen epithelium homogenate appeared to be alpha 1 whereas
alpha 2 and alpha 3 were undetectable. Using an alpha 1-specific antibody and
125I-labelled antimouse IgG the content of (Na+, K+)-ATPase in rumen epithelium
was determined by comparison of the signal from known amount of bovine kidney
Na+, K(+)-ATPase on western blots. By this method rumen epithelium was found to
contain 2.6 nmol Na+, K(+)-ATPase (g wet wt)-1, i.e. a similarly high or even
higher concentration than previously seen in ouabain-binding studies on biopsies.
PMID- 9648640
TI - Structure and individuality in psychoanalytic training: the Israeli controversial
discussions.
PMID- 9648641
TI - On loneliness, narcissism, and intimacy.
AB - The complex interplay between narcissistic vulnerability, adolescent development,
and the capacity for intimate relatedness is viewed here from the perspective of
two distinct but interrelated experiential modes of Being and Doing. I offer a
view of loneliness that begins with a critical reappraisal of the concept of
narcissistic relatedness in association with difficulties in establishing
intimacy. These difficulties are due to failures in the developmentally
prescribed intimacy. These difficulties are due to failures in the
developmentally prescribed integration of the experiential modalities of Being
and Doing during the course of late adolescence and young adulthood. The type of
loneliness encountered in adult life, its particular cast and subjectively
experienced nature, are determined by the specific modality around which it has
become primarily organized. Clinical material is presented to illustrate the
meaning of loneliness in the presence of the object, and the paradoxical
inability to be both with the object and without it.
PMID- 9648642
TI - Narcissistic fragility in the process of befriending the unfamiliar.
PMID- 9648643
TI - The emancipation of time from autistic encapsulation: a study in the use of
countertransference.
PMID- 9648644
TI - Two principles of functioning of the affects.
PMID- 9648645
TI - Why Oedipus and not Christ?
PMID- 9648646
TI - The detection of enzyme activity following sodium dodecyl sulfate-polyacrylamide
gel electrophoresis.
AB - More than a hundred different enzymes impinging on aspects of cell function
ranging from carbohydrate and lipid metabolism to signal transduction and gene
expression to biomolecule degradation have been detected by the assay of their
enzymatic activities following SDS-PAGE. The strategies by which this has been
accomplished are as varied as the enzymes themselves and offer testimony to the
creativeness and ingenuity of life scientists. Assay of enzyme activity following
SDS-PAGE is well adapted to identifying the source of catalytic activity in a
heterogeneous protein mixture or a heterooligomeric protein (20), or determining
if multiple catalytic activities reside in a single polypeptide (60). The
alliance of versatile enzyme assay techniques with the molecular resolution of
SDS-PAGE offers a powerful means for meeting the increasing demand for the high
throughput screening arising from protein engineering, combinatorial chemistry,
and functional genomics.
PMID- 9648647
TI - Preparation and characterization of an endogenously fluorescent annexin for
detection of apoptotic cells.
AB - Annexin proteins specifically bind anionic phospholipids such as
phosphatidylserine, which are normally confined to the cytoplasmic leaflet of
cellular membranes. During programmed cell death, or apoptosis, this phospholipid
asymmetry is lost, and anionic phospholipids are exposed on the extracellular
leaflet of the plasma membrane where they are accessible to exogenously added,
labeled annexins. Chemically [e.g., fluoroscein isothiocyanate (FITC)]-modified
annexin V has been widely used to detect and enumerate apoptotic cells by flow
cytometry. We prepared chimeric proteins containing green fluorescent protein
(GFP) fused to annexin V. A chimera containing GFP fused to the C-terminus of
annexin V was soluble and fluorescent, but was unable to bind phospholipids. In
contrast, a chimera containing GFP fused to the N-terminus of annexin V
specifically bound apoptotic cells. GFP-annexin V represents a sensitive and
facile alternative to FITC-annexin V for studies of apoptosis.
PMID- 9648648
TI - Quantitative restriction fragment length polymorphism: a procedure for
quantitation of diphtheria toxin gene CRM197 allele.
AB - Here we present an assay for quantitation of a particular gene allele in DNA
mixtures by means of restriction fragment length polymorphism (RFLP) in
combination with polymerase chain reaction (PCR). We applied the quantitative
RFLP principle for estimation of the relative amount of diphtheria toxin gene
CRM197 allele in Corynebacterium diphtheriae culture DNA samples. The procedure
is based on PCR-mediated generation of an artificial AluI restriction site
specifically with the CRM197 DNA template. After AluI digestion of the PCR
product and polyacrylamide gel electrophoresis of the restriction fragments, the
percentage of CRM197 template in the initial DNA sample was determined by
scanning a gel negative. The method was shown to give a linear response when
applied to template mixtures containing different amounts of CRM197 reference
template. For samples where non-CRM197 DNA was detected by AluI RFLP, we designed
a further allele-specific PCR assay to determine whether the non-CRM197 template
portion was the wild-type toxin gene allele.
PMID- 9648649
TI - Detection of 8-oxoguanine in cellular DNA using 2,6-diamino-8-oxopurine as an
internal standard for high-performance liquid chromatography with electrochemical
detection.
AB - The quantitative aspect of the electrochemical detection method to detect 8-oxo
7,8-dihydroguanine (8-oxoGua) has been improved by using an internal standard. In
addition, emphasis was placed on the reduction of artifactual oxidation of DNA
during isolation and hydrolysis. Nuclear DNA was isolated from rat organs and
purified on an anion-exchange column following treatment with proteinase K and
RNase. DNA hydrolysis to nucleobases or nucleosides was performed using either
formic acid treatment or enzymatic digestion, respectively. The levels of either
8-oxoGua or 8-hydroxy-7,8-dihydro-2'-deoxyguanosine were comparable. For accurate
quantification, 2,6-diamino-8-oxopurine [(NH2)2-OH-Pur], added prior to
hydrolysis, was used as an internal standard for the high-performance liquid
chromatography with electrochemical detection assay. The baseline level of 8
oxoGua in DNA of Sprague-Dawley rats was estimated to be 2 to 5 8-oxoGua residues
per 10(6) DNA bases, with slight differences depending on the tissue origin. In
agreement with the results of previous observations, the level of the oxidized
base in the kidney of animal treated with iron complexed to nitrilotriacetic acid
(Fe-NTA) (15 mg/kg) was three- to fourfold higher than that of untreated rats or
animals treated with a saline solution, while there was no change in 8-oxoGua
levels in the liver and colon of these treated animals.
PMID- 9648650
TI - Affinity purification of yeast cytochrome oxidase with biotinylated subunits 4,
5, or 6.
AB - Null mutants in COX4, COX5a, or COX6, which encode subunits 4, 5, and 6 of yeast
cytochrome oxidase are blocked in assembly of the enzyme. The mutants are
complemented by gene constructs expressing cytochrome oxidase subunits with a
carboxyl terminal extension containing a biotinylation signal sequence. Spectra
and enzyme activities of mitochondria from transformants expressing a
biotinylated subunit indicate restoration of a functional cytochrome oxidase.
Biotinylated cytochrome oxidase can be affinity-purified from mitochondrial
extracts by fractionation on a monomeric avidin column. This method can be used
to purify the enzyme from small amounts of starting material.
PMID- 9648651
TI - Using light scattering to locate less than a microgram of protein per band in
polyacrylamide tube gels after isoelectric focusing.
AB - After separation by isoelectric focusing (IEF) or non-equilibrium pH gradient
electrophoresis (NEPHGE) in 9.2 M urea polyacrylamide tube gels, proteins with Mr
> 20,000 can be precipitated by shaking the gels in 25% methanol. When a fiber
optic illuminator is placed in contact with the end of the gel, the cylindrical
gel transmits light by internal reflection. In regions of the gel where protein
is precipitated, this light is scattered, making it visible when the gel is
viewed in a darkened room against a black background. The sensitivity of the
method is moderate: less than 1 microgram protein per band (in a 3-mm diameter
gel) can be detected. Because the protein in the bands precipitates rapidly (30
min), the solution used (25% methanol) is fairly benign to proteins, and the
apparatus is not expensive, this technique should be useful in several situations
including electrophoretic purification schemes. This method is especially useful
for evaluating the quality of an IEF or NEPHGE tube gel before using it for the
second dimension of a two-dimensional gel.
PMID- 9648652
TI - Study of NADH stability using ultraviolet-visible spectrophotometric analysis and
factorial design.
AB - The chemical stability of nicotinamide adenine dinucleotide coenzyme (NADH/NAD+)
and its derivatives (NADPH/NADP+) was investigated using changes in the UV
visible absorption spectra of these compounds. The spectra of cofactor (reduced
form) were monitored at 340 nm wavelength in different buffers, showing a faster
degradation in phosphate buffer. This was assigned to the adduct formation
between phosphate and NADH (pyridine ring). The three-factor-two-level factorial
design study evaluated the contributions: buffers (phosphate and Pipes 0.1 M),
pH's (6.8 and 7.8), and temperature (25 and 30 degrees C). The freshly prepared
aqueous solutions of coenzyme were analyzed after 40 min under the different
conditions (eight assays in triplicate) of the experiment. The main observed
effects of the NADH oxidation were, in increasing order, pH, temperature, and
buffer without appreciable interactive effects. Therefore, it was verified that
the better conditions for cofactor use were alkaline media employing Pipes buffer
or its derivatives and low temperatures.
PMID- 9648653
TI - An approach to predicting the stabilities of peptide nucleic acid:DNA duplexes.
AB - An approach is described for predicting peptide nucleic acid (PNA):DNA duplex
stability from base sequence by approximating the total free energy of
dissociation, delta G degree tot, for these duplexes as the sum of five
parameters: (a) a nearest-neighbor interaction summation term, sigma Nj delta G
degree j; (b) an initiation term, delta G degree i; (c) a dangling-end
stabilization term, delta G degree e; (d) a PNA:DNA stabilization term per
nearest-neighbor interaction, delta G degree pna; and (e) an ionic strength term,
delta G degree Na. Parameters (a) and (b) are approximated using previously
determined values for DNA:DNA duplexes, whereas parameters (c), (d), and (e) are
empirically determined. These terms are used to calculated delta G degree tot,
which is used in conjunction with a transition enthalpy (delta H degree) value,
also approximated from nearest-neighbor values previously derived for DNA:DNA
duplexes, to calculate a melting temperature (Tm) for the PNA:DNA duplex.
Predicted Tm values calculated by this approach agreed fairly well with measured
values for 11 different PNA:DNA duplexes, as well as with literature values. The
approach also accurately models ionic strength effects.
PMID- 9648654
TI - Aggrecan immobilization onto polystyrene plates through electrostatic
interactions with spermine.
AB - A new procedure for the immobilization of proteoglycans and the core protein
thereof via their carbohydrate chains onto enzyme-linked immunosorbent assay
(ELISA) plate wells is presented. The aggrecan was immobilized via electrostatic
interactions with spermine coupled to glutaraldehyde via Schiff's base, the
latter being directly anchored onto ELISA wells. The amounts of aggrecan bound by
this procedure measured immunochemically were 10-fold greater than those adsorbed
by direct coating. The interaction of aggrecan and spermine may be inhibited by
very small amounts of sulfated glycosaminoglycans or proteoglycans in a
competitive manner, and therefore the system may be used for their quantitation.
Bound aggrecan could react with link protein and therefore the system may be used
for studying interactions of cartilage macromolecules. The method may also be
used for direct quantitation of proteoglycans since the amounts adsorbed, in a
given range of concentrations, are directly proportional to the amounts in
solution.
PMID- 9648655
TI - Determination of gene usage by differential polymerase chain reaction product
hybridization.
AB - All swine VH genes belong to a highly homologous family and have identical leader
sequences, and the swine VH locus contains a single JH. The small number of VH
genes used by the fetus and neonate in the first 6 weeks have unique CDR1 and
CDR2 sequences, permitting each to be identified using specific oligonucleotide
probes. We have used this system as a model for the development of a rapid method
for determining the proportional usage of closely related genes based on
differential polymerase chain reaction (PCR) product hybridization (DPPH). The
validity of the method is demonstrated using mixtures of PCR product containing
known amounts of VH gene DNAs and by comparing data obtained by this method with
those obtained by enumeration of individual hybridizing clones from lymphoid
tissue and peripheral blood B cells. Since DPPH is at least 100-fold more
efficient than the enumeration of individual hybridizing clones, it is especially
useful for analyzing large numbers of samples in population studies. The possible
extension of this method to the usage of other genes is discussed.
PMID- 9648656
TI - Temperature gradient chamber for relative growth rate analysis of yeast.
AB - Relative growth is often used as a phenotypic measure to distinguish mutant and
wild-type yeast or bacterial strains. Differential growth as a function of
temperature is a convenient and accurate means of analyzing differences between
strains. Slight differences in the genotypes of two strains frequently result in
differential growth of the two strains as a function of temperature. We have
developed a chamber for the simultaneous growth of multiple strains in microtiter
plates along a temperature gradient. Image analysis was used to determine colony
area and number at various times as a function of temperature. This chamber
reduces the time required and increases the accuracy in measuring growth as a
function of temperature. This occurs by allowing relative growth to be measured
along a temperature gradient where all other conditions are constant. Two strains
of yeast (Saccharomyces cerevisiae) with a known difference in temperature
dependence of growth were used to demonstrate the performance of this chamber.
PMID- 9648657
TI - Evaluation of taurine metabolism in cats by dual stable isotope analysis.
AB - Taurine kinetics in cats was investigated using a bolus dose of [15N]- and [1,2
13C2]taurine. The comparison of [15N]- and [13C2]taurine kinetics permitted an
evaluation of the extent of taurine transamination. A methodology which involves
N-pentafluorobenzoyl di-n-butylamine derivatization of taurine and GC/MS
measurements of the 15N- and 13C-enrichments in cat urine was developed. Accuracy
of the measurements was determined using pure standard compounds and the results
showed that [13C2]taurine does not interfere with [15N]taurine. In cats, no
differences were observed between both tracers. Therefore, we conclude that
taurine reversible transamination does not occur at a significant level in cats.
PMID- 9648658
TI - High-performance liquid chromatographic determination of insulin in rat and human
plasma.
AB - A rapid and simple isocratic chromatographic procedure for the determination of
insulin in human and rat plasma using reversed-phase (RP) high-performance liquid
chromatography with an ultraviolet/visible detector is described. The method
includes extraction of insulin from human and rat plasma into dichloromethane,
followed by back-extraction into 0.05 N hydrochloric acid. The organic phase was
evaporated under a stream of nitrogen. The aqueous phase was filtered and a 100
microliters aliquot was analyzed on a RP-C18 column eluted with a mobile phase
consisting of a mixture of 74 vol of 0.2 M sodium sulfate anhydrous adjusted to
pH 2.3 with phosphoric acid and 26 vol of acetonitrile. The flow rate was 1.2
ml/min and the wavelength was set at 214 nm. The calibration curve was linear
over the range of 75-800 microIU/ml. The precision of the assay expressed as
coefficients of variation was less than 6% over the entire concentration range.
The recovery for insulin ranged from 79 to 81% from human and rat plasma, with
coefficients of variation less than 6%. The intra- and interassay coefficients of
variation were less than 5.7%. The limit of detection was 50 microIU/ml.
PMID- 9648659
TI - Immobilization of saccharides and peptides on 96-well microtiter plates coated
with methyl vinyl ether-maleic anhydride copolymer.
AB - We have previously reported a method to immobilize protein ligands on microtiter
plates coated with methyl vinyl ether-maleic anhydride copolymer (MMAC) [Isosaki,
K., et al. (1992) J. Chromatogr. 597, 123-128]. In this study, we improved the
MMAC method to efficiently immobilize not only small ligands such as peptides and
oligosaccharides, which could not be efficiently immobilized previously, but also
heparin via its reducing end. Amino and hydrazino groups were introduced to MMAC
coated microtiter plate wells by coupling to acid anhydride groups of MMAC with
1,6-hexamethylenediamine and adipic acid dihydrazide, respectively. The amino
groups introduced were allowed to react with peptides by use of divalent cross
linkers. Hydrazino groups were allowed to react with formyl groups of saccharides
by reductive amination. Peptides and oligosaccharides were immobilized in a dose
dependent manner by these methods. In the case of the angiotensin peptide thus
immobilized, the detection limit by monoclonal antibodies was as low as 0.1-1
fmol peptide per well. Application of 20-200 nmol oligosaccharides to the well
was sufficient to immobilize and subsequently detect lectins. Furthermore,
heparin immobilized on the hydrazinocoated wells was successfully used for the
binding assay of annexin IV.
PMID- 9648660
TI - Detection and quantitation of 59Fe-labeled proteins using storage
phosphorimaging.
PMID- 9648661
TI - Cost- and time-efficient gel electrophoresis for mini-gel systems.
PMID- 9648662
TI - Immuno- and gold staining of a single western blot.
PMID- 9648663
TI - Enzymatic detection of ultraviolet-induced pyrimidine (6-4) pyrimidone
photoproducts at nucleotide resolution in Saccharomyces cerevisiae.
PMID- 9648664
TI - A new method for evaluation and dietary therapy of congenital: deficiencies of
amino acid metabolic enzymes. Linear system analysis and optimization of feedback
inputs for the metabolic pathways of lysine, methionine and isoleucine.
AB - We intended to elucidate an integrated mathematical model of amino acid
metabolism and we propose a system for optimization treatment of disturbed
metabolic states caused by congenital enzyme deficiencies. Our analysis focused
on the metabolic pathway starting at asparaginic acid proceeding to isoleucine,
methionine and lysine. The rate of change in the concentration of the biochemical
species was expressed as 21 linear rate equations. We obtained the rate constants
and the magnitude of feedback from reported experimental data. Linear systems
analysis revealed that the metabolic system under study was stable but
uncontrollable. These properties were insensitive to changes in the magnitude of
feedback. To show the effect of optimizing the feedback so that it minimizes the
square of the concentration of the species and the control input, we analyzed the
impulse response of the species, transient response and the singular value of the
system for four cases; (1) at the physiological state without optimizing the
feedback, (2) at the physiological state attained after optimizing the feedback,
(3) at the pathophysiological state attained with enzyme deficiency states for
lysine and methionine metabolism without optimizing the feedback, and (4) at the
pathophysiological state attained after optimizing the feedback for enzyme
deficiencies. In the enzyme deficient model, the impulse response oscillated and
lasted longer than that in the physiological state. These changes appeared even
in the species on other branched pathways. The singular value was elevated in the
enzyme deficient state. By optimizing the feedback, all the impulse responses in
the enzyme deficient state recovered to nearly those in the normal physiological
state. Similarly, the transient response and the singular value in the enzyme
deficient state recovered to nearly the normal physiological values. We
elucidated the numerical value of the feedback gain for this optimization. The
present analysis is useful for the evaluation of the integrated properties of
amino acid metabolism and the optimization technique is potentially of use for
determining a treatment course for congenital metabolic enzyme deficiencies.
PMID- 9648665
TI - The synchronization of recruitment-based activities in ants.
AB - A simple model of recruitment-based foraging in ants illustrates the idea that
synchronized patterns of activity can endow a colony with the ability to forage
more efficiently when a minimal number of active individuals is required to
establish and maintain food source exploitation. This model, which can be
extended to other activities that involve recruitment, may help explain why
bursts of synchronization have been observed in several species of ants.
PMID- 9648666
TI - Effect of environmental complexity on salt-adaptation in Sorghum bicolor.
AB - Individual plants of Sorghum bicolor mature different adaptive reactions to
salinity. The positive correlation between the frequency of specific reactions
and the tolerance level of plants with that specific reaction results from
adaptive determinism (AD). The effect of complexity in environmental conditions
on AD in plants adapting for the first time to salinity, A0, and in their
offspring A1 was compared. Environmental complexity increases when uncontrolled
factors besides salinity affect plants. The diversity of reactions of plants
correlates positively with environmental complexity. AD correlates negatively to
environmental complexity in A1. In contrast, environmental complexity has no
effect on AD in A0. A1 are more tolerant to salinity than A0: A1 inherited
adaptive information. The likelihood that A1 plants are exposed to the same
uncontrolled factor as their parent is low, and so the decrease of AD in A1 due
to environmental complexity suggests that: (1) the information inherited is
specific to saline conditions; (2) AD results mainly from inherited pre-existing
information; plants react as informatively closed systems: saline conditions
trigger the expression of an adaptive, pre-existing program. For A0, conclusions
are: (1) the adaptive reaction is not an expression of pre-existing information;
(2) AD emerges during the adaptation process: the environment imprints adaptively
the plant's development. In this case, plants react as open systems in terms of
information.
PMID- 9648667
TI - Effects of feedback inhibition on transit time in a linear pathway of Michaelis
Menten-type reactions.
AB - An analysis of the effects of external and internal metabolites on the steady
state behavior of linear pathways comprising a sequence of three Michaelis-Menten
type reactions with and without a simple feedback inhibition (i.e. an interaction
of an internal metabolite with the pathway) is performed with respect to the
transit time tau by its formulation as rectangular-hyperbolic functions of the
flux J, instead of direct expressions in terms of the external metabolite
concentrations. For a given concentration of the external metabolite M1
(substrate of the pathway) or M4 (product of the pathway), the flux J has a lower
value in the pathway with feedback inhibition than in the pathway without
feedback inhibition. With variation in the M1 concentration the transit time tau
shows a concave relationship with the flux J which is virtually identical for
both pathways, yielding a minimum at a certain value of J. With variation in the
M4 concentration the transit time tau monotonously decreases with higher value of
J, and for a given value of J the feedback inhibition allows a lower transit
time. This effect is enhanced with stronger feedback inhibition, and is in turn
greatly reduced with higher values of total concentration and rate constants for
the first enzyme in the pathway.
PMID- 9648668
TI - Second conference on foundations of information science: the quest for a unified
theory of information.
PMID- 9648669
TI - The informational perspective: an overview of the issue.
AB - Papers arising out of the 1996 Conference on the Foundations of Information
Science are introduced. A key motif is the continual violation and restoration of
consistency, percolating and precipitating along vertical chains of informational
objects.
PMID- 9648670
TI - The cosmic environment for the growth of complexity.
AB - The unifying scenario fo cosmic evolution is outlined by following the natural
changes among radiation, matter and life in standard, big-bang cosmology. Using
aspects of non equilibrium thermodynamics, especially energy flow considerations,
we argue that it is the contrasting temporal behavior of various energy densities
that have given rise to the environments needed for the emergence of galaxies,
stars, planets, and life forms. We furthermore argue that a necessary (though
perhaps not sufficient) condition--a veritable prime mover--for the emergence of
such ordered structures of growing complexity is the expansion of the Universe
itself. Neither demonstrably new science nor appeals to non-science are needed to
explain the impressive hierarchy of generative change, from atoms to galaxies,
from cells to society.
PMID- 9648671
TI - Information loss in the continuum limit and Schrodinger's equation in an
electromagnetic field.
AB - Since the time of Einstein's work on Brownian motion it has been known that
random walks provide a microscopic model for the diffusion equation. Less well
known is the fact that some instances of Schrodinger's equation occur naturally
in the description of the statistics of these same walks and thus have classical
contexts which are distinct from their usual association with quantum mechanics.
An interesting feature of these models is the fact that the information which
relates Schrodinger's equation to its classical context is not contained in the
partial differential equation itself, but is lost in the continuum limit which
gives rise to the equation. In this article we illustrate the above by showing
that Schrodinger's equation for a particle in an electromagnetic field in 1 + 1
dimension occurs as a continuum limit of a description of a classical system of
point particles on a lattice. The derivation shows that the information lost in
the continuum limit is necessary to link the mathematics to the physical context
of the equation.
PMID- 9648672
TI - Quantum gravity and life.
PMID- 9648673
TI - Dimensional symmetry breaking, information and fractal gravity in Cantorian
space.
AB - We derive the exact expectation value and standard deviation for the
dimensionality of Cantorian spacetime. Connections to time symmetry breaking,
information and the generalization of complex numbers are considered. Finally a
link between general relativity and Cantorian spacetime is proposed which amounts
to the claim that fractalization is the origin of gravity.
PMID- 9648674
TI - Entropy and predictability of information carriers.
AB - The structure of linear strings carrying information is investigated by means of
entropy concepts. First conditional entropy and transinformation are introduced
and several generalizations are discussed. The capability to describe the
structure of information carriers as DNA, proteins, texts and musical strings is
investigated. The relation between order and the predictability of informational
strings is discussed. As examples we study the mutual information function of
virus DNA and several long proteins. Further we show some (rather formal)
analogies to the structure of texts, and strings generated by musical melodies.
It is shown that several information carriers show long-range correlations.
PMID- 9648675
TI - Dynamics of time and information in dynamic time.
AB - Time is intrinsically locally asynchronous, dynamic in itself, and self
organizing in having locally asynchronous time precipitate further asynchronous
time while leaving behind globally synchronous time. The resulting global
synchronism is skewed in locally asynchronous time, while being vertical to the
effected globally synchronous time. Information is a dynamic attribute of time
and can be represented as a skewed synchronism in locally asynchronous time.
Information originates in the communication among asynchronous times of a local
character.
PMID- 9648676
TI - Information gain by endo-observers: chances and limitations.
AB - Endo-observers can be described and classified on the basis of a novel two
dimensional scheme. One axis stands for the observer's style of knowledge
acquisition, whereas the other axis corresponds to the observer's style of
knowledge representation. In this way several problems concerning the relation
between the endo-observer and the exo-system can be studied more systematically.
Among other things, it is shown that there are two complementarity relations
which restrict the observer's capacity of information gain: a duality between
structure and dynamics (an increased information gain on the structure of the
endo-system implies a reduced information gain on its dynamics, and vice versa),
and a duality between the predictive and the explanatory power of a model.
Connections with the problem of hermeneutics are outlined.
PMID- 9648677
TI - Exaptation and torsion: toward a theory of natural information processing.
AB - Several conundrums are provoked by attempts to provide algorithmic descriptions
of natural phenomena. A characteristic feature of natural computation is a
breakdown in the formal simulation relation. This is called hermeneutic torsion,
and is formally the failure to commute of a diagram describing homomorphisms
between dynamical systems. This torsion is a source of computational power. For
example, it is deeply involved with phenomena such as exaptation, wherein an
existing structure is recruited for a novel function. Exaptation occurs
continually at the macromolecular level and is fundamentally nonalgorithmic; our
system-theoretic models of computation deal with structural descriptions for
which a functional semantics must be assigned in advance, and a natural system
continually 'diagonalizes out' of this semantics. This perspective clarifies the
nature of computing power and encourages consideration of a new kind of
transcomputational complexity.
PMID- 9648678
TI - An information typology for understanding living systems.
AB - It is argued that we can improve our understanding of living systems by focusing
on their informational processes. Recent developments, primarily in evolutionary
biology, cybernetics and systems theory, suggest that informational processes are
of at least two, and probably three, different types; and that the interaction of
these types can be seen as a basis for the self-construction of living systems.
Following the work of Csanyi and Kampis, a distinction is drawn between
referential and nonreferential information. This typology is further extended to
include statereferential information. The statereferential type serves to lend
stability to informational arrangements (organization) that are viable so that
they may be propagated in space and time.
PMID- 9648679
TI - Time, reflectivity and information processing in living systems: a sketch for the
unified information paradigm in biology.
AB - The recognition activity of biomacromolecules based on quantum non-demolition
measurements is regarded as the basis of information processing. Reflective
arrows in the set of mappings appearing from quantum measurements correspond to
the Godel numbers created inside a system overcoming its incompleteness. Temporal
evolution is a consequence of contradictory statements about the whole system in
which a reflective arrow is both an element of the system and its signification.
It results from the solution of a paradox in which the system generates new
descriptions non-deducible from its previous states. The active combinatorial
process of self modification of information, being an internalized language game,
allows a system to create Godel numbers. The whole system is constructed
according to percolating coherent events, providing 'vertical' self-assembly that
is predetermined by the encoding and internal language games.
PMID- 9648680
TI - Biological information and laws of nature.
PMID- 9648681
TI - Dynamic information processing in natural and artificial olfactory systems.
AB - A new strategy for building artificial gas sensing systems is suggested based on
knowledge of the dynamic response mechanism of the olfactory system. Difficulties
with the processing of time-dependent inputs by neural networks are discussed.
PMID- 9648682
TI - The Feigenbaum scenario as a model of the limits of conscious information
processing.
AB - The Feigenbaum scenario of the mathematical period doubling sequence from order
to deterministic chaos has led to new insights about the nonlinear dynamics of a
wide variety of physical and biological systems. Multiple realms from purely
mechanical systems, fluid dynamics and weather to the patterns of biological
growth and the dynamic of the heart, hormone and brain rhythms have been found to
exhibit aspects of the Feigenbaum period doubling sequence. We explore the
possibility that the Feigenbaum scenario can be extended to experiences of
sensation, perception and human cognition as well. We also review the empirical
data that supports the view that the Feigenbaum scenario of the period doubling
sequence may portray an important limit in conscious information processing. We
conclude that a major function of consciousness may be to transform the
nonlinear, irrational and difficult to predict dynamics of unconscious nature
into the more linear, rational and predictable psychodynamics that make human
experience and social life possible.
PMID- 9648683
TI - Consciousness as a self-organizing process: an ecological perspective.
AB - The evolution of consciousness is seen in the context of energy-driven evolution
in general, where energy and information are understood as two sides of the same
coin. From this perspective consciousness is viewed as an ecological system in
which streams of cognitive, perceptual, and emotional information form a rich
complex of interactions, analogous to the interactive metabolism of a living
cell. The result is an organic, self-generating, or 'autopoietic', system,
continuously in the act of creating itself. Evidence suggests that this process
is chaotic, or at least chaotic-like, and capable of assuming a number of
distinct states best understood as chaotic attractors.
PMID- 9648684
TI - Conscious experience and information.
AB - Conscious experience, our main source of information, has special properties.
Primary among them is privacy, or privileged access by persons to their own
conscious states. The consequent theoretical and practical problems for research
on both consciousness and information are delineated.
PMID- 9648685
TI - Social information: the person is the message.
AB - Assumptions that Shannon's concepts cannot extend to social systems are
challenged by showing that social information measures the reduced uncertainties
individuals have about the systemic effects of each other's behavior. The
'meaning' of individual actions is their collective consequences, which also
measure reductions in systemic uncertainties about collective environments.
Meaning is communicated through messages using media such as values, ethics and
morals, which encourage individuals to act predictably and replicate the
improbable behaviors characterizing particular societies. When individuals
internalize meaning, their personal identities communicate societal priorities to
future generations.
PMID- 9648686
TI - Information and the unfolding of social life: molecular-biological resonances
reaching up to the economy.
AB - The much vexed analogy between cells, organisms, and societies receives a new
treatment here. It is argued that, based on an enlarged view on the relationship
between information and life, one can approach economy from an unusual angle: the
accounting processes that take place in every productive unit and commercial
organization. Such accounting processes have been historically developed in order
to coordinate the economic 'physiology' of complex societies. In this sense, the
convergence which can be found amongst the abstract, coordinating operations
performed by cellular signaling systems, vertebrate nervous systems, and
entrepreneurial accounting systems appears as a relevant theoretical item to
analyze (the abstract organization of what can be called information 'phase
transitions'). Its development lends support to the cogency of a 'vertical'
information science approach.
PMID- 9648687
TI - Dynamics and information processing in adaptive systems.
AB - An adaptive system is capable of functioning despite some degree of environmental
uncertainty. This requires an ability to identify relevant states of the
environment, to adjust the value of internal variables so as to maintain a
characteristic pattern of activity and, of course, to respond appropriately to
environmental stimuli. Biological systems have responded to this challenge by
developing information processing systems that are highly compatible with their
functions. In this paper we analyze the relationship between dynamics and
information processing in biological systems and refer to basic principles of
biological information processing. An important trend that can be observed is
that the specialization of information processing functions increases with the
complexity of the environment faced by the systems. At the level of human
populations, man-made organizations in particular, our study suggests that the
design of computer-based information systems must be sensitive to the existing
biological infrastructure if they are to effectively extend the cognitive and
computational capabilities of organizations.
PMID- 9648688
TI - Soft mathematics and information dynamics.
AB - We present a brief overview of a new framework for interdisciplinary
collaboration toward understanding the fundamentals of information dynamics in
social systems. The need for a new mathematics is noted, and a promising
component, soft mathematics, is described.
PMID- 9648689
TI - Information and third order ontology.
AB - The question of 'a unified theory of information' is addressed from the logical
position of many-valued ontologies. Information is described as an operational
factor which forms a trans-contextural bridge between disjunct ontological
systems (or monocontextures).
PMID- 9648690
TI - Ontological measurement.
AB - Endophysics ultimately deduces an indefinite interface between an object and an
observer. Objects, given such an interface, cannot be distinguished from the
measurement process used to identify them. Evolutionary processes comprising of
emergent properties and adaptability are seen in a new light. The concept of
indefiniteness and/or paradox appears on the surface to be based on the
epistemological framework of the Cartesian cut. However, perpetual processes
consisting of generation and resolution of paradoxes are beyond the
epistemological framework of measurement. They lead to the notion of progression,
which one can refer to as ontological (or inherent) measurement.
PMID- 9648691
TI - Cybersemiotics: a transdisciplinary framework for information studies.
AB - This paper summarizes recent attempts by this author to create a
transdisciplinary, non-Cartesian and non-reductionistic framework for information
studies in natural, social, and technological systems. To confront, in a
scientific way, the problems of modern information technology where
phenomenological man is dealing with socially constructed texts in
algorithmically based digital bit-machines we need a theoretical framework
spanning from physics over biology and technological design to phenomenological
and social production of signification and meaning. I am working with such
pragmatic theories as second order cybernetics (coupled with autopolesis theory),
Lakoffs biologically oriented cognitive semantics, Peirce's triadic semiotics,
and Wittgenstein's pragmatic language game theory. A coherent synthesis of these
theories is what the cybersemiotic framework attempts to accomplish.
PMID- 9648692
TI - The emerging global community.
AB - Human society may be viewed as an evolving system. From time to time, there
occurs the equivalent of a phase shift, or more appropriately, a 'cultural
discontinuity'. In each case, such a discontinuity is preceded by, and caused by
the emergence of a constellation of new technologies. During and following such a
discontinuity previously existing cultural institutions become modified, or
abolished all together, while new ones arise. The paper considers the impact of
the Industrial and the Electronic revolutions on absolute monarchy, slavery, the
State, war, and the emergence of an integrated global community.
PMID- 9648693
TI - The making of the information society: driving forces, 'Leitbilder' and the
imperative for survival.
AB - In the field of science-technology-society, there are three one-sided approaches
to analyzing the spread of the Internet: technology-push, economy-pull, and
community-pull. Information science, when dealing with the transformation of our
societies, will have to cover all of them and even try to find out missing links.
We propose adding the analysis of metaphors accompanying the introduction and
diffusion of new technologies, and evaluating metaphors and technologies using
the criterion of how well they are shaped to meet global challenges. We conclude
that contrary to ideological promises the capability of society to generate
survival-relevant information will not be improved by establishing the so-called
data highway per se, unless additional requirements are met which refer to higher
information levels of knowledge and wisdom.
PMID- 9648694
TI - Webometry: measuring the synergy of the World-Wide Web.
AB - This is the second progress report on the webometry project: acquisition of data
regarding the density of links on the world-wide web (WWW). We illustrate the
primary visualization strategy, the synergy matrix, in the case of a model subnet
of nine nodes.
PMID- 9648695
TI - The relativist stance.
AB - The two mindsets of absolutism and relativism are juxtaposed, and the relational
or relativist stance is vindicated. The only 'absolute' entity which undeniably
exists, consciousness has the reality of a dream. The escape hatch from this
prison is relational, as Descartes and Levinas found out: Unfalsified relational
consistency implies exteriority. Exteriority implies infinite power which in turn
makes compassion inevitable. Aside from ethics as a royal way to enlightenment, a
new technology called 'deep technology' may be accessible. It changes the whole
world in a demonstrable fashion by manipulation of the micro frame--that is, the
observer-world interface.
PMID- 9648696
TI - Occupational asthma caused by tetrachlorophthalic anhydride: a 12-year follow-up.
PMID- 9648697
TI - Indoor allergens and longitudinal FEV1 decline in older adults: the Normative
Aging Study.
AB - We investigated the relationship between home allergen exposure and decline in
FEV1 in 10 asthmatic and 30 randomly selected, age-matched, nonasthmatic
participants in the Normative Aging Study. We defined asthma as subject-reported
wheezing apart from colds, with either a physician's diagnosis of asthma or a
methacholine PD20 FEV1 of 8.6 micromol or less. We examined the relationship
between the annual decline in FEV1 and the concentrations of the cockroach
(Blattella germanica) allergens Bla g 1 and Bla g 2, the dust mite
(Dermatophagoides pteronyssinus and Dermatophagoides farinae) allergens Der p 1
and Der f 1, and the cat (Felis domesticus) allergen Fel d 1 in house dust
specimens. Bla g 1 (-79.8 ml/yr, p = 0.0006) and Bla g 2 (-40.81 ml/yr, p =
0.0004) were significant predictors of decline in FEV1 after adjustment for age,
smoking, and baseline FEV1. These results were unchanged after elimination of the
asthmatic subjects from the analysis. We conclude that cockroach allergen levels
in homes is a risk factor for accelerated decline in FEV1 independent of airway
responsiveness.
PMID- 9648698
TI - The common cold: effects of intranasal fluticasone propionate treatment.
AB - OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to
study the effect of the intranasal corticosteroid, fluticasone propionate (FP),
in the naturally occurring common cold. METHODS: One hundred ninety-nine young
adults received high-dose FP (200 microg four times daily) or placebo beginning
24 to 48 hours after onset of the common cold for 6 days. All symptoms were
recorded on diary cards on days 1 to 20, and clinical examinations were carried
out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7
for detection of rhinoviruses (found in 105 subjects) and Streptococcus
pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52
subjects) in the nasopharynx. RESULTS: In general, FP treatment had no clinically
recognizable effects on the symptoms of the common cold, although it
significantly reduced nasal congestion and cough on some study days. After
treatment, rhinoviruses were cultured more often in the FP treatment group (37%
vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP
treatment produced no changes in the colonization of pathogenic bacteria in the
nasopharynx. Some symptoms of common cold were significantly more severe during
days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S.
pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n =
33). CONCLUSION: FP treatment does not have any marked effects on the symptoms of
the common cold. FP treatment induced prolonged shedding of viable rhinoviruses.
Some symptoms of the common cold were significantly more severe in subjects with
pathogenic bacteria in the nasopharynx.
PMID- 9648699
TI - Subjects with seasonal allergic rhinitis and nonrhinitic subjects react
differentially to nasal provocation with chlorine gas.
AB - BACKGROUND: Nasal irritation and associated symptoms (nasal congestion,
rhinorrhea, and sinus headache) are important elements of the response to indoor
and outdoor air pollution. Marked interindividual variability in such symptoms
has been suggested clinically and epidemiologically, but little experimental data
exist on this issue. OBJECTIVE: We sought to test the hypothesis that subjects
with seasonal allergic rhinitis (SAR) exhibit a more marked physiologic response
(congestion) after nasal irritant provocation than do nonrhinitic subjects.
METHODS: We studied eight subjects with SAR and eight nonrhinitic subjects;
subjects with SAR were studied out of season. In a single-blind crossover study,
subjects had their nasal airway resistance (NAR) measured in triplicate before,
immediately after, and 15 minutes after a 15-minute exposure to either filtered
air or 0.5 ppm chlorine in filtered air, administered through a nasal mask in a
climate-controlled chamber. Log-transformed NAR values were analyzed in a
repeated-measures analysis of variance model, with confirmatory testing using
paired t tests. RESULTS: The net (chlorine minus air day) percent change in NAR
from baseline (before exposure) to immediately after exposure was +24% in the SAR
group and +3% in the nonrhinitic group (p < 0.05). The corresponding net changes
from baseline to 15 minutes after exposure were +21% in the SAR group and -1% in
the nonrhinitic group (p < 0.05). CONCLUSIONS: The observed augmented nasal
congestive response of subjects with SAR versus nonrhinitic subjects to a
controlled low-level chemical irritant provocation is consistent with
epidemiologic surveys showing a higher prevalence of nasal symptoms among
subjects with SAR than nonrhinitic subjects in environments involving irritant
air pollutants.
PMID- 9648700
TI - Latex allergy and latex sensitization in children and adolescents with
meningomyelocele.
AB - BACKGROUND: The high prevalence of clinical latex allergy and latex sensitization
in children with meningomyelocele has been widely reported. It has also been
noted that these same children have a higher than expected prevalence of atopic
disease. It would be useful to have a safe, sensitive, and specific skin test to
detect latex sensitivity and to know how well this test compares with available
in vitro tests. It would likewise be helpful to know as fully as possible the
characteristics of the individual and to evaluate the relative importance of
factors suspected to contribute to clinical latex allergy and latex sensitization
in this population. METHODS: A group of 116 children and adolescents 1 to 20
years of age were recruited for the study. An extensive history of latex allergy,
atopic diseases, and surgical procedures was taken on all subjects. Each subject
had either a latex skin test or an in vitro study for latex-specific IgE, and 67
subjects had both tests simultaneously. Eighty-five subjects had epicutaneous
skin tests to a panel of environmental allergens. RESULTS: Overall, 25 of 116
(21.5%) subjects had a history of clinical latex allergy, and 51 of 116 (44%)
were sensitized to latex. The sensitivity and specificity of skin tests for
clinical latex allergy were slightly greater than for the in vitro test (100% vs
95.8% and 82.3% vs 68.9%, respectively). The positive predictive value and
negative predictive value of skin testing for clinical latex allergy were also
greater (67.6% vs 50% and 100% vs 98.1%, respectively). Age was found to be a
significant variable for both latex allergy and latex sensitization. The number
of surgical procedures undergone and the presence of positive skin test responses
to environmental allergens were significantly correlated with latex sensitization
but not with clinical allergy to latex. CONCLUSIONS: A sensitive, specific, and
safe skin test for latex sensitivity appears superior to in vitro testing for
latex allergy. Age, number of surgical procedures, and the presence of positive
allergen skin test responses are significantly correlated with latex
sensitization. Age alone is significantly correlated with clinical allergy to
latex.
PMID- 9648701
TI - Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase
A2 induces specific T-cell anergy in patients allergic to bee venom.
AB - BACKGROUND: Specific immunotherapy with honeybee venom (BV) is highly effective,
but allergic side effects can occur during treatment. Immunotherapy with peptides
containing major T-cell epitopes of the relevant allergen or allergens provides
an alternative strategy without these problems. OBJECTIVE: The study investigates
the immunologic mechanisms and clinical effects of immunotherapy with T-cell
epitope peptides of the major BV allergen, the phospholipase A2 (PLA). METHODS:
Five patients with IgE-mediated systemic allergic reactions to bee stings were
treated with a mixture of three T-cell epitope peptides of PLA. Ten patients
allergic to BV receiving whole BV immunotherapy served as control subjects.
Increasing doses of the peptide mixture, up to a maintenance dose of 100 microg,
were administered subcutaneously within 2 months. The patients were then
challenged with PLA and 1 week later with a bee sting. The cellular and humoral
immune response was measured in vitro. RESULTS: No allergic side effects were
caused by the peptide immunotherapy, and all patients tolerated the challenge
with PLA without systemic allergic symptoms. Two patients developed mild systemic
allergic reactions after the bee sting challenge. After peptide immunotherapy,
specific proliferative responses to PLA and the peptides in peripheral blood
mononuclear cells were decreased in successfully treated patients. The production
of TH2 and TH1 cytokines was inhibited, and B cells were not affected in their
capacity to produce specific IgE and IgG4 antibodies. Their levels increased
after allergen challenge in favor of IgG4. CONCLUSIONS: Immunotherapy of BV
allergy with short T-cell peptides of PLA induces epitope-specific anergy in
peripheral T cells and changes the specific isotype ratio in a fashion similar to
that of conventional immunotherapy in successfully treated patients.
PMID- 9648702
TI - Juniperus oxycedrus: a new allergenic pollen from the Cupressaceae family.
AB - BACKGROUND: Cupressaceae allergy is a worldwide pollinosis caused by several
species. Some species in limited geographic areas pollinate in fall and winter.
Juniperus oxycedrus matches these features. OBJECTIVE: We sought to define the
immunochemical, allergologic, and environmental aspects of J. oxycedrus pollen.
METHODS: Pollen extract from J. oxycedrus was prepared and characterized by
biochemical analysis and human specific IgE binding by means of ELISA and
immunoblotting. A 3-year phenological study was conducted to define the
pollinating period of J. oxycedrus. Forty consecutive patients allergic to
cypress were recruited in two areas and divided into two groups according to
their exposure to J. oxycedrus pollen. Clinical evaluation, skin prick tests, and
specific IgE determination with J. oxycedrus, J. ashei, and Cupressus arizonica
extracts were carried out on both groups. RESULTS: J. oxycedrus pollen extract
was obtained, and it showed specific IgE binding and wide cross-reactivity with
other Cupressaceae species. The extract caused a positive skin test response in
all the patients tested, with about 80% of them having detectable specific IgE.
Symptoms related to J. oxycedrus pollen exposure were recorded in 72% of the
directly exposed patients and occasionally in 9% of the nonexposed patients. In
the Mediterranean coastal area considered, J. oxycedrus was the first
Cupressaceae species that started to pollinate at the beginning of November and
ended in the first part of December. CONCLUSIONS: J. oxycedrus represents a newly
characterized pollen species of the Cupressaceae family that cross-reacts with
other members of the same family. Subjects with cypress allergy have in vivo and
in vitro positive test responses for J. oxycedrus and can show symptoms when
exposed to its pollen. Finally, the most important feature of J. oxycedrus is its
early pollinating period in southern Europe (Italy), causing a further extension
of the cypress pollen season in areas where other Cupressaceae species are
present.
PMID- 9648703
TI - The effects of monosodium glutamate in adults with asthma who perceive themselves
to be monosodium glutamate-intolerant.
AB - BACKGROUND: Many previous clinical studies of food-induced asthma suffer from
inadequate baseline or control data. A statistically valid, randomized, double
blind, placebo-controlled, monosodium glutamate (MSG)-challenge protocol was
developed for identifying early and late asthmatic reactions in an individual.
OBJECTIVE: We sought to determine whether MSG would induce bronchoconstriction in
a group of adults with asthma who perceived that they were MSG sensitive.
METHODS: Twelve subjects (seven women, mean age 35.3 years) with clinically
documented asthma and a perception of MSG-induced asthma were recruited. FEV1 and
peak expiratory flow data were obtained for 3 whole control days, as well as time
matched data for 3 separate challenge days (1 gm MSG, 5 gm MSG, and 5 gm lactose
[placebo]). Opaque capsule challenges were given as a single dose in the morning
after an overnight fast. Subjects complied with an elimination diet throughout
the study. Nonspecific bronchial hyperresponsiveness was measured at baseline,
after the control days, and at the conclusion of the challenges. Venous blood
samples were taken at baseline and on each challenge day to determine soluble
inflammatory marker (eosinophil cationic protein and tryptase) activity. RESULTS:
No immediate or definite late asthmatic reactions occurred. One subject's FEV1
declined more than 15% on MSG challenge, but 95% confidence limits for the
control-day spirometry showed that this decline was within her daily variation,
hence the challenge was deemed to be negative. No significant changes in
bronchial hyperresponsiveness or soluble inflammatory markers were found.
CONCLUSIONS: MSG-induced asthma was not demonstrated in this study. This study
highlighted the importance of adequate baseline and control data and indicated
that such a rigorous protocol for individual assessment is feasible.
PMID- 9648704
TI - Molecular characterization of a cross-reactive Juniperus oxycedrus pollen
allergen, Jun o 2: a novel calcium-binding allergen.
AB - BACKGROUND: Species belonging to the Cupressaceae family are a relevant source of
allergens that are present in a wide number of countries. OBJECTIVE: We sought to
identify, purify, and characterize recombinant allergens from Juniperus
oxycedrus, a species belonging to the Cupressaceae family. METHODS: Double
stranded cDNA was synthesized from mRNA and cloned into the lambda-ZAP expression
vector. IgE screening of the library was performed with a pool of sera from
subjects allergic to Cupressaceae. A recombinant 6xHis-tagged Juniperus oxycedrus
allergen, Jun o 2, was expressed in Escherichia coli and purified by Ni2+
affinity chromatography. It was studied further by immunoblotting inhibition with
pollen extracts from other Cupressaceae, Oleaceae, Urticaceae, and Graminaceae.
The role of protein-bound calcium on the allergen's IgE-binding capacity was
tested in a plaque assay in the presence or absence of EGTA. RESULTS: A cDNA
coding for a newly identified Juniperus oxycedrus pollen allergen, rJun o 2, was
isolated. The deduced amino acid sequence contained four typical Ca2+ binding
sites and showed a significant sequence similarity to calmodulins. Depletion of
Ca2+ in the plaque assay led to a loss of IgE-binding capacity of rJun o 2.
Immunoblotting inhibition revealed that J. oxycedrus, J. ashei, Cupressus
arizonica, C. sempervirens, Parietaria judaica, Olea europaea, and Lolium perenne
pollen extracts were able to inhibit IgE binding to blotted rJun o 2 at different
concentrations. CONCLUSION: rJun o 2 contains IgE-binding epitopes shared by
taxonomically unrelated species, and therefore it can be regarded as a new
panallergen. These findings could contribute to an explanation for the phenomenon
of multiple positive test results in polysensitized patients and the potential
symptom-eliciting role of allergenic sources previously not encountered.
PMID- 9648705
TI - Diesel exhaust particles stimulate human airway epithelial cells to produce
cytokines relevant to airway inflammation in vitro.
AB - BACKGROUND: Epidemiologic and experimental studies suggest that air pollution
such as diesel exhaust particles (DEPs), one of the important air pollutants, may
play a role in the increasing prevalence of allergic airway diseases. OBJECTIVE:
We studied the effect of suspended particulate matter (SPM) and its main
component, DEPs, on the production of IL-8 and granulocyte-macrophage colony
stimulating factor (GM-CSF) by human airway epithelial cells in vitro. METHODS:
SPM obtained from high-volume air samplers and DEPs were added to cultured human
nasal polyp-derived upper airway, normal bronchial, and transformed bronchial
epithelial cells. Production of GM-CSF and IL-8 by airway epithelial cells was
evaluated. RESULTS: Nontoxic doses of DEPs showed a significant stimulatory
effect on IL-8 and GM-CSF production by these three kinds of epithelial cells in
a dose- and time-dependent fashion. SPM had a stimulatory effect on GM-CSF, but
not IL-8, production. These effects were abrogated by treatment with a protein
synthesis inhibitor, cycloheximide, suggesting that the process required a de
novo protein synthesis. On the double-chamber plates, airway epithelial cells
responded to DEPs only when they were stimulated from the apical sides, which can
be a model for in vivo environments. Neither charcoal nor graphite showed such
stimulatory effects, indicating that the activity of DEPs did not derive from
their particulate nature. Benzo(a)pyrene, one of the main aromatic hydrocarbons
contained in DEPs, showed a stimulatory effect on the release of the cytokines,
and this organic substance might have a causative effect on of the potency of
DEPs. CONCLUSION: We conclude that SPM and DEPs, its main component, might be
important air pollutants in the activation of airway epithelial cells for the
release of cytokines relevant to allergic airway inflammation.
PMID- 9648706
TI - Identification of IL-16 as the lymphocyte chemotactic activity in the
bronchoalveolar lavage fluid of histamine-challenged asthmatic patients.
AB - OBJECTIVE: We have previously demonstrated that the earliest lymphocyte
chemotactic factors present in bronchoalveolar lavage fluid (BALF) of subjects
with atopic asthma after subsegmental antigen challenge are IL-16 and MIP-1alpha,
of which IL-16 appears to contribute a majority of the chemotactic activity.
Because IL-16 is released in vitro after histamine stimulation of CD8+ T cells
and epithelial cells, we evaluated the potential role of histamine in the release
of IL-16 into the airways of allergic asthmatics in vivo. METHODS: Eight allergic
asthmatic subjects, six normal subjects, and six atopic nonasthmatic subjects
were challenged with saline in the lingula and with serial concentrations of
histamine (1 x 10(-7) to 5 x 10(-5) mol/L) in the right middle lobe followed by
bronchoalveolar lavage (BAL) 15 minutes and 6 hours later. RESULTS: The BALF from
saline- and histamine-challenged lobes of normal subjects and atopic nonasthmatic
subjects contained no significant lymphocyte chemoattractant activity. In six of
the eight atopic asthmatic subjects, the histamine-challenged but not saline
challenged segment contained IL-16 chemotactic activity but no other identifiable
lymphocyte chemoattractant activities at 6 hours. CONCLUSIONS: IL-16 appears in
the airways after histamine challenge and therefore could contribute to the
earliest infiltration of CD4+ T cells and eosinophils observed after antigen
challenge due to histamine release from mast cells.
PMID- 9648707
TI - Ultrastructural analysis of human skin biopsy specimens from patients receiving
recombinant human stem cell factor: subcutaneous injection of rhSCF induces
dermal mast cell degranulation and granulocyte recruitment at the injection site.
AB - We performed an ultrastructural analysis of 10 skin biopsy specimens that had
been obtained from three women who were undergoing daily subcutaneous dosing with
recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I
clinical trial. The biopsy specimens were obtained at sites of subcutaneous
administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection,
and, at the same time, at contralateral control sites that had not been directly
injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF
in these subjects induced the local development of a wheal and flare response,
which was associated with evidence of mast cell degranulation, as well as a
systemic increase in numbers of cutaneous mast cells. The present electron
microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF
injected sites exhibited anaphylactic degranulation of both mature and immature
mast cells, an acute inflammatory response characterized by the migration of
neutrophils, basophils (some of which exhibited evidence of piecemeal
degranulation), and eosinophils through blood vessel walls into the perivascular
and extravascular spaces, and edema and fibrin deposition within the
interstitium. By contrast, the control biopsies contained no evidence of mast
cell degranulation or acute inflammation. However, both control and rhSCF
injected sites exhibited mast cells that were undergoing granule building and
maturation. Thus at the doses tested in these subjects, subcutaneous injection of
rhSCF induced anaphylactic-type degranulation of dermal mast cells at the
injection site, with an acute inflammatory response that was associated with the
recruitment of granulocytes. By contrast, mast cells at sites distant from those
directly injected with rhSCF exhibited no evidence of enhanced secretion.
PMID- 9648708
TI - Cloning and sequencing of a gene encoding a 2S albumin seed storage protein
precursor from English walnut (Juglans regia), a major food allergen.
AB - BACKGROUND: Walnuts rank third in per capita consumption of tree nuts in the
United States and can be associated with systemic IgE-mediated reactions in some
individuals. OBJECTIVE: The objectives of the study were to clone a gene encoding
one of the major food allergens in the walnut kernel and to characterize the
recombinant allergen. METHODS: A cDNA expression library in the lambda vector Uni
ZAP, which was prepared from walnut somatic embryos, was screened by using a
patient's sera that reacted with multiple protein bands on immunoblotting.
RESULTS: A cDNA clone containing an insert of 663 bp was identified and named Jug
r 1. DNA sequence analysis of this clone revealed that it encoded a protein 142
amino acids in length. Comparison of the encoded protein sequences with protein
databases revealed that this clone exhibits a 46.1% identity with the Brazil nut
(Bertholletia excelsa) methionine-rich 2S albumin seed storage protein precursor,
Ber e 1. Jug r 1 appears to be an important walnut food allergen; 12 of 16 sera
from patients allergic to walnuts demonstrated IgE binding to the 2S albumin seed
storage protein precursor fusion protein. An IgE-binding inhibition study
suggests that the walnut 2S protein precursor undergoes posttranslational
modification into a large and small subunit that is similar to castor seed,
cottonseed, mustard seed, and Brazil nut 2S seed storage protein allergens.
Interestingly, the gene encoding this allergenic protein in Brazil nuts has
recently gained notoriety because of its experimental use as a transgene to
enhance the nutritional quality of legumes. CONCLUSION: This is now the sixth
definitive 2S albumin seed storage protein demonstrated to bind IgE, suggesting
that this class of proteins is inherently allergenic.
PMID- 9648709
TI - Continued expression of anti-soy protein antibodies in rats bred on a soy protein
free diet for one generation: the importance of dietary control in oral
sensitization research.
AB - BACKGROUND: One of the major factors that may have negatively affected the
results of many oral sensitization studies in animals has been unscheduled
dietary preexposure of the test animals or their parental generations to the
antigen under investigation. OBJECTIVE: The influence of dietary preexposure to
soy protein on oral sensitization studies with soy protein in Brown Norway rats
was investigated. METHODS: Brown Norway rats bred on a soy protein-containing
diet for several generations (routine bred [RB] animals) were placed on a soy
protein-free diet during and for at least 6 months before breeding (F0 group).
Four generations of offspring were bred on a soy protein-free diet (F1, F2, F3,
and F4 groups). RB and F4 animals were exposed to soy protein either ad libitum
through drinking water or parenterally with an adjuvant. RESULTS: In the F0 and
F1 animals soy protein-specific IgG antibodies were still detectable, whereas no
soy protein-specific IgG was detectable in the other generations tested. In RB
animals no significant increase in soy protein-specific IgG titers occurred after
exposure to soy protein. Enteral exposure of the F4 animals to soy protein
resulted in sensitization to soy protein, with increased soy protein-specific IgG
titers. CONCLUSIONS: These studies demonstrate that there is a continued
expression of anti-soy protein antibodies in rats bred and raised on a soy
protein-free diet for one generation. Not only must the test animals be bred and
raised on a specified antigen-free diet, but their parental generations must also
be bred in the same manner to avoid any problems in oral sensitization studies.
PMID- 9648710
TI - A flow cytometric study about the immunopathology of vernal keratoconjunctivitis.
AB - BACKGROUND: Vernal keratoconjunctivitis (VKC) is a bilateral seasonal
conjunctival inflammation. Exact pathogenesis of the disease is unknown, but some
evidences suggest TH lymphocyte-mediated immune reactions. OBJECTIVE: The aim of
this study was to investigate the role of the T lymphocyte and its subsets in the
pathogenesis of VKC. METHODS: We obtained tear samples from patients with VKC and
normal volunteers during active (spring) and quiescent (winter) periods. The
patients' records were also obtained for assessment of symptom scores. The
percentages of CD4/29+, CD4/45RA+, CD4+, and CD8+ in tear samples were
established by using flow cytometry, and the results of all three groups were
compared with each other by using the Wilcoxon matched-pair signed-rank test and
the Mann-Whitney U test. RESULTS: The percentages of CD4/29+ and CD4+ cells in
tears of patients with VKC increased significantly in the active period and
decreased to normal levels in the quiescent stage. In contrast, the percentages
of CD4/45RA+ and CD8+ cells in tears of patients with VKC did not show any
significant change between spring and winter. The patients' symptoms were
significantly lower in the quiescent period (winter) compared with the active
stage (spring). CONCLUSION: We propose that increased numbers of CD4+ and CD4/29+
cells in tears may be exacerbating the disease during the spring season.
PMID- 9648711
TI - Proinflammatory cytokine-induced and chemical mediator-induced IL-8 expression in
human bronchial epithelial cells through p38 mitogen-activated protein kinase
dependent pathway.
AB - The p38 mitogen-activated protein (MAP) kinase is activated in various cells by
proinflammatory cytokines and environmental stresses. However, little is known
about the role of p38 MAP kinase in proinflammatory cytokine- and chemical
mediator-induced cytokine expression in human bronchial epithelial cells (BECs).
In this study we examined the role of p38 MAP kinase in IL-8 expression in BECs
to clarify the signal transduction pathway regulating IL-8 expression in BECs
stimulated with tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and platelet
activating factor (PAF). We used TNF-alpha, IL-1alpha, and PAF as inducers for
the analysis of the signal transduction pathway and determined IL-8 expression in
BECs because TNF-alpha, IL-1alpha, and PAF are known to induce cytokine
expression in BECs, and these proinflammatory cytokines and PAF are described to
have a role in the production of allergic inflammation. The results showed that
TNF-alpha, IL-1alpha, and PAF induced tyrosine phosphorylation of p38 MAP kinase
in a dose- and time-dependent manner. The specific p38 MAP kinase inhibitor, SB
203580, completely inhibited TNF-alpha-, IL-1alpha-, or PAF-induced IL-8 protein
and mRNA expression in BECs. These results indicated that p38 MAP kinase plays an
important role in TNF-alpha-, IL-1alpha-, or PAF-activated signaling pathway,
which regulates IL-8 expression in BECs. In addition, these results provide new
evidence on a strategy for treatment of airway inflammation with the specific p38
MAP kinase inhibitor.
PMID- 9648712
TI - Cloning of the American cockroach Cr-PII allergens: evidence for the existence of
cross-reactive allergens between species.
AB - BACKGROUND: Previously, we have identified the 28 and 32 kd proteins as
additional important allergens from the American cockroach (Periplaneta
americana) Cr-PII allergenic fraction. OBJECTIVE: The aim of this study was the
cloning of P. americana Cr-PII allergens. METHODS: A lambdagt22A cDNA library
constructed from P. americana mRNA was packaged into Escherichia coli Y1090 (r-),
and clones recognized by murine anti-Cr-PII monoclonal antibodies and human IgE
antibodies were isolated, sequenced, and subcloned into pET 21 and expressed in
E. coli BL21(DE3). RESULTS: Six Cr-PII-positive clones recognized by human IgE
antibodies were isolated. Two clones, C6 and C17, were sequenced, and we found
encoding proteins of 228 and 274 amino acids with no cysteine or any potential N
glycosylation site, with predicted masses of 25.8 and 31.14 kd, respectively.
Both molecules contain internal repeated sequences with a 94% identity between
them. C6 and C17 showed 59% and 77.3% skin reactivities, respectively, on 22
cockroach-sensitive atopic patients. Both clones were found to have 28.9% to
31.8% identities to ANG12 protein, a precursor of the African malaria mosquito
(Anopheles gambiae) and 82.7% to 85.1% identity to a nucleotide sequence of the
German cockroach (Blattella germanica) Bla g Bd90K allergen. The anti-C6 and anti
C17 antibodies were able to recognize Cr-PII, recombinant proteins, five
commercial American extracts, and two German cockroach extracts. Moreover, the
binding of anti-C6 and anti-C17 antibodies to recombinant protein can be
inhibited by B. germanica crude extract. Furthermore, Northern blot analyses have
shown that B. germanica mRNAs could be detected by both cDNA probes. CONCLUSION:
Our findings provide the first evidence of antigenic cross-reactivity between P.
americana and B. germanica allergens on molecular levels. The results will be a
great aid in facilitating the epitope mapping and improving diagnostic and
therapeutic reagents for both cockroach species.
PMID- 9648713
TI - T-lymphocyte responses to plicatic acid-human serum albumin conjugate in
occupational asthma caused by western red cedar.
AB - BACKGROUND: T cells are known to play a major role in the pathogenesis of atopic
allergic asthma, but it is less clear whether they are involved in occupational
asthma caused by low molecular weight chemicals such as plicatic acid.
OBJECTIVES: We sought to determine whether peripheral blood T cells from patients
with western red cedar asthma (WRCA) recognize plicatic acid (PA) conjugated to
human serum albumin (HSA) as judged by proliferation or cytokine production and
to analyze the response to PA inhalation with flow cytometry. RESULTS:
Significant proliferative responses to PA-HSA were observed in eight of 33
patients with WRCA, none of 10 exposed nonasthmatic cedar workers, and one of 18
nonasthmatic control subjects. Two of 25 patients with WRCA also showed
proliferative responses to unconjugated PA. All the WRCA responders were either
currently exposed to cedar or had ceased exposure within the preceding 2 years.
None of the four patients receiving oral steroids responded, but inhaled steroids
did not seem to influence responsiveness. No correlations were found between the
maximum stimulation response and any of the current FEV1 values, the current PC20
methacholine values, or the magnitude of the late asthmatic response to PA.
Peripheral blood T-cell subset proportions and their degree of activation were
similar in patients with WRCA and exposed control subjects. There was no change
in T-cell phenotypes or their activation markers after PA inhalation challenge.
In vitro, PA-HSA stimulation did not affect subset ratios but led to release of
small amounts of IL-5 and IFN-gamma, with no detectable increase in IL-4.
CONCLUSIONS: PA-HSA-specific T lymphocytes seem to be present in small numbers in
the peripheral blood of patients with WRCA and may respond to antigenic exposure
by producing IFN-gamma and IL-5. However, the proportion of responding cells
would appear to be lower than in comparable studies of atopic asthma.
PMID- 9648714
TI - Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody
immunodeficiency: use of an old method with a new product.
PMID- 9648715
TI - Food allergy to Boletus edulis.
PMID- 9648716
TI - Rickets associated with gastrointestinal disease in a patient with chronic
granulomatous disease.
PMID- 9648717
TI - Food-dependent exercise-induced anaphylaxis to corn.
PMID- 9648718
TI - Successful rush immunotherapy for anaphylaxis to imported fire ants.
PMID- 9648719
TI - Mechanisms of transcriptional regulation of gene expression in smooth muscle
cells.
PMID- 9648720
TI - Gene transfer into normal and atherosclerotic human blood vessels.
AB - Gene transfer to blood vessels is a promising new approach to the treatment of
the vascular diseases, but the feasibility of gene transfer to adult human
vessels has not been explored. We introduced an adenovirus vector encoding a
marker gene human placental alkaline phosphatase into normal and atherosclerotic
human vessels in organ culture. In the normal vessels, recombinant gene was
expressed preferentially in the endothelial cells (approximately 100%), intimal
smooth muscle cells (1.3+/-0.4%, 1.4+/-1.0%, and 3.8+/-0.8% in the internal
mammary arteries, saphenous veins, and normal coronary arteries, respectively),
and various adventitial cells. Advanced, complicated atherosclerotic plaques
demonstrated a similar efficiency of recombinant gene expression (3.1+/-0.5% and
3.8+/-0.3% of nonendothelial intimal cells in the coronary artery and carotid
artery plaques, respectively). Of these intimal cells, macrophages and smooth
muscle cells expressed a transgene, identifying them as targets for gene
transfer. Areas of plaque rupture and thrombus are sites of predilection for
expression of recombinant genes. Collagenase and elastase treatment increased the
percentage of transgenic alkaline phosphatase-positive cells 7 times (P<0.001),
suggesting that the pattern of gene expression was affected by the amount of
surrounding extracellular matrix. These studies demonstrate the feasibility of
gene transfer to human blood vessels. However, these studies also highlight
important barriers to adenoviral gene delivery to the actual normal and
atherosclerotic human vessels of clinical interest.
PMID- 9648721
TI - Acute host-mediated endothelial injury after adenoviral gene transfer in normal
rabbit arteries: impact on transgene expression and endothelial function.
AB - Acute injury after adenoviral vascular gene transfer remains incompletely
characterized. Here, we describe the early response (< or =days) in 52 New
Zealand White rabbits undergoing gene transfer (beta-galactosidase or empty
vector) or sham procedures to both carotid arteries. After gene transfer,
arteries were either left in vivo for 1 hour to 3 days (in vivo arteries) or were
excised immediately after gene transfer and cultured (ex vivo arteries). Within 1
hour, in vivo arteries receiving infectious titers of > or = 4X10(9) plaque
forming units (pfu)/mL showed endothelial activation, with an acute inflammatory
infiltrate developing by 6 hours. Ex vivo arteries showed endothelial activation
but no inflammatory infiltrate. There were also significant differences in
transgene expression between in vivo and ex vivo arteries. Ex vivo arteries
showed titer-dependent increases in beta-galactosidase expression through
2X10(10) pfu/mL, whereas in in vivo arteries, titers above 4X10(9) pfu/mL merely
increased acute inflammatory response, without increasing transgene expression.
In vivo arteries showed significant time- and titer-dependent impairment in
endothelium-dependent relaxation, with no effect on contraction or nitroprusside
induced relaxation. Interestingly, however, if rabbits were made neutropenic with
vinblastine, their arteries maintained full endothelium-dependent relaxation,
even after very high titer vascular infection (up to 1X10(11) pfu/mL). These
findings show that recombinant adenovirus triggers an early inflammatory
response, and it is the inflammatory response that in turn causes functional
endothelial injury. This occurs at much lower titers than previously appreciated
(though the precise threshold will undoubtedly vary between laboratories).
However, titers below the inflammatory threshold produce excellent transgene
expression without inflammation or vascular injury.
PMID- 9648722
TI - Role of nitric oxide in the control of renal oxygen consumption and the
regulation of chemical work in the kidney.
AB - Inhibition of NO synthesis has recently been shown to increase oxygen extraction
in vivo, and NO has been proposed to play a significant role in the regulation of
oxygen consumption by both skeletal and cardiac muscle in vivo and in vitro. It
was our aim to determine whether NO also has such a role in the kidney, a tissue
with a relatively low basal oxygen extraction. In chronically instrumented
conscious dogs, administration of an inhibitor of NO synthase, nitro-L-arginine
(NLA, 30 mg/kg i.v.), caused a maintained increase in mean arterial pressure and
renal vascular resistance and a decrease in heart rate (all P<0.05). At 60
minutes, urine flow rate and glomerular flow rate decreased by 44+/-12% and 45+/
7%, respectively; moreover, the amount of sodium reabsorbed fell from 16+/-1.7 to
8.5+/-1.1 mmol/min (all P<0.05). At this time, oxygen uptake and extraction
increased markedly by 115+/-37% and 102+/-34%, respectively (P<0.05). Oxygen
consumption also significantly increased from 4.5+/-0.6 to 7.1+/-0.9 mL O2/min.
Most important, the ratio of oxygen consumption to sodium reabsorbed increased
dramatically from 0.33+/-0.07 to 0.75+/-0.11 mL O2/mmol Na+ (P<0.05), suggesting
a reduction in renal efficiency for transporting sodium. In vitro, both a NO
donating agent and the NO synthase-stimulating agonist bradykinin significantly
decreased both cortical and medullary renal oxygen consumption. In conclusion, NO
plays a role in maintaining a balance between oxygen consumption and sodium
reabsorption, the major ATP-consuming process in the kidney, in conscious dogs,
and NO can inhibit mitochondrial oxygen consumption in canine renal slices in
vitro.
PMID- 9648723
TI - Angiotensin II stimulates p21-activated kinase in vascular smooth muscle cells:
role in activation of JNK.
AB - Angiotensin II (Ang II) has been previously shown to stimulate the extracellular
signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) mitogen
activated protein (MAP) kinase family members. Little is known regarding the
upstream signaling molecules involved in Ang II-mediated JNK activation. Ang II
has been shown to activate the Janus kinase/signal transducer(s) and activator(s)
of transcription (JAK/STAT) pathway, suggesting similarities to cytokine
signaling. In response to cytokines such as interleukin-1 and tumor necrosis
factor-alpha, the p21-activated kinase (PAK) has been identified as an upstream
component in JNK activation. Therefore, we hypothesized that PAK may be involved
in JNK activation by Ang II in vascular smooth muscle cells (VSMCs). AlphaPAK
activity was measured by myelin basic protein phosphorylation in rat aortic
VSMCs. In response to Ang II, alphaPAK was rapidly stimulated within 1 minute,
with a peak (5-fold increase) at 30 minutes. AlphaPAK stimulation preceded
activation of JNK in VSMCs. Ang II-mediated activation of both alphaPAK and JNK
was Ca2+ dependent and inhibited by downregulation of phorbol ester-sensitive
protein kinase C isoforms (by pretreatment with phorbol 12,13-dibutyrate) but not
by pretreatment with GF109203X. Activation of both PAK and JNK was partially
inhibited by tyrosine kinase inhibitors but not by specific Src inhibitors,
suggesting regulation by a tyrosine kinase other than c-Src. Finally,
introduction of dominant negative PAK markedly reduced the JNK activation by Ang
II in both Chinese hamster ovary and COS cells stably expressing the Ang II type
1 receptor (AT1R). Our data provide evidence for alphaPAK as an upstream mediator
of JNK in Ang II signaling and extend the role of Ang II as a proinflammatory
mediator for VSMCs.
PMID- 9648724
TI - Phosphorylation of p130Cas by angiotensin II is dependent on c-Src, intracellular
Ca2+, and protein kinase C.
AB - p130Cas is a signaling molecule that was initially found to be tyrosine
phosphorylated in v-Crk and v-Src transformed cells. We characterized the
regulation of p130Cas tyrosine phosphorylation in vascular smooth muscle cells by
angiotensin II (Ang II). This ligand induced a transient increase in p130Cas
tyrosine phosphorylation, which was sensitive to the actin polymerization
inhibitor cytochalasin D and to the intracellular Ca2+ chelator BAPTA-AM but not
the Ca2+ channel blocker verapamil. The Ang II-induced tyrosine phosphorylation
of p130Cas was also dependent on an active Src family tyrosine kinase, since it
could be blocked by the Src kinase inhibitors geldanamycin and PP1. Ang II
treatment resulted in the ability of p130Cas to bind at least 11 different
phosphate-containing proteins. Analysis of these proteins revealed that protein
kinase Calpha and the cell adhesion signaling molecule pp120 formed temporal
associations with p130Cas in response to Ang II. c-Src was found to associate
with p130Cas in a manner that was independent of Ang II treatment. Inhibition of
protein kinase C by either calphostin C or phorbol 12-myristate 13-acetate
downregulation inhibited the Ang II-induced tyrosine phosphorylation of p130Cas.
These results are the first to demonstrate that the tyrosine phosphorylation of
p130Cas by Ang II is transduced by the Src, intracellular Ca2+, protein kinase C
signaling pathway.
PMID- 9648725
TI - Overexpression of human superoxide dismutase inhibits oxidation of low-density
lipoprotein by endothelial cells.
AB - Oxidation of LDL in the subendothelial space has been proposed to play a key role
in atherosclerosis. Endothelial cells produce superoxide anions (O2.-) and
oxidize LDL in vitro; however, the role of O2.- in endothelial cell-induced LDL
oxidation is unclear. Incubation of human LDL (200 microg/mL) with bovine aortic
endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL
oxidation compared with cell-free incubation (22.5+/-1.1 versus 6.3+/-0.2 [mean+/
SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar
conditions, incubation of LDL with porcine aortic endothelial cells resulted in a
5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide
dismutase (Cu/ZnSOD, 100 microg/mL) in the medium reduced BAEC-induced LDL
oxidation by 79%. To determine whether the intracellular SOD content can have a
similar protective effect, BAECs were infected with adenoviral vectors containing
cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral
infection increased the content and activity of either Cu/ZnSOD or MnSOD in the
cells and reduced cellular O2.- release by two thirds. When cells infected with
AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was
decreased by 77% and 32%, respectively. Two other indices of LDL oxidation,
formation of conjugated dienes and increased LDL electrophoretic mobility, were
similarly reduced by SOD transduction. These data suggest that production of O2.-
contributes to endothelial cell-induced oxidation of LDL in vitro. Furthermore,
adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD,
effectively reduces oxidation of LDL by endothelial cells.
PMID- 9648726
TI - Superoxide production in vascular smooth muscle contributes to oxidative stress
and impaired relaxation in atherosclerosis.
AB - The endothelium is a source of reactive oxygen species in short-term models of
hypercholesterolemia and atherosclerosis. We examined a chronic model of
atherosclerosis for increased vascular production of superoxide (O2-.) and
determined whether endothelial overexpression of superoxide dismutase (SOD) would
improve endothelium-dependent relaxation. Superoxide generation was 3 times
higher in isolated aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits
(2 to 4 years old) compared with aortas from New Zealand White (NZ) rabbits (43+/
10 versus 14+/-2 relative light units x min(-1) x mm(-2), n=9, P<0.05). After in
vitro transduction with adenovirus containing the gene for CuZn-SOD (AdCMVCuZn
SOD) or extracellular SOD (AdCMVEC-SOD), endothelial O2-. levels in WHHL aortas
were significantly reduced. Gene transfer of SOD to WHHL aortas, however, failed
to improve the impaired relaxation to acetylcholine or calcium ionophore. By use
of the oxidative fluorescent dye hydroethidine, an in situ assay indicated
markedly increased generation of O2-. throughout the wall of WHHL aorta,
especially within layers of smooth muscle. This finding was confirmed by
demonstrating increased O2-. levels in smooth muscle cells cultured from WHHL
aorta. We conclude that elevated O2-. levels in atherosclerotic vessels are not
confined to the endothelium but occur throughout the vascular wall, including
smooth muscle cells. Reduction in endothelial O2-. levels is not sufficient to
improve endothelium-dependent relaxation. Generation of reactive oxygen species
within the media may contribute to vasomotor dysfunction in atherosclerosis.
PMID- 9648727
TI - Atypical protease-activated receptor mediates endothelium-dependent relaxation of
human coronary arteries.
AB - Protease-activated receptors (PARs) are a family of G protein-coupled receptors
activated by a tethered ligand sequence within the amino terminal that are
revealed by site-specific proteolysis. The thrombin-sensitive PAR-1 and trypsin
activated PAR-2 mediate endothelium-dependent vascular relaxation in a number of
species. Because both thrombin and trypsin-like enzymes have been implicated in
coronary artery disease, the purpose of this study was to investigate whether
similar receptors are present in human coronary arteries. Thrombin (0.001 to 0.1
U/mL) and trypsin (0.001 to 1 U/mL) caused concentration- and endothelium
dependent relaxations of human coronary artery ring segments suspended in organ
chambers for isometric tension recording and contracted with the thromboxane A2
mimetic U46619. These relaxations were dependent on the catalytic activity of
each enzyme and were inhibited by the NO synthase inhibitor NG-nitro-L-arginine
(100 micromol/L) and the NO scavenger oxyhemoglobin (20 micromol/L). The
synthetic PAR-1 tethered ligand sequence SFLLRN-NH2 (0.01 to 10 micromol/L) also
caused endothelium-dependent relaxation of U46619-contracted human coronary
arteries; however, the equivalent PAR-2 ligand SLIGKV-NH2 caused almost no
relaxation. In addition, desensitization to either thrombin or trypsin resulted
in cross-desensitization to the other enzyme but had only a minimal affect on the
response to SFLLRN-NH2. Therefore, we conclude that human coronary artery
endothelial cells possess a PAR-1-like receptor that is potently activated by
thrombin, trypsin, and SFLLRN-NH2 to cause NO-mediated vascular relaxation. Once
cleaved, this receptor is recycled in a truncated form, able to respond to
exogenous application of only its tethered ligand sequence, suggesting the
presence of another endogenous activator possibly acting independently of
receptor cleavage.
PMID- 9648728
TI - Autonomic control of vasomotion in the porcine coronary circulation during
treadmill exercise: evidence for feed-forward beta-adrenergic control.
AB - To date, no studies have investigated coronary vasomotor control of myocardial O2
delivery (MDO2) and its modulation by the autonomic nervous system in the porcine
heart during treadmill exercise. We studied 8 chronically instrumented swine
under resting conditions and during graded treadmill exercise. Exercise up to 85%
to 90% of maximum heart rate produced an increase in myocardial O2 consumption
(MVO2) from 163+/-16 micromol/min (mean+/-SE) at rest to 423+/-75 micromol/min
(P< or =0.05), which was paralleled by an increase in MDO2, so that myocardial O2
extraction (79+/-1% at rest) and coronary venous O2 tension (cvPO2, 23.7+/-1.0 mm
Hg at rest) were maintained. Beta-adrenoceptor blockade blunted the exercise
induced increase of MDO2 out of proportion compared with the attenuation of the
exercise-induced increase in MVO2, so that O2 extraction rose from 78+/-1% at
rest to 83+/-1% during exercise and cvPO2 fell from 23.5+/-0.9 to 19.6+/-1.1 mm
Hg (both P< or =0.05). In contrast, alpha-adrenoceptor blockade, either in the
absence or presence of beta-adrenoceptor blockade, had no effect on myocardial O2
extraction or cvPO2 at rest or during exercise. Muscarinic receptor blockade
resulted in a decreased O2 extraction and an increase in cvPO2 at rest, an effect
that waned during exercise. The vasodilation produced by muscarinic receptor
blockade was likely due to an increased beta-adrenoceptor activity, since
combined muscarinic and beta-adrenoceptor blockade produced similar changes in O2
extraction and cvPO2, as did beta-adrenoceptor blockade alone. In conclusion, in
swine myocardium, MVO2 and MDO2 are matched during exercise, which is the result
of feed-forward beta-adrenergic vasodilation in conjunction with minimal a
adrenergic vasoconstriction. Beta-adrenergic vasodilation is due to an increase
in sympathetic activity but may also be supported by withdrawal of muscarinic
receptor-mediated inhibition of beta-adrenergic coronary vasodilation. The
observation that cvPO2 levels are maintained even during heavy exercise suggests
that a decrease in cvPO2 is not essential for coronary vasodilation during
exercise.
PMID- 9648729
TI - Nitric oxide inhibits alpha2-adrenoceptor-mediated endothelium-dependent
vasodilation.
AB - This study was designed to investigate the interaction between the NO/L-arginine
pathway and the alpha2-adrenoceptor-mediated endothelium-dependent
vasorelaxation. Reactivity of isolated resistance mesenteric arterial segments
from mice lacking the gene for constitutive endothelial NO synthase (eNOS- mice,
n=14) and from their wild-type controls (WT mice, n=46) was studied in isometric
conditions in the presence of indomethacin (blocker of cyclooxygenase).
Oxymetazoline (OXY, 0.01 to 30 micromol/L; a selective alpha2-adrenoceptor
agonist) induced an endothelium-dependent relaxation of eNOS- but not WT arteries
preconstricted either with phenylephrine or serotonin. In the presence of Nomega
nitro-L-arginine (l-NNA, 100 micromol/L), an inhibitor of NOS, OXY induced an
endothelium-dependent relaxation of WT mesenteric arteries. l-NNA had no effect
on the relaxation caused by OXY in eNOS- arterial rings. Therefore, the
relaxation caused by OXY was independent of NO formation. To demonstrate the
inhibitory role of NO on the alpha2-adrenoceptor-mediated relaxation,
subthreshold (0.1 nmol/L) to threshold (1 nmol/L) concentrations of sodium
nitroprusside (donor of NO) were added to l-NNA-treated arteries before OXY
challenges: in these conditions, the alpha2-adrenoceptor-mediated relaxation of
eNOS- and WT arteries was inhibited. OXY-induced relaxation was restored on
readdition of methylene blue (1 micromol/L, inhibitor of guanylate cyclase),
suggesting that cGMP may be the mechanism of inhibition of the alpha2-adrenergic
pathway in the presence of NO. Finally, OXY-mediated relaxation was blocked by
tetraethylammonium (1 mmol/L) but not glibenclamide (1 micromol/L), suggesting
the involvement of an endothelium-derived hyperpolarizing factor that activates
Ca2+-activated K+ channels. In conclusion, alpha2-adrenoceptor activation caused
relaxation of isolated murine mesenteric arteries that was functionally blocked
by NO through a mechanism that may involve activation of the soluble guanylate
cyclase and cGMP formation. The endothelium-dependent alpha2-adrenoceptor
mediated relaxation is likely to be due to an endothelium-derived hyperpolarizing
factor, whose release and/or production is reduced by concurrent NO formation.
PMID- 9648730
TI - Increase in functional Ca2+ channels in cerebral smooth muscle with renal
hypertension.
AB - The hypothesis that availability of functional Ca2+ channels in vascular smooth
muscle is augmented in hypertension was tested in basilar artery cells from
Wistar rats exhibiting stable systolic blood pressure (BPsys) for 2 to 11 weeks
after partial renal artery ligation (Goldblatt 2-kidney 1-clip [2K1C] model).
Cells were freshly isolated and patch-clamped using a nystatin-perforated patch
method. BPsys ranged from 110 to 280 mm Hg and correlated with normalized kidney
mass. Macroscopic current-voltage curves were fit to a Boltzmann function to
obtain maximum conductance (gmax), steepness and midpoint potential for the
voltage dependence of activation (k and E1/2, respectively), and extrapolated
reversal potential for the chord conductance (Erev). Linear regression of
normalized conductance (ng(max)=g(max)/cell capacitance) versus BPsys for 103
cells indicated a strong relationship, with a slope of 0.0019 nS x pF(-1) x mm
Hg(-1) (P<0.0001). Similar analysis of data from 35 other cells exposed to 500
nmol/L Bay K 8644 gave a slope of 0.0041 nS x pF(-1) x mm Hg(-1) (P=0.001).
Voltage-dependent parameters, k, E1/2, and Erev, were not significantly related
to BPsys. Single-channel measurements in cell-attached patches revealed that the
number of channels in 32 patches was significantly related to BPsys (P=0.0024)
but that slope conductance, open dwell times at 0 mV, and distribution between 2
open states were not. Finally, in a subgroup of 61 cells from animals made
hypertensive (180 mm Hg150 micromol/l), and four patients
were undergoing renal dialysis. Indications for stenting were recoil after
percutaneous transluminal angioplasty (n = 12), arterial dissection after
angioplasty (n = 2), restenosis after angioplasty (n = 1), and as the primary
intervention (n = 6). Follow-up angiography was performed in 16 patients (76%).
RESULTS: Initial technical success was achieved in all patients (residual
stenosis, <5%). At follow-up (range, 6-25 months), renal function had returned to
normal in five patients (24%), improved in four patients (19%), stabilized in six
patients (29%), and deteriorated in six patients (29%). Dialysis has been
discontinued in all four dialysis patients. Major complications occurred in four
patients (19%), including one death within 30 days of stenting. No significant
restenoses were seen on follow-up angiography. CONCLUSION: Placement of renal
artery stents in the solitary kidney led to benefits in 70% of patients treated,
including improved renal function in nine patients (43%) and stabilization in six
patients (29%). In this high-risk group of patients, we advocate renal artery
stenting as a relatively safe procedure to salvage the solitary kidney.
PMID- 9648793
TI - Gradient-echo versus fat-suppressed fast spin-echo MR imaging of rotator cuff
tears.
AB - OBJECTIVE: The purpose of this study is to compare fat-suppressed T2-weighted
fast spin-echo sequences with T2-weighted multiplanar gradient-echo sequences in
revealing rotator cuff disorders. MATERIALS AND METHODS: Oblique coronal fat
suppressed fast spin-echo images and gradient-echo images of 39 patients who
underwent surgery of the shoulder were retrospectively reviewed. Images from the
two techniques were reviewed separately. Each set of images was interpreted twice
by four musculoskeletal radiologists independently and without knowledge of the
surgical findings. Sensitivity and specificity for both sequences were
determined. The kappa statistic was used to calculate intraobserver and
interobserver agreement of interpretations. RESULTS: For detecting any tear, the
sensitivity of the four readers was 71-96% using fast spin-echo and 58-100% using
gradient-echo imaging. Confidence intervals showed no difference between the two
sequences. Sensitivity of detecting full-thickness tears was 83-100% for both
sequences. Interobserver agreement was good. CONCLUSION: T2-weighted gradient
echo and fat-suppressed T2-weighted fast spin-echo sequences depict rotator cuff
tears equally well and take less time to acquire than conventional dual-echo spin
echo sequences.
PMID- 9648794
TI - The association between irregular greater tuberosities and rotator cuff tears: a
sonographic study.
AB - OBJECTIVE: Although an association between irregular greater tuberosities and
rotator cuff tears has been suggested, no formal studies have been done. This
study was designed to investigate the relationship between greater tuberosity
irregularities, rotator cuff tears, and age. SUBJECTS AND METHODS: Sonographic
examinations of both shoulders of 77 asymptomatic individuals (154 shoulders)
between 30 and 80 years old were performed. The rotator cuffs and greater
tuberosities were evaluated. Full- and partial-thickness rotator cuff tears were
given equal significance. A two-tailed Fisher's exact test, a Student's t test,
and logistic regression analysis were used to analyze the data. RESULTS:
Sonography showed the greater tuberosity to be irregular in 36 (90%) of 40
shoulders with a rotator cuff tear. The greater tuberosity was irregular in only
12 (11%) of 114 shoulders without a rotator cuff tear. When the greater
tuberosity was irregular, sonography showed 36 (75%) of 48 shoulders to have
rotator cuff tears. When the greater tuberosity was normal, 102 (96%) of 106 of
the rotator cuffs were normal on sonography. Statistical significance was
detected (p < .001) for the association of greater tuberosity irregularity and
rotator cuff tear. After accounting for age, a statistically significant
association was found (p < .001) between rotator cuff status and greater
tuberosity status. CONCLUSION: On sonography, greater tuberosity irregularities
are reliable indicators in the assessment of shoulders for rotator cuff tears. In
addition, we have shown that greater tuberosity irregularities are not simply
related to aging.
PMID- 9648795
TI - Anatomy, anatomic variations, and pathology of the 11- to 3-o'clock position of
the glenoid labrum: findings on MR arthrography and anatomic sections.
PMID- 9648796
TI - Three-dimensional MR arthrography of the shoulder: an intraarticular perspective.
PMID- 9648797
TI - Traumatic elbow effusions in pediatric patients: are occult fractures the rule?
AB - OBJECTIVE: Elbow joint effusion with no fracture seen on radiographs of pediatric
patients after acute trauma has become synonymous with occult fracture. This
study evaluates the incidence of occult fractures in such cases as determined by
findings on follow-up radiographs. MATERIALS AND METHODS: Initial and follow-up
radiographs were reviewed for 54 children (mean age, 7 years) with a history of
trauma who had joint effusion but no identifiable fracture on initial
radiographs. The presence of periosteal reaction or bony sclerosis on follow-up
radiographs was considered to be evidence of occult fracture. Mean time between
initial and follow-up radiographs was 18 days (range, 14-50 days). RESULTS: Only
nine (17%) of the 54 patients showed evidence of a healing occult fracture on
follow-up radiographs. However, we found a statistically significant relationship
(p = .001) between persistent joint effusion on follow-up radiographs and occult
fracture. Seventy-eight percent of cases with occult fracture, versus 16% of
cases without occult fracture, had persistent effusions. CONCLUSION: Joint
effusion without visualized fracture on initial radiographs after trauma does not
correlate with the presence of occult fracture in most cases (83%). Therefore,
joint effusion as revealed by radiography should not be considered synonymous
with occult fracture.
PMID- 9648798
TI - Soft-tissue hemangiomas in infants and children: diagnosis using Doppler
sonography.
AB - OBJECTIVE: We describe the sonographic appearance and vascularization of
hemangiomas and determine if vessel density and peak systolic Doppler shifts
distinguish hemangiomas from other superficial soft-tissue masses. SUBJECTS AND
METHODS: Our pilot study included 20 infants and children with hemangiomas who
were to undergo biopsy before treatment with interferon alpha-2b. We used Doppler
sonography to determine the number of vessels per square centimeter, peak
arterial Doppler shift, resistive index, and signs of arteriovenous shunting. All
hemangiomas showed high vessel density (more than five per square centimeter) and
high Doppler shifts (more than 2 kHz), and these two factors became our
diagnostic criteria. A prospective study of 116 patients was then carried out.
One hundred sixteen consecutive pediatric patients with superficial soft-tissue
masses were examined using Doppler sonography; sonographic findings were compared
with the final diagnoses that were established by biopsy, CT, or clinical follow
up. RESULTS: The final diagnoses included 70 hemangiomas, 20 venous
malformations, three arteriovenous malformations, three arteriolocapillary
malformations, and 20 other masses. Fifty-nine lesions showing high vessel
density (more than five per square centimeter) and a peak arterial Doppler shift
exceeding 2 kHz were correctly diagnosed as hemangiomas (sensitivity, 84%;
specificity, 98%). One arteriovenous malformation showed high vessel density and
high Doppler shifts, but none of the other masses that were not hemangiomas did.
Eleven patients with hemangiomas who were being treated with interferon at the
time of the study fulfilled only one of the two diagnostic criteria. CONCLUSION:
High vessel density and high peak arterial Doppler shift can be used to
distinguish hemangiomas from other soft-tissue masses.
PMID- 9648799
TI - Cavitary necrosis complicating pneumonia in children: sequential findings on
chest radiography.
AB - OBJECTIVE: The objective of this study was to describe the sequential clinical
and radiographic findings of cavitary necrosis complicating pneumonia in
childhood. MATERIALS AND METHODS: A study group of 17 children (mean age, 6
years) was identified by reviewing CT examinations of all patients who underwent
CT of the chest to evaluate possible complications of pneumonia over a 3-year
period. Children included in the study group were those who met the criteria for
cavitary necrosis: loss of lung architecture, decreased enhancement, and multiple
cavities with thin, nonenhancing walls. In the 17 identified cases, sequential
chest radiographs were reviewed for visibility of a lung cavity. Long-term follow
up radiographs were evaluated for persistent abnormalities. RESULTS: Ten of the
17 cases of cavitary necrosis seen on CT showed cavities at some time on
radiography: one cavity was visible at the time of diagnosis on CT and nine were
visible only later. All three cavities that were predominantly air-filled on CT
were revealed by radiography, whereas 50% (7/14) of predominantly fluid-filled
cavities were revealed by radiography. Eleven children underwent follow-up
radiography more than 40 days after the diagnosis of cavitary necrosis.
Radiographs of those 11 children showed clear lungs without pulmonary sequelae.
CONCLUSION: In children, cavitary necrosis is associated with severe illness;
however, cases usually resolve without surgical intervention, and long-term
follow-up radiography shows clear lungs without pulmonary sequelae. Evidence of
cavitary necrosis complicating pneumonia is often seen on CT before or in the
absence of findings on chest radiography.
PMID- 9648800
TI - Radiologic placement of long-term subcutaneous venous access ports in children.
AB - OBJECTIVE: The purpose of this study was to review the results of radiologically
placed subcutaneous venous access ports in a pediatric population requiring long
term venous access. CONCLUSION: Sixteen of 20 patients had no significant
problems with their ports. In the pediatric population, radiologically placed
subcutaneous venous access ports offer a high success rate, a low complication
rate, and significant cost savings over surgically placed ports.
PMID- 9648801
TI - Hemoptysis during lung biopsy after aspirin.
PMID- 9648802
TI - Bone marrow abnormalities revealed by MR imaging.
PMID- 9648803
TI - Callback rate after screening mammography.
PMID- 9648804
TI - T2-weighted fast spin-echo MR imaging of liver.
PMID- 9648805
TI - Ketamine hydrochloride for interventional radiology in children: is it sedation
or anesthesia by the radiologist?
PMID- 9648806
TI - The "R" word: unfortunately, the mammography war is not yet over.
PMID- 9648807
TI - Reducing headaches after a myelogram.
PMID- 9648808
TI - Current concepts in osteoporosis: theoretic rather than practical.
PMID- 9648809
TI - Can patient retention of rectal barium be guaranteed?
PMID- 9648810
TI - Problematic p values.
PMID- 9648811
TI - Concerning the National Breast and Cervical Cancer Early Detection Program.
PMID- 9648812
TI - Metallic particles on mammography.
PMID- 9648813
TI - Epidermoid cyst in an intrapancreatic accessory spleen: CT and pathologic
findings.
PMID- 9648814
TI - Helical CT of a patient with suspected renal colic: a new protocol consideration.
PMID- 9648815
TI - Extensive esophageal pneumatosis after acute dilatation of the stomach.
PMID- 9648816
TI - Term pregnancy in a patient with McKusick-Kaufman syndrome.
PMID- 9648817
TI - Multicentric granulocytic sarcoma of the breast: mammographic and sonographic
findings.
PMID- 9648818
TI - Neurosarcoidosis mimicking a cerebellopontine angle meningioma.
PMID- 9648819
TI - Endovascular retrieval of an embolized central venous catheter in a neonate of
very low birth weight.
PMID- 9648820
TI - Autonomic mediation of glucagon secretion during hypoglycemia: implications for
impaired alpha-cell responses in type 1 diabetes.
AB - This article examines the role of the autonomic nervous system in mediating the
increase of glucagon secretion observed during insulin-induced hypoglycemia
(IIH). In the first section, we briefly review the importance of the alpha-cell
response in recovery from hypoglycemia under both physiologic conditions and
pathophysiologic conditions, such as type 1 diabetes. We outline three possible
mechanisms that may contribute to increased glucagon secretion during
hypoglycemia but emphasize autonomic mediation. In the second section, we review
the critical experimental data in animals, nonhuman primates, and humans
suggesting that, in the absence of diabetes, the majority of the glucagon
response to IIH is mediated by redundant autonomic stimulation of the islet alpha
cell. Because the glucagon response to hypoglycemia is often impaired in patients
with type 1 diabetes, in the third section, we examine the possibility that
autonomic impairment contributes to the impairment of the glucagon response in
these patients. We review two different types of autonomic impairment. The first
is a slow-onset and progressive neuropathy that worsens with duration of
diabetes, and the second is a rapid-onset, but reversible, autonomic dysfunction
that is acutely induced by antecedent hypoglycemia. We propose that both types of
autonomic dysfunction can contribute to the impaired glucagon responses in
patients with type 1 diabetes. In the fourth section, we relate restoration of
these glucagon responses to restoration of the autonomic responses to
hypoglycemia. Finally, in the fifth section, we summarize the concepts underlying
the autonomic hypothesis, the evidence for it, and the implications of the
autonomic hypothesis for the treatment of type 1 diabetes.
PMID- 9648821
TI - Constitutive activation of protein kinase B alpha by membrane targeting promotes
glucose and system A amino acid transport, protein synthesis, and inactivation of
glycogen synthase kinase 3 in L6 muscle cells.
AB - Phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated in the regulation
of numerous cellular processes, including the insulin-induced regulation of
glycogen synthase kinase 3 (GSK-3) and glucose transport. The hormonal-induced
inactivation of GSK-3 is mediated by protein kinase B (PKB), a downstream target
of PI 3-kinase, whose involvement in other insulin-stimulated responses remains
poorly defined at present. In this study, we investigated whether the uptake of
glucose, system A amino acid transport, and cellular protein synthesis are
regulated by PKBalpha in L6 skeletal muscle cells. L6 cells stably overexpressing
wild-type PKBalpha (wtPKBalpha) or a constitutively active membrane-targeted
PKBalpha (mPKBalpha) showed a 3- and 15-fold increase in PKB activity,
respectively. Both wtPKBalpha and mPKBalpha expression led to a significant
increase in the basal uptake of glucose and methyl-aminoisobutyric acid (a
substrate for the system A amino acid transporter), at least to a level seen in
control cells treated with insulin. The stimulation in glucose transport was
facilitated, in part, by the increased translocation of GLUT4 to the plasma
membrane and also through an increase in the cellular synthesis of GLUT3. In the
absence of insulin, only muscle cells expressing the constitutively active
PKBalpha showed a significant increase in protein synthesis and an inhibition in
GSK-3. Our results indicate that constitutive activation of PKBalpha in skeletal
muscle stimulates the uptake of glucose, system A amino acids, and protein
synthesis and promotes the inactivation of GSK-3. These observations imply that
PKBalpha may have a role in the insulin-regulated control of these processes in
skeletal muscle.
PMID- 9648822
TI - Chronic central leptin infusion enhances insulin-stimulated glucose metabolism
and favors the expression of uncoupling proteins.
AB - Continuous (4 days) intracerebroventricular leptin infusion (12 microg/day) was
performed in lean rats, and its hormonometabolic effects were determined.
Intracerebroventricular leptin administration did not result in leakage of the
hormone into the peripheral circulation. Thus, its effects were elicited by its
presence within the central nervous system. Intracerebroventricular leptin
infusion produced marked decreases in food intake and body weight gain relative
to vehicle-infused fed ad libitum rats. Because decreases in food intake alter
hormonometabolic homeostasis, additional control rats pair-fed to the amount of
food consumed by leptin-infused ones were included in the study.
Intracerebroventricular leptin-infused and vehicle-infused pair-fed rats were
characterized, relative to vehicle-infused ad libitum-fed animals, by decreases
in body weight and insulinemia and by increases in insulin-stimulated overall
glucose utilization and muscle and brown adipose tissue glucose utilization
index. Brown adipose tissue uncoupling protein (UCP)1, UCP2, and UCP3 mRNA levels
were markedly decreased in pair-fed animals relative to those of fed ad libitum
control animals, as were liver and white adipose tissue UCP2 and muscle UCP3 mRNA
levels. In marked contrast, intracerebroventricular leptin administration was
accompanied by the maintenance of high UCP1, UCP2, and UCP3 expression in all
these tissues. Thus, despite analogies between leptin's effects and those of pair
feeding with regard to glucose handling, their respective underlying mechanisms
differ. While leptin maintains or favors energy-dissipating mechanisms (UCP1,
UCP2, and UCP3), the latter are markedly depressed in pair-fed rats. This effect
of leptin may prevent subsequent excessive storage processes, thereby maintaining
normal body homeostasis.
PMID- 9648823
TI - Glucose turnover and insulin sensitivity in rats with pancreatic islet
transplants.
AB - To study the metabolic effects of insulin derived from islet grafts, oral glucose
tolerance (OGT) and glucose turnover were examined in streptozotocin-induced
diabetic Lewis rats rendered normoglycemic by syngeneic islet grafts in the renal
subcapsular space (REN), in REN with renal vein-to-mesenteric vein anastomosis
(REN-RMA), in the liver (intrahepatic [IH]), or in a parahepatic omental pouch
(POP) and compared with normal rats. Normal OGT was found at 1 month
posttransplant in all animals receiving approximately 3,000 islets, with
hyperinsulinemic responses in the REN group compared with the other groups, and
with higher C-peptide responses in the IH group than in the other groups (P <
0.05 by one-way analysis of variance). Glucose turnover studies in the insulin
stimulated steady state (INS-SS; infusion of insulin at 10 pmol x kg(-1) x min(
1)) at 2 months posttransplant showed that whole body glucose disappearance rates
(Rd) were similar in all groups, but the REN group had higher steady-state
insulin levels than the other groups. Glucose infusion rates (GIRs) were lower in
the REN and IH groups than in the other groups. Apparent endogenous glucose
production (EGP) was not completely inhibited in the REN and IH groups, while
complete inhibition was observed in the other groups. When INS-SS insulin levels
were matched to the level in REN rats by increasing the insulin infusion rate to
20 pmol x kg(-1) x min(-1) in REN-RMA, IH, and normal rats, GIR and Rd were
elevated, exceeding those values in REN rats, but GIR in IH rats was still lower
than in REN-RMA and normal rats. Thus, 1) in the REN group, impairment of
inhibition of EGP and of stimulation of Rd by exogenous insulin contribute to
insulin resistance; 2) in the IH group, incomplete inhibition of EGP is the major
determinant of insulin resistance; and 3) with portal delivery of insulin in the
REN-RMA and POP groups, normal insulin sensitivity is preserved. The present
study confirms that hepatic portal delivery of islet secretions is necessary for
physiological regulation of glucose metabolism. The study also suggests the IH
grafts do not provide physiological regulation of glucose metabolism, raising the
question of whether the liver is an appropriate site for insulin-secreting tissue
replacement therapy in diabetes.
PMID- 9648824
TI - Measurements of oxygen tension in native and transplanted rat pancreatic islets.
AB - This study was performed to measure the oxygen tension before and after
revascularization of pancreatic islets transplanted beneath the renal capsule and
to investigate to what extent this was affected by acute and chronic
hyperglycemia. In addition, the oxygen tension in islets within the pancreas was
determined. PO2 was measured with a modified Clark electrode (tip 2-6 microm
o.d.). Within native pancreatic islets, the mean PO2 was higher (31-37 mmHg) than
within the exocrine pancreas (20-23 mmHg). The mean oxygen tension in the
transplanted islets the day after implantation was half of that recorded in
native islets (14-19 mmHg) and did not differ between normoglycemic and diabetic
recipients. At 1 month after transplantation, when revascularization had
occurred, the mean PO2 in the islet grafts was 9-15 mmHgf in normoglycemic
animals but was lower (6-8 mmHg) in diabetic animals, whereas the blood perfusion
of the transplants, as measured with laser-Doppler flowmetry (probe diameter 0.45
mm), was similar in both groups. The mean oxygen tension in the superficial renal
cortex surrounding the implanted islets was similar in all groups and remained
stable at 13-21 mmHg. Intravenous administration of D-glucose (1 g/kg) did not
affect the oxygen tension in any of the investigated tissues. We conclude that
the mean PO2 in islets implanted under the renal capsule is markedly lower than
in native islets, not only in the immediate posttransplantation period but also 1
month after implantation, i.e., when revascularization has occurred. Furthermore,
persistent hyperglycemia in the recipient leads to a further decrease in graft
oxygen tension. To what extent this may contribute to islet graft failure is at
present unknown.
PMID- 9648825
TI - Sex difference in resistance to dexamethasone-induced apoptosis in NOD mice:
treatment with 1,25(OH)2D3 restores defect.
AB - The NOD mouse, a model for type 1 diabetes, is characterized by resistance to
apoptosis in immunocytes. The aim of this study was to investigate a link between
apoptosis in NOD thymocytes and autoimmunity. First, we demonstrated that the
sexual dimorphism in diabetes incidence in NOD mice (females are more diabetes
prone than males) is reflected by differences in apoptosis. Apoptosis in NOD
thymocytes, 24 h after dexamethasone, was decreased in both sexes compared with
C57B1/6, but it was lower in female mice (26 +/- 2%) than in male mice (50 +/-
3%, P < 0.001). Further, we demonstrated that sex hormones themselves play a
central role in this difference, since castration of NOD male mice, which
increases diabetes incidence, decreased apoptosis levels (32 +/- 2%), while
treatment of NOD female mice with dihydrotestosterone, which protects against
diabetes, restored apoptosis to male levels (42 +/- 1.5%). Finally, we
demonstrated that 1,25-dihydroxyvitamin D3, a steroid hormone that prevents
diabetes in NOD mice, restored apoptosis levels to C57B1/6 reference levels. This
improved apoptosis was seen in male (68 +/- 1 vs. 50 +/- 3% in untreated NOD
mice, P < 0.001) but especially in female NOD mice (51 +/- 5 vs. 26 +/- 2% in
untreated NOD mice, P < 0.001). Fluorescence-activated cell sorter analysis of
thymocyte subsets revealed marked differences, especially in CD4+CD8+ and CD4+
cells. We conclude that the sexual dimorphism in diabetes incidence in NOD mice
is paralleled by a dimorphism in resistance to apoptotic signals in NOD
thymocytes. This resistance to apoptosis is driven by sex hormones and is
corrected by 1,25-dihydroxyvitamin D3.
PMID- 9648826
TI - Peptones stimulate both the secretion of the incretin hormone glucagon-like
peptide 1 and the transcription of the proglucagon gene.
AB - Truncated glucagon-like peptide (GLP)-1 is a potent incretin. Its synthesis and
secretion are modulated by food, but the influence of individual nutrients
remains to be established. The hypothesis that protein hydrolysates (peptones)
can directly regulate both GLP-1 secretion and proglucagon (PG) gene
transcription was tested in this study, ex vivo in the isolated vascularly
perfused rat intestine and in vitro in the murine enteroendocrine cell line STC
1. Peptones were albumin egg hydrolysate (AEH) and meat hydrolysate (MH). We
demonstrate in these two models that peptones dose-dependently stimulate GLP-1
release, whereas isocaloric quantities of bovine serum albumin or of an amino
acid mixture had no stimulatory effect. A strong and rapid increase of PG RNA
level was observed in STC-1 cells treated with peptones (14-fold and 7-fold
increase after 4 h of incubation with 3% wt/vol MH and AEH, respectively).
Peptones also increased the PG RNA level in the colonic PG-expressing cell line
GLUTag. In contrast, peptones did not modify the PG RNA level in two pancreatic
glucagon-producing cell lines, namely, the RINm5F and INR1G9 cells. The peptone
effect in STC-1 cells was completely abolished by blocking transcription before
MH treatment. The stability of proglugacon transcripts was not modified by MH
treatment, but nascent transcripts were more abundant in STC-1 cells preincubated
with MH. Finally, MH treatment strongly stimulated (15-fold stimulation) the
transcriptional activity of two PG gene promoter fragments (-1100 and -350 base
pair) linked to the CAT reporter gene transiently transfected in STC-1 cells.
Overall, peptones evoke an as yet undescribed release of GLP-1 when brought into
contact with native intestinal L-cells or with STC-1 enteroendocrine cells. The
increased transcription of the glucagon gene in the latter system suggests an
important role of protein hydrolysates in the control of not only the secretion
but also the synthesis of the incretin hormone.
PMID- 9648827
TI - Enhanced glucose-dependent insulinotropic polypeptide secretion and
insulinotropic action in glucagon-like peptide 1 receptor -/- mice.
AB - Incretins are gastrointestinal hormones that act on the pancreas to potentiate
glucose-stimulated insulin secretion. Despite the physiological importance of the
enteroinsular axis, disruption of glucagon-like peptide (GLP)-1 action is
associated with only modest glucose intolerance in GLP-1 receptor -/- (GLP-1R -/
) mice. We show here that GLP-1R -/- mice exhibit compensatory changes in the
enteroinsular axis via increased glucose-dependent insulinotropic polypeptide
(GIP) secretion and enhanced GIP action. Serum GIP levels in GLP-1R -/- mice were
significantly elevated versus those in +/+ control mice after an oral glucose
tolerance test (369 +/- 40 vs. 236 +/- 28 pmol/l; P < or = 0.02). Furthermore,
GIP perfusion of mice pancreas and isolated islets in the presence of elevated
glucose concentrations elicited a significantly greater insulin response in GLP
1R -/- than in +/+ mice (P < or = 0.02-0.05). In contrast, no significant
perturbation in the insulin response to perfused glucagon was detected under
conditions of low (4.4 mmol/l) or high (16.6 mmol/l) glucose in GLP-1R -/- mice.
Total pancreatic insulin but not glucagon content was significantly reduced in
GLP-1R -/- compared with in +/+ mice (77 +/- 9 vs. 121 +/- 10 pmol/mg protein; P
< or = 0.005). These observations suggest that upregulation of the GIP component
of the enteroinsular axis, at the levels of GIP secretion and action, modifies
the phenotype resulting from interruption of the insulinotropic activity of GLP-1
in vivo.
PMID- 9648829
TI - Pancreatic beta-cell regeneration after 48-h glucose infusion in mildly diabetic
rats is not correlated with functional improvement.
AB - We investigated the effect of glucose infusion on beta-cell regeneration in rats
made mildly diabetic by a single injection of low dosage (35 mg/kg)
streptozotocin (STZ). Nondiabetic (ND) and STZ rats were submitted to a 48-h
glucose infusion (hyperglycemia approximately 22 mmol/l in both groups: ND and
STZ hyperglycemic-hyperinsulinemic [ND HG-HI and STZ HG-HI rats]). Before
infusion, beta-cell mass was 65% lower in STZ rats than in ND rats (2.0 +/- 0.02
vs. 5.5 +/- 0.6 mg), 1.6-fold increased in ND HG-HI rats (8.7 +/- 1.7 mg), and
2.7-fold increased in STZ HG-HI rats (5.4 +/- 0.9 mg). In ND HG-HI rats, beta
cell enlargement was related to an increase in beta-cell responsiveness to
nutrient secretagogues both in vivo and in vitro, whereas in STZ HG-HI rats, no
significant improvement in insulin secretion could be noticed. To determine the
respective role of hyperglycemia and hyperinsulinemia on beta-cell area changes,
ND and STZ rats were submitted to a 48-h hyperinsulinemic-euglycemic clamp. No
modification of beta-cell mass was detected in either group. In conclusion, 48-h
superimposed hyperglycemia was enough to restore beta-cell mass previously
reduced by STZ injection. This effect seemed to be due to hyperglycemia rather
than hyperinsulinemia alone. The data stress the dissociation between beta-cell
regeneration and improvement in islet function in diabetic rats. Our model seems
suitable for studying factors that can improve the plasticity and function of the
pancreas in NIDDM.
PMID- 9648828
TI - Glucose augmentation of mastoparan-stimulated insulin secretion in rat and human
pancreatic islets.
AB - Mastoparan, a tetradecapeptide component of wasp venom, activates heterotrimeric
G-proteins and stimulates exocytosis in several cell types, including the
pancreatic beta-cell. In this study, its effects on insulin secretion were
assessed in both rat and human pancreatic islets, along with the ability of
glucose and alpha-ketoisocaproate (alpha-KIC) to augment mastoparan-stimulated
release. In Ca2+-free Krebs-Ringer bicarbonate buffer containing 2.8 mmol/l
glucose, 20 micromol/l mastoparan stimulated insulin secretion 12- and 14-fold in
rat and human islets, respectively. The inactive analog mastoparan-17 had no
effect on release. Under the same Ca2+-free conditions, 11.1 mmol/l glucose had
no effect on insulin release alone, but augmented mastoparan-stimulated release
by 74% in both rat and human islets. Stimulation of release by mastoparan and
augmentation of release by glucose were unaffected by treatment with pertussis
toxin. The effect of cellular GTP depletion on the mastoparan stimulation of
release and augmentation by alpha-KIC was studied by culturing rat islets in the
presence of 25 microg/ml mycophenolic acid for 20 h. In the control islets, alpha
KIC augmented mastoparan-stimulated insulin release by 80%. In the GTP-depleted
rat islets, mastoparan-stimulated insulin release was not changed, while the
augmentation by alpha-KIC was eliminated. Mannoheptulose completely blocked the
augmentation by glucose. In conclusion, mastoparan stimulates insulin release by
activation of a signal transduction pathway that can be augmented by nutrients
such as glucose and alpha-KIC. Nutrient augmentation of this pathway is heavily
dependent on GTP.
PMID- 9648830
TI - A role for Ca2+-sensitive nonselective cation channels in regulating the membrane
potential of pancreatic beta-cells.
AB - The incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase
activating polypeptide, are proposed to activate a maitotoxin (MTX)-sensitive,
Ca2+-dependent nonselective cation current in pancreatic beta-cells and
insulinoma cells. This MTX-sensitive current is present in human beta-cells as
well as in mouse and rat beta-cells, and is accompanied by a rise in cytosolic
Ca2+ in voltage-clamped cells in which the activation of voltage-dependent Ca2+
channels is prevented. Activation of the nonselective cation current is inhibited
by reduction of disulfide bonds with intracellular, but not extracellular,
dithiothreitol, and is also abolished by intracellular dialysis with trypsin. The
nonselective cation channels that carry this current have a conductance of about
30 pS, with Na+ as the major extracellular cation. We estimate that these cation
channels are expressed on beta-cells at a density similar to that of ATP
sensitive potassium channels (K(ATP) channels) and exhibit spontaneous activity
at basal glucose concentrations. We propose that this spontaneous cation channel
activity constitutes at least part of the depolarizing background conductance
that permits changes in the activity of K(ATP) channels to regulate the resting
potential of beta-cells.
PMID- 9648831
TI - A specific increased expression of insulin receptor substrate 2 in pancreatic
beta-cell lines is involved in mediating serum-stimulated beta-cell growth.
AB - Certain nutrients and growth factors can stimulate pancreatic beta-cell growth.
However, the appropriate mitogenic signaling pathways in beta-cells have been
relatively undefined. In this study, differential gene expression in NEDH rat
insulinoma was compared with NEDH rat primary islet beta-cells. Differential mRNA
display analysis revealed an elevated expression in insulinoma of VL30
transposons, S24 ribosomal protein, and cytochrome-C oxidaseVIIc that is typical
for cells undergoing mitosis. A gene candidate approach revealed that mRNA levels
of the oncogenes c-fos and c-jun were equivalently expressed in insulinoma and
islet cells, as was the mRNA for the mitogenic signal transduction molecule
insulin receptor substrate (IRS)-1. However, in contrast to that of IRS-1, IRS-2
gene expression was 60- to 70-fold higher in the insulinoma tissue compared with
islets, which was reflected at the protein as well as the mRNA level. The
specific elevated IRS-2 expression was a consistent observation across all rodent
pancreatic beta-cell lines. To investigate whether IRS-2 was functional, serum
stimulated beta-cell proliferation was examined in isolated insulinoma cells.
After a 48-h period of serum withdrawal, 24 h of serum refeeding rendered an 8-
to 10-fold increase in [3H]thymidine incorporation into insulinoma cells. This
serum-stimulated DNA synthesis was prevented by inhibitors of tyrosine protein
kinase and phosphatidylinositol (PI) 3-kinase activities, as well as the
activation of mitogen-activated protein (MAP) kinase and p70S6K. Examination of
IRS-mediated signal transduction pathways indicated that after 10-15 min of serum
refeeding, there was increased tyrosine phosphorylation of IRS-2 and pp60, and PI
3-kinase recruitment to IRS-2. Serum also increased the association of growth
factor-bound protein 2/murine sons of sevenless 1 protein to a PI 3-kinase/IRS-2
protein complex. Moreover, serum also activated MAP-kinase (erk-1 and erk-2
isoforms) and 70 kD S6 kinase. Thus IRS-mediated signal transduction pathways are
functional in pancreatic beta-cells. It is conceivable that IRS-2 expression in
beta-cells contributes to maintaining the islet beta-cell population,
complementary to observations in the IRS-2 knockout mouse in which beta-cell mass
is markedly reduced.
PMID- 9648832
TI - Long-term exposure of beta-INS cells to high glucose concentrations increases
anaplerosis, lipogenesis, and lipogenic gene expression.
AB - Chronic exposure of pancreatic beta-cells to high glucose has pleiotropic action
on beta-cell function. In particular, it induces key glycolytic genes, promotes
glycogen deposition, and causes beta-cell proliferation and altered insulin
secretion characterized by sensitization to low glucose. Postglycolytic events,
in particular, anaplerosis and lipid signaling, are thought to be implicated in
beta-cell activation by glucose. To understand the biochemical nature of the beta
cell adaptive process to hyperglycemia, we studied the regulation by glucose of
lipogenic genes in the beta-cell line INS-1. A 3-day exposure of cells to
elevated glucose (5-25 mmol/l) increased the enzymatic activities of fatty acid
synthase 3-fold, acetyl-CoA carboxylase 30-fold, and malic enzyme 1.3-fold.
Pyruvate carboxylase and citrate lyase expression remained constant. Similar
observations were made at the protein and mRNA levels except for malic enzyme
mRNA, which did not vary. Metabolic gene expression changes were associated with
chronically elevated levels of citrate, malate, malonyl-CoA, and conversion of
glucose carbon into lipids, even in cells that were subsequently exposed to low
glucose. Similarly, fatty acid oxidation was suppressed and phospholipid and
triglyceride synthesis was enhanced independently of the external glucose
concentration in cells preexposed to high glucose. The results suggest that a
coordinated induction of glycolytic and lipogenic genes in conjunction with
glycogen and triglyceride deposition, as well as increased anaplerosis and
altered lipid partitioning, contribute to the adaptive process to hyperglycemia
and glucose sensitization of the beta-cell.
PMID- 9648833
TI - Elevated PC-1 content in cultured skin fibroblasts correlates with decreased in
vivo and in vitro insulin action in nondiabetic subjects: evidence that PC-1 may
be an intrinsic factor in impaired insulin receptor signaling.
AB - Membrane glycoprotein PC-1 inhibits insulin receptor (IR) tyrosine kinase
activity and subsequent cellular signaling. PC-1 content is elevated in muscle
and adipose tissue from insulin-resistant subjects, and its elevation correlates
with in vivo insulin resistance. To determine whether elevated PC-1 content is a
primary cause of insulin resistance, we have now measured PC-1 content in
cultured skin fibroblasts from nonobese nondiabetic insulin-resistant subjects
and found that 1) PC-1 content was significantly higher in these cells when
compared with cells from insulin-sensitive subjects (6.7 +/- 0.9 vs. 3.1 +/- 0.6
ng/0.1 mg protein, mean +/- SE, P < 0.01); 2) PC-1 content in fibroblasts was
highly correlated with PC-1 content in muscle tissue (r = 0.95, P = 0.01); 3) PC
1 content in fibroblasts negatively correlated with both decreased in vivo
insulin sensitivity and decreased in vitro IR autophosphorylation; and 4) in
cells from insulin-resistant subjects, insulin stimulation of glycogen synthetase
was decreased. These studies indicate, therefore, that the elevation of PC-1
content may be a primary factor in the cause of insulin resistance.
PMID- 9648834
TI - Renal lactate metabolism and gluconeogenesis during insulin-induced hypoglycemia.
AB - The contribution of gluconeogenic precursors to renal glucose production (RGP)
during insulin-induced hypoglycemia was assessed in conscious dogs. Ten days
after surgical placement of sampling catheters in the right and left renal veins
and femoral artery and an infusion catheter in the left renal artery, systemic
and renal glucose and glycerol kinetics were measured with peripheral infusions
of [6-3H]glucose and [2-13C]glycerol. Renal blood flow was determined with a
flowprobe, and the renal balance of lactate, alanine, and glycerol was calculated
by arteriovenous difference. After baseline, six dogs received 2-h simultaneous
infusions of peripheral insulin (4 mU x kg(-1) x min(-1)) and left intrarenal
[6,6-2H]dextrose (14 micromol x kg(-1) x min(-1)) to achieve and maintain left
renal normoglycemia during systemic hypoglycemia. Arterial glucose decreased from
5.3 +/- 0.1 to 2.2 +/- 0.1 mmol/l; insulin increased from 46 +/- 5 to 1,050 +/-
50 pmol/l; epinephrine, from 130 +/- 8 to 1,825 +/- 50 pg/ml; norepinephrine,
from 129 +/- 6 to 387 +/- 15 pg/ml; and glucagon, from 52 +/- 2 to 156 +/- 12
pg/ml (all P < 0.01). RGP increased from 1.7 +/- 0.4 to 3.0 +/- 0.5 (left) and
from 0.6 +/- 0.2 to 3.2 +/- 0.2 (right) micromol x kg(-1) x min(-1) (P < 0.01).
Whole-body glycerol appearance increased from 6.0 +/- 0.5 to 7.7 +/- 0.7 micromol
x kg(-1) x min(-1)(P < 0.01); renal conversion of glycerol to glucose increased
from 0.13 +/- 0.04 to 0.30 +/- 0.10 (left) and from 0.11 +/- 0.03 to 0.25 +/-
0.05 (right) micromol x kg(-1) x min(-1), (P < 0.05). Net renal gluconeogenic
precursor uptake increased from 1.5 +/- 0.4 to 5.0 +/- 0.4 (left) and from 0.9 +/
0.2 to 3.8 +/- 0.4 (right) micromol x kg(-1) x min(-1) (P < 0.01). Renal lactate
uptake could account for approximately 40% of postabsorptive RGP and for 60% of
RGP during hypoglycemia. These results indicate that gluconeogenic precursor
extraction by the kidney, particularly lactate, is stimulated by
counterregulatory hormones and accounts for a significant fraction of the
enhanced gluconeogenesis induced by hypoglycemia.
PMID- 9648835
TI - Regulation of skeletal muscle hexokinase II by insulin in nondiabetic and NIDDM
subjects.
AB - Impaired muscle glucose phosphorylation to glucose-6-phosphate by hexokinases
(HKs)-I and -II may contribute to insulin resistance in NIDDM and obesity. HK-II
expression is regulated by insulin. We tested the hypothesis that basal and
insulin-stimulated expression of HK-II is decreased in NIDDM and obese subjects.
Skeletal muscle HK-I and HK-II activities were measured in seven lean and six
obese normal subjects and eight patients with NIDDM before and at 3 and 5 h of a
hyperinsulinemic (80 mU x m(-2) x min(-1)) euglycemic clamp. To assess whether
changes in HK-II expression seen during a glucose clamp are likely to be
physiologically relevant, we also measured HK-I and HK-II activity in 10 lean
normal subjects before and after a high-carbohydrate meal. After an overnight
fast, total HK, HK-I, and HK-II activities were similar in lean and obese control
subjects; but HK-II was lower in NIDDM patients than in lean subjects (1.42 +/-
0.16 [SE] vs. 2.33 +/- 0.24 nmol x min(-1) x mg(-1) molecular weight, P < 0.05)
and accounted for a lower proportion of total HK (33 +/- 3 vs. 47 +/- 3%, P <
0.025). HK-II (but not HK-I) activity increased during the clamp in lean and
obese subjects by 34 and 36% after 3 h and by 14 and 22% after 5 h of
hyperinsulinemia; no increase was found in the NIDDM patients. In the lean
subjects, muscle HK-II activity also increased by 15% 4 h after the meal, from
2.47 +/- 0.19 basally to 2.86 +/- 0.28 nmol x min(-1) x mg(-1) protein (P <
0.05). During the clamps, muscle HK-II activity correlated with muscle citrate
synthase activity in the normal subjects (r = 0.58, P < 0.05) but not in the
NIDDM patients. A weak relationship was noted between muscle HK-II activity and
glucose disposal rate at the end of the clamp when all three groups were combined
(r = 0.49, P < 0.05). In summary, NIDDM patients have lower muscle HK-II activity
basally and do not increase the activity of this enzyme in response to a 5-h
insulin stimulus. This defect may contribute to their insulin resistance. In
nondiabetic obese subjects, muscle HK-II expression and its regulation by insulin
are normal.
PMID- 9648836
TI - Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation,
and oxidant-induced apoptosis.
AB - Aminoguanidine (AG) treatment, like nerve growth factor (NGF) treatment, prevents
diabetes-induced apoptosis of retinal Muller cells in the rat eye, but the
mechanism involved is unknown. In this study, the effects of preincubation with
AG on oxidant-induced apoptosis, oxidant-induced intracellular reactive oxygen
species (ROS) production, and lipid peroxidation were determined in rat retinal
Muller cells and compared with the effects of NGF, a protein that protects
neuronal cells from oxidative stress. The effect of AG on rabbit vitreous lipid
peroxide levels was also determined. After exposure to increasing concentrations
of H2O2, there was a corresponding increase in the percentage of apoptotic Muller
cells. Preincubation with AG for 48 h completely inhibited oxidant-induced
apoptosis in response to 10 micromol/l H2O2 (+AG 0 vs. 10 micromol/l, NS), and
reduced the percentage of apoptotic cells in response to 50 micromol/l H2O2 by
50% (+AG vs. -AG, P < 0.01). Longer preincubation did not increase the
antiapoptotic effect of AG. The effect of AG was dose-dependent. Similar results
were obtained after preincubation with NGF. Both AG and NGF preincubation
prevented the twofold increase in oxidant-induced lipid peroxides. The fivefold
increase in oxidant-induced ROS production was decreased 100% by NGF, but only
61% by AG preincubation. The twofold increase in vitreous lipid peroxide level in
diabetic rabbits was completely prevented by AG treatment. AG reduced H2O2
induced benzoate hydroxylation in a dose-dependent manner. Intracellular
glutathione content was unchanged. These data demonstrate that AG can act as an
antioxidant in vivo, quenching hydroxyl radicals and lipid peroxidation in cells
and tissues and preventing oxidant-induced apoptosis.
PMID- 9648837
TI - Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM
patients.
AB - It has been suggested that hereditary risk for hypertension and cardiovascular
disease (CVD) as well as intrauterine growth may be involved in the pathogenesis
of diabetic nephropathy. In the present study, we investigated the influence of
familial and perinatal risk factors on the occurrence of micro- and
macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with >
or =5 years' duration of IDDM was screened for microalbuminuria. Data on family
history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth
weight, gestational age, and duration of breastfeeding; and maternal education,
smoking, hypertension, and proteinuria during pregnancy were collected. We
identified 75 patients with an albumin excretion rate > or =15 microg/min in more
than two overnight urinary samples and compared them in a nested case-control
study with three normoalbuminuric control subjects per patient from the same
cohort, matched for diabetes duration. Perinatal factors were analyzed in all
patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225
control subjects. In univariate analysis, hypertension in parents (odds ratio
[OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during
pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were
significantly associated with the development of micro- and macroalbuminuria.
When adjusted for other familial and perinatal factors, current mean blood
pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration,
using logistic regression analyses, only parental hypertension in all patients
and maternal smoking during pregnancy and low level of maternal education in full
term patients were independent risk factors. When patients with poor glycemic
control were analyzed separately, familial CVD, poor metabolic control, parental
hypertension, maternal smoking during pregnancy, and level of maternal education
were independent risk factors, with the adjusted OR markedly increased, compared
with the matched subgroup with better HbA1c. In conclusion, familial hypertension
and CVD, maternal smoking during pregnancy, and low level of maternal education
may independently increase the risk for incipient nephropathy in full-term
offspring who later develop IDDM. Current poor glycemic control seemed to
increase the effect of these risk factors.
PMID- 9648838
TI - Contribution of the endothelium to transcapillary insulin transport in rat
isolated perfused hearts.
AB - Capillary endothelial cells are thought to limit the transport of insulin from
the vascular to the interstitial space, resulting in attenuated hormonal action
at target sites. This study examined the contribution of endothelial cells to the
regulation of transcapillary insulin transport in rat hearts in vitro. Hearts
were perfused with a protein-free buffer that resulted in the generation of a
substantial amount of interstitial fluid (transudate) that was collected at the
surface of ventricles. Insulin (0.05-1 U/l) was added to the perfusate, and its
transfer kinetics to and clearance from the interstitium were analyzed from
insulin measurements in transudate of hearts with intact or collagenase-disrupted
endothelium. In endothelium-intact hearts (n = 5-8), the steady-state insulin
concentration in transudate was 29 +/- 4, 30 +/- 2, 53 +/- 1, 103 +/- 6, and 97
+/- 4% of perfusate concentrations at 0.05, 0.1, 0.2, 0.5, and 1 U/l insulin,
respectively. The corresponding apparent rate constants for transport (k(in))
increased from 0.03/min to -0.27/min, indicating a nonsaturable transport
process. The transport rate for [3H]insulin (1.2 nmol/l; n = 5) was identical to
an equimolar concentration of insulin (0.2 U/l), strongly indicating the same
mode of transport. In endothelium-disrupted hearts (n = 3-5), the same
perfusate/transudate concentration ratios were observed--that is, a gradient at
low insulin concentrations (0.05-0.2 U/l) and complete equilibration at higher
insulin concentrations, suggesting a contribution of reabsorption processes back
into the vascular space in the generation of the gradient. Finally, inhibition of
endothelial nitric oxide (NO) formation by NG-nitro-L-arginine (200 micromol/l)
affected neither k(in) nor the extent of transendothelial insulin transport in
the presence of an intact endothelium. We concluded that 1) capillary endothelial
cells affect the transcapillary transport of insulin by slowing the transfer to
the interstitium, 2) insulin is transported by a bidirectional convective
transport rather than by a saturable receptor-mediated mechanism, and 3)
endothelium-derived NO is without effect on transcapillary insulin transport in
this model.
PMID- 9648839
TI - Cyclic nucleotide phosphodiesterase 3 expression in vivo: evidence for tissue
specific expression of phosphodiesterase 3A or 3B mRNA and activity in the aorta
and adipose tissue of atherosclerosis-prone insulin-resistant rats.
AB - With a view of understanding the potential roles of phosphodiesterase (PDE)3 in
the acceleration of atherosclerosis in diabetes, we have analyzed the in vivo
levels of low Km cAMP PDE3 and PDE4 activities as well as PDE3A and PDE3B mRNA in
a relevant animal model. The JCR:LA-cp rat is a unique strain that develops
obesity, insulin resistance, and vasculopathy when homozygous for the autosomal
recessive cp gene (cp/cp). Lean rats, bred (designated +/?) as a 2:1 mixture of
animals that are heterozygous (cp/+) or homozygous normal (+/+), are
metabolically normal. We find that PDE3 activity is the major low Km cAMP
activity in the aorta of cp/cp rats and is approximately twofold higher than that
in lean +/? rats. PDE3A mRNA levels in middle-aged cp/cp rats are also elevated,
approximately threefold, compared with those of +/? rats or young 12-week-old
cp/cp rats. Thus, in the aorta of atherosclerosis-prone insulin-resistant cp/cp
rats, PDE3A gene expression is upregulated, resulting in significantly higher
PDE3 activity. This upregulation of PDE3A mRNA levels was a rather unique
phenomenon to the aorta of JCR:LA-cp rats compared with that in the aorta of
other rat strains. This result is consistent with our hypothesis that an
increased PDE3 activity in aortic smooth muscle cells may contribute to
accelerated atherosclerosis in diabetes. Furthermore, determination of PDE3
activity and PDE3A and PDE3B mRNA levels in heart and white and brown fat tissues
of JCR:LA-cp rats revealed that PDE3B mRNA and activity in white adipose tissue
is downregulated in this diabetic animal model, and that PDE3A and PDE3B genes
are tissue-specifically expressed and differentially regulated in aorta and
adipose tissue, respectively, under hyperinsulinemic conditions.
PMID- 9648840
TI - Functional analyses of novel mutations in the sulfonylurea receptor 1 associated
with persistent hyperinsulinemic hypoglycemia of infancy.
AB - The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the
sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit,
Kir6.2, regulates insulin secretion in the pancreas. Mutations in both the Kir6.2
and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of
infancy (PHHI), a disorder of pancreatic beta-cell function characterized by
excess insulin secretion and hypoglycemia. We have studied the functional
properties of novel SUR1 mutations identified in PHHI patients, including H125Q,
N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. R1394H and deltaF1388 SUR1, a
previously identified PHHI mutation, resulted in no functional channels when
coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q,
and G1382S SUR1 generated functional channels in the absence of ATP. With the
exception of N188S and H125Q, all mutants had reduced response to stimulation by
MgADP. These results indicate that lack of, or reduction of, K(ATP) channel
sensitivity to MgADP is a common molecular defect associated with the disease.
The mutant channels also showed varied response to activation by the potassium
channel opener diazoxide. Because these mutations are distributed throughout the
molecule, our data have new implications for structure-function relationships of
the K(ATP) channel, suggesting that structural elements in SUR1 outside of the
two nucleotide-binding folds are also important in regulating channel activity.
PMID- 9648841
TI - Mutations in hepatocyte nuclear factor 1beta are not a common cause of maturity
onset diabetes of the young in the U.K.
PMID- 9648842
TI - Identification of polymorphisms in the receptor for advanced glycation end
products (RAGE) gene: prevalence in type 2 diabetes and ethnic groups.
PMID- 9648843
TI - CTLA4 gene haplotypes cannot protect from IDDM in the presence of high-risk HLA
DQ8 or DQ2 alleles in German families.
PMID- 9648844
TI - Diabetic patients produce an increase in coronary sinus endothelin 1 after
coronary artery bypass grafting.
AB - Diabetes is associated with altered vascular responses, and diabetic patients
demonstrate increased morbidity and mortality after coronary artery bypass
grafting (CABG). We tested whether endothelin (ET)-1 levels in this patient
population differed from those in nondiabetic subjects after CABG. Of 14
consecutive patients who underwent CABG by the same surgeon, 7 had type 2
diabetes and 7 were nondiabetic. The two groups did not differ significantly in
preoperative ejection fraction, number of vessels bypassed, cross-clamp time, or
Parsonnet's score. Coronary sinus blood samples were obtained before cardioplegic
arrest and then obtained at 1 and 15 min after each of two reperfusion periods:
reperfusion A (native coronary perfusion plus the left internal mammary artery),
reperfusion B (saphenous vein graft perfusion). ET-1 was significantly increased
at all reperfusion time points in diabetic patients compared with nondiabetic
patients. In diabetic patients, reperfusion after CABG can trigger the release of
ET-1, which may be a contributing factor in the increased cardiac morbidity seen
in this patient population.
PMID- 9648845
TI - Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q:
results of novel discordant sib-pair analysis.
AB - Diabetic nephropathy (DN) clusters in families with type 1 diabetes and the
degree of clustering suggests that a major gene having a common disease allele
may be responsible. To investigate the chromosomal regions containing genes for
the renin-angiotensin system, we performed a linkage study using pairs of
siblings with type 1 diabetes who were discordant for DN. Theoretical
considerations supported by simulation studies indicated that such discordant
pairs, rather than the usual concordant pairs, would be more effective in
detecting a major susceptibility gene for DN. We applied this novel strategy to
test for linkage between DN and chromosomal regions containing genes for the ACE,
angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1). Two polymorphic
markers were genotyped in the vicinity of each of the three loci in 66 discordant
sib pairs and were analyzed with multipoint methods. The regions containing ACE
and AGT loci were not linked with DN, while the region containing the AT1 locus
showed linkage with DN. As a result of these positive findings, eight additional
polymorphic markers spanning a 63-cM region around AT1 locus were genotyped.
Linkage was demonstrated between DN and a 20-cM region that includes AT1 (P = 7.7
x 10(-5)), an obvious candidate gene for DN. To investigate whether AT1 could
account for the observed linkage, we sequenced all exons, splicing junctions, and
the promoter region and examined the identified polymorphisms/mutations for
association with DN using the transmission disequilibrium test. Four new
polymorphisms in the gene were found, but neither these nor previously described
polymorphisms were associated with DN. Thus, while our study does not implicate
AT1 itself in the etiology of DN, it provides very strong evidence that a 20-cM
region around AT1 contains a major locus for susceptibility to DN.
PMID- 9648846
TI - Homeobox genes in the developing mouse brain.
AB - Any list of past and recent findings on vertebrate brain prenatal development
would have to include the fundamental roles of homeobox genes, the genes encoding
the nuclear regulatory homeodomain proteins. The discovery of homeobox genes and
their involvement as master regulatory elements in programming the development of
an embryo into a complete adult organism has provided a key to our understanding
of ontogenesis. Also, the correlation of mouse developmental mutants and their
corresponding human syndromes with mutations in homeobox genes has provided
further evidence for the fundamental role of homeobox genes during the vertebrate
brain embryonic development. Here, we review the expression patterns and the
phenotypes of gene mutations that implicate a large repertoire of mouse homeobox
genes in the specification of neuronal functions during brain embryogenesis.
PMID- 9648847
TI - Cloning of zebrafish neurofilament cDNAs for plasticin and gefiltin: increased
mRNA expression in ganglion cells after optic nerve injury.
AB - During retinal growth and optic axon regeneration, the differential expression of
the neuronal intermediate filament proteins, plasticin and gefiltin, in the
goldfish visual pathway suggests that these proteins support programmed axonal
growth. To investigate plasticin and gefiltin during axonogenesis, we turned to
the zebrafish, a system that is more amenable to mutational analysis. As a first
step, we demonstrated that the intermediate filament compositions of goldfish and
zebrafish are similar. In addition, the cDNAs for zebrafish plasticin and
gefiltin were cloned and characterized. Using in situ hybridization in retina, we
show increased mRNA levels for these proteins following optic nerve crush.
Zebrafish plasticin and gefiltin peak and return to baseline levels of expression
more rapidly than in goldfish. Furthermore, in the unoperated eye of experimental
fish, there was a moderate increase in the levels of plasticin and gefiltin mRNA,
suggesting that soluble factors influence the expression of these proteins. The
successive expression of plasticin and gefiltin suggests that these neuronal
intermediate filament proteins are integral components of axonogenesis. The
cloning and characterization of cDNAs for plasticin and gefiltin permit
mutational analyses of these proteins during zebrafish axonogenesis.
PMID- 9648848
TI - Retrovirus-mediated double transduction of the GTPCH and PTPS genes allows 6
pyruvoyltetrahydropterin synthase-deficient human fibroblasts to synthesize and
release tetrahydrobiopterin.
AB - The tetrahydrobiopterin (BH4) cofactor is essential for the aromatic amino acid
hydroxylases that are involved in phenylalanine degradation and catecholamine and
serotonin biosynthesis. Furthermore, BH4 is an essential and limiting cofactor
for all types of nitric oxide synthases. BH4 deficiency results in
hyperphenylalaninemia and monoamine neurotransmitter depletion associated with
progressive mental retardation and is most commonly due to autosomal recessive
mutations in 6-pyruvoyltetrahydropterin synthase (PTPS), the second enzyme for
cofactor biosynthesis. Due to the relatively poor blood-brain barrier penetration
of the cofactor, conventional therapy requires, besides oral doses of synthetic
BH4, administration of neurotransmitter precursors and an aromatic amino acid
decarboxylase inhibitor. The outcome of this therapy is not always beneficial. In
this study we transduced into primary patient fibroblasts the human cDNAs for the
BH4 biosynthetic enzymes GTP cyclohydrolase I and PTPS, expressed from different
retroviral vectors. This allowed BH4 biosynthesis in originally PTPS-deficient
cells. Moreover, the double-transduced fibroblasts released between 200 and 800
pmol of BH4/10(6) cells/day. Such engineered fibroblasts may be grafted into the
central nervous system and used as depository cells for constitutive delivery of
BH4.
PMID- 9648849
TI - The cell-specific silencer region of the human dopamine beta-hydroxylase gene
contains several negative regulatory elements.
AB - Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to
noradrenaline and is selectively expressed in noradrenergic and adrenergic
neurons in the nervous system. Transient transfection assays have indicated that
cell-specific transcription of the human DBH gene may require a cell-specific
silencer region residing at -486 to -263 bp upstream of the transcription start
site. This region includes a putative DBH negative regulatory element (DNRE) with
sequence homology to the restrictive element-1 (RE1)/neuron-restrictive silencer
element identified in many other neural-specific genes. However, DNRE exerted
negative regulation in both neuronal and nonneuronal cells alike, and site
directed mutation of this element did not significantly diminish the repressive
activity of the DBH silencer region. Furthermore, expression of RE1-silencing
transcription factor/neuron-restrictive silencer factor repressed neither DBH nor
tyrosine hydroxylase promoter activity. We now report identification of three
protein binding sites in the silencer region of the human DBH gene: SI at -271 to
-250 bp, SII at -316 to -295 bp, and SIII at -348 to -324 bp. In vitro binding
studies showed that SI and SIII, but not SII, interact with nuclear proteins from
DBH-negative cells in a cell-specific manner. Furthermore, SI and SIII
preferentially repressed the heterologous thymidine kinase and homologous DBH
proximal promoter activities in nonneuronal cells. Taken together, the cell
specific silencer function of the upstream DBH region appears to involve several
cis-regulatory elements, including two cell-specific repressor elements, SI and
SIII, and a general negative regulatory element, DNRE. Based on these data, we
propose that a highly restricted pattern of DBH gene expression in
(nor)adrenergic cells of the nervous system may be controlled by multiple
negative regulatory elements/silencers.
PMID- 9648850
TI - Differentiation of a catecholaminergic CNS cell line modifies tyrosine
hydroxylase transcriptional regulation.
AB - Recently, a tyrosine hydroxylase (TH)-expressing CNS-derived cell line, CAD, was
obtained that is capable of undergoing reversible morphological differentiation.
The isolation of the CAD line allowed us to ask whether different DNA regulatory
elements direct TH transcription when cells are growing and undifferentiated
versus postmitotic and differentiated. To this end, we compared expression of a
transiently transfected bacterial chloramphenicol acetyltransferase reporter gene
under the transcriptional control of TH 5' flanking DNA in CAD cells grown in the
presence and absence of serum. Mutational analysis indicates that CAD cells
differently regulate TH transcription depending on their state of
differentiation. In both states, the cyclic AMP response element and AP1 site
each activate transcription. However, in undifferentiated cells, the dyad/E-box
element represses expression by approximately 2.7-fold, whereas it modestly
activates transcription in differentiated cells. The role of the dyad/ E-box as a
repressor correlates well with the two- to threefold lower amount of endogenous
TH protein present in the undifferentiated CAD cells. This study demonstrates the
differential use of TH DNA regulatory elements in proliferating, undifferentiated
and nonproliferating, differentiated immortalized neuronal cells.
PMID- 9648851
TI - Regional expression and regulation of alternative forms of mRNAs derived from two
distinct transcription initiation sites of the rat mGluR5 gene.
AB - Metabotropic glutamate receptor (mGluR) subtype 5 is expressed in both neuronal
and glial cells and is thought to play an important role in neuronal plasticity.
This expression is up-regulated during the early postnatal period and is induced
in cultured astrocytes by specific growth factors. To investigate the mechanism
underlying the regulation of mGluR5 expression, we isolated and characterized
genomic clones containing the 5'-upstream exons and their flanking regions of the
mGluR5 gene. On the basis of the mGluR5 genomic structure, cDNA recloning of the
5'-extreme region of mGluR5 as well as primer extension analysis indicated that
mGluR5 mRNA is generated from two alternative first exons, termed exon 1A and
exon 1B, which are separated by 1,949 bp and then connected to the common exon 2.
Northern blot and in situ hybridization analyses indicated that two distinct
transcription initiation sites are commonly used in the expression of mGluR5 mRNA
in various, but specialized, brain regions and that these two alternative forms
of mGluR5 mRNA are similarly up-regulated or down-regulated during the early
postnatal period, depending on the brain regions. The two mRNAs are also
expressed in cultured astrocytes but respond differently to growth factor
mediated induction. This study provides the genetic basis indicating the diverse
mechanisms involved in the regulation of mGluR5 expression.
PMID- 9648852
TI - Activation of endogenous antioxidant defenses in neuronal cells prevents free
radical-mediated damage.
AB - Dopamine (DA) is oxidized to the neurotoxic prooxidant species H2O2, OH., and DA
quinones. We tested whether dimethyl fumarate (DMF), an electrophile shown to
induce a pleiotropic antioxidant response in nonneuronal cells, could reduce the
toxicity of DA metabolites in neural cells. Treatment of the N18-RE-105
neuroblastoma-retina hybridoma cell line with 30-150 microM dopamine led to cell
death within 24 h, which increased steeply with dose, decreased with higher
plating density, and was blocked by the H2O2-metabolizing enzyme catalase.
Pretreatment with DMF (30 microM, 24 h) significantly attenuated DA and H2O2
toxicity (40-60%) but not that caused by the calcium ionophore ionomycin. DMF
treatment also elevated total intracellular GSH and increased activities of the
antioxidant enzymes quinone reductase (QR), glutathione S-transferase (GST),
glutathione reductase, and the pentose phosphate enzyme glucose-6-phosphate
dehydrogenase. To assess the protective efficacy of QR and GST, a stable cell
line was constructed in which these enzymes were overexpressed. Cell death in the
overexpressing line was not significantly different from that in a cell line
expressing normal QR and GST activities, indicating that these two enzymes alone
are insufficient for protection against DA toxicity. Although the relative
importance of a single antioxidant enzyme such as QR or GST may be small,
antioxidant inducers such as DMF may prove valuable as agents that elicit a broad
spectrum neuroprotective response.
PMID- 9648853
TI - Cytokine-induced accumulation of very long-chain fatty acids in rat C6 glial
cells: implication for X-adrenoleukodystrophy.
AB - X-Adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of very long
chain fatty acids (VLCFA) with subsequent manifestation of neuroinflammatory
disease. To investigate the possible role of proinflammatory cytokines in the X
ALD disease process, we examined the effect of cytokines on the metabolism of
VLCFA in C6 glial cells expressing oligodendrocyte-like properties. C6 glial
cells under serum-free conditions were treated with different combinations of
cytokines (tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma) or
cytokine with bacterial lipopolysaccharide (LPS). Cytokine-treated C6 cells had
higher concentrations of VLCFA, measured as percent weight and also as
C26:0/C22:0 ratio, which were 300-400% as compared with the controls. We also
found increased levels of C26:1 in cytokine-treated cells. The accumulation of
VLCFA paralleled the decrease (35-55%) in peroxisomal beta-oxidation activity and
a 12- to 14-fold increase in the production of nitric oxide (NO). Individual
cytokines were unable either to produce NO or to increase the levels of VLCFA in
C6 cells. Inhibition of cytokine-induced NO production by L-N-methylarginine, an
inhibitor of NO synthase (NOS), and N-acetylcysteine, an inhibitor of cytokine
mediated induction of inducible NOS, normalized the peroxisomal beta-oxidation
activity and the levels of VLCFA, suggesting a role for the proinflammatory
cytokines and NO toxicity in the neuropathological changes associated with
abnormal VLCFA metabolism (e.g., X-ALD). X-ALD is a peroxisomal disease having
deficient oxidation of VLCFA, resulting in the excessive accumulation of VLCFA in
all tissues but especially in brain. We observed greater increase in levels of
VLCFA in the inflammatory region of ALD brain (in the demyelinating plaque and
the area around the plaque) than in the normal-looking area away from the plaque;
this also indicates that cytokines in the proinflammatory region may augment the
VLCFA defect caused by the inherited abnormality in X-ALD brain. Although C6
glial cultured cells do not reflect the X-ALD model precisely, the observed
relationship between the cytokine-induced inhibition of the oxidation of VLCFA,
excessive accumulation of VLCFA, and excessive production of NO and their
normalization by inhibitors of NOS in C6 glial cells suggests that NO-mediated
toxicity may play a role in VLCFA-associated neuroinflammatory diseases (e.g., X
ALD).
PMID- 9648854
TI - Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in
neuronal PC12 cells after stimulation with tumor necrosis factor
alpha/lipopolysaccharide.
AB - Exposure of neuronal PC12 cells, differentiated by nerve growth factor, to tumor
necrosis factor-alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS) resulted
in de novo synthesis of inducible nitric oxide synthase (iNOS) mRNA and protein
with an increase up to 24 h. Brain NOS expression was unaffected. The induction
of iNOS in differentiated PC12 cells was associated with cell death characterized
by features of apoptosis. The NOS inhibitors N-monomethylarginine,
aminoguanidine, and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine.HCl prevented
TNF-alpha/LPS-induced cell death and DNA fragmentation, suggesting that the TNF
alpha/LPS-induced cell death is mediated by iNOS-derived NO. This hypothesis is
supported by the finding that addition of L-arginine, which serves as a precursor
and limiting factor of enzyme-derived NO production, potentiated TNF-alpha/LPS
induced loss of viability.
PMID- 9648855
TI - Oxidative stress induces a form of programmed cell death with characteristics of
both apoptosis and necrosis in neuronal cells.
AB - Oxidative stress is implicated in a number of neurological disorders including
stroke, Parkinson's disease, and Alzheimer's disease. To study the effects of
oxidative stress on neuronal cells, we have used an immortalized mouse
hippocampal cell line (HT-22) that is particularly sensitive to glutamate. In
these cells, glutamate competes for cystine uptake, leading to a reduction in
glutathione and, ultimately, cell death. As it has been reported that protein
kinase C activation inhibits glutamate toxicity in these cells and is also
associated with the inhibition of apoptosis in other cell types, we asked if
glutamate toxicity was via apoptosis. Morphologically, glutamate-treated cells
underwent plasma membrane blebbing and cell shrinkage, but no DNA fragmentation
was observed. At the ultrastructural level, there was damage to mitochondria and
other organelles although the nuclei remained intact. Protein and RNA synthesis
inhibitors as well as certain protease inhibitors protected the cells from
glutamate toxicity. Both the macromolecular synthesis inhibitors and the protease
inhibitors had to be added relatively soon after the addition of glutamate,
suggesting that protein synthesis and protease activation are early and distinct
steps in the cell death pathway. Thus, the oxidative stress brought about by
treatment with glutamate initiates a series of events that lead to a form of cell
death distinct from either necrosis or apoptosis.
PMID- 9648856
TI - Association of the Src family tyrosine kinase Fyn with TrkB.
AB - Fyn tyrosine kinase, a member of the Src family, was recently reported to be
present in neurons and glia cells. We investigated whether Fyn is involved in the
Trk-dependent signal transduction pathways of neurotrophin. The Fyn-Src homology
domain 2 (SH2) was observed to associate in vitro with the intracellular domain
of TrkB (ICD-TrkB). This association was dependent on the autophosphorylation of
ICD-TrkB. The Fyn-SH2 domains bound to phosphorylated ICD-TrkB (pICD-TrkB) with
an affinity similar to the binding of phospholipase Cgamma (PLCgamma)-SH2 domains
to its autophosphorylation site in TrkB. The Src-SH2 domains showed substantially
lower affinity with pICD-TrkB, suggesting that the association between Fyn-SH2
and pICD-TrkB is not due to nonspecific interactions of SH2 domains with
phosphorylated tyrosine residues. This is further supported by the observation
that Fyn-SH2 was able to trap phosphorylated TrkB in cell lysate prepared from
primary rat cortical neurons stimulated with brain-derived neurotrophic factor
(BDNF). In contrast, endogenous Fyn was coprecipitated with TrkB from cortical
neurons without BDNF stimulation. This basal association showed a threefold
increase on BDNF stimulation, probably due to the SH2/phosphotyrosine interaction
that was observed in the cell-free system. All these data suggest the involvement
of Fyn in the neurotrophin signal transduction pathways downstream of TrkB.
PMID- 9648857
TI - AMPA receptor-mediated excitotoxicity in human NT2-N neurons results from loss of
intracellular Ca2+ homeostasis following marked elevation of intracellular Na+.
AB - Human NT2-N neurons express Ca2+-permeable alpha-amino-3-hydroxy-5
methylisoxazole-4-propionic acid glutamate receptors (AMPA-GluRs) and become
vulnerable to excitotoxicity when AMPA-GluR desensitization is blocked with
cyclothiazide. Although the initial increase in intracellular Ca2+ levels
([Ca2+]i) was 1.9-fold greater in the presence than in the absence of
cyclothiazide, Ca2+ entry via AMPA-GluRs in an early phase of the exposure was
not necessary to elicit excitotoxicity in these neurons. Rather, subsequent
necrosis was caused by a >40-fold rise in [Na+]i, which induced a delayed [Ca2+]i
rise. Transfer of the neurons to a 5 mM Na+ medium after AMPA-GluR activation
accelerated the delayed [Ca2+]i rise and intensified excitotoxicity. Low-Na+
medium-enhanced excitotoxicity was partially blocked by amiloride or dizocilpine
(MK-801), and completely blocked by removal of extracellular Ca2+, suggesting
that Ca2+ entry by reverse operation of Na+/Ca2+ exchangers and via NMDA
glutamate receptors was responsible for the neuronal death after excessive Na+
loading. Our results serve to emphasize the central role of neuronal Na+ loading
in AMPA-GluR-mediated excitotoxicity in human neurons.
PMID- 9648858
TI - Increase of adenylate kinase isozyme 1 protein during neuronal differentiation in
mouse embryonal carcinoma P19 cells and in rat brain primary cultured cells.
AB - Adenylate kinase (AK), which catalyzes the equilibrium reaction among AMP, ADP,
and ATP, is considered to participate in the homeostasis of energy metabolism in
cells. Among three vertebrate isozymes, AK isozyme 1 (AK1) is present prominently
in the cytosol of skeletal muscle and brain. When mouse embryonal carcinoma P19
cells were differentiated by retinoic acid into neural cells, the amount of AK1
protein and enzyme activity increased about fivefold concomitantly with
neurofilament (NF). Double-immunofluorescence staining showed that both AK1 and
NF were located in neuronal processes as well as the perinuclear regions in
neuron-like cells, but not in glia-like cells. The amount of brain-type creatine
kinase increased only twofold during P19 differentiation. The AK isozyme 2, which
was not detected in adult mouse brain, was found in P19 cells and did not
increase during the differentiation. Mitochondrial AK isozyme 3, which uses GTP
instead of ATP as a phosphate donor, was increased significantly.
Immunohistochemical analysis with the primary cultured cells from rat cerebral
cortex showed similar cellular localization of AK1 to those observed with
differentiated P19 cells. These results suggest an important role of this enzyme
in neuronal functions and in neuronal differentiation.
PMID- 9648859
TI - Nuclear factor of activated T cells (NFAT) as a new component of the signal
transduction pathway in glioma cells.
AB - Cyclosporin A (CsA) exerts its immunosuppressive effect by inhibiting the
activity of nuclear factor of activated T cells (NFAT), thus preventing
transcriptional induction of several cytokine genes. This effect is mediated
through inactivation of the phosphatase calcineurin, which inhibits translocation
of an NFAT component to the nucleus. We have previously reported that CsA
inhibits the growth of rat C6 glioma cells in a dose-dependent manner and induces
apoptotic cell death. Here, we report that NFAT DNA-binding activity is present
in the nuclear extracts from C6 glioma cells and that CsA treatment inhibits the
formation of a functional NFAT complex. We provide evidence for the presence of a
group of NFATc proteins in proliferating glioma cells. Immunoblot analyses show
that stimulation of C6 glioma cells with a calcium-inducing agent, ionomycin,
alters NFATc migration on sodium dodecyl sulfate-polyacrylamide gel
electrophoresis. This alteration is inhibited by simultaneous treatment with CsA,
suggesting a calcineurin involvement in the regulation of glioma NFATc proteins.
Direct immunofluorescence reveals the presence of NFATc proteins in nuclei of
proliferating glioma cells and their disappearance in CsA-treated cells. These
data point to a new mechanism of transcription regulation in glioma cells and
provide an explanation for the observed sensitivity of glioma cells to CsA.
PMID- 9648860
TI - Functional analysis and tissue-specific expression of Drosophila Na+,K+-ATPase
subunits.
AB - We have previously purified and characterized a nervous system-specific
glycoprotein antigen from adult Drosophila heads, designated Nervana [nerve
antigen (NRV)] and identified two separate genes coding for three different
proteins. All three proteins share homology with the beta subunits of Na+,K+
ATPase from various other species. In this study we have isolated a new
Drosophila Na+,K+-ATPase alpha subunit cDNA clone (PSalpha; GenBank accession no.
AF044974) and demonstrate expression of functional Na+,K+-ATPase activity when
PSalpha mRNA is coinjected into Xenopus oocytes along with any of the three
different Nrv mRNAs. Western blotting, RNase protection assays, and
immunocytochemical staining of adult fly sections indicate that NRV2 is expressed
primarily in the nervous system. Staining is most intense in the brain and
thoracic ganglia and is most likely associated with neuronal elements. NRV1 is
more broadly expressed in muscle and excretory tissue and also shows diffuse
distribution in the nervous system. Similar to other species, Drosophila
expresses multiple isoforms of Na+,K+-ATPase subunits in a tissue- and cell type
specific pattern. It will now be possible to use the advantages of Drosophila
molecular and classical genetics to investigate the phenotypic consequences of
altering Na+,K+-ATPase expression in various cell and tissue types.
PMID- 9648861
TI - The calcitonin gene-related peptide-induced acetylcholinesterase synthesis in
cultured chick myotubes is mediated by cyclic AMP.
AB - In vertebrate neuromuscular junctions, post-synaptic specialization includes
aggregation of acetylcholine receptors (AChRs) and acetylcholinesterase (AChE).
The motor nerve provides soluble factors and electrical activity to achieve this
striking localization of AChRs/AChE. Calcitonin gene-related peptide (CGRP), a
neuropeptide synthesized by motor neurons, is able to stimulate the expression of
AChR in cultured myotubes. Similar to AChR regulation, synthesis of AChE in
cultured chick myotubes is also stimulated by CGRP. Application of CGRP onto
cultured myotubes stimulated the accumulation of intracellular cyclic AMP (cAMP)
as well as the expression of AChE mRNA and protein. However, the enzymatic
activity of AChE remained unchanged. In cultured myotubes, various drugs
affecting the intracellular level of cAMP, such as N6,O2'-dibutyryladenosine
3',5'-cyclic monophosphate, cholera toxin, and forskolin, could mimic the effect
of CGRP in stimulating the expression of AChE. When myotubes were transfected
with cDNA encoding constitutively active mutant Galpha(s), the intracellular cAMP
synthesis was increased. The increase in cAMP level was in parallel with an
increase in the expression of AChE, whereas transfection of active mutant
Galpha(i) cDNA decreased the cAMP level as well as the AChE expression. In
addition, expression of collagen-tailed AChE was up-regulated by the cAMP
pathway. These findings indicated that CGRP-induced AChE regulation is mediated
by the cAMP pathway and represented the first evidence to suggest that the
regulation of mRNA synthesis of AChR and AChE can be mediated by the same neuron
derived factor.
PMID- 9648862
TI - Neurotrophic factors prevent ceramide-induced apoptosis downstream of c-Jun N
terminal kinase activation in PC12 cells.
AB - Neurotrophic factors prevent apoptosis of PC12 cells in serum-free medium. The
present study determines whether neurotrophic factors can prevent ceramide
induced apoptosis in PC12 cells and investigates the role that c-Jun N-terminal
kinase (JNK) activation may play in this system. Ceramide-induced apoptosis was
inhibited by nerve growth factor, basic fibroblast growth factor, pituitary
adenylyl cyclase-activating peptide, 4-(8-chlorophenylthio)cyclic AMP, and the
caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp fluoromethyl ketone (zVAD
FMK). It was surprising that inhibition of extracellular signal-regulated kinase
and/or phosphatidylinositol 3-kinase did not markedly block the protective
effects exerted by neurotrophic factors against ceramide-induced apoptosis,
suggesting that neurotrophic factors can promote survival independently of these
signaling pathways. Treatment of PC12 cells with ceramide resulted in a time
dependent increase in JNK activity. However, neither neurotrophic factors nor
zVAD-FMK attenuated ceramide-stimulated JNK activation. Further experiments
indicated that ceramide-induced apoptosis in PC12 cells requires new protein
synthesis, and that nerve growth factor and zVAD-FMK can prevent apoptosis after
JNK activity has been detected. These results indicate that ceramide-induced JNK
activation is an early event and may be required for the expression of essential
components of the apoptotic machinery. It is anticipated that neurotrophic
factors inhibit ceramide-induced apoptosis by affecting signaling events
downstream of JNK activation.
PMID- 9648863
TI - Age-dependent differential regulation of sensory neuropeptides by glial cell line
derived neurotrophic factor.
AB - Glial cell line-derived neurotrophic factor markedly enhances survival of
neonatal dorsal root sensory neurons in vitro, an effect seen even in the
presence of anti-nerve growth factor. Furthermore, it increases levels of
substance P, inducing more than a sixfold rise that is maximal at 10 ng/ml. At
the same dose, it potentiates the action of nerve growth factor on substance P
but not on survival. Neither factor increases somatostatin content in neonatal
neurons. Although its effect on substance P diminishes with age, glial cell line
derived neurotrophic factor dramatically increases somatostatin levels in neurons
from adult rats. Glial cell line-derived neurotrophic factor is therefore the
second trophic factor found to promote survival and regulate substance P in
neonatal sensory neurons. More significant is that it is the first and sole
neurotrophic factor reported to regulate somatostatin in sensory neurons at any
age, with its effect restricted to the adult. These results suggest mechanisms
for differential regulation of somatostatin versus substance P in nociceptive
pathways.
PMID- 9648864
TI - Src homology domains of phospholipase C gamma1 inhibit nerve growth factor
induced differentiation of PC12 cells.
AB - Phospholipase C gamma1 (PLC-gamma1) is phosphorylated on treatment of cells with
nerve growth factor (NGF). To assess the role of PLC-gamma1 in mediating the
neuronal differentiation induced by NGF treatment, we established PC12 cells that
overexpress whole PLC-gamma (PLC-gamma1PC12), the SH2-SH2-SH3 domain (PLC
gamma1SH223PC12), SH2-SH2-deleted mutants (PLC-gamma1deltaSH22PC12), and SH3
deleted mutants (PLC-gamma1deltaSH3PC12). Overexpressed whole PLC-gamma1 or the
SH2-SH2-SH3 domain of PLC-gamma1 stimulated cell growth and inhibited NGF-induced
neurite outgrowth of PC12 cells. However, cells expressing PLC-gamma1 lacking the
SH2-SH2 domain or the SH3 domain had no effect on NGF-induced neuronal
differentiation. Overexpression of intact PLC-gamma1 resulted in a threefold
increase in total inositol phosphate accumulation on treatment with NGF. However,
overexpression of the SH2-SH2-SH3 domain of PLC-gamma1 did not alter total
inositol phosphate accumulation. To investigate whether the SH2-SH2-SH3 domain of
PLC-gamma1 can mediate the NGF-induced signal, tyrosine phosphorylation of the
SH2-SH2-SH3 domain of PLC-gamma1 on NGF treatment was examined. The SH2-SH2-SH3
domain of PLC-gamma1 as well as intact PLC-gamma1 could be tyrosine
phosphorylated on NGF treatment. These results indicate that the overexpressed
SH2-SH2-SH3 domain of PLC-gamma1 can block the differentiation of PC12 cells
induced by NGF and that the inhibition appears not to be related to the lipase
activity of PLC-gamma1 but to the SH2-SH2-SH3 domain of PLC-gamma1.
PMID- 9648865
TI - Evidence for activation of caspase-3-like protease in excitotoxin- and
hypoxia/hypoglycemia-injured neurons.
AB - Caspase activation has been shown to be a critical step in several models of
neuronal apoptosis such as staurosporine treatment of human neuroblastoma SH-SY5Y
cells and potassium deprivation of rat cerebellar granule neurons. One common
event is the appearance of caspase-mediated 120-kDa nonerythroid alpha-spectrin
breakdown product (SBDP120). Second, inhibitors of the caspase family are
effective blockers of such neuronal death. In this study, we report the
appearance of caspase-mediated SBDP120 in excitotoxin-challenged fetal rat
cerebrocortical neurons [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5
methyl-4-isoxazolepropionic acid, and kainate] and rat cerebellar granule neurons
(NMDA and kainate). A general caspase inhibitor, carbobenzoxy-Asp-CH2OC(O)-2,6
dichlorobenzene (Z-D-DCB), blocked the formation of SBDP120 under these
conditions and attenuated the observed NMDA-induced lactate dehydrogenase (LDH)
release in both cell types. Furthermore, hydrolytic activity toward a caspase-3
preferred synthetic peptide substrate, acetyl-DEVD-7-amido-4-methylcoumarin, was
significantly elevated in NMDA-treated granule neurons. Lastly, oxygen-glucose
deprivation (OGD)-challenged cerebrocortical cultures also showed the appearance
of SBDP120. Again, Z-D-DCB blocked the SBDP120 formation as well as attenuated
the LDH release from the OGD-challenged neurons. Taken together, the presence of
caspase-specific SBDP120 and the neuroprotective effects of Z-D-DCB strongly
suggest that caspase activation contributes at least in part to excitotoxin- and
OGD-induced neuronal death.
PMID- 9648866
TI - Ethanol induces apoptosis in cerebellar granule neurons by inhibiting insulin
like growth factor 1 signaling.
AB - The ability of ethanol to interfere with insulin-like growth factor 1 (IGF-1)
mediated cell survival was examined in primary cultured cerebellar granule
neurons. Cells underwent apoptosis when switched from medium containing 25 mM K+
to one containing 5 mM K+. IGF-1 protected granule neurons from apoptosis in
medium containing 5 mM K+. Ethanol inhibited IGF-1-mediated neuronal survival but
did not inhibit IGF-1 receptor binding or the neurotrophic action of elevated K+,
and failed to potentiate cell death in the presence of 5 mM K+. Inhibition of
neuronal survival by ethanol was not reversed by increasing the concentration of
IGF-1. Significant inhibition by ethanol (15-20%) was observed at 1 mM and was
half-maximal at 45 mM. The inhibition of IGF-1 protection by ethanol corresponded
to a marked reduction in the phosphorylation of insulin receptor substrate 1, the
binding of phosphatidylinositol 3-kinase (PI 3-kinase), and a block of IGF-1
stimulated PI 3-kinase activity. The neurotrophic response of IGF-1 was also
inhibited by the PI 3-kinase inhibitor LY294002, the protein kinase C inhibitor
chelerythrine chloride, and the protein kinase A inhibitor KT5720, but unaffected
by the mitogen-activated protein kinase kinase inhibitor PD 98059. These data
demonstrate that ethanol promotes cell death in cerebellar granule neurons by
inhibiting the antiapoptotic action of IGF-1.
PMID- 9648867
TI - Endothelin-stimulated capacitative calcium entry in enteric glial cells:
synergistic effects of protein kinase C activity and nitric oxide.
AB - Depletion of intracellular calcium stores by agonist stimulation is coupled to
calcium influx across the plasma membrane, a process termed capacitative calcium
entry. Capacitative calcium entry was examined in cultured guinea pig enteric
glial cells exposed to endothelin 3. Endothelin 3 (10 nM) caused mobilization of
intracellular calcium stores followed by influx of extracellular calcium. This
capacitative calcium influx was inhibited by Ni2+ (89 +/- 2%) and by La3+ (78 +/-
2%) but was not affected by L-, N-, or P-type calcium channel blockers.
Chelerythrine, a specific antagonist of protein kinase C, dose-dependently
inhibited capacitative calcium entry. The nitric oxide synthase inhibitor NG
nitro-L-arginine decreased calcium influx in a dose-dependent manner. The
combination of chelerythrine and NG-nitro-L-arginine produced synergistic
inhibitory effects. Capacitative calcium entry occurs in enteric glial cells via
lanthanum-inhibitable channels through a process regulated by protein kinase C
and nitric oxide.
PMID- 9648868
TI - Inhibition of phosphorylation of TrkB and TrkC and their signal transduction by
alpha2-macroglobulin.
AB - Monoamine-activated alpha2-macroglobulin (alpha2M) was shown to reduce the
dopamine concentration in corpus striatum of adult rat brains and inhibit other
neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor,
neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for
dopaminergic neurons, the effect of monoamine-activated alpha2M on signal
transduction by trkB and trkC was investigated. The results show that monoamine
activated alpha2M binds to trkB and inhibits brain-derived neurotrophic
factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent
manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma SH
SY5Y cells. Monoamine-activated alpha2M also blocks tyrosine phosphorylation of
phospholipase C-gamma1 and extracellular signal-regulated protein kinase (ERK)-1,
which are key intracellular proteins involved in trkB signal transduction.
Similarly, monoamine-activated alpha2M inhibits tyrosine phosphorylation of
neurotrophin-3-induced trkC and its signal transduction in a dose-dependent
manner in NIH3T3 cells expressing trkC (NIH3T3-trkC). In contrast to monoamine
activated alpha2M, normal alpha2M has little or no significant inhibitory effect
on the phosphorylation of trkB and trkC. In addition, the retinoic acid-promoted
tyrosine phosphorylation of phospholipase C-gamma1, ERK-1, and/or ERK-2 in SH
SY5Y cells was unaffected by monoamine-activated alpha2M; this suggests that the
inhibitory effect of activated alpha2M on the neurotrophin-stimulated
phosphorylation of intracellular signalling proteins may be specific. Taken
together, the data indicate that activated alpha2M is a pan-trk inhibitor, which
by virtue of its binding to trk receptors may block trk-mediated signal
transduction in dopaminergic neurons and lead to reduction of dopamine
concentration in corpus striatum.
PMID- 9648869
TI - Cyclopentyladenosine-induced homologous down-regulation of A1 adenosine receptors
(A1AR) in intact neurons is accompanied by receptor sequestration but not a
reduction in A1AR mRNA expression or G protein alpha-subunit content.
AB - We showed previously that exposure of cerebellar granule cells to the A1
adenosine receptor (A1AR)-selective agonist, cyclopentyladenosine, decreases A1AR
density and G protein coupling corresponding to blunted agonist-induced adenylyl
cyclase (EC 4.6.1.1) inhibition. We have now determined that A1AR-mediated
adenylyl cyclase inhibition was desensitized in a homologous manner. Carbachol-
and baclofen-induced inhibition of adenylyl cyclase was unaffected by 48-h
exposure to 10 microM cyclopentyladenosine. Expression of G protein alpha
subunits was not affected dramatically by agonist exposure. The fraction of
sequestered A1AR was increased significantly at 4, 24, and 48 h of
cyclopentyladenosine exposure (35, 57, and 81% increase over control,
respectively). The time course of agonist-induced A1AR sequestration was slower
than that reported for other G protein-coupled receptors. Incubation with the
adenosine receptor antagonist, 8-p-sulfophenyltheophylline or adenosine deaminase
did not alter sequestration significantly. Neither steady-state A1AR mRNA levels
nor transcript stability was affected by 48-h agonist exposure. We determined
that A1AR half-life in cerebellar granule cells is 20.9 h, which is considerably
longer than that reported for several other G protein-coupled receptors. The slow
time course of A1AR sequestration and the stability of the corresponding mRNA may
be a reflection of the tonic inhibitory tone exerted by adenosine in brain.
PMID- 9648870
TI - Distinct differences between morphine- and [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin
mu-opioid receptor complexes demonstrated by cyclic AMP-dependent protein kinase
phosphorylation.
AB - The present study demonstrates a conditional, agonist-dependent phosphorylation
of the mu-opioid receptor (MOR-1) by cyclic AMP-dependent protein kinase (PKA) in
membrane preparations of MOR-1-transfected neuroblastoma Neuro2A cells. Opioid
agonist-dependent phosphorylation occurs in a time- and concentration-dependent
manner (EC50 approximately 40 nM) and can be abolished by the receptor antagonist
naloxone. Stoichiometric analysis indicates incorporation of a maximum of 6 mol
of phosphate/mol of receptor in the presence of 1 microM morphine and 6 nM PKA.
Although morphine and related alkaloids as well as some peptide agonists (PLO17
and beta-endorphin) stimulated phosphorylation of MOR-1 by PKA, the potent mu
opioid-selective peptide [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) or other
enkephalin analogues such as [D-Ala2]-Met5-enkephalinamide (DALA), [D-Ala2,D
Leu5]-enkephalin (DADLE), and Met5-enkephalin had no effect. The lack of the
effect of DAMGO on MOR-1 phosphorylation state was evident also after chronic
pretreatment. These results suggest the existence of different agonist-dependent
conformations of MOR-1. Furthermore, phosphorylation may be a useful parameter
with which to identify different agonist-receptor conformations.
PMID- 9648871
TI - Tissue transglutaminase is an in situ substrate of calpain: regulation of
activity.
AB - Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes the
transamidation of specific polypeptide-bound glutamine residues, a reaction that
is inhibited by GTP. There is also preliminary evidence that, in situ, calpain
and GTP may regulate tTG indirectly by modulating its turnover by the calcium
activated protease calpain. In the present study, the in vitro and in situ
proteolysis of tTG by calpain, and modulation of this process by GTP, was
examined. tTG is an excellent substrate for calpain and is rapidly degraded.
Previously it has been demonstrated that GTP binding protects tTG from
degradation by trypsin. In a similar manner, guanosine-5'-O-(3-thiotriphosphate)
protects tTG against proteolysis by calpain. Treatment of SH-SY5Y cells with 1 nM
maitotoxin, which increases intracellular calcium levels, resulted in a
significant increase in in situ TG activity, with only a slight decrease in tTG
protein levels. In contrast, when GTP levels were depleted by pretreating the
cells with tiazofurin, maitotoxin treatment resulted in an approximately 50%
decrease in tTG protein levels, and a significant decrease in TG activity,
compared with maitotoxin treatment alone. Addition of calpain inhibitors
inhibited the degradation of tTG in response to the combined treatment of
maitotoxin and tiazofurin and resulted in a significant increase in in situ TG
activity. These studies indicate that tTG is an endogenous substrate of calpain
and that GTP selectively inhibits the degradation of tTG by calpain.
PMID- 9648872
TI - Pertussis toxin modification of PC12 cells inhibits a protein phosphatase 2A-like
phosphatase.
AB - We have found that modification of rat PC12 cells with pertussis toxin resulted
in an approximately 50% inhibition of a protein phosphatase 2A-like phosphatase.
Protein phosphatase 2A (PP2A) is a major cellular serine/threonine-specific
protein phosphatase. Treatment of extracts from pertussis toxin-modified PC12
cells with either immobilized alkaline phosphatase or Ca2+ reversed this
inhibition. Reactivation of the PP2A-like phosphatase in Ca2+ appears to result
from the dephosphorylation of a protein by the Ca2+/calmodulin-dependent protein
phosphatase calcineurin. The PP2A-like phosphatase in extracts from pertussis
toxin-modified PC12 cells eluted from a Mono Q column at a higher ionic strength
than did the PP2A-like phosphatase in extracts from control cells. After
incubation in Ca2+, the PP2A-like phosphatase in extracts from pertussis toxin
modified cells eluted from a Mono Q column at the same ionic strength as did the
PP2A-like phosphatase in extracts from control cells. These results indicate that
the effect of pertussis toxin on this PP2A-like activity results from the
phosphorylation of either one of the subunits of the PP2A-like phosphatase or a
protein that when phosphorylated binds to and inhibits this phosphatase.
Pertussis toxin modification did not result in the phosphorylation of the
catalytic subunit of PP2A. Because phosphorylation regulates the activities of
many enzymes and cell surface receptors, a pertussis toxin-induced decrease in
PP2A activity could alter signaling pathways and other cellular processes in
which G proteins are not directly involved.
PMID- 9648873
TI - Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine
from rat striatal synaptic vesicles: comparison with d-amphetamine.
AB - Lobeline, an alkaloid from Indian tobacco (Lobelia inflata), is classified as a
nicotinic agonist and is currently used as a smoking cessation agent. However,
our previous in vitro studies demonstrate that lobeline does not act as a
nicotinic agonist but alters presynaptic dopamine (DA) storage by potently
inhibiting DA uptake into synaptic vesicles. Recently, d-amphetamine has been
reported to act at the level of the synaptic vesicle to alter presynaptic
function. The present in vitro studies further elucidate the mechanism of
lobeline's action and compare its effects with those of d-amphetamine.
[3H]Dihydrotetrabenazine ([3H]DTBZ), used routinely to probe a high-affinity
binding site on the vesicular monoamine transporter (VMAT2), bound to vesicle
membranes from rat striatum with a KD of 1.67 nM and Bmax of 8.68 pmol/mg of
protein. Lobeline inhibited [3H]DTBZ binding with an IC50 of 0.90 microM,
consistent with its previously reported IC50 of 0.88 microM for inhibition of
[3H]DA uptake into vesicles. These results suggest that lobeline specifically
interacts with DTBZ sites on VMAT2 to inhibit DA uptake into synaptic vesicles.
Interestingly, d-amphetamine inhibited [3H]DTBZ binding to vesicle membranes with
an IC50 of 39.4 microM, a concentration 20 times greater than reported for
inhibition of VMAT2 function, suggesting that d-amphetamine interacts with a
different site than lobeline on VMAT2 to inhibit monoamine uptake. Kinetic
analysis of [3H]DA release from [3H]DA-preloaded synaptic vesicles in the absence
of drug revealed a t1/2 of 2.12 min. Lobeline and d-amphetamine evoked [3H]DA
release with EC50 values of 25.3 and 2.22 microM, respectively. At a
concentration 10 times the EC50, lobeline and d-amphetamine significantly
decreased the t1/2 of [3H]DA release to 1.58 and 1.48 min, respectively. Thus, in
contrast to d-amphetamine, which is equipotent in inhibiting DA uptake and
promoting release from the synaptic vesicles, lobeline more potently (28-fold)
inhibits DA uptake (via an interaction with the DTBZ site on VMAT2) than it
evokes DA release to redistribute presynaptic DA storage.
PMID- 9648874
TI - Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of
cyclic GMP, glutamate, and GABA.
AB - We have previously shown that the basal acetylcholine release in the ventral
striatum is under the enhancing influence of endogenous nitric oxide (NO) and
that NO donors cause pronounced increases in the acetylcholine release rate. To
investigate the role of cyclic GMP, glutamate, and GABA in the NO-induced
acetylcholine release, we superfused the nucleus accumbens, (Nac) of the
anesthetized rat with various compounds through a push-pull cannula and
determined the neurotransmitter released in the perfusate. Superfusion of the Nac
with the NO donors diethylamine/NO (DEANO; 100 micromol/L), S-nitroso-N
acetylpenicillamine (SNAP; 200 micromol/L), or 3-morpholinosydnonimine (SIN-1;
200 micromol/L) enhanced the acetylcholine release rate. The guanylyl cyclase
inhibitor 1H-(1,2,4)-oxodiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L)
abolished the effects of DEANO and SIN-1. 6-(Phenylamino)-5,8-quinolinedione (LY
83583; 100 micromol/L), which also inhibits cyclic GMP synthesis, inhibited the
releasing effects of DEANO and of SNAP, whereas the effect of SIN-1 on
acetylcholine release was not influenced. The DEANO-induced release of
acetylcholine was also abolished in the presence of 20 micromol/L 6,6
dinitroquinoxaline-2,3-dione (DNQX) and 10 micromol/L (+/-)-2-amino-5
phosphonopentanoic acid (AP-5). Simultaneous superfusion with 50 micromol/L
quinpirole and 10 micromol/L 7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
tetrahydro-1H-3-benzazepine (SKF 83566) was ineffective. Superfusion with 500
micromol/L DEANO decreased the release of acetylcholine. The inhibitory effect of
500 micromol/L DEANO was reversed to an enhanced release on superfusion with 20
micromol/L bicuculline. Bicuculline also enhanced the basal release rate. These
findings indicate that cyclic GMP mediates the NO-induced release of
acetylcholine by enhancing the outflow of glutamate. Dopamine is not involved in
this process. Only high concentrations of NO increase the output of GABA, which
in turn decreases acetylcholine release. Our results suggest that cells that are
able to release glutamate, such as glutamatergic neurons, are the main target of
NO in the Nac.
PMID- 9648875
TI - Regulation of extracellular dopamine by the norepinephrine transporter.
AB - There is growing evidence of an interaction between dopamine and norepinephrine.
To test the hypothesis that norepinephrine terminals are involved in the uptake
and removal of dopamine from the extracellular space, the norepinephrine uptake
blocker desmethylimipramine (DMI) was infused locally while the extracellular
concentrations of dopamine were simultaneously monitored. DMI increased the
extracellular concentrations of dopamine in the medial prefrontal cortex and
nucleus accumbens shell but had no effect in the striatum. The combined systemic
administration of haloperidol and the local infusion of DMI produced an augmented
increase in extracellular dopamine in the cortex compared with the increase
produced by either drug alone. This synergistic increase in dopamine overflow is
likely due to the combination of impulse-mediated dopamine release produced by
haloperidol and blockade of the norepinephrine transporter. No such synergistic
effects were observed in the nucleus accumbens and striatum. Local perfusion of
the alpha2-antagonist idazoxan also increased the extracellular concentrations of
dopamine in the cortex. Although the stimulation of extracellular dopamine by
idazoxan and DMI could be due to the increased extracellular concentrations of
norepinephrine produced by these drugs, an increase in dopamine also was observed
in lesioned rats that were depleted of norepinephrine and challenged with
haloperidol. This contrasted with the lack of an effect of haloperidol on
cortical dopamine in unlesioned controls. These results suggest that
norepinephrine terminals regulate extracellular dopamine concentrations in the
medial prefrontal cortex and to a lesser extent in the nucleus accumbens shell
through the uptake of dopamine by the norepinephrine transporter.
PMID- 9648876
TI - Metabolic dysfunction in familial, but not sporadic, amyotrophic lateral
sclerosis.
AB - Autosomal dominant familial amyotrophic lateral sclerosis (FALS) is associated
with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Previous
studies have implicated the involvement of metabolic dysfunction in ALS
pathogenesis. To further investigate the biochemical features of FALS and
sporadic ALS (SALS), we examined SOD activity and mitochondrial oxidative
phosphorylation enzyme activities in motor cortex (Brodmann area 4), parietal
cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients
with and without known SOD mutations, SALS patients, and disease controls (Pick's
disease, progressive supranuclear palsy, diffuse Lewy body disease). Cytosolic
SOD activity, predominantly Cu/Zn SOD, was decreased approximately 50% in all
regions in FALS patients with SOD mutations but was not significantly altered in
other patient groups. Marked increases in complex I and II-III activities were
seen in FALS patients with SOD mutations but not in SALS patients. We also
measured electron transport chain enzyme activities in a transgenic mouse model
of FALS. Complex I activity was significantly increased in the forebrain of 60
day-old G93A transgenic mice overexpressing human mutant SOD1, relative to levels
in transgenic wild-type animals, supporting the hypothesis that the motor neuron
disorder associated with SOD1 mutations involves a defect in mitochondrial energy
metabolism.
PMID- 9648877
TI - Ornithine decarboxylase in human brain: influence of aging, regional
distribution, and Alzheimer's disease.
AB - Although experimental animal data have implicated ornithine decarboxylase, a key
regulatory enzyme of polyamine biosynthesis, in brain development and function,
little information is available on this enzyme in normal or abnormal human brain.
We examined the influence, in autopsied human brain, of postnatal development and
aging, regional distribution, and Alzheimer's disease on the activity of
ornithine decarboxylase. Consistent with animal data, human brain ornithine
decarboxylase activity was highest in the perinatal period, declining sharply (by
approximately 60%) during the first year of life to values that remained
generally unchanged up to senescence. In adult brain, a moderately heterogeneous
regional distribution of enzyme activity was observed, with high levels in the
thalamus and occipital cortex and low levels in cerebellar cortex and putamen. In
the Alzheimer's disease group, mean ornithine decarboxylase activity was
significantly increased in the temporal cortex (+76%), reduced in occipital
cortex (-70%), and unchanged in hippocampus and putamen. In contrast, brain
enzyme activity was normal in patients with the neurodegenerative disorder
spinocerebellar ataxia type I. Our demonstration of ornithine decarboxylase
activity in neonatal and adult human brain suggests roles for ornithine
decarboxylase in both developing and mature brain function, and we provide
further evidence for the involvement of abnormal polyamine system activity in
Alzheimer's disease.
PMID- 9648878
TI - Pramipexole reduces reactive oxygen species production in vivo and in vitro and
inhibits the mitochondrial permeability transition produced by the parkinsonian
neurotoxin methylpyridinium ion.
AB - Sporadic Parkinson's disease is associated with a defect in the activity of
complex I of the mitochondrial electron transport chain. This electron transport
chain defect is transmitted through mitochondrial DNA, and when expressed in host
cells leads to increased oxygen free radical production, increased antioxidant
enzyme activities, and increased susceptibility to programmed cell death.
Pramipexole, a chemically novel dopamine agonist used for the treatment of
Parkinson's disease symptoms, possesses antioxidant activity and is
neuroprotective toward substantia nigral dopamine neurons in hypoxic-ischemic and
methamphetamine models. We found that pramipexole reduced the levels of oxygen
radicals produced by methylpyridinium ion (MPP+) both when incubated with SH-SY5Y
cells and when perfused into rat striatum. Pramipexole also exhibited a
concentration-dependent inhibition of opening of the mitochondrial transition
pore induced by calcium and phosphate or MPP+. These results suggest that
pramipexole may be neuroprotective in Parkinson's disease by attenuating
intracellular processes such as oxygen radical generation and the mitochondrial
transition pore opening, which are associated with programmed cell death.
PMID- 9648879
TI - Oxidative damage to proteins, lipids, and DNA in cortical brain regions from
patients with dementia with Lewy bodies.
AB - Dementia with Lewy bodies (DLB) forms the second most common pathological
subgroup of dementia after Alzheimer's disease. The present study compares the
levels of oxidative damage to proteins, lipids, and DNA bases in cortical brain
areas from patients with DLB with levels in matched control tissues. Overall,
there was a trend for protein carbonyl levels to be increased in all areas, but a
significant difference was found only in the parietal and temporal lobes. No
differences were observed in the levels of lipid peroxidation. Measurement of
products of damage to DNA bases showed increased levels of thymine glycol, 8
hydroxyguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 5-hydroxycytosine, 5
hydroxyuracil, 5-hydroxymethyluracil, and xanthine. Xanthine levels were
increased in the DLB group in the parietal, occipital, and temporal lobes,
indicating that peroxynitrite or other deaminating species may be involved. The
finding of increased protein carbonyls and increased DNA base products in
cortical regions from DLB patients indicates that oxidative stress may play a
role in DLB.
PMID- 9648880
TI - Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of
amyloid beta-protein 42 in the brain.
AB - The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of
autosomal dominant familial Alzheimer's disease (AD) in the Volga German
families. We have generated transgenic mouse lines overexpressing human wild-type
or mutant PS2 under transcriptional control of the chicken beta-actin promoter.
In the brains of transgenic mice, the levels of human PS2 mRNA were found to be
five- to 15-fold higher than that of endogenous mouse PS2 mRNA. The amyloid beta
protein (Abeta) 42 levels in the brains of mutant PS2 transgenic mice were higher
than those in wild-type PS2 transgenic mice at the age of 2, 5, or 8 months. In
addition, the Abeta42 levels appeared to increase steadily in the mutant PS2
transgenic mouse brains from 2 to 8 months of age, whereas there was only a small
increase in wild-type transgenic mice between the ages of 5 and 8 months. There
was no definite difference in the levels of N-terminal and C-terminal fragments
between wild-type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months.
These data show a definite effect of the PS2 mutation on an age-dependent
increase of Abeta42 content in the brain.
PMID- 9648881
TI - Enzymatic and molecular biological analysis of palmitoyl protein thioesterase
deficiency in infantile neuronal ceroid lipofuscinosis.
AB - Infantile neuronal ceroid lipofuscinosis (INCL) is a neurodegenerative lysosomal
storage disease that results from a deficiency of palmitoyl protein thioesterase
(PPT), a deacylating enzyme that removes cysteine-bound palmitate from proteins.
We developed an in vitro PPT enzyme assay that can be readily used for the
clinical diagnosis of both INCL patients and carriers. The substrate is a
palmitoylated peptide (IRY[14C]palmitoyl-CWLRR) synthesized by reacting [14C]
palmitoyl-CoA with a synthetic octapeptide from the PNS P0 glycoprotein. The PPT
assay performed in immortalized lymphoblastoid B-cells or the postmortem brain
homogenate showed the optimal enzyme activity at pH 5.0, consistent with the
findings that PPT is a lysosomal enzyme. PPT activity in lymphoblasts from INCL
patients was <4% of that of control lymphoblasts. In addition, obligatory
carriers showed 74% of the control activity. Other pathological controls,
including the juvenile form of NCL, showed PPT activities that were not different
from normal. Furthermore, one brain sample from an INCL patient contained only 7%
PPT activity when compared with an unaffected brain. Thus, the enzyme activity
assay gives a confident diagnosis of INCL. In contrast, when the total RNA
extract from lymphoblasts was probed with 32P-labeled PPT by northern blot
analysis, the level of transcript varied among independent INCL families and was
not related to PPT activity. In conclusion, whereas variant genetic modifications
result in PPT deficiency, all giving similar INCL phenotype, both affected
patients and heterozygote carriers can now be screened with a reliable in vitro
PPT assay.
PMID- 9648882
TI - Lactate is released and taken up by isolated rabbit vagus nerve during aerobic
metabolism.
AB - To determine if lactate is produced during aerobic metabolism in peripheral
nerve, we incubated pieces of rabbit vagus nerve in oxygenated solution
containing D-[U-14C]glucose while stimulating electrically. After 30 min, nearly
all the radioactivity in metabolites in the nerve was in lactate, glucose 6
phosphate, glutamate, and aspartate. Much lactate was released to the bath: 8.2
pmol (microg dry wt)(-1) from the exogenous glucose and 14.2 pmol (microg dry
wt)(-1) from endogenous substrates. Lactate release was not increased when bath
PO2 was decreased, indicating that it did not come from anoxic tissue. When the
bath contained [U-14C]lactate at a total concentration of 2.13 mM and 1 mM
glucose, 14C was incorporated in CO2 and glutamate. The initial rate of formation
of CO2 from bath lactate was more rapid than its formation from bath glucose. The
results are most readily explained by the hypothesis that has been proposed for
brain tissue in which glial cells supply lactate to neurons.
PMID- 9648883
TI - Expression pattern of synucleins (non-Abeta component of Alzheimer's disease
amyloid precursor protein/alpha-synuclein) during murine brain development.
AB - The non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP)
is predominantly a neuron-specific presynaptic protein that may play a central
role in neurodegeneration because NACP fragments are found in Alzheimer's disease
amyloid and a mutation in the NACP gene is associated with familial Parkinson's
disease. In addition, NACP may play an important role during synaptogenesis and
CNS development. To understand better the patterns of NACP expression during
development, we analyzed the levels of this protein as well as the levels of
another synaptic protein (synaptophysin) by ribonuclease protection assay,
western blotting, and immunocytochemistry in fetal, juvenile, and adult mouse
brain. From embryonic day 12 to 15, there was a slight increase, which was then
followed by a more dramatic increase at later time points. Immunocytochemical
staining for NACP increases throughout these stages as well. Although NACP
appeared early in CNS development, synaptophysin levels started to rise at a
later stage. These findings support the contention that NACP might be important
for CNS development. Furthermore, the cytosolic component of NACP precedes the
particulate component in development, indicating that a redistribution of the
protein to the membrane fraction may be important for events later in neuronal
development and in synaptogenesis.
PMID- 9648884
TI - Immunohistochemical localization of G protein beta1, beta2, beta3, beta4, beta5,
and gamma3 subunits in the adult rat brain.
AB - The regional distributions of the G protein beta subunits (Gbeta1-beta5) and of
the Ggamma3 subunit were examined by immunohistochemical methods in the adult rat
brain. In general, the Gbeta and Ggamma3 subunits were widely distributed
throughout the brain, with most regions containing several Gbeta subunits within
their neuronal networks. The olfactory bulb, neocortex, hippocampus, striatum,
thalamus, cerebellum, and brainstem exhibited light to intense Gbeta
immunostaining. Negative immunostaining was observed in cortical layer I for
Gbeta1 and layer IV for Gbeta4. The hippocampal dentate granular and CA1-CA3
pyramidal cells displayed little or no positive immunostaining for Gbeta2 or
Gbeta4. No anti-Gbeta4 immunostaining was observed in the pars compacta of the
substantia nigra or in the cerebellar granule cell layer and Purkinje cells.
Immunoreactivity for Gbeta1 was absent from the cerebellar molecular layer, and
Gbeta2 was not detected in the Purkinje cells. No positive Ggama3
immunoreactivity was observed in the lateral habenula, lateral septal nucleus, or
Purkinje cells. Double-fluorescence immunostaining with anti-Ggamma3 antibody and
individual anti-Gbeta1-beta5 antibodies displayed regional selectivity with
Gbeta1 (cortical layers V-VI) and Gbeta2 (cortical layer I). In conclusion,
despite the widespread overlapping distributions of Gbeta1-beta5 with Ggamma3,
specific dimeric associations in situ were observed within discrete brain
regions.
PMID- 9648885
TI - Synaptic vesicle protein SV2B, but not SV2A, is predominantly expressed and
associated with microvesicles in rat pinealocytes.
AB - Microvesicles are endocrine counterparts of neuronal synaptic vesicles, and
accumulate and secrete classic neurotransmitters. In mammalian pinealocytes,
microvesicles accumulate L-glutamate through a vesicular glutamate transporter
and secrete it through exocytosis. To characterize the molecular organization of
microvesicles in more detail, we investigated in this study the expression and
localization of synaptic vesicle protein 2 (SV2) in rat pinealocytes. RT-PCR
analysis indicated that transcripts specific for two isoforms, SV2A, a ubiquitous
form present in neuronal and endocrine cells, and SV2B, a neuron-specific form,
are amplified in pineal RNAs. Northern blotting with specific transcripts
indicated that the mRNA for SV2B is predominantly expressed, whereas that for
SV2A is below the detection limit. Site-specific antibodies against SV2B
recognized a single 72-kDa polypeptide in the pineal membrane fraction, whereas
anti-SV2A antibodies did not recognize any polypeptides. Immunohistochemical
analysis of cultured cells indicated that SV2B is expressed in pinealocytes but
not in other types of cells. SV2B is present in somata and is especially rich in
processes, which are filled with microvesicles. SV2B is colocalized with
synaptophysin and synaptotagmin, markers for microvesicles. Immunoelectron
microscopy indicated that SV2B is associated with microvesicles. These results
indicated that SV2B, but not SV2A, is expressed in rat pinealocytes and
associated with microvesicles. As SV2B is also expressed in cultured alphaTC6
clonal pancreatic a cells, SV2B is not a protein specific for neurons.
PMID- 9648886
TI - Ceramide and its interconvertible metabolite sphingosine function as
indispensable lipid factors involved in survival and dendritic differentiation of
cerebellar Purkinje cells.
AB - Ceramide generated from sphingomyelin has emerged as a new but conserved type of
biologically active lipid. We previously found that endogenous sphingolipids are
required for the normal growth of cultured cerebellar Purkinje neurons and that
sphingomyelin is present abundantly in the somatodendritic region of these cells.
To gain further insight into a potential role of the sphingomyelin/ceramide
pathway, we investigated the effects of depletion of sphingolipids on the
phenotypic growth and survival of immature Purkinje cells and the ability of
ceramide or other sphingolipids to antagonize these effects. Inhibition of
ceramide synthesis by ISP-1, a specific inhibitor of serine palmitoyltransferase,
decreased cellular levels of sphingolipids. This treatment resulted in a decrease
in cell survival accompanied by an induction of apoptotic cell death and aberrant
dendritic differentiation of Purkinje cells with no detectable changes in other
cerebellar neurons. Cell-permeable ceramides, sphingosine, or sphingomyelin
overcame these abnormalities more effectively than other sphingolipids when added
simultaneously with ISP-1. Exposure to bacterial sphingomyelinase in turn
enhanced cell survival and dendritic branching complexity of Purkinje cells at
different optimal concentrations. Furthermore, cell-permeable ceramide acted
synergistically with the neurotrophin family, which has been previously shown to
support Purkinje cell survival. These observations suggest that ceramide is a
requisite for the survival and the dendritic differentiation of Purkinje cells.
PMID- 9648887
TI - Regulation of Drosophila Ca2+/calmodulin-dependent protein kinase II by
autophosphorylation analyzed by site-directed mutagenesis.
AB - In this study we demonstrate that Drosophila calcium/calmodulin-dependent protein
kinase II (CaMKII) is capable of complex regulation by autophosphorylation of the
three threonines within its regulatory domain. Specifically, we show that
autophosphorylation of threonine-287 in Drosophila CaMKII is equivalent to
phosphorylation of threonine-286 in rat alpha CaMKII both in its ability to
confer calcium independence on the enzyme and in the mechanistic details of how
it becomes phosphorylated. Autophosphorylation of this residue occurs only within
the holoenzyme structure and requires calmodulin (CaM) to be bound to the
substrate subunit. Phosphorylation of threonine-306 and threonine-307 in the CaM
binding domain of the Drosophila kinase occurs only in the absence of CaM, and
this phosphorylation is capable of inhibiting further CaM binding. Additionally,
our findings suggest that phosphorylation of threonine-306 and threonine-307 does
not mimic bound CaM to alleviate the requirement for CaM binding to the substrate
subunit for intermolecular threonine-287 phosphorylation. These results
demonstrate that the mechanism of regulatory autophosphorylation of this kinase
predates the split between invertebrates and vertebrates.
PMID- 9648888
TI - The peptide transporter PepT2 mediates the uptake of the glutathione precursor
CysGly in astroglia-rich primary cultures.
AB - The intracellular content of glutathione in astroglia-rich primary cultures
derived from the brains of newborn rats was used as an indicator for the ability
of these cultures to utilize cysteinylglycine (CysGly) for glutathione synthesis.
After a 24-h starvation period in the absence of glucose and amino acids, CysGly
was able to substitute for cysteine plus glycine in the restoration of
glutathione. Glutathione restoration from CysGly plus glutamate was only slightly
affected by the dipeptides carnosine or serylglycine in a 200-fold excess.
Captopril, a substrate of the peptide transporter PepT1, had almost no effect on
glutathione restoration. In contrast, with increasing concentrations of
alanylalanine or cefadroxil, known substrates of the peptide transporter PepT2,
the amount of glutathione restored in the presence of CysGly and glutamate was
strongly reduced. Cefadroxil in a 200-fold excess totally prevented the
utilization of CysGly for glutathione restoration. The presence of mRNA for PepT2
in astroglia-rich primary cultures was demonstrated by application of RT-PCR.
These results demonstrate that PepT2 is expressed in astroglia-rich primary
cultures and that this transporter is highly likely to be responsible for the
uptake of CysGly in these cultures.
PMID- 9648889
TI - Differential effects of increasing gestational age and placental restriction on
tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and proenkephalin A
mRNA levels in the fetal sheep adrenal.
AB - We have demonstrated that there are differential changes in the levels of
tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and
proenkephalin A (Pro Enk A) mRNA in the fetal sheep adrenal during late
gestation. Adrenal TH mRNA:18S rRNA ratios increased between gestational days 100
(0.98 +/- 0.13; n = 6) and 125 (1.40 +/- 0.15; n = 6) and then decreased, whereas
adrenal PNMT mRNA:18S rRNA ratios increased regularly between gestational days
100 (0.08 +/- 0.01) and 146 (0.17 +/- 0.03). The ratio of adrenal Pro Enk A mRNA
to 18S rRNA was higher at gestational day 125 (0.085 +/- 0.005) than at either 80
100 days (0.038 +/- 0.007) or 140-146 days of gestation (0.055 +/- 0.013). In 12
ewes, the growth and development of the placenta were restricted (placental
restriction group) from conception. The ratio of adrenal PNMT mRNA to 18S rRNA
was significantly reduced in the placental restriction group of fetal sheep
(0.003 +/- 0.002) compared with controls (0.011 +/- 0.002), and there was a
significant correlation between the ratio of adrenal PNMT mRNA to 18S rRNA and
the mean arterial PO2 (r = 0.88, p < 0.0005). In contrast, TH mRNA and Pro Enk
mRNA were unaffected by placental restriction. Adrenaline and noradrenaline
syntheses are therefore differentially regulated in the adrenal during late
gestation and in response to chronic intrauterine hypoxemia.
PMID- 9648890
TI - Manipulation of disulfide bonds differentially affects the intracellular
transport, sorting, and processing of neuroendocrine secretory proteins.
AB - To investigate if the prevention of disulfide bond formation affects the
intracellular transport, sorting, and processing of a distinct set of
neuroendocrine proteins in the regulated secretory pathway, we have treated
Xenopus intermediate pituitaries with the thiol-reducing agent dithiothreitol.
Pulse-chase incubations in combination with immunoprecipitation analysis were
used to monitor the fates of the prohormone proopiomelanocortin (POMC),
prohormone convertase PC2 and its helper protein 7B2, as well as secretogranin
III. Manipulation of the disulfide bonds in POMC and proPC2 blocked their
transport to the trans-Golgi network and strongly inhibited their processing.
Reduction of the single disulfide bond in 7B2 did not disturb its transport and
cleavage, but caused its missorting to the constitutive secretory pathway.
Moreover, the liaison between proPC2 and 7B2 was prevented. Dithiothreitol did
not affect transport, sorting, and cleavage of secretogranin III, which lacks
disulfide bonds. When the reducing agent was washed away, POMC processing, proPC2
maturation, and the association between proPC2 and 7B2 were reestablished.
Collectively, our findings indicate that manipulation of disulfide bonds
differentially affects the fates of neuroendocrine proteins during their transit
through the secretory pathway.
PMID- 9648891
TI - Phosphatidic acid-dependent phosphorylation of a 29-kDa protein by protein kinase
Calpha in bovine brain cytosol.
AB - Activation of phospholipase D (PLD) is involved in receptor-mediated signal
transduction responses. Signaling from PLD to a downstream molecule(s) appears to
be mediated by the PLD product phosphatidic acid (PA). A target molecule(s) of
PA, however, has not yet been identified. The present study sought to define such
a target molecule(s) of PA. In bovine brain cytosol, proteins with apparent
molecular weights of 29,000 (p29) and 32,000 (p32) were prominently
phosphorylated in the presence of PA, but not in its absence, indicating that
there is a PA-regulated protein kinase (PARK) in bovine brain that phosphorylates
p29 and p32. One of these substrates, p29, was purified to near homogeneity. Its
partial amino acid sequence was determined and found to be identical to that of a
known brain-specific 25-kDa protein (p25). The purified p29 was also readily
recognized by and immunoprecipitated with an anti-p25 antibody. These results
suggest that p29 is very similar to or identical with p25. Using the purified p29
as a substrate, PARK was purified to near homogeneity. The purified PARK had an
apparent molecular weight of 80,000, was strongly recognized by an antiprotein
kinase C (PKC)alpha antibody, and was activated by phosphatidylserine (PS) as
well as PA. The PA- and PS-stimulated PARK activity was extremely augmented by
the presence of 1 microM free Ca2+. In the presence of 1 mM EGTA, phorbol 12
myristate 13-acetate activated PARK synergistically with PA or PS. Similar
results were obtained with the purified recombinant PKCalpha. From these results,
it is suggested that the PARK activity purified might be attributed to PKCalpha.
In p25-depleted bovine brain cytosol, which was prepared by treatment of bovine
brain cytosol with the anti-p25 antibody, PA-dependent phosphorylation of p29,
but not p32, was almost completely eliminated. When PKCalpha in bovine brain
cytosol was depleted by its precipitation with the anti-PKCalpha antibody,
neither p29 nor p32 in this PKCalpha-depleted cytosol was phosphorylated in the
presence of PA. These results indicate that in bovine brain cytosol PA activates
PKCalpha, which, in turn, phosphorylates p29, which may be identical with p25.
PMID- 9648893
TI - Dynamic regulation of the activated, autophosphorylated state of Ca2+/calmodulin
dependent protein kinase II by acute neuronal excitation in vivo.
AB - Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated in
various neuronal functions, including synaptic plasticity. To examine the
physiological regulation of its activated, autophosphorylated state in relation
to acute neuronal excitation in vivo, we studied the effect of electroconvulsive
treatment in rats on CaMKII activity and in situ autophosphorylation levels. As
early as 30 s after the electrical stimulation, a profound but transient decrease
in its Ca2+/calmodulin-independent activity, as well as in the level of its
autophosphorylation at Thr286(alpha)/Thr287(beta) measured by using
phosphorylation state-specific antibodies, was observed in homogenate from
hippocampus and parietal cortex, which was reversible in 5 min. In the later time
course, a moderate, reversible increase, which peaked at around 60 min after the
electrical stimulation, was observed in parietal cortex but not in hippocampus.
The early-phase decrease was found to occur exclusively in the soluble fraction.
In addition, partial translocation of CaMKII from the soluble to the particulate
fraction seems to have occurred in this early phase. Thus, the activated,
autophosphorylated state of CaMKII is under dynamic and precise regulation in
vivo, and its regulatory mechanisms seem to have regional specificity.
PMID- 9648892
TI - Binding characteristics of a potent AMPA receptor antagonist [3H]Ro 48-8587 in
rat brain.
AB - A new AMPA receptor antagonist, Ro 48-8587, was characterized pharmacologically
in vitro. It is highly potent and selective for AMPA receptors as shown by its
effects on [3H]AMPA, [3H] kainate, and [3H] MK-801 binding to rat brain membranes
and on AMPA- or NMDA-induced depolarization in rat cortical wedges. [3H]Ro 48
8587 bound with a high affinity (KD = 3 nM) to a single population of binding
sites with a Bmax of 1 pmol/mg of protein in rat whole brain membranes. [3H]Ro 48
8587 binding to rat whole brain membranes was inhibited by several compounds with
the following rank order of potency: Ro 48-8587 > 6-nitro-7-sulphamoylbenzo[f]
quinoxaline-2,3-dione (NBQX) > YM 90K > 6-cyano-7-nitroquinoxaline-2,3-dione
(CNQX) > quisqualate > AMPA > glutamate > kainate > NMDA. The distribution and
abundance of specific binding sites (approximately 95% of total) in sections of
rat CNS, revealed by quantitative receptor radioautography and image analysis,
indicated a very discrete localization. Highest binding values were observed in
cortical layers (binding in layers 1 and 2 > binding in layers 3-6), hippocampal
formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar
molecular layer, and spinal cord dorsal horn. At 1 nM, the values for specific
binding were highest in the cortical layers 1 and 2 and lowest in the brainstem
(approximately 2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a
potent and selective AMPA receptor antagonist with improved binding
characteristics (higher affinity, selectivity, and specific binding) compared
with those previously reported.
PMID- 9648894
TI - Norepinephrine increases cyclic GMP levels in cerebellar cells from neuronal
nitric oxide synthase knockout mice.
AB - Cyclic GMP is an important intracellular messenger in the nervous system that may
mediate cellular forms of neuronal plasticity. Previous studies show that most
neurotransmitters stimulate cyclic GMP levels by the activation of nitric oxide
synthase (NOS). In this study, we report that in primary cell cultures from the
cerebellum of neuronal NOS knockout mice, norepinephrine stimulates an increase
in cyclic GMP content. This increase is seen in both granule cell and astrocyte
cultures and is not blocked by inhibitors of NOS or by inhibition of soluble
guanylyl cyclase. These results suggest a novel pathway by which norepinephrine
enhances cyclic GMP levels in the nervous system.
PMID- 9648895
TI - Examining amended reports in surgical pathology.
PMID- 9648896
TI - Amended reports in surgical pathology and implications for diagnostic error
detection and avoidance: a College of American Pathologists Q-probes study of
1,667,547 accessioned cases in 359 laboratories.
AB - OBJECTIVES: To evaluate amended report rates relative to surveillance methods and
to identify surveillance methods or other practice parameters that lower amended
report rates. DESIGN: Participants in the 1996 Q-Probes quality improvement
program of the College of American Pathologists were asked to prospectively
document amended surgical pathology reports for a period of 5 months or until 50
amended reports were recorded. The methods of error detection were also recorded
and laboratory and institutional policies surveyed. Four types of amended reports
were investigated: those issued to correct patient identification errors, to
revise originally issued final diagnoses, to revise preliminary written
diagnoses, and to revise other reported diagnostic information that was
significant with respect to patient management or prognosis. PARTICIPANTS: Three
hundred fifty-nine laboratories, 96% from the United States. RESULTS: A total of
3147 amended reports in all four categories from a survey of 1,667,547 surgical
pathology specimens accessioned during the study period were issued by the
participants. The aggregate mean rate of amended reports was 1.9 per 1000 cases
(median, 1.5 per 1000 cases). Of these, 19.2% were issued to correct patient
identification errors, 38.7% to change the originally issued final diagnosis,
15.6% to change a preliminary written diagnosis, and 26.5% to change clinically
significant information other than the diagnosis. Most frequently, a request from
a clinician to review a case (20.5%) precipitated the error detection. Although
not statistically significant, a higher amended report rate (1.6 per 1000) for
all error types was associated with routine diagnostic slide review that was
performed after completion of the surgical pathology report. This is compared to
rates for institutions that had routine diagnostic slide review of cases prior to
finalization of pathology reports (1.2 per 1000) and institutions that had no
routine diagnostic slide review (1.4 per 100). Slide review of cases prior to
completion of reports lowered the rate of amended reports issued for two types of
amended reports: those in which the originally issued final diagnosis was changed
and those in which information other than the diagnosis was changed for patient
management or prognostic significance. Other laboratory practice variables
examined were not found to be associated with the amended report rate.
CONCLUSIONS: There is an association between lower amended report rates and
diagnostic slide review of cases prior to completion of the pathology report. The
level of case review and type of case mix that is necessary for optimal quality
assurance needs further investigation.
PMID- 9648897
TI - Apoptosis: basic concepts and potential significance in human cancer.
AB - Numerous factors trigger or repress apoptosis (genetically mediated individual
cell death). The details of signal transduction pathways and regulation of
apoptosis by numerous oncogene and tumor suppressor gene products are not fully
understood. Bcl-2 inhibits apoptosis induction by a variety of stimuli. Caspases
are the basic effectors of apoptosis, leading ultimately to fragmentation of DNA,
at which stage apoptosis can be identified. Apoptosis affects scattered
individual cells that have extremely dense nodular, beaded, or crescentic
chromatin, and differs morphologically, biochemically, and topographically from
necrosis. Apoptosis is a negative growth-regulating mechanism in cancer, and its
extent varies with tumor type. Apoptosis reflects tumor cell kinetics; aggressive
tumors often show conspicuous apoptosis, and there are significant linear
correlations between apoptotic and mitotic indices in many tumor types. The
relative importance of p53, c-Myc, Rb, and the Bcl-2 homologs in the regulation
of apoptosis in different human cancers is not clear. Further pathologic
investigations on apoptosis in human cancer are needed to reaffirm recent
experimental findings and to explain more fully the regulation and biological
significance of apoptosis in vivo.
PMID- 9648898
TI - Evaluation of a proposed panel of cardiac markers for the diagnosis of acute
myocardial infarction in patients with atraumatic chest pain.
AB - OBJECTIVE: The purpose of this study was to evaluate retrospectively the efficacy
of a proposed panel of three cardiac markers (myoglobin, creatine kinase-MB mass
[CK-MB], and cardiac troponin I) in the diagnosis of acute myocardial infarction
(AMI) in patients with atraumatic chest pain. DESIGN: A total of 110 patients
admitted for the evaluation of atraumatic chest pain were examined. Forty-one of
these patients were diagnosed with AMI. RESULTS: Five of the 41 patients with AMI
had abnormally elevated myoglobin levels, whereas values of CK-MB and/or cardiac
troponin I remained negative. Creatine kinase-MB mass alone had a sensitivity of
92.7%, a specificity of 89.9%, a positive predictive value of 84.4%, and a
negative predictive value of 95.0% for the diagnosis of AMI. Cardiac troponin I
alone had a sensitivity of 90.2%, a specificity of 95.7%, a positive predictive
value of 92.5%, and a negative predictive value of 94.3% for the diagnosis of
AMI. Cardiac troponin I is a more specific marker for the diagnosis of AMI than
CK-MB, particularly in patients with chronic renal failure who are evaluated for
chest pain. The combination of CK-MB and cardiac troponin I increased the
sensitivity to 100% and the negative predictive value to 100% and had a
specificity of 88.4% and a positive predictive value of 83.7%. The panel was
diagnostic for all patients with AMI within 12 hours after admission.
CONCLUSIONS: Our preliminary results indicate that this panel is highly effective
for evaluation of AMI in patients with atraumatic chest pain. Elevated myoglobin
levels were useful in detecting patients at high risk for AMI who initially were
not detected with other markers. The combination of CK-MB and cardiac troponin I
provided much higher sensitivity and had a much higher negative predictive value
for the evaluation of AMI than cardiac troponin I or CK-MB alone. The 100%
negative predictive value is particularly important because it indicates that
patients with negative CK-MB and cardiac troponin I values 12 hours after
admission have a negligible likelihood of AMI.
PMID- 9648899
TI - Comparison of functional testing for resistance to activated protein C and
molecular biological testing for factor V R506Q in 370 patients.
AB - OBJECTIVE: To compare functional and molecular biological tests for resistance to
activated protein C (APC)/factor V R506Q, the most common cause of familial
thrombosis. METHODS: We developed functional and molecular biological tests for
resistance to APC/factor V R506Q at our institution and correlated the results
for 370 patients studied by both methods. The functional method is based on
addition of exogenous APC to an activated partial thromboplastin time-based
assay. The molecular biological method is based on polymerase chain reaction
followed by endonuclease digestion. RESULTS: Considering the molecular biological
test as definitive for detecting the factor V R506Q mutation, the sensitivity of
the functional assay was 100%, and the specificity was 74%. The prevalence of the
factor V mutation in the population studied was 12% (41 heterozygotes, two
homozygotes), and the positive predictive value of the functional assay was 34%.
Although a normalized sensitivity ratio (nAPC-SR) less than 0.84 is considered
evidence of resistance to APC by functional testing, we found that all patients
with factor V R506Q had an nAPC-SR less than or equal to 0.71. When this
alternative positive cutoff was used, the specificity of the functional test for
factor V R506Q increased to 87%, and the positive predictive value increased to
52%, which constituted a significant improvement. We compared clinical findings
from patients with resistance to APC with or without the presence of factor V
R506Q, and found that as a group, those with factor V R506Q had a higher
incidence of hypercoagulability, but fewer additional risk factors for
hypercoagulability. The mechanism of resistance to APC in factor V R506Q-negative
individuals is unclear, but may be related to other risk factors for
hypercoagulability. CONCLUSIONS: The functional assay for resistance to APC is an
excellent screening test for factor V R506Q, but confirmatory molecular
biological testing is necessary when the functional test is positive, because of
the high false-positive rate.
PMID- 9648900
TI - Use of age-specific normal ranges for serum prostate-specific antigen.
AB - BACKGROUND: The traditional normal range for prostate-specific antigen has been
0.0 to 4.0 ng/mL. Two different age-specific normal ranges have been proposed,
one by Oesterling et al and the other generated by the Prostate Cancer Awareness
Week experience. METHODS: We studied 213 consecutive cases of biopsy-proven
prostate adenocarcinoma to evaluate age-specific normal ranges for prostate
specific antigen. We examined each patient's age, stage of disease, and serum
concentration of prostate-specific antigen at the time of diagnosis. The three
normal ranges were applied to each case. RESULTS: The patients ranged in age from
45 to 87 years. At all stages of disease, more patients had elevated serum
prostate-specific antigen values using the traditional normal range as opposed to
either age-specific normal range. These discrepancies were most obvious for stage
II disease, in which 93 of 119 cases (78%) were elevated according to the
traditional normal range versus 78 of 119 cases (66%) according to the Oesterling
et al range and 80 of 119 cases (67%) according to the range defined during
Prostate Cancer Awareness Week. For patients aged 40 to 59 years, all three
normal ranges provided identical results (18 of 22 [82%] cancers detected).
CONCLUSIONS: Use of either age-specific normal range would have missed more than
10% of stage II prostate adenocarcinomas in patients over the age of 60 years.
This indicates that caution should be exercised when applying age-adjusted normal
ranges for serum concentrations of prostate-specific antigen in patients of that
age group.
PMID- 9648901
TI - Cytologic and genetic study of polyomavirus-infected or polyomavirus-activated
cells in human urine.
AB - OBJECTIVE: To carry out a morphologic and genetic study of human polyomavirus
infection or activation in child and adult urine specimens. DESIGN AND SETTING:
The study was carried out on 16 urine samples from children with human
polyomavirus infection and 104 samples from adults with virus activation
identified among 18800 consecutive urine samples (0.64%). RESULTS: All specimens
from children showed numerous typical intranuclear inclusion-bearing (INIB)
cells. All adult specimens with cytological features similar to childhood
specimens were defined as type 1 adult cases. We identified 14 adult cases with
marked immunologic suppression as type 1 cases. The inclusions were large,
homogeneous, and basophilic, and they were mainly attributable to the BK virus,
as demonstrated by a polymerase chain reaction. These infected or activated cells
revealed features demonstrating their origin in the superficial transitional
epithelium of the urinary tract. Adult cases with different cytologic features
were designated as type 2 adult cases. In type 2 adult cases, the number of virus
activated cells was lower, and degenerated intranuclear inclusion-bearing cells
with a coarse chromatin pattern were observed in most cases. These
characteristics were identified in 90 adults without immunologic suppression. A
polymerase chain reaction with BamHI digestion demonstrated JC virus DNA in
nearly all of these specimens. CONCLUSION: The JC virus-activated cells found in
type 2 adult cases and the BK virus-infected cells found in childhood cases were
not of clinical importance. However, the BK virus-activated cells associated with
immunologic suppression may have prognostic significance.
PMID- 9648902
TI - Qualifying the cytologic diagnosis of "atypical squamous cells of undetermined
significance" affects the predictive value of a squamous intraepithelial lesion
on subsequent biopsy.
AB - OBJECTIVE: To evaluate whether different qualifications of a cytologic diagnosis
of "atypical squamous cells of undetermined significance" predict a greater or
lesser likelihood of cervical pathology. DESIGN: Comparison of different
cytologic qualifications of atypical squamous cells of undetermined significance
with the frequency of significant cervical disease as documented by tissue
biopsy. PARTICIPANTS AND SETTING: Four hundred, fifty-two consecutive
Papanicolaou smears showing atypical squamous cells of undetermined significance
(diagnosed by nine cytopathologists) in women who had undergone cervical biopsy
within the previous 90 days at Brigham and Women's Hospital, Boston, Mass
(January-June 1995). MAIN OUTCOME MEASURE: The histopathologic diagnosis of
squamous intraepithelial lesion of the cervix. RESULTS: The 452 smears were
qualified as "favor reactive" (22%), "not otherwise specified" (42%), "favor
squamous intraepithelial lesion" (29%), and "favor high-grade squamous
intraepithelial lesion" (6%). High-grade squamous intraepithelial lesions and
total squamous intraepithelial lesions were pathologically confirmed by cervical
biopsy in 3.6% and 6% of the favor reactive smears, in 11% and 21% of the not
otherwise specified smears, in 12% and 30% of the favor squamous intraepithelial
lesion smears, and in 53% and 59% of the favor high-grade squamous
intraepithelial lesion smears. Significant associations were seen between a favor
reactive smear and a benign finding on cervical biopsy (94%, P = .04) and between
a favor high-grade squamous intraepithelial lesion smear and a biopsy that showed
a high-grade squamous intraepithelial lesion (53%, P = .00001). CONCLUSIONS:
Qualifying atypical squamous cells of undetermined significance stratifies women
into different risk groups for squamous intraepithelial lesion. It is reasonable
for physicians to make patient management decisions based, at least in part, on
such qualifications.
PMID- 9648903
TI - The histologic effects of low-dose methotrexate therapy for primary biliary
cirrhosis.
AB - OBJECTIVE: Primary biliary cirrhosis is a progressive liver disease that is
believed to be autoimmune in nature. Treatment, at best, may slow the progression
of the disease, although no therapy has been able to halt its progression.
Preliminary data suggest a beneficial effect of methotrexate in the treatment of
primary biliary cirrhosis. We evaluated the histologic effect of 2 years of
treatment with methotrexate. DESIGN: Liver biopsies were obtained before
methotrexate was started and after 2 years of therapy. Ninety-six paired biopsies
from 48 patients with primary biliary cirrhosis were reviewed by a pathologist
who was blinded to all clinical history and sequence of the biopsies. Variables
examined included stage of the disease, degree of portal fibrosis, portal
inflammation and piecemeal necrosis, bile duct injury or loss, bile ductular
proliferation, lobular inflammation and necrosis, steatosis, granulomas,
cholestasis, and nuclear pleomorphism of hepatocytes. RESULTS: In most
categories, pretreatment and posttreatment biopsies did not reflect a change over
the 2-year period of treatment. There was a trend toward progression of the stage
of the disease, portal fibrosis, bile duct loss, fat, and pleomorphism over the 2
years and toward regression in piecemeal necrosis, bile duct injury, ductular
proliferation, granulomas, and lobular inflammation and necrosis. CONCLUSION:
After 2 years of treatment with methotrexate, the stage of disease and fibrosis
of primary biliary cirrhosis continue to progress, although overall, inflammation
and bile duct injury decrease with methotrexate treatment.
PMID- 9648904
TI - Comparative study of computer-assisted image analysis and light-microscopically
determined estrogen receptor status of breast carcinomas.
AB - BACKGROUND: Efficient tamoxifen treatment of breast cancer patients depends on
the degree to which pathologists are consistently able to use the so-called
"modified quickscore" method to differentiate between negative and low-grade
positive scores based on the current four-grade scale of the estrogen receptor
(ER) status of the tumors. OBJECTIVE: To quantitatively test pathologists'
ability to adequately render correct readings of the ER status of breast tumors.
METHODS: The ER status of breast carcinomas was estimated by two pathologists and
measured by computer-supported analysis in sections stained with ER antibody by
the immunoperoxidase technique. Levels of agreement between the examiners'
semiquantification and histomorphometrically gauged measurements were compared
statistically. RESULTS: The kappa coefficients were 0.28 on a case-by-case
collation of the grades of nuclear staining, 0.52 on applying binary categories
of positively versus negatively stained cell nuclei, and 0.89 using binary
categories with a weighted score of 1.2 to separate ER-negative from ER-positive
breast carcinomas. CONCLUSIONS: The findings suggest that an optimum rating
system is achieved by assigning tumors with a weighted score of 1.2 or less to
the ER-negative and those with a weighted score of 1.3 or more to the ER-positive
category of breast carcinomas.
PMID- 9648905
TI - Glycogen-rich malignant melanomas and glycogen-rich balloon cell malignant
melanomas: frequency and pattern of PAS positivity in primary and metastatic
melanomas.
AB - OBJECTIVE: After identifying a metastatic glycogen-rich balloon cell malignant
melanoma, originally thought to be a benign clear cell tumor of the lung, we
investigated the extent of positive reactions, or "positivity," of malignant
melanoma to periodic acid-Schiff (PAS) staining. METHODS: Frequency, intensity,
and distribution of PAS positivity was studied in 61 excisional biopsy specimens
from 58 patients with malignant melanoma. For comparison, 17 benign nevi from 10
patients were examined. RESULTS: Positivity for PAS was seen in all cases. All
malignant melanomas and benign nevi were characterized by weak, diffuse, diastase
resistant PAS positivity. Additionally, focal or diffuse, strong diastase
sensitive PAS positivity was observed in 9 of 61 melanomas (15%); 7 were
metastatic and 2 were primary invasive melanomas. Strong diastase-sensitive PAS
positivity was seen in all lesions with 30% or more balloon cell features and
only in advanced primary or metastatic lesions. The presence of glycogen was
confirmed by transmission electron microscopy. CONCLUSIONS: Cutaneous malignant
melanomas have weak, diastase-resistant PAS positivity. Strong diastase-sensitive
PAS positivity, consistent with the presence of intracytoplasmic glycogen, is
seen in many primary and metastatic melanomas with balloon cell features.
Depending on the content of the balloon cells, these melanomas are best
categorized as either glycogen-rich malignant melanomas or glycogen-rich balloon
cell malignant melanomas. Because many tumors with clear cell features contain
glycogen, such content often is an unreliable differential feature.
PMID- 9648906
TI - Primary T-cell lymphoma of the brain in a patient at advanced stage of acquired
immunodeficiency syndrome.
AB - OBJECTIVE: To present, to our knowledge, the first case of primary central
nervous system T-cell lymphoma in the setting of acquired immunodeficiency
syndrome. Design.Clinical, radiological, laboratory, and pathological data from a
young patient at advanced stage of acquired immunodeficiency syndrome were
studied. RESULTS: A 38-year-old white man with stage CIII human immunodeficiency
virus infection presented with headaches. Cerebrospinal fluid culture was
positive for mycobacterium. He had facial herpes simplex virus and disseminated
cytomegalovirus infections. Magnetic resonance imaging of the brain showed
multiple areas of patchy or ring-shaped contrast enhancement in the
periventricular zone of the right frontoparietal region. Stereotactic brain
biopsy showed perivascular CD3 (pan T-cell marker)-positive lymphocytic
infiltrates with partial necrosis extending into the neuropil. Not a single cell
was labeled with L26, a B-cell marker. Negative and positive controls were
appropriate. Special stains for cytomegalovirus, herpes simplex virus, Epstein
Barr virus, acid-fast bacilli, and fungi were negative. Gene rearrangement
studies showed rearranged Tgamma and Tbeta bands. Polymerase chain reaction with
a primer specific for Epstein-Barr virus genome-encoding nuclear antigen 1 region
was positive. Human T-cell leukemia/lymphoma virus I work-up was negative. The
patient was treated for mycobacteria. Four months later, he presented with a
paravertebral neck mass. Needle biopsy showed a T-cell lymphoma with morphology
similar to that in the brain. CONCLUSIONS: To our knowledge, this case represents
the first example of T-cell lymphoma of the brain in a patient with advanced
stage of acquired immunodeficiency syndrome. Epstein-Barr virus may play a role
in T-cell lymphomagenesis. The other unique finding is the complete absence of B
cells in a central nervous system lesion. The underlying mechanism eradicating
the B cells is unknown.
PMID- 9648907
TI - Perineurioma with ossification: a case report with immunohistochemical and
ultrastructural studies.
AB - We present the case of a peripheral nerve sheath tumor arising from the sciatic
nerve in the thigh of a 42-year-old woman. Histologically, the tumor was composed
of fascicles of spindle cells with extremely attenuated cytoplasmic processes.
Regions of the tumor were heavily mineralized and fibrotic. The tumor was
epithelial membrane antigen-positive and S100-negative. Staining for Leu-7 was
positive in a patchy distribution. Type IV collagen was present between cells,
and CD34 was negative in the tumor cells. Ultrastructural features included
elongate cellular processes surrounded by discontinuous basal lamina and
collagen. The features of the tumor therefore meet criteria for perineurioma.
This rare tumor is found most often in the extremities in middle-aged woman. To
our knowledge, the presence of bone formation in a perineurioma has not been
described previously. The differential diagnosis includes other peripheral nerve
sheath tumors, low-grade fibrous tumors, and synovial (monophasic) tumors.
Evidence provided by electron microscopy and immunohistochemistry supports the
diagnosis and classification of this unusual nerve sheath tumor as perineurioma
with ossification. These findings expand our knowledge and criteria for
classifying peripheral nerve sheath tumors.
PMID- 9648908
TI - Recurrence of unicystic ameloblastoma: a case report and review of the
literature.
AB - Unicystic ameloblastoma is believed to be less aggressive and responds more
favorably to conservative surgery than the solid or multicystic ameloblastomas.
We report a case of unicystic ameloblastoma that was initially treated by
marsupialization and later by enucleation under suspicion of a dentigerous cyst.
The neoplastic nature of the lesion became evident only when the enucleated
material was available for histologic examination. Apart from an
ameloblastomatous epithelial lining and luminal tumor nodules, the cystic tumor
contained numerous tumor islands within its fibrous capsule. The lesion recurred
8 years after the enucleation. This case supports the view that the presence of
tumor islands in the fibrous capsule may indicate a high risk of recurrence for
unicystic ameloblastomas. Relevant diagnostic problems and choice of treatment
are presented along with a review of the literature.
PMID- 9648909
TI - Rhabdomyosarcoma mimicking acute leukemia in an adult: report of a case with
histologic, flow cytometric, cytogenetic, immunohistochemical, and
ultrastructural studies.
AB - A case of a 25-year-old man who presented with low back, knee, and hip pain with
bruising, leukocytosis, and thrombocytopenia is reported. Histopathologic and
flow cytometric studies revealed a malignant neoplasm, which was thought to be
consistent with an unusual type of acute leukemia. Subsequent immunohistochemical
studies revealed diffuse bone marrow involvement by rhabdomyosarcoma,
demonstrated by positivity for desmin and muscle-specific actin. In addition, the
diagnosis of metastatic rhabdomyosarcoma was confirmed with cytogenetic and
ultrastructural studies. The incidence of rhabdomyosarcoma, a disease usually
seen in childhood, presenting with extensive bone marrow involvement and
mimicking acute leukemia in an adult is extremely rare. This case highlights the
need to consider rhabdomyosarcoma in the differential diagnosis in patients who
present with a leukemic picture and atypical blasts that lack the usual
hematopoietic markers.
PMID- 9648910
TI - Virally activated Ras cooperates with integrin to induce tubulogenesis in
sinusoidal endothelial cell lines.
AB - Four cell lines, named nonparenchymal 11 (NP11), NP26, NP31, and NP32, were
established from sinusoidal endothelial cells (SECs) of rat liver. They still
retained expression of receptors for vascular endothelial growth factor (VEGF),
Fit-1, and kinase domain-containing receptor (KDR). NP31 and NP32 turned out to
be incapable of tubulogenesis in basement membrane matrix (Matrigel), which
belongs to endothelial properties, as shown by SECs in primary culture.
Expression of temperature-sensitive, virally activated Ras (ts-v-Ras) restored
tubulogenic behaviors back to NP31 only at permissive temperature. Matrigel
induced long-lasting tyrosine phosphorylation of Shc, with recruitment of Grb-2
and microtubule-associated protein kinase (MAPK) activation in both parental NP31
and NP31 transformed by ts-v-Ras, which was blocked by anti-beta1 integrin
antibody. Tubulogenesis was inhibited by adenovirus-mediated expression of
dominant-negative Ras in human umbilical vein endothelial cells (HUVECs). PD
098059, a selective inhibitor of MAPK kinase (MEK), nearly perfectly blocked
tubulogenesis by ts-v-Ras-expressing NP31 cells at permissive temperature.
Furthermore, the botulinum C3 toxin, an inhibitor for Rho, caused fragmentation
of branching cords in networks formed by NP31 that expressed ts-v-Ras at
permissive temperature. These data suggest that the integrin-mediated Ras signals
may be necessary but are not sufficient for tubulogenesis and that an artificial
expression of v-Ras might substitute for the second signal required in this
system.
PMID- 9648911
TI - Induction of Ets-1 in endothelial cells during reendothelialization after
denuding injury.
AB - Ets-1, a transcription factor, is induced in endothelial cells (ECs) during
angiogenesis. Here, we investigated the expression of Ets-1 during
reendothelialization. When a confluent monolayer of human umbilical vein
endothelial cell line, ECV304, was denuded, ECV304 at the wound edge expressed
Ets-1. An immunohistochemical analysis revealed that Ets-1 accumulated in
migrating cells at the wound edge and returned to basal level when
reendothelialization was accomplished. This induction of Ets-1 could be
reproduced in in vivo denudation of rat aortic endothelium by a balloon catheter.
The induction of Ets-1 in ECs after denudation was regulated transcriptionally,
and humeral factors released from injured ECs might not be responsible. Mitogen
activated protein kinase (MAPK) activities were investigated to explore the
mechanism of this induction. Although extracellular signal-regulated protein
kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1 (JNK1), and p38 were activated
after denudation, the activation of ERK1 and p38 was more rapid and prominent.
PD98059, a specific MAPK/ERK kinase (MEK) 1 inhibitor, did not affect the
induction of ets-1 mRNA, whereas SB203580, a specific p38 inhibitor, almost
completely abrogated its induction. These results indicate that Ets-1 is induced
in ECs after denudation through activation of p38. This induction of Ets-1 may be
relevant for reendothelialization by regulating the expression of certain genes.
PMID- 9648912
TI - Staurosporine-induced versus spontaneous squamous metaplasia in pre- and
postmenopausal breast tissue.
AB - Breast cancers from pre- vs. postmenopausal women display unique characteristics
that may be related to differences in epithelial differentiation between these
two populations. In addition to lobular development, lactational changes, and
involution, breast epithelium can undergo metaplastic alterations, often in
association with carcinoma. Because protein kinase C (PKC) regulates
differentiation and proliferation in many cell types, we asked whether modulation
of PKC activity could define biochemical differences in breast epithelium from
pre- vs. postmenopausal women. Organ cultures of normal human breast were treated
with PKC agonists and antagonists. Epithelial differentiation was evaluated based
on morphologic criteria and the expression of cell-type specific proteins.
Staurosporine, a nonspecific but extremely potent inhibitor of PKC, induced
squamous metaplasia in eight of eight cases within 2 weeks of treatment. Other
inhibitors of PKC, such as calphostin C and tamoxifen, had no effect on
epithelial differentiation. Long-term treatment with phorbol esters also did not
induce squamous metaplasia. However, stimulation of cAMP levels by forskolin and
isobutyl-methyl-xanthene (IMX) rapidly induced squamous metaplasia, as has been
previously reported. Surprisingly, squamous metaplasia occurred in 10 of 12
cultures derived from postmenopausal women in the absence of exogenous agents.
Untreated cultures derived from premenopausal women never developed this type of
epithelium (0 of 11). Therefore, breast epithelium from pre- and postmenopausal
women responded differently to in vitro culture. Forskolin/IMX or staurosporine
can reproduce these conditions, acting independent of menopausal status. Because
staurosporine's action was unique among PKC inhibitors, staurosporine may induce
squamous metaplasia of breast epithelium by a PKC-independent mechanism.
PMID- 9648913
TI - Epidermal growth factor (EGF)- and scatter factor/hepatocyte growth factor
(SF/HGF)- mediated keratinocyte migration is coincident with induction of matrix
metalloproteinase (MMP)-9.
AB - Receptor tyrosine kinases are key regulators of cellular function including cell
growth, differentiation, migration, and morphogenesis. Disruptions of receptor
tyrosine kinase signaling pathways are often associated with changes in cellular
proliferative capacity and tumorigenesis. Both receptor-specific and cell type
specific factors may contribute to the ultimate cellular responses observed after
receptor activation. In this regard, we find that both normal keratinocytes and
their tumorigenic counterparts display differential responses to activation of
receptor tyrosine kinases. Multiple ligands were mitogenic for keratinocytes, but
only epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha),
and scatter factor/hepatocyte growth factor (SF/HGF) promoted cell motility as
assessed by colony dispersion (scattering) and in vitro reepithelialization.
Interestingly, growth factor specificity for motility coincided with ligand
mediated cell invasion through a reconstituted basement membrane and induction of
the 92-kDa metalloproteinase (MMP-9) activity as determined by gelatin zymogram
analysis. Inhibitors of MMP activity or addition of an MMP-9 neutralizing
antibody resulted in the loss of growth factor-induced colony dispersion,
suggesting a functional role for MMP-9 induction during this response. Coordinate
regulation of MMP-9 induction and the migratory response are likely to contribute
to the enhanced invasive potential observed in response to EGF and SF/HGF. Our
findings suggest that alternate receptor-mediated signaling pathways leading to
differences in gene expression may be involved in complex cellular responses such
as colony dispersion or invasion.
PMID- 9648914
TI - Selective modulation of MAP kinase in embryonic palate cells.
AB - Murine embryonic palate mesenchyme (MEPM) cells are responsive to a number of
endogenous factors found in the local embryonic tissue environment. Recently, it
was shown that activation of the cyclic AMP (cAMP) or the transforming growth
factor beta (TGFbeta) signal transduction pathways modulates the proliferative
response of MEPM cells to epidermal growth factor (EGF). Since the mitogen
activated protein kinase (MAPK) cascade is a signal transduction pathway that
mediates cellular responsiveness to EGF, we examined the possibility that several
signaling pathways which abrogate EGF-stimulated proliferation do so via the
p42/p44 MAPK signaling pathway. We demonstrate that EGF stimulates MAPK
phosphorylation and activity in MEPM cells maximally at 5 minutes. Tyrosine
phosphorylation and activation of MAPK was unaffected by treatment of MEPM cells
with TGFbeta or cholera toxin. Similarly, TGFbeta altered neither EGF-induced
MAPK tyrosine phosphorylation nor activity. However, the calcium ionophore,
A23187, significantly increased MAPK phosphorylation which was further increased
in the presence of EGF, although calcium mobilization reduced EGF-induced
proliferation. Despite the increase in phosphorylation, we could not demonstrate
induction of MAPK activity by A23187. Like EGF, phorbol ester, under conditions
which activate PKC isozymes in MEPM cells, increased MAPK phosphorylation and
activity but was also growth inhibitory to MEPM cells. The MEK inhibitor,
PD098059, only partially abrogated EGF-induced phosphorylation. Likewise,
depletion of PKC isozymes partially abrogated EGF-induced MAPK phosphorylation.
Inhibition of both MEK and PKC isozymes resulted in a marked decrease in MAPK
activity, confirming that EGF uses multiple pathways to stimulate MAPK activity.
These data indicate that the MAPK cascade does not mediate signal transduction of
several agents that inhibit growth in MEPM cells, and that there is a
dissociation of the proliferative response and MAP kinase activation.
Furthermore, other signaling pathways known to play significant roles in
differentiation of palatal tissue converge with the MAPK cascade and may use this
pathway in the regulation of alternative cellular processes.
PMID- 9648915
TI - CD77-dependent retrograde transport of CD19 to the nuclear membrane: functional
relationship between CD77 and CD19 during germinal center B-cell apoptosis.
AB - A region of the N-terminal extracellular domain of the B-cell restricted cell
differentiation antigen, CD19, has high amino acid sequence similarity to the
receptor binding subunit B of verotoxin 1 (VT), an Escherichia coli elaborated
cytotoxin, which specifically binds to the cell surface glycolipid,
globotriaosylceramide, also known as the germinal center (GC) B-cell
differentiation antigen, CD77. We have previously provided evidence of the
association of CD19 and CD77 on the cell surface and in CD19-mediated homotypic
adhesion of the Daudi Burkitt Lymphoma cell line, one normal counterpart of which
is a subset of GC B cells. Evidence for the role of CD77 in CD19-induced
apoptosis is now presented. Initial cell surface distribution, antibody-induced
redistribution, internalization, and intracellular routing of CD19 were studied
by confocal microscopy, IF, and postembedding IEM in CD77+ve and CD77-ve cells to
investigate the possible role of CD77 in CD19 internalization and signaling.
Daudi Burkitt's lymphoma cells were used as CD77+ve cells and as CD77-ve cells,
Daudi mutant VT500 cells, and Daudi cells treated with PPMP, an inhibitor of CD77
synthesis, were used. Antibody ligated CD19 surface redistribution,
internalization, and subcellular distribution of internalized CD19 was found to
be different in CD77+ve and CD77-ve cells. A delay in internalization of antibody
CD19 complex was observed in CD77-ve cells. Internalized CD19 was targeted to the
nuclear envelope in CD77+ve cells in a manner similar to that reported for VT,
but not in CD77-ve cells. Internalization of CD77 by ligation with verotoxin
prevented the internalization of ligated CD19. Induction of apoptosis following
crosslinking of cell surface CD19 was greater in CD77+ve cells than in CD77-ve
cells. The nuclear targeting of internalized CD19 and induction of apoptosis
following CD19 crosslinking only in CD77+ve cells indicates a role for CD77
dependent CD19 retrograde transport from the B cell surface via the ER to the
nuclear envelope in CD19-mediated signal transduction for apoptosis.
PMID- 9648916
TI - Cell shape-dependent pathway of plasminogen activator inhibitor type-1 gene
expression requires cytoskeletal reorganization.
AB - Synthesis of plasminogen activator inhibitor type-1 (PAI-1), a major
physiological modulator of plasmin generation, is regulated by growth factors and
changes in cell shape. To evaluate the specific relationship between PAI-1 gene
expression and cytoarchitecture, serum-free cultures of quiescent rat kidney
(NRK) cells were exposed to cytochalasin D (CD) at concentrations that disrupt
microfilament structure. Treatment with 1-10 microM CD resulted in an increased
1) incidence of rounded cells, 2) relative PAI-1 mRNA content, and 3) fraction of
PAI-1 protein-expressing cells. Abrupt increases in each response were evident at
a final concentration of 5 microM CD. Maximal levels of induced PAI-1 transcripts
(18-fold that of control) occurred 4 hours post-CD addition and declined
thereafter but remained elevated (by at least tenfold) for 24 hours. Assessment
of the metabolic requirements for CD-induced PAI-1 expression by using the
protein synthesis inhibitors puromycin and cycloheximide indicated that PAI-1
transcripts were regulated in a complex manner in response to CD. The predominant
mode of induction reflected secondary (protein synthesis-dependent) metabolic
processes, although a minor, albeit significant, primary (protein synthesis
independent) pathway was also evident. PAI-1 mRNA levels in NRK cells maintained
in serum- and CD-free agarose suspension culture were low or undetectable.
Relative abundance of PAI-1 transcripts in suspended cells cultured in the
presence of CD, however, closely approximated that of plastic-adherent, CD
treated cells (13-fold over control). NRK cells in suspension culture with or
without CD were morphologically identical, remaining spherical and unattached. It
appears, therefore, that cell rounding alone is not a sufficient stimulus to
induce PAI-1 expression in quiescent NRK cells and that perturbation of the actin
skeleton as a consequence of CD treatment is a critical event in the inductive
response. A protein tyrosine kinase is likely involved in the CD-mediated signal
transduction cascade, since induced PAI-1 expression can be down-regulated by
genistein and herbimycin A but not by calphostin C or tyrphostin B46.
PMID- 9648917
TI - Dedifferentiated chondrocytes cultured in alginate beads: restoration of the
differentiated phenotype and of the metabolic responses to interleukin-1beta.
AB - Chondrocytes cultivated in monolayer rapidly divide and lose their morphological
and biochemical characteristics, whereas they maintain their phenotype for long
periods of time when they are cultivated in alginate beads. Because cartilage has
a low cellularity and is difficult to obtain in large quantities, the number of
available cells often becomes a limiting factor in studies of chondrocyte
biology. Therefore, we explored the possibility of restoring the differentiated
properties of chondrocytes by cultivating them in alginate beads after two
multiplication passages in monolayer. This resulted in the reexpression of the
two main markers of differentiated chondrocytes: Aggrecan and type II collagen
gene expression was strongly reinduced from day 4 after alginate inclusion and
paralleled protein expression. However, 2 weeks were necessary for total
suppression of type I and III collagen synthesis, indicators of a modulated
phenotype. Interleukin-1beta, a cytokine that is present in the synovial fluid of
rheumatoid arthritis patients, induces many metabolic changes on the chondrocyte
biology. Compared with cells in primary culture, the production of nitric oxide
and 92-kDa gelatinase in response to interleukin-1beta was impaired in cells at
passage 2 in monolayer but was fully recovered after their culture in alginate
beads for 2 weeks. This suggests that the effects of interleukin-1beta on
cartilage depend on the differentiation state of chondrocytes. This makes the
culture in alginate beads a relevant model for the study of chondrocyte biology
in the presence of interleukin-1beta and other mediators of cartilage destruction
in rheumatoid arthritis and osteoarthrosis.
PMID- 9648918
TI - Characterization of gene-specific DNA repair by primary cultures of rat
hepatocytes.
AB - At present, almost all the information on gene-specific DNA repair in mammals
comes from studies with transformed cell lines and proliferating primary cells
obtained from rodents and humans. In the present study, we measured the repair of
specific DNA regions in primary cultures of nondividing rat hepatocytes
(parenchymal cells). DNA damage was induced by irradiating the primary cultures
of hepatocytes with ultraviolet (UV) light, and the presence of cyclobutane
pyrimidine dimers (CPDs) was measured by using T4 endonuclease V in the
following: a 21-kb BamHI fragment containing the albumin gene, a 14-kb BamHI
fragment containing the H-ras gene, and the genome overall. The frequency of CPDs
in the two BamHI fragments and the genome overall were similar and ranged from
0.5 to 1.3 CPDs per 10 kb for UV doses of 5-30 J/m2. However, the removal of CPDs
from the DNA fragment containing the albumin gene was significantly higher than
from that of the genome overall and the DNA fragment containing the H-ras gene.
Within 24 hr, approximately 67% of the CPDs was removed from the DNA fragment
containing the albumin gene versus less than 40% for the genome overall and the
DNA fragment containing the H-ras gene. The lower repair observed for the 14-kb
fragment containing the H-ras gene is probably indicative of repair of the
nontranscribed region of this fragment because the H-ras gene makes up only 2.4
kb of the 14-kb fragment. Primary cultures of hepatocytes removed CPDs from the
transcribed strand of albumin fragment more efficiently than from the
nontranscribed strand; however, no differences were observed in the repair of the
two strands of the fragment containing the H-ras gene. These results demonstrate
that primary cultures of nondividing rat hepatocytes show differential repair of
UV-induced DNA damage that is comparable to what has been reported for
transformed, proliferating mammalian cell lines.
PMID- 9648919
TI - Retroviral-mediated gene transfer of CSF-1 into op/op stromal cells to correct
defective in vitro osteoclastogenesis.
AB - Colony-stimulating factor-1 (CSF-1) released by stromal cells in the bone
microenvironment is essential for the proliferation of osteoclast progenitors. In
op/op mutant mice, a thymidine insertion in the coding sequence of the CSF-1 gene
results in CSF-1 deficiency that in turn leads to decreased osteoclast production
and osteopetrosis. Because the osteopetrotic defect is due to the failure of
stromal cells to produce CSF-1, we determined if retroviral-mediated gene
transfer of the wild-type CSF-1 cDNA into op/op stromal cells would restore their
ability to support osteoclast formation in vitro. A retroviral vector, L-CSF-1
SN, was constructed by inserting 1,867 bp of the wild-type CSF-1 cDNA into pLXSN.
After transduction with L-CSF-1-SN or LXSN constructs, a stable PA31 7 packaging
cell line that produced a high viral titre was isolated. Viral supernatant from
this line was used to infect op/op bone marrow stromal cells. Stable L-CSF-1-SN
op/op stromal clones overexpressed CSF-1 mRNA and released CSF-1 into conditioned
medium, compared with no CSF-1 released by LXSN op/op stroma. The amount of CSF-1
produced by two clones was similar to the physiologic level released by normal
littermate stroma. Southern blot analysis confirmed the presence of intact
proviral sequences in transduced cells. In coculture assays, L-CSF-1-SN, but not
LXSN, op/op stromal cells supported the formation of TRAP-positive multinucleated
cells in the absence of exogenous CSF-1. These findings indicate that genetically
engineered stromal cells may be used to improve defective osteoclastogenesis and
suggest that targeting stromal cells to bone is a potentially useful therapeutic
modality for treating bone disorders.
PMID- 9648920
TI - Platelet-derived growth factor-induced disruption of gap junctional communication
and phosphorylation of connexin43 involves protein kinase C and mitogen-activated
protein kinase.
AB - Previously we showed a rapid and transient inhibition of gap junctional
communication (GJC) by platelet-derived growth factor (PDGF) in T51B rat liver
epithelial cells expressing wild-type platelet-derived growth factor beta
receptors (PDGFrbeta). This action of PDGF correlated with the
hyperphosphorylation of the gap junction protein connexin43 (Cx43) and required
PDGFrbeta tyrosine kinase activity, suggesting the participation of protein
kinases and phosphatases many of which are activated by PDGF treatment. In the
present study, two such kinases, namely protein kinase C (PKC) and mitogen
activated protein kinase (MAPK), are investigated for their possible involvement
in PDGF-induced closure of junctional channels and Cx43-phosphorylation. Down
regulation of PKC-isoforms by 12-O-tetradecanoylphorbol-13-acetate or
pretreatment with the PKC inhibitor calphostin C, completely blocked PDGF action
on GJC and Cx43. Activation of MAPK correlated with PDGF-induced Cx43
phosphorylation, and prevention of MAPK activation by PD98059 eliminated the PDGF
effects. Interestingly, elimination of GJC recovery by cycloheximide was
associated with a sustained activated-MAPK level. Based on these results we
postulate that the activation of PKC and MAPK are required in PDGF-mediated Cx43
phosphorylation and junctional closure.
PMID- 9648921
TI - Eicosapentaenoic acid attenuates vascular endothelial growth factor-induced
proliferation via inhibiting Flk-1 receptor expression in bovine carotid artery
endothelial cells.
AB - Eicosapentaenoic acid (EPA; 20:5, n-3) can restrain tumor growth and metastasis
in vivo; however, the mechanism of its antitumor effect is still not fully
understood. Angiogenesis is a crucial process for tumor growth and metastasis and
inhibition of tumor angiogenesis can suppress tumor growth and metastasis in
vivo. Vascular endothelial growth factor (VEGF) is an important angiogenic
factor. In this study, we investigated the mechanisms of the inhibitory effect of
EPA on VEGF-induced proliferation of bovine carotid artery endothelial (BAE)
cells. BAE cells, treated with 0-5 microg/ml EPA for 48 h, displayed a dose
dependent suppression to VEGF (0.2 nM)-induced proliferation. Similar inhibitory
effect was not found in BAE cells treated with arachidonic acid (AA; 20:4, n-6),
or docasahexaenoic acid (DHA; 22:5, n-3). In contrast to its effect on VEGF
induced proliferation, EPA had no inhibition to basic fibroblast growth factor
(bFGF, 0.2 nM)-induced proliferation in BAE cells. Both VEGF and bFGF activated
mitogen-activated protein (MAP) kinase in BAE cells; however, EPA selectively
inhibited VEGF-induced, but not bFGF-induced activation of MAP kinase. Flk-1
expression was inhibited dose-dependently in EPA-treated cells, whereas Flt-1
expression was increased in EPA treated cells. This in vitro inhibitory effect by
EPA on Flk-1 receptor expression provides indirect evidence that one of the
mechanisms of EPA for antitumor action in vivo maybe related to its
antiangiogenic action.
PMID- 9648922
TI - In vivo overexpression of Core2 N-acetylglucosaminyltransferase prevents
repopulation of the bone marrow with colony forming cells but fails to affect
normal T cell development.
AB - UDP-GlcNAc:Galbet1 --> 3GalNAc-R beta1 --> 6N-acetylglucosaminyltransferase
(Core2 N-acetyl-glucosaminyltransferase, C2GnT; EC 2.4.1.102) forms beta1 --> 6N
acetyl-glucosaminyl linkages in O-glycoproteins and creates branches for the
addition of N-acetyl-lactosamine antennae. Changes in C2GnT activity have been
associated with immune disorders, malignancies, and T-cell ontogeny. In this
study, we used SCID (severe combined immune deficiency) mice to determine the
effects of C2GnT overexpression on hemopoiesis, and in particular, on thymocyte
development. BALB/c bone marrow cells transfected with C2GnT using the retroviral
murine stem cell vector were used to repopulate SCID mice. Mice were analysed 3
weeks to 3 months after bone marrow transfer. Elevated levels of C2GnT activity
in bone marrow, spleen, and thymus from mice repopulated with C2GnT transfected
bone marrow cells indicated that C2GnT was overexpressed in recipient mice. In
C2GnT repopulated mice, up to 50% of T cells showed an increase in CD43 130-kDa
expression, compared with T cells from control animals, indicative of an elevated
C2GnT activity in these cells. Furthermore, T-cell subset numbers appeared to be
normal, suggesting that C2GnT overexpression did not alter T-cell ontogeny.
Interestingly, C2GnT overexpression negatively affected the repopulation of
myeloid cells. Only insignificant numbers of interleukin-3/granulocyte-macrophage
colony stimulating factor (IL-3/GM-CSF) responsive bone marrow cells were found
to be retrovirally transfected in C2GnT repopulated mice, whereas up to 50% of IL
3/GM-CSF responsive bone marrow cells were found to be retrovirally transfected
in corresponding controls. These data indicate that in vivo overexpression of
C2GnT negatively interferes with the myeloid differentiation pathway but does not
affect T-cell development.
PMID- 9648923
TI - Amino acid depletion modulates vascular endothelial growth factor production
during the life span of human vascular smooth muscle cells.
AB - The role of nutrient supply in the replicative capacity and secretory phenotype
of cultured human diploid cells is unclear. We examined the relationship between
amino acid privation, the secretion of vascular endothelial growth factor (VEGF)
and growth phenotype of vascular smooth muscle cells (VSMC), and endothelial
cells. Cultures of VSMCs, but not endothelial cells, were growth inhibited by
exposure to medium that was 75% deficient in leucine, methionine, arginine, and
cysteine over two passages. Exposed VSMC cultures exhibited an increased
vulnerability to apoptosis. The maximal cumulative population doubling of the
exposed cells was reduced significantly compared with the control cells (25.7 +/-
2.0 doublings vs. 27.9 +/- 2.1 doublings; P < 0.03). Constitutive VEGF production
first became evident in the later passages of the exposed and nonexposed cell
cultures. However, production of VEGF was 17-fold greater in the exposed cultures
at the tenth passage (P < 0.001). The replicative capacity and constitutive
production of VEGF in VSMCs in culture may be programmed by transient privation
of amino acids. These observations are relevant to new concepts concerning the
pathogenesis of vascular disease.
PMID- 9648924
TI - Reaction of mast cell proteases tryptase and chymase with protease activated
receptors (PARs) on keratinocytes and fibroblasts.
AB - Protease activated receptors (PARs) compose a family of G protein signal
transduction receptors activated by proteolysis. In this study, the
susceptibility of PARs expressed on human keratinocytes and dermal fibroblasts to
the human mast cell proteases tryptase and chymase was evaluated. PAR activation
was measured by monitoring cytosolic [Ca2+] in cells loaded with the fluorescent
Ca2+ probe Fura-2. Tryptase produced transient cytosolic Ca2+ mobilization in
keratinocytes, but not in fibroblasts. Ca2+ mobilization in keratinocytes
required enzymatically active tryptase, demonstrated desensitization, and was
blocked by pretreatment of cells with the PAR-2 peptide agonist SLIGKV, trypsin,
or the phospholipase inhibitor U73122. Heparin, a GAG that binds to tryptase,
stabilizing its functional form, also inhibited tryptase-induced Ca2+
mobilization. The maximal response elicited by tryptase was smaller than that
observed upon treatment of keratinocytes with trypsin, a known activator of PAR
2, and keratinocytes made refractory to tryptase by pretreatment with the
protease remained responsive to trypsin. Pretreatment of keratinocytes with
thrombin, an activator of PAR-1 and -3 (thrombin receptors), had no detectable
effect on the tryptase or trypsin responses. These data suggest that in
keratinocytes tryptase may be activating a subpopulation of PAR-2 receptors.
Treatment of keratinocytes or fibroblasts with human chymase did not produce Ca2+
mobilization, nor did it affect Ca2+ mobilization produced by trypsin. However,
chymase pretreatment of fibroblasts rapidly inhibited the ability of these cells
to respond to thrombin. Inhibition was dependent on chymase enzymatic activity
and was not significantly affected by the presence of heparin. This finding is
consistent with studies indicating that PAR-1 may be susceptible to proteases
with chymotrypsin-like specificity. These results suggest that the proteases
tryptase and chymase secreted from mast cells in skin may affect the behavior of
surrounding cells by the hydrolysis of PARs expressed by these cells.
PMID- 9648925
TI - Stretch-induced membrane type matrix metalloproteinase and tissue plasminogen
activator in cardiac fibroblast cells.
AB - In the normal heart, cardiomyocytes are surrounded by extracellular matrix (ECM)
and latent matrix metalloproteinases (MMPs), which are produced primarily by
cardiac fibroblasts. An activator of latent MMPs might be induced by ischemic
conditions or pressure-induced stretching. To test the hypothesis that an
activator of latent MMP is induced in the ischemic heart during transformation of
a compensatory hypertrophic response to a decompensatory failing response in
cardiac fibroblast cells, we stretched the human cardiac fibroblasts at 25
cycles/min in serum-free or 5% serum culture condition. The membrane type (MT)
MMP activity in stretched cells was measured by zymography and immuno-blot
analyses using MT-MMP-2 antibody. The MT-MMP activity was further characterized
by transverse-urea gradient (TUG)-zymography. The results suggested that stretch
induced a membrane MMP in the fibroblasts that was similar to the MT-MMP induced
in ischemic heart. Furthermore, we observed that membrane MMP has distinct
mobility in TUG-zymography. To localize the MT-MMP and tissue plasminogen
activator (tPA) of latent MMPs, the membrane and cytosol were separated by a
method employing a detergent and sedimentation. The MT-MMP and tPA activities of
cytosol and membrane fractions were measured by gelatin- and plasminogen
zymography, respectively. Differential-display mRNA analysis was performed on
control and stretched cells. In situ immuno-labelling was performed to localize
the MT-MMP. The results indicate that induction of MT-MMP occurred in the
membrane fractions. The secretion of tPA was elevated in the stretched cells. The
MT-MMP activity was inhibited by prior incubation with an antibody generated to
membrane MMP. The tPA activity was inhibited by using tPA antibody. These results
suggest that, under stretched conditions, neutral transmembrane matrix
proteinases are induced in the cardiac fibroblasts. This may lead to activation
of adverse ECM remodeling, cardiac dilatation, and failure.
PMID- 9648926
TI - Heregulin-dependent autocrine loop regulates growth of K-ras but not erbB-2
transformed rat thyroid epithelial cells.
AB - The EGF-like family of proteins, such as epidermal growth factor (EGF),
transforming growth factor alpha (TGFalpha), amphiregulin (AR), betacellulin
(BTC), cripto-1 (CR-1), and heregulin (HRG), plays an important role in the
pathogenesis of several human carcinomas as autocrine growth factors.
Differentiation and proliferation of rat thyroid cells in culture (FRTL-5 cells)
are regulated by thyrotropin (TSH); withdrawal of TSH from culture medium
produces growth arrest, whereas its addition to quiescent cells stimulates cell
entry into S phase. Instead, transformed thyroid cell lines as FRTL-5H2 cell
line, overexpressing erbB-2, Kimol cells, transformed by the wild-type K-ras and
A6 clone, transformed by a temperature sensitive K-ras mutant, can grow without
addition of TSH to the culture medium. In order to identify whether EGF-like
growth factors and corresponding receptors (erbB-2, erbB-3, and erbB-4) could be
involved in the autonomous growth of these transformed rat thyroid epithelial
cells, Northern blot for mRNA analysis and Western blot for protein expression
were performed. In contrast to normal control FRTL-5 cells, both K-ras and erbB-2
transformed cells expressed elevated levels of erbB-2 receptor. Moreover, both K
ras transformed cells, Kimol and A6 cells, but no FRTL-5H2 cells, were found able
to express also high levels of erbB-4 receptor and HRG/NDF ligand. Treatment of K
ras transformed thyroid cells with neutralizing antibody against HRG/NDF reduced
by 50% cell proliferation. These data indicate that unlike the erbB-2
overexpressing FRTL-5 cells, in K-ras rat thyroid epithelial cells, the growth
factor heregulin signals through the heterodimer erbB-2/erbB-4 receptors in an
autocrine fashion.
PMID- 9648927
TI - Multivalent cations and ligand affinity of the type 1 insulin-like growth factor
receptor on P2A2-LISN muscle cells.
AB - Mouse P2A2-LISN myoblasts are transfected cells that overexpress the human type 1
insulin-like growth factor (IGF) receptor. Because the type 1 IGF receptor is the
major binding site for both IGF-I and IGF-II, this cell line is an excellent
model to determine the effect of multivalent cations on ligand binding
specifically to this type of receptor. Competitive binding assays were performed
to characterize IGF binding and Scatchard analysis to quantify affinity (Ka).
125I-IGF-I, 125I-IGF-II, and 125I-R3-IGF-I bind only to the type 1 IGF receptor
on these cells. Zn2+ increased binding of the three ligands to the type 1 IGF
receptor by 17 to 35%. Cd2+ significantly increased binding of 125I-IGF-I,
although by only 8%. La3+ and Cr3+ did not effect binding. Au3+ decreased IGF
binding by approximately 56%. Scatchard analysis produced nonlinear concave-down
plots yielding binding constants for high and low affinity sites. Zn2+ increased
the strength of only the high affinity sites. Au3+ decreased the affinity of both
high and low affinity sites. Zn2+ increased binding with a half-maximal effect
between 40 microM and 60 microM. Half-maximal dose of Au3+ was >130 microM. Zinc,
gold, and cadmium bind to similar regions within proteins (a zinc-binding motif)
and only these cations were found to affect receptor binding indicating similar
mechanisms of action. Thus, multivalent cations may alter IGF binding to cell
surface receptors ultimately controlling growth. Physiologically this may be
especially important for the growth promoting effects of Zn2+.
PMID- 9648928
TI - Overexpression of protein kinase C alpha enhances lipopolysaccharide-induced
nitric oxide formation in vascular smooth muscle cells.
AB - Our previous studies showed that lipopolysaccharide (LPS)-induced nitric oxide
(NO) synthesis in cardiovascular tissues is attenuated by protein kinase C (PKC)
inhibitors. In the current study, we identify a specific PKC isotype involved in
the LPS signal transduction pathway that leads to NO formation in rat vascular
smooth muscle cells (VSMC). VSMC were transfected with a mammalian expression
vector containing a full length PKCalpha cDNA insert, and a stable transfectant
overexpressing PKCalpha was obtained as evidenced by increased expression of
PKCalpha mRNA and protein. In response to 100 ng/ml LPS stimulation, the PKCalpha
transfectants showed a 1.8-fold increase in PKC activity at 30 min and a twofold
increase in NO production over 24 hr compared with cells transfected with control
plasmids. The LPS-stimulated increase in NO synthesis in PKCalpha transfectants
was blocked by the specific PKCalpha inhibitor Go 6976. After 6 hr LPS treatment,
PKCalpha-transfected and control cells showed equivalent increases in mRNA and
protein for the inducible NO synthase. NO synthase activity of the cell extracts
assayed in the presence of excess substrate and cofactors was not significantly
different between PKCalpha-transfected and control cells after LPS stimulation.
However, mRNA levels for GTP cyclohydrolase I, a key enzyme in (6R)-tetrahydro-L
biopterin synthesis, and cationic amino acid transporter-2, involved in L
arginine transport, was enhanced in cells overexpressing PKCalpha compared with
control cells. These results suggest that PKCalpha plays an important role in LPS
induced NO formation and that a significant portion of this effect may be by
means of enhanced substrate availability to the inducible nitric oxide synthase
enzyme.
PMID- 9648929
TI - Different signaling pathway between sphingosine-1-phosphate and lysophosphatidic
acid in Xenopus oocytes: functional coupling of the sphingosine-1-phosphate
receptor to PLC-xbeta in Xenopus oocytes.
AB - In Xenopus oocytes, both sphingosine-1-phosphate (S1P) and lysophosphatidic acid
(LPA) activate Ca2+-dependent oscillatory Cl- currents by acting through membrane
bound receptors. External application of 50 microM S1P elicited a long-lasting
oscillatory current that continued over 30 min from the beginning of oscillation,
with 300 nA (n = 11) as a usual maximum peak of current, whereas 1-microM LPA
treatment showed only transiently oscillating but more vigorous current
responses, with 2,800 nA (n = 18) as a maximum peak amplitude. Both phospholipid
induced Ca2+-dependent Cl- currents were observed in the absence of extracellular
Ca2+, were blocked by intracellular injection of the Ca2+ chelator, EGTA, and
could not be elicited by treatment with thapsigargin, an inhibitor of endoplasmic
reticulum (ER) Ca2+ ATPase. Intracellular Ca2+ release appeared to be from
inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store, because Cl- currents
were blocked by heparin injection. Pretreatment with the aminosteroid, U-73122,
an inhibitor of G protein-mediated phospholipase C (PLC) activation, to oocytes
inhibited the current responses evoked both by S1P and LPA. However, when they
were injected with 10 ng of antisense oligonucleotide (AS-ODN) against Xenopus
phospholipase C (PLC-xbeta), oocytes could not respond to S1P application,
whereas they responded normally to LPA, indicating that the S1P signaling pathway
goes through PLC-xbeta, whereas LPA signaling goes through another unknown PLC.
To determine the types of G proteins involved, we introduced AS-ODNs against four
types of G-protein alpha subunits that were identified in Xenopus laevis;
G(q)alpha, G11alpha, G0alpha, and G(i1)alpha. Among AS-ODNs against the G alphas
tested, AS-G(q)alpha and AS-G(i1)alpha to S1P and AS-G(q)alpha and AS-G11alpha to
LPA specifically reduced current responses, respectively, to about 20-30% of
controls. These results demonstrate that LPA and S1P, although they have similar
structural features, release intracellular Ca2+ from the IP3-sensitive pool, use
different components in their signal transduction pathways in Xenopus oocytes.
PMID- 9648930
TI - Expression of transforming growth factor-beta receptor type II and tumorigenicity
in human breast adenocarcinoma MCF-7 cells.
AB - To analyze transforming growth factor-beta (TGF-beta) response during MCF-7 cell
progression, early passage (MCF-7E, < 200 passage) and late passage (MCF-7L, >
500 passage) cells were compared. MCF-7E cells showed an IC50 of approximately 10
ng/ml of TGF-beta1, whereas MCF-7L cells were insensitive. MCF-7E cells contained
approximately threefold higher levels of TGF-beta receptor type II (TbetaRII)
mRNA than MCF-7L, but their TbetaRI levels were similar. MCF-7E parental cells
showed higher TbetaRII promoter activity than MCF-7L cells, which could be
attributed to changes in Sp1 nuclear protein levels. Receptor cross-linking
studies indicated that the cell surface receptor levels parallel mRNA levels in
both cell lines. Limiting dilution clones of MCF-7E cells were established to
determine the heterogeneity of TbetaRII expression in this cell line, and they
showed varying degrees of TbetaRII expression. Fibronectin was induced at higher
levels in cells expressing higher TbetaRII levels. All three TGF-beta isoforms
were detected in limiting dilution clones and parental cells, but TGF-beta1 was
more abundant relative to TGF-beta2 or 3, and no correlation between TGF-beta
isoform profile with TGF-beta sensitivity was found. MCF-7L cells were
tumorigenic and formed xenografts rapidly and progressively, whereas MCF-7E
parental and limiting dilution clonal cells showed transient tumor formation
followed by regression. These results indicate that decreased TbetaRII
transcription in breast cancer cells leads to a loss of TbetaRII expression,
resulting in cellular resistance to TGF-beta which contributes to escape from
negative growth regulation and tumor progression.
PMID- 9648931
TI - 17beta-estradiol regulation of protein kinase C activity in chondrocytes is sex
dependent and involves nongenomic mechanisms.
AB - 17Beta-estradiol (E2) regulates growth plate chondrocyte differentiation in both
a sex- and cell maturation-dependent manner, and the sex-specific effects of E2
appear to be mediated in part by membrane events. In this study, we examined
whether E2 regulates protein kinase C (PKC) in a cell-maturation and sex-specific
manner and whether E2 uses a nongenomic mechanism in regulating this enzyme. In
addition, we determined if PKC mediates the E2-dependent stimulation of alkaline
phosphatase activity seen in chondrocytes. Confluent, fourth passage resting zone
(RC) and growth zone (GC) chondrocytes from male and female rat costochondral
cartilage were treated with 10(-10) to 10(-7) M E2. E2 caused a dose-dependent
increase in PKC in RC and GC cells from female rats. Peak stimulation was at 90
min. Increased PKC was evident by 3 min in both RC and GC and was still evident
in RC cells at 720 min, but in GC cells activity returned to baseline by 270 min.
Actinomycin D had no effect at 9, 90, 270, or 720 min, but there was a small
decrease in E2-stimulated PKC in RC treated with cycloheximide at 90 and 270 min
and in GC treated for 90 min. E2 increased cytosolic and membrane PKC at 9 min
and by 90 min promoted translocation of PKC activity from the cytosol to the
membranous compartment of female RC cells. Antibodies specific for the alpha,
beta, delta, epsilon, and zeta isoforms of PKC revealed that PKCalpha in female
GC and RC cells is activated by E2. There was a small, but statistically
significant, increase in PKC in male RC cells in response to E2, but it was not
dose-dependent, and no effect of E2 was noted in male GC cells. 17Alpha
estradiol, an inactive isomer of E2, did not affect PKC specific activity in RC
or GC cells from either female or male rats. Chelerythrine, a specific inhibitor
of PKC, inhibited E2-dependent alkaline phosphatase activity, indicating that E2
mediates its rapid effects on alkaline phosphatase via PKC.
PMID- 9648932
TI - Hypothesis: ligand/receptor-assisted nuclear translocation of STATs.
AB - The STAT transcription factors are mediators of signal transduction of a variety
of factors, including interferons (IFNs), interleukins, growth factors, and
peptide hormones. Subsequent to activation, STATs are translocated to the nucleus
apparently through the well-described importin/Ran system, where they activate
target genes. Molecules utilizing this nuclear import system require specific
nuclear localization sequences (NLSs). Paradoxically, such NLSs are not
identifiable on STATs, thus raising the question of how they are imported into
the nucleus. Of considerable interest is the observation that ligands and/or
receptors that signal through STATs contain putative NLSs and, where examined,
either ligand or receptor undergoes nuclear translocation. We hypothesize that
ligands and/or their receptors serve as vehicles for the nuclear translocation of
STATs, and that they may be directly involved in signal transduction. Using
IFNgamma as a model system, we provide a possible mechanism for how this direct
role is fulfilled. A functional NLS has been identified in a C-terminal domain of
IFNgamma. This domain and the NLS contained within are crucial for the biological
properties of IFNgamma in that a peptide encompassing this domain is sufficient
to induce an antiviral state. Further, this domain binds specifically to a
membrane-proximal region internal cytoplasmic domain of the alpha subunit of the
receptor complex in a region that is directly involved in the recruitment and
activation of the JAK/STAT pathway. We suggest that this novel mode of receptor
recognition and activation may be a driving force for nuclear translocation of
molecules like STATs that are associated with the ligand-receptor complex.
PMID- 9648933
TI - Endogenous sodium pump inhibitors and blood pressure regulation: an update on
recent progress.
AB - Rapid progress has occurred recently in understanding the origin, chemistry,
synthesis, control, and actions of endogenous materials that may be ligands for
the cardiac glycoside binding site on the mammalian sodium pump (Na,K-ATPase).
The present paper reviews this progress and examines in detail the evidence
supporting ouabain-like and bufodienolide-like compounds as functioning in
endogenous control of sodium pump activity, renal sodium excretion, blood
pressure, and cardiovascular contractility. Other novel compounds identified in
this search as potentially influencing natriuresis and blood pressure are also
discussed.
PMID- 9648934
TI - Pathophysiological effects of nicotine on the pancreas.
PMID- 9648935
TI - The actions of exogenous dehydroepiandrosterone in experimental animals and
humans.
AB - Dehydroepiandrosterone (DHEA) is the major adrenal steroid of young adults;
however, its physiologic functions, if any, are not known. The purpose of this
review is to evaluate the current literature in which DHEA was administered to
either humans or experimental animals to discern what these functions might be.
Reports are divided into five areas: neurologic, immunologic, cardiovascular,
oncologic, and metabolic. Particular attention is paid to the dosage and route of
administration. This type of analysis shows that at the lowest doses, DHEA has
effects on neurologic and immunologic tissues, suggesting that these two sites
may be physiologic targets. DHEA also affects cardiologic and metabolic functions
as well as tumor growth, but such actions require higher doses and may reflect
'pharmacologic' activities. It is proposed that DHEA's pattern of activity
represents a new class of steroid hormones, the "Regnantoids." Further progress
in the endocrinology of this family of steroids may only come when synthetic,
long-acting analogs of DHEA are available for in vitro studies to allow
correlations between hormone action and receptor binding.
PMID- 9648936
TI - Ion channels in vascular smooth muscle: alterations in essential hypertension.
AB - Essential hypertension is characterized by a near normal cardiac output but an
increase in total peripheral resistance. In turn, total peripheral resistance is
controlled directly by the diameter of the small arteries and arterioles like
those in the kidney. The dynamic regulation of renal vessel diameter is governed
by the contractile state of the vascular smooth muscle cells that line the vessel
walls. This review addresses the role of a number of different ion channels to
initiate and maintain the contractile state of the vascular smooth muscle cells
in hypertension and the potential prevention of hypertension through gene
therapy. These specific channels include Ca2+, K(Ca), Kv, and Cl- channels. In
hypertension, it has been reported that increased activity of Ca2+ channels and
decreased activity of Kv channels are responsible for the increased contractile
tone and resting membrane potential observed in dissociated vascular smooth
muscle cells from the spontaneously hypertensive rat. In contrast, increased
activity of K(Ca) channels in vascular smooth muscle cells of the SHR has been
hypothesized to dampen or brake the activity of Ca2+ and Kv channels. Finally,
recent evidence suggests that introducing angiotensin II type-1 receptor
antisense into prehypertensive rat pups prevents the onset of pathophysiological
alterations observed in hypertension including K+ channel alterations. These
results suggest that gene therapy may be a useful pharmacological and
physiological tool to combat hypertension.
PMID- 9648937
TI - Attenuation of gonadotropin-releasing hormone reflex to coitus by alpha1
adrenergic receptor blockade in the rabbit.
AB - The coitally induced gonadotropin-releasing hormone (GnRH)/luteinizing hormone
(LH) surge in the rabbit is preceded by an enhanced secretion of hypothalamic
norepinephrine (NE). To investigate if adrenergic receptors are essential for the
GnRH/LH surge, we administered a specific alpha1 receptor blocker, prazosin, into
either the arcuate nucleus-median eminence (AME) or the third cerebroventricle
(3rd V) of tethered, freely moving intact female rabbits via push-pull perfusion
(PPP). Dual cannulae for PPP and drug infusion were placed stereotaxically either
into the AME or AME and 3rd V of each rabbit after insertion of a permanent
femoral venous catheter for serial blood sampling. During an experiment,
continuous PPP samples and 10-min intermittent blood samples were collected for 5
6 hr. Females received either prazosin or control medium (artificial
cerebrospinal fluid into an AME or saline into a 3rd V cannula) for 4 hr,
beginning 1 hr before coitus. Intraventricular infusion of prazosin significantly
(P < 0.05) suppressed both the postcoital GnRH and the LH surges. Administration
of prazosin into the AME also attenuated the magnitude of the postcoital GnRH
surge (P < 0.05) whereas postcoital LH values were not decreased below that of
the control group (P > 0.05). The results suggest that alpha1 receptors are
physiologically active in the initiation of the postcoital GnRH release. These
findings, along with our earlier report of enhanced postcoital NE secretion,
reinforce the hypothesis that NE plays an essential role in the preovulatory
GnRH/LH surge in rabbits.
PMID- 9648938
TI - Dehydroepiandrosterone (DHEA) sulfate prevents reduction in tissue vitamin E and
increased lipid peroxidation due to murine retrovirus infection of aged mice.
AB - Dietary effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on
tissue antioxidants and lipids were investigated in retrovirus infected mice.
DHEA is a powerful antioxidant and immunomodulator whose production declines with
age. For this study, twenty-four female, 15-month-old C57BL/6 mice were left
uninfected while twenty-four were infected with LP-BM5 murine leukemia virus,
causing murine AIDS. The retroviral infection caused immune dysfunction and loss
of hepatic and cardiac vitamins E and A, resulting in increased lipid peroxides.
Treatment with DHEAS at 0.01 or 0.005% in drinking water for 10 weeks post
infection significantly (P < 0.05) lowered lipid peroxidation in both heart and
liver tissues. Treatment with DHEAS also largely prevented loss of the
antioxidants, such as vitamin E and A, and prevented loss of phospholipid in the
hearts and livers of the old uninfected as well as infected mice. This study
suggests that DHEAS supplementation reduces damage associated with elevated
oxidation due to aging and retrovirus infection.
PMID- 9648939
TI - Calorie restriction delays the crescentic glomerulonephritis of SCG/Kj mice.
AB - Reduced dietary calories can delay the onset and diminish the severity of murine
autoimmunities of numerous inbred and hybrid mutant strains. We sought to
determine whether the precipitous, autoimmune, crescentic glomerulonephritis of
recombinant inbred SCG/Kj mice could be abrogated similarly by calorie
restriction. Weanling SCG/Kj mice develop hematuria and proteinuria, and 50% die
as 16-week-old young adults. In this study, 113 4-week-old SCG/Kj mice were fed
either ad libitum a milled chow (Group A, n = 50), or a semipurified diet (Group
B, n = 29), or were fed a calorie-restricted semipurified diet (Group C, n = 34),
so that mice of Group C consumed approximately 32% fewer calories, but similar
amounts of essential dietary constituents as those of Group B. Calorie
restriction of Group C provided modest (P = 0.05) or substantial survival
advantage (P = 0.001) compared to the ad libitum feeding of Groups B or A,
respectively. Progression to severe glomerular pathology was delayed among Group
C mice, with more than a 5-week delay to heavy proteinuria (>100 mg/dl), a >4
week delay to hematuria, and a >5-week delay to median mortality, representing a
20% or 25% extension of median life span, compared to ad libitum-fed Group B and
A mice, respectively. Mean glomerular histopathology scores were also lower in
calorie-restricted mice compared to the ad libitum-fed cohorts (P = 0.001).
Titers of anti-ss-DNA, ds-DNA, and ANCA autoantibodies developed in weanlings
prior to the full imposition of calorie restriction and were not reduced
significantly by calorie restriction.
PMID- 9648940
TI - Prevention of crescentic glomerulonephritis in SCG/Kj mice by bone marrow
transplantation.
AB - Transplantation of MHC-compatible, T-cell-depleted, bone marrow cells has
successfully treated autoimmunities, immunodeficiencies, malignancies, and
developmental deficiencies of the hematopoietic system. Recombinant inbred SCG/Kj
mice develop spontaneous crescentic glomerulonephritis, systemic vasculitis, and
a lymphoproliferative disorder early in life. To determine whether the
precipitous autoimmune disease of SCG/Kj mice could be treated by bone marrow
transplantation, 30 SCG/Kj mice were engrafted with T-cell-depleted, bone marrow
(TCDM) from allogeneic, MHC-compatible, autoimmune-resistant C3H/He donors, and
30 SCG/Kj mice served as controls and received TCDM from syngeneic, SCG/Kj
donors. A significant survival advantage was evident from SCG/Kj mice engrafted
with C3H/He TCDM (p < 0.005), and an 89% extension of median survival compared to
recipients of SCG/Kj TCDM. Within 28 weeks post-transplantation, 62% of mice
engrafted with SCG/Kj TCDM had died with clinical signs of fatal crescentic
glomerulonephritis. This result compared with only 10% of mice engrafted with
C3H/He TCDM. Mice engrafted with SCG/Kj TCDM developed significantly greater
titers of autoantibodies to ss-DNA, ds-DNA, and myeloperoxidase (ANCA) (p <
0.001), had shorter latencies to the development of, and a greater incidence of
proteinuria, hematuria, and peripheral lymphadenopathy, and a greater mean grade
of glomerular lesion (p < 0.001), than mice engrafted with C3H/He TCDM. These
findings indicate that the genetic defect of the SCG/Kj strain of mice resides
within the hematopoietic stem cells and provokes the speculation that bone marrow
transplantation might be a useful means of treating progressive crescentic
glomerulonephritis in humans.
PMID- 9648941
TI - Circadian variation of urinary excretion of elastin and collagen crosslinks.
AB - Urinary levels of collagen- and elastin-crosslink amino acids have been used as
biologic markers for degradation of collagen and elastin in the body. Circadian
variation of collagen-crosslink amino acids is well known. The current study was
undertaken to determine whether there is also circadian variation in excretion of
elastin-crosslink amino acids. We used an isotope dilution-HPLC assay to measure
the elastin-crosslink amino acids, desmosine (DES) and isodesmosine (IDES), and
the collagen-crosslink amino acids, hydroxylysyl pyridinoline (HP) and lysyl
pyridinoline (LP), in urine. Sixteen apparently healthy subjects collected urine
from 5:00 to 7:00 AM, and from 5:00 to 7:00 PM. Mean urinary excretion of DES and
IDES in women was 56% and 41% higher (P < 0.001), respectively, in AM versus PM
specimens when normalized by the creatinine content of the urine specimen. For
men, the corresponding values were 11% and 13% higher (not statistically
significant). Mean urinary excretion of HP and LP in women was 61% and 71% higher
(P < 0.001), respectively, in AM versus PM specimens. For men, the corresponding
values were 11% and 19% higher (not statistically significant). Differences were
not found in the AM versus PM rates of excretion of creatinine in men or women.
These findings demonstrate the occurrence of circadian variation in HP, LP, DES
and IDES in women but not in men. We conclude that the time of collection of
urine specimens, especially from women, must be taken into consideration in using
the urinary levels of these crosslink amino acids as biologic markers for
collagen or elastin degradation.
PMID- 9648942
TI - Effects of dietary gamma-linolenic acid on blood pressure and adrenal angiotensin
receptors in hypertensive rats.
AB - In a previous study, we showed that dietary gamma-linolenic acid (GLA), an omega
6 polyunsaturated fatty acid found in borage oil (BOR), attenuates the
development of hypertension in young spontaneously hypertensive rats (SHR). The
purpose of this study was to determine the effects of dietary GLA on established
hypertension in adult rats, as well as its effects on components of the renin
angiotensin-aldosterone axis. For 5 weeks, male SHR (14-15 weeks old) were fed a
basal fat-free diet to which 11% by weight of sesame oil (SES) or BOR was added.
Systolic blood pressure (SBP), determined by the tail cuff method, and weight
were measured weekly. Plasma renin activity (PRA), aldosterone (PA), and
corticosterone (PC) levels were measured at the end of the dietary treatments.
The adrenal glands were homogenized, and angiotensin II (ANG II) binding was
measured and plotted according to Scatchard. Systolic blood pressure was 12 mmHg
lower at Week 5 in SHR fed the BOR diet compared to SES-fed rats (P < 0.005).
Weight gains were similar in both dietary groups. Plasma aldosterone was lower,
PRA was higher, and the PA/PRA ratio was significantly lower (P < 0.05) in BOR
fed rats. Levels of PC were the same in both groups. The BOR-enriched diet
reduced adrenal ANG II receptor density and affinity compared to the SES diet.
Results suggest that BOR inhibits adrenal responsiveness to ANG II by an action
on adrenal receptors. Our findings demonstrated that dietary GLA lowers SBP in
adult SHR. This effect may be mediated, at least in part, by interference with
the renin-angiotensin-aldosterone system at the level of adrenal ANG II
receptors.
PMID- 9648943
TI - Inhibition of gingival collagenase gene expression by dexamethasone.
AB - Glucocorticoids are potent immunosuppressants shown to be effective in the
treatment of inflammatory diseases. Reportedly, they work, in part, by inhibiting
cytokines and other transcription factors including AP-1. In this study we
investigated the mechanisms of efficient repression of collagenase gene
expression by dexamethasone in the human gingival fibroblast. Northern analyses
showed that IL-1-dependent collagenase mRNA production was significantly
decreased in the presence of dexamethasone. The influence of dexamethasone on the
transcription factor NF-kappaB, STAT3, and AP-1 was investigated by using the gel
mobility shift assay with nuclear extracts prepared from the cells grown in the
presence of dexamethasone. We observed that in addition to AP-1, binding of NF
kappaB and STAT3 to DNA was also decreased significantly. Additionally,
dexamethasone induced the transcription of the I kappaB-alpha gene suggesting
that in the presence of dexamethasone, NF-kappaB quickly reassociates with newly
synthesized I kappaB-alpha and markedly reduces the amount of NF-kappaB. CAT
transfection studies utilizing collagenase promoter demonstrated a dose-dependent
transcriptional inhibition of IL-1-induced gingival collagenase gene expression
by dexamethasone. These data reveal that collagenase gene expression can be
regulated by the impairment of IL-1-stimulated NF-kappaB, STAT3, and AP-1
activities, and can highlight a possible molecular mechanism for the anti
inflammatory effects of glucocorticoids.
PMID- 9648944
TI - Insulin-like growth factor-I and high protein diet decrease calpain-mediated
proteolysis in murine muscular dystrophy.
AB - In muscular dystrophy (MD) the imbalance between muscle protein synthesis and
degradation may be an important factor leading to muscle wasting. The three major
pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal
cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent
ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet
(HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the
effect of 6 weeks of recombinant human IGF-I (rhIGF-I) alone or in combination
with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ
dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were
included as controls). Untreated dy mice exhibited increased net proteolysis (P <
0.05), elevated net calpain activity (P < 0.01), and increased ubiquitin levels
when compared to control mice (P < 0.05). Our evidence suggests that HPD and
rhIGF-I decrease proteolysis in the 129 ReJ dy mouse. This effect appears
attributable, at least in part, to reduced calpain-mediated myofibrillar
breakdown (P < 0.05) due to decreased calpain autolysis or increased calpastatin
levels. In contrast to calpain, cathepsin B activity was increased in HPD and
rhIGF-I + HPD-treated dy muscle (P < 0.05) and unaltered in the rhIGF-I treated
animals. Levels of free and protein-conjugated ubiquitin were also increased in
rhIGF-I, and rhIGF-I + HPD treated dyanimals (P < 0.05). The amelioration of
muscle wasting in the 129 ReJ dy model by HPD and/or rhIGF-I may have potential
implications in the treatment of human MD.
PMID- 9648945
TI - Eosinophil priming and migration in idiopathic pulmonary fibrosis.
PMID- 9648946
TI - From clot to collagen: coagulation peptides in interstitial lung disease.
PMID- 9648947
TI - Chlorofluorocarbon-free inhalers: are we ready for the change?
AB - Chlorofluorocarbons (CFCs) damage stratospheric ozone permitting enhanced levels
of ultraviolet B radiation to reach the Earth's surface. As a result, production
of CFCs is now banned under the Montreal Protocol with the exception of their
temporary continued use in pressurized metered dose inhalers used to treat those
with airway disorders. Replacement propellants have now been identified and shown
to be safe and a major exercise is under way to reformulate the commonly used
aerosolized medicines with the new propellants. The new products are now
undergoing clinical trials and the first reformulated beta-agonist and
corticosteroid inhalers have reached the marketplace. The majority of the current
products will have been changed over to the new types over the next 3 yrs, and
each country will adapt a transition strategy to oversee this process. The
politicians, the environmentalists, the pharmaceutical industry and the
regulatory authorities have fulfilled their part in this changeover, and
respiratory interested health professionals now need to address what this means
for them and their patients so that there may be a seamless transition for the
millions of people who use inhaled medicines worldwide.
PMID- 9648948
TI - Eosinophil chemotactic activity in bronchoalveolar lavage from idiopathic
pulmonary fibrosis is dependent on cytokine priming of eosinophils.
AB - Increased numbers of eosinophils have been found in bronchoalveolar lavage (BAL)
fluid obtained from patients with idiopathic pulmonary fibrosis (IPF). This
suggests the presence of one or more cytokines in the lung tissue of patients
with IPF, which are involved in the induction of migration of eosinophils towards
the pulmonary compartment. To evaluate this hypothesis, we studied migratory
responses of blood eosinophils towards BAL fluid. Migratory responses were tested
by means of a modified Boyden chamber assay in 21 patients with IPF and 14
healthy controls. Experiments were performed with unprimed eosinophils and in
vitro primed eosinophils (preincubated with 10(-11) M granulocyte macrophage
colony-stimulating factor). Changes in intracellular free Ca2+ ([Ca2+]i) in
eosinophils in response to BAL fluid were also investigated, to characterize
putative chemotaxins further. Chemotactic responses of eosinophils were observed
towards BAL fluid from both patients with IPF and controls, provided that the
eosinophils were primed. No changes in [Ca2+]i in eosinophils were detected in
response to BAL fluid. Furthermore, neither a blocking antibody against
interleukin-8 nor one against regulated on activation, normal T-cell, expressed
and secreted (RANTES) influenced the response. Since a chemotactic response of in
vitro primed eosinophils was also observed towards bronchoalveolar lavage fluid
from normals, it was concluded, that in idiopathic pulmonary fibrosis, apart from
the presence of a chemotactic factor in the lung tissue, other mechanisms such as
priming of eosinophils in the peripheral blood are responsible for the
extravasation of eosinophils into the pulmonary compartment. As no changes in
[Ca2+]i were observed in the eosinophils after incubation with bronchoalveolar
lavage fluid, the chemotaxin responsible for the migratory responses is probably
not one of the known eosinophil-activating chemokines.
PMID- 9648949
TI - Ionized calcium and 1,25-dihydroxyvitamin D concentration in serum of patients
with sarcoidosis.
AB - The aim of this study was to evaluate alterations in calcium metabolism in
sarcoidosis. The serum concentrations of calcium (sCa), ionized calcium (sCa2+),
1,25-dihydroxyvitamin D (s1,25(OH)2D3) and parathyroid hormone (sPTH), serum
angiotensin-converting enzyme activity (sACE) and urinary excretion of calcium
(uCa) were studied in 36 Japanese patients with pulmonary sarcoidosis, aged
48.1+/-15.3 yrs (mean+/-SD), 15 males and 21 females. During the study the
patients were on a daily diet with 500 mg calcium and 1000 mg phosphorus for a
total of 6 days. sCa2+ was above the normal range (>1.26 mmol x L(-1)) in 10
patients (27.8%), 12 patients (33.3%) were hypercalciuric, and 16 patients
(44.4%) showed alteration in calcium metabolism, with an increase in values of
sCa, sCa2+ or uCa. There was a significant correlation between sCa2+ and
s1,25(OH)2D3 (p<0.001), as well as between sCa2+ and sACE (p<0.001). s1,25(OH)2D3
in patients with extrathoracic involvement (ETI) tended to be higher than in
patients without ETI. sCa2+ was less than 1.23 mmol x L(-1) (p<0.05) in the
majority of patients without ETI, and sCa2+ was less than 1.24 mmol x L(-1) in
the majority of normocalciuric patients. In conclusion, a disease-related
alteration in calcium metabolism was seen in about 40% of patients with
sarcoidosis, and 1,25-dihydroxyvitamin D probably plays a crucial role in this
abnormality. The serum concentration of ionized calcium was considered to be a
useful index for the disease activity of sarcoidosis.
PMID- 9648950
TI - Asbestosis, pleural plaques and diffuse pleural thickening: three distinct benign
responses to asbestos exposure.
AB - The aim of this study was to investigate by computed tomography (CT) whether
asbestosis, diffuse pleural thickening and/or pleural plaques are statistically
associated. We also tried to find criteria to differentiate between diffuse and
circumscribed pleural thickening. From 231 exposed workers, only those subjects
whose radiograph showed neither bilateral calcified pleural plaques nor small
pulmonary opacities higher than 1/1 grade according to the 1980 International
Labour Office (ILO) Classification were considered. Scans were assessed for the
presence of subpleural curvilinear lines, septal and intralobular lines,
parenchymal bands, honeycombing, rounded atelectasis, pleural plaques and diffuse
pleural thickening. CT scans revealed pleural and/or lung abnormalities in 99
workers. Pleural plaques were unilateral in one-third of cases with plaques.
Diffuse pleural thickening, parenchymal bands and rounded atelectasis were
unilateral in, respectively, 62 and 69 and 75% of cases with the abnormality.
Septal and intralobular lines, and honeycombing were always bilateral. CT signs
could be grouped into three patterns: 1) septal and intralobular lines, and
honeycombing corresponding to pulmonary fibrosis; 2) pleural plaques
corresponding to parietal pleural fibrosis; and 3) diffuse pleural thickening,
rounded atelectasis and parenchymal bands corresponding to visceral pleural
fibrosis. In these workers with a normal or near-normal radiograph, three groups
of subjects with different responses were distinguished. Crow's feet and rounded
atelectasis help to differentiate plaques from diffuse thickening.
PMID- 9648951
TI - Postoperative lung injury and oxidative damage in patients undergoing pulmonary
resection.
AB - Postpneumonectomy pulmonary oedema (PPO) complicates a significant number of
thoracic surgical procedures involving lung resection and in its extreme form is
indistinguishable from the acute respiratory distress syndrome. This study
investigated the possibility that ischaemia-reperfusion (I-R) injury contributes
to PPO via the production of damaging reactive oxygen species. In a prospective,
observational, comparative study, patients undergoing pneumonectomy, lobectomy,
or wedge resection or open lung biopsy were investigated for perioperative
changes in lung function indicative of lung injury and changes in plasma indices
of oxidative damage. Significant percentage perioperative falls in plasma protein
thiol levels (-17.9+/-7.0% for pneumonectomy, -24.3+/-5.5% for two-lobe lobectomy
and -10.2+/-2.2% for one-lobe lobectomy, p<0.05) and rises in plasma protein
carbonyl levels (26.2+/-10.5% for pneumonectomy, p<0.05, 9.8+/-7.0% for two-lobe
lobectomy and 5.0+/-2.7% for one-lobe lobectomy) were identified, but not in
patients undergoing biopsy or wedge resection. Plasma myeloperoxidase levels rose
in all groups, but not significantly. The carbon monoxide transfer coefficient
(K(CO)) fell significantly in patients undergoing lobectomy (p<0.05) but not in
those undergoing wedge resection, lung biopsy or pneumonectomy. Changes in
markers of oxidative protein damage occurred in patients undergoing lung
resection, although the gas transfer coefficient fell significantly only
following lobectomy. Oxidative damage occurs during pulmonary resection, although
associated effects on gas exchange are seen only after lobectomy.
PMID- 9648952
TI - Superimposing positive end-expiratory pressure during partial liquid ventilation
in experimental lung injury.
AB - This study was undertaken to determine the effects of superimposing incremental
levels of positive end-expiratory pressure (PEEP) during partial liquid
ventilation (PLV) on gas exchange, respiratory mechanics and morphological
changes in experimental acute lung injury (ALI). In a prospective trial, six pigs
weighing 30+/-5 kg (mean+/-SD) were tracheotomized, submitted to pressure
controlled mechanical ventilation (pc-CMV) and depleted of surfactant by lung
lavage. Animals were then mechanically ventilated with three levels of PEEP: 0.5,
1.0 and 1.5 kPa. PLV was then initiated by intratracheal instillation of 30 mL x
kg(-1) perfluorocarbon, followed by pc-CMV with PEEP 0.5, 1.0 and 1.5 kPa.
Computed tomography (CT)-based analyses of lung volumes and density were obtained
after lung lavage, in PLV and during the combined application of PLV and PEEP.
Simultaneously, haemodynamics, gas exchange, dynamic compliance (Cdyn) and
dynamic resistance (Rdyn) were determined. Statistical analysis was performed
using multivariate analyses of variance for repeated measures (p<0.05). In ALI
and before PLV, the application of PEEP significantly reduced cardiac output and
intrapulmonary shunt. Arterial oxygen tension (Pa,O2) was increased from 6.9 kPa
(52 (42, 54) mmHg) (median, (25th and 75th percentile)) to 8.6 kPa (65 (52, 133)
mmHg) (PEEP 1.0 kPa) and 15.6 kPa (117 (90, 195) mmHg) (PEEP 15 kPa) (p<0.05).
The lung volume obtained by CT increased, CT density was reduced (p<0.05), Cdyn
tended to increase and Rdyn to decrease (nonsignificant). PLV increased arterial
carbon dioxide tension and reduced pH (p<0.05). CT lung volume and lung density
were increased (p<0.05). Superimposing PEEP on PLV increased Pa,O2 from 9.3 kPa
(70 (52,124) mmHg) (PEEP 0.5 kPa) to 12.9 kPa (97 (55, 233) mmHg) (PEEP 1.0 kPa)
and 403 kPa (303 (64, 426) mmHg) (PEEP 1.5 kPa) (p<0.05), but had no significant
effect on CT lung volume and density. It was concluded that in experimental lung
injury, positive end-expiratory pressure provided alveolar recruitment. The
combined application of positive end-expiratory pressure and partial liquid
ventilation significantly augmented oxygenation and might eventually allow either
a reduction in the volumes of perfluorocarbons required, or a reduction in
positive end-expiratory pressure necessary to maintain pulmonary gas exchange in
acute lung injury.
PMID- 9648953
TI - Secretory component production by human bronchial epithelial cells is upregulated
by interferon gamma.
AB - Secretory immunoglobulin A (S-IgA) participates in the first noninflammatory line
of defence of the respiratory tract. S-IgA consists of dimeric IgA (dIgA)
produced by plasma cells and secretory component (SC) produced by epithelial
cells. This study compared SC production by primary cultures of human bronchial
epithelial cells (HBEC) and by respiratory epithelial cell lines. Among the cell
lines, A549 did not produce detectable SC, 16HBE produced very low levels of SC,
while CALU-3 produced significant levels of SC. HBEC produced SC in nonpolarized
and polarized primary cultures, where it was secreted apically. Polarized HBEC
transcytosed radiolabelled and cold dIgA, resulting in the presence of S-IgA in
their apical media. SC production and IgA transcytosis by polarized HBEC were
upregulated by interferon-gamma (IFN-gamma) after 48 h. By reverse transcription
polymerase chain reaction, no SC messenger ribonucleic acid (mRNA) was detected
in A549 and 16HBE, while SC mRNA in CALU-3 was comparable to that of HBEC
incubated for 48 h with IFN-gamma. By immunocytochemistry, HBEC expressed SC
immunostaining and its intensity increased after 48 h with IFN-gamma. It is
concluded that human bronchial epithelial cells produce secretory component and
transcytose dimeric immunoglobulin A in vitro. These processes were apically
polarized and upregulated by interferon-gamma. Among the cell lines studied, only
CALU-3 expressed secretory component-messenger ribonucleic acid and produced
detectable secretory component.
PMID- 9648954
TI - Orientation and presence of epithelium are key to endotoxin-induced neutrophil
migration.
AB - The mechanisms by which endotoxins mediate neutrophil transepithelial migration
and lung inflammation are unclear. It was hypothesized that both the presence and
orientation of epithelial cells are critical to endotoxin-induced neutrophil
migration. Neutrophil migration was compared through naked filters and filters
with A549 lung epithelial monolayers grown on the upper and lower surface of
permeable filters to simulate the apical and basal directional movement of
neutrophils, respectively. The endotoxin, Pseudomonas aeruginosa
lipopolysaccharide, was placed below the filter, acting as either a basal or an
apical stimulus. Endotoxin without serum failed to stimulate neutrophil
migration. In the presence of 1% human serum, endotoxin-induced neutrophil
migration through naked filters was dose dependent. Endotoxin-induced neutrophil
migration across A549 monolayers was minimal when the monolayers were cultured on
the upper surface of the filters (basal stimulus). In contrast, neutrophil
transepithelial migration was much greater and dependent on both dose and time
when the monolayer was cultured on the lower surface of the filter (basal to
apical neutrophil directional movement). Furthermore, enhanced neutrophil
transepithelial migration was greater with an apical than with a basal stimulus.
Endotoxin-induced neutrophil transepithelial migration was markedly inhibited
(>95%) by actinomycin D pretreatment of the monolayers, suggesting the necessity
for intact protein synthesis capacity of the A549 cells. Thus, both the presence
and orientation of airway epithelium are key in supporting endotoxin-mediated
lung neutrophilic responses.
PMID- 9648955
TI - Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young
females.
AB - We have shown previously that female sex is a determinant of cough sensitivity to
inhaled capsaicin, but the relationship between atopy and the cough sensitivity
has not been examined. The capsaicin cough threshold, defined as the lowest
concentration of capsaicin causing five or more coughs, nonspecific bronchial
responsiveness, defined as the provocative concentration of methacholine causing
a 20% fall in the forced expiratory volume in one second (PC20), total
immunoglobulin E (IgE) and specific IgEs to eight common aeroallergens (house
dust 1, 2 and 6, Dermatophagoides pteronyssinus and D. farinae, Japanese cedar,
ragweed and orchard grass) in the serum were measured in 71 nonsmoking, healthy
young women aged 20.6+/-0.1 yrs (mean+/-EM). A structured interviewer-led
questionnaire on allergic diseases revealed that one and six subjects had mild
current and past asthma, respectively. These seven subjects were excluded from
the data analysis. PC20 was significantly lower in 42 subjects showing a positive
specific IgE than in 22 subjects showing a negative specific IgE to any of the
eight allergens (p<0.05), while the capsaicin cough threshold was not
significantly different between the subgroups. PC20 was significantly lower in
subjects with positive specific IgE to Dermatophagoides and house dust, but not
to the three kinds of pollen examined. It was confirmed that atopy indicated by
specific immunoglobulin E to mite-related antigens, but not to pollen antigens,
is associated with nonspecific bronchial responsiveness, and it is suggested that
atopy is not a determinant of airway cough sensitivity in healthy, nonasthmatic
subjects.
PMID- 9648956
TI - Eosinophilic inflammation in cough variant asthma.
AB - Eosinophils are considered to play a central pathogenetic role in asthma. We
previously reported that sputum eosinophilia was observed in patients with cough
variant asthma (CVA), as well as in "classic" asthma with wheezing. This study
was undertaken to further investigate the involvement of eosinophils in CVA. The
serum eosinophil cationic protein (ECP) level, the percentage of eosinophils in
bronchoalveolar lavage (BAL) fluid, and the number of eosinophils in bronchial
biopsy specimen were examined in 14 patients with CVA, 21 with classic asthma,
and in seven healthy controls. For the two asthmatic groups, the clinical
severity was classified with scores of 1-3. Pulmonary function and bronchial
responsiveness were not significantly different between the patients with classic
asthma and those with CVA. BAL, tissue eosinophil and serum ECP were all
significantly increased in both classic asthma and CVA when compared with the
controls but were not different between classic asthma and CVA. In both groups of
asthmatics, the clinical severity significantly correlated with serum ECP and
tissue eosinophils. In conclusion, eosinophilic inflammation is involved in cough
variant asthma as well as in classic asthma. Anti-inflammatory treatment may be
essential in patients with CVA, as in those with classic asthma.
PMID- 9648957
TI - No effects of high-dose omeprazole in patients with severe airway
hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux.
AB - Acid gastro-oesophageal reflux may aggravate respiratory symptoms in patients
with asthma and chronic obstructive pulmonary disease (COPD) by increasing airway
hyperresponsiveness through vagally-mediated pathways. We wanted to determine
whether elimination of acid reflux could improve symptoms in such patients. In a
randomized, double-blind, placebo-controlled study, 36 allergic and nonallergic
subjects (17 males and 19 females, mean age 52 yrs), with airway obstruction and
severe airway hyperresponsiveness despite maintenance treatment with an inhaled
corticosteroid and with increased acid gastro-oesophageal reflux, were treated
either with omeprazole, 40 mg b.i.d., or placebo for 3 months. Primary endpoints
were: airway hyperresponsiveness, as determined by the provocative concentration
of methacholine producing a 20% fall in forced expiratory volume in one second
(PC20); and airway obstruction. Secondary endpoints were: peak expiratory flow
variability; reversibility to inhaled ipratropium bromide as a parameter of vagal
activity; asthma symptoms scores; and medication used. Reflux was measured by 24
h ambulatory intraoesophageal pH measurement. Omeprazole, 40 mg b.i.d., for 3
months had no beneficial effect on any of the pulmonary parameters, despite its
profound effect on acid reflux and improvement of reflux symptoms scores,
compared to placebo. The results of this study do not support a role for
intensive antireflux therapy to improve pulmonary symptoms and function in
patients with asthma and chronic obstructive pulmonary disease, who have severe
airway hyperresponsiveness despite maintenance treatment with inhaled
corticosteroids.
PMID- 9648958
TI - Attenuation of isocapnic hyperpnoea-induced guinea-pig bronchoconstriction by
chronic hypoxia.
AB - Chronic hypoxia has been shown to augment the production of antioxidants in rat
lungs and to reduce airway hyperreactivity in patients with asthma. This study
investigated indirectly whether this increase in antioxidants occurs in guinea
pig lungs and whether the increased antioxidants affect hyperpnoea-induced
bronchoconstriction (HIB). Guinea-pigs were divided into four groups: control
(n=8); chronic hypoxia (n=7); capsaicin pretreatment (n=7); and capsaicin
pretreatment plus chronic hypoxia (n=8). Control animals were not treated.
Animals in the hypoxia group were intermittently exposed to an ambient pressure
of 380 mmHg for 7 days. A five day pretreatment of capsaicin was used to deplete
tachykinins. In the last group, animals were pretreated with capsaicin, followed
by a seven day hypoxic exposure. On the day of the study, airway function was
examined in the anaesthetized and paralysed animal. Fifteen minutes of hyperpnoea
caused marked decreases in the maximal expiratory flow rate at 15% vital
capacity, forced expiratory volume in one second, and dynamic respiratory
compliance, indicating HIB. This HIB and plasma substance P levels were
significantly attenuated by chronic hypoxia, capsaicin pretreatment, and
capsaicin pretreatment plus chronic hypoxia. Furthermore, chronic hypoxia
attenuated airway constriction induced by xanthine-xanthine oxidase. The results
suggest that chronic hypoxia attenuates hyperpnoea-induced bronchoconstriction
via a decrease in the oxygen radical-mediated release of tachykinins.
PMID- 9648959
TI - Bronchodilator response to salbutamol after chronic dosing with salmeterol or
placebo.
AB - It has been hypothesized that regular inhaled beta2-agonist therapy causes
desensitization of beta2-receptors. The aim of this study was to define whether
beta2-receptor desensitization occurs after treatment with the long-acting beta2
agonist salmeterol, assessed by measuring the bronchodilator response to
cumulative repeated doses of inhaled salbutamol before and after treatment. Forty
nine stable adult patients with asthma were randomized to receive either
salmeterol 50 microg b.d. or placebo b.d. from an Accuhaler for 4 weeks after an
initial 2 week run-in period without beta2-agonists. All patients were receiving
inhaled corticosteroids. Bronchodilator responsiveness to cumulative repeated
doses of inhaled salbutamol were measured before and 12 and 36 h after the last
dose of study treatment. The primary efficacy endpoint was the peak forced
expiratory volume in one second (FEV1) response before and after treatment. There
were no significant differences between the two treatment groups in the absolute
peak FEV1 or maximal peak expiratory flow (PEF) results 12 or 36 h after the last
dose of study treatment. Significantly higher clinic lung function and diary card
parameters were noted in the salmeterol group when compared to the placebo
treated patients, demonstrating the beneficial effects of regular salmeterol.
Regular salmeterol usage did not lead to reduced efficacy of usual or higher than
usual doses of salbutamol.
PMID- 9648960
TI - Bronchodilator response to salbutamol after spontaneous recovery from nonspecific
bronchial provocation tests in asthma.
AB - Assessment of airway responsiveness by bronchoprovocation and bronchodilatation
tests is important in the diagnostic work-up protocol of bronchial asthma and it
would be convenient to undertake both tests on the same occasion. However, it is
not known whether this can be done accurately. Therefore, this study evaluated
the effect of a prior bronchial provocation test on the bronchodilator response
to salbutamol after spontaneous recovery of the forced expiratory volume in one
second (FEV1) in a group of asthmatic subjects. On two separate occasions at the
same time of day, concentration-response studies with inhaled histamine or
methacholine, or a sham challenge with normal saline were carried out in a
blinded, randomized manner. Changes in airway calibre were followed as FEV1 and
agonist responsiveness expressed as the provocative concentration causing a 20%
fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait
of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol
from a metered dose inhaler with a spacer. The bronchodilator response to
salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init).
Bronchial challenge with both agonists failed to alter significantly the airway
response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9%
(9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge
day respectively. It was shown that the degree of bronchodilatation achieved
after salbutamol 200 microg is not affected by prior bronchoprovocation testing
when enough time is allowed for the airways to recover spontaneously to baseline
forced expiratory volume in one second. Thus evaluation of airway responsiveness
by both bronchial provocation tests and bronchodilator testing can be assessed
reliably within a few hours in asthmatic patients.
PMID- 9648961
TI - Tolerance to the protective effects of salmeterol on methacholine-induced
bronchoconstriction: influence of inhaled corticosteroids.
AB - Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway
responsiveness for at least 12 h, but this effect seems to decrease with regular
use. We evaluated the time-course of the protective effects of salmeterol on
methacholine-induced bronchoconstriction, its modulation by inhaled
corticosteroids (ICS) and its influence on asthma control. Thirty two subjects
(13 males and 19 females) with mild to moderate stable asthma were divided into
two groups according to their medication needs: bronchodilators (BD) alone (n=16)
or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study
was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or
a placebo for 4 weeks each in random order, separated by a 2 week washout period.
The provocative concentration of methacholine causing a 20% fall in forced
expiratory volume in one second (PC20) was measured before and after each
treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h
after. Baseline forced expiratory volume in one second (FEV1) increased
significantly after salmeterol, both after the first dose and at 4 weeks (BD
group: 19 and 17%; ICS: 22 and 13%). On the first day of administration,
salmeterol provided significant protection in both groups up to 12 h with a PC20
before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively,
in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group.
After 4 weeks, this effect was significantly attenuated in both groups with a
PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively,
in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group.
This loss of protective effect was of similar magnitude in both groups.
Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change
significantly throughout the study in both groups. In conclusion, the
bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h
postdose; inhaled corticosteroids did not prevent this reduction. However, the
development of tolerance was not associated with loss of asthma control.
PMID- 9648962
TI - Platelet-activating factor increases leukotriene B4 release in stimulated
alveolar macrophages from asthmatic patients.
AB - This study was designed to examine further the role of platelet-activating factor
(PAF) in asthma, comparing leukotriene B4 (LTB4) release, 5-lipoxygenase activity
and intracellular calcium levels ([Ca2+]i) in macrophages. LTB4 and other
lipoxygenase metabolites in macrophages in bronchoalveolar lavage fluids obtained
from 23 asthmatic patients and 20 control subjects were measured by reverse-phase
high-performance liquid chromatography. [Ca2+]i was monitored using the
fluorescent probe fura-2. The basal LTB4 release of resting macrophages was not
different between groups (0.02+/-0.01 versus 0.05+/-0.02 ng x 10(-6) cells). When
stimulated with calcium ionophore A23187 (2.5 microM), however, macrophages from
asthmatic patients released more LTB4 than cells from control subjects (30.2+/
3.4 versus 13.7+/-2.1 ng x 10(-6) cells). Although PAF alone did not alter LTB4
release, it enhanced the response to subsequent A23187 stimulation. This effect
was noted following short treatment (i.e., 5 min) at concentrations of > or =1.0
microM PAF, with the maximal effect noted after treatment with 5.0 microM PAF +
2.5 microM A23187 (105.1+/-6.7 versus 15.3+/-2.6 ng x 10(-6) cells). Treatment of
macrophages with PAF also increased 5-lipoxygenase activity and [Ca2+]i more in
cytosols from asthmatic patients than in cytosols from control subjects. These
findings support a role of intracellular calcium in the activation of 5
lipoxygenase which, in turn, augments the release of leukotriene B4. Because
levels of platelet-activating factor may be increased in the lung during asthma
and can increase the subsequent release of a chemotactic mediator leukotriene B4,
from macrophages, these findings suggest that platelet-activating factor may
prime the constitutive cells of the lung to augment inflammatory effects
important in the pathogenesis of asthma.
PMID- 9648963
TI - Effect of slow-release theophylline on nasal antigen challenge in subjects with
allergic rhinitis.
AB - It has been recognized recently that theophylline possesses anti-inflammatory
effects that could be of clinical interest in patients with airway inflammatory
diseases such as asthma and allergic rhinitis (AR). The aim of the present study
was to explore the effect of theophylline on the nasal eosinophilic inflammatory
response following allergen challenge in patients with AR. Fourteen subjects
suffering from seasonal rhinitis with an early reaction after nasal allergen
provocation were challenged outside the pollen season after pretreatment for 3
weeks with placebo or slow-release theophylline (Euphylong in a randomized double
blind, cross-over study. Nasal blocking index (NBI), nasal airway resistance and
symptoms were recorded before, and 1 and 5 h after challenge; additionally, nasal
lavage fluid was collected before, as well as 1 and 5 h after challenge.
Eosinophil cationic protein (ECP) was measured in the lavage as well as the
number of eosinophils before, and 1 h and 5 h after allergen challenge. After 3
weeks of treatment, baseline concentrations of ECP in nasal lavage amounted to
826+/-329 ng x L(-1) (placebo) and 936+/-351 ng x L(-1) (theophylline). The ECP
levels did not increase during the early phase response. Five hours after
challenge, ECP in the placebo group increased markedly (p<0.01), whereas no
significant increase was observed during theophylline treatment. In parallel, the
number of eosinophils in the nasal lavage fluid was lower during theophylline
treatment. Additionally, theophylline therapy also significantly reduced the
nasal symptoms and had some protective effect against nasal obstruction following
allergen challenge. These results confirm the anti-inflammatory effects of
theophylline and suggest that these effects may be of clinical benefit in
patients with allergic rhinitis.
PMID- 9648964
TI - Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children
with asthma.
AB - The study aimed to investigate dose consistency and particle distribution from
the dry powder inhalers Diskus and Turbuhaler. Full profiles of inhalation
pressure versus time were recorded in 18 4 yr old and 18 8 yr old asthmatic
children through Diskus and Turbuhaler inhalers. These data were used in an
inhalation profile simulator to assess drug delivery from both a Diskus inhaler
and a Turbuhaler inhaler, and in particular to assess the proportion of drug
emitted in the coarse (>4.7 microm) and fine (<4.7 microm) particle size range
from each type of inhaler. The inhalation profile more accurately represents the
changes in flow rate over time through the device than the constant flow rate
usually applied with an impactor alone. The aerosol cloud was released before the
peak inspiratory effort had been achieved and accordingly the early part and not
the peak of the inspiratory performance is a determinant of the quality of the
aerosol. The mean (SD) amount of drug in large particles (>4.7 microm), fine
particles (<4.7 microm) and very fine particles (<2.1 microm) in percentage of
label claim from the Fluticasone Diskus was 72 (5), 15 (2) and 2 (1) from the 4
yr old children and 71 (3), 18 (2) and 2 (1) from the 8 yr old children,
respectively. Similar particle fractions from the Budesonide Turbuhaler were 35
(9), 21 (10) and 7 (5) from 4 yr old children and 30 (7), 32 (9) and 12 (6) from
8 yr old children. In conclusion, the Diskus inhaler provides an improved dose
consistency through the varying age groups and inspiratory flow performances when
compared to the Turbuhaler in terms of the proportion of the dose emitted at each
particle size. This improvement is at the expense of a low fine particle mass and
a high proportion of coarse particles from the Diskus as compared with the
Turbuhaler.
PMID- 9648965
TI - Prospective evaluation of World Health Organization criteria to assist diagnosis
of tuberculosis in children.
AB - Because of the difficulty in confirming childhood tuberculosis (TB), the World
Health Organization (WHO) proposes a hierarchical approach to diagnosis using
history and certain clinical features to help to improve the control of TB in
communities. The objective of this study was to evaluate prospectively in
children the diagnostic value of recent weight loss or failure to gain weight
adequately, cough or wheezing for >2 weeks and recent household contact with an
adult case of pulmonary TB. These evaluations were performed in 627 children
presenting to the paediatric outpatient department of a tertiary hospital
situated in the Western Cape Province of South Africa and serving a community
with a very high incidence of TB (>1,000 per 100,000). If at least one of the
criteria was present, the diagnosis of TB was investigated further by clinical
investigation, Mantoux test, chest radiography and TB culture from gastric
aspirate. One or more of the proposed criteria for diagnosing TB in childhood
were present in 206 children (33%). TB confirmed by culture of Mycobacterium
tuberculosis from gastric aspirate was found in 10 children (5%). After
diagnostic work-up, 23 children (11%) were considered to have probable TB,
whereas 173 (84%) were, after follow-up of 8 weeks, thought not to have TB. In
this study the simultaneous presence of the three WHO criteria for suspecting TB
had a positive predictive value of 63%. These results should assist in the more
precise delineation of the predictive value of the proposed World Health
Organization approach to the diagnosis of tuberculosis in childhood.
PMID- 9648966
TI - Influence of correction of flow limitation on continuous positive airway pressure
efficiency in sleep apnoea/hypopnoea syndrome.
AB - We evaluated the efficiency of two different treatment procedures with continuous
positive airway pressure (CPAP) on sleep, nocturnal breathing characteristics and
daytime vigilance in 18 newly diagnosed patients with untreated sleep
apnoea/hypopnoea syndrome (SAHS) randomly allocated to two different groups. In
group I, the positive pressure (PP) level was set to suppress flow limitation
(PFL), while in group II the PP was set at a level that eliminated only
apnoea/hypopnoea and snoring (PAHS). At the end of a 3 week period of home CPAP
therapy, a follow-up sleep study, vigilance and cognitive tests were made.
Overall, PFL was significantly higher than PAHS values (PFL: 10.42.6 cmH2O; PAHS:
8.9+/-2.6 cmH2O; p<0.01, mean+/-SD). We found no difference in sleep quality,
nocturnal saturation and apnoea/hypopnoea index, or in daytime vigilance tests
between the two groups at the end of the treatment period. However, there was a
significantly greater scattering in the changes of sleep latency in group II than
in group I. This was associated with a significant difference in the daily
duration of nasal CPAP use between the two groups (group I: 7.29+/-0.95 h x day(
1); group II: 6.01+/-0.94 h x day(-1); p=0.01) and with a positive correlation
between final maintenance of wakefulness test values and the duration of CPAP use
(p<0.05; r=0.55). These results tend to show that correcting flow limitation is
associated with a higher observance and a more important efficiency in
normalizing daytime vigilance than with conventional nasal continuous positive
airway pressure.
PMID- 9648967
TI - Forced oscillation technique for the evaluation of severe sleep apnoea/hypopnoea
syndrome: a pilot study.
AB - The forced oscillation technique (FOT) is a noninvasive method of potential
clinical interest for quantitatively assessing airway mechanics during sleep. We
investigated the applicability of FOT as a diagnostic tool for noninvasive
assessment of airflow obstruction in patients with sleep apnoea/hypopnoea
syndrome (SAHS) during sleep. In seven patients previously diagnosed with severe
SAHS (mean+/-SD apnoea/ hypopnoea index (AHI) 67+/-14) we performed a full
polysomnography (PSG) together with on-line measurement of respiratory impedance
(IZI) using FOT. For each patient we determined: 1) number of respiratory events
conventionally detected by full PSG, those obtained by FOT and their degree of
concordance; and 2) the characteristics and values of IZI during the respiratory
events. FOT was well tolerated and easily applied in conjunction with a
conventional sleep setup. The mean number of respiratory events x h(-1) detected
by PSG and FOT were 55+/-16 and 58+/-17, respectively, with a strong concordance.
IZI increased from a baseline of 11+/-4 to 50+/-20 cmH2O x L(-1) x s during
apnoea (mean+/-SD). In all but one patient intermittent increases of IZI occurred
immediately before each obstructive apnoea. In four patients, the increases of
IZI developed at end-expiration whereas in two others occurred during
inspiration. During hypopnoea most of the patients showed decreases of IZI during
expiration. In conclusion, forced oscillation technique can be used as a
noninvasive and complementary tool for the diagnosis of respiratory events and
provides an on-line quantitative approach for continuous monitoring of airflow
obstruction during sleep in patients with sleep apnoea/hypopnoea syndrome.
PMID- 9648968
TI - Spectral analysis of wakefulness and REM sleep EEG in patients with sleep apnoea
syndrome.
AB - Neuropsychological investigations of patients with obstructive sleep apnoea
syndrome (OSAS) have shown impairments in such basic functions as memory,
attention and executive control. Since executive functions are known to be
dependent on the integrity of the frontal lobe, it was hypothesized that OSAS may
be associated with hypoxaemic frontal lobe dysfunction. To test this hypothesis,
21 apnoeic patients and 10 normal controls were studied with quantitative
electroencephalographic (EEG) methods during rapid eye movement (REM) sleep, when
most apnoeic events occur and during wakefulness. In apnoeic patients, EEG
slowing in REM sleep was observed over frontal, central and parietal regions,
while EEG slowing during wakefulness was observed over all cortical regions
examined. A positive correlation was found between EEG slowing during wakefulness
and oxygen desaturation during the night. Contrary to the hypothesis, these
electroencephalographic changes were not localized only to the frontal region.
This result may explain the wide range of neuropsychological deficits noted in
patients with obstructive sleep apnoea syndrome, in addition to their poor
performance in tasks of executive functioning.
PMID- 9648969
TI - A comparison of three methods of measuring 99mTc-DTPA lung clearance and their
repeatability.
AB - The lung clearance of technetium-99m diethylenetriamine penta-acetic acid (99mTc
DTPA) is a measure of respiratory epithelial permeability. Many factors may
contribute to the wide range of normal values, including the method of correction
for background activity. The aim of this study was to compare three methods of
analysis, including their repeatability. 99mTc-DTPA lung clearance imaging was
performed on eight nonsmokers (age 32+/-2 yrs, forced expiratory volume in one
second (FEV1) 102.8+/-3.3% predicted yrs, mean+/-SEM and seven smokers (age 46+/
4 yrs, p<0.01, versus nonsmokers; FEV1 88.9+/-8.9%, p<0.05 versus nonsmokers) on
two occasions each. The smokers were asked to refrain from smoking for 12 h. An
uncorrected analysis was compared with two methods corrected for recirculating
background activity using an intravenous correction and inter-renal and shoulder
background regions of interest. The uncorrected method gave higher mean values
for 50% lung clearance of 99mTc-DTPA (t50) values than the inter-renal (p<0.001)
and shoulder (p<0.001) methods of correction in nonsmokers and the inter-renal
method gave lower values than the shoulder-corrected method (p<0.05). In smokers
there was no difference. There were no differences in mean t50 values obtained on
two separate visits. There was no difference in the repeatability of the three
methods of analysis. The three methods of analysis produced comparable results
with no differences in repeatability.
PMID- 9648970
TI - Common fears of patients undergoing bronchoscopy.
AB - In the world of medical literature, little has been reported about the fears of
patients undergoing bronchoscopy. The aim of this study was to identify the
common fears of patients undergoing fibreoptic bronchoscopy and to determine
whether any factors might contribute to reducing these fears. One hundred and
four consecutive patients undergoing bronchoscopy were interviewed. Sixty one
patients expressed fear about the procedure, as follows: afraid of pain (33);
afraid of breathing difficulties (11); afraid of oropharyngeal irritation (5);
afraid of the bronchoscopy findings (2); afraid of sedation, cross-infection and
nasal lignocaine spray, respectively (3); and unable to be specific (7). There
was no difference between the "no fear" and "fearful" groups in ethnicity, source
of referral, education, previous endoscopy, doctors' explanation and the
patients' understanding of the procedure and its indication. "Fearful" patients
were significantly younger (t=2.082, p=0.037) and female (chi2=4.180, p=0.038).
Doctors were more likely to explain the indication for bronchoscopy than how it
would be performed (chi2=6.403; p=0.011), and patients were more likely to
understand why they needed a bronchoscopy than how it would be performed
(chi2=21.505; p<0.001). Fear preceding bronchoscopy is independent of patients'
demographic features except for age and gender. Doctors tend to explain "why" but
not "how" the procedure is performed. Provision of detailed information about
sensations that are likely to be experienced in bronchoscopy could be used to
allay some of these common fears.
PMID- 9648971
TI - Treatment of ventilatory failure in the Prader-Willi syndrome.
AB - Hypercapnic respiratory failure is a common cause of death in the Prader-Willi
syndrome. Its relationship to sleep-disordered breathing has not been established
and there are no reports of its successful treatment. We have retrospectively
reviewed the records of four patients with the syndrome, who developed
ventilatory failure. Daytime arterial blood gas tensions and overnight oximetry
traces before and during treatment were compared. Each patient had severe sleep
disordered breathing in association with daytime ventilatory failure. The median
overnight mean arterial oxygen saturation (Sa,O2) was 82% and the median minimum
was only 41.5%. Initial treatment was with nasal intermittent positive pressure
ventilation, and in each case the daytime arterial blood gas tensions were
normalized. The patients were maintained on nasal continuous positive airway
pressure at night after discharge. Compliance has been good, and at last follow
up (after a median of 4.8 yrs) the daytime arterial gas tensions remained normal,
while the median overnight mean arterial oxygen saturation was 95.5% and the
median minimum was 84.5%. This study of patients with the Prader-Willi syndrome
shows that daytime ventilatory failure is associated with sleep-disordered
breathing. It can be reversed with nocturnal noninvasive ventilation and
maintenance treatment with continuous positive airway pressure is well tolerated,
with no deterioration in respiratory parameters.
PMID- 9648972
TI - Pulmonary vascular disorders in portal hypertension.
AB - The wide spectrum of pulmonary vascular disorders in liver disease and portal
hypertension ranges from the hepatopulmonary syndrome characterized by
intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary
hypertension), in which pulmonary vascular resistance is elevated. Since
hepatopulmonary syndrome and portopulmonary hypertension have been reported in
patients with nonhepatic portal hypertension, the common factor that determines
their development must be portal hypertension. The clinical presentations are
very different, with gas exchange impairment in the hepatopulmonary syndrome and
haemodynamic failure in portopulmonary hypertension. The severity of
hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas
no simple relationship has been identified between hepatic impairment and the
severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome
is common after liver transplantation, which has an uncertain effect in
portopulmonary hypertension. The pathophysiology of both syndromes may involve
vasoactive mediators and angiogenic factors.
PMID- 9648973
TI - Effect of inhaled corticosteroids on bones and growth.
AB - Inhaled corticosteroids are recognized as the most effective anti-inflammatory
therapy in patients with asthma and their early introduction is recommended by
national and international guidelines. Concerns have been raised about potential
adverse effects of inhaled corticosteroids on bones and growth, as these appear
to be more important clinically than effects on the hypothalamic-pituitary
adrenal axis, which are more commonly measured. This review examines the effects
of inhaled corticosteroids on biochemical bone markers, bone density and growth
in adults and children with asthma, in view of the recent availability of a
substantial amount of new clinical trial data. Examination of relevant
retrospective and prospective data, involving 11 studies (1,240 patients) on
biochemical bone markers and 14 studies (373 patients) on bone density over a
wide dose range, have largely indicated no significant or clinically important
effect on these measurements in adults or children with asthma. Markers of bone
formation and resorption need to be measured concurrently for a reliable
assessment of bone turnover to be made. Knemometry, measuring lower leg growth
rate, is a sensitive technique for comparing the systemic activity of different
inhaled corticosteroids, but does not relate to long-term growth. The majority of
approximately 40 studies on inhaled corticosteroids and statural growth in
children, over a wide recommended dose range, including a number of recent long
term, prospective studies, demonstrate little or no effect. Children taking above
recommended doses of inhaled corticosteroids should have their growth monitored
using stadiometry at least every 6 months by trained personnel. Most of the areas
reviewed, particularly the relatively new areas of biochemical bone markers and
bone density, require further properly controlled, long-term, prospective
investigation, although the long-term value of bone markers appears limited. In
summary, the data as it currently stands, suggests that doses of inhaled
corticosteroids up to 1,000 microg x day(-1) in adults and 400 microg x day(-1)
in children have no significant effect on bones and growth in the large majority
of patients with asthma.
PMID- 9648974
TI - The role of "fear of corticosteroids" in nonparticipation in early intervention
with inhaled corticosteroids in asthma and COPD in general practice.
AB - Treatment of chronic airflow obstruction with inhaled corticosteroids at an early
stage has been shown to preserve the lung function. We tested the hypothesis that
"fear of corticosteroids" may be an important reason for nonparticipation in the
Detection, early Intervention and Monitoring programme on Chronic obstruction
pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred
and forty nine adult subjects from 10 general practices were invited to
participate in the several parts of the "DIMCA" programme. Refusers were
questioned about the reason(s) for nonparticipation. Together the screening,
monitoring and three drug interventions of the study showed on average 25-35%
refusers. The most frequent reasons for nonparticipation were absence of
pulmonary symptoms and lack of time. For those invited to take part in one of the
three drug interventions, "dislike of medication" was the most important reason
for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids"
specifically was the reason for nonparticipation in 8% of the refusers on the
basis of "dislike of medication". We concluded that a specific fear of
corticosteroids was not a major obstacle for early intervention with inhaled
corticosteroids.
PMID- 9648975
TI - Occupational asthma caused by aluminium welding.
AB - Work-related asthma has been documented in workers employed in the primary
aluminium industry and in the production of aluminium salts. The role of
aluminium in the development of occupational asthma has, however, never been
convincingly substantiated. We investigated a subject who experienced asthmatic
reactions related to manual metal arc welding on aluminium. Challenge exposure to
aluminium welding with flux-coated electrodes, as well as with electrodes without
flux, elicited marked asthmatic reactions. Manual metal arc welding on mild steel
did not cause significant bronchial response. The results of inhalation
challenges combined with exposure assessments provided evidence that aluminium
can cause asthmatic reactions in the absence of fluorides. Awareness of this
possibility may be relevant to the investigation of asthma in workers exposed to
aluminium.
PMID- 9648976
TI - Alpha-fetoprotein producing pulmonary blastoma in a patient with systemic
sclerosis: pathogenetic analysis.
AB - We describe a rare case of pulmonary blastoma complicated with systemic
sclerosis. The serum alpha-fetoprotein level was elevated at presentation and the
biopsied tumour stained positively against anti-alpha-fetoprotein antibody. The
alpha-fetoprotein produced autonomously by tumour cells was of yolk-sac origin.
Although the pathogenesis of pulmonary blastoma has not been clarified, we
suggest that this pulmonary blastoma is a type of yolk-sac tumour.
PMID- 9648977
TI - Bronchial stenosis and sclerosing mediastinitis: an uncommon complication of
external thoracic radiotherapy.
AB - The side-effects of radiation therapy on the bronchial tree or on the mediastinum
are seldom reported. In this setting, we report a case of sclerosing
mediastinitis with bronchial stenosis discovered 1 yr after external radiotherapy
for lung cancer. The patient was treated with a Dumont stent and has so far had
an uneventful further course for up to 42 months. Bronchial stenosis related to
mediastinal fibrosis after radiotherapy has not been reported previously.
PMID- 9648978
TI - An unusual case of Hughes-Stovin syndrome.
AB - In 1959 HUGHES and STOVIN described a syndrome consisting of multiple pulmonary
aneurysms and peripheral venous thrombosis. Since that time several cases of the
Hughes-Stovin syndrome have been published. We present the case of a 25 yr old
man who, in addition to the classical symptoms, had multiple aneurysms of the
bronchial arteries, which were the cause of severe haemoptysis. An aneurysm of
the left hepatic artery was also detected. To our knowledge this is the first
description of aneurysms of the bronchial arteries in Hughes-Stovin syndrome.
Bleeding was successfully treated by double embolization of bronchial arteries
via transfemoral catheter.
PMID- 9648979
TI - Comparative assessment of safety and efficacy of inhaled corticosteroids: report
of a committee of the Canadian Thoracic Society.
PMID- 9648980
TI - Evaluation of a commercial infant body plethysmography.
PMID- 9648981
TI - Barrett's oesophagus: pathophysiology, diagnosis, and management.
PMID- 9648982
TI - Gastric ulcer, atrophic gastritis, and intestinal metaplasia caused by
Helicobacter pylori infection in Mongolian gerbils.
AB - BACKGROUND: Helicobacter pylori infection is associated with gastroduodenal
disease in humans. In this study we aimed to show this relationship directly in
Mongolian gerbils. METHODS: The animals were challenged orally with H. pylori and
killed 1, 2, 3, and 6 months after inoculation for histologic and anti-H. pylori
antibody titer examination. RESULTS: The spiral bacteria were observed in the
mucus and gastric pits of all infected animals. A severe infiltration of the
lamina propria by polymorphonuclear and mononuclear cells was seen 1 month after
H. pylori inoculation. The submucosa was infiltrated by mainly mononuclear cells
with formation of lymphoid follicles. Erosion of the gastric mucosa appeared soon
after inoculation, whereas gastric ulcers, gastritis cystica profunda, and
atrophy with goblet cell metaplasia occurred between 3 and 6 months after
inoculation. In the duodenal mucosa a mild inflammatory cell infiltration with
ballooning and diminished number of duodenal glands was seen. The IgG anti-H.
pylori antibody titer increased gradually after 2 months of inoculation.
CONCLUSIONS: Since the gastritis, gastric ulcers, atrophic gastritis, and
intestinal metaplasia that developed in Mongolian gerbils were similar to those
observed in humans, this model may be useful to study the therapy of gastric
ulcer and, with a longer observation period, to confirm a possible relationship
between H. pylori and malignancy.
PMID- 9648983
TI - Effects of Helicobacter pylori eradication on gastric function indices in
functional dyspepsia. A prospective controlled study.
AB - BACKGROUND: To date, it is unclear whether Helicobacter pylori infection is
associated with disturbances of gastric emptying or acid secretion in patients
with functional dyspepsia (FD). Our aim was to investigate whether, in the long
run, cure of H. pylori infection significantly influences gastric emptying of
solids, acid secretion, and gastrin and pepsinogen I (PGI) release in patients
with FD. METHODS: Thirty-eight consecutive H. pylori-positive patients with FD,
whose complaints were scored for severity and frequency on the basis of a
validated symptom questionnaire, were initially enrolled in the study. They were
randomized to receive an eradicating regimen consisting of omeprazole plus
clarithromycin and tinidazole for 1 week or full-dose ranitidine for 3 weeks. In
33 patients (18 H. pylori-cured and 15 with persistent infection) basal and
pentagastrin-stimulated acid secretion, fasting and meal-induced gastrin
concentrations, fasting serum PGI levels, and gastric emptying of solids were
determined before and 6 months after therapy. RESULTS: In the 18 H. pylori-cured
patients meal-induced gastrin and fasting PGI levels were significantly reduced
after 6 months as compared with pretreatment values (peak serum gastrin, 76.0 +/-
23.4 versus 111.9+/-37.4 pg/ml; PGI, 57.1+/-23.4 versus 72.9+/-29.1 ng/ml),
whereas they remained virtually unchanged in the 15 patients with persistent
infection. In contrast, both basal and stimulated acid secretion and gastric
emptying time of solids remained unmodified over time in both groups of patients.
CONCLUSIONS: We confirm that also in patients with functional dyspepsia H. pylori
eradication in the long run significantly reduces gastrin and PGI release as a
result of improvement in the underlying antral gastritis, but this is not
accompanied by modifications of gastric emptying of solids or acid secretion.
PMID- 9648984
TI - Variation in the 13C-urea breath test value by nationality in Helicobacter pylori
infected children.
AB - BACKGROUND: The 13C-urea breath (13C-UBT) test value is (semi-)quantitatively
related to Helicobacter pylori density in the gastric antrum, and the value
correlates with the grade of gastritis. The aim of this study was to assess
variation of the 13C-urea breath test value by sociodemographic factors in H.
pylori-positive children. METHODS: The analysis was performed on 127 asymptomatic
children (aged 5-7 years) who were identified as H. pylori-positive with the 13C
UBT test in a large population-based epidemiologic study in the city of Ulm
(southern Germany). The parents of the children were asked to fill out a
standardized questionnaire about sociodemographic data. RESULTS: Forty-two
infected children (33.1%) were of German nationality, 47 children (37.0%) were of
Turkish and 38 children (29.9%) were of another nationality. Turkish children had
a significantly higher 13C-UBT value (geometric mean = 27.2%) than German
children (16.7%) or children with another nationality (19.3%) (P < 0.001). Girls
had a trend towards higher values than boys (P = 0.058 after adjustment for
nationality). Body mass index, education of the parents, and prior use of
antibiotics were unrelated to the extent of the 13C-UBT. CONCLUSIONS: This study
identified significant variation in the extent of the 13C value by nationality
among H. pylori-infected children. Further studies are needed to elucidate the
causes and potential consequences of these variations.
PMID- 9648985
TI - What is normal oesophageal motility? An ambulatory study.
AB - BACKGROUND: Our aim was to establish normal values for wave characteristics and
patterns in long-term ambulatory oesophageal body motility. METHODS: A pressure
sensor was positioned in the pharynx or cricopharyngeus for swallow detection.
Oesophageal body pressures were recorded 5, 10, and 15 cm above the lower
oesophageal sphincter. Contraction patterns and wave characteristics from eating,
drinking, and postprandial, fasting, and supine periods in 16 healthy subjects
were studied. RESULTS: Contraction patterns were similar during eating and
drinking periods or fasting and postprandial periods (P > 0.05). Wave
characteristics during each period differed significantly in amplitude, duration,
area under the curve, or peristaltic velocity (P < 0.05). During the eating
period the amplitude and area under the curve were greatest, and peristaltic
velocity was slowest compared with all other periods. CONCLUSIONS: Data from the
eating and drinking periods or the fasting and postprandial periods can be
combined for contraction pattern analysis but not for wave characteristic
analysis, for which data from different periods should be analysed separately.
PMID- 9648986
TI - Flow across the human pylorus soon after ingestion of food, studied with duplex
sonography. Effect of glyceryl trinitrate.
AB - BACKGROUND: By means of duplex sonography, gastric emptying can be related to
antral motor activity. The aim of this study was to examine gastric emptying in
relation to antral contractions during and immediately after ingestion of a
liquid meal in healthy subjects and to study the effect of glyceryl trinitrate
(GTN) on this early phase of gastric emptying. METHODS: Ten healthy, non-smoking
men (median age, 36 years; range, 29-41 years) were studied twice on separate
days, once without drug administration and once after taking a 0.5-mg sublingual
GTN tablet 3 min before ingesting 500 ml of a meat soup (20 kcal; Toro). The
subjects were investigated during 3 min of fasting, during 3 min of drinking the
soup, and during the first 10 min postprandially. RESULTS: Transpyloric forward
flow commenced on average 80 sec and 95 sec after the start of drinking the soup
without and with GTN, respectively (P = NS). Non-contractile, pulsatile
transpyloric flow (that is, pendulating, transpyloric flow not associated with
antral contractions) occurred during episodes of concurrent relaxation of the
terminal antrum, the pylorus, and the duodenal bulb. This type of flow occurred
mainly just before the start of contractile, pulsatile transpyloric flow
(associated with propulsive antral contractions). Initial non-contractile,
pulsatile transpyloric flow before commencement of contractile, pulsatile
transpyloric flow lasted longer with GTN (188 sec) than without GTN (25 sec) (P <
0.05). Consequently, contractile, pulsatile transpyloric flow commenced later
with GTN (302 sec) than without (102 sec) (P < 0.05). CONCLUSIONS: Non
contractile transpyloric flow seems to be a physiologic phenomenon during the
early phase of gastric emptying. GTN prolongs the initial phase of non
contractile, and delays the onset of contractile, pulsatile transpyloric flow.
PMID- 9648987
TI - Identification of coeliac disease in primary care.
AB - BACKGROUND: Coeliac disease is common yet often undiagnosed because symptoms may
be trivial, non-specific, or non-gastrointestinal, or because of lack of
clinician awareness. Serum IgA-class endomysial antibodies (EmA) have high
specificity for coeliac disease and may facilitate case-finding by clinicians
other than gastroenterologists. We assessed the appropriateness and diagnostic
yield of of requests for EmA by primary care general practitioners in a defined
geographic area of Northern Ireland. METHODS: We identified patients who had EmA
examination requests by their general practitioners during 1994-1996. Individual
patient questionnaires were posted to the general practitioners concerned,
seeking information on indications for testing, management after the result, and
final diagnosis. We compared new patient diagnosis rates in two catchment areas,
one served by a large district general hospital with, and the other by smaller
hospitals without, a medical gastroenterology facility. RESULTS: A total of 239
patients had coeliac profile testing by 69 of 177 general practitioners in the
area. Data were available for 181 patients not previously known to have coeliac
disease, of whom 20 (11%) had EmA. All EmA-positive patients were referred to
hospital, where 19 underwent small-bowel biopsy, which confirmed coeliac disease
in all 19. Only 7 (35%) of the 20 had diarrhoea, and there was no significant
difference in EmA prevalence among patients tested with and without diarrhoea.
Although the mean number of new patients (per 100,000 population annually)
diagnosed by biopsy was 11 at the large hospital compared with 5 elsewhere, the
numbers identified by EmA in general practice for the 2 catchment areas were
similar (2 and 3, respectively). CONCLUSION: General practitioners have an
important role in the identification of patients with coeliac disease,
particularly where there is no local medical gastroenterology facility, and this
is facilitated by EmA testing.
PMID- 9648988
TI - Celiac disease risk in the USA: high prevalence of antiendomysium antibodies in
healthy blood donors.
AB - BACKGROUND: Recent epidemiologic studies in Europe using antigliadin (AGA) and
anti-endomysium antibodies (AEA) for initial screening have shown that the
overall prevalence of celiac disease (CD) is about 1:300. There are no comparable
scientific data for the USA, where CD is considered rare. The main aim of this
study was to determine the prevalence of increased AEA in healthy blood donors in
the USA. METHODS: Sera from 2000 healthy blood donors were screened for IgG AGA
and IgA AGA with an enzyme-linked immunosorbent assay test. All those with
increased AGA levels, those with intermediate levels, and random samples with low
levels were tested for AEA, using both monkey esophagus (ME) and human umbilical
cord (HUC) cryosections as substrates. RESULTS: The mean age of the blood donors
was 39 years, with 52% being men, 85.2% being Caucasian, 11.8% African-American,
1.5% Asian, and 1.5% Hispanic. Eight healthy blood donors had positive AEA tests
on both monkey esophagus and human umbilical cord. Among the eight subjects with
increased AEA levels seven were Caucasian and one was African-American. All the
four examined AEA-positive donors carried the known susceptibility alleles for
CD. CONCLUSIONS: The prevalence of increased AEA levels in healthy blood donors
in the USA is 1:250 (8:2000). This is similar to that reported in countries in
Europe, where subsequent small-intestinal biopsies have confirmed CD in all those
with AEA positivity. On the basis of a high positive predictive value of the AEA
antibody test, it is likely that the eight blood donors identified in this study
have CD. These data suggest that CD is not rare in the USA and that there is need
for a large-scale epidemiologic study to determine the precise prevalence of the
disease in the USA.
PMID- 9648989
TI - Dietary intake, smoking, and transient anti-gliadin antibodies.
AB - BACKGROUND: The detection of IgA anti-gliadin antibodies in adults can either be
helpful in the diagnosis of coeliac disease, be persistent in subjects with
normal jejunal mucosa, or occur transiently. We decided to investigate the
effects of smoking, alcohol consumption, and dietary intake on the development of
IgA anti-gliadin antibodies. METHODS: Serum samples from subjects enrolled from a
large Northern Ireland population sample (MONICA survey) were screened for IgA
anti-endomysium and IgA anti-gliadin antibodies. All subjects with positive
antibodies were invited for clinical assessment 3-4 years after the initial
screening sample. During this follow-up a repeat serum sample was obtained and a
jejunal biopsy performed. At enrollment in the MONICA survey, lifestyle
information including smoking, alcohol consumption, and dietary intake was
obtained. RESULTS: At follow-up 13 subjects had persistent positive serology and
villous atrophy, and 9 had persistent positive serology but normal jejunal
histology; in 29 the serology had returned to normal, and the jejunal histology
was normal There was no difference in smoking, alcohol consumption, or dietary
intake between subjects with and without coeliac disease. Subjects with transient
serology findings ate significantly more soda bread than the other groups (at the
time of initial screening). Analysis of gliadin content of soda bread and plain
white bread showed a significantly higher amount of gliadin present in soda
bread. CONCLUSIONS: Subjects with transient IgA anti-gliadin antibodies eat
significantly more soda bread. The gliadin content of Irish soda bread contained
a greater amount of gliadin than white bread. Eating breads with high available
gliadin content may cause the appearance of anti-gliadin antibody.
PMID- 9648990
TI - Increased serum levels of vascular endothelial growth factor in patients with
inflammatory bowel disease.
AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic,
vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine
with overexpression in various pathologic disorders, including granulomatous
inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid
arthritis, and tissue ischemia. The present study investigates the role of VEGF
in chronic inflammatory bowel disease. METHODS: Thirty-one patients with Crohn's
disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were
studied. VEGF serum levels were measured with a solid-phase enzyme-linked
immunosorbent assay. RESULTS: Significantly increased VEGF serum levels were
observed in both active Crohn's disease and active ulcerative colitis when
compared with healthy controls. Patients with active Crohn's disease and active
ulcerative colitis showed significantly higher VEGF serum levels than patients
with quiescent disease. No difference was observed between inactive disease and
healthy controls. In addition, strongly increased VEGF serum levels were found in
patients with Crohn's disease with fistulas in the absence of clinical,
endoscopic, histologic, and laboratory findings of disease activity. CONCLUSIONS:
Significantly increased VEGF serum levels were observed in patients with active
Crohn's disease and ulcerative colitis, which suggests that VEGF has an important
role in chronic inflammatory bowel disease. Its possible association with
fistulas has yet to be determined.
PMID- 9648991
TI - Perinuclear anti-neutrophil cytoplasmic antibodies in ulcerative colitis after
restorative proctocolectomy do not correlate with the presence of pouchitis.
AB - BACKGROUND: Although perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA)
expression is strongly associated with ulcerative colitis, its relationship with
the occurrence of pouchitis after restorative proctocolectomy is uncertain.
METHODS: Serum p-ANCA was assayed using both indirect immunofluorescence and
enzyme-linked immunosorbent assay (ELISA) in 49 patients, of whom 25 had, and 24
had not, developed pouchitis. Control sera were obtained from 15 healthy
volunteers. RESULTS: By means of indirect immunofluorescence, p-ANCA was detected
in 45.8% of patients without and in 48% with pouchitis (NS). Twenty-three (46.9%)
of the 49 colitis patients were p-ANCA-positive, compared with none of the 15
controls (P < 0.01). By means of ELISA, p-ANCA positivity was present in 50% of
patients without and in 68% with pouchitis (NS). CONCLUSION: Whereas p-ANCA was
associated with ulcerative colitis as compared with normal individuals, it was
not associated with pouchitis. Thus it is unlikely to be a suitable pre-operative
marker to identify those patients who will develop pouchitis.
PMID- 9648992
TI - The value of methods to determine zinc deficiency in patients with Crohn's
disease.
AB - BACKGROUND: The serum zinc concentration is frequently applied for the assessment
of zinc deficiency, but this concentration is also influenced by other factors.
The aim of this study was to compare various methods of assessing the zinc status
in patients with Crohn' s disease. METHODS: Serum levels of zinc, serum alkaline
phosphatase activity, and zinc in various types of cells were related to factors
potentially inducing zinc deficiency: the number of liquid stools, weight loss,
bowel resection, and the extent and severity of inflammation. RESULTS: Thirty-one
patients with more or less active Crohn's disease were included. In 68% of these
patients the serum zinc concentration was less than the reference level, and it
was correlated with the extent of bowel resection and the van Hees Index but not
with the Crohn's Disease Activity Index. Serum alkaline phosphatase activity was
correlated with bowel resection. Zinc in blood cells was poorly correlated with
factors inducing zinc deficiency. CONCLUSION: A decrease of serum zinc
concentration is frequently seen in active Crohn's disease. This study suggests
that the determination of zinc in blood cells is not superior to the
determination of the serum zinc concentration and serum alkaline phosphatase
activity.
PMID- 9648993
TI - Antineutrophil and pancreatic autoantibodies in first-degree relatives of
patients with inflammatory bowel disease.
AB - BACKGROUND: Perinuclear antineutrophil antibodies (P-ANCA) are found in
ulcerative colitis, and autoantibodies against exocrine pancreas (PAB) in Crohn's
disease. Their potential role as genetic or pathophysiologic factors is unclear.
METHODS: In 61 patients with ulcerative colitis, 76 patients with Crohn's
disease, 101 first-degree relatives of patients with ulcerative colitis, 105
first-degree relatives of Crohn's disease patients, and 56 healthy unrelated
controls autoantibodies were detected by indirect immunofluorescence. RESULTS:
Forty-six per cent of patients with ulcerative colitis (28 of 61) and 38% of
patients with Crohn's disease (29 of 76) were P-ANCA- and PAB-positive,
respectively. In relatives of patients with ulcerative colitis P-ANCA were found
in 3% (3 of 101), and in relatives of Crohn's disease patients PAB were detected
in 4% (4 of 105), which is not significantly different from the occurrence in the
healthy controls. CONCLUSIONS: The frequency of P-ANCA and PAB does not suggest a
role as genetic markers for inflammatory bowel disease.
PMID- 9648994
TI - Escherichia coli and Proteus mirabilis inhibit the perinuclear but not the
circulating antineutrophil cytoplasmic antibody reaction.
AB - BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) are found
in 48%-83% of serum samples from patients with ulcerative colitis (UC). Their
pathogenic role and initiating stimuli are unknown. In contrast to patients with
vasculitides and ANCA reactivities, the antibodies in UC patients do not react
with myeloperoxidase (MPO) or proteinase 3 (PR3). The aim of the present study
was to investigate whether bacterial species of the intestinal tract and other
sources could interfere with P-ANCA in sera from patients with UC. METHODS:
Seventeen P-ANCA-positive and anti-MPO-negative serum samples from patients with
UC were tested with Escherichia coli 014 and Staphylococcus aureus Wood 46. Six
of these serum samples with different P-ANCA titres were selected to test further
the influence of 15 different gram-negative or gram-positive bacterial strains.
Six anti-MPO positive P-ANCA, 5 anti-PR3 positive C-ANCA, and 10 antinuclear
antibody (ANA)-positive serum samples were used as controls. The antineutrophil
cytoplasmic antibodies (ANCAs) were analysed by an indirect immunofluorescence
method (IIF) on ethanol-fixed neutrophils, and the ANAs were tested by IIF on HEp
2 cells or rat liver tissues. The bacteria used in the experiments were either
live or killed by formalin or glutaraldehyde fixation or heated at 80 degrees C
for 30 min. The test was first performed as a bacterial absorption test with
sedimented organisms and then at various temperatures with the supernatant from
suspension of live bacteria. RESULTS: Both MPO-positive and MPO-negative P-ANCA
reactivity was abolished by absorption of patient sera with live E. coli and
Proteus mirabilis but not with bacteria representing members of 10 other species,
suggesting that antibody reactivity was absorbed away. However, continued
experiments indicated that the inhibition of P-ANCA was not due to classic
antigen-antibody interactions but rather to decomposition of the antigenic
substrate of the neutrophils by factors present in the supernatants of live E.
coli and P. mirabilis. The activity of the supernatant was temperature-dependent,
with strong activity at room temperature and 37 degrees C, no activity at 0
degrees C, and abolished by mild heat treatment (56 degrees or 60 degrees C). No
activity was shown in the supernatants from bacteria treated with formaldehyde or
glutaraldehyde. CONCLUSIONS: Soluble material from live E. coli and P. mirabilis
has the capacity to decompose the antigenic substrate of neutrophils responsible
for both MPO-positive and MPO-negative P-ANCA, most probably brought about
through enzymatic activity. Anti PR3-positive C-ANCA were not affected, which
suggests substrate specificity of the proposed enzymatic activity.
PMID- 9648996
TI - Stomach leiomyosarcoma: secular trends in incidence and survival in Sweden, 1960
1989.
AB - BACKGROUND: This population-based study was undertaken to investigate the
epidemiology of stomach leiomyosarcoma (GIS tumors) and to study the prognosis in
affected patients. METHODS: The Swedish Cancer Registry was used to identify all
incident cases of stomach leiomyosarcoma from 1960 to 1989, and the Death
Registry and the Registry of Population Changes were used for follow-up. RESULTS:
The age-standardized incidence in men increased from 1.0 per 10(6 ) per year in
1960-69 to 1.8 per 10(6) per year in 1980-89. The corresponding rates in women
were 0.6 per 10(6) and 1.2 per 10(6), respectively. The relative 5-year survival
was 39.4% in men and 62.4% in women (P = 0.03). There was no statistically
significant improvement in 5-year relative survival during the study period.
CONCLUSION: The observed incidence of stomach leiomyosarcoma increased during the
study period, most likely due to improved diagnostic accuracy. The survival of
patients with this malignant tumor remained unchanged.
PMID- 9648995
TI - An immunohistochemical study of bcl-2 and p53 protein expression in pancreatic
carcinomas.
AB - BACKGROUND: Only a few articles have examined the relationship between bcl-2
expression and clinical findings or bcl-2 expression and p53 expression in
pancreatic carcinomas. METHODS: We investigated bcl-2 protein and p53 protein
expression by means of immunohistochemical methods. RESULTS: The immunostaining
for bcl-2 was positive in 16 (20%) of 81 cases of pancreatic carcinoma. There
were no significant correlations between bcl-2 expression and the age, gender,
region of sampling, or clinical stage of the patients. Bcl-2 protein was detected
more frequently in histologically high-grade pancreatic carcinomas (grade III,
31%; grade II, 14%; grade I, 0%); however, there was no significant difference in
prognosis between patients with and without bcl-2 protein expression.
Immunostaining for the p53 protein was positive in 45 (56%) of 81 cases of
pancreatic carcinoma. There was no significant correlation between bcl-2 protein
expression and p53 protein expression. CONCLUSION: Bcl-2 was often detected in
histologically high-grade pancreatic carcinomas, although there was no
significant correlation between bcl-2 expression and the prognosis.
PMID- 9648997
TI - Long-term results of percutaneous transhepatic biliary drainage for benign and
malignant bile duct strictures.
AB - BACKGROUND: Long-term percutaneous transhepatic biliary drainage (PTBD) is a
valid alternative to surgery in patients with benign or malignant bile duct
strictures in whom endoscopic drainage has failed. However, few data are
available on the long-term outcome with percutaneous drainage, specially when the
application of Yamakawa-type prostheses is considered. METHODS: During 1996, 48
patients who were either treated with primary PTBD insertion followed by PTBD
exchanges (n = 15) or who presented only for exchange of an earlier PTBD (n = 33)
were included in the study. Thirty-one patients had malignant strictures, and 17
had benign ones. The PTBD catheters were scheduled for exchange every 3 months or
earlier if signs and symptoms of obstruction or other problems were present. The
data were collected prospectively during each follow-up visit and included both
symptoms and the status and function of the PTBD at the time of exchange.
RESULTS: Although PTBD was highly effective in relieving jaundice (progression of
cholestasis was observed in only 2 cases), 73 of the 157 PTBD exchanges (47%) had
to be carried out earlier than scheduled. Premature exchange was needed for
clinical reasons, such as fever indicating PTBD dysfunction, in only 19% of these
cases. The other reasons were related to the PTBD catheter and consisted of bile
leakage alongside the drain (33%), PTBD disconnection or complete dislocation
(30%), or occlusion suspected during regular flushing of the drain (15%). In most
cases exchanging the drain was sufficient to solve the problem; in cases of
complete dislocation, dilation of the same tract (n = 6) or fresh puncture and
establishment of a new drainage site (n = 2) were necessary. Reducing the PTBD
exchange interval from 3 to 2 months would have decreased the number of premature
stent exchanges by 26%. CONCLUSIONS: Although PTBD is an effective method of
biliary drainage, there are frequently minor problems-mostly catheter-related
which require premature exchange of the drain in almost half of the cases, and
this may affect the patients' quality of life. Improvements in PTBD materials and
catheter design are therefore needed. The effectiveness of reducing the intervals
between PTBD exchanges should also be examined.
PMID- 9648998
TI - Neuroticism in relation to recovery and persisting pain after laparoscopic
cholecystectomy.
AB - BACKGROUND: Persisting pain is seen in 20%-30% of patients after cholecystectomy
for symptomatic gallbladder stones. The only preoperative factor that seems
predictive is psychic vulnerability or neuroticism. Findings with regard to the
influence of psychologic factors on recovery are contradictory, too. The aim of
the present study was to examine a possible relationship between neuroticism and
recovery and the outcome of operation. METHODS: Ninety-four patients who had had
a laparoscopic cholecystectomy performed were tested psychologically with a
Danish psychic vulnerability scale and with the Eysenck Neuroticism Scale before
and 1 year after operation. The course of recovery was registered 1 month after
operation, and outcome with regard to persisting pain 1 year postoperatively.
RESULTS: No correlations were found between neuroticism scores and postoperative
hospital stay or time to regain work/normal activities (P > 0.05). Persisting
pain was found in 18% of the patients 1 year after operation. Although the
patients with persisting pain had higher neuroticism scores preoperatively, the
difference from the patients with successful outcome of the operation first
became statistically significant 1 year postoperatively (P < 0.01-0.05).
CONCLUSIONS: The results do not indicate that neuroticism influences the short
recovery process after laparoscopic cholecystectomy. With regard to persisting
pain, the higher neuroticism scores in these patients 1 year after the operation
could be the consequence of the pain rather than aetiologic factors.
PMID- 9648999
TI - Value of early blood Th-1 cytokine determination in predicting severity of acute
pancreatitis.
AB - BACKGROUND: Early evaluation of the severity of acute pancreatitis (AP) requires
measurement of many variables within 48 h after admission. Septic complications
(SC) are frequent, and preliminary studies have highlighted the value of
prophylactic antibiotherapy; however, single and reliable predictive markers of
sepsis are not yet available. The aim of this study was to assess the value of
determining early blood Th-1 cytokines and their natural antagonists (interleukin
6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF)
receptors RI and RII) to predict the severity and SC during AP. METHODS: Thirty
seven patients with AP were prospectively included; 25 of them had severe AP,
including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset
of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC
diagnostic thresholds was determined using receiver operative curves. RESULTS:
Severe AP in accordance with the Atlanta criteria were better predicted by C
reactive protein and IL-6 serum determination, albeit these levels could not
predict absolutely the death of two patients. In severe AP cases (n = 25) the IL
1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(
3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus
2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P
< 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio
and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/
0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l,
P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3).
The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5
x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750
pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2
ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3). CONCLUSION: Besides severity
markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP
assays and, if confirmed by larger studies, could help to screen patients at risk
for SC and candidates for prophylactic antibiotherapy with a good negative
predictive value.
PMID- 9649000
TI - Reflections on Crohn's disease and healing.
AB - One patient's story is recounted. Relatively asymptomatic for 20 years, the
patient reflects on factors that contributed to his healing. Psychosocial and
spiritual dimensions are described as well as biomedical aspects. The story
concludes that dealing with Crohn's disease triggered a spiritual quest which in
turn contributed to the patient's healing.
PMID- 9649001
TI - Hot water swallows improve symptoms and accelerate esophageal clearance in
esophageal motility disorders.
AB - Cold liquid ingestion may precipitate episodes of dysphagia and chest pain in
patients with spastic esophageal motility disorders. The effect of hot liquids on
esophageal symptoms, esophageal peristalsis, and clearance and any potential
therapeutic benefit in such patients has not been examined. Using esophageal
scintigraphy and manometry, we have investigated the effects of hot water
swallows on dysphagia, chest pain, and esophageal motility and clearance in
patients with esophageal motility disorders. We studied 48 men and women with
intermittent dysphagia to both solids and liquids, chest pain, and/or
regurgitation. All patients underwent upper endoscopy, barium swallow, and
esophageal manometry using standard techniques. Esophageal scintigraphy assessed
esophageal transit time (ETT) and retrograde intraesophageal movement of bolus at
baseline (22 degrees C) and after hot (60 degrees C) water swallows. Esophageal
manometry assessed the amplitude and duration of esophageal contractions in
response to baseline and hot water swallows. Patients were followed clinically
for as long as 6 months to assess symptomatic response. We found that baseline
esophageal scintigraphy revealed a mean ETT of 48.5 seconds; after hot water
swallow, mean ETT was 27.8 seconds (p < 0.001). The number of secondary peaks at
baseline was 3.5; after hot water swallow, it was 2.1 (p < 0.001). Baseline
esophageal manometry showed a mean esophageal body contraction amplitude of 188
mm Hg (mean duration, 11.8 seconds) in response to wet swallows and 125 mm Hg
(mean duration, 5.7 seconds) with hot water swallows (p < 0.001). Clinically, 28
(58%) of 48 patients noted significant (>50%) improvement of their symptoms and
have been ingesting hot water or other hot liquids regularly with their meals. We
conclude that hot water accelerates esophageal clearance, decreases the amplitude
and duration of esophageal body contractions, and improves symptoms in patients
with esophageal motility disorders. Because of its safety and simplicity, it may
have an important role in the management of these chronic conditions.
PMID- 9649002
TI - Pulmonary nodules in patients with esophageal carcinoma.
AB - The clinical significance of lung nodules in patients with esophageal carcinoma
has received little attention. Therefore, we carried out a retrospective detailed
review of 116 consecutive cases of esophageal carcinoma, including 98 squamous
cell cancers, seen at the Philadelphia Veterans Affairs Medical Center between
1984 and 1997. Seventy-four percent of our patients were black; it was not
surprising therefore that 84% of our patients in this series had squamous cell
cancers. Initially, chest radiographs, computed tomography (CT) scans, or
thoracotomy showed solitary pulmonary nodules in 22 (19%) patients. A definitive
diagnosis was established in 19 patients, including 15 (68%) benign nodules and 4
(18%) new primary lung carcinomas. Three (14%) nodules were indeterminate, but in
no case could a solitary lung metastasis be identified. Radiographic evidence of
multiple lung metastases was present, however, in 4 (3%) of 116 patients at
diagnosis. Autopsies of six patients were later performed, and three showed
multiple lung metastases; two of these patients had negative chest radiographs
shortly before death. Our experience suggests that for a cohort of mostly
squamous cell esophageal cancers, a solitary lung metastasis is rare at
diagnosis; a solitary pulmonary nodule at this time likely represents a benign
abnormality or primary lung cancer. Multiple pulmonary metastases are also very
unusual at diagnosis, probably become increasingly common during the terminal
phases of disease, and may be radiographically occult.
PMID- 9649003
TI - In vivo comparison of esophageal varices at and above the diaphragmatic high
pressure zone using high resolution endoluminal sonography.
AB - Our objective in this study was to use high resolution endoluminal sonography to
compare the size of esophageal varices within 5 cm of and at the esophageal high
pressure zone. We carried out the study in 36 patients with endoscopically proven
esophageal varices. A 20-MHz 6.2F ultrasound catheter was passed through a 34F
endoscope and used to image esophageal varices as it was slowly withdrawn through
the high pressure zone (the level at which the diaphragm was imaged) and into the
body of the esophagus approximately 5 cm above the high pressure zone. All images
were captured on videotape and reviewed by one of the investigators. The mean,
total, and percent cross-sectional surface areas occupied by varices were
calculated and then compared within 5 cm and at the esophageal high pressure
zone. Six of 36 (17%) patients had no varices imaged at the high pressure zone
but did have varices imaged in the distal esophagus. The mean cross-sectional
surface area per varix at the high pressure zone (0.036+/-0.006 cm2) was
significantly less (p < or = 0.0001) than the mean cross-sectional area per varix
5 cm above the high pressure zone (0.142+/-0.018 cm2). The average total cross
sectional surface area occupied by varices at the high pressure zone (0.137+/
0.034 cm2) was significantly less (p < 0.0001) than the average cross-sectional
surface area occupied by varices 5 cm above the high pressure zone (0.672+/-0.080
cm2). The mean percent esophageal wall cross-sectional surface area occupied by
varices at the high pressure zone (16%) was significantly less (p < or = 0.0001)
than 5 cm above the high pressure zone (49%). We conclude that the mean, total,
and percent cross-sectional surface areas of esophageal varices at the high
pressure zone are significantly less than those 5 cm above the high pressure
zone.
PMID- 9649004
TI - Factors affecting patient tolerance of upper gastrointestinal endoscopy.
AB - Doctors are optimistic in their perception of how acceptable endoscopy is for
patients. We analyzed elements that contribute to a poor experience for the
patient and the agreement between the perceptions of endoscopists and patients.
Eighty-four out-patients who had undergone gastroscopy completed questionnaires
(response rate of 73%) 48 to 96 hours after the procedure. The endoscopist
completed a similar questionnaire. Questions concerned overall tolerance,
swallowing, retching and vomiting, sedation, duration, diagnosis, age, and sex.
Data from both doctor and patient were available in 84 cases. The type of
sedation, administration of hyoscine or Xylocaine (Astra Pharmaceuticals Ltd.,
Kings Langley, UK), diagnosis, and expression of need for more sedation were not
statistically significantly related to the overall patient score. The largest
contribution to a poor overall tolerance score arose from difficulty in
swallowing the endoscope, followed by the duration of the procedure. A total of
8.3% of patients reported some overall difficulty which was not recognized by the
endoscopist. In relation to retching and vomiting, 11.9% of patients had
difficulty with retching and vomiting, which went unrecognized by the doctor, and
18% had difficulty in swallowing the endoscope. There was fair agreement between
the assessments of overall acceptability of both endoscopists and patients.
Difficulty in intubation, however, is the major contributor to a poor tolerance
of gastroscopy and also the issue on which doctors and patients disagreed the
most.
PMID- 9649005
TI - Ambience in the endoscopy room has little effect on patients.
AB - With hopes of alleviating discomfort and improving the tolerance of patients
undergoing endoscopy, we have assessed the influence of various background
conditions in the endoscopy room. Two hundred twenty-one candidates for upper
endoscopy were randomly allocated to four groups, each with one of the following
conditions in the endoscopy room: background music and conversation related to
the patient's complaints (n=50); background music and conversation unrelated to
the patient (n=53); background music only, with the staff maintaining silence
(n=49); and complete silence (n=47). Before endoscopy patients answered a 26-item
questionnaire that included an evaluation of their degree of anxiety before the
examination. Conscious sedation was induced by using 3 mg midazolam. After
complete recovery from sedation, patients answered another set of questions.
Patients in all four groups felt quite comfortable with the atmosphere in which
gastroscopy was performed. Neither music, conversation, nor silence had a great
effect on patients as far as improving tolerance or diminishing anxiety.
Therefore, endoscopists and nurses may have a free hand in choosing the
prevailing conditions during the examination. This conclusion may be valid for
both patients and the staff involved in other invasive procedures performed under
light sedation.
PMID- 9649006
TI - Helicobacter pylori infection is markedly increased in patients with autoimmune
atrophic thyroiditis.
AB - Infection by viral or bacterial pathogens has been suspected in playing a role in
the development of autoimmune thyroid disease. Because Helicobacter pylori might
be involved in the development of nongastrointestinal conditions such as rosacea,
ischemic heart disease, and diabetes mellitus, we evaluated the prevalence of H.
pylori infection in patients with autoimmune thyroid disease. Fifty-nine patients
with autoimmune thyroid disease were included: autoimmune atrophic thyroiditis
(n=21), Hashimoto's thyroiditis (n=18), and Graves' disease (n=20). Twenty
patients with nontoxic multinodular goiter served as controls for nonautoimmune
thyroid disease, and 11 patients with Addison's disease served as controls for
nonthyroid endocrine autoimmune disease. The levels of anti-H. pylori
immunoglobulin G (IgG) were determined, and a radiolabeled urea breath test were
performed. The prevalence of H. pylori infection was markedly increased in the
patients with autoimmune atrophic thyroiditis (85.7%), compared with the controls
with nontoxic multinodular goiter (40%) and Addison's disease (45.4%). Infection
by H. pylori resulted in increased levels of gastrin, pepsinogen I, and
pepsinogen II in the H. pylori-positive groups, compared with the H. pylori
negative groups. A positive linear regression was found between the levels of
microsomal autoantibodies and those of anti-H. pylori IgG in patients with
autoimmune atrophic thyroiditis (n=21; r=0.79; p < 0.01). Finally, and although
the overall prevalence of H. pylori infection was not increased, the anti-H.
pylori IgG levels and the results from the breath test were higher in the
patients with Graves' disease and Hashimoto's thyroiditis patients than in the
controls. Clearly, the prevalence of H. pylori infection is increased in
autoimmune atrophic thyroiditis and results in abnormalities of gastric secretory
function. The strong relation between the levels of anti-H. pylori IgG and the
levels of microsomal antibodies suggests that H. pylori antigens might be
involved in the development of autoimmune atrophic thyroiditis or that autoimmune
function in autoimmune atrophic thyroiditis may increase the likelihood of H.
pylori infection.
PMID- 9649007
TI - A simplified urea breath test for the diagnosis of Helicobacter pylori infection
using the LARA System. Laser Assisted Ratio Analyzer.
AB - Helicobacter pylori, one of the most prevalent human pathogens, is associated
with chronic gastritis, peptic ulcer disease, and possibly gastric cancer and
primary gastric lymphoma. The need to treat these patients has necessitated the
development of improved methods to diagnose H. pylori infection. We present the
preliminary assessment of a 13C-urea breath test (UBT) in which the expired 13CO2
is detected in a rapid, simple, inexpensive way by the LARA (Laser Assisted Ratio
Analyzer) System (Alimenterics, Inc., Morris Plains, NJ). Eighty-seven
consecutive patients, examined for upper gastrointestinal symptoms, underwent
endoscopy. H. pylori infection was established by antral biopsies and a rapid
urease test (CLOtest). The UBT was performed between 2 and 24 hours after
endoscopy. Of the 84 analyzable patients, 70 were found to be H. pylori-positive
either by histology or by CLOtest. All 70 were positive by the LARA UBT, yielding
a sensitivity of 100%. Fourteen patients were negative for H. pylori by histology
and the CLOtest. Of these, 12 were negative by the LARA UBT and 2 were positive,
yielding a specificity of 85.7%; because of the limitations of H. pylori
detection by histology or urease assays, however, the specificity of the UBT may
have been underestimated. Our study demonstrates the feasibility of a
nonradioactive, rapid UBT based on the LARA system and suggests the need for its
more detailed evaluation.
PMID- 9649008
TI - Premedication with Xylocaine spray does not lead to a false positive rapid urease
test.
AB - Rapid urease tests are used for quick identification of Helicobacter pylori
during upper gastrointestinal endoscopy. Rapid urease test solutions contain
urea, which in the presence of H. pylori urease, generates ammonia, which changes
the test medium color to indicate a positive result. Theoretically, Xylocaine
spray (ASTRA, Sodertalje, Sweden), which has a basic pH value, could cause a
similar positive reaction in the test medium. To determine whether patients
premedicated with Xylocaine spray have a higher rate of false positive urease
tests, we compared the results of a rapid urease test and histologic stains in
107 patients, 54 premedicated with Xylocaine spray and 53 premedicated with
intravenous midazolam but not Xylocaine spray. There were no significant
differences in test sensitivity, specificity, or predictive values between the
study groups. We conclude that patients can be premedicated with Xylocaine spray
without concern that the false positive rate of rapid urease tests will increase.
PMID- 9649009
TI - Postoperative chemotherapy may improve prognosis in unresectable gastric cancer.
AB - We have retrospectively evaluated to prognosis of patients with unresectable
gastric cancer (UGC) and the effect of postoperative chemotherapy on that
prognosis. One hundred patients who died of UGC included 37 patients who received
postoperative chemotherapy (chemotherapy group) and 63 patients who did not
receive postoperative chemotherapy (control group). Chemotherapy regimens were as
follows: intravenous mitomycin (MMC) plus 5-fluorouracil (5-FU) (n=15), oral 5-FU
alone (n=10), intravenous methotrexate (MTX) plus 5-FU (n=8), intravenous
cisplatin plus 5-FU (n=2), and hepatic arterial infusion of 5-FU plus oral 5-FU
(n=2). No prior chemotherapy or radiation therapy was given. All patients'
cancers were stage IV. Median survival of the chemotherapy group (238 days) was
significantly longer than the control group (137 days). The 1-year survival rate
in the treated group was 19.0% but only 2.4% in the control group (p < 0.01).
Patients with palliative gastrojejunostomy did not survive significantly longer
than those having laparotomy alone or ileal tube insertion. We conclude that the
prognosis for patients with UGC remains very poor, but postoperative chemotherapy
may contribute to prolonged survival in patients with UGC.
PMID- 9649010
TI - Relatively low expression of multidrug resistance-1 (MDR-1) and its possible
clinical implication in gastric cancers.
AB - The mechanism of drug resistance of gastric cancer cells has rarely been
investigated. We specifically examine the magnitude and the biologic significance
of multidrug resistance-1 (MDR-1) expression in human gastric cancer. All
patients had previously been treated in prospective clinical trials for advanced
gastric cancer in our institution. Patients with adequate prechemotherapy gastric
cancer tissues for immunohistochemical studies by a C219 monoclonal antibody were
selected for the determination of the expression rate of MDR-1. The results were
designated as negative or positive by the independent interpretation of two
pathologists. A subgroup of patients who had been treated with doxorubicin- or
etoposide-containing regimens were selected for further correlation with drug
sensitivity. Between 1990 and 1996, a total of 60 patients, 38 men and 22 women
with a median age of 55 years, were studied. Eight (13.3%; 95% confidence
interval, 6%-25%) of them had MDR-1 expression. None of the pertinent
clinicopathologic features, including the histopathologic types of the tumors and
the extent of the diseases, correlated with the expression of MDR-1. Among the 30
patients who had received doxorubicin- or etoposide-containing combination
chemotherapy, 3 (10%; 95% confidence interval, 3%-27%) were designated positive
for MDR-1 expression. None of the 3 patients responded to chemotherapy, whereas
19 (70.4%) of the 27 patients who had not expressed MDR-1 did respond (p=0.041 by
Fisher's exact test). We conclude that the expression of MDR-1 in gastric cancer
is relatively low. Its expression, however, is clinically relevant and is useful
in predicting the chemoresistance of patients with gastric cancer receiving
doxorubicin- or etoposide-containing combination chemotherapy.
PMID- 9649011
TI - Colonoscopy without sedation.
AB - Colonoscopy is routinely performed with conscious sedation. We wanted to
determine if colonoscopy can be successfully completed without sedation and to
assess patient tolerance and acceptance. One hundred nine consecutive patients
undergoing colonoscopy were examined. The risks and benefits of colonoscopy with
or without sedation were explained in a standard format. Patients were then given
the option of having colonoscopy without premedication. After the procedure, as
well as 2 to 5 days later, patients rated on an analog scale (0, no pain; 5,
severe) the severity of pain and willingness to undergo colonoscopy in the future
without sedation. Eighty patients underwent colonoscopy without prior sedation.
Only 6% (n=5) required sedation to complete the examination. When questioned, 5%
experienced no pain, 41% slight or mild pain, 34% moderate pain, and 20% severe
pain. Seventy-three percent (n=58) were willing to undergo repeat colonoscopy
without sedation, 10% (n=8) were undecided, and 18% (n=14) would request
sedation. Pain severity was a strong predictor (p=0.001) of future sedation
preference. Colonoscopy without sedation may be completed successfully in most
patients and does not undermine many patients' willingness to undergo a similar
procedure in the future. Sedation by choice is more cost-effective, may be safer,
and should be offered as an alternative to routine intravenous sedation.
PMID- 9649012
TI - Alterations in colonic anatomy induced by chronic stimulant laxatives: the
cathartic colon revisited.
AB - Cathartic colon is a historic term for the anatomic alteration of the colon
secondary to chronic stimulant laxative use. Because some have questioned whether
this is a real entity, we investigated changes occurring on barium enema in
patients ingesting stimulant laxatives. Our study consisted of two parts. In part
1, a retrospective review of consecutive barium enemas performed on two groups of
patients with chronic constipation (group 1, stimulant laxative use [n=29]; group
2, no stimulant laxative use [n=26]) was presented to a radiologist who was
blinded to the patient group. A data sheet containing classic descriptions of
cathartic colon was completed for each study. Chronic stimulant laxative use was
defined as stimulant laxative ingestion more than three times per week for 1 year
or longer. To confirm the findings of the retrospective study, 18 consecutive
patients who were chronic stimulant laxative users underwent barium enema
examination, and data sheets for cathartic colon were completed by another
radiologist (part 2). Colonic redundancy (group 1, 34.5%; group 2, 19.2%) and
dilatation (group 1, 44.8%; group 2, 23.1%) were frequent radiographic findings
in both patient groups and were not significantly different in the two groups.
Loss of haustral folds, however, was a common finding in group 1 (27.6%) but was
not seen in group 2 (p < 0.005). Loss of haustral markings occurred in 15 (40.5%)
of the total stimulant laxative users in the two parts of the study and was seen
in the left colon of 6 (40%) patients, in the right colon of 2 (13.3%) patients,
in the transverse colon of 5 (33.3%) patients, and in the entire colon of 2
(13.3%) patients. Loss of haustra was seen in patients chronically ingesting
bisacodyl, phenolpthalein, senna, and casanthranol. We conclude that long-term
stimulant laxative use results in anatomic changes in the colon characterized by
loss of haustral folds, a finding that suggests neuronal injury or damage to
colonic longitudinal musculature caused by these agents.
PMID- 9649014
TI - Abnormal liver test results in myotonic dystrophy.
AB - Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder. Little
evidence suggests the existence of liver damage in a small number of patients. We
have prospectively evaluated liver and gallbladder function in 53 patients with
DM in relation to clinical and genetic parameters. None of the patients had an
enlarged liver, signs of cirrhosis, or portal hypertension. All were free of
medication, and none were pregnant or had a history of alcohol abuse. In 35 (66%)
patients, serum activity of at least one of six liver enzymes assayed was
abnormal. An elevated level of alkaline phosphatase was found in 50.9%, of gamma
glutamyltransferase in 52.8%, of 5' nucleotidase in 43.4%, of serum aspartate
aminotransferase in 35.8%, of serum alanine aminotransferase in 33.9%, and of
lactate dehydrogenase in 37.7%. Liver function test results did not correlate
with severity of muscle weakness, disease duration, or serum levels of creatine
kinase, glucose, or lipids. Motility of gallbladder and abdominal ultrasonography
were normal. Cytosine-thymidine-guanine repeat expansion by southern blot did not
correlate with liver enzyme abnormalities. We conclude that elevation of liver
enzymes is frequent in DM and should be included as an additional laboratory
finding of the disease.
PMID- 9649013
TI - A combination therapy with simvastatin and ursodeoxycholic acid is more effective
for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.
AB - Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been
reported to decrease the cholesterol saturation index (CSI) in duodenal bile in
humans and to prevent formation of cholesterol gallstones in animal studies. We
performed a prospective study to evaluate the role of HMG-CoA reductase
inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent
gallstones in a gallbladder opacifying at drip infusion cholecystography were
treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid
(group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12
months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid
levels were assessed and ultrasonographic examination of the gallbladder was
performed at baseline and at 3-month intervals during treatment. Duodenal bile
sampling was performed in five patients in each group at baseline and after 12
months of treatment. Plasma cholesterol decreased significantly in group 1 but
not in group 2. In solitary gallstone cases, no significant difference in
dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12,
33%). In contrast, the dissolution rate in multiple gallstone cases was
significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p
< 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01)
but did not significantly differ between the two groups. These results suggest
that combination therapy with simvastatin and ursodeoxycholic acid is more
effective for cholesterol gallstone dissolution than ursodeoxycholic acid
monotherapy in patients with multiple gallstones.
PMID- 9649015
TI - Influence of pretreatment lesions on histologic response to interferon therapy in
chronic hepatitis C.
AB - We have assessed the predictive value of the grade of pretreatment liver lesions
on histologic response to interferon therapy in patients with chronic hepatitis
C. In 93 patients with chronic hepatitis C virus (HCV) infection who showed an
initial response to interferon therapy, HCV RNA load and serum aminotransferase
levels together with grade of liver histologic lesions were assessed at baseline
and 6 months after treatment cessation. Regression of portal and periportal
necroinflammation was observed only in sustained responders (normalization of
aminotransferase levels and HCV RNA clearance). Neither short-term response nor
the absence of virus was associated with significant histologic changes in the
liver biopsies. Logistic regression analysis showed that pretreatment histologic
lesion was an independent predictive factor of biologic response in the
histologic regression of lesions 6 months after cessation of interferon
treatment. In conclusion, a dense inflammatory necrotic activity is a positive
predictor of histologic response in interferon-treated patients with HCV.
PMID- 9649016
TI - Chronic diarrhea--induced by celiac plexus block?
AB - A 59-year-old man had severe chronic diarrhea after a celiac plexus block. The
block was performed because of unbearable abdominal pain caused by a benign cyst
in the lesser sac. The patient also had diabetes mellitus and was treated with
metformin. Thorough investigation and various therapeutic trials failed to detect
the cause for the diarrhea or to improve it. Based on the temporal relationship
we wonder whether the diarrhea was induced by the celiac block procedure. The
relevant literature is reviewed.
PMID- 9649017
TI - Idiopathic portal hypertension and angiosarcoma associated with arsenical salts
therapy.
AB - We describe a 60-year-old man with idiopathic portal hypertension and hepatic
angiosarcoma. The patient had taken an arsenical preparation for the treatment of
psoriasis for 10 years. Five cases of this association have been reported
previously; in one only, exposure to arsenical salts was present.
PMID- 9649018
TI - Serious hemorrhage complicating diagnostic abdominal paracentesis.
AB - We describe two patients awaiting orthoptic liver transplantation in whom
diagnostic paracentesis for the diagnosis of spontaneous bacterial peritonitis
led to major hemorrhage. Accordingly, we advise caution in patients such as ours,
particularly if the prothrombin time or partial thromboplastin time is more than
twice the control value.
PMID- 9649019
TI - Cystic lymphangioma of the spleen mimicking hydatid disease.
AB - Cystic lymphangioma is a very rare condition generally accepted to be the result
of a developmental malformation of the lymphatic system. Usually seen in
children, it occurs infrequently in adults. The neck (75%) and axillary regions
(20%) are the most common locations of lymphangioma, but it can occur in the
retroperitoneum, mediastinum, mesentery, omentum, colon, pelvis, groin, bone,
skin, scrotum, and spleen. We present a cystic lymphangioma of the spleen with
emphasis on its rarity in this site and problems of differential diagnosis with
hydatid disease.
PMID- 9649020
TI - Meta-analysis of antisecretory and gastrokinetic compounds in functional
dyspepsia.
AB - In view of therapeutic advances, we carried out meta-analysis of results from 18
randomized, controlled clinical studies to update a previous meta-analysis and to
provide an overview of clinical trials involving treatment of functional
dyspepsia. The studies were included only if they satisfied inclusion and
exclusion criteria and assessed treatment of functional dyspepsia with the
antisecretory compounds cimetidine and ranitidine and the gastrokinetic compounds
cisapride and domperidone. Outcomes of each of these trials were classified in
terms of differences in therapeutic success between active treatment and placebo.
For antisecretory treatments, the 95% confidence intervals for the difference in
therapeutic success between active treatment and placebo were inconsistent for
cimetidine, but analysis of both ranitidine trials gave favorable results. For
the gastrokinetic compounds cisapride and domperidone, the differences in success
rates were generally higher and more in favor of active treatment than placebo.
By combining the results from both antisecretory treatments and comparing them
with the combined results for gastrokinetic compounds, we observed that
gastrokinetic compounds had a greater difference in success rates than did
antisecretory agents. Overall, our meta-analysis shows that antisecretory
treatment with cimetidine or ranitidine offers little advantage over placebo,
whereas gastrokinetic treatment with cisapride or domperidone is significantly
better than placebo for treatment of functional dyspepsia.
PMID- 9649021
TI - The chewable barium tablet slow tracking of oral and pharyngeal swallowing
dysfunction.
AB - Dysphagia can be due to oral or pharyngeal dysfunction as well as to esophageal
causes. Oral and pharyngeal disturbances, however, are more common in older
people because of their attendant risks of laryngeal, tracheal, and pulmonary
aspiration. To guide any dietary prescriptions it is important to establish
whether the patient can best tolerate liquids, soft foods, solid chewable
boluses, all, or none of these. It therefore becomes important to supplement
liquid barium swallowing studies with soft and chewable boluses mixed with
barium. Here I describe the novel introduction of chewable barium tablets in
conjunction with routine swallowing studies. Chewable barium tablets, if used
properly, are safe, supply needed information, and can shorten the evaluation of
oral and pharyngeal dysfunction studies. Because of the granular appearance of
the tablets, aspiration due to this solid chewable bolus can be distinguished
from liquid aspiration. Moreover, if the barium tablets are swallowed whole, they
can help delineate esophageal strictures if the oral and pharyngeal phases of
swallowing are normal.
PMID- 9649022
TI - The histopathology and biologic prognostic factors of Barrett's esophagus: a
review.
AB - In Barrett's esophagus, stratified squamous mucosa of the lower third of the
esophagus is replaced by columnar mucosa, as a complication of chronic
gastroesophageal reflux. The presence of Barrett's esophagus appears to be a
major factor in the progression to adenocarcinoma of the lower third of the
esophagus. Therefore it is crucial to identify the subset of patients at risk for
the development of adenocarcinoma. Dysplasia is an important histologic feature
to evaluate because it identifies those patients who require follow-up. The
diagnosis of biopsies with lesser degrees of abnormalities, however, makes
microscopic evaluation less helpful in identifying patients who need more
frequent endoscopic biopsy surveillance. DNA ploidy and the use of monoclonal
antibodies, such as suppressor gene product p53, oncogene cerbB-2, and Ki-67,
have added dramatically to our understanding of the biology of Barrett's
metaplasia and have given us objective indicators to predict the presence of an
increased risk of developing cancer.
PMID- 9649023
TI - Extreme right lobar atrophy of the liver: a rare complication of autoimmune
hepatitis.
AB - Lobar atrophy is a rare morphologic change of the liver. We describe a 73-year
old woman with mild liver dysfunction and history of Sjogren's syndrome who had
right hepatic lobar atrophy. Serum biochemistry levels were as follows: albumin,
4.5 g/dl; total bilirubin, 1.0 mg/dl; alanine aminotransferase, 25 international
units/l; aspartate aminotransferase, 27 international units/l; alkaline
phosphatase, 333 international units/l; and gamma-glutamyl transpeptidase, 332
international units/l. Serological data were as follows: rheumatoid factor, 27.9;
anti-nuclear antibody, 1:640; and antismooth muscle antibody, 1:80. Viral markers
for hepatitis B were all negative. Anti-hepatitis C virus (anti-c-100) was
negative. Portal hypertension developed thereafter, and the patient died of
hepatic failure at age 76. Postmortem examination revealed autoimmune hepatitis
with moderate fibrosis, portal vein thrombus, and complete obstruction of the
right hepatic duct due to hepatolithiasis. Terminal hepatic failure resulted from
combination of decreased hepatic volume due to the right lobar atrophy,
exacerbation of autoimmune hepatitis in the remnant left hepatic lobe, decreased
portal venous blood flow due to thrombosis, portal hypertension, and cholangitis
with hepatolithiasis. This is the first reported case of hepatic lobar atrophy
due to autoimmune hepatitis. From a clinical standpoint, patients with hepatic
lobar atrophy, even if asymptomatic, should be followed up with careful attention
to progression of liver diseases, portal hypertension, and biliary complications.
PMID- 9649024
TI - Enteropathy-associated T cell lymphoma with brain involvement.
AB - In a patient with enteropathy-associated T cell lymphoma. there was dissemination
to the brain manifesting as an inflammatory lesion. the intestinal and brain
lesions were studied using routine histology, immunohistochemistry, and
polymerase chain reaction. The jejunum was involved by a multifocal large cell
lymphoma associated with multiple inflammatory ulcers and villous atrophy with
crypt hyperplasia of the intervening mucosa. The lesion in the brain consisted of
necrotic tissue associated with an infiltrate of histiocytes and a relatively
scant infiltrate of primarily small lymphocytes. The appearance was that of an
inflammatory rather than a neoplastic process. The intestinal lymphoma cells were
positive for T cell markers and contained cytotoxic granules detected with the
TIA-1 monoclonal antibody. The small lymphocytes and occasional large cells in
the cerebral lesion showed the same immunophenotype. DNA extracted from the
intestinal lymphoma and the cerebral lesion showed identical monoclonal
rearrangement of the TCR-gamma gene. Dissemination from enteropathy-associated T
cell lymphoma may masquerade as an inflammatory lesion. Molecular analysis is
useful in confirming the diagnosis.
PMID- 9649025
TI - Telephone callback is unnecessary after outpatient endoscopy.
PMID- 9649026
TI - Nonsteroidal anti-inflammatory drugs and gastrocolic fistula.
PMID- 9649027
TI - Unsuccessful octreotide treatment of the watermelon stomach.
PMID- 9649028
TI - Colon cancer after Bowen's disease.
PMID- 9649029
TI - Colonic metastasis of a lung carcinoma with ileocolic fistula.
PMID- 9649030
TI - Endosonographic probe-guided endoscopic resection of focal lymphoid hyperplasia
of the rectum.
PMID- 9649031
TI - Intramural duodenal hematoma due to pancreatitis.
PMID- 9649032
TI - Two patients with portal vein thrombosis from lupus anticoagulant.
PMID- 9649033
TI - Mixed adenocarcinoid tumor and Crohn's disease.
PMID- 9649034
TI - Amebic abscess of the caudate lobe with spontaneous rupture into the biliary
tract.
PMID- 9649035
TI - Duodenal stenosis does regress after eradication of Helicobacter pylori!
PMID- 9649036
TI - Short-segment Barrett's esophagus.
PMID- 9649037
TI - Totally laparoscopic aortobifemoral bypass: a review of 10 patients.
AB - The main purpose of this study is to evaluate the feasibility of totally
laparoscopic aortobifemoral bypass for occlusive aortoiliac disease. Ten patients
who had incapacitating claudication have been included to date in this
investigation. We have designed a transabdominal retroperitoneal technique that
allows performance of the procedure without the problems associated with
retraction of intraperitoneal organs. During the study, surgery time decreased
from 510 to 245 min. Mean total aortic clamping time was 121 min, and the mean
time required to perform the aortic anastomosis was 66 min. Mean blood loss was
820 ml. Three patients needed conversion. Postoperative complications developed
in three patients. One had an aortoureteral fistula, which needed reoperation;
one experienced complications related to a retroaortic left renal vein; and the
third had a mild compartment syndrome of the right leg. Totally laparoscopic
aortobifemoral bypass is feasible. Laparoscopic aortobifemoral bypass appears to
ease the patient's postoperative course and could become in the not so distant
future part of the repertoire of the surgeon performing vascular surgery.
PMID- 9649038
TI - Technical aspects of minimally invasive abdominal surgery performed with
needlescopic instruments.
AB - Interest has grown in reducing the size of laparoscopic instruments. We define as
"needlescopic" those instruments that have a diameter of < or =3 mm. We compared
data from 60 needlescopic cholecystectomies with a matched group of laparoscopic
procedures. No intraoperative complications occurred in either group. Operative
time was 20% longer for the needlescopic operations. Hospital stay was similar
for both groups. Postoperative analgesia requirements for the needlescopic group
were 70% lower than for the laparoscopic group. From a scale (0, no scar visible,
to 10, worst scar), patients scored their scars as 1 for the needlescopic cases
and 5 for the laparoscopic group. Likewise, we have used needlescopic instruments
to perform appendectomy, inguinal herniorrhaphy, adrenalectomy, splenectomy, and
fundoplication. In conclusion, needlescopic procedures are safe and efficient.
While they result in longer operative times, they decrease the need for
postoperative analgesia, which may shorten convalescence and improve the cosmetic
result.
PMID- 9649039
TI - Hand-assisted laparoscopic distal pancreatectomy for pancreatic cystadenoma.
AB - A cystic lesion in the body of the pancreas was detected during staging workup of
a 59-year-old woman with T-cell lymphoma of the tongue. After six cycles of
chemotherapy the pancreatic lesion was unchanged. Suggestive ulceration of the
vulva with edema appeared at the end of chemotherapy. After right vulvar
excision, distal pancreatic resection with splenectomy was carried out by a hand
assisted laparoscopic technique utilizing a small muscle-splitting right lower
quadrant incision. This allowed for palpation of the peritoneal cavity for
evidence of tumor and allowed for safe and expeditious pancreatectomy. The
pancreatic tumor was found to be a serous cystadenoma without evidence of
malignancy. T-cell lymphoma was identified in the spleen and the vulva. The
patient was discharged home on the fifth postoperative day and returned to normal
activity within 2 weeks after operation. Two months after the surgery, computed
tomography demonstrated a 3-cm pseudocyst in the region of the tail of the
pancreas. As the patient was asymptomatic, this required no further therapy.
Minimally invasive surgery together with hand assistance combines the advantages
of both laparotomy and laparoscopy in the surgical management of selected lesions
in the pancreas.
PMID- 9649040
TI - Preliminary results of thoracoscopic Belsey Mark IV antireflux procedure.
AB - Laparoscopic Nissen fundoplication has replaced open approaches for refractory
gastroesophageal reflux disease (GERD) in many major medical centers. Here we
report our preliminary results of the Belsey Mark IV antireflux procedure
performed by video-assisted thoracoscopy (VATS-Belsey). Fifteen patients
underwent VATS-Belsey. The indications for surgery included GERD refractory to
medical therapy (n=10), achalasia (n=2), diffuse esophageal spasms (n=1),
epiphrenic esophageal diverticulum (n=1), and paraesophageal hernia (n=1). The
median operative time was 235 min. There were three conversions to open
minithoracotomy (8-10 cm) necessitated by severe adhesions (n=2) and repair of a
gastric perforation (n=1). The median hospital stay was 4 days. Postoperative
complications included persistent air leaks, requiring discharge with a Heimlich
valve in one patient. There were no perioperative deaths. At a median follow-up
of 19 months, ten patients (66%) were asymptomatic and were not taking any
antacids. One patient who had taken proton pump inhibitors preoperatively
required postoperative H2 blockers for mild heartburn. In three patients,
recurrent GERD symptoms (mean follow-up 6 months) led to laparoscopic takedown of
the Belsey and Nissen fundoplication. One patient with achalasia, who had
recurrent dysphagia after 1 year of relief following VATS myotomy and Belsey,
underwent esophagectomy. The Belsey Mark IV antireflux procedure is technically
feasible by VATS with minimal morbidity. However, our preliminary results suggest
that open thoracotomy for Belsey Mark IV should remain the standard operation for
GERD with poor esophageal motility when a thoracic approach is desired. We have
modified our approach to laparoscopic partial fundoplications (Toupet or Dor) for
severe GERD and poor esophageal motility when an abdominal approach is possible.
PMID- 9649041
TI - Complications in laparoscopic colorectal resection: main types and prevention.
AB - Most colorectal procedures can be done laparoscopically, as has been described by
many authors. In the first 5 years of colorectal laparoscopic surgery, many
complications have ensued, such as intestinal perforation, bleeding, infection,
anastomotic leakage, and dehiscence. In 146 patients who underwent laparoscopic
procedures from December 1991 to August 1996, 92 colorectal resections were
performed. Most resections were performed for malignant diseases (48.9%) and the
most common surgical procedure was rectosigmoidectomy (32.6%). Sixty-six patients
(71.7%) were female, and the mean age was 59.4 years. Transoperative
complications occurred in three patients (3.3%): one sigmoid perforation, one
rectal perforation, and one case of left ureter transection. Postoperative
complications occurred in 24 patients (29.3%): anastomotic leakage (4),
intestinal perforation (1), incisional hernia (4), wound infection (8), shoulder
pain (1), dehiscence of perineal wound (4), and colostomy necrosis (2). We
concluded that laparoscopic colorectal resection is a safe surgical method and
that the rate of complications is similar to that of the conventional method.
PMID- 9649042
TI - Endoscopic transanal rectal stricturoplasty.
AB - This is a report of the techniques used and the outcome in two patients who
underwent endoscopic transanal rectal stricturoplasty. Both patients had rectal
strictures at the site of previous colorectal stapled anastomosis, and had failed
to respond to balloon dilatation. The stricturoplasties were carried out with the
use of a laparoscopic linear cutter passed transanally. In one patient a
colonoscope was used to visualize the stricture, whereas in the second patient a
laparoscope (passed transanally) was used. The operating times were 65 and 59
min, respectively. There were no complications, and both patients were discharged
the next day. Both patients are asymptomatic after 9 and 7 months of follow-up. A
colonoscopy carried out at 6 months has shown patent anastomosis in both
patients. Endoscopic transanal rectal stricturoplasty is a safe and effective
technique in dealing with benign rectal strictures and can be performed in an
outpatient basis.
PMID- 9649043
TI - Retroperitoneal endoscopic lumbar sympathectomy with balloon dissection:
experience with a cadaveric model.
AB - The objective of this study was to determine the feasibility of retroperitoneal
endoscopic lumbar sympathectomy with balloon dissection technique using a
cadaveric model. Retroperitoneal endoscopic lumbar sympathectomy was performed on
10 cadavers. The procedure was combined with balloon dissection to provide easier
visualization and more working space. The outcome was successful in eight
cadavers. Average operating time was 40 min, and visualization was good. The only
major technical problems were perforation of the peritoneum and air leak into the
abdomen. It was concluded that retroperitoneal endoscopic lumbar sympathectomy
with balloon dissection has the advantages of minimal invasiveness, clear
visualization, and controlled blunt dissection. The use of a cadaveric model may
improve the clinical learning curve.
PMID- 9649044
TI - Laparoscopic cholecystectomy for the various types of gallbladder inflammation: a
prospective trial.
AB - Laparoscopic cholecystectomy (LC), the procedure of choice for elective
cholelithiasis, is now also used in the management of acute cholecystitis. In the
various types of gallbladder disease, favorable and unfavorable conditions may
influence the conversion and complication rates. Information about these
conditions may help elucidate the optimal circumstances for LC or indicate when
the procedure is best avoided. We attempted to perform emergency LC on 215
patients with acute cholecystitis. The procedure was successful in 171 patients
(79.5%), and conversion to open cholecystectomy (OC) was needed in 44 (20.5%).
Complications occurred in 37 patients (17%). Uncomplicated acute cholecystitis
was associated with age <50 years, duration of complaint <48 h, temperature <38.5
degrees C, a nonpalpable gallbladder, and an alkaline phosphatase >100 U/L. Acute
gangrenous cholecystitis was associated with a negative gallbladder history,
other associated diseases, temperature >38.5 degrees C, a palpable gallbladder,
and serum bilirubin levels <1 mg/dl. Hydrops was associated with a temperature
<38 degrees C and a leukocyte count of >12,000/cc3, and empyema of the
gallbladder was associated with duration of complaint >48 h and a palpable
gallbladder. The conversion rate of acute gangrenous cholecystitis (40%) was
significantly higher than that of uncomplicated acute cholecystitis (8%) (p <
0.00001, odds ratio=7.7), as well as that of empyema of the gallbladder (12.5%)
(p=0.005, odds ratio=4.7). The conversion from LC to OC in uncomplicated acute
cholecystitis was associated with male sex and with duration of complaint >24 h,
and in gangrenous cholecystitis with age >60 years, a nonpalpable gallbladder,
and a leukocyte count of >15,000/cc3. The complication rates of acute
cholecystitis, hydrops, empyema of the gallbladder, and gangrenous cholecystitis
were 16%, 7%, 22%, and 21%, respectively (p = NS). The total complication rate in
acute cholecystitis tended to be associated with a duration of complaint >48 h
and in gangrenous cholecystitis with male sex, age >60 years, other associated
disease, larger bile stones, and elevated serum bilirubin levels. Generally, LC
is safe in all forms of cholecystitis, with acceptably low conversion and
complication rates, excluding gangrenous cholecystitis. In gangrenous
cholecystitis, a conversion rate of approximately 40% is expected. Predictors of
conversion and complications may be particularly helpful in planning the
laparoscopic approach to acute gangrenous cholecystitis. Patients >60 years of
age, with a nonpalpable gallbladder and with a leukocyte count >15,000/cc3,
frequently need conversion. In men >60 years old, with other associated disease,
with larger bile stones, and with elevated serum bilirubin levels, complications
are frequently expected. Under these conditions, laparoscopic approach should be
undertaken by especially experienced teams, or OC should be considered.
PMID- 9649045
TI - Laparoscopic vs. open cholecystectomy in patients aged 65 and older.
AB - Laparoscopic cholecystectomy (LC) has displaced open cholecystectomy (OC) in the
management of cholelithiasis. However, there are few studies on the role of this
technique in patients who run a high risk of surgical complications. We performed
a prospective study in 264 patients aged >65 years undergoing surgery for
symptomatic cholelithiasis. They were divided into two groups according to the
surgical technique performed: OC (131 patients) and LC (133 patients). Conversion
from LC to OC was necessary in 11 patients (8.3%). Mean surgery time was 70.9 min
for the OC group and 75 min for the LC group. The LC group had a lower rate of
postoperative complications (13.53%) than the OC group (23.6%). The incidence of
mild complications was similar in both groups; however, the rate of moderate
complications was significantly higher in the OC group. Hospital stay was
significantly longer in the OC group (9.9 days) than in the LC group (3.71 days).
These results suggest that LC should be indicated in elderly patients, as they
are better than those obtained with with OC and involve a lower morbidity rate
and shorter hospital stay.
PMID- 9649046
TI - Laparoscopy-assisted endoscopic bowel anastomosis stenosis revision with stapler:
report of two cases.
AB - Anastomosis stenosis is a complication after bowel surgery. We performed
laparoscopy-assisted endoscopic revision of bowel anastomosis stenosis with a
stapler in two cases: first, for secondary anastomosis stenosis 14 months after
sigmoid colon resection, and second, for inadequate-size primary anastomosis
after segmental colon resection requiring immediate revision. A stapler, an
endoscopic linear cutter Endopath ETS (Ethicon Endo-Surgery, Cincinnati, Ohio,
U.S.A.), is transanally inserted and fired once into the stricture to enlarge the
inner lumen. The procedure seems to be fast and safe, less invasive, and cost
effective. This new technique can be used to avoid open surgery in cases of
postoperative anastomosis stenosis as well as initially to increase the
anastomosis diameter of the lower colon.
PMID- 9649047
TI - Omental flap obtained by laparoscopic surgery for reconstruction of the chest
wall.
AB - The reconstruction of complex defects of the chest wall after infection of the
sternotomy wound presents a great challenge. Various options have been described
for these reconstructions using muscle and omental flaps to fill the space and
cover the defect. A case of reconstruction of a large defect of the chest cage
and abdominal wall in a 62-year-old patient is presented. After surgery for
revascularization of the myocardium, the patient developed mediastinitis,
osteomyelitis, and necrosis of the sternum. The pectoralis major muscle was
utilized for the reconstruction, but total loss of the flap occurred. After
debridement, an omental flap obtained by laparoscopy was employed based on the
left gastroepiploic artery. The omentum was transposed without complications
through the abdominal wall defect. An overlay skin graft with the omentum as
receptor bed completed the closure. There are advantages in using minimally
invasive videolaparoscopy compared with laparotomy in obtaining the omentum, with
the same result regarding reconstruction of the defect.
PMID- 9649048
TI - Postoperative ulcer and hemorrhage: an uncommon complication of laparoscopic
Nissen fundoplication.
AB - An unusual postoperative complication of ulceration and hemorrhage during the
postoperative period of a Nissen fundoplication in a patient with severe chronic
periesophagitis is presented. In a review of the literature we could not find a
similar report. The possible etiopathogenic mechanisms are discussed, and
preventive measures are suggested.
PMID- 9649049
TI - Outcome of laparoscopic transabdominal preperitoneal inguinal hernia repair.
AB - The long-term efficacy of laparoscopic inguinal hernia repair is unknown. This
retrospective study was conducted to determine the efficacy of this operation in
comparison with the open technique and to evaluate the possible factors of
recurrence. We have evaluated the clinical outcome in a group of patients who
underwent laparoscopic procedures between January 1995 and December 1996, with
the aim of assessing the incidence of recurrence and of long-term complications.
Sixty-three patients underwent laparoscopic transabdominal preperitoneal repair
by use of a large mesh. We were able to examine 58 of these patients at a median
follow-up time of 15 months since their operation. Four patients had developed a
recurrence, and two patients had significant symptoms consistent with nerve
damage. The recurrence rate of 7% is similar to that reported for open operations
but higher than that reported for early follow-up after laparoscopic operations.
Our study illustrates the value of long-term follow-up for the assessment of
efficacy following laparoscopic inguinal hernia surgery.
PMID- 9649050
TI - Endoscopic surgery of the neck: a new frontier.
AB - Endoscopic dissection and surgical intervention of the neck is a safe and
technically feasible option. A cavity for the operation is made by sharp
dissection after preliminary CO2 insufflation of the fascial planes to induce
surgical emphysema. We successfully performed three endoscopic
parathyroidectomies and five endoscopic hemithyroidectomies without any
complication. The technical details and factors affecting the result of the
operation are described here.
PMID- 9649051
TI - Anterior sacroiliac fusion: a new video-assisted endoscopic technique.
AB - We present a case of sacroiliac fusion performed for an intraarticular
osteochondroma of the sacroiliac joint, which was the cause of severe pain and
disability. Excision of the lesion and sacroiliac fusion were successfully
performed by utilizing minimally invasive surgical techniques. Although the
application of this technique requires a dedicated and highly experienced team,
the encouraging result of our first case, with minimal morbidity and disability
due to the operation, induces us to recommend this technique in sacroiliac
fusion, especially when fusion is combined with additional procedures such as
drainage, biopsy, or excision.
PMID- 9649052
TI - Needlescopic retrograde cholecystectomy.
AB - Needlescopic surgery is a refinement of laparoscopic surgery wherein instruments
smaller than 3 mm are used. The advantage is the minute wounds that heal
imperceptibly. Initial reports of needlescopic cholecystectomy were confined to
uninflamed gallbladders where the antegrade technique was invariably used. This
case demonstrates a needlescopic cholecystectomy by the retrograde approach for
an inflamed gallbladder.
PMID- 9649053
TI - Unretrieved gallstone presenting as an inguinal mass.
AB - We describe a case of a patient 6 months after laparoscopic cholecystectomy who
presented with inguinal pain and a mass. At inguinal exploration, the patient was
found to have an unretrieved gallstone.
PMID- 9649054
TI - Laparoscopic external drainage of a pancreatic pseudocyst associated with
periportal collaterals.
AB - A pseudocyst of the pancreas was detected in a 44-year-old man with alcoholic
chronic pancreatitis. Ultrasound-guided puncture and drainage were attempted but
were unsuccessful because of unexpected bleeding from the collateral veins around
the cyst wall. Consequently, a laparoscopic puncture was performed and proved to
be effective.
PMID- 9649055
TI - A further case of junction of the cystic duct into the left hepatic duct: a real
risk for iatrogenic lesions of the bile ducts.
PMID- 9649056
TI - Uraemic myopathy: fact or fiction.
PMID- 9649057
TI - Plasma exchange in myasthenia gravis.
PMID- 9649058
TI - Metabolic acidosis and nutritional status of patients receiving continuous
ambulatory peritoneal dialysis (CAPD)
PMID- 9649059
TI - Use of single dose low-molecular-weight heparin in long hemodialysis.
AB - Low-molecular-weight (LMW) heparin has recently been used for anti-coagulation in
maintenance hemodialysis. The LMW heparin was administered as a single bolus in
hemodialysis that usually lasted for four hours or less. The regimen for
administering LMW heparin in hemodialysis of longer duration (5 hours or more) is
not well documented and manufacturers recommend a supplementary dose equivalent
to one-quarter of the initial dose to be given at 4 hours after the commencement
of hemodialysis. In this study, we explored whether administering a single dose
of LMW heparin is feasible in hemodialysis of longer duration. Maintenance five
hour hemodialysis sessions were performed in nine uremic patients with two
different heparin regimens: single dose of LMW heparin (nadroparin) 12,500 ICU
AXa at the beginning of dialysis or a priming dose of nadroparin 10,000 ICU AXa
at the beginning of dialysis followed by a supplementary dose of nadroparin 2,500
ICU AXa at the beginning of the fifth hour of dialysis. Clots in the airtraps or
clotting of the dialyser were not observed in hemodialysis with the single dose
heparin regimen. The anti-Xa activities at different time intervals during
dialysis were above the therapeutic range of 0.5 U/ml except towards the end of
the hemodialysis treatment. There was no difference between anti-Xa activities
determined in dialysis sessions using two different regimens of LMW heparin at
any individual time interval. The anti-thrombotic effect determined by the area
under the time response curve for anti-Xa activity was comparable in the two LMW
heparin regimens. Hence, our findings suggest a single bolus dose of LMW heparin
(nadroparin) at 12,500 ICU AXa provides adequate, safe, and effective anti
coagulation for five-hour hemodialysis. This practice is convenient and avoids
the necessity of administering a double dose of LMW heparin.
PMID- 9649060
TI - Exhaustion of vascular endowment in hemodialysis: proposal for a permanent inlet
access.
AB - The subcutaneous reservoir is a new vascular access for patients on regular
hemodialysis (HD). A double chamber in Titanium- Pirolytic Carbon with siliconic
boreable superior caps is inserted in to a subcutaneous subclavian side, and
always in subcutis connected to two siliconic catheters located in the right
jugular resulting in the right atrium. The puncture of each chamber is performed
with a special hemodialysis-cannula telescopically assembled on a "dilatation
tube", in which a stylet is inserted. In correct sequence, the cutaneous planes
and the caps are bored, dilated, and finally the HD cannula after sliding over
the previous structures is positioned in the inner chamber, closing the HD
circuit. In our study two patients were implanted, with a survival of 24 months,
good compliance, no cardiovascular impairments and lack of catheteral pathology.
PMID- 9649061
TI - Myoglobin clearance during continuous veno-venous hemofiltration with or without
dialysis.
AB - The management of acute myoglobinuric renal failure, the major complication of
rhabdomyolysis, continues to be a treatment dilemma for the clinician as limited
therapeutic options are available. Previously, we have demonstrated that
continuous arteriovenous hemofiltration (CAVH) is an effective technique for
removing myoglobin in an animal model. In the present study, swine were
administered four grams of equine myoglobin intravenously and underwent the
continuous veno-venous hemofiltration (CVVH) procedure for six hours each.
Animals were studied in each of the following groups: CVVH at a pump rate 100
ml/minute, CVVH at a pump rate 200 ml/minute and CVVH at a pump rate 100
ml/minute plus dialysis at a dialysate flow rate of one Liter/h. Once the
filtering process was initiated there was a rapid and sustained production of
ultrafiltrate in all groups. The amount of myoglobin excreted in the
ultrafiltrate over the six-hour filtering period was 688, 948 and 570 mg which
corresponded to 17, 24 and 14 percent of the administered dose, respectively, for
the three treatments. In comparison to previous CAVH experiments, CVVH removed
more circulating myoglobin and the addition of the dialysis component did not
appear to improve removal. Based on these findings, it appears that the CVVH
hemofiltration system is a viable option for the removal of systemic myoglobin.
PMID- 9649062
TI - Reduction of mononuclear cytokine production in hemodialysis patients treated
with steam-sterilized low-flux polysulphone membranes.
AB - An increased cytokine production, correlated with long term complications of
uremic disease, has been described during hemodialysis. To identify possible
differences in the cytokine release of differently sterilized membranes, we
enrolled six uremic patients on chronic hemodialysis. The patients underwent
dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG)
for at least three months (A1), they were then switched to steam-sterilized
polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one
(B1) and two months (B2) were carried out. A final evaluation (A2) was made one
month after switching back to F6 dialyzers. At each time period, samples were
drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover,
dialysate samples were collected to test endotoxin levels. C3a and C5a levels
were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE
levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality
dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1;
falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2:
284, p<0.01. Post-dialysis levels followed the same pattern. No correlation
between the dialysate endotoxin level and cytokine release was found. Complement
activation did not change and in all the phases of the study no anti-ETO IgE was
detected in any of the subjects. Our data suggest that the steam sterilized
polysulphone membrane induces a lower cytokine release than the ETO sterilized
membrane, although the mechanism by which it does so remains to be clarified.
PMID- 9649063
TI - A new method of mechanical circulatory support with an implantable multichamber
pump system (IMPS): presentation and first experimental results.
AB - This paper presents a new cardiac support device for left ventricular failure
which consists of two inflatable bellows positioned dorsally and ventrally to the
left ventricle. The implantable multichamber pump system (IMPS) is driven by a
pneumatic pump system and controlled by a microcomputer using ECG-trigger and
pacemaker modules. It was implanted via thoracotomy in 8 pigs. The circulatory
parameters were measured in the animals on beta-blockers, with cardiac failure
and in ventricular fibrillation with an activated (IMPS on) and deactivated (IMPS
off) system. IMPS significantly increased the left ventricular pressure (LVPsys
IMPS off: 63 +/- 6 mmHg vs IMPS on: 96 +/- 8 mmHg) and the blood pressure in the
common carotid artery (BPca, IMPS off: 69/38 mmHg vs IMPS on: 95/40 mmHg). The
IMPS proved to be highly efficient in the therapy of animals with acute cardiac
failure and in ventricular fibrillation in the experimental model. Apart from its
efficiency the advantages with this system are the ease of handling and its high
biocompatibility due to the lack of contact with circulating blood.
PMID- 9649064
TI - Development of vibrating flow pump for left ventricular assist circulation.
AB - Vibrating flow pump (VFP) can generate high frequency oscillated blood flow
within 10-40 Hz. In this study, new type VFP was developed as a ventricular
assist device. Left Ventricular assist circulation using VFP were performed as
aseptic animal experiments using goats. hemodynamic parameters were recorded
continuously at awake state. Driving frequency of VFP was 25 Hz and pump flow
rate was controlled to approximately 2 l/min. Frequency of VFP was 25 hz and pump
flow rate was controlled to approximately 2 L/min. Frequency analysis method was
used for analyzing hemodynamics. The peak of power was observed at 25 Hz from the
Fourier transformation of blood flow waveform. Systemic vascular resistance was
decreased by the start of left ventricular assistance using oscillated blood
flow. No fatal arrhythmia was observed during this study. As the conclusion, new
type VFP has a sufficient performance for left ventricular assistance. Small size
blood pump may be enabled by the oscillated blood flow because VFP is driven at
high frequency moving with short stroke volume.
PMID- 9649065
TI - High density culture of immortalized liver endothelial cells in the radial-flow
bioreactor in the development of an artificial liver.
AB - Liver endothelial cells are important components of the tissue along the hepatic
sinusoid. They are responsible for microcirculation in the liver and scavenger
functions. It would therefore be important to include these cells in any hybrid
type of artificial liver in addition to hepatocytes. However, it is difficult to
culture these cells in vitro. The development of a liver endothelial cell line,
which maintains the characteristics of the primary culture, would thus be of
great benefit in the development of an artificial liver. In the present study we
established immortalized liver endothelial cells from the liver of an H-2Kb-tsA58
transgenic mouse, which harbors the SV40 TAg gene. Hepatic sinusoidal cells
isolated from H-2Kb-tsA58 mouse proliferated in the presence of gamma-interferon
at 33 degrees C. Four clones were established, out of which clone M1 had the
highest amounts of PGI2 production, as well as plasminogen activator activity and
internalized acetylated low density lipoprotein. On culture dishes the M1 cells
grew individually and spread. Sieve plates on the cell surface were not readily
visible, but small pores were detected under electron microscopic observation.
These results suggest that M1 clone cells originated from liver endothelial
cells. Moreover it was possible to culture the immortalized liver endothelial
cells in a radial-flow bioreactor for 5 days, with a maximum 6-keto prostaglandin
F1alpha production of 25 microg per day. This suggests that immortalized liver
endothelial cells and a radial-flow bioreactor can prove useful tools in the
development an artificial liver.
PMID- 9649066
TI - Salvage and reinfusion of chyle in closed chest injury.
AB - The aim of this study was to describe a system of salvaging and reinfusing chyle
which accumulated in the right pleural cavity of a patient after a thoracic duct
lesion caused by a closed chest injury associated with amyelic fracture of the
dorsal spine D10-D11. The chyle was collected in a reservoir (BT 844 Dideco),
transferred by an electronic pump (BT 797 recovery Dideco) to a storage bag,
microfiltered and then reinfused to the patient A solution was needed to prevent
the patient with severe chylothorax, from having immunological and metabolic
imbalance. The long period of conservative treatment with our system was imposed
by the onset of acute post-traumatic myocardic infarction which delayed surgery.
From experience gained, we can say that using total parenteral nutrition, chyle
can not only be salvaged but also reinfused, respecting the strict rules of
hygiene.
PMID- 9649067
TI - Mechanical and dynamic aspects of voice production as related to voice therapy
and phonosurgery.
AB - Laryngeal framework surgery can change the position and tension of the vocal
folds safely without direct surgical intervention in the vocal fold proper. Some
23 years of experience with phonosurgery have proved its usefulness in treating
dysphonia related to unilateral vocal fold paralysis, vocal fold atrophy, and
pitch-related dysphonias . Meanwhile, much information about the mechanism of
voice production has been obtained through intraoperative findings of voice and
fiberscopic examination of the larynx . Based on such knowledge together with
information obtained through model experiments, the human vocal organ was
reconsidered mainly from the mechanical view point, and the roles of voice
therapy and singing pedagogy were discussed in relation to phonosurgery. The
vocal organ may not be an ideal musical organ and is rather vulnerable, but its
potential is enormous.
PMID- 9649068
TI - Suitability of minidisc (MD) recordings for voice perturbation analysis.
AB - A new digital recording format, Minidisc (MD), shows promise for high-quality
voice recordings. It is available in a portable size and uses magneto-optical
recording techniques on a miniature compact disc. The disc can be recorded an
unlimited number of times with essentially the same playback life span: however,
the digital recording technique uses a data compression algorithm that may
interfere with acoustic voice perturbation analysis. This study investigated what
effects this compression may have and whether the MD format is viable for use in
this application. The MD format was evaluated by traditional synthetic test
signals used on recording devices. In addition, human phonation recorded on
Digital Audio Tape (DAT) was used as the input to the MD. The output of the MD
was then compared to the original DAT recording. The two signals were analyzed
for long- and short-term perturbation measures, and their waveforms were visually
inspected. The results indicated that the MD format performed as well as the DAT
format in all areas of standard tests, with the exception of signal-to-noise
(S/N) ratio. S/N ratio for the MD was approximately 10 dB less than for the DAT
under normal operating conditions; however, in comparing perturbation measures on
normal human vowels, there were no significant differences between the two
formats, i.e., no distortions in voice perturbation were introduced by the MD
record/playback process.
PMID- 9649069
TI - A hardware-software system for analysis of video images.
AB - The purpose of this paper is to describe a software/hardware system for the
analysis of digitized video images and a number of applications for which it may
be used. The system described includes a Macintosh computer, a frame-grabber
board, and Image, a public domain software program available at no cost from the
U.S. National Institutes of Health. In our clinic and laboratory, this system is
routinely used to make quantitative measurements from videofluoroscopic x-ray
images of dynamic swallow studies and studies performed to assess velopharyngeal
dysfunction in speech. It can also be used to examine various laryngeal
parameters obtained from videotaped endoscopic and stroboscopic examinations.
With a videocamera attached to a microscope, the system permits quantitative
analysis of tissue characteristics, e.g., thickness of epithelial or connective
tissue layers of the vocal folds. The relatively low cost and ease of use of the
image analysis system make it a particularly attractive option when quantitative
assessment of clinical or research materials in video format is desirable.
PMID- 9649070
TI - Optimal glottal configuration for ease of phonation.
AB - Recent experimental studies have shown the existence of optimal values of the
glottal width and convergence angle, at which the phonation threshold pressure is
minimum. These results indicate the existence of an optimal glottal configuration
for ease of phonation, not predicted by the previous theory. In this paper, the
origin of the optimal configuration is investigated using a low dimensional
mathematical model of the vocal fold. Two phenomena of glottal aerodynamics are
examined: pressure losses due to air viscosity, and air flow separation from a
divergent glottis. The optimal glottal configuration seems to be a consequence of
the combined effect of both factors. The results agree with the experimental
data, showing that the phonation threshold pressure is minimum when the vocal
folds are slightly separated in a near rectangular glottis.
PMID- 9649071
TI - Effects of lung volume on vertical larynx position during phonation.
AB - The vertical position of the larynx seems to be relevant to voice function. As a
high vertical larynx position is often seen in hyperfunctional and strained
voices, a lowering of a habitually elevated larynx is sometimes a specific goal
in clinical voice therapy and different larynx-lowering exercises are used to
achieve this goal. Earlier investigations have shown that pitch and to some
extent also vocal loudness are relevant to vertical larynx position. In the
present investigation, we examine if lung volume affects vertical larynx
position. Using a multi-channel electroglottograph, the larynx position was
measured in 29 healthy, vocally untrained subjects, who phonated at different
lung volumes, pitches, and degrees of vocal loudness. The main results were that
high lung volume was clearly associated with a lower larynx position as compared
to low lung volume. In addition, vertical larynx position was strongly correlated
with pitch. Both of these dependencies were shown to be stronger in males than in
females. Our results suggest that lung volume is a factor that is highly relevant
to larynx height in untrained subjects.
PMID- 9649072
TI - Data on subglottal pressure and SPL at varied vocal loudness and pitch in 8- to
11-year-old children.
AB - Phonation threshold pressure has been defined as the minimum subglottal pressure
to generate phonation. Previous research has indicated that children may
habitually employ higher subglottal pressures than adults. In the present
investigation sound pressure level (SPL) and subglottal pressures at different
pitch levels were measured at and above phonation threshold in nine children.
Phonation threshold values were scattered in reasonable agreement with Titzes'
prediction, although a discrepancy was noted regarding the frequency dependence
in some voices. At normal conversational loudness and loudest level of phonation
the children's Ps values were between two to four and four to eight times the
predicted threshold values, respectively. At normal conversational loudness and
habitual pitch subglottal pressures were lower than those previously observed for
children, but similar to those found for female adults. The SPL in softest and
loudest phonation were somewhat lower as compared to previous phonetogram data
for children and for female adults. At normal loudness and habitual pitch the SPL
values were similar to those of female adults. For a doubling of Ps mean SPL
increased by 10.5 dB on the average.
PMID- 9649073
TI - The effects of time constraints on phonatory stability in normally speaking adult
women.
AB - Forty normally speaking women sustained /a/ five times in two conditions, untimed
and timed. In the untimed condition, phonation began whenever the subject felt
ready. The timed task required subjects to begin phonation as quickly as possible
after the examiner's signal. Conditions were counterbalanced across subjects.
Jitter and shimmer values were obtained on a Kay Elemetrics Computerized Speech
Lab (Pine Brook, NJ). Three distinct patterns of change emerged for jitter and
shimmer from the untimed to the timed condition, reflecting either decreases,
increases, or no change in values. These changes in jitter and shimmer values
across conditions are related to a reaction time model of "bias toward accuracy."
PMID- 9649074
TI - Relating objective measurements to expert evaluation of voice quality in Western
classical singing: critical perceptual parameters.
AB - Communication between voice pedagogues and voice scientists is often impeded by
reliance on colorful and sometimes seemingly contradictory descriptions of vocal
production and voice quality. A recent study identified perceptual criteria which
are generally used by voice experts for the assessment of voice quality in
classical singing. In the present study, performances by singers of various voice
types and levels of accomplishment were rated by panels of expert voice teachers
according to four perceptual criteria: "resonance/ring," "color/warmth,"
"clarity/focus," and "appropriate vibrato." Subjective ratings were related to
objective measurements taken from acoustic analysis of the voice signal. Possible
acoustic correlates of critical perceptual parameters influencing judgments of
voice quality were thus identified. Results could help bridge the terminology gap
between vocal artists and scientists, and help to promote understanding of the
way in which acoustic stimuli influence perception of voice quality.
PMID- 9649075
TI - Voice problems and risk factors among aerobics instructors.
AB - Fifty female and four male aerobics instructors completed a questionnaire
pertaining to vocal problems and variables that could indicate an increased risk
for developing problems. The questions concerned teaching experience, physical
data regarding instructional facilities, method of voice projection, music
volume, history of illness, allergies, voice loss, hoarseness, smoking habits,
and knowledge of vocal hygiene. The results showed that a significant number of
instructors experienced partial or complete voice loss (44%) during and after
instructing, as well as increased episodes of voice loss, hoarseness, and sore
throat unrelated to illness since they began instructing. Significant variables
associated with voice problems included sore throat and hoarseness following
instruction, and shouting to cue the participants. It was also found that very
few instructors in this study had any knowledge of vocal hygiene techniques.
PMID- 9649076
TI - Have women's voices lowered across time? A cross sectional study of Australian
women's voices.
AB - Various aspects of our communication are well known to have changed over time (1
3). This article describes a cross-sectional study that examined the acoustic
characteristics of two groups of Australian women aged 18-25 years from
recordings made in 1945 and 1993 and investigated the possible changes in the
voice across generations. Archival recordings from 1945 which had been used in a
longitudinal study (4) were compared to recordings made in 1993. The results of
this study show that women in 1993 have significantly deeper voices than women of
the same age recorded in 1945. The possible factors influencing this change are
discussed.
PMID- 9649077
TI - Variations in adductor spasmodic dysphonia: acoustic evidence.
AB - Acoustic analysis was used to gain information about the normal, as well as the
abnormal acoustic events associated with adductor spasmodic dysphonia (ADSD).
This analysis was completed to determine whether specific acoustic events could
be used to differentiate the voice of individuals with ADSD from those with
normal voice. A group comparison between 14 women diagnosed with ADSD and 14
women (age-matched) with no evidence of vocal pathology or vocal dysfunction was
completed. Phonatory breaks, aperiodicity, and frequency shifts, acoustic
parameters previously identified in ADSD, were found throughout sustained vowel
productions. The duration of the phonatory breaks and aperiodic segments was
calculated and the amount of frequency shift was determined. The location of each
acoustic event was marked relative to the onset of the vowel production. The
subjects with ADSD presented with normal phonation and various amounts of each of
the three acoustic parameters. Aperiodic segments primarily characterized the
phonation of ADSD, followed by frequency shifts and phonatory breaks. The
location of each of these acoustic events was within the midportion of the vowel
production. The advantages of segmenting the acoustic waveform into these
measures and separating the spasmodic events from normal phonation when examining
laryngeal motor control of spasmodic dysphonics is discussed.
PMID- 9649078
TI - Spasmodic dysphonia and vocal fold paralysis: outcomes of voice problems on work
related functioning.
AB - Patients at a university voice disorder clinic diagnosed with spasmodic dysphonia
(SD, n = 68) or vocal fold paralysis (VFP, n = 57) reported vocal symptoms and
adverse work outcomes in contrast to a nondisordered group (ND, n = 68). Patients
with SD most frequently cited symptoms of effortfulness (57%) and weakness (54%),
VFP cited hoarseness (70%) and weakness (60%), while the nondisordered reported
hoarseness (28%). SD and VFP produced greater (p< .05) adverse work outcomes than
the nondisordered in the past (SD: 65%, VFP: 41%, ND: 3%), potential future (SD:
78%, VFP: 65%, ND: 19%), and current job performance (SD: 64%, VFP: 46%, ND: 2%).
These disorders significantly disrupt socioeconomic outcomes and research is
needed to improve functional ability and quality of life.
PMID- 9649079
TI - Transoral laryngeal surgery under flexible laryngovideostroboscopy.
AB - Although direct microlaryngoscopic surgery is universally accepted as the
standard procedure for endolaryngeal surgery, general anesthesia and direct
laryngoscopy are necessary during the procedure. Suspended laryngeal position
also impedes intraoperative functional monitoring. Transoral laryngeal surgery
under indirect laryngeal mirror or telescope has the advantage of sparing general
anesthesia and direct laryngoscopy, but lower precision, difficult manipulation,
and a high patient cooperation requirement make the procedure of limited
application. Trying to overcome the above shortcomings, transoral laryngeal
surgery under flexible laryngovideostroboscopy (FLVS) is undertaken at our
institute. The surgery is performed at an outpatient office under topical
anesthesia, with the help of high-resolution fiberoptic stroboscopy, high-quality
CCD videocamera, and monitor. From October, 1993 to March, 1996, 157 patients
with selected laryngeal problems were operated upon using this technique, and 150
patients smoothly completed the procedure with satisfactory results. The
technique is highly effective, especially for limited-manipulation, lower
precision procedures and for patients who are not candidates for general
anesthesia. With proper patient selection, this is a cost-effective surgery of
low invasiveness and high applicability.
PMID- 9649080
TI - Acoustical analysis and perceptual evaluation of tracheoesophageal prosthetic
voice.
AB - Voice analysis was performed on 21 "standard" laryngectomized, male patients with
a Provox voice prosthesis, along with an age- and sex-matched control group of 20
normal speakers, using acoustical analyses (MDVP and CSL, Kay Elemetrics Corp.),
maximum phonation time measurements, and perceptual evaluations. Comparison
between MDVP and CSL revealed that the latter was not useful for the analysis of
laryngectomized prosthetic voices. In contrast, MDVP seems suitable for this
purpose, and contains a large number of parameters that significantly
differentiate between patient and control speakers, as did the perceptual ratings
and the maximum phonation time. Fundamental frequency appeared to be comparable
for patients and control speakers. A significant influence of stoma occlusion and
age was found for some voice parameters. Factor analyses showed correlations
between the different MDVP parameters and correlations between the MDVP
parameters and the perceptual ratings.
PMID- 9649081
TI - Microphone and electroglottographic data from dysphonic patients: type 1, 2 and 3
signals.
AB - Recently, it has been suggested that statistics which are dependent upon the
reliable extraction of a single fundamental period, such as jitter and shimmer,
are valid only for nearly periodic signals. This study explored the incidence of
nearly periodic and nonperiodic microphone and electroglottographic signals
obtained from 202 dysphonic patients. It was found that approximately 42% were
type 1 (nearly periodic); approximately 35% were type 2 (containing bifurcations,
modulations or subharmonic structure); and approximately 22% were type 3
(chaotic). Discriminating between type 2 and 3 signals was very difficult for 40%
of the signals which were ultimately rated type 3. This was due to the brevity of
the apparently chaotic segment, and/or the persistence of some harmonic structure
within the chaos. Irrespective of that difficulty, the results suggest that there
may be a substantial incidence of nontype 1 signals in a given clinical
population. It was concluded, therefore, that signal typing is a necessary step
in the analyses of microphone and electoglottographic data.
PMID- 9649082
TI - Assessing the role of case mix in cesarean delivery rates.
AB - OBJECTIVE: Implicit in comparisons of unadjusted cesarean rates for hospitals and
providers is the assumption that differences result from management practices
rather than differences in case mix. This study proposes a method for comparison
of cesarean rates that takes the effect of case mix into account. METHODS: All
women delivered of infants at our institution from December 1, 1994, through July
31, 1995, were classified according to whether they received care from community
based practitioners (N=3913) or from the hospital-based practice that serves a
higher-risk population (N=1556). Women were categorized according to both
obstetric history (nulliparas, multiparas without a previous cesarean, multiparas
with a previous cesarean) and the presence of obstetric conditions influencing
the risk of cesarean delivery (multiple birth, breech presentation or transverse
lie, preterm, no trial of labor for a medical indication). We determined the
percent of women in each parity-obstetric condition subgroup and calculated a
standardized cesarean rate for the hospital-based practice using the case mix of
the community-based practitioners as the standard. RESULTS: The crude cesarean
rate was higher for the hospital-based practice (24.4%) than for the community
based practitioners (21.5%), a rate difference of 2.9% (95% confidence
interval=0.4%, 5.4%; P=.02). However, the proportion of women falling into
categories conferring a high risk of cesarean delivery (multiple pregnancy,
breech presentation or transverse lie, preterm, no trial of labor permitted) was
twice as high for the hospital-based practice (24.4% hospital, 12.1% community).
The standardization indicates that if the hospital-based practitioners had the
same case mix as community-based practitioners, their overall cesarean rate would
be 20.1%, similar to the 21.5% rate of community providers (rate difference=
1.4%, 95% confidence interval =-3.1%, 0.3%; P=.11). CONCLUSION: Standardization
for case mix provides a mechanism for distinguishing differences in cesarean
rates resulting from case mix from those relating to differences in practice. The
methodology is not complex and could be applied to facilitate fairer comparisons
of rates among providers and across institutions.
PMID- 9649083
TI - Effect of maternal carbohydrate metabolism on fetal growth.
AB - OBJECTIVE: To determine the effect of maternal carbohydrate metabolism and
anthropometric characteristics on fetal growth. METHODS: Eight pregnant women in
the third trimester with unexplained fetal growth restriction (FGR) and 11 women
with normal pregnancies in the third trimester were evaluated for maternal
carbohydrate metabolism, using oral glucose tolerance tests and hyperinsulinemic
euglycemic clamps. These data and maternal anthropometric characteristics
subsequently were related to relative birth weight, defined as observed birth
weight x 100/50th percentile birth weight. RESULTS: The women with FGR
pregnancies were more insulin sensitive than were controls (21.6+/-4.4 versus
16.7+/-4.8 micromol/kg x min, P < .05) and showed reduced insulin and glucose
areas under the curve (96,293+/-25,870 versus 145,291+/-49,356 pmol/L, P < .03;
1057.0+/-184.7 versus 1210.1 +/-85.9 mmol/L, P < .05, respectively). No
differences were seen in fasting plasma glucose, insulin and human placental
lactogen samples, age, height, pregravid weight, weight gain, and parity. In all
patients, maternal insulin sensitivity and weight gain correlated well with
relative birth weight (r =-.65, P < .002; r=.68, P < .001, respectively). When
the same analysis was computed separately in the groups, insulin sensitivity
exhibited a strong negative correlation with relative birth weight in the FGR
group but not in controls (r=-.84, P < .007; r=-.54, P=.08, respectively).
Conversely, in control women the best correlation between relative birth weight
and the other variables studied was seen with maternal weight gain (r=.82, P <
.002). CONCLUSION: Women with unexplained FGR have a different glucose metabolic
pattern than do normals. We speculate that increased insulin sensitivity leads to
a reduction in metabolic substrates for fetal growth.
PMID- 9649084
TI - Polycystic ovaries in women with gestational diabetes.
AB - OBJECTIVE: To examine the occurrence of polycystic ovaries (PCO) in women with
gestational diabetes mellitus (GDM). METHODS: This was a retrospective
comparative study of ultrasonographic findings of ovaries in 31 women with GDM
and 30 healthy controls matched according to maternal age and body mass index
(BMI). Women who presented evidence of impaired glucose tolerance during
pregnancy were excluded from the control group. Transvaginal ultrasonographic
examination was performed during the follicular phase of the menstrual cycle,
after breast-feeding had been discontinued. RESULTS: Polycystic ovary was a more
frequent finding among women with GDM than among controls: 14 women with GDM
(44%) and two controls exhibited PCO. No differences were found in BMI before
pregnancy or in the weight gain during pregnancy between the groups. No
difference was observed in the mean birth weight of the infants between the study
groups. CONCLUSION: Polycystic ovaries were a common finding among women with
GDM. The data suggest that women with PCO are at risk for developing GDM and
should be screened accordingly.
PMID- 9649085
TI - Elevated maternal serum relaxin concentrations throughout pregnancy in singleton
gestations after superovulation.
AB - OBJECTIVE: To test the hypothesis that superovulation results in elevated
maternal circulating relaxin concentrations throughout the second and third
trimesters of pregnancy, independent of the pattern of hCG secretion. METHODS:
Two groups of women with singleton gestations were studied: a group of nine women
who achieved pregnancy after stimulation with human menopausal gonadotropin and a
group of six women who achieved pregnancy without prior stimulation. Peripheral
blood samples were drawn approximately every 5 weeks throughout the second and
third trimesters. Serum relaxin concentrations were measured using a human
relaxin-specific enzyme-linked immunosorbent assay; hCG was measured by an
immunofluorometric assay. RESULTS: The stimulated group had significantly higher
relaxin levels throughout pregnancy (P=.007, multivariate analysis of variance)
than did nonstimulated controls. The mean relaxin level in stimulated patients
was 1.78 ng/mL (95% confidence interval [CI] 1.5, 2.17) and in nonstimulated
subjects the level was 0.73 ng/mL (95% CI 0.59, 1.25). Spline fits demonstrated
that stimulated patients had higher relaxin levels throughout the second and
third trimesters. There was no significant difference in hCG concentrations
between the two groups (P=.61). CONCLUSION: In singleton gestations after
superovulation, maternal serum relaxin concentrations are significantly higher
throughout the second and third trimesters of pregnancy. These differences are
independent of the pattern of hCG secretion. It appears that luteal relaxin
secretion is controlled by factors in addition to hCG.
PMID- 9649086
TI - Neonatal group B streptococcal infection in a managed care population. Perinatal
Group B Streptococcal Infection Study Group.
AB - OBJECTIVE: In a health maintenance organization population, we determined the
incidence of early-onset (at less than or equal to 7 days) neonatal group B
streptococcal (GBS) disease, the sensitivity and prevalence of labor risk
factors, the adherence to a protocol for intrapartum antibiotics, and the costs
for care of and outcomes of affected infants. METHODS: Mothers and infants at
four health maintenance organization hospitals in northern California in 1989 to
1995 were studied retrospectively using computerized databases and chart review.
In 1994, two of the four hospitals had adopted protocols similar to the ACOG
recommendations for intrapartum antibiotics for women with labor risk factors
(preterm, temperature 100.4F or higher, or rupture of membranes (ROM) 18 hours or
more). RESULTS: Among the 79,940 live births, the incidence of early-onset
neonatal GBS infection was higher among preterm than among term infants (3.1
compared with 0.9 per 1000). Before protocol adoption, 68% of 65 infants with GBS
had mothers with labor risk factors. Approximately 18% of all mothers had labor
risk factors: 7.7% had preterm delivery, and 10.6% had term delivery with fever
and/or ROM 18 hours or more. At the two hospitals that adopted GBS protocols, GBS
incidence was reduced from 1.3 per 1000 in the preprotocol period to 0.8 per 1000
in the postprotocol period (P=.08). Six cases of neonatal GBS occurred after
protocol adoption. Of these, four were not preventable under the protocol and two
might have been preventable if protocol had been followed. Three of the 19
preterm infants with group B streptococcal disease died. CONCLUSION: Risk factor
based protocols hold some promise to reduce GBS disease, but clinical strategies
to promote protocol adherence are needed.
PMID- 9649087
TI - Oral quinolone in the treatment of experimental polymicrobial puerperal infection
in rabbits.
AB - OBJECTIVE: To evaluate the efficacy of oral levofloxacin in the treatment of
experimental polymicrobial puerperal infection in the rabbit. METHODS: Timed
pregnant rabbits were anesthetized on day 29 or 30 of a 31-day gestation and 106
colony-forming units each of Escherichia coli, group B streptococcus, and
Staphylococcus saccharolyticus were inoculated endoscopically in the cervices.
Labor was induced with intramuscular oxytocin 16 hours later if it had not
occurred spontaneously. The animals then were observed every 3 hours for fever;
when a temperature of 104F was reached, treatment was begun. Animals were
assigned randomly in a blinded, placebo-controlled manner to received oral
levofloxacin (10 mg/kg/day) or placebo and were treated twice daily for 4-5 days.
The animals were killed and necropsy was performed 4-6 hours after the last dose.
Specimens for culture were taken from uterine horns, peritoneum, and blood.
Levofloxacin concentrations were determined from blood samples at necropsy.
Clinical cure of fever, eradication of microbes, and presence of uterine
abscesses at necropsy were assessed. RESULTS: Compared with placebo-treated
rabbits, levofloxacin-treated animals had a significantly greater number of
clinical cures (nine of 11 versus four of 12, P=.027) and significantly more
eradication of E coli (ten of 11 versus five of 12, P=.022). Four uterine
abscesses were seen in 12 placebo-tested animals, compared with none of 11
levofloxacin-tested animals (P=.093). There was no difference in eradication of
group B streptococcus between the two groups. No blood cultures were positive for
organisms in any animal. Levofloxacin was detected in all treated animals, but at
low levels (less than 1 microg/mL). CONCLUSION: Treatment of experimental
puerperal infection with oral levofloxacin in rabbits resulted in significantly
more clinical cures and eradication of E coli compared with treatment with
placebo.
PMID- 9649088
TI - Longitudinal assessment of endocervical canal length between 15 and 24 weeks'
gestation in women at risk for pregnancy loss or preterm birth.
AB - OBJECTIVE: To determine the weekly cervical shortening rates of the endocervical
canal between 15 and 24 weeks' gestation in women at risk for pregnancy loss or
spontaneous preterm birth. METHODS: We performed a retrospective cohort study of
transvaginal sonographic measurements of the endocervical canal length done at
least twice between 15 and 24 weeks' gestation in women at risk for pregnancy
loss and spontaneous preterm birth. The ultrasound diagnosis of cervical
incompetence was defined as progressive shortening of the endocervical canal
length to 2 cm or less either spontaneously or after application of transfundal
pressure. Multivariable linear regression models were developed to determine the
weekly crude rate of endocervical canal length shortening rates in cases of
competent cervices and incompetent cervices, with incompetent cervices further
stratified as those diagnosed at 15-19 weeks' and 20-24 weeks' gestation.
Comparisons of the models for weekly rate of endocervical canal length shortening
were performed. RESULTS: The endocervical canal lengths were measured in 61 women
(180 measurements) who did not develop ultrasound evidence of cervical
incompetence and 28 women (103 measurements) who had ultrasound evidence of
cervical incompetence. Between 15 and 24 weeks' gestation, competent cervices had
a nonsignificant rate of endocervical canal length shortening (-0.03 cm/week).
During this period in gestation, incompetent cervices had significantly greater
endocervical canal length shortening (-0.41 cm/week, P < .001). The rate of
endocervical canal length shortening of incompetent cervices diagnosed between 15
and 19 weeks' gestation was -0.52 cm/week (P < .001). The rate of endocervical
canal length shortening in incompetent cervices diagnosed between 20 and 24
weeks' gestation was significant and varied from -0.49 cm/week to -0.80 cm/week
at 20 and 24 weeks' gestation, respectively (P < .001). The models describing the
rate of cervical shortening in the two groups of incompetent cervices were
significantly different (P < .001). The sonographic detection of endocervical
canal length shortening in the 28 cases of cervical incompetence was identified
at a median (range) gestational age of 20 (16-24) weeks. CONCLUSION: Weekly rates
of endocervical canal length shortening were established, which may be useful for
detecting and managing cervical incompetence in high-risk women examined with
cervical sonography.
PMID- 9649089
TI - Preterm contractions in community settings: I. Treatment of preterm contractions.
AB - OBJECTIVE: To explore how physicians in community hospitals (non-level III
nursery facilities) diagnose preterm labor and treat women with preterm
contractions. METHODS: Chart audits were performed for women presenting with
preterm contractions at a network of 11 Wisconsin non-level III hospitals.
RESULTS: Ninety percent (239 of 266) of the women presenting with premature
contractions agreed to participate. The average gestational age was 31.6 weeks'
gestation. Only 44 (17%) of these women had any cervical change with their
contractions. However, tocolytic agents were used frequently, regardless of
whether cervical changed occurred (61%) or not (76%, P=.10), and tocolytics were
prescribed frequently upon discharge for those patients who left the hospital
(54% of those with cervical change versus 62% in those without changes, P=.57).
Examining the use of appropriate treatments for women who did deliver
prematurely, we found that only 26% of women who delivered prematurely received
antenatal antibiotics to prevent group B streptococcal disease in the newborn,
and only 33% of those who delivered at 34 weeks' gestation or earlier received
corticosteroids to accelerate fetal lung maturity. CONCLUSION: Women presenting
at community hospitals with preterm contractions but no evidence of labor are
overtreated frequently with agents of equivocal benefit, whereas those who have
active labors and deliver are not receiving agents such as steroids or
antibiotics that have been shown to benefit outcomes.
PMID- 9649090
TI - Preterm contractions in community settings: II. Predicting preterm birth in women
with preterm contractions.
AB - OBJECTIVE: To examine risk factors for preterm delivery in women who present to
nontertiary care hospitals with preterm contractions. METHODS: Women who
presented to a network of community hospitals in Wisconsin with preterm
contractions were followed until delivery. The main outcomes were preterm
delivery before completion of 36 weeks of gestation and delivery within 1 week of
initial presentation. RESULTS: Of the 266 women presenting with contractions over
the 2-year study period, 90% (n=239) consented to participate. Multiple factors
were associated with premature delivery, but when examined with a multivariate
model, only four (ruptured membranes, multiple gestation, cervical effacement at
least 80%, and nonwhite race) were associated with prematurity, whereas five
(ruptured membranes, multiple gestation, cervical effacement at least 80%,
dilation exceeding 1 cm, and being a nonsmoker) predicted delivery within 1 week.
A decision model that combined the presence of ruptured membranes and effacement
at least 80% could predict delivery at 34 weeks or less within 7 days of
presentation with a sensitivity of 71% and a specificity of 98%. CONCLUSION: Only
two clinical cues (ruptured membranes and effacement of the cervix of 80% or
more) can predict premature delivery within 7 days. If these results are
confirmed prospectively, women with either of these signs could be targeted for
administration of steroids, antibiotics, or transfer to tertiary care facilities.
PMID- 9649091
TI - Elective induction versus spontaneous labor: a case-control analysis of safety
and efficacy.
AB - OBJECTIVE: To investigate the incidence, efficacy, and safety of elective
induction in a community teaching hospital over 1 year. METHODS: This is a
retrospective case-control study of rate, safety, and efficacy of all term
inductions with vertex presentations judged to be elective by chart analysis.
Cases were matched one for one for age, parity, and pay status with controls in
spontaneous labor. The elective induction women were compared with those in
spontaneous labor using chi2 Student t test, and Fisher exact test. Potential
risk factors for cesarean delivery and neonatal intensive care unit (NICU)
admission were then selected and subjected to bivariate analysis. Stepwise
logistic regression was applied to control for confounding and to select which
risk factors were important for those end points. RESULTS: There were 461 case
control pairs. The elective induction rate was 12.3%. Cesarean delivery was
increased by elective induction in bivariate analysis (odds ratio [OR]=1.81,
confidence interval [CI]=1.07, 3.08; power=.60). The cesarean delivery rate was
8.7% (control 5.0%). In a multiple regression model of potential risk factors for
cesarean delivery, nulliparity (OR=6.14, CI=2.90, 13.04), cervical priming
(OR=3.06, CI=1.46, 6.40), oxytocin usage (OR=2.82, CI=1.03, 7.75), gestational
age at least 287 days (OR=2.51, CI=1.38, 4.58), and birth weight at least 3800 g
(OR=2.29, CI=1.27, 4.13) were significant, but elective induction and epidural
anesthesia were not. Elective induction did not significantly increase the rate
of NICU admission (4.6% versus control 3.9%). In a multiple regression model of
potential factors predicting NICU admission, only a 5-minute Apgar score of at
most 8 was significant (OR = 12.34, CI=6.01, 25.3). CONCLUSION: Elective
induction is commonly practiced, safe, and efficacious. Cesarean delivery is
increased significantly by nulliparity and/or an unfavorable cervix, among other
factors, but not by elective induction itself.
PMID- 9649092
TI - Association of sociodemographic variables with risk for very preterm birth in
twins.
AB - OBJECTIVE: To assess the influence of maternal race, age, marital status, and
education on risk for earlier and later preterm births in twin pregnancies.
METHODS: We analyzed 8109 white and 1906 black liveborn twin pregnancies in the
Missouri Linked Sibship files for the years 1978-1990, using contingency tables
and multiple logistic regression. RESULTS: Black twin gestations had 1.61-fold
(95% confidence interval [CI] 1.46, 1.76) greater risk than whites for preterm
birth before 34 weeks' gestation. However, there was no race difference after 33
weeks. Among whites, teen age, unmarried status, and education fewer than 12
years were independently associated with risk for delivery before 34 weeks in
multivariate analysis (odds ratios [OR] 1.28-1.51, each P < or=.001). These
associations were diminished or absent for preterm births after 33 weeks'
gestation. White unmarried teen mothers with fewer than 12 years of education had
1.83-fold (95% CI 1.39, 2.40) greater risk for preterm birth before 34 weeks'
gestation compared with white married women more than 19 years of age with at
least 12 years of education. In blacks, this difference was 1.47-fold (95% CI
1.13, 1.92). In both races, these differences were absent after 33 weeks'
gestation. CONCLUSION: Traditional sociodemographic risk factors were present for
twin preterm birth, but mainly before 34 weeks' gestation. This, together with
previous data from Missouri Linked Sibship files, indicates that dominant
pathogenic mechanisms of early preterm birth in twin gestations are likely to be
different from those causing later preterm twin birth. Therefore, gestational age
should be accounted for in future studies seeking to identify predictive factors
or biomechanisms for twin preterm birth.
PMID- 9649093
TI - Fetal growth restriction at term: myth or reality?
AB - OBJECTIVE: To evaluate the morbidity and mortality associated with the small for
gestational age (SGA) fetus born at term to an otherwise uncomplicated pregnancy.
METHODS: Small for gestational age, singleton newborns (birth weight below the
tenth percentile for gestational age) born at 37-42 weeks' gestation were
identified by medical record discharge coding. We excluded gestations complicated
by structural or chromosomal abnormalities, maternal diabetes mellitus,
preeclampsia, chronic hypertension, asthma, or renal, endocrine, or autoimmune
disease. Three low-risk, appropriate for gestational age (AGA) fetuses, matched
for gestational age at delivery, were selected randomly for each SGA fetus and
served as controls. Maternal and neonatal data were abstracted via medical record
review. Statistical analysis included chi2 Fisher exact test, and analysis of
variance. RESULTS: There were 67 newborns in the study group and 201 in the
control group. There were no fetal or neonatal deaths in any of these cases. The
maternal age at delivery, prepregnancy weight, race, smoking status, weight gain
during pregnancy, and neonatal gender did not statistically differ between the
two groups. Compared with AGA infants, a larger proportion of SGA newborns had
low 1-minute Apgar scores and SGA newborns were more likely to be admitted to the
neonatal intensive care unit, and have respiratory distress, hypoglycemia,
thrombocytopenia, and hyperbilirubinemia. They were also significantly more
likely to be delivered by cesarean. CONCLUSION: The SGA newborn from an
uncomplicated pregnancy delivered at term has increased neonatal morbidity
compared with its AGA counterpart. These results dispute the notion that term
growth restriction is a benign condition.
PMID- 9649094
TI - Elevated umbilical cord plasma erythropoietin levels in prolonged pregnancies.
AB - OBJECTIVE: To determine if umbilical cord plasma erythropoietin levels are
elevated in pregnancies that continue beyond their expected date for delivery.
METHODS: Erythropoietin was measured using an enzyme-linked immunosorbent assay
in 124 appropriately grown newborns delivered from 37-43 weeks' gestation. Each
woman had an uncomplicated labor and delivery course without evidence of fetal
stress or meconium. The comparison was made between pregnancies ending at 37-40
weeks' gestation and those at 41-43 weeks' gestation. RESULTS: There was no
difference between the two groups in cord blood gases or Apgar scores at 1 and 5
minutes. Cord plasma erythropoietin levels were significantly higher in
pregnancies delivered after 41 completed weeks' gestation (41 or more weeks:
48.0+/-7.1 mIU/mL, n=45 versus 37-40 weeks: 26.1+/-4.2 mIU/mL, n=79, P < .001).
When compared with pregnancies delivered between 37 and 40 weeks, erythropoietin
levels were significantly elevated in pregnancies delivered at either 41, 42, or
43 weeks' gestation. CONCLUSION: In pregnancies reaching 41 weeks and beyond,
cord plasma erythropoietin levels are significantly increased, indicating altered
fetal oxygenation in some of these pregnancies. These results support the current
practice of close fetal surveillance of prolonged pregnancies.
PMID- 9649095
TI - Amniocentesis-related fetal loss: a cohort study.
AB - OBJECTIVE: To assess the risk of fetal loss attributable to second-trimester
amniocentesis. METHODS: A cohort study was undertaken among singleton pregnant
women undergoing genetic amniocentesis and controls matched prospectively on a
one-to-one basis, matched strictly for maternal age, parity, and socioeconomic
status. Both groups were recruited at 15-24 weeks' gestation and observed until
delivery. The fetal loss rates of the groups were compared. RESULTS: A total of
2256 pairs were recruited to the study. After excluding those pairs lost to
follow-up, those with fetal malformation, and those later proven to have major
chromosomal abnormalities, 2045 matched pairs were compared by pregnancy
outcomes. There were no significant differences in fetal loss rates, premature
deliveries, or placental abruptions between the study and control groups (P >
.05). However, this study did not have enough statistical power to identify
differences of less than 1%. CONCLUSION: Second-trimester amniocentesis is
probably not associated with a greater fetal loss rate than that of matched
controls.
PMID- 9649096
TI - Fetal heart rate and nuchal translucency in detecting chromosomal abnormalities
other than Down syndrome.
AB - OBJECTIVE: To evaluate whether the combined use of fetal heart rate (FHR) and
nuchal translucency measurements would be useful in the prediction of fetal
chromosomal abnormalities at 10-13 weeks' gestation. METHODS: In a prospective
study, 1053 (553 reported previously) consecutive singleton pregnancies between
10 and 13 weeks' gestation underwent chorionic villus sampling at our
institution. Fetal heart rate and fetal nuchal translucency thickness were
measured immediately before the invasive procedure. RESULTS: Thirty-five abnormal
karyotypes were diagnosed, including 17 trisomy 21, seven trisomy 18, one trisomy
13, one trisomy 9, four unbalanced translocation, two Klinefelter syndrome, one
Turner syndrome, one deletion of chromosome 18, and one true mosaicism. Using 95%
of normal ranges as the cutoff for both measurements, the detection rate for all
chromosomal anomalies was 77.1%, with a false-positive rate (1-specificity) of
7.7%, a positive predictive value of 25.7%, and a negative predictive value of
99.2%. Fetal heart rate improved the sensitivity of nuchal thickness in trisomies
21 and 18 (from 62.5% to 75%) and was particularly useful to detect other
chromosomal anomalies (from 27.2% to 81.8%). CONCLUSION: Our findings suggest
that there is an added role of FHR in ultrasound screening of chromosomal
abnormalities, specifically for those other than trisomy 21 and 18. The value of
a single measurement of fetal heart rate for screening purposes needs to be
confirmed by further investigation in a low-risk population.
PMID- 9649097
TI - Amniotic fluid complement C3 as a marker of intra-amniotic infection.
AB - OBJECTIVE: To determine the value of amniotic fluid (AF) complement C3 as a
marker of intra-amniotic infection and to compare complement C3 with other rapid
markers of intra-amniotic infection. METHODS: One hundred four women with
singleton gestations, in preterm labor with intact membranes, at 23-35 weeks'
gestation underwent transabdominal amniocentesis. Amniotic fluid was analyzed for
white blood cell (WBC) count, lactate dehydrogenase (LDH), glucose, Gram stain,
and complement C3. Cultures for aerobes, anaerobes, and mycoplasma species also
were performed. The median values of complement C3, WBC, LDH, and glucose were
compared between the culture-positive and -negative groups. Complement C3 was
compared with WBC count, LDH, glucose, and Gram stain for sensitivity,
specificity, positive and negative predictive values, and accuracy in the
prediction of a positive AF culture. Descriptive statistics, receiver operating
characteristic curve, Fisher exact test, and Wilcoxon rank-sum test were used for
analysis. RESULTS: The prevalence of positive cultures was 11.5% (12 of 104). The
culture-positive group had a significantly higher median C3 (7.0 mg/dL) than the
median C3 (3.0 mg/dL) of the culture-negative group (P < .001). Also, the median
values of WBC (1120.5 cells/mm3) and LDH (2697 U/L) were significantly higher and
the median glucose (6.5 mg/dL) was significantly lower among women with positive
AF cultures than among women with negative AF cultures (WBC=1 cell/mm3; LDH=165
U/L; glucose=45 mg/dL; P < .001). Eleven of the 12 culture-positive cases had a
C3 of 5 mg/dL or more, whereas four of the 92 culture-negative cases had a C3 of
5 mg/dL (P < .001). Nine of the 12 culture-positive cases but none of the 92
culture-negative cases had a C3 of 6 mg/dL or more (P < .001). The relative risks
of a positive AF culture were 65.27 (95% confidence interval [CI] 9.08, 469.27)
and 31.67 (95% CI 10.40, 96.43) times greater among women with AF complement C3
levels of 5 and 6 mg/dL or more, respectively. Depending on the cutoff point
used, complement C3 had similar or higher sensitivity, specificity, positive
predictive value, and negative predictive value for intra-amniotic infection when
compared with WBC count, LDH, glucose and Gram stain. CONCLUSION: Amniotic fluid
complement C3 has value in the diagnosis of intra-amniotic infection in preterm
labor with intact membranes. Complement C3 is available readily and compares
favorably with other rapid markers of AF infection. This study supports the
general concept of fetal inflammatory response to microbial invasion of AF.
PMID- 9649098
TI - Isolation of Ureaplasma urealyticum from the amniotic cavity and adverse outcome
in preterm labor.
AB - OBJECTIVE: To determine the relationship between the presence of Ureaplasma
urealyticum in the amniotic cavity and adverse maternal and perinatal outcome in
women with preterm labor. METHODS: Amniocentesis was performed in 181 patients
with preterm labor and intact membranes. Amniotic fluid (AF) was cultured for
aerobic and anaerobic bacteria and mycoplasmas. Patients were divided into three
groups according to the results of AF culture: those with negative AF cultures
(n=160), those with positive AF cultures and in whom the only microbial isolate
was U urealyticum (n=11), and those with positive cultures for non-ureaplasmas or
mixed microorganisms (n=10). Survival techniques were used for analysis. RESULTS:
The prevalence of positive AF cultures in which the only microbial isolate was
Uurealyticum was 6.1% (11 of 181), and of positive cultures with non-ureaplasmas
or mixed microorganisms was 5.5% (10 of 181). The amniocentesis-to-delivery
interval was significantly shorter in patients with positive cultures limited to
U urealyticum than in those with negative cultures (median 7 [range 0.1-149]
hours versus median 264 [0.1-2659] hours, P < .001). Preterm delivery within 48
hours, 72 hours, and 7 days was more frequent in patients with U urealyticum in
the AF than in those with sterile AF (48 hour: 91% versus 33%; 72 hour: 91%
versus 36%; 7 days: 100% versus 45%, P < .001 for each). Patients with positive
AF cultures limited to U urealyticum had a significantly higher rate of adverse
perinatal outcome than those with negative culture. Adverse outcomes included low
gestational age at birth, low birth weight, histologic chorioamnionitis,
significant neonatal morbidity, and perinatal death. CONCLUSION: Microbial
invasion of the amniotic cavity with U urealyticum is a risk factor for impending
preterm delivery and adverse perinatal outcome.
PMID- 9649099
TI - Invasive cervical cancer in human immunodeficiency virus-infected and uninfected
hospital patients.
AB - OBJECTIVE: To compare the prevalence of invasive cervical cancer in women with,
and in women without, human immunodeficiency virus (HIV) infection, so as to
evaluate the inclusion of invasive cervical cancer in the AIDS surveillance case
definition. METHODS: The Sentinel Hospital Surveillance System for HIV Infection
collected data and serum specimens that remained after clinical testing of
persons who received inpatient or outpatient care at 14 hospitals with high HIV
prevalence. We analyzed data on invasive cervical cancer obtained from medical
record review and HIV serostatus from white, black, and Hispanic women in the age
groups 20-34, 35-44, and 45-54 years. RESULTS: In 1994 and 1995, 2684 (6.6%) of
the 40,524 women sampled were HIV infected. Of the HIV-positive women, 28 had
invasive cervical cancer (10.4 per 1000 women) and of the HIV-negative women, 236
had invasive cervical cancer (6.2 per 1000 women, relative risk [RR] 1.7, 95%
confidence interval [CI] 1.1, 2.5). The prevalence of invasive cervical cancer
was higher for HIV-positive than for HIV-negative black women aged 20-34 (RR 3.8;
CI 1.7, 8.5) and Hispanic women aged 20-34 (RR 7.3; CI 1.4, 37.1) and 35-44 (RR
3.9; CI 1.1, 14.7) years. Twenty-six of the 28 cases of invasive cervical cancer
in HIV-positive women were in women known to be HIV-positive during admission.
CONCLUSION: The prevalence of invasive cervical cancer was higher for women who
were HIV positive than for women who were HIV negative. This lends support to the
inclusion of invasive cervical cancer in the revision of the surveillance case
definition for AIDS in 1993.
PMID- 9649100
TI - Oncogene expression: long-term compared with short-term survival in patients with
advanced epithelial ovarian cancer.
AB - OBJECTIVE: To determine if oncogene overexpression in patients with advanced
epithelial ovarian cancer correlates with survival. METHODS: Twenty-two women
with stage III ovarian cancer, observed for a median of 66 (range 48-204) months
were compared with 30 with a median survival of 18 (range 2-28) months. Using
immunocytochemistry, tumors were immunostained for overexpression of p53, c-erb-B
2, and epidermal growth factor receptor and were evaluated quantitatively for
expression of estrogen receptor, progesterone receptor, and Ki-67 antigen, a
marker of cellular proliferation. RESULTS: The median age of long-term survivors
was 52 (range 30-76) years compared with 55 (range 36-80) years for short-term
survivors. Optimal cytoreduction was achieved in 11 of the 22 long-term survivors
compared with seven of the 30 short-term survivors, a significant difference
(P=.05). The average level of Ki-67 expression was 43% in long-term survivors and
64% in short-term survivors (P=.007). Overexpression of p53 was seen in 54% of
long-term survivors and 80% of short-term survivors (P=.05). A combination of Ki
67 level of 50% or greater plus p53 overexpression was seen in 22% of long-term
survivors compared with 68% of short-term survivors (P=.005). Epidermal growth
factor receptor, c-erb-B-2, estrogen receptor, and progesterone receptor statuses
did not differ significantly between the two groups. CONCLUSION: Markers that did
not correlate with survival included the hormone receptors, estrogen receptor and
progesterone receptor, and the oncogenes, c-erb-B-2 and epidermal growth factor
receptor. Long-term survivors with advanced ovarian cancer were more likely to
have had an optimal cytoreduction and lower levels of Ki-67 antigen expression
and were less likely to overexpress p53 than were short-term survivors.
PMID- 9649101
TI - A randomized controlled trial of early postoperative feeding in gynecologic
oncology patients undergoing intra-abdominal surgery.
AB - OBJECTIVE: To evaluate the safety and efficacy of early oral feeding after intra
abdominal surgery in gynecologic oncology patients. METHODS: During a 1-year
period, 200 gynecologic oncology patients undergoing intra-abdominal surgery were
enrolled in a randomized controlled trial of early compared with traditional oral
postoperative feeding. Patients allocated to early postoperative oral feeding
began a clear liquid diet on the first postoperative day and then advanced to a
regular diet as tolerated. Patients allocated to traditional postoperative oral
feeding received nothing by mouth until return of bowel function (defined as the
passage of flatus in the absence of vomiting or abdominal distention), then began
a clear liquid diet, and advanced to a regular diet as tolerated. RESULTS: Age,
case distribution, surgery length, blood loss, and first passage of flatus were
similar in the early and traditional feeding groups. Significantly more patients
in the early group developed nausea. Despite this, the incidence of vomiting,
abdominal distention, incidence and duration of nasogastric tube use, and
percentage of patients who tolerated clear liquid and regular diets on the first
attempt were comparable in both groups. Time to development of bowel sounds, time
to initiation of clear liquid and regular diets, and hospital stay were
significantly longer in the traditional group. Major complications (eg,
pneumonia, atelectasis, and wound complications) and febrile morbidity occurred
equally in both groups. There were no known anastamotic complications or
aspirations in either group. Postoperative changes in hematologic indices and
electrolytes were comparable in both groups. CONCLUSION: Early postoperative
feeding in gynecologic oncology patients undergoing intra-abdominal surgery is
safe and well tolerated.
PMID- 9649102
TI - Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter
comparison.
AB - OBJECTIVE: To compare the clinical efficacy and safety of a thermal uterine
balloon system with hysteroscopic rollerball ablation in the treatment of
dysfunctional uterine bleeding. METHODS: Two hundred fifty-five premenopausal
women were treated in a randomized multicenter study comparing thermal uterine
balloon therapy with hysteroscopic rollerball ablation for the treatment of
menorrhagia. Preprocedural and postprocedural menstrual diary scores and quality
of-life questionnaires were obtained. Twelve-month follow-up data are presented
on 239 women. RESULTS: Twelve-month results indicated that both techniques
significantly reduced menstrual blood flow with no clinically significant
difference between the two groups as reflected by return to normal bleeding or
less (balloon 80.2% and rollerball ablation 84.3%). Multiple quality-of-life
questionnaire results were also similar, including percent of patients highly
satisfied with their results (balloon 85.6% compared with rollerball 86.7%). A
90% decrease in diary scores was seen in more than 60% of patients in both
groups. Procedural time was reduced significantly in the uterine balloon therapy
group. Intraoperative complications occurred in 3.2% of the hysteroscopic
rollerball patients, whereas no intraoperative complications occurred in the
thermal balloon group. CONCLUSION: In the treatment of dysfunctional uterine
bleeding, uterine balloon therapy is as efficacious as hysteroscopic rollerball
ablation and may be safer.
PMID- 9649103
TI - Tumor growth and dissemination after laparotomy and CO2 pneumoperitoneum: a rat
ovarian cancer model.
AB - OBJECTIVE: To compare tumor growth, intraperitoneal implantation, and abdominal
wall metastasis after laparotomy and CO2 pneumoperitoneum in a rat ovarian cancer
model. METHODS: To mimic intraoperative rupture of an ovarian tumor in a syngenic
rat ovarian carcinoma model, 10(5) malignant cells were injected
intraperitoneally after a 5-cm vertical midline laparotomy or after the
insufflation of a CO2 pneumoperitoneum achieved with 4 mmHg or 10 mmHg intra
abdominal pressure. Two weeks later, the intraperitoneal tumor growth and the
tumor dissemination were evaluated semiquantitatively with a scoring system. The
scores attributed to each organ were added to calculate the dissemination score
of each animal. RESULTS: The mean (+/-SD) dissemination score was 83.4+/-12 in
the laparotomy group and 67.3+/-16 and 71.9+/-17 in the 4 and 10 mmHg CO2
pneumoperitoneum groups, respectively (P < .01). The scores for the peritoneum
were 21.8+/-3.8 in the 10 mmHg pneumoperitoneum group and 18+/-2.4 in the
laparotomy group (P < .01). In the laparotomy group, the implant found along the
midline scar accounted for a mean of 62.6+/-15% of the peritoneal score, whereas
the trocar site metastases did not influence the peritoneal score in the
pneumoperitoneum groups. The incidence of wound metastasis was 96% in the
laparotomy group and 55% and 54% in the 4 mmHg and 10 mmHg pneumoperitoneum
groups, respectively. CONCLUSION: In this model, tumor growth was greater after
laparotomy than after laparoscopy, but peritoneal tumor dissemination was more
severe after CO2 pneumoperitoneum.
PMID- 9649104
TI - Comparison of bimanual examination with ultrasound examination before
hysterectomy for uterine leiomyoma.
AB - OBJECTIVE: To correlate the preoperative bimanual examination with ultrasound
examination with regard to estimating the size of enlarged nongravid
leiomyomatous uteri. METHODS: We performed a retrospective review of 161 patients
who underwent hysterectomy for uterine leiomyoma between January 1994 and
December 1994 and between July 1995 and April 1996. Uterine size was estimated
clinically by bimanual examination. Ultrasound reports were reviewed. Uterine
weights and dimensions in pathology reports were compared with findings on
bimanual examination and ultrasonography. Body mass index (BMI) was calculated
and patients were divided into two groups, one with BMIs of more than 30 and
another with BMIs of less than or equal to 30. RESULTS: Ultrasound examination
was ordered in 111 patients (68.9%) preoperatively. There was a strong
correlation between the bimanual examination findings and the ultrasound
dimensions. The equation for this relationship is ultrasound length (cm)=3.68 +
0.68 x number of weeks (r=.78, P < .001). Ultrasound length also was related
strongly to size given in the pathologic reports; the equation for this
relationship is ultrasound length (cm)=2.94 + 0.75 x pathology length (cm)
(r=.73, P < .001). The correlation between bimanual examination and ultrasound
findings was similar in obese and in nonobese patients, when uterine size could
be estimated. CONCLUSION: There is a strong correlation between bimanual and
ultrasound examinations with regard to determining the size of leiomyomatous
uteri. Routine ultrasound is not indicated when an experienced examiner can
assess uterine size. Ultrasonography may be appropriate when physical assessment
is difficult, as in the case of obesity.
PMID- 9649105
TI - Urinary tract injuries after hysterectomy.
AB - OBJECTIVE: To evaluate the nationwide incidence and characteristics of urinary
tract injuries after laparoscopic hysterectomy, total abdominal hysterectomy,
supracervical abdominal hysterectomy, and vaginal hysterectomy. METHODS: We
analyzed retrospectively 142 urinary tract injuries after hysterectomy, reported
to the National Patient Insurance Association in Finland from 1990 through 1995.
The Finnish Hospital Discharge Register collects data on procedures from all
hospitals, and 62,379 hysterectomies were carried out during the study period.
RESULTS: The total incidence of ureteral injury after all hysterectomies was 1.0
of 1000 procedures: 13.9 of 1000 after laparoscopic, 0.4 of 1000 after total
abdominal, 0.3 of 1000 after supracervical abdominal, and 0.2 of 1000 after
vaginal hysterectomy. Difficulties during an operation with a ureteral injury
were encountered in 51%, 76%, 100%, and 100%; the failure rates of primary repair
of a ureteral injury were 5%, 12%, 0%, and 0%; and the convalescence times after
a ureteral injury were 86 days, 94 days, 71 days, and 47 days after laparoscopic,
abdominal, supracervical abdominal, and vaginal hysterectomies, respectively. The
incidence of bladder injury was 1.3 of 1000 procedures. Sixty-five percent of
reported bladder injuries were fistulas, giving an incidence of vesicovaginal
fistula of 0.8 of 1000 procedures after all hysterectomies: 2.2 of 1000 after
laparoscopic, 1.0 of 1000 after total abdominal, 0 of 1000 after supracervical
abdominal, and 0.2 of 1000 after vaginal hysterectomy. Difficulties during an
operation with a bladder injury were encountered in 53%, 37%, 100%, and 0%; the
failure rates of primary repair of a simple bladder injury were 5%, 18%, 0%, and
0%; the failure rates of primary repair of a vesicovaginal fistula were 17%, 20%,
0%, and 0%; and the convalescence times after a bladder injury were 51 days, 118
days, 71 days, and 99 days after laparoscopic, abdominal, supracervical
abdominal, and vaginal hysterectomy, respectively. CONCLUSION: The risk of
ureteral injury is higher after laparoscopic hysterectomy compared with
traditional hysterectomies.
PMID- 9649106
TI - Prognostic validity of neoplastic cells with notable nuclear atypia in
endometrial cancer.
AB - OBJECTIVE: To investigate how the architectural grade of endometrial
adenocarcinoma should be adjusted in the presence of neoplastic cells with
notable nuclear atypia in order to assign the histologic grade. METHODS: Four
hundred seventy-six patients with stage I endometrial cancer (endometrioid type)
who were surgically treated in a single institute formed the study population.
The architectural grade and the proportion of tumor cells with notable nuclear
atypia were examined for each case. The effects of notable nuclear atypia on the
disease-free survival of each architectural grade were analyzed. RESULTS: The
disease-free survival of architectural grade 1 and grade 2 tumors was
significantly affected and was worse than that of architectural grade 3 tumors
when more than 25% of the tumor cells showed notable nuclear atypia. Tumors that
had 26% to 50% of neoplastic cells with notable nuclear atypia showed a similar
probability of recurrence as did tumors that had more than 50% of neoplastic
cells with notable nuclear atypia. CONCLUSION: The series suggests that the
upgrading of architectural grade 1 or 2 tumors, in which more than 25% of the
neoplastic cells show notable nuclear atypia, into a grade 3 tumor may be more
practical than upgrading by one architectural grade 1 or 2 tumors, in which the
majority of neoplastic cells show notable nuclear atypia.
PMID- 9649107
TI - Cytology and colposcopy after loop electrosurgical excision: implications for
follow-up.
AB - OBJECTIVE: To analyze risk factors associated with residual and recurrent lesions
after loop electrosurgical excision procedure and to assess the reliability of
cytology and colposcopy in detection of these lesions. METHODS: Cytology and
colposcopy were used to follow up 288 women after treatment by loop
electrosurgical excision 3-6 months, 9-15 months, and 24-36 months after the
procedure. RESULTS: The mean (+/-standard deviation) postoperative follow-up was
39+/-13 months (range 24-68 months). Treatment failure, defined as the
persistence or recurrence of a cervical lesion, was observed in 20 patients
(6.9%). The endocervical localization of the initial lesion (adjusted relative
risk [RR] 13.7; 95% confidence interval [CI] 1.3, 150.1; P < .05) and incomplete
excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < .001) were the only independent
risk factors for treatment failure. In six cases, a second treatment was
performed before the first cytologic and colposcopic visit because of incomplete
excisions. The remaining 14 treatment failures were diagnosed by postoperative
cytology and colposcopy, ten after the first visit, three after the second, and
one after the third. To diagnose the treatment failures, colposcopy and cytology
provided complementary information at the first (P < .001) and second
postoperative visits (P < .05). Although the sensitivity of cytology was not
significantly improved by the association of both methods, the latter decreased
the number of residual lesions overlooked by cytology alone and contributed to
the diagnosis of 95% of treatment failures in less than 2 years. CONCLUSION: The
high detection rate obtained by combining cytology and colposcopy during the
first 2 postoperative years may allow more leisurely follow-up schedules after
that time and may reduce the consequences of subsequent loss to follow-up.
PMID- 9649108
TI - The use and failure rates of protective equipment to prevent blood and bodily
fluid contamination in the obstetric health care worker.
AB - OBJECTIVE: To determine the frequency of use and the failure rate of protective
equipment by obstetric staff during common obstetric procedures. METHODS: A
prospective observational study was conducted of multiple obstetric procedures.
The presence, area of specialty, level of training, and gender of each team
member were recorded along with the use of protective equipment (cap, mask,
eyewear, gown, gloves, and shoe protection). These observations were recorded by
two trained observers. Blood and bodily fluid contamination of the protective
equipment was quantified and recorded for each person. A forensic medicine
reagent (Luminol; Cluefinders Inc., Tampa, FL) was used to detect trace amounts
of blood on the inner surface of a selected subset of gowns that had gross
external contamination but no obvious penetration. RESULTS: Two hundred forty-one
obstetric procedures were observed involving 1022 medical personnel. The use of
at least one piece of protective equipment was noted 88% of the time. Compliance
with universal precautions by attending and resident physicians in all deliveries
(vaginal, forceps, vacuum, cesarean) was observed in 65 (25.2%) medical
personnel. The use of protective equipment varied by the type of procedure, area
of specialty, and level of training of the team member. In the gowns examined
with the forensic medicine reagent, 44% of the cases demonstrated laboratory
evidence of penetration. The frequency of gown failure varied with the type of
surgical gown used. CONCLUSION: Despite the mandate in the medical community for
universal precautions, the rate of compliance remains low. However, even among
the compliant medical staff, protective equipment labeled as impenetrable has a
high failure rate.
PMID- 9649109
TI - Effect of maternal hydration on fetal renal pyelectasis.
AB - OBJECTIVE: To assess the effect of maternal hydration on fetal pyelectasis.
METHODS: Thirteen pregnant women with fetal pyelectasis and 13 controls matched
for gestational age were recruited during the same period. Ultrasound and Doppler
studies and maternal urine specific gravity measurements were carried out before
and after maternal oral hydration. The data were analyzed by either a two- or
three-factor analysis of variance. RESULTS: Renal artery Doppler pulsatility
index was significantly greater in the study group than in the controls (2.37
versus 1.83; P=.009) and this finding was unaffected by maternal hydration
status. After hydration, the maternal urinary specific gravity decreased
significantly (1.018 versus 1.009; P < .001), the amniotic fluid index (AFI)
increased significantly (14.27 versus 18.24 cm; P < .001), and the fetal renal
pelvis diameter increased significantly (0.29 versus 0.46 cm; P=.002) in both the
study and control groups. Renal pelvis anteroposterior diameter after hydration
did not differ significantly whether the fetal bladder was full or empty (0.7
versus 0.6 cm; P=.1). In this study, each subject served as her own control (ie,
from before to after hydration). Three of 13 controls met the diagnostic criteria
for pyelectasis after maternal hydration. CONCLUSION: The AFI increases after
maternal hydration in both normal fetuses and those with pyelectasis. The fetal
renal pelvis anteroposterior diameter increases with maternal hydration in both
normal fetuses and those with pyelectasis and is independent of the state of the
fetal bladder. The renal artery Doppler pulsatility index is significantly
greater in fetuses with pyelectasis than in controls.
PMID- 9649110
TI - Operational improvement of gynecologic laparoscopic operating room services: an
internal review.
AB - BACKGROUND: To reorganize reusable laparoscopic instrumentation to promote
instrument accessibility, minimize instrument breakage, eliminate infrequently
used instruments on permanent trays, and help control maintenance costs.
TECHNIQUE: The Robert Wood Johnson University Hospital Gynecologic Steering
Committee evaluated during a 5-month period the storage, use, and maintenance of
gynecologic laparoscopic instrument sets used in the surgical suite. Acting on
this data, the committee oversaw the following changes. Infrequently used
instruments were removed from permanent trays and separately packaged. Two types
of gynecologic laparoscopy trays were prepared: one for laparoscopic bilateral
tubal ligations and one for both diagnostic and operative laparoscopy. A double
decker compartmentalized tray in which instruments were sterilized and stored
replaced the extant single-layer ones in which instruments were stacked on each
other. To facilitate instrument identification and function, a surgical manual
was compiled with photographs of each instrument and a description of its use.
EXPERIENCE: After implementation of these changes, maintenance and sterilization
costs for a 10-month period were compared with those for the previous 10 months.
There was a savings of $13,889. The ratio of total costs divided by number of
cases performed during the two study periods was also compared. There was a
savings of $31 per case. CONCLUSION: Savings were achieved by reorganizing this
operating room's handling of reusable gynecologic laparoscopy equipment. By
eliminating infrequently used instruments from the permanent trays and by using a
double decker compartmentalized tray that was used during surgery, sterilization,
and storage, both sterilization costs and maintenance costs were reduced.
PMID- 9649111
TI - The Gupta-Frank clamp for salpingo-oophorectomy at vaginal hysterectomy.
AB - BACKGROUND: When performing a vaginal hysterectomy, removal of the tubes and
ovaries can be either necessary or desirable. We describe our experience with a
new instrument called the Gupta-Frank clamp for performing vaginal salpingo
oophorectomy at the time of vaginal hysterectomy. INSTRUMENT: The stainless steel
Gupta-Frank clamp is 260 mm long, and its shanks are curved to avoid impedance
from the vaginal walls. The 70-mm jaws have a smooth curve, which allows both the
round and infundibulopelvic ligaments to be incorporated into a single clamp
bite. Each jaw has three serrated grooves, which interlock with the corresponding
jaw grooves to give a 6-mm-wide atraumatic nonslip area. EXPERIENCE: We have used
this instrument in 18 women undergoing bilateral salpingo-oophorectomy at the
time of vaginal hysterectomy. A single clamp bite on each side was sufficient to
accomplish salpingo-oophorectomy in all cases. There were no major complications.
CONCLUSION: Salpingo-oophorectomy performed vaginally at the time of vaginal
hysterectomy with the Gupta-Frank clamp is feasible and is accomplished easily
and safely.
PMID- 9649112
TI - A comprehensive resident training program in operative endoscopy.
AB - We describe a structured and uniform resident experience in operative endoscopy
and analyze the costs of implementing such a program at an urban academic medical
center. The residency curriculum at Northwestern Memorial Hospital incorporates a
five-part approach to endoscopy training: weekly endoscopy rounds, an annual
animal laboratory for residents, an individual animal laboratory, supervision by
skilled endoscopic surgeons, and a laparoscopic training facility. Thirty-two
residents have completed the training over 4 years. The annual cost of the entire
program is $34,500, which can be offset partially by vendor support. A
comprehensive and continuous endoscopic training program is an important and
affordable part of resident education.
PMID- 9649113
TI - Prediction of preterm delivery by fetal fibronectin: a meta-analysis.
AB - OBJECTIVE: To assess the cervicovaginal fetal fibronectin test to predict preterm
delivery. DATA SOURCES: We searched MEDLINE, Current Contents, Index Medicus, and
proceedings of meetings for studies published between 1991 and June 1997. METHODS
OF STUDY SELECTION: Inclusion criteria were prospective cohort study; test
performed between 20 and 36 weeks' gestation; fetal fibronectin measured by a
previously described assay, with a cutoff level set at 50 ng/mL; test results not
disclosed to women or physicians; and fewer than 20% of study participants
excluded from the analysis. TABULATION, INTEGRATION, AND RESULTS: Twenty-nine
relevant studies were stratified according to the prevalence of preterm delivery,
the number of tests performed, and delivery before 34, 35, or 37 weeks.
Sensitivities, specificities, and likelihood ratios were calculated in each
study. The summary estimates of the likelihood ratio for tests yielding positive
results or tests yielding negative results along with their 95% confidence
intervals (CIs) were computed in each stratum according to a random-effects
model. All summary likelihood ratios for a test yielding positive results
indicated a significant association with preterm delivery. The strongest
association was found between a single test with positive results and delivery
before 37 weeks in a low-risk population (likelihood ratio 7.5; 95% CI 4.6,
12.3). This association also was found in high-risk women (likelihood ratio 3.5;
95% CI 2.6, 4.6). In high-risk women, a test yielding negative results was
associated with a reduction in risk of preterm delivery (likelihood ratio 0.4;
95% CI 0.3, 0.5). CONCLUSION: Fetal fibronectin in cervicovaginal secretions is
associated with preterm delivery in both high-risk and low-risk women.
PMID- 9649114
TI - Correlates of postmenopausal female hormone use among black women in the United
States.
PMID- 9649115
TI - Toxicity to neuroblastoma cells and spheroids of benzylguanidine conjugated to
radionuclides with short-range emissions.
AB - Radiolabelled meta-iodobenzylguanidine (MIBG) is selectively taken up by tumours
of neuroendocrine origin, where its cellular localization is believed to be
cytoplasmic. The radiopharmaceutical [131I]MIBG is now widely used in the
treatment of neuroblastoma, but other radioconjugates of benzylguanidine have
been little studied. We have investigated the cytotoxic efficacy of beta, alpha
and Auger electron-emitting radioconjugates in treating neuroblastoma cells grown
in monolayer or spheroid culture. Using a no-carrier-added synthesis route, we
produced 123I-, 125I-, 131I- and 211At-labelled benzylguanidines and compared
their in vitro toxicity to the neuroblastoma cell line SK-N-BE(2c) grown in
monolayer and spheroid culture. The Auger electron-emitting conjugates
([123I]MIBG and [125I]MIBG) and the alpha-emitting conjugate ([211At]MABG) were
highly toxic to monolayers and small spheroids, whereas the beta-emitting
conjugate [131I]MIBG was relatively ineffective. The Auger emitters were more
effective than expected if the cellular localization of MIBG is cytoplasmic. As
dosimetrically predicted however, [211At]MABG was found to be extremely potent in
terms of both concentration of radioactivity and number of atoms ml(-1)
administered. In contrast, the Auger electron emitters were ineffective in the
treatment of larger spheroids, while the beta emitter showed greater efficacy.
These findings suggest that short-range emitters would be well suited to the
treatment of circulating tumour cells or small clumps, whereas beta emitters
would be superior in the treatment of subclinical metastases or macroscopic
tumours. These experimental results provide support for a clinical strategy of
combinations ('cocktails') of radioconjugates in targeted radiotherapy.
PMID- 9649116
TI - Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells
under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIA.
AB - We investigated the role of platelets in human melanoma cell (line 397)
interaction with vascular endothelial cells (ECs) under flow conditions. The
ability of the tumour cells to adhere to the EC monolayer was significantly
reduced by application of flow at a shear rate of 250 s(-1). A 2.2-fold increase
in tumour cell adhesion to ECs under flow was observed upon addition of thrombin
receptor agonist peptide (TRAP)-activated platelets but not resting platelets. A
similar increase (2.5-fold) in tumour cell adhesion to ECs under flow was
observed when the tumour cells were incubated with resting platelets on thrombin
treated ECs. However, thrombin treatment of the ECs alone had no effect on tumour
cell adhesion in the absence of platelets. The enhancement of tumour cell
adhesion to ECs by TRAP-activated platelets was virtually abolished by blockade
of the platelet glycoproteins P-selectin and GPIIb-IIIa by monoclonal antibodies.
Blockade of P-selectin also inhibited the direct adhesion of TRAP-activated
platelets to ECs, but did not affect the interaction of the tumour cells with
platelets immobilized on subendothelial extracellular matrix (ECM). Blockade of
GPIIb-IIIa inhibited both platelet-EC and platelet-tumor cell interactions. Our
results indicate that tumour cell adhesion to the endothelium under flow is
enhanced by platelets under conditions that allow platelet adhesion to ECs.
Inhibition studies suggest that activated platelet adhesion to ECs is mediated by
P-selectin and GPIIb-IIIA, and tumour cell adhesion to EC-bound platelets--mainly
by GPIIb-IIIa.
PMID- 9649117
TI - Amplification and expression of the ABC transporters ARA and MRP in a series of
multidrug-resistant leukaemia cell sublines.
AB - E1000, the most drug-resistant subline from the E-series (CCRF-CEM/E16 to E1000),
has been previously shown to express high mRNA levels from two ABC transporter
genes associated with multidrug resistance, ARA and MRP. The expression and
amplification of both genes has now been characterized for each member of the E
series of drug-resistant sublines and is reported here. Both ARA [detected by
reverse transcriptase polymerase chain reaction (RT-PCR)] and MRP (detected by
Northern blot analysis) were expressed at low levels in the sensitive parental
CEM cell line. An equivalent level of MRP mRNA expression was detected throughout
the CEM, E16, E25 and E50 sublines, and there was increasing expression in the
E100, E200 and E1000 sublines. ARA expression was not detected in the E16, E25,
E50 and E100 sublines but was detected by both RT-PCR and Northern blot analysis
in the E200 and E1000 sublines. Southern blot analysis indicated the increased
levels of MRP and ARA expression resulted from gene amplification and that MRP
was first amplified in the E100 subline and ARA in the E200 subline, suggesting
that the two genes were not initially co-amplified. Cytogenetic analysis of E1000
cells demonstrated a large addition to chromosome 16p, around the region where
the ARA and MRP genes are located. Increased expression of ARA is associated with
increased colchicine resistance in the E-series of sublines and combined with MRP
may account for their resistance phenotype.
PMID- 9649118
TI - Regulation of interferon responses in medulloblastoma cells by interferon
regulatory factor-1 and -2.
AB - Transcriptional activator interferon regulatory factor (IRF)-1 and repressor IRF
2 are known to play a critical role in the regulation of interferon (IFN)
responses and oncogenesis in fibroblasts. Although these two factors are
expressed in many tissues, including the brain, the role of IRFs in the central
nervous system (CNS) has not been elucidated. We analysed a medulloblastoma cell
line, ONS-76, as a CNS-derived model system and generated its derivatives, R1 and
R2 cells, which constitutively expressed each mouse IRF-1 and IRF-2 cDNA at high
levels. By viral infection, R1 and R2 cells showed IFN-beta gene expression 3 h
earlier than the control ONS-76 (C-76) cells, with 2.46- and 2.24-fold increase
in IFN-beta production respectively. In the presence of cycloheximide, virally
induced IFN-beta gene expression of C-76 cells was suppressed, whereas R1 and R2
cells produced IFN-beta 7.5- and 2.2-fold higher than C-76 cells respectively. On
the other hand, induction of IFN-inducible genes was enhanced in R1 cells but was
suppressed in R2 cells compared with C-76 cells. These results demonstrate that
IRF-1 and IRF-2 may play an important role in the regulation of IFN-beta and IFN
inducible genes and that IRF-2 may have dual functions as an activator and
repressor in CNS-derived cells.
PMID- 9649119
TI - Anti-proliferative activity and mechanism of action of titanocene dichloride.
AB - Development of resistance to cytotoxic agents is a major limitation to their
clinical use. Novel compounds are synthesized with a view to develop non-cross
resistant, less toxic and more potent activity. The detection of the anti-tumour
properties of the inorganic compound cisplatin stimulated a broad search for
other metal-containing complexes. Titanocene dichloride was synthesized on this
basis and has shown potent anti-neoplastic activity in experimental animals. We
have examined the in vitro activity of titanocene dichloride in two pairs of
platinum-sensitive and resistant human ovarian carcinoma cell lines, A2780/2780CP
and CH1/CH1cisR, and in mutated p53- and bcl-2-transfected clones of A2780 cells.
A time- and concentration-dependent anti-proliferative effect was observed in all
cell lines treated with titanocene dichloride. The drug was found to
significantly overcome platinum resistance in the 2780CP and the CH1 cisR cell
lines and in the bcl-2 and the mutant p53 transfectants of A2780 cells.
Titanocene dichloride induced a block in late S/early G2 phase of the cell cycle;
however apoptotic cell death occurred from any phase of cycle. Titanium-DNA
adducts were detected in A2780 cells treated with titanocene dichloride using
atomic absorption spectrometry, suggesting that DNA may be a target for this
drug. In agreement with this finding, p53 accumulated rapidly in drug-treated
A2780 cells, indicative of a role for titanocene dichloride as a DNA-damaging
agent. We have also performed studies to determine whether titanocene dichloride
could demonstrate synergy with other cytotoxic agents in vitro. Isobologram
analysis of cytotoxicity data obtained suggests that the combination of
titanocene dichloride and 5-fluorouracil (5-FU) is synergistic. The potent in
vivo anti-tumour activity of this compound, supported by the encouraging results
from two phase I clinical trials, suggests that titanocene dichloride could be a
promising novel chemotherapeutic agent.
PMID- 9649120
TI - Interstitial photodynamic therapy with the second-generation photosensitizer
bacteriochlorin a in a rat model for liver metastases.
AB - Bacteriochlorin a (BCA) is a second-generation photosensitizer that is effective
in tumour destruction upon illumination with light of a wavelength of 760 nm.
Tissue penetration by light at this wavelength is greater compared with
wavelengths at which commonly used photosensitizers are illuminated, making it
possible to treat larger tumours. In a model of experimental liver metastases in
rats, we measured lesion sizes after interstitial illumination of tumours at
different times after intravenous administration of BCA (10 mg kg(-1)
bodyweight), as well as BCA concentrations in liver and tumour tissue. In both,
BCA concentrations showed a rapid decline within the first 4 h, followed by a
slow decrease over the next 20 h, suggesting biphasic pharmacokinetics. No
selective uptake in tumour tissue was observed. A near-linear relationship was
found between lesion sizes and liver and tumour BCA concentrations, suggesting
that optimal results with photodynamic therapy (PDT) could be obtained by
illumination within a short time interval after administration, when tissue
concentrations are highest. No severe liver toxicity was observed as indicated by
serum ALAT levels. However, in all tumours evaluated, islands of vital-looking
cells were present leading to tumour regrowth within 35 days. In view of the
obtained lesion diameters of approximately 13 mm after BCA-PDT and the rapid
clearance rate of BCA, the concept of a near-infrared absorbing photosensitizer
for PDT of liver tumours is a potential interesting strategy.
PMID- 9649121
TI - Electrochemotherapy on liver tumours in rabbits.
AB - Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of
a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell
permeabilizing electric pulses (EPs) locally delivered to tumours. The transient
permeabilization of the cell membrane by the EPs allows free access of BLM to its
intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy
has been proved so far on transplanted subcutaneous murine tumours and on
subcutaneous metastases in humans. Here, we present the first study of the
effects of ECT on tumours transplanted to livers in rabbits. We used a recently
developed EP applicator consisting of an array of parallel and equidistant
needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed
by histological analysis, tumour growth rates and survival of the treated
animals. A transient blood hypoperfusion was seen in the electropulsed areas,
with or without BLM, related to EP-dependent vasoconstriction but this had no
major effects on cell survival. Long-term effects depended on the presence of BLM
at the time of EP delivery. Almost complete tumour necrosis was observed after
ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized
tumour cells and indirect effects on the tumour vessels. A large reduction in
tumour growth rate and significantly longer survival times were scored in
comparison with control rabbits. Moreover, ECT of liver tumours was well
tolerated and devoid of systemic side-effects. When ECT was associated with a
local interleukin 2-based immunotherapy, increased local anti-tumour
effectiveness as well as a large decrease in the number of metastases were
observed. Thus, ECT could become a novel treatment modality for liver tumours and
other solid internal malignancies.
PMID- 9649122
TI - Evaluation of a novel in vitro assay for assessing drug penetration into
avascular regions of tumours.
AB - The poor blood supply to solid tumours introduces many factors that affect the
outcome of chemotherapy, one of which is the problem of drug delivery to poorly
vascularized regions of tumours. Whereas poor drug penetration has been
recognized as a contributing factor to the poor response of many solid tumours,
the question of drug penetration through multicell layers has not been thoroughly
addressed, largely because of restrictions imposed upon these studies by the
requirement for either radiolabelled or naturally fluorescent compounds. The aim
of this study is to describe modifications made to a recently published assay
that broadens the scope for assessing drug penetration during the early stages of
drug development and to characterize the ability of various drugs to penetrate
multicell layers. DLD-1 human colon carcinoma cells were cultured on Transwell
COL plastic inserts placed into 24-well culture plates so that a top and bottom
chamber were established, the two chambers being separated by a microporous
membrane. Drugs were added to the top chamber at doses equivalent to peak plasma
concentrations in vivo and the rate of appearance of drugs in the bottom chamber
determined by high-performance liquid chromatography (HPLC). Both 3-amino-1,2,4
benzotriazine 1,4-dioxide (tirapazamine) and 7-[4'-(2-nitroimidazol-1-yl)-butyl]
theophylline (NITP) rapidly penetrated DLD-1 multicell layers (50.9 +/- 12.1
microm thick) with t(1/2) values of 1.36 and 2.38 h respectively, whereas the
rate of penetration of 5-aziridino-3-hydroxymethyl-1-methyl-2-[1H-indole-4,7
dione] prop-beta-en-alpha-ol (EO9) and doxorubicin through multicell layers was
significantly slower (t(1/2) = 4.62 and 13.1 h respectively). Inclusion of
dicoumarol increases the rate of EO9 penetration, whereas reducing the oxygen
tension to 5% causes a reduction in tirapazamine penetration through multicell
layers, suggesting that the extent of drug metabolism is one factor that
determines the rate at which drugs penetrate multicell layers. The fact that EO9
does not readily penetrate a multicell layer, in conjunction with its rapid
elimination in vivo (t(1/2) < 10 min), suggests that EO9 is unlikely to penetrate
more than a few microm from a blood vessel within its pharmacokinetic lifespan.
These results suggest that the failure of EO9 in the clinic is due to a
combination of poor drug penetration and rapid elimination in vivo.
PMID- 9649123
TI - Differential expression of vascular endothelial growth factor mRNA vs protein
isoform expression in human breast cancer and relationship to eIF-4E.
AB - Angiogenesis is the formation of new blood vessels from the existing vasculature.
Vascular endothelial growth factor (VEGF) is an endothelium-specific angiogenic
factor strongly implicated in pathological angiogenesis. In this study, the mRNA
and protein expression of the four alternatively spliced VEGF isoforms (121, 165,
189 and 206 amino acids) were examined in normal and malignant breast tissues.
Three VEGF transcripts were detected in both (121>165>189), whereas only VEGF165
protein was detected. The tumours expressed more VEGF mRNA (P = 0.02) and protein
(P < 0.0001), with eight-fold more VEGF protein generated per mRNA unit (P =
0.009). To examine this further, the expression of eIF-4E, a translation
initiation factor, was examined. Increased eIF-4E mRNA levels were detected in
the tumours (P < 0.0001) that correlated with VEGF mRNA (P = 0.0002), implying co
regulation of these genes. VEGF mRNA expression was elevated in tumours
expressing the epidermal growth factor receptor (P < 0.01), but there was no
difference according to oestrogen receptor status (P = 0.9), node status (P =
0.09) or between differing histologies (P = 0.4). These data suggest that
elevated VEGF protein expression, by both enhanced transcription and translation,
is a potential means by which tumour angiogenesis is induced in breast
carcinomas. VEGF expression is also significantly associated with factors
correlating with a poor outcome, implying a role in progression of this disease.
PMID- 9649124
TI - A sequential treatment regimen with melatonin and all-trans retinoic acid induces
apoptosis in MCF-7 tumour cells.
AB - Neoplastic events are marked by uncontrolled cell proliferation. One major focus
of cancer research has been to identify treatments that reduce or inhibit cell
growth. Over the years, various compounds, both naturally occurring and
chemically synthesized, have been used to inhibit neoplastic cell proliferation.
Two such oncostatic agents, melatonin and retinoic acid, have been shown to
suppress the growth of hormone-responsive breast cancer. Currently, separate
clinical protocols exist for the administration of retinoids and melatonin as
adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7
human breast tumour cell line, our laboratory has studied the effects of a
sequential treatment regimen of melatonin followed by all-trans retinoic acid
(atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally
responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by
atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a
reduction in the number of cells to below the initial plating density. This
cytocidal effect is in contrast to the growth-suppressive effects seen with
either hormone alone. This regimen of melatonin followed by atRA induced
cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis
(programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax
and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was
reflected morphologically by an increase in the number of lysosomal bodies and
perinuclear chromatin condensation, cytoplasmic blebbing and the presence of
apoptotic bodies. The apoptotic effect of this sequential treatment with
melatonin and atRA appears to be both cell and regimen specific as (a) ER
negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the
simultaneous administration of melatonin and atRA was not associated with
apoptosis in any of the breast cancer cell lines studied. Taken together, the
results suggest that use of an appropriate regimen of melatonin and atRA should
be considered for preclinical and clinical evaluation against ER-positive human
breast cancer.
PMID- 9649125
TI - Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)
retinamide in human breast cancer cell lines.
AB - The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast
epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+)
breast cancer cell lines. We studied and compared the effects of N-(4
hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of
the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231)
breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced
a dose- and time-dependent inhibition of proliferation in both breast cancer cell
lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231
cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous
human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by
1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in
conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines
following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis
showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%,
respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately
20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I
binding and Scatchard analysis revealed a decrease of more than 50% in maximum
binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell
lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately
30% in both tumour cell lines. We conclude that 4-HPR induces a significant down
regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast
cancer cell lines. These findings suggest that, in our model, interference with
the ER signalling pathway is not the only mechanism of breast cancer growth
inhibition by 4-HPR.
PMID- 9649126
TI - Mutations of the Apc gene in experimental colorectal carcinogenesis induced by
azoxymethane in F344 rats.
AB - We investigated in the rat the role of the Apc gene, which is mutated in familial
adenomatous polyposis and sporadic colon cancer in the process leading from
normal colonic mucosa to aberrant crypt foci (ACF) and finally to adenomas and
adenocarcinomas. We analysed mutations in exon 15 of the rat Apc gene using in
vitro synthesized protein assay in 66 ACF and in 28 colon tumours induced by
azoxymethane. No Apc mutations were found in ACF, whereas five mutations were
found in the tumours. The data suggest that mutations of the Apc gene are
associated with the transition from ACF to adenoma and adenocarcinoma and not
from normal mucosa to ACF.
PMID- 9649127
TI - Low-level resistance to camptothecin in a human small-cell lung cancer cell line
without reduction in DNA topoisomerase I or drug-induced cleavable complex
formation.
AB - To study the evolution of camptothecin (CPT) resistance, we have established two
small-cell lung cancer cell lines with low (3.2-fold, NYH/CAM15) and high (18
fold, NYH/CAM50) resistance to CPT by stepwise drug exposure. NYH/CAM50 cells had
reduced topoisomerase I (topo I) content and activity, and consequently CPT
induced DNA single strand breaks (SSBs) were reduced, as measured by alkaline
elution. In contrast, NYH/CAM15 cells had identical topo I content and activity
as compared with wild-type (wt) cells. CPT-mediated SSBs and the rate of their
reversal after drug removal were also equal in wt and NYH/CAM15 cells, as were
doubling time, the fraction of cells in S-phase and DNA synthesis rate in
response to CPT. As the conversion of DNA SSBs to DNA double strand breaks (DSBs)
is thought to represent a critical event leading to cell death, we measured DNA
DSBs by neutral elution. In contrast to DNA SSBs, CPT induced fewer DNA DSBs in
NYH/CAM15 than in wt cells. DNA flow cytometry showed that, in CPT-treated cells,
the G1 phase was emptied as cells accumulated in late S- and G2M phase. A
Spearman rank correlation showed that depletion of G1 and accumulation in late S
and G2M correlated to CPT sensitivity in these three cell lines. In conclusion,
acquired resistance to CPT can occur without a reduction in either topo I enzyme
or CPT-induced cleavable complex formation, while a decrease in the level of CPT
induced DNA DSBs may be of major importance in the early stages of CPT
resistance.
PMID- 9649128
TI - Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell
lung carcinoma cell lines.
AB - We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte
growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung
carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF
stimulated proliferation in only three cell lines and exerted no mitogenic
activity on six lines. The growth of the remaining six lines was inhibited. The
mitogenic effects were not related to the ras genotype of these cell lines, but
the inhibitory effect was more commonly observed in cell lines with relatively
high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced
both scatter activity on monolayer culture and single-cell invasion in collagen
gels in approximately half of these cell lines. Although the ras genotype of
tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines
with the mutant ras genotype more commonly demonstrated a spontaneous motogenic
activity than those with the wild-type ras genotype. When tumour cells were grown
in collagen gels, HGF/SF induced irregular branching extensions of cell
aggregates formed by five out of eight adenocarcinoma cell lines, but significant
lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop
in these tumour cell lines did not influence their spontaneous or HGF/SF-induced
mitogenic, motogenic or morphogenic activities. Overall, our data suggest that
stimulation of cell motility, rather than proliferation or differentiation, is
the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.
PMID- 9649129
TI - Determinants of CPT-11 and SN-38 activities in human lung cancer cells.
AB - Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad
spectrum of anti-tumour activity. Carboxylesterase (CE) catalyses the conversion
of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin), the active form of CPT-11.
The antiproliferative effects of CPT-11 and SN-38, CE-activity and topoisomerase
I protein expression were investigated in five human small-cell lung cancer
(SCLC) cell lines and four human non-small-cell lung cancer (NSCLC) cell lines.
Antiproliferative activity, expressed as IC50 values, was determined using the
MTT assay. CPT-11 was significantly more active in SCLC than in NSCLC cell lines
(P = 0.0036), whereas no significant difference between histological types was
observed with SN-38. A significant correlation (r2 = 0.52, P = 0.028) was
observed between CE activity and chemosensitivity to CPT-11 but not to SN-38, and
significantly higher CE activity was observed in SCLC compared with NSCLC cell
lines (P = 0.025). Western blotting experiments showed topoisomerase I protein
expressions within a factor of 2, and a granular nuclear staining was detectable
in all cell lines by immunocytochemistry of cytospins. No correlation was
observed between protein expression and sensitivity to CPT-11 or SN-38. Cellular
and medium concentrations of CPT-11 and SN-38 were measured by high-performance
liquid chromatography (HPLC) in one SCLC cell line with high CE activity and high
sensitivity to CPT-11, and one NSCLC cell line with low sensitivity to CPT-11 and
CE activity. Intracellular concentrations of CPT-11 and SN-38 were higher in the
SCLC cell line, and this was associated with an increase in cellular uptake of
CPT-11 compared with the medium, and an increased intracellular formation of SN
38. In conclusion, CE activity appears to be associated with higher sensitivity
to CPT-11 in human lung cancer cell lines and may partly explain the difference
in the in vitro sensitivity to CPT-11 between SCLC and NSCLC cells. The
assessment of CE activity in clinical material of lung cancer patients undergoing
treatment with CPT-11 may be warranted. However, other mechanisms may influence
sensitivity to CPT-11, possibly including drug transport.
PMID- 9649130
TI - Telomerase activity in benign and malignant human thyroid tissues.
AB - Telomerase is a specialized ribonucleoprotein polymerase that directs the
synthesis of telomerase repeats at chromosome ends. Accumulating evidence has
indicated that telomerase is stringently repressed in normal human somatic
tissues but reactivated in cancers and immortal cells, suggesting that activation
of telomerase activity plays a role in carcinogenesis and immortalization. In
this work, the status of telomerase activity during the development of human
thyroid cancer was determined using telomeric repeat amplification protocol
(TRAP) in 14 nodular hyperplasia, 14 adenomas, 23 papillary carcinomas and 11
follicular carcinomas. Positive telomerase activity was detected in 2 of 14
nodular hyperplasias (14%), 4 of 14 adenomas (29%), 12 of 23 papillary carcinomas
(52%) and 10 of 11 follicular carcinomas (91%). The cancers that are negative for
telomerase activity are mostly in early stage (stage I or II). These results
suggest that telomerase reactivation plays a role during the development of
thyroid cancer.
PMID- 9649131
TI - Chromosome instability is a predominant trait of fibroblasts from Li-Fraumeni
families.
AB - Previous work has indicated a role for p53 in cell cycle control, genomic
stability and cellular responses to DNA-damaging agents. However, few data are
available for human fibroblasts heterozygous for defined germline mutations in
TP53. We report studies on 25 strains derived from 12 families with Li-Fraumeni
syndrome (LFS) and 18 strains from normal volunteers. The families include three
that are classical LFS families, but in whom no TP53 mutation has been found. In
the families with mutations, increased longevity and resistance to low-dose-rate
ionizing radiation showed a statistically significant association with the
presence of TP53 mutations. However, not all heterozygotes had increased
longevity or were radioresistant, and fibroblasts from cancer-affected members of
LFS families without TP53 mutations showed no significant increase in either of
these end points. In contrast, all mutation-carrying strains showed evidence of
genomic instability, expressed as aneuploidy, and accumulated structural
chromosome aberrations in up to 100% of cells, usually accompanied by loss of the
wild-type TP53 allele, immediately before senescence. Levels of aneuploidy higher
than in normal cells were also observed in fibroblasts from families without TP53
mutations, suggesting that chromosome instability is a major factor in
determining the cancer proneness of these families.
PMID- 9649132
TI - Is chromosome 9 loss a marker of disease recurrence in transitional cell
carcinoma of the urinary bladder?
AB - Investigation of transitional cell carcinoma of the urinary bladder (TCC)
patients classified by recurrence and/or progression has demonstrated that loss
of chromosome 9, as detected by FISH analysis of the pericentromeric classical
satellite marker at 9q12, occurs early. A total of 105 TCCs from 53 patients were
analysed in situ by two independent observers for loss of chromosome 9 using
quantitative fluorescence in situ hybridization (FISH). All 53 primary tumours
were evaluated for chromosomes 9, 7 and 17. Normal ranges for chromosomal copy
number were defined for normal skin epidermis and bladder epithelium. Values for
chromosome 9 copy number outwith the range 1.51-2.10 (mean +/- 3 x s.d. of normal
values) were significantly abnormal. Twenty-five TCCs were detected with
consistent monosomic scores. Of 89 TCCs, in which multiple tumour areas were
analysed, 85 tumours (96%) demonstrated the same chromosome 9 copy number in all
areas (2-6) analysed; only three tumours demonstrated heterogeneity for this
locus. A total of 36% (12 out of 33) of patients with subsequent disease
recurrence demonstrated loss of chromosome 9 in their primary and all subsequent
TCCs analysed. Only a single patient (n = 20) with non-recurrent TCC showed loss
of chromosome 9 (P = 0.0085). Of 53 primary tumours, eight showed significant
elevation of chromosome 17. Of these patients, six demonstrated elevation in
chromosome 7 copy number. No abnormalities were observed in non-recurrent
patients. This study describes rapid quantitation of chromosomal copy number by
FISH using a pericentromeric probe for chromosome 9 in TCC of the urinary
bladder. Routinely fixed and processed material was evaluated without
disaggregation. Strict quality control of FISH demonstrated that this technique
was reproducible in a clinical environment and could be used to detect genetic
changes relevant to patient outcome. It is proposed that loss of chromosome 9
from primary TCC of the urinary bladder identified patients at high risk of
recurrence and possible progression.
PMID- 9649133
TI - BRCA1 mutations in southern England.
AB - If genetic testing for breast and ovarian cancer predisposition is to become
available within a public health care system there needs to be a rational and
cost-effective approach to mutation analysis. We have screened for BRCA1
mutations in 230 women with breast cancer, all from the Wessex region of southern
England, in order to establish the parameters on which to base a cost-effective
regional mutation analysis strategy. Truncating mutations were detected in 10/155
(6.5%) consecutive cases selected only for diagnosis under the age of 40 (nine of
these ten women had a strong family history of breast or ovarian cancer), 3/61
(4.9%) bilateral-breast cancer cases (all three mutations occurring among women
for whom the first cancer was diagnosed under 40 years) and 8/30 (26.6%) breast
cancer cases presenting to the genetics clinic (for whom a strong family history
of breast and/or ovarian cancer was present). Ten different mutations were
detected in 17 families, but three of these accounted for 10/17 (59%) of the
families. The cost of screening the population for mutations in the entire BRCA1
gene is unacceptably high. However, the cost of screening a carefully selected
patient cohort is low, the risk of misinterpretation much less and the potential
clinical benefits clearer.
PMID- 9649134
TI - Increased microvessel density in mucinous compared with malignant serous and
benign tumours of the ovary.
AB - Microvessel density of benign, borderline and malignant ovarian tumours was
studied immunohistochemically using antibodies to the endothelial cell markers
CD31, CD34 and factor VIII-related antigen. Microvessel density was compared in
tumours of different histological subtype, stage and patient outcome. CD31
immunostained sections were examined and regions of high and average microvessel
density were selected. Identical regions were located on CD34- and factor VIII
related antigen-immunostained serial sections and microvessel counts obtained and
converted to vessels mm(-2). CD31 and CD34 immunostaining revealed increased
microvessel density in both the high and average vessel density regions of
mucinous (222.4 +/- 24.8; 79.9 +/- 8.5) compared with serous (105.4 +/- 20.7;
33.3 +/- 6.8) and benign (84.4 +/- 19.4; 20.4 +/- 4.4) tumours (P < 0.001). CD31
and CD34 immunostaining also revealed increased microvessel density in early
stage mucinous tumours (234.6 +/- 28.2; 87.8 +/- 9.2) compared with that observed
in both early- (72.8 +/- 15; 12.9 +/- 2.4) and late- (115.6 +/- 26.5; 29.8 +/-
8.5) stage serous tumours (P < 0.001). No differences in microvessel density in
samples from patients with differing outcomes were observed (P > 0.05). Reduced
factor VIII-related antigen compared with CD31 and CD34 immunostaining was
observed in both borderline and malignant mucinous and serous tumours (P < 0.02)
but not in benign tumours (P > 0.05). Our results contradict the putative
association between increased microvessel density and poor prognosis and suggest
that the level and control of angiogenesis may differ between ovarian tumour
types.
PMID- 9649135
TI - The luminescence immunoassay S-100: a sensitive test to measure circulating S
100B: its prognostic value in malignant melanoma.
AB - In this study we measured S-100B using a recently developed luminometric
immunoassay with a detection limit of 0.02 microg l(-1). By measuring serum S
100B concentrations in 58 apparently healthy individuals a reference value of
0.16 microg l(-1) was found. To assess the sensitivity of the assay we measured
levels of S-100B protein in the serum of 251 patients with cutaneous malignant
melanoma before the start of treatment. Only one of 179 patients with limited
disease had a serum concentration higher than the reference value, whereas
elevated levels were seen in 79% of patients with metastasized disease. In the
latter group the NSE serum concentration was elevated in 42%. Using a receiver
operating characteristic (ROC) curve it is shown that S-100B is a significantly
better parameter than neuron-specific enolase (NSE) for distinguishing patients
with limited disease from those with extensive melanoma. Pretreatment S-100B
values were highly predictive for the period of survival. Patients with limited
disease have increased risk for early death with increasing levels of S-100B
protein. Within the group of patients with positive lymph nodes and/or with
distant metastases, elevated S-100B levels strongly identified high-risk
patients. Our study indicates that the measurement of S-100B as a tumour marker
in the management of patients with cutaneous malignant melanoma has clinical
significance.
PMID- 9649136
TI - Suppression of tumorigenic and metastatic potentials of human melanoma cell lines
by mutated (143 Val-Ala) p53.
AB - Metastatic melanoma, compared with other cancers, appears to be unusual because
of its low frequency of p53 mutations and prevalence of wild-type p53 protein in
advanced malignancy. Here, we examined the effects of wild-type and mutated p53
(143 Val-Ala) on tumorigenic and metastatic potential of two human melanoma cell
lines. The cell line UISO-MEL-4 contains wild-type p53 and is tumorigenic,
whereas UISO-MEL-6 lacks p53 and produces lung and liver metastasis upon s.c.
injection into athymic mice. Our study showed that UISO-MEL-4 stably transfected
with wild-type p53 cDNA driven by cytomegalovirus promoter-enhancer sequences
expressed high levels of p53 and p21 and formed s.c. tumours in vivo. Mutated p53
(143 Val-Ala) expression, on the other hand, inhibited tumour growth in 50% of
cases and produced significantly slower growing non-metastatic tumours. Reduced
tumour growth involved necrotic as well as apoptotic cell death. Inhibition of
tumour growth was abrogated by the addition of Matrigel (15 mg ml(-1)). With UISO
MEL-6 cells, stably transfected with mutant p53, tumour growth was delayed and
metastasis was inhibited. In soft agar colony formation assay, both wild-type and
mutant p53 transfectants reduced anchorage-independent colony formation in vitro.
These data suggest that mutated (143 Val-Ala) p53, which retains DNA binding and
some of the transactivation functions of the wild-type p53 protein, suppresses
tumorigenic and metastatic potentials of human melanoma cell lines in vivo.
PMID- 9649137
TI - Comparative genomic hybridization and telomerase activity analysis identify two
biologically different groups of 4s neuroblastomas.
AB - Chromosomal aberrations of 20 stage 4s neuroblastomas were analysed by
comparative genomic hybridization (CGH). In a subset of 13/20 tumours, telomerase
activity was evaluated by the telomeric repeat amplification protocol (TRAP). The
CGH data were compared with the CGH results of ten stage 1 and 2 (stage 1/2) and
22 stage 3 and 4 (stage 3/4) neuroblastomas. A total of 17/20 stage 4s
neuroblastomas did not progress clinically, whereas tumour progression with
lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing
stage 4s tumours revealed a high rate of whole-chromosome aberrations (73.4%)
with an overrepresentation of mainly chromosomes 2, 6, 7, 12, 13, 17, 18 and an
underrepresentation of mainly chromosomes 3, 4, 11, 14. MYCN amplification or 1p
deletion was observed in only 1/27 or 2/17 clinically non-progressing stage 4s
tumours respectively, whereas all three progressive stage 4s neuroblastomas
showed MYCN amplification, 1p deletion and, in 2/3 cases, distal 17q gains.
Except for one case, telomerase activity was not observed in non-progressing
stage 4s neuroblastomas. In contrast, 4s tumours with lethal outcome revealed
elevated telomerase activity levels. Our data suggest that stage 4s
neuroblastomas belong to two biologically different groups, one of which displays
the genetic features of localized stage 1/2 tumours, whereas the other mimics
advanced stage 3/4 neuroblastomas.
PMID- 9649138
TI - Alterations of TP53 in microdissected transitional cell carcinoma of the human
urinary bladder: high frequency of TP53 accumulation in the absence of detected
mutations is associated with poor prognosis.
AB - We have used microdissection of paraffin-embedded histological sections and
polymerase chain reaction (PCR)-based direct DNA sequencing for 54 transitional
cell carcinoma (TCC) of the bladder, to examine critically the association
between TP53 nuclear accumulation determined by immunohistochemistry and the
presence of TP53 mutations, and to examine their relationship to tumour stage and
grade, as well as patient survival. There was a significant association between
the presence of TP53-positive nuclei (> 10%) and a higher histological stage and
grade (P = 0.0115, P = 0.0151 respectively; Fisher's exact). A significant
association between TP53 gene mutations and TP53 nuclear reactivity in more than
10% of tumour cell nuclei was also observed (P = 0.0003; Fisher's exact).
Mutations were detected in 18/54 (33%) cases together with the wild-type sequence
when analysed from bulk frozen samples, with significant clustering of mutations
in exons 7 and 8. The microdissection method distinguished more clearly between
heterozygous and/or homozygous alterations of the TP53 tumour-suppressor gene,
and clearly showed frequent accumulation of TP53 in the absence of mutations.
When microdissecting immunonegative regions from the same paraffin sections,
three out of ten samples showed the identical mutations detected in the
immunopositive regions. There was a significant association between TP53
immunoreactivity in more than 50% of tumour cell nuclei and decreased survival
among all patients (P = 0.0325; log-rank test). The patients with TP53 mutations
showed a trend for a shorter survival period; however, the association was not
statistically significant at the 95% confidence level (P = 0.132; log-rank test).
In conclusion, our observations show that accumulation of TP53 occurs frequently
in the absence of mutations, and that such accumulation is nevertheless
associated with poor survival when it occurs in a high proportion (> 50%) of
tumour cell nuclei.
PMID- 9649139
TI - Expression of matrix metalloproteinases (MMP-1 and -2) and their inhibitors (TIMP
1, -2 and -3) in oral lichen planus, dysplasia, squamous cell carcinoma and lymph
node metastasis.
AB - Although matrix metalloproteinases (MMPs) are among the potential key mediators
of cancer invasion, their involvement in premalignant lesions and conditions is
not clarified. Therefore, we studied, using in situ hybridization,
immunohistochemistry and zymography the expression and distribution of MMP-1 and
2, and their tissue inhibitors (TIMPs -1, -2 and -3) in oral squamous cell
carcinomas (SCC) and lymph node metastases as well as in oral lichen planus,
epithelial dysplasias and normal buccal mucosa. In oral SCC and lymph node
metastasis, MMP-1 mRNA was detected in fibroblastic cells of tumoral stroma. In
two out of ten carcinomas studied, the peripheral cells of neoplastic islands
were also positive. MMP-2 mRNA expression was noted in fibroblasts surrounding
the carcinoma cells, and no signal in carcinoma cells was detected. A clear TIMP
3 mRNA expression was seen in stromal cells surrounding the neoplastic islands in
all SCCs and lymph node metastases studied. TIMP-1 mRNA was detected in some
stromal cells surrounding the neoplastic islands, whereas the mRNA expression for
TIMP-2 was negligible. On the other hand, expression of MMPs and TIMPs was
consistently low in oral epithelial dysplasias, lichen planus and normal mucosa.
In certain epithelial dysplasias and lichen planus, MMP-1 and -2 mRNA expressions
were detected in few fibroblasts under the basement membrane zone, but normal
mucosa was completely negative. In SCC and lymph node metastasis, a detectable
immunostaining for MMP-1 in stromal cells and in some carcinoma cells was
observed. MMP-2 immunoreactivity was detected in the peripheral cell layer in
neoplastic islands and in some fibroblast-like cells of tumoral stroma.
Immunostaining for TIMP-3 was detected in stromal cells surrounding the
neoplastic islands. A weak positive staining for TIMP-1 was located in tumoral
stroma, whereas the immunostaining for TIMP-2 was negative. Using zymography,
elevated levels of MMP-2 and MMP-9 were observed in carcinoma samples in
comparison with lichen planus or normal oral mucosa. Our results indicate that
the studied MMPs and TIMPs are clearly up-regulated during invasion in oral SCC.
However, there was also a clear, although weak, up-regulation of the expression
of the MMPs but not TIMPs in some of the lichen planus and dysplastic lesions.
PMID- 9649140
TI - Association of tumour necrosis factor alpha and its receptors with thymidine
phosphorylase expression in invasive breast carcinoma.
AB - Angiogenesis is an essential requirement for tumour growth and metastasis and is
regulated by a complex network of factors produced by both stromal cells and
neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha
(TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to
promote tumour angiogenesis. We have demonstrated recently that high numbers of
tumour-associated macrophages (TAMs) are significantly associated with increased
tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We
have also shown that TAMs are a major source of TNF-alpha in invasive breast
carcinomas, and that macrophage-like stromal cells as well as tumour cells
synthesize TP in such tumours. However, little is known of the factors that
regulate the production or activity of these factors in the tumour
microenvironment. As TNF-alpha has been shown to up-regulate TP expression in
tumour cells in vitro we performed an immunohistochemical study to investigate
the possibility that TNF-alpha may be involved in the regulation of TP expression
by malignant breast epithelial cells in vivo. To do this, we used a cocktail of
non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha
expressing macrophages and TNF-alpha bound to its receptors on tumour cells and
endothelial cells in a series of 93 invasive carcinomas of the breast. A
semiquantitative grading system was then used to compare these staining patterns
with that for TP in the same biopsies. TNF-alpha immunoreactivity was also
compared with various important tumour variables known to relate to outcome in
this disease (microvessel density, node status, grade, stage, receptor status and
macrophage infiltration), as well as relapse-free and overall survival data for
these patients. Our data show significant positive correlations between TNF-alpha
bound to its receptors on tumour cells and: (1) TP protein production by tumour
cells, and (2) axillary lymph node status (i.e. metastasis). These results
suggest that tumour cell responsiveness to TNF-alpha produced by neighbouring
TAMs may play a part in the regulation of TP expression by tumour cells as well
as their metastatic behaviour. This may explain, in part, the relationship
between increased macrophage infiltration and angiogenesis in breast cancer, and
further supports the contention that TAMs may represent an important target for
future anti-angiogenic therapies.
PMID- 9649141
TI - Family history and survival in premenopausal breast cancer.
AB - The clinicopathological characteristics of breast cancer in 95 women between the
ages of 24 and 45 years with a family history of breast cancer were compared with
tumours from 329 women with sporadic disease matched for age and year of
diagnosis. There was a trend for the family history patients to have slightly
smaller tumours (mean size 2.49 cm) than the controls (mean 3.04 cm) (Mann
Whitney test, P = 0.09). A significantly greater proportion of the familial cases
had grade III infiltrating ductal carcinoma than did the controls (40% vs 27%;
chi2(1) = 5.64, P = 0.02). Despite this, there were more cases of operable node
negative disease among the study group than among the controls (48% vs 32%;
chi2(1) = 8.2, P = 0.004). There was a highly significant survival advantage for
patients with a family history (chi2 = 22.4, P < 0.001). Five- and 10-year
survival rates were 92% and 87% for those with a family history compared with 70%
and 54% for those in the control group. This survival advantage was maintained
when patients with operable disease only were considered. In multivariate
analysis, which included age, tumour size, stage, histological grade and family
history, family history was an independent predictor of favourable prognosis and,
in a Cox model, was associated with a relative risk of survival of 6.11 (95% CI
2.81-13.28). These results suggest that familial breast cancer has a more
favourable clinical course than the more common sporadic forms of the disease.
PMID- 9649142
TI - Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study
in advanced breast cancer. EORTC Breast Cancer Cooperative Group.
AB - The EORTC Breast Cancer Cooperative Group carried out a randomized trial to
compare doxorubicin with epirubicin as second-line chemotherapy in patients with
metastatic breast cancer. Two hundred and fifty-nine patients with at least one
site of metastatic disease entered this trial, of whom 232 patients were
eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(
2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin
were 36% and 28% respectively (P = 0.173). The median time to progression was 23
weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median
duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P
= 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for
epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and
platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated
group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P =
0.048) were significantly worse in the doxorubicin arm. Nine patients on
doxorubicin and two patients on epirubicin experienced congestive heart failure
(CHF). At the dose levels used in this study, no statistical differences in
response rate and survival were found between the two treatment arms. Treatment
with doxorubicin tended to result in a slightly longer duration of response and
time to progression but doxorubicin was more toxic than epirubicin.
PMID- 9649143
TI - Tamoxifen reduces plasma homocysteine levels in healthy women.
AB - Treatment with tamoxifen is associated with reduced incidence of myocardial
infarction. As plasma homocysteine is an independent risk factor for
cardiovascular disease, we studied the effects of tamoxifen on plasma
homocysteine in 66 healthy women participating in the Italian prevention trial of
breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg
day(-1) or placebo for 5 years. They were aged between 35 and 70 years, had
undergone previous hysterectomy for non-malignant conditions and had no
contraindications to the use of tamoxifen. Plasma levels of total homocysteine
(tHcy) were measured at randomization and after 2 and 6 months. The mean +/- s.d.
plasma levels of tHcy were 7.59 +/- 1.71 micromol l(-1), 7.25 +/- 1.61 and 7.09
+/- 1.33 in the tamoxifen group and 8.07 +/- 2.06, 7.93 +/- 1.77 and 8.12 +/-
2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group
difference over time). The higher the baseline tHcy level, the greater was the
lowering effect of tamoxifen. No statistically significant effect of age, body
mass index or smoking habit on baseline tHcy levels and its variation over time
was found. In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma
tHcy levels in healthy women. This effect may contribute to its protective effect
on myocardial infarction.
PMID- 9649144
TI - Predictive value of topoisomerase IIalpha and other prognostic factors for
epirubicin chemotherapy in advanced breast cancer.
AB - Although cytotoxic chemotherapy is widely used in advanced breast cancer, there
are no powerful predictors for the therapy response. Because topoisomerase
IIalpha (Topo IIalpha) is the molecular target for the anthracycline class of
anti-cancer drugs, we compared the immunocytochemical assay of Topo IIalpha with
other biomarkers in the prediction of clinical response to Topo II inhibitor
chemotherapy. Fifty-five patients with advanced breast cancer were treated with a
single cytotoxic drug, Topo II-inhibitor, epirubicin (30 mg m(-2) weekly up to
1000 mg m(-2)), as first line cytotoxic chemotherapy. Objective response to
treatment was analysed according to UICC criteria. The predictive value of Topo
IIalpha expression, c-erbB2 oncoprotein, p53 tumour-suppressor protein, oestrogen
(ER) and progesterone receptor (PR), S-phase fraction and DNA ploidy were
analysed from representative formalin-fixed paraffin-embedded primary tumour
samples. The proportion of Topo IIalpha-positive cells (Topo IIalpha index)
failed to predict response to epirubicin therapy. Mean Topo IIalpha scores in 29
responding patients were similar when compared with those with no change in
disease progression (n = 13) and those with progressive disease (n = 13) (14.9%
+/- 11.4% vs 15.5% +/- 7.6% vs 17.3% +/- 13.2%, not significant). Among the other
biomarkers tested, overexpression of c-erbB2 oncoprotein and hormone receptor
negativity were significantly associated with poor response. Response rate in
patients with c-erbB2-overexpressing tumours was 32% compared with 65% in
patients with no c-erbB2 overexpression (P = 0.0058). Accordingly, the response
rate for ER-positive patients was 67% compared with 26% in ER-negative patients
(P = 0.0021). Although both negative ER status and c-erbB2 overexpression are
associated with high Topo IIalpha expression in breast cancer, step-wise logistic
regression analysis showed that ER and c-erbB2 were associated with therapy
response independent of Topo IIalpha expression. Histological grade, p53, DNA
ploidy, tumour proliferation rate (S-phase fraction), stage of the disease at
diagnosis, age of the patient, previous anti-oestrogen therapy or site of
metastasis did not predict the response to epirubicin therapy. In conclusion,
despite extensive in vitro evidence, expression of Topo IIalpha is unlikely to
predict the response to Topo II inhibitor chemotherapy in advanced breast cancer.
Among the prognostic biomarkers, overexpression of c-erbB2 oncogene and negative
ER may have predictive value in epirubicin therapy in patients with advanced
breast cancer.
PMID- 9649145
TI - VLA2 integrin expression in breast carcinomas evaluated by automated and
quantitative immunohistochemistry.
AB - VLA2 is thought to be involved in the metastatic process in malignant tumours, in
particular in carcinomatous cell adhesion to vessel basement membrane. VLA2
expression was immunohistochemically investigated in 204 breast carcinomas.
Frozen tissue sections were probed with monoclonal anti-VLA2 using automated
(Ventana ES 320 System) and quantitative (SAMBA 2005 image processor)
immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours
(23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in
tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with
histoprognostic indicators and tumour expression of various antigens detected
using the same method as that for VLA2. The results show that VLA2
immunoexpression was independent of the tumour size, grade, type and aneuploidy,
and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and
P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P <
0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin,
CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and
pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be
elucidated and the clinical relevance of VLA2 immunodetection in breast
carcinomas requires further investigation of the correlation between VLA2
immunocytochemical expression and patients' outcome and response to chemotherapy.
PMID- 9649146
TI - Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL)
and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003
protocol.
AB - From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic
leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell
non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a
short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on
the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to
16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide,
vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high
dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy
(methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15
fractions) was recommended in patients with overt CNS disease. One patient with
Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the
analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and
BM, three; and jaw, one) 4-11 months after diagnosis and two patients never
achieved complete remission (CR). All have died. In seven of the patients who
relapsed, treatment had been modified or delayed because of poor clinical
condition. Seven patients (11%) died of toxicity 11 days to 4 months after
diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n
= 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3
years), 43 patients (69%) survive in CR. This study confirms the effectiveness of
this regimen with regard to the relapse rate (16%), although the rate of toxic
death is of concern.
PMID- 9649147
TI - Pulmonary toxicity after granulocyte colony-stimulating factor-combined
chemotherapy for non-Hodgkin's lymphoma.
AB - Sporadic cases have developed pulmonary toxicity after receiving chemotherapy and
granulocyte colony-stimulating factor (G-CSF). However, because such cases
received chemotherapy that alone frequently causes pulmonary toxicity, the role
of G-CSF in this toxicity has been unclear. CHOP therapy (cyclophosphamide,
doxorubicin, vincristine and prednisolone) only slightly induces pulmonary
toxicity. However, we observed a considerable incidence of this toxicity in non
Hodgkin's lymphoma subjects receiving CHOP therapy and G-CSF (6 out of 52
subjects, 11.5%). In this cohort, among various characteristics, including the
dose and interval of CHOP therapy, only the mean peak leucocyte count (MPLC) with
each therapy cycle was associated with development of this toxicity (MPLC > or =
23.0 x 10(9) l(-1), 6 out of 29 cases; MPLC < 23.0 x 10(9) l(-1), 0 out of 23
cases; P = 0.020). These findings suggest that the effect of G-CSF is the main
determinant of the pulmonary toxicity in these cases. Because the toxicity was
associated with a large MPLC and did not recur in cases readministered G-CSF, an
idiosyncratic reaction to G-CSF is unlikely to be the pathogenesis of this
toxicity. Thus, lowering the G-CSF dose seems to be useful in the prevention of
this toxicity. In all six cases, the time course of manifestation of the toxicity
was the same, and early application of high-dose corticosteroid led to cure. This
knowledge will be helpful in the care of similar cases.
PMID- 9649148
TI - Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for
cure?
AB - B-cell chronic lymphocytic leukaemia (CLL) cannot be cured by conventional
therapy. To improve the prognosis of patients with CLL, we have designed a
sequential treatment strategy that comprises intensive chemotherapy for
mobilization of peripheral blood progenitor cells (PBPCs) and induction of
minimal disease, followed by high-dose radiochemotherapy with stem cell
reinfusion and post-transplant molecular monitoring by polymerase chain reaction
(PCR) amplification of the complementary determining region III (CDRIII) gene. In
a prospective study, we have evaluated this protocol in 18 patients with CLL,
also including early stages of the disease. The median age was 49 (29-61) years;
Binet stages were A, six; B, nine; and C, three. Adverse prognostic factors [high
lymphocyte count and/or diffuse bone marrow (BM) infiltration] were present in 16
out of 18 patients. All patients showed a clone-specific molecular marker as
demonstrated by PCR amplification of CDRIII rearrangements. For stem cell
mobilization and reduction of tumour load, one to two cycles of Dexa-BEAM
chemotherapy were administered, resulting in minimal disease (circulating
lymphoma cells <1 x 10(9) l(-1); BM infiltration <20%; lymphomas <2 cm) in 16 out
of 18 patients, including four patients who already had minimal disease before
Dexa-BEAM. Stem cell harvesting was successful in 14 patients. All grafts [three
BM, 11 peripheral blood (PB)] were purged from leukaemic cells using
immunomagnetic methods. Thirteen patients having achieved minimal disease were
reinfused with purged autologous stem cells (ASC) after preparation with total
body irradiation and cyclophosphamide. Engraftment was delayed in patients
receiving BM (n = 3) but prompt [neutrophils >0.5 x 10(9) l(-1) after 10 (9-13)
days, platelets >20 x 10(9) l(-1) after 11 (9-214) days] in patients restored
with PBPCs (n = 10). Procedure-related deaths did not occur. Although the results
of CDRIII PCR suggest persistence or recurrence of the leukaemic clone in at
least three cases, to date only one patient has relapsed, whereas all others
survive without clinical evidence of disease with a maximum follow-up of 48
months. We conclude that sequential high-dose therapy using Dexa-BEAM and
autologous stem cell transplantation is a safe and highly effective treatment for
patients with CLL. However, a longer follow-up is needed to assess whether
definite cures can be achieved using this strategy.
PMID- 9649149
TI - Combined analysis of differentiation inhibitory factor nm23-H1 and nm23-H2 as
prognostic factors in acute myeloid leukaemia.
AB - Differentiation inhibitory factor (nm23 protein) inhibited the induction of the
differentiation of various leukaemic cell lines. We previously reported that nm23
genes (H1 and H2) were overexpressed in acute myelogenous leukaemia (AML) and
nm23-H1 expression predicted the prognosis of AML, especially AML-M5. To clarify
the correlation between French-American-British (FAB) classification and nm23
expression level and to clarify the involvement of nm23-H2 and nm23-H1 in patient
survival, we investigated the relative levels of nm23-H1 and -H2 mRNA in 76 AML
samples using the reverse transcriptase-polymerase chain reaction. We confirmed
that the expression of both nm23-H1 and -H2 genes in AML samples from three
different hospitals was significantly higher than that in normal blood cells (P <
0.0005). Overexpression of nm23-H1 was observed in each FAB AML-M1, -M2, -M3, -M4
or -M5 subtype, and the predictive effect of nm23-H1 expression on AML prognosis
was shown in FAB AML-M2 and -M5 cases. Although overexpression of nm23-H2 was
also found in each FAB subtype, the expression of nm23-H2 in AML-M1 and -M3 cells
was not significantly higher than that in normal cells. Among AML subtypes, AML
M3 showed the lowest expression levels of both nm23 genes. To understand the
relationship between nm23-H1 and -H2 expression levels, nm23 expression levels
for all the AML cases were plotted and divided into four groups (group A, nm23-H1
and -H2 both high; B, both low; C, only nm23-H1 high; D, only nm23-H2 high). A
statistically significant correlation between the levels of expression of nm23-H1
and -H2 was observed (r= 0.726). Most AML-M3 cases belonged to group B, but not
other types of AML. Analysis of survival probability between the groups showed
that group B survived for significantly longer compared with group A.
Furthermore, AML-M3 cases survived for significantly longer compared with non-M3
cases in the same group B. These data suggest that low expression levels of both
nm23-H1 and -H2 are associated with good prognosis in AML patients.
PMID- 9649150
TI - High-dose cyclosporin with etoposide--toxicity and pharmacokinetic interaction in
children with solid tumours.
AB - The tolerability, anti-tumour activity and pharmacokinetic interaction of high
dose intravenous cyclosporin combined with intravenous etoposide was evaluated in
children. Eighteen patients with recurrent or refractory tumours, all of whom had
previously received etoposide, were treated with a combination of high-dose
cyclosporin and etoposide. In 13, cyclosporin was given as a continuous infusion
(15 mg kg(-1) per 24 h for 60 h) and in five a short 3-hour infusion of 30 mg kg(
1) day(-1) on three consecutive days. Pharmacokinetic profiles of etoposide were
determined with and without cyclosporin. Cyclosporin levels ranged from 1359 to
4835 ng ml(-1) and cyclosporin increased the median area under the concentration
time for etoposide curve from 7.2 to 12.5 mg ml(-1) min. The major toxicity was
acute with varying forms of hypersensitivity reactions. In four cases this was
severe. Hyperbilirubinaemia was present in 25 of 32 courses but was of short
duration. In 14 courses, creatinine and/or urea was elevated, but was also
transient. Significant hypertension was seen in six courses. Four of 17 patients
evaluable for response obtained a partial response and one showed stable disease.
It is concluded that in children given the combination of high-dose cyclosporin
and etoposide, the etoposide dose should be halved in order to achieve an area
under the drug concentration-time curve similar to that with etoposide alone. A
continuous infusion schedule of cyclosporin is better tolerated during the period
of administration but is associated with similar hepatic and renal dysfunction to
a short schedule. The 24% response rate in children who had previously received
etoposide suggests that this may be an effective method of enhancing drug
sensitivity and further phase II evaluation is justified.
PMID- 9649151
TI - Unresectable localized neuroblastoma: improved survival after primary
chemotherapy including carboplatin-etoposide. Neuroblastoma Study Group of the
Societe Francaise d'Oncologie Pediatrique (SFOP).
AB - Neuroblastomas (NBs) were assessed according to INSS recommendations including
MIBG scan and extensive bone marrow staging to eliminate metastatic spread.
Patients with unresectable tumour received primary chemotherapy including two
courses of carboplatin-etoposide (CE) and two of vincristine-cyclophosphamide
doxorubicin (CAdO). Post-operative treatment was to be given only in children
over 1 year of age at diagnosis who had residual disease or lymph node (LN)
involvement. Between 1990 and 1994, 130 consecutive children were registered. In
comparison with resectable primaries, these tumours were more commonly abdominal,
larger and associated with N-myc amplification (NMA). Complete, very good and
partial response (CR, VGPR, PR) to CE were, respectively, 1%, 7% and 44%, overall
response rate (RR) to two courses of CE and two courses of CAdO was 71%, and the
tumour could be removed in all but four of the children. The toxicity was
manageable. The 5-year overall survival (OS) and event-free survival (EFS) were,
respectively, 88% and 78% with a median follow-up of 38 months. In multivariate
analysis, only NMA and LN involvement adversely influenced the outcome,
particularly NMA. Children with unresectable NBs and no NMA fared as well as
children with resectable ones as OS were, respectively, 95% and 99% and EFS 89%
and 91%. Our data show encouraging results in localized but unresectable NBs as
90% of children may be considered as definitely cured, especially those without
NMA.
PMID- 9649152
TI - A study of the feasibility and accuracy of pharmacokinetically guided etoposide
dosing in children.
AB - Pharmacokinetically guided dosing was performed in nine paediatric patients
receiving etoposide. Doses on day 2 of a 2- or 3-day schedule were adapted on the
basis of the day-1 area under the plasma etoposide concentration vs time curve
(AUC). The day-1 AUC was estimated using a limited sampling model and the day-2
target AUC defined by the etoposide dose-AUC relationship observed in 33
children. Target AUC values (4.6-8.2 mg ml(-1) x min) were achieved with a high
degree of precision and with little bias (mean error 11% and root mean squared
error 15% respectively). Pharmacokinetic parameters were similar to those
reported previously in children, although interpatient pharmacokinetic
variability was less than that observed previously: plasma clearance, 23 (18-26)
ml min(-1) m(-2); volume of distribution at steady state (Vdss), 6.0 (3.9-8.9) l
m(-2); t(1/2) 254 (127-550) min (median and range). This study has demonstrated
that pharmacokinetically guided dosing with etoposide is feasible. However,
pharmacokinetically guided dosing is likely to be of most benefit in patients
with abnormalities of renal or hepatic function, or in children with prior
exposure to cisplatin.
PMID- 9649153
TI - Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for
the treatment of central nervous system malignancies.
AB - We have previously demonstrated a 33% response rate in patients with primitive
neurectodermal tumours after the direct injection of 131I-monoclonal antibodies
(MAbs) into the cerebrospinal fluid (CSF). Dose-limiting toxicity is
myelosuppression due to the passage of the radioimmunoconjugate from the CSF to
the blood compartment. This occurs at doses of 2220 MBq of 131I-MAb and above,
although this is not seen in all patients studied and appears to be related to
the degree of prior therapy received. Rather than attempting to improve the
efficacy of this approach to the treatment of disseminated disease within the CSF
compartment by dose escalation and haemopoietic rescue, we have explored the
possibility of repeatedly administering the radioimmunoconjugate. Eight patients
were recruited to the study, two of whom received two and six of whom received
three injections of 131I-MAb. After repeated administration of 131I-MAb
pharmacokinetic data revealed that, with one exception, the radioimmunoconjugate
cleared from the CSF compartment with similar kinetics, while its residence time
in the blood decreased with each injection. This was due to the development of an
anti-mouse Ig response in the blood. Clearance of 131I-MAb from the ventricular
CSF appears to be independent of the presence of an anti-mouse Ig response in
this compartment. The differential clearance of the radioimmunoconjugate from the
ventricular CSF and from the blood results in a marked increase in the
therapeutic index that can be achieved. Up to 5920 MBq of 131I-MAb was
administered as the third injection of radioimmunoconjugate and combined doses of
up to 12,500 MBq were given without either haematological or neurological
toxicity. These data illustrate that dose escalation and thus an increase in the
dose rate delivered to tumour cells within the CSF is possible if ways are found
to reduce the residence time of the radioimmunoconjugate in the blood
compartment. Suggestions as to how this can best be achieved are reviewed in
detail.
PMID- 9649154
TI - Demonstration of increased collagen synthesis in irradiated human skin in vivo.
AB - Fibrosis is a common side-effect of radiation therapy. As a complex network of
cytokines and other mediators plays a central role in the process leading to
fibrosis, we used an in vivo method to measure skin collagen synthesis, taking
into account the physiological conditions. We determined suction blister (i.e.
interstitial) fluid concentrations of types I and III procollagen propeptides,
reflecting types I and III collagen synthesis, in irradiated and unirradiated
skin of breast cancer patients 1-5 years after surgery and radiation therapy,
hence using the patients as their own controls. The mean concentrations of the
measured collagen markers were approximately two times higher in the irradiated
skin than in the unirradiated contralateral breast skin. The difference slowly
diminishes with time. These results indicate that abundant collagen synthesis in
the irradiated skin continues several years after discontinuation of the
radiation therapy, leading to fibrosis. The method outlined here offers a new in
vivo perspective to study events leading to radiation fibrosis.
PMID- 9649155
TI - Effective treatment of cutaneous and subcutaneous malignant tumours by
electrochemotherapy.
AB - Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents
by administering the drug in combination with short intense electric pulses. ECT
is effective because electric pulses permeabilize tumour cell membranes and allow
non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study
was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on
cutaneous and subcutaneous tumours. This article summarizes results obtained in
independent clinical trials performed by five cancer centres. A total of 291
cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant
melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma
(87) were treated in 50 patients. Short and intense electric pulses were applied
to tumours percutaneously after intravenous or intratumour administration of
bleomycin. The tumours were measured and the response to the treatment evaluated
30 days after the treatment. Objective responses were obtained in 233 (85.3%) of
the 273 evaluable tumours that were treated with ECT. Clinical complete responses
were achieved in 154 (56.4%) tumours, and partial responses were observed in 79
(28.9%) tumours. The application of electric pulses to the patients was safe and
well tolerated. An instantaneous contraction of the underlying muscles was
noticed. Minimal adverse side-effects were observed. ECT was shown to be an
effective local treatment. ECT was effective regardless of the histological type
of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous
and subcutaneous tumours in patients with minimal adverse side-effects and with a
high response rate.
PMID- 9649156
TI - Aberrant crypt foci in patients with colorectal cancer.
AB - Aberrant crypt foci (ACF) are clusters of abnormally large colonic crypts
identified on the mucosal surface of the human colon. They are thought to be
preneoplastic lesions. The aim of the present study was to compare density
(number of ACF per square cm of mucosal surface), crypt multiplicity (number of
crypts per ACF) and histology of ACF in colonic resections of colorectal cancer
patients resident in two Italian provinces with a twofold difference in
colorectal cancer incidence rates. Thirty-two and 26 colonic resections were
collected after operation in Ragusa (Southern Italy) and Modena (Northern Italy),
respectively, and fixed in 10% formalin. Mucosal layers were observed under a
light microscope at 25x after staining with methylene blue. Density of ACF was
significantly higher in Modena (median 0.101 ACF cm(-2)) than in Ragusa (0.049, P
= 0.001), whereas there was no difference in crypt multiplicity. ACF were
classified into three groups according to histological features: ACF with mild
alterations (hypertrophic ACF, 73%), ACF with hyperplasia (hyperplastic ACF, 17%)
and ACF with dysplasia (microadenomas, 10%). The proportions of ACF in the three
groups were similar in the two provinces. Density of ACF was higher and crypt
multiplicity lower proceeding from proximal to distal large bowel. Microadenomas
were observed only in the colon, whereas hyperplastic ACF were more frequent in
the rectum. In conclusion, density of ACF correlates with colorectal cancer rates
in two Italian provinces, and shows a positive gradient from proximal to distal
large bowel. Histology of ACF suggests that they may be precursors of both
hyperplastic and adenomatous polyps. These data provide further evidence of the
role of ACF in human colorectal carcinogenesis.
PMID- 9649157
TI - Moderate amplifications of the c-myc gene correlate with molecular and
clinicopathological parameters in colorectal cancer.
AB - C-myc gene activation is a common event in multiple types of neoplasia and has
been associated with different cellular processes relevant to the malignant
transformation of cancer cells. C-myc gene amplification has been analysed in
colorectal carcinomas by means of an innovative DNA fingerprinting method based
on the arbitrarily primed PCR. This method requires a low amount of DNA, uses
multiple internal controls and appears sensitive and reproducible.
Clinicopathological and molecular correlates have been investigated in a series
of 70 colorectal carcinomas. The incidence of c-myc amplification was 26%,
ranging from two- to fivefold increase in copy number. C-myc amplification
occurrence was more frequent in more advanced stages of tumour invasion (P <
0.001) and was associated with mutations in the p53 tumour-suppressor gene (P =
0.048). The presence of c-myc amplification was indicative of a shorter disease
free survival period but, because of its strong association with Dukes' stage,
its prognostic value is questionable.
PMID- 9649158
TI - Plasma levels of tumour necrosis factor and its soluble receptors correlate with
clinical features and outcome of Hodgkin's disease patients.
AB - A prospective study was performed to assess the use of plasma measurement of
tumour necrosis factor (TNF), lymphotoxin alpha (LT alpha) and their soluble
receptors (p55 and p75) for prognostic risk assignment in 61 patients with
Hodgkin's disease. Plasma levels of TNF, p55 and p75, but not of LT alpha, were
higher in Hodgkin's disease patients than in healthy controls. Plasma levels of
TNF, p55 and p75 were associated with several prognostic factors for Hodgkin's
disease, including those related to the host (age, performance status) and to the
tumour (disease stage, extranodal site involvement, bulky tumour, serum levels of
LDH and beta2-microglobulin, histology). Elevated plasma levels of TNF, p55 and
p75 were also associated with several parameters reflecting an immune activation,
including the presence of B symptoms, elevated serum levels of gammaglobulins,
alkaline phosphatase and fibrinogen, as well as peripheral monocytosis, anaemia
and low serum albumin levels. Finally, elevated TNF ligand receptor plasma
markers were associated with a lower incidence of complete response to therapy
and predicted shorter free-from-progression survival and overall survival of the
patients. These results indicate that the plasma levels of TNF and its soluble
receptors correlate with clinical features and outcome of patients with Hodgkin's
disease.
PMID- 9649159
TI - A phase I/II study of multicyclic dose-intensive chemotherapy supported with G
CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two
consecutive cohorts of patients.
AB - We investigated the reconstitutive potential of haematopoietic progenitor cells
collected in autologous whole blood during multicycle dose-intensified
chemotherapy. Forty patients with metastatic solid tumours were treated with up
to six cycles of cisplatin and escalating doses of ifosfamide every 14 days.
Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide
over 24 h and mesna over 36 h. The first cohort of patients received granulocyte
colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was
reached in cohort 1, the study continued with a second cohort of patients, in
whom, in addition to G-CSF on days 4-14, 500 ml of G-CSF and chemotherapy
'primed' whole blood was collected on day 15, i.e. on day 1 of treatment cycles
two to six, before cisplatin administration. This volume of blood was kept
unprocessed at 4 degrees C and reinfused 20-24 h after the completion of
ifosfamide. In cohort 1, dose-limiting toxicity (DLT) was reached at ifosfamide
6.0 g m(-2) with two out of six of the patients developing neutropenic fever.
Although in cohort 2 no neutropenic fever was encountered, neither the frequency
nor the duration of grade 4 neutropenia and thrombocytopenia were reduced.
Cumulative asthenia resulted in DLT at 7.0 g m(-2). The median number of CD34+
cells in 500 ml of whole blood after the first cycle (i.e. at start of cycle 2)
was 1.15 x 10(6) kg(-1). This number was significantly greater after the second
cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually decreased after cycles
three to six. After storing whole blood, the number of CD34+ cells had not
decreased (median + 10%). We conclude that the method of combined bone marrow
support by G-CSF and haematopoietic progenitor cells in autologous whole blood
collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does
not result in clinically measurable reduced bone marrow toxicity compared with
what can be expected by the use of G-CSF alone.
PMID- 9649160
TI - Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs
carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung
cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task
Force (FONICAP).
AB - In the present multicentre randomized phase II trial, the activity and toxicity
of three platinum-based combination regimens for the treatment of advanced non
small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP
(mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and
cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1,
ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days)
and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8
every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49
patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent
of the patients had stage IV disease. Response rates, calculated on an 'intention
to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95%
CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were
256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively.
Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was
observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN
respectively. This multicentre phase II randomized trial shows that MVP, PIN and
CaN can be administered on an outpatient basis with acceptable toxicities.
Unfortunately, the three regimens showed an activity significantly lower than
that reported in previous single-institution phase II trials.
PMID- 9649161
TI - The in vitro radiosensitivity of human head and neck cancers.
AB - A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical
specimens of malignant head and neck tumours of different histologies. Using a
soft-agar clonogenic assay, the material was assessed for the ability to grow in
culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity
(surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74%
(104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2
was obtained for 88 of 140 specimens, representing a success rate of 63% with a
mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no
significant differences in radiosensitivity between different sites of the head
and neck region. There were no significant relationships between SF2 and disease
stage, nodal status, tumour grade, patient age, primary tumour growth pattern and
CFE. The results were compared with those for other tumour types previously
analysed with the same assay. The distribution of the SF2 values for the head and
neck tumours was similar to that for 145 cervix carcinomas and there was no
significant difference in mean radiosensitivity between the two tumour types.
Also, there was no significant difference in radiosensitivity between head and
neck tumours and either breast or colorectal cancers. However, a group of eight
lymphomas was significantly more radiosensitive. These results confirm the
feasibility of carrying out radiosensitivity measurements using a soft-agar
clonogenic assay on head and neck tumours. In addition, the work has shown that
radiosensitivity is independent of many clinical parameters and that the mean
value is similar to that reported for cervix carcinomas.
PMID- 9649162
TI - A multicentre phase II study of carboplatin and prolonged oral etoposide in the
treatment of cancer of unknown primary site (CUPS).
AB - Cisplatin-based combination chemotherapy is frequently used to treat patients
with carcinoma of unknown primary site (CUPS). Response rates in the literature
range from 12% to 26% and median survival from 5 to 7 months. The goal of this
study was to evaluate the combination of carboplatin and prolonged oral etoposide
in patients with CUPS, with the hope of minimizing toxicity but improving
efficacy and convenience. Treatment consisted of carboplatin, 300 mg m(-2) on day
1, and oral etoposide 50 mg on days 1-20, every 4 weeks for up to nine cycles. A
total of 33 patients were treated and all were evaluable for toxicity. Non
haematological toxicity was mild to moderate, with the exception of one case of
grade 4 stomatitis. Grade 4 leucopenia was observed in eight (24%) patients and
sepsis in four (12%), with two and possibly three treatment-related deaths. For
the 26 patients evaluable for response, the response rate was 23% with responses
lasting a median of 11 months (range 7-13 months), with one patient still
responding at 12 months. An additional nine patients (35%) had stable disease.
Median survival for all patients was 5.6 months (range 2 weeks to 33 months). The
combination of carboplatin with prolonged oral etoposide has moderate activity
similar to that of other platinum-based regimens and is a well tolerated,
convenient, outpatient regimen. Dosing according to estimated creatinine
clearance to achieve a carboplatin AUC of 6.0 mg ml(-1) min might have decreased
the incidence of severe myelotoxicity without compromising the regimen's
efficacy.
PMID- 9649163
TI - Predictors of patients' mental adjustment to cancer: patient characteristics and
social support.
AB - Because being diagnosed with cancer is considered to be extremely stressful,
cancer patients' mental adjustment has been widely studied. Previous studies have
revealed that cancer patients' mental adjustment is correlated with the quality
of life and the degree of psychological distress and have suggested that one of
the most adaptive adjustments is 'fighting spirit' whereas one of the most
maladaptive is 'helplessness/hopelessness'. However, little is known about the
association between patients' mental adjustment to cancer and their spouses
characteristics or social support network. This paper describes a study of cancer
patients' characteristics and social support factors as predictors of the
patients' responses to having cancer. A total of 455 ambulatory cancer patients
completed the Mental Adjustment to Cancer (MAC) scale and participated in a
structured interview about their characteristics and social support. The results
of multiple regression analysis suggested that size of household, performance
status, support from physicians and satisfaction with support were predictive of
patients' fighting spirit, whereas age, education, size of household, performance
status and satisfaction with support were predictive of
helplessness/hopelessness.
PMID- 9649164
TI - Prostate-specific antigen in the cerebrospinal fluid leads to diagnosis of
solitary cauda equina metastasis: a unique case report and review of the
literature.
AB - A 79-year-old male patient presented with a subacute cauda syndrome caused by an
intradural metastasis of the lumbosacral caudate fibres from an adenocarcinoma of
the prostate, which had been treated 5 years earlier with external beam radiation
therapy. Diagnosis could not be established by repeated magnetic resonance images
(MRIs) during a 2-year period of increasingly severe radicular pain. Eventually,
a small tumour mass could be visualized on the fourth MRI. Repeated normal serum
prostate-specific antigen (PSA) did not hint at a prostate cancer metastasis
(range 2.4-5.1 ng ml(-1)); however, PSA in the cerebrospinal fluid was found to
be elevated (29.1 ng ml(-1)). Empirical radiation therapy of the caudate region
did not improve radicular pain. Therefore, an exploratory surgical procedure was
conducted, which confirmed the suspicion of an intradural prostate cancer
metastasis. In conclusion, PSA in the cerebrospinal fluid provides a useful
diagnostic tool for detecting intradural prostate cancer metastasis.
PMID- 9649165
TI - The halcyon days of clinical field studies of dental caries prevention, 1960
1980.
PMID- 9649166
TI - Localization of estrogen-receptor-related antigen in human odontoblasts.
AB - Estrogen receptors have been demonstrated in many osteogenic cell lines.
Recently, we showed that estrogen deficiency induced by ovariectomy caused
enhanced dentin formation in adult rats, suggesting that estrogen receptors may
be present in dental tissues. Nothing is known about estrogen receptors in human
teeth. We used immunohistochemical staining and immuno-blotting to demonstrate
the presence of estrogen receptors in human pulp and/or the pulpo-dentinal
border. Unerupted human wisdom teeth were surgically removed, frozen in liquid
nitrogen, and prepared for immunological studies. Western blot analysis with
monoclonal antibodies specific for human estrogen-receptor-related antigens
demonstrated an approximately 29-kDa clear double band in the material scraped
from the predentin-odontoblast border and in the fluid that emerged into the
pulpal chamber, evidently from the odontoblasts. A weaker double band was also
present in pulpal tissue samples. By immunohistochemical staining, estrogen
receptor-related antigens were visualized in the predentinal-odontoblast region
and in the pulpal blood vessels. Our results suggest the presence of estrogen
receptors in human teeth, and thus the previously reported enhancement of the
dentin formation in rats after ovariectomy may be mediated via these receptors.
PMID- 9649167
TI - Quantitative analysis of amelogenin solubility.
AB - Amelogenins are a group of extracellular enamel matrix proteins which are
believed to be involved in the regulation of the size and habits of forming
enamel crystals. The aim of this study was to compare the solubility properties
of several amelogenins at various pH (from 4.0 to 9.0) at constant ionic strength
(IS), and to examine the influence of buffer composition, IS, and divalent metal
ions (including Ca2+, Mg2+, and Zn2+) on amelogenin solubility. The solubility of
the recombinant murine amelogenin ("rM179") was minimum near its isoelectric
point and increased rapidly below and above, regardless of buffer composition. A
similar trend was observed for the native porcine ("25K") amelogenin. Porcine
"23K" amelogenin was only sparingly soluble from pH of 4.0 to 9.0, in contrast to
the analogous recombinant "rM166", which was more soluble in acidic solutions.
The synthetic amelogenin polypeptide "TRAP" was extremely insoluble, while
synthetic LRAP was readily soluble. Porcine "20K" amelogenin solubility increased
strikingly as the solution pH was lowered from 7.0 to 6.0. Increasing IS
decreased the solubility of rM179. While Zn2+ reduced rM179 solubility, Ca2+ and
Mg2+ showed no significant effects. We conclude that the solubility of amelogenin
was dependent on the primary structure, solution pH, and IS, and the low
solubility of amelogenins under physiological conditions may result from their
tendency to form quaternary (aggregate) structures in vivo.
PMID- 9649168
TI - CO2 laser inhibitor of artificial caries-like lesion progression in dental
enamel.
AB - Several studies during the last 30 years have demonstrated the potential of laser
pre-treatment of enamel or tooth roots to inhibit subsequent acid-induced
dissolution or artificial caries-like challenge in the laboratory. The overall
objective of ongoing studies in our laboratories is to determine, systematically,
the optimum sets of parameters for carbon dioxide laser irradiation that will
potentially effectively inhibit dental caries in enamel and tooth roots. The aim
of the present study was to examine the roles of wavelength and fluence in the
prevention of caries progression in vitro in enamel by means of a pH-cycling
model. The hypothesis to be tested was that the highly absorbed 9.3- and 9.6
microm wavelengths would be efficiently converted to heat, creating a temperature
sufficiently high to reduce the acid-reactivity of the mineral and inhibit caries
like lesion progression in dental enamel. One hundred and sixty caries-free tooth
crowns were cleaned and varnished with acid-resistant varnish, leaving one
exposed window of enamel. Twelve groups of 10 enamel samples were irradiated in
their individual windows by one of the four wavelengths (9.3, 9.6, 10.3, or 10.6
microm) of a tunable CO2 laser. Energy per pulse was 25, 50, 100, 200, or 250 mJ
(25 pulses). Repetition rate was 10 Hz, and beam diameter was 1.6 mm. Fluence
conditions of 1 to 12.5 J/cm2 per pulse were produced. All teeth, including 40
non-irradiated controls, were subjected to pH-cycling to produce artificial
caries-like lesions. Results were assessed by cross-sectional microhardness
testing. Inhibition of caries progression of from 40% to 85% was achieved over
the range of laser conditions tested. At 9.3 and 9.6 microm, 25 pulses at
absorbed fluences of 1 to 3 J/cm2 produced inhibition on the order of 70% with
minimal subsurface temperature elevation (< 1 degree C at 2 mm depth), comparable
with inhibition produced in this model with daily fluoride dentifrice treatments.
Safety and efficacy studies will be required in animals and humans before these
promising laboratory results can be applied in clinical practice.
PMID- 9649169
TI - Comparison between Er:YAG laser and conventional technique for root caries
treatment in vitro.
AB - Effective ablation of dental hard tissues by means of the erbium-doped:yttrium
aluminum garnet (Er:YAG) laser has been reported recently, and its application to
caries removal and cavity preparation has been expected. However, few studies
have investigated the capability of the Er:YAG laser to treat caries. In the
present study, the effectiveness of caries removal by using an Er:YAG laser in
vitro was compared with that of conventional mechanical treatment. Thirty-one
extracted human teeth with root caries were used. Half of the caries in each
tooth was treated with the Er:YAG laser, and the other was removed with a
conventional bur or was left untreated as a control. Laser treatment was
performed by means of a combination of contact and non-contact irradiation modes
with cooling water spray, with a new fiber delivery and contact probe system.
Conventional bur treatment was conducted by means of a low-speed micromotor.
Measurements of the time required for caries removal, histopathological
observations of decalcified serial sections, scanning electron microscope (SEM)
observations, and hardness measurements of the treated cavity-floor dentin were
performed for each treatment. Due to the careful irradiation technique, a longer
treatment time was required for the complete removal of carious dentin by the
Er:YAG laser. However, the Er:YAG laser ablated carious dentin effectively with
minimal thermal damage to the surrounding intact dentin, and removed infected and
softened carious dentin to the same degree as the bur treatment. In addition, a
lower degree of vibration was noted with the Er:YAG laser treatment. The SEM
examination revealed characteristic micro-irregularities of the lased dentin
surface. Our results show that the Er:YAG laser system is promising as a new
technical modality for caries treatment.
PMID- 9649170
TI - Activation of the immune system and systemic immune-complex deposits in Brown
Norway rats with dental amalgam restorations.
AB - Dental amalgam restorations are a significant source of mercury exposure in the
human population, but their potential to cause systemic health effects is highly
disputed. We examined effects on the immune system by giving genetically mercury
susceptible Brown Norway (BN) rats and mercury-resistant Lewis (LE) rats silver
amalgam restorations in 4 molars of the upper jaw, causing a body burden similar
to that described in human amalgam-bearers (from 250 to 375 mg amalgam/kg body
weight). BN rats with amalgam restorations, compared with control rats given
composite resinous restorations, developed a rapid activation of the immune
system, with a maximum 12-fold increase of the plasma IgE concentration after 3
wks (p < 0.001; Mann-Whitney's test). LE rats receiving amalgam restorations
showed no significant increase of plasma IgE (p > 0.05). After 12 wks, BN rats
with amalgam restorations showed significantly increased (p < 0.05) titers of
immune-complex (IC) deposits in the renal glomeruli and in the vessel walls of
internal organs. These rats also showed a significant (p < 0.05), from six- to
130-fold, increase in tissue mercury concentration in the concentration order
kidney > spleen > cerebrum occipital lobe > cerebellum > liver > thymus, and the
tissue silver concentration was significantly (p < 0.05) increased from three- to
11-fold. Amalgam-implanted BN rats showed a significant (p < 0.05) increase in
copper concentration in the kidney and spleen, and in kidney selenium
concentration. We conclude that dental amalgam restorations release substantial
amounts of their elements, which accumulate in the organs and which, in
genetically susceptible rats, give rise to activation of the immune system and
systemic IC deposits.
PMID- 9649171
TI - The process of physical weakening and dissolution of the HA-coated implant in
bone and soft tissue.
AB - Hydroxyapatite (HA)-coated implants were developed to promote osseointegration of
titanium implants and to overcome the mechanical drawbacks of solid HA implants.
Although many clinical reports on the prognosis of HA-coated implants have
reported high success rates, the risks of dissolution and weakening of the
coating have been noted. We hypothesized that the chemical and mechanical
stability of HA coating are affected by its microstructural characteristics. The
present study investigates differences in the microstructures of available HA
coated implants, before and after implantation into the coxal bones of dogs for
periods ranging from 3 weeks to 10 months and under the coxal periosteum of dogs
for 10 months. The results of transmission electron microscopy and energy
dispersive x-ray analysis revealed that crystallization of super-fine HA crystals
occurred in the amorphous phase of the HA coating and progressed over time. This
crystallization weakens HA-coated implants by making the amorphous phase brittle,
causing stress accumulation within the coating, and causing a decrease in the
binding strength between the coating and the substrate. Furthermore, the HA
coating dissolved in soft tissue. Dissolution started with the super-fine HA
crystals in the crystallized portion that was originally part of the amorphous
phase.
PMID- 9649172
TI - Do dental composites always shrink toward the light?
AB - Many of the current light-curing composite restorative techniques are
rationalized in compliance with the theory that composite shrinks toward the
light. Shrinkage directed toward the margins is believed to be responsible for
the observed improved marginal properties. However, the dental literature does
not consistently support this theory. Experimental determination of contraction
patterns is very difficult. In this study, a finite element technique is used to
analyze the direction of composite shrinkage as it cures. The process of
polymerization can be characterized by pre- and post-gel phases. The stress
developed in a restoration can be relieved quickly by the flow of material still
in the pre-gel phase. Residual stresses arise after gelation. Both auto- as well
as photo-curing composites were analyzed. In photo-curing composites, the gel
point varies throughout the material with the intensity of the light.
Experimentally determined light transmittance data for different materials were
used in the simulation. Degree of cure and time-dependent shrinkage properties
were also included from experimental measurements. The analysis showed that the
shrinkage direction was not significantly affected by the orientation of the
incoming curing light, but instead was mostly determined by the bonding of the
restoration to the tooth and by the free surfaces. Consequently, differences
between the contraction patterns of auto- and photo-cure were minimal. It was
concluded that composite does not shrink toward the light, but that the direction
is predominantly determined by cavity shape and bond quality. Improved marginal
properties should be pursued by the optimization of other factors, such as the
polymerization process, the curing procedure, and the bond quality. The direction
of shrinkage vectors in response to light position does not seem to be an
appropriate criterion for the optimization of marginal quality.
PMID- 9649173
TI - Distortion behavior of heat-activated acrylic denture-base resin in conventional
and long, low-temperature processing methods.
AB - There have been many reports on fatal distortion of heat-activated acrylic
denture-base resin which is still widely used in the field of removable
prosthodontics. However, these reports have failed to report quantitatively on
polymerization and thermal shrinkage factors. In the present study, we attempted
to verify that the shrinkage of heat-activated acrylic denture-base resin was
caused mainly by thermal contraction after processing. Furthermore, we examined
the degree of distortion resulting from long, low-temperature processing, and
compared the results with that of the conventional method. The strain gauge and
thermo-couple were embedded in a specimen at the time of resin packing. The
measurement started from the beginning of processing and continued until the
specimen was bench-cooled and immediately before and after it was de-flasked, as
well as during seven-day immersion in water at 37 degrees C. The resin expanded
when processed by the conventional method. Meanwhile, mild shrinkage, possibly
polymerization shrinkage, was observed when the resin was processed by the low
temperature method. This suggested that polymerization shrinkage was compensated
for by thermal expansion during processing by the conventional method. Moreover,
the shrinkage strains in the period from the completion of processing to
immediately after de-flasking, in both the conventional and low-temperature
methods, were identical to the theoretical value of thermal shrinkage which we
obtained by multiplying the linear coefficients of thermal expansion by
temperature differences. The shrinkage strain in the specimen processed by the
low-temperature method, measured from the end of processing to immediately after
de-flasking, averaged 64% of that in the specimen processed by the conventional
method. The results revealed quantitatively that the shrinkage of heat-activated
acrylic denture-base resin was mainly thermal shrinkage, and demonstrated the
advantage of the low-temperature method in reducing thermal shrinkage.
PMID- 9649174
TI - Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non
functional masticatory activity in the rat, assessed by incisal attrition.
AB - Observational methods and the recording of nonspecific jaw movements or
masticatory muscle activity have been used to evaluate oral parafunctional
movements in animal models of bruxism. In this study, we have used a new approach
in which the non-functional masticatory activity in the rat was assessed by the
measurement of incisal attrition, with the aim of investigating the role of
diverse factors involved in the etiology of bruxism. We quantified the attrition
rate weekly by making superficial notches in the lower incisors and measuring the
distances to the incisor edges. Repeated stimulation of the dopaminergic system
with apomorphine led to an enhancement of the non-functional masticatory activity
(p < 0.0001). The severity of the apomorphine-induced oral behavior was
positively correlated (r(s) = 0.69, p < 0.01) with an increase in the incisal
attrition rate (20.9%, p < 0.0001). Apomorphine-induced non-functional
masticatory activity was strongly enhanced by the placement of an acrylic cap on
both lower incisors (306%, p < 0.0001), but not by the cutting of a lower
incisor. Repeated cocaine administration also increased the attrition rate
(22.5%, p < 0.0001). However, neither chronic blockade of dopaminergic receptors
with haloperidol, nor its withdrawal, modified attrition. In addition, since
emotional disturbances are considered to be causal factors of bruxism, we tested
whether experimental stress might accelerate tooth wear. Exposure to two
different chronic stress regimes did not induce significant changes in incisal
attrition. Moreover, exposure to chronic stress after the withdrawal of chronic
haloperidol treatment did not alter attrition either. These results partially
support the role of the central dopaminergic system in bruxism and suggest that
stress, in general, may not be a relevant factor in tooth wear.
PMID- 9649175
TI - Pain maps from facial pain patients indicate a broad pain geography.
AB - Two hundred consecutive female patients, who were referred to a university-based
facial pain clinic, were asked to mark all painful sites on sketches showing the
contours of a human body in the frontal and rear views. The drawings were
analyzed with transparent templates containing 1875 (frontal view) and 1929 (rear
view) square cells of equal size. The average patient scored 71.8 cells in the
frontal and 99.7 cells in the rear view (corresponding to 3.8% and 5.2% of the
maximum possible scores). In individual patient drawings, however, up to 42.7%
and 44.9% of all cells were marked. Only 37 cases (18.5%) exhibited pain that was
limited to the trigeminal system. An analysis of the pain distribution according
to the arrangements of dermatomes revealed three distinct clusters of patients:
(1) pain restricted to the region innervated by the trigeminal nerves (n = 37);
(2) pain in the trigeminal dermatomes and any combination involving the spinal
dermatomes C2, C3, and C4, but no other dermatomes (n = 32); and (3) pain sites
involving dermatomes in addition to the ones listed above (n = 131). Mean ages in
the three clusters were 38.7, 35.5, and 37.5 years, respectively (p = 0.62,
n.s.). Widespread pain existed for longer durations (median, 48 months) than
conditions involving local and regional pain (median, 24 months) (p = 0.02, s.).
Our findings showed that among a great percentage of persistent facial pain
patients the pain distribution is more widespread than commonly assumed, and that
the persistence of pain in the regional and widespread pain presentations is
significantly greater than in cases with pain limited to the trigeminal system.
PMID- 9649176
TI - Prostatein (or rat prostatic steroid binding protein) is a major autoantigen in
experimental autoimmune prostatitis.
AB - Experimental autoimmune prostatitis (EAP) is a disease that could be considered
an experimental model of human non-bacterial prostatitis. In this experimental
model, male rats are intradermally immunized with a saline extract of male sex
accessory glands (RAG) in an adequate adjuvant. The prostatitis observed in the
immunized animals develops as a consequence of the immune response against RAG
antigens, and the histological lesion is strikingly similar to the pattern of
prostatic inflammation observed in the human disease. In this study, we purified
one of the prostatic autoantigens recognized by the autoantibodies in our model.
Amino acid sequence analysis identified the purified protein as prostatein or rat
prostatic steroid binding protein, a member of the uteroglobin superfamily.
Prostatein was recognized not only by the humoral autoimmune response, but also
by the cellular autoimmune response. Certainly, the DTH response and lymph node
cell proliferative assays against prostatein in immunized animals yielded
positive results. Prostatein is not only the target of the autoimmune response in
animals immunized with the whole extract, but also an inducing antigen of the
disease. Purified prostatein, when incorporated to an adequate adjuvant, elicited
cellular and humoral autoimmune response and lesion in the prostate gland. The
identification of one of the target antigens in autoimmune prostatitis has
provided a further refinement and characterization of our model, which could
serve for a better understanding of the aetiology, pathogenesis and
pathophysiology of non-bacterial prostatitis.
PMID- 9649177
TI - Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular
carcinoma.
AB - Fas (APO-1/CD95)-mediated apoptosis plays an important role in liver cell
destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of
soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were
positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)
antibody. sFas levels were significantly higher in HCC patients (median 4.07
ng/ml; range 0.14-29.18 ng/ml) than levels in age-matched healthy donors (0.29
ng/ml; 0-4.90 ng/ ml) (P < 0.0001) and HBsAg or anti-HCV antibody-positive
patients with liver cirrhosis (LC) (2.16 ng/ ml; 0.24-8.39 ng/ml) (P = 0.0015).
An arbitrary cut-off level of 3.03 ng/ml (mean + 3 s.d. of controls) revealed the
positive frequency of sFas in each group: 1.7% in healthy subjects, 25.9% in LC,
and 59.0% in HCC (sensitivity 59.0% and specificity 74.1%). All HCC sera tested
contained transmembrane-deleted sFas and some contained another sFas lacking the
Fas C-terminal. The positive frequency of either sFas (59.0%) or alpha
fetoprotein (AFP) (57.4%) in HCC patients reached 77.0%. HCC patients with
multiple tumour foci (7.53 ng/ml; 1.40-29.18 ng/ml) had significantly higher sFas
levels than did patients with a solitary tumour (2.70 ng/ml; 0.14-19.0 ng/ml) (P
= 0.003). In all of the sFas-positive patients with a solitary tumour, surgical
removal of the tumour reduced sFas levels to the negative in the first post-op
week. These findings suggest that sFas may be closely linked with HCC and may be
a candidate for a clinical parameter for HCC.
PMID- 9649178
TI - Differential expression of cytokine transcripts in human epithelial ovarian
carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour,
tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour
cell lines.
AB - T cell lines derived in low concentrations of recombinant IL-2 (rIL-2) from TIL
of patients with epithelial ovarian carcinoma (EOC) often exhibit specific
cytotoxicity against autologous tumour cells. However, the ability of T cells at
the tumour site to respond to ovarian carcinoma cells may be affected by the
production of cytokines by the various cell types present. Using reverse
transcriptase-polymerase chain reaction (RT-PCR) we investigated cytokine
transcripts in: (i) established EOC tumour cell lines; (ii) solid tumour
specimens or peritoneal exudate cells (PEC) from ascites or peritoneal washings
of patients with EOC; and (iii) CD4+ TCRalphabeta+ and CD8+ TCRalphabeta+ TIL
derived T cell lines developed in rIL-2. We have found that (i) established EOC
tumour cell lines expressed transcripts for transforming growth factor-beta 2
(TGF-beta2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-gamma) (0/7) and
rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13),
and TGF-beta2 (12/13), and less often, IFN-gamma (3/13), whereas solid tumour
specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF
beta2 (4/8), and IL-10 (5/8), but not for IFN-gamma (0/8); (iii) CD4+
TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (4/4), IL-2 (4/4)
and IL-10 (3/4), whereas CD8+ TCRalphabeta+ T cell lines expressed transcripts
for IFN-gamma (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines
expressed TGF-beta2 transcripts. The frequency of IL-2 and TGF-beta2 transcripts
in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4+ or
CD8+ T cell lines expressing IFN-gamma, IL-2 and IL-10 transcripts were derived
in culture with rIL-2 from the TIL of specimens that did not necessarily express
these cytokines in the absence of rIL-2. The frequency of cytokine transcripts in
T cell lines compared with these same transcripts in the PEC was significantly
higher for IFN-gamma (P = 0.0005) and lower for TGF-beta2 (P = 0.0001). An
association was observed between the expression of cytokine transcripts in vivo
or by TIL-derived cell lines and functions exhibited by either production of
cytokines or in vitro cytotoxicity.
PMID- 9649179
TI - 1,25-Dihydroxyvitamin D3 restores sensitivity to cyclophosphamide-induced
apoptosis in non-obese diabetic (NOD) mice and protects against diabetes.
AB - The activated form of vitamin D, 1,25(OH)2D3, and its analogues can prevent type
I diabetes in NOD mice. Protection is achieved without signs of systemic
immunosuppression and is associated with a restoration of the defective immune
regulator system of the NOD mice. The aim of the present study was to investigate
whether this restoration of regulator cell function is the only mechanism in the
prevention of diabetes by 1,25(OH)2D3. We tested therefore if 1,25(OH)2D3 could
prevent cyclophosphamide-induced diabetes, since diabetes occurring after
cyclophosphamide injection is believed to be due to an elimination of suppresser
cells. NOD mice treated with 1,25(OH)2D3 (5 microg/kg every 2 days) from the time
of weaning were clearly protected against diabetes induced by cyclophosphamide
(200 mg/kg body wt at 70 days old) (2/12 (17%) versus 36/53 (68%) in control
mice, P < 0.005). By co-transfer experiments it was demonstrated that
cyclophosphamide had indeed eliminated the suppresser cells present in
1,25(OH)2D3-treated mice. Since cyclophosphamide injection did not break the
protection offered by 1,25(OH)2D3, it was clear that diabetogenic effector cells
were affected by 1,25(OH)2D3 treatment as well. This was confirmed by the finding
that splenocytes from 1,25(OH)2D3-treated mice were less capable of transferring
diabetes in young, irradiated NOD mice, and by the demonstration of lower Th1
cytokine levels in the pancreases of 1,25(OH)2D3-treated, cyclophosphamide
injected mice. This better elimination of effector cells in 1,25(OH)2D3-treated
mice could be explained by a restoration of the sensitivity to cyclophosphamide
induced apoptosis in both thymocytes and splenocytes, in normally apoptosis
resistant NOD mice. Altogether, these data indicate that the protection against
diabetes offered by 1,25(OH)2D3 may be independent of the presence of suppresser
cells, and may involve increased apoptosis of Th1 autoimmune effector cells.
PMID- 9649180
TI - Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class
I-deficient mice.
AB - GVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC
class I mismatching increases GVHD, but in MHC-matched BMT minor
histocompatibility antigens (mH) presented by MHC class I result in significant
GVHD. To examine the modification of GVHD in the absence of cell surface MHC
class I molecules, beta2-microglobulin-deficient mice (beta2m(-/-)) were used as
allogeneic BMT recipients in MHC- and mH-mismatched transplants. Beta2m(-/-) mice
accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H
2)-mismatched recipients developed acute lethal GVHD. In contrast, animals
transplanted across mH barriers developed indolent chronic disease that was
eventually fatal. Engrafted splenic T cells in all beta2m(-/-) recipients were
predominantly CD3+alphabetaTCR+CD4+ cells (15-20% of all splenocytes). In
contrast, CD8+ cells engrafted in very small numbers (1-5%) irrespective of the
degree of MHC mismatching. T cells proliferated against recipient strain antigens
and recognized recipient strain targets in cytolytic assays. Cytolysis was
blocked by anti-MHC class II but not anti-CD8 or anti-MHC class I monoclonal
antibodies (MoAbs). Cytolytic CD4+ T cells induced and maintained GVHD in mH
mismatched beta2m(-/-) mice, supporting endogenous mH presentation solely by MHC
class II. Conversely, haematopoietic beta2m(-/-) cells were unable to engraft in
normal MHC-matched recipients, presumably due to natural killer (NK)-mediated
rejection of class I-negative cells. Donor-derived lymphokine-activated killer
cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.
PMID- 9649181
TI - Phenotypic and functional modulation of T cells in vivo by extrathymic T cells
when T cells with MHC class II disparity were injected into athymic nude mice.
AB - TCRhigh cells are generated by the mainstream of T cell differentiation in the
thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in
the liver and by an alternative intrathymic pathway. It is still unknown how
these T cell populations interact in vivo with each other. To investigate the
interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude
(B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh
cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu
mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells
of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated
nude mice permitted a full expansion of TCRhigh cells which expressed the IL
2Ralpha+beta+ phenotype, namely, they were at the most activated state. These
mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other
hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor
origin and such TCRhigh cells continued to have the IL-2Ralpha(+/-)beta+
phenotype. These mice could survive but showed signs of chronic GVHD thereafter.
In both situations, CD4+alphabeta T cells expanded irrespective of donor or
recipient origin. These results suggest that TCRint cells in the recipient mice
possess a regulatory function in relation to donor TCRhigh cells; as a result,
fully activated TCRhigh cells acquired the IL-2Ralpha+beta+ phenotype and injured
the host, but TCRhigh cells suppressed in vivo remained as the IL-2Ralpha(+/
)beta+ phenotype and only partially injured the host.
PMID- 9649182
TI - Isolation and phenotypic characterization of colonic macrophages.
AB - Macrophages play an important role in the intestinal mucosal immune system.
However, they are a poorly defined cell population. We therefore determined their
phenotype in normal colonic mucosa. Macrophages were isolated from colonic
biopsies and surgical specimens by collagenase digestion. Colonic macrophages
were positively sorted by anti-CD33 magnetic beads. Flow cytometric triple
fluorescence analysis was applied to study CD14, CD16, CD33, CD44, CD11b, CD11c,
CD64, HLA-DR, CD80, CD86 and CD3/CD19 expression. CD33 was evaluated as a
positive marker for intestinal macrophages. CD33+ cells isolated from normal
colonic mucosa showed co-expression of the established intracellular macrophage
marker CD68 in FACS analysis. CD33+ cells were capable of phagocytosis. Isolation
of this cell population by magnetic anti-CD33 beads and culture resulted in a 4.2
40-fold increase in IL-1beta and 4.5-44-fold increase in tumour necrosis factor
alpha (TNF-alpha) secretion compared with unsorted lamina propria mononuclear
cells (LPMC). Of the CD33+ cells, 90.9 +/- 6.9% (mean +/- s.d.) were CD44+.
However, macrophages from colonic mucosa showed only a low expression of CD14
(10.5 +/- 3.8%), CD16 (10.1 +/- 3.9%), HLA-DR (27.3 +/- 9.2%), CD11b (17.4 +/-
6.8%), CD11c (17.8 +/- 10.4%). Furthermore, expression of CD80 (9.2 +/- 4.2%) and
CD86 (15.1 +/- 7.3%) was low, suggesting a low ability of normal intestinal
macrophages to activate T cells and T cell-mediated immune responses. We conclude
that CD33 is useful for the isolation and flow cytometric characterization of
colonic macrophages. These cells exhibit a single phenotype in normal mucosa
(CD33++, CD44++, CD14-, CD16-, CD11b-, CD11c-, HLA-DRlow, CD80-, CD86-) lacking
lipopolysaccharide (LPS) receptor and costimulatory molecules.
PMID- 9649183
TI - CD4+ T cells from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis
rodents migrate to the recipient's colon upon transfer; down-regulation by CD8+ T
cells.
AB - CD4+ T cells play an important role in the aetiology of inflammatory bowel
disease (IBD), but it is not clear which factor(s) cause activation of these
cells. The aim of this study was to examine the effects of adoptive transfer of
splenic (CD4+) T cells from TNBS/ethanol-sensitized donor rats to naive
recipients and the migration pattern of transferred T cells. For the transfer
experiments, colitis was induced in rats by colonic administration of
TNBS/ethanol. Seventeen days later, either total splenic T cells or CD4+, or CD8+
T cells were transferred to naive recipients. At days 1, 2 and 3 after transfer,
the recipients were killed and the migration pattern of the transferred T cells
was studied, as well as inflammatory cells in several organs, including the
colon. To determine cytokine profiles of the T cells, colitis was induced in
mice. Therefore, different combinations of 2,4-dinitrobenzene sulfonic acid
(DNBS) in ethanol or saline, or ethanol alone were intrarectally administered. At
day 9 after induction of colitis, mice were killed and cytokine profiles in the
colon were studied by reverse transcriptase-polymerase chain reaction (RT-PCR)
and immunohistochemistry. The results show that CD4+ T cells from donor rats with
TNBS/ethanol-induced colitis migrate in particular to the colon upon transfer to
naive recipients, and that this process is down-regulated by CD8+ T cells. This
migration is probably caused by T cell recognition of the colonic bacterial flora
and initiates an inflammatory reaction in the recipient's colon, characterized by
an increase of the recipient's own T cells, macrophages, and neutrophils. In the
mice experiments we showed that a second administration of DNBS/ethanol or
ethanol alone, which presumably causes bacterial translocation, results in
increased numbers of T cells into the colon, accompanied by an increase in Th1
cytokines. These data suggest that Th1 cells recognize the colonic bacterial
flora.
PMID- 9649184
TI - Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial
cells (iEC).
AB - Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of
them have a CD28- phenotype, the phenotype of effector cytotoxic T cells. We
asked whether the predominance of CD8+CD28- T cells in the gut may result from
peripheral blood T cells preferentially migrating to the iIEL compartment and
adhering to iEC. Compared with CD4 cells, adhesion of resting CD8+ T cells to iEC
cell lines was significantly higher. Adhesion could be blocked with a MoAb to
gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No
significant difference in the level of adhesion was observed between CD8+CD28+
and CD8+CD28- T cells. Thus CD8 cells may preferentially migrate to the iIEL
compartment, but loss of CD28 expression could occur in situ after migration.
Consistent with this hypothesis, the CD8+CD28- cells became enriched after co
culturing T cells with iEC cell lines and primary iEC. Induction of the CD8+CD28-
phenotype in cord blood and adult T cells was observed in co-cultures with iEC
and also with mitogens and superantigens. In the latter case, CD28 down
modulation was seen specifically in the Vbeta subset targeted by the
superantigen, indicating that loss of CD28 expression is a direct result of T
cell receptor (TCR)-mediated stimulation. The combined results suggest that
CD8+CD28- T cells are antigen experienced T cells, and that they may have a
survival advantage in the presence of gut epithelial cells in vitro. This may
contribute to the predominance of CD8+CD28- T cells in the iIEL compartment.
PMID- 9649185
TI - Decay-accelerating factor (DAF) in stool specimens as a marker of disease
activity in patients with ulcerative colitis (UC).
AB - Colonic epithelial cells of patients with UC express DAF in relation to the
severity of mucosal inflammation. The aim of this study was to determine whether
this factor in stool could be used as a marker of disease activity in UC
patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens
obtained from 55 patients with UC of various levels of disease activity. Stool
DAF concentrations in patients whose UC was active (0.0-785.6 ng/g stool; median
47.1 ng/g; n = 115) were significantly higher than concentrations in patients
whose disease was inactive (0.0-48.6 ng/g; median 0.0 ng/g; n = 66) (P < 0.0001).
Values in active UC patients also were higher than those in control patients with
diarrhoea (0.0-30.0 ng/g; median 0.0 ng/g; n = 26) (P < 0.0001) and in control
subjects without apparent colorectal disease (0-20.4 ng/g; median 0.0 ng/g; n =
44) (P < 0.0001). The elevated levels of stool DAF obtained from UC patients in
relapse declined markedly in specimens collected after the disease went into
remission following medical therapy. Stool DAF levels correlated with the
severity of endoscopic and histological findings and the degree of DAF expression
on the colonic epithelia. Our results suggest that the measurement of stool DAF
is useful as a non-invasive means of monitoring intestinal disease activity in
patients with UC.
PMID- 9649186
TI - Oxidative stress suppresses transcription factor activities in stimulated
lymphocytes.
AB - Effects of oxidative stress on stimulation-dependent signal transduction, leading
to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes
were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure
to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells
were then stimulated for 6 h. DNA-binding activities (determined by the
electrophoretic mobility shift assay) of three transcription factors: NFkappaB,
AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative
stress. The lymphocytes exhibited lipid peroxidation only upon exposure to the
lowest level of hydrogen peroxide used (20 microM). All three modes of oxidative
stress induced catalase activity in the lymphocytes. The only exception was
hydrogen peroxide at 20 microM, which did not induce catalase activity. We
conclude that: (i) suppression of specific transcription factor functions can
potentially serve as a marker of exposure to oxidative stress and its effects on
human lymphocytes; (ii) lipid peroxidation is only detectable in human
lymphocytes upon exposure to weak oxidative stress which does not induce catalase
activity; (iii) therefore, transcription factor DNA-binding activities are more
sensitive to oxidative stress than lipid peroxidation.
PMID- 9649187
TI - Somatic hypermutation of immunoglobulin genes is independent of the Bloom's
syndrome DNA helicase.
AB - Immunoglobulin gene somatic mutation leads to antibody affinity maturation
through the introduction of multiple point mutations in the antigen binding site.
No genes have as yet been identified that participate in this process. Bloom's
syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most
affected individuals exhibit an immunodeficiency of undetermined aetiology. The
gene for this disorder, BLM, has recently been identified as a DNA helicase. If
this gene were to play a role in immunoglobulin mutation, then people with BS may
lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin
genes generally produce low affinity antibodies, impaired helicase activity might
be manifested as the immunodeficiency found in BS. Therefore, we asked whether
BLM is specifically involved in immunoglobulin hypermutation. Sequences of
immunoglobulin variable (V) regions were analysed from small unsorted blood
samples obtained from BS individuals and compared with germ-line sequences. BS V
regions displayed the normal distribution of mutations, indicating that the
defect in BS is not related to the mechanism of somatic mutation. These data
strongly argue against BLM being involved in this process. The genetic approach
to identifying the genes involved in immunoglobulin mutation will require further
studies of DNA repair- and immunodeficient individuals.
PMID- 9649188
TI - Genetic identification of antigens exposed in damaged endothelial cells as
laminin-binding proteins.
AB - A monoclonal antibody, D5G2, which reacts in a balloon angioplasty damage model
with unfixed damaged but not with unfixed undamaged human endothelial cells, was
used to screen a human endothelial cDNA library in an Escherichia coli/lambda
gt11 expression system. Sequences of DNA inserts in D5G2+ phage clones matched
those reported for a laminin-binding protein, LBP-32. Both D5G2 and purified
laminin bound to a polypeptide of 55 kD on PVDF membranes carrying
electrophoretically separated endothelial cell lysates, D5G2 also bound to
recombinant LBP expressed in E. coli, and showed similar staining patterns on
human and bovine endothelial cells to another characterized anti-LBP antibody.
Increased staining of unfixed endothelial cells on detergent permeabilization
suggests that D5G2 binds to intracellular laminin-binding protein made accessible
by cell membrane injury. Antibodies to intracellular targets exposed by cell
damage may be useful in anchoring therapeutic agents at sites of vascular damage.
PMID- 9649189
TI - Sulphatide-binding properties are shared by serum amyloid P component and a
polyreactive germ-line IgM autoantibody, the TH3 idiotype.
AB - Serum amyloid P component (SAP) concentration was elevated in sera from leprosy
patients, significantly so above endemic controls in lepromatous cases. In the
sera of lepromatous leprosy (LL) patients who experienced an erythema nodosum
leprosum (ENL) episode the SAP fell at the onset of ENL and remained low
throughout, in two of three cases. Changes in SAP concentration parallel anti
sulphatide IgM concentrations. TH3, a monoclonal IgM germ-line antibody derived
from a LL patient, and SAP share similar binding patterns. In this study we
demonstrate binding to heparin and sulphatide. Moreover, SAP inhibited the
binding of TH3 to sulphatide, as well as anti-sulphatide IgM found in a range of
sera, and anti-sulphatide IgG in the only sera sample in which it was found. The
observation that anti-TH3 idiotype monoclonal and polyclonal anti-SAP antibodies
both inhibited the binding of TH3 and IgM in sera (but not IgG) to sulphatide
without binding to sulphatide themselves further demonstrated similar binding
specificities. The observations of similarity in binding reinforce ideas that SAP
may function as a primitive opsonin, but the clear ability to inhibit binding of
autoantibodies suggests that SAP may play a role in ameliorating tissue and
particularly nerve damage in leprosy patients.
PMID- 9649190
TI - Chemokines produced by mesothelial cells: huGRO-alpha, IP-10, MCP-1 and RANTES.
AB - Recently we showed the in vivo relevance of chemokines in cases of bacterial
peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients.
Mesothelial cells, the most numerous cells in the peritoneal cavity, are
hypothesized to function as a main source of chemokine production. We
investigated the time- and dose-dependent expression patterns of four chemokines
by mesothelial cells at the mRNA and protein level in response to stimulation
with physiological doses of proinflammatory mediators that are present at the
site of bacterial inflammation. Besides the chemokines huGRO-alpha (attractant
for neutrophils), MCP-1 and RANTES (monocyte attractants), the expression and
production of IP-10 was analysed. Mesothelial cells were cultured and stimulated
with either IL-1beta, tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma or
combinations of these. The time- and dose-dependent mRNA expression of the
chemokines was determined by Northern blot analysis and the protein production by
ELISA. It was concluded that mesothelial cells could indeed be triggered by the
mentioned stimuli to induce mRNA and protein production (huGRO-alpha and IP-10)
or to augment constitutive protein production (MCP-1). However, RANTES mRNA and
protein production could only be induced in some cases and only in small amounts.
The chemokine response of mesothelial cells was regulated differentially,
depending on the stimulus and the chemokine measured. In distinct cases,
combination of the stimuli led to synergy in mRNA expression and protein
production. The presented in vitro data support our hypothesis that mesothelial
cells in vivo are the main source of relevant chemokines in response to
proinflammatory mediators, suggesting an important role for mesothelial cells in
host defence.
PMID- 9649191
TI - Distinct modulation by interferon-gamma (IFN-gamma) of CD23 expression on B and T
lymphocytes of atopic subjects.
AB - The low-affinity IgE receptor (FcepsilonRII/CD23) plays a role in IgE production.
Cytokines participating in IgE synthesis also modulate CD23 expression on
lymphocytes, but whether this modulation is different in atopic subjects remains
unclear. We studied CD23 expression on B and T lymphocytes in 10 asthmatic
patients with Dermatophagoides pteronyssinus hypersensitivity and 10 healthy non
atopic subjects. Studies were performed by flow cytometry, in phytohaemagglutinin
(PHA) or IL-4-stimulated mononuclear cell cultures, alone or in the presence of
IFN-gamma. Soluble CD23 (sCD23) released in the culture supernatants was measured
by enzyme-linked immunoassay. Both PHA and IL-4 induced the expression of CD23 on
lymphocytes of atopic and non-atopic subjects. Whereas PHA increased both the
percentage and mean fluorescence intensity of CD23+ B and T cells, IL-4 alone did
not increase the percentage of CD23+ T cells. The effects of IFN-gamma were
different in both groups, since it was able to reduce the percentage of PHA
stimulated CD23+ T cells only in non-atopic individuals. In non-atopic subjects
more than atopic, levels of sCD23 were increased in the supernatants of PHA and
IL-4 cultures. These results show that the modulation of CD23 expression is
different on B and T cells, and that IFN-gamma acts differently in atopic and non
atopic individuals.
PMID- 9649192
TI - P-selectin requirement for neutrophil accumulation and injury in the direct
passive Arthus reaction.
AB - The aim of this study was to investigate the role of P-selectin in the
accumulation of neutrophils in the direct passive Arthus reaction in rat skin.
Direct passive Arthus dermal reaction was induced in male Sprague-Dawley (SD)
rats by a single i.v. injection of rat anti-sheep globulin (SG) 1 h before i.d.
injection of SG antigen. Anti-P-selectin or irrelevant control antibody was given
1 h before rat anti-SG injection. Complement depletion was also performed in a
separate group by pretreatment with cobra venom factor (CVF). In all groups
dermal swelling was assessed 4 h after antigen challenge. Four hours after
antigen challenge, rats treated with control antibody developed skin swelling
(2.29 +/- 0.47 mm), prominent complement deposition and neutrophil accumulation.
This response was associated with local up-regulation of endothelial P-selectin.
Pre-treatment with anti-P-selectin antibody 1 h before passive Arthus induction
prevented skin swelling (0.29 +/- 0.06 mm, P < 0.05, cf with control antibody
treatment), neutrophil accumulation and up-regulation of endothelial P-selectin
despite complement deposition. CVF treatment prevented complement deposition,
neutrophil accumulation and skin swelling (0.13 +/- 0.07 mm, P < 0.05, cf with
saline treatment). However, endothelial P-selectin expression was still present.
Inhibition of skin swelling and neutrophil accumulation in direct passive Arthus
by functional inhibition of P-selectin suggest a pivotal role for this adhesion
molecule in this inflammatory process. These results also suggest that multiple
steps are involved in the evolution of direct passive Arthus, including both P
selectin expression and complement activation. However, while complement
activation is essential for neutrophil accumulation and expression of dermal
injury, P-selectin up-regulation initiated by antibody/antigen deposition occurs
independently of complement activation.
PMID- 9649193
TI - Different susceptibilities of yeasts and conidia of Penicillium marneffei to
nitric oxide (NO)-mediated fungicidal activity of murine macrophages.
AB - Penicillium marneffei is an important opportunistic fungal pathogen. Host defence
mechanisms against P. marneffei are not fully understood. We investigated the
fungicidal activity of murine peritoneal macrophages against two forms of P.
marneffei, conidia and yeast cells, and the involvement of the NO-mediated
killing system. Peritoneal macrophages suppressed the intracellular growth of P.
marneffei yeast cells and conidia. The number of live yeast cells within
macrophages was significantly reduced by activation of macrophages by interferon
gamma (IFN-gamma), while a similar response was not observed with conidia. IFN
gamma-induced macrophage fungicidal activity against yeast cells was mediated by
NO and was almost completely inhibited by N(G)-monomethyl-L-arginine (L-NMMA), a
competitive inhibitor of NO synthesis, while N(G)-monomethyl-D-arginine (D-NMMA),
an optical isomer of L-NMMA, did not show any influence. NO production by
macrophages stimulated with IFN-gamma was significantly enhanced when these
macrophages were cultured with P. marneffei yeast cells, while conidia did not
enhance macrophage NO production. Furthermore, yeast cells were more susceptible
to the killing effect of chemically generated NO than conidia. Our results
indicate that the yeast form of P. marneffei is more sensitive to the fungicidal
activity of IFN-gamma-stimulated macrophages than conidia, and suggest that the
different effects of two forms of P. marneffei on macrophage NO production and
their different susceptibilities to NO may be reasons for the present findings.
PMID- 9649194
TI - Single-cell analysis of lymphokine imbalance in asymptomatic HIV-1 infection:
evidence for a major alteration within the CD8+ T cell subset.
AB - In this study we investigated at single-cell level by flow cytometry the
potential of T cell cytokine production in asymptomatic HIV-1-infected subjects
with > 200 CD4 counts and possible correlation with T helper cell depletion and
viral load. Mitogen-stimulated peripheral blood mononuclear cells from 32 HIV-1+
patients and 16 healthy subjects were intracytoplasmically stained for IL-2,
interferon-gamma (IFN-gamma), IL-4 or IL-10, and the frequency of cytokine
producing cells was assessed in total T cells, CD4, CD8 and CD45RO subsets as
well as in CD69+CD3+ gated lymphocytes. HIV-1+ patients, irrespective of their
degree of CD4 depletion, exhibited a major increase in IFN-gamma+ CD8 T cells,
largely due to CD28- cells, as well as a decrease in the capacity of CD8 T cells
to produce IL-2. Patients with > 500 CD4 counts showed a diminished frequency of
IL-4 expression in CD4 T cells and a negative correlation was found between this
parameter and the ex vivo CD4 counts in the 32 patients. Analysis of patients
stratified according to viral load revealed a significantly higher proportion of
IL-2-producing CD4 cells in the group with < 5000 RNA copies/ml. In short, using
single-cell analysis and an antigen-presenting cell-independent stimulus, we have
not been able to find any significant cytokine imbalances in the CD4 subset,
suggesting that the well described T helper defects are not due to intrinsic
alterations in the potential of CD4 T cells to produce cytokines. On the other
hand, the major disturbances in the CD8 T lymphocytes agree with the marked
activation and possible replicative senescence of CD8 T cells and emphasize the
role of this subset in HIV immunopathogenesis.
PMID- 9649195
TI - Increased eosinophil activity in acute Plasmodium falciparum infection-
association with cerebral malaria.
AB - To assess the eosinophil response to Plasmodium falciparum infection a cohort of
initially parasite-free Ghanaian children was followed for 3 months. Seven of
nine children who acquired an asymptomatic P. falciparum infection showed
increase in eosinophil counts, while a decrease was found in seven of nine
children with symptomatic malaria, and no change was observed in 14 children who
remained parasite-free. In a hospital-based study, paediatric patients with
cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had
uniformly low eosinophil counts during the acute illness followed by eosinophilia
30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and
eosinophil protein X (EPX) were measured as indicators of eosinophil activation.
In spite of the low eosinophil counts, ECP levels were increased on day 0 and
significantly higher in patients with CM (geometric mean (95% confidence
interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and
UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found
for EPX. It thus appears that the low eosinophil counts may be due to tissue
sequestration and destruction rather than decreased production. The plasma levels
of the granule proteins correlated with levels of tumour necrosis factor and
soluble IL-2 receptor, implicating inflammatory responses and T cell activation
as causes of the eosinophil activation. By contrast, the eosinophil induction did
not appear to be part of a Th2-like response. Eosinophil granule proteins may be
important in both control of malaria infection and the pathogenesis of severe
malaria.
PMID- 9649196
TI - Down-regulation of MHC class II molecules and inability to up-regulate class I
molecules in murine macrophages after infection with Toxoplasma gondii.
AB - Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage
lineage and replicates within a parasitophorous vacuole. Since macrophages may
activate specific T lymphocytes by presenting pathogen-derived antigens in
association with molecules of the MHC, we investigated the in vitro expression of
host cell molecules involved in antigen processing and presentation before and
during infection of murine bone marrow-derived macrophages (BMM) with T. gondii.
Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to
host ratios, up-regulation of total MHC class II molecules by interferon-gamma
(IFN-gamma) was dose-dependently abrogated in up to 50% of macrophages compared
with uninfected control cultures. Quantitative analyses by flow cytometry
revealed that the IFN-gamma-induced surface expression of class II antigens as
well as the IFN-gamma-induced upregulation of class I molecules was significantly
decreased in T. gondii-infected macrophage cultures compared with uninfected
controls. However, the constitutive expression of MHC class I antigens was not
altered after parasitic infection, and infected BMM remained clearly positive for
these molecules. After infection of macrophages preactivated with IFN-gamma for
48 h, T. gondii also actively down-regulated an already established expression of
MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction
in intracellular and plasma membrane-bound class II molecules started
approximately 20 h after infection. While MHC class II antigens were most
prominently reduced in parasite-positive host cells, culture supernatant from T.
gondii-infected BMM cultures also significantly inhibited expression of these
molecules in uninfected macrophages. However, down-regulation of MHC class II
molecules was not mediated by an increased production of prostaglandin E2, IL-10,
transforming growth factor-beta or nitric oxide by infected BMM compared with
uninfected controls. Our data indicate that intracellular T. gondii interferes
with the MHC class I and class II antigen presentation pathway of murine
macrophages and this may be an important strategy for evasion from the host's
immune response and for intracellular survival of the parasite.
PMID- 9649197
TI - Abnormal T cell responses to bacterial superantigens in Behcet's disease (BD).
AB - This study examines the nature of T cell hypersensitivity in BD. Highly purified
T cells from 32 BD patients, from 29 rheumatoid arthritis (RA) patients and from
14 healthy individuals were cultured with various concentrations of
Staphylococcal enterotoxins (SE) B and C1 in the presence of monocytes for 5
days, after which the production of interferon-gamma (IFN-gamma) was assessed.
High concentrations of SE (1 ng/ml) stimulated BD T cells as well as control T
cells to produce comparably high amounts of IFN-gamma, whereas low concentrations
of SE (1 pg/ml) stimulated BD T cells much more effectively than normal or RA T
cells. The hypersensitivity of BD T cells to low concentrations of SEC1 was
restored with RA monocytes instead of BD monocytes, whereas BD monocytes could
not elicit the SEC1-induced IFN-gamma production of RA T cells. Moreover, there
were no significant differences between BD T cells and RA T cells in monocyte
independent IFN-gamma production stimulated with low or high concentrations of
immobilized anti-CD3, or in the monocyte-mediated enhancement of IFN-gamma
production stimulated with a low concentration of immobilized anti-CD3. These
results confirm that T cell hypersensitivity is not confined to certain specific
antigens in BD. More importantly, the data strongly suggest that abnormalities in
signal transduction triggered by perturbation of T cell receptors, but not in
that induced by cross-linking of CD3 molecules nor in that delivered through
costimulation molecules, play an important role in the pathogenesis of BD.
PMID- 9649198
TI - Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I
(beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid
antibodies on the protein C system.
AB - It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant
activity of the protein C system, but the mechanism is still obscure. In this
study, we demonstrate that anticardiolipin antibodies (not anti-protein C
autoantibodies) can bind protein C via beta2-GPI, which bears their binding
epitope, in a fashion dependent on negatively charged phospholipids. We studied
the binding of IgG from aPL to protein C in the presence of beta2-GPI by ELISA
(anti-'protein C' antibody ELISA), and compared their binding with those obtained
in the absence of beta2-GPI. In the anti-'protein C' antibody ELISA system, 47%
of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and
beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly
significant correlations were found between the titre of anti-'protein C'
antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r =
0.802, P = 0.0001). We further analysed the interaction between protein C,
phospholipids, beta2-GPI and human aCL MoAbs established from patients with
antiphospholipid syndrome. In a first set of experiments, the binding of beta2
GPI to protein C and its phospholipid dependency were investigated. Beta2-GPI
bound to protein C in the presence of CL or phosphatidylserine, but not in the
presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of
experiments, the binding of three human monoclonal aCL recognizing the cryptic
epitope of beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated in the
presence of cardiolipin and beta2-GPI. All three human monoclonal aCL bound to
protein C in the presence of CL and beta2-GPI, whereas they did not in the
absence of either beta2-GPI or CL. These data suggest that protein C could be a
target of aCL by making a complex with CL and beta2-GPI, leading to protein C
dysfunction.
PMID- 9649199
TI - Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte
function and receptor expression in patients with ventilator-dependent pneumonia.
AB - Considerable experimental evidence in animals suggests that treatment with G-CSF
may have a beneficial effect in the management of severe infections in non
neutropenic hosts. This beneficial effect is attributed to an enhancement of
granulopoiesis and neutrophil function, the latter possibly involving up
regulation of receptors on neutrophils that are involved in antibody-mediated
cytotoxicity and killing of microorganisms. We compared neutrophil function and
phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with
severe ventilator-dependent pneumonia, at baseline and following initiation of G
CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with
three-fold increased blood neutrophil counts at day 3 of treatment compared with
baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml.
After correction for lavage dilution effects, BALF G-CSF levels did not differ
significantly from baseline, nor did neutrophil receptor expression (FcgammaRI,
FcgammaRII, FcgammaRIII, CR3, and L-selectin) or indicators of neutrophil
function such as respiratory burst activity, phagocytosis and killing of Candida
albicans in BALF or blood. The mortality in this group of patients was 30% and
compared favourably to the APACHE II-derived predicted mortality of 60%. We
conclude that the possible therapeutic benefit of G-CSF administration in the
early phase of severe bacterial pneumonia is not readily explained by its effect
on baseline indicators of neutrophil function or receptor expression.
PMID- 9649200
TI - Induction of unresponsiveness against IgA in IgA-deficient patients on
subcutaneous immunoglobulin infusion therapy.
AB - Patients with IgA deficiency often demonstrate circulating antibodies against
IgA, which have been suggested to be associated with transfusion reactions. Sera
from three patients with common variable immunodeficiency (CVID) and one with a
selective IgA deficiency with anti-IgA antibodies receiving subcutaneous
gammaglobulin replacement therapy were analysed for serum levels of IgG, IgA and
anti-IgA before and during a treatment period of 4-7 years. Treatment with
gammaglobulin preparations containing significant amounts of IgA (< 5 mg/ml)
resulted in a decrease or disappearance of the anti-IgA antibodies. Analysis of
serum fractions, however, revealed anti-IgA activity in the complex-containing
fractions. In vitro experiments gave similar results with a shift of anti-IgA
activity from the monomeric to the complex-containing fractions (that could not
be detected in whole serum). When the patients were subsequently switched to
treatment with a preparation containing less IgA (< 80 microg/ml) or made an
interruption in the treatment schedule, the anti-IgA antibodies reappeared.
Importantly, however, one of the patients lost his anti-IgA activity during a 3
month period on the preparation containing the higher IgA levels, and these
antibodies did not reappear after switching to the low IgA-containing
preparation. After 5 years on this preparation, anti-IgA can still not be
detected, suggesting induction of unresponsiveness.
PMID- 9649201
TI - Increase in dendritic cell numbers, their function and the proportion uninfected
during AZT therapy.
AB - The effects of AZT treatment on the numbers, level of infection and function of
peripheral blood dendritic cells (DC) were examined in patients with HIV
infection. This was a cross-sectional study of patients before AZT treatment and
up to 20 months after initiation of treatment. Numbers of DC separated by density
gradients were below the normal range in patients before treatment, but increased
between 3 and 12 months of treatment. The numbers of DC per provirus copy rose
from around 100 cells to 5000 cells and this decrease in viral load in DC was
significant between 3 and 20 months of treatment. The capacity of DC to stimulate
allogeneic T cell proliferation was low before treatment and significantly higher
between 6 and 12 months after the start of AZT. This study indicated that AZT
treatment produced beneficial effects on DC by increasing their numbers, reducing
the provirus load and increasing their function in stimulating T cells. These
results support the thesis that the function of these potent antigen-presenting
cells is important in development of immunological defects in AIDS, and that
effects of AZT treatment on DC may provide a measure of its therapeutic effect.
PMID- 9649202
TI - Cloning and characterization of a latex allergen (Hev b 7): homology to patatin,
a plant PLA2.
AB - We previously identified a 46-kD protein allergen in latex as having amino acid
sequence homology to the patatin gene family. The objective of this study was to
characterize this protein by molecular techniques. RNA was isolated from the
latex or leaf material from Hevea brasiliensis and from potato tubers. Specific
polymerase chain reaction (PCR) primers were designed from the amino acid
sequence and reverse transcriptase (RT)-PCR amplified a specific product from
latex RNA that was subsequently cloned and sequenced. This product was 1493 bp in
length with an 1167 bp open reading frame. The deduced amino acid sequence
encodes for a 389 aa protein, pI 4.82 with 43% homology to tobacco patatin.
Northern analysis of potato, Hevea leaf, and latex RNA demonstrated the message
to be most abundant in latex, weakly present in Hevea leaf, but no hybridization
occurred with potato RNA. Patatin has lipid acyl-transferase and PLA2-like
activity, suggesting it plays a role as a defence-related protein. Other defence
related proteins in latex such as hevein, glucanase, and hevamine are also
allergens. Increased production of defence-related proteins as a result of
increased tapping of the rubber trees to meet the demand for latex may explain
the increased allergenicity of latex.
PMID- 9649203
TI - T cell receptor (TCR) Vbeta gene usage in bronchoalveolar lavage and peripheral
blood T cells from asthmatic and normal subjects.
AB - T cells are thought to play an important regulatory role in asthma, but little is
known about the T cell repertoire of the human lung or whether asthma is
associated with any specific repertoire changes. Flow cytometry and MoAbs to TCR
VB (TCRBV) families were used to quantify bronchoalveolar lavage (BAL) and blood
T cells from normal and atopic individuals. Clonality was then assessed by
polymerase chain reaction (PCR) amplification of cDNA and gene scanning using
consensus and family-specific TCRBV primers and confirmed by sequence analysis.
In addition, blood and BAL T cell populations were studied pre- and post-allergen
challenge in four patients with allergic asthma. The majority of TCRBV families
detected in blood by MoAb staining were also represented in BAL. While
differences between BAL and blood populations were evident in each individual
studied, these differences were not consistent between individuals or between
CD4+ and CD8+ T cell subpopulations. These results are in broad agreement with
other published studies, but in contrast to previous work we found a consistent
difference between TCRBV7 family usage in blood and BAL in all individuals
studied, and a consistently increased proportion of CD4+ BAL T cells bearing
BV5S2/3 in asthmatics only. After allergen challenge, the pattern of TCRBV gene
usage was largely unchanged as judged by flow cytometry. Gene scanning of PCR
products generated from consensus VB primers revealed polyclonal lymphocyte
populations in blood and BAL from all seven atopic individuals: in one normal
tested polyclonal populations were found in blood and oligoclonal populations in
BAL. Selected families amplified with family-specific primers BV5S2/3, BV6 and
BV7 (chosen because of their predominance in BAL compared with blood) were more
variable and revealed predominant polyclonal populations in blood and polyclonal
or oligoclonal populations in BAL. In one asthmatic patient a clonal BV5S2 family
was found in BAL. Following allergen challenge there were no significant changes
in polyclonality/oligoclonality/clonality in three cases, but in one case a
clonal BV5S2 population was found after challenge, that had not been evident
beforehand. The lung T cell repertoire is thus broadly representative of blood T
cells, but shows population differences that may result from response to
persistent exposure to airborne antigens common to normal and atopic individuals.
Oligoclonal TCRBV family expansion appears to be primarily lung-specific but
independent of atopic asthma, although our challenge data in one case support the
concept that clonal populations may follow local allergen challenge. These data
are consistent with selection and amplification of specific T cell families in
the lung in response to local antigenic exposure.
PMID- 9649204
TI - Immunity to type IX collagen in rodents: a study of type IX collagen for
autoimmune and arthritogenic activities.
AB - Type IX collagen (CIX), a cartilage-specific glycoprotein, constitutes < or = 10%
of cartilage collagen. To ascertain whether CIX can induce arthritis as shown for
type II and XI collagen (CII and CXI), outbred rats were sensitized with bovine,
chick and human CIX; inbred rats, mice, and guinea pigs were sensitized with
bovine CIX. Mice and guinea pigs proved resistant to arthritis, as did rats
sensitized with CIX/Freund's incomplete adjuvant (FIA). Arthritis was seen in
rats when 100 microg of Mycobacterium tuberculosis (Mtb) were added to FIA, but
seldom with smaller doses of Mtb, suggesting the arthritis was adjuvant-induced.
High levels of antibodies to rat CIX, containing complement-fixing subclasses,
were detected in rat sera in addition to DTH and lymphocyte proliferation
responses to rat CIX. Given the potential for CIX-induced disease, CIX-sensitized
rats were injected intraperitoneally with lipopolysaccharide (LPS) to stimulate
proinflammatory cytokine release, and intra-articularly with rat CIX to stimulate
arthritis. LPS stimulation was ineffective; however, intra-articularly injected
CIX produced transient synovitis. When rats with stable adjuvant arthritis were
sensitized with CIX/FIA, significant increases in paw volume were measured
compared with controls given CI/FIA. Immunohistochemical studies of actively and
passively sensitized rats revealed deposits of CIX antibody, but not C3, at the
joint margins where proteoglycan staining was weak. Together, these findings
suggest that autoimmunity to CIX, in contrast to CII and CXI, is not directly
pathogenic but may contribute to joint injury provided arthritis is initiated by
an independent disease process.
PMID- 9649205
TI - Endogenous glucocorticoids modulate neutrophil migration and synovial P-selectin
but not neutrophil phagocytic or oxidative function in experimental arthritis.
AB - Pharmacologic glucocorticoids are powerful inhibitors of the inflammatory
response at many levels, including leucocyte trafficking and function. The
adhesion molecule P-selectin is a key participant in polymorphonuclear neutrophil
(PMN) migration to sites of inflammation. The extent to which endogenous
glucocorticoids influence PMN migration and activation is not clear. We used the
glucocorticoid receptor antagonist RU486 to examine the effect of endogenous
glucocorticoid blockade on PMN migration and function in carrageenan
monoarthritis in the rat. Arthritis was induced by intraarticular injection of
carrageenan and disease severity measured by PMN count in synovial lavage fluid.
Decalcified frozen sections of injected joints were analysed for expression of P
selectin by immunohistochemistry. Adrenal glucocorticoid action was blocked in
vivo with RU486 20 mg/kg. PMN phagocytosis and reactive oxygen species synthesis
were measured by flow cytometry. Carrageenan injection was associated with severe
arthritis (synovial lavage PMN 5.9 +/- 0.7 x 10(6), P < 0.01 versus control)
which was dose-dependent. P-selectin was not detected in normal joints but was
abundant in joints injected with 500 microg carrageenan. RU486 resulted in
exacerbation of carrageenan arthritis (9.7 +/- 0.8 x 10(6), P < 0.05). RU486 also
altered the threshold for disease induction, in that most RU486-treated animals
were susceptible to arthritis at a dose of carrageenan (2.5 microg) which did not
induce arthritis in most control-treated animals (P < 0.05), denoting an altered
threshold for arthritis induction. RU486 treatment was associated with increased
synovial P-selectin expression. Activation status as measured by PMN phagocytic
and oxidative function were not influenced by endogenous glucocorticoid blockade.
These findings suggest that endogenous glucocorticoids selectively influence PMN
migration to inflamed joints via P-selectin expression, but have no effect on PMN
activation status.
PMID- 9649206
TI - Augmented levels of macrophage and Th1 cell-related cytokine mRNA in
submandibular glands of MRL/lpr mice with autoimmune sialoadenitis.
AB - MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflammation of
the salivary and lachrymal glands resembling Sjogren's syndrome (SS),
representing an animal model to study this disease. We used in situ hybridization
with synthetic radiolabelled oligonucleotide probes to examine expression of mRNA
encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4
and 5-month-old MRL/lpr mice. Phenotypic composition of submandibular gland
infiltrates was evaluated by immunohistochemistry. Cells expressing tumour
necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-12 mRNA were strongly up
regulated at about the time of onset of sialoadenitis, suggesting a role of these
cytokines in development of the disease. Interferon-gamma (IFN-gamma) and
cytolysin mRNA-expressing cells were gradually up-regulated over the disease
course up to 5 months of age, the time when sialoadenitis is at its height,
favouring a role of these cytokines in progression of the disease as well. Low
levels of IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing
cells were observed at 2, 3 and 4 months of age, and were almost undetectable at
5 months. Maximum levels of CD4+, CD8+ and interdigitating/dendritic cells, as
well as of MHC class II and MHC class I expression were seen at 3 months, with
CD4+ outnumbering CD8+ cells. Maximum levels of macrophages were seen at 4 months
of age. These data argue for a major role of the proinflammatory cytokines TNF
alpha, IL-1beta, IL-6, IL- 12, IFN-gamma and cytolysin in initiation and
perpetuation of autoimmune sialoadenitis in MRL/lpr mice, probably in conjunction
with an insufficiency of the anti-inflammatory cytokines TGF-beta and IL-10.
PMID- 9649207
TI - IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W
F1 mice.
AB - In the present study, we examined the preventive effect of anti-mouse IL-6
receptor (IL-6R) antibody, MR16-1, on the development of autoimmune kidney
disease in female NZB/W F1 (BWF1) mice. Immunological tolerance to MR16-1 or
isotype-matched control antibody, KH-5, was induced by the simultaneous
administration of anti-CD4 MoAb in mice. Thereafter, mice were intraperitoneally
given 0.5 mg of MR16-1, 0.5 mg of KH-5 or saline once a week from 13 to 64 weeks
of age. MR16-1 treatment dramatically suppressed proteinuria and prolonged the
survival time of BWF1 mice. Only one out of 10 mice died with high levels of
proteinuria throughout the experiment. MR16-1 almost completely suppressed the
production of IgG forms of anti-DNA and anti-TNP antibodies, but not the IgM
forms of these antibodies. In particular, all IgG subclasses (IgG1, IgG2a, IgG2b
and IgG3) of anti-DNA antibody production were significantly suppressed.
Moreover, serum IgG1, IgG2a and IgG3 levels in MR16-1-treated mice were lower
than those in saline- and KH-5-treated mice, whereas serum IgM and IgA levels
were not influenced. In conclusion, MR16-1 potently suppressed the development of
autoimmune disease in BWF1 mice, and this was attributed to its effect of
specific suppression of IgG class antibody production.
PMID- 9649208
TI - Tumour-specific cytotoxic T lymphocyte activity in Th2-type Sezary syndrome: its
enhancement by interferon-gamma (IFN-gamma) and IL-12 and fluctuations in
association with disease activity.
AB - Sezary syndrome (SzS) is the leukaemic variant of cutaneous T cell lymphoma
(CTCL), whose malignant T cells are of the Th2 type in most cases. In this study
we investigated the tumouricidal activity of cytotoxic T lymphocytes (CTL)
present in peripheral blood of a patient with Th2-type SzS, focusing on the
effect of IL-2, IFN-gamma and IL-12 on their cytotoxic activity, and the
relationship between their lytic capacity and the patient's clinical course. At
four different time points during a 2-month clinical period, CD4+CD7- Sezary
cells and CD8+ cells were separated from the patient's circulating cells. CD8+
cells were cultured with chemically attenuated, purified Sezary cells in the
presence of IL-2 to develop specific cytotoxicity. The CD8+ cells thus cultured
exhibited lytic activity against autologous Sezary cells. Concomitant addition of
IFN-gamma or IL-12 exerted a synergistic cytolytic effect with IL-2 on the tumour
cells. Cytotoxicity inhibition studies using MoAbs revealed that the cytotoxicity
operated in MHC class I-, CD8- and alphabeta T cell receptor-dependent manners.
Furthermore, eight CD8+ T cell clones generated from cultured CD8+ cells
exhibited a strong cytotoxicity against Sezary cells in an MHC class I-restricted
fashion. During the clinical course, the activity of generated CTL and the number
of CD8+ cells were inversely correlated with disease activity as assessed by the
serum level of lactate dehydrogenase. These findings suggest that CTL down
regulate the growth of malignant T cells in this long-standing disease. Since Th2
cytokines such as IL-4 down-modulate CTL activity, CTL are assumed to be usually
suppressed in SzS, whose malignant T cells are of Th2 type. It is likely that the
administration of IFN-gamma normalizes this Th2-skewing state, activates CTL, and
thus exerts the therapeutic effectiveness in the treatment of CTCL.
PMID- 9649209
TI - Normal and clonal B lineage cells can be distinguished by their differential
expression of B cell antigens and adhesion molecules in peripheral blood from
multiple myeloma (MM) patients--diagnostic and clinical implications.
AB - Human MM is a haematologic disorder characterized by the accumulation of
malignant plasma cells (PC), primarily in the bone marrow (BM). Although these
cells characteristically home to the BM, in recent years several groups have
detected the presence of related malignant B cells in the peripheral blood (PB)
which could be implicated in the progression and spread of the disease. However,
the proportion and origin of these clonotypic circulating B cells is still
controversial. In this study, using a triple-staining flow cytometric procedure
and a whole blood lysis method, PB B lineage cells could be divided into two
populations according to their distinct repertoires of cell adhesion molecules
and B cell antigens in untreated MM patients. The results show that: (i) the
percentage and the absolute number of PB CD19+ B cells were decreased in MM
patients compared with controls; (ii) the quantity and percentage of B cell
antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (beta1- and beta2
integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19+ cells of
MM patients and healthy subjects were similar and all of them were virtually
polyclonal cells; (iii) a very minor circulating CD19-CD38++CD45-/dim subset was
also detected which expressed CD138 (B-B4) (high intensity), monoclonal
cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19,
CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such
as CD62L, CD18 and CD11a; this CD19-CD38++CD45-/dim CD138++ subset was not found
in normal blood and exhibited a phenotypic profile which was closely related to
that of malignant BM plasma cells, with the exception of the CD56 antigen.
Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements
confirmed these results. We postulate that, in MM patients, circulating B lineage
cells may be divided into two different categories: polyclonal CD19+ B cells and
a very minor proportion of clonal CD138++ PC that escape from the BM.
PMID- 9649210
TI - Neoplastic thymic epithelial cells of human thymoma support T cell development
from CD4-CD8- cells to CD4+CD8+ cells in vitro.
AB - Human thymoma is a thymic epithelial cell tumour which often contains a large
number of immature T cells and is frequently associated with autoimmune diseases.
Since thymic epithelial cells play key roles in the development and selection of
T cells in the normal thymus, we hypothesized that the neoplastic thymic
epithelial cells of thymoma may support T cell differentiation in the tumour. We
characterized CD4-CD8- cells in thymoma and applied an in vitro reconstitution
culture system using the CD4-CD8- cells and the neoplastic epithelial cells
isolated from thymoma. CD34, a stem cell marker, was expressed on 29.9 +/- 12.2%
of CD4-CD8- cells in thymoma. TCRgammadelta was expressed on 27.4 +/- 15.1% of
CD4-CD8- cells and CD19, a B cell marker, was expressed on 14.1 +/- 23.1% of CD4
CD8- cells. CD4-CD8- cells expressed both IL-7R alpha-chain and common gamma
chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic
epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single
positive intermediates was observed within 9 days' co-culture in the presence of
recombinant IL-7. Furthermore, we examined the reconstitution culture using
CD34+CD4-CD8- cells purified from normal infant thymus. The CD34+CD4-CD8- cells
in normal thymus also differentiated to CD4+CD8+ cells in the allogeneic co
culture with the neoplastic epithelial cells of thymoma. These results indicate
that the tumour cells of thymoma retain the function of thymic epithelial cells
and can induce differentiation of T cells in thymoma.
PMID- 9649211
TI - Analysis of orbital T cells in thyroid-associated ophthalmopathy.
AB - Thyroid-associated ophthalmopathy (TAO) has a major effect on the two
compartments of the retro-orbital (RO) space, leading to enlargement of the
extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue
is a characteristic feature of TAO and there is current interest in whether these
T cells are specifically and selectively reactive to RO tissue itself. We
recently established 18 T cell lines (TCL) from RO adipose/connective tissue of
six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated
autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T
cells reactive to autologous RO tissue protein fractions. Here we report on the
phenotype characteristics and cytokine gene expression profiles of these orbital
TCL and on their immunoreactivity to the organ-specific thyroid antigens
thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG).
Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three
being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse
transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression
revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL),
interferon-gamma (IFN-gamma) (n = 10), tumour necrosis factor-beta (TNF-beta) (n
= 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-alpha (n = 12) and IL-10
(n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other
16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were
predominantly CD4+ there were no significant relationships between TCL phenotype,
cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare)
occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine
gene expression in all RO tissue-reactive TCL support the concept that TAO is a
tissue-specific autoimmune disease, distinct immunologically from the thyroid,
and involving both T cell and B cell autoimmune mechanisms in disease
pathogenesis.
PMID- 9649213
TI - A pancolitis resembling human ulcerative colitis (UC) is induced by CD4+ TCR
alphabeta T cells of athymic origin in histocompatible severe combined
immunodeficient (SCID) mice.
AB - CD4+ TCRalphabeta+ T cells from the colonic lamina propria of athymic (nude) mice
were adoptively transferred into histocompatible (SCID) mice homozygous for the
autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of
these extrathymic CD4+ T cells into SCID mice induced a pancolitis in the
adoptive host. The histopathology of this inflammatory response was restricted to
the colon and closely resembled human UC. CD4+ T cells infiltrating the colonic
lamina propria of diseased SCID mice displayed the surface phenotype of mucosa
seeking memory/effector cells, expressed interferon-gamma (IFN-gamma), and lysed
targets in a Fas (CD95)/FasL-dependent pathway. Massive accumulation of
oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1
memory/effector T cells in the colonic lamina propria of a histocompatible,
immunodeficient host elicits a pancolitis that morphologically mimics human UC.
PMID- 9649212
TI - Colonic explant production of IL-1and its receptor antagonist is imbalanced in
inflammatory bowel disease (IBD).
AB - IBD is associated with an increased activation of intestinal immune cells, which
causes overproduction of proinflammatory cytokines such as IL-1beta. IL-1beta is
implicated in mediating the sustained inflammatory response. IL-1 receptor
antagonist (IL-1Ra), the naturally occurring inhibitor of IL-1, has been shown to
have beneficial effects in experimental models of colitis. In this study we
investigated the hypothesis that an imbalance between IL-1 and IL-1Ra exists in
IBD by measuring their secretion by explant cultures of colonic biopsies. Freshly
homogenized biopsies from involved tissue in IBD patients exhibited significantly
lower IL-1Ra/IL-1beta ratios than control and uninvolved IBD mucosal tissue.
Using explant cultures, in vitro production of IL-1beta and IL-1Ra increased
progressively during the 4-18-h culture periods. IL-1beta secretion was higher in
supernatants from involved Crohn's disease (CD) and ulcerative colitis tissue
compared with control tissue, and IL-1beta levels increased with severity of
inflammation. IL-1Ra secretion was not elevated in involved IBD samples, but
significantly higher levels were released when moderate to severely involved
tissue samples were compared with noninflammatory controls. Similar to freshly
homogenized tissue, explant studies showed that the IL-1Ra/IL-1beta ratios were
significantly decreased in involved IBD tissue, but not in uninvolved CD or
inflammatory control specimens. These data support the hypothesis of an imbalance
between IL-1beta and IL-1Ra in IBD.
PMID- 9649214
TI - Detection and characterization of antibodies specific to food antigens (gliadin,
ovalbumin and beta-lactoglobulin) in human serum, saliva, colostrum and milk.
AB - Antibodies against food antigens are usually produced in healthy people. This
humoral response can be detected both in serum and secretions. The
characterization of this response can be useful for a better understanding of
food-related immunological alterations. In this study, IgA and IgG antibodies
specific to ovalbumin, beta-lactoglobulin or gliadin were measured in serum,
saliva, colostrum and milk from 40 healthy breast-feeding women. Specific IgA and
IgG to the three antigens were measured by indirect ELISA. Specific IgG levels
were highest in serum and very low in the other biological fluids. No correlation
between the IgG specific to the different antigens was found. Specific IgA
reactivity was found in all the samples analysed. Levels observed were higher in
colostrum and milk than in serum and saliva. In spite of being three different
unrelated food antigens, a correlation between the levels of specific IgA was
found in saliva, colostrum and milk samples of all subjects studied. The
specificity of IgA anti-gliadin antibodies from serum, saliva and colostrum was
analysed by immunoblotting of SDS-PAGE-separated wheat proteins. Each sample
presented a unique pattern of recognition. No common pattern of recognition was
found either among the same biological fluids of the different subjects tested,
or among the different samples--either serum, colostrum or saliva--of the same
individual. Different degrees of specificity to wheat proteins among IgA from
colostrum, saliva or serum were observed, suggesting that the local IgA-producing
populations are functionally different in the different tissues of the organism.
PMID- 9649215
TI - Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood.
AB - Although in cord blood (CB) transplantation graft-versus-host disease (GVHD) is
reported to be less severe, GVHD may occur even in patients with HLA-identical
sibling donors. This result shows that HLA typing can not entirely predict GVHD.
The standard MLR with CB cells was either normal or slightly reduced compared
with adult peripheral blood (PB) cells. We used two manipulations to increase the
responses of CB cells to allo-antigens. The first was to treat the stimulator
cells with cytokines, and the second to amplify weak proliferative responses by
adding exogenous cytokines to MLR cultures (modified MLR). The stimulator cells
were treated with both interferon-gamma (IFN-gamma) and IL-4. The responder cells
were treated with both IL-2 and tumour necrosis factor-alpha (TNF-alpha). It is
still to be determined whether or not this cytokine-enhanced MLR could be a
possible predictor of GVHD. However, using these cytokines, 90% of CB could
recognize allo-antigens, even if the standard MLR was negative.
PMID- 9649216
TI - Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1
or ELAM-1 expression by human vascular endothelial cells.
AB - A previous study reported that intercellular adhesion molecule-1 (ICAM-1)
expression by human vascular endothelial cells (HUVEC) is augmented by
intracellular signal transmission mainly through the protein kinase C (PKC)
system stimulated by TXA2 receptors. In the present study, we show that a TXA2
receptor agonist, U46619, augments the expression of not only ICAM-1, but also
vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion
molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with
SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the
extent of U46619-induced mRNA accumulation and surface expression of the adhesion
molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC,
diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB
and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM
1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or
ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by
induction of NF-kappaB and AP-1 binding activity through the PKC system, and that
VCAM-1 expression is augmented by induction of NF-kappaB binding activity.
PMID- 9649217
TI - Autoantibody prevalence in children with liver disease due to chronic hepatitis C
virus (HCV) infection.
AB - HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with
autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection
or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence
of tissue autoantibodies in 51 children with chronic HCV infection and 84 with
other CLD was analysed by standard techniques. Sixty-five percent of patients
with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with
Wilson's disease were positive for at least one autoantibody. In the 51 subjects
with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on
165 occasions over a median of 9 months (range 5-42 months), autoantibodies to
nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver
kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and
untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in
67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had
to be suspended due to transaminase elevation in one SMA-positive, one ANA
positive but in three of four LKM-1-positive patients. Our results show that: (i)
autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii)
positivity for SMA, GPC, ANA is part of the natural course of chronic HCV
infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha
should be used cautiously in the treatment of LKM-1/HCV-positive patients.
PMID- 9649218
TI - Production of cytotoxic factor by peripheral blood mononuclear cells (PBMC) in
patients with dengue haemorrhagic fever.
AB - A unique cytokine, human cytotoxic factor (hCF), has been shown to occur in the
sera of patients with dengue fever (DF) and dengue haemorrhagic fever (DHF). The
present study was undertaken to investigate the ability of fresh PBMC of such
patients to produce hCF. The PBMC were cultured for 24 h and the culture
supernatants (CS) were analysed for the presence of hCF by cytotoxicity assay,
competitive ELISA and dot blot tests. In 90% of 246 cases CS were positive for
hCF by the three tests. CS were positive for hCF in PBMC collected from days 1-20
of illness but not at later periods. Higher cytotoxic activity was observed in CS
of days 1-4 of illness and was highest in cases of DHF grade IV and lowest in
cases of DF. Dot blot hybridization of RNA extracted from the PBMC of the
patients showed the presence of mRNA for hCF in 94% of cases. A similar number of
patients showed the presence of hCF in situ in the PBMC smears by fluorescent
antibody technique. hCF was found only in CD4+ T cells. The findings thus present
direct evidence of the production of hCF by CD4 T cells of cases of DF/DHF.
PMID- 9649219
TI - The human autoantigen La/SS-B accelerates herpes simplex virus type 1 replication
in transfected mouse 3T3 cells.
AB - Permanently transfected mouse cell lines which expressed different levels of the
human autoantigen La/SS-B were infected with different strains of herpes simplex
virus type 1, including the strains ANG, HSZP, 17syn+ and HFEM. During infection
the localization of the human La protein was followed using an anti-La MoAb,
which recognized only the human La protein but did not cross-react with either
the endogenous mouse La protein or any viral encoded protein. After infection La
protein was transported from the nucleus to the cytoplasm. The time course of
translocation was dependent on the amount of human La protein expressed in the
respective cell line. Moreover, acceleration of viral replication was dependent
on the level of expression of human La protein, suggesting that La protein is a
cellular factor that facilitates virus replication.
PMID- 9649220
TI - Circulating antibodies to the 60-kD heat shock protein (hsp) family in patients
with Helicobacter pylori infection.
AB - Whilst the mechanism by which Helicobacter pylori causes different gastroduodenal
diseases is uncertain, strains producing the cytotoxin-associated protein (CagA)
have greater pathogenicity. Hsps are immunogenic molecules induced by
inflammatory mediators. The aim of this study was to assess pathogenicity of hsp
antibodies in H. pylori-infected patients. ELISA techniques were used to assay
sera of H. pylori-positive patients with gastritis, gastric atrophy, duodenal or
gastric ulcer, and H. pylori-negative controls, for antibodies to CagA and to
human, mycobacterial, and in 20 sera, H. pylori (hspB) 60-kD hsp. IgA antibodies
to mycobacterial hsp60 in atrophy patients were elevated compared with patients
with gastritis (P < 0.05) and with H. pylori-negative controls (P < 0.0005). IgA
antibodies to human hsp60 in gastric atrophy patients were elevated compared with
H. pylori-negative controls (P < 0.05). Patients with atrophy (P < 0.0005) and
gastritis (P < 0.05) who were CagA-positive had raised titres of anti
mycobacterial hsp60 IgA antibodies compared with controls. IgA antibody levels to
hspB were positively correlated with those to mycobacterial hsp60 (mhsp60) (P <
0.05) and human hsp60 (hhsp60) (P < 0.005). IgA antibodies to hsp60 are
associated with gastroduodenal disease, particularly gastric atrophy, in H.
pylori-infected patients. Increased humoral responses to hsp60 could either
contribute to gastric atrophy or result from greater gastric mucosal damage
induced by CagA-positive strains of H. pylori.
PMID- 9649221
TI - Deoxyspergualin preferentially inhibits the growth and maturation of anti-CD40
activated surface IgD+ B lymphocytes.
AB - Deoxyspergualin (DSG), an analogue of spermidin, is a potent immunosuppressive
drug with an action quite distinct from that of cyclosporin, rapamycin, or FK506.
In this study we investigated the effect of DSG and methyldeoxyspergualin (MeDSG)
on the proliferation and differentiation of human B cells stimulated with anti
CD40 MoAb. Highly purified B cells obtained from tonsillar samples were used as
target cells. Both agents inhibited the proliferative response of anti-CD40
stimulated B cells in the absence and presence of IL-4, IL-2 or IL-10 in a dose
dependent manner. This inhibitory effect differed markedly among cell populations
based on surface IgD expression: strong inhibition of sIgD+ B cells but little
inhibition of sIgD- B cells. The drugs also suppressed the production of IgG, IgM
and IgA by unfractionated B cells, which suggests that DSG acts against post
switch (sIgD-) B cells. Although the drugs suppressed immunoglobulin synthesis by
both sIgD+ and sIgD- B cells, the effect was more marked in the sIgD+ B cells.
Analysis of the subclass of IgG secreted by sIgD+ B cells revealed a decline in
IgG1 and IgG3 in the presence of DSG. These results suggest that DSG
preferentially inhibits the growth and maturation of sIgD+ naive B cells.
PMID- 9649222
TI - Selective depletion of CD14+ CD16+ monocytes by glucocorticoid therapy.
AB - Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents
that act on many cells of the body, including monocytes. Here we show that a 5
day course of high dose GC therapy differentially affected the CD14++ and the
CD14+ CD16+ monocyte subpopulations in 10 patients treated for multiple
sclerosis. While the classical (CD14++) monocytes exhibited a substantial
increase from 495 +/- 132 to 755 +/- 337 cells/microl, the CD14+ CD16+ monocytes
responded with a pronounced decrease from 36 +/- 15 to 2 +/- 3 cells/microl (P <
0.001). In 4/10 patients the CD14+ CD16+ monocytes fell below detection limits
(<0.2 cells/microl). This observation was confirmed when the CD14+ CD16+
monocytes were identified by virtue of their low CD33 expression as these cells
decreased as well. After discontinuation of GC therapy the CD14+ CD16+ monocytes
reappeared and reached normal levels after 1 week. The profound depletion of
CD14+ CD16+ monocytes by GC as described here is a novel effect of GC action in
vivo and may contribute to GC-mediated immunosuppression. Determination of the
number of this monocyte subset may also serve to monitor the effectiveness of GC
therapy in patients requiring immunosuppressive treatment.
PMID- 9649223
TI - Identification and characterization of autoantibodies against catalase and alpha
enolase in patients with primary sclerosing cholangitis.
AB - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of
unknown aetiology. Recent studies have shown that genetic factors and both
cellular and humoral immunological abnormalities are important in the
pathogenesis of PSC. The most prominent autoantibodies in PSC are anti-neutrophil
cytoplasmic antibodies (ANCA). The autoepitopes of ANCA in PSC are not well
defined. The aim of this study was to identify corresponding ANCA autoantigens in
patients with PSC. A biochemical approach with enrichment and partial
purification of soluble neutrophil proteins, detection of autoantibodies by
Western blot and partial amino acid sequencing were used. Two new
autoantigen/autoantibody systems in patients with PSC were detected: catalase and
alpha-enolase. The presence of catalase autoantibodies in 9/15 (60%) and alpha
enolase autoantibodies in 4/15 (27%) was confirmed by ELISA and Western blot.
Furthermore, we showed immunoreactions of PSC sera with human biliary epithelial
cells, showed the reduction of fluorescence in anti-catalase absorption
experiments and observed partial co-localization of anti-catalase antibodies and
PSC sera in double-staining experiments on biliary epithelial cells. The anti
catalase antibody-positive PSC patients had a more severe course of disease with
a significantly higher alkaline phosphatase compared with the anti-catalase
negative PSC patients (P < 0.06). All ulcerative colitis control sera were anti
catalase antibody-negative. The identified antigens catalase and alpha-enolase
can partly explain the ANCA fluorescence on ethanol-fixed and formaldehyde-fixed
granulocytes in patients with PSC. Catalase is an important anti-oxidant enzyme
and prevents cell damage from highly reactive oxygen-derived free radicals.
Catalase autoantibodies might play a pathogenic role in patients with PSC. Our
findings support the hypothesis that oxidative stress is one of the pathogenic
mechanisms in patients with PSC.
PMID- 9649224
TI - VH usage and somatic hypermutation in peripheral blood B cells of patients with
rheumatoid arthritis (RA).
AB - The human antibody repertoire has been demonstrated to have a marked V-gene
dependent bias that is conserved between individuals. In RA patients, certain
heavy chain V genes (VH) have been found to be preferentially used for encoding
autoantibodies. To determine if such preferential use of VH genes in
autoantibodies is associated with a general distortion of the V gene repertoire
in RA patients, the VH composition of peripheral blood B cells was analysed among
four RA patients and four age- and sex-matched healthy controls. Usage of
individual VH genes (eight VH3 and three VH4 genes tested by hybridization with a
set of gene-specific oligonucleotide probes) was highly biased among RA patients,
but no evidence of a distortion in the bias was observed compared with healthy
controls. However, the occurrence of somatic mutations in these VH genes
(estimated by differential hybridization with motif-specific oligonucleotide
probes targeted to CDR and FR of the tested genes, and by DNA sequence analysis)
was strikingly different between patients and healthy subjects. The number of VH3
rearrangements that had accumulated somatic mutations and the number of mutations
per rearrangement were significantly elevated in three of the four RA patients. A
slight but not significant elevation in mutations among rearranged VH4 genes was
also observed in these patients. These data suggest that although usage of
individual VH genes among peripheral blood B cells is not affected by the
disease, the autoimmune process may involve a significant fraction of the B cell
compartment.
PMID- 9649225
TI - IL-10 and IL-4 co-operate to normalize in vitro IgA production in IgA-deficient
(IgAD) patients.
AB - In the present study we evaluated in vitro immunoglobulin production from IgAD
individuals and healthy controls. Peripheral blood mononuclear cells (PBMC) from
IgAD and controls were cultured with anti-CD40 MoAb presented on a CDw32
transfected fibroblast cell line (CD40 system) in the presence of IL-10, IL-2, IL
4, transforming growth factor-beta (TGF-beta) alone as well as of IL-10 in
combination with each of the other three cytokines. Only IL-10 added alone
induced significant changes in baseline immunoglobulin production; marked
increases in median supernatant levels of all three isotypes were observed in
both groups. The most striking finding of this study was the synergizing effect
of IL-4 on IgA production in the IgAD group when added with IL-10; median IgA
supernatant level increased to a value superimposable on that found in the normal
controls which remained about the same as when stimulated with IL-10 alone. The
synergic effect of IL-4 and IL-10 was specific to the IgA isotype.
PMID- 9649226
TI - Detection of Fcgamma receptors on human endothelial cells stimulated with
cytokines tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
gamma).
AB - This investigation was conducted to detect Fcgamma receptors (FcgammaR) on
cytokine-stimulated human endothelial cells (EC) by measuring anti-FcgammaR MoAb
binding with an ELISA. TNF-alpha and IFN-gamma significantly increased the
expression of FcgammaR type II (FcgammaRII) and type III (FcgammaRIII) on aortic
EC. Simultaneous treatment with both cytokines had a synergistic effect and
pretreatment of EC with IFN-gamma augmented the effect of TNF-alpha. The greatest
effect was the increase (up to four-to-six-fold) in expression of FcgammaRII
found by the simultaneous treatment of aortic EC with both cytokines. The
receptors were expressed on the cell surface and showed receptor capping after
incubation at 37 degrees C. This study showed that the inflammatory cytokines TNF
alpha and IFN-gamma enhanced low-affinity FcgammaR expression on human EC in
vitro. The expression of FcgammaR may contribute to the specific localization of
circulating immune complexes on blood vessels in areas of vasculitis.
PMID- 9649227
TI - T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA)
antigens are present in patients with ANCA-associated systemic vasculitis and
persist during disease remission.
AB - ANCA with specificity for myeloperoxidase (MPO) and proteinase 3 (PR3) are
present in patients with systemic vasculitis. The aim of this work was to
determine whether such patients have T cell responses to these antigens and
whether these responses are related to disease activity. Peripheral blood
lymphocytes from 45 patients and 19 controls were cultured with ANCA antigens and
proliferation measured. The antigens used were heat-inactivated (HI) MPO, HI PR3,
native (non-HI) PR3, HI whole alpha-granules, and 25 overlapping peptides
covering the entire PR3 sequence. Significant responses to both whole PR3
preparations were seen from patient and control groups, and to the alpha-granules
from the patient group. Patients responded at all stages of disease: active,
remitting, treated or untreated. Only two patients responded significantly to
MPO. Responses were significantly higher with the patient group than the control
group to all four whole ANCA antigens. Responses to those PR3 peptides containing
epitopes known to be recognized by ANCA were detected from one patient. Thus,
these studies demonstrate that T cells from vasculitis patients can proliferate
to PR3 and occasionally to associated ANCA antigens. Further, responses may
persist even after disease remission has been achieved.
PMID- 9649228
TI - Biologic foundation of the therapy for advanced germ cell tumors.
AB - An understanding of the elements that have contributed to the remarkable cure
rate in patients with germ cell cancers is a useful exercise for clinicians. The
prevailing view is that the introduction of chemotherapy was largely responsible
for this remarkable success. Although chemotherapy is clearly the required
ingredient, there are other important contributing factors that were essential
for the high cure rate. These contributing elements include the understanding of
the biology of the cancer and the availability markers. The understanding of the
clinical biology and ability to assay persistent minimal cancer led to the
appropriate integration of systemic and local therapies. The treatment of germ
cell cancers is the paradigm of multidisciplinary therapy of cancer because it
accommodates many variables into the clinical decision-making process.
PMID- 9649229
TI - Integration of surgery and systemic therapy: results and principles of
integration.
AB - Eight hundred seventy patients with metastatic nonseminomatous germ cell cancer
underwent postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for
resection of residual disease. Several risk factors for relapse and survival were
identified as highly significant (P = .00001), namely, presence of residual
cancer in the specimen before salvage chemotherapy programs, tumor marker
elevation, need for "re-do" PC-RPLND, or unresectability. Although more than half
of the entire group (52.5%) had one or more of these risk factors, 67.5% are long
term survivors following PC-RPLND. The remaining 47.5% were referred after
primary chemotherapy, without risk factors. Only 9.8% relapsed and 95.5%
survived.
PMID- 9649230
TI - Testicular tumors: clinically relevant histological findings.
AB - Testicular germ cell neoplasms affect young men in the prime of life. Although
the overwhelming majority are malignant, they are curable. In addition to the
stage of the disease and the presence of serum markers, there are important
pathological changes that have clinical significance. These include (1) the cell
type, (2) the amount of the component, and (3) the presence or absence of
vascular invasion. Pure embryonal carcinoma or embryonal carcinoma in excess of
80% in a mixed tumor and vascular/lymphatic invasion are high-risk factors as
they are predictors of relapse. These factors should be recognized by the
pathologist and should be taken into account by the oncologist when selecting the
management of a patient with a germ cell tumor of the testis.
PMID- 9649231
TI - Germ cell tumors: staging, prognosis, and outcome.
AB - Germ cell tumors (GCT) remain the model for solid tumor therapy. Until 1997, GCT
staging was based on individual institution systems, which limited comparison of
data and collaboration between GCT groups. GCT staging is based on four basic
criteria: disease site of origin, histology, secretion of serum tumor markers
(STM), and bulk of disease. Within most staging systems developed by
investigators, clinical stage I disease is confined to the testis based on
radiographic imaging and STM or pathological stage I based on lack of
histological disease at retroperitoneal lymphadenectomy. Stages II and III are
considered to be disease outside the testis categorized by lymphatic spread to
the retroperitoneal lymph nodes or hematological spread to lungs and visceral
organs, respectively. The major staging systems previously used include the
Indiana University Staging System; Modified Samuels' Classification (M.D.
Anderson Cancer Center); Memorial Sloan Kettering Cancer Center Mathematical
Model; and the Tumor, Nodal, Metastases (TNM) Staging System (American Joint
Committee on Cancer). The most recent evolution in staging systems is the 1997
International Germ Cell Consensus Classification, which is based on prognosis and
outcomes. This system allows for comparison of data and collaboration between
Germ Cell Tumor Groups.
PMID- 9649232
TI - Dose intensity: its limitation and the M. D. Anderson Cancer Center's view of its
application.
AB - Therapy for germ cell tumors has been viewed as a model of successful treatment
development in solid tumors. Despite this, treatment remains unsatisfactory in
patients with poor risk or high volume at initial presentation. Present
strategies under investigation include the use of dose intensification through
the shortening of treatment intervals and the dose escalation of agents with a
presumed dose-response relationship in the presence or absence of bone marrow
transplant or stem cell support.
PMID- 9649233
TI - Heat-related mortality--United States, 1997.
AB - Environmental heat exposure can cause illness, injury, and death. This report
describes four heat-related deaths that occurred in the United States during 1997
and summarizes risk factors for and reviews measures to prevent heat-related
illness, injury, and death.
PMID- 9649234
TI - Statewide surveillance for ehrlichiosis--Connecticut and New York, 1994-1997.
AB - In the United States, human monocytic ehrlichiosis (HME) and human granulocytic
ehrlichiosis (HGE) represent two clinically indistinguishable yet
epidemiologically and etiologically distinct diseases caused by Ehrlichia
chaffeensis and a bacterium similar or identical to E. equi, respectively.
Infection with these emerging tickborne pathogens results in acute, influenza
like illnesses with fever, headache, malaise, and frequently leukopenia and/or
thrombocytopenia. Connecticut and New York have initiated statewide laboratory
based surveillance to determine the magnitude and geographic extent of
ehrlichiosis. This report summarizes results from the first 3 years of
surveillance, which showed that rates of ehrlichiosis were similar in counties in
both states where the disease occurs, and highest age-specific rates occurred
among persons aged >40 years.
PMID- 9649235
TI - Sun-protection behaviors used by adults for their children--United States, 1997.
AB - In the United States, the high incidence of skin cancer--including basal cell
carcinoma, squamous cell carcinoma, and melanoma-has been attributed primarily to
sun exposure. To reduce exposures to the sun's harmful ultraviolet (UV) rays, the
American Academy of Dermatology (AAD), the American Cancer Society, and other
organizations have recommended sun-protection practices such as wearing
protective clothing, avoiding sun exposure during the midday hours (when the
sun's rays are the strongest), and using sunscreen. Such practices are especially
important for infants and children because sun exposure during the early years of
life appears to increase the risk for melanoma, the most serious form of skin
cancer. To characterize sun-protection practices among children, AAD conducted a
survey of parents with children aged < or =12 years during June-July 1997. This
report summarizes the results of the survey, which indicate that three fourths of
adults had their children use one or more measures to reduce exposure to UV rays.
PMID- 9649236
TI - Multistate outbreak of hemolysis in hemodialysis patients--Nebraska and Maryland,
1998.
AB - From May 13 through May 23, 1998, a total of 30 patients in three states
developed hemolysis with or without chest pains, shortness of breath, nausea, or
abdominal pain while undergoing hemodialysis (HD). Two patients died. This report
summarizes the preliminary findings of investigations in Nebraska and Maryland
and implicated lot number 04015309 of Cobe Centrysystem 3 Blood Tubing sets
(Gambro Healthcare, Lakewood, Colorado) as the cause of these reactions.
PMID- 9649237
TI - Studies on gender differences in beta-adrenergic receptors in rabbit bladder.
PMID- 9649238
TI - Positron emission tomography in urological oncology.
AB - PURPOSE: We provide scientists and clinicians with an introduction to the basic
principles and methods of positron emission tomography (PET) and summarize the
recent research and clinical applications of PET in the urological field.
Specifically, we introduce PET so that the reader can understand and objectively
review current and future articles that involve this imaging technology.
MATERIALS AND METHODS: The recent applications of PET in urology in the published
literature were searched and reviewed. RESULTS: In prostate carcinoma preliminary
studies using radiotracer 18-fluoro-2-deoxyglucose (FDG) demonstrated that PET
cannot reliably differentiate between primary prostate cancer and benign
prostatic hyperplasia, and that PET is not as sensitive as bone scintigraphy for
the detection of osseous metastases. However, PET may have a role in the
detection of lymph node metastases in patients with prostate specific antigen
relapse after primary local therapy. In renal cell carcinoma recent studies have
shown the ability of FDG PET to detect primary and metastatic lesions and to
monitor response to therapy. In the staging of testicular cancer FDG PET has been
used to differentiate viable carcinoma from benign teratomas and/or fibrotic or
necrotic changes. CONCLUSIONS: Current developments in PET technology that
accurately stage the extent of tumor before surgery as well as monitor
effectiveness or ineffectiveness of new or current therapies may make PET a
valuable tool in research and in the management of urological diseases.
PMID- 9649239
TI - Long-term outcome in patients with pTxN+ adenocarcinoma of prostate treated with
radical prostatectomy and early androgen ablation.
AB - PURPOSE: We assessed retrospectively the outcome after bilateral pelvic
lymphadenectomy and radical prostatectomy for pathological pTxN+ adenocarcinoma
of the prostate when treated with or without adjuvant androgen ablation therapy.
MATERIALS AND METHODS: A total of 790 men treated with radical prostatectomy for
prostatic adenocarcinoma were found to have pTxN+ disease and treated further
with or without androgen ablation therapy. Mean patient age was 64 years (range
40 to 79). Mean followup was 6.5 years, (range up to 25). Clinical stages were T2
or less in 60% of the cases, T3 in 38% and N+ in 2%. Gleason scores were 6 or
less in 31% and 7 or greater in 69%. Deoxyribonucleic acid ploidy was diploid in
43%, tetraploid in 39% and aneuploid in 18%. Of the patients 96 (12%) received no
androgen ablation therapy, with the remainder getting androgen ablation therapy
within 90 days of radical prostatectomy. RESULTS: Of the patients 186 (24%) died,
with 109 (14%) dying of prostatic anedocarcinoma. Overall (and cause specific)
survival probabilities at 5, 10 and 15 years were 87 (91), 69 (79) and 39% (60%),
respectively. Patients with diploid tumors had better cause specific survival
than those with nondiploid tumors (p = 0.009). Patients with diploid tumors were
less likely to have progression biochemically, locally or systemically than those
with nondiploid tumors (p = 0.038). Androgen ablation therapy had no effect on
cause specific survival in nondiploid patients. Diploid patients treated with
androgen ablation therapy for up to 10 years had no improvement in disease
specific survival compared to those with no androgen ablation therapy. However,
cancer death was significantly reduced after 10 years (p <0.002). The local
control rate of pTxN+ cases that receive radical prostatectomy and androgen
ablation therapy at 15 years is virtually identical to that of stage pT2c cases
at our institution (79 +/- 3.0 versus 80% +/- 3.5%, respectively). There were no
deaths secondary to radical prostatectomy, and complications were within the
experience of that seen in patients with localized disease. CONCLUSIONS: Radical
prostatectomy with androgen ablation therapy is a viable option for patients with
pTxN+ disease, particularly in view of excellent local control rates and low
morbidity. Patients with diploid tumors have a more favorable outcome than those
with nondiploid tumors when treated with androgen ablation therapy.
PMID- 9649240
TI - Renal colic during pregnancy: a case for conservative treatment.
AB - PURPOSE: We defined the merits of early evaluation and conservative treatment of
pregnant patients admitted with renal colic. MATERIALS AND METHODS: We
retrospectively evaluated 72 pregnancies in 70 patients who were hospitalized
with the diagnosis of renal colic between 1984 and 1995. Urinalysis was performed
in every case. Ultrasound was the primary diagnostic test in 65 patients. The
patients were followed for 2 weeks to 3 months after delivery (mean 21 days).
RESULTS: Mean patient age at presentation was 27.4 years. The majority of
patients were multiparous (47 of 70) and presented in the third trimester (44 of
70). Microscopic urinalysis was not helpful in identifying stone disease in
pregnant patients. The sensitivity of ultrasound for the diagnosis of renal
calculi was 95.2%. Watchful conservative nonsurgical treatment resulted in
spontaneous passage of stones in 64.3% of cases. Of the 19 pregnancies in which
intervention was necessary cystoscopy and Double-J* silicone stent placement were
done in 15, and ureteroscopy and stone basketing were done in 4. Two patients,
who presented with pyelonephritis and premature ruptured membranes had fetal
loss. Long-term antibiotic prophylaxis was maintained in all stented and
bacteriuric patients. CONCLUSIONS: Renal colic in pregnant patients can be
complicated by pyelonephritis and premature labor, especially if misdiagnosed or
inadequately treated. Ultrasound is a safe and sensitive diagnostic test.
Approximately two-thirds of renal calculi will pass spontaneously. For those who
require intervention, placement of a Double-J stent is a safe and effective
option.
PMID- 9649241
TI - Predictors of outcome in emphysematous pyelonephritis.
AB - PURPOSE: We identified and quantified prognostic factors for emphysematous
pyelonephritis. MATERIALS AND METHODS: The clinical information, laboratory data
and radiological findings from 38 patients with emphysematous pyelonephritis were
retrospectively analyzed. RESULTS: There were no significant differences between
the nonsurvivor and survivor groups with respect to age, gender, diabetes
mellitus history, presence of bacteremia, identity of infecting organisms, blood
glucose level, leukocyte count, urinary white blood count, presence or absence of
urinary tract obstruction or urolithiasis, and modes of treatment. There were
significant differences between the nonsurvivor and survivor groups, however,
with respect to platelet count (84,300 +/- 119,500 versus 220,400 +/-
161,800/mm.3, p = 0.001), serum creatinine level (3.61 +/- 1.25 versus 2.19 +/-
1.32 mg./dl., p = 0.003) and urinary red blood counts (56.47 +/- 41.86 versus
27.65 +/- 36.14, p = 0.028). Patients with radiological type I emphysematous
pyelonephritis were significantly more likely to die than those with type II (69
versus 18%, p = 0.002). CONCLUSIONS: Serum creatinine level is the most reliable
predictor of outcome in patients with emphysematous pyelonephritis. By
calculating likelihood ratios, patients with creatinine levels greater than 1.4
mg./dl. and platelet counts 60,000/mm.3 or less were at high risk. The posttest
probability of death increased from 69 and 18% to 92 and 53% for type I and II
emphysematous pyelonephritis, respectively. Patients with creatinine levels 1.4
mg./dl. or less and platelet counts greater than 60,000/mm.3 were at much lower
risk. Posttest mortality risk in these patients dropped from 69 and 18% to 27 and
4% for type I and II emphysematous pyelonephritis, respectively.
PMID- 9649242
TI - Current indications for open stone surgery in the treatment of renal and ureteral
calculi.
AB - PURPOSE: The development and advances in extracorporeal shock wave lithotripsy
and endourological procedures have greatly diminished the need for open surgery
in the treatment of renal and ureteral stones. We reviewed our experience with
open stone surgery to determine the current indications and efficacy of this
treatment modality. MATERIALS AND METHODS: Hospital and office charts, operative
notes and records, and pertinent radiographic studies of all patients undergoing
open stone surgery from January 1991 through December 1995 at 3 university
affiliated hospitals were reviewed. Patient characteristics, stone burden,
indications, surgical factors and outcomes were reviewed for each patient.
RESULTS: Of 780 procedures performed for stone removal, 42 were open surgical
procedures (5.4%) including pyelolithotomy in 15 (extended pyelolithotomy or
pyelonephrolithotomy in 7), anatrophic nephrolithotomy in 14, ureterolithotomy in
7 and radial nephrolithotomy in 6. There were 24 men and 18 women ranging in age
from 1 to 90 years (mean age 51.5). The most common indications for open surgery
were complex stone burden (55%); failure of extracorporeal shock wave lithotripsy
or endourological treatment (29%); anatomic abnormalities such as ureteropelvic
junction obstruction, infundibular stenosis and/or renal caliceal diverticulum
(24%); morbid obesity (10%) and co-morbid medical disease (7%). Mean estimated
blood loss was 428 cc. Average hospital stay was 6.4 days. The stone-free rate
after surgery was 93%. Five patients had minor postoperative complications that
resolved with appropriate therapy. CONCLUSIONS: While most patients with renal
and ureteral stones can be treated with less invasive techniques, open stone
surgery continues to represent a reasonable alternative for a small segment of
the urinary stone population.
PMID- 9649243
TI - Relationship between glutathione S-transferase M1 deficiency and urothelial
cancer in dye workers exposed to aromatic amines.
AB - PURPOSE: It is speculated that the susceptibility to urothelial cancer in dye
workers who are exposed to aromatic amines is affected not only by occupational
environmental factors but by host specific factors. We evaluated the interaction
between glutathione S-transferase M1 gene deficiency and the occupational
environmental factors associated with urothelial cancer. MATERIALS AND METHODS:
The study included 137 workers who had prior exposure to dyestuff intermediates,
of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase
M1 gene polymorphism was investigated using polymerase chain reaction. The
relationship between the glutathione S-transferase M1 0/0 gene and occupational
environmental factors in the onset of urothelial cancer was examined by
multivariate analysis. RESULTS: The prevalence of glutathione S-transferase M1
gene deficiency did not differ significantly between the urothelial cancer (21
cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that
29.6% of the urothelial cancers in these dye workers was attributable to the
glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models
showed low predictive ability for urothelial cancer due to glutathione S
transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence
interval [CI] 0.904 to 5.652). A history of working in small factories (p =
0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p
= 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted
cancer. CONCLUSIONS: We demonstrated a strong trend using the multiple logistic
analysis of the contribution of glutathione S-transferase M1 gene polymorphism
and occupational environmental factors. Therefore, the glutathione S-transferase
M1 enzyme might have an important role in the detoxification of aromatic amine
derived carcinogens. Occupational environmental factors, however, might
contribute more than a glutathione S-transferase M1 gene deficiency to the
occurrence of urothelial cancer among individuals exposed to aromatic amines,
because of the extremely potent carcinogenicity of some occupational
environmental factors.
PMID- 9649244
TI - Use of Lewis X antigen and deoxyribonucleic acid image cytometry to increase
sensitivity of urinary cytology in transitional cell carcinoma of the bladder.
AB - PURPOSE: To improve sensitivity and specificity of urinary cytology for bladder
cancer cell detection we used deoxyribonucleic acid (DNA) image cytometry and the
monoclonal anti-Lewis X antibody P12. MATERIALS AND METHODS: Spontaneously voided
urine and additional barbotage bladder washings of 25 patients with transitional
cell carcinomas and 25 patients with benign diseases of the bladder were analyzed
by conventional cytology, immunocytology and DNA image cytometry. The DNA content
was determined in specimens stained with Feulgen according to the European
Society for Analytical Cellular Pathology consensus report on standardization of
DNA image cytometry. For the immunocytological examination we used the avidin
biotin-complex immunoperoxidase method with the monoclonal antibody P12 directed
against the Lewis X determinant. RESULTS: The cytological examination revealed a
sensitivity of 72% and a specificity of 100%. By using DNA image cytometry with
Kolmogoroff-Smirnow test sensitivity increased up to 84% with a specificity of
100%. The immunocytological examination with Lewis X showed a sensitivity of 84%
and a specificity of 80%. CONCLUSIONS: Combining cytology and DNA cytometry the
overall sensitivity increased to 92% and with the additional application of
immunocytology for Lewis X antigen sensitivity it increased to 96% but was
accompanied by a decrease in specificity to 80%. DNA image cytometry and Lewis X
antigen detection are not suitable for screening but suspicious urothelial cells
in urinary cytology specimens can be evaluated specifically by DNA measurements.
In the future it needs to be clarified whether DNA image cytometry in combination
with Lewis X antigen detection can help to signal relapse and progression of
transitional cell carcinoma of the bladder.
PMID- 9649245
TI - Immunostaining of Lewis X in cells from voided urine, cytopathology and
ultrasound for noninvasive detection of bladder tumors.
AB - PURPOSE: We examined the use of immunostaining of the Lewis X antigen in
exfoliated cells from voided urine samples, cytopathology and bladder ultrasound
for noninvasive detection of bladder tumors as a potential substitute for
cystoscopy. MATERIALS AND METHODS: A total of 260 patients were included, of whom
80 were evaluated because of irritative symptoms or hematuria and 180 were
examined during followup visits after resection of bladder tumors. Voided urine
samples were obtained from each patient for immunocytology and cytopathology.
Bladder ultrasound and cystoscopy were performed. Biopsies were obtained whenever
a bladder tumor was seen or if carcinoma in situ was suspected. Indirect
immunoperoxidase staining was done on cytocentrifuge slides, using the P12
monoclonal antibody against the Lewis X antigen. RESULTS: Cystoscopy and biopsies
revealed bladder tumors in 84 patients. Immunocytology of 1 urine sample resulted
in a sensitivity of 79.8% and a specificity of 86.4%. The diagnosis of primary
carcinoma in situ by immunocytology was correct in 100% of the cases. The
examination of 2 consecutive urine samples detected 95.1% of the tumors. False
negative results occurred in a few cases with small, superficial, low grade
tumors. Cytopathology and bladder ultrasound resulted in a sensitivity of 47.6
and 66.7%, and a specificity of 97.7 and 97.2%, respectively. The results of
immunocytology of 2 urine samples were equivalent to the combination of
immunocytology of a single urine sample, cytology and ultrasound. CONCLUSIONS:
Immunostaining of the Lewis X antigen is significantly more sensitive than
cytopathology for the detection of low grade as well as high grade tumor cells in
voided urine. Immunocytological evaluation of 2 consecutive voided urine
specimens for the Lewis X antigen is the most sensitive method currently
available for noninvasive detection of transitional cell tumors. This assay may
replace cystoscopy for detection of bladder cancer.
PMID- 9649246
TI - Evaluation of NMP22 in the detection of transitional cell carcinoma of the
bladder.
AB - PURPOSE: Urinary nuclear matrix protein (NMP22) was evaluated for detection of
new and recurrent bladder tumors in patients with a history of transitional cell
carcinoma. Our objective was to determine sensitivity and specificity of this
marker for tumors of various stages and grades, as well as its use as an adjunct
to or substitute for urinary cytology. MATERIALS AND METHODS: A total of 231
patients with a history of transitional cell carcinoma provided 288 voided urine
samples before cystoscopic examination at 1 of 3 institutions (53 patients were
reevaluated at least once). Urine samples were assayed for NMP22 using the NMP22
Test Kit. Select patients underwent biopsy with appropriate additional therapy.
Voided urinary cytology was obtained in 200 cases. End points for determination
of the absence and presence of tumor were negative cystoscopy and positive
biopsy, respectively. A receiver operating characteristics curve was constructed
to determine the optimal NMP22 threshold for detection of transitional cell
carcinoma. For positive biopsies NMP22 values were also correlated with tumor
stage and grade. Comparison to cytology was limited to patients with complete
data. RESULTS: There were 208 negative cystoscopies (158 with cytology) and 66
positive cystoscopies with biopsy (42 with cytology). Of the cases 14 were
eliminated from statistical analysis due to incomplete data. Receiver operating
characteristics curve interpretation determined that 6.4 units per ml. was an
optimal reference value for detection of transitional cell carcinoma in this
patient group. Sensitivity and specificity for all pathological groupings was 68
and 80%, respectively. When compared to cytology the sensitivities of NMP22 and
cytology were 67 versus 31 or 40% (depending on the definition of positive
cytology). CONCLUSIONS: NMP22 values represented significant improvement over
urinary cytology for detection of transitional cell carcinoma. The sensitivity of
NMP22 for detection of transitional cell carcinoma in bladder cancer patients was
as much as twice that of cytology when a reference value of 6.4 units per ml. was
used. NMP22 analysis was less costly than cytology and operator independent.
While NMP22 has previously been shown to be a strong predictor of recurrence
after tumor resection, it is an effective and sensitive screening test for
detecting tumors in patients with transitional cell carcinoma.
PMID- 9649247
TI - Is the role of cystoscopy in the detection of bladder cancer really declining?
PMID- 9649248
TI - Early clinical experience with 5-aminolevulinic acid for the photodynamic therapy
of upper tract urothelial tumors.
AB - PURPOSE: Photodynamic therapy is effective in the treatment of superficial
urothelial cancer of the bladder. We report our experience with photodynamic
therapy for the treatment of upper urinary tract transitional cell carcinoma.
MATERIALS AND METHODS: Photodynamic therapy after oral administration of 5
aminolevulinic acid was performed in 4 patients with widespread superficial
papillary tumors of the upper urinary tract. RESULTS: Complete remission occurred
in 2 patients who remained free of local recurrence at 7 and 17 months of
followup. In the other 2 patients residual tiny papillary tumors were found in
the distal ureter after photodynamic therapy. These tumors were coagulated with
neodymium:YAG laser irradiation. Both patients are disease-free at 24-month
followup. CONCLUSIONS: Photodynamic therapy with 5-aminolevulinic acid is a
minimally invasive approach for organ preserving treatment of multifocal
superficial transitional cell carcinoma of the upper urinary tract.
PMID- 9649249
TI - Detection of Mycoplasma genitalium in patients with urethritis.
AB - PURPOSE: We attempted to detect Mycoplasma genitalium in urethral swab specimens
by a polymerase chain reaction based assay to determine the prevalence of M.
genitalium in patients with urethritis. MATERIALS AND METHODS: We examined a
total of 171 Japanese men who presented to our hospital from February 1995
through January 1997. Of these men 150 had symptoms and signs compatible with
acute urethritis and 21 had no symptoms or signs of urethritis. Urethral swab
specimens were used to culture Neisseria gonorrhoeae, to detect Chlamydia
trachomatis by an enzyme immunoassay and to detect M. genitalium by a polymerase
chain reaction based assay. RESULTS: Gonococcal urethritis was diagnosed in 74
symptomatic men, and nongonococcal urethritis was diagnosed in 76 symptomatic
men. Of the 74 cases of gonococcal urethritis 3 (4.1%) were positive for M.
genitalium, and 14 (18.9%) were positive for C. trachomatis. Of the 76 cases of
nongonococcal urethritis 10 (13.2%) were positive for M. genitalium, and 42
(55.2%) were positive for C. trachomatis. While only 1 of the 42 cases with
chlamydial nongonococcal urethritis (2.4%) was positive for M. genitalium, 9 of
the 34 chlamydia negative nongonococcal urethritis cases (26.5%) were positive
for the mycoplasma. In contrast, all 21 cases men were negative for N.
gonorrhoeae, M. genitalium, and C. trachomatis. CONCLUSIONS: The prevalences of
M. genitalium in patients with gonococcal urethritis and nongonococcal urethritis
who attended our clinic were 4.1 and 13.2%, respectively. M. genitalium was
detected significantly more often in men with nongonococcal urethritis than in
asymptomatic men. In addition, its prevalence in men with chlamydia negative
nongonococcal urethritis (26.5%) was significantly greater than in those with
chlamydia positive nongonococcal urethritis (2.4%). These findings suggest that
M. genitalium may be associated with the development of nongonococcal urethritis
independent of C. trachomatis.
PMID- 9649250
TI - Detection of urethral diverticula in women: comparison of a high resolution fast
spin echo technique with double balloon urethrography.
AB - PURPOSE: We compared a rapid high resolution magnetic resonance imaging (MRI)
technique to contrast urethrography for the detection of urethral diverticula in
women. MATERIALS AND METHODS: During a 19-month interval 13 patients with
clinically suspected urethral diverticula were evaluated with MRI and contrast
urethrography. All patients were referred by a urologist, and had clinical signs
and symptoms suggesting the presence of a urethral diverticulum. Double balloon
urethrography was performed in 12 patients and voiding cystourethrography was
done in 1. MRI was performed using a fast spin echo T2-weighted pulse sequence
and a dedicated pelvic multicoil. Following a sagittal localizer sequence 3 mm.
thick axial sections were obtained from the bladder base through the entire
urethra. Total imaging time was 15 minutes. RESULTS: In 7 patients MRI and
urethrography were negative for urethral diverticula, and in 3 cystourethroscopy
was negative. In 1 patient MRI revealed a vaginal inclusion cyst confirmed by
surgery. Three patients had no other studies or procedures performed. In 6
patients MRI was positive for urethral diverticula, including 4 in whom the
diverticulum was confirmed at surgery, 1 who declined surgery and 1 who was lost
to followup. Of the 4 patients (75%) with a surgically confirmed diverticulum
double balloon urethrogram was negative in 3. CONCLUSIONS: MRI is a valuable
noninvasive technique for determining the presence of urethral diverticula as
well as detecting other abnormalities. In our study MRI had a higher sensitivity
for detecting diverticula and a much higher negative predictive rate.
PMID- 9649251
TI - Periurethral fat injection in the treatment of recurrent genuine stress
incontinence.
AB - PURPOSE: We evaluated the efficacy, safety and mechanism of periurethral fat
injection in the treatment of recurrent genuine stress incontinence. MATERIALS
AND METHODS: Periurethral fat injections were performed in 26 patients for the
treatment of recurrent genuine stress incontinence. A complete urogynecological
study, including a 1-hour pad test, urodynamic studies and chain
urethrocystography were done in each case and were repeated at least 3 months
after operation. Each patient was followed for at least 12 months. RESULTS: Of 26
patients 13 (50%) were dry after operation and 4 (15.4%) showed improvement and
were satisfied with the results of the operation, giving a total success rate of
65.4%. There were 6 cases of immediate postoperative minor complications (23%).
Average volume of injected fat was 14.8 +/- 4.8 cc, which did not affect the
success rate. Preoperative and postoperative chain urethrocystographic values for
bladder neck descent in reference to the pubosacral tip line showed no
statistical difference between successfully and unsuccessfully treated groups.
Urodynamic studies in all cases showed no differences relating to operation.
However, minimal urethral resistance increased from 0.122 +/- 0.061 to 0.205 +/-
0.134 (p = 0.023) in the treatment success group. This change was not
demonstrated in the treatment failure group. CONCLUSIONS: Periurethral fat
injection for the treatment of recurrent genuine stress incontinence is a simple
technique that works by the increment of urethral resistance. It has an
acceptable success rate without financial outlay for the injected material.
PMID- 9649252
TI - Intralesional sclerotherapy in the management of hemangiomas of the glans penis.
AB - PURPOSE: We studied the role of sclerotherapy in the management of glans penis
hemangiomas. MATERIALS AND METHODS: Four patients with hemangiomas of the glans
penis were treated on an outpatient basis with intralesional injections of 30%
hypertonic saline. RESULTS: In all 4 patients the lesions regressed and all were
satisfied with the outcome. CONCLUSIONS: Intralesional sclerotherapy is a cost
effective modality for the treatment of glans penis hemangiomas, especially in
developing countries and at peripheral hospitals where expensive laser equipment
may not be available.
PMID- 9649253
TI - Burns to the genitalia and the perineum.
AB - PURPOSE: We conducted a study to determine the treatment of perineal and genital
burns, the results of therapy and the complications of such burns. MATERIALS AND
METHODS: A review of the records of 4,216 patients treated between 1981 and 1995
at the Burn Center of the Academic Surgical Center Stuivenberg, revealed 87 male
and 30 female patients, 6 months to 86 years old who had associated burns to the
perineum or genitalia. Mean burn size was 21% of the total body surface area.
Causes of burn injury were scald in 55% of the cases, flame in 24%, chemical in
16% and others in 4%. RESULTS: There were 16 deaths in this group (13.6%) but
none was related to the perineal or genital burns. Of the 101 survivors 41%
required Foley catheters but the catheters were indwelling during resuscitation
only (range 1 to 99 days). Perineal and genital burns were treated by topical
antimicrobials. Only 10 patients (9.9%) required split-thickness skin grafts. As
late complication 2 patients had scar formation of the penile shaft, which was
treated with multiple Z-plasties, and of the prepuce, which was treated by
circumcision, respectively. In 1 patient, who presented with erectile dysfunction
diagnostic evaluation was negative. CONCLUSIONS: Conservative management of
perineal and genital burns is recommended.
PMID- 9649254
TI - Management of the buried penis in adults.
AB - PURPOSE: Buried penis, most commonly seen in children, is particularly
debilitating in adults, resulting in the inability to void standing and it
affects vaginal penetration. The pathophysiology, including scar contracture of
the distal soft tissue and skin envelope with concurrent descent of the abdominal
fat pad, represents a surgical challenge. We developed a management algorithm to
evaluate and treat adults with buried penis. MATERIALS AND METHODS: From January
1, 1994 to May 1, 1996, 7 patients 23 to 66 years old presented with buried
penis. Diabetes mellitus, a common co-morbid condition, was present in 5
patients, and 5 of 7 were morbidly obese. RESULTS: Surgical correction was
performed in 5 patients with excellent results in 3. Resection of scar
contracture was sufficient to provide adequate length and none required release
of the suspensory ligament. Panniculectomy was performed in 1 patient. One man
requiring a graft to achieve adequate penile coverage required reoperation. This
patient had undergone a previous attempted repair with extensive contracture. All
patients regained potency postoperatively. CONCLUSIONS: With appropriate planning
and adherence to basic reconstructive surgical principles, correction of the
buried penis can yield a high success rate.
PMID- 9649255
TI - Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with
premature ejaculation: a double-blind, placebo controlled study.
AB - PURPOSE: We compared the efficacy and safety of fluoxetine, sertraline,
clomipramine and placebo for the oral pharmacotherapy of premature ejaculation.
MATERIALS AND METHODS: The study included 36 men (mean age 44 years) who had
intravaginal ejaculation latency of less than 2 minutes. Patients took each of 3
drugs and the placebo consecutively during a 4-week period per each agent.
Efficacy and side effects data were obtained by a self-reported patient
questionnaire that rated intravaginal ejaculation latency, sexual satisfaction of
patient and partner, and possible side effects. RESULTS: After 4 weeks of
treatment with placebo, fluoxetine, sertraline and clomipramine the mean
intravaginal ejaculation latency time was significantly increased from 46 seconds
to 2.27 minutes, 2.30 minutes, 4.27 minutes and 5.75 minutes, respectively (all p
<0.01). However, treatment with clomipramine or sertraline caused a greater
increase in mean intravaginal ejaculation latency time than fluoxetine or placebo
(p <0.01). Patient sexual satisfaction rate after treatment with clomipramine was
significantly higher (p <0.05) than with sertraline, fluoxetine or placebo.
Partner sexual satisfaction rate was also higher with clomipramine than with
sertraline or fluoxetine but no statistical difference was found. The incidence
of side effects with clomipramine was significantly higher (p <0.05) compared to
that of fluoxetine, sertraline and placebo, while no significant difference among
sertraline, fluoxetine and placebo was noted. CONCLUSIONS: In men with premature
ejaculation clomipramine was the most useful drug in terms of efficacy. Treatment
with sertraline was nearly as effective and had a lower incidence of side
effects.
PMID- 9649256
TI - Cavernous arterial and arteriolar circulation in patients with erectile
dysfunction: a power Doppler study.
AB - PURPOSE: We assessed the morphodynamic features of cavernous arteries and
helicine arterioles by power Doppler sonography in vasculogenic and
nonvasculogenic impotent men. MATERIALS AND METHODS: A total of 40 impotent
patients with and without definite vascular risk factors were studied by penile
power Doppler sonography. The test was performed during penile flaccidity, after
intracavernous injection of 20 mcg. alprostadil and after subsequent genital and
audiovisual sexual stimulation. A second injection and stimulation were given if
the erectile response observed after the initial injection was less than the
maximum erection seen during sexual activity. Morphodynamic parameters evaluated
by power Doppler imaging included vessel course, shape, wall thickness and
pulsatility, peak systolic velocity, end diastolic velocity, acceleration time
and resistance index. RESULTS: In the nonvasculogenic group all patients who
achieved rigid erection showed normal cavernosal artery and helicine arteriole
inflow. In these cases the arteriolar picture was characterized by the presence
of 3 orders of distal ramifications originating from the cavernous arteries with
an acute angle, systolic diastolic flow during penile tumescence and systolic
flow alone at full rigidity. In the vasculogenic group patients with normal
cavernous artery inflow showed an arteriolar tree that was pathological in 50%
and was characterized by a reduced number of ramifications originating
perpendicularly from the cavernous arteries and irregular caliber (arteriolar
impotence). In the same group patients with reduced cavernous artery inflow also
showed normal or pathological arteriolar components (pre-penile arterial
impotence and diffused penile arterial impotence). CONCLUSIONS: Power Doppler
sonography allows a precise study of the morphodynamics of the cavernous arteries
and helicine arterioles. Our preliminary data suggest that the intracavernous
arteriolar component may have a significant role in the genesis of some forms of
vasculogenic impotence.
PMID- 9649257
TI - Yohimbine for erectile dysfunction: a systematic review and meta-analysis of
randomized clinical trials.
AB - PURPOSE: Erectile dysfunction is a common problem, particularly in diabetics. It
is associated with a considerable burden of suffering. No generally accepted drug
treatment exists. We systematically reviewed and meta-analyzed all randomized,
placebo controlled trials of yohimbine monotherapy for erectile dysfunction to
determine its therapeutic efficacy. Our secondary aim was to evaluate the safety
of yohimbine. MATERIALS AND METHODS: We used computerized literature searches and
standardized data extraction to rate methodological quality in a meta-analysis
using computer statistical software. RESULTS: Seven trials fit the predefined
inclusion criteria. Overall methodological quality of these studies was
satisfactory. The meta-analysis demonstrated that yohimbine is superior to
placebo in the treatment of erectile dysfunction (odds ratio 3.85, 95% confidence
interval 6.67 to 2.22). Serious adverse reactions were infrequent and reversible.
CONCLUSIONS: The benefit of yohimbine medication for erectile dysfunction seems
to outweigh its risks. Therefore, yohimbine is believed to be a reasonable
therapeutic option for erectile dysfunction that should be considered as initial
pharmacological intervention.
PMID- 9649258
TI - Successful sperm retrieval by percutaneous epididymal and testicular sperm
aspiration.
AB - PURPOSE: We evaluated the safety and efficacy of percutaneous sperm aspiration
from the epididymis or testicle as a diagnostic technique to confirm sperm
production and as a therapeutic technique to harvest sperm for use in
intracytoplasmic sperm injection. MATERIALS AND METHODS: We present our
experience with 69 sperm aspiration procedures in men considered to have
nonreconstructible obstructive azoospermia. This short outpatient procedure was
performed using a butterfly needle with the patient under intravenous sedation
and local anesthesia. RESULTS: Of the 32 diagnostic aspirations 20 demonstrated
mature and motile sperm, 9 maturation arrest and 3 germ cell aplasia. In 35 of 37
therapeutic sperm aspirations (95%) adequate samples of sperm after processing
(mean of 5.4 million) were obtained. Of 24 epididymal aspirations 13 (54%) had
sufficient residual sperm for cryopreservation of 1 to 5 vials (mean 2.5)
containing an average of 170,000 sperm per vial. In the 32 intracytoplasmic sperm
injection cycles 221 of 392 eggs (56.3%) fertilized (2PN) and 6 resulted in
ongoing pregnancies (21.4% per transfer). There have been no acute or chronic
complications in this patient population. Ten men underwent a second successful
aspiration procedure for intracytoplasmic sperm injection and 3 underwent a third
aspiration without added difficulty. CONCLUSIONS: Percutaneous epididymal or
testis sperm aspiration is a minimally invasive sperm retrieval technique and
appears to be an effective alternative to microsurgical epididymal sperm
aspiration, which is more invasive, costly and technically difficult.
PMID- 9649259
TI - Effect of exogenous testosterone on prostate volume, serum and semen prostate
specific antigen levels in healthy young men.
AB - PURPOSE: We investigate and define the effects of exogenous testosterone on the
normal prostate. MATERIALS AND METHODS: A total of 31 healthy volunteers 21 to 39
years old were randomized to receive either 100, 250 or 500 mg. testosterone via
intramuscular injection once a week for 15 weeks. Baseline measurements of serum
testosterone, free testosterone and prostate specific antigen (PSA) were taken at
week 1. Semen samples were also collected for PSA content and prostate volumes
were determined by transrectal ultrasound before testosterone injection. Blood
was then drawn every other week before each testosterone injection for the 15
weeks, every other week thereafter until week 28 and again at week 40. After the
first 15 weeks semen samples were again collected, and prostate volumes were
determined by repeat transrectal ultrasound. RESULTS: Free and total serum
testosterone levels increased significantly in the 250 and 500 mg. dose groups.
No significant change occurred in the prostate volume or serum PSA levels at any
dose of exogenous testosterone. Total semen PSA levels decreased following
administration of testosterone but did not reach statistical significance.
CONCLUSIONS: Despite significant elevations in serum total and free testosterone,
healthy young men do not demonstrate increased serum or semen PSA levels, or
increased prostate volume in response to exogenous testosterone injections.
PMID- 9649260
TI - Age specific prostate specific antigen reference ranges: population specific.
AB - PURPOSE: We determined whether 60 to 79-year-old men with a negative digital
rectal examination and a serum prostate specific antigen (PSA) within age
specific PSA reference ranges could safely forgo prostate biopsy. MATERIALS AND
METHODS: We reviewed the medical records of all 60 to 79-year-old men at the
Brooklyn Veterans Administration Medical Center who had a PSA assay, digital
rectal examination and subsequent prostate biopsy for an abnormal rectal
examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August
1995. We compared our results using the standard reference range of 0 to 4.0
ng./ml. with those obtained had we used any of 4 different age specific PSA
reference ranges. RESULTS: We performed 1,280 prostate biopsies in 1,046 men with
available PSA and digital rectal examination data. Using age specific PSA
reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73
avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of
15 (60%) undetected cancers had unfavorable histology. Results were not
statistically significantly different among the 4 age specific PSA reference
ranges. Regarding race, cancer detection rates were significantly higher for
black compared with white men but there was no statistically significant
difference for missed cancers or missed cancers with unfavorable histology.
CONCLUSIONS: In contrast to previous reports of unfavorable histological
characteristics in only 5% of missed cancers using age specific PSA reference
ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We
conclude that age specific PSA reference ranges did not safely eliminate the need
for prostate biopsy in our study population. In 60 to 79-year-old men with a
negative digital rectal examination we continue to use PSA greater than 4.0
ng./ml. as an indication for prostate biopsy.
PMID- 9649261
TI - Influence of finasteride on free and total serum prostate specific antigen levels
in men with benign prostatic hyperplasia.
AB - PURPOSE: Finasteride therapy for benign prostatic hyperplasia (BPH) results in a
marked lowering of serum prostate specific antigen (PSA) levels. However, little
is known about the effect of finasteride on unbound or free serum levels of PSA.
Such information would be important since percent free PSA may substantially
improve the cancer specificity of PSA testing. Thus, we prospectively studied the
effect of finasteride therapy on total and free serum PSA levels. MATERIALS AND
METHODS: In a randomized, placebo controlled, double-blind trial 40 men with
histologically confirmed BPH (age range 52 to 78 years) were treated with either
5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months.
Prostate volume was assessed by transrectal ultrasound. Serum levels of free and
total PSA were measured from archived serum samples stored at -70C at baseline
and for as long as 9 months of treatment. RESULTS: In the finasteride group mean
total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6
months of treatment (50% decrease, p <0.01). In the placebo group, with similar
baseline levels, no significant change was observed. PSA density declined
significantly in finasteride treated men (p <0.01) but not in men receiving
placebo. The mean percent free PSA (13 to 17% at baseline) was not altered
significantly by finasteride or placebo. CONCLUSIONS: Total PSA serum levels
decreased by an average of 50% during finasteride therapy but percent free PSA
did not change significantly. This information is potentially useful in the
interpretation of PSA data used for early detection of prostate cancer in men
receiving finasteride. However, further studies are required to demonstrate the
use of percent free PSA to detect the development of cancer.
PMID- 9649262
TI - Transurethral resection of the prostate versus transurethral electrovaporization
of the prostate: a blinded, prospective comparative study with 1-year followup.
AB - PURPOSE: Transurethral electrovaporization of the prostate has been increasingly
used as a surgical adjunct in the management of men with lower urinary tract
symptoms. In this prospective study we compare the safety and efficacy of
transurethral resection of the prostate and electrovaporization. MATERIALS AND
METHODS: We compared 32 consecutive men (mean age 68.9 years) with lower urinary
tract symptoms treated by transurethral electrovaporization of the prostate to a
cohort of 32 men (mean age 72.8 years) treated by transurethral resection of the
prostate. Parameters of evaluation included American Urological Association
symptom score, peak urinary flow rate, adverse events, including serial changes
in serum hematocrit and sodium, operative time, postoperative catheterization
time, hospitalization time and days lost from work. The data were analyzed by an
investigator who was blinded to which procedure was performed. RESULTS: A total
of 61 patients were evaluable for followup at 1 year. None required retreatment.
At 1 year symptom score decreased 12.8 (66% of patients) and 12.2 (67%) and peak
urinary flow increased 9.7 ml. per second (135%) and 11.3 ml. per second (136%)
for electrovaporization and resection, respectively, (p <0.001). Operative time
was significantly longer with electrovaporization than with resection (47.6 +/-
17.6 versus 34.6 +/- 11.2 minutes, p <0.003). Catheterization time (67.4 +/- 13.6
versus 12.9 +/- 4.6 hours), hospitalization time (2.6 +/- 0.9 versus 1.3 +/- 0.5
days) and days lost from work (18.4 +/- 7.6 versus 6.7 +/- 2.1) were
significantly greater for resection than electrovaporization, respectively. There
were no major complications in the electrovaporization group while in the
resection group 1 patient required transfusion (5 units) and in 1 a clinical
transurethral resection syndrome developed. Potency and retrograde ejaculation
were normal in 18 of 18 patients (100%) and 13 of 17 (76%) after resection and 19
of 20 (95%) and 17 of 20 (85%) after electrovaporization. CONCLUSIONS: The
results indicate that transurethral resection and transurethral
electrovaporization of the prostate are effective in reducing lower urinary tract
symptoms with similar preservation of sexual function. Both significantly improve
peak urinary flow, although resection to a greater degree. Postoperative
morbidity, catheterization time, hospitalization time and days lost from work
were significantly less, and operative time was significantly longer with
electrovaporization. Further studies are underway to determine the long-term
durability of response of transurethral electrovaporization of the prostate
relative to transurethral resection.
PMID- 9649263
TI - Transurethral microwave thermotherapy for benign prostatic hyperplasia: clinical
outcome after 4 years.
AB - PURPOSE: We describe long-term results of transurethral microwave thermotherapy.
We determined pretreatment variables favorable for the outcome. MATERIALS AND
METHODS: We followed for 4 years 187 patients treated with Prostatron software
2.0.* Preoperative evaluations consisted of score, cystoscopy, transrectal
ultrasonography, urine flow and residual volume measurements. Followup
examinations with score and urodynamics were performed for 4 years after
transurethral microwave thermotherapy. Kaplan-Meier plots and logistic regression
were used for statistical analyses. RESULTS: A decrease in the number of
satisfied patients was noted from 62% at 1 year after transurethral microwave
thermotherapy to 23% at 4 years. Initial decrease in score and increase in urine
flow were followed by increase in score and decrease in flow at the 4-year
followup of the 56 patients who had not received supplementary benign prostatic
hyperplasia (BPH) treatment. The Kaplan-Meier analysis estimated the median time
for need of supplementary BPH treatment to be 45 months. Pretreatment urine flow
greater than 10 ml. per second and an irritative score less than 5 were the only
factors related to a favorable outcome. Prostate volume or energy delivered to
the prostate did not influence the result. CONCLUSIONS: Four years after
transurethral microwave thermotherapy 23% of the initially treated group were
satisfied with the result. Two-thirds had received supplementary BPH treatment.
Preoperatively less obstructed patients and those with low initial irritative
scores responded more favorably to transurethral microwave thermotherapy
treatment.
PMID- 9649264
TI - Endothelial cell proliferation activity in benign prostatic hyperplasia and
prostate cancer: an in vitro model for assessment.
AB - PURPOSE: Urinary excretion of several pro-angiogenic and antiangiogenic
substances has been correlated with malignant tumor growth. The aim of this study
was to assay angiogenic activity in urine from patients with cancer of the
prostate and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Urine
specimens from 22 healthy male volunteers (control), 33 patients with BPH and 29
with organ confined prostate cancer were analyzed for angiogenic activity in a
bovine capillary endothelial cell proliferation assay. In parallel the
concentration of basic fibroblast growth factor and vascular endothelial growth
factor was determined by enzyme immunoassay in the corresponding urine specimens.
RESULTS: Urine samples from patients with BPH and prostate cancer increased
bovine capillary endothelial cell proliferation by 13.1% and 15.1%, respectively,
whereas urine from the control group showed a significantly lower angiogenic
activity, increasing endothelial cell proliferation by only 0.7% (p = 0.001).
Urinary basic fibroblast growth factor and vascular endothelial growth factor
were highest in patients with BPH and lowest in the group with prostate cancer (p
= 0.0001). CONCLUSIONS: Urine from patients with BPH and prostate cancer
stimulates endothelial cell proliferative activity. The degree of endothelial
cell stimulation does not correlate with the concentration of basic fibroblast
growth factor or vascular endothelial growth factor. Whether the observed pro
angiogenic activity is due to an increased production or release of (an) other
angiogenic factor(s) and/or loss of (an) angiogenesis inhibitor(s), deserves
further investigation.
PMID- 9649265
TI - Two consecutive sets of transrectal ultrasound guided sextant biopsies of the
prostate for the detection of prostate cancer.
AB - PURPOSE: We investigated the role of performing 2 consecutive sets of transrectal
ultrasound guided sextant biopsies of the prostate in a single office visit as
the protocol for detecting prostate cancer in men presenting for the first time
with an abnormal digital rectal examination and/or elevated serum prostate
specific antigen (PSA). MATERIALS AND METHODS: A total of 137 consecutive men
presenting for the first time with a clinically localized prostate nodule on
digital rectal examination and/or elevated serum PSA based upon age specific
reference ranges underwent 2 consecutive sets of sextant prostate biopsies under
transrectal ultrasound guidance in a single office visit. The 2 sets of biopsies
were processed and analyzed separately by pathologists. RESULTS: Adenocarcinoma
of the prostate was diagnosed in 43 of the patients (31%) undergoing biopsy.
Adenocarcinoma of the prostate was diagnosed in only the second set of biopsies
in 13 cases (10%). High grade prostatic intraepithelial neoplasia without
adenocarcinoma of the prostate was observed in 18 of the first set of biopsies
(15%). High grade intraepithelial neoplasia without adenocarcinoma of the
prostate was the only pathological diagnosis in the second set of biopsies in 3
cases. The second set of biopsies provided important new clinical information
related to prostate cancer in 20 cases (28%) and increased the number of cancers
detected by 30%. In addition, 14 patients with high grade intraepithelial
neoplasia who would have required a second set of biopsies were found not to have
adenocarcinoma of the prostate. Prostate cancer was detected in 43, 27 and 24% of
men with prostate volumes less than 30, 30 to 50 and greater than 50 cc,
respectively. The percentage of prostate cancers detected only in the second set
of biopsies was not significantly related to prostate size. CONCLUSIONS: Two
consecutive sets of transrectal ultrasound guided sextant biopsies of the
prostate performed in a single office visit represent a cost-effective biopsy
strategy for men presenting with an abnormal digital rectal examination and/or
elevated serum PSA. The benefits include increasing the detection of
adenocarcinoma of the prostate and providing the recommended second set of
biopsies for high grade intraepithelial neoplasia without increased morbidity or
cost.
PMID- 9649266
TI - Preliminary outcomes following cryosurgical ablation of the prostate in patients
with clinically localized prostate carcinoma.
AB - PURPOSE: Cryosurgical ablation of the prostate is a novel therapeutic modality
that induces cell lysis in the prostate by direct application of low
temperatures. We have been conducting an ongoing prospective pilot study of the
use of cryosurgical prostate ablation in treating patients with nonmetastatic
prostate adenocarcinoma since January 1993. Results in 145 consecutive patients
with mean 36 months and minimum 12 months of followup are presented. MATERIALS
AND METHODS: Accrual was open to patients with clinical stages T1a to T3c
prostate adenocarcinoma. Pelvic lymph node dissections were recommended but not
required for patients with prostate specific antigen (PSA) greater than 15
ng./ml. before study entry. PSA changes, random prostate biopsy findings and
morbidities after cryosurgical prostate ablation were recorded for each patient.
RESULTS: Overall actuarial rates at 42 months for maintaining PSA less than 0.3
and less than 1.0 were 59% and 66%, respectively. The overall actuarial
progression-free rate at 60 months was 56%. Among 160 biopsies performed 16%
showed some evidence of residual carcinoma. Overall crude rates of maintaining
either a negative biopsy or PSA less than 0.3 at 6 and 24 months after
cryosurgical prostate ablation were 87% and 73%, respectively. Significantly
higher morbidities were seen in previously radiated patients undergoing
cryosurgical prostate ablation compared to those with no prior radiation. Among
nonradiated patients 85% experienced no significant morbidity after cryosurgical
prostate ablation. CONCLUSIONS: Although preliminary, short-term outcomes after
cryosurgical prostate ablation appear to be comparable to identical outcomes
reported for external beam radiotherapy. Based on these results cryosurgical
prostate ablation appears to be an effective therapeutic alternative for treating
patients with localized prostate adenocarcinoma.
PMID- 9649267
TI - Simple reinforcement for thin nephrostomy catheters.
AB - PURPOSE: Nephrostomy catheters are prone to kinking or damage because the thin,
flexible silicone tube is too vulnerable against mechanical stress even when the
proximal end is carefully fixed. We developed a simple method to reinforce the
outside part of a thin catheter protruding from the skin. MATERIALS AND METHODS:
We treated 7 children with nephrostomy catheters or ureteral stents with a
diameter of 8F or smaller. After insertion a large plastic tube was wrapped
around the small catheter, and fixed to the skin and to the peripheral collection
system with adhesive tape. RESULTS: Handling of the catheters improved and there
was less need for re-fixation. CONCLUSIONS: Thin nephrostomy catheters can be
effectively protected by wrapping them into a larger, outer tube after insertion.
PMID- 9649268
TI - Nephron sparing management of Fraley's syndrome with a pyelopyelostomy.
AB - PURPOSE: We describe a new technique for nephron sparing management of
functionally significant vascular compression of the upper pole
infundibulocaliceal system (Fraley's syndrome). MATERIALS AND METHODS: Two
patients evaluated for debilitating, narcotic dependent flank pain had
significant upper pole infundibulocaliceal obstruction resulting from aberrant
major arterial branches entering the hilum dorsally. Reconstructive surgery
consisted of dismembered pyelopyelostomy with transposition of the crossing
vessels in both patients. RESULTS: Pain relief was immediate and complete in both
patients. Followup radiographic evaluation at 1 and 12 months, respectively, has
also documented resolution of the obstruction. CONCLUSIONS: Vascular compression
causing obstruction of the superior infundibulum can cause debilitating pain.
Pathophysiologically operative intervention can be nephron sparing and gratifying
for the surgeon and the patient.
PMID- 9649269
TI - Obstruction of the renal pelvis due to an insoluble blood clot after epsilon
aminocaproic acid therapy: resolution with intraureteral streptokinase
instillations.
AB - PURPOSE: We demonstrate the effectiveness of intraureteral streptokinase
instillations for the resolution of an insoluble blood clot in the renal pelvis.
MATERIALS AND METHODS: A patient with renal adenocarcinoma had prolonged
hematuria related to involvement of the "pyelum" by the tumor. An insoluble blood
clot obstruction of the left renal collecting system developed as a consequence
of epsilon aminocaproic acid therapy, which was treated with low dose
streptokinase through a ureteral catheter. RESULTS: Complete resolution of the
clot and obstruction occurred within 3 days of therapy. CONCLUSIONS: This
relatively simple approach should be used for the treatment of obstruction before
radical surgery is performed.
PMID- 9649270
TI - Bladder leak point pressure: the measure for sphincterotomy success in spinal
cord injured patients with external detrusor-sphincter dyssynergia.
AB - PURPOSE: Transurethral resection of the external sphincter in patients with
spinal cord injury and detrusor-external sphincter dyssynergia has high failure
and reoperation rates. Retrospectively we examined elevated bladder leak point
pressure after transurethral resection of the external sphincter as an indicator
of failure. MATERIALS AND METHODS: A total of 55 spinal cord injury patients
(mean age 50 years) underwent 1 or more sphincter resections, most recently a
mean of 11 years ago. We reviewed the most recent urodynamic studies for bladder
leak point pressure, bladder compliance and persisting external detrusor
sphincter dyssynergia. Each patient was assessed for the presence of an
indwelling catheter, upper tract damage, stones, bacteriuria, autonomic
dysreflexia and vesicoureteral reflux. The incidence of each of these urodynamic
and clinical parameters among patients with bladder leak point pressure less than
40 cm. water was compared to the incidence among those with bladder leak point
pressure greater than 40 cm. water. RESULTS: Patients with bladder leak point
pressure greater than 40 cm. water had a significantly higher incidence of upper
tract damage (p = 0.021) and persisting external detrusor-sphincter dyssynergia
(p = 0.00008). The incidence of an indwelling catheter was no different between
patients with bladder leak point pressure less than and greater than 40 cm.
water. CONCLUSIONS: Bladder leak point pressure greater than 40 cm. water is a
valid indicator of failure of transurethral resection of the external sphincter
since there is a significantly higher incidence of upper tract damage and
persisting external detrusor-sphincter dyssynergia in these patients. Patients
with favorable urodynamic parameters after transurethral resection of the
external sphincter but with indwelling catheters were poorly selected for this
procedure. Furthermore, those without an indwelling catheter after transurethral
resection of the external sphincter may still have adverse urodynamic parameters
and are at significant risk for upper tract damage.
PMID- 9649271
TI - Anuria and acute renal failure resulting from indinavir sulfate induced
nephrolithiasis.
PMID- 9649272
TI - Perinephric abscess masquerading as an angiomyolipoma.
PMID- 9649273
TI - Shock wave lithotripsy during pregnancy: a successful clinical experiment.
PMID- 9649274
TI - Lymphoepithelioma-like carcinoma of the ureter.
PMID- 9649275
TI - Ureteral intussusception by invasive transitional cell carcinoma.
PMID- 9649276
TI - Metastatic Crohn's disease involving penile skin.
PMID- 9649277
TI - Primary leiomyosarcoma of the epididymis and late recurrence on the penis.
PMID- 9649278
TI - Subspecialization, recruitment and retirement trends of American urologists.
AB - PURPOSE: Trends of urology workforce, subspecialization, recruitment practices,
retirement planning, practice characteristics and managed care impacts in the
United States were assessed. MATERIALS AND METHODS: In February 1996 the
executive interviewing branch of The Gallup Organization selected randomly and
interviewed by telephone 507 practicing urologists in the United States who had
provided urological patient care for more than 20 hours per week, practiced in
1995 and completed a urological residency program. RESULTS: Several important
issues emerged. Urologists think we may be training too many urologists,
subspecialty board certification would be a divisive issue to urology as a whole
and 90% of urologists have an active retirement plan, although 23% are not
funding the plan fully. CONCLUSIONS: The American Urological Association Gallup
Poll, as refined by the Health Policy Survey and Research Committee, continues to
be a unique and valuable tool in assessing practice patterns, gathering
demographic data and measuring opinions of the American urologist. This
information will help us chart our way to the twenty-first century.
PMID- 9649279
TI - Re: Bilateral ureteral obstruction after asymptomatic appendicitis.
PMID- 9649280
TI - Re: Bladder prolapse in a female infant with complete epispadias.
PMID- 9649281
TI - Re: The current level of involvement of urological trainees and faculty in
clinical kidney transplantation in the United States and Canada.
PMID- 9649282
TI - Report of the American Society of Nephrology meetings.
AB - PURPOSE: We summarize presentations on topics of interest to the pediatric
urologist from the annual meeting of the American Society of Nephrology, November
1996. MATERIALS AND METHODS: We reviewed all abstracts submitted for presentation
and subsequently published in abstract form. Only those abstracts containing
information pertinent to the field of pediatric urology were summarized for this
report. RESULTS: A total of 24 abstracts addressing a variety of topics were
summarized. Obstructive uropathy was represented by the greatest number of papers
and reflects the multiple investigative efforts currently evaluating the cellular
aspects of this disorder. The genetic basis of hypercalciuria and the impact of
water metabolism on nephroliathisis were also discussed. CONCLUSIONS: Clinical
and basic research activities that are of mutual interest to pediatric urologists
and nephrologists are being conducted. The topic of obstructive uropathy has
received the greatest attention during the last year. However, additional
research, potentially collaborative in nature, on topics such as nephroliathisis
and reflux nephropathy should be encouraged.
PMID- 9649283
TI - 99mTechnetium-dimercapto-succinic acid renal scan in the evaluation of potential
long-term renal parenchymal damage associated with extracorporeal shock wave
lithotripsy in children.
AB - PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) has been reported as
efficient and safe in children. Because of reports of renal parenchymal damage in
adults, this study was designed to assess the effects of ESWL in pediatric
kidneys evaluated before and after treatment with (99m)technetium dimercapto
succinic acid (DMSA) renal scan. MATERIALS AND METHODS: A total of 15 children, 9
months to 15 years old (mean age 6.5 years), underwent ESWL treatment for
urolithiasis. Evaluation imaging included plain abdominal radiography, excretory
urogram and/or renal sonography. DMSA renal scan was performed 24 hours before
ESWL and at least 6 months after treatment. RESULTS: ESWL was performed in 1
session for 8 patients, 2 sessions for 6 and 3 sessions for 1, delivering a range
of 600 to 3,000 shock waves per session. Treatment was successful in achieving
stone-free status in 87% of the cases. Long-term followup (1 to 5 years) showed
no blood pressure changes. On DMSA renal scan no acquired parenchymal scar was
identified at least 6 months after ESWL treatment. CONCLUSIONS: The efficacy of
ESWL in treating pediatric urolithiasis is confirmed. Renal parenchymal trauma
associated with ESWL does not appear to cause long-term lesions identifiable by
DMSA renal scan.
PMID- 9649284
TI - Transverse retubularized ileum: early clinical experience with a new second line
Mitrofanoff tube.
AB - PURPOSE: Transverse retubularization of small ileal segments has been described
as a new time and labor saving variation of the Mitrofanoff principle in a dog
model with good functional results. We report our initial clinical experience
with this technique. MATERIALS AND METHODS: From May 1996 through January 1997 a
new technique of channel formation for intermittent catheterization was applied
in 9 children (1 to 16 years old) and 7 adults (18 to 56) with various
abnormalities of the lower urinary tract. The new method was used in primary
reconstruction of the lower urinary tract and in revision procedures. An ileal
segment 2 cm. long was excised. The bowel wall was opened longitudinally about 1
cm. from the mesentery. The resulting rectangle was retubularized over a 14F
catheter in transverse direction. The longer portion of the tube was implanted
submucosally into the native bladder, the augmented bladder or an intestinal
reservoir. The shorter portion was used to form the stoma. In 4 patients we
created a double tube. RESULTS: Of the patients 13 (81%) are completely continent
day and night with easy catheterization postoperatively. In 2 cases of tunnel
failure continuous leakage required reimplantation of the intact ileal tube to
achieve continence. Minor leakage with bladder fullness in an 11-year-old boy
could be obviated by adjusting the interval of catheterization. CONCLUSIONS: With
the advantage of constant availability, minimal loss of bowel, relative
simplicity (no mesentery interfering with implantation, high tube mobility),
minimized risk of stone formation (no staples), reliable continence (no leak
point) and easy catheterization (longitudinal folds), this straightforward
technique is an excellent second choice use of the Mitrofanoff principle.
PMID- 9649285
TI - Alternatives to appendix in construction of a Mitrofanoff stoma.
PMID- 9649286
TI - Reconstruction and undiversion of the short or severely dilated ureter: the
antireflux ileal nipple revisited.
AB - PURPOSE: Patients undergoing reconstruction of short or severely dilated
aperistaltic ureters are at significant risk for mechanical or functional
obstruction and reflux, particularly when the ureters are being reimplanted into
gastric or intestinal segments. For this problem we describe a simple handsewn,
"stapleless" antireflux ileal nipple, which serves as a useful bridge between a
short ureter and the bladder or reservoir. MATERIALS AND METHODS: A total of 12
patients, 4 to 42 years old (mean age 19), 9 with severely dilated and 3 with
short ureters have received the stapleless antireflux ileal nipple as part of
various reconstructive efforts. Briefly, a 12 to 15 cm. segment of ileum is
isolated and the mesentery is stripped from the middle 8 cm. of the isolated
segment, preserving the blood supply to the proximal and distal 2 cm. of ileum.
Intussusception is created and maintained with multiple (5 to 7) circumferential
rows of 4 to 6 interrupted seromuscular stitches of 3-zero silk. RESULTS: Mean
followup is 27.5 months (range 6 to 60). Upper tract dilatation has stabilized or
improved in all patients, deteriorating temporarily in 1 who had distal nipple
stenosis. All patients underwent followup video urodynamic studies, which
demonstrated no reflux. Nipple related complications included nipple stenosis in
1 patient and dessusception in another. Both complications were corrected without
sequelae. Ureteroileal stenosis or stone formation has not occurred. CONCLUSIONS:
The stapleless antireflux ileal nipple is safe and reliable in preventing reflux.
It is a versatile adjunct to urinary reconstruction in patients with short or
severely dilated, aperistaltic ureters in whom the alternative of a tapered
reimplantation into a segment of bowel or stomach poses a significant
complication threat.
PMID- 9649287
TI - Soluble interleukin-2 receptor in children with reflux nephropathy.
AB - PURPOSE: Serum soluble interleukin-2 receptor level is a sensitive and
quantitative marker of lymphocyte activation. We determined levels of serum
soluble interleukin-2 receptor in children with reflux nephropathy to evaluate
its clinical significance in the prediction for the progression of renal
injuries. MATERIALS AND METHODS: Serum soluble interleukin-2 receptor values were
determined in 63 children with reflux nephropathy. The group consisted of 37 boys
and 26 girls 10 to 18 years old. T cells (naive and memory), B cells and
macrophages were evaluated immunohistochemically in the scarred kidneys of 4
other patients (3 boys and 1 girl 5 to 16 years old) who underwent nephrectomy
due to severe reflux nephropathy with little function seen on (99m)technetium
dimercapto-succinic acid (DMSA) renal scan. Levels of serum soluble interleukin-2
receptor were measured by an enzyme-linked immunosorbent assay. We simultaneously
determined serum levels of creatinine and beta2-microglobulin, and urinary levels
of alpha1-microglobulin and microalbumin. Individual functions of the right and
left kidneys were estimated by renal dimercaptosuccinic acid uptake. RESULTS:
Levels of serum soluble interleukin-2 receptor in the patients who had low total
uptake of DMSA (right uptake plus left uptake) were significantly higher than
those from patients with normal total uptake. Levels of serum soluble interleukin
2 receptor correlated significantly with levels of creatinine (r=0.616, p
<0.0001) and beta2-microglobulin (r=0.803, p <0.0001), and levels of urinary
alpha1-microglobulin (r=0.753, p <0.0001) and microalbumin (r=0.673, p <0.0001).
A significant negative correlation was observed between levels of serum soluble
interleukin-2 receptor and total DMSA uptake values (right uptake plus left
uptake r=-0.678, p <0.0001). In the scarred kidneys leukocyte infiltrates were
markedly increased in fibrosed spaces. The predominant cell type in these lesions
was memory T cells. CONCLUSIONS: These results suggest that elevated levels of
serum soluble interleukin-2 receptor are likely to reflect activated T cells in
the kidneys of patients with reflux nephropathy and may be a useful predictor of
progression of renal injury in these children.
PMID- 9649288
TI - Analysis of testicular migration during the fetal period in humans.
AB - PURPOSE: We present an analysis concerning the testicular migration and its
position correlated to body weight, crown-rump length and gestational age during
the fetal period in humans without congenital abnormalities. MATERIALS AND
METHODS: We studied bilaterally 142 testes taken from 71 fresh human fetuses
between 10 and 35 weeks after conception. The fetuses were also evaluated in
regard to crown-rump length and body weight. The position of the testes was
correlated to the fetal parameters. RESULTS: In 37 fetuses (74 testes) at 10 to
23 weeks after conception only 7 testes (9.45%) had migrated from the abdomen and
were situated in the inguinal canal, in 19 fetuses (38 testes) at 24 to 26 weeks
after conception 22 testes (57.9%) had migrated from the abdomen and in 9 fetuses
(18 testes) at 27 to 29 weeks after conception only 3 testes (16.7%) had not
descended to the scrotum. The testes had not descended into the scrotum in any
fetus weighing 990 gm. or less and with a crown-rump length of 24.5 cm. or less.
On the other hand, in all fetuses weighing more than 1,220 gm. and with a crown
rump length of more than 27.5 cm. the testis was in the scrotum. CONCLUSIONS:
Until 23 weeks after conception the majority of testes remain in the abdomen. The
more intense migration of the testes through the inguinal canal occurred between
21 and 25 weeks after conception. After 30 weeks after conception all testes were
descended to the scrotum in all fetuses.
PMID- 9649289
TI - Immunolocalization of apolipoprotein D, androgen receptor and prostate specific
antigen in early stage prostate cancers.
AB - PURPOSE: To determine the cellular distribution and levels of immunohistochemical
staining for apolipoprotein D (Apo-D), prostate specific antigen (PSA) and
androgen receptor (AR) in early stage prostate cancers. MATERIALS AND METHODS:
Cellular distribution of Apo-D, PSA and AR in 30 stage A/B prostate cancers and
in non-malignant glandular tissue contained in the same sections was detected
immunohistochemically, and staining was evaluated by computerized video image
analysis. RESULTS: Staining for Apo-D (percentage positive cellular area) was
significantly increased in tumor cells of early stage prostate cancers compared
with non-malignant glandular tissue. PSA and AR were present at high levels in
both early stage prostate tumors and non-malignant prostate. CONCLUSIONS:
Malignant transformation in the prostate is associated with increased cellular
levels of Apo-D.
PMID- 9649290
TI - Sex differences in function and distribution of beta-adrenoceptors in rabbit
urinary bladder.
AB - PURPOSE: To examine whether there are sex-related differences in urinary bladder
function, we evaluated the function and distribution of beta-adrenoceptor in the
male and female rabbit urinary bladder. MATERIALS AND METHODS: Ten male and ten
female rabbits were studied. The function and distribution of beta-adrenoceptors
were studied by measuring changes in contractile forces from isoproterenol, a
beta-adrenoceptor agonist, and forskolin, an adenylate cyclase activator, and by
measuring beta-adrenoceptor densities using radioligand receptor binding
techniques. RESULTS: Isoproterenol caused significantly greater relaxation in
female trigonal muscles than in male trigonal muscles. It caused similar
relaxation responses in the male and female detrusors. The Bmax values for
[3H]dihydroalprenolol (DHA) binding in trigonal muscles were significantly higher
in the female than in the male, whereas Bmax values for [3H]DHA binding in the
male and the female detrusor were similar. In contrast, forskolin caused
similarly marked relaxations in the male and the female detrusor and trigonal
muscles. CONCLUSION: These findings demonstrate that there are sex-related
differences in the function and the distribution of beta-adrenoceptors in rabbit
trigonal smooth muscles.
PMID- 9649291
TI - Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth
medium of P-fimbriated Escherichia coli.
AB - PURPOSE: Vaccinium macrocarpon--the American cranberry--irreversibly inhibits the
expression of P-fimbriae of E. coli. Further effects on the function and
expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid
media laced with cranberry juice. METHODS: Cranberry concentrate at pH 7.0 was
added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17
were plated on this medium with a plain CFA control and incubated at 37C.
Cultures were tested for ability to agglutinate P-receptor specific beads.
Bacteria were washed in PBS and agglutination retested. Cultures were also
replated on plain CFA agar and rechecked for their ability to agglutinate.
Transmission electron micrographs were performed on positive control and test
bacteria. RESULTS: For E. coli strain JR1, P-fimbrial agglutination was inhibited
after the third plating. DS17 was fully inhibited after the second plating.
Washing in PBS did not affect agglutination, but replating on CFA agar allowed
agglutination to recur. Electron micrographic study of control populations
confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression
of fimbriae. Additionally, inhibited bacteria showed cellular elongation.
CONCLUSIONS: Cranberry juice irreversibly inhibits P-fimbriae. Electron
micrographic evidence suggests that cranberry juice acts on the cell wall
preventing proper attachment of the fimbrial subunits or as a genetic control
preventing the expression of normal fimbrial subunits or both.
PMID- 9649292
TI - Renal actions of endothelin-1 under endothelin receptor blockade by BE-18257B.
AB - PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium,
causes profound renal vasoconstriction by binding to ET-A receptors. The present
study examined the renal actions of ET-1 after ET-A receptors were blocked by BE
18257B to unmask the functions of ET-B receptors. MATERIALS AND METHODS: Renal
hemodynamics and clearance measurements were obtained in anesthetized dogs after
intrarenal infusion of BE-18257B at 100 ng./kg./min. (Group 1), after intrarenal
infusion of ET-1 at 2 ng./kg./min. (Group 2), or after intrarenal infusion of ET
1 superimposed on BE-18257B (Group 3). RESULTS: In Group 1, BE-18257B infusion
did not alter arterial pressure, renal blood flow (RBF), GFR or tubular function.
In Group 2, ET-1 infusion led to a significant decrease in RBF and GFR (37 and
40%, respectively) without altering arterial pressure. Urinary volume and sodium
excretion were not changed but osmolality decreased significantly. In Group 3, BE
18257B infusion significantly attenuated the decrease in RBF caused by ET-1 and
increased GFR by 40% without altering arterial pressure, associated with
significant diuresis and natriuresis. CONCLUSION: Renal vasoconstriction caused
by ET-1 is attenuated by ET-A receptor blockade with BE-18257B, which unmasks the
hemodynamic and tubular actions of ET-B receptors. As a result, it limits the ET
1 induced decrease in RBF and raises GFR, and leads to a diuresis and
natriuresis.
PMID- 9649293
TI - Lidocaine prevents noxious excitation of bladder afferents induced by
intravesical capsaicin without interfering with the ensuing sensory
desensitization: an experimental study in the rat.
AB - PURPOSE: The effects of the local anesthetic lidocaine on the noxious excitation
and subsequent desensitization of bladder sensory fibers, produced by
intravesical capsaicin, were evaluated through c-fos activation in the spinal
cord. MATERIALS AND METHODS: Noxious excitation was demonstrated by counting Fos
immunoreactive (IR) cells occurring in the rat spinal cord 2 hours after
intravesical administration of 1 mM. capsaicin, preceded or not by 2% lidocaine.
Desensitization was studied by comparing the number of Fos-IR cells induced by 1%
acetic acid in rats treated 24 hours before with 1 mM. intravesical capsaicin
preceded or not by 2% lidocaine. RESULTS: Lidocaine instilled previously markedly
reduced the number of Fos-IR spinal cells responding to capsaicin-induced bladder
afferent excitation. Numbers of Fos-IR cells induced by acetic acid instillation
in bladders desensitized by capsaicin administrated 24 hours before were not
changed by lidocaine application prior to capsaicin. CONCLUSIONS: These findings
suggest that local anesthetic pretreatment of the bladder with lidocaine reduces
the capsaicin-induced noxious excitation of the sensory fibers without decreasing
their subsequent desensitization.
PMID- 9649294
TI - Effects of MK-801 on bladder overactivity in rats with cerebral infarction.
AB - PURPOSE: Our objective was to evaluate the underlying mechanisms of neurogenic
voiding dysfunction following cerebral infarction. MATERIALS AND METHODS: The
left middle cerebral artery (MCA) was occluded using 4-0 monofilament nylon
thread in male S-D rats. Cystometric examination was performed in unanesthetized
and urethane-anesthetized rats through a catheter chronically implanted in the
dome of the bladder. RESULTS: Bladder capacity of unanesthetized or urethane
anesthetized rats was significantly reduced just after occlusion of the left MCA;
2 weeks after the occlusion, the capacity was less than half that in sham
operated rats. Intravenous administration of N-methyl-d-aspartate (NMDA) receptor
antagonist MK-801 to the unanesthetized sham-operated rats led to a marked dose
dependent decrease in bladder capacity. Its administration to unanesthetized rats
with cerebral infarction resulted in a slight decrease in bladder capacity. In
the urethane-anesthetized state, the bladder capacity of the rats with cerebral
infarction was significantly increased by MK-801, 0.1 mg./kg., without inhibiting
the contraction pressure or increasing the amount of residual urine. A high dose
(1 mg./kg.) of MK-801 was required to increase the bladder capacity of sham
operated rats. This led to an inhibition of contraction pressure and an increase
in residual urine. CONCLUSION: Results in urethane anesthetized rats indicate
that NMDA glutamatergic transmission is important in the overactivity of the
bladder following a cerebral infarction. This model is useful in studying the
neurogenic voiding dysfunction observed in patients with cerebrovascular disease.
PMID- 9649295
TI - Change in bladder contractility associated with bladder overactivity in rats with
cerebral infarction.
AB - PURPOSE: To evaluate the contractile properties of overactive bladder from rats
in the chronic stage of experimental cerebral infarction. MATERIALS AND METHODS:
Cystometry was performed in conscious male S-D rats after inducing occlusion of
the left middle cerebral artery. Bladder muscle strips were evaluated for force
development in response to field stimulation, acetylcholine and KCl. By measuring
the contractile response to field stimulation after adding atropine and
alpha,beta-methylene-ATP, contributions of cholinergic and purinergic
transmission were determined. RESULTS: Bladder capacity of cerebral-infarcted
rats was <50% of the capacity of sham-operated rats and significantly less than
that of sham-operated rats even 4 months after surgery. There was no significant
difference in bladder weight between sham-operated rats and cerebral-infarcted
rats. No differences in the contractile response of detrusor strips to field
stimulation and acetylcholine, or in the relative contribution of cholinergic and
purinergic transmission to the contractile response, were observed over time or
between strips from sham-operated rats and cerebral-infarcted rats. KCl induced
significantly less contraction in strips from 4 month infarcted rats than in
strips from 4 month sham-operated rats, 2 week infarcted rats and 2 month
infarcted rats. CONCLUSIONS: This animal model will be useful for chronic studies
on the mechanism of detrusor hyperactivity (DH).
PMID- 9649296
TI - Methotrexate resistance in human uroepithelial cells with p53 alterations.
AB - PURPOSE: Bladder cancers are frequently treated with combination chemotherapy
that includes methotrexate (MTX). The development of drug resistance is a common
problem in treatment of bladder cancers. We tested if the status of p53 and/or
pRb affects the development of MTX resistance in bladder epithelial cell lines.
MATERIALS AND METHODS: We used two isogeneic sets of cell lines in which we
manipulated the status of p53 and/or pRb by transformation with Human
Papillomavirus (HPV) E6 and/or E7 or with a transdominant TP53 mutant
(TP53(143)). One series of isogeneic origin was derived from normal human
uroepithelial cells (HUC), and the other was derived from a human transitional
cell carcinoma (TCC). Cell lines with p53 and/or pRb alterations were cultured
for six months while increasing the MTX concentration in each line, as resistance
developed. RESULTS: Two cell lines with both pRb and p53 alterations, alphaE6/E7
HUC and alphaE7-HUCp53mu, acquired the greatest resistance (750 nM) to MTX. One
line with p53 loss, E6-TCC#10, acquired intermediate resistance (500 nM), while
two lines, alphaE7-HUC and E7-TCC#10, with altered pRb but wildtype p53, showed
low levels of MTX resistance (125 nM and 80 nM, respectively). Two clear
mechanisms of MTX resistance were identified. All five MTX resistant cell lines
showed altered uptake of MTX. In addition, two of five MTX resistant cell lines,
both with altered p53, showed dihydrofolate reductase (DHFR) amplification.
CONCLUSIONS: p53 alteration increases the risk for development of drug resistance
by both DHFR amplification and altered MTX transport in transformed human bladder
epithelial cell lines.
PMID- 9649297
TI - Effects of epidermal growth factor on the invasion activity of the bladder cancer
cell line.
AB - PURPOSE: Epidermal growth factor (EGF) is excreted in high concentrations in the
urine and stimulates urothelial cell growth. The cultured bladder cancer cell
line KU-1 was used to study the molecular mechanisms by which EGF affects
urothelial tumor growth and invasion activity. MATERIALS AND METHODS: KU-1 cells
were grown in cell culture in the presence or absence of EGF. Anchorage
independent cell growth assays and Matrigel invasion assays were performed.
Expression of cytokeratins was examined by Northern and Western blot analyses.
Chloramphenicol acetyltransferase assays were used to determine whether EGF
stimulated matrix metalloproteinase expression. RESULTS: EGF enhanced anchorage
independent growth in soft agar and increased the number of cells penetrating
into a Matrigel membrane. A transient transfection assay revealed that EGF
increased the promoter activities of the matrix metalloproteinase 1 and 9 genes
in KU-1 cells. Moreover, the morphology of KU-1 cells changed after the addition
of EGF to the culture medium. Western and Northern blot analyses demonstrated
that EGF decreased cytokeratin 19 expression, but did not affect expression of
cytokeratin 8 or 18. CONCLUSION: EGF increased the invasive activity of KU-1
bladder cancer cells in part by increasing the secretion of matrix
metalloproteinases. Morphologic changes may result from altered composition of
cytoskeletal proteins.
PMID- 9649298
TI - Sensitivity of human prostatic carcinoma cell lines to low dose rate radiation
exposure.
AB - PURPOSE: Low dose rate radioemitters, such as 125I, 103Pd, and 89Sr, have been
used both for local and systemic treatment of prostate cancer. Most normal cells
exposed to ionizing radiation characteristically activate cell cycle checkpoints,
resulting in cell cycle arrest at the G1/S and G2/M transition points. Cancer
cells are typically quite sensitive to radiation killing late in the G2 phase of
the replicative cell cycle. Furthermore, most cancer cells accumulating at the
G2/M transition point as a result of low dose rate radiation exposure appear to
become sensitive to further low dose rate irradiation. For this reason,
protracted exposure of cancer cells to low dose rate radiation has been proposed
to result in increased cancer cell killing as compared with brief exposures of
cancer cells to high dose rate radiation. Since many human prostatic carcinomas
contain somatic genome alterations targeting genes which affect the cell cycle
and radiation-associated cell cycle checkpoints, we evaluated the effects of low
dose rate radiation exposure on the cell cycle and on clonogenic survival for
various human prostatic carcinoma cell lines. MATERIALS AND METHODS: Human
prostatic carcinoma cells from the LNCaP, DU 145, PC-3, PPC-1, and TSU-Pr1 cell
lines were exposed to low dose rate (0.25 Gy/hour) or high dose rate (60 Gy/hour)
radiation in vitro and then assessed for radiation cytotoxicity by clonogenic
survival assay. Cell cycle perturbations following protracted exposure to low
dose rate radiation were evaluated using flow cytometry. RESULTS: For LNCaP
cells, low dose rate radiation exposure resulted in an accumulation of cells at
both the G1/S and the G2/M cell cycle transition points. For DU 145, PC-3, PPC-1,
and TSU-Pr1 cells, treatment with low dose rate radiation triggered G2/M cell
cycle arrest, but not G1/S arrest. Unexpectedly, the cell cycle redistribution
pattern phenotypes observed, G1/S and G2/M cell cycle arrest versus G2/M arrest
alone, appeared to have little effect on low dose rate radiation survival.
Furthermore, while PC-3, PPC-1, and TSU-Pr1 cells exhibited increased cytotoxic
sensitivity to low dose rate versus fractionated high dose rate radiation
treatment, DU 145 and LNCaP cells did not. CONCLUSIONS: Radiation-associated
pertubations in replicative cell cycle progression were not dominant determinants
of low dose rate radiation killing efficacy in human prostate cancer cell lines
in vitro.
PMID- 9649299
TI - Improved detection of recurrent bladder cancer using the bard BTA stat test.
PMID- 9649301
TI - Understanding the role of the essential Asp251 in cytochrome p450cam using site
directed mutagenesis, crystallography, and kinetic solvent isotope effect.
AB - Proton transfer in cytochromes P450 is a critical step in the activation of
molecular oxygen. Extensive study of the P450cam active site has identified
several residues that play a central role in dioxygen bond scission. A highly
conserved carboxylate, aspartate-251 in P450cam in the distal helix I,
participates in a series of hydrogen-bond/ion pairs near the molecular surface
and has been implicated in the catalytic mechanism. Mutation of Asp251 is known
to lower activity by 2 orders of magnitude and change the rate-limiting step in
the catalytic cycle, suggesting a role for an acid functionality in generation of
iron-oxygen reactive intermediates. The turnover rates of the Asp251Asn mutant in
various protium-deuterium mixtures have been determined and show a significantly
larger kinetic solvent isotope effect, with an overall magnitude of 10 compared
to 1.8 for the wild-type P450cam. In addition, a much larger number of protons
are involved in the rate-limiting step for the Asp251Asn mutant than in the wild
type enzyme. These results indicate that Asp251 is an essential part of the
normal proton delivery machinery required for O-O bond scission. The crystal
structure of the Aps251Asn mutant obtained from data collected at cryogenic
temperatures has been refined to 1.9 A. Key hydrogen bonds required to hold
Asp251 in position have been broken which allows the mutant Asn251 side chain to
swing out and away from the O2 binding site leading to a more open active site.
This change could allow easier access by water and thus contribute to the
observed kinetic solvent isotope effects.
PMID- 9649302
TI - Active-site binding of glycosides by Thermomonospora fusca endocellulase E2.
AB - The determination of the high-resolution structure of the Thermomonospora fusca
endocellulase E2 catalytic domain makes it ideal for exploring cellulase
structure-function relationships. Here we present binding parameters (Kd, DeltaH
degrees, and DeltaS degrees) describing the interaction of E2 with 4
methylumbelliferyl glycosides, determined by titrating the quenching of ligand
fluorescence in equilibrium binding experiments. Quenched MU(Glc)2/E2 complexes
were used as indicators in displacement titrations to measure the binding of
natural glycosides and also of a nonhydrolyzable cellotetraose analogue. Binding
of MU(Glc)2 and cellotriose were also determined by titration calorimetry. The
results show that E2 binds glycosides exclusively in its active-site cleft, with
high affinity and specificity. The observed patterns of ligand hydrolysis and the
results with MU(Glc)2 as a substrate indicated that ligands bound to E2 with
their nonreducing ends in position -2, consistent with the position of cellobiose
in the E2cd structure. Polymerase chain reaction (PCR) mutagenesis of the
conserved residue Tyr 73 (in E2 binding subsite -1) to Phe and Ser produced
enzymes with lower activity but higher binding affinities, indicating that the
volume of the subsite -1 binding pocket is crucial for enzyme function.
Similarly, MUXylGlc (with its xylosyl unit located in position -1) bound with 100
fold higher affinity than MU(Glc)2. These results are similar to those for the
related Trichoderma reesei exocellulase CBH II. The binding data were compared
with that previously reported for CBH II and interpreted in terms of the
functional differences between endo- and exocellulases.
PMID- 9649303
TI - NMR solution structure of a DNA dodecamer duplex containing a cis
diammineplatinum(II) d(GpG) intrastrand cross-link, the major adduct of the
anticancer drug cisplatin.
AB - The structure of the DNA duplex dodecamer, d(CCTCTGGTCTCC. GGAGACCAGAGG),
containing the cisplatin d(GpG) 1,2-intrastrand cross-link at the position
denoted by asterisks, was determined in solution by high-resolution 2D NMR
spectroscopy and restrained molecular dynamics refinement. The cis
[Pt(NH3)2?d(GpG-N7(1), N7(2))?] lesion causes the adjacent guanine bases to roll
toward one another by 49 degrees, leading to an overall helix bend angle of 78
degrees. These features are more exaggerated than those observed in the X-ray
crystal structure determined for the same platinated duplex [Takahara et al.
(1995) Nature 377, 649-652]. A common property of the solution and crystal
structures is the widening and flattening of the minor groove opposite the
platinum adduct, affording geometric parameters resembling those found in A-form
DNA. This deformation is especially noteworthy for the solution structure because
its sugar puckers are primarily those of B-form DNA. The unwinding of the helix
at the site of platination is 25 degrees. The curvature and shape of the
platinated duplex are remarkably similar to those observed in DNA duplexes
complexed by the HMG-domain proteins SRY and LEF-1. The structure reveals how
cisplatin binding alters DNA in such a manner as to facilitate HMG-domain protein
recognition.
PMID- 9649304
TI - H11-H12 loop retinoic acid receptor mutants exhibit distinct trans-activating and
trans-repressing activities in the presence of natural or synthetic retinoids.
AB - Retinoids, such as the naturally occurring all-trans-retinoic acid (atRA) and
synthetic ligand CD367 modulate ligand-dependent transcription through retinoic
acid receptors (RARs). Retinoid binding to RAR is believed to trigger structural
transitions in the ligand-binding domain (LBD), leading to helix H1 and helix H12
repositioning and coactivator recruitment and corepressor release. Here, we
carried out a detailed mutagenesis analysis of the H11-H12 loop (designated the L
box) to study its contribution to hRARalpha activation process. Point mutations
that reduced transactivation by atRA also reduced atRA-induced transrepression of
AP1 transcription, correlating ligand-induced activation and repression. However,
a correlation was not observed with these mutations when tested with another
ligand CD367, a synthetic agonist with binding properties identical to those of
atRA. Transcription was strongly inhibited in the presence of CD367 for some
mutants, thus leading to an inverse agonist activity of this ligand. None of
these mutations significantly altered binding affinity for either ligand,
indicating that altered transcription was not caused by altered ligand binding by
these mutations. Although simple correlations with transcriptional activities
were not found, these mutations were also characterized by altered ligand-induced
structural transitions, which were distinct for the atRA-hRARalpha or CD367
hRARalpha complexes. These results indicate that amino acids in the L box are
involved in specifying trans-repressive and trans-activating properties of the
hRARalpha, and support the notion that different agonists induce distinct
conformations in the LBD of the receptor.
PMID- 9649305
TI - A single amino acid substitution changes ribonuclease 4 from a uridine-specific
to a cytidine-specific enzyme.
AB - The structural features underlying the strong uridine specificity of ribonuclease
4 (RNase 4) are largely unknown. It has been hypothesized that the negatively
charged alpha-carboxylate is close to the pyrimidine binding pocket, due to a
unique C-terminal deletion. This would suppress the cleavage of cytidine
containing substrates [Zhou, H.-M., and Strydom, D. J. (1993) Eur. J. Biochem.
217, 401-410]. Replacement of the alpha-carboxylate by an alpha-carboxamide in a
fragment complementation system decreased both (kcat/Km)CpA and (kcat/Km)UpA ,
thus refuting the hypothesis. However, model building showed that the deletion
allowed the side chain of Arg-101 to reach the pyrimidine binding pocket. From
the 386-fold reduction in (kcat/Km)UpA in RNase 4;R101N, it is concluded that
this residue functions in uridine binding, analogous to Ser-123 in RNase A. In
addition, it may have an effect on Asp-80. The 2-fold increase in (kcat/Km)CpA in
the mutant R101N and the close proximity of the side chains of Arg-101 and Asp-80
suggested that the latter could be involved in suppressing CpA catalysis. The
substrate specificity of RNase 4;D80A was completely reversed: (kcat/Km)UpA
decreased 159-fold, whereas (kcat/Km)CpA increased 233-fold. The effect on CpA
was unexpected, because the corresponding residue in bovine pancreatic RNase A
(Asp-83) hardly affects cytidine-containing substrates. Furthermore, the residue
is conserved in nearly all sequences of mammalian RNase 1. Thus, an evolutionary
highly conserved residue does not necessarily function in the same way in
homologous enzymes. A model, which proposes that the structure of RNase 4 has
been optimized to permanently fix the position of Asp-80 and impede its movement
away from the pyrimidine binding pocket, is presented.
PMID- 9649306
TI - Novel water-mediated hydrogen bonds as the structural basis for the low oxygen
affinity of the blood substitute candidate rHb(alpha 96Val-->Trp).
AB - One of the most promising approaches for the development of a synthetic blood
substitute has been the engineering of novel mutants of human hemoglobin (Hb) A
which maintain cooperativity, but possess lowered oxygen affinity. We describe
here two crystal structures of one such potential blood substitute, recombinant
(r) Hb(alpha 96Val-->Trp), refined to 1.9 A resolution in an alpha-aquomet, beta
deoxy T-state, and to 2.5 A resolution in a carbonmonoxy R-state. On the basis of
molecular dynamics simulations, a particular conformation had been predicted for
the engineered Trp residue, and the lowered oxygen affinity had been attributed
to a stabilization of the deoxy T-state interface by alpha 96Trp-beta 99Asp
hydrogen bonds. Difference Fourier maps of the T-state structure clearly show
that alpha 96Trp is in a conformation different from that predicted by the
simulation, with its indole side chain directed away from the interface and into
the central cavity. In this conformation, the indole nitrogen makes novel water
mediated hydrogen bonds across the T-state interface with beta 101Glu. We propose
that these water-mediated hydrogen bonds are the structural basis for the lowered
oxygen affinity of rHb(alpha 96Val-->Trp), and discuss the implications of these
findings for future molecular dynamics studies and the design of Hb mutants.
PMID- 9649307
TI - Contribution of domain interface residues to the stability of antibody CH3 domain
homodimers.
AB - Dimers of CH3 domains from human IgG1 were used to study the effect of mutations
constructed at a domain-domain interface upon domain dissociation and unfolding,
"complex stability". Alanine replacement mutants were constructed on one side of
the interface for each of the sixteen interdomain contact residues by using a
single-chain CH3 dimer in which the carboxyl terminus of one domain was joined to
the amino terminus of the second domain via a (G4S)4 linker. Single-chain
variants were expressed in Escherichia coli grown in a fermentor and recovered in
yields of 6-90 mg L-1 by immobilized metal affinity chromatography. Guanidine
hydrochloride-induced denaturation was used to follow domain dissociation and
unfolding. Surprisingly, the linker did not perturb the complex stability for
either the wild type or two destabilizing mutants. The CH3 domain dissociation
and unfolding energetics are dominated by six contact residues where
corresponding alanine mutations each destabilize the complex by >2.0 kcal mol-1.
Five of these residues (T366, L368, F405, Y407, and K409) form a patch at the
center of the interface and are located on the two internal antiparallel beta
strands. These energetically key residues are surrounded by 10 residues on the
two external beta-strands whose contribution to complex stability is small (three
have a Delta DeltaG of 1.1-1.3 kcal mol-1) or very small (seven have a Delta
DeltaG of =0.7 kcal mol-1). Thus, at the center of the CH3 structural interface
there is a small "functional interface" of residues that make significant
contributions to complex stability.
PMID- 9649308
TI - The role of profilin in actin polymerization and nucleotide exchange.
AB - Properties of human profilin I mutated in the major actin-binding site were
studied and compared with wild-type profilin using beta/gamma-actin as
interaction partner. The mutants ranged in affinity, from those that only weakly
affected polymerization of actin to one that bound actin more strongly than wild
type profilin. With profilins, whose sequestering activity was low, the
concentration of free actin monomers observed at steady-state of polymerization
[Afree], was close to that seen with actin alone ([Acc], critical concentration
of polymerization). Profilin mutants binding actin with an intermediate affinity
like wild-type profilin caused a lowering of [Afree] as compared to [Acc],
indicating that actin monomers and profilin:actin complexes participate in
polymer formation. With a mutant profilin, which bound actin more strongly than
the wild-type protein, an efficient sequestration of actin was observed, and in
this case, the [Afree] at steady state was again close to [Acc], suggesting that
the mutant profilin:actin had a greatly lowered ability to incorporate actin
subunits at the (+)-end. The results from the kinetic and steady-state
experiments presented are consonant with the idea that profilin:actin complexes
are directly incorporated at the (+)-end of actively polymerizing actin
filaments, while they do not support the view that profilin facilitates polymer
formation.
PMID- 9649309
TI - Apolipoprotein(a) binds to low-density lipoprotein at two distant sites in
lipoprotein(a).
AB - Lipoprotein(a) [Lp(a)] consists of low-density lipoprotein (LDL) and
apolipoprotein(a) [apo(a)] linked with a disulfide bond. Scanning force
microscopy (SFM) of Lp(a) showed, for the first time, a belt-like structure of
apo(a) with both ends attached to a spherical LDL. The two ends of apo(a) were
bound to the LDL sphere at two distant sites. Occasionally, the ends were
attached to two touching spheres. Under the same imaging conditions, LDL appeared
as individual spheres. Electron microscopy (EM) studies of Lp(a) by several
groups over the past decade failed to reveal this belt-like structure of apo(a).
Images of isolated apo(a) in air or in phosphate buffer showed apo(a) as
individual belts, and these belts tended to crowd together. Lp(a) formed leaf
like aggregates; apo(a) aggregates were fishnet-like, whereas LDL aggregates were
less characteristic. Quantitative analysis of Lp(a) showed the diameter of the
LDL to be 24.8 +/- 8.7 nm (n = 46), which is close to the reported value of 24.2
+/- 4.2 nm found with EM. The length of the belts attached to the spheres was
measured to be 173.5 +/- 6.6 nm (n = 15). I also found, by using a functionalized
tip, that the interaction force between apo(a) and its ligand, lysine, was
related to the ionic strength of the bulk solution. This force can be reduced by
the presence of epsilon-aminocaproic acid.
PMID- 9649310
TI - Active site modifications in a double mutant of liver alcohol dehydrogenase:
structural studies of two enzyme-ligand complexes.
AB - The oxidation of alcohol to aldehyde by horse liver alcohol dehydrogenase (LADH)
requires the transfer of a hydride ion from the alcohol substrate to the cofactor
nicotinamide adenine dinucleotide (NAD). A quantum mechanical tunneling
contribution to this hydride transfer step has been demonstrated in a number of
LADH mutants designed to enhance or diminish this effect [Bahnson, B. J., et al.
(1997) Proc. Natl. Acad. Sci. U.S.A. 94, 12797-12802]. The active site double
mutant Phe93 --> Trp/Val203 --> Ala shows a 75-fold reduction in catalytic
efficiency relative to that of the native enzyme, and reduced tunneling relative
to that of either single mutant. We present here two crystal structures of the
double mutant: a 2.0 A complex with NAD and the substrate analogue
trifluoroethanol and a 2.6 A complex with the isosteric NAD analogue CPAD and
ethanol. Changes at the active site observed in both complexes are consistent
with reduced activity and tunneling. The NAD-trifluoroethanol complex
crystallizes in the closed conformation characteristic of the active enzyme.
However, the NAD nicotinamide ring rotates away from the substrate, toward the
space vacated by replacement of Val203 with the smaller alanine. Replacement of
Phe93 with the larger tryptophan also produces unfavorable steric contacts with
the nicotinamide carboxamide group, potentially destabilizing hydrogen bonds
required to maintain the closed conformation. These contacts are relieved in the
second complex by rotation of the CPAD pyridine ring into an unusual syn
orientation. The resulting loss of the carboxamide hydrogen bonds produces an
open conformation characteristic of the apoenzyme.
PMID- 9649311
TI - Insights into the mechanism of catalysis by the P-C bond-cleaving enzyme
phosphonoacetaldehyde hydrolase derived from gene sequence analysis and
mutagenesis.
AB - Phosphonoacetaldehyde hydrolase (phosphonatase) catalyzes the hydrolysis of
phosphonoacetaldehyde to acetaldehyde and inorganic phosphate. In this study, the
genes encoding phosphonatase in Bacillus cereus and in Salmonella typhimurium
were cloned for high-level expression in Escherichia coli. The kinetic properties
of the purified, recombinant phosphonatases were determined. The Schiff base
mechanism known to operate in the B. cereus enzyme was verified for the S.
typhimurium enzyme by phosphonoacetaldehyde-sodium borohydride-induced
inactivation and by site-directed mutagenesis of the catalytic lysine 53. The
protein sequence inferred from the B. cereus phosphonatase gene was determined,
and this sequence was used along with that from the S. typhimurium phosphonatase
gene sequence to search the primary sequence databases for possible structural
homologues. We found that phosphonatase belongs to a novel family of hydrolases
which appear to use a highly conserved active site aspartate residue in covalent
catalysis. On the basis of this finding and the known stereochemical course of
phosphonatase-catalyzed hydrolysis at phosphorus (retention), we propose a
mechanism which involves Schiff base formation with lysine 53 followed by
phosphoryl transfer to aspartate (at position 11 in the S. typhimurium enzyme and
position 12 in the B. cereusphosphonatase) and last hydrolysis at the imine C(1)
and acyl phosphate phosphorus.
PMID- 9649312
TI - NMR solution structure of the oxidized form of MerP, a mercuric ion binding
protein involved in bacterial mercuric ion resistance.
AB - Mercuric ions are toxic to living organisms because of their strong affinity for
cysteine residues in proteins. Some bacteria have developed a resistance
mechanism whereby Hg2+ is transported into the cytoplasm and reduced to Hg0. One
of the proteins involved in the transport of mercuric ion is the periplasmic
binding protein MerP, which can exist both as oxidized (disulfide) and as reduced
(dithiol) forms. Only the reduced form with Cys-17 and Cys-14 residues as free
thiols is a potent receptor for mercuric ion. In this work the solution structure
of the oxidized form of MerP has been determined by multidimensional NMR
spectroscopy and compared to the NMR structures of the previously published
structures of the reduced and mercury-bound forms of MerP. The mercury-bound and
oxidized forms have similar tertiary structures, whereas in the reduced form
there is a large rearrangement of the mercuric ion binding loop and the nearby
loop comprising residues 38-41. The structural arrangement of the latter loop
seems to be important for the stabilization of the surface location of the
cysteine-containing loop. In the reduced form at low pH the cysteine-containing
loop adopts a conformation similar to what is observed in the oxidized and
mercury-bound forms. The oxidized form also differs with respect to the other two
forms in the relative positions of some of the alpha-helices and beta-strands.
Structural differences between the oxidized and reduced forms may help explain
why the reduced form is stable in the periplasm, which is considered to be an
oxidizing environment.
PMID- 9649313
TI - 13C relaxation and dynamics of the purine bases in the iron responsive element
RNA hairpin.
AB - The iron responsive element (IRE) RNA hairpin contains a conserved six-nucleotide
loop. The NMR structure of this loop showed that the positions of four of its
bases are not tightly constrained, while the remaining two are hydrogen-bonded
[Laing, L. G., and Hall, K. B. (1996) Biochemistry 35, 13586]. To investigate the
flexibility of the RNA in the loop and in the stem, 13C NMR relaxation methods
have been used to describe the dynamics of the purine bases. IRE hairpins
containing [13C]guanosine and [13C]adenosine are used in NMR experiments to
measure T1, T1rho, and NOE values of the bases as a function of temperature (20
37 degreesC). Data are analyzed using the Lipari-Szabo model-free formalism
[Lipari, G., and Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546] to determine order
parameters and time scales of the motion. Results indicate that the purine bases
in the stem have order parameters that are independent of temperature, although
they show evidence of both fast (6-40 ps) motions and slower motions at 37
degreesC. The three purines in the loop exhibit increasingly complex motions with
long (nanoseconds) correlation times as the temperature increases, suggesting
that the loop structure has become disordered.
PMID- 9649314
TI - Influence of lipid/peptide hydrophobic mismatch on the thickness of
diacylphosphatidylcholine bilayers. A 2H NMR and ESR study using designed
transmembrane alpha-helical peptides and gramicidin A.
AB - We have investigated the effect of a series of hydrophobic polypeptides (WALP
peptides) on the mean hydrophobic thickness of (chain-perdeuterated)
phosphatidylcholines (PCs) with different acyl chain length, using 2H NMR and ESR
techniques. The WALP peptides are uncharged and consist of a sequence with
variable length of alternating leucine and alanine, flanked on both sides by two
tryptophans, and with the N- and C-termini blocked, e.g., FmAW2(LA)nW2AEtn. 2H
NMR measurements showed that the shortest peptide with a total length of 16 amino
acids (WALP16) causes an increase of 0.6 A in bilayer thickness in di-C12-PC, a
smaller increase in di-C14-PC, no effect in di-C16-PC, and a decrease of 0.4 A in
di-C18-PC, which was the largest decrease observed in any of the peptide/lipid
systems. The longest peptide, WALP19, in di-C12-PC caused the largest increase in
thickness of the series (+1.4 A), which decreased again for longer lipids toward
di-C18-PC, in which no effect was noticed. WALP17 displayed an influence
intermediate between that of WALP16 and WALP19. Altogether, incorporation of the
WALP peptides was found to result in small but very systematic changes in bilayer
thickness and area per lipid molecule, depending on the difference in hydrophobic
length between the peptide and the lipid bilayer in the liquid-crystalline phase.
ESR measurements with spin-labeled lipid probes confirmed this result. Because
thickness is expected to be influenced most at the lipids directly adjacent to
the peptides, also the maximal adaptation of these first-shell lipids was
estimated. The calculation was based on the assumption that there is little or no
aggregation of the WALP peptides, as was supported by ESR, and that lipid
exchange is rapid on the 2H NMR time scale. It was found that even the maximal
possible changes in first-shell lipid length were relatively small and
represented only a partial response to mismatch. The synthetic WALP peptides are
structurally related to the gramicidin channel, which was therefore used for
comparison. In most lipid systems, gramicidin proved to be a stronger perturber
of bilayer thickness than WALP19, although its length should approximate that of
the shorter WALP16. The effects of gramicidin and WALP peptides on bilayer
thickness were evaluated with respect to previous 31P NMR studies on the effects
of these peptides on macroscopic lipid phase behavior. Both approaches indicate
that, in addition to the effective hydrophobic length, also the physical nature
of the peptide surface is a modulator of lipid order.
PMID- 9649315
TI - Effect of N-terminal truncation and solution conditions on chemokine dimer
stability: nuclear magnetic resonance structural analysis of macrophage
inflammatory protein 1 beta mutants.
AB - Chemokines (chemotactic cytokines) are a family of immune system proteins,
several of which have been shown to block human immunodeficiency virus (HIV)
infection in various cell types. While the solved structures of most chemokines
reveal protein dimers, evidence has accumulated for the biological activity of
individual chemokine monomers, and a debate has arisen regarding the biological
role of the chemokine dimer. Concurrent with this debate, several N-terminal
truncations and modifications in the CC subfamily of chemokines have been shown
to have functional significance, in many cases antagonizing their respective
receptors and in some cases retaining the ability to block HIV entry to the cell.
As the dimer interface of CC chemokines is located at their N-terminus, a
structural study of N-terminally truncated chemokines will address the effect
that this type of mutation has on the dimer-monomer equilibrium. We have studied
the structural consequences of N-terminal truncation in macrophage inflammatory
protein 1 beta (MIP-1 beta), a CC chemokine that has been shown to block HIV
infection. Examination of nuclear magnetic resonance (NMR) spectra of a series of
N-terminally truncated MIP-1 beta variants reveals that these proteins possess a
range of ability to dimerize. A mutant beginning at amino acid Asp6 [termed
MIP(6)] has near wild-type dimer properties, while further truncation results in
weakened dimer affinity. The mutant MIP(9) (beginning with amino acid Thr9) has
been found to exist solely as a folded monomer. Relaxation measurements yield a
rotational correlation time of 8.6 +/- 0.1 ns for wild-type MIP-1 beta and 4.5 +/
0.1 ns for the MIP(9) mutant, consistent with a wild-type dimer and a fully
monomeric MIP(9) variant. The presence of physiological salt concentration
drastically changes the monomer-dimer equilibrium for both wild-type and most
mutant proteins, heavily favoring the dimeric form of the protein. These results
have implications for structure-function analysis of existing chemokine mutants
as well as for the larger debate regarding the biological existence and activity
of the chemokine dimer.
PMID- 9649316
TI - Contribution of hydrogen bonds to the conformational stability of human lysozyme:
calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants.
AB - The contribution of hydrogen bonds to the conformational stability of human
lysozyme was investigated by the combination of calorimetric and X-ray analyses
of six Tyr --> Phe mutants. Unfolding Delta G and unfolding Delta H values of the
Tyr --> Phe mutant proteins were changed by from +0.3 to -4.0 kJ/mol and from 0
to -16 kJ/mol, respectively, compared to those of the wild-type protein. The net
contribution of a hydrogen bond at a specific site to stability (Delta Gwild/HB),
considering factors affected by substitutions, was evaluated on the basis of X
ray structures of the mutant proteins. In the present study, one of six mutant
proteins was suitable for evaluating the strength of the hydrogen bond. Delta
Gwild/HB for the intramolecular hydrogen bond at Tyr124 was evaluated to be 7.5
kJ/mol. Results of the analysis of other mutants also suggest that hydrogen bonds
of the hydroxyl group of Tyr, including the hydrogen bond with a water molecule,
contribute to the stabilization of the human lysozyme.
PMID- 9649317
TI - Regulation of the expression or recruitment of components of the DNA synthesome
by poly(ADP-ribose) polymerase.
AB - Poly(ADP-ribose) polymerase (PARP) is a component of the multiprotein DNA
replication complex (MRC, DNA synthesome) that catalyzes replication of viral DNA
in vitro. PARP poly(ADP-ribosyl)ates 15 of the approximately 40 proteins of the
MRC, including DNA polymerase alpha (DNA pol alpha), DNA topoisomerase I (topo
I), and proliferating-cell nuclear antigen (PCNA). Although about equal amounts
of MRC-complexed and free forms of PCNA were detected by immunoblot analysis of
HeLa cell extracts, only the complexed form was poly(ADP-ribosyl)ated, suggesting
that poly(ADP-ribosyl)ation of PCNA may regulate its function within the MRC. NAD
inhibited the activity of DNA pol delta in the MRC in a dose-dependent manner,
whereas the PARP inhibitor, 3-AB, reversed this inhibitory effect. The roles of
PARP in modulating the composition and enzyme activities of the DNA synthesome
were further investigated by characterizing the complex purified from 3T3-L1
cells before and 24 h after induction of a round of DNA replication required for
differentiation of these cells; at the latter time point, approximately 95% of
the cells are in S phase and exhibit a transient peak of PARP expression. The MRC
was also purified from similarly treated 3T3-L1 cells depleted of PARP by
antisense RNA expression; these cells do not undergo DNA replication nor terminal
differentiation. Both PARP protein and activity and essentially all of the DNA
pol alpha and delta activities exclusively cosedimented with the MRC fractions
from S phase control cells, and were not detected in the MRC fractions from PARP
antisense or uninduced control cells. Immunoblot analysis further revealed that,
although PCNA and topo I were present in total extracts from both control and
PARP-antisense cells, they were present in the MRC fraction only from induced
control cells, indicating that PARP may play a role in their assembly into an
active DNA synthesome. In contrast, expression of DNA pol alpha, DNA primase, and
RPA was down-regulated in PARP-antisense cells, suggesting that PARP may be
involved in the expression of these proteins. Depletion of PARP also prevented
induction of the expression of the transcription factor E2F-1, which positively
regulates transcription of the DNA pol alpha and PCNA genes; thus, PARP may be
necessary for expression of these genes when quiescent cells are stimulated to
proliferate.
PMID- 9649318
TI - Chromium(III) decreases the fidelity of human DNA polymerase beta.
AB - Certain particulate compounds of hexavalent chromium are well-known occupational
and environmental human carcinogens. Hexavalent chromium primarily enters the
cells and undergoes metabolic reduction; however, the ultimate trivalent
oxidation state of chromium, Cr(III), predominates within the cell. DNA-bound
Cr(III) has been previously shown to decrease the fidelity of replication in the
M13 phage mutation assay. This study was done to understand how Cr(III), in the
presence of physiological concentrations of magnesium, affects the kinetic
parameters of steady-state DNA synthesis in vitro across site-specific O6
methylguanine (m6dG) residues by DNA polymerase beta (pol beta). Cr(III) binds to
the short oligomer templates in a dose-dependent manner and stimulates the
activity of pol beta. Cr(III) stimulates the mutagenic incorporation of dTTP
opposite m6dG more than the nonmutagenic incorporation of dCTP, and thereby
Cr(III) further decreases the fidelity of DNA synthesis across m6dG by pol beta.
In contrast, Cr(III) does not affect the fidelity of DNA synthesis across the
normal template base, dG. Both the enhanced activity and the mutagenic lesion
bypass in the presence of Cr(III) may be associated with Cr(III)-dependent
stimulation of pol beta binding to DNA as reported here. This study shows some of
the mechanisms by which mutagenic chromium affects DNA synthesis.
PMID- 9649319
TI - Antisense binding enhanced by tertiary interactions: binding of phosphorothioate
and N3'-->P5' phosphoramidate hexanucleotides to the catalytic core of a group I
ribozyme from the mammalian pathogen Pneumocystis carinii.
AB - Pneumocystis carinii is the most common lethal opportunistic pathogen infecting
Acquired Immune Deficiency Syndrome (AIDS) patients, and more effective
therapeutics for it are needed. P. carinii, but not humans, contain RNA self
splicing group I introns, so these functionally important RNAs are potential anti
fungal targets. In vitro, d(ATGACT), which mimics the 3' end of the 5' exon of a
conserved ribosomal RNA group I intron from mouse-derived Pneumocystis carinii
binds to a ribozyme that is a truncated form of this intron. The binding is about
30,000 times tighter than expected for simple base-pairing because binding is
enhanced by tertiary interactions. Here we report the effects of modifying the
phosphodiester backbone of d(ATGACT) with phosphorothioate and of d(ATGAC)rU with
N3'-->P5' phosphoramidate linkages. The enhancement of binding by tertiary
interactions is not substantially decreased, and in some cases is increased when
single Rp and Sp phosphorothioate substitutions are made, although overall
binding is weaker by up to 6-fold. A mixture of 5' exon mimic isomers that each
contain five phosphorothioate linkages binds to the ribozyme at least 14-fold
less tightly than the corresponding phosphodiester mimic. In contrast, the 5'
exon mimic with five internal N3'-->P5' phosphoramidate linkages binds 4-fold
more tightly than d(ATGAC)rU. This increased binding is largely due to more
favorable base-pairing, but tertiary interactions still enhance binding by more
than 2, 000-fold. These results indicate that chemically modified, nuclease
stable 5' exon mimics can act as antisense agents with binding enhanced by
tertiary interactions (BETI). This strategy permits design of short antisense
agents with high specificity.
PMID- 9649320
TI - Circular substrates of the hammerhead ribozyme shift the internal equilibrium
further toward cleavage.
AB - To test whether the Y-shaped conformation of the hammerhead ribozyme is
maintained throughout the catalytic pathway, the cleavage properties of circular
substrates which bind the ribozyme through helices I and II were determined.
Constraining the position of helices I and II in this manner did not
significantly alter the rate constant for cleavage, consistent with no large
rearrangement of the helices occurring during catalysis. Unexpectedly, the
"internal" equilibrium between the cleavage and ligation reactions for the
circular hammerheads was shifted further toward cleavage. This effect was due to
the rate of ligation of the circular substrate being slower than the
corresponding linear substrate. The temperature dependence of the internal
equilibrium of the circular substrate revealed that although restricting the
flexibility of the hammerhead reduced the favorable entropy change associated
with cleavage as expected, the unfavorable enthalpy change was reduced as well,
resulting in greater overall cleavage.
PMID- 9649321
TI - Shiga toxin attacks bacterial ribosomes as effectively as eucaryotic ribosomes.
AB - Several pathogenic bacteria, including Shigelladysenteriae and certain strains of
Escherichia coli, produce potent class 2 ribosome inhibiting proteins (RIPs)
termed Shiga toxins (Stx). The toxins are bipartite molecules composed of a
single A chain (StxA) noncovalently associated with a pentamer of receptor
binding B subunits (StxB). StxA and Stx1A from E. coli are protoxins. Proteolysis
generates an A1 enzyme (28 kDa) and an A2 fragment (3 kDa), which remain bound,
inactivating the enzyme, until a disulfide bond linking them is reduced. Efforts
to express active recombinant Stx1A1 in the cytoplasm of E. coli were very
difficult and led to the hypothesis that Stx1A1 is toxic to E. coli. We created
the gene for a His-tagged Stx1A1 (cStx1A1) and expressed it in E. coli from a
tightly controlled expression vector. About 1-2 mg of protein can be purified in
a one-step isolation from 1 L of culture. cStx1A1, RTA, and PAP exhibited similar
high toxicity against the Artemia ribosomes with IC50 values near 1 nM.
Surprisingly, Stx1A1 had an IC50 of 0.8 nM against E. coli ribosomes, about the
same as it had for Artemia ribosomes. This is about 250 times more active than
PAP against bacterial targets, making Stx1A1 the most powerful RIP toxin
presently known against E. coli ribosomes.
PMID- 9649322
TI - Differential effects of camptothecin derivatives on topoisomerase I-mediated DNA
structure modification.
AB - The effects of eleven camptothecin derivatives on calf thymus topoisomerase I
mediated cleavage of synthetic DNA duplex have revealed that the A ring of
camptothecin is very important for its biochemical activity. Depending on the
type, number, and location of substituents, highly active or inactive analogues
were obtained. The persistence of CPT-induced topoisomerase I-DNA covalent binary
complexes was investigated by using as substrates DNA containing several good
topoisomerase I cleavage sites, or else a synthetic DNA duplex of defined
structure with a single high-efficiency cleavage site. The ligation kinetics at a
given topoisomerase I cleavage site were sometimes quite different in the
presence of CPT derivatives whose structures were closely related. Even in the
presence of a single CPT analogue, topoisomerase I-DNA covalent binary complexes
underwent ligation with different kinetics, presumably reflecting a dependence on
DNA sequences flanking the individual topoisomerase I cleavage sites. Individual
camptothecin derivatives also exhibited a spectrum of inhibitory potentials in
blocking the topoisomerase I-mediated rearrangement of branched, nicked, and
gapped DNA duplex substrates; in some cases the potencies of inhibition observed
in these assays for individual camptothecin analogues were quite different than
those determined for stabilization of the unmodified DNA-topoisomerase I binary
complex.
PMID- 9649323
TI - The protein component of Bacillus subtilis ribonuclease P increases catalytic
efficiency by enhancing interactions with the 5' leader sequence of pre-tRNAAsp.
AB - Ribonuclease P (RNase P) is a ribonucleoprotein complex that catalyzes the
formation of the mature 5' end of tRNA. To investigate the role of the protein
component in enhancing the affinity of Bacillus subtilis RNase P for substrate
(Kurz, J. C., Niranjanakumari, S., Fierke, C. A. (1998) Biochemistry 37, 2393),
the kinetics and thermodynamics of binding and cleavage were analyzed for pre
tRNAAsp substrates containing 5' leader sequences of varying lengths (1-33
nucleotides). These data demonstrate that the cleavage rate constant catalyzed by
the holoenzyme is not dependent on the leader length; however, the association
rate constant for substrate binding to holoenzyme increases as the length of the
leader increases, and this is reflected in enhanced substrate affinity of up to 4
kcal/mol. In particular, the protein component of RNase P stabilizes interactions
with nucleotides at -2 and -5 in the 5' leader sequence of the pre-tRNA
substrate. A 1 nucleotide leader decreases substrate affinity >/=15-fold compared
to tRNAAsp due to ground-state destabilization of the enzyme-substrate complex.
This destabilization is overcome by increasing the length of the leader to 2
nucleotides due to P RNA-pre-tRNA contacts that are stabilized by the P protein.
The affinity of RNase P holoenzyme (but not RNA alone) for pre-tRNAAsp is further
enhanced with a substrate containing a 5 nucleotide leader. These data indicate
that novel direct or indirect interactions occur between the 5' leader sequence
of pre-tRNAAsp and the protein component of RNase P.
PMID- 9649324
TI - Hairpin-forming peptide nucleic acid oligomers.
AB - A series of partially self-complementary peptide nucleic acid (PNA) oligomers was
prepared. Examination of their melting behavior, circular dichroism spectra, and
fluorescence properties reveals that these PNA oligomers exist as stem-loop
("hairpin") structures. Fluorescence is readily observed in hairpins containing a
covalently linked, emissive acridine derivative which is, at least partially,
intercalated in the duplex region of the PNA hairpin. The acridine fluorescence
is quenched when an anthraquinone derivative is covalently attached to the PNA so
that it is bound near the acridine in the hairpin structure. Acridine
fluorescence is restored in hairpins containing both the anthraquinone and the
acridine by increasing the temperature and melting the structure to its linear
form or by opening the hairpin through formation of a hybrid duplex with
complementary DNA. The latter process may form the basis for development of
selective and sensitive DNA assays.
PMID- 9649325
TI - Influence of hairpins on template reannealing at trinucleotide repeat duplexes: a
model for slipped DNA.
AB - Hairpin stabilization of polymerase slippage has been proposed as part of the
mechanism for large-scale expansion of CG-rich (CNG, where N = A, T, G, or C)
trinucleotide repeats. However, hairpin formation does not entirely account for
why long repeats but not short repeats or palindromes expand. Using ultraviolet
spectroscopic methods, we examine the thermodynamic and kinetic properties of
repeating trinucleotides to evaluate their behavior at a slippage site. We find
that CNG trinucleotide repeats associated with expansion form stable hairpins
whether they are short (with as few as 10 repeats) or long. However, long
repeating stretches exist as single strands up to 2 orders of magnitude longer
than sequences with either short repeats or random DNA. Thus, long hairpins have
long lifetimes even in the presence of their complementary strands and inhibit
duplex reannealing at a slippage site. The kinetic properties explain why
expansion occurs with high frequency at long repeats but not at short repeats or
palindromes.
PMID- 9649326
TI - Nearest-neighbor thermodynamics of internal A.C mismatches in DNA: sequence
dependence and pH effects.
AB - Thermodynamics of 27 oligonucleotides with internal A.C mismatches at two
different pHs were determined from UV absorbance versus temperature melting
profiles. The data were combined with four literature values and used to derive
nearest-neighbor parameters for all 16 trimer sequences with internal A.C
mismatches at pH 7.0 and 5. 0. The results indicate that the contribution of
single A.C mismatches to duplex stability is strongly dependent on the solution
pH and the nearest-neighbor context. On average, the protonation of an internal
A.C mismatch stabilizes the duplex by 1.39 kcal/mol for DeltaG degrees37 and 7.0
degreesC for the TM. The nearest-neighbor parameters predict DeltaG degrees37,
DeltaH degrees, DeltaS degrees, and TM of oligonucleotides presented in this
study with average deviations of 6.3%, 11.0%, 12.2%, and 1.8 degreesC,
respectively, at pH 7.0 and 4.7%, 5.9%, 6.1%, and 1.3 degreesC, respectively, at
pH 5. 0. At pH 7.0, the contribution of single A.C mismatches to helix stability
ranges from 2.25 kcal/mol for TCA/AAT to 1.22 kcal/mol for GCG/CAC. At pH 5.0,
however, the contribution of A+.C mismatches ranges from 1.09 kcal/mol for
TCT/AAA to -0.43 kcal/mol for GCC/CAG. Implications of the results for
replication fidelity and mismatch repair are discussed.
PMID- 9649327
TI - Fourier transform infrared evidence against Asp beta 99 protonation in
hemoglobin: nature of the Tyr alpha 42-Asp beta 99 quaternary H-bond.
AB - The Tyr alpha 42-Asp beta 99 intersubunit H-bond stabilizes the T quaternary
structure in hemoglobin (Hb) tetramers. We had proposed that Tyr alpha 42 acts as
an acceptor in this H-bond, because the tyrosine Y8a/8b and Y7a' UVRR
(ultraviolet resonance Raman) bands shift in directions opposite to those
expected if tyrosine is an H-bond donor. If Asp beta 99 is the H-bond donor, then
it must be protonated in the T state, and would be a previously unrecognized
contributor to the Bohr effect. This implication was strengthened by the
discovery that an R-minus-T difference FTIR (Fourier transform infrared) band at
1693 cm-1, which might be a signal from protonated carboxylate, is missing in Hb
Kempsey, a mutant in which Asp beta 99 is replaced by Asn. However, we now find
that this FTIR signal is insensitive to 13C-labeling of the aspartate residues in
Hb, and cannot arise from protonated Asp beta 99. There are no other difference
signals in the 1700 cm-1 region at a sensitivity of one COOH group. We conclude
that Asp beta 99 is not protonated, and that the anomalous UVRR shifts must arise
from compensating polarization of the Tyr alpha 42 OH. Candidates for this
compensation are the H-bond donated by the Asp beta 94 backbone NH, and the
nearby positive charge of Arg beta 40.
PMID- 9649328
TI - Investigation of CO binding and release from Mo-nitrogenase during catalytic
turnover.
AB - During enzymatic turnover in the presence of CO, Mo-nitrogenase has been shown to
generate two different EPR signals termed lo-CO (PCO = 0.08 atm) and hi-CO (PCO =
0.5 atm). When the formation of hi-CO is monitored under the conditions of very
low electron flux, a 2 min lag is observed prior to the initial detection of the
signal followed by a near-linear rate of formation during which the S = 3/2
cofactor signal exhibits similar decay kinetics. Increasing the electron flux
produces a significant increase in the rate of both the formation of hi-CO and
the decay of the S = 3/2 cofactor. These results are interpreted in terms of a
state of the enzyme (redox or structural) generated only during turnover which is
needed to initially bind CO to the cofactor. Under high electron flux conditions,
new EPR inflections are observed at g = 5.78, 5.15 and g = 1.95, 1.81 and
tentatively assigned to S = 3/2 and 1/2 states of the CO-bound cofactor and 1
equiv of oxidized P cluster, respectively. Sudden removal of CO from the
environment results in the slow decay (>10 min) of both the hi-CO signal and CO
inhibition of acetylene reduction activity. The use of ethylene glycol to quench
enzymatic activity strongly inhibits the decay of hi-CO (in the presence of CO)
and the subsequent decay of lo-CO (after removal of CO) but does not prevent the
reversible interconversion hi-CO left and right arrow lo-CO + CO.
PMID- 9649329
TI - Simulation of S2-state multiline EPR signal in oriented photosystem II membranes:
structural implications for the manganese cluster in an oxygen-evolving complex.
AB - High-quality angular-dependent spectra of multiline electron paramagnetic
resonance (EPR) signals from the S2-state Mn cluster in a photosynthetic oxygen
evolving complex (OEC) were obtained for partially oriented photosystem (PS) II
membranes, and the magnetic structure of the Mn cluster has been studied by
simulation analysis. The angular-dependent multiline spectra were simulated by
taking into account the anisotropic properties of both hyperfine tensors of
intrinsic Mn ions and g-tensor of the cluster in a tetranuclear model. The best
fit parameters for the simulation indicate that (a) the oxidation state of the S2
state Mn cluster is Mn(III, IV, IV, IV), (b) the electronic orbital configuration
of the Mn(III) ion is (dpi)3[dz2(sigma))]1, (c) the effective g-tensor of the Mn
cluster and the hyperfine tensor of the Mn(III) ion are axially symmetric, and
their principal z-axes are nearly collinear each other, and (d) the z-axis of the
dz2 orbital of the Mn(III) ion and the normal of the thylakoid membrane are at an
angle of 50.1 +/- 1.8 degrees. The results are compatible with those of the
oriented XAFS study [Mukerji, I., et al. (1994) Biochemistry 33, 9712-9721], and
indicate that the O-O vector of the putative di-mu-oxo bridged Mn(III)-Mn(IV)
dimer unit in the Mn cluster tilts by 43-56 degrees with respect to the normal of
thylakoid membrane. A model of the arrangement of the di-mu-oxo bridged Mn(III)
Mn(IV) unit with respect to the thylakoid membrane is proposed.
PMID- 9649330
TI - Temperature dependence of forward and reverse electron transfer from A1-, the
reduced secondary electron acceptor in photosystem I.
AB - Electron-transfer reactions following the formation of P700(+)A1- have been
studied in isolated Photosystem I complexes from Synechococcus elongatus between
300 and 5 K by flash absorption spectroscopy. (1) In the range from 300 to 200 K,
A1- is reoxidized by electron transfer to the iron-sulfur cluster FX. The rate
slows down with decreasing temperature, corresponding to an activation energy of
220 +/- 20 meV in this temperature range. Analyzing the temperature dependence of
the rate in terms of nonadiabatic electron-transfer theory, one obtains a
reorganization energy of about 1 eV and an edge-to-edge distance between A1 and
FX of about 8 A assuming the same distance dependence of the electron-transfer
rate as in purple bacterial reaction centers. (2) At temperatures below 150 K,
different fractions of PS I complexes attributed to frozen conformational
substates can be distinguished. A detailed analysis at 77 K gave the following
results: (a) In about 45%, flash-induced electron transfer is limited to the
formation and decay of the secondary pair P700(+)A1-. The charge recombination
occurs with a t1/2 of about 170 micros. (b) In about 20%, the state P700(+)FX- is
formed and recombines with complex kinetics (t1/2 = 5-100 ms). (c) In about 35%,
irreversible formation of P700(+)FA- or P700(+)FB- is possible. (3) The
transition from efficient forward electron transfer at higher temperatures to
heterogeneous photochemistry at low temperatures has been investigated in
different glass-forming solvents. The yield of forward electron transfer to the
iron-sulfur clusters decreases in a narrow temperature interval. The temperature
of the half-maximal effect varies between different solvents and appears to be
correlated with their liquid to glass transition. It is proposed that
reorganization processes in the surroundings of the reactants which are required
for the stabilization of the charge-separated state become arrested near the
glass transition. This freezing of protein motions and/or solvent reorganization
may affect electron-transfer reactions through changes in the free-energy gap and
the reorganization energy. (4) The rate of charge recombination between P700(+)
and A1- increases slightly (about 1.5-fold) when the temperature is decreased
from 300 to 5 K. This charge recombination characterized by a large driving force
is much less influenced by the solvent properties than the forward electron
transfer steps from A1- to FX and FA/B.
PMID- 9649331
TI - Fusion between retinal rod outer segment membranes and model membranes: a role
for photoreceptor peripherin/rds.
AB - Peripherin/rds plays an essential role in the maintenance of photoreceptor rod
cell disk membrane structure. The purification of this protein to homogeneity
[Boesze-Battaglia, K., et al. (1997) Biochemistry 36, 6835-6846] has allowed us
to characterize the functional role of peripherin/rds in the maintenance of rod
outer segment (ROS) membrane fusion processes. Utilizing a cell-free fusion assay
system, we report that the fusion of R18-labeled ROS plasma membrane (R18-PM)
with disk membranes or peripherin/rds-enriched large unilammellar vesicles (LUVs)
is inhibited upon trypsinolysis of peripherin/rds. To understand this phenomenon,
we tested the ability of a series of overlapping synthetic C-terminal
peripherin/rds peptides to mediate model membrane fusion. Within the 63 amino
acid long region of the C-terminus, we identified a minimal 15 residue long amino
acid sequence (PP-5), which is necessary to promote membrane fusion. PP-5 was
able to inhibit R18-PM disk membrane fusion and promoted ANTS/DPX contents mixing
in a pure vesicle system. This peptide (PP-5) promoted calcium-induced vesicle
aggregation of phosphatidylethanolamine:phosphatidylserine LUVs. FTIR analysis
confirmed the structural prediction of this peptide as alpha-helical. When
modeled as an alpha-helix, this peptide is amphiphilic with a hydrophobicity
index of 0.75 and a hydrophobic moment of 0.59. PP-5 has substantial biochemical
and functional homology with other well-characterized membrane fusion proteins.
These results demonstrate the necessity for peripherin/rds in ROS membrane
fusion, specifically the requirement for an intact C-terminal region of this
protein.
PMID- 9649332
TI - Depth profiles of pulmonary surfactant protein B in phosphatidylcholine bilayers,
studied by fluorescence and electron spin resonance spectroscopy.
AB - Pulmonary surfactant-associated protein B (SP-B) has been isolated from porcine
lungs and reconstituted in bilayers of dipalmitoylphosphatidylcholine (DPPC) or
egg yolk phosphatidylcholine (PC) to characterize the extent of insertion of the
protein into phospholipid bilayers. The parameters for the interaction of SP-B
with DPPC or PC using different reconstitution protocols have been estimated from
the changes induced in the fluorescence emission spectrum of the single protein
tryptophan. All the different reconstituted SP-B-phospholipid preparations
studied had similar Kd values for the binding of the protein to the lipids, on
the order of a few micromolar. The depth of penetration of SP-B into phospholipid
bilayers has been estimated by the parallax method, which compares the relative
efficiencies of quenching of the protein fluorescence by a shallow or a deeper
spin-labeled phospholipid probe. SP-B tryptophan was found to be located 10-13 A
from the center of bilayers, which is consistent with a superficial location of
SP-B in phosphatidylcholine membranes. Parallax experiments, as well as resonance
energy transfer from SP-B tryptophan to an acceptor probe located in the center
of the bilayer, indicate that there are significant differences in the extent of
insertion of the protein, depending on the method of reconstitution. SP-B
reconstituted from lipid/protein mixtures in organic solvents is inserted more
deeply in PC or DPPC bilayers than the protein reconstituted by addition to
preformed phospholipid vesicles. These differences in the extent of insertion
lead to qualitative and quantitative differences in the effect of the protein on
the mobility of the phospholipid acyl chains, as studied by spin-label electron
spin resonance (ESR) spectroscopy, and could represent different functional
stages in the surfactant cycle.
PMID- 9649333
TI - Nonesterified fatty acids induce transmembrane monovalent cation flux: host-guest
interactions as determinants of fatty acid-induced ion transport.
AB - Nonesterified fatty acids are key intermediates in cellular metabolism whose
intracellular concentration is regulated by multiple anabolic, catabolic, and
oxidative enzymatic cascades. Herein, we demonstrate that fatty acids induce
transmembrane monovalent cation flux with an apparent rate constant kapp = 10(-)4
- 10(-)3 s-1. Fatty acid-induced cation efflux exploits the ionic association of
the cation with the carboxylate anion of the fatty acid and the subsequent
transmembrane flip-flop of the fatty acid-cation complex. Rates of fatty acid
induced transmembrane cation flux were dependent upon complex host-guest
interactions between the fatty acid-cation complex and the phospholipid
constituents which comprise the membrane bilayer including (1) the degree of
unsaturation of the fatty acid guest and the regiospecificity and
stereospecificity of its olefinic linkages; (2) the phospholipid subclass and
individual molecular species which constitute the host membrane phospholipids;
(3) impedance matching of host and guest hydrophobic characteristics; and (4) the
cholesterol content of the membrane bilayer. Arrhenius analysis demonstrated that
fatty acid-induced K+ efflux was facilitated largely by changes in the entropy of
activation of ion translocation and not the energy of activation. Moreover,
Arrhenius analysis demonstrated that the energy of activation of ion
translocation was phospholipid subclass specific. For example, arachidonic acid
induced cation efflux in membranes comprised of 16:0-18:1 plasmenylcholine
possessed an Ea = 5.3 +/- 0.4 kcal/mol, while that for 16:0-18:1
phosphatidylcholine was 7.2 +/- 0.5 kcal/mol. Electrophysiologic measurements of
planar lipid membranes containing 10 mol % arachidonic acid as a substitutional
impurity confirmed the ability of physiologically relevant amounts of fatty acid
to induce ion translocation with a specific conductance of 2.6 +/- 0.3
microS/cm2. Collectively, these results demonstrate that fatty acids facilitate
transmembrane cation flux by an ion carrier type mechanism and suggest that fatty
acid-mediated ion transport contributes to the leakage current present in many
cell types and thus potentially modulates cellular responsivity during signal
transduction where the intracellular content of fatty acids changes dramatically.
PMID- 9649334
TI - Conformation and lipid binding properties of four peptides derived from the
membrane-binding domain of CTP:phosphocholine cytidylyltransferase.
AB - We are probing the mechanism of the lipid selective membrane interactions of
CTP:phosphocholine cytidylyltransferase (CT). We have proposed that the membrane
binding domain of CT (domain M) consists of a continuous amphipathic alpha-helix
between residues approximately 240-295 [Dunne, S. J., et al. (1996) Biochemistry
35, 11975-11984]. This study examined the secondary structure and membrane
binding properties of synthetic peptides derived from domain M: a 62mer peptide
encompassing the entire domain (Pep62), a 33mer corresponding to the N-terminal
portion (PepNH1), and two 33mers corresponding to the three C-terminal 11mer
repeats, one with the wild-type sequence (Pep33Ser), and one with the three
serines in the nonpolar face substituted with alanine (Pep33Ala). Peptide
secondary structure was analyzed by circular dichroism, and lipid interactions
were analyzed by a direct vesicle binding assay, by effects of lipid vesicles on
peptide tryptophan fluorescence, and by monolayer surface pressure changes. All
peptides bound to vesicles as alpha-helices with selectivity for anionic lipids.
Binding involved intercalation of the peptide tryptophan into the hydrophobic
membrane core. PepNH1, the peptide with the highest positive charge density,
showed strong selectivity for anionic lipids. PepNH1 and Pep33Ser did not bind to
PC vesicles; however, the more hydrophobic peptides, Pep33Ala and Pep62, did bind
to PC vesicles, with apparent partition coefficients for PC that were only
approximately 1 order of magnitude lower than those for PC/PG (1/1). Our results
suggest that the polar serines interrupting the nonpolar face of the amphipathic
helix serve to lower the lipid affinity and thereby enhance selectivity for
anionic lipids. Although diacylglycerol is an activator of the enzyme, none of
the peptides responded differentially to PC/diacylglycerol vesicles versus pure
PC vesicles, suggesting that domain M alone is not sufficient for the enzyme's
response to diacylglycerol. Increases in surface pressure at an air-water
interface indicated that the domain M peptides had strong surface-seeking
tendencies. This supports a binding orientation for domain M parallel to the
membrane surface. Binding of CT peptides to spread lipid monolayers caused
surface pressure reductions, suggesting condensation of lipids in the formation
of lipid-peptide complexes. At low monolayer surface pressures, Pep62 interacted
equally with anionic and zwitterionic phospholipids. This suggests that one
determinant of the selectivity for anionic lipids is the lipid packing density
(area per molecule).
PMID- 9649335
TI - Poly(ADP-ribose) modulates the properties of MARCKS proteins.
AB - In mammalian cells, the formation of DNA strand breaks is accompanied by
synthesis of poly(ADP-ribose). This nucleic acid-like homopolymer may modulate
protein functions by covalent and/or noncovalent interactions. Here we show that
poly(ADP-ribose) binds strongly to the proteins of the myristoylated alanine-rich
C kinase substrate (MARCKS) family, MARCKS and MARCKS-related protein (also
MacMARCKS or F52). MARCKS proteins are myristoylated proteins associated with
membranes and the actin cytoskeleton. As targets for both protein kinase C (PKC)
and calmodulin (CaM), MARCKS proteins are thought to mediate cross-talk between
these two signal transduction pathways. Dot blot assays show that poly(ADP
ribose) binds to MARCKS proteins at the highly basic effector domain. Complex
formation between MARCKS-related protein and CaM as well as phosphorylation of
MARCKS-related protein by the catalytic subunit of PKC are strongly inhibited by
equimolar amounts of poly(ADP-ribose), suggesting a high affinity of poly(ADP
ribose) for MARCKS-related protein. Binding of MARCKS-related protein to
membranes is also inhibited by poly(ADP-ribose). Finally, poly(ADP-ribose)
efficiently reverses the actin-filament bundling activity of a peptide
corresponding to the effector domain and inhibits the formation of actin
filaments in vitro. Our results suggest that MARCKS proteins and actin could be
targets of the poly(ADP-ribose) DNA damage signal pathway.
PMID- 9649336
TI - Evidence for hydrophobic interaction between galanin and the GalR1 galanin
receptor and GalR1-mediated ligand internalization: fluorescent probing with a
fluorescein-galanin.
AB - Galanin is a neuropeptide that activates specific receptors to modulate several
physiological functions including food intake, nociception, and learning and
memory. The molecular nature of the interaction between galanin and its receptors
and the fate of the galanin/receptor complex after the binding event are not
understood. A fluorescein-N-galanin (F-Gal) was generated to measure the
interaction between galanin and rat GalR1 galanin receptor (rGalR1) and rGalR1
mediated ligand internalization using flow cytometry in transfected Chinese
hamster ovary (CHO) cells. Like galanin, F-Gal bound rGalR1 with high affinity
and stimulated intracellular signaling events. Fluorescence quenching by soluble
KI of rGalR1-bound F-Gal revealed a highly protected environment around the
fluorescein, suggesting that the N-terminal portion of galanin, which constitutes
the binding site of galanin for the receptor, binds to a protected hydrophobic
binding pocket within the receptor. Exposure to F-Gal stimulated rapid (t1/2
approximately 10 min) and extensive (78%) internalization of surface F-Gal into
rGalR1/CHO cells at 37 degreesC but not at 0 degreesC. In addition, the
internalization did not occur in parental CHO cells at either 0 or 37 degreesC
and was inhibited by addition of 0.25 M sucrose in the medium, indicating a GalR1
mediated energy-requiring endocytic process. These results revealed a hydrophobic
interaction between galanin and the GalR1 receptor, which is in contrast to those
of other G protein-coupled receptors that mainly require hydrophilic interaction
with their peptide ligands near or outside the plasma membrane surface, and
illustrated that the initial binding interaction is followed by rapid cellular
internalization of the agonist/GalR1 complex.
PMID- 9649337
TI - Progressive decline in the ability of calmodulin isolated from aged brain to
activate the plasma membrane Ca-ATPase.
AB - To identify possible relationships between the loss of calcium homeostasis in
brain associated with aging and alterations in the function of key calcium
regulatory proteins, we have purified calmodulin (CaM) from the brains of Fischer
344 rats of different ages and have assessed age-related alterations in (i) the
secondary and tertiary structure of CaM and (ii) the ability of CaM to activate
one of its target proteins, the plasma membrane (PM) Ca-ATPase. There is a
progressive, age-dependent reduction in the ability of CaM to activate the PM-Ca
ATPase, which correlates with the oxidative modification of multiple methionines
to their corresponding methionine sulfoxides. No other detectable age-related
posttranslational modifications occur in the primary sequence of CaM, suggesting
that the reduced ability of CaM to activate the PM-Ca-ATPase is the result of
methionine oxidation. Corresponding age-related changes in the secondary and
tertiary structure of CaM occur, resulting in alterations in the relative
mobility of CaM on polyacrylamide gels, differences in the intrinsic fluorescence
intensity and solvent accessibility of Tyr99 and Tyr138, and a reduction in the
average alpha-helical content of CaM at 20 degreesC. Shifts in the calcium- and
CaM-dependent activation of the PM-Ca-ATPase are observed for CaM isolated from
senescent brain, which respectively requires larger concentrations of either
calcium or CaM to activate the PM-Ca-ATPase. The observation that the oxidative
modification of CaM during normal biological aging results in a reduced calcium
sensitivity of the PM-Ca-ATPase, a lower affinity between CaM and the PM-Ca
ATPase, and the reduction in the maximal velocity of the PM-Ca-ATPase is
consistent with earlier results that indicate the calcium handling capacity of a
range of tissues including brain, heart, and erythrocytes isolated from aged
animals declines, resulting in both longer calcium transients and elevated basal
levels of intracellular calcium. Thus, the oxidative modification of selected
methionines in CaM may explain aspects of the loss of calcium homeostasis
associated with the aging process.
PMID- 9649338
TI - Cationic residues 53 and 56 control the anion-induced interfacial k*cat
activation of pancreatic phospholipase A2.
AB - Added NaCl or anionic amphiphiles increase the rate of hydrolysis of dispersions
of zwitterionic phospholipid by pancreatic phospholipase A2 (PLA2). Two effects
of the negative charge at the interface have been dissected: enhanced binding of
the enzyme to the interface, and k*cat activation of the enzyme at the interface
[Berg et al. (1997) Biochemistry 36, 14512-14530]. Results reported here show
that the structural basis for the k*cat activation is predominantly through
cationic K53 and K56 in bovine pancreatic PLA2 with the anionic interface. The
maximum rate at saturating diheptanoylphosphatidylcholine micelles, VMapp, for
WT, K56M, and K53M in 4 M NaCl is in the 800-1300 s-1 range. In contrast, VMapp
at 0.1 M NaCl is considerably higher for K56M (400 s-1) and K53M (230 s-1)
compared to the rate with WT (30 s-1) or K56E (45 s-1). The rate of hydrolysis of
anionic dimyristoylphosphatidylmethanol vesicles is virtually the same with all
these mutants (200-300 s-1) and it is not affected by added NaCl. The chemical
step for the hydrolysis of anionic and zwitterionic substrates remains rate
limiting in the presence or absence of added NaCl. A modest (approximately 10
fold) effect of K56M substitution or of added NaCl is seen on the binding of the
enzyme to the interface; however, the binding of the substrate or a substrate
mimic to the active site of the enzyme at the interface is not affected by more
than a factor of 2. Magnitudes of the primary rate and equilibrium parameters at
the zwitterionic and anionic interfaces show that the effect of mutation or of
added NaCl is primarily on k*cat at the zwitterionic interface. These results are
interpreted in terms of a two-state model for the interfacial allosteric
activation, where the enzyme-substrate complex at the zwitterionic interface
becomes catalytically active only after the positive charge on cationic K56 and
K53 has been removed by mutation or neutralized by anionic charges in the
interface.
PMID- 9649339
TI - Effects of single and double mutations in plastocyanin on the rate constant and
activation parameters for the rearrangement gating the electron-transfer reaction
between the triplet state of zinc cytochrome c and cupriplastocyanin.
AB - The unimolecular rate constant for the photoinduced electron-transfer reaction
3Zncyt/pc(II) --> Zncyt+/pc(I) within the electrostatic complex of zinc
cytochrome c and spinach cupriplastocyanin is kF. We report the effects on kF of
the following factors, all at pH 7.0: 12 single mutations on the plastocyanin
surface (Leu12Asn, Leu12Glu, Leu12Lys, Asp42Asn, Asp42Lys, Glu43Asn, Glu59Gln,
Glu59Lys, Glu60Gln, Glu60Lys, Gln88Glu, and Gln88Lys), the double mutation
Glu59Lys/Glu60Gln, temperature (in the range 273.3-302.9 K), and solution
viscosity (in the range 1. 00-116.0 cP) at 283.2 and 293.2 K. We also report the
effects of the plastocyanin mutations on the association constant (Ka) and the
corresponding free energy of association (DeltaGa) with zinc cytochrome c at
298.2 K. Dependence of kF on temperature yielded the activation parameters
DeltaH, DeltaS, and DeltaG. Dependence of kF on solution viscosity yielded the
protein friction and confirmed the DeltaG values determined from the temperature
dependence. The aforementioned intracomplex reaction is not a simple electron
transfer reaction because donor-acceptor electronic coupling (HAB) and
reorganizational energy (lambda), obtained by fitting of the temperature
dependence of kF to the Marcus equation, deviate from the expectations based on
precedents and because kF greatly depends on viscosity. This last dependence and
the fact that certain mutations affect Ka but not kF are two lines of evidence
against the mechanism in which the electron-transfer step is coupled with the
faster, but thermodynamically unfavorable, rearrangement step. The electron
transfer reaction is gated by the slower, and thus rate determining, structural
rearrangement of the diprotein complex; the rate constant kF corresponds to this
rearrangement. Isokinetic correlation of DeltaH and DeltaS parameters and
Coulombic energies of the various configurations of the Zncyt/pc(II) complex
consistently show that the rearrangement is a facile configurational fluctuation
of the associated proteins, qualitatively the same process regardless of the
mutations in plastocyanin. Correlation of kF with the orientation of the
cupriplastocyanin dipole moment indicates that the reactive configuration of the
diprotein complex involves the area near the residue 59, between the upper acidic
cluster and the hydrophobic patch. Kinetic effects and noneffects of plastocyanin
mutations show that the rearrangement from the initial (docking) configuration,
which involves both acidic clusters, to the reactive configuration does not
involve the lower acidic cluster and the hydrophobic patch but involves the upper
acidic cluster and the area near the residue 88.
PMID- 9649340
TI - Spectroscopic and magnetic studies of human ceruloplasmin: identification of a
redox-inactive reduced Type 1 copper site.
AB - Ceruloplasmin is unique among the multicopper oxidases in that in addition to the
usual copper stoichiometry of one Type 1 copper site and a Type 2/Type 3
trinuclear copper cluster, it contains two other Type 1 sites. This assignment of
copper sites, based on copper quantitation, sequence alignment, and
crystallography, is difficult to reconcile with the observed spectroscopy.
Furthermore, some chemical or spectroscopic differences in ceruloplasmin have
been reported depending on the method of purification. We have studied the
resting (as isolated by a fast, one-step procedure) and peroxide-oxidized forms
of human ceruloplasmin. Using a combination of X-ray absorption spectroscopy, a
chemical assay, magnetic susceptibility, electron paramagnetic resonance
spectroscopy, and absorption spectroscopy, we have determined that peroxide
oxidized ceruloplasmin contains one permanently reduced Type 1 site. This site is
shown to have a reduction potential of approximately 1.0 V. Thus, one of the
additional Type 1 sites in ceruloplasmin cannot be catalytically relevant in the
form of the enzyme studied. Furthermore, the resting form of the enzyme contains
an additional reducing equivalent, which is distributed among the remaining five
copper sites as expected from their relative potentials. This may indicate that
the resting form of ceruloplasmin in plasma under aerobic conditions is a four
electron oxidized form, which is consistent with its function in the four
electron reduction of dioxygen to water.
PMID- 9649341
TI - Ro 09-2210 exhibits potent anti-proliferative effects on activated T cells by
selectively blocking MKK activity.
AB - By using high throughput screening of microbial broths, we have identified a
compound, designated Ro 09-2210, which is able to block anti-CD3 induced
peripheral blood T cell activation with an IC50 = 40 nM. Ro 09-2210 was also able
to block antigen-induced IL-2 secretion with an IC50 = 30 nM, but was
considerably less potent at blocking Ca2+ flux stimulated by anti-CD3 treatment.
To determine the mechanism of action of Ro 09-2210, we set up a transient
expression system in Jurkat T cells using a variety of reporter gene constructs
and showed effective inhibition of phorbol ester/ionomycin-induced NF-AT
activation and anti-CD3 induced NF-AT with IC50 = 7.7 and 10 nM, respectively. Ro
09-2210 was also able to inhibit phorbol ester/ionomycin-induced activation of
AP1 with IC50 = <10 nM. We further showed that Ro 09-2210 was unable to inhibit c
jun induced expression of AP1-dependent reporter constructs (IC50 > 500 nM), but
was able to potently inhibit ras-induced AP1 activation (IC50 = 20 nM). This
suggested that Ro 09-2210 was inhibiting an activator of AP-1 which was upstream
of c-jun and downstream of ras signaling. To investigate further, we then
purified a number of different kinases, including PKC, PhK, ZAP-70, ERK, and MEK
1 (a MKK), and showed that Ro 09-2210 was a selective inhibitor of MEK1 in vitro
(IC50 = 59 nM).
PMID- 9649342
TI - Role of important hydrophobic amino acids in the interaction between the
glucocorticoid receptor tau 1-core activation domain and target factors.
AB - In this work, we determined how altered-function mutants affecting hydrophobic
residues within the tau 1-core activation domain of the human glucocorticoid
receptor (GR) influence its physical interaction with different target proteins
of the transcriptional machinery. Screening of putative target proteins showed
that the tau 1-core can interact with the C-terminal part of the CREB-binding
protein (CBP). In addition, the previously identified interactions of the tau 1
core with the TATA-binding protein (TBP) and the Ada2 adaptor protein were
localized to the C- and N-terminal regions of these proteins, respectively. A
panel of mutations within the tau 1-core that either decrease or increase
activation potential was used to probe the interaction of the tau 1-core domain
with TBP, Ada2, and CBP. We found that the pattern of effects caused by the
mutations was similar for each of the interactions and that the effects on
binding generally reflected effects on gene activation potential. Thus, the
predominant effect of the mutations appears to influence a property of the tau 1
core that is common to all three interactions, rather than properties that are
differentially required by each of the target factor interactions, individually.
Such a property could be the ability of the domain to adopt a folded conformation
that is generally necessary for interaction with target factors. We have also
shown that TBP, Ada2, and CBP can interact with both the tau 1-core and the GR
ligand-binding domain, offering a possible mechanism for synergistic interaction
between the tau 1-core and other receptor activation domains. However, other
target proteins (e.g., RIP140, and SRC-1), which interact with the GR C terminus,
did not show significant interactions with the tau 1-core under our conditions.
PMID- 9649343
TI - Thermal denaturation of ribonuclease A characterized by water 17O and 2H magnetic
relaxation dispersion.
AB - Water oxygen-17 and deuteron nuclear magnetic relaxation dispersion (NMRD)
measurements were used to characterize ribonuclease A (RNase A) in the course of
thermal denaturation at pH 2 and 4. The structure and dynamics of the protein
were probed by specific long-lived water molecules, by the short-lived surface
hydration, and by labile side-chain hydrogens. The NMRD data show that native
RNase A contains at least three water molecules with a mean residence time of 8
ns at 27 degreesC and an activation enthalpy of ca. 40 kJ mol-1. These water
molecules are identified with some or all of six ordered water molecules partly
buried in surface pockets in the crystal structure of RNase A. The loss of the
17O dispersion at higher temperatures demonstrates that, in the thermally
denatured protein, these surface pockets are either not present or undergoing
large structural fluctuations on a subnanosecond time scale. The relaxation
dispersion step vanishes monotonically and essentially in concert with the CD
denaturation curves, thus ruling out the existence of equilibrium intermediates
with a substantial amount of non-native and long-lived hydration water. The NMRD
data show that thermally denatured RNase A has a relatively compact but highly
flexible structure. The global solvent exposure and the hydrodynamic volume of
the denatured protein are much less than for maximally unfolded disulfide-intact
RNase A. The NMRD data show that thermal denaturation is accompanied by a large
reduction of the mean-square orientational order parameter of side-chain O-H
bonds, implying that, in the denatured state, these side chains sample a wide
distribution of conformational states on a subnanosecond time scale.
PMID- 9649344
TI - Formulation-related problems associated with intravenous drug delivery.
PMID- 9649345
TI - The impact of stereoisomerism in bioequivalence studies.
PMID- 9649346
TI - Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug
interactions.
AB - Amprenavir (141W94, VX-478, KVX-478) is metabolized primarily by CYP3A4
(cytochrome P450 3A4) in recombinant systems and human liver microsomes (HLM).
The effects of ketoconazole, terfenadine, astemizole, rifampicin, methadone, and
rifabutin upon amprenavir metabolism were examined in vitro using HLM.
Ketoconazole, terfenadine, and astemizole were observed to inhibit amprenavir
depletion, consistent with their known specificity for CYP3A4. The HIV protease
inhibitors, indinavir, saquinavir, ritonavir, and nelfinavir, were included in
incubations containing amprenavir to examine the interactions of HIV protease
inhibitors in vitro. The order of amprenavir metabolism inhibition in human liver
microsomes was observed to be: ritonavir > indinavir > nelfinavir > saquinavir.
The Ki value for amprenavir-mediated inhibition of testosterone hydroxylation in
human liver microsomes was found to be approximately 0.5 microM. Studies suggest
that amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a
much lesser extent than ritonavir. Amprenavir, nelfinavir, and indinavir appear
to inhibit CYP3A4 to a moderate extent, suggesting a selected number of
coadministration restrictions.
PMID- 9649347
TI - Investigation on fouling mechanisms for recombinant human growth hormone sterile
filtration.
AB - During sterile filtration of recombinant human growth hormone solutions, severe
membrane fouling was experienced compared to other protein preparations of
significantly higher molecular weights and concentrations. This phenomenon was
attributed to rhGH aggregation/adsorption occurring in the filter pore. To better
understand this phenomenon, we examined several possible fouling mechanisms: (1)
pore constriction, (2) adsorption due to nonspecific binding between protein and
the membrane, (3) shear-induced adsorption, (4) hydrophobic interface-induced
aggregation/adsorption. The protein solutions were sterily filtered using 0.22 mm
filters, and their filtration fluxes were monitored. Filtration on the capillary
and the noncapillary filters suggested that constraints by pore constriction and
tortuosity played only a limited role. Filtration using filters with different
degrees of protein binding tendency suggested that nonspecific adsorption was
insignificant. The shear stress acting on the protein during filtration was
small. RhGH which was intentionally sheared in a high-speed concentrically
rotating device did not aggravate fouling tendency, suggesting that the shear
induced adsorption might not be the major fouling mechanism. The dynamic light
scattering data showed a trace amount of rhGH aggregates always present in
equilibrium with the hydrophobic (air-water and membrane-water) interface. These
aggregates tended to be adsorbed to the membrane, and more aggregates were
generated presumably due to the equilibrium between aggregates and protein
monomers. This adsorption/aggregation process eventually fouled the membrane.
When the hydrophobic interface was occupied by surfactant molecules, the
equilibration kinetics ceased to generate aggregates, thereby minimizing membrane
fouling. This study clarified the cause of such an unusual fouling phenomenon
upon microfiltration.
PMID- 9649348
TI - Morphine-3-glucuronide has a minor effect on morphine antinociception.
Pharmacodynamic modeling.
AB - The objective of this study was to quantify the influence of morphine-3
glucuronide (M3G) on the morphine antinociceptive effect (ANE) and respiratory
effects in the rat. Three groups of rats were pretreated with either saline or
M3G at two different rates. Morphine infusion of 10 mg/h/kg (group A) or 20
mg/h/kg (group B) was administered to each pretreatment group for 3 h. The ANE
was measured by the electrical stimulation vocalization method, and blood gas
parameters (pCO2, pO2, and pH) were assessed. Independent of pretreatment all
groups displayed a concurrent increase in the ANE. The maximal effect diverged
between pretreatments. Acute tolerance was observed, but no rebound effect was
detected. To characterize the ANE, an effect compartment model and an indirect
response model were selected, both capable of describing the observed features.
In both models incorporation of M3G led to a better explanation of the data. On
the basis of the parameters obtained in the fits, naturally occurring M3G would
reduce the antinociceptive effect during a morphine infusion (plasma
concentration 15 microM) by 15-20%. The exposure of M3G did not significantly
change the respiratory response following the morphine treatment.
PMID- 9649349
TI - Quantitation of tricyclic antidepressant drugs based on the formation of mixed
aggregates with surfactants.
AB - A new approach for the quantitation of drugs, based on the measurement of the
critical micelle concentration of mixed surfactant-drug aggregates, is proposed.
This methodology involves the photometric titration of drugs in an aqueous medium
using a surfactant as titrant. The Coomassie Brilliant Blue G (CBBG) dye,
negatively charged, is used as a photometric probe. The analytical applicability
of this approach is demonstrated by quantifying tricyclic antidepressants (TCAs)
such as imipramine, desimipramine, amitriptylin, and nortriptylin. Aggregates
studied included TCA-sodium dodecyl sulfate (SDS) and TCA-Triton X-100 mixtures.
Because of the opposite charge of TCAs and SDS, which causes strong synergistic
effects in the mixture relative to the properties of their individual components,
this anionic surfactant was selected for the quantitation of TCAs. Pharmaceutical
preparations can be analyzed directly after dissolution of the samples in water
or ethanol. The detection limit achieved for the studied drugs is about 0.12 mg L
1, so the proposed method surpasses existing alternative photometric methods in
sensitivity and features a detection limit similar to fluorimetric methods. The
relative standard deviation for 0.8 mg L-1 of TCA is 2.6%.
PMID- 9649350
TI - Calculation of the dimensions of drug-polymer devices based on diffusion
parameters.
AB - The release kinetics of a polymeric-controlled release device are determined by
its geometry and dimensions. A method to calculate the required size and shape of
diffusion-controlled dosage forms to achieve a particular release profile is
presented. The diffusion parameters are determined for various drugs
(theophylline, diltiazem hydrochloride and caffeine) with thin ethyl cellulose
(EC) films, containing different plasticizers [dibutyl sebacate (DBS) and acetyl
tributyl citrate (ATBC)]. Computer simulations are then used to predict the drug
release kinetics from various dosage forms (e.g. microparticles and cylinders).
The practical benefit of these simulations is to optimize the geometry and
dimensions of a controlled release device without the need of experimental
studies. To verify the theoretical predictions, the release kinetics of
theophylline from EC/ATBC microparticles of different size have also been
determined experimentally. Good agreement is found between theory and experiment,
proving the validity of the presented method.
PMID- 9649351
TI - Racemate and enantiomers of ketoprofen: phase diagram, thermodynamic studies,
skin permeability, and use of chiral permeation enhancers.
AB - The role of intrinsic and extrinsic factors on transport of a chiral drug through
the skin was studied. Ketoprofen (KP) was chosen as a model chiral drug. A
possible relationship between the melting characteristics and the flux values of
S- and RS-KP was investigated. The potential use of chiral enhancers, menthol and
linalool, was also investigated. Thermal analyses were carried out for individual
enantiomers and the racemate of KP. The melting temperature of each enantiomer
was 22 degreesC lower than that of the racemic compound. Peak temperatures from
the melting endotherms were plotted as a function of enantiomeric composition to
give the binary phase diagram. The phase diagram suggested the presence of a
racemic compound, and it was verified by calculations of the liquidus curve in
the dystectic region using reported methods. Powder X-ray diffraction studies
also confirmed that the racemate of KP is a racemic compound. The permeability of
individual enantiomers and the racemate of KP through mice skin was determined in
vitro using side-by-side diffusion cells. Transfer of R- and S-KP from aqueous
solutions of both the racemate and pure enantiomer showed no significant
differences in the rates of permeation, indicating that the rate of transfer of
KP across the mice skin from these solutions was independent of the
stereochemistry of the drug. No evidence of racemization during the transfer
process was observed. The permeation-enhancing ratio of linalool was higher, but
not significant, than that of l-menthol. The predicted ratio of enantiomer to
racemate flux through the skin by the MTMT concept (1. 97) is in close agreement
with the experimentally determined ratio (1.79) across mouse skin.
PMID- 9649352
TI - Pharmacokinetics of (R,S)-Albuterol after aerosol inhalation in healthy adult
volunteers.
AB - The pharmacokinetics of inhaled (R,S)-albuterol following pulmonary absorption
were studied in healthy human subjects. Ten subjects (5 females and 5 males)
inhaled two puffs (180 microg) of albuterol via a metered-dose inhaler and spacer
device. All subjects were nonsmoking and had normal pulmonary function. Charcoal
slurries were ingested to block gastrointestinal absorption of drug. Venous
samples were obtained from each subject at thirteen time points from 0 through 12
h post dose. (R,S)-Albuterol concentration in plasma was measured using a gas
chromatography-mass spectrometry (GC-MS) assay. The plasma concentration-time
profiles conformed to a two-compartment extravascular model with first-order
absorption kinetics. The drug levels reached maximum in 12.6 +/- 2.2 (SD)
minutes, which is in contrast with previous reports that maximum plasma
concentrations occur within 2 to 4 h. The mean peak plasma level was 1469 +/- 410
pg/mL. The mean half-life of distribution was 17.9 +/- 8.2 min. The mean half
life of elimination was 4.4 +/- 1.5 h. Female subjects achieved peak
concentration more rapidly than male subjects (10.4 vs 14.8 min, p = 0.01) and
had a higher mean peak concentration (1778 vs 1159 pg/mL, p = 0.04).
PMID- 9649353
TI - Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver
microsomes: application of the relative activity factor approach.
AB - The relative catalytic activities of CYP2C9 and CYP2C19 in human liver microsomes
has been determined using the approach of relative activity factors (RAFs).
Tolbutamide methylhydroxylation and S-mephenytoin 4'-hydroxylation were used as
measures of CYP2C9 and CYP2C19 activity, respectively. The kinetics of these
reactions were studied in human liver microsomes, in microsomes from human
lymphoblastoid cells, and in insect cells expressing CYP2C9 and CYP2C19. RAFs
were calculated as the ratio of Vmax (reaction velocity at saturating substrate
concentrations) in human liver microsomes of the isoform-specific index reaction
divided by the Vmax of the reaction catalyzed by the cDNA expressed isoform. RAFs
were also determined for SUPERMIX, a commercially available mixture of cDNA
expressed human drug metabolizing CYPs formulated to achieve a balance of enzyme
activities similar to that found in human liver microsomes. Lymphoblast RAF2C9 in
human liver microsomes ranged from 54 to 145 pmol CYP/mg protein (mean value:
87), while a value of 251 pmol CYP/mg protein was obtained for SUPERMIX. Insect
cell RAF2C9 in human liver microsomes ranged from 1.6 to 143 pmol CYP/mg protein
(mean value: 49), while a value of 201 pmol CYP/mg protein was obtained for
SUPERMIX. Both lymphoblast and insect cell RAF2C19 in human liver microsomes
ranged from 4 to 45 pmol CYP/mg protein (mean values: 29 and 28, respectively),
while a value of 29 pmol CYP/mg protein was obtained for SUPERMIX. The nature of
the cDNA expression system used had no effect on the kinetic parameters of CYP2C9
as a tolbutamide methylhydroxylase, or of CYP2C19 as a S-mephenytoin hydroxylase.
However insect cell expressed CYP2C19 (which includes oxidoreductase) had
substantially greater activity as a tolbutamide methylhydroxylase when compared
to lymphoblast expressed CYP2C19. The ratio of mean lymphoblast-determined RAF2C9
to RAF2C19 in human livers was 3.0 (range 1.6-17.9; n = 10), while this ratio for
SUPERMIX was 8.6. The ratio of mean insect cell-determined RAF2C9 to RAF2C19 in
human livers was 1.7 (range 0.04-16.2; n = 10), while this ratio for SUPERMIX was
7.0. Neither ratio is in agreement with the 20:1 ratio of immunoquantified levels
of CYP2C9 and 2C19 in human liver microsomes reported in previous studies.
SUPERMIX may contain catalytically active CYP2C9 in levels higher than those in
human liver microsomes.
PMID- 9649354
TI - Tachycardia alone fails to change the myocardial pharmacokinetics and dynamics of
lidocaine, thiopental, and verapamil after intravenous bolus administration in
sheep.
AB - Previous reports have suggested that tachycardia alone can increase the rate of
myocardial uptake of some drugs. As part of a systematic study of the
determinants of the myocardial uptake and effects of drugs in critical illness,
the effect of tachycardia induced by intracardiac pacing on the myocardial
disposition and effects of lidocaine, verapamil, and thiopental were studied in
chronically instrumented sheep. For each drug, seven sheep received either 100 mg
of lidocaine, 10 mg of verapamil, or 750 mg of thiopental over 2 min in unpaced
and paced (140 beats/min) states on separate occasions and in random order.
Arterial and coronary sinus (effluent from the heart) blood samples were taken at
regular intervals for 30 min, and the maximum rate of change of left ventricular
pressure (LV dP/dtmax) was measured as an index of myocardial contractility.
There were no differences between unpaced and paced studies in the time courses
of arterial and coronary sinus concentrations, or the time-courses of myocardial
contractility and blood flow, after bolus iv injections of these drugs.
Tachycardia alone does not appear to influence the myocardial kinetics or
dynamics of lipophilic drugs that can rapidly diffuse into the heart.
PMID- 9649355
TI - Compositional heterogeneity in parenteral lipid emulsions after sedimentation
field flow fractionation.
AB - This study examines the size and compositional heterogeneity of particles in a
commercial lipid emulsion (Intralipid) before and after equilibration with
penclomedine, a highly lipophilic cytotoxic agent. Emulsions were fractionated by
sedimentation field-flow fractionation (sedFFF), and particle sizes of the
monodisperse fractions were determined by photon correlation spectroscopy. The
triglyceride (TG), phosphatidylcholine (PC), and penclomedine (in drug loaded
emulsions) contents in each fraction were determined by HPLC. The aqueous
entrapped volume within Intralipid was determined to be approximately 10% by size
exclusion chromatography using [3H]mannitol. Thirteen sedFFF fractions collected
from the drug free emulsions yielded particles ranging in size from 154 to 423
nm. Total channel recoveries were 89% and 95% for TG and PC, respectively.
Apparent particle densities varied significantly with size, suggesting
heterogeneity in composition as confirmed by PC/TG mass ratios which varied
dramatically. Computer fits of the distribution profiles suggested populations of
phospholipid vesicles and oil droplets containing excess phospholipid in addition
to classical emulsion droplets. Drug loading induced a significant shift of the
predominant triglyceride containing population to a larger particle size. The
penclomedine distribution profile closely mimicked that of the TG rather than the
PC fraction. These studies suggest the need to consider not only size
distribution but also compositional distribution in characterizing parenteral
emulsions.
PMID- 9649356
TI - In vitro release evaluation of hydrocortisone liquisolid tablets.
AB - The potential of liquisolid systems to improve the dissolution properties of
water-insoluble agents was investigated using hydrocortisone as the model
medication. The in vitro release patterns of this very slightly water-soluble
corticosteroid, formulated in directly compressed tablets and liquisolid
compacts, were studied at different dissolution conditions. The new formulation
technique of liquisolid compacts was used to convert liquid medications such as
solutions or suspensions of hydrocortisone in propylene glycol, a nonvolatile
liquid vehicle, into acceptably flowing and compressible powders by blending with
selective powder excipients. Several liquisolid tablet formulations were prepared
using a new mathematical model to calculate the appropriate quantities of powder
and liquid ingredients required to produce acceptably flowing and compressible
admixtures. Due to their increased wetting properties and surface of drug
available for dissolution, liquisolid compacts demonstrated significantly higher
drug release rates than those of conventionally made, directly compressed tablets
containing micronized hydrocortisone. The in vitro drug dissolution rates of
liquisolid tablets were found to be consistent and independent of the volume of
dissolution medium used, in contrast to the plain tablets which exhibited
declining drug release patterns with decreasing dissolution volumes. It has been
also shown that the fraction of molecularly dispersed drug in the liquid
medication of liquisolid systems is directly proportional to their hydrocortisone
dissolution rates.
PMID- 9649357
TI - On mathematical modeling of dermal and transdermal drug delivery.
AB - This paper deals with two extensions of diffusion models for the drug delivery
process into human skin in order to give a more realistic approach. As one
extension several penetrating substances formulated within a vehicle are
considered for modeling the case of an applied drug and some penetration
modifiers (enhancers and reducers, respectively). A coupling via concentration
dependent diffusivities between the diffusion equations of the involved
substances is used to model the dependencies between them. Furthermore, a moving
boundary problem for the diffusion equation of the drug delivery process is
developed to describe the time-dependent maximum penetration depth of each
penetrant marked by a movingboundary. On this basis a model is developed that can
predict both the concentration profile and the position of the penetration
boundary depending on time. Both concepts are described on a two-dimensional
multilayered domain representing a cross section through human skin. The model
equations are solved by exploiting a suitable numerical discretization method.
PMID- 9649358
TI - How an increase in the carbon chain length of the ester moiety affects the
stability of a homologous series of oxprenolol esters in the presence of
biological enzymes.
AB - beta-Blockers including timolol and propranolol are administered in eye-drops for
the treatment of glaucoma. Due to high incidence of cardiovascular and
respiratory side-effects, their therapeutic value is limited. As a result of poor
ocular bioavailability, many ocular drugs are applied in high concentrations,
which give rise to both ocular and systemic side-effects. Therefore, some methods
have been employed to increase ocular bioavailability such as (a) the development
of drug delivery devices designed to release drugs at controlled rates, (b) the
use of various vehicles that retard precorneal drug loss, and (c) the conversion
of drugs to biologically reversible derivatives (prodrugs) with increased corneal
penetration properties, from which the active drugs are released by enzymatic
hydrolysis. A series of structurally related oxprenolol esters were synthesized
and investigated as potential prodrugs for improved ocular use. The stability of
each ester was studied in phosphate buffer (pH 7.4), also in the presence of (a)
30% human plasma, (b) aqueous humor, and (c) corneal extract at pH 7. 4 and at 37
degreesC. An account is given of how the stability of a homologous series of
oxprenolol esters in the presence of biological enzymes is affected by an
increase in the carbon chain length of the ester moiety.
PMID- 9649359
TI - Determination of absorption characteristics of AG337, a novel thymidylate
synthase inhibitor, using a perfused rat intestinal model.
AB - The purpose of this study was to determine the intestinal absorption
characteristics of AG337, a mechanism-based inhibitor of thymidylate synthase,
using a perfused rat intestinal model. Effects of site, pH, temperature,
concentration, Na+, and inhibitors on the absorption of AG337 were determined,
after the compound was shown to be stable in buffers of various pH, blank
perfusate, and intestinal homogenate. The results indicated that absorption of
AG337 was temperature-, pH-, Na+-, concentration-, and site-dependent. The best
site of absorption is duodenum, where the absorption was 3-10 times (p < 0. 05)
higher than absorption at jejunum, ileum, and colon. Among the four pH's studied,
the best was at pH 6.5 (p < 0.05). Absorption was 80% lower in the absence of
Na+, and 75% lower when the temperature of the perfusate was decreased to 4
degreesC. Permeability of AG337 also decreased about 75% when the concentration
was raised to 100 microM. These results suggest that a nutrient carrier may be
involved in the transport of AG337. To determine the carrier responsible for the
absorption of AG337, its absorption was determined in the presence of various
inhibitors at different concentrations. The results indicated that transport of
AG337 was inhibited significantly (p < 0.01) by 100 microM of adenine,
hypoxanthine, and xanthine. The transport was also inhibited significantly (p <
0.01) by a mixture of 100 microM each of adenine, hypoxanthine, and xanthine, but
not by a mixture of 100 microM each of thymine and uracil. A higher concentration
of hypoxanthine resulted in increased inhibition. In contrast, prototypical
inhibitors of nucleoside transporter, dipyridamole and nitrobenzylthioinosine
(NBMPR), did not significantly decrease the transport of AG337. The results also
showed that absorption of AG337 had a significant nonsaturable component, with a
nonsaturable Pw of 0.8. In conclusion, absorption of AG337 in the rat intestine
has been shown to be mainly via a purine base carrier with a significant
nonsaturable component.
PMID- 9649360
TI - Interactions of griseofulvin with cyclodextrins in solid binary systems.
AB - Griseofulvin/cyclodextrin interactions were investigated in aqueous environment
and in solid state. Two cyclodextrin derivatives (beta-cyclodextrin and 2
hydroxypropyl beta-cyclodextrin) were used to prepare different physical mixtures
and kneaded systems, and the drug/cyclodextrin ratios were 1:1 and 1:2 mol/mol.
Scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential
scanning calorimetry (DSC), thermogravimetry (TG), and X-ray powder
diffractometry were employed to characterize pure substances and their kneaded
counterparts and all of the binary systems. The solubility of griseofulvin was
increased in accord with the quantity of cyclodextrin added. HSM examination
revealed that 2-hydroxypropyl-beta-cyclodextrin was dissolved in the droplets of
melted griseofulvin, but did not show any interactions between melted
griseofulvin and beta-cyclodextrin particles. The presence of griseofulvin
endothermic peak in the DSC curves of all binary systems suggests the absence of
any griseofulvin/cylcodextrin inclusion compound in the solid state. In TG, data
of weight loss owing to the dehydration of cyclodextrins was similar for both
kneaded systems and physical mixtures. X-ray diffraction patterns exhibited the
amorphous nature of 2-hydroxypropyl-beta-cyclodextrin and the crystalline nature
of griseofulvin and binary systems. Griseofulvin dissolution profiles from all
binary systems showed an improvement in drug dissolution, which indicates that an
"in situ" drug/cyclodextrin inclusion compound was formed in the aqueous
dissolution medium.
PMID- 9649361
TI - Plasma-pooling methods to increase throughput for in vivo pharmacokinetic
screening.
PMID- 9649362
TI - Splanchnic clearance and its relationship with drug elimination by the liver and
gastrointestinal tract.
PMID- 9649363
TI - Spiral waves in two-dimensional models of ventricular muscle: formation of a
stationary core.
AB - Previous experimental studies have clearly demonstrated the existence of drifting
and stationary electrical spiral waves in cardiac muscle and their involvement in
cardiac arrhythmias. Here we present results of a study of reentrant excitation
in computer simulations based on a membrane model of the ventricular cell. We
have explored in detail the parameter space of the model, using tools derived
from previous numerical studies in excitation-dynamics models. We have found
appropriate parametric conditions for sustained stable spiral wave dynamics (1 s
of activity or approximately 10 rotations) in simulations of an anisotropic
(ratio in velocity 4:1) cardiac sheet of 2 cm x 2 cm. Initially, we used a model
that reproduced well the characteristics of planar electrical waves exhibited by
thin sheets of sheep ventricular epicardial muscle during rapid pacing at a cycle
length of 300 ms. Under these conditions, the refractory period was 147 ms; the
action potential duration (APD) was 120 ms; the propagation velocity along fibers
was 33 cm/s; and the wavelength along fibers was 4.85 cm. Using cross-field
stimulation in this model, we obtained a stable self-sustaining spiral wave
rotating around an unexcited core of 1.75 mm x 7 mm at a period of 115 ms, which
reproduced well the experimental results. Thus the data demonstrate that stable
spiral wave activity can occur in small cardiac sheets whose wavelength during
planar wave excitation in the longitudinal direction is larger than the size of
the sheet. Analysis of the mechanism of this observation demonstrates that,
during rotating activity, the core exerts a strong electrotonic influence that
effectively abbreviates APD (and thus wavelength) in its immediate surroundings
and is responsible for the stabilization and perpetuation of the activity. We
conclude that appropriate adjustments in the kinetics of the activation front
(i.e., threshold for activation and upstroke velocity of the initiating beat) of
currently available models of the cardiac cell allow accurate reproduction of
experimentally observed self-sustaining spiral wave activity. As such, the
results set the stage for an understanding of functional reentry in terms of
ionic mechanisms.
PMID- 9649364
TI - A simple numerical model of calcium spark formation and detection in cardiac
myocytes.
AB - The elementary events of excitation-contraction coupling in heart muscle are Ca2+
sparks, which arise from one or more ryanodine receptors in the sarcoplasmic
reticulum (SR). Here a simple numerical model is constructed to explore Ca2+
spark formation, detection, and interpretation in cardiac myocytes. This model
includes Ca2+ release, cytosolic diffusion, resequestration by SR Ca2+-ATPases,
and the association and dissociation of Ca2+ with endogenous Ca2+-binding sites
and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic
cytosol reproduce the brightness and the time course of a typical cardiac Ca2+
spark, but underestimate its spatial size (approximately 1.1 micron vs.
approximately 2.0 micron). Back-calculating [Ca2+]i by assuming equilibrium with
indicator fails to provide a good estimate of the free Ca2+ concentration even
when using blur-free fluorescence data. A parameter sensitivity study reveals
that the mobility, kinetics, and concentration of the indicator are essential
determinants of the shape of Ca2+ sparks, whereas the stationary buffers and
pumps are less influential. Using a geometrically more complex version of the
model, we show that the asymmetric shape of Ca2+ sparks is better explained by
anisotropic diffusion of Ca2+ ions and indicator dye rather than by subsarcomeric
inhomogeneities of the Ca2+ buffer and transport system. In addition, we examine
the contribution of off-center confocal sampling to the variance of spark
statistics.
PMID- 9649365
TI - Free energy profiles for H+ conduction along hydrogen-bonded chains of water
molecules.
AB - The molecular mechanism for proton conduction along hydrogen-bonded chains, or
"proton wires," is studied with free energy simulations. The complete transport
of a charge along a proton wire requires two complementary processes: 1)
translocation of an excess proton (propagation of an ionic defect), and 2)
reorientation of the hydrogen-bonded chain (propagation of a bonding defect). The
potential of mean force profile for these two steps is computed in model systems
comprising a single-file chain of nine dissociable and polarizable water
molecules represented by the PM6 model of Stillinger and co-workers. Results of
molecular dynamics simulations with umbrella sampling indicate that the
unprotonated chain is preferably polarized, and that the inversion of its total
dipole moment involves an activation free energy of 8 kcal/mol. In contrast, the
rapid translocation of an excess H+ across a chain extending between two
spherical solvent droplets is an activationless process. These results suggest
that the propagation of a bonding defect constitutes a limiting step for the
passage of several protons along single-file chains of water molecules, whereas
the ionic translocation may be fast enough to occur within the lifetime of
transient hydrogen-bonded water chains in biological membranes.
PMID- 9649366
TI - Structure of the Ca2+ pump of sarcoplasmic reticulum: a view along the lipid
bilayer at 9-A resolution.
AB - We have used multilamellar crystals of the ATP-driven calcium pump from
sarcoplasmic reticulum to address the structural effects of calcium binding to
the enzyme. They are stacks of disk-shaped two-dimensional crystals. A density
map projected along the lipid bilayer was obtained at 9-A resolution by frozen
hydrated electron microscopy. Although only in projection, much more details of
the structure were revealed than previously available, especially in the
transmembrane region. Quantitative comparison was made with the model obtained
from the tubular crystals of this enzyme formed in the absence of calcium.
Unexpectedly large differences in conformation were found, particularly in the
cytoplasmic domain.
PMID- 9649367
TI - Capacitance flickers and pseudoflickers of small granules, measured in the cell
attached configuration.
AB - We have studied exocytosis of single small granules from human neutrophils by
capacitance recordings in the cell-attached configuration. We found that 2.2% of
the exocytotic events were flickers. The flickers always ended with a downward
step. This indicates closing of the fusion pore. During flickering, the fusion
pore conductance remained below 1 nS, and no net membrane transfer was
detectable. After fusion pore expansion beyond 1 nS the pore expanded
irreversibly, leading to rapid full incorporation of the granule/vesicle into the
plasma membrane. Following exocytosis of single granules, a capacitance decrease
directly related to the preceding increase was observed in 7% of the exocytotic
events. This decrease followed immediately after irreversible pore expansion, and
is presumably triggered by full incorporation of the vesicle into the patch
membrane. The capacitance decrease could be interpreted as endocytosis triggered
by exocytosis. However, the gradual decrease could also reflect a decrease in the
"free" patch area following incorporation of an exocytosed vesicle. We conclude
that non-stepwise capacitance changes must be interpreted with caution, since a
number of factors go into determining cell or patch admittance.
PMID- 9649368
TI - Simulating energy flow in biomolecules: application to tuna cytochrome c.
AB - By constructing a continuity equation of energy flow, one can utilize results
from a molecular dynamics simulation to calculate the energy flux or flow in
different parts of a biomolecule. Such calculations can yield useful insights
into the pathways of energy flow in biomolecules. The method was first tested on
a small system of a cluster of 13 argon atoms and then applied to the study of
the pathways of energy flow after a tuna ferrocytochrome c molecule was oxidized.
Initially, energy propagated faster along the direction perpendicular to the heme
plane. This was due to an efficient through-bond mechanism, because the heme iron
in cytochrome c was covalently bonded to a cysteine and a histidine. For the
oxidation of cytochrome c, electrostatic interactions also facilitated a long
range through-space mechanism of energy flow. As a result, polar or charged
groups that were further away from the oxidation site could receive energy
earlier than nonpolar groups closer to the site. Another bridging mechanism
facilitating efficient long-range responses to cytochrome c oxidation involved
the coupling of far-off atoms with atoms that were nearer to, and interacted
directly with, the oxidation site. The different characteristics of these energy
transfer mechanisms defied a simple correlation between the time that the excess
energy of the oxidation site first dissipated to an atom and the distance of the
atom from the oxidation site. For tuna cytochrome c, all of the atoms of the
protein had sensed the effects of the oxidation within approximately 40 fs. For
the length scale of energy transfer considered in this study, the speed of the
energy propagation in the protein was on the order of 10(5) m/s.
PMID- 9649369
TI - Stability of triple-helical poly(dT)-poly(dA)-poly(dT) DNA with counterions.
AB - Structural conformation of triple-helical poly(dT)-poly(dA)-poly(dT) has been a
very controversial issue recently. Earlier investigations, based on fiber
diffraction data and molecular modeling, indicated an A-form conformation with
C'3-endo sugar pucker. On the other hand, Raman, solution infrared spectral, and
NMR studies show a B-form structure with C'2-endo sugars. In accordance with
these experimental results, a theoretical model with B-form, C'2-endo sugars was
proposed in 1993. In the present work we investigate the dynamics and stability
of the two conformations within the effective local field approach applied to the
normal mode calculations for the system. The presence of counterions was
explicitly taken into account. Stable equilibrium positions for the counterions
were calculated by analyzing the normal mode dynamics and free energy of the
system. The breathing modes of the triple helix are shifted to higher frequencies
over those of the double helix by 4-16 cm-1. The characteristic marker band for
the B conformation at 835 cm-1 is split up into two marker bands at 830 and 835
cm-1. A detailed comparison of the normal modes and the free energies indicates
that the B-form structure, with C'2-endo sugar pucker, is more stable than the A
form structure. The normal modes and the corresponding dipole moments are found
to be in close agreement with recent spectroscopic findings.
PMID- 9649370
TI - Computer simulations of de novo designed helical proteins.
AB - In the context of reduced protein models, Monte Carlo simulations of three de
novo designed helical proteins (four-member helical bundle) were performed. At
low temperatures, for all proteins under consideration, protein-like folds having
different topologies were obtained from random starting conformations. These
simulations are consistent with experimental evidence indicating that these de
novo designed proteins have the features of a molten globule state. The results
of Monte Carlo simulations suggest that these molecules adopt four-helix bundle
topologies. They also give insight into the possible mechanism of folding and
association, which occurs in these simulations by on-site assembly of the
helices. The low-temperature conformations of all three sequences have the
features of a molten globule state.
PMID- 9649371
TI - Physical constraints in the synthesis of glycogen that influence its structural
homogeneity: a two-dimensional approach.
AB - Several aspects of glycogen optimization as an efficient fuel storage molecule
have been studied in previous works: the chain length and the branching degree.
These results demonstrated that the values of these variables in the cellular
molecule are those that optimize the structure-function relationship. In the
present work we show that structural homogeneity of the glycogen molecule is also
an optimized variable that plays an important role in its metabolic function.
This problem was studied by means of a two-dimensional approach, which allowed us
to simplify the very complicated structure of glycogen. Our results demonstrate
that there is a molecular size limit that guarantees the structural homogeneity,
beyond which the structure of the molecule degenerates, as many chains do not
grow. This strongly suggests that such a size limit is precisely what the
molecule possesses in the cell.
PMID- 9649372
TI - Assessment of swelling-activated Cl- channels using the halide-sensitive
fluorescent indicator 6-methoxy-N-(3-sulfopropyl)quinolinium.
AB - This study describes a quantitative analysis of the enhancement in anion
permeability through swelling-activated Cl- channels, using the halide-sensitive
fluorescent dye 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). Cultured bovine
corneal endothelial monolayers perfused with NO3- Ringer's were exposed to I-
pulses under isosmotic and, subsequently, hyposmotic conditions. Changes in SPQ
fluorescence due to I- influx were significantly faster under hyposmotic than
under isosmotic conditions. Plasma membrane potential (Em) was -58 and -32 mV
under isosmotic and hyposmotic conditions, respectively. An expression for the
ratio of I- permeability under hyposmotic condition to that under isosmotic
condition (termed enhancement ratio or ER) was derived by combining the Stern
Volmer equation (for modeling SPQ fluorescence quenching by I-) and the Goldman
flux equation (for modeling the electrodiffusive unidirectional I- influx). The
fluorescence values and slopes at the inflection points of the SPQ fluorescence
profile during I- influx, together with Em under isosmotic and hyposmotic
conditions, were used to calculate ER. Based on this approach, endothelial cells
were shown to express swelling-activated Cl- channels with ER = 4.9 when the
hyposmotic shock was 110 +/- 10 mosM. These results illustrate the application of
the SPQ-based method for quantitative characterization of swelling-activated Cl-
channels in monolayers.
PMID- 9649373
TI - Light gradients in spherical photosynthetic vesicles.
AB - Light-gradient photovoltage measurements were performed on EDTA-treated
thylakoids and on osmotically swollen thylakoids (blebs), both of spherical
symmetry but of different sizes. In the case of EDTA vesicles, a negative
polarity (due to the normal light gradient) was observed in the blue range of the
absorption spectrum, and a positive polarity, corresponding to an inverse light
gradient, was observed at lambda = 530 and lambda = 682 nm. The sign of the
photovoltage polarity measured in large blebs (swollen thylakoids) is the same as
that obtained for whole chloroplasts, although differences in the amplitudes are
observed. An approach based on the use of polar coordinates was adapted for a
theoretical description of these membrane systems of spherical symmetry. The
light intensity distribution and the photovoltage in such systems were
calculated. Fits to the photovoltage amplitudes, measured as a function of light
wavelength, made it possible to derive the values of the dielectric constant of
the protein, epsilons = 3, and the refractive index of the photosynthetic
membrane for light propagating perpendicular and parallel to the membrane
surface, nt = 1.42 and nn = 1.60, respectively. The latter two values determine
the birefringence of the biological membrane, Deltan = nn - nt = 0.18.
PMID- 9649374
TI - Structural equilibrium of DNA represented with different force fields.
AB - We have recently indicated preliminary evidence of different equilibrium average
structures with the CHARMM and AMBER force fields in explicit solvent molecular
dynamics simulations on the DNA duplex d(C5T5) . d(A5G5) (Feig, M. and B.M.
Pettitt, 1997, Experiment vs. Force Fields: DNA conformation from molecular
dynamics simulations. J. Phys. Chem. B. (101:7361-7363). This paper presents a
detailed comparison of DNA structure and dynamics for both force fields from
extended simulation times of 10 ns each. Average structures display an A-DNA base
geometry with the CHARMM force field and a base geometry that is intermediate
between A- and B-DNA with the AMBER force field. The backbone assumes B form on
both strands with the AMBER force field, while the CHARMM force field produces
heterogeneous structures with the purine strand in A form and the pyrimidine
strand in dynamical equilibrium between A and B conformations. The results
compare well with experimental data for the cytosine/guanine part but fail to
fully reproduce an overall B conformation in the thymine/adenine tract expected
from crystallographic data, particularly with the CHARMM force field.
Fluctuations between A and B conformations are observed on the nanosecond time
scale in both simulations, particularly with the AMBER force field. Different
dynamical behavior during the first 4 ns indicates that convergence times of
several nanoseconds are necessary to fully establish a dynamical equilibrium in
all structural quantities on the time scale of the simulations presented here.
PMID- 9649375
TI - Diffusion of solvent around biomolecular solutes: a molecular dynamics simulation
study.
AB - Effects of the macromolecular solute on the translational mobility of surrounding
solvent water, and Na+ and Cl- ions are investigated by molecular dynamics (MD)
simulation. Using MD trajectories of myoglobin and d(C5T5) . d(G5A5) DNA decamer
of high quality and length, we determine the average diffusion coefficients for
all solvent species as a function of distance from the closest solute atom. We
examine solvent mobility in the directions parallel and perpendicular to the
solute surface and in proximity to three different classes of solute atoms
(oxygens, nitrogens, and carbons). The nature and the magnitude of the solute
effects on water diffusion appear to be very similar for protein and DNA decamer.
The overall diffusion rate at the interface is lower than in the bulk. The rate
is higher than the average in the direction parallel to the solute surface, and
lower in the direction normal to the surface, up to 15 A away from the solute.
The rate is also lower in the solvation shells of the macromolecules, producing
characteristic depressions in the radial profiles of the diffusion coefficient
that can be correlated with peaks in the corresponding radial distribution
functions. The magnitude of these depressions is small compared to the overall
change in solvent mobility at the interface. Similar features are observed in the
radial profiles of the diffusion coefficient of sodium and chlorine ions as well.
PMID- 9649376
TI - Structure, stability, and thermodynamics of lamellar DNA-lipid complexes.
AB - We develop a statistical thermodynamic model for the phase evolution of DNA
cationic lipid complexes in aqueous solution, as a function of the ratios of
charged to neutral lipid and charged lipid to DNA. The complexes consist of
parallel strands of DNA intercalated in the water layers of lamellar stacks of
mixed lipid bilayers, as determined by recent synchrotron x-ray measurements.
Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA
induced spatial inhomogeneities in the bilayer charge densities are included. The
relevant nonlinear Poisson-Boltzmann equation is solved numerically, including
self-consistent treatment of the boundary conditions at the polarized membrane
surfaces. For a wide range of lipid compositions, the phase evolution is
characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho,
the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d,
is constant; 2) for intermediate rho, including the isoelectric point rho = 1,
all of the lipid and DNA in solution is incorporated into the complex, whose
inter-DNA distance d increases linearly with rho; and 3) for high rho, the
complexes coexist with excess liposomes (whose lipid composition is different
from that in the complex), and their spacing d is nearly, but not completely,
independent of rho. These results can be understood in terms of a simple charging
model that reflects the competition between counterion entropy and inter-DNA (rho
< 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions
are compared with theoretical work by others, and with relevant experiments.
PMID- 9649377
TI - Evidence for a novel bursting mechanism in rodent trigeminal neurons.
AB - We investigated bursting behavior in rodent trigeminal neurons. The essential
mechanisms operating in the biological systems were determined based on testable
predictions of mathematical models. Bursting activity in trigeminal motoneurons
is consistent with a traditional mechanism employing a region of negative slope
resistance in the steady-state current-voltage relationship (Smith, T. G. 1975.
Nature. 253:450-452). However, the bursting dynamics of trigeminal interneurons
is inconsistent with the traditional mechanisms, and is far more effectively
explained by a new model of bursting that exploits the unique stability
properties associated with spike threshold (Baer, S. M., T. Erneux, and J.
Rinzel. 1989. SIAM J. Appl. Math. 49:55-71).
PMID- 9649378
TI - Evidence for multiple open and inactivated states of the hKv1.5 delayed
rectifier.
AB - The kinetic properties of hKv1.5, a Shaker-related cardiac delayed rectifier,
expressed in Ltk- cells were studied. hKv1.5 currents elicited by membrane
depolarizations exhibited a delay followed by biphasic activation. The biphasic
activation remained after 5-s prepulses to membrane potentials between -80 and
30 mV; however, the relative amplitude of the slow component increased as the
prepulse potential approached the threshold of channel activation, suggesting
that the second component did not reflect activation from a hesitant state. The
decay of tail currents at potentials between -80 and -30 mV was adequately
described with a biexponential. The time course of deactivation slowed as the
duration of the depolarizing pulse increased. This was due to a relative increase
in the slowly decaying component, despite similar initial amplitudes reflecting a
similar open probability after 50- and 500-ms prepulses. To further investigate
transitions after the initial activated state, we examined the temperature
dependence of inactivation. The time constants of slow inactivation displayed
little temperature and voltage dependence, but the degree of the inactivation
increased substantially with increased temperature. Recovery from inactivation
proceeded with a biexponential time course, but long prepulses at depolarized
potentials slowed the apparent rate of recovery from inactivation. These data
strongly indicate that hKv1.5 has both multiple open states and multiple
inactivated states.
PMID- 9649379
TI - Electric field-induced functional reductions in the K+ channels mainly resulted
from supramembrane potential-mediated electroconformational changes.
AB - The goal of this study is to distinguish the supramembrane potential difference
induced electroconformational changes from the huge transmembrane current-induced
thermal damages in the delayed rectifier K+ channels. A double Vaseline-gap
voltage clamp was used to deliver shock pulses and to monitor the channel
currents. Three pairs of 4-ms shock pulses were used to mimic the electric shock
by a power-line frequency electric field. Each pair consists of two pulses with
the same magnitude, starting from 350 to 500 mV, but with opposite polarities.
The shock pulse-generated transmembrane ion flux and the responding electric
energy, the Joule heating, consumed in the cell membrane, as well as the effects
on the K+ channel currents, were obtained. Results showed that huge transmembrane
currents are not necessary to cause damages in the K+ channel proteins. In
contrast, reductions in the K+ channel currents are directly related to the field
induced supramembrane potential differences. By a comparison with the shock field
induced Joule heating effects on cell membranes, the field-induced supramembrane
potential difference plays a dominant role in damaging the K+ channels, resulting
in electroconformational changes in the membrane proteins. In contrast, the shock
field-induced huge transmembrane currents, therefore the thermal effects, play a
secondary, trivial role.
PMID- 9649380
TI - Molecular origin of the L-type Ca2+ current of skeletal muscle myotubes
selectively deficient in dihydropyridine receptor beta1a subunit.
AB - The origin of Ibetanull, the Ca2+ current of myotubes from mice lacking the
skeletal dihydropyridine receptor (DHPR) beta1a subunit, was investigated. The
density of Ibetanull was similar to that of Idys, the Ca2+ current of myotubes
from dysgenic mice lacking the skeletal DHPR alpha1S subunit (-0.6 +/- 0.1 and
0.7 +/- 0.1 pA/pF, respectively). However, Ibetanull activated at significantly
more positive potentials. The midpoints of the GCa-V curves were 16.3 +/- 1.1 mV
and 11.7 +/- 1.0 mV for Ibetanull and Idys, respectively. Ibetanull activated
significantly more slowly than Idys. At +30 mV, the activation time constant for
Ibetanull was 26 +/- 3 ms, and that for Idys was 7 +/- 1 ms. The unitary current
of normal L-type and beta1-null Ca2+ channels estimated from the mean variance
relationship at +20 mV in 10 mM external Ca2+ was 22 +/- 4 fA and 43 +/- 7 fA,
respectively. Both values were significantly smaller than the single-channel
current estimated for dysgenic Ca2+ channels, which was 84 +/- 9 fA under the
same conditions. Ibetanull and Idys have different gating and permeation
characteristics, suggesting that the bulk of the DHPR alpha1 subunits underlying
these currents are different. Ibetanull is suggested to originate primarily from
Ca2+ channels with a DHPR alpha1S subunit. Dysgenic Ca2+ channels may be a minor
component of this current. The expression of DHPR alpha1S in beta1-null myotubes
and its absence in dysgenic myotubes was confirmed by immunofluorescence labeling
of cells.
PMID- 9649381
TI - A distinct contribution of the delta subunit to acetylcholine receptor channel
activation revealed by mutations of the M2 segment.
AB - Acetylcholine receptor (AChR) channels with proline (P) mutations in the putative
pore-forming domain (at the 12' position of the M2 segment) were examined at the
single-channel level. For all subunits (alpha, beta, epsilon, and delta), a 12'P
mutation increased the open channel lifetime >5-fold. To facilitate the
estimation of binding and gating rate constants, subunits with 12'P mutations
were co-expressed with alpha subunits having a binding site mutation that slows
channel opening (alphaD200N). In these AChRs, a 12'P mutation in epsilon or beta
slowed the closing rate constant approximately 6-fold but had no effect on either
the channel opening rate constant or the equilibrium dissociation constant for
ACh (Kd). In contrast, a 12'P mutation in delta slowed the channel closing rate
constant only approximately 2-fold and significantly increased both the channel
opening rate constant and the Kd. Pairwise expression of 12'P subunits indicates
that mutations in epsilon and beta act nearly independently, but one in delta
reduces the effect of a homologous mutation in epsilon or beta. The results
suggest that a 12'P mutation in epsilon and beta has mainly local effects,
whereas one in delta has both local and distributed effects that influence both
agonist binding and channel gating.
PMID- 9649382
TI - Anion competition for a volume-regulated current.
AB - We have examined whether the anionic amino acids, glutamate and aspartate,
permeate through the same volume-regulated conductance permeant to Cl- ions. Cell
swelling was initiated in response to establishing a whole-cell configuration in
the presence of a hyposmotic gradient. Volume-regulated anion currents carried by
Cl-, glutamate, or aspartate developed with similar time courses and showed
similar voltage-dependent inactivation. Permeability ratios (Paa/PCl) calculated
from measured reversal potentials were dependent on the mole fraction ratio (MFR)
of the permeant anions ([aa]/([aa] + [Cl-])). MFR was varied from 0.00 to 0.97.
As the fraction of amino acid increased, Paa/PCl decreased. Current amplitude was
similarly dependent on MFR. These results show that the permeation of anionic
amino acids and that of Cl- ions are not independent of each other, indicating
that the ion channel underlying the volume-regulated conductance can be occupied
by more than one ion at a time. Application of Eyring rate theory indicated that
the major barrier to Cl- ion permeation is at the intracellular side of the
membrane, and that the major barrier to amino acid permeation is at the
extracellular side of the membrane. The interactions between these permeant ions
may have a physiological modulatory role in volume regulation through a volume
regulated anion conductance.
PMID- 9649383
TI - Extrapore residues of the S5-S6 loop of domain 2 of the voltage-gated skeletal
muscle sodium channel (rSkM1) contribute to the mu-conotoxin GIIIA binding site.
AB - The tetradomain voltage-gated sodium channels from rat skeletal muscle (rSkM1)
and from human heart (hH1) possess different sensitivities to the 22-amino-acid
peptide toxin, mu-conotoxin GIIIA (mu-CTX). rSkM1 is sensitive (IC50 = 51.4 nM)
whereas hH1 is relatively resistant (IC50 = 5700 nM) to the action of the toxin,
a difference in sensitivity of >100-fold. The affinity of the mu-CTX for a
chimera formed from domain 1 (D1), D2, and D3 from rSkM1and D4 from hH1 (SSSH; S
indicates origin of domain is skeletal muscle and H indicates origin of domain is
heart) was paradoxically increased approximately fourfold relative to that of
rSkM1. The source of D3 is unimportant regarding the difference in the relative
affinity of rSkM1 and hH1 for mu-CTX. Binding of mu-CTX to HSSS was substantially
decreased (IC50 = 1145 nM). Another chimera with a major portion of D2 deriving
form hH1 showed no detectable binding of mu-CTX (IC50 > 10 microM). These data
indicate that D1 and, especially, D2 play crucial roles in forming the mu-CTX
receptor. Charge-neutralizing mutations in D1 and D2 (Asp384, Asp762, and Glu765)
had no effect on toxin binding. However, mutations at a neutral and an anionic
site (residues 728 and 730) in S5-S6/D2 of rSkM1, which are not in the putative
pore region, were found to decrease significantly the mu-CTX affinity with little
effect on tetrodotoxin binding (=1.3-fold increase in affinity). Furthermore,
substitution at Asp730 with cysteine and exposure to Cd2+ or methanethiosulfonate
reagents had no significant effect on sodium currents, consistent with this
residue not contributing to the pore.
PMID- 9649384
TI - The breakdown of cell membranes by electrical and mechanical stress.
AB - We attempted to determine whether mechanical tension and electrical stress couple
to cause membrane breakdown in cells. Using cell-attached patches from HEK293
cells, we estimated the mechanically produced tension from the applied pressure
and geometry of the patch. Voltage pulses of increasing amplitude were applied
until we observed a sudden increase in conductance and capacitance. For pulses of
50 micros duration, breakdown required >0.5 V and was dependent on the tension.
For pulses of 50-100 ms duration, breakdown required 0.2-0.4 V and was
independent of tension. Apparently two physically different processes can lead to
membrane breakdown. We could explain the response to the short, high-voltage
pulses if breakdown occurred in the lipid bilayer. The critical electromechanical
energy per unit area for breakdown by short pulses was approximately 4 dyne/cm,
in agreement with earlier results on bilayers. Our data suggest that, at least in
a patch, the bilayer may hold a significant fraction (approximately 40%) of the
mean tension. To be compatible with the large, nonlytic area changes of patches,
the bilayer appears to be pulled toward the pipette tip, perhaps by hydrophobic
forces wetting membrane proteins bound to the glass. Although breakdown voltages
for long pulses were in agreement with earlier work on algae, the mechanism(s)
for this breakdown remain unclear.
PMID- 9649385
TI - Sulfur distribution in bacteriorhodopsin from multiple wavelength anomalous
diffraction near the sulfur K-edge with synchrotron x-ray radiation.
AB - Bacteriorhodopsin contains nine sulfur atoms from the nine methionine residues.
The distribution of these sulfur atoms in the projected density map was
determined from x-ray diffraction experiments using multiple wavelength anomalous
diffraction (MAD) at the sulfur K-edge (5.02 A) with synchrotron radiation. The
experiments were performed with uniaxial samples of oriented purple membranes at
room temperature and 86% relative humidity. For such samples only the real part
f' (lambda) of the resonant scattering amplitude of sulfur contributes to the
observed scattering intensity. The sulfur density was determined from the
difference in diffraction intensities detected at two wavelengths near the sulfur
K-edge that were approximately 0.004 A apart. The measured change in f' between
these two wavelengths corresponds to 6 electron units. This shows that large
anomalous dispersion effects occur near the sulfur K-edge. The in-plane positions
of the sulfur atoms of Met32, Met56, and Met209 were determined unambiguously.
The difference density from Met20, Met60, Met118, and Met145 is concentrated in
the interior of the seven alpha-helical bundle, overlaps strongly in the
projected density map, and cannot be resolved at the resolution of these
experiments (8.2 A). This method of localizing individual sulfur atoms can be
applied to other two-dimensional protein crystals and is promising in conjunction
with the site-directed introduction of sulfur atoms by the use of cysteine
mutants.
PMID- 9649386
TI - Cholesterol-induced variations in the volume and enthalpy fluctuations of lipid
bilayers.
AB - The sound velocity and density of suspensions of large unilamellar liposomes from
dimyristoylphosphatidylcholine with admixed cholesterol have been measured as a
function of temperature around the chain melting temperature of the phospholipid.
The cholesterol-to-phospholipid molar ratio xc has been varied over a wide range
(0 = xc = 0.5). The temperature dependence of the sound velocity number, of
the apparent specific partial volume of the phospholipid, and of the apparent
specific adiabatic compressibility have been derived from the measured data.
These data are particularly discussed with respect to the volume fluctuations
within the samples. A theoretical relation between the compressibility and the
excess heat capacity of the bilayer system has been derived. Comparison of the
compressibilities (and sound velocity numbers) with heat capacity traces display
the close correlation between these quantities for bilayer systems. This
correlation appears to be very useful as it allows some of the mechanical
properties of membrane systems to be calculated from the specific heat capacity
data and vice versa.
PMID- 9649387
TI - The influence of polymer molecular weight in lamellar gels based on PEG-lipids.
AB - We report x-ray scattering, rheological, and freeze-fracture and polarizing
microscopy studies of a liquid crystalline hydrogel called Lalpha,g. The
hydrogel, found in DMPC, pentanol, water, and PEG-DMPE mixtures, differs from
traditional hydrogels, which require high MW polymer, are disordered, and gel
only at polymer concentrations exceeding an "overlap" concentration. In contrast,
the Lalpha,g uses very low-molecular-weight polymer-lipids (1212, 2689, and 5817
g/mole), shows lamellar order, and requires a lower PEG-DMPE concentration to gel
as water concentration increases. Significantly, the Lalpha,g contains fluid
membranes, unlike Lbeta' gels, which gel via chain ordering. A recent model of
gelation in Lalpha phases predicts that polymer-lipids both promote and stabilize
defects; these defects, resisting shear in all directions, then produce
elasticity. We compare our observations to this model, with particular attention
to the dependence of gelation on the PEG MW used. We also use x-ray lineshape
analysis of scattering from samples spanning the fluid-gel transition to obtain
the elasticity coefficients kappa and B; this analysis demonstrates that although
B in particular depends strongly on PEG-DMPE concentration, gelation is
uncorrelated to changes in membrane elasticity.
PMID- 9649388
TI - Dynamic excitations in membranes induced by optical tweezers.
AB - We present the phenomenology of transformations in lipid bilayers that are
excited by laser tweezers. A variety of dynamic instabilities and shape
transformations are observed, including the pearling instability, expulsion of
vesicles, and more exotic ones, such as the formation of passages. Our physical
picture of the laser-membrane interaction is based on the generation of tension
in the bilayer and loss of surface area. Although tension is the origin of the
pearling instability, it does not suffice to explain expulsion of vesicles, where
we observe opening of giant pores and creeping motion of bilayers. We present a
quantitative theoretical framework to understand most of the observed
phenomenology. The main hypothesis is that lipid is pulled into the optical trap
by the familiar dielectric effect, is disrupted, and finally is repackaged into
an optically unresolvable suspension of colloidal particles. This suspension, in
turn, can produce osmotic pressure and depletion forces, driving the observed
transformations.
PMID- 9649389
TI - Material property characteristics for lipid bilayers containing lysolipid.
AB - The apparent area expansion modulus and tensile strength of egg
phosphatidylcholine (EPC) membranes are measured in the presence of
monooleoylphosphatidylcholine (MOPC). The apparent area expansion modulus
decreases from 171 mN m-1 for pure EPC membrane to 82 mN m-1 for a membrane
containing 30 mol % MOPC. This significant decrease of the apparent area
expansion modulus is attributed to the change of the membrane area due to the
tension-dependent exchange of MOPC between the bathing solution and the membrane.
Similar to the apparent area expansion modulus, the tensile strength of the
membrane decreases with the increase of the molar concentration of MOPC in the
membrane. The tensile strength of pure EPC membrane is 9.4 mN m-1 whereas that
for a membrane containing 30 mol % MOPC is only 1.8 mN m-1, and for a membrane
containing 50 mol % MOPC it is even smaller, on the order of 0.07 mN m-1. The
decrease of the tensile strength is coupled with a decrease of the work for
membrane breakdown, which changes from 4.3 x 10(-2) kT for pure EPC membrane to 2
x 10(-6) kT for a membrane with 50 mol % MOPC. Overall, these results show that
the decrease of the apparent area expansion modulus in the presence of
exchangeable molecules is a fundamental property for all membranes and depends on
the area occupied by these molecules. The method presented here provides a unique
tool for measuring the area occupied by an exchangeable molecule in the bilayer
membrane.
PMID- 9649390
TI - Water dynamics in glycosphingolipid aggregates studied by LAURDAN fluorescence.
AB - We have characterized the fluorescence properties of 6-dodecanoyl-2-dimethylamine
naphthalene (LAURDAN) in pure interfaces formed by sphingomyelin and 10
chemically related glycosphingolipids (GSLs).1 The GSLs contain neutral and
anionic carbohydrate residues in their oligosaccharide chain. These systems were
studied at temperatures below, at, or above the main phase transition temperature
of the pure lipid aggregates. The extent of solvent dipolar relaxation around the
excited fluorescence probe in the GSLs series increases with the magnitude of the
glycosphingolipid polar headgroup below the transition temperature. This
conclusion is based on LAURDAN's excitation generalized polarization (GPex) and
fluorescence lifetime values found in the different interfaces. A linear
dependence between the LAURDAN GPex and the intermolecular spacing among the
lipid molecules was found for both neutral and anionic lipids in the GSLs series.
This relationship was also followed by phospholipids. We conclude that LAURDAN in
these lipid aggregates resides in sites containing different amounts of water.
The dimension of these sites increases with the size of the GSLs polar headgroup.
The GP function reports on the concentration and dynamics of water molecules in
these sites. Upon addition of cholesterol to Gg4Cer, the fluorescence behavior of
LAURDAN was similar to that of pure cerebrosides and sphingomyelin vesicles. This
observation was attributed to a change in the interfacial hydration as well as
changes in the shape and size of the Gg4Cer aggregates in the presence of
cholesterol. After the addition of cholesterol to gangliosides, the changes in
the LAURDAN's spectral parameters decrease progressively as the polar headgroup
of these lipids becomes more complex. This finding suggests that the dehydration
effect of cholesterol depends strongly on the curvature radius and the extent of
hydration of these lipid aggregates. In the gel phase of phrenosine, GalCer,
Gg3Cer, sulfatide, and sphingomyelin, the excitation red band (410 nm) of LAURDAN
was reduced with respect to that of LAURDAN in the gel phase of pure
phospholipids. This observation indicates a local environment that interacts
differently with the ground state of LAURDAN in GSLs when compared with LAURDAN
in phospholipids.
PMID- 9649391
TI - Submicron structure in L-alpha-dipalmitoylphosphatidylcholine monolayers and
bilayers probed with confocal, atomic force, and near-field microscopy.
AB - Langmuir-Blodgett (LB) monolayers and bilayers of L-alpha
dipalmitoylphosphatidylcholine (DPPC), fluorescently doped with 1,1'-dioctadecyl
3,3,3',3'-tetramethylindocarbocyanine perchlorate (diIC18), are studied by
confocal microscopy, atomic force microscopy (AFM), and near-field scanning
optical microscopy (NSOM). Beyond the resolution limit of confocal microscopy,
both AFM and NSOM measurements of mica-supported lipid monolayers reveal small
domains on the submicron scale. In the NSOM studies, simultaneous high-resolution
fluorescence and topography measurements of these structures confirm that they
arise from coexisting liquid condensed (LC) and liquid expanded (LE) lipid
phases, and not defects in the monolayer. AFM studies of bilayers formed by a
combination of LB dipping and Langmuir-Schaefer monolayer transfer exhibit
complex surface topographies that reflect a convolution of the phase structure
present in each of the individual monolayers. NSOM fluorescence measurements,
however, are able to resolve the underlying lipid domains from each side of the
bilayer and show that they are qualitatively similar to those observed in the
monolayers. The observation of the small lipid domains in these bilayers is
beyond the spatial resolving power of confocal microscopy and is complicated in
the topography measurements taken with AFM, illustrating the utility of NSOM for
these types of studies. The data suggest that the small LC and LE lipid domains
are formed after lipid transfer to the substrate through a dewetting mechanism.
The possible extension of these measurements to probing for lipid phase domains
in natural biomembranes is discussed.
PMID- 9649392
TI - Nonaxiality in infrared dichroic ratios of polytopic transmembrane proteins.
AB - In polytopic alpha-helical transmembrane proteins, the distribution of amide
vibrational transition moments can be nonaxial, if the helix axes are tilted
relative to the symmetry axis of the helix bundle. The infrared dichroic ratios
from oriented samples then contain nonaxial terms and, in the most general case,
require a second-order parameter for the axis of the helix bundle. The extent of
nonaxiality depends on the summation over the individual amide transition moments
along the helix. Because this is strongly oscillatory, with a 3.6-residue
periodicity, complete axial symmetry is not achieved rapidly on progressive
summation. Expressions for the contributions of residual nonaxiality to the
dichroic ratios are derived. A similar situation arises for oligomers of
transmembrane beta-barrel proteins, e.g., the porin trimer. In this case, the
extent of nonaxiality depends not only on the number of residues in the beta
barrel, but also on the tilt of the beta-strands relative to the barrel axis and
the characteristic dimensions of a beta-sheet, which together determine the axial
periodicity. The nonaxial contributions to the dichroic ratios of beta-barrel
oligomers are also derived. Estimates are given of the likely size of the
nonaxial contributions for the different alpha-helical and beta-sheet systems.
PMID- 9649393
TI - Na-Ca exchange and the trigger for sarcoplasmic reticulum Ca release: studies in
adult rabbit ventricular myocytes.
AB - The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum (SR) Ca
release remains controversial. Therefore, we measured whole-cell Ca currents
(ICa), Na-Ca exchange currents (INaCa), cellular contractions, and intracellular
Ca transients in adult rabbit cardiac myocytes. We found that changing pipette Na
concentration markedly affected the relationship between cell shortening (or Ca
transients) and voltage, but did not affect the Ca current-voltage relationship.
We then inhibited Na-Ca exchange and varied SR content (by changing the number of
conditioning pulses before each test pulse). Regardless of SR Ca content, the
relationship between contraction and voltage was bell-shaped in the absence of Na
Ca exchange. Next, we rapidly and completely blocked ICa by applying nifedipine
to cells. Cellular shortening was variably reduced in the presence of nifedipine.
The component of shortening blocked by nifedipine had a bell-shaped relationship
with voltage, whereas the "nifedipine-insensitive" component of contraction
increased with voltage. With the SR disabled (ryanodine and thapsigargin
pretreatment), ICa could initiate late-peaking contractions that were
approximately 70% of control amplitude. In contrast, nifedipine-insensitive
contractions could not be elicited in the presence of ryanodine and thapsigargin.
Finally, we recorded reverse Na-Ca exchange currents that were activated by
membrane depolarization. The estimated sarcolemmal Ca flux occurring by Na-Ca
exchange (during voltage clamp steps to +30 mV) was approximately 10-fold less
than that occurring by ICa. Therefore, Na-Ca exchange alone is unlikely to raise
cytosolic Ca concentration enough to directly activate the myofilaments. We
conclude that reverse Na-Ca exchange can trigger SR Ca release. Because of the
sigmoidal relationship between the open probability of the SR Ca release channel
and pCa, the effects of ICa and INaCa may not sum in a linear fashion. Rather,
the two triggers may act synergistically in the modulation of SR release.
PMID- 9649394
TI - Sequence-dependent dynamics of TATA-Box binding sites.
AB - We have carried out two nanosecond-length molecular dynamics simulations on a DNA
oligomer, d(GCGTAAAAAAAACGC)2, which contains a weak binding site for the TATA
box binding protein. An analysis of the resulting trajectories shows that this
oligomer behaves differently from a related oligomer [d(GCGTATATAAAACGC)2]
studied earlier using the same protocol (Flatters, D., M. Young, D. L. Beveridge,
and R. Lavery. 1997. Conformational properties of the TATA-box binding sequence
of DNA. J. Biomol. Struct. & Dyn. 14:757-765), and which contains a strong
binding site for the same protein. The two basepair mutations that relate these
oligomers lead to significant changes in time-averaged structure and in dynamic
behavior, which extend over entire length of the oligomer and appear to be
compatible with the experimentally observed decrease of binding and functional
activity. These results suggest that molecular dynamics simulations, taking into
account explicit solvent and counterions, and avoiding the truncation of
electrostatic interactions, are a powerful tool for investigating the indirect
aspects of protein-nucleic acid recognition.
PMID- 9649395
TI - Contribution of proton release to the B2 photocurrent of bacteriorhodopsin.
AB - The contribution of proton release from the so-called proton release group to the
microsecond B2 photocurrent from bacteriorhodopsin (bR) oriented in
polyacrylamide gels was determined. The fraction of the B2 current due to proton
release was resolved by titration of the proton release group in M. At pH values
below the pKa of the proton release group in M, the proton release group cannot
release its proton during the first half of the bacteriorhodopsin photocycle. At
these pH values, the B2 photocurrent is due primarily to translocation of the
Schiff base proton to Asp85. The B2 photocurrent was measured in wild-type bR
gels at pH 4.5-7.5, in 100 mM KCl/50 mM phosphate. The B2 photocurrent area
(proportional to the amount of charge moved) exhibits a pH dependence with a pKa
of 6.1. This is suggested to be the pKa of the proton release group in M; the
value obtained is in good agreement with previous results obtained by examining
photocycle kinetics and pH-sensitive dye signals. In the mutant Glu204Gln, the B2
photocurrent of the mutant membranes was pH independent between pH 4 and 7.
Because the proton release group is incapacitated, and early proton release is
eliminated in the Glu204Gln mutant, this supports the idea that the pH dependence
of the B2 photocurrent in the wild type reflects the titration of the proton
release group. In wild-type bacteriorhodopsin, proton release contributes
approximately half of the B2 area at pH 7.5. The B2 area in the Glu204Gln mutant
is similar to that in the wild type at pH 4.5; in both cases, the B2 current is
likely due only to movement of the Schiff base proton to Asp85.
PMID- 9649396
TI - Fluorescence and absorption spectroscopy of the weakly fluorescent chlorophyll a
in cytochrome b6f of Synechocystis PCC6803.
AB - A spectroscopic characterization of the chlorophyll a (Chl) molecule in the
monomeric cytochrome b6f complex (Cytb6f) isolated from the cyanobacterium
Synechocystis PCC6803 is presented. The fluorescence lifetime and quantum yield
have been determined, and it is shown that Chl in Cytb6f has an excited-state
lifetime that is 20 times smaller than that of Chl in methanol. This shortening
of the Chl excited state lifetime is not caused by an increased rate of
intersystem crossing. Most probably it is due to quenching by a nearby amino
acid. It is suggested that this quenching is a mechanism for preventing the
formation of Chl triplets, which can lead to the formation of harmful singlet
oxygen. Using site-selected fluorescence spectroscopy, detailed information on
vibrational frequencies in both the ground and Qy excited states has been
obtained. The vibrational frequencies indicate that the Chl molecule has one
axial ligand bound to its central magnesium and accepts a hydrogen bond to its
13(1)-keto carbonyl. The results show that the Chl binds to a well-defined pocket
of the protein and experiences several close contacts with nearby amino acids.
From the site-selected fluorescence spectra, it is further concluded that the
electron-phonon coupling is moderately strong. Simulations of both the site
selected fluorescence spectra and the temperature dependence of absorption and
fluorescence spectra are presented. These simulations indicate that the Huang
Rhys factor characterizing the electron-phonon coupling strength is between 0.6
and 0.9. The width of the Gaussian inhomogeneous distribution function is 210 +/-
10 cm-1.
PMID- 9649397
TI - Evidence for charge-controlled conformational changes in the photocycle of
bacteriorhodopsin.
AB - The existence of two different M-state structures in the photocycle of the
bacteriorhodopsin mutant ASP38ARG was proved. At pH 6.7 (0 to -6 degreesC) a
spectroscopic M intermediate (M1) that does not differ significantly in its
tertiary structure from the light-adapted ground state accumulates under
illumination. At pH > 9 another state (M2), characterized by additional
pronounced changes in the Fourier transform infrared difference spectrum in the
region of the amide I and II bands, accumulates. The M2 intermediate trapped at
pH 9.6 displays the same changes in the x-ray diffraction intensities under
continuous illumination as previously described for x-ray experiments with the
mutant ASP96ASN. These observations indicate that in this mutant the altered
charge distribution at neutral pH controls the tertiary structural changes that
seem to be necessary for proton translocation.
PMID- 9649398
TI - New photocycle intermediates in the photoactive yellow protein from
Ectothiorhodospira halophila: picosecond transient absorption spectroscopy.
AB - Previous studies have shown that the room temperature photocycle of the
photoactive yellow protein (PYP) from Ectothiorhodospira halophila involves at
least two intermediate species: I1, which forms in <10 ns and decays with a 200
micros lifetime to I2, which itself subsequently returns to the ground state with
a 140-ms time constant at pH 7 (Genick et al. 1997. Biochemistry. 36:8-14).
Picosecond transient absorption spectroscopy has been used here to reveal a
photophysical relaxation process (stimulated emission) and photochemical
intermediates in the PYP photocycle that have not been reported previously. The
first new intermediate (I0) exhibits maximum absorption at approximately 510 nm
and appears in =3 ps after 452 nm excitation (5 ps pulse width) of PYP. Kinetic
analysis shows that I0 decays with a 220 +/- 20 ps lifetime, forming another
intermediate (Idouble dagger0) that has a similar difference wavelength maximum,
but with lower absorptivity. Idouble dagger0 decays with a 3 +/- 0.15 ns time
constant to form I1. Stimulated emission from an excited electronic state of PYP
is observed both within the 4-6-ps cross-correlation times used in this work, and
with a 16-ps delay for all probe wavelengths throughout the 426-525-nm region
studied. These transient absorption and emission data provide a more detailed
understanding of the mechanistic dynamics occurring during the PYP photocycle.
PMID- 9649400
TI - International symposium on protein condensation, in honor of gregorio weber, may
21-25, 1997, rio de janeiro, brazil
PMID- 9649399
TI - Effective light-induced hydroxylamine reactions occur with C13 = C14
nonisomerizable bacteriorhodopsin pigments.
AB - The light-driven proton pump bacteriorhodopsin (bR) undergoes a bleaching
reaction with hydroxylamine in the dark, which is markedly catalyzed by light.
The reaction involves cleavage of the (protonated) Schiff base bond, which links
the retinyl chromophore to the protein. The catalytic light effect is currently
attributed to the conformational changes associated with the photocycle of all
trans bR, which is responsible for its proton pump mechanism and is initiated by
the all-trans --> 13-cis isomerization. This hypothesis is now being tested in a
series of experiments, at various temperatures, using three artificial bR
molecules in which the essential C13==C14 bond is locked by a rigid ring
structure into an all-trans or 13-cis configuration. In all three cases we
observe an enhancement of the reaction by light despite the fact that, because of
locking of the C13==C14 bond, these molecules do not exhibit a photocycle, or any
proton-pump activity. An analysis of the rate parameters excludes the possibility
that the light-catalyzed reaction takes place during the approximately 20-ps
excited state lifetimes of the locked pigments. It is concluded that the reaction
is associated with a relatively long-lived (micros-ms) light-induced
conformational change that is not reflected by changes in the optical spectrum of
the retinyl chromophore. It is plausible that analogous changes (coupled to those
of the photocycle) are also operative in the cases of native bR and visual
pigments. These conclusions are discussed in view of the light-induced
conformational changes recently detected in native and artificial bR with an
atomic force sensor.
PMID- 9649401
TI - Gregorio Weber, 1916-1997: a fluorescent lifetime.
PMID- 9649402
TI - A helix propensity scale based on experimental studies of peptides and proteins.
AB - The average globular protein contains 30% alpha-helix, the most common type of
secondary structure. Some amino acids occur more frequently in alpha-helices than
others; this tendency is known as helix propensity. Here we derive a helix
propensity scale for solvent-exposed residues in the middle positions of alpha
helices. The scale is based on measurements of helix propensity in 11 systems,
including both proteins and peptides. Alanine has the highest helix propensity,
and, excluding proline, glycine has the lowest, approximately 1 kcal/mol less
favorable than alanine. Based on our analysis, the helix propensities of the
amino acids are as follows (kcal/mol): Ala = 0, Leu = 0.21, Arg = 0.21, Met =
0.24, Lys = 0.26, Gln = 0.39, Glu = 0.40, Ile = 0.41, Trp = 0.49, Ser = 0.50, Tyr
= 0. 53, Phe = 0.54, Val = 0.61, His = 0.61, Asn = 0.65, Thr = 0.66, Cys = 0.68,
Asp = 0.69, and Gly = 1.
PMID- 9649403
TI - Protein folding: matching theory and experiment.
AB - The impact of folding funnels and folding simulations on the way experimentalists
interpret results is examined. The image of the transition state has changed from
a unique species that has a strained configuration, with a correspondingly high
free energy, to a more ordinary folding intermediate, whose balance between
limited conformational entropy and stabilizing contacts places it at the top of
the free energy barrier. Evidence for a broad transition barrier comes from
studies showing that mutations can change the position of the barrier. The main
controversial issue now is whether populated folding intermediates are productive
on-pathway intermediates or dead-end traps. Direct experimental evidence is
needed. Theories suggesting that populated intermediates are trapped in a
glasslike state are usually based on mechanisms which imply that trapping would
only be extremely short-lived (e.g., nanoseconds) in water at 25 degrees C. There
seems to be little experimental evidence for long-lived trapping in monomers, if
folding aggregates are excluded. On the other hand, there is good evidence for
kinetic trapping in dimers. alpha-Helix formation is currently the fastest known
process in protein folding, and incipient helices are present at the start of
folding. Fast helix formation has the effect of narrowing drastically the choice
of folding routes. Thus helix formation can direct folding. It changes the
folding metaphor from pouring liquid down a folding funnel to a train leaving a
switchyard with only a few choices of exit tracks.
PMID- 9649404
TI - Thermodynamic volume cycles for electron transfer in the cytochrome c oxidase and
for the binding of cytochrome c to cytochrome c oxidase.
AB - Dilatometry is a sensitive technique for measuring volume changes occurring
during a chemical reaction. We applied it to the reduction-oxidation cycle of
cytochrome c oxidase, and to the binding of cytochrome c to the oxidase. We
measured the volume changes that occur during the interconversion of oxidase
intermediates. The numerical values of these volume changes have allowed the
construction of a thermodynamic cycle that includes many of the redox
intermediates. The system volume for each of the intermediates is different. We
suggest that these differences arise by two mechanisms that are not mutually
exclusive: intermediates in the catalytic cycle could be hydrated to different
extents, and/or small voids in the protein could open and close. Based on our
experience with osmotic stress, we believe that at least a portion of the volume
changes represent the obligatory movement of solvent into and out of the oxidase
during the combined electron and proton transfer process. The volume changes
associated with the binding of cytochrome c to cytochrome c oxidase have been
studied as a function of the redox state of the two proteins. The volume changes
determined by dilatometry are large and negative. The data indicate quite clearly
that there are structural alterations in the two proteins that occur on complex
formation.
PMID- 9649405
TI - High-resolution, high-pressure NMR studies of proteins.
AB - Advanced high-resolution NMR spectroscopy, including two-dimensional NMR
techniques, combined with high pressure capability, represents a powerful new
tool in the study of proteins. This contribution is organized in the following
way. First, the specialized instrumentation needed for high-pressure NMR
experiments is discussed, with specific emphasis on the design features and
performance characteristics of a high-sensitivity, high-resolution, variable
temperature NMR probe operating at 500 MHz and at pressures of up to 500 MPa. An
overview of several recent studies using 1D and 2D high-resolution, high-pressure
NMR spectroscopy to investigate the pressure-induced reversible unfolding and
pressure-assisted cold denaturation of lysozyme, ribonuclease A, and ubiquitin is
presented. Specifically, the relationship between the residual secondary
structure of pressure-assisted, cold-denatured states and the structure of early
folding intermediates is discussed.
PMID- 9649406
TI - Reversible stalling of transcription elongation complexes by high pressure.
AB - We have investigated the effect of high hydrostatic pressure on the stability of
RNA polymerase molecules during transcription. RNA polymerase molecules
participating in stalled or active ternary transcribing complexes do not
dissociate from the template DNA and nascent RNA at pressures up to 180 MPa. A
lower limit for the free energy of stabilization of an elongating ternary complex
relative to the quaternary structure of the free RNAP molecules is estimated to
be 20 kcal/mol. The rate of elongation decreases at high pressure; transcription
completely halts at sufficiently high pressure. The overall rate of elongation
has an apparent activation volume (DeltaVdouble dagger) of 55-65 ml . mol-1 (at
35 degrees C). The pressure-stalled transcripts are stable and resume elongation
at the prepressure rate upon decompression. The efficiency of termination
decreases at the rho-independent terminator tR2 after the transcription reaction
has been exposed to high pressure. This suggests that high pressure modifies the
ternary complex such that termination is affected in a manner different from that
of elongation. The solvent and temperature dependence of the pressure-induced
inhibition show evidence for major conformational changes in the core polymerase
enzyme during RNA synthesis. It is proposed that the inhibition of the elongation
phase of the transcription reaction at elevated pressures is related to a
reduction of the partial specific volume of the RNA polymerase molecule; under
high pressure, the RNA polymerase molecule does not have the necessary structural
flexibility required for the protein to translocate.
PMID- 9649407
TI - Determination of the volume changes for pressure-induced transitions of
apomyoglobin between the native, molten globule, and unfolded states.
AB - The volume change for the transition from the native state of horse heart
apomyoglobin to a pressure-induced intermediate with fluorescence properties
similar to those of the well-established molten globule or I form was measured to
be -70 ml/mol. Complete unfolding of the protein by pressure at pH 4.2 revealed
an upper limit for the unfolding of the intermediate of -61 ml/mol. At 0.3 M
guanidine hydrochloride, the entire transition from native to molten globule to
unfolded state was observed in the available pressure range below 2.5 kbar. The
volume change for the N-->I transition is relatively large and does not correlate
well with the changes in relative hydration for these transitions derived from
measurements of the changes in heat capacity, consistent with the previously
observed lack of correlation between the m-value for denaturant-induced
transitions and the measured volume change of unfolding for cooperativity mutants
of staphylococcal nuclease (Frye et al. 1996. Biochemistry. 35:10234-10239). Our
results support the hypothesis that the volume change associated with the
hydration of protein surface upon unfolding may involve both positive and
negative underlying contributions that effectively cancel, and that the measured
volume changes for protein structural transitions arise from another source,
perhaps the elimination of void volume due to packing defects in the structured
chains.
PMID- 9649408
TI - Pressure-induced subunit dissociation and unfolding of dimeric beta
lactoglobulin.
AB - Effects of hydrostatic pressure on dimeric beta-lactoglobulin A (beta-Lg) were
investigated. Application of pressures of up to 3.5 kbar induced a significant
red shift ( approximately 11 nm) and a 60% increase in intrinsic fluorescence
emission of beta-Lg. These changes were very similar to those induced by
guanidine hydrochloride, which caused subunit dissociation and unfolding of beta
Lg. A large hysteresis in the recovery of fluorescence parameters was observed
upon decompression of beta-Lg. Pressure-induced dissociation and unfolding were
not fully reversible, because of the formation of a nonnative intersubunit
disulfide bond that hampered correct refolding of the dimer. Comparison between
pressure dissociation/unfolding at 3 degrees C and 23 degrees C revealed a marked
destabilization of beta-Lg at low temperature. The stability of beta-Lg toward
pressure was significantly enhanced by 1 M NaCl, but not by glycerol (up to 20%
v/v). These observations suggest that salt stabilization was not related to a
general cosolvent effect, but may reflect charge screening. Interestingly,
pressure-induced dissociation/unfolding was completely independent of beta-Lg
concentration, in apparent violation of the law of mass action. Possible causes
for this anomalous behavior are discussed.
PMID- 9649409
TI - Differential halothane binding and effects on serum albumin and myoglobin.
AB - To understand further the weak molecular interactions between inhaled anesthetics
and proteins, we studied the character and dynamic consequences of halothane
binding to bovine serum albumin (BSA) and myoglobin using photoaffinity labeling
and hydrogen-tritium exchange (HX). We find that halothane binds saturably and
with submillimolar affinity to BSA, but either nonspecifically or with
considerably lower affinity to myoglobin. Titration of halothane binding with
guanidine hydrochloride suggested more protection of binding sites from solvent
in BSA as compared with myoglobin. Protection factors for slowly exchanging
albumin hydrogens are increased in a concentration-dependent manner by up to 27
fold with 10 mM halothane, whereas more rapidly exchanging groups of albumin
hydrogens have either unaltered or decreased protection factors. Protection
factors for slowly exchanging hydrogens in myoglobin are decreased by halothane,
suggesting destabilization through binding to an intermediate or completely
unfolded conformer. These results demonstrate the conformation dependence of
halothane binding and clear dynamic consequences that correlate with the
character of binding in these model proteins. Preferential binding and
stabilization of different conformational states may underlie anesthetic-induced
protein dysfunction, as well as provide an explanation for heterogeneity of
action.
PMID- 9649410
TI - Chemical denaturation: potential impact of undetected intermediates in the free
energy of unfolding and m-values obtained from a two-state assumption.
AB - The chemical unfolding transition of a protein was simulated, including the
presence of an intermediate (I) in equilibrium with the native (N) and unfolded
(U) states. The calculations included free energies of unfolding, DeltaGuw, in
the range of 1.4 kcal/mol to 10 kcal/mol and three different global m-values. The
simulations included a broad range of equilibrium constants for the N left arrow
over right arrow I process. The dependence of the N <--> I equilibrium on the
concentration of denaturant was also included in the simulations. Apparent
DeltaGuw and m-values were obtained from the simulated unfolding transitions by
fitting the data to a two-state unfolding process. The potential errors were
calculated for two typical experimental situations: 1) the unfolding is monitored
by a physical property that does not distinguish between native and intermediate
states (case I), and 2) the physical property does not distinguish between
intermediate and unfolded states (case II). The results obtained indicated that
in the presence of an intermediate, and in both experimental situations, the free
energy of unfolding and the m-values could be largely underestimated. The errors
in DeltaGuw and m-values do not depend on the m-values that characterize the
global N <--> U transition. They are dependent on the equilibrium constant for
the N <--> I transition and its characteristic m1-value. The extent of the
underestimation increases for higher energies of unfolding. Including no random
error in the simulations, it was estimated that the underestimation in DeltaGuw
could range between 25% and 35% for unfolding transitions of 3-10 kcal/mol (case
I). In case II, the underestimation in DeltaGuw could be even larger than in case
I. In the same energy range, a 50% error in the m-value could also take place.
The fact that most of the mutant proteins are characterized by both a lower m
value and a lower stability than the wild-type protein suggests that in some
cases the results could have been underestimated due to the application of the
two-state assumption.
PMID- 9649411
TI - Partition and permeation of dextran in polyacrylamide gel.
AB - Partition of sized FITC-dextrans in polyacrylamide gel showed a relationship
between Kav and solute radius as predicted by the theory of Ogston, which is
based solely on geometry of the spaces. Permeability data for the same dextrans
were fit to several theories, including those based on geometry and those based
on hydrodynamic interactions, and the gel structure predicted by the partition
and permeability data were compared. The Brinkman effective-medium model (based
on hydrodynamic interactions and requiring a measure of the hydraulic
conductivity of the matrix) gave the best fit of permeability data with the
values for fiber radius (rf) and void volume of the gel (epsilon) that were
obtained from the partition data. The models based on geometry and the
hydrodynamic screening model of Cukier, using the rf and epsilon from partition
data, all predicted higher rates of permeation than observed experimentally,
while the effective-medium model with added term for steric interaction predicted
lower permeation than that observed. The size of cylindrical pores appropriate
for the partition data predicted higher rates of permeation than observed. These
relative results were unaffected by the method of estimating void volume of the
gel. In sum, it appears that one can use data on partition of solute, combined
with measurement of hydraulic conductivity, to predict solute permeation in
polyacrylamide gel.
PMID- 9649412
TI - Model for the fluorescence induction curve of photoinhibited thylakoids.
AB - The fluorescence induction curve of photoinhibited thylakoids measured in the
presence of 3-(3,4-dichlorophenyl)-1,1-dimethyl urea was modeled using an
extension of the model of Lavergne and Trissl (Biophys. J. 68:2474-2492), which
takes into account the reversible exciton trapping by photosystem II (PSII)
reaction centers and exciton exchange between PSII units. The model of Trissl and
Lavergne was modified by assuming that PSII consists of photosynthetically active
and photoinhibited (inactive in oxygen evolution) units and that the inactive
PSII units can efficiently dissipate energy even if they still retain the
capacity for the charge separation reaction. Comparison of theoretical and
experimental fluorescence induction curves of thylakoids, which had been
subjected to strong light in the presence of the uncoupler nigericin, suggests
connectivity between the photoinhibited and active PSII units. The model predicts
that photoinhibition lowers the yield of radical pair formation in the remaining
active PSII centers. However, the kinetics of PSII inactivation in nigericin
treated thylakoids upon exposure to photoinhibitory light ranging from 185 to
2650 micromol photons m-2 s-1 was strictly exponential. This may suggest that
photoinhibition occurs independently of the primary electron transfer reactions
of PSII or that increased production of harmful substances by photoinhibited PSII
units compensates for the protection afforded by the quenching of excitation
energy in photoinhibited centers.
PMID- 9649413
TI - Scanning force microscopy of DNA molecules elongated by convective fluid flow in
an evaporating droplet.
AB - Scanning force microscopy (SFM) was used to image intact, nearly fully elongated
lambda bacteriophage DNA molecules, fixed onto freshly cleaved mica surfaces.
Molecular elongation and fixation were accomplished using a newly characterized
fixation technique, termed "fluid fixation." Here convective fluid flows
generated within an evaporating droplet of DNA solution efficiently elongate DNA
molecules for fixation onto suitably charged surfaces. SFM images of a very large
bacteriophage genome, G, showed the presence of double-stranded bubbles. We
speculate that these structures may contain putative replication forks. Overall,
the experiments presented here demonstrate the viability of using fluid fixation
for the preparation of DNA molecules for SFM imaging. The combination of largely
automatable optically based techniques with the high-resolution SFM imaging
presented here will likely produce a high-throughput system for detailed physical
mapping of genomic DNA or clones.
PMID- 9649414
TI - Real-time observation of conformational fluctuations in Zn-substituted myoglobin
by time-resolved transient hole-burning spectroscopy.
AB - Equilibrium fluctuations of the protein conformation have been studied in
myoglobin by a novel method of time-resolved transient hole-burning spectroscopy
over a temperature range of 180-300 K and a time range of 10 ns to 10 ms. The
temporal shift of the hole spectrum has been observed in a wide temperature
region of 200-300 K. It has been found that the time behavior of the peak
position of the hole is highly nonexponential and can be expressed by a stretched
exponential function with a beta value of 0.22. As compared with the results for
a dye solution sample, the time scale of the fluctuation of the protein
conformation is much more weakly dependent on temperature. The time scale of the
observed conformational dynamics shows a temperature dependence similar to that
associated with the ligand escape process of myoglobin.
PMID- 9649415
TI - Time-resolved analysis of macromolecular structures during reactions by stopped
flow electrooptics.
AB - A stopped-flow field-jump instrument and its use for the analysis of
macromolecular structure changes during reactions is described. The operation of
the new instrument is simple and reliable, owing to a new type of cell
construction with electrodes directly integrated in a quartz cuvette: major
advantages are the relatively low demand on sample quantities and a high time
resolution. The stopped flow is characterized by a dead time of approximately 0.5
ms. Electric field pulses with field strengths up to 20 kV/cm and rise times in
the nanosecond range are applied at adjustable times after stop of the flow. The
time resolution of the optical detection is up to the nanosecond time range. The
instrument may be used for the combination of stopped flow with temperature-jump
and field-jump experiments. A particularly useful new application is the analysis
of macromolecular reactions by electrooptical measurements, because
electrooptical data provide information about structures. This is demonstrated
for the intercalation of ethidium into double-helical DNA. The transients,
measured at 313 nm, where the signal is exclusively due to ethidium bound to the
DNA, demonstrate a relatively high negative dichroism at 0.5 ms after mixing. The
absolute value of this negative dichroism increases in the millisecond time range
and approaches the equilibrium value within about a second. The dichroism decay
time constants demonstrate a clear increase of the effective DNA length due to
ethidium binding, already 0.5 ms after mixing; a further increase to the
equilibrium value is found in the millisecond time range. The analysis of these
data demonstrate the existence of up to three relaxation processes, depending on
the conditions of the experiments. The dichroism amplitudes, together with the
decay time constants, indicate that all the reaction states found in the present
investigation are complexes with insertion of ethidium residues between
basepairs. Moreover, the data clearly show the degree of intercalation in the
intermediate states, which is very useful information for the quantitative
assignment of the mechanism.
PMID- 9649416
TI - ATP-Induced phosphorylation of the sarcoplasmic reticulum Ca2+ ATPase: molecular
interpretation of infrared difference spectra.
AB - Time-resolved infrared difference spectra of the ATP-induced phosphorylation of
the sarcoplasmic reticulum Ca2+-ATPase have been recorded in H2O and 2H2O at pH
7.0 and 1 degrees C. The reaction was induced by ATP release from P3-1-(2
nitro)phenylethyladenosine 5'-triphosphate (caged ATP) and from [gamma-18O3]caged
ATP. A band at 1546 cm-1, not observed with the deuterated enzyme, can be
assigned to the amide II mode of the protein backbone and indicates that a
conformational change associated with ATPase phosphorylation takes place after
ATP binding. This is also indicated between 1700 and 1610 cm-1, where bandshifts
of up to 10 cm-1 observed upon protein deuteration suggest that amide I modes of
the protein backbone dominate the difference spectrum. From the band positions it
is deduced that alpha-helical, beta-sheet, and probably beta-turn structures are
affected in the phosphorylation reaction. Model spectra of acetyl phosphate,
acetate, ATP, and ADP suggest the tentative assignment of some of the bands of
the phosphorylation spectrum to the molecular groups of ATP and Asp351, which
participate directly in the phosphate transfer reaction: a positive band at 1719
cm-1 to the C==O group of aspartyl phosphate, a negative band at 1239 cm-1 to the
nuas(PO2-) modes of the bound ATP molecule, and a positive band at 1131 cm-1 to
the nuas(PO32-) mode of the phosphoenzyme phosphate group, the latter assignment
being supported by the band's sensitivity toward isotopic substitution in the
gamma-phosphate of ATP. Band positions and shapes of these bands indicate that
the alpha- and/or beta-phosphate(s) of the bound ATP molecule become partly
dehydrated when ATP binds to the ATPase, that the phosphoenzyme phosphate group
is unprotonated at pH 7.0, and that the C==O group of aspartyl phosphate does not
interact with bulk water. The Ca2+ binding sites seem to be largely undisturbed
by the phosphorylation reaction, and a functional role of the side chains of Asn,
Gln, and Arg residues was not detected.
PMID- 9649417
TI - Energy of adhesion of human T cells to adsorption layers of monoclonal antibodies
measured by a film trapping technique.
AB - A novel method for studying the interaction of biological cells with interfaces
(e.g., adsorption monolayers of antibodies) is developed. The method is called
the film trapping technique because the cell is trapped within an aqueous film of
equilibrium thickness smaller than the cell diameter. A liquid film of uneven
thickness is formed around the trapped cell. When observed in reflected
monochromatic light, this film exhibits an interference pattern of concentric
bright and dark fringes. From the radii of the fringes one can restore the shape
of interfaces and the cell. Furthermore, one can calculate the adhesive energy
between the cell membrane and the aqueous film surface (which is covered by a
layer of adsorbed proteins and/or specific ligands), as well as the disjoining
pressure, representing the force of interaction per unit area of the latter film.
The method is applied to two human T cell lines: Jurkat and its T cell receptor
negative (TCR-) derivative. The interaction of these cells with monolayers of
three different monoclonal antibodies adsorbed at a water-air interface is
studied. The results show that the adhesive energy is considerable (above 0.5
mJ/m2) when the adsorption monolayer contains antibodies acting as specific
ligands for the receptors expressed on the cell surface. In contrast, the
adhesive energy is close to zero in the absence of such a specific ligand
receptor interaction. In principle, the method can be applied to the study of the
interaction of a variety of biological cells (B cells, natural killer cells, red
blood cells, etc.) with adsorption monolayers of various biologically active
molecules. In particular, film trapping provides a tool for the gentle
micromanipulation of cells and for monitoring of processes (say the activation of
a T lymphocyte) occurring at the single-cell level.
PMID- 9649418
TI - Analysis of fluorophore diffusion by continuous distributions of diffusion
coefficients: application to photobleaching measurements of multicomponent and
anomalous diffusion.
AB - Fluorescence recovery after photobleaching (FRAP) is widely used to measure
fluorophore diffusion in artificial solutions and cellular compartments. Two new
strategies to analyze FRAP data were investigated theoretically and applied to
complex systems with anomalous diffusion or multiple diffusing species: 1)
continuous distributions of diffusion coefficients, alpha(D), and 2) time
dependent diffusion coefficients, D(t). A regression procedure utilizing the
maximum entropy method was developed to resolve alpha(D) from fluorescence
recovery curves, F(t). The recovery of multi-component alpha(D) from simulated
F(t) with random noise was demonstrated and limitations of the method were
defined. Single narrow Gaussian alpha(D) were recovered for FRAP measurements of
thin films of fluorescein and size-fractionated FITC-dextrans and Ficolls, and
multi-component alpha(D) were recovered for defined fluorophore mixtures. Single
Gaussian alpha(D) were also recovered for solute diffusion in viscous media
containing high dextran concentrations. To identify anomalous diffusion from FRAP
data, a theory was developed to compute F(t) and alpha(D) for anomalous diffusion
models defined by arbitrary nonlinear mean-squared displacement versus time
relations. Several characteristic alpha(D) profiles for anomalous diffusion were
found, including broad alpha(D) for subdiffusion, and alpha(D) with negative
amplitudes for superdiffusion. A method to deduce apparent D(t) from F(t) was
also developed and shown to provide useful complementary information to alpha(D).
alpha(D) and D(t) were determined from photobleaching measurements of systems
with apparent anomalous subdiffusion (nonuniform solution layer) and
superdiffusion (moving fluid layer). The results establish a practical strategy
to characterize complex diffusive phenomena from photobleaching recovery
measurements.
PMID- 9649419
TI - A possible molecular mechanism governing human erythrocyte shape.
PMID- 9649420
TI - Does the transmembrane potential (Deltapsi) or the intracellular pH (pHi) control
the shape of human erythrocytes?
PMID- 9649421
TI - Transducing Hedgehog: the story so far.
AB - The secreted proteins of the Hedgehog family have been implicated in many
different processes in vertebrate development including cartilage
differentiation, myotome and sclerotome specification, hair follicle development,
limb morphogenesis and the specification of different neuronal cell types. In
addition, the aberrant activation of the Hedgehog pathway has been identified as
the likely cause of a number of tumours in humans including basal cell carcinomas
(BCCs) and primitive neurectodermal tumours (PNETs). Elucidating the mechanisms
by which Hedgehog signals are transduced will thus have widespread implications
for our understanding of both normal development and disease.
PMID- 9649422
TI - Potent enzyme inhibitors derived from dromedary heavy-chain antibodies.
AB - Evidence is provided that dromedary heavy-chain antibodies, in vivo-matured in
the absence of light chains, are a unique source of inhibitory antibodies. After
immunization of a dromedary with bovine erythrocyte carbonic anhydrase and
porcine pancreatic alpha-amylase, it was demonstrated that a considerable amount
of heavy-chain antibodies, acting as true competitive inhibitors, circulate in
the bloodstream. In contrast, the conventional antibodies apparently do not
interact with the enzyme's active site. Next we illustrated that peripheral blood
lymphocytes are suitable for one-step cloning of the variable domain fragments in
a phage-display vector. By bio-panning, several antigen-specific single-domain
fragments are readily isolated for both enzymes. In addition we show that among
those isolated fragments active site binders are well represented. When produced
as recombinant protein in Escherichia coli, these active site binders appear to
be potent enzyme inhibitors when tested in chromogenic assays. The low complexity
of the antigen-binding site of these single-domain antibodies composed of only
three loops could be valuable for designing smaller synthetic inhibitors.
PMID- 9649423
TI - Towards a solution for hepatitis C virus hypervariability: mimotopes of the
hypervariable region 1 can induce antibodies cross-reacting with a large number
of viral variants.
AB - The hypervariable region 1 (HVR1) of the putative envelope protein E2 of
hepatitis C virus (HCV) is the most variable antigenic fragment in the whole
viral genome and is mainly responsible for the large inter-and intra-individual
heterogeneity of the infecting virus. It contains a principal neutralization
epitope and has been proposed as the major player in the mechanism of escape from
host immune response. Since anti-HVR1 antibodies are the only species shown to
possess protective activity up to date, developing an effective prevention
therapy is a very difficult task. We have approached the problem of HVR1
variability by deriving a consensus profile from >200 HVR1 sequences from
different viral isolates and used it as a template to generate a vast repertoire
of synthetic HVR1 surrogates displayed on M13 bacteriophage. This library was
affinity selected using many different sera from infected patients. Phages were
identified which react very frequently with patients' sera and bind serum
antibodies that cross-react with a large panel of HVR1 peptides derived from
natural HCV variants. When injected into experimental animals, the 'mimotopes'
with the highest cross-reactivity induced antibodies which recognized the same
panel of natural HVR1 variants. In these mimotopes we identified a sequence
pattern responsible for the observed cross-reactivity. These data may hold the
key for future development of a prophylactic vaccine against HCV.
PMID- 9649424
TI - Direct link between cytokine activity and a catalytic site for macrophage
migration inhibitory factor.
AB - Macrophage migration inhibitory factor (MIF) is a secreted protein that activates
macrophages, neutrophils and T cells, and is implicated in sepsis, adult
respiratory distress syndrome and rheumatoid arthritis. The mechanism of MIF
function, however, is unknown. The three-dimensional structure of MIF is unlike
that of any other cytokine, but bears striking resemblance to three microbial
enzymes, two of which possess an N-terminal proline that serves as a catalytic
base. Human MIF also possesses an N-terminal proline (Pro-1) that is invariant
among all known homologues. Multiple sequence alignment of these MIF homologues
reveals additional invariant residues that span the entire polypeptide but are in
close proximity to the N-terminal proline in the folded protein. We find that p
hydroxyphenylpyruvate, a catalytic substrate of MIF, binds to the N-terminal
region and interacts with Pro-1. Mutation of Pro-1 to a glycine substantially
reduces the catalytic and cytokine activity of MIF. We suggest that the
underlying biological activity of MIF may be based on an enzymatic reaction. The
identification of the active site should facilitate the development of structure
based inhibitors.
PMID- 9649425
TI - Elongation and clustering of glycosomes in Trypanosoma brucei overexpressing the
glycosomal Pex11p.
AB - Kinetoplastid protozoa confine large parts of glycolysis within glycosomes, which
are microbodies related to peroxisomes. We cloned the gene encoding the second
most abundant integral membrane protein of Trypanosoma brucei glycosomes. The 24
kDa protein is very basic and hydrophobic, with two predicted transmembrane
domains. It is targeted to peroxisomes when expressed in mammalian cells and
yeast. The protein is a functional homologue of Pex11p from Saccharomyces
cerevisiae: pex11Delta mutants, which are defective in peroxisome proliferation,
can be complemented by the trypanosome gene. Sequence conservation is significant
in the N- and C-terminal domains of all putative Pex11p homologues known, from
trypanosomes, yeasts and mammals. Several lines of evidence indicate that these
domains are oriented towards the cytosol. TbPex11p can form homodimers, like its
yeast counterpart. The TbPEX11 gene is essential in trypanosomes. Inducible
overexpression of the protein in T.brucei bloodstream forms causes growth arrest,
the globular glycosomes being transformed to clusters of long tubules filling
significant proportions of the cytoplasm. Reduced expression results in
trypanosomes with fewer, but larger, organelles.
PMID- 9649426
TI - Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth,
stress response and glycogen accumulation.
AB - Yeast cAMP-dependent protein kinase (PKA) activity is essential for growth and
antagonizes induction of the general stress response as well as accumulation of
glycogen stores. Previous studies have suggested that the PKA effects on the two
latter processes result in part from transcription repression. Here we show that
transcription derepression that accompanies PKA depletion is dependent upon the
presence of two redundant Zn2+-finger transcription factors, Msn2p and Msn4p. The
Msn2p and Msn4p proteins were shown previously to act as positive transcriptional
factors in the stress response pathway, and our results suggest that Msn2p and
Msn4p also mediate PKA-dependent effects on stress response as well as glycogen
accumulation genes. Interestingly, PKA activity is dispensable in a strain
lacking Msn2p and Msn4p activity. Thus, Msn2p and Msn4p may antagonize
PKAdependent growth by stimulating expression of genes that inhibit growth. In
agreement with this model, Msn2p/Msn4p function is required for expression of a
gene, YAK1, previously shown to antagonize PKA-dependent growth. These results
suggest that Msn2p/Msn4p-dependent gene expression may account for all, or at
least most, of the pleiotropic effects of yeast PKA, including growth regulation,
response to stress and carbohydrate store accumulation.
PMID- 9649427
TI - Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.
AB - The Xenopus homologue of Drosophila Fizzy and budding yeast CDC20 has been
characterized. The encoded protein (X-FZY) is a component of a high molecular
weight complex distinct from the APC/cyclosome. Antibodies directed against FZY
were produced and shown to prevent calmodulin-dependent protein kinase II
(CaMKII) from inducing the metaphase to anaphase transition of spindles assembled
in vitro in Xenopus egg extracts, and this was associated with suppression of the
degradation of mitotic cyclins. The same antibodies suppressed M phase-promoting
factor (MPF)-dependent activation of the APC/cyclosome in interphase egg
extracts, although they did not appear to alter the pattern or extent of MPF
dependent phosphorylation of APC/cyclosome subunits. As these phosphorylations
are thought to be essential for APC/cyclosome activation in eggs and early
embryos, we conclude that at least two events are required for MPF to activate
the APC/cyclosome, allowing both chromatid segregation and full degradation of
mitotic cyclins. The first one, which does not require FZY function, is the
phosphorylation of APC/cyclosome subunits. The second one, that requires FZY
function (even in the absence of MAD2 protein and when the spindle assembly
checkpoint is not activated) is not yet understood at its molecular level.
PMID- 9649428
TI - Bax-mediated cell death by the Gax homeoprotein requires mitogen activation but
is independent of cell cycle activity.
AB - Tissues with the highest rates of proliferation typically exhibit the highest
frequencies of apoptosis, but the mechanisms that coordinate these processes are
largely unknown. The homeodomain protein Gax is down-regulated when quiescent
cells are stimulated to proliferate, and constitutive Gax expression inhibits
cell proliferation in a p21(WAF/CIP)-dependent manner. To understand how mitogen
induced proliferation influences the apoptotic process, we investigated the
effects of deregulated Gax expression on cell viability. Forced Gax expression
induced apoptosis in mitogen-activated cultures, but quiescent cultures were
resistant to cell death. Though mitogen activation was required for apoptosis,
neither the cdk inhibitor p21(WAF/CIP) nor the tumor suppressor p53 was required
for Gax-induced cell death. Arrest in G1 or S phases of the cell cycle with
chemical inhibitors also did not affect apoptosis, further suggesting that Gax
mediated cell death is independent of cell cycle activity. Forced Gax expression
led to Bcl-2 down-regulation and Bax up-regulation in mitogen-activated, but not
quiescent cultures. Mouse embryonic fibroblasts homozygous null for the Bax gene
were refractive to Gax-induced apoptosis, demonstrating the functional
significance of this regulation. These data suggest that the homeostatic balance
between cell growth and death can be controlled by mitogen-dependent pathways
that circumvent the cell cycle to alter Bcl-2 family protein expression.
PMID- 9649429
TI - p53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity
of p53.
AB - In the interleukin-3 (IL-3)-dependent lymphoid cell line DA-1, functional p53 is
required for efficient apoptosis in response to IL-3 withdrawal. Activation of
p53 in these cells, by either DNA damage or p53 overexpression, results in a
vital growth arrest in the presence of IL-3 and in accelerated apoptosis in its
absence. Thus, IL-3 can control the choice between p53-dependent cell-cycle
arrest and apoptosis. Here we report that the cross-talk between p53 and IL-3
involves joint control of pRb cleavage and degradation. Depletion of IL-3 results
in caspase-mediated pRb cleavage, occurring preferentially within cells which
express functional p53. Moreover, pRb can be cleaved efficiently by extracts
prepared from DA-1 cells but not from their derivatives which lack p53 function.
Inactivation of pRb through expression of the human papillomavirus (HPV) E7
oncogene overrides the effect of IL-3 in a p53-dependent manner. Our data suggest
a novel role for p53 in the regulation of cell death and a novel mechanism for
the cooperation between p53 and survival factor deprivation. Thus, p53 makes
cells permissive to pRb cleavage, probably by controlling the potential activity
of a pRb-cleaving caspase, whereas IL-3 withdrawal provides signals that turn on
this potential activity and lead to the actual cleavage and subsequent
degradation of pRb. Elimination of a presumptive anti-apoptotic effect of pRb may
then facilitate conversion of p53-mediated growth arrest into apoptosis.
PMID- 9649430
TI - Aut2p and Aut7p, two novel microtubule-associated proteins are essential for
delivery of autophagic vesicles to the vacuole.
AB - AUT2 and AUT7, two novel genes essential for autophagocytosis in the yeast
Saccharomyces cerevisiae were isolated. AUT7 was identified as a low copy
suppressor of autophagic defects in aut2-1 cells. Aut7p is a homologue of the rat
microtubule-associated protein (MAP) light chain 3 (LC3). Aut2p and Aut7p
interact physically. Aut7p is attached to microtubules via Aut2p, which interacts
with tubulins Tub1p and Tub2p. aut2- and aut7-deleted cells are unable to deliver
autophagic vesicles and the precursor of aminopeptidase I to the vacuole. Double
membrane-layered autophagosome-like vesicles accumulate in the cytoplasm of these
cells. Our findings suggest that microtubules and an attached protein complex of
Aut2p and Aut7p are involved in the delivery of autophagic vesicles to the
vacuole.
PMID- 9649431
TI - The ubiquitin-conjugating enzyme Pex4p of Hansenula polymorpha is required for
efficient functioning of the PTS1 import machinery.
AB - We have cloned the Hansenula polymorpha PEX4 gene by functional complementation
of a peroxisome-deficient mutant. The PEX4 translation product, Pex4p, is a
member of the ubiquitin-conjugating enzyme family. In H.polymorpha, Pex4p is a
constitutive, low abundance protein. Both the original mutant and the pex4
deletion strain (Deltapex4) showed a specific defect in import of peroxisomal
matrix proteins containing a C-terminal targeting signal (PTS1) and of malate
synthase, whose targeting signal is not yet known. Import of the PTS2 protein
amine oxidase and the insertion of the peroxisomal membrane proteins Pex3p and
Pex14p was not disturbed in Deltapex4 cells. The PTS1 protein import defect in
Deltapex4 cells could be suppressed by overproduction of the PTS1 receptor,
Pex5p, in a dose-response related manner. In such cells, Pex5p is localized in
the cytosol and in peroxisomes. The peroxisome-bound Pex5p specifically
accumulated at the inner surface of the peroxisomal membrane and thus differed
from Pex5p in wild-type peroxisomes, which is localized throughout the matrix. We
hypothesize that in H. polymorpha Pex4p plays an essential role for normal
functioning of Pex5p, possibly in mediating recycling of Pex5p from the
peroxisome to the cytosol.
PMID- 9649432
TI - Identification of novel stress-induced genes downstream of chop.
AB - CHOP (GADD153) is a small nuclear protein that dimerizes avidly with members of
the C/EBP family of transcription factors. Normally undetectable, it is expressed
at high levels in cells exposed to conditions that perturb protein folding in the
endoplasmic reticulum and induce an endoplasmic reticulum stress response. CHOP
expression in stressed cells is linked to the development of programmed cell
death and, in some instances, cellular regeneration. In this study,
representational difference analysis was used to compare the complement of genes
expressed in stressed wild-type mouse embryonic fibroblasts with those expressed
in cells nullizygous for chop. CHOP expression, in concert with a second signal,
was found to be absolutely required for the activation by stress of a set of
previously undescribed genes referred to as DOCs (for downstream of CHOP). DOC4
is a mammalian ortholog of a Drosophila gene, Tenm/Odz, implicated in patterning
of the early fly embryo, whereas DOC6 encodes a newly recognized homolog of the
actin-binding proteins villin and gelsolin. These results reveal the existence of
a novel CHOP-dependent signaling pathway, distinct from the known endoplasmic
reticulum unfolded protein response, which may mediate changes in cell phenotype
in response to stress.
PMID- 9649433
TI - PrlA4 prevents the rejection of signal sequence defective preproteins by
stabilizing the SecA-SecY interaction during the initiation of translocation.
AB - In Escherichia coli, precursor proteins are translocated across the cytoplasmic
membrane by translocase. This multisubunit enzyme consists of a preprotein
binding and ATPase domain, SecA, and the SecYEG complex as the integral membrane
domain. PrlA4 is a mutant of SecY that enables the translocation of preproteins
with a defective, or missing, signal sequence. Inner membranes of the prlA4
strain efficiently translocate Delta8proOmpA, a proOmpA derivative with a non
functional signal sequence. Owing to the signal sequence mutation, Delta8proOmpA
binds to the translocase with a lowered affinity and the recognition is not
restored by the prlA4 SecY. At the ATP-dependent initiation of translocation, the
binding affinity of SecA for SecYEG is lowered causing the premature loss of
bound preproteins from the translocase. The prlA4 membranes, however, bind SecA
with a much higher affinity than the wild-type, and during initiation, the SecA
and preprotein remain bound at the translocation site allowing an improved
efficiency of translocation. It is concluded that the prlA4 strain prevents the
rejection of defective preproteins from the export pathway by stabilizing SecA at
the SecYEG complex.
PMID- 9649434
TI - Overlapping functions of components of a bacterial Sec-independent protein export
pathway.
AB - We describe the identification of two Escherichia coli genes required for the
export of cofactor-containing periplasmic proteins, synthesized with signal
peptides containing a twin arginine motif. Both gene products are homologous to
the maize HCF106 protein required for the translocation of a subset of lumenal
proteins across the thylakoid membrane. Disruption of either gene affects the
export of a range of such proteins, and a complete block is observed when both
genes are inactivated. The Sec protein export pathway was unaffected, indicating
the involvement of the gene products in a novel export system. The accumulation
of active cofactor-containing proteins in the cytoplasm of the mutant strains
suggests a role for the gene products in the translocation of folded proteins.
One of the two HCF106 homologues is encoded by the first gene of a four cistron
operon, tatABCD, and the second by an unlinked gene, tatE. A mutation previously
assigned to the hcf106 homologue encoded at the tatABCD locus, mttA, lies instead
in the tatB gene.
PMID- 9649435
TI - A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+
and the beta-phosphate to destabilize GDP on ARF1.
AB - The Sec7 domain of the guanine nucleotide exchange factor ARNO (ARNO-Sec7) is
responsible for the exchange activity on the small GTP-binding protein ARF1. ARNO
Sec7 forms a stable complex with the nucleotide-free form of [Delta17]ARF1, a
soluble truncated form of ARF1. The crystal structure of ARNO-Sec7 has been
solved recently, and a site-directed mutagenesis approach identified a
hydrophobic groove and an adjacent hydrophilic loop as the ARF1-binding site. We
show that Glu156 in the hydrophilic loop of ARNO-Sec7 is involved in the
destabilization of Mg2+ and GDP from ARF1. The conservative mutation E156D and
the charge reversal mutation E156K reduce the exchange activity of ARNO-Sec7 by
several orders of magnitude. Moreover, [E156K]ARNO-Sec7 forms a complex with the
Mg2+-free form of [Delta17]ARF1-GDP without inducing the release of GDP. Other
mutations in ARNO-Sec7 and in [Delta17]ARF1 suggest that prominent hydrophobic
residues of the switch I region of ARF1 insert into the groove of the Sec7
domain, and that Lys73 of the switch II region of ARF1 forms an ion pair with
Asp183 of ARNO-Sec7.
PMID- 9649436
TI - Stat1 combines signals derived from IFN-gamma and LPS receptors during macrophage
activation.
AB - Complete activation of macrophages during immune responses results from
stimulation with the activating cytokine interferon-gamma (IFN-gamma) and a
second stimulus, usually a microbial product. Bacterial infection of macrophages,
or treatment with bacterial lipopolysaccharide (LPS), resulted in rapid Stat1
phosphorylation on Ser727 (S727) independently of concomitant tyrosine
phosphorylation. IFN-gamma also caused rapid phosphorylation of S727. In both
situations, S727 phosphorylation was reduced by pre-treatment of cells with the
serine kinase inhibitor H7. When macrophages were treated sequentially or
simultaneously with LPS and IFN-gamma, the pool of molecules phosphorylated on
both Tyr701 (Y701) and S727 was strongly increased. Consistently, Stat1-dependent
transcription in response to IFN-gamma was significantly enhanced if the cells
were pre-treated with bacterial LPS. The relative amount of S727-phosphorylated
Stat1 in the non-tyrosine phosphorylated fraction was considerably smaller than
that in the tyrosine-phosphorylated fraction. No evidence was found for an effect
of S727 phosphorylation on the phosphorylation of Y701 by IFN-gamma. Thus, serine
and tyrosine phosphorylation of Stat1 are caused independently of each other, but
the serine kinase may recognize tyrosine-phosphorylated Stat1 preferentially in
the course of an IFN-gamma response. The data suggest Stat1 to be a convergence
point for immunological stimuli in a macrophage proinflammatory response.
PMID- 9649437
TI - Regulation of eosinophil-specific gene expression by a C/EBP-Ets complex and GATA
1.
AB - The EOS47 antigen is an early and specific marker of eosinophil differentiation
in the chicken haematopoietic system. To elucidate the transciptional events
controlling commitment to the eosinophil lineage, we studied the regulation of
the eosinophil-specific EOS47 promoter. This promoter is TATA-less, and binds
trancription factors of the Ets, C/EBP, GATA and Myb families. These sites are
contained within a 309 bp promoter fragment which is sufficient for specific high
level transcription in an eosinophil cell line. Co-transfection experiments in
Q2bn fibroblasts showed cooperative activation of the EOS47 proximal promoter by
c-Myb, Ets-1/Fli-1, GATA-1 and C/EBPalpha. The Ets-1/Fli-1 and C/EBPalpha
proteins were the most potent activators, and acted with high synergy through
juxtaposed binding sites located approximately 60 bp upstream of the
transcription start site. The Ets-1 and C/EBPalpha proteins were found to
associate physically via their DNA-binding domains and to bind their combined
binding site cooperatively. GATA-1 showed biphasic regulation of the EOS47
promoter, activating at low and repressing at high protein concentrations. These
results demonstrate combinatorial activation of an eosinophil-specific promoter
by ubiquitous and lineage-restricted haematopoietic transcription factors. They
also indicate that direct interactions between C/EBPs and specific Ets family
members, together with GATA-1, are important for eosinophil lineage
determination.
PMID- 9649438
TI - Transcription elongation factor P-TEFb mediates Tat activation of HIV-1
transcription at multiple stages.
AB - Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcription
elongation through recognition of the transactivation response (TAR) RNA stem
loop structure at the 5' end of nascent viral transcripts. Recently, a human
transcription elongation factor P-TEFb, consisting of CDK9 kinase, cyclin T and
other associated factors, has been shown to interact with Tat to restore Tat
activation in HeLa nuclear extract depleted of P-TEFb. Here, we report the
purification of a P-TEFb complex fraction containing epitope-tagged wild-type
CDK9 or kinase-inactive CDK9 and five tightly associated polypeptides. Only wild
type P-TEFb complex with an active CDK9 kinase was able to hyperphosphorylate the
C-terminal domain of RNA polymerase II and mediate Tat transactivation in P-TEFb
depleted HeLa nuclear extract. Tat also stimulated transcription elongation by
recruitment of the P-TEFb complex to the HIV-1 promoter through a Tat-TAR
interaction. A possible mechanism for P-TEFb to become associated with polymerase
elongation complexes and function as a general elongation factor was demonstrated
by an interaction of P-TEFb with double-stranded RNA molecules through an 87 kDa
subunit. Finally, P-TEFb was found to interact with and phosphorylate Tat-SF1, a
Tat cofactor required for Tat transactivation. Our data indicate that the various
subunits of the human P-TEFb complex may play distinct roles at multiple stages
to mediate Tat activation of HIV-1 transcription elongation.
PMID- 9649439
TI - A specialized form of RNA polymerase I, essential for initiation and growth
dependent regulation of rRNA synthesis, is disrupted during transcription.
AB - Only a small proportion (<2%) of RNA polymerase I (pol I) from whole-cell
extracts appeared to be competent for specific initiation at the ribosomal gene
promoter in a yeast reconstituted transcription system. Initiation-competent pol
I molecules were found exclusively in salt-resistant complexes that contain the
pol I-specific initiation factor Rrn3p. Levels of initiation-competent complexes
in extracts were independent of total Rrn3p content and varied with the growth
state of the cells. Although extracts from stationary phase cells contained
substantial amounts of Rrn3p and pol I, they lacked the pol I-Rrn3p complex and
were inactive in promoter-dependent transcription. Activity was restored by
adding purified pol I-Rrn3p complex to extracts from stationary phase cells. The
pol I-Rrn3p complex dissociated during transcription and lost its capacity for
subsequent reinitiation in vitro, suggesting a stoichiometric rather than a
catalytic activity in initiation. We propose that the formation and disruption of
the pol I-Rrn3p complex reflects a molecular switch for regulating rRNA synthesis
and its growth rate-dependent regulation.
PMID- 9649440
TI - Molecular mechanism of polyhomeotic activation by Engrailed.
AB - The Drosophila Engrailed homeoprotein has been shown to activate directly a
Polycomb-group gene, polyhomeotic, during embryogenesis. The molecular mechanism
involved in this activation has been studied. Two different types of Engrailed
binding fragments have been detected within the polyhomeotic locus. The P1 and D1
fragments contain several 'TTAATTGCAT' motifs, whereas the D2 fragment contains a
long 'TAAT' stretch to which multiple copies of Engrailed bind cooperatively.
Another homeodomain-containing protein, Extradenticle, establishes protein
protein interactions with Engrailed on the D2 fragment. We have shown by CAT
assays that both types of Engrailed-binding sites (P1 or D1 and D2), as well as
Extradenticle, are necessary to obtain activation by Engrailed. In vivo, we have
also shown that normal polyhomeotic expression depends on extradenticle
expression. Moreover, in the absence of Extradenticle, overexpression of
Engrailed protein represses polyhomeotic expression.
PMID- 9649441
TI - Hoxa9 transforms primary bone marrow cells through specific collaboration with
Meis1a but not Pbx1b.
AB - Hoxa9, Meis1 and Pbx1 encode homeodomaincontaining proteins implicated in
leukemic transformation in both mice and humans. Hoxa9, Meis1 and Pbx1 proteins
have been shown to physically interact with each other, as Hoxa9 cooperatively
binds consensus DNA sequences with Meis1 and with Pbx1, while Meis1 and Pbx1 form
heterodimers in both the presence and absence of DNA. In this study, we sought to
determine if Hoxa9 could transform hemopoietic cells in collaboration with either
Pbx1 or Meis1. Primary bone marrow cells, retrovirally engineered to overexpress
Hoxa9 and Meis1a simultaneously, induced growth factor-dependent oligoclonal
acute myeloid leukemia in <3 months when transplanted into syngenic mice. In
contrast, overexpression of Hoxa9, Meis1a or Pbx1b alone, or the combination of
Hoxa9 and Pbx1b failed to transform these cells acutely within 6 months post
transplantation. Similar results were obtained when FDC-P1 cells, engineered to
overexpress these genes, were transplanted to syngenic recipients. Thus, these
studies demonstrate a selective collaboration between a member of the Hox family
and one of its DNA-binding partners in transformation of hemopoietic cells.
PMID- 9649442
TI - Processing of a dicistronic small nucleolar RNA precursor by the RNA endonuclease
Rnt1.
AB - Small nucleolar RNAs (snoRNAs) are intron encoded or expressed from monocistronic
independent transcription units, or, in the case of plants, from polycistronic
clusters. We show that the snR190 and U14 snoRNAs from the yeast Saccharomyces
cerevisiae are co-transcribed as a dicistronic precursor which is processed by
the RNA endonuclease Rnt1, the yeast ortholog of bacterial RNase III. RNT1
disruption results in a dramatic decrease in the levels of mature U14 and snR190
and in accumulation of dicistronic snR190-U14 RNAs. Addition of recombinant Rnt1
to yeast extracts made from RNT1 disruptants induces the chase of dicistronic
RNAs into mature snoRNAs, showing that dicistronic RNAs correspond to functional
precursors stalled in the processing pathway. Rnt1 cleaves a dicistronic
transcript in vitro in the absence of other factors, separating snR190 from U14.
Thus, one of the functions of eukaryotic RNase III is, as for the bacterial
enzyme, to liberate monocistronic RNAs from polycistronic transcripts.
PMID- 9649443
TI - Depletion of yeast RNase III blocks correct U2 3' end formation and results in
polyadenylated but functional U2 snRNA.
AB - Yeast U2 snRNA is transcribed by RNA polymerase II to generate a single non
polyadenylated transcript. A temperature-sensitive yeast strain carrying a
disruption in RNT1, the gene encoding a homolog of RNase III, produces 3'
extended U2 that is polyadenylated. The U2 3'-flanking region contains a putative
stem-loop that is recognized and cleaved at two sites by recombinant GST-Rnt1
protein in vitro. Removal of sequences comprising the stem-loop structure blocks
cleavage in vitro and mimics the effects of Rnt1 depletion in vivo. Strains
carrying a U2 gene lacking the Rnt1 cleavage site produce only polyadenylated U2
snRNA, and yet are not impaired in growth or splicing. The results suggest that
eukaryotic RNase III may be a general factor in snRNA processing, and demonstrate
that polyadenylation is not incompatible with snRNA function in yeast.
PMID- 9649444
TI - The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA
synthesis and localization.
AB - Most small nucleolar RNAs (snoRNAs) fall into two families, known as the box C/D
and box H/ACA snoRNAs. The various box elements are essential for snoRNA
production and for snoRNA-directed modification of rRNA nucleotides. In the case
of the box C/D snoRNAs, boxes C and D and an adjoining stem form a vital
structure, known as the box C/D motif. Here, we examined expression of natural
and artificial box C/D snoRNAs in yeast and mammalian cells, to assess the role
of the box C/D motif in snoRNA localization. The results demonstrate that the
motif is necessary and sufficient for nucleolar targeting, both in yeast and
mammals. Moreover, in mammalian cells, RNA is targeted to coiled bodies as well.
Thus, the box C/D motif is the first intranuclear RNA trafficking signal
identified for an RNA family. Remarkably, it also couples snoRNA localization
with synthesis and, most likely, function. The distribution of snoRNA precursors
in mammalian cells suggests that this coupling is provided by a specific
protein(s) which binds the box C/D motif during or rapidly after snoRNA
transcription. The conserved nature of the box C/D motif indicates that its role
in coupling production and localization of snoRNAs is of ancient evolutionary
origin.
PMID- 9649445
TI - lambda bar minigene-mediated inhibition of protein synthesis involves
accumulation of peptidyl-tRNA and starvation for tRNA.
AB - Expression of the bacteriophage lambda two-codon, AUG AUA, barI minigene (bar+)
leads to the arrest of protein synthesis in cells defective in peptidyl-tRNA
hydrolase (Pth). It has been hypothesized that translation of the bar+ transcript
provokes premature release and accumulation of peptidyl-tRNA (p-tRNA). Inhibition
of protein synthesis would then result from either starvation of sequestered tRNA
or from toxicity of accumulated p-tRNA. To test this hypothesis and to
investigate the cause of arrest, we used a coupled in vitro transcription
translation system primed with DNA containing bar+ and the beta-lactamase
encoding gene of the vector as a reporter. The results show that expression of
bar+ minigene severely inhibits beta-lactamase polypeptide synthesis by Pth
defective extracts and partially inhibits synthesis by wild-type extracts.
Fractions enriched for Pth, or a homogeneous preparation of Pth, prevented and
reversed bar+-mediated inhibition. A mutant minigene, barA702, which changes the
second codon AUA (Ile) to AAA (Lys), was also toxic for Pth-defective cells.
Expression of barA702 inhibited in vitro polypeptide synthesis by Pth-defective
extracts and, as with bar+, exogenous Pth prevented inhibition. Addition of pure
tRNALys prevented inhibition by barA702 but not by bar+. Expression of bar+ and
barA702 led to release and accumulation of p-tRNAIle and p-tRNALys respectively
but bar+ also induced accumulation of p-tRNALys. Finally, bar+ stimulated
association of methionine with ribosomes probably as fMet-tRNAfMet and the
accumulation of methionine and isoleucine in solution as peptidyl-tRNA (p-tRNA).
These results indicate that minigene-mediated inhibition of protein synthesis
involves premature release of p-tRNA, misincorporation of amino acyl-tRNA,
accumulation of p-tRNAs and possibly sequestration of tRNAs.
PMID- 9649446
TI - Identification of a sequence element immediately upstream of the polypurine tract
that is essential for replication of simian immunodeficiency virus.
AB - A short stretch of T-rich sequences immediately upstream of the polypurine tract
(PPT) is highly conserved in the proviral genomes of human and simian
immunodeficiency viruses (HIV and SIV). To investigate whether this 'U-box'
influences SIVmac239 replication, we analyzed the properties of mutants with
changes in this region of the viral genome. All mutants were either retarded in
their growth (up to one month delay) or did not replicate detectably in CEMx174
cells. When U-box mutants did replicate detectably, compensatory changes were
consistently observed in the viral genome. The most common compensatory change
was the acquisition of thymidines immediately upstream of the PPT, but marked
expansion in the length of the PPT was also observed. U-box mutants produced
transiently by transfection were severely impaired in their ability to produce
reverse transcripts in infectivity assays. Analysis of transiently produced
mutant virus revealed no defect in RNA packaging or virus assembly. These results
identify a new structural element important for an early step in the viral life
cycle that includes reverse transcription.
PMID- 9649447
TI - The same two monomers within a MuA tetramer provide the DDE domains for the
strand cleavage and strand transfer steps of transposition.
AB - The chemistry of Mu transposition is executed within a tetrameric form of the Mu
transposase (MuA protein). A triad of DDE (Asp, Asp35Glu motif) residues in the
central domain of MuA (DDE domain) is essential for both the strand cleavage and
strand transfer steps of transposition. Previous studies had suggested that
complete Mu transposition requires all four subunits in the MuA tetramer to carry
an active DDE domain. Using a mixture of MuA proteins with either wild-type or
altered att-DNA binding specificities, we have now designed specific arrangements
of MuA subunits carrying the DDE domain. From analysis of the abilities of
oriented tetramers to carry out DNA cleavage and strand transfer from supercoiled
DNA, a new picture of the disposition of DNA and protein partners during
transposition has emerged. For DNA cleavage, two subunits of MuA located at attL1
and attR1 (sites that undergo cleavage) provide DDE residues in trans. The same
two subunits contribute DDE residues for strand transfer, also in trans. Thus,
only two active DDE+ monomers within the tetramer carry out complete Mu
transposition. We also show that when the attR1-R2 arrangement used on
supercoiled substrates is tested for cleavage on linear substrates, alternative
chemically competent DNA-protein associations are produced, wherein the
functional DDE subunits are positioned at R2 rather than at R1.
PMID- 9649449
TI - CFTR: from scientific inquiry to clinical remedy.
PMID- 9649448
TI - DNA ligase I is recruited to sites of DNA replication by an interaction with
proliferating cell nuclear antigen: identification of a common targeting
mechanism for the assembly of replication factories.
AB - In mammalian cells, DNA replication occurs at discrete nuclear sites termed
replication factories. Here we demonstrate that DNA ligase I and the large
subunit of replication factor C (RF-C p140) have a homologous sequence of
approximately 20 amino acids at their N-termini that functions as a replication
factory targeting sequence (RFTS). This motif consists of two boxes: box 1
contains the sequence IxxFF whereas box 2 is rich in positively charged residues.
N-terminal fragments of DNA ligase I and the RF-C large subunit that contain the
RFTS both interact with proliferating cell nuclear antigen (PCNA) in vitro.
Moreover, the RFTS of DNA ligase I and of the RF-C large subunit is necessary and
sufficient for the interaction with PCNA. Both subnuclear targeting and PCNA
binding by the DNA ligase I RFTS are abolished by replacement of the adjacent
phenylalanine residues within box 1. Since sequences similar to the RFTS/PCNA
binding motif have been identified in other DNA replication enzymes and in
p21(CIP1/WAF1), we propose that, in addition to functioning as a DNA polymerase
processivity factor, PCNA plays a central role in the recruitment and stable
association of DNA replication proteins at replication factories.
PMID- 9649450
TI - Image of the month. Esophageal diverticulum.
PMID- 9649451
TI - Colonoscopic screening in first-degree relatives of patients with 'sporadic'
colorectal cancer: a case-control study. The Association Nationale des
Gastroenterologues des Hopitaux and Registre Bourguignon des Cancers Digestifs
(INSERM CRI 9505)
AB - BACKGROUND & AIMS: A screening policy has not been well defined in first-degree
relatives of patients with sporadic colorectal cancer. This study estimated the
risk of colorectal adenoma in a cohort of individuals with only 1 affected first
degree relative. METHODS: A total of 476 first-degree relatives (age, 40-74
years) of 195 patients with sporadic colorectal cancer were offered a
colonoscopy. Each examined relative was matched with 2 controls for age, sex,
symptoms, and center. The prevalence of colorectal adenomas was compared using a
multiple logistic regression analysis. RESULTS: In 185 relatives, odds ratios
were 1.5 (95% confidence interval [CI], 1.0-2.4) for adenomas, 2.5 for large
adenomas (95% CI, 1.1-5.4), 1.2 for small adenomas (95% CI, 0.7-1.9), and 2.6
(95% CI, 1.3-5.1) for high-risk adenomas (> or = 1 cm in size and/or with a
villous component). The prevalence of high-risk adenomas in relatives was higher
when the index patient was younger than 65 years, was male, and had distal rather
than proximal cancer. CONCLUSIONS: Subjects with only 1 affected first-degree
relative are at increased risk for developing large adenomas.
PMID- 9649452
TI - Cruveilhier of la maladie de Cruveilhier.
PMID- 9649453
TI - Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence
and characteristics at follow-up. The Polyp Prevention Study Group.
AB - BACKGROUND & AIMS: All patients with colorectal adenomas may not require
identical follow-up. We aimed to determine if adenoma characteristics at initial
colonoscopy could predict adenoma recurrence or characteristics at follow-up.
METHODS: The number of adenomas and the size, type, and degree of atypia in 479
patients in a polyp prevention trial were evaluated as predictors of the same
characteristics at follow-up using odds ratios (ORs) with 95% confidence
intervals (CIs). Multiple logistic regression analysis was performed to determine
if several baseline characteristics were simultaneously associated with outcome.
RESULTS: Although several characteristics were significant predictors of
recurrence univariately, by multivariate analysis, multiple adenomas at follow-up
were more likely when patients had > or = 3 baseline adenomas (OR, 2.25; 95% CI,
1.20-4.21) or at least 1 tubulovillous adenoma (OR, 2.12; 95% CI, 1.12-4.02). No
specific characteristic was associated with recurrence of high-risk polyps (> or
= 1 cm, villous, severe atypia). Seventy percent of patients with 1 or 2 baseline
adenomas had no recurrence, and only 3.3% had any adenomas of clinical concern.
CONCLUSIONS: Number and type of baseline adenomas predict recurrent adenomas, but
the recurrence is rarely of clinical concern. Patients with 1 or 2 tubular
adenomas constitute a low-risk group for whom follow-up might be extended beyond
3 years.
PMID- 9649454
TI - Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma
can predate cancer diagnosis.
AB - BACKGROUND & AIMS: We previously discovered anti-p53 antibodies predating a
cancer diagnosis in subjects at increased risk for liver, lung, breast, and
prostate cancer. Recently, we reported a significant correlation (P < 0.017)
between p53 antibodies and p53 mutations in patients with late-stage esophageal
carcinoma. Because others have reported p53 mutations and overexpression of p53
protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88
serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal
squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with
esophagitis or normal esophagus. METHODS: We used enzyme immunoassay,
immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase
chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53
mutations; and immunohistochemistry for p53 protein. RESULTS: p53 antibodies were
detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that
later progressed to adenocarcinoma, and in 10 cancer patients (P = 0.002) (8
squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had
antibodies before cancer was diagnosed. Other patient groups were too small for
informative statistical analysis. Six antibody-positive cancer patients had p53
mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with
antibodies had p53 protein overexpressed in esophageal tissues. CONCLUSIONS:
Patients with Barrett's esophagus and esophageal cancer can develop p53
antibodies that may predate the clinical diagnosis of malignancy.
PMID- 9649455
TI - Oral beclomethasone dipropionate for treatment of intestinal graft-versus-host
disease: a randomized, controlled trial.
AB - BACKGROUND & AIMS: Beclomethasone dipropionate (BDP), a topically active steroid,
seemed to be an effective treatment for intestinal graft-versus-host disease
(GVHD) in a phase I study. The aim of this study was to compare the effectiveness
of oral BDP to that of placebo capsules in treatment of intestinal GVHD. METHODS:
Sixty patients with anorexia and poor oral intake because of intestinal GVHD were
randomized to receive prednisone (1 mg.kg-1.day-1) plus either oral BDP (8
mg/day) or placebo capsules. Initial responders who were eating at least 70% of
caloric needs at evaluation on day 10 continued to take study capsules for an
additional 20 days while the prednisone dose was rapidly tapered. The primary end
point was the frequency of a durable treatment response at day 30 of treatment.
RESULTS: The initial treatment response at day 10 was 22 of 31 (71%) in the
BDP/prednisone group vs. 16 of 29 (55%) for the placebo/prednisone group. The
durable treatment response at day 30 was 22 of 31 (71%) vs. 12 of 29 (41%),
respectively (P = 0.02). CONCLUSIONS: The combination of oral BDP capsules and
prednisone was more effective than prednisone alone in treating intestinal GVHD.
Oral BDP allowed prednisone doses to be rapidly tapered without recurrent
intestinal symptoms.
PMID- 9649456
TI - Effect of a low-impact exercise program on bone mineral density in Crohn's
disease: a randomized controlled trial.
AB - BACKGROUND & AIMS: Physical exercise increases bone mineral density (BMD) in
healthy young adults and slows the rate of bone loss in later life. The aim of
this randomized controlled trial was to investigate the effect of exercise on BMD
in patients with Crohn's disease. METHODS: A total of 117 patients with Crohn's
disease were randomized to a control group or a low-impact exercise program of
increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the
hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS:
Nonsignificant gains in BMD occurred at the hip and spine in the exercise group
compared with controls (P > 0.05). In fully compliant patients, BMD increased by
3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at
Ward's triangle, and 7.77% (8.2%) at the greater trochanter. Compared with
controls, gain in BMD at the greater trochanter was statistically significant
(difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02).
Increases in BMD were significantly related to the number of exercise sessions
completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04).
CONCLUSIONS: Progressive low-impact exercise is a potentially effective method of
increasing BMD in Crohn's disease. If sustained, the increases in BMD may reduce
the risk of osteoporotic fracture.
PMID- 9649457
TI - The clinical and economic value of a short course of omeprazole in patients with
noncardiac chest pain.
AB - BACKGROUND & AIMS: Evaluation of new patients with noncardiac chest pain (NCCP)
may require a variety of costly tests. The aim of this study was to evaluate the
efficacy of the omeprazole test (OT) in diagnosing gastroesophageal reflux (GERD)
in patients with NCCP and estimate the potential cost savings of this strategy
compared with conventional diagnostic evaluations. METHODS: Thirty-nine patients
referred by cardiologists were enrolled. Baseline symptoms were recorded, and the
patients were randomized to either placebo or omeprazole (40 mg AM and 20 mg PM)
groups for 7 days. Patients were crossed over to the other arm after a washout
period and repeat baseline symptom assessment. All patients underwent 24-hour
esophageal pH monitoring and upper endoscopy before randomization. RESULTS:
Thirty-seven patients (94.9%) completed the study. Twenty-three (62.2%) were
classified as GERD positive and 14 as GERD negative. Eighteen (78%) GERD-positive
patients and 2 (14%) GERD-negative patients had a positive OT (P < 0.01),
yielding a sensitivity of 78.3% (95% confidence interval, 61.4-95.1) and
specificity of 85.7% (95% confidence interval, 67.4-100). Economic analysis
showed that the OT saves $573 per average patient evaluated and results in a 59%
reduction in the number of diagnostic procedures. CONCLUSIONS: The OT is
sensitive and specific for diagnosing GERD in patients with NCCP. This strategy
results in significant cost savings and decreased use of diagnostic tests.
PMID- 9649458
TI - The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum
of gastroesophageal reflux disease.
AB - BACKGROUND & AIMS: The role of Helicobacter pylori in the pathogenesis of
gastroesophageal reflux disease (GERD) is unknown. We determined the prevalence
of cagA-positive (cagA+) H. pylori strains in patients with GERD or its
complications compared with controls of similar age. METHODS: A total of 153
consecutive patients with GERD, Barrett's esophagus, and Barrett's esophagus
complicated by dysplasia or adenocarcinoma were compared with 57 controls who
underwent upper endoscopy for reasons other than GERD. H. pylori infection and
CagA antibody status were determined by histology and enzyme-linked immunosorbent
assay. RESULTS: H. pylori prevalence was lower (34%) in patients with GERD and
its sequelae than in the control group (45.6%)(P = 0.15). Regardless of the
group, increasing age was associated with higher prevalence of H. pylori (P =
0.003). When compared with controls (42.3%), the prevalence of cagA+ H. pylori
strains decreased (P = 0.008) in patients with more severe complications of GERD
(GERD, 36.7% [nonerosive GERD, 41.2%; erosive GERD, 30.8%]; Barrett's esophagus,
13.3%; and Barrett's with adenocarcinoma/dysplasia, 0%). CONCLUSIONS: Prevalence
of H. pylori in patients with GERD and its sequelae was lower but not
significantly different than that of a control group. However, patients carrying
cagA+ strains of H. pylori may be protected against the complications of GERD,
especially Barrett's esophagus and its associated dysplasia and adenocarcinoma.
PMID- 9649459
TI - Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori.
AB - BACKGROUND & AIMS: Clinical outcome of Helicobacter pylori infection may be
associated with specific virulence-associated bacterial genotypes. The aim of
this study was to assess the relationships between H. pylori cagA, vacA, and iceA
status and severity of disease. METHODS: Gastric biopsy specimens from 94
patients in The Netherlands were analyzed by polymerase chain reaction and
reverse hybridization. RESULTS: cagA was present in 63 (67%) of 94 cases and was
associated with peptic ulcer disease (P = 0.0019). vacA geno-types s1a/m1,
s1b/m2, s1b/m1, s1b/m2, and s2/m2 were found in 36.2%, 23.4%, 2.1%, 5.3%, and
20.2%, respectively. Ten isolates (10.6%) contained multiple vacA genotypes. The
presence of peptic ulcers was associated with type s1 strains (P = 0.0006) but
not with the m type (P = 0.2035). cagA and vacA s1 were strongly associated (P <
10(-5)). iceA1 was found in 53 (56.4%) and iceA2 in 25 (26.6%) of the 94 cases.
In 14 isolates (14.9%), both iceA alleles were found, and 2 (2.1%) were negative
for both iceA1 and iceA2. iceA1 was also associated with peptic ulcer disease (P
= 0.0042). The iceA allelic type was independent of the cagA and vacA status.
CONCLUSIONS: vacA s1, cagA, and iceA1 are markers of H. pylori strains that are
more likely to lead to ulcer disease.
PMID- 9649460
TI - The effect of tacrolimus (FK506) on intestinal barrier function and cellular
energy production in humans.
AB - BACKGROUND & AIMS: The maintenance of the intestinal mucosal barrier may be
energy dependent. Tacrolimus is a potent immunosuppressive drug that decreases
mitochondrial adenosine triphosphate production and increases intestinal
permeability in animals. METHODS: Twelve liver graft recipients receiving
tacrolimus, 9 healthy volunteers, and 5 liver graft recipients not receiving
immunosuppression underwent a combined absorption-permeability-mitochondrial
function test using 5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O
methyl-D-glucose, 1 mg/kg 2-keto[1-13C]isocaproic acid ([13C]KICA), and 20 mg/kg
L-leucine. The respiratory quotient and resting energy expenditure were measured
by indirect calorimetry. Tacrolimus pharmacokinetic profiles and levels of
endotoxin and IgM and IgG endotoxin core antibodies were determined. RESULTS:
Tacrolimus inhibited the decarboxylation of [13C]KICA, the resting energy
expenditure, and the respiratory quotient in an exposure-dependent manner,
suggesting an inhibition of mitochondrial respiration. Tacrolimus inhibited
intestinal absorptive capacity in an exposure-dependent manner. Tacrolimus
treated patients had an increased intestinal permeability and significantly
higher endotoxin levels compared with healthy volunteers. CONCLUSIONS: Tacrolimus
inhibits cellular energy production in humans at clinically relevant doses. This
is associated with an increased intestinal permeability, endotoxemia, and an
impaired intestinal absorptive capacity.
PMID- 9649461
TI - Colonocyte differentiation is associated with increased expression and altered
distribution of protein kinase C isozymes.
AB - BACKGROUND & AIMS: Colon cancer cells express reduced levels of protein kinase C
(PKC). This study examines the regulation of PKC isozymes in normal colonic
epithelium, as a basis for understanding the significance of alterations in this
enzyme system in colon carcinogenesis. METHODS: The expression and localization
of PKC isozymes in mouse and rat colonocytes at different developmental stages
were determined using a combined morphological and biochemical approach. PKC
alpha expression was compared in colonic adenocarcinomas and adjacent normal
mucosa by immunoblot analysis. RESULTS: Mouse and rat colonocytes express PKC
alpha, beta II, delta, epsilon, and zeta. Relatively low levels of these isozymes
were detected in proliferating cells of the crypt base, predominantly in the
cytosolic compartment. Coincident with colonocyte growth arrest/differentiation,
PKC isozyme expression markedly increased in both the cytosolic and, more
significantly, in the membrane/cytoskeletal fraction. Colonic tumors express
reduced levels of PKC alpha, an isozyme that has been implicated in negative
control of intestinal cell growth. CONCLUSIONS: These findings are supportive of
a role for certain PKC isozyme(s) in signaling pathways mediating postmitotic
events in colonocytes in situ, and suggest that diminished activity of these
pathway(s) may contribute to the alterations in growth control/differentiation
associated with colonic neoplasia.
PMID- 9649462
TI - Three distinct messenger RNA distribution patterns in human jejunal enterocytes.
AB - BACKGROUND & AIMS: The importance of messenger RNA (mRNA) localization in human
enterocytes is poorly understood. Previous studies from our laboratory have
indicated that mRNAs are asymmetrically distributed in human intestinal
epithelial cells, but in general colocalized with their encoded proteins. The aim
of this study was to characterize, in human enterocytes, mRNA localization
patterns of three genes with distinctly different functions. METHODS: mRNA
distribution was determined by in situ hybridization with digoxigenin-labeled RNA
probes in tissue sections of human jejunum. RESULTS: The mRNA for villin, a well
characterized microvillus cytoskeletal protein, was sorted to the basal region of
the enterocyte. The mRNA for human sodium glucose cotransporter 1 was localized
to the apical region, and the mRNA for human liver fatty acid-binding protein was
distributed diffusely in the cytoplasm. CONCLUSIONS: The three distinct mRNA
distribution patterns suggest that active mRNA sorting mechanisms exist in human
enterocytes. This study also reveals for the first time that dichotomies may
occur between the distribution patterns of sorted mRNAs and their encoded
proteins.
PMID- 9649463
TI - Comparison of the signal transduction pathways activated by gastrin in
enterochromaffin-like and parietal cells.
AB - BACKGROUND & AIMS: Gastrin stimulates acid secretion from parietal cells and
histamine release from enterochromaffin-like (ECL) cells through identical
gastrin receptors. However, gastrin has been shown to have a trophic effect only
on ECL cells. The aim of this study was to compare gastrin-induced signal
transduction pathways in the ECL and parietal cells of Mastomys natalensis, an
African rodent. METHODS: Both ECL and parietal cells were isolated from the
gastric mucosa of M. natalensis, and intracellular signal transduction events in
response to gastrin were investigated. RESULTS: Gastrin elicited histamine
release from ECL cells and acid secretion from parietal cells in association with
enhanced inositol phospholipid turnover. Although gastrin increased [3H]thymidine
incorporation into ECL cells, it had no effect on parietal cells. Moreover,
tyrosine phosphorylation and activation of mitogen-activated protein (MAP) kinase
as well as c-fos and c-jun gene expression were augmented only in ECL cells. In
addition, gastrin increased the formation of guanosine triphosphate-Ras with a
simultaneous decrease in guanosine diphosphate-Ras levels in ECL but not in
parietal cells. CONCLUSIONS: Although gastrin receptors are present in both ECL
and parietal cells, they activate the Ras-MAP kinase pathway only in ECL cells.
PMID- 9649464
TI - Cyclooxygenase 1 contributes to inflammatory responses in rats and mice:
implications for gastrointestinal toxicity.
AB - BACKGROUND & AIMS: Selective inhibitors of cyclooxygenase (COX)-2 are being
developed as gastrointestinal-sparing anti-inflammatory drugs based on the
premise that this isoform is solely responsible for prostaglandin synthesis at
sites of inflammation, whereas COX-1 produces prostaglandins important for
maintenance of mucosal integrity. We investigated the relationship between
suppression of inflammation by COX-2 inhibitors (NS-398, nimesulide, DuP697, and
etodolac) and their effects on gastric prostaglandin synthesis. METHODS: Effects
of pretreatment of rats with drugs with a range of in vitro selectivity for COX-2
vs. COX-1 on carrageenan-induced paw inflammation were assessed, along with
extent of suppression of COX-1 and COX-2. The role of COX-1 in inflammation was
also assessed in COX-2-deficient mice. RESULTS: Significant anti-inflammatory
effects were only observed at doses of the drugs that inhibited COX-1. At these
doses, the drugs also significantly suppressed gastric prostaglandin synthesis
and elicited gastric mucosal erosions. The degree of suppression of prostaglandin
synthesis at the site of inflammation correlated significantly with inhibition of
COX-1 but not COX-2. CONCLUSIONS: COX-1 makes an important contribution to
inflammatory responses. To achieve desirable anti-inflammatory effects, COX-2
inhibitors needed to be given at doses in which selectivity was lost, leading to
suppression of gastric prostaglandin synthesis and to mucosal injury.
PMID- 9649465
TI - Vegetative infection of transjugular intrahepatic portosystemic shunts.
AB - BACKGROUND & AIMS: The occurrence of and the clinical picture of infection of
transjugular intrahepatic portosystemic shunts (TIPS) has not been described
previously. We describe the clinical features, associated pathogens, results of
treatment of a previously unreported complication of TIPS, and primary infection
of TIPS occurring after formation of the neointima. METHODS: Patients with TIPS
and fever were evaluated to exclude other sources of infection. The diagnosis was
based on the occurrence of fever with positive blood cultures and either a
thrombus or vegetations on the stent or persistent bacteremia in a patient with a
TIPS and no other detectable source of infection despite an extensive search.
RESULTS: Eight patients met diagnostic criteria. Two of 8 cases occurred within
10 days of TIPS manipulation despite antibiotic administration before the
procedure. The clinical features included fever (8 patients), tender hepatomegaly
(5 of 8), hypoxemia (2 of 8), septic pulmonary emboli (1 of 8), septic shock (2
of 8), neutrophilia (5 of 8), and subsequent development of necrotizing fasciitis
(1 of 8). Blood cultures were positive in all cases. The organisms included oral
and enteric aerobic gram-negative bacteria in 7 of 8 patients and Candida in 1
patient. All 8 responded to administration of antibiotics. Two patients died of
myocardial infarction and alcoholic hepatitis, respectively. CONCLUSIONS:
Infective endotipsitis is an uncommon complication of TIPS. Recognition of its
clinical features will facilitate diagnosis. Most patients responded to
antibiotic therapy.
PMID- 9649466
TI - Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate
in the treatment of portal hypertension.
AB - BACKGROUND & AIMS: The association of prazosin to propranolol enhances the
decrease in portal pressure but may cause hypotension and sodium retention. The
aim of this study was to compare the portal pressure reduction and safety of the
combination of propranolol plus prazosin with that of propranolol plus isosorbide
5-mononitrate (ISMN). METHODS: Fifty-six portal-hypertensive cirrhotics received
randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28)
orally for 3 months. Hemodynamics and liver and renal function were assessed at
baseline and after 3 months. RESULTS: Propranolol plus prazosin caused a greater
reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (
24.2% +/- 11% vs. -16.1% +/- 11%; P < 0.01). A reduction in HVPG of > 20% was
significantly more frequent in the propranolol plus prazosin group than in the
propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified
hepatic blood flow, quantitative liver function test results, glomerular
filtration rate, plasma renin activity, or plasma aldosterone level. Side effects
occurred in 13 patients receiving propranolol plus prazosin compared with 7
receiving propranolol plus ISMN (P = 0.16). CONCLUSIONS: Propranolol plus
prazosin has a greater portal pressure-lowering effect than propranolol plus
ISMN. Both therapies were safe for liver and renal function. However, the
combination of propranolol plus prazosin caused a greater decrease in arterial
pressure and was less well tolerated than propranolol plus ISMN.
PMID- 9649467
TI - Bile lithogenicity and gallbladder emptying in patients with microlithiasis:
effect of bile acid therapy.
AB - BACKGROUND & AIMS: Biliary cholesterol supersaturation, rapid nucleation of
cholesterol, and altered gallbladder motility are prerequisite for gallstone
formation. However, the pathogenesis of microlithiasis is not clear. The aim of
this study was to determine the abnormalities of gallbladder emptying and bile
composition in patients with microlithiasis. METHODS: Nucleation time,
cholesterol saturation index (CSI), and gallbladder emptying were studied in
patients with microlithiasis (n = 10), patients with gallstones (n = 10), and
healthy volunteers (n = 10). Bile analysis was repeated in 6 patients with
microlithiasis treated with ursodeoxycholic acid (UDCA) for 8 weeks. RESULTS:
Nucleation time was shorter in patients with microlithiasis and those with
gallstones than in healthy volunteers (P < 0.0001). Patients with microlithiasis
had longer nucleation time than those with gallstones (P < 0.001). There was no
difference in cholesterol levels and CSI in gallstone and microlithiasis
patients. However, healthy volunteers had lower cholesterol levels (P < 0.01) and
CSI (P < 0.01). Patients with microlithiasis had prolongation of nucleation time
(P < 0.001) and lowering of CSI (P < 0.001) after UDCA therapy. Gallbladder
ejection fraction was higher in microlithiasis patients than in gallstone
patients (P < 0.01) but lower than in healthy volunteers (P < 0.01). CONCLUSIONS:
Patients with microlithiasis have longer nucleation time and better gallbladder
emptying than patients with gallstones. Bile abnormalities can be successfully
corrected with UDCA therapy in patients with microlithiasis.
PMID- 9649468
TI - Biliary secretory immunoglobulin A is a major constituent of the new group of
cholesterol crystal-binding proteins.
AB - BACKGROUND & AIMS: Recently we described a new group of lectin-bound biliary
proteins that bind to cholesterol crystals, modify crystal morphology, and
inhibit cholesterol crystallization. The aim of the current study was to
characterize and identify individual members of this group of cholesterol crystal
binding proteins. METHODS: Crystal-binding proteins were purified from human
gallbladder bile by lectin affinity chromatography and preparative gel
electrophoresis. Purified crystal-binding proteins were characterized by using
cholesterol crystal-growth assays, immunoblotting, and amino acid analysis. For
comparison, identified biliary proteins were isolated from gallbladder bile by
lectin affinity and immunoaffinity chromatography. RESULTS: The individual
crystal-binding proteins with molecular weights of 74, 63, and 28 kilodaltons
inhibited cholesterol crystallization in a dose-dependent manner (2.5-10
micrograms/mL). Immunoblotting with specific antibodies and N-terminal amino acid
sequences revealed that the 74-kilodalton crystal-binding protein is the
secretory component, the 63-kilodalton protein is the heavy chain, and the 28
kilodalton protein is the light chain of human secretory immunoglobulin (Ig) A.
Isolated biliary IgA showed a potent inhibitory effect on cholesterol
crystallization in model bile even at levels less than physiological
concentrations (1-100 micrograms/mL). CONCLUSIONS: Biliary secretory IgA is a
major constituent of the previously described group of cholesterol crystal
binding proteins. Crystal-binding IgA may be an important modulator of crystal
agglomeration into stones and stone growth in vivo.
PMID- 9649469
TI - Three-dimensional structure of the major autoantigen in primary biliary
cirrhosis.
AB - BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver
disease characterized by the presence of antimitochondrial autoantibodies in
patients' serum. The major autoantigen, recognized by antibodies from > 95% of
patients with PBC, has been identified as the E2 component (E2p) of the pyruvate
dehydrogenase multienzyme complex. Immunodominant sites on E2p have been
localized to the inner of the two lipoyl domains, where the essential cofactor
lipoic acid is attached covalently. The aim of this study was to determine the
three-dimensional structure of the inner lipoyl domain of human E2p. METHODS: The
domain was expressed in Escherichia coli; after purification, its structure was
analyzed using nuclear magnetic resonance spectroscopy. RESULTS: The structure of
the lipoyl domain from human E2p was determined, and the implications of the
structure for autoimmune recognition were assessed. CONCLUSIONS: Knowledge of the
structure further defines the major epitope and may help in the design of antigen
specific immunotherapy for treatment of PBC.
PMID- 9649470
TI - Altered biosynthesis of leukotrienes and lipoxins and host defense disorders in
patients with cirrhosis and ascites.
AB - BACKGROUND & AIMS: Advanced cirrhosis is associated with impaired leukocyte
function, but the mechanism underlying this host defense alteration is unknown.
The aim of this study was to investigate the lipoxygenase pathway of arachidonic
acid metabolism and its influence in leukocyte trafficking in patients with
cirrhosis and ascites. METHODS: Neutrophils (polymorphonuclear leukocytes [PMN])
were isolated from patients with cirrhosis and ascites and healthy subjects, and
5-lipoxygenase (5-LO) messenger RNA levels and 5-LO-derived products were
measured. The effect of leukotrienes (LT) and lipoxins (LX) on PMN adhesion and
migration was also assessed. RESULTS: PMN from patients with cirrhosis showed
increased 5-LO messenger RNA expression. However, in vitro generation of LTB4,
cysteinyl-containing LT and LX was significantly decreased in cirrhotic patients.
Interestingly, a close relationship between the activity of the renin-angiotensin
system and LXA4 biosynthesis was observed both in vitro and in vivo. PMN isolated
from cirrhotic patients with ascites showed significantly decreased adhesion and
migration in response to LTB4. LXA4 did not provoke PMN adhesion and migration,
but rather abrogated the differences between control and cirrhotic PMN. Cirrhotic
monocytes showed marked impairment in adherence to laminin when stimulated with
either LTB4 or LXA4. CONCLUSIONS: These results show the existence of altered
biosynthesis of LT and LX and defective response to these lipoxygenase products
in leukocytes from patients with cirrhosis and ascites. This abnormality may be
relevant to the pathogenesis of host defense disorders in chronic liver disease.
PMID- 9649471
TI - Role of cytokines in ethanol-induced cytotoxicity in vitro in Hep G2 cells.
AB - BACKGROUND & AIMS: As shown previously by us, ethanol (EtOH) causes time- and
concentration-dependent reduction in cytoviability. Tauroursodeoxycholic acid
(TUDCA) and ursodeoxycholic acid (UDCA) were shown to reduce cytotoxicity. Long
term EtOH exposure leads to immunoregulatory and detoxification impairment. This
study aimed to determine the relationship between cytokine (interleukin [IL]-1
alpha and IL-6 and tumor necrosis factor [TNF]-alpha) production and expression,
glutathione (GSH) status, and EtOH-induced cytotoxicity on Hep G2 cells. METHODS:
Cells were incubated with 80 mmol/L EtOH or alpha-minimal essential medium
(control) in the presence or absence of 50 mumol/L TUDCA or UDCA. Cytokine
release was quantitated by enzyme-linked immunosorbent assay. Cytokine expression
was measured by reverse-transcription polymerase chain reaction. GSH content was
determined in both the cytosolic and mitochondrial fractions. RESULTS: After 24
hours of EtOH exposure, the release of IL-1 alpha doubled, that of IL-6 increased
10 times, and that of TNF-alpha increased 3.5 times. Cytokine expression was up
regulated compared with control for IL-1 alpha (42%), IL-6 (26%), and TNF-alpha
(52%). Addition of 50 mumol/L TUDCA or UDCA reduced cytokine release and
expression. TNF-alpha increased cytotoxicity by 18%. Anti-TNF-alpha antibody
almost abolished it. EtOH depleted mGSH levels by 55% (P < 0.001). TUDCA
replenished them by 88%. CONCLUSIONS: EtOH up-regulated expression of cytokines
in Hep G2 cells is down-regulated by bile acids. Increased amounts of TNF-alpha
and depletion in both cytosolic and mitochondrial GSH contribute to EtOH
cytotoxicity. Bile acids prevent toxicity.
PMID- 9649472
TI - Transjugular intrahepatic portosystemic shunt for bleeding angiodysplasia-like
lesions in portal-hypertensive colopathy.
AB - Portal-hypertensive colopathy has attracted interest in recent years because such
lesions can cause life-threatening hemorrhage. In contrast to upper
gastrointestinal bleeding from varices, there is no established therapy for
bleeding from angiodysplasia-like lesions. This case report describes the first
successful use of transjugular intrahepatic portosystemic shunt (TIPS) for long
term control of bleeding from angiodysplasia-like colonic lesions in a patient
with cirrhosis caused by chronic hepatitis B infection. During an 18-month course
after TIPS, angiodysplasia-like lesions disappeared without any further evidence
of recurrent hematochezia. TIPS may be helpful as second-line treatment in
patients with recurrent portal-hypertensive bleeding from colonic angiodysplasia
like lesions who do not tolerate or are unresponsive to treatment with beta
adrenergic blockers.
PMID- 9649473
TI - Overexpression of an unstable intrinsic factor-cobalamin receptor in Imerslund
Grasbeck syndrome.
AB - Two sisters with Imerslund-Grasbeck syndrome who presented with clinical features
of cobalamin deficiency are described. Intrinsic factor-cobalamin receptor (IFCR)
activity and protein levels were determined in ileal biopsy specimens by using
radioisotope assay and immunoblotting, respectively. IFCR activities in ileal
homogenates expressed as femtomoles of ligand binding per milligram of protein
were 38 +/- 4 in control tissue, 494 +/- 24 in patient 1, and 94 +/- 7 in patient
2. However, when assayed in the presence of IFCR antiserum, the ligand binding
was inhibited by > 90% in both normal control and the patients with Imerslund
Grasbeck syndrome. Immunoblotting of total membranes from the biopsy specimen of
these 2 patients failed to detect an immunoreactive band of molecular mass of 185
kilodaltons. These findings are at variance with reports of decreased IFCR
activity and indicate a new phenotype in which an active but an unstable receptor
is overexpressed in Imerslund-Grasbeck syndrome.
PMID- 9649474
TI - Treatment of fibrosing cholestatic hepatitis with lamivudine.
AB - Fibrosing cholestatic hepatitis is a histological variant of hepatitis B virus
infection with a high rate of mortality. We describe a patient who acquired acute
hepatitis B virus infection 8 months after renal transplantation. Clinical
features of rapidly progressive liver failure, indicated by prolonged prothrombin
time (57 seconds) and increased bilirubin (40.4 mg/dL) and ammonia (129 mumol/L)
concentrations, were accompanied by an extremely high serum HBV DNA level (2.153
x 10(6) pg/mL). Liver biopsy specimen showed fibrosing cholestatic hepatitis with
widespread balloon degeneration of hepatocytes, focal hepatocyte loss, bile
stasis, periportal fibrosis, mild lymphocytic infiltration, and strongly positive
immunohistochemical staining for hepatitis B surface antigen (HBsAg) and
hepatitis B core antigen. Lamivudine therapy suppressed HBV DNA to < 10 pg/mL
within 4 weeks, which was followed by gradual recovery of liver function from a
state of hepatic precoma. Twenty-four months after the onset of hepatitis, the
patient had normal prothrombin time and bilirubin, transaminase, and albumin
levels. She remained HBsAg positive and hepatitis B e antigen negative. Renal
allograft function was stable, with a creatinine level of 1.52 mg/dL. HBV DNA
remained suppressed after 22 months of lamivudine therapy. Our experience shows
that fibrosing cholestatic hepatitis and liver failure caused by HBV infection
can be successfully treated with lamivudine.
PMID- 9649475
TI - Inflammatory bowel disease: etiology and pathogenesis.
PMID- 9649476
TI - The pathogenesis of celiac disease.
PMID- 9649477
TI - Diagnosis of celiac sprue.
PMID- 9649478
TI - Gastroenterology and hepatology look to the future.
PMID- 9649479
TI - Intestinal graft-versus-host disease.
PMID- 9649480
TI - The acid suppression test for unexplained chest pain.
PMID- 9649481
TI - PKC isoforms: villains in colon cancer?
PMID- 9649482
TI - Selective COX-2 inhibitors: are they safe for the stomach?
PMID- 9649483
TI - Blocking the bleeding way.
PMID- 9649484
TI - Enteropathogenic E. coli: intimacy redefined.
PMID- 9649485
TI - Less than an ounce of prevention.
PMID- 9649486
TI - Association of primary sclerosing cholangitis and colorectal cancer in patients
with ulcerative colitis: is it true and does it matter?
PMID- 9649488
TI - Unintentional Gluten Ingestion in Celiac Patients.
PMID- 9649487
TI - Pancreatoduodenectomy for chronic pancreatitis.
PMID- 9649489
TI - Insensitivity of the CLOtest for H. pylori, Especially in the Elderly.
PMID- 9649491
TI - The Relevance of Luminal Release Is Doubtful.
PMID- 9649490
TI - HCV NS5A mutations in Europeans infected by genotype 1b.
PMID- 9649492
TI - Histamine H3 Receptors and Gastric Acid Secretion.
PMID- 9649493
TI - Benefits of colorectal cancer patient follow-up.
PMID- 9649494
TI - Surveillance after colorectal cancer: the final word?
PMID- 9649495
TI - Follow-up after curative resection for colorectal cancer.
PMID- 9649496
TI - Image of the Month Answer.
PMID- 9649497
TI - Groucho proteins: transcriptional corepressors for specific subsets of DNA
binding transcription factors in vertebrates and invertebrates.
PMID- 9649498
TI - Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress.
AB - The initiation of apoptosis often transpires in the presence of agents that
regulate cell survival. This study evaluated the effects of stress-induced
ceramide on the anti-apoptotic activity of the phosphoinositide-3 kinase [PI(3)K]
pathway. PI(3)K activity is directly down-regulated by stress-induced ceramide in
a dose-dependent manner with rapid kinetics and high specificity. Ceramide
inhibition of PI(3)K is dependent on acid-sphingomyelinase. Down-regulation of
PI(3)K by ceramide results in inhibition of the kinase Akt and decreased
phosphorylation of the death effector Bad. Thus, ceramide levels could act as a
general apoptotic rheostat controlling cell survival by regulating PI(3)K anti
apoptotic effector mechanisms.
PMID- 9649499
TI - pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis
elegans.
AB - To build complex organs, embryos have evolved mechanisms that integrate the
development of cells unrelated to one another by cell type or ancestry. Here we
show that the pha-4 locus establishes organ identity for the Caenorhabditis
elegans pharynx. In pha-4 mutants, pharyngeal cells are transformed into
ectoderm. Conversely, ectopic pha-4 expression produces excess pharyngeal cells.
pha-4 encodes an HNF-3 homolog selectively expressed in the nascent digestive
tract, including all pharynx precursors at the time they are restricted to a
pharyngeal fate. We suggest that pha-4 is a key component of a transcription
based mechanism to endow cells with pharyngeal organ identity.
PMID- 9649500
TI - Antigen receptor signaling induces MAP kinase-mediated phosphorylation and
degradation of the BCL-6 transcription factor.
AB - The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor
expressed in germinal center (GC) B and T cells and required for GC formation and
antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal
rearrangements and point mutations of the bcl-6 promoter region are implicated in
the pathogenesis of B-cell lymphoma. The signals regulating bcl-6 expression are
not known. Here we show that antigen receptor activation leads to BCL-6
phosphorylation by mitogen-activated protein kinase (MAPK). Phosphorylation, in
turn, targets BCL-6 for rapid degradation by the ubiquitin/proteasome pathway.
These findings indicate that BCL-6 expression is directly controlled by the
antigen receptor via MAPK activation. This signaling pathway may be crucial for
the control of B-cell differentiation and antibody response and has implications
for the regulation of other POZ/zinc finger transcription factors in other
tissues.
PMID- 9649501
TI - Negative regulation of the heat shock transcriptional response by HSBP1.
AB - In response to stress, heat shock factor 1 (HSF1) acquires rapid DNA binding and
transient transcriptional activity while undergoing conformational transition
from an inert non-DNA-binding monomer to active functional trimers. Attenuation
of the inducible transcriptional response occurs during heat shock or upon
recovery at non-stress conditions and involves dissociation of the HSF1 trimer
and loss of activity. We have used the hydrophobic repeats of the HSF1
trimerization domain in the yeast two-hybrid protein interaction assay to
identify heat shock factor binding protein 1 (HSBP1), a novel, conserved, 76
amino-acid protein that contains two extended arrays of hydrophobic repeats that
interact with the HSF1 heptad repeats. HSBP1 is nuclear-localized and interacts
in vivo with the active trimeric state of HSF1 that appears during heat shock.
During attenuation of HSF1 to the inert monomer, HSBP1 associates with Hsp70.
HSBP1 negatively affects HSF1 DNA-binding activity, and overexpression of HSBP1
in mammalian cells represses the transactivation activity of HSF1. To establish a
biological role for HSBP1, the homologous Caenorhabditis elegans protein was
overexpressed in body wall muscle cells and was shown to block activation of the
heat shock response from a heat shock promoter-reporter construct. Alteration in
the level of HSBP1 expression in C. elegans has severe effects on survival of the
animals after thermal and chemical stress, consistent with a role for HSBP1 as a
negative regulator of the heat shock response.
PMID- 9649502
TI - Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53
apoptotic function.
AB - The p53 tumor suppressor gene product interacts with the p300 transcriptional
coactivator that regulates the transactivation of p53-inducible genes. The
adenovirus E1A protein has been shown to bind to p300 and inhibit its function.
E1A inhibits p53 transactivation and also promotes p53 accumulation by a p300
dependent mechanism. Murine double minute 2 (Mdm2) is a transcriptional target of
p53 that binds to p53 and inhibits its transcriptional activity. E1A inhibited
mdm2 transactivation without affecting the expression of p21(WAF1) or Bax, which
resulted in high levels of p53 accumulation and apoptosis. Ectopic expression of
p300 restored Mdm2 levels and inhibited p53-dependent apoptosis, as did ectopic
expression of Mdm2. Thus, p300 is required for mdm2 induction by p53 and the
subsequent inhibition of p53 stabilization. Inhibition of p300 by E1A results in
stabilization of p53 and causes apoptosis. Moreover, E1B 19K or Bcl-2 expression
in E1A-transformed cells abrogated p53-dependent apoptosis by restoring mdm2
transactivation by p53. Hence, p300 regulation of mdm2 expression controls
apoptotic activity of p53, and 19K or Bcl-2 bypass E1A inhibition of p300
transactivation of Mdm2.
PMID- 9649503
TI - Identification of Xenopus SMC protein complexes required for sister chromatid
cohesion.
AB - The structural maintenance of chromosomes (SMC) family is a growing family of
chromosomal ATPases. The founding class of SMC protein complexes, condensins,
plays a central role in mitotic chromosome condensation. We report here a new
class of SMC protein complexes containing XSMC1 and XSMC3, Xenopus homologs of
yeast Smc1p and Smc3p, respectively. The protein complexes (termed cohesins)
exist as two major forms with sedimentation coefficients of 9S and 14S. 9S
cohesin is a heterodimer of XSMC1 and XSMC3, whereas 14S cohesin contains three
additional subunits. One of them has been identified as a Xenopus homolog of the
Schizosaccharomyces pombe Rad21p implicated in DNA repair and the Saccharomyces
cerevisiae Scc1p/Mcd1p implicated in sister chromatid cohesion. 14S cohesin binds
to interphase chromatin independently of DNA replication and dissociates from it
at the onset of mitosis. Immunodepletion of cohesins during interphase causes
defects in sister chromatid cohesion in subsequent mitosis, whereas condensation
is unaffected. These results suggest that proper assembly of mitotic chromosomes
is regulated by two distinct classes of SMC protein complexes, cohesins and
condensins.
PMID- 9649504
TI - Identification of functional exonic splicing enhancer motifs recognized by
individual SR proteins.
AB - Using an in vitro randomization and functional selection procedure, we have
identified three novel classes of exonic splicing enhancers (ESEs) recognized by
human SF2/ASF, SRp40, and SRp55, respectively. These ESEs are functional in
splicing and are highly specific. For SF2/ASF and SRp55, in most cases, only the
cognate SR protein can efficiently recognize an ESE and activate splicing. In
contrast, the SRp40-selected ESEs can function with either SRp40 or SRp55, but
not with SF2/ASF. UV cross-linking/competition and immunoprecipitation
experiments showed that SR proteins recognize their cognate ESEs in nuclear
extract by direct and specific binding. A motif search algorithm was used to
derive consensus sequences for ESEs recognized by these SR proteins. Each SR
protein yielded a distinct 5- to 7-nucleotide degenerate consensus. These three
consensus sequences occur at higher frequencies in exons than in introns and may
thus help define exon-intron boundaries. They occur in clusters within regions
corresponding to naturally occurring, mapped ESEs. We conclude that a remarkably
diverse set of sequences can function as ESEs. The degeneracy of these motifs is
consistent with the fact that exonic enhancers evolved within extremely diverse
protein coding sequences and are recognized by a small number of SR proteins that
bind RNA with limited sequence specificity.
PMID- 9649505
TI - The ROOT HAIRLESS 1 gene encodes a nuclear protein required for root hair
initiation in Arabidopsis.
AB - The epidermis of Arabidopsis wild-type primary roots, in which some cells grow
hairs and others remain hairless in a position-dependent manner, has become an
established model system to study cell differentiation. Here we present a
molecular analysis of the RHL1 (ROOT HAIRLESS 1) gene that, if mutated, prevents
the formation of hairs on primary roots and causes a seedling lethal phenotype.
We have cloned the RHL1 gene by use of a T-DNA-tagged mutant and found that it
encodes a protein that appears to be plant specific. The predicted RHL1 gene
product is a small hydrophilic protein (38.9 kD) containing putative nuclear
localization signals and shows no significant homology to any known amino acid
sequence. We demonstrate that a 78-amino-acid sequence at its amino terminus is
capable of directing an RHL1-GFP fusion protein to the nucleus. The RHL1
transcript is present throughout the wild-type plant and in suspension culture
cells, but in very low amounts, suggesting a regulatory function for the RHL1
protein. Structural evidence suggests a role for the RHL1 gene product in the
nucleolus. We have examined the genetic relationship between RHL1 and GL2, an
inhibitor of root hair initiation in non-hair cells. Our molecular and genetic
data with double mutants, together with the expression analysis of a GL2 promoter
GUS reporter gene construct, indicate that the RHL1 gene acts independently of
GL2.
PMID- 9649506
TI - Functional intertwining of Dpp and EGFR signaling during Drosophila endoderm
induction.
AB - Endoderm induction in Drosophila is mediated by the extracellular signals
Decapentaplegic (Dpp) and Wingless (Wg). We discovered a secondary signal with a
permissive role in this process, namely Vein, a neuregulin-like ligand that
stimulates the epidermal growth factor receptor (EGFR) and Ras signaling. Dpp and
Wg up-regulate vein expression in the midgut mesoderm in two regions overlapping
the Dpp sources. Experiments based on lack of function and ectopic stimulation of
Dpp and EGFR signaling show that these two pathways are functionally
interdependent and that they synergize with each other, revealing functional
intertwining. The transcriptional response elements for the Dpp signal in midgut
enhancers from homeotic target genes are bipartite, comprising CRE sites as well
as binding sites for the Dpp signal-transducing protein Mad. Of these sites, the
CRE seems to function primarily in the response to Ras, the secondary signal of
Dpp. We discuss the potential significance of why an inductive process might use
a secondary signal whose function is intertwined with that of the primary signal.
PMID- 9649507
TI - Proneural gene self-stimulation in neural precursors: an essential mechanism for
sense organ development that is regulated by Notch signaling.
AB - To learn about the acquisition of neural fate by ectodermal cells, we have
analyzed a very early sign of neural commitment in Drosophila, namely the
specific accumulation of achaete-scute complex (AS-C) proneural proteins in the
cell that becomes a sensory organ mother cell (SMC). We have characterized an AS
C enhancer that directs expression specifically in SMCs. This enhancer promotes
Scute protein accumulation in these cells, an event essential for sensory organ
development in the absence of other AS-C genes. Interspecific sequence
comparisons and site-directed mutagenesis show the presence of several conserved
motifs necessary for enhancer action, some of them binding sites for proneural
proteins. These and other data indicate that the enhancer mediates scute self
stimulation, although only in the presence of additional activating factors,
which most likely interact with conserved motifs reminiscent of NF-kappaB-binding
sites. Cells neighboring the SMC do not acquire the neural fate because the Notch
signaling pathway effectors, the Enhancer of split bHLH proteins, block this
proneural gene self-stimulatory loop, possibly by antagonizing the action on the
enhancer of the NF-kappaB-like factors or the proneural proteins. These data
suggest a mechanism for SMC committment.
PMID- 9649508
TI - Self-renewal of pluripotent embryonic stem cells is mediated via activation of
STAT3.
AB - The propagation of embryonic stem (ES) cells in an undifferentiated pluripotent
state is dependent on leukemia inhibitory factor (LIF) or related cytokines.
These factors act through receptor complexes containing the signal transducer
gp130. The downstream mechanisms that lead to ES cell self-renewal have not been
delineated, however. In this study, chimeric receptors were introduced into ES
cells. Biochemical and functional studies of transfected cells demonstrated a
requirement for engagement and activation of the latent trancription factor
STAT3. Detailed mutational analyses unexpectedly revealed that the four STAT3
docking sites in gp130 are not functionally equivalent. The role of STAT3 was
then investigated using the dominant interfering mutant, STAT3F. ES cells that
expressed this molecule constitutively could not be isolated. An episomal
supertransfection strategy was therefore used to enable the consequences of
STAT3F expression to be examined. In addition, an inducible STAT3F transgene was
generated. In both cases, expression of STAT3F in ES cells growing in the
presence of LIF specifically abrogated self-renewal and promoted differentiation.
These complementary approaches establish that STAT3 plays a central role in the
maintenance of the pluripotential stem cell phenotype. This contrasts with the
involvement of STAT3 in the induction of differentiation in somatic cell types.
Cell type-specific interpretation of STAT3 activation thus appears to be pivotal
to the diverse developmental effects of the LIF family of cytokines.
Identification of STAT3 as a key transcriptional determinant of ES cell self
renewal represents a first step in the molecular characterization of
pluripotency.
PMID- 9649509
TI - Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3
and inhibits its transcriptional activity.
AB - Interferon regulatory factor-3 (IRF-3) was found to specifically interact with
HPV16 E6 in a yeast two-hybrid screen. IRF-3 is activated by the presence of
double-stranded RNA or by virus infection to form a stable complex with other
transcriptional regulators that bind to the regulatory elements of the IFNbeta
promoter. We show that IRF-3 is a potent transcriptional activator and
demonstrate that HPV16 E6 can inhibit its transactivation function. The
expression of HPV16 E6 in primary human keratinocytes inhibits the induction of
IFNbeta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3
does not result in its ubiquitination or degradation. We propose that the
interaction of E6 with IRF-3 and the inhibition of IRF-3's transcriptional
activity may provide the virus a means to circumvent the normal antiviral
response of an HPV16-infected cell.
PMID- 9649510
TI - New POU dimer configuration mediates antagonistic control of an osteopontin
preimplantation enhancer by Oct-4 and Sox-2.
AB - The POU transcription factor Oct-4 is expressed specifically in the germ line,
pluripotent cells of the pregastrulation embryo and stem cell lines derived from
the early embryo. Osteopontin (OPN) is a protein secreted by cells of the
preimplantation embryo and contains a GRGDS motif that can bind to specific
integrin subtypes and modulate cell adhesion/migration. We show that Oct-4 and
OPN are coexpressed in the preimplantation mouse embryo and during
differentiation of embryonal cell lines. Immunoprecipitation of the first intron
of OPN (i-opn) from covalently fixed chromatin of embryonal stem cells by Oct-4
specific antibodies indicates that Oct-4 binds to this fragment in vivo. The i
opn fragment functions as an enhancer in cell lines that resemble cells of the
preimplantation embryo. Furthermore, it contains a novel palindromic Oct factor
recognition element (PORE) that is composed of an inverted pair of homeodomain
binding sites separated by exactly 5 bp (ATTTG +5 CAAAT). POU proteins can homo-
and heterodimerize on the PORE in a configuration that has not been described
previously. Strong transcriptional activation of the OPN element requires an
intact PORE. In contrast, the canonical octamer overlapping with the downstream
half of the PORE is not essential. Sox-2 is a transcription factor that contains
an HMG box and is coexpressed with Oct-4 in the early mouse embryo. Sox-2
represses Oct-4 mediated activation of i-opn by way of a canonical Sox element
that is located close to the PORE. Repression depends on a carboxy-terminal
region of Sox-2 that is outside of the HMG box. Expression, DNA binding, and
transactivation data are consistent with the hypothesis that OPN expression is
regulated by Oct-4 and Sox-2 in preimplantation development.
PMID- 9649511
TI - The language of gene interaction.
PMID- 9649512
TI - UV light induces IS10 transposition in Escherichia coli.
AB - A new mutagenesis assay system based on the phage 434 cI gene carried on a low
copy number plasmid was used to investigate the effect of UV light on
intermolecular transposition of IS10. Inactivation of the target gene by IS10
insertion was detected by the expression of the tet gene from the phage 434 PR
promoter, followed by Southern blot analysis of plasmids isolated from TetR
colonies. UV irradiation of cells harboring the target plasmid and a donor
plasmid carrying an IS10 element led to an increase of up to 28-fold in IS10
transposition. Each UV-induced transposition of IS10 was accompanied by fusion of
the donor and acceptor plasmid into a cointegrate structure, due to coupled
homologous recombination at the insertion site, similar to the situation in
spontaneous IS10 transposition. UV radiation also induced transposition of IS10
from the chromosome to the target plasmid, leading almost exclusively to the
integration of the target plasmid into the chromosome. UV induction of IS10
transposition did not depend on the umuC and uvrA gene product, but it was not
observed in lexA3 and DeltarecA strains, indicating that the SOS stress response
is involved in regulating UV-induced transposition. IS10 transposition, known to
increase the fitness of Escherichia coli, may have been recruited under the SOS
response to assist in increasing cell survival under hostile environmental
conditions. To our knowledge, this is the first report on the induction of
transposition by a DNA-damaging agent and the SOS stress response in bacteria.
PMID- 9649513
TI - Salmonella virulence plasmid. Modular acquisition of the spv virulence region by
an F-plasmid in Salmonella enterica subspecies I and insertion into the
chromosome of subspecies II, IIIa, IV and VII isolates.
AB - The spv operon is common to all Salmonella virulence plasmids. DNA hybridization
analysis indicates that the spv region is limited in distribution to serovars of
Salmonella enterica subspecies I, II, IIIa, IV, and VII and is absent from
Salmonella bongori isolates. Among strains of subspecies II, IIIa, and VII, all
isolates examined contained sequences that hybridized with the spv region.
However, among isolates of subspecies I, DNA sequences capable of hybridizing
with the spv region were found in some isolates of certain serovars. Furthermore,
in isolates of subspecies I, the virulence plasmid was found in the same set of
isolates as an F-related plasmid, as determined by the presence of the spv region
of the virulence plasmid and the finO, traD, and repA sequences of the F-plasmid.
The concordance of the virulence plasmid and all three F-plasmid sequences in
subspecies I serovar Choleraesuis, Paratyphi, and Typhimurium is most easily
explained if the spv region is carried in an F-related plasmid in these isolates.
In contrast, among S. enterica subspecies II, IIIa, IV, and VII, the isolates
that contain spv sequences did not hybridize with an F-related plasmid or any
other identifiable plasmid. With the use of pulse-field gel electrophoresis, the
spv region in subspecies II, IIIa, and VII was found to be encoded on the
chromosome. Analysis of the phylogenetic distribution of spv among Salmonella
isolates and comparative nucleotide sequence analysis of spvA and spvC suggests
that the spv region was acquired very recently, after speciation of the
salmonellae.
PMID- 9649514
TI - The M26 hotspot of Schizosaccharomyces pombe stimulates meiotic ectopic
recombination and chromosomal rearrangements.
AB - Homologous recombination is increased during meiosis between DNA sequences at the
same chromosomal position (allelic recombination) and at different chromosomal
positions (ectopic recombination). Recombination hotspots are important elements
in controlling meiotic allelic recombination. We have used artificially dispersed
copies of the ade6 gene in Schizosaccharomyces pombe to study hotspot activity in
meiotic ectopic recombination. Ectopic recombination was reduced 10-1000-fold
relative to allelic recombination, and was similar to the low frequency of
ectopic recombination between naturally repeated sequences in S. pombe. The M26
hotspot was active in ectopic recombination in some, but not all, integration
sites, with the same pattern of activity and inactivity in ectopic and allelic
recombination. Crossing over in ectopic recombination, resulting in chromosomal
rearrangements, was associated with 35-60% of recombination events and was
stimulated 12-fold by M26. These results suggest overlap in the mechanisms of
ectopic and allelic recombination and indicate that hotspots can stimulate
chromosomal rearrangements.
PMID- 9649515
TI - Distribution of a limited Sir2 protein pool regulates the strength of yeast rDNA
silencing and is modulated by Sir4p.
AB - Transcriptional silencing in Saccharomyces cerevisiae occurs at the silent mating
type loci HML and HMR, at telomeres, and at the ribosomal DNA (rDNA) locus RDN1.
Silencing in the rDNA occurs by a novel mechanism that depends on a single Silent
Information Regulator (SIR) gene, SIR2. SIR4, essential for other silenced loci,
paradoxically inhibits rDNA silencing. In this study, we elucidate a regulatory
mechanism for rDNA silencing based on the finding that rDNA silencing strength
directly correlates with cellular Sir2 protein levels. The endogenous level of
Sir2p was shown to be limiting for rDNA silencing. Furthermore, small changes in
Sir2p levels altered rDNA silencing strength. In rDNA silencing phenotypes, sir2
mutations were shown to be epistatic to sir4 mutations, indicating that SIR4
inhibition of rDNA silencing is mediated through SIR2. Furthermore, rDNA
silencing is insensitive to SIR3 overexpression, but is severely reduced by
overexpression of full-length Sir4p or a fragment of Sir4p that interacts with
Sir2p. This negative effect of SIR4 overexpression was overridden by co
overexpression of SIR2, suggesting that SIR4 directly inhibits the rDNA silencing
function of SIR2. Finally, genetic manipulations of SIR4 previously shown to
promote extended life span also resulted in enhanced rDNA silencing. We propose a
simple model in which telomeres act as regulators of rDNA silencing by competing
for limiting amounts of Sir2 protein.
PMID- 9649516
TI - Fission yeast cdc24(+) encodes a novel replication factor required for chromosome
integrity.
AB - A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified
previously in a screen for cell division cycle mutants and the cdc24(+) gene was
determined to be essential for S phase in this yeast. We have isolated the
cdc24(+) gene by complementation of a new temperature-sensitive allele of the
gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame
punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null
mutant was generated by homologous recombination. Haploid cells lacking cdc24(+)
are inviable, indicating that cdc24(+) is an essential gene. The transcript of
cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking
cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content,
indicating a block late in S phase. Arrest is accompanied by a rapid loss of
viability and chromosome breakage. An S. pombe homolog of the replicative DNA
helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that
Cdc24p plays a role in the progression of normal DNA replication and is required
to maintain genomic integrity.
PMID- 9649517
TI - Effects of DNA double-strand and single-strand breaks on intrachromosomal
recombination events in cell-cycle-arrested yeast cells.
AB - Intrachromosomal recombination between repeated elements can result in deletion
(DEL recombination) events. We investigated the inducibility of such
intrachromosomal recombination events at different stages of the cell cycle and
the nature of the primary DNA lesions capable of initiating these events. Two
genetic systems were constructed in Saccharomyces cerevisiae that select for DEL
recombination events between duplicated alleles of CDC28 and TUB2. We determined
effects of double-strand breaks (DSBs) and single-strand breaks (SSBs) between
the duplicated alleles on DEL recombination when induced in dividing cells or
cells arrested in G1 or G2. Site-specific DSBs and SSBs were produced by
overexpression of the I-Sce I endonuclease and the gene II protein (gIIp),
respectively. I-Sce I-induced DSBs caused an increase in DEL recombination
frequencies in both dividing and cell-cycle-arrested cells, indicating that G1-
and G2-arrested cells are capable of completing DSB repair. In contrast, gIIp
induced SSBs caused an increase in DEL recombination frequency only in dividing
cells. To further examine these phenomena we used both gamma-irradiation,
inducing DSBs as its most relevant lesion, and UV, inducing other forms of DNA
damage. UV irradiation did not increase DEL recombination frequencies in G1 or
G2, whereas gamma-rays increased DEL recombination frequencies in both phases.
Both forms of radiation, however, induced DEL recombination in dividing cells.
The results suggest that DSBs but not SSBs induce DEL recombination, probably via
the single-strand annealing pathway. Further, DSBs in dividing cells may result
from the replication of a UV or SSB-damaged template. Alternatively, UV induced
events may occur by replication slippage after DNA polymerase pausing in front of
the damage.
PMID- 9649518
TI - A screen for genes involved in the anaphase proteolytic pathway identifies
tsm1(+), a novel Schizosaccharomyces pombe gene important for microtubule
integrity.
AB - The growth of several mitotic mutants of Schizosaccharomyces pombe, including
nuc2-663, is inhibited by the protease inhibitor N-Tosyl-L-Phenylalanine
Chloromethyl Ketone (TPCK). Because nuc2(+) encodes a presumptive component of
the Anaphase Promoting Complex, which is required for the ubiquitin-dependent
proteolysis of certain proteins during exit from mitosis, we have used
sensitivity to TPCK as a criterion by which to search for novel S. pombe mutants
defective in the anaphase-promoting pathway. In a genetic screen for temperature
sensitive mitotic mutants that were also sensitive to TPCK at a permissive
temperature, we isolated three tsm (TPCK-sensitive mitotic) strains. Two of these
are alleles of cut1(+), but tsm1-512 maps to a novel genetic location. The tsm1
512 mutation leads to delayed nuclear division at restrictive temperatures,
apparently as a result of an impaired ability to form a metaphase spindle. After
shift of early G2 cells to 36 degrees, tsm1-512 arrests transiently in the second
mitotic division and then exits mitosis, as judged by spindle elongation and
septation. The chromosomes, however, often fail to segregate properly. Genetic
interactions between tsm1-512 and components of the anaphase proteolytic pathway
suggest a functional involvement of the Tsm1 protein in this pathway.
PMID- 9649519
TI - Isolation and characterization of new fission yeast cytokinesis mutants.
AB - Schizosaccharomyces pombe is an excellent organism in which to study cytokinesis
as it divides by medial fission using an F-actin contractile ring. To enhance our
understanding of the cell division process, a large genetic screen was carried
out in which 17 genetic loci essential for cytokinesis were identified, 5 of
which are novel. Mutants identifying three genes, rng3(+), rng4(+), and rng5(+),
were defective in organizing an actin contractile ring. Four mutants defective in
septum deposition, septum initiation defective (sid)1, sid2, sid3, and sid4, were
also identified and characterized. Genetic analyses revealed that the sid mutants
display strong negative interactions with the previously described septation
mutants cdc7-24, cdc11-123, and cdc14-118. The rng5(+), sid2(+), and sid3(+)
genes were cloned and shown to encode Myo2p (a myosin heavy chain), a protein
kinase related to budding yeast Dbf2p, and Spg1p, a GTP binding protein that is a
member of the ras superfamily of GTPases, respectively. The ability of Spg1p to
promote septum formation from any point in the cell cycle depends on the activity
of Sid4p. In addition, we have characterized a phenotype that has not been
described previously in cytokinesis mutants, namely the failure to reorganize
actin patches to the medial region of the cell in preparation for septum
formation.
PMID- 9649520
TI - The PBN1 gene of Saccharomyces cerevisiae: an essential gene that is required for
the post-translational processing of the protease B precursor.
AB - The vacuolar hydrolase protease B in Saccharomyces cerevisiae is synthesized as
an inactive precursor (Prb1p). The precursor undergoes post-translational
modifications while transiting the secretory pathway. In addition to N- and O
linked glycosylations, four proteolytic cleavages occur during the maturation of
Prb1p. Removal of the signal peptide by signal peptidase and the autocatalytic
cleavage of the large amino-terminal propeptide occur in the endoplasmic
reticulum (ER). Two carboxy-terminal cleavages of the post regions occur in the
vacuole: the first cleavage is catalyzed by protease A and the second results
from autocatalysis. We have isolated a mutant, pbn1-1, that exhibits a defect in
the ER processing of Prb1p. The autocatalytic cleavage of the propeptide from
Prb1p does not occur and Prb1p is rapidly degraded in the cytosol. PBN1 was
cloned and is identical to YCL052c on chromosome III. PBN1 is an essential gene
that encodes a novel protein. Pbn1p is predicted to contain a sub-C-terminal
transmembrane domain but no signal sequence. A functional HA epitope-tagged Pbn1p
fusion localizes to the ER. Pbn1p is N-glycosylated in its amino-terminal domain,
indicating a lumenal orientation despite the lack of a signal sequence. Based on
these results, we propose that one of the functions of Pbn1p is to aid in the
autocatalytic processing of Prb1p.
PMID- 9649521
TI - Tip loci: six Chlamydomonas nuclear suppressors that permit the translocation of
proteins with mutant thylakoid signal sequences.
AB - Mutations within the signal sequence of cytochrome f (cytf) in Chlamydomonas
inhibit thylakoid membrane protein translocation and render cells
nonphotosynthetic. Twenty-seven suppressors of the mutant signal sequences were
selected for their ability to restore photoautotrophic growth and these describe
six nuclear loci named tip1 through 6 for thylakoid insertion protein. The tip
mutations restore the translocation of cytf and are not allele specific, as they
suppress a number of different cytf signal sequence mutations. Tip5 and 2 may act
early in cytf translocation, while Tip1, 3, 4, and 6 are engaged later. The tip
mutations have no phenotype in the absence of a signal sequence mutation and
there is genetic interaction between tip4, and tip5 suggesting an interaction of
their encoded proteins. As there is overlap in the energetic, biochemical and
genetic requirements for the translocation of nuclear and chloroplast-encoded
thylakoid proteins, the tip mutations likely identify components of a general
thylakoid protein translocation apparatus.
PMID- 9649522
TI - A genetic screen for temperature-sensitive cell-division mutants of
Caenorhabditis elegans.
AB - A novel screen to isolate conditional cell-division mutants in Caenorhabditis
elegans has been developed. The screen is based on the phenotypes associated with
existing cell-division mutations: some disrupt postembryonic divisions and affect
formation of the gonad and ventral nerve cord-resulting in sterile, uncoordinated
animals-while others affect embryonic divisions and result in lethality. We
obtained 19 conditional mutants that displayed these phenotypes when shifted to
the restrictive temperature at the appropriate developmental stage. Eighteen of
these mutations have been mapped; 17 proved to be single alleles of newly
identified genes, while 1 proved to be an allele of a previously identified gene.
Genetic tests on the embryonic lethal phenotypes indicated that for 13 genes,
embryogenesis required maternal expression, while for 6, zygotic expression could
suffice. In all cases, maternal expression of wild-type activity was found to be
largely sufficient for embryogenesis. Cytological analysis revealed that 10
mutants possessed embryonic cell-division defects, including failure to properly
segregate DNA, failure to assemble a mitotic spindle, late cytokinesis defects,
prolonged cell cycles, and improperly oriented mitotic spindles. We conclude that
this approach can be used to identify mutations that affect various aspects of
the cell-division cycle.
PMID- 9649523
TI - A new marker for mosaic analysis in Caenorhabditis elegans indicates a fusion
between hyp6 and hyp7, two major components of the hypodermis.
AB - A fusion of the sur-5 protein to the green fluorescent protein containing a
nuclear localization signal is demonstrated as a marker for genetic mosaic
analysis in the nematode Caenorhabditis elegans. Because of an extensive
accumulation of bright fluorescence in many nuclei, normal growth plates, each
containing hundreds of worms, can be rapidly screened with a dissecting
microscope for rare mosaic individuals. As the marker can also be used to detect
transgenic worms, the construction of strains for mosaic analyses can be
minimized. In the course of examining rare mosaic animals, an unexpected pattern
of fluorescence was noticed for hyp6, a syncytial component of the hypodermis,
which indicated that the marker may serve as a means of assessing cellular
fusions during development. Immunofluorescent staining of adherens junctions
confirmed a postembryonic fusion of hyp6 with hyp7, the major syncytium of the
hypodermis.
PMID- 9649524
TI - Identification of heterochronic mutants in Caenorhabditis elegans. Temporal
misexpression of a collagen::green fluorescent protein fusion gene.
AB - The heterochronic genes lin-4, lin-14, lin-28, and lin-29 specify the timing of
lateral hypodermal seam cell terminal differentiation in Caenorhabditis elegans.
We devised a screen to identify additional genes involved in this developmental
timing mechanism based on identification of mutants that exhibit temporal
misexpression from the col-19 promoter, a downstream target of the heterochronic
gene pathway. We fused the col-19 promoter to the green fluorescent protein gene
(gfp) and demonstrated that hypodermal expression of the fusion gene is adult
specific in wild-type animals and temporally regulated by the heterochronic gene
pathway. We generated a transgenic strain in which the col-19::gfp fusion
construct is not expressed because of mutation of lin-4, which prevents seam cell
terminal differentiation. We have identified and characterized 26 mutations that
restore col-19::gfp expression in the lin-4 mutant background. Most of the
mutations also restore other aspects of the seam cell terminal differentiation
program that are defective in lin-4 mutant animals. Twelve mutations are alleles
of three previously identified genes known to be required for proper timing of
hypodermal terminal differentiation. Among these are four new alleles of lin-42,
a heterochronic gene for which a single allele had been described previously. Two
mutations define a new gene, lin-58. When separated from lin-4, the lin-58
mutations cause precocious seam cell terminal differentiation and thus define a
new member of the heterochronic gene pathway.
PMID- 9649525
TI - Molecular evolution of a sex determination protein. FEM-2 (pp2c) in
Caenorhabditis.
AB - Somatic sex determination in Caenorhabditis elegans involves a signal
transduction pathway linking a membrane receptor to a transcription factor. The
fem-2 gene is central to this pathway, producing a protein phosphatase (FEM-2) of
the type 2C (PP2C). FEM-2 contains a long amino terminus that is absent in
canonical PP2C enzymes. The function of this domain is difficult to predict,
since it shows no sequence similarity to any other known proteins or motifs. Here
we report the cloning of the fem-2 homologue from Caenorhabditis briggsae (Cb-fem
2). The sequence identity is much higher than that observed for other C. briggsae
homologues of C. elegans sex determination proteins. However, this level is not
uniform across the entire lengths of the proteins; it is much lower in the amino
termini. Thus, the two domains of the same protein are evolving at different
rates, suggesting that they have different functional constraints. Consistent
with this, Cb-FEM-2 is able to replace some, but not all, of the Ce-FEM-2 in vivo
function. We show that removal of the amino terminus from Ce-FEM-2 has no effect
on its in vitro phosphatase activity, or its ability to replace the in vivo
function of a yeast PP2C enzyme, but that it is necessary for proper FEM-2
function in worms. This demonstrates that the amino terminus is not an extended
catalytic domain or a direct negative regulator of phosphatase activity.
PMID- 9649526
TI - The Y chromosomal fertility factor Threads in Drosophila hydei harbors a
functional gene encoding an axonemal dynein beta heavy chain protein.
AB - To understand the contradiction between megabase-sized lampbrush loops and
putative protein encoding genes both associated with the loci of Y chromosomal
fertility genes of Drosophila on the molecular level, we used PCR-mediated
cloning to identify and isolate the cDNA sequence of the Y chromosomal Drosophila
hydei gene DhDhc7(Y). Alignment of the sequences of the putative protein
DhDhc7(Y) and the outer arm dynein beta heavy chain protein DYH2 of Tripneustes
gratilla shows homology over the entire length of the protein chains. Therefore
the proteins can be assumed to fulfill orthologous functions within the sperm
tail axonemes of both species. Functional dynein beta heavy chain molecules,
however, are necessary for the assembly and attachment of outer dynein arms
within the sperm tail axoneme. Localization of DhDhc7(Y) to the fertility factor
Threads, comprising at least 5.1 Mb of transcriptionally active repetitive DNA,
results from an infertile Threads- mutant where large clusters of Threads
specifically transcribed satellites and parts of DhDhc7(Y) encoding sequences are
missing simultaneously. Consequently, the complete lack of the outer dynein arms
in Threads- males most probably causes sperm immotility and hence infertility of
the fly. Moreover, preliminary sequence analysis and several other features
support the hypothesis that DhDhc7(Y) on the lampbrush loops Threads in D. hydei
and Dhc-Yh3 on the lampbrush loops kl-5 in Drosophila melanogaster on the
heterochromatic Y chromosome of both species might indeed code for orthologous
dynein beta heavy chain proteins.
PMID- 9649527
TI - Mitochondrial DNA haplotype frequencies in natural and experimental populations
of Drosophila subobscura.
AB - The evolution of Drosophila subobscura mitochondrial DNA has been studied in
experimental populations, founded with flies from a natural population from
Esporles (Majorca, Balearic Islands, Spain). This population, like other European
ones, is characterized by the presence of two very common (>96%) mitochondrial
haplotypes (called I and II) and rare and endemic haplotypes that appear at very
low frequencies. There is no statistical evidence of positive Darwinian selection
acting on the mitochondrial DNA variants according to Tajima's neutrality test.
Two experimental populations, with one replicate each, were established with
flies having a heterogeneous nuclear genetic background, which was representative
of the composition of the natural population. Both populations were started with
the two most frequent mitochondrial haplotypes, but at different initial
frequencies. After 13 to 16 generations, haplotype II reached fixation in three
cages and its frequency was 0.89 by generation 25 in the fourth cage. Random
drift can be rejected as the force responsible for the observed changes in
haplotype frequencies. There is not only statistical evidence of a linear trend
favoring a mtDNA (haploid) fitness effect, but also of a significant nonlinear
deviation that could be due to a nuclear component.
PMID- 9649528
TI - Evaluating gene flow using selected markers: a case study.
AB - The extent to which an organism is locally adapted in an environmental pocket
depends on the selection intensities inside and outside the pocket, on migration,
and on the size of the pocket. When two or more loci are involved in this local
adaptation, measuring their frequency gradients and their linkage disequilbria
allows one to disentangle the forces-migration and selection-acting on the
system. We apply this method to the case of a local adaptation to organophosphate
insecticides in the mosquito Culex pipiens pipiens in southern France. The study
of two different resistance loci allowed us to estimate with support limits gene
flow as well as selection pressure on insecticide resistance and the fitness
costs associated with each locus. These estimates permit us to pinpoint the
conditions for the maintenance of this pocket of adaptation as well as the effect
of the interaction between the two resistance loci.
PMID- 9649529
TI - hobo Induced rearrangements in the yellow locus influence the insulation effect
of the gypsy su(Hw)-binding region in Drosophila melanogaster.
AB - The su(Hw) protein is responsible for the insulation mediated by the su(Hw)
binding region present in the gypsy retrotransposon. In the y2 mutant, su(Hw)
protein partially inhibits yellow transcription by repressing the function of
transcriptional enhancers located distally from the yellow promoter with respect
to gypsy. y2 mutation derivatives have been induced by the insertion of two hobo
copies on the both sides of gypsy: into the yellow intron and into the 5'
regulatory region upstream of the wing and body enhancers. The hobo elements have
the same structure and orientation, opposite to the direction of yellow
transcription. In the sequence context, where two copies of hobo are separated by
the su(Hw)-binding region, hobo-dependent rearrangements are frequently
associated with duplications of the region between the hobo elements. Duplication
of the su(Hw)-binding region strongly inhibits the insulation of the yellow
promoter separated from the body and wing enhancers by gypsy. These results
provide a better insight into mechanisms by which the su(Hw)-binding region
affects the enhancer function.
PMID- 9649530
TI - Courtship and visual defects of cacophony mutants reveal functional complexity of
a calcium-channel alpha1 subunit in Drosophila.
AB - We show by molecular analysis of behavioral and physiological mutants that the
Drosophila Dmca1A calcium-channel alpha1 subunit is encoded by the cacophony
(cac) gene and that nightblind-A and lethal(1)L13 mutations are allelic to cac
with respect to an expanded array of behavioral and physiological phenotypes
associated with this gene. The cacS mutant, which exhibits defects in the
patterning of courtship lovesong and a newly revealed but subtle abnormality in
visual physiology, is mutated such that a highly conserved phenylalanine (in one
of the quasi-homologous intrapolypeptide regions called IIIS6) is replaced by
isoleucine. The cacH18 mutant exhibits defects in visual physiology (including
complete unresponsiveness to light in certain genetic combinations) and visually
mediated behaviors; this mutant (originally nbAH18) has a stop codon in an
alternative exon (within the cac ORF), which is differentially expressed in the
eye. Analysis of the various courtship and visual phenotypes associated with this
array of cac mutants demonstrates that Dmca1A calcium channels mediate multiple,
separable biological functions; these correlate in part with transcript diversity
generated via alternative splicing.
PMID- 9649531
TI - Molecular screening for P-element insertions in a large genomic region of
Drosophila melanogaster using polymerase chain reaction mediated by the
vectorette.
AB - As an alternative to existing methods for the detection of new insertions during
a transposon mutagenesis, we adapted the method of vectorette ligation to genomic
restriction fragments followed by PCR to obtain genomic sequences flanking the
transposon. By combining flies containing a defined genomic transposon with an
excess of flies containing unrelated insertion sites, we demonstrate the
specificity and sensitivity of the procedure in the detection of integration
events. This method was applied in a transposon-tagging screen for BJ1, the
Drosophila homolog of the vertebrate gene Regulator of Chromosome Condensation
(RCCI). Genetic mobilization of a single genomic P element was used to generate
preferentially new local insertions from which integrations into a genomic region
surrounding the BJ1 gene were screened. Flies harboring new insertions were
phenotypically selected on the basis of the zeste1-dependent transvection of
white. We detected a single transposition to a 13-kb region close to the BJ1 gene
among 6650 progeny that were analyzed. Southern analysis of the homozygous line
confirmed the integration 3 kb downstream of BJ1.
PMID- 9649532
TI - Loss of notum macrochaetae as an interspecific hybrid anomaly between Drosophila
melanogaster and D. simulans.
AB - With the aim of revealing genetic variation accumulated among closely related
species during the course of evolution, this study focuses on loss of
macrochaetae on the notum as one of the developmental anomalies seen in
interspecific hybrids between Drosophila melanogaster and its closely related
species. Interspecific hybrids between a line of D. melanogaster and D. simulans
isofemale lines exhibited a wide range in the number of missing bristles. By
contrast, D. mauritiana and D. sechellia lines showed almost no reduction in
bristle number in hybrids with D. melanogaster. Genetic analysis showed that the
D. simulans X chromosome confers a large effect on hybrid bristle loss, although
X-autosome interaction may be involved. This suggests that at least one genetic
factor contributing to hybrid anomalies arose recently on a D. simulans X
chromosome. Moreover, the results indicate sex dependency: the male hybrids were
more susceptible to bristle loss than the female hybrids were. Use of cell type
markers suggests that the defect does not lie in cell fate decisions during
bristle development, but in the maintenance of neural fate and/or differentiation
of the descendants of sensory mother cells.
PMID- 9649533
TI - Chromosome rearrangements induce both variegated and reduced, uniform expression
of heterochromatic genes in a development-specific manner.
AB - In Drosophila melanogaster, chromosome rearrangements that juxtapose euchromatin
and heterochromatin can result in position effect variegation (PEV), the variable
expression of heterochromatic and euchromatic genes in the vicinity of the novel
breakpoint. We examined PEV of the heterochromatic light (lt) and concertina
(cta) genes in order to investigate potential tissue or developmental differences
in chromosome structure that might be informative for comparing the mechanisms of
PEV of heterochromatic and euchromatic genes. We employed tissue pigmentation and
in situ hybridization to RNA to assess expression of lt in individual cells of
multiple tissues during development. Variegation of lt was induced in the adult
eye, larval salivary glands and larval Malpighian tubules for each of three
different chromosome rearrangements. The relative severity of the effect in these
tissues was not tissue-specific but rather was characteristic of each
rearrangement. Surprisingly, larval imaginal discs did not exhibit variegated lt
expression. Instead, a uniform reduction of the lt transcript was observed, which
correlated in magnitude with the degree of variegation. The same results were
obtained for cta expression. These two distinct effects of rearrangements on
heterochromatic gene expression correlated with the developmental stage of the
tissue. These results have implications for models of heterochromatin formation
and the nuclear organization of chromosomes during development and
differentiation.
PMID- 9649534
TI - Drosophila hormone receptor 38 functions in metamorphosis: a role in adult
cuticle formation.
AB - DHR38 is a member of the steroid receptor superfamily in Drosophila homologous to
the vertebrate NGFI-B-type orphan receptors. In addition to binding to specific
response elements as a monomer, DHR38 interacts with the USP component of the
ecdysone receptor complex in vitro, in yeast and in a cell line, suggesting that
DHR38 might modulate ecdysone-triggered signals in the fly. We characterized the
molecular structure and expression of the Dhr38 gene and initiated an in vivo
analysis of its function(s) in development. The Dhr38 transcription unit spans
more than 40 kb in length, includes four introns, and produces at least four mRNA
isoforms differentially expressed in development; two of these are greatly
enriched in the pupal stage and encode nested polypeptides. We characterized four
alleles of Dhr38: a P-element enchancer trap line, l(2)02306, which shows
exclusively epidermal staining in the late larval, pre-pupal and pupal stages,
and three EMS-induced alleles. Dhr38 alleles cause localized fragility and
rupturing of the adult cuticle, demonstrating that Dhr38 plays an important role
in late stages of epidermal metamorphosis.
PMID- 9649535
TI - Autoregulation of transformer-2 alternative splicing is necessary for normal male
fertility in Drosophila.
AB - In the male germline of Drosophila the transformer-2 protein is required for
differential splicing of pre-mRNAs from the exuperantia and att genes and
autoregulates alternative splicing of its own pre-mRNA. Autoregulation of TRA-2
splicing results in production of two mRNAs that differ by the splicing/retention
of the M1 intron and encode functionally distinct protein isoforms. Splicing of
the intron produces an mRNA encoding TRA-2(226), which is necessary and
sufficient for both male fertility and regulation of downstream target RNAs. When
the intron is retained, an mRNA is produced encoding TRA-2(179), a protein with
no known function. We have previously shown that repression of M1 splicing is
dependent on TRA-2(226), suggesting that this protein quantitatively limits its
own expression through a negative feedback mechanism at the level of splicing.
Here we examine this idea, by testing the effect that variations in the level of
tra-2 expression have on the splicing of M1 and on male fertility. Consistent
with our hypothesis, we observe that as tra-2 gene dosage is increased, smaller
proportions of TRA-2(226) mRNA are produced, limiting expression of this isoform.
Feedback regulation is critical for male fertility, since it is significantly
decreased by a transgene in which repression of M1 splicing cannot occur and TRA
2(226) mRNA is constitutively produced. The effect of this transgene becomes more
severe as its dosage is increased, indicating that fertility is sensitive to an
excess of TRA-2(226). Our results suggest that autoregulation of TRA-2(226)
expression in male germ cells is necessary for normal spermatogenesis.
PMID- 9649536
TI - Female genotypes affect sperm displacement in Drosophila.
AB - Differential success of sperm is likely to be an important component of fitness.
Extensive variation among male genotypes in competitive success of sperm in
multiply mated females has been documented for Drosophila melanogaster. However,
virtually all previous studies considered the female to be a passive vessel.
Nevertheless, under certain conditions female fitness could be determined by her
role in mediating use of sperm from multiple males. Here we ask whether females
differ among genotypes in their tendency to exhibit last-male precedence.
Competition of sperm from two tester male genotypes (bwD and B3-09, a third
chromosome isogenic line from Beltsville, MD) was quantified by doubly mating
female lines that had been rendered homozygous for X, second, or third
chromosomes isolated from natural populations. The composite sperm displacement
parameter, P2', was highly heterogeneous among lines, whether or not viability
effects were compensated, implying the presence of polymorphic genes affecting
access of sperm to eggs. Genetic variation of this type is completely neutral in
the absence of pleiotropy or interaction between variation in the two sexes.
PMID- 9649537
TI - Isolation of the gene encoding the Drosophila melanogaster homolog of the
Saccharomyces cerevisiae GCN2 eIF-2alpha kinase.
AB - Genomic and cDNA clones homologous to the yeast GCN2 eIF-2alpha kinase (yGCN2)
were isolated from Drosophila melanogaster. The identity of the Drosophila GCN2
(dGCN2) gene is supported by the unique combination of sequence encoding a
protein kinase catalytic domain and a domain homologous to histidyl-tRNA
synthetase and by the ability of dGCN2 to complement a deletion mutant of the
yeast GCN2 gene. Complementation of Deltagcn2 in yeast by dGCN2 depends on the
presence of the critical regulatory phosphorylation site (serine 51) of eIF
2alpha. dGCN2 is composed of 10 exons encoding a protein of 1589 amino acids.
dGCN2 mRNA is expressed throughout Drosophila development and is particularly
abundant at the earliest stages of embryogenesis. The dGCN2 gene was
cytogenetically and physically mapped to the right arm of the third chromosome at
100C3 in STS Dm2514. The discovery of GCN2 in higher eukaryotes is somewhat
unexpected given the marked differences between the amino acid biosynthetic
pathways of yeast vs. Drosophila and other higher eukaryotes. Despite these
differences, the presence of GCN2 in Drosophila suggests at least partial
conservation from yeast to multicellular organisms of the mechanisms responding
to amino acid deprivation.
PMID- 9649538
TI - Nonneutral evolution and differential mutation rate of gender-associated
mitochondrial DNA lineages in the marine mussel Mytilus.
AB - Mussels have two types of mitochondrial DNA (mtDNA). The M type is transmitted
paternally, and the F type is transmitted maternally. To test hypotheses of the
molecular evolution of both mtDNA genomes, 50 nucleotide sequences were obtained
for 396 bp of the COIII gene of European populations of Mytilus edulis and the
Atlantic and Mediterranean forms of M. galloprovincialis. Analysis based on the
proportion of synonymous and nonsynonymous substitutions indicate that mtDNA is
evolving in a non-neutral and complex fashion. Previous studies on American
mussels demonstrated that the F genome experiences a higher purifying selection
and that the M genome evolves faster. Here we show that these patterns also hold
in European populations. However, in contrast to American populations, where an
excess of replacement substitution between F and M lineages has been reported, a
significant excess of replacement polymorphism within mtDNA lineages is observed
in European populations of M. galloprovincialis. European populations also show
an excess of replacement polymorphism within the F but not within the M genome
with respect to American M. trossulus, as well as a consistent pattern of excess
of rare variants in both F and M genomes. These results are consistent with a
nearly neutral model of molecular evolution and a recent relaxation of selective
constraints on European mtDNA. Levels of diversity are significantly higher for
the M than F genome, and the M genome also accumulates synonymous and
nonsynonymous substitutions at a higher rate, in contrast with earlier reports
where no difference for the synonymous rate was observed. It is suggested that a
subtle balance between relaxed selection and a higher mutation rate explains the
faster evolutionary rate of the M lineage.
PMID- 9649539
TI - Linkage relationships and haplotype polymorphism among cichlid Mhc class II B
loci.
AB - The species flocks of cichlid fishes in the Great East African Lakes are
paradigms of adaptive radiation and hence, of great interest to evolutionary
biologists. Phylogenetic studies of these fishes have, however, been hampered by
the lack of suitable polymorphic markers. The genes of the major
histocompatibility complex hold the promise to provide, through their extensive
polymorphism, a large number of such markers, but their use has been hampered by
the complexity of the genetic system and the lack of definition of the individual
loci. In this study we take the first substantial step to alleviate this problem.
Using a combination of methods, including the typing of single sperm cells, gyno-
or androgenetic individuals, and haploid embryos, as well as sequencing of class
II B restriction fragments isolated from gels for Southern blots, we identify the
previously characterized homology groups as distinct loci. At least 17
polymorphic class II B loci, all of which are presumably transcribed, have been
found among the different species studied. Most of these loci are shared across
the various cichlid species and genera. The number of loci per haplotype varies
from individual to individual, ranging from 1 to 13. A total of 21 distinct
haplotypes differing in the number of loci they carry has thus far been
identified. All the polymorphic loci are part of the same cluster in which,
however, distances between at least some of the loci (as indicated by
recombination frequencies) are relatively large. Both the individual loci and the
haplotypes can now be used to study phylogenetic relationships among the members
of the species flocks and the mode in which speciation occurs during adaptive
radiation.
PMID- 9649540
TI - Inference of population history using a likelihood approach.
AB - We introduce an approach to revealing the likelihood of different population
histories that utilizes an explicit model of sequence evolution for the DNA
segment under study. Based on a phylogenetic tree reconstruction method we show
that a Tamura-Nei model with heterogeneous mutation rates is a fair description
of the evolutionary process of the hypervariable region I of the mitochondrial
DNA from humans. Assuming this complex model still allows the estimation of
population history parameters, we suggest a likelihood approach to conducting
statistical inference within a class of expansion models. More precisely, the
likelihood of the data is based on the mean pairwise differences between DNA
sequences and the number of variable sites in a sample. The use of likelihood
ratios enables comparison of different hypotheses about population history, such
as constant population size during the past or an increase or decrease of
population size starting at some point back in time. This method was applied to
show that the population of the Basques has expanded, whereas that of the Biaka
pygmies is most likely decreasing. The Nuu-Chah-Nulth data are consistent with a
model of constant population.
PMID- 9649541
TI - A rank-based nonparametric method for mapping quantitative trait loci in outbred
half-sib pedigrees: application to milk production in a granddaughter design.
AB - We describe the development of a multipoint nonparametric quantitative trait loci
mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib
pedigrees. The method has been evaluated on a simulated dataset and its
efficiency compared with interval mapping by using regression. It was shown that
the rank-based approach is slightly inferior to regression when the residual
variance is homoscedastic normal; however, in three out of four other scenarios
envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed,
and homoscedastic positively kurtosed, the latter outperforms the former one.
Both methods were applied to a real data set analyzing the effect of bovine
chromosome 6 on milk yield and composition by using a 125-cM map comprising 15
microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires.
PMID- 9649542
TI - Quantitative trait locus mapping in dairy cattle by means of selective milk DNA
pooling using dinucleotide microsatellite markers: analysis of milk protein
percentage.
AB - "Selective DNA pooling" accomplishes quantitative trait locus (QTL) mapping
through densitometric estimates of marker allele frequencies in pooled DNA
samples of phenotypically extreme individuals. With poly(TG) microsatellites,
such estimates are confounded by "shadow" ("stutter") bands. A correction
procedure was developed on the basis of an observed linear regression between
shadow band intensity and allele TG repeat number. Using this procedure, a
selective DNA pooling study with respect to milk protein percentage was
implemented in Israel-Holstein dairy cattle. Pools were prepared from milk
samples of high and low daughters of each of seven sires and genotyped with
respect to 11 markers. Highly significant associations with milk protein
percentage were found for 5 of the markers; 4 of these markers confirmed previous
reports. Selective DNA pooling accessed 80.6 and 48.3%, respectively, of the
information that would have been available through individual selective
genotyping or total population genotyping. In effect, the statistical power of
45,600 individual genotypings was obtained from 328 pool genotypings. This
methodology can make genome-wide mapping of QTL accessible to moderately sized
breeding organizations.
PMID- 9649543
TI - Characterization of Soymar1, a mariner element in soybean.
AB - Mariner elements, a family of DNA-mediated transposable elements with short,
inverted terminal repeats, have been reported in a wide variety of arthropods, as
well as planarians, nematodes, and humans. No such element has been reported in a
plant. Here we report a mariner element in the plant soybean (Glycine max (L.)
Merr.). Although this sequence belongs to the mariner family, it is clearly
distinct from previously reported mariner-like elements, as well as from the Tc1
transposon family. Novel aspects of its sequence could be useful as a starting
point to identify mariner-like elements in new organisms, and it may prove useful
in creating a transformation vector for plants.
PMID- 9649544
TI - Characterization of an unstable allele of the Arabidopsis HY4 locus.
AB - The Arabidopsis HY4 gene encodes the nonessential blue light photoreceptor CRY1.
Loss-of-function hy4 mutants have an elongated hypocotyl phenotype after
germination under blue light. We previously analyzed 20 independent hy4 alleles
produced by fast neutron mutagenesis. These alleles were grouped into two classes
based on their genetic behavior and corresponding deletion size: (1) null hy4
alleles that were semidominant over wild type and contained small or moderate
sized deletions at HY4 and (2) null hy4 alleles that were recessive lethal and
contained large HY4 deletions. Here we describe one additional fast neutron hy4
mutant, B144, that did not fall into either of these two classes. Mutant B144 was
isolated as a heterozygote with an intermediate hy4 phenotype. One allele from
this mutant, hy4-B144(Delta), contains a large deletion at HY4 and is recessive
lethal. The other allele from this mutant, HY4-B144*, appears to be intact and
functional but is unstable and spontaneously converts to a nonfunctional hy4
allele. In addition, HY4-B144* is lethal in homozygotes and suppresses local
recombination. We discuss genetic and epigenetic mechanisms that may account for
the unusual behavior of the HY4-B144* allele.
PMID- 9649545
TI - Molecular characterization of S locus genes, SLG and SRK, in a pollen-recessive
self-incompatibility haplotype of Brassica rapa L.
AB - In Brassica species that exhibit self-incompatibility, two genes, SLG and SRK, at
the S locus are involved in the recognition reaction with self and non-self
pollen. From a pollen-recessive S29 haplotype of Brassica rapa, both cDNA and
genomic DNA clones for these two genes were isolated and characterized. The
nucleotide sequence for the S domain of SRK29 showed a high degree of similarity
with that of SLG29, and they belong to Class II type. RNA gel blot analysis
showed that the transcript of SLG29 consisted of the first and second exons, and
no other transcript containing any part of the intron sequence was detected.
Because no transmembrane domain was encoded by the second exon of SLG29, SLG29
was designated a secreted type glycoprotein. SLGs of two other pollen-recessive
haplotypes, S40 and S44, of B. rapa also had a similar structure to that of
SLG29. Previously, SLG2 from a pollen-recessive haplotype, S2, of Brassica
oleracea was found to produce two different transcripts, one for the secreted
type glycoprotein and the other for a putative membrane-anchored form of SLG.
Therefore, the nature of these SLGs from pollen-recessive haplotypes of B. rapa
is different from that of SLG2 of B. oleracea.
PMID- 9649546
TI - The expected number of heterozygous sites in a subdivided population.
AB - A simple, exact formula is derived for the expected number of heterozygous sites
per individual at equilibrium in a subdivided population. The model of infinitely
many neutral sites is posited; the linkage map is arbitrary. The monoecious,
diploid population is subdivided into a finite number of panmictic colonies that
exchange gametes. The backward migration matrix is arbitrary, but time
independent and ergodic (i.e., irreducible and aperiodic). With suitable
weighting, the expected number of heterozygous sites is 4Neu, where Ne denotes
the migration effective population number and u designates the total mutation
rate per gene (or DNA sequence). For diploid migration, this formula is a good
approximation if Ne >> 1.
PMID- 9649547
TI - On the sampling variance of intraclass correlations and genetic correlations.
AB - Widely used standard expressions for the sampling variance of intraclass
correlations and genetic correlation coefficients were reviewed for small and
large sample sizes. For the sampling variance of the intraclass correlation, it
was shown by simulation that the commonly used expression, derived using a first
order Taylor series performs better than alternative expressions found in the
literature, when the between-sire degrees of freedom were small. The expressions
for the sampling variance of the genetic correlation are significantly biased for
small sample sizes, in particular when the population values, or their estimates,
are close to zero. It was shown, both analytically and by simulation, that this
is because the estimate of the sampling variance becomes very large in these
cases due to very small values of the denominator of the expressions. It was
concluded, therefore, that for small samples, estimates of the heritabilities and
genetic correlations should not be used in the expressions for the sampling
variance of the genetic correlation. It was shown analytically that in cases
where the population values of the heritabilities are known, using the estimated
heritabilities rather than their true values to estimate the genetic correlation
results in a lower sampling variance for the genetic correlation. Therefore, for
large samples, estimates of heritabilities, and not their true values, should be
used.
PMID- 9649548
TI - Correlation between the substitution rate and rate variation among sites in
protein evolution.
AB - It is well known that the rate of amino acid substitution varies among different
proteins and among different sites of a protein. It is, however, unclear whether
the extent of rate variation among sites of a protein and the mean substitution
rate of the protein are correlated. We used two approaches to analyze orthologous
protein sequences of 51 nuclear genes of vertebrates and 13 mitochondrial genes
of mammals. In the first approach, no assumptions of the distribution of the rate
variation among sites were made, and in the second approach, the gamma
distribution was assumed. Through both approaches, we found a negative
correlation between the extent of among-site rate variation and the average
substitution rate of a protein. That is, slowly evolving proteins tend to have a
high level of rate variation among sites, and vice versa. We found this
observation consistent with a simple model of the neutral theory where most sites
are either invariable or neutral. We conclude that the correlation is a general
feature of protein evolution and discuss its implications in statistical tests of
positive Darwinian selection and molecular time estimation of deep divergences.
PMID- 9649549
TI - Fallen arches, or how the vertebrate got its head.
PMID- 9649550
TI - AZT treatment induces molecular and ultrastructural oxidative damage to muscle
mitochondria. Prevention by antioxidant vitamins.
AB - AIDS patients who receive zidovudine (AZT) frequently suffer from myopathy. This
has been attributed to mitochondrial (mt) damage, and specifically to the loss of
mtDNA. This study examines whether AZT causes oxidative damage to DNA in patients
and to skeletal muscle mitochondria in mice, and whether this damage may be
prevented by supranutritional doses of antioxidant vitamins. Asymptomatic HIV
infected patients treated with AZT have a higher urinary excretion (355+/-100
pmol/kg/d) of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxo-dG) (a marker of
oxidative damage to DNA) than untreated controls (asymptomatic HIV-infected
patients) (182+/-29 pmol/kg/d). This was prevented (110+/-79 pmol/kg/d) by
simultaneous oral treatment with AZT plus antioxidant vitamins (C and E). Mice
treated with AZT also had a significantly higher urinary excretion of 8-oxo-dG
than controls. Skeletal muscle mtDNA of mice treated with AZT had more 8-oxo-dG
than controls. mt lipoperoxidation was also increased and skeletal muscle
glutathione was oxidized. These effects may be due to an increased peroxide
production by muscle mitochondria of AZT-treated animals. Dietary supplements
with vitamins C and E at supranutritional doses protect against oxidative damage
to skeletal muscle mitochondria caused by AZT.
PMID- 9649551
TI - Abnormalities of nasal potential difference measurement in Liddle's syndrome.
AB - In Liddle's syndrome, a rare inherited form of hypertension, epithelial sodium
channel mutations appear to cause high blood pressure by increasing sodium
reabsorption through sodium channels in the renal distal tubule. This increase in
channel activity has not been confirmed previously by in vivo measurement. We
have made transnasal potential difference measurements (effective in detection of
increased sodium channel activity in cystic fibrosis) in three brothers with
genetically proven Liddle's syndrome, their unaffected sister, and 40
normotensive controls. Maximum potential difference after 2 wk off treatment in
the affected brothers was -30.4+/-1.2 mV (values mean+/-SD, lumen-negative with
respect to submucosa) and was significantly more lumen-negative than that of the
control group (-18.6+/-6.8 mV, P = 0.0228) or the unaffected sister (-18.25 mV, P
< 0.01). The change in potential difference after topical application of 10(-)4 M
amiloride was greater in the Liddle's patients, 14.0+/-2.1 mV, than in controls
(7.9+/-3.9 mV, P = 0.0126) or the unaffected sister (5.5 mV, P < 0.05). This is
the first in vivo demonstration of increased sodium channel activity in Liddle's
syndrome. If these results are confirmed in other kindreds with this condition,
then nasal potential difference measurements could provide a simple clinical test
for Liddle's syndrome.
PMID- 9649552
TI - The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis
transmembrane conductance regulator in normal but not in cystic fibrosis airways.
AB - Cystic fibrosis (CF) airway cells, besides their well-known defect in cAMP
dependent Cl- conductance, are characterized by an enhanced Na+ conductance. In
this study we have examined the Na+ conductance in human respiratory tract by
measuring transepithelial voltage and resistance (Vte, Rte) and by assessing
membrane voltages (Vm) of freshly isolated airway epithelial cells from CF and
non-CF patients. Basal amiloride inhibitable (10 micromol/liter) equivalent short
circuit current (Isc = Vte/Rte) was significantly increased in CF compared with
non-CF tissues. After stimulation by forskolin (10 micromol/liter) a significant
depolarization of Vm corresponding to the cAMP-dependent activation of a Cl-
conductance was observed in non-CF but not in CF airway cells. In non-CF tissue
but not in CF tissue the effects of amiloride and N-methyl-D-glucamine on Vm were
attenuated in the presence of forskolin. Also the amiloride-inhibitable Isc was
significantly reduced by forskolin (1 micromol/liter) and isobutylmethylxanthine
(IBMX; 100 micromol/liter) only in non-CF tissue. We conclude that cystic
fibrosis transmembrane conductance regulator acts as a downregulator of
epithelial Na+ channels in human airways. This downregulation of epithelial Na+
channels is absent in CF airways, leading to hyperabsorption and to the
characteristic increase in mucus viscosity.
PMID- 9649553
TI - Role of Endothelin-1/Endothelin-A receptor-mediated signaling pathway in the
aortic arch patterning in mice.
AB - The intercellular signaling mediated by endothelins and their G protein-coupled
receptors has recently been shown to be essential for the normal embryonic
development of subsets of neural crest cell derivatives. Endothelin-1 (ET-1) is
proteolytically generated from its inactive precursor by endothelin-converting
enzyme-1 (ECE-1) and acts on the endothelin-A (ETA) receptor. Genetic disruption
of this ET-1/ECE-1/ETA pathway results in defects in branchial arch- derived
craniofacial tissues, as well as defects in cardiac outflow and great vessel
structures, which are derived from cephalic (cardiac) neural crest. In this
study, in situ hybridization of ETA-/- and ECE-1(-)/- embryos with a cardiac
neural crest marker, cellular retinoic acid-binding protein-1, shows that the
migration of neural crest cells from the neural tube to cardiac outflow tract is
not affected in these embryos. Immunostaining of an endothelial marker, platelet
endothelial cell adhesion molecule CD-31, shows that the initial formation of the
branchial arch arteries is not disturbed in ETA-/- or ECE-1(-)/- embryos. To
visualize the subsequent patterning of arch vessels in detail, we generated ETA-/
or ECE-1(-)/- embryos that expressed an SM22alpha-lacZ marker transgene in
arterial smooth muscle cells. Wholemount X-gal staining of these mutant embryos
reveals that the abnormal regression and persistence of specific arch arteries
results in disturbance of asymmetrical remodeling of the arch arteries. These
defects include abnormal regression of arch arteries 4 and 6, enlargement of arch
artery 3, and abnormal persistence of the bilateral ductus caroticus and right
dorsal aorta. These abnormalities eventually lead to various types of great
vessel malformations highly similar to those seen in neural crest-ablated chick
embryos and human congenital cardiac defects. This study demonstrates that ET
1/ETA-mediated signaling plays an essential role in a complex process of aortic
arch patterning by affecting the postmigratory cardiac neural crest cell
development.
PMID- 9649554
TI - Absence of functional receptors for parathyroid hormone and parathyroid hormone
related peptide in Blomstrand chondrodysplasia.
AB - We report the absence of functional parathyroid hormone (PTH)/PTH-related peptide
(PTHrP) receptors (PTH/PTHrP receptor) in Blomstrand chondrodysplasia, a genetic
disorder characterized by advanced endochondral bone maturation. Analysis of
PTH/PTHrP receptor genomic DNA from a patient with Blomstrand chondrodysplasia
demonstrated that the patient was heterozygous for a point mutation (G--> A
substitution at nucleotide 1176) inherited from the mother. Analysis of PTH/PTHrP
receptor cDNA demonstrated that: (a) this point mutation caused the deletion of
the first 11 amino acids of exon M5 (encoding the fifth transmembrane domain of
the receptor), resulting from the use of a novel splice site created by the base
substitution; (b) the mutant receptor was well expressed in COS-7 cells, but did
not bind PTH or PTHrP, and failed to induce detectable stimulation of either cAMP
or inositol phosphate production in response to these ligands; and (c) the
paternal allele was not expressed. Thus, only the abnormal and nonfunctional
PTH/PTHrP receptors encoded by the maternal allele were expressed by chondrocytes
from this patient. In view of the known role played by the PTH/PTHrP receptor in
bone and cartilage development, these results strongly support the conclusion
that the absence of functional PTH/ PTHrP receptors is responsible for the
skeletal abnormalities seen in Blomstrand chondrodysplasia, abnormalities that
are the mirror image of those observed in Jansen's chondrodysplasia. These
findings emphasize the importance of signaling through this receptor in human
fetal skeletal development.
PMID- 9649555
TI - Exacerbation of antigen-induced arthritis in urokinase-deficient mice.
AB - In rheumatoid arthritis, synovial expression of urokinase (uPA) activity is
greatly increased (Busso, N., V. Peclat, A. So, and A. -P. Sappino. 1997. Ann.
Rheum. Dis. 56:550- 557). We report the same effect in murine antigen-induced
arthritis. uPA-mediated plasminogen activation in arthritic joints may have
deleterious effects via degradation of cartilage and bone matrix proteins as well
as beneficial effects via fibrin degradation. We evaluated these contrasting
effects in vivo by analyzing the phenotype of uPA-deficient (uPA-/-) and control
mice during antigen-induced arthritis. Joint inflammation was comparable in both
groups up to day 3 and subsequently declined in control mice, remaining
significantly elevated in uPA-/- mice on days 10 and 30 after arthritis onset.
Likewise, synovial thickness was markedly increased in uPA-deficient mice
persisting for up to 2 mo, whereas it subsided in control animals. Bone erosion
was exacerbated in uPA-/- mice on day 30. By contrast, no difference in articular
cartilage proteoglycan content was found between both groups. Significantly
increased accumulation of fibrin was observed by day 30 in arthritic joints of
uPA-/- mice. We hypothesized that synovial fibrin deposition plays a role in
joint inflammation. Accordingly, defibrinogenation of uPA-/- mice by ancrod
significantly decreased the sustained joint inflammation. All the above
observations were reproducible in plasminogen-deficient (Pln-/-) mice. In
conclusion, synovial fibrin deposition plays a role as a nonimmunological
mechanism which sustains chronic arthritis.
PMID- 9649556
TI - Induction of B cell responses in the stomach of Helicobacter pylori- infected
subjects after oral cholera vaccination.
AB - We have evaluated the possibility of inducing antibody responses locally in the
human stomach as a prerequisite for the development of a vaccine against
Helicobacter pylori. Both H. pylori-infected and noninfected subjects were
immunized with an oral B subunit whole cell (BS-WC) cholera vaccine, and total
and vaccine-specific antibody-secreting cells (ASC) were determined by the enzyme
linked immunospot (ELISPOT) technique in cells isolated from the antrum and
duodenum, respectively, before and after vaccination. Most of the subjects
responded to the vaccination with high frequencies of vaccine-specific ASCs in
the duodenum as well as high-serum antibody titers, and no significant
differences were seen in the responses between H. pylori- infected and
noninfected subjects. When studying the gastric mucosa, on the other hand, there
were dramatic differences between the H. pylori-infected and the noninfected
subjects. Thus, whereas none of the noninfected subjects responded to the
immunization in antrum, most of the H. pylori-infected subjects had high
frequencies of vaccine-specific ASCs in this location after vaccination.
Furthermore, the H. pylori-infected subjects had strikingly higher (as a mean 80
fold) frequencies of total IgA-secreting cells in antrum than the noninfected
subjects, whereas the frequencies of total IgA-secreting cells in the duodenum
were comparable between the groups. In conclusion, these results demonstrate the
possibility of inducing antibody responses locally in the gastric mucosa of H.
pylori-infected individuals, a finding with obvious implications for the future
development of a therapeutic vaccine against H. pylori.
PMID- 9649557
TI - An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic
diabetes insipidus is retained in the Golgi complex.
AB - Mutations in the aquaporin-2 (AQP2) water channel gene cause autosomal recessive
nephrogenic diabetes insipidus (NDI). Here we report the first patient with an
autosomal dominant form of NDI, which is caused by a G866A transition in the AQP2
gene of one allele, resulting in a E258K substitution in the C-tail of AQP2. To
define the molecular cause of NDI in this patient, AQP2-E258K was studied in
Xenopus oocytes. In contrast to wild-type AQP2, AQP2-E258K conferred a small
increase in water permeability, caused by a reduced expression at the plasma
membrane. Coexpression of wild-type AQP2 with AQP2-E258K, but not with an AQP2
mutant in recessive NDI (AQP2-R187C), revealed a dominant-negative effect on the
water permeability conferred by wild-type AQP2. The physiologically important
phosphorylation of S256 by protein kinase A was not affected by the E258K
mutation. Immunoblot and microscopic analyses revealed that AQP2-E258K was, in
contrast to AQP2 mutants in recessive NDI, not retarded in the endoplasmic
reticulum, but retained in the Golgi compartment. Since AQPs are thought to
tetramerize, the retention of AQP2-E258K together with wild-type AQP2 in mixed
tetramers in the Golgi compartment is a likely explanation for the dominant
inheritance of NDI in this patient.
PMID- 9649558
TI - Dietary supplement with vitamin C prevents nitrate tolerance.
AB - Enhanced formation of superoxide radicals has been proposed to play a major role
in the development of nitrate tolerance in humans. We tested the effects of
vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic
effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h)
in nine healthy subjects. Tolerance development was monitored by changes in
arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with
GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three
different series in the same subjects. GTN treatment caused an immediate rise in
arterial conductivity (a/b ratio of dicrotic pulse), but within 2 d of initiating
GTN, the a/b ratio progressively decreased and reached basal levels. In addition,
there was a progressive loss of the orthostatic decrease in blood pressure.
However, coadministration of Vit-C and GTN fully maintained the GTN-induced
changes in the orthostatic blood pressure, and the rise of a/b ratio was
augmented by 310% for the duration of the test period. Changes in vascular
tolerance in GTN-treated subjects were paralleled by upregulation of the activity
of isolated platelets, which was also reversed by Vit-C administration. These
findings demonstrate that dietary supplementation with Vit-C eliminates vascular
tolerance and concomitant upregulation of ex vivo-washed platelet activity during
long-term nonintermittent administration of GTN in humans.
PMID- 9649559
TI - In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases
cardiomyocyte calcium responsiveness and contractility in transgenic mouse
hearts.
AB - Recently, it has been reported that the protein kinase C (PKC) beta isoform plays
a critical role in the development of hypertrophy and heart failure. The purpose
of the present study was to clarify the mechanism by which activation of PKCbeta
led to depressed cardiac function. Thus, we used a PKCbeta2 overexpressing mouse,
an animal model of heart failure, to examine mechanical properties and Ca2+
signals of isolated left ventricular cardiomyocytes. The percentage of
shortening, rate of shortening, and rate of relengthening of cardiomyocytes were
markedly reduced in PKCbeta2 overexpression mice compared to wild-type control
mice, although the baseline level and amplitude of Ca2+ signals were similar.
These findings suggested a decreased myofilament responsiveness to Ca2+ in
transgenic hearts. Therefore, the incorporation of [32P] inorganic phosphate into
cardiac myofibrillar proteins was studied in Langendorff-perfused hearts. There
was a significant increase in the degree of phosphorylation of troponin I in
PKCbeta2-overexpressing transgenic mice. The depressed cardiomyocyte function
improved after the superfusion of a PKCbeta selective inhibitor. These findings
indicate that in vivo PKCbeta2-mediated phosphorylation of troponin I may
decrease myofilament Ca2+ responsiveness, and thus causes cardiomyocyte
dysfunction. Since chronic and excess activation of PKCbeta2 plays a direct and
contributory role in the progression of cardiac dysfunction, the PKCbeta
selective inhibitor may provide a new therapeutic modality in the setting of
heart failure.
PMID- 9649560
TI - In vivo analysis of Fas/FasL interactions in HIV-infected patients.
AB - Recent insights into the pharmacological control of HIV replication and the
molecular mechanisms of peripheral T cells homeostasis allowed us to investigate
in vivo the mechanisms mediating T cell depletion in HIV-infected patients.
Before the initiation of highly active antiretroviral therapy (HAART), a high
degree of lymphoid tissue apoptosis is present, which is reduced upon HAART
initiation (P < 0.001) and directly correlates with reduction of viral load and
increases of peripheral T lymphocytes (P < 0.01). Because Fas/FasL interactions
play a key role in peripheral T lymphocyte homeostasis, we investigated the
susceptibility to Fas-mediated apoptosis in peripheral T lymphocytes and of FasL
expression in lymphoid tissue before and during HAART. High levels of Fas
susceptibility found in peripheral CD4 T lymphocytes before HAART were
significantly reduced after HAART, coinciding with decreases in viral load (P =
0.018) and increases in peripheral CD4 T lymphocyte counts (P < 0.01). However,
the increased FasL expression in the lymphoid tissue of HIV-infected individuals
was not reduced after HAART. These results demonstrate that lymphoid tissue
apoptosis directly correlates with viral load and peripheral T lymphocyte
numbers, and suggest that HIV-induced susceptibility to Fas-dependent apoptosis
may play a key role in the regulation of T cell homeostasis in HIV-infected
individuals.
PMID- 9649561
TI - Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40
large T antigen to the osteoclast lineage in transgenic mice.
AB - Cellular and molecular characterization of osteoclasts (OCL) has been extremely
difficult since OCL are rare cells, and are difficult to isolate in large
numbers. We used the tartrate-resistant acid phosphatase promoter to target the
bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL
lineage in transgenic mice as a means of immortalizing OCL precursors.
Immunocytochemical studies confirmed that we had targeted Bcl-XL and/or Tag to
OCL, and transformed and mitotic OCL were readily apparent in bones from both Tag
and bcl-XL/Tag mice. OCL formation in primary bone marrow cultures from bcl-XL,
Tag, or bcl-XL/Tag mice was twofold greater compared with that of nontransgenic
littermates. Bone marrow cells from bcl-XL/Tag mice, but not from singly
transgenic bcl-XL or Tag mice, have survived in continuous culture for more than
a year. These cells form high numbers of bone-resorbing OCL when cultured using
standard conditions for inducing OCL formation, with approximately 50% of the
mononuclear cells incorporated into OCL. The OCL that form express calcitonin
receptors and contract in response to calcitonin. Studies examining the
proliferative capacity and the resistance of OCL precursors from these transgenic
mice to apoptosis demonstrated that the increased numbers of OCL precursors in
marrow from bcl-XL/Tag mice was due to their increased survival rather than an
increased proliferative capacity compared with Tag, bcl-XL, or normal mice.
Histomorphometric studies of bones from bcl-XL/Tag mice also confirmed that there
were increased numbers of OCL precursors (TRAP + mononuclear cells) present in
vivo. These data demonstrate that by targeting both bcl-XL and Tag to cells in
the OCL lineage, we have immortalized OCL precursors that form bone-resorbing OCL
with an efficiency that is 300-500 times greater than that of normal marrow.
PMID- 9649562
TI - Role of interleukin 10 in specific immunotherapy.
AB - The induction of allergen-specific anergy in peripheral T cells represents a key
step in specific immunotherapy (SIT). Here we demonstrate that the anergic state
results from increased IL-10 production. In bee venom (BV)-SIT the specific
proliferative and cytokine responses against the main allergen, the phospholipase
A2 (PLA), and T cell epitope-containing PLA peptides were significantly
suppressed after 7 d of treatment. Simultaneously, the production of IL-10
increased during BV-SIT. After 28 d of BV-SIT the anergic state was established.
Intracytoplasmic cytokine staining of PBMC combined with surface marker detection
revealed that IL-10 was produced initially by activated CD4(+)CD25(+), allergen
specific T cells, and followed by B cells and monocytes. Neutralization of IL-10
in PBMC fully reconstituted the specific proliferative and cytokine responses. A
similar state of IL-10-associated T cell anergy, as induced in BV-SIT, was found
in hyperimmune individuals who recently had received multiple bee stings. The
addition of IL-10 to soluble CD40 ligand IL-4-stimulated PBMC or purified B cells
inhibited the PLA-specific and total IgE and enhanced the IgG4 formation.
Accordingly, increased IL-10 production by SIT causes specific anergy in
peripheral T cells, and regulates specific IgE and IgG4 production toward normal
IgG4-related immunity.
PMID- 9649563
TI - Molecular defects in ferrochelatase in patients with protoporphyria requiring
liver transplantation.
AB - Protoporphyria is a genetic disorder in which a deficiency of mitochondrial
ferrochelatase activity causes accumulation of protoporphyrin that produces
severe liver damage in some patients. In this study, mutations of the
ferrochelatase gene were examined in eight unrelated patients who had liver
transplantation. RNA was prepared from liver and/ or lymphoblasts, and specific
reverse transcriptase-nested polymerase chain reactions amplified and sequenced
ferrochelatase cDNAs. Products shorter than normal resulted from an exon 3
deletion in three patients, exon 10 deletion in two, exon 2 deletion in one, and
deletion of five nucleotides in exon 5 in one. Sequence of normal-size products
revealed no other mutations. Western blot showed a reduced quantity of normal
size ferrochelatase protein in protoporphyria liver compared with normal liver
(19-51%, mean 32% of normal). Levels of the mitochondrial protein F1-ATPase beta
subunit were not decreased to a similar degree. Liver ferrochelatase activity was
reduced more than could be explained by the decrease in ferrochelatase protein (4
20%, mean 9% of normal). These results establish genetic heterogeneity in the
most severe phenotype of protoporphyria. However, the gene mutations found share
the property of causing a major structural alteration in the ferrochelatase
protein.
PMID- 9649564
TI - Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host
disease after allogeneic bone marrow transplantation.
AB - Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a
murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H
antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, IL-11
administration polarized the donor T cell cytokine responses to host antigen
after BMT with a 50% reduction in IFNgamma and IL-2 secretion and a 10-fold
increase in IL-4. This polarization of T cell responses was associated with
reduced IFNgamma serum levels and decreased IL-12 production in mixed lymphocyte
cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum
endotoxin levels by 80%. Treatment with IL-11 also reduced TNFalpha serum levels
and suppressed TNFalpha secretion by macrophages to LPS stimulation in vitro. IL
11 thus decreased GVHD morbidity and mortality by three mechanisms: (a)
polarization of donor T cells; (b) protection of the small bowel; and (c)
suppression of inflammatory cytokines such as TNFalpha. We conclude that brief
treatment with IL-11 may represent a novel strategy to prevent T cell-mediated
inflammatory processes such as GVHD.
PMID- 9649565
TI - Absence of polycythemia in a child with a unique erythropoietin receptor mutation
in a family with autosomal dominant primary polycythemia.
AB - Primary familial and congenital polycythemia (PFCP or familial erythrocytosis) is
a rare proliferative disorder of erythroid progenitor cells, characterized by
elevated erythrocyte mass and hemoglobin concentration, hypersensitivity of
erythroid progenitors to erythropoietin (EPO), and autosomal dominant inheritance
or sporadic occurrence. A number of EPO receptor (EPOR) mutations were found in
subjects with PFCP; most of these mutations resulted in the truncation of the
COOH-terminal of the EPOR protein. We studied a family with autosomal dominant
inheritance of PFCP in which four subjects were affected in three generations. We
screened the affected individuals for EPOR gene mutations using SSCP analysis and
found a C5964G mutation in exon VIII that changes tyrosine codon 426 to a
translation termination codon resulting in an EPOR protein truncated by 83 amino
acids. The mutant C5964G-EPOR exhibited hypersensitive EPO-dependent
proliferation compared to the wild-type EPOR when tested in a murine interleukin
3-dependent myeloid cell line (FDC-P1). We also examined the segregation of the
mutation with PFCP in the family and found that a child in the third generation
inherited the mutation without having laboratory evidence of polycythemia.
Further in vitro analysis of the erythroid progenitor cells of this affected
child revealed that the progenitor cells were hypersensitive to EPO (a hallmark
of PFCP) suggesting the presence of the disease at the level of progenitor cells.
Failure of this child to develop polycythemia suggests the existence of as yet
unidentified environmental or genetic factors that may suppress disease
development.
PMID- 9649566
TI - Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting
from gene replacement of mouse Apoe with human Apoe*2.
AB - To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we
generated mice with a human APOE*2 allele in place of the mouse Apoe gene via
targeted gene replacement in embryonic stem cells. Mice expressing human apoE2
(2/2) have virtually all the characteristics of type III hyperlipoproteinemia.
Their plasma cholesterol and triglyceride levels are both twice to three times
those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an
identical manner. The 2/2 mice are markedly defective in clearing beta-migrating
VLDL particles, and spontaneously develop atherosclerotic plaques, even on a
regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates
development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons
between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid
difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP
and spontaneous atherosclerosis in mice.
PMID- 9649567
TI - Modulation of monocyte-endothelial cell interactions by platelet microparticles.
AB - Platelets, activated by various agonists, produce microparticles (MP) from the
plasma membrane, which are released into the extracellular space. Although the
mechanism of MP formation has been clarified, their biological importance remains
ill defined. We have recently shown that platelet-derived MP influence platelet
and endothelial cell function. In this study, we have further examined the
mechanism of cellular activation by platelet MP. To address the possibility that
they may influence monocyte-endothelial interactions, we used an in vitro assay
to examine their effects on the adhesion of monocytes to human umbilical vein
endothelial cells (HUVEC). Platelet MP increased the adhesion of monocytes to
HUVEC in a time- and dose-dependent manner. Maximal adhesion of monocytes to
resting HUVEC was observed after 24 h of stimulation with MP. Similar kinetics
were observed with U-937 (human promonocytic leukemia) cells, used as a model for
the blood-borne monocyte. Maximal adhesion of resting monocytes to MP-stimulated
HUVEC was observed after 5 h of stimulation with MP. The EC50s for MP-induced
increases in HUVEC, monocyte, and U-937 cell adhesion is 8.74, 43.41, and 10.83
microg/ml of MP protein, respectively. The induction of monocyte-endothelial
adhesion was mimicked by arachidonic acid isolated from MP. The observed
increased cellular adhesiveness correlated with MP-induced upregulation of cell
adhesion molecules. MP-stimulated HUVEC increased intracellular cell adhesion
molecule-1 (ICAM-1) but not vascular cell adhesion molecule-1 (VCAM-1), P-, or E
selectin expression. Monocyte and U-937 lymphocyte function-associated antigen-1
(CD11a/CD18) and macrophage antigen-1 (CD11b/ CD18, alpham/beta2) were both
upregulated upon MP stimulation, but an increase in p150,95 (CD11c/CD18), very
late antigen-1, or ICAM-1 expression was not observed. The functional importance
of these changes was demonstrated with blocking antibodies. MP also induced the
chemotaxis of U-937 cells in a dose-dependent manner with an EC50 of 4.40
microg/ml of MP protein. Similarly, arachidonic acid isolated from MP mimicked
the chemotactic response. A role for PKC was implicated in both adhesion and
chemotaxis. GF 109203X, a specific inhibitor of PKC, significantly reduced
monocyte-endothelial adhesion, as well as U-937 chemotaxis. The demonstration
that platelet MP may modulate important aspects of endothelial and monocyte
function provides a novel mechanism by which platelets may interact with such
cells in human atherosclerosis and inflammation.
PMID- 9649568
TI - The combined role of P- and E-selectins in atherosclerosis.
AB - P- and E-selectins are adhesion molecules mediating the first step in leukocyte
extravasation. Because their function in leukocyte adhesion is overlapping, we
hypothesized that there might be a combined effect of these selectins on the
development of atherosclerotic lesions. We bred P- and E-selectin-double
deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient
background (LDLR-/- P/E-/-) and compared lesion development in these mice to that
in mice wild type for both selectins (LDLR-/- P/E+/+). After 8 wk on atherogenic
diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that
were five times smaller than those in LDLR-/- P/E+/+ mice. The density of
macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/
P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta
but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the
lesions progressed to the fibrous plaque stage in both genotypes. However, the
lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less
calcified than those of LDLR-/- P/E +/+ mice. Our results suggest that P- and E
selectins together play an important role in both early and advanced stages of
atherosclerotic lesion development.
PMID- 9649569
TI - Regulatory mechanisms of growth hormone secretion are sexually dimorphic.
AB - Sexually dimorphic growth hormone (GH) secretory pattern is important in the
determination of gender-specific patterns of growth and metabolism in rats.
Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine
mechanisms governing this potential difference are not fully established. We have
compared pulsatile GH secretion profiles in young men and women in the baseline
state and during a continuous intravenous infusion of recombinant human insulin
like growth factor I (rhIGF-I). During the baseline study, men had large
nocturnal GH pulses and relatively small pulses during the rest of the day. In
contrast, women had more continuous GH secretion and more frequent GH pulses that
were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently
suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced
GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH
secretion and did not suppress the GH response to GHRH. These data demonstrate
the existence of sexual dimorphism in the regulatory mechanisms involved in GH
secretion in humans. The persistence of GH responses to GHRH in women suggests
that negative feedback by IGF-I might be expressed, in part, through suppression
of hypothalamic GHRH.
PMID- 9649570
TI - Integrin-dependent homotypic adhesion of neutrophils. Arachidonic acid activates
Raf-1/Mek/Erk via a 5-lipoxygenase- dependent pathway.
AB - AA stimulates integrin-dependent neutrophil adhesion, a critical early step in
acute inflammation. However, neither the signaling pathway(s) of AA-stimulated
adhesion, nor whether AA acts directly or through the generation of active
metabolites, has been elucidated. Previously, we have observed a tight
association between neutrophil Erk activation and homotypic adhesion in response
to chemoattractants acting through G protein-linked receptors. We now report a
similar association between homotypic adhesion and Erk activation in response to
AA. Erk activation was cyclooxygenase independent and required AA metabolism to
5(S)- hydroperoxyeicosatetraenoic acid (5-HpETE) via 5-lipoxygenase, but not the
further lipoxygenase-dependent metabolism of 5-HpETE to leukotrienes. AA
stimulation of Erk was accompanied by Raf-1 activation and was sensitive to
inhibitors of Raf-1 and Mek. Whereas activation of Erk by AA was pertussis toxin
sensitive, [3H]-AA binding to neutrophils was not saturable, suggesting that an
AA metabolite activates a G protein. Consistent with this hypothesis, Erk
activation by 5(S)-hydroxyeicosatetraenoic acid (5-HETE; lipoxygenase-independent
metabolite of 5-HpETE) was also pertussis toxin sensitive. These data suggest
that a 5-lipoxygenase metabolite of AA, e.g., 5-HETE, is released from AA-treated
cells to engage a plasma membrane-associated, pertussis toxin-sensitive, G
protein-linked receptor, leading to activation of Erk and adhesion via the Raf
1/Mek signal transduction pathway.
PMID- 9649571
TI - Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary
artery endothelium.
AB - Prostacyclin (PGI2) is a key mediator of pulmonary vasodilation in the perinatal
period and its synthesis in the pulmonary vasculature increases markedly during
late gestation due to enhanced expression of the rate-limiting enzyme
cyclooxygenase-1 (COX-1). The hormone estrogen may play a role in COX-1
upregulation since fetal estrogen levels rise dramatically during late gestation
and estrogen enhances PGI2 synthesis in nonpulmonary vascular cells. We therefore
studied the direct effects of estrogen on COX-1 expression in ovine fetal
pulmonary artery endothelial cells (PAEC). Exposure to estradiol-17beta (E2beta,
10(-)10 to 10(-)6 M) caused a dose-related increase in COX-1 mRNA expression that
was evident after 48 h and maximal at 10(-)8 M (fourfold increase). COX-1 mRNA
stability was unchanged, suggesting that the upregulation is mediated at the
level of transcription. E2beta treatment (10(-)8 M for 48 h) also caused a
threefold increase in COX-1 protein expression and a threefold increase in PGI2
synthesis stimulated by bradykinin, the calcium ionophore A23187, or arachidonic
acid. The estrogen receptor (ER) antagonist ICI 182,780 fully reversed the
effects of the hormone on COX-1 protein expression and on arachidonic acid
stimulated PGI2 synthesis, and ER expression was evident in the PAEC by
immunoblot analysis. These findings indicate that physiologic levels of estrogen
cause upregulation of COX-1 expression and PGI2 synthesis in fetal PAEC via
activation of PAEC ER. This process may play a critical role in optimizing the
capacity for PGI2-mediated pulmonary vasodilation at birth, and it may also be
involved in estrogen responsiveness in other vascular beds.
PMID- 9649572
TI - Incorporation of adenovirus in calcium phosphate precipitates enhances gene
transfer to airway epithelia in vitro and in vivo.
AB - Adenovirus (Ad)-mediated gene transfer to airway epithelia is inefficient because
the apical membrane lacks the receptor activity to bind adenovirus fiber protein.
Calcium phosphate (CaPi) precipitates have been used to deliver plasmid DNA to
cultured cell lines. However, such precipitates are not effective in many primary
cultures or in vivo. Here we show that incorporating recombinant adenovirus into
a CaPi coprecipitate markedly enhances transgene expression in cells that are
resistant to adenovirus infection. Enhancement requires that the virus be
contained in the precipitate and viral proteins are required to increase
expression. Ad: CaPi coprecipitates increase gene transfer by increasing fiber
independent binding of virus to cells. With differentiated cystic fibrosis (CF)
airway epithelia in vitro, a 20-min application of Ad:CaPi coprecipitates that
encode CF transmembrane conductance regulator produced as much CF transmembrane
conductance regulator Cl- current as a 24-h application of adenovirus alone. We
found that Ad:CaPi coprecipitates also increased transgene expression in mouse
lung in vivo; importantly, expression was particularly prominent in airway
epithelia. These results suggest a new mechanism for gene transfer that may be
applicable to a number of different gene transfer applications and could be of
value in gene transfer to CF airway epithelia in vivo.
PMID- 9649573
TI - Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the
EP1 receptor.
AB - PGE2 exerts potent diuretic and natriuretic effects on the kidney. This action is
mediated in part by direct inhibition of collecting duct Na+ absorption via a
Ca++-coupled mechanism. These studies examine the role the Ca++-coupled PGE-E EP1
receptor plays in mediating these effects of PGE2 on Na+ transport. Rabbit EP1
receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays
demonstrated highest expression of EP1 mRNA in kidney, followed by stomach,
adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP1
mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused
rabbit cortical collecting duct, EP1 active PGE analogs were 10-1, 000-fold more
potent in raising intracellular Ca++ than EP2, EP3, or EP4-selective compounds.
Two different EP1 antagonists, AH6809 and SC19220, completely blocked the PGE2
stimulated intracellular calcium increase. AH6809 also completely blocked the
inhibitory effect of PGE2 on Na+ absorption in microperfused rabbit cortical
collecting ducts. These studies suggest that EP1 receptor activation mediates
PGE2-dependent inhibition of Na+ absorption in the collecting duct, thereby
contributing to its natriuretic effects.
PMID- 9649574
TI - Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury
after ischemic acute renal failure in rat.
AB - We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is
responsible for the induction of nephrogenic mesenchyme during embryonic kidney
development. Gene knock-out studies showed that OP-1 null mutant mice die of
renal failure within the first day of postnatal life. In the present study, we
evaluated the effect of recombinant human OP-1 for the treatment of acute renal
failure after 60 min bilateral renal artery occlusion in rats. Bioavailability
studies in normal rats indicate that approximately 1.4 microg OP-1/ml is
available in the circulation 1 min after intravenous administration of 250
microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of
the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney.
We show that OP-1 preserves kidney function, as determined by reduced blood urea
nitrogen and serum creatinine, and increased survival rate when administered 10
min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h
after reperfusion. Histochemical and molecular analyses demonstrate that OP-1:
(a) minimizes infarction and cell necrosis, and decreases the number of plugged
tubules; (b) suppresses inflammation by downregulating the expression of
intercellular adhesive molecule, and prevents the accumulation and activity of
neutrophils; (c) maintains the expression of the vascular smooth muscle cell
phenotype in pericellular capillaries; and (d) reduces programmed cell death
during the recovery. Collectively, these data suggest that OP-1 prevents the loss
of kidney function associated with ischemic injury and may provide a basis for
the treatment of acute renal failure.
PMID- 9649575
TI - Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P
autoantibodies in healthy adults.
AB - A subset of SLE patients has serologically detectable autoantibodies to the
ribosomal P proteins (anti-P). We reported the discovery of covert anti-P
antibodies and their masking IgG-inhibitory antibodies in the sera of healthy
adults. The aim of this study was to determine if these IgG-inhibitory antibodies
are anti-idiotypic antibodies (anti-Ids). IgG and IgG-depleted fractions of
plasma from two healthy adults were assayed for inhibition of anti-P F(ab')2
binding to the ribosomal P proteins in immunoblot. Anti-P antibody activity was
completely inhibited by plasma IgG, whereas there was no inhibition by IgG
depleted plasma. IgG-inhibitory antibodies recognized a cross-reactive epitope
among anti-P from different SLE patients. Plasma IgG from one healthy adult was
depleted of pepsin agglutinators and generic anti-F(ab')2 antibodies by
adsorption with an affinity column prepared with normal IgG F(ab')2. Unretained
IgG bound exclusively to anti-P F(ab')2 in ELISA. Using four affinity columns, we
isolated IgG anti-Ids to anti-P antibodies from four healthy adults. These
purified anti-Ids bound to anti-P F(ab')2 from a healthy adult and SLE patients.
They did not bind to F(ab')2 fragments prepared from normal IgG or anti-dsDNA.
Ribosomal antigens blocked this anti-Id-Id interaction. Purified anti-Ids
inhibited the binding of anti-P F(ab')2 from patients to ribosomal P proteins.
SLE patients without overt anti-P antibodies also possessed IgG anti-Ids to anti
P antibodies. We conclude that IgG-inhibitory antibodies are anti-Ids to anti-P
antibodies, and are directed to public idiotopes on anti-P antibodies. These anti
Ids may be part of an Id network that regulates anti-P antibody expression, and
perhaps pathogenicity.
PMID- 9649576
TI - Natural killer cells from human immunodeficiency virus (HIV)-infected individuals
are an important source of CC-chemokines and suppress HIV-1 entry and replication
in vitro.
AB - Macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on
activation, normal T cell expressed and secreted), which are the natural ligands
of the CC-chemokine receptor CCR5, inhibit replication of MT-2- negative strains
of HIV-1 by interfering with the ability of these strains to utilize CCR5 as a
coreceptor for entry in CD4(+) cells. The present study investigates the capacity
of natural killer (NK) cells isolated from HIV-infected individuals to produce CC
chemokines and to suppress HIV replication in autologous, endogenously infected
cells as well as to block entry of MT-2-negative HIV into the CD4(+) T cell line
PM-1. NK cells freshly isolated from HIV-infected individuals had a high number
of mRNA copies for MIP-1alpha and RANTES. NK cells produced significant amounts
of RANTES, MIP-1alpha, and MIP-1beta constitutively, in response to stimulation
with IL-2 alone and when they were performing their characteristic lytic activity
(K562 killing). After CD16 cross-linking and stimulation with IL-2 or IL-15 NK
cells produced CC-chemokines to levels comparable to those produced by anti-CD3
stimulated CD8(+) T cells. Furthermore, CD16 cross-linked NK cells suppressed (49
97%) viral replication in cocultures of autologous CD8/NK-depleted PBMC to a
degree similar to that of PHA or anti-CD3-stimulated CD8(+) T cells. In 50% of
patients tested, NK-mediated HIV suppression could be abrogated by neutralizing
antibodies to MIP-1alpha, MIP-1beta and RANTES; in contrast, CD8(+) T cell
mediated suppression was not significantly overcome upon neutralization of CC
chemokines. Supernatants derived from cultures of CD16 cross-linked NK cells
stimulated with IL-2 or IL-15 dramatically inhibited entry of a MT-2-negative
strain of HIV, BaL, in the CD4(+)CCR5(+) PM-1 T cell line. These data suggest
that activated NK cells may be an important source of CC-chemokines in vivo and
may suppress HIV replication by CC-chemokine-mediated mechanisms in addition to
classic NK-mediated lytic mechanisms.
PMID- 9649577
TI - Insulin promoter factor-1 gene mutation linked to early-onset type 2 diabetes
mellitus directs expression of a dominant negative isoprotein.
AB - The homeodomain transcription factor insulin promoter factor-1 (IPF-1) is
required for development of the pancreas and also mediates glucose-responsive
stimulation of insulin gene transcription. Earlier we described a human subject
with pancreatic agenesis attributable to homozygosity for a cytosine deletion in
codon 63 of the IPF-1 gene (Pro63fsdelC). Pro63fsdelC resulted in the premature
truncation of an IPF-1 protein which lacked the homeodomain required for DNA
binding and nuclear localization. Subsequently, we linked the heterozygous state
of this mutation with type 2 diabetes mellitus in the extended family of the
pancreatic agenesis proband. In the course of expressing the mutant IPF-1 protein
in eukaryotic cells, we detected a second IPF-1 isoform, recognized by COOH- but
not NH2-terminal-specific antisera. This isoform localizes to the nucleus and
retains DNA-binding functions. We provide evidence that internal translation
initiating at an out-of-frame AUG accounts for the appearance of this protein.
The reading frame crosses over to the wild-type IPF-1 reading frame at the site
of the point deletion just carboxy proximal to the transactivation domain. Thus,
the single mutated allele results in the translation of two IPF-1 isoproteins,
one of which consists of the NH2-terminal transactivation domain and is
sequestered in the cytoplasm and the second of which contains the COOH-terminal
DNA-binding domain, but lacks the transactivation domain. Further, the COOH
terminal mutant IPF-1 isoform does not activate transcription and inhibits the
transactivation functions of wild-type IPF-1. This circumstance suggests that the
mechanism of diabetes in these individuals may be due not only to reduced gene
dosage, but also to a dominant negative inhibition of transcription of the
insulin gene and other beta cell-specific genes regulated by the mutant IPF-1.
PMID- 9649578
TI - Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function
and gene expression in cultured airway parasympathetic neurons.
AB - Viral infections increase vagally mediated reflex bronchoconstriction. Decreased
function of inhibitory M2 muscarinic receptors on the parasympathetic nerve
endings is likely to contribute to increased acetylcholine release. In this
study, we used cultured airway parasympathetic neurons to determine the effects
of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release,
inhibitory M2 receptor function, and M2 receptor gene expression. In control
cultures, electrically stimulated acetylcholine release increased when the
inhibitory M2 receptors were blocked using atropine (10(-)5 M) and decreased when
these receptors were stimulated using methacholine (10(-)5 M). Acetylcholine
release was increased by viral infection and by treatment with IFN-gamma (300
U/ml). In these cells, atropine did not further potentiate, nor did methacholine
inhibit, acetylcholine release, suggesting decreased inhibitory M2 receptor
function and/or expression. Using a competitive reverse transcription-polymerase
chain reaction method, we demonstrated that M2 receptor gene expression was
decreased by more that an order of magnitude both by virus infection and by
treatment with IFN. Thus, viral infections may increase vagally mediated
bronchoconstriction both by directly inhibiting M2 receptor gene expression and
by causing release of IFN-gamma which inhibits M2 receptor gene expression.
PMID- 9649579
TI - Regulation of acetylcholine receptor gene expression in human myasthenia gravis
muscles. Evidences for a compensatory mechanism triggered by receptor loss.
AB - Myasthenia gravis (MG) is a neuromuscular disorder mediated by antibodies
directed against the acetylcholine receptor (nAChR) resulting in a functional
nAChR loss. To analyze the molecular mechanisms involved at the muscular target
site, we studied the expression of nAChR subunits in muscle biopsy specimens from
MG patients. By using quantitative PCR with an internal standard for each
subunit, we found that the levels of beta-, delta-, and epsilon-subunit mRNA
coding for the adult nAChR were increased in severely affected MG patients,
matching our previous data on the alpha-subunit. Messenger levels were highly
variable in MG patients but not in controls, pointing to individual factors
involved in the regulation of nAChR genes. The fetal subunit (gamma-chain)
transcripts were almost undetectable in the extrajunctional region of MG muscle,
suggesting that gene regulation in MG differs from that in the denervation model,
in which nAChR gamma-subunit mRNA is reexpressed. Nicotinic AChR loss mediated by
monoclonal anti-nAChR antibodies in both the TE671 muscle cell line and cultured
normal human myotubes induces a similar increase in beta- alphand delta-subunit
mRNA levels, suggesting the existence of a new muscular signaling pathway system
coupled to nAChR internalization and independent of muscle electrical activity.
These data demonstrate the existence of a compensatory mechanism regulating the
expression of the genes coding for the adult nAChR in patients with MG.
PMID- 9649580
TI - The voltage dependence of a cloned mammalian renal type II Na+/Pi cotransporter
(NaPi-2).
AB - The voltage dependence of the rat renal type II Na+/Pi cotransporter (NaPi-2) was
investigated by expressing NaPi-2 in Xenopus laevis oocytes and applying the two
electrode voltage clamp. In the steady state, superfusion with inorganic
phosphate (Pi) induced inward currents (Ip) in the presence of 96 mM Na+ over the
potential range -140 = V = +40 mV. With Pi as the variable substrate, the
apparent affinity constant (KmPi) was strongly dependent on Na+, increasing
sixfold for a twofold reduction in external Na+. KmPi increased with depolarizing
voltage and was more sensitive to voltage at reduced Na+. The Hill coefficient
was close to unity and the predicted maximum Ip (Ipmax) was 40% smaller at 50 mM
Na+. With Na+ as the variable substrate, KmNa was weakly dependent on both Pi and
voltage, the Hill coefficient was close to 3 and Ipmax was independent of Pi at
50 mV. The competitive inhibitor phosphonoformic acid suppressed the steady state
holding current in a Na+-dependent manner, indicating the existence of uncoupled
Na+ slippage. Voltage steps induced pre-steady state relaxations typical for Na+
coupled cotransporters. NaPi-2-dependent relaxations were quantitated by a
single, voltage-dependent exponential. At 96 mM Na+, a Boltzmann function was fit
to the steady state charge distribution (Q-V) to give a midpoint voltage (V0.5)
in the range -20 to -50 mV and an apparent valency of approximately 0.5 e-. V0.5
became more negative as Na+ was reduced. Pi suppressed relaxations in a dose
dependent manner, but had little effect on their voltage dependence. Reducing
external pH shifted V0.5 to depolarizing potentials and suppressed relaxations in
the absence of Na+, suggesting that protons interact with the unloaded carrier.
These findings were incorporated into an ordered kinetic model whereby Na+ is the
first and last substrate to bind, and the observed voltage dependence arises from
the unloaded carrier and first Na+ binding step.
PMID- 9649581
TI - Patch clamp on the luminal membrane of exocrine gland acini from frog skin (Rana
esculenta) reveals the presence of cystic fibrosis transmembrane conductance
regulator-like Cl- channels activated by cyclic AMP.
AB - Chloride channels in the luminal membrane of exocrine gland acini from frog skin
(Rana esculenta) constituted a single homogeneous population. In cell-attached
patches, channels activated upon exposure to isoproterenol, forskolin, or
dibutyryl-cAMP and isobutyl-1-methyl-xanthine rectified in the outward direction
with a conductance of 10.0 +/- 0.4 pS for outgoing currents. Channels in
stimulated cells reversed at 0 mV applied potential, whereas channels in
unstimulated cells reversed at depolarized potentials (28.1 +/- 6.7 mV),
indicating that Cl- was above electrochemical equilibrium in unstimulated, but
not in stimulated, cells. In excised inside-out patches with 25 mM Cl- on the
inside, activity of small (8-pS) linear Cl--selective channels was dependent upon
bath ATP (1.5 mM) and increased upon exposure to cAMP-dependent protein kinase.
The channels displayed a single substate, located just below 2/3 of the full
channel amplitude. Halide selectivity was identified as PBr > PI > PCl from the
Goldman equation; however, the conductance sequence when either halide was
permeating the channel was GCl > GBr >> GI. In inside-out patches, the channels
were blocked reversibly by 5-nitro-2-(3-phenylpropylamino)benzoic acid,
glibenclamide, and diphenylamine-2-carboxylic acid, whereas 4, 4
diisothiocyanatostilbene-2,2-disulfonic acid blocked channel activity completely
and irreversibly. Single-channel kinetics revealed one open state (mean lifetime
= 158 +/- 72 ms) and two closed states (lifetimes: 12 +/- 4 and 224 +/- 31 ms,
respectively). Power density spectra had a double-Lorentzian form with corner
frequencies 0.85 +/- 0.11 and 27.9 +/- 2.9 Hz, respectively. These channels are
considered homologous to the cystic fibrosis transmembrane conductance regulator
Cl- channel, which has been localized to the submucosal skin glands in Xenopus by
immunohistochemistry (Engelhardt, J.F., S.S. Smith, E. Allen, J.R. Yankaskas,
D.C. Dawson, and J.M. Wilson. 1994. Am. J. Physiol. 267: C491-C500) and, when
stimulated by cAMP-dependent phosphorylation, are suggested to function in
chloride secretion.
PMID- 9649582
TI - Properties of a novel pH-dependent Ca2+ permeation pathway present in male germ
cells with possible roles in spermatogenesis and mature sperm function.
AB - Rises of intracellular Ca2+ ([Ca2+]i) are key signals for cell division,
differentiation, and maturation. Similarly, they are likely to be important for
the unique processes of meiosis and spermatogenesis, carried out exclusively by
male germ cells. In addition, elevations of [Ca2+]i and intracellular pH (pHi) in
mature sperm trigger at least two events obligatory for fertilization:
capacitation and acrosome reaction. Evidence implicates the activity of Ca2+
channels modulated by pHi in the origin of these Ca2+ elevations, but their
nature remains unexplored, in part because work in individual spermatozoa are
hampered by formidable experimental difficulties. Recently, late spermatogenic
cells have emerged as a model system for studying aspects relevant for sperm
physiology, such as plasmalemmal ion fluxes. Here we describe the first study on
the influence of controlled intracellular alkalinization on [Ca2+]i on identified
spermatogenic cells from mouse adult testes. In BCECF [(2',7')-bis(carboxymethyl)
(5, 6)-carboxyfluorescein]-AM-loaded spermatogenic cells, a brief (30-60 s)
application of 25 mM NH4Cl increased pHi by approximately 1.3 U from a resting
pHi approximately 6.65. A steady pHi plateau was maintained during NH4Cl
application, with little or no rebound acidification. In fura-2-AM-loaded cells,
alkalinization induced a biphasic response composed of an initial [Ca2+]i drop
followed by a two- to threefold rise. Maneuvers that inhibit either Ca2+ influx
or intracellular Ca2+ release demonstrated that the majority of the Ca2+ rise
results from plasma membrane Ca2+ influx, although a small component likely to
result from intracellular Ca2+ release was occasionally observed. Ca2+ transients
potentiated with repeated NH4Cl applications, gradually obliterating the initial
[Ca2+]i drop. The pH-sensitive Ca2+ permeation pathway allows the passage of
other divalents (Sr2+, Ba2+, and Mn2+) and is blocked by inorganic Ca2+ channel
blockers (Ni2+ and Cd2+), but not by the organic blocker nifedipine. The
magnitude of these Ca2+ transients increased as maturation advanced, with the
largest responses being recorded in testicular sperm. By extrapolation, these
findings suggest that the pH-dependent Ca2+ influx pathway could play significant
roles in mature sperm physiology. Its pharmacology and ion selectivity suggests
that it corresponds to an ion channel different from the voltage-gated T-type
Ca2+ channel also present in spermatogenic cells. We postulate that the Ca2+
permeation pathway regulated by pHi, if present in mature sperm, may be
responsible for the dihydropyridine-insensitive Ca2+ influx required for
initiating the acrosome reaction and perhaps other important sperm functions.
PMID- 9649583
TI - Interactions of a reversible ryanoid (21-amino-9alpha-hydroxy-ryanodine) with
single sheep cardiac ryanodine receptor channels.
AB - The binding of ryanodine to a high affinity site on the sarcoplasmic reticulum
Ca2+-release channel results in a dramatic alteration in both gating and ion
handling; the channel enters a high open probability, reduced-conductance state.
Once bound, ryanodine does not dissociate from its site within the time frame of
a single channel experiment. In this report, we describe the interactions of a
synthetic ryanoid, 21-amino-9alpha-hydroxy-ryanodine, with the high affinity
ryanodine binding site on the sheep cardiac sarcoplasmic reticulum Ca2+-release
channel. The interaction of 21-amino-9alpha-hydroxy-ryanodine with the channel
induces the occurrence of a characteristic high open probability, reduced
conductance state; however, in contrast to ryanodine, the interaction of this
ryanoid with the channel is reversible under steady state conditions, with dwell
times in the modified state lasting seconds. By monitoring the reversible
interaction of this ryanoid with single channels under voltage clamp conditions,
we have established a number of novel features of the ryanoid binding reaction.
(a) Modification of channel function occurs when a single molecule of ryanoid
binds to the channel protein. (b) The ryanoid has access to its binding site only
from the cytosolic side of the channel and the site is available only when the
channel is open. (c) The interaction of 21-amino-9alpha-hydroxy-ryanodine with
its binding site is influenced strongly by transmembrane voltage. We suggest that
this voltage dependence is derived from a voltage-driven conformational
alteration of the channel protein that changes the affinity of the binding site,
rather than the translocation of the ryanoid into the voltage drop across the
channel.
PMID- 9649584
TI - Interactions between multiple phosphorylation sites in the inactivation particle
of a K+ channel. Insights into the molecular mechanism of protein kinase C
action.
AB - Protein kinase C inhibits inactivation gating of Kv3.4 K+ channels, and at least
two NH2-terminal serines (S15 and S21) appeared involved in this interaction (.
Neuron. 13:1403-1412). Here we have investigated the molecular mechanism of this
regulatory process. Site-directed mutagenesis (serine --> alanine) revealed two
additional sites at S8 and S9. The mutation S9A inhibited the action of PKC by
approximately 85%, whereas S8A, S15A, and S21A exhibited smaller reductions (41,
35, and 50%, respectively). In spite of the relatively large effects of
individual S --> A mutations, simultaneous mutation of the four sites was
necessary to completely abolish inhibition of inactivation by PKC. Accordingly, a
peptide corresponding to the inactivation domain of Kv3.4 was phosphorylated by
specific PKC isoforms, but the mutant peptide (S[8,9,15,21]A) was not.
Substitutions of negatively charged aspartate (D) for serine at positions 8, 9,
15, and 21 closely mimicked the effect of phosphorylation on channel
inactivation. S --> D mutations slowed the rate of inactivation and accelerated
the rate of recovery from inactivation. Thus, the negative charge of the
phosphoserines is an important incentive to inhibit inactivation. Consistent with
this interpretation, the effects of S8D and S8E (E = Glu) were very similar, yet
S8N (N = Asn) had little effect on the onset of inactivation but accelerated the
recovery from inactivation. Interestingly, the effects of single S --> D
mutations were unequal and the effects of combined mutations were greater than
expected assuming a simple additive effect of the free energies that the single
mutations contribute to impair inactivation. These observations demonstrate that
the inactivation particle of Kv3.4 does not behave as a point charge and suggest
that the NH2-terminal phosphoserines interact in a cooperative manner to disrupt
inactivation. Inspection of the tertiary structure of the inactivation domain of
Kv3.4 revealed the topography of the phosphorylation sites and possible
interactions that can explain the action of PKC on inactivation gating.
PMID- 9649585
TI - Macroscopic Na+ currents in the "Nonconducting" Shaker potassium channel mutant
W434F.
AB - C-type inactivation in Shaker potassium channels inhibits K+ permeation. The
associated structural changes appear to involve the outer region of the pore.
Recently, we have shown that C-type inactivation involves a change in the
selectivity of the Shaker channel, such that C-type inactivated channels show
maintained voltage-sensitive activation and deactivation of Na+ and Li+ currents
in K+-free solutions, although they show no measurable ionic currents in
physiological solutions. In addition, it appears that the effective block of ion
conduction produced by the mutation W434F in the pore region may be associated
with permanent C-type inactivation of W434F channels. These conclusions predict
that permanently C-type inactivated W434F channels would also show Na+ and Li+
currents (in K+-free solutions) with kinetics similar to those seen in C-type
inactivated Shaker channels. This paper confirms that prediction and demonstrates
that activation and deactivation parameters for this mutant can be obtained from
macroscopic ionic current measurements. We also show that the prolonged Na+ tail
currents typical of C-type inactivated channels involve an equivalent
prolongation of the return of gating charge, thus demonstrating that the kinetics
of gating charge return in W434F channels can be markedly altered by changes in
ionic conditions.
PMID- 9649586
TI - Vitamin A is required for regulation of polymeric immunoglobulin receptor (pIgR)
expression by interleukin-4 and interferon-gamma in a human intestinal epithelial
cell line.
AB - The secretory immunoglobulin A (IgA) antibody response to infections of mucosal
surfaces requires transport of IgA from the basal to apical surface of mucosal
epithelial cells by a specific transport protein, the polymeric immunoglobulin
receptor (pIgR). We have tested the hypothesis that the vitamin A metabolite all
trans retinoic acid (RA) is required for the regulation of pIgR expression by the
cytokines interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in HT-29 cells, a
well-differentiated human epithelial cell line derived from a colonic carcinoma.
pIgR expression is upregulated by IFN-gamma and IL-4 when HT-29 cells are grown
in normal media, but this upregulation was significantly lower when cells were
grown in vitamin A-depleted media. Treatment with RA at concentrations from 10(
9) to 10(-5) mol/L restored normal levels of pIgR expression. The percentages of
cells expressing cell-surface pIgR after 24, 48 and 72 h of treatment with RA, IL
4 and IFN-gamma were 66 +/- 10, 90 +/- 5 and 92 +/- 1, respectively,
significantly higher than the percentages seen without RA treatment, which were
32 +/- 2.3, 72 +/- 1.2 and 30 +/- 7, respectively. In addition, the intensity of
fluorescence of pIgR-positive cells was significantly higher in the RA-treated
cultures than in the cultures without RA treatment. Similarly, pIgR mRNA levels
(adjusted for beta-actin mRNA levels) in RA-supplemented cultures were 404, 105
and 949% higher at 24, 48 and 72 h, respectively, than were pIgR mRNA levels in
identical cultures grown in the absence of RA. These data indicate that RA
strongly interacts with IL-4 and IFN-gamma to regulate pIgR expression in HT-29
cells, suggesting that vitamin A may be required for proper in vivo regulation of
IgA transport in response to mucosal infections.
PMID- 9649587
TI - Cellular glutathione peroxidase is the mediator of body selenium to protect
against paraquat lethality in transgenic mice.
AB - The antioxidative role of Se-dependent cellular glutathione peroxidase (EC
1.11.1.9, GPX1) in vivo has not been established. Our objective was to determine
the effects of GPX1 knockout or overexpression on the susceptibility of mice to
paraquat toxicity and the contributions of GPX1, compared with other
selenoproteins and vitamin E, to body defenses against such acute oxidative
stress. Four experiments were conducted using 111 GPX1 knockout or overexpressing
mice and the respective controls. Mice were fed diets supplemented with Se (as
sodium selenite) at 0-0.4 mg/kg and/or all-rac-alpha-tocopheryl acetate at 0-75
mg/kg before intraperitoneal injections of 12.5, 50 or 125 mg paraquat/kg body
weight. All mice that received 50 or 125 mg paraquat/kg died spontaneously, and
the survival time of mice was (independent of dietary levels of Se per se or
alpha-tocopheryl acetate) solely a function of tissue GPX1 activity (P < 0.001).
Severe acute pulmonary interstitial necrosis was found only in the GPX1
overexpressing mice and the controls that had extended survival time.
Thiobarbituric acid reacting substances in postmortem liver inversely correlated
with the tissue GPX1 activity and dietary levels of Se and/or alpha-tocopheryl
acetate. In contrast, all mice that received 12.5 mg paraquat/kg survived and
were killed 2 wk after the injection for tissue collection. Compared with the
saline injection, this low dose of paraquat resulted in greater (P < 0.001) liver
and lung F2-isoprostanes in both the GPX1 knockout mice and the controls.
However, there was no difference in plasma alanine transaminase (EC 2.6.1.2)
activity or overt injuries in liver, lung and kidney in either group. Our data
indicate that GPX1 is the major, if not the only, metabolic form of body Se that
protects mice against the lethal oxidative stress caused by high levels of
paraquat; it seems less important, however, in protecting mice against the
moderate oxidative stress by the low level of paraquat.
PMID- 9649588
TI - Iron deficiency reduces the hydrolysis of cell membrane phosphatidyl inositol-4,5
bisphosphate during splenic lymphocyte activation in C57BL/6 mice.
AB - Iron deficiency impairs lymphocyte proliferation in humans and laboratory animals
by unknown mechanisms. In this study, we investigated whether this alteration can
be attributed in part to impaired hydrolysis of cell membrane phosphatidyl
inositol-4, 5-bisphosphate (PIP2), a required early event of T-lymphocyte
activation. The study involved 46 iron-deficient (ID), 26 control (C) and 23 pair
fed (PF) mice, and ID mice that were repleted for 3 (n = 16), 7 (n = 17) or 14 d
(n = 18). Mice were killed after 40-63 d (mean, 48 d) of consuming the test diet
(0.09 mmol/kg iron) or the control diet (0.9 mmol/kg). The mean (+/-SEM)
hemoglobin concentrations were 57 +/- 16.7, 176 +/- 2.6 and 181 +/- 9.7 g/L for
ID, C and PF groups, respectively. After splenic lymphocytes were labeled in
vitro with 3H-myoinositol for 3 h, PIP2 hydrolysis was estimated by measuring the
radioactivity recovered as a mixture of inositol mono-, di- and triphosphate (IP)
from concanavalin A (0, 1, 2.5, 5 and 10 mg/L) activated cells. Although cells
from ID mice and those from mice repleted for 3 d incorporated slightly more
radioactivity in cellular phospholipids than did cells from C or PF mice, less (P
< 0.005) was recovered as IP than in controls, suggesting impaired conversion of
the precursor to PIP2. At almost all incubation periods (10-120 min) and mitogen
concentrations, the rate of PIP2 hydrolysis expressed as the ratio of
radioactivity obtained in Con A-treated to untreated cells was significantly (P <
0.05) reduced in cells from ID mice compared with those obtained from C and PF
mice. For cells that were activated for 60 min or less, iron repletion for 14 d
significantly (P < 0.05) improved the rate of PIP2 hydrolysis. PIP2 hydrolysis
positively and significantly (P < 0.05) correlated (r = 0.27-0.56) with
indicators of iron status. Mitogenic response was also significantly (P < 0.05)
reduced in ID but not PF mice, and it was corrected by iron repletion for 3, 7 or
14 d. Lymphocyte proliferation positively (r = 0.27-0.37, P < 0.01) correlated
with indices of iron status and IP ratios. The data suggest that reduced PIP2
hydrolysis contributes to impaired blastogenesis in iron deficiency.
PMID- 9649589
TI - Highly purified soybean protein is not hypocholesterolemic in rats but stimulates
cholesterol synthesis and excretion and reduces polyunsaturated fatty acid
biosynthesis.
AB - The specific effects of soybean protein on lipid metabolism were determined with
highly purified soybean protein. At 5 wk of age, growing rats were fed diets
containing 20% highly purified soybean protein or casein supplemented or not with
0.1% cholesterol for 2 mo. Plasma and liver lipid composition, fecal steroid
excretion and several hepatic enzyme activities were measured. There were no
significant dietary protein-related differences in plasma and liver cholesterol
concentrations. When diets were cholesterol free, highly purified soybean protein
stimulated fecal neutral and acidic steroid excretion associated with
concomitantly higher hydroxy methylglutaryl CoA (HMG-CoA) reductase activity, but
lower cholesterol 7alpha-hydroxylase activity. Soybean protein lowered the
linoleate desaturation index [20:4(n-6)/18:2(n-6)] in liver microsomal lipids and
phospholipids. This may have been due to the reduced microsomal Delta6(n-6)
desaturase activity in rats fed soybean protein, whereas Delta5(n-6) desaturase
activity did not differ between groups fed the two proteins. Cholesterol
supplementation (0.1%) did not affect plasma cholesterol but increased liver
cholesterol and triacylglycerol concentrations and reduced HMG-CoA reductase
activity; this latter effect was greatest in rats fed soybean protein.
Cholesterol 7alpha-hydroxylase activity, however, was diminished only in rats fed
casein. Desaturase activities, and particularly Delta5(n-6) activity, were
lowered by cholesterol supplementation in rats fed both protein diets, including
a significantly lower 20:4(n-6)/18:2(n-6) ratio in liver microsomal lipids and
liver phospholipids. Thus although dietary proteins have no effect on serum
cholesterol in rats, they affect enzyme activities involved in cholesterol
metabolism and fatty acid desaturation.
PMID- 9649590
TI - Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression
in rats.
AB - This study investigated whether interleukin-1alpha-induced metallothionein gene
expression is affected by zinc deficiency. Weaning male rats were fed a zinc
deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg;
controls for the diet included pair-fed (PF) and ad libitum consumption groups
(AL)] for 4 wk. All rats except those that served as controls for interleukin
1alpha administration, (injected with vehicle and killed at 0 h) were then
injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and
killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF
rats, zinc depletion significantly reduced zinc concentrations in plasma and
liver but not in kidney or intestine, and significantly reduced hepatic, renal,
and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse
transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection
reduced plasma zinc concentration and enhanced liver zinc concentration, but did
not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was
significantly elevated by interleukin-1alpha in liver, kidney and intestine of
all groups; the levels in liver and kidney of ZD rats 6 h after the injection
were significantly higher than those of AL or PF rats. Liver metallothionein
protein levels were enhanced after interleukin-1alpha injection in both AL and ZD
rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of
interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no
differences in renal or intestinal tissues among groups before interleukin-1alpha
challenge. In conclusion, zinc deficiency induces upregulation of metallothionein
1 gene expression in response to interleukin-1alpha challenge in rats.
PMID- 9649591
TI - Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide
and insulin-like growth factor I as putative mediators of the hypolipidemic
effect of oligofructose in rats.
AB - The addition of oligofructose as a dietary fiber decreases the serum
concentration and the hepatic release of VLDL-triglycerides in rats. Because
glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e.,
glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1
(GLP-1)]) are factors involved in the metabolic response to nutrients, this paper
analyzes their putative role in the hypolipidemic effect of oligofructose. Male
Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30
d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of
rats after eating. GIP and GLP-1 contents were also assayed in small intestine
and cecal extracts, respectively. A glucose tolerance test was performed in food
deprived rats. Serum insulin level was significantly lower in oligofructose-fed
rats both after eating and in the glucose tolerance test, whereas glycemia was
lower only in the postprandial state. IGF-I serum level did not differ between
groups. GIP concentration was significantly higher in the serum of oligofructose
fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we
have shown that cecal proliferation induced by oligofructose leads to an increase
in GLP-1 concentration. This latter incretin could be involved in the maintenance
of glycemia despite a lower insulinemia in the glucose tolerance test in
oligofructose-fed rats. We discuss also the role of hormonal changes in the
antilipogenic effect of oligofructose.
PMID- 9649592
TI - Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in
cynomolgus monkeys in a dose-dependent manner.
AB - To examine the mechanism(s) underlying the cholesterolemic response to dietary
cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism
was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of
total energy as fat. At each dietary fat level, the same group of monkeys was
sequentially fed three dietary cholesterol concentrations as egg yolk in the
following sequence: low (0.01 mg/kJ), medium (0.03 mg/kJ) and high (0.05 mg/kJ)
for 30, 32 and 24 wk, respectively. Dietary polyunsaturated and monounsaturated
fatty acids were the same in the two groups; the 6% difference in fat was due to
the saturated fatty acids, 12:0 and 14:0. Serum total cholesterol, LDL
cholesterol and LDL apolipoprotein B concentrations increased (P < 0.05) with
dietary cholesterol in a dose-dependent manner in both fat groups. These
elevations were the result of generally increasing LDL apolipoprotein B
production rates, concomitant with reduced LDL apolipoprotein B fractional
clearance at the high cholesterol intake. Serum HDL cholesterol and HDL
apolipoprotein A-I concentrations were not affected in a consistent manner. These
results demonstrate that cynomolgus monkeys are hyperresponsive to dietary
cholesterol compared with humans, suggesting that this model may be useful in
identifying metabolic and genetic predictors for hyperresponsiveness to dietary
cholesterol in humans as well as assessing the metabolic heterogeneity of
responses to dietary cholesterol.
PMID- 9649593
TI - Food deprivation changes peroxisomal beta-oxidation activity but not catalase
activity during postnatal development in pig tissues.
AB - Peroxisomal beta-oxidation and catalase activity were investigated in liver,
kidney and heart from pigs at the following timepoints: within 0.5 h after birth
(0 h, unfed) and at 24 h (suckled or unsuckled), 10 d (suckled or 24-h food
deprived), 21 d (suckled or 24-h food-deprived) and 5 mo (overnight food
deprived). In liver, peroxisomal beta-oxidation increased about twofold at 24 h
for suckled pigs (P < 0.001) but did not change for unsuckled pigs. The rate was
further increased in 21-d-old pigs compared with 0- (P < 0. 001) or 24-h-old (P <
0.05) pigs, but was lower at 5 mo than at 10 or 21 d (P < 0.01). The rate was
higher for food-deprived pigs than suckled pigs at 10 d (P < 0.001) of age. In
kidney, peroxisomal beta-oxidation was unchanged during the first 24 h but was
higher (P < 0.05) at 10 d for suckled pigs and at 21 d than at 0 h. Nutritional
state did not influence renal peroxisomal beta-oxidation. In heart, peroxisomal
beta-oxidation did not change with age or nutritional state. The developmental
pattern of fatty acyl-CoA oxidase activity was similar to that of peroxisomal
beta-oxidation in each tissue. Developmental increases of peroxisomal beta
oxidation were greater than those for first-cycle peroxisomal beta-oxidation
reported earlier, suggesting that peroxisomal beta-oxidation became more complete
in older pigs. Catalase activity did not change during the first 24 h after birth
but then increased 10.5-, 2.9-fold and 33% at 10 d in liver, kidney and heart,
respectively. The concentration of catalase mRNA was only 1.1- and 1. 3-fold
higher at 10 d than at 24 h in liver and kidney, respectively. Catalase activity
was not affected by food deprivation. We concluded the following: 1) peroxisomal
beta-oxidation develops rapidly after birth and may be important for piglets to
oxidize milk fatty acids; 2) food is required for the initial induction after
birth; and 3) rapidly increased catalase activity during the first 10 d of life
resulted from both pretranslational and post-translational regulation.
PMID- 9649594
TI - Urinary iodine excretion is the most appropriate outcome indicator for iodine
deficiency at field conditions at district level.
AB - To empower local authorities to plan and evaluate adequate interventions,
appropriate iodine deficiency disorders (IDD) indicators need to be identified.
The aim of this study was to describe the magnitude and severity of IDD with
different outcome indicators and associate them with functional indicators.
Schoolchildren (n = 544) aged 8-10 y were assessed in 11 villages within five
subdistricts of Malang District, East Java, Indonesia. Outcome indicators of IDD
were goiter size as measured by palpation and ultrasonography (USG), urinary
iodine excretion (UIE) and serum thyroid stimulating hormone (TSH) concentration
in blood as well as functional indicators such as intellectual performance (IQ:
Catell's Culture Fair Intelligence Test) and anthropometric indices. The total
goiter rate (TGR) measured by palpation and USG were 35.7 and 54.4%,
respectively. Based on UIE and TSH, the prevalence of iodine deficiency was 63.7
and 3.4%, respectively. In individuals, goiter, thyroid volume and UIE were
associated significantly (r = -0.35; P < 0.001 and r = -0.30; P = 0.02
respectively). Among villages, TGR measured by palpation was significantly
correlated with thyroid volume (r = 0.61; P = 0.045) and UIE (r = 0.68; P =
0.021), whereas TSH was not significantly associated with any of the observed
indicators in individuals or groups. Multiple regression analysis showed that USG
(beta = -0.67; P < 0.001) and UIE (beta = 4.39; P = 0.008) related significantly
with cognitive performance (IQ). The associations between IDD indicators and
cognitive performance and height-for-age Z scores suggest that socioeconomically
advantaged children had better iodine status. We suggest that UIE is the best
indicator for local authorities to assess iodine deficiency.
PMID- 9649595
TI - Eating from a shared plate affects food consumption in vitamin A-deficient Nepali
children.
AB - This case-control study evaluates the relationship between shared-plate eating
behavior in young Nepali children (aged 1-6 y) and risk of vitamin A deficiency.
Day-long observations of dietary practices were conducted on 7 d over a 15-mo
period in 162 households: 81 households with a child with a known history of mild
xerophthalmia (cases) were matched with 81 having a non-xerophthalmic child of
similar age (controls). Shared-plate eating occurred in 25% of all feeding
episodes and at least once in 65% of all days observed. Overall, children
engaging in shared-plate eating were significantly more likely to consume grains,
vegetables, carotenoid-rich vegetables, pulses, fruits, meats and fish, and dairy
products and had significantly larger portion sizes for grains, vegetables,
fruits, pulses and dairy products, compared with children who ate alone. In
general, feeding behaviors between case and control children tended to be
similar. However, shared-plate feeding episodes among case children were
significantly less likely to include meats or fish [odds ratio (OR) = 0.5,
confidence interval (CI) = 0.3-0.8], dairy products (OR = 0.6, CI = 0.4-0.9) or
pulses (OR = 0.7, CI = 0.5-1.0). Individual-plate feeding episodes among case
children were more likely to include vegetables (OR = 1.3, CI = 1.0-1.6) than
those of control children. Case children were more likely to share a plate with a
male adult (OR = 1.7, CI = 1.0-2.8), but less likely to eat from a plate shared
with females of any age compared with controls (female adult: OR = 0.6, CI = 0.4
0.9; female child: OR = 0.6, CI = 0.4-1.0). Shared-plate eating may benefit a
young child's dietary intake, but the identity of the food sharer may modify this
influence.
PMID- 9649596
TI - The NCHS reference and the growth of breast- and bottle-fed infants.
AB - The current international growth reference, the National Center for Health
Statistics (NCHS) reference, is widely used to compare the nutritional status of
populations and to assess the growth of individual children throughout the world.
Recently, concerns were raised regarding the adequacy of this reference for
assessing the growth of breast-fed infants. We used the NCHS reference to
evaluate infant growth in one of the most developed areas of Brazil. Infants who
were exclusively or predominantly breast-fed for the first 4-6 mo, and partially
breast-fed thereafter, grew more rapidly than the NCHS reference in weight and
length during the first 3 mo, but appeared to falter thereafter. The average
growth of all infants, regardless of feeding pattern, was faster than the NCHS
reference until approximately 6 mo, after which their growth became slower than
that of the NCHS sample. To substantiate this finding, the NCHS growth curves
were then compared with growth data of breast-fed infants in developed countries
from pooled published studies, formula-fed North American and European infants
and predominantly bottle-fed U.S. infants monitored by the Centers for Disease
Control and Prevention (CDC) Pediatric Surveillance System. In all three cases,
weights showed the same pattern as the Brazilian infants-higher than NCHS in the
early months but an apparent decline thereafter. The pattern for length gain was
similar but less marked. Breast-fed infants showed more pronounced declines than
those who were predominantly bottle-fed. These findings suggest that the infancy
portion of the NCHS reference does not adequately reflect the growth of either
breast-fed or artificially fed infants. This probably results from
characteristics of the original sample and from inadequate curve-fitting
procedures. The development of an improved international growth reference that
reflects the normal infant growth pattern is indicated.
PMID- 9649597
TI - Sodium iron EDTA [NaFe(III)EDTA] as a food fortificant does not influence
absorption and urinary excretion of manganese in healthy adults.
AB - NaFe(III)EDTA is a promising iron (Fe) compound for food fortification programs
because of its high Fe bioavailability from meals containing dietary inhibitors
of Fe absorption such as phytic acid. However, this Fe compound is not currently
used in any large-scale fortification program because of concern over its
possible negative influence on the metabolism of other essential minerals or its
possible influence on the absorption of potentially toxic elements, such as
manganese (Mn). In this study, Mn absorption and urinary excretion were studied
in adults after intake of an Fe-fortified weaning cereal labeled with 54Mn. In a
crossover design, the fortification of the weaning cereal with Fe as NaFeEDTA was
compared with ferrous sulfate. Manganese absorption was measured by extrapolation
from whole-body retention data 10-30 d after intake, and urinary excretion of
54Mn was measured over 7 d. No significant differences in 54Mn absorption or
urinary excretion were found; 1.1 +/- 0.15 and 0.91 +/- 0.35% of the ingested
dose was absorbed from the cereal fortified with NaFe(III)EDTA and FeSO4,
respectively. Urinary excretion of 54Mn was very low; the total radioactivity in
urine represented 1.1 +/- 0.55% of the absorbed dose with NaFe(III)EDTA and 0.72
+/- 0.53% of the absorbed dose with FeSO4. Until now, Fe-fortification programs
have met with only limited success. The introduction of NaFeEDTA as a food
fortificant could be a useful tool to provide bioavailable Fe to vulnerable
groups in the population and thus aid in combating Fe deficiency.
PMID- 9649598
TI - Plasma lipid response to hypolipidemic diets in young healthy non-obese men
varies with body mass index.
AB - Lipid response to dietary fat is highly variable among individuals of a
population. The aim of this study was to establish whether being overweight is
one of the factors that determines this response. Forty-one non-obese healthy men
were divided into two groups according to body mass index as follows: controls,
<25 kg/m2; overweight, >25 kg/m2 but <30 kg/m2. After consuming a saturated fat
rich diet (SAT diet: 38% fat, 20% saturated) for 4 wk, subjects were switched to
a low fat diet [National Cholesterol Education Program (NCEP)-I diet: 28% fat,
10% saturated] for 4 wk and then to a monounsaturated fat-rich diet (MUFA diet:
38% fat, 22% monounsaturated) for 4 wk. Data were analyzed by Student's t test
and two-way ANOVA for repeated measures. After consuming the NCEP-I diet, the
overweight subjects had a smaller decrease relative to the SAT diet period in
plasma total cholesterol [-0.30 vs. -0.67 mmol/L (-7 vs. -16%), P < 0.02] and low
density lipoprotein-cholesterol concentrations [-0.24 vs. -0.55 mmol/L (-9 vs.
21%), P < 0.04] than controls. However, in the overweight subjects, the MUFA diet
produced a greater decrease in plasma triglycerides than in the controls relative
to the SAT diet period [-0.36 vs. -0.03 mmol/L (-26 vs. -4%), P < 0.006] and to
the NCEP-I diet period [-0.29 vs. 0. 01 mmol/L (-22 vs. 1%), P < 0.01). Plasma
cholesterol concentrations changed to a lesser extent, and triglyceride
concentration to a greater extent, in overweight but non-obese young men than in
those of normal weight in response to changes in dietary fat composition. Our
data suggest that in the diet treatment of obese hyperlipemic subjects, it is
more important for them to lose weight than to change the fat composition of
their diets.
PMID- 9649599
TI - alpha-Tocopherol concentrations in plasma but not in lipoproteins fluctuate
during the menstrual cycle in healthy premenopausal women.
AB - Because premenopausal women experience cyclic fluctuations of plasma carotenoids
and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol
(A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with
a confirmed ovulatory cycle, were given a controlled diet for two consecutive
menstrual cycles. Blood was drawn during the menses, early follicular, late
follicular and luteal phases to simultaneously measure serum hormones, plasma
lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein
fractions. Plasma A-T concentrations were significantly lower during menses than
during the luteal phase by approximately 12% in each controlled diet cycle (P <
0.001). Adjustment for serum cholesterol and triglyceride concentrations did not
alter these findings. The distributions of A-T in lipoprotein cholesterol
fractions were not significantly different by menstrual phase. From 61 to 62% of
A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in
HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences
in lipoprotein cholesterol fractions by menstrual phase, except for a significant
increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late
follicular phase. Spearman rank correlations from data during the second
controlled diet month showed A-T in HDL2 in the late follicular phase was
positively correlated with HDL cholesterol in the early follicular (r = 0.88),
late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal
apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL2 cholesterol (r = 0.83).
A-T in HDL3 in the early follicular phase was negatively correlated with HDL2
cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was
correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL
was positively correlated with early follicular HDL3 cholesterol and late
follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by
phase of the menstrual cycle should be taken into consideration in future
research concerning premenopausal women and the risk of chronic disease.
PMID- 9649600
TI - Resistant proteins alter cecal short-chain fatty acid profiles in rats fed high
amylose cornstarch.
AB - The objective of this study was to examine the physiologic importance of
undigested protein on cecal fermentation in rats fed a low (LAS) and high (HAS)
amylose cornstarch. In Experiment 1, rats were fed diets containing LAS (655 g/kg
diet) with one of four protein sources: casein, rice (RP), potato (PP) or soybean
protein (SP) at 250 g/kg diet for 15 d. Apparent digestibilities of casein, RP,
SP and PP were 96, 94, 93 and 92%, respectively. In rats fed the LAS diet with
casein, acetate, propionate and succinate were the major cecal organic acids. The
succinate pools in rats fed RP or SP were significantly lower than in those fed
casein, whereas butyrate did not differ. Butyrate was significantly higher in
rats fed PP, but succinate was the same as in rats fed casein. In Experiment 2,
rats were fed diets containing HAS (200 g/kg diet) with one of the four protein
sources at 250 g/kg diet for 10 d. HAS was substituted for the same amount of
LAS. In rats fed the HAS diet, succinate was the major acid in rats fed casein;
in rats fed RP or PP, however, the pools of this acid were significantly lower
than in those fed casein, whereas butyrate was significantly higher in rats fed
RP or PP. Fecal starch excretion was significantly lower in rats fed RP or PP
than in those fed casein. In Experiment 3, rats were fed the casein-HAS diet with
graded levels of PP (0, 10, 30, 50, 100 and 250 g/kg diet) for 14 d. The PP was
substituted for the same amount of casein. Cecal butyrate was low in rats fed up
to 100 g of PP/kg diet and then rose with 250 g of PP/kg diet. In Experiment 4,
ileorectostomized rats were used and fed the same diets described in Experiment 3
for 9 d. The ileal starch/nitrogen ratio declined with increasing dietary PP, due
solely to greater nitrogen excretion, whereas starch excretion was unaffected. In
Experiment 5, rats were fed the casein-HAS diet with or without 60 g of
artificial resistant protein/kg diet for 10 d. The resistant protein (apparent
digestibility, 63%) was substituted for the same amount of casein. Rats fed the
casein-HAS diet with resistant protein had significantly greater cecal butyrate
and lower succinate than those fed the casein-HAS diet. These data show that
large bowel fermentation of starch is altered by dietary protein. They support
the hypothesis that nondigested protein, namely, resistant protein, may control
fermentation efficiency as well as the fermentation profile of HAS, possibly as a
result of a change in microflora through the change in the ratio of starch to
nitrogen in the cecum.
PMID- 9649601
TI - Regulation of branched-chain amino acid metabolism in the lactating rat.
AB - There is evidence that during lactation, uptake of the essential branched-chain
amino acids (BCAA) by mammary glands exceeds their output in milk protein. In
this study, we have measured the potential of lactating rats to catabolize BCAA.
The activity, relative protein and specific mRNA levels of the first two enzymes
in the BCAA catabolic pathway, branched-chain aminotransferase (BCAT) and
branched-chain alpha-keto acid dehydrogenase (BCKD), were measured in mammary
gland, liver and skeletal muscle obtained from rat dams at peak lactation (12 d),
from rat dams 24 h after weaning at peak lactation and from age-matched virgin
controls. Western analysis showed that the mitochondrial BCATm isoenzyme was
found in mammary gland. Comparison of lactating and control rats revealed that
tissue BCATm activity, protein and mRNA were at least 10-fold higher in mammary
tissue during lactation. Values were 1.3- to 1. 9-fold higher after 24 h of
weaning. In mammary gland of lactating rats, the BCKD complex was fully active.
In virgin controls and weaning dams, only about 20% of the complex was in the
active state. Hypertrophy of the liver and mammary gland during lactation
resulted in a 73% increase in total oxidative capacity in lactating rats. The
results are consistent with increased expression of the BCATm gene in the mammary
gland during lactation, whereas oxidation appears to be regulated primarily by
changes in activity state (phosphorylation state) of BCKD.
PMID- 9649602
TI - Accumulation of (-)-epicatechin metabolites in rat plasma after oral
administration and distribution of conjugation enzymes in rat tissues.
AB - Absorption of orally administered (-)-epicatechin (EC) in rats was studied to
obtain plasma pharmacokinetic profiles of EC metabolites. Rats were administered
172 micromol/kg body weight of EC, and blood was collected from the tail for 8 h
after administration. Seven groups of compounds possessing the basic structure of
EC were identified by using a combination of enzymatic hydrolysis, HPLC and
electron impact mass spectrometry. Metabolites were quantified with a new, simple
and sensitive method using HPLC with electrochemical detection. Ingested EC was
absorbed from the alimentary tract and was present in the rat common blood
circulation in the form of glucuronide and/or sulfate conjugates. The activity of
conjugative enzymes in rat tissues was studied. The highest activity of
glucuronosyltransferase was found in the intestinal mucosa of both of the small
and large intestine; the highest activity of phenolsulfotransferase occurred in
the liver, and that of catechol-O-methyl transferase was found in the liver and
kidney. It has been proposed that the first detoxification step of dietary EC,
namely, glucuronidation, occurs at the level of the intestinal mucosa in rats,
and EC enters the common blood circulation exclusively in the glucuronized form.
The compound is then sulfated in the liver and methylated in the liver and
kidney. Because ingested EC undergoes extensive conjugation, its biological
activities previously demonstrated in vitro may not be occurring in in vivo
systems.
PMID- 9649603
TI - Tissue stores of beta-carotene are not conserved for later use as a source of
vitamin A during compromised vitamin A status in mongolian gerbils (Meriones
unguiculatus).
AB - Vitamin A (VA) deficiency remains a serious problem in the world today. Current
approaches to preventing or treating VA deficiency, including dietary
intervention with provitamin A compounds, rely on the body converting ingested
beta-carotene (betaC) to VA. However, it is not known whether betaC that is
already in the tissues can be used as a source of VA to prevent deficiency. The
objectives of these studies were to determine whether tissue betaC stores are
converted to VA when the Mongolian gerbils have low VA status and whether
previously fed betaC is retained in the tissues for later conversion to VA. In
the first study, gerbils were prefed diets with betaC (20.3 +/- 6.2 nmol/g diet)
(+betaC) or without betaC (-betaC), and with VA [2.4 +/- 1.5 nmol/g diet (+betaC
diet) or 12.0 +/- 4.2 nmol/g diet (-betaC diet)] for 7 d, and then depleted of
both betaC and VA for up to 84 d. On d 0 after the prefeeding period, hepatic
betaC stores were 13.3 +/- 9.1 nmol. These stores were significantly lower after
28d of consuming the -VA/-betaC diet (2.16 +/- 1.7 nmol), even though the hepatic
VA concentrations did not change. In the second study, the gerbils were prefed a
VA/+betaC diet (74.3 +/- 19. 7 nmol betaC/g diet) for 7 d, and then fed a betaC
free diet either with (7.1 +/- 1.4 nmol/g) or without VA for up to 34 d. Hepatic
betaC stores after the 7-d prefeeding period were 38.1 +/- 20.6 nmol, and were
significantly higher than after 7d of consuming either a +VA/-betaC (12.4 +/-
10.8 mmol) or -VA/-betaC diet (11.4 +/- 8.0 nmol). The results from both studies
suggest that a substantial amount of hepatic betaC is rapidly lost when betaC is
eliminated from the diet and therefore is not conserved to meet later VA needs.
The presence of VA in the diet (Study 2) did not affect the rate of betaC loss
from the serum and tissues. Moreover, no evidence was found that the stored betaC
was utilized for VA. The data suggest that there may be two pools of hepatic
betaC, one that is lost rapidly and another that is lost more slowly over time,
but losses are not affected by VA status.
PMID- 9649604
TI - Feeding diets containing high levels of milk products or cellulose decrease
urease activity and ammonia production in rat intestine.
AB - Three studies were done to determine the effect of feeding diets containing high
levels of a readily fermentable carbohydrate (lactose in milk or yogurt, or pure
lactose) or an undigestible, unfermentable diluent (alpha-cellulose) on urease
(EC 3.5.1.5) activity and net ammonia production in the rat gastrointestinal (GI)
contents. Rats (170-200 g) were fed a control diet or diets containing 55% dried
milk or 55% dried yogurt, 25% lactose or 10% alpha-cellulose. Feeding diets
containing milk or yogurt decreased urease activity to approximately 11% of the
control value in the small intestine (on the basis of grams of collected contents
or total contents), and to 50% in the large intestine (only on the basis of grams
of collected contents). Feeding the diet containing 25% lactose also decreased
urease activity (on the basis of grams of collected contents or total contents)
to about 20% of the control value in the small intestine, but not (P > 0.05) in
the large intestine. Net ammonia production rate was correlated (r2 = 0.98) with
urease activity in the large intestinal contents, and the rate of ammonia
production from ureolysis represented about two thirds of the total. Feeding the
cellulose diet decreased (P < 0.05) both urease activity and net ammonia
production in the large intestine to approximately 30% of the control value.
Weights of tissue and contents of the large intestine were much higher (P < 0.01)
in rats fed diets containing milk products or lactose than in the control rats,
but were not affected by consumption of the cellulose diet. Results of our
studies indicate that feeding diets containing high levels of milk products
(lactose) or cellulose reduces urease activity and net ammonia production in the
rat intestine, and thus may be beneficial for improving animal and human health.
PMID- 9649605
TI - Intestinal fermentation lessens the inhibitory effects of phytic acid on mineral
utilization in rats.
AB - The specific effects of phytic acid (PA) and resistant starch (RS) on mineral
bioavailability, namely, Ca, Mg, Fe, Zn and Cu, were investigated in rats adapted
to semipurified diets. The diets provided either 73 g/100 g digestible wheat
starch (DS) alone, or 53 g/100 g DS plus 20 g/100 g crude potato starch (RS) and
either 0 or 1.1 g/100 g PA. A period of 3 wk was first planned to adapt the rats
to their respective diets. Compared with rats fed the DS diets, those fed the RS
diets had significant cecal hypertrophy and an accumulation of short-chain fatty
acids, together with greater cecal blood flow. RS enhanced the cecal absorption
of Ca and Mg (from 0.15 to 0.55 micromol/min for Ca, and from 0.10 to 0.35
micromol/min for Mg). Mineral balance was enhanced significantly by RS (Ca, +46%;
Mg +50%; Fe +20%; Zn, + 33% and Cu, +61%). PA had no significant effect on Ca or
Mg solubility and absorption in the cecum, and it failed to alter significantly
Ca or Mg balance. The apparent absorption of Fe, Zn and Cu was significantly
lower in rats fed the DS + PA diet than in rats fed the DS diet (Fe, -35%; Zn,
28%; and Cu, -31%). In rats adapted to the RS diet, the inhibitory effects of PA
were practically abolished and the mineral balance was restored to the control
values. We conclude that the negative effects of PA on mineral balance are
relatively minor compared with the stimulatory effect of RS.
PMID- 9649606
TI - Dietary psyllium increases fecal bile acid excretion, total steroid excretion and
bile acid biosynthesis in rats.
AB - Psyllium, a source of dietary fiber rich in soluble components results in lower
serum cholesterol concentration in several species. Suggested mechanisms for the
hypocholesterolemic effect include a greater excretion of fecal bile acids and
total steroids, and up-regulation of bile acid biosynthesis. The activity of
cholesterol 7alpha-hydroxylase (7alphaOHase), the rate limiting enzyme in bile
acid biosynthesis, is higher in rats fed 5% psyllium. Whether this higher
activity corresponds to an increase in mRNA levels has not been determined. Four
groups of 10 rats were fed a semipurified diet containing 5% cellulose (CEL;
control), 5% cellulose plus 1% cholic acid (CCA), 5% cellulose plus 2%
cholestyramine (CHY) or 5% psyllium hydrocolloid (PSY) for 3 wk. Liver
cholesterol concentration, fecal bile acid and total steroid excretion,
7alphaOHase activity and 7alphaOHase mRNA levels were measured. Liver cholesterol
content in rats fed CCA was significantly higher than in all other groups. Rats
fed CHY and PSY had significantly lower liver cholesterol content than those fed
CEL. Total fecal steroid and bile acid excretions were significantly greater in
rats fed CCA, CHY and PSY than in those fed CEL. Activities and mRNA levels of
7alphaOHase in rats fed CHY and PSY were significantly higher than in rats fed
CEL or CCA. These data indicate that feeding psyllium to rats increases fecal
bile acid and total steroid excretion as well as 7alphaOHase activity and
7alphaOHase mRNA levels.
PMID- 9649607
TI - Moderate folate depletion increases plasma homocysteine and decreases lymphocyte
DNA methylation in postmenopausal women.
AB - To determine the human folate requirement on the basis of changes in biochemical
pathways, we studied the effect of controlled folate intakes on plasma
homocysteine and lymphocyte DNA methylation and deoxynucleotide content in
healthy postmenopausal women. Eight women (49-63 y of age) were housed in a
metabolic unit and fed a low folate diet containing 56 microg/d of folate for 91
d. Folate intake was varied by supplementing 55-460 microg/d of folic acid
(pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk
at 56 microg/d, 4 wk at 111 microg/d and 3 wk at 286-516 microg/d. A subclinical
folate deficiency with decreased plasma folate was created during the first two
periods. This resulted in significantly elevated plasma homocysteine and urinary
malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also
resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA
and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into
DNA and increased DNA repair activity. The DNA hypomethylation was reversed with
286-516 microg/d of folate repletion, whereas the elevated homocysteine decreased
with 516 but not 286 microg/d of folate. The results indicate that marginal
folate deficiency may alter DNA composition and that the current RDA of 180
microg/d may not be sufficient to maintain low plasma homocysteine concentrations
of some postmenopausal women.
PMID- 9649608
TI - Dorsomedial hypothalamic lesions alter intake of an imbalanced amino acid diet in
rats.
AB - Within 3 h of ingesting an imbalanced amino acid diet (IAAD), rats show
attenuated intake. The associated conditioned taste aversion can be ameliorated
by giving the serotonin3 receptor blocker, tropisetron (TROP). A recent c-fos
study indicated that the dorsomedial hypothalamic nucleus (DMN) may be activated
2-3 h after ingestion of IAAD. In Experiment 1, DMN-lesioned rats (DMNL) or sham
operated (SHAM) rats were injected with saline (SAL) or TROP just before
introduction of IAAD. By 3 h, SAL-DMNL rats consumed more (P < 0.01) of the IAAD
than did the SAL-SHAM rats. Thereafter, over the next 21 h, the intake of the SAL
DMNL group returned to control levels. TROP treatment enhanced the intake of the
treated groups; the TROP and the lesion effect were additive (P < 0.01). By d 4
of receiving the IAAD, the DMNL groups were eating less than SHAM rats (P <
0.05). The data suggest that the DMN may be involved in the early detection of
the amino acid deficiency induced by IAAD, is not involved in the TROP effect and
is necessary for proper long-term adaptation to an IAAD.
PMID- 9649609
TI - Zinc deficiency increases hypothalamic neuropeptide Y and neuropeptide Y mRNA
levels and does not block neuropeptide Y-induced feeding in rats.
AB - Zinc deficiency reduces intake and produces an unusual approximately 3.5-d cycle
of intake in rats. The mechanism underlying the anorexia and cycling has not yet
been defined; current hypotheses suggest that alterations in amino acid
metabolism and neurotransmitter concentrations may be a part of this anorexia.
Recent reports indicate that appetite-stimulating neuropeptide Y (NPY) may be
elevated during zinc deficiency. This suggests that a resistance to NPY may exist
during zinc deficiency because NPY levels are high, yet appetite is low. The
purpose of this study was to measure NPY peptide and mRNA concentrations during
zinc deficiency in specific nuclei of the hypothalamus in which peptide and mRNA
for NPY are known to be associated with appetite, and also to determine whether
zinc-deficient rats are responsive to central infusions of NPY. Both NPY peptide
levels in the paraventricular nucleus and NPY mRNA levels in the arcuate nucleus
were higher (P < 0.05) in zinc-deficient rats than in zinc-adequate rats. When
rats were administered exogenous NPY to the paraventricular nucleus, both zinc
deficient and zinc-adequate rats responded similarly by increasing food intake.
These results suggest that NPY is elevated during zinc deficiency in an attempt
to restore normal food intake levels, rather than being reduced and thereby
contributing to the anorexia associated with zinc deficiency. During zinc
deficiency, NPY receptors are able to bind NPY and initiate an orexigenic
response.
PMID- 9649610
TI - Prenatal malnutrition-induced functional alterations in callosal connections and
in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline
synthesis during gestation.
AB - Prenatal malnutrition results in increased concentration and release of central
noradrenaline, a neurotransmitter that is an important regulator of normal
regressive events such as axonal pruning and synaptic elimination. This suggests
that some of the functional disturbances in brain induced by prenatal
malnutrition could be due at least in part to increased noradrenaline activity
that may enhance regressive events during early stages of development. To test
this hypothesis we studied whether chronic administration of alpha-methyl-p
tyrosine, an inhibitor of tyrosine hydroxylase, to rats during gestation might
prevent long-term deleterious effects of prenatal malnutrition on functional
properties of interhemispheric connections of the visual cortex, and on asymmetry
of visual evoked responses. The experiments were conducted on normal and
malnourished rats 45-50 d of age. Prenatal malnutrition was induced by
restricting the food consumption of pregnant rats to 40%, from d 8 postconception
to parturition. At birth, prenatally malnourished rats had significantly greater
whole-brain noradrenaline concentration as well as significantly enhanced
noradrenaline release in the visual cortex. At 45-50 d of age, the malnourished
group had a significantly smaller cortical area, exhibiting transcallosal evoked
responses; in addition, the amplitude of these responses was significantly
smaller. Malnourished rats showed a significant reduction of the normal
interhemispheric asymmetry of visual evoked responses. The addition of 0.3% alpha
methyl-p-tyrosine to the diet of malnourished pregnant rats during the last 2 wk
of gestation prevented functional disorders induced in the offspring by prenatal
malnutrition on interhemispheric connectivity of visual areas and on
interhemispheric bioelectrical asymmetry, probably by reducing the elevated brain
noradrenaline activity and thereby restoring the normal trophic role of this
neurotransmitter.
PMID- 9649611
TI - Calcium-deprived rats avoid sweet compounds.
AB - To characterize the link between calcium status and sweet solution intake, rats
fed a diet containing 25 mmol Ca2+/kg (Ca-25, low calcium) or 150 mmol Ca2+/kg
(Ca-150, control) were given 48-h two-bottle tests with a choice between water
and various concentrations of a nutrient (sucrose, Polycose, ethanol and/or corn
oil). Rats fed the Ca-25 diet had significantly lower sucrose intakes and
preferences over the entire range tested (10-320 g/L) even though the same
(Experiment 1), or identically treated (Experiment 2a) rats had normal Polycose
and ethanol intakes and normal (Experiment 1, 2b) or significantly greater
(Experiment 2a) corn oil intakes. In additional tests, rats fed the Ca-25 diet
had significantly lower intakes relative to rats fed the Ca-150 diet of other
sweeteners (30 mmol/L D-phenylalanine, 1 mmol/L saccharin and 0.3 mmol/L
aspartame), significantly higher intakes of 0.5 mg/L capsaicin and 300 mmol/L
monosodium glutamate, and normal intakes of 10 g/L or 80 g/L safflower oil and 10
g/L peanut oil. In a three-cup macronutrient selection experiment (Experiment 3),
calcium-deprived rats ate significantly less of a high sucrose carbohydrate
source and significantly more of a protein source than did controls. These
results suggest that calcium deficiency reduces the rat's liking for sweetness,
irrespective of the type or form of sweetener, and that this is not due to a
general reduction in energy intake.
PMID- 9649612
TI - Zinc pretreatment inhibits isotretinoin teratogenicity and induces embryonic
metallothionein in CD-1 mice.
AB - Isotretinoin (ITR), a teratogen in many species, is associated with increased
oxidative stress. Metallothionein (MT) is an important tissue antioxidant whose
concentrations are induced by zinc. To study the role of supplemental Zn as an
inducer of embryonic MT, we injected pregnant CD-1 mice subcutaneously with
saline vehicle, or 20 or 40 mg/kg Zn on gestational day (GD) 6.5. After 48 h,
embryonic MT concentrations increased in a dose-related manner (r = 0.64, P <
0.05) with Zn treatment. The possible protective role of Zn pretreatment against
ITR teratogenicity was investigated in vivo and in vitro. CD-1 mice were
pretreated with saline or Zn (20 and 40 mg/kg) on GD 8.5 and 9.5. ITR was
administered to both groups of mice via three intragastric intubations of 100 mg
ITR/kg at 4 h intervals on GD 10.5. On GD 18.5, Zn pre-treated mice demonstrated
decreased ITR-mediated growth retardation, cleft palates and postpartum
mortality. A reduction in embryonic MT concentrations was observed in mice
exposed to ITR. Mouse embryos cultured on GD 8.5 with an addition of 15
micromol/L Zn for 48 h had a sixfold greater MT concentration (688 microg/g
protein) than controls. The Zn pretreatment of cultured embryos prevented
malformations and lessened growth retardation caused by 24 h exposure to 17
micromol/L ITR. These results suggest that Zn-mediated induction of MT in mouse
embryos could protect against ITR teratogenicity.
PMID- 9649613
TI - Cytoplasmic ribosomal protein genes of the fission yeast Schizosaccharomyces
pombe display a unique promoter type: a suggestion for nomenclature of
cytoplasmic ribosomal proteins in databases.
AB - We identified 34 new ribosomal protein genes in the Schizosaccharomyces pombe
database at the Sanger Centre coding for 30 different ribosomal proteins. All
contain the Homol D-box in their promoter. We have shown that Homol D is, in this
promoter type, the TATA-analogue. Many promoters contain the Homol E-box, which
serves as a proximal activation sequence. Furthermore, comparative sequence
analysis revealed a ribosomal protein gene encoding a protein which is the
equivalent of the mammalian ribosomal protein L28. The budding yeast
Saccharomyces cerevisiae has no L28 equivalent. Over the past 10 years we have
isolated and characterized nine ribosomal protein (rp) genes from the fission
yeast S.pombe . This endeavor yielded promoters which we have used to investigate
the regulation of rp genes. Since eukaryotic ribosomal proteins are remarkably
conserved and several rp genes of the budding yeast S.cerevisiae were sequenced
in 1985, we probed DNA fragments encoding S.cerevisiae ribosomal proteins with
genomic libraries of S.pombe . The deduced amino acid sequence of the different
isolated rp genes of fission yeast share between 65 and 85% identical amino acids
with their counterparts of budding yeast.
PMID- 9649614
TI - Thermal stability of DNA.
AB - Tij and Delta Hij for stacking of pair i upon j in DNA have been obtained over
the range 0.034-0.114 M Na+from high-resolution melting curves of well-behaved
synthetic tandemly repeating inserts in recombinant pN/MCS plasmids. Results are
consistent with neighbor-pair thermodynamic additivity, where the stability
constant, sij , for different domains of length N depend quantitatively on the
product of stability constants for each individual pair in domains, sijN . Unit
transition enthalpies with average errors less than +/-5%, were determined by
analysis of two-state equilibria associated with the melting of internal domains
and verified from variations of Tij with [Na+]. Enthalpies increase with Tij , in
close agreement with the empirical function: Delta Hij = 52.78@ Tij - 9489, and
in parallel with a smaller increase in Delta Sij . Delta Hij and Delta Sij are in
good agreement with the results of an extensive compilation of published Delta
Hcal and Delta Scal for synthetic and natural DNAs. Neighbor-pair additivity was
also observed for (dA@dT)-tracts at melting temperatures; no evidence could be
detected of the familiar and unusual structural features that characterize tracts
at lower temperatures. The energetic effects of loops were determined from the
melting behavior of repeating inserts installed between (G+C)-rich barrier
domains in the pN/MCS plasmids. A unique set of values for the cooperativity,
loop exponent and stiffness parameters were found applicable to internal domains
of all sizes and sequences. Statistical mechanical curves calculated with values
of Tij([Na+]) , Delta Hij and these loop parameters are in good agreement with
observation.
PMID- 9649615
TI - Comparative structure analysis of vertebrate ribonuclease P RNA.
AB - Ribonuclease P cleaves 5'-precursor sequences from pre-tRNAs. All cellular RNase
P holoenzymes contain homologous RNA elements; the eucaryal RNase P RNA, in
contrast to the bacterial RNA, is catalytically inactive in the absence of the
protein component(s). To understand the function of eucaryal RNase P RNA,
knowledge of its structure is needed. Considerable effort has been devoted to
comparative studies of the structure of this RNA from diverse organisms,
including eucaryotes, primarily fungi, but also a limited set of vertebrates. The
substantial differences in the sequences and structures of the vertebrate RNAs
from those of other organisms have made it difficult to align the vertebrate
sequences, thus limiting comparative studies. To expand our understanding of the
structure of diverse RNase P RNAs, we have isolated by PCR and sequenced 13
partial RNase P RNA genes from 11 additional vertebrate taxa representing most
extant major vertebrate lineages. Based on a recently proposed structure of the
core elements of RNase P RNA, we aligned the sequences and propose a minimum
consensus secondary structure for the vertebrate RNase P RNA.
PMID- 9649616
TI - Localised sequence regions possessing high melting temperatures prevent the
amplification of a DNA mimic in competitive PCR.
AB - The polymerase chain reaction is an immensely powerful technique for
identification and detection purposes. Increasingly, competitive PCR is being
used as the basis for quantification. However, sequence length, melting
temperature and primary sequence have all been shown to influence the efficiency
of amplification in PCR systems and may therefore compromise the required
equivalent co-amplification of target and mimic in competitive PCR. The work
discussed here not only illustrates the need to balance length and melting
temperature when designing a competitive PCR assay, but also emphasises the
importance of careful examination of sequences for GC-rich domains and other
sequences giving rise to stable secondary structures which could reduce the
efficiency of amplification by serving as pause or termination sites. We present
data confirming that under particular circumstances such localised sequence, high
melting temperature regions can act as permanent termination sites, and offer an
explanation for the severity of this effect which results in prevention of
amplification of a DNA mimic in competitive PCR. It is also demonstrated that
when Taq DNA polymerase is used in the presence of betaine or a proof reading
enzyme, the effect may be reduced or eliminated.
PMID- 9649617
TI - BfiI, a restriction endonuclease from Bacillus firmus S8120, which recognizes the
novel non-palindromic sequence 5'-ACTGGG(N)5/4-3'.
AB - A new type IIS restriction endonuclease Bfi I hasbeen partially purified from
Bacillus firmus S8120. Bfi I recognizes the non-palindromic hexanucleotide
sequence 5'-ACTGGG(N)5/4-3' and makes a staggered cut at the fifth base pair
downstream of the recognition sequence on the upper strand, producing a single
base 3' protruding end.
PMID- 9649618
TI - Biophysical and antisense properties of oligodeoxynucleotides containing 7
propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'-deoxyadenosines.
AB - The synthesis of 7-propynyl-, 7-iodo- and 7-cyano-7-deaza-2-amino-2'
deoxyadenosines is described. The nucleosides were synthesized, functionalized
into the phosphoramidites and incorporated into oligodeoxynucleotides.
Spectroscopic melting experiments against complementary RNA showed increases of 3
4 degreesC per modification for single substitutions and smaller increases per
incorporation for multiple substitutions relative to unmodified control
sequences. The 7-propyne and 7-iodo nucleosides were incorporated into antisense
sequences targeting the 3'-UTR of murine C- raf mRNA. Both nucleosides
demonstrated substitution-dependent potency. The sequences with three and four
substitutions of the 7-propyne-7-deaza-2-amino-2'-deoxyadenosine exhibited a 2-3
fold increase in potency over unmodifed controls.
PMID- 9649619
TI - Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with
direct antiviral activity.
AB - Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases
found in secretory granules of human eosinophilic leukocytes. Although the
physiologic function of eosinophils [and thus of the two eosinophil
ribonucleases, ECP and eosinophil-derived neurotoxin (EDN)] remains
controversial, we have recently shown that isolated human eosinophils promote
ribonuclease-dependent toxicity toward extracellular virions of the single
stranded RNA virus, respiratory syncytial virus, group B (RSV-B). We have also
shown that recombinant human EDN (rhEDN) can act alone as a ribonuclease
dependent antiviral agent. In this work, we provide a biochemical
characterization of recombinant human ECP (rhECP) prepared in baculovirus, and
demonstrate that rhECP also promotes ribonuclease-dependent antiviral activity.
The rhECP described here is N-glycosylated, as is native ECP, and has
approximately 100-fold more ribonuclease activity than non-glycosylated rhECP
prepared in bacteria. The enzymatic activity of rhECP was sensitive to inhibition
by placental ribonuclease inhibitor (RI). Although rhECP was not as effective as
rhEDN at reducing viral infectivity (500 nM rhECP reduced infectivity of RSV-B
approximately 6 fold; 500 nM rhEDN, >50 fold), the antiviral activity appears to
be unique to the eosinophil ribonucleases; no reduction in infectivity was
promoted by bovine RNase A, by the amphibian ribonuclease, onconase, nor by the
closely-related human ribonuclease, RNase k6. Interestingly, combinations of
rhEDN and rhECP did not result in either a synergistic or even an additive
antiviral effect. Taken together, these results suggest that that the interaction
between the eosinophil ribonucleases and the extracellular virions of RSV-B may
be specific and saturable.
PMID- 9649620
TI - Novel site-specific DNA modification in Streptomyces: analysis of preferred
intragenic modification sites present in a 5.7 kb amplified DNA sequence.
AB - Both Streptomyces lividans and Streptomyces avermitilis encode similar systems of
post-replicative DNA modification which act site-specifically on closely opposed
guanines on either strand. The modifications can be detected since they react in
vitro with an oxidative derivative of Tris, resulting in strand cleavage.
Previous analysis of the preferred modification site of plasmid pIJ101 indicated
that extensive amounts of flanking sequence, including direct and inverted repeat
structures, are required to direct modification in vivo within a central 6 bp
palindrome. We have now examined the preferred modification sites of a
chromosomal element, the 5.7 kb amplified DNA sequence (ADS5.7) found in certain
S. lividans mutants. In contrast to the pIJ101 site, each of the ADS5. 7sites is
intragenic and modified with a 10-fold reduced frequency. However, similar
extents of flanking sequence are required for authentic double-strand
modification; deletion mutants exhibited different modification profiles,
including displaced double-stranded or single-stranded modi-fication. Comparison
of different modification sites reveals conservation of the central core
sequence, but no significant similarities between flanking sequences. Enhanced
modification was detected in a cloned region of the ADS5.7, suggesting that local
DNA topology, probably influenced by both DNA supercoiling and the nature of
flanking sequences, can influence the modifying activity.
PMID- 9649621
TI - Linear amplicons as precursors of amplified circles in methotrexate-resistant
Leishmania tarentolae.
AB - Gene amplification is frequently observed in Leishmania cells selected for drug
resistance. By gene targeting we have tagged both alleles of the H locus of
Leishmania tarentolae with the neomycin and hygromycin phosphotransferase genes (
neo and hyg ). Selection of these recombinant parasites for low level
methotrexate resistance led to amplification of the H locus as part of linear
amplicons. The availability of tags has permitted us to determine that both
alleles can be amplified in the same cell and that chromosomal deletions are
frequent. When methotrexate concentration was increased in subsequent selection
steps, circles were observed in several mutants. We have introduced a hyg marker
into linear amplicons to test whether the circles originated from linear
amplicons. After selection with a high methotrexate concentration, circles with
the hyg marker were observed, showing that circles can indeed be formed from
linear amplicons. The tagging of H locus alleles permits appreciation of the
extent of genetic rearrangements leading to amplicon formation in Leishmania
cells selected for drug resistance.
PMID- 9649622
TI - Allosteric regulation of a ribozyme activity through ligand-induced
conformational change.
AB - An allosteric ribozyme has been designed using the hammerhead ribozyme as the
active site and aflavin-specific RNA aptamer as a regulatory site. We constructed
six variants with a series of base pairs in the linker region (stem II). Under
single turnover conditions, kinetic studies were carried out in the absence and
presence of flavin mononucleotide (FMN). Interestingly, FMN addition did not
influence the cleavage rate of constructs with a 5-6 bp linker but stimulated the
catalytic activity of those bearing a shorter linker. In particular, the apparent
k cat of Rz3 increases by approximately 10-fold upon addition of saturating
amounts of FMN. To determine the rate constants( K m4and k cat), the ribozyme
regulated most effectively by FMN was further investigated. FMN mainly affected
the k cat value, reflecting the rate limiting conformational change step of the
overall cleavage reaction, depending on helix formation in stem II. Probably, FMN
influences the orientation of structures necessary for the cleavage reaction
through stem II formation. The result of chemical modification revealed that
binding of FMN to the aptamer domain induced the helix formation in stem II
required for catalytic activity. Therefore, a specific FMN-mediated allosteric
interaction seems to promote a conformational alteration from an open to a closed
structure in stem II. The concept of conformational modification in the
allosteric effect is consistent with other allosteric enzymes, suggesting that
such a conformational change is a fundamental feature of allosteric enzymes in
biological systems.
PMID- 9649623
TI - Effects of helical structures formed by the binding arms of DNAzymes and their
substrates on catalytic activity.
AB - As a part of our efforts to clarify structure-function relationships in reactions
catalyzed by deoxyribozymes (DNAzymes), which were recently selected in vitro ,
we synthesized various chimeras and analyzed the kinetics of the corresponding
cleavage reactions. We focused on the binding arms and generated helices composed
of binding arms and substrates that consisted of RNA and RNA, of RNA and DNA or
of DNA and DNA. As expected for the rate limiting chemical cleavage step in
reactions catalyzed by DNAzymes, a linear relationship between log( k cat) and pH
was observed. In all cases examined, introduction of DNA into the binding helix
enhanced the rate of chemical cleavage. Comparison of CD spectra of DNAzyme.
substrate complexes suggested that higher levels of B-form-like helix were
associated with higher rates of cleavage of the substrate within the complex. To
our surprise, the enhancement of catalytic activity that followed introduction of
DNA into the binding helix (enhancement by the presence of more B-form-like
helix) was very similar to that observed in the case of the hammerhead ribozymes
that we had investigated previously. These data, together with other
observations, strongly suggest that the reaction mechanism of metal-ion-dependent
DNAzymes is almost identical to that of hammerhead ribozymes.
PMID- 9649624
TI - Metal ion-dependent hydrolysis of RNA phosphodiester bonds within hairpin loops.
A comparative kinetic study on chimeric ribo/2'-O-methylribo oligonucleotides.
AB - Several chimeric ribo/2'- O -methylribo oligonucleotides were synthesized and
their hydrolytic cleavage studied in the presence of Mg2+, Zn2+, Pb2+and the
1,4,9-triaza-cyclododecane chelate of Zn2+(Zn2+[12]aneN3) to evaluate the
importance of RNA secondary structure as a factor determining the reactivity of
phosphodiester bonds. In all the cases studied, a phosphodiester bond within a 4
7 nt loop was hydrolytically more stable than a similar bond within a linear
single strand, but markedly less stable than that in a double helix. With Zn2+and
Zn2+[12]aneN3, the hydrolytic stability of a phosphodiester bond within a hairpin
loop gradually decreased on increasing the distance from the stem. A similar but
less systematic trend was observed with Pb2+. Zn2+- and Pb2+-promoted cleavage
was observed to be considerably more sensitive to the secondary structure of the
chain than that induced by Zn2+[12]aneN3. This difference in behaviour may be
attributed to bidentate binding of uncomplexed aquo ions to two different
phosphodiester bonds. Mg2+was observed to be catalytically virtually inactive
compared with the other cleaving agents studied.
PMID- 9649626
TI - Automated detection of point mutations using fluorescent sequence trace
subtraction.
AB - The final step in the detection of mutations is to determine the sequence of the
suspected mutant and to compare it with that of the wild-type, and for this
fluorescence-based sequencing instruments are widely used. We describe some
simple algorithms forcomparing sequence traces which, as part of our sequence
assembly and analysis package, are proving useful for the discovery of mutations
and which may also help to identify misplaced readings in sequence assembly
projects. The mutations can be detected automatically by a new program called
TRACE_DIFF and new types of trace display in our program GAP4 greatly simplify
visual checking of the assigned changes. To assess the accuracy of the automatic
mutation detection algorithm we analysed 214 sequence readings from hypermutating
DNA comprising a total of 108 497 bases. After the readings were assembled there
were 1232 base differences, including 392 Ns and 166 alignment characters. Visual
inspection of the traces established that of the 1232 differences, 353 were real
mutations while the rest were due to base calling errors. The TRACE_DIFF
algorithm automatically identified all but 36, with 28 false positives. Further
information about the software can be obtained from http://www.mrc
lmb.cam.ac.uk/pubseq/
PMID- 9649625
TI - Rapid changes of nucleotide excision repair gene expression following UV
irradiation and cisplatin treatment of Dictyostelium discoideum.
AB - Organisms use different mechanisms to detect and repair different types of DNA
damage, and different species vary in their sensitivity to DNA damaging agents.
The cellular slime mold Dictyostelium discoideum has long been recognized for its
unusual resistance to UV and ionizing radiation. We have recently cloned three
nucleotide excision repair (NER) genes from Dictyostelium , the rep B, D and E
genes (the homologs of the human xeroderma pigmentosum group B, D and E genes,
respectively). Each of these genes has a unique pattern of expression during the
multicellular development of this organism. We have now examined the response of
these genes to DNA damage. The rep B and D DNA helicase genes are rapidly and
transiently induced in a dose dependent manner following exposure to both UV
light and the widely used chemotherapeutic agent cisplatin. Interestingly, the
rep E mRNA level is repressed by UV but not by cisplatin, implying unique signal
transduction pathways for recognizing and repairing different types of damage.
Cells from all stages of growth and development display the same pattern of NER
gene expression following exposure to UV-light. These results suggest that the
response to UV is independent of DNA replication, and that all the factors
necessary for rapid transcription of these NER genes are either stable throughout
development, or are continuously synthesized. It is significant that the up
regulation of the rep B and D genes in response to UV and chemical damage has not
been observed to occur in cells from other species. We suggest that this rapid
expression of NER genes is at least in part responsible for the unusual
resistance of Dictyostelium to DNA damage.
PMID- 9649627
TI - Oligonucleotide binding specificities of the hnRNP C protein tetramer.
AB - Through the use of various non-equilibrium RNA binding techniques, the C protein
tetramer of mammalian40S hnRNP particles has been characterized previously as a
poly(U) binding protein with specificity for the pyrimidine-rich sequences that
often precede 3' intron-exon junctions. C protein has also been characterized as
a sequence-independent RNA chaperonin that is distributed along nascent
transcripts through cooperative binding and as a protein ruler that defines the
length of RNA packaged in 40S monoparticles. In this study fluorescence
spectroscopy was used to monitor C protein-oligonucleotide binding in a
competition binding assay under equilibrium conditions. Twenty nucleotide
substrates corresponding to polypyrimidine tracts from IVS1 of the adenovirus-2
major late transcript, the adenovirus-2 oncoprotein E1A 3' splice site, IVS2 of
human alpha-tropomyosin, the consensus polypyrimidine tract for U2AF65, AUUUA
repeats and r(U)20were used as competitors. A 20 nt beta-globin intronic sequence
and a randomly generated oligo were used as competitor controls. These studies
reveal that native C protein possesses no enhanced affinity for uridine-rich
oligonucleotides, but they confirm the enhanced affinity of C protein for an
oligonucleotide identified as a high affinity substrate through selection and
amplification. Evidence that the affinity of C protein for the winner sequence is
due primarily to its unique structure or to a unique context is seen in its
retained substrate affinity when contiguous uridines are replaced with contiguous
guanosines.
PMID- 9649628
TI - hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP
mRNA.
AB - We have previously shown that heterogeneous nuclear ribonucleoprotein C (hnRNP C)
and nucleolin bound specifically to a 29 nt sequence in the 3'-untranslated
region of amyloid precursor protein (APP) mRNA. Upon activation of peripheral
blood mononuclear cells, hnRNP C and nucleolin acquired APP mRNA binding
activity, concurrent with APP mRNA stabilization. These data suggested that the
regulated interaction of hnRNP C and nucleolin with APP mRNA controlled its
stability. Here we have directly examined the role of the cis element and trans
factors in the turnover and translation of APP mRNA in vitro . In a rabbit
reticulocyte lysate (RRL) translation system, a mutant APP mRNA lacking the 29 nt
element was 3-4-fold more stable and synthesized 2-4-fold more APP as wild-type
APP mRNA. Therefore, the 29 nt element functioned as an APP mRNA destabilizer.
RNA gel mobility shift assays with the RRL suggested the presence of endogenous
nucleolin, but failed to show hnRNP C binding activity. However, wild-type APP
mRNA was stabilized and coded for 6-fold more APP when translated in an RRL
system supplemented with exogenous active hnRNP C. Control mRNAs lacking the 29
nt element were unaffected by hnRNP C supplementation. Therefore, occupancy of
the 29 nt element by hnRNP C stabilized APP mRNA and enhanced its translation.
PMID- 9649629
TI - Topological complexity of different populations of pBR322 as visualized by two
dimensional agarose gel electrophoresis.
AB - Neutral/neutral two-dimensional (2D) agarose gelelectrophoresis was used to
investigate populations of the different topological conformations that pBR322
can adopt in vivo in bacterial cells as well as in Xenopus egg extracts. To help
in interpretation and identification of all the different signals, undigested as
well as DNA samples pretreated with DNase I, topoisomerase I and topoisomerase II
were analyzed. The second dimension of the 2D gel system was run with or without
ethidium bromide to account for any possible changes in the migration behavior of
DNA molecules caused by intercalation of this planar agent. Finally, DNA samples
were isolated from a recA-strain of Escherichia coli , as well as after direct
labeling of the replication intermediates in extracts of Xenopus laevis eggs.
Altogether, the results obtained demonstrated that 2D gels can be readily used to
identify most of the complex topological populations that circular molecules can
adopt in vivo in both bacteria and eukaryotic cells.
PMID- 9649630
TI - Pausing of reverse transcriptase on retroviral RNA templates is influenced by
secondary structures both 5' and 3' of the catalytic site.
AB - In the most extensive examination to date of the relationship between the pausing
of reverse transcrip-tase (RT) and RNA secondary structures, pause events were
found to be correlated to inverted repeats both ahead of, and behind the
catalytic site in vitro. In addition pausing events were strongly associated with
polyadenosine sequences and to a lesser degree diadenosines and monoadenosine
residues. Pausing was also inversely proportional to the potential bond strength
between the nascent strand and the template at the point of termination, for both
mono and dinucleotides. A run of five adenosine and four uridine residues caused
most pausing on the HIV-1 template, a region which is the site of much sequence
heterogeneity in HIV-1. We propose that homopolyadenosine tracts can act as
termination signals for RT in the context of inverted repeats as they do for
certain RNA polymerases.
PMID- 9649631
TI - A reliable way of obtaining stable inducible clones.
AB - Inducible gene expression systems provide a powerful tool for the analysis of
gene product functions. The 'Tetracycline (Tc) expression system' has been widely
and successfully used in many instances. However, this system remains somewhat
tedious to use due to: (i) the establishment of a primary cell line
constitutively and stably expressing the Tc-regulated transactivator and (ii) the
obtention of a secondary line expressing the gene of interest in a Tc-dependent
manner. In order to facilitate these two critical steps, we devised an efficient
and molecular biology-free strategy allowing the successful selection of clones
expressing any cDNA under tight regulation.
PMID- 9649632
TI - Enhanced concatemer cloning-a modification to the SAGE (Serial Analysis of Gene
Expression) technique.
AB - The Serial Analysis of Gene Expression (SAGE) method, described in 1995 by
Velculescu et al ., represents a powerful means to compare gene expression
between two mRNA populations. An improvement to SAGE that removes contaminating
linker molecules, which compromise the efficiency of the method, has been
developed. This modification utilises biotinylated PCR primers, which generate
biotinylated linkers at an early stage in the SAGE protocol, thus allowing
removal of the unwanted linkers by binding to streptavidin-coated magnetic beads
at a later stage. The application of this modification resulted in the rapid
generation of high ditag yields and clones with large average insert sizes.
PMID- 9649633
TI - Efficient modification of a human chromosome by telomere-directed truncation in
high homologous recombination-proficient chicken DT40 cells.
AB - Truncation of human chromosomes at desired sites by homologous recombination
techniques enables functional and structural analyses of human chromosomes and
development of human artificial chromosomes. However, this targeted truncation
has been inefficient. We describe here an efficient method for targeted
truncation in the chicken DT40 cells with a high homologous recombination rate.
The human chromosome 22 was transferred into DT40 cells, where human telomeric
repeat (TTAGGG)n was targeted to the LIF locus on the chromosome. Molecular and
cytogenetic analyses showed that the predicted truncation at the LIF locus
occurred in all of the targeted clones.
PMID- 9649634
TI - Chemical mapping of co-existing RNA structures.
AB - In many cases RNA can assume co-existing or meta-stable structures preventing
structure determination by chemical mapping. A novel method is described, by
which RNA is modified with dimethyl sulphate without shifting the distribution of
different structures. The different structures are then separated in native gel
electrophoresis, and structure determination by primer extension can be carried
out separately for each structure.
PMID- 9649635
TI - Solid-phase cDNA library construction, a versatile approach.
AB - A rapid and versatile method for cDNA library construction was developed. It is
based on conventional cDNA library synthesis including all enzymatic steps
usually required, but is performed on a solid support. The cDNA is immobilised
via a biotin residue to streptavidin coupled magnetic beads, which allows rapid
and easy to perform changes of buffers and enzymes. Therefore, it combines speed
(library construction within a single day) with high quality libraries, making it
ideally suited for most purposes.
PMID- 9649636
TI - Dobutamine stress echocardiography for preoperative cardiac risk stratification
in patients undergoing orthotopic liver transplantation.
AB - This study attempts to evaluate the efficacy of dobutamine stress
echocardiography for preoperative cardiac risk stratification in patients
undergoing orthotopic liver transplantation. Two hundred twenty consecutively
submitted patients were evaluated in preparation for orthotopic liver
transplantation. Dobutamine stress echocardiography was performed in 80 patients
with known or suspected coronary artery disease. Follow-up information was
available in 40 patients in the form of cardiac catheterization and/or outcome
from liver transplantation to validate the dobutamine stress echo findings. The
prevalence of coronary artery disease in this cohort was 5% and was closely
associated with the presence of diabetes mellitus. Dobutamine stress
echocardiography, when interpreted as abnormal in the presence of wall motion
abnormalities only, is associated with a sensitivity, specificity, and positive
and negative predictive value of 100%. Dobutamine stress echocardiography is
highly efficacious and should be the screening study of choice to detect coronary
artery disease in patients undergoing orthotopic liver transplantation.
PMID- 9649637
TI - Biliary lipid composition after liver transplantation: effect of allograft
function and cyclosporine.
AB - Biliary lipid composition and bile flow are altered after orthotopic liver
transplantation. Cyclosporine may have additional effects on biliary lipid
composition and secretion. We studied the effects of liver transplantation,
allograft function, and cyclosporine on biliary lipids in humans. Changes in
lipid composition and secretion were correlated with serum cyclosporine levels,
clinical events, and allograft function. Bile samples were withdrawn via a T-tube
at interval time points in 17 patients during the first 3 months
posttransplantation. Total and individual bile acid, cholesterol, and
phospholipid were determined using high-performance liquid chromatography.
Biliary lipid profiles were then correlated with clinical events, serum
cyclosporine levels, and other clinical laboratory values. Biliary lipid
concentrations decreased in 3 patients during periods of graft dysfunction (acute
cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis)
and increased with resolution of the graft injury. Serum cyclosporine levels were
positively correlated with total bile acid, cholesterol, and phospholipid
concentrations in bile. There was no relationship between the composition of
secreted bile acids and serum cyclosporine levels. Bile acid, cholesterol, and
phospholipid secretion were not uncoupled in the presence of cyclosporine. We
concluded that (1) a decrease in biliary lipid concentrations may be an indicator
of worsened graft function in some allografts; (2) biliary lipid concentrations
are correlated with increasing cyclosporine levels; and (3) bile acid composition
is unchanged, and uncoupling of secretion of other biliary lipids is not observed
in the presence of cyclosporine.
PMID- 9649638
TI - Risk factors for recurrence of hepatitis C after liver transplantation.
AB - Recurrent hepatitis C is a frequent complication after liver transplantation for
hepatitis C virus-related cirrhosis, but risk factors related to its development
remain ill defined. Twenty-three patients receiving a primary liver graft for
hepatitis C virus-related cirrhosis and with an assessable biopsy performed at
least 6 months after liver transplantation were studied retrospectively. The end
point of this study was to look for risk factors associated with the development
of histologic hepatitis C in the graft. Thirty-six major variables were studied,
and those reaching significance by univariate analysis were included in a
multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis
C. On univariate analysis, six variables showed significant predictive value:
increased immunosuppression for treatment of acute rejection; pretransplant
hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months
after transplantation; and mean blood trough levels of cyclosporine in the first
6 months posttransplantation. On multivariate analysis, two variables retained
independent statistical significance as predictors of hepatitis C recurrence,
namely receipt of antirejection therapy (P = .0087) and lower mean cyclosporine
levels in the first 6 months after transplantation (P = .0134). Therefore,
recurrence of hepatitis C after liver transplantation seems to be at least
partially related to posttransplantation immunosuppressive therapy.
PMID- 9649639
TI - An appraisal of percutaneous treatment of liver metastases.
AB - Percutaneous treatments, such as ethanol injection and radiofrequency, have been
recently proposed for the treatment of liver metastases. The aim of this study
was to evaluate the effects of these treatments in a series of 8 patients who
subsequently underwent liver resection. These patients had been treated with
percutaneous methods between December 1995 and May 1997. In 6 patients, the
primary tumor was colonic; in 2 patients, carcinoid; and in 1 patient, ileal
leiomyosarcoma. The lesions were all initially small in size (1.5 to 3.5 cm),
single in 7 patients, and multiple in 1 patient with a carcinoid tumor. The
initial decision for percutaneous treatment had been made on subjective grounds
by the radiologists who originally saw the patients. The number of percutaneous
treatment sessions ranged from 2 to 21. In all patients, a progression of the
disease occurred. Four patients underwent a right hepatectomy; 1 patient, a left
lobectomy; 2 patients, a segmentectomy; and 1 patient, a wedge resection. There
was no operative mortality in any of these 8 patients. Two patients presented
with seeding of the neoplasm on the diaphragm, which was resected. Histologic
examination of all surgical specimens revealed the presence of vital neoplastic
tissue; only two specimens of carcinoid tumors showed more than 50% necrosis of
the nodules treated percutaneously. These results led us to express doubts as to
the efficacy of percutaneous ablative treatment for liver metastases.
PMID- 9649640
TI - A prospective, randomized, double-blind trial evaluating the efficacy of
ursodeoxycholic acid in prevention of liver transplant rejection.
AB - Acute cellular rejection (ACR) after orthotopic liver transplantation occurs in
50% to 80% of patients despite the recent advances in immunosuppressive therapy.
Adjuvant use of ursodeoxycholic acid (UDCA) is theoretically attractive, but
studies have shown conflicting results. In this randomized, controlled study, we
evaluated the efficacy of UDCA in reduction of the incidence of ACR. Thirty
patients were randomized to receive either UDCA (15 mg/kg) or placebo in addition
to the standard triple-drug regimen; 14 patients received UDCA, and the rest
received placebo, for 3 to 6 months. The diagnosis of ACR was based on histologic
criteria. Three patients withdrew from the study within 1 month of therapy, all
because of capsule size. There was no difference in the total incidence of ACR
between the placebo and UDCA groups, with 12 and 11 episodes within 6 months,
respectively; the overall incidence of rejection was 77%. There were also no
differences in the incidence of recurrent rejection, in the number of rejection
episodes occurring after 5 days of therapy, or in the use of OKT3. There was no
difference in 1-year survival between groups. This study shows that adjuvant
therapy with UDCA in addition to standard triple-drug immunosuppressive therapy
does not reduce the incidence of ACR.
PMID- 9649641
TI - The effect of a positive T-lymphocytotoxic crossmatch on hepatic allograft
survival and rejection.
AB - The influence of crossmatching in liver transplantation is still controversial,
and at present, our unit does not alter management according to the result of
standard lymphocytotoxicity testing. This study retrospectively assessed outcome
of grafts transplanted in the presence of preformed antidonor cytotoxic antibody.
One hundred twelve patients undergoing their first orthotopic liver
transplantation had results available (mean follow-up: 18 months). Twelve
patients had a positive crossmatch and 100 negative. The 1-year graft survival
was 58% in the positive crossmatch group, compared with 81% in the negative
crossmatch group (P = .02). The 1-year patient survival was 83% in the positive
crossmatch group compared with 90% in the negative group (P = .41). Acute
cellular rejection occurred in 6 of 7 (86%) grafts surviving more than 7 days in
the positive crossmatch group compared with 46 of 88 (52%) grafts in the negative
group (P = .09). However, episodes of further acute cellular rejection requiring
treatment occurred in 4 of the 6 grafts in the positive crossmatch group but in
only 4 of the 46 grafts with a negative crossmatch (P = .0006). The authors
conclude that evidence exists in our population that preformed antidonor
antibodies adversely affect the outcome of hepatic allografts but not patient
survival.
PMID- 9649642
TI - Weight change and obesity after liver transplantation: incidence and risk
factors.
AB - Obesity is a concern in the long-term management of patients following liver
transplantation, yet the risk of obesity and the factors that influence its
development have not been well defined. We evaluated posttransplantation weight
change among a cohort of 774 adults who had their height and weight recorded
before liver transplantation at three major centers. Obesity was defined as a
body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was
adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2
pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1
kg/m2 in the second year, and very little with subsequent observation. Among 320
patients who were not obese before transplantation, 21.6% became obese within 2
years after transplantation. On evaluation of numerous potential donor and
pretransplantation risk factors, greater recipient BMI, greater donor BMI, and
being married were found to be predictors of subsequent obesity (P < .05).
Posttransplantation predictors of obesity included absence of acute cellular
rejection, higher cumulative prednisone dose in the second year, and cyclosporine
based immunosuppression, although only rejection and prednisone dose remained
predictors on multivariate analysis. Despite the marked weight gain after
transplantation, prevalence of obesity at 2 years was only slightly greater than
in the general US population. Obesity occurred commonly after liver
transplantation, sometimes with a striking gain in weight. In addition to BMI at
transplantation, donor BMI, marital status, occurrence of acute rejection, and
prednisone dose affected the incidence of obesity.
PMID- 9649643
TI - Intraoperative donor cholangiography.
AB - Biliary drainage has long been called the Achilles' heel of liver
transplantation, and biliary complications compromise the success of liver
transplantation by increasing graft loss and the rates of a required second
operation, morbidity, and mortality. One cause of complications is unrecognized
anomalous biliary anatomy. We examined 73 intraoperative donor duct
cholangiograms (IODDCs) to assess our ability to identify biliary anomalies
intraoperatively. Normal anatomy was seen in 42% (31/73); some part of the right
sided biliary system drained into the left bile duct in 22% (16/73); trifurcated
systems with a single branch point for the right posterior, right anterior, and
left ducts appeared in 16% (12/73); low insertion of a right segmental duct to
the hepatic duct was seen in 11% (8/73); and drainage of a right segmental duct
into the cystic duct or into the hepatic duct at the cystic duct origin was noted
in 8% (6/73). It was believed that the last group represented a condition that
dictated extra caution in biliary reconstruction. The incidence of radiographic
recognition of these anomalies was more than twice the clinical recognition in
our patient population, implying that many such "problem" ducts usually go
unrecognized. IODDCs facilitate training of transplant fellows. Costs are low,
and morbidity is nil.
PMID- 9649644
TI - Splanchnic hyperemia after liver transplantation in patients with end-stage liver
disease.
AB - Systemic and splanchnic hemodynamic parameters were evaluated in 12 patients with
cirrhosis before and 3 and 6 months after liver transplantation. Results were
compared with those obtained in 8 healthy subjects. Three months after liver
transplantation recipients had an increase in mean arterial pressure (98 +/- 7 v
78 +/- 9 mmHg; P < .05), an insignificant decrease in cardiac index (3. 4 +/- 0.6
v 4.0 +/- 1.0 L . min-1 . m-2), and a marked increase in peripheral vascular
resistance (1,563 +/- 308 v 800 +/- 205 dyne . s . cm-5; P < .05) compared with
pretransplantation values. Portal blood flow was also significantly increased
(1,494 +/- 200 v 829 +/- 130 mL/min; P < .05). These hemodynamic changes were
more pronounced 6 months after transplantation (mean arterial pressure, 100 +/- 8
mmHg; cardiac index, 3.0 +/- 1.0 L . min-1 . m-2; P < .01; peripheral vascular
resistance, 1,680 +/- 405 dyne . s . cm-5; portal blood flow, 1,520 +/- 180
mL/min). Systemic hemodynamics 6 months after liver transplantation were similar
to those observed in the healthy control group (mean arterial pressure, 95 +/- 6
mmHg; cardiac index, 2.9 +/- 0.9 L . min-1 . m-2; peripheral vascular resistance,
1,480 +/- 380 dyne . s . cm-5). However, portal blood flow was still
significantly higher than in healthy controls at 6 months (1,520 +/- 180 v 910 +/
140 mL/min; P < .05). This study shows that systemic hemodynamics are normalized
after liver transplantation. However, an increase in portal blood flow occurs and
persists for at least 6 months after liver transplantation. Further studies are
needed to clarify the cause of the abnormally high portal flows.
PMID- 9649645
TI - Cholestatic hepatitis C in liver allografts.
AB - Some liver allograft recipients with hepatitis C virus (HCV) infection develop
hyperbilirubinemia, which might be the result of a cholestatic variant of
hepatitis C. We evaluated all liver biopsy samples from 6 liver transplant
recipients who had polymerase chain reaction-positive HCV infection and
histologic evidence of hepatitis and jaundice and compared them with liver biopsy
samples from a control group of transplant recipients with HCV hepatitis without
jaundice. Patients with known ductopenic rejection, biliary obstruction, or co
infection with hepatitis A or B were excluded from the study. Measurement of
viral titers and genomic typing were performed when possible. Six patients
developed hepatitis and jaundice, with maximum bilirubin levels ranging from 5.8
to 47.6 mg/dL. In this group, 5 (83%) had moderate interface hepatitis (control
group, 15%), 6 (100%) had confluent necrosis (control group, 12%), 5 (83%) had
bridging fibrosis (control group, 18%), 4 (67%) had significant hepatocyte
swelling (control group, 9%), 4 (67%) had prominent ductular proliferation
(control group, 3%), and 6 (100%) had mild duct damage and inflammation (control
group, 53%). All 6 of the patients with cholestasis had allograft failure. Of
these, three allografts were available for review, which did not reveal occult
obstruction, rejection, or duct loss. All patients in the control group have
retained their allografts. In 4 patients with cholestasis, the median HCV RNA
titer was 93.97 mEq/mL, with a mean of 54.19 mEq/mL (control mean = 5.2 mEq/mL).
Five patients also underwent viral genomic typing: 2 with type 1a, 2 with type
1b, and 1 with mixed type 1a and 1b. Cholestasis in patients with
posttransplantation hepatitis C may be caused by an aggressive HCV infection that
exhibits histologic features of confluent necrosis, hepatocyte swelling, and/or
ductular proliferation. Viral titers are often increased in such patients.
PMID- 9649646
TI - Bone metabolism in orthotopic liver transplantation: a prospective study.
AB - Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients
with end-stage liver disease who were evaluated for orthotopic liver
transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26
patients who underwent OLT. Serum and urinary electrolyte and mineral levels,
serum liver function test results, and parathyroid hormone (PTH), osteocalcin
(BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD
of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT.
At baseline, 40.7% of patients had BMD below the fracture threshold (0.800
g/cm2). Using multiple stepwise regression analysis, we found that BMD was
significantly (P < .0001) affected by age, serum creatinine level, and PTH level
but not by indices of cholestasis or liver function. In the patients who
underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after
OLT. Thereafter, BMD returned to pretransplant values. A significant increase in
serum BGP was observed after 6 (P < .02) and 12 (P < . 005) months. PTH levels
increased progressively 3 (P < .02), 6 (P < . 001), and 12 (P < .0001) months
after OLT. This increase did not seem to be caused by cyclosporine-induced
nephropathy. It was concluded that osteopenia is a major complication in hepatic
cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12
months after OLT indicates metabolic activation of osteoblasts. The increase in
PTH levels after OLT warrants further investigation.
PMID- 9649647
TI - Recurrent hepatitis C virus infection after liver transplantation:
immunohistochemical assessment of the viral antigen.
AB - BACKGROUND: The value of immunohistochemical methods to identify hepatitis C
virus antigen (HCVAg) in liver tissue has not been established. We have evaluated
the significance of HCVAg expression in livers of patients with transplants and
recurrent hepatitis C virus (HCV) infection. METHODS: Forty-two liver biopsy
specimens from 32 liver-transplant recipients with recurrent HCV infection were
tested for HCVAg using fluorescein isothiocyanate-labeled polyclonal,
polyreactive human immunoglobulin. Histologic assessment of liver and
quantitation of HCV RNA in sera were carried out in specimens obtained
simultaneously with biopsies. RESULTS: HCVAg was found in 33% of the liver
specimens obtained during the first month after transplantation and in all liver
specimens obtained between 1 and 18 months after transplantation. Amounts of the
antigen were significantly greater in specimens obtained more than 1 month after
transplantation. A statistically significant increase of the average HCV RNA
level in serum was observed in samples tested after the first month after the
transplantation, and some decrease in the HCV RNA level was found in those
obtained between 6 and 18 months after transplantation. Larger amounts of HCVAg
were observed in specimens corresponding to episodes of acute or chronic
hepatitis than in those associated with minimal parenchymal evidence of
rejection. CONCLUSIONS: OBSERVATIONS of HCVAg expression in liver biopsy
specimens indicated that the presence of viral antigens in hepatocytes is a
constant finding in specimens obtained 1 month or longer after transplantation.
Although large amounts of HCVAg correlated with acute or chronic hepatitis, the
nature of this association with the development of pathologic changes remains to
be established.
PMID- 9649648
TI - Late hypertension after liver transplantation: a comparison of cyclosporine and
tacrolimus (FK 506).
AB - Hypertension frequently develops early after liver transplantation when
cyclosporine-based immunosuppression is used. However, initial experience with
tacrolimus has suggested that its use leads to a lower early incidence of
hypertension. In this study, the blood pressure status of patients treated with
cyclosporine (n = 131) and those treated with tacrolimus (n = 28) was compared 24
months after liver transplantation. At this time interval, the prevalence of
hypertension in the cyclosporine and tacrolimus groups were 82% and 64%,
respectively (P < .05). For those patients who were hypertensive by 24 months,
onset was delayed in the tacrolimus group compared with the cyclosporine group:
40% versus 71% and 73% versus 93% at 1 and 12 months, respectively (P < .05).
Within the cyclosporine group, patients with hypertension were heavier than those
with normal blood pressure, 84.7 +/- 1.8 versus 73.4 +/- 4.0 kg, respectively (P
< .05). Within the tacrolimus group, hypertensive patients had lower glomerular
filtration rates and higher renal vascular resistances compared with normotensive
patients, 74 +/- 12 versus 47 +/- 6 mL/min and 15,711 +/- 2,445 versus 28,830 +/-
4,310 dyne/s/cm5/m2, respectively (P < .05). There were no within-group
differences for age, gender, pretransplant history of hypertension, family
history of hypertension, graft function, or daily doses of prednisone,
cyclosporine, or tacrolimus. These results indicate that, compared with
cyclosporine, the onset of hypertension after liver transplantation is delayed
and less prevalent with tacrolimus. Additionally, hypertension is associated with
increased body weight in cyclosporine-treated patients and with more severe renal
dysfunction in patients receiving tacrolimus. The relationships of these findings
to the development of posttransplant hypertension requires further study.
PMID- 9649649
TI - Tolerance induction using bone marrow transplantation.
PMID- 9649650
TI - Stress echocardiography identifies coronary artery disease in liver transplant
candidates.
PMID- 9649651
TI - Announcements
AB - Copyright
PMID- 9649652
TI - Schnitzler's syndrome versus adult onset Still's disease.
AB - We report the case of a 50-year-old man with a 4-year history of high spiking
fever accompanied by a widespread, urticarial, non-pruritic or only sometimes
mildly pruritic eruption and arthralgia. He also had generalized lymphadenopathy,
hepatosplenomegaly, and hyperosteoses of the lower lumbar spine. Laboratory
examination revealed an elevated erythrocyte sedimentation rate, elevated white
blood cell and platelet counts, hypoalbuminemia, and elevated serum IgM with IgM
kappa monoclonal immunoglobulin. We diagnosed his condition as Schnitzler's
syndrome, in contrast to the diagnosis of adult onset Still's disease, for which
he had been initially followed up by his internist. We compare clinical and
histopathological findings for both diseases and, as this patient meets two of
the six existing diagnostic criteria for adult onset Still's disease, we propose
that Schnitzler's syndrome is an important entity to be added to the list of
differential diagnoses for adult onset Still's disease.
PMID- 9649653
TI - Pemphigus vulgaris on an old surgical scar: Koebner's phenomenon?
AB - Pemphigus is an autoimmune bullous skin disorder. Several cases have been
reported to originate in traumatized areas or on a scar, suggesting Koebner's
phenomenon. Pemphigus can either remain localized or subsequently extend. This
paper reports on a 60-year-old man in whom pemphigus vulgaris began on a 40-year
old surgical scar. The pemphigus initially remained localized to the scar and
subsequently extended after two months. The time to onset of this bullous disease
on the scar was especially long, compared to that which has been previously
reported in the literature. A few cases have been reported where pemphigus
developed a few months to a few years after surgery. A time to onset exceeding 3
years is extremely rare.
PMID- 9649654
TI - The use of skin substrates deficient in basement membrane molecules for the
diagnosis of subepidermal autoimmune bullous disease.
AB - A case is presented of subepidermal, autoimmune bullous disease in which the
initial examinations suggested the combination of epidermolysis bullosa acquisita
and bullous pemphigoid. The diagnosis of epidermolysis bullosa acquisita was made
by indirect immunofluorescence microscopy: the patient's serum bound to normal
skin substrate but not to type VII collagen-deficient skin substrate derived from
a patient with mutilating dystrophic epidermolysis bullosa. The use of skin
substrates deficient in basement membrane molecules also excluded the presence of
concomitant, circulating bullous pemphigoid autoantibodies in our patient. The
diagnosis of epidermolysis bullosa acquisita was confirmed by split mapping,
fluorescence overlay antigen mapping and Western blot.
PMID- 9649655
TI - Linear IgA disease and ulcerative colitis.
AB - Linear IgA disease is an acquired bullous disease of the skin characterized by
linear IgA deposits along the dermal-epidermal junction. Inflammatory bowel
diseases have been rarely reported in association with linear IgA disease. We
have recently observed a patient suffering from ulcerative colitis who developed
a cutaneous bullous eruption that was diagnosed as a linear IgA disease. Foreign
antigens penetrating the inflamed bowel mucosa might give rise to the production
of autoantibodies cross-reacting with the cutaneous antigens involved in the
pathogenesis of linear IgA disease.
PMID- 9649656
TI - Crohn's disease masquerading as aphthous ulcers.
AB - Although intraoral involvement in Crohn's disease (CD) is observed in only
approximately 9% of cases, oral inflammation precedes intestinal symptoms of CD
in about 60% of these patients. We describe a 20-year-old male with recurrent,
painful, intraoral lesions who presented no other signs of systemic disease apart
from severe loss of body weight. From the routinely screened serological
parameters only the erythrocyte sedimentation rate and the acute phase reactants
were elevated. A biopsy from the vestibular mucosa revealed a dense mononuclear
infiltrate and, focally, small noncaseating granulomas suggestive of CD.
Gastrointestinal endoscopy was performed showing mucosal involvement reaching
from the esophagus to the descending colon. The diagnosis of active CD was
confirmed by histopathology of intestinal biopsy specimens. As oral lesions are
sometimes treated without a definite diagnosis, we emphasize the need to search
for underlying systemic illness in the differential diagnosis of recurrent
inflammatory lesions of the oral cavity.
PMID- 9649657
TI - Production of host-protective (IFN-gamma), host-impairing (IL-10, IL-13) and
inflammatory (TNF-alpha) cytokines by PBMC from leprosy patients stimulated with
mycobacterial antigens.
AB - The production of IFNgamma, IL-10, IL-13 and TNFalpha was determined using PBMC
from 7 tuberculoid (TT) and 7 lepromatous leprosy (LL) patients, after
stimulation with several mycobacterial antigens, in an attempt to characterize
the cytokine responses to these antigens. The results showed that TT patients
displayed higher IFNgamma levels than LL patients with the mycobacterial antigens
tested, but no differences in IL-10 production were observed between the two
groups. MLSC antigen was associated with the lowest IFNgamma production in TT and
LL groups. Only BCG could be identified with stimulation of IFNgamma production
in some LL patients. The mycobacterial antigens SP+, SP- and BCG were associated
with higher TNFalpha production in patients and controls, suggesting that these
antigens could be involved in immunopathological effects. Our findings showed
that the antigens tested were associated with a heterogeneous cytokine production
in leprosy patients. Further studies are required to establish if an individual
antigen can be identified as inducing a protective immune response in leprosy.
PMID- 9649658
TI - Drug eruption due to Bufferin showing erythema exsudativum multiforme with a
photo-recall-like phenomenon.
AB - A 21-year-old woman who had been taking several kinds of analgesics to treat
dysmenorrhea developed episodic attacks of a purpuric macular eruption and a
burning sensation on unexposed areas of the upper chest and back where she had
sustained severe sunburn eight months earlier. Target-like lesions developed on
these areas after intake of Bufferin, a combination of aspirin and dialuminate.
After the eruptions had abated following systemic administration of a
corticosteroid agent, a challenge test was performed, using a quarter of a tablet
of Bufferin. The patient developed a temporary burning sensation and a
erythematous color on the previously sunburned skin. We diagnosed this case as a
drug eruption due to Bufferin showing erythema exsudativium multiforme with a
photo-recall-like phenomenon. In our case, skin tests would be useful to confirm
the causal drug.
PMID- 9649659
TI - Expression of cathepsins in dermal fibrous tumors: an immunohistochemical study.
AB - Cathepsins are lysosomal proteases that are distributed in many normal tissues
and are primarily responsible for intracellular catabolism and turnover. The
increased level of cathepsins in tumors together with their ability to degrade
extracellular matrix proteins has led to the hypothesis that they are involved in
the process of invasion and metastasis. We studied immunohistochemically the
expression of cathepsins B, pro-D and pro-L in 8 cases of dermatofibrosarcoma
protuberans (DFS), five cases of atypical fibroxanthoma (AFX) and twenty cases of
dermatofibroma (DF). Expression of cathepsins B and pro-D could be detected in 5
of the 8 cases (62.5%) of DFS, whereas cathepsin pro-L was found in 4 (50%)
cases. All AFX expressed cathepsin pro-L, whereas cathepsins B and pro-D were
observed in 4 out of 5 cases. None of the malignant tumors showed a recurrence or
metastasis after a period of four years. We found no expression of cathepsins in
DF. In the epidermis and appendages, an expression of cathepsins pro-D, pro-L and
B was seen. We conclude that cathepsins may be markers of increased metabolism
rather than specific markers of malignancy.
PMID- 9649660
TI - A comparison of the efficacy and safety of lymecycline and minocycline in
patients with moderately severe acne vulgaris.
AB - A multicentre, randomised, double-blind and double-dummy study was conducted to
compare the efficacy and safety of lymecycline (n = 71) with that of minocycline
(n = 73) in 144 patients with moderately severe acne vulgaris. Patients with an
acne score of 1-5 on the Leeds scale received oral lymecycline, 300 mg/day for 2
weeks, then 150 mg/day for 10 weeks or oral minocycline, 100 mg/day for 2 weeks
then 100 mg every other day for 10 weeks. Inflammatory, non-inflammatory and
total lesion counts were determined at baseline (week 0) and after 4, 8 and 12
weeks' treatment, and global efficacy and safety assessments were made by the
patient and investigator at the end of the study. Both treatments were equally
effective at reducing differential lesion counts and improving acne condition and
severity, with no significant differences between treatments. Inflammatory
lesions were reduced by 50.6% and 52.2% with lymecycline and minocycline,
respectively, and non-inflammatory lesions by 40.6% and 32.2%. Acne severity was
reduced by 42.4% with lymecycline and by 47.9% with minocycline. A total of 4.3%
of lymecycline recipients and 4.1% of minocycline recipients experienced
treatment-related adverse events, the majority of which were mild in nature.
Lymecycline was as effective as minocycline for the treatment of moderately
severe acne vulgaris. Both treatments were well tolerated, although there were
slightly fewer adverse gastrointestinal and dermatological effects with
lymecycline.
PMID- 9649661
TI - Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on inflammatory responses in
psoriasis.
AB - Topical application of 1alpha,25-dihydroxyvitamin D3 (VD3) is thought to be
beneficial in psoriasis because of its action in regulating keratinocyte
proliferation and inflammation mediated by various cytokines. We assessed the
effect of VD3 on the production levels of interferon (IFN)-alpha, interleukin
(IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in mitogen-stimulated
peripheral blood mononuclear cells (PBMC) of psoriatic patients. The results
demonstrated that VD3 significantly inhibited IFN- , IL-6, and IL-8 levels
produced by concanavalin A (Con A)-stimulated PBMC of psoriatic patients in a
dose-dependent manner, and reduced mRNA expression for IFN- and IL-8. These
findings suggest that in addition to the direct anti-proliferation effect on
keratinocytes, VD3 may down-regulate the inflammatory cytokine production by
infiltrating cells in psoriatic lesions.
PMID- 9649662
TI - Multiple squamous cell carcinomas of the skin during long-term treatment with
hydroxyurea.
AB - Hydroxyurea is a chemotherapeutic agent used extensively for myeloproliferative
disorders. Cutaneous side effects have been described during long-term
hydroxyurea treatment. We described the occurrence of multiple squamous cell skin
carcinomas in a patient treated with hydroxyurea for chronic myelogenous
leukemia. The lesions were removed and the hematological therapy switched to
busulfan. In a previously reported case, the development of cutaneous epithelial
cancers required the discontinuation of hydroxyurea, in addition to the surgical
excision of the neoplastic lesions. Since squamous cell carcinoma is a malignant
cutaneous neoplasm that can metastatize, the surveillance of skin changes is
advisable during hydroxyurea treatment.
PMID- 9649663
TI - Is chronic ulcerative stomatitis an entity? Clinical and immunological findings
in 18 cases.
AB - Chronic ulcerative stomatitis (CUS), a rare disease of oral mucosa found to be
associated with unusual antinuclear antibodies reactive exclusively with squamous
epithelia (squamous epithelium-specific antinuclear antibodies - SES-ANA), has
been reported to occur almost exclusively in older females and to respond
dramatically to antimalarials. We report on a large series of 18 cases positive
for SES-ANA, 15 of them with active CUS, followed-up for several years. We found
that the disease may occur, although rarely, in men and younger females. The
antibodies persist after clearance of mucosal lesions, are fixed in vivo and also
in uninvolved skin and other mucosa, and may occur in patients without CUS. Thus
their pathogenic potential remains to be established. We also describe some
unusual cases of CUS, one associated with cicatricial conjunctivitis, another
associated with gluten-sensitive enteropathy and bizarre skin lesions, and 3
cases associated with lichen planus (LP) or LP-like lesions. The antimalarials,
initially highly effective, even for several months or years, not infrequently
proved to be insufficient and the relapses responded usually only to combined
therapy with chloroquine and small doses of corticosteroids. SES-ANA antibodies
are quite specific and present an immunologic marker of this unusual autoimmune
disease.
PMID- 9649664
TI - Sweet's syndrome associated with cutaneous T cell lymphoma.
AB - Although the association of Sweet's syndrome with haemoproliferative disorders or
solid malignant tumors is well known, only two previous observations associated
with T lymphoma have been reported. We report the first observation of Sweet's
syndrome associated with cutaneous T cell lymphoma. The role of a cytokine
cascade released by an abnormal T cell clone is discussed as an initiating event
responsible for secondary infiltration with neutrophils.
PMID- 9649665
TI - Behcet's disease-like symptoms induced by the Herpes simplex virus in ICR mice.
AB - Herpes simplex virus (HSV) infection has been suggested to be one of the
etiologic or triggering factors in Behcet's disease. To test this hypothesis, 258
ICR mice were inoculated with HSV type 1 (KOS strain). After the induced
infection, 86 mice (33.3%) died, 77 (29. 8%) showed Behcet's disease-like
symptoms, and 95 (36.8%) had a healthy, normal appearance or just a single
symptom. The symptoms included skin ulcers on the earlobe, neck, abdomen, back or
face (57. 1%); eye syndromes (39.0%); partial hair loss (33.8%); genital ulcers
(19.5%); bullae (11.7%); arthritis (5.2%); gastrointestinal ulcer (5.2%); and
tongue ulcers (3.9%). The induced Behcet's disease-like symptoms are similar to
the clinical manifestations of ulcers, uveitis, and arthritis which have been
significant in diagnosing Behcet's disease in patients.
PMID- 9649666
TI - Recurring atypical ("pseudosarcomatous") cutaneous fibrous histiocytoma.
AB - Atypical ("pseudosarcomatous"), cutaneous, fibrous histiocytoma is a rare
connective tissue tumor arising on the trunk and limbs in young adults. Its
histological diagnosis is difficult. We report the case of a 25-year-old woman
who presented a nodule on her left leg. Two years after an incomplete excision,
she developed a large local recurrence. Additional radiotherapy, after total
reexcision was performed. This treatment was successful and no further recurrence
occurred. Clinicopathological features of atypical ("pseudosarcomatous"),
cutaneous, fibrous histiocytoma are reviewed. Differential diagnoses, including
atypical fibroxanthoma, angiomatoid fibrous malignant histiocytoma and aneurysmal
fibrous histiocytoma are discussed.
PMID- 9649667
TI - Introduction to the round table: "UV and the immune system"
PMID- 9649668
TI - Immunosuppression induced by chronic ultraviolet irradiation in humans and its
prevention by sunscreens.
PMID- 9649669
TI - Successful treatment of Grover's disease with calcipotriol.
AB - We report the case of an 84-year-old man with clinical, histological and electron
microscopic features of a Darier-like pattern of Grover's disease. The lesions
had a persistent course, with a 5-month history before diagnosis and a clinical
onset 2 years after the surgical removal of a cholangiocarcinoma. A significant
clinical improvement was observed after a three-week course of calcipotriol
ointment applied as a monotherapy regimen. Clinical uses of topical calcipotriol
in dermatological conditions are reviewed with emphasis on dyskeratotic
disorders.
PMID- 9649671
TI - Surgery and cyclosporine A in the treatment of erosive lichen planus of the feet.
AB - Erosive lichen planus is known to be relatively unresponsive to medical
treatment. Surgery could be an alternative treatment for this disease. We report
the case of a 68-year-old man with a 10-year history of painful, disabling,
ulcerative lesions on the soles of both feet. All previous topical and oral
treatments had failed and his condition was gradually worsening. Cyclosporine A
was administered twice. The first time, systemic cyclosporine A gave a marked but
only temporary improvement. The second time, treatment with cyclosporine A was
begun 10 days before the ulcer on his left sole was covered with a Thiersch split
skin graft. The grafting was successful, so cyclosporine A was gradually reduced
to smaller maintenance doses and 10 months later it was completely withdrawn. The
patient refused to undergo surgery on his right foot thus providing the
opportunity to compare the results. At the present time, eighteen months
following grafting and ten months after total withdrawal of cyclosporine A, the
condition of the left sole is stable and free from pain while the ungrafted ulcer
on his right sole is still painful and has increased in size.
PMID- 9649670
TI - Verrucous cyst.
AB - A verrucous cyst is an unusual, histopathologically distinctive, epidermoid cyst
characterised by verrucous changes in its wall. We report two cases of verrucous
cysts in different patients, one on the back and the other on the cheek.
Clinically, the lesions were thought to represent an epidermoid cyst and a basal
cell carcinoma, respectively. Histologically, we found in both cases an
intradermal epidermoid cyst lined by a stratified squamous epithelium with focal
cytopathogenic viral changes, consisting of papillomatosis, ortho- and
parakeratosis, and hypergranulosis. One case also showed, within the squamous
areas of the hyperplastic epithelium, occasional squamous eddies. These
histopathological features support the diagnosis of verrucous cyst, which may
represent a manifestation of human papillomavirus infection. This virus may
induce cyst formation or just infect a pre-existing one.
PMID- 9649672
TI - Dose-responses for UV-induced suppression of various immune responses.
PMID- 9649673
TI - Rheumatoid vasculitis in a patient with seronegative rheumatoid arthritis.
AB - We report on a 47-year-old woman with a 10-year history of seronegative
rheumatoid arthritis (RA) who had experienced an episode of bilateral aseptic
pleuritis, and in whom livedo reticularis and ulcers had developed on both lower
extremities. Histological examination revealed rheumatoid vasculitis. In
rheumatoid vasculitis, high titers of rheumatoid factors are commonly observed.
In our case, however, there have been no characteristic laboratory findings
throughout the course of the disease so far, despite the active RA. This report
describes a rare case of seronegative RA with systemic rheumatoid vasculitis.
PMID- 9649674
TI - Epidemiology of contact dermatitis. The information network of departments of
dermatology (IVDK) in Germany.
AB - In 1988, the multicenter project "Information Network of Departments of
Dermatology (IVDK)", including eight university skin hospitals was founded. It
now comprises 30 participating centers. At these centers, all patch test results
are recorded, together with important anamnestic details and, twice a year, these
are sent to the data center at the Gottingen University Skin Hospital. Regular,
descriptive analyses of data collected by this epidemiological surveillance
system serve the different purposes discussed in this paper: 1) observation of
"sentinel events"; e.g. an increase in the proportion of patients tested who were
sensitized to a certain allergen, or the identification of certain subgroups at
particular risk as a starting point for further research or preventive action,
and 2) advancement of good clinical practice in patch testing. In October 1996, a
working group of the European Society of Contact Dermatitis (ESCD) called the
"European Surveillance System on Contact Allergies (ESSCA)" was established with
a similar aim of communal data collection and analysis.
PMID- 9649675
TI - Transient leucoderma appearing in an untreated area following contact
immunotherapy for alopecia areata.
AB - One of the possible unwanted side effects following contact immunotherapy of
alopecia areata is skin hypopigmentation, either in the form of a transient, post
inflammatory hypopigmentation or as the development of a persistent, depigmented
patch. A case of leucoderma occurring on the forehead of a 16-year-old girl
following application of squaric acid dibutylester to the scalp for the treatment
of alopecia areata is described. Past medical and family history were negative
for vitiligo and autoimmune disorders. The hypopigmented patch was distant from
the scalp area where squaric acid dibutylester had been applied, and it was not
preceded by any sign of eczema, erythema or itch in the same area. Moreover, it
faded as soon as treatment was discontinued. A 4-year follow-up revealed no
evidence of vitiligo. In conclusion, the possible occurrence of a transient
leucoderma in untreated areas should be included among the side effects of
contact immunotherapy of alopecia areata with squaric acid dibutylester.
PMID- 9649676
TI - Longterm remission of tumor-stage mycosis fungoides following total-skin electron
beam radiotherapy.
AB - We report the case of a patient with mycosis fungoides, stage II B with
generalized plaques and ulcerated tumors in a severely reduced general condition,
with anemia and extremely poor compliance, who was successfully treated with
total-skin electron-beam radiotherapy with a less severe relapse after more than
three years.
PMID- 9649677
TI - Coagulation factor XIII in scleroderma.
AB - The ability of blood coagulation factor XIII (FXIII) to affect collagen synthesis
and degradation led to its use in the treatment of scleroderma. Encouraging
initial results were achieved principally in terms of skin sclerosis,
musculoskeletal involvement and weakness. Further assessment of this treatment in
scleroderma was abandoned when, following the HIV epidemic, FXIII use became
strictly regulated. Safer concentrates are now available which may allow us to
reconsider this therapy. This paper, which briefly reviews available data related
to FXIII use in scleroderma and which proposes general rules for prescribing, is
aimed at generating an open debate as to the need to widen the regulated use of
FXIII to scleroderma.
PMID- 9649678
TI - Adhesion molecule expression in basal cell carcinoma.
AB - Basal cell carcinomas (BCCs) are frequently associated with a peritumoral
mononuclear infiltrate. Until now, the function of this inflammatory infiltrate
and its possible role in the control of tumor growth is unclear. Mechanisms
controlling endothelial and target cell adhesiveness for leukocytes are important
features in the development of a specific local immune response. The expression
and distribution of the adhesion molecules ICAM-1, VCAM-1 and E-selectin by
microvascular endothelial cells and tumor cells, together with their leukocyte
receptors LFA-1, VLA-4 and CLA respectively, were studied in 33 BCCs of different
histological subtypes. In normal skin, ICAM-1 is expressed by resting endothelial
cells, whereas VCAM-1 and E-selectin expression correlates with endothelial
activation. The epidermis in normal conditions displays no ICAM-1, VCAM-1, or E
selectin expression. In BCC, endothelial ICAM-1 expression was only slightly
increased compared to normal skin, whereas expression of endothelial VCAM-1 and E
selectin was low or absent in all BCCs examined. Peritumoral infiltrates
contained mostly LFA-1-expressing lymphocytes, with minimal VLA-4 and CLA
positivity. In none of the cases studied was adhesion molecule expression by BCC
tumor cells identified. The lack of significant expression of adhesion molecules
on peritumoral vascular endothelial cells and BCC tumor cells does not support
the idea of specific, cell-mediated immunity being an important mechanism in
limiting BCC tumor spread.
PMID- 9649679
TI - Shaving: a simple and effective treatment for moderate congenital hypertrichosis.
AB - Congenital hypertrichosis is a rare disorder. It is sometimes associated with
facial dysmorphism, and dental and gingival abnormalities. This condition
constitutes an esthetic problem and regular shaving with a simple razor can be a
simple method of treatment.
PMID- 9649680
TI - Pachyonychia congenita with steatocystoma multiplex. A report of two cases and a
discussion of the classification.
AB - Pachyonychia congenita is a rare syndrome in which the main and most common
clinical sign is onychodystrophy of all finger and toe nails. The most frequent
type of transmission seems to be autosomal dominant, but recessive forms have
also been described. Typical onychodystrophy can be associated with other
clinical manifestations. The most recent literature refers to descriptions of
about 250 cases up until 1993. Numerous classifications of pachyonychia congenita
have been suggested by several authors over the years. We report two cases of
pachyonychia congenita in association with steatocystoma multiplex in a mother
and son.
PMID- 9649681
TI - Purpuric lichen nitidus.
AB - We report the case of a patient in whom lichen nitidus with hemorrhage was found
on the palm and the thigh. Histopathologically, the small vessels in the lesions
showed extensive changes and were increased in number. The capillary walls
revealed degenerative changes with extravasation of erythrocytes. On electron
microscopy, amorphous, electron-dense deposits were observed along the outside of
the endothelial cells. These findings can explain the presence of the hemorrhagic
changes. We describe this as a case of purpuric lichen nitidus.
PMID- 9649682
TI - Expression of the bcl-2 homologue bax in normal human skin, psoriasis vulgaris
and non-melanoma skin cancers.
AB - Bax (bcl-2-associated X protein) is a recently identified member of the bcl-2
family and one of the principal inducers of apoptosis. We examined the
distribution of bax protein in normal human skin and several skin diseases by
immunohistochemistry. Bax immunoreactivity was present in normal epidermis and
its appendages, with the suprabasal compartment being stained more strongly than
basal keratinocytes. Bax immunostaining was also detected in the epidermis of
psoriasis vulgaris and 5 keratoacanthomas examined. We could observe only weak
bax immunoreactivity in 15 squamous cell carcinomas examined, with the exception
of well-differentiated tumour islands in two tumours, which expressed
immunostaining for bax comparable to that of normal suprabasal epidermis.
Immunostaining for bax was negative in 12 out of 17 basal cell carcinomas and the
remaining five tumours showed weak bax reactivity in tumour cells scattered
within tumour masses and in palisading layers of some tumour formations. Western
blot analysis confirmed the expression of bax protein in normal skin, psoriasis
vulgaris and squamous cell carcinoma as well as the absence of bax in basal cell
carcinoma. Our findings suggest that the loss of pro-apoptotic bax protein in
basal cell carcinoma and its reduced expression in squamous cell carcinoma might
be an important step in the development of these two skin cancers.
PMID- 9649683
TI - Development of pemphigus foliaceus in a patient with psoriasis: a simple
coincidence?
AB - Several cases of psoriasis associated with bullous diseases have been reported in
the literature. Bullous pemphigoid is the most frequent association observed,
while pemphigus-related disorders are less frequently described. The authors
report a case of a patient with long-standing psoriasis who developed pemphigus
foliaceous and discuss the possible relationship between the diseases.
PMID- 9649684
TI - Mechanisms of UV-induced immunosuppression. Link between UV-induced tolerance and
apoptosis.
PMID- 9649685
TI - Ultraviolet A radiation-induced immunomodulation: molecular and photobiological
mechanims.
PMID- 9649686
TI - Post-kala-azar dermal leishmaniasis.
AB - Post-kala-azar dermal leishmaniasis is a dermatosis which was described during
the first quarter of this century. Most cases reported are from the Indian
subcontinent and certain parts of Africa. The disease generally follows an attack
of kala-azar, usually a few months to several years after the visceral disease
has healed. The clinical picture is variable. In this report, we present a case
of post-kala-azar dermal leishmaniasis in a 5-year-old Iranian boy who presented
with multiple, asymptomatic, erythematous papules on his trunk and extremities
and a brownish, figurate discoloration on his lower extremities, 4 years after an
attack of kala-azar which was completely cured. Histopathological examination of
one of the biopsied papules revealed multiple Leishman bodies. The patient was
successfully treated with a pentavalent antimonial compound.
PMID- 9649687
TI - The antipsoriatic dimethyl-fumarate suppresses interferon-gamma -induced ICAM-1
and HLA-DR expression on hyperproliferative keratinocytes. Quantification by a
culture plate-directed APAAP-ELISA technique.
AB - The derivatives of fumaric acid show antipsoriatic effects but details of the
mechanism of action are largely unknown. The study focused on the effect of
fumaric acid, dimethyl-fumarate, Zn-, Ca- and Mg-monoethyl-fumarate on the
interferon-gamma (IFN-gamma)-induced expression of ICAM-1 and HLA-DR molecules on
keratinocytes. Human hyperproliferative keratinocytes of the HaCaT cell line were
exposed to IFN-gamma (10 U/ml) alone or in combination with fumaric acid and its
derivatives for 48 hrs. The effect of fumarates was investigated
semiquantitatively using the alkaline phosphatase-anti-alkaline phosphatase
(APAAP) method. Subsequently, the effect of dimethyl-fumarate, the main component
of "fumaric acid therapy", was evaluated quantitatively by means of an APAAP
ELISA technique. The semiquantitative evaluation revealed that in the micromolar
dose range investigated only dimethyl-fumarate demonstrated substantial growth
inhibition and down-regulation of the cell surface markers. In the quantitative
evaluation, dimethyl-fumarate significantly (p=0.05) suppressed the expression
of ICAM-1 (84%) and HLA-DR (67%) on HaCaT keratinocytes at a subtoxic
concentration of 4.0 microM as compared to untreated controls (100%). In
contrast, concentrations of 4.0, 12 and 35 microM dimethyl-fumarate had no
influence on the ICAM-1 and HLA-DR expression on IFN-gamma-exposed normal human
epidermal keratinocytes in primary cultures. Thus, there is experimental evidence
that dimethyl-fumarate may exert its antipsoriatic effect not only as an
antiproliferative agent but also by down-regulation of ICAM-1 and HLA-DR
molecules on hyperproliferative keratinocytes.
PMID- 9649688
TI - Multiple basal cell carcinoma developing two years after 60Co irradiation.
AB - A 66-year-old Japanese man developed multiple basal cell carcinoma 2 years after
receiving 60Co irradiation for oropharyngeal tumors. All of the tumors were
located within the radiation fields where the skin was atrophied and
telangiectatic. In the present case, the total dose (112 Gy) of 60Co radiation
received by the patient had been large and the latent period was much shorter
than in previously reported cases. It is suggested that the reasons for the short
latency in our case were 1) the total radiation dose and 2) the fact that the
area irradiated was a frequently sun-exposed area.
PMID- 9649689
TI - 99mTc-MIBI uptake in a primitive leptomeningeal melanoma.
AB - Primitive leptomeningeal melanoma is a rare and aggressive condition. The authors
report on a case of primitive leptomeningeal melanoma imaged with 99mTc-Sestamibi
(MIBI). There was an intense accumulation of the radiotracer in the frontal and
parietal leptomeningeal regions and even after injections of gadolinium the MRI
continued to reveal a cystic image of the brain. In view of the diagnosis, MRI
demonstrated only limited usefulness. On the other hand, this case highlights the
important role of MIBI for the imaging of malignant tumors.
PMID- 9649690
TI - Acne-like eruption induced by pseudoxanthoma elasticum: effectiveness of liquid
nitrogen cryotherapy.
AB - We report a case of pseudoxanthoma elasticum associated with an acneiform
eruption involving the cervical area. When she was 16 years-old our patient was
diagnosed with pseudoxanthoma elasticum, affecting the skin (flexural, cervical
and neck areas) and the eyes (bilateral ocular angioid streaks). Ten years later,
acneiform lesions (inflammatory and comedones) developed on these lesions: - the
inflammatory lesions were characterized by phagocytosis of pathological elastic
fibers inducing granuloma - the histological aspects of pseudoxanthoma elasticum
were observed around large comedones. This association is rarely reported and we
think that atypical, cervical acneiform lesions may be an indication of
pseudoxanthoma elasticum. The mechanism for this association is not clearly
understood. In our case, Von-Kossa staining was negative for the granulomatous
lesions and positive for the comedones: calcification could protect elastopathic
fibers from phagocytosis. Treatment is difficult: anti-acneic treatments are not
effective except for tetracylines, the anti-inflammatory effects of which can
improve granulomatous lesions. As its efficacy has been reported in elastosis
perforans serpiginosa, we used liquid nitrogen cryotherapy on the inflammatory
lesions with good results (separation of epidermis from dermis perhaps promoting
transepithelial elimination of the abnormal dermal elastic tissue).
PMID- 9649691
TI - Are local and systemic conditions important for the development of onychomycosis?
AB - Available epidemiological data indicate that the prevalence of onychomycosis due
to dermatophytes increases with ageing. The aim of this study was to investigate
the epidemiology of dermatophyte nail infections in 2 populations selected only
on an age basis and to verify whether the presence of onychomycosis was
associated with increased exposure to possible predisposing factors. From January
to June 1995, the nails of 1,800 military recruits and 253 elderly individuals
living in a nursing home were examined. Mycological studies were performed in all
cases of suspected onychomycosis. The presence of systemic or local diseases that
may favor fungal nail infection as well as exposure to environmental factors were
assessed in the 2 populations. Onychomycosis was diagnosed in 8 recruits (0. 44%)
and 38 of the elderly people (15%). The presence of onychomycosis was not related
to the degree of exposure to environmental factors or to systemic or local
diseases.
PMID- 9649692
TI - Angiolymphoid hyperplasia with eosinophilia.
AB - We report a case of angiolymphoid hyperplasia with eosinophilia (ALHE).
Histologically, some vessels were lined with plump endothelial cells.
Infiltration by lymphocytes, histiocytes and eosinophils was marked. An
arteriovenous malformation and vessels occluded by endothelial cell hyperplasia
were present. PCNA staining gave positive results for the nuclei of many of the
plump endothelial cells. Electron-microscopic findings disclosed increased
metabolic activity in the cells. These observations suggest that the plump
endothelial cells, characteristic of ALHE, have high metabolic activity. These
results suggest that blood flow is increased by arteriovenous malformations and
that blood pressure is elevated by occlusion, resulting in hyperplasia of plump
endothelial cells and accelerated neovascularization.
PMID- 9649694
TI - Analysis of T cell receptor Vbeta repertoires of annular erythema associated with
Sjogren's syndrome.
AB - Sjogren's syndrome (SjS) is an autoimmune disorder characterized by lymphocytic
infiltration into the lacrimal and salivary glands. Annular erythema has recently
been reported to be a specific, cutaneous manifestation associated with SjS. In
this study, the T cell receptor (TCR) Vbeta gene usage and expansion was examined
in annular erythema associated with SjS (AESjS) in 7 patients with primary SjS (5
definite and 2 probable), using reverse transcriptase polymerase chain reaction
(RT-PCR) amplification of 22 Vbeta gene families. For 4 out of the 7 patients,
the TCR V repertoire in lesional skin of AESjS was compared with paired
peripheral blood mononuclear cells (PBL). In one case, two lesional tissue
specimens biopsied from different sites of AESjS (face and trunk) were examined.
As a control, the TCR Vbeta repertoire was examined from the lesional skin of
butterfly rash biopsied from 3 cases of systemic lupus erythematosus (SLE).
Results showed that TCR Vbeta 2 was detected in 6 out of the 7 cases of AESjS,
although diverse usage was observed. TCR Vbeta 2 and 17 (but particularly Vbeta
2) were predominantly expressed in AESjS in comparison with paired PBL. In the
case which presented AESjS at two separate sites, Vbeta 2, 6, 18 and 19 were
preferentially expressed in both skin sites as compared with PBL. On the other
hand, TCR Vbeta 6, 13-2 and 14 were commonly demonstrated in the cutaneous
lesions of SLE. These results suggest that (1) the TCR Vbeta usage by
infiltrating T cells in AESjS is not strictly limited, however, Vbeta 2 may play
an important role in the induction of AESjS, and that (2) different subsets of
TCR Vbeta genes are used in the lesional skin of SjS and SLE, which might account
for the clinical and histological differences seen in the erythema found in these
two autoimmune disorders.
PMID- 9649695
TI - Subcutaneous interleukin-2 and interferon-alpha therapy associated with cisplatin
monochemotherapy in the treatment of metastatic melanoma.
AB - The anti-tumoral activity of interleukin-2 (IL-2) is well-documented. Although
the response rate with this cytokine is low, it appears to be improved when
associated with interferon-alpha (INF-alpha) and/or cytotoxic drugs. Aim of this
work was to study the efficacy and tolerance of an ambulatory treatment using
subcutaneous, low-dose IL-2 with subcutaneous INF-alpha and chemotherapy. We
report a multicenter study of ambulatory treatment combining subcutaneous (SC)
low-dose IL-2 (9 x 10(6) IU) with SC INF-alpha-2a (3 x 10(6) IU) and cisplatin
(100 mg/m2) in 33 patients (13 women and 20 men, 22 to 66 years of age) with
metastatic malignant melanoma. Metastases were mainly nodal (54.5%) and pulmonary
(51.5%). For 81.8% of patients, this therapy constituted the firstline treatment.
The overall response rate at the end of the first maintenance course was 30.3% (3
complete responses and 7 partial responses). Adverse effects were observed in 28
patients (84.8%), but were most often minor (grade 1 or 2 on the WHO toxicity
scale). The results confirmed the good tolerance to SC IL-2 and its suitability
for ambulatory therapy, as well as the potential benefit of associating IL-2 with
cisplatin in the treatment of metastatic melanoma (a possibility considered in
two previous studies).
PMID- 9649696
TI - Disparate effects of photoprotection on ultraviolet radiation-induced
immunosuppression.
PMID- 9649697
TI - Lidocaine-prilocaine cream (EMLA Cream) as a topical anaesthetic for the
cleansing of leg ulcers. The effect of length of application time.
AB - Pain prevents the effective cleansing of many leg ulcers. Pain relief during
debridement has been reported after topical anaesthesia with EMLA cream. The
purpose of this study was to assess and compare the pain intensity during
debridement after different lengths of application time of EMLA. Fifty-nine
patients, stratified for leg ulcer type, were randomised to 10, 20 or 60 minutes
treatment with EMLA prior to debridement. The pain was rated by each patient on a
100-mm visual analogue scale (VAS). Pain intensity during debridement decreased
significantly with increasing duration of EMLA application (p = 0.001). The
median values of the VAS pain scores were 41, 20 and 8 in the 10-, 20- and 60-
minute groups respectively. A minimum of 20 minutes application time gives
substantial pain relief in the majority of patients.
PMID- 9649698
TI - Immunomodulation by UV light: role of neuropeptides.
PMID- 9649699
TI - Infundibulocystic basal cell carcinoma.
AB - We report on a 72-year-old male patient with a solitary, dome-shaped tumor on the
preauricular region. Histologically, it showed an intradermal basaloid cell tumor
composed of many anastomosing epithelial cords. There were multiple infundibular
cystic structures containing corneocytes lined by follicular infundibular
epithelium and bud-like structures simulating the follicular germs throughout the
neoplasm. Follicular bulbs and papillae were absent within the tumor. The stroma
was scant and not highly fibroplastic. The tumor was diagnosed as
infundibulocystic basal cell carcinoma, a recently described, uncommon variant of
basal cell carcinoma.
PMID- 9649700
TI - Guess what! Scrofuloderma (tuberculosis colliquativa cutis) of the left foot.
PMID- 9649701
TI - The chemokine family. Potential therapeutic targets from allergy to HIV
infection.
AB - Basal trafficking and homing of leukocytes is controlled by a large subfamily of
cytokines, the chemokines. The initiation and perpetuation of an inflammatory
response is also mediated by the chemokines. The chemokine family acts through a
sub-family of the seven transmembrane, G-protein-coupled receptor class. Despite
the large number of chemokine proteins, several factors such as regulated
expression of the ligands and their receptors, glycosoaminoglycan interactions
and their signaling mechanisms introduce the required selectivity in vivo.
Recently, chemokine receptors have been identified as an essential component for
the infection of host cells by HIV. Chemokine receptors thus present an
attractive therapeutic target for inflammatory disorders and HIV infection, and
evidence for their validation using antibodies and receptor antagonists is
discussed.
PMID- 9649702
TI - Unilateral demodicidosis.
AB - A 45-year-old man presented with a unilateral, papulopustular, rosacealike,
chronic dermatitis which involved the left portion of the forehead and the
eyelids unilaterally. Many Demodex mites were found in the follicles of the
affected area. Topical crotamiton cleared the lesions after an unsuccessful trial
with oral metronidazole. This observation provides further evidence that
demodicidosis is a condition distinct from common rosacea.
PMID- 9649703
TI - Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A
expression in rats.
AB - Cyclosporine A is a powerful immunosuppressive agent which is widely used for the
prevention of allograft rejection and for the treatment of autoimmune diseases.
Clinical and experimental data show that it may also act on connective tissue. We
investigated the influence of cyclosporine A on granulation tissue formation and
wound healing. Using an in vitro approach, we followed the time course of rat
dermal fibroblasts during wound repair. Granulation fibroblasts were compared to
dermal fibroblasts flow cytometrically and by mRNA analysis with respect to the
expression of procollagen alpha1(I), integrin beta1, interleukin-6, transforming
growth factor beta1, keratinocyte growth factor and activin betaA. The most
pronounced effect in cyclosporine-treated rats was the strong down-regulation of
activin beta expression. In cryo-sections of granulation tissue from the same
rats, the distribution and expression intensity of intercellular adhesion
molecule and its receptors were investigated by immunohistology. Clearly, a time
course was detectable. Tissue from CsA-treated animals showed a delay of three
days compared to untreated animals. Apoptosis was also delayed in CsA-treated
rats by around three days. Furthermore, we investigated the effect of CsA on the
expression of collagen alpha1(I), fibronectin and matrix metalloprotease 1 genes
in dermal fibroblasts from untreated donors. No changes in the mRNA steady state
levels of these genes were revealed after direct addition of different doses of
CsA to fibroblast cultures. Our data suggest that CsA may interfere with the
complicated net of interactions between connective tissue and the immune system
by down-regulation of the inflammatory phase by modulation of cytokines and a
subsequent delay of tissue repair.
PMID- 9649704
TI - Immunomodulation induced by psoralen plus ultraviolet A radiation.
PMID- 9649705
TI - Sporadic generalized lentiginosis without systemic involvement.
AB - A 42-year old Caucasian man with generalized, acquired lentiginosis and no other
associated diseases is described. A brief discussion about the significance of
the term lentiginoses, the problems of their classification and nomenclature is
also presented. The presence at the histopathologic examination, of some
junctional nests of melanocytes provides the basis for a discussion of the
relationship of the case presented, as well as other lentiginoses, with
melanocytic naevi.
PMID- 9649706
TI - Relevance of photo-immunosuppression for viral infections (i.e. human papilloma
virus).
PMID- 9649707
TI - Pathogenesis of leukocytoclastic vasculitis.
AB - There is compelling animal and human experimental evidence that leukocytoclastic
vasculitis is a hypersensitivity vasculitis, similar in nature to the
experimental Arthus reaction. The immune complexes formed in antigen excess
circulate until some event occurs that cause deposition in blood vessel walls.
Adhesion molecules and cytokines released by endothelial cells and activated
neutrophils represent a key factor in this process. The membrane attack complex
of complement plays a significant role in altering the endothelial cell membrane
integrity. Activated neutrophils release proteolytic enzymes, especially
collagenases and elastases, along with free oxygen radicals that damage the
vessel walls and the surrounding tissues. It remains uncertain whether
antineutrophilic cytoplasmic antibodies, anti-endothelial antibodies and anti
cardiolipin antibodies are epiphenomena or are directly involved in the disease
process. Apoptotic cell death mediated by the Fas/Bc12 system is a feature of
leucocytoclastic vasculitis. In conclusion, the post-capillary venule is the
active orchestrator of neutrophils in leukocytoclastic vasculitis which mediate a
complex series of endothelial/leukocyte interactions.
PMID- 9649708
TI - Photoprotection and photo-immunosuppression in man.
PMID- 9649709
TI - Variable expression of Mn SOD in three different human melanoma cell lines.
AB - In recent studies, decreased expression of Mn SOD, an intramitochondrial enzyme
responsible for the dismutation of anion superoxide, has been reported in
multiple, malignant cell types, whereas its gene has been proposed as a tumour
suppressor gene in melanoma. We studied the expression of Mn SOD both at genetic
(DNA, mRNA) and protein levels in three human melanoma cell lines (M3 Da, M4 Be,
M1 Do). All cell lines were tumorigenic in a nude mouse model. In these cell
lines, Mn SOD was studied at the molecular level using PCR of genomic DNA, and by
RT-PCR of total mRNA extracts to detect Mn SOD transcripts. Mn SOD protein
expression was studied by indirect immunofluorescence using a monoclonal antibody
anti-human Mn SOD (Bender) on suspended cells fixed on slides after cytospin. All
three human melanoma cell lines studied contained detectable amounts of DNA and
mRNA specific for the Mn SOD gene. In contrast, there was variable expression of
Mn SOD at the protein level. As detected by immunofluorescence, Mn SOD protein
was expressed in only two cell lines (strongly in M3 Da, weakly in M4 Be) but not
in M1 Do. These preliminary, qualitative results demonstrate that the deficit of
Mn SOD protein expression is variable depending on the particular melanoma cell
line. Further investigations are required in order to evaluate quantitative Mn
SOD protein expression and activity as well as the level of functional Mn SOD
mRNA and DNA in these or other cell lines.
PMID- 9649710
TI - An immunohistochemical study of UV-induced skin lesions in actinic prurigo.
Resistance of langerhans cells to UV light.
AB - Actinic prurigo is an inflammatory disease of the skin that appears to be
mediated by an abnormal immune response. Cell adhesion molecules play a key role
in the induction of the immune response as well as in the pathogenesis of
inflammation. We investigated the expression of cell adhesion and activation
molecules, as well as the density of Langerhans cells in skin from patients with
actinic prurigo. Skin biopsies from ultraviolet light-induced lesions, and non
irradiated areas from 10 actinic prurigo patients were studied; in addition,
several spontaneous skin lesions were studied. Skin biopsies from normal
individuals were used as controls. The expression of ICAM-1, ICAM-3, LFA-3, CD2,
LFA-1, VLA-4, CD1a, VCAM-1, CD69, and activated b1 integrins were assessed by
immunostaining. An increased expression of LFA-1, LFA-2, ICAM-3, VLA-4, and
activated b1 integrins was observed in the cell infiltrate of actinic prurigo
lesions and an up-regulated expression of ICAM-1 was detected in keratinocytes
from these specimens. Interestingly, the number of Langerhans cells (CD1a + ) in
actinic prurigo skin was not significantly affected by ultraviolet irradiation, a
phenomenon that was not observed in normal controls. The increased expression of
adhesion molecules in the cell infiltrate of actinic prurigo, indicates that
these cells are activated and suggests that they are involved in the skin damage
seen in these patients. The resistance of Langerhans cells from patients with
actinic prurigo to ultraviolet light may have an important role in the
pathogenesis of this condition. The involvement of keratinocytes in the
pathogenesis of actinic prurigo is suggested by the expression of ICAM-1 on these
cells.
PMID- 9649711
TI - Annular elastolytic sarcoidosis of the face.
AB - We report a case of facial annular lesions in a non-diabetic, Japanese woman aged
78, the histopathological study of which showed noncaseating, epithelioid cell
granuloma with multinucleated giant cells. Together with the aberrant laboratory
data, these clinical and histopathological findings were considered to be
compatible with those of sarcoidosis, but elastic tissue stain disclosed the
existence of elastolytic changes which were clinically and histopathologically
similar to those found in actinic granuloma or annular elastolytic giant cell
granuloma. Based on a review of the literature, we believe that several annular
elastolytic granulomatous diseases of the face form a disease spectrum, some of
which are identified with intermediate features of these three diseases.
PMID- 9649712
TI - The pathophysiology of lupus erythematosus.
AB - Systemic lupus erythematosus disseminatus in addition to the more restricted,
lupus-like syndromes, is the consequence of an attack by the immune system on the
cellular and nuclear structures of the body. These disorders are also frequently
associated with disturbances of the coagulation cascade. In this review paper,
the factors that provoke or enhance these disturbances are considered, as well as
the way by which this provocative effect is exerted. An intermutual relation
between various elements is described, whereby congenital factors (heredity,
race) and non-congenital factors (sex hormones, pregnancy, environment,
ultraviolet light, drugs, infection) play a role. These factors induce the
activation cascade of the disease, via two different axes: on the one hand
modifications in the DNA structure, on the other immune stimulation. This
eventually results in tissue damage.
PMID- 9649713
TI - Pyoderma gangrenosum associated with the secondary antiphospholipid syndrome.
AB - A 64-year-old woman with an 11-year history of systemic lupus erythematosus and
amputation of her left lower leg as a consequence of arterial embolism, presented
with two large, non-healing ulcers on her right shank. Pyoderma gangrenosum
associated with secondary antiphospholipid syndrome was diagnosed based upon the
typical clinical features and increased antibodies to cardiolipin. Although an
aggressive therapy with corticosteroids and cyclosporine was started, her
condition continued to worsen. She finally died as a result of sepsis. We discuss
the difficulties in diagnosis and therapy of SLE combined with the
antiphospholipid syndrome and pyoderma gangrenosum.
PMID- 9649714
TI - Gowers' local panatrophy.
AB - We report a patient with Gowers' local panatrophy, who developed skin atrophy on
the left upper arm, right lower leg and facial hemiatrophy without a thickening
or a sclerosing process. Histological examination revealed loss of thickness of
the dermis and subcutaneous tissue. It is suggested that skin atrophy was induced
by a nonsclerosing process, different from the inflammation and fibrosis observed
in scleroderma.
PMID- 9649715
TI - Neurofibromatosis type 1 associated with systemic vasculopathy.
AB - Systemic vasculopathy in patients with neurofibromatosis type 1 is rare. We
describe a case of unusual cerebral and renal involvement in a young, 29-year-old
patient, who died of a cerebral ischemic attack one year after our observation.
PMID- 9649716
TI - Immunocytochemical demonstration of reduced Cu,Zn-superoxide dismutase levels
following topical application of dithranol and sodium lauryl sulphate: an
indication of the role of oxidative stress in acute irritant contact dermatitis.
AB - Oxidative stress is known to be implicated in the inflammation induced by the
anti-psoriatic irritant, dithranol. In this study, we wished to investigate
whether this is reflected in the levels of the antioxidant enzyme, Cu,Zn
superoxide dismutase, as detected by quantitative immunocytochemistry, and
whether similar changes also occur following exposure to an irritant not normally
associated with reactive oxygen species generation, namely sodium lauryl
sulphate. Analysis of biopsies from patch test sites revealed that significant
reductions in the epidermal levels of Cu,Zn-superoxide dismutase were induced by
both dithranol and sodium lauryl sulphate, although the time course of diminished
activity was different for each irritant. Our findings suggest that oxidative
stress plays a general role in the pathophysiology of acute irritant contact
dermatitis.
PMID- 9649717
TI - A case of chromoblastomycosis due to Phialophora verrucosa responding to
treatment with fluconazole.
AB - We report the case of a 40-year-old Filippino woman, with a 5-year history of a
slowly spreading, painful skin lesion on her left foot. Histological examination
showed a dermal, granulomatous infiltrate consisting of neutrophils, histiocytes
and lymphocytes, with "sclerotic bodies" in the cytoplasm of phagocytic cells.
Mycological culture revealed the presence of Phialophora verrucosa and confirmed
the histopathological diagnosis of chromo-blastomycosis. Association of surgical
curettage of the exuberant, infected tissue with systemic fluconazole
administration gave good therapeutic results with no relevant side effects.
PMID- 9649718
TI - Segmental arrangement of multiple, partly congenital and partly acquired
melanocytic nevi.
AB - A 15 year-old girl presented with numerous congenital melanocytic nevi,
occasionally hairy, with a segmental distribution at the left pre-auricular
region. On the left side of the back of the neck there were multiple melanocytic
nevi with a warty appearance, which had started to appear when she was 5 and
which had remained stable from the time she was 10. These lesions had a
distribution reminiscent of an epidermal nevus with a pattern similar to
Blaschko's lines. On general physical examination there was a moderate degree of
idiopathic scoliosis, with a left lumbar curvature. Biopsies were taken from both
types of nevus which were diagnosed as congenital compound melanocytic nevus and
acquired compound melanocytic nevus respectively. We consider that the segmental
distribution of the melanocytic nevi of this patient supports the theory that a
genetic defect determined the appearance of both these congenital and acquired
lesions.
PMID- 9649719
TI - Melanin and melanosome complexes in long standing stable vitiligo--an
ultrastructural study.
AB - To investigate the presence of melanin and melanocytes (MC) in stable vitiligo,
skin biopsies from five patients with vitiligo lesions of between 1 to 17 years
duration were examined under the electron microscope. Areas of the upper dermis
and epidermis were explored. There was a significant amount of melanin in a few
keratinocytes (KC) grouped in the stratum basale in 1-3 year-old vitiligo
lesions. In these KC, the melanosomes were most often aggregated into melanosome
complexes (MCo) while the remaining KC were completely devoid of melanin.
Solitary MCo were also observed in a few dermal cells in all vitiligo biopsies.
All non-keratinocytes were scrutinized in series of 200-300 consecutive sections
and were identified according to morphological characteristics. Neither active
nor inactive MC, nor MC dendrites were found. These observations show that
melanin in non-negligible amounts can be found even in 3 year-old vitiligo
epidermis. Since there were no MC detected in the epidermis it implies that the
melanosomes can persist in certain KC for some time after the onset of vitiligo.
PMID- 9649720
TI - Findings in vivo of Sarcoptes scabiei with incident light microscopy.
AB - Parasites, especially Sarcoptes scabiei, may represent a difficult diagnostic
problem. In many cases, the results of the usual methods for the diagnosis of
scabies, such as microscopic identification, can be negative owing to the small
number of parasites present in the cornified layer. Moreover, tape stripping or
removal of mites with a needle is difficult and sometimes painful, and therefore,
not well accepted. We have evaluated the applicability and usefulness of
epiluminescence microscopy, a new technique frequently used for the study of
pigmented lesions of the skin. Thirty seven patients with the presumptive
clinical and/or anamnestic diagnosis of scabies were enrolled in our study. With
this method many suspicious sites may be examined within a few minutes without
causing any harm or discomfort to the patient.
PMID- 9649721
TI - Prologue: placental-fetal metabolic inter-relationships.
PMID- 9649722
TI - An overview of early post-partum nutrition and metabolism.
PMID- 9649723
TI - Nutrient and metabolic needs of the fetus and very small infant: a comparative
approach.
PMID- 9649724
TI - Fuel selection: the maternal adaptation to fetal nutrient demand.
PMID- 9649725
TI - Mechanisms of maternofetal exchange across the human placenta.
PMID- 9649726
TI - Maternal nutrition and disproportionate placental-to-fetal growth.
PMID- 9649727
TI - Long-chain polyunsaturated fatty acids: who needs them?
PMID- 9649728
TI - Milk: integrative signalling between mother and offspring.
PMID- 9649729
TI - Environmental contaminants in milk: the problem of organochlorine xenobiotics.
PMID- 9649730
TI - Role of long-chain fatty acids in the postnatal induction of genes coding for
liver mitochondrial beta-oxidative enzymes.
PMID- 9649731
TI - Neonatal brown adipose tissue, UCP1 and the novel uncoupling proteins.
PMID- 9649732
TI - Neonatal metabolic adaptation after preterm delivery or intra-uterine growth
retardation.
PMID- 9649733
TI - Impaired neonatal hepatic ketogenesis.
PMID- 9649734
TI - Total parenteral nutrition in surgical infants.
PMID- 9649735
TI - Inborn errors of ketogenesis.
PMID- 9649736
TI - Inborn errors of metabolism in the light of metabolic control analysis.
PMID- 9649737
TI - Recent developments in the detection of inherited disorders of mitochondrial beta
oxidation.
PMID- 9649738
TI - Glycosidase families.
PMID- 9649739
TI - Mechanisms of cellulases and xylanases.
PMID- 9649740
TI - The cellobiohydrolases of Trichoderma reesei: a review of indirect and direct
evidence that their function is not just glycosidic bond hydrolysis.
PMID- 9649741
TI - Kinetics of fungal cellulases.
PMID- 9649742
TI - Structural studies on cellulases.
AB - Recent advances in chemical methodologies, together with the technique of X-ray
structure analysis, are providing profound structural and mechanistic insights
into cellulase action. At the structural level, detailed analyses of nearly all
the enzyme families involved in cellulose breakdown are not known.
Oligosaccharide complexes for all these enzymes have not yet been described, but
utilization of the chemistry provided by non-hydrolysable oligosaccharides,
sugars modified so as to provide long-lived glycosyl-enzyme intermediates, and
the development of transition-state analogues, should soon extend and develop our
knowledge of these systems. The way in which enzyme structure dictates reaction
chemistry is beginning to be more clearly understood.
PMID- 9649743
TI - Trichoderma reesei cellobiohydrolases: why so efficient on crystalline cellulose?
PMID- 9649744
TI - The cellulosome of Clostridium thermocellum.
PMID- 9649745
TI - Structure and function analysis of Pseudomonas plant cell wall hydrolases.
PMID- 9649746
TI - Superfamilies: the 4/7 superfamily of beta alpha-barrel glycosidases and the
right-handed parallel beta-helix superfamily.
PMID- 9649747
TI - Structure, function and protein engineering of starch-degrading enzymes.
PMID- 9649748
TI - Specificity of ferulic acid (feruloyl) esterases.
PMID- 9649749
TI - Molecular and intracellular events in the assembly and secretion of chylomicrons
by enterocytes.
PMID- 9649750
TI - The role of gastrointestinal hormones in carbohydrate and lipid metabolism and
homeostasis: effects of gastric inhibitory polypeptide and glucagon-like peptide
1.
PMID- 9649751
TI - Modification of the gut flora by dietary means.
PMID- 9649752
TI - Effect of non-digestible fermentable carbohydrates on hepatic fatty acid
metabolism.
PMID- 9649753
TI - Salvage of urea-nitrogen in the large bowel: functional significance in metabolic
control and adaptation.
PMID- 9649754
TI - Bcl-2 as a possible sensor of nutritional stress inhibiting apoptosis and
allowing cell survival during colorectal carcinogenesis.
PMID- 9649755
TI - Plasmalogen-selective phospholipase A2 and its involvement in Alzheimer's
disease.
PMID- 9649756
TI - The role of docosahexaenoic acid in brain development and fetal alcohol syndrome.
PMID- 9649757
TI - Do long-chain polyunsaturated fatty acids influence infant cognitive behaviour?
PMID- 9649758
TI - Role of apolipoprotein E in modulating neurite outgrowth: potential effect of
intracellular apolipoprotein E.
PMID- 9649759
TI - Apolipoprotein E and neuronal plasticity following experimental de-afferentation
and in Alzheimer's disease.
PMID- 9649760
TI - Pharmacological, physiological and clinical implications of the discovery of
cannabinoid receptors.
PMID- 9649761
TI - Herpes simplex virus type I in brain and the type 4 allele of the apolipoprotein
E gene are a combined risk factor for Alzheimer's disease.
PMID- 9649762
TI - A simple method for the extraction and quantification of daidzein and genistein
in food using gas chromatography mass spectrometry.
PMID- 9649763
TI - Flux control exerted by mitochondrial outer membrane carnitine
palmitoyltransferase over ketogenic flux in hepatocytes isolated from suckling
rats.
PMID- 9649764
TI - Gestational and neonatal expression and activity of human hepatic 3-hydroxy-3
methylglutaryl-CoA synthase.
PMID- 9649765
TI - Effect of maternal fatty acid supply on umbilical cord and piglet tissue
composition.
PMID- 9649766
TI - Beta-oxidation in neonatal cardiac mitochondria.
PMID- 9649767
TI - Ca2+ inhibits Mg(2+)-mediated trophoblast cell adhesion to extracellular matrix
in vitro.
PMID- 9649768
TI - Transition metal cations potently mediate adhesion of trophoblast cells to
extracellular matrix in vitro.
PMID- 9649769
TI - Choline metabolism in the neonatal period.
PMID- 9649770
TI - The general transcription factor Sp1 plays an important role in the regulation of
fatty acid synthase.
PMID- 9649771
TI - Expression of a sodium-dependent L-carnitine transporter in lactating rat mammary
tissue.
PMID- 9649772
TI - Prematurity: influence of atopic status and infant feeding practices on specific
IgG levels in cord and infant serum.
PMID- 9649773
TI - Hyperleptinaemia precedes hyperinsulinaemia in Zucker (fa/fa) rats.
PMID- 9649774
TI - Copper and iron interactions in a placental cell line (BeWo).
PMID- 9649775
TI - Growth sensitive genes expressed in the placenta.
PMID- 9649776
TI - The role of polyamines in pregnancy.
PMID- 9649777
TI - Changes in ferrozine detectable iron in liver cells during hypoxia and
hypothermia.
PMID- 9649778
TI - Screening for the trifunctional protein G1528C mutation in alcoholic liver
disease.
PMID- 9649779
TI - Problem-based learning in modular science degrees.
PMID- 9649780
TI - Are we getting W.I.S.E. (Women Into Science and Engineering) or do we still have
W.A.S.T.E. (Women Averse Science, Technology and Engineering).
PMID- 9649781
TI - Distribution and activities of neuronal protein 4.1 isotypes.
PMID- 9649782
TI - Intracellular localisation of beta I sigma 2 spectrin with GLUT4 vesicles.
PMID- 9649783
TI - A method for the measurement of [3H]-glutamate release from cultured dorsal root
ganglion neurons.
PMID- 9649784
TI - Interaction of synapsin IIb with calmodulin: identification of a high affinity
site.
PMID- 9649785
TI - Interaction of synapsin I with actin and SSVs: differential regulation by
calmodulin.
PMID- 9649786
TI - The effect of cytochalasin D and colcemid on noradrenaline release in the human
neuroblastoma SH-SY5Y.
PMID- 9649787
TI - CPT (8-cyclopentyl theophylline) corrects CFTR antibody inhibited mucin
secretion.
PMID- 9649788
TI - Remodelling glycans on IgG by genetic re-engineering.
PMID- 9649789
TI - Physiological influences on recombinant IgG glycosylation.
PMID- 9649790
TI - Genetic engineering of alpha 2,6-sialyltransferase in recombinant CHO cells.
PMID- 9649791
TI - Fragmentation patterns of human paranasal sinus mucins.
PMID- 9649792
TI - MUC5B expression in middle ear mucosal glands.
PMID- 9649793
TI - Protein glycosylation and peripheral vascular disease in diabetic patients.
PMID- 9649794
TI - Protein-protein and protein-lipid interactions of the CaLB domain.
PMID- 9649795
TI - Identification of a monocarboxylate transporter isoform type 1 (MCT1) on the
luminal membrane of human and pig colon.
PMID- 9649796
TI - Sequence comparisons of ruminant renal Na+/phosphate co-transporters.
PMID- 9649797
TI - Isolation of a RT-PCR fragment from human colon and sheep rumen RNA with
nucleotide sequence similarity to human and rat urea transporter isoforms.
PMID- 9649798
TI - Molecular modelling of the mechanism of bile acid transport by the hepatocyte
canalicular ecto-ATPase (CAM-105).
PMID- 9649799
TI - Does glutathione flush reduce acute cellular rejection in liver allografts?
PMID- 9649800
TI - Adhesion molecule activation and hepatocyte damage following orthotopic liver
transplantation (OLT).
PMID- 9649801
TI - A GFP-PKC fusion protein to investigate the mechanism of PKC down-regulation.
PMID- 9649802
TI - Serum total antioxidant status during vascular surgery.
PMID- 9649803
TI - Regulation of phospholipase C delta 1 activity by GTP-binding proteins: rhoA as
an inhibitory modulator.
PMID- 9649804
TI - Synthesis and characterization of tagged human oxytocin receptors (hOTRs).
PMID- 9649805
TI - ADP-ribosyltransferase inhibitors and pseudo-substrates inhibit rat smooth muscle
cell migration in vitro.
PMID- 9649806
TI - PPADS and extracellular ATP both mediate endothelial dependent relaxation of
guinea pig aorta.
PMID- 9649807
TI - Regulation of phospholipase C gamma 1 activity by GTP-binding proteins in
vascular smooth muscle.
PMID- 9649808
TI - Differential expression of phospholipase C delta 1 in Wistar Kyoto compared to
spontaneously hypertensive rats.
PMID- 9649809
TI - Streptozotocin-induced diabetes is associated with increased renal lipoxygenase
activity.
PMID- 9649810
TI - The significance of 2' and 3' aminoacylation of RNA in the origin of amino acid
homochirality.
PMID- 9649811
TI - Angiotensin-converting enzyme (ACE) gene polymorphism and alcoholism.
PMID- 9649812
TI - Angiotensin-converting enzyme (ACE) gene polymorphism in patients with
sarcoidosis.
PMID- 9649813
TI - Selective expression of a novel striated muscle protein.
PMID- 9649814
TI - Autocatalytic processing of mutant SIV-PR polyproteins.
PMID- 9649815
TI - Free radical analysis via ESR spectroscopy during vascular surgery.
PMID- 9649816
TI - Kinetics of reactive oxygen intermediate formation and apoptosis in human glioma
and glioma C6 cell line: effects of radiation and n-6 essential fatty acids.
PMID- 9649817
TI - Depletion of docosahexaenoic acid in red blood cell membranes of depressive
patients.
PMID- 9649818
TI - Interactions of nitric oxide, free radicals and polyamines in the membrane
pathology of schizophrenia.
PMID- 9649819
TI - The production of a transgenic rat expressing nerve growth factor using cell-type
specific keratin promoters.
PMID- 9649820
TI - Effect of insulin and serum on lipoprotein lipase in lactation.
PMID- 9649821
TI - C-terminal His6-tagged lecithin-cholesterol acyltransferase (LCAT) is
catalytically active.
PMID- 9649822
TI - Immunoaffinity-isolation of plasma lecithin-cholesterol acyltransferase (LCAT)
from patients with hepatic cirrhosis.
PMID- 9649823
TI - Plasma, platelet and erythrocyte lipids in the Watanabe heritable hyperlipidaemic
(WHHL) rabbit.
PMID- 9649824
TI - Chylomicron remnants derived from fish oil are bound and internalised more
rapidly by isolated hepatocytes than those derived from olive or palm oil.
PMID- 9649825
TI - Effects of oestrogen on plasma, hepatic and biliary cholesterol levels in rats
fed fish oil.
PMID- 9649826
TI - Biochemical studies of oil biosynthesis in olive (Olea europea) and oil palm
(Elaeis guineensis) callus cultures.
PMID- 9649827
TI - Characteristics of wheat seed lipase.
PMID- 9649828
TI - Genetic mechanisms involved in the adaptation of marine algae to heavy metal
pollution.
PMID- 9649829
TI - Reaction products of the lipoxygenase pathway in olive tissue cultures.
PMID- 9649830
TI - The effects of Iprodione on the lipid metabolism of Botrytis cinerea.
PMID- 9649831
TI - Trans monounsaturated fatty acid and the oxidation of low density lipoproteins.
PMID- 9649832
TI - Trans mono-unsaturated fatty acids and tissue factor activity in a monocytic cell
line.
PMID- 9649833
TI - Modulation of colonocyte proliferation and apoptosis by dietary fish oil in
experimental colorectal carcinogenesis.
PMID- 9649834
TI - The effect of prostaglandin E2 on the intracellular lipolysis of triacylglycerol
in cultured rat hepatocytes.
PMID- 9649835
TI - Crystallising the LH1-RC "core" complex of purple bacteria.
PMID- 9649836
TI - Effects of indomethacin on mitochondrial ATP synthesis.
PMID- 9649837
TI - Effects of indomethacin on mitochondrial oxygen uptake in intestine.
PMID- 9649838
TI - Adenosine deaminase activity: to be an useful marker in distinguishing pleural
effusions due to malignancy from tuberculosis.
PMID- 9649839
TI - Identification of active site residues in a ferulic acid esterase (FAE-III) from
Aspergillus niger.
PMID- 9649840
TI - Stability of feruloyl esterases from Aspergillus.
PMID- 9649841
TI - Properties of ferulate dimers from plant cell walls.
PMID- 9649842
TI - Three distinct ferulic acid esterases produced by Aspergillus niger have
specificities for different phenolic-sugar linkages in plant cell walls.
PMID- 9649843
TI - Enzymic hydrolysis of diferulates from wheat bran cell walls.
PMID- 9649844
TI - Plant cell wall degrading enzyme complexes from the cellulolytic rumen bacterium
Ruminococcus flavefaciens.
PMID- 9649845
TI - Determination of the catalytic site content of a polyclonal catalytic antibody
preparation.
PMID- 9649846
TI - Sensitivities of transition state geometries to P1-P2 binding in reactions of
papain and actinidin.
PMID- 9649847
TI - The kinetically influential ionizations of caricain D158N revealed by using 4,4'
dipyrimidyl disulfide as a reactivity probe.
PMID- 9649848
TI - Detection of a free enzyme isomerisation in actinidin catalysed hydrolysis.
PMID- 9649849
TI - The role of Mg2+ in biotin carboxylation in pyruvate carboxylase.
PMID- 9649850
TI - Production of a yeast cell wall degrading enzyme, beta-1,3-glucanase by
recombinant Bacillus subtilis.
PMID- 9649851
TI - Use of argentation TLC with GC to resolve C18:1 fatty acid isomers in test and
commercial spreads.
PMID- 9649852
TI - Effects of body size on postprandial lipid metabolism in postmenopausal women.
PMID- 9649853
TI - Effect of the bile acid: fatty acid ratio on in vivo essential fatty acid
absorption in the rat.
PMID- 9649854
TI - Functional expression of Na(+)-independent bile acid transport in Xenopus laevis
oocytes following injection with pig intestinal mRNA.
PMID- 9649855
TI - Sugar analogues as potential inhibitors of the intestinal Na+/glucose co
transporter (SGLT1).
PMID- 9649856
TI - Cloning and characterisation of the ovine intestinal Na+/D-glucose cotransporter
(SGLT1) promoter.
PMID- 9649857
TI - Trimethylamine N-oxide as a probable source of urinary dimethylamine in man; a
statistical approach.
PMID- 9649858
TI - Mechanisms of inhibition of hepatic secretion of very low density lipoproteins by
dietary fish oils.
PMID- 9649859
TI - Lactose [13C]Ureide as a marker for colonic fermentation and the deconvolution of
a complex 13CO2 breath test curve.
PMID- 9649860
TI - Pea flour digestibility and fermentability measured with 13C isotopes.
PMID- 9649861
TI - The effect of a three week high fat diet on the mouth to caecum transit time of a
high fat meal in humans.
PMID- 9649862
TI - Faecal concentrations of biologically active diacylglycerols in humans.
PMID- 9649863
TI - Influence of lipid content of testmeal on gastrointestinal handling and metabolic
partitioning of dietary lipid in young men.
PMID- 9649864
TI - Gastrointestinal transit adaptation to low- and high-fat cafeteria diets.
PMID- 9649865
TI - Gastrointestinal transit adaptation to high-fat diet in the rat.
PMID- 9649866
TI - Copper and iron homeostasis in mammalian cells and cell lines.
PMID- 9649867
TI - Feeding and vigilance behaviour of breeding ostriches (Struthio camelus) in a
farming environment in Britain.
AB - 1. Vigilance and feeding behaviour of male and female adult breeding ostriches
were recorded to determine feeding and scanning bout lengths, a time budget and
the pattern of vigilance immediately after food was provided. 2. Males were more
vigilant and fed for shorter periods than females immediately after concentrate
food was delivered but not throughout the whole day. 3. Most interscan periods of
males were below 40 s with a maximum of 90 s compared with most interscan periods
of females lasting less than 70 s with a maximum of 160 s. 4. Gender differences
in behaviour are attributed to increased male vigilance for predators and/or
conspecifics, and increased female feeding required for egg production and
greater opportunity to feed because of male vigilance.
PMID- 9649868
TI - Feather pecking in growers: a study with individually marked birds.
AB - 1. The aim of the present study was to investigate whether individual birds
specialise in feather pecking. Growers were individually marked and reared in
groups of 30 or 31 in pens with a slatted floor. At an age of 4 to 6 weeks
feather pecking was frequent in all pens. 2. On average 83% of all group members
(10 groups, experiment 1) were recorded at least once as initiator of a feather
pecking interaction. In each group 2 to 6 individuals feather pecked more than
twice as often as the average for the group, and were defined as 'high rate
peckers'. They initiated 39% of all recorded feather pecking interactions. 3.
Every interaction was classified (with increasing intensity) as pecking,
pinching, pulling or plucking. Compared to the others, 'high rate peckers' had
more of their feather pecking classified as plucking and less classified as
pecking. 4. There was no evidence that particular individuals specialised in
pecking at other specific birds, at specific areas of the body or at birds
engaged in specific activities. 5. Growers (3 groups, experiment 2) that had just
feather pecked engaged in more feather pecking during a subsequent 2-min focal
observation than control birds that had not pecked before the start of the
observation. 6. It was concluded that feather pecking interactions are clustered
in time and that the behaviour is not performed by just a few members of a group.
However, some individuals are characterised by relatively high rates and more
severe forms of feather pecking.
PMID- 9649869
TI - Factors affecting the use of perches in cages by laying hens.
AB - 1. Three experiments were carried out with ISA Brown laying hens housed in
individual cages with softwood perches of rectangular cross section fitted across
the width of each cage, to investigate factors affecting the tendency of hens to
lay their eggs from the perches and to use perches at other times. These factors
were perch width and angle and method of perch introduction. 2. In experiment 1
there were 4 treatments. Perches were 38 or 60 mm wide; half of each width were
flat and half were fixed at 8 degrees, parallel to the slope of the floor. In 2
similar trials (with 48 and 44 birds respectively, equally divided between
treatments) birds were moved to experimental cages already fitted with perches.
Birds with 38 mm, sloping perches laid less than one third of their eggs from the
perch (31% and 9% in the two trials) while those with the other designs laid more
than 80% from the perch. Narrow sloping perches were not otherwise aversive and
there was no consistent variation between treatments in total time perching. 3.
In experiment 2, 32 birds were allowed to start laying on the floor of the
experimental cages then perches were introduced at 24 weeks with 8 birds on each
of 4 treatments: 50 mm perches fixed flat and 38 mm perches fixed flat, and at 5
and 10 degrees respectively. Only 27% of eggs were laid from the perches with no
variation between treatments either in this behaviour or in total time perching.
4. Experiment 3 provided 24 of the birds from experiment 2 with double-length
perches to determine whether they showed preferences for the design features
under consideration. Either half the perch length was flat and half sloping at 10
degrees or half was 38 and half 50 mm wide. Again a relatively low proportion of
eggs was laid from the perches (18%) and birds showed no significant preference
for different perch designs as indicated by either how much they perched or where
they perched. 5. These results suggest that both perch design and the way pullets
are introduced to perches influence the proportion of perch-laid eggs. They
confirm that in some circumstances laying from perches can be a serious problem,
but that in other circumstances incidence can be reduced to a manageable
frequency. Perches may therefore be practical in commercial production without
increasing the number of cracked eggs. The results are also likely to be
applicable in cages with other facilities including nest boxes.
PMID- 9649870
TI - Wet litter and perches as risk factors for the development of foot pad dermatitis
in floor-housed hens.
AB - 1. An experiment was conducted to determine whether different moisture levels of
litter and perches with different hygienic conditions are involved in the
manifestation of foot pad dermatitis in White Leghorn layers. 2. Four different
treatments were compared: dry litter and dry perches; dry litter and wet perches;
wet litter and dry perches; and wet litter and wet perches. Temperature, pH, air
humidity and ammonia changes in the pens were monitored. 3. The mean prevalence
of foot pad lesions in groups 1, 2, 3 and 4 was 17%, 13%, 49% and 48%
respectively. The overall incidence of foot pad lesions in birds reared on dry
litter was 38%, and in birds reared on wet litter 92%. 4. When the air
temperature was above 20 degrees C, an increasing moisture content in the litter
was associated with an increasing incidence of foot pad dermatitis. However, when
the air temperature was below 20 degrees C there were no new cases of dermatitis
in any of the 4 treatments. There were no significant differences in litter pH or
ammonia between the 4 treatments when compared over the whole experiment. 5.
Although the incidence of lesions was not significantly affected by the presence
of wet perches, the area of the lesions tended to be in groups with wet patches
than in groups with dry perches. 6. It is suggested that moisture and temperature
are important contributing factors for the occurrence of foot pad dermatitis in
laying hens. Wet perches may contribute to the severity of such lesions.
PMID- 9649871
TI - Effect of cage area, cage height and perches on feather condition, bone breakage
and mortality of laying hens.
AB - 1. The health of 2 flocks of 896 ISA Brown laying hens were studied successively
over the years 1995 and 1996 under different caging conditions. Hens were kept in
groups of 4 in a total of 224 cages. The treatments (7 different types of cages)
differed in area per hen (450, 600 or 800 cm2) and height (40 or 60 cm). In the
large (800 cm2/hen) and high (60 cm cage) treatment, half of the cages were
equipped with perches (20 cm/hen). Each study lasted 48 weeks. 2. Feather
condition was found to be independent of cage type. 3. No differences were
apparent between the 7 treatments in tibia breaking strength (using the 3-point
breakage technique). A significant increase in humerus breaking strength was
observed in the high cages. The frequency of broken wings recorded after
slaughter was lower in high cages (23%) than in low ones (36%). 4. Mortality was
different between treatments. This was explained by a higher proportion of birds
killed by 'body cannibalism' in the 60 cm high cages, and by a higher proportion
of birds killed by 'vent cannibalism' in the cages with perches.
PMID- 9649872
TI - UK survey of broiler ascites and sudden death syndromes in 1993.
AB - 1. The mean incidence of deaths from ascites in the UK in 1993 was 1.4% (0.7% in
1991 and 0.9% in 1992) and 0.8% from sudden death syndrome (SDS). In total, the
economic loss to the UK Broiler Industry in 1993 as a result of these 2
conditions was 24 Pounds M. 2. Clear geographical differences emerged in the
occurrence of ascites, with, not only the lowest incidences being observed in
Northern Ireland, but also the peak of the mortality from ascites occurring much
later in the rearing cycle than in other regions on the mainland. 3. In all
regions the incidence of SDS was lower than that of ascites but the reason for
this disparity remains to be established. 4. Some of the variables associated
with the road transportation of day-old chicks from the hatchery to the farm
appeared to influence the incidence of ascites. These included distance or time
travelled, stocking density, internal lorry temperature and the length of time
the lorry was heated before transport as well as the time the shed was heated
before chick arrival. Temperature was also an important factor during growth
(brooding and finishing). 5. Negative pressure-powered ventilation was preferred
in most organisations but more ascites was seen with positive pressure
ventilation. However, the lowest incidence of ascites occurred with natural
ventilation. There was more ascites relative to shed orientation when the wind
direction was from the west compared to the east. 6. This survey identifies the
extent of the problem of broiler ascites in the UK and also highlights the
importance of good management control of day-old chicks, not only following
placement, but even before their arrival on the farm.
PMID- 9649873
TI - Comparison of sex-linked dwarf genes in chickens from two sources when
introgressed into unrelated genetic backgrounds.
AB - 1. Sex-linked dwarfing genes from 2 broiler stock origins (EU and US) were each
introgressed into 2 White Leghorn populations that had been divergently selected
for antibody response to sheep erythrocytes. 2. When the resulting backcrossed
populations were 87.5% of their respective. White Leghorn line, non-dwarf pullets
were assessed for body weights, shank lengths, immunoresponsiveness, age and body
weight at sexual maturity, egg production, average egg weight, and duration of
fertility. For measurements where there were no differences between non-dwarf
pullets from the 2 origins of the dwarfing genes, then the dwarf pullets (which
were full sisters to the non-dwarfs) were compared. 3. Shank length at 8 weeks of
age and mature (24-week) body weights were higher for dwarf pullets from EU than
US dwarf origin. Immune response and several egg production traits were higher
for dwarf pullets from the high antibody backcross than from those of the low
antibody backcross. 4. There were few differences in expression of the dwarfing
genes from 2 origins in the unrelated backcross populations used in this study.
Also each of the dwarfing genes, when introgressed into different genomic
backgrounds, was not discernibly different in its expression in terms of antibody
response or egg production characteristics.
PMID- 9649874
TI - Nuclear magnetic resonance imaging as a tool to estimate the mass of the
Pectoralis muscle of chickens in vivo.
AB - 1. Nuclear magnetic resonance imaging (MRI) was used to assess the advantages of
the technique in determining the size (volume) and shape of the Pectoralis muscle
(Pectoralis major and minor) in broiler chickens, non-invasively and in vivo. 2.
The imaging was performed using a Spectroscopy Imaging System 2.0 Tesla/31 cm
bore imaging spectrometer. Three-dimensional reconstruction of transverse images
was used to estimate the size of the Pectoralis muscle of chickens ranging in
body weight from 362 to 1643 g. 3. Regression analysis resulted in R2 values of
0.92 and 0.99 for the relationship between Pectoralis muscle weight, body weight
and muscle volume, respectively. 4. It is concluded that MRI and 3-dimensional
image reconstruction may be used to estimate the Pectoralis muscle size and
shape. This may be readily extended to monitor the influence of various factors
on the growth and development of specific organs and tissues in the body.
PMID- 9649875
TI - Organic matrix morphology and distribution in the palisade layer of eggshells
sampled at selected periods during lay.
AB - 1. 1 cm2 pieces of eggshells from a commercial battery flock were plasma etched
to remove the outer shell membranes. 2. They were decalcified using EDTA (200
g/l, pH 6.9 to 7.0) in paraformaldehyde (20 g/l) and 25% gluteraldehyde (20 ml in
0.98 l) in phosphate buffer, then prepared for light and transmission electron
microscopy. 3. Light microscopy revealed a differential distribution of matrix
material within all 3 regions of the palisade layer at the beginning of lay. 4.
Transmission electron microscopy revealed a more even distribution of matrix at
the beginning of lay, although morphological differences were observed. At the
end of lay all 3 regions showed an increase in % matrix and vesicles/10 cm2 of
micrograph compared to the middle and beginning of lay periods. 5. It is
hypothesised that matrix vesicles are involved in the regulation of the
physiochemical environment within the forming eggshell and that the decline in
shell quality associated with the end of lay is related to a concomitant change
in matrix quality.
PMID- 9649876
TI - Antimicrobial efficacy of AvGard carcase wash under industrial processing
conditions.
AB - 1. The efficacy of the AvGard Trisodium Phosphate (TSP) immersion carcase wash
process was evaluated during 5 industrial trials against Salmonella,
Enterobacteriaceae, thermotolerant coliforms and total aerobic count. The effect
against Pseudomonas was also studied in the first 3 trials. 2. Dramatic
reductions in Salmonella incidence were seen using a whole carcase rinse method.
In 4 of the 5 trial sites, only one positive sample was found after AvGard
treatment (average 0.5% incidence), in spite of an average control incidence of
57.7%. In the 5th site, a water-chilled broiler plant, an average control
incidence of 74.0% was reduced to 9.4% after AvGard treatment. 3. In the latter
case, Most Probable Number (MPN) analyses were performed on some of the
Salmonella positive samples taken from the control and post-treatment series; the
average MPN count per carcase on controls was 115, whereas for AvGard treated
birds the figure was only 0.6 per carcase, a greater than 2 log reduction. 4. In
addition, AvGard treatment gave average log reductions for all trials of:
Enterobacteriaceae; 2.5 log; Coliforms; 2.7 log, and Total Aerobic Count; 1.1
log, leading to carcases substantially free of Gram negative pathogens. 5.
Pseudomonas was reduced by an average of 1.7 log in the first 3 trials,
dramatically reducing the carcase loading of this important spoilage organism.
PMID- 9649877
TI - Effect of dietary administration of oil extracts from rosemary and sage on lipid
oxidation in broiler meat.
AB - 1. Oxidation of meat and membrane from broilers fed on a diet containing 500
mg/kg rosemary and sage extracts was compared to meat and membrane oxidation from
broilers receiving a control diet (not enriched with antioxidants) and a diet
enriched in alpha-tocopheryl acetate (200 mg/kg). 2. After 9 d of refrigerated
storage, thiobarbituric acid reactive substances of white meat from broilers fed
on the control and the alpha-tocopheryl acetate-enriched diets were 0.51 and 0.25
mg malonaldehyde/kg meat, respectively. Values for meat from broilers fed on the
diets containing the rosemary and sage extracts were in the range 0.30 to 0.35 mg
malonaldehyde/kg meat, significantly lower than those from birds fed on the
control diet. A similar trend was observed in the dark meat but differences were
not significant at 9 d of storage. Similar trends were observed in raw samples
stored at -20 degrees C for up to 4 months and in samples cooked at 70 degrees C
and kept stored under refrigeration for up to 4 d. 3. The meat from broilers fed
on the diet containing spice extracts had smaller concentrations of total
cholesterol oxidation products (COPS) than meat from the control group (P <
0.05). Supplemental alpha-tocopheryl acetate reduced the COPS concentrations to a
greater extent than did spice extracts (P < 0.05). 4. A similar trend was
observed in microsomal fraction isolates, in which the rate of
metmyoglobin/hydrogen peroxide-catalysed lipid peroxidation was lower in animals
receiving spice extracts than in those fed on the basal diet.
PMID- 9649878
TI - Decreasing profile of residual sulphaquinoxaline in eggs.
AB - 1. Sulphaquinoxaline (SQ) was added to the diet of laying hens at 200 mg/kg for 7
successive days. Contents (mg/kg) of SQ in albumen and egg yolk of eggs laid
after drug withdrawal were determined by high pressure liquid chromatography
(HPLC). The contents in the whole egg were calculated taking into consideration
the respective weights of albumen and egg yolk. 2. A time-lag in the initiation
of decrease of SQ from eggs after the withdrawal of dietary SQ was observed. 3.
The decreasing pattern from whole egg could be well described by the following
equation with a time-lag of 1.0 d, y = 2.07 e-0.5620(t-1.0), where y is the SQ
content in whole egg, t is time (d) after the withdrawal of dietary SQ and a
constant of 2.07 is the SQ content in whole egg laid at the withdrawal. 4.
Biological half-life of SQ in the whole egg was estimated to be 1.23 d. 5. From
the above equation, SQ residue of whole egg laid at 9th d after withdrawal will
be below the detection limit of 0.01 mg/kg.
PMID- 9649879
TI - Comparison of the utilisation of palm kernel meal, brewers' dried grains and
maize offal by broiler chicks.
AB - 1. Palm kernel meal (PKM), brewers dried grains (BDG) and maize offal (MO) were
included in broiler diets, each at 100, 150 or 200 g/kg; the diets were fed up to
35 d of age. 2. Overall food intake and weight gain decreased in the order BDG,
PKM and MO. There were, however, significant interactions between the test
ingredients and dietary concentrations in all the growth responses. Food intakes
increased with the dietary concentrations of each test ingredient, but the
increase was greater for BDG than PKM or MO. For weight gain, at 100 g/kg, the
final body weights of the chicks fed on the diets with BDG and MO were similar,
and those of chicks fed on the diet with PKM slightly lower. However, at 200
g/kg, growth rate of chicks fed on the BDG and PKM diets were similar while those
of chicks fed on the MO diet was 7% lower. Efficiency of food utilisation was
similar at 100 g/kg for all the ingredients and decreased as their concentrations
increased; however, the decrease was considerably less for the PKM than for the
MO and BDG diets. 3. Broilers fed on the BDG-based diets voided most excreta
followed by those fed on the PKM and MO diets; excreta water content was highest
from birds fed on the MO diets followed by the PKM and BDG diets. Apparent
retention of dry matter was similar with all the test ingredients, but it
decreased only significantly at 200 g/kg dietary concentration. The rate of
passage was faster with the PKM diets followed by the MO and BDG diets; it was
increased at 200 g/kg dietary concentration of the test ingredients.
PMID- 9649880
TI - Influence of dietary protein and sex on walking ability and bone parameters of
broilers.
AB - 1. The study was conducted to investigate the effect of dietary protein on the
walking ability and bone parameters of broilers reared under summer temperatures
which ranged from 26 degrees to 32 degrees C (+/- 2 degrees C). 2. Three
different dietary protein combinations were used. The diets (per kg) were: low
protein with 205 g crude protein and 12.94 MJ ME, 184 g crude protein and 12.75
MJ ME; medium protein with 219 g crude protein and 12.99 MJ ME, 201 g crude
protein and 12.87 MJ ME; and high protein with 238 g crude protein and 12.99 MJ
ME, 216 g crude protein and 12.96 MJ ME from 0 to 4 and 4 to 7 weeks of age,
respectively. Body weights of birds were recorded and birds' walking ability
(gait scoring) were scored for each bird, according to 3 categories (completely
normal to immobile, at 4 and 7 weeks). Tibia parameters and tibia plateau angles
were also determined at 7 weeks. 3. Birds fed on the low protein were lighter
than those fed on the medium or high protein diets. At 7 weeks, birds with poor
walking ability weighted 149 g less than birds with no walking difficulty. 4.
Bone parameters were not affected by dietary protein, sex or gait score. There
was a significantly positive correlation between bone strength and radiographic
density. Bone strength was also significantly correlated with bone weight and
length.
PMID- 9649881
TI - Effect of supplementing the hen's diet with vitamin A on the accumulation of
vitamins A and E, ascorbic acid and carotenoids in the egg yolk and in the
embryonic liver.
AB - 1. The effect of a range of supplementations of vitamin A to the laying hen on
the concentration of vitamins A, E, ascorbic acid and carotenoids in the maternal
liver, the egg yolk and the embryonic liver were investigated. 2. Four groups of
25 Rhode Island Red hens were fed on standard layer-breeder diets with
concentrations of supplemented vitamin A ranging from 0 to 120 micrograms/g
retinol equivalents from 28 weeks of age. After 3 months, the concentration of
vitamin A in the maternal liver was found to be greatly enhanced in proportion to
the increasing rates of supplementation with the vitamin. However, the
concentration of vitamin E in the maternal liver was markedly reduced by high
dietary contents of vitamin A. 3. The concentration of vitamin A in the yolk of
the hens' eggs was markedly increased by the dietary supplementation. However,
the concentration of both vitamin E and carotenoids in the yolks were
significantly reduced by high dietary contents of vitamin A. 4. The concentration
of vitamin A in the liver of the embryo and the day old chick was greatly
increased by the high concentrations of maternal vitamin A provision. However,
the concentration of vitamin E, carotenoids and ascorbic acid in the
embryonic/neonatal liver were significantly reduced by high contents of vitamin A
in the maternal diet. 5. The susceptibility of the embryonic/neonatal liver to
lipid peroxidation was significantly increased as a result of high provisions of
maternal vitamin A. 6. It is concluded that excessive provision of vitamin A to
the laying hen results in an adverse effect on vitamin E, carotenoids and
ascorbic acid in the embryonic/neonatal liver and can compromise the antioxidant
status of the progeny.
PMID- 9649882
TI - Energy and protein metabolism between 3 and 6 weeks of age of male broiler
chickens selected for growth rate or for improved food efficiency.
AB - 1. A new open-circuit respiration unit consisting of 6 respiration chambers, gas
analysis unit and data-acquisition system is briefly described. 2. Energy and
protein metabolism in broiler lines selected for improved food efficiency (FC) or
for growth rate (GL) were measured weekly from 3 to 6 weeks of age. 3. Gross and
apparent metabolisable energy intake per kg W0.75 was on average higher for GL
than for FC chickens without differences in metabolisability. Fed and fasted heat
production per kg W0.75 did not differ between the lines. FC chickens retained
less energy per kg W0.75 than GL chickens. 4. FC chickens deposited much less of
the retained energy as fat than their GL counterparts and also showed greater
protein conversion efficiency. The leaner composition of the body weight gain in
FC chickens was confirmed by the estimated lower fat deposition per kg W0.75 and
by the lower fat: protein ratio.
PMID- 9649883
TI - Quantification of a sperm-egg interaction for estimating the mating efficiency of
broiler breeder flocks.
AB - 1. The frequency distribution of points of sperm hydrolysis (or holes) produced
per unit area of the inner perivitelline layer was examined in samples of
approximately 60 laid eggs, taken on the same day from each of 19 flocks of
broiler breeder hens. 2. The holes counted in samples of perivitelline layer from
eggs varied from 0 to greater than 100; lower numbers being found in eggs from
flocks with lower fertility. 3. The median frequency of holes in the inner
perivitelline layer was strongly correlated (r = 0.92) with the median frequency
of spermatozoa found trapped in the corresponding outer perivitelline layer. 4.
The median frequency of holes in the inner perivitelline layer and of spermatozoa
in the outer perivitelline layer were both strongly correlated (r = 0.80 and
0.77, respectively) with flock fertility. 5. It is suggested that counting
'holes' in the inner perivitelline layer of laid eggs is a more convenient method
for assessing breeding efficiency and predicting flock fertility than counting
spermatozoa trapped in the outer perivitelline layer.
PMID- 9649884
TI - Evaluation of semen from individual male domestic fowl by assessment of sperm:
perivitelline interaction in vitro and in vivo.
AB - 1. Spermatozoa in semen samples from 8 individual male domestic fowls were shown
to have a differential and characteristic ability to hydrolyse holes in the inner
perivitelline layer from laid eggs in an in vitro assay. 2. The number of holes
produced by samples of spermatozoa per unit area of inner perivitelline layer in
vitro was linearly correlated with sperm ATP content (r = 0.85) and motility (r =
0.76). 3. The number of holes formed in the inner perivitelline layer in vitro
was also linearly correlated with the numbers of holes formed in the inner
perivitelline layer of eggs fertilised in vivo, in inseminated hens (r = 0.90);
and was correlated logarithmically with the proportion of fertile eggs laid by
these hens.
PMID- 9649885
TI - Effects of age at onset of production, light regime and dietary calcium on
performance, eggshell traits, duodenal calbindin and cholecalciferol metabolism.
AB - 1. Rate of production and shell thickness (ST) decreased, while body weight (BW),
egg weight (EW) and percentage breakage increased progressively with age. Shell
weight (SW) increased until 8 to 13 months of age and then decreased. 2. Early
onset of production resulted in lower BW and EW at the onset of production, and
lower pooled averages of BW, EW, SW and ST, as compared with late or medial onset
of production. In 4 out of 5 trials, early onset did not result in the production
of more eggs during the laying period. 3. Early onset of production is associated
with physiological Ca deficiency as indicated by increases in kidney-1
hydroxylase and duodenal calbindin in early layers as compared with late layers.
Early layers exhibited a more severe reduction in shell quality as the result of
Ca deficiency as compared with late layers. 4. Feeding pullets with a prelaying
diet containing 3.9% Ca did not affect unequivocally the performance or shell
quality during the whole productive period, whether the birds started to lay
early or late. The dietary treatment did not cause renal damage, as indicated by
morphological examination and by plasma calcium and uric acid concentration.
PMID- 9649886
TI - Comparative development of the ovary and production, fertility and hatchability
of eggs from traditional turkeys and a contemporary male-line fed ad libitum or
restricted.
AB - 1. Ovarian function was assessed at first egg and at 44 and 54 weeks of age in
traditional turkeys and in a male-line fed ad libitum or restricted to 0.5 of ad
libitum during rearing. Egg production was recorded daily and fertility and
hatchability were determined at 2 ages. 2. Age at sexual maturity did not differ
between the 3 treatments. 3. The number of follicles at first egg in the male
line averaged 16.3 compared with 8.9 in traditional turkeys. Food restriction in
the male line decreased the number of yellow follicles to 14.6 at first egg and
restricted birds were largely in a non-reproductive state from 44 to 54 weeks of
age. 4. The total number of recorded ovipositions to 54 weeks of age in male line
fed ad libitum or restricted and traditional turkeys respectively were 40.1, 25.2
and 70.7; comparable productions of normal shelled eggs were 28, 20 and 66.3. 5.
There were no differences between treatments in fertility after a single
insemination at 2 different ages. Hatch of fertiles after the first inseminations
were 71.4, 45.5 and 90.3 respectively for male line fed ad libitum or restricted
and traditional turkeys.
PMID- 9649887
TI - Establishing a medical research agenda for child sexual abuse. Historical
perspective and executive summary.
PMID- 9649888
TI - It's time to broaden the agenda.
PMID- 9649889
TI - Epidemiology of sexual abuse of children: old problems, new directions.
AB - Over the last 2 decades, the science of epidemiology has made important
contributions to the understanding of sexual abuse of children. Well-designed
epidemiological studies conducted during the next two decades should help refine
our knowledge of the frequency of the problem, as well as further our
understanding of risk factors and consequences.
PMID- 9649890
TI - Prevalence, risk, sensitivity, and specificity: a commentary on the epidemiology
of child sexual abuse and the development of a research agenda.
PMID- 9649891
TI - Triage and referrals for child sexual abuse medical examinations from the
sociolegal system.
PMID- 9649892
TI - Triage and referrals for child sexual abuse medical examinations: which children
are likely to have positive medical findings?
PMID- 9649893
TI - Behavioral manifestations of child sexual abuse.
PMID- 9649894
TI - Medical consequences of child sexual abuse.
PMID- 9649895
TI - Technical conduct of the child sexual abuse medical examination.
PMID- 9649896
TI - Further technical considerations regarding conducting and documenting the child
sexual abuse medical examination.
PMID- 9649897
TI - Emotional impact of the medical examination for child sexual abuse.
PMID- 9649898
TI - Children's responses to the medical evaluation for child sexual abuse.
PMID- 9649899
TI - Normal anogenital anatomy.
PMID- 9649900
TI - The appearance of acute, healing, and healed anogenital trauma.
PMID- 9649901
TI - The transmissibility of sexually transmitted diseases in sexually abused
children.
PMID- 9649902
TI - Impact of child sexual abuse medical examinations on the dependency and criminal
systems.
PMID- 9649904
TI - Quantitative digital evaluation of myocardial exercise thallium-201 single-photon
emission tomography in post-menopausal women.
AB - Quantitative computerized analysis of data from myocardial thallium-201 (201Tl)
single-photon emission tomography (SPET) may improve the diagnostic accuracy of
coronary heart disease. The reference ranges for post-menopausal women are,
however, limited and obtained mainly from patients. To compare reference values
from healthy post-menopausal women and to improve the quantitative analysis, 20
women (10 patients with coronary heart disease and previous infarction and 10 age
matched healthy volunteers) were examined immediately post exercise and after a
delay. A nine-segment 'bull's-eye' model was used for analysis. At visual
evaluation, reproducibility was high (93%), no false-positive results were
obtained and in 70% of the patients the SPET was interpreted as abnormal. Using
reported reference values for quantitative analysis, all the healthy women had an
abnormal result. New reference values based on three different methods of
'normalization' were calculated: the relative activity of segment 3 set to 100%,
the segment with the highest activity set to 100% and a least-squares method.
They all differed significantly from those that had previously been reported. The
frequencies of agreement between visual and quantitative analysis were 84-92% and
were highest when segment 3 was used as a reference, but in this case only 40% of
the patients with coronary heart disease had an abnormal SPET. Using the least
squares method for handling digital information, the SD of the normal values
decreased and 90% of the patients with coronary heart disease were accurately
diagnosed. These results provide quantitative digital reference values for
healthy post-menopausal women. They verify that quantitative analysis is in
diagnostic agreement with visual evaluation, stress the need for local
verification of reference ranges and suggest a least-square normalization method
for the analysis.
PMID- 9649905
TI - Electrocardiographic changes during prolonged coronary artery occlusion in man:
comparison of standard and high-frequency recordings.
AB - Detection of acute myocardial ischaemia using electrocardiographic methods is
generally based on assessment of the ST segments in the standard 12-lead
electrocardiogram (ECG). Several studies have also shown changes in high
frequency QRS components during acute ischaemia. The purpose of the present study
was to determine the changes in high-frequency QRS components during prolonged
percutaneous transluminal coronary angioplasty (PTCA) and to compare these
changes with ST-segment deviations in the standard 12-lead ECG. The study
population consisted of 19 patients receiving prolonged PTCA. Standard and high
resolution signal-averaged ECGs were recorded before and during balloon
inflation. The high-resolution recordings were performed using bipolar X, Y and Z
leads. The QRS complexes in the high-resolution signal-averaged ECGs were
analysed within a bandwidth of 150-250 Hz. During inflation, significant
reductions in high-frequency QRS components were observed (12-72%). Changes in
the high-frequency QRS components were seen in four of the patients without ST
segments deviation in the standard ECG. The correlation between the ST-segment
deviation and the reduction in high-frequency QRS components was weak (r = 0.27).
Acute coronary artery occlusion produces changes in high-frequency QRS
components, even in the absence of ST-segment deviation in the standard ECG.
Further studies need to be carried out to evaluate whether analysis of high
frequency QRS components could provide a method for detecting myocardial
ischaemia and give additional information to that available in the ST segment in
the standard ECG.
PMID- 9649906
TI - Poor reproducibility of exercise test in assessment of claudication.
AB - To assess reproducibility of the exercise test in intermittent claudication, a
prospective, comparative, randomized study was undertaken. Ten patients with
stable intermittent claudication of ischaemic origin were exercised on a flat
surface (0-Ex), with 12% steady inclination (12-Ex) and with progressively
increasing inclination (p-Ex) in a random order during three different sessions.
The ankle-brachial index (ABI) at rest and after exercise (rABI, exABI), initial
and maximum walking distance (IWD, MWD) and metabolic equivalent (MET) were
obtained as the main outcome measures. The results were analysed using
intraindividual coefficients of variation (CVs) and standard deviations (SDs).
The ABI values of the worst extremity were used in evaluation of results.
Reproducibility of the exercise ABI appeared to be good, especially during
progressively increasing exercise, the mean CV being 9 +/- 5%. The best mean CV
was observed during p-Ex (16% +/- 14%) for maximum walking distance. The mean CV
for initial walking distances ranged from 30% to 54%. Treadmill exercise testing
to measure walking distances is highly inaccurate and the value of exercise on
the flat treadmill should be questioned. Graded exercise appeared to be the most
reproducible in this respect. The ABI after exercise, however, was a reliable
single parameter when assessing arterial insufficiency causing decreased walking
capacity.
PMID- 9649907
TI - Reduced left ventricular relaxation velocity after acute myocardial infarction.
AB - Diastolic left ventricular function is usually described using Doppler recording
of the early to atrial (E/A) ratio. However, because of pseudonormalization in
patients with moderately impaired diastolic function, the E/A ratio does not
allow a meaningful comparison between a group of patients with varying degrees of
dysfunction, e.g. after acute myocardial infarction (AMI), and a group of healthy
control subjects. In this study, diastolic function was assessed using the E/A
ratio, deceleration time of early mitral inflow and maximal longitudinal
relaxation velocity. The relaxation velocity was measured using echocardiographic
M-mode recording of mitral annulus motion. Mitral annulus motion was recorded in
four- and two-chamber views. Relaxation velocities were measured in the septal,
lateral, anterior and posterior parts of the mitral annulus and the mean value
(RVm) was calculated. Twenty-two consecutive patients were investigated 3-21 days
after first transmural AMI. Twenty-two healthy subjects of similar age served as
a control group. The group of patients with AMI had an RVm of 40.9 +/- 15.4 mm s
1 compared with 68.5 +/- 12.4 mm s-1 in the control group (P < 0.0001). In
contrast, the E/A ratio, deceleration time and heart rate did not differ
significantly between the two groups. The results suggest that maximal
longitudinal relaxation velocity is a simple and appropriate measure of diastolic
function in patients with transmural AMI.
PMID- 9649908
TI - High blood pressure and muscle morphology/metabolism--causal relationship or only
associated factors?
AB - As muscle tissue constitutes a main target organ for glucose metabolism and is
responsible for the development of insulin resistance, it seems plausible to
elucidate the relationship between blood pressure and muscle morphology and
metabolism. The association between blood pressure and capillarization/morphology
of the vastus lateralis muscle and metabolic variables was evaluated in 24
perimenopausal obese women [body mass index (BMI) 34.9 +/- 1.1; waist-hip ratio
(WHR) 0.90 +/- 0.02]. The muscle enzyme activity of lipoprotein lipase (LPL),
citrate synthase and glycogen synthase was determined. There was a significant
negative correlation between the percentage of type I fibres and relative fibre
area of type I on the one hand and systolic and diastolic blood pressure on the
other. There was a negative correlation between the capillary density (i.e.
number of capillaries/muscle fibre) and a positive correlation between the
diffusion distance (fibre area supplied by one capillary) and diastolic blood
pressure. The activities of LPL and citrate synthase were positively correlated
with the percentage of type I and negatively correlated with the percentage of
type II muscle fibres. The activity of LPL was also negatively correlated with
plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was
positively correlated with the percentage of type II muscle fibres. In stepwise
multiple regression analyses, 20-30% of the variation in systolic and diastolic
blood pressure could be explained by the variables of muscle fibre distribution.
Excluding muscle morphological variables from the regression model, the insulin/C
peptide ratio accounted for 13% of the variation in systolic and diastolic blood
pressure. The results of the study show the close association between muscle
morphology and blood pressure. It remains to be elucidated whether this
association indicates a causal relationship.
PMID- 9649909
TI - Office and laboratory blood pressures as predictors of daily blood pressure level
in normotensive subjects and borderline and mild hypertensive subjects.
AB - A series of standardized laboratory tests [10 min sitting and supine, 9 min
standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)]
were performed during intra-arterial blood pressure (BP) recording in 97 healthy
unmedicated men, initially classified as normotensive (NT, n = 34), borderline
hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office
blood pressure (OBP) measurements. After testing, a 24-h intra-arterial
ambulatory BP (IABP) recording was obtained while subjects performed their normal
activities. Day and night periods were analysed as well as 24-h averages for
systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple
linear regressions. In normotensive subjects, the supine SBP predicted IABP
measurements best (r range 0.39-0.69, P < 0.05-0.001). In multiple regression,
supine SBP explained 49% of 24-h SBP variance (F = 12.4, P = 0.001). For BHT,
supine SBP was also the best predictor (r range 0.09-0.64, P NS to P < 0.001),
and it explained 37% of 24-h SBP variance (F = 15.6, P = 0.0005). In HT, ERG DBP
correlated best with IABP (r range 0.52-0.75, P < 0.01-0.001). ERG SBP explained
49% of 24-h SBP (F = 31.0, P = 0.0000) and ERG DBP explained 56% of 24-h DBP (F =
35.4, P = 0.0000) variance. Laboratory BP correlations were generally better with
day than with night measurements. OSBP correlated moderately well with IABP in
NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but
not significantly in BHT. In conclusion, OBP is less closely related to IABP than
laboratory BP, but even laboratory BP generally explains less than 50% of IABP
variance. Stressors such as exercise are useful only in HT. For BHT, the
prediction of IABP with laboratory measures was even weaker than in other groups,
and thus ambulatory measurements cannot be replaced by short-duration laboratory
measurements and stress tests.
PMID- 9649910
TI - Reproducibility of oximetry with a static charge-sensitive bed in evaluation of
obstructive sleep apnoea.
AB - The reproducibility of overnight polygraphic recording with oximetry, the use of
a static charge-sensitive bed (SCSB), thermistors and a body position sensor was
assessed in diagnosing obstructive sleep apnoea syndrome (OSAS). Forty-six
patients with a clinical suspicion of OSAS underwent a repeat recording. No
treatment for OSAS and no change in patient characteristics was allowed between
duplicate nights. Between repeated recordings significant correlations were found
for ODI4, time spent at SaO2 < 90% and the mean nadir SaO2. Good agreement was
found in concordance of classification of ODI4, time spent at SaO2 < 90% and body
movements. The combination of oximetry, thermistors, SCSB and body position
sensor has a good reproducibility as an affordable screening method in the
evaluation of OSAS.
PMID- 9649911
TI - Breathing efficiency during inspiratory threshold loading in patients with
chronic obstructive pulmonary disease.
AB - Patients with chronic obstructive pulmonary disease (COPD) demonstrate an
increased oxygen cost of breathing. It is as yet unclear whether this is related
to a decreased breathing efficiency. The aim of the present study was to compare
breathing efficiency in 16 patients with COPD (11 men, five women) and 16 healthy
elderly subjects (seven men, nine women), and to investigate a possible
relationship between breathing efficiency and resting energy expenditure (REE).
REE was measured using a ventilated hood system. Breathing efficiency was
assessed by measuring oxygen consumption (V'O2), mean inspiratory mouth pressure
(MIP) and flow during breathing at rest and subsequently during breathing against
an inspiratory threshold (40% of maximal inspiratory pressure). During loaded
breathing there was a significant increase in V'O2, MIP, and external work of
breathing compared with unloaded breathing in both groups. As intended,
ventilation did not increase significantly during the breathing efficiency test
in the patients with COPD. The breathing efficiency (median, range) of the
patients with COPD was similar (3.7%, 1.4-8.7%) to that of the healthy elderly
subjects (3.2%, 1.7-8.3%). Breathing efficiency was not correlated with REE in
either group. In the present study, in which dynamic hyperinflation was probably
prevented, no difference in breathing efficiency was found between healthy
elderly subjects and COPD patients when breathing against an external inspiratory
threshold. Furthermore, breathing efficiency was not related to REE in both
groups.
PMID- 9649912
TI - Divergent cardiac response to exercise in essential hypertension vs. normotension
and the effect of enalapril.
AB - The aims of this study were to examine (1) the cardiac response to exercise in
essential hypertension and (2) the effect of long-term enalapril treatment on
cardiac reserve. Ten normotensive control subjects and 15 patients with moderate,
essential hypertension underwent radionuclide ventriculography during graded,
supine exercise (0 W-50 W-100 W). The hypertensive patients were studied during
monotherapy using hydrochlorothiazide and 3 and 12 months after supplementation
with enalapril 10-40 mg o.d. During exercise, the control subjects demonstrated a
17% increase in left ventricular ejection fraction (LVEF) mediated by a 30%
decrease in end-systolic volume, a small increase in stroke volume and a minor
biphasic (increase-decrease) change in end-diastolic volume. In the hypertensive
patients, both the end-diastolic and the end-systolic volume increased
substantially with no increase in LVEF, although stroke volume increased by 33%.
Long-term therapy with enalapril induced only a minor change towards a more
normal pattern of cardiac response to exercise. The hypertensive patients
increased their stroke volume during exercise by recruiting preload reserve
instead of increasing contractility. Long-term treatment with enalapril had
little, if any, effect on this abnormal cardiac response.
PMID- 9649913
TI - Oral contraception and other factors in relation to hospital referral for
fracture. Findings in a large cohort study.
AB - There is good evidence that estrogens and progestogens have an important effect
on bone metabolism. This article explores the relationship between oral
contraceptive (OC) use and fractures occurring at various sites among the 17,032
participants in the Oxford-Family Planning Association contraceptive study, which
now includes information accumulated during 310,000 woman-years of observation
between 1968 and 1994. In total, 1308 women suffered at least one fracture during
the follow-up period, which was largely confined to premenopausal years. When all
fractures were combined, there was a modest, but highly significant trend (p <
0.001) of increasing risk with total duration of oral contraceptive use. In
addition, there was statistically significant heterogeneity (p < 0.01) when
overall fracture rates were examined in relation to recency of oral contraceptive
use during the premenopausal lifespan. The highest relative risk (1.3, 95% CI 1.1
1.5) was for current or recent oral contraceptive users; however, viewed as a
whole, no clear pattern of risk was apparent. Examination of the data for
individual fracture sites (including the lower end of the radius/ulna) did not
provide any evidence of a protective effect of oral contraceptive use. These
results are closely similar to those reported from the Royal College of General
Practitioners Oral Contraception Study in 1993.
PMID- 9649914
TI - Depressive symptoms and Depo-Provera.
AB - Women enrolled in a multicenter prospective study were evaluated to identify any
possible relationship between depressive symptoms and the use of contraceptives.
Women choosing Depo-Provera (n = 495) were evaluated before starting these
contraceptives and were reinterviewed 1 year later. Women who continued the
method had lower depressive symptom scores at baseline than did the women who
discontinued the method or who were lost to follow-up. Among the continuing Depo
Provera users, the depressive symptom scores improved slightly at 1 year (7.4 vs
6.7). Those subjects with the highest (i.e., worst) scores at enrollment
demonstrated improved scores at follow-up.
PMID- 9649915
TI - Depressive symptoms and Norplant contraceptive implants.
AB - Women enrolled in a multicenter prospective study were evaluated to identify any
possible relationship between depressive symptoms and the use of contraceptive
implants. Women choosing Norplant implants (n = 910) were evaluated before
starting this contraceptive and were reinterviewed at 6 months and 2 years. Women
who continued the method had lower depressive symptom scores before initiating
Norplant implants than did the women who discontinued the method or who were lost
to follow up. Among the continuing Norplant implant users, the mean scores were
similar before starting Norplant and at 6 months (7.9 vs 7.7). The strongest
overall predictor of the depressive symptom score was relationship satisfaction.
At 24 months, the subgroup of continuing users with decreased relationship
satisfaction had an increase in depressive symptom score, but those with stable
or improved relationships had stable depressive symptom scores. The subjects with
the highest (i.e., worst) scores at enrollment demonstrated improved scores
during follow-up. These results are reassuring for women who are concerned that
Norplant use may adversely affect their mood.
PMID- 9649916
TI - Oral contraceptive use before and after the latest pill scare in The Netherlands.
Changes in oral contraceptive use and how users change.
AB - In October 1995, a "pill scare" developed in Europe. In the Netherlands, the
recommendations given were 1) to not alarm women without risk for deep vein
thrombosis (DVT), and 2) to be reserved in prescribing third generation oral
contraceptives (OC) for young women who were beginning OC use. To determine
whether there is a change in the prescription of third generation OC after the
latest pill scare, prescription data from 1/10/94 to 1/10/96, covering a
population of +/- 120,000 persons, were studied with respect to OC use before and
after the pill scare. Trend analyses revealed a significant decline in third
generation compared with total OC prescribing only in the youngest age category
(p = 0.0034). Further, switch behavior was studied. Switches from third to second
generation OC were more prevalent after the pill scare than before (odds ratio =
2.63; 95% confidence interval 1.84-3.75) and switches from second to third
generation OC were significantly less prevalent after the pill scare. This
indicates that Dutch prescribers have reacted to the pill scare in the way that
the government recommended.
PMID- 9649917
TI - Perforations with intrauterine devices. Report from a Swedish survey.
AB - This survey comprised 50 consecutive perforations occurring with intrauterine
devices (IUD) reported to the National Patient Insurance Scheme Register during
1990 to 1993. All 50 women were parous and > 20 years of age at the time of IUD
insertion. Forty-two (84%) of the IUD were inserted by a midwife and eight by a
gynecologist. A total of 45 women (90%) had their IUD inserted < 1 year after a
full-term pregnancy and 31 women (62%) had their IUD inserted < or = 12 weeks
after delivery. Of the 50 women, 27 (54%) reported that they were breastfeeding
at the time of IUD insertion. No particular IUD was overrepresented in relation
to its share on the market. In 31 cases (62%), severe pain at insertion and
during the first 24 h was recorded. In 14 women (28%), the perforation was
diagnosed early (i.e., within 1 month of insertion) and in 36 women (72%), the
perforation was diagnosed > 1 month after insertion. Lower abdominal pain was the
most frequent symptom at early diagnosis but in two cases, the main symptom was
heavy bleeding. Among the 36 women in whom the perforation was discovered more
than 1 month after insertion, the diagnosis was made when an unexpected pregnancy
occurred in 20 women (56%). In 15 cases, the IUD strings were not visible during
pelvic examination at a routine check-up, which led to efforts to locate the IUD.
Thirty-two women (64%) underwent laparotomy for removal. We conclude that
lactating women seem to be a risk group for perforation and that a national
register of IUD perforations could provide a better means of quality control.
PMID- 9649918
TI - Identification of choriocarcinoma by the hCG beta-to-hCG proportion in patients
with delayed diagnosis caused by contraceptive use.
AB - The use of contraceptives, especially subdermal implants and levonorgestrel
containing intrauterine device (IUD), often cause irregular bleeding. Thus, they
may mask unsuspected choriocarcinoma, which also often presents with abnormal
bleeding. Choriocarcinoma is mostly curable with combination chemotherapy, but
delayed diagnosis can lead to treatment failure. Two cases of choriocarcinoma
with considerable delay in diagnosis, due partly to contraceptive use, are
reported. The proportion of human chorionic gonadotropin-beta (hCG beta) and
total hCG immunoreactivity showed that the proportion of hCG beta was elevated at
presentation in both cases.
PMID- 9649919
TI - Tamoxifen-induced light and electron microscopic changes in the rat testicular
morphology and serum hormonal profile of reproductive hormones.
AB - The effects of oral administration of tamoxifen at doses of 40 and 200
micrograms/kg/day on testicular histology, testicular ultrastructure and serum
hormonal profile were studied. The drug was administered to adult male rats over
a period of 90 days and the effect was assessed at 10-day intervals. The
morphometry, microscopic structures of the testis, including ultrastructure and
daily sperm production rate, were evaluated. The hormone profiles of luteinizing
hormone (LH), follice-stimulating hormone (FSH), testosterone, and estradiol were
studied. The testes from treated animals showed disorganization of tubular
elements with increased intercellular space. At day 50, the changes were
extensive including presence of phagosomes. Morphometric studies showed a
reduction in the spermatid and spermatozoan population (69.3%) with no changes in
tubular diameter. The mean Leydig cell area was significantly lowered at day 50,
at both doses. The daily sperm production rate was reduced as compared with
controls. An array of degenerative changes were revealed by ultrastructural
studies. The changes were extensive at day 50 at both doses. The characteristic
features were lost in most of the cells with phagolysosomes becoming abundant.
The cytoplasm of the cells was dense with poorly defined cytoplasmic organelles.
Circulating LH levels were not modified at the 40 micrograms/kg/day dose but at
200 micrograms/kg/day, LH levels were significantly decreased. Initial transitory
rise in FSH was seen with both doses. Both doses of tamoxifen decreased
testosterone levels. Changes in the circulating estradiol levels were
inconsistent, and no apparent relationship between dose and days of treatment was
observed. Thus, this study supports our thesis of tamoxifen as a potential male
contraceptive agent.
PMID- 9649920
TI - Long-term sequelae of tolnidamine on male reproduction and general body
metabolism in rabbits.
AB - The long-term effects of tolnidamine on male reproduction and general body
metabolism were studied in rabbits (Oryctolagus cuniculus). The study was divided
into three groups of 10 animals each. The first group (A) received vehicle alone
to serve as controls. The second and third groups (B and C) of animals were
administered tolnidamine orally at 50 mg/kg body weight/week and 50 mg/kg body
weight/day, respectively, for a period of 150 days. The animals of group B
exhibited a sperm density of 23.60 million/mL +/- 4.87 million/mL (vs 453.00
million/mL +/- 65.30 million/mL in group A) after 150 days of treatment. In group
C, all animals were azoospermic after 135 days of treatment. A reversible
impairment of sperm motility, vitality and morphology was noticed. Semen weight,
volume, color, pH, libido, and circulatory levels of testosterone remained
unchanged. In group B animals, sperm density did not return to control levels
even at 150 days after cessation of treatment (37.40 million/mL +/- 4.46
million/mL, vs 380.00 +/- 40.80 million/mL in group A). However, spermatozoa
reappeared in animals treated daily (group C) after 30 days of recovery but
remained < 5 million/mL during the entire recovery period. A reversible,
significant depletion was recorded in seminal glycerylphosphorylcholine (GPC)
levels. Fertility was unimpaired in group B animals when compared with those in
group A. In group C, fertility was reduced to zero after 150 days of treatment
and at 90 days and 150 days after cessation of treatment. No significant
alterations were observed in other semen biochemical, hematologic, or blood/serum
biochemical parameters with either dose regimen. It is concluded that tolnidamine
administration induced dose dependent, irreversible inhibition of sperm
production without altering general body metabolism in male rabbits.
PMID- 9649921
TI - c-fos protein expression in apoptotic rat spermatocytes induced by gossypol.
AB - Proto-oncogene products such as c-fos protein with a molecular weight of 62 kDa
have been identified in rat spermatocytes. In this study, cellular levels of c
fos proteins in spermatocyte, either with or without gossypol exposure, were
quantitatively detected by Western immunoblot and a computer-controlled Spot
denso-program with an IS-1000 Digital Imaging System. Within 0.5-3.5 h (an
average of 2 h) of the addition of gossypol, levels of c-fos proteins fell
dramatically. The reduction in c-fos proteins occurred 6 h before the apoptosis
of spermatocytes in the presence of gossypol. Four hours after exposure to
gossypol, the c-fos protein content was overexpressed. The period of c-fos up
regulation lasted for approximately 8 h. The increase in c-fos protein coincided
with a high rate of apoptotic cell death. Morphologic structure of the dying cell
was revealed by electron microscopy. These results suggest that spermatocyte
apoptosis induced by gossypol correlates with biphasic c-fos protein-mediated
apoptosis.
PMID- 9649922
TI - Growth response of human coronary smooth muscle cells to angiotensin II and
influence of angiotensin AT1 receptor blockade.
AB - BACKGROUND: The renin-angiotensin system has been implicated in the development
of vascular wall thickening in cardiovascular disease, through the growth
promoting actions of the vasoconstrictive agent, angiotensin II, on vascular
smooth muscle cells. OBJECTIVE: To investigate the effect of angiotensin II on
growth of human coronary artery smooth muscle cells (cSMCs) in culture, and to
identify the angiotensin receptor(s) mediating such a response. METHODS: Human
cSMCs were isolated from coronary arteries of recipient hearts obtained during
transplantation, and characterized by immunohistochemistry. The effect of
angiotensin II on protein synthesis by cSMCs was measured by [3H]leucine
incorporation and protein concentration assays. Human cSMC proliferation was
assessed by [3H]thymidine incorporation assay and cell count. Reverse
transcriptase polymerase chain reaction (RT-PCR) was used to detect angiotensin
receptor expression. Transient increases in intracellular calcium concentration
in cSMCs in response to angiotensin II stimulation were visualized under fura-2
fluorescence microscopy. RESULTS: Angiotensin II (1 nmol/l-10 mumol/l) stimulated
protein synthesis in cSMCs (maximum 24 +/- 2% increase in incorporation of
[3H]leucine over 48 h; n = 4, P < 0.01). An increase in cellular protein content
was also measured. However, angiotensin II had no effect on proliferation of
quiescent cSMCs. The increased protein synthesis was completely inhibited by
pretreatment with the angiotensin AT1 receptor antagonist, losartan, but not the
AT2 receptor antagonist, PD123319. Expression of the angiotensin AT1 receptor
subtype was detected in cSMCs by RT-PCR. Angiotensin II stimulation of cells
triggered transient increases in intracellular calcium concentration, which were
abolished by losartan, but were insensitive to PD123319 and pertussis toxin.
CONCLUSIONS: The results of this study in human coronary VSMCs indicate that
angiotensin II and the AT1 receptor may be involved in the development of
coronary artery disease in man.
PMID- 9649923
TI - Pathogenetic implications of hyaluronan-induced modification of vascular smooth
muscle cell fibrinolysis in diabetes.
AB - BACKGROUND: Proteolysis, modulated in part by intramural fibrinolytic system
proteins and their inhibitors, appears to influence vascular smooth muscle cell
(SMC) migration and proliferation and remodeling of extracellular matrix (ECM).
Alterations of fibrinolysis in circulating blood and of proteolysis within vessel
walls in experimental animals and patients with diabetes have been associated
with accelerated vascular disease. Hyaluronan, a prominent component of ECM in
normal vessels, is increased in the tunica media of macroscopically normal
arterial vessels from patients with type 2 diabetes. OBJECTIVE: To determine
whether hyaluronan alters the expression of the fibrinolytic system protein,
plasminogen activator inhibitor type-1 (PAI-1), in human vascular SMCs, thereby
potentially accelerating vascular disease in patients with type 2 diabetes.
METHODS: Urokinase-type and tissue-type plasminogen activators (uPA and tPA) and
PAI-1 were assayed in vascular SMC conditioned media and in cell lysates, using
enzyme-linked immunosorbent assay and western blotting. RESULTS: Hyaluronan
increased the 24-h release of PAI-1 into conditioned media in a concentration
dependent and time-dependent manner (1.8-fold compared with control with 1 mg/ml
hyaluronan; n = 9, P < 0.01). Although the accumulation of uPA in conditioned
media tended to increase also, uPA content was reduced in cell lysates (64% of
control with 0.1 mg/ml hyaluronan at 24 h; n = 9, P < 0.01) without any change in
PAI-1. Concentrations of tPA in conditioned media and cell lysates were
unchanged. Digestion of hyaluronan with hyaluronidase (50 turbidity reducing
units (TRU)/ml) or exposure of the smooth muscle cells to antihuman CD44 antibody
(1 microgram/ml) that binds to the hyaluronan cell surface receptor obviated the
effects of hyaluronan. CONCLUSION: Our results indicate that increases in
hyaluronan increase vascular SMC expression of PAI-1, a phenomenon that may alter
the balance between proteolysis and its inhibition in vessels of patients with
type 2 diabetes, thereby contributing to the acceleration of macroangiopathy.
PMID- 9649924
TI - Influence of the culprit lesion on clinical symptoms of coronary artery disease,
with special emphasis on exercise data.
AB - BACKGROUND: Clinical symptoms have been found to correlate only poorly with the
severity of the culprit lesion in coronary artery disease. The purpose of the
present study was to evaluate the influence of the culprit lesion and its change
during exercise on clinical symptoms in patients with this condition. METHODS:
Minimal luminal area was determined using biplane quantitative coronary
angiography in 42 patients (aged 53 +/- 8 years) with coronary artery disease.
Percent diameter stenosis and minimal luminal area and its change during exercise
were assessed in all patients and compared with clinical symptoms judged
according to the functional classification of the New York Heart Association
(NYHA). Coronary dimensions were determined with the patient at rest, during
supine bicycle exercise and after sublingual administration of 1.6 mg glyceryl
trinitrate. RESULTS: Exercise-induced vasoconstriction of the culprit lesion was
found in all patients (-14.0% at 102 W), but there was exercise-induced
vasodilatation in the normal vessel segments (+13.0%). However, only minimal
vasoconstriction was found in groups 1 (NYHA I: -0.5%, NS) and 2 (NYHA II: -4.7%,
NS), but significant constriction in groups 3 (NYHA II-III: -18.0%, P < 0.01) and
4 (NYHA III: -31.4, P < 0.01). Vasodilatation of the normal vessel segments was
similar in the four groups. The observed inverse relationship between exercise
induced changes in minimal luminal area and NYHA classification was stronger than
the relationship between NYHA and minimal luminal area when the patient was at
rest. There was no correlation between glyceryl trinitrate-induced vasodilatation
and NYHA classification. CONCLUSIONS: The more severe the culprit lesion, the
more pronounced the exercise-induced vasoconstriction. This effect of the culprit
lesion was reflected by the clinical symptoms: the greater the exercise-induced
vasoconstriction, the higher the NYHA classification. Thus the anatomy of the
lesion (= severity) and the functional integrity of the endothelium (= exercise
induced vasomotion) are two major determinants of clinical symptoms.
PMID- 9649925
TI - Alterations in collagen subtype III and IV protein in experimental venous bypass
grafting.
AB - OBJECTIVE: To examine changes in collagen III and IV protein during the
development of intimal hyperplasia in experimental vein grafts. METHODS: Sixteen
New Zealand White rabbits underwent reversed, jugular vein, interposition
grafting of the carotid artery. Vessels were harvested 3, 7 or 28 days after
operation and subjected to immunohistochemical examination and gelatinase assays.
RESULTS: In control vein, collagen IV was expressed around adventitial blood
vessels and throughout the endothelium. Compared with its presence in control
veins, collagen IV protein was decreased in the endothelium in all 3-day vein
grafts and undetectable in the endothelium and intima in 7-day vein grafts, but
was present in the endothelium and intimal hyperplasia in 28-day vein grafts. In
contrast, collagen III was absent from the endothelium of control vein and 3-day
vein grafts, was present at low levels in the intima of 7-day vein grafts, but
was absent from the endothelium and intimal hyperplasia in 28-day vein grafts. In
3-day vein grafts, areas of collagen IV loss colocalized to areas of leukocyte
infiltration. Protein extracts from 3-day vein grafts contained a 72 kDa
gelatinase. CONCLUSIONS: The presence and alterations of collagen protein in
veins and vein grafts are subtype specific. Collagen III does not appear to be a
normal component of intimal hyperplasia in vein grafts. The decrease in collagen
IV protein in the endothelium of veins may be a component of the endothelial
changes that follow bypass grafting, mediated by leukocytes, the induction of
gelatinase activity, or both.
PMID- 9649926
TI - QRS complex distortion predicts no reflow after emergency angioplasty in patients
with anterior wall acute myocardial infarction.
AB - BACKGROUND: In patients with acute myocardial infarction, distortion of the
terminal portion of the QRS complex on the electrocardiogram (ECG) at the time of
their admission to hospital is associated with larger final infarct size and
greater mortality. This study assessed the results of emergency coronary
angioplasty in patients with anterior acute myocardial infarction with and
without distortion of the terminal portion of the QRS complex on the admission
ECG. METHODS: We assessed the Thrombolysis in Myocardial Infarction (TIMI) trial
flow grade, resolution of ischemic ECG changes, and clinical outcome after
emergency angioplasty for acute anterior wall myocardial infarction in patients
with (n = 21) and without (n = 21) distortion of the terminal portion of the QRS
complex on the admission ECG. RESULTS: Compared with patients without distortion
of the terminal portion of the QRS complex on the admission ECG, those with
distortion had a significantly lower incidence of TIMI flow grade 3 (52% compared
with 84%, P < 0.05), lower rate of resolution of the ischemic ECG changes (33%
compared with 84%, P < 0.005), and greater rate of mortality during their stay in
hospital despite successful balloon angioplasty (19% compared with 0%, P < 0.05).
CONCLUSIONS: In patients with anterior wall acute myocardial infarction,
distortion of the terminal portion of the QRS complex on the admission ECG
predicts a greater mortality rate and a greater incidence of reflow impairment
after emergency angioplasty.
PMID- 9649927
TI - Protective effect of nisoldipine on dipyridamole-induced myocardial ischemia:
correlation with exercise electrocardiography.
AB - BACKGROUND: Nisoldipine, a dihydropyridine calcium channel blocker with strong
coronary dilatative action, is commonly used in the treatment of myocardial
ischaemia; its beneficial effect on effort angina has been demonstrated by
several previous reports. Infusion of dipyridamole in doses sufficient to provoke
myocardial ischaemia in patients with significant coronary artery disease is used
safely in imaging studies for diagnostic purposes. OBJECTIVE: To evaluate the
potential effect of nisoldipine on dipyridamole-induced ischaemia and to compare
the results with the effect of nisoldipine on exercise-induced ischaemia. METHOD:
Twelve patients (10 men and two women, mean age 62 +/- 8 years) with significant
coronary artery disease (at least 70% lumen reduction in at least one major
coronary vessel) were selected for inclusion in the study. In accordance with the
inclusion criteria, the patients exhibited an ischaemic diagnostic response to a
multistage exercise electrocardiography stress test (> 0.15 mV ST segment
depression compared with the resting electrocardiographic tracing) and to a
dipyridamole-echocardiography test (transient left ventricular dyssynergy of
contraction during infusion of dipyridamole up to 0.84 mg/kg over 10 min), after
3 days' cessation of antianginal treatment. After treatment with oral nisoldipine
(10 mg twice daily) was introduced, the patients repeated the two tests, within
18 days of the first evaluation. RESULTS: The dipyridamole-echocardiography test
was positive for ischaemia in 12 patients who were not receiving nisoldipine and
in eight patients who were receiving the drug (100% and 67% respectively, P <
0.05). In the eight patients who gave positive dipyridamole-echocardiography
tests both with and without treatment, dipyridamole time (time to onset of
dyssynergy during the test) increased from 7.9 +/- 2.9 min to 10.2 +/- 3.1 min (P
< 0.01). In these patients, no significant changes were observed, at ischaemia,
in the severity and extent of induced dyssynergy, evaluated as wall motion score
index (each of 16 left ventricular segments scored from 1 = normal to 4 =
dyskinetic) after treatment (score variations from baseline to ischaemia: 0.20 +/
0.11 without nisoldipine and 0.16 +/- 0.06 with nisoldipine; NS). Variations in
dipyridamole time (arbitrarily considered to be 15 min in the negative
dipyridamole-echocardiography test) were significantly correlated with variations
in exercise time (duration of exercise to exhaustion or diagnostic positive
response on the electrocardiogram): r = 0.75 (P < 0.01). No significant
differences were recorded in rate-pressure product (beats/min x mmHg x 100) at
peak ischaemia between patients who were or were not receiving nisoldipine,
during either the exercise electrocardiography stress test (233 +/- 36 with
nisoldipine and 244 +/- 39 without nisoldipine; NS) or the dipyridamole
echocardiography test (147 +/- 21 with nisoldipine and 133 +/- 30 without
nisoldipine; NS). CONCLUSION: Nisoldipine treatment can protect from dipyridamole
induced ischaemia, being associated with a longer stress time, and completely
preventing the development of ischaemia in some patients. The therapy-induced
changes in ischaemic threshold during the dipyridamole-echocardiography test
correlate with variations in exercise tolerance.
PMID- 9649928
TI - Indobufen compared with aspirin and dipyridamole on graft patency after coronary
artery bypass surgery: results of a combined analysis.
AB - BACKGROUND: Two prospective, randomized, double-blind clinical trials, performed
in the UK and Italy, showed that indobufen, a reversible cyclo-oxygenase
inhibitor, is as effective as, and safer than, a combination of aspirin with
dipyridamole in preventing occlusion of saphenous vein coronary artery bypass
grafts (CABG) 1 year after surgery. OBJECTIVE: To obtain, in a larger patient
population, a more precise estimate of the possible differences in efficacy and
safety between the two treatments. METHODS: We performed a combined analysis of
the results of the two studies, based on the 1-year angiography data, on a total
of 934 patients with 2258 saphenous vein distal anastomoses. RESULTS: Patients in
the UK and Italy had similar baseline clinical characteristics. The analysis
confirmed that there were no significant differences between the two treatment
groups in the proportion of patients with one or more occluded grafts and in the
proportion of occluded distal anastomoses. The combined analysis showed that the
difference in response frequency (indobufen compared with aspirin and
dipyridamole) was close to 0: 2.0% (95% confidence interval (CI) -4.2 to 8.2) in
terms of patients, and 0.8% (95% CI -2.5 to 4.2) in terms of distal anastomoses.
The 1-year incidence of postoperative major cardiovascular events was not
statistically different between the treatment groups (19/694 indobufen compared
with 25/678 aspirin and dipyridamole). CONCLUSIONS: Two multicentre CABG studies
performed in different countries in patients with similar characteristics showed
similar results in terms of graft patency. On the basis of the combined analysis,
the two treatments can reasonably be considered to be equally effective in the
prevention of graft occlusion.
PMID- 9649930
TI - Bibliography. Current world literature.
PMID- 9649929
TI - Warfarin reduces silent cerebral infarction in elderly patients with atrial
fibrillation.
AB - BACKGROUND: Atrial fibrillation is reportedly one of the risk factors of silent
cerebral infarction. The Shiga Atrial Fibrillation Trial was conducted in five
medical centers, to test the hypothesis that warfarin can prevent silent cerebral
infarction in patients with atrial fibrillation. METHODS: Magnetic resonance
images (MRI) were taken at the time of the patient's entry to the study and 1
year later in 15 asymptomatic patients (74 +/- 4 years old) with atrial
fibrillation who were randomly allocated to two treatment groups to receive or
not receive warfarin. The frequency of hyperintensities on T2-weighted axis MRI
was rated using a four-point scale in the periventricular and centrum semiovale
areas. Total silent cerebral infarction scores were calculated at the sum of the
scores on MRI. RESULTS: Silent cerebral infarction was seen in 14 (93%) of the 15
patients with atrial fibrillation and a total of 109 silent cerebral infarction
lesions were detected. The number of hyperintensities in the periventricular and
centrum semiovale areas increased over the 1 year of study (P < 0.01). The
increase in total score over 1 year was less in the warfarin-treated group (1.6
+/- 0.7 compared with 5.4 +/- 0.9, P < 0.05). CONCLUSION: Anticoagulation therapy
can be useful to prevent silent cerebral infarction in neurologically normal
elderly patients with atrial fibrillation.
PMID- 9649931
TI - Pregnancy after breast cancer. The relationship of pregnancy to breast cancer
development and progression.
PMID- 9649932
TI - Essential fatty acids: molecular and cellular basis of their anti-cancer action
and clinical implications.
PMID- 9649933
TI - Small cell lung cancer: current status of new chemotherapeutic agents.
PMID- 9649934
TI - The role of adjuvant chemotherapy in the treatment of adult soft tissue sarcomas.
PMID- 9649935
TI - Soluble and insoluble fiber influences on cancer development.
PMID- 9649936
TI - The role of exercise testing and gas-exchange measurement in the prognostic
assessment of patients with heart failure.
AB - Functional impairment has long been recognized as an important factor in the risk
paradigm among patients with heart disease. In chronic heart failure, this issue
has been even more important in recent years because of the steady growth in the
number of patients awaiting heart transplantation relative to the available pool
of donor hearts. The use of gas-exchange techniques to assess patients with heart
failure has attracted interest because these techniques provide a more precise,
reproducible, objective, and physiologic expression of exercise tolerance.
Numerous studies published in the 1990s demonstrate that maximal oxygen uptake
(peak VO2) is an independent predictor of mortality in patients with heart
failure. Achievement of a peak VO2 that is less than 14 mL/kg/min has been
recognized as one of the relative indications for transplantation, because
patients who achieve a measurement that is higher than 14 mL/kg/min have a 1-year
mortality rate similar to that of patients who undergo transplantation (i.e., >
90%). However, some debate exists regarding the optimal cutpoint that separates
survivors from nonsurvivors, and studies have not consistently defined the timing
of the test relative to optimization of medical therapy. It has also been debated
which hemodynamic variables, at rest or during exercise, should be used in
combination with peak VO2 to optimally stratify risk in these patients. This
article reviews the applications of cardiopulmonary exercise testing in prognosis
among patients with chronic heart failure.
PMID- 9649937
TI - Changing the remodeling process in heart failure: basic mechanisms and laboratory
results.
AB - Heart failure continues to be a major source of death and disability, and
concepts and understanding of the disorder continue to evolve. There is now
widespread recognition that myocardial remodeling is an important driving force
behind the progression of heart failure. Both scientists and clinicians strive to
understand the remodeling process better. Several animal models have been helpful
in this regard. Yet controversy and uncertainties persist regarding the
fundamental mechanisms of cardiac remodeling. To appreciate better the
contribution of diminished contractility to the syndrome of heart failure, a
number of laboratories have studied isolated cardiac myocyte function, both in
animal models and in humans with cardiomyopathy. Results have been mixed and
contradictory. A consistent theme found in many studies, however, is that the
cells assume a more elongated shape. There may or may not be concurrent
incremental changes in myocyte transverse diameter, depending on the model under
study. At least two groups have claimed that maximal contractile properties of
myocytes isolated from human failing hearts and from animals with experimental
heart failure are normal, but this may depend on where the cells are taken in
reference to acute myocardial injury. There are some important model-specific
considerations when interpreting the results of isolated myocyte studies.
Nevertheless, such experiments reinforce the concept that structural changes
during cardiac remodeling, including myocyte growth, deposition of collagen, cell
dropout, and perhaps myocyte slippage, all contribute to the architectural
changes in the geometry of the left ventricle. The quantitative contribution that
each structural change makes is not yet entirely clear. Studies in humans suggest
that myocyte elongation may be the dominant mechanism, but it cannot account for
the disproportionate increase in chamber size relative to myocyte length.
Therefore, myocyte slippage is likely making some contribution to cardiac
remodeling. Whether the remodeling process can be reversed is currently a topic
of great research interest. Preliminary data from studies of left ventricular
assist devices and beta-adrenergic blockers suggest that attenuation of
progression and perhaps even reversal of remodeling is possible.
PMID- 9649938
TI - Ventricular remodeling and its prevention in the treatment of heart failure.
AB - Ventricular remodeling refers to changes in left ventricular (LV) geometry, mass,
and volume in response to myocardial injury or alterations in load. The extent of
LV dilatation or remodeling after myocardial infarction (MI) or in patients with
heart failure is a strong predictor of both morbidity and mortality. Based on
these observations, it is clear that LV remodeling is a maladaptive process. Two
classes of drugs appear to inhibit LV remodeling. A large amount of data support
the use of angiotensin-converting enzyme (ACE) inhibitors to improve survival and
to prevent progressive remodeling. In addition, recent studies suggest that beta
adrenergic blockers have a beneficial effect on both survival and remodeling.
These data support a causative role of the renin-angiotensin system and perhaps
the sympathetic nervous system in this process. Thus, ACE inhibitors and possibly
beta-blockers should be part of the pharmacologic regimen for the treatment of
patients with LV dysfunction to prevent progressive LV remodeling.
PMID- 9649939
TI - Genetic risk factors for myocardial infarction.
AB - Myocardial infarction (MI) is a complex phenotype caused by interaction of a
number of genetic and environmental factors. A genetic susceptibility to MI was
observed in a familial aggregation and studies in twins. Advances in molecular
genetics have led to identification of a number of potential genetic risk factors
for MI, such as variants of genes involved in vascular homeostasis, thrombosis,
and lipid metabolism. Functional variants of angiotensin-1-converting enzyme
(ACE), beta-fibrinogen, plasminogen activator inhibitor-1,
methylenetetrahydrofolate reductase, glycoprotein Illa, and many apolipoprotein
genes are considered excellent candidate risk factors for MI. Interaction of the
susceptibility genes with modifier genes, environmental factors, and conventional
risk factors results in the final phenotype of MI. Understanding the complex
interaction between these factors is expected to provide significant insights
into the pathogenesis of MI and lead to development of genetic-based risk
stratification, prevention, and treatment.
PMID- 9649940
TI - Molecular aspects of myocarditis.
AB - The mechanisms of pathogenesis of myocarditis have remained elusive. Despite the
demonstration a decade ago that persistent viral infection of the myocardium
occurred in many patients, a clear description of the pathologic progression has
not been forthcoming. Over the past year, a number of studies have added to the
data defining the crucial roles of cytokine expression in the myocardium and the
aberrant induction of apoptosis. Further, a mouse model of myocarditis resulting
from the myocardial expression of tumor necrosis factor-alpha has been described.
In addition, the identification of the common coxsackievirus B and adenovirus
receptor has offered an explanation for the puzzling observation that these
highly distinct virus types both cause cardiac disease. Finally, the near
eradication of endocardial fibroelastosis associated with persistent mumps virus
infection by vaccination supports the notion that coxsackievirus B and adenovirus
vaccines may help reduce the incidence of myocarditis.
PMID- 9649941
TI - The genetics of midline and cardiac laterality defects.
AB - Left-right asymmetric looping of the cardiac tube during embryogenesis places the
segments of the cardiac tube that give rise to the left and right chambers into
their appropriate spatial orientation. Cardiac looping is required for subsequent
formation of septa, valves, and outflow tract. Defects in embryonic left-right
axis formation represent a significant portion of congenital heart malformations.
Recent discoveries make it apparent that the orientation of cardiac tube looping
is dependent on a cascade of genes in noncardiac embryonic cells, including
lateral cells and midline cells, before neural tube closure. These observations
suggest a linkage between complex cardiac defects and subtle midline defects in
early embryos.
PMID- 9649942
TI - Mitochondria and heart disease.
AB - Because the myocardium depends heavily on oxidative metabolism, it is not
surprising that genetic errors of mitochondrial function often result in
cardiomyopathies. The emphasis of this review is on disorders of the respiratory
chain, the only area of cell metabolism that is under dual genetic control: 1)
the mitochondrial genome (mtDNA) encodes 13 subunits of respiratory chain
complexes, and 2) the nuclear genome not only encodes all other respiratory chain
proteins, but also mitochondrial translocases, components of the mitochondrial
protein transport machinery, and factors that are essential for mtDNA
transcription, translation, and replication. Mitochondrial cardiomyopathies due
to mutations in the nuclear DNA are inherited as mendelian traits involving
structural or enzyme proteins of the respiratory chain, mitochondrial protein
importation, or the dialogue between the two genomes. Mitochondrial
cardiomyopathies due to mtDNA mutations can be sporadic or inherited as maternal
traits and follow the rules of "mitochondrial genetics," which are outlined
briefly. MtDNA mutations can cause isolated cardiomyopathies or, more often,
multisystem disorders of which cardiac involvement is a major component. We
review recent advances in this rapidly expanding field and briefly discuss
pathogenetic problems and the mitochondrial theory of presbycardia.
PMID- 9649943
TI - Molecular genetics of Marfan syndrome and Ehlers-Danlos type IV.
AB - Two inherited disorders of connective tissue have major cardiovascular
complications, Marfan syndrome and Ehlers-Danlos syndrome type IV. Major progress
has been made toward understanding both the genetic defect and the molecular
pathogenesis of these two disorders. Marfan syndrome results from mutations in
the FBN1 gene, which encodes fibrillin-1, an extracellular matrix component found
in structures called microfibrils. Histologic characterization of the effect of
FBN1 mutations on fibrillin-1 cellular processing and microfibril formation has
provided insights into fibrillin-1 function. Ehlers-Danlos syndrome type IV
results from mutations in the COL3A1 gene, which encodes the polypeptides in type
III collagen. Despite advances in the molecular genetics of these two disorders,
there is not a molecular diagnostic test for these syndromes based on the
identification of gene mutations. Marfan syndrome remains primarily a clinical
diagnosis. Biochemical analysis of the amount of type III collagen produced by
dermal fibroblasts has proven to be a powerful diagnostic test for Ehlers-Danlos
syndrome type IV.
PMID- 9649944
TI - Gene therapy and cardiovascular disease.
AB - This article provides the cardiologist with an overview of recent basic research
relevant to the application of somatic cell gene therapy against cardiovascular
disease. Somatic cell gene therapy simply refers to the use of genes as medicine,
but this is a potent form of medicine that will bring major advances to nearly
every form of medical practice. In the field of cardiology, research suggests
that gene therapy may find application against nearly every form of
cardiovascular disease. Although it is not possible to review every advance in
the field, this article does provide an overview of some of the gene therapy
approaches currently being pursued against atherosclerosis, thrombosis,
restenosis, myocardial infarction, hypertension, heart failure, and transplant
rejection.
PMID- 9649945
TI - Genetic aspects of supravalvular aortic stenosis.
AB - Supravalvular aortic stenosis (SVAS) occurs as an autosomal dominant trait or as
part of the phenotype of the usually sporadic condition Williams syndrome. SVAS
is the result of mutation or deletion of the elastin gene (ELN), located at
chromosome 7q11.23. Thus, SVAS may be more appropriately termed an elastin
arteriopathy. Studies have demonstrated various point mutations and intragenic
deletions of ELN resulting in nonsyndromic SVAS. Individuals with Williams
syndrome are hemizygous for the elastin gene, owing to a 1 to 2 megabase deletion
of a portion of the long arm of chromosome 7 that encompasses ELN. This
submicroscopic deletion is readily detected by fluorescent in-situ hybridization,
useful in the diagnosis of Williams syndrome. The severity of SVAS is quite
variable, both in series of Williams syndrome patients and within SVAS kindreds,
suggesting that other genetic factors are involved in expression of the
phenotype. Experiments with elastin knockout mice will likely yield clues
regarding the role of elastin in arterial morphogenesis and the pathogenesis of
obstructive vascular disease.
PMID- 9649947
TI - Molecular genetics.
PMID- 9649946
TI - Cardiac failure.
PMID- 9649948
TI - A simplified diagnostic test for ambulatory screening of peripheral diabetic
neuropathy.
AB - The reliability and reproducibility of Michigan Neuropathy Screening Instrument
(MNSI), a recently proposed simple test for ambulatory screening of peripheral
diabetic neuropathy (PDN), was evaluated on 80 diabetic patients. MNSI was
carried out by two diabetologists and repeated after a week. It consisted of the
sum of scores varying from 0 to 1 for each abnormality revealed in foot
appearance, achilles reflexes presence and vibratory threshold (VPT) by tuning
fork (maximum score = 8). Then patients had to go to neurologist for PDN
diagnosis by a quantitative neurological examination and electrophysiological
evaluation, the so named Michigan Diabetic Neuropathy Score (MDNS) and the
results compared with MNSI score according to one of the two observers. The inter
observer reproducibility of MNSI was 88.75% the within observer reproducibility
was 95 and 94%, respectively, for each observer with good correlation between the
two measurements (P < 0.001). The MNSI score of 2.5 as a cut-off appeared to be
reliable for ambulatory screening of suspected PDN (false positive and false
negative = 2.5%; specificity and sensitivity = 75% and 78.6%, respectively). In
conclusion MNSI by using 2.5 score as cut-off may be considered a rapid, simple,
reproducible and reliable test for rapid ambulatory screening of PDN from the
diabetologists.
PMID- 9649949
TI - Islet cell surface antibodies (ICSA) do bind to human pancreas: computerised,
quantitative determination of ICSA using both pre- and postembedding
immunocolloidal techniques.
AB - Islet cell surface antibodies (ICSA) have been demonstrated significantly more
often in serum of patients with IDDM and their relatives than in healthy
controls, but some investigators have been unable to show binding to human
islets. It has therefore been suggested that ICSA is an artefact. We have
localised and quantified ICSA binding to different specimens, including human
pancreas. ICSA-positive and ICSA-negative patients' serum, determined by a RIA
method, were incubated with ultrathin sections of rat insulinoma (RIN5AH) cells,
stained with Goat-anti-human IgG conjugated with 10 nm gold particles. Sections
were viewed in transmission electron microscopy (Mag. 30,000 x) and image
analyses was used to calculate immunolabelling. To test cell specificity we used
(RIN5AH-cells, rat tumour cells producing growth hormone (GH3), normal human
pancreas, human insulinoma, and mice liver). Sections showed good morphology.
ICSA-positive sera, with or without islet cell antibodies (ICA) gave always
higher immunocolloidal labelling then ICSA-negative sera on RIN5AH sections.
Thus, the colloidal gold technique could confirm the ICSA results determined with
RIA. Immunolabelling was pronounced on normal human pancreas and human insulinoma
cells, but none was found on GH3-cells or mice liver cells. ICSA is not an
artefact but do exist and bind to human islet cells and therefore maybe can be
used as a marker for IDDM immunity.
PMID- 9649950
TI - Changing prevalence of retinopathy in newly diagnosed non-insulin dependent
diabetes mellitus patients in Hong Kong.
AB - In this retrospective study, the prevalence of chronic microangiopathic
complications was determined in 474 Chinese patients with non-insulin dependent
diabetes mellitus (NIDDM) who presented within 1 year of diagnosis to the
diabetes clinic from January 1990 to December 1996. Mean age (+/- S.E.) was 53.6
(+/- 0.6) years. The overall prevalence of retinopathy was 21.9%. A significant
increase was observed from 1990 to 1994 (P < 0.005), with the prevalence being
14.8, 13.0, 24.5, 32.3 and 35.4%, respectively, in consecutive years. A
decreasing prevalence was seen from 1994 to 1996 (P < 0.001), being 8.2 and 7.4%
in 1995 and 1996, respectively. A total of 95% of patients had nonproliferative
retinopathy--proliferative retinopathy was found in 5% only. The overall
prevalence of clinical nephropathy (proteinuria > 0.5 g/day) was 3.7%. Clinical
neuropathy (increased vibration perception threshold) was found in 12.8% of
patients. Patients with retinopathy and neuropathy were older (P < 0.0001 and P <
0.005, respectively) than those without the complications and systolic
hypertension was more prevalent in patients with retinopathy (P < 0.05). In
conclusion, a high prevalence of diabetic microangiopathic complications,
especially of retinopathy, is present in newly diagnosed NIDDM patients in our
population. It remains to be determined whether the changing prevalence of
retinopathy at diagnosis bears any relationship to the increasing public
awareness of diabetes and its complications in Hong Kong in recent years.
Examination for chronic microangiopathic complications should be carried out in
all newly diagnosed NIDDM patients.
PMID- 9649951
TI - Combination insulin and sulfonylurea therapy in insulin-requiring type 2 diabetes
mellitus.
AB - PURPOSE: To determine the effect(s) on glucose control, insulin dose, and
circulating insulin levels of the addition of a sulfonylurea (glipizide) to the
treatment regimen of patients with insulin-requiring type 2 diabetes mellitus.
PATIENTS AND METHODS: Thirty seven patients with type 2 diabetes mellitus taking
insulin for at least 1 year prior to study and treated with > or = 40 U of
insulin per day were recruited for a randomized, double-blind, placebo
controlled, crossover trial. Patients were treated with 3 months of insulin +
placebo (I + P) and 3 months of insulin + glipizide (I + G), with an intermediate
1 month washout period using insulin therapy alone. Adjustments were made
initially to the maximum dose of glipizide (40 mg/day), followed by insulin dose
adjustments. Twenty-nine of the 37 patients demonstrated a significant C-peptide
response to Ensure and were selected for analysis. RESULTS: The fasting plasma
glucose in the I + G arm was 6.8 (121.8 mg/dl) vs. 8.7 mmol/L (156.0 mg/dl) in
the I + P arm, P < 0.001. Mean plasma glucose over 24 hours was 9.8 (176.9 mg/dl)
for I + G vs. 11.3 mmol/L (203.8 mg/dl) for I + P, P < 0.001. Glycated hemoglobin
was significantly different (9.8 I + G vs. 11.4% I + P, P < 0.008). The total
daily insulin dose required was significantly lower with I + G (69.1 vs. 87.3 U,
P < 0.0005). However, there were no significant differences in free insulin
levels. CONCLUSION: The addition of a sulfonylurea (glipizide) to insulin therapy
in patients with insulin-requiring type 2 diabetes mellitus taking large doses of
insulin results in a rapid and substantial improvement in glucose control despite
a significant reduction in insulin dose. Therefore, this form of combination
therapy should be considered for patients with the above characteristics whose
diet and exercise programs are correct but whose response to insulin therapy is
inadequate.
PMID- 9649952
TI - Quantification of apolipoprotein AI-containing lipoprotein particles in non
insulin-dependent diabetes mellitus.
AB - Quantification of LpAI (lipoprotein particles containing apolipoprotein AI not
associated with apolipoprotein AII) was performed through an electroimmunoassay
on serum from 49 non-insulin-dependent diabetic patients (mean age 60 +/- 9
years) and 53 age-matched control subjects of both sexes not affected by coronary
heart disease. Serum lipid and lipoprotein levels were not significantly
different between the two groups. Serum levels of LpAI determined for diabetic
patients did not differ from those of control subjects, while concentrations of
LpAI in men were significantly lower than in women, both among diabetics (P <
0.05) and controls (P < 0.005). Serum levels of apolipoprotein AI and high
density lipoprotein cholesterol were significantly correlated with those of LpAI
(P < 0.005, for both variables). On the contrary, levels of LpAI/AII (lipoprotein
particles containing both apolipoprotein AI and AII) were significantly increased
in diabetic patients (P < 0.005).
PMID- 9649953
TI - Onset age-dependent variations of three islet specific autoantibodies in Japanese
IDDM patients.
AB - The age related incidence rate of insulin-dependent diabetes mellitus shows a
bimodal distribution, not only in Caucasians but also in Japanese. To evaluate
the onset age-related autoimmune profile at presentation in insulin-dependent
diabetes mellitus (IDDM), glutamic acid decarboxylase (GAD) autoantibody, islet
cell antibody (ICA), and insulin autoantibody (IAA) were measured in 137 newly
diagnosed Japanese IDDM patients with onset ages between 0-29 years. The
prevalence of GAD autoantibody was significantly increased from the lowest (32%)
in the 0-5 years onset age group to 75% in the 13-19 years onset age group (P <
0.05), whereas the IAA prevalence significantly decreased from the peak (48%) in
the 6-12 years onset age group to 10% in the 20-29 years onset age group (P <
0.05). The ICA prevalence was increased from the lowest (32%) in the 0-5 years
onset age group to the highest (53%) in the 20-29 years onset age group similar
to that for the GAD autoantibody. Such results demonstrate that there was age
related autoimmune characteristics at presentation of IDDM in Japanese as well as
in Caucasians.
PMID- 9649954
TI - Clinical classification of diabetes in tropical west Africa.
AB - The objective of this work was to classify and describe the different types of
diabetic patients detected in West Africa. In four health centres (three in Ivory
Coast, one in Niger) 310 new cases were detected and followed up over 1 year.
Classification was based on age at diagnosis, BMI, ketonuria, basal and
stimulated C-peptide levels at inclusion, and response to antidiabetic therapy.
In this population, males were predominant (sex ratio = 2.40), and random blood
glucose levels very high at screening (mean +/- SE, 18.6 +/- 0.4 mmol/l). Only
one case of fibrocalculous pancreatic diabetes and one possible case of diabetes
mellitus related to malnutrition were detected. IDDM was diagnosed in 11.3% of
the patients, half of them above 35 years. Leanness was observed in 59% of the
patients with NIDDM. A dramatic decrease of fasting blood glucose was observed in
all groups after 2 months of treatment, especially in NIDDM. As IDDM and non
obese NIDDM presented great similarities before treatment, even for C-peptide
levels, a point score system is proposed to classify these two groups at
baseline. In conclusion, it is confirmed that the form of diabetes previously
defined as related to malnutrition is a very rare entity in black African
populations. In contrast, African diabetes is characterised by the high
proportion of NIDDM patients with low BMI, and reduced beta-cell function, rarely
associated to ketonuria. This form of diabetes seems to be adequately controlled
with oral hypoglycaemic drugs and/or diet in the year following diagnosis.
PMID- 9649955
TI - Hypertension and nephropathy in diabetes mellitus: what is inherited and what is
acquired?
AB - Prolonged duration of diabetes mellitus, poor long term glycemic control and
raised blood pressure have all been clearly related to the development of
diabetic nephropathy. Evidence exists to suggest that a subset of individuals
with diabetes have a genetic predisposition to diabetic nephropathy. Cases of
diabetic nephropathy cluster in families and a parental history of hypertension
is more common in patients with diabetic nephropathy. Current evidence suggests
an important role for hypertension in the genetic susceptibility to diabetic
nephropathy but the extent of this is unknown. While cellular and animal studies
have generated a plethora of data regarding mechanisms involved in the role of
hypertension and diabetic nephropathy, these are not helpful for drawing
conclusions in humans. In the following review, we examine the available
clinical, epidemiologic and family studies to assess the relationship between the
development of hypertension and diabetic nephropathy in IDDM and NIDDM. We will
demonstrate the differences in the epidemiology of hypertension in diabetes
depending on the type of diabetes and thus, move the emphasis of nephropathy
susceptibility away from hypertension per se. We hope to emphasize instead the
homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a
common genetic susceptibility exists for all types of diabetes and is conditional
on cumulative exposure to hyperglycemia. Regarding the interaction of
hypertension and nephropathy in diabetes mellitus, any conclusions at this time
about what is inherited and what is acquired must be regarded as speculative.
However we will discuss some potential mechanisms of hypertension in the
evolution of nephropathy and we will allude to the role for novel genetic studies
in the search for nephropathy susceptibility gene(s).
PMID- 9649956
TI - Salt sensitivity: concept and pathogenesis.
AB - Almost two decades ago, the existence of a subset of essential hypertensive
patients, who were sensitive (according to the increase in blood pressure levels)
to the intake of a diet with a high salt content, was described. These patients
are characterized by an increase in blood pressure and in body weight when
switched from a low to a high sodium intake. The increase in body weight is due
to the incapacity of the kidneys to excrete the whole intake of sodium until
renal perfusion pressure (mean blood pressure) attains a level that is able to
restore pressure-natriuresis relationship to values that enable the kidney to
excrete the salt ingested or administered intravenously. Salt sensitivity does
not seem to depend on the existence of an intrinsic renal defect to handle
sodium, but on the existence of subtle abnormalities in the regulation of the
sympathetic nervous system, the renin-angiotensin system or endothelial function.
It is also relevant that organ damage secondary to arterial hypertension, has
been shown in animal models and in hypertensive humans sensitive to a high salt
intake to be significantly higher when compared with that of salt-resistant
animals or humans. Interestingly, in humans, salt sensitivity has been shown to
correlate with microalbuminuria, an important predictor of cardiovascular
morbidity and mortality, which correlates with most of the cardiovascular risk
factors commonly associated with arterial hypertension. One of these factors is
insulin resistance, that usually accompanies high blood pressure in overweight
and obese hypertensives. Insulin resistance and hyperinsulinism are present in a
significant percentage of hypertensive patients developing cardiovascular
symptoms or death. For these reasons, therapy of arterial hypertension must be
directed, not only to facilitate the lowering of BP level, but also, to halt the
mechanisms underlying the increase in BP, when salt intake is increased.
Furthermore, therapy must preferably improve the diminished insulin sensitivity
present in salt-sensitive subjects that contribute independently to increased
cardiovascular risk.
PMID- 9649957
TI - Hypertension and macrovascular disease--the killing fields of NIDDM.
AB - Diabetes mellitus and particularly non-insulin-dependent diabetes mellitus
(NIDDM) increases the risk for all manifestations of: (a) atherosclerotic
vascular disease; (b) coronary heart disease (CHD); (c) cerebrovascular disease;
and (d) peripheral vascular disease. NIDDM is known to be associated with several
adverse cardiovascular risk factors, including: (i) hypertension; (ii) obesity;
(iii) central obesity; (iv) hyperinsulinemia; and (v) serum lipid and lipoprotein
abnormalities, characterized mainly by elevated serum total triglycerides and low
high-density lipoprotein cholesterol. This review will discuss the prevalence of
hypertension in NIDDM, the role of hypertension to increase the risk for
macrovascular complications in NIDDM and finally trial evidence for the
beneficial effect of blood pressure lowering in patients with NIDDM.
PMID- 9649958
TI - Progression of diabetic nephropathy. A focus on arterial pressure level and
methods of reduction.
AB - It is well accepted that a reduction of arterial pressure to levels of less than
140/90 mmHg will slow the decline in renal function among patients with diabetic
nephropathy. More recently it is appreciated that the reduction of arterial
pressure to levels much below 130/85 mmHg provides even greater levels of
protection against the progression of renal disease. Given that the achievement
of blood pressure reduction to such a level requires more than one medication and
that the patient's compliance is best with a once-daily medication, it makes
sense to combine antihypertensive medications so as to maximize the benefit. In
this way, fixed dose combination medications yield synergistic effects on blood
pressure reduction while providing, in some cases, maximal benefit to
preservation of renal function. Such a combination is the verapamil/trandolapril
combination. This paper discusses in great detail the advantages of blood
pressure reduction and the types of medications that may achieve both protection
against diabetic nephropathy progression as well as blood pressure reduction.
PMID- 9649959
TI - Is antihypertensive treatment the same for NIDDM and IDDM patients?
AB - The prevalence of abnormally elevated albumin excretion rate (> 30 mg/24 h) is
approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM)
diabetic patients. Diabetes has become the leading cause of end-stage renal
failure in the US, Japan and Europe. Approximately 90% of the direct and indirect
cost of caring for diabetic patients are spent on the complications of diabetes.
Identification of patients at high risk of developing diabetic nephropathy is
possible by screening for microalbuminuria (30-300 mg/24 h). Elevated urinary
albumin excretion rate indicates a substantially increased mortality risk in
diabetic patients. Randomised controlled trials in normotensive IDDM and NIDDM
patients with persistent microalbuminuria indicate that ACE inhibitors diminish
urinary albumin excretion rate, postpone it and may even prevent progression to
clinical overt nephropathy. These findings indicate that screening and
intervention programs are likely to have life saving effects and lead to
considerable economic savings. Systemic blood pressure elevation to a
hypertensive level is an early and frequent phenomenon in diabetic nephropathy.
Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more
frequently in patients with nephropathy. Systemic blood pressure elevation and to
a lesser degree albuminuria accelerate the progression of diabetic nephropathy.
Effective blood pressure reduction with non-ACE-inhibitors and/or ACE-inhibitors
frequently in combination with diuretics: (a) reduces albuminuria; (b) delays the
progression of nephropathy; (c) postpones renal insufficiency; and (d) improves
survival in IDDM and NIDDM patients with diabetic nephropathy. A specific renal
protective effect of ACE-inhibitors in diabetic nephropathy has been demonstrated
in IDDM patients with moderately reduced kidney function (s-creatinine > 133
mumol/l) while the data conflict with NIDDM patients. Antihypertensive treatment
for diabetic nephropathy simultaneously extends life and saves money. Finally,
reduced risk of fatal and non-fatal cardiovascular events have been demonstrated
when diabetic patients with isolated systolic hypertension are treated with blood
pressure lowering agents. Absolute risk reduction with active treatment compared
to placebo was twice as great for the diabetic versus non-diabetic patients
(101/1000 versus 51/1000 randomised participants at the 5-year follow-up),
reflecting the higher risk of diabetic patients. In conclusion, early detection
and aggressive treatment of arterial hypertension with ACE-inhibitors, long
acting calcium antagonist and low dose diuretics as first line drugs are highly
warranted in diabetic patients with or without diabetic renal disease.
PMID- 9649960
TI - Prognosis of diabetic nephropathy: how to improve the outcome.
AB - Chronic renal diseases, including diabetic nephropathy, evolve to terminal renal
failure by a process leading to progressive parenchimal damage which appears
relatively independent of the initial insult. When glomerular permselectivity is
lost, proteins filtered through the glomerular capillary, through proximal
tubular cell activation and up-regulation of genes of inflammatory and vasoactive
mediators, may give rise to an inflammatory reaction that in the long-term can
contribute to renal scarring. If this interpretation is correct, the best
approach to try to retard the progression of several renal diseases would be to
limit the excessive traffic of macromolecules throughout the glomerular capillary
by molecules, as the angiotensin-converting-enzyme (ACE) inhibitors, that may
help restore perm-selective properties to normal. Thus, the present review
addresses the mechanism(s) of the renal protective effect of ACE inhibitors and
analyzes the evidence so far available of their salutary effect in human
nephropathies, with particular focus on diabetic nephropathy. The issue of
whether ACE inhibitors alone or in combination with other antihypertensives
(namely non-dihydropyridinic calcium channel blockers) may even prevent the onset
of nephropathy at the stage of normoalbuminuria is discussed.
PMID- 9649961
TI - Investigation of hallucinogenic and related beta-carbolines.
AB - Certain beta-carbolines are known to be hallucinogenic in humans, and several
produce stimulus effects in animals similar to those of the classical
hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Classical
hallucinogens bind at 5-HT2 serotonin receptors and these receptors are thought
to play a role in their mechanism of action. In the present study, we examined
the binding of 15 beta-carbolines at rat 5-HT2A and 5-HT2C receptors. Affinities
(Ki values) of the beta-carbolines ranged from about 100 nM to greater than
10,000 nM depending upon the degree of saturation of the pyridyl ring, and upon
the presence and location of methoxy substituents in the benzenoid ring. In a
further study, six rats were trained to discriminate the hallucinogenic beta
carboline harmaline (3.0 mg/kg, i.p.) from vehicle using a VI-15s schedule of
reinforcement. This represents the first time a hallucinogenic beta-carboline has
been used as a training drug in a drug discrimination study. Administration of
DOM to the harmaline-trained animals resulted in 76% harmaline-appropriate
responding at 1.25 mg/kg DOM and disruption of behavior at a higher dose. Taken
together, the results of the present investigation demonstrate that: (a) certain
beta-carbolines bind at 5-HT2 receptors; (b) that harmaline serves as a training
drug at 3.0 mg/kg in drug discrimination studies with rats as subjects; and that
(c) there is some similarity between the stimulus effects produced by harmaline
and DOM.
PMID- 9649962
TI - Predictors of cessation of marijuana use: an event history analysis.
AB - Event history analysis was applied to monthly life and drug histories of a
representative community sample of 706 marijuana users, followed from ages 15-16
to 34-35, to investigate factors associated with cessation of marijuana use from
adolescence to adulthood. In addition to age and gender, the most important
determinants of cessation are the phenomenology of marijuana use, social role
participation, depressive symptoms and deviance. Frequent users, those who
started using early and those who use illicit drugs other than marijuana are more
likely to continue their marijuana use. Using marijuana for social reasons
accelerates cessation, using to change one's mood reduces cessation. Becoming
pregnant and a parent is the most important social role leading to marijuana
cessation for women. There is also a very important experimental effect of the
interview itself on the reported timing of a cessation. The effect of a social
context favorable to marijuana use appears to reflect selection rather than
social influence.
PMID- 9649963
TI - Separation of the locomotor stimulant and discriminative stimulus effects of
cocaine by its C-2 phenyl ester analog, RTI-15.
AB - During a routine evaluation of several analogs of cocaine, we observed that the C
2 phenyl ester, RTI-15, appeared to suppress motor activity in rats. We
subsequently examined RTI-15 for its cocaine-like stimulus effects as well as for
its locomotor activity effects. RTI-15 dose-dependently generalized from the
cocaine stimulus in rats trained to discriminate 10 mg/kg cocaine from saline
with complete substitution (> or = 80% cocaine-lever responding) occurring at 24
mg/kg. During automated locomotor activity tests in mice, cocaine (3-60 mg/kg)
dose-dependently increased activity counts and movement time across the entire 1
h test session. RTI-15, however, had little affect on activity counts and
movement time from 10-30 mg/kg, and decreased these measures at 60 mg/kg, the
highest dose tested. These results indicate that while changing the C-2 methyl
ester of cocaine to a C-2 phenyl ester increases dopamine-transporter
selectivity, it dissociates its locomotor activity effects from its
discriminative stimulus effects suggesting that the underlying mechanisms
mediating these effects are not identical.
PMID- 9649964
TI - A comparison of subjective, psychomotor and physiological effects of a novel
muscarinic analgesic, LY297802 tartrate, and oral morphine in occasional drug
users.
AB - This study compared the subjective, physiological and psychomotor effects of a
novel muscarinic analgesic (LY297802) and oral morphine in healthy volunteers.
Nine, non-dependent, occasional drug users participated in nine experimental
sessions in which they received the following conditions: placebo, 0.1, 0.3, 0.56
and 1 mg of oral LY297802 and 10, 30, 56 and 100 mg of oral morphine. Subjective
drug effects were assessed using the Visual Analog Scale (VAS), the Addiction
Research Center Inventory (ARCI) and subjective and objective agonist and
antagonist scales of the Adjective Rating Scale (ARS). These measures were
collected 30 min before and every 30 min post drug administration for a 4-h
period. Psychomotor performance was evaluated using the Digit Symbol Substitution
Test (DSST) at these same time intervals. Physiological measures were collected
continuously throughout the sessions. Oral morphine produced significant
increases in some subjective effects scales, including elevations on the VAS,
ARCI and ARS. In contrast, LY297802 did not engender changes different from
placebo on any of these indices. Morphine produced significant dose-dependent
effects in DSST performance, heart rate, blood oxygen saturation and pupil
diameter. LY297802 significantly and dose dependently increased heart rate, mean
arterial pressure and diastolic blood pressure. These results suggest that
LY297802 does not induce subjective effects similar to morphine, but that it has
some significant physiological effects.
PMID- 9649965
TI - Impulsivity and history of drug dependence.
AB - Impulsivity was contrasted between 32 subjects with a history of drug-dependence
(DRUG+) and 26 subjects with no drug use history (DRUG-) using both behavioral
and self-report measures. The hypothesis was that the DRUG+ group would be more
impulsive than the DRUG- group. Subjects in the DRUG+ group self-reported more of
a tendency toward impulsivity than the DRUG- group in the situations posed in
questionnaires. In the behavioural paradigm involving a choice between a smaller
intermediate reward and a larger but delayed reward, DRUG+ subjects selected the
impulsive option more often, but these differences were not significant. The
DRUG+ and DRUG- groups did differ on the mean delay interval for the larger
reward, indicating less ability to tolerate longer delays for the larger reward.
A frequency distribution of delay intervals for the larger reward indicated that
DRUG+ subjects were more likely to maintain very short intervals and less likely
to maintain longer intervals.
PMID- 9649966
TI - Effects of chronic opioid dependence and HIV-1 infection on pattern shift visual
evoked potentials.
AB - The goal of the present study was to examine the effects of opioid dependence,
alone and in combination with asymptomatic HIV-1 infection, on the pattern shift
visual evoked potential (PSVEP). For this purpose, three groups of patients were
evaluated, including patients characterized by: (1) a past history (2-4 months
abstinent) of DSM-IIIR opioid dependence (i.e. in partial remission); (2) a
recent history (7 days abstinent) of opioid dependence with ongoing methadone
maintenance; and (3) a recent history of opioid dependence, ongoing methadone
maintenance, and asymptomatic HIV-1 infection. A group of healthy, non-drug
dependent volunteers was also evaluated. Analyses revealed no PSVEP differences
between patients with a past history of opioid dependence and healthy volunteers.
There were also no PSVEP differences between methadone-maintained patients with
or without HIV-1 infection. Collectively, however, the two methadone maintenance
groups exhibited significant delays in the N75 and P100 components of the PSVEP
relative to the other two groups. The delay in N75 latency was strongly
correlated with self-reported years of heroin abuse, but not with years of
cocaine, alcohol, or other drug abuse. These results are interpreted as
reflecting an adverse effect of chronic opioid dependence on neural transmission
within primary visual areas of the brain.
PMID- 9649967
TI - Effects of nicotine on methadone self-administration in humans.
AB - The effects of nicotine abstinence, ad libitum smoking, and 0, 2, and 4 mg
nicotine gum on methadone self-administration were investigated. Five methadone
maintained patients with a history of smoking (18-30 cigarettes/day) were
recruited as subjects. Upon arrival expired carbon monoxide levels were measured
to confirm self-reported abstinence of 10-12 h. At 30 min prior to the methadone
self-administration session, two response options were concurrently available.
When a 64-button press requirement (FR64) was completed, 10 ml of 0.054 mg/ml
methadone solution, or vehicle, was delivered. Immediately following, and 30, 60,
90, and 120 min after the self-administration session, expired carbon monoxide
levels and typical symptoms of nicotine withdrawal were assessed. Relative to
abstinence, subjects consumed more methadone following the 4-mg nicotine gum and
ad libitum smoking conditions. Ratings of cigarette craving were significantly
less following ad libitum smoking or administration of 4-mg nicotine gum, than
following abstinence. Implications for understanding opioid and nicotine
interactions are discussed.
PMID- 9649968
TI - Using geographic information systems to assess spatial patterns of drug use,
selection bias and attrition among a sample of injection drug users.
AB - This study sought to assess whether frequency and type of drug use are
geographically located within the city of Baltimore independent of neighborhood
characteristics. The second goal was to assess geographic factors associated with
sample selection and attrition. The sample consisted of 597 inner-city injection
drug users who were enrolled in a HIV prevention study. The residential locations
were plotted using Geographic Information Systems (GIS) software. Three patterns
of drug use in the prior 6 months were examined: daily use of injection heroin,
daily use of injection cocaine and any use of crack cocaine. Daily use of cocaine
and any use of crack were found to be statistically associated with residing in
the western portion of the city and distance from the western district sexually
transmitted disease clinic. After adjusting for individual level characteristics
and neighborhood level variables, as measured by 1990 census tract data, daily
use of cocaine was found to be associated with residing in a more southern area
of the city and distance from the western district sexually transmitted disease
clinic, and any crack use was found to be associated with residing in a more
western area of the city and distance from the western district sexually
transmitted disease clinic. Men and younger participants were more likely to
reside further away from the study clinic as were individuals who dropped out of
the intervention condition. The results of this study suggest that type and
frequency of drug use is associated with specific geographic areas, independent
of neighborhood characteristics. These results have implications for the location
of drug prevention, needle exchange and other HIV prevention activities.
PMID- 9649969
TI - Computers in community-based drug and alcohol clinical settings: are they
acceptable to respondents?
AB - The use of computer technology is not new in the delivery of health services.
Previous studies have assessed the reliability and validity of computerised
surveys, relative to pen and paper versions or interviews or the acceptability of
computers in a range of treatment settings. Generally, these studies have
reported that the reliability, validity and acceptability of computer surveys is
at least comparable to more traditional survey methods. This study provides
evidence for the appropriateness of using computers in community-based drug and
alcohol clinical settings, reporting a high level of computer acceptability among
clients. The advantages of utilising computers in clinical settings, for
researchers and clinicians, are discussed.
PMID- 9649970
TI - Attention and memory in illicit amphetamine users: comparison with non-drug-using
controls.
AB - The purpose of this study was to clarify the extent of neuropsychological
impairment previously found among amphetamine users (McKetin and Mattick, 1997)
by comparing them with a non-drug-using control group. Amphetamine users who were
classified as low dependence (n = 15) or high dependence (n = 11) according to
the severity of dependence scale (SDS) were compared to non-drug-using control
subjects (n = 9) on indices of the Wechsler Memory Scale-Revised (WMS-R).
Dependent amphetamine users (high dependence group) performed approximately one
half of a standard deviation worse than controls on the verbal memory,
attention/concentration and delayed recall indices of the WMS-R but amphetamine
users who were less dependent (low dependence group) showed no impairment.
PMID- 9649971
TI - Regional cerebral blood flow during acute and chronic abstinence from combined
cocaine-alcohol abuse.
AB - Regional cerebral blood flow (rCBF) was assessed using SPECT and HMPAO in ten
cocaine abusers within 72 h of last cocaine use and then after 21 days of
abstinence. In comparison to normals the cocaine abusers had significantly
reduced rCBF in 11 of 14 brain regions with the largest reductions in the frontal
and parietal cortex and greater rCBF in the brain stem. These perfusion defects
appeared to be primarily due to combined alcohol and cocaine abuse and frontal
but not parietal defects appeared to resolve partially during 21 days of
abstinence.
PMID- 9649972
TI - A mathematical model of HIV transmission in NSW prisons.
AB - A mathematical model was developed to estimate HIV incidence in NSW prisons. Data
included: duration of imprisonment; number of inmates using each needle; lower
and higher number of shared injections per IDU per week; proportion of IDUs using
bleach; efficacy of bleach; HIV prevalence and probability of infection. HIV
prevalence in IDUs in prison was estimated to have risen from 0.8 to 6.7% (12.2%)
over 180 weeks when using lower (and higher) values for frequency of shared
injections. The estimated minimum (and maximum) number of IDU inmates, infected
with HIV in NSW prisons was 38 (and 152) in 1993 according to the model. These
figures require confirmation by seroincidence studies.
PMID- 9649973
TI - Prenatal cocaine exposure and school-age intelligence.
AB - Assessments of the possible consequences of prenatal exposure to cocaine have
been limited by lack of control for socio-demographic confounders and lack of
follow-up into the school years. We evaluated intelligence at ages 6-9 years in
88 children from a cohort of 280 born between September 1, 1985 and August 31,
1986 and identified at birth as cocaine-exposed, and in a group of unexposed (n =
96) births of comparable gender and birthweight. IQ scores did not differ between
children with and without prenatal exposure to cocaine (mean 82.9 vs. 82.4,
difference = 0.5 points, 95% CI-3.1, 4.1); results were unchanged with adjustment
for child height, head circumference and prior residence in a shelter or on the
street, and for caregiver IQ and home environment (mean difference = 2.2 points,
95% CI-1.5, 5.8).
PMID- 9649974
TI - The differential effects of alcohol consumption and dependence on adverse alcohol
related consequences: implications for the workforce.
AB - Previous literature has supported the hypothesis that high rates of alcohol
consumption are associated with adverse social consequences and that dependence
on alcohol has an effect on that relationship. The purpose of this paper is to
further specify the alcohol consumption-adverse consequences linkage by
developing and estimating a latent variable model that incorporates the mediating
effects of loss of control over alcohol consumption. This model is applied to
measures for three alcohol-related constructs--consumption, loss of control and
adverse consequences--incorporated in the 1991 National Household Survey on Drug
Abuse, for members of the primary workforce in the US. The research suggests that
workplace decision makers attempting to minimize the adverse workplace
consequences of alcohol abuse should implement procedures that assess and respond
to alcohol dependency rather than relying exclusively on detection of and
intervention with alcohol consumption per se.
PMID- 9649975
TI - Fluoxetine treatment of depressive disorders in methadone-maintained opioid
addicts.
AB - This study tested the effectiveness of fluoxetine as a treatment for depression
in a population of methadone-maintained opioid addicts. Methadone-maintained
opioid addicts (44) with depression received fluoxetine or placebo in addition to
their methadone, in a double-blind randomized trial, for 12 weeks. Depressive
symptoms decreased significantly overall with no significant differences between
the groups treated with fluoxetine versus placebo. In addition, drug use
outcomes, including cocaine and heroin self-reported use and urine toxicology
were measured. There was a significant decrease in heroin use in treatment, but
no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint.
In separately analyzing data for the subsample of subjects with the most severe
depression, there was a significant decrease in depression during treatment and a
significant decrease in self-reported cocaine use, but no medication effect on
either depressive symptoms or on cocaine use. This study suggests that fluoxetine
is not an effective agent in treating depression or cocaine use in this
population.
PMID- 9649976
TI - Accelerated lofexidine treatment regimen compared with conventional lofexidine
and methadone treatment for in-patient opiate detoxification.
AB - This open study compares an accelerated 5-day lofexidine regimen with orthodox 10
day lofexidine and methadone regimens in the treatment of opiate withdrawal in 61
polysubstance abusing opiate addicts. Significant differences in levels of
withdrawal symptoms were found on days 11, 13-15 and 17-20, symptoms resolving
most rapidly in the 5-day lofexidine treatment group, whilst withdrawal responses
in the 10-day lofexidine treatment group were intermediate between the 5-day
lofexidine and standard methadone treatment conditions. When the two lofexidine
regimens were separately compared with methadone the 5-day lofexidine treatment
was significantly more effective on day 10, 11 and 13-20, whilst the 10-day
lofexidine treatment was not significantly different from methadone. There were
no significant differences in rates of completion of detoxification between the
three treatments. Both the lofexidine treatment regimens had a similar effect on
blood pressure. Five patients experienced side effects which resolved with dose
reduction, all remaining in the study. An accelerated 5-day lofexidine regimen
may attenuate opiate withdrawal symptoms more rapidly than conventional 10-day
lofexidine or methadone treatment schedules without exacerbating hypotensive side
effects.
PMID- 9649977
TI - Treatment failure and methadone dose in a public methadone maintenance treatment
programme in Geneva.
AB - The aim of this study was to identify predictors of treatment failure in a
methadone maintenance treatment programme in Geneva. All patients (n = 149)
starting treatment between May 1993 and May 1995 were followed until end of
treatment or 31st July 1996. The proportion of depressed patients decreased
significantly over time, as did the proportion of those injecting illegal drugs.
The overall treatment failure was 21%. The probability of treatment failure was
higher for women than for men (RR 2.2, P = 0.03) and decreased in successive
cohorts. There was no correlation between the methadone dose at 2 months and
treatment outcome, probably because doses were individualised and the associated
level of psycho-social services high.
PMID- 9649978
TI - Autoradiographic analysis of cannabinoid receptor binding and cannabinoid agonist
stimulated [35S]GTP gamma S binding in morphine-dependent mice.
AB - The present study was designed to test the possible existence of changes in brain
cannabinoid receptors in morphine-dependent mice. To this end, we compared
cannabinoid receptor binding and WIN 55,212-2-stimulated [35S]guanylyl-5'-O
(gamma-thio)-triphosphate ([35S]GTP gamma S) binding in several brain regions of
mice chronically exposed to morphine or saline. The existence of opiate
dependence in morphine-injected mice was assessed by analyzing the well-known
jumping behavior induced by the blockade of opioid receptors with naloxone,
whereas these animals were unresponsive to the blockade of cannabinoid receptors
with SR141716. The different structures analyzed exhibited similar cannabinoid
receptor binding levels in morphine-dependent and control mice, with the only
exception of the globus pallidus, which exhibited a very small, but statistically
significant, increase. In addition, the activation of cannabinoid receptors with
WIN 55,212-2 increased [35S]GTP gamma S binding in most of the structures
examined. The increase was of similar magnitude in morphine-dependent and control
mice, except in the substantia nigra, where morphine-dependent mice exhibited
lesser [35S]GTP gamma S binding levels in basal conditions, although a
significantly higher WIN 55,212-2-stimulated binding. Other structures, such as
the central gray substance, where there was a poor agonist-induced stimulation in
control mice, exhibited, however, higher levels of WIN 55,212-2-stimulated
[35S]GTP gamma S binding in morphine-dependent mice, whereas these animals tended
to exhibit a higher [35S]GTP gamma S binding levels in basal conditions, although
a lesser and not statistically significant WIN 55,22-2-stimulated binding, in the
deep layers of the cerebral cortex. Thus, the data support the potential
existence of a specific effect of morphine in the coupling of cannabinoid
receptors to GTP-binding proteins, rather than on receptor binding, although this
was observed only in the substantia nigra and central gray substance.
PMID- 9649979
TI - Randomised double-blind comparison of lofexidine and clonidine in the out-patient
treatment of opiate withdrawal.
AB - This study compares the clinical response to lofexidine and clonidine in the out
patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised
double-blind study design. Patients were taking 40 mg or less methadone daily, or
equivalent amounts of other opiates. Fifty-eight percent of those starting
treatment completed detoxification, and were opiate free at 4 weeks: more
patients completed withdrawal in the lofexidine group, but the difference was not
significant. Clonidine produced more hypotensive effects: more home visits were
also required by medical staff. There was no other significant difference in side
effects. Both drugs can be used successfully in out-patient detoxification, but
lofexidine is more economical in regard to staff time.
PMID- 9649980
TI - Acute pain services: transition from the Middle Ages to the 21st century.
PMID- 9649981
TI - Who was the first to monitor blood pressure during anaesthesia?
PMID- 9649982
TI - Local vs. systemic immune and haemostatic response to hip arthroplasty.
AB - Local and systemic immune and haemostatic responses were studied in 10 patients,
aged 57-78 years, undergoing elective hip arthroplasty. Cytokines, soluble
cytokine receptors, interleukin-1 receptor antagonist, soluble adhesion
molecules, antithrombin, fibrin, soluble and fibrin D-dimer were analysed in
wound drainage blood and in blood taken from the systemic circulation for up to
24 h post-operatively. Wound drainage blood concentrations of cytokines,
interleukin-1 receptor antagonist and soluble cytokine receptors were increased
compared with those in the systemic circulation except for the soluble
interleukin-6 receptor. In wound drainage blood, soluble tumour necrosis factor
receptors (P < 0.05), interleukin-1 receptor antagonist (P < 0.05) and
interleukin-6 (P < 0.05-< 0.01) increased during the study period. In blood from
the systemic circulation interleukin-6 increased (P < 0.05) while the soluble
interleukin-6 receptor decreased (P < 0.05) compared with pre-operative values.
Concentrations of soluble adhesion molecules did not change. Wound drainage blood
showed marked hypercoagulation. After hip arthroplasty pro-inflammatory cytokines
and their inhibitors were mainly confined to the local trauma site. A
predominance for inhibitors was noted.
PMID- 9649983
TI - An audit of post-operative pain and nausea in day case surgery.
AB - A telephone audit was carried out on patients 24 hours after day case surgery. An
initial audit shortly after the day case opened indicated pain scores and nausea
that were considered unacceptable. Some 8.6% of patients called their family
doctor (GP) to visit their home in the post-operative period. Pre-operative
Piroxicam 20 mg was then initiated (in most patients) to reduce the pain scores,
which it did. Only one patient in 111 (0.9%) called their GP out, but nausea
scores remained unchanged. Methods to reduce this index are suggested.
PMID- 9649984
TI - Effect of diluent volume on post-operative analgesia and sedation produced by
epidurally administered midazolam.
AB - We have studied the optimal diluent volume for post-operative analgesia and
sedation produced by epidurally administered midazolam after upper abdominal
surgery. Sixty patients were randomly allocated to four groups of 15 patients.
When patients complained of pain after surgery, epidural midazolam 0.05 mg kg-1
in 3 mL saline (Group A), in 5 mL saline (Group B), in 10 mL saline (Group C) or
in 15 mL saline (Group D) were injected as a bolus. The sedation was better and
lasted longer in groups B and C than in the other two groups. Groups B and C also
had significantly more extensive areas of analgesia than groups A and D from 30
min after the administration of midazolam. The interval to the second request for
an analgesic was significantly shorter in Group D than in the other three groups.
Memory retention of the pin-prick examination was reported by four patients in
Group A. The present results indicate that 5-10 mL saline is the optimal volume
for epidural injection when using midazolam 0.05 mg kg-1 for post-operative
analgesia following upper abdominal surgery.
PMID- 9649985
TI - Sevoflurane anaesthesia in paediatric patients: better than halothane?
AB - Forty-two children (aged 2-16 years) were randomly assigned to receive either
sevoflurane (n = 21) or halothane (n = 21) in nitrous oxide/oxygen. After pre
medication with midazolam, anaesthesia was induced by facemask and the
anaesthetic concentration was increased until loss of eyelash reflex
(sevoflurane, 6%; halothane, 2.5%). Thereafter, 1-1.5 MAC of the inhalational
agents were maintained until skin closure. Intra-operative analgesia was provided
either by intermittent intravenous (i.v.) bolus doses of fentanyl (2-3 micrograms
kg-1) or by a regional blockade. Induction was smooth and the time to loss of
eyelash reflex was slightly shorter with sevoflurane than with halothane, the
difference not quite reaching statistical significance (P = 0.06). In both
groups, heart rate remained stable and blood pressure decreased significantly
during induction. Haemodynamic parameters remained stable during anaesthetic
maintenance; no cardiac dysrhythmias were observed. Emergence time with
sevoflurane was 12.9 min vs. 16.3 min with halothane, but this difference was not
statistically significant. It is concluded that sevoflurane is as suitable for
paediatric patients as halothane. The slightly faster emergence time offered by
sevoflurane over halothane was of no clinical significance in the present study.
PMID- 9649987
TI - Clonidine prolongs fentanyl-induced ventilatory depression.
AB - The aim of the present study was to investigate the effect of intravenously
(i.v.) administered fentanyl and clonidine on ventilation in 12 healthy male
volunteers (age 30.8 +/- 4.9 years) who either received fentanyl alone (1.5 > or
= micrograms kg-1) or fentanyl (1.5 > or = micrograms kg-1) in combination with
clonidine (3 > or = micrograms kg-1). The effect on ventilation was measured with
a CO2 rebreathing system. The respiratory depression caused by fentanyl
disappeared 120 min after injection. The corresponding slopes were 7430 +/- 2075
mL kPa-1 prior to (t0) and 6263 +/- 1864 mL kPa-1 120 min post-application (base
line vs. t120; P = 0.106). An impaired ventilatory response was observed during
CO2 rebreathing at t120 after the injection of fentanyl and clonidine. Before
drug administration, the slope of the response curves was 7700 +/- 2800 mL kPa-1,
which was reduced to 5480 +/- 2135 mL kPa-1 (P < 0.035) at t120. These data
suggest a prolongation of a fentanyl-induced ventilatory depression when used in
combination with clonidine.
PMID- 9649986
TI - Effective dose of granisetron for the prevention of post-operative nausea and
vomiting in patients undergoing laparoscopic cholecystectomy.
AB - This study was undertaken to determine the minimum effective dose of granisetron,
a selective 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of
post-operative nausea and vomiting (PONV) in female patients undergoing elective
laparoscopic cholecystectomy. In randomized, placebo-controlled, double-blind
study, 120 women were assigned to receive either placebo (saline) or granisetron
at three different doses (20 micrograms kg-1, 40 micrograms kg-1 or 80 micrograms
kg-1) intravenously immediately before the induction of anaesthesia. All patients
received standardized anaesthesia consisting of isoflurane and nitrous oxide in
oxygen. The incidence of PONV during the first 24 hours after anaesthesia was 43,
40, 13 and 13% after administration of placebo and granisetron 20 micrograms kg
1, 40 micrograms kg-1 and 80 micrograms kg-1, respectively (P < 0.05, overall
Fisher's exact probability test). Adverse effects post-operatively were not
different among the groups. In conclusion, granisetron 40 micrograms kg-1 is the
minimum effective dose in the prevention of PONV after laparoscopic
cholecystectomy.
PMID- 9649988
TI - Pharmaco-economic evaluation of a disposable patient-controlled analgesia device
and intramuscular analgesia in surgical patients.
AB - The present study contrasted the pharmaco-economics and analgesic efficacy of
intramuscular (i.m.) opioid treatment with a parenteral disposable patient
controlled analgesia (PCA) system in two groups of 20 female patients (ASA I-II,
aged 35-69 years) scheduled for abdominal hysterectomy. The PCA group received a
continuous infusion of 1.5 mg h-1 piritramide, a mu-opioid receptor agonist, with
incremental doses of 1.5 mg (lock-out interval = 15 min). The i.m. group received
0.3 mg kg-1 piritramide i.m. when requested by the patient with a minimum
interval of 5 h. Pain intensity, sedation and the functional recovery of the
patients were followed for 72 h post-operatively. The sum of pain intensity
differences (SPID) was used as a measure of analgesic efficiency. Equipment and
drug costs, and the demand on nursing time were recorded over 3 days post
operatively. The costs of PCA and i.m. therapies per patient were used to
calculate the cost-benefit (cost of treatment vs. nursing time) and cost
effectiveness (cost of treatment vs. SPID) analyses. Both treatments initially
provided comparable analgesia, but PCA was more efficient after 16 h and
significantly reduced nursing time for pain treatment (PCA = 61 +/- 4 min, i.m. =
88 +/- 5 min; P < 0.001). Functional recovery was not different for either
treatment. Cost analysis indicated a better cost-benefit ratio for the i.m.
treatment (0.35 vs. 1.1 for PCA treatment), but a similar cost-effectiveness for
both treatments (PCA = 1.9 Belgian Francs (BEF) unit-1 SPID; i.m. = 1.7 BEF unit
1 SPID).
PMID- 9649989
TI - Addition of droperidol to morphine administered by the patient-controlled
analgesia method: what is the optimal dose?
AB - Eighty patients were recruited into a double-blind, randomized trial to find the
optimal dose of droperidol for addition to the patient-controlled analgesia (PCA)
morphine infusate for female patients undergoing gynaecological surgery. A
standardized anaesthetic technique was employed. Post-operative analgesia was
provided by PCA morphine. Patients were allocated at random into one of four
treatment groups receiving with each PCA morphine bolus: (1) droperidol 0.05 mg;
(2) droperidol 0.10 mg; (3) droperidol 0.15 mg; and (4) droperidol 0.20 mg,
respectively. The incidence of post-operative nausea and vomiting (PONV),
requests for rescue anti-emetic medication, and incidence of side effects were
recorded. The number of symptom-free patients in each group increased as the
droperidol dose increased, but although there was a significant inverse
association between the total dose of droperidol received and the severity of
PONV (P < 0.05), there were no significant differences between individual groups.
In each group, patients were significantly less sedated at 24 h compared with 12
h (P < 0.01). However, after 24 h, patients in group 4 were significantly more
sedated than patients in groups 1 and 2 (P < 0.05). There were no significant
differences between the groups in terms of the incidence of anxiety or other side
effects attributable to droperidol. The present authors suggest that, although
the results demonstrate few statistically significant differences between the
four groups, a PCA bolus dose of droperidol of 0.10 mg mL-1 appears to provide
the optimal balance between anti-emetic efficacy and an acceptable incidence of
side effects.
PMID- 9649990
TI - Comparison of time course of neuromuscular blockade in young children following
rocuronium and atracurium.
AB - In order to compare the neuromuscular effects following rocuronium 0.6 mg kg-1
and atracurium 0.5 mg kg-1 30 children aged from 18 to 67 months were studied
under the same anaesthetic conditions. After induction of anaesthesia with
etomidate and fentanyl, neuromuscular blockade was monitored by recording the
electromyographic response of the adductor pollicis muscle to a supramaximal
train-of-four (TOF) stimulation of the ulnar nerve at 2 Hz for 2 s at 20-s
intervals. Intubation was performed when more than 90% muscle relaxation was
achieved, thereafter anaesthesia was maintained with 70% nitrous oxide in oxygen
and isoflurane 0.5% end-tidal. Mean onset of action was significantly faster
following rocuronium (86 +/- 44.9 s) (mean +/- SD) compared with atracurium
(126.3 +/- 61.0 s). Clinical duration with rocuronium was 22.8 +/- 5.31 min and
thus significantly shorter than that of atracurium, which was 31.5 +/- 6.01 min.
A statistically significant difference between rocuronium and atracurium also had
been found for recovery of T1 to 50%, 75% and 90% as well as for the time taken
to a TOF ratio of 70%. The recovery index for rocuronium and atracurium was not
significantly different with 9.2 +/- 3.43 min and 10.9 +/- 2.65 min,
respectively. Thus, rocuronium may be more advantageous than atracurium for short
lasting surgical procedures in young children.
PMID- 9649991
TI - Checking the anaesthetic machine: self-reported assessment in a university
hospital.
AB - Checking the anaesthetic machine before its daily use is essential. The aim of
our study was to evaluate, through the use of an anonymous questionnaire, how the
anaesthetists of our institution (physicians and nurses) report their daily
checking. Sixty-three questions were used to ask the participants how frequently
they checked the main components of the anaesthetic machine; the answers were
evaluated with a score (0-3). The overall response rate was 78%, nurses; rate
being lower than physicians' rate. Nurses obtained a higher global score, which
raises the question of different adherence to guidelines by nurses and
physicians. Moreover, questions in relation to gas supply were badly scored by
all participants, which should alert us to reinforce theoretical and practical
training in these items. Finally, although the methodology used in this survey
could raise the question of the best way to evaluate the actual checkout
procedure, self-reported assessment remains an alternative to more complex and
expensive methods, such as an observer or a video evaluation.
PMID- 9649992
TI - Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic
maternal-fetal sheep preparation.
AB - A randomized crossover study was designed using the chronically instrumented
pregnant sheep preparation to study the possible effects of epidural injection of
adrenaline as a single compound on the circulation of mother and fetus. Three
consecutive identical doses of adrenaline were administered epidurally with a 30
min interval between treatments. In a randomized crossover fashion two dosages
(10 and 15 micrograms) were tested on different days. The day after the last
epidural experiment the same doses of adrenaline were given intravenously (i.v.).
Between the two i.v. doses a 30 min interval was allowed for values to return to
baseline. Twenty-seven experiments were performed in eight ewes. Epidural
administration of adrenaline did not affect maternal mean arterial pressure,
maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat
rate, or maternal and fetal blood gases and acid-base status. After i.v.
administration of adrenaline the uterine blood flow decreased in a dose-dependent
fashion, but the other haemodynamic variables were not affected. In conclusion,
this study indicates that consecutive epidural injections of adrenaline have no
significant effect on maternal and fetal haemodynamic responses, uterine blood
flow, blood gases and acid-base status in the gravid ewe. However, an i.v.
injection of 10 or 15 micrograms adrenaline decreases the uterine blood flow and
could compromise the fetus.
PMID- 9649993
TI - Adsorption of desflurane from the scavenging system during high-flow and minimal
flow anaesthesia by zeolites.
AB - Application of high-silica zeolites in a special adsorber allows complete
selective adsorption of the inhalation anaesthetic desflurane from the outlet
port of the scavenging system of the anaesthesia machine. In comparison with
charcoal filters, zeolites allow almost complete desorption at moderate
temperatures followed by condensation of the desflurane to the liquid phase. The
adsorption of scavenged desflurane by zeolites was measured in 13 patients. The
duration of the anaesthesia was between 70 and 130 min. A minimal-flow regime
(0.5 L min-1 fresh gas inflow) was used for maintenance in seven patients and a
higher-flow regime (3 L min-1 fresh gas flow) was used for maintenance in six
patients. In minimal-flow anaesthesia, 62% of the delivered desflurane was
adsorbed by the zeolite while 86% of the delivered desflurane was adsorbed in
higher-flow anaesthesia. Preliminary results show that about 85% of the adsorbed
desflurane could be recovered as liquid with high purity via desorption.
PMID- 9649994
TI - Value of oropharyngeal Mallampati classification in predicting difficult
laryngoscopy among obese patients.
AB - The prediction of difficult intubation in obese patients was investigated by co
estimating the degree of visibility of oropharyngeal structures in conjunction
with the respective body mass index. Data were collected prospectively in a
series of 1833 consecutive adult patients. Body mass index (BMI) in kg m-2 was
used as a measure of obesity (morbid: > 40, moderate: 30-40, no obesity: < 30).
The oropharyngeal class findings were assessed using the original methodology as
well as by a modification requiring the tongue to be pulled forward by the
examiner. Difficult intubation was defined as inadequate exposure of the glottis
by direct laryngoscopy. Both oropharyngeal class methodologies were of equal
sensitivity, whereas the modified technique presented a significantly higher
positive predictive value (50.0% vs. 37.2%, P < 0.01). Statistical analysis
revealed an increased risk of difficult laryngoscopy among obese patients
compared with subjects with normal body mass index (20.2% vs. 7.6%, P < 0.001).
When obesity is estimated with respect to oropharyngeal class the positive
predictive value is greatly improved (66.7% vs. 20.2%, P < 0.001). We conclude
that obesity which is associated with a disproportionately large base of the
tongue, is a predisposing factor for difficult laryngoscopy.
PMID- 9649995
TI - Changes in plasma catecholamine concentrations and haemodynamic effects of
rocuronium and vecuronium in elderly patients.
AB - Rocuronium administration may cause tachycardia and an increase in cardiac index.
Pancuronium, another steroidal non-depolarizing muscle relaxant, augments release
of, and blocks re-uptake of catecholamines at adrenergic nerve endings. This
study compared the haemodynamic effects of, and changes in catecholamine
concentrations following administration of vecuronium (0.12 mg kg-1) or
rocuronium (0.9 mg kg-1) to elderly patients. Thirty patients, 65 years or older,
not receiving beta-blockers, were studied. During thiopentone, fentanyl, nitrous
oxide anaesthesia, either rocuronium (0.9 mg kg-1) or vecuronium (0.12 mg kg-1)
was administered, according to random allocation. In all 30 patients, blood
pressure and heart rate were measured before induction of anaesthesia,
immediately and 1 min after induction, 1 and 2 min after muscle relaxant
administration, and immediately, 1 and 2 min after tracheal intubation. In the
latter 20 patients, samples for plasma catecholamine estimation were obtained
prior to, and 1 min after muscle relaxant administration and 1 min after tracheal
intubation. Blood pressure and heart rate were similar in the two groups
throughout the study. Plasma noradrenaline concentrations were similar in the
vecuronium and rocuronium groups prior to muscle relaxant administration
(589(SD240) and 444(SD213) pg mL-1, respectively), 1 min after muscle relaxant
administration (602(SD220) and 520(SD392) pg mL-1, respectively) and 1 min after
tracheal intubation (597(SD351) and 440(SD181) pg mL, respectively). There was no
significant change in either plasma noradrenaline or adrenaline concentrations in
either group following muscle relaxant administration or tracheal intubation. The
use of rocuronium (0.9 mg kg-1) in elderly patients does not result in a
clinically significant change in heart rate, blood pressure or plasma
catecholamine concentration.
PMID- 9649996
TI - Efficacy of thoracic epidural analgesia following laparoscopic cholecystectomy.
AB - This study was undertaken to determine whether epidural analgesia has any benefit
for post-operative pain relief in patients undergoing laparoscopic
cholecystectomy. Patients were randomly assigned to receive post-operative
epidural analgesia with a morphine-bupivacaine combination (Group A, n = 22) or
placebo (saline) (Group B, n = 22). The same standard general anaesthetic
technique, which consists of nitrous oxide and isoflurane in oxygen was used.
Analgesia was assessed using visual analogue pain scores (0-10 cm). The
evaluation was carried out 24 and 48 h post-operatively. At 24 h after
anaesthesia, pain scores in Group A (2.3 +/- 1.2) were lower than those in Group
B (4.4 +/- 1.5) (P < 0.05). However, at 48 h post-operatively, no difference in
scores was observed between the two groups. In conclusion, epidural analgesia
with a morphine-bupivacaine combination improves pain relief during the first 24
h following laparoscopic cholecystectomy.
PMID- 9649997
TI - Changes in adhesion molecule expression and oxidative burst activity of
granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass
compared with abdominal surgery.
AB - Cardiac and major abdominal surgery are associated with granulocytosis in
peripheral blood. The purpose of the present study was to describe the
granulocyte and monocyte oxidative burst and the expression of adhesion molecules
following cardiac surgery with cardiopulmonary bypass and abdominal surgery. The
ability to respond with an oxidative burst was measured by means of flow
cytometry using 123-dihydrorhodamine. The adhesion molecules CD11a/CD18,
CD11c/CD18, CD44 were measured using monoclonal antibodies. Blood samples from
eight patients undergoing open-heart surgery were taken before surgery, 1, 5, 10
and 20 min after aortic clamping, and then 1, 5, 10 and 20 min and 1, 2 and 3 h
after declamping. Samples from eight patients undergoing abdominal surgery were
taken before surgery, at the end of surgery, and 2 and 3 h post-operatively. A
decrease in number of granulocytes and monocytes during cardiopulmonary bypass
was observed. The percentage of CD11a-positive granulocytes increased from 30%
pre-operatively to 75% following cardiopulmonary bypass, while CD44-positive
granulocytes increased from 5% to 13%. Despite the extent of the changes, these
were not significant. The oxidative burst of the granulocytes and monocytes
decreased after declamping to 15% and 27% of initial values in vitro. Several
hours after surgery, there was no significant difference between the two groups.
These results can be explained by a granulocyte and monocyte refractory response
developing subsequent to an increased per-operative oxidative burst activity, and
the induction of adhesion molecules on granulocytes associated with the
cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with
cardiopulmonary bypass was associated with a rapid and pronounced activation of
leukocytes which may play a role in reperfusion injury.
PMID- 9649998
TI - Acute pain services in Europe: a 17-nation survey of 105 hospitals. The EuroPain
Acute Pain Working Party.
AB - A 17-nation survey was undertaken with the aim of studying the availability of
acute pain services (APS) and the use of newer analgesic techniques, such as
epidural and patient-controlled analgesia (PCA). A questionnaire was mailed to
selected anaesthesiologists in 105 European hospitals from 17 countries.
Depending on the population, between five and ten representative hospitals from
each country were selected by a country coordinator. A total of 101 (96.2%)
completed questionnaires were returned. A majority of respondents were
dissatisfied with pain management on surgical wards. Pain management was better
in post-anaesthesia care units (PACUs); however, 27% of participating hospitals
did not have PACUs. There were no organized APS in 64% of hospitals, although
anaesthesiologists from chronic pain centres were available for consultation. In
the hospitals that had APS, the responsible person for the APS was either: (1) a
junior anaesthesiologist (senior anaesthesiologist available for consultation);
or (2) a specially trained nurse (supervised by consultant anaesthesiologists).
Many anaesthesiologists were unable to introduce techniques such as PCA on wards
because of the high equipment costs. Although 40% of hospitals used a visual
analogue scale (VAS) or other methods for assessment of pain intensity, routine
pain assessment and documenting on a vital sign chart was rarely practised. There
was a great variation in routines for opioid prescription and documentation
procedures. Nursing regulations regarding injection of drugs into epidural and
intrathecal catheters also varied considerably between countries. This survey of
105 hospitals from 17 European countries showed that over 50% of
anaesthesiologists were dissatisfied with post-operative pain management on
surgical wards. Only 34% of hospitals had an organized APS, and very few
hospitals used quality assurance measures such as frequent pain assessment and
documentation. There is a need to establish organized APS in most hospitals and
also a need for clearer definition of the role of anaesthesiologists in such APS.
PMID- 9649999
TI - Anaesthetic management for caesarean section combined with removal of
phaeochromocytoma.
AB - In this case report, the anaesthetic management for a removal of
phaeochromocytoma undertaken immediately following Caesarean section is
described. A 32-year-old female patients was given epidural anaesthesia for
Caesarean section, and thereafter, general anaesthesia for a resection of
phaeochromocytoma. During surgery, phentolamine, nitroglycerine and prostaglandin
E1 were electively administered to decrease blood pressure and heart rate. A live
infant was delivered and the supra-adrenal tumour was excised successfully. The
patient's post-operative recovery was uneventful.
PMID- 9650000
TI - Cerebral aneurysm surgery in a patient with phaeochromocytoma.
AB - This case report describes the peri-operative management of a 48-year-old woman
with three cerebral aneurysms and phaeochromocytoma. The pharmacological and
anaesthetic management of such patients is complex, and needs to be managed
carefully by titrating anaesthetic agents and vasoactive drugs. The primary
concern is the maintenance of cerebral perfusion pressure and autoregulation
throughout the procedure, although these states cannot be monitored directly. The
patient survived the operation neurologically intact, and it is presumed that the
course of management which was chosen helped to achieve this result.
PMID- 9650001
TI - Intestinal pseudo-obstruction associated with oral morphine.
AB - Morphine is recommended as the strong opioid of choice by the World Health
Organization (WHO) for cancer pain management. It is associated with delay in
gastro-intestinal transit; as a result, patients may experience marked
constipation. We describe a case of intestinal pseudo-obstruction associated with
the use of oral morphine in a terminally ill cancer patient.
PMID- 9650002
TI - Fatal air embolism: a complication of manipulation of a cavitating metastatic
lesion of the liver.
AB - A patient undergoing emergency laparotomy for an acute abdomen developed fatal
air embolism as a result of surgical manipulation of a cavitating metastatic
lesion of the liver. The diagnosis was made at postmortem examination. This cause
of air embolism has apparently not been reported before. The causes and
management of air embolism are briefly reviewed. It is concluded that in
exceptional circumstances when intubated patients are sent to a recovery area,
the continuation of CO2 monitoring into the post-operative period should be
considered.
PMID- 9650003
TI - Use of the laryngeal mask during emergence from anaesthesia.
PMID- 9650004
TI - Treating severe tetanus with muscle paralysis and intermittent positive pressure
ventilation.
PMID- 9650005
TI - Repeated measures ANOVA for responses developing over time.
PMID- 9650006
TI - Relevance of erythrocyte Na+/Li+ countertransport measurement in essential
hypertension, hyperlipidaemia and diabetic nephropathy: a critical review.
AB - In this review the usefulness of the measurement of erythrocyte Na+/Li+
countertransport (Na+/Li+ CT) activity is evaluated. In particular, the
association between enhanced erythrocyte Na+/Li+ CT activity and essential
hypertension, hyperlipidaemia and diabetic nephropathy is discussed. The
conclusion of this review is that elevated erythrocyte Na+/Li+ CT activity is
associated with essential hypertension and hyperlipidaemia. A relationship
between Na+/Li+ CT activity and diabetic nephropathy is less evident. Despite a
significant link of Na+/Li+ CT activity with hypertension and hyperlipidaemia,
the diagnostic significance of Na+/Li+ CT activity is low. This is due to the
large overlap between the results of control subjects and patients. The factors
that contribute to this broad range are discussed in detail.
PMID- 9650007
TI - Effects of parathyroid hormone and serum calcium on the phenotype and function of
mononuclear cells in patients with primary hyperparathyroidism.
AB - BACKGROUND: Several studies have demonstrated specific influence of parathyroid
hormone (PTH) on immune parameters, especially on T- and B-cell function,
migration of polymorphonuclear leucocytes (PMNLs) and antibody synthesis, in
patients with secondary hyperparathyroidism and chronic renal failure and
recently also in patients with primary hyperparathyroidism (pHPT). METHODS: We
therefore examined 12 patients with pHPT before and 6 months after
parathyroidectomy (PTX) and nine sex- and age-matched control subjects to
determine the impact of PTH and serum calcium concentrations on several immune
parameters, including (a) serum concentrations of immunoglobulins, (b)
immunophenotype of peripheral blood lymphocytes, (c) phytohaemagglutinin (PHA)
induced lymphocyte proliferation and (d) monocytic surface marker expression.
RESULTS: Serum concentrations of immunoglobulins (IgG, IgA, IgM) were unaffected
by elevated serum PTH and calcium levels. T lymphocytes (CD3), B lymphocytes
(CD19), NK cells (CD16/56) and monocytes (CD16) revealed a normal distribution
and were not different before and after PTX in patients with pHPT when compared
with the control group. CD4+ T-helper lymphocytes were significantly elevated pre
and post-operatively in patients with pHPT. The lymphocyte proliferation
response to PHA in the highest concentration (12.5 micrograms L-1) tested was
significantly suppressed in patients with pHPT preoperatively when compared with
the patients post-operatively and the control group. In addition, both CD4+ and
CD8+ lymphocytes showed a lower expression of activation markers, interleukin 2
(IL-2) receptor (CD25) and transferrin receptor (CD71), which could be partially
restored 6 months after PTX, but did not reach normal values. CONCLUSION: In
summary, in contrast to the findings in patients with secondary HPT, pHPT appears
to be associated with less alterations of immune functions. Chronically elevated
serum PTH and calcium concentrations in patients with pHPT induce a higher
percentage of CD4+ helper T lymphocytes and a suppressed lymphocyte response to
PHA as well as a reduced expression of activation markers on peripheral blood
lymphocytes.
PMID- 9650008
TI - Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant
women: effects on serum cholestanol and other non-cholesterol sterols.
AB - BACKGROUND: Our aim was to investigate whether intestinal binding of bile acids
by guar gum, a dietary fibre, relieves cholestasis and pruritus in intrahepatic
cholestasis of pregnancy. METHODS: Forty-eight pregnant women with cholestasis
and pruritus were randomized double-blind to guar gum and placebo until the time
of delivery, and 20 healthy pregnant women were used as control subjects. The
pruritus score and serum bile acids, lipids and non-cholesterol sterols were
measured at baseline, at least 2 weeks after treatment, just before delivery and
up to 4 weeks after delivery. RESULTS: The increase in serum bile acids and
worsening of pruritus were prevented by guar gum in relation to placebo (P <
0.05). Serum cholesterol was unchanged, but increased cholesterol precursor
sterol values suggested that cholesterol synthesis was increased by guar gum.
Serum cholestanol proportion, an indicator of cholestasis, was related to
pruritus but was unaffected by guar gum. CONCLUSION: We conclude that in
intrahepatic cholestasis of pregnancy and pruritus, guar gum treatment is
beneficial in relieving pruritus, even although indicators of cholestasis are
only partially reduced.
PMID- 9650009
TI - Cellular and molecular characteristics of inflammation in chronic bronchitis.
AB - METHODS: To examine the inflammatory process in chronic bronchitis, we evaluated
the cell and cytokine profile in bronchoalveolar lavage fluid from 12 chronic
bronchitis patients who smoked, six chronic bronchitis patients who did not
smoke, 10 subjects control subjects without pulmonary diseases who smoked and
eight control subjects who did not smoke. RESULTS: Chronic bronchitis patients
who smoked had increased numbers of macrophages, neutrophils, eosinophils, mast
cells and activated CD8+ T lymphocytes and predominantly expressed interleukin-8,
tumour necrosis factor alpha and interleukin-2 genes and proteins. The number of
macrophages and neutrophils and the expression of interleukin 8 were also
increased in control subjects who smoked compared with healthy subjects who did
not smoke. Chronic bronchitis patients who did not smoke had increased numbers of
eosinophils, mast cells and activated CD4+ T lymphocytes and predominantly
expressed interleukin-5 and granulocyte-macrophage colony-stimulating factor
genes and proteins. CONCLUSION: Thus, the cellular and molecular characteristics
of the inflammatory process in chronic bronchitis patients who smoke and do not
smoke are different, suggesting a different pathogenesis of the disease.
PMID- 9650010
TI - Expression of tenascin is related to angiogenesis in pre-eclampsia.
AB - METHODS: Ten samples of decidua basalis from pre-eclamptic women and 10 from
healthy primigravid women subjected to caesarean section (control tissues) were
investigated immunohistochemically for changes in angiogenesis and expression of
tenascin, an extracellular matrix protein thought to modulate angiogenesis. In
addition, pre-eclamptic and control samples were grafted onto the chick embryo
chorioallantoic membrane (CAM) to study their possible angiogenic activity in
vivo. RESULTS: Although the microvessel area was low in control samples, it
increased significantly in the pre-eclamptic decidua. In parallel, the area
covered by tenascin staining underwent a significant expansion that was highly
correlated with the microvessel area. Angiogenic activity was assessed both
macroscopically and microscopically on histological sections 4 days after
grafting. In contrast to control samples, pre-eclamptic decidua induced an
intense capillary growth, and numerous capillaries converging towards the implant
and forming a spoke-wheel pattern were evident. Histological examination using a
planimetric point-count method showed that microvessel counts in the CAM area
under and around the pre-eclamptic implants were significantly higher than those
of control samples. Again, the extracellular matrix of nearby microvessels was
strongly immunoreactive with tenascin. CONCLUSION: It is suggested that, unlike
normal decidua, pre-eclamptic decidua displays an intense, autonomous angiogenic
activity, probably mediated by tenascin in addition to its own angiogenic
factors.
PMID- 9650011
TI - Accumulation of chylomicron remnants in homozygous subjects with familial
hypercholesterolaemia.
AB - BACKGROUND: Post-prandial lipoprotein kinetics were investigated in subjects who
lack functioning low-density lipoprotein (LDL) receptors [homozygous familial
hypercholesterolaemia (FH)]. METHODS: An oral fat load was given, and chylomicron
plasma kinetics was determined by monitoring the clearance of triglyceride,
retinyl palmitate and apolipoprotein B48, calculated as the area under the curve,
for 7.5 h. In addition, the binding and uptake of chylomicron remnants by
fibroblasts of FH and control subjects were assessed in vitro. RESULTS: Based on
the plasma kinetics of chylomicron triglyceride, retinyl palmitate and
apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be
substantially delayed compared with normolipidaemic control subjects. Consistent
with involvement of the LDL receptor in chylomicron clearance, binding and uptake
of chylomicron remnants by fibroblasts of FH subjects was found to be
substantially less than in cells from control subjects. CONCLUSION: This study
shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH
and that the LDL receptor is significantly involved in the clearance of post
prandial lipoproteins. Moreover, this study raises the possibility that in FH,
and in other disorders in which LDL receptor expression is reduced, atherogenesis
might be a post-prandial disease.
PMID- 9650012
TI - Lack of relationship between the P1A1/P1A2 polymorphism of platelet glycoprotein
IIIa and premature myocardial infarction.
AB - BACKGROUND: The P1A1/P1A2 polymorphism of the platelet glycoprotein IIIa has been
variably associated with an increased risk of coronary thrombosis. MATERIALS: We
investigated the linkage between the P1A1/P1A2 polymorphism and the risk of
myocardial infarction in 98 patients who suffered their first myocardial
infarction at the age of 45 years or less and 98 well-matched control subjects
without coronary artery disease. Lipid parameters were measured using
conventional methods of clinical chemistry; P1A genotypes were determined by
polymerase chain reaction and restriction enzyme digestion. RESULTS: There was no
significant difference in the prevalence of P1A2-positive genotypes (either
P1A1/P1A2 or P1A2/P1A2) between patients and control subjects (chi 2 = 0.66, d.f.
= 1, P = 0.41). CONCLUSIONS: These results suggest that the P1A2 polymorphism of
the platelet glycoprotein IIIa does not contribute to the genetic susceptibility
to premature myocardial infarction.
PMID- 9650013
TI - Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected
patients: a randomized, controlled pilot study.
AB - BACKGROUND: The aim of this work was to study the effects of combined oral
administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma
glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human
immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective,
randomized and controlled therapy trial with partial crossover. Twenty-four
antiretroviral-naive HIV-infected outpatients at Centers for Disease Control
(CDC)'93 stages I and II were randomized to receive the antioxidant combination
NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n =
13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus,
group B served as untreated control during the first 12 weeks. RESULTS: There was
(a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6
weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P =
0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38
count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033
respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared
with the control period of group B. The effects observed in group A were,
however, not paralleled to the same extent by group B after crossing-over to
treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH
Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the
reduced/total GSH ratio were not affected by the treatment. Serum selenium levels
increased significantly (P < 0.001) upon treatment. Viral load was not altered.
CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not
comparable to those after standard antiretroviral drug therapy. This, however,
does not preclude per se possible benefits of antioxidant supplementation in HIV
disease.
PMID- 9650014
TI - Growth effects of alpha-interferon but not of bombesin or angiotensin II are
mediated by activation of STAT proteins.
AB - BACKGROUND: The recently discovered Jak/STAT signal transduction pathway is
associated with cytokine or growth factor receptors; whether members of the G
protein-coupled receptor superfamily also activate this pathway is not yet clear.
As a first member, the angiotensin (AT)1A receptor has been demonstrated to
phosphorylate Jak and STAT proteins. Bombesin, a neurotransmitter and growth
factor in many cells and tissues, activates its G protein-coupled receptor and in
addition phosphorylates proteins that might be members of the Jak/STAT family.
This study investigated whether bombesin- or angiotensin-mediated growth effects
are associated with STAT protein activation. METHODS: Functional receptors were
characterized using ligand-binding studies, second-messenger activation and
determination of ligand-mediated growth effects. STAT protein activation was
analysed by electrophoretic mobility shift assay (EMSA) using labelled DNA
response elements recognizing all known STAT proteins. RESULTS: Functional
bombesin receptors mediating mitogenic effects were demonstrated on Swiss 3T3
fibroblasts, human melanoma cells (A375-6) and primary human lung fibroblasts;
however, bombesin-related STAT protein activation was not observed by EMSA.
Interferon-alpha typically activated a STAT1-STAT2-p48 heterotrimer, as well as
STAT1-3 hetero- and homodimers in human melanoma cells and significantly
inhibited growth of this cell line in vitro. Functional AT1A receptors on primary
rat cardiac fibroblasts mediated angiotensin-stimulated growth effects but, in
contrast to recently published data, did not activate any known STAT protein.
CONCLUSION: Interferon alpha-stimulated growth inhibition is mediated by
activation of the Jak/STAT pathway, whereas bombesin or AT1A receptor-mediated
effects on cellular proliferation do not involve phosphorylation of STAT
proteins.
PMID- 9650015
TI - Comparison of three fatty meals in healthy normolipidaemic men: high post
prandial retinyl ester response to soybean oil.
AB - BACKGROUND: Oral fat tolerance tests (FTTs) have been widely used as a tool to
investigate post-prandial lipaemia. However, there is no consensus regarding the
type and amount of fat used in the tests. METHODS: We compared three commonly
used FTTs, each containing 63 g of fat: a mixed meal, a liquid cream meal and a
liquid soybean oil meal. The study group consisted of 10 healthy normolipidaemic
men. We measured triglycerides (TGs), retinyl esters (REs), apolipoprotein E
(apoE), apolipoprotein B-48 (apoB-48) and apolipoprotein B-100 (apoB-100) in
plasma and in triglyceride-rich lipoprotein (TRL) fractions separated by density
gradient ultracentrifugation at baseline and 3, 4, 6, and 8 h after the FTTs.
RESULTS: We observed similar TGs, apoE, apoB-48 and apoB-100 responses after all
three FTTs, despite the different fatty acid composition of the meals. In
contrast, the commonly used marker for exogenous particles, RE, differed clearly
when polyunsaturated (soybean oil) and saturated fat (cream or mixed meal) were
used. The RE response in plasma (P < 0.005, repeated measures ANOVA), in
chylomicrons (P < 0.013) and in very low-density lipoprotein (VLDL) 1 (P <
0.017), as well as the RE area under the incremental curve in plasma and
chylomicron fractions, were markedly increased after the soybean oil meal
compared with the mixed meal and cream meal tests. The peak of RE response
occurred parallel to the responses of other markers (i.e. TG or apoB-48) of post
prandial TRL during soybean oil meal. In contrast, RE peak concentration was
delayed after saturated fat-containing meals. After soybean oil, FTT plasma
cholesterol concentration was lower and the chylomicron cholesterol concentration
was higher compared with mixed or cream meals, but no differences were detected
in post-prandial high-density lipoprotein (HDL)-cholesterol concentration.
CONCLUSION: When the amount of fat is similar, post-prandial responses of TG,
apoE, apoB-48, apoB-100 and HDL-cholesterol were comparable after different FTTs.
PMID- 9650016
TI - Expression of cGMP-dependent protein kinase I and its substrate VASP in
neointimal cells of the injured rat carotid artery.
AB - BACKGROUND: Neointimal fibroproliferative lesions after balloon angioplasty
remain a major clinical problem, frequently leading to restenosis of initially
successfully dilated coronary arteries. The cGMP-dependent protein kinase type I
(cGMP-PK I) and its substrate vasodilator-stimulated phosphoprotein (VASP),
molecular targets of the atrial natriuretic factor (ANF) and nitric oxide (NO)
signalling pathways, are likely to be involved in various aspects of vascular
wall regulation and restenosis formation. METHODS: To investigate the occurrence
of cGMP-PK I and VASP in neointimal cells in situ, we performed
immunohistochemistry and immunoblotting experiments on denuded rat carotid
arteries. RESULTS: Although the soluble cGMP-PK I showed a homogeneous
distribution throughout the neointima, VASP apparently was more concentrated in
smooth muscle cells (SMCs) lining the artery lumen, possibly reflecting enhanced
growth factor stimulation of luminal SMCs. The membrane-associated cGMP-PK type
II could not be detected in both the non-injured vessel wall and the restenotic
tissue. CONCLUSION: The presence of both cGMP-PK I and VASP, major regulators of
the actin cytoskeleton and cell motility, in neointimal tissue suggest that this
emerging signal transduction pathway could be a target for the regulation and
control of restenosis.
PMID- 9650017
TI - Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial
cell line.
AB - BACKGROUND: Pneumocystis carinii (PC) infection often results in severe pneumonia
in immunocompromised patients. Attachment of PC organisms to alveolar epithelial
cells is a hallmark of PC pneumonia; however, few studies have investigated the
response of alveolar epithelial cells to PC infection. METHODS: Interleukin 6 (IL
6) is a multifunctional cytokine that is produced by alveolar epithelial cells in
response to a variety of stimuli. Our investigation was undertaken to determine
whether PC organisms induce production of IL-6 by alveolar epithelial cells and
to determine the effect of IL-6 on PC attachment. RESULTS: Incubation of the
human alveolar epithelial cell line, A549, with PC organisms resulted in a
significant increase in IL-6 secreted into the cell culture media. Time-course
studies showed that IL-6 production was detected as soon as 2 h after addition of
PC and continued up to 48 h of exposure. Further studies demonstrated that
preincubation of A549 cells with IL-6 resulted in a concentration-dependent
increase in both A549 cell production of fibronectin and PC attachment.
CONCLUSION: Thus, PC attachment to an alveolar epithelial cell line results in
epithelial cell production of IL-6, which can act to further increase PC
attachment. This may provide an important mechanism whereby PC organisms directly
affect the host response to PC infection.
PMID- 9650018
TI - Intestinal epithelial hyperpermeability. Mechanisms and relevance to disease.
AB - Pathologic increases in intestinal permeability to hydrophilic macromolecules has
been identified in a number of clinical conditions. The significance of gut
barrier dysfunction as a clinical issue remains to be delineated, although it
seems likely that alterations in intestinal epithelial permeability play a
causative role in a number of conditions ranging from inflammatory bowel disease
to the development of complications after cardiopulmonary bypass. It is unlikely
that any one mechanism can account for all cases of intestinal hyperpermeability.
Rather, it is more probable that myriad factors or combinations of factors,
including mesenteric ischemia and cytokine-induced phenomena, lead to alterations
in permeability in different clinical entities. Nevertheless, from a purely
mechanistic standpoint, some common themes, notably the role of ATP depletion,
increases in [Ca2+]i, and cytoskeletal derangements in enterocytes, have emerged
as being particularly important.
PMID- 9650019
TI - The aging gut. Nutritional issues.
AB - With improvements in health care, living standards, and socioeconomic status,
more adults are living to old age. As the population ages, it is increasingly
important to understand the factors that affect the nutritional status and thus
the health status of older adults. Many factors contribute to inadequate
nutrition, including health status, financial capacities, mobility, exercise, and
physiologic needs. This article considered only the potential changes in
nutritional needs because of alterations in the gastrointestinal tract owing to
aging. One of the most remarkable changes with aging is the frequent development
of atrophic gastritis and the inability to secrete gastric acid. This process
affects approximately a third of older adults in the United States and only
recently was recognized to be due to infection by H. pylori in the majority of
cases. The lack of gastric acid in atrophic gastritis may lead to small
intestinal bacterial overgrowth and influences the absorption of a variety of
micronutrients, including iron, folate, calcium, vitamin K, and vitamin B12.
Lactose maldigestion is a frequent condition in older adults and is extremely
common worldwide. The intolerance of dairy products leads to avoidance of these
foods and likely contributes to the development of osteopenia. Overall, the small
intestine and pancreas undergo astonishingly few clinically significant changes
with aging. The relative preservation of overall gastrointestinal function with
aging is likely due to the large reserve capacity of this multiorgan system.
Further research is needed to define the precise nutritional needs for older
adults because simple extrapolation of values from younger adults is now
recognized to be insufficient. In addition, it is no longer acceptable to define
adequate nutriture in terms of amounts of vitamins needed to maintain serum
levels of a nutrient. Further RDAs must consider the functional implications of
adequate nutrition. Nutrients in the elderly will be measured as to whether they
result in improvements in markers of chronic disease such as homocysteine or,
most importantly, in the prevention of chronic disease such as osteoporosis and
cardiovascular disease.
PMID- 9650020
TI - Diet, nutrients, and gastrointestinal cancer.
AB - Tobacco and alcohol use are strong risk factors for cancer of the upper
gastrointestinal tract. Saturated fat and red meat intake also appear to increase
the risk of colorectal cancer. The strongest and most consistent dietary
protective factors for gastrointestinal cancer are vegetables and fruits. Some
micronutrients show beneficial effects, but the degree of protection is less than
that observed from whole plant foods. Substantial decreases in the morbidity and
mortality from gastrointestinal cancer could occur with more widespread adoption
of dietary guidelines designed for cancer prevention.
PMID- 9650021
TI - Nutritional assessment.
AB - Nutritional status is a dynamic entity that changes because of interactions
between nutrient intake and absorption and requirements and disease. Clinically
relevant nutritional assessment should determine whether the patient's
nutritional status will decline in the absence of nutritional support. In
addition, such assessment should predict complications in the absence of
nutritional intervention. The role of different techniques--clinical body
compositional, and functional--is discussed in this context.
PMID- 9650022
TI - Enteral nutrition.
AB - This article briefly reviews the literature supporting the use of enteral
nutrition, which appears to be the preferred method of nutritional support in
critically ill patients. Patients who benefit the most from this type of support,
as well as the administration and route preferences in enteral nutrition, are
discussed. In addition, the different types of enteral formulas and the more
frequently associated complications that occur with tube feedings are reviewed.
PMID- 9650023
TI - Nutrient pharmacotherapy for gut mucosal diseases.
AB - The use of nutrients for pharmacotherapy is a recent advance in the treatment of
gastrointestinal disorders or alterations of gut function and structure.
Nutrients may have a direct effect on the gut, or may enhance the response to
medications. Alternatively, pharmacologic agents may improve the absorption of
nutrients. Potentially, pharmacotherapy may be an adjunct to the traditional
approach used in the treatment of compromised patients.
PMID- 9650024
TI - Nutrient antioxidants in gastrointestinal diseases.
AB - Oxidative stress appears to play a role in the pathogenesis of a number of
gastrointestinal disease states, including pancreatitis; gastric and duodenal
ulcer disease; IBD; gastric, esophageal, and colon cancers; and hepatic injury
secondary to alcohol, metal storage disorders, hepatitis, and
ischemia/reperfusion injury. The nutritional antioxidants are attractive
potential therapeutic and chemopreventive agents because they are inexpensive and
have a relatively low toxicity profile. A word of caution should be noted: Some
antioxidants, such as vitamin C, can be prooxidant under certain conditions, and
systemically altering the redox state may have untoward effects on the
inflammatory response in certain disease states. Thus, at the current time,
antioxidant therapy should be restricted to randomized, controlled clinical
trials, in which treatment effects can be closely monitored, and therapeutic
efficacy can be determined with scientific accuracy.
PMID- 9650025
TI - Nutritional management in acute and chronic pancreatitis.
AB - Patients with severe pancreatitis, characterized by multiple organ failure and
pancreatic necrosis on CT scan (identified by an Acute Physiology and Chronic
Health Evaluation II score of > or = 10 with > or = 3 Ranson criteria), most
likely require aggressive nutritional support. Use of the enteral route of
feeding may help contain the hypermetabolic stress response, reduce morphologic
change and atrophy of the gut, and theoretically decrease late complications of
nosocomial infection and organ failure. Evidence that decreasing degrees of
stimulation of the pancreas occur as the site of feeding descends in the
gastrointestinal tract and evidence from perspective, randomized trials suggest
that jejunal feeding appears at least as safe and well tolerated as total
parenteral nutrition in acute pancreatitis.
PMID- 9650026
TI - Nutritional issues in inflammatory bowel disease.
AB - Malnutrition is a very common problem in patients with chronic inflammatory bowel
diseases. This article discusses the incidence, causes, and clinical consequences
of malnutrition in these patient groups. The role of nutritional support
administered enterally or parenterally either as primary or adjunctive therapy is
highlighted, based on past and more recent controlled studies. Additional
attention is given to the roles of glutamine, short-chain fatty acids, fish oil,
and alternative nutritional therapy.
PMID- 9650027
TI - New clinical issues in celiac disease.
AB - Celiac disease is a chronic disorder of gluten sensitivity associated with a
spectrum of mucosal lesions termed preinfiltrative, infiltrative, hyperplastic,
destructive, and atrophic. The symptoms are not related to the degree of mucosal
pathology but to the extent of the mucosal lesion. Neoplasms constitute the major
complication of celiac disease, and EATCL is the most common neoplasm in this
category. There is evidence that a strict gluten-free diet is protective against
the complications of celiac disease; hence it is important that even the
subclinical forms be diagnosed early. Small bowel biopsy remains the gold
standard for diagnosis of celiac disease; however, antibody tests are a useful
adjunct in deciding whom to biopsy and for screening groups at high risk before
initiating a lifelong gluten-free diet.
PMID- 9650028
TI - Short bowel syndrome.
AB - This article discusses the causes, prognosis, and management of short bowel
syndrome. Attempts to enhance intestinal adaptation with trophic factors and
surgical treatment options, including small bowel transplantation, are discussed.
PMID- 9650029
TI - Home parenteral nutrition. 25 years later.
AB - After 25 years, there is enough clinical outcome experience to determine
appropriate use of home parenteral nutrition in different disease states and age
groups. Information regarding how to avoid complications and how patients and
families can find necessary psychosocial support is provided in this article.
Currently, small bowel transplantation is not a safer choice, unless there is
severe liver disease caused by home parenteral nutrition or lack of central
intervenous access.
PMID- 9650030
TI - Metabolic bone disease in gut diseases.
AB - A wide spectrum of gastrointestinal illnesses impairs bone health and can result
in bone pain, demineralization, and fracture. This article summarizes current
knowledge of the skeletal pathology exhibited in patients with diseases of the
liver, biliary tree, pancreas, and bowel. Mechanisms responsible for these
syndromes and treatment options are discussed. This article enhances the
practicing gastroenterologist's knowledge of the implications of gastrointestinal
illness for bone.
PMID- 9650031
TI - Adjustment disorder: a multisite study of its utilization and interventions in
the consultation-liaison psychiatry setting.
AB - The consultation-liaison (C-L) psychiatry services of seven university teaching
hospitals in the United States, Canada, and Australia (the MICRO-CARES
Consortium) used a common clinical database to examine 1039 consecutive
referrals. A diagnosis of adjustment disorder (AD) was made in 125 patients
(12.0%); as the sole diagnosis, in 81 (7.8%); and comorbidly with other Axis I
and II diagnoses in 44 (4.2%). It had been considered as a rule-out diagnosis in
a further 110 (10.6%). AD with depressed mood, anxious mood, or mixed emotions
were the commonest subcategories used. AD was diagnosed comorbidly most
frequently with personality disorder and organic mental disorder. Sixty-seven
patients (6.4%) were assigned a V code diagnosis only. Patients with AD were
referred significantly more often for problems of anxiety, coping, and
depression; had less past psychiatric illness; and were rated as functioning
better--all consistent with the construct of AD as a maladaptation to a
psychosocial stressor. Interventions were similar to those for other Axis I and
II diagnoses, in particular, the prescription of antidepressants. Patients with
AD required a similar amount of clinical time and resident supervision. It is
concluded that AD is an important and time-consuming diagnostic category in C-L
psychiatry practice.
PMID- 9650032
TI - Risks for oral health with the use of antidepressants.
AB - In this article, attention is focused on oral pathology, particularly dental
caries, caused by hyposalivation as a consequence of (long-term) use of
antidepressants. Changes in clinical psychiatric practice and increasing numbers
of prescriptions of antidepressants in primary care and specialty care settings
have made awareness of this risk even more relevant than in the past. Normal
physiology of salivary glands and changes in the secretion of saliva during use
of antidepressants are described. Monitoring, prevention, and treatment of
hyposalivation induced by antidepressants are encouraged as an adjunct in the
clinical management of depression.
PMID- 9650033
TI - DSM-IV hypochondriasis in primary care.
AB - The object of this study was to assess the prevalence and correlates of the DSM
IV diagnosis of hypochondriasis in a primary care setting. A large sample (N =
1456) of primary care users was given a structured interview to make diagnoses of
mood, anxiety, and somatoform disorders and estimate levels of disability. The
prevalence of hypochondriasis (DSM-IV) was about 3%. Patients with this disorder
had higher levels of medically unexplained symptoms (abridged somatization) and
were more impaired in their physical functioning than patients without the
disorder. Of the various psychopathologies examined, major depressive syndromes
were the most frequent among patients with hypochondriasis. Interestingly, unlike
somatization disorder, hypochondriasis was not related to any demographic factor.
Hypochondriasis is a relatively rare condition in primary care that is largely
separable from somatization disorder but seems closely intertwined with the more
severe depressive syndromes.
PMID- 9650034
TI - How C-L services can comply with new HCFA guidelines.
AB - A psychiatric consultation report form was developed to efficiently and
accurately meet the stringent Medicare documentation guidelines that go into
effect July 8, 1998. This form was designed for use in academic institutions
where the consultation team includes teaching physicians, psychiatric residents,
and medical students. Medicare has strict requirements regarding who may document
each element of the consultation for billing purposes. These requirements were
taken into account in the design of this form. Two academic consultation-liaison
psychiatric services piloted the form and conducted internal audits to evaluate
its usefulness. The accuracy of billing improved twofold at one site because the
form facilitated rapid completion of details requisite to justify CPT codes of
complex assessments. This saved considerable time and effort over the previous
methods used to determine an appropriate level of billing. Critical information
was documented more frequently, thereby meeting the documentation requirements
more consistently. Instructions for use, criticisms, and cautions are given.
PMID- 9650035
TI - Recovery and relapse in geriatric depression after treatment with antidepressants
and ECT in a medical-psychiatric population.
AB - The objective of this naturalistic, longitudinal treatment outcome study was to
determine relapse rates in geriatric depression following treatment with
antidepressants and electroconvulsive therapy in a medical-psychiatric
population. Thirty-nine elderly patients (average age 71 years) with unipolar
major depression were treated with either antidepressants (AD) or, if resistant
to AD treatment, ECT followed by maintenance antidepressants. Patients were
monitored over 18 months, and relapse rates were closely determined using the
Longitudinal Interval Follow-up Evaluation (LIFE) and the 21-item Hamilton
Depression Rating Scale. Although 90% of patients recovered from their index
episode of depression, relapse rates were approximately 29%. These results
indicate that in spite of high chances of recovery from geriatric depression,
intensive psychopharmacologic and psychotherapeutic strategies are needed to
decrease relapse rates in geriatric depression.
PMID- 9650036
TI - Referral patterns and recognition of depression among African-American and
Caucasian patients.
AB - A retrospective review of psychiatric consultations was conducted for African
American and Caucasian patients for a 2-year period. Reasons for referral,
assigned diagnoses, accuracy rates, and discordance and concordance rates were
assessed. Referrals for depression comprised 24.6% of all consults for Caucasian
and African-American inpatients. Only 40.3% of patients referred for depression
were diagnosed with a depressive disorder; 54.4% of patients diagnosed with
depressive disorders were referred for other reasons. African-American patients
were referred for evaluation of depression and diagnosed with depressive
disorders significantly less often than Caucasian patients. No significant
differences were obtained between African-Americans and Caucasians in the
accuracy rates of patients referred for depression. Discordance and concordance
rates for the two groups were comparable. Diagnoses assigned to African-Americans
and Caucasians incorrectly referred for depression did not differ significantly.
For depressed African-Americans and Caucasians referred for reasons other than
depression, the only difference noted was in the referral rates for adjustment of
psychotropics. The nonpsychiatric staff fails to recognize depression and often
refer depressed patients inappropriately. Depressed patients are primarily
referred for suicide assessment and disruptive behaviors. Referrals for
depression may be a secondary concern to nonpsychiatric staff. In addition,
cultural variables and racial differences between hospital staff and patients may
account for the differences in referral patterns. Awareness of the needs of
African-American patients is required.
PMID- 9650037
TI - The contribution of cognitive impairment, medical burden, and psychopathology to
the functional status of geriatric psychiatric inpatients.
AB - In order to define the contributions of cognitive impairment, medical burden, and
psychopathology to the functional status of geriatric psychiatric patients, a
forward-looking, retrospective study of 106 consecutive admissions to a geriatric
psychiatric unit at the Houston Veterans Affairs Medical Center Hospital was
done. It was found that psychopathology and cognitive status, but not medical
burden, contributed to the variance in functional status of geriatric psychiatric
inpatients for both admission scores and for changes in scores during
hospitalization. Improvements in cognitive state and psychopathology were
associated with improvements in functional status during hospitalization.
PMID- 9650038
TI - Psychotherapy with a woman at high risk for developing breast cancer.
AB - Women who are at high risk for developing breast cancer increasingly consult with
psychiatrists about the psychological, social, and sexual consequences of genetic
testing and risk-reducing surgeries such as bilateral mastectomy and
oophorectomy. The 9-year psychotherapy with a woman who had bilateral mastectomy
because of her family history of breast cancer and who later tested negative for
BRCA1 is described and discussed.
PMID- 9650039
TI - Psychiatric morbidity in a series of patients referred from a trauma service.
AB - We studied the clinical characteristics of trauma patients referred to psychiatry
to determine whether these patients differ from the total trauma population. A
chart review of trauma cases referred to psychiatry at our setting in 1995 (N =
60) was compared with all 609 trauma admissions from the same period. The most
common reasons for referral were suicide attempts and depression. The most common
diagnosis was mood disorders (28%). The patients required an average 5.1 follow
up visits. The psychiatric referral group had twice the length of stay.
Psychiatric illness is relatively common in trauma patients and impacts on
psychiatric service resources and length of hospital stay.
PMID- 9650040
TI - Isolated systolic hypertension in the elderly--what's next?
PMID- 9650041
TI - Is the decline in renal function with normal aging inevitable?
AB - The structural changes observed in the normal aging kidney support a concept that
one should expect a decline in renal function as one ages. Reports by renal
physiologists, however, suggest that this is not always true. The suggestion is
made that vascular adaptations to structural changes may help to preserve
glomerular filtration rate by producing a state of hyperperfusion and
hyperfiltration in surviving nephrons.
PMID- 9650042
TI - The controversy surrounding cholesterol treatment in older people.
AB - The evidence of the benefit of lowering cholesterol levels in seniors from
epidemiologic studies and RCTs is conflicting. Epidemiologic studies suggest that
elevated cholesterol levels in elderly people may be a marker of good health. In
some cases, lowering cholesterol in seniors may even prove harmful. Conversely,
RCTs of lipid-lowering therapy have shown clear benefits in reducing coronary
events in younger and middle-aged adults with or without pre-existing CAD. Both
the epidemiologic studies and the RCTs we evaluated have methodologic concerns
that make generalization to all seniors difficult. One epidemiologic study, in
fact, found that there may be a physiologic decline in cholesterol levels as
people age into their 70s and beyond [16]. We still do not appear to have a clear
insight into the precise role cholesterol plays in seniors, especially those over
the age of 75. In the future, as more data becomes available from RCTs and meta
analyses evaluating seniors in the older age group [15], we hope to have a better
understanding of how to treat hypercholesterolaemia in this population. Until
further studies are published, treatment plans need to be individualized, and the
risks and benefits of treatment on various outcomes must be weighed according to
the best evidence we have available.
PMID- 9650043
TI - The treatment choice of elderly patients with erectile dysfunction.
AB - The aim of this study was to determine treatment preference, commitment to choice
of therapy, and the influence of physical disability on treatment choice in a
geriatric group of males with erectile dysfunction (E.D.) of various etiologies.
Eighty-nine patients aged 65 to 83 years (mean 69.5 years) were assessed and
followed at our erectile dysfunction clinic from July 1991 to September 1996.
Etiology of ED was based on clinical assessment. Available treatment options
included oral medications, vacuum devices, injection therapy, penile prostheses,
sex counseling and testosterone when indicated. Median follow-up since initial
consultation was 9 months (range 1 to 63 months). Data was retrieved in a
retrospective fashion from chart review and selective telephone follow-up.
Clinical assessment yielded the following distribution of etiologies:
vasculogenic (57.2%), neurogenic (7.9%), hormonal (1.1%), psychogenic (2.2%), and
multifactorial (32.6%). The most popular initial treatment choices were injection
therapy (30.3%), vacuum device (27.0%), and oral medication (20.2%). Of the 84
patients who chose to be treated, 34 (40.5%) elected to switch to a different
form of therapy after a median time of 7.5 months (range 1 week to 63 months).
Five patients tried a third form of therapy and two proceeded to a fourth. The
remaining patients have continued with their original choice for a median time of
7 months (range 1 to 63 months). A greater drop-out rate (78%) amongst those who
initially chose oral medication was statistically significant when compared to
drop-out rates for injection therapy (48%) and vacuum devices (29%), p = 0.044
and p = 0.005, respectively. Significant physical disabilities in eight patients
did not appear to influence their treatment selection. In conclusion, the elderly
are a unique group of patients who are more likely to have an organic etiology to
their erectile dysfunction. When they do present with erectile dysfunction, they
are inclined to pursue treatment. The choices made by this group of men did not
differ from impotent men in general. When unsatisfied with one form of therapy
they were inclined to pursue an alternative treatment. A significant physical
disability did not preclude a therapeutic choice.
PMID- 9650045
TI - Frequency urgency syndrome following urinary bladder suspension.
AB - Bladder suspension for urinary incontinence secondary to bladder neck
hypermobility is highly successful. Of those who fail, however, a subset will
develop new onset or markedly worsened irritative voiding symptoms. A series of
such patients were identified to study the associated urodynamic abnormalities of
this symptom complex. The charts of female patients presenting for incontinence
from 1992-94 were reviewed. Forty-six patients with a mean age of 59.4 (range 28
79) fulfilled the inclusion criteria of developing new onset or markedly worsened
post-operative frequency, urgency and urge incontinence within two years of
undergoing bladder suspension. All had been evaluated with thorough history,
physical examination, and urodynamic testing. Seventeen patients were found to
have recurrent hypermobility. Eighteen had a diagnosis of intrinsic sphincter
deficiency (ISD), including six that also had another diagnosis. Four patients
were diagnosed with detrusor overactivity and seven with other miscellaneous
diagnoses. Patients presenting with this symptom complex should be evaluated so
that treatment can be tailored appropriately.
PMID- 9650044
TI - Complications of vascular access in hemodialysis (HD)--aged vs adult patients.
AB - Reports on the success of permanent vascular access in elderly HD patients vary
considerably. We reviewed the records of 149 patients [62F and 87M] aged 20-89
years old (median 59) who were on hemodialysis for 6-242 (49 median) months, and
had undergone 202 vascular access procedures (177 Cimmino-Brescia fistulae and 25
PTFE grafts). Patients were divided into two groups according to the age they
started HD. Group A: 48 patients, over 60 years old (range 60-83; median 70) on
HD for 43.5, (6-140) months. Group B: 101 patients, under 60 years old, range (15
59) median 46, on HD for 54 (6-242) months. There were no differences between the
two groups in terms of gender, primary renal disease, (except polycystic kidney
disease), Hct and EPO administration. The initial choice of vascular access, the
complications and the technique survival were examined in both groups. Cimmino
Brescia fistulae were used as the first choice of vascular access in all patients
except one in group B. PTFE-grafts were the second or third choice in 7/48 (group
A) and 15/101 (group B) (p: NS). The only reason for technique failure was
vascular thrombosis in both groups (11/48 group A and 31/101 group B p: NS).
Other complications were: aneurysms (10/48 and 14/101, p: NS), infections (0/48
and 2/101 p: NS) and edema (0/48 and 6/101, p: NS). Five-year technique survival
of the first AV fistula in the two groups was 35% and 45% respectively (log-rank
test, p: NS). These findings suggest that: a) A.V. fistula is the first choice of
vascular access in aged HD patients; b) There is no difference in vascular access
complications across age groups; c) Survival of the first A.V. fistula is
independent of age.
PMID- 9650046
TI - Nephrologic complications of drug therapy in the elderly.
PMID- 9650047
TI - Acute renal failure in an elderly patient.
PMID- 9650048
TI - Refractory severe nocturia: its treatment with intranasal desmopressin.
PMID- 9650049
TI - Novel vaccines against Theileria parva: prospects for sustainability.
AB - A first-generation subunit vaccine for East Coast fever based on the Theileria
parva p67 sporozoite surface antigen is entering preliminary field trials.
Intensive efforts are also focused on the identification of a schizont-specific
component for incorporation in a second-generation multi-component product. It is
clear that many questions remain unanswered regarding the likely performance of
these vaccines under field conditions. In particular, their effect on the endemic
status of the parasite in targeted areas will be crucial to their sustainability.
Ideally, challenge should be maintained so that immunity is boosted in the
absence of repeat vaccination. In the event that efficacy of the p67 vaccine in
the field reflects that observed in extensive laboratory trials, it is possible
that some reduction in the heterogeneity of the indigenous parasite population
will occur, and this may be accompanied by selection for more highly infective
strains. In contrast, available information suggests that schizont-specific
components of a second-generation subunit vaccine are unlikely to affect the
endemic status of parasite populations. However, endemic stability will
inevitably decline as management systems become more intensive and necessitate
frequent vaccination to maintain protective cover.
PMID- 9650050
TI - Binding of [3H]m-aminolevamisole to receptors in levamisole-susceptible and
resistant Haemonchus contortus.
AB - M-aminolevamisole, a potent analogue of the commercial anthelmintic levamisole,
was used to investigate ligand-binding properties of homogenates of larval and
parasitic stages of the nematode parasite of sheep, Haemonchus contortus.
Kinetics of the binding of [3H]m-aminolevamisole to homogenates was measured in a
drug-susceptible isolate and compared with a levamisole-resistant isolate.
Equilibrium binding studies and kinetic studies revealed a high affinity binding
component with a KD of 3 nM. A low affinity component (KD = 2.4 microM) was also
apparent in equilibrium studies. High affinity [3H]m-aminolevamisole binding was
displaced in a concentration-dependent manner by levamisole analogues and
cholinergic agonists. Compared with the susceptible isolate, binding in a
levamisole-resistant isolate of the parasite, was quantitatively similar over a
range of developmental stages and binding conditions. However, under the
conditions of binding there was a reduced affinity (larger KD) and more binding
sites (larger Bmax) at the low affinity site in the resistant compared with the
susceptible isolate. It was concluded that the ligand was binding to
acetylcholine receptor populations of the nematode and that resistance may be
associated with alterations in the low affinity site of this receptor.
PMID- 9650051
TI - Determinants of transmission success of individual clones from mixed-clone
infections of the rodent malaria parasite, Plasmodium chabaudi.
AB - Interactions between malaria parasite clones within mixed infections can have a
profound effect on transmission and therefore the epidemiology of the disease.
However, factors which determine the relative transmission success of individual
clones from mixed infections are unknown. We have used two clones of the rodent
malaria Plasmodium chabaudi to investigate changes in the clonal composition of
asexual parasites over the course of mixed-clone infections in mice and how these
relate to the clonal composition of transmission (oocyst) populations in
mosquitoes. Clonal composition was determined using monoclonal antibody analyses
for the asexual blood stage populations and PCR analysis of single oocysts for
the transmission populations in mosquitoes. The relative frequency of the two
clones changed dramatically during the course of the infection in mice, depending
on their ratio in the inoculum. The clonal composition of parasites within
mosquitoes most closely resembled that in the asexual infection at the time of
transmission rather than that at any point earlier in the infection. These
results provide no evidence that clones increase rates of gametocytogenesis in
response to competitive suppression. Most likely, transmission success follows
from asexual success in the later parts of the infection. The clone which
dominated the earlier part of the infection, when most parasites are produced,
did not necessarily dominate the transmission from the infection. The two clones
differed in competitive ability and the data suggest that interactions with the
host immune system may be a major factor in determining transmission success from
mixed-clone infections.
PMID- 9650052
TI - Parasite extinction and colonisation and the evolution of parasite communities: a
simulation study.
AB - We determined what evolutionary processes influence the likelihood of detecting
an effect of host ecological characteristics on the richness of parasite
communities in comparative analyses among related host species. We used a
mathematical model to generate phylogenies of hosts in which parasite communities
varied over evolutionary time as parasite species were either gained or lost
during host speciation events. Gain or loss of parasites were stochastic and
could either be strongly, moderately, weakly, or not, affected by host ecological
characteristics. The model was evaluated over this range of effects of host
ecology, and for various mean probabilities of parasite gain and loss and various
rates of change in host ecological characteristics at speciation events. Our
results suggest that phylogenetic effects (the passing of parasite species from
mother to daughter host species) are likely to obscure ecological effects (the
effect of host body size, diet, habitat, lifespan, etc.) except when the effects
of host ecology are strong, and the probabilities of gain or loss of parasites
are high, or host ecological characteristics change markedly at speciation
events. This outcome was not influenced by the shape of the phylogenetic tree
used in the simulations. Sensitivity analysis of our model also shows this result
to be robust to a wide range of assumptions and parameter values. Thus, because
the composition of parasite communities tends to reflect their ancestry, the
effect of host ecology will often be very difficult to detect.
PMID- 9650053
TI - Attempts to generate immunity against Trichostrongylus colubriformis and
Haemonchus contortus in young lambs by vaccination with viable parasites.
AB - The ability of young Merino lambs to achieve protective immunity following
vaccination via viable nematode infections was assessed. Lambs were infected from
1 month of age by repeated continuous low dose (trickle) administration of
Trichostrongylus colubriformis or Haemonchus contortus infective larvae (L3), or
by truncated infections with high doses of viable T. colubriformis L3. After 7
weeks all groups were drenched with anthelmintic and at 3 months of age they were
re-infected with the homologous species. Protection was assessed by faecal egg
counts at 3, 4, 5, 6 and 7 weeks after challenge, and worm count at 7 weeks after
challenge. Young lambs were partially protected by 3 months of age against
Trichostrongylus by trickle infection. This protection correlated with local mast
cell and T-cell priming, increased numbers of local antigen-presenting cells and
T-cells and increased worm-specific antibody titres in the intestine. However,
there was no evidence that young lambs were capable of immunologically
recognising H. contortus antigens following trickle infection, nor did trickle
infection significantly protect young lambs against Haemonchus challenge.
PMID- 9650054
TI - The effects of parasites on a wild population of the Mountain Brushtail Possum
(Trichosurus caninus) in south-eastern Australia.
AB - The effects of a reduction of parasite burdens were determined in adult female
Mountain Brushtail Possums, Trichosurus caninus, on the birth, mortality and
growth rates of pouch-dependent young, as well as the haematological and serum
biochemical values of the mothers. The efficacy of the anthelmintic drug
ivermectin for reducing parasite burdens in this host was assessed using faecal
and necropsy examinations of a small number of animals. Ivermectin began to
reduce parasite burdens by 48 h after treatment. In the second stage of the
experiment, animals were treated or sham injected (control individuals) with
ivermectin and praziquantel at 8-10-week intervals throughout the breeding season
to the time of emergence of young from the pouch. Treatment with ivermectin and
praziquantel had no significant effect on the proportion of females giving birth,
or on the survival of young to emergence. An effect of treatment was recorded for
absolute eosinophil counts in adult females, which, in spring; were higher among
control animals than those that were treated.
PMID- 9650055
TI - A Taenia solium oncosphere protein homologous to host-protective Taenia ovis and
Taenia saginata 18 kDa antigens.
AB - A Taenia solium cDNA (TSOL-18) encoding a protein with close homology to host
protective oncosphere antigens from Taenia ovis (To18) and Taenia saginata (TSA
18) is described here. TSOL-18 was cloned from mRNA obtained from hatched and
activated oncospheres of T. solium. The high level of predicted amino acid
sequence homology among TSOL-18 and other host protective taeniid antigens
suggests that the protein expressed by TSOL-18 may be capable of being used as a
vaccine against T. solium infection in the parasite's intermediate hosts.
PMID- 9650056
TI - Quantitative and qualitative changes in intestinal goblet cells during primary
infection of Trichostrongylus colubriformis high and low responder guinea pigs.
AB - Small intestine goblet cell numbers and the composition of their mucus were
compared in guinea pigs with genetically determined differences in responsiveness
to Trichostrongylus colubriformis infection. Prior to infection, no differences
between high responder and low responder animals were detected. However,
following primary infection with T. colubriformis, pronounced goblet cell
hyperplasia developed and the proportion of sulphomucin in these cells increased.
Both changes developed significantly earlier in high responder animals.
PMID- 9650057
TI - Molecular phylogeny of the families Campulidae and Nasitrematidae (Trematoda)
based on mtDNA sequence comparison.
AB - Historically, the systematic arrangement of the genera within the family
Campulidae, and its relationship with its allied family Nasitrematidae have been
rather confused, particularly because only adult morphology has been available to
classical taxonomic analysis. In this paper we provide a partial phylogeny of the
genera of these families based on mtDNA from five campulid species: Campula
oblonga, Zalophotrema atlanticum, Hadwenius tursionis, Oschmarinella rochebruni
and Orthosplanchnus fraterculus; and one nasitrematid, Nasitrema globicephalae.
Fasciola hepatica and Dicrocoelium dendriticum were used as outgroups. Maximum
parsimony and neighbour-joining methods were applied. Both methods produced
similar trees where H. tursionis appeared as the basal campulid, with a
sequential divergence of Z. atlanticum, N. globicephalae, C. oblonga, O.
rochebruni and O. fraterculus. Results suggest that Nasitrematidae as defined
should loose its familial status and the current subfamilial division of the
family Campulidae is at least partly artificial and should not be maintained.
PMID- 9650058
TI - Triploid form of Fasciola in Japan: genetic relationships between Fasciola
hepatica and Fasciola gigantica determined by ITS-2 sequence of nuclear rDNA.
AB - The ITS-2 sequences from seven worms of the Japanese triploid form of Fasciola,
two of Fasciola hepatica from Uruguay and four of Fasciola gigantica from Zambia
and Indonesia were determined. The ITS-2 sequences of the Japanese triploid worms
were divided into two distinct types, one of which was almost identical to that
of F. hepatica and the other to F. gigantica from Indonesia.
PMID- 9650059
TI - Evidence of multiple mechanisms of avermectin resistance in haemonchus contortus-
comparison of selection protocols.
AB - Three isolates of Haemonchus contortus selected for avermectin resistance in
sheep were compared in three in vitro pharmacological tests previously shown to
discriminate between field isolates of H. contortus resistant and susceptible to
the avermectins. Two isolates, F7-A and IVC, were selected for avermectin
resistance in the laboratory from a reference susceptible isolate using
suboptimal doses of ivermectin (LD95) for 7 and 16 generations, respectively. In
these isolates avermectin resistance was not associated with a decreased
sensitivity to avermectin inhibition of larval development or L3 motility but was
associated with an increased sensitivity to paraherquamide. The third isolate,
Warren, was derived from an overwhelmingly avermectin-susceptible, mixed species
field isolate in a single generation by propagating the small number of survivors
of a 0.2 mg/kg ivermectin treatment (i.e. 10 x LD95). This isolate, like
previously characterised avermectin-resistant H. contortus isolates derived from
the field in South Africa and Australia, showed a markedly reduced sensitivity to
avermectin inhibition of larval development and L3 motility, as well as an
increased sensitivity to paraherquamide. These results suggest that avermectin
resistance can manifest itself in different ways and that the two selection
protocols used to generate the F7-A, IVC and Warren isolates have resulted in the
selection of different resistance phenotypes.
PMID- 9650060
TI - Effect of plant species on the larvae of gastrointestinal nematodes which
parasitise sheep.
AB - Faeces containing Trichostrongylus colubriformis and/or Ostertagia circumcincta
eggs were used to provide four contaminations in each of 2 years on plots of
browntop, Yorkshire fog, ryegrass, tall fescue, lucerne, chicory, cocksfoot,
white clover, and prairie grass and in the second year a mixed sward of
ryegrass/white clover. Third stage larvae were recovered from faeces and from
four strata of herbage, 0-2.5, 2.5-5, 5-7.5 and > 7.5 cm above the soil surface
at 2, 4, 6, 8, 11, and 14 weeks after faeces were deposited on the swards.
Herbage species had a significant (P < 0.0001) effect on the number of larvae
recovered. Greatest numbers of larvae, as indicated by ranking analysis, were
recovered from Yorkshire fog, ryegrass, and cocksfoot and lowest numbers from
white clover and lucerne. The difference between herbages in numbers of larvae
recovered was due to the "development success", the ability of larvae to develop
to the infective stage and migrate on to herbage, rather than "survival", the
rate of population decline once on the herbage. Faecal degradation was most rapid
from white clover and browntop, intermediate from tall fescue, lucerne, prairie
grass, cocksfoot, and ryegrass, and slowest from Yorkshire fog swards. The
numbers of larvae recovered from herbages were related (r2 = 0.59, P < 0.05) with
the faecal mass remaining. A greater proportion of the total larvae recovered
from the herbage was recovered from the bottom stratum of Yorkshire fog and
prairie grass than from white clover, with the other herbages intermediate,
indicating that larvae had greater difficulty migrating up Yorkshire fog and
prairie grass than the other herbage species. In most herbage species, despite
more larvae being recovered from the lowest stratum, larval density (L3/kg
herbage DM) was highest in the top stratum. This study has demonstrated that
herbage species can have a significant impact on the population dynamics and
vertical migration of T. colubriformis and O. circumcincta larvae.
PMID- 9650061
TI - The application of chaetotaxy in the discrimination of Gyrodactylus salaris
Malmberg, 1957 (Gyrodactylidae: Monogenea) from species of the genus parasitising
British salmonids.
AB - The chaetotaxy of argentophilic structures on three species of the monogenean
genus Gyrodactylus was investigated in an attempt to distinguish species of this
genus. Maps were prepared for Gyrodactylus salaris from Scandinavia and compared
with two native species of Gyrodactylus parasitising salmonids in Britain, namely
Gyrodactylus derjavini and Gyrodactylus truttae. The maps were subsequently
refined and analysed for zones of homology and differentiation. The results
demonstrate that G. salaris can be readily distinguished by this technique, which
is, therefore, of great potential value in the identification of this notifiable
pathogen. The key aggregations of sensilla discriminating G. salaris are,
ventrally, the antero-ventral set, the medio-lateral set and the postero-lateral
set, and, dorsally, the postero-dorsal set.
PMID- 9650062
TI - Association of host cell intermediate filaments with Toxoplasma gondii cysts in
murine astrocytes in vitro.
AB - Toxoplasma gondii is an intracellular parasite that is a common opportunistic
infection of AIDS patients where it causes a severe and often fatal encephalitis.
Toxoplasmic encephalitis in AIDS patients results from a reactivation of the cyst
stage of Toxoplasma gondii in the brain. A previous study found an association of
host cell intermediate filaments with parasitophorous vacuoles and some studies
have suggested the host cell cytoskeletal elements are incorporated into the cyst
wall. In this study, the interaction of glial filaments with Toxoplasma gondii
cysts was studied in cysts derived in vitro in mouse astrocytes and in cysts
isolated from mouse brains. Glial filaments, detected by immunostaining of the
glial fibrillary acidic protein, were found to accumulate around the perimeter of
the cysts as they developed in mouse astrocytes. Transmission electron microscopy
revealed a layer of glial filaments was wrapped around the cytoplasmic side of
the cyst. The glial filaments were present in close apposition to the cyst wall
and arranged around the cysts in a concentric layer, measuring 5-10 microns in
thickness. The layer of glial filaments excluded host cell mitochondria and
endoplasmic reticulum from the cytoplasmic surface of the cyst. Colocalisation of
glial fibrillary acidic protein and the cyst wall via confocal and immunoelectron
microscopy, confirmed that there was no glial fibrillary acidic protein present
within the cyst wall. The cyst wall of cysts isolated from mouse brains were also
found to be negative for glial fibrillary acidic protein. In conclusion, we found
no evidence of structural integration of the host cell intermediate filaments in
the cyst wall, but glial filaments were found to encase the cysts in the host
cell during cyst development in host cells in vitro. The glial filaments wrapping
of cysts may play a role in bradyzoite differentiation and/or cyst stabilisation
in the host cell cytoplasm.
PMID- 9650063
TI - Immunocytochemical detection of vasoactive intestinal peptide-like and peptide
histidine isoleucine-like peptides in the nervous system and the excretory system
of adult Nippostrongylus brasiliensis.
AB - Vasoactive intestinal peptide-like and peptide histidine isoleucine-like
immunoreactivities were detected in the excretory duct of adult male and female
Nippostrongylus brasiliensis, thus indicating the source of these two
physiologically active peptides previously isolated from the excretory/secretory
products of adult N. brasiliensis. In the nervous system immunoreactivity to both
these peptides was confined to females and was found in the neurons of the
ovijector associated ganglion. This is consistent with co-synthesis of vasoactive
intestinal peptide-like and peptide histidine isoleucine-like peptides which has
also been shown to occur in all mammalian vasoactive intestinal peptid-ergic
neurons studied to date. However, in addition to this, and in common to some
previous studies on helminth vasoactive intestinal peptide and peptide histidine
isoleucine immunoreactivities, co-synthesis of the peptides was not indicated in
a pair of branched neurons which projected posteriorly and peripherally from the
ganglion associated with the ovijector of females and which terminated in two
pairs of ganglia also exhibiting vasoactive intestinal peptide-like
immunoreactivity only. The position of these ganglia indicated that they
innervate muscles close to the body wall and may be responsible for the muscular
contractions required for expulsion of eggs from female Nippostrongylus
brasiliensis. This is also the first study to successfully detect these peptides
in the excretory system of gastrointestinal nematodes.
PMID- 9650064
TI - Comparative sequence analysis of the intergenic spacer region of cyathostome
species.
AB - The ribosomal DNA intergenic spacer was amplified by the polymerase chain
reaction from 16 cyathostome species using primers derived from conserved regions
within the flanking 18S and 26S rRNA genes. This generated a 1.5-2.5 kb fragment
which was sequenced from five species. The areas covering the 26S and 18S rRNA
genes were more than 99% similar among the five species. Furthermore, in all
species there existed a highly conserved region of approximately 380 bp at the 3'
end of the intergenic spacer. Subsequently, two cyathostome-specific primers were
designed to amplify a smaller, more variable region of the intergenic spacer.
Eleven further species were amplified using these primers and analysis showed
that sequence similarities varied from 40 to 97% between species. The sequence
information obtained in this study is being used to develop a PCR-based assay for
the differentiation of preparasitic stages of cyathostomes.
PMID- 9650065
TI - Grandparental impact in young adults' relationships with their closest
grandparents: the role of relationship strength and emotional closeness.
AB - This study explored the role that relationship strength, generally, and emotional
closeness, more specifically, may play in delimiting the bounds of grandparental
influence in young adults' lives. One-hundred and seventy-one college-aged young
adults completed a questionnaire evaluating their relationship with the living
grandparent to whom they felt most emotionally close or, if they felt close to
none of their living grandparents, the grandparent with whom they had the most
contact. Participants' perceptions of the strength of this relationship were
significantly and positively related to their responses on measures of the extent
to which their closest grandparent influenced various aspects of their lives
(e.g., their beliefs and values, how much their lives would be missing had they
never known the grandparent). In addition, participants whose grandparent
grandchild relationships were emotionally close endorsed a broader range of
alternatives on checklist measures of perceived relationship impact than did
those whose relationships were more emotionally distant.
PMID- 9650066
TI - (Re)constructing relationships with grandparents: a turning point analysis of
granddaughters' relational development with maternal grandmothers.
AB - This study explores how granddaughters account for the development of their
relationships with their maternal grandmothers. The retrospective interviewing
technique was used to elicit turning points in their relational histories.
Analysis of the turning point content revealed several different types of turning
points that reflected both normative and idiosyncratic events. Increases in
relational closeness resulted from decreases in geographic separation, engaging
in shared activities, deaths or serious illnesses in the family, and family
disruptions. Decreases in closeness were associated with negative experiences
with the grandmother, increases in geographic separation, and the transition to
college. Granddaughters reported that turning points related to death or serious
illness and participation in shared activities were the most significant ones in
their relationships with maternal grandmothers.
PMID- 9650067
TI - Coping with the stress of immigration among new immigrants to Israel from
Commonwealth of Independent States (CIS) who were exposed to Chernobyl: the
effect of age.
AB - This study examined the differential effect of age on coping and psychological
measures among immigrants from Commonwealth of Independent States (CIS) to
Israel. Some of these immigrants originated in the Republics adjacent to the
Chernobyl Power Plant, site of the 1986 accident. The sample consisted of 708
immigrants who were interviewed between the years 1993-1995 with an average age
of 47.5 (sd 11.8). This sample was reinterviewed approximately a year and three
months later (n = 520). The sample included two exposure groups--high exposed and
low exposed based on the estimated levels of ground cesium contamination from the
IAEA maps and a comparison group matched by age, gender, and year of immigration.
Those over the age of sixty-five were disadvantaged, compared to those aged fifty
to sixty-four, and younger, when it came to the tasks of immigrant absorption;
learning the language, working and acquiring an income, and establishing
alternative social networks which could offer support in times of illness. The
psychological variables showed that over time, somatization, depression, and post
traumatic stress disorder (PTSD) symptoms related to Chernobyl improved, however
at a much slower pace for older immigrants (aged 55 and over) compared to younger
ones.
PMID- 9650068
TI - Measurement of aging anxiety in an elderly Australian population.
AB - The purpose of this investigation was to modify an existing aging anxiety scale
to produce an instrument specifically designed to assess aging anxiety in an
elderly population. Existing instruments fail to consistently orientate aging
associated threats into the future, and this poses a significant problem for the
measurement of aging anxiety in the elderly population. It is proposed that this
factor has confounded reports of the relationship between aging anxiety and
advancing age. An existing valid and reliable instrument, the Anxiety about Aging
Scale was modified for use with elderly respondents and tested on 123 independent
community dwelling elderly individuals. The results indicated the modified scale
provides a valid assessment of aging anxiety in the elderly.
PMID- 9650069
TI - The association between mortality, morbidity and age in New Zealand's oldest old.
AB - People aged eighty-five years and over (the oldest old) will form an increasing
proportion of the population of New Zealand and many other countries. Because of
their smaller numbers and relative inaccessibility, their health status has
sometimes been extrapolated from populations of people aged sixty-five to eighty
four years. For people aged sixty-five to eighty-four years an exponential
relationship is seen between age and morbidity and mortality. We explore if this
exponential relationship extends to people aged ninety years and over. We
analyzed data from the New Zealand 1991 Census and 1992 hospital discharge
records and, for people aged sixty to eighty-nine years, confirmed an exponential
relationship between age and mortality, inactivity, hospital utilization, and
occupation of residential institutions. This exponential trend did not continue
for people aged ninety years and over for whom mortality rates and indicators of
morbidity were considerably lower than expected, and conclude that the actual
health status of people aged ninety years and over is better than the status
extrapolated from that of people aged sixty to eighty-nine years.
PMID- 9650070
TI - Genealogy of the alpha-crystallin--small heat-shock protein superfamily.
AB - Sequences of 40 very diverse representatives of the alpha-crystallin-small heat
shock protein (alpha-Hsp) superfamily are compared. Their characteristic C
terminal 'alpha-crystallin domain' of 80-100 residues contains short consensus
sequences that are highly conserved from prokaryotes to eukaryotes. There are, in
addition, some positions that clearly distinguish animal from non-animal alpha
Hsps. The alpha-crystallin domain is predicted to consist of two hydrophobic beta
sheet motifs, separated by a hydrophilic region which is variable in length.
Combination of a conserved alpha-crystallin domain with a variable N-terminal
domain and C-terminal extension probably modulates the properties of the various
alpha-Hsps as stress-protective and structural oligomeric proteins. Phylogeny
reconstruction indicates that multiple alpha-Hsps were already present in the
last common ancestor of pro- and eukaryotes. It is suggested that during
eukaryote evolution, animal and non-animal alpha-Hsps originated from different
ancestral gene copies. Repeated gene duplications gave rise to the multiple alpha
Hsps present in most organisms.
PMID- 9650071
TI - The effect of the intersubunit disulfide bond on the structural and functional
properties of the small heat shock protein Hsp25.
AB - The murine small heat shock protein Hsp25 carries a single cysteine residue in
position 141 of its amino acid sequence. Interestingly, Hsp25 can exist within
the cell as covalently bound dimer which is linked by an intermolecular disulfide
bond between two monomers. Oxidative stress caused by treatment of the cells with
diamide, arsenite, or hydrogen peroxide leads to an increase in Hsp25
dimerisation which can be blocked by simultaneous treatment with reducing agents.
Recombinant Hsp25 was prepared in an oxidized dimeric (oxHsp25) and reduced
monomeric (redHsp25) from. The two species were compared with regard to secondary
structure, stability, oligomerization properties and their chaperone activity. It
is demonstrated by CD measurements in the far UV region that there are no
significant differences in the secondary structure and temperature- or pH
stability of oxHsp25 and redHsp25. However, according to CD measurements in the
near UV region an increase in the asymmetry of the microenvironment of aromatic
residues in oxHsp25 is observed. Furthermore, an increase in stability of the
hydrophobic environment of the tryptophan residues mainly located in the N
terminal domain of the protein against urea denaturation is detected in oxHsp25.
Both reduced and oxidized Hsp25 from oligomeric complexes of similar size and
stability against detergents and both species prevent thermal aggregation of
citrate synthase and assist significantly in oxaloacetic acid-induced refolding
of the enzyme. Hence, the overall secondary structure, the degree of
oligomerization and the chaperone activity of Hsp25 seem independent of the
formation of the intermolecular disulfide bond and only the stability of the
hydrophobic N-terminal part of the molecule is influenced by formation of this
bound. The obtained data do not exclude the possible involvement of dimerization
of this protein in other cellular functions, e.g. in intracellular sulfhydryl
buffering or in the protection of actin filaments from fragmentation upon
oxidative stress.
PMID- 9650072
TI - Refinement of 3D structure of bovine lens alpha A-crystallin.
AB - In absence of 3D structures for alpha-crystallin subunits, alpha A and alpha B,
we utilized a number of experimental and molecular modeling techniques to
generate working 3D models of these polypeptides (Farnsworth et al., 1994. In
Molecular Modeling: From Virtual Tools to Real Problems (Eds. Kumosinski, T.F.
and Liebman, M.N.) ACS Symposium Series 576, Ch. 9:123-134, 1994, ACS Books,
Washington DC). The refinement of the initial bovine alpha A model was achieved
using a more accurate estimation of secondary structure by new/updated methods
for analyzing the far UV-CD spectra and by neural network secondary structure
predictions in combination with database searches. The spectroscopic study
reveals that alpha-crystallin is not an all beta-sheet protein but contains
approximately 17% alpha-helices, approximately 33% beta-structures and
approximately 50% turns and coils. The refinement of the alpha A structure
results in an elongate, asymmetric amphipathic molecule. The hydrophobic N
terminal domain imparts the driving force for subunit aggregation while the more
flexible, polar C-terminal domain imparts aggregate solubility. In our quaternary
structure of the aggregate, the monomer is the minimal cooperative subunit. In
bovine alpha A, the highly negatively charged C-terminal domain has three small
positive areas which may participate in dimer or tetramer formation of
independently expressed C-terminal domains. The electrostatic potential of
positive areas is modulated and become more negative with phosphorylation and ATP
binding. The refined bovine alpha A model was used to construct alpha A models
for the human, chick and dogfish shark. A high degree of conservation of the
three dimensional structure and the electrostatic potential was observed. Our
proposed open micellar quaternary structure correlates well with experimental
data accumulated over the past several decades. The structure is also predictive
of the more recent data.
PMID- 9650073
TI - Mutations and modifications support a 'pitted-flexiball' model for alpha
crystallin.
AB - alpha-Crystallin is renown for resisting crystallization and electron microscopic
image analysis. The spatial conformation thus remaining elusive, the authors
explored the structure and chaperone functioning by analyzing the effects of site
directed mutagenesis, the properties of naturally occurring aberrant forms of
alpha-crystallin and the influence of chemical modifications. The authors
observed that the globular multimeric structure, as well as the chaperoning
capacity are remarkably tolerant towards changes and modifications in the primary
structure. The essential features of the quaternary structure--globular shape,
flexibility, highly polar exterior and accessible hydrophobic surface pockets-
support a 'pitted-flexiball' model, which combines tetrameric subunit building
blocks in an open micelle-like arrangement.
PMID- 9650074
TI - NMR spectroscopy of alpha-crystallin. Insights into the structure, interactions
and chaperone action of small heat-shock proteins.
AB - The subunit molecular mass of alpha-crystallin, like many small heat-shock
proteins (sHsps), is around 20 kDa although the protein exists as a large
aggregate of average mass around 800 kDa. Despite this large size, a well
resolved 1H NMR spectrum is observed for alpha-crystallin which arises from
short, polar, highly-flexible and solvent-exposed C-terminal extensions in each
of the subunits, alpha A- and alpha B-crystallin. These extensions are not
involved in interactions with other proteins (e.g. beta- and gamma-crystallins)
under non-chaperone conditions. As determined by NMR studies on mutants of alpha
A-crystallin with alterations in its C-terminal extension, the extensions have an
important role in acting as solubilising agents for the relatively-hydrophobic
alpha-crystallin molecule and the high-molecular-weight (HMW) complex that forms
during the chaperone action. The related sHsp, Hsp25, also exhibits a flexible C
terminal extension. Under chaperone conditions, and in the HMW complex isolated
from old lenses, the C-terminal extension of the alpha A-crystallin subunit
maintains its flexibility whereas the alpha B-crystallin subunit loses, at least
partially, its flexibility, implying that it is involved in interaction with the
'substrate' protein. The conformation of 'substrate' proteins when they interact
with alpha-crystallin has been probed by 1H NMR spectroscopy and it is concluded
that alpha-crystallin interacts with 'substrate' proteins that are in a
disordered molten globule state, but only when this state is on its way to large
scale aggregation and precipitation. By monitoring the 1H and 31P NMR spectra of
alpha-crystallin in the presence of increasing concentrations of urea, it is
proposed that alpha-crystallin adopts a two-domain structure with the larger C
terminal domain unfolding first in the presence of denaturant. All these data
have been combined into a model for the quaternary structure of alpha-crystallin.
The model has two layers each of approximately 40 subunits arranged in an annulus
or toroid. A large central cavity is present whose entrance is ringed by the
flexible C-terminal extensions. A large hydrophobic region in the aggregate is
exposed to solution and is available for interaction with 'substrate' proteins
during the chaperone action.
PMID- 9650075
TI - alpha-Crystallin quaternary structure and interactive properties control eye lens
transparency.
AB - The eye lens is the foremost biological system where function is directly under
control of the physico-chemical properties of the cytoplasmic macromolecular
solution. Indeed, lens transparency and opacity, lens refractive index gradient
and viscosity, are the result of the structural and interactive properties of the
crystallins, of their stability, of the fine tuning of their interaction
potentials and associations at different levels of organization. Among the
different crystallin classes, alpha-crystallins have represented a major
challenge for a long time. The alpha-crystallin secondary, tertiary and
quaternary structures are still unknown. On the functional side, however, it is
established that alpha-crystallin quaternary structure and repulsive interactions
determine lens transparency, whereas the alpha-crystallin chaperone effect most
probably plays a role in the aging process. In the present paper, we recall the
physico-chemical properties and the quaternary structure features of alpha
crystallins that were demonstrated to control light scattering and transparency.
The interest of a crystallin mixture for lens function is discussed. Then, a
formal approach is proposed to design models for the alpha-crystallin quaternary
structure, including the question of whether alpha-crystallins assemble with
symmetry. An hypothesis relevant to the fold of the alpha-crystallin C-terminal
domain is presented in another paper in this issue.
PMID- 9650076
TI - alpha-Crystallin C-terminal domain: on the track of an Ig fold.
AB - New results obtained from a two-dimensional sequence analysis of the small heat
shock protein (shsp) family are described. It is confirmed that the conserved C
terminal alpha-crystallin domain is essentially made of beta-strands, most
probably two groups of beta-strands separated by a large loop. A direct
correspondence between the putative beta-strands that have been identified in
shsps and the seven beta-strands of a classical immunoglobulin-like fold is
proposed. The hypothesis that the shsp family could belong to the immunoglobulin
superfamily (IgSF) is consistent with the ubiquitous distribution and the
multifunctional properties of the crystallins that are now emerging.
PMID- 9650077
TI - Quaternary structure of bovine alpha-crystallin: influence of temperature.
AB - The tertiary and quaternary structure of alpha-crystallin is still a matter of
controversy. We have characterized the native alpha-crystallin quaternary
structure by isolating it at the in vivo temperature and solvent conditions. It
can be represented by a distribution of expanded particles with a weight average
molar mass of 550,000 g/mol. On decreasing (to 4 degrees C) or increasing (up to
50 degrees C) the temperature, the size distribution increases to larger
particles. Only at lower temperatures (4 degrees C), a stable population of
particles is obtained with weight average molar mass of 700,000 g/mol. In all
conditions, alpha-crystallin behaves as a very expanded particle with a maximum
hydrodynamic volume of 3.15 ml/g. The transitions in quaternary structure are
rather slow: it takes several hours to evolve from a population of aggregates,
characteristic for given solvent conditions, to another distribution in size and
quaternary structure on changing the environment. The quaternary structure of
alpha-crystallin is an uncharacteristic parameter of the particle: a broad
distribution of values can be obtained on changing the environment. Any realistic
model should include this property. Our studies favor an open loose structure,
where peptides can be added or removed without drastic changes of secondary and
tertiary structure of the peptides.
PMID- 9650078
TI - Hydrophobicity and flexibility of alpha A- and alpha B-crystallin are different.
AB - Since the discovery that the lens protein alpha-crystallin is also found in non
lenticular tissues and can function as a chaperone, relatively little attention
has been paid to differences in properties between alpha A- and alpha B
crystallin, which form mixed aggregates in the lens but have so far never been
found together in other tissues. In this study hydrophobicity and flexibility,
properties that are thought to be relevant for chaperone function, are compared
for alpha A- and alpha B-crystallin. Hydrophobicity was monitored from sodium
dodecylsulphate polyacrylamide gel electrophoresis in the absence and presence of
(methyl-substituted) ureas. Flexibilities were calculated from primary
structures. Based on literature data also some other properties are compared. The
results indicate significant difference in hydrophobicity profile, flexibility of
the terminal parts and stability of alpha A- and alpha B-crystallin.
PMID- 9650079
TI - Thermodynamic stability of bovine alpha-crystallin in its interactions with other
bovine crystallins.
AB - Light scattering measurements were performed on dilute solutions of alpha
crystallin mixed with different combinations of beta H, beta L and gamma
fractions of bovine lens crystallins. Light scattering intensities were obtained
as a function of scattering angle, concentration and temperature. The temperature
dependence of the second virial coefficients was used to obtain partial molar
enthalpy and end entropy of solutions. The difference between the thermodynamic
parameters of the crystallin mixtures and those of the weighted averages of the
individual components yielded the excess enthalpy and entropy functions of the
solutions. Both the excess enthalpy and entropy functions indicated that
thermodynamic stability of alpha-crystallin is progressively enhanced by its
interactions with gamma [symbol: see text] (beta H + gamma) [symbol: see text]
(beta H + beta L + gamma) crystallins. The last two combinations showed negative
values both for excess enthalpy as well for excess entropy of solutions. Other
combinations demonstrated increasing positive values. This implies that the
combination of all four crystallins in the vertebrate lens enables the best
solvation property as well as the best packing as opposed to any other single or
combinatorial arrangements of crystallins. Similar conclusions have been obtained
in the past from water and other vapor sorption studies.
PMID- 9650080
TI - alpha-Crystallin polymers and polymerization: the view from down under.
AB - Several models have been proposed for the quaternary structure of alpha
crystallin. Some suggest the subunits are arranged in concentric shells. Others
propose that the subunits are in a micelle-like arrangement. However, none is
able to satisfactorily account for all observations on the protein and the
quaternary structure of alpha-crystallin remains to be established. In this
review, factors contributing to the assembly and polymerization are examined in
order to evaluate the different models. Consideration of the variations in
particle size and molecular weight under different conditions leads to the
conclusion that alpha-crystallin cannot be a micelle or a layered structure.
Instead, it is suggested that the protein may be assembled from a 'monomeric'
unit comprising eight subunits arranged in two tetramers with cyclic symmetry.
The octameric unit is proposed to be disc-like particle with a diameter of 9.5 nm
and a height of 3 nm. The larger particles, chains and sheet-like structures
commonly observed are assembled from the octamers. Structural predictions
indicate that the polypeptide may be folded into three independent domains which
have different roles in the structural organization and functions of the protein.
It is suggested that the tetramers are stabilized through interactions involving
the second domain (residues 64-104) while assembly into the octamers and higher
polymers requires hydrophobic interactions involving the N-terminal domain.
Deletion of parts of this domain by site directed mutagenesis revealed that
residues 46-63 play a critical role in the assembly. Current research aims to
identify the specific amino acids involved.
PMID- 9650081
TI - Mutation of alpha B-crystallin: effects on chaperone-like activity.
AB - A recent paper by Plater et al. [20], showed that the mutation of a single
phenylalanine residue F27R in mouse alpha B completely abolished the chaperone
like property of alpha-crystallin when assayed with insulin at 25 degrees C or
with gamma-crystallin at 66 degrees C. We have produced the same mutation as well
as some additional mutations in human alpha B-crystallin. Our data suggest that
the F27R mutation effected the thermal stability of alpha B-crystallin making it
unstable at temperatures > or = 60 degrees C. In agreement with the published
work, at these temperatures the F27R human recombinant alpha B-crystallin does
not protect the target protein from aggregation. When assayed with insulin or
alpha-lactalbumin at 25 or 37 degrees C, however, there were no differences in
the protective abilities between the native alpha B-crystallin or the F27R
mutated human alpha B-crystallin. Several other multiple mutations involving
proline residues were also produced. These mutations did not effect the chaperone
like properties of human alpha B-crystallin, but some of them did effect the
native molecular weight size as judged by gel filtration chromatography.
PMID- 9650082
TI - Structural perturbation of alpha-crystallin and its chaperone-like activity.
AB - alpha-Crystallin is a multimeric lenticular protein that has recently been shown
to be expressed in several non-lenticular tissues as well. It is shown to prevent
aggregation of non-native proteins as a molecular chaperone. By using a non
thermal aggregation model, we could show that this process is temperature
dependent. We investigated the chaperone-like activity of alpha-crystallin
towards photo-induced aggregation of gamma-crystallin, aggregation of insulin and
on the refolding induced aggregation of beta- and gamma-crystallins. We observed
that alpha-crystallin could prevent photo-aggregation of gamma-crystallin and
this chaperone-like activity of alpha-crystallin is enhanced several fold at
temperatures above 30 degrees C. This enhancement parallels the exposure of its
hydrophobic surfaces as a function of temperature, probed using hydrophobic
fluorescent probes such as pyrene and 8-anilinonaphthalene-1-sulfonate. We,
therefore, concluded that alpha-crystallin prevents the aggregation of other
proteins by providing appropriately placed hydrophobic surfaces; a structural
transition above 30 degrees C involving enhanced or re-organized hydrophobic
surfaces of alpha-crystallin is important for its chaperone-like activity. We
also addressed the issue of conformational aspects of target proteins and found
that their aggregation prone molten globule states bind to alpha-crystallin. We
trace these developments and discuss some new lines that suggest the role of
tertiary structural aspects in the chaperone process.
PMID- 9650083
TI - Environmental factors influencing the chaperone-like activity of alpha
crystallin.
AB - The effects of mild environmental changes (e.g. the addition of divalent cations
or EDTA, as well as variations of buffer pH) on the heat stability and chaperone
like activity of native alpha-crystallin, and denatured-renatured alpha
crystallin in the native molar isoform ratio, have been investigated using
circular dichroism (CD) spectropolarimetry and functional assays. The presence or
absence of divalent cations has little or no effect on the secondary structure of
renatured samples, although chaperone-like activity levels can vary widely; the
only relevant spectral difference observed is a loss of some alpha-helical
content in all the renatured samples relative to the native protein, but this
change has no impact on function. The range of concentration over which the
inhibitory Mg2+ effect is observed is 10-fold higher for dialyzed fresh protein
than for protein renatured into buffers containing Mg2+, but for both sets of
samples, the full effect is established below physiological Mg2+ concentrations.
Renaturing into various pH buffers, in contrast, affects both heat stability and
chaperone-like activity below pH 7.0, with essentially no functionality observed
at pH 6.0. CD spectra of these samples indicate that acidic conditions lead to
some degree of unfolding, and that this unfolding correlates directly with
functionality. Similar results are obtained for fresh protein dialyzed against
these pH levels. Overall, these results suggest that heat stability is a function
of the protein's secondary structure and folding state, while chaperone-like
activity is primarily a function of factors at the tertiary and quaternary levels
of organization.
PMID- 9650084
TI - Protection of enzymes by alpha-crystallin acting as a molecular chaperone.
AB - How can enzymes function in the centre of a crowded lens over the many decades of
an individual's life when the same proteins are usually turned over in a period
of days or h in most other tissues? The discovery that alpha-crystallin could
function as a molecular chaperone in-vitro has led to the hypothesis that alpha
crystallin could protect enzyme activities against various stresses. In the
laboratory the authors have focused on the effect of alpha-crystallin on the
activity of enzymes upon exposure to a chemical or thermal stress. The authors
have demonstrated that enzymes are rapidly inactivated by sugars, sugar
phosphates, steroids and cyanate. These compounds are elevated in diseases such
as diabetes, diarrhoea and renal failure, all of which are risk factors for
cataract. alpha-Crystallin has been shown to protect specifically against both
chemically- and thermally-induced inactivation. Some enzymes are protected with a
stoichiometry of one or two enzyme molecules protected per alpha-crystallin
aggregate, consistent with a chaperone-like structure. However with other enzymes
a more efficient protection occurs consistent with a micellar structure or
binding on the outside of alpha-crystallin molecules. Investigation of complex
formation indicates that although stable complex formation between enzymes and
alpha-crystallin may be involved in protection of enzymes against thermal
inactivation, protection against chemically-induced inactivation may be more
dynamic in nature.
PMID- 9650085
TI - Phosphorylations of alpha A- and alpha B-crystallin.
AB - In addition to being refractive proteins in the vertebrate lens, the two alpha
crystallin polypeptides (alpha A and alpha B) are also molecular chaperones that
can protect proteins from thermal aggregation. The alpha B-crystallin
polypeptide, a functional member of the small heat shock family, is expressed in
many tissues in a developmentally regulated fashion, is stress-inducible, and is
overexpressed in many degenerative diseases and some tumors indicating that it
plays multiple roles. One possible clue to alpha-crystallin functions is the fact
that both polypeptides are phosphorylated on serine residues by cAMP-dependent
and cAMP-independent mechanisms. The cAMP-independent pathway is an
autophosphorylation that has been demonstrated in vitro, depends on magnesium and
requires cleavage of ATP. Disaggregation of alpha A-, but not alpha B-crystallin
into tetramers results in an appreciable increase in autophosphorylation
activity, reminiscent of other heat shock proteins, and suggests the possibility
that changes in the aggregation state of alpha A-crystallin are involved in yet
undiscovered signal transduction pathways. The alpha-crystallin polypeptides
differ with respect to their abilities to undergo cAMP-dependent phosphorylation,
with preference given to the alpha B-crystallin chain. These differences and
complexities in alpha-crystallin phosphorylations, coupled with the differences
in expression patterns of the two alpha-crystallin polypeptides, are consistent
with the idea that each polypeptide has distinctive structural and metabolic
roles.
PMID- 9650086
TI - Interaction of DNA with bovine lens alpha-crystallin: its functional
implications.
AB - Under normal conditions, lens aggregates of alpha-crystallin subunits, alpha A
and alpha B, are found in the cytoplasm. However, during stress in nonlenticular
tissues, alpha B translocates to the nucleus. A sequence study revealed that both
subunits share a consensus sequence with other DNA binding proteins. These
observations prompted us to investigate DNA binding with alpha-crystallin by UV
mediated photo-crosslinking. The data show that both single and double stranded
DNA crosslink mainly with tetramers of alpha-crystallin subunits. The formation
of tetramers appears to modify alpha-crystallin interactive properties and,
therefore, its induction may have functional significance. These observations
suggest that alpha-crystallin may have a nuclear function which includes DNA
binding.
PMID- 9650087
TI - Evidence for the participation of alpha B-crystallin in human age-related nuclear
cataract.
AB - The aim of this study was to determine if the unusual coloured species
characteristic of age-related nuclear cataract could be localised to specific
residues of the crystallins. The insoluble, crosslinked and coloured cataract
protein fraction (CPF) was isolated from cataract human lenses. Using a
combination of tryptic digestion, gel filtration and multiple reversed phase high
performance liquid chromatography (RP-HPLC), coloured peaks were isolated and
subjected to amino acid sequence analysis. With these techniques, it was hoped to
identify and locate the modified residues. Sequence information was obtained on
16 'coloured' peptides. Many of the peptides were found to be derived from alpha
B-crystallin. When redundancies are taken into account, six distinctive peptides
were found to be derived from alpha B-crystallin; one from beta B1-crystallin,
two from beta A3/A1-crystallin and three from gamma S-crystallin. Three sites of
possible crystallin residue isomerisation to modification were detected in the
alpha B- and beta A3/beta A1-crystallins, including probable asp isomerisation at
residues 25 and 36 in alpha B-crystallin. Since the CPF is unique to nuclear
cataract lenses, these data suggest that alpha-crystallin, and alpha B-crystallin
in particular, may be implicated in the cataract process. This finding supports
that of a recent study on cataract proteins using pronase digestion [Chen YC,
Reid GE, Simpson RJ, Truscott RJW. Exp Eye Res 1997;65:835.]
PMID- 9650088
TI - The possible role of alpha-crystallins in human senile cataractogenesis.
AB - alpha-Crystallins possess molecular chaperone properties and are one of the most
abundant of the lenticular proteins. Posttranslational modifications of these
proteins have been implicated as a possible etiology of human cataracts. This
article will review current knowledge concerning the effects of known
posttranslational modifications upon the molecular chaperone properties and
aggregation behavior of alpha-A and alpha-B crystallin. Based upon these effects,
experimental approaches will be discussed that may be useful in the development
of reagents that may selectively inhibit the cataractogenic process in the aging
human lens.
PMID- 9650089
TI - Recombinant adenovirus encoding gp100 modulates experimental melanin-protein
induced uveitis (EMIU).
AB - Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated
autoimmune uveitis induced by immunization with bovine uveal melanin protein.
Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma
antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has
been used as a vaccine for cancer therapy. This study examines the effect of
Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day
7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV
LacZ), or no virus. On day 21 after immunization, the right eye was processed for
histology and the left eye was analysed for cytokines by quantitative reverse
transcriptase-polymerase chain reaction. Western blot analysis showed that uveal
melanin-protein contains gp100. In three independent experiments, ocular
inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA
was much lower in the rats which received Ad2CMV-gp100 before immunization than
in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in
rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100
injection prevents the development of EMIU, at least in part, through cytokine
regulation.
PMID- 9650090
TI - Inhibition of the development of spontaneous autoimmune thyroiditis in the obese
strain (OS) chickens by in vivo treatment with anti-CD4 or anti-CD8 antibodies.
AB - The involvement of CD4+ and CD8+ T cells in pathogenesis of spontaneous
autoimmune thyroiditis (SAT) in obese strain (OS) chickens has not been studied
in depth until now. We depleted CD4+ or CD8+ T cells in OS chickens by treatment
with murine monoclonal anti-CD4 or anti-CD8 antibodies at 3 day intervals
beginning at hatching. The birds were killed at 19-25 days of age. Treatment with
anti-CD4 antibody completely prevented SAT development, while treatment with anti
CD8 antibody partially inhibited SAT. These results show the critical role of
CD4+ T cells in the development of SAT in OS chickens, and indicate that CD8+ T
cells are also involved in SAT pathogenesis.
PMID- 9650091
TI - Protection from insulin dependent diabetes mellitus afforded by insulin antigens
in incomplete Freund's adjuvant depends on route of administration.
AB - Several islet antigens have been shown to modify the time of onset and severity
of spontaneous insulin dependent diabetes mellitus (IDDM) in NOD (non-obese
diabetic) mice. Oral, intravenous and intra-nasal administration of insulin and
glutamic acid decarboxylase (GAD) or their derived peptides have all been shown
to be effective to differing degrees in reducing the incidence and delaying the
onset of diabetes in this mouse model of the disease. Incomplete Freund's
Adjuvant (IFA) has also played a key role in tolerance when co-administered with
insulin peptides subcutaneously. We show that route of administration may be of
crucial importance, since although insulin B chain and the B9-23 peptide given in
IFA subcutaneously protected (either partially or completely) from IDDM, when
given intraperitoneally they completely failed to modify the disease.
PMID- 9650092
TI - Induction of IgG rheumatoid factor (RF) production by antibody-antibody (RF-like)
immune complexes: the role of T cells, complement and Fc gamma receptors.
AB - Rheumatoid factors (RF) are autoantibodies with specificity for the constant
regions of IgG molecules. They are found in several immunopathological diseases.
The mechanism(s) by which these autoantibodies are produced is largely unknown.
We have previously shown that a single injection of RF-like immune complexes
(ICs) into mice selectively induced an intense IgG1-antibody production with RF
activity. This response was sustained for several months and did not resemble a
conventional immune response to an antigen or other immune complexes. In the
present study, we sought to elucidate the mechanism for the IgG1 RF response to
RF-like ICs. Therefore, the roles of CD4+ T cells, complement and Fc gamma
receptors were analysed. In order to characterize the role of CD4+ T cells, RF
like induced IgG1-RF production was analysed in NZB mice treated with a
monoclonal antibody (mAb) against the CD4 molecule, which resulted in complete
abrogation of IgG1 RF production. To evaluate the importance of Fc gamma Rs, the
effect of RF-like ICs was tested in mice deficient for RF gamma RI/III. A
significant decrease in the numbers of IgG1 antibody secreting cells, as well as
in serum IgG1 RF levels, was found in the deficient mice, as compared with their
normal outbred littermates. The role of complement in RF-like ICs mediated IgG1
RF was tested in complement depleted NZB mice, using Cobra venom factor. The IgG1
RF response in complement depleted and intact mice was comparable. Thus, our
results demonstrate that RF-like immune complexes selectively induce an Fc gamma
R-dependent, complement independent antibody response in mice.
PMID- 9650093
TI - Adhesion elicits an intrinsic defect in interleukin-1 expression by macrophages
from autoimmune-prone MRL mice.
AB - Macrophages (m phi) from prediseased autoimmune-prone MRL/+ and MRL/ lpr mice
have a marked defect in endotoxin (LPS)-induced expression of several cytokines
including interleukin 1 (IL-1). The progressive nature of this defect over time
suggests that it may develop in response to specific extracellular stimuli. In
this report, we show that adhesion is an essential factor for the development of
aberrant IL-1 expression by m phi from autoimmune-prone MRL mice. Thus, when
MRL/+ m phi were allowed to adhere before being stimulated with LPS, they
demonstrated a striking defect in expression of both IL-1 message and protein in
comparison with multiple normal strains. In marked contrast, when MRL/+ m phi
were maintained in a non-adherent state by culture on agarose, the IL-1 defect
was not evident and IL-1 expression was restored to nearly normal levels. Since
an identical defect in IL-1 expression was found when MRL/+ m phi were cultured
on a variety of extracellular matrix proteins (including laminin, fibronectin,
type I collagen, and type IV collagen), it appears that IL-1 underexpression is
dependent on the adhesive state per se rather than on engagement of any one
specific adhesion receptor. Moreover, the cytoskeletal inhibitor cytochalasin D
had no effect on the magnitude of the defect, indicating that the adhesion
dependent signaling events necessary to elicit IL-1 underexpression are
independent of cytoskeletal rearrangement. Taken together, these results indicate
that m phi from autoimmune prone MRL/+ mice have an adhesion-dependent signaling
abnormality that leads to profound underexpression of the cytokine IL-1.
PMID- 9650094
TI - Natural and disease associated autoantibodies to the autoantigen,
dihydrolipoamide acetyltransferase, recognise different epitopes.
AB - Naturally occurring autoantibodies are ubiquitous and may serve physiological
functions. We examined the relationship of natural and disease-associated
autoantibodies in the context of autoantibodies to dihydrolipoamide
acetyltransferase, the 74 kDa E2 sub-unit of the mitochondrial pyruvate
dehydrogenase complex (PDC-E2), characteristic of primary biliary cirrhosis
(PBC). We tested for natural autoantibodies to PDC-E2 in normal sera, and
compared epitopes recognised by natural and disease-associated autoantibodies.
Methods included affinity purification of anti-PDC-E2 from normal and PBC sera,
ELISA and immunoblotting, capacity of antibodies to inhibit the enzyme function
of the pyruvate dehydrogenase complex (PDC), use of F(ab)2 fragments of anti-PDC
E2 in inhibition assays, and testing affinity purified anti-PDC-E2 on peptide
fragments of PDC-E2. We found that natural auto-antibodies to PDC-E2 of IgG class
were demonstrable in all healthy human sera (10/10). However, their reactivity
differed from that of disease-associated autoantibodies, in that anti-PDC-E2 from
normal serum failed to inhibit the catalytic activity of PDC; and F(ab)2
fragments from PBC sera potently blocked the binding of anti-PDC-E2 from PBC sera
to PDC-E2, but not the binding of natural anti-PDC-E2 to PDC-E2. Immunoblotting
on fragments of PDC-E2 using affinity-purified preparations from PBC sera and
normal sera failed to provide evidence for gross differences in epitope
reactivity. We conclude that normal human sera contain natural IgG autoantibodies
to the immunodominant inner lipoyl domain of PDC-E2, as seen characteristically
in PBC. However, there is evidence for differences in fine epitope recognition.
PMID- 9650095
TI - Cross-reactivity of antibodies immunoadsorbed to laminin with recombinant human
La (SS-B) protein.
AB - Anti-La (SS-B) antibodies cross-reacting with mouse B1 laminin were reported in
sera of patients with systemic lupus erythematosus. However, the common epitope
had not been characterized. Immunoblotting conditions were established, allowing
detection and elution of anti-La (SS-B)/laminin cross-reacting antibodies.
Antibodies adsorbed to mouse B1 laminin represented a subclass of anti-La
antibodies. They strongly reacted with human full length recombinant La protein.
However, they failed to react with either an N-terminal La peptide consisting of
amino acids 1-192 or a C-terminal La peptide starting at methionine 223, while
they still reacted with recombinant La peptides consisting of the amino acids 1
341 or starting at 192. These data indicate that the La (SS-B)/laminin epitope is
located between amino acids 192-223 of human La protein, which includes the amino
acids EAKLRA, common to the nuclear autoantigen La (SS-B) and the human or mouse
B1 laminin.
PMID- 9650096
TI - Cloned T cells from a recent onset IDDM patient reactive with insulin B-chain.
AB - Insulin-dependent diabetes mellitus (IDDM) results from selective autoimmune
destruction of insulin producing beta-cells. T-cell reactivity and autoantibodies
to several islet proteins such as insulin, GAD and IA-2 are associated with IDDM
in mice and men. In NOD mice, the majority of T cells from insulitis specifically
recognize the insulin B-chain peptide amino acid 9-22, in contrast to the
periphery where the precursor frequency is much lower. It is important to note
that these cells are diabetogenic. Surprisingly, the same insulin B-chain region
contains epitopes recognized by protective T cells. In fact, autoimmune diabetes
in NOD mice could be prevented by prophylactic treatment with this immunodominant
T-cell epitope. In humans, however, no immunodominant regions of insulin have yet
been defined. We have isolated and characterized a human insulin-specific T-cell
clone that was derived from peripheral blood of a newly diagnosed IDDM patient.
This patient displayed weakly positive primary T-cell responses to insulin. The
peptide recognized by the clone was mapped to the insulin B chain (B:11-27).
Functionally, the human insulin-specific CD4+ T cells displayed a Th1/0 like
cytokine profile and were restricted by HLA-DR. The previously proposed
alternative superantigen-like binding of insulin-B chain peptide outside of the
peptide binding groove of HLA-DR could not be confirmed, since T-cell recognition
was inhibited in competition experiments of insulin-B chain peptide with HLA-DR16
binding influenza peptide HA307-319. Our results indicate that human clonal T
cells isolated from a recent onset IDDM patient recognize an epitope overlapping
with the insulin B-chain region that is immunodominant and potentially
therapeutic in NOD mice. This observation may be useful in studying the role of
insulin-specific T cells in IDDM, and may eventually help to establish peptide
based immunotherapies in IDDM.
PMID- 9650097
TI - The gene responsible for autoimmune polyglandular syndrome type 1 maps to
chromosome 21q22.3 in US patients.
AB - Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple organ
specific autoimmunities such as acquired hypoparathyroidism and autoimmune
Addison's disease, and a predisposition to certain infections such as chronic
mucocutaneous candidiasis. An APS-1 candidate gene was assigned to chromosome
21q22.3 by linkage analyses in patients with APS-1 from Finland. To examine the
influence of ethnic and geographic differences on the location of the candidate
gene locus, we studied 24 US patients with APS-1 by microsatellite marker typing,
using five microsatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18,
selected from chromosome 21q22.3. By allelic association analyses, the
frequencies of allele number 5 for D21S171 and allele number 8 for D21S1903 were
significantly higher in the 24 patients with APS-1 than in 33 controls (33/48 vs.
31/66, P = 0.0207, X2 = 5.35; 12/48 vs. 7/66, P = 0.0418, X2 = 4.15
respectively). The frequency of homozygosity for allele number 5 of D21S171 was
also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P =
0.0078, X2 = 7.07). Maximum lod scores detected for the five markers in nine
families (containing 15 of the patients with APS-1) were: 2.384 for D21S49, 3.144
for PFKL, 3.506 for D21S171, 4.329 for D21S1903, and 1.130 for CD18. These
results confirm the linkage of the candidate APS-1 gene to 21q22.3 in US APS-1
patients, and suggest that the candidate gene is located near the D21S1903
marker. The demonstration of the location of the APS-1 candidate gene to 21q22.3
in an out-bred heterogeneous patient population should promote the physical
mapping of the responsible gene.
PMID- 9650098
TI - Antineutrophil cytoplasmic autoantibodies (ANCA) in children with cystic
fibrosis.
AB - Anti-neutrophil cytoplasmic antibodies (ANCA) represent a useful diagnostic tool
in patients with small vessel vasculitis. Circulating ANCA specific for
bactericidal/permeability increasing protein (BPI) have been recently reported in
adult patients with cystic fibrosis (CF), an autosomal recessive disorder caused
by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene with
consequent impaired function of a transmembrane chloride channel. To contribute
to the better understanding of the significance of ANCA in this disease, we
investigated ANCA presence and antigenic specificity in children with CF. Results
were correlated with clinical status, immunological data, age and genotype. The
indirect immunofluorescence pattern of a total of 71 children with CF indicated
that 31 were c-ANCA positive, while seven were p-ANCA positive. In further ELISA
studies of ANCA antigenic specificity, 51 out of 66 investigated samples were
positive for BPI, and 14 out of 28 were positive for proteinase 3 (PR3). We found
an association between levels of antibodies against PR3 with age and Pseudomonas
infection. We did not, however, find any correlation between CFTR genotypes,
Pseudomonas infection or paediatric parameters and the level of anti-BPI
antibodies. High positivity of anti-BPI antibodies were seen even among the
youngest CF patients, before the development of clinical signs of CF, indicating
that formation of ANCA might be a very early event in the disease. Both anti-BPI
and anti-PR3 antibodies may play a significant, although variable role, in the
pathogenesis of CF.
PMID- 9650099
TI - Response of CD4+ T cells from myasthenic patients and healthy subjects of
biosynthetic and synthetic sequences of the nicotinic acetylcholine receptor.
AB - We investigated the suitability of pools of overlapping synthetic peptides
spanning the complete alpha 1 subunit sequence of the human muscle acetylcholine
receptor (AChR) (alpha 1 pool) or the extracellular domain (residues 1-218, alpha
11-218 pool), and of biosynthetic alpha 1 constructs from E. coli, as stimulants
of human CD4+ cells from myasthenia gravis (MG) patients and healthy subjects. A
construct corresponding to residues alpha 11-209 was obtained as solubilized
inclusion bodies (ib alpha 11-209), or purified by SDS gel electrophoresis (pur
alpha 11-209). A second construct included the extracellular, cytoplasmic and
carboxylterminal domains plus histidine residues, and was obtained as inclusion
bodies (ib alpha 1NoTrans) or purified by gel permeation and histidine tag
affinity chromatography (pur alpha 1NoTrans). A biosynthetic extracellular domain
of the neuronal AChR alpha 7 subunit (ib alpha 71-206) isolated from E. coli as
inclusion bodies served as control for bacterial contaminants. We used ib alpha
11-209, pur alpha 11-209 and peptide pools to propagate CD4+ lines from two MG
patients. The lines obtained using pur alpha 11-209 and the peptide pools
recognized the peptide pools and alpha 1 constructs tested well, but ib alpha 71
206 poorly or not at all. These lines recognized peptides known to form CD4+
epitopes in these patients. The ib alpha 11-209 lines recognized ib alpha 11-209
and ib alpha 71-206 strongly, but recognized poorly pur alpha 11-209 and the
alpha 11-218 pool. We propagated T-cell lines from a healthy subject using pur
alpha 11-209 and ib alpha 11-209. The pur alpha 11-209 line recognized pur alpha
11-209 and the alpha 11-218 pool, but not ib alpha 11-209 or ib alpha 71-206. The
ib alpha 11-209 line recognized ib alpha 11-209 and ib alpha 71-206, but not pur
alpha 11-209 or the alpha 11-218 pool. We tested blood CD4+ cells from six MG
patients and eight healthy subjects with ib alpha 11-209, pur alpha 11-209, the
alpha 11-218 pool and--in the healthy subjects--also ib alpha 71-206, ib alpha
1NoTrans and pur alpha 1NoTrans. In both populations, the alpha 11-218 pool
elicited low and sporadic responses, while the constructs elicited clear
responses that were frequently higher for ib alpha 11-209 than pur alpha 11-209.
The responses to ib alpha 71-206 were strong and comparable to those to ib alpha
11-209, ib alpha 1NoTrans, and pur alpha 1NoTrans. These results indicate that
even purified constructs from E. coli contain bacterial contaminants recognized
by CD4+ cells. They should not be used to test unselected blood CD4+ cells,
because they may evoke strong CD4+ responses to the bacterial antigens. Purified
recombinant sequences may be suitable for propagation of CD4+ cell lines, if the
specificity of the lines can be verified using different antigen preparations.
Short synthetic peptide sequences can be safely used for propagation of specific
CD4+ cells. Although they are poor stimulants for unselected blood CD4+ cells,
the low responses they elicit are probably due to these cells.
PMID- 9650100
TI - ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian,
Anhui Province, China.
AB - ESR and U-series analyses of teeth from the palaeoanthropological site of Hexian
which contained Homo erectus remains, illustrate the limited effectiveness of
stand-alone ESR and U-series age estimates on faunal materials. The problem lies
in the unknown U-uptake history causing very large uncertainties in the age
results of both techniques. This study demonstrates the particular strength that
lies in the integration of ESR and U-series dating analyses allowing the
estimation of the U-uptake history. We obtained a combined ESR/U-series age
estimate of 412 +/- 25 ka (average of six analyses on two teeth). This pinpoints
the deposition of the faunal remains to the time of the transition between oxygen
isotope stages 12 and 11. This is in agreement with the faunal composition which
show a mixture of cold adapted northern mammals and more subtropical-tropical
southern elements. The age also implies that the advanced Hexian Homo erectus
occurred at a similar time as the less advanced Homo erectus specimens at
Locality 1 at Zhoukoudian (LI-LIII).
PMID- 9650101
TI - Archaeological predictions for hominid land use in the paleo-Olduvai Basin,
Tanzania, during lowermost Bed II times.
AB - We present a preliminary predictive model of Oldowan stone artefact and scavenged
larger mammal bone assemblages for 11 landscape facets modeled earlier to occur
across a large portion (> 300 km2) of the paleo-Olduvai Basin during lowermost
Bed II times. This second phase of model-building is based on our earlier
characterizations of the basin's landscape ecostructure and the inter-facet
distribution of key resources and hazards probably encountered by Late Pliocene
hominids (Peters & Blumenschine, 1995, 1996). Our current extension of the model
of hominid-landscape interactions specifies additional theoretical components,
including: (1) the assumed capabilities of Oldowan hominids (presumably Homo
habilis, primarily); (2) the landscape-facet-specific tasks they carried out; (3)
the immediate stone and bone task residues they produced; and (4) the predicted
composition, condition, density, and clustering of stone artefact and butchered
and unbutchered bone assemblages for each facet. We develop ecological linkages
between these new and formerly reported modeling components, the most fundamental
of which is the facet-specific degree of tree/shrub cover abundance, and the
correlated degree of competition among larger carnivores and hominids for
scavengeable larger mammal carcasses. These factors condition variability among
landscape facets in scavenging opportunities encountered by hominids, which in
our model is the major predictor of bone and stone artefact assemblage
composition. The predictive value of scavenging reflects the bias of
paleoanthropological traces toward technology and butchery in their landscape
context, but the model is surprisingly insensitive to what are usually thought to
be critical social components of hominid land use. The predictions for the traces
of hominid-landscape interactions modeled herein can be tested in the future
against the landscape archaeological sample being excavated from lowermost Bed II
by the Olduvai Landscape Paleoanthropology Project.
PMID- 9650102
TI - Theropithecus atlanticus (Thomas, 1884) (Primates: Cercopithecidae) from the late
Pliocene of Ahl al Oughlam, Casablanca, Morocco.
AB - The site of Ahl al Oughlam near Casablanca, Morocco, dated to ca. 2.5 Ma, has
yielded a good sample of Theropithecus atlanticus (Thomas, 1884), a North African
late Pliocene species previously known only by its holotype, a lower molar from
Algeria. Theropithecus atlanticus, which can now be much better defined, is
clearly distinct from other species of the genus, which is thus more diverse than
previously thought. The mandible of T. atlanticus has a very characteristic deep
and long post-molar sulcus and a deep and well excavated supra-lateral triangular
depression of the ramus, with a sharp postero-inferior ridge. The upper and lower
canines are rather large but low. The male P3 is very wide, with well developed
posterior crests; the P4 is rounded, with a large talonid and weak notches and
clefts. Median lingual notches of the lower molars form an acute angle. Although
our incomplete knowledge of T. atlanticus precludes a detailed phylogenetic
analysis, we suggest that it arose by cladogenesis from the T. darti-T. oswaldi
lineage; it is replaced by the latter species in the Pleistocene.
PMID- 9650103
TI - Late Pleistocene human population bottlenecks, volcanic winter, and
differentiation of modern humans.
AB - The "Weak Garden of Eden" model for the origin and dispersal of modern humans
(Harpending et al., 1993) posits that modern humans spread into separate regions
from a restricted source, around 100 ka (thousand years ago), then passed through
population bottlenecks. Around 50 ka, dramatic growth occurred within dispersed
populations that were genetically isolated from each other. Population growth
began earliest in Africa and later in Eurasia and is hypothesized to have been
caused by the invention and spread of a more efficient Later Stone Age/Upper
Paleolithic technology, which developed in equatorial Africa. Climatic and
geological evidence suggest an alternative hypothesis for Late Pleistocene
population bottlenecks and releases. The last glacial period was preceded by one
thousand years of the coldest temperatures of the Later Pleistocene
(approximately 71-70 ka), apparently caused by the eruption of Toba, Sumatra.
Toba was the largest known explosive eruption of the Quaternary. Toba's volcanic
winter could have decimated most modern human populations, especially outside of
isolated tropical refugia. Release from the bottleneck could have occurred either
at the end of this hypercold phase, or 10,000 years later, at the transition from
cold oxygen isotope stage 4 to warmer stage 3. The largest populations surviving
through the bottleneck should have been found in the largest tropical refugia,
and thus in equatorial Africa. High genetic diversity in modern Africans may thus
reflect a less severe bottleneck rather than earlier population growth. Volcanic
winter may have reduced populations to levels low enough for founder effects,
genetic drift and local adaptations to produce rapid population differentiation.
If Toba caused the bottlenecks, then modern human races may have differentiated
abruptly, only 70 thousand years ago.
PMID- 9650104
TI - Multivariate analyses of the hominid ulna from Klasies River mouth.
PMID- 9650105
TI - A newly discovered Kenyapithecus skeleton and its implications for the evolution
of positional behavior in Miocene East African hominoids.
PMID- 9650106
TI - Ethics and law for medical students: the core curriculum.
PMID- 9650107
TI - Palliative care--a euthanasia-free zone?
PMID- 9650108
TI - Reaching targets in the national cervical screening programme: are current
practices unethical?
AB - The principle of informed consent is now well established within the National
Health Service (NHS) in relation to any type of medical treatment. However, this
ethical principle appears to be far less well established in relation to medical
screening programmes such as Britain's national cervical screening programme.
This article will critically examine the case for health care providers
vigorously pursuing women to accept an invitation to be screened. It will discuss
the type of information which women would need in order to make an informed
decision about whether or not to be screened. The lack of such information in
current patient leaflets on the "smear test" will then be documented. Finally,
the article will explore possible ways of maximising women's autonomy in relation
to the cervical screening programme without sacrificing any of its main benefits.
PMID- 9650109
TI - Empirical examination of the ability of children to consent to clinical research.
AB - This study examined the quality of children's assent to a clinical trial. In
subjects younger than 9 years of age, understanding of most aspects of the study
was found to be poor to non-existent. Understanding of procedures was poor in
almost all subjects. In addition, voluntariness may have been compromised in many
subjects by their belief that failure to complete the study would displease
others. If the fact that a child's assent has been obtained is used to justify
the exposure of that child to the potential harm of a non-therapeutic blood
sample, the assent must be meaningful. In the nutrition study observed here, the
quality of the assent of children younger than 9 years of age was very poor. The
assent therefore did not provide a valid justification for requesting a blood
sample from these children. This study indicates that most children younger than
9 years of age cannot be expected to consent or assent to clinical research in a
meaningful way. The current age of 7 years for initiating assent (in addition to
parental consent) is possibly not appropriate and should be reconsidered.
PMID- 9650110
TI - The subtle politics of organ donation: a proposal.
AB - Organs available for transplantation are scarce and valuable medical resources
and decisions about who is to receive them should not be made more difficult by
complicated calculations of desert. Consideration of likely clinical outcome must
always take priority when allocating such a precious resource otherwise there is
a danger of wasting that resource. However, desert may be a relevant concern in
decision-making where the clinical risk is identical between two or more
potential recipients of organs. Unlikely as this scenario is, such a decision
procedure makes clear the interdependence of organ recipient and organ donor and
hints at potential disadvantages for those who are willing to accept but
unwilling to donate organs (free-riders). A combined opting-out and preference
system weakens many of the objections to opting-out systems and may make the
decision to donate organs on behalf of their deceased relatives easier for
families.
PMID- 9650111
TI - Imaginary restrictions.
AB - The role of literature and imagination in medicine and medical ethics is
currently under discussion. This paper argues that the role of literature is not
to furnish generalisable examples for guidance. Rather, engagement with
literature parallels moral engagement with other people. The work of the
imagination, in this context, is not to hypothesise, but to grant life to the
characters and world of literature. In doing this, one may develop one's moral
life.
PMID- 9650112
TI - Narrative and knowledge development in medical ethics.
AB - The role of individual life accounts has been promoted--largely through what has
come to be described as narrative ethics-as important to the practice of medical
ethics for a number of years. Beyond this the apparent incompatibility of
personal stories with scientific procedure has limited their use. In this article
I will argue that this represents a serious under-utilisation of a valuable
method for researching ethical dilemmas and the settings in which these dilemmas
are played out. Life stories need not simply provide a stimulus to scientific
research but can in themselves yield intellectually robust evidence on the
general as well as the particular. By drawing on the rigorous methods developed
elsewhere, personal accounts not only allow us to "enter the world of the sick
person" but allow us to do so in such a way as to contribute to empirical and
theoretical knowledge.
PMID- 9650113
TI - Balancing the quality of consent.
AB - The rule that one must obtain informed consent is well established in medical
ethics and an intrinsic part of clinical practice and of research in biomedicine.
However, there is a tendency that the rule today is being applied too rigidly and
with too little sensitivity to the values that are at stake in connection with
different kinds of research protocols. It is here argued that the quality of
consent needs to be balanced against variables such as degree of confidentiality
and importance of values at stake, in order to be ethically acceptable.
Appropriate information and consent procedures should be adjusted accordingly.
Three levels are suggested, ranging from extensively informed consent with both
written and oral information, through informed refusal with only a limited amount
of information given to, at the other end of the scale, just making relevant
information available.
PMID- 9650114
TI - Teaching medical ethics and law within medical education: a model for the UK core
curriculum.
PMID- 9650115
TI - Ethical dilemmas in occupational therapy and physical therapy: a survey of
practitioners in the UK National Health Service.
AB - OBJECTIVES: To identify ethical dilemmas experienced by occupational and physical
therapists working in the UK National Health Service (NHS). To compare ethical
contexts, themes and principles across the two groups. DESIGN: A structured
questionnaire was circulated to the managers of occupational and physical therapy
services in England and Wales. SUBJECTS: The questionnaires were given to 238
occupational and 249 physical therapists who conformed to set criteria. RESULTS:
Ethical dilemmas experienced during the previous six months were reported by 118
occupational and 107 physical therapists. The two groups were similar in age,
grade, and years of experience. Fifty of the occupational therapy dilemmas
occurred in mental health settings but no equivalent setting emerged for physical
therapy. Different ethical themes emerged between the two groups, with the most
common in occupational therapy being difficult/dangerous behaviour in patients
and unprofessional staff behaviour, and for physical therapists resource
limitations and treatment effectiveness. No differences were found in the ethical
principles used. CONCLUSION: The ethical dilemmas reported by the therapists were
primarily concerned with health care ethics, rather than the more dramatic ethics
reported in much of the biomedical ethics literature. Differences were found
between the two professional groups when ethical contexts and themes were
compared but not when ethical principles were compared. This suggests that
educators and researchers need to be aware of work settings and the
interdisciplinary nature of employment as well as ethical principles held by
individual therapists.
PMID- 9650116
TI - Limits of neonatal treatment: a survey of attitudes in the Danish population.
AB - OBJECTIVES: To study attitudes in the Danish population towards treatment of
severely handicapped and extremely preterm infants and to define areas of
consensus and controversy. DESIGN: Mail-delivered questionnaire. SETTING:
Denmark. Survey sample--A random sample of 1080 persons aged from 18 to 45 years.
RESULTS: The overall response rate was 68%. There was strong consensus (more than
75% agreement) that life-prolonging treatment should be provided for an infant
born after 24 weeks' gestation with respiratory distress and, for an infant with
myelomeningocele, when the parents were in favour of treatment. Further, there
was almost uniform agreement that not all infants should be treated no matter how
serious the condition. Major controversies concerned the severity of a condition
needed to justify omission of life-prolonging treatment, the role of parental
attitude and the options in non-treatment cases. Forty-six per cent thought it
ought to be legal to kill the infant in at least some of these cases. CONCLUSION:
Although the study revealed wide divergences of opinion with regard to questions
about limits of treatment and about end-of-life decisions it also showed that
there was general acceptance both that life-prolonging treatment ought to be
provided even in relatively severe cases if this was in accordance with parental
wishes, and that life should not be saved at all costs.
PMID- 9650117
TI - Is there a demand for a clinical ethics advisory service in the UK?
PMID- 9650118
TI - ACE-inhibitors and progression of chronic renal insufficiency: a contribution of
Italian clinical research.
PMID- 9650119
TI - Neutrophils and acute ischemia-reperfusion injury.
AB - Leukocyte infiltration in response to I/R injury is a well-known but poorly
understood phenomenon. The contribution of neutrophils in this process is still
controversial. Despite numerous data, little is known about exact numbers of
infiltrating neutrophils. The role of monocytes/macrophages in this process is
even more unclear. The role neutrophils in the kidney and other organs was
reviewed. The variability in models and methods for neutrophil quantification
were examined, along with carrying out a critical overview of depletion and anti
adhesion approaches. Nevertheless, the exact role attributed to neutrophils in
the I/R process remains unclear.
PMID- 9650120
TI - Ischemic disease of the kidney: how and why to consider revascularization.
AB - With increasingly accurate non-invasive tests, the clinician frequently discovers
obstruction of the renal arteries by atherosclerosis. The decision to reverse
this obstruction is not straightforward, particularly when blood pressure can be
easily controlled with medications. Proper management of this problem requires
knowledge of the accuracy of the diagnosis, the natural history of the disorder,
and the outcomes of possible interventions. This review will emphasize the value
of a variety of non-invasive tests, the consequences of allowing the arteries to
remain obstructed, and the long-term results from reversing renal artery
obstruction. Surgical and non-surgical interventions will be examined, including
percutaneous angioplasty, angioplasty with wall stenting, surgical atherectomy,
and surgical bypass procedures. In contemporary practice hypertension is
routinely recognized and aggressively treated regardless of the etiology.
Therefore preservation of kidney function is becoming an increasingly important
clinical goal. This review will pursue a unified approach to renal artery
obstruction and emphasize the goal of preserving glomerular filtration rate.
PMID- 9650121
TI - Surgical complications of kidney transplantation.
AB - Over the last 30 years, kidney transplantation has evolved tremendously, from an
experimental procedure with barely 50% allograft acceptance to a highly refined
management program with a success rate of 80-90%. Not only has the overall rate
of complications decreased to less than 5%, due to more secure technical
approaches, but also advances in immunosuppressive regimens have reduced the
morbidity associated with the procedure. This contribution, addressing all stages
of the transplant process (donor nephrectomy, benchwork preparation, and
implantation) assesses potential pitfalls and technical misadventures that must
be avoided in order to assure the patient of a complication-free course.
PMID- 9650122
TI - Absence status: an overlooked cause of acute confusion in hemodialysis patients.
AB - Epileptic seizures are a known complication of uremia, but non-convulsive
seizures appear to be rare. We describe a patient with absence status presenting
with acute confusion who responded well to intravenous diazepam. Attention is
drawn to this rare cause of acute confusional state in the hemodialysis
population.
PMID- 9650123
TI - Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal
Diseases Registry.
AB - There is little data on the spectrum of renal diseases in the United Arab
Emirates. A renal diseases registry has been set up in an attempt to address this
issue nationwide, and we report here the first outcome of this endeavor, a
retrospective histopathologic analysis of 490 native kidney biopsies performed on
adult patients presenting to four hospitals in the Emirate of Abu Dhabi from 1978
to June 1996. The most common indication for a biopsy was the nephrotic syndrome
(54.0%), followed by asymptomatic urinary abnormalities (29.7%), and chronic
renal failure (12.7%). Primary glomerular disease accounted for 77.1% of all
biopsies. Chronic proliferative glomerulonephritis as a group was the predominant
pathology (36.2%), followed by idiopathic membranous glomerulopathy (20.1%),
focal segmental glomerulosclerosis (18.3%), minimal change nephropathy (18.3%),
and IgA nephropathy (6.3%). Of the patients with secondary kidney diseases, 33
(40.7%) had systemic lupus erythematosis, 27 (33.3%) amyloidosis, 14 interstitial
nephropathy, and seven diabetic nephropathy. Kidney biopsies of 187 patients with
primary glomerular disease who presented with the nephrotic syndrome were
analyzed. In this group idiopathic membranous glomerulopathy, proliferative
glomerulonephritis, and minimal change glomerulopathy was found in almost equal
proportions (28.3%, 26.6%, 26.2%) with focal segmental glomerulosclerosis (15.4%)
accounting for the bulk of the remainder. Though the overall results of this
analysis do not show any major differences in the spectrum of primary
glomerulopathies in the United Arab Emirates compared with other countries, a
slight tendency towards a higher frequency of focal segmental glomerulosclerosis
among patients indigenous to the Arabian Peninsular (20.4%) deserves further
evaluation.
PMID- 9650124
TI - The nonselective adenosine antagonist theophylline does prevent renal dysfunction
induced by radiographic contrast agents.
AB - Radiocontrast agents (RCA) induce nephrotoxicity characterized by acute renal
failure (ARF), which seems to be mediated partly by adenosine. ARF significantly
influences erythropoietin (EPO) secretion and plasma renin activity (PRA). The
present study assessed the influence of theophylline, a nonspecific adenosine
receptor antagonist, on renal function, EPO secretion and PRA after the use of
RCA. Fifty-eight patients underwent X-ray examinations with administration of
RCA. Patients were randomized to receive either 165 mg of theophylline or placebo
(saline) before the injection of 40 ml of high-osmolar contrast medium Plasma
concentrations of EPO and PRA were assayed in blood samples drawn 2 hours before
and 3, 6, 12 and 24 hours after RCA. Glomerular filtration rate, evaluated from
endogenous creatinine clearance, urinary excretion of beta 2-microglobulin (beta
2-M), Tamm-Horsfall protein (THP) and albumin were assessed one day before RCA,
on the day of RCA injection and one day later. In patients not treated with
theophylline, RCA injection was followed by a significant reduction of GFR and
increased urinary excretion of both beta 2-M and THP, which declined or were
normal one day later. Simultaneously there was a significant decrease of plasma
EPO and PRA. Theophylline prevented the decline of GFR, the increase of urinary
beta 2-M and THP and the reduction of plasma EPO and PRA. The drug did not
influence urinary albumin excretion. We conclude that RCA-induced impairment of
renal excretory, endocrine and tubular function can be prevented by giving
theophylline before RCA. These results suggest that adenosine may play a role in
the pathogenesis of RCA-induced nephropathy.
PMID- 9650125
TI - Intravenous immunoglobulin induced-nephropathy: a complication of IVIG therapy.
AB - Since the early 1950s, intravenous immunoglobulin (IVIG) preparations are being
used in the treatment of hematologic, neurologic, nephrologic, autoimmune, and
immunodeficiency disorders. Infusion of IVIG preparations may cause osmotic
induced acute renal failure. Despite the fact that this entity has been reported
previously, it is not a widely appreciated complication. A total of 22 reports
involving 52 patients in whom renal failure occurred in association with IVIG
infusion. The patients' ages ranged from 20 to 82 years. Thirty patients had
preexisting renal insufficiency. Rise in serum creatinine was noted after 1-10
days of IVIG infusion and creatinine returned to baseline within 2-60 days of
discontinuation. One developed end stage renal disease. There were four
fatalities related to complications of renal failure. Histopathology of renal
tissue showed osmotically induced tubular injury (5 patients), tubular
vacuolization (2 patients), tubulointerstitial infiltrate (1 patient), and
cryoglobulin deposits (1 patient). There appears to be no direct relationship
between the development of acute renal failure and the type of IVIG. However,
underlying renal insufficiency increases the risk of renal failure. In view of
the increasing use of IVIG preparations in medicine, it is imperative that
clinicians be aware of this unusual form renal injury.
PMID- 9650126
TI - Obstetric outcome in women who present with a reduction in fetal movements in the
third trimester of pregnancy.
AB - A complaint of decreased fetal movements is a common indication for the
assessment of fetal well being. The aim of this study was to review the outcome
of a group of women whose primary indication for referral was decreased fetal
movements. Over a 20 month period, 435 patients were seen in the fetal assessment
unit of an inner London teaching hospital, following a primary complaint of
reduced fetal movements. Investigations included: the fetal abdominal
circumference (AC), amniotic fluid volume (AFV), the umbilical artery pulsatility
index (UAPI) derived from Doppler ultrasound waveforms and a computerised
analysis of fetal heart rate (FHR) recordings or cardiotocograph (CTG). Outcome
measures were: gestational age at delivery, Apgar score < 7 at 5 minutes,
admission to the Special Care Baby Unit (SCBU), the need for delivery by an
emergency cesarean section for fetal compromise (CSFC), and any perinatal deaths.
A comparison of actual versus expected outcome for women with decreased fetal
movement revealed the following relative risks, with the 95% confidence intervals
(CI) in brackets; low 5 minute Apgar score 0.03 vs. 0.05 expected (CI = 0.01,
0.05), SCBU admission, 0.06 vs. 0.07 (0.04, 0.08), and preterm delivery, 0.08 vs.
0.11 (0.05, 0.10). Cesarean sections for fetal compromise, 0.07 vs. 0.053 (0.050
0.096). The addition of FHR monitoring to standard ultrasound assessment of well
being did not appear to confer any added benefit. There were no fetal deaths. The
outcome for pregnancies where the mother presents with decreased fetal movements
in the third trimester is comparable with the outcome for the general population.
PMID- 9650127
TI - Quality assessment of two lactate test strip methods suitable for obstetric use.
AB - Accuracy of lactate determinations in cord blood was tested for one
reflectometric (Accusport) and one amperometric (Lactate Pro) microvolume test
strip lactate meter. Both meters, using a whole blood sample, measure lower
levels of lactate than a reflectometric device considered as a reference method,
which analyses lactate in plasma. Readings were unaffected irrespective of
lactate concentrations for the Lactate Pro, whilst the Accusport overestimated
low lactate concentrations and underestimated high values. Both lactate meters
underestimated lactate concentrations at high hematocrits, as compared with the
reference method. The Lactate Pro has a fixed sample volume of 5 microliters
while the Accusport uses random blood drop as sample volume. However, in analyses
with less than 20 microliters sample volume considerable underestimation was
found with the Accusport. Coefficient of variation was 3.8-8.9% for the Accusport
and 3.1-4.0% for the Lactate Pro within lactate concentrations between 2.1 and
5.3 mmol/l. The amperometric device, the Lactate Pro, performed best in these
tests dealing with fetal blood lactate concentrations. The new technique can be a
useful tool in perinatal research as well as in obstetric practice.
PMID- 9650128
TI - Comparison of maternal and cord blood polymorphonuclear leukocyte elastase
levels.
AB - The main objective of this study was to examine the influence of parturition on
the polymorphonuclear leukocyte elastase release in the fetus and the mother.
There were 32 babies and parturients. The mean arterial cord blood elastase level
was 294.8 +/- 129.15 ng/ml (median 304.25), while the mean plasma (venous) level
in the adult normal controls was 35.66 +/- 14.1 ng/ml. The difference was highly
significant at p < 0.0001 (Student's t test, two-tailed). The mean elastase level
of the mothers was 143.45 +/- 109 ng/ml (median 115.25). This was significantly
lower than the mean arterial cord blood elastase level (p < 0.0001) but higher
than the mean elastase level in healthy adults (p < 0.0001). The mean cord blood
and the mothers' white blood cell counts were 11.9 +/- 3.1 (median 11.8, range
6.3-18.7 x 10(9)/l) and 12.4 +/- 2.8 (median 12.4, range 7.3-17.1 x 10(9)/l)
respectively. The difference was not statistically significant (p = 0.4). The WBC
counts correlated significantly with the mothers' (r = 0.4, p = 0.03) and cord
blood (r = 0.7, p < 0.0001) elastase levels. These results suggest that the
raised arterial cord blood elastase levels during parturition may reflect the
disturbance of fetal homeostasis during parturition.
PMID- 9650129
TI - Risk factors for neonatal sepsis in offspring of women with prelabor rupture of
the membranes at 34-42 weeks.
AB - One thousand three hundred eighty-five women with PROM (prelabor rupture of the
membranes) participated in a prospective randomized study. Women with PROM were
randomized to induction the following morning after PROM (early induction group)
or induction two days later (late induction group). If contractions started
within 2 hours after admission these women were included in the short latency
group. All neonatal infections were classified as verified sepsis (positive
culture) or clinical sepsis. The aim of the study was to compare the perinatal
infectious outcome between the groups with different expectant managements in
women with PROM and to study the association between demographic, intrapartum and
postpartum variables and neonatal sepsis. In the short latency group one neonate
had a proven sepsis while four neonates with proven sepsis were found in the
early induction group. No proven sepsis was detected in the late induction group.
Univariate analyses showed a significant association between clinical sepsis and:
induction of labor (OR = 2.94, 95% CI 1.30-6.68), established labor 24.1-32 hours
after ROM (OR = 5.89, 95% CI 1.68-20.63), established labor > 32 hours after ROM
(OR = 4.59, 95% CI 1.52-13.87), time from ROM to delivery > 32 hours (OR = 5.07,
95% CI 1.40-18.39), cesarean section (OR = 11.03, 95% CI 4.10-29.68),
chorioamnionitis before or during delivery (OR = 27.14, 95% CI 2.38-309.16),
endometritis (OR = 18.08, 95% CI 1.82-179.87), CRP over 20 mg/l in the umbilical
cord (OR = 17.12, 95% CI 5.68-52.12) and Apgar score < 7 after 1, 5 or 10
minutes. In a stepwise logistic regression analysis a significant association was
found between clinical sepsis and cesarean section (OR = 10.08, 95% CI = 3.26
31.20), time from ROM to delivery > 32 h (OR = 3.74, 95% CI 1.62-8.62),
gestational age 34-36 weeks (OR = 3.16, 95% CI 1.11-8.96) and parous women (OR =
2.41, 95% CI 1.04-5.57). In conclusion, this study indicates that that there was
no difference in the incidence of neonatal infections between those with early
and late induction. Clinical neonatal sepsis was associated with time from PROM
to delivery over 32 hours, cesarean section, parous women and gestational age
between 34 and 36 weeks.
PMID- 9650130
TI - Computerised analysis of fetal heart rate recordings in patients with diabetes
mellitus: the Dawes-Redman criteria may not be valid indicators of fetal well
being.
AB - Computerised cardiotocograph analysis has been used in our medical antenatal
clinic for women with insulin dependent diabetes mellitus for five years. We had
observed that many of the patients failed the computer criteria and wished to
examine this finding in more detail. All cardiotocographs from 40 pregnant women
with insulin dependent diabetes mellitus who delivered between 1992 and 1995 were
reviewed. The number of traces failing the criteria were calculated. Outcome was
compared between patients with a normal trace and those with an abnormal trace.
233 recordings were examined. 30.5% of antenatal CTGs failed the criteria because
of absent high episodes of variation (a parameter which is a specific marker of
fetal well-being). After excluding repeat traces on all patients a sample of 26
traces was examined. 34.6% of these had failed because of absent high episodes of
variation. Both these figures are significantly higher than the published normal
values. There was no apparent difference in neonatal outcome between women whose
trace had failed (9) and those with a normal trace (17). We suggest that the
normal values of criteria used to analyse computerised CTGs may not be valid when
applied to fetuses of women with diabetes mellitus.
PMID- 9650131
TI - Cerebral Doppler blood flow velocimetry and central hemodynamics in the ovine
fetus during hypoxemia-acidemia.
AB - The purpose of this study was to assess the effects of hypocapnic hypoxia,
acidemia and the combination of hypoxia/acidemia on blood flow velocity variables
in the fetal cerebral circulation. Chronically instrumented fetal sheep were used
and the ewes were induced to breathe a hypoxic gas mixture for about 90 min. This
caused an initial period of hypoxemia followed by a period of mixed
hypoxemia/acidemia. When the ewe was reoxygenated, the fetus experienced a period
of normoxic acidemia. The fetal cerebral circulation was assessed by recording
Doppler blood flow velocity waveform variables in a cerebral vessel and the
umbilical artery, using standard ultrasound equipment. External carotid artery
blood flow was maintained during hypoxic and hypoxic/acidotic periods despite a
fall in cardiac output. In the cerebral vessel, mean maximum velocity (time
averaged maximum velocity), minimum diastolic velocity and maximum systolic
velocity manifested increases during hypoxic and hypoxic-acidotic periods, but
pulsatility index did not change due to the effect of reduced heart rate on
pulsatility index. Umbilical artery pulsatility index increased in the hypoxic
and hypoxic-acidotic periods, despite unchanged mean maximum velocity, minimum
diastolic velocity and maximum systolic velocity. With acute hemodynamic changes,
the measurement of pulsatility index can yield misleading results. For clinical
and experimental research on the fetal cerebral circulation, more attention
should be paid to the individual Doppler variables, especially to the mean
maximum velocity, than to the pulsatility index alone. Changes in mean maximum
velocity recorded from the cerebral artery seem to reflect changes in the
cerebral arterial flow.
PMID- 9650132
TI - Effects of magnesium sulfate infusion upon clotting parameters in patients with
pre-eclampsia.
AB - The objectives of this study were to evaluate the possible mechanisms involved in
prolongation of bleeding time in pre-eclamptic patients receiving a magnesium
sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near
term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied.
Fifteen of them received magnesium sulfate infusion; 3 did not and served as
controls. Bleeding time (modified Ivy method with Surgicutt), platelet count,
platelet aggregation pattern, as well as serum arachidonic acid metabolites
[thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)]
werde done on admission to the labor floor (before magnesium infusion) and
repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls
received the second test 24 hours postpartum. Thirteen of 15 patients receiving
magnesium sulfate had an increase in bleeding time from an average of 6 minutes
31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a
decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6
minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams.
Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet
aggregation pattern done in 11 patients and was normal and unchanged after
magnesium in 10 of the patients with increased bleeding time and one control.
TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after
magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695
and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did
not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation
between duration of infusion or total magnesium given and directions of small
changes observed. This study confirms a prior preliminary observation that
magnesium sulfate infusion, as currently used to prevent eclamptic convulsions,
induces a significant prolongation of bleeding time. This effect is mediated
neither by changes in platelets count or aggregation pattern, nor by changing the
level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1
alpha). Further studies are needed to clarify the mechanism of this clinically
important observation of increased bleeding following magnesium sulfate infusion.
PMID- 9650133
TI - The umbilical ring--the first rapid in the fetoplacental venous system.
AB - In this study, the effect of the umbilical ring on blood flow velocities in the
umbilical vein was examined using Doppler sonography. The maximum blood flow
velocity in the umbilical vein was measured just before and behind the umbilical
ring in eleven normal singleton pregnancies at 24-34 gestational weeks. The
maximum velocity increased in each single case (p < 0.0001), the mean increase
was from 16 cm/sec to 31 cm/sec. Thus, the narrowing of the umbilical ring serves
as the first rapid in venous fetoplacental circulation. The physiological role of
the acceleration of venous blood flow remains to be elucidated. Possible
functions include stabilizing venous blood flow or preferential streaming.
PMID- 9650134
TI - A simple technique to isolate DNA and supernatant of genital Mycoplasma hominis
and Ureaplasma urealyticum.
AB - Vaginal colonization with Mycoplasma hominis and Ureaplasma urealyticum has been
implicated as a cause of prematurity. Several mechanisms to induce preterm labor
have been discussed. The investigation of expressed and secreted enzymes requires
a feasible method for culturing and further processing of these bacteria. We
describe a simple technique for culturing of Mycoplasma hominis and Ureaplasma
urealyticum without contamination with other microorganisms and isolating DNA and
supernatant. PCR amplification of a chromosomal Mycoplasma fragment was performed
as positive control.
PMID- 9650135
TI - Cervical balloon for dysfunctional labor following amniotomy.
AB - The conventional treatment for arrest of protracted active phase dilatation is
amniotomy and oxitocin. This kind of labor dystocia is associated with an
increased incidence in Cesarean delivery. We describe the use of cervical balloon
after amniotomy for protracted active phase dilatation. We have used this
approach in five parturients. All five patients had a spontaneous vaginal
delivery. Intrapartum cervical balloon in patients with dysfunctional labor may
reduce the need for Cesarean delivery.
PMID- 9650136
TI - Effective drug treatment. Testing the distal needs hypothesis.
AB - A long-standing view held by many drug abuse treatment providers, researchers,
and policy makers is that maximally effective drug treatment needs to attend to
the employment, health, housing, and other "distal needs" of the client. This
paper tests the distal needs hypothesis by determining the effects of resolved,
unresolved, and emergent family, housing, health, legal, emotional, and
vocational needs on treatment engagement and treatment outcomes. Findings from a
prospective, longitudinal study of 330 clients in 26 outpatient programs in the
Los Angeles metropolitan area indicate little support for the distal needs
hypothesis. Specifically, those with unresolved or emergent distal needs were not
less likely to engage in treatment or use drugs during and after treatment.
Treatment and research implications of these findings are addressed.
PMID- 9650137
TI - The Teen Treatment Services Review (T-TSR).
AB - This report describes the Teen-Treatment Services Review (T-TSR) and its initial
testing. This brief interview modified from the adult Treatment Services Review
(McLellan et al., 1992) furnishes a quantitative profile of the types and number
of in-program and out-program treatment services provided during a treatment
episode for substance use disorders (SUD). One-day test-retest interval data were
collected from adolescent patients in a partial hospitalization program (PHP, N =
20) and from an outpatient clinic (OPA, N = 24). The clinical utility is
supported. The test-retest reliabilities of the T-TSR were variable. The T-TSR
may be useful at the programmatic level in describing and comparing programs by
the type and number of services delivered to adolescents with SUD. Additionally,
it may offer a tool for quality assessment by evaluating actual patient treatment
services matching. Further studies of the psychometric properties of this
instrument in various clinical settings for adolescents are recommended.
PMID- 9650138
TI - Measuring treatment process beliefs among staff of specialized addiction
treatment services.
AB - In a survey conducted in Ontario, front-line staff of specialized addiction
treatment services were asked to indicate the extent to which they believed 53
different treatment processes to be necessary for the effective treatment of
people with alcohol and drug problems. Cognitive-behavioural processes were
generally rated as almost essential for treatment to be effective. Other
processes received mixed ratings, while confrontation and pharmacological
treatment were, on average, rated as detrimental. Factor analysis identified
three interpretable dimensions of beliefs (a) cognitive-behavioural, (b) disease,
and (c) medication. A fourth dimension involved both psychodynamic and
conditioning processes and did not clearly correspond with any known therapeutic
approach. Scores on scales developed using items from these four dimensions were
variously influenced by respondents age, education, place of work, and
certification status. Two groups identified using cluster analysis differed
primarily with respect to scores on the disease scale. Logistic regression
analysis showed that age, certification status, and place of work were associated
with membership in these groups. Implications for treatment system development
and research are discussed.
PMID- 9650139
TI - Smoking cessation for clients in chemical dependence treatment. A demonstration
project.
AB - A demonstration project was conducted to examine the factors that facilitate
implementation of nicotine dependence treatment in a chemical dependence (cd)
program. The project included: (a) staff education; (b) staff training to conduct
nicotine dependence treatment groups; (c) voluntary smoking cessation treatment
for smoking staff; and (d) smoking cessation treatment for client volunteers in
outpatient and residential cd programs. A 12-week, cognitive/behavioral group
program with nicotine patches was conducted separately for staff and client
volunteers. Forty-two of approximately 70 staff returned smoking questionnaires,
10 of whom reported current smoking. Four staff members began treatment, in
addition to four staff from a second treatment agency. There were three of eight
staff (37.5%) who reported ongoing abstinence at the end of the 12-week program.
There were 83 cd clients (approximately 20% of smoking clients) who volunteered
to participate in smoking cessation treatment. Forty clients began treatment, 3
(7.5%) of whom were abstinent from smoking at the conclusion of the 12-week
program. Staff smoking, lack of clinic resources devoted to the project, and
voluntary client participation, which was adjunctive to other treatment
components, were impediments to implementation and success. Success was greatest
in a clinical setting in which smoking cessation treatment was staff supported
and integrated with cd treatment. We recommend that (a) smoking cd staff be
offered nicotine dependence treatment, (b) nicotine dependence treatment become a
standard, integrated component of cd treatment, and (c) initiation of smoking
cessation be individualized according to clients' needs and circumstances.
PMID- 9650140
TI - Types of abuse and cocaine use in pregnant women.
AB - Previous research has found an association between childhood and adult physical
and sexual abuse and substance abuse, but has not examined or compared specific
dimensions of the abuse experience, such as its age of onset or the type,
severity, or frequency. Women receiving perinatal care (N = 1189) at an inner
city hospital clinic were systematically questioned about their lifetime and
current cocaine use and experiences of abuse. We found an association between a
history of abuse in childhood and lifetime and current cocaine use, as well as
physical and sexual abuse during childhood and pregnancy. There was no difference
in the rates of cocaine use between women whose onset of abuse was in childhood
versus adulthood. Childhood sexual abuse (alone or in combination with physical
abuse) was more associated with lifetime cocaine use than was physical abuse
alone. Cocaine use was related to the severity, but not the frequency of abuse.
PMID- 9650141
TI - Stories of spiritual awakening. The nature of spirituality in recovery.
AB - Substance abuse has had a devastating impact on the lives of millions. As
substance use and abuse continues to ravage communities, researchers remain in
the dark about what works to ensure successful recovery from addiction. In
searching for the answers, researchers have often overlooked the role of
religious and spiritual practices and beliefs in preventing use and relapse. The
study reported here describes the process of spiritual awakenings experienced by
some persons in recovery during their quest for sobriety. The data suggests that
persons in recovery often undergo life altering transformations as a result of
embracing a power higher than one's self, that is, a Higher Power. The result is
often an intense spiritual journey that leads to sustained abstinence. Given how
widespread substance abuse is, research on the nature, implications, and
limitations of a spiritual approach to addiction might offer new options for
treatment.
PMID- 9650142
TI - The ARISE Intervention. Using family and network links to engage addicted persons
in treatment.
AB - An alternative method to the Johnson Institute's "Intervention" is presented
which, while incorporating many of Johnson's innovations, is, additionally: (a)
less confrontative, thereby avoiding the reactivity in clients and family members
that such confrontational approaches have tended to evoke; (b) takes into account
both the needs of the chemically dependent person as well as the needs of the
larger family and network system; and (c) aimed toward enrolling substance
abusers in outpatient (as well as inpatient) treatment, thus placing it more in
line with managed care priorities. Principles for treatment engagement are
presented, accompanied by case examples. The approach is part of a more
comprehensive model designed to maximize successful engagement with a minimum
amount of professional time and effort.
PMID- 9650143
TI - Perceptions of the supervisory relationship. A preliminary qualitative study of
recovering and nonrecovering substance abuse counselors.
AB - Interviews with a sample (N = 5) of substance abuse counselors were conducted
concerning perceptions of their relationship with their clinical supervisors. The
interview protocol was developed from four existing supervision relationship
inventories, with an additional group of questions concerning satisfaction with
supervision. Significant themes were determined from the examination of interview
data. In addition, the supervisory relationship responses were compared to
responses about supervisee satisfaction with supervision. Salient themes also
were compared based upon counselor and supervisor substance abuse recovery
status. The significance of recovery within the supervisory relationship is
discussed as well.
PMID- 9650144
TI - Suicide attempts, substance abuse, and personality.
AB - The prevalence and relevance of a positive suicide attempt history among 103
subjects who had entered a substance abuse program and participated in a study of
personality was examined. Twenty subjects had a positive suicide attempt history.
Women were more likely to attempt suicide. Attempters were more likely to have
additional psychiatric diagnoses, such as major depression. Attempters had higher
addiction severity scores, abused more substances, and were more likely to have
abused alcohol and sedative hypnotics than were nonattempters. DSM-III-R and
Eysenck personality measures were compared across groups. Attempters had
significantly higher neuroticism and borderline scores. Impulse dysregulation may
predispose this group to more severe addictions.
PMID- 9650145
TI - A review of systematic and quantifiable methods of estimating the needs of a
community for alcohol treatment services.
AB - The purpose of this paper was to review a variety of systematic and quantifiable
methodologies for planning and evaluating the provision of alcohol treatment
services for communities. These methods include: (a) developing and evaluating
indicators of alcohol-related harm in and across defined geographic areas, to
assess the relative need for services; (b) demand-oriented techniques that
involve the prediction of future demand for services based on the previous
utilisation of treatment facilities; (c) comprehensive systems approaches to
planning services; and (d) the estimation of the prevalence of individuals who
need or would benefit from an intervention for their alcohol problem. In
practice, service planners may incorporate a combination of approaches that could
be compared and contrasted to assess the convergent validity of results. These
methodologies can also be used to provide information for planning and evaluating
prevention/health promotion and early intervention initiatives.
PMID- 9650146
TI - Accountability in public short-term adult AOD residential treatment.
Fontainebleau Treatment Center.
AB - Fontainebleau Treatment Center provides short-term public residential AOD
treatment and primary health care to a lower-socioeconomic adult population. The
multimodal focus of treatment includes interactive group therapy, behavioral
contracting, relapse prevention, and 12-step involvement. Research funded by the
National Institute on Drug Abuse indicated both positive treatment outcome and
significant cost efficacy. These results may be in some contrast to prevailing
assumptions about public sector, government-operated behavioral health-care
delivery to high-risk populations. Multiple variables for consideration in future
outcome research are discussed, with potential for database inclusion toward
standardization of treatment and cost protocols.
PMID- 9650147
TI - Shouting 'cure!'--or whispering 'hope'--in a crowded cancer ward.
PMID- 9650148
TI - Research funding and cloning: top recent policy agenda.
PMID- 9650149
TI - Promoting the health and wellness of women with disabilities.
PMID- 9650150
TI - Pamphlets for your patients: diabetes.
PMID- 9650151
TI - Toward optimal health: the experts discuss tamoxifen and breast cancer
prevention. Interview by Jodi Godfrey Meisler.
PMID- 9650152
TI - Soy: just a hill of beans?
PMID- 9650153
TI - A review of the effectiveness of Cimicifuga racemosa (black cohosh) for the
symptoms of menopause.
AB - In this review of eight human studies on the effectiveness of an extract of
Cimicifuga racemosa on alleviating menopausal symptoms, it is apparent that it is
a safe, effective alternative to estrogen replacement therapy for those patients
in whom estrogen replacement therapy is either refused or contraindicated.
PMID- 9650155
TI - Female gender as a risk factor for drug-induced cardiac arrhythmias: evaluation
of clinical and experimental evidence.
AB - One of the most pronounced gender-based differences in response to drugs is
women's far greater risk of developing the life-threatening ventricular
arrhythmia called torsades de pointes (TdP). A review of the literature and
databases of the Food and Drug Administration reveals that a much higher
percentage of women than men develop TdP arrhythmias after taking a variety of
drugs, such as antihistamines (terfenadine, astemizole), antibiotics
(erythromycin), antimalarials (halofantrine), antiarrhythmics (quinidine, d
sotalol), and miscellaneous other drugs. All of these drugs have in common the
ability to block potassium currents, thereby prolonging cardiac repolarization
and the QT interval on the ECG. The available experimental data support the
hypothesis that gender differences in specific cardiac ion current densities are
responsible, at least in part, for the greater susceptibility of females for
developing TdP arrhythmias. In isolated perfused rabbit hearts (Langendorff
technique), female rabbit hearts display greater baseline and drug-induced
(quinidine and d-sotalol) changes in QT intervals than male hearts, and at least
two different repolarizing potassium current densities (IKr and IKl) are found to
be significantly lower in ventricular cardiomyocytes from female rabbits compared
with those from males. Thus, it appears that as in humans, clear gender
differences exist in the electrophysiologic characteristics governing cardiac
repolarization in rabbits. This model and perhaps others should be examined as
predictors of functional and pharmacologic differences between men and women.
Understanding the potential mechanisms responsible for the greater risk of drug
induced arrhythmias in women could lead to screening methods for identification
of individuals at risk for drug-induced arrhythmias or to the development of
drugs with reduced risk of inducing arrhythmia.
PMID- 9650154
TI - Genetic testing for BRCA1 and BRCA2: recommendations of the Stanford Program in
Genomics, Ethics, and Society. Breast Cancer Working Group.
PMID- 9650156
TI - Menopause: when hormone replacement therapy is not an option. Part I.
AB - Although the perimenopausal period is often experienced as a positive life
transition, it is frequently accompanied by a variety of distressing physical and
emotional sequelae. Hormone replacement therapy (HRT) has been hailed as the
first-line treatment for many of these symptoms. A significant number of women,
however, are unable to take exogenous hormones because of absolute or relative
contraindications to therapy. Other women are unwilling to use this treatment for
a variety of reasons, including reluctance to use unnatural exogenous hormones
and fear of unknown risks of HRT. This two-part review discusses the physiology
of menopause and its related symptoms, as well as the risks and benefits of both
oral and non-oral routes of hormone administration. Self-help measures and
alternative therapeutic options are recommended for the treatment of menopausal
symptoms, which include vasomotor instability, urogenital atrophy, psychologic
disturbances, and risk of osteoporosis and cardiovascular disease.
PMID- 9650157
TI - Compromised bone density 11.4 years after diagnosis of anorexia nervosa.
AB - This investigation evaluated bone density in 36 premenopausal women (mean +/- SD
age = 29.5 +/- 8.4 years) an average of 11.4 years after diagnosis for anorexia
nervosa. Twenty-nine women were aged 20-45 years, and seven were aged 16-19
years. Body composition, age of menarche, length of amenorrhea, estrogen
exposure, and lumbar spine and proximal femur bone density were determined.
Average appendicular bone density for those > or = 20 years was found to meet
World Health Organization T score criteria for osteopenia: total femur T = -1.22
and femoral neck T = -1.33. The average total lumbar Z score for all 36
participants was -0.95, which was 90% of the mean for their age, and the mean Z
scores for adolescent subjects were within 91% of the mean for their age (Z =
0.84). Years of estrogen exposure were correlated with lumbar mineral content (r
= 0.50, p = 0.002). A modest but significant inverse relationship was observed
between length of amenorrhea and femoral and lumbar bone density. The total
proximal femur and trochanteric bone densities were best predicted, using
stepwise regression, by the number of years after diagnosis and years of
amenorrhea, respectively (R2 = 0.23, p = 0.02 and R2 = 0.21, p = 0.04). Lumbar
density was best predicted by years of amenorrhea and current percent of ideal
body weight (%IBW)(R2 = 0.25, p = 0.02). Length of amenorrhea, estrogen exposure,
and %IBW independently contribute to axial and appendicular bone density. Because
of risk for compromised bone density, women with a history of anorexia nervosa
should be followed longitudinally to maximize premenopausal bone replacement.
PMID- 9650158
TI - Impairment of autonomic function induced by posture change in postmenopausal
women.
AB - This study was designed to determine if there is a difference in autonomic
regulation induced by posture change between postmenopausal and young women. To
evaluate autonomic nervous system function, spectral analysis of heart rate
variability (HRV) was done in postmenopausal women (n = 13, 46-59 years of age),
age-matched men (n = 8, 45-55 years of age), and young women (n = 10, 20-37 years
of age) for 3-min periods of controlled frequency breathing (15 breaths/min) in
supine followed by sitting positions. In the supine position, the R-R interval
variation in older persons decreased significantly compared with that during the
follicular phase in young women. Furthermore, the high-frequency (HF) components
of HRV, which reflect only parasympathetic activity, were lower in older subjects
than in young women. Following a change of position from supine to sitting, the
HF component did not change significantly in the postmenopausal women or the men,
but the low/high frequency (LF/HF) component ratio, which reflects the balance of
autonomic nerve activities, increased significantly in the men. These results
suggest that cardiac parasympathetic tone may be reduced in older persons in
comparison with young women. Furthermore, arterial baroreflex control of
parasympathetic nerve activity caused by posture changes is impaired in the
postmenopausal women and aged-matched men. The baroreflex control of the
sympathetic component is maintained in the men but not in the postmenopausal
women. These differences might result in part from changes in the level of female
hormones.
PMID- 9650159
TI - Stress urinary incontinence in women: guidelines for surgical treatment.
PMID- 9650160
TI - Preventing HIV infection: the effects of community linkages, time, and money on
recruiting and retaining women in intervention groups.
AB - Few studies have addressed recruitment and retention of participants in
preventive interventions directed at human immunodeficiency virus (HIV), and
these generally have not focused on women. In this study, part of the Women in
Group Support (WINGS) project, we examine the experience of three sites in
recruiting 444 high-risk women for a small group intervention to reduce risky
sexual behavior. The intervention included six structured sessions, followed by a
continuing series of client-focused, drop-in sessions. Incentives for
participants included child care, food, and transportation tokens. Attendees at
each structured session also received a cash incentive of $10-$20. Forty-six
percent of the women were recruited from community sources, 35% from clinics, and
19% from drug programs. Across all recruitment sources, almost a third of the
women reported having had a sexually transmitted disease (STD) in the past year,
88%-94% reported a risky male partner (who, they believed, had sex with other
partners or with sex workers, was an injecting drug user, or was HIV positive),
and 10%-36% reported trading sex for money or drugs. During 18 months of
recruitment, each site averaged 34 screening interviews monthly to secure 8
eligible women a month who completed baseline interviews and reported for
randomization. The average number of paid sessions attended by participants was
five of six (83%). Average attendance at unpaid sessions was 1 of 12 (8%). Key
facilitators to recruitment and retention included linkages with community
agencies and monetary incentives. Our findings suggest that researchers and
community service providers need to explore alternative strategies to paying
women for attending group sessions (e.g., incorporating group interventions into
existing program requirements) and balance these against the costs and
recruitment effectiveness.
PMID- 9650161
TI - Women as caregivers.
PMID- 9650162
TI - Anxiety and depression. Diagnosis and treatment during pregnancy.
PMID- 9650163
TI - Specificity of neurobehavioral outcomes associated with prenatal alcohol
exposure.
PMID- 9650164
TI - National Institutes of Health Consensus Development Conference statement on
cervical cancer. April 1-3, 1996.
PMID- 9650165
TI - LiteratureWatch.
PMID- 9650166
TI - 1st Vitreoretinal Symposium. March 20th and 21st, 1998 in Frankfurt am Main.
PMID- 9650167
TI - Proposition: federally mandated imaging standards (e.g., MQSA) serve the best
interests of patients.
PMID- 9650168
TI - Preliminary study of a metal/a-Se-based portal detector.
AB - A feasibility study has been performed on metal/amorphous selenium detectors for
megavoltage portal imaging. The metal plates of the detectors were positioned
facing the incident 6 MV and Co-60 photon spectra. The detectors consist of
various thicknesses (0.15 mm, 0.30 mm, and 0.50 mm) of amorphous selenium (a-Se)
deposited on metal plates of varying thicknesses: aluminum (2.0 mm), copper (1.0
mm and 1.5 mm), stainless steel (0.9 mm), or glass (1.1 mm). The detectors were
charged prior to irradiation by corona methods, and the portal images were
subsequently digitized after irradiation with a noncontact electrostatic probe.
The sensitivity of the detectors to dose, electric field across the a-Se layer,
metal plate type and a-Se thickness, was studied. The electrostatic voltage
remaining on the a-Se layer was found, both theoretically and experimentally, to
exhibit a cubic relationship with respect to dose. An increase in electric field
increases the sensitivity (gradient of the a-Se surface voltage vs dose curve)
and dynamic range of the resultant image. An increase in a-Se thickness, however,
although also increasing the sensitivity, decreases the dynamic range. The metal
plate types and thicknesses within the range studied do not have a significant
effect on detector sensitivity. Image quality and contrast resolution of the
detector were evaluated with a contrast-detail phantom and compared to
commercially available film based and electronic portal imaging devices. Image
quality of the metal/a-Se detector as a function of dose was studied by
discharging the a-Se to various fractions of its initial charge, and as expected,
increases with dose due to a decrease in quantum noise. Contrast-detail images
obtained by metal/a-Se detectors are superior to those obtained at higher dose
levels by other commercial systems.
PMID- 9650169
TI - A simple algorithm for planar image registration in radiation therapy.
AB - A simple algorithm is presented for planar image registration and the method is
applied to the simulator and portal image registration for patient setup
verification in radiation therapy. Basically, the algorithm follows the concept
proposed by Balter et al. [Med. Phys. 19, 329-334 (1992)], which converts the
problem of open curve registration into matching a series of points along the
curves. Balter's algorithm consists of three steps: (1) to determine a common
starting point for each curve pair, (2) acquire two corresponding point sets
along each curve, and (3) obtain a global transform matrix by matching two point
sets. We integrate all three steps into one simple procedure which fits the
sampled points along the intended curve pair by taking the relative path length
shift as an independent fitting parameter. After being modified, the algorithm is
able to take the different magnification factors of images into account, and it
avoids curvature calculations. Numerical simulation as well as clinical and
phantom images have been utilized to test the accuracy of the algorithm. The
typical errors are less than 1 mm in translation and 1 degree in rotation. We
also made a comparison study with the chamfer method. The results of the two
methods agree to within 0.5 mm in translation and 0.5 degree in rotation.
PMID- 9650170
TI - Portal dose image (PDI) prediction for dosimetric treatment verification in
radiotherapy. I. An algorithm for open beams.
AB - A method is presented for calculation of transmission functions for high energy
photon beams through patients. These functions are being used in our clinic for
prediction of portal dose images (PDIs) which are compared with PDIs measured
with an electronic portal imaging device (EPID). The calculations are based on
the planning CT-scan of the patient and on the irradiation geometry as determined
in the treatment planning process. For each beam quality, the required input data
for the algorithm for transmission prediction are derived from a limited number
of measured beam data. The method has been tested for a PDI-plane at 160 cm from
the focus, in agreement with the fixed focus-to-detector distance of our
fluoroscopic EPIDs. For 6, 23 and 25 MV photon beams good agreement
(approximately 1%) has been found between calculated and measured transmissions
through anthropomorphic phantoms.
PMID- 9650171
TI - A pencil-beam photon dose algorithm for stereotactic radiosurgery using a
miniature multileaf collimator.
AB - A computer-controlled miniature multileaf collimator (MMLC) with 4 mm leaf width
and a maximum field size of 6 cm X 6 cm has been designed as a tertiary beam
shaping device for linac-based stereotactic radiosurgery. The purpose of this
study is to develop an accurate and efficient dose calculation model for use with
the MMLC. A pencil-beam based algorithm using a sum of three Gaussian kernels was
developed to model the off-axis ratio of MMLC fields. Because the kernel
integration over a rectangular field can be solved in closed form, dose to any
point from an arbitrary MMLC field can be calculated efficiently by summing dose
contribution from a set of rectangular apertures and transmission blocks that
model individual leaf openings or leaf transmissions. The model uses an effective
rectangular field and equivalent square method for determination of depth dose
and dose output. Results showed that the calculated percentage depth dose was
within 1% and output factor was within 1.5% of measured data. The parameters of
the pencil beam kernels were extracted by fitting measured off-axis profiles for
a few field sizes at a few depths. The accuracy of the calculated off-axis ratio
was tested by comparison with measured data for a number of MMLC fields. The
algorithm was shown to be accurate to within 1.5% or 1 mm for off-axis ratios.
The algorithm computes at a speed of 34,600 data points per second on a DEC Alpha
server model 2000/433 (Digital Equipment Corp., Maynard, MA), which is about 15
times faster than a Clarkson-type summation method.
PMID- 9650172
TI - Multiple scattering theory for total skin electron beam design.
AB - The purpose of this manuscript is to describe a method for designing a broad beam
of electrons suitable for total skin electron irradiation (TSEI). A theoretical
model of a TSEI beam from a linear accelerator with a dual scattering system has
been developed. The model uses Fermi-Eyges theory to predict the planar fluence
of the electron beam after it has passed through various materials between the
source and the treatment plane, which includes scattering foils, monitor chamber,
air, and a plastic diffusing plate. Unique to this model is its accounting for
removal of the tails of the electron beam profile as it passes through the
primary x-ray jaws. A method for calculating the planar fluence profile for an
obliquely incident beam is also described. Off-axis beam profiles and percentage
depth doses are measured with ion chambers, film, and thermoluminescent
dosimeters (TLD). The measured data show that the theoretical model can
accurately predict beam energy and planar fluence of the electron beam at normal
and oblique incidence. The agreement at oblique angles is not quite as good but
is sufficiently accurate to be of predictive value when deciding on the optimal
angles for the clinical TSEI beams. The advantage of our calculational approach
for designing a TSEI beam is that many different beam configurations can be
tested without having to perform time-consuming measurements. Suboptimal
configurations can be quickly dismissed, and the predicted optimal solution
should be very close to satisfying the clinical specifications.
PMID- 9650173
TI - Photon beam skin dose analyses for different clinical setups.
AB - A comprehensive set of data on skin dose for 8 MV and 18 MV photon beams from a
medical linear accelerator was measured using a parallel-plate chamber to
document the effect of field size, source-to-surface distance (SSD), off-axis
distance, acrylic block tray, wedge (external standard wedge), Lipowitz's metal
block, multileaf collimator (MLC), and dynamic wedge. The skin dose increased as
field size increased from 5 X 5 cm2 to 40 X 40 cm2 (6% to 38% for 8 MV and 5% to
44% for 18 MV beam). With the use of an acrylic block tray, the skin dose
increased for all field sizes (7% to 59% for 8 MV and 5% to 62% for 18 MV beam),
but the increase was minimal for small fields. The skin dose with a wedge showed
a much more complex trend. It was generally lower than the dose for an open
field, but higher in the case of large fields and higher degree wedges. When both
wedge and block tray were used, the tray was a major contributor to the skin dose
because some of the contaminant electrons from the wedge assembly were absorbed
by the block tray. Field-shaping blocks increased the skin dose, but,
interestingly, the block tray reduced the skin dose for small blocked fields
treated with a high-energy photon beam. The effect of an MLC on skin dose was
very similar to that of a Lipowitz's metal block, but its magnitude was less. The
skin dose was higher for dynamic wedge fields than it was for standard wedge
fields. As SSD decreased, the skin dose increased, and this effect was dominant
in larger field sizes. The SSD effect was enhanced in the presence of an acrylic
block tray. The skin dose off-axis was the same as at the central axis, or
smaller. A similar pattern of behavior of the skin dose is expected for photon
beams from other linear accelerators.
PMID- 9650174
TI - A patient-specific Monte Carlo dose-calculation method for photon beams.
AB - A patient-specific, CT-based, Monte Carlo dose-calculation method for photon
beams has been developed to correctly account for inhomogeneity in the patient.
The method employs the EGS4 system to sample the interaction of radiation in the
medium. CT images are used to describe the patient geometry and to determine the
density and atomic number in each voxel. The user code (MCPAT) provides the data
describing the incident beams, and performs geometry checking and energy scoring
in patient CT images. Several variance reduction techniques have been implemented
to improve the computation efficiency. The method was verified with measured data
and other calculations, both in homogeneous and inhomogeneous media. The method
was also applied to a lung treatment, where significant differences in dose
distributions, especially in the low-density region, were observed when compared
with the results using an equivalent pathlength method. Comparison of the DVHs
showed that the Monte Carlo calculated plan predicted an underdose of nearly 20%
to the target, while the maximum doses to the cord and the heart were increased
by 25% and 33%, respectively. These results suggested that the Monte Carlo method
may have an impact on treatment designs, and also that it can be used as a
benchmark to assess the accuracy of other dose calculation algorithms. The
computation time for the lung case employing five 15-MV wedged beams, with an
approximate field size of 13 X 13 cm and the dose grid size of 0.375 cm, was less
than 14 h on a 175-MHz computer with a standard deviation of 1.5% in the high
dose region.
PMID- 9650175
TI - Beam profiles for x-ray rotation therapy.
AB - Determining the beam configuration necessary to deliver a desired dose
distribution with rotation therapy is equivalent to solving an integral equation.
The equation has been solved analytically for a handful of dose distributions
having specific radial variation and either rotational or reflective angular
symmetry. In this work a numerical method for calculating beam profiles
appropriate for producing distributions having arbitrary radial variation and
angular symmetry of order l > or = 2 is presented. The accuracy of the technique
is demonstrated by comparison with one of the few dose distributions for which an
analytic solution exists, and the ability to produce both more general and
conformal distributions is also shown. The problems of negative intensity and
scatter are discussed.
PMID- 9650176
TI - Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry
of 10B neutron capture enhancement of fast neutron irradiations.
AB - Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use
thermal neutrons produced in depth of the tissues to generate neutron capture
reactions on 10B within tumor cells. The dose enhancement is correlated to the
10B concentration and to thermal neutron flux measured in the depth of the
tissues, and in this paper we demonstrate the feasibility of Monte Carlo
simulation to study the dosimetry of BNCE. The charged particle FLUKA code has
been used to calculate the primary neutron yield from the beryllium target, while
MCNP-4A has been used for the transport of these neutrons in the geometry of the
Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the
thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has
been calculated. The thermal neutron flux has been compared with experimental
results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD
700, respectively, doped with 6Li or 7Li). The theoretical results were in good
agreement with the experimental results: the thermal neutron flux was calculated
at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of
the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose
deposition the calculated and experimental curves have the same slope but
different shape: only the experimental curve shows a maximum at 2.27 cm depth
corresponding to the build-up. The difference is due to the Monte Carlo
simulation which does not follow the secondary particles. Finally, a dose
enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm
X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues.
It is anticipated that this calculation method may be used to improve BNCE of
fast neutron irradiations through collimation modifications.
PMID- 9650177
TI - A light localizer for use at large distances from a radiation source.
AB - In the superconducting cyclotron used for neutron therapy at Harper Hospital,
space limitations prevented the use of a simple conventional light localizing
system, employing a single mirror and a light source. The superconducting magnet
coil is close to the neutron producing target and the vacuum window separating
the acceleration chamber from atmospheric pressure is situated approximately 56
cm from this target. Therefore, the light localizing system must be designed to
incorporate lenses, mirrors, an optical fiber light pipe and adjustment motors,
in order to make the system compact enough to fit in the available space and to
allow easy access for adjustment and alignment. The design of the light
localizing system is explained in detail.
PMID- 9650178
TI - A practical target system for accelerator-based BNCT which may effectively double
the dose rate.
AB - A dose-limiting component of a proton accelerator-based source of epithermal
neutrons is the neutron production target. Possible targets are lithium,
producing high yield but having low melting point and thermal conductivity, and
beryllium, presenting less engineering problems but a much smaller neutron yield.
We propose that a hybrid Be-Li target would provide the best of both worlds, with
the upstream beryllium component producing neutrons and providing containment to
the lithium, and the downstream liquid lithium in turn producing further neutrons
as well as cooling the beryllium. The engineering considerations associated with
such a target system are within the range of current technology. Calculations
suggest a yield of such a practical target that is at least double that from pure
beryllium.
PMID- 9650179
TI - Microprocessor controlled limitation system for a stand-alone freely movable
treatment couch.
AB - Because of the capability of free movement in the treatment room, we recently
introduced a Hercules treatment couch on one of our linear accelerators. One of
the advantages of this couch is that it allows for a more flexible way of patient
setup and that it can be moved entirely out of the way to enable treatment with a
hospital bed. A disadvantage, however, is that the couch can hit a wall or a
cover of the accelerator accidentally. A limitation system has been developed to
protect both the table and the accelerator against such collisions.
PMID- 9650180
TI - Liquid ionization chambers for absorbed dose measurements in water at low dose
rates and intermediate photon energies.
AB - Two new liquid ionization chamber (LIC) designs, consisting of cylindrical and
plane-parallel configurations, are presented. They are designed to be suitable
for high-precision measurements of absorbed dose-to-water at dose rates and
photon energies typical for LDR intermediate photon energy brachytherapy sources.
The chambers have a sensitive liquid layer thickness of 1 mm and sensitive
volumes of 7 mm3 (plane-parallel) and 20 mm3 (cylindrical). The liquids used as
sensitive media in the chambers are either isooctane (C8H18), tetramethylsilane
(Si(CH3)4) or mixtures of these two liquids in the approximate proportions 2 to
1. A chamber filled with such a liquid mixture and with a polarizing voltage of
300 V, provides a volume sensitivity of about 10(-9)C Gy(-1) mm(-3) for absorbed
dose measurements in water in an x-ray radiation field with an effective photon
energy of 120 keV. In the interval 30 to 140 keV, the relative change in
sensitivity is less than +/- 2.5%. The leakage current of the chambers is low and
stable, which implies that absorbed dose measurements can be done with good
reproducibility at dose-rates as low as 50 microGy min-1 (sigma < 3%). The long
term calibration stability was tested for a set of five chambers over a period of
more than 1 year. No systematic change in their sensitivity could be observed.
The general recombination at a polarizing voltage of 300 V is less than 2% for
dose-rates up to about 100 mGy min-1. The temperature dependence at room
temperature is 0.5% per degree C. The response is almost independent of the
direction of the radiation for the plane-parallel LIC.
PMID- 9650181
TI - Determination of saturation charge and collection efficiency for ionization
chambers in continuous beams.
AB - The procedure recommended by radiation dosimetry protocols for determining the
collection efficiency f of an ionization chamber assumes the predominance of
general recombination and ignores other charge loss mechanisms such as initial
recombination and ionic diffusion. For continuous radiation beams, general
recombination theory predicts that f can be determined from a linear relationship
between 1/Q and 1/V2 in the near saturation region (f > 0.7), where Q is the
measured charge and V the applied chamber potential. Measurements with Farmer
type cylindrical ionization chambers exposed to cobalt-60 gamma rays reveal that
the assumed linear relationship between 1/Q and 1/V2 breaks down in the extreme
near-saturation region (f > 0.99) where Q increases with V at a rate exceeding
the predictions of general recombination theory. A comprehensive model is
developed to describe the saturation characteristics of ionization chambers. The
model accounts for dosimetric charge loss (initial recombination, ionic
diffusion, and general recombination) and nondosimetric charge multiplication in
an ionization chamber, and suggests that charge multiplication plays a
significant role under typical chamber operating conditions (300 V) used in
radiation dosimetry. Through exclusion of charge multiplication from the measured
chamber signal Q, the model predicts the breakdown of the 1/Q vs 1/V2
relationship and shows that the final approach to saturation is governed by
initial recombination and ionic diffusion which are characterized by a linear
relationship between 1/Q and 1/V. Collection efficiencies calculated with this
model differ by up to 0.4% from those determined through a rigorous application
of general recombination theory alone.
PMID- 9650182
TI - Influence of electron contamination on in vivo surface dosimetry for high-energy
photon beams.
AB - The influence of the electron contamination at in vivo dosimetry with diodes on
the patient surface has been investigated by introducing different accessories in
the beam path and by changing the field size and SSD. The results show a clear
correlation between the electron contamination at an effective measuring depth of
the diode and the signal from the patient diode. When the electron contamination
is taken into account the agreement between the diode values and the absorbed
dose is greatly improved. More accurate in vivo dosimetry with less error margins
is therefore possible if better predictions of the electron contamination in high
energy photon beams can be performed.
PMID- 9650183
TI - Texture analysis in radiographs: the influence of modulation transfer function
and noise on the discriminative ability of texture features.
AB - Tissue structures, represented by textures in radiographs, can be quantified
using texture analysis methods. Different texture analysis methods have been used
to discriminate between different aspects of various diseases in primarily x rays
of chest, bone, and breasts. However, most of these methods have not specifically
been developed for use on radiographs. Certain characteristics of the
radiographic process, e.g., noise and blurring, influence the visible texture. In
order for a texture analysis method to be able to discriminate between different
underlying textures, it should not be too sensitive for such processes as image
noise and blur. In this study, we investigated the sensitivity of four different
texture analysis methods for image noise and blur. First, a baseline measurement
was performed of the discriminative performance of the Spatial Gray-Level
Dependence method, the Fourier Power Spectrum, the Fractal Dimension, and the
Morphological Gradient Method on images, which were not affected by radiographic
noise and blur. Two types of images were used: fractal and Brodatz. Whereas the
Brodatz images represent very different textures, the differences between the
fractal images are more gradual. We assume that the behavior of the different
texture analysis methods on the fractal images is representative for their
performance on radiologic textures. On these types of images we simulated the
effect of four different noise levels and the effect of two different modulation
transfer functions, corresponding with different screenfilm combinations. The
influence on the discriminative performance of the four texture analysis methods
was evaluated. The influence of noise on the discriminative performance is, as
expected, dependent on the image type used; the discrimination of more gradually
different images, such as the fractal images, is already lowered for relatively
low noise levels. In contrast, when the images are more different, only high
noise levels decrease the discriminative performance. The discriminative power of
the Morphological Gradient Method is least affected by image blur. We conclude
that the discriminative performance of the Morphological Gradient Method is
superior to that of other methods in circumstances which mimic the conditions
prevailing in radiographs.
PMID- 9650184
TI - Classification of compressed breast shapes for the design of equalization filters
in x-ray mammography.
AB - We are developing an external filter method for equalizing the x-ray exposure in
mammography. Each filter is specially designed to match the shape of the
compressed breast border and to preferentially attenuate the x-ray beam in the
peripheral region of the breast. To be practical, this method should require the
use of only a limited number of custom built filters. It is hypothesized that
this would be possible if compressed breasts can be classified into a finite
number of shapes. A study was performed to determine the number of shapes. Based
on the parabolic appearance of the outer borders of compressed breasts in
mammograms, the borders were fit with the polynomial equations y = ax2 + bx3 and
y = ax2 + bx3 + cx4. The goodness-of-fit of these equations was compared. The a,b
and a,b,c coefficients were employed in a K-Means clustering procedure to
classify 470 CC-view and 484 MLO-view borders into 2-10 clusters. The mean
coefficients of the borders within a given cluster defined the "filter" shape,
and the individual borders were translated and rotated to best match that filter
shape. The average rms differences between the individual borders and the
"filter" were computed as were the standard deviations of those differences. The
optimally shifted and rotated borders were refit with the above polynomial
equations, and plotted for visual evaluation of clustering success. Both
polynomial fits were adequate with rms errors of about 2 mm for the 2-coefficient
equation, and about 1 mm for the 3-coefficient equation. Although the fits to the
original borders were superior for the 3-coefficient equation, the matches to the
"filter" borders determined by clustering were not significantly improved. A
variety of modified clustering methods were developed and utilized, but none
produced major improvements in clustering. Results indicate that 3 or 4 filter
shapes may be adequate for each mammographic projection (CC- and MLO-view). To
account for the wide variations in exposures observed at the peripheral regions
of breasts classified to be of a particular shape, it may be necessary to employ
different filters for thin, medium and thick breasts. Even with this added
requirement, it should be possible to use a small number of filters as desired.
PMID- 9650185
TI - Optimally weighted wavelet transform based on supervised training for detection
of microcalcifications in digital mammograms.
AB - We are developing a computer-aided diagnosis (CAD) scheme for detection of
clustered microcalcifications in digital mammograms. The use of an empirically
chosen wavelet and scale combination for detection of microcalcifications as an
initial step of the CAD scheme has been reported by us previously. In this study,
we developed a technique for optimizing the weights at individual scales in the
wavelet transform to improve the performance of our CAD scheme based on the
supervised learning method. In the learning process, an error function was
formulated to represent the difference between a desired output and the
reconstructed image obtained from weighted wavelet coefficients for a given
mammogram. The error function was then minimized by modifying the weights for
wavelet coefficients by means of a conjugate gradient algorithm. The Least
Asymmetric Daubechies' wavelets were optimized with 297 regions of interest
(ROIs) as a training set by a jackknife method. The performance of the optimally
weighted wavelets was evaluated by means of receiver-operating characteristic
(ROC) analysis by use of the above set of ROIs. The analysis yielded an average
area under the ROC curve of 0.92, which outperforms the difference-image
technique used in our existing CAD scheme, as well as the partial reconstruction
method used in our previous study.
PMID- 9650186
TI - Computer-aided diagnosis: automatic detection of malignant masses in digitized
mammograms.
AB - A computerized method to automatically detect malignant masses on digital
mammograms based on bilateral subtraction to identify asymmetries between left
and right breast images was developed. After the digitization, in order to align
left and right mammograms the breast border and nipple were automatically
detected. Images were corrected to avoid differences in brightness due to the
recording procedure. Left and right mammograms were subtracted and a threshold
was applied to obtain a binary image with the information of suspicious areas.
The suspicious regions or asymmetries were delimited by a region growing
algorithm. Size and eccentricity tests were used to eliminate false-positive
responses and texture features were extracted from suspicious regions to reject
normal tissue regions. The scheme, tested in 70 pairs of digital mammograms,
achieved a true-positive rate of 71% with an average number of 0.67 false
positives per image. Computerized detection was evaluated by using free-response
operating characteristic analysis (FROC). An area under the AFROC (A1) of 0.667
was obtained. Our results show that the scheme may be helpful to the radiologists
by serving as a second reader in mammographic screening. The low number of false
positives indicates that our scheme would not confuse the radiologist by
suggesting normal regions as suspicious.
PMID- 9650187
TI - Evaluation of imaging geometries calculated from biplane images.
AB - A technique is developed that will calculate accurate and reliable imaging
geometries and three-dimensional (3D) positions from biplane images of a
calibration phantom. The calculated data provided by our technique will
facilitate accurate 3D analysis in various clinical applications. Biplane images
of a Lucite cube containing lead beads 1 mm in diameter were acquired. After
identifying corresponding beads in both images and calculating their image
positions, the 3D positions of the beads relative to each focal spot were
determined. From these data, the transformation relating the 3D configurations
were calculated to give the imaging geometry relating the biplane views. The 3D
positions of objects were determined from the biplane images along with the
corresponding imaging geometries. In addition, methods are developed to evaluate
the quality of the calculated results on a case-by-case basis in the clinical
setting. Methods are presented for evaluating the reproducibility of the
calculated geometries and 3D positions, the accuracy of calculated object sizes,
and the effects of errors due to time jitter, variation in user-indication,
centering, and distortions on the calculated geometries and 3D reconstructions.
The precision of the translation vectors and rotation matrices of the calculated
geometries were within 1% and 1 degree, respectively, in phantom studies, with
estimated accuracies of approximately 0.5% and 0.4 degree, respectively, in
simulation studies. The precisions of the absolute 3D positions and orientations
of the calculated 3D reconstructions were approximately 2 mm and 0.5 degree,
respectively, in phantom studies, with estimated accuracies of approximately 1.5
mm and 0.4 degree, respectively, in simulation studies. This technique will
provide accurate and precise imaging geometries as well as 3D positions from
biplane images, thereby facilitating 3D analysis in various clinical
applications. We believe that the study presented here is unique in that it
represents the first steps toward understanding and evaluating the reliability of
these 3D calculations in the clinical situation.
PMID- 9650188
TI - Identification of lung regions in chest radiographs using Markov random field
modeling.
AB - The authors present an algorithm utilizing Markov random field modeling for
identifying lung regions in a digitized chest radiograph (DCR). Let x represent
the classifications of each pixel in a DCR as either lung or nonlung. We model x
as a realization of a spatially varying Markov random field. This model is
developed utilizing spatial and textural information extracted from samples of
lung and nonlung region-types in a training set of DCRs. With this model, the
technique of Iterated Conditional Modes is used to determine the optimal
classification of each pixel in a DCR. The algorithm's ability to identify lung
regions is evaluated on a testing set of DCRs. The algorithm performs well
yielding a sensitivity of 90.7% +/- 4.4%, a specificity of 97.2% +/- 2.0%, and an
accuracy of 94.8% +/- 1.6%. In an attempt to gain insight into the meaning and
level of the algorithm's performance numbers, the results are compared to those
of some easily implemented classification algorithms.
PMID- 9650189
TI - A comprehensive physical image quality evaluation of a selenium based digital x
ray imaging system for thorax radiography.
AB - A selenium based digital x-ray system dedicated to chest radiography has been
installed by the UK Department of Health's Medical Devices Agency at Leeds
General Infirmary, UK, to undergo a comprehensive evaluation, including the
physical image quality. The underlying characteristics which define the overall
image quality of a system are the following: sensitometric response, modulation
transfer function, and noise power spectrum. These have been measured objectively
on preprocessed digital data acquired under relevant radiographic conditions. The
image data is further processed prior to hard copy display. The displayed image
quality may only be measured subjectively; threshold contrast detail
detectability is such a measure which can be related to the objective measures of
image quality. The objective imaging characteristics suggest that Thoravision has
a significant advantage over conventional radiography imaging systems. However,
subjective measures have demonstrated that the image processing can have a
significant effect on the perceived image quality. Thoravision has the potential
to deliver a significantly improved image quality to clinicians with no increase
in radiation exposure to the patient, or image quality may be maintained with a
reduction in radiation exposure. Digital image processing is central to the
efficiency with which it achieves this.
PMID- 9650190
TI - Automated segmentation of anatomic regions in chest radiographs using an adaptive
sized hybrid neural network.
AB - The purposes of this research are to investigate the effectiveness of our novel
image features for segmentation of anatomic regions such as the lungs and the
mediastinum in chest radiographs and to develop an automatic computerized method
for image processing. A total of 85 screening chest radiographs from Johns
Hopkins University Hospital were digitized to 2 K by 2.5 K pixels with 12 bit
gray scale. To reduce the amount of information, the images were smoothed and
subsampled to 256 by 310 pixels with 8 bit. The determination approach consists
of classifying each pixel into two anatomic classes (lung and others) on the
basis of several image features: (1) relative pixel address (Rx, Ry) based on
lung edges extracted through image processing using profile, (2) density
normalized from lungs and mediastinum density, and (3) histogram equalized
entropy. The combinations of image features were evaluated using an adaptive
sized hybrid neural network consisting of an input, a hidden, and an output
layer. Fourteen images were used for the training of the neural network and the
remaining 71 images for testing. Using four features of relative address (Rx,
Ry), normalized density, and histogram equalized entropy, the neural networks
classified lungs at 92% accuracy against test images following the same rules as
for the training images.
PMID- 9650191
TI - A semianalytic model to investigate the potential applications of x-ray scatter
imaging.
AB - Although x-ray scatter is generally regarded as a nuisance that reduces
radiographic contrast (C) and the signal-to-noise ratio (SNR) in conventional
images, many technologies have been devised to extract useful information from
the scattered x rays. A systematic approach, however, for analyzing the potential
applications of x-ray scatter imaging has been lacking. Therefore, we have
formulated a simple but useful semianalytic model to investigate C and SNR in
scatter images. Our model considers the imaging of a target object against a
background material of the same dimensions when both are situated within a water
phantom. We have selected biological materials (liver, fat, bone, muscle, blood,
and brain matter) for which intermolecular form factors for coherent scattering
were available. Analytic relationships between C and SNR were derived, and
evaluated numerically as the target object thickness (0.01-40 mm) and photon
energy (10-200 keV) were systematically varied. The fundamental limits of scatter
imaging were assessed via calculations that assumed that all first-order scatter
exiting the phantom, over 4 pi steradians, formed the signal. Calculations for a
restricted detector solid angle were then performed. For the task of imaging
white brain matter versus blood in a 15 cm thick water phantom, the maximum SNR,
over all energies, for images based on the detection of all forward scatter
within the angular range 2 degrees-12 degrees is greater than that of primary
images for target object thicknesses < or = 23 mm. Use of the backscattered x
rays within the range 158 degrees-178 degrees to image objects 3 cm below the
surface of a 25 cm thick water phantom allows the liver to be distinguished from
fat with a SNR superior to that of primary imaging when the objects are < or = 22
mm thick. Our analysis confirms the usefulness of scattered x rays, and provides
simple methods for determining the regimes of medical interest in which x-ray
scatter imaging could outperform conventional imaging.
PMID- 9650192
TI - The effect on dose to computed tomography phantoms of varying the theoretical x
ray spectrum: a comparison of four diagnostic x-ray spectrum calculating codes.
AB - Theoretical x-ray spectra calculated by four different codes for the same tube
parameters are compared by calculating and measuring doses to computed tomography
(CT) body and head phantoms. The effect on the 120 kV spectrum, and hence on the
calculated dose, of varying the anode angle, tube voltage, and total filtration
of the x-ray tube is investigated. Codes used were those of Nowotny and Hofer
(XCOMP), Boone, Iles, and Tucker et al. The code based on the work of Tucker et
al. produced calculated doses noticeably lower than the other codes and compared
best to the measured value. The variation in calculated dose between the Tucker
code and the others is of the same order as the variation introduced by
uncertainties in total filtration of about 20%, in peak tube voltage of +/- 4 kV,
and in change of anode angle from 7 degrees to 13 degrees.
PMID- 9650193
TI - Panoramic radiology quality assessment.
AB - A procedure is proposed for performing noninvasive x-ray quality assessment tests
on panoramic radiology equipment. A simple cardboard tube jig eliminates relative
motion between the measurement system and the narrow, collimated x-ray beam.
Accurate measurements of beam HVL, x-ray exposure coefficient of variation and mA
linearity may be obtained. Use of the tube jig permits easy and routine
monitoring of these important x-ray parameters as well as consistency checks of
tube output. Film/screen contact also should be routinely checked in the clinic.
PMID- 9650194
TI - Exposure and dose in panoramic radiology.
AB - Panoramic radiology entrance skin exposure (ESE) was measured for a Siemens
Orthopantomograph 10 E using a thimble chamber and TLDs. Thimble chamber
measurements are shown to be inaccurate for the moving, narrow beam panoramic
scan geometry due to partial volume and partial charged-particle equilibrium
effects. For 75 KVp, 8 mA panoramic scans the TLD measured beam central ray ESE
on the scan central plane (patient midsagittal plane) was an approximately
constant 20 mR for the first 7.5 cm from the entrance slit. A theoretical model
of central plane ESE for a fixed rotation center agrees very well with the TLD
measurements and is consistent with all of the known ESE (and dose) properties
near rotation centers. Head phantom skin dose measurements demonstrate the
dependence of skin dose on exact equipment mode of use and patient anatomy.
Central plane, beam central ray ESE is judged to be a convenient, universal
measure of panoramic radiology radiation output.
PMID- 9650195
TI - Specific absorption rate ratio patterns of cylindrical ultrasound transducers for
breast tumors.
AB - The purpose of this paper is to examine the optimal driving frequency and to
configure the ultrasound energy deposition schema for a various size and location
of breast tissues when a portion or the entire cylindrical ultrasound transducer
is employed for breast hyperthermia treatments. This work employs a computer
simulation program based on an ideal ultrasound power deposition from a
cylindrical transducer. The ultrasound power within the breast is assumed to be
exponentially attenuated according to the penetration depth of the ultrasound
beam and a uniform absorption for the entire breast is also assumed. The
distribution of the specific absorption rate (SAR) ratio is employed to determine
the heating pattern of a set of given parameters. The control parameters
considered are the ultrasound frequency in the breast tissue, the active portion
of cylindrical transducer, and the shifting distance between the central axes of
the breast and the transducer. The effect of the breast size on the SAR ratio is
also considered. Simulation results demonstrate that the breast size, the
ultrasound frequency in breast tissue, the shifting distance, and the active
portion of the cylindrical transducer are the potential parameters for
influencing the distribution of the SAR ratio. High frequencies should be used
for the superficial heating treatments and the active portion of the transducer
can be changed to obtain a region with an appropriate SAR ratio to cover the
treatment region. Low frequencies are used for deep heating treatments and the
region of the high SAR ratio can be moved by shifting the transducer and its
pattern is varied with the transducer's active portion. The distribution of the
SAR ratio indicates the domain of treatable tumor size and tumor depth for a
given set of parameters (driving frequency, shifting distance and active portion
of the transducer, as well as breast diameter). Findings of this study can be
used to know whether or not the tumor is treatable as well as to select the
optimal driving frequency and the appropriate active portion of the cylindrical
transducer for a treatment, and hopefully to design an appropriate cylindrical
ultrasound heating system for breast tumors.
PMID- 9650196
TI - Measurement of small inter-scan fluctuations in voxel dimensions in magnetic
resonance images using registration.
AB - We present a method to estimate fluctuations in voxel dimensions in MR images. In
the proposed method images of a standard test object are acquired serially and
registered to an initial dataset. We present the results of experiments where
changes in voxel dimensions between 0.1% and 2% were prescribed and measured with
an accuracy of 0.02%. The method can be integrated as part of a standard MRI
Quality Assurance program and may also be useful to correct for inter-scan
variability introduced by fluctuations in gradient performance.
PMID- 9650197
TI - Estimating RBEs at clinical doses from microdosimetric spectra.
PMID- 9650198
TI - [Analysis of telomeric length in epithelial carcinoma of the ovary].
AB - BACKGROUND: As a consequence of the high cell division rate, telomeric repeat
reduction in human tumor cells, giving rise to genetic instability, has recently
been described. The aim of this study was to analyze by Southern blot telomeric
length alterations in a retrospective group of patients with ovarian epithelial
carcinoma. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated
from paraffin-embedded tissue of 16 patients with ovarian epithelial carcinoma.
Telomeric Restriction Fragments (TRF) were studied by Southern blot and
densitometric analysis. RESULTS: No telomere alterations were detected in 37.5%
of patients (6/16). Of the remaining ten, 5 were found to have telomere reduction
and five telomere elongation. No significant correlation was found between
clinicopathological variables, response to chemotherapy, survival rate or time to
progression, and telomere length alterations. CONCLUSIONS: In ovarian epithelial
carcinoma telomere elongation may be a marker of the presence of immortal cells
within the tumor, but telomere or the absence of telomeric alterations do not
rule out the presence of these cells. Although TRF analysis can be performed in
paraffin-embedded tissues, it is not the best indicator of telomerase activity
and thus of tumor aggressiveness in early stages of this carcinoma.
PMID- 9650199
TI - [Factors associated with an atherogenic lipid profile in premenopausal women
without clinical cardiovascular disease].
AB - BACKGROUND: To investigate different factors associated to a non desirable lipid
profile in premenopausal women without cardiovascular disease. To determine the
independent factors of lipid profile as a whole of the sample, for planning
preventive studies. PATIENTS AND METHODS: We study (March 1994 to June 1996)
premenopausal women with alcohol consumption less than 14 g/day and normal serum
level of glucose. Group I: women with a non desirable lipid profile (total
cholesterol [TCH, mg/dl]/high density lipoprotein cholesterol [HDL-C, mg/dl] > or
= 5). Group II: with a desirable lipid profile (TCH/HDL-C < 5). The following
factors were analyzed: age, body mass index (BMI), waist/hip ratio (W/H),
systolic blood pressure (SBP, mmHg), fasting plasma insulin (fpI, microU/ml),
cigarette smoke (CS) and presence of parents with history of non insulin
dependent diabetes mellitus (NIDDM) or hypertension. STATISTICAL METHODS: Mann
Whitney and Student statistics. Contingency-table analysis (chi 2 statistic).
Pearson correlation and multiple linear regression. RESULTS: We analyzed 126
women (age = 30 +/- 8.2; 95% CI, 29-32; TCH = 197 +/- 36; 95% CI, 190-203 mg/dl),
with 20 women (group I) and 106 (group II). Women from group I had higher values
of W/H (0.83 +/- 0.04 vs 0.78 +/- 0.06; p < 0.001), BMI (29.9 +/- 9 vs 24.6 +/-
4.9; p < 0.03), fpI (12.9 +/- 10.4 vs 7.8 +/- 3.5; p < 0.05), SBP (125.9 vs 117;
p < 0.02), as well as higher percentage of smokers (75 vs 40%; p < 0.01) and
parents with NIDDM (60 vs 26%; p < 0.01) or hypertension (60 vs 49%; NS). No
differences of age were detected (32 +/- 7.3 vs 30 +/- 8.3; NS). BMI (0.32; p <
0.01), W/H (0.50; p < 0.01), SBP (0.27; p < 0.01) and fpI (0.33; p < 0.01) were
positively correlated with TCH/HDL-C ratio (n = 126). In multiple regression
analysis (n = 126), W/H (regression coefficient = 6.1; 95% CI, 3.1-9.1), fpI
(regression coefficient = 0.045; 95% CI, 0.018-0.072) and CS (regression
coefficient = 0.5; 95% CI, 0.336-0.667) were the only independent predictors (p <
0.01) of the TCH/HDL-C ratio, controlling a 46% of the variance (R2 = 0.46).
CONCLUSIONS: Our data indicates that central obesity, hyperinsulinemia and
cigarette smoke are independently associated to a high risk cardiovascular lipid
profile in premenopausal women without cardiovascular disease. This study
suggests the importance of these factors in the management of early lipid control
in these women.
PMID- 9650200
TI - [Gallium-67 (Ga-67) scintigraphy in tuberculosis and Mycobacterium avium-M.
intracellulare infections in patients with HIV infections].
AB - BACKGROUND: Diagnosis of mycobacterioses in HIV infected patients is sometimes
difficult because of atypical findings. The aim of this study was to assess the
utility of gallium scintigraphy in diagnosis of AIDS related mycobacterioses in
patients with fever of unknown origin. PATIENTS AND METHODS: We retrospectively
reviewed the scans of 220 HIV(+) patients with fever (176 males [80%] and 44
females) who were evaluated with conventional diagnostic procedures at least of a
week before. RESULTS: Gallium scintigraphy was positive in 114 patients (51%) and
negative in 106 (49%). Mycobacteria were isolated in 83 patients (38%), 75 of
these patients (90%) had a positive scintigraphy (sensitivity 90%; specificity
71%). Positive predictive value was 66% and negative predictive value was 92%.
Mycobacterium avium-M. intracellulare (MAI) and M. tuberculosis were diagnosed in
22 (29%) and 53 (71%) HIV(+) patients, respectively. Seventy one (94%) of 75
patients with mycobacterioses had gallium uptake in at least two localizations.
CONCLUSIONS: 67Ga scintigraphy is very useful in HIV(+) patients with fever of
unknown origin. A negative gallium scintigraphy makes unlikely the diagnosis of
mycobacterioses.
PMID- 9650201
TI - [Treatment of lymphoma in the aged].
PMID- 9650202
TI - [The European Union begins its road to orphan drugs].
PMID- 9650203
TI - [Smoking and school children: context, opinions and behavior].
AB - BACKGROUND: This paper studies smoking epidemiology in school-age students.
MATERIAL AND METHODS: A cross-sectional survey of 8th grade students (13-14 years
old) in the schools of Barcelona (Catalonia, Spain) in 1987, 1992 and 1994.
RESULTS: The perception of smoking in the students environment has decreased. The
proportion of regular smokers decreases, from 12.6% in 1987 to 9.5% in 1994 (p <
0.05) (an annual decrease of 3.5%) although the proportion who experiment with
tobacco remains table. CONCLUSIONS: There is a decrease in the prevalence of
regular smoking in the school-age population (13-14 years-old) in Barcelona
(Spain).
PMID- 9650204
TI - [Quality of life of patients with bone marrow transplant].
PMID- 9650205
TI - [Pathogenic mechanisms in systemic vasculitis. New concepts].
PMID- 9650206
TI - [Polyglobulia in the Canadas del Teide? Preliminary results of a prospective
study].
PMID- 9650207
TI - [Disseminated Mycobacterium kansasii infection with skin involvement in a patient
with acquired immunodeficiency syndrome].
PMID- 9650208
TI - [Impact of consensus for control of cholesterolemia in Spain].
PMID- 9650209
TI - [Advice of the general practitioner and healthy life styles: is there an
alternative to passivity caused by technical and ethical difficulties?].
PMID- 9650210
TI - [Ambulatory versus stationary radiotherapy].
PMID- 9650211
TI - [Comparison of 51Cr-EDTA with 99m-Tc-DTPA slope clearance for estimation of
glomerular filtration rate using the one compartment model].
AB - AIM: Of this study is to determine the relationship between 51Cr-EDTA and 99mTc
DTPA slope clearance applying the "one-compartment model". METHODS: The "one
compartment model" was chosen to calculate and to compare the glomerular
filtration rates of 25 patients with normal and pathological creatinin values
after injection of 51Cr-EDTA and 99mTc-DTPA simultaneously. RESULTS: The two
clearance values correlated well (r = 0.996), and the 99mTc-DTPA clearance was
systematically higher (28%). The 99mTc-DTPA was calculated and compared after
taking three plasma samples. Taking two samples, only minor differences were seen
and the correlation was high (r = 0.992). CONCLUSION: The results of this study
encouraged us to adopt the use of 99mTc-DTPA instead of 51Cr-EDTA in determining
the glomerular filtration applying the "one-compartment model" in slope with two
plasma samples.
PMID- 9650212
TI - [Clinical relevance of I-123/I-131-MIBG scintigraphy in intestinal carcinoid
tumors].
AB - AIM: Of this retrospective study was to determine the value of MIBG-scintigraphy
in patients with intestinal carcinoids dependent on histological, clinical, and
biochemical parameters. METHODS: In 15 patients uptake in carcinoid tumors and
metastasis was correlated with location of the primary tumor, intra- and
extrahepatic tumor masses, histology, immunhistochemistry, neuroendocrinological
markers, and clinical symptoms. RESULTS: High uptake was to be seen almost only
in tumor masses of primary tumors located in the terminal ileum. There also was a
positive correlation with clinical symptoms for carcinoids and urinary 5-HIAA
level. No correlation between MIBG uptake and tumor masses, histology, and most
of the immunhistochemical and neuroendocrinological markers could be found.
CONCLUSION: There is a limited indication for MIBG-scintigraphy in follow up of
intestinal carcinoids. In patient with proven uptake MIBG scintigraphy is
suitable for long-term follow up and therapy monitoring.
PMID- 9650213
TI - [Kinetics of receptor-mediated radiotoxicity of 16alpha-[125I]-iodostradiol
3,17beta].
AB - AIM: The radiocytotoxic effects in estrogen receptor (ER) containing MCF-7 cells
of a mamma carcinoma were investigated following incubation with [125I]E ranging
from 1 h to 24 h. METHODS: The receptor status of the cells was confirmed by
immunohistochemical staining. The accumulation of [125I]E in MCF-7 cells was
tested in the presence and absence of radioinert E and [127I]E and in ER-negative
cells in comparison to ER-positive cells. The subcellular distribution was
investigated in 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity
was assessed in ER-positive and negative cells by a standard colony forming assay
after incubating with [125I]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and
24 h. RESULTS: A significant cytotoxicity was observed only when ER-rich MCF-7
cells were incubated with [125I]E alone. The maximal cytotoxic effect was a
reduction of survival fraction to 20-25%. This was achieved at radioactivity
concentrations > 37 kBq/ml. Maximal effect was seen after 8 h incubation,
extension of incubation time did not further increase toxicity. CONCLUSION: The
results suggest that the radioactivity was bound to ER. Through their nuclear
localization radioestrogens tagged with radionuclides emitting very low energy
electrons (Auger electrons) bear potential for therapy by ER-mediated deposition
of lethal doses of ionizing radiation to single cells without affecting
neighbouring cells. But, instead of 125I the shorter-living 123I shall be used
for labelling because the deciding radiation effectes occur within the first 8 h.
PMID- 9650214
TI - Adrenocortical scintigraphy with 131I-6-beta-iodomethyl-norcholesterol (NP 59) in
bilateral adrenocortical carcinoma.
AB - A case of a 49-year-old man suffering from bilateral adrenocortical carcinoma
with local and secondary rapid progression is reported. The results of
adrenocortical scintigraphy (NP 59) and histological findings allowed the
diagnosis. This case report and a literature review showed the importance of
using adrenocortical scintigraphy as a complementary imaging procedure of CT or
MR images.
PMID- 9650215
TI - [Septal myocardial perfusion in complete left bundle branch block: case report
and review of the literature].
AB - Myocardial scintigraphy was performed three times in a 55-year-old woman with
left bundle branch block (LBBB). A significant LAD stenosis had been excluded by
coronary angiography. The first scintigraphy was performed with Tc-99m sestamibi
after submaximal bicycle exercise and revealed a septal perfusion deficit. This
deficit could not be reproduced in the following examinations after
pharmacological stress testing with dipyridamole using both Tl-201 and Tc-99m
sestamibi. Perfusion at rest assessed with Tl-201 was normal in all studies. It
is concluded that pharmacological stress testing with dipyridamole is to be
preferred in patients with LBBB. With respect to the accuracy of myocardial
perfusion imaging the choice of the radiopharmaceutical plays a less important
role.
PMID- 9650216
TI - [Scintigraphic assessment of function in renal dystopia].
AB - In patients with renal dystopia radionuclide urography in commonly used technique
may yield inaccurate results concerning split renal function. In a case of
unilateral pelvic kidney a simple strategy to avoid this methodical error is
demonstrated.
PMID- 9650218
TI - [Pathogenetic differentiation of the bone superscan using bone marrow
scintigraphy].
AB - The case of a 54 year old patient suffering from a prostatic carcinoma is
presented. At the time of diagnosis multiple bone metastases were detected by
bone scintigraphy. An initial improvement was observed following antiandrogenic
therapy. After three years the patient presented with increasing bone pain, which
was most prominent in the knee joints. A "superscan" was found in bone
scintigraphy with an unusually high uptake in the peripheral skeleton. Bone
marrow scinitgraphy showed a nearly complete metastatic displacement of central
bone marrow and a peripheral marrow extension as explanation for the bone scan
findings.
PMID- 9650217
TI - Pulmonary tumor microembolism.
AB - Pulmonary tumor embolism is an often missed antemortem diagnosis in patients with
cancer and respiratory failure. Although rare, this complication is an important
cause of additional morbidity. Referred for radionuclide pulmonary perfusion and
ventilation scintigraphy, a typical pattern of multiple subsegmental peripheral
defects on perfusion lung scanning without matching ventilation defects,
suggesting a high probability of pulmonary thromboembolism, often leads to false
conclusions. We present a case of bilateral multiple subsegmental mismatched
defects in lung ventilation perfusion scintigraphy, where autopsy confirmed the
diagnosis of pulmonary tumor embolism, secondary to an undifferentiated ductal
type adenocarcinoma of the pancreas. Pulmonary tumor embolism is an entity to
keep in mind in patients treated for carcinoma presenting with (sub) acute
dyspnea.
PMID- 9650219
TI - Remodelling: historical perspectives and definition of terms.
AB - The changes that occur in both the structure and geometry of blood vessels in
pathological conditions has been termed remodelling. The importance of the
changes in geometry have only been recently widely appreciated, although
geometric remodelling has been recognized for more than 30 years. Geometric
remodelling can be favourable, as occurs with compensatory enlargement, or
unfavourable, as with constriction. Vascular remodelling is recognized to occur
in a variety of pathological conditions, including atherosclerosis, hypertension,
arterio-venous grafts, and following restenosis. A better understanding of the
pathophysiology should permit development of new therapeutic strategies to treat
these conditions.
PMID- 9650220
TI - Arterial remodelling by atherosclerosis.
AB - Until recently, plaque formation was considered to be the only determinant of
atherosclerotic luminal narrowing. Recent post-mortem and intravascular
ultrasound studies, however, revealed that arterial remodelling is another
important determinant of luminal narrowing in de novo atherosclerosis. The change
in total arterial circumference relative to a reference cross-section ranges from
excessive enlargement with an actual increase in lumen to arterial shrinkage
contributing to lumen narrowing. The mechanisms responsible for this spectrum of
remodelling are unknown, but their identification will be important for the
potential development of therapeutic strategies to promote favourable
remodelling.
PMID- 9650221
TI - Remodelling and restenosis: insights from animal studies.
AB - Animal studies have been instrumental in elucidating the process of remodelling
and its contribution to restenosis relative to neointimal formation following
angioplasty. The majority of studies have utilized rabbit, porcine and nonhuman
primate models of vascular injury. Despite the use of different experimental
models, different forms of vascular injury, different methods of analysis and
different definitions of arterial remodelling, all animal studies, with rare
exceptions, have demonstrated the importance of remodelling in the maintenance of
vascular patency in both atherogenesis and in restenosis following angioplasty.
The finding that remodelling in the non-human primate is most comparable to that
that occurs in man suggests that there may be a genetic predisposition to the
balance of neointimal formation and arterial remodelling following vascular
injury.
PMID- 9650222
TI - Remodelling and restenosis: intravascular ultrasound studies.
AB - Remodelling, defined as a change in total vessel area, was demonstrated to be
another important mechanism of restenosis after coronary angioplasty in a study
utilizing intravascular ultrasound. In this study, remodelling was also
demonstrated to be bidirectional (constrictive modelling and adaptive
remodelling). A recent serial intravascular ultrasound study revealed that time
course of remodelling after coronary angioplasty was typically biphasic; early
(post-procedure-1 month) adaptive remodelling and late (1 month-6 months)
constrictive remodelling. Remodelling after coronary angioplasty should be
regarded not only as a cause of restenosis but also as a mechanism maintaining
patency.
PMID- 9650223
TI - The role of the extracellular matrix in arterial remodelling.
AB - The extracellular matrix is now recognized as a biologically active and dynamic
composition of structural, adhesive, and counteradhesive fibrous proteins
embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans.
The ability of resident cells to detect small differences in the specific
combination, concentration and distribution of matrix components suggests that
perturbation of the homeostatic matrix can lead to remodelling following
angioplasty. Recent studies reviewed herein have focused on how alterations of
the relative composition of matrix components ultimately leads to changes in cell
growth, behaviour and differentiation, all of which can significantly contribute
to remodelling of the vascular wall following injury. These cell-matrix
interactions may provide novel therapeutic targets in the prevention of
unfavourable remodelling that leads to restenosis.
PMID- 9650224
TI - Remodelling: therapeutic opportunities.
AB - Restenosis after angioplasty has been recently attributed to a lack of
compensatory enlargement and/or chronic constrictive remodelling, rather than
neointimal growth. Also, restenosis occurring after stent has been clearly
related to neointimal growth. This clarification has dramatically helped in
designing strategies targeted against the appropriate mechanisms. The mechanism
of stent-related restenosis has been the most studied and several
antiproliferative agents including gene therapy and radioactive stents have been
successfully tested. Constrictive remodelling has been identified more recently
and its pathophysiological mechanism remains poorly understood. Control of
extracellular matrix metabolism might be an important pathway. Moreover,
detection of the arteries that will 'enlarge' should avoid any preventive
strategy including systematic stenting.
PMID- 9650225
TI - The physician's moral obligations to the pregnant woman, the fetus, and the
child.
AB - The moral obligations and ethical duties of health care professionals responsible
for the care of a pregnant woman, a fetus, and a child are complex and evolve
with gestation and birth. Well-intentioned physicians and others concerned with
the interests of pregnant women and their fetuses may disagree about the moral
status of the fetus and ethical duties owed to both the woman and fetus. This
article lays out a framework for thinking about these issues from several
perspectives.
PMID- 9650226
TI - Ethical issues in reproductive genetics.
AB - Because of technological developments in reproductive genetics, couples now have
many options not available a decade ago. Some developments are controversial and
deeply divide our society. This article examines some of these issues and
establishes guidelines of approach.
PMID- 9650227
TI - Ethical dilemmas in the delivery room.
AB - The decision to withhold or withdraw life support in the neonatal intensive care
unit (NICU) is common but is never routine. Often, moral demands make such
decisions difficult and emotionally exhausting. But, what is perhaps more
challenging from the moral point of view is the transition from the delivery room
to the NICU. A satisfactory analysis of the moral issues of delivery room
practices must include a discussion of quality of life, the best interest of the
infant, the best interests of the family members, and futile treatment. Although
these topics are relevant in any discussion of the moral justification of the
omission, withdrawal, or use of treatment for patients, they are especially
telling when entertained in the context of the transition of the fetus to a
newborn. This article uses these four topics as a moral compass for certain
decisions made in the delivery room.
PMID- 9650228
TI - Ethical issues in the care of extremely low birth weight infants.
AB - This article examines the difficulties in making decisions about the medical
treatment of infants who have uncertain viability because of extremely low birth
weight. The advantages and disadvantages of three systematic approaches are
reviewed. An approach called "provisional intensive care for all" may offer the
most benefit and cause the least harm. With this approach, all liveborn infants
would be presumed viable and would receive intensive care, at least initially.
After further assessment of the infant, the parents would be informed as fully as
possible about the possible outcome of continuing intensive care. The treating
physicians would offer the parents the options of continuing intensive care or
withdrawing it and providing basic care. Although the physicians would provide
recommendations based on their best medical judgment, they would be prepared to
support and carry out the parents' decision.
PMID- 9650229
TI - Futility considerations in the neonatal intensive care unit.
AB - The purpose of this article is to summarize and comment on the history of medical
decision making in the neonatal intensive care nursery, emphasizing
considerations of futility. Several epochs will be described, with shifting roles
of health care providers, the infant's family, and proxies for society at large.
Futility has been an issue in the intensive care of newborn infants throughout
the last 35 years. Long before the Baby Doe regulations and the formation of
ethics committees, neonatologists tried to determine which care measures were
indicated. Given the frequency of severe malformations, birth asphyxia, and
extreme prematurity, it has been a common event for the responsible physician to
ask himself: will this treatment be beneficial or merely futile? As the
therapeutic armamentarium became more powerful and complex, the choices from
among a possible array of interventions became increasingly difficult. The
autonomy of parents as decision makers was increasingly affirmed. In the 1980s,
the federal government, the courts, and frequent malpractice suits set boundaries
on medical decision making. In the 1990s, third party payors became increasingly
assertive in limiting resource expenditure. These legal and societal mandates are
frequently at variance with one another. Thus the issue of medical futility, as
it applies to neonates in the United States, must be considered unresolved.
PMID- 9650230
TI - Ethical dilemmas in medical innovation and research: distinguishing
experimentation from practice.
AB - The words research and experimentation continue to have the power to evoke fear
in potential subjects. But much of standard practice, particularly in critical
care settings, involves interventions of unknown efficacy and safety. Innovation
also abounds in practice settings, typically unchecked by prospective or
retrospective review. Historical attention has focused on the conflict of
interest of the physician/investigator, but contemporary safeguards have reduced
the risks of research and increased the likelihood that the patient/subject will
have the opportunity to make an informed choice. Innovation and untested
interventions in practice, in contrast, are often unknown to the patient and lack
institutional safeguards. Some common cliches that suggest that research is more
to be feared than standard practice will be examined, leading to the following
conclusions: defining an intervention as experimental may be less important in
ethical terms than the quality of prospective and retrospective review and the
standards for informed consent, and the concerns that led to regulation of
research should now be directed toward unproven interventions and innovation in
the practice setting.
PMID- 9650231
TI - Reproductive health under managed care: expanding provider obligations.
AB - The discussion of ethical issues in managed care can be focused on two general
areas. The first of these is the impact of the shift toward managed care on the
fiduciary relationship between health care professional and patient, including
the issue of trust, the potential for conflict of interest, and the impact of
cost-saving strategies on the clinician's ability to address a patient's health
care needs. The second is the attention to justice that managed care demands.
Health care professionals must take issues in both areas into account, attempting
to balance obligations to individual patients with obligations to patients
collectively. Strategies for doing so are discussed.
PMID- 9650232
TI - Guidance on the use of PrP genotyping as an aid to the control of clinical
scrapie. Scrapie Information Group.
PMID- 9650233
TI - Cataracts in farmed Atlantic salmon (Salmo salar) in Ireland, Norway and Scotland
from 1995 to 1997.
AB - From 1995 to 1997 cataracts were observed in Atlantic salmon (Salmo salar) in
Ireland, Norway and Scotland at around the time of smoltification (when
freshwater fish become adapted to the hypertonic seawater) in both fresh- and
seawater fish. Over 38,000 fish were screened for the presence of cataracts.
Posterior cortical cataracts were the earliest and most consistent change,
followed by perinuclear, equatorial and anterior cortical cataracts. On
histological examination vacuolation of the lens fibres was consistently present
in the posterior cortex. The pattern of the outbreak suggested that a nutritional
factor was involved although the variable incidence and severity of the condition
indicated that a number of modifying factors may have been involved in the
expression of the condition.
PMID- 9650234
TI - Clinical efficacy and safety of propofol or ketamine anaesthesia in dogs
premedicated with medetomidine.
AB - Combinations of medetomidine with either propofol or ketamine were compared for
the sedation and induction of anaesthesia in dogs undergoing a variety of
surgical (60 per cent) and non-surgical (40 per cent) procedures. Eighty-four
dogs were used at four sites. Medetomidine was administered intramuscularly at a
dose of 1000 micrograms/m2 body surface area 10 to 15 minutes before the
induction of anaesthesia by the administration of propofol (n = 44) or ketamine
(n = 40) dosed to effect. The dogs became sedated by medetomidine after a mean
(sd) time of 6.7 (5.4) minutes, and their heart rates and respiration rates
decreased. Sixteen of the dogs suffered an adverse effect, 13 of them vomited.
Anaesthesia was induced by the intravenous administration of propofol (2.1 [0.7]
mg/kg) or ketamine (3.7 [1.9] mg/kg), and further doses of the anaesthetic were
given, depending on the length of the operation, once in 17 per cent, twice in 11
per cent and three or more times in 24 per cent of the cases. The heart rate of
the dogs anaesthetised with ketamine was significantly higher than that of the
dogs anaesthetised with propofol, but there were no other significant
physiological differences. There were 11 adverse side-effects in the ketamine
group compared with five in the propofol group and they were generally more
severe. The quality of the recovery from anaesthesia was considered to be smooth
in 89 per cent of the propofol group but in only 63 per cent of the ketamine
group.
PMID- 9650235
TI - Use of metronidazole in equine acute idiopathic toxaemic colitis.
AB - Sixteen cases of acute idiopathic toxaemic colitis developed in a veterinary
hospital over a period of three years. Before the onset of colitis, 15 horses had
received antibiotics, 11 had undergone general anaesthesia and various surgical
procedures, and 10 had been treated with non-steroidal anti-inflammatory drugs.
The horses had acute onset, profuse watery diarrhoea, profound depression, mild
to moderate abdominal pain, reduced intestinal borborygmi, tachycardia,
dehydration and endotoxic shock. Leucopenia, neutropenia and pyrexia were common
early indicators of impending colitis. Metronidazole appeared to be an effective
treatment; eight horses treated with metronidazole survived whereas five of seven
horses that received other treatments, but no metronidazole, died or had to be
euthanased. The aetiology of the colitis could not be determined, but the
clinicopathological features resembled those of colitis attributed to an
intestinal overgrowth of Clostridium perfringens type A. No Salmonella species
were isolated from 52 samples of faeces, colonic contents and colonic mucosa
which were collected from the horses antemortem and postmortem.
PMID- 9650236
TI - Use of disease models in the development and evaluation of therapeutic agents.
AB - A key part of the regulatory review of new therapeutic agents depends on a clear
demonstration of their efficacy. There can be difficulties when the evaluations
of efficacy depend only on in vitro studies, such as minimum inhibitory
concentrations (MICs), and clinical field trials. The MIC data often correlate
poorly with in vivo results, and field trials can suffer from the
unpredictability of disease outbreaks and from differences in the severity of
outbreaks at different sites. This paper discusses the use of experimentally
induced diseases as a means of bridging the gap between the in vitro data and the
results of field trials.
PMID- 9650237
TI - Paralytic phycotoxins in monk seal mass mortality.
PMID- 9650238
TI - Pancreatic necrosis in a llama.
PMID- 9650239
TI - Detection of strangles carriers.
PMID- 9650240
TI - Surgical treatment of oral stereotypies in horses.
PMID- 9650241
TI - History of trauma and attempted suicide among women in a primary care setting.
AB - The results of past research have demonstrated apparent links between suicidality
and a history of sexual abuse or physical abuse. However, the relative predictive
power of such abuse histories in explaining sucidality remains unknown, as does
the potential relationship between sucidality and emotional abuse, physical
neglect, and witnessing violence. In the current study, 151 women who presented
for nonemergent medical care indicated whether they had experienced each of five
types of abuse and whether they had ever attempted suicide. Similar to past
research, increased rates of having attempted suicide were evident among women
who had been sexually or physically abused. Rates of past suicide attempts were
also higher among those who had experienced emotional abuse or had witnessed
violence. However, many women indicated having experienced multiple forms of
trauma. In a multivariate analysis, only sexual abuse and physical abuse were
uniquely predictive of having attempted suicide. Results are discussed with
regard to the potential importance of bodily intrusiveness during abuse as most
predictive of subsequent suicidality.
PMID- 9650242
TI - Correlates of sexual assault in Mexican American and white non-Hispanic
adolescent males.
AB - Psychosocial and emotional characteristics were assessed in a nonclinical sample
of 1,385 adolescent Mexican American and White non-Hispanic males. Fifty-four
males who reported being sexually assaulted one or more times were compared to
1,331 males who reported no history of sexual assault. Sexually assaulted male
victims were more emotionally distressed, socially isolated, deviant (e.g., lying
& stealing), likely to affiliate with deviant peers, and to come from homes in
which there was parental substance use, than males who did not report sexual
assault. Significant differences were not found between Mexican American and
White non-Hispanic assault victims. Implications of these findings are discussed.
PMID- 9650243
TI - Immigrants and the criminal justice system: an exploratory study.
AB - Experts have argued that there are significant barriers to recent immigrants' use
of the criminal justice system. This exploratory study, using convenience
samples, is among the first to look empirically at the experiences of recent
immigrant victims with the criminal justice system in the United States. Contrary
to expectations, we found that immigrants reported relatively few problems unique
to foreign-born persons in dealing with the police and the courts, and that their
satisfaction with the justice system was comparable to levels reported in studies
of native-born victims. The results suggest that although recent immigrants'
expectations of the criminal justice system may be different from those of native
born, the experiences of immigrant victims and their satisfaction with the
justice system are similar in many respects to those of native-born victims.
PMID- 9650244
TI - Close relationships of violent and nonviolent African American delinquents.
AB - One hundred and one incarcerated African American adolescent delinquents, 51
violent and 50 nonviolent were contrasted on background variables and measures of
close relationships. Violent delinquents were found to be older, have a greater
number of arrests, lower reading achievement scores, and were more likely to have
a criminal parent in the home. Violent, as compared with nonviolent delinquent,
showed differences in close relationships. Violent delinquents were more likely
to perceive their mothers as showing more rejection/undifferentiated behavior and
their attachments, mainly to hetero-sexual partners, were more anxious. The
results were interpreted in terms of both quantitative and qualitative
distinctions between violent and nonviolent delinquents, with violent delinquents
showing greater impairment.
PMID- 9650245
TI - Coercive sexual strategies.
AB - This study examines the use of coercive sexual strategies by men and the outcomes
of these behaviour for women. Using a sample of 541 college undergraduates, data
were gathered from men on their use of three types of coercive sexual strategies
and from women on their experiences with these same forms of behaviors. For
women, there is a positive association between being sexually active, having
sexually permissive attitudes, drinking alcohol and being a victim of certain
types of sexual coercive strategies. For men, sexually permissive attitudes and
attitudes toward rape are found to be significant predictors of their use of
verbal coercion. Furthermore, being a fraternity member is associated with the
use of verbal coercion and physical force and being a sorority member is
associated with being a victim of alcohol/drug coercion and physical force.
Reports from both men and women give a more comprehensive interpretation of the
specific mechanisms through which different coercive strategies are played out.
PMID- 9650246
TI - Relationships between experiences of parental violence during childhood and
women's self-esteem.
AB - The interrelationships between experience of parental verbal aggression and
physical violence during childhood and the development of low self-esteem during
adulthood were explored separately for the father-daughter and mother-daughter
relationships. Data were collected from 472 women between the ages of 18 and 45
during in-depth interviews drawn from five sources: outpatient alcoholism
treatment, DWI (Driving While Intoxicated) education programs, shelter for
battered women, outpatient mental health treatment, and randomly from the
community. Control variables included respondents' alcohol problems and help
seeking behavior, parental alcohol problems, number of changes in childhood
family (e.g., divorce), and respondents' race and social class. Controlling for
these variables, experiences of father-to-daughter verbal aggression, moderate
violence, and severe violence were found related to lower self-esteem in
adulthood for women. Conversely, controlling for these variables, experiences of
mother-to-daughter verbal aggression, moderate violence, and severe violence were
not found related to lower self-esteem in adulthood for women.
PMID- 9650247
TI - Follow-up of rapists treated in a forensic psychiatric hospital.
AB - Current research examining the effectiveness of sex offender treatment is
encouraging. Despite this optimism, research focusing on men who sexually assault
adult women is less optimistic. This study examines the preliminary results of 74
rapists admitted into the Phoenix program, a voluntary sex offender treatment
program in a forensic psychiatric hospital. Patients were categorized according
to whether they completed treatment or not. Treated rapists (n = 36) reoffended
at a substantially lower rate than untreated rapists who were assessed but not
treated (n = 38). Statistically significant differences in reoffense rates were
found for violent, nonsexual offenses as well as nonviolent, nonsexual offenses.
Although nearly twice as many treatment noncompleters reoffended sexually, the
difference between the two groups was not statistically significant. Mean follow
up time was well over four years for both groups. The implications of these
findings are discussed.
PMID- 9650248
TI - Degradation of dioxin-like compounds by microorganisms.
AB - Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF;
PCDD/F, dioxins) have not been commercially produced in bulk amounts, as were
polychlorinated biphenyls and other haloaromatic organics. Within the past two
decades a lot of information has accumulated on the biodegradation of PCDD/F and
other dioxin-like compounds because of their toxicity and because of significant
environmental concern about many congeners of this class of chemicals. PCDD/F are
subjected to reductive dehalogenations leading to less halogenated congeners,
which can be attacked efficiently by fungal and bacterial oxidases and
dioxygenases. In several cases these compounds can be utilized as carbon and
energy sources. Pathways for their enzymatic degradation and the organisation of
the corresponding degradative genes have been elucidated. Consequently,
biotechnological applications will exploit the degradative potential of such
microorganisms for bioremediation of contaminated sites.
PMID- 9650249
TI - Ethanol production using nuclear petite yeast mutants.
AB - Two respiratory-deficient nuclear petites, FY23 delta pet191 and FY23 delta
cox5a, of the yeast Saccharomyces cerevisiae were generated using polymerase
chain-reaction-mediated gene disruption, and their respective ethanol tolerance
and productivity assessed and compared to those of the parental grande, FY23WT,
and a mitochondrial petite, FY23 rho(0). Batch culture studies demonstrated that
the parental strain was the most tolerant to exogenously added ethanol with an
inhibition constant, Ki, of 2.3% (w/v) and a specific rate of ethanol production,
qp, of 0.90 g ethanol g dry cells-1 h-1. FY23 rho(0) was the most sensitive to
ethanol, exhibiting a Ki of 1.71% (w/v) and qp of 0.87 ethanol g dry cells-1 h-1.
Analyses of the ethanol tolerance of the nuclear petites demonstrate that
functional mitochondria are essential for maintaining tolerance to the toxin with
the 100% respiratory-deficient nuclear petite, FY23 delta pet191, having a Ki of
2.14% (w/v) and the 85% respiratory-deficient FY23 delta cox5a, having a Ki of
1.94% (w/v). The retention of ethanol tolerance in the nuclear petites as
compared to that of FY23 rho(0) is mirrored by the ethanol productivities of
these nuclear mutants, being respectively 43% and 30% higher than that of the
respiratory-sufficient parent strain. This demonstrates that, because of their
respiratory deficiency, the nuclear petites are not subject to the Pasteur effect
and so exhibit higher rates of fermentation.
PMID- 9650250
TI - Use of azo dye ligand chromatography for the partial purification of a novel
extracellular peroxidase from Streptomyces viridosporus T7A.
AB - Crude peroxidase preparations from the lignocellulose-degrading actinomycete,
Streptomyces viridosporus T7A, were shown to decolorize several azo dye isomers
and showed a correlation of dye structure to degradability similar to that shown
by fungal Mn-peroxidase, an enzyme not previously described in actinomycetes.
Addition of the heme-peroxidase inhibitor KCN did not significantly change the
ability of the T7A enzyme(s) to decompose the dyes. These results suggest that
T7A may produce an Mn- or other peroxidase with similar substrate specificity to
Mn-peroxidase. Affinity chromatography using immobilized azo dye isomers was used
for purifying peroxidases from T7A. A significantly purified peroxidase
preparation was obtained irrespective of the azo dye used. In comparison,
concanavalin A lectin affinity chromatography showed very poor binding and
resolution for T7A peroxidases. Azo dye affinity purification gave preparations
sufficiently purified to allow amino acid microsequencing for two of the bound
proteins. N-terminal amino acid sequences were found to share significant
homology with a fungal Mn-peroxidase and actinomycete cellulases.
PMID- 9650251
TI - Recombinant bioprocess optimization for heterologous protein production using two
stage, cyclic fed-batch culture.
AB - A two-stage, cyclic fed-batch bioprocess was designed, and its performance
evaluated to improve rice alpha-amylase productivity by the yeast Yarrowia
lipolytica SMY2 (MatA, ade1, ura3, xpr2), ATCC 201847, containing a replicative
plasmid coding for a rice alpha-amlyase. Transcription of the recombinant gene is
controlled by the XPR2 promoter. The first stage (or growth stage) was operated
in the fed-batch mode, and the growth medium, designed to maintain a constant
high cell density (i.e., 60 g/l), was fed according to a predetermined and
preprogrammed optimal feed rate which, in turn, maintained the specific cell
growth rate at an optimal value (i.e., 0.1 h-1). Typically, when the volume in
the first stage reached a preset value, a portion of culture broth (i.e., 55%)
was transferred to the second stage (or production stage). The remaining cells in
the growth stage were then fed with fresh growth medium according to the
bioprocess control strategy developed, while induction of alpha-amylase
expression and its production was taking place in the second stage. The second
stage was also operated in the fed-batch mode, and the production medium designed
to maintain a constant high cell density and high productivity of heterologous
protein was fed at a predetermined and preprogrammed rate, which maintained the
specific cell growth rate at an optimal level. The volumetric alpha-amylase
productivity achieved (1835 units l-1 h-1) from the two-stage, cyclic fed-batch
culture process was twofold higher than that of the fed-batch culture process.
The genetic stability of the recombinant strain and the design of optimal media
for growth and production stages are also critically important to a successful
implementation of the two-stage, cyclic fed-batch process for production of
heterologous protein.
PMID- 9650252
TI - Laccase from the white-rot fungus Trametes trogii.
AB - The white-rot fungus Trametes trogii excretes a main laccase showing a molecular
mass of 70 kDa, acidic isoelectric point and N-terminal sequence homologous to
that of several phenol oxidases. The purified enzyme oxidizes a number of
phenolic and non-phenolic compounds; recalcitrant molecules may be converted into
substrates by introducing, in the correct position, o- or p-orienting ring
activating groups.
PMID- 9650253
TI - Identification of tandemly repeated type VI cellulose-binding domains in an
endoglucanase from the aerobic soil bacterium Cellvibrio mixtus.
AB - Cellulose-binding domains (CBD) play a pivotal role during plant cell wall
hydrolysis by cellulases and xylanases from aerobic soil bacteria. Recently we
have reported the molecular characterisation of a single-domain endoglucanase
from Cellvibrio mixtus, suggesting that some cellulases produced by this aerobic
bacterium preferentially hydrolyse soluble cellulosic substrates. Here we
describe the complete nucleotide sequence of a second cellulase gene, celB, from
the soil bacterium C. mixtus. It revealed an open reading frame of 1863 bp that
encoded a polypeptide, defined as cellulase B (CelB) with a predicted Mr of 66
039. CelB contained a glycosyl hydrolase family 5 catalytic domain at its N
terminus followed by two repeated domains, which exhibited sequence identity with
type VI CBD previously found in xylanases. Full-length CelB bound to cellulose
while catalytically active truncated cellulase derivatives were unable to bind
the polysaccharide, confirming that CelB is a modular enzyme and that the type VI
CBD homologues were functional. Analysis of the biochemical properties of CelB
revealed that the enzyme hydrolyses a range of cellulosic substrates, although it
was unable to depolymerise Avicel. We propose that type VI CBD, usually found in
xylanases, provide an additional mechanism by which cellulases can accumulate on
the surface of the plant cell wall, although they do not potentiate cellulase
activity directly. The results demonstrate that C. mixtus, in common with other
aerobic bacteria, is able to produce cellulases that are directed to the
hydrolysis of cellulose in its natural environment, the plant cell wall.
PMID- 9650254
TI - Production of a new DNA vehicle for gene transfer using site-specific
recombination.
AB - Supercoiled DNA molecules, minicircles, were produced by in vivo site-specific
recombination. They contained exclusively the desired excisable fragment.
Recombination was driven by bacteriophage lambda integrase from a plasmid
substrate containing the attP and attB recombination sites in the same
orientation. Conditions for minicircle production within the lysogen Escherichia
coli D1210HP were optimised. Up to 1.5 mg minicircles could be produced per litre
bacterial culture, and the remaining, unrecombined plasmid comprised less than
about 15% of the minicircle produced. However minicircle multimers were also
produced, and comprised up to 30% of all minicircles synthesised. The par ABCDE'
locus from plasmid RK2 was introduced into the minicircle fragment, resulting in
minicircle dimers being reduced to less than 2% of all minicircles. The par A
gene encodes a resolvase that catalyses recombination at the multimer resolution
site in the parABCDE' locus. Minicircle multimers were also resolved when par A
was introduced downstream from the integrase gene of the lambda pL transcript in
D1210HP together with a multimer resolution site carried by the minicircle
fragment.
PMID- 9650255
TI - Overexpression of high-molecular-mass nitrile hydratase from Rhodococcus
rhodochrous J1 in recombinant Rhodococcus cells.
AB - High-molecular-mass nitrile hydratase (H-NHase, 530 kDa) is a cobalt-containing
enzyme produced by Rhodococcus rhodochrous J1. For efficient production of H
NHase in R. rhodochrous ATCC12674, several plasmids were constructed. The enzyme
was produced in the recombinant Rhodococcus cells only in the presence of an
upstream region (approximately 4 kb) of the H-NHase gene under the control of the
promoter for the amidase-NHase gene cluster from Rhodococcus sp. N-774. Although
H-NHase was produced as a soluble protein in the cells, the protein did not show
NHase activity. However, when the recombinant R. rhodochrous ATCC12674 cells were
cultured in the presence of amide compounds, such as crotonamide and
methacrylamide, markedly high NHase activity was detected, Gel-filtration
chromatography revealed that the NHases produced by the cells grown in the
presence and absence of the amide compounds had a molecular mass of more than 500
kDa and 50-80 kDa respectively. These results suggest that the amide compounds
are essential for subunit assembly to form an enzymatically active multimer. By
the use of the recombinant expression system, NHase activity 1.7 times higher
than that of the original strain, R. rhodochrous J1, was achieved.
PMID- 9650256
TI - Phosphate-independent expression of the carbon-phosphorus lyase activity of
Escherichia coli.
AB - On the basis of mutational analysis, the genes for phosphonate uptake and
degradation in Escherichia coli were shown to be organized in a 10.9-kb operon of
14 genes (named phnC to phnP) and induced by phosphate (P(i)) starvation [Metcalf
and Wanner (1993) J Bacteriol 175: 3430-3442]. The repression of phosphonate
utilization by P(i) has hindered both the biochemical characterization of the
carbon-phosphorus (C-P) lyase activity and the development of improved methods
for phosphonate biodegradation in biotechnology. We have cloned the genes phnG to
phnP (associated with C-P lyase activity) with the lac promoter to provide
expression of C-P lyase in the presence of P(i). A number of strains lacking
portions of the phn operon have been constructed. In vivo complementation of the
strains, in which phnC to phnP (including both Pn transport and catalysis genes)
or phnH to phnP (including only catalysis genes) was deleted, with plasmids
carrying various fragments of the phn operon revealed that the expression of phnC
phnP gene products is essential to restore growth on minimal medium with
phosphonate as the sole phosphorus source, while phnG-phnM gene products are
required for C-P lyase activity as assessed by in vivo methane production from
methylphosphonic acid. The minimum size of the DNA required for the whole-cell C
P lyase activity has been determined to be a 5.8-kb fragment, encompassing the
phnG to phnM genes. Therefore, there is no requirement for the phn CDE-encoded
phosphate transport system, suggesting that cleavage of the C-P bond may occur on
the outer surface of the inner membrane of E. coli cells, releasing the carbon
moiety into the periplasm. These data are in agreement with the observation that
phosphonates cannot serve as the carbon source for E. coli growth.
PMID- 9650257
TI - The effects of space flight on the production of monorden by Humicola fuscoatra
WC5157 in solid-state fermentation.
AB - The effect of space flight on the production of the antibiotic monorden on two
types of agar media, T8 and PG, by Humicola fuscoatra WC5157 was examined on
board the US Space Shuttle mission STS-77 in May 1996. Paired space-flight and
ground control samples were prepared using identical hardware, protocol, media,
and inoculum. Inoculation occurred simultaneously for both groups 2.5 after
launch. The flight and ground samples were allowed to grow for the entire 10-day
mission in a dark, thermally controlled (22 degrees C) environment. Post-flight
HPLC analysis of the flight and ground sample extracts indicated that the
production of monorden by H. fuscoatra WC5157 in the flight samples was higher
than in the ground samples in both agar media. In the T8 medium, the production
of monorden in the flight and ground samples was 11.6 +/- 3.5 micrograms and 8.9
+/- 1.1 micrograms respectively (30% increase). In the PG medium, the production
of monorden in the flight and ground samples was 23.8 +/- 3.3 micrograms and 8.2
+/- 2.2 micrograms respectively (190% increase). The production of monorden in
the flight and ground control samples was confirmed by HPLC-MS analysis.
PMID- 9650258
TI - The diversion of lactose carbon through the tagatose pathway reduces the
intracellular fructose 1,6-bisphosphate and growth rate of Streptococcus bovis.
AB - Twenty strains of Streptococcus bovis grew more slowly on lactose (1.21 +/- 0.12
h-1) then than on glucose (1.67 +/- 0.12 h-1), and repeated transfers or
prolonged growth in continuous culture (more than 200 generations each) did not
enhance the growth rate on lactose. Lactose transport activity was poorly
correlated with growth rate, and slow growth could not be explained by the ATP
production rate (catabolic rate). Batch cultures growing on lactose always had
less intracellular fructose 1,6-bisphosphate (Frul,6P2) than cells growing on
glucose (6.6 mM compared to 16.7 mM), and this difference could be explained by
the pathway of carbon metabolism. Glucose and the glucose moiety of lactose were
metabolized by the Embden-Meyerhoff-Parnas (EMP) pathway, but the galactose
moiety of lactose was catabolized by the tagatose pathway, a scheme that by
passed Frul,6P2. A mutant capable of co-metabolizing lactose and glucose grew
more rapidly when glucose was added, even though the total rate of hexose
fermentation did not change. Wild-type S. bovis grew rapidly with galactose and
melibiose, but these galactose-containing sugars were activated by galactokinase
and catabolized via EMP. On the basis of these results, rapid glycolytic flux
through the EMP pathway is needed for the rapid growth (more than 1.2 h-1) of S.
bovis.
PMID- 9650259
TI - Isolation and characterization of two bacteriocins of Lactobacillus acidophilus
LF221.
AB - Lactobacillus acidophilus LF221 produced bacteriocin-like activity against
different bacteria including some pathogenic and food-spoilage species. Besides
some lactic acid bacteria, the following species were inhibited: Bacillus cereus,
Clostridium sp., Listeria innocua, Staphylococcus aureus, Streptococcus D. L.
acidophilus LF221 produced at least two bacteriocins, acidocin LF221 A and
acidocin LF221 B, which were purified by ammonium sulphate precipitation, ion
exchange chromatography, hydrophobic interaction and reverse-phase FPLC. The
antibacterial substances were heat-stable, sensitive to proteolytic enzymes
(trypsin, pepsin, pronase, proteinase K) and migrated as 3500- to 5000-Da
proteins on sodium dodecyl sulphate/polyacrylamide gel electrophoresis. The
sequences of 46 amino-terminal amino acid residues of peptide A and 35 of peptide
B were determined. Among the residues identified, no modified amino acids were
found. No significant homology was found between the amino acid sequences of
acidocin LF221 A and other bacteriocins of lactic acid bacteria and 26% homology
was found between acidocin LF221 B and brevicin 27. L. acidophilus LF221 may be
of interest as a probiotic strain because of its human origin and inhibition of
pathogenic bacteria, especially clostridium difficile.
PMID- 9650260
TI - Biodegradation of atrazine under denitrifying conditions.
AB - Anaerobic biodegradation of atrazine by the bacterial isolate M91-3 was
characterized with respect to mineralization, metabolite formation, and
denitrification. The ability of the isolate to enhance atrazine biodegradation in
anaerobic sediment slurries was also investigated. The organism utilized atrazine
as its sole source of carbon and nitrogen under anoxic conditions in fixed-film
(glass beads) batch column systems. Results of HPLC and TLC radiochromatography
suggest that anaerobic biotransformation of atrazine by microbial isolate M91-3
involved hydroxyatrazine formation. Ring cleavage was demonstrated by 14CO2
evolution. Denitrification was confirmed by detection of 15N2 in headspace
samples of K15NO3-amended anaerobic liquid cultures. In aquatic sediments,
mineralization of uniformly ring-labeled [14C]atrazine occurred in both M91-3
inoculated and uninoculated sediment. Inoculation of sediments with M91-3 did not
significantly enhance anaerobic mineralization of atrazine as compared to
uninoculated sediment, which suggests the presence of indigenous organisms
capable of anaerobic atrazine biodegradation. Results of this study suggest that
the use of M91-3 in a fixed-film bioreactor may have applications in the
anaerobic removal of atrazine and nitrate from aqueous media.
PMID- 9650261
TI - Rapid atrazine mineralisation in soil slurry and moist soil by inoculation of an
atrazine-degrading Pseudomonas sp. strain.
AB - The evaluation of pesticide-mineralising microorganisms to clean-up contaminated
soils was studied with the widely applied and easily detectable compound
atrazine, which is rapidly mineralised by several microorganisms including the
Pseudomonas sp. strain Yaya 6. The rate of atrazine removal was proportional to
the water content of the soil and the amount of bacteria added to the soil. In
soil slurry, 6 mg atrazine kg soil-1 was eliminated within 1 day after
application of 0.3 g dry weight inoculant biomass kg soil-1 and within 5 days
when 0.003 g kg soil-1 was used. In partially saturated soil (60% of the maximal
water-holding capacity) 15 mg atrazine kg soil-1 was used. In unsaturated soil,
about 60% [U-ring-14C] atrazine was converted to 14CO2 within 14 days. Atrazine
was very efficiently removed by the inoculant biomass, not only in soil that was
freshly contaminated but also in soil aged with atrazine for up to 260 days. The
bacteria exposed to atrazine in unsaturated sterile soil were still active after
starvation period of 240 days: 15 mg newly added atrazine kg soil-1 was
eliminated within 5 days.
PMID- 9650262
TI - A review of radiologically important trace elements in human bones.
AB - The authors recently compiled and reviewed the literature for minor and trace
elements in human bones and teeth as a part of an International Atomic Energy
Agency (IAEA) study. Various aspects of elemental composition, analytical
methodologies, quality assurance and quality control methods for hard tissue
analysis were evaluated. Important data on selected radiologically important
elements (Cs, Pu, Ra, Sr, Th, and U) in calcified tissue from various countries
are discussed. The results of this compilation study suggest a need for new
reference materials with matrix properties similar to bones including one with
separated cortical and trabecular segments.
PMID- 9650263
TI - An investigation of the imaging characteristics of the Y2O2S:Eu3+ phosphor for
application in X-ray detectors of digital mammography.
AB - Y2O2S:Eu laboratory prepared screens were evaluated as mammographic image
receptors and were compared to similarly prepared screens of Gd2O2S:Tb and
Y2O2S:Tb phosphor materials, often used in X-ray imaging detectors. The
evaluation was performed by determining the Modulation Transfer Function (MTF)
and the spatial frequency dependent Detective Quantum Efficiency (DQE). Y2O2S:Eu
exhibited higher DQE values at low frequencies and given its good spectral
matching with digital optical detectors, it may be appropriate for use in X-ray
digital mammography.
PMID- 9650264
TI - Cytotoxicity and mutagenicity of a 2,4,6-trinitrotoluene (TNT) and hexogen
contaminated soil in S. typhimurium and mammalian cells.
AB - The toxicity and mutagenicity of aqueous and organic extracts of soil
contaminated with TNT, TNT metabolites and hexogen was determined in mammalian
cell lines and in prokaryotic cells. The prokaryotic toxicity was determined via
the colony forming ability of Salmonella typhimurium (strains TA 98 and TA 100).
The same strains were used to test mutagenicity in the Ames test. The mammalian
toxicity was analyzed in human fibroblasts by the inhibition of cell growth and
cell viability (MTT assay). The mammalian mutagenicity was tested with the HPRT
test in V79 cells (hamster lung). The aqueous soil extract did not reveal
toxicity or mutagenicity in any of the tests performed. The DMSO/ethanol extract
showed toxicity and mutagenicity in S. typhimurium. Thereby strain TA 98 was more
sensitive than strain TA 100. In human fibroblasts cell growth was strongly
inhibited, whereas no reduction of cell viability was found in the MTT test.
Mutagenicity of the DMSO/ethanol extract of the soil was demonstrated in V79
cells.
PMID- 9650265
TI - Identification of lipophilic pollutants discharged from a Finnish pulp and paper
mill.
AB - Lipophilic organic compounds originating from kraft pulping and papermaking were
identified by straight gas chromatography/mass spectrometry (GC/MS) analyses.
Samples analyzed included a primary clarifier effluent (PE) and a secondary
clarifier effluent (SE) from the activated sludge treatment plant of a Finnish
ECF-bleached (Elementally Chlorine Free) kraft pulp and paper mill. Liquid-liquid
extraction composition of PE was compared with solid phase extraction (SPE) and
dialysis of a semipermeable membrane device (SPMD) exposed to PE. Dichloromethane
extracts of particulate material isolated from PE, sludges from both the primary
and secondary clarifier, a sediment collected in the vicinity of the mill and
whitefish subacutely exposed to the secondary treatment effluent were also
investigated. Typical pulp mill-related compounds such as terpenes, terpenoids
and aromatic compounds were identified in PE whereas these were non-detectable in
SE. For example, thunbergene, thunbergol, squalene, longifolene and derivatives
of abietic acid were observed in PE. Alkylated polycyclic aromatics were major
compounds identified in the sediment sample with retene (C4-alkyl phenanthrene)
as a predominant component.
PMID- 9650266
TI - Kinetics of biodegradation of di-n-butyl phthalate in continuous culture system.
AB - The characteristics of microbial growth and kinetics of DBP biodegradation was
studied in a continuous culture system using DBP as a sole source of carbon. The
results showed that, at high substrate concentration, the microbial growth was
inhibited by DBP, and can be described by the Haldane model. Kinetic parameters
based on Haldane substrate inhibition were evaluated. The values were mu(m) =
0.38 h-1, Ki = 86 mg/l, Ks = 28 mg/l. The DBP concentration to avoid substrate
inhibition was inferred theoretically and determined to be 49 mg/L.
PMID- 9650267
TI - The efficiency of different phenol-degrading bacteria and activated sludges in
detoxification of phenolic leachates.
AB - Phenolic composition, toxicity and biodegradability of three different phenolic
leachates/samples was studied. Samples A and C were the leachates from the oil
shale industry spent shale dumps at Kohtla-Jarve, Estonia. Sample B was a
laboratory-prepared synthetic mixture of 7 phenolic compounds mimmicking the
phenolic composition of the leachate A. Toxicity of these 3 samples was analyzed
using two photobacterial test (BioTox and Microtox), Daphnia test (DAPHTOXKIT F
pulex) and rotifiers' test (ROTOXKIT F). All the LC50 values were in the range of
1-10%, leachate A being the most toxic. The growth and detoxifying potential
(toxicity of the growth medium was measured using photobacterial tests) of 3
different phenol-utilizing bacteria and acclimated activated sludges was studied
in shake-flask cultures. 30% leachate A (altogether 0.6 mM total phenolic
compounds) was too toxic to rhodococci and they did not grow. Cell number of
Kurthia sp. and Pseudomonas sp. in 30% leachate A increased by 2 orders of
magnitude but despite of the growth of bacteria the toxicity of the leachate did
not decrease even by 7 weeks of cultivation. However, if the activated sludge was
used instead of pure bacterial cultures the toxicity of the 30% leachate A was
eliminated already after 3 days of incubation. 30% samples B and C were
detoxified by activated sludge even more rapidly, within 2 days. As the
biodegradable part of samples A and B should be identical, the detoxification of
leachate A compared to that of sample B was most probably inhibited by inorganic
(e.g. sulphuric) compounds present in the leachate A. Also, the presence of toxic
recalcitrant organic compounds in the leachate A (missed by chemical analysis)
that were not readily biodegradable even by activated sludge consortium should
not be excluded.
PMID- 9650268
TI - The 'two-phase closed bottle test'--a suitable method for the determination of
'ready biodegradability' of poorly soluble compounds.
AB - The Two-Phase Closed Bottle test (BODIS test) is a cost-effective supplement of
the existing OECD tests for ready biodegradability (OECD 301) due to its entire
compatibility with them and its particular suitability for testing poorly soluble
compounds. The comparison of a number of test data from this and other ready
biodegradability tests showed that the BODIS test has a similar stringency in
terms of the attainment of the pass level and the time window criterion as well.
A significant influence of the strength of the bacterial inoculum on the test
results was not observed.
PMID- 9650269
TI - Uptake of moderately hydrophobic chlorophenols from water by semipermeable
membrane devices (SPMDs) and by goldfish (Crassius auratus).
AB - Semipermeable membrane devices (SPMDs) filled with triolein and goldfish
(Crassius auratus) were simultaneously exposed to nine moderately hydrophobic
chlorophenols in a laboratory continuous-flow experiment. The results showed that
the test compounds were concentrated in the device to an extent very closed to
that in fish. The overall uptake rate constants (Ku) and average pollutant
sampling rates (Rs) were similar for both SPMDs and goldfish. We conclude that
the SPMDs can be used to estimate the levels of moderately hydrophobic
chlorophenols in field water as an environmental monitor.
PMID- 9650270
TI - Environmental biotechnology regulatory affairs. Web alert.
PMID- 9650271
TI - Molecular genetics of bacterial attachment and biofouling.
AB - Microbial adhesion to animate or inert surfaces is potentially mediated by
nonspecific physical or specific ligand-receptor interactions. Growth and
survival of the microbial community or biofilm then depends on adaptation to a
series of changing environmental milieux. Within the realm of cell-cell
interaction, recent advances suggest that flagella, fimbriae and other protein
receptors are essential for bacterial attachment to surfaces. There has also been
profound progress in the elucidation of genes and molecules necessary for
bacterial attachments to surfaces and subsequent biofilm formation.
PMID- 9650272
TI - The molecular biology of chitin digestion.
AB - Chitinases catalyze the hydrolysis of chitin, an unbranched polymer of beta-1,4-N
acetylglucosamine. In recent years, soil-borne microorganisms that produce
chitinases are considered as potential biocontrol agents against fungi and
nematodes which causes diseases of agricultural crops. Chitinases also play an
important physiological and ecological role in ecosystems as recyclers of chitin,
by generating carbon and nitrogen sources. Many chitinases of varied organisms
have been isolated and their corresponding genes cloned.
PMID- 9650273
TI - Bioenergetics of marine bacteria.
AB - Some marine bacteria have a special energy-transducing mechanism that is
different from those found in Escherichia coli or most of the freshwater and
terrestrial bacteria. These marine bacteria specifically require Na+ for their
growth and utilize a Na+ circuit for various cellular functions. So far, three
types of primary Na+ pump have been identified (i.e. respiration-dependent,
decarboxylase-driven and Na+ ATP synthase). Among them, the first type of Na+
pump plays the major role in the marine environment. Recently, the gene sequence
and distribution of this Na+ pump have been clarified. In addition, information
on genetics and the ecological significance of Na+ driven flagellar motors has
also been accumulating. This recent progress in the research of the 'Na+ world'
is revealing an interesting way of life that is unique to marine microorganisms.
PMID- 9650274
TI - Molecular approaches to measuring microbial marine pollution.
AB - Developments in the rapid detection of pathogens (PCR and its variations) and
molecular typing of strains isolated from the ecosystem illustrate the
stimulation of research due to the recent foodborne and waterborne disease
outbreaks.
PMID- 9650275
TI - Strengthening the biological weapons convention and implications on the
pharmaceutical and biotechnology industry.
AB - The development, production, stockpiling, and use of biological weapons are
banned by the 1972 Biological Weapons Convention (BWC). Reflecting the realities
of the Cold War era in which it was negotiated, the BWC lacks means for
compliance verification or enforcement. International efforts to remedy this
deficiency are accelerating in the face of evidence that covert biological weapon
programs are proliferating at the national and subnational levels.
PMID- 9650276
TI - Specifications for biotechnology-derived protein drugs.
AB - Specifications are the regulatory and legal standards that a product must meet to
be suitable for use in humans. Specifications evolve in parallel with drug
development and are refined prior to marketing authorization and, in some cases,
after marketing. Recent changes in regulatory procedures for biotechnology
derived protein products have placed much emphasis on the use of characterization
and final product specifications to provide assurance of overall quality of these
products. In addition, harmonized guidelines for the testing and specifications
for biotechnology products have been developed through the International
Conference on Harmonization process. The availability of sensitive, quantitative,
and specific analytical methods for characterization has made this possible, thus
providing regulatory flexibility in the development of biotechnology-derived
protein products. Further refinement of these analytical tools will undoubtedly
enhance this regulatory flexibility.
PMID- 9650277
TI - Heterozygosity-fitness correlations: new perspectives on old problems.
AB - Heterozygosity-fitness correlations (HFC) have been studied in various organisms
for more than two decades, but they are not universal. Although their
detectability is limited by several factors (null alleles, inaccuracy of the
phenotypic description of fitness, small sample sizes) the correlations appear
intrinsically weak and often inconsistent across samples. Determining the origins
of HFC is therefore a complex task. However, this issue might soon be resolved
provided clear hypotheses and definitions are used (especially, if the problem of
the neutrality of allozyme variation is not identified with the related issue of
HFC), as well as new empirical (molecular markers) & theoretical (statistical
models) tools.
PMID- 9650278
TI - Gene conversion disparity in yeast: its extent, multiple origins, and effects on
allele frequencies.
AB - The extent of disparity in gene conversion direction in yeast (Saccharomyces
cerevisiae) is important for recombination mechanisms and for effects of
conversion on allele frequencies in populations. An analysis of published and
unpublished data demonstrates that yeast frequently shows significant and
extensive conversion disparity, contrary to many published statements. All types
of mutation--base-substitutions, frameshifts and longer deletions and additions-
can show significant 6:2/2:6 and/or 5:3/3:5 disparity. There was little
correlation between the occurrence of 6:2/2:6 and 5:3/3:5 disparities; when both
were significant, they were more often in opposite directions than in the same
direction. Surprisingly, there was little correlation between a mutation's
molecular nature and its disparity properties, which generally seem
unpredictable. Disparity in yeast has multiple origins. From the equations
discussed, all disparity types can be explained by one or more of: correction
direction disparity, chromatid invasion disparity (including cases caused by
different frequencies of double-strand breaks or gaps in nonsister homologous
chromatids), strand invasion disparity, and different correction frequencies for
the two types of mispair for a heterozygous mutation. Levels of overall disparity
and of conversion frequency mean that conversion must often change allele
frequencies in sexually reproducing yeast populations.
PMID- 9650279
TI - Chloroplast DNA recognizes three refugial sources of European oaks and suggests
independent eastern and western immigrations to Finland.
AB - Refugial differentiation and routes of postglacial migration are major
determinants of the patterns of geographical variation we see in natural
populations today. We used patterns of chloroplast DNA (cpDNA) variation to
investigate the postglacial colonization history of the European oak species
Quercus robur and Q. petraea. By sequencing two cpDNA segments using universal
primers, we revealed four polymorphic sites which identify four cytotypes with
characteristic geographical distributions. Of these, the principal eastern,
central and western cytotypes divide the range into three longitudinal zones,
each extending from the south to the north of Europe. This corroborates the idea
that the postglacial colonization started from three distinct southerly refugia.
The fourth cytotype, restricted to East Anglia, was probably derived from the
western type postglacially. As a special problem, we addressed the controversial
origin of Q. robur at its northern limits in south-western Finland, where it
currently occupies a narrow coastal zone disjunct from the remaining oak range.
Using a PCR-RFLP assay that discriminates the eastern cytotype, a contact zone of
two cytotypes was identified in the region of the Salpausselka ridges. This
suggests that the marginal northern occurrence was independently colonized both
from the east and from the west, across the Baltic Sea.
PMID- 9650280
TI - Genetic relationships within the genus Beta determined using both PCR-based
marker and DNA sequencing techniques.
AB - The sequences of ITS1 of the internal transcribed spacer regions of nuclear
ribosomal DNA from 11 species or subspecies in four sections of the genus Beta
were compared. Phylogeny of these wild beet taxa was inferred from the sequence
data using phenetic and phylogenetic analyses. Multiple accessions from the same
11 taxa were subjected to random amplified polymorphic DNA (RAPD) analysis, and
the data were analysed phenetically. With both molecular techniques and each
analysis, three distinctive groups were formed: species from section Beta formed
one group; species from section Procumbentes formed a very distinct group; and
species from both section Nanae and section Corollinae clustered together forming
the third group, which is closer to Beta than Procumbentes. The RAPD data
revealed within-section interspecies relationships that are consistent with those
reported previously; this was not always the case using the single-locus sequence
data.
PMID- 9650281
TI - mtDNA phylogeography and postglacial patterns of subdivision in the meadow
grasshopper Chorthippus parallelus.
AB - A 300 bp portion of the mitochondrial cytochrome oxidase subunit I (COI) gene was
used to investigate the intraspecific genetic structure of the European meadow
grasshopper Chorthippus parallelus. Levels of genetic subdivision between
geographical regions in Europe were assessed using the KST statistic and revealed
patterns indicative of the postglacial history of this organism. Northern
European populations are shown to share a very recent common ancestor with, and
hence originate from, a Balkan expansion. Genetic distances between these areas
and both southern Italy and central Spain are shown to be approximately equal,
even though only the Spanish form is recognized as a distinct subspecies.
Distance estimates indicate that the common ancestor of the two subspecies lived
more than one glacial cycle ago, and the refugial populations have probably been
diverging in isolation for five or six glacial cycles (approximately equal to
550,000 years). Comparisons are made to the analysis of a similar data set using
an anonymous nuclear DNA marker (Cooper et al., 1995). Although the structure
revealed is generally very similar, differences in the location of transition
zones between different genetic forms of C. parallelus may reflect the different
historical assortment of these molecules.
PMID- 9650282
TI - Inheritance of behavioural differences between two interfertile, sympatric
species, Drosophila silvestris and D. heteroneura.
AB - The Hawaiian fly species, Drosophila silvestris and D. heteroneura, are sympatric
and interfertile but show strong behavioural isolation and major differences in
male aggressive behaviour and the associated morphology. As a first step in
elucidating the genetic control of the differences between these species, we
examined the mating and aggressive behaviour of their reciprocal F1 hybrids. The
latency to the first wing vibration and the latency to copulate did not differ
significantly between the parental species. However, D. heteroneura females had a
very low tendency to copulate with D. silvestris males, rarely mating during the
observation period. The duration of copulation also differed significantly; same
species pairs of D. silvestris had copulations that lasted about 50% longer than
those of same-species pairs of D. heteroneura. The hybrids were intermediate
between the parental species for both the tendency to copulate with D. silvestris
males and the duration of copulation, suggesting codominance or polygenic
inheritance for those traits. The aggression traits that we scored were the leg
posture and wing extension during early aggression, and the leg posture and head
position during escalated aggression. The parental species showed clear
differences for each of these traits. The F1 hybrids resembled one parent or the
other, without showing intermediate values, suggesting single-gene dominance or
threshold expression of many genes for those traits. None of the courtship or
aggressive traits showed X-chromosomal effects, although the head shape of
hybrids is influenced by genes on the X chromosome. It is difficult to reconcile
the patterns of inheritance of aggressive behaviour and the lack of an X
chromosomal effect with the hypothesis that these traits are influenced by a
coadapted gene complex.
PMID- 9650283
TI - Substrate-dependent enantioselectivity of a novel hydantoinase from Arthrobacter
aurescens DSM 3745: purification and characterization as new member of cyclic
amidases.
AB - A hydantoinase from Arthrobacter aurescens DSM 3745 has been purified to
homogeneity with a yield of 77% using a three-step purification procedure. The
active enzyme is a tetramer consisting of four identical subunits, each with a
molecular mass of 49670 Da as determined by mass spectrometry. The N-terminal
amino acid sequence of the enzyme indicates sequence identities to cyclic
amidases involved in the nucleotide metabolism as the D-hydantoinase from
Agrobacterium radiobacter (53%), the D-selective dihydropyrimidinase from
Bacillus stearothermophilus (38%), the allantoinase from Rana catesbeiana (26%),
as well as to the catalytic subunit of the urease from Helicobacter pylori (50%).
However, all studies based on substrate-dependent growth, induction and catalytic
behavior documented the novelty of the bacterial hydantoinase and that its
physiological role is not related to any of these enzymes or known metabolic
pathways. Its substrate specificity differs from hydantoinases listed in Enzyme
Nomenclature and is rather more predominant for the cleavage of aryl- than for
alkyl-hydantoin derivatives. It is shown that the stereoselectivity of this
enzyme depends on the substrate used for bioconversion: although it is strictly L
selective for the cleavage of D,L-5-indolylmethylhydantoin, it appears to be D
selective for the hydrolysis of D,L-methylthioethylhydantoin. Due to these
findings we conclude that this novel bacterial hydantoinase should be classified
as a new member of the EC-group 3.5.2 of cyclic amidases.
PMID- 9650284
TI - Effect of the dilution rate on the mode of oscillation in continuous cultures of
Saccharomyces cerevisiae.
AB - The growth properties of the asymmetric budding yeast Saccharomyces cerevisiae
were analysed during spontaneous oscillations in continuous cultures at varying
dilution rates D. The length of the oscillation period changed between 1.4 and 14
h in response to the decrease of dilution rate from 0.15 to 0.05 h-1. The
distribution of parent and daughter cells in the population was determined
microscopically after staining the bud scars and DNA. Most of the data obtained
fits a theoretical population balance model assuming two-classes of
subpopulations and integer ratios between the generation times of both classes.
Some data has to be described by an extended population model assuming there is
one parent and two daughter cell classes. How changes of dilution rate may cause
an accidental switch of the mode of oscillation is demonstrated. Glucose
consumption and metabolite production were measured off-line by enzymatic methods
and gas exchange was monitored on-line. All these data of one period point to
internal and external signals responsible for the synchronisation of the cell
cycle.
PMID- 9650285
TI - Subcellular localization of enzyme activities in chemostat-grown murine myeloma
cells.
AB - As part of the development of structured models for the metabolism of myeloma
cells in suspension culture, a study was made of the subcellular localization of
key enzymes of glucose and glutamine metabolism. Steady state chemostat cultures
of the mouse myeloma SP2/0-Ag14 were used as a reproducible source of biomass.
Homogenates of the cells, obtained via mechanical disruption, were separated into
a mitochondrial and a cytosolic fraction via differential centrifugation. The
following conclusions are drawn: (1) approximately one fifth of the hexokinase
activity of cell-free homogenates is associated with the mitochondria; (2) a
malate-aspartate shuttle may operate for oxidation of cytosolic NADH, as
indicated by high levels of malate dehydrogenase and aspartate aminotransferase
in both particulate and soluble fractions; (3) the pentose phosphate pathway and
isocitrate dehydrogenase may contribute to the provision of cytosolic NADPH; (4)
phosphoenolpyruvate carboxykinase and pyruvate kinase, which are present in high
activities, are exclusively cytosolic and probably play a key role in glutamine
metabolism; (5) oxidation of glutamine via these enzymes leads to the formation
of pyruvate that enters the same pool as pyruvate generated by glycolysis. As a
result, lactate and alanine formation can occur from both glucose and glutamine.
PMID- 9650286
TI - Expression in Saccharomyces cerevisiae of antigenically and enzymatically active
recombinant glutamic acid decarboxylase.
AB - Glutamic acid decarboxylase (GAD) is one of the major autoantigens found in
insulin-dependent (Type 1) diabetes mellitus (IDDM). A novel hybrid form of GAD
was created by fusing amino acids 1-101 of the human GAD67 protein to amino acids
96-585 of the human GAD65 protein. This hybrid GAD67/65 was expressed
constitutively under the control of the phosphoglycerate kinase promoter (PGK1)
in the yeast Saccharomyces cerevisiae. Enzymatically active GAD was prepared from
yeast lysates by a one-step purification on an affinity column using GAD-1
antibody. The purified hybrid GAD67/65 was radiolabelled with iodine-125 and
tested in an immunoprecipitation assay with IDDM sera. Results obtained using the
recombinant yeast hybrid GAD67/65 were very similar to those obtained using 125I
labelled porcine GAD. Recombinant yeast hybrid GAD67/65 should have utility for
diagnosis and presymptomatic detection of IDDM.
PMID- 9650287
TI - Review of ionic models of vagal-cardiac pacemaker control.
AB - Mathematical models of ion currents in pacemaker cells of the heart and their
associated modulation by vagal stimulation have provided numerous insights into
the ionic mechanisms underlying parasympathetic control of heart rate. In this
article, ionic models described in the literature are reviewed and compared, with
a view to examining their effectiveness in reproducing known chronotropic
responses to vagal stimulation.
PMID- 9650288
TI - Modelling the dynamics of LCMV infection in mice: conventional and exhaustive CTL
responses.
AB - Lymphocytic choriomeningitis virus (LCMV) infection in mice provides an example
of an extraordinarily dynamic process with an extreme sensitivity of phenotype of
infection to parameters of virus/host interaction. A mathematical model is
developed to examine the dynamics of virus-specific cytotoxic T lymphocyte (CTL)
response for LCMV infection in mice. The model, formulated by a system of
nonlinear delay-differential equations, considers the interacting populations of
viruses, precursor CTLs, terminally differentiated effector CTLs and total virus
antigen load. Clonal elimination of virus-specific cytotoxic T cells in high-dose
LCMV-Docile infection represents an example of the classical phenomenon--high
zone tolerance. To describe both conventional and exhaustive CTL responses in the
acute phase of LCMV-D infection two mechanisms are invoked: the high virus
antigen load inhibition of T-cells proliferation via energy induction and the
activation-induced cell death by apoptosis. Parameters of the model,
characterizing the rates of virus and CTL production and elimination in spleen,
are estimated by assimilating with the model data on the LCMV-D infection in
C57BL/6 mice for low-, moderate- and high-dose infections. It is suggested that
not only the clonal expansions have to be described in mathematical models as
being virus regulated but also the later phases of primary immune response. Down
regulation of the primary CTL response is controlled by a network of mechanisms
inducing anergy and apoptosis in activated T cells. The model is used to
investigate the effect of variations in virus and CTL response parameters on LCMV
infection outcome and suggest predictions for experimental studies, in particular
the phenotype of LCMV-WE infection in C57BL/6 as a function of initial virus
doses.
PMID- 9650289
TI - Evolution of the immune repertoire with and without somatic DNA recombination.
AB - Repertoire of an immune system is a set of antigen receptors each having a unique
specificity to bind an antigen. In many vertebrate species, antigen receptors are
produced via combinatorial arrangements of DNA segments in specialized immune
cells. Due to this molecular mechanism, repertoire of vertebrate species is
potentially very large. The diversity of repertoire is thought to guarantee
recognition of most ill-causing micro-organisms. In vertebrate species however,
similar editing of DNA segments has not been demonstrated to take place. Immune
system of invertebrate species therefore seems to operate in a distinct manner
from that of vertebrate species. Using an evolutionary model in which organisms
struggle to fight infections, we attempt to understand why some species use a
more diverse set of antigen receptors than others. Individuals in our model
either use somatic DNA recombination to produce antigen receptors (as in
vertebrates) or do not use such a mechanism (as in vertebrates). We found that
individuals having an invertebrate-like immune system came to employ only a few
antigen receptors to recognize a set of pathogens whereas those with a vertebrate
like immune system use a larger set of more specific antigen receptors to
recognize the same set of pathogens. Our interpretation of this finding is that
because the genetics of the immune system imposed different constraints on the
evolutionary process, two distinct recognition strategies have been adapted by
these species.
PMID- 9650290
TI - Analysis of a reduced model of corticotroph action potentials.
AB - We have previously described a model for corticotroph plasma membrane
electrophysiology [LeBeau et al. (1997). Biophysical Journal 73, 1263-1275]. The
model is a Hodgkin-Huxley-like formalism consisting of six coupled ordinary
differential equations. Analysis of this model showed that Ca2+ action potentials
could be induced by an increase in the L-type voltage-sensitive Ca2+ current.
Thus we have demonstrated a putative causal link between an increase in the
corticotroph Ca2+ current and action potential generation. We report here the
reduction of the model to one with three equations, the behaviour of which was
found to correspond well with that of the full model. The reduced model was then
subjected to fast-slow subsystem analysis, which revealed the mechanistic
interaction between the membrane potential and intracellular Ca2+ concentration
that underlies action potential generation. Insights obtained from this analysis
were used to investigate experimentally observed aspects of corticotroph
electrophysiology such as spontaneous electrical activity, bursting action
potentials, and observations from anode break excitation experiments.
PMID- 9650291
TI - Host spatial heterogeneity and extinction of an SIS epidemic.
AB - Spatially explicit epidemic models explore population-level consequences of
interactions between neighboring infectious and susceptible individuals. Most
such models equate local and global host density, so that each individual
interacts with the same number of neighbors. But many natural populations exhibit
heterogeneity in local abundance. Therefore, we let host dispersion vary from
uniform to clumped in a spatial epidemic with recovery. We analytically
approximated the epidemic with a branching process to show how the probability of
pathogen extinction could depend on the degree of host clumping. We then
simulated the detailed model across a range of parameter combinations. Both
approaches to the problem indicate that host spatial aggregation strongly
increases the chance of pathogen extinction.
PMID- 9650292
TI - "Critical slowing down" in time-to-extinction: an example of critical phenomena
in ecology.
AB - We study a model for two competing species that explicitly accounts for effects
due to discreteness, stochasticity and spatial extension of populations. The two
species are equally preferred by the environment and do better when surrounded by
others of the same species. We observe that the final outcome depends on the
initial densities (uniformly distributed in space) of the two species. The
observed phase transition is a continuous one and key macroscopic quantities like
the correlation length of clusters and the time-to-extinction diverge at a
critical point. Away from the critical point, the dynamics can be described by a
mean-field approximation. Close to the critical point, however, there is a
crossover to power-law behavior because of the gross mismatch between the largest
and smallest scales in the system. We have developed a theory based on surface
effects, which is in good agreement with the observed behavior. The course
grained reaction-diffusion system obtained from the mean-field dynamics agrees
well with the particle system.
PMID- 9650293
TI - In vitro sulfotransferase activity of NoeE, a nodulation protein of Rhizobium sp.
NGR234.
AB - Soil bacteria of the genera Azorhizobium, Bradyrhizobium, and Rhizobium liberate
morphogenetic lipochitin-oligosaccharides (Nod factors) into legume rhizospheres.
Nod factors, which are synthesized by the products of rhizobial nodulation (nod)
genes, vary in core length as well as in the number and type of substitutions. In
Rhizobium sp. NGR234, the N-acylated pentamers of N-acetyl-D-glucosamine carry an
O-methylfucose group on the reducing terminus that is substituted, on a mutually
exclusive basis, with either an acetyl or a sulfuryl group. A sulfotransferase
encoded by noeE is required for adjunction of activated sulfate donated by 3'
phosphoadenosine 5'-phosphosulfate (PAPS). Here we show that when expressed in
NGR234 cured of its symbiotic plasmid (= ANU265) or when purified as a fusion
protein (MBP-NoeE), NoeE transfers sulfate from PAPS to fucosylated lipochitin
oligosaccharides. Enzyme assays showed that sulfotransferase activity is
dependent on the presence of an acyl group (stearic and vaccenic acids were
tested) since no activity was detected when fucosylated oligochitins (oligomers
of two to six N-acetyl-D-glucosamine units) were used as substrates. Thus, NoeE
is unique in that it is the only characterized sulfotransferase that is specific
for fucosylated Nod factors. It probably acts after NodA, which acylates the
amino-sugar backbone.
PMID- 9650294
TI - A virulence-associated, 6.4-kb, double-stranded RNA from Rhizoctonia solani is
phylogenetically related to plant bromoviruses and electron transport enzymes.
AB - We have recently shown that acquisition of a 6.4-kb, double-stranded (ds) RNA
(M1) by hyphal anastomosis is associated with enhanced vigor and virulence,
whereas its removal by hyphal tipping correlates with diminished virulence in the
plant-pathogenic basidiomycete Rhizoctonia solani. The M1 dsRNA is not
encapsidated by a typical nucleocapsid, has a circular and/or concatemeric form,
and is associated with the mitochondrial and cytosolic fractions. M1 possesses
six open reading frames (ORFs) the longest of which (ORF 2) is located on the (+)
strand, and encodes a putative polypeptide consisting of 1,747 amino acids or
199.4 kDa. This polypeptide has a significant amino acid sequence similarity,
including six conserved helicase domains and an ATP/GTP binding motif, with the
1A protein of broad bean mottle virus (BBMV) and other bromoviruses. ORF 5, which
is located on the (-) strand of M1 and is complementary to a region of ORF 2,
codes for a putative polypeptide that has a significant amino acid sequence
similarity with the cytochrome c oxidase assembly factor. This complementarity
provides direct evidence suggesting that the long-standing hypothesis of viruses
evolving from cellular genes may be valid.
PMID- 9650295
TI - Cell-to-cell movement of beet necrotic yellow vein virus: I. Heterologous
complementation experiments provide evidence for specific interactions among the
triple gene block proteins.
AB - Cell-to-cell movement of beet necrotic yellow vein virus (BNYVV) requires three
proteins encoded by a triple gene block (TGB) on viral RNA 2. A BNYVV RNA 3
derived replicon was used to express movement proteins to functionally substitute
for the BNYVV TGB proteins was tested by coinoculation of TGB-defective BNYVV
with the various replicons to Chenopodium quinoa. Trans-heterocomplementation was
successful with the movement protein (P30) of tobacco mosaic virus but not with
the tubule-forming movement proteins of alfalfa mosaic virus and grapevine
fanleaf virus. Trans-complementation of BNYVV movement was also observed when all
three TGB proteins of the distantly related peanut clump virus were supplied
together but not when they were substituted for their BNYVV counterparts one by
one. When P30 was used to drive BNYVV movement in trans, accumulation of the
first TGB protein of BNYVV was adversely affected by null mutations in the second
and third TGB proteins. Taken together, these results suggest that highly
specific interactions among cognate TGB proteins are important for their function
and/or stability in planta.
PMID- 9650296
TI - Differential involvement of indole-3-acetic acid biosynthetic pathways in
pathogenicity and epiphytic fitness of Erwinia herbicola pv. gypsophilae.
AB - Erwinia herbicola pv. gypsophilae (Ehg), which induces galls on Gypsophila
paniculata, harbors two major pathways for indole-3-acetic acid (IAA) synthesis,
the indole-3-acetamide (IAM) and indole-3-pyruvate (IPyA) routes, as well as
cytokinin biosynthetic genes. Mutants were generated in which the various
biosynthetic routes were disrupted separately or jointly in order to assess the
contribution of IAA of various origins and cytokinins to pathogenicity and
epiphytic fitness. Inactivation of the IAM pathway or cytokinin biosynthesis
caused the largest reduction in gall size. Inactivation of the IPyA pathway
caused a minor, nonsignificant decrease in pathogenicity. No further reduction in
gall size was observed by the simultaneous inactivation of both IAA pathways only
or in combination with that of cytokinin production. However, inactivation of the
IPyA pathway caused a 14-fold reduction in the population of Ehg on bean plants.
Inactivation of the IAM pathway or cytokinin production did not affect epiphytic
fitness. While the apparent transcriptional activity of iaaM-inaZ fusion
increased slightly in cells of Ehg on bean and gypsophila leaves, compared with
that in culture, very high levels of induction were observed in cells injected
into gypsophila stems. In contrast, moderate levels of induction of ipdC-inaZ in
Ehg were observed on leaves of these plants and in gypsophila stems, when
compared with that in culture. These results suggest that the IAM pathway is
involved primarily in gall formation and support the main contribution of the
IpyA pathway to the epiphytic fitness of this bacterial species.
PMID- 9650297
TI - Induced resistance responses in maize.
AB - Systemic acquired resistance (SAR) is a widely distributed plant defense system
that confers broad-spectrum disease resistance and is accompanied by coordinate
expression of the so-called SAR genes. This type of resistance and SAR gene
expression can be mimicked with chemical inducers of resistance. Here, we report
that chemical inducers of resistance are active in maize. Chemical induction
increases resistance to downy mildew and activates expression of the maize PR-1
and PR-5 genes. These genes are also coordinately activated by pathogen infection
and function as indicators of the defense reaction. Specifically, after pathogen
infection, the PR-1 and PR-5 genes are induced more rapidly and more strongly in
an incompatible than in a compatible interaction. In addition, we show that
monocot lesion mimic plants also express these defense-related genes and that
they have increased levels of salicylic acid after lesions develop, similar to
pathogeninfected maize plants. The existence of chemically inducible disease
resistance and PR-1 and PR-5 gene expression in maize indicates that maize is
similar to dicots in many aspects of induced resistance. This reinforces the
notion of an ancient plant-inducible defense pathway against pathogen attack that
is shared between monocots and dicots.
PMID- 9650298
TI - Genetic characterization of RRS1, a recessive locus in Arabidopsis thaliana that
confers resistance to the bacterial soilborne pathogen Ralstonia solanacearum.
AB - The soilborne, vascular pathogen Ralstonia solanacearum, the causative agent of
bacterial wilt, was shown to infect a range of Arabidopsis thaliana accessions.
The pathogen was capable of infecting the Col-5 accession in an hrp-dependent
manner, following root inoculation. Elevated bacterial population levels were
found in leaves of Col-5, 4 to 5 days after root inoculation by the GMI1000
strain. Bacteria were found predominantly in the xylem vessels and spread
systematically throughout the plant. The Nd-1 accession of A. thaliana was
resistant to the GMI1000 strain of R. solanacearum. Bacterial concentrations
detected in leaves of Nd-1, inoculated with an hrp+ strain of R. solanacearum,
were only slightly higher than those detected in the susceptible accession, Col
5, following inoculation with a strain whose hrp gene cluster was deleted. Leaf
inoculation of the GMI1000 strain on the resistant accession Nd-1 induced the
formation of lesions in the older leaves of the rosette whereas the same strain
of R. solanacearum provoked complete wilting of Col-5. Resistance to strain
GMI1000 of R. solanacearum segregated as a simply inherited recessive trait in a
genetic cross between Col-5 and Nd-1. F9 recombinant inbred lines generated
between these two accessions were used to map a locus, RRS1, that was the major
determinant of resistance between restriction fragment length polymorphism
markers mi83 and mi61 on chromosome V. This region of the A. thaliana genome is
known to contain many other pathogen recognition capabilities.
PMID- 9650299
TI - Role of the Agrobacterium tumefaciens VirD2 protein in T-DNA transfer and
integration.
AB - VirD2 is one of the key Agrobacterium tumefaciens proteins involved in T-DNA
processing and transfer. In addition to its endonuclease domain, VirD2 contains a
bipartite C-terminal nuclear localization sequence (NLS) and a conserved region
called omega that is important for virulence. Previous results from our
laboratory indicated that the C-terminal, bipartite NLS and the omega region are
not essential for nuclear uptake of T-DNA, and further suggested that the omega
domain may be required for efficient integration of T-DNA into the plant genome.
In this study, we took two approaches to investigate the importance of the omega
domain in T-DNA integration. Using the first approach, we constructed a T-DNA
binary vector containing a promoterless gusA-intron gene just inside the right T
DNA border. The expression of beta-glucuronidase (GUS) activity in plant cells
transformed by this T-DNA would indicate that the T-DNA integrated downstream of
a plant promoter. Approximately 0.4% of the tobacco cell clusters infected by a
wild-type A. tumefaciens strain harboring this vector stained blue with 5-bromo-4
chloro-3-indolyl beta-D-glucuronic acid (X-gluc). However, using an omega-mutant
A. tumefaciens strain harboring the same binary vector, we did not detect any
blue staining. Using the second approach, we directly demonstrated that more T
DNA is integrated into high-molecular-weight plant DNA after infection of
Arabidopsis thaliana cells with a wild-type A. tumefaciens strain than with a
strain containing a VirD2 omega deletion/substitution. Taken together, these data
indicate that the VirD2 omega domain is important for efficient T-DNA
integration. To determine whether the use of the T-DNA right border is altered in
those few tumors generated by A. tumefaciens strains harboring the omega
mutation, we analyzed DNA extracted from these tumors. Our data indicate that the
right border was used to integrate the T-DNA in a similar manner regardless of
whether the VirD2 protein encoded by the inciting A. tumefaciens was wild-type or
contained an omega mutation. In addition, a mutant VirD2 protein lacking the
omega domain was as least as active in cleaving a T-DNA border in vitro as was
the wild-type protein. Finally, we investigated the role of various amino acids
of the omega and bipartite NLS domains in the targeting of a GUS-VirD2 fusion
protein to the nucleus of electroporated tobacco protoplasts. Deletion of the
omega domain, or mutation of the 10-amino-acid region between the two components
of the bipartite NLS, had little effect upon the nuclear targeting of the GUS
VirD2 fusion protein. Mutation of both components of the NLS reduced, but did not
eliminate, targeting of the fusion protein to the nucleus.
PMID- 9650300
TI - Identification of an Arabidopsis thaliana mutation (vsm1) that restricts systemic
movement of tobamoviruses.
AB - Following inoculation, many plant viruses spread locally from cell to cell until
they reach the vascular system, through which they then move to other parts of
the plant, resulting in systemic infection. To isolate host genes involved in
systemic transport of plant viruses, ethyl methanesulfonate-mutagenized
Arabidopsis thaliana plants were screened for significant delays in the systemic
movement of turnip vein clearing virus (TCVC). One such mutant, designated vsm1
(virus systemic movement), was identified. Unlike the wild-type plants, vsm1 did
not develop viral disease and did not allow the systemic spread of the virus. The
local viral movement within the inoculated vsm1 leaves, however, was not
affected. TVCV systemic movement within the vsm1 plants was likely blocked at the
step of viral entry into the host plant vasculature from the infected leaf
tissue. vsm1 plants also restricted the systemic movement of another tobamovirus
but not of an unrelated carmovirus.
PMID- 9650301
TI - Use of monoclonal antibodies to determine biomass of Cladosporium fulvum in
infected tomato leaves.
AB - A monoclonal antibody, OX-CH1, was raised against surface washings of
Cladosporium herbarum. This antibody recognizes an epitope that is found in
various fungi belonging to the genus Cladosporium, including C. fulvum, the
causal agent of tomato leaf mold. The epitope is present at comparable levels in
two different races of C. fulvum and in transgenic isolates derived from them.
The epitope is heat-and protease-resistant but sensitive to oxidation with
periodate and it is constitutively expressed in C. fulvum grown in pure culture
and on the plant. C. fulvum can be detected in infected tissues at levels
starting from around 1 mg fresh weight of fungus per g fresh weight of leaf
tissue. Noninfected tomato leaves do not cross-react with OX-CH1. We have
developed an enzyme-linked immunosorbent assay (ELISA) for fungal biomass in
tomato leaves and compared it with the assay based on measurements of beta
glucuronidase (GUS) activity in tissues infected with a transgenic isolate of C.
fulvum race 4 carrying a uidA gene; the two assays give similar results.
PMID- 9650302
TI - Quantification of ammonia in human breath by the selected ion flow tube
analytical method using H30+ and 02+ precursor ions.
AB - We show how our selected ion flow tube mass spectrometric technique for trace gas
analysis can be used to determine the concentrations of ammonia in alveolar
breath from single exhalations using both H30+ and 02+ precursor ions for
chemical ionization. Thus, data are presented of the alveolar ammonia
concentrations in the breath of six healthy volunteers following the ingestion of
a liquid protein meal, which show that consistent values are obtained using these
two precursor ions. Alveolar breath ammonia concentrations (which range from 200
to 1750 ppb in these individuals) are compared with those obtained from bag
samples of breath from the same individuals.
PMID- 9650303
TI - Ion trap mass spectrometry for the characterization of N-methyl-1- (3,4-methylene
dioxyphenyl)-2-butanamine and N-ethyl-3,4- methylenedioxyamphetamine, two widely
distributed street drugs.
AB - The potential of ion trap mass spectrometry has been evaluated for the
characterization and distinction of two isomeric amphetamines drugs, namely N
methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine and N-ethyl-3,4
methylenedioxyamphetamine. Whereas the electron impact spectra of the two
molecules lack specificity, collisional experiments on the ionic species at m/z
72 allows unequivocal distinction between the two isomers. Analogous results are
achieved by positive ion chemical ionization and collisional experiments on the
protonated molecules. All the different approaches have been successfully applied
to the gas chromatography/mass spectrometry analysis of a tablet of illicit drug.
PMID- 9650304
TI - Further considerations on the use of matrix-assisted laser desorption/ionization
mass spectrometry in the analysis of glycated globins.
PMID- 9650306
TI - [Experimental microsurgery of the facial nerve: end-to-end suture versus
approximated ends wrapped with masseter muscle aponeurosis].
AB - As an alternative to end-to-end facial nerve microsurgery, we propose anastomosis
of the sectioned nerve ends and wrapping with ipsilateral masseter fascia. This
intervention was performed on the right facial nerve of 20 Wistar rats and
compared with classical end-to-end anatomosis performed on the left nerve of the
same rats. At the end of the experiment, histological studies were made of each
nerve removed "en bloc" with the ipsilateral lip orbicular muscle. Five micra
thick sections were stained using conventional and immunohistochemical methods.
We analyzed truncal integrity, fibroblast proliferation, demyelination,
lymphocyte proliferation, granulomatous reaction, and muscle degeneration in both
types of anastomosis. The differences between the two types of anastomosis were
statistically non-significant, and both interventions produced similar functional
results. Small differences between the techniques might condition the use of one
or the other in selected cases.
PMID- 9650305
TI - [The effects of aging on the volume of human vestibular nuclei].
AB - Elderly persons often have balance disorders, with dizziness that sometimes leads
to falls. Changes in the peripheral vestibular system with age, with loss of the
hair cells and neurons of Scarpa's nucleus, have been studied for years. However,
the changes in the vestibular nuclear complex with age have not been examined. We
studied paraffin-embedded brainstems from nine persons of different ages in order
to analyze possible changes with age. No abnormalities were observed in the
volume or length of the vestibular nuclei, except for a decrease in both
dimensions in the superior vestibular nucleus (SNV). All the main vestibular
nuclei showed an increase in lipofuscin content with age that seemed to be less
marked in the SNV. The low lipofuscin concentration in the SNV could be related
with the conservation of vestibular reflexes, the center of which seems to be the
SVN, in elderly persons.
PMID- 9650307
TI - [Comparative cephalometric study in patients with obstructive sleep apnea
syndrome (OSAS), simple snorers and controls].
AB - Lateral cranial teleradiography was carried out in 106 subjects, including obese
and non-obese patients with obstructive sleep apnea syndrome (OSAS) and obese and
non-obese healthy snorers and controls. In the OSAS patients alone, the hyoid
bone occupied an abnormally low position, which pushed the tongue into a more
vertical position. OSAS patients had the most voluminous soft tissues, followed
by simple snorers and controls. Soft tissue volume generally was related with
obesity. The pharyngeal airway space was widest in controls, intermediate in
snores and narrowest in OSAS patients, except in the hypopharynx, where airway
dimensions were similar in all the patients studied.
PMID- 9650308
TI - [Surgical treatment of cholesteatoma: are wall-down techniques superior to wall
up techniques? A 50-year-old controversy].
AB - A retrospective study was made of the evolution of our policies in the surgical
treatment of cholesteatoma between 1984 and 1993. An evaluation was made of 103
patients operated by one of the authors [mean age 38 +/- 15 years; 60 (58%) men
and 43 (42%) women]. The mean follow-up was 34 +/- 31 years. Binary logistical
regression was used to analyze our patient series. Two factors that were
associated statistically with the wall-down procedure were the degree of
ossicular chain damage and the integrity of the posterior wall of the external
auditory canal. The frequency of wall-down procedures has increased in our
department.
PMID- 9650309
TI - [study of acoustic trauma in hunters using otoacoustic emission recording].
AB - Transitory otoacoustic emissions (TOAE) were analyzed in 48 ears of male hunters
(age range: 30-45 years: mean age: 37 years) and in a population with normal
hearing. All the ears had TOAE. The incidence of TOAE for the 1, 2, 3, 4, 5 and 6
KHz frequential bands was significantly lower in hunters than in the normal
subjects (p < 0.001). The mean amplitude of TOAE was significantly lower in
hunters (9.2 dB SPL) than in the control group (16 dB SPL; p < 0.001). The
amplitude of the TOAE for the frequencies 1, 2, 3, 4, 5 and 6 KHz was
significantly lower in hunters than in controls (p < 0.001).
PMID- 9650310
TI - [Diagnostic biopsy with paranasal sinus endoscopy].
AB - Rigid endoscopy allows clear visualization of the nasal fossa and paranasal
sinuses and permits biopsies to be obtained under direct vision from relatively
inaccessible sites. In most cases the biopsy can be made using local anesthesia,
but selected patients require general anesthesia. We report the results of 31
patients who underwent biopsy with rigid nasal endoscopy under general
anesthesia. Of the 31 patients, a diagnostic biopsy was achieved in 30 (96.7%).
We define a diagnostic biopsy as one which yielded a histopathological diagnosis
that did not change as a result of clinical findings, examinations or further
biopsies performed during follow-up. We recommend the use of endoscopic nasal
biopsy of nasal and paranasal neoplasms as an easy, safe and reliable technique.
PMID- 9650311
TI - [Overexpression of p53 protein in epidermoid carcinoma of the pyriform sinus].
AB - Mutation of the p53 protein may be the commonest genetic event in the development
of malignant neoplasms in humans. We analyzed the immunohistological expression
of p53 in tissue sections from 51 patients with squamous cell carcinoma of the
pyriform sinus who were treated with surgery and postoperative radiotherapy.
Overexpression of p53 was found in 37 (72.5%) tumors. No correlation was found
between p53 overexpression and clinical and histopathological parameters.
Recurrence and overall survival did not differ between p53-positive and p53
negative cases.
PMID- 9650312
TI - [Prevalence of voice disorders among educational professionals. Factors
contributing to their appearance or their persistence].
AB - A study was made of the prevalence of voice disorders and their risk factors in
teaching professionals of Logrono, Spain. A prevalence and case-control study was
made, including interviews, ENT examination, videostrobolaryngoscopy, perceptual
evaluation of hoarseness, basic aerodynamic tests, the physical range of
phonation, and a physical analysis of the acoustic signal. The prevalence of
voice disorders among Logrono teachers was 17.7% (confidence interval: 12.1-25%).
Nodular lesions (8.1%) were the most frequent pathology, followed by
hyperfunctional dysphonia (4.1%), chronic laryngitis (2.7%), polyps (1.4%),
hypofunctional dysphonia (0.7%), and submucous suffusion (0.7%). Voice disorders
were more prevalent in women (19.3%) than in men (15.6%), and among teachers of
the lowest grades: 36.4% in nursery schools, 25% in elementary school, and 20.8%
in junior school. The width and depth of classrooms, larger number of students,
longer classroom hours, and noise level were related with the frequency of voice
disorders.
PMID- 9650313
TI - [Prognostic value of morphometry and nuclear stereology in laryngeal epidermoid
carcinoma].
AB - BACKGROUND AND METHODS: A series of 70 consecutive patients with laryngeal
carcinoma treated by induction chemotherapy is reported. The prediction of the
response to induction chemotherapy was evaluated by nuclear morphometric and
stereological analysis of the tumor cells. RESULTS: Statistically significant
differences were found in the nuclear form factor (FF, p < 0.021) and nuclear
contour index (NCI, p < 0.017) between the groups of patients with a complete
response (CR), partial response (PR) or no response (NR) to induction
chemotherapy. Comparison of the groups of patients with partial response or
complete response to IC with the group with no response yielded statistically
significant differences in the nuclear form factor (FF, p < 0.002), nuclear
contour index (NCI, p < 0.0032) and nuclear orientation angle (NOA, p < 0.036).
CONCLUSION: Nuclear morphometric analysis of the tumor cells was a useful tool
for predicting response to induction chemotherapy in a significant number of the
patients with laryngeal tumors in our series.
PMID- 9650314
TI - [Laryngeal granular cell tumor].
AB - Granular cell tumors are rare benign neoplasms. Their usual location is in the
head and neck, with the larynx being the most frequent ENT site. Three cases of
granular cell tumor of the larynx are reported and their characteristics are
reviewed.
PMID- 9650315
TI - [Benign paroxysmal vertigo in childhood].
AB - Benign paroxysmal vertigo of childhood is a clinical disorder that usually begins
at age 4. The child's otoneurological examination is normal in the intercrisis
and the brief episodes of true vertigo are typical. In this paper we describe six
new cases that had a follow-up of at least one year after diagnosis. Only a few
of the patients had demonstrated vasomotor migraine, but all the children had a
family history of migraine, which supports the hypothesis that this disorder is a
migraine equivalent. The pathogenesis may be related with a transitory vascular
disturbance that produces ischemia of the vestibular nuclei and pathways, as
occurs in other vascular territories during typical migraine. One longer-than
usual episode is reported. Otherwise, the evolution of this condition is
favorable.
PMID- 9650316
TI - [Invasive giant prolactinoma].
AB - Large prolactin-secreting tumors are rare and their endocrinological and surgical
management may be complex. We report the case of a patient with a prolonged
history of unilateral tinnitus and sensation of a stopped-up ear who had a very
large, invasive and aggressive tumor of the sphenoidal region with bone
destruction, invasion of structures in every direction from the sellar region and
extracranial extension to the ethmoid and nasopharynx. Serum prolactin level at
the time of diagnosis was 16,860 ng/ml (normal: 3-17 ng/ml). Medical treatment
with bromocriptine reduced the prolactin level to 31 ng/ml and reduced the size
of the tumor, although less than expected. The literature is reviewed and the
rarity of such large, invasive prolactinomas is highlighted, as well as the
absence of symptoms and signs suggesting the presence of such a large tumor of
the skull base.
PMID- 9650317
TI - [Malignant pleomorphic adenoma of the palate].
AB - Pleomorphic adenoma or mixed tumor is the most common benign neoplasm of the
minor salivary glands. These tumors rarely have malignant features. Three
varieties are differentiated by histological features and tumor behavior. Whether
malignant tumors develop on benign adenomas or are malignant from onset is still
not known. A malignant mixed tumor of the minor salivary glands of the palate is
reported. The difficulty of histological diagnosis, in spite of
immunohistochemical techniques, is emphasized and the surgical treatment is
described.
PMID- 9650318
TI - [Ethmoid metastasis of primary breast tumor].
AB - Metastatic tumors to the paranasal sinuses are uncommon. Symptoms and imaging
studies are non-specific and usually similar to primary neoplasms in this region.
Histological study of the neoplastic tissue is essential in order to ascertain
its origin. A case of breast adenocarcinoma that metastasized to the ethmoid
sinus is reported and the literature is reviewed.
PMID- 9650319
TI - [Cavernous hemangioma of the maxillary sinus].
AB - A 67-year-old man had an intraosseous giant cavernous hemangioma in maxillary
sinus. We describe the MRI features of the case and note the potential risk of
performing office biopsies on such lesions. Our patient did not have profuse
hemorrhage and preventive measures were taken.
PMID- 9650320
TI - [Postsurgical hyponatremia].
AB - Hyponatremia is a relatively common postoperative complication which sometimes
has dramatic consequences. A case of severe hyponatremia is reported. Although
unrelated with the surgical technique, this complication is potentially life
threatening.
PMID- 9650321
TI - [Laparoscopic feeding gastrostomy: an alternative to the nasogastric tube].
AB - Dysphagia is common in head and neck cancer and feeding becomes difficult.
Nasogastric tubes cannot by placed in some patients and are poorly tolerated in
others. However, endoscopic laparotomy techniques have advanced to a point in
which they allow feeding gastrostomies to be used, which are non-aggressive, well
tolerated and a satisfactory alternative for patients with contraindications for
upper endoscopy.
PMID- 9650322
TI - [Facial paralysis after non-otologic surgery under general anesthesia].
AB - Peripheral facial palsy is rare after non-otological surgery under general
anesthesia. The condition generally is attributed to damage produced by
endotracheal intubation maneuvers in patients with anatomic variants of the
facial nerve. We report three cases of facial palsy which occurred after
abdominal surgery. In every case, nitrous oxide gas was used in anesthesia. One
patient had intubation via tracheostomy; all the patients had endocranial facial
symptoms and a history of previous surgery. The diversity of these factors
suggests that other mechanisms of production aside from damage produced by
endotracheal intubation should be considered. The use of nitrous oxide increases
middle ear pressure and could produce focal nerve compression. This does not
invalidate earlier hypotheses, but does clarify pathophysiological concepts of
this condition.
PMID- 9650323
TI - Are case reports obsolete?
PMID- 9650324
TI - Effects of colchicine and colchiceine in a biochemical model of liver injury and
fibrosis.
AB - BACKGROUND: The accumulation of collagen is a salient feature of chronic liver
injury. The objective of this study was to investigate and compare the
therapeutic effectiveness of colchicine and one of its metabolites, colchiceine,
to protect rats from developing liver injury and fibrosis. METHODS: To accomplish
this, the authors used a procedure developed by others to produce liver injury
and fibrosis by chronic administration of CCl4 in rats. The effect of both
compounds on collagen metabolism and liver injury was analyzed. RESULTS: Although
both compounds prevented increase in collagen synthesis, animals treated with
colchicine did not show a reduction in collagen content compared with animals
treated with CCl4. On the other hand, the animals treated with colchiceine along
with CCl4 showed a 50% reduction in hepatic collagen content as well as an
improvement in histological architecture. Both compounds, colchicine and
colchiceine, increased the intracellular degradation of collagen in addition to
increasing collagenase activity as compared to non-treated rats. However,
collagenase activity was lower in animals treated with colchicine and colchiceine
than in the fibrotic livers treated with CCl4. The changes in collagen metabolism
correlated with changes in parameters of liver injury. CONCLUSIONS: In
conclusion, the compound colchiceine may be recommended in the treatment of
chronic liver diseases rather than its precursor, colchicine, due to the fact
that it showed a lower accumulation of collagen content and has a better anti
fibrogenic effect than does colchicine.
PMID- 9650325
TI - Progesterone: protective effects on the cat hippocampal neuronal damage due to
acute global cerebral ischemia.
AB - BACKGROUND: Barbiturates, benzodiazepines, and synthetic steroids having
anesthetic properties, by enhancing the inhibitory GABAergic neurotransmission to
the neuronal circuits of cerebral structures vulnerable to ischemia, reduce the
damage induced by this condition. Some endogenous steroids resulting from
progesterone (P4) biotransformation in the brain exert GABAergic effects, thus
inhibiting neuronal excitability. Hence, P4 administration both before and after
an experimentally induced ischemic episode may prevent or decrease the ischemic
cerebral damage. METHODS: Ovariectomized adult cats were treated s.c. with either
P4 (10 mg/kg/day) or corn oil during 7 days before and 7 days after being
subjected to a period of acute global cerebral ischemia by 15 min of
cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of
survival, animals were sacrificed and the brains perfused in situ and formalin
fixed for histological examination. RESULTS: Acute global cerebral ischemia
resulted in a severe loss of neurons (54-85%), mainly in CA1 and CA2 subfields of
oil-treated cats. Progesterone significantly reduced the neuronal loss in those
areas (21-49%). CONCLUSIONS: Overall results suggest that progesterone exerts
protective effects against the neuronal cerebral damage induced by acute global
cerebral ischemia.
PMID- 9650326
TI - The hindlimb hyperextension associated to the urogenital response in newborn
underfed rats.
AB - BACKGROUND: The aim of the study was to investigate how neonatal undernutrition
interacts with mother-infant relationships to interfere with the expression of
the urogenital response in the newborn. METHODS: The hyperextensive reflex
components associated to the urogenital response (HUR) were measured between
postnatal days 1-21, in control and neonatally undernourished rats with or
without fullness of the bladder. RESULTS: In Experiment 1, both male and female
underfed rats with different degrees of bladder fullness exhibited an increment
in HUR latency and vertical hindlimb displacement, reduced transversal separation
and prolonged performance of hindlimb relaxation. Experiment 2 was performed in
rats after urine elicitation provoked only reduced hindlimb transversal
separation in males, and prolonged latency to HUR in females. DISCUSSION: These
findings may be related to the vulnerability to neonatal undernutrition of the
maturational processes which take place in the spinal cord, the condition of the
bladder, and hindleg muscle maturation during this period of life. CONCLUSIONS:
Data suggest that neonatal undernutrition may play a role in mother-infant
interaction by interfering with HUR responses to maternal anogenital licking of
the pups.
PMID- 9650327
TI - Biotypes and serotypes of Haemophilus influenzae of clinical isolates from
Mexican children.
AB - BACKGROUND: Infectious diseases caused by H. influenzae type b are considered
preventable through vaccination with Hib conjugate vaccines. Some countries which
follow Hib vaccination programs are close to eradication of the disease. In
Mexico in particular, little epidemiological information is available. METHODS:
In this study, 90 clinical strains of H. influenzae were obtained from Mexican
children who were treated in four pediatric hospitals in Puebla City, and were
diagnosed with invasive or localized infectious diseases. The strains were
identified by standard bacteriological methods. Biotyping was done by Kilian
criteria and serotyping by coagglutination. RESULTS: H. influenzae infections
were found in children younger than 5 years of age, and 68.8% of the children
were younger than 24 months. Sixty percent of the isolates belonged to serotype
b, 31.1% were nontypeable, and 7.7% were considered non-type b. Serotype b was
the most frequent isolate associated with invasive infectious diseases; however,
nontypeable strains were isolated more frequently from children with otitis,
sinusitis, conjunctivitis, and bronchial secretion. Non-type b serotypes were
isolated from invasive and non-invasive infections in few cases. Biotypes I and
IV were the most frequent isolates of H. influenzae. CONCLUSIONS: This study
emphasizes the urgent need for an Hib-conjugated vaccine to achieve immunization
in a pediatric population.
PMID- 9650328
TI - Lowering glycemic index of food by acarbose and Plantago psyllium mucilage.
AB - BACKGROUND: A study was designed to evaluate the effect of acarbose and Plantago
psyllium mucilage on glycemic index (GI) of bread. METHODS: Twelve patients with
non-insulin-dependent diabetes mellitus (NIDDM) and ten healthy volunteers were
studied. Three meal tests with an intake of 90 g of white bread (50 g of
carbohydrates) were performed on each subject. In one test, 200 mg of acarbose
was given, while 15 g of P. psyllium mucilage was given in another test, and only
bread was ingested in the control test. Serum glucose and insulin concentrations
were measured every 30 min from 0-180 min. Net area under curve (AUC)
concentrations of glucose and insulin, GI and insulinic index were calculated.
RESULTS: In NIDDM patients, AUC-glucose in the test with acarbose (1.9 +/- 0.7
mmol/L) and with P. psyllium (4.3 +/- 1.2 mmol/L) were significantly lower than
in the control test (7.4 +/- 1.5 mmol/L) (p < 0.01). GI of bread plus acarbose
was 26 +/- 13, and of bread plus P. psyllium, 59 +/- 10 (p < 0.05). AUC-insulin
and insulinic index behave similarly. In healthy individuals, AUC-glucose and GI
did not significantly change with the treatments; however, insulinic index with
acarbose was 17 +/- 16, and with P. psyllium was 68 +/- 15 (p < 0.05). Acarbose
or P. psyllium decreased GI of bread in NIDDM patients and diminished insulinic
index in NIDDM and in healthy subjects. CONCLUSIONS: Adding acarbose or P.
psyllium to meals may reduce glycemic index of carbohydrate foods and may help
diabetic control.
PMID- 9650329
TI - Recognition of Streptococcus pyogenes and skin autoantigens in guttate psoriasis.
AB - BACKGROUND: Guttate psoriasis is associated with infections by Streptococcus
pyogenes and cross-reactions between skin and streptococcal antigens have been
reported, suggesting an autoimmune component in the disease. METHODS: In this
work, the authors looked for antibodies against S. pyogenes M-5 antigens by
immunoblot in 52 sera of psoriasis patients and in 52 sera of normal individuals.
Histological and immunohistochemical analysis in skin biopsies from lesions of
another group of 16 clinically diagnosed guttate psoriasis patients and four
healthy controls were also carried out. RESULTS: All guttate psoriasis patients
studied (11) had IgG antibodies that intensively recognized three different
proteins of 70, 60 and 14 kDa, as compared to sera from patients with other forms
of psoriasis or from healthy controls. The diagnosis of psoriasis was confirmed
in 14 of the patients by hematoxylineosin staining. Of the other two patients,
one was diagnosed as parapsoriasis and the other as liquen. By indirect
immunofluorescence (IFI), all 14 psoriatic patients had autoantibodies against
their own lesional skin that did not recognize normal skin from control subjects
or from the two non-psoriatic patients. The parapsoriatic and the liquen patients
did not have autoantibodies. A rabbit immune serum against S. pyogenes antigens
reacted with lesional skin from the 14 guttate psoriatic patients, but not with
normal skin from controls or with lesional skin from the 2 non-psoriatic
patients. CONCLUSIONS: The recognition by immunoblot of streptococcal antigens by
serum of guttate psoriasis patients, the presence of autoantibodies against their
own skin, and recognition of the same skin antigens by anti-streptococcal rabbit
antibodies confirm the participation of the immune system and of streptococcal
infections in guttate psoriasis.
PMID- 9650330
TI - Studies on nap sleep in young students. Relationships between polygraphic data
and the occurrence of dreams in replacing naps.
AB - BACKGROUND: Afternoon nap sleep was studied in 32 young male medical students who
take customary naps to replace loss in nocturnal sleep. METHODS: From 16
subjects, a group called dreamers was formed, and the other 16 individuals were
grouped as non-dreamers. Polygraphic recordings lasting 30 min were done at a
fixed time in the afternoon, and the relationship between these data and the
occurrence of dreams was investigated. RESULTS: We found that this replacing of
nap sleep can adopt different sequences and relative durations of its phases, and
can also show individual variations that have a systematic relationship with the
occurrence of dreams. It was observed that dreaming was closely related to the
appearance, during the first 10 minutes of the nap, of Stage I with Slow Eye
Movements, interrupted by Sleep Onset REM Periods (SOREMPs) and, to a lesser
degree, to phases IV and III of slow sleep. CONCLUSIONS: According to these
findings, the existence of dreamers and non-dreamers depends upon the
relationship between an internal sleep-waking rhythm, and an external rhythm
imposed by the daytime resting-activity schedule on the habit of dreaming, and,
to a certain extent, on the mental phenomena occurring between the generation of
dreams and the moment of awakening.
PMID- 9650331
TI - Prognostic significance of cutaneous depigmentation in Mexican patients with
malignant melanoma.
AB - BACKGROUND: The clinical significance of cutaneous depigmentary phenomena in
patients with malignant melanoma is not clear. There are two varieties: 1)
vitiligo (VIT), and 2) leukoderma acquisitum centrifugum (LAC). METHODS: In order
to evaluate the outcome of our patients with malignant melanoma and skin
depigmentation (VIT or LAC), the patients in this study with this association
were retrospectively reviewed and compared with the total melanoma patients at
the Oncology Hospital and the XXI Century National Medical Center of the Mexican
Social Security Institute in Mexico City. RESULTS: Nine cases were found from
1985-1995. There were eight women and one man, their mean age was 63 years. Six
melanomas were located in the foot, one in the leg, one in the anus and one in
the neck. All were Clark's levels III, IV or V, and their mean tumor thickness
was 5.7 mm. Four out of nine patients had regional lymph node metastasis. Six
melanomas were associated with VIT and three with LAC. Three patients developed
the depigmentation after chemo- or chemoimmunotherapy. All nine patients are
alive (100%) with a mean follow-up of 55 months (9-141), eight out of nine have
no evidence of tumor. CONCLUSIONS: From these data it may be concluded that the
study patients with malignant melanoma and VIT or LAC have a higher-than-expected
survival according to their prognostic factors. Therefore, the presence of the
depigmentation phenomena must be looked for intentionally.
PMID- 9650332
TI - Immediate results of the Inoue mitral valvotomy in patients with previous
surgical mitral commissurotomy. Preliminary report.
AB - BACKGROUND: The objective of this study is to evaluate the immediate result of
the percutaneous mitral valvotomy in patients with previous surgical mitral
commissurotomy, compared with patients considered ideal for the performance of
the procedure. METHODS: The authors of this paper compared the immediate results
of the percutaneous mitral valvotomy (PMV) performed on two groups of patients.
Group I included 20 patients who were good candidates for PMV, with an
echocardiographic score of < or = 8, without evidence of left atrial thrombus,
and with no recent embolic event. Group II included seven patients with previous
mitral commissurotomy (MC). RESULTS: According to the Wilcoxon non-parametric t
test analysis, the hemodynamic variables changed significantly in the patients of
group I: the mitral area increased from 1.21 +/- 0.41 to 2.62 +/- 0.75 cm2 (P = <
0.001); the mean left atrial pressure decreased from 17.2 +/- 7.2 mmHg to 9.2 +/-
4.5 mmHg (P = < 0.001), and the pressure transmitral gradient decreased 12.4 +/-
6.8 to 3.3 +/- 1.26 mmHg (P = < 0.001). No statistically significant difference
in the hemodynamic changes of the patients of group II after the PMV was found:
the mitral area increased from 1.2 +/- 0.2353 to 1.96 +/- 0.57 cm2; the mean left
atrial pressure decreased from 17.42 +/- 10.35 to 12.42 +/- 7.3 mmHg, and the
pressure mitral gradient decreased from 11.47 +/- 6.5 to 5.7 +/- 4.8 mmHg. The
mitral area determined by echocardiographic procedure showed the same tendency in
patients with previous MC. CONCLUSIONS: In spite of this tendency, during the
follow-up after PMV the NYHA functional class decreased from II-IV to I in the
patients with previous MC. Because a second surgical MC results in higher
mortality, PMV is indicated in patients with previous MC, delaying or avoiding a
second MC or valve replacement.
PMID- 9650333
TI - Maternal mortality regionalization and trend in Mexico (1937-1995)
AB - BACKGROUND: The objectives were to establish regions by level of maternal
mortality in order to evaluate its trend from 1937-1995 and to analyze
characteristics of cases which occurred from 1990-1995. METHODS: Regionalization
of the country by maternal mortality level was carried out using Poisson
regression. Level and mortality trends were analyzed globally and compared by
regions using Poisson and linear regression. Characteristics of cases were
analyzed from 1990-1995 using proportions and X2 test. RESULTS: Four well
differentiated and independent regions were established. Low and medium maternal
mortality rate regions were found in northern and northwestern Mexico. High and
very high maternal mortality regions were found in the South and the Southeast of
the country. Even when maternal mortality had descended, the speed of the descent
has decreased and in the last few years, maternal mortality has increased. The
quality of health care is a challenge for regions with low mortality rates, while
the problem of accessibility is present in those with very high mortality rates.
CONCLUSION: The employment of this regionalization approach in maternal mortality
analysis would be useful to determine specific problems for each region. The
establishment of programs according to this analysis could contribute to decrease
in maternal mortality cases in Mexico.
PMID- 9650334
TI - Risk factors of stroke at high and low altitude areas in Saudi Arabia.
AB - BACKGROUND: The epidemiology of stroke at different geographical locations in the
Kingdom of Saudi Arabia has not been adequately investigated. METHODS: In this
study, clinical types and risk factors of stroke were compared among patients at
low-altitude (Riyadh, 620 m) and high-altitude (Al Baha > 2000 m) areas using a
case-control study design. One-hundred ninety recently diagnosed cases (109 from
Riyadh and 81 from Al Baha) were verified and subjects were interviewed. An equal
number of age- and sex-matched controls from the corresponding areas were also
interviewed using a specific standard questionnaire. RESULTS: The frequency of
thrombotic stroke at high altitude was 93.4% as compared to 79.3% at low altitude
(P < 0.05). The odds ratios (OR) for the different risk factors at high and low
altitudes, respectively, were: hypertension 4.4 and 2.1; diabetes mellitus: 2.7
and 1.9; ischemic heart disease (IHD): 2.4 and 1.9; atrial fibrillation: 3.9 and
3.3, and smoking: 2.3 and 2.5. The mean hematocrit values were 45.3% at high
altitude and 41.0% for low altitude patients (P < 0.001) and its association with
stroke at high altitude remained significant even after adjusting for age, gender
and occupation. CONCLUSIONS: The study's finding of an increased frequency of
thrombotic stroke at high altitude was explained by increased hematocrit which
might have caused this in conjunction with other factors such as hypertension and
IHD. Larger studies are recommended for better clarification of interaction
between high altitude and other established risk factors not included in this
study, such as sickle cell anemia and congenital heart diseases in young
patients.
PMID- 9650335
TI - Risk factors for amputation in diabetic patients: a case-control study.
AB - BACKGROUND: The objective was to quantify risk factors for lower extremity
amputation in patients with diabetes mellitus in an attempt to prevent
amputation. METHODS: This investigation was conducted as a case control study
among diabetic males from 30-90 years of age with an average clinical duration of
diabetes of 10 years: included were 80 cases which required a supracondyle
amputation associated with diabetes mellitus, and 240 controls without injuries
in the lower extremities. Measurements included the following: socioeconomic
level, psychosocial risk factors, neuropathics, peripheral vascular factors, high
blood pressure, smoking; environmental factors, health care, self care, and
nutritional and metabolic factors in patients with diabetes mellitus before
surgery. Statistically significant risk factors identified from analyses were:
absence of lower leg vibratory perception (odds ratio = 14.9, 95% CI: 8.2-27.9);
peripheral vascular disease (OR = 8.9, 95% CI: 5.3-15.9); high blood cholesterol
> 450 mg (OR = 3.8, 95% CI: 2.9-8.6); low blood albumin < 3.5 g (OR = 7.9, 95%
CI: 4.8-14.9); hyperurea blood nitrogen > 3.5 mg (OR = 3.1, 95% CI: 1.7-4.9);
obesity (OR = 4.2, 95% CI: 1.51-9.8); time of evolution of diabetes mellitus > 10
years (OR = 3.47, 95% CI: 1.40-8.56); cracks in feet (OR = 3.45, 95% CI: 1.33
8.82); feet soaked in water (OR = 1.8, 95% CI: 1.07-2.93); ingrown toenails (OR =
2.0, 95% CI: 0.6-5.3), and lack of outpatient diabetes education (OR = 3.2, 95%
CI: 1.5-6.7). CONCLUSIONS: Different risk factors for lower extremity amputation
in diabetes mellitus patients were quantified, identifying certain aspects of
preventive impact (patient education, glycemic control, careful daily foot
hygiene, and appropriate footwear) which may be applicable in environmental
factors and which have the possibility of success in lowering the rate of risk
for lower extremity amputation.
PMID- 9650336
TI - Localization of intranuclear RNA by electron microscopy in situ hybridization
using a genomic DNA probe.
AB - BACKGROUND: The presence of RNA in the cell nucleus is well known. However, a
high resolution in situ hybridization evidence for the presence of RNA in some
nuclear particles is still lacking. The aim of this work is to localize RNA in
subnuclear particles using a novel ultrastructural in situ hybridization
procedure. In this study, biotinylated genomic mouse DNA as a probe to localize
total RNA in the nuclei of mouse hepatocytes was used. METHODS: The procedure is
based on paraformaldehyde fixation and embedding in lowicryl resin. Thin sections
are mounted in formvar-coated gold grids. Hybridization is performed on non
denatured thin sections. DNA-RNA hybrids are detected with streptavidin-10 nm
gold particles complex. By controlling the time of nick-translation during
incorporation of biotin into the probe, labeling in the fibrillar portions of the
nucleoplasm is obtained. More digested probes generate more labeling in the
granular components. Nucleoli were similarly labeled. RESULTS: As expected, no
label was observed in the compact chromatin clumps. These results indicate that
granular components as perichromatin granules in the nucleus contain more
processed RNA than fibrillar portions. As a comparison, viral DNA sequences on
denatured RNase-treated thin sections of adenovirus-2 (Ad-2)-infected human cells
were detected. As previously reported, at late stages DNA was observed in the
viral particles and surrounding nucleoplasm, where Ad-2 DNA is synthesized.
CONCLUSIONS: The present procedure allows the study of intranuclear RNA
distribution and will be useful for the analysis of RNA processing in several
types of cells.
PMID- 9650337
TI - Antimicrobial compounds detected in Bocconia arborea extracts by a direct
bioautographic method.
AB - BACKGROUND: Among the numerous in vitro methods for studying the antimicrobial
activity of plant drugs, bioautography has found widespread applications,
especially for the detection of new compounds in complex plant extracts. METHODS:
This paper describes the results obtained during the application of the
bioautographic method to detect antimicrobial compounds in a chloroformic extract
of leaves and stems of Bocconia arborea, a plant used profusely in traditional
medicine for the treatment of diverse infectious diseases. RESULTS AND
CONCLUSIONS: The methods allows for the detection of spots of growth inhibition
of cultures directly in the extract thin layer chromatographic plate previously
dispersed with a broth culture containing the microorganisms. The procedure also
allowed for the detection of the presence of several products in the B. arborea
extract with considerable activity against five different microorganisms.
Additionally, the method allowed the determination that the antimicrobial
activity is due to compounds of probable alkaloid origin.
PMID- 9650338
TI - Chagas disease. First congenital case report.
AB - This is the first report of a congenitally transmitted case of Chagas disease
occurring in Mexico, in a febrile premature newborn girl with low birth weight,
hepatosplenomegaly and pneumonitis. Trypanosoma cruzi blood infection was
detected using both direct smears and concentrated blood preparations. The
patient's mother had a positive serological reaction by two techniques for anti
T. Cruzi antibodies. Two years after anti-chagastic treatment, the child has had
a normal evolution, her serology is negative, and no abnormalities have been
detected by electrocardiography.
PMID- 9650339
TI - [650th anniversary of the founding of Charles University. Six- and-one-half
centuries of medical education in Prague].
PMID- 9650340
TI - [Endocrinology 1996-1997].
AB - Post-traumatic stress-induced disorders are still the focus of interest and most
recently discussions are under way whether stress-induced cortisol excess leads
to atrophy of the brain. In investigation on carcinogenesis the first reports
were published on the use of antisense-oligonucleotides during inhibition of the
development of tumours by a humoral mechanism and on the gene-based
neuroendocrine differentiation of the lungs, perhaps associated with the basis
for the development of small cell carcinoma. The oncogenic action of superoxides
has also humoral mediators. Interest in nitrogen oxide is focused on two areas:
inflammations and hypertension. Intraluminal NO concentrations increase in asthma
2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in
asthma offer new drugs--inhibitors of the development or action of leucotrienes.
The basal NO production is reduced in "essential" hypertension but it is not
known whether it is the cause or consequence. IGF-I increases the formation of NO
in the vascular wall and thus perhaps reduces vascular contractility. As far as
IGF is concerned, it is obvious that if recombinant preparations will be
available, they will be tested in amyotrophic lateral sclerosis, myotonic
dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal
failure and to promote wound healing. STH may also prove useful in cardiac
failure, in particular in cardiac cachexia. That TRH has receptors in the gut is
not surprising, it acts, however, even there via TSH. Thrombopoietin is being
tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin
secretion declines new erythrocytes disappear and only old ones remain in the
blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium
balance.
PMID- 9650341
TI - [Fluorine in the prevention of dental caries].
AB - Classical epidemiological trials which were implemented in localities with a
natural fluoride concentration in drinking water provided evidence that a
concentration of 1 mg per 1 litre of water ensures on optimal preventive effect
as regards dental caries and has no adverse effects on the health status of the
population. In 1945 fluoride supplementation of drinking water was started in the
USA, then in Canada, Chile, Brazil, New Zealand. Based on experience of overseas
countries, this type of prevention of dental caries was started also in European
countries. In the Czech Republic fluoridation of drinking water introduced in
1958 in Tabor and in the course of 25 years it was introduced in 567 localities.
Control examinations in these localities provided evidence of a reduction of
caries experience on average by 40-50% in deciduous as well as permanent
dentition. Despite clearly proved advantages, fluoride prevention has adversaries
who are motivated emotionally or politically and their views are not consistent
with health authorities. In the Czech Republic fluoridation of drinking water was
discontinued in 1988 in Prague and from 1993 in the whole Republic
Discontinuation of fluoridation led to an alarming situation in particular in
preschool children where caries experience and the percentage of children with
intact teeth reached the level recorded twenty years ago.
PMID- 9650342
TI - [Analysis of mortality trends in the West Bohemian Region in comparison with the
entire Czech Republic 1988-1995].
AB - BACKGROUND: Unfavourable trends in Czech republic (CR) started in the sixties and
peaked in the late eighties i.e. in years when a dramatic mortality fall was
observed in most western european countries. So, CR belonged among those Eastern
European countries in that total and cardiovascular mortality showed increasing
and alarming trends. West Bohemia Region (WB) was characterised by the
concentration of heavy industry and high environmental pollution. Because of its
geographical position on the western frontier, it was generally restricted in
capital investment in the past. We wondered whether these phenomenon were
reflected in higher mortality rates than in the rest of CR and which changes
occurred after the year 1989. METHODS AND RESULTS: We compared the age
standardized mortality data from 1988, 91, 93 and 95 in CR and WB for total
mortality, cardiovascular mortality, coronary heart disease, strokes,
malignancies and respiratory diseases. Data were age-adjusted for "World
Population Standards" and rates were given for 100,000 inhabitants. In the whole
CR a significant decrease of total, cardiovascular and cancer mortality was
observed from 1988 to 1995. In WB these trends were similar, however in
comparison to the whole CR the mortality rates remained in each respective period
higher for total, cancer (mainly lung cancer) mortality and for non specific
respiratory disease. In contrast, the coronary mortality rates in CR and WB were
similar, however in WB after a temporary decrease in 1993 a significant increase
in 1995 was observed. On the other hand the stroke mortality rates which were
until 1993 in WB higher, significantly decreased in 1995 below the rates for CR.
The cause of higher mortality rates in WB are far from being clear. To elucidate
this observation epidemiologic studies of environmental pollution, life style of
the population and socioeconomic factors are necessary, even as a further
monitoring of regional mortality rates and trends.
PMID- 9650343
TI - [Surgical treatment of bronchogenic carcinoma. Long-term results in 496 surgical
patients].
AB - BACKGROUND: The operability of lung cancer and the period of survival after
resection of the lungs in our country does not yet attain the standard recorded
in some advanced countries. The objective of the present work is to analyze
factors which influence the survival period after resection therapy of lung
cancer. METHODS AND RESULTS: In 1985-90 in our department 496 patients were
operated on account of lung cancer. This number comprised 31 patients subjected
to explorative thoracototomy and three patients with pulmonary resection on
account of a stage IIIb (pTNM) tumour who were excluded from the statistical
analysis. The retrospective study proper analyzes the results of 462 patients
(403 men and 59 women) operated in stages I, II and IIIa. Their mean age was 57
years (range 30-74 years, SD 7.5 years). The most frequent histological type was
epidermoid carcinoma (68.8%), adenocarcinoma 18.2%, small-cell tumours 5.4% (25
patients). In 262 patients operated on account of lung cancer in stage I (pTNM)
the probability of five-year survival was 49.2%, in patients in stage II 42.1%,
in 158 patients in stage IIIa 20.9% (for all histological types combined). In 437
patients after resection of the lungs on account of non-small-cellular carcinoma
the probability of five-year survival was as follows: stage I 50.0%, stage II
45.0%, stage IIIa 21.2%. CONCLUSIONS: The probability of five-year survival for
the whole group of 462 patients in stages I, II and IIIa was 38.8%. The most
important factor which influenced the probability of five-year survival was the
stage of the disease. Neither age nor sex of the patients nor the histological
type of the tumour had a statistically significant effect on the probability of
five-year survival.
PMID- 9650344
TI - [Calcium channel blockers in the treatment of hypertension and ischemic coronary
disease. Conflicts in their evaluation].
AB - Calcium channel blockers represent a pharmacologically non homogenic group.
Verapamil and diltiazem have myocardial component of their effect, which acts
against activated sympathicus. Short acting dihydropyridines (nifedipin) appear
to be harmful by patients after myocardial infarction which is caused by the
reflex sympathetic response to the predominant vasodilation. In the treatment of
cardiovascular disease (e.g. hypertension, coronary vascular disease) are short
acting dihydropyridines not recommended. Dihydropyridines of the new generation
(amlodipin, felodipin, isradipin, lacidipin, nicardipin, nimodipin, nisoldipin,
nitrendipin) induce less tachycardia due to their favorable kinetic features. If
the slow movement in blood or at the receptor site is not a result of molecule
features there is necessary to use retarded preparations of active substance.
Nevertheless, commonly used retarded preparations fulfil this requirement only
incompletely. The desirable quality is provided by modern form of retardation.
(e.g. GITS) only.
PMID- 9650345
TI - [Transmissible spongiform encephalopathy].
AB - Transmissible spongiform encephalopaties (TSE) are a group of rare fatal diseases
of humans and animals. Prions, small infectious proteinaceous particles, are
their supposed cause. Prusiner's theory (Nobel price 1997) proves that
pathogenetically active prions are conformated physiological prions but problems
of pathogenesis of TSE are still open. Most important representative of human TSE
is Creutzfeldt-Jakob's disease (CJD), that of animal TES is bovine spongiform
encephalopathy (BSE). It seems that a new variant of CJD found in more than 14
young people in the UK is in reality human BSE. Whether it means start of an
epidemy of human BSE is not known.
PMID- 9650346
TI - [Advances in the diagnosis and treatment of neuroblastoma].
AB - Neuroblastoma is the second most common solid tumor in children. The prognosis is
poor for approximately 70% of patients who have widespread disease at the time of
diagnosis. The use of new strategies for classification and therapy has raised
expectations for cure in advanced neuroblastoma. We summarise results and
experiences reached during the last decade.
PMID- 9650347
TI - [Prevalence of osteoporosis in the Czech Republic].
AB - BACKGROUND: The objective of this study was to evaluate the prevalence of
osteoporosis and osteopenia in Czech women and men aged 50 to 75 years. METHODS
AND RESULTS: Bone mineral density was assessed in an age-stratified random sample
of 713 women and 429 men from two cities (Prague and Litomerice) in the lumbar
spine, proximal femur and total body by dual X-ray absorptiometry and in the
distal forearm by single X-ray absorptiometry. The proportion of women and men in
each age group with bone density below specified levels at any of these skeletal
sites was projected to the population structure of the Czech Republic. With
advancing age, in women at 55 years and in men at 65 years of age the population
with normal bone mineral density becomes smaller, and a greater proportion has
osteopenia or osteoporosis. Overall, an estimated 428,000 women and 195,000 men
over age 50 have osteoporosis and another 680,000 women and 435,000 men have
osteopenia. CONCLUSIONS: The results of this first population-based cross
sectional study in the Czech Republic document a high prevalence of osteoporosis
and osteopenia which is comparable with that published for the Netherlands and
the United States. The results offer a basis for economical considerations in
diagnosis, treatment and consequences of osteoporosis.
PMID- 9650348
TI - [Trace elements in biological materials. Preanalysis safeguards].
AB - In order to obtain objective information from estimations of trace elements (Al,
As, Cd, Cr, Co, Cu, Pb, Li, Mn, Hg, Ni, Se, Zn) on deficiency or intake beyond
the toxic limit it is necessary to pay attention among others also to
preanalytical safeguarding, i.e. obtain all relevant information on the patient,
ensure proper selection of material and sampling time, proper sampling and
safeguarding the sample before the estimation proper. If the above rules and
principles are respected, possible significant distortion on the results, which
can be caused e.g. by contamination of the sample, can be prevented.
PMID- 9650349
TI - The legacy of the Nuremberg Code.
PMID- 9650350
TI - [Diuretics in the treatment of hypertension].
AB - Diuretics belong into the group of basic antihypertensive drugs. A number of
clinical trials provided evidence that long-term administration of diuretics
leads not only to effective control of hypertension but has at the same time a
favourable impact on cardiovascular morbidity and mortality. Along with beta
blockers diuretics are recommended as drugs of first choice in patients with
arterial hypertension. The author presents a brief account of different groups of
diuretics incl. their indications.
PMID- 9650351
TI - [Comment on the article by Z. Skodova et al: Decrease in cardiovascular disease
mortality in the Czech Republic 1984-1993 and its causes].
PMID- 9650352
TI - [Nitric oxide--its effects and significance in the human body].
AB - Nitric oxide is a reactive gas with series of important functions in human body.
An important deal of nitric oxide in the etiology and pathogenesis of series of
autoimmune diseases, degenerative diseases of central nervous system etc. is
suggested. This article summarizes the current knowledge about NO mean in
medicine with impact to a perspective possibility of influence of any diseases by
modulation of nitric oxide synthesis.
PMID- 9650353
TI - [A new generation of dressings in the treatment of leg ulcers].
AB - Current methods of topical treatment of leg ulcers are reviewed. Leg ulcers are
chronic wounds in a trophically altered tissue that affects the healing capacity.
Complete healing requires prolonged and rather expensive treatment and the
patient is often disabled during this period. The conventional methods of
treatment of leg ulcers, including various compresses, ointments, pastes and
other topical drugs, that may possess a considerable sensitizing potential, are
to an increasing extent replaced by updated therapy consisting in the use of a
new generation of dressings. The latter include a number of materials that have
been developed on the basis of recent knowledge of wound healing, such as
hydrogels, hydrocolloids, xerogels, hydropolymer dressings, polyurethane foam
sheets, alginate dressings, and non-adherent, non-woven cloth impregnated with
silver and activated charcoal. The selection of the available materials must
depend on the character and stage of the healing process. Each group of dressings
exerts specific effects and none of them can recommended generally for the
treatment of any types of ulceration. A brief survey of indications is given for
each group to avoid their abuse.
PMID- 9650354
TI - [Interleukin-6, tumor necrosis factor alpha and their soluble receptors in Bence
Jones nephropathy. Possible role in pathogenesis andthe importance in the
determination of prognosis in renal insufficiency].
AB - BACKGROUND: Bence-Jones nephropathy, the most serious form of which is renal
failure, is one of the frequent complications in multiple myeloma (MM). Precise
pathogenetic mechanism of renal injury remains unclear. Experimental study points
to the possible role of some cytokines in the development of this type of
nephropathy. We have investigated the levels of interleukin-6 (IL-6), tumour
nekrosis factor alpha (TNF-alpha) and their soluble receptors in patients with
plasmocytoma. METHODS AND RESULTS: The group comprised 49 patients with
plasmocytoma, mostly with MM. Significantly higher levels of IL-6 were found in
patients with irreversible renal insufficiency and/or failure (group A-median
13.3 pg/ml, range 3.6-33.3) comparing patients with reversible impairment (group
B-median 3.1-range 1.8-38.4) (p < 0.01) and those with normal renal functions
(group C-median 2.3-range 0.97-7.41) (p < 0.01). Significant difference was also
found between the groups B and C (p < 0.05). Analysis of variance with the use of
various factors showed that the correlation between IL-6 and prognosis of renal
disease was stronger (p < 0.001) than the correlation between cytokine levels and
the clinical phase of MM (p < 0.05). The difference of IL-6 levels between
various clinical stages of MM was not significant. The levels of sIL-6R were
significantly increased in patients with both reversible and irreversible renal
insufficiency comparing the group with unaffected renal functions (p < 0.05 and p
< 0.01 respectively). TNF-alpha levels did not differ between all 3 groups of
patients, however, significantly increased values of sTNF-R II were observed in
group A vs B and group B vs C (p < 0.05). CONCLUSIONS: We conclude, that some
cytokines, especially IL-6/sIL-6R, could play an important role in development of
renal insufficiency in MM or other monoclonal gammapathies. We suggest that IL-6
levels could be predictive factor for renal insufficiency recovery.
PMID- 9650355
TI - [Soluble cytokinin receptors in renal vasculitis and lupus nephritis].
AB - BACKGROUND: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may
play important role in the pathogenesis of renal vasculitis and lupus nephritis
(LN). Systemic effects of these cytokines may be modulated by their circulating
soluble receptors. Plasma levels of cytokine receptors may thus be also markers
of the activation of these cytokines. METHODS AND RESULTS: Plasma levels of TNF
alpha, its soluble receptor p75 (sTNF-RII), IL-6 and soluble IL-6 receptor (sIL
6R) were measured using ELISA in 17 pts with ANCA-positive renal vasculitis (12
active-ANCA-A, 7 in remission ANCA-R), 9 pts with active lupus nephritis (LN) and
5 healthy subjects. Pts with LN had in comparison with controls increased plasma
levels of TNF alpha, sTNF-RII, IL-6 and sIL-6R. Pts with ANCA-A had also in
comparison with controls increased plasma levels of TNF alpha, sTNF-RII and sIL
6R, but plasma levels of IL-6 were not significantly increased dut to great
standard deviation. Pts with ANCA-R had in comparison with controls increased
plasma levels of sTNF-RII, but plasma levels of TNF alpha were in ANCA-R
significantly lower than in ANCA-A. While the ratio TNF alpha/sTNF-RII was
significantly lower in all groups of pts than in controls, the ratio IL-6R/sIL-6R
was in comparison with controls significantly increased only in LN. CONCLUSIONS:
While increased plasma levels of TNF alpha may be nonspecific marker of the
activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are
increased also in pts with ANCA-positive renal vasculitis in remission. Increased
plasma levels of sTNF-RII may interfere with systemic effects of TNF alpha, but
may also prolong the lifetime of its active form. Plasma levels of sIL-6R are
increased both in ANCA-A and in LN, but their increase is, however, much less
pronounced than that of sTNF-RII and cannot effectively block systemic effects of
IL-6.
PMID- 9650356
TI - [Dangerous religious sects].
PMID- 9650357
TI - [Beta blockers in the treatment of arterial hypertension].
AB - The authors present a detailed review on beta-blockers (BB) in the treatment of
hypertension. In the introduction they deal with the organ distribution and
effects of stimulation of adrenergic receptors, followed by a detailed
classification of beta-blockers by selectivity and the presence of internal
sympathetic activity (ISA or PAA). The mechanisms of the antihypertensive action
of beta-blockers are due mainly to a reduction of the minute volume. However,
other possible effects of BB are also mentioned. The authors discuss in detail
the use of BB in hypertension and associated diseases, side-effects of BB,
contraindications for their administration, possible interaction with other
groups of drugs and the strategy of their use in patients with high blood
pressure.
PMID- 9650358
TI - [Spiral (helical) computer tomography].
AB - The introduction of spiral (helical) computed tomography (CT) has revolutionized
the way established body CT examination are performed and has created new
examinations as CT angiography. The production of overlapping images from single
short X-ray exposure, the minimization of motion artefact and the suppression of
respiratory misregistration have all improved performance of routine CT
examinations. These same technical advantages have also led to the development of
new applications. With advanced 3-D postprocessing applications, simulated
endoscopy is made possible permitting the radiologist the view anatomy from
within any lumen or anatomic space within the body.
PMID- 9650359
TI - [Chronic fatigue syndrome].
AB - A great concern is recently given to the chronic fatigue syndrome in the Czech
Republic. Unfortunately, published data allow us to state neither the etiologic
agent nor the pathophysiology of the disease. Although many authors published
various laboratory abnormalities, these changes are inconstant and do not allow
to state a diagnosis of the chronic fatigue syndrome by a single laboratory test,
and effective therapy is not known either. Psychotherapy, and in some cases
antidepressants, are recommended by some authors to alleviate patient's symptoms.
Neither immunological nor antiviral therapy showed positive results in controlled
trials and are not generally used in most centers.
PMID- 9650361
TI - [What was not included in the recommendations for the diagnosis and therapy of
hyperlipoproteinemia in childhood].
AB - Screening and treatment of hyperlipidaemia should be the concern of
paediatricians. This is suggested by the finding of fatty streaks and other
atheromatic changes in children. The authors prefer selective to nationwide
screening in children who have close relatives with coronary heart disease or
cerebral haemorrhage before the age of 55 years in men and 65 years in women or
elevated total cholesterol levels. In case of repeated total cholesterol levels
of 4.4-5.2 mmol/l the authors recommend annual, in case of levels above 5.2
mmol/l 3-6 month intervals between examinations. The authors found values above
5.2 mmol/l in one quarter of otherwise healthy children. In addition to the
hyperlipidaemic theory there is the infectious theory of development of
atherosclerosis and the theory of programming of coronary heart disease during
pregnancy. By dietary and lifestyle provisions it is possible to reduce
hyperlipidaemia in the great majority of children. In boys above 10 years and
girls above 20 years resins are indicated if the total cholesterol level is above
8 mmol/l.
PMID- 9650360
TI - [The effect of pharmacologic prophylaxis with Panpal on acetylcholinesterase
activity in the diaphragm and various parts of the brain in rats during treated
and untreated Soman poisoning].
AB - BACKGROUND: The pharmacological prophylaxis protecting the organism against
organophosphorus compounds could increase the effect of antidotal treatment of
poisoning with organophosphates. METHODS AND RESULTS: The influence of the
pharmacological prophylaxis with Panpal (pyridostigmine in combination with
benaetyzine and trihexyphenidyle) on acetylcholinesterase activity in diaphragm
and various parts of brain at 1 and 3 h following non-treated and treated (the
oxime HI-6 in combination with atropine) soman poisoning was tested on male rats.
While Panpal did not significantly influence the acetylcholinesterase activity in
brain following non-treated as well as treated soman poisoning. Panpal increased
so many-induced acetylcholinesterase inhibition following non-treated poisoning
and decreased the reactivating effect of the oxime HI-6 following treated soman
poisoning in diaphragm. CONCLUSIONS: Our data confirm the importance of the
combination of reversible acetylcholinesterase inhibitor pyridostigmine with
anticholinergic drugs in the pharmacological prophylaxis of soman poisoning
because of the elimination of consequences of pyridostigmine-induced increasing
in acetylcholinesterase inhibition in the peripheral compartment.
PMID- 9650362
TI - [Hypertensive crisis and its treatment].
AB - Hypertensive crises threaten, due to the rapid rise of blood pressure the
patient's life by cerebral, cardiovascular and renal complications. It may cause
left-sided heart failure, dissection of the aorta, cerebral haemorrhage, renal
failure. Patients with hypertensive crises are admitted to intensive care units
with the possibility of systematic monitoring of the pulse rate, BP, ECG,
diuresis and other vital functions. Treatment is started immediately by
injections (usually i.v.) of antihypertensive drugs while monitoring the BP,
vital functions and the general condition. At first small amounts of
antihypertensives are administered and, depending on the BP, the dosage is
adjusted. The recommended safe drop of BP which should be achieved within one
hour is 100-110 mm Hg of diastolic BP or a 20% drop of the initial pressure.
Concurrently with injections oral administration of antihypertensives is started.
Correct treatment leads in the majority of patients to regression of hypertension
and of acute danger to the patient's life. On the other hand, inadequate
treatment threatens the patients with fatal complications.
PMID- 9650363
TI - [The Christian search for health and treatment of illness].
AB - The link between Euro-American medicine and Christian ways of thinking is
essentially beyond doubt. Deviations from and tension between so-called mundane
philosophy of health and disease and theological views ensure rather from
bilateral non-communication and isolation. Christian thinking owes the world more
profound and more up-to-date study of anthropological and biological problems.
The philosophy of medicine needs also innovations and more convincing spiritual
foundations.
PMID- 9650365
TI - [Practical experience in providing pharmaceutical services in public pharmacies
in Denmark].
AB - The paper evaluates practical activities of the public pharmacy in Denmark, which
materialize the content of the so-called pharmaceutical care in everyday contacts
of the pharmacist and patients. It has been found that the conception of
pharmaceutical care is materialized in somewhat different ways in different
countries and in different types of establishments (clinical pharmacy--public
pharmaceutical service). The Czech pharmaceutical service could link up with the
tradition of the 1970s and 1980s when there were efforts to make pharmacist's
work more effective, aiming at solving the patient's problems concerning
medication. This is a world-wide trend worth joining.
PMID- 9650366
TI - [Relation between chemical structure and antimycobacterial activity against
atypical strains. XIII. Thiosalicylanilides].
AB - On the basis of a preliminary study of antimycobacterial activity of
thiobenzanilides a series of eight thiosalicylanilides have been prepared.
Synthetized compounds have been examined in vitro against Mycobacterium
tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium
fortuitum. All compounds have been found very active. The values of minimal
inhibitory concentrations are summarized in Table 1. 3',4'-Salicylanilide was
selected for the following research. The compound have been found inactive in
vivo (on experimental murine tuberculosis).
PMID- 9650367
TI - [Azabischalcones--a new class of potential antitubercular agents].
AB - A series of substituted azabischalcones Ia-Ip, monochalcone II and
dihydroxyderivative III has been prepared and examined for their in vitro
activity against Mycobacterium tuberculosis, Mycobacterium kansasii,
Mycobacterium avium, Mycobacterium fortuitum as well as INH-resistant strains.
Several compounds under study have the same activity as INH and greater than PAS,
Contebene, Ethionamide. The results are summarized in Table 1. In the case of
compound Ie, its in vivo activity was studied against M. tuberculosis as well
(see Table 2). The toxicity of compounds under study is very low--2000
mg/kg/mouse.
PMID- 9650368
TI - [Antiedematous activity of certain arylcarboxylate copper aquacomplexes].
AB - Using rat paw carrageenan edema, the anti-inflammatory activity of nine selected
arylcarboxylatocopper(II) aquacomplexes of the general composition
Cu(RCOO)2.nH2O, where R represents 2-hydroxy-Y-methylphenyl, Y = 3 (n = 1.5), 4
(4) or 5 (2); 2-hydroxy-3,6-dimethylphenyl (n = 4); 2,5-diacetoxyphenyl (1); 2
methoxy-(1) and 4-methoxyphenyl (3); 2-furyl (3) and 2-thienyl (1), was assayed
and compared to that of the free acids. Copper(II) salicylate tetrahydrate and
salicylic acid were used as standards for comparison. All compounds were applied
i.p. in a single dose of 50 mumol/kg body weight, calculated for the RCOO
fragment. m-Cresotato- (mean edema reduction 70%) and p-cresotatocopper(II) (80%)
aquacomplexes were clearly more effective than copper(II) salicylate tetrahydrate
(55%). The nonsubstituted hydroxyl of the salicylate skeleton of acidoligands is
required for the activity of the complexes and of free acids tested. Isomeric
cresotic acids (82-47-62%) and 2-furoic acid (48%) exhibited a higher effect than
salicylic acid (42%). The relationship between the coordination-chemical
properties and the biological effects of the complexes studied is discussed.
PMID- 9650369
TI - [Topical preparations for burns and their evaluation].
AB - The study focused on some problems connected with the formulation of the topical
preparation of the hydrocream type, intended for the treatment of dermal burns.
Seven cream bases containing Emulgator E 2155, Polysorbate 80 and silicone oils
were evaluated. The employed drugs included carbizocaine, lidocaine,
chlorohexidine, and the immunomodulating substance glucan. A measurement of the
surface tension of chlorohexidine and carbizocaine did not reveal interaction
between these two drugs. Liberation tests confirmed a higher release of lidocaine
in comparison with carbizocaine and chlorohexidine. The silicone oil present did
not influence the release of carbizocaine, but it promoted the release of
lidocaine and chlorohexidine. The determination of rheological parameters
revealed that an addition of drugs influenced the flow properties of creams. The
suitability of cream ointments was evaluated on the basis of their drying.
PMID- 9650371
TI - [Analysis of the activities of the Information Service of the National Institute
for Drug Control].
AB - An analysis was carried out concerning the questions regarding drug information
solved by the information service section of the State Institute for Drug Control
(SUKL) in 1992-1995. A rapid decrease in the number of questions was observed
during the period under study. This trend was mainly caused by a decline in
questions regarding the availability of drugs in the market. Questions were posed
in a similar ratio by physicians and pharmacists predominantly from Prague and
surrounding areas. Questions from other categories of health-care professionals
and the lay public are in minority. Most questions focus on the characteristic of
the drug and its availability. AISLP, Martindale and Rote Liste serve as the
principal information sources.
PMID- 9650370
TI - [HPLC analysis of nonsteroidal antirheumatic agents in biological materials. III.
Pyrazolidinediones].
AB - The present paper surveys published HPLC methods estimating pyrazolidinediones in
biological materials and an HPLC method for estimation of kebuzone in the samples
of whole blood, isolated erythrocytes and plasma. An addition of propyl gallate
prevented undesired oxidation of kebuzone. For liquid-liquid extraction, kebuzone
was analysed on the reverse phases Separon SGX C-18 with the mobile phase
methanol--water (pH 2.7) and detected at 247 nm. The elaborated method was used
in a pharmacokinetic study of kebuzone on rabbits.
PMID- 9650372
TI - [Antiedema activity of selected compounds with a gallate skeleton].
AB - Using rat paw dextran-induced and carrageenan-induced edemas, the anti
inflammatory activity of gallic acid (I), triacetylgallic acid (II) and
monohydrate copper(II) triacetylgallate (III) was assayed. All compounds tested
were applied i.p. in a single dose of 50 mumol/kg body weight, calculated for the
RCOO-fragment. The average antiedematous activities in dextran/carrageenan edemas
were decreasing in the following order: III (55.9/41.8%) > I (38.6/31.1%) > II (
3.4/13.3%). The relationship between the biological effects found and gallic acid
as well as its structural derivatives is discussed.
PMID- 9650373
TI - A comparison of three preinduction cervical priming methods: prostaglandin E2
gel, Dilapan S rods and Estradiol gel.
AB - The aim of the study was to evaluate the efficacy of three cervical priming
methods. From January 1, 1994 to December 31, 1996 247 patients presenting an
indication for induction of labor with an unripe cervix were randomly assigned to
one of the following preinduction protocols: 0.5 mg of Prostaglandin E2 gel
administered intracervically (n = 83), four hygroscopic Dilapan S rods applied
intracervically (n = 82), and 150 mg of Estradiol gel administered intravaginally
(n = 82). The inclusion criteria were the patient's informed consent, singleton
pregnancy of more than 36 weeks, cephalic presentation, Bishop score < 5 points
and reactive non-stress test. If the cervical maturation (Bishop score > or = 5,
and/or Bishop score augmentation by 2 points) did not occur after 14 hours of
priming, the case was considered a failure. In the opposite case the patient was
induced by means of extraamniotic PGE2 administration. The mean gain in the
Bishop score was 3.7 points in the PGE2 group 3.9 points in the Dilapan S group,
and 2.8 points in the Estradiol group. 71 patients (85.5%) were successfully
preinduced in the PGE2 group, 73 (89.0%) in the Dilapan S group, and 63 (76.8%)
in the Estradiol group. Labor was induced by preinduction only in 23 patients
(31.3%) of the PGE2 group in 17 (20.7%) of the Dilapan S group, and in 14 (17.1%)
of the Estradiol group. The mean induction to delivery interval was 7 h 27 min in
PGE2 group, 7 h 49 min in the Dilapan S group and 9 h 15 min in the Estradiol
group. The Caesarean section rate was 24.4% in the PGE2 group, 10.5% in the
Dilapan S group, and 24.4% in the Estradiol group. PGE2 gel and Dilapan S rods
proved higher efficacy than Estradiol gel. The highest frequency of labor induced
by preinduction only was in the PGE2 group. There were shorter induction to
delivery intervals in the PGE2, and Dilapan S groups. The lowest Caesarean
section rate was in the Dilapan S group. Neither serious side effects nor
negative neonatal outcome were noted in either group.
PMID- 9650374
TI - [Personal experience with diagnosis of complete hydatidiform mole based on DNA].
AB - In our study we analyzed 13 cases of histologically defined complete hydatidiform
mole (CHM), by using cytogenetic and molecular genetic methods. There were seven
homozygous and six heterozygous CHM. In one case of heterozygous CHM we found a
biparental contribution to genomic DNA. This is evidence of a more heterogeneous
etiopathogenesis of hydatidiform mole.
PMID- 9650375
TI - [MESA, TESA, TESE + ICSI: results of the first 50 cases].
AB - During the period between February 1996 and August 1997 51 infertile men were
operated. The authors evaluate the results from 47 couples--25 cases of
testicular azoospermia and 22 cases of obstructive azoospermia. The mean age of
the men in the group was 33 years (22-48 years). The follow-up period is 1-18
months. In 17 cases, microsurgical epididymal sperm aspiration (MESA) was made,
in five cases testicular sperm aspiration (TESA) and in 25 men, testicular sperm
extraction (TESE) was performed. In the group with testicular azoospermia it
proved possible to obtain sperm in 12 of 25 cases, i.e. in 48%. In men with
obstructive azoospermia all aspirations were successful, i.e. the yield was 100%.
In this group five children were born, seven pregnancies are under way. Thus
regardless of the etiology of male infertility 12 of 47 cases, i.e. 25.5% were
resolved successfully. When the results of the two groups are differentiated, the
outcome is as follows: in the group with testicular azoospermia one child was
born and two pregnancies are under way, i.e. 12%, in the group with obstructive
azoospermia four children were born and five pregnancies are under way, i.e.
40.9%.
PMID- 9650376
TI - [Clinico-teratologic counseling and the Teratology Information Service].
AB - Medical records of 1179 pregnant women counselled at the Department of Medical
Genetics Klimentska during the period 1990-1995 because of exposure to
medicaments during the preconception period and in the first trimester were
analyzed. Women exposed to antimicrobial agents prevailed (48 per cent). Most
frequent was treatment with Doxycycline, Co-trimoxazole and Metronidazole. 23 per
cent of women were exposed to sex hormones, most frequently to oral
contraceptives and norethisterone. The average gestational age at exposure to
antimicrobial agents was 21.5 days and 30 days at exposure to sex hormones.
Specific features of clinical-teratological counselling and the role of the Czech
Teratologic Information Service are described.
PMID- 9650377
TI - [Occurrence of diaphragmatic hernia in the Czech Republic 1961-1995].
AB - During 1961-1995 the incidence of diaphragmatic hernia on the territory of the
Czech Republic was investigated. From a consecutive series of 5,137,907 births
during the period from 1961-1995 in the Czech Republic 1242 cases of
diaphragmatic hernia were diagnosed, incl. 1233 in born children; 9 were
diagnosed prenatally and the pregnancies were terminated. The mean incidence of
diaphragmatic hernia in born children during the investigation period was 2.36
per 10,000 liveborn infants and when the prenatally diagnosed cases were added,
the mean incidence was 2.39 per 10,000 liveborn infants.
PMID- 9650378
TI - [Occurrence of urinary bladder exstrophy in the Czech Republic 1961-1995].
AB - During the period from 1961-1995 the incidence of extrophy of the urinary bladder
was investigated on the territory of the Czech Republic. From a consecutive
series of 5,137,907 infants born in the Czech Republic in 1961-1995 65 cases of
this defect were diagnosed. The mean incidence of extrophy of the urinary bladder
in born children during the investigation period was 0.14 per 10,000 liveborn.
Nationwide data on the prenatal diagnosis of this defect during the investigation
period are not available so far.
PMID- 9650379
TI - [The importance of hormone receptors in benign breast diseases].
AB - Benign breast lesions are usually divided with regard to the proliferative
activity into three categories. These lesions, depending on their
histopathological characteristics and correlation with epidemiological studies
differ as to the risk of breast cancer. 1. The concentration of hormonal
receptors in the breast tissue in our group correlated with the proliferative
activity of the lesion. 2. A major proliferative lesion and atypical hyperplasia
of the ductal epithelium are a typical precancerous condition. 3. The hormonal
receptor concentration defines, in addition to the histological classification,
the biological activity more accurately. The prevalence of the oestrogen receptor
or its trend to predominate over the progesterone receptor is a serious marker of
imminent cancerogenesis. 4. Based on the prevalence of hormonal receptors it is
possible to select suitable hormonal treatment to suppress the proliferative
potential of the breast lesion. 5. A high level of the oestrogen receptor in non
malignant formations of the breast can be considered a manifestation of increased
sensitivity of this target tissue to circulating oestrogens. It is a question
whether it is the manifestation of mutation of the oestrogen receptor or the
consequence of long-term exposure to uncovered levels of bioavailable oestrogens.
PMID- 9650380
TI - [Pregnancy outcome and perinatal results in a group of women treated with
fertilization in vitro and embryo transfer].
PMID- 9650381
TI - [The Schaut radical vaginal hysterectomy with laparoscopic pelvic
lymphadenectomy].
PMID- 9650382
TI - [Ultrasonography of the uterus in the diagnosis of pathologic states of the
endometrium and uterus].
PMID- 9650383
TI - [Ultrasound findings and revision of the uterine cavity after labor].
PMID- 9650384
TI - [Chromosome markers and balanced translocation in the etiology of infertility].
PMID- 9650385
TI - [Adenomyosis as a possible manifestation of long-term treatment with tamoxifen].
PMID- 9650386
TI - [Pregnancy and labor in Leyden-Moebius myodystrophy].
PMID- 9650387
TI - [Prevention of congenital toxoplasmosis].
PMID- 9650388
TI - [Sirenomelia: the sequence of undevelopment of cloacal membranes].
PMID- 9650389
TI - [Prediction and detection of ovulation in clinical practice].
PMID- 9650390
TI - [Endometriosis].
PMID- 9650391
TI - [Surgical treatment of endometriosis].
PMID- 9650392
TI - [Surgical procedures using hysteroscopy].
PMID- 9650393
TI - [Experience with diagnostic and therapeutic hysteroscopy].
PMID- 9650394
TI - [Importance of laparoscopy in vaginal hysterectomy].
PMID- 9650395
TI - [Laparoscopic hysterectomy of the enlarged uterus: an advanced vaginal technique-
retrospective analytic study].
PMID- 9650396
TI - [Laparoscopic lymphadenectomy and hysterectomy in the treatment of endometrial
carcinoma].
PMID- 9650397
TI - [Registry of complications in gynecologic laparoscopy--initial results-
complications of laparoscopic vaginal hysterectomy].
PMID- 9650398
TI - [Personal experience with laparoscopic hysterectomy].
PMID- 9650399
TI - [Laparoscopic management of gynecologic malignancies--controversies].
PMID- 9650400
TI - [Diagnosis of endometrial pathology in postmenopausal women].
PMID- 9650401
TI - Ethical issues in gynecology.
AB - The authors apply the language and concepts of ethics to the problem of
differences between the gynecologist and the patient about what is in the
patient's interest. We develop a framework for clinical judgment and decision
making about the ethical dimensions of the gynecologist-patient relationship. To
achieve this goal we define the ethical principles of beneficence and respect for
autonomy. We then show how these two principles interact in clinical judgement
and decision making using common examples from gynecologic practice. We examine
factors that influence the relative weight of these principles, including subject
matter, probability of net medical benefit, availability of reasonable
alternatives, and ability of the patient to participate in the informed consent
process.
PMID- 9650402
TI - [The National Register for Assisted Reproduction: results and analysis of
complications].
AB - 1. Analysis of achieved results of assisted reproduction provides evidence of a
steadily increasing success of ART methods in the Czech Republic. 2. Analysis of
results and complications makes it possible a) to prove optimal therapeutic
procedures in different groups of patients b) to recommend preventive measures to
avoid complications c) assess possible side-effects on women and the foetus.
PMID- 9650403
TI - [Reduced serum dehydroepiandrosterone levels in postmenopausal osteoporosis].
AB - The decline of the production of several hormones with age has been recently
linked to several degenerative processes related to aging including osteoporosis.
The aim of our study was to confirm the observations published in 1994 suggesting
that postmenopausal women with DHEAS levels below a certain limit have a much
higher risk of osteoporosis than those with the levels above this limit. The
DHEAS levels were measured by RIA and compared to our own age-adjusted reference
ranges. The values lower than 25th quantile were considered "subnormal". More
than 500 postmenopausal subjects were included in our study. In those with
"subnormal" levels bone mineral density (BMD) was measured on DEXA (Lunar or
Hologic). Decreased BMD ranging from osteopenia to severe osteoporosis was found
in 86% of 74 women with "subnormal" DHEAS, while the expected frequency in our
postmenopausal population may be about 30%. In the following period the serum
DHEAS levels were compared with DEXA findings in another 134 postmenopausal
women. The DHEAS levels in all stages of decreased BMD were significantly lower
than those in the group with normal BMD. The clinical sensitivity and specificity
of DHEAS as a marker of increased risk of osteoporosis has been calculated for a
cut-off limit of 0.5 MoM. In the light of these findings we believe that the
robust and relatively cheap DHEAS determination could help us to identify women
who are at higher risk of osteoporosis. Also, in the future, only the women with
evidently deficient DHEA production might possibly become candidates for eventual
DHEA substitution.
PMID- 9650404
TI - [The biology of menopause].
PMID- 9650405
TI - [The role of the vascular endothelium and reactive forms of oxygen and nitrogen
in the pathogenesis of preeclampsia].
PMID- 9650406
TI - [Pfannenstiel--a software program for video documentation of surgical records in
gynecology].
PMID- 9650407
TI - [Laparoscopy in chronic pelvic pain].
PMID- 9650408
TI - [Importance of vaginal sonography and curettage in the diagnosis of dysfunctional
hemorrhage].
PMID- 9650409
TI - [Primary vaginal carcinoma].
PMID- 9650410
TI - [Use of variable number of tandem repeat polymorphism in assessing correct
sampling in prenatal diagnosis of monogenic disorders].
PMID- 9650411
TI - [Current laws on venereal diseases: notification of sexual diseases, contact with
laboratories, serology of lues, culture and diagnosis of gonorrhea, recourse in
noncompliance, isolation in health care facilities].
PMID- 9650412
TI - [Adenosarcoma of the uterus in a 19-year-old patient].
PMID- 9650413
TI - [Recent and old history of the Czech Gynecologic and Obstetrical Society].
PMID- 9650414
TI - [Professor Karel Klaus--a classical figure in Czech obstetrics].
PMID- 9650415
TI - [Review of the molecular genetics of the Lynch syndrome].
AB - The molecular genetics of the hereditary nonpolyposis colorectal cancer (HNPCC,
Lynch syndrome) is reviewed. Recently, four genes (hMSH2, hMLH1, hPMS1, hPMS2)
whose mutations are related to HNPCC were discovered. The products of these genes
are homologues of the bacterial mismatch repair (MMR) system proteins MutS and
MutL. Dysfunction of MMR system both in bacterial and human cells leads to the
microsatellite instability (MI) in repetitive sequences of DNA. These sequences
are also present in some tumor suppressor genes (e.g. TGF-beta RII or BAX).
Therefore, the MI probably leads to the impairment of the cell cycle regulation
and a carcinoma can develop from the clone of such cells with nonregulated
growth.
PMID- 9650416
TI - [Hormonally active peptides].
AB - The article reviews hormonally active peptides, mechanisms of their biosynthesis
and chemical synthesis. Special attention is given to achievements of the Czech
school of peptidology. Mechanisms of activity of peptidergic hormones is based
mainly on the activation of adenylatcyclase and formation of the "second
messenger", cAMP. Other three possible mechanisms are also reviewed. Main groups
of peptidergic hormones (neurohypophyseal hormones, hypothalamic regulatory
hormones, gastrointestinal hormones, natriuretic peptides, and many others) are
described and their therapeutic and diagnostic significance is summarised. Future
prospects of peptidology in the clinical praxis are briefly reviewed.
PMID- 9650417
TI - [Intracranial hypertension].
AB - Intracranial hypertension is a serious consequence of the impaired intracranial
volume homeostasis. It can be encountered in practically all fields of clinical
praxis. The article reviews bibliographic data of the mechanisms of the
intracranial hypertension development: Intracranial expansion, Brain edema,
Hemodynamic brain edema, Liquor accumulation--hydrocephalus. A pathophysiological
approach to the hypotheses of edema and brain swelling is stressed. Outlines of
the modern diagnostics and therapy of the intracranial hypertension are
presented.
PMID- 9650419
TI - Neuronal connections, cell formation and cell migration in the perinatal human
hippocampal dentate gyrus.
AB - Jean Piaget's "stage theory" suggests that cognitive development proceeds in
discrete steps, among which the first is the sensorimotor period that occupies
the first two years. In recent years it became clear that an intact and mature
hippocampus is necessary for memory formation both in experimental animals and in
human. In the present experiments the perinatal morphological development of the
human hippocampus was studied to describe structural changes that may correlate
with the developmental changes of intellectual growth. Our results suggest that
cell formation in the human hippocampus terminates several weeks before birth,
but immature cells migrate to their final positions through the first six
postnatal months. The newborn hippocampus contains all cell types and cell layers
that are characteristic for the adult hippocampus. However, changes of the light
microscopic features of the postsynaptic target neurons of hippocampal granule
cells indicate that connections between granule cells and their target neurons
are immature at birth and develop through an extended period of time that may
last for three years. Since this neuronal connection is the first link in the
chain of the main hippocampal synaptic circuitry, it may be suggested that human
hippocampus is functionally impaired at birth. This period of light microscopic
morphological maturation correlates well with the time period of Piaget's first
stage of cognitive development. It can also be suggested that the prolonged
postnatal development of some neuronal circuitries in the human hippocampus may
be responsible for the psychological phenomenon of "infantile amnesia", that is
the lack of memory traces from the early postnatal period.
PMID- 9650420
TI - Protective effect of flavonoids and tocopherol in high altitude hypoxia in the
rat: comparison with ascorbic acid.
AB - The mixture of flavonoids (silymarin) from Carduus Marianus (0.9 mg.g-1 body
weight) and/or ascorbic acid (0.4 mg.g-1 body weight) were administered in the
food to 21 day-old (b.w. 35-45 g) rats for one week. Then the animals were
exposed, in a hypobaric chamber, to simulated altitude 8,000-12,000 m for one
hour. Mean lethal altitude was calculated by the Behrens equation: it was 10,150
m in controls, 10,550 m in ascorbic acid treated, 10,500 m in silymarin and
tocopherol treated and 10,450 m in animals, receiving both ascorbic acid and
silymarin. Thus silymarin protected the animals against lethality of high
altitude hypoxia. The effect of ascorbic acid and silymarin were not additive.
PMID- 9650421
TI - On the intrinsic mechanisms of spontaneous motility in chick embryos.
AB - Our experimental study was aimed on the problems of co-operation of NMDA- and NO
ergic mechanisms in the genesis of spontaneous motility in 17-day-old chick
embryos. 1. Blockade of NO-synthase (NOS) by 7-nitro indazole prevented effect of
an activation cocktail (NMDA + L-arginine). 2. Simultaneous blockade of NOS and
of polyamine site in NMDA-receptor by arcaine was revealed by increased NMDA
activation of the spontaneous motility and by blockade of L-arginine and cocktail
effects. 3. The blockade of NMDA-activation, depression of L-arginine activation
and short-lasting potentiation of cocktail effect. 4. Blockade of NMDA mechanism
by Mg2+ abolished activatory effect of both NMDA and L-arginine. The initial
activation remained from the cocktail effect only. Results were considered as an
evidence of a possible co-operation among NMDA- and NO-ergic mechanisms in the
development of the embryonic spontaneous motility.
PMID- 9650422
TI - [Developmental neuronal plasticity and its importance in the recovery and
function of neural tissue].
AB - Plasticity is understand as a natural ability of the nervous tissue to respond to
intrinsic and extrinsic stimuli by means of functional or structural changes. All
its manifestations, including the developmental changes and processes of recovery
are controlled by general genetic programs. One of the major research goals in
the field of neuroplasticity is to design a strategy for the activation of the
functional recovery. Enough evidence has shown that the internal environment of
the nervous tissue is one of the decisive factors which determine the degree of
both the developmental and regenerative plasticity. To improve capacity for the
recovery it is therefore necessary to activate these intrinsic neuroplastic
mechanisms. One alternative is the method of implantation of the embryonal nerve
cells suspension into the site of neuronal lesion. The grafted cells can either
replace the lost cells or they might become a source of stimulating factors which
may activate the process of recovery. In the model of the intrahippocampal
pathways interruption (experimental partial elimination of granule cells in the
dorsal blade of the dentate gyrus), the subsequent implantation of embryonal
neurons of the same origin into the site of lesion can partly restore the
structural pattern of the gyrus dentatus and probably preserve some of the
afferent connections. However, the outgrow of efferent fibers probably remains
limited to the grafted tissue.
PMID- 9650423
TI - [Intermittent hypobaric hypoxia during development--morphologic changes in the
neocortex and hippocampus].
AB - Infant rats, together with their mother, were exposed to the simulated altitude
of 7,000 m for 8 hours per day since birth to the age of 18 days. Animals were
studied the 25th day, 7 days after the last exposure to hypoxia. The experimental
and control animals were killed the 25th day by the transaortic perfusion with 4%
buffered neutral formaldehyde under ether anaesthesia. Brains were processed for
classical neurohistological analysis (Nissl staining). 1. Cortical area in the AP
plane 3 mm posterior to bregma were subjected to quantification and "laminar
analysis" of the neuron count. 2. Hilus of the dentate gyrus between the AP plane
2.5 mm and 4 mm posterior to bregma were subjected to quantification of the
neurons. The findings were as follows: a) The cytoarchitectonics of the brain in
animals exposed to hypoxia was not severely damaged. b) The thickness of
neocortex is in the experimental animals lower than that in the controls. c) The
"laminar analysis" of neocortex showed a relative increase of neuronal density in
layers I., II., V. and VI. of the cortex. d) The quantification of the neuron
count showed a decrease in hilus of the dentate gyrus. These results demonstrate
that the intermittent hypobaric hypoxia has a profound effect on morphological
maturation of central nervous system in infant rats.
PMID- 9650424
TI - [Postictal depression in 12-day-old animals].
AB - Postictal depression systematically follows epileptic after-discharges (AD)
evoked from many different regions of the brain of adult animals. In presented
experiments we tested by evoking ADs from sensorimotor cortex whether the
susceptibility to undergo postictal depression is age-dependent and whether it
correlates with the individual duration of ADs. Groups of 12-, 18- and 25-day-old
male rats were used (freely moving animals--semichronic preparations; six trains
of rhythmic electrical stimulations in one min. intervals after the end of
previous seizure; EEG recordings; durations of ADs were measured). In the whole
group of the 25-day-old animals the mean duration of ADs after individual
stimulations illustrated the inhibitory influence of the first seizure on the
duration of all subsequent ADs. In 18-day-old animals the depression was less
pronounced and in 12-day-old it seemed to be not present. Analysis of results in
individual animals in the group of youngest animals showed, that duration of
pairs of subsequent seizures was related to the duration of the first of them.
Also in this age group long seizures caused postictal depression. Duration of
seizures seems to vary individually and it strongly influences the mean results
of the whole group. The differences between the groups could be explained on the
basis of the different pattern of ADs in young and older animals. In young
animals the total "output" of seizure is low and it could also cause not so
intensive and long posttetanic depression based on changes of intracellular Ca2+,
because this form of synaptic plasticity seems to involve the activation of
Ca(2+)-dependent protein kinases. Synaptic energy consumption also may play some
role in postictal depression occurrence.
PMID- 9650425
TI - [Morphologic and functional characteristics of an animal model of cerebellar
degeneration (lurcher mutant mice)].
AB - Lurcher mutant mice are characterized by genetically determined degeneration of
cerebellar Purkinje cells, granule cells and inferior olivary neurons (ION). In
the morphological part of this study Lurcher mutant and wild type mice were given
intraperitoneal injections of 3-acetylpyridine (3AP) to look at the effect of
this neurotoxin and niacinamide antagonist on the ION. Intraperitoneal
administration of 3AP is characterized by the different sensitivity of ION in
Lurcher mutant mice and wild type mice in both infant and young adult animals.
Lurcher mutants suffered a destruction of these neurons while wild type mice were
unaffected. Since the cerebellum plays an essential role in the sphere of motor
learning and behavior, in the functional part of this study we investigated some
characteristics of early learning in Lurcher mutant and wild type mice. The first
experimental results show some differences in the inhibitory reaction of the
passive avoidance between Lurcher mutant and wild type mice in early ontogeny,
during the first month of their life. Both morphological and functional findings
show not only different effects of 3AP on genetically mutated and wild type mice
in the same inbred strain but also some functional changes in the sphere of early
learning and memory as well.
PMID- 9650426
TI - [Pathophysiology: the past, present and future].
PMID- 9650427
TI - Prostate cancer: local staging with endorectal magnetic resonance imaging.
AB - BACKGROUND: Prostate cancer has received increasing attention during the past
decades. Staging of tumors before treatment is imperative for planning
appropriate therapy. The purpose of this study is to assess the role of
endorectal magnetic resonance imaging (MRI) in local staging of prostate cancer.
METHODS: Endorectal MRI was performed in 31 patients with histologically-proven
prostate cancer. MRI was done three to 100 days (mean, 32.1 days) after either
transrectal ultrasonography (TRUS) with biopsy or transurethral resection of the
prostate (TURP). Radical prostatectomies were performed within two weeks after
MRI. The diagnostic accuracy of endorectal MRI for local tumor staging,
specifically for extracapsular extension (ECE) and seminal vesicle invasion
(SVI), was evaluated by correlating MRI results with histopathologic findings of
whole-mount specimens. RESULTS: The accuracy of endorectal MRI for the detection
of tumor presence and estimation of tumor volume was 48%. Sensitivity,
specificity and positive predictive value for evaluation of ECE were 88%, 69% and
80%, respectively, and for SVI, were 66%, 84% and 50%, respectively. The overall
accuracy of MRI in local tumor staging (using the TMN system) was 61%. Accuracy
in differentiating localized from invasive cancer was 84%. CONCLUSION: Endorectal
MRI is not accurate enough to detect tumor presence or estimate tumor volume.
Diagnostic accuracy for local tumor staging is unsatisfactory. However,
endorectal MRI is highly accurate in differentiating localized (stage B) from
invasive (stage C) cancer.
PMID- 9650428
TI - Prediction of right ventricular infarction from standard surface ECG in patients
with inferior myocardial infarction.
AB - BACKGROUND: Patients with inferior myocardial infarction (MI) have a 45% chance
of having concurrent right ventricular infarction (RVI); of these, 5-10% suffer
hemodynamic collapse. Immediate correct diagnosis and appropriate management of
such patients is vital. ST-segment elevation in the right precordial V4 lead
(V4R) has a high diagnostic value in identifying RVI, but this determination
requires additional time and cost. An attempt was made to use a collection of
patients' standard surface electrocardiograms (ECG) to find any available data to
detect RVI and to lead to a new way to diagnose RVI. METHODS: Fifty patients
(males/females, 44/6; mean age, 64.3 +/- 6.9 years) with acute inferior
myocardial infarction were enrolled in a first group to develop new diagnostic
criteria for RVI. As a first step, the ST-segment change in every standard
surface ECG lead was analyzed and compared with corresponding changes in V4R. RVI
was diagnosed by typical clinical symptoms (chest pain for more than 30 minutes,
ST elevation > 0.1 mV and enzyme changes) accompanying ST elevation of more than
0.1 mV in V4R (by Lopez-Sendon criteria) and echocardiographic findings. RVI was
diagnosed in 24 (48%) patients using ECG. The new criteria were then tested in a
secondary group of 48 patients (males/females, 43/5; mean age, 65.5 +/- 7.9
years) with inferior MI. RESULTS: Analysis of these patients found that ST
depression in lead I and aVL was a specific characteristic of RVI (I + aVL > 0.2
mV). This criterion was applied to another group of patients with acute inferior
MI to check the predictive value (sensitivity, 94.7%; specificity, 89.7%;
positive predictive value, 85.7%; negative predictive value, 96.3%). CONCLUSIONS:
In patients with evolving inferior MI, standard surface ECG analyzed for this
criterion could aid clinical recognition of concomitant RVI.
PMID- 9650429
TI - Endovascular embolization of arteriovenous fistulas of the external carotid
artery.
AB - BACKGROUND: External carotid arteriovenous fistulas (AVFs) are rare and most
hospitals have limited experience with their management. This study was designed
to evaluate the effectiveness and safety of endovascular embolization of AVFs of
the external carotid artery under angiographic control. METHODS: A series of 13
patients with AVFs involving the branches of the external carotid artery, all
treated with endovascular embolization, were reviewed. There were 10 males and
three females ranging in age from nine to 46 years, with a mean of 27 years. The
most frequent presenting symptoms were pulsatile tinnitus, followed by bruit
and/or thrill, ocular problems, headache and a pulsatile mass in the neck. The
middle meningeal artery was most often involved, followed by the internal
maxillary artery and the occipital artery. The AVFs were caused by trauma in 10
patients and occurred spontaneously in three. N-butyl-2-cyanoacrylate was used to
embolize the fistula in 11 patients and a detachable balloon was used in two.
RESULTS: All the patients were cured and no significant complications were
observed. No recurrence was noted after a clinical follow-up of three months to
seven years (mean, 37 months). CONCLUSIONS: Endovascular embolization proved to
be a safe and effective procedure. It should be the treatment of choice for
repair of external carotid AVFs.
PMID- 9650430
TI - Analysis of costs borne by families of patients hospitalized for stroke.
AB - BACKGROUND: Studies focusing on the economic impact of cancer on families have
emphasized that costs of chronic disease are substantial for patients and their
families. However, little effort has been devoted to measuring the costs of care
for families of patients hospitalized with stroke. METHODS: A total of 215 stroke
patients and their families from four teaching hospitals in the Taipei
metropolitan area were monitored from the date of the patient's admission to
hospital until the date of discharge. The value of labor contributed by families
was estimated by assigning the current monetary market rate of providing health
aide to the time families spent caring for patients in hospital. Lost earnings of
patients and families, expenditure for medical care, and expenses for food,
clothes, adult diapers, transportation and other miscellaneous items were
determined and summed to arrive at the total family cost of providing care.
RESULTS: The average cost of care for one family per inpatient day was
NT$4,358.20. A total of 98.6% of the families incurred labor costs, which
accounted for about half of family costs for providing care. Hospital bills
accounted for almost 19% of total family costs. The income loss for families and
patients accounted for about 25% of total family costs. Expenses for food,
clothes, transportation, diapers and other illness-related miscellaneous items
accounted for about 12% of total family costs. Multiple regression analyses
demonstrated that the number of family members involved in giving care and the
length of stay are important predictors for the total cost of care. Average total
family costs per day increased by 24.3% when an additional family member was
involved in providing care. Total family costs increased 2.5% for each hospital
day. CONCLUSIONS: If direct and indirect nonmedical costs are not included in the
total cost calculation for providing hospital care to stroke patients, the
economic impact of care on families is likely to be underestimated.
PMID- 9650431
TI - Endoscopic vein harvest for coronary artery bypass surgery.
AB - BACKGROUND: Despite increased awareness of risk factors, wound complications
continue to be a problem following coronary artery bypass graft (CABG) surgery. A
minimally invasive alternative was therefore developed to reduce the risk of
complications while providing the same benefits as the standard open vein harvest
procedure. METHODS: Video-assisted endoscopic technique for vein harvest was
introduced in our medical center in October 1996. The procedure was evaluated and
compared with the standard open vein harvest procedure. With the endoscopic
technique, small incisions were made, each about 2-3 cm at the selected access
sites (groin and above and below the knee). An endopath subcutaneous dissector
was subsequently inserted along the anterior surface of the saphenous vein with
the assistance of an endoscope and video monitor. The venous side branches were
detected and positioned using a vessel dissector. A ligaclip was applied and the
branches were divided using endopath-scissors. In some cases, the venous branches
were divided directly using the endopath-scissors. Therefore, the distal and
proximal ends of the saphenous vein were isolated, ligated and divided. The
harvested veins were used for CABG. Each patient was evaluated for length of
surgery, hospital stay and morbidity. RESULTS: From October 1996 through May
1997, we performed 50 procedures using video-assisted endoscopic vein harvest.
The results were compared with those from 106 patients who underwent standard
open vein harvest during the same period. The rate of complications was 2% in the
endoscopic group compared with 13.2% in the open group (p < 0.05). The average
hospital stay was 7.2 days in the endoscopic group and 11.5 days in the open
group (p < 0.05). Twelve weeks after the operation, all of the incisions healed
with good cosmetic results in the endoscopic group. However, long visible scars
were found in the patients in the open group. CONCLUSIONS: Endoscopic saphenous
vein harvest provides a minimally invasive alternative to open vein harvest. It
provides good cosmetic results without a hypertrophic scar and enables the
patient to regain early ambulation.
PMID- 9650432
TI - Malignancy following renal transplantation.
AB - BACKGROUND: A markedly increased incidence of malignancy in transplant recipients
is well recognized. However, the incidence and pattern of post-transplantation
malignancies shows some discrepancy among different reports. The renal transplant
recipients monitored at Taichung Veterans' General Hospital comprise the largest
group in Taiwan. An analysis of the characteristics of post-transplant
malignancies emphasizes the differences from malignancies that occur in the
Taiwanese general population and those reported in Western countries. METHODS:
The incidence and characteristics of de novo malignancy in 390 renal transplant
recipients who underwent renal transplantation between May 1983 and June 1996
were analyzed. A total of 232 men and 158 women (mean age at transplantation:
38.5 +/- 10.7 years) were included. The relative risk for developing malignancies
was calculated based on the sex- and age-matched cancer incidence of reference
for the Taiwanese population; data from the Cancer Registry Annual Report in
Taiwan (1989) was obtained for comparison. RESULTS: A total of 25 cancers were
diagnosed in 24 renal transplant recipients, for an incidence of 6.2%. The
relative risk of renal malignancy was 13.8-fold higher among transplant
recipients than in the general population. The impact of gender and age on the
development of post-transplantation malignancy was not significant. The most
common types of cancer were transitional cell carcinoma (TCC) of the urinary
tract (8/25), and hepatoma (8/25), followed by two cases of Kaposi's sarcoma.
Aside from immunosuppressive agents, the high incidence of hepatoma and TCC may
be attributed to the high incidence of hepatitis infection and the possible
carcinogenic effect of abnormal milieu induced by uremia per se. Survival was
largely dependent on the extent of disease at presentation, and post
transplantation cancer did not show more aggressive behavior if detected early.
CONCLUSIONS: The high cumulative incidence of malignancies makes it imperative to
define an effective safe immunosuppressive regimen to achieve a lower risk of
malignancies. In the future, the prime approach to treatment of post
transplantation malignancies should begin with early detection and ensuing
aggressive treatment to improve the outcome.
PMID- 9650433
TI - Rupture of rudimentary horn pregnancy: a case report.
AB - A rare case of rupture of a noncommunicating rudimentary horn pregnancy is
presented. The pregnancy continued to 16-weeks' gestation, when the rudimentary
horn ruptured. The patient had signs and symptoms of massive hemoperitoneum. An
emergency exploratory laparotomy revealed a ruptured rudimentary horn and an
intact amnionic sac. Prompt excision of the rudimentary horn was performed. The
relative literature and factors associated with a rudimentary horn pregnancy are
reviewed and discussed.
PMID- 9650434
TI - Primary retroperitoneal liposarcoma mimicking ovarian cancer: a case report.
AB - Primary retroperitoneal liposarcoma is a rare malignancy comprising about only
0.1% of all cancers. It produces nonspecific symptoms and is often extensive when
diagnosed. In this report, we present a case of a 68-year-old female patient who
had a 29-kg retroperitoneal liposarcoma. Her early symptoms--including vague
digestive disturbances, increasing abdominal girth and an abdominal mass, and
clinical examinations such as sonography and computed tomography scan led to a
preoperative diagnosis of ovarian cancer, until surgical and pathologic
confirmation. Gross, radical resection of the tumor was successfully performed,
and provided the most effective primary therapeutic approach. Histopathology
revealed a mixed-type liposarcoma, with metastasis to the appendix. A poor
prognosis was expected. Postoperative periodic follow-up was started to monitor
for early detection of recurrence.
PMID- 9650435
TI - Focal segmental glomerulosclerosis after poststreptococcal glomerulonephritis in
the elderly: a case report.
AB - Acute poststreptococcal glomerulonephritis (PSGN) is quite rare in the elderly
population. It is very difficult to recognize because the initial symptoms are
similar to those of more common diseases of this age group. Compared with younger
patients, elderly patients with PSGN tend to have a high incidence of renal
function impairment and anuria or prolonged oliguria. Recovery from acute PSGN in
the elderly is less predictable than in children and younger adults, especially
when associated with severe impairment of renal function. We present the case of
an elderly patient with PSGN, who had a skin infection of the face and anuria on
admission. Percutaneous left renal biopsy was performed in the initial
hospitalization period and in the recovery phase of the disease. Renal function
recovered within two months. However, increased urinary white blood cell
sediments with normal serum creatinine concentrations persisted in the successive
three years of follow-up. Renal biopsy was repeated and showed evidence of focal
segmental glomerulosclerosis.
PMID- 9650436
TI - Diagnosis of cerebral toxoplasmosis by a nested polymerase chain reaction: a case
report.
AB - A 24-year-old man infected with human immunodeficiency virus type I rapidly
progressed to acquired immune deficiency syndrome. His clinical picture was
compatible with a presumptive diagnosis of cerebral toxoplasmosis. Application of
a nested polymerase chain reaction (PCR) succeeded in detecting Toxoplasma gondii
DNA in both the venous blood and cerebrospinal fluid specimens. This result
indicates that PCR is a convenient tool for making a rapid and accurate diagnosis
of cerebral toxoplasmosis, especially in developing countries.
PMID- 9650437
TI - Hypnotic susceptibility order effects in waking analgesia.
AB - This study reexamined Spanos, Hodgins, Stam, and Gwynn's (1984) contention that
susceptibility testing order effects generated a relationship between waking
analgesia pain reduction and level of hypnotic responsiveness. Undergraduate
volunteers with no previous hypnosis experience were randomly assigned to two
groups. Group 1 (n = 69) first received a cold pressor pain protocol, and then
was administered the Standford Hypnotic Susceptibility Scale, Form C (SHSS:C).
Group 2 (n = 69) was administered the SHSS:C prior to the cold pressor pain
protocol. Our findings do not support Spanos, Hodgins et al.'s contention that
susceptibility testing order effects generate the often reported relationship
between waking analgesia and level of hypnotic responsiveness. We found
significant partial correlation coefficients between the SHSS:C and nonhypnotic
pain reduction regardless of order of susceptibility testing. Implications
regarding the adequacy of design-generated expectancies to explain hypnotic
analgesia phenomena were examined.
PMID- 9650438
TI - Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C: manual and
response booklet.
AB - The manual and response booklet for the Waterloo-Stanford Group Scale of Hypnotic
Susceptibility, Form C (WSGC) is presented. The WSGC is a group adaptation of the
individually administered Stanford Hypnotic Susceptibility Scale, Form C
(SHSS:C).
PMID- 9650439
TI - Experiential scoring for the Waterloo-Stanford Group C scale.
AB - A scale is presented that assesses subjective experiences associated with the
test suggestions contained in the Waterloo-Stanford Group C scale (WSGC), a group
adaptation of the Stanford Hypnotic Susceptibility Scale: Form (SHSS:C). This
scale, along with the standard behavioral scoring system of the WSGC, was given
to 926 students at the University of Connecticut. Normative data from this sample
indicate that the experiential scoring scale is both reliable and valid as a
measure of suggestibility. It is suggested that it may be useful to supplement
behavioral scoring with experiential scoring when the WSGC is used.
PMID- 9650440
TI - Effects on suggestibility of a new method of active-alert hypnosis: alert hand.
AB - Research has shown that the active-alert method described by Banyai and Hilgard
(1976) produces a similar increase on suggestibility as relaxation-based
techniques, but it has some limitations, including the need for a stationary
bicycle and a certain level of physical fitness. The authors compared that method
with the new "alert hand" method, which emphasizes activity and alertness, but is
simpler and less strenuous. In a repeated measures, counterbalanced design (N =
80), the authors found that (a) the alert hand method produced significantly
higher objective and subjective suggestibility scores than the active-alert
technique, and (b) a high percentage (23%) of volunteers discontinued
participation during the active-alert method but not during the alert hand
method. The alert hand method extends the benefits of active hypnosis to
individuals who may have difficulties with the physical demands required by the
active-alert method, and it seems to enhance suggestibility even more.
PMID- 9650441
TI - Intentionality during hypnosis: an ironic process analysis.
AB - Two studies were completed to test whether responding to hypnotic suggestions
requires intentional effort. Hypnotic suggestions for amnesia were used as an
analog of thought suppression, and Wegner's model of ironic processing was
applied to hypnotic responding. In the first study, participants were required to
maintain suggested amnesia while performing a cancellation task with and without
a cognitive load. The second study required suppression of thoughts of a favorite
car, once with "blank-mind" instructions and then with a suggestion for amnesia.
The results of these studies indicate that dissociated control theory provides
the best explanation for hypnotic responding in one subset of highly hypnotizable
participants, whereas more intentional responding provides the best explanation
for others.
PMID- 9650442
TI - Multicenter cooperative study group in hematology in Japan: the 10-year history
and role of the Japan Adult Leukemia Study Group in Japan.
AB - Leukemia is an uncommon disease. In order to conduct a scientific clinical study,
a large number of patients is required for reliable statistical analysis, and
therefore, multicenter cooperative study is indispensable in leukemia. Not only
in the field of hematology/oncology but also in other fields of clinical
medicine, well-functioning clinical study groups are still rare in Japan. In this
review, the reason why the organization of multicenter cooperative study groups
is difficult in Japan is analyzed. Then the 10-year experience of a self
supporting and quite successful cooperative study group, the Japan Adult Leukemia
Study Group, is reviewed. Finally, the next steps for the Group and the way it
might be successfully led are discussed.
PMID- 9650443
TI - Usage of activating mutations in the analysis of cytokine signal transduction
pathways.
AB - Cytokine signal transduction pathways are highly redundant and complex. The
analysis of the structure and function of signal transduction molecules was
conventionally done by using mutated or truncated receptors, dominant negative
molecules, and knockout mice. These methods are designed to look at the result of
a subtraction of a part of the whole signal transduction pathway. In contrast,
analysis using activating mutations of a signal transduction molecule is designed
to look at the downstream result of one pathway which originated from the
pertinent molecule. This method is less influenced by other signal transduction
molecules which may have an overlapping effect on the downstream molecules. By
combining both the subtraction and activating methods, we can gain more insight
into the complex interactions between signal transduction molecules. An
activating mutation of a signal transduction molecule is usually found as an
oncogene. However, known oncogenes are not always the molecules of interest. In
this review, several methods to create activating mutations of a target molecule
are discussed.
PMID- 9650444
TI - Molecular interaction between factor VII and tissue factor.
AB - Complex formation between serine protease factor VIIa (VIIa) and tissue factor
(TF) dramatically enhances the catalytic activity of VIIa, leading to the
initiation of extrinsic blood coagulation. The recently determined crystal
structure of the complex formed between VIIa and the extracellular domain of TF
has revealed in detail the interacting surfaces of the two molecules. Mutational
and biochemical studies have further identified regions of VIIa and/or those of
TF essential for the high affinity interaction. These studies indicate that the
regions extending from the gamma-carboxyglutamic acid domain through the first
epidermal growth factor-like domain and protease domain of VIIa are involved
separately in the interaction with the distinct sites of TF. The interaction of
TF with the protease domain of VIIa apparently induces a conformational
transition of the VIIa active site. Studies of the chemical modification of VIIa
provided a model for the mechanism of TF-mediated acceleration of VIIa activity.
In this model, the protease domain of VIIa exists in equilibrium between minor
active and dominant zymogen-like inactive conformational states, and preferential
binding of TF to the active state leads to a shift in equilibrium into the active
state, thereby accelerating VIIa activity. Overall docking of TF with VIIa in the
presence of phospholipids further supports a recognition of macromolecular
substrates, such as factors IX and X. Therefore, single VIIa-TF interaction
contains several distinct mechanisms for enhancing the coagulant activity of
VIIa, which may be important for the initiation of coagulation specifically
mediated by TF. Studies of the interaction between VIIa and TF provide not only a
detailed understanding of the regulated initiation of blood coagulation but also
the potential to design novel anticoagulants for the treatment of thrombotic
diseases.
PMID- 9650445
TI - Assessment of mitomycin C sensitivity in Fanconi anemia complementation group C
gene (Fac) knock-out mouse cells.
AB - Fanconi anemia (FA) is a genetic disorder defined by cellular hypersensitivity to
DNA cross-linking agents, such as mitomycin C (MMC). MMC causes increased FA cell
death, chromosome breakage, and accumulation in the G2 phase of the cell cycle.
Recently, Fanconi anemia complementation group C (fac) gene knock-out mice have
been developed, and SV40-transformed fibroblasts were established from fac
homozygous knock-out (-/-), heterozygous (+/-), and wild-type mice (+/+). MMC
sensitivity of these cell lines was assessed by three methods: colony-formation
assay in the presence of MMC, chromosome breakage, and cell cycle analysis to
detect G2 phase arrest. The fac knock-out fibroblasts (-/-) showed a
significantly higher sensitivity to MMC than did fibroblasts from wild-type (+/+)
or heterozygous (+/-) mice (three experiments). In addition, we analyzed
hematopoietic progenitor colony assays of bone marrow cells from fac knock-out (
/-) and heterozygous (+/-) mice. CFU-E, BFU-E, and CFU-GM colony formation from
fac nullizygous mouse progenitors was markedly diminished by MMC when compared to
growth of progenitors from heterozygous mice. These results show that fac knock
out mouse cells mimic the behavior of human FA-C patient cells in terms of MMC
hypersensitivity. The fac knock-out mouse may be used to model some aspects of
human FA and should be useful for understanding the function of the FAC protein.
PMID- 9650446
TI - PLA2-independent induction of CSF-1 gene expression in growth-arrested
fibroblasts.
AB - At the site of a wound or an infection, localized production of colony
stimulating factor-1 (CSF-1) by resident macrophages is chemotactic for
circulating monocytes. Several intracellular signaling pathways, including those
initiated in response to activation of phospholipase A2 (PLA2) have been proposed
to play a role in the regulation of CSF-1 gene expression. The goal of these
studies was to determine whether PLA2 is required for the initial increase in CSF
1 gene expression in serum- or IL-1 alpha-stimulated growth-arrested fibroblasts.
IL-1 alpha- or serum-stimulation of growth-arrested fibroblasts had no effect on
PLA2 enzyme activity and inhibitors of cytosolic or Ca(2+)-independent PLA2
activity had no effect on IL-1 alpha- or serum-mediated increases in CSF-1 mRNA
levels. High concentrations of the PLA2 inhibitors, 4-bromophenacyl lactone and
quinacrine, resulted in a generalized decrease in cellular mRNA levels. Our
results, obtained in fibroblasts, suggest treatment with 4-bromophenacyl lactone
or quinacrine, instead of inhibiting PLA2 activity specifically, results in a
generalized depression of cellular mRNA levels. These data demonstrate that the
initial increase in CSF-1 gene expression in growth-arrested fibroblasts treated
with serum or IL-1 alpha occurs through a PLA2-independent mechanism.
PMID- 9650447
TI - Dual action of CD30 antigen: anti-CD30 antibody induced apoptosis and interleukin
8 secretion in Ki-1 lymphoma cells.
AB - CD30 is a member of the tumor necrosis factor superfamily. In this study, we
examined the effect of four anti-CD30 (aCD30) antibodies (Abs) on CD30-positive
anaplastic large cell lymphoma-derived cell line, Ki-JK. The aCD30 Abs suppressed
[3H]thymidine (TdR) incorporation. With a TdT mediated dUTP-biotin nick end
labeling method, apoptosis was detected in Ki-JK cells at day 5 after the
addition of aCD30 Ab to the culture. Genistein, an inhibitor of protein tyrosine
kinase, had no effect on aCD30 Ab-induced apoptosis. The aCD30 Ab simultaneously
induced interleukin-8 (IL-8) secretion in the Ki-JK cells. In culture of the Ki
JK cells with aCD30 Ab for 5 days, the IL-8 concentration of the cell free
supernatant increased to 240 +/- 16 pg/ml, though the concentration was < 12.5
pg/ml without aCD30 Ab. In combination with aCD30 Ab, genistein decreased the
concentration of IL-8 in day 5 supernatants. Although, doxorubicin and herbimycin
A suppressed [3H]TdR incorporation and induced apoptosis in the Ki-JK cells, they
did not induce IL-8 secretion. Only aCD30 Ab-induced apoptosis was accompanied by
IL-8 secretion. IL-8 mRNA was not detected in the Ki-JK cells by reverse
transcription-polymerase chain reaction assay. IL-8 mRNA was detected 5 days
after adding aCD30 Ab to the culture.
PMID- 9650448
TI - Improved methods of HIV vector mediated gene transfer.
AB - HIV vectors are capable of targeted gene transfer into CD4+ cells. However,
extensive testing of HIV vectors in gene therapy applications is hampered by the
low titer of current HIV vector could be concentrated by approximately 20 times
by sulfonated cellulose column chromatography. No replication competent
cytopathic HIV was detected in the concentrated vector preparation. When the
vector preparation and the target cells were centrifuged at transduction, about a
five-fold increase in the apparent titer was achieved. Accordingly, by combining
these two techniques the overall titer was increased by approximately two orders
of magnitude. Using this high efficiency strategy, we transduced human primary
lymphocytes that are refractory to transduction with currently available viral
vectors. Amplification and sequencing of the integration sites showed that HIV
vectors could stably integrate into the chromosomes of CD4 enriched human
peripheral blood mononuclear cells. These findings indicate that HIV vectors are
useful for the development of gene therapy targeting lymphocytes.
PMID- 9650449
TI - Osteoblastic cells regulate mi gene expression in cultured bone marrow cells.
AB - The microphthalmia (mi) gene encodes a bHLH-Zip protein and certain mutations in
this gene are known to result in osteopetrosis. We examined mi gene expression in
murine bone marrow (BM) cells and calvaria-derived osteoblastic (OB) cells. The
mi message level in BM cells was three- to four-fold higher than that in OB
cells. The mi message level in BM cells alone was not enhanced by 1,25(OH)2
vitamin D3 (vitamin D) which induces TRAP-positive multinucleated cells, but was
enhanced two-fold by the addition of conditioned medium obtained from cultures of
OB cells. The mi message levels in BM cells were also enhanced by macrophage
colony-stimulating factor (M-CSF). The mi message levels in cocultures of BM
cells and osteoblastic MC3T3-E1 cells, which do not support osteoclastogenesis,
were similar to those in the cocultures of BM cells and OB cells. Cocultures of
BM cells with MC3T3-E1 cells did not yield TRAP-positive multinucleated cells,
but they did maintain osteoclast progenitor cells. These findings suggest that mi
is expressed in BM cells that may be under the control of OB cells.
PMID- 9650450
TI - Establishment of novel cell lines derived from two patients with chronic
myelogenous leukemia in blast crisis; IMS-BC1 and IMS-BC2 which exhibit markedly
different sensitivity to apoptosis.
AB - We established two novel cell lines, designated as IMS-BC1 and IMS-BC2, from two
patients with chronic myelogenous leukemia in blast crisis. The two cell lines
were positive for CD13 and CD33 and negative for CD34 and HLA-DR by surface
marker analysis. IMS-BC1 had four Philadelphia (Ph1) chromosomes and a breakpoint
within the 3'-portion of M-bcr, and IMS-BC2 had five Ph1 chromosomes and two
breakpoints within the 3'- and 5'-portions of M-bcr. Both cell lines' growth
activities were moderately suppressed by IFN-alpha. The proliferation of IMS-BC2
was inhibited by IFN-gamma and apoptosis was induced within 72 h, while IMS-BC1
was resistant to IFN-gamma. Fibronectin inhibited the proliferation of the two
cell lines at higher than 10 micrograms/ml, but only IMS-BC2 showed apoptosis.
Transforming growth factor-beta inhibited the proliferation of IMS-BC2 resulting
in apoptosis, while it inhibited that of IMS-BC1 moderately but failed to induce
apoptosis. All-trans retinoic acid (ATRA) inhibited the proliferation of IMS-BC2
at very low concentration (10(-17) mol/l) and induced apoptosis at doses higher
than 10(-9) mol/l within 72 h without terminal differentiation, while IMS-BC1 was
completely resistant to ATRA. The two cell lines showed different responses to
growth inhibitory cytokines and factors. These cell lines should prove useful in
the analysis of mechanisms of apoptosis induced by growth inhibitory cytokines
and factors.
PMID- 9650451
TI - Establishment and characterization of bone marrow stroma-dependent leukemia cell
line, HB-1.
AB - Radiation-induced M361 leukemia bearing mice (M361 mice) show characteristics of
acute myelogenous leukemia (AML) with granulocytosis. Granulocyte-macrophage
colony forming unit (CFU-GM) increased in the bone marrow and spleen and high
activity of colony stimulating factor (CSF) was found in the sera of M361 mice. A
cell line (HB-1) was established from the spleen cells of M361 mice. Injection of
HB-1 cells induced a similar leukemic response as M361 in syngeneic mice. HB-1
cells did not survive in the suspension culture, but proliferated when cultured
on hemopoietic supportive stromal cells (MS-10). HB-1 cells appear to be strictly
dependent on the hemopoietic supportive bone marrow stroma, which would provide a
useful model for the study of cell-cell interactions between hemopoietic cells
and marrow stromal cells.
PMID- 9650452
TI - Prolonged secretion of IL-15 in patients with severe forms of acute graft-versus
host disease after allogeneic bone marrow transplantation in children.
AB - Graft-versus-host disease (GVHD) is one of the most common and fatal
complications that follows allogeneic bone marrow transplantation (BMT). Donor
origin T cells are responsible for the initiation of GVHD. In this report, we
demonstrate that conditioning regimens for BMT resulted in elevated serum levels
of interleukin-15 (IL-15), which reached maximum levels within 15 days and
returned to basal levels within 25 days after allogeneic BMT, in all patients
examined. Thereafter, circulating IL-15 was detected only in patients with grade
III or IV acute GVHD with gut involvement. In contrast, IL-2 was not detected at
any time in these patients. Since IL-15 is able to activate antigen-stimulated T
cells and natural killer (NK) cells, IL-15 may play an important role in the
development of severe forms of acute GVHD.
PMID- 9650453
TI - Elevated expression of differentiation inhibitory factor nm23 mRNA in monoblastic
crisis of a patient with chronic myelogenous leukemia.
AB - Differentiation inhibitory factor nm23 gene has been found to be expressed in
high quantities in acute myelogenous leukemia (AML), especially in acute
monocytic leukemia (AML-M5) and is suggested as a new prognostic factor in AML
M5. We report an example of elevated expression of nm23 mRNA in a patient with
chronic myelogenous leukemia (CML) who developed monoblastic crisis. Relative
levels of nm23-H1 and -H2 mRNA extracted from the patient's peripheral blood
mononuclear cells and bone marrow mononuclear cells were measured by quantitative
reverse transcriptase polymerase chain reaction. The level of nm23-H1 mRNA in CML
cells at the chronic phase was as high as that in bone marrow cells from healthy
volunteers. The mRNA level of nm23-H2 was slightly below the normal level. At
blastic crisis, however, expression of both nm23-H1 and -H2 mRNA was elevated to
about three to nine times of that at the chronic phase. Proliferated blastic
cells were positive for non-specific esterase, and the serum lysozyme level was
elevated and diagnosed as monoblastic crisis. The patient received combined
chemotherapy but response was partial. These findings are compatible with our
previous report that nm23 gene is overexpressed in monocytic leukemia.
PMID- 9650454
TI - Development of Epstein-Barr virus-associated B cell lymphoma after intensive
treatment of patients with angioimmunoblastic lymphadenopathy with
dysproteinemia.
AB - Evolution of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) into
aggressive B cell lymphoma is thought to be a rare event and the cause of this
transformation has not been fully elucidated. We describe two patients with AILD
that progressed to aggressive large-cell lymphoma with a B cell phenotype. At
presentation, the lymph nodes of both patients showed the typical features of
AILD by hematoxylin-eosin staining. Immunohistochemical staining with monoclonal
antibodies revealed positive staining of atypical cells with UCHL-1 and negative
staining with L-26. In situ hybridization of EBV RNA showed rare positive cells
in one patient and was negative in the other patient. At relapse, both patients
showed systemic lymph nodes swelling, which is characteristic of diffuse large
immunoblastic lymphoma. Single-cell analysis with monoclonal antibodies and
immunohistochemical staining showed the monoclonal proliferation of B cells.
Southern blot analysis of the lymph nodes showed a rearrangement in both patients
of the Ig heavy chain gene and germ line configuration of the T cell receptor
beta chain gene. Southern blot analysis using the EBV terminal repeat region
probe detected clonal proliferation of EBV in the lymph nodes of both patients.
In situ hybridization studies identified considerable EBV mRNA in both patients.
These observations suggest that EBV proliferation plays an important role in the
development of B cell lymphoma that arises from AILD. We suggest that infection
or reactivation of EBV may occur in some patients with AILD, probably due to
their immunodeficient state, and that this infection or reactivation is directly
involved in the development of B cell lymphoma.
PMID- 9650456
TI - [Physical and chemical properties of vanadium and its compounds].
AB - Vanadium is present in the earth crust mainly in the heavy oils, carbons and
bituminous materials, where is associated with the heavy fractions. Many live
beings have vanadium in their tissues. Their industrial applications are
fundamentally based in the physical and chemical properties. From the
environmental point of view the vanadium emissions to the atmosphere are produced
in areas around siderurgical industries, oil refineries and cities that use
fossil fuels for heating. The pollution process in these areas is associated
partially with the presence of vanadium compounds, as is the case in the eastern
coast of the lake of Maracaibo, Venezuela. Some clinical-epidemiological
researches report a high incidence of congenital malformations at the Central
Nervous System level, and this has been associated with the intense oil
activities of the region. The high incidence of the Central Nervous System
congenital malformations could be associated with the vanadium compounds present
in the eastern coast of the lake of Maracaibo; here is the interest in the
physical and chemical properties knowledge of vanadium and their compounds.
PMID- 9650457
TI - [Role of vanadium in metabolism].
AB - The trace element vanadium, has been studied during the past few years, however
is unknown its cellular actions. This paper intends to give a review of the
different vanadium routes, its absorption, distribution, metabolism and
biotransformation, mainly because vanadium use has increased in the petroleum and
steel industries affecting their workers for its toxic effects.
PMID- 9650458
TI - [Determination of vanadium concentration in foods produced on the Eastern Coast
of Lake Maracaibo].
AB - In the northeastern coast of Lake Maracaibo it has been reported some years ago a
high incidence of congenital malformations of the Central Nervous Systems (Neural
Tube Defects Type). This epidemiological problem is present in other countries
too (Ireland and New Zealand) and has been associated with oil activities. In
fact, some experimental works inform about the vanadium compounds cellular toxic
effects mainly in the Central Nervous System of mammals. The main goal of this
work is to measure the vanadium content in foods produced in the northeastern
coast of Lake Maracaibo. Lagunillas, Valmore Rodriguez, and Baralt were the
districts selected for the work. The digestion of the samples achieved by the
methodology reported by Myron et al., with Graphite Furnace Atomic Absorption.
The amounts of vanadium in the different foods analized were higher than the
controls in the bibliographic reports. At this moment, there is not definitive
proofs that vanadium compounds are the etiological agents of the Neural Tube
Defects, but, these compounds are presents in foods produced in the northeastern
coast of Lake Maracaibo.
PMID- 9650459
TI - [Genotoxic effects of vanadium compounds].
AB - Vanadium is a metal member of the periodic table VB group, with atomic weight
59.95 and atomic number 23 and it has some oxidizing states from -1 to +5.
Vanadium has many industrial uses and its contribution with environmental
contamination is growing every day. In the last 10 years research about the
vanadium effects on living beings, has been increasing substantially, due to its
presence in the environment from different sources. Interest for vanadium and
their compounds is because its toxic effects and uses in some biomedical areas:
such as antineoplastic, cholesterol and glucose level blood, diuretic, oxygen
haemoglobin affinity. Vanadium toxic effects are so due to the fact of its
property of inhibiting many enzymatic systems. Vanadate and vanadyl ions make
chemical complexes exhibiting the property of inhibiting or increasing the
activity of the enzymes participating in the DNA and RNA synthesis. They also
induce mutagenic and genotoxic effects. Biochemical assays show cytotoxic
effects, increase in the cellular differentiation, gene expression alterations
and other biochemical and metabolic alterations. Research has been done with in
vitro systems, but few with laboratory animals. It is necessary to carry out more
work in the field of genetic toxicology with vanadium compounds. This type of
compounds may be considered mutagenic and genotoxic, with cytotoxic and
aneuploidogenous effects.
PMID- 9650460
TI - [Teratogenic effect of ammonium metavanadate in Swiss albino mice].
AB - Far as it is known to us, there is only one report in the medical literature
dealing with the teratogenous effect of vanadium on neural structures (1): while
trying to experimentally induce anencephaly in the offsprings of swiss-albino
mice through the administration of ammonium metavanadate via drinking water,
during different stages of their lives; a neural tube defect consisting of
arrhinencephaly was obtained; various degrees of hypoplasia or aplasia of both
the olfactory bulbs and tracts were evidenced, as well as congenital lesions of
variable intensity in other rhinencephalic structures. The probable mechanisms
through which vanadium exercises its neural teratogenous effect are analyzed.
PMID- 9650461
TI - [Teratogenic effects of ammonium metavanadate on the CNS of the offspring of
albino rats. A histological and histochemical study].
AB - The vanadium is a metallic oligoelement present in the majority of tissues. Its
abnormal biological disposal environment can be related with its possible
teratogenicity and alteration in the contents of glycosaminoglycans acids (GAGs),
which participate in the morphological processes and the maturation of Central
Nervous System (CNS). The proposal of the project is to analyze the teratogenic
effect of ammonium metavanadate (AMV) and its action on the GAGs in the CNS of
the litter of albino rats. The ammonium metavanadate was diluted in distilled
water in concentration of 100 and 200 ppm, drunk by the rats since their birth
and/or weaning to adult age, except during the matching and gestation. The
animals control drunk water without this metal. The litter were analyzed to
detect possible congenital malformations, then CNS were removed of descendents
and were processed by light microscope, cuts of 6 u were stained with H/E; Alcian
Blue pH 3.5 and 5.6, this last one concentrations of C12Mg from 0.05 M to until
1.0 M. Previously parallels sections were treated with testicular hyaluronidase.
The macroscopic analysis of the new born rats that came from rats that received
AMV in concentrations 100 and 200 ppm, resulted in congenital anomalies like
unilateral hypoplasia of olfactory bulbs and cerebral hemisphere. The microscopic
analysis revealed changes in the layers patron of olfactory bulbs and an
increased of alcianophilia in the pH 5.6 to 0.2 M MgC12, in the extracellular
matrix of CNS of rats descendents treated with AMV to the dose 200 ppm, sensibles
to the testicular hyaluronidase, corresponding to hyaluronic acid (HA) and
chondroitin 4 and/or 6 sulphate (C4S or C6S) of low grade of sulphation. These
results suggest that the AMV given to albino rats has a teratogenic result when
it is used before the gestation and for long periods of animals life that alter
the of GAGs of CNS contents during the development.
PMID- 9650462
TI - [Toxic effects of ammonium metavanadate on the growth and number of the offspring
of Swiss albino mice].
AB - The present research show, an statistical study of the effects of ammonium
metavanadate (AMV) on size, weight and number of offsprings of 56 albino swiss
mice (male and female) was carried out. These mice ingested AMV in concentration
of 100 and 200 ppm "ad libitum" since birth, continuing throughout breasting
until mating. The control group received water free from the metal. The
statistical results, obtained by the Duncan and Tukey method, were the following:
a significant drop in body size in 200 ppm concentration of AMV, and in tail size
in a concentrations of 100 and 200 ppm. A significant increase was observed in
the number of the offsprings on the groups treated with AMV on a concentration of
200 ppm with respect to the control group.
PMID- 9650463
TI - [Changes in female reproduction induced by ammonium metavanadate in Swiss albino
mice].
AB - Female reproduction alterations induced by vanadium salts, taken in periods no
related with mating/gestation, correlated with histological alterations has not
been reported. Vanadium is a metal from VB group of periodical table, and it has
been detected in high concentrations in heavy petroleum produced in this region
of our country, there have not had investigations about vanadium effect on
species reproduction. In this work 100 and 200 ppm doses of ammonium vanadate
(A.M.V.) prepared with demineralized water were administered orally to swiss
albino mice in different periods. The administration of vanadium salt was
suspended before mating. Pregnant mice were allowed to deliver and a statistical
analysis were performed to pregnancy percent and pups means. Non pregnant mice
were killed after 21 days of mating. Uterus and ovaries were weight, luteal
bodies were counted and histological samples of ovaries were prepared. The
results shown a non significative increase of pregnancy (p < 1) in mice exposed
from weaning to adult, for animals exposed to maximum concentrations 200 ppm a
significative reduction of pregnancy (p = 0.00001), to mean pups were detected (z
= 0.68), and number of luteal bodies (s = 3.3 +/- 0.5). The microscopic
observation shown polycystic ovary, atresic follicular increasing, follicle in
mature stage and luteal bodies; hard decreasing; hard depletion was observed in
thecoluteic cells of luteal bodies. A.M.V. modify reproduction even though if
exposition have been made in period before mating and pregnancy. As doses and
exposition periods increase detrimental effects induces alteration in the
follicular phase and luteal of ovarian cycle. Epidemiological and genetic studies
are recommended in regions where vanadium concentrations are high, and the
drinking water and foods are contaminated with this metal, in order to know how
it affect human reproduction.
PMID- 9650464
TI - [Genotoxic effects of vanadyl sulfate in Drosophila melanogaster].
AB - This study presents the analysis of chemically induced somatic mutation in
Drosophila larvae assayed later as single light (LS) mosaic spots in the adult
eye. The larvae were treated with Vanadyl sulphate (VOSO4), the highest exposure
was 10.0, 8.0, 6.0 and 4.0 mM which was the acutely lethal concentration, while
than lowest exposure of 2.5, 2.0 and 1.0 mM, cause reproductive effects and
genotoxic activity, compared to the control. Previous to the realization of the
mutagenicity assay was determined the lethal toxicity of the compound undertest
since the concentration-mortality relationship is a useful indicator of the
biological activity of Vanadium. The toxic effect in fly adult was to compare any
differences in the sensitivity of males (white) and female (oregon), observing
the higher sensitivity of the males. The date presented with tests SMART and
their statistical evaluation lead to the following conclusions. To test the two
hypotheses was propose to apply the conditional binomial test (Kastenbaum and
Bowman, 1970) or the X2 test for proportions (K. Pearson criterion). Each
hypothesis was tested at the 5% significance level. In conclusion the Vanadyl
Sulphate produce aberrant red sector in w+/w, it is not correlated with the
capacity of an agent to induce chromosomal damage and mitotic recombination, but
rather seems positively correlated with its weak capacity to produce points
mutations.
PMID- 9650465
TI - Fifteen years' experience with gastric partitioning for obesity treatment.
AB - Most reports derived from experiences in Western countries indicate that surgery
offers the best hope for morbidly obese patients. We report our experience with
gastric partitioning in 63 Chinese patients (17 men and 46 women) aged 14 to 42
years, whose preoperative excess weights ranged from 62.3% to 166.7% above their
ideal body weight. Transverse stapling was performed in 30 patients treated
before April 1983, while vertical stapling gastric partitioning with a window and
a Marlex band to encircle the outlet tract was done in 33 patients after that. No
patient died, but one had leakage at the anastomosis. Success was defined as a
return to within 50% of the ideal body weight. Vertical-windowed gastric
partitioning with a Marlex-banded outlet resulted in a significantly higher
success rate than transverse stapling--70% vs 37%. Our experience suggests that
vertical-windowed gastric partitioning with a Marlex-banded outlet is a safe and
effective surgical treatment for morbidly obese Chinese people.
PMID- 9650466
TI - Urinary endothelin-1 in children with acute renal failure of tubular origin.
AB - To understand the changes of urinary endothelin-1 (ET-1) concentrations in acute
renal failure (ARF) and to investigate the origin of human urinary ET-1, we
studied urinary ET-1 excretion in 70 normal children and 12 children with ARF
caused by tubular dysfunction. Urinary ET-1 excretion was expressed as a ratio of
urinary ET-1 to urinary creatinine (ET-1/Cr). Among healthy children, the highest
urinary ET-1/Cr values were found during infancy. In patients with ARF, there was
a positive correlation between urinary ET-1/Cr values and daily total urinary ET
1 (r = 0.42, n = 26, p < 0.05). Plasma ET-1 concentrations were elevated in
children with ARF during the period of peak serum creatinine concentration.
During the course of ARF, the lowest urinary ET-1/Cr value occurred during the
period of peak serum creatinine, whereas the plasma ET-1 concentration declined
after the peak. These results provide insight into the developmental changes of
urinary ET-1 values in normal children, and illustrate the pattern of changes in
plasma and urinary ET-1 concentrations during the course of ARF in children. The
results suggest that renal production, rather than clearance from the circulation
by glomerular filtration, may be the source of urinary ET-1.
PMID- 9650467
TI - Liquid ventilation for treatment of meconium aspiration syndrome in a piglet
model.
AB - We tested the hypothesis that liquid ventilation (LV) with perfluorocarbon (PFC)
can remove aspirated meconium and improve lung function in experimental meconium
aspiration syndrome (MAS). PFC (FC-77) was used as the medium in LV. Sixteen
piglets were divided into control and LV groups (8 animals/group). All animals
received slurry meconium (20% in normal saline) via endotracheal instillation at
baseline. Thirty minutes later, the LV group received 15 cycles of LV. Pulmonary
mechanics, arterial blood gases, and hemodynamic values were recorded at
baseline, and 30, 60, 120, 180, and 240 minutes after meconium instillation.
Chest radiographs and lung sections were taken and scored at the end of the
study. The percentage of meconium cleared by LV was calculated as the ratio of
the dry weight of washings to that of meconium instilled, multiplied by 100. The
procedure was tolerated well by the animals. LV cleared 25% +/- 7% of the
instilled meconium. Tidal volume (9.5 +/- 2.0 vs 7.1 +/- 0.8 mL/kg, p = 0.012),
respiratory system compliance (2.32 +/- 0.60 vs 1.60 +/- 0.24 mL/cmH2O, p =
0.01), PaO2 (65 +/- 7 torr vs 55 +/- 6 torr, p = 0.0067), and arterial to
alveolar oxygen ratio (0.14 +/- 0.01 vs 0.12 +/- 0.01, p = 0.0077) were improved
in the LV group at 60 minutes after meconium instillation compared with those of
the control group. The scores of exudative debris (1.7 +/- 0.3 vs 2.1 +/- 0.2)
and visible meconium (1.4 +/- 0.5 vs 2.1 +/- 0.5) were significantly lower in the
LV group. In conclusion, short-term L.V with FC-77 can partially remove aspirated
meconium from the lungs and improve pulmonary function transiently.
PMID- 9650468
TI - Dideoxy fingerprinting for rapid screening of rpoB gene mutations in clinical
isolates of Mycobacterium tuberculosis.
AB - Rifampin is a key component of therapeutic regimens for tuberculosis control, and
a marker for multidrug resistance of Mycobacterium tuberculosis. Mutations
responsible for conferring rifampin resistance in M. tuberculosis are known to
occur in a 69-bp region of the rpoB gene. In this study, we assessed the accuracy
of dideoxy fingerprinting (ddF), a hybrid technique employing elements of dideoxy
sequencing and single-strand polymorphism analysis, for rapid screening of
rifampin resistance in clinical isolates of M. tuberculosis. This technique was
used to analyze 72 M. tuberculosis isolates. The results were compared with those
of automated dideoxy sequencing and the antibiotic resistance profile (determined
with the BACTEC system). Of the 72 isolates, 50 were rifampin resistant. The ddF
findings were completely consistent with those of dideoxy sequencing in all
isolates. In 68 (94%) isolates, the ddF findings were consistent with the
rifampin resistance status determined with the BACTEC system; all four isolates
with inconsistent results had no mutation in the 69-bp region, but were resistant
to rifampin. Our findings suggest that ddF accurately detects mutations in the
rifampin resistance-associated 69-bp region of the rpoB gene in clinical isolates
of M. tuberculosis, and may be a valuable screening tool for rifampin resistance.
PMID- 9650469
TI - Bacteremia in patients with hematologic malignancies.
AB - The decision regarding the appropriate empirical antibiotic therapy for
bacteremia in patients with hematologic malignancies must be individualized in
each institution, by taking into account variations in the patterns of microbial
isolates and their resistance profiles. Microbial isolates and antibiotic
resistance patterns must be taken into account at each hospital. A shift from
bacteremia due to infections caused by predominantly gram-negative organisms to
predominantly gram-positive organisms in patients with hematologic malignancies
has been noted in reports from other countries. We investigated bacterial
isolates and their antibiotic sensitivities in patients with hematologic
malignancies in the Veterans General Hospital-Taipei. A total of 185 episodes of
bacteremia in 140 patients with hematologic malignancies were recorded during the
period from 1995 to 1996. Unlike foreign reports, our investigation shows that
gram-negative organisms still predominate, accounting for 72.7% of isolates,
followed by gram-positive organisms, accounting for 26.3% of isolates, and
anaerobes, accounting for 1% of isolates. Escherichia coli was the most commonly
isolated organism, accounting for 23.9% of isolates, followed by Klebsiella
pneumoniae (18.5%), Pseudomonas aeruginosa (12.2%), Enterobacter cloacae (7.3%),
and methicillin-resistant Staphylococcus aureus (7.3%). A high mortality rate was
observed in gram-negative bacteremia: 31% for E. coli, 26% for K. pneumoniae, 24%
for P. aeruginosa, and 33% for E. cloacae. If methicillin-resistant S. aureus
bacteremia occurred, mortality was high (47%). The antibiotic sensitivity
profiles of the four most common gram-negative isolates (E. coli, K. pneumoniae,
P. aeruginosa, and E. cloacae) indicated that, in our hospital, amikacin with
either cefoperazone, ceftazidime, ciprofloxacin, or imipenem, would be an ideal
combination for empirical therapy for bacteremia in patients with hematologic
malignancies.
PMID- 9650470
TI - Hybrid total knee arthroplasty: a 3- to 6-year outcome analysis.
AB - We retrospectively analyzed the outcomes of hybrid total knee arthroplasty (TKA)
with Miller Galante I (MG I) prostheses in 113 consecutive patients (140 knees).
The mean follow-up period was 4.8 years (range 3.2-6.6). There were 135 cases of
osteoarthritis and five of rheumatoid arthritis. The average age of patients at
the time of surgery was 62.6 years. The Hospital for Special Surgery knee score
along with radiographs were used to evaluate preoperative and postoperative knee
status, and the Cybex isokinetic test was used to assess muscle strength at the
final follow-up. The average knee score improved from 64 points preoperatively to
90 points postoperatively (p < 0.05). The mean motion are of the knee improved
from 108 degrees preoperatively to 116 degrees at the final evaluation. A total
of 122 knees were pain free on walking and 130 knees were completely pain free at
rest. A total of 134 knees achieved good to excellent clinical results. The
radiographic results showed that the mechanical axis of the lower extremity was
realigned from a mean of 12 degrees varus preoperatively to a mean of 1 degree
varus postoperatively. No obvious radiolucent zones were found on the lateral
view of the femoral components in 60.7% of the knees, or on the anteroposterior
or lateral views around the tibial components in 49.3% and 82.9% of knees,
respectively. The Cybex isokinetic test at the final follow-up examination
revealed that the hamstring/quadriceps peak torque ratio was 0.8 at a speed of 60
degrees per second and 0.96 at 180 degrees per second, indicating that quadriceps
muscle strength did not recover to within the range of healthy subjects. There
were 23 (16.4%) complications, including polyethylene wear of patellar components
(14), patellofemoral maltracking (4), septic loosening (2), aseptic loosening
(2), and superficial infection (1). Revision surgery improved the functional
outcomes in all of these knees. Based on our experience, we do not recommend the
use of the MG I prosthesis in total knee arthroplasty (TKA) because of the high
rate of patellar complications. Strengthening of the quadriceps must be
emphasized in postoperative rehabilitation. Hybrid fixation might be a useful
alternative fixation mode in TKA procedures.
PMID- 9650471
TI - Evolution of dilated cardiomyopathy from hypertrophic obstructive cardiomyopathy
in a child.
AB - Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are two
different diseases and have distinct etiologies. HCM is rare in children and
rarely progresses to DCM. We report a 5-year-old Taiwanese girl with a definite
diagnosis of hypertrophic obstructive cardiomyopathy. The diagnosis was based on
echocardiograms, cardiac catheterization, and endomyocardial biopsy. However, the
clinical features progressed to a picture of nonobstructive HCM at age 9, and the
patient developed dilated poorly contractile ventricles with intractable
congestive heart failure at age 10. She died from ventricular tachycardia at age
13. This report emphasizes the importance of periodic reevaluation for children
with HCM.
PMID- 9650472
TI - Response of Epstein-Barr virus-associated Ki-1+ anaplastic large cell lymphoma to
13-cis retinoic acid and interferon alpha.
AB - The response of peripheral T-cell lymphoma to 13-cis retinoic acid (13-cis-RA)
has been well established, especially in Ki-1+ anaplastic large cell lymphoma
(ALCL) confined to the skin. Here, we report the use of 13-cis-RA in combination
with interferon alpha in a patient with refractory ALCL. The patient, an 18-year
old man, suffered from retroperitoneal, hepatic, and splenic ALCL. Reactive
hemophagocytic syndrome also developed. Active Epstein-Barr virus infection was
demonstrated by serologic tests and in situ hybridization of Epstein-Barr virus
early RNA-1. Although high-dose intravenous immunoglobulin (IgG), etoposide, and
steroids were administered, only chemotherapy (methotrexate, bleomycin,
doxorubicin, cyclophosphamide, vincristine, and dexamethasone) successfully
controlled the progress of hemophagocytosis. However, the retroperitoneal mass
and splenic tumor did not show a satisfactory response to three cycles of
chemotherapy. Hence, interferon 4.5 MU/m2 every other day with 13-cis-RA 1
mg/kg/day was instituted. Abdominal computed tomogram after 58 days of treatment
revealed that the tumor had significantly reduced in size. Bone marrow biopsy
demonstrated alleviation of hemophagocytosis as well. However, lymphoma cells had
begun to infiltrate the bone marrow. Our findings suggest that 13-cis-RA and
interferon alpha may be partially effective in treating ALCL.
PMID- 9650473
TI - Conjunctivitis caused by Thelazia callipaeda infestation in a woman.
AB - Thelazia is a nematode (Spirurida) that can parasitize the mammalian conjunctival
sac. This is the first reported case of ocular. Thelazia callipaeda infestation
in Taiwan. A 41-year-old woman experienced swelling, itching sensation and
occasional blurred vision of the right eye 2 weeks after a small group of flies
swarmed her eye while she was hiking. Her symptoms were first misdiagnosed as
allergic conjunctivitis at a local medical clinic. During her first visit to our
outpatient department, five white thread-like living worms were discovered on the
superior and inferior fornices. The worms were cream-colored, slender and
approximately 1 cm in length. Follicular and papillary conjunctivitis was noted
in her right eye. After removing the worms, the symptoms resolved and no other
worms were found in the following 2 months. This case is a remainder to
physicians that parasitic infestation should be included in the differential
diagnoses of ocular itching, conjunctivities, and blurred vision after insect
contact.
PMID- 9650474
TI - Regional nerve block for total knee arthroplasty.
AB - Femoral and sciatic nerve blocks have been used occasionally for unilateral total
knee arthroplasty (TKA). In order to evaluate the effectiveness of this
technique, combined femoral 3-in-1 and sciatic nerve blocks were performed in 20
cases of TKA, by the same surgeon. This surgeon also performed unilateral TKA
under spinal anesthesia in another 20 cases. The anesthetic effectiveness of the
two types of anesthesia was compared in terms of the time needed to complete the
surgery, amount of intraoperative blood loss, and time interval until the first
dose of analgesic. The results showed that the two types of anesthesia had
comparable anesthetic effects. Ten of the 20 patients who had spinal anesthesia
complained of postoperative urinary retention, while none of those who had nerve
block had this complaint. Neither group experienced postpunctural headache,
neurovascular damage, or drug-over-dose toxicity. We conclude that combined
femoral 3-in-1 and sciatic nerve block is an effective anesthetic alternative for
unilateral TKA.
PMID- 9650475
TI - Adrenal extramedullary hematopoietic tumor in a patient with beta-thalassemia.
AB - We report a case of adrenal extramedullary hematopoiesis in a 27-year-old woman
with beta-thalassemia. She underwent cholecystectomy for gallstones and
splenectomy for splenomegaly at the age of 20 years. In January 1996, she was
admitted to our hospital because of a palpable nontender mass in the right
subcostal area. Ultrasound, computed tomography, and magnetic resonance imaging
disclosed a right suprarenal mass 7.5 x 5.8 cm in size. Surgical exploration and
biopsy confirmed the diagnosis of extramedullary hematopoietic (EMH) tumor. The
tumor was left in situ. Subsequent follow-up showed no increase in the size of
the tumor and no progression of anemia. The patient remained asymptomatic, and no
additional EMH tumor developed. Surgery or radiotherapy should be performed only
when EMH tumors cause symptoms, such as during spinal cord compression. Adrenal
EMH tumors should be considered in thalassemia patients with an adrenal mass, to
avoid unnecessary surgical procedures.
PMID- 9650476
TI - [Surgical treatment of war injuries of the veins].
AB - Between April 1991 and December 1995, 118 patients were treated for wartime
venous injuries. There were 108 (91.5%) venous injuries combined with arterial
ones, and 52 (49%) with bone fractures. A total of 85 (72%) venous repairs were
done and 33 (27.9%) were treated by ligation. Arteriovenous fistulas were found
in 20 (16.9%) venous injuries. Venous injuries were associated with 10 (62.5%)
amputations and 5 (45.4%) deaths. In the early postoperative period the authors
found 15 (17.6%) thromboses of venous reconstructions.
PMID- 9650477
TI - [Prognostic value of determination of the presence and histologic grade of the
intraductal component in invasive ductal carcinoma of the breast after
conservative treatment].
AB - In recent years, breast-conserving therapy and radiation therapy have become an
important treatment option for patients with stage I and II invasive breast
cancer. The results of long-term retrospective studies have demonstrated that
this treatment can provide a high level of local tumor control with satisfactory
cosmetic results. Numerous studies have shown that the presence of extensive
intraductal component (prominent intraductal carcinoma) is highly associated with
subsequent local recurrence. In this article we have stressed the value of the
determination of the presence and the histologic grade of prominent intraductal
component of invasive ductal breast carcinoma in the determination of the extent
of surgery. We also point out the possibility of determination of prominent DCIS
on frozen sections.
PMID- 9650478
TI - [Acute respiratory infection in general clinical practice].
AB - Due to high frequency, certain risk of related complications, absenteeism, direct
and indirect costs related to them, acute respiratory infections represent a
significant health problem. The aim of the paper is to examine the frequency and
characteristics of acute respiratory infections, as well as the characteristics
of patients with these infections among the population in care of general
practitioners/family physicians. In 11 teaching general practices in Zagreb, data
were collected from medical records on patients and acute respiratory infections
which the patients developed over the period from October 1, 1994 to September
30, 1995. For statistical data processing description, distribution analysis and
chi-square test were used. Out of 17,888 patients in care of general
practitioners involved in the study, acute respiratory infections were noticed in
4,114 (22.9%) patients ranging in age from newborn to 97 years out of which 1,473
(35.8%) were males and 2,641 (64.2%) were females. A total of 5,892 acute
respiratory infections were observed, in average 1.43 infections per patient, for
which the patients visited their general practitioners 11,610 times (1.97 visits
per infection). Most of the patients 2,958 (71.9%) attended their general
practitioners because of one acute respiratory infection. The initial diagnosis
of acute upper respiratory tract infection was registered in 4,601 (78.1%)
infections, and final diagnosis in 4,475 (75.9%) infections. The most frequent
diagnoses included: pharyngitis and tonsillitis (including streptococcal
pharyngitis and tonsillitis), nasopharyngitis, sinusitis and bronchitis. In 4,874
(82.7%) cases, general practitioners based their diagnosis on patient history and
clinical examination. Antibiotics were prescribed in 3,892 (66.1%) cases. Out of
42 (1.2%) patients treated in hospital, seven patients were admitted for
tuberculosis and two for bronchi cancer detected during the acute respiratory
infection. Follow-up was reported in 3,644 (60.3%) cases, and sick leave in 1,236
(31%) cases. The results of this study have shown significantly higher frequency
of acute respiratory infections in the morbidity in outpatient health care, and
also that management of patients with these diseases is mainly the responsibility
of general practitioners. In order to improve professional competence of general
practitioner/family physician and quality of work in the management of patients
with acute respiratory infections in general practice/family medicine, it is
necessary to continuously improve the knowledge on all characteristics of the
management of patient with these diseases in general practice, as well as to make
a critical assessment of the existing practice.
PMID- 9650479
TI - [Comparison of the convergence:accommodation ratio in amblyopes treated with
various pleoptic methods].
AB - C:A ratios were tested in 50 amblyopes healed by methods of penalization and in
50 amblyopes healed by classic pleoptic methods. C:A ratios were same for both
groups of subjects, so both methods of treatment can be applied in this sense.
PMID- 9650480
TI - [First degree atrioventricular block caused by a calcified tumor of the
atrioventricular septum].
AB - First degree atrioventricular block occurred in a 69-year-old patient with a
calcified atrioventricular septum tumour. The patient suffered several episodes
of syncope and the only abnormality found in the routine clinical work-up was a
remarkable first degree atrioventricular block. The echocardiogram, computed
tomography (CT) and the magnetic resonance imaging (MRI) procedure showed a
calcified tumour in the posterior part of the left ventricle, between the left
atrium and left ventricle, just beneath the aortic root spreading to the
interventricular septum. It was suggested that the first degree atrioventricular
block was caused by the tumour. The symptoms were relieved by implantation of
permanent cardiac pacemaker.
PMID- 9650481
TI - [X-linked adrenoleukodystrophy--2 case reports].
AB - Cases of a ten-year-old boy with childhood cerebral adrenoleukodystrophy (ALD)
and a 22-year-old youngster with adrenomyeloneuropathy (AMN) are reported. ALD is
an inherited, X-linked perixisomal disorder associated with the accumulation of
very long chain fatty acids (VLCFA). Neurological symptoms occur due to
progressive demyelination and destruction of cerebral white matter and primary
adrenal insufficiency. The boy with ALD manifested neurological signs (impaired
spatial orientation, visual disturbances, poor handwriting, seizures). Latent
primary adrenal insufficiency was established, and successfully treated by gluco-
and mineralocorticoids. Lorenzo's oil (mixture of
glyceroltrioleate:glyceroltrierucate 4:1) treatment significantly reduced
elevated concentrations of VLCFA, but in spite of that, neurological symptoms
progressed and the boy died a year after the initial clinical presentation of the
disease. The boy with AMN revealed primary adrenal insufficiency at the age of 15
years. AMN was suspected when hair and eyebrows loss occurred and the diagnosis
was established due to elevated VLCFA levels in the serum at the age of 22 years.
On examination no neurologic signs of the disease could be detected. Adrenal
insufficiency is well controlled by gluco- and mineralocorticoids. In addition to
the previously described two women who were symptomatic heterozygotes we now also
report on two patients with ALD and AMN. The patients reported are the first four
with this peroxisomal disorder described in Croatia so far. Probably a great
number of such patients remains unrecognised. Therefore, it is necessary to
measure the serum VLCFA levels in males with primary adrenal insufficiency, and
in those with signs of progressive central demyelination and destruction of
cerebral white matter accompanied by neurological symptoms of unknown etiology.
PMID- 9650482
TI - [Injuries in the etiopathogenesis of multiple sclerosis].
AB - An injury might derange the protective function of the blood-brain barrier, and
thus it represents one of the possible pathogenetic factors in the demyelination
of the neural axis. However, the effect of injury on the occurrence or
deterioration of multiple sclerosis is still controversial. According to most
authors, the importance of injury in individual cases of multiple sclerosis is
undeniable, as well as the fact that injuries are factors of progression and
deterioration of the disease, but never its cause. Consequently, injuries can
cause only temporary disability, and not permanent. Nevertheless, the incidence
of multiple sclerosis increases proportionally to the severity of injury. The
length of the period from the occurrence of injury to possible demyelination is
still not established. Studies and clinical reports point to the fact that in the
evaluation of injury as a precipitating factor for the vulnerability of the blood
brain barrier, the severity of the injury is of greater importance than its site.
PMID- 9650483
TI - [The respiratory system--its self-cleaning system. General mechanisms of
clearance].
AB - The behaviour of particles and deposition in different parts of respiratory
system are described. Listed are factors which contribute to the deposition of
particles in the lungs and upper areas of the respiratory system. The general
mechanisms of lung clearance and their action such as cough, mucociliary
transport, alveolar clearance and immunological system are reported. Particularly
is stressed the necessity of coordination of all defense mechanisms in order to
maintain normal respiratory function.
PMID- 9650484
TI - [Paraneoplastic autoimmune neurologic syndromes].
AB - Paraneoplastic neurologic syndromes are group of distant nonmetastatic neurologic
manifestations of malignant diseases. In last few decades a major advance in
understanding their etiology and pathogenesis has been achieved. Larger series of
patients have been reported allowing more detailed clinical research of
particular syndromes. To practicing physician they can be a first clinical sign
in diagnosing a neoplasm. In these conditions immunologists can test new theories
in tumor immunology and autoimmunity. To the oncologists they can serve as a
model in development of new modalities of treating malignant tumors. Neurologic
syndromes that can be explained as autoimmune reactions initiated by the
development of malignancy are presented in this paper.
PMID- 9650485
TI - [Group psychotherapy in the treatment of post-traumatic stress disorder].
AB - Working with psychotraumatized war veterans we perceived their extremely
regressive position, which is accompanied by several destructive and
autodestructive compulsions. Facing the multiple traumatic experiences which they
lived through, a certain degree of regression has been appearing, since even a
satisfying "nourishing-indulgence of their needs" cannot completely make up for
their pre-war position. In this way occurred the splitting between ideal
(introjected) object and real object, in which were projected all bad
experiences, and which is still persecuting and wants to destroy. Through
interactions between all group members of traumatized patients we analyzed the
phenomena and the specificities of these groups-particularly their regressive
position. The aim of the group psychotherapy was to enable progressive overcoming
of regressive position and transition into a more mature stage of development,
thus creating a favorable climate for growing up and independence.
PMID- 9650486
TI - [In memory of Dr. Danko Riessner].
PMID- 9650487
TI - Schools misinterpret immunization rules.
PMID- 9650488
TI - Court rules insurer employee was practicing medicine.
PMID- 9650489
TI - The liquidation of PIC and PIE: what physicians need to know.
PMID- 9650490
TI - Should medications be crushed?
PMID- 9650491
TI - Delaware Valley organ donation system is national model.
PMID- 9650492
TI - [The future of immunology and clinical allergy in Mexico].
PMID- 9650493
TI - [Oropharyngeal bacterial flora in asthmatic and health subjects].
AB - MATERIAL AND METHODS: It was carried out cultivation of oozing pharyngeal to 248
fellows, 128 of them were asthmatic and 120 seemingly healthy. From group of
asthmatic 55.46% they correspond to the masculine sex and 44.54% to the feminine;
72.97% they present more than two sharp squares of asthma per month. RESULTS: In
the cultivation of 107 asthmatic the presence of germs is reported like:
Staphylococcus aureus positive 43.56% (p = NS), the Streptococcus betahemolytic
72.97% (p = 0.001), Candida albicans 70.58% (p = 0.004), Streptococcus alpha
haemolyticus 61.42% (p = 0.008). CONCLUSIONS: When they exist more than two germs
in a same individual frequently the Staphylococcus aureus is detected with the
Streptococcus beta hemolytic 42.10% or with the Candida albicans 31.57%. We
proposes to magnify the problem to which the patients face in order to order a
medication or examine of laboratory with opportunity and when we hoped to obtain
the good benefit for the health of the population.
PMID- 9650494
TI - [Comparison of 4 skin prick tests to detect immediate hypersensitivity].
AB - AIMS: To diagnostic allergic diseases it's necessary an adequate history, and in
vivo or in vitro test, to determine specific IgE. The skin prick test are the
best for this, because are more sensitive, economic and quick to do. However
there are variability in results with the different instruments to do it (the
Morrow-Brown (MB), needle, Prick lancet (L)t Multi-Test (MT), and the Doutip
Test). To consider this instruments how adequate diagnostic proceedings, we
should evaluate some characteristics. Because it, our objective was to evaluate
precision, sensitivity, specificity and patient preference by each one. METHOD:
Prospective study in 20 patients with asthma or allergic rhinitis who comes to
the allergy service of Hospital Infantil de Mexico Federico Gomez. We analyzed
skin prick test with DT, MB, MT and L on the back surface with histamine in five
times and glicerosaline in one. We measured wheel and flare diameters 15 minutes
after applications. We consider positive results if medium diameter of wheel was
3 mm or flare 10 mm. Precision was measured by coefficient of variation of wheel
with histamine with each instrument. Patient preference was considered in
relation to low grade of discomfort with each one. Precision was compared by two-
vias varianza analysis. No parametric Friedman test was used to compared patient
preference. RESULTS: We studied 20 patients, 40% was females and 60% males. The
ages were 10 to 16 years old Promedio wheal histamine diameter was to MB = 5.1 +/
1.1, L = 6.1 +/- 0.8, DT = 6.7 +/- 0.9, MT = 6.3 +/- 1.5; promedio flare
diameter with histamine was to MB: 15.9 +/- 4.2, L: 19.0 +/- 4.8, DT = 21.9 +/-
4.8, MT = 18 +/- 6.9. Sensibility of DT was 100%, L = 99%, MT = 97% and MB 95%.
The specificity of MB was 90%, L = 70%, MT = 41.6% and DT 30%. DT coefficient of
variation was 15.6%, L: 17.3%, MT = 24.4% and MB 24.6%. CONCLUSIONS: In our study
more sensitive device was DT, more specific was MB and more precise was DT.
Patients preferred the lancet, because they had less discomfort when used it.
PMID- 9650495
TI - [Effect of levamisole on microbicidal activity and chemotaxis in
polymorphonuclear cells].
AB - AIMS: Neonatal septicemia may have a mortality of 20% in newborns small for their
gestational age. This susceptibility for infections has been explained by
immunological disorders. The aim of this study to know the effect of levamisole
on the functions of chemotaxis and bacterial activity of PMN cells in newborns
small for their-gestational age. MATERIAL AND METHODS: Twenty full-term newborns
were studied. Ten of them were small for their-gestational age, and the other 10
had body weight within the normal range. Microbicidal activity and chemotaxis
were measured, and comparisons between groups were made with non-parametric
statistical tests. RESULTS: In the group of newborns small for their-gestational
age. Microbicidal activity was similar to control group, but chemotactic activity
was reduced (p < 0.05).
PMID- 9650496
TI - [Development of a questionnaire to assess the knowledge on infantile++ asthma in
medical students].
AB - Asthma is the most common chronic childhood illness. The increasing morbidity and
mortality are striking contrast to major scientific advances in our understanding
of asthma. It is now regarded as a chronic rather than a episodic illness and the
major factors contributing to asthma morbidity and mortality are underdiagnosis
and inappropriate treatment. The majority of children with asthma are cared for
by nonspecialist physicians. Studies have shown that only small proportions of
practitioners have an adequate understanding of the changing concepts of asthma
management. We development an asthma knowledge questionnaire based on "Guidelines
and the Practice Parameters for the Diagnosis and Management of Asthma" of The
National Heart, Lung, and Blood Institute. The questionnaires include 25
questions on definition, physiopathology, diagnosis and treatment.
PMID- 9650497
TI - [Kartagener syndrome (type 1 primary ciliary dyskinesia). Report of a case and
review of the literature].
PMID- 9650498
TI - [A single-center controlled clinical study with Sandimmune Neoral after kidney
transplantation].
AB - The authors compared in a controlled clinical study two groups of patients after
a first renal transplantation treated by triple drug immunosuppressive therapy.
In a group of 31 patients the triple combination comprised Sandimmune Neoral. In
the control group there were 30 patients who received Sandimmune. No differences
were found between the two groups as regards the effectiveness of this treatment
and the authors did not confirm a lower incidence of rejections described in
patients treated with Sandimmune Neoral. They confirmed, however, a lower
interindividual variability of Cy-A levels assessed specifically in patients
treated with Sandimmune Neoral.
PMID- 9650499
TI - [The effects of Carvedilol, a beta-blocker, in experimental ischemia-reperfusion
kidney injury].
AB - Carvedilol is a recently introduced drug with multiple action with a non
selective beta-antiadrenergic and selective alpha1-antiadrenergic action used for
treatment of mild to medium severe hypertension. The authors investigated in
their experiments the protective effect of carvedilol under conditions of
ischaemia-reperfusion of the kidney in the laboratory rat. The animals were
divided into four groups 1. the control group was fed a diet without carvedilol
for a period of two weeks. Groups 2, 3 and 4 were fed for two weeks a diet
containing carvedilol, 1-3-10 mg/kg/day resp. After completed medication in all
animals ischaemia of the kidney was induced (60 min.) with subsequent reperfusion
(10 min.) Then the animals were sacrificed, the kidney was removed for
histopathological examination, in blood the malondialdehyde (MDA) level was
assessed. The conclusions of the investigation indicate a marked protective
effect of the administered preparation. Carvedilol prevents the disintegration of
tubular epithelia, pycnosis of the nuclei, and reduced the development of
oedematous changes. These findings correlate with MDA levels.
PMID- 9650500
TI - [Analysis of perception in patients during an acute attack of bronchial asthma].
AB - An analysis of subjective sensations during an asthmatic attack in 51 asthma
patients was performed. A difficult inspiration or inspiration and expiration was
the most prevalent sensation, while isolated difficult expiration was only sparse
finding. A tightness on the chest was often noticed as well. The probable
explanation for these observation could be the breathing a high lung volume
(hyperinflation), caused by closing small airway a mostly due to
bronchoconstriction during the asthmatic attack. The authors suggest not to
generally use the term "expiratory breathlessness" when describing the clinical
picture of an asthmatic attack.
PMID- 9650501
TI - [Levels of CK MB mass in patients with acute myocardial infarct treatedwith
fibrinolysis. Comparison with levels of CK, CKMB, CKMB mass and troponin T in the
diagnosis of coronary ischemia].
AB - In a group of 26 patients with AIM the CKMB value was raised above the
discrimination level already on admission--on average 2.7 +/- 1.4 hours after
development of ischaemic pain--in 46% patients. The maximal value of CKMB mass
was achieved in the group with probable reperfusion 12.1 +/- 3.8 hours after the
development of ischaemic pain and this value was elevated in relation to the
discrimination value 41.5 +/- 17x and in relation to the so-called basal value
145 +/- 117x. In the group without probable reperfusion the maximal value was
achieved significantly later, after 19.8 +/- hours and was elevated in relation
to the discrimination value 31 +/- 17x and in relation to the final value 84 +/-
42 times. The value of CKMB mass increased above the discrimination limit from
the onset of ischaemic pain after 4.0 +/- 1.5 and after 5.7 +/- 3 hours in the
group with probable and without probable reperfusion and declined below the
discrimination limit after 00 +/- 60 and 119 +/- 98.0 hours in the same groups.
On comparison of CK, CKBM, CKBM mass and troponin T on admission the CKMB mass
value was elevated in 46% patients, the value of CK in 23%, of CKMB in 27% and
the troponin T value in 96% patients. With regard to the assembled experience
that haemolytic serum raises false troponin T values, the percentage of elevated
troponin T values on admission declines from the original 96% to 81% when all
haemolytic samples are eliminated. The time of reaching maximal values of CKMB
mass in patients with AIM and probable reperfusion was significantly shorter than
in CK values and is similar as in CKMB values. The time taken to raise the CKBMB
mass value above the discrimination value is significantly shorter than the time
taken by CK levels, but significantly longer than the time before troponin T
levels are raised. The time of total elevation of CKMB mass levels above the
discrimination limit does not differ from the time taken to raise CK values, it
is however shorter than the increase of troponin T values, although the exact
time of persistence of raised levels of troponin T was not assessed in our work.
The time of increase above and decrease below the discrimination limit was not
assessed in CKMB values. Based on mutual comparison of the impact of indicators
for assessment of the diagnosis of ischaemic heart attacks the authors consider
it best regardless of financial costs--to assess troponin T, possibly along with
levels of CKMB mass.
PMID- 9650502
TI - [The effect of 4 years' of hypolipemic treatment on the width of the common
carotid artery intima in patients with familial hyperlipidemias].
AB - Sixty-four patients with familial hyperlipoproteinaemia were treated for almost
four years by dietetic treatment and various hypolipidaemic drugs. In 25 patients
with familial hypercholesterolaemia who had clinical signs of ischaemic heart
disease total and LDL-cholesterol declined and the width of the intima of the
common carotid artery diminished from 0.78 mm to 0.69 mm (p = 0.004). In the
above artery the maximal flow rate of blood declined. The increase was, however,
not statistically significant. In 12 patients with familial hypercholesterolaemia
who suffered from ischaemic heart disease the width of the intima of the common
carotid artery and maximum flow rate did not change, however, the diameter of the
artery increased (from 6.3 to 6.6 mm, p = 0.034). In 27 patients with familial
combined hyperlipidaemia during the drop of cholesterol, LDL-cholesterol and
triacylglycerols the width of the intima of the common carotid artery diminished
(from 0.72 to 0.67 mm, p = 0.044), the diameter of the artery increased (from 6.1
to 6.4 mm, p = 0.014). The authors assume that the reduction of the width of the
intima during hypolipidaemic treatment reflected the decline of cholesterol in
the arterial wall and is a favourable sign which indicates possible regression of
atherosclerosis.
PMID- 9650503
TI - [10 years' of care of adult patients with cystic fibrosis].
AB - The authors summarized the results of ten years care of adult patients with
cystic fibrosis (CF). They treated a total of 45 patients incl. 26 men and 19
women. Nineteen patients (42%) died. The most frequent cause of admission to
hospital was respiratory infection (84%), planned antibiotic treatment (6.5%),
pneumothorax (6%) and haemoptysis (4%). In all patients impaired ventilation of
the obstructive type was found. The mean annual decline of FEV1 was 0.173 +/-
0.194 l, VC 0.303 +/- 0.323 l. The authors did not find a significant difference
between live and dead patients. The mean annual increase of PaCO2 was 0.5 +/-
0.87 kPa, the mean annual decrease of PaO2 was 0.6 +/- 0.96 kPa. The difference
of values in dead and live patients was significant. CF still remains an
incurable disease. It is, however, possible by comprehensive treatment to prolong
the patients life and to improve its quality.
PMID- 9650504
TI - [Endogenous levels of somatostatin, C-peptide and insulin in acute pancreatitis].
AB - The authors compared in seven patients with acute pancreatitis the levels of
endogenous somatostatin, insulin and C-peptide to assess their mutual correlation
and relation to the development of the disease and serum amalyse levels. The
results were compared with values recorded in 11 healthy volunteers. The levels
of endogenous somatostatin were in patients with acute pancreatitis significantly
higher (p < 0.05) than in the control group. The authors found an inverse
relationship between the somatostatin and amylase level (correlation coefficient
0.75). They did not observe a significant correlation between somatostatin and
insulin levels nor between somatostatin and C-peptide levels. The elevated
somatostatin level may be due to the counteregulatory reaction during secretion,
stimulated by endogenous or exogenous factors (cholecystokinin, alcohol, food).
PMID- 9650505
TI - [Significance of vegetative nerve tone in patients with vasovagal
neurocardiogenic syncope].
AB - The timely provided and precise diagnostic of the syncopal states as well as
their causal therapy is a main subject of many medical branches interest within
last time. Our work was concentrated on a vasovagal neurocardiogenic syncope. The
definition of the vegetative nervous tonus participation on its development by a
method of evaluation of the heart rate variability as well as the review of a
possibility to the application of quantification these results to a prediction of
vasovagal reaction, respective of its malignant variant, was the main aim of our
effort. Our results enable a conclusion, that the observation of aquiet autonomic
nervous tonus does not represent a contribution to a differential diagnostics of
syncope of uncleared etiology with a suspicion on vasovagalous neurocardiogenous
syncope, because the basal vagal tonus does not allow the forecast of head
upright tilt table testing results as well as determination of the type of
respectively provocated vasovagal neurocardiogenic syncope. However, a
correlation between an actual reactive vageous tonus surveyed by the SD index for
patients with vasovagal neurocardiogenic syncope of the type I and IIa in
comparison with healthy persons, was found out. It allows to draw a conclusion,
that the vasovagal neurocardiogenic syncope is not homogeneous nosological unit,
what results in efforts to it's more detailed classification.
PMID- 9650506
TI - [Plasminogen activator inhibitor (PAI-1) and markers of endothelial dysfunction
in patients with diabetes mellitus].
AB - The authors examined 25 patients with diabetes mellitus type 2 (NIDDM) without
vascular complications, treated by sulphonyl urea preparations, 12
hyperinsulinaemic (HI) non-diabetic subjects and 11 normoinsulinaemic healthy
subject s. Patients with NIDDM and HI non-diabetics had significantly elevated
PAI-1 levels which correlated with the C-peptide level (r = 0.519, p < 0.001),
triacylglycerols (TG) (r = 0.685, p < 0.001), BMI (r = 0.607, p < 0.001) and
levels of endothelial markers such as von Willebrand s factor and thrombomodulin
(TM). In the group of patients with NIDDM no relationship of PAI-1 and C-peptide
was found and a significant correlation was found with TM levels (r = 0.609, p =
0.001) and TG levels (r = 0.476, p = 0.046). The results suggest that the
endothelial department has an effect on the regulation of PAI-1 levels in
patients with NIDDM.
PMID- 9650507
TI - [The effect of sulodexide, a glycosaminoglycan, on albuminuria in diabetic
patients].
AB - The authors administered to type 1 diabetics (n = 15) or type 2 diabetics (n =
20) with microalbuminuria or macroalbuminuria for a period of 15 days i.m. doses
of sulodexide (Vessel Due F), 600 i.u. (i.e. 60 mg). The evaluation of the whole
group revealed a statistically significant reduction of the original mean value
of albuminuria (509 +/- 127 ug/min) already during the first week of sulodexide
administration (382 +/- 105). A further decrease was recorded after the second
and third week of treatment (326 +/- 89, 319 +/- 85 ug/min). While in diabetics
with microalbuminuria < 100 micrograms/min the mean levels of excreted albumin
were not affected, in diabetics with macroalbuminuria 200 ug/min a significant
reduction of albuminuria persisted (p < 0.001) achieved during sulodexide
treatment persisted for three weeks after completed treatment. No differences
were found between the results of type 1 and type 2 diabetics. CONCLUSION:
Seventy-seven per cent type 1 and type 2 diabetics responded to parenteral
sulodexide administration for 15 days by a statistically significant reduction of
albumin.
PMID- 9650508
TI - [Calciphylaxis in a patient on long-term dialysis].
AB - Calciphylaxis is a special form of soft tissue calcification (in particular blood
vessels), affecting specially patients with chronic renal insufficiency and
associated secondary hyperparathyroidism. Most severely affected are small
arteries with a diameter of 0.2-0.5 mm at the interface of the corium and
subcutaneous layer. Calcification of the vascular media with subsequent narrowing
of the lumen causes ischaemic changes manifested by the development of painful
reddish-violet spots on the skin with necrosis and ulcerations. The authors
describe the case of a 73-year-old diabetic female patient with regular
dialyzation treatment. The patient developed reddish-violet spots on the lower
extremities shortly before admission to hospital. At the site of the spots
rapidly progressing necroses developed. The cause of these ischaemic changes were
calciphylactic changes confirmed on post-mortem examination and by histological
examination.
PMID- 9650509
TI - [Autologous transplantation of peripheral hematopoietic cells in a patient with
multiple myeloma and renal insufficiency].
AB - High dosage melfalan chemotherapy with subsequent autologous blood stem cell
transplantation in suitably selected patients with multiple myeloma greatly
increases the probability that complete remission will be achieved and it
prolongs the mean survival period as compared with classical chemotherapy. Till
recently patients with multiple myeloma and renal insufficiency were not included
in transplantation programmes. Only recently several papers were published abroad
which indicate the possibility to implement transplantations also in these
patients. The authors describe the treatment, incl. the first autologous
transplantation of blood stem cells in a patient with multiple myeloma and renal
insufficiency.
PMID- 9650510
TI - [Stress echocardiography in "non-ischemic myocardial disease"].
AB - Stress echocardiography is nowadays an integral part of the diagnosis of
ischaemic heart disease. In the submitted review the authors draw attention to
the fact that ischaemic heart disease is no longer the domain of stress
echocardiography. In recent years the interest of cardiologists in this method
increased also in other cardiac diseases. Based on the appropriate
pathophysiological mechanism of cardiac affection stress echocardiography is used
to test left ventricular function after a dynamic or pharmacological stress, i.e.
increased cardiac activity and cardiac minute volume in a number of heart
diseases where we must know the extent of left ventricular affection and the
functional reserve of the myocardium. These tests were also introduced to
evaluate the impact of valvular disease and function of artificial grafts to
evaluate left ventricular function in the transplanted heart. Stress
echocardiograph holds its place also in paediatrics.
PMID- 9650511
TI - [Present trends in the pathogenesis, diagnosis and therapy of vasovagal syncope].
AB - Vasovagal syncope is the most frequent cause of syncopal conditions. In its
pathogenesis autonomic nervous, neurohumoral, cerebrovascular and other
mechanisms participate. The gold standard in the diagnosis of vasovagal syncope
is in recent years the head up tilt test. In treatment pharmacotherapy, cardiac
pacing or their combination can be used.
PMID- 9650513
TI - Annonaceous acetogenins as natural pesticides: potent toxicity against
insecticide-susceptible and -resistant German cockroaches (Dictyoptera:
Blattellidae).
AB - Six compounds, representing the mono-tetrahydrofuran (THF) (gigantetrocin A,
annomontacin), adjacent bis-THF (asimicin, parviflorin), and nonadjacent bis-THF
(sylvaticin, bullatalicin) classes of annonaceous acetogenins, were compared with
technical grades of synthetic amidinohydrazone (hydramethylnon), carbamate
(propoxur, bendiocarb), organophosphate (chlorpyrifos), and pyrethroid
(cypermethrin) insecticides to determine their dietary toxicities to insecticide
resistant and insecticide-susceptible strains of the German cockroach, Blattella
germanica (L.). Differential susceptibility occurred among B. germanica nymphs of
both strains to this variety of the acetogenins and the 5 conventional synthetic
insecticides. The speed of kill (LT50) values against insecticide-susceptible and
insecticide-resistant 2nd and 5th instars permitted ranking of all 11 compounds.
The adjacent bis-THF acetogenins showed the highest potency among the 3
acetogenin classes. The acetogenins caused high percentages of mortality and
delays in development of the 5th instars of both strains. Insecticide-susceptible
nymphal development was mainly affected by gigantetrocin A and annomontacin,
whereas insecticide-resistant nymphal development was mainly affected by
gigantetrocin A and bullatalicin. Most tested acetogenins performed better than
the conventional insecticides against both stages of both strains. No growth
regulation effects were caused by any of the compounds tested. Low resistance
ratios were obtained for most compounds (except chlorpyrifos). Low resistance
ratios values for 2nd instars ranged from 0.9 to 2.2 with the natural acetogenins
and from 1.0 to 3.8 with the synthetic compounds; the 5th instars ranged from 0.2
to 3.9 with the natural acetogenins and from 0.6 to 8.0 with the synthetic
compounds. Insecticidal properties and characteristics of acetogenins and the
possible use of acetogenins in baits for cockroach control are discussed.
PMID- 9650514
TI - Delivery of ivermectin by injectable microspheres.
AB - A bioabsorbable, injectable microsphere formulation containing ivermectin in poly
(lactide-co-glycolide) copolymer (PLA/PGA) was developed to provide long-lasting
delivery of the drug for control of livestock pests. A solvent-evaporation
technique was used to produce the spherical beads containing approximately 30%
ivermectin and ranging in size from 25-250 microns. The pattern of delivery of
the drug into the blood stream of Spanish goats was characterized for a 50:50
PLA/PGA, a 90:10 PLA/PGA copolymer formulation, and a PLA monomer formulation.
When the 50:50 PLA/PGA formulation was used in cattle at the rate of 2 mg (AI)/kg
body weight, 2 peaks of 45-50 ppb of ivermectin in serum were observed. The 1st
peak was at approximately 1 wk after injection and the 2nd peak, which was
broader than the 1st, occurred at approximately 6-7 wk after injection.
Percentage of inhibition of estimated larvae for the lone star tick, Amblyomma
americanum (L.), placed on treated cattle was 100% for the first 8 wk after
injection and was 75, 57, 46 and 44% for wk 9, 10, 11, and 12, respectively. The
treatment provided 98-100% control of larval horn flies, Haematobia irritans
(L.), in the manure of treated cattle for 10 wk. The bioassay results against
lone star ticks and larval horn flies were in agreement with the serum
concentration data. The injectable microsphere formulation of ivermectin should
be useful in a variety of other applications ranging from the control of
Boophilus spp. ticks in south Texas to heartworms in pets.
PMID- 9650515
TI - Typhaea stercorea (Coleoptera: Mycetophagidae), a carrier of Salmonella enterica
serovar Infantis in a Danish broiler house.
AB - In December 1994, Salmonella enterica serovar Infantis (S. Infantis) was
accidentally introduced into a Danish broiler house by stocking an S. Infantis
infected broiler flock of 39,900 day-old chicks. At the time of the study, the
infection had persisted through 6 broiler cycles. Typhaea stercorea (L.), the
hairy fungus beetle, was found in large quantities inside and around the broiler
house. Various attempts to control the beetle had failed; T. stercorea had been
uncontrollable on the farm since Alphitobius diaperinus (Panzer), the lesser
mealworm, was eradicated approximately 10 yr earlier. We investigated the ability
of T. stercorea to act as a carrier of S. Infantis in the broiler house between 2
broiler cycles. We examined the empty, cleaned, and disinfected broiler house for
S. Infantis 3 d before stocking the 7th broiler flock, and S. Infantis was
isolated from the beetles only. Of 20 singly examined T. stercorea, 9 (45%) were
S. Infantis positive. A rapid spread of the infection was seen in the 7th broiler
flock; 100% of the culled chicks were S. Infantis positive 3 d after stocking.
Under experimental conditions chicks were observed eating beetles, and when 5 d
old, specified pathogen-free chicks were fed with S. Infantis-positive T.
stercorea collected from the broiler house, all 5 chicks became infected in 4 d.
We conclude that T. stercorea may act as a potential carrier of S. Infantis
between successive broiler cycles.
PMID- 9650518
TI - Migraine. More than a headache.
PMID- 9650517
TI - Prevention. Who should take cholesterol-lowering drugs?
PMID- 9650519
TI - Recommendations updated for hypertension.
PMID- 9650520
TI - My teeth look yellow and I've considered bleaching them. Can I do this at home or
do I need to go to the dentist?
PMID- 9650522
TI - Irradiation may make meat supply safer.
PMID- 9650521
TI - Gaining weight increases breast cancer risk.
PMID- 9650523
TI - Clear thinking on tamoxifen.
PMID- 9650524
TI - Taking the sting out of shingles.
PMID- 9650525
TI - Cataracts: when is surgery necessary?
PMID- 9650526
TI - Taking advantage of gallstone advances.
PMID- 9650527
TI - Do cholesterol-lowering drugs reduce stroke risk?
PMID- 9650528
TI - Who needs to take antibiotics before dental work?
PMID- 9650529
TI - Is it normal for hives to last longer than a month?
PMID- 9650530
TI - Cloning of intestinal phospholipase A2 from intestinal epithelial RNA by
differential display PCR.
AB - Differential display polymerase chain reaction (DD-PCR) is a powerful technique
for comparing gene expression between cell types, or between stages of
development or differentiation. Differentially expressed genes may be cloned and
analysed further. Here we extend the use of DD-PCR to analyse differences in gene
expression between two complex epithelia: that of the small intestine and of the
large intestine. The aim of this study was to identify genes expressed
preferentially in Paneth cells. Paneth cells are secretory epithelial cells
putatively involved in host defense and regulation of crypt cell proliferation
and are found at the base of the small intestinal crypts adjacent to the stem
cell zone. Of 34 clones that were analysed, partial sequencing identified two
clones related to known Paneth cell products: a homologue of secretory
phospholipase A2 (clone B1) and a homologue of a neutrophil defensin (clone C5).
B1 was strongly expressed in Paneth cells, as demonstrated by in-situ
hybridization. B1 was also expressed at a lower level in the large intestinal
epithelium. A full length B1 cDNA clone was isolated and sequenced, and shown to
be highly homologous to type II secretory phospholipase A2 genes, and almost
identical to the enhancing factor gene and the putative gene for the MOM-1 locus.
B1 expression is limited to the intestinal tract, and we propose that it be
designated intestinal phospholipase A2, or i-PLA2. The method we describe is well
suited to the rapid identification of genes expressed exclusively or
predominantly in Paneth cells.
PMID- 9650531
TI - Unbalanced growth in mouse cells with amplified dhfr genes.
AB - When grown in the absence of methotrexate, cells carrying unstably amplified
dihydrofolate reductase (dhfr) genes have a growth disadvantage that is a
function of their level of gene amplification. Although this growth disadvantage
is thought to drive the loss of unstably amplified dhfr genes in the absence of
methotrexate, its mechanism is not understood. The present studies of murine cell
lines with different levels of dhfr gene amplification demonstrate that such
cells experience increased unbalanced growth (excess RNA and protein content
relative to DNA content) with increased levels of dhfr gene amplification.
Stathmokinetic analysis of a cell line with unstably amplified dhfr genes showed
that the unbalanced growth was associated with a very low rate of G1/S transit,
which suggests that amplified DNA sequences may activate a cell cycle checkpoint
at the G1/S boundary. Hydroxyurea, which is known to induce rapid elimination of
amplified genes at sub-cytotoxic concentrations, also inhibits the cell cycle at
the G1/S transition and causes unbalanced growth. Earlier work has shown that
hydroxyurea selectively targets those cells within the heterogeneous drug
resistant cell populations which have the highest amplified gene dosage. The
finding that unstable gene amplification and hydroxyurea have similar effects on
the cell suggests that hydroxyurea may achieve this selective targeting by
pushing those cells with the highest levels of gene amplification over a critical
stress threshold to cause growth arrest or cell death.
PMID- 9650532
TI - Roles of epidemiology, pathology, molecular biology, and biomarkers in the
investigation of occupational lung cancer.
AB - The pathology and molecular biology of lung cancer demonstrate that these tumors
evolve through a series of mutations, molecular changes, and corresponding
morphologic changes. To elucidate how occupational and environmental factors
influence lung cancer histogenesis it is important not only to understand
epidemiology and the interactions between etiologic agents but also to integrate
information from pathology, biochemistry and molecular biology. This review
focuses on the range of techniques currently available for characterizing lung
cancer and how their prudent use can be beneficial in the identification of
occupational carcinogens. Because many occupational and environmental lung
cancers are caused by multiple etiologic agents, the integration of histology
with cellular, biochemical and molecular biomarker techniques may provide new
approaches for understanding the disease process.
PMID- 9650533
TI - The alveolar macrophage as a model of calcium signaling in oxidative stress.
AB - Regulation of the free intracellular calcium concentration, [Ca2+]i, plays a
major role in physiological signal transduction. Many of the essential enzymes in
signaling cascades are Ca(2+)-dependent, as are numerous proteins that
participate in the regulated function. Oxidative stress, which for many years was
considered synonymous with cell and tissue injury, has more recently been
demonstrated to alter signal transduction in both positive and negative
directions. The realization that hydrogen peroxide and lipid hydroperoxides are
produced as part of normal metabolism has led to the proposal that these oxidants
function as second messengers. Exposure to environmental and other agents that
produce hydroperoxides or the addition of exogenous hydroperoxides also causes
elevation of [Ca2+]i in some cells. At sublethal exposure to hydroperoxides, the
elevation in [Ca2+]i can either alter or mimic physiological stimulation. In
addition to endoplasmic reticulum, mitochondria, and the extracellular space, the
phospholipid- and Ca(2+)-binding proteins known as annexins constitute a Ca2+
pool from which this ion may be released under situations of oxidative stress. In
this article, the source and consequences of Ca2+ elevation are reviewed with an
emphasis on studies done with alveolar macrophages. These phagocytes, which
modulate much of the physiological and immunological function of the lung, are
susceptible targets for environmental oxidants.
PMID- 9650534
TI - Need for dietary control by caloric restriction in rodent toxicology and
carcinogenicity studies.
AB - The conditions under which laboratory animals are maintained can powerfully
influence the results of toxicological studies utilized for risk assessment.
Nutrition is of importance in toxicological bioassays and research, because diet
composition and the conditions under which it is fed can affect the metabolism
and activity of xenobiotic test substances and alter the results and
reproducibility of long-term studies. It is known that ad libitum (AL) overfed
sedentary laboratory rodents suffer from an early onset of degenerative disease
and diet-related tumors that lead to poor survival in chronic bioassays. AL-fed
animals are not well-controlled subjects for any experimental studies.
Examination of study-to-study variability in food consumption, body weight, and
survival in carcinogenicity studies for the same strain or stock of rodents shows
tremendous laboratory-to-laboratory variability. However, a significant
correlation between average food (calorie) consumption, adult body weight, and
survival has been clearly established. The use of moderate dietary restriction
(DR) results in a better controlled rodent model with a lower incidence or
delayed onset of spontaneous diseases and tumors. Operationally simple, moderate
DR significantly improves survival, controls adult body weight and obesity,
reduces age-related renal, endocrine, and cardiac diseases, increases exposure
time, and increases the statistical sensitivity of these expensive, chronic
bioassays to detect a true treatment effect. A moderate DR regimen of 70-75% of
the maximum unrestricted AL food intake is recommended as a nutritionally
intelligent, well-established method in conducting well-controlled toxicology and
carcinogenicity studies.
PMID- 9650535
TI - Chemical and epidemiological aspects of modified butter oil fractions.
AB - Butter lipids are an important traditional source of dietary energy intake in the
form of fat. Butter lost a sizable portion of its market share due to
controversies associated with its cholesterol content and high percentage of long
chain saturated fatty acids. Accordingly, the use of vegetable oils and their
chemically manipulated counterparts such as those produced by partial
hydrogenation or interestrification increased proportionally. However, beginning
in 1940, researchers developed several procedures such as temperature-controlled
crystallization, refractionation of crystallized butter oil solids, and
supercritical carbon dioxide extraction to improve the acceptance of butter oil.
Others proposed preparation of synthetic substitutes such as sucrose polyesters
to reduce intestinal absorption of fatty acids, thus reducing caloric intake with
concomitant reduction in serum cholesterol. The present review provides a summary
of the efforts of several attempts to improve the acceptability of butter
together with the anticipated epidemiological consequences of long-term
consumption of altered butter oil to mammalian health.
PMID- 9650536
TI - Use of angiotensin-converting enzyme inhibitors as monotherapy and in combination
with diuretics and calcium channel blockers.
AB - Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in
medical therapy since their discovery about two decades ago. This family of drug
has grown tremendously since the introduction of captopril in 1981. There are
currently more than 14 ACE inhibitors in the world and 9 are available in the
United States. Although these agents share many similarities, they differ in
their pharmacokinetic properties, approved indications, and cost. This paper
provides guidance for selection of ACE inhibitors by examining the
pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, and cost
of these agents. Combination products of ACE inhibitors with either diuretics or
calcium channel blockers also are reviewed.
PMID- 9650537
TI - Effect of multiple doses of rifampin on the [14C N-methyl] erythromycin breath
test in healthy male volunteers.
AB - The erythromycin breath test (EBT), which measures 14CO2 produced from [14C N
methyl] erythromycin, is one of the most frequently employed measures to examine
drug interactions involving cytochrome P450 3A4 (CYP3A). However, the
reproducibility and reliability of this test, and the effects of drugs that alter
CYP3A activity, continue to be defined. In this study, the reproducibility of the
EBT was evaluated in eight healthy volunteers before and after oral
administration of 600 mg of rifampin daily for 8 days. Two sequential EBT
determinations performed 5 days apart before rifampin administration were highly
reproducible. Rifampin induced CYP3A, reflected in a mean percent (+/- standard
deviation) increase in EBT values of 86 +/- 30%. Recovery of enzyme function
after discontinuation of rifampin for 17 days was manifested as a return of EBT
values to preinduction levels. These results support the utility of EBT as a
valid, reproducible, and reliable measure of CYP3A activity in vivo.
PMID- 9650538
TI - Intravenous and oral propafenone for treatment of tachycardia in infants and
children: pharmacokinetics and clinical response.
AB - To elucidate contribution of an active metabolite to overall clinical responses
to propafenone, steady-state disposition of propafenone and its active metabolite
and the clinical responses to treatment were examined in pediatric patients
receiving intravenous or oral propafenone. There were more than ten-fold
interindividual differences in apparent clearance, resulting in a wide range of
the steady-state trough plasma concentrations of propafenone. The active
metabolite, 5-hydroxypropafenone, was detected in four of the six patients
receiving oral propafenone; however, two neonates receiving oral propafenone and
all eight receiving intravenous propafenone had no detectable levels of 5
hydroxypropafenone in plasma. In nine patients for whom electrocardiographic
(ECG) data were available, the PQ interval was significantly increased, whereas
the QRS duration and the QTc interval were not. There was no close relationship
between plasma concentrations of propafenone or 5-hydroxypropafenone and ECG
parameters. Lack of good correlation between serum concentrations and clinical
response precludes using a serum-concentration targeting strategy with
propafenone therapy.
PMID- 9650539
TI - Application of serum nicotine and plasma cotinine concentrations to assessment of
nicotine replacement in light, moderate, and heavy smokers undergoing transdermal
therapy.
AB - As part of a clinical trial investigating the level of nicotine replacement with
different doses of transdermal therapy for smoking cessation, peak and trough
serum nicotine and plasma cotinine concentrations were measured in 70 subjects
while they were actively smoking (baseline) and daily for 6 consecutive inpatient
days while they were receiving transdermal nicotine. Subjects were randomly
assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0,
11, 22, or 44 mg and stratified by self-reported smoking rate as either light (10
15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30
cigarettes per day). Steady-state concentrations of nicotine and cotinine were
attained in 1 and 3 days, respectively, at all doses and were independent of
baseline smoking rate. Mean percentage replacement of nicotine was calculated by
dividing steady-state peak nicotine or cotinine concentrations by their
respective baseline concentrations. Significant underreplacement occurred in
subjects receiving the 11 mg/day patch regardless of baseline smoking rate.
Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day
and in light smokers at this same dose. Complete replacement occurred only in
subjects receiving the 44 mg/day patch. These results have several implications
for transdermal nicotine therapy. First, with the higher nicotine and cotinine
levels observed with heavier smoking, it is inherent that one size does not fit
all, and there is a need to consider more individualization of dosage for
nicotine patch therapy. Second, there is substantial underreplacement with the 22
mg/day dose in moderate to heavy smokers and in some light smokers. Third, even
with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either
nicotine or cotinine. Plasma cotinine levels after achievement of steady state
(i.e., after 3 days of patch therapy) can be collected at any time and used to
calculate percent replacement using baseline levels.
PMID- 9650540
TI - Application of urine nicotine and cotinine excretion rates to assessment of
nicotine replacement in light, moderate, and heavy smokers undergoing transdermal
therapy.
AB - As part of a clinical trial investigating the level of nicotine replacement with
different doses of transdermal therapy for smoking cessation, urine excretion
rates of nicotine and cotinine were measured in 70 subjects while they were
actively smoking (baseline) and for 6 consecutive inpatient days while they were
receiving transdermal nicotine therapy. Subjects were stratified according to
baseline smoking rate as light (10-15 cigarettes per day), moderate (16-30
cigarettes per day), or heavy (>30 cigarettes per day) smokers and randomly
assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0,
11, 22, or 44 mg. Steady-state excretion rates of nicotine and cotinine were
attained in 2 and 3 days, respectively, at all doses and were independent of
smoking rate. Percentage replacement of nicotine was calculated by dividing
steady-state nicotine or cotinine excretion rates by their respective baseline
excretion rates. Significant underreplacement occurred with the 11-mg/day dose,
particularly in moderate and heavy smokers (<50%). At a dose of 22 mg/day,
nicotine replacement was still <100% in the majority of subjects. Only at a dose
of 44 mg/day did mean replacement exceed 100% regardless of baseline smoking
rate.
PMID- 9650541
TI - Pharmacokinetics of rifapentine in patients with varying degrees of hepatic
dysfunction.
AB - In this open-label investigation, the pharmacokinetics of rifapentine and its
active metabolite, 25-desacetyl-rifapentine, were characterized in patients with
varying degrees of hepatic dysfunction. Eight patients with mild-to-moderate
chronic, stable hepatic dysfunction and seven patients with moderate-to-severe
hepatic dysfunction received single oral 600-mg doses of rifapentine. Maximum
plasma concentration of rifapentine was lower, time to maximum plasma
concentration (tmax) was greater, and elimination half-life (t 1/2) was longer in
the patients with moderate-to-severe hepatic dysfunction than in those with mild
to-moderate dysfunction. However, mean area under the concentration-time curve
extrapolated to infinity (AUC0-infinity) for the two groups was similar. AUC0
infinity values in patients with hepatic dysfunction were 19% to 25% higher than
values previously reported for healthy volunteers. The 25-desacetyl metabolite
appeared in plasma slowly after the single oral dose of rifapentine. Similar to
findings for the parent drug, comparable plasma exposures of 25-desacetyl
rifapentine based on AUC0-infinity were found in the two groups of patients with
mild-to-moderate and moderate-to-severe hepatic dysfunction. Rifapentine was well
tolerated in this patient population, irrespective of the etiology or severity of
hepatic dysfunction. These safety and pharmacokinetic results suggest that no
dosage adjustments for rifapentine are needed in patients with hepatic
impairment.
PMID- 9650542
TI - Pharmacokinetics of intravenous and oral losartan in patients with heart failure.
AB - The pharmacokinetics of a selective AT1-subtype, nonpeptide, orally active,
angiotensin II receptor antagonist, losartan, were characterized in 11 patients
with heart failure (New York Heart Association class II, n = 6; class III, n = 4;
class IV, n = 1) after oral and intravenous administration. In these patients,
average plasma clearance of losartan was 566 mL/min, volume of distribution at
steady-state was 34 L, and terminal plasma half-life was 1.5 hours. Average
bioavailability was 36%. No clinically significant accumulation of losartan or
its active metabolite, EXP3174, occurred after multiple-dose oral administration
for 7 to 8 days. Terminal plasma half-life of EXP3174 after oral administration
of losartan was 7.6 hours. The pharmacokinetics of losartan in patients in this
study appear to be similar to those in healthy subjects studied previously.
PMID- 9650543
TI - Pharmacokinetics of acetazolamide in healthy volunteers after short- and long
term exposure to high altitude.
AB - Exposure to high altitude results in significant physiologic changes and may
precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe
symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of
meperidine were observed after exposure to high altitude. This study was
conducted to investigate whether similar changes occur for acetazolamide, which
is prescribed for prophylaxis of acute mountain sickness. Acetazolamide 250 mg
was administered orally to young, healthy male volunteers in groups of 12 each:
those residing at sea level (group L), these same volunteers on the day after
arrival at high altitude (4,360 m, group HA), and volunteers living at high
altitude for 10 months or longer (group HC). Serial blood samples were collected
for 24 hours and acetazolamide concentrations were measured in whole blood,
plasma, and plasma water. The elimination rate constant (lambda z) was
significantly increased in group HA compared with group L. Clearance uncorrected
for bioavailability (Cl/F) increased significantly in group HA compared with
group L, and further increased in group HC. Apparent volume of distribution
(Vz/F) was decreased by 17% in group HA compared with group L, and increased by
37% in group HC compared with group HA. Mean residence time (MRT) was
significantly decreased in group HA compared with groups L and HC. Erythrocyte
(RBC) uptake increased significantly after a significant increase in RBC count in
group HC compared with group L. The extent of protein binding (EPB), however, was
significantly decreased in group HA compared with groups L and HC. Free
acetazolamide concentrations were significantly lower in group HC than in group L
12 hours after administration. Based on these observations, it is suggested that
patients travelling to high altitude, especially altitudes above 4,000 m, should
be closely monitored and acetazolamide dosage adjusted as necessary.
PMID- 9650544
TI - A novel recombinant soluble human thrombomodulin, ART-123, activates the protein
C pathway in healthy male volunteers.
AB - The effect of a novel recombinant soluble human thrombomodulin, ART-123, on
protein C activation was investigated by measuring plasma prothrombinase activity
in four healthy male volunteers. ART-123 at a dose of 0.3 mg was administered as
a bolus intravenous injection for 1 minute. Plasma ART-123 concentration and
prothrombinase activity were determined before and immediately, 24, and 48 hours
after injection, and thromboelastography was recorded before and immediately and
24 hours after injection. The mean elimination half-life was 19.82 +/- 2.10
hours. Compared with pretreatment levels, ART-123 reduced prothrombinase activity
by 44.2 +/- 11.7%, 52.1 +/- 10.8%, and 61.0 +/- 14.7%, respectively, immediately,
24, and 48 hours after injection, suggesting that ART-123 activated the protein C
pathway. ART-123 did not affect thromboelastography values. There were no
abnormal findings for objective signs or laboratory tests, including blood
pressure, heart rate, electrocardiogram, body temperature, hematology,
coagulation and hemostatic parameters, blood chemistry, and urinalysis. Based on
these observations, ART-123 at a dose of 0.3 mg can activate the protein C
pathway in healthy volunteers.
PMID- 9650545
TI - Effects of oral and intravenous terazosin and head-up tilt on blood pressure
responses in patients with hypertension.
AB - Terazosin is a selective alpha1-adrenoceptor antagonist. A double-blind,
randomized, placebo-controlled, two-period study evaluated the effects of posture
and of oral and intravenous administration of terazosin on blood pressure and
heart rate in patients with hypertension. At least one week after withdrawal of
all antihypertensive medications, 31 patients with sitting diastolic blood
pressure of 95 to 114 mmHg were enrolled in the study. After a 24-hour, single
blind, placebo lead-in phase, the patients were randomized to receive either oral
terazosin (1 mg on day 1, 2 mg on day 2, and 5 mg on days 3 and 4), a 12-hour
intravenous infusion of terazosin (2.5 mg, 5 mg, or 7.5 mg), or placebo for 4
consecutive days. Head-up tilt (60 degrees for 20 minutes) evaluations were
performed before and 0.5, 1.5, 2.5, 6, 12, and 16 hours after start of
administration during the placebo lead-in phase and on each of the 4 days of the
double-blind treatment phase. Blood pressure and heart rate were monitored every
2 minutes during the 20-minute tilt. Statistically significantly larger mean
changes in blood pressure and heart rate were observed with the 7.5-mg
intravenous dose of terazosin compared with those after oral terazosin or
placebo. With respect to intravenous terazosin, the orthostatic changes were
maximal on the first day of the 4-day treatment and increased with increasing
doses of terazosin. Maximum orthostatic changes in blood pressure after oral
administration of terazosin were not significantly different from those observed
with placebo. The most common treatment-emergent adverse events during tilt were
dizziness and nausea. Dizziness occurred more frequently with intravenous
terazosin than with oral terazosin. The results of this study indicate that oral
dose titration of terazosin rather than a slower rate of terazosin infusion
minimized the postural effects on blood pressure and associated symptoms during
head-up tilt.
PMID- 9650546
TI - Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with
codeine, and placebo after dental extraction.
AB - Tramadol hydrochloride is a novel, centrally acting analgesic with two
complementary mechanisms of action: opioid and aminergic. Relative to codeine,
tramadol has similar analgesic properties but may have fewer constipating,
euphoric, and respiratory depressant effects. A two-center randomized double
blind controlled clinical trial was performed to assess the analgesic efficacy
and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg,
aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar
extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation
after a single dose of drug. Of the 200 patients enrolled, seven provided
incomplete efficacy data or discontinued prematurely and one was lost to follow
up. Using standard measures of analgesia, including total pain relief score
(TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference
scores (SPID), peak pain intensity difference (Peak PID), remedication, and
global evaluations, all active treatments were found to be numerically superior
to placebo. ASA/codeine was found to be statistically superior to placebo for all
measures of efficacy. Tramadol 100 mg was statistically superior to placebo for
TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically
superior to placebo onlyfor remedication time. Codeine was not found to be
statistically superior to placebo for any efficacy measure. A greater TOTPAR
response compared with all other active measures was seen for ASA/codeine during
the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and
ASA/ codeine group were not significantly different. Gastrointestinal side
effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol
100 mg, ASA/ codeine, and codeine 60 mg than with placebo.
PMID- 9650547
TI - Pentoxifylline potentiates in vitro lymphocyte suppression by glucocorticoids and
immunosuppressive drugs.
AB - Pentoxifylline, which has immunomodulatory effects in addition to its better
known rheologic effects, might potentiate the effectiveness of traditional
immunosuppressive drugs. We therefore studied the suppressive effect of
pentoxifylline in combination with clinically relevant concentrations of
prednisolone, methylprednisolone, cyclosporine, tacrolimus, rapamycin, and
mycophenolic acid on mitogen-stimulated lymphocytes from 29 patients with
glomerular diseases. Inhibition of lymphocyte proliferation obtained with 10(-7)
and 10(-8) mol/L concentrations of the glucocorticoids and with 300 ng/mL
cyclosporine was significantly increased when each was combined with 5, 25, or 50
microg/mL of pentoxifylline. The additive inhibitory effect of pentoxifylline in
combination with 10(-7) mol/L glucocorticoids was inversely proportional to the
inhibitory effect of the 10(-7) mol/L concentration of glucocorticoid alone,
suggesting that the less sensitive the patient's cells, the greater the
potentiation by pentoxifylline. The greatest degree of potentiation by
pentoxifylline occurred when combined with the lower (10(-8) mol/L) concentration
of glucocorticoids. Pentoxifylline also significantly increased lymphocyte
suppression in combination with 150 and 300 ng/mL concentrations of cyclosporine,
5 ng/mL of tacrolimus, 2.5 x 10(-7) mol/L mycophenolic acid, and 10 ng/mL of
rapamycin. These in vitro results suggest that pentoxifylline might have steroid
sparing effects and contribute to improved clinical outcomes from
immunosuppressive treatment of renal diseases.
PMID- 9650548
TI - High resolution deletion mapping reveals frequent allelic losses at the DNA
mismatch repair loci hMLH1 and hMSH3 in non-small cell lung cancer.
AB - To study the involvement of DNA mismatch repair genes in non-small cell lung
cancer, matched normal and tumoral DNA samples from 31 patients were analyzed for
both LOH and microsatellite instability with 34 markers at or linked to hMLH1
(3p21), hMSH2 (2p16), hMSH3 (5q11-q13), hMSH6 (2p16), hPMS1 (2q32), and hPMS2
(7p22) loci. Chromosomal regions 3p21 and 5q11-q13 were found to be hemizygously
deleted in 55% and 42% of the patients, respectively. Sixty five percent of the
patients deleted at hMLH1 were also deleted at hMSH3. The shortest regions of
overlap for 3p21 and 5q11-q13 deletions delimited by D3S1561/D3S1612 and
D5S2107/D5S624, respectively, were restricted to genetic distances of only 1 cM.
Currently, the hMLH1 (3p21) and hMSH3 (5q11-q13) genes are the only known
candidates located within these regions. The mutational analysis of hMLH1 and
hMSH3 in hemizygously deleted patients led to the detection of 2 new
polymorphisms in hMSH3. The consequence of these allelic losses remains unclear,
but the lack of inactivating mutation might explain that replication error, the
hallmark of mismatch repair genes inactivation in cancer cells, was quasi-absent
in tumors. We suggest that hMLH1 and hMSH3 genes could be involved in lung
tumorigenesis through dosage effect in cellular functions other than replication
error correction.
PMID- 9650549
TI - Chimeric scFv/gamma receptor-mediated T-cell lysis of tumor cells is coregulated
by adhesion and accessory molecules.
AB - Adhesion and accessory molecules play a critical role in T-cell activation and
effector function in general and in tumor cell recognition and lysis in
particular. We investigated the contribution of CD2, CD3, CD11a/CD18, CD54 and
CD58 molecules in T lymphocyte-tumor cell interactions mediated by chimeric
immunoglobulin receptors. The chimeric receptor is composed of a single chain
antibody binding site and a gamma-chain signal transducing molecule (scFv/gamma).
T lymphocytes expressing such scFv/gamma receptors recognize the G250 Ag on renal
cell carcinoma (RCC) in an major histocompatibility complex (MHC)-unrestricted
manner and exert RCC selective cytolysis. A coregulatory role for CD2, CD3 and
CD11a/CD18 molecules in scFv/gamma-mediated cytolysis was demonstrated using
monoclonal antibody (MAb)-induced inhibition of scFv/gamma-mediated cytolysis.
The inhibition of lysis was not due to inhibition of cytotoxic T lymphocyte (CTL)
target cell conjugation but rather to a post-conjugate signaling event. Binding
of CD54 and CD58 MAbs to the RCC did not inhibit cytolysis of RCC cells that
expressed high levels of both CD54 and the G250 antigen (Ag) (A75), whereas
cytolysis of RCC expressing intermediate levels of CD54 and G250 Ag (SK-RC-17
cl.4) was partly inhibited by the CD54 MAb. Binding of low concentrations of G250
MAb to RCC (A75) rendered these cells sensitive to CD54 MAb inhibition,
demonstrating a direct functional relation between G250 Ag expression level and
adhesion molecules. Taken together, our findings indicate a coregulatory role for
CD2, CD3 and CD11a/CD18 molecules in the scFv/gamma-mediated cytolysis of tumor
cells and show that the requirement of CD11a/CD18-CD54 interactions is dependent
on the level of free Ag. This make these gene-transduced T lymphocytes attractive
tools for adoptive immunogene therapy of cancer.
PMID- 9650550
TI - Predictors of level of circulating abnormal lymphocytes among human T
lymphotropic virus type I carriers in Japan.
AB - Human T-lymphotropic virus type I (HTLV-I) carriers often have abnormal
lymphocytes (Ably) that resemble malignant cells of adult T-cell leukemia (ATL).
To identify predictors of the level of Ably in a longitudinal study of
asymptomatic HTLV-I carriers, we analyzed data from 215 subjects (67 men and 148
women) with multiple Ably measurements on blood smears. Ably+ (those having Ably
> 0.6% of leukocytes counted on a blood smear at least once) was strongly
associated with a high proviral load (OR 8.9; 95% CI 4.1, 19.5). The association
among those defined as Ably++ (Ably > 0.6% at all screens or Ably > 1.6% at least
once) was higher (19.7; 6.9, 56.1). Ably++ was also significantly associated with
male gender (2.8; 1.0, 7.8). Multivariate analysis of Ably level indicates that
men with a high proviral load, high anti-HTLV-I titer and low anti-Tax reactivity
have the highest Ably level.
PMID- 9650551
TI - MUC6 expression in breast tissues and cultured cells: abnormal expression in
tumors and regulation by steroid hormones.
AB - Neoplastic transformation of epithelial cells is commonly associated with
alterations in the expression of mucin genes. The mechanisms involved in this
process are largely unknown. MUC6, isolated from a stomach cDNA library, is
mainly expressed in stomach antral glands, as detected by using in situ
hybridization and immunohistochemistry. We examined MUC6 expression in normal and
pathological breast tissues using immunohistochemistry with MUC6-specific
antibodies and in cultured breast cancer cells using immunocytochemistry and
Northern blotting. MUC6 was generally not detected in normal breast (1/11) but
was detected in fibrocystic disease without atypia (7/17, 41%), in atypical
fibrocystic disease (11/11, 100%) and in carcinoma (57/60, 95%). To study the
mechanisms involved in mucin gene up-regulation in breast cancer, we examined
baseline, growth-related and steroid-induced levels of MUC1, MUC3 and MUC6 in 4
breast cancer cell lines, 2 of which express estrogen receptors. MUC6 levels were
up-regulated at post-confluence in 2/4 cell lines, whereas no changes were
detected for the other mucin genes examined. MUC6 and MUC3 were constitutively
expressed, and steroid-induced, in BT-474 and MCF-7 cells, respectively. As a
control, pS2 was induced in both cell lines. Our results indicate that (1) MUC6
is overexpressed in breast cancer and in benign breast disease, (2) in vitro,
MUC6 and MUC3 are up-regulated by steroids and (3) abnormal expression of MUC6 in
breast cancers may, in part, be explained by hormonal changes associated with
tumor development.
PMID- 9650552
TI - High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene
expression in clusters of multiple simultaneous metastases of human melanoma:
implications for protocol design of therapeutic antigen-specific vaccination
strategies.
AB - Human melanoma cells express several antigens which are recognized by autologous
and specific CTL clones in association with HLA-class-I molecules. Many of these
antigens represent suitable targets for tumor immunotherapy, since their
expression in human melanoma cells is common and highly specific. In order to
achieve real clinical success with therapeutic vaccination strategies, one
important requirement is the expression of the target antigen by all the tumor
lesions of a patient. We have studied this issue by assessing, through an RT-PCR
approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase
and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional
lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM
system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic
lesions (82%), the homogeneity in the pattern of gene expression within the
cluster was complete. Heterogeneity within the same cluster was observed in only
3 out of 17 clusters (18%) and represented only minor features. Our data reveal
that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic
lesions express the same pattern of antigen-coding genes. These observations have
2 main clinical implications: (i) the antigenic characterization of one single
and easily accessible lesion allows identification of optimal targets for an
active antigen-specific immunotherapy treatment; (ii) almost all the metastatic
lesions are expected to be hit by the immune response eventually induced against
the tumor antigen. Moreover, these data suggest that active specific
immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and
Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in
high-risk AJCC-stage-III-melanoma patients.
PMID- 9650553
TI - Different distribution of H1-H2 Epstein-Barr virus variant in oropharyngeal virus
and in biopsies of Hodgkin's disease and in nasopharyngeal carcinoma from
Algeria.
AB - In a previous study of Epstein-Barr virus (EBV) strains in North African
nasopharyngeal carcinoma (N PC) biopsies, we have found that the viral strain
present was of A/F/W'-I'/Xhol kept/H1-H2 type, while the strain associated with
Chinese NPC was the A/"f"/W'I'/Xhol lost/H type. Using the restriction fragment
length polymorphism (RFLP) and PCR-RFLP methods, the present study analyzed the
H1-H2 variant in different clinical samples from Algeria, including the saliva of
healthy EBV-positive individuals and patients with NPC or Hodgkin's disease (HD),
as well as HD biopsies and lymphoblastoid cell lines (LCLs) established from the
oropharyngeal virus-infected cells. Our results demonstrate that, in contrast to
the H1-H2 variant found in NPC biopsies, the H genotype was dominant in HD
biopsies. Moreover, H genotype was also dominant in the oropharynx of healthy EBV
positive individuals, of patients with NPC and with HD. Our results clearly
indicate that in North Africa the EBV strain present of NPC biopsies is different
from that shed in the oropharynx. This may suggest a specific distribution of the
H1-H2 variant in the NPC epithelial tumor, whereas the H genotype is dominant in
HD biopsies and in the oropharynx. The specific association of both viral strains
with these 2 distinct diseases in North Africa may reflect a difference in
tumorigenicity.
PMID- 9650554
TI - Cruciferous vegetables in relation to renal cell carcinoma.
AB - Little is known about the possible role of diet in the development of renal cell
carcinoma (RCC). A population-based case-control study was conducted in non
Asians of Los Angeles; it included 1,204 RCC patients and an equal number of
neighborhood controls matched to the index cases by sex, date of birth (within 5
years) and ethnicity. Information on intake frequencies of food groups rich in
vitamins A and C, various carotenoids and nitrosamines or their precursors was
collected through in-person, structured interviews. After adjustment for non
dietary risk factors including level of education, obesity, history of
hypertension, cigarette smoking and regular use of analgesics and amphetamines,
there were strong inverse associations between cruciferous and dark green
vegetable intakes and RCC risk (both p values for linear trend < 0.001). In terms
of nutrients, there were significant inverse associations of RCC risk with
consumption of a variety of carotenoids including alpha-carotene (p < 0.001),
beta-carotene (p = 0.004), beta-cryptoxanthin (p = 0.01) and lutein (p = 0.005).
However, after adjustment for these nutrients, we still observed a significant
residual effect of cruciferous vegetables, suggesting that other substances
present in these vegetables may be responsible, at least partially, for the
observed reduction in risk of RCC. Dietary nitrosamines and their precursors were
not related to RCC risk.
PMID- 9650555
TI - Cytogenetics of a malignant ovarian germ-cell tumor.
AB - Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ
cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor,
revealed a highly abnormal chromosomal pattern. We found a chromosome number in
the hypertriploid/hypotetraploid range, and several clonal structural
abnormalities, including 2 copies of an isochromosome 12p. We showed that the
chromosomal pattern of this ovarian tumor is very similar to that of testicular
germ-cell tumors. This finding, together with reported cytogenetic data of
malignant ovarian germ-cell tumors, supports the hypothesis that ovarian and
testicular germ-cell tumors are strongly related entities that may have a similar
origin and pathogenetic pathway.
PMID- 9650556
TI - Oral contraceptives and breast cancer risk in Taiwan, a country of low incidence
of breast cancer and low use of oral contraceptives.
AB - One hundred and seventy four (81% of all) pathologically confirmed new incident
cases of female breast cancer identified from a medical center in Taipei from
February, 1993 to June, 1994 were selected as the case group. Four hundred and
fifty three inpatient controls who were without obstetric-gynecological, breast,
or malignant diseases were individually matched for each case by age and date of
admission. Information was obtained through direct interview and review of
medical records. Conditional logistic regression was used to estimate the effects
of each risk factor. After adjusting for education level, body mass index, age at
menarche and first full-term pregnancy, parity, menopausal status and age at
menopause, lifetime lactation, use of lactation inhibition hormones, and family
history of breast cancer, breast cancer risk significantly elevated in use of OC
before 25 years old and before 1971. In stratified analysis, significantly higher
risk were found in OC use before 25 years old and in duration of use less than
one year among post-menopausal subjects. Our results support the notion that OC
use in early life for younger women and in early calendar years increase breast
cancer risk.
PMID- 9650557
TI - Parity and the risk of pancreatic cancer: a nested case-control study.
AB - Smoking is the only generally accepted risk factor for pancreatic cancer.
Reproductive history has in recent studies been associated with pancreatic
cancer, but with contradictory results. In order to evaluate a possible
association between age at first birth and the number of births and pancreatic
cancer, we conducted a nested case-control study by linking 2 Swedish nationwide
registries: the Cancer Registry and The Fertility Registry. Among women born
between 1925 and 1970, 1,015 patients with pancreatic cancer were compared with
5,073 age-matched controls. No association between pancreatic cancer and number
of births was found. Age at first birth was inversely related with the risk of
pancreatic cancer (OR per 5 years = 0.90; 95% CI 0.83-0.97; p = 0.01), an
association mainly confined to women with a diagnosis of pancreatic cancer before
50 years of age (OR per 5 years = 0.85; 95% CI 0.73-1.00; p = 0.04). This trend
remained after adjustment for parity, but was less prominent. Young age at first
birth and high parity in Sweden are, however, associated with an increased
frequency of smoking, thus at least some of the increased risk for pancreatic
cancer in women with young age at first birth is likely to be explained by
smoking acting as a confounder.
PMID- 9650558
TI - Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary
exposures.
AB - We interviewed 282 histologically confirmed cases of nasopharyngeal carcinoma
(NPC) in Chinese residents of Selangor and the Federal Territory, Malaysia, and
an equal number of Chinese age-, sex-, and length-of-residence-matched controls
sampled from the general population. Consumption of 55 dietary items during
childhood, and 5 years pre-diagnosis of NPC, was analyzed by univariate and
multivariate methods. Four salted preserved foods (fish, leafy vegetables, egg
and root), fresh pork/beef organ meats and beer and liquor consumption exhibited
strong positive associations, and 4 vegetable/fruit combinations strong negative
associations with NPC. Factor analysis and multivariable modeling using estimated
factor scores strongly supported separate effects on NPC of vegetables/fruits,
salted preserved foods, pork/beef organ meats and beer/liquor consumption.
Multivariable modeling associated NPC most clearly with high consumption of
salted fish, salted eggs, pork/beef liver and beer and low consumption of Chinese
flowering cabbage, oranges/tangerines and shrimp. A strong residual association
of social class with NPC remained after adjustment for diet, which is consistent
with a substantial role for non-dietary environmental factors.
PMID- 9650559
TI - Complexes between urokinase-type plasminogen activator and its receptor in blood
as determined by enzyme-linked immunosorbent assay.
AB - Complexes between urokinase-type plasminogen activator (uPA) and its receptor
(uPAR) were assessed in plasma and serum from 39 breast cancer patients and from
20 healthy individuals, applying a recently developed enzyme-linked immunosorbent
assay (ELISA) for the analysis of these complexes in tumor tissue extracts. The
assay is based on a combination of rabbit polyclonal anti-uPA antibodies for
catching and a mouse anti-uPAR monoclonal antibody (MAb) for detection. The
specificity of the assessment of uPA:uPAR complexes was verified by simultaneous
analysis of the individual blood samples in corresponding non-sense ELISA
formats, in which either the anti-uPA catching antibody or the anti-uPAR
detecting antibody was substituted with an irrelevant antibody. Assessment of
native uPA:uPAR complexes was ascertained by demonstrating the absence of any de
novo formation of uPA:uPAR complexes in plasma and serum during the sample
incubation step in the ELISA, as verified by the use of a peptide antagonist for
uPAR. Plasma and serum samples contained almost identical levels of uPA:uPAR
complexes. The levels of uPA:uPAR complexes were found to be significantly lower
in serum from breast cancer patients compared to the serum of healthy donors,
while the levels of (total) uPAR in plasma from breast cancer patients were
significantly higher than in plasma from the healthy controls. In addition, the
free, uncomplexed uPAR levels, estimated by subtraction of uPA:uPAR complex
levels from (total) uPAR levels, were significantly elevated in plasma as well as
in serum from breast cancer patients compared to healthy individuals. The
uPA:uPAR complex levels were highly comparable to the uPA levels analyzed in the
same plasma and serum samples, indicating that most if not all of the uPA present
in these samples is complexed with uPAR.
PMID- 9650560
TI - Mechanism of antitumor action of PKC activator, gnidimacrin.
AB - Daphnane-type diterpene gnidimacrin isolated from the Chinese plant Stellera
chamaejasme L. is an antitumor agent that activates protein kinase C (PKC). The
mechanism of antitumor action of gnidimacrin and the possible involvement of PKC
were examined using sensitive K562 and refractory HLE cells. Gnidimacrin did bind
to K562 cells 3 times more than to HLE cells. Immunoblot analyses revealed
pronounced PKC betaII expression in gnidimacrin sensitive cell lines including
K562 cells, while refractory HLE cells strongly expressed PKC alpha, but not PKC
betaII. In a 24-hr exposure of K562 cells to gnidimacrin, G1 phase arrest and
inhibition of cdk2 kinase activity was found at growth-inhibitory concentration
(0.0005 microg/ml). Complete inhibition of cdk2 activity and maximum G1 phase
arrest were observed at 0.005 microg/ml, however, these biological effects were
reduced at 0.05 microg/ml (260 times the 50% inhibitory concentration). Cellular
PKC after a 24-hr exposure was examined by immunoblot analysis and specific
binding of [3H]phorbol-12,13-dibutyrate as a ligand of PKC. Expression and the
amount of functional PKC of K562 cells were not changed at 0.002 microg/ml, but
down-regulated to less than 1/10th of the control at 0.05 microg/ml. The
reduction of biological effects at 0.05 microg/ml is most likely due to PKC down
regulation. Our results suggest that PKC (particularly betaII) is one of the
major determinants of the ability of cells to respond to gnidimacrin and that the
antitumor action might be associated with cell-cycle regulation through
suppression of cdk2 activity.
PMID- 9650561
TI - Anti-CD3-based bispecific antibody designed for therapy of human B-cell
malignancy can induce T-cell activation by antigen-dependent and antigen
independent mechanisms.
AB - Anti-CD3 x anti-B-cell antigen bispecific monoclonal antibodies (bsAbs) can
redirect T-cell-mediated lysis toward malignant B cells. Clinical trials with CD3
based bsAbs have shown toxicity in patients which is likely related to
nonspecific T-cell activation and targeting. Our current studies were designed to
explore the mechanisms responsible for the observed in vivo toxicity by
evaluating the immunologic effects of 2 different bsAb preparations in vitro.
1D10 was used as the tumor specific arm of the bsAbs. This antibody reacts with a
variant of HLA-DR found on a majority of pre-B- and B-cell malignancies, and
normal B cells in some individuals. Anti-CD3 served as the T-cell specific arm. A
1D10 x anti-CD3 bispecific IgG (bsIgG) produced using the hybrid-hybridoma method
was compared to a 1D10 x anti-CD3 bispecific F(ab')2 [bsF(ab')2] produced using
the leucine zipper technique. In cytotoxicity assays, both bsIgG and bsF(ab')2
induced lysis by pre-activated T cells of 1D10 (+) malignant B cells. bsIgG at
high concentrations also induced lysis of 1D10 (-) tumor cells, while bsF(ab')2
did not. Proliferation of T cells induced by bsIgG and bsF(ab')2 was also
evaluated. Both forms of bsAbs induced T-cell proliferation in the presence of
antigen (+) Raji cells, while only bsIgG did so in the presence of antigen (-)
malignant B cells. bsF(ab')2 induced T-cell activation in the absence of any
tumor cells when testing was performed on samples where the 1D10 target antigen
was present on normal peripheral blood B cells. We conclude that non-specific T
cell activation from bsAbs can occur in an antigen-independent manner due to the
Fc/Fc receptor (FcR) interaction, or in an antigen-dependent manner when antigen
is expressed on normal or tumor cells. Both mechanisms may have been responsible
for the toxicity observed in prior clinical studies.
PMID- 9650562
TI - Over-expression of urokinase receptor in human epidermoid-carcinoma cell line
(HEp3) increases tumorigenicity on chorio-allantoic membrane and in severe
combined-immunodeficient mice.
AB - Using chorio-allantoic membranes (CAMs) of chick embryos and severe-combined
immunodeficient (SCID) mice, we investigated the effects of urokinase-type
plasminogen-activator receptor (u-PAR) over-expression on the process of invasion
and tumorigenicity. By the transfection of u-PAR cDNA, 3 u-PAR-over-expressing
clones expressing 1.6- to 4.6-fold more u-PAR mRNA than parent cells were
obtained from a human epidermoid-carcinoma cell line, HEp3, that expresses
urokinase-type plasminogen activator (u-PA) and u-PAR. All the u-PAR-over
expressing clones showed greater invasiveness (13 to 29%) than that of parent
HEp3 cells on CAMs. Immunohistochemistry revealed densely stained u-PAR-positive
cells near the margin of the tumor, where a u-PAR-over-expressing clone,
designated SM-3, was invading thickened fibrous tissue on CAMs. Three u-PAR
overexpressing clones formed larger tumors (>40 mm3) than did parent HEp3 cells
on CAMs. Moreover, when the u-PAR-overexpressing clone (SM-3) was injected s.c.
into the back of the SCID mice it produced a larger tumor volume than the control
(HEp3) and down-regulated (AS-2) clones and significantly shortened the survival
of SCID mice. These results demonstrate that increased u-PAR expression is an
important factor in determining the malignant phenotype that makes cancer cells
more invasive and tumorigenic.
PMID- 9650563
TI - SP220K is a novel matrix serine proteinase.
AB - Matrix proteinases play a critical role in extracellular matrix remodeling, which
is particularly involved in cancer invasion and metastasis. We have previously
characterized and purified a new tetrameric serine proteinase (SP220K) from human
kidney clear cell carcinoma plasma membranes. Here, we report that SP220K
exhibits gelatinase activity as assessed both in solution and by zymography.
Optimum gelatinase activity ranges between pH 7.5 to pH 9.0. Fibronectin and type
I collagen were hydrolyzed by SP220K, at variance with laminin and type IV
collagen. Like other trypsin-like fibronectin degrading proteinases, SP220K
released the 29-kDa N-terminal heparin-binding domain of fibronectin. By using a
panel of proteinase inhibitors, we found that the inhibition profile of SP220K
was different from that of other known serine proteinases such as thrombin,
trypsin, plasmin, plasminogen activators and tryptase. Altogether, our results
indicate that SP220K corresponds to a novel matrix proteinase that exhibits a
marked specificity for fibronectin and type I collagen.
PMID- 9650564
TI - 12(S)-hydroxyeicosatetraenoic acid increases the actin microfilament content in
B16a melanoma cells: a protein kinase-dependent process.
AB - 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], a lipoxygenase metabolite of
arachidonic acid, has been shown to be involved in a wide variety of cellular
activities (i.e., adhesion, spreading, motility, invasion) which promote
metastasis to occur in tumor cells. In this study, several techniques (Western
blotting, flow cytometry and DNase I assay) were performed to examine the
alterations in the distribution of G- and F-actin expressed in B16a melanoma
cells. Each of these methods independently revealed that 12(S)-HETE treatment
(0.1 mM, 15 min) resulted in an increase in the F-actin content in the
cytoskeletal preparations. Since the integrity of cytoskeletal networks (i.e.,
actin filaments) can be dynamically regulated through protein phosphorylation, we
investigated the potential role of several protein kinases in the 12(S)-HETE
induced actin polymerization. By flow cytometric analysis, 12(S)-HETE was found
to increase the actin filament contents. This effect could be inhibited by
protein kinase C (PKC) inhibitors (calphostin C and staurosporine) as well as by
protein tyrosine kinase (PTK) inhibitor (genistein) but not by protein kinase A
inhibitor (H8), suggesting that the 12(S)-HETE effect involves PKC and PTK. This
conclusion is consistent with the observations that phorbol 12-myristate-13
acetate (PMA) mimics the biological effect of 12(S)-HETE in promoting the F-actin
formation in B16a cells. As a final analysis, direct protein phosphorylation
studies indicate that 12(S)-HETE treatment led to enhanced phosphorylation of
myosin light chain, which may contribute to the increased stress fiber formation
following 12(S)-HETE stimulation.
PMID- 9650565
TI - Effect of a newly developed bisphosphonate, YH529, on osteolytic bone metastases
in nude mice.
AB - YH529, [1-hydroxy-2-(imidazo [1,2-a] pyridin-3-yl) ethylidene]-bisphosphonic acid
monohydrate, is a newly developed third-generation bisphosphonate with a potent
inhibitory activity toward osteoclastic bone resorption. The primary cellular
mechanism of osteolysis associated with metastatic cancer is osteoclast-mediated.
It is likely that bisphosphonates would be efficacious in this situation. In the
present study, we examined the effect of YH529 in a nude mice bone metastasis
model, in which the intracardiac injection of a human breast cancer cell line,
MDA-MB-231 (MDA-231), leads to osteolytic bone metastases. To examine whether
YH529 would prevent such bone metastasis, we administered YH529 s.c. to nude mice
simultaneously with cancer cell inoculation through the entire experimental
period (protocol 1) or performed short-term prophylactic administration before
inoculation of the MDA-231 cells (protocol 2). In addition, to examine the
possible therapeutic effects of the drug on established bone metastases, we
injected YH529 after radiographically small but distinct osteolytic bone
metastases had been detected (protocol 3). In all protocols, YH529 (2
microg/mouse/day) markedly inhibited bone metastases as well as the progression
of established metastatic foci that were quantified on the radiographs.
Histological examination and histomorphometrical analysis revealed that YH529
markedly reduced the number of osteoclasts and the size of the tumor at the
metastatic bone sites. Our results suggest that YH529 may suppress metastasis
formation and tumor growth in bone through inhibition of osteoclastic bone
resorption.
PMID- 9650566
TI - Fasting/re-feeding before initiation enhances the growth of aberrant crypt foci
induced by azoxymethane in rat colon and rectum.
AB - In contrast to the protective effect of chronic caloric restriction on tumor
development, we have shown that fasting sustained tumor initiation in rat liver
by a noninitiating dose of diethylnitrosamine. Here we investigated whether
fasting had a similar favorable effect on initiation in the colorectal mucosa in
80 male F344 rats. Animals fasted for 4 days were given a single s.c. dose of
azoxymethane (AOM) (20 mg/kg) on the first day of re-feeding, and rates of
kinetic proliferative parameters, and development of the pre-neoplastic lesions
such as aberrant crypt foci (ACF), were evaluated. Starvation before AOM
treatment enhanced the growth of ACF, as shown by the significantly higher crypt
multiplicity of fasted/re-fed rats as compared with fully fed rats (3.97 +/- 0.50
vs. 2.64 +/- 0.20, p < or = 0.025). This difference was associated with
perturbations in cell death and cell proliferation. Fasting induced apoptosis and
depressed cell division, while re-feeding had opposite effects, resulting in a
higher percentage of S-phase cells at the time of AOM injection and 2 days
thereafter. Starvation-induced apoptosis may represent the mitogenic stimulus to
an increase in the number of cells susceptible to AOM damage, and may favor its
fixation, leading to enhanced growth of ACF. Our data therefore suggest that
fasting/re-feeding enhances colon cancer.
PMID- 9650567
TI - Extracellular matrix modulates expression of growth factors and growth-factor
receptors in liver-colonizing colon-cancer cell lines.
AB - Site-specific metastasis is determined by the extracellular matrix (ECM) of the
colonized organ. We have shown that hepatocyte-derived ECM stimulated
proliferation of colon-cancer cells via induction of autocrine growth factors and
their receptors. The ECM component responsible was heparin proteoglycan. We
therefore investigated the effect of exogenously added heparin on colon cell
lines of varying liver-colonizing potential. The cells were grown on typical
liver matrix components, such as fibronectin and collagens type I and IV. We
assessed the effect of these matrix components on clonal growth, proliferation
and expression of autocrine growth factors and their receptors. The clonal growth
of the KM12 cells was not affected by heparin, while the other cell lines were
inhibited by heparin. Cell proliferation in weakly metastatic KM12, but not in
strongly metastatic KM12SM, was inhibited by heparin on plastic. Weakly
metastatic LS174T, but not strongly metastatic LiM6, was inhibited by heparin on
fibronectin. Expression of erb-B2 was also differently modulated by heparin in
weakly metastatic vs. highly metastatic cells. In weakly metastatic cells,
heparin reduced erb-B2 levels when cells were on plastic and fibronectin, while
in strongly metastatic cells, erb-B2 was induced by heparin. In all 4 cell lines,
mRNA for cripto was induced by heparin when the cells were grown on fibronectin.
In KM12SM cells, amphiregulin was induced by heparin in cells on fibronectin and
collagen IV. We show that soluble heparin, similar in its carbohydrate chemistry
to liver heparin proteoglycan, regulates the growth of colon-cancer cells. This
effect depends on other matrix components found in the liver and is mediated in
part by EGF family members.
PMID- 9650568
TI - Chemoprevention by N-acetylcysteine of urethane-induced clastogenicity and lung
tumors in mice.
AB - A major goal in pre-clinical cancer chemoprevention research is to assess the
predictive value of intermediate biomarker modulation towards tumor prevention.
With this aim, BALB/c mice were treated with 10 daily i.p. injections of urethane
(ethyl carbamate), each of 400 mg/kg body weight. Groups of mice received with
drinking water either a drug containing the thiol N-acetylcysteine (NAC), at 0.1
or 0.5 g/kg body weight, or its excipient, starting 27 days before the first
injection of the carcinogen until the end of the experiment. Out of the 30 mice,
10 per group were identified and individually monitored for 8 sequential times in
order to assess the course of micronucleated normochromatic erythrocytes in
peripheral blood. This systemic genotoxicity biomarker increased during the 10
day period of treatment with urethane, reached a peak 2 to 6 days after the last
injection, and was still significantly higher than the baseline after 10
additional days. Clastogenicity was significantly inhibited by NAC, with a dose
related effect, but not by the drug excipient. As evaluated 4 months after the
first injection of urethane, most mice developed lung tumors, whose multiplicity
was not affected by the drug excipient but was significantly decreased in the
presence of NAC. Correlation between the frequency of micronucleated
normochromatic erythrocytes at peak levels and lung-tumor multiplicity was highly
significant when evaluated in the context of all 40 mice undergoing cytogenetic
analyses (r = 0.561, p = 0.0002). It was similarly high, but did not reach the
significance threshold, within each treatment group, due to the lower number of
animals and some deviations from the regression line. Therefore, the prediction
of lung-tumor yield based on the intensity of the early genotoxicity biomarker is
justified when formulated within a sufficiently large group of animals, but is
not absolute at individual level.
PMID- 9650569
TI - Expression of Ly-6, a marker for highly malignant murine tumor cells, is
regulated by growth conditions and stress.
AB - Ly-6E.1 is highly expressed in murine tumor cells with a high malignancy
phenotype and may serve as a marker for such a phenotype. In this study, we
examined the effects of various growth conditions and stress on the expression
levels of Ly-6E.1 by tumor cells. Previous preliminary results have shown that
murine DA3 mammary tumor cells expressing high levels of Ly-6E.1 (Ly-6(hi)) are
more highly tumorigenic than the same tumor cells expressing low levels of this
membrane protein (Ly-6(lo)). In this study, we demonstrate that mice bearing Ly
6(hi) DA3 tumors have a significantly higher burden of spontaneous pulmonary
metastasis than mice bearing Ly-6(lo) DA3 tumors. Furthermore, the survival time
of the former mice was significantly shorter than that of the latter ones. We
further show that certain other members of the Ly-6 gene family such as Ly-6C.1
and Ly-6G.1 are coregulated with Ly-6E.1. This was shown to occur with respect to
both DA3 cells as well as A3 tumor cells which are of fibroblast origin. However,
these 2 cells differ with respect to regulation of Sca-2 (TSA1, another member of
the Ly-6 family) expression on these cells. Levels of Sca-2 on A3 cells appear to
be coregulated with Ly-6E.1 (i.e., Ly-6(hi) A3 cells express high levels of Sca-2
and Ly-6(lo) A3 cells express low levels of Sca-2). These 2 Ly-6 proteins were,
however, not coregulated on DA3 cells. Both Ly-6(hi) as well as Ly-6(lo) DA3
cells express equal levels of Sca-2. Levels of Thy-1, another
glycosylphosphatidylinositol (GPI)-anchored protein expressed by A3 tumor cells,
were equally expressed by both Ly-6(hi) and Ly-6(lo) A3 tumor cells. Levels of Ly
6 (but not those of CD44) on A3 tumor cells were upregulated on cells from dense
cultures but were not influenced by the position of the cells in the cell cycle.
Stress conditions such as serum starvation or heat shock upregulated the
expression of Ly-6 by the 2 types of tumor cells but did not induce apoptosis in
these cells. The kinetics of the stress-dependent upregulation of Ly-6 expression
differed, however, between the epithelial and fibroblastic tumor cells.
PMID- 9650570
TI - Prevalence of respiratory symptoms and increased specific IgE levels in West
African workers exposed to isocyanates.
AB - Respiratory symptoms and immunological effects from chronic exposure to
isocyanates (toluene diisocyanate) were studied in a cross survey of workers from
West African factories producing paints and polyurethane foam. A questionnaire, a
pulmonary function test, immunoglobulin E (IgE) levels, radioallergosorbent test
(RAST) and an atmospheric sample to quantify isocyanate exposures were carried
out in the workplace for each worker. Ninety-six workers, of whom 44 had
occupational isocyanate-induced asthma, were included in the study. Twenty-four
viral-infected subjects were excluded from the immunological study. Specific
antibodies to isocyanates were detected in two of the symptomatic individuals.
This low proportion appeared to be a common feature of this disease. The
prevalence of isocyanate-induced asthma in a West African working population
appears to be significant in the context of chronic human exposure, as current
data are based on excessive acute exposure due to an accident as seen in India.
PMID- 9650571
TI - Multigenerational study of the effects of consumption of PCB-contaminated carp
from Saginaw Bay, Lake Huron, on mink. 1. Effects on mink reproduction, kit
growth and survival, and selected biological parameters.
AB - This study was conducted to determine the multigenerational effects of
consumption of PCB-contaminated carp (Cyprinus carpio) from Saginaw Bay (Lake
Huron) on mink (Mustela vison) reproduction and health and to examine selected
biomarkers as potential indicators of polyhalogenated hydrocarbon toxicity in
mink. The mink were fed diets formulated to provide 0 (control), 0.25, 0.5, or
1.0 ppm polychlorinated biphenyls (PCBs) through substitution of Saginaw Bay carp
for ocean fish in the diets. To determine whether the effects of PCB exposure
were permanent, half of the parental (P1) animals were switched from their
respective treatment diets to the control diet after whelping the first of two F1
generations. Effects of in utero and lactational exposure to PCBs on subsequent
reproductive performance of the F1 animals were examined by switching half of the
first-year F1 offspring (kits) to the control diet at weaning, while the other
half was continued on their parental diet (continuous exposure). Continuous
exposure to 0.25 ppm, or more, of PCBs delayed the onset of estrus (as determined
by vulvar swelling and time of mating) and lessened the whelping rate. Litters
whelped by females continually exposed to 0.5 ppm, or more, of PCBs had greater
mortality and lesser body weights than controls. Continuous exposure to 1.0 ppm
PCBs had a variable effect on serum T4 and T3 concentrations. Compared to the
controls, there were significant differences in kidney, liver, brain, spleen,
heart, and thyroid gland weights of the mink continually exposed to 1.0 ppm PCBs.
There was an increase in the incidence of periportal and diffuse vacuolar
hepatocellular lipidosis in the P1 mink with continuous exposure to increasing
concentrations of PCBs. Plasma and liver PCB concentrations of the adult and kit
mink were, in general, directly related to the dietary concentration of PCBs and
the duration and time of exposure. Short-term parental exposure to PCBs had
detrimental effects on survival of subsequent generations of mink conceived
months after the parents were placed on "clean" feed. The lowest observed adverse
effect level (LOAEL) for dietary PCBs in this study was 0.25 ppm.
PMID- 9650572
TI - Multigenerational study of the effects of consumption of PCB-contaminated carp
from Saginaw Bay, Lake Huron, on mink. 2. Liver PCB concentration and induction
of hepatic cytochrome P-450 activity as a potential biomarker for PCB exposure.
AB - This study examined the effect of polychlorinated biphenyls (PCBs) from Saginaw
Bay (Lake Huron) carp on the hepatic cytochrome P-450 activity in mink (Mustela
vison). Hepatic cytochrome P-450 activities are of interest for their possible
use as biomarkers to indicate consumption and biological effects of PCBs in the
environment. Adult mink were fed diets containing ocean fish (control diet, 0.0
ppm) or Saginaw Bay carp toprovide 0.25, 0.5, or 1.0 ppm PCBs. Mink were bred
after 3 mo of exposure, and half of the parental mink (P1) and kits (F1-1)
previously consuming diets containing Saginaw Bay carp were switched to control
diet at weaning of the F1-1 kits. P1 and F1-1 mink were then bred within their
age and dietary groups after 15 mo of exposure, to produce the second-year F1 (F1
2) and F2 kits. Mink were killed when the new kits were weaned. Transfer of half
the animals to the control diet examined whether the effects of the PCB
containing diet on hepatic cytochrome P-450 activity were permanent. Continual
exposure to diets containing PCBs from Saginaw Bay carp induced cytochrome P-450
activity in a generally dose-dependent manner. Cytochrome P-450 activity was not
different from untreated controls in animals switched to the control diet from
the PCB-containing diet. The response of cytochrome P-4501A1 (EROD) activity in a
dose-dependent manner and the lack of induction after transfer to noncontaminated
diets suggest that this hepatic enzyme activity is a potential biomarker for
current exposure to PCBs and other similar cytochrome P-450 inducers.
PMID- 9650573
TI - Multigenerational study of the effects of consumption of PCB-contaminated carp
from Saginaw Bay, Lake Huron, on mink. 3. Estrogen receptor and progesterone
receptor concentrations, and potential correlation with dietary PCB consumption.
AB - Mink (Mustela vison) were fed diets containing ocean fish (control diet, 0.0 ppm
polychlorinated biphenyls, PCBs) or Saginaw Bay carp to provide 0.25, 0.5, or 1.0
ppm PCBs to examine the effect of PCBs on homeostasis of binding sites for
ovarian steroid hormones. Ranch-raised mink fed Great Lakes fish contaminated
with PCBs, or treated with PCBs directly, have demonstrated reproductive
impairment including anovulation, fetal resorption, delayed ovulation, increased
gestation, and decreased litter size. Previous studies have demonstrated that
estrogen and progesterone levels are unaltered in mink treated with PCBs,
suggesting that the effect of PCBs on reproduction is not mediated through
alterations in hormone homeostasis. In vitro studies have demonstrated that the
most likely means by which PCBs exert antiestrogenic ability is through a down
regulation of the estrogen receptor in normally estrogen-responsive tissues such
as liver and uterus. Hepatic and uterine estrogen binding site concentrations
were measured in female mink consuming diets containing PCBs for up to 18 mo at
up to 1 ppm. Hepatic estrogen binding site concentrations generally decreased
with increasing dietary PCB concentrations. Uterine estrogen binding site
concentration did not decrease in these animals. Uterine progesterone receptor
concentration also did not change with increasing PCB consumption. In total, the
response of hepatic and uterine estrogen and uterine progesterone binding sites
in mink fed diets containing Saginaw Bay carp suggests that concentrations of
PCBs available to uterine tissue may not have been sufficient to decrease uterine
estrogen receptor, despite their effect on hepatic estrogen receptor.
PMID- 9650574
TI - Acute effects of a bicyclophosphate neuroconvulsant on monoamine neurotransmitter
and metabolite levels in the rat brain.
AB - Naive male Sprague-Dawley rats were injected intraperitoneally (i.p.) with the
bicyclophosphate convulsant trimethylolpropane phosphate (TMPP) at dose levels
from 0.2 to 0.6 mg/kg. Rats were observed for convulsive activity, and were
sacrificed 15 min posttreatment. Levels of the monoamine neurotransmitters
norepinephrine (NE), epinephrine (EPI), dopamine (DA), and serotonin (5-HT) and
the major metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid
(HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in forebrain,
midbrain, hindbrain, cerebellum and brainstem regions. Neurotransmitter and
metabolite levels were compared between control rats and rats that did and did
not experience seizures. TMPP administration induced significant decreases in
levels of measured neurotransmitters that varied as a function of brain region,
dose, and expression of the seizure activity. These results show that tonic or
tonic-clonic seizures induced by TMPP administration (0.6 mg/kg) are reliably
associated with regional decreases in serotonin, dopamine, and norepinephrine.
Convulsive activity resulting from lower dose administrations (0.2-0.4 mg/kg) of
TMPP result only in decreased regional levels of serotonin.
PMID- 9650575
TI - Substrate inhibition of cruzipain is not affected by the C-terminal domain.
AB - Endogenous and recombinant cruzipain, the major cysteine proteinase from the
protozoan parasite Trypanosoma cruzi, exhibit differences in the protein and
circular dichroism spectra probably attributed to the absence of the C-terminal
domain in the recombinant enzyme. Substrate hydrolysis of both molecules at 25
degrees C and neutral pH obeyed Michaelis-Menten kinetics whereas significant
substrate inhibition was observed above neutral pH. The results suggest that
substrate inhibition of cruzipain is pH-dependent, and that the C-terminal domain
does not play an essential role in this process.
PMID- 9650576
TI - BEN1 and ZEN1 cDNAs encoding S1-type DNases that are associated with programmed
cell death in plants.
AB - We describe the isolation and characterization of cDNAs encoding two DNases that
may be involved in the programmed death of plant cells: a 35-kDa nuclease of
barley, which had been reported to be secreted from the aleurone layer into the
endosperm during germination and may be responsible for the digestion of nuclear
DNA in the course of degradation (cell death) of endosperm, and a 43-kDa nuclease
of zinnia, which appears transiently in association with differentiation to
tracheary elements and is likely to participate in the autolysis at the final
step of the differentiation. Genes for these nucleases of barley and zinnia were
designated BEN1 and ZEN1, respectively. The amino acid sequence of BEN1 protein
deduced from the nucleotide sequence of BEN1 cDNA consisted of 288 residues with
a putative signal sequence of 23 residues. RNA gel blot analysis revealed that
BEN1 mRNA increased in the embryo-less half seeds of barley in response to the
application of gibberellic acid. The deduced amino acid sequence of ZEN1 protein
consisted of 303 residues with a putative signal sequence of 25 residues.
Temporal accumulation of ZEN1 mRNA was detected during transdifferentiation of
zinnia mesophyll cells into tracheary elements. Significant similarities were
found among the amino acid sequences of BEN1, ZEN1, nuclease S1 from Aspergillus
oryzae, and two other S1-type nucleases.
PMID- 9650577
TI - Activation of the A2A adenosine receptor inhibits nitric oxide production in
glial cells.
AB - Selective adenosine receptor agonists and antagonists have marked effects on the
outcome of cerebral ischemia, and adenosine receptors are expressed on
astrocytes. In this study we examined the effects of various adenosine receptor
agonists on the production of nitric oxide and the induction of iNOS in
astrocytes activated by LPS/IFN-gamma and TNF-alpha/IL-1beta and on the
production of TNF-alpha. Treatment of the cells with the A2A receptor agonist CGS
21680 inhibited both NO production and iNOS expression induced by stimulation
with either LPS/IFN-gamma or TNF-alpha/IL-1beta, whereas the A1 and A3 receptor
agonists, CPA and Cl-IB-MECA, respectively, did not have significant inhibitory
effects. The inhibitory effect of the A2A receptor agonist was antagonized by the
specific A2A receptor antagonist CSC. The A2A agonist also exerted a small
inhibitory effect on the production of TNF-alpha. Similar inhibitory effects on
the production of NO were obtained by cyclic AMP-elevating reagents, such as
forskolin and dibutyryl cyclic AMP. Our findings suggest that activation of the
A2A receptor inhibits NO production and iNOS expression likely via increased
cAMP.
PMID- 9650578
TI - Potent inhibition of specific diadenosine polyphosphate hydrolases by suramin.
AB - The cytosolic enzymes asymmetrical diadenosine tetraphosphate hydrolase (EC
3.6.1.17, Ap4Aase) and diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap3Aase)
are inhibited competitively by suramin. Ap4Aase and Ap3Aase were assayed in
cytosolic rat brain extracts using fluorogenic analogues of the respective
substrates diadenosine tetraphosphate (Ap4A) and diadenosine triphosphate (Ap3A).
Ki values for suramin as inhibitor of Ap4Aase and Ap3Aase were 5 x 10(-6) M and 3
x 10(-7) M, respectively. Results indicate that suramin or suramin-like
derivatives may be useful tools to investigate diadenosine polyphosphate cleaving
enzymes and that the intracellular diadenosine polyphosphate metabolism may be a
pharmacological target of suramin with biological and clinical implications.
PMID- 9650579
TI - The role of transient starch in acclimation to elevated atmospheric CO2.
AB - Although increased concentrations of CO2 stimulate photosynthesis, this
stimulation is often lost during prolonged exposure to elevated carbon dioxide,
leading to an attenuation of the potential gain in yield. Under these conditions,
a wide variety of species accumulates non-structural carbohydrates in leaves. It
has been proposed that starch accumulation directly inhibits photosynthesis, that
the rate of sucrose and starch synthesis limits photosynthesis, or that
accumulation of sugars triggers changes in gene expression resulting in lower
activities of Rubisco and inhibition of photosynthesis. To distinguish these
explanations, transgenic plants unable to accumulate transient starch due to leaf
mesophyll-specific antisense expression of AGP B were grown at ambient and
elevated carbon dioxide. There was a positive correlation between the capacity
for starch synthesis and the rate of photosynthesis at elevated CO2
concentrations, showing that the capability to synthesize leaf starch is
essential for photosynthesis in elevated carbon dioxide. The results show that in
elevated carbon dioxide, photosynthesis is restricted by the rate of end product
synthesis. Accumulation of starch is not responsible for inhibition of
photosynthesis. Although transgenic plants contained increased levels of hexoses,
transcripts of photosynthetic genes were not downregulated and Rubisco activity
was not decreased arguing against a role of sugar sensing in acclimation to high
CO2.
PMID- 9650581
TI - 31P NMR study of the interactions between oligodeoxynucleotides containing (6-4)
photoproduct and Fab fragments of monoclonal antibodies specific for (6-4)
photoproduct.
AB - A 31P nuclear magnetic resonance (NMR) study of the interactions between
oligonucleotides containing the (6-4) photoproduct and the Fab fragments of
monoclonal antibodies (64M3 and 64M5) recognizing the (6-4) photoproduct is
reported. The 31P chemical shift data indicate that backbone conformation of (64)
adduct is affected by the presence of flanking oligodeoxynucleotides, and (6-4)
adducts with different backbone conformations are accommodated in the antigen
binding sites of these antibodies. It was also revealed that epitopes for these
antibodies consist of not only the (6-4) adduct but the flanking di- or tri
deoxynucleotides on both the 5' and 3' sides as well.
PMID- 9650580
TI - 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist:
identification as one of the major species of monoacylglycerols in various rat
tissues, and evidence for its generation through CA2+-dependent and -independent
mechanisms.
AB - The molecular species compositions of monoacylglycerols obtained from various rat
tissues were examined by reverse-phase high-performance liquid chromatography
(HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses. We confirmed
that 2-arachidonoylglycerol, an endogenous cannabinoid receptor agonist, is one
of the most abundant molecular species of monoacylglycerols in the brain.
Substantial amounts of 2-arachidonoylglycerol were also found in the liver,
spleen, lung and kidney, but the levels were considerably lower than that in the
brain. We found that a small amount of 2-arachidonoylglycerol was generated in a
brain homogenate during incubation in the absence of Ca2+. Importantly, the
generation of 2-arachidonoylglycerol was markedly augmented in the presence of
Ca2+, suggesting that Ca2+ plays a key role in regulation of the generation of 2
arachidonoylglycerol in this tissue.
PMID- 9650582
TI - Different degradation pathways for heterologous glycoproteins in yeast.
AB - Rat nerve growth factor receptor ectodomain (NGFRe) and Escherichia coli beta
lactamase were translocated into the yeast endoplasmic reticulum (ER),
glycosylated, misfolded and rapidly degraded. NGFRe underwent ATP-dependent
thermosensitive degradation independently of vesicular transport. Since no
evidence for degradation by the cytoplasmic 26S proteosome complex could be
obtained, NGFRe appeared to be degraded in the ER. Beta-lactamase exited the ER
by vesicular traffic and was transported from the Golgi via the Vps10 receptor
pathway to the vacuole for degradation. Machineries in the ER and the Golgi
appear to recognize distinct structural features on misfolded heterologous
proteins and guide them to different degradation pathways.
PMID- 9650583
TI - Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play
a role in signaling from neuron to microglia?
AB - Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor
CX3CR1 was investigated in the rat brain. In situ hybridization study revealed
that fractalkine mRNA was dominantly expressed in neuronal cells particularly in
the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus
accumbens. In vitro study using enriched neuronal or glial culture supported the
dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1
mRNA was dominantly expressed in glial cells throughout the whole brain. The in
vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not
astrocytes or neurons. Fractalkine appears to function as a signal molecule from
neuron to microglia.
PMID- 9650584
TI - Topological and functional analysis of the rat liver carnitine
palmitoyltransferase 1 expressed in Saccharomyces cerevisiae.
AB - The rat liver carnitine palmitoyltransferase 1 (L-CPT 1) expressed in
Saccharomyces cerevisiae was correctly inserted into the outer mitochondrial
membrane and shared the same folded conformation as the native enzyme found in
rat liver mitochondria. Comparison of the biochemical properties of the yeast
expressed L-CPT 1 with those of the native protein revealed the same detergent
lability and similar sensitivity to malonyl-CoA inhibition and affinity for
carnitine. Normal Michaelis-Menten kinetics towards palmitoyl-CoA were observed
when careful experimental conditions were used for the CPT assay. Thus, the
expression in S. cerevisiae is a valid model to study the structure-function
relationships of L-CPT 1.
PMID- 9650585
TI - Identification of multispecific organic anion transporter 2 expressed
predominantly in the liver.
AB - In the present study, we demonstrate that NLT (novel liver-specific transport
protein) is a multispecific organic anion transporter of the liver. The amino
acid sequence of NLT shows 42% identity to that of the renal multispecific
organic anion transporter, OAT1. When expressed in Xenopus laevis oocytes, NLT
mediated uptake of organic anions, such as salicylate, acetylsalicylate, PGE2,
dicarboxylates and p-aminohippurate. [14C]Salicylate uptake via NLT was saturable
(Km = 88.8 +/- 23.4 microM) and sodium-independent. Expression of the mRNA of NLT
was detected in the liver and kidney (liver >> kidney). We propose that NLT be
renamed OAT2.
PMID- 9650586
TI - The carboxy-terminal region of adenovirus E1A activates transcription through
targeting of a C-terminal binding protein-histone deacetylase complex.
AB - Binding of the C-terminal binding protein, CtBP, to the adenovirus E1A moiety of
a Gal4-E1A fusion protein abolishes conserved region (CR) 1-dependent
transcription activation. In contrast, a non-promoter targeted E1A peptide,
capable of binding CtBP, can induce transcription from the proliferating cell
nuclear antigen (PCNA) promoter. CtBP is shown here to bind the histone
deacetylase HDAC1, suggesting that a promoter targeted CtBP-HDAC1 complex can
silence transcription from the PCNA promoter through a deacetylation mechanism.
Expression of the CtBP binding domain of E1A is sufficient to alleviate
repression, possibly due to the displacement of the CtBP-HDAC1 complex from the
promoter.
PMID- 9650587
TI - A G.U base pair in the eukaryotic selenocysteine tRNA is important for
interaction with SePF, the putative selenocysteine-specific elongation factor.
AB - In Escherichia coli, selenocysteine biosynthesis and incorporation into
selenoproteins requires the action of four gene products, including the
specialized selenocysteine tRNA(Sec) and elongation factor SELB, different from
the universal EF-Tu. In this regard, the situation is less clear in eukaryotes,
but we previously reported the existence of SePF, a putative SELB homologue. The
secondary structure of the tRNA(Sec) differs slightly in eukaryotes, due to a
change in the lengths of several stems. Two non-Watson-Crick base pairs, G5a x
U67b and U6 x U67, reside in the acceptor stem and are conserved in the course of
evolution. Since it has already been reported that changing them to Watson-Crick
base pairs did not affect the serylation or selenylation levels of tRNA(Sec), we
asked whether these non-Watson-Crick base pairs are required for the interaction
with SePF. To this end, tRNA(Sec) variants carrying Watson-Crick changes at these
positions were tested for their ability to maintain the interaction with SePF. In
these assays, the tRNA(Sec)-SePF interaction was determined by the protective
action it confers against hydrolysis of the amino acid ester bond, under basic
conditions. All the changes introduced at U6 x U67 did not significantly affect
the interaction. Interestingly, however, the G5a x U67b to G5a-C67b substitution
was sufficient, by itself, to lead to unprotection of the ester bond. Therefore,
our finding strongly suggests that SePF is unable to interact with a tRNA(Sec)
mutant version carrying a Watson-Crick G5a-C67b instead of the wild-type G5a x
U67b base pair, establishing that G5a x U67b constitutes a structural determinant
for SePF interaction.
PMID- 9650588
TI - Purification and properties of exopolyphosphatase isolated from Saccharomyces
cerevisiae vacuoles.
AB - An exopolyphosphatase (polyPase) with a specific activity of 60 U/mg protein has
been purified from the vacuolar sap of Saccharomyces cerevisiae. The molecular
mass of the intact enzyme was found to be 245 kDa. It is highly specific towards
high-molecular polyphosphates (polyP). The activity with polyP9 is 24% of that
with polyP208. The apparent Km for polyP15 and polyP208 hydrolysis is 93 and 2.4
microM, respectively. The enzyme is slightly active with polyP3 and adenosine-5'
tetraphosphate, but does not hydrolyze pyrophosphate, ATP, GTP and p
nitrophenylphosphate. It is stimulated by divalent metal cations. Co2+, the best
activator, stimulates it 6-fold. Antibodies that inhibit the cell envelope and
cytosol polyPases of S. cerevisiae have no effect on the vacuolar polyPase. The
vacuolar polyPase differs from other yeast polyPases in molecular mass, substrate
specificity and effects of activators.
PMID- 9650589
TI - Coupling of proton source and sink via H+-migration along the membrane surface as
revealed by double patch-clamp experiments.
AB - Long-range proton transfer along the surface of black lipid bilayers was observed
between two integral membrane channels (gramicidins), one operating as a proton
source, the other as a sink, by patch-clamp technique. In contrast, potassium
ions were shown to equilibrate with the aqueous bulk phase before being consumed.
Both channels opened and closed simultaneously only if the charge between them
was carried by protons. In this case an anomalous high conductance between two
patched membrane fragments was measured, each of them containing one single
gramicidin channel. The coupled state disappeared when the distance between these
two channels was increased above the critical value. The latter was shown to
increase with the channel lifetime. Our results support the idea of the
'localized' proton coupling, in which protons that have been pumped across
membranes migrate along the membrane surface to reach another membrane protein
that utilizes the established pH gradient.
PMID- 9650590
TI - Identification of an uncoupling mutation affecting the b subunit of F1F0 ATP
synthase in Escherichia coli.
AB - A specific b subunit arginine, b(Arg-36) in Escherichia coli, displays
evolutionary conservation among bacterial F1F0 ATP synthases. Site-directed
mutagenesis was used to generate a collection of mutations affecting b(Arg-36).
The phenotype differed depending upon the substitution, and the b(Arg-36-Glu) and
b(Arg-36-Ile) substitutions virtually abolished enzyme function. Although the
total amounts of F1F0 ATP synthase present in the membranes prepared from mutant
strains were reduced, the primary effect of the b(Arg-36) substitutions was on
the activities of the intact enzyme complexes. The most interesting result was
that the b(Arg-36-Glu) substitution results in the uncoupling of a functional F0
from F1 ATP hydrolysis activity.
PMID- 9650591
TI - T-cadherin and signal-transducing molecules co-localize in caveolin-rich membrane
domains of vascular smooth muscle cells.
AB - Cadherins are a family of cellular adhesion proteins mediating homotypic cell
cell binding. In contrast to classical cadherins, T-cadherin does not possess the
transmembrane and cytosolic domains known to be essential for tight mechanical
coupling of cells, and is instead attached to the cell membrane by a
glycosylphosphatidylinositol (GPI) anchor. This study explores the hypothesis
that T-cadherin might function as a signal-transducing protein. Membranes from
human and rat vascular smooth muscle cells were fractionated using Triton X-100
solubilization and density gradient centrifugation techniques. We demonstrate
that T-cadherin is enriched in a minor detergent-insoluble low-density membrane
domain and co-distributes with caveolin, a marker of caveolae. This domain was
enriched in other GPI-anchored proteins (CD-59, uPA receptor) and signal
transducing molecules (G alpha s protein and Src-family kinases), but completely
excluded cell-cell and cell-matrix adhesion molecules (N-cadherin and beta1
integrin). Coupling of T-cadherin with signalling molecules within caveolae might
enable cellular signal transduction.
PMID- 9650592
TI - Crystal structure of domain E of Thermus flavus 5S rRNA: a helical RNA structure
including a hairpin loop.
AB - The synthetic RNA fragment 5'-CUGGGCGG(GCGA)CCGCCUGG (nucleotides in parentheses
indicate the loop region) corresponds to the natural sequence of domain E from
nucleotides 79-97 of the Thermus flavus 5S rRNA including a hairpin loop. The RNA
structure determined at 3.0 A and refined to an R-value of 24.1% also represents
the first X-ray structure GNRA tetraloop. The loop is in distinctly different
conformation from other GNRA tetraloops analyzed by NMR. The conformation of the
two molecules in the asymmetric unit is influenced and stabilized by specific
intermolecular contacts. The structural features presented here give evidence for
the ability of RNA molecules to adapt to specific environments.
PMID- 9650593
TI - Role of copper during carbon monoxide binding to terminal oxidases.
AB - Under fully reduced conditions, reassociation kinetics of CO were studied in
several terminal oxidases containing copper in their binuclear center. The
purified Paracoccus denitrificans ba3-type quinol oxidase was found to recombine
with CO monophasically (tau 25-30 ms) like oxidases of the bo type from
Escherichia coli, the caa3 type from Bacillus halodurans FTU, and the bo type
from Methylobacillus flagellatum KT. Oxidase of the aa3 type from bovine heart
recombined with CO monophasically at a higher rate (tau 16-19 ms) than the
studied copper-containing bacterial oxidases. After prolonged incubation in the
presence of CO, oxidases of the ba3 and aa3 types changed their CO-binding
properties. The contribution of the slow component was diminished while new fast
components arose. Measurement of the metal content in the oxidases indicated that
during the incubation, the enzymes lost their copper, the process being
accompanied by the appearance of a fast CO recombination rate resembling that of
the non-copper oxidases of the bd type from E. coli and the bb type from Bacillus
halodurans FTU. This points to a role of copper in CO binding by terminal
oxidases.
PMID- 9650594
TI - Publication of negative results is an essential part of the scientific process.
PMID- 9650595
TI - Proteolysis of poly(ADP-ribose) polymerase by caspase 3: kinetics of cleavage of
mono(ADP-ribosyl)ated and DNA-bound substrates.
AB - Poly(ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme which is
responsible for synthesis of poly(ADP-ribose) in response to DNA damage caused by
numerous agents and during DNA base excision repair. After DNA damage, the enzyme
binds to nicks in DNA through its N-terminal zinc fingers and catalyzes the
formation of poly(ADP-ribose) on various nuclear acceptors including itself. When
DNA damage is extensive, cells induce their own demise by activating the
proteases that induce apoptosis (caspases) which cleave PARP and other death
substrates. Here we report the development of a new approach to investigate the
sensitivity of mono(ADP-ribosyl)ated and DNA-bound PARP to cleavage during
apoptosis. The development of a stoichiometric labeling procedure of the enzyme
has allowed us to evaluate the catalytic properties of caspase 3 toward mono(ADP
ribosyl)ated PARP at various enzyme:substrate molar ratios. We show that low
levels of automodification (< or = 3 U of ADP-ribose per chain) do not inhibit
the proteolysis of the substrate. In addition, we demonstrate that binding of
unmodified PARP to DNA influences the kinetics of its cleavage by caspase 3.
PMID- 9650596
TI - Radiosensitivity in ataxia telangiectasia fibroblasts is not associated with
deregulated apoptosis.
AB - Ataxia telangiectasia (AT) is an autosomal recessive human disorder featuring
diverse clinical abnormalities including proneness to cancer and extreme
sensitivity to ionizing radiation. Although cells from AT patients exhibit faulty
activation of the p53 signal transduction pathway at early times after radiation
exposure, it has been proposed that high levels of DNA damage persisting in AT
cells may up-regulate p53 through an ATM-independent mechanism at late times
after irradiation, leading to cell death by apoptosis. In this study we
demonstrate that diploid skin fibroblast strains homozygous for the AT mutation
fail to up-regulate p53 protein at late times (< or = 48 h) after irradiation
with 60Co gamma rays. Moreover, exposure of normal and AT fibroblasts to a dose
of 8 Gy does not result in a significant increase in the fraction of apoptotic
cells. Since this treatment reduces the clonogenic potential of human cells by at
least two orders of magnitude, we conclude that apoptosis is not the primary
mechanism of cell death induced by ionizing radiation in human normal and AT
fibroblast cultures. Therefore, our results are not in accordance with the
current hypothesis suggesting that increased radiosensitivity of AT cells is
associated with deregulated apoptosis.
PMID- 9650597
TI - Comparison between pulsed-field gel electrophoresis and the comet assay as
predictive assays for radiosensitivity in fibroblasts.
AB - The radiosensitivity of skin fibroblasts derived from patients as measured in
vitro by a clonogenic survival assay appears to correlate with the risk of
developing severe late reactions to radiation. Unfortunately, these assays are
clinically impractical as a predictive test for radiosensitivity. The purpose of
this study was to assess the utility of two possible surrogate assays for
radiosensitivity, pulsed-field gel electrophoresis (PFGE) and single-cell gel
electrophoresis (comet assay), both of which can be used to measure DNA double
strand breaks. Twenty-three nontransformed human fibroblast cell lines exhibiting
a range of radiosensitivities were studied with both of these assays. The results
were correlated with measurements of radiosensitivity obtained as part of a
larger study examining the correlation between cellular radiosensitivity and
clinical response. [2-(14)C]Thymidine-labeled confluent cultures were irradiated
at 1.0 Gy/min with doses of 0 to 150 Gy. After allowing 4 h for repair at 37
degrees C, cells were trypsinized and aliquots were used for preparing slides for
the comet assay. After neutral lysis and electrophoresis, the slides were stained
with ethidium bromide and 50 comet moments were measured for each dose. The
remainder of the cells were formed into agarose plugs and, after neutral lysis,
were subjected to PFGE. The fraction of activity released (FAR) from the well was
measured by scintillation counting of appropriate segments of each gel lane.
Cellular radiosensitivity was measured with a standard clonogenic assay at a low
dose rate of 1.2 cGy/min, and the dose that resulted in a surviving fraction of
0.01 (D0.01) was calculated. The slope of the plot of comet moment as a function
of dose for each cell line did not correlate with D0.01 (R = 0.36, P > 0.1). In
contrast, the slope of the FAR as a function of dose had a weak inverse
correlation with D0.01 (R = 0.43 and P = 0.05) such that the more radiosensitive
cell lines exhibited a steeper dose response for FAR. Although the correlation
between the slope of the dose response for FAR and D0.01 was weak, refinement of
the PFGE technique may provide a potentially useful predictive assay for
radiosensitivity.
PMID- 9650598
TI - MYC mRNA abundance is unchanged in subcultures of HL60 cells exposed to power
line frequency magnetic fields.
AB - Epidemiological data have not demonstrated conclusively that there exists an
association between exposure to power-line frequency electric and magnetic fields
(EMFs) and cancer. Some laboratory studies performed to investigate possible
mechanisms for such an association reported biological effects of EMF exposure,
but attempts to confirm some such reports have had mixed success. The most
publicized experiments in this regard were studies on the purported EMF-induced
increase in MYC expression in HL60 cells. To address the accuracy and
reproducibility of this effect, HL60 cells were exposed to 6-microT 60 Hz
magnetic fields, and MYC expression was measured. Assay methods and exposure
conditions were as close as practical to those of the investigators that
originally reported a positive effect. A chemical agent was used to demonstrate
that the cells were responsive to a known stimulus and that the experimental
system was sufficiently sensitive to detect such a stimulus. The experimental
system had sufficiently low basal variability to allow the detection of effects
of the magnitude that had been reported previously. Using either cells from a
commercial source or cells supplied by the original investigators, no evidence
was obtained to support the hypothesis that EMF exposure could induce MYC
expression.
PMID- 9650599
TI - Transfection of a vector expressing wild-type p53 into cells of two human glioma
cell lines enhances radiation toxicity.
AB - Replication-deficient adenovirus (Adv5)-based vectors containing either wild-type
p53 or the beta-gal marker gene were introduced into cells of the T98G (p53
mutant) and U87MG (p53 wild-type) human glioma cell lines. The wild-type p53 gene
was successfully expressed in each cell line as shown by flow cytometry and
Western blotting. The presence of the p53-expressing vector was toxic in both
cell lines compared to control cells or to those containing the beta-gal vector.
At levels of Adv5p53 vector that produced detectable toxicity, the effect of
irradiation was enhanced, producing a twofold increase in cell killing. In the
T98G cells, the presence of the p53 vector resulted in an increase in the number
of cells undergoing apoptosis after irradiation, whereas a smaller and only
additive response was observed in the U87MG cells. Conversely, an increase in
micronucleus formation, indicating corrupt mitotic activity, was observed in
irradiated Adv5p53-positive U87MG cells but not in T98G cells. These data suggest
that p53-expressing vectors effectively enhance radiation lethality in these
human glioma cell lines, but that the mechanism of action cannot be simply
related to activation of the p53-dependent pathway to apoptosis.
PMID- 9650600
TI - Evaluation of lactate as a 1H nuclear magnetic resonance spectroscopy index for
noninvasive prediction and early detection of tumor response to radiation therapy
in EMT6 tumors.
AB - In a recent study (Int. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 1996), 1H
nuclear magnetic resonance (NMR) spectroscopy was used to demonstrate significant
decreases in lactate levels after gamma irradiation of radiosensitive RIF-1
tumors in vitro. For comparison, we have examined the effects of gamma radiation
on lactate levels in the more radioresistant EMT6 tumor. Single-slice (5-6 mm
thick) localized 1H spectra of subcutaneous RIF-1 (untreated) and EMT6 tumors
(pretreatment, 24 and 48 h postirradiation with 4, 10 or 20 Gy of gamma
radiation) were measured by the selective multiple quantum coherence transfer
method (Sel-MQC, approximately 4 min acquisition time). Both pretreatment lactate
levels and pretreatment lactate dehydrogenase (LDH) activities were found to be
similar in RIF-1 and EMT6 tumors, suggesting that steady-state lactate levels are
unlikely to be reliable indices for predicting response to radiation therapy.
After 10 Gy gamma irradiation, EMT6 tumors showed a 21% decrease relative to
pretreatment lactate levels at 48 h (1.04 +/- 0.22 to 0.82 +/- 0.16; P = 0.06);
after 20 Gy a 40% decrease was observed at 48 h (1.34 +/- 0.27 to 0.81 +/- 0.10;
P = 0.07). No significant changes in lactate levels were observed in control EMT6
tumors or in tumors treated with 4 Gy of gamma radiation, in contrast to changes
detected previously in RIF-1 tumors, which showed a significant decrease in
lactate by 48 h for both 2 and 4 Gy. The decreased effect of radiation on lactate
levels in EMT6 compared to RIF-1 tumors may be attributed to the higher hypoxic
fraction and lower radiosensitivity of EMT6 tumors (Int. J. Radiat. Oncol. Biol.
Phys. 10, 695-712, 1984). The decrease in lactate levels did not, however,
strictly reflect the extent of the response to therapy for the high dose of 20
Gy. This study together with our earlier study (Int. J. Radiat. Oncol. Biol.
Phys. 36, 635-639, 1996) provides evidence to support the hypothesis that changes
in steady-state tumor lactate levels may serve as sensitive early indices of
tumor response to gamma radiation at doses of the order of 2 to 4 Gy.
PMID- 9650601
TI - Effects of ionizing radiation (neutrons/gamma rays) on plasma lipids and
lipoproteins in rats.
AB - Male Wistar rats weighing 250 g were exposed to 4 Gy of neutrons/gamma radiation
(3.33 Gy of neutrons and 0.66 Gy of gamma rays). After whole-body irradiation,
plasma cholesterol and phospholipid levels increased up to 62 and 37%,
respectively, at day 4 and then returned to control values 12 days after
irradiation. Plasma triglyceride concentrations decreased concomitantly with
decreased food intake after irradiation but remained higher than in pair-fed
control rats. Plasma lipoproteins were separated by ultracentrifugation on a
density gradient (1.006-1.210 g/ml). Four days after irradiation, most of the
cholesterol (62% compared to 31% in controls, P < 0.001) is transported by
apolipoprotein E-rich high-density lipoproteins. At the same time, plasma levels
of apolipoproteins B and E were increased by 28 and 65%, respectively, while
those of apolipoproteins AI and AIV were reduced by 21 and 59%, respectively.
While in the liver of irradiated rats the apolipoprotein B/E receptor number was
not modified, the hydroxymethylglutaryl coenzyme A reductase activity was
fivefold higher than in control pair-fed rats. Four days after irradiation, the
susceptibility of lipoproteins to peroxidation, as measured by the formation of
conjugated dienes in the presence of Cu2+, was markedly increased while plasma
vitamin E levels were decreased, demonstrating that irradiation reduces
antioxidant stores markedly. These results suggest that such modified
lipoproteins could be involved in radiation-induced vascular damage.
PMID- 9650602
TI - Effects of gamma radiation on levels of brain metallothionein and lipid
peroxidation in transgenic mice.
AB - The induction of metallothionein (MT) synthesis in the brain was investigated in
MT-I isoform-overexpressing transgenic (MT-I*) and control mice after exposure to
increasing doses of 2 to 20 Gy of whole-body gamma radiation. Although the MT-I
isoform was the major isoform of MT in this transgenic mouse, the other isoforms,
MT-II and MT-III, were also present in the brain. The total concentration of MT
in the brain was measured by a cadmium-binding assay, while zinc and lipid
peroxides were measured by atomic absorption spectrophotometry and by the
thiobarbituric acid method, respectively. In MT-I* mice at 24 h after radiation
exposure, the level of MT in the brain was increased from a basal level of 44.4
+/- 4.0 microg/g to a maximum level of 91.0 +/- 9.0 microg/g after 5 Gy and
remained high after 10 and 20 Gy. In a time-course experiment with 5 Gy, the
concentration of MT in the brain of MT-I* mice increased at 3 h and reached a
maximum of 175.3 +/- 15.3 microg/g at 6 h. This high level of MT remained
unchanged for 48 h after radiation exposure. Metallothionein was not induced
markedly in the brains of control mice either at 24 h after exposure to 2-20 Gy
gamma radiation or at different times after exposure to 5 Gy gamma radiation. In
both strains of mice, the total concentration of zinc in the brain decreased with
increasing radiation dose. No differences in lipid peroxide levels were seen in
control mice exposed to 5 Gy at 6 and 12 h or after exposure to three other doses
(2, 10 and 20 Gy) at 24 h. Slight increases (1.35 and 1.22, respectively) in
lipid peroxide levels were observed in control mice at 24 and 48 h after exposure
to 5 Gy. Lipid peroxide levels in the brain were not changed in irradiated MT-I*
mice. The results show a marked increase in the levels of MT in the brain of
transgenic mice after exposure to gamma radiation. The induced synthesis of MT
may be only one of several mechanisms that prevent the induction of lipid
peroxidation in the brain by gamma radiation.
PMID- 9650603
TI - Radon-progeny exposure and lung cancer risk in a cohort of Newfoundland fluorspar
miners.
AB - Although radon is a well-established lung carcinogen, there are uncertainties
concerning the exposure-response relationship, whether exposures in early life
are particularly hazardous, and how smoking affects the risks associated with
radon exposure. A cohort study of the mortality experience of 1,743 underground
fluorspar miners and 321 surface workers from 1950 to 1984 reported previously
has been extended to include 6 additional years of follow-up (1985-1990). A
statistically significant relationship was noted between radon-progeny exposure
and risk of lung cancer mortality. Our analysis found no effect for age at first
exposure. Attained age was strongly predictive of excess relative risk (ERR) per
working level month (WLM) of radon exposure, falling from 0.025 for those aged
less than 50 years to 0.002 for those 70 years or older. An inverse exposure-rate
effect was also observed, wherein for equal total exposure, a high exposure rate
(and short duration) is less harmful than a low exposure rate (and long
duration). The ERR/WLM increased from 0.0019 for exposures of less than 10 years
to 0.0076 for exposures of 20 or more years. The analysis of time-since-exposure
windows revealed a greater ERR/WLM for exposures received in more recent periods,
similar to the result for time since last exposure. Excess relative risks per WLM
were higher for current smokers than for nonsmokers (never and former smokers).
Analyses were consistent with a multiplicative relationship between radon-progeny
exposure and current smoking and the risk of lung cancer. The assessment of radon
exposure and lung cancer risk should incorporate the effects of exposure rate,
time since exposure, smoking status and attained age.
PMID- 9650604
TI - Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2.
AB - Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at
the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest
National Laboratory (PNNL) were conducted. The hazard functions (age-specific
risks) for incidence of lung, bone and liver tumors were modeled as a function of
cumulative radiation dose, and estimates of lifetime risks based on the combined
data were developed. For lung tumors, linear-quadratic functions provided an
adequate fit to the data from both laboratories, and linear functions provided an
adequate fit when analyses were restricted to doses less than 20 Gy. The
estimated risk coefficients for these functions were significantly larger when
based on ITRI data compared to PNNL data, and dosimetry biases are a possible
explanation for this difference. There was also evidence that the bone tumor
response functions differed for the two laboratories, although these differences
occurred primarily at high doses. These functions were clearly nonlinear (even
when restricted to average skeletal doses less than 1 Gy), and evidence of
radiation-induced bone tumors was found for doses less than 0.5 Gy in both
laboratories. Liver tumor risks were similar for the two laboratories, and linear
functions provided an adequate fit to these data. Lifetime risk estimates for
lung and bone tumors derived from these data had wide confidence intervals, but
were consistent with estimates currently used in radiation protection. The dog
based lifetime liver tumor risk estimate was an order of magnitude larger than
that used in radiation protection, but the latter also carries large
uncertainties. The application of common statistical methodology to data from two
studies has allowed the identification of differences in these studies and has
provided a basis for common risk estimates based on both data sets.
PMID- 9650605
TI - The linear-quadratic model and most other common radiobiological models result in
similar predictions of time-dose relationships.
AB - One of the fundamental tools in radiation biology is a formalism describing time
dose relationships. For example, there is a need for reliable predictions of
radiotherapeutic isoeffect doses when the temporal exposure pattern is changed.
The most commonly used tool is now the linear-quadratic (LQ) formalism, which
describes fractionation and dose-protraction effects through a particular
functional form, the generalized Lea-Catcheside time factor, G. We investigate
the relationship of the LQ formalism to those describing other commonly discussed
radiobiological models in terms of their predicted time-dose relationships. We
show that a broad range of radiobiological models are described by formalisms in
which a perturbation calculation produces the standard LQ relationship for dose
fractionation/protraction, including the same generalized time factor, G. This
approximate equivalence holds not only for the formalisms describing binary
misrepair models, which are conceptually similar to LQ, but also for formalisms
describing models embodying a very different explanation for time-dose effects,
namely saturation of repair capacity. In terms of applications to radiotherapy,
we show that a typical saturable repair formalism predicts practically the same
dependences for protraction effects as does the LQ formalism, at clinically
relevant doses per fraction. For low-dose-rate exposure, the same equivalence
between predictions holds for early-responding end points such as tumor control,
but less so for late-responding end points. Overall, use of the LQ formalism to
predict dose-time relationships is a notably robust procedure, depending less
than previously thought on knowledge of detailed biophysical mechanisms, since
various conceptually different biophysical models lead, in a reasonable
approximation, to the LQ relationship including the standard form of the
generalized time factor, G.
PMID- 9650606
TI - Physical and biological interface dose effects in tissue due to X-ray-induced
release of secondary radiation from metallic gold surfaces.
AB - Dose enhancement up to more than a factor of 100 was found in an environment of
tissue-equivalent polymethylmethacrylate (PMMA) close to the surface of a thin
metallic gold foil. The enhancement factors were determined for heavily filtered
X rays (40 to 120 kV tube potential) under backscatter conditions, using thin
film radiation detectors with sub-micrometer resolution. The secondary electrons
were found to range up to some 10 microm in tissue-equivalent material.
Correspondingly, enhanced biological effects could be shown in vitro, using
monolayers of C3H 10T1/2 mouse embryo fibroblasts exposed in intimate contact
with the gold surface. The decay of the survival curves of cells irradiated on
gold was significantly steeper than for those obtained from irradiation between
PMMA disks with the same dose, also giving biological evidence for significantly
enhanced doses at the gold interface. The shape of the inactivation curves
resembled those for high-LET radiation, lacking a pronounced shoulder at the
lower doses. Quantitatively, doses of e.g. 50 mGy (80 kV X rays) in homogeneous
PMMA caused about 35% cell killing and 200 mGy about 80% when the cells were
irradiated at the gold surface. From a comparison of these inactivation numbers
with those found for irradiation between PMMA disks, biological dose enhancement
factors for the cell system considered ranged up to about a factor of 50. In
addition to cell inactivation, the in vitro irradiations of C3H 10T1/2 cells
adjacent to the gold surface resulted in increased rates of oncogenic
transformation. A dose of 100 mGy 80 kV X rays (measured in homogeneous PMMA)
caused a frequency at an inserted gold surface comparable to that obtained with a
dose of about 4.5 Gy of 60Co gamma rays in homogeneous PMMA.
PMID- 9650607
TI - Migration of electrons and holes in crystalline d(CGATCG)-anthracycline complexes
X-irradiated at 4 K.
AB - Electrons and holes generated in irradiated DNA migrate to stable trapping sites.
Protonation and deprotonation reactions at these sites promote the trapping of
electrons and holes, thereby inhibiting further migration. The extent of
migration determines the final distribution of damage in irradiated DNA. In this
study, electron and hole migration is investigated in a crystalline DNA hexamer
intercalated with an anthracycline drug. The intercalator is no further than 2
base pairs away from any DNA base. From EPR measurements, there is no evidence of
DNA-centered radicals in the irradiated DNA hexamer. The aromatic region of the
anthracycline intercalator evidently sequesters most or all of the electrons and
most of the holes. Further hole trapping and radical stabilization appear to
occur on the anthracycline's amino sugar group, which is nestled in the minor
groove of the hexamer. The relatively large yield of this proposed amino sugar
radical suggests that holes generated in the DNA solvation shell migrate to the
amino sugar, where they become trapped. This would be the first observation of a
radical formed by the direct effect of low-dose, low-LET radiation that is
trapped within the DNA helix, yet lies outside of the stacked bases. With respect
to holes generated in the DNA bases at 4 K, we conclude that most, if not all,
are capable of migrating to an intercalator < or = 2 base pairs away. With
respect to dry electrons, we conclude that anthracycline competes effectively for
electron trapping over a region of at least 2 base pairs; our experiments cannot
distinguish between electron attachment to the bases followed by transfer to the
intercalator and direct attachment to the intercalator.
PMID- 9650608
TI - The effects of delta rays on the number of particle-track traversals per cell in
laboratory and space exposures.
AB - It is a common practice to estimate the number of particle-track traversals per
cell or cell nucleus as the product of the ion's linear energy transfer (LET) and
cell area. This practice ignores the effects of track width due to the lateral
extension of delta rays. We make estimates of the number of particle-track
traversals per cell, which includes the effects of delta rays using radial
cutoffs in the ionization density about an ion's track of 1 mGy and 1 cGy.
Calculations for laboratory and space radiation exposures are discussed, and show
that the LET approximation provides a large underestimate of the actual number of
particle-track traversals per cell from high-charge and energy (HZE) ions. In
light of the current interest in the mechanisms of radiation action, including
signal transduction and cytoplasmic damage, these results should be of interest
for radiobiology studies with HZE ions.
PMID- 9650609
TI - Adaptive response in embryogenesis: I. Dose and timing of radiation for reduction
of prenatal death and congenital malformation during the late period of
organogenesis.
AB - An adaptive response was demonstrated during embryogenesis in mice. Whole-body
irradiation at a dose of 0-50 cGy was given to condition pregnant ICR mice on day
9 to day 11 of gestation. Then their whole bodies were exposed to a challenging
dose of 5 Gy on the next day. The numbers of living fetuses, prenatal deaths and
living fetuses with external gross malformations were determined on day 19. A
conditioning dose of 30 cGy on day 11 significantly increased the rate of living
fetuses and reduced the incidence of congenital malformations induced by a 5-Gy
dose on day 12. This indicates the existence of a critical dose and timing for
administering a conditioning dose for radioadaptation during the late period of
organogenesis in mice. The possible mechanisms involved are discussed.
PMID- 9650610
TI - Cancer cells under the fire of combined therapies.
PMID- 9650611
TI - New prodrug activation gene therapy for cancer using cytochrome P450 4B1 and 2
aminoanthracene/4-ipomeanol.
AB - Vector-mediated transfer of prodrug-activating genes provides a promising means
of cancer gene therapy. In a search for more selective and more potent
bioactivating enzymes for gene therapy of malignant brain tumors, the toxicity
generating capacity of the rabbit cytochrome P450 isozyme CYP4B1 was
investigated. Rabbit CYP4B1, but not rat or human isozymes, efficiently converts
the inert prodrugs, 2-aminoanthracene (2-AA) and 4-ipomeanol (4-IM), into highly
toxic alkylating metabolites. Toxicity of these two prodrugs was evaluated in
culture in parental and genetically modified rodent (9L) and human (U87) glioma
cell lines stably expressing CYP4B1, and in vivo in a subcutaneous 9L tumor model
in nude mice. The most sensitive CYP4B1-expressing glioma clone, 9L4B1-60,
displayed an LD50 of 2.5 microM for 2-AA and 4-IM after 48 h of prodrug
incubation, whereas 20 times higher prodrug concentrations did not cause any
significant toxicity to control cells. Substantial killing of control tumor cells
by 2-AA was achieved by co-culturing these cells with CYP4B1-expressing cells at
a ratio of 100:1, and toxic metabolites could be transferred through medium. In
both CYP4B1-expressing cells and co-cultured control cells, prodrug bioactivation
was associated with DNA fragmentation, as assayed by fluorescent TUNEL assays and
by annexin V staining. Alkaline elution of cellular DNA after exposure to 4-IM
revealed extensive protein-DNA crosslinking with single-strand breakage. Growth
of 9L-4B1 tumors in nude mice was inhibited by intraperitoneal injection of 4-IM
with minimal side effects. Potential advantages of the CYP4B1 gene therapy
paradigm include: the low concentrations of prodrug needed to kill sensitized
tumor cells; low prodrug conversion by human isozymes, thus reducing toxicity to
normal cells; a tumor-killing bystander effect that can occur even without cell
to-cell contact; and the utilization of lipophilic prodrugs that can penetrate
the blood-brain barrier.
PMID- 9650612
TI - Suppression of immunological response against a transgene product delivered from
microencapsulated cells.
AB - A potential obstacle to successful gene therapy for some patients is the in vivo
production of neutralizing antibodies against the recombinant therapeutic product
delivered. To mimic this clinical situation, we implanted microencapsulated
recombinant cells producing human growth hormone into C57B1/6 mice to provoke
antihuman growth hormone antibody production. We then investigated the efficacy
of different immunosuppressive treatments to inhibit the development of
neutralizing antibodies. The experimental mice were treated with either an
immunosuppressive drug (FK506 or cyclophosphamide), a cytokine (interferon-gamma
[IFN-gamma] or interleukin-12 [IL-12], or a monoclonal antibody (anti-CD4, anti
gp39, or CTLA4-Ig). Serum human growth hormone and mouse anti-human growth
hormone antibody levels were measured by enzyme-linked immunosorbent assay
(ELISA) for 4 weeks. There were three patterns of response noted among the seven
treatment groups. First, the mice receiving IFN-gamma, IL-12, anti-gp39, or CTLA4
Ig were similar to the untreated controls-no suppression of anti-hGH antibodies
and no improvement in delivery of hGH. Next, the mice receiving FK506 or
cyclosphosphamide showed > or = 90% suppression of antibodies but also no
improvement in product delivery. Last, the mice receiving anti-CD4 showed almost
complete antibody suppression over 1 month postimplantation. Furthermore, only
anti-CD4 permitted a sustained level of human growth hormone delivery to day 28,
in contrast to the controls whose human growth hormone delivery was undetectable
by day 14 postimplantation. Hence, the use of anti-CD4 inhibited formation of
neutralizing antibodies against a recombinant gene product delivered in vivo, and
allowed prolonged delivery of a foreign protein. Its role as adjunct treatment
for appropriate patients receiving gene therapy should be examined further.
PMID- 9650613
TI - Preclinical characterization of an anti-tat ribozyme for therapeutic application.
AB - A hammerhead ribozyme retroviral construct, denoted RRz2, targeting the coding
region of the human immunodeficiency virus type 1 (HIV-1) tat gene, has shown
itself to be effective in a range of test systems. Inhibition of the replication
of HIV-1 IIIB and primary drug-resistant strains in pooled transduced CEMT4 cells
was consistently found to be more than 80% compared with the control-vector
transduced cells, whereas a mutant RRz2 gave approximately 45% inhibition. A
multiple HIV-1 passage assay showed the absence of emergence of mutations within
the specific viral RNA ribozyme target sequences. This lack of generation of
ribozyme "escape mutants" occurred despite the almost complete disappearance of a
HIV-1 quasi-species in the testing virus. When RRz2 was tested in peripheral
blood lymphocytes (PBLs) from HIV-1-infected patients, paired analysis showed
that cell viability in the ribozyme-transduced HIV-1-infected PBLs was
significantly higher than that in the vector-transduced cells. This difference in
viability (vector versus RRz2) was not observed in PBLs from non-HIV-1-infected
donors. Taken together, these results indicate that the transfer of an anti-HIV-1
ribozyme gene into human T lymphocytes could have major impact on viral
replication and T cell viability in the HIV-1-infected individual.
PMID- 9650614
TI - Retrovirus-mediated in vivo gene transfer in the replicating liver using
recombinant hepatocyte growth factor without liver injury or partial hepatectomy.
AB - Retrovirus-mediated gene delivery into hepatocytes in vivo provides long-term
gene expression, which is of great importance for treating most genetic and
metabolic disorders. However, clinical application has not been realized because
of the requirement for prior 70% partial hepatectomy or chemical (toxic) liver
injury to initiate hepatocyte replication at the time of retroviral gene
transduction. In this paper, we describe a novel gene delivery system that uses
recombinant hepatocyte growth factor (rHGF) prior to retrovirus-mediated in vivo
gene transfer in the liver without partial hepatectomy or liver injury. A single
retroviral infusion through the portal vein following five systemic injections
(via the tail vein) of 100 microg/kg rHGF resulted in a 10.4% 5-bromo-2'
deoxyuridine (BrdU) labeling index (BLI) and 0.14% retroviral gene transduction
efficiency (RGTE) in hepatocytes, which were 6.3- and 12.9-fold higher than those
of controls, respectively. Modest additional increases in BLI and RGTE (13.4% and
0.22%, respectively) were seen after five systemic injections of 500 microg/kg
rHGF. The correlation between BLI and RGTE was statistically confirmed regardless
of treatment. When rats received multiple retroviral infusions through a
cannulated portal vein following five portal injections of 100 microg/kg rHGF,
RGTE was dramatically increased (1.3%) and in some areas of the liver exceeded
more than 10%. There was no evidence of liver injury in any animal. This approach
has great potential for clinical application in terms of avoiding invasive
procedures or liver injury.
PMID- 9650615
TI - Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed
neuroblastoma.
AB - Tumor cells that have been genetically modified to express immunostimulatory
genes will induce effective antitumor responses in a range of syngeneic animal
models. For human applications, transduced autologous tumor cell lines are often
difficult or impossible to prepare, so that there are strong incentives for
substituting a standardized allogeneic tumor cell line. However, such lines may
be inferior immunogens if they differ from host tumors in the antigens they
express. We have evaluated the safety, immunostimulatory, and antitumor activity
of an interleukin-2-secreting allogeneic neuroblastoma cell line in 12 children
with relapsed stage IV neuroblastoma. They received two to four subcutaneous
injections of cells in a dose-escalating schedule, up to a maximum of 10(8) cells
per injection. There was induration and pruritus at the injection site, and skin
biopsies revealed mild panniculitis with CD3+ cells surrounding scanty residual
tumor cells. There was a limited but significant peripheral monocytosis. No
patient showed any increase in direct cytotoxic effector function against the
immunizing cell line, but 3 patients had a rise in the frequency of neuroblastoma
reactive cytotoxic T lymphocyte precursor cells. One child had > 90% tumor
response (PR), 7 had stable disease, and 4 had progressive disease in response to
vaccine alone. Although these results offer some encouragement for the continued
pursuit of allogeneic vaccine strategies in human cancer, the antitumor immune
responses we observed are inferior to those obtained in an earlier immunization
study using autologous neuroblastoma cells. Hence, we suggest that this earlier
approach remains preferable, its difficulties notwithstanding.
PMID- 9650616
TI - Adenovirus-mediated transduction of intestinal cells in vivo.
AB - The intestinal tract has many features that make it an attractive target for
therapeutic gene transfer. In this study, replication-defective adenoviral
vectors were used to explore parameters that may be important in administering
gene therapy vectors to the intestine. After surgically accessing the intestine,
an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was
directly injected into various regions of the small and large intestine of rats
and rabbits. Significant transduction of the tissue was observed and
histochemical staining was used to identify enterocytes as the primary targets of
gene transfer. Expression of beta-Gal did not differ substantially when the virus
was administered to the duodenum, ileum, or colon. When the vector was directly
administered to segments of the distal ileum containing a Peyer's patch,
transgene expression was approximately 10-fold higher than in segments lacking a
Peyer's patch. In the Peyer's patches, a high level of expression was localized
to epithelial cells, potentially M cells, overlying the lymphoid follicle domes.
Transduction of these cells could have application in DNA-mediated oral
vaccination. Administration of an adenoviral vector encoding a secreted alkaline
phosphatase to the lumen resulted in expression and secretion of this gene
product into the circulation. This finding demonstrates the potential of
enterocytes to serve as heterotopic sites for the synthesis of heterologous gene
products that would be secreted into the lumen of the intestinal tract or into
the bloodstream.
PMID- 9650617
TI - A novel three-pronged approach to kill cancer cells selectively: concomitant
viral, double suicide gene, and radiotherapy.
AB - Two obstacles limiting the efficacy of nearly all cancer gene therapy trials are
low gene transduction efficiencies and the lack of tumor specificity. Recently, a
replication-competent, E1B-attenuated adenovirus (ONYX-015) was developed that
could overcome these limitations, because it was capable of efficiently and
selectively destroying tumor cells lacking functional p53. In an attempt to
improve both the efficacy and safety of this approach, we constructed a similar
adenovirus (FGR) containing a cytosine deaminase (CD)/herpes simplex virus type-1
thymidine kinase (HSV-1 TK) fusion gene, thereby allowing for the utilization of
double-suicide gene therapy, which has previously been demonstrated to produce
significant antitumor effects and potentiate the therapeutic effects of
radiation. The FGR virus exhibited the same tumor cell specificity and
replication kinetics as the ONYX-015 virus in vitro. Importantly, both the CD/5
FC and HSV-1 TK/GCV suicide gene systems markedly enhanced the tumor cell
specific cytopathic effect of the virus, and, as expected, sensitized tumor cells
to radiation. By contrast, neither the FGR virus nor either suicide gene system
showed significant toxicity to normal human cells. Both suicide gene systems
could be used to suppress viral replication effectively, thereby providing a
means to control viral spread. The results support the thesis that the three
pronged approach of viral therapy, suicide gene therapy, and radiotherapy may
represent a powerful and safe means of selectively destroying tumor cells in
vivo.
PMID- 9650618
TI - Human melanoma cells transfected with the B7-2 co-stimulatory molecule induce
tumor-specific CD8+ cytotoxic T lymphocytes in vitro.
AB - Neoplastic cells express tumor-associated antigens, but tumor rejection seldom
occurs in vivo. The absence of an effective immune response may be explained by
the inability of tumor cells to deliver co-stimulatory signals. Indeed,
transfection of either B7-1 or B7-2 co-stimulatory molecules into mouse tumor
cells enhances antitumor immune responses. In this study, we stably transfected
human melanoma cells with the cDNA encoding the B7-2 molecule to evaluate in
vitro: (i) the induction of anti-melanoma cytotoxic T lymphocytes (CTL) by
stimulation of CD8+ T cells, purified from healthy donors and a melanoma patient,
with B7-2 transfected allogeneic HLA-matched melanoma cells; (ii) the tumor
specificity and the HLA restriction of the induced CTL; and (iii) the feasibility
to propagate long-term antimelanoma CTL lines. We found that B7-2 transfected,
but not untransfected or mock-transfected, melanoma cells activated MHC-class I
restricted, melanoma-specific CD8+ CTL from healthy donors. More importantly,
CD8+ tumor-associated lymphocytes, purified from a tumor-invaded lymph node of a
melanoma patient and stimulated with B7-2-transfected melanoma cells, acquired a
strong reactivity toward the autologous tumor. CTL lines with specific cytolytic
activity could be propagated in long-term culture. These results indicate that:
(i) the expression of the B7-2 molecule into human melanoma cells makes them
immunogenic and able to act as antigen-presenting cells and (ii) purified CD8+
cells, stimulated with B7-2+ allogeneic HLA-matched melanoma cells,
preferentially recognize melanoma-specific rather than allogeneic antigens. This
study may have clinical implications for passive and/or active immunotherapy in
melanoma patients.
PMID- 9650619
TI - Retroviral vector-mediated expression in primary human T cells of an endoplasmic
reticulum-retained CD4 chimera inhibits human immunodeficiency virus type-1
replication.
AB - Intracellular expression of genes that inhibit key steps in the human
immunodeficiency virus (HIV-1) replicative cycle could offer an alternative
therapy for AIDS treatment. One of these approaches involves the inhibition of
env protein maturation through the expression of CD4 molecules with added
exogenous sequences that promote their retention in the endoplasmic reticulum
(ER). We have tested this strategy using a CD4 chimera (CD4epsilon10) containing
an ER retention sequence derived from the TCR CD3-epsilon chain. Transfection of
CD4epsilon10 in the human T cell line Jurkat made it resistant to infection with
two different HIV-1 isolates, which was evaluated by measuring p24 antigen
production, induction of apoptosis, and syncytia formation. Furthermore,
polymerase chain reaction (PCR) analysis of genomic DNA showed no traces of the
proviral HIV-1 genome in CD4epsilon10-transfected cells, suggesting it was not
maintained latently in these cells. To facilitate the delivery of the
CD4epsilon10 chimera to primary cells from AIDS patients, a Moloney-based
retroviral vector was constructed that expresses CD4epsilon10 under the
transcriptional control of the HIV-1 long terminal repeat (LTR) promoter.
Transduction of the MT-2 human T cell line with this vector rendered it resistant
to infection with HIV-1 by a process that involved the inhibition of gp160
proteolytic processing. Finally, transduction of the CD4epsilon10 chimera into T
lymphoblasts derived from asymptomatic HIV-infected individuals demonstrated a
protective effect, resulting in both an increased cellular proliferation rate and
an increased percentage of CD4+ cells. These results suggest that it is feasible
to use retroviral transduction of CD4epsilon10 as a gene therapy approach for
AIDS treatment.
PMID- 9650620
TI - Corrective transduction of human epidermal stem cells in laminin-5-dependent
junctional epidermolysis bullosa.
AB - Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2,
which are encoded by three different genes, LAMA3, LAMB3, and LAMC2,
respectively. We have isolated epidermal keratinocytes from a patient presenting
with a lethal form of junctional epidermolysis bullosa characterized by a
homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3
polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin
5 and to assemble hemidesmosomes, maintained the impairment of their adhesive
properties, and displayed a decrease of their colony-forming ability. A
retroviral construct expressing a human beta3 cDNA was used to transduce primary
beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced
with an efficiency of 100%. Beta3-transduced keratinocytes were able to
synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully
restored the keratinocyte adhesion machinery, including the capacity of proper
hemidesmosomal assembly, and prevented the loss of the colony-forming ability,
suggesting a direct link between adhesion to laminin-5 and keratinocyte
proliferative capacity. Clonal analysis demonstrated that holoclones expressed
the transgene permanently, suggesting stable correction of epidermal stem cells.
Because cultured keratinocytes are used routinely to make autologous grafts for
patients suffering from large skin or mucosal defects, the full phenotypic
reversion of primary human epidermal stem cells defective for a structural
protein opens new perspectives in the long-term treatment of genodermatoses.
PMID- 9650621
TI - Human immunodeficiency virus type 2 lentivirus vectors for gene transfer:
expression and potential for helper virus-free packaging.
AB - In addition to the long-term expression of the transgene provided by all
retroviral vectors, lentiviruses present the opportunity to transduce nondividing
cells and potentially achieve regulated expression. The development of lentiviral
vectors requires the design of transfer vectors to ferry the transgene with
efficient encapsidation of the transgene RNA and with full expression capability,
and of a packaging vector to provide packaging machinery in trans but without
helper virus production. For both vectors, a knowledge of packaging signal is
required-the signal to be included in the transfer vector but excluded from the
packaging vector. Among the human lentiviruses, human immunodeficiency virus type
1 and type 2 (HIV-1 and HIV-2), we think HIV-2 is better suited for gene transfer
than HIV-1. It is less pathogenic and thus safer during design and production;
its desirable nuclear import and undesirable cell-cycle arrest functions are
segregated on two separate genes. In HIV-1 infection, it is less likely to
recombine with the resident HIV-1, and it may itself downregulate HIV-1
expression. Evidently, elements located both upstream and downstream of the
splice donor site in the leader sequence participated in RNA encapsidation and
these sequences appeared necessary and sufficient. Deletion of both sequence
elements resulted in a dramatic curtailment of RNA encapsidation and helper virus
production. This was accompanied by some but acceptable loss of gene expression
capability. The helper virus-free phenotype and expression capability of the
double mutant was maintained upon replacement of its 3' long terminal repeat with
a minigene cassette containing a transcriptional termination signal and a drug
resistance marker gene. Deletion of the splice donor site itself had a dramatic
negative effect on gene expression, supporting the important role of this element
in the life of RNA.
PMID- 9650622
TI - Redox gene therapy protects human IB-3 lung epithelial cells against ionizing
radiation-induced apoptosis.
AB - Toxicity to nontumor-derived tissue has proven to be a significant obstacle in
achieving therapeutic levels of gamma irradiation in the treatment of cancer. The
formation of reactive oxygen species (ROS) such as superoxide radicals (O2-)
following irradiation is thought to be a major determinant of cellular damage. To
this end, we describe the generation of two recombinant adenoviral vectors
expressing the radical-scavenging enzymes MnSOD and CuZnSOD to test therapeutic
strategies of radioprotection. Using a human lung epithelial cell line (IB-3), we
have demonstrated that infections with both Ad.CMVMnSOD or Ad.CMVCuZnSOD
significantly increase both the levels of SOD protein and enzymatic activity as
compared to control cells. This increase in SOD expression reduced the level of
apoptosis at 72 hr post-irradiation by 50% as compared to mock- or Ad.CMVLacZ
infected cells. Such studies provide the foundation for radioprotective gene
therapies in the treatment of cancer.
PMID- 9650623
TI - Effects of reward and response cost on response inhibition in AD/HD, disruptive,
anxious, and normal children.
AB - In previous research, children with attention deficit/hyperactivity disorder
(AD/HD) have demonstrated impaired response inhibition on the stop paradigm. In
this study we examined whether this impairment in fact reflects a motivational
deficit. Four groups of children (age range 7-13 years) participated in the
study: 14 AD/HD children, 21 normal controls, 14 disruptive children, and 14
anxious children. The psychopathological groups were recruited from special
educational services and mental health outpatient clinics. Parent, teacher, and
child questionnaires were used to select children with pervasive disorders.
Normal controls attended regular classes and scored low on all questionnaires.
Children were tested once with reward contingencies and once with response cost
contingencies in a randomized cross-over design. We hypothesized that if a
motivational deficit underlies poor response inhibition in AD/HD children, this
deficit will be remedied by response contingencies. Despite the presence of
response contingencies, AD/HD children showed poor response inhibition compared
with normal controls. Findings argue against a motivational explanation for the
response inhibition deficit in AD/HD children.
PMID- 9650624
TI - Social anxiety in children with anxiety disorders: relation with social and
emotional functioning.
AB - Investigated the psychometric properties of the Social Anxiety Scale for children
Revised (SASC-R) as well as relations between social anxiety and children's
social and emotional functioning. Participants were a clinic sample of children,
ages 6-11 with anxiety disorders (N = 154) who completed the SASC-R. For a subset
of these children, parent ratings of social skills, and self-ratings of perceived
competence and peer interactions were also obtained. Factor analysis of the SASC
R supported the original three-factor solution and internal consistencies were in
the acceptable range. Among children with simple phobia, scores on the SASC-R
differentiated those with and without a comorbid social-based anxiety disorder.
Social anxiety was also associated with impairments in social and emotional
functioning. Specifically, highly socially anxious children reported low levels
of social acceptance and global self-esteem and more negative peer interactions.
Girls with high levels of social anxiety were also rated by parents as having
poor social skills, particularly in the areas of assertive and responsible social
behavior.
PMID- 9650625
TI - Assessing culturally different students for attention deficit hyperactivity
disorder using behavior rating scales.
AB - Behavior rating scales are commonly used in the assessment of attention deficit
hyperactivity disorder (ADHD). However, there is little information available
concerning the extent to which scales are valid with culturally different
students. This study explored the use of the ADHD-IV Rating Scale School Version
with male Caucasian (CA) and African American (AA) students from ages 5 to 18
years. Teachers rated AA students higher on all symptoms across all age groups.
LISREL analysis indicated that scale does not perform identically across groups.
This was supported by the results of multidimensional scaling with suggested that
there is a different relation between items across groups. Implications for
research and practice are discussed.
PMID- 9650626
TI - Moderators and mediators of the effects of interparental conflict on children's
adjustment.
AB - Moderational and mediational models of the relationships among appraisals,
interparental conflict, and children's adjustment were tested in a sample of 174
families with a school-age child. Parents rated children's exposure to
interparental conflict and internalizing, externalizing, and total behavior
problems. Children completed questionnaires regarding their appraisals of their
parents' conflicts, including frequency and intensity, perceived threat, control,
and self-blame, as well as measures of anxiety and depression. Results overall
demonstrated more consistent support for the moderational than mediational
hypotheses. Appraisals of conflict properties, threat, self-blame, and perceived
control moderated the effects of interparental conflict on externalizing, total
problems, and anxiety in boys. Conflict properties, threat, self-blame, perceived
control, and self-calming acted as moderators of internalizing in girls.
PMID- 9650627
TI - Cross-informant agreement in the assessment of social phobia in youth.
AB - In the present study involving children and adolescents with a principal
diagnosis of social phobia, we measured parent-child agreement regarding social
anxiety symptoms. Additionally, we examined variables related to the severity of
the children's social phobia symptoms as reported by children and as rated by
clinicians. Examination of cross-informant agreement indicated little difference
between mean parent and children ratings of the children's social fears. In
contrast, there was a significant difference in parent and children ratings of
the children's avoidance, with parents endorsing greater degrees of social
avoidance. Children's report of social avoidance was negatively related to scores
on a measure of self-presentational concerns (i.e., social desirability).
Clinicians' determination of the severity of the children's social phobia was
also influenced by the children's self-presentation as well as parent report of
social avoidance and children's depression scores. Thus, this differential
weighting by the clinician of parent versus child report may be related to the
finding that children's self-reported social avoidance was negatively related to
their concerns regarding positive self-presentation. Results suggest the need to
consider the impact of social desirability when examining clinical
characteristics of children and adolescents with social phobia.
PMID- 9650629
TI - Alcohol drinking and blood pressure among adolescents.
AB - The purpose of this study was to evaluate alcohol consumption among adolescents
from Tucuman, Argentina, and to determine its possible relationship with
increased levels of blood pressure. Three hundred fifty-six students aged 13-18
included in the study were asked to answer questionnaires anonymously. Two blood
pressures measures were then taken. Differences between both sexes were found in
quantity and frequency of alcohol consumption. Enjoyment was determined to be the
main reason for drinking. There was an association between frequency and alcohol
related problems, and smoking habits. There were also differences in blood
pressure among males and females. A weak, but significant, relationship between
quantity/frequency index and diastolic blood pressure was found. A greater
prevalence of hypertension in male heavy drinkers was noted as well. Because this
addiction implies multiple social problems and it also accounts for a
hypertension risk factor, the importance of aiming at developing prevention
strategies for alcohol abuse among adolescents is stressed.
PMID- 9650628
TI - Comorbidity of conduct and depressive problems at sixth grade: substance use
outcomes across adolescence.
AB - The comorbidity of conduct and depressive problems and substance use outcomes
were examined in a community-based sample of 340 African American males and
females. Alcohol, tobacco, and marijuana use were examined at Grades 6, 8, and 10
based on the following group membership at sixth grade: (a) comorbid conduct and
depressive problems; (b) conduct problems only; (c) depressive problems only; (d)
neither conduct nor depressive problems. Overall, the two conduct problem groups
displayed the highest levels of substance use, although at some time points,
comorbid youth displayed significant higher substance use levels. Subjects with
depressive problems only displayed levels of substance use that were equivalent
to subjects in the nonproblem group. Results highlight the importance of
controlling for comorbid symptoms, possible interactive effects between conduct
and depressive problems, and implications for treatment and prevention of
substance use.
PMID- 9650630
TI - Relative and combined effects of ethanol and protein deficiency on zinc, iron,
copper, and manganese contents in different organs and urinary and fecal
excretion.
AB - The relative contribution of protein deficiency to the altered metabolism of
certain trace elements in chronic alcoholics is not well defined, so this study
was performed to analyse the relative and combined effects of ethanol and protein
deficiency on liver, bone, muscle, and blood cell content of copper, zinc, iron,
and manganese, and also on serum levels and urinary and fecal excretion of these
elements in four groups of eight animals each that were pair-fed during 8 weeks
with a nutritionally adequate diet, a 36% (as energy) ethanol-containing
isocaloric diet, a 2% protein isocaloric diet, and a 36% ethanol 2% protein
isocaloric diet, respectively, following the Lieber-DeCarli model. Five
additional rats were fed ad lib the control diet. Protein malnutrition, but not
ethanol, leads to liver zinc depletion. Both ethanol and protein malnutrition
cause muscle zinc depletion and increase urinary zinc and manganese excretion,
whereas ethanol also increases urinary iron excretion and liver manganese
content. No differences were observed regarding copper metabolism.
PMID- 9650631
TI - Altered ambient temperature and ethanol-induced conditioned place preference in
mice.
AB - Previous studies with rats exposed to altered ambient temperature (Ta) or with
mice selectively bred for their thermal response to ethanol have shown that a
reduced hypothermic response is correlated with decreased place aversion and
greater place preference, respectively. The present experiment was designed to
test whether alterations in Ta would alter ethanol's ability to produce
conditioned place preference in genetically heterogeneous mice. Three groups of
mice underwent a differential conditioning procedure that paired one distinctive
floor texture with ethanol (2.25 g/kg, i.p.) and a different floor texture with
saline. During conditioning, each group was exposed to a different Ta: cold (10
degrees C), normal (21 degrees C), or warm (34 degrees C). Each group was further
divided and subgroups were tested for preference at either the conditioning
temperature or a different temperature. Consistent with previous findings, mice
conditioned and tested at normal Ta developed a conditioned preference for the
ethanol-paired floor. In contrast, mice exposed to a warm or cold Ta during
conditioning or testing failed to show place conditioning. Although exposure to
either warm or cold Ta interfered with place conditioning, only the warm Ta had
an effect on hypothermia. These findings suggest that altered Ta produced stimuli
that may have interfered with the association between floor cues and ethanol
during conditioning or interfered with expression of this association during
testing.
PMID- 9650632
TI - Splenic sympathetic response to endotoxin is blunted in the fetal alcohol-exposed
rat: role of nitric oxide.
AB - This study was designed to test the hypothesis that nitric oxide (NO) mediates
the blunted splenic sympathetic response to lipopolysaccharide (endotoxin) that
occurs in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day
old rats, were progeny of pregnant dams fed an alcohol diet (35% of the calories
were derived from ethanol) or their control and pair-fed (PFC) cohorts. We
examined the effects of lipopolysaccharide (LPS) (0.5 mg/kg, i.p.) on splenic
norepinephrine (NE) turnover, an index of sympathetic neural activity, splenic
inducible NO synthase (iNOS) protein immunoreactivity, and NO metabolites
nitrite/nitrate concentrations in plasma. In response to LPS, splenic NE turnover
was increased by more than twofold in the PFC groups, but the increase did not
occur in their FAE cohorts. The blockade of NOS with L-NAME (30 mg/kg, i.p.)
reversed this difference. In both the PFC and FAE rats, basal levels of splenic
iNOS protein immunoreactivity were equally barely detected and plasma NO
metabolite levels were relatively low (25 microM in both groups). In response to
LPS, however, iNOS protein displayed a marked increase in the PFC group and an
even greater increase (by close to threefold) in the FAE rats. LPS also
substantially increased plasma NO metabolite levels by close to eightfold in the
control groups, but by 15-fold in their FAE cohorts compared to the basal levels.
These findings support the hypothesis that in the FAE rat, an augmented NO
formation accounts for the blunted sympathetic response to endotoxin.
PMID- 9650633
TI - Pyrrolidine dithiocarbamate attenuates alcohol-induced leukocyte-endothelial cell
interaction and cerebral vascular damage in rats: possible role of activation of
transcription factor NF-kappaB in alcohol brain pathology.
AB - Effects of chronic (14-day) pretreatment of orally administered pyrrolidine
dithiocarbamate (PDTC) (100 or 200 mg/kg/day) on alcohol-induced venular
cerebrovasospasm, microvessel rupture, leukocyte-endothelial chemoattraction, and
microhemorrhaging was studied by direct, quantitative in vivo high-resolution TV
microscopy of the intact rat brain. Sham animals chronically treated with placebo
exhibited concentration-dependent venular cerebrovasospasm, endothelial-leukocyte
rolling and attraction, microvessel rupture. and focal hemorrhages, irrespective
of route (i.e., perivascular, systemic) of ethanol administration. PDTC
pretreatment either prevented or ameliorated greatly the cerebrovasospasm,
leukocyte-endothelial chemoattraction, and brain vascular damage induced by
ethanol. These new data suggest that alcohol induces cerebral vascular and brain
damage by reperfusion injury events, which trigger induction of proinflammatory
factors, and transcription factor NF-kappaB and lipid peroxidation of vascular
smooth muscle and endothelial cell membranes; these proinflammatory, pro-oxidant,
and redox events could play a crucial role in the pathogenesis of alcohol-induced
cerebral ischemia and stroke.
PMID- 9650634
TI - The D2 dopamine receptor gene: a review of association studies in alcoholism and
phenotypes.
AB - The role of the D2 dopamine receptor (DRD2) gene in alcoholism and other
substance use disorders has come under intense investigation since the minor TaqI
A (A1) allele of the DRD2 gene was first reported to be associated with
alcoholism. In a meta-analysis of 15 US and international studies of European
(non-Hispanic) Caucasians, consisting of 1015 alcoholics (more severe and less
severe) and 898 controls (unassessed and assessed for alcoholism), alcoholics had
a higher prevalence (p < 10(-7)) and frequency (p < 10(-5)) of the A1 allele than
controls. The prevalence of the A1 allele was 1.5-fold higher in more severe than
less severe alcoholics (p < 10(-4)), whereas unassessed controls had a twofold
higher prevalence of the A1 allele than assessed controls (p < 10(-4)). Whereas
more severe alcoholics had a threefold higher A1 allelic prevalence than assessed
controls (p < 10(-10)), A1 allelic prevalence was virtually identical in less
severe alcoholics and in unassessed controls. The A1 allele has also been
associated with other drug problems including cocaine, nicotine, and
polysubstance abuse. Furthermore, the minor TaqI B (B1) allele of the DRD2 gene
has been associated with alcoholism and psychostimulant (cocaine, amphetamine)
abuse. Beyond association studies, phenotypic differences exist between genotypes
containing the TaqI A minor (A1A1 and A1A2) and major (A2A2) alleles of the DRD2.
These different phenotypes have been identified through a number of approaches,
including pharmacological, neurophysiological, neuropsychological, stress,
personality, metabolic, and treatment studies. In conclusion, the present review
suggests that the type of alcoholics and the nature of controls used are among
critical factors in DRD2 association studies in alcoholism. Intronic mutations in
both the 3'(TaqI A) and 5'(TaqI B) regions of the DRD2 associate with alcoholism
and other drug use disorders. The identification of phenotypes of DRD2 genotypes
suggests that the observed intronic DRD2 mutations may have functional
consequences that predispose individuals to a variety of substance use disorders.
PMID- 9650635
TI - A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and
substance abuse.
AB - Association studies with the DRD2 Taq1A marker have been variable in implicating
DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse.
Given that the Taq1A marker is not functionally significant, second-generation
studies on the DRD2 receptor to identify functional variants and evaluate their
effect on the phenotype are the logical step towards confirming and extending the
DRD2 hypothesis. This article discusses the implications and process of progress
made in these directions. The new findings are the description of structural
variants in the D2 receptor, the demonstration that one of these, Ser311Cys,
largely prevents signal transduction following receptor activation and the use of
Ser311Cys in a large association and sib-pair linkage anlysis in an American
Indian isolate. In this particular population, the Cys311 variant is far more
abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2
intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and
15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism,
substance use disorders, or schizophrenia. The implication is that a DRD2 variant
that dramatically impairs receptor function was not sufficient to significantly
alter alcoholism vulnerability in a relatively large and also genetically and
environmentally homogeneous sample.
PMID- 9650636
TI - Alternative strategies for uncovering genes contributing to alcoholism risk:
unpredictable findings in a genetic wonderland.
AB - In spite of technological advances in genetic mapping, the field of alcoholism
genetics has had few findings that could be confirmed. Possible sources for the
largely negative results and suggested ways for improving the search for genes
contributing to alcoholism risk are discussed. These include the choice of
phenotype to be studied, whether narrow or broad, whether only mild or severe
forms are included, and whether or not comorbidity should be excluded. The
ascertainment schema for selecting families utilized in our laboratory which
results in an especially high recurrence risk will be discussed with respect to
finding candidate genes. The complexity of the alcoholism phenotype will be
discussed with respect to the existence of phenocopies, genetic heterogeneity,
and the difficulties associated with defining the disorder in a way that covers
all ages and both genders adequately. Finally, the equivocal results found for
the D2 dopamine receptor are discussed with respect to current data analytic
techniques, which emphasize affected sib-pairs, techniques that may be especially
problematic for a disorder such as alcoholism that has marked tendencies for
phenocopies to arise.
PMID- 9650637
TI - Why different rules are required for polygenic inheritance: lessons from studies
of the DRD2 gene.
AB - In 1990 Blum, Noble and coworkers reported a significant association between the
1 allele of the Tarq1A polymorphism of the D2 dopamine receptor gene (DRD2) and
severe alcoholism. Subsequently, some reports using both linkage and association
techniques supported this finding whereas others either did not, or seemed not to
support this association. Although some of the controversy is due to true
variability in the frequency of the D2A1 allele in different groups of alcoholics
and controls, some is also due to the frequent attempt to apply the rules of
single-gene disorders to what is in all likelihood a multifactorial, polygenic
disorder. When the rules that are appropriate to polygenic inheritance are used a
significant portion of the controversy is resolved. Those rules, and their
application to the role of the DRD2 gene in addictive, impulsive behaviors, are
reviewed.
PMID- 9650638
TI - Issues and strategies in the genetic analysis of alcoholism and related addictive
behaviors.
AB - Research into the genetics of alcoholism susceptibility and related behaviors has
become highly contentious for a number of reasons: at issue is the identification
of factors that may ultimately determine human behaviors, the limitations of the
technologies being used to conduct relevant studies have not been assessed
exhaustively, and independent studies have produced widely different results.
Addressing these and other questions of relevance in the dissection of the
genetic basis of alcoholism susceptibility will be nothing if not difficult. In
this article, we consider issues related to one not-so-minor research angle being
used more and more in investigations of alcoholism and related disorders: the
identification of susceptibility loci through the use of anonymous (or seemingly
anonymous) DNA markers. We also consider issues that might promote (or resist)
the reconcilability of independent study results, and describe some basic
strategies that might help make study results more compelling in light of the
complexity of alcoholism and related behaviors.
PMID- 9650639
TI - Molecular genetics of alcoholism and other addiction/compulsive disorders.
General discussion.
PMID- 9650640
TI - Cadmium and calcium-dependent c-fos expression in mesangial cells.
AB - Cadmium is a carcinogenic metal known to increase the expression of several
protooncogenes in a variety of cells. although the underlying mechanisms are
unknown. Renal mesangial cells are smooth muscle cells in which Ca2+ signaling
pathways regulate the induction of c-fos through both cAMP-dependent and mitogen
activated protein kinase- (MAPK-) dependent pathways. We report that c-fos is
induced in these cells by both protein kinase C- (PKC-) dependent (phorbol ester,
platelet-derived growth factor), and independent (serum, ionomycin) mechanisms.
In all cases, prevention of an increase in cytosolic [Ca2+] with the chelator
BAPTA prevented this induction. CdCl2 (10 microM) caused an accumulation of c-fos
mRNA over 30 min that was sustained for at least 8 h. Cycloheximide inhibits
turnover of c-fos mRNA and shows a synergistic effect with Cd2+ on transcript
levels. Together with a similar half life of the transcript whether accumulated
in response Cd2+ or induced by phorbol ester, this suggests induction of c-fos by
Cd2+ rather than an effect of Cd2+ on transcript stability. Cadmium increased
MAPK activity by 5 min; this was sustained for at least 8 h, consistent with the
time course of c-fos mRNA accumulation. The MAPK kinase inhibitor PD98059 caused
a marked decrease in the induction of c-fos by Cd2+, but did not eliminate the
phenomenon completely. Although Cd2+ has been reported to activate PKC in vitro,
no effect was found on PKC activity in Cd2+ -treated cells, indicating the
activation of MAPK by Cd2+ is through an unidentified PKC-independent pathway. We
conclude that Cd2+ can cause a sustained induction of c-fos in part through
sustained activation of MAPK, that contrasts with the transient activation of
these species in response to physiological mitogenic stimuli.
PMID- 9650641
TI - Effect of calmodulin-inhibitors and verapamil on the nephrotoxicity of cadmium in
rat.
AB - Recent reports indicate that calmodulin inhibitors (CIs) can modify cadmium (Cd)
toxicity in rodents. Pretreatment with CIs prevents Cd-induced testicular damage
in mice and reduces the severity of such damage in rats. On the other hand it has
been suggested that the cellular transport of Cd can be partly inhibited by the
calcium-channel inhibitor, verapamil. The aim of this study was to determine
whether these inhibitors can prevent the toxic effects of Cd on the kidney which
is the critical organ. For that purpose, we have examined the effects of two CIs
(trifluoperazine and chlorpromazine) and of verapamil on the development of
tubular damage in female Sprague-Dawley rats. The animals were injected
subcutaneously 5 days a week for 8 weeks with cadmium chloride (1 mg Cd/kg),
alone or in association with trifluoperazine (20 mg/kg), chlorpromazine (15
mg/kg) or verapamil (2 x 5 mg/kg). The development of renal dysfunction was
followed by measuring the urinary excretion of the low molecular weight protein
Clara cell protein (CC16). In Cd-treated rats, the urinary excretion of CC16
started to increase from week 6 to reach at the end of experiment values more
than 100-times above normal. CIs or verapamil did not influence the rise of
urinary CC16 induced by Cd. The three inhibitors, by contrast, enhanced the
accumulation of Cd in the liver and, at the exception of chlorpromazine, in the
kidneys of Cd-treated rats. Although interfering with the metabolism of Cd, CIs
and verapamil do not prevent renal damage in rats chronically exposed to this
heavy metal.
PMID- 9650642
TI - Effect of cocaine, 95% oxygen and ellagic acid on the development and antioxidant
status of cultured rat embryos.
AB - Prenatal exposure to cocaine has been associated with adverse developmental
effects and current data suggest cocaine induced malformations are caused by
ischemic-reperfusion injury. This study was undertaken to assess a new in vitro
model which uses a routine rat whole embryo culture system that incorporates a
change in oxygen status, and to examine the effects of altered oxygen status and
pretreatment with ellagic acid (EA), an anti-oxidant, after cocaine exposure.
Embryos were evaluated by determining a developmental score and by measuring
tissue reduced glutathione (GSH) levels. Following re-oxygenation with 95% O2 for
the last 6 h of culture, embryos treated with cocaine had reduced developmental
scores and GSH levels. Embryos treated with cocaine and not re-oxygenated with
95% O2 did not have reduced developmental scores. EA blocked the effects of
cocaine on developmental score and GSH level. These data support ischemia
reperfusion injury as the mechanism of cocaine developmental toxicity.
PMID- 9650643
TI - Hepatoprotective activity of thymoquinone in isolated rat hepatocytes.
AB - Thymoquinone, the active constituent of Nigella sativa, was tested in isolated
rat hepatocytes as a hepatoprotective agent against tert-butyl hydroperoxide
(TBHP) toxicity. TBHP (2 mM) was used to produce oxidative injury in isolated rat
hepatocytes and caused progressive depletion of intracellular glutathione (GSH),
loss of cell viability as evidenced by trypan blue uptake and leakage of
cytosolic enzymes, alanine transaminase (ALT) and aspartic transaminase (AST).
Preincubation of hepatocytes with 1 mM of either thymoquinone or silybin, which
is a known hepatoprotective agent, resulted in the protection of isolated
hepatocytes against TBHP induced toxicity evidenced by decreased leakage of ALT
and AST, and by decreased trypan blue uptake in comparison to TBHP treated
hepatocytes. Both thymoquinone and silybin prevented TBHP induced depletion of
GSH to the same extent. Although thymoquinone protected the liver enzymes
leakage, the degree of protection was less than that caused by silybin.
PMID- 9650644
TI - Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats.
AB - The hepatotoxic effect of cypermethrin and the expression of hepatic genes at the
mRNA level, as molecular markers of liver damage, were evaluated in rats
following exposure to cypermethrin. The expression of hepatic genes was compared
with conventional liver functional tests, and correlations were made by studying
the liver at the ultrastructural level. Cypermethrin treated rats presented a
significant decrease, of 79% and 22%, on the expression of albumin and apo E
genes at 5 days, respectively. The levels of apo A-1 and apo B mRNA were
increased up to four- and fivefold, respectively. This increase did not correlate
with the serum values of HDL and VLDL lipoprotein particles. Intracytoplasmic
lipid droplets were observed after the first 2 days following cypermethrin
administration, suggesting that apo A-1 and B mRNA were translated but not
secreted. There were significant correlations between the low values of the
albumin gene expression, the decrease in the HDL concentrations, and the
ultrastructural alterations, respectively. These alterations were mainly a large
amount and increased size of mitochondria in the animals exposed to cypermethrin.
It is concluded that under the experimental conditions used, cypermethrin may
alter the metabolism of lipids and proteins in rat liver.
PMID- 9650645
TI - Toxicokinetics of trimethyltin in four inbred strains of mice.
AB - Sixteen week old male AKR/J, Balb/cByJ, C57B1/6J and DBA/2J mice received single
i.p. injections of trimethyltin (TMT). The toxic effects were weight loss,
hyperexcitability, tremor, clonic-tonic convulsion, posterior paresis and death.
The minimum toxic dose was 1.8 mg/kg, for the AKR strain and 2.3 mg/kg for the
other strains. The highest non-lethal dose was 2.7 mg/kg for the AKR, DBA/2 and
C57B1/6 strains and 3.0 mg/kg for the Balb/c strain. Blood levels of TMT peaked
within 1 h and declined with half-lives of approximately 1.5 days. Blood levels
of TMT were lower in the C57B1/6 mice due to greater tissue binding of TMT in
C57B1/6 mice. Some of the toxic endpoints showed different rank orders among the
strains, leading us to conclude that more than one biological process is
responsible for the acute toxic effects of TMT in mice.
PMID- 9650646
TI - Protein oxidation biomarkers in hyperoxic lung injury in rats: effects of U
74389.
AB - Hyperoxia, used therapeutically in the treatment of respiratory insufficiencies,
can cause lung injury, probably through the actions of reactive oxygen species.
The present studies were designed to test the hypothesis that oxidation of
specific proteins would provide useful biomarkers of the onset of tissue injury,
and thereby provide clues as to the mechanisms responsible. We exposed adult male
Sprague-Dawley rats to room air or to greater than 95% O2 for 60 h and examined
proteins in pleural effusion and broncho-alveolar lavage (BAL) fluids, and in
lung tissue homogenates and subfractions. Oxidation of protein thiols was
assessed by derivatization with monobromobimane, separation by electrophoresis,
and visualization of the fluorescent thioether derivatives. Derivatization with
2,4-dinitrophenylhydrazine (DNPH), electrophoresis, and western analysis was
employed to assess a different class of oxidative modifications, frequently
termed 'protein carbonyls'. In addition, we investigated the effects of the 21
aminosteroid U-74389G, 10 mg/kg, given intraperitoneally every 12 h, on
biomarkers of protein oxidation and on manifestations of lung injury. Hyperoxia
caused lung injury evidenced by pleural effusions, increases in BAL protein
concentrations, and pulmonary edema; U-74389G attenuated the first two indices of
lung injury, but did not alter edema. Protein thiol status of the fractions
studied were not affected notably by hyperoxia, or by the aminosteroid. The
formation of DNPH-reactive sites on a limited number of proteins by hyperoxia was
observed, and some of these effects were attenuated in the animals given U
74389G. Histological examination of lung tissues showed accumulation of intra
alveolar protein exudates in hyperoxic rats, and a significant attenuation of
this effect was observed in the animals treated with U-74389G. In conclusion,
studies of shifts in protein thiol status that may be caused by hyperoxia will
require increasingly specific methods of analysis, and characterization of the
specific DNPH-reactive proteins formed in hyperoxia may provide critical insights
into the mechanisms of lung injury. Administration of U-74389G offers some degree
of protection against hyperoxia and attenuation of these biomarkers of oxidation,
but the precise mechanisms by which this protection is effected will require
additional study.
PMID- 9650647
TI - The experimental toxicology of tramadol: an overview.
AB - The experimental toxicological findings of tramadol are reviewed and discussed.
Tramadol is a centrally acting analgesic. In acute toxicity studies, LD50 values
are estimated to be around 300-350 mg/kg body weight (rat, mouse, oral
administration). After intravenous administration the LD50 values ranged from 50
to 100 mg/kg body weight. In subacute and chronic toxicity studies, clinical
signs of intoxication are mainly behavioural disorders and convulsions, beginning
at dose levels of 25 mg/kg. Clinical pathological alterations or morphological
lesions, in particular neuropathological findings were not detected. Overall, the
battery of mutagenicity studies shows no evidence of a genotoxic risk to man.
Reproductive and developmental toxicity investigations and carcinogenicity
studies were without substance-dependent findings. Toxicological and
toxicokinetical data of both enantiomers did not show biologically relevant
deviations in comparison to the data on tramadol. The toxicological
characteristic of this compound is demonstrated.
PMID- 9650648
TI - Therapeutic amnioinfusions and fetal fibronectin pattern in a case with preterm
ruptured membranes that resealed.
AB - OBJECTIVE: Determination of fetal fibronectin (fFN) levels in a patient at risk
of preterm delivery and having premature rupture of the membranes. PATIENT AND
METHODS: The present case report concerns a pregnant woman with premature rupture
of the membranes at 16 weeks of gestation who was submitted to repeated
therapeutic transabdominal amnioinfusions and had a spontaneous resolution of the
rupture at 32 weeks of gestation. RESULTS: A good pregnancy outcome was observed.
High cervicovaginal fFN levels were observed during the period of membrane
rupture with following drop of fFN levels during this period and spontaneous
reseal of the membranes. CONCLUSIONS: Active expectant management, using repeated
amnioinfusions, probably played a useful role in the therapeutic success of this
pregnancy. Further, fFN was a reliable marker of the rupture of membranes. The
possible role of fFN in the clinical management of high-risk pregnancies is
confirmed.
PMID- 9650649
TI - Prenatal diagnosis of cloacal dysgenesis sequence: differential diagnosis from
other forms of fetal obstructive uropathy.
AB - Cloacal dysgenesis sequence (CDS) is a rare cause of fetal obstructive uropathy
(FOU). The prenatal differentiation of CDS from other FOU is important because
CDS is not amenable to in utero surgical intervention in the form of
vesicoamniotic shunts. We evaluated the prenatal characteristics of 8 fetuses
with CDS, including a pair of monozygotic twins concordant for CDS, in order to
identify features that would enable differentiation from other forms of FOU.
Pathologic examination in each of the 8 fetuses confirmed characteristic features
of absent anal, genital, and urinary orifices associated with a smooth perineum
and abnormal phallic development. Associated abnormalities included dysplastic
kidneys in 6, hydroureters in 5, intraluminal colonic calcifications in 2, and
hypoplastic lungs in 5. Five of these fetuses initially presented as posterior
urethral valve syndrome. Six fetuses had megacystis, and 4 underwent
vesicocenteses to evaluate urinary electrolytes, all of which were in the 'poor
risk' category. Six fetuses were male and 2 female, contradicting earlier claims
that CDS occurs only in females. Evaluation of candidates for in utero surgical
intervention should include fetal karyotype, and CDS should be suspected in cases
of FOU in whom the karyotype reveals a male fetus and sonographic evaluation
demonstrates colonic calcifications or abnormal phallic development. Diagnostic
microendoscopy may be of benefit in such cases.
PMID- 9650650
TI - Management of a case of twin-to-twin transfusion syndrome by a combined surgical
approach.
AB - OBJECTIVE: The management of a case of severe twin-to-twin transfusion syndrome
at 24 weeks of gestation is presented, using a combined surgical and medical
approach. METHODS: Operative fetoscopy was used to coagulate placental vessels
crossing the intertwin membranes. Repeated intrauterine transfusions were used to
correct recurrent anemia in the donor twin. Selective three-dimensional placental
angiography and directed histological analysis were used to study the placenta
after delivery. RESULTS: Resolution of twin-to-twin transfusion syndrome was
obtained by coagulation of placental anastomoses, but was followed by recurrent
anemia in the donor twin. This was successfully treated by serial intrauterine
blood transfusions, and 2 healthy twins were delivered at 31 weeks of gestation.
One artery-to-vein anastomosis was demonstrated to be the only communication left
between the two circulations. CONCLUSIONS: This case illustrates the limitations
of placental surgery in twin-to-twin transfusion syndrome and highlights the need
for ultrasound and Doppler follow-up of these high-risk fetuses to indicate
further treatment. Placental anastomoses can be overlooked by macroscopic
examination and injection technique, but can be demonstrated by placental
angiography.
PMID- 9650651
TI - Outcome of 116 moderate renal pelvis dilatations at prenatal ultrasonography.
AB - To determine the incidence of urinary tract abnormalities detected in the
presence of moderate fetal renal pelvis dilatation, we followed up pre- and
postnatally 116 fetuses and children between 1985 and 1995. At prenatal
ultrasound, 50 (43%) fetuses showed regressive dilatations, 57 (49%) a stable
pattern, and 9 (8%) an evolutive pattern. In the presence of an evolutive
dilatation, urinary tract obstruction was present in 8 cases. When a stable
pattern was observed, i.e., a patent uropathy was present, surgical correction
was performed in 27 of 53 (51%) cases. Regarding the postnatal evolution of 50
prenatal regressive moderate dilatations, we observed in 12 of 50 (24%)
vesicoureteric reflux, of which 5 (10%) required surgical correction, and it is
concluded that careful and extensive follow-up is mandatory.
PMID- 9650652
TI - Surgical approach of an early mammalian embryo: the rabbit model.
AB - We describe an experimental surgical model in early rabbit embryo (12.5 days of
gestation). Twenty-one embryos were operated, of which 9 survived the first
postoperative week and 5 had normal further growth until term. As far as we can
ascertain, this is the first successful report of a surgical approach in early
mammalian embryos. We think that this model may be useful for workers involved in
the study of early congenital malformations.
PMID- 9650653
TI - Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios
sequence.
AB - OBJECTIVE: To report our experience with intentional puncture of the intervening
membrane ('septostomy') for the treatment of the twin oligohydramnios
polyhydramnios sequence (TOPS). METHODS: 12 patients were diagnosed with TOPS
based on ultrasonographic findings. A 20- to 22-gauge spinal needle was used to
puncture the membrane between the twins without any attempt at amnioreduction in
9 patients, while the procedure was combined with amnioreductions in 3 patients.
RESULTS: Gestational age was 23.1 +/- 3.3 weeks at the time of septostomy and
31.1 +/- 4.4 weeks at delivery. Rapid accumulation of fluid around the 'stuck'
fetus occurred in all cases following a single procedure. Three of the 24 fetuses
died in utero and 1 died on the fifth day of life, for a combined survival of
83.3%. In the survivors, the septostomy to delivery interval ranged between 0.6
and 13 weeks (mean +/- SD 8.3 +/- 4.8). CONCLUSION: Amniotic septostomy is a
promising new method for the management of TOPS and is associated with survival
rates that are better than, or comparable to, more invasive modalities. A
multicenter trial comparing septostomy to other modalities is warranted.
PMID- 9650654
TI - A simple method to estimate volume for fetal intravascular transfusions.
AB - We derived a constant termed the transfusion coefficient to simplify the
estimation of the fetal intravascular transfusion volume. The product of the
estimated fetal weight (g) and 0.02 (transfusion coefficient), estimates the
transfusion volume (ml) required to increase the fetal hematocrit by
approximately 10 percentage points. Our estimation was comparable to Mandelbrot's
technique and better than Plecas' method for estimating fetal transfusion
volumes. Utilizing the transfusion coefficient to estimate the intravascular
transfusion volume for an anemic fetus is simple, rapid and accurate.
PMID- 9650655
TI - Fatal sepsis due to Escherichia coli after second-trimester amniocentesis.
AB - The case of a pregnant woman (16th week) needing an amniocentesis is reported.
She rapidly developed a septic shock. Despite vaginal delivery, curettage and
antibiotherapy, the patient deteriorated with the onset of an acute respiratory
distress syndrome and a typical disseminated intravascular coagulation.
Bacteriological data showed positive blood cultures to Escherichia coli. Amniotic
liquid was positive to the same E. coli. Cultures obtained from instruments,
disinfectant solutions and gel used during the procedure were negative. On the
contrary, amniotic and fetal cultures were positive to E. coli and Clostridium
perfringens. She died 2 days later. The incidence of septic shock following
amniocentesis is very low but we report the first case of fatal sepsis and
multiorgan failure, due to E. coli and C. perfringens. The mechanisms of
infection are discussed: contamination from the instruments, systemic
dissemination of bacteria coming from an asymptomatic intra-amniotic infection,
and inoculation of the placenta with a needle passing through the bowel.
PMID- 9650656
TI - Effects of antenatal thyrotropin-releasing hormone on fetal heart rate and
breathing movements.
AB - OBJECTIVE: To determine the effect of maternally administered thyrotropin
releasing hormone (TRH) on fetal heart rate (FHR) pattern and fetal breathing
movements (FBM). METHODS: Prospective observational study of 75 pregnant women
between 26 and 34 weeks' gestation in whom pharmacological fetal lung maturation
was clinically indicated. Forty-minute recordings were made of FBM or FHR
patterns before and after drug administration. Twenty-five received TRH 400
microg as an intravenous bolus, 25 TRH 400 microg in 50 ml 0.9% saline as an
intravenous infusion, and 25 acted as controls. Recordings were processed
digitally to calculate the change in FHR (n = 45) and FBM parameters (n = 30).
The main outcome measures for FHR were number of accelerations and decelerations,
baseline rate, overall and short-term variation and duration of high and low
variability, while for FBM they were rate, breath-to-breath interval and
incidence. Results between groups were compared by analysis of variance. RESULTS:
There was no significant change in FHR, accelerations or variation in any of the
groups. Similarly, there was no change in the incidence of FBM. TRH administered
as a bolus produced a small statistically but not clinically significant increase
in breathing rate (mean delta = 35 breaths/h, p = 0.004), which was not seen in
the TRH infusion and control groups. CONCLUSIONS: Maternally administered TRH as
used to enhance fetal lung maturation has no clinically significant direct effect
on FHR or FBM patterns.
PMID- 9650657
TI - 'Dual positivity' for neural tube defects and down syndrome at maternal serum
screening: gestational outcome.
AB - OBJECTIVE: To evaluate the gestational outcome of pregnancies screen-positive for
both neural tube defects (NTD) and Down syndrome (DS) ('dual positivity').
METHODS: Among 10,667 mid-trimester women screened for DS and NTD with alpha
fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin
(hCG), delivered up to July 1996, we have selected cases with both an unexplained
AFP value > or = 2.5 multiples of median (MoM) and a DS risk > or = 1:250. All
these pregnant women were managed with amniocentesis and/or CVS, ultrasound
scans, and Doppler velocimetry. We have collected all data about the gestations
with 'dual positivity' and no obvious explanation for these findings (cases with
fetal malformations related to raised AFP). RESULTS: Twelve women (1.1:1,000)
showed unexplained 'dual positivity'. Abnormal karyotypes were found in 3
fetuses, and pregnancies were terminated: there were 2 triploidies with partial
hydatiform mola, and 1 DS. In 9 cases the fetal karyotype was normal, but a
confined placental trisomy 16 was found in 4. Of the 9 continuing gestations, 8
displayed fetal growth retardation (FGR). One gestation ended with fetal death at
27 weeks. All 9 fetuses were morphologically normal, and 8 were small for
gestational age. CONCLUSIONS: 'Dual positivity' at NTD/DS screening may
anticipate pregnancy complications. The finding of trisomy 16 confined to the
placenta and FGR in 4 cases suggests that at least some fetuses with growth
restriction may suffer from a distinct placental disease. Maternal serum
screening may have implications different from DS and NTD, as demonstrated by the
2 cases with triploidy and incomplete hydatiform mola, the 4 cases with placental
trisomy 16, and the 4 cases of FGR of the 5 fetuses without chromosome
abnormalities. As the pathologic outcome of these pregnancies is more important
than the mere serum screening results, we feel that these cases need a strict
work-up, including CVS, amniocentesis and ultrasound studies to better address
the obstetrical management.
PMID- 9650658
TI - Early antenatal diagnosis of cardiac defects using transvaginal Doppler
ultrasound: new perspectives?
AB - OBJECTIVE: Cardiac defects are the most prevalent congenital anomalies. Screening
policies have adopted an 18- to 22-week ultrasound scan to detect such anomalies.
However, diagnosis may be feasible early in pregnancy using transvaginal Doppler
ultrasound. METHODS: Transvaginal ultrasound, including nuchal translucency (NT)
measurement, is routinely performed at 10-13 weeks of gestation at our
department. Complementary arterial and venous blood flow Doppler evaluation is
also performed in cases of increased NT as a part of an ongoing research project.
RESULTS: Ultrasound revealed complete atrioventricular septal defects in 2
trisomic fetuses (trisomy 18 and 21) at 12 and 13 weeks of gestation,
respectively, with increased NT and abnormal venous blood flow velocity.
CONCLUSIONS: Increased NT has been associated with major chromosomal anomalies
and is being increasingly related to cardiac defects. Considering that venous
blood flow patterns may provide additional clues to the cardiac function, it may
be useful as a complementary tool for the earlier diagnosis of structural cardiac
anomalies.
PMID- 9650659
TI - Blood gas and pH in the human fetus with severe anemia.
AB - Leiden University Hospital is the national referral center for the management of
fetal isoimmunization in The Netherlands. In this observational study, blood gas
and acid-base measurements from 286 pretransfusion samples and 214 paired
posttransfusion samples of 113 fetuses were analyzed. In umbilical arterial
blood, we found a significant positive correlation between the degree of anemia
and pH, as well as a significant negative correlation between degree of anemia
and pO2. However, umbilical venous blood gas and pH remained virtually unchanged
even in severe anemia. During intrauterine transfusion with unbuffered adult red
cells, there was a small but statistically significant decrease of pH and pO2 in
fetal blood. We conclude that severe fetal anemia is associated with decreased
umbilical arterial pH, but that umbilical venous pH remains normal until shortly
before death.
PMID- 9650660
TI - Pastoral care utilization among women electing pregnancy termination for fetal
anomalies.
AB - OBJECTIVE: To identify determinants of requesting pastoral care (PC) at the time
of pregnancy termination for fetal anomalies. METHODS: PC was provided by a
hospital-based chaplain. Data were reviewed for 88 women who elected pregnancy
termination. Nominal logistic regression and Kruskal-Wallis and Student t tests
were used as appropriate. RESULTS: None of 37 women who underwent dilatation and
curettage (D&C) or dilatation and evacuation (D&E) requested PC as compared with
40 of 51 patients who underwent prostaglandin induction of labor (p < 0.001). The
decision to seek PC was related to gestational age (p < 0.001), but not to
maternal age, prior termination of pregnancy, gravidity, parity, racial
background, or insurance status. The gestational age was also a significant
predictor of the procedure performed (p < 0.001). D&C/D&E were significantly more
likely to be performed at earlier gestational ages. Women seeking PC were less
likely to have experienced previous pregnancy loss or the death of a child. Among
women who sought PC, 20% had experienced previous pregnancy loss or the death of
a child, as opposed to 54% of women in the prostaglandin group who did not seek
PC (p = 0.03). In the D&C/D&E group, the figure was 46%. CONCLUSIONS: Utilization
of PC is much more frequent among women undergoing prostaglandin induction of
labor than D&C/D&E. Determinants of seeking PC are related to issues congruent
with choices of the termination procedure. Patients who experienced a previous
pregnancy loss or the death of a child are also less likely to feel the need, or
do not want, chaplaincy involvement.
PMID- 9650662
TI - Design and development strategy for the rotary blood pump.
AB - Development of an antitraumatic antithrombogenic and durable blood pump is a very
difficult task. Based upon this author's experience of over 35 years in the
development of various types of cardiac prostheses, development strategies for a
rotary blood pump are described. A step-by-step development strategy is thus
proposed. Initially, the development of a 2 day antitraumatic pump (Phase 1)
would be made. Then, conversion of this pump to a 2 week antithrombogenic pump
(Phase 2) should be attempted. After the successful development of the Phase 2
pump, the conversion of this device to a durable, implantable, and long-term
blood pump (Phase 3) should be established. Based upon this development strategy,
2 rotary blood pumps, namely, the axial flow blood pump and the centrifugal blood
pump, have been developed in less than 6 years with modest development costs.
PMID- 9650661
TI - Coenzyme Q10 fetal plasma levels.
AB - OBJECTIVE: This study aims at determining a cutoff value differentiating the
fetal from the adult coenzyme Q10 (CoQ10) values and comparing substantial
increases in CoQ10 plasma levels in fetuses with hypoxic hypoxia and nonimmune
fetal hydrops. METHODS: We have selected 61 pregnancies and determined the CoQ10
levels in fetal and maternal samples obtained by cordocentesis. Our study
included a control group and pregnancies with intrauterine growth retardation, Rh
isoimmunization, nonimmune fetal hydrops, and fetal malformations. RESULTS: To
differentiate the fetal from the adult values we have set 0.3 mg/ml as the cutoff
value. The CoQ10 were higher only in fetuses with hypoxic hypoxia and nonimmune
hydrops. CONCLUSION: Normal fetal CoQ10 plasma levels are lower than 0.3 mg/ml.
PMID- 9650663
TI - Cleveland Clinic continuous flow blood pump: progress in development.
AB - The Cleveland Clinic continuous flow blood pump is the central element of our
innovative ventricular assist system (IVAS). Recent progress has been made in the
design/fabrication of a pulsatile mock loop, journal bearing materials testing,
and evaluation of a system control algorithm. These results have allowed an
acceleration of our program.
PMID- 9650664
TI - Eccentric roller type total artificial heart designed for implantation.
AB - In the process of developing a completely implantable total artificial heart
system, we have made an eccentric roller type total artificial heart and
evaluated it by means of a mock circulatory system and by an acute animal
experiment. The actuator of the artificial heart consists of 2 cylindrical drum
type rollers which squeeze 2 blood chambers. The blood chambers are made of
silicone rubber and are torus in shape. There is no valve used in this artificial
heart. The artificial heart appears to be a nearly circular cylinder,
approximately 10 cm in length and 8 cm in diameter. In the Donovan mock test, the
artificial heart worked at a roller speed of 100-125 rpm with flow rates of 2.5
3.0 L/min for the right side and 3.2-3.8 L/min for the left side, respectively.
The electric power consumption was 19.0-24.7 W. Our artificial heart is
characterized by an ejection of blood alternatively in the pulsatile mode without
need for reversing the motor. In the ex vivo evaluation, circulation of an adult
sheep was maintained with this artificial heart for 4 h.
PMID- 9650665
TI - Implantable micropump system for augmented liver perfusion.
AB - Liver cirrhosis, a worldwide health problem, decreases the blood flow through the
liver. This in turn leads to dangerous portal hypertension and decreased
metabolic function within the liver. To improve this situation, a new concept is
proposed which involves introducing a microaxial blood pump into the portal vein.
This device is intended to increase blood flow through the liver and to enhance
hepatic function. Furthermore, high pressures will be reduced to physiological
levels. The microaxial pump with its single stage impeller is powered by a
proximally integrated microelectric motor. The pump unit is completely immersed
within the blood vessel. Heat caused by electrical and mechanical losses will be
transported into the blood. In vitro optimization of the pump design was
accomplished using both hydraulic and hemolysis tests.
PMID- 9650666
TI - Development of the small caliber centrifugal blood pump.
AB - Regarding the development of a centrifugal blood pump to be connected directly
with small diameter tubings for pediatric use while minimizing hemolysis, we have
studied the inlet port side configurations of a pump using both a hemolysis test
and computational fluid dynamics (CFD) analysis. We have conducted a hemolysis
test on 2 models. The tapered shape inlet has proven to be lower in the index of
hemolysis (IH) than the straight shape. CFD analyses utilizing expanded flow
paths indicated that the flow velocity decreased as the fluid path became larger
within the tapered nozzle. When entering the pump chamber, the flow rushed in at
a greater velocity through the straight nozzle due to its small diameter. The
straight shape showed an abrupt change in pressure around the entrance of the
pump chamber while the tapered shape did not. The flow inlet angle of the
straight model was observed to be larger than that of the tapered model because
of its smaller turning radius.
PMID- 9650667
TI - An implantable centrifugal blood pump with a recirculating purge system (Cool
Seal system).
AB - A compact centrifugal blood pump has been developed as an implantable left
ventricular assist system. The impeller diameter is 40 mm, and pump dimensions
are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in
a pump weight of 400 g including a brushless DC motor. The weight of a second
prototype pump was reduced to 280 g. The entire blood contacting surface is
coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates
of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power
consumption have been measured. A newly designed mechanical seal with a
recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal
system, the seal temperature is kept under 40 degrees C to prevent heat
denaturation of blood proteins. Purge fluid also cools the pump motor coil and
journal bearing. Purge fluid is continuously purified and sterilized by an
ultrafiltration unit which is incorporated in the paracorporeal drive console. In
vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate
(normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments
are currently ongoing using calves. Via left thoracotomy, left ventricular (LV)
apex descending aorta bypass was performed utilizing an expanded
polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left
thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5
9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb
levels were measured at less than 15 mg/dl. The seal system has demonstrated good
seal capability with negligible purge fluid consumption (<0.5 ml/day). In both
calves, the pumps demonstrated trouble free continuous function over 6 month (200
days and 222 days).
PMID- 9650668
TI - Performance of a continuous flow ventricular assist device: magnetic bearing
design, construction, and testing.
AB - A new centrifugal continuous flow ventricular assist device, the CFVAD III, which
is fully magnetic bearing suspended, has been developed. It has only one moving
part (the impeller), has no contact (magnetic suspension), is compact, and has
minimal heating. A centrifugal impeller of 2 inch outer diameter is driven by a
permanent magnet brushless DC motor. This paper discusses the design,
construction, testing, and performance of the magnetic bearings in the unit. The
magnetic suspension consists of an inlet side magnetic bearing and an outlet side
magnetic bearing, each divided into 8 pole segments to control axial and radial
displacements as well as angular displacements. The magnetic actuators are
composed of several different materials to minimize size and weight while having
sufficient load capacity to support the forces on the impeller. Flux levels in
the range of 0.1 T are employed in the magnetic bearings. Self sensing electronic
circuits (without physical sensors) are employed to determine the impellar
position and provide the feedback control signal needed for the magnetic bearing
control loops. The sensors provide position sensitivity of approximately 0.025
mm. A decentralized 5 axis controller has been developed using modal control
techniques. Proportional integral derivative controls are used for each axis to
levitate the magnetically supported impeller.
PMID- 9650669
TI - Fine trabecularized carbon: ideal material and texture for percutaneous device
system of permanent left ventricular assist device.
AB - The development of a percutaneous artificial internal organ system requires a
reliable biocompatible connection between the external environment and the inside
of the human body. Such is necessary for the success of a permanent left
ventricular assist device. However, the search for a satisfactory interface at
the epidermal level has proven to be difficult. Carbon has been proposed for this
application, but its texture does not typically promote ingrowth from surrounding
tissue. We have therefore employed a new processing method to produce a fine
trabecularized carbon implant. The method for preparing the implant involves
infiltrating low temperature pyrolytic carbon into the surface of a carbon core
which is wrapped with carbon fabric. This results in a tightly woven porous
structure of carbon (carbon fiber diameter: 35-50 microm, maximal pore size >200
microm) with gradually increasing porosity from 15-75%. We implanted test samples
percutaneously in a calf for in vivo histological evaluation. Thirty days after
implantation epidermal downgrowth was minimal. Microscopic analysis revealed that
a thin fibrous capsule surrounded the implant, and mature connective tissue with
accompanying blood vessels filled the pores of the fine trabecularized carbon
layer. From these results we suggest that fine trabecularized carbon is ideally
suited for a percutaneous device system in a permanent left ventricular assist
device.
PMID- 9650670
TI - Development of a flow estimation and control system of an implantable centrifugal
blood pump for circulatory assist.
AB - A bypass flow rate estimation and control system (BECS) for an implantable
centrifugal blood pump (ICBP) has been developed in our institute. The estimated
flow rate (EF) of the ICBP was derived from the electric power consumption, the
rotating speed of a motor, and the blood viscosity presumed by the hematocrit and
body temperature. The error in the EF was 0.5 +/- 0.4 L/min in in vivo
experiments for 40 days. The rotating speed of the motor was controlled
automatically every 200 ms to bring the EF in accord with the desired flow rate
(DF). The reactivity and accuracy of the BECS were investigated in in vitro and
in vivo experiments. The ICBP was operated by the BECS in a mock circuit in
parallel with a pulsatile ventricular assist device (PVAD) to simulate left heart
bypass. The reactivity was evaluated by changing the DF from 7 L/min to 5 L/min
at an afterload of 160/97 mm Hg. To evaluate the accuracy of the BECS, the ICBP
was driven under the aortic pressure of 110/85 mm Hg in the abdominal wall of an
adult goat (70 kg). The DF was set at 5 L/min for 4 min for the goat in an awake
condition. It took 13 s to change the flow rate in the in vitro experiment. The
measured flow rate (MF) was maintained at 5.0 +/- 0.2 L/min by the BECS in vivo.
In conclusion, the BECS has moderate reactivity and accuracy.
PMID- 9650671
TI - Intrathoracic and intraabdominal wall implantation of a centrifugal blood pump
for circulatory assist.
AB - An implantable centrifugal pump (ICP) 320 ml in volume and 830 g in weight has
been developed for prolonged circulatory assist. The antithrombogenicity of the
ICP is provided by a balancing hole in the center of the impeller. The
watertightness and histocompatibility of the ICP are supported by its silicone
ring seal and its casing of titanium and acrylic resin, respectively. The total
efficiency of the ICP was 30% at a 5 L/min flow rate and a 100 mm Hg head. The
heat generation, watertightness, and anatomical fitting of the ICP were assessed
in an intrathoracic implantation in a goat (66 kg) and in an intraabdominal wall
implantation in a goat (70 kg). Warfarin was given for anticoagulation in each
experiment to keep the prothrombin time around 1.7 times that of the control. The
temperatures of the pump surface, the pleura, and the room were measured every 3
h. Anatomical fitting was evaluated by pathological observation after the
termination of the experiment. The ICP could run for 40 days in the chest cavity
and for 11 days in the abdominal wall. The temperature of the motor remained
about 1.8 degrees C higher than the reference in both experiments. The ICP was
completely covered by a layer of smooth fibrous tissue. The moisture content of
the seals remained normal. Although a small amount of atelectasis was found in
the lingula, neither lung adhesion nor necrotic change of the chest wall was
observed. The inflammation of the surrounding tissue including foreign body
reaction and thermal burn was minimal. In conclusion, the ICP has satisfied in
vivo testing of its watertightness, exothermicity, and anatomical fitting.
PMID- 9650672
TI - Clinical experiences of percutaneous cardiopulmonary support: its effectiveness
and limit.
AB - In recent years, several types of centrifugal pumps have been widely used as the
main pumps for cardiopulmonary bypass (CPB) and postcardiotomy cardiac support.
From April 1990 to March 1997, a percutaneous cardiopulmonary support (PCPS)
system was used in 20 patients with an average age of 58 years (13 males and 7
females). They comprised 11 ischemic, 6 valvular, 2 aortic, and 1 congenital
heart disease patients. Our PCPS system consists of a centrifugal pump
(BioMedicus BP-80), an oxygenator, and a reservoir. The entire blood contacting
surface, including that of the thin wall cannulas, is coated by heparin bonded
materials. As a result of this new technology, this system can be used for the
long term without systemic heparinization. No major critical thrombi were
revealed inside the pumps or circuits. Of the 20 patients, 7 (35%) (Group 1)
could be weaned from PCPS, and the remaining 13 (Group 2) could not. In Group 1
although 2 patients suffered from renal failure and pneumonia, respectively, both
were discharged from our hospital. The long-term survival rate was 35%. In Group
2 cerebral vascular damage was recognized in 3 patients, renal failure in 4,
multiple system organ failure in 4, bleeding in 2, arrhythmia in 1, and leg
ischemia in 2. Pulse pressure was significantly elevated due to the recovery of
the native heart in Group 1, 2 days after support. However, in Group 2, it did
not elevate, and the left ventricular ejection fraction was less than 30%,
associated with high left atrial pressure. In conclusion, this heparin coated
PCPS system was very simple and easy to control. It demonstrated long-term
biocompatibility and was very effective in recovering deteriorated cardiac
function. Quicker application of this system can play an important role in
preventing severe complications and obtaining better clinical results. If long
term support is necessary, a ventricular assist device (VAD), which is more
powerful, durable, and biocompatible, has to be applied instead of PCPS.
PMID- 9650673
TI - Left centrifugal pump cardiac assist with transseptal percutaneous left atrial
cannula.
AB - Left cardiac support postcardiotomy requires a second operation for removal of
the atrial cannula following weaning from assistance. To avoid the risk of this
procedure, we used a transseptal cannula prototype. The cannula was introduced
percutaneously through the femoral vein and advanced into the left atrium guided
by the finger of the surgeon. Optimal positioning of the tip of the cannula was
verified by perioperative transesophageal echocardiography. A long arterial
cannula was positioned in the descending aorta via the femoral artery and a
Carmeda circuit with a centrifugal pump was connected to both cannulas. This
procedure was used in 3 patients with low cardiac output who underwent emergency
surgery, a 63-year-old patient referred for aortic and mitral valve replacement,
a 54-year-old man for aortic valve replacement, and a 64-year-old patient in the
acute phase of myocardial infarction after myocardial revascularization. The
assistance was used systematically at the end of the operation. The assist flow
was 1.2-2.6 L/min. The patients were all weaned from support between 18 h and 8
days later. No complications related to the device occurred. Both cannulas were
removed surgically from the femoral vessels without reopening the chest. This new
procedure is of interest for 2 reasons: the systematic implantation allows for
early assistance, and the use of a percutaneous approach avoids the risk of
reopening the chest. More cases are needed to confirm this initial good
impression.
PMID- 9650674
TI - Safety of beating heart anastomosis during video-assisted coronary surgery
attested by cardiac troponin I.
AB - Our objective was to evaluate the safety of coronary anastomosis on the beating
heart by measuring the release of cardiac troponin I during minimally invasive
coronary artery bypass grafting (MICABG). Cardiac troponin I (cTnI) is a reliable
marker of cardiac ischemia during heart operations under cardiopulmonary bypass
(CPB). Ten patients (8 males and 2 females, aged 41-63) underwent MICABG with
single vessel bypass grafting for left anterior descending coronary artery (LAD)
stenosis (n = 7) or occlusion (n = 3). Video-assisted surgery with left anterior
minithoracotomy was performed in all patients. Serial venous blood samples were
collected for measurement of cTnI before LAD occlusion (T0), during anastomosis
(T1) and 10 min (T2), 6 h (T3), 24 h (T4), 48 h (T5), and 72 h (T6) after
coronary reperfusion. The assay method used a specific enzyme-linked
immunosorbent Stratus autoanalyzer. Control coronary angiography was performed in
all patients. There were no operative complications or reoperations for bleeding.
The cTnI concentrations were expressed in ng/ml +/- SD. The mean cTnI level was
less than 3.05 +/- 0.2 ng/ml (range 0-32.8). Values were T0 = 0, T1 = 0.4 +/-
0.03, T2 = 1.15 +/- 0.2, T3 = 2.16 +/- 0.6, T4 = 1.5 +/- 0.3, T5 = 0.6 +/- 0.02,
and T6 = 0.4 +/- 0.01. Angiography showed patent grafts in 9 patients. In one
case, early internal thoracic artery (ITA) graft occlusion in a patient with 2
vessel disease was correlated with a higher cTnI concentration (17.8 ng/ml).
Percutaneous angioplasty was performed on the right coronary artery, complicated
with dissection and cardiac failure. This patient died 3 months after the MICABG
despite support from a ventricular assist device. In conclusion, collateral
circulation developed in the setting of chronic coronary occlusion may be
efficient for myocardial preservation during short periods such as coronary
anastomosis. cTnI immunoassay confirmed the safety of coronary anastomosis on the
beating heart during minimally invasive coronary operations.
PMID- 9650675
TI - Summary of the 5th congress of the International Society for Rotary Blood Pumps,
Marseille, France, 1997.
PMID- 9650676
TI - Limitations and obstacles encountered in developing a practical hybrid hepatic
assist device.
PMID- 9650677
TI - The syndrome of acute near-total intrauterine asphyxia in the term infant.
AB - Eleven term infants sustained an acute, near-total intrauterine asphyxia at the
end of labor. Imaging studies documented a consistent pattern of injury in
subcortical brain nuclei, including thalamus, basal ganglia, and brainstem; in
contrast the cerebral cortex and white matter were completely or relatively
spared. This pattern of injury correlated with the acute and long-term neurologic
syndromes in these patients. Four patients had a severe neonatal encephalopathy
that included prominent signs of brainstem dysfunction. The other seven patients
had a moderate neonatal encephalopathy. Three of these patients had dystonia
consistent with basal ganglia injury; all seven remained normocephalic and had
good cognitive outcomes consistent with sparing of cerebral cortex and white
matter. Finally, in all 11 patients, injury to organs other than the brain was
usually subtle. The distribution of injury in these patients reflects the
hierarchy of metabolic needs that are unmet after a severe, sudden disruption of
substrate supply as occurs in an acute, severe asphyxia. Thus, the higher
metabolic rate of the brain compared with other organs explains the significant
neonatal encephalopathy with relative sparing of nonbrain organs. Similarly, the
higher metabolic rate of subcortical nuclei compared with cerebral hemispheres
explains the preponderance of subcortical damage. This clinical and imaging
syndrome is in contrast with that seen in more prolonged but less severe
intrauterine asphyxia, in which shunting of blood flow from nonbrain organs to
the brain and from cerebral hemispheres to the thalamus and brainstem renders
nonbrain organs and cerebral hemispheres most vulnerable.
PMID- 9650678
TI - Visual function in children with merosin-deficient and merosin-positive
congenital muscular dystrophy.
AB - This study evaluates whether abnormalities of visual function are present in
children with congenital muscular dystrophy and whether these, if present, are
associated with merosin status or magnetic resonance imaging (MRI) findings.
Twenty children (age range 5-17 years) with a diagnosis of classical congenital
muscular dystrophy were assessed on visual acuity, stereopsis, and visual fields
and the results compared with merosin status and MRI findings. Visual-evoked
potential results were available for 14 of 20 children. All 20 children revealed
normal results on all the clinical tests assessing visual function, irrespective
of their merosin status or of MRI findings. Visual-evoked potentials were normal
in the children with merosin-positive congenital muscular dystrophy but were
abnormal in those with merosin deficiency. Unlike the other forms of congenital
muscular dystrophy, which are associated with structural brain changes and eye
involvement, visual function was always normal in the classical form of
congenital muscular dystrophy. Interestingly, visual function was normal also in
the group of children with merosin-deficient congenital muscular dystrophy who
manifested white matter changes involving the occipital lobes on MRI and abnormal
visual evoked potentials. Further studies are needed to specify the nature of the
white matter changes observed with MRI and the reason for the dissociation
between clinical and neurophysiologic findings.
PMID- 9650679
TI - Antiepileptic drugs and atypical evolution of idiopathic partial epilepsy.
AB - Six patients with classic benign epilepsy of childhood with centrotemporal
spikes, treated with carbamazepine (four patients) or sodium valproate (two
patients) evolved atypically because the epileptic disorder, diffusion of the
electroencephalographic (EEG) discharges during wakefulness, and continuous spike
and-wave during slow sleep associated with severe neuropsychologic abnormalities
worsened. These features appeared after a seizure-free interval varying for 2
weeks to 1 year 6 months after initiating therapy and remitted when the previous
anticonvulsant drug was discontinued and either substituted with another drug or
the patient was left without any treatment. Once the initial antiepileptic drug
was discontinued and after a period roughly proportional to the duration of the
clinical-EEG complication, the evolution of the patients' seizures was not
unusual for this type of epilepsy, with patients eventually becoming free of both
seizures and medication and reaching normal school achievement. The clinical
complications cannot be attributed solely to the drugs. It must also be related
to the underlying substract (i.e., the specific epileptic syndrome involved) that
in some patients becomes susceptible to atypical evolution when either product is
administered.
PMID- 9650680
TI - Treatment of type I spinal muscular atrophy with noninvasive ventilation and
gastrostomy feeding.
AB - Type I spinal muscular atrophy (SMA) is a rapidly progressive, degenerative
neuromuscular disease of infancy. In severe SMA, weakness, hypotonia, and bulbar
involvement lead to progressive respiratory insufficiency and swallowing
dysfunction, which are frequently complicated by aspirations. There are few
studies reported in the literature that address the respiratory management of
type I SMA. This article reports the results of treating four patients with
infantile SMA with noninvasive positive pressure ventilation and gastrostomy
feeding. All patients had gastroesophageal reflux disease, which was managed
medically. Despite these therapies, survival was only 1 to 3.5 months after
presenting with severe aspirations. The treatment strategy, which can be
effective in less rapidly progressive neuromuscular diseases, did not alter the
very poor prognosis of type I SMA. The treatment options are reviewed, and a
strategy designed to optimize quality of life for infants with this fatal disease
is presented.
PMID- 9650681
TI - Dysarthria in children with cerebellar or brainstem tumors.
AB - Speech features were perceptually analyzed in two groups of children. The first
group (n = 6) had undergone cerebellar tumor resection, and the second group (n =
6) included children with brainstem tumors. Children belonging to the first group
became dysarthric after a postoperative mute phase. Slow speech rate was a
specific feature, but scanning speech and irregular articulatory breakdown (i.e.,
prominent characteristics in adult ataxic dysarthria) were not observed. In the
second group, hypernasality was a prominent characteristic and resembled flaccid
dysarthria in adults. These findings suggest that acquired childhood dysarthria
needs a proper classification.
PMID- 9650682
TI - Liposteroid (dexamethasone palmitate) therapy for West syndrome: a comparative
study with ACTH therapy.
AB - Dexamethasone palmitate (liposteroid) was used for the treatment of West syndrome
and compared with adrenocorticotropic hormone (ACTH) therapy. A single
intravenous injection of liposteroid (0.25 mg/kg) was administered seven times in
3 months (total dosage = 1.75 mg/kg) to five symptomatic patients with West
syndrome, aged 4-11 months. ACTH (0.025 mg/kg/day) was administered
intramuscularly for 6 weeks according to the conventional therapy in Japan (total
dosage = 0.625 mg/kg) to five symptomatic patients with West syndrome, aged 6-10
months. Nodding spasm and hypsarrhythmia on EEG disappeared in all patients in
the liposteroid therapy group within four doses; however, partial seizures and
focal spikes on EEG reappeared in three patients 2 months after the end of
liposteroid therapy. In the ACTH therapy group, nodding spasm and hypsarrhythmia
on EEG similarly disappeared during treatment in all patients, but nodding spasm
reappeared 2 months after therapy in two patients and partial seizures reappeared
in one patient 3 months after therapy. No notable adverse reactions occurred in
the liposteroid group, but transient dysfunction of the thyroid and anterior
pituitary gland and increased levels of serum cortisol were experienced in the
ACTH group. These results suggest that glucocorticoid incorporated in a lipid
emulsion is useful for the treatment of West syndrome.
PMID- 9650684
TI - Ultracytochemical analysis of E-PTA-positive synaptic junctions in postmortem
examined brains with neurologic disorders.
AB - The synaptic junctions from four postmortem-examined brains were studied
ultracytochemically, using the ethanolic phosphotungustic acid (E-PTA) method. A
noteworthy finding was the presence of variable-shaped vesicles that were not
observed in the control E-PTA-treated preparations. This structural change in
synaptic junctions is thought to represent a degenerative process. It is
suggested that the neuronal transmission in brains with acquired neuropathologic
abnormalities may be impaired because of the degenerative change in synaptic
junctions.
PMID- 9650683
TI - Neurophysiologic evaluation of long-term desferrioxamine therapy in beta
thalassemia patients.
AB - Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age
and maintained on long-term desferrioxamine (DFO) treatment, were examined by
evoked potential and nerve conduction velocity studies to investigate a possible
involvement of the auditory, visual, somatosensory, or peripheral nervous
pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory
evoked potentials, and nerve conduction velocity studies were demonstrated in
25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated
involvement of multiple neural pathways. Subclinical involvement of the auditory
pathway was statistically associated with higher mean daily DFO dose and longer
duration of DFO therapy, whereas abnormalities regarding the somatosensory
pathways were related to older age, longer mean duration of DFO therapy, and
lower serum copper levels. Involvement of the peripheral nervous system was
related to lower serum copper levels. Multiple involvement of neural pathways was
related to longer mean duration of DFO therapy. We conclude that risk factors
related to long-term DFO treatment are only partly responsible for the
subclinical involvement of neural pathways demonstrated in beta-thalassemia major
patients.
PMID- 9650685
TI - mtDNA nt3243 mutation, external ophthalmoplegia, and hypogonadism in an
adolescent girl.
AB - A 14-year-old girl presented with a 3-month history of easy fatigue and exercise
intolerance, especially when climbing stairs. She had a mild ptosis and mild
limitation of upward gaze. Her puberty was delayed, and she manifested
hypogonadotrophic hypogonadism. Serum lactic and pyruvic acids were elevated.
Cranial magnetic resonance imaging was normal. Muscle biopsy documented typical
ragged-red fibers. A point mutation at nucleotide 3243 in the tRNALeu(UUR)
(typical mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
episodes (MELAS) mutation) was detected in mitochondrial DNA from both blood and
muscle tissues, indicating that our patient was suffering from a mitochondrial
myopathy. Hypogonadism may be a manifestation of the MELAS nucleotide 3243
mutation.
PMID- 9650686
TI - Dancing eye syndrome and hyperphosphatasemia.
AB - An 11-month-old boy with a relapsing dancing eye syndrome associated with
elevation of serum alkaline phosphatase, lactate dehydrogenase, and
aminotransferase activities is reported. During two clinical episodes the serum
alkaline phosphatase activity increased up to four times the upper reference
limit, remained elevated for a few weeks and normalized gradually in parallel
with clinical improvement under steroid therapy. We found no evidence of liver or
bone pathology nor of a neural crest tumor. The association between dancing eye
syndrome and hyperphosphatasemia has not yet been described. The beneficial
effect of the steroid therapy strengthens the hypothesis of an autoimmune origin.
PMID- 9650687
TI - Focal pachypolymicrogyria in three siblings.
AB - The malformation of focal pachypolymicrogyria might be the manifestation of an X
linked recessive disorder according to the results of this study. Three siblings
revealed focal pachypolymicrogyria on magnetic resonance imaging (MRI) and had a
strong family history of epilepsy and mental retardation. All three siblings had
the same mother; the father of Patient 1 was not related to the mother, but the
father of Patients 2 and 3 was related to her. The MRI of the father of Patients
2 and 3 demonstrated focal pachypolymicrogyria. The mother's MRI was normal. In
this family, epilepsy or mental retardation was found mainly in the males
(Patient 3 was an exception), and they were all born to female members of this
family, not male. Patient 3 was probably a homozygote with an X-linked recessive
inheritance, and therefore, she demonstrated the most severe clinical findings.
PMID- 9650688
TI - Pseudotumor cerebri in Lyme disease: a case report and literature review.
AB - Pseudotumor cerebri is an unusual presentation of Lyme disease. The case of an 8
year-old girl with pseudotumor cerebri secondary to acute neuroborreliosis is
reported. She presented with acute onset of headache, papilledema, sixth nerve
palsy, increased intracranial pressure, and cerebrospinal fluid pleocytosis.
Serum and cerebrospinal fluid Lyme antibodies were positive. Twelve reported
cases that mostly presented with systemic findings and signs of Lyme disease
before development of pseudotumor cerebri were reviewed. We conclude that acute
neuroborreliosis can present with pseudotumor cerebri as an initial
manifestation. It is important to include Lyme disease in the differential
diagnosis of pseudotumor cerebri in an area endemic for Lyme disease.
PMID- 9650689
TI - Successful treatment of progressive myoclonus epilepsy with TRH.
AB - Thyrotropin-releasing hormone (TRH) is sometimes used for the treatment of
neurologic disorders such as intractable epilepsy and spinocerebellar
degeneration. A 14-year-old girl with progressive myoclonus epilepsy was treated
with intravenous TRH for 12 months. Clinical symptoms, such as cortical myoclonus
and cerebellar signs, were improved, and P25-N33 amplitudes of somatosensory
evoked potentials decreased after TRH therapy. P100 amplitudes on flash visual
evoked potentials and photosensitivity on electroencephalograms also decreased
but only temporarily. Changes in neurophysiologic findings after TRH therapy
indicate that TRH inhibits hyperexcitability in the sensorimotor cortex and the
visual cortex. Therefore, intravenous TRH therapy is recommended as an
alternative therapy in the treatment of progressive myoclonus epilepsy.
PMID- 9650690
TI - New syndrome with the Sakoda complex, bilateral anophthalmia, and cortical
dysgenesis.
AB - An 8-year-old Japanese boy had Sakoda complex (basal encephalomeningocele,
agenesis of the corpus callosum, and cleft lip and/or palate) associated with
bilateral anophthalmia, dysgenesis of the cerebral cortex, severe mental
retardation, and intractable epilepsy as core symptoms and hemiparesis,
microcephalus, short stature, and hemivertebra. Tada and Nakamura described the
first case of the Sakoda complex associated with bilateral anophthalmia, cortical
dysgenesis, neonatal-onset seizures, and severe mental retardation. Fourteen
patients with the Sakoda complex with or without ocular dysplasia were reviewed.
It is proposed that these cases belong to a clinical entity that is
distinguishable from the remaining 12 patients because of bilateral anophthalmia,
cortical dysgenesis, and its resulting severe mental retardation and intractable
epilepsy. There is a possibility that these two cases are one severe end of
certain spectrum disorders in which certain common gene(s) might be implicated.
PMID- 9650691
TI - Hemimegalencephaly and Hirschsprung's disease: a unique association.
AB - A 2-year-old boy with hemimegalencephaly and Hirschsprung's disease is reported.
The unique association of these two entities is considered to be the presence of
a common insult or insults that affect the innervation of the bowel and the
formation of the cerebral cortex. Short-segment subtype of Hirschsprung's disease
may suggest that this effect occurred between the eighth and twelfth weeks of
gestation. Although there is a well-known coexistence of Hirschsprung's disease
with the malformations that share a common neurocristopathic origin
(abnormalities of neural crest cell growth, migration, or differentiation), a few
extremely rare cases, as in this case, might reflect the coexistence of
Hirschsprung's disease with a cerebral malformation (i.e., hemimegalencephaly)
that is a nonneurocristopathic entity by itself.
PMID- 9650692
TI - Parkinsonian syndrome complicating systemic lupus erythematosus.
AB - Two girls with florid extrapyramidal parkinsonism complicating systemic lupus
erythematosus (SLE) are reported. One patient (15 years old) presented with
extreme rigidity, irritability, and mutism initially diagnosed as acute
psychosis. Examination revealed severe extrapyramidal akinetic mutism, along with
marked restlessness. CT and MRI imaging of the brain were unremarkable. EEG
revealed moderate generalized disturbance of background activity. 99mTc-HmPAO
SPECT cerebral scanning detected decreased regional cerebral blood flow at the
basal ganglia. Dopamine-agonist drugs led to complete recovery after 3 months,
along with normalization of EEG and SPECT alterations. The second patient (16
years old) was assessed for progressive bradykinesia and apathy impeding her
active daily activities, and she was suspected to have developed depression.
Neurologic assessment revealed a parkinsonian syndrome that was less severe than
that of the first patient. The EEG showed mild disturbance of background
activity, and 99mTc-HmPAO SPECT demonstrated impaired regional cerebral blood
flow over the basal ganglia. A parkinsonian extrapyramidal syndrome complicating
SLE should therefore be taken into account in any patient with SLE presenting
with marked behavioral alterations, rigidity, or akinetic mutism.
PMID- 9650693
TI - LE or not LE--that is the question: an unsuccessful attempt to separate
lymphocytic infiltration from the spectrum of discoid lupus erythematosus.
AB - Lymphocytic infiltration of the skin (LIS) has been claimed to be a distinct
entity that differs from discoid lupus erythematosus (DLE) by the lack of
epidermal changes, negative immunofluorescence tests, and differences in the
composition of the inflammatory cell infiltrate. In studies that sought to
distinguish both conditions, however, cases of established lupus erythematosus
without epidermal involvement have not been considered. We studied 72 patients
with the clinical and histopathologic diagnosis of either LIS or DLE in regard to
the same clinical, histopathologic, immunofluorescence, and immunohistochemical
criteria. No significant differences were noted between cases with and without
epidermal involvement on the one hand and between cases with and without
immunofluorescence or clinical findings suggestive of lupus erythematosus on the
other. Based on our findings, it is not possible to separate LIS from the
spectrum of DLE.
PMID- 9650694
TI - Apoptosis in the pathogenesis of cutaneous lupus erythematosus.
AB - Defective regulation of apoptosis may play a role in the development of
autoimmune diseases such as systemic lupus erythematosus, in which the skin is a
prominent target. To our knowledge, however, the nature of epidermal changes in
cutaneous lupus erythematosus (LE) has not previously been investigated. We
investigated the involvement of apoptosis in cutaneous LE. A total of 44 lesional
skin samples from patients with cutaneous LE, 44 skin samples from patients with
scleroderma, five skin specimens from patients suffering from dermatomyositis,
and 13 normal skin samples were stained immunohistochemically with monoclonal
antibodies to Ki-67, p53 (DO-7), and bcl-2. The lesional skin from cutaneous LE,
except LE profundus, showed a marked increase in Ki-67- and p53-positive
keratinocytes, which were predominantly located in the basal layer of the
epidermis and follicle, and a drastic reduction in the number of bcl-2-positive
cells localized in the basal cell compartment. With TdT-mediated dUTP-biotin nick
end-labeling staining, we demonstrated that extensive apoptosis occurred in
almost the whole epidermis of cutaneous LE, except in cases of LE profundus. This
abnormal expression of Ki-67, p53, and bcl-2 and the occurrence of apoptosis in
the epidermis was also observed in epidermis from patients with dermatomyositis,
but not in that from patients with scleroderma.
PMID- 9650695
TI - Histopathologic differentiation between localized and systemic scleroderma.
AB - It is widely accepted that a histopathologic differentiation between localized
scleroderma (LS) and systemic scleroderma (SS) is not always possible. With the
objective of identifying differentiating histopathological features between them,
32 cases of LS and 19 cases of SS were reviewed. Histological features such as
the distribution, composition, and density of the inflammatory cell infiltrate,
thickness of the dermis, alterations of dermal collagen, and the presence of
calcification were evaluated in each case. On the basis of our observations, LS
and SS can be differentiated usually by the distribution and density of the
inflammatory infiltrate and by the involvement of the papillary dermis.
Inflammatory changes are more prominent in LS than in SS. Sclerosis of the
papillary dermis is frequently seen in LS but is absent in SS.
PMID- 9650696
TI - The asteroid bodies of sporotrichosis.
AB - Some believe that asteroid bodies (AB) in sporotrichosis are nonspecific and are
equivalent to the AB of sarcoidosis and other granulomatous diseases. We studied
25 skin biopsy specimens of sporotrichosis in which AB were demonstrated, ten of
them with Sporothrix-positive culture. Immunohistochemistry was performed in
paraffin-embedded biopsy specimens using an anti-Sporothrix antibody. The same
procedures were done with seven biopsy specimens of lobomycosis, which contained
AB within giant cells. These did not react with the anti-Sporothrix antibody, and
by electron microscopy they displayed filamentous and myelin figures similar to
the AB of sarcoidosis. In sporotrichosis, the AB are extracellular eosinophilic
structures, 15-35 microm in diameter, and located within abscesses. One to three
are found in a section. They consist of a central yeast, surrounded by
eosinophilic spicules. The yeast stains with the anti-Sporothrix antibody, while
the spicules do not. Therefore, AB in sporotrichosis are specific for disease.
Visualization of the spicules alone can lead to the demonstration of the AB in
adjacent sections, and thus is a useful clue in the diagnosis of sporotrichosis.
Sporotrichotic AB must not be confused with the intracellular AB seen in giant
cells of granulomatous reactions, which are filamentous and myelin figures that
contain lipid.
PMID- 9650697
TI - Detection of Epstein-Barr virus and HTLV-I in T-cell lymphomas of skin in Taiwan.
AB - Viral etiology has been associated with the pathogenesis of T-cell lymphomas of
skin (TCLS). Therefore, we studied the presence of Epstein-Barr virus (EBV) and
type I human T-cell lymphotropic virus (HTLV-I) in tumor cells of TCLS to
determine the significance of these viruses with the disease. A retrospective
study was conducted on the skin tissues from 28 Chinese patients with TCLS. We
used in situ hybridization, immunohistochemistry, and polymerase chain reaction
to determine the presence of viruses. Among the 28 cases, HTLV-I was only
detected in two cases with adult T-cell leukemia/lymphoma, not in other cases of
TCLS. This suggests that HTLV-I may not play a significant role in the
oncogenesis of TCLS in Chinese patients. Conversely, EBV was detected in 12 cases
(42.9%), including the secondary TCLS, large cell lymphoma, mycosis fungoides,
adult T-cell leukemia/lymphoma, and angiocentric lymphoma. Nevertheless, latent
membrane protein 1 was not detected in any of the EBV-positive cases. Neither was
any correlation found between the presence of EBV in TCLS and the prognosis or
the severity of the skin lesion. Although there is a close association of EBV
with a portion of TCLS, its pathogenic role needs further investigation.
PMID- 9650698
TI - p16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry.
AB - To determine whether variation in the level of expression of p16 and p21WAF1
(p21) is associated with critical stages in cutaneous melanoma development or
progression, the expression of these antigens was analyzed by
immunohistochemistry in 110 benign and malignant melanocytic lesions.
Differential expression of p16 protein has been reported in cutaneous melanocytic
lesions, with loss of expression associated with the invasive stage of tumor
development. Expression of p16 was seen in 31 of 35 benign melanocytic tumors
(89%), 11 of 12 in situ melanomas (92%), 19 of 38 invasive primary melanomas
(50%), and 16 of 25 metastatic melanomas (64%). There was a significant
difference in the expression level of p16 observed in in situ versus invasive
primary melanomas (p = 0.006), which is consistent with loss of normal p16
activity occurring in association with malignant tumor invasion. Overall, p21
levels were found to be low or undetectable in the majority of benign lesions,
with greater p21 expression seen in malignant tumors. p21 was expressed in 28% of
nevi, 60% of in situ melanomas, 61% of invasive melanomas, and 48% of metastatic
melanomas. Among primary invasive tumors, the frequency of p21 expression
increased with level of invasion (p < 0.01) and with increasing thickness (p <
0.01). However, differences in p21 expression were not clearly related to a
particular stage of melanoma development.
PMID- 9650699
TI - C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant
melanomas.
AB - The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded
sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi
(MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an
immunoperoxidase technique. Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs
showed positive reactions in some of the tumor cells (p = nonsignificant). In the
majority of the tumors the staining was located in nuclei and graded as moderate
to strong in intensity. The percentages of positively stained cells did not
differentiate the three types of tumor, although they were higher in the
melanocytic nevi. Most of the lesions with a significant dermal component did not
show stratification of staining with progressive descent into the dermis.
Positive staining for c-fos was also frequently found in the normal skin
constituents within and adjacent to the melanocytic tumors. In conclusion, the
pattern of expression of c-fos in routinely processed specimens does not
differentiate between SNs, MNs, and MMs.
PMID- 9650700
TI - A case of glomeruloid hemangioma associated with multicentric Castleman's
disease.
AB - Glomeruloid hemangioma is a term that was coined J.K.C. Chan and colleagues in
1990 because the condition is histopathologically similar to renal glomeruli. In
the three cases described to date, there have been signs of POEMS syndrome of
multicentric Castleman's disease. We present the case of a 44-year-old Korean
woman who developed glomeruloid hemangioma in association with multicentric
Castleman's disease and some features of POEMS syndrome. It is interesting that
in this patient, the first biopsy specimen revealed an immature vascular tumor
that could not be precisely classified and the second indicated glomeruloid
hemangioma. The present case may lend support to the suggestion that in POEMS
disease, some types of vascular proliferations develop in response to angiogenic
stimuli that show a spectrum of histopathologic features, and glomeruloid
hemangioma is one of the reactive vascular proliferations. We believe that the
primitive vascular tumor seen in the first biopsy specimen may be the most
immature stage of this spectrum.
PMID- 9650701
TI - Mycosis fungoides palmaris et plantaris or acral pagetoid reticulosis?
AB - There has been ongoing debate about the nature of Woringer-Kolopp disease
(unilesional pagetoid reticulosis). Despite the histologic resemblance to mycosis
fungoides, these lesions are typically solitary and indolent. Recently, cutaneous
plaques of epidermotropic lymphocytes restricted to acral sites resembling
Woringer-Kolopp disease were reported to show T-cell clonality, leading to the
designation mycosis fungoides palmaris et plantaris. We describe a similar case
of recurrent plaques on palms and soles of a 45-year-old man that persisted for
>14 years without other cutaneous or systemic disease. Histologically, the
lesions were comprised of epidermotropic atypical lymphocytes with sparse dermal
infiltrates. Immunohistochemically, the majority of intraepidermal lymphocytes
labeled as CD8-positive suppressor/cytotoxic T cells and expressed alphaE beta7
(CD103), an integrin associated with epitheliotropism. Polymerase chain reaction
studies revealed similar clonal gene rearrangements of T-cell receptors beta and
gamma in tissue from both palm and sole. In view of these findings, the diagnosis
of mycosis fungoides palmaris et plantaris may be appropriate. To date, however,
the lesions have remained localized and continue to resolve spontaneously. As
such, the behavior is similar to what has been described as pagetoid reticulosis.
Long-term follow-up will be necessary to determine the biologic potential of this
disease.
PMID- 9650702
TI - Membranocystic lesions in a patient with cytophagic histiocytic panniculitis
associated with subcutaneous T-cell lymphoma.
AB - A 51-year-old Japanese woman had erythematous, tender subcutaneous nodules on her
lower legs and buttocks, as well as fever, pancytopenia, and liver dysfunction.
Histopathologic examination of the nodules showed subcutaneous T-cell lymphoma
with cytophagocytosis and membranocystic lesions. Our patient was unique in
having the combination of cytophagic histiocytic panniculitis due to subcutaneous
T-cell lymphoma and membranocystic lesions.
PMID- 9650703
TI - Primary cutaneous Langerhans cell histiocytosis in an adult.
AB - A 76-year-old man with Langerhans cell histiocytosis was admitted with an
asymptomatic, dark red nodule on his left buttock. Histologic examination of the
nodule showed a dense dermal infiltrate of histiocytic cells with bean-shaped
nuclei; these cells reacted with antibodies to S-100 and CD1a. Ultrastructural
analysis showed Birbeck granules in the cytoplasm of the histiocytic cells.
Inguinal lymph node involvement subsequently developed in the patient and
cutaneous nodules recurred three times in the inguinal area. Four years have
passed since he first was admitted to our hospital with the cutaneous nodule on
his buttock, and he is doing well without any intensive treatment except wide
excision of the nodules and inguinal lymph nodes. We believe this case should be
classified as one of "benign" primary cutaneous Langerhans cell histiocytosis
based on the clinical course.
PMID- 9650704
TI - Synovial metaplasia in lipoma.
AB - We present a unique case of a lipoma with widespread synovial metaplasia. A 52
year-old woman had a recurrence 1 year after excision of a subcutaneous lipoma of
the neck. Histologically, the primary tumor was an ordinary lipoma. The recurrent
tumor was a myxoid lipoma with synovial metaplasia. The synovial metaplastic
process manifested as labyrinthlike clefts, which were lined by one or more
synovial-like cell layers. Ultrastructurally, the synovial metaplastic cell had
secretory, phagocytic, and fibroblastlike features.
PMID- 9650705
TI - Myxoid malignant fibrous histiocytoma mimicking papular mucinosis.
AB - Malignant fibrous histiocytoma is the most common type of soft tissue sarcoma in
late adulthood. The myxoid variant of malignant fibrous histiocytoma, also known
as myxofibrosarcoma, can develop in subcutaneous rather than deep soft tissue,
and the true extent of these superficial tumors is often underestimated. Patients
with these low-grade myxoid malignant fibrous histiocytomas have an excellent 5
year survival rate, and it is therefore important to recognize them. We present a
case with a superficial cutaneous accumulation of mucin that was diagnosed
clinically and histologically as papular mucinosis. In retrospect, a subcutaneous
presentation of myxofibrosarcoma should have been considered.
PMID- 9650706
TI - Syringomatous changes of eccrine sweat ducts associated with prurigo nodularis.
AB - Alteration of the eccrine sweat ducts has been observed in association with an
expanding list of conditions. To our knowledge, this phenomenon has not been
described in association with prurigo nodularis. We report on a 68-year-old man
with a fibrotic nodule on his chin that had been present for 8 months.
Microscopic examination showed marked hyperkeratosis overlying the epithelium.
There was also hypergranulosis, marked acanthosis, and irregular elongation of
the rete ridges. These findings were consistent with prurigo nodularis. In
addition, within the reticular dermis, there was marked fibrosis and a
proliferation of eccrine sweat ducts. The ducts were enlarged and varied from
cystic to rarely solid structures. Rare ducts formed a tadpole-shaped tail,
reminiscent of syringoma. The duct lining demonstrated a multilayered epithelium
that was three to eight cells thick, yielding a solid component to some of the
cysts. Although some of these features were similar to those of a syringoma, the
typical small gland proliferation and bilayered lining was not evident. This case
(a) demonstrates the association of syringomatous changes of eccrine sweat ducts
with yet another condition, prurigo nodularis, and (b) emphasizes the importance
of differentiating this benign reactive process from the malignant neoplasms
microcystic adnexal carcinoma and squamous cell carcinoma.
PMID- 9650707
TI - A review of tumor suppressor genes in cutaneous neoplasms with emphasis on cell
cycle regulators.
AB - Cells normally have five options. These include renewal or proliferation,
terminal differentiation, quiescence, senescence, and apoptosis. Many factors
interact with cell cycle regulators to direct the cells toward these different
options. Tumor suppressor genes play a pivotal role in this process. Alterations
in these genes may limit the options that cells have and thus play a significant
role in the multistep process of carcinogenesis. We will focus on tumor
suppressor genes and especially tumor suppressor genes that interact directly
with the cell cycle proteins.
PMID- 9650708
TI - Patterns versus mechanisms of cutaneous metastases.
PMID- 9650709
TI - Spiradenocylindroma--more than a coincidence?
PMID- 9650710
TI - Interactive CD34-positive fibroblasts and factor XIIIa-positive histiocytes in
cutaneous mesenchymal tumors.
PMID- 9650711
TI - p53 protein and Kaposi's sarcoma.
PMID- 9650712
TI - Cutaneous apocrine mixed tumor: derived from the apocrine duct of the folliculo
sebaceous-apocrine unit?
AB - We report a case of cutaneous mixed tumor (CMT) composed of tubular branching
structures lined by cells with apocrine characteristics. In addition, an apocrine
duct in the outer sheath of an hair follicle was connected to the mixed tumor, a
previously unreported finding. Follicular and sebaceous differentiation have been
described in CMT, leading some observers to suggest the existence of an apocrine
type of CMT and its presumed differentiation toward the folliculo-sebaceous
apocrine unit (FSAU). Our case demonstrated continuity of an apocrine duct in the
FSAU and lends support to the previous speculations about the histogenesis of
apocrine type of CMT.
PMID- 9650713
TI - Isolation and characterization of insulin in Russian sturgeon (Acipenser
guldenstaedti).
AB - Insulin was isolated from the pancreas of Chondrostean fish, the Russian
sturgeon, Acipenser guldenstaedti, by acid-ethanol extraction followed by ion
exchange and reverse-phase high-performance liquid chromatographies. The amino
acid sequence determined by automated Edman degradation is as follows: A-chain
(21-amino-acid peptide), H-Gly-Ile-Val-Glu-Gln-Cys-Cys-His-Ser-Pro-Cys-Ser-Leu
Tyr-Asp-Leu-Glu-As n-Tyr-Cys-Asn-OH; and B-chain (31-amino-acid peptide), H-Ala
Ala-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Va l-Cys-Gly-Glu
Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Asn-Lys-Val-OH. The sturgeon insulin appears to be
identical with one of two forms of paddlefish insulin and differs from the other
form by a single substitution in the A-chain, Asp15: His15. The amino acid
sequence of sturgeon insulin is more similar to the amino acid sequence of
mammalian insulins than of other fish insulins. Sturgeon insulin showed parallel
but weaker displacement than porcine insulin and pink salmon insulin in their
respective radioimmunoassays and was less potent than porcine insulin in
displacing radiolabeled porcine insulin bound to partially purified rat liver
plasma membranes.
PMID- 9650714
TI - Comparison of the binding of alpha-helical and beta-sheet peptides to a
hydrophobic surface.
AB - The induction and stabilisation of secondary structure for a series of
amphipathic alpha-helical and beta-sheet peptides upon their binding to lipid
like surfaces has been characterised by reversed phase high-performance liquid
chromatography (RP-HPLC). In addition, a series of peptides which have been shown
to switch from beta-sheet to alpha-helical conformation upon transfer from a
polar to a non-polar solution environment also have been studied. Binding
parameters related to the hydrophobic contact area and affinity for immobilised
C18 chains were determined at temperatures that ranged from 5 to 85 degrees C,
allowing conformational transitions for the peptides during surface adsorption to
be monitored. The results demonstrated that all peptides which adopt secondary
structure in solution also exhibited large changes in their interactive
properties. Overall, this study demonstrates that the hydrophobic face of each
amphipathic peptide dominates the binding process and that hydrophobic
interactions are a major factor controlling the surface induction of secondary
structure.
PMID- 9650715
TI - Synthesis and stabilization of amino and carboxy terminal constrained collagenous
peptides.
AB - Short collagenous peptides cross-linked at their amino and carboxy termini with
Lys-Lys-dimer template(s) were synthesized, and the effect of the cross-linking
on their stabilities was investigated by thermal denaturation experiments. Two
chemoselective ligations were used for the construction of the amino and the
carboxy cross-linked peptides. The thermal transition temperature (Tm) and the
standard free energies (deltaG(o)) of the cross-linked collagenous peptides
increased, and the thermal stabilization effect corresponded to an elongation by
two units of the Gly-Pro-Hyp triad. The van't Hoff enthalpy (deltaH(o)) and the
entropy (deltaS(o)) values of the cross-linked peptides increased with chain
elongation, although the increments were smaller than those of the linear
peptides. When the same chain lengths were compared, the deltaH(o) was increased
and the deltaS(o) was nearly the same or increased by the cross-linking. These
results suggest that the cross-linking of the collagenous peptides with the Lys
Lys-dimer template(s) for stabilization contributes to the enthalpic effect,
rather than the entropic effect.
PMID- 9650716
TI - NMR and quenched molecular dynamics studies of superpotent linear and cyclic
alpha-melanotropins.
AB - Conformational searching, computer simulations, synthesis and NMR are used on a
variety of alpha melanocyte-stimulating hormone (alpha-MSH) analogues to
understand the physical characteristics required for biological potency. Peptides
I (Ac-[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2), II (Ac-c[Nle4,Asp5,D
Phe7,Lys10]alpha-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4
10)-NH2 all show very similar conformational properties (backbone and side-chain
torsional angles), and all display high biological potencies. The modeling
results for these compounds are supported by the NMR data. Peptide IV (Ac
c[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4-10)-NH2) appears to have a markedly
different conformation and has decreased biological potency.
PMID- 9650717
TI - Lanthionine macrocyclization by in situ activation of serine.
AB - The present report details a straightforward, solid-phase approach to
cyclolanthionine peptides. After stepwise assembly of the linear sequence and
transformation of a single exposed serine to bromoalanine using P(Ph)3/CBr4, the
detritilation of a cysteine side-chain sets the stage for a base-promoted
macrocyclization. The entire procedure can be carried out in a solid-phase vessel
using conventional 9-fluorenylmethyloxycarbonyl/tert-butyl-based chemistry and is
amenable to automated format. The utility of this novel procedure is demonstrated
by the synthesis of two previously reported lanthionine-containing cyclic
peptides.
PMID- 9650718
TI - Characterization of the thiol/disulfide chemistry of peptides corresponding to
the 603-609 disulfide loop of the human immunodeficiency virus (HIV) envelope
glycoprotein gp41.
AB - The redox chemistry of two synthetic model peptides for the 603-609 disulfide
loop found in envelope glycoprotein gp41 of the human immunodeficiency virus type
1 (HIV-1) are reported. The two peptides: N-Ac-Trp-Gly-Cys-Ser-Gly-Lys-Leu-Ile
Cys-Thr-Thr-NH2 (I) and N-Ac-Trp-Gly-Cys-Ser-Gly-Arg-His-Ile-Cys-Thr-Thr-NH2 (II)
were synthesized by the solid phase method. Peptide I corresponds to amino acids
601-611 of gp41 of the North American/European strain of HIV-1. Peptide II
incorporates amino acid replacements frequent in African HIV-1 isolates. The
redox chemistry of the disulfide bonds in the two peptides was characterized in
aqueous and aqueous/urea solution by studying their thiol-disulfide exchange
reactions with the tripeptide glutathione (GSH). GSH reacts with the disulfide
bonds to form mixed disulfides, which in turn react with another molecule of GSH
to give the dithiol form of the peptide and GSSG. Equilibrium constants were
determined for each step and for the overall reduction reactions. Redox
potentials of -0.246V and -0.241V were calculated from the equilibrium constants
for the disulfide bonds in peptides I and II in aqueous solution at 25 degrees C
and pH 7.0. The overall equilibrium constants are less in 8 M urea solution,
which indicates a stabilization of the reduced, dithiol form of both peptides by
secondary structure which can be denatured by urea. This conclusion is supported
by nuclear Overhauser enhancement data obtained from 2D-ROESY NMR spectra which
provide evidence of elements of secondary structure for the reduced forms of both
peptides. The results are discussed in terms of a protein disulfide isomerase
catalyzed reduction of the disulfide bond in gp41.
PMID- 9650720
TI - A comparative conformational analysis of thimet oligopeptidase (EC 3.4.24.15)
substrates.
AB - The specificity of thimet oligopeptidase (EC 3.4.24.15) (TOP 24.15) does not
agree with theoretical models devised to explain the specificity characteristic
of peptidases toward certain sequences of amino acid residues. According to
previous studies peptide chains hydrolyzed by TOP 24.15 adopt similar main chain
conformations, although with different and in some cases small probabilities of
occurrence in aqueous solution. To determine specific structural features
recognized by TOP 24.15, a conformational search including eight polypeptides
with known susceptibilities for catalytic hydrolysis was executed and the
distribution of each main chain conformation found in the search was tabulated.
Two sets of main chain conformations were selected, those common to all peptides
in the study and those common only to substrates of TOP 24.15. The former set is
very small and includes mainly extended conformations. In contrast, the latter
set is large and its conformations are coiled and exhibit sharp turns coincident
with positions of hydrolysis by TOP 24.15. These results indicate a possible
basis for the selectivity of TOP 24.15.
PMID- 9650719
TI - Analysis of synthetic peptides by capillary zone electrophoresis in
organic/aqueous buffers.
AB - Whereas synthetic peptides have been routinely analyzed for purity by reverse
phase high performance liquid chromatography (RPHPLC) for a number of years, it
is only in the last decade that the use of capillary zone electrophoresis (CZE)
in aqueous buffers has been taken advantage of as an orthogonal method for the
detection of impurities. However, we have found that hydrophobic amino acids and
peptides often migrate as very broad, tailing absorbances or even precipitate in
the aqueous buffers during CZE analysis. As a result, alternative buffer systems
containing organic modifiers were sought. Varying concentrations of acetonitrile,
methanol and isopropanol in sodium phosphate and triethylammonium phosphate
buffers were used to study their effects on the electrophoretic migration of
several synthetic peptides [gonadotropin releasing hormone (GnRH), corticotropin
releasing factor (CRF) and analogs] and an enantiomeric synthetic amino acid. The
organic/aqueous buffers used to obtain the best conditions for separation of
porcine gonadotropin-releasing hormone (GnRH) and chicken II GnRH were then used
to optimize a separation of nine native forms of GnRH decapeptides.
Interestingly, several of these GnRHs have identical formal charges and yet could
be separated. This suggests a mixed mechanism of separation that discriminates
not only on the basis of peptide charge and structure but also of adsorptive
properties (Van der Waals forces, dipole-dipole interactions and hydrogen
bonding) of the capillaries.
PMID- 9650721
TI - Structure of cyclic peptides: the crystal and solution conformation of cyclo(Phe
Phe-Aib-Leu-Pro).
AB - A solid-state and solution conformation analyses of the cyclopentapeptide
cyclo(Phe-Phe-Aib-Leu-Pro) has been carried out by X-ray diffraction and nuclear
magnetic resonance techniques. The structure of the hexagonal crystals, grown
from a methanol solution [a = b = 16.530(4) A, c = 21.356(9) A, space group
P6(5), Z = 6], shows the presence of one intramolecular N-H ..O=C hydrogen bond
with the formation of a gamma-turn (C7). The Aib3 residue, at the center of the
gamma-turn, presents unexpected values of the torsion angles [phi = 70.5 degrees
and psi = -73.8 degrees], which have been observed only once before for this
helicogenic residue. A cis peptide bond occurs between Leu4 and Pro5; all other
peptide bonds are trans. The overall conformation for the cyclopentapeptide with
one cis-peptide bond on one side and an intramolecular gamma-turn on the opposite
side results in an equatorial topology of the side-chains of the Phe1, Phe2 and
Leu4 residues. Indeed, the Calpha-Cbeta and Cbeta-Cgamma bonds of these residues
lie approximately in the mean plane of the cyclic ring system. The structure is
compared with data in the literature on cyclic pentapeptides. In addition the Pro
Phe-Phe moiety shows a conformation similar to that observed in other larger
cyclic bioactive peptides, which indicates a reduced number of conformations for
this sequence. The solution study was carried out in three different solvent
systems: chloroform, acetonitrile and methanol in the temperature interval 220
300 K. In all three solvents the room temperature spectra show that the peptide
is conformationally nonhomogeneous. In acetonitrile at low temperatures it is
possible to reduce the conformational equilibrium to two predominant conformers
which differ for the cis-trans isomerism of the Leu4-Pro5 peptide bond.
PMID- 9650722
TI - Soil forming and plant density effects on carrot yield and internal quality.
AB - The effects of soil forming (SF) and plant density (PD) on the carrot yield, mean
root weight and internal quality was studied in field experiments in 1993 and
1994. 'Fontana BZ' carrots were grown in flat land, a narrow ridge, a broad
ridge, and a compacted broad ridge soil configurations with low (LD) and high
(HD) target plant densities, four and seven hundred thousand carrots per hectar.
The total and marketable yields were larger in flat land and narrow ridge than in
the broad- and compacted broad ridges in 1993 and in 1994 at HD. The number of
marketable carrots were highest with the flat land soil configurations in both
years. A dry spring in 1993 favored flat land growing conditions; in ridges the
fine sand dried quickly. SF did not influence the mean weight of a marketable
carrot in 1993, but in 1994 the narrow ridge configuration resulted in heavier
carrots than the flat land or broad ridge growing conditions. In the climatically
more unfavorable year of 1993, SF and PD affected quality; dry matter was lower
in flat land than in the ridges. At HD, the flat land soil configuration produced
higher glucose and fructose than carrots grown in the narrow and broad ridges.
Dietary fiber and vitamin C were higher in narrow ridge than in compacted broad
ridge grown carrots. At LD the flat land and broad ridge produced highest and
compacted broad ridge the lowest beta-carotene contents; alpha-carotene was
higher at LD than at HD.
PMID- 9650723
TI - Mineral binding capacity of dephytinized insoluble fiber from extruded wheat, oat
and rice brans.
AB - Insoluble fiber fractions from raw and extruded oat, rice and wheat brans were
isolated and phytate removed. In vitro mineral binding studies were performed
utilizing copper (Cu2+), calcium (Ca2+) and zinc (Zn2+) ions, which were added
individually to enzymatically treated (Prosky et al., 1985), acid washed
insoluble fiber residues from oat, rice and wheat brans. The enzymatic digestion
step with alpha-amylase, protease and amyloglucosidase served to remove protein
and starch from the samples. Mineral binding studies were performed on the
insoluble fiber residue. Mineral content was determined by flame atomic
absorption spectroscopy. Raw brans served as controls. A twin-screw extruder
Model DNDG-62/20D, manufactured by Buhlerag (CH-9240, Uzwil, Switzerland) was
utilized. The objectives of the study were to determine the total Cu2+, Ca2+ and
Zn2+ binding capacity of the dephytinized insoluble fiber from each bran; and to
determine if extrusion screw speed affected the brans' insoluble fiber mineral
binding capacity. Although dephytinized, the brans' insoluble fiber fraction
bound Cu2+, Ca2+ and Zn2+ ions. Oat bran bound more Cu2+, Ca2+ and Zn2+ than
wheat bran, which bound more than rice bran. Extrusion processing did not affect
the brans' insoluble fiber binding capacity to bind Cu2+. However, it increased
the binding capacity of Ca2+ and Zn2+ of the insoluble fiber fraction from rice
and oat brans.
PMID- 9650724
TI - Evaluation of growth of Neosartorya spp. on some Nigerian fruit products.
AB - Growth of Neosartorya fischeri, N. fischeri var. spinosa and N. quadricincta on
inoculated fruit juice agars (FJAs) consisting of 1% agar and juices from mango
(MJA), orange (OJA) and pineapple (PJA) containing various levels of added
sucrose was studied in terms of the average number of colonies produced by their
ascospores, time (days) required before colonies were formed and developed to
confluent mycelial mat as well as the level of reproductive spores produced. The
means of the number of colonies on PJA and OJA without added sucrose were
significantly (p = 0.05) higher than that of MJA. Addition of sucrose at levels
of 10% to PJA, 11.5% to OJA and 9% to MJA increased the numbers of colonies
whereas sucrose levels of 30% or more in PJA, 31.5% or more in OJA and 29% or
more in MJA decreased the number of colonies produced. At any level of added
sucrose to FJAs, a significant (p = 0.05) delay occurred before the colonies were
formed and developed to confluent mycelial mat except in PJA containing 10%
sucrose. All cultures produced abundant cleistothecia on all FJAs without added
sucrose. Addition of sucrose at levels of 30% to PJA, 31.5% to OJA and 29% to MJA
resulted in the production of abundant conidial heads with a corresponding
decrease in the proportion of cleistothecia.
PMID- 9650725
TI - Hypolipidemic effect of flavonoids from Solanum melongena.
AB - Flavonoids extracted from the fruits of Solanum melongena (Brinjal) orally
administered at a dose of 1 mg/100 g BW/day showed significant hypolipidemic
action in normal and cholesterol fed rats. HMG CoA reductase activity was found
to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate
dehydrogenase were significantly reduced. Activities of lipoprotein lipase and
plasma LCAT showed significant enhancement. A significant increase in the
concentrations of hepatic and fecal bile acids and fecal neutral sterols was also
observed indicating a higher rate of degradation of cholesterol.
PMID- 9650726
TI - Composition and functional properties of protein isolates obtained from
commercial legumes grown in northern Spain.
AB - Pea (Pisum sativum), faba bean (Vicia faba) and soybean (Glycine max) seeds were
characterized, and protein isolates were prepared following an isoelectric point
precipitation procedure. Soybean seeds showed the highest protein content (36.7%)
and carbohydrate was the major constituent in the pea (59.4%) and the faba bean
seeds (52.1%). Protein contents were higher than 80% in all the protein isolates.
The amino acid contents in the protein isolates were, in general, higher than
those in their own starting seeds. The antinutritional factor contents were
reduced after the protein isolate preparation. The highest reductions achieved
for tannins were 95% in the faba bean protein isolate, and for phytates (45%) and
trypsin inhibitor activity (46%) in the pea protein isolate. Haemagglutinating
activity was not detected in any of the protein isolates. Minimum solubility
values were observed at a pH range between 4.0 and 6.0, and maximal solubilities
were obtained at basic pH values. The faba bean protein isolate showed the
highest water and oil absorption capacities, and the best gelling properties. The
soybean protein isolate had the best foam expansion capacity. Thus, the protein
isolates had an improvement in some of the characteristics compared to their
original seeds with lower contents in tannins, phytates and haemagglutinating
activity, but had weak functional properties.
PMID- 9650727
TI - Cultivar and processing effects on the pasting characteristics, tannin content
and protein quality and digestibility of cowpea (Vigna unguiculata).
AB - Four popular West African local cultivars of cowpea (Vigna unguiculata), with
distinctly different seed coat colors, were evaluated for their relative
amylograph pasting characteristics, condensed tannin content, in vitro protein
digestibility and Tetrahymena protein efficiency ratio (t-PER). The effects of
roasting and dehulling on these properties were also determined. There were wide
variations in the hot paste viscosity characteristics of the different cultivars
studied. The raw cowpea flour samples exhibited maximum paste viscosities ranging
between 260 Brabender Units (BU) for the Mottled cultivar and 460 BU for the
cream-colored Blackeye cultivar. Cowpea cultivars with the greatest peak
viscosities showed low stabilities to extended cooking. Roasting depressed paste
viscosity properties of all the cowpea cultivars studied. Tannin concentrations
were 0.3-6.9 and 7.2-116 mg CE/g flour from whole cowpea seeds and seed coats
respectively, increasing with intensity of seed color. Although dehulling removed
98% of the tannin content of raw cowpeas, improvement in protein quality as a
result of dehulling was observed for only the highly-pigmented Maroon-red
variety. Roasting significantly improved digestibility and more than doubled the
t-PER of all cowpea cultivars studied. Roasted cowpeas possess adequate
nutritional and functional qualities as protein supplements in cereal-based
weaning foods. However, it appears that dehulling is necessary to enhance the
nutritional quality of the highly pigmented cultivars of cowpea.
PMID- 9650728
TI - Effect of spraying selected pesticides on the contents of specified minerals in
cabbage.
AB - The present study was conducted to assess the effect of spraying of pesticides on
the content of minerals in cabbage harvested at varying waiting periods (0, 7, 14
and 21 days) after spraying. The amounts of phosphorus and zinc in cabbage were
significantly (p < 0.05) decreased while those of iron, calcium and potassium
were significantly (p < 0.05) increased by the sprayings of pesticides. At
varying waiting periods after the spraying of pesticides calcium, phosphorus,
zinc and potassium contents of cabbage were found to be decreased remarkably (p <
0.05) while the content of iron was increased significantly (p < 0.05). Between
the two pesticides, the spraying of endosulfan exerted a more pronounced effect
in altering the contents of minerals than the spraying of malathion.
PMID- 9650729
TI - Effect of soy-fortification method on the fermentation characteristics and
nutritional quality of fermented maize meal.
AB - Studies were conducted to develop an appropriate household/small-scale enterprise
level technique for the production of soy-fortified fermented maize dough (or
meal) by comparing different treatments, processing methods and fortification
levels. The effects of fortification method of the Ghanaian traditional fermented
maize dough with raw or heat-treated whole soybeans and full-fat soyflour at 0%,
10% and 20% replacement levels, on the rate of fermentation and product quality
were investigated. Sensory characteristics, trypsin inhibitor activity, amino
acid pattern, proximate composition and hot paste viscosity were used as the
indices of quality. Addition of whole soybeans to maize before milling and
fermentation reduced the fermentation time by 60% while increasing the protein
content by 24% and 70% respectively for 10% and 20% levels of fortification. A
significant improvement was also achieved in the amino acids pattern of the
fortified dough. However, raw whole soybeans imparted an undesirable color and
beany flavor and an appreciable concentration of trypsin inhibitor activity (TIA)
to the dough. Boiling soybeans for 20 min before incorporation into the maize for
milling and fermentation was found necessary for desirable flavor and low levels
of TIA. Little or no changes in the pasting viscosity characteristics occurred in
samples containing boiled soybeans, while the usual method of fortifying maize
meal with soy flour was found to severely depress the pasting viscosity
characteristics and drastically reduced the acidity of the fermented dough. Based
on the findings of the study, the most appropriate technique for the production
of soy-fortified high protein fermented maize dough has been suggested to involve
incorporation of boiled whole soybeans in soaked maize before milling and
fermentation for improved sensory characteristics, enhanced nutritive value and
optimal functional properties.
PMID- 9650730
TI - Energy cost and running mechanics during a treadmill run to voluntary exhaustion
in humans.
AB - The aim of the present study was to examine the physiological and mechanical
factors which may be concerned in the increase in energy cost during running in a
fatigued state. A group of 15 trained triathletes ran on a treadmill at
velocities corresponding to their personal records over 3000m [mean 4.53 (SD
0.28) m x s(-1)] until they felt exhausted. The energy cost of running (CR) was
quantified from the net O2 uptake and the elevation of blood lactate
concentration. Gas exchange was measured over 1 min firstly during the 3rd-4th
min and secondly during the last minute of the run. Blood samples were collected
before and after the completion of the run. Mechanical changes of the centre of
mass were quantified using a kinematic arm. A significant mean increase [6.9 (SD
3.5)%, P < 0.001] in CR from a mean of 4.4 (SD 0.4) J x kg(-1) x m(-1) to a mean
of 4.7 (SD 0.4) J x kg(-1) x m(-1) was observed. The increase in the O2 demand of
the respiratory muscles estimated from the increase in ventilation accounted for
a considerable proportion [mean 25.2 (SD 10.4)%] of the increase in CR. A mean
increase [17.0 (SD 26.0)%, P < 0.05] in the mechanical cost (CM) from a mean of
2.36 (SD 0.23) J x kg m(-1) to a mean of 2.74 (SD 0.55) J x kg(-1) x m(-1) was
also noted. A significant correlation was found between CR and CM in the non
fatigued state (r=0.68, P < 0.01), but not in the fatigued state (r=0.25, NS).
Furthermore, no correlations were found between the changes (from non-fatigued to
fatigued state) in CR and the changes in CM suggesting that the increase in CR is
not solely dependent on the external work done per unit of distance. Since step
frequency decreased slightly in the fatigued state, the internal work would have
tended to decrease slightly which would not be compatible with an increase in CR.
A stepwise regressions showed that the changes in CR were linked (r=0.77, P <
0.01) to the changes in the variability of step frequency and in the variability
of potential cost suggesting that a large proportion of the increase in CR was
due to an increase in the step variability. The underlying mechanisms of the
relationship between CR and step variability remains unclear.
PMID- 9650731
TI - Physiological and performance responses to supplementation with thiamin and
pantothenic acid derivatives.
AB - The purpose of this study was to investigate the physiological and performance
responses to supplementation with allithiamin and pantethine. On two separate
occasions, six highly trained cyclists [maximum O2 consumption or VO2max 61.8
(2.1) ml x kg(-1) x min(-1)] performed a 50-km steady-state ride on a cycle
ergometer at a workload corresponding to approximately 60% of VO2max followed by
a 2000-m time trial. For 7 days prior to each ride, subjects daily ingested
either a placebo (PL) or a combination of 1 g of allithiamin and 1.8 g of a
55%/45% pantethine/pantothenic acid compound (AP). Treatments were administered
using a randomized, double-blind, counter-balanced design. During the 50km ride,
measures of heart rate, respiratory gas exchange and ratings of perceived
exertion were recorded at 5, 15, 25, 35 and 45 km. Blood samples were collected
at 10, 20, 30, 40 and 50 km and analyzed for lactate, glucose and free fatty
acids. Blood samples for the analysis of lactate were also collected 3 and 5 min
after the completion of the 2000-m time trial. There were no significant
differences in any of the measured parameters between experimental conditions.
Time to complete the 2000-m time trial was also not significantly different
between experimental conditions [PL 178.2 (8.4), AP 170.7 (10.2) s; P=0.58].
These results suggest that, despite the reported enhanced absorption properties,
supplementation with allithiamin and pantethine does not alter exercise
metabolism or exercise performance.
PMID- 9650732
TI - The mathematics of breaking away and chasing in cycling.
AB - In cycling stage races a small group of riders will often form a "breakaway" and
establish a lead over the main group. This paper examines the factors that affect
the likelihood of success for the breakaway. A mathematical approach is used,
drawing on a model of cycling previously developed and validated (Olds et al. J
Appl Physiol 78:1596 1611, 1995). In a breakaway group, the power required to
overcome air resistance is reduced because the lead can be shared, with trailing
riders sheltering or drafting behind leading riders. The benefit of drafting can
be quantified as a function of the distance between riders using previously
obtained data. Of course, this advantage is even greater in the (larger) chasing
group, so that eventually the chasing group will catch the breakaway, assuming
identical bicycles and physiological characteristics. The question addressed is:
what factors determine how great a lead the breakaway must have in order for the
chasing group to be unable to catch the breakaway before the finish of the race?
Demand-side simulations show that the critical factors are: the distance
remaining in the race; the speed of the breakaway group; the number of riders in
the chasing and breakaway groups: how closely riders in each group draft one
another; the grade; surface roughness; as well as head- and cross-winds. When
supply-side physiological factors are incorporated, the maximum sustainable speed
and maximum lead time can be calculated.
PMID- 9650733
TI - Electron spin resonance spectroscopic detection of oxygen-centred radicals in
human serum following exhaustive exercise.
AB - Free radicals or oxidants are continuously produced in the body as a consequence
of normal energy metabolism. The concentration of free radicals, together with
lipid peroxidation, increases in some tissues as a physiological response to
exercise - they have also been implicated in a variety of pathologies. The
biochemical measurement of free radicals has relied in the main on the indirect
assay of oxidative stress by-products. This study presents the first use of
electron spin resonance (ESR) spectroscopy in conjunction with the spin-trapping
technique, to measure directly the production of radical species in the venous
blood of healthy human volunteers pre- and post-exhaustive aerobic exercise.
Evidence is also presented of increased lipid peroxidation and total antioxidant
capacity post-exercise.
PMID- 9650734
TI - Effects of in vivo-like activation frequency on the length-dependent force
generation of skeletal muscle fibre bundles.
AB - It is known that a range of firing frequencies can be observed during in vivo
muscle activity, yet information is lacking as to how different in vivo-like
frequencies may affect force generation of skeletal muscle. This study examined
the effects of constant (CSF, constant within one contraction) and decreasing
stimulation frequencies (DSF) on mean sarcomere length-force characteristics of
rat gastrocnemius medialis fibre bundles. The CSF resulted in an optimal mean
sarcomere length (lso) of 2.30 (SEM 0.02), 2.46 (SEM 0.03), 2.76 (SEM 0.03) and
more than 2.99 (SEM 0.07) lm, for 100, 50, 30 and 15 Hz, respectively. Compared
to 100-Hz stimulation, both lso and the ascending limb of the relationship
significantly shifted to higher lengths with lower frequencies. No shift was
encountered for the initial part of the descending limb. The DSF reduced the
frequency-induced shift to higher mean lengths [lso 2.33 (SEM 0.02), 2.52 (SEM
0.08) and more than 2.92 (SEM 0.10) microm, respectively, for 50, 30 and 15 Hz].
No effect of activation time on length-force characteristics was observed. It was
concluded from these studies that the frequency and history of stimulation is a
major determinant of the length-force characteristics of muscle fibre bundles,
and should be taken into account when analysing animal and human locomotion. The
previously observed frequency-induced shift in whole muscle length-force
relationship resides mainly at the level of fibre bundles.
PMID- 9650735
TI - Heritability of running economy: a study made on twin brothers.
AB - Running economy (RE), defined as the steady-state of oxygen uptake (VO2) for a
given running velocity, is a factor of sports performance the genetic component
of which has seldom been reported to date. We studied this component using a
heritability index (HI) in a group of 32 male twins, 8 monozygotic (MZ) and 8
dizygotic (DZ) pairs, all sportsmen with similar perinatal and environmental
backgrounds. Zygocity was determined by the identity of erythrocytic antigenic,
protein and enzymatic polymorphism, and human leucocyte antigen serologic types
between co-twins. The subjects exercised twice on a treadmill, once until
exhaustion and again at submaximal intensities. Pulmonary gas exchange was
measured continuously using an automatic analyser system during both tests. Blood
samples were obtained during the recovery period to determine lactate
concentrations. No significant differences were observed between MZ and DZ, in
respect of RE at any speed or in maximal VO2 relative to body mass. Nevertheless,
significant HI (P < 0.05) was found in maximal lactate concentrations (HI=0.75)
and in respiratory equivalent for oxygen at two speeds, 7 km x h(-1) HI=0.71) and
8 km x h(-1) (HI=0.79), differences which probably suggest that there are
differences in RE. In conclusion, we did not detect a genetic component in RE or
in maximal oxygen uptake, but a genetic component for markers of anaerobic
metabolism was present.
PMID- 9650736
TI - Effect of restricted blood flow on exercise-induced hormone changes in healthy
men.
AB - To test the influence of the accumulation of metabolites on exercise-induced
hormone responses, plasma concentrations of cortisol, growth hormone (GH),
insulin, testosterone, thyrotropin (TSH), free thyroxine (fT4) and
triiodothyronine (T3) were compared during exercise performed under normal
conditions (control) and under conditions of restricted blood flow of exercising
leg muscles (ischaemia) in nine healthy young men. Blood supply was reduced by
15%-20% by the application of 50 mmHg external pressure over the exercising leg.
During 45-min cycling exercise during ischaemia the increase in GH concentration
was twice as large as under normal conditions. Despite the below-threshold
exercise intensity for activation of the pituitary-adrenocortical system under
normal exercise conditions ischaemic exercise elicited cortisol and T3 responses
(concentration increases of 83% and 9.5%, respectively). Ischaemic exercise
attenuated the decrease of plasma insulin concentration found under normal
conditions. The concentrations of testosterone, TSH and fT4 were not changed
significantly during exercise performed in either condition. The results support
the suggested essential role of muscle metaboreceptors in the control of hormone
responses during muscle activity.
PMID- 9650737
TI - Effects of beta-adrenoceptor-blockade on stress-induced adrenocorticotrophin
release in humans.
AB - We investigated the mechanisms of stress-induced alterations in
adrenocorticotrophin (ACTH) release. Tandem parachutists received either a
placebo or the beta-adrenoceptor antagonist propranolol prior to a first time
parachute jump. Blood samples were drawn 4 h before, immediately after, and 1 h
after the jump. Cortisol and catecholamine concentrations displayed a significant
stress-induced increase in both groups. The ACTH plasma concentrations
significantly increased in the placebo and the propranolol group, with
significantly more pronounced changes in the propranolol-treated subjects
compared to the placebo group. These data demonstrated a stress-induced increase
of ACTH plasma concentrations in humans that was enhanced by beta-blockade.
PMID- 9650738
TI - Summation of elementary phonomyograms during isometric twitches in humans.
AB - To study its summation principle, the phonomyogram (PMG) from the first
interosseus dorsalis muscle was recorded in five subjects during single twitches
evoked by electrical stimulation over the motor point. By increasing the current
pulse from threshold to maximal intensity, PMG amplitude increased linearly with
motor unit recruitment. The twitch amplitude-intensity relationship was also
linear. The PMG amplitude was therefore linearly related to the external force.
For all these relationships highly significant correlation coefficients were
found. These relationships were interpreted as being a consequence of an orderly
recruitment, although, contrary to what happens during voluntary contraction, the
largest and strongest motor units were recruited before the smallest and weakest
ones during axon electrical stimulation. The PMG onset always preceded twitch
onsets as indicated by latency measurements [mean 3.2 (SD 1.3) ms versus 11.5 (SD
3.9) ms, respectively]. Moreover, PMG and twitch latencies may have been
significantly reduced by recruitment, suggesting that orderly recruitment
influenced both PMG amplitude and occurrence. These results were interpreted as
being the result of the summation of elementary PMG from every contracting motor
unit and the stiffness change of the muscle medium occurring with recruitment.
PMID- 9650739
TI - The influence of either no fluid or carbohydrate-electrolyte fluid ingestion and
the environment (thermoneutral versus hot and humid) on running economy after
prolonged, high-intensity exercise.
AB - This study investigated the effects on running economy (RE) of ingesting either
no fluid or an electrolyte solution with or without 6% carbohydrate
(counterbalanced design) during 60-min running bouts at 80% maximal oxygen
consumption (VO2max). Tests were undertaken in either a thermoneutral (22-23
degrees C; 56-62% relative humidity, RH) or a hot and humid natural environment
(Singapore: 25-35 degrees C; 66-77% RH). The subjects were 15 young adult male
Singaporeans [VO2max=55.5 (4.4 SD) ml kg(-1) min(-1)]. The RE was measured at 3 m
s(-1) [65 (6)% VO2max] before (RE1) and after each prolonged run (RE2). Fluids
were administered every 2 min, at an individual rate determined from prior tests,
to maintain body mass (group mean=17.4 ml min(-1)). The VO2 during RE2 was higher
(P < 0.05) than that during the RE1 test for all treatments, with no differences
between treatments (ANOVA). The mean increase in VO2 from RE1 to RE2 ranged from
3.4 to 4.7 ml kg(-1) min(-1) across treatments. In conclusion, the deterioration
in RE at 3 m s(-1) (65% VO2max) after 60 min of running at 80% VO2max appears to
occur independently of whether fluid is ingested and regardless of whether the
fluid contains carbohydrates or electrolytes, in both a thermoneutral and in a
hot, humid environment.
PMID- 9650740
TI - The effect of severe eccentric exercise-induced muscle damage on plasma elastase,
glutamine and zinc concentrations.
AB - The aim of this study was to determine if severe exercise-induced muscle damage
alters the plasma concentrations of glutamine and zinc. Changes in plasma
concentrations of glutamine, zinc and polymorphonuclear elastase (an index of
phagocytic cell activation) were examined for up to 10 days following eccentric
exercise of the knee extensors of one leg in eight untrained subjects. The
exercise bout consisted of 20 repetitions of electrically stimulated eccentric
muscle actions on an isokinetic dynamometer. Subjects experienced severe muscle
soreness and large increases in plasma creatine kinase activity indicative of
muscle fibre damage. Peak soreness occurred at 2 days post-exercise and peak
creatine kinase activity [21714 (6416) U x l(-1) mean (SEM)] occurred at 3 days
post-exercise (P < 0.01 compared with pre-exercise). Plasma elastase
concentration was increased at 3 days post-exercise compared with pre-exercise (P
< 0.05), and is presumably indicative of ongoing phagocytic leucocyte
infiltration and activation in the damaged muscles. There were no significant
changes in plasma zinc and glutamine concentrations in the days following
eccentric exercise. We conclude that exercise-induced muscle damage does not
produce changes in plasma glutamine or zinc concentrations despite evidence of
phagocytic neutrophil activation.
PMID- 9650741
TI - Effects of arm and leg loading on sprint performance.
AB - The effects of loading on sprint kinematics were examined in 24 male students.
The moment of inertia of either the arms or legs was increased by up to 50% of
their unloaded values and the time for distances of 0.5-15 m and 15-30 m from a
sprint start was measured. An increase in leg loading was associated with a
gradual decrease in velocity of both sprint phases, while the change associated
with arm loading was modest and significant only in the second phase. The
decrease in sprint velocity was predominantly due to a reduction in stride rate,
while the stride length remained almost unchanged. It was concluded that leg
loading affected sprint velocity more than arm loading, and also that the
velocity was reduced due to a decrease in the stride rate rather than in the
stride length.
PMID- 9650742
TI - Oxygen uptake during moderate intensity running: response following a single bout
of interval training.
AB - Eight male endurance runners [mean+/-(SD): age 25 (6) years; height 1.79 (0.06)
m; body mass 70.5 (6.0) kg; % body fat 12.5 (3.2); maximal oxygen consumption
(VO2max 62.9 (1.7) ml x kg(-1) x min(-1)] performed an interval training session,
preceded immediately by test 1, followed after 1 h by test 2, and after 72 h by
test 3. The training session was six 800-m intervals at 1 km x h(-1) below the
velocity achieved at VO2max with 3 min of recovery between each interval. Tests
1, 2 and 3 were identical, and included collection of expired gas, measurement of
ventilatory frequency (fr), heart rate (Fc)r rate of perceived exertion (RPE),
and blood lactate concentration ([La-]B) during the final 5 min of 15 min of
running at 50% of the velocity achieved at V02max (50% v-VO2max). Oxygen uptake
(VO2), ventilation (VE), and respiratory exchange ratio (R) were subsequently
determined from duplicate expired gas collections. Body mass and plasma volume
changes were measured preceding and immediately following the training session,
and before tests 1-3. Subjects ingested water immediately following the training
session, the volume of which was determined from the loss of body mass during the
session. Repeated measures analysis of variance with multiple comparison (Tukey)
was used to test differences between results. No significant differences in body
mass or plasma volume existed between the three test stages, indicating that the
differences recorded for the measured parameters could not be attributed to
changes in body mass or plasma volume between tests, and that rehydration after
the interval training session was successful. A significant (P < 0.05) increase
was found from test 1 to test 2 [mean (SD)] for VO2 [2.128 (0.147) to 2.200
(0.140) l x min(-1)], fc [125 (17) to 132 (16) beats x min(-1)], and RPE [9 (2)
to 11 (2)]. A significant (P < 0.05) decrease was found for submaximal R [0.89
(0.03) to 0.85 (0.04)]. These results suggest that alterations in VO2 during
moderate-intensity, constant-velocity running do occur following heavy-intensity
endurance running training, and that this is due to factors in addition to
changed substrate metabolism towards greater fat utilisation, which could explain
only 31% of the increase in VO2.
PMID- 9650743
TI - Significant changes in VLDL-triacylglycerol and glucose tolerance in obese
subjects following ten days of training.
AB - We characterized the effect of ten days of training on lipid metabolism in 6 [age
37.2 (2.3) years] sedentary, obese [BMI 34.4 (3.0) kg x m(-2)] males with normal
glucose tolerance. An oral glucose tolerance test was performed prior to and at
the end of the 10 d of training period. The duration of each daily exercise
session was 40 min at an intensity equivalent to approximately 75% of the age
predicted maximum heart rate. Blood measurements were performed after an
overnight fast, before and at the end of the 10 d period. Plasma triacylglycerol
was significantly (p < 0.05) reduced following exercise training (2.15+/-0.29 vs.
1.55+/-0.28 mmol x l(-1)). Very low density lipoprotein-triacylglycerol was also
significantly (p < 0.05) reduced (1.82+/-0.3 vs. 1.29+/-0.29 mmol x l(-1)). No
significant changes in high density lipoprotein-cholesterol were observed as a
result of training. Following training fasting plasma glucose and fasting plasma
insulin were significantly reduced [Glucose: 5.9 (0.2) mmol x l(-1) vs. 5.3
(0.22) mmol x l(-1) (p < 0.05); Insulin 264.3 (53.8) rho x mol x l(-1) vs. 200.9
(30.1) rho x mol x l(-1), p=0.05]. The total area under the glucose curve during
the OGTT decreased significantly (p < 0.05). These preliminary data suggest that
short-term exercise, without concomitant loss of body mass, induces favorable
changes in plasma triacylglycerol, and very low density lipoprotein
triacylglycerol and glucose tolerance but has no effect on high density
lipoprotein-cholesterol.
PMID- 9650744
TI - Prolonged intermittent high intensity exercise impairs neuromuscular performance
of the knee flexors.
AB - This study investigated the effect of prolonged intermittent high intensity
exercise upon the isokinetic leg strength and electromechanical delay of the knee
flexors. Seven male collegiate soccer players were exposed to: (i) a prolonged
intermittent high intensity exercise task (PIHIET) which required subjects to
complete a single-leg pedalling task, with the preferred limb, (75 rpm for all
constant-load portions of the task) consisting of 48 x 1.8 minute cycles of
exercise, and (ii) a control task consisting of no exercise. Pre-, mid- and post
PIHIET gravity corrected indices of knee flexion angle-specific torque (0.44 rad
knee flexion (AST); 0 rad=full knee extension; [1.05 rad x s(-1)]) were made for
both intervention and control limbs. Electromechanical delay (EMD) of the m.
biceps femoris during supine knee flexion movements was evaluated in the
preferred leg on both intervention and control days. Repeated measures ANOVAs
revealed significant condition (intervention; control) by time (pre; mid; post)
interactions for both knee flexor AST (F[2,12]=4.8; p < 0.03) and EMD
(F[2,12]=4.1; p < 0.05). AST was observed to decrease by 16% and EMD increase by
30% pre to post intervention. These observations suggest an impairment of
neuromuscular control and the ability to maintain force generation in the knee
flexors, near the extremes of the range of motion during prolonged intermittent
high-intensity exercise activities. Changes of this magnitude may pose a threat
to the integrity of the knee joint.
PMID- 9650745
TI - Advanced glycation end products co-localized with astrocytes and microglial cells
in Alzheimer's disease brain.
AB - In the previous study [Takeda et al. (1996) Neurosci Lett 221: 17-21], we
reported that the advanced glycation end products (AGEs) in the external space of
neuronal perikarya (extraneuroperikaryal AGE deposits) were significantly
abundant in the Alzheimer's brain. In this study, we investigated the spatial
relationship of the extraneuroperikaryal AGE (carboxymethyllysine and
pentosidine) deposits in astrocytes and microglial cells in the Alzheimer's
disease brain using double immunolabelling for AGEs and astrocyte or microglial
cell markers. Most of the extraneuroperikaryal AGE deposits were co-localized
with glial fibrillary acidic protein-positive astrocytes. AGE deposit-bearing
astrocytes also contained Gomori-positive granules. Furthermore, some of the
extraneuroperikaryal AGE deposits were co-localized with microglial cells. These
extraneuroperikaryal AGEs may activate astrocyte and microglia, and play a role
in pathogenesis of Alzheimer's disease.
PMID- 9650746
TI - p53 and PTEN gene mutations in gemistocytic astrocytomas.
AB - The gemistocytic astrocytoma is a histological variant of diffuse astrocytomas
and is characterised by the presence of large, GFAP-expressing neoplastic
astrocytes (gemistocytes) and a tendency towards rapid progression to
glioblastoma. In this study, we analyzed 28 gemistocytic astrocytomas (mean
fraction of gemistocytes, 35.0+/-9.9%) for mutations in the p53 and PTEN (MMAC1)
tumour suppressor genes. Single strand conformation polymorphism (SSCP), followed
by direct DNA sequencing of p53 exons 5-8, revealed a mutation in 23 of 28 (82%)
cases. Regional analysis of four tumours revealed identical p53 mutations in
gemistocytic and fibrillary tumour areas. In contrast, none of 15 gemistocytic
astrocytomas (WHO Grade II) and only two of 11 (18%) anaplastic gemistocytic
astrocytomas (WHO Grade III) contained a PTEN mutation. Of these, one was a 1 bp
deletion in codon 345 and the other a 1 bp insertion in intron 4. Differential
PCR did not reveal homozygous PTEN deletion in any of the tumours analysed. These
results indicate that p53 mutations are a genetic hallmark of gemistocytic
astrocytomas, whilst PTEN mutations are absent in low-grade and rare in
anaplastic gemistocytic astrocytomas.
PMID- 9650747
TI - Enhanced protein synthesis in the ipsilateral substantia nigra following middle
cerebral artery occlusion in the rat.
AB - Following focal cerebral ischemia, neuronal cell death is detected in remote
areas of the brain, including the ipsilateral thalamus and substantia nigra (SN),
as well as in the ischemic core. We have investigated protein synthesis in the
remote areas of rats exposed to focal ischemia using autoradiography. The
proximal portion of the left middle cerebral artery (MCA) was permanently
occluded, and at various periods (6 h, 2, 4 and 7 days and 2 and 4 weeks
following ischemia) animals received a single dose of L-[2,3-3H]valine (6.7
mCi/kg). Brain sections containing the thalamus and SN were processed for
autoradiography. In the ipsilateral cerebral cortex and striatum, marked
impairment of protein synthesis was observed and was never completely recovered
during the experiment. No changes in protein synthesis in the ipsilateral
thalamus were detected during the experiment. However, a change in protein
synthesis was demonstrated in the ipsilateral SN. At 2 days after MCA occlusion,
incorporation of [3H]valine into the whole zona reticulata of the ipsilateral SN
was slightly enhanced and the increase became evident at 4 days after ischemia.
Increased incorporation of [3H]valine began to be localized in the lateral
portion of the zona reticulata after 7 days and continued up to 4 weeks following
ischemia. Enhanced protein synthesis during the early stage (2 and 4 days after
ischemia) may be due to the activated function of the neurons in the zona
reticulata and that during the late stage (7 days and 2 and 4 weeks) after
ischemia to astroglial proliferation
PMID- 9650748
TI - Immunohistochemical study of clathrin in distal myopathy with rimmed vacuoles.
AB - Clathrin-coated vesicles are involved in three receptor-mediated intracellular
transport pathways: export from the Golgi apparatus, transfer of lysosomal
enzymes from the Golgi apparatus to lysosomes, and endocytosis at the plasma
membrane. Seeking evidence of transport abnormalities in distal myopathy with
rimmed vacuoles (DMRV), we performed immunohistochemistry for clathrin in muscle
biopsy specimens from patients with this disorder or other neuromuscular
disorders, and also in control muscle samples resected in orthopedic procedures.
While most myofibers from control muscle did not stain for clathrin, some fibers
revealed finely granular sarcoplasmic staining. In specimens from patients with
Duchenne and Becker muscular dystrophy, amyotrophic lateral sclerosis, peripheral
neuropathy, and DMRV, numerous clathrin-positive granules were often scattered
through the sarcoplasm and seen to a lesser extent in subsarcolemmal regions.
Quantitative immunohistochemical assessment showed more reactivity for clathrin
in DMRV than in controls and other diseased muscles, particularly in atrophic
fibers and type 2 fibers. Not all strongly clathrin-positive muscle fibers
contained rimmed vacuoles, although most fibers with vacuoles were clathrin
positive. The result suggests that the lysosome system is activated and receptor
mediated intracellular transport pathways function appropriately in the muscles
of DMRV patients.
PMID- 9650749
TI - Cortical Lewy bodies and Alzheimer-type changes in patients with Parkinson's
disease.
AB - We investigated the role of cortical Lewy bodies (LB) and Alzheimer-type changes
in cognitive impairment in patients with idiopathic Parkinson's disease (PD). We
evaluated 44 cases for the extent of neuropathological lesions with a CERAD
neuropathological assessment battery and the stage of dementia using Reisberg's
global deterioration scale (GDS). Substantia nigra, amygdala, hippocampus and
cerebral cortex were examined for LB and Alzheimer-type changes. For detection of
LB, the cortical areas were stained with polyclonal antibodies against ubiquitin
and tau. We found at least one cortical LB in 93% of cases. Furthermore, 43% of
the cases had histological findings of definite Alzheimer's disease (AD). The
association between cognitive impairment and the number of cortical LB and
Alzheimer-type changes in the amygdala, hippocampus and six selected gyri from
cerebral cortex were analyzed using stepwise linear regression. In this analysis
the total number of cortical LB, and the amount of neurofibrillary tangles in the
temporal cortex remained statistically significant. When the cases with
neuropathological changes consistent with a diagnosis of AD were excluded, the
correlation between the total number of cortical LB and cognitive impairment was
more obvious. A stepwise linear regression analysis in these cases found the
total number of cortical LB to be the statistically significant predictor of
cognitive impairment. This study revealed that LB densities in the cortex,
especially in the temporal neocortex, correlated significantly with the cognitive
impairment in PD independent of or in addition to Alzheimer-type pathology.
PMID- 9650750
TI - Phenytoin alters Purkinje cell axon morphology and targeting in vitro.
AB - In adult mice, administration of the anticonvulsive drug phenytoin caused focal
swellings along the Purkinje cell axon correlated with ataxia and incoordination
of movements. In our model, we used murine cerebellar slice cultures to study the
influence of phenytoin on postnatal Purkinje cell axon differentiation. Almost
all of our untreated cultures developed to mature-like cerebellar tissue.
Immunohistochemistry with anti-calbindin-D28k or UCHTI (anti-CD3) antibodies
revealed numerous Purkinje cell axons in the white matter. In the area of the
deep cerebellar nuclei, immunolabelled axons formed a large axonal plexus. The
few neurofilament-positive neurons in this area were densely covered with
Purkinje cell axon terminals. The synaptophysin immunoreactivity revealed
connections between the terminals and the neurons of the deep cerebellar nuclei.
Treatment of cerebellar slice cultures with phenytoin (10-80 microM) for 10-16
days resulted in focal swellings of different size along the axon. The number of
swellings increased with an increasing dosage. At concentrations of 40 microM
phenytoin, Purkinje cell axons seemed to be unable to invade the deep cerebellar
nuclei, but numerous aberrant, recurrent collaterals could be detected
immunohistochemically with the two specific Purkinje cell antibodies. Possible
cytotoxic effects after treatment, such as dendritic degeneration and a decrease
in the number of immunolabelled Purkinje cells, were observed above 40 microM
phenytoin. These data suggest that the response of juvenile Purkinje cells is
dependent upon the dosage of the antiepileptic drug because of morphological
alterations as well as a misrouting of previously established connections.
PMID- 9650751
TI - Neurotoxicity evoked by N-methyl-D-aspartate in the organotypic static slice
cultures of rat cerebral cortices: effect of GABA(A) receptor activation.
AB - We investigated the neurotoxicity evoked by N-methyl-D-aspartate (NMDA) receptor
stimulation in the organotypic static slice cultures of rat cerebral cortices. We
also examined whether the gamma-aminobutyric acid (GABA)A receptor agonist
muscimol has a protective effect on the NMDA-mediated neurotoxicity in this
culture system. NMDA-mediated cytotoxicity was evaluated histologically and
quantified by the measurement of lactate dehydrogenase (LDH) release into the
culture medium. There was an NMDA-induced, dose-dependent leakage of LDH release
and neuronal cell death, which were not attenuated by muscimol treatment. The
results suggested that NMDA neurotoxicity is reproduced in the organotypic
culture, and that GABA(A) receptor activation exerted no protective action
against the NMDA cytotoxicity.
PMID- 9650752
TI - Expression of low-affinity neurotrophin receptor p75NTR in the peripheral nervous
system of human neuropathies.
AB - Expression of low-affinity neurotrophin receptor (p75NTR) was
immunohistochemically examined in the peripheral nerve trunks, dorsal root
ganglia, sympathetic nerve ganglia and spinal cords in various human neurological
diseases manifesting peripheral neuropathies. p75NTR was expressed in the nerves
with axonal degeneration, and was also prominent in the nerves with newly
regenerating axons. In contrast, axonal pathology tended to reduce the expression
of p75NTR in the neuronal perikarya of the dorsal root ganglion and sympathetic
nerve ganglion neurons. In the ventral and lateral horn cells, the p75NTR
immunoreactivity was not detected in the normal and diseased nerves except for
amyloid polyneuropathy. These p75NTR expressions in the diseased human peripheral
nervous tissues would be regulated by an underlying pathology-related process,
and could play a role in peripheral nerve repair.
PMID- 9650753
TI - Mapping immunoreactive epitopes in the human peripheral nervous system using
human monoclonal anti-GM1 ganglioside antibodies.
AB - A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from
peripheral blood lymphocytes of patients with multifocal motor neuropathy and
Guillain-Barre syndrome. In solid-phase immunoassay, the antibodies react with
GMI, and also in differing degrees to the structurally related glycolipids asialo
GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM I
antibodies to epitopes within the human nervous system. Antibodies were observed
to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots,
dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and
skeletal muscle. The distribution of immunoreactive epitopes, which included
sensory structures, extended beyond those sites conventionally regarded as
pathologically affected in anti-GM1 antibody-associated motor nerve syndromes.
This undermines a model of disease pathogenesis based solely on antigen
distribution. Factors other than the presence or absence of antigen, such as the
local ganglioside topography, antibody penetration into, and pathophysiological
vulnerability of a particular site may also influence the clinicopathological
outcome of anti-GM1 antibody-mediated autoimmune attack.
PMID- 9650754
TI - Expression of retinoblastoma gene product and p21 (WAF1/Cip 1) protein in
gliomas: correlations with proliferation markers, p53 expression and survival.
AB - Using immunohistochemistry we evaluated the expression of two negative regulators
of the cell cycle, the retinoblastoma gene product (pRb) and the WAF1/Cip1 gene
product (p21), in consecutive paraffin sections from 54 gliomas (49 astrocytomas
and 5 oligodendrogliomas) and related it to clinicopathological parameters,
proliferative fraction, p53 expression and survival. Survival analysis was
restricted to the group of diffuse astrocytomas (48 patients). pRb expression did
not correlate with histological type, grade or p53 expression, while a moderately
strong correlation existed between pRb expression and the percentages of
proliferating cell nuclear antigen (PCNA) and MIB-1-positive cells. In 30% of
cases we observed diminished pRb expression (i.e., a low pRb/Ki-67 ratio),
irrespective of grade or histological type. p21 protein was elevated in 50% of
cases, especially within the higher grades. The percentage of p21-positive cells
was not related to histological type or grade but correlated loosely with PCNA
and pRb expression. A p53-negative/p21-negative phenotype was characteristic of
oligodendrogliomas and low-grade astrocytomas, whereas the p53-positive/p21
positive, p53-positive/p21-negative and p53-negative/p21-positive phenotypes were
almost equally distributed among high-grade tumors. In survival analysis (either
univariate or multivariate) diminished pRb expression was not a statistically
significant prognostic indicator. In contrast, p21 expression emerged as an
important indicator of shortened disease-free survival, in both univariate and
multivariate analyses. Moreover, the double-positive p53/p21 phenotype tended to
be associated with a shorter overall survival. Our results suggest that Rb gene
deregulation does not significantly affect prognosis but p21 expression may play
an important role in disease-free survival of astrocytoma patients.
PMID- 9650755
TI - Axonal injury and the neuropathology of shaken baby syndrome.
AB - We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who
lacked skull fracture. Evidence of axonal injury was sought using
immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta
amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the
cerebral white matter of all cases of SBS but were also present in 6 of 7
children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen
axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP
positive axons were present in both groups in the midbrain and medulla. The
cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5
of 7 contained swollen axons within the white matter tracts; in 2
immunoreactivity was localized to spinal nerve roots; in all 7 there was a
predilection for staining at the glial head of the nerve root. Among cases of
HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical
cord white matter. We conclude that cerebral axonal injury is common in SBS, and
may be due in part to hypoxic/ischemic injury. Cervical cord injury is also
common, and cannot be attributed to HIE. These findings corroborate suggestions
that flexion-extension injury about the cervical spinal column may be important
in the pathogenesis of SBS.
PMID- 9650756
TI - Structural and functional changes in skeletal muscle in anorexia nervosa.
AB - Protein-energy malnutrition in anorexia nervosa is an under-recognised cause of
muscle dysfunction. To characterise the skeletal myopathy that occurs in patients
with severe anorexia nervosa, muscle function and structure were comprehensively
examined in eight young adult female patients with severe (40%) self-induced
weight loss. All of the patients showed impaired muscle function on strength and
exercise measurement. The maximum voluntary contraction force for the patient
group was significantly less than predicted values. Electromyography revealed
myopathy in five of the patients, four of whom also had electro-physiological
evidence of neuropathy. However, muscle biopsy specimens consistently showed
myopathic changes with severe type 2 fibre atrophy but with no evidence of
neuropathic changes. Ultrastructurally, there was separation and segmental loss
of myofibrils and most biopsy samples contained abundant glycogen granules; we
have previously reported that one of the most consistent biochemical
abnormalities in these patients is impaired ischaemic lactate responses to
forearm exercise. The result of severe protein-energy malnutrition on the musculo
skeletal system is a metabolic myopathy. Although the patients admitted to a
variety of abnormal dieting behaviours, such as over-exercising and self-induced
vomiting, no association was found between any of these and quantitative
histological changes in the muscle biopsy samples. It is recommended that
myopathy in anorexia nervosa be treated by instituting an appropriate refeeding
programme.
PMID- 9650757
TI - Tissue distribution of pathological lesions and Hu antigen expression in
paraneoplastic sensory neuronopathy.
AB - We investigated the distribution of lesions and Hu antigen expression in two
autopsied cases of anti-Hu antibody-positive paraneoplastic sensory neuronopathy
(carcinomatous subacute sensory neuropathy). Pathological changes in both
patients were limited to the primary sensory neurons, some of the sympathetic
ganglia and hippocampal regions. The lesions showed a multifocal distribution
that differed among the spinal segmental levels and in the individual dorsal root
ganglia as well as in the nerve fascicles. Western blot analysis of the patients'
serum revealed that Hu antigens were extensively and widely expressed throughout
the central nervous system, sensory and sympathetic ganglia and cancer cells, but
not in the non-neural visceral tissues. Reverse transcriptase-polymerase chain
reaction also showed that the Hu D, Hu C, Hel-N1 and Hel-N2 mRNAs were
extensively and widely expressed through the neural tissues and cancer cells, but
not in the visceral tissues. Thus, the distribution of antigen expression was
very different from that of the lesions. Taken together with the distribution of
lesions and Hu antigen expression, it is suggested that factors other than anti
Hu antibodies are also involved in the pathogenesis of this neuronopathy.
PMID- 9650758
TI - Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma.
AB - We report a case of a 15-year-old girl with new onset seizures, who had a mixed
dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right
parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1
and a high T2 signal on magnetic resonance imaging. Architecturally it was in
large part intracortical and multinodular, but also featured a leptomeningeal
component. The former corresponded to DNT, a proliferation of oligodendroglia
like cells (OLCs) arranged in nodules, as well as comprising a diffuse
internodular element featuring "floating neurons" in a mucoid matrix. The
leptomeningeal portion of the lesion was a ganglioglioma consisting of large
neurons and astrocytes in association with marked desmoplasia. Spatially, the two
components abutted one another but appeared distinct. Immunohistochemistry showed
the neurons of the ganglioglioma to be positive for class III beta-tubulin,
synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for
glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100
protein. This apparently mixed lesion suggests that a close histogenetic
relationship exists between DNT and ganglioglioma. We postulate that the
pluripotential progenitor cells residing in the subpial granular layer may have
given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our
knowledge, this is the first detailed histological, immunochemical and
ultrastructural report of a mixed DNT and ganglioglioma.
PMID- 9650759
TI - The fatal attraction of polyglutamine-containing proteins.
PMID- 9650760
TI - Detection and incidence of cryptic Y chromosome sequences in Turner syndrome
patients.
AB - The presence of Y chromosome sequences in Turner syndrome (TS) patients may
predispose them to gonadoblastoma formation with an estimated risk of 15-25%. The
aim of this study was to determine the presence and the incidence of cryptic Y
chromosome material in the genome of TS patients. The methodology involved a
combination of polymerase chain reaction (PCR) and nested PCR followed by
Southern blot analysis of three genes the sex determining region Y (SRY), testis
specific protein Y encoded (TSPY) and RNA binding motif protein (RBM) (previously
designated as YRRM) and nine additional STSs spanning all seven intervals of the
Y chromosome. The methodology has a high sensitivity as it detects one 46,XY cell
among 10(5) 46,XX cells. Reliability was ensured by taking several precautions to
avoid false positive results. We report the results of screening 50 TS patients
and the identification of cryptic Y chromosome material in 12 (24%) of them.
Karyotypes were divided in four groups: 5 (23.8%) patients out of the 21 TS
patients which have the 45,X karyotype (group A) also have cryptic Y sequences;
none (0%) of the 7 patients who have karyotypes with anomalies on one of the X
chromosomes have Y mosaicism (group B); 1 (6.3%) of the 16 patients with a mosaic
karyotype have Y material (group C); and 6 (100%) out of 6 patients with a
supernumerary marker chromosome (SMC) have Y chromosome sequences (group D). Nine
of the 12 patients positive for cryptic Y material were recalled for a repeat
study. Following new DNA extraction, molecular analysis was repeated and, in
conjunction with fluorescent in situ hybridization (FISH) analysis using the Y
centromeric specific probe Yc-2, confirmed the initial positive DNA findings.
This study used a reliable and sensitive methodology to identify the presence of
Y chromosome material in TS patients thus providing not only a better estimate of
a patient's risk in developing either gonadoblastoma or another form of gonadal
tumor but also the overall incidence of cryptic Y mosaicism.
PMID- 9650761
TI - Sex ratio and absence of uniparental disomy in spontaneous abortions with a
normal karyotype.
AB - A series of spontaneous abortions collected in the South Wales region over a
period of 18 months was karyotyped to identify those with a normal chromosome
complement. Microsatellite polymorphisms distributed throughout all autosomes
were typed by the polymerase chain reaction to determine the parental origin of
each autosome pair in karyotypically normal spontaneous abortions. In 35 cases
biparental inheritance of every autosome pair was demonstrated. The sex ratio of
the normal spontaneous abortions of proven biparental origin was 0.77, but this
was not significantly different from 1.00.
PMID- 9650762
TI - G2 repair in Nijmegen breakage syndrome: G2 duration and effect of caffeine and
cycloheximide in control and X-ray irradiated lymphocytes.
AB - Lymphocytes from a patient with the Nijmegen breakage syndrome (NBS/NBS) and his
parents (NBS/+) have been analyzed to identify possible disturbances in
chromosomal G2 repair. The study included the determination of G2 duration and
the analysis of the chromosomal aberration frequencies in lymphocytes
with/without caffeine and cyclohexemide (CHM) treatments during G2, under control
and X-irradiated conditions. Under control conditions, NBS/NBS lymphocytes showed
that the basal chromosomal damage as well as the damage detected in G2, with
caffeine treatment, and the G2 duration were higher than cells from an age
matched control. In X-irradiated NBS/NBS lymphocytes, the basal and G2 chromosome
aberration frequencies were higher than in the controls; however, no significant
differences in G2 duration were detected between these two type of cells. Under X
irradiated conditions, NBS/+ lymphocytes showed that while the level of
chromosomal damage in G2 and the duration of this cell cycle phase were similar
to the control cells, the frequency of unrepaired chromosomal lesions was higher
than in the control lymphocytes. No significant differences in chromosomal damage
and G2 duration were detected in NBS/+ lymphocytes compared to the control cells,
under control conditions. CHM treatment, which induces an increase in G2
duration, decreased the basal spontaneous and X-ray induced chromosome aberration
frequency in NBS/NBS and NBS/+ lymphocytes. These results suggest that NBS
lymphocytes might be affected by some disturbances in their ability to extend the
G2 duration, which may be influencing their DNA repair efficiency in this phase
of the cell cycle.
PMID- 9650764
TI - Discordant repeat size and phenotype in Kennedy syndrome.
AB - Previous reports in the literature have described correlation of increasing
repeat length with severity of the phenotype, in Kennedy syndrome. We describe
male siblings with different repeat lengths, with lack of expression of the
phenotype in the sibling with the longer repeat length. The phenotype was
identical to motor neurone disease. There is variability of expression in Kennedy
syndrome and repeat length even in siblings cannot be taken as a conclusive
indicator of severity. CAG repeat length cannot be used to predict the natural
history of Kennedy disease. The diagnosis of Kennedy syndrome should be
considered in male patients presenting with atypical motor neurone disease.
PMID- 9650763
TI - Photoanthropometric study of craniofacial traits in individuals with Prader-Willi
syndrome on short-term growth hormone therapy.
AB - An objective photoanthropometric method, useful for delineating craniofacial
characteristics, was performed on 20 individuals with Prader-Willi syndrome (PWS;
14 males and 6 females) under 12 years of age and on growth hormone therapy (e.g.
for 3-12 months) to determine the effects of therapy on craniofacial features in
PWS. Facial parameters were measured from strict frontal and profile photographic
35 mm slides and compared with other facial measurements from the same face (e.g.
palpebral fissure width to bizygomatic diameter). We studied 16
photoanthropometric craniofacial indices following previously established
protocols. Our photoanthropometric data on 20 PWS subjects meeting diagnostic
criteria further supported previous findings of a high midface, a broad interalar
distance, a prominent high chin and broad ears in PWS patients without growth
hormone therapy. In addition, while on growth hormone therapy, the high midface,
broad interalar distance and prominent high chin appeared to accentuate over time
in relationship to untreated PWS patients. Conversely, broad appearing ears were
not accentuated by growth hormone therapy in the PWS subjects analyzed in this
study.
PMID- 9650765
TI - Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome.
AB - Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18-month
old female with a terminal deletion of the long arm of chromosome 2
[46,XX,del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the
2q37 deletion syndrome, the present observation raises the question of whether a
tumor susceptibility gene maps to chromosome 2q37 and suggests giving
consideration to the possible occurrence of Wilms' tumor in the course of
disease.
PMID- 9650766
TI - A novel mutation of the beta-glucocerebrosidase gene associated with neurologic
manifestations in three sibs.
AB - We report on a sibship in which three members were affected by Gaucher disease.
Molecular analysis of the patients showed homozygosity for a novel mutation
(C5390G) of the beta-glucocerebrosidase gene, resulting in the substitution of
the arginine 353 with a glycine. Western blot analysis showed a reduced amount of
beta-glucocerebrosidase-related polypeptides in fibroblasts. The phenotype
resulting from this mutation is characterized by visceral and skeletal
manifestations. In addition, the presence of seizures and electrophysiological
abnormalities only in the 3 patients and in none of the other unaffected sibs
suggests that the mutation is responsible for neurologic involvement.
PMID- 9650767
TI - Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature.
AB - Low level chromosome mosaicism found at amniocentesis is problematic for
clinicians and patients. We report prenatal diagnosis of a fetus with a rare
karyotype of 47,XX, + 15/46,XX. Second trimester amniocentesis was performed for
advanced maternal age. Fetal ultrasound revealed a hypoplastic right ventricle
and intrauterine growth retardation (IUGR). The rest of the fetal anatomy was
within normal limits. A mosaic karyotype of 47,XX, + 15/46,XX was observed. The
couple interrupted the pregnancy at 19 weeks by dilation and suction evacuation.
Careful evaluation of multiple pieces of fetal parts and placenta revealed one
abnormal finding: a single umbilical artery. Cytogenetic metaphase and
fluorescent in situ hybridization (FISH) interphase analyses of cells from fetal
lung, heart, placenta, and skin revealed the presence of the trisomic line in all
tissues. Molecular analysis demonstrated that the origin of the extra chromosome
15 was maternal, the error most likely occurred in meiosis I and the diploid line
was of biparental inheritance. This case report discusses the associated findings
in this fetus and reviews the literature describing other cases of mosaic trisomy
15.
PMID- 9650768
TI - Molecular and cytogenetic [correction of cytogenate] analysis of an X/autosomal
translocation: 45,X,dic(X;17)(p22.2;p13)
AB - We present an unusual case of monosomy 17p13-pter and monosomy Xp22.2-pter due to
a dicentric translocation chromosome X/17 in a female newborn with severe
anomalies. The karyotype was identified as 45,X,dic(X;17)(p22.2;p13) by high
resolution GTG banding in lymphocytes. R banding showed the translocational X
chromosome to be late replicating, and there was no spreading of X-inactivation
onto the autosomal segment. Furthermore, it could be demonstrated by C banding
that the X-centromere in the translocation chromosome was inactive. The results
of short tandem repeat (STR) typing confirmed the partial monosomy X and 17 as
well as the paternal origin of the two chromosomes X and 17 which were involved
in the translocation chromosome formation. The cell stage of the structural
rearrangement was consistent with paternal meiosis as well as with postzygotic
mitosis. The monosomy was confirmed in lymphocytes and fibroblasts, and mosaicism
was not detected.
PMID- 9650769
TI - Complex chromosomal rearrangements associated with congenital erythrophagocytotic
histiocytosis.
AB - We describe a patient with a congenital malignant blood disorder and a
constitutional de novo chromosomal rearrangement that includes four breakpoints.
By conventional cytogenetic analysis an obviously reciprocal balanced
translocation with the breakpoints 1p36 and 5q11.2 was diagnosed. Due to a
suspicious dark band in the breakpoint area of 1p a more detailed analysis of the
breakpoints was performed using microdissection and reverse chromosome painting.
This revealed a small inversion at 1p36 that must have occurred prior to the
reciprocal translocation. The three breakpoints in chromosome 1 (1p36.11, 1p36.21
and 1p36.31) are within or close by regions known to contain tumor suppressor
genes. The chromosomal rearrangement might have resulted either in a
submicroscopic deletion, in loss of heterozygosity of one or more imprinted
genes, or in gene position effects as possible explanations for the clinical
course of our patient.
PMID- 9650770
TI - Apparent normalisation of fetal renal size in autosomal dominant polycystic
kidney disease (PKD1).
AB - We present a family with adult onset autosomal dominant polycystic kidney disease
(ADPKD) in two generations, linked to the PKD1 locus and with paternal
transmission to the fetus. The fetus carried the PKD1 haplotype and was,
therefore a gene carrier. Progressive hyperechogenic renal enlargement, but no
cysts, was documented by serial fetal ultrasounds at 21, 23 and 34 weeks of
gestation. Surprisingly, the newborn renal scan showed normal sized kidneys with
apparently normal corticomedullary differentiation. However, at 11 months of age,
the evolution of cysts in one kidney, and then in the other kidney at 20 months,
was documented by ultrasound in the absence of clinical symptoms or signs. The
observed normalisation of fetal renal ultrasound appearances at birth has not
previously been described in fetuses presenting with PKD1.
PMID- 9650771
TI - Kabuki (Niikawa-Kuroki) syndrome associated with immunodeficiency.
AB - We report a case of a 19-year-old male with the cardinal features of the Kabuki
syndrome (KS) and, in addition, with severe immunodeficiency. Finding immune
deficiency in a KS patient, prompted us to determine whether this association was
related to a deletion within the DiGeorge chromosomal region. Fluorescence in
situ hybridization (FISH) with the Oncor probe N25(D22S75) revealed no deletion
of 22q11.2 in the patient.
PMID- 9650772
TI - Tetranucleotide repeat polymorphism at the CCSP gene.
PMID- 9650773
TI - A novel Mbo II polymorphism in exon 15 of the human adenomatous polyposis coli
gene.
PMID- 9650774
TI - Cerebral aqueductal stenosis as a presentation of deletion 6q25-qter.
PMID- 9650775
TI - Two cases of prenatally diagnosed diaphragmatic hernia accompanied by the same
undescribed chromosomal deletion (15q24 de novo)
PMID- 9650776
TI - Apolipoprotein E alleles in mothers of trisomy 18 conceptuses.
PMID- 9650777
TI - An alpha-actinin-profilin chimaera with two alternatively operating actin-binding
sites.
AB - Studying the mode of interaction between actin and actin-binding proteins, we
constructed a chimaeric protein consisting of the sequence for bovine profilin I
(P), to which the sequence for the actin-binding domain of Dictyostelium
discoideum alpha-actinin (alphaA1-2) was fused N-terminally. The resulting hybrid
clone was expressed in Escherichia coli, and the chimaeric protein, alphaA1-2P,
purified by affinity chromatography on poly-(L-proline) (PLP) columns and
identified using specific antibodies. High resolution electron microscopy
demonstrated that this protein consists of two discrete subdomains. In
biochemical, viscometric and electron microscopic analyses, we showed that both
modules in this molecule are biologically active. The chimaera binds to poly-(L
proline) and inhibits the polymerization of G-actin in KCl, which is consistent
with the assumption that the profilin part is intact. Inhibition of actin
polymerization in KCl was stronger than that of the parental profilin, and the Kd
value of its interaction with rabbit skeletal muscle actin, as determined by
falling ball viscometry, was smaller (mean value 0.5 x 10(-6) M, as compared to
1.9 x 10(-6) M for bovine profilin). In 2mM MgCl2, the actin polymerized rapidly,
consistent with the interpretation that under these conditions the chimaera, like
profilin, is less efficient as an actin-sequestering agent. In the presence of
alphaA1-2P, the resulting filaments were decorated with particles projecting from
the filament axis. We conclude that under these conditions the alphaA1-2 domain
of alphaA1-2P is preferentially active, attaching the chimaeric particles
laterally to the filaments. Hence, the parental modules combined in alphaA1-2P
permit this molecule to switch from a G-actin- to an F-actin-binding form.
PMID- 9650778
TI - Actin microfilaments are essential for the cytological positioning and morphology
of the Golgi complex.
AB - The organization and function of the Golgi complex was studied in normal rat
kidney cells following disruption of the actin cytoskeleton induced by
cytochalasin D. In cells treated with these reagents, the reticular and
perinuclear Golgi morphology acquired a cluster shape restricted to the
centrosome region. Golgi complex alteration affected all Golgi subcompartments as
revealed by double fluorescence staining with antibodies to the cis/middle
Mannosidase II and the trans-Golgi network TGN38 proteins or vital staining with
the lipid derivate C6-NBD-ceramide. The ultrastructural and stereological
analysis showed that the Golgi cisternae remained attached in a stacked
conformation, but they were swollen and contained electron-dense intra-cisternal
bodies. The Golgi complex cluster remained linked to microtubules since it was
fragmented and dispersed after treatment with nocodazole. Moreover, the
reassembly of Golgi fragments after the disruption of the microtubuli with
nocodazole does not utilize the actin microfilaments. The actin microfilament
requirement for the disassembly and reassembly of the Golgi complex and for the
ER-Golgi vesicular transport were also studied. The results show that actin
microfilaments are not needed for either the retrograde fusion of the Golgi
complex with the endoplasmic reticulum promoted by brefeldin A or the anterograde
reassembly after the removal of the drug, or the ER-Golgi transport of VSV-G
glycoprotein. However, actin microfilaments are directly involved in the
subcellular localization and the morphology of the Golgi complex.
PMID- 9650779
TI - Quantitative immunoelectron microscopy reveals alpha2,6 sialyltransferase is
concentrated in the central cisternae of rat hepatocyte Golgi apparatus.
AB - The Golgi apparatus is a membrane bound organelle involved in synthesis of N
linked oligosaccharides which are trimmed and then lengthened by a series of
sugar transferases adding N-acetylglucosamine, galactose and sialic acid in
sequence. We previously published qualitative work which localized
Galbeta1,4GlcNAc alpha2,6 sialyltransferase of rat hepatocytes to the trans
cisternae and the trans Golgi network. We now report the use of combined
stereological and immunoelectron microscopical techniques for mapping the Golgi
stack composition and distribution of sialyltransferase protein in rat
hepatocytes. The Golgi stack showed substantial variation in composition
consisting of 1, 2, 3, 4, or 5 cisternae with an average of 2.5 cisternae.
Sialyltransferase labeling was mainly located in the central cisternae of the
Golgi stacks irrespective of whether the stacks were oriented in a cis/trans
direction using morphological criteria. Only 20% of the total sialyltransferase
labeling was present in the transmost cisterna and 2% in the trans Golgi Network.
The low labeling in the transmost cisterna was essentially due to the presence of
a sialyltransferase negative cisterna. These data emphasize the importance of
quantitation in obtaining a representative picture of Golgi enzyme distribution
in three dimensions. They indicate that central cisternae, rather than the
transmost cisterna and TGN, function in sialylation along the secretory pathway
of rat hepatocytes.
PMID- 9650780
TI - The leucine-based motif DDQxxLI is recognized both for internalization and
basolateral sorting of invariant chain in MDCK cells.
AB - The major histocompatibility complex (MHC) class II-associated invariant chain
(Ii) contains signals for transport to endocytic compartments where the class II
molecules bind antigenic peptides for presentation to CD4+ T cells. Two leucine
based signals in the Ii cytoplasmic tail can be independently recognized for
endosomal sorting of Ii, and we have recently shown that each signal is
sufficient for basolateral sorting and internalization of Ii in polarized Madine
Darby Canine Kidney (MDCK) II cells. The recognition motif for endosomal sorting
is complex and consists of two critical leucine-like residues as well as
surrounding amino acids. Here, we have analyzed the importance of residues
surrounding the membrane-distal leucine-based signal in basolateral sorting and
internalization of Ii in MDCK II cells. We find that the DDQxxLI motif is
involved in both sorting events indicating the presence of similar signal
recognition components both at the TGN and at the plasma membrane. The identical
motif is required for endosomal localization and internalization of Ii also in
simian COS cells and the human HeLa and M1 cells.
PMID- 9650781
TI - Tyrphostin A9 and wortmannin perturb the Golgi complex and block proliferation of
vascular smooth muscle cells.
AB - To proliferate, vascular smooth muscle cells first convert from a contractile to
a synthetic phenotype. Earlier studies indicate that this process is supported by
fibronectin and accelerated by platelet-derived growth factor (PDGF). Here, the
mechanisms in this transition were further explored. Isolated rat aortic smooth
muscle cells were treated with tyrphostin A9, a PDGF receptor tyrosine kinase
inhibitor, and wortmannin, a phosphoinositide 3-kinase inhibitor. Electron
microscopy did not show any effect on the reorganization of the cells during the
first days in culture, i.e. the loss of actin filaments and the formation of a
large secretory apparatus. Conversely, both drugs caused hypertrophy of the Golgi
complex, with large and partly vacuolized cisternal stacks. Nevertheless, a
juxtanuclear staining pattern for the Golgi enzyme mannosidase II, the coat
protein beta-COP, and the PDGF beta-receptor was retained. Moreover, the serum
induced proliferation of the cells was blocked. These findings suggest that
signaling via PDGF receptor tyrosine kinases and phosphoinositide 3-kinases is
not necessary for the shift of the smooth muscle cells from a contractile to a
synthetic phenotype. On the other hand, these enzymes apparently carry out
important functions in the control of intracellular membrane traffic and cell
division.
PMID- 9650782
TI - Traffic into the prevacuolar/endosomal compartment of Saccharomyces cerevisiae: a
VPS45-dependent intracellular route and a VPS45-independent, endocytic route.
AB - The vps (vacuolar protein sorting) mutants have been used to dissect and
characterize the vacuolar biogenesis pathway in the yeast Saccharomyces
cerevisiae. The vps mutants were isolated through their loss of ability to
correctly sort the vacuolar hydrolase CPY, which travels from Golgi membranes to
the vacuole through a prevacuolar compartment. Over 50 VPS genes have been
divided into 6 classes according to vacuolar morphology. Mutations in any one of
the class E VPS genes, such as VPS27, lead to an exaggerated form of the
prevacuolar compartment. This class E compartment contains endocytosed proteins
as well as proteins en route to the vacuole, and is thus taken to represent an
intersection point between the endocytic and biosynthetic pathways. Mutations in
the class D gene VPS45 can be used to define a second transport intermediate
along the vacuolar biogenesis pathway, Golgi-derived transport vesicles carrying
vacuolar membrane proteins on their way to the vacuole. Here we demonstrate that
the Sec1p-like protein Vps45p is required for the fusion of Golgi-derived
vesicles with the prevacuolar compartment indicating that VPS45 functions before
VPS27 in the vacuolar biogenesis pathway. In addition, we show that VPS45
function is not required for the delivery of endocytosed proteins to the
prevacuolar compartment from the plasma membrane suggesting that the function of
Vps45p is restricted to a single vesicular pathway.
PMID- 9650783
TI - Iodination of mature cathepsin D in thyrocytes as an indicator for its transport
to the cell surface.
AB - Thyrocytes are known for their ability to iodinate thyroglobulin from which the
thyroid hormones are generated. In the intact thyroid gland the iodination
process is almost exclusively executed at the apical plasma membrane of thyroid
epithelial cells. Here, we show that freshly isolated thyrocytes iodinated
polypeptides other than thyroglobulin and that one of the major iodinated
polypeptides was the mature form of the lysosomal protease cathepsin D (CD). The
detection of mature CD as an iodinated polypeptide suggested that a fraction of
the lysosomally maturated enzyme was delivered to the apical plasma membrane
where it became available for iodination. After labeling of thyrocytes with
[35S]methionine/cysteine overnight part of the mature CD was released into the
culture medium. This was abolished by inhibiting maturation of CD with NH4Cl,
indicating that mature CD appeared in the medium after its proteolytic maturation
in an acidic compartment. Besides CD other soluble lysosomal polypeptides like
the beta-N-acetylhexosaminidase and the sphingolipid-activating protein D (Sap D)
were iodinated and partially secreted as mature polypeptides. In contrast, the
membrane-associated lysosomal ceramidase was iodinated and partially secreted as
immature single-chain enzyme and not as fully maturated two-chain enzyme. These
data indicate that a portion of mature CD and other soluble lysosomal enzymes is
delivered from lysosomes to the cell surface whereas some membrane-associated
enzymes from the terminal lysosomal compartment are efficiently excluded from
this process.
PMID- 9650784
TI - Cell fate specification in an in vitro model of neural development.
AB - We have studied in an in vitro model of neural development the effect of
neighboring cells on the fate of single fluorescently labeled precursor cells. In
one line of experiments, PCC7-Mz1 embryonal carcinoma cells were transiently
transfected with "green fluorescent protein" (GFP) and, following incubation with
0.1 microM all-trans retinoic acid (RA), the number and morphology of derivatives
(neuronal or non-neuronal) was determined that form groups of GFP-expressing
cells in a surrounding of unlabeled cells. Because single PCC7-Mz1 cells can
produce single-lineage and mixed-lineage derivatives, they are individually
pluripotent. In another line of experiments, we have analyzed the fate of GFP
expressing PCC7-MzN cells in different cellular environments. Whereas in the
absence of other cells, PCC7-MzN cells exclusively differentiated to neuronal
derivatives following RA induction (Lang, E., M. L. Mazauric-Stuker, A. Maelicke,
J. Cell Biol. 109, 2481-2493 (1989)), they differentiated also to non-neuronal
phenotypes (astrocytes and fibroblasts) when co-cultured with either PCC7-Mz1
stem cells or freshly RA-induced cells. The fate of PCC7-MzN cells could also be
shifted in the absence of other cells when the cells were grown on laminin-coated
surfaces. These results suggest that a putative fate-shifting activity (FSA) is
released by PCC7-Mz1 and PCC7-MzN cells which requires, at least in the case of
MzN cells, presentation by extracellular matrix-like structures in order to
function in cell fate specification. Very few other cell types, in particular
primary cultures of mouse forebrain cells of embryonic day 13, were capable of
shifting the developmental potential of PCC7-MzN cells in a similar manner as
PCC7-Mz1 cells do. We conclude that cell type specification in this model of
neural development may occur by similar mechanisms as have been established in
Drosophila neurogenesis. A default pathway (neuronal) is modulated by lateral
signaling between neighboring cells so that cellular diversity can arise from
initially homogeneous populations of progenitor cells.
PMID- 9650785
TI - Surface exposure of phosphatidylserine during apoptosis of rat thymocytes
precedes nuclear changes.
AB - Cell surface exposure of phosphatidylserine (PS) during apoptosis serves
recognition and removal of the dying cell by phagocytes. Loss of phospholipid
asymmetry and PS exposure is investigated by immunocytochemistry and related to
morphological changes. Loss of membrane asymmetry was determined on dexamethasone
treated rat thymocytes using the PS specific probe annexin V. Thymocytes
incubated in the presence of dexamethasone were studied in time series during the
execution of the apoptotic program. Thymocytes first start to expose PS at their
cell surface. At this initial stage the barrier function of the plasma membrane
remains intact. At a later stage the plasma membrane becomes leaky for compounds
like propidium iodide and subsequently the cell disintegrates into apoptotic
bodies. Microscopical evaluation of dexamethasone-treated thymocytes showed that
the cells with an apoptotic morphology all bound annexin V. The cells with a
normal viable morphology lacked annexin V binding except for those cells that
started to shed small vesicles. These vesicles were positive for annexin V,
indicating a local disturbance of the phospholipid asymmetry. The local exposure
of PS is considered to be a very early event of apoptosis, preceding the full
sequence of morphological changes at the ultrastructural level.
PMID- 9650786
TI - Optical pumping in indium phosphide: 31P NMR measurements and potential for
signal enhancement in biological solid state NMR.
AB - The initial results of optically-pumped, directly-detected NMR experiments on InP
are reported. At low temperatures (4.2 K and above) and in a 9.39 T magnetic
field, irradiation of a sample of an undoped InP wafer with 835-nm-wavelength
light from a diode laser enhances the spin polarization of 31P nuclei near the
sample surface in a manner that depends on the polarization of the light. The
nuclear spin polarization is monitored by direct radio-frequency detection of
nuclear free induction-decay signals. The maximum nuclear spin polarization (Szn>
generated by optical pumping is approximately - 0.004, corresponding to a spin
temperature of -0.5 K. The nuclear spin polarization may be limited in these
experiments by the use of a high photon energy (1.484 eV) relative to the InP
band gap (1.423 eV at low temperatures). It is proposed that optically-pumped InP
may be useful as a source of enhanced nuclear spin polarizations for solid state
NMR measurements on organic and biological overlayers deposited on InP
substrates. Estimates are given for the magnitude of the spin polarization and
the efficiency of the polarization transfer from the semiconductor substrate to
the overlayer that would be required to permit solid state NMR measurements on
sub-nanomole quantities of molecules in the overlayer. These estimates appear
well within the range of possibility.
PMID- 9650787
TI - Microscopic interpretation of optically pumped NMR signals in GaAs.
AB - By numerical modelling and least squares fitting to the field, time and
polarization dependence of optically pumped 69Ga NMR data in semi-insulating GaAs
at low temperature and high field, a microscopic picture of this phenomenon
emerges. Numerical values can be obtained for the key optical pumping parameters:
the correlation time for the electron-nuclear contact interaction, and the
electronic g-factor. The values of these parameters, which are in close agreement
with previously reported values, can be combined with literature estimates for
the average hyperfine interaction and spin diffusion coefficient D to generate
numerical solutions for the Zeeman nuclear spin order, (r,t). The modelling
permits the influence of variations with any other relevant parameter to be
predicted. Experimentally, the optical polarization and time dependence data are
presented. Least squares fits to the optical polarization dependence yield a
value for the optically induced electron spin polarization at the given field,
temperature, and excitation intensity. With the numerical solutions (r,t)
that best fit the available data, the hyperfine frequency shift can be used to
simulate the time evolution of the 69Ga NMR line shape. These simulations provide
guidance on how to optimize the experimental conditions to most effectively
observe hyperfine effects near shallow donors in this particular material.
PMID- 9650788
TI - Solid state NMR studies of photoinduced polarization in photosynthetic reaction
centers: mechanism and simulations.
AB - We simulate Photo-Chemically Induced Dynamic Nuclear Polarization in the 15N
solid-state NMR of 15N-labeled photosynthetic reaction centers using a Radical
Pair Mechanism (RPM). According to the experimental data, the directly polarized
nuclei include all eight nitrogens in the ground state of the bacteriochlorophyll
special pair (P), and N-II in the bacteriopheophytin acceptor (H) [M.G.
Zysmilich, A.E. McDermott, J. Am. Chem. Soc., 116 (1994) 8362-8363.] [M.G.
Zysmilich, A. McDermott, J. Am. Chem. Soc., 118 (1996) 5867-5873.] [M.G.
Zysmilich, A. McDermott, Proc. Natl. Acad. Sci. U.S.A., 93 (1996) 6857-6860.];
other signals are polarized in nonspecifically labeled samples, but the
polarization apparently results from magnetization exchange with neighboring
polarized nitrogens, and these are not treated in this work. Two quantitative
models for the polarization associated with the RPM are presented and are used to
test the validity of the proposal that this mechanism is cooperative in the
reaction centers. The kinetic models can treat the steady state polarizations as
well as the approach to steady state, and in principle could be expanded to
include anisotropic effects, or pulse-probe experiments. Several features of the
detailed simulations of the steady-state amplitudes and the kinetics of the
approach to steady-state are compared with our data, including the signs and
approximate absolute magnitudes of the polarization on the nitrogen nuclei in P
and H(L), and the changes in the relative amplitudes with the change in the
lifetime of the molecular triplet, photoaccumulation time, nuclear relaxation
rate and illumination intensity. The simulations demonstrate that the
polarization intensities are in qualitative agreement with those predicted for
the RPM, including the curious observation of strong polariza-tion on the
pheophytin acceptor for certain experimental conditions. However, this agreement
requires efficient relaxation of the nitrogens on H(L) by 3P, due to a fortuitous
low nanosecond value for the spin-lattice relaxation for the electrons in the
molecular triplet of the donor, T1e of 3P. Whether this fortuitous match is valid
is unproven.
PMID- 9650789
TI - Optical NMR from single quantum dots.
AB - Nuclear magnetic resonance (NMR) from constituent Ga and As nuclei was optically
detected on excitonic recombination in single GaAs quantum dots formed by
interface fluctuations in GaAs/Al0.3Ga0.7As quantum wells. Orientation of the
nuclear spin system by optical pumping causes an Overhauser shift of the
excitonic energy levels proportional to the degree of nuclear orientation. NMR
was subsequently detected by monitoring changes in the combined Overhauser plus
Zeeman splitting of excitons localized in single quantum dots as the RF frequency
was swept through a nuclear resonance. The NMR signals originate from
approximately 10(5) nuclei in the quantum dot-with dimensions of approximately 4
nm X 10 nm X 100 nm--illustrating the extreme sensitivity and spatial resolution
of the technique. NMR from such small structures provides a chemically specific
probe of the local environment on the nanometer scale.
PMID- 9650790
TI - Projection noise in the optically detected magnetic resonance signal of a single
electron spin.
AB - The spin quantum noise owing to a single molecular triplet electron spin jumping
from one eigenstate to another has been detected. As a result of the
superposition of two spin eigenstates in the triplet level of the molecule by a
microwave pi/2-pulse an increase in the noise of the fluorescence intensity of a
single molecule is detected. This increase in noise is attributed to the decay of
coherence between the two spin eigenstates.
PMID- 9650791
TI - Magnetic resonance force microscopy with a ferromagnetic tip mounted on the force
detector.
AB - The Magnetic Resonance Force Microscope (MRFM) presents the opportunity for a
magnetic resonance imaging probe with ultra-high, potentially atomic-scale,
resolution. The successful application of this technique in detection of nuclear
magnetic, electron-spin and ferromagnetic resonance (FMR) highlights its
significant potential. We discuss the capabilities of the MRFM with particular
emphasis on the detection of FMR using MRFM techniques. A crucial remaining
challenge in the development of the magnetic resonance force microscope (MRFM) is
to place the magnetic probe on the mechanical resonator. We address the problem
of spurious detector response arising from interactions between the magnetic tip
and various external applied fields. We show that miniature, magnetically
polarized Nd2Fe14B particles show promise as magnetic probe tips. Our experience
indicates it will be important to minimize the total polarized moment of the
magnetic tip and to ensure that the applied fields are as uniform as possible.
PMID- 9650792
TI - Force-detected magnetic resonance without field gradients.
AB - A novel method of nuclear magnetic resonance (NMR) is described which promises to
be preferable to known general methods at sample length scales below
approximately 100 microm. Its advantages stem from the seemingly paradoxical
combination of a homogeneous static magnetic field and detection of a mechanical
force between a spin-bearing sample and a magnet assembly. In contrast to other
methods of force-detected nuclear magnetic resonance (FDNMR), the method is
characterized by better observation of magnetization, enhanced resolution, and no
gradient (BOOMERANG), and it is generally applicable with respect to sample
composition, pulse sequence, and magnetic field strength. Further advantages of
portability and low cost stem from the small instrument volume and mass and
promise to extend the use of NMR to new applications and environments. A
sensitivity analysis, relevant to spectroscopy or imaging, quantifies the
advantage of BOOMERANG relative to magnetic induction using microcoils and to
FDNMR methods that rely on large gradients of the magnetic field at the sample.
PMID- 9650793
TI - Particle detected Fourier transform NMR at single crystal surfaces--6Li on
Ru(001).
AB - Fourier transform nuclear magnetic resonance at single crystal surfaces is
described. The adsorption of 6Li on Ru(001) is investigated by newly developed
techniques utilizing atomic beam sample preparation and optical detection of the
NMR signal on desorbing atoms (laser induced fluorescence) or ions (beamfoil
spectroscopy). In complete analogy to magnetically detected NMR, the transverse
magnetisation is coherently recorded. This allows pulse NMR to be applied to
surface problems.
PMID- 9650794
TI - Muon spin relaxation studies of interstitial and molecular motion.
AB - The unusual methods of preparation and analysis of spin polarization in muSR
spectroscopy, which exploit the unique properties of the positive muon, are
introduced in this article. Following a summary overview of applications,
particular attention is paid to the problem of spin-lattice relaxation for a muon
experiencing a hyperfine interaction with a single unpaired electron. The
specific cases considered are the interstitial diffusion of muonium--the 1
electron atom which may be considered as a light isotope of hydrogen-and the
molecular dynamics of organic radicals labelled by muonium. Rate equations for
the evolution of population in the hyperfine-coupled spin states are solved
numerically for various relaxation mechanisms. The formalism is equally valid for
conventional ESR studies of paramagnetic states but is pursued specifically to
simulate T1-relaxation in muSR. The simulations are compared with literature
data. Also treated is the case of intermittent hyperfine coupling, appropriate to
electron capture and loss in semiconductors or soliton motion in polymers; for
this, a Monte Carlo approach is used to simulate the muon response. (For low
dimensional motion, the relaxation function is not exponential, so that a unique
value of T1 cannot be defined.) Finally, a proposal is made to implement muon-T1
measurements in the rotating frame; this is designed for the selective study of
electronically diamagnetic muonium states (i.e., those without hyperfine
coupling) in the presence of a paramagnetic muonium or radical fraction.
PMID- 9650795
TI - Nuclear magnetic resonance by measuring reaction yield of spin symmetry species.
AB - It is proposed that the nuclear magnetic resonance of sites which release
dihydrogen can be obtained by measuring the branching fraction to the ortho and
para forms. The motivation is to transform the sensitivity problem from that of
detecting magnetization into the more tractable one of establishing the para and
ortho content of free H2. It is shown with a density operator formalism that the
para mole fraction reports directly on the zero-quantum coherence of the
precursor and that other spin operators may be observed indirectly. Spectra are
simulated for the case of a surface site from which H2 is released.
PMID- 9650796
TI - The excitation of NMR transitions by the current in a sample and the proposals
for its detection.
AB - A new magnetic resonance technique for investigating conducting samples is
described. NMR transitions are excited by the magnetic field of alternating
current which flows across the sample. The dissipation of the energy caused by
NMR transitions results in a change of the impedance of the sample. The NMR
signal is detected as an associated change of the voltage drop across a sample
while passing through the resonance region. It is predicted that the resonance
can be detected by state-of-the-art low-noise superconducting quantum
interference device (SQUID)-based NMR spectrometers. The method is believed to be
useful for investigations of small-volume samples which are inaccessible by other
NMR techniques.
PMID- 9650797
TI - SQUID detected NMR and NQR. Superconducting Quantum Interference Device.
AB - The dc Superconducting QUantum Interference Device (SQUID) is a sensitive
detector of magnetic flux, with a typical flux noise of the order 1 muphi0 Hz(
1/2) at liquid helium temperatures. Here phi0 = h/2e is the flux quantum. In our
NMR or NQR spectrometer, a niobium wire coil wrapped around the sample is coupled
to a thin film superconducting coil deposited on the SQUID to form a flux
transformer. With this untuned input circuit the SQUID measures the flux, rather
than the rate of change of flux, and thus retains its high sensitivity down to
arbitrarily low frequencies. This feature is exploited in a cw spectrometer that
monitors the change in the static magnetization of a sample induced by radio
frequency irradiation. Examples of this technique are the detection of NQR in
27Al in sapphire and 11B in boron nitride, and a level crossing technique to
enhance the signal of 14N in peptides. Research is now focused on a SQUID-based
spectrometer for pulsed NQR and NMR, which has a bandwidth of 0-5 MHz. This
spectrometer is used with spin-echo techniques to measure the NQR longitudinal
and transverse relaxation times of 14N in NH4ClO4, 63+/-6 ms and 22+/-2 ms,
respectively. With the aid of two-frequency pulses to excite the 359 kHz and 714
kHz resonances in ruby simultaneously, it is possible to obtain a two-dimensional
NQR spectrum. As a third example, the pulsed spectrometer is used to study NMR
spectrum of 129Xe after polariza-tion with optically pumped Rb. The NMR line can
be detected at frequencies as low as 200 Hz. At fields below about 2 mT the
longitudinal relaxation time saturates at about 2000 s. Two recent experiments in
other laboratories have extended these pulsed NMR techniques to higher
temperatures and smaller samples. In the first, images were obtained of mineral
oil floating on water at room temperature. In the second, a SQUID configured as a
thin film gradiometer was used to detect NMR in a 50 microm particle of 195Pt at
6 mT and 4.2 K.
PMID- 9650798
TI - Ion-transporting ATPases as ion channels.
AB - Ion-transporting ATPases (pumps) hydrolyze ATP to maintain ion gradients across
cell membranes. A presupposition for the maintenance of the gradients is that the
ionophore of the pump that conducts the ions is accessible only from one of the
two surfaces of the plasma membrane at any given time. Thus, a characteristic
feature of pumps is an occluded state of the transported ions, whereas ion
channels upon stimulation remain open at both ends and allow ions to flow through
them down their chemical gradients. Recent experiments, however, provide evidence
that a channel, simultaneously open on both sides of the plasma membrane, can
also be formed within the mammalian sodium pump (Na+,K+-ATPase) upon its
interaction with the marine toxin palytoxin, thus underlining common structural
features shared by channels and pumps. This assumption is further supported by
the demonstration of structural and functional homology between the extracellular
loop of the sodium pump alpha subunit connecting the M7 and M8 transmembrane
spans and the P-loops of Na+ channels. Possibly, pumps are simply channels that
are able to be gated by ATP and its product phosphate.
PMID- 9650799
TI - [125I]Tyr10-cortistatin14 labels all five somatostatin receptors.
AB - The recently cloned rat preprocortistatin, which shows homology to the
preprosomatostatin peptide, is thought to be enzymatically cleaved to
cortistatin14 (CST14) similarly to somatostatin14 (SRIF14). High structural
similarity of cortistatin14 compared to SRIF14 suggested binding properties to
somatostatin receptors similar to SRIF14. In the present study, we expressed
stably the five human somatostatin receptor subtypes (hsst1-hsst5) in CCL39 cells
(Chinese hamster lung fibroblast cells). The receptors were labelled with an
iodinated analogue of CST14 ([125I]Tyr10)-cortistatin14, [125I]Tyr10-CST) to
establish the pharmacological profile of hsst1-hsst5 sites labelled with
[125I]Tyr10-CST. In parallel, [Leu8,D-Trp22,125I-Tyr25]-SRIF28 ([125I]LTT-SRIF28)
was used as a control at the five recombinant SRIF receptors stably expressed in
CCL39 cells. High affinity [125I]Tyr10-CST binding could be demonstrated to all
five recombinant somatostatin receptor subtypes. The pKd (-log mol/l) and Bmax
values (fmol/mg) for hsst1-5 receptors were: 10.02+/-0.04, 220+/-30; 9.45+/-0.09,
340+/-70; 10.06+/-0.11, 340+/-50; 9.67+/-0.14, 340+/-110 and 10.33+/-0.03, 5630+/
1330, respectively. The pharmacological profiles determined with [125I]Tyr10-CST
and [125I]LTT-SRIF28 were very similar at every receptor studied. These data
suggest that cortistatin and somatostatin have similar high affinity for SRIF
receptors. None of the receptors showed marked selectivity for either CST14/CST17
or the somatostatins. In conclusion, the data show that cortistatin and
somatostatin have very similar high affinity to all five recombinant somatostatin
receptors. It remains to be seen whether there are specific receptors which bind
only somatostatins or cortistatins.
PMID- 9650800
TI - Interaction of 5-HT1B/D ligands with recombinant h 5-HT1A receptors: intrinsic
activity and modulation by G-protein activation state.
AB - Many 5-HT1B/D receptor ligands have affinity for 5-HT1A receptors. In the present
study, the intrinsic activity of a series of 5-HT1B/D ligands was investigated at
human 5-HT1A (h 5-HT1A) receptors by measuring G-protein activation in
recombinant C6-glial and HeLa membranes, using agonist-stimulated [35S]GTPgammaS
binding. In these two membrane preparations, the density of h 5-HT1A receptors
(i.e., 246 to 320 fmol mg(-1) protein) and of their G-proteins, and the receptor:
G-protein density ratio (0.08 to 0.18) appeared to be similar. It was found that:
(i) the maximal [35S]GTPgammaS binding responses induced by the 5-HT1B/D receptor
ligands in the HeLa preparation at 30 microM GDP were comparable to that of the
native agonist 5-HT; (ii) as compared to 5-HT (1.00), similar potencies but lower
maximal responses were observed in the C6-glial preparation at 0.3 microM GDP for
zolmitriptan (0.89), dihydroergotamine (0.81), rizatriptan (0.71), CP122638
(0.69), naratriptan (0.60) and sumatriptan (0.53); and that (iii) maximal
[35S]GTPgammaS binding responses induced by 5-HT1B/D ligands in the C6-glial
preparation were either unaffected or significantly enhanced by increasing the
GDP concentration from 0.3 to 30 microM and higher concentrations. These features
differ from those observed with 5-HT1A receptor agonists; the latter display the
same rank order of potency and efficacy in both membrane preparations, and
increasing the amount of GDP with C6-glial membranes results in an attenuation of
both the agonist's maximal effect and the apparent potency of partial agonists.
The differential regulation of 5-HT1A and 5-HT1B/D agonist responses by GDP
suggests that different G-protein subtypes are involved upon 5-HT1A receptor
activation by 5-HT1A and 5-HT1B/D agonists.
PMID- 9650801
TI - In vivo labelling of the mouse brain 5-hydroxytryptamine1A receptor with the
novel selective antagonist 3H-NAD-299.
AB - The in vivo labelling of 5-hydroxytryptamine (5-HT)1A receptors in the mouse
brain was studied with the novel selective 5-HT1A receptor antagonist, NAD-299
((R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide
hydrogen (2R,3R)-tartrate monohydrate). 3H-NAD-299 was injected in a tail vein
and the radioactivity in various brain regions was determined. More than 90% of
the radioactivity in hippocampus, 15 min after the injection, was intact NAD-299.
At this time the amount of 3H-NAD-299 was highest in hippocampus followed by
frontal cortex, mesencephalon, hypothalamus, striatum and cerebellum. The
specific accumulation of radioactivity (after subtracting cerebellum values) in
frontal cortex and hippocampus was maximal 10 to 30 min after the injection and
had almost disappeared after 2 h. Saturation kinetics derived Bmax (pmol/g wet
weight tissue) values of 19.6+/-2.0 in frontal cortex and 38.0+/-3.5 in
hippocampus. The apparent Kd values expressed in nmol/kg 3H-NAD-299 injected,
were 12.3+/-2.2 in frontal cortex and 20.3+/-3.1 in hippocampus. The 5-HT1A
receptor antagonist, WAY-100,635 competitively inhibited the specific
accumulation of 3H-NAD-299 and was about equipotent with unlabelled NAD-299 with
ED50 values of 20-30 nmol/kg s.c. These compounds were about 10 times more potent
than the 5-HT1A receptor antagonists, p-MPPI and NDL-249 and 100 times more
potent than (S)-UH-301. 5-HT1A receptor agonists, e.g. 8-OH-DPAT and flesinoxan
and partial agonists, e.g. pindolol, buspirone and ipsapirone had low potency in
this in vivo assay. Spiperone and methiothepin inhibited the 3H-NAD-299
accumulation at 10 micromol/kg s.c. The alpha1-adrenoceptor antagonist, prazosin
at 2 micromol/kg s.c. increased significantly the specific accumulation of 3H-NAD
299. Pretreatment of the mice with the non-selective, irreversible receptor
antagonist, EEDQ produced a dose related long-lasting decrease in the
accumulation of 3H-NAD-299. It is concluded that NAD-299 is a very suitable
ligand for studies of 5-HT1A receptors in the brain in vivo.
PMID- 9650802
TI - Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and
memory in the elevated plus-maze test in mice.
AB - Effects of FUB 181 [3-(4-chlorophenyl)propyl-3-(1H-imidazol-4-yl)propyl ether], a
novel histamine H3-receptor antagonist, on a scopolamine-induced learning deficit
in the elevated plus-maze test were studied in mice. FUB 181 alone (2.5 and 5
mg/kg, i.p.) ameliorated the scopolamine-induced learning deficit in mice. This
effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-alpha
methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg,
i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain
barrier. However, the ameliorating effect of FUB 181 (2.5 mg/kg) was not
antagonized by either terfenadine (10 mg/kg, i.p.), a histamine H1-receptor
antagonist with poor penetration of the blood-brain barrier, or zolantidine (20
mg/kg, i.p.), a centrally effective histamine H2-receptor antagonist. In a
biochemical study, FUB 181 had no significant effect on either acetylcholine or
choline level in mice brain at the doses tested. These findings suggest that FUB
181 increases the release of histamine by blocking presynaptic histamine H3
autoreceptors, and that released histamine in turn activates postsynaptic H1 and
H2 receptors, predominantly histamine H1 receptors, and in this fashion improves
learning and memory in mice. Our findings also suggest that the histaminergic
system may play an important role in learning and memory, and that FUB 181 may be
a clinical candidate for the therapy of dementia.
PMID- 9650803
TI - Role of vasopressin on excitatory amino acids mediated pressor responses in the
periaqueductal gray area.
AB - In order to evaluate the role played by vasopressin on pressor responses elicited
by stimulation of the periaqueductal gray (PAG) area by excitatory amino acids we
carried out in vivo studies in genetically vasopressin deficient rats
(Brattleboro). Microinjections of 1-glutamic acid (glutamate, 0.6 to 60 nmol/rat)
or N-methyl-d-aspartic acid (NMDA, 0.07 to 7 nmol/rat) into the PAG area of
freely moving Brattleboro rats induced increases of arterial blood pressure
values significantly lower than those obtained in Long Evans rats (control)
(glutamate in Brattleboro rats: from +2+/-1 mmHg to 16+/-3 mmHg; glutamate in
Long Evans rats: from +16+/-2 mmHg to +36+/-4 mmHg; NMDA in Brattleboro rats:
from +5+/-2 mmHg to +34 +/-8 mmHg; NMDA in Long Evans rats: from +18+/-7 mmHg to
80+/-9 mmHg; n=5). Similarly, in anaesthetized Brattleboro rats (urethane 1.2
g/kg i.p.) pressor responses to NMDA microinjections (0.7 nmol/rat) into the PAG
area were significantly lower than in Long Evans rats (controls) (+15+/-3 mmHg vs
+24+/-4 mmHg). In Long Evans rats NMDA injection also reversed blood pressure
decrease induced by ganglionic blocker, hexamethonium and/or losartan (3 mg/kg
i.v.), an AT1 receptor antagonist. In Brattleboro rats, NMDA injection did not
reverse blood pressure decreases induced by hexamethonium (5 mg/kg i.v.).
Moreover, hexamethonium induced blood pressure decrease was not reversed by
acetylcholine injection (137 nmol/rat) into the PAG area of anaesthetized Long
Evans rats, but if injected before hexamethonium, acetylcholine was able to
increase blood pressure (+25+/-3 mmHg). Our results document: i) the importance
of the PAG area in the control of cardiovascular system; ii) the involvement of
excitatory amino acids in the neural control of vasopressin release; iii) the
close relationship between glutamate and vasopressin in the central blood
pressure regulation.
PMID- 9650804
TI - Effects of P2-receptor agonists on sympathetic neuroeffector transmission in the
rat isolated anococcygeus muscle.
AB - The effects of nicotinamide adenine dinucleotide phosphate (NADPH), alpha,beta
methylene adenosine 5'-triphosphate (alpha,beta-MeATP), L-beta,gamma-methylene
adenosine 5'-triphosphate (L-beta,gamma-MeATP), 2-methylthio-adenosine 5'
triphosphate (MeSATP) and adenosine-5-O-(2'-thiodiphosphate) (ADPbetaS) were
investigated on the contractions to electrical field stimulation in the rat
anococcygeus muscle. Stimulation-induced contractions were not affected by L
beta,gamma-MeATP (3-100 microM) or MeSATP (3-100 microM), but were enhanced by
NADPH (10-100 microM), alpha,beta-MeATP (3-30 microM) and ADPbetaS (3-10 microM)
in a concentration-dependent manner, and the enhancements were antagonised by the
P2-receptor antagonist suramin (100 microM). The enhancement produced by
alpha,beta-MeATP (10 microM) and ADPbetaS (10 microM) was also antagonised by
pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (10 microM) and reactive
blue 2 (100 microM). The enhancement produced by alpha,beta-MeATP (10 microM) was
not altered by NG-nitro-L-arginine methyl ester (100 microM), desipramine (1
microM) or idazoxan (0.1 microM) excluding, respectively, the possible
involvement of nitric oxide, neuronal amine uptake or alpha2-autoinhibition of
noradrenergic transmission. Contractions elicited by low (0.1 and 0.3 microM) but
not by higher (1 and 3 microM) concentrations of exogenously applied
noradrenaline were enhanced by alpha,beta-MeATP (10 microM). Neither the resting
nor the stimulation-induced effluxes of radioactivity from [3H]-noradrenaline
labelled anococcygeus muscles were affected by alpha,beta-MeATP (10-100 microM).
The findings suggest that P2-receptors subserve the enhancing actions of NADPH,
alpha,beta-MeATP and ADPbetaS on sympathetic neuroeffector transmission; however,
the subtype of P2-receptor involved and its location remain unclear.
PMID- 9650805
TI - Selective inhibition by riluzole of voltage-dependent sodium channels and
catecholamine secretion in adrenal chromaffin cells.
AB - We examined the effects of riluzole, a neuroprotective drug, on voltage-dependent
Na channels, nicotinic receptors, and voltage-dependent Ca channels, as well as
catecholamine secretion, in comparison with those of verapamil and nicardipine,
in primary cultures of bovine adrenal chromaffin cells. Riluzole inhibited
veratridine-induced 22Na influx via voltage-dependent Na channels even in the
presence of ouabain, an inhibitor of Na,K-ATPase. Blockade of Na channels by
riluzole was concentration-dependent with an IC50 of 5.3 microM. It was
associated with a similar concentration-related reduction of veratridine-induced
45Ca influx via voltage-dependent Ca channels, and of catecholamine secretion.
Riluzole had no effect on 45Ca influx caused by high K, which directly activates
voltage-dependent Ca channels, and on nicotine-induced 22Na influx, which passes
through the nicotinic receptors. Verapamil and nicardipine attenuated 22Na influx
caused by veratridine or nicotine at the same concentrations as they suppressed
high K-induced 45Ca influx. The inhibitory effect of riluzole on veratridine
induced 22Na influx disappeared at high concentrations of veratridine. A
potentiation of veratridine (site 2 toxin)-induced 22Na influx caused by alpha
scorpion venom (site 3 toxin), beta-scorpion venom (site 4 toxin), or brevetoxin
PbTx-3 (site 5 toxin), occurred in the presence of riluzole in the same manner as
in control cells. These results suggest that riluzole binds to the veratridine
site in voltage-dependent Na channels. It does not impair the cooperative
interaction between the functional peptide segments of Na channels, but
selectively inhibits gating of Na channels, thereby reducing Ca influx via Ca
channels and catecholamine secretion. In contrast, verapamil and nicardipine
suppress Na influx both Na channels and nicotinic receptors.
PMID- 9650806
TI - Effect of the Na+-channel modulator BDF 9148 on Ca2+-sensitivity and force of
contraction of hypertrophic myocardium from transgene rats harboring the mouse
Renin gene (TG(mREN2)27).
AB - The present study aimed to investigate the inotropic effect of the Na+-channel
modulator BDF 9148 in hypertrophic myocardium compared to control tissue. Thus,
TG(mREN2)27 rats (TGR), a model with hypertension induced cardiac hypertrophy,
was compared with age matched Sprague-Dawley rats (SPDR). The effect of BDF 9148
(0.01-10 microM) on force of contraction (1 Hz, 37 degrees C), the force
frequency relationship (0.5-7 Hz) and the frequency-dependent diastolic tension
(0.5-7 Hz) was studied on left ventricular papillary muscles from SPDR and TGR.
Chemically skinned muscle fibers of the same hearts were used to examine the
influence of BDF 9148 on the Ca2+-sensitivity of the contractile proteins. For
control the Ca2+-sensitizer EMD 57033 was examined. In addition the Na+/K+-ATPase
activity was measured in both, SPDR and TGR. BDF 9148 showed a concentration
dependent positive inotropic effect in SPDR and TGR cardiac preparations.
Comparing SPDR and TGR, a higher effectiveness of BDF 9148 on TGR was found,
while the potency was unchanged. With increasing stimulation rates a significant
higher decrease in force of contraction in TGR compared to SPDR was observed. In
addition, a significant higher increase in diastolic tension was found in TGR.
After exposure to 1 microM BDF 9148 the decrease in force of contraction was
significantly reduced in both SPDR and TGR, while only in TGR the increase in
diastolic tension was reduced. BDF 9148 had no effect on the Ca2+-sensitivity or
maximal developed tension of skinned fiber preparations from SPDR or TGR. In
contrast, the Ca2+-sensitizer EMD 57033 increased the Ca2+-sensitivity. The
activity of the Na+/K+-ATPase was significantly reduced in TGR compared to
controls. CONCLUSIONS: The Na+-channel modulator BDF 9148 was more effective in
hypertrophic compared to control myocardium in increasing force of contraction,
enhancing frequency-dependent force generation and reducing diastolic tension.
These effects were not mediated via interaction with the contractile apparatus.
The enhanced effectiveness of Na+-channel modulation in hypertrophic myocardium
could result from alterations of the Na+ homeostasis, i. e. a reduced Na+/K+
ATPase activity.
PMID- 9650807
TI - Inhibition of the delayed rectifier K current in guinea-pig cardiomyocytes by
thiamine tetrahydrofurfuryl disulfide.
AB - We examined effect of thiamine tetrahydrofurfuryl disulfide on
electrophysiological characteristics of single atrial myocytes, obtained by
digestion of guinea-pig heart, using collagenase. Membrane potential and ion
channel current in the atrial myocytes were recorded by the patch clamp method.
Thiamine tetrahydrofurfuryl disulfide prolonged action potentials at cycle
lengths from 250 to 10,000 ms. The degree of thiamine tetrahydrofurfuryl
disulfide-induced prolongation was similar among these cycle lengths. Thiamine
tetrahydrofurfuryl disulfide inhibited the delayed rectifier K+ current, without
affecting Ca2+ current and inward-rectifier K+ current. Thiamine
tetrahydrofurfuryl disulfide blocked the delayed rectifier K+ current in voltage-
and time-independent manner, indicating that thiamine tetrahydrofurfuryl
disulfide blocked both subtypes of the delayed rectifier K+ current (rapid and
slow components). Thiamine, the parent molecule of thiamine tetrahydrofurfuryl
disulfide, blocked the delayed rectifier K+ current only when thiamine was
applied intracellularly. Thiamine tetrahydrofurfuryl disulfide may be converted
to thiamine in the cytoplasm, and then may block the the delayed rectifier K+
channel from the intracellular side. Although thiamine tetrahydrofurfuryl
disulfide (or thiamine) has some of the properties of class III antiarrhythmics
agents, thiamine tetrahydrofurfuryl disulfide did not exhibit reverse use
dependent prolongation of action potential.
PMID- 9650808
TI - Autoreceptors can modulate 5-hydroxytryptamine release from porcine and human
small intestine in vitro.
AB - The effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists were
studied on the release of 5-HT from enterochromaffin cells of incubated strips of
porcine and human small intestine. Tetrodotoxin (1 micromol/l) was present in the
incubation medium to block neuronally mediated inputs to the enterochromaffin
cells. The 5-HT1A receptor agonist (+)-8-hydroxy-dipropylaminotetralin (8-OH
DPAT, 1 micromol/l) and the 5-HT2 receptor agonist alpha-methyl-5-HT (1
micromol/l) increased 5-HT release by 40% in about 60% of the human preparations.
These agonists showed no effect on 5-HT release in porcine intestinal mucosa. The
5-HT3 receptor agonist 2-methyl-5-HT (3-100 micromol/l) increased 5-HT release in
both species by 60% (pig) and 90% (man), respectively. These stimulatory effects
were antagonized by tropisetron (10 nmol/l). The 5-HT4 receptor agonist 5
methoxytryptamine (0.3-30 micromol/l) reduced 5-HT release by about 50% in both
species. These inhibitory effects were antagonized by tropisetron (3 micromol/l).
The basal outflow of 5-HT from the intestinal mucosa was not significantly
affected by tropisetron (10 nmol/l; 3 micromol/l). The specific 5-HT4 receptor
antagonist GR 113808 ((1-[2-methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-1
methyl-1H-ind ole-3-carboxylate) (0.1 micromol/l) which by itself did not
significantly affect 5-HT release from human duodenal specimens blocked the
inhibitory effect of 5-methoxytryptamine (30 micromol/l). These findings indicate
that stimulatory 5-HT3 and inhibitory 5-HT4 receptors are present on
enterochromaffin cells of the porcine and human intestinal mucosa. Under the
present experimental conditions endogenous 5-HT does not significantly activate
these receptors. Stimulatory 5-HT1A and 5-HT2 receptors may additionally be
present on human enterochromaffin cells.
PMID- 9650809
TI - Phorbol ester-induced contractions of mouse detrusor muscle are inhibited by
nifedipine.
AB - The effects of phorbol esters on contractions of detrusor strips isolated from
mouse urinary bladder were studied. Beta-phorbol-12,13-dibutyrate (beta-PDBu, 10
nM) significantly enhances both the neurogenic and myogenic detrusor contractions
to a similar extent. By contrast, an inactive isoform of protein kinase C (PKC)
stimulation, alpha-phorbol-12,13-dibutyrate (100 nM) has no such enhancing effect
on the muscle contraction. The effect of beta-PDBu was dependent on the
extracellular Ca2+ concentration. Nifedipine (0.3 microM, a L-type Ca2+ channel
blocker), staurosporine (1 microM) and bisindolylmaleimide I (microM, a selective
PKC inhibitor) but not omega-conotoxin GVIA (an N-type Ca2+ channel blocker)
abolished the enhancing effect of beta-PDBu. In other words, beta-PDBu failed to
augment the nifedipine-insensitive component of the muscle contraction. Moreover,
beta-PDBu not only enhances the muscle response induced by exogenous agonists
(acetylcholine or ATP) and KCl but also increases the resting tone of detrusor
muscle, an effect which is also inhibited by nifedipine and bisindolylmaleimide
I. From these findings, it is concluded that the enhancing effect of beta-PDBu is
due to activation of the L-type Ca2+ channel through phosphorylation by protein
kinase C. This allows more Ca2+ influx from the extracellular medium, leading to
an increase in the contractions of the mouse detrusor muscle.
PMID- 9650810
TI - Protective effect of the combined treatment of pancreatic and neutrophil elastase
inhibitors on acute pancreatitis elicited by lipopolysaccharide in rats given
intraductal injection of taurocholate plus trypsin.
AB - A severe acute pancreatitis was produced by intraperitoneal injection of
lipopolysaccharide (LPS) in rats with preexisting hemorrhagic and necrotizing
pancreatitis induced by retrograde injection of a 5% taurocholate plus 1% trypsin
solution into the pancreatic duct. Mortality and time-course changes in
pancreatic, hepatic, renal and pulmonary functions, and organ myeloperoxidase
(MPO) levels were examined in this model. LPS at an intraperitoneal dose of 30
mg/kg, which scarcely caused death and had no marked effect on serum parameters
and organ MPO levels in rats without pancreatitis, increased the mortality in
rats with taurocholate plus trypsin-induced pancreatitis. Pancreatic weight and
ascitic volume increased in rats with taurocholate plus trypsin-induced
pancreatitis regardless of the presence or absence of LPS. Serum amylase and
lipase levels were also significantly increased in rats with induced
pancreatitis, but was higher in the group given LPS. Serum glutamic oxaloacetic
transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen
(BUN) and creatinine levels were significantly elevated in LPS-treated rats with
induced pancreatitis, whereas levels in rats with induced pancreatitis not given
LPS were only slightly elevated. Renal weight was also significantly increased in
rats with induced pancreatitis despite the presence or absence of LPS. In LPS
treated rats with induced pancreatitis, the arterial oxygen pressure, pulmonary
weight and pulmonary MPO level were significantly elevated. However, the MPO
level in the kidney in these rats was not different from that in control rats,
indicating that the renal dysfunction was not produced by the infiltration of
neutrophils into the kidney. Increase in the pancreatic MPO level was observed in
rats with induced pancreatitis, but combination treatment with LPS did not raise
it. Protective effects of prophylactic treatment of 2-(3-methylsulfonylamino-2
oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2
oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, and
trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 2), a pancreatic
elastase inhibitor, on mortality were also examined in this model. Results were
compared with that of the combined treatment of compound 1 and compound 2. In LPS
treated rats with taurocholate plus trypsin-induced pancreatitis, the combined
treatment of compound 1 (2 mg/kg/h) and compound 2 (30 mg/kg/h) significantly
reduced mortality, whereas single treatment of compound 1 or compound 2 did not
show the beneficial effect. These results suggest that marked hepatic and renal
dysfunction accompanies pancreatitis in this pancreatitis model rats, which may
be good models for acute pancreatitis in humans. It is also suggested that
neutrophil and pancreatic elastases may be synergistically involved in the
pathogenesis of acute pancreatitis in this model.
PMID- 9650811
TI - Suppression of leukotriene B4 and tumour necrosis factor alpha release in acute
inflammatory responses by novel prenylated hydroquinone derivatives.
AB - A series of prenyl hydroquinone derivatives synthesized as structural analogs of
marine products were tested for their effects on inflammatory responses in vitro
and in vivo. 2-Prenyl-1,4-hydroquinone (H1), 2-diprenyl-1,4-hydroquinone (H2), 2
triprenyl-1,4-hydroquinone (H3) and 2-tetraprenyl-1,4-hydroquinone (H4) scavenged
reactive oxygen species and inhibited 5-lipoxygenase (5-LO) activity in human
neutrophils. The inhibition of 5-LO activity was demonstrated in vivo in the
mouse air pouch injected with zymosan and arachidonic acid-induced ear
inflammation. The four compounds suppressed the production of tumour necrosis
factor alpha (TNFalpha) in J774 cells stimulated with lipopolysaccharide (LPS)
and also in vivo in the mouse air pouch injected with zymosan. In addition, all
prenyl-hydroquinones inhibited the release of nitrite and PGE2 in LPS-stimulated
J774 cells, without direct effects on cyclo-oxygenase-1 (COX-1), cyclo-oxygenase
2 (COX-2) or inducible nitric oxide synthase (iNOS) activities in several cell
free systems. The reduction in the length of the lateral chain in prenyl
hydroquinones (1-4 isoprene units) with respect to their marine analogs (7-8
isoprene units) has improved the anti-inflammatory activity of this class of
compounds. Marine natural products may be a model to design new anti-inflammatory
agents.
PMID- 9650812
TI - Inhibition of interleukin-4 and interleukin-13 release from immunologically
activated human basophils due to the actions of anti-allergic drugs.
AB - Human basophils have recently been shown to rapidly produce and release
interleukin (IL-)4 and IL-13 as well as histamine and eicosanoids. Since both IL
4 and IL-13 can initiate and maintain late phase allergic reactions we addressed
whether some widely used anti-allergic drugs can inhibit the anti-IgE induced
release of these cytokines from enriched human basophils. Basophils were enriched
(47-92% purity) by Ficoll density centrifugation followed by elutriation and
negative selection of contaminating cells using immunomagnetic beads. Basophils
were stimulated with sub-optimal dilutions of anti-IgE in the presence or absence
of various drugs and the release of histamine and cytokines were measured after
30 min and 4 h, respectively. The beta-2 agonist salmeterol, the H1-receptor
antagonist terfenadine and the phosphodiesterase inhibitor theophylline inhibited
the release of IL-4 and IL-13 by more than 50% following 4 h of basophil
stimulation with anti-IgE. These drugs also inhibited the release of histamine
following 30 min stimulation, although with less efficacy than for IL-4 and IL
13. Short preincubation of basophils with salmeterol or terfenadine before
stimulation gave rise to significantly greater inhibition of histamine release
but had less effect on the inhibition of cytokine release. The effects of
theophylline, however, were not significantly affected by preincubation of the
cells with the drug. In contrast to the aforementioned drugs, salbutamol and
cetirizine were ineffective at inhibiting both histamine and cytokine release
from basophils. These results suggest that a number of anti-allergic drugs may
mediate their effects, in part, in reducing late phase allergic responses due to
their actions on IL-4 and IL-13 secretion from basophils.
PMID- 9650813
TI - Nitric oxide inhibits isoprenaline-induced positive inotropic effects in normal,
but not in hypertrophied rat heart.
AB - Evidence has accumulated that, in the rat heart, nitric oxide (NO) inhibits beta
adrenoceptor-mediated positive inotropic effects. The aim of this study was to
investigate whether this effect of NO may be altered in cardiac hypertrophy. For
this purpose we studied the effects of the NO-donor SNAP (S-nitroso-N-acetyl-D,L
penicillamine) on isoprenaline-induced positive inotropic effects in left
ventricular strips from three models of cardiac hypertrophy: a) 12-16 weeks old
male spontaneously hypertensive rats (SHR) vs. age-matched normotensive Wistar
Kyoto (WKY) rats, b) six weeks old male Wistar WKY-rats sub-totally
nephrectomized (SNX) 7 weeks after SNX vs. sham-operated rats (SOP) and c) four
weeks old male Wistar WKY-rats supra-renal aortic-banded (AOB, band diameter 1.0
mm) 8 weeks after AOB vs. SOP. In all three models of cardiac hypertrophy the
heart weight/body weight ratio was significantly higher than in their respective
controls. On isolated electrically driven ventricular strips isoprenaline (10(
10)-10(-5) M) caused concentration-dependent increases in force of contraction.
Maximal increases (Emax) were similar in SHR vs. WKY-rats, but reduced in SNX-
(2.9+/-0.29 vs. 5.1+/-0.34 mN, p<0.01) and AOB-rats (2.3+/-0.37 vs. 4.2+/-0.33
mN, p<0.01). In control rats (WKY and the respective SOP) the NO-donor SNAP (10(
5) M) caused a significant rightward-shift of the concentration-response curve
for isoprenalinel; this rightward-shift could be inhibited by methylene blue (10(
5) M). In ventricular strips of SHR, SNX- and AOB-rats, however, 10(-5) M SNAP
failed to significantly affect isoprenaline-induced positive inotropic effect. We
conclude that in cardiac hypertrophy effects of NO are attenuated. Such an
impairement of the NO-system could contribute to the development and/or
maintenance of cardiac hypertrophy.
PMID- 9650814
TI - The role of carbon monoxide in the regulation of neuroendocrine function.
AB - This paper discusses the current evidence supporting the notion that endogenous
carbon monoxide (CO) is a modulator of neuroendocrine function. CO is normally
formed in the body during the enzymatic catabolism of heme moieties by heme
oxygenase (HO). Three HO isoforms have been described to date: HO-1, HO-2 and HO
3. In the brain, CO is principally generated by HO-2 but, in discrete brain areas
such as the paraventricular nuclei of the hypothalamus, a role for HO-1 is also
possible. Moreover, under pathological conditions, the latter isoform is
expressed by activated glial cells. The possible contribution by the recently
described HO-3 remains to be established. Once formed, CO exerts its biological
effects mainly via the activation of soluble guanylyl cyclase, but alternative
signaling mechanisms, such as the activation of cyclooxygenase or the inhibition
of cytochrome P450, have also been reported. In in vitro studies, the formation
of CO within the hypothalamus has been associated with inhibition of the release
of hormones such as corticotropin-releasing hormone, arginine vasopressin and
oxytocin involved in hypothalamo-pituitary-adrenal axis activation and,
conversely, with stimulation of luteinising hormone-releasing hormone release,
thus suggesting that the gas may have a neuroendocrine role which may be to
prevent over-exuberant activation of the hypothalamo-pituitary-adrenal axis and
inhibition of reproductive processes within the hypothalamus during stress. At
present, however, the possible pathophysiological relevance of the in vitro
observations remains to be demonstrated.
PMID- 9650815
TI - Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha
on the core body temperature of mice.
AB - Lipopolysaccharide (LPS) and homologous cytokines were tested for their effect on
core temperature in mice using battery-operated telemetric devices placed in the
peritoneal cavity. One microgram LPS injected intraperitoneally (i.p.) induced a
biphasic effect on core body temperature (Tc), a rapid decrease in Tc with a peak
around 30-45 min followed by a prolonged rise around 150-300 min. When a higher
dose of LPS (5 microg) was used, the hypothermia was increased in magnitude and
lasted much longer, and no fever was observed. Both the decrease and the increase
in Tc caused by LPS were prevented by pretreating the mice with indomethacin, a
cyclooxygenase inhibitor, but not by a nitric oxide synthase inhibitor. Mouse
interleukin-1beta (mIL-1beta, 100 ng, i.p.) induced changes resembling those to
LPS, a short-lived decrease in Tc, followed by a small increase. When 1 microg
mIL-1beta was injected a profound hypothermia lasting more than 3 h was observed.
Mouse IL-6 (1 microg) failed to alter core temperature after either intravenous
(i.v.) or i.p. administration. Human IL-6 was also ineffective. Recombinant mouse
tumor necrosis factor-alpha (mTNFalpha) also failed to alter the core temperature
of mice when injected at a dose of 1 microg (i.p. or i.v.). However, a higher
dose of mTNFalpha (5 microg i.p.) caused a short-lived decrease in Tc, followed
by a small increase. Similar results were obtained with LPS and the cytokines in
C57Bl/6J mice, except that mIL-1beta was ineffective in this strain. These
results indicate that the endocrine, neurochemical and behavioral responses to IL
1, IL-6 and TNFalpha administration cannot be explained by changes in Tc,
although they may contribute to them. They also suggest that IL-1beta may account
for the fever observed following LPS, but that these cytokines are probably not
the only factors involved in LPS-induced changes in Tc.
PMID- 9650816
TI - Granulocyte-macrophage colony stimulating factor suppresses LHRH release by
inhibition of nitric oxide synthase and stimulation of gamma-aminobutyric acid
release.
AB - Several cytokines produced by immune cells act within the hypothalamus and/or on
the pituitary to produce the pattern of pituitary hormone secretion that
characterizes infection. Granulocyte-macrophage colony stimulating factor (GMCSF)
was first described as a hematopoietic cytokine; however, its synthesis is also
stimulated during infection, and it has been found in glia in the brain. Previous
research indicates that interleukin-1 inhibits release of luteinizing hormone
releasing hormone (LHRH) both in vivo and in vitro. In the present study, we
determined that GMCSF inhibited the release of LHRH in vitro and evaluated the
mechanisms involved. After a 1-hour preincubation in Krebs-Ringer bicarbonate
glucose buffer (KRB), medial basal hypothalamic explants were incubated in KRB
together with recombinant murine GMCSF for 0.5 h in a Dubnoff metabolic shaker
(50 cycles/min) in an atmosphere of 95% O2/5% CO2. LHRH release into the media
was determined by radioimmunoassay. At concentrations of 10(-12) and 10(-11) M,
GMCSF significantly inhibited LHRH release. There was a U-shaped dose-response
curve and LHRH release was not inhibited at lower or higher cytokine
concentrations. The inhibition was specific since it was completely blocked by
GMCSF antiserum. Since sodium nitroprusside (NP; 300 microM), a releaser of
nitric oxide (NO), stimulates LHRH, presumably by acting within the LHRH neurons,
we examined the effect of GMCSF (10(-11) M) on NP-induced LHRH release. It
completely suppressed NP-induced release of LHRH. Bicuculline (10(-5) M), a gamma
aminobutyric acid (GABA) receptor antagonist, partially reversed the inhibitory
effects of GMCSF on LHRH release. This dose completely reversed the suppression
of LHRH release induced by GABA. The present results indicate that the inhibitory
effects of GMCSF on LHRH release are partially caused by blockade of NO-induced
LHRH release by its activation of GMCSF receptors on GABAergic neurons. The
stimulated release of GABA acts on the GABA-a receptors on the LHRH terminals to
inhibit their response to NO. At the end of the experiment, NO synthase (NOS)
activity was measured in the tissue homogenate by the citrulline method. NOS
activity was highly significantly reduced by GMCSF (10(-11) M) indicating that
part of its suppressive action on LHRH release is mediated by reduction in NOS
activity in the medial basal hypothalamus.
PMID- 9650817
TI - Stimulation of T-cell proliferation by pancreastatin and its C-terminal fragment
(33-49).
AB - We have studied the effect of pancreastatin and its C-terminal fragment (33-49)
on mitogen-stimulated T lymphocyte proliferation. In a concentration range from
10(-12) to 10(-8) M they exhibit a dose-dependent stimulatory effect on
concanavalin A-induced response with the maximal effect at 10(-8) M
concentration. They were inactive in response to a B-cell mitogen,
lipopolysaccharide, which points to an involvement of T but not B lymphocytes in
their response. Pancreastatin can still produce a stimulatory effect when added
18 h after incubation of cultures with concanavalin A and apparently uses a
diacylglycerol independent mechanism. When cells were preincubated for 4, 16 or
24 h with pancreastatin or its fragment and then stimulated with concanavalin A,
a ten times lower concentration of peptides was needed (10(-9) M) to obtain the
maximal response. This suggests that resting cells are more sensitive to
pancreastatin and its fragment. Both peptides exhibit a very similar
pharmacological profile, indicating that the C-terminal part of the molecule is
responsible for the effect on T-cell proliferation.
PMID- 9650818
TI - Direct morphological evidence of neuroimmunomodulation in colonic mucosa of
patients with Crohn's disease.
AB - Different neuropeptide-containing nerve fibers were investigated to clarify their
role in the pathogenesis of Crohn's disease (CD) using immunohisto- and
immunocytochemical techniques. Specimens were obtained from patients with CD from
grossly affected colonic regions, from biopsies obtained from patients with CD
treated with mesalazine and from control individuals. Quantitative analysis was
made for the changes of the number of nerve terminals and their vesicle contents.
The distribution pattern of all immunoreactive (IR) nerve fibers was similar both
in the control and in the surgical specimens as well as in the biopsies obtained.
The number of the synapses, the IR nerve fibers and their vesicle content were
markedly decreased in the grossly affected colonic regions. Some degenerated
axons were found in close proximity to the plasma cells. Immunocytochemistry
demonstrated that substance P, vasoactive intestinal polypeptide and somatostatin
IR nerve fibers were in direct contact with the plasma cells, lymphocytes and
other immunocompetent cells. The gap between the membranes of immunoreactive
nerve terminals and immunocompetent cells was 20-200 nm, in a few cases even
less. In the mesalazine-treated group the number of the IR nerve terminals as
well as their vesicle content was increased. These results suggest that changes
in the number of different neuropeptide-containing nerve terminals and their
content might alter the neuroimmunological processes, because these peptides are
known to be immunoregulators.
PMID- 9650819
TI - Administration of interleukin-1 into the hypothalamic paraventricular nucleus
induces febrile and behavioral effects.
AB - Administration of interleukin-1 (IL-1) into the cerebral ventricles produces
marked physiological and behavioral effects. However, the precise locations
within the central nervous system that mediate these effects have not been
determined. Previous studies indicated that IL-1 induces neurophysiological,
neurochemical and neuroendocrine changes within the hypothalamic paraventricular
nucleus (PVN). These findings suggest that the PVN is also involved in mediating
the behavioral effects of IL-1. This hypothesis was tested by examining the
effects of administration of IL-1beta (10 or 50 ng/rat) or saline, either
intracerebroventricularly or into the PVN, on fever and several behavioral
parameters. IL-1beta, administered into both locations, induced a comparable
suppression of motor activity, reduction in food and saccharine consumption, and
loss of body weight. The febrile response to IL-1beta, assessed by a
biotelemetric system, was significantly greater following administration into the
PVN than into the lateral ventricle. Additionally, IL-1 administration into
adjacent thalamic locations had no febrile or behavioral effects. These findings
suggest that the PVN may be one of the brain structures involved in mediating the
response to IL-1.
PMID- 9650820
TI - Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa.
AB - Mast cells degranulate when exposed to specific antigens (via surface bound IgE),
resulting in the release of numerous pro-inflammatory mediators. Neuroregulatory
substances also activate mast cells, and may effect differential mediator
release, without degranulation, suggesting a role for nerves in modulating mast
cell activity. We previously investigated the microanatomical relationships of
intestinal mucosal mast cells (IMMC) with nerves and found extensive associations
in the intestinal mucosae of rats and humans. The origins of nerves that contact
IMMC have not been determined; however, recent morphological and functional
studies suggest the possibility that the vagus nerve might be involved. In the
current study we show that vagal afferent fibers (labeled by injecting DiI into
the nodose ganglion) penetrate to the tips of jejunal villi; and that some of
these nerves make intimate contact with IMMC. These data provide the
microanatomical basis for direct neural communication between the central nervous
system (CNS) and mast cells in the gastrointestinal mucosa.
PMID- 9650821
TI - Centrally mediated inhibition of local inflammation by ciliary neurotrophic
factor.
AB - Since ciliary neurotrophic factor (CNTF) inhibits the production of TNF and
activates the hypothalamus-pituitary-adrenal axis (HPAA), we investigated whether
CNTF can produce antiinflammatory actions and whether it may act through a
central mechanism, using the murine air pouch model of inflammation. In this
model, inflammation is evaluated by measuring the induction of TNF and IL-6 as
well as cell recruitment in the pouch fluid 24 h after carrageenan.
Intracerebroventricular injection, but not intravenous or local injection of CNTF
markedly inhibited inflammation. This was associated with high serum
corticosterone levels, and antiinflammatory action was not observed in
adrenalectomized mice, indicating that an intact HPAA is required. A CNTF
receptor antagonist increased carrageenan inflammation, suggesting that
endogenous CNTF might have a centrally mediated antiinflammatory role.
PMID- 9650822
TI - Possible control of cell death pathways in ataxia telangiectasia. A case report.
AB - Peripheral blood monocytes (PBMCs) obtained from a boy with the
neuroimmunodegenerative syndrome of ataxia telangiectasia (AT) failed to
aggregate or replicate efficiently when mitogenically activated under serum
depleted conditions. These cells rapidly swelled, then slowly shrank, and
flattened as they excreted vesicles containing chromatin. This accelerated cell
death with loss of homoadhesiveness could be prevented in vitro in most of the
homozygous PBMCs by adding large amounts of autologous serum or by adding
mixtures of Th1 cytokines, serum factors, and redox agents. However, even in high
serum media containing added cytokines, 20-30% of the homozygous PBMCs quickly
flattened, produced minicells, and died. Since the defective functions of the
human ataxia-telangiectasia nuclear kinase gene (ATM) could be bypassed in vitro
in these defective AT PMBCs by addition of appropriate cytokines and redox
survival factors, it may be possible to slow the progressive losses of ATM
deficient lymphoid cells seen in vivo. Since the neuronal degeneration in AT, as
seen in the retrovirus-induced neuroimmunodegenerative syndromes, may also be a
consequence of impairment of the central and peripheral immune system, it may
become possible to prevent the neurodegeneration in AT by using signaling
therapies that upregulate the ATM-induced signal deficiencies in the developing
immune system.
PMID- 9650823
TI - Molecular biology of opioid receptors: recent advances.
AB - Endogenous opioid peptides and opiates like morphine produce their
pharmacological effects through the membrane bound opioid receptors. These
receptors belong to a superfamily of G-protein-coupled receptors, all of which
possess seven membrane-spanning regions. Structure-activity relationship studies
of opioids opened up new avenues for the pharmacological characterization of the
opioid receptors. As a further advancement in this direction, molecular cloning
has led to the identification of three different types of opioid receptors -- OP1
(delta), OP2 (kappa) and OP3 (mu) -- thereby supporting the results of earlier
pharmacological studies which postulated their existence. The three opioid
receptors are highly homologous. Consequent to the development of highly specific
and selective agonists and antagonists, it was proposed that the three types of
opioid receptors could be further categorized into different subtypes. However,
the molecular biology data generated so far do not support the presence of the
various subtypes of the three well-characterized opioid receptors. Recent strides
towards the advancement of our knowledge relating to the molecular biology of
these receptors have been reviewed in this article.
PMID- 9650824
TI - Afferent signals to the CNS appear not to condition the modulation of interleukin
1 receptors in the hippocampus.
AB - Conditioned alteration of natural killer (NK) cell activity was used as an
indicator of the functional bidirectional communication between the immune and
central nervous systems. Poly I:C and lipopolysaccharide (LPS) from Escherichia
coli and Salmonella typhimurium were used as unconditioned stimuli and odor of
camphor as the conditioned stimulus. An attempt was made to demonstrate the role
of central interleukin (IL-1) receptors in this communication process. Brain IL-1
receptors were down-regulated by treatment with 50 microg/mouse of LPS from S.
typhimurium, but not with the same dose of LPS from E. coli or poly I:C. A
significant level of conditioned augmentation of NK cell activity was observed
with poly I:C. Conditioned alteration in NK cell activity was also observed with
LPS from E. coli, but at much lower level than poly I:C. NK cell activity was not
conditioned with LPS from S. typhimurium at the same dose as E. coli LPS, but
conditioned enhancement of NK cell activity was observed with a higher dose (100
microg) of S. typhimurium LPS. These results suggest that modulation of central
IL-1 receptors do not seem to play a role in the conditioned augmentation of NK
cell activity.
PMID- 9650825
TI - Bradykinin receptors and their antagonists.
AB - Bradykinin and related kinins act on two receptor types, named B1 and B2.
Initially identified in classical bioassays, these receptors have been cloned and
characterized in binding assays performed on plasma membranes of cells expressing
the native or the transfected human kinin B1 or B2 receptor types. The two
classification criteria recommended by Schild, namely the order of potency of
agonists and the actual affinity of antagonists have been found to be applicable
for receptor classification based not on data only from bioassays but also from
other approaches (binding assays, molecular biology techniques). The order of
potency for agonists was found with naturally occurring peptides (the kinins,
their desArg9-metabolites) and with selective agonists (e.g., [Hyp3]bradykinin,
[Aib7]bradykinin): the findings obtained with agonists could be validated with
various antagonists. Critical evaluation of the initial compounds, typified by D)
Arg-[Hyp3, D-Phe7]bradykinin, has indicated that they are short-acting, partial
agonists, non-selective for the bradykinin B2 receptor because they can be
metabolized to desArg9-fragments that act on the kinin B1 receptor. Use of such
compounds has given rise to misunderstandings, especially with regard to new
receptor types (e.g., type B3), the existence of which was not confirmed by
molecular cloning. A second generation of antagonists, represented by D
Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (HOE 140) has been found resistant to
degradation, long-acting in vivo, selective and specific for the B2 receptor and
potent in all species tested. HOE 140 has been used successfully in basic
pharmacology, in animal physiopathologies involving kinins and their receptors
and even in clinical studies. A third generation of non-peptide B2 receptor
antagonists, whose prototype is FR 173657 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-2-4
dichloro-3-[(2-methyl-8-quinolin yl)oxymethyl]phenyl]-N-methylamino carbonyl
methyl]acrylamide) is now emerging and may represent substantial progress since
FR 173657 is a potent orally active, selective and specific antagonist of the
human and other species B2 receptors. There is also progress regarding
antagonists for the B1 receptor. The initial compounds, especially Lys
[Leu8]desArg9-bradykinin remain among of the most potent, specific and selective
B1 antagonists which, however, show partial agonistic effects in some B1 receptor
subtypes (e.g., the mouse). Progress has been made with AcLys-[D-betaNal7,
Ile8]desArg9-bradykinin (R 715) and Lys-Lys-[Hyp3, Cpg5, D-Tic7,Cpg8]desArg9
bradykinin (B 9958) which are pure B1 antagonists in humans and rabbits; both
peptides have shown resistance to degradation by peptidases and have little if
any, residual agonistic activity on mouse and rat B1 receptors. No non-peptide
antagonists are yet available for the B1 receptor.
PMID- 9650826
TI - Basal nitric oxide release differentially modulates vasodilations by pinacidil
and levcromakalim in goat coronary artery.
AB - In the current investigation, the role of basal nitric oxide (NO) in modulating
the vasorelaxant responses to pinacidil and levcromakalim was examined in goat
isolated coronary artery. Pinacidil (10(-8) 10(-4) M) elicited concentration
dependent relaxations of the coronary artery ring segments (with intact
endothelium) constricted with 30 mM K+ saline solution. The EC50 of the
vasodilator was 2.57 x 10(-6) M (95% CL, 1.9-3.46 x 10(-6) M). The removal of
endothelium by mechanical rubbing caused a rightward shift in the concentration
response curve of pinacidil with a corresponding increase in EC50 value (1.90 x
10(-5) M; 95% CL, 1.12-3.23 x 10(-5) M). Similar to endothelium removal,
treatment of endothelium-intact rings either with the NO synthesis inhibitor L
NAME (NG-nitro-L-arginine methyl ester; 3 x 10(-5) M) or the guanylate cyclase
inhibitor, methylene blue (3 x 10(-6) M) resulted in a marked inhibition in the
relaxant responses to pinacidil. Hence, the EC50 values of the potassium channel
opener were significantly higher in tissues treated either with L-NAME (7.41 x
10(-6) M; 95% CL, 6.02-9.12 x 10(-6) M) or methylene blue (2.29 x 10(-5) M; 95%
CL, 1.58-3.31 x 109-5) M) as compared to untreated controls. The ATP-sensitive
potassium (KATP) channel blocker glibenclamide, which caused a significant
rightward shift in the concentration-relaxation curve of pinacidil in control
tissues, was found to be less potent in antagonising the relaxant responses of
the KATP channel opener in endothelium-denuded rings and in rings with intact
endothelium but treated with either L-NAME or methylene blue. In contrast to the
observations made with pinacidil, the vasodilator responses to another KATP
channel opener, levcromakalim, were potentiated in the absence of basal NO. Thus,
the EC50 of levcromakalim was 1.33 x 10(-8) M (95% CL, 0.8-2.21 x 10(-8) M) in
control tissues with intact endothelium, which was significantly higher than
those obtained in endothelium-deprived rings (4.81 x 10(-9) M; 95% CL, 4.04-5.73
x 10(-9) M) or endothelium intact rings treated either with L-NAME (2.63 x 10(-9)
M; 95% CL, 1.58-4.36 x 10(-9) M) or methylene blue (2.82 x 10(-9) M; 95% CL, 1.7
4.68 x 10(-9) M). The selective modulation by basal NO of the arterial
relaxations elicited with the KATP channel openers was evident from the findings
that papaverine-induced relaxations were not affected in the absence of basal NO.
Taken together, the results of the present study suggest that basal NO
differentially modulates the interaction of pinacidil and levcromakalim with the
KATP channels in goat coronary artery through a cGMP-dependent pathway.
PMID- 9650827
TI - Interaction of endothelial eccrine mechanisms and human adrenomedullin on
vascular resistance in canine bone.
AB - Adrenomedullin is a novel peptide known to be one of the most potent vascular
smooth muscle relaxing agents in vivo. The aim of this study is to investigate
the effect of adrenomedullin in relation to nitric oxide, prostaglandins and
endothelium-derived hyperpolarized factor (EDHF). A 0.1-ml bolus of 1 nmol human
adrenomedullin is a potent inhibitor of the pressor response to exogenous
norepinephrine infusion in an ex vivo canine tibia perfusion model for a duration
of at least 70 min (P < 0.005). This attenuation of vascular smooth muscle
contraction occurs even when nitric oxide production is blocked by NG-monomethyl
L-arginine acetate (L-NMMA) infusion and EDHF is blocked by tetraethylammonium
infusion, although the effect is of shorter duration (at least 10 min).
Indomethacin as well does not affect the suppression of norepinephrine-induced
vascular smooth muscle contraction. Based on these data, human adrenomedullin has
both nitric oxide- and EDHF-dependent mechanism as well as a nitric oxide- and
EDHF-independent mechanism.
PMID- 9650828
TI - 5-hydroxydecanoate selectively reduces the initial increase in extracellular K+
in ischemic guinea-pig heart.
AB - The aim of the present study was to determine the effect of 5-hydroxydecanoate (5
HD) on extracellular K+ levels during global ischemia for 30 min employing K+
sensitive electrodes in isolated guinea-pig hearts. 5-HD (100 microM) reduced the
K+ accumulation during the early period of ischemia, but did not inhibit the
elevation of extracellular K+ in the latter half of the ischemic period which was
selectively enhanced by ouabain (3 microM). Thus, 5-HD appears to exert a similar
mode of action as glibenclamide on extracellular K+ accumulation in the ischemic
guinea-pig hearts. The present study also strengthens the previous conclusion
that an ATP-sensitive K+ channel contributes only to the initial increasing phase
of extracellular K+ accumulation during ischemia in guinea-pig hearts.
PMID- 9650829
TI - Effect of lipo-prostaglandin E1 on crescentic-type anti-glomerular basement
membrane nephritis in rats.
AB - The antinephritic effect of lipo-prostaglandin E1, prostaglandin E1 ((1R,2R,3R)-3
hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopent ane heptanoic acid)
incorporated in lipid microspheres was investigated using an experimental model
of nephritis, crescentic-type anti-glomerular basement membrane nephritis. Lipo
prostaglandin E1 was given i.v. twice a day at 20, 40 and 80 microg/kg and
azathioprine, an immunosuppressive agent, at 20 mg/kg was given p.o. once daily
from the autologous phase, in which glomerulonephritis was fully developed (the
21 st day after injection of the anti-glomerular basement membrane serum), to the
50th day. Lipo-prostaglandin E1 (40 and 80 microg/kg x 2 per day) significantly
inhibited the development of glomerular alterations as well as the elevation of
proteinuria and plasma creatinine. Lipo-prostaglandin E1 (20 microg/kg x 2 per
day) and azathioprine (20 mg/kg per day) significantly inhibited only the
glomerular histopathological changes. Lipo-prostaglandin E1 at three doses
significantly decreased the deposition of both rabbit immunoglobulin G and rat
immunoglobulin G on the glomerular basement membrane in nephritic rats, but
azathioprine apparently inhibited only the deposition of rat immunoglobulin G. A
single administration of lipo-prostaglandin E1 inhibited the elevation of
platelet aggregation and restored the decrease in renal tissue blood flow in
nephritic rats. In addition, a single administration of lipo-prostaglandin E1
inhibited the elevation of glomerular thromboxane B2 and 6-keto prostaglandin
F1alpha production in nephritic rats. These results suggest that lipo
prostaglandin E1 may be an effective agent for the treatment of
glomerulonephritis. Its antinephritic effect may be due to the inhibition of
platelet aggregation, an increase in renal tissue blood flow, a decrease in
rabbit and rat immunoglobulin G deposition, and amelioration of the abnormal
metabolism of arachidonic acid.
PMID- 9650830
TI - Antipyretic activity of cinnamyl derivatives and related compounds in influenza
virus-infected mice.
AB - Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic
activity by suppressing interleukin-1alpha production responsive to interferon in
a murine intranasal influenza virus infection model. Using this model,
antipyretic compounds with such novel biological activities were characterized
from the herbs. The organic solvent-extractable fractions of Cinnamomum cassia
among the herbs showed antipyretic activity. We selected six antipyretic
compounds from 48 cinnamyl derivatives and related compounds that may be mainly
involved in the fractions. Their antipyretic activity was significantly
correlated with interleukin-1alpha regulatory activity. Four of them suppressed
interleukin-1alpha production to a basal level and showed different mode of
antipyretic action from that of aspirin in interleukin-1alpha-injected mice.
Structure-bioactivity relationship of the four suggested that an ester bond
played an important role for both antipyretic and interleukin-1alpha regulatory
activities. These compounds may be useful in analyzing interleukin-1alpha
producing cells in fever production and the mechanism of defervescence by
suppressing interferon-induced interleukin-1alpha production.
PMID- 9650831
TI - Cyclic AMP accumulation in rat soleus muscle: stimulation by beta2- but not beta3
adrenoceptors.
AB - The beta-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus
muscle were studied using beta1- beta2- and beta3-adrenoceptor agonists and
antagonists. Responses to (-)-isoprenaline were antagonised by (-)-propranolol (p
KB = 8.32 at 0.1 microM) and by erythro-DL-1(7-methylindian-4-yloxy)-3
isopropylaminobuta n-2-ol (+/-)-ICI 118551) (pKB = 9.38 at 10 nM and 9.65 at 100
nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H
imidazole -2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate
((+/-)-CGP 20712A at 10 nM or 100 nM). The beta3-adrenoceptor agonist sodium-4-[
2[-2-hydroxy-2-(-3-chlorophenyl)ethylamino]propyl]phenoxya cetate (BRL 37344 at
10 pM or 10 microM) caused no significant change in basal cyclic AMP levels and
had no effect on the level of cyclic AMP accumulation stimulated by (-)
isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 microg
kg(-1) h(-1), 14 days) abolished responses to (-)-isoprenaline (10 microM) and
zinterol (1 microM) while BRL 37344 had no effect in either isoprenaline or
vehicle-treated groups. These results show that beta3-adrenoceptor agonists do
not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)
isoprenaline induced increases in cyclic AMP levels are mediated predominantly by
beta2-adrenoceptors. This suggests that the previously reported increase in
glucose uptake by beta3-adrenoceptor agonists in skeletal muscle does not involve
direct stimulation of adenylate cyclase.
PMID- 9650832
TI - The properties of caffeine- and carbachol-induced intracellular Ca2+ release in
mouse bladder smooth muscle cells.
AB - Freshly dissociated bladder smooth muscle cells of mice developed spontaneous,
caffeine- (ICAF) and carbachol-induced (ICCh) currents under voltage-clamped
conditions. Spontaneous currents, ICAF and ICCh were blocked with
tetraethylammonium at 3 x 10(-4)-10(-2) M but were resistant to both
charybdotoxin (10(-7)-10(-6) M) and iberiotoxin (10(-7)-10(-6) M). The reversal
potential for each current indicated that K+ channels play a major role in the
generation of each current. Both spontaneous currents and ICAF but not ICCh were
abolished in nominally Ca2+-free and nicardipine (10(-6) M)-containing media.
These results suggest that the activity of L-type voltage-sensitive Ca2+ channels
is important in the generation and maintenance of spontaneous currents and ICAF
but not ICCh. Ryanodine (10(-6) M) prevented spontaneous currents, ICAF and
caffeine-induced [Ca2+]i elevation but not ICCh and carbachol-induced [Ca2+]i
elevation, suggesting that the response of bladder smooth muscle cells to
carbachol may involve a Ca2+ store distinct from that for caffeine. Pretreatment
with carbachol suppressed ICAF to 22 +/- 7% (n = 7) and the caffeine-induced
[Ca2+]i elevation to 25 + 3% (n = 6). Similarly, caffeine suppressed ICCh to 23
+/- 4% (n = 9) and the carbachol-induced [Ca2+]i elevation to 24 +/- 6% (n = 6).
PMID- 9650833
TI - P2 receptor-mediated inhibition of adenylyl cyclase in PC12 cells.
AB - PC12 pheochromocytoma cells have P2 receptors which are coupled to Ca2+ influx
and catecholamine release. Previously we reported that ATP stimulated cyclic AMP
accumulation at low concentrations up to 100 microM but showed inhibitory effects
above this concentration [Yakushi, Y., Watanabe. A.. Murayama, T., Nomura, Y.,
1996. Eur. J. Pharmacol. (314) 243-248]. In this study we investigated the
characteristics of the inhibitory effects of ATP analogs. In the presence of 10
microM forskolin, an activator of adenylyl cyclase, ATP, adenosine 5'-O-(3
thiotriphosphate) (ATPgammaS), 2',3'-O-(4-benzoyl) benzoyl ATP, 2-methylthio ATP
and adenosine 5'-O-(2-thiodiphosphate) inhibited cyclic AMP accumulation in a
dose-dependent manner from 100 microM. UTP, alphabeta and betagamma-methylene ATP
had no or very limited effects. The relative order of ATP analogs suggests that
the ATP receptor appears to be P2Y-like. However, suramin, an antagonist of P2X
and P2Y receptors, and reactive blue-2, which inhibited betagamma-methylene ATP
induced cyclic AMP accumulation, did not modify the inhibitory effect of
ATPgammaS. Treatment with pertussis toxin, which completely abolished the effect
of carbachol, had no effect on the action of ATP over 300 microM. The existence
of a new type of ATP receptor-mediated inhibition of adenylyl cyclase is proposed
in PC12 cells.
PMID- 9650834
TI - Structural significance of azaheterocyclic amines related to Parkinson's disease
for dopamine transporter.
AB - We have evaluated the neuronal uptake of 12 neutral and quaternary
azaheterocyclic amines that are possible candidates for idiopathic Parkinson's
disease via dopamine transporter of striatal synaptosomes. The double-reciprocal
plots for dopamine transporter obtained from Wistar rat and C57BL/6 mouse
synaptosomes with N-methyl-4-phenylpyridinium cation (MPP+) as a substrate were
identical to each other. Neutral beta-carbolines and tetrahydroisoquinolines were
unfavorable substrates for dopamine transporter. The quarternization of these
compounds strikingly increased the affinity for dopamine transporter with 2-10
times greater Km and 10 times smaller Vmax values than MPP+. Although catechol
tetrahydroisoquinolines were weak substrates, their quarternization reduced their
original properties as substrates for dopamine transporter. These results provide
both topographic and electrogenic information of azaheterocyclic amines for the
dopamine transporter-mediated influx. The intramolecular distance between the N
atom and the centroid of the benzene ring could be an important factor for the
recognition of binding site of dopamine transporter, and an adequate net charge
similar to dopamine would be further required for translocation into the cells.
PMID- 9650835
TI - Catecholaminergic CATH.a cells express predominantly delta-opioid receptors.
AB - CATH.a cells are a catecholaminergic cell line of neuronal origin. The opioid
receptor complement expressed by CATH.a cells was defined pharmacologically and
by reverse transcription-polymerase chain reaction (RT-PCR). CATH.a cells were
found to express mRNA encoding all three of the major subtypes of opioid
receptors. The relative abundance of CATH.a cell opioid receptor transcripts was
delta > kappa> mu. Pharmacological and functional data were in agreement with the
results of RT-PCR inasmuch as delta-opioid receptor was identified as the most
abundant opioid receptor subtype expressed by CATH.a cells. In addition, at least
one of the opioid signalling pathways, inhibition of adenylyl cyclase activity,
was found to be operant in this cell line. CATH.a cells should be of general
utility for the study of opioid receptor signalling mechanisms in the context of
catecholaminergic neurons.
PMID- 9650836
TI - Vasoactive intestinal peptide modification at position 22 allows discrimination
between receptor subtypes.
AB - Secretin and growth hormone releasing factor (GRF) have a weak affinity for VIP
(vasoactive intestinal peptide)/PACAP (pituitary adenylate cyclase activating
polypeptide) receptors, but discriminate between VIP1/PACAP and VIP2/PACAP
receptors. This previously allowed us to develop modified secretin and GRF
derivatives as high affinity and highly selective VIP1/PACAP receptor ligands. We
tested the hypothesis that the presence of a Gln residue at position 24 and a Leu
residue at position 22 was responsible for their VIP1/PACAP receptor selectivity.
[Gln24]VIP was not different from VIP but [Leu22]VIP had a 100-fold lower
affinity for VIP2/PACAP receptors as compared to VIP1/PACAP receptors. The
substitution of Tyr22 by Phe22 in VIP had no significant effect on the
recognition of both receptors but [Ala22]VIP had a reduced affinity for the
VIP2/PACAP receptor. This indicated that an aromatic residue at position 22 of
VIP was required for a high affinity for the VIP2/PACAP receptor but not for the
VIP1/PACAP receptor.
PMID- 9650837
TI - Characterization and distribution of angiotensin II receptor subtypes in the
mouse brain.
AB - We localized and characterized angiotensin II receptor subtypes (AT1 and AT2) in
the mouse brain, with the use of autoradiography after incubation with
[l25I][Sar1]-angiotensin II or [125I]CGP 42112 and displacement with selective
angiotensin AT1 (losartan and candesartan) or angiotensin AT2 (CGP 42112(1) and
PD 123319(2)) receptor ligands. In the mouse, the receptor subtype affinity for
the different ligands was similar to that of the rat. The receptor subtype
distribution was also similar to that in the rat, with some notable exceptions,
such as the presence of angiotensin AT1 but not AT2 receptors in the locus
coeruleus, and the expression of angiotensin AT1 receptors in the caudate
putamen. These results confirm that careful consideration of the specific
distribution of receptor subtypes in different species, even those closely
related such as the mouse and the rat, should be conducted before meaningful
comparisons could be proposed. Our data also form the basis for future studies of
mouse models such as those with angiotensin receptor gene deficiencies.
PMID- 9650838
TI - Dose-related inversion of cinnarizine and flunarizine effects on mitochondrial
permeability transition.
AB - We investigated the effects of cinnarizine and flunarizine on mitochondrial
permeability transition, ATP synthesis, membrane potential and NAD(P)H oxidation.
Both drugs were effective in inhibiting the mitochondrial permeability transition
induced either by Ca2+ alone or in the presence of tert-butylhydroperoxide. This
protective effect occurred at low concentrations (< 50 microM) of these drugs and
was accompanied by the inhibition of NAD(P)H oxidation and the restoration of the
mitochondrial membrane potential decreased by a high concentration of Ca2+ (25
microM). However, at higher concentrations (> 50 microM) of cinnarizine and
flunarizine and in the absence of both tert-butylhydroperoxide and Ca2+, their
effects on the mitochondria were reversed as follows: mitochondrial permeability
transition was generated, mitochondrial NAD(P)H was oxidized and membrane
potential collapsed. These deleterious effects were not antagonized by
cyclosporine A, the most potent inhibitor of the mitochondrial permeability
transition, but by 2,6-di-tert-butyl-4-methylphenol, a known antioxidant agent.
This mitochondrial effect was neither accompanied by an increase in
malondialdehyde production nor by an increase in H2O2 generation, which attested
that the effect of both drugs was not due to an increase in reactive oxygen
species production. The dual effects of both cinnarizine and flunarizine on
mitochondrial functions is discussed with regard to both the protective effect
afforded by these drugs against ischemia-reperfusion injury and their side effect
observed in some therapeutic situations where an overdosage seems likely.
PMID- 9650839
TI - An agonist-like monoclonal antibody against the human beta2-adrenoceptor.
AB - Monoclonal antibodies were produced against a peptide corresponding to the second
extracellular loop of the human beta2-adrenoceptor. One of these monoclonals,
inducing an agonist-like effect in neonatal rat cardiomyocytes, was used to
define the structural and physiological basis of this activity. The epitope
recognized by the antibody corresponds to the sequence Trp-Tyr-Arg-Ala-Thr-His
Gln-Glu as determined by peptide scanning. Analysis by alanine modification of
the peptide epitope showed the importance of the Trp, and Glu residues in
antibody recognition The apparent affinity of the antibody assessed either by
surface plasmon resonance or by functional titration on its agonist-like activity
showed a similar value (10(8) M(-1)). The antibody recognized the receptor in its
native form as shown by immunofluorescence experiments on A431 cells but not in
its denatured form as shown by its absence of staining in immunoblots. The
positive chronotropic effect in vitro was specifically blocked by both the
antigenic peptide and the specific beta2-antagonist (+/-)-1-[2,3-(Dihydro-7
methyl1H-inden-4-yl)oxy]-3-[(1-methy lethyl)amino]-2-butanol hydrochloride
(ICI1118,551). This activity was mediated through activation of Ca2+ L-type
channels as assessed in guinea pig cardiomyocytes. These results suggest that the
epitope is located in an extracellular alpha-helix, whose recognition by the
antibody could stabilize the receptor in its 'active' conformation.
PMID- 9650840
TI - Concomitant regulation of Ca2+ mobilization and G13 expression in human
erythroleukemia cells.
AB - In human erythroleukemia (HEL) cells, stimulation of alpha2-adrenoceptors by
adrenaline or neuropeptide Y Y1 receptors by neuropeptide Y, concomitantly
inhibit cAMP accumulation and stimulate mobilization of Ca2+ from intracellular
stores via pertussis toxin-sensitive G-proteins. Treatment of HEL cells in
chemically-defined, serum-free medium with 1.25% dimethylsulfoxide (DMSO) for 4
days, increased alpha2-adrenoceptor number by 120%, while the neuropeptide Y
receptor number was not significantly changed. In DMSO-treated HEL cells, Ca2+
elevations by adrenaline or neuropeptide Y were significantly reduced by 28% and
57%, respectively, while basal Ca2+ and elevations by thrombin or thapsigargin
were not significantly altered. Adrenaline and neuropeptide Y-induced inhibition
of forskolin-stimulated cAMP accumulation was not significantly altered upon DMSO
treatment. While immunodetectable alpha-subunits of Gi2 were not significantly
changed by DMSO treatment, those of Gi3 were reduced by 27%. Inactivation of
pertussis toxin substrates by pertussis toxin treatment and inhibition of
adrenaline or neuropeptide Y stimulated Ca2+ elevations were linearly correlated.
These data are compatible with the idea that, in HEL cells, alpha2-adrenoceptors
and neuropeptide Y receptors couple to inhibition of adenylyl cyclase via Gi2
while they couple to Ca2+ elevations via Gi3.
PMID- 9650841
TI - Potent effects of a selective cannabinoid receptor agonist on some guinea pig
medial vestibular nucleus neurons.
AB - Binding studies have indicated that the density of the cannabinoid CB, receptor
is very low in the vestibular nucleus complex compared to other areas of the
central nervous system (CNS), suggesting that CB1 receptors may have little
functional significance for the vestibular nucleus. However, the dizziness often
produced by cannabis suggests that the vestibular system may be implicated. We
investigated the effects of the selective CB1 receptor agonist, CP 55940 (the
levorotatory enantiomer of desacetyllevonantradol), on medial vestibular nucleus
neurons in guinea pig brainstem slices in vitro. Only 3/18 medial vestibular
nucleus neurons tested with 1 microM CP 55940 showed changes in firing rate,
however these were decreases with an average magnitude of 72.3%; 3/4 neurons
tested with 10 microM CP 55940 showed decreases with an average magnitude of
92.7% (P < 0.05 in both cases). In all cases the effects of CP 55940 were long
lasting. These results suggest that despite the low density of CB1 receptors in
the vestibular nucleus complex, they may be of functional significance for the
behavioural effects of cannabis use.
PMID- 9650842
TI - Adenosine receptor activation and nociception.
AB - Adenosine and ATP exert multiple influences on pain transmission at peripheral
and spinal sites. At peripheral nerve terminals in rodents, adenosine A1 receptor
activation produces antinociception by decreasing, while adenosine A1 receptor
activation produces pronociceptive or pain enhancing properties by increasing,
cyclic AMP levels in the sensory nerve terminal. Adenosine A3 receptor activation
produces pain behaviours due to the release of histamine and 5-hydroxytryptamine
from mast cells and subsequent actions on the sensory nerve terminal. In humans,
the peripheral administration of adenosine produces pain responses resembling
that generated under ischemic conditions and the local release of adenosine may
contribute to ischemic pain. In the spinal cord, adenosine A receptor activation
produces antinociceptive properties in acute nociceptive, inflammatory and
neuropathic pain tests. This is seen at doses lower than those which produce
motor effects. Antinociception results from the inhibition of intrinsic neurons
by an increase in K+ conductance and presynaptic inhibition of sensory nerve
terminals to inhibit the release of substance P and perhaps glutamate. There are
observations suggesting some involvement of spinal adenosine A2 receptors in pain
processing, but no data on any adenosine A3 receptor involvement. Endogenous
adenosine systems contribute to antinociceptive properties of caffeine, opioids,
noradrenaline, 5-hydroxytryptamine, tricyclic antidepressants and transcutaneous
electrical nerve stimulation. Purinergic systems exhibit a significant potential
for development as therapeutic agents. An understanding of the contribution of
adenosine to pain processing is important for understanding how caffeine produces
adjuvant analgesic properties in some situations, but might interfere with the
optimal benefit to be derived from others.
PMID- 9650843
TI - Apamin improves spatial navigation in medial septal-lesioned mice.
AB - We investigated the effects of acute i.p. injections of the Ca2+-dependent K+
channel blocker, apamin, on water maze spatial navigation, Y-maze and passive
avoidance behavior in intact and medial septal-lesioned mice. Apamin 0.02, 0.06
or 0.2 mg/kg (i.p.) administered 30 min before or immediately after the training
did not affect the performance of intact mice. Apamin 0.02 or 0.06 mg/kg (i.p.)
administered immediately after the daily training did not affect the performance
of medial septal-lesioned mice. Apamin 0.02 and 0.06 mg/kg (i.p.) administered 30
min before daily training reversed the navigation failure present in medial
septal-lesioned mice during the initial and reversal learning stages of the water
maze task. Apamin had no effect on the cognitive performance in Y-maze or passive
avoidance tests. The results indicate that blockade of Ca2+-dependent K+ channels
may facilitate acquisition of spatial navigation performance, but has no effect
on consolidation, inhibitory avoidance and spontaneous alternation behavior in
mice.
PMID- 9650844
TI - The effect of oxcarbazepine on behavioural despair and learned helplessness.
AB - The effect of oxcarbazepine was evaluated in two tests of depression (forced
swimming and learned helplessness) and in the open-field test. Acute (three times
over 24 h) oxcarbazepine 80 mg/kg (but not 40 mg/kg) decreased immobility time in
the forced swimming test. In the learned helplessness test, 4 days of treatment
with oxcarbazepine 80 mg/kg reversed the deficits induced by foot-shock in rats
submitted to the two-way active avoidance test. Oxcarbazepine 80 mg/kg did not
modify the behaviour of rats in the open-field test, an indication that, at this
dose, oxcarbazepine did not show a locomotor stimulatory effect. Thus, the data
of the present study suggest that oxcarbazepine has a potential antidepressive
effect.
PMID- 9650845
TI - Facilitation of cognitive functions by a specific alpha2-adrenoceptor antagonist,
atipamezole.
AB - The present experiments investigated the effects of a specific and potent alpha2
adrenoceptor antagonist, atipamezole (as a stimulator of the noradrenergic
system) on cognitive performance in rats. Atipamezole enhanced the acquisition of
a linear-arm maze test and also improved the choice accuracy of poorly performing
rats in a delayed (20 min) three-choice maze test. Furthermore, atipamezole
improved the achievement of a one-trial appetite-maze when injected immediately
after teaching, thus having an effect on consolidation. Atipamezole clearly
impaired the acquisition of the active avoidance test. The present results
indicate that stimulation of noradrenergic system by atipamezole improves the
performance of animals in tasks assessing relational learning and memory,
possibly affecting attention, short-term memory and the speed of information
processing. It has also an effect on a consolidation process unrelated to
attentional or motivational mechanisms. In a stressful test. stimulation of
noradrenaline release leads to impairment of performance.
PMID- 9650846
TI - Effects of WAY 100635 and (-)-5-Me-8-OH-DPAT, a novel 5-HT1A receptor antagonist,
on 8-OH-DPAT responses.
AB - The neurochemical profile at both post and presynaptic 5-HT1A receptors of a
novel 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) analog, 5-methyl-8
hydroxy-2-(di-n-propylamino)tetralin ?(+/-)-5-Me-8-OH-DPAT? and its stereoisomers
was determined and compared to that of the highly selective 5-HT1A receptor
antagonist, N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl) cyclo
hexanecarboxamide (WAY 100635). We evaluated their effects on 8-OH-DPAT-induced
decrease in cAMP production, on 8-OH-DPAT-induced decrease in rat ventral
hippocampal extracellular 5-hydroxytryptamine (5-HText) levels and in body
temperature in mice. Both (+/-)- and (-)-5-Me-8-OH-DPAT blocked the 8-OH-DPAT
induced inhibition of forskolin-stimulated cAMP production. Moreover, while
having no significant effect when injected alone, (+/-)-, (-)-5-Me-8-OH-DPAT and
WAY 100635 antagonized the 8-OH-DPAT-induced decrease in 5-HText in rats and
hypothermia in mice. By contrast, the (+) isomer inhibited the cAMP synthesis and
did not modify the 8-OH-DPAT response on 5-HText in ventral hippocampus. These
data suggest that (+/-)-5-Me-8-OH-DPAT acts selectively, its activity residing in
the (-) enantiomer, this latter compound acting similarly to WAY 100635 as a
full, selective and silent 5-HT1A antagonist.
PMID- 9650847
TI - 5-Hydroxytryptophan-induced myoclonus in guinea pigs: mediation through 5-HT1/2
receptor subtypes.
AB - In guinea pigs, myoclonus can be induced by 5-hydroxytryptamine (5-HT, serotonin)
precursors and synthetic 5-HT receptor agonists, yet the receptor subtype
specificity of this behavior is not fully delineated. Guinea pigs were pre
treated with carbidopa (50 mg) followed by one of eight 5-HT antagonists: (-)-N
tert-butyl-3-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenyl propionamide ((-)-WAY
100135) (5-HT1A), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridyl)
cy clohexancarboxamide (WAY 100635) (5-HT1A), methiothepin mesylate (5-HT1/2),
mesulergine hydrochloride (5-HT2A/2C), N[4-methoxy-3-(4-methyl-L
piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2 ,4-oxadizol-3-yl) (GR 127935) (5
HT1D), trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-fluorop hen yl) propen-1
yl]phenol, hemifumarate (SR 46349) (5-HT2), ondansetron hydrochloride (5-HT3),
and [1-[2-[methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-meth oxy
1H-indole-3-carboxylate (GR 125487) (5-HT4). Thirty minutes later, they received
5-hydroxytryptophan (5-HTP) (75 mg/kg, sc) and myoclonic jumping rates were
assessed every 10 min for 200 min by a blinded observer. Repeated measures
analysis of variance of drug-induced antagonism of 5-HTP-induced myoclonus
revealed a significant effect for the 5-HT receptor antagonists methiothepin
mesylate, GR127935, and mesulergine hydrochloride compared to placebo, and each
of these drugs inhibited 5-HTP-induced myoclonus in a dose-dependent fashion.
Based on the receptor profiles of the three effective antagonists, 5-HTP-induced
myoclonus is influenced by the 5-HT1/2 receptor systems. The absence of a
significant change with any other receptor subtype antagonist suggests that
myoclonus is not related to diffuse activation of central serotonergic
mechanisms.
PMID- 9650848
TI - Pharmacologic restoration of suppressed temperature rhythms in rats by melatonin,
melatonin receptor agonist, S20242, or 8-OH-DPAT.
AB - Endogenous circadian rhythms in body temperature and locomotor activity rhythms
are suppressed in Sprague-Dawley rats exposed to prolonged continuous light,
possibly as a result of a profound alteration of the melatonin secretion rhythm.
The ability to restore circadian system function with either exogenous melatonin,
or melatonin receptor agonist S20242 (N-[2-(7-methoxy napth-1-yl)ethyl]
propionamide), or 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin
(8-OH-DPAT), was investigated under these conditions. Seven rats received a daily
6-h intravenous infusion of melatonin (0.01 mg kg(-1)) for 10 days, which
generates a nearly physiological circadian rhythm of urinary 6-sulfatoxy
melatonin, the main urinary metabolite of melatonin. Nevertheless, there was no
effect on body temperature or locomotor activity rhythms. Then, 49 rats received
daily subcutaneous melatonin (0.01, 1 or 5 mg kg(-1) day(-1)), S20242 (1 or 5 mg
kg(-1) day(-1)) or 8-OH-DPAT (5 mg kg(-1) day(-1)) for 30 days. The circadian
rhythm in body temperature was restored by subcutaneous melatonin or by S20242 as
a function of the dose or by 8-OH-DPAT. The effect started within the first 10
days of treatment and persisted for I to 3 weeks following the end of treatment
in 8 of 10 rats receiving melatonin, in 9 of 11 rats treated with S20242 and in 1
of 4 rats treated with 8-OH-DPAT. Activity was less susceptible to entrainment
than temperature with these drugs, since circadian rhythmicity was restored in
only 2 of 6 rats treated with melatonin and in 1 of 4 rats treated with 8-OH
DPAT. These data demonstrate a specific action of subcutaneous melatonin, S20242
or 8-OH-DPAT on temperature rather than on activity rhythms. This differential
effect on two major outputs of the suprachiasmatic nucleus further supports the
existence of two independent oscillators in this hypothalamic circadian clock,
which may be considered as separate pharmacological targets in the circadian
system.
PMID- 9650849
TI - Dexamethasone augments ischemia-induced extracellular accumulation of glutamate
in gerbil hippocampus.
AB - Glucocorticoids exacerbate neuronal damage due to hypoxia, ischemia, seizure and
hypoglycemia. Because the release of glutamate is closely involved in neuronal
damage, the effects of dexamethasone on the ischemia-induced accumulation of
extracellular amino acids (aspartate, glutamate, and glycine) were investigated
in the gerbil hippocampal CA1 region by a microdialysis-high-performance liquid
chromatography procedure in vivo. There were no differences in the extracellular
concentrations of amino acids before ischemia between the control group and the
dexamethasone (3m microg, i.c.v.)-injected group. The concentration of glutamate
reached 246% of that before ischemia within 2.5 min of transient forebrain
ischemia. Dexamethasone augmented the increase in glutamate to 508% of that
before ischemia. This finding suggests that glucocorticoids aggravate ischemic
neuronal damage by causing glutamate to accumulate in the extracellular space.
PMID- 9650850
TI - Depressor responses to endothelin-1 into the superior colliculus of rats:
predominant role of endothelin ET(B) receptors.
AB - We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s)
in the superficial gray layer of the superior colliculus of rats. These studies
showed dense binding of (3-[125I]iodotyrosyl13)-[Ala11,15]Ac-endothelin-1-(6-2 1)
(BQ3020) (for endothelin ETB receptors), while tissues incubated with [125I]( N
(hexahydro-1-azepinyl)carbonyl)L-Leu(1-Me)D-Trp-D-Tyr (PD151242) (for endothelin
ETA receptors) had low binding. In addition, we examined the effects of the
endothelin receptor antagonists, (R)-2-[(R)-2-[(S)-2-[[1-hexahydro-1H
azepinyl)]carbonyl]amino-4-++ +methylpentanoyl]-amino-3-(2-pyridyl)propionic acid
(FR139317) (endothelin ETA receptor-selective), (+)-(1S,2R,3S)-3-(2
carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenediox yphenyl)-5-(prop-1
yloxy)indane-2-carboxylic acid (SB209670) (endothelin ETA/ETB receptor non
selective) and N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-metLeu-D-1-m
ethoxycarbonylTrp-D-Nle (BQ-788) (endothelin ETB receptor-selective antagonist)
on the responses following administration of endothelin-1 into the superficial
layer of the superior colliculus. Endothelin-1 microinjected into this nucleus
causes decreases in blood pressure (control, 109 +/- 6 mmHg, n = 6; endothelin-1,
72 +/- 5 mmHg, n = 6). These effects were greatly reduced by pre-administration
into the superior colliculus of BQ-788 (5 nmol/rat) or SB209670 (3 nmol/rat) (94
+/- 5 and 98 +/- 6%, respectively) but were not affected by FR139317 (5 nmol/rat)
(6 +/- 3%). Therefore, together with autoradiography, our functional data showed
that endothelin ETB receptors are the predominant mediators of depressor
responses induced by endothelin-1 injected into the superior colliculus of the
rat.
PMID- 9650851
TI - Effect of the gastrin-releasing peptide antagonist BIM 26226 and lanreotide on an
acinar pancreatic carcinoma.
AB - The effects of a potent specific gastrin-releasing peptide receptor antagonist,
BIM 26226 ([D-F5 Phe6, D-Ala11] bombesin (6-13) OMe), and the long-acting
somatostatin analogue, lanreotide (BIM 23014), on the growth of an acinar
pancreatic adenocarcinoma growing in the rat or cultured in vitro were
investigated. Lewis rats bearing a pancreatic carcinoma transplanted s.c. in the
scapular region, were treated with gastrin-releasing peptide (30 microg/kg per
day), BIM 26226 (30 and 100 microg/kg per day) and lanreotide (100 microg/kg per
day) alone or in combination for 14 successive days. Chronic administration of
BIM 26226 and lanreotide significantly inhibited the growth of pancreatic tumours
stimulated or not by gastrin-releasing peptide (GRP), as shown by a reduction in
tumour volume, protein, ribonucleic acid, amylase and chymotrypsin contents. This
effect was more pronounced with 100 microg/kg per day BIM 26226 than with 30
microg/kg per day. However, BIM 26226 and lanreotide, given together, did not
exert any additive effect on GRP-treated and -untreated tumours. In cell
cultures, both BIM 26226 and lanreotide (10(-6) M) inhibited [3H]thymidine
incorporation in tumour cells induced or not by GRP, but no increased effect was
observed after combined treatment with both agents. Binding studies showed that
BIM 26226 had a high affinity for GRP receptors in tumour cell membranes (IC50 =
6 nM). These results from in vivo and in vitro experiments suggest that BIM 26226
and lanreotide are able to reduce the growth of an experimental acinar pancreatic
tumour. Thus, these agents represent interesting steps toward the development of
new approaches for treatment of pancreatic carcinomas.
PMID- 9650852
TI - Comparison of cyclooxygenase-1 and -2 inhibitory activities of various
nonsteroidal anti-inflammatory drugs using human platelets and synovial cells.
AB - Recent studies have shown that cyclooxygenase exists in two isozyme forms. Since
differences in the pharmacological profiles of nonsteroidal anti-inflammatory
drugs (NSAIDs) might be accounted for by varying degrees of selectivity for these
isozymes, cyclooxygenase-1 and -2, the relative potency of various NSAIDs in
inhibiting their activities was examined in intact human cells. We used human
platelets cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell
cyclooxygenase-2 for measuring cyclooxygenase selectivity. The presence of the
enzymes was confirmed by immunoblotting and immunoprecipitation analysis, and by
the reverse transcriptase-polymerase chain reaction. Mean IC50 values (microM)
for human platelet cyclooxygenase-1 and interleukin-1beta-stimulated human
synovial cell cyclooxygenase-2 and cyclooxygenase-1/-2 IC50 ratio of various
NSAIDs were as follows: aspirin, 3.2, 26, 0.12; diclofenac, 0.037, 0.00097, 38;
etodolac, 122, 0.68, 179; ibuprofen, 3.0, 3.5, 0.86; indomethacin, 0.013, 0.044,
0.30; loxoprofen (active metabolite), 0.38, 0.12, 3.2; NS-398, 12, 0.0095, 1263;
oxaprozin, 2.2, 36, 0.061; zaltoprofen, 1.3, 0.34, 3.8; respectively. Our
bioassay system employing intact human cells to assess the cyclooxygenase
selectivity of NSAIDs may provide clinically useful information.
PMID- 9650853
TI - Immunologic action of [Met5]enkephalin fragments.
AB - The aim of this study was to evaluate the effects of [Met5]enkephalin, des-Met
[Met5]enkephalin, des-Tyr-[Met5]enkephalin, and Tyr-Gly-Gly on natural killer
cytotoxic activity and on concanavalin A- and lipopolysaccharide-stimulated
proliferation of B and T cells in mice. Single i.p. injections of
[Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased both
natural killer cytotoxicity and proliferation of mitogen-stimulated B and T
cells. These effects were inhibited by naloxone pretreatment, which suggests the
opioid mechanism of the peptides studied. The rate of lymphocytic proliferation
increases not only after single injection of [Met5]enkephalin or its metabolites,
but also after 3 or 7 days of treatment. Apart from the functional effects,
[Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased the
percentages of natural killer cells and T cells. The results of this study
suggest that the immunomodulatory action of [Met5]enkephalin may be mediated or
enhanced by its N-terminal metabolites des-Met-[Met5]enkephalin and Tyr-Gly-Gly.
PMID- 9650854
TI - Inhibition of nociceptin on sensory neuropeptide release and mast cell-mediated
plasma extravasation in rats.
AB - Nociceptin (20 microg/kg i.p.) strongly inhibited cutaneous Evans blue
accumulation in the chronically denervated hindpaw of the rat in response to mast
cell degranulating peptide (MCDP, 0.25 microg in 100 microl) but it had no and
marginal effect on plasma extravasation induced by 5-hydroxytryptamine (5-HT, 0.5
microg in 100 microl) and histamine (0.1 microg in 100 microl), respectively.
Release of sensory neuropeptides such as substance P, calcitonin gene-related
peptide (CGRP) and somatostatin from the rat isolated trachea in response to
capsaicin (10(-8) M) or bradykinin (10(-7) M) were also attenuated by nociceptin
(100 and 300 nM). It is concluded that chemically induced discharge of mediators
from mast cells and from capsaicin-sensitive afferent nerve terminals are both
inhibited by nociceptin that participates in the anti-inflammatory effect of the
peptide.
PMID- 9650855
TI - Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells.
AB - A morphine alkaloid derivative, buprenorphine hydrochloride, induces apoptosis in
NG108-15 cells. Apoptosis was detected mainly by apoptosis-specific DNA
fragmentation and morphological changes. This apoptosis was dose-dependent and
the time-course experiment indicated that DNA fragmentation occurred within 4 h
after administration of buprenorphine hydrochloride. Specific inhibitors of the
previously characterized apoptotic signal cascade as well as antagonists for
opioid receptors were tested. Zn2+, herbimycin A, caspase inhibitors YVAD (Ac-Tyr
Val-Ala-Asp-CHO) and DEVD (Ac-Asp-Glu-Val-Asp-CHO), naloxone and naltrindole had
no effect on apoptosis-specific DNA fragmentation. The serine protease inhibitor
TPCK (N-tosyl-L-phenylalanyl chloromethyl ketone) specifically inhibited
apoptosis-specific DNA fragmentation induced by buprenorphine hydrochloride;
however, cell viability measurements revealed that cell death still occurred in
NG108-15 cells. Thus TPCK pretreatment before buprenorphine hydrochloride
administration induced apoptosis-independent cell death, presumably necrosis, in
NG108-15 cells. This suggests that an unidentified serine protease, presumably
functioning in the buprenorphine hydrochloride-specific death-signal cascade,
could be pivotal for the rapid apoptosis observed in NG108-15 cells upon
treatment with buprenorphine hydrochloride.
PMID- 9650856
TI - Functional interactions of L-162,313 with angiotensin II receptor subtypes and
mutants.
AB - A nonpeptide ligand, L-162,313 (5,7-dimethyl-2-ethyl-3-[[4-[2(n
butyloxycarbonylsulfonamido)-5-is obutyl-3
thienyl]phenyl]methyl]imidazo[4,5,6]pyridine) was characterized on the
angiotensin II receptors. This compound displaced [125I][Sar1]angiotensin II from
rat angiotensin AT1A, AT1B or AT2 receptor individually expressed in COS-7 cells
(Ki = 207 nM, 226 nM and 276 nM, respectively). In monkey kidney cells expressing
angiotensin AT1A or AT1B receptors, it stimulated inositol phosphate
accumulation, but the maximal response was 34.9 and 23.3%, respectively, of those
of angiotensin II. Furthermore, an antagonist effect of L-162.313 was observed in
response to angiotensin II. Single-point substitutions in the second and third
transmembrane domains of the rat angiotensin AT1A receptor, which impaired the
binding of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1[(1H-tetrazol-5
yl)biphenyl-4 -yl)methyl]imidazole), also affected the binding of L-162,313.
Losartan and L-162,313 require some common structural determinants for non
peptide recognition on the angiotensin AT1 receptor. Furthermore, some of these
substitutions, which impaired the inositol phosphate accumulation in response to
angiotensin II, also impaired the response to L-162,313. Angiotensin II and L
162,313 require common critical residues for angiotensin AT1 receptor activation.
PMID- 9650857
TI - The electrophysiological effects of tetraphenylphosphonium on vascular smooth
muscle.
AB - The effect of the lipophilic quaternary ion, tetraphenylphosphonium, on membrane
potential of segments of rat small mesenteric artery and on the current in single
voltage-clamped smooth muscle cells from rabbit portal vein was studied. In rat
small mesenteric artery, tetraphenylphosphonium (1-30 microM) caused membrane
depolarization of approximately 23 mV and decreased or abolished the
hyperpolarization induced by the KATP channel opener, levcromakalim (0.1-3
microM). In rabbit portal vein K+ currents induced by levcromakalim (10 microM)
or pinacidil (10 microM) were completely inhibited by tetraphenylphosphonium
(IC50 0.5 microM). The results show that tetraphenylphosphonium antagonizes the
KATP current induced by K+ channel openers in vascular smooth muscle possibly by
acting on the KATP channel itself.
PMID- 9650858
TI - Alpha1-adrenoreceptor stimulation causes vascular smooth muscle cell hypertrophy:
a possible role for isoprenoid intermediates.
AB - We investigated whether contraction-induced agonists such as alpha1-adrenoceptor
agonists are important regulators of smooth muscle cell hypertrophy by examining
the effects of one potent agonists, phenylephrine, on the hypertrophy. Under the
experimental conditions used, we found that phenylephrine was potent in inducing
alpha1-adrenoreceptor-dependent hypertrophy of vascular smooth muscle cells as
defined by increased incorporation of [14C]leucine in a dose-dependent fashion.
Further, we assessed the effect of lovastatin, an 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitor, on hypertrophy of cultured vascular
smooth muscle cells as defined by the increased incorporation of [14C]leucine
caused by phenylephrine. Lovastatin (5-15 microM) caused a significant dose
dependent reduction in [14C]leucine incorporation which was completely prevented
in the presence of exogenous mevalonate (100 microM). Exogenous low density
lipoprotein (100 microg/ml) and cholesterol (15 microg/ml) did not prevent
lovastatin inhibition of [14C]leucine incorporation. In contrast, the isoprenoid
farnesol largely prevented inhibition of [14C]leucine incorporation by the
lovastatin. We conclude that mevalonate metabolites are essential for
phenylephrine-induced smooth muscle cell hypertrophy, possibly through the
production of the isoprenoid farnesol.
PMID- 9650860
TI - An asparagine residue regulating conductance through P2X2 receptor/channels.
AB - Single channel currents were recorded from Xenopus oocytes expressing wild-type
and mutated P2X2 receptors. When 100 mM Na+ was used as the permeant cation,
unitary currents of about 80 pS were recorded from the oocyte expressing the wild
type channels. The single channel conductance was roughly halved when Asn333 was
replaced by Ile (N333I). A similar decrease in single channel currents was also
observed when 100 mM Li+ or Cs+ was used as the permeant cation. With two other
mutants, in which Asp315 was replaced by Val (D315V) or Tyr330 was replaced by
lie (T333I), single channel conductance was almost the same as that of the wild
type channels. The results suggest that Asn333, which is believed to be involved
in the channel pore, plays an essential role in ion transport through P2X2
receptor/channels.
PMID- 9650859
TI - Up-regulation of human alpha7 nicotinic receptors by chronic treatment with
activator and antagonist ligands.
AB - This study examined the binding and functional properties of human alpha7
neuronal nicotinic acetylcholine receptors stably expressed in human embryonic
kidney (HEK) 293 cells following chronic treatment with nicotinic receptor
ligands. Treatment of cells with (-)-nicotine (100 microM) for 120 h increased
the Bmax values of [125I]alpha-bungarotoxin binding 2.5-fold over untreated
cells. This effect was concentration-dependent (EC50) = 970 microM) and a 6-fold
upregulation was observed with the maximal concentration of (-)-nicotine tested.
Also, treatment of cells with ligands of varying intrinsic activities including
(+/-)-epibatidine, (2,4)-dimethoxybenzylidene anabaseine (GTS-21) and 1,1
dimethyl-4-phenyl piperazinium iodide (DMPP) also upregulated [125I]alpha
bungarotoxin binding. A concentration-dependent upregulation of binding sites was
also observed following treatment with the alpha7 nicotinic receptor antagonist,
methyllycaconitine (EC50 = 92 microM) with a maximal upregulation of about 7
fold. Functionally, the peak amplitude of the whole-cell currents recorded by
fast application of (-)-nicotine after chronic treatment of cells with
concentrations of (-)-nicotine (1000 microM) or methyllycaconitine (10 microM)
that elicited similar increases in binding levels (3.5-fold) resulted in
increases of 2-fold (505 +/- 21 pA) and 6-fold (1820 +/- 137 pA) respectively in
whole cell current amplitude compared to untreated cells (267 +/- 24 pA). These
studies clearly demonstrate that long-term exposure to both activator and
antagonist ligands can increase the density of alpha7 nicotinic receptors and can
differentially enhance nicotinic receptor function.
PMID- 9650861
TI - Immunochemical characterization of in vitro culture-derived antigens of Babesia
bovis and Babesia bigemina.
AB - Cross-reactivity between Babesia bovis and B. bigemina becomes a problem in
discrimination of the two infections in endemic areas where the two species
usually occur in association. With the aim of identifying candidate proteins for
use as specific diagnostic tools, culture-derived components of three
geographically different stocks of B. bovis (Lismore, Kwanyanga and Mexico) and
one of B. bigemina (Mexico) were analyzed by immunoprecipitation using acrylamide
gel electrophoresis. The approach taken was based on the analysis of 35S
methionine-labelled parasite antigens released into culture supernatant. A
variety of serum samples were tested, including a panel of calf sera
experimentally produced against the different stocks of Babesia, serum samples
from cattle naturally infected in the field in Brazil, and a panel of anti-B.
bovis monoclonal antibodies, previously characterized by the indirect fluorescent
antibody test, ELISA and Western immuno-blotting. Approximately 28 and 23 bands
(with molecular weights ranging from 200 to 14 kDa) were detected in total
protein profiles of B. bovis and B. bigemina culture supernatants, respectively,
whereas no bands were seen in the uninfected red blood cell culture supernatant
(negative control). The immunoprecipitation analysis showed antigenic diversity
amongst the stocks of B. bovis and resulted in identification of at least five B.
bovis specific antigens common to the three stocks (molecular weights of 80, 72,
58, 38 and 24 kDa) and four B. bigemina specific antigens (molecular weights of
240, 112, 50 and 29 kDa).
PMID- 9650862
TI - Seroprevalence of Babesia equi among horses in Israel using competitive
inhibition ELISA and IFA assays.
AB - Sera from 361 horses were tested by indirect immunofluorescence antibody test
(IFA) and by competitive inhibition ELISA (cELISA), to detect antibodies to
Babesia equi. The concordance between the assays was 95.7%. Application of a
cutoff based on a calculated percent inhibition of < 20% gave a total of 22
discrepant results, while only 8 sera negative by the cELISA were found positive
by the IFA when a cutoff of > 20% inhibition was used. Approximately one-third of
all the horses tested were found serologically positive to B. equi, with more
horses testing positive from northern Israel. Among horses raised with access to
pasture there was a significant difference in the percentage of seropositive
reactors (76.6% in the north and 20.1% in the central region), compared with
horses without access to pasture (14.3 and 10.3%, respectively). Nineteen percent
of stallions were found to be positive, which was significantly less than the
proportions of seropositive mares and geldings: 38 and 42%, respectively. No
significant association was found between the mean age of horses and
seroreactivity to B. equi.
PMID- 9650863
TI - Coccidiosis in goats in the Czech Republic.
AB - An observational study was conducted to determine coccidial infections in goats
of 13 farms in the Czech Republic. The prevalence of oocysts of Eimeria species
in kids (less than 3 months old), weaned but not served goats (from 3 months to 1
year), and adult goats (1 year or more) was determined. Nine Eimeria species were
identified in fecal samples by Sheather's sugar flotation technique. The overall
prevalence of Eimeria oocysts in fecal specimens was 92.2%. Eimeria arloingi was
the most common species with an overall prevalence of 84%, followed by E. hirci
(63%) and E. ninakohlyakimovae (56%). Other species present were E. christenseni
(55%), E. alijevi (36%), E. caprina (25%), E. aspheronica (12%), E. capriovina
(6%) and E. jolchijevi (2%). Two or more Eimeria species were detected in 88% of
the samples. The most prevalent species in kids was E. arloingi, while in weaned
but not served and adult goats E. ninakohlyakimovae was the most frequently
found. The number of oocysts excreted was generally lower in adult goats
(2567.3+/-12678 OPG), whereas higher number oocyst per gram of feces (OPG) were
found in kids (18565+/-24888 OPG). Clinical coccidiosis was detected in two
farms, and E. arloingi and E. ninakohlyakimovae were implicated as its cause.
Disease was observed in kids 2 to 4 weeks after weaning and watery feces with
clumps of mucus, and color changes from brown to yellow or dark tarry, weight
loss, and dehydration were the most conspicuous clinical signs. At necropsy,
macroscopic changes included mucosal hemorrhages and whitish nodular polyps in
the jejunum were found. Histopathological changes were characterized by local
hypertrophy and hyperplasia of intestinal villi, villus blunting and inflammatory
infiltration in the lamina propria. Numerous developmental stages of the
parasites were observed in enterocytes and lacteals of intestinal villi.
PMID- 9650864
TI - Improved detection of circulating antigen in cattle infected with Taenia saginata
metacestodes.
AB - In order to improve the sensitivity and the specificity of an existing IgM
monoclonal antibody-based ELISA (Brandt et al., 1992) for the detection of
circulating antigen in the sera of cattle infected with T. saginata metacestodes,
a modified sandwich ELISA was developed. Monoclonal antibodies (MAbs) of the IgG
isotype were produced against the excretory-secretory (ES)-products of T.
saginata metacestodes. Since it was shown that the affinity of these IgG MAbs for
ES antigen was higher than that of the IgM MAbs, the latter were replaced by two
IgG1 MAbs (158C11 and 60H8). Furthermore, heat treatment of the sera
significantly increased the OD-values of ES-spiked serum samples as compared to
nontreated samples. It also decreased the number of false positive reactions.
When the original IgM MAb-based ELISA was compared with the IgG MAb-based ELISA
using heat treated sera from animals harbouring more than 50 living metacestodes
of T. saginata, the sensitivity increased from 56% with the former to 92% with
the latter assay. Only a small percentage of animals carrying less than 50 cysts
were detected both with the ELISA using IgG or IgM MAbs. The specificity of the
IgM- and IgG MAb-based ELISAs was 93.4% and 98.7% respectively.
PMID- 9650865
TI - Comparative analysis of two methods used to show interspecific associations in
naturally acquired parasite nematode communities from the abomasum of ewes.
AB - The aim of our study was to compare a multivariate and a univariate method to
evaluate the associations between nematode species in natural infections. We used
a data set based on the 3-year study of the community of abomasal nematodes in
ewes of the middle-Atlas region of Morocco. Frequency data (percentage of each
species in the individual host community) were processed by principal component
analysis. Euclidean distances between species (D2) were calculated from
projections of principal component analysis on three axes and compared to a
bivariate estimate (1 - correlation coefficient R). Low distances were recorded
between morphs of the same species (Teladorsagia circumcincta and T. trifurcata,
for example), which indicates a positive association. Only two species,
Trichostrongylus axei and T. circumcincta, were negatively associated having D2
values much over 1. The distances D2, i.e., multivariate measure of association
intensity were similar in most cases to 1- R estimates, indicating probably the
absence of strong multispecies association. The D2 fitted a Motomura geometric
progression model indicating that associations were arranged in a continuum from
low to high values, but they did not depart much from what could be expected from
random associations for most species. The D2 interest is mostly to relate
associations with environmental variables, and comparing with 1 - R, to assess
the degree of interaction in the community.
PMID- 9650866
TI - Effects of preventive anthelmintic treatment on acquired resistance to
gastrointestinal nematodes in naturally infected cattle.
AB - The objective of this study was to investigate the influence of different types
of chemoprophylaxis in first season grazing calves on their resistance against a
natural reinfection with Ostertagia ostertagi and Cooperia oncophora in the
second grazing season. Thirty helminth-naive crossbred calves were randomly
divided in three groups of 10 animals. The animals of group B received an
ivermectin sustained release bolus on day 0. The calves of group D were treated
on days 0 and 56 with a subcutaneous injection of doramectin (0.2 mg kg(-1) BW).
Group C was the untreated control group ('immune' controls). Although exposure to
gastrointestinal nematodes in the first grazing season was only limited, the
chemoprophylactic treatments in groups B and D resulted in three distinctly
different infection levels (group C > group D > group B). At the start of the
second grazing season, six helminth-naive steers (group N, 'susceptible'
controls) were turned out together with the second season animals. After 3 weeks
of grazing, the 'susceptible' controls were slaughtered, together with four
animals from each other group. Parasitological and immunological parameters
indicated that resistance to reinfection with Ostertagia was reduced in the
chemoprophylactic treated animals, and was negatively related to the degree of
suppression of host-parasite contact in the first grazing season (group C > group
D > group B > group N). None of the groups had developed a complete resistance
against Cooperia yet. A negative relationship was observed between reduction of
first grazing season exposure, and weight gains early in the second grazing
season. The remaining animals stayed on pasture until the beginning of November.
At the end of the second grazing season, levels of acquired resistance against
Ostertagia infection were similar in all groups, and all animals had become
immune against Cooperia. No effect of first year chemoprophylaxis on total weight
gains could be demonstrated. Because of discrepancy between pasture larval counts
and tracer worm counts, it was not possible to draw firm conclusions on the
effect of chemoprophylaxis on pasture infestation levels in the second year.
PMID- 9650867
TI - Intestinal parasites in swine in the Nordic countries: prevalence and
geographical distribution.
AB - In Denmark (DK), Finland (FIN), Iceland (I), Norway (N), and Sweden (S), 516
swine herds were randomly selected in 1986-1988. Individual faecal analyses
(mean: 27.9 per herd) from eight age categories of swine showed that Ascaris
suum, Oesophagostomum spp., Isospora suis, and Eimeria spp. were common, while
Trichuris suis and Strongyloides ransomi-like eggs occurred sporadically. Large
fatteners and gilts were most frequently infected with A. suum with maximum
prevalences of 25-35% in DK, N and S, 13% in I and 5% in FIN. With the exception
of the remarkably low A. suum prevalence rates in FIN, no clear national
differences were observed. Oesophagostomum spp. were most prevalent in adult pigs
in the southern regions (21-43% in DK and southern S), less common in the
northern regions (4-17% adult pigs infected), and not recorded in I. I. suis was
common in piglets in DK, I, and S (20-32%), while < 1% and 5% were infected in N
and FIN, respectively. Eimeria spp. had the highest prevalences in adult pigs
(max. 9%) without clear geographical differences. I. suis and Eimeria spp. were
recorded for the first time in I, and I. suis for the first time in N.
PMID- 9650868
TI - The control of the free-living stages of Strongyloides papillosus by the
nematophagous fungus, Arthrobotrys oligospora.
AB - Two laboratory trials were conducted to determine the effect of the addition of
spores (conidia) of the nematophagous fungus, Arthrobotrys oligospora, on the
development of the ruminant parasite, Strongyloides papillosus, in cultures of
bovine faeces. Both studies showed that at a concentration of 2000 conidia/g
faeces virtually eliminated infective larvae (> 99% reduction), following 14 days
incubation under ideal conditions (25 degrees C and saturated humidity) for free
living development of this parasite species. In one trial, a high level of
control was also observed at a 10-fold decrease in conidia concentration (200
spores/g faeces). This work has demonstrated, in principle, that A. oligospora
could provide a practical biological control agent against S. papillosus
infecting intensively raised young ruminants in the humid tropics/subtropics.
PMID- 9650869
TI - Subgingival microbiota in healthy, well-maintained elder and periodontitis
subjects.
AB - This investigation compared the site prevalence of 40 subgingival species in 30
periodontally healthy (mean age 36+/-9 years), 35 elders with a well-maintained
periodontium (mean age 77+/-5) and 138 adult periodontitis subjects (mean age
46+/-11). Subgingival plaque samples were taken from the mesial aspect of each
tooth (up to 28 samples) in the 203 subjects at baseline. The presence and levels
of 40 subgingival taxa were determined in 5003 plaque samples using whole genomic
DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments including
dichotomous measures of gingival redness, bleeding on probing, plaque
accumulation and suppuration, as well as duplicate measures of pocket depth and
attachment level, were made at 6 sites per tooth. The % of sites colonized by
each species (prevalence) was computed for each subject. Differences in
prevalence and levels among groups were sought using the Kruskal-Wallis test.
Commonly detected species, such as Actinomyces naeslundii genospecies 2,
Streptococcus sanguis and Streptococcus oralis did not differ significantly among
subject groups. After adjusting for multiple comparisons, 4 species were
significantly elevated and at greater prevalence in the periodontitis group. Mean
% of sites (+/-SEM) colonized by Bacteroides forsythus was 10+/-3, 12+/-2 and
40+/-2 (p<0.001) for healthy, elder and periodontitis groups respectively. The
odds ratio was 14.4:1 that a subject had periodontitis when B. forsythus was
detected at > or = 5% of sampled sites. Mean prevalence for Porphyromonas
gingivalis in healthy, elder and periodontitis subjects was 4+/-2, 5+/-2 and 23+/
2 respectively (p<0.001); for Treponema denticola 12+/-4, 10+/-3 and 30+/-2
(p<0.001) and for Selenomonas noxia 6+/-2, 7+/-2 and 19+/-2 (p<0.01). Similar
differences among subject groups were observed when only sites with PD 0-4 mm
were analyzed. The data suggest an etiologic role for B. forsythus, P.
gingivalis, T. denticola and S. noxia in adult periodontitis.
PMID- 9650870
TI - The use of metronidazole and amoxicillin in the treatment of advanced periodontal
disease. A prospective, controlled clinical trial.
AB - The present clinical trial was performed to study the effect of systemic
administration of metronidazole and amoxicillin as an adjunct to mechanical
therapy in patients with advanced periodontal disease. 16 individuals, 10 female
and 6 male, aged 35-58 years, with advanced periodontal disease were recruited. A
baseline examination included assessment of clinical, radiographical,
microbiological and histopathological characteristics of periodontal disease. The
16 patients were randomly distributed into 2 different samples of 8 subjects
each. One sample of subjects received during the first 2 weeks of active
periodontal therapy, antibiotics administered via the systemic route
(metronidazole and amoxicillin). During the corresponding period, the 2nd sample
of subjects received a placebo drug (placebo sample). In each of the 16 patients,
2 quadrants (1 in the maxilla and 1 in the mandible) were exposed to non-surgical
subgingival scaling and root planing. The contralateral quadrants were left
without subgingival instrumentation. Thus, 4 different treatment groups were
formed; group 1: antibiotic therapy but no scaling, group 2: antibiotic therapy
plus scaling, group 3: placebo therapy but no scaling, group 4: placebo therapy
plus scaling. Re-examinations regarding the clinical parameters were performed,
samples of the subgingival microbiota harvested and 1 soft tissue biopsy from 1
scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the
completion of active therapy. The teeth included in groups 1 and 3 were following
the 12-month examination exposed to non-surgical periodontal therapy, and
subsequently exited from the study. Groups 2 and 4 were also re-examined 24
months after baseline. The findings demonstrated that in patients with advanced
periodontal disease, systemic administration of metronidazole plus amoxicillin
resulted in (i) an improvement of the periodontal conditions, (ii)
elimination/suppression of putative periodontal pathogens such as A.
actinomycetemcomitans, P. gingivalis, P. intermedia and (iii) reduction of the
size of the inflammatory lesion. The antibiotic regimen alone, however, was less
effective than mechanical therapy with respect to reduction of BoP - positive
sites, probing pocket depth reduction, probing attachment gain. The combined
mechanical and systemic antibiotic therapy (group 2) was more effective than
mechanical therapy alone in terms of improvement of clinical and microbiological
features of periodontal disease.
PMID- 9650871
TI - Effect of a triclosan/copolymer dentifrice on the incidence of periodontal
attachment loss in adolescents.
AB - The aim of this study was to assess the effectiveness of a dentifrice containing
0.3% triclosan, 2.0% copolymer and 0.243% sodium fluoride (Colgate Total) in the
prevention of periodontal attachment loss in adolescents. A 3-year, double-blind,
randomised, controlled, clinical trial was conducted on 641 adolescents,
initially aged 11-13 years. The participants were enrolled from schools in
economically deprived areas of Manchester, England, which had a high % of Asian
pupils originating from India, Pakistan and Bangladesh. After the baseline
examination, which included assessments of pocket depth, attachment loss and
subgingival calculus, the adolescents were randomly allocated to use either a
triclosan/copolymer or control dentifrice. The control was identical to the test
dentifrice with the exception that it did not contain triclosan/copolymer.
Participants were re-examined after 18 and 36 months. After 3 years, a total of
239 adolescents remained in the test and 241 in the control group. The prevalence
of attachment loss increased from 2% at baseline to 24% after 3 years. The mean
increment of attachment loss during the study was 0.025 mm per site in the
control group and 0.018 mm per site in the test group. A linear regression model
showed a statistically significant difference in attachment loss between the test
and control group, in adolescents with high mean pocket depths at baseline. No
adverse effects attributable to the test or control dentifrices were observed
during the study. This study has demonstrated that unsupervised use of a
triclosan/copolymer dentifrice can significantly reduce periodontal attachment
loss, particularly in adolescents with high mean pocket depths.
PMID- 9650872
TI - Association of crevicular fluid elastase-like activity with histologically
confirmed attachment loss in ligature-induced periodontitis in beagle dogs.
AB - Experimental periodontitis was induced using ligatures in 6 beagle dogs over 57
days. Levels of elastase like activity in healthy sites, gingivitis sites, and in
sites ligated for different time points were analyzed with respect to levels of
histologically confirmed attachment loss. Attachment loss increased with
increasing periods of ligation and reached a maximum of 0.15 mm at 57 days.
Maximum loss of histological attachment was found to coincide with the period of
maximum enzyme activity; during the first 7 days of ligature. Spearman
correlation analysis of enzyme activity with attachment loss yielded a
significant correlation (0.73, p=0.0396). The healthy and gingivitis sites were
found to have minimal levels of enzyme activity throughout. Thus, this
prospective study in beagle dogs found a relationship between histologically
confirmed attachment loss and increased levels of elastase like activity
indicating the probable usefulness of this parameter, either alone or in
conjunction with other markers, for disclosing active periodontitis.
PMID- 9650873
TI - The effects of an ultrasonic toothbrush on plaque accumulation and gingival
inflammation.
AB - The purpose of this study was to evaluate the effectiveness of an ultrasonic
toothbrush to reduce plaque and gingival inflammation when compared to a manual
toothbrush. 62 healthy adult patients with a plaque index of at least 2.0, a 50%
bleeding index and at least 16 natural teeth participated in this study. 31
patients were randomly assigned to the manual toothbrush group (group A) and 31
were assigned to an ultrasonic toothbrush group (group B). The Turesky et al.
plaque index (PI), Eastman bleeding index, and Loe & Silness gingival index (GI)
were performed at baseline, 15, and 30 days at the beginning of each appointment
(pre-brushing). Patients then brushed with their assigned toothbrush and a post
brushing plaque index was recorded. Kruskal-Wallis one-way analysis of variance
(ANOVA) was performed to determine between group differences on the parameters of
all clinical indices. Results of the pre-brushing plaque index in group B were
significantly lower at 15 and 30 days compared to group A. The post-brushing
plaque index demonstrated no statistically significant between or within group
differences. Both groups demonstrated significant within group reductions in GI
and BI from baseline to 15 days and from 15 to 30 days, however, no between group
differences were noted. The results of this study support the ability of an
ultrasonic toothbrush to significantly remove plaque and reduce inflammation as
well as a manual toothbrush over a 30 day period.
PMID- 9650874
TI - Differential clinical treatment outcome after systemic metronidazole and
amoxicillin in patients harboring Actinobacillus actinomycetemcomitans and/or
Porphyromonas gingivalis.
AB - 48 adult patients with untreated periodontitis harboring subgingival
Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis as assessed
by PCR were randomly assigned to receive full-mouth scaling alone (control) or
scaling with systemic metronidazole plus amoxicillin and supragingival irrigation
with chlorhexidine digluconate (test). In patients harboring A.
actinomycetemcomitans intraorally at baseline, the adjunctive antimicrobial
therapy resulted in a significantly higher incidence of probing attachment level
(PAL) gain of 2 mm or more compared to scaling alone over 12 months (p<0.05). In
addition, suppression of A. actinomycetemcomitans in subgingival plaque below
detectable levels was associated with an increased incidence of PAL gain. In
contrast, patients initially harboring P. gingivalis but not A.
actinomycetemcomitans in the oral cavity showed a significantly higher incidence
of PAL loss following adjunctive antimicrobial therapy compared to scaling alone
(p<0.05). When the presence of pathogens at baseline was disregarded in the
analysis, adjunctive antimicrobial therapy did not significantly enhance clinical
treatment outcome. The results indicated that adults with untreated periodontitis
harboring A. actinomycetemcomitans may benefit from the adjunctive antimicrobial
therapy for a minimum of 12 months, whereas, the regimen may adversely affect the
clinical treatment outcome of patients harboring P. gingivalis but not A.
actinomycetemcomitans.
PMID- 9650875
TI - Instrumentation of furcation with modified sonic scaler inserts: study on
manikins, part I.
AB - The purpose of this study was to determine the suitability of different scaling
instruments for the debridement of furcations. 12 upper and 12 lower replicated
molars with through-and-through furcations were instrumented 3x with 5 different
types of instruments: (i) hand instruments; (ii) hand instruments in conjunction
with diamond burrs; (iii) a conventional ultrasonic scaler insert; (iv) a
conventional sonic scaler insert; (v) a set of 2 modified diamond coated sonic
scaler inserts with different angulated shafts. The plastic replicas were fixed
in a manikin head without replicated soft tissues. Following debridement, weight
loss and % of instrumented furcation area were assessed. In the case of lower
molars, it made little difference whether they were treated with hand
instruments, hand instruments combined with diamond burrs, or diamond-coated
sonic scaler inserts. On upper molars, however, significantly more area was
instrumented with the diamond-coated inserts than with the other instruments.
Substance removal was greater with diamond-coated inserts than with the other
devices. In conclusion, an effective debridement of the furcation seems possible
only with an odontoplasty, in which a furcation is fitted to the instrument by
means of intensive instrumentation, thus leading to substance loss. To improve
results with these instruments, further research is necessary.
PMID- 9650876
TI - Hyper-reactive peripheral neutrophils in adult periodontitis: generation of
chemiluminescence and intracellular hydrogen peroxide after in vitro priming and
FcgammaR-stimulation.
AB - We have earlier reported a higher Fcgamma-receptor (FcgammaR)-mediated generation
of reactive oxygen species, measured as luminol-enhanced chemiluminescence (CL)
from peripheral neutrophils in adult periodontitis patients. The aims of this
study were to confirm our previous results and to elucidate the mechanism of this
phenomenon by measuring CL in parallel with the intracellular production of
hydrogen peroxide, after stimulation with opsonized bacteria. To determine
whether the higher CL was associated with altered responsiveness to priming, the
cells were preincubated with tumor necrosis factor alpha (TNFalpha) and
lipopolysaccharide (LPS). While CL was significantly higher in subjects with
periodontitis, there was no difference in hydrogen peroxide production between
the patients and the controls, indicating that the hyperreactivity is related to
the generation of other oxygen species than H2O2 and/or to processes in the outer
cell membrane. The responsiveness to priming with LPS on CL was slightly but not
significantly higher in the periodontitis group, suggesting that priming could be
of value for distinguishing subjects with periodontitis. When assaying
intracellular production of H2O2, TNFalpha and LPS had both a priming and an
activating effect. There were no significant differences between the two groups.
In conclusion, this study shows a higher FcgammaR-mediated CL of peripheral
neutrophils from adult patients with periodontitis, thus confirming our earlier
results. The hyperreactivity seems to be related to the outer cell membrane or to
oxygen species other than H2O2.
PMID- 9650877
TI - The effect of herbal extracts in an experimental mouthrinse on established plaque
and gingivitis.
AB - The purpose of the present study was to establish in vitro the inhibiting effect
of a herbal extract mixture on a selected number of micro-organisms and to test
in vivo the effect of a mouthwash containing 6.3 mg/ml herbal extract mixture on
plaque and gingivitis as compared to a minus active control mouthrinse. The
herbal extract was a mixture of: Juniperus communis (juniper), Urtica dioca
(nettle), Achillaea millefolium (yarrow); 1:1:1. In the study, in-vitro, the
effect of pure herbal extract mixture on acid production of Streptococcus mutans
was tested and the minimum inhibitory concentrations (MIC) of the following micro
organisms were tested: Streptococcus mutans, Streptococcus mitis, Actynomyces
viscosus, Actynomyces naeslundii, Actinobacillus actinomycetemcomitans,
Prevotella intermedia, Campylobacter rectus, Fusobacterium nucleatum, Veillonella
parvula. The MIC-values for A. viscosus and P. gingivalis were 100 mg/ml. The MIC
values for A. naeslundii and A. actinomycetemcomitans were considerably lower (10
mg/ml). S. mitis was the most susceptible of the tested organisms to the extract
with a MIC value of 1 mg/ml. S. mutans, C. rectus, V. parvula, and F. nucleatum
were not influenced by the extracts. No inhibitory effect of the 6.3 mg/ml herbal
extract mixture was observed on the acid production of S. mutans. For the study
in-vivo, 45 volunteers were selected on the basis of having moderate gingival
inflammation. As efficacy parameters the plaque index, modified gingival index
and angulated bleeding index were assessed. The subjects were randomly divided
among 3 experimental groups (2x test and 1 'minus active' control). The
participants were requested to rinse with 10 ml of mouthwash twice a day for a
period of three months. After 6 weeks and 3 months, the same clinical indices as
at baseline were recorded. The results show no difference between the two test
groups and the control group. In conclusion, the results of the present study
have shown that the mixture of the 3 herbal extracts, Juniperus communis, Urtica
dioca and Achillaea millefolium when used in a mouthrinse has no effect on plaque
growth and gingival health.
PMID- 9650878
TI - Human periodontal ligament fibroblast response to PDGF-BB and IGF-1 application
on tetracycline HCI conditioned root surfaces.
AB - The purpose of this study was to investigate the effect of 2 growth factors,
platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF
1), alone or in combination, on the adherence of human periodontal ligament
fibroblast (PDL) to tetracycline HCl (TTC) conditioned and nonconditioned
periodontally involved root surfaces. There were 80 root dentine chips from 80
patients, ranging from 35 to 70 years of age, each with one periodontally
involved tooth requiring extraction. A root dentine chip was obtained from the
subgingival surface opposite to the periodontal pocket of each extracted tooth.
The dentine chips were randomly distributed into one of 8 groups. In group 1, PDL
fibroblasts were cultured and allowed to attach on the dentine surface. In group
2, PDL fibroblasts were cultured on a PDGF-BB pre-treated dentine surface and in
group 3, they were cultured on a IGF-1 pre-treated dentine surface. In group 4,
PDL fibroblasts were cultured on a dentine surface pretreated with a combination
of PDGF-BB and IGF-1. In group 5, PDL fibroblasts were cultured and allowed to
attach on the TTC conditioned dentine surfaces. In groups 6 and 7, surface of
dentine chips were conditioned with TTC and then were treated with PDGF-BB or IGF
1 respectively, followed by placement of PDL fibroblast and cultured. In group 8,
dentine surfaces were conditioned with TTC and then pre-treated with a
combination of PDGF-BB and IGF-1 before the fibroblasts were cultured. After 24 h
of incubation, the media was removed and samples were fixed and processed for SEM
at magnifications of x34, x750, x2000. Photographing and evaluation of samples
was performed at x750 in which fibroblast adherence was measured by counting
cells within a standard test area. The results of the non-TTC conditioned root
surfaces demonstrated a significant increase in fibroblasts adherence in the PDGF
BB and combination PDGF-BB/IGF-I treatment groups (groups 2, 4) when compared to
the control (group 1) as well as the TTC control (group 5). The combination of
PDGF-BB/IGF-1 (group 4) did not significantly improve the adhesion of cells
compared to PDGF-BB alone (group 2), but did significantly improve adhesion when
compared to IGF-1 alone (group 3). There were no significant differences in cell
morphology between the growth factor groups (groups 2, 3, 4) and control (group
1). In general, the cells demonstrated a flat, stellate-shaped morphology. The
results of the TTC conditioned root surfaces, showed a statistically significant
increase of cellular adherence in the PDGF-BB group (group 6) when compared to
the TTC control (group 5), similar to the non-TTC group (group 2). However, the
morphology of the cells in groups 5, 6, 7, and 8 demonstrated generally a rounded
or oval shape with only an occasional cell exhibiting a flat form. In the
experimental system of this study, the inclusion of PDGF-BB on the surface of
dentine chips increased the number of adhering PDL cells, and the addition of TTC
conditioning had little effect except to change the morphology of adhering cells.
PMID- 9650879
TI - Relationship between the plaque removal efficacy of a manual toothbrush and
brushing force.
AB - This survey investigated the association between the efficacy of plaque removal
and toothbrushing forces during a normal brushing regime. The 94 subjects
participating in this study were requested not to brush 24 h prior to the
experiment. Panelists brushed for 1 min with a manual toothbrush. Before and
after brushing, plaque was assessed using the Turesky modification of the Quigley
& Hein plaque index. A second 1-min exercise of brushing was carried out to
assess the toothbrushing force. The mean plaque reduction was 39%, with
vestibular surfaces being cleaned most effective (69%) and the lingual surfaces
the least (21%). The mean brushing force was 330 g. No correlation was observed
between efficacy and brushing force (r=0.14, p=0.16). The relationship between
pre- and post-brushing plaque was stronger (r=0.68, p<0.001). Multiple regression
analysis entering squared values of force as an independent variable into the
equation, indicated that the relation between efficacy and force was not linear.
A curve could be fitted to the plot (p=0.0004), demonstrating that up to a
certain level of force, an increase of force is associated with an increase in
efficacy (r=0.33, p<0.01). Beyond this point, application of higher forces
resulted in reduced efficacy (r=-0.49, p=0.03). As was calculated in this
particular test this 'transition' level of force was 407.4 g. The absence of a
correlation between brushing force and plaque removal efficacy suggests that in a
'user model' brushing situation, other factors than brushing force are of major
influence on the amount of plaque removed.
PMID- 9650880
TI - Probe penetration in relation to the connective tissue attachment level:
influence of tine shape and probing force.
AB - Previous research has shown that probing force and probe tine shape influence the
clinically assessed probing depth. The purpose of the present study was to
investigate the effect of tine shape and probing force on probe penetration, in
relation to the microscopically assessed attachment level in untreated
periodontal disease. In 22 patients, scheduled for partial or full mouth tooth
extraction and no history of periodontal treatment, 135 teeth were selected. At
mesial and distal sites of the teeth reference marks were cut. Three probe tines,
mounted in a modified Florida Probe handpiece, were tested: a tapered, a parallel
and a ball-ended; tip-diameter 0.5 mm. The three tines were distributed at random
over the sites. At each site increasing probing forces of 0.10 N, 0.15 N, 0.20 N,
0.25 N were used. After extraction, the teeth were cleaned and stained for
connective tissue fiber attachment. The distance between the reference mark and
the attachment level was determined using a stereomicroscope. The results showed
that the parallel and ball-ended tine measured significantly beyond the
microscopically assessed attachment level at all force levels; with increasing
forces, the parallel tine measured 0.96 to 1.38 mm and the ball-ended tine 0.73
to 1.06 mm deeper. The tapered tine did not deviate significantly from the
microscopic values at the forces of 0.15, 0.20 and 0.25 N. It can be concluded
that for the optimal assessment of the attachment level in inflamed periodontal
conditions, a tapered probe with a tip diameter of 0.5 mm and exerting a probing
force of 0.25 N may be most suitable.
PMID- 9650881
TI - Gingival dimensions after root coverage with free connective tissue grafts.
AB - Traumatic injury in the presence of a thin and narrow zone of gingival tissue may
lead to gingival recession. Especially in class I and II recessions, root
coverage may be accomplished with connective tissue grafts. In order to prevent
recurrent recession, altering gingival dimensions width and thickness might be of
advantage. In the present study, dimensions of gingiva were followed for 1 year
after root coverage with connective tissue grafts. The study population consisted
of 18 patients with a total of 28 class I or II recessions. Gingival width and
depth of the recession were measured with a caliper, and thickness of the
marginal tissue with an ultrasonic device. Periodontal probing depth was
determined with a pressure-controlled electronic probe. Mean (+/-sd) recession
depth at baseline was 3.1+/-1.4 mm. After 12 months, coverage amounted to 74+/
30%. Width of gingiva rose from 2.1+/-1.0 mm to 3.2+/-1.4 mm, whereas thickness
was increased from 0.8+/-0.3 mm to 1.5+/-0.7 mm, on average. No significant
alteration of periodontal probing depth was observed but a mean gain of clinical
attachment of 1.7+/-1.1 mm was ascertained. In a multiple regression analysis,
recession depth and presence of the recession in the maxilla, but not tooth type
significantly influenced relative root coverage (R2=0.34, p<0.01). Attachment
gain after surgery depended on baseline attachment loss and was negatively
influenced by smoking. The present results point to the possibility of doubling
gingival thickness after root coverage with connective tissue grafts.
PMID- 9650882
TI - Increase in gingival inflammation under academic stress.
AB - Several correlational questionnaire studies have observed a positive relationship
between psychological stress and periodontal diseases. This paper analyses the
effects of academic stress on periodontal health in a prospective quasi
experimental design. 26 medical students participating in a major exam and the
same number of medical students not participating in any exam throughout the
study period volunteered for the study. Bleeding on probing was assessed 4 weeks
prior to the exam period (baseline) and at the last day of the exam. Severe
deterioration in gingival health from baseline to the last exam day were observed
more frequently in exam students than in controls (p=0.014). 6 exam students but
only 1 control person developed a severe gingivitis at at least one formerly
healthy tooth throughout the study period. These results further support the
hypothesis that psychological stress is a significant risk factor for periodontal
inflammation. Future studies should examine factors mediating this relationship.
PMID- 9650883
TI - On the discussion concerning microbiological culture and DNA probes in the
detection of periodontopathogenic bacteria.
PMID- 9650884
TI - Direct observation of t-butyl alcohol frozen and sublimated samples using low
vacuum scanning electron microscopy.
AB - Frozen biological specimens in t-butyl alcohol were examined under a low-vacuum
environment in a "wet SEM" or "variable pressure SEM (scanning electron
microscope)" equipped with a cooling stage and highly sensitive backscattered
detector of the YAG type. After fixation with glutaraldehyde and osmium
tetroxide, rat tissue blocks (tracheae and kidneys), and cultured human carcinoma
cells were dehydrated with a graded series of t-butyl alcohol. The specimens were
directly frozen on the cooling stage at -10 degrees C, evacuated to 20 Pa in the
specimen chamber, and observed by detecting backscattered electrons at
accelerating voltages of 5-6 kV. The images became clearer 20 min after the
vacuum reached 20 Pa and revealed had good quality by 30 min, probably because t
butyl alcohol was sublimated during the time. The cilia of tracheal ciliated
cells, end-feet of the podocytes of the renal glomerulus, and processes of
cultured cells were clearly observed without any serious preparation artifacts.
Since the low-vacuum SEM of t-butyl alcohol frozen samples is both simple and
provides high imaging quality, it is expected to be useful in a variety of
biological fields such as the rapid pathological diagnosis.
PMID- 9650885
TI - Immunocytochemical localization of chromogranin A and secretogranin II in female
rat gonadotropes.
AB - Ultrastructures of pituitary gonadotropes are known to show a prominent sex
related difference: typical male rat gonadotropes contain both large- and small
sized granules, whereas typical female rat gonadotropes appear to exhibit
uniformly small-sized granules. Our preceding studies have demonstrated that two
representative granins, chromogranin A (CgA) and secretogranin II (SgII), are
separately localized to each type of granule in male rat gonadotropes. To clarify
whether or not there is a certain relationship between granin proteins and
characteristic features of secretory granules in female rat gonadotropes, we
examined the expression levels and immunocytochemical localizations of CgA and
SgII in the cells. Northern blot and immunoblot analyses demonstrated that both
CgA and SgII were synthesized and stored in the female pituitary, although the
amount of CgA was much lower in the female than that in the male pituitary.
Immunocytochemical observations clarified that gonadotropes in the female
pituitary possessed intermediate secretory granules containing both CgA and SgII,
in addition to solely CgA-positive and SgII-positive ones. However, secretory
granules containing CgA in the female gonadotropes were much smaller in size and
appeared less frequently than those in the male cells, whereas no sexual
difference was discerned in SgII-positive granules. Moreover, the size and
appearance of CgA-positive secretory granules varied depending on stages of the
estrous cycle. These findings suggest that the size and appearance of secretory
granules containing CgA are closely associated with the expression and storage
levels of CgA in the pituitary.
PMID- 9650886
TI - Evidence for polymorphism of Merkel cells in the adult human oral mucosa.
AB - We recently reported that Merkel cells in the normal palatine mucosa of adult
rodents are highly polymorphic. In order to ascertain whether or not this
polymorphism is also evident in the human oral mucosa, palatine mucosae from
cadavers without oral diseases and perilesional palatine mucosae of patients with
pleomorphic adenoma were examined by immunohistochemistry using an antibody
against cytokeratin 20. Findings showed that Merkel cells in the human normal
palatine mucosa were polymorphic, and a number of irregular-shaped Merkel cells
(dendritic Merkel cells) with apparent cytoplasmic projections were present among
typical oval to round Merkel cells. The mucosa usually contained a small number
of oval to round Merkel cells residing in ectopic places such as prickle and
granular cell layers. On the other hand, the slightly inflamed perilesional
palatine mucosa contained an increased incidence of dendritic Merkel cells.
Ectopic Merkel cells were rare in the perilesional palatine mucosa.
Characteristics of dendritic Merkel cells were examined using specimens from
perilesional palatine mucosae by means of immunohistochemistry and electron
microscopy. It was shown that every dendritic Merkel cell and most roundish
Merkel cells in the perilesional mucosa lacked innervation. Electron microscopy
suggested that dendritic Merkel cells release secretory granules from the tip of
the cytoplasmic process and the basal cytoplasm towards the lamina propria
mucosae, in a manner resembling the case of similar cells in rodents.
PMID- 9650887
TI - Molecular weight-dependent effects of hyaluronate on the arthritic synovium.
AB - Intra-articular injection of hyaluronate (HA) is widely used in the treatment of
arthropathies. However, the mechanism of the effects of HA preparations on the
arthritic synovium and the relationship between their effects and molecular
weights (MW) remains unknown. The objectives of this study were to compare the
effects of two hyaluronate preparations, HA84 (MW: 84 X 10(4)) and HA230 (MW: 230
X 10(4)), on the synovium of an arthritis model and to examine the mechanism of
the effects of HA. The HA preparations were intra-articularly injected in a model
of canine arthritis induced by anterior cruciate ligament transection for a total
trial of 5 weeks. To define the accessibility of HA preparations to the synovial
lining layers, fluorescein-labeled HA84 or HA230 was injected at the last
administration. Pathological changes analyzed included increases in volumes and
prostaglandin E2 concentrations in synovial fluids, thickening of the synovial
lining layers, vacuolar alterations in the lining cells, and stainability of HA
in the synovium. Expression levels of Heat shock protein 72 (Hsp72) were
immunohistochemically detected in the tissues to investigate the ability of the
cells to survive the degeneration. The pathological changes described above were
more significantly suppressed in the HA84-treated than in the HA230-treated
groups. In most cases of the HA84-treated group (five cases out of six),
fluorescein particles were intensely distributed in the synovial lining layers,
but only two cases in the HA230-treated group showed a weak distribution of
fluorescein particles in the layers, indicating a certain difference in the
accessibility of HA preparations to the lining cells between the two HA
molecules. Moreover, the immunoreactivity for Hsp72 in the lining cells as more
intense in the HA84-treated than in the HA230-treated groups. The difference in
the accessibility of HA molecules corresponded well with that in the inducibility
of Hsp72 in the lining cells. These results suggest that the up-regulation of
Hsp72 may offer a new concept concerning mechanism of the effects of HA
preparations on the arthritic synovium.
PMID- 9650888
TI - Development of diaphragmatic lymphatics: the process of their direct connection
to the peritoneal cavity.
AB - The development of the lymphatic system in the rat diaphragm was studied from
embryonic day 16 to 25 weeks after birth by histochemistry for 5'-nucleotidase,
scanning electron microscopy of KOH-treated or intact tissues, and transmission
electron microscopy of thin sections. On embryonic day 16, distinct lymphatics
were noted in the subpleural space of the diaphragm periphery. The endothelial
cells at this stage contained an abundance of rough endoplasmic reticulum, a
developed Golgi apparatus and mitochondria, and fewer pinocytotic vesicles than
those in adults. The subpleural lymphatics subsequently increased and formed a
polygonal network. They possessed many valves, and by postnatal week 6, some
thick collecting lymphatics became endowed with smooth muscle cells. On embryonic
day 19, some lymphatics appeared in the subperitoneal space. They extended
centripetally and had many lateral projections that subsequently became elongated
and connected with those from adjacent lymphatics, thus forming a lattice-like
network. During the early postnatal days, the subperitoneal lymphatics projected
many bulges that subsequently became elongated, and came into contact with the
pores among the mesothelial cells, thus forming lymphatic stomata connecting the
lymphatic lacunae to the peritoneal cavity. The lymphatic stomata increased until
postnatal week 10. The results show that lymphatics appear as early as embryonic
day 16 in the subpleural space of the diaphragm periphery, and develop with age
by sprouting to form networks in both the subpleural and the subperitoneal
spaces, and that the direct connection of the lymphatic lacunae to the peritoneal
cavity is formed after birth.
PMID- 9650889
TI - Immunohistochemical identification of type B intercalated cells in the rat kidney
by a monoclonal antibody.
AB - We recently produced monoclonal antibodies using macrophagic cells derived from
cultured rat glomeruli as the antigen. One of the antibodies, named OS-3, was
found to detect a cell population scattered in collecting ducts of the rat kidney
as well as macrophages in various tissues. The present study deals with the
cellular and subcellular localization of immunoreactivities with OS-3 in the
kidney and other organs of rats. Double immunostaining using OS-3 and an anti
serum against either calbindin or epidermal cytokeratin showed that OS-3
immunoreactive cells exist exclusively in both the connecting segment and
cortical collecting duct, and differ from calbindin- or cytokeratin-positive
epithelial cells. Ultrastructurally, OS-3-immunoreactive cells appeared spherical
in shape with few cytoplasmic microprojections on the narrow apical surface.
Their relatively dark cytoplasm contained numerous mitochondria and a developed
tubulo-vesicular system. The intense immunoreactivity was selectively localized
in the basolateral membrane exhibiting shallow but complicated infoldings.
Distribution and ultrastructural properties of the OS-3-immunoreactive cells
showed that they were type B intercalated cells, which are engaged in the
regulation of the acid-base balance mainly by secreting HCO3-. Another positive
staining with OS-3 was found in the macula densa and some epithelial cells of
Bowman's capsule, the former monitoring Cl- concentrations in the urine.
Immunoblotting of extracts from the rat kidney demonstrated a protein band
immunoreactive to OS-3 at a molecular weight of 43 kDa. Aside from the kidney, a
specific and intense immunoreactivity with OS-3 was also found in the epithelial
cells of the pancreatic excretory duct and in the secretory cells of the
salivary, pyloric and duodenal glands, all of which are HCO3- -secreting cells.
These immunohistochemical findings imply that OS-3 is useful for the detection of
type B intercalated cells and recognizes a functional molecule involved in the
production/secretion of HCO3- or transport of Cl-.
PMID- 9650890
TI - Novel S100 proteins in human esophageal epithelial cells: CAAF1 expression is
associated with cell growth arrest.
AB - CAAF1 and CAAF2, newly identified calcium-binding proteins from bovine amniotic
fluid, have been revealed to be members of the S100 protein family preferentially
produced by fetal squamous epithelial cells, including epidermal keratinocytes.
Having previously cloned the cDNA of human CAAF1 protein from the esophageal
epithelium, we report here on the characteristic expression pattern of CAAF1 and
related S100 proteins in human esophageal epithelial cells. Normal cells of the
human esophageal epithelium expressed CAAF1, and also expressed the homologous
novel S100 proteins including CAAF2, MRP8, and MRP14, but not S100alpha. An
immunohistochemical study with specific monoclonal antibodies against CAAF1
proteins demonstrated that CAAF1 proteins were produced by the esophageal
epithelial cells in the process of cell differentiation. The immature
proliferating cells in the epithelium did not produce CAAF1 proteins, but the
differentiated cells expressed CAAF1, which overlay the immature cells and were
stratifying in the epithelium. These CAA 1-producing cells did not show any
proliferating activities. Esophageal carcinoma cells did not express CAAF1,
except for the keratinized cells with no proliferating activity. In addition, the
forced expression of CAAF1 proteins in the carcinoma cells resulted in a marked
decrease in DNA synthesis. These findings indicate that human esophageal
epithelial cells express the multiple genes of S100 proteins including CAAF
proteins, and that CAAF1 is closely associated with the terminal differentiation
of these cells. CAAF1 expression also might play some role in cell growth.
PMID- 9650891
TI - Embryonic development of the inner ear and otolith of the rainbow trout
Oncorhynchus mykiss.
AB - The embryonic development of the inner ear, especially the sensory epithelia and
otoliths in the rainbow trout Oncorhynchus mykiss, was studied by light and
electron microscopy. Light microscopically, the auditory vesicle, saccular
otolith and statoacoustic ganglion were first observed by 12 days after
fertilization, while the utricular otolith appeared at 15 days after
fertilization. Both the saccular and utricular maculae were more developed at 22
days after fertilization, and well developed by 27 days. The crista ampullaris of
the horizontal canal was also developed at 27 days after fertilization, while the
other cristae were not yet distinguished. Electron microscopically, vesicular
structures and short microvilli were found on the sensory epithelia of the
maculae by 15 days after fertilization. At 22 days after fertilization, the
saccular otolith possessed 7 incremental layers, and developing cilia,
microvilli, and aggregates of secretory materials also appeared on the apical
surface of the sensory epithelia. At 27 days after fertilization, the apical
surface of each hair cell was covered with a hair bundle consisting of a single
kinocilium and a bundle of stereocilia. These findings are discussed with special
regard to the environmental factors on early development in fishes.
PMID- 9650892
TI - MRI findings of multiple malignant gliomas: differentiation from multiple
metastatic brain tumors.
AB - Multiple malignant gliomas are relatively uncommon, but are sometimes difficult
to differentiate from multiple metastatic brain tumors. We analyzed the MR
findings of four cases of multiple gliomas, comparing them with 12 cases of
multiple metastatic brain tumors. All tumors were pathologically proven by
surgical operation or autopsy. Gliomas were located in the deep white matter of
the cerebrum, with none found in the posterior fossa. Tumors were relatively
large, and irregular, thick, ring-like enhancement was noted after the
administration of Gd-DTPA. Intratumoral hemorrhage was noted in only one case.
High signal intensity on T2WI around the tumor suggested that edema was greater
and more extensive than in metastatic tumors and was seen even in the corpus
callosum. One autopsied case that showed this high intensity presented not only
edema but also tumor infiltration. Metastatic tumors were located mainly in the
corticomedullary junction of the brain. They were relatively small, and eight of
12 tumors showed, nodular or smooth ring-like enhancement. Intratumoral
hemorrhage was noted in four cases. Edema was noted mainly around the tumor. We
conclude that differential diagnosis between gliomas and metastases is possible
to some extent by MRI.
PMID- 9650893
TI - Screening helical CT for mass screening of lung cancer: application of low-dose
and single-breath-hold scanning.
AB - PURPOSE: To investigate the usefulness of helical CT with low-dose and single
breath-hold scanning for lung cancer screening. MATERIALS AND METHODS: Twenty
four helical CT scans of the lung were performed using various parameters in 10
healthy volunteers. The effects of tube current and pitch were evaluated by
assessment of image quality and detection of simulated nodules. Screening helical
CT was performed at 120 kVp, 50 mA, 1 sec/rotation, 10 mm collimation, and a
pitch of 2.0 in 110 patients. The ability of this method to detect nodules and
masses, focal parenchymal opacities, and diffuse fibrotic changes was evaluated
using conventional CT as the gold standard. RESULTS: A reduction in tube current
to 50 mA did not significantly change the assessment of image quality or
detection of simulated nodules. Although these factors were degraded by
increasing the pitch, there was no significant difference between 1.5 and 2.0.
Screening helical CT permitted the entire lung to be scanned with ease during a
single-breath-hold in all patients. This method detected 177 of 196 nodules and
masses (87 of 91 lesions greater than 5 mm in diameter), 54 of 57 focal
parenchymal opacities, and 15 of 15 cases with fibrotic changes. CONCLUSION:
Screening helical CT with low-dose and single-breath-hold scanning shows promise
for lung cancer screening.
PMID- 9650894
TI - Evaluation of reconstructed hepatic veins with breath-hold 2D time-of-flight MR
venography.
AB - PURPOSE: The purpose of this study was to assess the ability of magnetic
resonance (MR) venography to evaluate the patency of reconstructed hepatic veins
after surgery. PATIENTS AND METHODS: Five normal volunteers with normal hepatic
veins and eight patients who underwent reconstruction of the hepatic veins after
resection of hepatic tumors were included. All subjects underwent breath-hold two
dimensional (2D) time-of-flight MR venography using a fast low angle shot (FLASH)
technique with a 1.5 Tesla magnet. The initial imaging plane was coronal, and
sagittal and/or transverse planes were added when necessary. Data were
postprocessed with a maximum intensity projection (MIP) algorithm. In six
patients, the MR findings were verified by iodinated hepatic venography. RESULTS:
The confidence level increased when patency was evaluated using a combination of
MIP and source images or other imaging planes compared with the use of MIP images
alone (3.0 to 3.6, p < 0.05). A signal drop near the orifice at the inferior vena
cava was observed in three normal patients. The severity of stenosis was
overestimated by MR venography in five patients. Obstruction was correctly
suggested in one patient. CONCLUSION: Although 2D time-of-flight MR venography
overestimated stenosis of the hepatic vein at the site of connection, it might
provide information on the patency of reconstructed hepatic veins especially when
more than one orthogonal plane is used and both MIP and source images are
evaluated.
PMID- 9650895
TI - CT angiography with helical CT in the assessment of acute stage of subarachnoid
hemorrhage.
AB - PURPOSE: We evaluated the usefulness of helical CT in the preoperative assessment
of ruptured cerebral aneurysms during the acute stage of subarachnoid hemorrhage
(SAH). METHODS: Nine patients with 13 aneurysms were included in this study.
Helical CT scanning was performed before preoperative angiography. The section
thickness and the table-movement speed were 1-2 mm/sec. Helical CT scanning was
started 20 sec after the start of injection of 100 ml of contrast agent at a rate
of 3 ml/sec. RESULTS: The average CT value of SAH was 51.9 Hounsfield units (HU)
and that of the aneurysm was 191.7 HU. Nine of 13 aneurysms greater than 3.0 mm
in diameter were identified by three-dimensional CT angiography (3DCTA). In seven
cases, the information provided by 3DCTA images, maximum intensity projection
images, and multiplanar images, was very useful in surgical planning, providing
information concerning the configuration of the neck and relationships between
the aneurysm and brain parenchyma. Four aneurysms in two cases were not depicted
by 3DCTA because they were located outside the imaging volume. This problem was
overcome by changing the imaging volume according to the extent of origin of SAH.
CONCLUSION: We conclude that helical CT in patients with SAH is useful for
surgical planning, providing valuable information that cannot be obtained by
conventional angiography.
PMID- 9650896
TI - Imaging techniques for measuring adipose-tissue distribution in the abdomen: a
comparison between computed tomography and 1.5-tesla magnetic resonance spin-echo
imaging.
AB - Eight subjects were examined both by abdominal X-ray computed transverse axial
tomography (CT) and magnetic resonance imaging (MRI) (SE) (TR/TE, 200 ms/15 ms);
another eight volunteers were subjected to three MRI scans to test the
reliability of repeated measures. Correlations between fat area measures obtained
by CT and by MRI for subcutaneous fat, total fat, and visceral vs. subcutaneous
fat ratio were highly significant (r = 0.93, 0.91, and 0.94, respectively; p <
0.01), and the standard errors of estimation were 9.99, 23.87, and 0.0047. The
average errors of the method for different fat areas were 2.20 cm2 (intra
examination variance) and 3.75 cm2 (inter-examination variance) for visceral and
0.82 cm2 (intra-examination variance) and 1.29 cm2 (inter-examination variance)
for subcutaneous fat areas, respectively. These results suggest that SE MRI is a
practical approach to evaluate body fat distribution without the exposure to
radiation. The reproducibility of SE MRI for the determination of fat areas is
high; variation is small and acceptable. However, it is difficult to determine
which estimate of fat area should be accepted when there is a discrepancy between
MRI and CT measures.
PMID- 9650897
TI - Treatment in patients with glioblastoma multiforme and poor performance status:
is it worthwhile?
AB - It has not been ascertained that treatment of glioblastoma multiforme of the
brain (GMB) favorably alters the prognosis in patients with poor pretreatment
performance status (PPS). We report on 52 patients with GMB and PPS. The mean
survival of 43 treated persons was 19 +/- 12 months (95% confidence interval) and
of nine untreated individuals, 2 +/- 1 months (p > 0.50); the corresponding
survival rates at 1 year were 39 +/- 16% and 0% (p > 0.05) and at 2 years, 15 +/-
12% and 0% (p > 0.40). We recommend active treatment of patients with GMB even
when they present with poor functional status.
PMID- 9650898
TI - Prognostic value of anti-Epstein-Barr virus antibodies in nasopharyngeal
carcinoma (NPC).
AB - INTRODUCTION: Epstein-Barr virus (EBV) is a ubiquitous human herpes virus with
worldwide infection. It is associated with Burkitt's lymphoma in Africa and
nasopharyngeal cancer (NPC) in Asian countries. EBV-coded DNA was found to be
present in epithelial elements of NPC, and is usually associated with non
keratinizing (WHO type II) or undifferentiated carcinoma (WHO type III).
Transcriptional analyses of EBV genome expression in NPC demonstrate an activated
viral state in some of these tumors, leading to elevated levels of serum anti
viral capsid antigen (VCA) antibody in NPC patients. METHODS: Eighty patients
with histological diagnoses of NPC according to the 1978 WHO classification were
referred to the Department of Radiation Oncology at Chang-Hua Christian Hospital
for curative radiotherapy from 1985 to 1995. The patients were staged according
to the AJCC staging system. A mean dose of 7,020 cGy in 39 fractions was
delivered to the primary tumor using a telecobalt-60 unit or 6-10 MV X-ray linear
accelerator. Pre- and postradiotherapy serum levels of anti-EBV/VCA IgG and IgA
were determined for all patients using the indirect immunoperoxidase assay (IPA).
Multivariate analysis was done to determine which factors affected the patients'
treatment outcome and survival. RESULTS: Five patients were excluded from this
study due to incomplete radiotherapy, leaving 75 patients eligible for analysis.
Overall local control was 77.3%, with a mean disease-free interval of 19.7
months. Factors affecting local control included radiation dose and pretreatment
anti-EBV/VCA IgG titer. The overall 5-year actuarial survival for the 75 patients
was 75%, with a median survival of 129.5 months. The 5-year actuarial survival
rates for stage I + II, III, and IV patients were 90%, 40%, and 45%,
respectively. Prognostic factors for survival included tumor histological type
and pretreatment anti-EBV/VCA IgA titer, while prognostic factors for local
control included total radiation dose received and pretreatment anti-EBV/VCA IgG
titer. CONCLUSION: We found that there was a significant difference in the
geometric mean titer of anti-EBV/VCA IgA antibodies before and after
radiotherapy. Prognostic factors affecting NPC patients' actuarial survival
included tumor histology and pretreatment IgA titer, while prognostic factors for
local control of NPC included total radiation dose received and pretreatment IgG
titer.
PMID- 9650899
TI - Pitfalls of CT diagnosis of aortic dissection: nonvisualized intimal flap in the
ascending aorta or aortic arch.
AB - We describe our experience with initial CT scans that failed to demonstrate an
intimal flap in the ascending aorta or aortic arch that was subsequently
identified on echocardiography, angiography, or MR imaging in four patients. This
problem was presumably caused by the flailing motion of a thin intimal flap and
localized small dissection in the ascending aorta, or transverse intimal flap
within the aortic arch. Radiologists should be aware of this pitfall in CT
diagnostic imaging.
PMID- 9650900
TI - Appendiceal abscess mimicking infected urachal cyst in a child with intestinal
malrotation.
AB - An appendiceal abscess with intestinal malrotation can occur anywhere in the
abdomen, not only in the right lower quadrant. We report a case presenting a
midline mass of the lower abdomen whose computed tomography (CT) and
ultrasonography (US) findings mimicked a urachal abscess. A retrospective review
of CT findings led to the correct diagnosis by showing malposition of the
ascending colon.
PMID- 9650901
TI - A case of chest wall Castleman's disease.
AB - We describe the findings of a rare case of right anterior chest wall Castleman' s
disease of the hyaline vascular type. It manifested as a solitary mass, 7.5 x 4.5
x 3.0 cm in size, with incomplete border and extrapleural signs on chest
roentgenograms. The mass was hypoechoic with numerous tiny bright spots on US; it
enhanced homogeneously on CT, had a homogeneously high intensity on both T1- and
T2-weighted MR images, and showed rich vascularity with homogeneous capillary
blush on internal thoracic arteriogram.
PMID- 9650902
TI - Case report: MR findings of Guillain-Barre syndrome.
AB - Guillain-Barre syndrome (GBS) is characterized as an acute, symmetrically
progressive, inflammatory demyelinating polyneuropathy. We report a case of GBS
in which gadolinium-enhanced magnetic resonance (MR) imaging showed marked
enhancement of nerve roots of the conus medullaris and cauda equina. On enhanced
MR imaging, the spinal cord and nerve roots in the thecal sac generally do not
take up much gadolinium because of the blood-nerve barrier or blood-brain
barrier. Therefore, in our case, marked enhancement of nerve roots indicates a
breakdown of the blood-nerve barrier. It is thought to correlate with the
inflammatory infiltration of GBS.
PMID- 9650903
TI - Primary central nervous system lymphoma presenting as diffuse cerebral
infiltration.
AB - We report a case of primary central nervous system lymphoma presenting as diffuse
cerebral infiltration. On T2-weighted spin echo MR imaging using a 1.0 Tesla
unit, high signal intensity lesions were presented mainly in the bilateral
pyramidal tracts and also diffusely extended to white matter with brain swelling.
No enhancing lesion was demonstrated after the intravenous injection of
Gadolinium-DTPA, during the course of her disease. Radiological diagnosis of
gliomatosis cerebri was made because of the characteristic MR appearance.
Stereotactic biopsy was performed, and diffusely scattered lymphocytes, probably
neoplastic, in the cerebral white matter were demonstrated histopathologically.
Oral corticosteroids, radiation therapy, and chemotherapy were applied soon after
her admission. The patient's condition improved dramatically. MR imaging using a
1.5 Tesla unit after the treatments showed marked regression and reduction of
high intensity lesions on T2-weighted images and improvement of brain swelling.
It should be emphasized that brain biopsy is important method for correct
diagnosis in case of diffuse non-enhancing brain lesions like our case.
PMID- 9650904
TI - Endovascular management of an aneurysm arising from posterior inferior cerebellar
artery originated at the level of C2.
AB - A 22-year-old man was admitted with a spontaneous subarachnoid hemorrhage. Right
vertebral angiography demonstrated an aneurysm arising from a distal segment of
an anomalous posterior inferior cerebellar artery (PICA) at the level of C 1. The
PICA originated from the third segment of the vertebral artery at the level of
C2. The lesion was treated with endovascular techniques, and the patient suffered
no residual neurological deficits.
PMID- 9650905
TI - Percutaneous fenestration of type B aortic dissection for decompression of false
lumen pressure: case report.
AB - We describe our experience with percutaneous treatment by transfemoral balloon
fenestration of the abdominal aorta in a patient with type B aortic dissection.
Percutaneous fenestration was effective in reducing the pressure in the false
lumen and equalizing the pressure between the two lumens. The patient was doing
well at three-year follow-up.
PMID- 9650906
TI - Effect of the distribution of radioactive sources on deadtime loss in a single
crystal gamma camera.
AB - Quantitative studies with a single-crystal gamma camera often require correction
for deadtime count loss. We evaluated the deadtime characteristics of a gamma
camera using point sources. Point sources with various radioactivities were
measured, and the relation between radioactivity and count rate was assessed. Two
sources with different activities were imaged apart or adjacent to each other,
and the effect of the geometrical distribution on counting efficiency was
investigated. Count loss was increased at a high radioactivity level, and was
well corrected using a nonparalyzable model and a deadtime of 4.99 microsec. It
was not affected by the distance between the two sources, and occurred equally
for the two sources imaged together. The count loss in imaging two sources was
successfully corrected by multiplying the obtained image by a correction factor
based on the count rate in the whole field-of-view. These results support the
reliability of the analytic technique for deadtime correction.
PMID- 9650907
TI - Reirradiation therapy for brain metastases from small cell lung cancer.
AB - Three patients with recurrence of brain metastases from small cell lung cancer
were treated with whole brain reirradiation therapy. A total dose of 20 Gy was
administered to two patients with hyperfractionation (20 fractions) and to one
with conventional fractionation (10 fractions). Two cases achieved PR and the
other NC. Survival after reirradiation was four months for all patients. Two
patients died of progressive brain metastases and one patient of liver
metastases. No radiation injury was observed during follow-up. Whole brain
reirradiation at a dose of 20 Gy in 10 or 20 fractions was therefore considered
useful and safe for brain recurrence of small cell lung cancer.
PMID- 9650908
TI - Chemoembolization of maxillary tumors via the superficial temporal artery using a
coaxial catheter system.
AB - A preliminary experience of embolization of maxillary tumors via the superficial
temporal artery using a coaxial catheter system is presented. Five patients with
maxillary carcinoma were slated to undergo embolization before radical surgery.
Embolization with carboplatine microcapsules was performed via the superficial
temporal artery using a coaxial catheter system. Carboplatine microcapsules
consisted of 60% (W/W) carboplatine core and 40% (W/W) ethylcellulose shell.
Embolization was performed twice in three patients, three times in one patient,
and once in one patient. The interval between embolizations was from one to three
weeks. The total dose of carboplatine microcapsules given ranged from 100 to 230
mg. Responses to the treatment were determined by measurements of tumor reduction
and increase in low attenuation areas of the tumor on postcontrast CT. Tumor
reduction over 48% was achieved in four of five tumors. All the tumors showed an
increased area of low attenuation in the tumor on the postcontrast CT after
embolization. No significant complications occurred. This method makes it easy to
superselectively repeat embolization.
PMID- 9650909
TI - Relationship among age, prostate-specific antigen, and prostate volume in men
with lower urinary tract symptoms (LUTS) and in different groups of men with and
without benign and malignant prostate diseases.
AB - BACKGROUND: In order to enhance prostate-specific antigen (PSA) as a predictor of
prostate cancer, it is necessary to understand the characteristics of this tumor
marker in a population of men without evidence of prostate cancer but who are at
risk for developing the condition. METHODS: In an age-stratified population of
328 men with lower urinary tract symptoms (LUTS), we analyzed the distribution of
PSA levels as a function of age and prostate volume, and we analyzed the
percentage of age-related variance in PSA that can be explained by the age
related variance in prostate volume. RESULTS: Classifying the 328 cases with LUTS
according to four age groups, a correlation was found between PSA and prostate
volume, becoming stronger from the younger (correlation coefficient, -0.1265) to
the older group (correlation coefficient, 0.6044). Serum PSA variance per
milliliter of prostate volume also increased from the younger (not significant, P
> 0.1) to the older age decades (7.3% in men age 70 years or over). Moreover, the
results of the regression analysis suggest that 10% of the variance in PSA with
age can be accounted for by prostate volume in men under age 50 years, reaching
37% in men age 70 years or more. CONCLUSIONS: These data confirm that the serum
PSA concentration increases with advancing age in the absence of clinically
evident prostatic malignancy. In younger patients with LUTS, serum PSA variance
with age seems to be less dependent upon the age-related variance in prostate
volume.
PMID- 9650910
TI - Prostate-thyroid axis: stimulatory effects of ventral prostate secretions on
thyroid function.
AB - BACKGROUND: Endocrine cells of the prostate secrete thyrotropin (TSH)-releasing
hormone (TRH), TRH- and TSH-like peptides, and growth factors. Propylthiouracil-
and methimazole-induced hypothyroidism increased prostatic levels of TRH in rats
as in hypothalamus, whereas thyroxine (T4) replacement decreased TRH. From these
reports, we inferred the existence of a prostate-thyroid axis. METHODS: The
influence of the prostate on the thyroid gland was studied in albino rats.
Ventral prostate was surgically removed on day 31 postpartum. The animals were
sacrificed on day 60 postoperation. Serum thyroid hormones were assayed by
radioimmunoassay (RIA). For in vitro studies, normal thyroid and ventral prostate
glands were cocultured with or without thyroid-stimulating hormone (TSH)
antibody, to assess the direct influence of prostatic secretions on thyroid
hormone secretion. RESULTS: Serum total and free T4 and triiodothyronine (T3)
were significantly reduced in ventral prostatectomized rats. Histological
analysis of the thyroid showed that the diameters of the peripheral and middle
follicles, colloid epithelial cells, and nuclei were increased in
prostatectomized rats, indicating hypothyroid status. Total T3 and T4 were
significantly elevated in the culture medium when thyroid and prostate were
cocultured, irrespective of the presence of TSH antibody. CONCLUSIONS: The
present study suggests that ventral prostatic secretions have a stimulatory role
on the thyroid gland.
PMID- 9650911
TI - Effect of bone proteins on human prostate cancer cell lines in vitro.
AB - BACKGROUND: Despite the high incidence and serious consequences of skeletal
metastasis in prostate cancer patients, the mechanisms involved in establishing
secondary lesions in bone are not well-understood. In this study, the role of the
mineralized bone matrix in the process of skeletal metastasis was evaluated.
METHODS: Attachment, migration, and proliferation responses of human prostate
cancer cells to a crude bone protein extract (CBE) were studied. LNCaP and DU145
cells were utilized in 24-hr attachment assays. Boyden chamber chemotactic assays
and cell proliferation assays utilized DU145 cells. RESULTS: CBE and fibronectin
(FN) promoted attachment of DU145 cells, whereas only FN facilitated attachment
of LNCaP cells. CBE-mediated adhesion of DU145 cells was reduced by 94% with
cycloheximide, by 98% with RGD peptides, and by 94% with an antibody to
alphavbeta3. Although DU145 cells migrated toward FN, CBE did not promote
migration of DU145 cells. DU145 cells grown in the presence of CBE-containing
media demonstrated a significant reduction in cell number by day 4. The
antiproliferative effect of CBE was not due to cell toxicity. CONCLUSIONS: In
conclusion, results from this study indicate that mineralized bone proteins
promote the attachment of DU145 cells in vitro and suggest that bone proteins may
play a key role in vivo during the development of metastatic prostate lesions in
bone.
PMID- 9650912
TI - Apoptosis and related genes in the rat ventral prostate following androgen
ablation in response to ethane dimethanesulfonate.
AB - BACKGROUND: Following androgen withdrawal, regression of the prostate is
characterized by apoptotic cell death. The molecular events governing this
process have not been fully characterized. METHODS: Using ethane-1,2
dimethanesulfonate (EDS) to induce androgen ablation, we investigated the role of
the Bcl-2 family members and Fas pathway in this phenomenon. Prostates were
examined from adult male rats injected with 100 mg/kg EDS and killed 2, 5, and 8
days later. RESULTS: Regression of the prostate was evident as a time-dependent
decrease in weight. The number of apoptotic cells identified by in situ end
labeling was maximal after 5 days of treatment. There was no statistically
significant change in the expression of Bax, Bcl-xl, Bcl-2, or p53 following
androgen withdrawal. In contrast, 5 days post-EDS treatment, testosterone
repressed prostate message (TRPM-2) and Fas-R expression were induced. There was
a decline in Fas-L levels 8 days after EDS administration. CONCLUSIONS: This
study extends previous work which has shown that androgen withdrawal induces
apoptosis in the prostate. We have shown that although p53 and the Bcl-2 family
members examined in this study do not seem to be important in this process, the
Fas pathway may play a role in apoptosis of the ventral prostate in response to
androgen ablation.
PMID- 9650913
TI - Chromosome 16q24 deletion and decreased E-cadherin expression: possible
association with metastatic potential in prostate cancer.
AB - BACKGROUND: Deletion of chromosome 16q is a frequent aberration in prostatic
carcinoma, indicating the existence of candidate tumor suppressor genes involved
in the pathogenesis of prostate cancer. METHODS: Chromosome 16 numerical
aberration and loss of 16q were studied by fluorescence in situ hybridization in
31 primary and 22 metastatic tumors from 53 patients. The results were compared
with E-cadherin expression, tumor grade and stage, and DNA ploidy. RESULTS:
Numerical chromosome 16 aberrations, 16q deletion, and loss of E-cadherin
expression were found in 29%, 35%, and 29% of the primary tumors, respectively,
and in 73%, 73%, and 73% of the metastases, respectively. High tumor grade and
DNA aneuploidy were also found to have significant correlation with metastases.
CONCLUSIONS: Deletion of chromosome 16q24 and/or loss of the E-cadherin function
appears in a high frequency in metastases of prostate cancer. The strong
correlations suggest that they may be important risk factors, contributing to the
metastatic potential of the tumor.
PMID- 9650914
TI - Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells
and PSMA peptides.
AB - BACKGROUND: A phase I trial involving patients with advanced prostate cancer was
conducted to assess the safe administration of dendritic cells (DC) and HLA-A0201
specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 or -P2).
Thirty-three of the phase I participants were subsequently enrolled in a phase II
trial, which involved six infusions of DC pulsed with PSM-P1 and -P2 peptides.
METHODS: Clinical monitoring was conducted up to 770 days from the start of the
phase I study. Data collected included: complete blood count, bone and total
alkaline phosphatase, prostate markers, physical examination, performance status,
bone scan, ProstaScint scan, and chest X-ray, as well as assays to monitor
cellular immune responses. RESULTS: Nine partial responders were identified in
the phase II study based on National Prostate Cancer Project (NPCP) criteria,
plus 50% reduction of prostate-specific antigen. Four of the partial responders
were also responders in the phase I study, with an average response duration of
225 days. Their combined average total response period was over 370 days. Five
other responders were nonresponders in the phase I study. Their average partial
response period was 196 days. CONCLUSIONS: The responses observed in the phase I
and II clinical trials were significant and of long duration. The partial
responder group included patients who continued to respond from phase I, as well
as those who started to respond during the phase II trial.
PMID- 9650915
TI - Conference summary: First International Workshop on Animal models of Prostate
Cancer.
PMID- 9650916
TI - Workgroup I: rodent models of prostate cancer.
PMID- 9650917
TI - Workgroup 2: human xenograft models of prostate cancer.
PMID- 9650918
TI - Workgroup 3: transgenic and reconstitution models of prostate cancer.
PMID- 9650919
TI - Workgroup 4: spontaneous prostate carcinoma in dogs and nonhuman primates.
PMID- 9650920
TI - Diagnosis of Q fever.
PMID- 9650921
TI - Monoclonal antibody against Babesia equi: characterization and potential
application of antigen for serodiagnosis.
AB - Monoclonal antibody (MAb) BEG3 was produced against Babesia equi parasites to
define a species-specific antigen for diagnostic use. The MAb reacted with
single, paired, and Maltese cross forms of B. equi, and no reaction was observed
with this MAb on acetone-fixed Babesia caballi, Babesia ovata, or Babesia microti
parasites in the indirect immunofluorescent antibody test. Confocal laser and
immunoelectron microscopic studies showed that the antigen which was recognized
by this MAb was located on the surface of B. equi parasites. This MAb recognized
a 19-kDa protein of B. equi antigen and did not react with B. caballi antigen or
normal horse erythrocytes in immunoblot analysis. This MAb also significantly
inhibited the in vitro growth of the B. equi parasite. Preliminary studies using
partially purified antigen, which was separated by high-pressure liquid
chromatography and recognized by the MAb, suggested that it is a suitable antigen
for enzyme-linked immunosorbent assay detection of anti-B. equi antibodies in
naturally infected horse sera.
PMID- 9650922
TI - Diagnosis of Mycobacterium microti infections among humans by using novel genetic
markers.
AB - As a result of DNA typing of Mycobacterium microti isolates from animals in the
United Kingdom and The Netherlands, we diagnosed four human M. microti
infections. These are the first M. microti infections among humans to be
reported. Three of the patients were immunocompromised and suffered from
generalized forms of tuberculosis. The fourth patient was a 34-year-old
immunocompetent male with a persistent cough and undefined X-ray abnormalities.
Two of the M. microti infections were recognized by their IS6110 restriction
fragment length polymorphism (RFLP) patterns, which showed a high degree of
similarity with those of M. microti strains isolated from a pig and a ferret in
The Netherlands. The two other human M. microti infections were recognized by
using the recently developed DNA fingerprinting method, "spoligotyping," directly
on clinical material. All M. microti isolates from the United Kingdom and The
Netherlands were found to contain an exceptionally short genomic direct repeat
region, resulting in identical two-spacer sequence reactions in spoligotyping. In
contrast, the highly similar IS6110 RFLP patterns of the vole strains from the
United Kingdom differed considerably from the RFLPs of all M. microti strains
isolated in The Netherlands, suggesting that geographic isolation led to
divergent strains in the United Kingdom and on the continent.
PMID- 9650923
TI - Molecular epidemiological study of nosocomial Enterobacter aerogenes isolates in
a Belgian hospital.
AB - In 1995, the rate of isolation of Enterobacter aerogenes in the Saint-Pierre
University Hospital in Brussels, Belgium, was higher than that in the preceding
years. A total of 45 nosocomial E. aerogenes strains were collected from 33
patients of different units during that year, and they were isolated from 19
respiratory specimens, 13 pus specimens, 7 blood specimens, 4 urinary specimens,
1 catheter specimen, and 1 heparin vial. The strains were analyzed to determine
their epidemiological relatedness and were characterized by their antibiotic
resistance pattern determination, plasmid profiling, and genomic fingerprinting
by macrorestriction analysis with pulsed-field gel electrophoresis (PFGE). The
majority of the strains (82%) were multiply resistant to different commonly used
antibiotics. Two major plasmid profiles were found: most strains (64%) harbored
two plasmids of different sizes, whereas the others (20%) contained a single
plasmid. PFGE with SpeI and/or XbaI restriction enzymes revealed that a single
clone (80%) was responsible for causing infections or colonizations throughout
the year, and this result was concordant with those obtained by plasmid
profiling, with slight variations. By comparing the results of these three
methods, PFGE and plasmid profiling were found to be the techniques best suited
for investigating the epidemiological relatedness of E. aerogenes strains, and
they are therefore proposed as useful tools for the investigation of nosocomial
outbreaks caused by this organism.
PMID- 9650924
TI - Characterization of glycopeptide-resistant enterococci from a Swiss hospital.
AB - Between August 1994 and September 1996, 28 glycopeptide-resistant enterococci
(GRE) were isolated from 8 infected patients and 11 intestinal carriers
hospitalized at the University Hospital of Geneva. Identification to the species
was made by both phenotypic (API 20 STREP and Rapid ID 32 STREP systems, and
Vitek Gram Positive Identification Card) and genotypic methods using a multiplex
PCR assay developed also for the determination of the genotype of glycopeptide
resistance (vanA, vanB, vanC1, and vanC2-C3 genes). Fifteen isolates were
identified as Enterococcus faecium, 8 as E. gallinarum, 4 as E. faecalis, and 1
as E. hirae. All of the phenotypic identification methods failed to differentiate
some isolates of E. gallinarum from E. faecium, or vice versa. Both vanA (n = 18)
and vanB (n = 4) glycopeptide resistance genotypes were found. For the first
time, the vanB determinant was found in two isolates of E. gallinarum. Two
patients were colonized by two different species containing the vanA gene and one
by two different species containing the vanB gene. All vanA isolates were highly
resistant to both vancomycin and teicoplanin except for three isolates which were
susceptible to teicoplanin. Molecular typing by pulsed-field gel electrophoresis
showed identical or similar patterns among E. faecium isolates with the vanA gene
in five patients for whom the epidemiological link could not be always
elucidated. This study emphasizes the necessity of utilizing both phenotypic and
genotypic methods to characterize GRE.
PMID- 9650925
TI - Characterization of IS1245 for strain typing of Mycobacterium avium.
AB - IS1245 is an insertion element widely prevalent among isolates of Mycobacterium
avium. We used PvuII Southern blots to analyze IS1245 polymorphisms among 159 M.
avium isolates (141 clinical isolates from 40 human immunodeficiency virus
infected patients plus 18 epidemiologically related environmental isolates) that
represented 40 distinct M. avium strains, as resolved by previous studies by
pulsed-field gel electrophoresis (PFGE). All 40 strains carried DNA homologous to
IS1245 and thus were typeable. Twenty-five (63%) strains had > or = 10 copies of
the element, 6 (15%) had 4 to 9 copies, and 9 (23%) had only 1 to 3 copies. Among
the last group of nine strains (each of which was distinct by PFGE analysis),
IS1245 typing resolved only four patterns and thus provided poor discriminatory
power. To evaluate the in vivo stability of IS1245, we analyzed 32 strains for
which sets of 2 to 19 epidemiologically related isolates were available. For 19
(59%) of these sets, all isolates representing the same strain had
indistinguishable IS1245 patterns. Within eight (25%) sets, one or more isolates
had IS1245 patterns that differed by one or two fragments from the modal pattern
for the isolates of that strain. Five (16%) sets included isolates whose patterns
differed by three or more fragments; on the basis of IS1245 typing those isolates
would have been designated distinct strains. IS1245 was stable during in vitro
passage, suggesting that the variations observed represented natural
translocations of the element. IS1245 provides a useful tool for molecular strain
typing of M. avium but may have limitations for analyzing strains with low copy
numbers or for resolving extended epidemiologic relationships.
PMID- 9650926
TI - Use of multiple competitors for quantification of human immunodeficiency virus
type 1 RNA in plasma.
AB - Quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma has
rapidly become an important tool in basic HIV research and in the clinical care
of infected individuals. Here, a quantitative HIV assay based on competitive
reverse transcription-PCR with multiple competitors was developed. Four RNA
competitors containing identical PCR primer binding sequences as the viral HIV-1
RNA target were constructed. One of the PCR primers was fluorescently labeled,
which facilitated discrimination between the viral RNA and competitor amplicons
by fragment analysis with conventional automated sequencers. The coamplification
of known amounts of the RNA competitors provided the means to establish internal
calibration curves for the individual reactions resulting in exclusion of tube-to
tube variations. Calibration curves were created from the peak areas, which were
proportional to the starting amount of each competitor. The fluorescence
detection format was expanded to provide a dynamic range of more than 5 log
units. This quantitative assay allowed for reproducible analysis of samples
containing as few as 40 viral copies of HIV-1 RNA per reaction. The within- and
between-run coefficients of variation were <24% (range, 10 to 24) and <36%
(range, 27 to 36), respectively. The high reproducibility (standard deviation,
<0.13 log) of the overall procedure for quantification of HIV-1 RNA in plasma,
including sample preparation, amplification, and detection variations, allowed
reliable detection of a 0.5-log change in RNA viral load. The assay could be a
useful tool for monitoring HIV-1 disease progression and antiviral treatment and
can easily be adapted to the quantification of other pathogens.
PMID- 9650927
TI - Detection of Echinococcus multilocularis in the definitive host: coprodiagnosis
by PCR as an alternative to necropsy.
AB - Recently, extensions of the range of Echinococcus multilocularis in Europe and
North America and drastic increases in fox populations in Europe put an
increasing proportion of the human population at risk of alveolar echinococcosis.
To obtain data on the local infection pressure, studies of the prevalence of the
parasite in the animals that transmit the parasite, foxes, dogs, and cats, are
urgently required. Such investigations, however, have been hampered by the need
for necropsy of the host animal to specifically diagnose infection with the
parasite. In this study, a nested PCR and an improved method for DNA extraction
were developed to allow the sensitive and specific diagnosis of E. multilocularis
infections directly from diluted fecal samples from foxes. The target sequence
for amplification is part of the E. multilocularis mitochondrial 12S rRNA gene.
The specificity of the method was 100% when it was tested against 18 isolates
(metacestodes and adult worms) of 11 cestode species, including E. granulosus.
The sensitivity of the method was evaluated by adding egg suspensions and
individual eggs to samples of diluted feces from uninfected foxes. The presence
of one egg was sufficient to give a specific signal. To confirm the PCR results,
an internal probe which hybridized only with E. multilocularis amplification
products but not with the DNA of other cestodes was constructed. In order to
investigate the applicability of this method for epidemiological studies, 250
wild foxes from a area in southern Germany where echinococcosis is highly endemic
were examined by both necropsy and PCR of rectal contents. The sensitivity
correlated with the parasites' number and stage of maturity. It ranged from 100%
(>1,000 gravid worms) to 70% (<10 nongravid worms). On the basis of positive PCR
results for 165 foxes, the sensitivity of the traditional and widely used
necropsy method was found to be not higher than 76%. We therefore present this
PCR system as an alternative method for the routine diagnosis of E.
multilocularis in carnivores.
PMID- 9650928
TI - Use of monoclonal antibodies to identify serotypes of enterovirus isolates.
AB - Nonpoliovirus enteroviruses cause a variety of diseases that are common in young
children and adults. The "gold standard" for laboratory diagnosis of
enteroviruses is cell culture isolation, followed by serotype identification by
neutralization assay. These procedures are time-consuming and expensive. Rapid
serotype identification of enteroviruses is important in differentiating
nonpoliovirus enterovirus pathogens from vaccine strain polioviruses that can be
shed for some time after vaccination. In the present investigation, we evaluated
a rapid method for serotype identification of enteroviruses by indirect
immunofluorescence assay (IFA) using commercially available monoclonal antibodies
for polioviruses, coxsackieviruses type B, and six serotypes of commonly
circulating echoviruses. Of 291 isolates of enteroviruses included in the study,
95 were polioviruses and 196 were nonpoliovirus enteroviruses. Two hundred thirty
four of these (38 polioviruses and 196 nonpoliovirus enteroviruses) were
consecutively grown in the laboratory over a 5-year period. IFA identified the
serotypes of 74% of the consecutive isolates and 71% of all enterovirus isolates
by yielding a positive staining result. The levels of agreement in the
identification of the enterovirus group between IFA and neutralization tests were
92% for consecutively grown isolates and 85% for all enterovirus isolates. The
sensitivity of the IFA for the detection of viruses for which specific monoclonal
antibodies were applied was 73% for polioviruses, 85% for coxsackieviruses type
B, and 94% for echoviruses. Specificity was near 100% for polioviruses and
coxsackieviruses type B and 94% for echoviruses. We conclude that IFA can be
helpful as a preliminary test for serotype identification of enteroviruses. The
results are most accurate when the test identifies the isolate as a poliovirus.
PMID- 9650929
TI - Determination of types of Enterocytozoon bieneusi strains isolated from patients
with intestinal microsporidiosis.
AB - To determine the types of Enterocytozoon bieneusi strains associated with
intestinal microsporidiosis, we developed a rapid and efficient approach for
typing parasites obtained from stool specimens by PCR-restriction fragment length
polymorphism (PCR-RFLP). Typing was based on DNA polymorphism of the ribosomal
DNA internal transcribed spacer (ITS) region of E. bieneusi. RFLPs generated with
two restriction enzymes (NlaIII and Fnu4HI) in PCR-amplified ITS products were
used to classify strains into different lineages. This approach was successfully
used to differentiate 78 strains that had been obtained from the stools of 65
patients with intestinal microsporidiosis. Among the 78 strains, we found four
genetically unrelated lineages, showing the genetic diversity of E. bieneusi.
Type I strains of E. bieneusi were found in a majority of the samples, accounting
for 51 (78%) of the 65 microsporidiosis cases. In contrast, type II, III, and IV
strains were found in only 8 (12%), 3 (5%), and 3 (5%) cases, respectively. All
strains of E. bieneusi we have tested so far fall into one of four different
lineages, and this study shows that human intestinal microsporidiosis is most
often associated with type I strains. PCR-RFLP analysis of the ITS region of E.
bieneusi should be useful for epidemiological studies.
PMID- 9650930
TI - International surveillance of bloodstream infections due to Candida species:
frequency of occurrence and antifungal susceptibilities of isolates collected in
1997 in the United States, Canada, and South America for the SENTRY Program. The
SENTRY Participant Group.
AB - An international program of surveillance of bloodstream infections (BSIs) in the
United States, Canada, and South America between January and December 1997
detected 306 episodes of candidemia in 34 medical centers (22 in the United
States, 6 in Canada, and 6 in South America). Eighty percent of the BSIs were
nosocomial and 50% occurred in patients hospitalized in an intensive care unit.
Overall, 53.3% of the BSIs were due to Candida albicans, 15.7% were due to C.
parapsilosis, 15.0% were due to C. glabrata, 7.8% were due to C. tropicalis, 2.0%
were due to C. krusei, 0.7% were due to C. guilliermondii, and 5.8% were due to
Candida spp. However, the distribution of species varied markedly by country. In
the United States, 43.8% of BSIs were due to non-C. albicans species. C. glabrata
was the most common non-C. albicans species in the United States. The proportion
of non-C. albicans BSIs was slightly higher in Canada (47.5%), where C.
parapsilosis, not C. glabrata, was the most common non-C. albicans species. C.
albicans accounted for 40.5% of all BSIs in South America, followed by C.
parapsilosis (38.1%) and C. tropicalis (11.9%). Only one BSI due to C. glabrata
was observed in South American hospitals. Among the different species of Candida,
resistance to fluconazole (MIC, > or = 64 microg/ml) and itraconazole (MIC, > or
= 1.0 microg/ml) was observed with C. glabrata and C. krusei and was observed
more rarely among other species. Isolates of C. albicans, C. parapsilosis, C.
tropicalis, and C. guilliermondii were all highly susceptible to both fluconazole
(99.4 to 100% susceptibility) and itraconazole (95.8 to 100% susceptibility). In
contrast, 8.7% of C. glabrata isolates (MIC at which 90% of isolates are
inhibited [MIC90], 32 microg/ml) and 100% of C. krusei isolates were resistant to
fluconazole, and 36.9% of C. glabrata isolates (MIC90, 2.0 microg/ml) and 66.6%
of C. krusei isolates were resistant to itraconazole. Within each species there
were no geographic differences in susceptibility to fluconazole or itraconazole.
PMID- 9650931
TI - Rapid detection of Chlamydia pneumoniae by PCR-enzyme immunoassay.
AB - Chlamydia pneumoniae is an important human respiratory pathogen. Laboratory
diagnosis of infection with this organism is difficult. To facilitate the
detection of C. pneumoniae by PCR, an enzyme immunoassay (EIA) for analysis of
PCR products was developed. Biotin-labeled PCR products generated from the 16S
rRNA gene of C. pneumoniae were hybridized to a digoxigenin-labeled probe and
then immobilized to streptavidin-coated microtiter plates. Bound PCR product
probe hybrids were detected with antidigoxigenin peroxidase conjugate and a
colorimetric substrate. This EIA was as sensitive as Southern blot hybridization
for the detection of PCR products and 100 times more sensitive than visualization
of PCR products on agarose gels. The diagnostic value of the PCR-EIA in
comparison to cell culture was assessed in throat swab specimens from children
with respiratory tract infections. C. pneumoniae was isolated from only 1 of 368
specimens tested. In contrast, 15 patient specimens were repeatedly positive for
C. pneumoniae by PCR and Southern analysis. All of these 15 specimens were also
identified by PCR-EIA. Of the 15 specimens positive by 16S rRNA-based PCR, 13
specimens could be confirmed by omp1-based PCR or direct fluorescent-antibody
assay. Results of this study demonstrate that PCR is more sensitive than cell
culture for the detection of C. pneumoniae. The EIA described here is a rapid,
sensitive, and simple method for detection of amplified C. pneumoniae DNA.
PMID- 9650932
TI - Algorithmic approach to high-throughput molecular screening for alpha interferon
resistant genotypes in hepatitis C patients.
AB - This study was designed to analyze the feasibility and validity of using Cleavase
Fragment Length Polymorphism (CFLP) analysis as an alternative to DNA sequencing
for high-throughput screening of hepatitis C virus (HCV) genotypes in a high
volume molecular pathology laboratory setting. By using a 244-bp amplicon from
the 5' untranslated region of the HCV genome, 61 clinical samples received for
HCV reverse transcription-PCR (RT-PCR) were genotyped by this method. The
genotype frequencies assigned by the CFLP method were 44.3% for type 1a, 26.2%
for 1b, 13.1% for type 2b, and 5% type 3a. The results obtained by nucleotide
sequence analysis provided 100% concordance with those obtained by CFLP analysis
at the major genotype level, with resolvable differences as to subtype
designations for five samples. CFLP analysis-derived HCV genotype frequencies
also concurred with the national estimates (N. N. Zein et al., Ann. Intern. Med.
125:634-639, 1996). Reanalysis of 42 of these samples in parallel in a different
research laboratory reproduced the CFLP fingerprints for 100% of the samples.
Similarly, the major subtype designations for 19 samples subjected to different
incubation temperature-time conditions were also 100% reproducible. Comparative
cost analysis for genotyping of HCV by line probe assay, CFLP analysis, and
automated DNA sequencing indicated that the average cost per amplicon was lowest
for CFLP analysis, at $20 (direct costs). On the basis of these findings we
propose that CFLP analysis is a robust, sensitive, specific, and an economical
method for large-scale screening of HCV-infected patients for alpha interferon
resistant HCV genotypes. The paper describes an algorithm that uses as a reflex
test the RT-PCR-based qualitative screening of samples for HCV detection and also
addresses genotypes that are ambiguous.
PMID- 9650933
TI - Identification and molecular characterization of beta-hemolytic streptococci
isolated from harbor porpoises (Phocoena phocoena) of the North and Baltic Seas.
AB - The present study was designed to identify and comparatively investigate 35 beta
hemolytic streptococci isolated from stranded harbor porpoises or from animals
caught in fishing nets of the North and Baltic seas. According to biochemical and
serological data and to lectin agglutination tests with the lectin of Arachis
hypogaea, all 35 isolates could be classified in Lancefield's serological group L
and could be identified as Streptococcus dysgalactiae subsp. dysgalactiae. All 35
group L streptococci were uniformly sensitive to most of the antibiotics tested.
To further analyze the epidemiological relationship, the isolates were subjected
to macrorestriction analysis of their chromosomal DNA by pulsed-field gel
electrophoresis. Digestion of the chromosomal DNA with the restriction enzymes
SmaI and ApaI revealed that most of the group L streptococci seemed to be
apparently identical or related. These results indicate that one clone or at
least related group L streptococcal clones play an important role for infections
of harbor porpoises of the North and Baltic seas. This might possibly be caused
by a direct transfer of the bacteria from animal to animal.
PMID- 9650934
TI - Effects of different test conditions on MICs of food animal growth-promoting
antibacterial agents for enterococci.
AB - The influence of the addition of sheep blood to Mueller-Hinton II agar and the
effects of aerobic incubation with or without CO2 and of anaerobic incubation
were tested with bacitracin, tylosin, avoparcin, virginiamycin, avilamycin,
narasin, and flavomycin on enterococci. The antibacterial activity of bambermycin
(Flavomycin) was strongly inhibited by the addition of blood, except with the
species Enterococcus faecium, Enterococcus mundtii, Enterococcus hirae,
Enterococcus casseliflavus, and Enterococcus gallinarum, which were not
susceptible to this antibiotic on blood-free medium. With all other
antimicrobials except avoparcin and tylosin, the presence of blood resulted in
MIC increases of 1 to 3 log2 differences. Incubation in aerobic or anaerobic
atmospheres enriched with CO2 lowered the susceptibility of enterococci to
tylosin and increased their susceptibility to avilamycin, narasin, and avoparcin.
This effect was most pronounced in tests on blood-free media. Results of
susceptibility tests incubated under anaerobiosis and in a CO2-enriched
atmosphere did not differ. For all enterococcal species, the preferred conditions
for testing the susceptibility are Mueller-Hinton II medium supplemented with
blood and incubation in a CO2-enriched atmosphere. However, when only E. faecium
and Enterococcus faecalis are being tested, Mueller-Hinton II medium without
blood incubated aerobically gives satisfactory results.
PMID- 9650936
TI - Use of lambda phage DNA as a hybrid internal control in a PCR-enzyme immunoassay
to detect Chlamydia pneumoniae.
AB - An inherent problem in the diagnostic PCR assay is the presence of ill-defined
inhibitors of amplification which may cause false-negative results. Addition of
an amplifiable fragment of foreign DNA in the PCR to serve as a hybrid internal
control (HIC) would allow for a simple way to identify specimens containing
inhibitors. Two oligonucleotide hybrid primers were synthesized to contain
nucleic acid sequences of the Chlamydia pneumoniae 16S rRNA primers in a position
flanking two primers that target the sequences of a 650-bp lambda phage DNA
segment. By using the hybrid primers, hybrid DNA comprising a large sequence of
lambda phage DNA flanked by short pieces of chlamydia DNA was subsequently
generated by PCR, cloned into a plasmid vector, and purified. Plasmids containing
the hybrid DNA were diluted and used as a HIC by adding them to each C.
pneumoniae PCR test. Consequently, C. pneumoniae primers were able to amplify
both chlamydia DNA and the HIC DNA. The production of a 689-bp HIC DNA band on an
acrylamide gel indicated that the specimen contained no inhibitors and that
internal conditions were compatible with PCR. Subsequently, a biotinylated RNA
probe for the HIC was transcribed from a nested sequence of the HIC and was used
for its hybridization. Detection of the HIC DNA-RNA hybrid was achieved by enzyme
immunoassay (EIA). This PCR-EIA system with a HIC was initially tested with 12
previously PCR-positive and 14 previously PCR-negative specimens. Of the 12 PCR
positive specimens, 11 were reconfirmed as positive; 1 had a negative HIC value,
indicating inhibition. Of the 14 previously PCR-negative specimens, 13 were
confirmed as true negative; 1 had a negative HIC value, indicating inhibition.
The assay was then used with 237 nasopharyngeal specimens from patients with
pneumonia. Twenty-one of 237 (8.9%) were positive for C. pneumoniae, and 42
(17.7%) were found to inhibit the PCR. Specimens showing inhibitory activity were
diluted 1:10 and were retested. Ten specimens were still inhibitory to the PCR
and required further DNA purification. No additional positive samples were
detected and 3 nasopharyngeal specimens remained inhibitory to PCR.
Coamplification of a HIC DNA can help confirm true-negative PCR results by ruling
out the presence of inhibitors of DNA amplification.
PMID- 9650935
TI - Antigenic and molecular characterization of wild type 1 poliovirus causing
outbreaks of poliomyelitis in Albania and neighboring countries in 1996.
AB - Mass vaccination has led poliomyelitis to become a rare disease in a large part
of the world, including Western Europe. However, in the past 20 years wild
polioviruses imported from countries where polio is endemic have been responsible
for outbreaks in otherwise polio-free European countries. We report on the
characterization of poliovirus isolates from a large outbreak of poliomyelitis
that occurred in Albania in 1996 and that also spread to the neighboring
countries of Yugoslavia and Greece. The epidemics involved 145 subjects, mostly
young adults, and caused persisting paralysis in 87 individuals and 16 deaths.
The agent responsible for the outbreak was isolated from 74 patients and was
identified as wild type 1 poliovirus by both immunological and molecular methods.
Sequence analysis of the genome demonstrated the involvement of a single virus
strain throughout the epidemics, and genotyping analysis showed 95% homology of
the strain with a wild type 1 poliovirus strain isolated in Pakistan in 1995.
Neutralization assays with both human sera and monoclonal antibodies were
performed to analyze the antigenic structure of the epidemic strain, suggesting
its peculiar antigenic characteristics. The presented data underline the current
risks of outbreaks due to imported wild poliovirus and emphasize the need to
improve vaccination efforts and also the need to implement surveillance in
countries free of indigenous wild poliovirus.
PMID- 9650937
TI - Blood cultures positive for coagulase-negative staphylococci: antisepsis,
pseudobacteremia, and therapy of patients.
AB - A blood culture cohort study investigating issues related to isolation of
coagulase-negative staphylococci (CoNS) and other skin microflora is reported.
Data were collected over 12 weeks to determine the incidence of significant CoNS
bacteremia versus that of pseudobacteremia (contaminants) and to evaluate drug
therapy in patients with cultures positive for CoNS. In addition, the
effectiveness of 0.2% chlorine peroxide as a bactericidal disinfectant was
compared to that of 10% providone iodine. A total of 3,276 cultures of blood from
1,433 patients were evaluated in the study. Eighty-nine cultures were positive
for skin flora, with 81 of 89 (91%) involving CoNS. The incidence of significant
CoNS bacteremia was 20 of 81 (24.7%), that of indeterminate bacteremia was 10 of
81 (12.3%), and that of contamination was 59 of 81 (72.8%). The incidence of
significant bacteremia involving CoNS was double the 10 to 12% rate based on
previous estimations at our institutions. In tests with the two bactericidal
disinfectants, 22 of 1,639 cultures (1.3%) in the chlorine peroxide group versus
37 of 1,637 (2.3%) in the providone iodine group were considered contaminated (P
= 0.065). Rates of contamination for venipuncture versus catheter collection were
not significantly different (P = 0.46). The overall contamination rate was 59 of
3,276 (1.8%), which is consistent with the lower end of published quality
assurance benchmark standards. The low rate was believed to be due to the
professional phlebotomy staff in our institutions. There was excellent agreement
between retrospective analysis by reviewers, when formal criteria were used, and
the attending physicians' intuitive clinical impressions in the classification of
significant bloodstream infections (100% agreement) or contamination (95%
agreement). However, physicians still used antimicrobial agents to treat nearly
one-half of the patients with contaminated blood cultures, with vancomycin being
misused in 34% of patients. In addition, 10% of patients with significant
bacteremia were treated with inappropriate agents. There were no significant
adverse events or prolonged hospital stays due to the unnecessary use of
vancomycin; however, the additional costs of treating patients whose cultures
contained CoNS contaminants was estimated to be $1,000 per patient. Measures to
limit the unnecessary use of vancomycin (and other agents) are important.
PMID- 9650938
TI - Molecular characterization of vancomycin-resistant enterococci from hospitalized
patients and poultry products in The Netherlands.
AB - Vancomycin-resistant enterococci (VRE) pose an emerging health risk, but little
is known about the precise epidemiology of the genes coding for vancomycin
resistance. To determine whether the bacterial flora of consumer poultry serves
as a gene reservoir, the level of contamination of poultry products with VRE was
determined. VRE were genotyped by pulsed-field gel electrophoresis (PFGE), and
transposon structure mapping was done by PCR. The vanX-vanY intergenic regions of
several strains were further analyzed by sequencing. A total of 242 of 305 (79%)
poultry products were found to be contaminated with VRE. Of these VRE, 142 (59%)
were high-level-vancomycin-resistant Enterococcus faecium strains (VREF). PFGE
revealed extensive VREF heterogeneity. Two genotypes were found nationwide on
multiple occasions: type A (22 of 142 VREF [15%]) and type B (14 of 142 VREF
[10%]). No PFGE-deduced genetic overlap was found when VREF from humans were
compared with VREF from poultry. Two vanA transposon types were identified among
poultry strains. In 59 of 142 (42%) of the poultry VREF, the size of the
intergenic region between vanX and vanY was approximately 1,300 bp. This
transposon type was not found in human VREF. In contrast, all human strains and
83 of 142 (58%) of the poultry VREF contained an intergenic region 543 bp in
size. Sequencing of this 543-bp intergenic vanX-vanY region demonstrated full
sequence conservation. Though preliminary, these data suggest that dissemination
of the resistance genes carried on transposable elements may be of greater
importance than clonal dissemination of resistant strains. This observation is
important for developing strategies to control the spread of glycopeptide
resistance.
PMID- 9650939
TI - Extremely high prevalence of nasopharyngeal carriage of penicillin-resistant
Streptococcus pneumoniae among children in Kaohsiung, Taiwan.
AB - Resistance (intermediate and high) to penicillin among Streptococcus pneumoniae
strains is an emerging problem worldwide. From 1995 to 1997, isolates of S.
pneumoniae not susceptible to penicillin were seen with increasing frequency from
blood, cerebrospinal fluid, pleural fluid, and middle ear fluid from pediatric
patients at the Veterans General Hospital-Kaohsiung. To determine the prevalence
of carriage of these penicillin-nonsusceptible S. pneumoniae isolates, we
obtained nasopharyngeal swab specimens from 2,905 children (ages, 2 months to 7
years) attending day-care centers or kindergartens or seen in our outpatient
clinic. S. pneumoniae was isolated from 611 children, and 584 strains were
available for analysis. The oxacillin disc test was used as a screening test to
evaluate penicillin susceptibility. The MICs of 11 antibiotics (penicillin,
cefaclor, cefuroxime, ceftriaxone, cefotaxime, imipenem, chloramphenicol,
clarithromycin, rifampin, vancomycin, and teicoplanin) were determined by the E
test. Only 169 (29%) of the strains were susceptible to penicillin; 175 (30%)
strains were intermediately resistant and 240 (41%) were highly resistant. The
isolates also demonstrated high rates of resistance to other beta-lactams (46%
were resistant to cefaclor, 45% were resistant to cefuroxime, 45% were resistant
to ceftriaxone, 31% were resistant to cefotaxime, and 46% were resistant to
imipenem). The rate of resistance to macrolide antimicrobial agents was
strikingly high; 95% of the isolates were not susceptible to clarithromycin.
However, 97% were susceptible to rifampin and 100% were susceptible to the two
glycopeptides (vancomycin and teicoplanin). While reports of penicillin-resistant
S. pneumoniae increased worldwide through the 1980s, the high prevalence (71%) of
resistance reported here is astonishing. Surveillance of nasopharyngeal swab
specimen cultures may provide useful information on the prevalence of
nonsusceptible strains causing invasive disease. Such information could be used
to guide therapy of pneumococcal infections.
PMID- 9650940
TI - Survival of Acinetobacter baumannii on dry surfaces: comparison of outbreak and
sporadic isolates.
AB - Acinetobacter spp. are important nosocomial pathogens reported with increasing
frequency in outbreaks of cross-infection during the past 2 decades. The majority
of such outbreaks are caused by Acinetobacter baumannii. To investigate whether
desiccation tolerance may be involved in the ability of certain strains of A.
baumannii to cause hospital outbreaks, a blind study was carried out with 39
epidemiologically well-characterized clinical isolates of A. baumannii for which
survival times were determined under simulated hospital conditions. The survival
times on glass coverslips of 22 strains isolated from eight well-defined hospital
outbreaks in a German metropolitan area were compared with the survival times of
17 sporadic strains not involved in outbreaks but rather isolated from inpatients
in the same geographic area. All sporadic isolates have been shown by pulsed
field gel electrophoresis to represent different strain types. There was no
statistically significant difference between the survival times of sporadic
strains of A. baumannii and outbreak strains (27.2 versus 26.5 days,
respectively; P < or = 0.44) by the Wilcoxon-Mann-Whitney test. All investigated
A. baumannii strains, irrespective of their areas of endemicity or epidemic
occurrence, have the ability to survive for a long time on dry surfaces.
Antimicrobial susceptibility testing showed that A. baumannii outbreak strains
were significantly more resistant to various broad-spectrum antimicrobial agents
than sporadic strains. Both desiccation tolerance and multidrug resistance may
contribute to their maintenance in the hospital setting and may explain in part
their propensity to cause prolonged outbreaks of nosocomial infection.
PMID- 9650941
TI - Epidemiological and environmental investigations of Legionella pneumophila
infection in cattle and case report of fatal pneumonia in a calf.
AB - A fatal pneumonia due to Legionella pneumophila was diagnosed in a young calf
reared in a dairy herd located in northern Italy. Clinical symptoms consisted of
watery diarrhea, hyperthermia, anorexia, and severe dyspnea. The pathological and
histological findings were very similar to those observed in human legionellosis.
Legionella pneumophila serogroup 1 (SG1) and SG10 were isolated from the calfs
lung, and L. pneumophila SG1 was isolated from the calfs liver. L. pneumophila
SG1 was also demonstrated in the lung tissue by immunofluorescence and
immunohistochemical examinations. Nine of 10 L. pneumophila SG1 isolates belonged
to the Olda subtype, and 1 belonged to the Camperdown subtype. A very low
prevalence of antibodies to Legionella was detected in cows and calves reared in
the same herd. Cultures of aqueous sediment of an old electric water heater which
supplied hot water for the feeding of the calves yielded L. pneumophila SG1. Four
of the colonies tested belonged to the Olda subtype. Ten clinical and four
environmental isolates were examined for the presence of plasmids. Nine of them
were also examined by pulsed-field gel electrophoresis assay, and the same
patterns were found for L. pneumophila SG1 Olda strains isolated from the calf
and from the electric heater. This is the first report of a documented case of a
naturally occurring Legionella pneumonia in an animal. Cattle probably act as
accidental hosts for legionellae, much the same as humans.
PMID- 9650942
TI - Evaluation of the VITEK 2 system for rapid identification of medically relevant
gram-negative rods.
AB - The new VITEK 2 system (bioMerieux) was evaluated at two independent sites with
the identification card for gram-negative bacilli (ID-GNB card). Of the 845
strains tested, which represented 70 different taxa belonging to either the
family Enterobacteriaceae or the nonenteric bacilli, 716 (84.7%) were correctly
identified at the species level. Thirty-two (3.8%) additional strains were
identified to the species level after the performance of simple, rapid manual
tests (oxidase, hemolysis, indole reaction, motility, and pigmentation). For 80
(9.5%) strains, these additional tests did not lead to an identification at the
species level but the correct species identification was given among the
organisms listed. Only 7 (0.8%) strains were misidentified, and 10 (1.2%) were
not identified. Mistakes were randomly distributed over different taxa. Due to
the new, more sensitive fluorescence-based technology of the VITEK 2 system,
final results were available after 3 h. Since our evaluation was mainly a stress
test, it is predicted that the VITEK 2 system in conjunction with the ID-GNB card
would perform well under conditions of a routine clinical laboratory in
identifying members of the family Enterobacteriaceae and selected species of
nonenteric bacteria. This system is a promising, highly automated new tool for
the rapid identification of gram-negative bacilli from human clinical specimens.
PMID- 9650943
TI - Molecular epidemiology of Stenotrophomonas maltophilia isolated from clinical
specimens from patients with cystic fibrosis and associated environmental
samples.
AB - Stenotrophomonas maltophilia was isolated from the respiratory tracts of 41 (25%)
of 163 children attending our pediatric cystic fibrosis unit between September
1993 and December 1995. The extents of S. maltophilia contamination of
environmental sites frequented by these patients were investigated with a
selective medium incorporating vancomycin, imipenem, and amphotericin B. Eighty
two isolates of S. maltophilia were cultured from 67 different environmental
sites sampled between January and July 1996. The organism was widespread in the
home environment, with 20 (36%) and 25 (42%) of sampled sites positive in the
homes of colonized and noncolonized patients, respectively. In the nosocomial
setting, it was isolated from 18 (32%) sites in the hospital ward and from 4
(17%) sites in the outpatient clinic area. The most common sites of contamination
were sink drains, faucets, and other items frequently in contact with water. All
environmental and clinical isolates were genotyped with enterobacterial
repetitive intergenic consensus sequences as primers. A total of 33 of the 41
patients were colonized with unique strains, and four pairs of patients shared
strains. Further characterization by pulsed-field gel electrophoresis after
digestion with XbaI found that there was no evidence of patient-to-patient
transmission; however, there was some evidence that a small number of patients
may have acquired the organism from the hospital environment. Resampling of
environmental sites in the hospital ward in January 1997 revealed evidence of
genetic drift, complicating the accurate determination of environmental sources
for clinical strains. The source of the majority of S. maltophilia strains
colonizing the respiratory tracts of these patients with cystic fibrosis remained
uncertain but may have represented multiple, independent acquisitions from a
variety of environmental sites both within and outside the hospital.
PMID- 9650944
TI - Cytoplasmic, nuclear, and platelet autoantibodies in human granulocytic
ehrlichiosis patients.
AB - Serum samples from patients with confirmed human granulocytic ehrlichiosis (HGE)
were tested for cytoplasmic, nuclear, and platelet autoantibodies and rheumatoid
factor. The indirect fluorescence antinuclear antibody test on Hep-2 cells
demonstrated antinuclear titers of > or = 40 and > or = 160 in 44 and 10%,
respectively, of serum samples from HGE patients. Two patients (4%) had
anticytoplasmic (mitochondrial and spindle apparatus) antibodies with a titer of
80 and two patients (4%) had anticytoplasmic (mitochondrial) antibodies with a
titer of 160 or greater. Flow cytometry was used to demonstrate antiplatelet
antibodies in 80% of first serum samples from HGE patients. Rheumatoid factor was
not detected. Nuclear and cytoplasmic autoantibodies are a major cause of
interference when the indirect fluorescence antibody test is used to detect
fluorescence of morulae in Ehrlichia-infected equine neutrophils or HL-60
promyelocytes. Antiplatelet antibodies may contribute to the profound
thrombocytopenia which is a characteristic laboratory feature during the acute
phase of HGE infection. Whether autoantibodies precede infection or are caused by
immune activation of HGE deserves further study.
PMID- 9650945
TI - Comparison of the ABI 7700 system (TaqMan) and competitive PCR for quantification
of IS6110 DNA in sputum during treatment of tuberculosis.
AB - Mycobacterium tuberculosis can persist in sputum for long periods of time after
the initiation of antituberculosis chemotherapy. The purpose of this study was to
determine whether quantitative estimates of M. tuberculosis DNA in sputum
correlate with the numbers of viable bacilli and thus measure the therapeutic
response of patients during treatment. Two methods of M. tuberculosis DNA
quantification were examined by using DNA isolated from sputum specimens serially
collected during the course of chemotherapy. A competitive PCR assay was compared
to an automated system of real-time quantification with the ABI Prism 7700
Sequence Detection System (TaqMan). The ABI 7700 system uses standard PCR in
conjunction with a fluorogenic probe in which the intensity of fluorescence is
proportional to the amount of target DNA present. The results showed that both
PCR systems are reproducible and accurate. The amounts of M. tuberculosis DNA
quantified in sputum corresponded well with the numbers of acid-fast bacilli
(AFB) counted by microscopy. Before initiation of antituberculosis therapy,
measures of AFB, M. tuberculosis DNA, and cultivable bacilli were similar,
suggesting that quantification of DNA is a good method for measuring the initial
bacillary load. However, the rate of disappearance of both AFB and M.
tuberculosis DNA did not correlate with the decline in cultivable bacilli in the
specimen; therefore, these tests are not appropriate for monitoring treatment
efficacy.
PMID- 9650946
TI - Comparison of three molecular assays for rapid detection of rifampin resistance
in Mycobacterium tuberculosis.
AB - Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is an emerging problem of
great importance to public health, with higher mortality rates than drug
sensitive TB, particularly in immunocompromised patients. MDR-TB patients require
treatment with more-toxic second-line drugs and remain infectious for longer than
patients infected with drug-sensitive strains, incurring higher costs due to
prolonged hospitalization. It is estimated that 90% of United Kingdom rifampin
resistant isolates are also resistant to isoniazid, making rifampin resistance a
useful surrogate marker for multidrug resistance and indicating that second- and
third-line drugs to which these isolates are susceptible are urgently required.
Resistance in approximately 95% of rifampin-resistant isolates is due to
mutations in a 69-bp region of the rpoB gene, making this a good target for
molecular genotypic diagnostic methods. Two molecular assays, INNO-LiPA Rif.TB
(Innogenetics, Zwijndrecht, Belgium) and MisMatch Detect II (Ambion, Austin,
Tex.), were performed on primary specimens and cultures to predict rifampin
resistance, and these methods were compared with the resistance ratio method. A
third method, the phenotypic PhaB assay, was also evaluated in comparison to
cultures in parallel with the genotypic assays. In an initial evaluation 16 of
16, 15 of 16, and 16 of 16 rifampin-resistant cultures (100, 93.8, and 100%,
respectively), were correctly identified by line probe assay (LiPA), mismatch
assay, and PhaB assay, respectively. Subsequently 38 sputa and bronchealveolar
lavage specimens and 21 isolates were received from clinicians for molecular
analysis. For the 38 primary specimens the LiPA and mismatch assay correlated
with culture and subsequent identification and susceptibility tests in 36 and 38
specimens (94.7 and 100%), respectively. For the 21 isolates submitted by
clinicians, both assays correlated 100% with routine testing.
PMID- 9650947
TI - Evaluation of intestinal protozoan morphology in human fecal specimens preserved
in EcoFix: comparison of Wheatley's trichrome stain and EcoStain.
AB - As a result of disposal problems related to the use of mercury compounds, many
laboratories have switched from mercuric chloride-based Schaudinn's and polyvinyl
alcohol (PVA) stool preservatives to other, non-mercury-based preservatives. A
comparison of organism recoveries and morphologies of the intestinal protozoa was
undertaken with PVA containing the EcoFix zinc-based Schaudinn's preservative
(Meridian Diagnostics, Inc.); both Wheatley's modification of Gomori's trichrome
stain (WT) and EcoStain (ES) were used to stain 51 human fecal specimens.
Morphology, clarity of nuclear and cytoplasmic detail, overall color differences,
and the ease or difficulty in detecting intestinal protozoa in fecal debris were
assessed for the two permanent stained smears. Overall, organism morphology of
the intestinal protozoa stained with WT and that of protozoa stained with ES were
not equal in nuclear and cytoplasmic detail or range of color. However, the same
organisms were identified in stained fecal smears with either WT or ES, with the
exception of situations in which organism numbers were characterized as rare.
Included were 67 protozoan challenges (number of organisms): Entamoeba
histolytica-Entamoeba dispar (5), Entamoeba coli (9), Entamoeba hartmanni (6),
Endolimax nana (12), Iodamoeba butschlii (8), Blastocystis hominis (19), Giardia
lamblia (6), Dientamoeba fragilis (2), yeast (2), and leukocytes (2). Five
specimens were negative for parasites but contained fecal debris that was
compared for morphologic detail and color range. The ES produces a more gray
green monotone with very little pink or red tone; contrast among the various
colors is less than that seen with WT. Stain intensity for all organisms was
acceptable, and there were no problems with stain deposition. The quality of the
protozoan morphology with ES was often comparable to that with WT (36 of 67
[53.7%]) and, in some cases, better (24 of 67 [35.8%]). Organisms on the WT
stained smear exhibited better morphology in a few instances (4 of 67 [6%]), and
in three instances, there were discrepant organism numbers.
PMID- 9650948
TI - Genetic diversity among strains of Moraxella catarrhalis: analysis using multiple
DNA probes and a single-locus PCR-restriction fragment length polymorphism
method.
AB - Moraxella (Branhamella) catarrhalis, a causative agent of otitis media,
sinusitis, and exacerbation of bronchitis, has acquired widespread ability to
produce beta-lactamase and can be nosocomially transmitted. The typing methods
used in epidemiological analyses of M. catarrhalis are not optimal for genetic
analyses. Two methods, a multiple-locus Southern blot (SB) method and a single
locus PCR-restriction fragment length polymorphism (RFLP) method, were developed
and used to assess genetic diversity and potential clinical and geographic
relationships in M. catarrhalis. Nine randomly cloned M. catarrhalis DNA
fragments were used as probes of SBs containing DNA from 54 geographically and
clinically diverse strains. For comparison, a PCR-RFLP method was developed as a
quick, inexpensive, and discriminating alternative. A highly variable 3.7-kb
genomic region (M46) was cloned and sequenced, and 3.5 kb of the cloned DNA was
targeted for PCR amplification. DNAs from the 54 strains were subjected to PCR
RFLP. SB analysis distinguished all strains that had no apparent epidemiological
linkage (40 of 54), and PCR-RFLP distinguished fewer strains (21 of 54).
Epidemiologically linked strains appeared genetically identical by both methods.
PCR-RFLP was compared to pulsed-field gel electrophoresis (PFGE) for 8 of the 54
strains and 23 additional strains. PCR-RFLP distinguished fewer strains than PFGE
typing (16 of 31 versus 20 of 31 strains), but PCR-RFLP was more useful for
inferring interstrain relatedness. Separate cluster analyses of multilocus SB and
single locus PCR-RFLP data showed high genetic diversity within and across
geographic locations and clinical presentations. The resultant dendrograms were
not entirely concordant, but both methods often gave similar strain clusters at
the terminal branches. High genetic diversity, nonconcordance of cluster analyses
from different genetic loci, and shared genotypes among epidemiologically linked
strains support a hypothesis of high recombination relative to spread of clones.
Single-locus PCR-RFLP may be suitable for short-term epidemiological studies, but
the SB data demonstrate that greater strain discrimination may be obtained by
sampling variation at multiple genomic sites.
PMID- 9650949
TI - Detection of Mycoplasma hyopneumoniae in bronchoalveolar lavage fluids of pigs by
PCR.
AB - In the present investigation we developed a method for the detection of
Mycoplasma hyopneumoniae in bronchoalveolar lavage fluid (BALF) of pigs by PCR
with a primer pair flanking a DNA fragment of 853 bp specific for M.
hyopneumoniae. Several methods were tested to eliminate the amplification
inhibitors present in BALFs. The best results were obtained by the extraction of
the DNA from the BALFs. By the PCR performed with the extracted DNA, 10(2) CFU of
M. hyopneumoniae could be detected in 1 ml of BALF from specific-pathogen-free
swine experimentally inoculated with M. hyopneumoniae. DNA from 11 other
mycoplasma species and 17 cell-walled bacterial species colonizing the
respiratory tracts of pigs was not amplified. In a field study BALFs from 40 pigs
from farms with a history of chronic pneumonia were tested for M. hyopneumoniae
by cultivation and by PCR (i) with BALFs incubated in Friis medium and (ii) with
DNA extracted from the BALFs. In addition, PCR was performed with postmortem lung
washings from 19 of the 40 pigs, and immunofluorescence tests were carried out
with sections of lungs from 18 of the 40 pigs. M. hyopneumoniae could not be
detected in 18 of the 40 pigs by any of the five methods tested. The remaining 22
pigs showed a positive reaction by the PCR with DNA extracted from the BALFs and
variable positive reactions by the other tests. A complete correspondence could
be observed between the immunofluorescence test result and the result of PCR with
DNA. The investigation shows that the PCR with DNA extracted from BALFs is a
suitable technique for the sensitive and specific in vivo detection of M.
hyopneumoniae.
PMID- 9650950
TI - Single-step multiplex PCR assay for characterization of New World Leishmania
complexes.
AB - We have developed a PCR assay for one-step differentiation of the three complexes
of New World Leishmania (Leishmania braziliensis, Leishmania mexicana, and
Leishmania donovani). This multiplex assay is targeted to the spliced leader RNA
(mini-exon) gene repeats of these organisms and can detect all three complexes
simultaneously, generating differently sized products for each complex. The assay
is specific to the Leishmania genus and does not recognize related kinetoplastid
protozoa, such as Trypanosoma cruzi, Trypanosoma brucei, and Crithidia
fasciculata. It correctly identified Leishmania species with a broad geographic
distribution in Central and South America. The sensitivity of the PCR
amplification ranged from 1 fg to 10 pg of DNA (0.01 to 100 parasites), depending
on the complex detected. Crude extracts of cultured parasites, prepared simply by
boiling diluted cultures, served as excellent templates for amplification. Crude
preparations of clinical material were also tested. The assay detected L.
braziliensis in dermal scrapings from cutaneous leishmanial lesions, Leishmania
chagasi in dermal scrapings of atypical cutaneous leishmaniasis, and L. mexicana
from lesion aspirates from infected hamsters. We have minimized the material
requirements and maximized the simplicity, rapidity, and informative content of
this assay to render it suitable for use in laboratories in countries where
leishmaniasis is endemic. This assay should be useful for rapid in-country
identification of Leishmania parasites, particularly where different Leishmania
complexes are found in the same geographical area.
PMID- 9650951
TI - Novel method for processing respiratory specimens for detection of mycobacteria
by using C18-carboxypropylbetaine: blinded study.
AB - A novel method for processing respiratory specimens to improve culture and acid
fast staining of mycobacteria is introduced. This new method utilized N,N
dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical
Abstract Service no. 78195-27-4), also known as C18-carboxypropylbetaine (CB-18).
In a blinded, five-center study, CB-18-based processing was compared to the
standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory
specimens were tested. Individual specimens were split approximately equally; the
host institutions processed half of each specimen by the NALC/NaOH method, while
the other half was processed with CB-18 at Quest Diagnostics--Baltimore. A total
of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement
of the primary decontamination agent with CB-18 caused changes in all diagnostic
parameters. Aggregate culture sensitivity improved by approximately 43% (P <
0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The
sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P
< 0.01) when specimens were processed with CB-18. The average times to a positive
result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on
solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate
in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing.
There were also unusual reductions in liquid culture sensitivity and smear
specificity among CB-18-processed specimens. The characteristics of the latter
parameters suggested that refinement of the CB-18 processing method should allow
further improvements in culture sensitivity. This study showed that the CB-18
method has the potential to improve both smear and culture detection for these
important human pathogens.
PMID- 9650952
TI - Processing respiratory specimens with C18-carboxypropylbetaine: development of a
sediment resuspension buffer that contains lytic enzymes to reduce the
contamination rate and lecithin to alleviate toxicity.
AB - The C18-carboxypropylbetaine (CB-18) procedure for processing respiratory
specimens for the detection of mycobacteria was shown to provide significant
increases in sensitivity by smear and culture. However, the procedure also
produced increased contamination, a loss in liquid culture sensitivity, and a
reduction in smear specificity. Because of these observations, the toxicity of CB
18 and the nature of the contamination were characterized. Preincubation in 1 mM
CB-18 impacted viability in a time-dependent fashion, but the magnitude of the
loss was species and isolate dependent. Mycobacterium tuberculosis isolates were
the most susceptible, losing 20 to 30% of the CFU within 30 min and 30 to 60%
after 3 h, whereas Mycobacterium avium and Mycobacterium fortuitum isolates were
unaffected by CB-18. In liquid culture, when the concentration of CB-18 exceeded
5 microg/ml, there was an impact on growth characteristics for the most
susceptible M. tuberculosis isolate. In contrast, M. fortuitum isolates were able
to grow in 100 microg of CB-18 per ml. In liquid culture, the deleterious effects
of CB-18 were enhanced in the presence of antibiotics, whereas growth on solid
media was not similarly affected. Supplementation of the resuspension buffer with
0.15% lecithin alleviated toxicity. Initial attempts to modify the CB-18
procedure to control contamination incorporated acids or alkalis; however, losses
in culture sensitivity occurred. Studies to identify these contaminants led to
the development of a sediment resuspension buffer that contained lytic enzymes to
combat contamination and lecithin to alleviate toxicity. This formulation
included lysozyme, zymolyase, and Cytophaga and Trichoderma extracts and was seen
to reduce contamination to acceptable levels (<5%).
PMID- 9650953
TI - Recombinant hepatitis A virus antigen: improved production and utility in
diagnostic immunoassays.
AB - Hepatitis A virus (HAV) immunoassays use cell culture-derived HAV antigen to
detect HAV-specific antibodies. The current method of production of HAV antigen
in tissue culture is time-consuming and expensive. We previously expressed the
HAV open reading frame in recombinant vaccinia viruses (rV-ORF). The recombinant
HAV polyprotein was accurately processed and was assembled into subviral
particles. These particles were bound by HAV-neutralizing antibodies and were
able to elicit antibodies which were detected by commercial immunoassays. The
present investigation compared the production of HAV antigen by standard tissue
culture methods to the production of HAV antigen with the recombinant vaccinia
virus system. In addition, HAV and rV-ORF antigens were assessed for their
utility in diagnostic immunoassays. Serum or plasma samples from HAV antibody
positive and antibody-negative individuals were evaluated by immunoassay that
used either HAV or rV-ORF antigen. All samples (86 of 86) in which HAV antibody
was detected by a commercial enzyme-linked immunosorbent assay (ELISA) also
tested positive by the recombinant antigen-based immunoassay (VacRIA). Similarly,
all samples (50 of 50) that were HAV antibody negative also tested negative by
the VacRIA. The lower limit of detection of HAV antibody was similar among
immunoassays with either HAV or rV-ORF antigen. Thus, in the population studied,
the sensitivity and specificity of the VacRIA were equivalent to those of the
commercial ELISA. Since production of recombinant antigen is faster and less
expensive than production of traditional HAV antigen, the development of
diagnostic HAV antibody tests with recombinant HAV antigen appears warranted.
PMID- 9650954
TI - Characterization of serologically nontypeable Actinobacillus
actinomycetemcomitans isolates.
AB - Our previous studies have shown that Actinobacillus actinomycetemcomitans
isolates of a given arbitrarily primed PCR (AP-PCR) genotype belong to the same
serotype (of serotypes a through e). In the present study we investigated whether
the AP-PCR genotypes of nonserotypeable A. actinomycetemcomitans isolates match
those of the serotypeable isolates. The isolates were additionally characterized
by restriction analysis of the apaH PCR amplification products. The material
included 75 nonserotypeable and 18 serotypeable A. actinomycetemcomitans isolates
from 34 epidemiologically unrelated subjects. The serotypeable isolates were
obtained from subjects who also harbored nonserotypeable isolates. Eight AP-PCR
genotypes were distinguished among the isolates; six genotypes matched those
detected in our previous studies, whereas two genotypes were new.
Intraindividually, the A. actinomycetemcomitans isolates produced identical AP
PCR banding patterns, regardless of whether they were serotypeable or
nonserotypeable, in 22 of 23 subjects participating with multiple isolates. AP
PCR genotype 3, corresponding to serotype c, was by far the most common among the
nonserotypeable isolates (62% of subjects). Results obtained with the apaH
restriction analysis confirmed the results obtained with AP-PCR for 31 of the 34
subjects. The results suggest that nonserotypeable A. actinomycetemcomitans
isolates originate from serotypeable isolates, especially from serotype c
isolates, and the likelihood of the existence of additional serotypes is small.
PMID- 9650955
TI - Comparison of Roche Cobas Amplicor Mycobacterium tuberculosis assay with in-house
PCR and culture for detection of M. tuberculosis.
AB - The new Roche Cobas Amplicor Mycobacterium tuberculosis assay, which is a
semiautomated version of the manually performed Roche Amplicor M. tuberculosis
test, was compared to culture and an IS6110-based in-house PCR protocol. A total
of 1,681 specimens from 833 patients, including specimen types other than sputum,
were tested in parallel by both the in-house PCR and the Cobas Amplicor M.
tuberculosis assay. After we resolved discrepant PCR results, the sensitivity,
specificity, and positive and negative predictive values for the Cobas Amplicor
M. tuberculosis assay were 66.33, 99.71, 94.36, and 97.66%, respectively. The
corresponding values for the in-house PCR were 91.08, 99.85, 97.87, and 99.37%,
respectively. For culture- and smear-positive specimens, the sensitivity of the
Cobas Amplicor M. tuberculosis test was 96.42% (in-house PCR, 100%). If only
smear-negative sputum specimens were considered, the Cobas Amplicor M.
tuberculosis assay exhibited a sensitivity of 45.45% (in-house PCR, 63.63%)
relative to that of culture. With a modified protocol for DNA extraction (washing
of samples plus ultrasonication), both PCR methods performed better with gastric
aspirates than with sputum samples (sensitivity of the Cobas Amplicor M.
tuberculosis assay with smear-negative gastric aspirates, 70.00%; sensitivity of
in-house PCR, 90.00%). With dithiothreitol being used for liquefaction of
specimens in this study, the Cobas Amplicor M. tuberculosis assay exhibited an
inhibition rate of 9.16%. In our view, the new Cobas Amplicor M. tuberculosis
test (i) is well suited for typing of smear-positive specimens, (ii) may also be
applied to gastric aspirates and other types of specimens if DNA extraction
methods are modified appropriately, and (iii) exhibits a sensitivity with smear
negative sputum specimens which makes it recommendable that a minimum of three
samples from the same patient be tested.
PMID- 9650957
TI - Identification of a granulocytic Ehrlichia strain isolated from a horse in
Switzerland and comparison with other rickettsiae of the Ehrlichia phagocytophila
genogroup.
AB - This case report describes a 12-year-old Arabian mare with granulocytic
ehrlichiosis. Clinical signs included fever, apathy, anorexia, icterus, limb
edema, and reluctance to move. Examination of buffy coat smears revealed
Ehrlichia organisms in neutrophils and eosinophils. A band of 1,428 bp was
amplified from DNA of leukocytes via nested PCR and was identified as part of the
Ehrlichia 16S rRNA gene. It differed from the gene sequences of Ehrlichia
phagocytophila and E. equi at two and three positions, respectively.
Interestingly, the nucleotide sequence of the 16S rRNA was 100% identical to that
of the agent of human granulocytic ehrlichiosis.
PMID- 9650956
TI - Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme
immunoassay.
AB - Japanese encephalitis (JE) occurs in rural settings in southern and eastern Asia,
where diagnostic facilities are limited. For the diagnosis of JE virus (JEV)
infection, we developed a nitrocellulose membrane-based immunoglobulin M (IgM)
capture dot enzyme immunoassay (MAC DOT) that is rapid, simple to use, requires
no specialized equipment, and can distinguish JEV from dengue infection. In a
prospective field study in southern Vietnam, 155 cerebrospinal fluid (CSF) and
341 serum samples were collected from 111 children and 83 adults with suspected
encephalitis. The JEV MAC DOT, performed on site, was scored visually from
negative to strongly positive by two observers, and the results were compared
subsequently with those of the standard IgM capture enzyme-linked immunosorbent
assay. For the 179 patients with adequate specimens, the MAC DOT correctly
identified 59 of 60 JEV-positive patients and 118 of 119 JEV-negative patients
(sensitivity [95% confidence intervals], 98.3% [92.1 to 99.91%]; specificity,
99.2% [95.9 to 100.0%]; positive predictive value, 0.98; negative predictive
value, 0.99). The MAC DOT also correctly identified three patients with dengue
encephalopathy. Admission specimens were positive for 73% of JE patients.
Interobserver agreement for MAC DOT diagnosis was excellent (kappa = 0.94). The
JEV MAC DOT is a simple and reliable rapid diagnostic test for JE in rural
hospitals.
PMID- 9650958
TI - Distribution of Staphylococcus species among human clinical specimens and emended
description of Staphylococcus caprae.
AB - By DNA-DNA hybridization on microplates, we identified 1,230 strains of
staphylococci from human clinical specimens and determined the distribution of
species. The 10 Staphylococcus species isolated most often were S. epidermidis
(31.3%), S. aureus (23.3%), S. haemolyticus (12.2%), S. caprae (10.7%), S.
simulans (4.4%), S. hominis (4.0%), S. capitis (3.9%), S. saprophyticus (3.6%),
S. warneri (2.2%), and S. lugdunensis (1.3%). From these results, we realized
that S. caprae strains were widely distributed in human clinical specimens. The
description in Bergey's Manual of Systematic Bacteriology indicates that no
strains of S. caprae produce acid from fructose and mannitol, but all our S.
caprae strains produced acid from fructose and mannitol. Consequently, many
strains of S. caprae isolated from human clinical specimens have been
misidentified as S. haemolyticus or S. hominis by conventional biochemical tests.
In this paper, we propose an emended description of S. caprae.
PMID- 9650959
TI - Microtiter assay for detecting Campylobacter spp. and Helicobacter pylori with
surface gangliosides which bind cholera toxin.
AB - Campylobacter jejuni with Gm1 ganglioside in the core of its lipopolysaccharide
has been associated with Guillain-Barre syndrome. Since this epitope may be of
considerable pathophysiologic importance and since this ganglioside binds cholera
toxin, a rapid screening assay to detect bacteria that bind cholera toxin as an
indication of Gm1 on their surfaces was developed. In the assay, bacterial lawns
were grown on agar plates, harvested with phosphate-buffered saline, boiled, and
incubated with a standard concentration of cholera B subunit. Preparations from
strains with Gm1 were observed to inhibit the binding of cholera B subunit to Gm1
in a microtiter enzyme-linked immunosorbent assay. By using this assay with two
groups of strains, 37 positive strains were detected among the 197 tested.
Species with positive isolates included C. jejuni, Campylobacter coli, and
Helicobacter pylori. The assay is capable of testing large numbers of isolates
and should prove useful in future clinical and epidemiological studies of
bacteria with this epitope.
PMID- 9650960
TI - The L1 major capsid protein of human papillomavirus type 16 variants affects
yield of virus-like particles produced in an insect cell expression system.
AB - The L1 major capsid proteins of six human papillomavirus type 16 (HPV-16) strains
were expressed in insect cells by using recombinant baculoviruses. Virus-like
particles (VLPs) which appeared similar to empty virions were identified by
electron microscopy for all HPV strains investigated. However, the yield of VLPs
produced varied in a range from 1 to 79 depending on the HPV-16 strain. The L1
proteins of these strains differed by up to 15 amino acids from the L1 protein of
the prototype HPV-16 strain. Mutations in the amino acid region from residues 83
to 97 seemed to affect the level of expression of the L1 protein. These results
are important when considering the development of HPV vaccines and serological
tests. They indicate that strains inducing high levels of VLP production must be
selected for the development of vaccines. Moreover, the L1 proteins of all
strains investigated were able to bind with DNA. We also investigated the
seroreactivities of VLPs derived from three different HPV-16 strains from
Algeria, Senegal, and the Philippines by testing sera from women from 11
countries in immunoglobulin G-specific enzyme-linked immunosorbent assays. We
observed a strong correlation between the reactivities of the three different VLP
variants, independent of the geographical origin of the sera investigated. These
results indicate that the three strains investigated are serologically cross
reactive despite the fact that their L1 proteins differ in 14 amino acids and
suggest that VLPs derived from only one HPV-16 strain could be sufficient for the
development of an HPV-16 vaccine and anti-HPV-16 tests.
PMID- 9650961
TI - Direct susceptibility testing with positive BacT/Alert blood cultures by using
MicroScan overnight and rapid panels.
AB - Studies were conducted on a method of direct inoculation of MicroScan dried
overnight and of rapid panels with positive aerobic blood cultures obtained from
the BacT/Alert to determine antimicrobial susceptibilities. Inocula were limited
to specimens that appeared unimicrobic on Gram stain. Results were compared to
those obtained from panels inoculated following subculture. For 133 gram-negative
bacilli, there were 94.7 and 93.5% categorical agreements between direct and
standard methods for all drugs tested with overnight and rapid panels,
respectively. For 104 gram-positive cocci, there were 93.2 and 93.1% categorical
agreements for overnight and rapid panels, respectively. The major error (false
resistance) rate for gram negatives was 1.4% for overnight versus 0.7% for rapid
panels. The very major error (false susceptibility) rate was 2.7% for overnight
versus 8.1% for rapid panels. The total error rates were 1.6% for overnight
panels and 1.5% for rapid panels. The major error rates for gram-positive direct
susceptibility tests were 2.6% for overnight and 2.5% for rapid panels. The very
major error rates were 8.8 and 7.2% for overnight and rapid panels, respectively.
Total error rates were 3.6% for overnight and rapid gram-positive panels. These
findings suggest that susceptibility results obtained from directly inoculated
gram-negative overnight panels have the greatest correlation to those obtained by
standard methods. When discrepant results occur with direct-susceptibility
testing, they are more likely to show false susceptibility than false resistance.
PMID- 9650962
TI - Utility of random amplified polymorphic DNA PCR and TaqMan automated detection in
molecular identification of Aspergillus fumigatus.
AB - We developed a method for the identification of Aspergillus fumigatus fungal
isolates by using random amplified polymorphic DNA (RAPD) PCR (RAPD-PCR) cloning
and the TaqMan LS50B fluorogenic detection system (Perkin-Elmer Corp., Applied
Biosystems, Foster City, Calif.). DNA from seven clinically important Aspergillus
species was screened by RAPD-PCR to identify section- or species-specific
amplicons. With the OPZ19 RAPD primer a 1,264-bp product was amplified from all
A. fumigatus strains initially examined but not from other species. A partial DNA
sequence of this product was used to design a specific primer pair, which
generated a single 864-bp fragment with DNA from 90 of 100 A. fumigatus isolates
when a "touchdown" (65-->55 degrees C) annealing protocol was used. The TaqMan
system, a fluorogenic assay which uses the 5'-->3' endonuclease activity of Taq
DNA polymerase, detected this 864-bp product with DNA from 89 of these 90 A.
fumigatus strains; 1 DNA sample generated an indeterminate result. With DNA from
three morphologically typical A. fumigatus isolates, six white ("albino") A.
fumigatus isolates, and five of six Neosartorya species (non-A. fumigatus members
of the section Fumigati), the 864-bp product was amplified differentially at an
annealing temperature of 56 degrees C but not with the touchdown annealing
format. No amplicon was detected with DNA from 56 isolates of heterologous
Aspergillus, Penicillium, and Paecilomyces species or from Neosartorya
fennelliae; TaqMan assay results were either negative (51 isolates) or
indeterminate (5 isolates) for all isolates. This RAPD-PCR and TaqMan assay
offers promise as a nucleic acid-based system that can be used for the
identification of filamentous fungal isolates and that requires no
postamplification sample manipulations.
PMID- 9650963
TI - Q fever in the Greek island of Crete: detection, isolation, and molecular
identification of eight strains of Coxiella burnetii from clinical samples.
AB - Over a period of 6 years (1989 to 1995), serum samples from 3,300 patients
suspected to be infected by Coxiella burnetii were assayed for the presence of
antibodies against antigen phase II of the microorganism by the indirect
immunofluorescence antibody technique (IFAT). One hundred fifty-two cases were
recorded, and blood samples from 17 patients were cultured for the isolation of
the pathogen. By a centrifugation shell vial technique, eight strains were
isolated from patients suffering from acute Q fever. The microorganism was
detected in the cultures by IFAT, by Gimenez staining, and by the cytopathogenic
effect on Vero and human embryonic lung (HEL) cells. PCR followed by restriction
fragment length polymorphism analysis was used to confirm the diagnosis and
identify the Coxiella burnetii strains within the cell cultures as well as to
compare them with reference strains. In order to avoid time-consuming cultures,
to achieve direct detection of Coxiella burnetii in clinical samples (blood,
buffy coat, etc.), and to increase the specificity and sensitivity of the
detection, nested PCR was performed. The first step of DNA extraction was
performed with the QIAamp blood kit 250. For the second step of the PCR assays,
the conditions of temperature and times of recycling were properly modified, and
the microorganism was detected within 4 h. Our study demonstrates that Q fever is
an endemic disease in Crete and that the diagnosis of Coxiella burnetii infection
can be rapidly achieved by the detection of the microorganism in buffy coat
samples by nested PCR. Although the presenting symptoms of the disease in this
study differed from those in other studies, the Cretan strains do not differ
genotypically from the reference strains (Nine Mile and Q212).
PMID- 9650964
TI - Diagnostic use of PCR for detection of Pneumocystis carinii in oral wash samples.
AB - There is a need to develop noninvasive methods for the diagnosis of Pneumocystis
carinii pneumonia in patients unable to undergo bronchoscopy or induction sputum.
Oral wash specimens are easily obtained, and P. carinii nucleic acid can be
amplified and demonstrated by PCR. In routine clinical use, easy sample
processing and single-round PCR are needed to ensure rapid analysis and to reduce
the risk of contamination. We developed a single-round Touchdown PCR (TD-PCR)
protocol with the ability to detect PCR inhibition in the specimen. The TD-PCR
was evaluated in a routine diagnostic laboratory and was compared to a previously
described PCR protocol (mitochondrial RNA) run in a research laboratory. Both PCR
methods amplified a sequence of the mitochondrial rRNA gene of P. carinii. Paired
bronchoalveolar lavage (BAL) and oral wash specimens from 76 consecutive human
immunodeficiency virus type 1-infected persons undergoing a diagnostic
bronchoscopy were included. The TD-PCR procedure was quicker than the
mitochondrial PCR procedure (<24 versus 48 h) and, compared to microscopy, had
sensitivity, specificity, and positive and negative predictive values of 89, 94,
93, and 91%, respectively, for oral wash specimens and 100, 91, 90, and 100%,
respectively, for BAL specimens. Our results suggest that oral wash specimens are
a potential noninvasive method to obtain a diagnostic specimen during P. carinii
pneumonia infection and that it can be applied in a routine diagnostic
laboratory.
PMID- 9650965
TI - Assessment of spontaneous fluctuations of viral load in untreated patients with
chronic hepatitis C by two standardized quantitation methods: branched DNA and
Amplicor Monitor.
AB - Quantitation of hepatitis C virus (HCV) RNA in serum has been used to predict and
monitor the efficacy of interferon therapy in chronic HCV infection. We
prospectively studied the fluctuation of viremia by a longitudinal follow-up of
HCV RNA levels for 2 months in six untreated patients. Spontaneous fluctuations
of HCV RNA ranged from 2.8- to 5.7-fold with branched DNA assay and from 2.9- to
5.6-fold with Monitor. These large spontaneous fluctuations (up to 0.75 log),
observed daily, weekly, and monthly, raise doubt about the clinical value of a
single assessment of pretherapeutic viremia.
PMID- 9650966
TI - Survey of incidence of Clostridium difficile infection in Canadian hospitals and
diagnostic approaches.
AB - A questionnaire relating to Clostridium difficile disease incidence and
diagnostic practices was sent to 380 Canadian hospitals (all with > 50 beds). The
national questionnaire response rate was 63%. In-house testing was performed in
17.6, 61.5, and 74.2% of the hospitals with < 300, 300 to 500, and > 500 beds,
respectively. The average test positivity rates were 17.2, 15.3, and 13.2% for
hospitals with < 300, 300 to 500, and > 500 beds, respectively. The average
disease incidences were 23.5, 30.8, and 40.3 cases per 100,000 patient days in
the hospitals with < 300, 300 to 500, and > 500 beds, respectively. In the 81
hospitals where in-house testing was performed, cytotoxin testing utilizing
tissue culture was most common (44.4%), followed by enzyme-linked immunosorbent
assay (38.3%), culture for toxigenic C. difficile (32.1%), and latex
agglutination (13.6%). The clinical criteria for C. difficile testing were
variable, with 85% of hospitals indicating that a test was done automatically if
ordered by a doctor. Our results show that C. difficile-associated diarrhea is a
major problem in hospitals with > or = 200 beds. Despite a lower disease
incidence in smaller hospitals, there was a higher diagnostic test positivity
rate. This may reflect the preference of smaller hospitals for culture and latex
agglutination tests.
PMID- 9650967
TI - Molecular diagnosis of human rhinovirus infections: comparison with virus
isolation.
AB - To compare the sensitivity and specificity of RT-PCR with that of virus isolation
in the detection of human rhinoviruses, we tested nasopharyngeal aspirates from
200 patients on the 1st and 7th days after the onset of the common cold. An assay
utilizing a short amplicon in the conserved 5' noncoding region was found highly
sensitive. Of 192 positive samples altogether, 65 were found positive by RT-PCR
only, 6 were positive by isolation exclusively, and 121 gave positive results in
both tests.
PMID- 9650968
TI - Low-level viremia and intracellular expression of hepatitis B surface antigen
(HBsAg) in HBsAg carriers with concurrent hepatitis C virus infection.
AB - Assays of hepatitis B virus (HBV) replication and antigen expression in HBV
surface antigen (HBsAg) carriers with concurrent hepatitis C or D virus (HCV or
HDV) infection revealed that HCV and HDV can suppress HBV replication but that
HCV also substantially suppresses HBV surface protein expression. HBsAg carriers
with concurrent HCV infection thus have low-level viremia and intracellular
HBsAg.
PMID- 9650969
TI - Coryneform bacteria in throat cultures of healthy individuals.
AB - Throat swabs from 113 healthy individuals from Hamburg, Germany, and Zurich,
Switzerland, were investigated for coryneform bacteria with nonselective and
selective media. Ninety specimens contained 123 strains. Surprisingly, 76% of
them were strains of Corynebacterium durum (47%) and Rothia dentocariosa (29%).
Only two were strains of Corynebacterium pseudodiphtheriticum, and none were
strains of C. striatum, C. amycolatum, or C. diphtheriae.
PMID- 9650970
TI - Clinical importance of identifying coagulase-negative staphylococci isolated from
blood cultures: evaluation of MicroScan Rapid and Dried Overnight Gram-Positive
panels versus a conventional reference method.
AB - We evaluated the clinical usefulness of species identification of blood isolates
of coagulase-negative staphylococci as a predictor of the clinical significance
of the isolates. In addition, we compared results of species identification
obtained with MicroScan Rapid Gram-Positive Identification panels and Dried
Overnight (Conventional) Gram-Positive Identification panels with those obtained
by a tube reference method. Two hundred eighty-five blood isolates were tested,
including 92 judged to represent true bacteremia and 193 judged to represent
contamination. The most common species detected were Staphylococcus epidermidis,
Staphylococcus hominis, and Staphylococcus haemolyticus. These three species
accounted for nearly 98% of the clinically significant isolates and 89% of the
contaminants. The isolation of other species almost always represented
contamination. However, identification of the three most common species did not
help distinguish pathogens from contaminants. Both the Rapid and the Dried
Overnight Gram-Positive panels identified S. epidermidis strains accurately, but
the panels performed less well for the other species. Analysis revealed that S.
hominis was frequently misidentified due to the presence of a previously unknown
subspecies. Based on the initial results, revised investigational Dried Overnight
Gram-Positive Identification panels (CPID-2) were prepared and tested. The CPID-2
panels identified 85 to 95% of S. epidermidis strains, 76 to 86% of S. hominis
strains, and 88 to 92% of S. haemolyticus strains with high probability (>85%)
and, overall, represented a significant improvement over the other panels for
identification of these staphylococcal species.
PMID- 9650971
TI - Simple, inexpensive, reliable method for differentiation of Candida dubliniensis
from Candida albicans.
AB - Candida dubliniensis is a recently described pathogenic species which shares many
phenotypic features with Candida albicans, including the ability to form germ
tubes and chlamydospores. These similarities have caused significant problems in
the identification of C. dubliniensis by the average clinical mycology
laboratory. To facilitate the differentiation of these species, we investigated
the growth of 120 isolates of C. dubliniensis and 98 C. albicans isolates at 42
and 45 degrees C on Emmons' modified Sabouraud glucose agar (SGA) and 10 isolates
of each species in yeast-peptone-dextrose broth. None of the C. dubliniensis
isolates grew on the agar or in the broth medium at 45 degrees C, while 11
isolates were capable of growing on SGA at 42 degrees C. In contrast, all of the
C. albicans isolates but one grew at 45 degrees C on or in either medium. These
reproducible results clearly demonstrate that the incubation of isolates
suspected to be C. dubliniensis or C. albicans at 45 degrees C provides a simple,
reliable, and inexpensive method for the differentiation of the two species.
PMID- 9650972
TI - Quantification of human immunodeficiency virus type 1 RNA levels in plasma by
using small-volume-format branched-DNA assays.
AB - We have developed small-volume (50 or 250 microl)-format branched-DNA assays for
human immunodeficiency virus type 1 (HIV-1) RNA for use with specimens in which
the volume is limited and/or a high viral load is anticipated. These formats
exhibited good correlation with the standard 1-ml format; high specificity,
reproducibility, and linearity; and no significant difference in the
quantification of HIV-1 subtypes.
PMID- 9650973
TI - Clonal nature of enterotoxigenic Escherichia coli serotype O6:H16 revealed by
randomly amplified polymorphic DNA analysis.
AB - The genetic relatedness among 29 enterotoxigenic Escherichia coli strains of
serotype O6:H16 was investigated by randomly amplified polymorphic DNA (RAPD)
analysis. The strains were isolated in different parts of the world, displayed
CS1-CS3 or CS2-CS3 profiles, and expressed heat-labile toxin (LT) and heat-stable
toxin; a single strain expressed only LT. Ten RAPD types were distinguished and
showed significant similarity, having on average 82% of the amplified bands in
common. These results indicated that, irrespective of the different geographical
origin or virulence factors, these strains belonged to a widespread clonal group.
PMID- 9650974
TI - Evidence of Toscana virus variants circulating in Tuscany, Italy, during the
summers of 1995 to 1997.
AB - The Toscana virus can cause neurological infection in adults. This study of 112
cases of acute meningitis which occurred during the summers of 1995, 1996, and
1997 demonstrated the presence of viral RNA in the cerebrospinal fluid of 56
patients. Their sequence analysis shows four variants of the Toscana virus.
PMID- 9650975
TI - Genetic analysis of multiple vancomycin-resistant Enterococcus isolates obtained
serially from two long-term-care patients.
AB - Fifty-eight vancomycin-resistant enterococcal isolates were obtained from two
patients over 9 weeks. Numerous pulsed-field gel electrophoresis fingerprinting
types were isolated from each patient. By PCR, all isolates were vanA+. However,
many isolates from patient B were found to lack vanA by hybridization. Our
results demonstrate the importance of examining multiple isolates, especially
from patients who are at high risk of infection.
PMID- 9650976
TI - Replication of bovine herpesvirus type 4 in human cells in vitro.
AB - A reference strain (Movar 33/63) of bovine herpesvirus type 4 (BHV-4) was
inoculated into 14 different human cell lines and five primary cell cultures
representing various human tissues. BHV-4 replicated in two embryonic lung cell
lines, MRC-5 and Wistar-38, and in a giant-cell glioblastoma cell culture.
Cytopathic effect and intranuclear inclusion bodies were observed in these cells.
PCR detected a 10,000-times-higher level of BHV-4 DNA. Titration of the
supernatant indicated a 100-fold increase of infectious particles. Since this is
the first bovine (human herpesvirus 8 and Epstein-Barr virus related) herpesvirus
which replicates on human cells in vitro, the danger of possible human BHV-4
infection should not be ignored.
PMID- 9650977
TI - Use of fluorescent-antibody staining of cytocentrifuge-prepared smears in
combination with cell culture for direct detection of respiratory viruses.
AB - Over a 3-year period, 1,003 respiratory samples were collected and examined for
selected respiratory viruses with cytocentrifuged prepared smears stained with
fluorescently labeled antibodies (IFA) in conjunction with cell culture. IFA
results were compared with results obtained by cell culture. Viruses were
isolated or detected by direct means in 401 samples. Agreement between culture
and IFA was 90%.
PMID- 9650978
TI - Sudden increase in isolation of group B streptococci, serotype V, is not due to
emergence of a new pulsed-field gel electrophoresis type.
AB - Until recently, group B streptococcus, serotype V (GBS-V), was an infrequent
cause of disease. It is now recognized as a significant cause of infections in
both children and adults. To determine if this increase was due to the recent
introduction and spread of a single clone of GBS-V, we analyzed, by pulsed-field
gel electrophoresis (PFGE), the SmaI chromosomal DNA digests of 45 bacteria: 41
isolated from human infections between 1986 and 1996 in the United States, 2 from
human infections in Argentina, and 2 from naturally infected mice. Seventeen
patterns were found and arbitrarily designated patterns A to Q. Pattern N
constituted 24 (53%) of the isolates and was found in all of the years tested and
from all surveillance areas, as well as in both isolates from Argentina, and was
very similar to the GBS-V isolated from a mouse. Pattern P was found in three
isolates, pattern F was found in two, and the remaining patterns were found in
one isolate each. We concluded that the majority of isolates of GBS-V are of one
PFGE subtype and that this subtype was predominate before the increase in disease
caused by GBS-V and that GBS-V disease is caused by several different subtypes.
PMID- 9650979
TI - Effects of various handling and storage conditions on stability of Treponema
pallidum DNA in cerebrospinal fluid.
AB - Treponema pallidum DNA from even small numbers of organisms was detectable in
cerebrospinal fluid (CSF) stored at room temperature or at 4 degrees C for
several hours and in CSF subjected to three freeze-thaw cycles. These results
suggest that negative PCR results for T. pallidum from patients diagnosed with T.
pallidum invasion of the central nervous system are probably not due to the loss
of target DNA prior to testing.
PMID- 9650980
TI - Comparison of sample preparation methods for detection of Legionella pneumophila
in culture-positive bronchoalveolar lavage fluids by PCR.
AB - A prospective study was conducted on 25 Legionella pneumophila culture-positive
and 98 culture-negative bronchoalveolar lavage fluid samples to compare two DNA
preparation methods: a rapid modified Chelex-based protocol and a proteinase K
method. PCR was found to be more sensitive with the Chelex-based method (P =
0.03). N difference was found concerning the inhibition rate.
PMID- 9650981
TI - Chromosomal rearrangements in Salmonella enterica serotype typhi affecting
molecular typing in outbreak investigations.
AB - Salmonella enterica serotype Typhi strains belonging to eight different outbreaks
of typhoid fever that occurred in Spain between 1989 and 1994 were analyzed by
ribotyping and pulsed-field gel electrophoresis. For three outbreaks, two
different patterns were detected for each outbreak. The partial digestion
analysis by the intron-encoded endonuclease I-CeuI of the two different strains
from each outbreak provided an excellent tool for examining the organization of
the genomes of epidemiologically related strains. S. enterica serotype Typhi
seems to be more susceptible than other serotypes to genetic rearrangements
produced by homologous recombinations between rrn operons; these rearrangements
do not substantially alter the stability or survival of the bacterium. We
conclude that genetic rearrangements can occur during the emergence of an
outbreak.
PMID- 9650982
TI - Borna disease in a dog with lethal meningoencephalitis.
AB - A dog was euthanatized because of progressive neurological signs. Histologically,
a nonsuppurative meningoencephalitis was found. By immunohistochemistry, in situ
hybridization, and nested PCR procedures, Borna disease virus (BDV) antigen and
BDV-specific RNA were demonstrated in brain tissues of the dog. The nucleotide
sequence of the PCR product showed 94 to 98% homology to published BDV sequences.
This is the first description of Borna disease in a dog.
PMID- 9650983
TI - Experimental transmission of Ehrlichia equi to horses through naturally infected
ticks (Ixodes pacificus) from Northern California.
AB - We report the experimental transmission of Ehrlichia equi from naturally infected
Ixodes pacificus ticks to horses. Three weeks after exposure to ticks, two of
three horses developed clinical signs compatible with E. equi infection, while
one horse remained asymptomatic. 16S rRNA gene PCR of blood leukocyte lysates was
positive for all horses at various time points; two horses seroconverted. The 16S
rRNA gene sequences amplified from tick-exposed horses showed more than 99%
homology to corresponding fragments of the 16S rRNA genes of E. equi, Ehrlichia
phagocytophila, and the human granulocytic ehrlichiosis agent.
PMID- 9650984
TI - Isolation and characterization of sorbitol-fermenting Shiga toxin (Verocytotoxin)
producing Escherichia coli O157:H- strains in the Czech Republic.
AB - Two sorbitol-fermenting (SF) Shiga toxin-producing Escherichia coli (STEC) O157:H
strains were isolated from patients with hemolytic-uremic syndrome in the Czech
Republic in 1995. Their phenotypic and genotypic characteristics and genomic DNA
fingerprints were identical or closely related to those of SF STEC O157:H-
strains isolated in Germany in 1988 to 1997. This indicates that the Czech
isolates belong to the SF STEC O157 clone which is widespread in Germany. It is
the first finding of the clone outside Germany.
PMID- 9650985
TI - Bacillus thuringiensis subsp. konkukian (serotype H34) superinfection: case
report and experimental evidence of pathogenicity in immunosuppressed mice.
AB - We present a case of severe war wounds infected by Bacillus thuringiensis
serotype H34 and describe the experimental protocol used to demonstrate its
ability to infect mice after cutaneous inoculation. This case is interesting
because B. thuringiensis is considered to be a contaminant in laboratories and
receives inadequate attention.
PMID- 9650986
TI - Therapeutic effect of doxycycline in experimental subclinical canine monocytic
ehrlichiosis: evaluation of a 6-week course.
AB - The efficacy of doxycycline treatment (10 mg/kg of body weight every 24 h for 42
days) in eliminating Ehrlichia canis from four subclinically infected dogs was
evaluated. One dog remained PCR positive, suggesting that 6 weeks of doxycycline
treatment may not be sufficient to clear E. canis parasites from all
subclinically infected dogs. Serology (indirect immunofluorescent antibody assay)
was shown to be unreliable in assessing recovery from the carrier state, as anti
E. canis antibodies persisted after elimination of the parasite. Our findings
suggest that an increase in the platelet count may be an important indicator for
dogs that recover from subclinical ehrlichiosis.
PMID- 9650987
TI - Line probe assay for detection of human immunodeficiency virus type 1 mutations
conferring resistance to nucleoside inhibitors of reverse transcriptase:
comparison with sequence analysis.
AB - We compared the line probe assay (LiPA) to sequence analysis for the detection of
mutations conferring resistance to nucleoside inhibitors of human
immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Plasma samples
from 40 patients who had received zidovudine, dideoxyinosine, and
dideoxycytosine, alone or in combination, and who were enrolled in the ALTIS 2
clinical trial (lamivudine [3TC] plus stavudine) were tested at enrollment and at
week 24. RT PCR products from plasma were used for LiPA, and DNA was used for
sequence analysis. LiPA gave uninterpretable results for 8.5% of the analyzed
codons corresponding to 63 samples, mainly for codons 41, 69, and 70. Several
minor discrepancies between the two methods occurred, mainly due to the ability
of LiPA to detect mixed populations while sequence analyses detect a single
homogeneous population. LiPA is suitable for detecting mixed populations and easy
to implement in clinical laboratories and might be useful for epidemiological
surveys of primary HIV-1 resistance.
PMID- 9650988
TI - Facklamia ignava sp. nov., isolated from human clinical specimens.
AB - Two strains of a hitherto-undescribed gram-positive, catalase-negative coccus
isolated from human sources were characterized by phenotypic and molecular
taxonomic methods. Comparative 16S rRNA gene sequencing studies demonstrated that
the unknown strains are genealogically identical and constitute a new line close
to, but distinct from, Facklamia hominis. The unknown bacterium was readily
distinguished from F. hominis by biochemical tests and electrophoretic analysis
of whole-cell proteins. On the basis of phylogenetic and phenotypic evidence, it
is proposed that the unknown bacterium be classified as Facklamia ignava sp. nov.
The type strain of Facklamia ignava is CCUG 37419.
PMID- 9650989
TI - Molecular epidemiology of reemergent Vibrio cholerae O139 Bengal in India.
AB - We report the prevalence of the O139 serogroup in Calcutta, India, after its
reemergence in August 1996 and the spread of the reemerged clone to other parts
of the country by using previously established molecular markers. Phenotypically,
the reemerged Vibrio cholerae O139 displayed a difference compared to those that
appeared in late 1992 and 1993 in that the current O139 strains are sensitive to
co-trimoxazole. Ribotyping with the enzyme BglI produced two rRNA restriction
patterns in the O139 strains isolated after August 1996, and these patterns were
identical to those exhibited by strains of O139 isolated in 1992. Three clones of
V. cholerae O139 are currently prevailing in the country, with strains exhibiting
three bands after HindIII digestion and hybridization with a ctxA probe being
dominant. The reemergence of V. cholerae O139 in Calcutta after a 32-month
quiescent period reestablishes the O139 serogroup as an entity which is likely to
play a crucial role in the temporal antigenic variations among the serogroups of
V. cholerae causing cholera.
PMID- 9650990
TI - Differentiation of Rhizomucor species by carbon source utilization and isoenzyme
analysis.
AB - Nineteen Rhizomucor miehei and Rhizomucor pusillus isolates were assayed for
their ability to utilize 87 various substrates as a single carbon source. Besides
a difference in sucrose utilization, distinctive differences were found in the
utilization of glycine, phenylalanine, and beta-alanine. Five isoenzyme systems
also proved useful for the determination of markers of distinctive value at a
species level. Data were used to obtain information about the genetic
polymorphism of these species: a high degree of variability was found among the
R. pusillus isolates, whereas the group of R. miehei isolates was more
homogeneous genetically.
PMID- 9650992
TI - Streptococcus iniae, a human and animal pathogen: specific identification by the
chaperonin 60 gene identification method.
AB - It was recently reported that Streptococcus iniae, a bacterial pathogen of
aquatic animals, can cause serious disease in humans. Using the chaperonin 60
(Cpn60) gene identification method with reverse checkerboard hybridization and
chemiluminescent detection, we identified correctly each of 12 S. iniae samples
among 34 aerobic gram-positive isolates from animal and clinical human sources.
PMID- 9650991
TI - Fatal Hormonema dematioides peritonitis in a patient on continuous ambulatory
peritoneal dialysis: criteria for organism identification and review of other
known fungal etiologic agents.
AB - We report a fatal case a fungal peritonitis caused by the yeast-like dematiaceous
mould Hormonema dematioides in a 45-year-old woman. The woman had a 13-year
history of insulin-dependent diabetes mellitus and had been on continuous
ambulatory peritoneal dialysis for chronic renal failure. H. dematioides was
repeatedly isolated from the dialysate culture specimens collected on days 3, 9,
16, and 20 of her hospital stay. Preliminary culture reports on day 7 of the
growth of a yeast-like fungus, a probable Candida species, prompted the
administration of fluconazole (FLU). Intraperitoneal and intravenous FLU failed
to eliminate the mould, and the patient expired on day 21 of her hospital stay.
We use this case to present what appears to be the first report of fungal
peritonitis due to H. dematioides, to provide laboratorians with criteria for
differentiating this organism from the similar mould Aureobasidium pullulans and
from various yeast genera, and to provide a review of known fungal taxa inciting
peritonitis.
PMID- 9650993
TI - Molecular cloning and DNA sequencing of the Staphylococcus aureus UDP-N
acetylmuramyl tripeptide synthetase (murE) gene, essential for the optimal
expression of methicillin resistance.
AB - The Tn551 insertion in mutant RUSA235 of a highly methicillin resistant
Staphylococcus aureus strain results in drastic reduction in the level of
methicillin resistance and abnormalities, both in the composition of the
peptidoglycan and of the cell wall precursor pool. Cloning and sequencing of the
inactivated gene indicates that it is the murE gene of Staphylococcus aureus.
PMID- 9650994
TI - Characterization of a mutationally altered dihydropteroate synthase contributing
to sulfathiazole resistance in Escherichia coli.
AB - A series of Escherichia coli strains were selected for increasing resistance to
sulfathiazole. Resistance occurred in seven increments, suggesting the
accumulation of several mutations that contributed to overall sulfathiazole
resistance. All of the resistant strains had a sulfathiazole-resistant
dihydropteroate synthase with a Pro to Ser substitution at amino acid position
64. Overproduction of the wild-type enzyme did not result in sulfathiazole
resistance, however overproduction of the mutant enzyme resulted in significant
resistance. Conversely, overproduction of the wild-type enzyme in a sulfathiazole
resistant background resulted in a decrease in resistance. Although the specific
activity of DHPS in crude extracts was not significantly different from the wild
type, the amino acid substitution resulted in an enzyme with a tenfold increase
in the Km for p-aminobenzoate, and a 100-fold increase in the Ki for
sulfathiazole.
PMID- 9650995
TI - Limiting the spread of penicillin-resistant Streptococcus pneumoniae: experiences
from the South Swedish Pneumococcal Intervention Project.
AB - In an attempt to limit the spread of penicillin-resistant pneumococci (PRP), an
intervention project was initiated in the Malmohus County, southern Sweden in
January 1995. The ongoing project combines traditional communicable disease
control measures and actions aiming at reducing antibiotics consumption. All
patients in the county with a nasopharyngeal culture positive for PRP with MIC of
Penicillin G > or =0.5 mg/L are followed with nasopharyngeal cultures until PRP
negative. Nasopharyngeal cultures are obtained from family members and close
contacts of the index cases. Preschool children carrying PRP are denied
attendance at group day-care. From January 1995 to March 1997, 1,038 PRP-carriers
(429 index cases and 609 contact cases) were identified. Children aged 1-6 years
dominated (83%). Antibiotics sales decreased during the study period, and
epidemiologic data indicate that the intervention may have limited the
dissemination of PRP in the county, but further evaluation is needed.
PMID- 9650996
TI - Spread of the multiresistant Iberian clone of methicillin-resistant
Staphylococcus aureus (MRSA) to Italy and Scotland.
AB - The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus
aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as
the strain responsible for the massive 1989 outbreak of MRSA disease in the
hospital Princeps d'Espanya, Barcelona, Spain. Most Iberian MRSA carry a
constitutive beta-lactamase. They are resistant to most beta-lactam antibiotics,
macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are
susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim
and vancomycin. The characteristic DNA fingerprints of the clone include the mecA
polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction
pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the
lack of the mecI regulatory gene and a homogeneous, high level of expression of
methicillin resistance. Molecular surveillance studies have documented the
extensive spread of this clone to many Portuguese hospitals during the 1990s. In
this article, we describe the spread of the Iberian MRSA to hospitals in Rome,
Italy, and Scotland.
PMID- 9650997
TI - Molecular epidemiology of antibiotic resistance genes in multiresistant epidemic
Salmonella typhimurium DT 104.
AB - The epidemiology of antibiotic resistance genes in epidemic multiresistant S.
typhimurium DT 104 of human and animal origin was investigated. DNA prepared from
45 human and 21 animal strains isolated between 1984 and 1997, including eight
isolated in other European countries, the USA, Trinidad, and South Africa and
resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides,
spectinomycin, tetracyclines (R-type ACSSuSpT) were examined for the presence of
integrons by PCR. Integron hot spots were observed in all strains conferring
resistance to ACSSuSpT in two copies, determined by two discrete bands of
approximately 1.0 and 1.2 kb. Direct nucleotide sequencing of the individual
amplicons of selected strains indicated that the 1.0 kb gene product was ant (3")
Ia, responsible for resistance to streptomycin and spectinomycin; the 1.2 kb
amplicon contained the gene blaPSE-1, encoding the beta-lactamase PSE-1 (CARB-2).
Both integrons were encoded on a single XbaI macrorestriction fragment of
approximately 10 kb. All isolates of DT 104 of this resistance phenotype
contained the same inserted gene cassettes, irrespective of source and country of
origin, supporting the suggestion of the spread of an epidemic clone. Sequence
analysis of the quinolone resistance determining region (QRDR) of gyrA of 15
multiresistant strains conferring additional resistance to nalidixic acid and
ciprofloxacin (R-type ACSSuSpTNxCp) identified two discrete base substitutions at
codon Asp-87. Conversion of Asp-87 --> Asn was most commonly observed, in 7/10
human and 4/5 animal isolates, suggesting that this codon plays a major role in
the development of ciprofloxacin resistance in multiresistant S. typhimurium DT
104.
PMID- 9650998
TI - Trends in antibiotic resistance of staphylococci over an eight-year period:
differences in the emergence of resistance between coagulase positive and
coagulase-negative staphylococci.
AB - The antimicrobial susceptibilities of 1058 Staphylococcus aureus and 2,163
coagulase-negative staphylococci (CNS) isolates obtained from clinical specimen
between 1988 and 1995, were determined against 13 anti-staphylococcal
antibiotics. During the study period the resistance of Staphylococcus aureus to
ciprofloxacin, ceftazidime, and norfloxacin increased significantly by 7%, 4%,
and 6%, respectively (p < or = 0.001). By comparison, the antibiotic resistance
of CNS to ceftazidime, oxacillin, norfloxacin, ciprofloxacin, fusidic acid, and
cefoxitin increased by 20%, 17%, 15%, 14%, 12% and 10%, respectively (p < or =
0.001). Invasive and noninvasive S. aureus had similar antibiotic resistance,
whereas CNS invasive isolates were more resistant than noninvasive isolates to
every antibiotics, except vancomycin and fusidic acid. These differences were
significant (p < 0.001) for oxacillin, cefoxitin, and clindamycin. Our
observations confirm that staphylococci and particularly CNS isolates show an
important rate of increased resistance to the standard antimicrobials used for
therapy, and that the rate of emergence of resistance differ considerably between
coagulase-positive and coagulase-negative staphylococci.
PMID- 9650999
TI - Antimicrobial susceptibility profiles of oropharyngeal viridans group
streptococci isolates from cystic fibrosis and non-cystic fibrosis patients.
AB - The antimicrobial susceptibility profile of 77 oropharyngeal viridans
streptococci isolates from 34 cystic fibrosis (CF) patients and 58 isolates from
43 healthy non-CF patients were studied by the E-test and the standard disk
diffusion methods. Overall penicillin and cefotaxime resistances (intermediate
plus resistant isolates) were significantly higher (p < 0.05) among CF isolates
(72.7% and 45.5%, respectively) than among non-CF isolates (51.7% and 15.5%,
respectively). No significant difference was observed in overall (intermediate
plus resistant) erythromycin resistance rates, although high-level erythromycin
resistance (> or =32 microg/mL) was more frequently found in CF isolates (24.6%)
than in non-CF isolates (12.1%). An unexpected high percentage of isolates showed
low level erythromycin resistance (MIC range, 0.5-15 microg/mL): 41.5% in cystic
fibrosis and 46.5% in non-CF isolates. No significant differences were observed
regarding the percentage of colonized patients with at least one penicillin
resistant isolate. On the contrary, colonization with cefotaxime (p < 0.001) or
erythromycin (p = 0.014) resistant isolates were significantly more prevalent in
CF patients. Similar tetracycline and chloramphenicol resistance rates were
observed for both groups. Viridans isolates resistant to a single antibiotic were
more prevalent among non-CF patients and multiple resistance was higher among CF
patients. Prior antibiotic exposure could result in differences in beta-lactam
resistance and colonization rates with resistant isolates between both groups.
None of the non-CF patients was previously treated with antimicrobials for a
period of three months before sampling. In contrast, 94.1% of CF patients were
treated with antimicrobials within the same period; 65.6% with beta-lactam
antibiotics. Patients with CF disease, frequently exposed to antimicrobials, may
be a reservoir of viridans streptococci isolates with resistance determinants,
particularly to beta-lactam antibiotics.
PMID- 9651000
TI - Phase variation in colony opacity by Streptococcus pneumoniae.
PMID- 9651001
TI - Association between decreased susceptibility to a new antibiotic for treatment of
human diseases, everninomicin (SCH 27899), and resistance to an antibiotic used
for growth promotion in animals, avilamycin.
AB - The emergence of multiresistant bacteria has increased the need for new
antibiotics or modifications of older antibiotics. One promising agent might be
the everninomicin SCH 27899, an oligosaccharide antibiotic recently developed by
Schering Plough. However, another oligosaccharide, avilamycin, that is
structurally very similar has been used as a growth promoter for food animals in
the EU for several years, and a very frequent occurrence of resistance to
avilamycin has been found among Enterococcus faecium isolates from broilers in
Denmark. This study was conducted to investigate whether the resistance to
avilamycin was associated with decreased susceptibility to everninomicin. From
broilers, a total of 31 avilamycin susceptible and 55 avilamycin resistant (MIC
>16 microg/mL) E. faecium isolates were selected. From pigs, 21 avilamycin
susceptible and eight avilamycin-resistant Enterococcus faecalis and 50
avilamycin-susceptible and two avilamycin-resistant E. faecium isolates were
selected. All isolates were tested for susceptibility to everninomicin by E-test.
The avilamycin-susceptible enterococci isolates had MICs to everninomicin from
0.064 to 0.75 microg/mL (MIC50 = 0.38 microg/mL) and the avilamycin-resistant
isolates had MICs from 1.5 to 16 microg/mL (MIC50 = 3 microg/mL). Complete
agreement between decreased susceptibility to avilamycin and everninomicin was
found. This study showed that the use of avilamycin as a growth promoter for
broilers and pigs has created a reservoir of E. faecium and E. faecalis isolates
with decreased susceptibility to everninomicin among food animals already before
this antibiotic have been finally developed for human use.
PMID- 9651002
TI - Early formation of sexually dimorphic glomeruli in the developing olfactory lobe
of the brain of the moth Manduca sexta.
AB - The antennal lobes (ALs), the primary olfactory centers, of the moth Manduca
sexta are sexually dimorphic. Only ALs of males possess the macroglomerular
complex (MGC), the site of primary processing of information about the female's
sex pheromone. To understand the development of identified, odor-specific
olfactory glomeruli, we investigated the cellular events involved in the
morphogenesis of the MGC by means of various fluorescence staining techniques and
laser-scanning confocal microscopy. The MGC lies near the entrance of the
antennal nerve into the AL of the adult male and comprises three glomeruli, the
globular cumulus and two toroidal structures. The MGC forms during early stages
of metamorphic adult development through a stereotyped sequence of coordinated
changes in MGC-specific receptor axons, glial cells, and early-ingrowing
projection neurons of the medial group of AL neurons. The MGC divisions are the
earliest glomeruli to form in the male AL, and their basic organization is
established within about 3 days after ingrowth of the first sensory axons.
Despite their special anatomical features, the MGC glomeruli develop in a manner
similar to that of the ordinary glomeruli. Comparison of the ALs of males and
females reveals that two relatively large and early-developing glomeruli that are
situated dorsolaterally in the female AL appear to be female-specific.
Development of the sexually dimorphic glomeruli diverges immediately after the
ingrowth of the first olfactory receptor axons, resulting in the formation of
these large glomeruli in females and the MGC in males.
PMID- 9651003
TI - Characterisation of the adventitial rectal ganglia in the male rat by their
immunohistochemical features and projections.
AB - In recent years, considerable progress has been made in characterising the neural
circuitry of the pelvic plexus, particularly in the male rat. However, the small
ganglia on the adventitial surface of the rectum remain largely unstudied. We
have used immunohistochemistry and retrograde tracing techniques to determine the
content and projections of these neurons. The adventitial ganglia contain 600
1,000 neurons. All of these are immunoreactive for choline acetyltransferase, 44%
are immunoreactive for calbindin, and 35% are immunoreactive for vasoactive
intestinal peptide. Very few (1-5%) adventitial neurons contain tyrosine
hydroxylase or neuropeptide Y. In contrast, most adventitial neurons are
surrounded by varicose axons that do contain tyrosine hydroxylase or neuropeptide
Y. Retrograde tracing studies showed that the primary targets of adventitial
neurons within the bowel are the internal anal sphincter and the circular muscle
directly adjacent to the sphincter. However, more adventitial neurons project out
of the gut wall than to targets within the bowel. These are most likely to be
viscerofugal and rectospinal neurons. Combining the immunohistochemical and
tracing observations, these studies suggest that the rat adventitial ganglia do
not represent an additional source of pelvic (autonomic postganglionic) neurons
but, instead, that they are comprised primarily of viscerofugal and rectospinal
neurons. This is very different from the adventitial rectal ganglia of the cat,
which represent merely an extension of the pelvic plexus.
PMID- 9651004
TI - Developmental changes in human cerebellum: expression of intracellular calcium
receptors, calcium-binding proteins, and phosphorylated and nonphosphorylated
neurofilament protein.
AB - Few recent data are available on the development of the precise projection maps
of the cerebellar cortex in humans. To address this topic, we studied temporal
and spatial distribution of several antigens involved in calcium (Ca)-dependent
processes: the intracellular Ca receptors, inositol 1,4,5-trisphosphate receptor
type 1 (IP3R1) and ryanodine receptor (RyR); the Ca-binding proteins, calbindin D
28k (CB), parvalbumin (PV), and synaptophysin; and phosphorylated (SMI 31) and
nonphosphorylated (SMI 32) forms of neurofilament protein. All antigens were
studied in the human cerebellum during intrauterine development. The results of
this study show that immunocytochemical markers appeared in the following
sequence: CB and both forms ofneurofilament protein were observed at 4-5
gestational weeks (g.w.), PV appeared in the external granular layer and in a few
Purkinje cells at 11 g.w., a diffuse immunostaining for IP3R1 and synaptophysin
were observed at 13 g.w., whereas RyR was observed at 17-18 g.w. From 24 g.w. on,
Purkinje cells expressed all four examined markers of intracellular Ca signaling
as well as two forms of neurofilament protein. At the same time, compartmentation
of the Purkinje cell layer was detected with three intracellular Ca-signaling
molecules (IP3R1, CB, and PV) and with SMI 32. These results indicate that the
developmentally regulated expression of antigens studied here may play a role in
establishing a highly regular organization of terminal fields in the human
cerebellar cortex. Moreover, the initial expression of these antigens is
correlated temporally with other developmental processes in the cerebellum, such
as cellular maturation, revealed by the immunoreaction to cytoskeletal protein,
and synaptogenesis, revealed by immunoreaction to synaptophysin.
PMID- 9651005
TI - Projections from substantia nigra and zona incerta to the cat's nucleus of
Darkschewitsch.
AB - The goal of the present experiments was to examine the relationships of the
nucleus of Darkschewitsch (ND) with the substantia nigra pars reticulata (SNr),
the zona incerta (ZI), and the oculomotor nuclei by using wheat germ agglutinin
horseradish peroxidase (WGA-HRP) as a retrograde and anterograde neuronal tracer
injected into various sites of the cat's brain. To eliminate the possibility that
fibres of passage from the motor cortex passing through the SNr and ZI were
responsible for the ND label, WGA-HRP also was injected into the SNr or the ZI
after a large area of the frontal cortex, including the motor area, was
destroyed. Retrograde axonal transport demonstrated that many cells of the
rostromedial part of the ZI project to the ND, with the ipsilateral projections
being dominant. Some cells of the caudomedial part of the SNr project to the ND,
again, with the ipsilateral projection being dominant. A few small cells in the
ND project bilaterally to the oculomotor nucleus. Anterograde tracer demonstrated
that the SNr-ND terminal fields are less dense than the ZI-ND terminal fields. A
few fine terminal fibres were observed bilaterally in the oculomotor, trochlear,
and abducens nuclei. Electron microscopic examination demonstrated that these
fine, labelled terminals contain pleomorphic vesicles and have symmetrical
synaptic contacts with dendrites. These results indicate that the ND, a structure
that is known to be important for the control of axial muscles (i.e., eye, head,
and body muscles), is the target of projections from restricted areas of the SNr
and ZI: areas that, during saccadic eye movement, may lead to disinhibition of
the ND-oculomotor projection. Accordingly, the ND may function to inhibit the
activity of extraocular muscles during saccades.
PMID- 9651006
TI - Differences in developmental cell death between somatic and autonomic motor
neurons of rat spinal cord.
AB - Considerable knowledge concerning developmental cell death has come from the
study of somatic motor neurons (SMNs), but a related set of spinal neurons, the
autonomic motor neurons (AMNs), have been studied less extensively in this
respect. In the present study, we used three different approaches to determine
the amount of AMN cell death during normal development in the rat. First, target
dependency was studied in organotypic slice cultures, and it was found that AMNs
survived for at least 12 days after removal of their postsynaptic targets. No
factors were added to the serum-free medium to substitute for the ablated
targets, indicating that AMNs were able to survive without target-derived trophic
factors. Such target-independent survival is not characteristic of neurons that
undergo typical developmental cell death. Second, AMNs were counted in double
stained choline acetyltransferase immunocytochemical and NADPH diaphorase
histochemical preparations at ages (postnatal days 4-22) encompassing the period
when AMN postsynaptic target cells undergo developmental death. Neuron numbers
were essentially identical at all ages examined, indicating that no AMN cell
death occurred postnatally. Finally, from embryonic day 13 to postnatal day 22,
animals were analyzed by using terminal transferase-mediated nick-end labeling to
identify dying cells. Many fewer labeled cells were observed among AMNs than
among SMNs. Thus, all three approaches indicated that there is a significant
SMN/AMN difference in developmental cell death. The phenotypic trait(s) that
underlies this difference may also be important in the relative resistance of
AMNs to pathological conditions that induce death of SMNs, e.g., those involved
in amyotrophic lateral sclerosis and excitotoxicity.
PMID- 9651007
TI - Area-specific laminar distribution of cortical feedback neurons projecting to cat
area 17: quantitative analysis in the adult and during ontogeny.
AB - Corticocortical pathways can be classified as feedback and feedforward, in part
according to the laminar distribution of the parent cell bodies. Here, we have
developed exhaustive sampling procedures to determine unambiguously this laminar
distribution. This shows that individual extrastriate areas in the adult cat have
highly stereotyped proportions of supragranular layer neurons with respect to the
total population of neurons back-projecting to area 17. During development, these
adult laminar patterns emerge from an initially uniform radial distribution
through a process of selective reorganization, which is highly specific to each
area. Injections of fluorescent retrograde tracers were made in area 17. In areas
19, 20, posteromedial lateral suprasylvian area, and anteromedial lateral
suprasylvian area, we defined a projection zone as the region containing
retrogradely labeled neurons. In the neonate, counts of labeled neurons
throughout the projection zones show constant percentages of 40% in the
supragranular layers. During development, there is an area-specific reduction in
the percentage of supragranular labeled neurons generating the laminar
distributions characteristic of each area. Numbers of labeled neurons were
estimated at different eccentricities of the projection zone. This finding
indicates that during development there is a relative decrease in the numbers of
labeled neurons of the periphery of the projection zone in the supragranular
layers but not in the infragranular layers. This decrease is accompanied by a
relative decrease in the dimensions of the supragranular projection zone with
respect to the infragranular projection zone. These findings suggest that each
extrastriate area precisely adjusts the proportions of supragranular layer
neurons back-projecting to striate cortex in part by developmental changes in the
divergence-convergence values of individual neurons. This shaping of
corticocortical connectivity occurs relatively late in postnatal development and
could, therefore, be under epigenetic control.
PMID- 9651008
TI - Expression of differential immune factors in temporal cortex and cerebellum: the
role of alpha-1-antichymotrypsin, apolipoprotein E, and reactive glia in the
progression of Alzheimer's disease.
AB - A variety of factors and processes have been implicated in the development and
progression of the pathology of Alzheimer's Disease (AD), including amyloid
fragment deposition, reactive gliosis, alpha-1-antichymotrypsin (ACT), and
apolipoprotein E (APOE). Carriers of the APOE 4 allele have been shown to have an
enhanced risk of developing AD, and the ACT signal peptide A/A genotype may
modify the APOEepsilon4 risk. The protein products of these genes have been shown
to enhance conversion of diffuse beta amyloid (Abeta) fibrils, which are found in
diffuse plaques, to the fibrillar form found in neuritic plaques. In affected
regions of AD brain, ACT and APOE colocalize with Abeta deposits and reactive
microglia and astrocytes. We examined the regional distribution of ACT, APOE, and
reactive glia in temporal cortex, where neuritic plaques are abundant, and
cerebellum (in areas where diffuse plaques but not neuritic plaques accumulate)
to examine the relationship of these markers to the deposition of Abeta. In
temporal cortex, ACT and APOE staining was localized to plaque-like profiles,
reactive astrocytes, and blood vessels; human leukocyte antigen-DR (HLA-DR) and
glial fibrillary acidic protein (GFAP) staining revealed focal clusters of
reactive microglia and astrocytes. In cerebellum, ACT and APOE immunoreactivity
was never localized to plaque-like profiles but was weakly localized to
unreactive astrocytes; weak HLA-DR and GFAP immunoreactivity was present on
quiescent microglia throughout the cerebellum. The lack of fibrillar amyloid
deposits in cerebellum, despite the presence of well-characterized markers
thought to mediate the production of Abeta, suggests that this brain region may
be lacking certain factors necessary for fibril formation or that the cerebellum
responds differently to stimuli that successfully mediate inflammation in
affected cortex.
PMID- 9651009
TI - Comparison of cortically and subcortically controlled motor systems: I.
Morphology of intracellularly filled rubrospinal neurons in rat and turtle.
AB - The rat and turtle differ markedly in major structural features of the
corticocerebellorubrospinal circuitry. Although both species have a well
developed cerebellorubrospinal system, they differ in that a direct cerebral
cortical input to the red nucleus is present only in the rat. The aim of the
present study was to compare features of the soma and dendritic morphology of
rubrospinal neurons that receive cortical input, as in rats, with those that do
not, as in turtles. Intracellular Lucifer Yellow injections of neurons
retrogradely labeled with Fast Blue in the rat or activity-dependent
sulforhodamine-labeled neurons in the turtle were used to fill rubrospinal
neurons in 150-200-microm-thick fixed sections. Images of filled neurons were
imported into a computer to analyze quantitatively soma and dendritic morphology.
The results show that rubrospinal soma size is slightly larger in the rat than in
the turtle. However, analysis of the dendritic morphology, including total
dendritic length, length of primary, secondary, and tertiary dendritic branches,
and a Scholl analysis of dendritic branch intersections across concentric rings,
demonstrated no significant differences between the two species. These findings
suggest that the basic dendritic morphology of rubrospinal neurons may have been
established early in phylogeny, preceding the evolution of cortical inputs.
Alternatively, similar dendritic morphologies may have arisen due to the presence
of other synapses in the turtle that occupy the sites of the cortical input in
the rat. This comparative approach provides insights into the information
processing capabilities of cortically versus subcortically controlled motor
systems.
PMID- 9651010
TI - Patterns of brainstem projection to the thalamic reticular nucleus.
AB - To understand better how the brainstem may influence thalamocortical activity, we
have examined the projection patterns of different brainstem nuclei to the
thalamic reticular nucleus. Iontophoretic injections of biotinylated dextran were
made into various nuclei of the brainstem (superior colliculus, periaqueductal
grey matter, parabrachial nucleus, pedunculopontine tegmental nucleus,
laterodorsal tegmental nucleus, substantia nigra, ventral tegmental area, and
locus coeruleus) of Sprague-Dawley rats by using stereotaxic coordinates. Our
results show that afferents from each brainstem nucleus make distinct zones
within the reticular nucleus. For example, the superior colliculus projects
largely to the dorsal parts of the reticular nucleus, whereas the
pedunculopontine nucleus projects to the ventral parts of the reticular nucleus.
The substantia nigra, on the other hand, projects to the ventrolateral edge of
the reticular nucleus. We also examined the distribution of these brainstem
afferents within the dorsal thalamus and compared these distributions with those
seen in the reticular nucleus. We found three different patterns. First, a given
brainstem nucleus projects to a particular dorsal thalamic nucleus as well as to
the corresponding, functionally associated, reticular sector (e.g., from the
substantia nigra). Second, a given brainstem nucleus projects to a particular
dorsal thalamic nucleus but not to the corresponding reticular sector (e.g., from
the superior colliculus). Finally, a given brainstem nucleus projects to a given
reticular sector but not to the corresponding dorsal thalamic nucleus (e.g., from
the midbrain reticular nucleus). In general, our results indicate that various
brainstem nuclei project to particular territories of the thalamic reticular
nucleus. Through these reticular projections, brainstem nuclei may influence
distinct thalamocortical pathways in addition to those that are influenced by
their direct projection to the dorsal thalamus.
PMID- 9651011
TI - Patterns of connections between zona incerta and brainstem in rats.
AB - To understand better the organisation of zona incerta of the thalamus, this study
has examined the patterns of connections that this nucleus has with various
nuclei of the brainstem. Injections of biotinylated dextran or cholera toxin
subunit B were made into the dorsal raphe, midbrain reticular nucleus,
pedunculopontine tegmental nucleus, periaqueductal grey matter, pontine reticular
nucleus, substantia nigra, superior colliculus, and ventral tegmental area of
Sprague-Dawley rats, and their brains were processed by using standard tracer
detection methods. In general, our results show that zona incerta forms the major
zone in the thalamus where these ascending brainstem axons terminate and from
which descending axons that travel back to these same brainstem centres
originate. These incertal inputs and outputs are limited largely to a distinct
sector of zona incerta, the dorsal sector. An exception to this pattern is
evident in the incertal projection to the deep layers of the superior colliculus;
this projection, unlike all of the others, arises from cells in the ventral
sector of zona incerta. Our results also show little evidence for a well-defined
topography of projection between the brainstem and the zona incerta. For
instance, small injections into each brainstem nucleus result in labelled
terminals and in cells spread throughout much of the dorsal sector of zona
incerta, with no local zone of concentration within the sector. Again, an
exception to this pattern is seen in the incertal projection to the superior
colliculus. This projection, unlike the others, shows a clear topographical
organisation: A medial-lateral shift in the injection site in the colliculus
results in a lateral-medial shift in the position of labelled cells in zona
incerta. Curiously, even though the incertal projection to the colliculus appears
to be mapped, the collicular projection back to zona incerta is not mapped. In
conclusion, then, a number of brainstem nuclei (except for the deep collicular
layers) have strong and overlapping connections within the same sector of zona
incerta. This convergence of many functionally diverse brainstem afferents within
zona incerta places this nucleus in a strategic position to sample the general
activity of the brainstem and, perhaps, acts as a relay of this information to
higher centres, such as the dorsal thalamic relay nuclei and the cerebral
hemispheres.
PMID- 9651012
TI - A model for the fluid motion of vitreous humour of the human eye during saccadic
movement.
AB - During saccadic motion the eyewall moves in a manner similar to a sinusoid or at
least can be represented by a sine Fourier series. Motion of the vitreous is
induced by the saccade and the vitreo-retinal interface is subjected to a time
dependent shear. This force may be a significant factor for retinal tearing in
the neighbourhood of small retinal holes or tears. An analytical viscoelastic
model and a numerical, Newtonian model of the motion of the vitreous are
presented and compared. Under sinusoidal boundary motion the analytical model
shows that a viscous wave propagates inward toward the axis of rotation and the
characteristic length of this wave is a function of the Womersley number. The
numerical solution indicates that the vitreous moves similarly to the analytical
result with small secondary motion; however, this motion allows complete
recirculation of the vitreous over large timescales. Excellent agreement is found
between the analytical and numerical models. The time-dependent fluid shear is
evaluated and from the analytical solution the maximum value of this is found to
be proportional to R0 square root of v(omega)3, where R0 is the eye radius, v the
modified complex viscosity and omega the sinusoidal frequency. This indicates
that myopes have a larger shear force exerted on them by virtue of the larger eye
size. Further work is directed toward a model which links the stress found in the
sclera to that exerted on the vitreo-retinal interface by the vitreous fluid
motion.
PMID- 9651013
TI - A data reduction scheme for improving the accuracy of oxygen saturation
calculations from spectrometric in vivo measurements.
AB - A developing tool in ophthalmological research and practice is the study of the
oxygen saturation in retinal vessels because this measurement contains important
diagnostic information about the metabolism at the human ocular fundus. Imaging
spectrometry enables locally resolved measurements of the oxygen saturation
simultaneously in arteries and veins. The vessel reflex, imaging errors of the
detection system and the noise of the signal result in substantial uncertainties
in the calculated data. We present a data processing method for the improvement
of the primary information leading to a reduction of the uncertainties of the
derived oxygen saturation.
PMID- 9651014
TI - Monte Carlo simulation of source-excited in vivo x-ray fluorescence measurements
of heavy metals.
AB - This paper reports on the Monte Carlo simulation of in vivo x-ray fluorescence
(XRF) measurements. Our model is an improvement on previously reported
simulations in that it relies on a theoretical basis for modelling Compton
momentum broadening as well as detector efficiency. Furthermore, this model is an
accurate simulation of experimentally detected spectra when comparisons are made
in absolute counts; preceding models have generally only achieved agreement with
spectra normalized to unit area. Our code is sufficiently flexible to be applied
to the investigation of numerous source-excited in vivo XRF systems. Thus far the
simulation has been applied to the modelling of two different systems. The first
application was the investigation of various aspects of a new in vivo XRF system,
the measurement of uranium in bone with 57Co in a backscatter (approximately 180
degrees) geometry. The Monte Carlo simulation was critical in assessing the
potential of applying XRF to the measurement of uranium in bone. Currently the
Monte Carlo code is being used to evaluate a potential means of simplifying an
established in vivo XRF system, the measurement of lead in bone with 57Co in a 90
degrees geometry. The results from these simulations may demonstrate that
calibration procedures can be significantly simplified and subject dose may be
reduced. As well as providing an excellent tool for optimizing designs of new
systems and improving existing techniques, this model can be used in the
investigation of the dosimetry of various XRF systems. Our simulation allows a
detailed understanding of the numerous processes involved when heavy metal
concentrations are measured in vivo with XRF.
PMID- 9651015
TI - Electrochemical study of insulating properties of dental amalgam bonding
polymers.
AB - The standard techniques used for amalgam restorations often result in a lack of
adhesion to mineralized dental tissues. The bonding of amalgam with polymer has
been suggested to improve its adaptation to dental tissues. Moreover the polymer
involved in the bonding should inhibit the corrosion and the diffusion of
metallic ions. The aim of this study was to evaluate in vitro the capacity of
bonded amalgam to prevent ionic diffusion and migration. In this respect, an
original method employing electrochemical techniques was used to determine the
leakage current of bonded amalgam restorations. The electrochemical behaviour of
conventional and bonded amalgam restorations was compared using a potentiostat
driven by a computerized system (Voltamaster, Radiometer Analytical) with
software for specific applications such as chronoamperometry or cyclic
voltammetry. Samples of recently extracted teeth of young patients were first
examined, and then the results were checked by other experimental assays using
protected and unprotected copper sticks. The measurements obtained with
chronoamperometry (E = +300 mV/SCE) in Ringer's solution at 37 degrees C showed
that after polarization for 30 h the oxidation current decreased threefold for
bonded samples (10 microA cm(-2)) as compared with the unprotected samples (35
microA cm(-2)). These results, as well as those obtained with the copper wires,
demonstrated that even with two layers of adhesive the bonded joint is permeable
to ions probably as a result of the hydrophylic properties of HEMA, a component
of the adhesive. However, using five layers of adhesive reduced the ionic current
by a factor as large as 10(6).
PMID- 9651016
TI - A novel equivalent circuit model for gap-connected cells.
AB - Gap junctions connect neighbouring cells, providing the intercellular
communication that is essential for cell growth regulation, for example. There is
some evidence that gap communication changes upon exposure to electromagnetic
(EM) fields. In previous work, we performed detailed finite element method (FEM)
modelling of gap junction connected cells exposed to EM fields. For cell
configurations, the presence of gap junctions influences the transmembrane
potential and its frequency behaviour. The relaxation frequency cannot be
accurately predicted by previously developed simplified models. We present a
novel equivalent circuit model (ECM) that incorporates more detailed models of
the gaps, and compare results obtained with this ECM to finite element and leaky
cable (LC) model results. Our ECM provides more accurate estimates of the
frequency behaviour of cells than the leaky cable model. Also, our ECM results
suggest limitations of the application of simple models to gap-connected cells:
with higher gap resistivity, the current flow in the cell interiors becomes
increasingly complex and is not well represented by simple models. In this case,
techniques such as the finite element method are required to model accurately
cell behaviour.
PMID- 9651017
TI - Value of epicardial potential maps in localizing pre-excitation sites for
radiofrequency ablation. A simulation study.
AB - Using computer simulations, we systematically investigated the limitations of an
inverse solution that employs the potential distribution on the epicardial
surface as an equivalent source model in localizing pre-excitation sites in Wolff
Parkinson-White syndrome. A model of the human ventricular myocardium that
features an anatomically accurate geometry, an intramural rotating anisotropy and
a computational implementation of the excitation process based on electrotonic
interactions among cells, was used to simulate body surface potential maps
(BSPMs) for 35 pre-excitation sites positioned along the atrioventricular ring.
Two individualized torso models were used to account for variations in torso
boundaries. Epicardial potential maps (EPMs) were computed using the L-curve
inverse solution. The measure for accuracy of the localization was the distance
between a position of the minimum in the inverse EPMs and the actual site of pre
excitation in the ventricular model. When the volume conductor properties and
lead positions of the torso were precisely known and the measurement noise was
added to the simulated BSPMs, the minimum in the inverse EPMs was at 12 ms after
the onset on average within 0.65 +/- 0.26 cm of the pre-excitation site. When the
standard torso model was used to localize the sites of onset of the pre
excitation sequence initiated in individualized male and female torso models, the
mean distance between the minimum and the pre-excitation site was 0.67 +/- 0.31
cm for the male torso and 0.82 +/- 0.53 cm for the female torso. The findings of
our study indicate that a location of the minimum in EPMs computed using the
inverse solution can offer non-invasive means for pre-interventional planning of
the ablative treatment.
PMID- 9651018
TI - Lung uptake of thallium-201: a marker of defect reversibility?
AB - High lung uptake of thallium-201 at stress is reported to be associated with a
large number of perfusion defects and poor prognosis. This study was performed to
assess whether the reversibility of stress perfusion defects was related to lung
uptake. Gated planar thallium scans at stress and at redistribution from 102
consecutive patients with essentially normal left ventricular ejection fraction
(using 99mTc gated blood pool ventriculography) were graded in terms of defect
size. Lung and myocardial uptake of thallium were quantitated by region of
interest methods relative to the given activity in a previously validated method.
There was no significant correlation (non-parametric) between lung uptake and
degree of redistribution (p = ns, rs = 0.140). There was a weak but positive
correlation between lung uptake and defect size (p < 0.05, rs = 0.188). Both
exercise time and double product showed a negative correlation with lung uptake
(e.g. for double product, p < 0.0005, rs = -0.541). In conclusion, contrary to
our expectation, lung uptake is not related to the degree of redistribution. High
lung uptake seems to reflect poor cardiovascular reserve.
PMID- 9651019
TI - Configuration options for intensity-modulated radiation therapy using multiple
static fields shaped by a multileaf collimator. II: constraints and limitations
on 2D modulation.
AB - This paper addresses the technique of using multiple static multileaf-collimator
shaped field components to create a two-dimensional intensity-modulated beam (2D
IMB). It addresses the physical constraints on the problem of determining the
optimum field-component leaf configurations under the circumstances that (i) the
static field components are shaped by leaves alone and (ii) the 2D intensity
distribution is delivered by exactly N field components when there are N rising
intensity equal-fluence increments in the 1D channel containing the maximum
fluence in the 2D IMB. This corresponds to the least inefficient delivery. In
general it is noted that an optimum solution (set of field-component leaf
configurations) with zero tongue-and-groove underdose may not exist (depending on
the distribution) and an exhaustive search for the set of leaf configurations
with the minimum tongue-and-groove underdose is impossible for realistically
sized problems. Against this background iterative methods to examine a limited
search space are shown to yield an optimum solution with zero tongue-and-groove
underdose for certain intensity distributions. These searches are not robust and
can be defeated. The problem of finding an optimum solution may be generally
insoluble for some 2D IMBs under the conditions (i) and (ii). If, however, a
larger number of field components is permitted and/or the accelerator jaws may
also be used, in addition to the multileaves, then an optimum solution with zero
tongue-and-groove underdose can always be found with lower efficiency.
PMID- 9651020
TI - Calculation of absorbed dose distributions from dynamic wedges.
AB - In radiotherapy with photon beams, the use of dynamic wedges, which are obtained
by the movement of one of the jaws, offers an increasing flexibility relative to
the traditional use of metal wedges. But it is a disadvantage for the measurement
of absorbed dose distributions, because the absorbed dose at each measurement
point can only be obtained after a complete movement of the jaw. Consequently,
for radiotherapy planning, an algorithm should be available that does not require
measurements for any specific dynamically wedged beam, but is based on only a
modest number of measurements. In this paper, an algorithm for the calculation of
the dose distribution from dynamic wedges is described. This algorithm uses the
convolution of pencil beam kernels with a non-uniform field function. These
pencil beam kernels are derived from empirical data resulting from measurements
of the open beam only.
PMID- 9651021
TI - Spectral reconstruction of clinical megavoltage photon beams and the implications
of spectral determination on the dosimetry of such beams.
AB - An analysis technique, based on simulated annealing, is described which is
employed to derive megavoltage photon beam spectral information from narrow beam
attenuation measurements. Megavoltage photon beam spectra have been determined
using this technique for linear accelerators from different manufacturers, and
different models from individual manufacturers at a range of energies from
nominal 6 MV to nominal 25 MV. All of the photon beams included in the study are
in routine clinical use. The subsequent effects on dosimetry of employing derived
primary spectra to specify beam quality are examined. The results suggest that
the quality index TPR(20)10 may be insensitive to beam quality changes for high
energy beams in the range of 15 MV to 25 MV. Although the quality index may be
insensitive as a beam quality specifier at these higher qualities, the actual
difference in the calculated dose delivered using derived spectra as the quality
specifier rather than TPR(20)10 is likely to be small, the results obtained
indicating a difference of between 0.2% and 0.7% in the calculated dose
delivered.
PMID- 9651022
TI - An evaluation of epoxy resin phantom materials for electron dosimetry.
AB - The use of epoxy resin 'solid water' (water substitute) phantoms is becoming
increasingly common in radiotherapy dosimetry, and depth ionization curves and
conversion factors from ionization to dose identical to water have often been
assumed. Fluence ratios of water to solid water for WTe (produced by Radiation
Physics, St Bartholomew's Hospital, London) and RMI 457 (produced by Radiation
Measurements Inc., Middleton, Wisconsin) have therefore been determined and have
been found to decrease with energy, which, within measurement uncertainty, can be
described with a linear function dependent on mean electron beam energy at the
depth of measurement, Ed. The fluence ratios for WTe are very close to unity
(i.e. within the measuring uncertainty) for most of the energies examined, the
exception being a nominal 20 MeV beam. The results also show that an assumption
of unity for the fluence ratios of RMI 457 may introduce a systematic error of
the order of 1% in electron beam dosimetry at lower energies. As regards the
depth ionization curves measured in the respective solid water materials, these
are shown to be in agreement with those measured in water within the limits of
the measuring uncertainty.
PMID- 9651023
TI - Dose accuracy check of the 3D electron beam algorithm in a treatment planning
system.
AB - The accuracy of the recently implemented three-dimensional electron beam dose
calculating algorithm in CADPLAN version 2.62 manufactured by Varian Dosetek was
investigated. The algorithm uses a generalized Gaussian pencil beam model and the
dose distributions are calculated as the sum of three weighted Gaussians. To use
the calculating program in an optimum way, one needs to know the dose calculation
accuracy of the algorithm as well as its limitations. This investigation includes
comparisons of measured relative dose distributions with calculated dose
distributions and also comparisons of measured and calculated monitor units. The
geometries tested were quadratic fields, irregularly shaped fields, oblique
fields, irregularly shaped phantom surfaces and internal heterogeneities and were
most often irradiated with 8 and 20 MeV electrons. The results indicate that the
algorithm is well suited for clinical three-dimensional dose planning. Some
deviations occurred but they were most often within the limits of international
criteria of acceptability.
PMID- 9651024
TI - Dose characteristics of in-house-built collimators for stereotactic radiotherapy
with a linear accelerator.
AB - Dose characteristics of a stereotactic radiotherapy unit based on a standard
Varian Clinac 4/100 4 MV linear accelerator, in-house-built Lipowitz collimators
and the SMART stereotactic radiotherapy treatment planning software have been
determined. Beam collimation is constituted from the standard collimators of the
linear accelerator and a tertiary collimation consisting of a replaceable
divergent Lipowitz collimator. Four collimators with isocentre diameters of 15,
25, 35 and 45 mm, respectively, were constructed. Beam characteristics were
measured in air, acrylic or water with ionization chamber, photon diode, electron
diode, diamond detector and film. Monte Carlo simulation was also applied. The
radiation leakage under the collimators was less than 1% at 50 mm depth in water.
Specific beam characteristics for each collimator were imported to SMART and dose
planning with five non-coplanar converging 140 degrees arcs separated by 36
degrees angles was performed for treatment of a RANDO phantom. Dose verification
was made with TLD and radiochromic film. The in-house-built collimators were
found to be suitable for stereotactic radiotherapy and patient treatments with
this system are in progress.
PMID- 9651025
TI - Dose rate constants for 125I, 103Pd, 192Ir and 169Yb brachytherapy sources: an
EGS4 Monte Carlo study.
AB - An exhaustive revision of dosimetry data for 192Ir, 125I, 103Pd and 169Yb
brachytherapy sources has been performed by means of the EGS4 simulation system.
The DLC-136/PHOTX cross section library, water molecular form factors, bound
Compton scattering and Doppler broadening of the Compton-scattered photon energy
were considered in the calculations. The absorbed dose rate per unit contained
activity in a medium at 1 cm in water and air-kerma strength per unit contained
activity for each seed model were calculated, allowing the dose rate constant
(DRC) A to be estimated. The influence of the calibration procedure on source
strength for low-energy brachytherapy seeds is discussed. Conversion factors for
125I and 103Pd seeds to obtain the dose rate in liquid water from the dose rate
measured in a solid water phantom with a detector calibrated for dose to water
were calculated. A theoretical estimate of the DRC for a 103Pd model 200 seed
equal to 0.669 +/- 0.002 cGy h(-1) U(-1) is obtained. Comparison of obtained DRCs
with measured and calculated published results shows agreement within 1.5% for
192Ir, 169Yb and 125I sources.
PMID- 9651026
TI - Shuttle dose at the Vienna Leksell Gamma Knife.
AB - The aim of this study was to determine the shuttle dose for all collimator
helmets (4, 8, 14 and 18 mm) of the Gamma Knife, model B, in Vienna, Austria. The
additional dose accumulated during the transport of the patient in and out of the
treatment position should be considered in the dose planning procedure of
multicentre treatment regimens and in fractionated stereotactic Gamma Knife
radiotherapy. The GafChromic film study was basically used to determine the
shuttle dose of all four collimator helmets. In addition, measurements with an
ionization chamber (18 and 14 mm collimator--and, for the 18 mm collimator
helmet, TLD dosimetry--were performed in order to confirm the GafChromic film
data. The shuttle dose ranged between 99.6 and 183.5 mGy, depending mainly on the
size of the collimator and the irradiated isocentres at the half-life activity of
Co-60 in a brand new Gamma unit. Our film-generated data were in good correlation
with the dose levels obtained with the ionization chamber and the TLD dosimetry,
showing a dose difference of less than 0.8%. Since it was possible to verify the
shuttle dose even for the 4 and 8 mm collimator helmets, we consider it a non
negligible factor and would advocate the inclusion of the shuttle dose in
radiosurgical dose planning.
PMID- 9651027
TI - The precision of proton range calculations in proton radiotherapy treatment
planning: experimental verification of the relation between CT-HU and proton
stopping power.
AB - The precision in proton radiotherapy treatment planning depends on the accuracy
of the information used to calculate the stopping power properties of the tissues
in the patient's body. This information is obtained from computed tomography (CT)
images using a calibration curve to convert CT Hounsfield units into relative
proton stopping power values. The validity of a stoichiometric method to create
the calibration curve has been verified by measuring pairs of Hounsfield units
and stopping power values for animal tissue samples. It was found that the
agreement between measurement and calibration curve is better than 1% if beam
hardening effects in the acquisition of the CT images can be neglected. The
influence of beam hardening effects on the quantitative reading of the CT
measurements is discussed and an estimation for the overall range precision of
proton beams is given. It is expected that the range of protons in the human body
can be controlled to better than +/-1.1% of the water equivalent range in soft
tissue and +/-1.8% in bone, which translates into a range precision of about 1-3
mm in typical treatment situations.
PMID- 9651028
TI - The equivalent square concept for the head scatter factor based on scatter from
flattening filter.
AB - The equivalent field relationship between square and circular fields for the head
scatter factor was evaluated at the source plane. The method was based on
integrating the head scatter parameter for projected shaped fields in the source
plane and finding a field that produced the same ratio of head scatter to primary
dose on the central axis. A value of sigma/R approximately equal to 0.9 was
obtained, where sigma was one-half of the side length of the equivalent square
and R was the radius of the circular field. The assumptions were that the
equivalent field relationship for head scatter depends primarily on the
characteristics of scatter from the flattening filter, and that the differential
scatter-to-primary ratio of scatter from the flattening filter decreases linearly
with the radius, within the physical radius of the flattening filter. Lam and co
workers showed empirically that the area-to-perimeter ratio formula, when applied
to an equivalent square formula at the flattening filter plane, gave an accurate
prediction of the head scatter factor. We have analytically investigated the
validity of the area-to-perimeter ratio formula. Our results support the fact
that the area-to-perimeter ratio formula can also be used as the equivalent field
formula for head scatter at the source plane. The equivalent field relationships
for wedge and tertiary collimator scatter were also evaluated.
PMID- 9651029
TI - An adaptive control algorithm for optimization of intensity modulated
radiotherapy considering uncertainties in beam profiles, patient set-up and
internal organ motion.
AB - A new general beam optimization algorithm for inverse treatment planning is
presented. It utilizes a new formulation of the probability to achieve
complication-free tumour control. The new formulation explicitly describes the
dependence of the treatment outcome on the incident fluence distribution, the
patient geometry, the radiobiological properties of the patient and the
fractionation schedule. In order to account for both measured and non-measured
positioning uncertainties, the algorithm is based on a combination of dynamic and
stochastic optimization techniques. Because of the difficulty in measuring all
aspects of the intra- and interfractional variations in the patient geometry,
such as internal organ displacements and deformations, these uncertainties are
primarily accounted for in the treatment planning process by intensity modulation
using stochastic optimization. The information about the deviations from the
nominal fluence profiles and the nominal position of the patient relative to the
beam that is obtained by portal imaging during treatment delivery, is used in a
feedback loop to automatically adjust the profiles and the location of the
patient for all subsequent treatments. Based on the treatment delivered in
previous fractions, the algorithm furnishes optimal corrections for the remaining
dose delivery both with regard to the fluence profile and its position relative
to the patient. By dynamically refining the beam configuration from fraction to
fraction, the algorithm generates an optimal sequence of treatments that very
effectively reduces the influence of systematic and random set-up uncertainties
to minimize and almost eliminate their overall effect on the treatment. Computer
simulations have shown that the present algorithm leads to a significant increase
in the probability of uncomplicated tumour control compared with the simple
classical approach of adding fixed set-up margins to the internal target volume.
PMID- 9651030
TI - An optimized leaf-setting algorithm for beam intensity modulation using dynamic
multileaf collimators.
AB - A leaf-setting algorithm is developed for generating arbitrary beam intensity
profiles in discrete levels using dynamic multileaf collimators (DMLCs). The
algorithm starts with the algebraic expression for the area under the beam
profile. It is shown that the coefficients in this expression can be transformed
into the specifications for the leaf-setting sequence. It is proven that the
algorithm optimizes beam delivery time and total monitor units for the DMLC leaf
setting for intensity modulated radiotherapy (IMRT). The algorithm is
demonstrated to be applicable to both the 'step-and-shoot' and 'dynamic' type of
beam delivery. The graphical interpretation and numerical implementation scheme
of the algorithm is illustrated using a simplified example.
PMID- 9651031
TI - Registration of synthetic tomographic projection data sets using cross
correlation.
AB - Tomographic registration, a method that makes possible accurate patient
registration directly from projection data, consists of three processing steps:
(i) manual coarse positioning, (ii) tomographic projection set acquisition, and
(iii) computer mediated refined positioning. In the coarse positioning stage, the
degree of patient alignment is comparable with that achieved with the standard
radiotherapy set-up. However, the accuracy requirements are somewhat more relaxed
in that meticulous alignment of the patient using external laser indicators is
not necessary. Instead, tomographic projection sets are compared with planning
CTs in order to achieve improved patient set-up. The projection sets are cross
correlated to obtain the best-fit translation and rotation offsets. The algorithm
has been tested on synthetic data with the incorporation of varying amounts of
Gaussian pseudo-random noise. These tests demonstrate the algorithm's stability
and also confirm that alignment can be achieved with an accuracy of less than one
projection pixel.
PMID- 9651032
TI - A new method to estimate parameters of linear compartmental models using
artificial neural networks.
AB - At present, the preferred tool for parameter estimation in compartmental analysis
is an iterative procedure; weighted nonlinear regression. For a large number of
applications, observed data can be fitted to sums of exponentials whose
parameters are directly related to the rate constants/coefficients of the
compartmental models. Since weighted nonlinear regression often has to be
repeated for many different data sets, the process of fitting data from
compartmental systems can be very time consuming. Furthermore the minimization
routine often converges to a local (as opposed to global) minimum. In this paper,
we examine the possibility of using artificial neural networks instead of
weighted nonlinear regression in order to estimate model parameters. We train
simple feed-forward neural networks to produce as outputs the parameter values of
a given model when kinetic data are fed to the networks' input layer. The
artificial neural networks produce unbiased estimates and are orders of magnitude
faster than regression algorithms. At noise levels typical of many real
applications, the neural networks are found to produce lower variance estimates
than weighted nonlinear regression in the estimation of parameters from mono- and
biexponential models. These results are primarily due to the inability of
weighted nonlinear regression to converge. These results establish that
artificial neural networks are powerful tools for estimating parameters for
simple compartmental models.
PMID- 9651033
TI - Application of distance-dependent resolution compensation and post-reconstruction
filtering for myocardial SPECT.
AB - Compensation for distance-dependent resolution can be directly incorporated in
maximum likelihood reconstruction. Our objective was to examine the effectiveness
of this compensation using either the standard expectation maximization (EM)
algorithm or an accelerated algorithm based on use of ordered subsets (OSEM). We
also investigated the application of post-reconstruction filtering in combination
with resolution compensation. Using the MCAT phantom, projections were simulated
for 360 degrees data, including attenuation and distance-dependent resolution.
Projection data were reconstructed using conventional EM and OSEM with subset
size 2 and 4, with/without 3D compensation for detector response (CDR). Also post
reconstruction filtering (PRF) was performed using a 3D Butterworth filter of
order 5 with various cutoff frequencies (0.2-1.2 cycles cm(-1)). Image quality
and reconstruction accuracy were improved when CDR was included. Image noise was
lower with CDR for a given iteration number. PRF with cutoff frequency greater
than 0.6 cycles cm(-1) improved noise with no reduction in recovery coefficient
for myocardium but the effect was less when CDR was incorporated in the
reconstruction. CDR alone provided better results than use of PRF without CDR.
Results suggest that using CDR without PRF, and stopping at a small number of
iterations, may provide sufficiently good results for myocardial SPECT. Similar
behaviour was demonstrated for OSEM.
PMID- 9651034
TI - Statistical distribution of factors and factor images in factor analysis of
medical image sequences.
AB - From a time or energy image sequence, factor analysis of medical image sequences
(FAMIS) estimates factors, representing kinetics or spectra in a given
physiological compartment, and associated factor images, showing the compartments
corresponding to each curve. In this paper, we show that the statistical
properties of factor images and associated factors can be determined using a well
known result from elementary probability theory. Numerical experiments are
conducted to demonstrate that the variance observed in factor images can be
predicted when the statistical properties of the original data are known. It is
shown how these theoretical results can be used to relax the non-negativity
constraints during FAMIS oblique analysis and to improve the quantitative
interpretation of the factor images by associating a confidence interval with
each pixel value.
PMID- 9651035
TI - Selection of task-dependent diffusion filters for the post-processing of SPECT
images.
AB - Iterative reconstruction from single photon emission computed tomography (SPECT)
data requires regularization to avoid noise amplification and edge artefacts in
the reconstructed image. This is often accomplished by stopping the iteration
process at a relatively low number of iterations or by post-filtering the
reconstructed image. The aim of this paper is to develop a method to
automatically select an optimal combination of stopping iteration number and
filters for a particular imaging situation. To this end different error measures
between the distribution of a phantom and a corresponding filtered SPECT image
are minimized for different iteration numbers. As a study example, simulated data
representing a brain study are used. For post-reconstruction filtering, the
performance of 3D linear diffusion (Gaussian filtering) and edge preserving 3D
nonlinear diffusion (Catte scheme) is investigated. For reconstruction methods
which model the image formation process accurately, error measures between the
phantom and the filtered reconstruction are significantly reduced by performing a
high number of iterations followed by optimal filtering compared with stopping
the iterative process early. Furthermore, this error reduction can be obtained
over a wide range of iteration numbers. Only a negligibly small additional
reduction of the errors is obtained by including spatial variance in the filter
kernel. Compared with Gaussian filtering, Catte diffusion can further reduce the
error in some cases. For the examples considered, using accurate image formation
models during iterative reconstruction is far more important than the choice of
the filter.
PMID- 9651036
TI - Electrical impedance tomography with compensation for electrode positioning
variations.
AB - Ideally electrical impedance tomography (EIT) should not be oversensitive to
electrode positions, but this conflicts with efforts to produce high-resolution
images. Two procedures are presented that balance reducing the sensitivity to
electrode position errors with generating practicable EIT images. The first
provides a criterion based on electrode sensitivity for regularizing the
reconstruction through spectral expansion. The main consequences of this are that
smoother images are produced and the number of artefacts and their magnitude are
generally reduced. The second modification uses the recorded data to compensate
for electrode movements that have occurred after the reference data were
measured. Image smoothness is used as the criterion for the readjustment.
Computer simulation tests have shown that this modification produces improved
image fidelity.
PMID- 9651037
TI - Site-specific confocal fluorescence imaging of biological microstructures in a
turbid medium.
AB - Normally transparent biological structures in a turbid medium are imaged using a
laser confocal microscope and multiwavelength site-specific fluorescence
labelling. The spatial filtering capability of the detector pinhole in the
confocal microscope limits the number of scattered fluorescent photons that reach
the photodetector. Simultaneous application of different fluorescent markers on
the same sample site minimizes photobleaching by reducing the excitation time for
each marker. A high-contrast grey-level image is also produced by summing
confocal images of the same site taken at different fluorescence wavelengths.
Monte Carlo simulations are performed to obtain the quantitative behaviour of
confocal fluorescence imaging in turbid media. Confocal images of the following
samples were also obtained: (i) 15 microm diameter fluorescent spheres placed
1.16 mm deep beneath an aqueous suspension of 0.0823 microm diameter polystyrene
latex spheres, and (ii) hindbrain of a whole-mount mouse embryo (age 10 days)
that was stained to fluoresce at 515 nm and 580 nm peak wavelengths. Expression
of RNA transcripts of a gene within the embryo hindbrain was detected by a
fluorescence-based whole-mount in situ hybridization procedure that we recently
tested.
PMID- 9651038
TI - A two-compartment phantom for VOI profile measurements in small-bore 31P MR
spectroscopy.
AB - A two-compartment gel phantom for VOI profile measurements in volume-selective
31P spectroscopy in small-bore units is presented. The phantom is cylindrical
with two compartments divided by a very thin (30 microm) polyethene film. This
thin film permits measurements with a minimum of susceptibility influences from
the partition wall. The phantom was used for evaluation of the volume selection
method ISIS (image-selected in vivo spectroscopy). The position of the phantom
was fixed in the magnet during the measurements, while the volume of interest
(VOI) was moved stepwise over the border. The signal from the two compartments
was measured for each position and the data were evaluated following
differentiation. We have found this phantom suitable for VOI profile measurements
of ISIS in small-bore systems. The phantom forms a useful complement to
recommended phantoms for small bore-spectroscopy.
PMID- 9651039
TI - Determination of the wavelength dependence of the differential pathlength factor
from near-infrared pulse signals.
AB - For the calculation of changes in oxyhaemoglobin, deoxyhaemoglobin and the redox
state of cytochrome-c-oxidase from attenuation data via a modified Beer-Lambert
equation the wavelength dependence of the differential pathlength factor
(DPF(lambda)) has to be taken into account. The DPF, i.e. the ratio of the mean
optical pathlength and the physical light source-detector separation at each
wavelength, determines the crosstalk between the different concentrations and is
therefore essential for a sensitive detection of chromophore changes. Here a
simple method is suggested to estimate the wavelength dependence of the
DPF(lambda) from pulse-induced attenuation changes measured on the head of adult
humans. The essence is that the DPF is the ratio of the attenuation changes over
absorption coefficient changes, and that the spectral form of the pulse
correlated absorption coefficient change can be assumed to be proportional to the
extinction coefficient of blood. Indicators for the validity of the DPF(lambda)
derived for wavelengths between 700 and 970 nm are the stability of the
calculated haemoglobin and cytochrome signals with variations of the wavelength
range included for their calculation and its overall agreement with the data
available from the literature.
PMID- 9651041
TI - Characteristics of a commercially available film digitizer and their significance
for film dosimetry.
AB - Dosimetric detectors used in high-energy photon radiation dosimetry mainly
perform a zero- or one-dimensional measurement. These low-dimensional methods are
not always adequate in the context of conformal radiotherapy. Therefore, two
dimensional film dosimetry has attracted attention. We studied a 12-bit CCD-based
film digitizer (Vidar VXR-12) with regard to accurate film dosimetry. We
investigated the stability, linearity, noise, effects of aberrant light scatter
and built-in conversion tables. A digitizing resolution of 75 dpi and a
digitizing speed of 20 ms/line result in an optimal signal-to-noise ratio. At
optical densities above 2.0, the reading accuracy of the digitizer is limited by
noise. The results of various experiments prove both the capabilities and
limitations of the digitizer studied. We also propose a method to acquire and
process film data using such a digitizer.
PMID- 9651040
TI - Application of the Monte Carlo integration (MCI) method for calculation of the
anisotropy of 192Ir brachytherapy sources.
AB - Source anisotropy is a very important factor in the brachytherapy quality
assurance of high-dose rate (HDR) 192Ir afterloading stepping sources. If
anisotropy is not taken into account then doses received by a brachytherapy
patient in certain directions can be in error by a clinically significant amount.
Experimental measurements of anisotropy are very labour intensive. We have shown
that within acceptable limits of accuracy, Monte Carlo integration (MCI) of a
modified Sievert integral (3D generalization) can provide the necessary data
within a much shorter time scale than can experiments. Hence MCI can be used for
routine quality assurance schedules whenever a new design of HDR or PDR 192Ir is
used for brachytherapy afterloading. Our MCI calculation results are compared
with published experimental data and Monte Carlo simulation data for
microSelectron and VariSource 192Ir sources. We have shown not only that MCI
offers advantages over alternative numerical integration methods, but also that
treating filtration coefficients as radial distance-dependent functions improves
Sievert integral accuracy at low energies. This paper also provides anisotropy
data for three new 192Ir sources, one for the microSelectron-HDR and two for the
microSelectron-PDR, for which data are currently not available. The information
we have obtained in this study can be incorporated into clinical practice.
PMID- 9651042
TI - Photon dose calculations in homogeneous media for a treatment planning system
using a collapsed cone superposition convolution algorithm.
AB - This work reports on some of the initial tests that were conducted during the
commissioning of a commercially available 3D treatment planning system. The
system (Pinnacle 3.0d-u1) uses a collapsed cone implementation of the
superposition convolution algorithm. Calculated and measured dose in homogeneous
media were compared for wedged and unwedged fields for both symmetric and
asymmetric collimator settings. Results show agreement of 2% or 2 mm in most
cases. Where larger differences were found, further investigation was undertaken
to explain these differences. These tests demonstrate the correct behaviour of
the collapsed cone implementation of the algorithm in homogeneous media and its
ability to characterize the beam.
PMID- 9651043
TI - The FEMA GRAS assessment of lactones used as a flavour ingredients. The Flavor
and Extract Manufacturers' Association. Generally recognized as safe.
PMID- 9651044
TI - Heterocyclic amine content in beef cooked by different methods to varying degrees
of doneness and gravy made from meat drippings.
AB - Meats cooked at high temperatures sometimes contain heterocyclic amines (HCAs)
that are known mutagens and animal carcinogens, but their carcinogenic potential
in humans has not been established. To investigate the association between HCAs
and cancer, sources of exposure to these compounds need to be determined. Beef is
the most frequently consumed meat in the United States and for this study we
determined HCA values in beef samples cooked in ways to represent US cooking
practices, the results of which can be used in epidemiological studies to
estimate HCA exposure from dietary questionnaires. We measured five HCAs [2-amino
3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
(MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8
trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6
phenylimidazo[4,5-b]pyridine (PhIP)] in different types of cooked beef using
solid-phase extraction and HPLC. Steak and hamburger patties were pan-fried, oven
broiled, and grilled/barbecued to four levels of doneness (rare, medium, well
done or very well done), while beef roasts were oven cooked to three levels of
doneness (rare, medium or well done). The measured values of the specific HCAs
varied with the cut of beef, cooking method, and doneness level. In general,
MeIQx content increased with doneness under each cooking condition for steak and
hamburger patties, up to 8.2 ng/g. PhIP was the predominant HCA produced in steak
(1.9 to 30 ng/g), but was formed only in very well done fried or grilled
hamburger. DiMeIQx was found in trace levels in pan-fried steaks only, while IQ
and MeIQ were not detectable in any of the samples. Roast beef did not contain
any of the HCAs, but the gravy made from the drippings from well done roasts had
2 ng/g of PhIP and 7 ng/g of MeIQx. Epidemiological studies need to consider the
type of meat, cooking method and degree of doneness/surface browning in survey
questions to adequately assess an individual's exposure to HCAs.
PMID- 9651045
TI - Heterocyclic amine content of pork products cooked by different methods and to
varying degrees of doneness.
AB - Heterocyclic amines (HCAs) are known mutagens and animal carcinogens produced in
meats cooked at high temperature. As pork is the second most frequently consumed
meat in the United States, five predominant HCAs [2-amino-3-methylimidazo[4,5
f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8
dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4.5
f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
(PhIP)] were measured in various pork products, cooked by different techniques
and to varying doneness levels. Pork chops and ham slices were pan-fried and oven
broiled; bacon was pan-fried, oven-broiled or microwaved; hot dogs were pan
fried, oven-broiled, grilled/barbecued or boiled; sausage links and patties were
pan-fried. All the products were cooked to three levels of doneness: just until
done, well done or very well done. HCA type and level varied substantially by
pork product, cooking method and doneness level. The highest PhIP levels were
found in well done and very well done oven-broiled bacon; for very well done 30.3
and 4.0 ng per gram of meat of PhIP and MeIQx, respectively. Pan-fried very well
done sausage patties contained 5.4 ng of MeIQx per gram of meat, while sausage
links contained 1.3 ng per gram of meat. MeIQx was formed in well done and very
well done pan-fried but not broiled pork chops. Hot dogs or ham slices had low or
undetectable levels of HCAs. These results demonstrate that epidemiological
studies investigating the relationship between HCA intake and cancer risk need to
incorporate type of meat, cooking method and degree of doneness/surface browning
into questions to assess adequately an individual's HCA exposure.
PMID- 9651046
TI - Variation in susceptibility to the induction of forestomach tumours by butylated
hydroxyanisole among rats of different strains.
AB - The forestomach carcinogenicity of butylated hydroxyanisole (BHA) was compared in
males of the F344, SHR, Lewis and Sprague Dawley rat strains. Groups of 30 6-wk
old animals were given a pellet diet containing 2% BHA for 104 wk. Forestomach
squamous cell papillomas and hyperplasias developed in all rats given BHA,
independent of the strain, but the incidences of squamous cell carcinomas (SCCs)
differed considerably: F344, 26.7% (8/30) SHR, 76.7% (23/30) SD, 36.7% (1130)
Lewis, 6.7% (2/30). Cytotoxic effects, reflected by inflammation, were also most
severe in the SHR strain, correlating well with the development of SCCs. The
present results indicate that major strain differences exist regarding BHA rat
forestomach carcinogenesis and that sensitivity to cytotoxicity might be an
important parameter.
PMID- 9651047
TI - Identification of 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 4-hydroxy-2(or
5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF) with DNA breaking activity in soy
sauce.
AB - Components with DNA breaking activity in soy sauce were investigated. It was
found that there were water soluble high molecular weight DNA breaking components
in soy sauce. Two DNA breaking components in the ethyl acetate extract of soy
sauce were identified as fragrant components, 2,5-dimethyl-4-hydroxy-3(2H)
furanone (DMHF) and 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF),
in addition to the previously characterized DNA breaking fragrant component 4
hydroxy-5-methyl-3(2H)-furanone (HMF) (Hiramoto et al., 1996b). Characterization
of DNA breaking activity of HEMF was performed, and the mechanisms for the
breaking were considered. HEMF cleaved the single strands of supercoiled pBR 322
DNA at pH 7.4 dose dependently and time dependently. DNA breaking was inhibited
by superoxide dismutase, catalase, hydroxyl radical scavengers, spin trapping
agents and metal chelators, and enhanced by Fe(III) ion. Electron spin resonance
spin trapping technique revealed the generation of hydroxyl radical. Hence,
active oxygen species derived from interaction of HEMF with metal ions and oxygen
participated in the cleavage. HEMF exhibited mutagenicity to Salmonella
typhimurium TA100 without metabolic activation and induced micronucleated mouse
peripheral reticulocytes.
PMID- 9651048
TI - Effect of baking and freeze-drying on the direct and indirect mutagenicity of
extracts from the edible mushroom Agaricus bisporus.
AB - The objectives of the study were to evaluate the effect of baking and freeze
drying on the direct and indirect mutagenicity in the Ames test of ethanolic
extracts from the edible mushroom Agaricus bisporus. Direct mutagenicity was not
influenced by baking for 10 min at 225 degrees C, but more prolonged baking, for
example 4 hr at 100 degrees C reduced mutagenicity. Hepatic cytosol from Aroclor
1254-induced rats and mushroom tyrosinase potentiated the mutagenic response
elicited by the mushroom extracts. Baking did not influence either of these
processes. Finally, freeze-drying influenced neither the direct nor the indirect
mutagenicity of the mushroom extracts. It is concluded that mutagenic and
premutagenic compounds present in mushroom are generally not heat labile.
PMID- 9651049
TI - Ability of dairy strains of lactic acid bacteria to bind a common food
carcinogen, aflatoxin B1.
AB - This study was conducted to examine the ability of selected dairy strains of
lactic acid bacteria to remove aflatoxin B1 (AFB1) from liquid media. Both
Lactobacillus rhamnosus strain GG (LBGG) and L. rhamnosus strain LC-705 (LC705)
can significantly (P > 0.05) remove AFB1 when compared with that by other strains
of either Gram-positive or Gram-negative bacteria. Removal of AFB1 by LBGG and
LC705 was a rapid process with approximately 80% AFB1 removed at 0 hr. Removal of
AFB1 by these two strains was both temperature and bacterial concentration
dependent.
PMID- 9651050
TI - Strategies for identifying false positive responses in predictive skin
sensitization tests.
AB - It is important that predictive toxicological test methods are selective for
their intended endpoint and that their limitations are understood and
acknowledged. The local lymph node assay (LLNA) is a relatively new predictive
test for skin sensitization potential that can replace traditional guinea pig
tests and offers significant scientific and animal welfare advantages. However,
there has been some concern that certain irritant materials may yield false
positive results, although it must be emphasized that false positives also occur
in guinea pig methods. Consequently, we have examined the performance in the LLNA
of a range of skin irritants, from varying chemical classes and covering a range
of irritation potency. The results presented here demonstrate clearly that the
majority of skin irritants are negative in the LLNA. These results are reviewed
in the context of the occurrence of false positive reactions in the guinea pig
maximization test and the strategies for dealing with such results are discussed.
The need for careful scientific evaluation of the results in all predictive tests
for sensitization is thus emphasized. In terms of specificity, the LLNA has been
more fully evaluated than other predictive test methods and is at least as
accurate. In terms of animal welfare, objectivity, reproducibility and
reliability it is superior to other methods. In summary, all predictive skin
sensitization test results should be evaluated in a scientifically rigorous
manner and the additional data provided herein further support the adoption of
the LLNA as a complete replacement for the traditional guinea pig methods.
PMID- 9651051
TI - Biochemistry and toxicology of the diterpenoid glycoside atractyloside.
AB - Atractyloside (Atr) is a diterpenoid glycoside that occurs naturally in plants
(many of which are used in ethnomedicines) found in Europe, Africa, South
America, Asia and the far East. It is also present in animal grazing forage. Atr
(and its analogues) may be present at levels as high as 600 mg/kg dried plant
material. Consumption of the plants containing Atr or carboxyatractyloside
(carboxyAtr) has caused fatal renal proximal tubule necrosis and/or centrilobular
hepatic necrosis in man and farm animals. Although pure Atr and crude plant
extracts disrupt carbohydrate homeostasis and induce similar pathophysiological
lesions in the kidney and liver, it is also possible that the toxicity of Atr may
be confounded by the presence of other natural constituents in plants. Atr
competitively inhibits the adenine nucleoside carrier in isolated mitochondria
and thus blocks oxidative phosphorylation. This has been assumed to explain
changes in carbohydrate metabolism and the toxic effects in liver and kidney.
Although the acute toxicity of Atr is well described, many aspects of Atr
toxicity (subchronic and chronic toxicity, reproductive toxicity, mutagenicity
and carcinogenicity) have not been investigated and pharmacokinetic and
metabolism data are limited. In vitro proximal tubular cells are selectively
sensitive to Atr, whereas other renal cell types are quite resistant. There are
also differences in the response of liver and renal tissue to Atr. Thus, not all
of the clinical, biochemical and morphological changes caused by Atr can simply
be explained on the basis of inhibition of mitochondrial phosphorylation. The
relevance to a wider human risk is shown by the presence of Atr analogues in
dried roasted Coffea arabica beans (17.5 32 mg/kg). There are no data to help
identify the risk of low dose chronic exposure in human coffee consumers, nor is
there information on the levels of Atr or its analogues in other commonly
consumed human foodstuffs.
PMID- 9651052
TI - Review of the biological properties and toxicity of bee propolis (propolis).
AB - Propolis is a multifunctional material used by bees in the construction and
maintenance of their hives. Use of propolis by humans has a long history,
predated only by the discovery of honey. Use of products containing propolis have
resulted in extensive dermal contact and it is now increasingly being used a
dietary supplement. Unlike many 'natural' remedies, there is a substantive
database on the biological activity and toxicity of propolis indicating it may
have many antibiotic, antifungal, antiviral and antitumour properties, among
other attributes. Although reports of allergic reactions are not uncommon,
propolis is relatively non-toxic, with a no-effect level (NOEL) in a 90-mouse
study of 1400 mg/kg body weight/day.
PMID- 9651053
TI - The role of the radiologist in breast diagnosis: a surgeon's personal view.
PMID- 9651054
TI - Pulmonary arteriovenous malformations.
AB - Pulmonary arteriovenous malformations (PAVMs) are uncommon lesions, but are the
cause of considerable morbidity and occasional mortality. They most commonly
occur in association with hereditary haemorrhagic telangectasia and screening of
families with this condition is therefore important. Embolization of PAVMs by
coils is a well tolerated effective procedure with a low complication rate in
skilled hands. Treatment results in both symptomatic and physiological
improvement, and evidence for a reduction in stroke and cerebral abscess is
accumulating. Radiological techniques now represent the primary treatment of
choice, with surgical resection rarely required.
PMID- 9651055
TI - Radiology of the jugular foramen.
AB - The jugular foramen, a complex bony canal, transmits vessels and nerves from the
posterior cranial fossa through the skull base into the carotid space. It is
inaccessible to clinical examination and radiology plays a central role in
evaluating this region. Familiarity with the normal anatomy of this area will
help in the formulation of differential diagnosis and the assessment of disease
extent. Both intracranial and extracranial lesions may affect the jugular foramen
in addition to intrinsic abnormalities. Normal variants and artefacts seen on
magnetic resonance imaging (MRI) should not be mistaken for pathological
processes.
PMID- 9651056
TI - CT appearances and prognostic significance of splenic metastasis in ovarian
cancer.
AB - DESIGN: A retrospective review of women undergoing computed tomography (CT) as
part of the investigation and management of pathologically proven ovarian cancer
in a single specialist gynaecological cancer centre. OBJECTIVE: To ascertain CT
appearances and prognostic significance of splenic involvement in ovarian cancer.
RESULTS: We found a 10.3% frequency of splenic metastasis in a series of 321
patients with ovarian cancer. Thirty-three women had splenic metastases
demonstrated on CT. Twenty-three women had surface lesions with an irregular
scalloped shape and broad contact with the splenic surface; 17 of these women had
lesions at presentation. Ten women had parenchymal lesions, five at presentation
and five at relapse, typically with a rounded shape surrounded by normal splenic
tissue. Four out of 10 cases with parenchymal involvement showed lesion
progression during chemotherapy. However, lesion progression occurred in only one
of 23 cases with surface disease (P < 0.025, Fisher's exact test). In 16 cases
with disease involving both spleen and liver, the response to chemotherapy was
the same in both organs. CONCLUSION: We have found a higher frequency of splenic
metastasis from ovarian cancer during life than previously reported. Parenchymal
lesions are significantly less likely to respond to treatment than surface
lesions but are more commonly a feature of relapsed disease. We have demonstrated
that splenic metastases behave similarly to liver metastases in ovarian cancer.
We suggest that the presence of splenic parenchymal metastasis is indicative of
FIGO stage IV disease. This finding has implications for proposed cytoreductive
surgery.
PMID- 9651057
TI - Correlation of CT with histopathological findings in patients with gastric and
gastro-oesophageal carcinomas following neoadjuvant chemotherapy.
AB - Gastric carcinoma is the fourth commonest cause of death from malignant disease
in United Kingdom. In the Western hemisphere, it usually presents with advanced
disease, which contributes to its very poor prognosis. Pre-operative
(neoadjuvant) chemotherapy offers the possibility of down-staging such tumours
and the potential to render tumours operable. Computed tomography (CT) plays a
central role in the assessment of patients presenting with the disease, and in
those who undergo chemotherapy, in evaluating their response. OBJECTIVE: This
study was undertaken to evaluate the role of CT in predicting loco-regional
spread of tumour following neoadjuvant chemotherapy in non-metastatic gastric and
gastro-oesophageal cancers. METHODS AND MATERIALS: We correlated CT evidence of
loco-regional spread with pathological findings following surgery in 21 patients
who received pre-operative chemotherapy. RESULTS: Residual masses were seen on CT
in 19 patients, and 15 contained active tumour, although in four patients no
viable tumour was demonstrated at histopathology. The overall accuracy of CT in
assessing loco-regional disease was disappointing with sensitivities,
specificities, positive and negative predictive values of 57%, 43%, 75% and 33%,
respectively. CONCLUSIONS: We conclude that CT is not accurate in identifying
residual loco-regional spread and therefore should not preclude surgery in those
patients who have received neoadjuvant chemotherapy.
PMID- 9651058
TI - Characterization of primary intracranial lymphoma by computed tomography: an
analysis of 36 cases and a review of the literature with particular reference to
calcification haemorrhage and cyst formation.
AB - Previous published series describing the appearances of primary central nervous
system lymphoma (PCNSL) state that calcification, haemorrhage and cyst formation
are rare, but generally fail to quantify or expand on this statement. We present
the pre-treatment computed tomography (CT) findings of 36 patients with biopsy
proven PCNSL. In this series, calcification was present in only one very atypical
lesion and evidence of haemorrhage was not seen. Small intralesional cysts were
present in four of the total of 50 lesions. PCNSL usually appeared as one or more
well defined focal lesions, iso- or hyperdense to grey matter, with homogeneous
enhancement following IV contrast injection. Less commonly the contrast
enhancement was inhomogeneous, only one lesion failed to enhance.
Disproportionately little oedema and mass effect compared with lesion size was
noted on approximately half the CTs. Lesions usually touch either the ependymal
lining of the ventricles or the leptomeningeal surface.
PMID- 9651059
TI - Mediastinal lymphadenopathy in cryptogenic fibrosing alveolitis: the effect of
steroid therapy on the prevalence of nodal enlargement.
AB - PURPOSE: To determine the prevalence of enlarged mediastinal lymph nodes in
cryptogenic fibrosing alveolitis (CFA) and to assess whether this frequency was
related to steroid administration. MATERIAL AND METHODS: Retrospective review of
chest radiographs and high-resolution computed tomography (CT) of 54 patients
with proven cryptogenic fibrosing alveolitis (CFA). Twenty-two of the 54 patients
received oral steroids up to 2 months before the time of high-resolution CT
examination (group 1); the remaining 32 patients had not taken steroids for at
least 6 months before study entry (group 2). The prevalence, distribution, and
size of enlarged mediastinal lymph nodes was determined in all groups. The
diagnosis of CFA was histologically established in 44 patients. In 10 patients
the diagnosis of CFA was based on clinical and high-resolution CT findings.
RESULTS: Mediastinal lymphadenopathy was present in 26 of 54 patients with CFA.
The prevalence of enlarged nodes was 14% (three of 22) in patients who had
received oral steroids up to 2 months before the time of CT examination, and 71%
(23 of 32) in patients that had not taken steroids for at least 6 months before
study entry. CONCLUSION: We conclude that patients with CFA on steroid therapy
had a significantly lower prevalence of mediastinal adenopathy (P < 0.001) than
patients who had not taken steroids.
PMID- 9651060
TI - The effect of angiographic technique and image quality on the reproducibility of
measurement of carotid stenosis and assessment of plaque surface morphology.
AB - We studied the reproducibility of measurement of carotid stenosis and assessment
of plaque surface morphology on 1001 angiograms from a consecutive series of
patients entered into the European Carotid Surgery Trial. Inter-observer
agreement (Kappa statistic, 95% confidence interval (CI)) for categorization of
carotid stenosis, as 0-29%, 30-69% or 70-99% was good (0.68, 0.63-0.73) on 789
conventional or digitally subtracted selective angiograms, and good (0.64, 0.54
0.75) on 174 conventionally and digitally subtracted aortic arch injection
angiograms, but was poor (0.29, 0.02-0.80) on 29 intravenous digital subtraction
angiograms. Inter-observer agreement did not vary with the method of image
acquisition of arterial angiograms, but was dependent on the quality of
visualization of the stenosis: kappa = 0.73 (0.67-0.79) for good quality
angiograms vs. 0.54 (0.44-0.64) for poor quality angiograms. Inter-observer
agreement for assessment of plaque surface morphology was moderate (kappa 0.4
0.6) and did not vary with type of angiography or method of image acquisition.
However, ulceration was reported most frequently on selective angiograms and on
those angiograms on which the quality of visualization of the stenosis was good.
We conclude that the reproducibility of measurement of carotid stenosis and the
assessment of plaque surface morphology vary depending on the type of angiography
and the quality of visualization of the stenosis. This should be taken into
account when validating non-invasive methods of imaging the carotid bifurcation.
PMID- 9651061
TI - Technical report: Combined carotid bifurcation endarterectomy and intra-operative
transluminal angioplasty of a proximal common carotid artery stenosis: an
alternative to extrathoracic bypass.
AB - A method of management of a dual stenoses affecting the proximal common carotid
artery and the internal carotid artery, the tandem lesion, is described in two
cases. The combination of a surgical endarterectomy of the internal carotid
artery narrowing and percutaneous balloon dilatation of the more proximal common
carotid artery narrowing, via the arteriotomy site, with clamping of the internal
carotid artery was successfully employed to avoid an extrathoracic bypass
procedure.
PMID- 9651062
TI - Imaging of the portal vein during transjugular intrahepatic portosystemic shunt
procedures: a comparison of carbon dioxide and iodinated contrast.
AB - We report our experience with wedged hepatic injections of carbon dioxide (CO2)
in the imaging of the portal vein during transjugular intrahepatic portosystemic
shunt (TIPS) procedures. In all patients CO2 allowed quick and effective
visualization of the portal vein. The image quality and extent of visualization
of the portal vein was considered superior to iodinated contrast media in all
cases. We suggest that CO2 should be used more frequently during TIPS.
PMID- 9651063
TI - Gallstone ileus: CT findings.
AB - We describe the CT findings of four consecutive cases of surgically proven
gallstone ileus and discuss the pathophysiology of gallstone ileus and the impact
of CT on diagnosis of the condition.
PMID- 9651064
TI - Case report: Transcatheter embolization of a superior mesenteric artery
pseudoaneurysm with interlocking detachable coils.
PMID- 9651065
TI - Case report: Urinary bladder rhabdomyosarcoma associated with Beckwith-Wiedemann
syndrome.
PMID- 9651066
TI - Case report: Portal venous thrombosis in acute cholecystitis. CT, ultrasound,
Doppler and power Doppler findings.
PMID- 9651067
TI - Case report: Use of an IVC filter in the management of IVC thrombosis occurring
as a complication of acute pancreatitis.
PMID- 9651068
TI - Diabetics on Metformin.
PMID- 9651069
TI - Ocular ultrasound.
PMID- 9651070
TI - Solitary cystic nodal metastasis occult papillary carcinoma of the thyroid
mimicking a branchial cyst--a potential pitfall.
PMID- 9651071
TI - Corticosteroids--a case of mistaken identity?
PMID- 9651072
TI - Skin and joint disease in psoriatic arthritis: what is the link?
PMID- 9651073
TI - Monoclonal antibody therapy in rheumatoid arthritis.
AB - Monoclonal antibodies bind to their targets with high specificity and therefore
have excellent potential as therapeutic agents. Biotechnological advances have
allowed the production of large quantities of engineered monoclonal antibodies
for therapeutic use. Recent research in rheumatoid arthritis has identified
important mediators of synovitis. Monoclonal antibodies targeting these have been
tested in clinical trials over the last decade. Anti-cytokine therapies, in
particular anti-tumour necrosis factor alpha monoclonal antibodies, suppressed
inflammation and produced rapid symptomatic improvement. Anti-lymphocyte
monoclonal antibodies produced long-lasting disease suppression in animal models
of rheumatoid arthritis. The use of depleting anti-lymphocyte monoclonal
antibodies in rheumatoid arthritis had been disappointing as they did not
penetrate the synovial joint in sufficient quantity to suppress disease without
producing severe and protracted peripheral blood lymphopenia. Consequently, their
use in rheumatoid arthritis had been abandoned. In contrast, clinical trials of
non-depleting anti-CD4 monoclonal antibodies in rheumatoid arthritis showed that
they could suppress synovitis. However, it remains unclear whether they could
lead to prolonged disease improvement.
PMID- 9651074
TI - Prevalence of the major rheumatic disorders in the adult population of north
Pakistan.
AB - The prevalence of rheumatic diseases in developing countries is largely unknown.
Studies which allow comparison of data within the contrasting communities of the
Third World and the developed world have the potential to provide insights into
disease aetiologies. The current study compared the frequency of rheumatic
symptoms (point prevalence) amongst 1997 adults distributed evenly between poor
rural and poor urban communities and relatively affluent urban people.
Comparisons were also made with similarly but previously derived prevalence rates
of rheumatic symptoms and rheumatoid arthritis (RA) in south Pakistan and
Pakistanis in England. A significantly higher prevalence of joint pain was seen
in the north compared with the south. RA was more common in the north and similar
to the frequency amongst Pakistanis resident in England. Ethnic and genetic
susceptibility might have accounted for this. There was significantly more soft
tissue rheumatism and back pain in the northern rural population compared with
those in the city. Fibromyalgia was almost completely absent from the urban
affluent, but osteoarthritis of the knee was significantly more common in this
community, perhaps due to relative obesity. RA was least in the urban poor, a
phenomenon that might be attributable to earlier death of females or other
undetermined factors.
PMID- 9651075
TI - Clinical evaluation of spine morphometric X-ray absorptiometry.
AB - A new method for vertebral height measurements, morphometric X-ray absorptiometry
(MXA) based on dual-energy X-ray absorptiometry, has been proposed. This
technique overcomes some limitations of morphometric radiography (MRX): the
effective radiation dose is low, some sources of geometric distortion are
eliminated, such as dependence on patient position, magnification gradient, and
the effect of scoliosis is minimized. The purpose of this study was to compare
morphometric parameters obtained by both methods (MXA and MRX), and to evaluate
the agreement between morphometric evaluations and qualitative reading for
vertebral fracture diagnosis. The evaluation was performed with an Hologic QDR
2000 device in 67 women without vertebral fractures and 31 women with vertebral
fractures (according to a qualitative assessment). The reproducibility of the
image analysis was <4% and comparable to MRX. The estimated bias between the two
methods was on average 10 mm, and was a function of the vertebral height,
according to the Bland and Altman method. The agreement between MXA and other
methods for vertebral fracture diagnosis was poor for the thoracic level above
T7, due to a lack of resolution and rib interposition. Agreement was also low for
T10, due to the motion of the diaphragm muscle. MXA cannot currently be used for
the diagnosis of thoracic vertebral fracture in clinical practice. Technological
improvements are necessary to make this promising method useful as a screening
tool to evaluate the presence of thoracic vertebral fractures.
PMID- 9651076
TI - Methotrexate reduces inflammatory cell numbers, expression of monokines and of
adhesion molecules in synovial tissue of patients with rheumatoid arthritis.
AB - Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of
rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic
effect has not yet been defined. The aim of the present study was to investigate
the effect of MTX treatment (7.5-15 mg/week) on synovial tissue in RA. For this
purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks
after initiation of MTX therapy. Immunohistochemistry was performed using
monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68,
MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)-1alpha, IL-1beta,
tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All
parameters for disease activity improved during the period of treatment.
Immunohistochemical analysis revealed a statistically significant decrease in
scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion
molecules E-selectin and VCAM-1. The observed decrease in synovial scores for
inflammatory cells, monokines and adhesion molecules suggests that the anti
inflammatory effect of MTX is, in part, dependent on a reduction in monokine
inducible vascular adhesion molecules and subsequent reduction of cell traffic
into joints.
PMID- 9651077
TI - The short-term health outcome of out-patient rheumatology consultations in
relation to rationing: a pilot study.
AB - The objectives were to test whether the short-term health outcome of rheumatology
out-patients differs according to clinical priority. The setting was an NHS
regional rheumatology out-patient department serving a catchment population of
over 1 million. The subjects were 249 consecutive rheumatology out-patients
categorized on the basis of the referral letter as 'urgent' (n = 50), 'soon' (n =
100) or 'routine' (n = 99). Primary outcome measures were the proportion of
patients reporting improvement in health categorized by clinical priority
(urgent, soon or routine) or main diagnostic group (inflammatory or non
inflammatory disease). Secondary outcome was change in health status measured
using the EuroQol generic health instrument (EQ-5D). Small but insignificant
differences in the proportion of patients reporting health improvement were found
between the urgent (28%), soon (23%) and routine (17%) categories (Kruskal
Wallis, P = 0.186). Thirty per cent of patients with inflammatory joint disease
reported improvement compared with 17% of those with non-inflammatory conditions
(Mann-Whitney U, P = 0.019). In patients reporting improvement, the median
(interquartile range) improvement in EQ-5D health utility score was +0.2 (0.58)
(P = 0.0001) and that of visual analogue health score was +5 (16) (P = 0.001).
Clinical priority setting, by giving priority to some patients over others,
results in rationing by delay. These data do not support the hypothesis that
fewer patients given a low clinical priority gain health benefit compared with
those given a high priority. However, those with inflammatory joint disease do
appear to have better short-term health outcomes.
PMID- 9651078
TI - Body composition in systemic lupus erythematosus.
AB - The objectives were to determine the body composition, and the effects of disease
and corticosteroid therapy on body composition, in a population of female
patients with systemic lupus erythematosus (SLE). All female SLE patients managed
through a single centre were invited to participate in a cross-sectional study of
body composition. Data were collected by standardized interview and examination,
and review of medical records. Body composition was assessed by dual-energy X-ray
absorptiometry (DXA). Eighty-two subjects were evaluated, 30 of whom were post
menopausal. Univariate linear regression analysis revealed a significant
association of reduced fat-free mass with SLE severity [as measured by the
Systemic Lupus International Collaborative Clinics (SLICC)] (P = 0.020), a
history of corticosteroid exposure (P = 0.043) and age (P = 0.048). Reduced total
body bone mineral density (BMD) was also significantly associated with SLICC (P <
0.001) and corticosteroid exposure (P = 0.017), and with age (P < 0.001), post
menopausal status (P = 0.003) and the duration of menopause (P < 0.001). Stepwise
multiple linear regression analysis revealed a significant association between
fat-free mass and total body, lumbar spine and femoral neck BMD (P = 0.007, P =
0.025, P = 0.003, respectively). Fat mass was significantly associated only with
lumbar spine BMD (P = 0.008). In this SLE population, disease severity and
corticosteroid exposure were independently associated with a negative effect both
on total body BMD and on fat-free mass. Fat-free mass was a significant predictor
of lumbar spine, femoral neck and total body BMD.
PMID- 9651079
TI - Bacteria-specific lymphocyte proliferation in peripheral blood in reactive
arthritis and related diseases.
AB - The cellular immune response seems to be important for the pathogenesis of
reactive arthritis (ReA) and a bacteria-specific lymphocyte proliferation (LP) is
often found in synovial fluid (SF) of ReA patients. However, the role of the
bacteria-specific LP in peripheral blood (PB) is less well defined. In this
study, we investigated 215 paired samples of SF and PB from patients with ReA (n
= 65), undifferentiated oligoarthritis (n = 133) and undifferentiated
spondylarthropathy (n = 17) to analyse the LP in PB and SF in relation to time.
In 24 out of 87 patients (27.6%) with a bacteria-specific LP in synovial fluid, a
positive LP to the same bacterium was also found in PB. While a positive LP in SF
was found most frequently in the first week of the arthritis, a positive LP in PB
was detected in 45% of patients when investigated between weeks 2 and 4 after the
onset of arthritis, but was rarely found very early and late in the course of the
arthritis. The time point seems to be crucial for the investigation of an LP in
PB in patients with ReA.
PMID- 9651080
TI - Characterization of the humoral immune response to Klebsiella species in
inflammatory bowel disease and ankylosing spondylitis.
AB - This study was carried out to characterize the antibody class response by ELISA
to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in
five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients,
46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC),
50 patients with active anti-endomysial antibody-positive coeliac disease and 40
healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody
levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2,
K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal
controls. Furthermore, IgG antibody levels were significantly elevated in CD
patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50;
and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC
group were limited only to K17, K36 and K50. No antibody class was increased to
any of the K. pneumoniae serotypes in the coeliac disease group. The immune
responses in AS patients also involve Klebsiella bacteria having capsular
serotypes other than K26, K36 and K50. The similarity in the immune responses
between CD and AS groups suggests that many AS patients may have occult bowel
inflammation.
PMID- 9651081
TI - Joint stiffness and 'articular gelling': inhibition of the fusion of articular
surfaces by surfactant.
AB - It was proposed some years ago that, in osteoarthritis, one source of joint
stiffness arises from 'articular gelling', but, if so, why does this not occur in
the normal joint? In a preliminary experiment using agar gels, it is shown how
such fusion of gel surfaces can be inhibited by surface-active phospholipid
(SAPL)--both synthetic and human--as quantified by the shear stress needed to
cause cleavage between samples after prolonged contact. On the other hand, normal
bovine articular cartilage (BAC) does not fuse to itself, but can be made to do
so if rinsed with a powerful lipid solvent known to remove the outermost layer of
adsorbed SAPL along with the hydrophobicity so characteristic of the normal
'waxy' surface it imparts. It is then shown how the inhibition of gel fusion can
be restored by treating both bovine and human articular surfaces with exogenous
SAPL derived from human AC and with synthetic SAPL. Samples of human articular
cartilage excised from osteoarthritic hips and knees during total joint
replacement showed a 55% greater tendency to fuse together than normal BAC. This
was exacerbated by solvent rinsing and can be attributed to a deficiency in the
outermost lining of SAPL previously studied as a load-bearing boundary lubricant
capable of reducing friction and wear to the remarkably low levels observed
physiologically. Hence, joint stiffness can be attributed, in part, to a
deficiency in the lubricating layer of SAPL lining the normal articular surface
where it can inhibit articular gelling/gel fusion, possibly imparting other
desirable physiological functions. The possibility of clinical replenishment of
SAPL in the osteoarthritic joint is discussed.
PMID- 9651082
TI - Bone mineral density at distal forearm can identify patients with osteoporosis at
spine or femoral neck.
AB - Forearm bone mineral density (BMD) was investigated in women to identify
osteoporosis at the spine or femoral neck (or both) defined by WHO criteria (T
score -2.5) without requirement for fracture. BMD was measured by single-energy X
ray absorptiometry (DTX100) and by dual-energy X-ray absorptiometry (DXA) in the
lumbar spine and femoral neck in 422 subjects aged 22-90 yr. A total of 62% of
subjects with osteoporosis (at the spine, femoral neck, or both sites) were
detected with 89% specificity [receiver operating characteristics (ROC) analysis]
and included all subjects below forearm BMD 0.34 g/cm2. Conversely, above 0.419
g/cm2, only 10% of patients had osteoporosis. A total of 71.8% of women could be
assigned either to those who warranted therapy (<0.34 g/cm2) or to those who did
not (>0.419 g/cm2) with 90% certainty. Subjects with forearm BMD between 0.34 and
0.419 g/cm2, who constituted 28.2% of the total group and included 31% of
subjects with osteoporosis, had a 40% chance of having osteoporosis. This leads
to a high identification rate on subsequent DXA scanning, which is thus used
efficiently.
PMID- 9651083
TI - A case of refractory adult dermatomyositis.
PMID- 9651084
TI - The clinical management of rheumatoid arthritis and osteoarthritis: strategies
for improving clinical effectiveness.
PMID- 9651085
TI - National database of patients visiting rheumatologists in The Netherlands: the
standard diagnosis register of rheumatic diseases. A report and preliminary
analysis.
PMID- 9651086
TI - Inflammatory cytokines and cytokine antagonists in whole blood cultures of
patients with systemic juvenile chronic arthritis.
AB - In the present study, we investigated the kinetics and the activation thresholds
for the production of a number of pro-inflammatory cytokines and cytokine
antagonists in Escherichia coli lipopolysaccharide (LPS) or phytohaemagglutinin
(PHA) stimulated whole blood cultures of 13 patients with systemic juvenile
chronic arthritis (SJCA) and 10 healthy children. In unstimulated cultures, the
levels of interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF
alpha) were undetectable in both groups, suggesting that there was no spontaneous
production of these cytokines by circulating leucocytes. The activation
thresholds for the production of these cytokines, as well as the capacity for
production, did not differ significantly between patients and controls. The level
of interleukin-1 receptor antagonist (IL-1ra) in plasma of the patients was
significantly elevated, while the in vitro production of IL-1ra was essentially
normal and it did not correlate with plasma levels of IL-1ra. Supernatant levels
of soluble TNF-alpha receptor (sTNF-R) I and II were both significantly elevated
and correlated with the global activity score. In contrast, the supernatant
levels of IL-10 were reduced in both PHA- and LPS-driven cultures. Although IL-10
levels did not correlate with laboratory or clinical indices of disease activity,
the results suggest that reduced IL-10 production may play a pathogenetic role in
SJCA.
PMID- 9651087
TI - Increased serum IgD concentrations in children with Henoch-Schonlein purpura.
AB - Serum IgD concentrations were measured in 39 children with Henoch Schonlein
purpura (HSP) and 40 control children by means of radial immunodiffusion. Serum
IgG, IgA and IgM concentrations in the HSP patients were measured by
nephelometry. The geometric mean IgD concentration in children with HSP (16.7
microg/ml) was significantly higher than in control children (9.1 microg/ml;
P=0.03). Serial testing in 10 HSP patients revealed no significant change in IgD
concentrations over periods ranging from 1 to 12 months. There was no
relationship between IgD and IgA concentrations in the HSP patients. Nineteen of
the 39 HSP patients (49%) had nephritis. The mean IgD concentration in patients
with nephritis (10.7 microg/ml) did not differ from control values, but was
significantly lower than the mean IgD level in the remaining 20 patients who did
not have nephritis (25.4 microg/ml; P=0.02). These results indicate that serum
IgD levels are increased in children with HSP who did not have nephritis. IgD
concentrations in patients with nephritis were similar to levels in control
children.
PMID- 9651088
TI - Do psychosocial interventions have a role to play in paediatric rheumatology?
PMID- 9651089
TI - Juvenile chronic arthritis: diagnosis and management of tibio-talar and sub-talar
disease.
PMID- 9651090
TI - Treatment of gout after transplantation.
PMID- 9651091
TI - Antimalarial drugs in the treatment of rheumatological diseases.
PMID- 9651092
TI - Kelley-Seegmiller syndrome: a case report and review of the literature.
PMID- 9651093
TI - Sacroiliitis in an HLA B27-negative patient following giardiasis.
PMID- 9651094
TI - Nailfold capillary microscopy in patients with Raynaud's phenomenon: experience
in a district general hospital.
PMID- 9651095
TI - CD134/OX40 expression by synovial fluid CD4+ T lymphocytes in chronic synovitis.
PMID- 9651096
TI - Mseleni Joint Disease: social priorities.
PMID- 9651097
TI - Two different drug-induced pulmonary complications in a patient suffering from
rheumatoid arthritis.
PMID- 9651098
TI - Trigeminal sensory neuropathy in systemic sclerosis.
PMID- 9651099
TI - Association of antiphospholipid syndrome and chronic hepatitis C.
PMID- 9651100
TI - Ondansetron prevents refractory and severe methotrexate-induced nausea in
rheumatoid arthritis.
PMID- 9651101
TI - Three infected injections from the same organism.
PMID- 9651102
TI - Use of myoblasts in assaying the osteoinductivity of bone morphogenetic proteins.
AB - A novel, time- and BMP-saving in vitro method for the detection and quantitation
of bone morphogenetic protein (BMP) activity was developed based on the
measurable effects of BMP on rat skeletal muscle myoblasts (L6). Calcium
incorporation, stimulation of alkaline phosphatase activity and production of
osteocalcin were used as markers of bone cell metabolism and on-going
morphogenesis. The morphological change was confirmed by Chlorantine fast red and
von Kossa staining. The response of various BMPs was purity-dependent and
consistent with intramuscular implantations of the same materials. Neither TGF
beta1 nor insulin could induce the same actions. The data from this study
indicate that at least in part in vivo implantations of BMP extracts can be
replaced by in vitro measurement of osteoinductivity. Considerable saving of
time, BMP and experimental animals can be achieved using cell culture conditions
for the determination of bone-forming activity.
PMID- 9651103
TI - Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth
hormone serum levels in hypothyroid rats.
AB - We have investigated the biological effects of physiological doses of 3,5-diiodo
L-thyronine (3,5-T2) and 3,3'-diiodo-L-thyronine (3,3'-T2) (at doses from 2.5 to
10 microg/100 g BW) on serum TSH and GH levels in rats made hypothyroid by
propylthiouracil and iopanoic acid administration. In such animals deiodinase
activities were inhibited and thyroid hormones serum levels strongly reduced. The
effects of T2s were compared with those elicited by 3,5,3'-triiodo-L-thyronine
(T3) (2.5 microg/100 g BW).The serum TSH level was much greater in hypothyroid
rats than in euthyroid ones. T3 administration suppressed TSH by 88% compared to
control (i.e, the level in hypothyroid rats); it thus reached a value not
significantly different from that seen in the euthyroid rats. 3,5-T2 produced a
similar effect, suppressing the TSH level by about 75% compared to control; it
thus reached values not significantly different from those of the euthyroid and
T3-treated rats. By contrast, 3,3'-T2 had no effect on TSH, whatever the dose.
The serum GH level was much lower in hypothyroid rats than in euthyroid ones. T3
administration increased the GH level by about 5-fold, restoring it to the value
seen in euthyroid rats. 3,5-T2-treated hypothyroid rats, at all the doses used
(from 2.5 to 10 microg/100 g BW), showed increased serum GH levels: at a dose of
10 microg/100 g BW the level reached a value about 5-fold higher than that in
hypothyroid rats. This value was not significantly different from those of
euthyroid and T3-treated rats. 3,3'-T2 did not affect GH levels whatever the
dose. Thus, 3,5-T2 (but not 3,3'-T2) seems to mimic the effects of T3 on serum
TSH and GH levels in rats.
PMID- 9651104
TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and PACAP27
differentially stimulate growth hormone release and mRNA accumulation in porcine
somatotropes.
AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been suggested to
regulate growth hormone (GH) secretion in several species. Here, we analyzed the
in vitro effects of PACAP38 and PACAP27 on the secretory activity of porcine
somatotropes. Cultures of porcine pituitary cells were treated with PACAP38 and
PACAP27, and GH release, intracellular GH content, and GH mRNA levels were
evaluated. Also, the time course of changes in the somatotrope content of GH and
its mRNA in response to PACAPs were measured. Both PACAPs stimulated GH release
from porcine somatotropes in a broad range of doses (10(-10)-10(-6) M), yet only
PACAP27 elicited a dose-dependent response. GH cell content remained essentially
unchanged after PACAP treatment. In contrast, both PACAPs induced significant and
sustained increases in GH mRNA cell content, although the response to PACAP27
appeared faster (8 h) than to PACAP38 (16 h). These results demonstrate that
PACAP stimulates GH production in porcine somatotropes. Furthermore, the
differential responses induced by PACAP38 and PACAP27 suggest that distinct
mechanisms mediate their effects on this cell type.
PMID- 9651105
TI - Interaction of isatin with type-A natriuretic peptide receptor: possible
mechanism.
AB - The effect of isatin on rat brain particulate guanylate cyclase (GC) was
investigated. The enzyme was stimulated by atrial natriuretic peptide (ANP),
brain natriuretic peptide (BNP) and urodilatin, but not by C-type natriuretic
peptide (CNP). Their effects were not additive, pointing to action via the GC-A
receptor. Isatin, in dose-dependent manner, abolished this stimulation. The non
hydrolysable ATP analogue, adenylylimidodiphosphate, potentiated the effects of
submaximal doses of ANP, BNP and urodilatin on this particulate GC-A, and
attenuated or abolished sensitivity to isatin. These results suggest that isatin
antagonises the generation of second messenger by GC-A; this sensitivity might be
regulated at an ATP binding site, possibly a protein kinase-like domain.
PMID- 9651106
TI - The pharmacokinetic change of lidocaine by catecholamines using isolated perfused
rat liver (IPRL).
AB - We hypothesized that changes in the pharmacokinetics of lidocaine might reveal
changes in portal circulation induced by catecholamines. Isolated perfused rat
liver (IPRL) was selected as an experimental model, since experimental conditions
in this model could be regulated. The liver was perfused with a recirculating
system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was
administered along with one of three drugs, dopamine, norepinephrine or adenosine
triphosphate. The fractional transfer rate constants, k21 and k12, from medium to
liver and liver to medium, respectively, and ke, the elimination rate constant,
were calculated using a two-compartment model with the SAAM II program. Curves of
decay of lidocaine from the recirculating medium consisted of a fast and a slow
component. Norepinephrine and high-dose dopamine significantly increased k12,
while low-dose dopamine significantly increased k21 and ke compared with control
values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer
rate from liver to medium, while low-dose dopamine increased the transfer rate
from medium to liver and the rate of elimination from liver. These findings
suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake
and that low-dose dopamine improves uptake in IPRL.
PMID- 9651107
TI - Role of beta-adrenoceptor on renal interleukin-6 and tumor necrosis factor in
spontaneously hypertensive rats.
AB - We have shown previously in the spontaneously hypertensive rat (SHR) kidney that
interleukin-6 (IL-6) and tumor necrosis factor (TNF) mRNA levels were low under
conditions of acute anaesthesia and surgical stress. The reasons for the
suppression of IL-6 and TNF gene expression in the SHR were investigated by
examining the influence of enhanced beta-adrenergic stimulation, high blood
pressure, and renal function (renal blood flow, glomerular filtration rate,
plasma creatinine levels) on renal IL-6 and TNF mRNAs. The experiments were
performed by means of the following three studies; (1) SHR and Wistar rats at 4,
7, 9 week old were injected with lipopolysaccaride (LPS), and then a relationship
between blood pressure levels and IL-6 and TNF mRNA levels were estimated, (2)
isoproterenol and propranolol were administered into SHR and WKY rats, and the
levels of IL-6 and TNF mRNA were compared, (3) under condition of anaesthesia and
surgical stress, blood pressure and renal functions in SHR were measured, and
then the relationships between these factors and IL-6 or TNF mRNA levels were
analyzed. Renal IL-6 and TNF mRNAs in SHR remained low even though blood pressure
increased with age and there was no significant correlation between IL-6 or TNF
mRNA levels and values of blood pressure or renal function under anaesthesia and
surgical stress. However, the inhibition of the IL-6 and TNF mRNAs in SHR was
prevented by propranolol treatment. These results suggested that suppression of
IL-6 and TNF mRNAs in the SHR kidney could be due to overactivity of beta
adrenergic influences which may importantly contribute to the development of
hypertension.
PMID- 9651108
TI - Influence of the antidepressants desipramine and fluoxetine on tryptophan-2,3
dioxygenase in the presence of exogenous melatonin.
AB - The effects of desipramine and fluoxetine were examined on rat hepatic tryptophan
2,3-dioxygenase activity in the presence or absence of exogenous melatonin. Male
Wistar rats were treated intraperitoneally over 8 days. The antidepressants were
also administered individually and their impact on the enzyme noted. Desipramine
reduced basal hepatic tryptophan-2,3-dioxygenase activity in the liver while
fluoxetine had no observable effect. However, fluoxetine also prevented the hemin
induced elevation in total enzyme activity. Exogenous melatonin (0.25mg/kg/day)
for 8 days counteracted the inhibitory effects of both desipramine and fluoxetine
at concentrations of 2.5mg/kg/day. Total enzyme activity was restored when
melatonin was administered in combination with either drug. The experimental
findings indicate that there is chemical antagonism at the surface of the enzyme
between melatonin and the antidepressants that abolishes the observed inhibitory
effects of the administered compounds.
PMID- 9651109
TI - Increased endogenous nitric oxide synthase inhibitor in patients with congestive
heart failure.
AB - Nitric oxide (NO) plays a role in controlling vascular tone and regulates the
contractile properties of cardiac myocytes. Patients with heart failure exhibit
high plasma levels of nitrite/nitrate (NOx), a stable metabolite of NO, and of
cytokines such as tumor necrosis factor-alpha, a potent inducer of NO synthase.
An increase in inducible NO synthase activity has been found in cardiac tissue
from patients with dilated cardiomyopathy. These findings raise the possibility
that local or systemic overproduction of NO induced by cytokines exerts a chronic
negative inotropic effect on the myocardium and may have detrimental effects on
systemic hemodynamics in patients with heart failure. Plasma levels of NG,NG
dimethylarginine (asymmetric dimethylarginine; ADMA), a circulating endogenous NO
synthase inhibitor, were measured in control subjects and patients with valvular,
hypertensive, or ischemic heart diseases or idiopathic cardiomyopathy. The plasma
levels of NOx and ADMA were assessed by high performance liquid chromatography.
The plasma levels of NOx and ADMA were significantly elevated in patients with
heart failure. Both NOx and ADMA were positively correlated with New York Heart
Association functional class. There was a significant inverse correlation between
plasma NOx and ejection fraction, as estimated by echocardiography. A significant
relationship between plasma NOx and ADMA was found only in patients with moderate
to severe heart failure (r=0.41, p=0.01). Findings suggest a compensatory role of
a circulating endogenous NO synthase inhibitor against induced NO synthase
activity in patients with heart failure.
PMID- 9651110
TI - Delta9-tetrahydrocannabinol, but not the endogenous cannabinoid receptor ligand
anandamide, produces conditioned place avoidance.
AB - Although exogenous cannabinoid ligands such as delta9-tetrahydrocannabinol (THC)
have been implicated in reward-related learning and aversion, the hedonic effects
of the endogenous cannabinoid agonist anandamide (arachidonylethanolamide) have
never been assessed. Thus, the effects of anandamide were tested in a place
conditioning task. Male Wistar rats received THC (0.0-8.0 mg/kg) or anandamide
(0.0-16.0 mg/kg) during conditioning sessions. The half-life of anandamide was
increased by pretreatment with the protease inhibitor phenylmethylsulfonyl
fluoride (2.0 mg/kg). A significant place aversion was found at the 1.0 and 1.5
mg/kg doses of THC. No significant place conditioning effects were found with
anandamide. Locomotor activity during conditioning was significantly decreased by
the 1.0, 1.5, 2.0 and 4.0 mg/kg doses of THC as well as the 8.0 and 16.0 mg/kg
doses of anandamide. These results fail to implicate the endogenous cannabinoid
anandamide in reward-related learning or aversion.
PMID- 9651111
TI - Cyclosporin A has low potency as a calcineurin inhibitor in cells expressing high
levels of P-glycoprotein.
AB - Cyclosporin A (CsA) is a widely-used immunosuppressant drug whose therapeutic and
toxic actions are mediated through inhibition of calcineurin (CN), a calcium- and
calmodulin-dependent phosphatase. Inhibition of CN by CsA requires drug binding
to its protein cofactor in the inhibition, cyclophilin. Because cyclophilin is a
high affinity target for CsA it is expected that this protein can act as a
reservoir for the drug in the cell and may be able to inhibit cellular efflux of
CsA. P-glycoprotein (P-gp) is known to increase the rate of CsA efflux from CsA
loaded cells but it is not clear if the P-gp drug efflux pump can compete
effectively with cyclophilin at therapeutically relevant concentrations of CsA.
To test the hypothesis that increased expression of P-gp confers protection
against CsA-dependent inhibition of CN phosphatase activity, KB-V cells
expressing varying levels of P-gp were analyzed to determine the potency of CsA
as a CN inhibitor. When intact cells were treated with CsA, a positive
correlation was observed between P-gp expression and resistance to CsA-dependent
inhibition of CN: the IC50 is approximately 20-fold higher in the multidrug
resistant epidermal carcinoma cell line, KB-V, which expresses P-gp at a high
level than in the parental, KB, cell line expressing very low levels of P-gp. The
resistance displayed by KB-V cells is abrogated by co-administration of the P-gp
inhibitor verapamil, whereas verapamil has no effect on CsA potency in control KB
cells. In cell lysates from KB-V cells with different amounts of P-gp CsA
exhibits equivalent potency, indicating that the difference in sensitivity to CsA
among the cell types requires maintenance of cell integrity. These observations
support the view that resistance to CN inhibition by CsA occurs in cells with
moderately elevated P-gp activity. Therefore, P-gp activity appears to be an
important determinant of CsA cellular specificity for both therapeutic and toxic
effects.
PMID- 9651112
TI - Measurement of acetylcholine released from rabbit detrusor smooth muscle using
HPLC with electro-chemical detection coupled with microdialysis procedure.
AB - We measured the amount of acetylcholine (ACh) released from rabbit detrusor
smooth muscles induced by electrical field stimulation (EFS) using microdialysis
procedure. The dialysis probe was inserted through the detrusor muscle strip and
was continuously perfused with a Ringer solution containing physostigmine
sulfate, at a rate of 2 microl/min. The strip was suspended in an organ bath
filled with the modified Krebs-Henseleit solution and then EFS was delivered. The
isometric force was recorded and monitored in each muscle preparation. The
dialysates were collected every 10 min. ACh was determined by a high performance
liquid chromatography with electro-chemical detection. The contraction of the
muscle strip and ACh release induced by EFS were increased in a frequency and
duration dependent manner. There were some differences between frequency response
curves of contraction and frequency dependent ACh release. In the contractile
response, the maximum contractions were observed at lower frequencies, while ACh
releases reached the maximum at higher frequencies. There was a significant, but
not simple correlation between EFS-induced contraction and ACh release. The
results suggest that this new method is useful to investigate the ACh release
from rabbit detrusor smooth muscles, and that other neurotransmitters than ACh
possibly contribute to EFS-induced contraction.
PMID- 9651113
TI - Pharmacological characterization of the pseudopterosins: novel anti-inflammatory
natural products isolated from the Caribbean soft coral, Pseudopterogorgia
elisabethae.
AB - Pseudopterosin E (PSE), a C-10 linked fucose glycoside and pseudopterosin A
(PSA), a C-9 xylose glycoside isolated from the marine gorgonian
Pseudopterogorgia elisabethae were both effective in reducing PMA-induced mouse
ear edema when administered topically (ED50 (microg/ear) PSE(38), PSA(8)) or
systemically (ED50 (mg/kg, i.p.) PSE (14), PSA (32)). Both compounds exhibited in
vivo analgesic activity in phenyl-p-benzoquinone-induced writhing (ED50 (mg/kg,
i.p.) PSE(14), PSA(4). PSE inhibited zymosan-induced writhing (ED50 = 6 mg/kg,
i.p.), with a concomitant dose-dependent inhibition of peritoneal exudate 6-keto
prostaglandin F1alpha (ED50 = 24 mg/kg) and leukotriene C4 (ED50 = 24 mg/kg). In
vitro, the pseudopterosins were inactive as inhibitors of phospholipase A2,
cyclooxygenase, cytokine release, or as regulators of adhesion molecule
expression. PSA inhibited prostaglandin E2 and leukotriene C4 production in
zymosan-stimulated murine peritoneal macrophages (IC50 = 4 microM and 1 microM,
respectively); however, PSE was much less effective. These data suggest that the
pseudopterosins may mediate their anti-inflammatory effects by inhibiting
eicosanoid release from inflammatory cells in a concentration and dose-dependent
manner.
PMID- 9651114
TI - Behaviour of human lymphocytic isoenzymes of 5'-nucleotidase.
AB - The behaviour of 5'-nucleotidase isoenzymes (ecto-5'-nucleotidase, e-Ns and c-N
II soluble 5'-nucleotidases) was studied in lymphocytes from patients with B-cell
chronic lymphocytic leukemia. A strong reduction in ecto- and soluble activities
was observed, although the pattern of the three 5'-nucleotidases did not always
strictly overlap. A significant decrease (p<0.05) in ecto-5'-nucleotidase, e-Ns
and c-N-II was found in B and T populations (B lymphocytes: 1.13, 0.88 and 1.26
nmol/h/10(6) cells versus 95.96, 9.64 and 13.73 nmol/h/10(6) cells in controls; T
lymphocytes: 1.31, 0.23 and 0.06 nmol/h/10(6) cells versus 9.25, 1.31 and 2.10
nmol/h/10(6) cells in healthy subjects). The percentage of ecto-5'-nucleotidase
positive cells (CD73+) was reduced in leukemia patients, indicating a lower
number of active molecules on the cell surface. The results of RT-PCR analysis
showed that the ecto-5'-nucleotidase mRNA of leukemia patients was not defective.
PMID- 9651115
TI - Parathyroid hormone-related protein increases DNA synthesis in proximal tubule
cells by cyclic AMP- and protein kinase C-dependent pathways.
AB - The present study was performed to characterize the possible involvement of cAMP
synthesis and protein kinase C (PKC) activation in the DNA synthesis-stimulating
effect of parathyroid hormone-related protein (PTHrP) in proximal tubule cells.
We found that DNA synthesis was stimulated by 10 microM 8BrcAMP, and 1 microM Sp
cDBIMPS, two cAMP analogs, and also by 1 microM phorbol 12-myristate 13-acetate
(PMA) and 100 microM 1,2-dioctanoyl-sn-glycerol, two PKC activators, and 10 nM
[Cys23] human (h)PTHrP (24-35) amide in rabbit proximal tubule cells (PTC). Both
Sp-cDBIMPS and PMA, at 1 microM, also increased DNA synthesis in SV40
immortalized mouse proximal tubule cells MCT. Human PTHrP (7-34) amide [PTHrP (7
34)] dose dependently stimulated DNA synthesis in a similar manner as
[34Tyr]PTHrP (1-34) amide [PTHrP (1-34)], in PTC. PMA pre-treatment for 20 h,
which downregulates PKC, completely blocked the effect induced by PTHrP (7-34),
but not that of PTHrP (1-34), in the latter cells. In contrast, the same PMA pre
treatment abolished the DNA synthesis stimulation by PTHrP (1-34) and PTHrP (7
34) in MCT cells, which appear to have PTH receptors mainly coupled to
phospholipase C and not adenylate cyclase. Our results indicate that the
stimulatory effect of PTHrP on DNA synthesis in proximal tubule cells is mediated
by a cAMP- and PKC-dependent mechanism.
PMID- 9651116
TI - Polyploidization and exit from cell cycle as mechanisms of cultured melanoma cell
resistance to methotrexate.
AB - Numerous malignant neoplasias are found to contain varying proportions of high
ploidy cells. Although the role they play in the tumor is poorly understood,
several lines of evidence suggest that these cells could be especially resistant
to various aggressions, a possibility of great interest in cancer treatment. In
the present study, we tested this hypothesis through the analysis of the presence
of high-ploidy cells following the administration of the chemotherapeutic agent
methotrexate. We also determined the expression of two proliferation markers,
PCNA and CDK1, after methotrexate-treatment. Cultured cells from the murine
melanoma B16F10 were treated with high doses of methotrexate for seven days prior
to determination of DNA content and proliferation markers. Our results showed an
obvious increase in the mean ploidy of this population. Specifically, there was a
dramatic reduction in the proportion of tetraploid cells (predominant in the
original population), and an increase in the proportion of cells with higher
ploidies, particularly those whose DNA content was greater than 8c, including
some cells with ploidies greater than 16c. Furthermore, there was a reduction in
the number of PCNA-expressing cells and the reduction was much more marked in the
case of CDK1 that was almost absent in the modal-ploidy treated cells. These
alterations concerning ploidy and expression of proliferation markers had
completely reverted two weeks after withdrawal of the drug. Our results indicate
that methotrexate at a high dosage selects a cell population heterogeneous
concerning its ploidy level, composed of one subpopulation of high-ploidy cells
and another of modal-ploidy cells that, considering its lack of CDK1 expression,
would remain in a latent state to evade the effects of the drug.
PMID- 9651117
TI - Inhibitory effects of berberine on voltage- and calcium-activated potassium
currents in human myeloma cells.
AB - The effects of berberine, an isoquinoline alkaloid, were investigated in human
myeloma cells. In cells with intracellular Ca2+ concentration ([Ca2+]i) = 10 nM,
the depolarizing square pulses from -80 mV elicited an instantaneous outward
current with an inactivation. This outward current was voltage dependent,
activating at -30 mV and showed inactivation with repetitive depolarization, and
was hence believed to be n type voltage-activated K+ current (IK(V)). Berberine
(30 microM) produced a prolongation in the recovery of IK(V) inactivation. In
cells with [Ca2+]i = 1 microM, berberine also inhibited A23187-induced IK(Ca).
Berberine (1-300 microM) caused the inhibition of IK(V) and IK(Ca) in the
concentration-dependent manners. The IC50 values of berberine-induced inhibition
of IK(V) and IK(Ca) were approximately 15 microM and 50 microM, respectively. In
inside-out configurations, berberine inside the pipette suppressed the activity
of K(Ca) channels without changing the single channel conductance. Berberine also
inhibited the proliferation of this cell line and the IC50 value of berberine
induced inhibition of cell proliferation was 5 microM. Thus, the cytotoxic effect
of berberine in cancer cells may be partially explained by its direct blockade of
these K+ channels.
PMID- 9651118
TI - Involvement of dopamine D1 and D2 receptors in Fos immunoreactivity induced by
stepholidine in both intact and denervated striatum of lesioned rats.
AB - Stepholidine (SPD), a natural product, has been demonstrated in previous studies
as a D1 agonist and D2 antagonist. In this work SPD-induced Fos immunoreactivity
was examined. In the normal rats, Fos was induced in the striatum by SPD (1-20
mg/kg, i.p.) dose-dependently. The distribution of Fos-positive cells induced by
SPD showed a rostral-caudal decline, matching the distribution of D2 dopamine
receptors. The Fos-positive cells were mainly found in striatal neurons
retrogradely labeled with horseradish peroxidase (HRP) from GP but not from SN,
and could be abolished by the pretreatment of a D2 agonist LY171555 (2 mg/kg,
i.p.), suggesting that the Fos expression in normal rats was due to the D2
antagonistic action of SPD. In the unilateral 6-hydroxydopamine-lesioned rats,
SPD (4 mg/kg, i.p.) induced Fos expression in intact and denervated side of the
striatum with different characteristics. Similar to that of normal rats, the Fos
expression in intact side possessed the rostral-caudal gradient and could be
abolished by the pretreatment of LY171555. However, in the denervated side, the
Fos positive cells were widely distributed, and mainly found in striatal neurons
retrogradely labeled from SN but not from GP. Furthermore, this expression was
prevented by the pretreatment of SCH23390 (0.2 mg/kg, i.p.) but not LY171555,
suggesting that the Fos expression in denervated side was due to the D1 agonistic
action of SPD. Therefore, we concluded that the Fos expression induced by SPD in
intact and denervated striatum was mediated via D2 and D1 receptor respectively,
supporting the previous standpoint that SPD possesses the dual action, i.e
antagonist to D2 and agonist to D1 receptors. Furthermore, it is suggested that
the contralateral turning behavior induced by SPD may result from the D1-mediated
excitation of striatonigral neurons of the denervated side of the lesioned rats.
PMID- 9651119
TI - Characterization of bradykinin receptors in human lung fibroblasts using the
binding of 3[H][Des-Arg10,Leu9]kallidin and [3H]NPC17731.
AB - Bradykinin (BK) receptors are involved in pain and inflammation. Two BK receptor
subtypes, B1 and B2, have been defined based on their pharmacological properties.
Both B1 and B2 receptors are G-protein coupled membrane receptors. B1 receptors
are present in smooth muscle tissue, whereas B2 receptors are found in both
smooth muscle tissue and neurons. [Des-Arg10,Leu9]kallidin (DALKD) is a selective
B1 receptor antagonist, and NPC17731 is a selective B2 receptor antagonist. To
develop binding assays for the two known BK receptor subtypes, [3H]DALKD and
[3H]NPC17731 were used as selective ligands for B1 and B2 receptors respectively.
Both ligands bound to the CCD-16 human lung fibroblast membranes reaching
equilibrium at 25 degrees C within 30 min. Binding was stable for at least 60
min. The Kd of [3H]DALKD was 0.33 nM and Bmax was 52 fmol/mg membrane protein.
The Kd of [3H]NPC17731 was 0.39 nM and Bmax was 700 fmol/mg membrane protein.
Competition for [3H]DALKD binding with BK receptor agonists was in the order:
[des-Arg10]KD (DAKD) > KD >> [des-Arg9]BK (DABK) > BK, and competition for
[3H]DALKD binding with BK receptor antagonists was in the order: DALKD > [des
Arg10]Hoe 140 (DAHoe 140) > [des-Arg9,Leu8]BK (DALBK) > NPC17731 > Hoe 140 >
DNMFBK, suggesting that [3H]DALKD bound selectively to B1 receptors. By contrast,
competition for [3H]NPC17731 binding by BK agonists was in the order: BK > KD >>
DAKD > DABK, and competition for [3H]NPC17731 binding by BK antagonists was in
the order: NPC17731 = Hoe 140 >> DNMFBK > DAHoe 140 > DALBK > DALKD, indicating
that [3H]NPC17731 labeled B2 receptors selectively. These results demonstrate
that [3H]DALKD and [3H]NPC17731 can be used with CCD-16 human lung fibroblast
membranes to provide a pair of binding assays for the simultaneous evaluation of
B1 and B2 BK receptor subtypes.
PMID- 9651120
TI - The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R)
in the rat hypothalamus and midbrain during restraint stress.
AB - Over the past few years, it has been reported that physical and psychological
stress elevate plasma interleukin-6 (IL-6), and that neural cells can produce IL
6 and have receptors for IL-6 (IL-6R). However, it is unknown whether IL-6 plays
a role in regulating the functions of neural cells in response to stress. We
demonstrated recently, using the reverse transcriptase-polymerase chain reaction
(RT-PCR), that the levels of mRNAs for IL-6 and IL-6R in the rat brain are
changed by restraint stress for four hours. In the present study, we investigated
the expression of mRNAs for IL-6 and the IL-6R in the rat hypothalamus and
midbrain during restraint stress. After rats had been restrained for 10, 30, 60,
120 or 240 min, the hypothalamus and midbrain were removed immediately and levels
of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. The
expression of mRNAs for IL-6 and IL-6R in both regions was reduced after short
term (30-60 min) restraint stress and tended to return toward the control level
after 120 min restraint stress. After long-term (240 min) restraint stress, the
level of IL-6 mRNA was significantly increased in the midbrain, while the level
of IL-6R mRNA was significantly reduced in both regions. These findings suggest
that the need for IL-6 might decline after short-term restraint stress and,
moreover, that the synthesis and secretion of IL-6 might be enhanced and IL-6
might be needed as a neurotrophic factor in the midbrain after long-term stress.
PMID- 9651121
TI - The relationship between circadian patterns of salivary cortisol and endogenous
inhibitor of monoamine oxidase A.
AB - The circadian pattern of free cortisol, measured in saliva, was monitored in
normal healthy adults (N=41) for the first half hour immediately after awakening
and in a smaller group (N=8) at timed intervals throughout the day. The
endogenous inhibitor of monoamine oxidase A (MAO-AI) was measured in the same
saliva samples in order to explore the relationship between circadian activation
of the hypothalamic-pituitary-adrenocortical (HPA) axis and MAO-AI. A marked
elevation of salivary cortisol was recorded in the first half hour immediately
after awakening resulting in a two to three fold increase from the first
awakening level. By contrast MAO-AI was highest immediately upon awakening and
fell subsequently. Hence the cortisol response to awakening is preceded by
heightened MAO-AI. Moreover those subjects who showed more persistently elevated
MAO-AI were characterised by a more pronounced cortisol response. An association
between MAO-AI and cortisol was also manifest in the diurnal pattern recorded at
timed intervals throughout the day. The decline of salivary cortisol from the
morning acrophase to the evening nadir was paralleled by MAO-AI. Both patterns of
decline were significant (P< 0.01). Taken together with previously reported
psychological stress studies these findings suggest a possible relationship
between MAO-AI and HPA activity.
PMID- 9651122
TI - Effect of chronic administration of Ginkgo biloba extract or Ginkgolide on the
hypothalamic-pituitary-adrenal axis in the rat.
AB - The hypersecretion of glucocorticoids during exposure to various stressors may
induce or worsen pathological states in predisposed subjects. Therefore it is of
interest to evaluate drugs able to reduce glucocorticoid secretion. It has
recently been shown that chronic administration of a Ginkgo biloba extract (EGb
761) inhibits stress-induced corticosterone hypersecretion through a reduction in
the number of adrenal peripheral benzodiazepine receptors. The present study was
designed to analyze the effect of EGb 761 and one of its components, Ginkgolide B
on the biosynthesis and secretion of CRH and AVP, the hypothalamic neurohormones
that regulate the pituitary-adrenal axis. Chronic administration of EGb 761 (50
or 100 mg/kg p.o. daily for 14 days) reduced basal corticosterone secretion and
the subsequent increase in CRH and AVP gene expression. Under the same
conditions, surgically-induced increase in CRH secretion was attenuated while the
activation of CRH gene expression, ACTH and corticosterone secretion following
insulin-induced hypoglycemia remained unchanged. Chronic i.p. injection of
Ginkgolide B reduced basal corticosterone secretion without alteration in the
subsequent CRH and AVP increase. However, the stimulation of CRH gene expression
by insulin-induced hypoglycemia was attenuated by Ginkgolide B. These data
confirm that the administration of EGb 761 and Ginkgolide B reduces
corticosterone secretion. In addition, these substances act also at the
hypothalamic level and are able to reduce CRH expression and secretion. However
the latter effect appears to be complex and may depend upon both the nature of
stress and substance (Ginkgolide B or other compounds of EGb 761).
PMID- 9651123
TI - The repetitive activation of extracellular signal-regulated kinase is required
for renal regeneration in rat.
AB - In this study, we investigated the activation of p42 extracellular signal
regulated kinase (ERK2) during renal regeneration after HgCl2-induced acute renal
failure (ARF) in rat. ERK2 activation was observed at 5 and 29 hr after HgCl2
injection, respectively. The tyrosine phosphorylation of hepatocyte growth factor
receptor (c-MET) occurred between 2.5 and 5 hr after the treatment. On the other
hand, the phosphorylation of epidermal growth factor receptor (EGFR) was
transiently observed at 29 hr after the injection. The peak of ornithine
decarboxylase activity as a marker of G1 phase was at 10 hr, and subsequently the
labeling index of proliferating cell nuclear antigen as a marker of S phase
increased at 53 hr. These results indicate that the repetitive activation of ERK2
related to the phosphorylation of c-MET and EGFR is required for the renal
regeneration in HgCl2-induced ARF of rat.
PMID- 9651124
TI - Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes.
AB - Curcumin is a natural phenolic compound found in the rhizomes of Curcuma longa
and endowed with beneficial biological activities including antioxidant,
anticarcinogenic and hepatoprotective effects. In this study curcumin was tested
for its potential ability to interact in vitro with hepatic P-glycoprotein (Pgp),
in a model system represented by primary cultures of rat hepatocytes, in which
spontaneous overexpression of multidrug resistance (mdr) genes occurs. In both
freshly-plated hepatocytes, containing low levels of Pgp, and 72 hour-cultured
hepatocytes, containing high levels of Pgp, the Rhodamine-123 (R-123) efflux,
which represents a specific functional test for Pgp-mediated transport, was
inhibited by curcumin in a dose-dependent manner. Western blot analysis showed
that 25microM curcumin, when included in the culture medium throughout the
experimental observation (72 hours), was able to significantly lower the increase
of mAb C219-immunoreactive protein spontaneously occurring in the cells during
culture. Curcumin, at doses ranging from 50 to 150microM was cytotoxic for
freshly-plated hepatocytes, as shown by the strong decrease in the cell ability
to exclude trypan blue 24 hours later, but it was significantly less cytotoxic
when added to 24 or 48 hour-cultured cells. The resistance to curcumin,
progressively acquired by cells during culture, was significantly reduced by high
concentrations of dexamethasone (DEX) or dimethyl-sulfoxide (DMSO), culture
conditions known to inhibit the spontaneous overexpression of Pgp. In addition,
in a concentration-dependent manner, verapamil reverted curcumin resistance in
Pgp overexpressing hepatocytes. In photoaffinity labeling studies, curcumin
competed with azidopine for binding to Pgp, suggesting a direct interaction with
glycoprotein. These results suggest that curcumin is able to modulate in vitro
both expression and function of hepatic Pgp and support the hypothesis that
curcumin, a chemopreventive phytochemical, could reveal itself also as a compound
endowed with chemosensitizing properties on mdr phenotype.
PMID- 9651125
TI - Lack of cisplatin-ranitidine kinetic interactions: in vivo study in children, and
in vitro study using dog renal brush border membrane vesicles.
AB - The interactions between cisplatin and organic ions have been extensively
investigated in animal models for the potential to reduce cisplatin cellular
uptake and resultant nephrotoxicity. To further investigate the beneficial
interaction clinically, we studied the effects of the organic cation, ranitidine,
on the renal handling of cisplatin in children. In parallel, we examined the
effects of cisplatin on the uptake kinetics of organic cations and anions by
brush border membrane vesicles (BBMV) prepared from dog renal cortex. The results
indicate that: 1) there is no measurable effect of ranitidine on renal clearance
of cisplatin in children; and 2) BBMV uptake of anionic p-aminohippurate, but not
cationic N-methylnicotinamide, is inhibited by cisplatin at concentrations of <1
mM. These findings suggest that cisplatin may not share transport systems with
organic cations to a clinically significant degree. Assuming that renal tubular
transport is a prerequisite for cisplatin nephrotoxicity, the lack of apparent
kinetic interactions between cisplatin and organic cations may preclude clinical
use of organic cations as a modality to prevent cisplatin nephrotoxicity.
PMID- 9651126
TI - Feature article: are neurons lost from the primate cerebral cortex during normal
aging?
PMID- 9651127
TI - Impaired performance in a conditioned reaction time task after thermocoagulatory
lesions of the fronto-parietal cortex in rats.
AB - The present study examined whether cortical damage in rats may disrupt the
integrative processes and motor control involved in the performance of a reaction
time (RT) task. To investigate the nature of the deficits in the conditioned
task, rats were subjected, after learning, to a coagulation of pia brain surface
of varying extent, including the frontal and parietal cortical areas. They were
then tested daily for over one month. The behavioural task required the rats to
hold a lever down during a variable and random delay and react quickly to the
onset of a visual cue by releasing the lever within a RT limit for food
reinforcement. Extensive bilateral cortical lesions had no effect on spontaneous
motor activity, but severely impaired RT performance. Latencies to release the
lever after the cue were dramatically increased during the first postoperative
sessions and gradually returned to baseline levels within 3 weeks, whereas less
dramatic but long-lasting increase in premature responding (anticipatory response
before the visual cue) was observed throughout the testing sessions. More
restricted lesions to the frontoparietal cortex produced a similar pattern of
incorrect responding with a faster recovery of delayed responses and a strong
deficit in premature responding. The major effects of lesions confined to the
rostral pole of the frontal cortex were observed on premature responding,
however. The present results demonstrate that the impairment in movement
initiation is rapidly recovered within 2-3 weeks even after extensive
thermocoagulatory lesions of the frontal and parietal areas. This recovery
suggests the involvement of adaptive processes developing progressively and
probably reflecting the remarkable synaptic plasticity of the extrapyramidal
motor output. In contrast, the long-lasting increase in premature responding,
supposed to reflect some attentional deficits, may produce anatomofunctional long
term disorganization of subcortical structures such as the basal ganglia.
Interestingly enough, these results show that the rat neocortex supports
functions very similar to those of primates and provide a good model for studying
these higher functions in operant motor procedures that require prior associative
learning and appropriate motor coordination.
PMID- 9651128
TI - Integrating electrophysiological and anatomical experimental data to create a
large-scale model that simulates a delayed match-to-sample human brain imaging
study.
AB - We propose a model that draws together experimental evidence from anatomical,
electrophysiological and imaging experiments in order to understand better the
neural substrate of human imaging studies using positron electron tomography
(PET) and functional magnetic resonance imaging (fMRI). First, we define a simple
local circuit that reflects the major role that local connectivity plays in
producing PET and fMRI data, which are thought to mainly reflect synaptic
activity. Second, in order to account for the role of varying behaviors during
the course of a typical imaging experiment, we propose a local circuit that can
perform a delayed match-to-sample task. The elements of this circuit behave very
much like neurons that have been found in the prefrontal cortex during similar
tasks in monkeys. One subpopulation responds selectively only when stimuli are
present. Two different populations show the two types of delay-period activity
that have been identified, one with high activity both during the cue and the
delay period, the other with a rise during the delay period only. Last, a
subpopulation shows a brief response only if the second stimulus matches the
first, thus mediating the decision about whether the stimuli match. We show that
in addition to performing the task, the integrated summed synaptic activities of
the model are similar to experimental PET data.
PMID- 9651129
TI - Widespread origin of the primate mesofrontal dopamine system.
AB - The dopaminergic innervation of the frontal cortex, commonly implicated in
psychiatric and neurological disorders, has traditionally been associated with a
circumscribed midline group of ventral tegmental area (VTA) neurons. We have
employed a combination of retrograde tracing, using fluorescent dyes, and
tyrosine hydroxylase (TH) immunohistochemistry to amplify knowledge of frontal
cortex-projecting dopamine (DA) neurons in non-human primates. Injections of
retrograde fluorochromes were made in areas 46, 8B/6M, 12, 4, 24, and the
prelimbic (PL) and infralimbic areas (IL) of the rhesus monkey. The mesencephalic
distribution of neurons exhibiting both retrograde labeling and TH
immunoreactivity or retrograde labeling alone was examined from the level of the
mammillary bodies to the locus coeruleus. DA afferents innervating the macaque
frontal cortex as a whole originate from an unexpectedly widespread continuum of
neurons distributed in the dorsal aspects of all three of the mesencephalic DA
cell groups [A9, A10 and A8; generally corresponding to the DA cells of the
substantia nigra (SN), VTA, and the retrorubral area (RRA) respectively]. A large
number of these retrogradely labeled neurons are non-dopaminergic. The dorsal
frontal cortex (areas 46, BB/6M and 4) receive DA projections primarily from the
full medial-lateral extent of A9 cells dorsal to the SN pars compacta (i.e. A9
dorsalis), the RRA and to a lesser extent from the A10 parabrachial pigmented
nucleus (PBPG) and linear nuclei, the latter of which have been associated with
the mesocortical DA system. In contrast, the ventromedial PL and IL exhibit a
significantly more robust input from the PBPG and midline linear VTA nuclei than
from the lateral groups. The anterior cingulate cortex (area 24) is innervated by
a group of DA neurons primarily located between these laterally and medially
concentrated populations. These findings demonstrate a degree of
compartmentalization of the mesofrontal DA system in primates, and suggest that
this projection should no longer be viewed as a unitary midline system.
PMID- 9651130
TI - Behavioral constraints in the development of neuronal properties: a cortical
model embedded in a real-world device.
AB - The ability of organisms to categorize diverse and often novel stimuli depends on
ongoing interactions with their environment. In a modality such as vision,
categorization requires the generation of both selective and invariant responses
of cortical neurons to complex visual stimuli. How does behavior contribute to
shaping the responses of these neurons? Analysis of this question is made
difficult by the complex multilevel interactions between many neural and
behavioral variables. To mitigate this difficulty, we studied the development and
ongoing plasticity of pattern-selective neuronal responses by means of synthetic
neural modeling. For this purpose, we constructed Darwin V, which consists of a
simulated neuronal model embedded in a real-world device that is capable of
motion and autonomous behavior. The neuronal model consists of four major
components: a visual system (containing cortical and subcortical networks); a
taste system based on conductance; sets of motor neurons capable of triggering
behavior; and a diffuse ascending (value) system. The modeled visual cortex
consists of two areas: a topographic map responsive to elementary features
connected to a higher-order map composed of initially non-selective neuronal
units. During behavior over time in its environment, Darwin V encounters numerous
objects consisting of black metal cubes displaying different patterns of white
blobs and stripes. Initially, the lack of specific higher-order visual responses
does not allow visual pattern discrimination, and appetitive and aversive
behaviors are triggered by the 'taste' (surface conductivity of objects) alone.
In the course of sensory experience, however, changes occur in visual and
sensorimotor connection strengths, with two major consequences. First, units
within the higher visual area acquire responses that are both pattern selective
and translation invariant. Second, as a result of the operation of the value
system, these responses become linked to appropriate behaviors. Analysis of
Darwin V after such changes indicates that the continuity of self-generated
movements is essential for the development of pattern-selective and translation
invariant responses. The concomitant development of a preference for foveal over
parafoveal objects was found to be due to increased behavioral interactions with
object cubes gripped by the centrally mounted effector (snout) of Darwin V.
Finally, even after development of higher-order visual responses, visual
responses to more frequently encountered objects continued to be enhanced, while
other responses were diminished. Overall, the detailed study of Darwin V over
multiple levels of organization provides a heuristically revealing example of the
crucial role played by behavioral and environmental interactions in the
development of complex responses by specialized neurons.
PMID- 9651131
TI - Direction selectivity in the middle lateral and lateral (ML and L) visual areas
in the California ground squirrel.
AB - Extracellular recordings obtained from the extrastriate cortex of the California
ground squirrel, a diurnal sciurid, show that large receptive fields and a strong
direction selectivity are present in the middle lateral area (ML) and the lateral
area (L), located laterally to V2 and V3. Direction selectivity was tested by
presenting stimuli of varying dimensions, shapes and speeds at different
locations in the visual field. Most cells in ML and L (84%) were direction
selective, with a preference for fast speeds, indicating that these areas share a
role in motion processing. Areas ML and L may be homologous to area MT or may
represent a case of homoplasia. A directional anisotropy for motion towards the
vertical meridian was found in ML and L cells, suggesting that these areas may be
involved in detecting predators and other moving objects coming from the
periphery, rather than in processing flow fields caused by forward locomotion,
for which a centrifugal bias might be expected.
PMID- 9651132
TI - Gyri of the human neocortex: an MRI-based analysis of volume and variance.
AB - This magnetic resonance imaging (MRI)-based morphometric analysis of cortical
topography in the human brain is based upon the segmentation and parcellation of
volumetric T1-weighted MRI data for a set of 20 young adult brains including 10
males and 10 females. For the most part, each parcellation unit (PU) of the
neocortex corresponds to a single or a portion of a single gyrus. The volumes of
each PU were computed for each brain. Subsets of PUs were also grouped so as to
represent the neocortex for the frontal, temporal, parietal and occipital lobes.
The coefficient of variation of the mean volume of total neocortex and that of
the neocortex assigned to individual lobes cluster around 10%, whereas that of
neocortex assigned to the individual gyri (PU) is more than twice that value.
Approximately 80% of the total variance in gyral volume arises from determinants
interactive for individual and specific gyri, while only approximately 10% of the
total variance appears to be a reflection of uniform scaling to total neocortical
volume. Sexual dimorphism contributes a pervasive though relatively small
component of this variance. These results have implications for the study of
structure-function correlation, and the proper statistical methods of handling
volumetric data in morphometric studies. In addition, the nature of the
covariance structure of the data will lead to future hypotheses regarding the
relationships between the various potential genetic and epigenetic gyral
influencing factors.
PMID- 9651133
TI - Psychological morbidity in caregivers is associated with depression in patients
with dementia.
AB - The relationship between psychological morbidity in caregivers and depression in
patients with dementia was examined using data collected on 193 patient-caregiver
dyads attending a memory disorders clinic. Caregivers had high rates and levels
of psychological morbidity which were associated with the severity of dementia
(but neither the type nor duration), with the caregiver being a spouse and female
and living with the person with dementia. A logistic regression analysis
identified clinician-rated patient depression score and demanding problem
behaviors as being independently and significantly associated with caregiver
psychological morbidity. This new finding of a link between patient depression
and caregiver psychological morbidity has implications for more focused treatment
programs for both caregivers and patients.
PMID- 9651134
TI - Carnitine acyltransferases are not changed in Alzheimer disease.
AB - We evaluated the activities of carnitine palmitoyltransferase (CPT), carnitine
octanoyltransferase (COT), and carnitine acetyltransferase (CAT) in the frontal
cortex, temporal cortex, parietal cortex, hippocampus, and cerebellum of
Alzheimer disease (AD) patients and normal human brains. There were no
significant differences in total CPT activity, its inhibition by malonyl-CoA, the
effect of the detergent Triton X-100 on CPT activity, COT activity, and CAT
activity in any of the brain regions examined whether activities were expressed
as grams of wet weight or corrected for noncollagen protein content. The addition
of Triton X-100 increased CAT activity by 50%. Our results suggest that there is
no defect of fatty acid transport within the AD brain cell. Total CPT activity,
COT activity, and CAT activity are not affected in AD nor is the ratio of CPT I
to CPT II altered in the AD versus the normal human brain.
PMID- 9651135
TI - Limited effect of neuritic plaques on neuronal density in the hippocampal CA1
area of Alzheimer patients.
AB - Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are the classic
neuropathological hallmarks of Alzheimer disease (AD). It is generally assumed
that the pathogenic process of AD could start by local neurotoxicity induced by
the beta-amyloid core of plaques, followed by the appearance of NFTs and
eventually cell death. To determine whether or not local neurotoxicity around NPs
is indeed a major pathogenetic mechanism, we used an image analysis system to
measure the neuronal density around Bodian-stained NPs in the hippocampal CA1
area of eight AD patients. Neuronal density, as measured within two arbitrary
concentric circles around NPs with a radius of 74 and 123.5 microm, respectively,
was on average 19% and 16% lower than the density in similar control circles
without NPs in the same section. Furthermore, neuronal density around NPs was
inversely related to their size. To investigate the impact of such a local
reduction in cell density around NPs on the entire CA1 area, we also determined
the proportion of the CA1 covered by the NPs and the arbitrary concentric circles
around them. This appeared to be 16.3% of the total CA1 area, which means that
the negative effect of NPs on the cell density can only explain 2.6% of cell
death in the entire CA area. In conclusion, this study suggests that although NPs
have a local negative effect on neighboring neurons, their contribution to the
strong decrease in CA1 cell numbers is limited.
PMID- 9651136
TI - Silicon reduces aluminum accumulation in rats: relevance to the aluminum
hypothesis of Alzheimer disease.
AB - In recent years, a possible relation between the aluminum and silicon levels in
drinking water and the risk of Alzheimer disease (AD) has been established. It
has been suggested that silicon may have a protective effect in limiting oral
aluminum absorption. The present study was undertaken to examine the influence of
supplementing silicon in the diet to prevent tissue aluminum retention in rats
exposed to oral aluminum. Three groups of adult male rats were given by gavage
450 mg/kg/day of aluminum nitrate nonahydrate 5 days a week for 5 weeks.
Concurrently, animals received silicon in the drinking water at 0 (positive
control), 59, and 118 mg Si/L. A fourth group (-Al, - Si) was designated as a
negative control group. At the end of the period of aluminum and silicon
administration, urines were collected for 4 consecutive days, and the urinary
aluminum levels were determined. The aluminum concentrations in the brain
(various regions), liver, bone, spleen, and kidney were also measured. For all
tissues, aluminum levels were significantly lower in the groups exposed to 59 and
118 mg Si/L than in the positive control group; significant reductions in the
urinary aluminum levels of the same groups were also found. The current results
corroborate that silicon effectively prevents gastrointestinal aluminum
absorption, which may be of concern in protecting against the neurotoxic effects
of aluminum.
PMID- 9651137
TI - Guidelines for conducting bridging studies in Alzheimer disease.
AB - This report provides guidelines for conducting bridging studies in patients with
Alzheimer disease (AD). Bridging studies are late phase I safety/tolerance
studies that determine the maximum tolerated dose (MTD) in patients before phase
II efficacy studies are initiated, facilitating the transition from phase I to
phase II development. Determining the MTD in patients maximizes the potential to
detect efficacy by permitting the use of the highest tolerated doses in phase II
while providing a good understanding of potential adverse events. Bridging
studies should be double-blind, placebo-controlled, inpatient studies conducted
in acute-care facilities by clinical personnel who are equipped to handle
unexpected contingencies under the oversight of a competent, multidisciplinary
review board. Patients should be in good physical health (excluding AD), and a
comprehensive informed consent procedure must be instituted. We recommend
initially using a fixed-dose panel design with a dose schedule based on the MTD
in normal volunteers and later establishing the dose titration MTD.
PMID- 9651138
TI - Safety of tacrine: clinical trials, treatment IND, and postmarketing experience.
AB - The safety of tacrine (Cognex), a centrally active, reversible
acetylcholinesterase inhibitor approved in 1993 for the treatment of mild to
moderate dementia of the Alzheimer type, was evaluated in 2,706 patients with
Alzheimer disease (AD) in clinical trials and in 9861 patients with AD in a
treatment investigational new drug (TIND) program. More than 190,000 patients in
the United States received tacrine during the first 2 years following marketing
approval. The most common tacrine-associated adverse events were elevated liver
transaminase levels [alanine aminotransferase (ALT) and, to a lesser degree,
aspartate aminotransferase] and peripheral cholinergic events involving primarily
the digestive system (nausea, vomiting, diarrhea, dyspepsia, anorexia, and weight
loss). Based on clinical trial experience, potentially clinically significant (>3
x upper limit of normal) ALT elevations occurred in 25% of patients, requiring
routine monitoring early in treatment. The elevations were almost always
asymptomatic, rarely accompanied by significant increases in bilirubin, and
related to time on drug rather than to dose (90% occurred within the first 12
weeks of treatment). Gastrointestinal events were related to dose and generally
of mild to moderate intensity. Tacrine-associated events, including ALT
elevations, were reversible. Cholinergic events were manageable with dosage
adjustment. Tacrine was not associated with permanent liver injury in clinical
trials or a TIND setting.
PMID- 9651139
TI - Activation of the contact system in cerebrospinal fluid of patients with
Alzheimer disease.
AB - Several converging lines of evidence suggest that beta-amyloid and inflammation
may be linked in the pathogenesis of Alzheimer disease (AD), but the mechanism of
beta-amyloid neurotoxicity is unclear. In this study, by demonstrating that high
molecular weight kininogen may be massively cleaved in the cerebrospinal fluid
(CSF) of patients with AD, we provide evidence of the potential involvement of
the contact system in the inflammatory processes taking place in this disease. In
the CSF of patients with neuroimmune inflammatory disease (multiple sclerosis,
chronic inflammatory demyelinating polyneuropathy), there was no evidence of
increased cleavage of high molecular weight kininogen, suggesting that this
finding may be characteristic of the Alzheimer brain. The data obtained from in
vitro experiments seem to indicate that the cleavage of high molecular weight
kininogen in vivo may be the result of the interaction of beta-amyloid with
factor XII and of kallikrein generation. The actual relevance of such a
phenomenon remains to be established in vivo. However, the demonstration that the
contact system may be activated in the brains of Alzheimer patients points to the
potential involvement of the kallikrein-kinin system in the inflammatory process
of this disease.
PMID- 9651140
TI - Bromocriptine treatment for perseveration in demented patients.
AB - Some forms of behavioral perseveration may reflect the disruption of specific
neurotransmitter systems including mesencephalic dopaminergic projection. We
present an open-labeled trial of a dopamine agonist for treating perseveration in
dementia. Eight patients with ischemic vascular or degenerative dementia
completed a 25-day trial of bromocriptine with a maximum daily dose of 10 mg.
Patients were assessed with neuropsychological scales and a test battery for
detecting perseveration. Recurrent and stuck-in-set types of perseveration
significantly improved during the treatment, whereas measures for general
attention and overall cognitive function showed no significant changes. We assume
that bromocriptine supplemented the mesolimbocortical or ventral mesostriatal
dopamine system ameliorated a certain frontal lobe function such as focused
attention or working memory and improved the patients' perseverations. Although
this study is preliminary because of the small sample size and open-labeled
design, the results underline the possibility of pharmacotherapy for
perseveration and recommend a double-blind, placebo-controlled study.
PMID- 9651141
TI - Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm
disturbances in Alzheimer disease.
AB - In patients with Alzheimer disease (AD), an irregular day-night rhythm with
behavioral restlessness during the night makes a strong demand on caregivers and
is among the most important reasons for institutionalization. A dysfunctioning
circadian timing system is supposed to underlie the disturbance or at least to
contribute to it. The disturbance improves with increased environmental light,
which, through the retinohypothalamic tract, activates the suprachiasmatic
nucleus (SCN), the biological clock of the brain. Because recent studies have
indicated both direct and indirect spinal projections to the SCN, we investigated
whether excitation of spinal neurons by means of transcutaneous electrical nerve
stimulation (TENS) could also improve circadian rhythm disturbances in AD
patients. The actigraphically obtained rest-activity rhythm of 14 AD patients
showed an improvement in its coupling to Zeitgeber after TENS treatment but not
after placebo treatment.
PMID- 9651142
TI - Three novel missense mutations in unrelated Japanese patients with type I and
type II protein S deficiency and venous thrombosis.
AB - A molecular analysis of protein S deficiency in three unrelated Japanese patients
was performed. An approximately 50% reduction in both functional and immunologic
levels of protein S was detected in the plasmas from two unrelated patients,
designated protein S Osaka 1 and protein S Osaka 2. An approximately 50%
reduction in the functional level, but a normal immunologic level of protein S,
was detected in plasma from a third patient, designated protein S Osaka 3. All of
the exons and exon/intron junctions of the protein S gene were studied using a
strategy combining polymerase chain reaction amplification and rapid non
radioactive single-strand conformational polymorphism analysis. We identified a G
to-A change in exon X of the protein S gene in protein S Osaka 1. This mutation
resulted in the substitution of Gly for Ser at position 295 in the sex hormone
binding globulin-like region. In protein S Osaka 2, a G-to-C change at the
position of the 3' end of exon III was identified, leading to the amino acid
substitution of Val46 by Leu in the aromatic stack region. In protein S Osaka 3,
an A-to-G change in exon II was identified, leading to the substitution of Lys9
by Glu in the Gla domain. It was concluded that the Gly295-to-Ser mutation and
Val46-to-Leu mutation cause type I protein S deficiency and that the Lys9-to-Glu
mutation causes type II deficiency.
PMID- 9651143
TI - Prevention of the influence of fibrin and alpha2-macroglobulin in the continuous
measurement of the thrombin potential: implications for an endpoint determination
of the optical density.
AB - We proposed the endogenous thrombin potential (ETP) as an overall function test
of the coagulation system. We recently introduced a routine test which requires
defibrinated plasma. In order to develop an assay in which the ETP-value can be
directly obtained by measuring the optical density, we investigated two methods
to inhibit fibrinogen clottability and to inactivate alpha2-macroglobulin. The
first method makes use of hydroxylamine to inactivate alpha2-macroglobulin and H
Gly-Pro-Arg-Pro-OH to inhibit fibrin polymerization. At pH 7.35, plasma incubated
with 25 mM hydroxylamine and 1.5 mg/mL H-Gly-Pro-Arg-Pro-OH for 5 minutes at 37
degrees C resulted in a reduced endlevel of the amidolytic activity on small
chromogenic substrates. The second method uses a metalloprotease purified from
Crotalus basiliscus to remove alpha2-macroglobulin from plasma in combination
with H-Gly-Pro-Arg-Pro-OH. Herein plasma is incubated with 3.5 LM protease during
15 minutes at 37 degrees C in the presence of 1 mg/mL polymerization inhibitor.
The enzymatic method results in a zero endlevel of the amidolytic activity and
this would imply that measurement of the ETP is reduced to an endpoint
determination of the optical density. We show that the endpoint determination of
the optical density correlates well with the calculated ETP in plasmas with
different degrees of anticoagulation.
PMID- 9651144
TI - Enhancement of thrombolysis in vivo without skin and soft tissue damage by
transcutaneous ultrasound.
AB - Previous studies have shown that transcutaneous ultrasound enhances thrombolysis
by streptokinase in animals in vivo; however, skin and soft tissue damage induced
by ultrasound energy has been a major limitation. The objective of this study was
to examine the efficacy of thrombolysis and damage to skin and soft tissues using
a newly designed concentrated ultrasound system with a cooling manifold. Using a
rabbit model with iliofemoral arterial thrombotic occlusions, 15 pairs of
arteries were randomized to receive ultrasound treatment or no ultrasound
treatment. Streptokinase (25,000 unit/kg) was given intravenously. Skin
temperature was maintained at 25-33 degrees C when ultrasound energy was applied.
The serum level of creatine kinase, lactate dehydrogenase, red blood cell counts,
and platelet counts were checked at baseline, after thrombus induction, and after
ultrasound treatment. Fifteen of fifteen (100%) iliofemoral arteries were
angiographically recanalized after ultrasound treatment. In contrast, only 1/15
(6.7%) contralateral arteries were patent after 1 hour. After the subsequent hour
with heparin the patency was 14/15 in the ultrasound treated group and 3/15 in
the control group. Histologically, the patent arteries had only minimal focal
mural thrombus, whereas the angiographically occluded arteries had occlusive
thrombi. There was no histologic evidence of ultrasound induced damage to
overlying skin, soft tissues, or arteries. In addition, there was no significant
rise of creatine kinase, lactate dehydrogenase, or decrease in red blood cell
counts and platelet counts induced by ultrasound. In conclusion, transcutaneous
concentrated ultrasound which significantly enhances streptokinase induced
thrombolysis in vivo can be delivered without concomitant tissue damage. This
simple combination therapy has clinical potential for safely treating patients
with arterial or venous thromboses.
PMID- 9651146
TI - Species specificity of the anticoagulant activity of human urinary soluble
thrombomodulin.
AB - The anticoagulant activities of human urinary soluble thrombomodulin (UTM) in
blood taken from various species using several anticoagulant assay systems were
compared; it was examined which coagulant assay system is appropriate for
evaluation of the antithrombotic effects of UTM and how the species specificity
of UTM is involved in the mechanisms of action of UTM. When anticoagulant
activities were compared using activated partial thromboplastin time (APTT),
thromboelastography (TEG), and thrombin generation test (TGT), the effect of UTM
was found to be the strongest in humans among various species tested. Among the
anticoagulant assays tested, TGT reflecting protein C (PC) activation by UTM,
appeared to be more sensitive than APTT and TEG in detection of thrombomodulin
activity. In the study of the mechanisms of action of UTM, UTM exhibited nearly
the same antithrombin activity against human and rat thrombin; the rate of
activation of human PC by thrombin/UTM complex was much higher than that of rat
PC. Therefore, the species specificity of the anticoagulant activity of UTM may
be attributable to thrombin/UTM-PC interaction, but not to UTM-thrombin
interaction. From these results, we concluded that TGT reflecting PC activation
by UTM will be a more useful assay than APTT and TEG for estimating the
antithrombotic effects of UTM in humans. Furthermore, our findings suggest that
UTM will exhibit more potent antithrombotic effects in humans than those in rats
by strongly enhancing thrombin-catalyzed PC activation.
PMID- 9651145
TI - A kinetic analysis of the interaction of human recombinant tissue factor pathway
inhibitor with factor Xa utilizing and immunoassay and the effect of antithrombin
III/heparin on the complex formation.
AB - We have recently shown that a complex formation of tissue factor pathway
inhibitor (TFPI) and factor Xa (Xa) promotes a clearance of proteoglycans
associated TFPI. In the current studies, the interaction between human
recombinant TFPI (h-rTFPI) and Xa were kinetically analyzed by utilizing both a
protease inhibitor, p-(amidophenyl) methanesulfonyl fluoride hydrochloride, and a
specific enzyme-linked immunosorbent assay for the complex of h-rTFPI with Xa. We
further investigated the effect of antithrombin III on the complex formation
between h-rTFPI and Xa. We found that the h-rTFPI/Xa complex formed in a time
dependent manner: the second-order rate constant (K1) for the complex formation
was calculated to be 0.86x10(6) M(-1)s(-1). The addition of antithrombin III to
the h-rTFPI solution modestly reduced the rate of the complex formation between h
rTFPI and Xa. Heparin strikingly enhanced antithrombin III's inhibition of Xa and
resulted in complete abrogation of the complex formation between h-rTFPI and Xa
in the absence or presence of acidic phospholipids. Furthermore, antithrombin III
induced dissociation of the preformed h-rTFPI/Xa complex in the presence of
heparin. These results suggest that in the presence of heparin, antithrombin III
interferes with the catabolism of TFPI mediated via Xa.
PMID- 9651147
TI - Cost-effectiveness of venous thrombosis prophylaxis following ischemic stroke: an
assessment of currently available literature.
PMID- 9651148
TI - 1-[2(R)-(2-amino-2-methylpropionylamino)-3-(1H-indol-3-yl)propionyl]- 3
benzylpiperidine-3(S)-carboxylic acid ethyl ester (L-163,540): a potent, orally
bioavailable, and short-duration growth hormone secretagogue.
PMID- 9651149
TI - 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)
3-chlorophenyl]benzamide (VPA-985): an orally active arginine vasopressin
antagonist with selectivity for V2 receptors.
PMID- 9651150
TI - Substituted halogenated arylsulfonamides: a new class of sigma receptor binding
tumor imaging agents.
AB - The discovery of a series of novel halogenated arylsulfonamides (HAS) as new
sigma receptor binding tumor imaging agents is described. Several substituted
halogenated sulfonamides have been prepared and characterized. Target compounds
were examined for their affinity for sigma1 and sigma2 receptor subtypes using
guinea pig brain membranes and rat liver membranes, respectively. A number of
substituted halogenated sulfonamides displayed subnanomolar affinities for sigma1
sites and low nanomolar affinities for sigma2 subtype receptors. A limited
structure-activity relationship study of this chemical series is discussed. The
radioiodination (I-125) of one congener member (4-[125I]iodo-N-[2-(1'
piperidinyl)ethyl]benzenesulfonamide, 4-[125I]IPBS) was accomplished in high
yields. The in vitro competition binding studies of 4-[125I]IPBS in guinea pig
brain membranes with sigma receptor binding ligands confirmed its sigma
pharmacology. The rank order of potency was BD1008 (N-[2-(3, 4
dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) > 4-IPBS >
haloperidol > (+)-pentazocine > DTG (1, 3-di-o-tolylguanidine) > (-)-pentazocine.
The inhibition constants (IC50) were 0.70, 1.46, 6.28, 10.4, 87.2, and 152 nM,
respectively, and are consistent with labeling of sigma1 receptors. The tumor
imaging potential of 4-[125I]IPBS was studied in C57 black mice bearing B16
melanoma xenograft. A high tumor uptake of 4-[125I]IPBS was observed (7.40% ID/g)
at 1 h postinjection. The wash out of activity from the tumor was slow at 6 h
postinjection (7.22% ID/g). The tumor also had the highest amount of
radioactivity (1.54% ID/g) at 24 h postinjection. These results demonstrate that
radiohalogenated benzenesulfonamides could be a potentially useful class of
compounds in nuclear oncologic scintigraphy.
PMID- 9651151
TI - Structure-activity relationship studies of novel carbocyclic influenza
neuraminidase inhibitors.
AB - A series of influenza neuraminidase inhibitors with the cyclohexene scaffold
containing lipophilic side chains have been synthesized and evaluated for
influenza A and B neuraminidase inhibitory activity. The size and geometry of
side chains have been modified systematically in order to investigate structure
activity relationships of this class of compounds. The X-ray crystal structures
of several analogues complexed with neuraminidase revealed that the lipophilic
side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224,
and Ile222 of the enzyme active site. The structure-activity relationship studies
of this series have also demonstrated remarkably different inhibitory potency
between influenza A and B neuraminidase. This indicated that the lipophilic side
chains had quite different hydrophobic interactions with influenza A and B
neuraminidase despite their complete homology in the active site. Influenza B
neuraminidase appeared to be much more sensitive toward the increased steric
bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive
structure-activity relationship investigation reported in this article, GS 4071
emerged as one of the most potent influenza neuraminidase inhibitors against both
influenza A and B strains.
PMID- 9651152
TI - Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray
crystallographic analysis, and structure-activity relationships for a series of
P2-modified, orally active peptidyl pentafluoroethyl ketones.
AB - A series of P2-modified, orally active peptidic inhibitors of human neutrophil
elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were
designed using pentafluoroethyl ketone 1 as a model. Rational structural
modifications were made at the P3, P2, and activating group (AG) portions of 1
based on structure-activity relationships (SAR) developed from in vitro (measured
Ki) data and information provided by modeling studies that docked inhibitor 1
into the active site of HNE. The modeling-based design was corroborated with X
ray crystallographic analysis of the complex between 1 and porcine pancreatic
elastase (PPE) and subsequently the complex between 1 and HNE.
PMID- 9651153
TI - New chemical descriptors relevant for the design of biologically active peptides.
A multivariate characterization of 87 amino acids.
AB - In this study 87 amino acids (AA.s) have been characterized by 26 physicochemical
descriptor variables. These descriptor variables include experimentally
determined retention values in seven thin-layer chromatography (TLC) systems,
three nuclear magnetic resonance (NMR) shift variables, and 16 calculated
variables, namely six semiempirical molecular orbital indices, total, polar, and
nonpolar surface area, van der Waals volume of the side chain, log P, molecular
weight, and four indicator variables describing hydrogen bond donor and acceptor
properties, and side chain charge. In the present study, the data from a previous
characterization of 55 AA.s from our laboratory have been extended with data for
32 additional AA.s and 14 new descriptor variables. The new 32 AA.s were selected
to represent both intermediate and more extreme physicochemical properties,
compared to the 20 coded AA.s. The new extended and updated principal property
scales, the z-scales, were calculated and aligned to previously reported z(old)
scales. The appropriateness of the extended z-scales were validated by the use in
quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues
and in a QSAM of 29 neurotensin analogues.
PMID- 9651154
TI - Design of a new class of orally active fibrinogen receptor antagonists.
AB - The integrin receptor recognition sequence Arg-Gly-Asp was successfully used as a
template from which to develop a series of potent, selective, orally active,
peptide-based fibrinogen receptor antagonists with a long duration of action.
Simple modifications centered on the Arg and Gly residues quickly led to a
modified peptide (1) with significantly enhanced ability to inhibit in vitro
platelet aggregation. Substitution of the guanidino group in 1 by piperidine
provided 3, which showed not only a further increase in potency but also a modest
degree of oral efficacy. Finally, exploration of the nature of the C-terminal
amino acid, with respect to its side-chain functionality and the carboxy
terminus, yielded a group of molecules that showed excellent in vitro potency for
inhibiting platelet aggregation, excellent integrin selectivity, a high level of
oral efficacy, and an extended duration of action.
PMID- 9651155
TI - Pharmacophores incorporating numerous excluded volumes defined by X-ray
crystallographic structure in three-dimensional database searching: application
to the thyroid hormone receptor.
AB - In the present study we investigate whether augmentation of pharmacophores with
excluded (ligand-inaccessible) volumes can condense the lengthy unspecific hit
lists often obtained in 3D-database searching. Our pharmacophores contained
hydrophobic features defined by the hormone, hydrogen bond donor and acceptor
features of the liganded rat THR-alpha X-ray structure, and excluded volumes
located at the positions and scaled according to the sizes of atoms delineating
the binding cavity. We now show, for the first time, that it is perfectly
feasible with the Catalyst software to search, in 1-2 h, medium-sized databases
such as Maybridge (with 5 x 10(5) compounds registered as multiple conformers)
with pharmacophores containing numerous (approximately 10(2)) excluded volumes.
The excluded volumes did not slow the search significantly; for pharmacophores
containing more features they also reduced the size of the hit list the most. For
example, with a 7-feature pharmacophore, the Maybridge hit list shrank from 4 to
1. The single remaining compound was subsequently shown to bind to THR-alpha with
an IC50 of 69 microM. Thus, we conclude that structure-based pharmacophores
augmented with numerous excluded volumes can effectively prune and focus hit
lists. The performance of multiple excluded volume-supplemented structure-based
pharmacophores in 3D-database mining as implemented with the Catalyst software
compares very favorably with other published procedures, with respect to speed,
specificity, and ease of use.
PMID- 9651156
TI - Heteroaryl analogues of AMPA. 2. Synthesis, absolute stereochemistry,
photochemistry, and structure-activity relationships.
AB - We have previously shown that (S)-2-amino-3-(3-hydroxy-5-phenyl-4
isoxazolyl)propionic acid [(S)-APPA, 2] is a weak agonist at (RS)-2-amino-3-(3
hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptors, specifically
activated by (S)-AMPA (1), whereas (S)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-4
isoxazolyl]propionic acid [(S)-2-Py-AMPA, 5] and (RS)-2-amino-3-[3-hydroxy-5-(2
thiazolyl)-4-isoxazolyl]propionic acid (4) are potent AMPA agonists. On the other
hand, (R)-APPA (3) and (R)-2-Py-AMPA (6) have been shown to be weak AMPA
antagonists. We now report the synthesis of 2-Py-AMPA (7a) and the isomeric
compounds 3-Py-AMPA (7b) and 4-Py-AMPA (7c) as well as the 7a analogues, (RS)-2
amino-3-[3-hydroxy-5-(6-methyl-2-pyridyl)-4-isoxazolyl]p ropion ic acid (7d) and
(RS)-2-amino-3-[3-hydroxy-5-(2-quinolinyl)-4-isoxazolyl]propionic acid (7e).
Furthermore, (RS)-2-amino-3-[3-hydroxy-5-(2-furyl)-4-isoxazolyl]propionic acid (2
Fu-AMPA, 7f) and its 5-bromo-2-furyl derivative (7g) were synthesized, and (S)-2
Fu-AMPA (8) and (R)-2-Fu-AMPA (9) were prepared by semipreparative chiral HPLC
resolution of 7f. HPLC analyses and circular dichroism spectroscopy indicated the
absolute stereochemistry of 8 and 9 to be S and R, respectively. This was
confirmed by an X-ray crystallographic analysis of 9.HCl. In receptor binding
(IC50 values) and rat cortical wedge electrophysiological (EC50 values) studies,
7c (IC50 = 5.5 +/- 0.6 microM; EC50 = 96 +/- 5 microM) was shown to be markedly
weaker than 7a (IC50 = 0.57 +/- 0.16 microM; EC50 = 7.4 +/- 0.2 microM) as an
AMPA agonist, whereas 7b,d,e were inactive. The very potent AMPA agonist effect
of 7f (IC50 = 0.15 +/- 0.03 microM; EC50 = 1.7 +/- 0. 2 microM) was shown to
reside exclusively in 8 (IC50 = 0.11 +/- 0.01 microM; EC50 = 0.71 +/- 0.11
microM), whereas 9 did not interact significantly with AMPA receptors, either as
an agonist or as an antagonist. 8 was shown to be photochemically active and is a
potential photoaffinity label for the recognition site of the AMPA receptors.
Compound 7g turned out to be a very weak AMPA receptor agonist (IC50 = 12 +/- 0.7
microM; EC50 = 160 +/- 15 microM). None of these new compounds showed detectable
effects at N-methyl-d-aspartic acid (NMDA) or kainic acid receptors in vitro. The
present studies have emphasized that the presence of a heteroatom in the 2
position of the heteroaryl 5-substituent greatly facilitates AMPA receptor
agonist activity.
PMID- 9651157
TI - Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)-1
Azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)oxime maleate
(CI-1017), a functionally m1-selective muscarinic agonist.
AB - The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one,
O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of
24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1
selective muscarinic agonist. Efficacy and m1 selectivity reside in the R
enantiomer, (R)-24Z (CI-1017).
PMID- 9651158
TI - Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4
(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full
agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl
ester (Zk 93423) at wild type and recombinant GABAA receptors.
AB - A pharmacophore and an alignment rule have previously been reported for BzR
agonist ligands. The design and synthesis of 6-(propyloxy)-4-(methoxymethyl)-beta
carboline-3-carboxylic acid ethyl ester (6-PBC, 24, IC50 = 8.1 nM) was based on
this pharmacophore. When evaluated in vivo this ligand exhibited
anticonvulsant/anxiolytic activity but was devoid of the muscle relaxant/ataxic
effects of "classical" 1,4-benzodiazepines (i.e., diazepam). Significantly, 6-PBC
24 also reversed diazepam-induced muscle relaxation in mice. The 3-substituted
analogues 40-46 and 48 of 6-PBC 24 and Zk 93423 27(IC50 = 1 nM) were synthesized
and evaluated in vitro to determine what affect these modifications would have on
the binding affinity at recombinant BzR subtypes. With the exception of the 3
amino ligands 40 and 41, all the beta-carbolines were found to exhibit high
binding affinity at BzR sites. The 3-propyl ether derivative 45 was also
evaluated in vivo and found to be devoid of any proconvulsant or anticonvulsant
activity at doses up to 40 mg/kg. The 6-(1-naphthylmethyloxy) and 6-octyloxy
analogues 25, 26, 28, and 29 of 6-PBC 24 were synthesized to further evaluate the
proposed alignment of agonists vs inverse agonists in the pharmacophore of the
BzR. In addition, ligands 26 and 29 were designed to probe the dimensions of
lipophilic pocket L3 at the agonist site. The activity of 29 was evaluated in
vivo; however, this analogue elicited no pharmacological effects at doses up to
80 mg/kg. These and other related beta-carbolines were also examined in five
recombinant GABAA receptor subtypes. Ligands 52-61 all exhibited moderate to high
affinity at GABAA receptors containing alpha1 subunits. These ligands will be
useful in further defining the pharmacophore at alpha1 beta3 gamma2 receptors.
PMID- 9651159
TI - Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from
SEAL similarity matrices.
AB - The program SEAL is suited to describe the electrostatic, steric, hydrophobic,
and hydrogen bond donor and acceptor similarity of different molecules in a
quantitative manner. Similarity scores AF can be calculated for pairs of
molecules, using either a certain molecular property or a sum of weighted
properties. Alternatively, their mutual similarity can be derived from distances
d or covariances c between SEAL-based property fields that are calculated in a
regular grid. For a set of N chemically related molecules, such values form an N
x N similarity matrix which can be correlated with biological activities, using
either regression analysis and an appropriate variable selection procedure or
partial least-squares (PLS) analysis. For the Cramer steroid data set, the test
set predictivities (r2pred = 0.53-0.84) of different PLS models, based on a
weighted sum of molecular properties, are superior to published results of CoMFA
and CoMSIA studies (r2pred = 0.31-0.40), regardless of whether a common alignment
or individual, pairwise alignments of all molecules are used in the calculation
of the similarity matrices. Training and test set selections have a significant
influence on the external predictivities of the models. Although the SEAL
similarity score between two molecules is a single number, its value is based on
the 3D properties of both molecules. The term 3D quantitative similarity-activity
analyses (3D QSiAR) is proposed for approaches which correlate 3D structure
derived similarity matrices with biological activities.
PMID- 9651160
TI - Homonojirimycin isomers and N-alkylated homonojirimycins: structural and
conformational basis of inhibition of glycosidases.
AB - A series of natural epimers of alpha-homonojirimycin and its N-alkylated
derivatives have been prepared to investigate the contribution of the different
chiral centers and conformation of the specificity and potency of inhibition of
glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin
(1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta
homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi
homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha
homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha
glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were
surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta
mannosidases but were moderately good as inhibitors of rice and some mammalian
alpha-glucosidases. Compound 4 was active in the micromolar range toward all
alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on
beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than
1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds
5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with
an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution
structure of 1 has been determined by X-ray diffraction and showed a chair
conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin)
predominantly equatorial to the piperidine ring in the crystal structure. This
preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR
coupling constants. The coupling constants for 7 suggest the axial orientation of
the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH
axial conformation appears to be responsible for more potent inhibition toward
processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed
that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the
inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive
against HIV-1 replication at 500 microg/mL as measured by inhibition of virus
induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl
1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was
37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha
glucosidase I than 1 and 8 both in vitro and in the cell culture system. These
data imply that inhibition of HIV by glycosidase inhibitors can be due to factors
other than simply inhibition of processing alpha-glucosidase I.
PMID- 9651161
TI - Carbocyclic analogues of the potent cytidine deaminase inhibitor 1-(beta-D
ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine).
AB - Three carbocylic analogues of the potent cytidine deaminase inhibitor (CDA)
zebularine [1-(beta-D-ribofuranosyl)-1, 2-dihydropyrimidin-2-one, 1a] were
synthesized. The selected pseudosugar templates correspond, respectively, to the
cyclopentenyl moiety of neplanocin A (compound 4), the cyclopentyl moiety of
aristeromycin (compound 5), and a newly designed, rigid bicyclo[3.1. 0]hexane
moiety (compound 6). These three carba-nucleoside versions of zebularine were
fashioned to overcome the inherent instability of the parent drug. Each target
compound was approached differently using either convergent or linear approaches.
The immediate precursor to the cyclopentenyl analogue 4 was obtained by a
Mitsunobu coupling of pseudosugar 7 with 2-hydroxypyrimidine. The cyclopentyl
analogue 5 was linearly constructed from carbocyclic amine 17, and the final
target 6 was similarly constructed from the carbobicyclic amine 27. Of the three
target compounds, only 5 showed a significant level of inhibition against human
CDA, but it was 16 times less potent than zebularine (Ki = 38 microM vs
Ki(apparent) = 2.3 microM). Although these carbocyclic analogues appeared to be
more stable than zebularine, replacement of the electronegative CO4' oxygen for
the less electronegative carbon in 4-6 presumably reduces the capacity of the
pyrimidin-2(1H)-one ring to form a covalent hydrate, a step considered crucial
for the compound to function as a transition-state inhibitor of the enzyme.
PMID- 9651162
TI - Synthesis and evaluation of peptidyl Michael acceptors that inactivate human
rhinovirus 3C protease and inhibit virus replication.
AB - Human rhinovirus, the chief cause of the common cold, contains a positive-sense
strand of RNA which is translated into a large polyprotein in infected cells.
Cleavage of the latter to produce the mature viral proteins required for
replication is catalyzed in large part by a virally encoded cysteine proteinase
(3Cpro) which is highly selective for -Q approximately GP- cleavage sites. We
synthesized peptidyl derivatives of vinylogous glutamine or methionine sulfone
esters (e.g., Boc-Val-Leu-Phe-vGln-OR: R = Me, 1; R = Et, 2) and evaluated them
as inhibitors of HRV-14 3C protease (3Cpro). Compounds 1 and 2 and several
related tetra- and pentapeptide analogues rapidly inactivated 3Cpro with
submicromolar IC50 values. Electrospray mass spectrometry confirmed the expected
1:1 stoichiometry of 3Cpro inactivation by 1, 2, and several other analogues.
Compound 2 also proved to be useful for active site titration of 3Cpro, which has
not been possible heretofore because of the lack of a suitable reagent. In
contrast to 1, 2, and congeners, peptidyl Michael acceptors lacking a P4 residue
have greatly reduced or negligible activity against 3Cpro, consistent with
previously established structure-activity relationships for 3Cpro substrates.
Hydrolysis of the P1 vinylogous glutamine ester to a carboxylic acid also
decreased inhibitory activity considerably, consistent with the decreased
reactivity of acrylic acids vs acrylic esters as Michael acceptors. Incorporating
a vinylogous methionine sulfone ester in place of the corresponding glutamine
derivative in 1 also reduced activity substantially. Compounds 1 and 2 and
several of their analogues inhibited HRV replication in cell culture by 50% at
low micromolar concentrations while showing little or no evidence of cytotoxicity
at 10-fold higher concentrations. Peptidyl Michael acceptors and their analogues
may prove useful as therapeutic agents for pathologies involving cysteine
proteinase enzymes.
PMID- 9651163
TI - Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel
class of tyrosine kinase inhibitors that exhibit selectivity toward particular
receptor tyrosine kinases.
AB - 3-Substituted indolin-2-ones have been designed and synthesized as a novel class
of tyrosine kinase inhibitors which exhibit selectivity toward different receptor
tyrosine kinases (RTKs). These compounds have been evaluated for their relative
inhibitory properties against a panel of RTKs in intact cells. By modifying the 3
substituted indolin-2-ones, we have identified compounds which showed selective
inhibition of the ligand-dependent autophosphorylation of various RTKs at
submicromolar levels in cells. Structure-activity analysis for these compounds
and their relative potency and selectivity to inhibit particular RTKs has
determined that (1) 3-[(five-membered heteroaryl ring)methylidenyl]indolin-2-ones
are highly specific against the VEGF (Flk-1) RTK activity, (2) 3-(substituted
benzylidenyl)indolin-2-ones containing bulky group(s) in the phenyl ring at the C
3 position of indolin-2-ones showed high selectivity toward the EGF and Her-2
RTKs, and (3) the compound containing an extended side chain at the C-3 position
of the indolin-2-one (16) exhibited high potency and selectivity when tested
against the PDGF and VEGF (Flk-1) RTKs. Recent published crystallographic data
for two of these 3-substituted indolin-2-ones provides a rationale to suggest
that these compounds may bind in the ATP binding pocket of RTKs. The structure
activity analysis supports the use of subsets of these compounds as specific
chemical leads for the development of RTK-specific drugs with broad application
for the treatment of human diseases.
PMID- 9651164
TI - Neurosteroid analogues. 6. The synthesis and GABAA receptor pharmacology of
enantiomers of dehydroepiandrosterone sulfate, pregnenolone sulfate, and
(3alpha,5beta)-3-hydroxypregnan-20-one sulfate.
AB - The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone
sulfate (2), and (3alpha,5beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4
6, respectively, were prepared by total steroid synthesis. The enantioselectivity
of the compounds as negative modulators of the GABAA receptors present in
cultured rat hippocampal neurons was examined using electrophysiological methods.
Enantioselectivity was found for the inhibitory actions of the
dehydroepiandrosterone enantiomers. The IC50s for compounds 1 and 4 were 11 +/- 1
and 80 +/- 14 microM, respectively. Little, if any, enantioselectivity was found
for the other two pairs of steroid sulfate inhibitors. The IC50s for compounds 2
and 5 were 82 +/- 12 and 76 +/- 27 microM, respectively. The IC50s for compounds
3 and 6 were 39 +/- 7 and 46 +/- 2 microM, respectively. The results suggest that
the sites of action for the androstane and pregnane series of steroid sulfate
blockers of GABA-mediated current are different. The observed enantioselectivity
for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory
actions are mediated via a chiral recognition site and provides new evidence in
support of the earlier hypothesis that there is a binding site for this compound
on GABAA receptors. Conversely, the failure to observe enantioselectivity for the
actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral
recognition site for these steroids does not exist on GABAA receptors and
suggests that the effects of these compounds on this receptor's function may
arise indirectly as a consequence of steroid-induced membrane perturbation.
PMID- 9651165
TI - Minimal-size, constrained corticotropin-releasing factor agonists with i-(i+3)
Glu-Lys and Lys-Glu bridges.
AB - In three earlier publications (Miranda et al. J. Med. Chem. 1994, 37, 1450-1459;
1997, 40, 3651-3658; Gulyas et al. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 10575
10579) we have hypothesized that covalent constraints such as side-chain-to-side
chain lactam rings would stabilize an alpha-helical conformation shown to be
important for the recognition and binding of the CRF C-terminus 30 residues, to
CRF receptors. These studies led to the discovery of useful CRF antagonists such
as alpha-helical CRF (alpha-hel-CRF) and Astressin both in vitro and in vivo. To
test the hypothesis that such lactam rings may also be modulating activation of
the receptor when introduced at the N-terminus of CRF, we studied the influence
of the successive introduction from residues 4 to 14 of a cyclo(i, i+3)[Lysi
Glu(i+3)] and a cyclo(i,i+3)[Glui-Lys(i+3)] bridge on the in vitro potency of the
agonist [Ac-Pro4,dPhe12,Nle21,38]hCRF(4-41) and related compounds. We have also
introduced the favored cyclo(Glu30-Lys33) substitution found to be remarkable in
several families of antagonists (such as Astressin) and in a number of CRF
agonists and investigated the role of residues 4-8 on receptor activation using
successive deletions. Earlier studies had shown that in both oCRF and alpha
helical CRF, deletion of residues 1-6, 1-7, and 1-8 led to gradual loss of
intrinsic activity (IA) (from 50% IA to <10% IA) resulting in alpha-hel-CRF being
a potent competitive antagonist. We show that acetylation of the N-terminus of
these fragments generally increases potency by a factor of 2-3 with no influence
on IA. While cyclo(30-33)[Ac-Leu8,dPhe12,Nle21, Glu30,Lys33,Nle38]hCRF(8-41) (30)
is the shortest reported analogue of CRF to be equipotent to CRF (70% IA), the
corresponding linear analogue (31) is 120 times less potent (59% IA). Addition of
one amino acid at the N-terminus ?cyclo(30-33)[Ac-Ser7,dPhe12,Nle21,
Glu30,Lys33,Nle38]hCRF(7-41) (28)? results in a 5-fold increase in agonist
potency and full intrinsic activity (113%). The most favored modifications were
also introduced in other members of the CRF family including sauvagine (Sau),
urotensin (Utn), urocortin (Ucn), and alpha-hel-CRF. Parallel and consistent
results were obtained suggesting that the lactam cyclization at residues 29-32
and 30-33 (for the members of the CRF family with 40 and 41 amino acid residues,
respectively) will induce (in the shortened agonists) a structural constraint
(alpha-helix) that stabilizes a bioactive conformation similar to that shown in
the Astressin family of CRF antagonists and that residue 8 (leucine or
isoleucine) bears the sole responsibility for activation of the receptor since
deletion of that residue leads to potent antagonists (Gulyas et al. Proc. Natl.
Acad.Sci. U.S.A. 1995, 92, 10575-10579).
PMID- 9651166
TI - Synthesis of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2, 3-benzodiazepin-4
ones as novel and potent noncompetitive AMPA receptor antagonists.
AB - A group of 7,8-(methylenedioxy)-1-phenyl-3,5-dihydro-4H-2, 3-benzodiazepin-4-ones
was synthesized and assayed for antagonism of rat brain alpha-amino-3-hydroxy-5
methylisoxazole-4-propionic acid (AMPA) receptors expressed in Xenopus oocytes.
The benzodiazepinones inhibited AMPA-activated membrane current responses in a
manner consistent with noncompetitive, allosteric inhibition of the receptor
channel complex. The most potent compound in the series was 1-(4-aminophenyl)-7,8
(methylenedioxy)-3,5-dihydro-4H-2, 3-benzodiazepin-4-one (6), which had an IC50
of 2.7 microM. For comparison, the reference compound GYKI 52466 (2) had an IC50
of 6.9 microM. Compound 6 also had potent anticonvulsant activity in a mouse
maximum electroshock-induced seizure (MES) assay: the ED50 was 2.8 mg/kg iv,
whereas the ED50 for GYKI 52466 was 4.6 mg/kg iv. In contrast to a previous
report, the 7,8-dimethoxy analogue of 6 was a low-potency AMPA antagonist (IC50
>100 microM) and weak anticonvulsant (ED50 >10 mg/kg iv). The benzodiazepinones
described herein are potent noncompetitive AMPA receptor antagonists that could
have therapeutic potential as anticonvulsants and neuroprotectants.
PMID- 9651167
TI - In vitro platelet-activating factor receptor binding inhibitory activity of
pinusolide derivatives: a structure-activity study.
AB - Pinusolide, a labdane-type diterpene lactone isolated from Biota orientalis, was
found to be a potent platelet-activating factor (PAF) receptor binding
antagonist. To investigate the structure-activity relationship and find
derivatives with improved pharmacological profiles, 17 pinusolide derivatives
were prepared and tested for their ability to inhibit the PAF receptor binding.
The results demonstrated that the carboxymethyl ester group at C-19, the
integrity of the alpha,beta-unsaturated butenolide ring, and the exocyclic
olefinic function of pinusolide are all necessary for its maximum PAF receptor
binding inhibitory activity. Among the derivatives, the 17-nor-8-oxo derivative 8
was found to be as potent as pinusolide. The results also suggested that several
derivatives warrant further pharmaceutical and pharmacological studies due to
their improved water solubility (8 and 11) and apparent lack of susceptibility to
Michael-type nucleophilic addition (13 and 18).
PMID- 9651169
TI - Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase.
AB - Nitric oxide (NO.) is an important biomodulator of many physiological processes.
The inhibition of inappropriate production of NO. by the isoforms of nitric oxide
synthase (NOS) has been proposed as a therapeutic approach for the treatment of
stroke, inflammation, and other processes. In this study, certain 2-nitroaryl
substituted amino acid analogues were discovered to inhibit NOS. Analogues
bearing a 5-methyl substituent on the aromatic ring demonstrated maximal
inhibitory potency. For two selected inhibitors, investigation of the kinetics of
the enzyme showed the inhibition to be competitive with l-arginine. Additionally,
functional NOS inhibition in tissue preparations was demonstrated.
PMID- 9651168
TI - Synthesis and biological activity of a novel methylamine-bridged enkephalin
analogue (MABE): a new route to cyclic peptides and peptidomimetics.
AB - The synthesis and biological activity of a methylamine-bridged enkephalin
analogue (MABE) is presented. The key step in the synthesis of the target
compound involves the ring opening of Cbz-d-serine beta-lactone with Boc-Phe
NHCH2CH2NHCH3. Further synthetic elaboration of the resulting building block
yielded compound 1 (MABE, Tyr-c[(NbetaCH3)-D-A2pr-Gly-Phe-NHCH2CH2-], where A2pr
is a 2,3-diaminopropionic acid residue). Utilizing a combination of NMR and
molecular modeling, the structure-biological activity relationships for compound
1 were studied. Using an in vitro isolated receptor assay, MABE was found to have
affinities for isolated mu delta, and kappa opioid receptors of 1.6, 2.1, and 340
nM, respectively. By an in vivo thermal escape assay, MABE was found to have an
ED50 of 0.027 microg in the rat when administered intrathecally. This effect was
reversed by naloxone. By comparison, DAMGO, morphine, and DPDPE were found to
yield ED50 values of 0.14, 2.4, and 54 microg, respectively, in the same assay.
PMID- 9651170
TI - Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective
antagonist that inhibits phenylephrine-induced contraction of the human prostate.
AB - A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3
(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1
yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned
human alpha adrenoceptors as well as the rat L-type calcium channel. Within this
compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3
((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed
good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73)
and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the
human prostate.
PMID- 9651171
TI - N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase.
AB - Inhibitors of Ras protein farnesyltransferase are described which are reduced
pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that
signals farnesylation. Reduction of the carbonyl groups linking the first three
residues of the tetrapeptide leads to active inhibitors which are chemically
unstable. Stability can be restored by alkylating the central amine of the
tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with
concomitant modification of the side chain of the third residue led to 2(S)-(2(S)
?[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)- methylpentyl]naphthalen-1
ylmethylamino?acetylamino)-4 -methylsulfany lbutyric acid (11), a subnanomolar
inhibitor. The methyl ester (10) of this compound exhibited submicromolar
activity in the processing assay and selectively inhibited anchorage-independent
growth of Rat1 cells transformed by v-ras at 2.5-5 microM.
PMID- 9651173
TI - Matching scientific with societal interests: charges for the new editor.
PMID- 9651172
TI - 14-Desoxy analogues of naltrindole and 7-spiroindanyloxymorphone: the role of the
14-hydroxy group at delta opioid receptors.
AB - The 14-hydroxy group is known to increase the antagonist potency of mu-selective
opioid ligands. To investigate the role of this group at the delta opioid
receptor, the 14-desoxy analogues (7 and 9) of the delta-selective ligands,
naltrindole (1, NTI) and spiroindanyloxymorphone (2, SIOM), have been synthesized
and tested. The in vitro pharmacologic activities of 7 and 9 suggest that the 14
hydroxy group plays an important role in determining the delta selectivity and
potency of NTI and SIOM.
PMID- 9651174
TI - Assessment of activation, differentiation, and carcinogenesis of lung cells by
quantitative competitive RT-PCR.
PMID- 9651175
TI - Expression measurement of many genes simultaneously by quantitative RT-PCR using
standardized mixtures of competitive templates.
AB - Progress toward complete sequencing of all human genes through the Human Genome
Project has already resulted in a need for methods that allow quantitative
expression measurement of multiple genes simultaneously. It is increasingly
recognized that relative measurement of multiple genes will provide more
mechanistic information regarding cell pathophysiology than measurement of
individual genes one by one or by methods that do not allow direct intergene
comparison. In this study, previously described quantitative reverse
transcription-polymerase chain reaction methods were modified in an effort to
provide a rapid, simple method for this purpose. Internal standard competitive
templates (CTs) were prepared for each gene and were combined in a single
solution containing CTs for more than 40 genes at defined concentrations relative
to one another. Any subsequent dilution of the CT mixture did not alter the
relationship of one CT to another. Because the same CT standard solution or a
dilution of it was used in all experiments, data obtained from different
experiments were easily compared. The use of multiple CT mixtures with different
housekeeping gene to target gene ratios provided a linear dynamic range spanning
the range of expression of all genes thus far evaluated. CT stock solutions were
used to simultaneously quantify the expression of 25 genes relative to beta-actin
and glyceraldehyde-3-phosphate dehydrogenase in normal and malignant bronchial
epithelial cells. Because the CT concentrations were known, data in the form of
both absolute messenger RNA (mRNA) copy number and mRNA relative to housekeeping
gene mRNA were obtained. The methods and reagents described will allow rapid,
quantitative measurement of multiple genes simultaneously, using inexpensive and
widely available equipment. Furthermore, the CT standard solution may be
distributed to other investigators for interlaboratory standardization of
experimental conditions.
PMID- 9651176
TI - The gene expression index c-myc x E2F-1/p21 is highly predictive of malignant
phenotype in human bronchial epithelial cells.
AB - Recent methodological developments allow expression measurement of many genes
simultaneously, thereby revealing patterns of gene expression that can be related
to phenotype. We hypothesized that through the use of such methods we could
identify patterns of gene expression associated with the malignant phenotype in
human bronchial epithelial cells (BEC). To test this hypothesis, a recently
developed quantitative reverse transcriptase polymerase chain reaction method was
used to assess simultaneously expression of 15 genes mechanistically associated
with cell-cycle control (c-myc, E2F-1, p21, rb, PCNA, cyclin D2, cyclin D3,
cyclin E, cdc2, CDK2, CDK4, mad, max p21, max p22, and p53) in normal cell
cultures from five individuals and in nine different malignant BEC lines.
Relative to the mean expression levels in cultured normal cell populations,
expression of c-myc, E2F-1, PCNA, cyclin E, and CDK4 messenger RNA (mRNA) were
significantly increased and expression of p21 and p53 mRNA were significantly
decreased in one or two, but not all three subtypes (squamous, adenocarcinoma and
small cell) of carcinoma cell lines evaluated. No single cell-cycle control gene
discriminated all three subtypes from normal cell populations. In contrast, the
gene expression index c-myc x E2F-1/p21 separated all carcinoma cell lines from
all normal cell populations initially evaluated. This malignancy index was
validated in an additional three cultured normal BEC and three carcinoma cell
lines, as well as three pairs of matched primary normal bronchial epithelial and
primary bronchogenic carcinoma samples, and three pairs of matched primary normal
lung parenchyma and primary bronchogenic carcinoma tissue. Again, the c-myc x E2F
1/ p21 index successfully discriminated all cultured and primary normal from
malignant samples and thereby had a predictive value of 1 (no false positives and
no false negatives). We hypothesize that because of functional mutations in cell
cycle regulatory genes (e.g., p53 and/or rb), cells lose the ability to maintain
a pattern of gene expression mechanistically associated with normal, division
limited homeostatic equilibrium. Because the c-myc x E2F-1/p21 gene expression
index has high specificity for malignant tissue, it will allow confirmation that
there is a significant amount of tumor tissue present in small (e.g., fine
needle) biopsy specimens prior to evaluating them for expression of other genes,
such as those involved in chemoresistance or radioresistance. In addition, the
goal of most gene therapy efforts is to alter levels of gene expression
quantitatively. This index and others derived in a similar manner may better
define potential gene therapy targets as well as response of targeted genes to
therapy.
PMID- 9651177
TI - Loss of spr1 expression measurable by quantitative RT-PCR in human bronchogenic
carcinoma cell lines.
AB - Expression of the small, proline-rich protein (spr1) squamous differentiation
marker was measured in five cultured normal and 12 malignant human bronchial
epithelial cell (BEC) populations by quantitative reverse transcriptase
polymerase chain reaction (RT-PCR). Whereas spr1 expression was quantifiable and
inducible in all five cultured normal cell populations, in all 12 carcinoma cell
lines evaluated it was neither quantifiable nor inducible. Primers spanning the
entire spr1 coding sequence amplified full-length PCR product from genomic DNA;
therefore, large deletions in the coding region were not responsible for the loss
of expression measurable by RT-PCR. This is the first molecular genetic marker
reported that distinguishes all normal from all carcinoma cell populations
evaluated. Because the spr1 protein is a component of the crosslinked envelope
that forms during the squamous differentiation process, we hypothesize that the
apparent loss of spr1 gene expression disrupts mechanisms for terminal squamous
differentiation in the bronchial epithelium, thereby contributing to malignant
transformation.
PMID- 9651178
TI - MUC5B and MUC7 are differentially expressed in mucous and serous cells of
submucosal glands in human bronchial airways.
AB - Mucins are high molecular-weight glycoproteins involved in the protection and
lubrication of respiratory, gastrointestinal, and reproductive tracts.
Hypersecretory diseases such as cystic fibrosis (CF), chronic bronchitis, and
asthma result in dysregulated levels of mucin production stemming from increased
abundance of mucin-secreting cell types in the surface airway epithelium and
submucosal glands. The isolation of at least nine mucin genes has prompted
studies to characterize the cellular expression patterns of these mucins in
normal and diseased tissues. In the present study, in situ hybridization and
immunocytochemical methods were used to determine the cellular distribution of
MUC5B and MUC7 expression in CF and non-CF human bronchus. Our findings indicate
that MUC5B and MUC7 have expression patterns in human bronchial airways that are
limited exclusively to submucosal glands. Specifically, MUC5B expression was
confined to all mucous tubules, whereas MUC7 expression was seen in a subset of
lysozyme expressing serous tubules of submucosal glands. Interestingly,
heterogeneity of MUC7 expression between glands of the same bronchus ranged from
0 to 93% of serous tubules, suggesting that functional diversity may exist
between glands within the same bronchial sample. No remarkable differences were
observed in the expression patterns of MUC5B or MUC7 between CF (n = 7) and non
CF (n = 10) bronchial samples. In conclusion, MUC5B and MUC7 expressions define
different cellular compartments within submucosal glands of human bronchus and
lend insight into the heterogeneity of mucin production in the lung.
PMID- 9651179
TI - Induction, duration, and resolution of airway goblet cell hyperplasia in a murine
model of atopic asthma: effect of concurrent infection with respiratory syncytial
virus and response to dexamethasone.
AB - We recently described a murine model of atopic asthma in which a marked,
extensive hyperplasia of airway goblet cells is induced by repeated challenge of
ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J.
Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the
duration of this feature and of its spontaneous resolution in the absence of
further allergen exposure. Induction of severe neutrophilic inflammation in the
airways by repeated intratracheal administration of lipopolysaccharide failed to
induce goblet cell hyperplasia (GCH) to as great a degree as that induced by
allergen, suggesting that nonallergic inflammation is a relatively poor inducer
of this phenotype change in mice. When a "subclinical" infection of the lungs
with the human A2 strain of respiratory syncytial virus was superimposed on the
model of atopic asthma, recruitment of monocytes and lymphocytes to the airways
was enhanced and a discharge of goblet cell mucin contents was observed. This may
partly explain the respiratory difficulty that typifies virally induced
exacerbations of asthma in humans. Daily systemic treatment of sensitized mice
with dexamethasone during the period of allergen challenge produced a dose
related suppression of developing GCH, while similar treatment during the period
following the establishment of extensive hyperplasia induced an accelerated
resolution toward a normal epithelial phenotype. These results confirm and extend
the relevance of this model as a representation of the human disease.
PMID- 9651180
TI - Enhanced expression of GM-CSF in differentiating eosinophils of atopic and atopic
asthmatic subjects.
AB - Higher numbers of eosinophil/basophil colony-forming units (Eo/B CFU) are
observed in blood of atopic individuals, and can be enhanced in atopic asthmatics
by allergen-inhalation challenge. It is known that mature basophils and
eosinophils synthesize cytokines relevant to allergic inflammation. To
investigate the potential role of growth factors in allergic disease we examined
the expression of the hemopoietic cytokines, granulocyte-macrophage colony
stimulating factor (GM-CSF) and interleukin (IL)-5, in differentiating Eo/B
colony cells from normal and atopic individuals, and from atopic asthmatics
before and after allergen-inhalation challenge. Peripheral blood was collected
from two normal and 12 atopic individuals, and also from 25 atopic asthmatics
before and 24 h after allergen challenge. Nonadherent mononuclear cells were
isolated and grown in semisolid growth medium. Eo/B colonies were selected and
cytospins were prepared for immunocytochemical analysis of colony cells. Eo/B
colonies, especially carbol chromotrope 2R+ cells, selected at Days 10, 14, and
18 from atopic donors contained messenger RNA for GM-CSF by combined in situ
reverse transcription-polymerase chain reaction and cytochemistry, and
demonstrated time-dependent expression of GM-CSF by immunocytochemistry (P =
0.007). Atopic individuals demonstrated a higher percentage of cells expressing
GM-CSF than did normal subjects under all growth conditions when examined at Day
14 (P = 0. 04). Atopic asthmatics challenged with inhaled allergen who
demonstrated a dual airway response, an increase in the number of blood
eosinophils (P = 0.0001), and an increase in the number of Eo/B CFU (P = 0.02)
also demonstrated a significant increase in the percentage of colony cells
expressing immunostainable GM-CSF (P = 0. 0009), but only a variable effect on
those expressing IL-5, 24 h after allergen. These results suggest that GM-CSF
expression by differentiating Eo/Bs may provide an additional stimulus in vivo to
enhance Eo/B progenitor differentiation in atopic and asthmatic individuals,
especially after allergen challenge. The concept of microenvironmental
differentiation, where blood progenitor cells may aid in their own
differentiation, is supported by these ex vivo findings.
PMID- 9651181
TI - Modulation of glucose transport in fetal rat lung: a sexual dimorphism.
AB - Male fetuses exhibit delayed lung maturation and surfactant production in
comparison with female fetuses. This delay may be related to sex hormone effects:
estrogen enhances and androgens delay lung development. The uptake of glucose, an
important precursor for surfactant synthesis, may be differently affected by
estrogen and androgens. In these studies we determined the effects of these two
hormones on glucose transport (glucose uptake, glucose transporter [Glut] 1
protein, and mRNA) and hexokinase activity in lung tissue of fetal rats. On Day
20 of gestation (term = 21.5 d) lung tissue was harvested from female and male
fetal rats, minced into explants, and cultured for 24 h. Basal glucose uptake,
measured in the absence of sex hormones, was 37% higher (P < 0.05) in female
compared with male lungs. Explants were washed and cultured for an additional 3 h
or 24 h in either estradiol or dihydrotestosterone (DHT) at 0, 1, 10, or 100 nM.
Twenty-four-hour treatment with estradiol in both male and female explants
increase 2-deoxyglucose uptake, Glut 1 protein, and mRNA levels (P < 0.05).
However, explants from male fetuses were not as responsive to estradiol treatment
as were those from females (P < 0.05). Treatment for 24 h with DHT decreased 2
deoxyglucose uptake, Glut 1 protein, and mRNA levels in females and males (P <
0.05). There was no difference in response between females and males. Short-term
incubation (3 h) with sex hormones had no effect on glucose uptake. However, 3-h
treatment with estradiol did increase Glut 1 mRNA levels (P < 0.05). Hexokinase
activity was not affected by estradiol or DHT treatment. These findings indicate
that estradiol and DHT differentially regulate glucose uptake in fetal rat lung
tissue. This regulation of substrate supply (glucose) by estradiol and DHT may be
another mechanism for the sexual dimorphism observed in lung development and
surfactant synthesis.
PMID- 9651182
TI - A correlation between epithelial proliferation rates, basement membrane component
localization patterns, and morphogenetic potential in the embryonic mouse lung.
AB - Lung epithelial branching morphogenesis results from a repetitive series of cleft
and bud formation, a process dependent upon a complex interaction with the
surrounding mesenchyme. The present study describes these cleft- and bud-forming
regions as autonomous morphogenetic compartments within the embryonic day 11.5
(E11.5) mouse lung and directly correlates their identity with differences in
epithelial proliferation rates and the localization pattern of specific basement
membrane components. Lung buds were cultured in vitro, in two-dimensional planes,
and labeled with a series of 5-bromo-2'-deoxyuridine (BrdU) pulses. Collectively,
epithelial cells within actively budding regions of the bronchiolar tree
demonstrated an at least 2.5-fold greater proliferation rate than those situated
in the adjacent cleft-forming regions. Epithelial proliferation rates showed an
inverse relationship with the degree of immunoreactivity of nidogen, laminin-1,
fibronectin, and collagen IV within the underlying basement membrane. Epithelial
cells dissected free from mesenchyme demonstrated cell-cell contact-dependent
proliferation, thus revealing a hierarchy between mesenchymal signaling and
direct epithelial cell-cell communication during branch formation. Dissection of
the E11.5 bronchiolar tree into specific distalbud and interbud regions and their
in vitro culture demonstrated differences in their autonomous morphogenetic
potential. Tissue dissected from the distal tips of the lung continued to branch,
whereas tissue dissected from immediately adjacent cleft regions seldom branched.
Isolated distalbud tissue also continued to correlate regional differences in
epithelial proliferation rates and immunolocalization patterns of nidogen,
laminin-1, fibronectin, and collagen IV with branch formation. These results
support the basement membrane remodeling hypothesis, thus connecting nidogen,
collagen type IV, fibronectin, and laminin-1 localization with the molecular
processes directing epithelial proliferation and supporting bud outgrowth and
cleft formation/stabilization during lung morphogenesis.
PMID- 9651183
TI - Localization of Staphylococcus aureus in infected airways of patients with cystic
fibrosis and in a cell culture model of S. aureus adherence.
AB - Staphylococcus aureus causes chronic respiratory tract infections in patients
with cystic fibrosis (CF). Using immunofluorescence and scanning and transmission
electron microscopy we located S. aureus in lung specimens of three infected CF
patients, in a nasal polyp of one CF patient, and in a suspension cell culture
system of primary nasal epithelial cells in vitro. Very little of S. aureus was
attached to the lung epithelium, whereas abundant S. aureus was detectable in the
mucus of obstructed airways. Similarly, S. aureus adhered to components of
secreted mucus on primary nasal epithelial cells of CF patients and healthy
control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/
1.5; controls: 22. 0 +/- 5.8). Mucus depletion of cell balls prior to incubation
with S. aureus resulted in a significantly reduced binding (bacteria/cell +/- SD:
CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0. 007). Binding of S.
aureus to cell balls from CF patients or control subjects did not differ
significantly. When cell balls were treated with human neutrophil elastase,
hypersecretion caused removal of S. aureus from cell-associated mucus. The
results suggest that S. aureus adheres primarily to mucus components of the
respiratory epithelium and that significant differences do not exist in binding
of S. aureus to CF or non-CF cells.
PMID- 9651184
TI - Expression of the high-affinity receptor for IgE on bronchial epithelial cells of
asthmatics.
AB - Bronchial epithelial cells are the first cells to come into contact with inhaled
pneumoallergens. It has been suggested that these cells may play an important
role in the allergic response, and indeed bronchial epithelial cells of some
atopic asthmatic subjects have been shown to express the low-affinity receptor
for IgE on their surface. In this report we demonstrate, using bronchial
biopsies, that bronchial epithelial cells of some asthmatic subjects express both
the alpha and gamma chains of the high-affinity receptor for IgE (Fcepsilon RI)
on their surface and that they are capable of fixing IgE. Second, using reverse
transcription-polymerase chain reaction, we show that both control and asthmatic
subjects have messenger RNA for Fcepsilon RI. Finally, we demonstrate that this
receptor may be functional since stimulation of the cells with the antibody to
the alpha chain of Fcepsilon RI results in the liberation of 15
hydroxyeicosatetraenoic acid from epithelial cells of asthmatic, but not control,
subjects or subjects suffering from chronic bronchitis. These data suggest that
bronchial epithelial cells from at least some asthmatic subjects express a
functional high-affinity receptor for IgE and it is therefore possible that these
cells may be able to interact directly with inhaled allergens.
PMID- 9651185
TI - Air pollution particles induce IL-6 gene expression in human airway epithelial
cells via NF-kappaB activation.
AB - Fine particles in the air have been associated with increased mortality and
morbidity. Particulate air pollution is a complex mixture which varies by region
and includes a number of components including residual oil fly ash (ROFA), a
byproduct of power plant and industry fuel-oil combustion. Human airway
epithelial cells exposed to ROFA release inflammatory cytokines including
interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is
dependent upon pretranscriptional binding of cis regulatory elements, including
nuclear factor kappaB (NF-kappaB). To investigate the role of NF-kappaB in the
particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS
2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6
messenger RNA (mRNA), which was preceded by the activation of nuclear proteins
binding to the NF-kappaB sequence motif in the IL-6 promoter. Transient
transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked
to a luciferase reporter gene confirmed that NF-kappaB binding is necessary for
the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal
chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine,
suggesting that the activation of NF-kappaB may be mediated through reactive
oxygen intermediates generated by transition metals found in ROFA. Activation of
NF-kappaB may therefore be a critical first step in the inflammatory cascade
following exposure to particles generated by oil combustion.
PMID- 9651186
TI - Identification of a novel alternatively spliced mRNA of murine pulmonary
surfactant protein B.
AB - An alternatively spliced mRNA of pulmonary surfactant protein B (SP-B) was
identified in murine lung. Sequencing analysis revealed a 69 base-pair (bp)
deletion at the beginning of exon 7 of SP-B, presumably the result of an
alternative splicing event. Reverse transcription-polymerase chain reaction (RT
PCR) of mouse, rat, and rabbit lung RNA revealed the existence of full-length and
the 69-bp deleted short form. Ribonuclease protection assay of the SP-B messenger
RNA (mRNA) demonstrated expression of both isoforms in five strains of adult and
fetal mice with different genetic backgrounds, as well as in rabbit, but not in
human. Splice junction sequences in exon 6 and at the exon 7 splice boundary for
the two isoforms are similar, including AG doublet identity, but sequence
differences do not account for species variation in isoform abundance. The
abundance of the short SP-B mRNA isoform was approximately 30% of total SP-B mRNA
in mouse and rabbit. Analysis of precursor SP-B protein in mouse lung suggested
that the two mRNA species are expressed as stable protein isoforms.
PMID- 9651187
TI - Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity.
AB - Recent studies have shown that homozygous Mn superoxide dismutase (Sod2) gene
knockout mice (Sod2(-/-)) die shortly after birth with extensive myocardial
injury, whereas heterozygous mutants (Sod2(+/-)) are phenotypically normal in
room air. In the current study, we showed that Sod2(+/-) mice with approximately
50% of normal pulmonary MnSOD activity and normal levels of lung CuZnSOD,
catalase, and glutathione peroxidase activities were not substantially more
susceptible to 100% O2 toxicity than their normal Sod2(+/+) littermates. The mean
(+/- SD) survival of Sod2(+/-) mice in 100% O2 was 101.4 +/- 14.8 h (n = 20)
versus 103.2 +/- 11.3 h (n = 20) for Sod2(+/+) littermates (P > 0.60). In
addition, Sod2(+/-) mice with approximately 50% of normal heart MnSOD activity
and Sod2(+/+) mice did not develop any ultrastructural abnormalities in the
myocardium at 75 h or 90 h after 100% O2 exposure. These results suggest that in
mice, only 50% of MnSOD activity may be sufficient for normal resistance to 100%
O2 toxicity.
PMID- 9651188
TI - Tissue sources of cytochrome P450 4A and 20-HETE synthesis in rabbit lungs.
AB - We previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE) is an
endogenous cytochrome P450 (cP450) 4A metabolite of arachidonic acid (AA) in
human lung tissue, and is a potent cyclooxygenase-dependent vasodilator of
isolated pulmonary arteries. In the present investigations, we identified sources
of cP450 4A immunospecific protein, messenger RNA (mRNA), and 20-HETE synthesis
in rabbit lungs. Microsomes of peripheral lung tissue, airways, small and large
vessels, and lysates of alveolar macrophages all express proteins of
approximately 50 kD which cross-reacted with a primary antibody raised against
rat liver cP450 4A1. Peripheral lung tissue, small and large pulmonary arteries,
airways, and isolated vascular smooth muscle cells from small pulmonary arteries
produced 20-HETE when incubated with AA. Expression of cP450 4A6/4A7 mRNA was
readily detectable by reverse transcription-polymerase chain reaction using
isoform-specific probes and 5 microg total RNA extracted from microdissected
small pulmonary arteries. These data demonstrate that small pulmonary arteries
express cP450 4A proteins and vascular smooth muscle cells derived from these
arteries synthesize 20-HETE. Furthermore, cP450 4A appears to be widely
distributed in rabbit tissue, raising the possibility that 20-HETE generated from
nonvascular tissue could serve as a paracrine factor in the pulmonary
circulation.
PMID- 9651189
TI - Prolonged cell-cycle arrest associated with altered cdc2 kinase in monocrotaline
pyrrole-treated pulmonary artery endothelial cells.
AB - Monocrotaline pyrrole (MCTP), a metabolite of the pyrrolizidine alkaloid
monocrotaline, is thought to initiate damage to pulmonary endothelial cells
resulting in delayed but progressive pulmonary interstitial edema, vascular wall
remodeling, and increasing pulmonary hypertension. MCTP was previously shown to
inhibit pulmonary endothelial cell proliferation and cause cell-cycle arrest in
vitro. To determine the persistence of arrest and better characterize the cell
cycle stage at which it occurs, bovine pulmonary artery endothelial cells (BPAEC)
under differing growth conditions were exposed to low (5 microg/ml) or high (34.5
microg/ml) concentrations of MCTP for varying times. Flow cytometric cell-cycle
analysis was coupled with Western blot and biochemical analysis of cdc2 kinase
and measurements of cell size. MCTP treatment induced a G2 + M phase arrest in 48
h exposed confluent BPAEC that persisted for at least 28 d and was associated
with continued cellular enlargement. A short-duration MCTP exposure of confluent
(low and high concentration) and log phase (high concentration) BPAEC caused
persistent cell-cycle arrest for 1 wk, whereas a low-concentration exposure in
log phase cells resulted in cell-cycle arrest with reversal 96 h after exposure.
Western blot examination revealed that by 24 h of MCTP exposure, the
phosphorylation state of cdc2 was consistent with the inactive form of the kinase
(confirmed by biochemical assay); this alteration persisted through at least 96 h
of exposure. We conclude that MCTP induces a progressive irreversible endothelial
cell dysfunction leading to inactivation of cdc2 kinase and irreversible cell
cycle arrest at the G2 checkpoint.
PMID- 9651190
TI - Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a
water channel or a regulator of aquaporin-type water channels.
AB - T1alpha is a protein of unknown function that is expressed at the plasma membrane
in epithelia involved in fluid transport, including type I alveolar epithelial
cells, choroid plexus, and ciliary epithelium. The purpose of this study was to
test the hypothesis that T1alpha functions as a water channel or a regulator of
aquaporin-type water channels that are coexpressed with T1alpha. Two
complementary DNAs (cDNAs) (hT1alpha-1 and hT1alpha-2) encoding human isoforms of
T1alpha were cloned by homology to the rat T1alpha coding sequence. The cDNAs
encoded 164 (hT1alpha-1) and 162 (hT1alpha-2) amino acid proteins with high
homology to rat T1alpha in a putative membrane-spanning domain. hT1alpha-1
transcripts of 2. 6 and 1.4 kb were detected in human lung, heart, and skeletal
muscle, and a single hT1alpha-2 transcript of 1.2 kb was detected in human lung.
Rat and mouse T1alpha were isolated by reverse transcription-polymerase chain
reaction and confirmed by DNA sequence analysis. Expression of mouse, rat, and
human T1alpha isoforms in Xenopus oocytes did not increase osmotic water
permeability (Pf) above that in water-injected oocytes, nor was there an effect
of protein kinase A or C activation; Pf was increased > 10-fold in positive
control oocytes expressing aquaporin (AQP)1 or AQP5. Coexpression of AQP1 or AQP5
with excess T1alpha gave Pf not different from that in oocytes expressing AQP1 or
AQP5 alone. Oocyte plasma membrane localization of epitope-tagged T1alpha protein
was confirmed and quantified by immunoprecipitation of microdissected plasma
membranes. Quantitative densitometry indicated that the single-channel water
permeability of T1alpha is under 2 x 10(-16) cm3/s, suggesting that T1alpha is
not involved in the high transalveolar water permeability in intact lung. The
cloning of hT1alpha isoforms may permit the development of an assay of type I
cell antigen in airspace fluid as a marker of human lung injury.
PMID- 9651191
TI - Platelet-activating factor mediates intercellular adhesion molecule-1-dependent
radical production in the nonhypoxic ischemia rat lung.
AB - It has been reported that reperfusion is the most important factor in ischemia
reperfusion (I/R) injury. However, causes of I/R injury in the lung are
controversial, because oxygen is always supplied if ventilation continues.
Therefore, we hypothesized that nonhypoxic ischemia without reperfusion is
sufficient for lung injury. To test our hypothesis, we measured both hydrogen
peroxide (H2O2) production in the pulmonary circulation, by digital imaging
fluorescent dichlorofluorescein, and microvascular permeability (MVP), by the
Evans blue extravasation technique in the nonhypoxic ischemia rat lung. We made a
nonhypoxic ischemia rat lung by clamping the left pulmonary artery. Both H2O2
production and MVP increased in the nonhypoxic ischemia rat lung. We also
determined the effect of oxygen removal by clamping the bronchus in advance of
pulmonary artery occlusion, intercellular adhesion molecule-1 (ICAM-1)
neutralization with monoclonal antibody 1A29, and platelet-activating factor
(PAF) receptor antagonist CV6209 on H2O2 production and MVP. These treatments
inhibited both H2O2 production and MVP increase. At high-power viewing of the
fluorescent dichlorofluorescein image, H2O2 was detected in the leukocytes within
pulmonary capillaries. These data indicate that the nonhypoxic ischemia without
reperfusion alone causes radical production and increases MVP. Furthermore, PAF
and ICAM-1 contribute to these reactions.
PMID- 9651192
TI - Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1
activation of eosinophil function.
AB - Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
(VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on
vascular endothelium and important in the development of eosinophil (EOS)
accumulation in allergic inflammation. To define the role of these adhesion
proteins in EOS inflammation, peripheral blood EOS from allergic donors were
incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM
1-coated plates, and the effects of these adhesion proteins on EOS effector
functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS
adhesion to ICAM-1 required a second signal, such as granulocyte macrophage
colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS
superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the
reactions resulted in a greater and equivalent production of O2- with VCAM-1 and
ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release
of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted
calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced
O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1
were significantly inhibited by anti-beta2-integrin antibody. These results
suggest that ICAM-1 and VCAM-1 are important in determining the eventual function
of airway EOS.
PMID- 9651193
TI - Granulocyte colony-stimulating factor induces neutrophil sequestration in rabbit
lungs.
AB - The effects of intravenous injection of recombinant human granulocyte colony
stimulating factor (rhG-CSF) on circulating neutrophil numbers, pulmonary
vascular permeability, and morphologic changes in the lung were examined in
rabbits. Intravenous injection of rhG-CSF caused a rapid, profound neutropenia
due to neutrophil sequestration primarily within capillaries but also in larger
microvessels of the lungs. Examination of neutrophil deformability using
microfilters revealed that granulocyte colony-stimulating factor (G-CSF)
treatment caused a rapid stiffening of neutrophils through the polymerization of
F-actin but not microtubule assembly. The expression of CD11b, CD11c, and CD18 on
human neutrophils after G-CSF treatment increased, but CD11a did not. Intravenous
injection of rhG-CSF did not induce neutrophil emigration or albumin leakage into
alveolar space, wet/dry lung weight ratios were unchanged, and no pathologic
changes in lung histology were observed. These studies indicate that injection of
rhG-CSF caused a rapid neutropenia and neutrophil sequestration in the lungs that
is likely to be mediated through a G-CSF-induced decrease in neutrophil
deformability, although neutrophil-endothelial cell adhesion may also play a
role. However, this G-CSF-induced neutrophil sequestration did not induce a
massive lung injury.
PMID- 9651194
TI - Contribution of subsaturating GABA concentrations to IPSCs in cultured
hippocampal neurons.
AB - The time course of EPSCs and IPSCs is at least partly determined by the
concentration profile of neurotransmitter acting on postsynaptic receptors.
Several recent reports have suggested that the peak synaptic cleft concentration
of the inhibitory neurotransmitter GABA likely reaches at least 500 microM, a
level that saturates the GABAA receptor. In the course of investigating the
experimental anticonvulsant 3,3-diethyl-2-pyrrolidinone (diethyl-lactam), we have
observed an important contribution to IPSC decay by subsaturating concentrations
of GABA. Diethyl-lactam augments currents elicited by the exogenous application
of subsaturating concentrations of GABA in voltage-clamped, cultured hippocampal
neurons and significantly prolongs the decay of autaptic IPSCs and miniature
IPSCs in our cultures. In addition, diethyl-lactam potentiates currents in
excised outside-out membrane patches elicited by the prolonged application of low
concentrations of GABA. However, when patches are exposed to 1-2 msec pulses of 1
mM GABA, diethyl-lactam does not alter current decay. Tiagabine, which blocks
GABA reuptake, does not prolong IPSCs, so it is unlikely that uptake inhibition
accounts for the enhancement of IPSCs. EPSCs and miniature IPSC frequency are
unaffected by diethyl-lactam, again consistent with a postsynaptic site of
action. We propose that during an IPSC, a substantial number of postsynaptic
receptors must be exposed to subsaturating concentrations of GABA. A simplified
model of GABAA receptor kinetics can account for the effects of diethyl-lactam on
exogenous GABA and IPSCs if diethyl-lactam has its main effect on the
monoliganded states of the GABAA receptor.
PMID- 9651195
TI - Neuroprotective actions of dipyridamole on cultured CNS neurons.
AB - We report that dipyridamole is neuroprotective for a variety of rat embryonic CNS
neurons cultured in serum-free basal medium lacking trophic factors or other
additives. We also describe the mechanism underlying this action. Neurons died
rapidly in basal medium but were rescued in large measure by 10 microM
dipyridamole. The protective action of dipyridamole seems to be attributable to
its antioxidant property. Vitamin E and N-acetylcysteine provided comparable
neuroprotection in basal medium, whereas an array of compounds that mimic other
actions of dipyridamole (inhibition of phosphodiesterases, blockade of nucleoside
and chloride transport, interference with the multidrug resistance protein, and
enhancement of prostacyclin synthesis) failed to promote survival. Thus, a major
cause of neuronal death in this system seems to be oxidative stress that is
relieved by dipyridamole. Iron plays a significant role in generation of such
stress, as indicated by the observations that addition of apotransferrin or iron
chelators to basal medium or use of iron-free medium also afforded protection.
Although oxidative stress was a major determinant of neuronal death, it was not
the only factor. Dipyridamole or other antioxidant measures did not provide
sustained neuroprotection. However, provision of insulin, which was not
protective alone in basal medium, along with dipyridamole significantly enhanced
long-term neuronal survival. Hence, optimal protection requires both trophic
support and relief from oxidative stress. These findings lend credence to the
potential use of dipyridamole or its derivatives in prevention and/or treatment
of CNS injuries and degenerative disorders in which oxidative stress is a
significant component.
PMID- 9651196
TI - Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal
kinases after neuronal injury.
AB - Transcription factor c-Jun is proposed to control neuronal cell death and
survival, but its activation by N-terminal phosphorylation and the underlying
activity of the c-Jun N-terminal kinases (JNKs) remain to be elucidated in the
adult mammalian brain. We generated a polyclonal antiserum that specifically
recognizes c-Jun phosphorylated at its serine 73 (S73) residue after UV
irradiation of 3T3 cells. Disruption of the c-jun locus in 3T3 cells abolished
this reaction, and retransfection of the human c-jun at the c-jun-/- background
restored it. The phospho-c-Jun antiserum was used to visualize N-terminally
phosphorylated c-Jun in the adult rat brain with cellular resolution. Prolonged c
Jun S73 phosphorylation was detected in affected neurons up to 5 d after
transient occlusion of medial cerebral artery or up to 50 d after transection of
central nerve fiber tracts. After cerebral ischemia-reperfusion, phosphorylation
of c-Jun was linked with induced expression of Fas-ligand (APO-1, CD95-ligand),
whose gene is a putative c-Jun/AP-1 target, and with terminal deoxynucleotidyl
transferase-mediated biotinylated UTP nick end labeling (TUNEL) reactivity, a
marker for apoptosis. After nerve fiber transection, however, lasting c-Jun
phosphorylation occurred in axotomized neurons negative for Fas-ligand or TUNEL
and regardless of degeneration or survival. In contrast to these lasting
phosphorylation patterns, transient seizure activity by pentylenetetrazole
provoked only a brief c-Jun phosphorylation and JNK activation. In extracts from
ischemic or axotomized brain compartments, c-Jun phosphorylation correlated with
enhanced long-term JNK activity, and in-gel kinase assays visualized proteins
with sizes corresponding to JNK isoforms as the only c-Jun N-terminally
phosphorylating enzymes. These results demonstrate that lasting c-Jun S73
phosphorylation and JNK activity are part of neuronal stress response after
neurodegenerative disorders in the adult mammalian brain with Fas-ligand as a
putative apoptotic effector.
PMID- 9651197
TI - Electrophysiological characterization of a putative supporting cell isolated from
the frog taste disk.
AB - Chemosensory cells in vertebrate taste organs have two obvious specializations:
an apical membrane with access to the tastants occurring in food, and synapses
with sensory axons. In many species, however, certain differentiated taste cells
have access to the tastants but lack any synaptic contacts with axons, and a
supportive rather than chemosensory function has been attributed to them. Until
now, no functional data are available for these taste cells. To begin to
understand their role in taste organ physiology, we have characterized with patch
clamp recording techniques the electrophysiological properties of a putative
supporting cell-the so-called wing cell-isolated from frog taste disks. Wing
cells were distinguished from chemosensory elements by the presence of a typical,
sheet-like apical process. Their resting potential was approximately -52 mV, and
the average input resistance was 4.8 GOmega. Wing cells possessed voltage-gated
Na+ currents sensitive to TTX, and an inactivating, voltage-gated K+ current
sensitive to TEA. Current injections elicited single action potentials but not
repetitive firing. We found no evidence for voltage-gated Ca2+ currents under
various experimental conditions. Amiloride-sensitive Na+ channels, thought to be
involved in Na+ chemotransduction, were present in wing cells. Many of the
membrane properties of wing cells have been also reported for chemosensory taste
cells. The presence of ion channels in wing cells might be suggestive of a role
in controlling the microenvironment inside the taste organs or the functioning of
chemosensory cells or both. In addition, they might participate directly in the
sensory transduction events by allowing loop currents to flow inside the taste
organs during chemostimulation.
PMID- 9651198
TI - Cyclosporin A, but not FK 506, protects mitochondria and neurons against
hypoglycemic damage and implicates the mitochondrial permeability transition in
cell death.
AB - Induction of the mitochondrial permeability transition (MPT) has been implicated
in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel
in the inner mitochondrial membrane, the mitochondrial megachannel, opens and
causes isolated mitochondria to swell. MPT and mitochondrial swelling is
inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells.
Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage
when administered 30 min before insulin-induced hypoglycemic isoelectricity of 30
min duration. Ultrastructural examination of the dentate gyrus revealed a marked
swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA
treated animals, mitochondria resumed a normal and contracted appearance during
and after the hypoglycemic insult. Treatment with FK 506 (2 mg/kg, i.v.), a
compound with immunosuppressive action similar to that of CsA, was not
protective. Studies on the swelling kinetics of isolated mitochondria from the
hippocampus showed that CsA, but not FK 506, inhibits calcium ion-induced MPT. We
conclude that CsA treatment during hypoglycemic coma inhibits the MPT and reduces
damage and that mitochondria and the MPT are likely to be involved in the
development of hypoglycemic brain damage in the rat.
PMID- 9651199
TI - Neuromodulators enhance transmitter release by two separate mechanisms at the
inhibitor of crayfish opener muscle.
AB - A presynaptic voltage control method has been used to investigate the modulatory
effects of serotonin (5-HT) and okadaic acid (OA) on the inhibitory junction of
the crayfish opener muscle. Instead of using action potentials, we used 20 msec
pulses depolarized to 0 mV to activate transmitter release. This approach allowed
us to monitor two separate physiological parameters related to the release
process. The first parameter, transmitter release kinetics, is characterized as
the delay when inhibitory postsynaptic conductance reaches its half-maximum
(IPSG50). The second parameter, the total area of IPSG (IPSGarea), estimates
total transmitter output. We have reported previously that the F2 component of
synaptic facilitation is associated with a decrease in IPSG50 but without a
change in IPSGarea. These results raised the possibility that IPSG50 and IPSGarea
could be mediated by separate mechanisms that were modulated independently. To
explore this possibility, we investigated the effects of 5-HT (100-200 nM) and OA
(2.5 microM) on the two parameters. 5-HT and OA enhanced IPSG neither by changing
the sensitivity of postsynaptic receptors, as tested by iontophoretically ejected
GABA, nor by elevating resting and action potential-activated presynaptic free
calcium, as monitored by fura-2 imaging. 5-HT and OA decreased IPSG50 by 3.0 +/-
1.4 and 3.6 +/- 1.1 msec, respectively, and increased IPSGarea by 50 +/- 21 and
37 +/- 6%, respectively. The ability of F2 facilitation to accelerate release
kinetics was reduced in the presence of the modulators, suggesting that the
mechanism underlying the accelerated release kinetics was shared by the two modes
of synaptic enhancement. This report demonstrates that the acceleration in
release kinetics and the increase in total release are two separate mechanisms
for enhancing transmitter output and that these two mechanisms can be activated
without changes in presynaptic calcium dynamics.
PMID- 9651200
TI - P2Y2 nucleotide receptors expressed heterologously in sympathetic neurons inhibit
both N-type Ca2+ and M-type K+ currents.
AB - The P2Y2 receptor is a uridine/adenosine triphosphate (UTP/ATP)-sensitive G
protein-linked nucleotide receptor that previously has been reported to stimulate
the phosphoinositide signaling pathway. Messenger RNA for this receptor has been
detected in brain tissue. We have investigated the coupling of the molecularly
defined rat P2Y2 receptor to neuronal N-type Ca2+ channels and to M-type K+
channels by heterologous expression in rat superior cervical sympathetic (SCG)
neurons. After the injection of P2Y2 cRNA, UTP inhibited the currents carried by
both types of ion channel. As previously reported [Filippov AK, Webb TE, Barnard
EA, Brown DA (1997) Inhibition by heterologously expressed P2Y2 nuerones. Br J
Pharmacol 121:849-851], UTP inhibited the Ca2+ current (ICa(N)) by up to 64%,
with an IC50 of approximately 0.5 microM. We now find that UTP also inhibited the
K+M current (IK(M)) by up to 61%, with an IC50 of approximately 1.5 microM. UTP
had no effect on either current in neurons not injected with P2Y2 cRNA. Structure
activity relations for the inhibition of ICa(N) and IK(M) in P2Y2 cRNA-injected
neurons were similar, with UTP >/= ATP > ITP >> GTP,UDP. However, coupling to
these two channels involved different G-proteins: pretreatment with Pertussis
toxin (PTX) did not affect UTP-induced inhibition of IK(M) but reduced inhibition
of ICa(N) by approximately 60% and abolished the voltage-dependent component of
this inhibition. In unclamped neurons, UTP greatly facilitated depolarization
induced action potential discharges. Thus, the single P2Y2 receptor can couple to
at least two G-proteins to inhibit both Ca2+N and K+M channels with near-equal
facility. This implies that the P2Y2 receptor may induce a broad range of
effector responses in the nervous system.
PMID- 9651201
TI - Dopamine D1-like receptor activation excites rat striatal large aspiny neurons in
vitro.
AB - The aim of this study was to elucidate electrophysiologically the actions of
dopamine and SKF38393, a D1-like dopamine receptor agonist, on the membrane
excitability of striatal large aspiny neurons (cholinergic interneurons). Whole
cell and perforated patch-clamp recordings were made of striatal cholinergic
neurons in rat brain slice preparations. Bath application of dopamine (1-100
microM) evoked a depolarization/inward current with an increase, a decrease, or
no change in membrane conductance in a dose-dependent manner. This effect was
antagonized by SCH23390, a D1-like dopamine receptor antagonist. The current
voltage relationships of the dopamine-induced current determined in 23 cells
suggested two conductances. In 10 cells the current reversed at -94 mV,
approximately equal to the K+ equilibrium potential (EK); in three cells the I-V
curves remained parallel, whereas in 10 cells the current reversed at -42 mV,
which suggested an involvement of a cation permeable channel. Change in external
K+ concentration shifted the reversal potential as expected for Ek in low Na+
solution. The current observed in 2 mM Ba2+-containing solution reversed at -28
mV. These actions of dopamine were mimicked by application of SKF38393 (1-50
microM) or forskolin (10 microM), an adenylyl cyclase activator, and were blocked
by SCH23390 (10 microM) or SQ22536 (300 microM), an inhibitor of adenylyl
cyclase. These data indicate, first, that dopamine depolarizes the striatal large
aspiny neurons by a D1-mediated suppression of resting K+ conductance and an
opening of a nonselective cation channel and, second, that both mechanisms are
mediated by an adenylyl cyclase-dependent pathway.
PMID- 9651202
TI - Alternative RNA splicing of the NMDA receptor NR1 mRNA in the neurons of the
teleost electrosensory system.
AB - The sequence for cDNA encoding the NMDA receptor subunit 1 (aptNR1) of the weakly
electric fish Apteronotus leptorhynchus has been determined. The deduced amino
acid sequence is approximately 88% identical to other vertebrate NR1 proteins,
with sequence homology extending to the alternatively spliced cassettes N1 and
C1. The fish and mammalian N1 and C1 splice cassettes are identical at 20 of 21
and 30 of 37 amino acid positions, respectively. We did not detect a C2 splice
cassette in aptNR1 mRNA, but we did find two novel C-terminal alternative splice
cassettes labeled C1' and C1". The relative levels of NR1 transcripts containing
the N1 and C1 splice cassettes were determined by using RNase protection and in
situ hybridization analysis. N1-containing mRNAs are more abundant in caudal
brain regions, similar to the patterns reported for mammalian brain. In contrast,
the relative levels of transcripts containing the C1 splice cassette are much
lower in fish than in mammals, averaging only 9% for the whole brain. The levels
of C1 splicing increased in more rostral brain regions. In situ hybridizations
with N1- and C1-specific probes demonstrated that N1 cassette splicing occurs in
most neurons but that C1 splicing is heterogeneous and is restricted to a subset
of neuronal types in the electrosensory system.
PMID- 9651203
TI - Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting
chondroitin sulfate proteoglycan.
AB - Chondroitin sulfate proteoglycans (CSPGs) are implicated in the regulation of
axonal growth. We previously reported that the neurite-promoting activity of
laminin is inhibited by association with a Schwann cell-derived CSPG and that
endoneurial laminin may be inhibited by this CSPG as well [Zuo J, Hernandez YJ,
Muir D (1998) Chondroitin sulfate proteoglycan with neurite-inhibiting activity
is upregulated after peripheral nerve injury. J Neurobiol 34:41-54]. Mechanisms
regulating axonal growth were studied by using an in vitro bioassay in which
regenerating embryonic dorsal root ganglionic neurons (DRGn) were grown on
sections of normal adult nerve. DRGn achieved slow neuritic growth on sections of
normal nerve, which was reduced significantly by treatment with metalloproteinase
inhibitors. Similar results were obtained on a synthetic substratum composed of
laminin and inhibitory CSPG. DRGn expressed the matrix metalloproteinase, MMP-2,
which was transported to the growth cone. Recombinant MMP-2 inactivated the
neurite-inhibiting CSPG without hindering the neurite-promoting potential of
laminin. Similarly, neuritic growth by DRGn cultured on normal nerve sections was
increased markedly by first treating the nerve sections with MMP-2. The
proteolytic deinhibition by MMP-2 was equivalent to and nonadditive with that
achieved by chondroitinase, suggesting that both enzymes inactivated inhibitory
CSPG. Additionally, the increases in neuritic growth resulting from treating
nerve sections with MMP-2 or chondroitinase were blocked by anti-laminin
antibodies. From these results we conclude that MMP-2 provides a mechanism for
the deinhibition of laminin in the endoneurial basal lamina and may play an
important role in the regeneration of peripheral nerve.
PMID- 9651204
TI - Response of thalamocortical neurons to hypoxia: a whole-cell patch-clamp study.
AB - The effect of hypoxia (3-4 min of 95% N2, 5% CO2) on thalamocortical (TC) neurons
was investigated using the whole-cell patch-clamp technique in rat dorsal lateral
geniculate nucleus slices kept submerged at 32 degreesC. The predominant feature
of the response of TC neurons to hypoxia was an increase in input conductance
(DeltaGN = 117 +/- 15%, n = 33) that was accompanied by an inward shift in
baseline holding current (IBH) at -65 and -57 mV (DeltaIBH = -45 +/- 6 pA, n =
18, and -25 +/- 8 pA, n = 33, respectively) but not at -40 mV. The hypoxia
induced increase in GN (as well as the shift in IBH) was abolished by procedures
that are known to block Ih, i.e., bath application of 4-(N-ethyl-N-phenylamino)
1, 2-dimethyl-6-(methylamino)-pyrimidinium chloride (100-300 microM) (DeltaGN = 5
+/- 13%, n = 11) and CsCl (2-3 mM) (DeltaGN = 16 +/- 16%, n = 5), or low [Na+]o
(DeltaGN = 10 +/- 10%, n = 5), whereas bath application of BaCl2 (0.1-2.0 mM) had
no significant effect (DeltaGN = 128 +/- 14%, n = 8). The hypoxic response was
also abolished in low [Ca+2]o (DeltaGN = 25 +/- 16%, DeltaIBH = -6 +/- 8 pA, n =
13), but was unaffected by recording with electrodes containing EGTA (10 mM),
BAPTA (10-30 mM), Cs+, or Cl-, as well as in the presence of external
tetraethylammonium and 4-aminopyridine. Furthermore, preincubation of the slices
with botulinum toxin A (100 nM), which is known to reduce Ca2+-dependent
transmitter release, blocked the hypoxic response (DeltaGN = -3 +/- 15%, DeltaIBH
= 10 +/- 5 pA, n = 4). We suggest that a positive shift in the voltage-dependence
of Ih and a change in its activation kinetics, which transforms it into a fast
activating current, may be responsible for the hypoxia-induced changes in GN and
IBH, probably via an increase in Ca+2-dependent transmitter release.
PMID- 9651205
TI - Preferential utilization of acetate by astrocytes is attributable to transport.
AB - Exogenous acetate is preferentially metabolized by astrocytes in the CNS, but the
biochemical basis for this selectivity is unknown. We observed that rat cortical
astrocytes produce 14CO2 from 0.2 mM [14C]acetate at a rate of 0.43 nmol/min per
milligram of protein, 18 times faster than cortical synaptosomes. Subsequent
studies examined whether this was attributable to cellular differences in the
transport or metabolism of acetate. The activity of acetyl-CoA synthetase, the
first enzymatic step in acetate utilization, was greater in synaptosomes than in
astrocytes (5.0 and 2.9 nmol/min per milligram of protein), indicating that
slower metabolism in synaptosomes cannot be attributed to lack of enzymatic
activity. [14C]Acetate uptake in astrocytes is rapid and time-dependent and
follows saturation kinetics (Vmax, 498 nmol/min per milligram of protein; Km, 9.3
mM). Uptake is inhibited stereospecifically by L-lactate as well as by pyruvate,
fluoroacetate, propionate, and alpha-cyano-4-hydroxycinnamate (CHC). Preloading
astrocytes with L-lactate or acetate, but not D-lactate, pyruvate, or glyoxylate,
transaccelerates [14C]acetate uptake. Acetate uptake by astrocytes appears to be
mediated by a carrier with properties similar to that of monocarboxylate
transport. In contrast, studies with synaptosomes provided no evidence for time
dependent, saturable, transaccelerated, or CHC-inhibitable uptake of
[14C]acetate. The high rate of transport in astrocytes compared with synaptosomes
explains the rapid incorporation of [14C]acetate into brain glutamine over
glutamate. These findings provide support for the use of acetate as a marker for
glial metabolism and suggest that extracellular acetate in the brain generated
from acetylcholine and ethanol metabolism is accumulated first by astrocytes.
PMID- 9651206
TI - The sodium channel Scn8a is the major contributor to the postnatal developmental
increase of sodium current density in spinal motoneurons.
AB - Sodium currents were recorded from motoneurons that were isolated from mice at
postnatal days 0-8 (P0-P8) and maintained in culture for 12-24 hr. Motoneurons
from normal mice exhibited a more than threefold increase in peak sodium current
density from P0 to P8. For mice lacking a functional Scn8a sodium channel gene,
motoneuronal sodium current density was comparable at P0 to that of normal mice
but failed to increase from P0 to P8. The absence of Scn8a sodium channels is
associated with the phenotype "motor end plate disease," which is characterized
by a progressive neuromuscular failure and is fatal by 3-4 postnatal weeks. Thus,
it appears that the development and function of mature motoneurons depends on the
postnatal induction of Scn8a expression.
PMID- 9651207
TI - G-Protein-dependent facilitation of neuronal alpha1A, alpha1B, and alpha1E Ca
channels.
AB - Modulation of neuronal voltage-gated Ca channels has important implications for
synaptic function. To investigate the mechanisms of Ca channel modulation, we
compared the G-protein-dependent facilitation of three neuronal Ca channels.
alpha1A, alpha1B, or alpha1E subunits were transiently coexpressed with alpha2
deltab and beta3 subunits in HEK293 cells, and whole-cell currents were recorded.
After intracellular dialysis with GTPgammaS, strongly depolarized conditioning
pulses facilitated currents mediated by each Ca channel type. The magnitude of
facilitation depended on current density, with low-density currents being most
strongly facilitated and high-density currents often lacking facilitation.
Facilitating depolarizations speeded channel activation approximately 1.7-fold
for alpha1A and alpha1B and increased current amplitudes by the same proportion,
demonstrating equivalent facilitation of G-protein-inhibited alpha1A and alpha1B
channels. Inactivation typically obscured facilitation of alpha1E current
amplitudes, but the activation kinetics of alpha1E currents showed consistent and
pronounced G-protein-dependent facilitation. The onset and decay of facilitation
had the same kinetics for alpha1A, alpha1B, and alpha1E, suggesting that Gbeta
gamma dimers dissociate from and reassociate with these Ca channels at very
similar rates. To investigate the structural basis for N-type Ca channel
modulation, we expressed a mutant of alpha1B missing large segments of the II-III
loop and C terminus. This deletion mutant exhibited undiminished G-protein
dependent facilitation, demonstrating that a Gbeta gamma interaction site
recently identified within the C terminus of alpha1E is not required for
modulation of alpha1B.
PMID- 9651208
TI - Membrane current induced by protein kinase C activators in rhabdomeric
photoreceptors: implications for visual excitation.
AB - Visual excitation in rhabdomeric photoreceptors is thought to be mediated by
activation of a light-regulated phospholipase C (PLC) and the consequent
hydrolysis of phosphatidylinositol bisphosphate. Whereas much attention has been
devoted to inositol trisphosphate (IP3) production and intracellular Ca2+
release, little is known about the possible role of the DAG branch in the
generation of the light response. We have tested the effect of chemically
distinct surrogates of DAG on isolated Lima photoreceptors. Application of the
phorbol ester PMA (0.5-10 microM) or the alkaloid (-)-indolactam (20-100 microM)
from a holding potential of -50 mV elicited an inward current, several hundred
picoamperes in amplitude, accompanied by a pronounced increase in membrane
conductance. The stereoisomers 4alpha-PMA and (+)-indolactam were both inactive,
arguing for the specificity of the effects. Elevation of cytosolic Ca2+ by
intracellular dialysis accelerated this current, whereas chelerythrine
antagonized it, suggesting the involvement of PKC. The reversal potential of the
membrane current induced by PKC activators was approximately +10 mV; replacement
of extracellular Na with impermeant N-methyl-D-glucamine decreased its amplitude
and shifted the reversal potential in the negative direction. Stimulation by PMA
and (-)-indolactam was accompanied by a pronounced depression of light
responsiveness; conversely, steady illumination reduced the size of the current
elicited by these PKC activators. Taken together, these results support the
notion that the DAG branch of the PLC cascade, in addition to its suggested
participation in visual adaptation, may play a role in the activation of the
photoresponse or a component thereof, probably in synergy with IP3-mediated Ca2+
release.
PMID- 9651209
TI - The activity of a highly promiscuous AP-1 element can be confined to neurons by a
tissue-selective repressive element.
AB - Tissue-specific gene transcription can be determined by the use of either
positive-acting or negative-acting DNA regulatory elements. We have analyzed a
promoter from the growth-associated protein 43 (GAP-43) gene and found that it
uses both of these mechanisms to achieve its high degree of neuron-specific
activity. Two novel transcription factor binding sites, designated Cx1 and Cx2,
drive promoter activity in neurons from developing cerebral cortex but not in
several other cell types. The promoter also contains an activator protein 1 (AP
1) site that contributes to activity in neurons. The AP-1 site can drive promoter
activity in a wide range of non-neuronal cells that express little or no
endogenous GAP-43, but only in the absence of a tissue-specific repressive
element located downstream of the GAP-43 TATA box. These findings suggest that
the GAP-43 repressive element plays an important role in allowing AP-1 signaling
pathways to modulate activity of the GAP-43 gene in neurons, without also causing
inappropriate activation by AP-1 transcription factors in other cell types.
PMID- 9651210
TI - Withdrawal from 3alpha-OH-5alpha-pregnan-20-One using a pseudopregnancy model
alters the kinetics of hippocampal GABAA-gated current and increases the GABAA
receptor alpha4 subunit in association with increased anxiety.
AB - In the present study, we have characterized properties of steroid withdrawal
using a pseudopregnant rat model. This paradigm results in increased production
of endogenous progesterone from ovarian sources and as such is a useful
physiological model. "Withdrawal" from progesterone induced by ovariectomy on day
12 of pseudopregnancy resulted in increased anxiety, as determined by a decrease
in open arm entries on the elevated plus maze compared to control rats and
pseudopregnant animals not undergoing withdrawal. Similar findings were obtained
24 hr after administration of a 5alpha-reductase blocker to a pseudopregnant
animal, suggesting that it is the GABAA-modulatory 3alpha-OH-5alpha-pregnan-20
one (3alpha, 5alpha-THP) that produces anxiogenic withdrawal symptoms. Twenty
four hours after steroid withdrawal, the time constant for decay of GABAA-gated
current was also reduced sixfold, assessed using whole- cell patch-clamp
procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. Thus,
3alpha,5alpha-THP withdrawal results in a marked decrease in total GABAA current,
a possible mechanism for its anxiogenic, proconvulsant sequelae. In addition,
3alpha,5alpha-THP withdrawal resulted in insensitivity to the normally
potentiating effect of the benzodiazepine lorazepam (LZM) on GABAA-gated Cl-
current. This withdrawal profile is similar to that reported for other GABAA
modulatory drugs such as the benzodiazepines (BDZs), barbiturates, and ethanol.
These changes were also associated with significant two and threefold increases
in both the mRNA and protein for the alpha4 subunit of the GABAA receptor,
respectively, in hippocampus. The pseudopregnancy paradigm may be a useful model
for periods of endogenous 3alpha,5alpha-THP withdrawal such as premenstrual
syndrome and postpartum or postmenopausal dysphoria, when increased emotional
lability and BDZ insensitivity have been reported.
PMID- 9651211
TI - Vasoactive intestinal peptide enhances its own expression in sympathetic neurons
after injury.
AB - Neurons in the adult rat superior cervical sympathetic ganglion (SCG)
dramatically increase their content of vasoactive intestinal peptide (VIP) and
its mRNA after axotomy in vivo and after explantation. Because the VIP gene
contains a functional cAMP response element, the effects of cAMP-elevating agents
on VIP expression were examined. VIP, forskolin, or isoproterenol increased cAMP
accumulation in explanted ganglia. Secretin, a peptide chemically related to VIP,
or forskolin increased VIP levels above those seen in ganglia cultured in control
medium, whereas treatment with VIP or secretin increased the level of peptide
histidine isoleucine (PHI), a peptide coded for by the same mRNA that encodes
VIP. VIP or forskolin also increased VIP-PHI mRNA. In contrast, isoproterenol did
not alter levels of VIP, PHI, or VIP-PHI mRNA. Although VIP or forskolin
increased cAMP levels in both dissociated neurons and in non-neuronal cells,
isoproterenol significantly stimulated cAMP accumulation only in the latter. VIP6
28 was an effective antagonist of the actions of exogenous VIP on cAMP and VIP
PHI mRNA in neuron-enriched cultures. When adult SCG explants were cultured in
defined medium, endogenous VIP immunoreactivity was released. When VIP6-28 was
added to such cultures, it significantly inhibited the increase in VIP-PHI mRNA
that normally occurs. These data indicate that VIP, or a closely related
molecule, produced by adult neurons after injury can enhance the expression of
VIP. Such a mechanism may prolong the period during which VIP is elevated after
axonal damage. The possibility is also discussed that, because VIP is present in
preganglionic neurons in normal animals, its release during periods of increased
sympathetic nerve activity could alter VIP expression in the SCG.
PMID- 9651212
TI - Comparison of hippocampal dendritic spines in culture and in brain.
AB - We have quantified hippocampal spine structure at the light and ultrastructural
levels in cell cultures approximately 1- 3 weeks old and in the brains of rodents
5 and 21 d old. The number of spines bearing synapses increases with age in
cultures and in brain, but the structures are similar in both. In culture, about
half of the synapses are formed on spines and the remainder are formed on
dendritic shafts. In the 5-d-old brain, about half of the synapses occur on
dendritic shafts, by 3 weeks of age only approximately 20% of synapses are found
on dendritic shafts, and in the adult shaft synapses are very rare.
PMID- 9651213
TI - A complex program of striatal gene expression induced by dopaminergic
stimulation.
AB - Dopamine acting in the striatum is necessary for normal movement and motivation.
Drugs that change striatal dopamine neurotransmission can have long-term effects
on striatal physiology and behavior; these effects are thought to involve
alterations in gene expression. Using the 6-hydroxydopamine lesion model of
Parkinson's disease and differential display PCR, we have identified a set of
more than 30 genes whose expression rapidly increases in response to stimulation
of striatal dopamine D1 receptors. The induced mRNAs include both novel and
previously described genes, with diverse time courses of expression. Some genes
are expressed at near-maximal levels within 30 min, whereas others show no
substantial induction until 2 hr or more after stimulation. Some of the induced
genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a
homeostatic response to excessive stimulation. Others may be part of a genetic
program involved in cellular and synaptic plasticity. A very similar set of genes
is induced in unlesioned animals by administration of the psychostimulant cocaine
or the antipsychotic eticlopride, although in distinct striatal cell populations.
In contrast to some previously described early genes, most of the novel genes are
not induced in cortex by apomorphine, indicating specificity of induction. Thus
we have identified novel components of a complex, coordinated genetic program
that is induced in striatal cells in response to various dopaminergic
manipulations.
PMID- 9651215
TI - Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol.
AB - Marijuana consumption elicits diverse physiological and psychological effects in
humans, including memory loss. Here we report that Delta9-tetrahydrocannabinol
(THC), the major psychoactive component of marijuana, is toxic for hippocampal
neurons. Treatment of cultured neurons or hippocampal slices with THC caused
shrinkage of neuronal cell bodies and nuclei as well as genomic DNA strand
breaks, hallmarks of neuronal apoptosis. Neuron death induced by THC was
inhibited by nonsteroidal anti-inflammatory drugs, including indomethacin and
aspirin, as well as vitamin E and other antioxidants. Furthermore, treatment of
neurons with THC stimulated a significant increase in the release of arachidonic
acid. We hypothesize that THC neurotoxicity is attributable to activation of the
prostanoid synthesis pathway and generation of free radicals by cyclooxygenase.
These data suggest that some of the memory deficits caused by cannabinoids may be
caused by THC neurotoxicity.
PMID- 9651214
TI - The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is
endocytosed via the clathrin-mediated pathway.
AB - Cell-cell interactions mediated via cell adhesion molecules (CAMs) are
dynamically regulated during nervous system development. One mechanism to control
the amount of cell surface CAMs is to regulate their recycling from the plasma
membrane. The L1 subfamily of CAMs has a highly conserved cytoplasmic domain that
contains a tyrosine, followed by the alternatively spliced RSLE (Arg-Ser-Leu-Glu)
sequence. The resulting sequence of YRSL conforms to a tyrosine-based sorting
signal that mediates clathrin-dependent endocytosis of signal-bearing proteins.
The present study shows that L1 associates in rat brain with AP-2, a clathrin
adaptor that captures plasma membrane proteins with tyrosine-based signals for
endocytosis by coated pits. In vitro assays demonstrate that this interaction
occurs via the YRSL sequence of L1 and the mu 2 chain of AP-2. In L1-transfected
3T3 cells, L1 endocytosis is blocked by dominant-negative dynamin that
specifically disrupts clathrin-mediated internalization. Furthermore, endocytosed
L1 colocalizes with the transferrin receptor (TfR), a marker for clathrin
mediated internalization. Mutant forms of L1 that lack the YRSL do not colocalize
with TfR, indicating that the YRSL mediates endocytosis of L1. In neurons, L1 is
endocytosed preferentially at the rear of axonal growth cones, colocalizing with
Eps15, another marker for the clathrin endocytic pathway. These results establish
a mechanism by which L1 can be internalized from the cell surface and suggest
that an active region of L1 endocytosis at the rear of growth cones is important
in L1-dependent axon growth.
PMID- 9651216
TI - Regulated expression of the cell adhesion glycoprotein F3 in adult hypothalamic
magnocellular neurons.
AB - F3, a glycoprotein of the immunoglobulin superfamily implicated in axonal growth,
occurs in oxytocin (OT)-secreting and vasopressin (AVP)-secreting neurons of the
adult hypothalamo-neurohypophysial system (HNS) whose axons undergo morphological
changes in response to stimulation. Immunocytochemistry and immunoblot analysis
showed that during basal conditions of HNS secretion, there are higher levels of
this glycosylphosphatidyl inositol-anchored protein in the neurohypophysis, where
their axons terminate, than in the hypothalamic nuclei containing their somata.
Physiological stimulation (lactation, osmotic challenge) reversed this pattern
and resulted in upregulation of F3 expression, paralleling that of OT and AVP
under these conditions. In situ hybridization revealed that F3 expression in the
hypothalamus is restricted to its magnocellular neurons and demonstrated a more
than threefold increase in F3 mRNA levels in response to stimulation. Confocal
and electron microscopy localized F3 in secretory granules in all neuronal
compartments, a localization confirmed by detection of F3 immunoreactivity in
granule-enriched fractions obtained by sucrose density gradient fractionation of
rat neurohypophyses. F3 was not visible on any cell surface in the magnocellular
nuclei. In contrast, in the neurohypophysis, it was present not only in secretory
granules but also on the surface of axon terminals and glia and in extracellular
spaces. Taken together, our observations reveal that the cell adhesion
glycoprotein F3 is colocalized with neurohypophysial peptides in secretory
granules. It follows, therefore, the regulated pathway of secretion in HNS
neurons to be released by exocytosis at their axon terminals in the
neurohypophysis, where it may intervene in activity-dependent structural axonal
plasticity.
PMID- 9651217
TI - Identification of the dopamine D3 receptor in oligodendrocyte precursors:
potential role in regulating differentiation and myelin formation.
AB - Expression of the dopamine D3 receptor (D3r) was found in primary mixed glial
cultures from newborn brain and in the corpus callosum in vivo during the peak of
myelination. Expression of the D3r mRNA, but not D2r mRNA, was detected as early
as 5 d in vitro (DIV) by RT-PCR. Immunoblot studies revealed D3r protein was also
expressed in the cultures. Double immunofluorescence analysis for the D3r and for
surface markers of specific stages of oligodendrocyte development indicated that
D3r expression occurred in precursors and in immature oligodendrocytes but not in
mature oligodendrocytes (i.e. , A2B5(+) 007(-) 01(-) and A2B5(+) 007(+) 01(-)
cells but not A2B5(-) 007(+) 01(+) cells). Confocal microscopic analysis
indicated that D3r was associated with cell bodies and cell membranes but not
with the processes emanating from cell somas. Immunohistochemistry of brain
sections revealed the presence of D3r in some oligodendrocytes located mainly
within the genu and radiato of the corpus callosum during the active period of
myelination. Treatment of cultures with 20 microM quinpirole led to decreased
numbers of O1(+) oligodendrocytes possessing myelin-like membranes as well as an
increase in the number of precursors in 14 DIV cultures. This effect was
prevented by the dopamine antagonist haloperidol. These results show that the D3r
expression is not restricted to neurons but it is also expressed in
differentiating oligodendrocytes before terminal maturation. It also suggests
that dopamine or some other D3r ligand may play a role in oligodendrocyte
differentiation and/or the formation of myelin by mature oligodendrocytes.
PMID- 9651218
TI - Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte
proliferation and myelination of regenerating axons in the contused adult rat
spinal cord.
AB - Functional loss after spinal cord injury (SCI) is caused, in part, by
demyelination of axons surviving the trauma. Neurotrophins have been shown to
induce oligodendrogliagenesis in vitro, but stimulation of oligodendrocyte
proliferation and myelination by these factors in vivo has not been examined. We
sought to determine whether neurotrophins can induce the formation of new
oligodendrocytes and myelination of regenerating axons after SCI in adult rats.
In this study, fibroblasts producing neurotrophin-3 (NT-3), brain-derived
neurotrophic factor (BDNF), ciliary neurotrophic factor, nerve growth factor,
basic fibroblast growth factor, or beta-galactosidase (control grafts) were
transplanted subacutely into the contused adult rat spinal cord. At 10 weeks
after injury, all transplants contained axons. NT-3 and BDNF grafts, however,
contained significantly more axons than control or other growth factor-producing
grafts. In addition, significantly more myelin basic protein-positive profiles
were detected in NT-3 and BDNF transplants, suggesting enhanced myelination of
ingrowing axons within these neurotrophin-producing grafts. To determine whether
augmented myelinogenesis was associated with increased proliferation of
oligodendrocyte lineage cells, bromodeoxyuridine (BrdU) was used to label
dividing cells. NT-3 and BDNF grafts contained significantly more BrdU-positive
oligodendrocytes than controls. The association of these new oligodendrocytes
with ingrowing myelinated axons suggests that NT-3- and BDNF-induced
myelinogenesis resulted, at least in part, from expansion of oligodendrocyte
lineage cells, most likely the endogenous oligodendrocyte progenitors. These
findings may have significant implications for chronic demyelinating diseases or
CNS injuries.
PMID- 9651219
TI - Type 1 inositol 1,4,5-trisphosphate receptor is required for induction of long
term depression in cerebellar Purkinje neurons.
AB - The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca2+
channel that releases Ca2+ from internal Ca2+ stores in response to InsP3.
Although InsP3R is highly expressed in various regions of the mammalian brain,
the functional role of this receptor has not been clarified. We show here that
cerebellar slices prepared from mice with a disrupted InsP3R type 1 gene, which
is predominantly expressed in Purkinje cells, completely lack long-term
depression (LTD), a model of synaptic plasticity in the cerebellum. Moreover, a
specific antibody against InsP3R1, introduced into wild-type Purkinje cells
through patch pipettes, blocked the induction of LTD. These data indicate that,
in addition to Ca2+ influx through Ca2+ channels on the plasma membrane, Ca2+
release from InsP3R plays an essential role in the induction of LTD, suggesting a
physiological importance for InsP3R in Purkinje cells.
PMID- 9651220
TI - Patterns of intracellular calcium fluctuation in precursor cells of the
neocortical ventricular zone.
AB - Changes in intracellular free calcium concentration ([Ca2+]i) are known to
influence a variety of events in developing neurons. Although spontaneous changes
of [Ca2+]i have been examined in immature cortical neurons, the calcium dynamics
of cortical precursor cells have received less attention. Using an intact
cortical mantle and confocal laser microscopy, we examined the spatiotemporal
patterns of spontaneous [Ca2+]i fluctuations in neocortical ventricular zone (VZ)
cells in situ. The majority of activity consisted of single cells that displayed
independent [Ca2+]i fluctuations. These events occurred in cells throughout the
depth of the VZ. Immunohistochemical staining confirmed that these events
occurred primarily in precursor cells rather than in postmitotic neurons. When
imaging near the ventricular surface, synchronous spontaneous [Ca2+]i increases
were frequently observed in pairs of adjacent cells. Cellular morphology, time
lapse imaging, and nuclear staining demonstrated that this activity occurred in
mitotically active cells. A third and infrequently encountered pattern of
activity consisted of coordinated spontaneous increases in [Ca2+]i in groups of
neighboring VZ cells. The morphological characteristics of these cells and
immunohistochemical staining suggested that the coordinated events occurred in
gap junction-coupled precursor cells. All three patterns of activity were
dependent on the release of Ca2+ from intracellular stores. These results
demonstrate distinct patterns of spontaneous [Ca2+]i change in cortical precursor
cells and raise the possibility that these dynamics may contribute to the
regulation of neurogenesis.
PMID- 9651221
TI - Tlx-1 and Tlx-3 homeobox gene expression in cranial sensory ganglia and hindbrain
of the chick embryo: markers of patterned connectivity.
AB - Recent evidence suggests that in vertebrates the formation of distinct neuronal
cell types is controlled by specific families of homeodomain transcription
factors. Furthermore, the expression domains of a number of these genes
correlates with functionally integrated neuronal populations. We have isolated
two members of the divergent T-cell leukemia translocation (HOX11/Tlx) homeobox
gene family from chick, Tlx-1 and Tlx-3, and show that they are expressed in
differentiating neurons of both the peripheral and central nervous systems. In
the peripheral nervous system, Tlx-1 and Tlx-3 are expressed in overlapping
domains within the placodally derived components of a number of cranial sensory
ganglia. Tlx-3, unlike Tlx-1, is also expressed in neural crest-derived dorsal
root and sympathetic ganglia. In the CNS, both genes are expressed in
longitudinal columns of neurons at specific dorsoventral levels of the hindbrain.
Each column has distinct anterior and/or posterior limits that respect inter
rhombomeric boundaries. Tlx-3 is also expressed in D2 and D3 neurons of the
spinal cord. Tlx-1 and Tlx-3 expression patterns within the peripheral and
central nervous systems suggest that Tlx proteins may be involved not only in the
differentiation and/or survival of specific neuronal populations but also in the
establishment of neuronal circuitry. Furthermore, by analogy with the LIM genes,
Tlx family members potentially define sensory columns early within the developing
hindbrain in a combinatorial manner.
PMID- 9651222
TI - Localized sources of neurotrophins initiate axon collateral sprouting.
AB - The sprouting of axon collateral branches is important in the establishment and
refinement of neuronal connections during both development and regeneration.
Collateral branches are initiated by the appearance of localized filopodial
activity along quiescent axonal shafts. We report here that sensory neuron axonal
shafts rapidly sprout filopodia at sites of contact with nerve growth factor
coated polystyrene beads. Some sprouts can extend up to at least 60 micro(m)
through multiple bead contacts. Axonal filopodial sprouts often contained
microtubules and exhibited a debundling of axonal microtubules at the site of
bead-axon contact. Cytochalasin treatment abolished the filopodial sprouting, but
not the accumulation of actin filaments at sites of bead-axon contact. The axonal
sprouting response is mediated by the trkA receptor and likely acts through a
phosphoinositide-3 kinase-dependent pathway, in a manner independent of
intracellular Ca2+ fluctuations. These findings implicate neurotrophins as local
cues that directly stimulate the formation of collateral axon branches.
PMID- 9651223
TI - Blocking N-cadherin function disrupts the epithelial structure of differentiating
neural tissue in the embryonic chicken brain.
AB - The cell adhesion molecule N-cadherin is ubiquitously expressed in the early
neuroepithelium, with strongest expression in the ependymal lining. We blocked
the function of N-cadherin during early chicken brain development by injecting
antibodies against N-cadherin into the tectal ventricle of embryos at 4-5 d of
incubation [embryonic day 4 (E4)-E5]. N-cadherin blockage results in massive
morphological changes in restricted brain regions. At approximately E6, these
changes consist of invaginations of pieces of the ependymal lining and the
formation of neuroepithelial rosettes. The rosettes are composed of central
fragments of ependymal lining, surrounded by an inner ventricular layer and an
outer mantle layer. Radial glia processes are radially arranged around the
ependymal centers of the rosettes. The normal layering of the neural tissue is
thus preserved, but its coherent epithelial structure is disrupted. The observed
morphological changes are restricted to specific brain regions such as the tectum
and the dorsal thalamus, whereas the ventral thalamus and the pretectum are
almost undisturbed. At E10-E11, analysis of late effects of N-cadherin blockage
reveals that in the dorsal thalamus, gray matter is fragmented and disorganized;
in the tectum, additional layers have formed at the ventricular surface.
Together, these results indicate that N-cadherin function is required for the
maintenance of a coherent sheet of neuroepithelium in specific brain regions.
Disruption of this sheet results in an abnormal morphogenesis of brain gray
matter.
PMID- 9651224
TI - Role of the nucleus raphe magnus in antinociception produced by ABT-594:
immediate early gene responses possibly linked to neuronal nicotinic
acetylcholine receptors on serotonergic neurons.
AB - Recently, a novel cholinergic channel modulator, (R)-5-(2-azetidinylmethoxy)-2
chloropyridine (ABT-594), was shown to produce potent analgesia in a variety of
rodent pain models when administered either systemically or centrally into the
nucleus raphe magnus (NRM). The purpose of the present study was to investigate
the possible supraspinal contribution of ABT-594 by assessing its ability to
induce expression of the immediate early gene c-fos, a biochemical marker of
neuronal activation, in the NRM of rats. Putative serotonergic neurons in the
NRM, a medullary nucleus proposed to be involved in descending antinociceptive
pathways, were identified immunohistochemically using a monoclonal antibody (mAb)
against tryptophan hydroxylase. ABT-594 (0.03-0.3 micromol/kg, i.p.) produced a
dose-dependent induction of Fos protein that was blocked by the central nicotinic
acetylcholine receptor (nAChR) antagonist mecamylamine (5 micromol/kg, i.p.) but
not by the peripheral nAChR antagonist hexamethonium (15 micromol/kg, i.p.).
Immunohistological studies using mAb 299 revealed the expression of alpha4
containing nAChRs in the NRM. The alpha4 immunostaining was dramatically reduced
by pretreating (30 d) animals with the serotonin neurotoxin 5,7
dihydroxytryptamine (5,7-DHT), which was previously shown to substantially
attenuate the antinociceptive actions of ABT-594. In a double immunohistochemical
labeling experiment, coexpression of the serotonin marker tryptophan hxdroxylase
and the alpha4 nAChR subunit in NRM neurons was observed. These results suggest
that the analgesic mechanism of ABT-594 may in part involve the activation of the
NRM, a site where alpha4-containing nAChRs are expressed by serotonergic neurons.
PMID- 9651225
TI - Monocular core zones and binocular border strips in primate striate cortex
revealed by the contrasting effects of enucleation, eyelid suture, and retinal
laser lesions on cytochrome oxidase activity.
AB - In primate striate cortex, geniculocortical afferents in layer IVc terminate in
parallel stripes called ocular dominance columns. We propose that this
segregation of ocular inputs generates a related but distinct columnar system of
monocular core zones alternating with binocular border strips. Evidence for this
functional parcellation was obtained by comparing the effects of enucleation,
eyelid suture, and retinal laser lesions on cytochrome oxidase (CO) activity in
eight macaques. Enucleation produced a high-contrast pattern of dark and light
columns in layer IVc, corresponding precisely to the ocular dominance columns,
whereas eyelid suture produced a low-contrast pattern of thin dark columns
alternating with wide pale columns. [3H]Proline eye injection showed that the
thin dark columns corresponded to the core zones of the open eye's ocular
dominance columns. The wide pale columns resulted from loss of CO activity in the
sutured eye's core zones and within both eyes' border strips. Loss of CO activity
within both eyes' border strips suggested that these regions are binocular. To
confirm our findings, we compared different CO patterns in the same cortex by
making retinal laser lesions in four animals. They produced a CO pattern
tantamount to "focal" enucleation, although contrast was low when laser damage
was confined to the outer retina. CO levels in cortical scotomas remained
severely depressed for months after retinal lesions, even when the other eye was
enucleated. This observation provided little anatomical support for the notion of
topographic plasticity after visual deafferentation. In a single human subject
with macular degeneration, CO revealed a low-contrast pattern of ocular dominance
columns, resembling the pattern in monkeys with laser-induced photoreceptor
damage.
PMID- 9651226
TI - Leukemia inhibitory factor is an anti-inflammatory and analgesic cytokine.
AB - The mRNA for leukemia inhibitory factor (LIF), a neuroimmune signaling molecule,
is elevated during skin inflammation produced by intraplantar injection of
complete Freund's adjuvant (CFA). Moreover, although LIF knock-out mice display
normal sensitivity to cutaneous mechanical and thermal stimulation compared with
wild-type mice, the degree of CFA-induced inflammation in mice lacking LIF is
enhanced in spatial extent, amplitude, cellular infiltrate, and interleukin (IL)
1beta and nerve growth factor (NGF) expression. Conversely, local injection of
low doses of recombinant LIF diminishes mechanical and thermal hypersensitivity
as well as the IL-1beta and NGF expression induced by CFA. These data show that
upregulation of LIF during peripheral inflammation serves a key, early anti
inflammatory role and that exogenous LIF can reduce inflammatory hyperalgesia.
PMID- 9651227
TI - Anterograde signaling by nitric oxide: characterization and in vitro
reconstitution of an identified nitrergic synapse.
AB - Nitric oxide (NO) is recognized as a signaling molecule in the CNS where it is a
candidate retrograde neurotransmitter. Here we provide direct evidence that NO
mediates slow excitatory anterograde transmission between the NO synthase (NOS)
expressing B2 neuron and an NO-responsive follower neuron named B7nor. Both are
motoneurons located in the buccal ganglia of the snail Lymnaea stagnalis where
they participate in feeding behavior. Transmission between B2 and B7nor is
blocked by inhibiting NOS and is suppressed by extracellular scavenging of NO.
Furthermore, focal application of NO to the cell body of the B7nor neuron causes
a depolarization that mimics the effect of B2 activity. The slow interaction
between the B2 and B7nor neurons can be re-established when the two neurons are
cocultured, and it shows the same susceptibility to NOS inhibition and NO
scavenging. In cell culture we have also examined spatial aspects of NO
signaling. We show that before the formation of an anatomical connection, the
presynaptic neuron can cause depolarizing potentials in the follower neuron at
distances up to 50 micro(m). The strength of the interaction increases when the
distance between the cells is reduced. Our results suggest that NO can function
as both a synaptic and a nonsynaptic signaling molecule.
PMID- 9651228
TI - Hypothalamic neurons preferentially respond to female nest coo stimulation:
demonstration of direct acoustic stimulation of luteinizing hormone release.
AB - Avian vocalizations are generally understood to play a pivotal role in
reproductive functions. The role of the hypothalamus in gonadotropin release in
higher vertebrates including birds is well established. To date, however, a
direct linkage between the neuronal processing of vocal input and the contingent
luteinizing hormone (LH) response has not been demonstrated. In this study, using
female ring doves, we recorded neuronal activity from hypothalamic nuclei that,
as we have shown previously, receive acoustic inputs from the auditory thalamic
relay. Concurrently with recording single-unit responses to stimulation with
species-specific coo vocalizations, we sampled LH levels in blood from the
pituitary veins. LH concentration in the plasma was significantly elevated in
birds hearing species-typical coos but not in birds exposed to experimentally
altered coos or white noise or in birds that received no vocal stimulation. We
found two types of neurons in the preoptic and anterior hypothalamus that
selectively responded to the female nest coo: excitatory units and inhibitory
units. Among the excitatory neurons are units characterized by two bursts
separated by a period of slow spiking or complete silence, in a pattern
approximately corresponding temporally to the two-note coo. We designate them as
female-nest-coo-specific units. Most neurons in the posterior hypothalamus were
nonselective in their response. Female nest coo and male nest coo stimulation
evoked an equal magnitude of discharge changes from responsive units in the
preoptic-anterior hypothalamic area. We found, however, that the LH increment was
three times greater for birds hearing female nest coos than for birds hearing
male nest coos. These observations suggest that feature-detecting neurons such as
the female-nest-coo-specific units are involved in gonadotropin-releasing hormone
output. The present findings are consistent with the well established behavioral
evidence that female nest coos mediate ovarian growth.
PMID- 9651229
TI - Behavioral state control through differential serotonergic inhibition in the
mesopontine cholinergic nuclei: a simultaneous unit recording and microdialysis
study.
AB - Cholinergic neurons of the mesopontine nuclei are strongly implicated in
behavioral state regulation. One population of neurons in the cholinergic zone of
the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as rapid
eye movement (REM)-on neurons, shows preferential discharge activity during REM
sleep, and extensive data indicate a key role in production of this state.
Another neuronal group present in the same cholinergic zone of the laterodorsal
tegmentum and the pedunculopontine nuclei, referred to as Wake/REM-on neurons,
shows preferential discharge activity during both wakefulness and REM sleep and
is implicated in the production of electroencephalographic activation in both of
these states. To test the hypothesis of differential serotonergic inhibition as
an explanation of the different state-related discharge activity, we developed a
novel methodology that enabled, in freely behaving animals, simultaneous unit
recording and local perfusion of neuropharmacological agents using a
microdialysis probe adjacent to the recording electrodes. Discharge activity of
REM-on neurons was almost completely suppressed by local microdialysis perfusion
of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH
DPAT), although this agonist had minimal or no effect on the Wake/REM-on neurons.
We conclude that selective serotonergic inhibition is a basis of differential
state regulation in the mesopontine cholinergic nuclei, and that the novel
methodology combining neurophysiological and neuropharmacological information
from the freely behaving animal shows great promise for further insight into the
neural basis of behavioral control.
PMID- 9651230
TI - Intracellular correlates of acquisition and long-term memory of classical
conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule
HVI.
AB - Intradendritic recordings in Purkinje cells from a defined area in parasaggital
slices of cerebellar lobule HVI, obtained after rabbits were given either paired
(classical conditioning) or explicitly unpaired (control) presentations of tone
and periorbital electrical stimulation, were used to assess the nature and
duration of conditioning-specific changes in Purkinje cell dendritic membrane
excitability. We found a strong relationship between the level of conditioning
and Purkinje cell dendritic membrane excitability after initial acquisition of
the conditioned response. Moreover, conditioning-specific increases in Purkinje
cell excitability were still present 1 month after classical conditioning.
Although dendritically recorded membrane potential, input resistance, and
amplitude of somatic and dendritic spikes were not different in cells from paired
or control animals, the size of a potassium channel-mediated transient
hyperpolarization was significantly smaller in cells from animals that received
classical conditioning. In slices of lobule HVI obtained from naive rabbits, the
conditioning-related increases in membrane excitability could be mimicked by
application of potassium channel antagonist tetraethylammonium chloride,
iberiotoxin, or 4-aminopyridine. However, only 4-aminopyridine was able to reduce
the transient hyperpolarization. The pharmacological data suggest a role for
potassium channels and, possibly, channels mediating an IA-like current, in
learning-specific changes in membrane excitability. The conditioning-specific
increase in Purkinje cell dendritic excitability produces an
afterhyperpolarization, which is hypothesized to release the cerebellar deep
nuclei from inhibition, allowing conditioned responses to be elicited via the red
nucleus and accessory abducens motorneurons.
PMID- 9651231
TI - Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired
pulse facilitation.
AB - Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder
characterized by ataxia, progressive motor deterioration, and loss of cerebellar
Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the
function of the SCA1 gene product ataxin-1, a novel protein without homology to
previously described proteins, we generated mice with a targeted deletion in the
murine Sca1 gene. Mice lacking ataxin-1 are viable, fertile, and do not show any
evidence of ataxia or neurodegeneration. However, Sca1 null mice demonstrate
decreased exploratory behavior, pronounced deficits in the spatial version of the
Morris water maze test, and impaired performance on the rotating rod apparatus.
Furthermore, neurophysiological studies performed in area CA1 of the hippocampus
reveal decreased paired-pulse facilitation in Sca1 null mice, whereas long-term
and post-tetanic potentiations are normal. These findings demonstrate that SCA1
is not caused by loss of function of ataxin-1 and point to the possible role of
ataxin-1 in learning and memory.
PMID- 9651232
TI - Glutamate receptor targeting to synaptic populations on Purkinje cells is
developmentally regulated.
AB - Selective targeting of neurotransmitter receptors to specific synapse populations
occurs in adult neurons, but little is known about the development of these
receptor distribution patterns. In this study, we demonstrate that a specific
developmental switch occurs in the targeting of a receptor to an identified
synapse population. Localization of delta and AMPA glutamate receptors at
parallel and climbing fiber synapses on the developing Purkinje cells was studied
using postembedding immunogold. Delta receptors were found to be abundant on
postsynaptic membranes at parallel fiber synapses from postnatal day 10 (P10) to
adult. In contrast, delta receptors were found to be high at climbing fiber
synapses only at P10 and P14. Thus, a major finding of this paper is that high
levels of delta receptors are transiently expressed in climbing fiber synapses in
the second postnatal week. Labeling of synapses with anti-delta receptor antibody
at P10 was limited to the postsynaptic membrane of excitatory synapses and was
absent from GABAergic synapses. Unlike delta receptor immunolabeling, AMPA
receptor immunolabeling (GluR2/3 and GluR2 antibodies) was high in the
postsynaptic membranes of synapses at early postnatal ages (P2 and P5) and was
higher in climbing fiber synapses than in parallel fiber synapses from P10 to
adult. The present study shows that synapse-specific targeting of glutamate
receptors in Purkinje cells is developmentally regulated, with the postsynaptic
receptor composition established during synapse maturation. This composition is
not dependent on the nature of the initial establishment of synaptic connections.
PMID- 9651233
TI - The role of corticotropin-releasing factor and corticosterone in stress- and
cocaine-induced relapse to cocaine seeking in rats.
AB - We have shown previously that footshock stress and priming injections of cocaine
reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al.,
1996). Here we examined the role of brain corticotropin-releasing factor (CRF)
and the adrenal hormone corticosterone in stress- and cocaine-induced
reinstatement of cocaine seeking in rats. The ability of footshock stress and
priming injections of cocaine to induce relapse to cocaine seeking was studied
after intracerebroventricular infusions of the CRF receptor antagonist D-Phe
CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone
replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion,
i.v) for 3 hr daily for 10-14 d and were then placed on an extinction schedule
during which saline was substituted for cocaine. Tests for reinstatement were
given after intermittent footshock (10 min; 0.5 mA) and after priming injections
of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in
both intact animals and animals with corticosterone replacement but not in
adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked
footshock-induced reinstatement at all doses tested in both intact animals and
animals with corticosterone replacement. Reinstatement by priming injections of
cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D
Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress
induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine
seeking. Furthermore, the data show that although reinstatement of cocaine
seeking by footshock stress requires minimal, basal, levels of corticosterone,
stress-induced increases in corticosterone do not play a role in this effect.
PMID- 9651234
TI - Absence of fenfluramine-induced anorexia and reduced c-Fos induction in the
hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out
mice.
AB - Fenfluramine, a serotonin releaser and uptake inhibitor, has been widely
prescribed as an appetite suppressant. Despite its popular clinical use, however,
the precise neural pathways and specific 5-HT receptors that account for its
anorectic effect have yet to be elucidated. To test the hypothesis that
stimulation of 5-HT1B receptors is required for the anorectic effect of
fenfluramine, we assessed food intake in wild-type and 5-HT1B knock-out mice.
Next, to determine possible brain structures and pathways that may contribute to
the 5-HT1B-mediated effects of fenfluramine, we studied by immunohistochemistry
the induction of the immediate early gene c-fos. Although the effect of
fenfluramine on locomotion was indistinguishable between both wild-type and 5
HT1B knock-out mice, the anorectic effect of the drug was absent in only the
knock-out mice. Furthermore, the induction of c-Fos immunoreactivity found in the
paraventricular nucleus of the hypothalamus (PVN) of wild-type mice was
substantially reduced in the knock-outs. Induction in the central amygdaloid
nucleus (CeA) and in the bed nucleus of the stria terminalis (BNST), although
robust in wild-type animals, was completely absent in knock-out animals. The
mixed 5-HT1A/1B agonist RU24969 was able to mimic both the hypophagia and c-fos
induction elicited by fenfluramine in wild-type mice, but not in the 5-HT1B knock
out mice. Our results thus demonstrate that stimulation of 5-HT1B receptors is
required for fenfluramine-induced anorexia and suggest a role for the PVN, CeA,
and BNST in mediating this effect.
PMID- 9651235
TI - Corticolimbic dopamine neurotransmission is temporally dissociated from the
cognitive and locomotor effects of phencyclidine.
AB - The behavioral syndrome produced by phencyclidine (PCP) and its analog ketamine
represents a pharmacological model for some aspects of schizophrenia. Despite the
multifaceted properties of these drugs, the main mechanism for their
psychotomimetic and cognitive-impairing effects has been thought heretofore to
involve the corticolimbic dopamine system. The present study examined the
temporal relationship between alterations in corticolimbic dopamine and glutamate
neurotransmission and two dopamine-dependent behavioral effects of PCP in the
rodent that have relevance to the clinical phenomenology, namely, impairment of
working memory, which is used to model the frontal lobe deficits associated with
schizophrenia, and hyperlocomotion, which is used as a predictor of the
propensity of a drug to elicit or exacerbate psychosis. PCP increased dopamine
and glutamate efflux in the prefrontal cortex and nucleus accumbens, as measured
by microdialysis. The increase in dopamine in both regions remained elevated well
above baseline 2.5 hr after the injection, at which time the experiment was
terminated. However, locomotor activity returned to baseline in <2 hr after
injection. Furthermore, impaired performance in a discrete trial delayed
alternation task, a rodent working memory task, was only evident up to 60 min
after PCP injection; animals tested 80 min after injection, when cortical
dopamine release was elevated at 300% of baseline, did not exhibit impaired
performance. These findings indicate that activation of dopamine
neurotransmission is not sufficient to sustain PCP-induced locomotion and
impairment of working memory. Thus, effects of PCP, including a glutamatergic
hyperstimulation, may be necessary to account for the psychotomimetic and
cognitive-impairing effects of this drug.
PMID- 9651236
TI - Quality of life for individuals with traumatic brain injury: comparison with
others living in the community.
AB - OBJECTIVES: To provide a conceptual overview of approaches to quality of life
(QOL) measurement and an extensive review of research relating to QOL after TBI;
to document subjective QOL of individuals with traumatic brain injury (TBI); to
explore how subjective QOL differs for people with TBI in comparison to
individuals with no disability (ND) and those with spinal cord injury (SCI); and
to document the perceptions of unmet important needs and the relationship between
such perceptions and subjective QOL. DESIGN: Interview-based data focusing on
current perceptions of QOL and unmet important needs, obtained from individuals
with TBI, SCI, or ND. Covariance and partial regression analyses were used to
explore group differences and to document relationships between variables.
SETTING: Individuals drawn from diverse communities across New York State.
PARTICIPANTS: TBI group: 430 individuals who identified themselves as having TBI;
SCI group: 101 individuals with spinal cord injury; ND group: 187 people who
identified themselves as having no disability. Participants were recruited
through recruitment ads in general circulation newspapers and newsletters and
through contacting a wide variety of community agencies. MAIN OUTCOME MEASURES:
Two summary QOL indicators: a Global QOL Measure based on two items tapping the
individual's emotion-based view of QOL, and a summary score adapted from
Flanagan"s Scale of Needs, reflecting the individual's perceptions of total unmet
important needs. RESULTS: Both summary QOL indicators were correlated with
demographic characteristics. Unmet important needs were stronger in the TBI group
than in the SCI and ND groups. Most areas of unmet important need were moderately
correlated with the summary QOL indicators. Analyses of covariance showed that
severity of injury was a more powerful modulator of post-TBI QOL judgments than
the mere fact of TBI. For example, those with the most severe injury (ie, loss of
consciousness [LOC] >1 month) rated their QOL similar to that in the ND group,
whereas individuals who had experienced only a brief LOC (<20 minutes) viewed
their QOL as significantly lower than that in the ND and SCI groups and lower
than other TBI severity subgroups. CONCLUSIONS: This exploration of subjective
QOL strengthens the argument that after TBI, the insider"s reaction to injury
varies greatly within the population. Thus, severity of injury strongly affects
perceptions of QOL. The use of a multimethod approach for exploring the reactions
and perceptions of QOL has proven useful in this study.
PMID- 9651237
TI - Axis I psychopathology in individuals with traumatic brain injury.
AB - OBJECTIVES: To assess the incidence, comorbidity, and patterns of resolution of
DSM-IV mood, anxiety, and substance use disorders in individuals with traumatic
brain injury (TBI). DESIGN: The Structured Clinical Interview for DSM-IV
Diagnoses (SCID) was utilized. Diagnoses were determined for three onset points
relative to TBI onset: pre-TBI, post-TBI, and current diagnosis. Contrasts of
prevalence rates with community-based samples, as well as chi-square analysis and
analysis of variance were used. Demographics considered in analyses included
gender, marital status, severity of injury, and years since TBI onset. SETTING:
Urban, suburban, and rural New York state. PARTICIPANTS: 100 adults with TBI who
were between the ages of 18 and 65 years and who were, on average, 8 years post
onset at time of interview. MAIN OUTCOME MEASURES: SCID Axis I mood diagnoses of
major depression, dysthymia, and bipolar disorder; anxiety diagnoses of panic
disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder
(PTSD), generalized anxiety disorder (GAD), and phobia; and substance use
disorders. RESULTS: Prior to TBI, a significant percentage of individuals
presented with substance use disorders. After TBI, the most frequent Axis I
diagnoses were major depression and select anxiety disorders (ie, PTSD, OCD, and
panic disorder). Comorbidity was high, with 44% of individuals presenting with
two or more Axis I diagnoses post TBI. Individuals without a pre-TBI Axis I
disorder were more likely to develop post-TBI major depression and substance use
disorders. Rates of resolution were similar for individuals regardless of
previous psychiatric histories. Major depression and substance use disorders were
more likely than were anxiety disorders to remit. CONCLUSION: TBI is a risk
factor for subsequent psychiatric disabilities. The need for proactive
psychiatric assessment and timely interventions in individuals post TBI is
indicated.
PMID- 9651238
TI - The Beck Depression Inventory: is it a suitable measure of depression for
individuals with traumatic brain injury?
AB - OBJECTIVE: This study examined the relationship between Beck Depression Inventory
(BDI) scores and current diagnosis of depression, based on The Structured
Clinical Interview for DSM-IV Diagnosis (SCID). DESIGN: Correlation. SETTING:
Community-based sample. PARTICIPANTS: 100 individuals with traumatic brain injury
(TBI) participated in this study, 25 of whom were diagnosed as depressed and 75
as not depressed at the time of interview. MAIN OUTCOME MEASURES: BDI scores,
number of symptoms reported on a symptom checklist and DSM-IV diagnosis of
depression. RESULTS: BDI symptoms correlated significantly with the SCID
diagnosis of depression (r = .30) but were more strongly related (r = .67) to the
number of non-depression-related problems reported, using the TIRR Symptom
Checklist, a list of symptoms frequently found post TBI. The BDI had low
sensitivity for discriminating depressed from nondepressed individuals
(sensitivity = 36% when specificity was set at 80%). These results suggest that
for individuals with TBI, high BDI scores may reflect hyperreactivity to post-TBI
symptoms to a greater extent than clinical depression. CONCLUSIONS: Further study
is needed to (1) understand the physiological, functional, and psychosocial
factors that are associated with depression in individuals with TBI; (2) provide
the basis for developing better measures of depression; and (3) understand how
depression is experienced after TBI.
PMID- 9651239
TI - Undiagnosed health issues in individuals with traumatic brain injury living in
the community.
AB - OBJECTIVES: To examine the self-reported prevalence of long-term health issues in
individuals with traumatic brain injury (TBI) living in the community. DESIGN: A
structured health interview. For individuals with TBI, the presence of a specific
health-related issue with onset post-TBI and currently a problem at the time of
the interview was explored. For individuals without disability, a specific health
related issue was evaluated at time of interview. For each health issue, the
proportion of individuals with TBI experiencing post-TBI onset but current
symptoms was contrasted with symptom reports of individuals without disability.
Chi-square statistical analyses were used to determine significance. For
individuals with TBI, logistic regressions were used to model the probability of
having a particular health difficulty when four covariates were examined, such as
age, gender, time since onset of TBI, and duration of loss of consciousness
(LOC). SETTING: Urban, suburban, and rural New York State. PARTICIPANTS: 338
individuals with TBI and 273 individuals without disability between the ages of
18 and 65 years. Individuals with TBI were, on average, 10 years post-onset at
the time of interview. MAIN OUTCOME MEASURES: Self-reported health issues
reflective of neuroendocrine, neurological, immunosuppression, and other health
issues. RESULTS: Chronic health issues suggestive of ongoing neuroendocrine
dysfunctions (ie, changes in hair/skin texture, body temperature changes),
neurologic difficulties (ie, headaches, seizures, balance difficulties,
spasticity, sleep disturbances, loss of urinary control), and arthritic
complaints were significantly more common in individuals with TBI. The prevalence
of many of these health-related difficulties was related to duration of LOC but
not to time since injury. Age and gender effects were found, with older women
with TBI more likely to report thyroid conditions, sleep disturbances, loss of
urinary control, and arthritic changes. Women also reported greater frequency of
headaches, colds, weight changes, and temperature changes post TBI. CONCLUSION:
Health issues reflective of neuroendocrine, neurological, and arthritic
difficulties are common long-term health issues for individuals with TBI.
Proactive patient education, ongoing health screening with appropriate medical
follow-up, and timely interventions for individuals with TBI are indicated.
Longitudinal studies are necessary to examine the natural course of post-TBI
health difficulties.
PMID- 9651240
TI - The benefits of exercise in individuals with traumatic brain injury: a
retrospective study.
AB - OBJECTIVE: This study examined the benefits of exercise. DESIGN: A retrospective
study. SETTING: A community-based sample. PARTICIPANTS: A sample of 240
individuals with traumatic brain injury (TBI) (64 exercisers and 176
nonexercisers) and 139 individuals without a disability (66 exercisers and 73
nonexercisers). MAIN OUTCOME MEASURES: Scales measuring disability and handicap.
RESULTS: It was found that the TBI exercisers were less depressed than
nonexercising individuals with TBI, TBI exercisers reported fewer symptoms, and
their self-reported health status was better than the nonexercising individuals
with TBI. There were no differences between the two groups of individuals with
TBI on measures of disability and handicap. CONCLUSIONS: The findings suggest
that exercise improves mood and aspects of health status but does affect aspects
of disability and handicap.
PMID- 9651241
TI - The effect of employment on quality of life and community integration after
traumatic brain injury.
AB - OBJECTIVES: To investigate the effect of employment on perceived quality of life
(QOL), social integration, and home and leisure activities for individuals with
traumatic brain injuries (TBIs). DESIGN: A number of demographic and injury
related variables (age at injury, time since injury, severity of injury,
education, gender, preinjury household income, and marital status) were analyzed
for their association first with employment and then with the QOL, social
integration, and home and leisure activities. Any of these variables showing
significant associations were then included along with level of employment in
three final multivariate analyses of variance (MANOVAs), again predicting QOL,
social integration, and home and leisure activities. SETTING: Urban, suburban,
and rural New York state. PARTICIPANTS: 337 adults with TBI who resided in New
York state and were between the ages of 18 and 65 years. MAIN OUTCOME MEASURES:
The Craig Handicap Assessment Capacity Technique, the Bigelow Quality of Life
Questionnaire, the Flanagan Scale of Needs (adapted), and a global QOL measure.
RESULTS: Employment showed a strong and consistent relationship with perceived
QOL, social integration within the community, and home and leisure activities.
Part-time employment may have been superior to full-time employment for
individuals with TBI: part-time workers had fewer unmet needs, were more socially
integrated, and were more engaged in home activities than full-time workers. Loss
of consciousness, as a measure of severity, was unexpectedly predictive of
diminished sense of QOL for individuals with less severe injuries. CONCLUSIONS:
Being employed contributes to one"s sense of well-being, social integration, and
pursuit of leisure and home activities. Select advantages of working part-time
for individuals with TBI were identified.
PMID- 9651242
TI - Reproductive dominance of pasture trees in a fragmented tropical forest mosaic
AB - Tropical forest fragmentation threatens biodiversity, yet basic information on
population responses for major groups such as plants is lacking. Hypervariable
genetic markers were used to reconstruct a population-level pedigree in
fragmented tropical forest for the tree Symphonia globulifera. Though seedlings
occurred only in remnant forest, the pedigree showed that most seedlings had been
produced by sequentially fewer adults in pasture, creating a genetic bottleneck.
The pedigree also implicated shifts in the foraging of animals that disperse
pollen and seed in a secondary constriction of the bottleneck. These results
suggest that tropical conservation strategies should anticipate complex, cryptic
responses to fragmentation.
PMID- 9651243
TI - Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein
in actin filament nucleation.
AB - Actin filament assembly at the cell surface of the pathogenic bacterium Listeria
monocytogenes requires the bacterial ActA surface protein and the host cell
Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin
polymerization in vitro, but pure ActA had no effect. However, when combined, the
Arp2/3 complex and ActA synergistically stimulated the nucleation of actin
filaments. This mechanism of activating the host Arp2/3 complex at the L.
monocytogenes surface may be similar to the strategy used by cells to control
Arp2/3 complex activity and hence the spatial and temporal distribution of actin
polymerization.
PMID- 9651244
TI - Congenital heart disease caused by mutations in the transcription factor NKX2-5.
AB - Mutations in the gene encoding the homeobox transcription factor NKX2-5 were
found to cause nonsyndromic, human congenital heart disease. A dominant disease
locus associated with cardiac malformations and atrioventricular conduction
abnormalities was mapped to chromosome 5q35, where NKX2-5, a Drosophila tinman
homolog, is located. Three different NKX2-5 mutations were identified. Two are
predicted to impair binding of NKX2-5 to target DNA, resulting in
haploinsufficiency, and a third potentially augments target-DNA binding. These
data indicate that NKX2-5 is important for regulation of septation during cardiac
morphogenesis and for maturation and maintenance of atrioventricular node
function throughout life.
PMID- 9651246
TI - 7500 years of prehistoric footwear from arnold research cave, missouri
AB - Accelerator mass spectrometer dating of an assemblage of fibrous and leather
footwear from Arnold Research Cave in central Missouri documents a long sequence
of shoe construction by prehistoric Midwestern peoples, beginning perhaps as
early as 8300 calendar years before the present (cal years B.P.). An earlier
fibrous sandal form dates from 8325 to 7675 cal years B.P., and later fibrous or
leather slip-ons span the period from 5575 to 1070 cal years B.P. The assemblage
adds to a growing picture of the highly varied nature of prehistoric footwear
production in the United States throughout the Holocene.
PMID- 9651245
TI - Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex.
AB - Mitochondrial cytochrome bc1 complex performs two functions: It is a respiratory
multienzyme complex and it recognizes a mitochondrial targeting presequence.
Refined crystal structures of the 11-subunit bc1 complex from bovine heart reveal
full views of this bifunctional enzyme. The "Rieske" iron-sulfur protein subunit
shows significant conformational changes in different crystal forms, suggesting a
new electron transport mechanism of the enzyme. The mitochondrial targeting
presequence of the "Rieske" protein (subunit 9) is lodged between the two "core"
subunits at the matrix side of the complex. These "core" subunits are related to
the matrix processing peptidase, and the structure unveils how mitochondrial
targeting presequences are recognized.
PMID- 9651247
TI - Dissociative recombination of HD+ in selected vibrational quantum states
AB - Rate coefficients for dissociative recombination of HD+ in selected vibrational
states have been measured by a combination of two molecular fragment imaging
methods by using the heavy-ion storage ring technique. Recombination fragment
imaging yields state-to-state reaction rates. These rates are converted to rate
coefficients by using vibrational level populations of the stored ion beam,
derived from nuclear coordinate distributions measured on extracted ions. The
results show strongly increasing rate coefficients for high vibrational
excitation, where additional dissociation routes open up, in agreement with a
theoretical calculation. Very low rate coefficients are found for certain,
isolated vibrational states.
PMID- 9651248
TI - An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA
release and delivery.
AB - A two-dimensional columnar phase in mixtures of DNA complexed with cationic
liposomes has been found in the lipid composition regime known to be
significantly more efficient at transfecting mammalian cells in culture compared
to the lamellar (LalphaC) structure of cationic liposome-DNA complexes. The
structure, derived from synchrotron x-ray diffraction, consists of DNA coated by
cationic lipid monolayers and arranged on a two-dimensional hexagonal lattice
(HIIC). Two membrane-altering pathways induce the LalphaC --> HIIC transition:
one where the spontaneous curvature of the lipid monolayer is driven negative,
and another where the membrane bending rigidity is lowered with a new class of
helper-lipids. Optical microscopy revealed that the LalphaC complexes bind stably
to anionic vesicles (models of cellular membranes), whereas the more transfectant
HIIC complexes are unstable and rapidly fuse and release DNA upon adhering to
anionic vesicles.
PMID- 9651249
TI - Pleistocene collapse of the west antarctic ice sheet
AB - Some glacial sediment samples recovered from beneath the West Antarctic ice sheet
at ice stream B contain Quaternary diatoms and up to 10(8) atoms of beryllium-10
per gram. Other samples contain no Quaternary diatoms and only background levels
of beryllium-10 (less than 10(6) atoms per gram). The occurrence of young diatoms
and high concentrations of beryllium-10 beneath grounded ice indicates that the
Ross Embayment was an open marine environment after a late Pleistocene collapse
of the marine ice sheet.
PMID- 9651250
TI - Effects of water on the alpha-beta transformation kinetics in san carlos olivine
AB - In experiments at 13.5 gigapascals and 1030 degreesC, the growth rate of
wadsleyite, which forms from transformation of olivine, was substantially
enhanced by the presence of water. Wadsleyite had a low dislocation density and
subgrain boundaries in wet runs. Water enhanced the dislocation recovery in
wadsleyite and therefore caused inelastic relaxation of the localized pressure
drop associated with the transformation, resulting in an increase of the growth
rate in wet runs. These results imply that even a small amount of water of 0. 05
weight percent can weaken wadsleyite in the mantle.
PMID- 9651251
TI - High-temperature silicate volcanism on Jupiter's moon Io.
AB - Infrared wavelength observations of Io by the Galileo spacecraft show that at
least 12 different vents are erupting lavas that are probably hotter than the
highest temperature basaltic eruptions on Earth today. In at least one case, the
eruption near Pillan Patera, two independent instruments on Galileo show that the
lava temperature must have exceeded 1700 kelvin and may have reached 2000 kelvin.
The most likely explanation is that these lavas are ultramafic (magnesium-rich)
silicates, and this idea is supported by the tentative identification of
magnesium-rich orthopyroxene in lava flows associated with these high-temperature
hot spots.
PMID- 9651252
TI - Mixer, a homeobox gene required for endoderm development.
AB - An expression cloning strategy in Xenopus laevis was used to isolate a homeobox
containing gene, Mixer, that can cause embryonic cells to form endoderm. Mixer
transcripts are found specifically in the prospective endoderm of gastrula, which
coincides with the time and place that endodermal cells become histologically
distinct and irreversibly determined. Loss-of-function studies with a dominant
inhibitory mutant demonstrate that Mixer activity is required for endoderm
development. In particular, the expression of Sox17alpha and Sox17beta, two
previously identified endodermal determinants, require Mixer function. Together,
these data suggest that Mixer is an embryonic transcription factor involved in
specifying the endodermal germ layer.
PMID- 9651253
TI - Visualization of specific B and T lymphocyte interactions in the lymph node.
AB - Early events in the humoral immune response were visualized in lymph nodes by
simultaneous tracking of antigen-specific CD4 T and B cells after immunization.
The T cells were initially activated in the T cell areas when the B cells were
still randomly dispersed in the B cell-rich follicles. Both populations then
migrated to the edges of the follicles and interacted there, resulting in CD154
dependent B cell proliferation and germinal center formation. These results
provide visual documentation of cognate T-B cell interactions and localize them
to the follicular border.
PMID- 9651255
TI - Our feet set on a new path entirely. To the transformation of primary care and
partnership with patients.
PMID- 9651256
TI - The jewel in welfare's crown. The NHS will glisten still if it retains middle
class support.
PMID- 9651254
TI - C1 transfer enzymes and coenzymes linking methylotrophic bacteria and
methanogenic Archaea.
AB - Methanogenic and sulfate-reducing Archaea are considered to have an energy
metabolism involving C1 transfer coenzymes and enzymes unique for this group of
strictly anaerobic microorganisms. An aerobic methylotrophic bacterium,
Methylobacterium extorquens AM1, was found to contain a cluster of genes that are
predicted to encode some of these enzymes and was shown to contain two of the
enzyme activities and one of the methanogenic coenzymes. Insertion mutants were
all unable to grow on C1 compounds, suggesting that the archaeal enzymes function
in aerobic C1 metabolism. Thus, methylotrophy and methanogenesis involve common
genes that cross the bacterial/archaeal boundaries.
PMID- 9651257
TI - Imagining futures for the NHS. Familiar institutions might be revamped and
strong.
PMID- 9651258
TI - On the way to Calvary. Ministers should realise the command and control model the
white paper entails.
PMID- 9651259
TI - Getting evidence into practice. Needs the right resources and the right
organisation.
PMID- 9651260
TI - Randomised trial of heroin maintenance programme for addicts who fail in
conventional drug treatments.
AB - OBJECTIVE: To evaluate an experimental heroin maintenance programme. DESIGN:
Randomised trial. SETTING: Outpatient clinic in Geneva, Switzerland. SUBJECTS:
Heroin addicts recruited from the community who were socially marginalised and in
poor health and had failed in at least two previous drug treatments.
INTERVENTION: Patients in the experimental programme (n=27) received intravenous
heroin and other health and psychosocial services. Control patients (n=24)
received any other conventional drug treatment (usually methadone maintenance).
MAIN OUTCOME MEASURES: Self reported drug use, health status (SF-36), and social
functioning. RESULTS: 25 experimental patients completed 6 months in the
programme, receiving a median of 480 mg of heroin daily. One experimental subject
and 10 control subjects still used street heroin daily at follow up (difference
44%; 95% confidence interval 16% to 71%). Health status scores that improved
significantly more in experimental subjects were mental health (0.58 SD; 0.07 to
1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and
social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also
significantly reduced their illegal income and drug expenses and committed fewer
drug and property related offences. There were no benefits in terms of work,
housing situation, somatic health status, and use of other drugs. Unexpectedly,
only nine (38%) control subjects entered the heroin maintenance programme at
follow up. CONCLUSIONS: A heroin maintenance programme is a feasible and
clinically effective treatment for heroin users who fail in conventional drug
treatment programmes. Even in this population, however, another attempt at
methadone maintenance may be successful and help the patient to stop using
injectable opioids.
PMID- 9651261
TI - Malignant spinal cord compression: prospective study of delays in referral and
treatment.
AB - OBJECTIVES: To examine the delay in presentation, diagnosis, and treatment of
malignant spinal cord compression and to define the effect of this delay on motor
and bladder function at the time of treatment. DESIGN: Prospective study of all
new patients presenting to a regional cancer centre with this condition. SETTING:
Regional cancer centre. SUBJECTS: 301 consecutive patients. MAIN OUTCOME
MEASURES: Interval from onset of symptoms to presentation and treatment, delay at
each stage of referral, and functional deterioration. RESULTS: The median (range)
delay from onset of symptoms of spinal cord compression to treatment was 14 (0
840) days. Of the total delay, 3 (0-300) days were accounted for by patients, 3
(0-330) days by general practitioners, 4 (0-794) days by the district general
hospital, and 0 (0-114) days by the treatment unit. Initial presentation to the
regional cancer centre with symptoms of malignant spinal cord compression led to
a significant reduction in delay to treatment and improved functional status at
the time of treatment. Deterioration of motor or bladder function >=1 grade
occurred at the general practice stage in 28% (57) and 18% (36) of patients, the
general hospital stage in 36% (83) and 29% (66), and the treatment unit stage in
6% (19) and 5% (15), respectively. CONCLUSIONS: Unacceptable delay in diagnosis,
investigation, and referral occurs in most patients with malignant spinal cord
compression and results in preventable loss of function before treatment.
Improvement in the outcome of such patients requires earlier diagnosis and
treatment.
PMID- 9651262
TI - Reactions of participants to the results of a randomised controlled trial:
exploratory study.
AB - OBJECTIVES: To assess views of parents of babies who participated in a neonatal
trial, about feedback of trial results. DESIGN: Qualitative analysis of
interviews. SETTING: Parents' homes. SUBJECTS: Parents of 24 surviving babies
enrolled in a UK randomised controlled trial comparing ventilatory support by
extracorporeal membrane oxygenation with conventional management. MAIN OUTCOME
MEASURES: Views about contents of results, reactions to results, effect of
hindsight, and importance of feedback. RESULTS: Information about mortality was
well understood by the parents but morbidity was less clearly reported. Even when
the content was emotionally exacting, the information was still wanted as it
removed uncertainty; provided an endpoint to difficult events; promoted further
discussion within couples; and acknowledged their contribution to answering an
important clinical question. CONCLUSIONS: Feedback of trial results to
participants should be a consideration of researchers, but a careful approach is
required. This study was based on a highly selective group of parents within a
particularly sensitive trial. More research is needed to assess the extent to
which these results can be generalised to other trials or to groups such as
bereaved parents.
PMID- 9651263
TI - Efficacy of home sampling for screening of Chlamydia trachomatis: randomised
study.
PMID- 9651265
TI - It pays to be a native
PMID- 9651264
TI - It pays to be a native
PMID- 9651267
TI - Feet on the ground
PMID- 9651266
TI - Influence of social problems on management in general practice: multipractice
questionnaire survey.
AB - OBJECTIVES: To find how often social problems influence clinical management in
general practice, how management is changed, and how the characteristics of
patients, doctors, and the doctor-patient relationship influence this management.
DESIGN: Multipractice survey of patients consulting general practitioners.
Doctors completed a questionnaire for each patient. SETTING: General practices in
Buskerud county, Norway. SUBJECTS: 1401 consecutive adult patients attending 89
general practitioners. MAIN OUTCOME MEASURES: How often management of patients
was influenced by different types of social problem and main reasons for
consultation; frequency and intercorrelation of different types of management
applied; odds ratios for social problems' influence on management, controlled for
by characteristics of doctors, patients, and their relationship. RESULTS: In 17%
of all consultations the doctors' knowledge of patients' social problems
influenced their management, stressful working conditions being the most frequent
influencing type of problem. Knowledge of social problems influenced management
more often when the doctor knew a patient well, but less often the longer a
doctor had worked in a practice. When social problems influenced management, the
commonest types of management offered were extra time for consultation (51%),
advice (42%), authorisation of sick leave (28%), and prescription of a
psychotropic drug (20%), while referral to community services was used in 2.6% of
these consultations. Prescription of a psychotropic drug was positively
correlated with use of extra time, and was made more often by female doctors.
CONCLUSIONS: Patients' social problems influenced choice of management in at
least a sixth of consultations. Prior knowledge of the patient, the doctor's time
in present practice, age and sex of the patient, and sex of the doctor
significantly influenced management of patients.
PMID- 9651268
TI - Treatment of the common cold.
PMID- 9651269
TI - The NHS's 50 anniversary. Something to celebrate. The Bevan legacy.
PMID- 9651270
TI - The NHS's 50 anniversary. Something to celebrate. As I recall.
PMID- 9651271
TI - The NHS's 50 anniversary. Something to celebrate. The BMA and the NHS.
PMID- 9651272
TI - The NHS's 50 anniversary. As others see us: views from abroad. A rational
bureaucracy in a civilised society.
PMID- 9651273
TI - The NHS's 50 anniversary. As others see us: views from abroad. A great leap for
humankind?
PMID- 9651274
TI - The NHS's 50 anniversary. As others see us: views from abroad. The importance of
social context.
PMID- 9651275
TI - The NHS's 50 anniversary. As others see us: views from abroad. Justice and health
care in a caring society.
PMID- 9651276
TI - The NHS's 50 anniversary. As others see us: views from abroad. A social
experiment that keeps adapting.
PMID- 9651277
TI - The NHS's 50 anniversary. Looking forward. The NHS: feeling well and thriving at
75.
PMID- 9651278
TI - The NHS's 50 anniversary. Clinical governance and the drive for quality
improvement in the new NHS in England.
PMID- 9651279
TI - The NHS's 50 anniversary. Will the fudge on equity sustain the NHS into the next
millennium?
PMID- 9651280
TI - The NHS's 50 anniversary. Change and resistance to change in the NHS.
PMID- 9651281
TI - Making better use of research findings.
PMID- 9651282
TI - The new NHS: message to the medical profession from the minister of health
PMID- 9651283
TI - Hypertension treatment and control in Sub-saharan Africa. Figure of $1800 per
life saved seems optimistic.
PMID- 9651284
TI - Ion channels. Ion specificity of motor end plate acetylcholine receptor.
PMID- 9651285
TI - Mistaken subdural cannulation can produce Horner's syndrome.
PMID- 9651286
TI - Incorporating patient preferences into clinical trials. Information about
patients' preference must be obtained first.
PMID- 9651287
TI - Potential biases do not affect results of waiting time study.
PMID- 9651288
TI - Temporary pacing before permanent pacing should be avoided unless essential.
PMID- 9651289
TI - People at risk of coronary heart disease should not be denied treatment with
effective drugs for purely financial reasons.
PMID- 9651290
TI - Dilemmas exist in withdrawing ventilation from dying children.
PMID- 9651291
TI - Prescribing patient information leaflets may be better than prescribing drugs.
PMID- 9651292
TI - Substitution of another opioid for morphine. Opioid toxicity should be managed
initially by decreasing the opioid dose.
PMID- 9651294
TI - Genetic counselling must be non-directive.
PMID- 9651293
TI - Consideration of short term consequences of heavier babies is important.
PMID- 9651295
TI - Private practice should mirror the NHS. Fee structure for anaesthetists in
private practice needs overhaul.
PMID- 9651297
TI - George hebbington field
PMID- 9651296
TI - Only minority of doctors supported idea of state funded health service in 1945.
PMID- 9651298
TI - Local medical committee conference
PMID- 9651299
TI - Audit in auchendreich
PMID- 9651300
TI - Cancer screening-how can we do better?
PMID- 9651301
TI - Protean elephants
PMID- 9651302
TI - Protean elephants
PMID- 9651304
TI - Delays occur in referring and treating malignant spinal cord compression
PMID- 9651303
TI - Severely addicted heroin users benefit from heroin maintenance programme
PMID- 9651305
TI - Parents involved in research welcome hearing the results
PMID- 9651306
TI - GPs management decisions are influenced by patients' social problems in 17% of
consultations
PMID- 9651307
TI - Adapt and survive: the NHS at 50
PMID- 9651308
TI - G protein-coupled receptors minireview series.
PMID- 9651309
TI - G protein-coupled receptors. I. Diversity of receptor-ligand interactions.
PMID- 9651310
TI - Differential regulation of p53-dependent and -independent proliferating cell
nuclear antigen gene transcription by 12 S E1A oncoprotein requires CBP.
AB - The tumor suppressor protein p53 and the adenoviral 12 S E1A oncoprotein are both
known to elicit their biological effects mainly by regulating the transcription
of important cellular genes. The human proliferating cell nuclear antigen (PCNA)
gene is a transcriptional target of both p53 and E1A. We have analyzed the
effects of p53 and 12 S E1A, separately as well as together, on PCNA gene
transcription. Our results showed that whereas both p53 and 12 S E1A separately
activated PCNA transcription, 12 S E1A repressed p53-mediated transcriptional
activation. Thus, 12 S E1A uses a dual strategy of transcriptional activation and
repression to take control of the cellular PCNA gene regulation. The cyclic AMP
response element in the PCNA core promoter, besides being crucial for basal
transcription, synergizes with p53 to activate transcription. The cyclic AMP
response element-binding protein (CREB)-binding protein (CBP) is an essential
component of both the transcriptional activation and repression by E1A. Our data
demonstrate for the first time that E1A can modulate CBP function to activate
PCNA transcription, while at the same time repressing p53-mediated activation by
disrupting CBP interaction with p53, thereby uncoupling PCNA transcription from
the regulatory effects of p53.
PMID- 9651311
TI - Regulation of Bcl-xl channel activity by calcium.
AB - Recent studies have demonstrated that the anti-apoptotic proteins, Bcl-2 and Bcl
xl, with the carboxyl-terminal hydrophobic domain removed, form cation-selective
channels in the lipid bilayer reconstitution system. However, the regulatory
properties of these channels are unknown. In this study, we investigated the ion
conducting properties of full-length Bcl-xl in the lipid bilayer reconstitution
system. Our findings indicate that Bcl-xl forms a cation-selective channel that
conducts sodium but not calcium and that Bcl-xl channel activity is reversibly
inhibited by luminal calcium with a half-dissociation constant of approximately
60 microM. This calcium-dependent regulation of the Bcl-xl channel provides new
insights into the roles of calcium and Bcl-2-related proteins in the programmed
cell death pathway.
PMID- 9651312
TI - Constitutive activation of photoreceptor guanylate cyclase by Y99C mutant of GCAP
1. Possible role in causing human autosomal dominant cone degeneration.
AB - Photoreceptor membrane guanylate cyclases (RetGC) are regulated by calcium
binding proteins, GCAP-1 and GCAP-2. At Ca2+ concentrations below 100 nM,
characteristic of light-adapted photoreceptors, guanylate cyclase-activating
protein (GCAPs) activate RetGC, and at free Ca2+ concentrations above 500 nM,
characteristic of dark-adapted photoreceptors, GCAPs inhibit RetGC. A mutation,
Y99C, in human GCAP-1 was recently found to be linked to autosomal dominant cone
dystrophy in a British family (Payne, A. M., Downes, S. M., Bessant, D. A. R.,
Taylor, R., Holder, G. E., Warren, M. J., Bird, A. C., and Bhattachraya, S. S.
(1998) Hum. Mol. Genet. 7, 273-277). We produced recombinant Y99C GCAP-1 mutant
and tested its ability to activate RetGC in vitro at various free Ca2+
concentrations. The Y99C mutation does not decrease the ability of GCAP-1 to
activate RetGC. However, RetGC stimulated by the Y99C GCAP-1 remains active even
at Ca2+ concentration above 1 microM. Hence, the cyclase becomes constitutively
active within the whole physiologically relevant range of free Ca2+
concentrations. We have also found that the Y99C GCAP-1 can activate RetGC even
in the presence of Ca2+-loaded nonmutant GCAPs. This is consistent with the fact
that cone degeneration was dominant in human patients who carried such mutation
(Payne, A. M., Downes, S. M., Bessant, D. A. R. , Taylor, R., Holder, G. E.,
Warren, M. J., Bird, A. C., and Bhattachraya, S. S. (1998) Hum. Mol. Genet. 7,
273-277). A similar mutation, Y104C, in GCAP-2 results in a different phenotype.
This mutation apparently does not affect Ca2+ sensitivity of GCAP-2. Instead, the
Y104C GCAP-2 stimulates RetGC less efficiently than the wild-type GCAP-2. Our
data indicate that cone degeneration associated with the Y99C mutation in GCAP-1
can be a result of constitutive activation of cGMP synthesis.
PMID- 9651313
TI - Arachidonic acid activates a proton current in the rat glutamate transporter
EAAT4.
AB - The excitatory amino acid transporter EAAT4 is expressed predominantly in
Purkinje neurons in the rat cerebellum (1-3), and it participates in postsynaptic
reuptake of glutamate released at the climbing fiber synapse (4). Transporter
mediated currents in Purkinje neurons are increased more than 3-fold by
arachidonic acid, a second messenger that is liberated following depolarization
induced Ca2+ activation of phospholipase A2 (5). In this study we demonstrate
that application of arachidonic acid to oocytes expressing rat EAAT4 increased
glutamate-induced currents to a similar extent. However, arachidonic acid did not
cause an increase in the rate of glutamate transport or in the chloride current
associated with glutamate transport but rather activated a proton-selective
conductance. These data reveal a novel action of arachidonate on a glutamate
transporter and suggest a mechanism by which synaptic activity may decrease
intracellular pH in neurons where this transporter is localized.
PMID- 9651314
TI - Three activator protein-1-binding sites bound by the Fra-2.JunD complex cooperate
for the regulation of murine laminin alpha3A (lama3A) promoter activity by
transforming growth factor-beta.
AB - Several lines of evidence suggest a role for laminin-5 in skin wound healing. We
report here that transforming growth factor-beta (TGF-beta), which elicits
various responses during cutaneous healing, stimulates transcription of the mouse
laminin alpha3A (lama3A) gene. To identify the TGF-beta-responsive elements
(TGFbeta-REs) on the lama3A promoter, we have generated a series of 5'-deletions
of the promoter upstream of the beta-galactosidase reporter gene. Transient cell
transfection assays using mouse PAM212 keratinocytes revealed that TGFbeta-REs
lie between nucleotides -297 and -54 relative to the transcription start site.
Insertion of the TGFbeta-RE in front of the unresponsive minimal SV40 promoter
conferred TGF-beta inducibility. Computer analysis of the promoter sequence
identified three canonical activator protein-1 (AP-1) sites located at
nucleotides -277 (AP-1A), -125 (AP-1B), and -69 (AP-1C). Site-directed
mutagenesis of either the AP-1A or AP-1C site did not drastically alter the basal
activity of the lama3A promoter, but reduced TGF-beta responsiveness by 50%.
Simultaneous mutation of these two AP-1 sites resulted in a 65% decline in the
response to TGF-beta, suggesting a cooperative contribution of each site to the
overall promoter activity. In contrast, mutation of the AP-1B site markedly
reduced the basal activity of the lama3A promoter, indicating that this AP-1 site
is essential for gene expression. Mobility shift assays demonstrated specific
binding of Fra-2 and JunD to the AP-1 sites, suggesting for the first time a
possible regulatory function for the Fra-2.JunD AP-1 complex in a basal
keratinocyte-specific gene.
PMID- 9651315
TI - Identification of protein-protein contacts between alpha/beta-type small, acid
soluble spore proteins of Bacillus species bound to DNA.
AB - Small, acid-soluble spore proteins (SASP) of the alpha/beta-type from several
Bacillus species were cross-linked into homodimers, heterodimers and
homooligomers with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in the
presence of linear plasmid DNA. Significant protein cross-linking was not
detected in the absence of DNA. In all four alpha/beta-type SASP examined, the
amino donor in the EDC induced amide cross-links was the alpha-amino group of the
protein. However, the carboxylate containing amino acid residues involved in
cross-linking varied. In SASP-A and SASP-C of Bacillus megaterium two conserved
glutamate residues, which form part of the germination protease recognition
sequence, were involved in cross-link formation. In SspC from Bacillus subtilis
and Bce1 from Bacillus cereus the acidic residues involved in cross-link
formation were not in the protease recognition sequence, but at a site closer to
the N terminus of the proteins. These data indicate that, although there are
likely to be subtle structural differences between different alpha/beta-type
SASP, the N-terminal regions of these proteins are involved in protein-protein
interactions while in the DNA bound state.
PMID- 9651316
TI - Functional roles of conserved amino acid residues in DNA methyltransferases
investigated by site-directed mutagenesis of the EcoRV adenine-N6
methyltransferase.
AB - All DNA methyltransferases (MTases) have similar catalytic domains containing
nine blocks of conserved amino acid residues. We have investigated by site
directed mutagenesis the function of 17 conserved residues in the EcoRV alpha
adenine-N6-DNA methyltransferase. The structure of this class of MTases has been
predicted recently. The variants were characterized with respect to their
catalytic activities and their abilities to bind to DNA and the S
adenosylmethionine (AdoMet) cofactor. Amino acids located in motifs X, I, and II
are shown to be involved in AdoMet binding (Lys16, Glu37, Phe39, and Asp58). Some
of the mutants defective in AdoMet binding are also impaired in DNA binding,
suggesting allosteric interactions between the AdoMet and DNA binding site. Asp78
(motif III), which was supposed to form a hydrogen bond to the AdoMet on the
basis of the structure predictions, turned out not to be important for AdoMet
binding, suggesting that motif III has not been identified correctly. R128A and
N130A, having mutations in the putative DNA binding domain, are unable to bind to
DNA. Residues located in motifs IV, V, VI, and VIII are involved in catalysis
(Asp193, Tyr196, Asp211, Ser229, Trp231, and Tyr258), some of them presumably in
binding the flipped target base, because mutations at these residues fail to
significantly interfere with DNA and AdoMet binding but strongly reduce
catalysis. Our results are in substantial agreement with the structure prediction
for EcoRV alpha-adenine-N6-methyltransferase and x-ray structures of other
MTases.
PMID- 9651317
TI - A membrane setting for the sorting motifs present in the adenovirus E3-13.7
protein which down-regulates the epidermal growth factor receptor.
AB - The adenovirus E3-13.7 protein interferes with endosomal protein sorting to down
regulate the epidermal growth factor receptor and related tyrosine kinase
receptors. The cytoplasmic C terminus of this protein contains three protein
sorting motifs which are related to the function of E3-13.7. In this study, the
structure of a 23-residue polypeptide corresponding to this domain was examined
using solution NMR and CD spectroscopic methods. The peptide was observed to
exist in a mostly random structural state in aqueous solution but underwent high
affinity association with dodecylphosphocholine micelles, where it adopted an
ordered structure. The affinity of this peptide for the micellar surface and the
structure of the bound peptide were independent of pH variation, surface charge,
or attachment of a myristoyl anchor to the N-terminal. Studies with phospholipid
vesicles suggested that the micellar structural results can be extrapolated to a
true lipid bilayer. On the micellar surface all three sorting motifs are closely
associated with the water/apolar interface: 72-YLRH and 87-LL lie within
interfacial amphipathic helices, while 76-HPQY is non-helical and dimples just
above the surface. These results contribute to the development of an
understanding of the basis for specificity in recognition of sorting motifs by
components of the cellular protein trafficking machinery.
PMID- 9651318
TI - A leucine-based motif mediates the endocytosis of vesicular monoamine and
acetylcholine transporters.
AB - Specific transport proteins mediate the packaging of neurotransmitters into
secretory vesicles and consequently require targeting to the appropriate
intracellular compartment. To identify residues in the neuron-specific vesicular
monoamine transporter (VMAT2) responsible for endocytosis, we examined the effect
of amino (NH2-) and carboxyl (COOH-)-terminal mutations on steady state
distribution and internalization. Deletion of a critical COOH-terminal domain
sequence (AKEEKMAIL) results in accumulation of VMAT2 at the plasma membrane and
a 50% reduction in endocytosis. Site-directed mutagenesis shows that replacement
of the isoleucine-leucine pair within this sequence by alanine-alanine alone
reduces endocytosis by 50% relative to wild type VMAT2. Furthermore, the KEEKMAIL
sequence functions as an internalization signal when transferred to the plasma
membrane protein Tac, and the mutation of the isoleucine-leucine pair also
abolishes internalization of this protein. The closely related vesicular
acetylcholine transporter (VAChT) contains a similar di-leucine sequence within
the cytoplasmic COOH-terminal domain that when mutated results in accumulation of
VAChT at the plasma membrane. The VAChT di-leucine sequence also confers
internalization when appended to two other proteins and in one of these chimeras,
conversion of the di-leucine sequence to di-alanine reduces the internalization
rate by 50%. Both VMAT2 and VAChT thus use leucine-based signals for efficient
endocytosis and as such are the first synaptic vesicle proteins known to use this
motif for trafficking.
PMID- 9651319
TI - Multiple epsilon-promoter elements participate in the developmental control of
epsilon-globin genes in transgenic mice.
AB - To delineate the regulation of the human epsilon-globin gene, we investigated
epsilon-gene expression during the development of transgenic mice carrying
constructs with epsilon-promoter truncations linked to a micro-locus control
region (microLCR). Expression levels were compared with those of microLCR epsilon
mice carrying a 2 kilobase epsilon-promoter and betaYAC controls. epsilon mRNA in
the embryonic cells of microLCR (-179)epsilon mice were as high as in microLCR
epsilon mice suggesting that the proximal epsilon-promoter contains most elements
required for epsilon-gene activation. epsilon mRNA in adult microLCR (-179)
epsilon mice was significantly lower than in the embryonic cells indicating that
elements involved in epsilon-gene silencing are contained in the proximal epsilon
promoter. Extension of the promoter sequence to -463 epsilon decreased epsilon
gene expression in the definitive erythroid cells, supporting previous evidence
that the -179 to -463epsilon region contains an epsilon-gene silencer. However,
the epsilon-gene of the microLCR(-463)epsilon mice was not silenced in the
definitive cells of fetal and adult erythropoiesis indicating that additional
silencing elements are located upstream of position -463epsilon. These results
provide in vivo evidence that multiple elements of the distal as well as the
proximal promoter contribute to epsilon-gene silencing.
PMID- 9651320
TI - Specificity of pyridinium inhibitors of the ubiquinone reduction sites in
mitochondrial complex I.
AB - Dual binding sites for pyridinium-type inhibitors in bovine heart mitochondrial
complex I have been proposed (Gluck, M. R., Krueger, M. J., Ramsay, R. R.,
Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167
3174). The marked biphasic nature of the dose-response curve for inhibition of
the enzyme by MP-6(N-methyl-4-[2-(p-tert-butylbenzyl)propyl]pyridinium) makes
this compound the first selective inhibitor of the two sites (Miyoshi, H., Inoue,
M., Okamoto, S., Ohshima, M., Sakamoto, K., and Iwamura, H. (1997) J. Biol. Chem.
272, 16176-16183). Modifications of the structure of MP-6 show that a tert-butyl
group on the benzene ring, a methyl group attached to the pyridine nitrogen atom,
para-substitution pattern in the pyridine ring, and the presence of a branched
structure in the spacer moiety are important for the selective inhibition. On the
basis of the structural specificity, we synthesized a selective inhibitor, MP-24
(N-methyl-4-[2-methyl-2-(p-tert-butylbenzyl)propyl]pyridinium), which elicits
greater selectivity. Characterization of the inhibitory behavior of MP-24
provided further strong evidence for the dual binding sites model.
PMID- 9651321
TI - Structure and transcriptional regulation of the human cystatin A gene. The 12-O
tetradecanoylphorbol-13-acetate (TPA) responsive element-2 site (-272 to -278) on
cystatin A gene is critical for TPA-dependent regulation.
AB - Cystatin A, a cysteine proteinase inhibitor, is one of the precursor proteins of
cornified cell envelope of keratinocytes and is expressed during the late stage
of keratinocyte differentiation. We have isolated and characterized the human
cystatin A gene. The cystatin A gene consists of three exons and two introns. The
first, the second, and the third exons consist of coding sequences that are 66,
102, and 126 base pairs in length, respectively. The first and the second introns
consist of 14 and 3.6 kilobase pairs, respectively. The transcription initiation
site was located 55 base pairs upstream from the first translation site. The
fragment, +77 to -2595 in the 5'-flanking region of the human cystatin A gene,
was subcloned into a chloramphenicol acetyltransferase (CAT) reporter vector. The
expression vector, p2672CAT, produced a significant CAT activity in transiently
transfected SV40-transformed human keratinocytes (SVHK cells), that were further
stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent protein kinase
C activator. Sequence analysis of the gene detected three TPA responsive elements
(TRE-1, TRE-2, and TRE-3) and one AP-2 site on the 5' upstream promoter region.
Deletion analyses of the p2672CAT vector demonstrated that TRE-2, which was
located between -272 and -278, was critical for the regulation by TPA. Gel shift
analyses revealed that c-Jun, JunD, and c-Fos bound to the TRE-2 region and that
the p2672CAT activity level was elevated by co-transfection with c-Jun and c-Fos
or with JunD and c-Fos expression vectors. Furthermore, co-transfection of SVHK
cells with the protein kinase C-alpha expression vector and the p2672CAT
expression vector also resulted in an increased CAT activity. These results
indicate that the 5'-flanking region of the human cystatin A gene confers
promoter activity and contains a TRE (TRE-2) that mediates, at least in part, the
enhanced expression of this gene by TPA.
PMID- 9651322
TI - Diversity of calcium signaling by metabotropic glutamate receptors.
AB - During prolonged application of glutamate (20 min), patterns of increase in
intracellular Ca2+ concentration ([Ca2+]i) were studied in HEK-293 cells
expressing metabotropic glutamate receptor, mGluR1alpha or mGluR5a. Stimulation
of mGluR1alpha induced an increase in [Ca2+]i that consisted of an initial
transient peak with a subsequent steady plateau or an oscillatory increase in
[Ca2+]i. The transient phase was largely attributed to Ca2+ mobilization from the
intracellular Ca2+ stores, but the sustained phase was solely due to Ca2+ influx
through the mGluR1alpha receptor-operated Ca2+ channel. Prolonged stimulation of
mGluR5a continuously induced [Ca2+]i oscillations through mobilization of Ca2+
from the intracellular Ca2+ stores. Studies on mutant receptors of mGluR1alpha
and mGluR5a revealed that the coupling mechanism in the sustained phase of Ca2+
response is determined by oscillatory/non-oscillatory patterns of the initial
Ca2+ response but not by the receptor identity. In mGluR1alpha-expressing cells,
activation of protein kinase C selectively desensitized the pathway for
intracellular Ca2+ mobilization, but the mGluR1alpha-operated Ca2+ channel
remained active. In mGluR5a-expressing cells, phosphorylation of mGluR5a by
protein kinase C, which accounts for the mechanism of mGluR5a-controlled [Ca2+]i
oscillations, might prevent desensitization and result in constant oscillatory
mobilization of Ca2+ from intracellular Ca2+ stores. Our results provide a novel
concept in which oscillatory/non-oscillatory mobilizations of Ca2+ induce
different coupling mechanisms during prolonged stimulation of mGluRs.
PMID- 9651323
TI - Herpes simplex virus inhibitor ICP47 destabilizes the transporter associated with
antigen processing (TAP) heterodimer.
AB - Chemical cross-linking of the transporter associated with antigen processing
(TAP) heterodimer was used to determine whether the herpes simplex virus
inhibitor of TAP, ICP47, induces a conformational change in TAP. Cross-linking of
TAP in cellular membranes produced a major species of approximately 220 kDa which
was comprised solely of TAP.1 and TAP.2 and most likely represents the TAP
heterodimer. Interestingly, prior treatment of TAP-containing membranes with TAP
peptide substrates stimulated the formation of the cross-linked TAP heterodimer,
whereas pretreatment of membranes with ICP47 completely blocked the formation of
the cross-linked heterodimer. These data suggest that suitable substrates for TAP
stabilize the TAP heterodimer, whereas ICP47 destabilizes the heterodimer. The
results indicate that subtle conformational changes occur in the TAP heterodimer
upon the binding of peptides and the inhibitor ICP47 and that ICP47 has a
deleterious effect on TAP heterodimer structure, in addition to its role as a
potent blocker of substrate binding to TAP.
PMID- 9651324
TI - Enhanced cholesterol efflux by tyrosyl radical-oxidized high density lipoprotein
is mediated by apolipoprotein AI-AII heterodimers.
AB - Myeloperoxidase secreted by phagocytes in the artery wall may be a catalyst for
lipoprotein oxidation. High density lipoprotein (HDL) oxidized by peroxidase
generated tyrosyl radical has a markedly enhanced ability to deplete cultured
cells of cholesterol. We have investigated the structural modifications in
tyrosylated HDL responsible for this effect. Spherical reconstituted HDL (rHDL)
containing the whole apolipoprotein (apo) fraction of tyrosylated HDL reproduced
the ability of intact tyrosylated HDL to enhance cholesterol efflux from
cholesterol-loaded human fibroblasts when reconstituted with the whole lipid
fraction of either HDL or tyrosylated HDL. Free apoAI or apoAII showed no
increased capacity to induce cholesterol efflux from cholesterol-loaded
fibroblasts following oxidation by tyrosyl radical, either in their lipid-free
forms or in rHDL. The product of oxidation of a mixture of apoAI and apoAII (1:1
molar ratio) by tyrosyl radical, however, reproduced the enhanced ability of
tyrosylated HDL to induce cholesterol efflux when reconstituted with the whole
lipid fraction of HDL. HDL containing only apoAI or apoAII showed no enhanced
ability to promote cholesterol efflux following oxidation by tyrosyl radical,
whereas HDL containing both apoAI and apoAII did. rHDL containing apoAI
apoAIImonomer and apoAI-(apoAII)2 heterodimers showed a markedly increased
ability to prevent the accumulation of LDL-derived cholesterol mass by sterol
depleted fibroblasts compared with other apolipoprotein species of tyrosylated
HDL. These results indicate a novel product of HDL oxidation, apoAI-apoAII
heterodimers, with a markedly enhanced capacity to deplete cells of the
regulatory pool of free cholesterol and total cholesterol mass. The recent
observation of tyrosyl radical-oxidized LDL in vivo suggests that a similar
modification of HDL would significantly enhance its ability to deplete peripheral
cells of cholesterol in the first step of reverse cholesterol transport.
PMID- 9651325
TI - Biosynthesis of branched polylactosaminoglycans. Embryonal carcinoma cells
express midchain beta1,6-N-acetylglucosaminyltransferase activity that generates
branches to preformed linear backbones.
AB - Two types of beta1,6-GlcNAc transferases (IGnT6) are involved in in vitro
branching of polylactosamines: dIGnT6 (distally acting), transferring to the
penultimate galactose residue in acceptors like GlcNAcbeta1-3Galbeta1
4GlcNAcbeta1-R, and cIGnT6 (centrally acting), transferring to the midchain
galactoses in acceptors of the type (GlcNAcbeta1-3)Galbeta1-4GlcNAcbeta1
3Galbeta1-+ ++4GlcNAcbeta1-R. The roles of the two transferases in the
biosynthesis of branched polylactosamine backbones have not been clearly
elucidated. We report here that cIGnT6 activity is expressed in human (PA1) and
murine (PC13) embryonal carcinoma (EC) cells, both of which contain branched
polylactosamines in large amounts. In the presence of exogenous UDP-GlcNAc,
lysates from both EC cells catalyzed the formation of the branched
pentasaccharide Galbeta1-4GlcNAcbeta1-3(GlcNAcbeta1-6)Galbeta1-4 GlcNAc from the
linear tetrasaccharide Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc. The PA1 cell
lysates were shown to also catalyze the formation of the branched
heptasaccharides Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1-3(+ ++GlcNAcbeta1
6)Galbeta1 -4GlcNAc and Galbeta1-4GlcNAcbeta1-3(GlcNAcbeta1-6)Galbeta1-+
++4GlcNAcbeta1-3Galbeta1 -4GlcNAc from the linear hexasaccharide Galbeta1
4GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1- 3Galbeta1-4GlcNAc in reactions
characteristic to cIGnT6. By contrast, dIGnT6 activity was not detected in the
lysates of the two EC cells that were incubated with UDP-GlcNAc and the acceptor
trisaccharide GlcNAcbeta1-3Galbeta1-4GlcNAc. Hence, it appears likely that
cIGnT6, rather than dIGnT6 is responsible for the synthesis of the branched
polylactosamine chains in these cells.
PMID- 9651326
TI - Truncation of amino acids 12-128 causes deregulation of the phosphatase activity
of the sensor kinase KdpD of Escherichia coli.
AB - The kdpFABC operon, which encodes the structural genes for the high affinity K+
transport complex KdpFABC, is regulated by the sensor kinase KdpD and the
response regulator KdpE. KdpD is a bifunctional enzyme catalyzing the
autophosphorylation by ATP and the dephosphorylation of the corresponding
response regulator KdpE. Here, we demonstrate that the phosphatase activity of
KdpD is dependent on ATP, whereas GTP, ITP, CTP, ADP, and GDP have no effect. The
phosphatase activity requires only ATP binding, because nonhydrolyzable analogs
(adenosine-5'-[gamma-thio]triphosphate and adenosine-5'-[beta,gamma
imido]triphosphate) work as well. However, KdpD proteins missing amino acids 12
128 are characterized by a phosphatase activity that is independent of ATP. These
proteins are still able to respond to K+ starvation, but an increase in
osmolarity is no longer sensed. Comparison of different KdpD sequences reveals a
conserved motif in this amino acid region that is very similar to a classical ATP
binding site (Walker A motif). Replacement of the conserved Gly37, Lys38, and
Thr39 residues in the consensus ATP-binding sequence results in a KdpD protein
that causes a kdpFABC expression pattern comparable with that seen with KdpD
proteins missing amino acids 12-128. However, in vitro phosphatase activity is
comparable with that of wild-type KdpD. These results suggest that amino acids 12
128 of KdpD are important for its activity and that an additional ATP-binding
site in the N-terminal region seems to be involved in modulation of the
phosphatase activity.
PMID- 9651327
TI - Structure-function relationships in membrane segment 5 of the yeast Pma1 H+
ATPase.
AB - Membrane segment 5 (M5) is thought to play a direct role in cation transport by
the sarcoplasmic reticulum Ca2+-ATPase and the Na+, K+-ATPase of animal cells. In
this study, we have examined M5 of the yeast plasma membrane H+-ATPase by alanine
scanning mutagenesis. Mutant enzymes were expressed behind an inducible heat
shock promoter in yeast secretory vesicles as described previously (Nakamoto, R.
K., Rao, R., and Slayman, C. W. (1991) J. Biol. Chem. 266, 7940-7949). Three
substitutions (R695A, H701A, and L706A) led to misfolding of the H+-ATPase as
evidenced by extreme sensitivity to trypsin; the altered proteins were arrested
in biogenesis, and the mutations behaved genetically as dominant lethals. The
remaining mutants reached the secretory vesicles in sufficient amounts to be
characterized in detail. One of them (Y691A) had no detectable ATPase activity
and appeared, based on trypsinolysis in the presence and absence of ligands, to
be blocked in the E1-to-E2 step of the reaction cycle. Alanine substitution at an
adjacent position (V692A) had substantial ATPase activity (54%), but was likewise
affected in the E1-to-E2 step, as evidenced by shifts in its apparent affinity
for ATP, H+, and orthovanadate. Among the mutants that were sufficiently active
to be assayed for ATP-dependent H+ transport by acridine orange fluorescence
quenching, none showed an appreciable defect in the coupling of transport to ATP
hydrolysis. The only residue for which the data pointed to a possible role in
cation liganding was Ser-699, where removal of the hydroxyl group (S699A and
S699C) led to a modest acid shift in the pH dependence of the ATPase. This change
was substantially smaller than the 13-30-fold decrease in K+ affinity seen in
corresponding mutants of the Na+, K+-ATPase (Arguello, J. M., and Lingrel, J. B
(1995) J. Biol. Chem. 270, 22764-22771). Taken together, the results do not give
firm evidence for a transport site in M5 of the yeast H+-ATPase, but indicate a
critical role for this membrane segment in protein folding and in the
conformational changes that accompany the reaction cycle. It is therefore worth
noting that the mutationally sensitive residues lie along one face of a putative
alpha-helix.
PMID- 9651328
TI - Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic
similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin
aldolase.
AB - An open reading frame located at 69.0 kilobases on the Escherichia coli
chromosome was shown to code for dihydroneopterin aldolase, catalyzing the
conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the
biosynthetic pathway of tetrahydrofolate. The gene was subsequently designated
folB. The FolB protein shows 30% identity to the paralogous dihydroneopterin
triphosphate epimerase, which is specified by the folX gene located at 2427
kilobases on the E. coli chromosome. The folX and folB gene products were both
expressed to high yield in recombinant E. coli strains, and the recombinant
proteins were purified to homogeneity. Both enzymes form homo-octamers. Aldolase
can use L-threo-dihydroneopterin and D-erythro-dihydroneopterin as substrates for
the formation of 6-hydroxymethyldihydropterin, but it can also catalyze the
epimerization of carbon 2' of dihydroneopterin and dihydromonapterin at
appreciable velocity. Epimerase catalyzes the epimerization of carbon 2' in the
triphosphates of dihydroneopterin and dihydromonapterin. However, the enzyme can
also catalyze the cleavage of the position 6 side chain of several pteridine
derivatives at a slow rate. Steady-state kinetic parameters are reported for the
various enzyme-catalyzed reactions. We propose that the polarization of the 2'
hydroxy group of the substrate could serve as the initial reaction step for the
aldolase as well as for the epimerase activity. A deletion mutant obtained by
targeting the folX gene of E. coli has normal growth properties on complete
medium as well as on minimal medium. Thus, the physiological role of the E. coli
epimerase remains unknown. The open reading frame ygiG of Hemophilus influenzae
specifies a protein with the catalytic properties of an aldolase. However, the
genome of H. influenzae does not specify a dihydroneopterin-triphosphate
epimerase.
PMID- 9651329
TI - Modulation of DNA binding of a tramtrack zinc finger peptide by the
metallothionein-thionein conjugate pair.
AB - The ability of metallothionein (MT) to modulate DNA binding by a two-finger
peptide of Tramtrack (TTK), a CCHH zinc transcription factor, was investigated
using metal-bound and metal-deficient forms of rabbit MT-2 and the TTK peptide.
Thionein inhibited DNA binding by zinc-bound TTK, and Zn-MT restored DNA-binding
by zinc-deficient apo-TTK. "Free" zinc at low concentrations was as effective as
Zn-MT in restoring DNA binding by apopeptide but was inhibitory at concentrations
equal to zinc bound to 2 mol eq and higher of Zn-MT. Substitution of cadmium for
zinc reduced the affinity of the peptide for its DNA binding site. This effect
was reversed by incubation with Zn-MT. The circular dichroic spectra of the TTK
peptide indicated that zinc removal resulted in loss of alpha-helical structures,
which are sites of DNA contact points. Reconstitution with cadmium resulted in
stoichiometric substitution of 2 mol of Cd/mol of peptide but not recovery of
alpha-helical structures. Incubation of Cd-TTK with Zn-MT restored the secondary
structure expected for zinc-bound TTK. The ability of Zn-MT and thionein to
restore or inhibit DNA-binding by TTK was associated with effects on the
metallation status of the peptide and related alterations in its secondary
structure.
PMID- 9651330
TI - Matrilin-3 forms disulfide-linked oligomers with matrilin-1 in bovine epiphyseal
cartilage.
AB - A comparison of noncollagenous matrix proteins from different types of bovine
cartilage by SDS-polyacrylamide gel electrophoresis showed a prominent 240-kDa
component in extracts of epiphyseal but not tracheal tissue. On amino-terminal
sequence analysis, it gave two sequences. One matched the NH2 terminus of
cartilage matrix protein (CMP) as reported for tracheal cartilage. The other did
not match any known protein sequence. Further analysis of the 240-kDa protein
after reduction of disulfides resolved two bands on SDS-polyacrylamide gel
electrophoresis. Isolation and sequence analysis of tryptic peptides confirmed
that one was bovine CMP and the other a CMP homolog. A data base search
identified the latter as matrilin-3, a molecule recently predicted from human and
mouse cDNA sequences (Wagener, R., Kobbe, B., and Paulsson, M. (1997) FEBS Lett.
413, 129-134). Matrilin-3 and CMP (matrilin-1) were prominent in equimolar
amounts in fetal bovine epiphyseal cartilage and absent from adult articular
cartilage. Adult tracheal cartilage contained almost exclusively CMP. Although
the mechanism of polymeric assembly is unknown, the matrilin-3 chain appears to
function in the matrix linked to matrilin-1 in the form of disulfide-bonded
heteromeric molecules. The results indicate a molecular stoichiometry of
(matrilin-1)2(matrilin-3)2.
PMID- 9651331
TI - UV-B-induced differential transcription of psbA genes encoding the D1 protein of
photosystem II in the Cyanobacterium synechocystis 6803.
AB - UV-B irradiation of intact Synechocystis sp. PCC 6803 cells results in the loss
of photosystem II activity, which can be repaired via de novo synthesis of the D1
(and D2) reaction center subunits. In this study, we investigated the effect of
UV-B irradiation on the transcription of the psbA2 and psbA3 genes encoding
identical D1 proteins. We show that UV-B irradiation increases the level of psbA2
mRNA 2-3-fold and, more dramatically, it induces a 20-30-fold increase in the
accumulation of the psbA3 mRNA even at levels of irradiation too low to produce
losses of either photosystem II activity or D1 protein. The induction of psbA3
transcript accumulation is specific for UV-B light (290-330 nm). Low intensity UV
A emission (330-390 nm) and white light induce only a small, at most, 2-3-fold
enhancement, whereas no effect of blue light was observed. Expression patterns of
chimeric genes containing the promoter regions of the psbA2, psbA3 genes fused to
the firefly luciferase (luc) reporter gene indicate that (i) transcription of
psbA2/luc and psbA3/luc transgenes was elevated, similarly to that of the
endogenous psbA genes, by UV-B irradiation, and that (ii) a short, 80-base pair
psbA3 promoter fragment is sufficient to maintain UV-B-induced transcription of
the luc reporter gene. Furthermore, our findings indicate that UV-B-induced
expression of the psbA2 and psbA3 genes is a defense response against UV-B
stress, which is regulated, at least, partially at the level of transcription and
does not require active electron transport.
PMID- 9651332
TI - Hydrolysis of phosphodiesters through transformation of the bacterial
phosphotriesterase.
AB - The phosphotriesterase from Pseudomonas diminuta catalyzes the hydrolysis of a
wide array of phosphotriesters and related phosphonates, including
organophosphate pesticides and military nerve agents. It has now been shown that
this enzyme can also catalyze the hydrolysis of phosphodiesters, albeit at a
greatly reduced rate. However, the enzymatic hydrolysis of ethyl-4-nitrophenyl
phosphate (compound I) by the wild-type enzyme was >10(8) times faster than the
uncatalyzed reaction (kcat = 0.06 s-1 and Km = 38 mM). Upon the addition of
various alkylamines to the reaction mixture, the kcat/Km for the phosphodiester
(compound I) increased up to 200-fold. Four mutant enzymes of the
phosphotriesterase were constructed in a preliminary attempt to improve
phosphodiester hydrolysis activity of the native enzyme. Met-317, which is
thought to reside in close proximity to the pro-S-ethoxy arm of the paraoxon
substrate, was mutated to arginine, alanine, histidine, and lysine. These mutant
enzymes showed slight improvements in the catalytic hydrolysis of organophosphate
diesters. The M317K mutant enzyme displayed the most improvement in catalytic
activity (kcat = 0.34 s-1 and Km = 30 mM). The M317A mutant enzyme catalyzed the
hydrolysis of the phosphodiester (compound I) in the presence of alkylamines up
to 200 times faster than the wild-type enzyme in the absence of added amines. The
neutralization of the negative charge on the oxygen atom of the phosphodiester by
the ammonium cation within the active site is thought to be responsible for the
rate enhancement by these amines in the hydrolytic reaction. These results
demonstrate that an active site optimized for the hydrolysis of organophosphate
triesters can be made to catalyze the hydrolysis of organophosphate diesters.
PMID- 9651333
TI - Characterization of aggrecan retained and lost from the extracellular matrix of
articular cartilage. Involvement of carboxyl-terminal processing in the
catabolism of aggrecan.
AB - The catabolism of aggrecan in bovine articular cartilage explants is
characterized by the release into the culture medium of high molecular weight
aggrecan fragments, generated by the proteolytic cleavage of the core protein
between residues Glu373 and Ala374 within the interglobular domain. In this
study, the position of the carboxyl-terminus of these aggrecan fragments, as well
as a major proteolytically shortened aggrecan core protein present in cartilage
matrix, have been deduced by characterizing the peptides generated by the
reaction of aggrecan core protein peptides with cyanogen bromide. It was shown
that two out of three such peptide fragments having an amino terminus starting at
Ala374 have their carboxyl terminus located within the chondroitin sulfate 1
domain. The third and largest aggrecan core protein peptide, with an amino
terminus starting at Ala374, has a carboxyl terminus in a region of core protein
between the chondroitin sulfate 1 domain and the chondroitin sulfate 2 domain.
The carboxyl terminus of this peptide appeared to be the same as that of the
proteolytically degraded aggrecan core protein, which is retained within the
extracellular matrix of the tissue. Another two aggrecan fragments recovered from
the medium of explant cultures with amino-terminal sequences in the chondroitin
sulfate 2 domain at Ala1772 and Leu1872 were shown to have their carboxyl termini
within the G3 globular domain. These results suggest that the catabolism of
aggrecan between residues Glu373 and Ala374 in the interglobular domain by the
putative proteinase, aggrecanase, may be dependent on prior proteolytic
processing within the carboxyl-terminal region of the core protein.
PMID- 9651334
TI - Antichymotrypsin interaction with chymotrypsin. Reactions following encounter
complex formation.
AB - Serpins, serine proteinase inhibitors, form enzymatically inactive, 1:1 complexes
(denoted E*I*) with their target proteinases, that only slowly release I*, in
which the P1-P1' linkage is cleaved. Recently we presented evidence that the
serpin antichymotrypsin (ACT, I) reacts with the serine proteinase chymotrypsin
(Chtr, E) to form an E*I* complex via a three-step mechanism, E + I <==> E .I
<==> EI' <==> E*I* in which EI', which retains the P1-P1' linkage, is formed in a
partly or largely rate-determining step, depending on temperature (O'Malley, K.
H, Nair, S. A., Rubin, H., and Cooperman, B. S. (1997) J. Biol. Chem. 272, 5354
5359). Here we extend these studies through the introduction of a new assay for
the formation of the postcomplex fragment, corresponding to ACT residues 359 (the
P1' residue) to 398 (the C terminus), coupled with rapid quench flow kinetic
analysis. We show that the E.I encounter complex of wild type-rACT and Chtr forms
both E*I* and postcomplex fragment with the same rate constant, so that both
species arise from EI' conversion to E*I*. These results support our earlier
conclusion that the P1-P1' linkage is preserved in EI' and imply that E*I*
corresponds to a covalent adduct of E and I, either acyl enzyme or the
tetrahedral intermediate formed by water attack on acyl enzyme. Furthermore, we
show that the A347R (P12) variant of rACT, which is a substrate rather than an
inhibitor of Chtr, has a rate constant for postcomplex fragment formation from
the E.I complex very similar to that observed for WT-rACT, implying that EI' is
the common intermediate from which partitioning to inhibitor and substrate
pathways occurs. These results are used to elaborate a proposed scheme for ACT
interaction with Chtr that is considered in the light of relevant results from
studies of other serpin-serine proteinase pairs.
PMID- 9651335
TI - Zinc cluster proteins Leu3p and Uga3p recognize highly related but distinct DNA
targets.
AB - Members of the family of fungal zinc cluster DNA-binding proteins possess 6
highly conserved cysteines that bind to two zinc atoms forming a structure
(Zn2Cys6) that is required for recognition of specific DNA sequences. Many zinc
cluster proteins have been shown to bind as homodimers to a pair of CGG triplets
oriented either as direct (CGG NX CGG), inverted (CGG NX CCG), or everted repeats
(CCG NX CGG), where N indicates nucleotides. Variation in the spacing between the
CGG triplets also contributes to the diversity of sites recognized. For example,
Leu3p binds to the everted sequence CCG N4 CGG with a strict requirement for a 4
base pair spacing. Here, we show that another member of the family, Uga3p,
recognizes the same DNA motif as Leu3p. However, these transcription factors have
distinct DNA targets. We demonstrate that additional specificity of binding is
provided by nucleotides located between the two everted CGG triplets. Altering
the 4 nucleotides between to the two everted CGG triplets switches the
specificity from a Uga3p site to a Leu3p site in both in vitro and in vivo
assays. Thus, our results identify a new mechanism that expands the repertoire of
DNA targets of the family of zinc cluster proteins. These experiments provide a
model for discrimination between targets of zinc cluster proteins.
PMID- 9651336
TI - Stimulation of type 1 and type 8 Ca2+/calmodulin-sensitive adenylyl cyclases by
the Gs-coupled 5-hydroxytryptamine subtype 5-HT7A receptor.
AB - The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays an important
regulatory role in developing and adult nervous systems. With the exception of
the 5-HT3 receptor, all of the cloned serotonin receptors belong to the G protein
coupled receptor superfamily. Subtypes 5-HT6 and 5-HT7 couple to stimulation of
adenylyl cyclases through Gs and display high affinities for antipsychotic and
antidepressant drugs. In the brain, mRNA for 5-HT6 is found at high levels in the
hippocampus, striatum, and nucleus accumbens. 5-HT7 mRNA is most abundant in the
hippocampus, neocortex, and hypothalamus. To better understand how serotonin
might control cAMP levels in the brain, we coexpressed 5-HT6 or 5-HT7A receptors
with specific isoforms of adenylyl cyclase in HEK 293 cells. The 5-HT6 receptor
functioned as a typical Gs-coupled receptor in that it stimulated AC5, a Gs
sensitive adenylyl cyclase, but not AC1 or AC8, calmodulin (CaM)-stimulated
adenylyl cyclases that are not activated by Gs-coupled receptors in vivo.
Surprisingly, serotonin activation of 5-HT7A stimulated AC1 and AC8 by increasing
intracellular Ca2+. 5-HT also increased intracellular Ca2+ in primary neuron
cultures. These data define a novel mechanism for the regulation of intracellular
cAMP by serotonin.
PMID- 9651337
TI - Reactive oxygen species- and dimerization-induced activation of apoptosis signal
regulating kinase 1 in tumor necrosis factor-alpha signal transduction.
AB - Reactive oxygen species (ROS) have been implicated in the induction of apoptosis
by tumor necrosis factor-alpha (TNFalpha) and other cytotoxic insults, although
the molecule(s) regulated by ROS in TNFalpha signaling have not been identified.
Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated
protein kinase kinase kinase (MAPKKK) superfamily that has been shown to be
activated during TNFalpha-induced apoptosis. ASK1 increases apoptosis when
overexpressed, but the mechanism of ASK1 activation and the mechanisms of ASK1
induced apoptosis are unclear. We now report that hydrogen peroxide induces the
activation of ASK1 in 293 cells. TNFalpha-induced activation of ASK1 was
inhibited by antioxidants. Hydrogen peroxide-induced apoptosis was markedly
enhanced by the expression of ASK1. These results suggest that TNFalpha-induced
activation of ASK1 is mediated by ROS. We also examined how ASK1 activity is
regulated by ROS. We found that ASK1 formed dimers or higher order oligomers in
293 cells. TNFalpha or hydrogen peroxide treatment increased the dimeric form of
ASK1, and pretreatment with N-acetylcysteine decreased it. Furthermore, synthetic
dimerization of an ASK1-gyrase B fusion protein by coumermycin resulted in
substantial activation of ASK1, suggesting that dimerization of ASK1 is
sufficient for its activation. These results taken together suggest that TNFalpha
causes ASK1 activation via ROS-mediated dimerization of ASK1.
PMID- 9651338
TI - Apolipoprotein E2 reduces the low density lipoprotein level in transgenic mice by
impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich
lipoproteins.
AB - Apolipoprotein (apo) E2 is often associated with low levels of low density
lipoprotein (LDL) cholesterol and high levels of plasma triglycerides in humans.
Mice expressing apoE2 also have low LDL levels. To evaluate the possible role of
the LDL receptor in the cholesterol-lowering effect of apoE2, we bred transgenic
mice expressing low levels of apoE2 with LDL receptor-null mice (hE2(+/0), LDLR-/
). Even in the absence of the LDL receptor, plasma total and LDL cholesterol
levels decreased progressively with increasing levels of plasma apoE2. At plasma
apoE2 levels >20 mg/dl, LDL cholesterol was approximately 45% lower than in LDLR
/- mice. Thus, the LDL cholesterol-lowering effect of apoE2 is independent of the
LDL receptor. In contrast, plasma triglyceride levels increased (mostly in very
low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL))
progressively as apoE2 levels increased. At plasma apoE2 levels >20 mg/dl,
triglycerides were approximately 150% higher than in LDLR-/- mice. Furthermore,
in apoE-null mice (hE2(+/0), mE-/-), apoE2 levels also correlated positively with
plasma triglyceride levels, suggesting impaired lipolysis in both hE2(+/0),LDLR-/
and hE2(+/0),mE-/- mice. Incubating VLDL or IDL from the hE2(+/0),LDLR-/- or the
hE2(+/0),mE-/- mice with mouse postheparin plasma inhibited lipoprotein lipase
mediated lipolysis of apoE2-containing VLDL and IDL by approximately 80 and
approximately 70%, respectively, versus normal VLDL and IDL. This observation was
confirmed by studies with triglyceride-rich emulsion particles, apoE2, and
purified lipoprotein lipase. Furthermore, apoE2-containing VLDL had much less
apoC-II than normal VLDL. Adding apoC-II to the incubation partially corrected
the apoE2-impaired lipolysis in apoE2-containing VLDL or IDL and corrected it
completely in apoE2-containing emulsion particles. Thus, apoE2 lowers LDL
cholesterol by impairing lipoprotein lipase-mediated lipolysis of triglyceride
rich lipoproteins (mostly by displacing or masking apoC-II). Furthermore, the
effects of apoE2 on both plasma cholesterol and triglyceride levels are dose
dependent and act via different mechanisms. The increase in plasma cholesterol
caused by apoE2 is due mostly to impaired clearance, whereas the increase in
plasma triglycerides is caused mainly by apoE2-impaired lipolysis of triglyceride
rich lipoproteins.
PMID- 9651339
TI - Evidence that IRS-2 phosphorylation is required for insulin action in
hepatocytes.
AB - Insulin receptor substrates (IRSs) are tyrosine-phosphorylated following
stimulation with insulin, insulin-like growth factors (IGFs), and interleukins. A
key question is whether different IRSs play different roles to mediate insulin's
metabolic and growth-promoting effects. In a novel system of insulin receptor
deficient hepatocytes, insulin fails to (i) stimulate glucose phosphorylation,
(ii) enhance glycogen synthesis, (iii) suppress glucose production, and (iv)
promote mitogenesis. However, insulin's ability to induce IRS-1 and gab-1
phosphorylation and binding to phosphatidylinositol (PI) 3-kinase is unaffected,
by virtue of the compensatory actions of IGF-1 receptors. In contrast,
phosphorylation of IRS-2 and generation of IRS-2/PI 3-kinase complexes are
markedly reduced. Thus, absence of insulin receptors selectively reduces IRS-2,
but not IRS-1 phosphorylation, and the impairment of IRS-2 activation is
associated with lack of insulin effects. To address whether phosphorylation of
additional IRSs is also affected, we analyzed phosphotyrosine-containing proteins
in PI 3-kinase immunoprecipitates from insulin-treated cells. However, these
experiments indicate that IRS-1 and IRS-2 are the main PI 3-kinase-bound proteins
in hepatocytes. These data identify IRS-2 as the main effector of both the
metabolic and growth-promoting actions of insulin through PI 3-kinase in
hepatocytes, and IRS-1 as the main substrate mediating the mitogenic actions of
IGF-1 receptors.
PMID- 9651340
TI - Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line.
Involvement of arachidonic acid metabolism.
AB - The study of signaling cascades and of functional interactions between 5
hydroxytryptamine (5-HT) receptor pathways with heterogenous brain cell
populations remains an arduous task. We took advantage of a serotonergic cell
line to elucidate cross-talks between 5-HT receptors and to demonstrate the
involvement of two 5-HT2 receptor subtypes in the regulation of 5-HT1B/1D
function. The inducible 1C11 cell line has the unique property of acquiring
within 4 days a complete serotonergic phenotype (1C11* cells), including three 5
HT receptors. 5-HT1B/1D and 5-HT2B receptors are expressed since day 2 of the
serotonergic differentiation while 5-HT2A receptors are induced at day 4. We
first established that 5-HT2B receptors are coupled with the phospholipase A2
(PLA2)-mediated release of arachidonic acid (AA) and that the activation of 5
HT2B receptors in 1C11*d2 cells inhibits the 5-HT1B/1D receptor function via a
cyclooxygenase-dependent AA metabolite. At day 4, this 5-HT2B-mediated inhibition
of the 5-HT1B/1D function can be blocked upon concomitant 5-HT2A activation
although a 5-HT2A/PLA2 positive coupling was evidenced. This suggests the
existence in 1C11*d4 cells of pathway(s) for 5-HT2A receptors, distinct from PLC
and PLA2. Finally, this study reveals the antagonistic roles of 5-HT2A and 5-HT2B
receptors in regulating the function of 5-HT1B/1D, a receptor involved in
neuropsychiatric disorders and migraine pathogenesis.
PMID- 9651341
TI - Endocytosis of the glucose transporter GLUT4 is mediated by the GTPase dynamin.
AB - To study the role of the GTPase dynamin in GLUT4 intracellular recycling, we have
overexpressed dynamin-1 wild type and a GTPase-negative mutant (K44A) in primary
rat adipose cells. Transfection was accomplished by electroporation using an
hemagglutinin (HA)-tagged GLUT4 as a reporter protein. In cells expressing HA
GLUT4 alone, insulin results in an approximately 7-fold increase in cell surface
anti-HA antibody binding. Studies with wortmannin indicate that the kinetics of
HA-GLUT4-trafficking parallel those of the native GLUT4 and in addition, that
newly synthesized HA-GLUT4 goes to the plasma membrane before being sorted into
the insulin-responsive compartments. Short term (4 h) coexpression of dynamin
K44A and HA-GLUT4 increases the amount of cell surface HA-GLUT4 in both the basal
and insulin-stimulated states. Under conditions of maximal expression of dynamin
K44A (24 h), most or all of the intracellular HA-GLUT4 appears to be present on
the cell surface in the basal state, and insulin has no further effect.
Measurements of the kinetics of HA-GLUT4 endocytosis show that dynamin-K44A
blocks internalization of the glucose transporters. In contrast, expression of
dynamin wild type decreases the amount of cell surface HA-GLUT4 in both the basal
and insulin-stimulated states. These data demonstrate that the endocytosis of
GLUT4 is largely mediated by processes which require dynamin.
PMID- 9651342
TI - Directed mutations in the poorly defined region of porcine liver fructose-1,6
bisphosphatase significantly affect catalysis and the mechanism of AMP
inhibition.
AB - Asn64, Asp68, Lys71, Lys72, and Asp74 of porcine liver fructose-1, 6
bisphosphatase (FBPase) are conserved residues and part of a loop for which no
electron density has been observed in crystal structures. Yet mutations of the
above dramatically affect catalytic rates and/or AMP inhibition. The Asp74 -->
Ala and Asp74 --> Asn mutant enzymes exhibited 50,000- and 2,000-fold reductions,
respectively, in kcat relative to wild-type FBPase. The pH optimum for the
catalytic activity of the Asp74 --> Glu, Asp68 --> Glu, Asn64 --> Gln, and Asn64
-> Ala mutant enzymes shifted from pH 7.0 (wild-type enzyme) to pH 8.5, whereas
the Lys71 --> Ala mutant and Lys71,72 --> Met double mutant had optimum activity
at pH 7.5. Mg2+ cooperativity, Km for fructose 1,6-bisphosphate, and Ki for
fructose 2,6-bisphosphate were comparable for the mutant and wild-type enzymes.
Nevertheless, for the Asp74 --> Glu, Asp68 --> Glu, Asn64 --> Gln, and Asn64 -->
Ala mutants, the binding affinity for Mg2+ decreased by 40-125-fold relative to
the wild-type enzyme. In addition, the Asp74 --> Glu and Asn64 --> Ala mutants
exhibited no AMP cooperativity, and the kinetic mechanism of AMP inhibition with
respect to Mg2+ was changed from competitive to noncompetitive. The double
mutation Lys71,72 --> Met increased Ki for AMP by 175-fold and increased Mg2+
affinity by 2-fold relative to wild-type FBPase. The results reported here
strongly suggest that loop 51-72 is important for catalytic activity and the
mechanism of allosteric inhibition of FBPase by AMP.
PMID- 9651343
TI - Nucleosome unfolding during DNA repair in normal and xeroderma pigmentosum (group
C) human cells.
AB - The fate of nucleosomes during nucleotide excision repair is unclear. We have
used organomercurial chromatography to capture accessible thiol groups of
proteins at (or near) nascent repair sites in normal and xeroderma pigmentosum
(group C) human cells. The reactive groups include cysteine 110 of histone H3,
which is exposed in unfolded nucleosomes. Immediately after UV irradiation and a
short pulse labeling of repair patches, intact nuclei were digested with
restriction enzymes to release approximately 18% of the chromatin into soluble
fragments, which are enriched (approximately 4-fold) in a constitutively
transcribed gene. Upon organomercurial affinity fractionation, approximately 1.8%
of the soluble chromatin remains bound in high salt (0.5 M NaCl) and is released
with dithiothreitol. In normal cell chromatin, this fraction is enriched in
nascent repair patches (1.5-1.8-fold) over the unbound fraction. This enrichment
decreases following short chase periods with a time course similar to the loss of
enhanced nuclease sensitivity of these regions (t 1/2 approximately 30 min). Much
less enrichment of nascent repair patches is observed in the thiol-reactive
fraction from XPC cells, which repair primarily the transcribed strand of active
genes. These results suggest that transient nucleosome unfolding occurs during
nucleotide excision repair in normal human cells, and this unfolding may require
the XPC protein.
PMID- 9651344
TI - The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its
transcriptional activity.
AB - The tel gene, recently shown to be translocated in a spectrum of acute and
chronic human leukemias, belongs to the ets family of sequence-specific
transcription factors. To determine the role of Tel in normal hematopoietic
development, we used the tel gene as the bait in the yeast two-hybrid system to
screen a hematopoietic stem cell library. Two partners were identified: Tel binds
to itself, and Tel binds to the ets family member Fli-1. In vitro and in vivo
assays confirmed these interactions. In transient transfection assays, Fli-1
transactivates megakaryocytic specific promoters, and Tel inhibits this effect of
Fli-1. Transactivation studies using deletion mutants of Tel, and the Tel-AML-1
fusion protein, indicate that the helix-loop-helix domain of Tel only partially
inhibits transactivation and that complete inhibition requires the full-length
Tel molecule, including the DNA binding domain. The Tel and Fli-1 proteins are
expressed early in hematopoiesis, and the inability of Tel fusion proteins such
as Tel-AML-1 to counteract Fli-1 mediated transactivation may contribute to the
malignant phenotype in human leukemias where this fusion protein is present.
PMID- 9651345
TI - Human beta-filamin is a new protein that interacts with the cytoplasmic tail of
glycoprotein Ibalpha.
AB - We have cloned and sequenced a 9.4-kilobase cDNA specifying a new 280-kDa protein
interacting with the cytoplasmic tail of glycoprotein (Gp) Ibalpha and showing
considerable homology to actin-binding protein 280 (ABP-280) and chicken retinal
filamin. We term this protein human beta-filamin. The gene for beta-filamin
localizes to chromosome 3p14.3-p21.1. beta-Filamin mRNA expression was observed
in many tissues and in cultured human umbilical vein endothelial cells (HUVECs);
only minimal expression was detected in platelets and the megakaryocytic cell
line CHRF-288. Like ABP-280, beta-filamin contains an NH2-terminal actin-binding
domain, a backbone of 24 tandem repeats, and two "hinge" regions. A polyclonal
antibody to the unique beta-filamin first hinge sequence identifies a strong 280
kDa band in HUVECs but only a weak band in platelets, and stains normal human
endothelial cells in culture and in situ. We have confirmed the interaction of
beta-filamin and GpIbalpha in platelet and HUVEC lysates. In addition, using two
hybrid analysis with deletion mutants, we have localized the binding domain for
GpIbalpha in beta-filamin to residues 1862-2148, an area homologous to the
GpIbalpha binding domain in ABP-280. beta-Filamin is a new member of the filamin
family that may have significance for GpIbalpha function in endothelial cells and
platelets.
PMID- 9651346
TI - Polynucleotide phosphorylase is a component of a novel plant poly(A) polymerase.
AB - We have isolated cDNA clones encoding a novel RNA-binding protein that is a
component of a multisubunit poly(A) polymerase from pea seedlings. The encoded
protein bears a significant resemblance to polynucleotide phosphorylases
(PNPases) from bacteria and chloroplasts. More significantly, this RNA-binding
protein is able to degrade RNAs with the resultant production of nucleotide
diphosphates, and it can add extended polyadenylate tracts to RNAs using ADP as a
donor for adenylate moieties. These activities are characteristic of PNPase.
Antibodies raised against the cloned protein simultaneously immunoprecipitate
both poly(A) polymerase and PNPase activity. We conclude from these studies that
PNPase is the RNA-binding cofactor for this poly(A) polymerase and is an integral
player in the reaction catalyzed by this enzyme. The identification of this RNA
binding protein as PNPase, which is a chloroplast-localized enzyme known to be
involved in mRNA 3'-end determination and turnover (Hayes, R., Kudla, J.,
Schuster, G., Gabay, L., Maliga, P., and Gruissem, W. (1996) EMBO J. 15, 1132
1141), raises interesting questions regarding the subcellular location of the
poly(A) polymerase under study. We have reexamined this issue, and we find that
this enzyme can be detected in chloroplast extracts. The involvement of PNPase in
polyadenylation in vitro provides a biochemical rationale for the link between
chloroplast RNA polyadenylation and RNA turnover which has been noted by others
(Lisitsky, I., Klaff, P., and Schuster, G. (1996) Proc. Natl. Acad. Sci. U. S. A.
93, 13398-13403).
PMID- 9651348
TI - Iron uptake by the halotolerant alga Dunaliella is mediated by a plasma membrane
transferrin.
AB - A 150-kDa transferrin-like protein (Ttf) is associated with the plasma membrane
of the halotolerant unicellular alga Dunaliella salina (Fisher, M., Gokhman, I.,
Pick, U., and Zamir, A. (1997) J. Biol. Chem. 272, 1565-1570). The Ttf level
rises with medium salinity or upon iron depletion. Evidence that Ttf is involved
in iron uptake by Dunaliella is presented here. Algal iron uptake exhibits
characteristics resembling those of animal transferrins: high specificity and
affinity for Fe3+ ions, strict dependence on carbonate/bicarbonate ions, and very
low activity in acidic pH. Reducing the level of Ttf by mild proteolysis of whole
cells is accompanied by lowered uptake activity. Conversely, accumulation of high
levels of Ttf is correlated with an enhancement of iron uptake. Kinetically, iron
uptake consists of two steps: an energy-independent binding of iron to the cell
surface and an energy-dependent internalization. Salinities as high as 3.5 M NaCl
do not inhibit iron uptake or decrease the apparent affinity for Fe3+ ions,
implying that Ttf activity is not affected by high salt. These results indicate
that transferrins, hitherto identified only in animals, are present and function
in iron transport also in plant systems.
PMID- 9651347
TI - Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of
Ca2+ ligands and membrane binding residues.
AB - The C2 domains of conventional protein kinase C (PKC) have been implicated in
their Ca2+-dependent membrane binding. The C2 domain of PKC-alpha contains
several Ca2+ ligands that bind multiple Ca2+ ions and other putative membrane
binding residues. To understand the roles of individual Ca2+ ligands and protein
bound Ca2+ ions in the membrane binding and activation of PKC-alpha, we mutated
five putative Ca2+ ligands (D187N, D193N, D246N, D248N, and D254N) and measured
the effects of mutations on vesicle binding, enzyme activity, and monolayer
penetration of PKC-alpha. Altered properties of these mutants indicate that
individual Ca2+ ions and their ligands have different roles in the membrane
binding and activation of PKC-alpha. The binding of Ca2+ to Asp187, Asp193, and
Asp246 of PKC-alpha is important for the initial binding of protein to membrane
surfaces. On the other hand, the binding of another Ca2+ to Asp187, Asp246,
Asp248, and Asp254 induces the conformational change of PKC-alpha, which in turn
triggers its membrane penetration and activation. Among these Ca2+ ligands,
Asp246 was shown to be most essential for both membrane binding and activation of
PKC-alpha, presumably due to its coordination to multiple Ca2+ ions. Furthermore,
to identify the residues in the C2 domain that are involved in membrane binding
of PKC-alpha, we mutated four putative membrane binding residues (Trp245, Trp247,
Arg249, and Arg252). Membrane binding and enzymatic properties of two double-site
mutants (W245A/W247A and R249A/R252A) indicate that Arg249 and Arg252 are
involved in electrostatic interactions of PKC-alpha with anionic membranes,
whereas Trp245 and Trp247 participate in its penetration into membranes and
resulting hydrophobic interactions. Taken together, these studies provide the
first experimental evidence for the role of C2 domain of conventional PKC as a
membrane docking unit as well as a module that triggers conformational changes to
activate the protein.
PMID- 9651349
TI - Induction of a caspase-3-like activity by calcium in normal cytosolic extracts
triggers nuclear apoptosis in a cell-free system.
AB - Calcium is involved in several steps of the apoptotic process. In nuclei,
endonucleases are presumed to be the main targets of calcium; however, little is
known about its role during the cytosolic phase of apoptosis. We used a cell-free
system to address this question. Our results show that CaCl2 triggered nuclear
apoptosis (i.e. typical morphological change and DNA fragmentation) at
concentrations of 5 mM. This concentration was lowered 10-fold by the co
incubation with cytosolic extracts from nonapoptotic cells. Apoptotic changes
induced by the incubation of nuclei with CaCl2 in the presence of these cytosols
were strongly reduced in the presence of an inhibitor of caspase-3 and to a
lesser extent by an inhibitor of caspase-1. We also show that calcium-induced
apoptosis is affected by protease inhibitors such as N-tosyl-L-phenylalanine
chloromethyl ketone, but not by calpain or several lysosomal protease inhibitors.
The addition of CaCl2 to the cell-free system increased a caspase-3 activity in
nonapoptotic cytosols as shown by specific antibodies and an enzymatic assay. No
activation of a caspase-3-like activity by the addition of cytochrome c was
observed in these extracts under similar conditions. The enhanced caspase-3
activity induced by calcium was inhibited by protease inhibitors affecting
morphological nuclear apoptosis except for those responsible for the degradation
of lamin A. These results suggest that CaCl2 could trigger, in normal cells, an
apoptotic cascade through the activation of cytosolic caspase-3 activity.
PMID- 9651350
TI - Identification of a novel cadherin (vascular endothelial cadherin-2) located at
intercellular junctions in endothelial cells.
AB - Endothelial cells express two major cadherins, VE- and N-cadherins, but only the
former consistently participates in adherens junction organization. In heart
microvascular endothelial cells, we identified a new member of the cadherin
superfamily using polymerase chain reaction. The entire putative coding sequence
was determined. Similarly to protocadherins, while the extracellular domain
presented homology with other members of the cadherin superfamily, the
intracellular region was unrelated either to cadherins or to any other known
protein. We propose for this new protein the name of vascular endothelial
cadherin-2. By Northern blot analysis, the mRNA was present only in cultured
endothelial cell lines but not in other cell types such as NIH 3T3, Chinese
hamster ovary, or L cells. In addition, mRNA was particularly abundant in highly
vascularized organs such as lung or kidney. In endothelial cells and
transfectants, this cadherin was unable to bind catenins and presented a weak
association with the cytoskeleton. This new molecule shares some functional
properties with VE-cadherin and other members of the cadherin family. In Chinese
hamster ovary transfectants it promoted homotypic Ca2+ dependent aggregation and
adhesion and clustered at intercellular junctions. However, in contrast to VE
cadherin, it did not modify paracellular permeability, cell migration, and
density-dependent cell growth. These observations suggest that different
cadherins may promote homophilic cell-to-cell adhesion but that the functional
consequences of this interaction depend on their binding to specific
intracellular signaling/cytoskeletal proteins.
PMID- 9651351
TI - Disruption of vitamin D receptor-retinoid X receptor heterodimer formation
following ras transformation of human keratinocytes.
AB - A partial resistance to the growth inhibitory influence of 1, 25-dihydroxyvitamin
D3 is apparent when immortalized keratinocytes are transformed by the ras
oncogene. The vitamin D receptor (VDR) was isolated, analyzed, and found to be
identical in normal, immortalized, and ras-transformed keratinocytes.
Subsequently, nuclear extracts from immortalized and ras-transformed
keratinocytes were analyzed in gel mobility shift assays utilizing labeled
vitamin D response elements or thyroid hormone response elements. A specific
protein.DNA complex that was shown to contain VDR using an anti-VDR antibody was
identified in both types of extracts; however, the addition of an anti-retinoid X
receptor (RXR) antibody identified RXR in the complex of both normal and
immortalized keratinocyte cell extracts, but not in ras-transformed
keratinocytes. Furthermore, transfection of ras-transformed keratinocytes with
wild-type human RXRalpha rescued VDR.RXR and thyroid hormone receptor.RXR
complexes as demonstrated by a supershift in the presence of the anti-RXR
antibody. Both cell lines were found to express RXRalpha message in equal
amounts. Western blot analysis revealed that RXRalpha protein from ras
transformed keratinocytes was indistinguishable from that from immortalized
keratinocytes and from control cells. These results suggest a causal relationship
between resistance to the growth inhibitory influences of 1,25-dihydroxyvitamin
D3 and disruption of the VDR.RXR complex in malignant keratinocytes.
PMID- 9651352
TI - A mechanism for calmodulin (CaM) trapping by CaM-kinase II defined by a family of
CaM-binding peptides.
AB - Autophosphorylation of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaM
kinase II) induces a striking >1,000-fold increase in its affinity for CaM, which
has been called CaM trapping. Two peptides modeled after the CaM binding domain
of CaM-kinase II were previously shown to kinetically resemble CaM binding to
phosphorylated and dephosphorylated forms of the enzyme, thus providing a model
system with which to define the molecular basis of CaM trapping. In this report,
the specific contribution of each amino acid to the rates of association and
dissociation, and the overall Kd of CaM binding to CaM-kinase II was determined
using an overlapping peptide family, and a fluorescently labeled CaM. The
association rate constants were similar for the entire family of peptides and
ranged from 8 x 10(7) to 32 x 10(7) M-1 s-1. In contrast, the dissociation rate
constants for the peptides varied by >3500-fold and ranged from 0.26 to 7 x 10(
5) s-1. These rate constants yield overall Kd values for binding CaM to the
peptides that range from 2 x 10(-9) M to 2 x 10(-13) M. Extending the low
affinity CaM-binding peptide, CKII(296-312), to include 293Phe-Asn-Ala295
provided the single largest contribution to the decreased dissociation rate
constant, 1,300-fold. It was further shown using Ala-substituted peptides that
the basic residues 296Arg-Arg-Lys299 were also essential for slow CaM
dissociation; however, their contribution was realized only when 293Phe-Asn
Ala295 were present. These results suggest a plausible model in which
autophosphorylation of CaM-kinase II leads to a conformational change in the
region of 293Phe-Asn-Ala295 which makes these residues accessible for binding to
CaM. As a consequence of these changes, further CaM contacts with 296Arg-Arg
Lys299 are established leading to high affinity CaM binding or "CaM trapping."
PMID- 9651353
TI - Differential interactions of the C terminus and the cytoplasmic I-II loop of
neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. I. Molecular
determination.
AB - Interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma)
with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels were investigated using
the Xenopus oocyte expression system. Gi3alpha was found to inhibit both N- and
P/Q-type channels by receptor agonists, whereas Gbeta1 gamma2 was responsible for
prepulse facilitation of N-type channels. L-type channels (alpha1C) were not
regulated by Galpha or Gbeta gamma. For N-type, prepulse facilitation mediated
via Gbeta gamma was impaired when the cytoplasmic I-II loop (loop 1) was deleted
or replaced with the alpha1C loop 1. Galpha-mediated inhibitions were also
impaired by substitution of the alpha1C loop 1, but only when the C terminus was
deleted. For P/Q-type, by contrast, deletion of the C terminus alone diminished
Galpha-mediated inhibition. Moreover, a chimera of L-type with the alpha1B loop 1
gained Gbeta gamma-dependent facilitation, whereas an L-type chimera with the N-
or P/Q-type C terminus gained Galpha-mediated inhibition. These findings provide
evidence that loop 1 of N-type channels is a regulatory site for Gbeta gamma and
the C termini of P/Q- and N-types for Galpha.
PMID- 9651354
TI - Differential interactions of the C terminus and the cytoplasmic I-II loop of
neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. II. Evidence
for direct binding.
AB - The present study was designed to obtain evidence for direct interactions of G
protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B)
and P/Q-type (alpha1A) Ca2+ channels, using synthetic peptides and fusion
proteins derived from loop 1 (cytoplasmic loop between repeat I and II) and the C
terminus of these channels. For N-type, prepulse facilitation as mediated by
Gbeta gamma was impaired when a synthetic loop 1 peptide was applied
intracellularly. Receptor agonist-induced inhibition of N-type as mediated by
Galpha was also impaired by the loop 1 peptide but only when applied in
combination with a C-terminal peptide. For P/Q-type channels, by contrast, the
Galpha-mediated inhibition was diminished by application of a C-terminal peptide
alone. Moreover, in vitro binding analysis for N- and P/Q-type channels revealed
direct interaction of Galpha with C-terminal fusion proteins as well as direct
interaction of Gbeta gamma with loop 1 fusion proteins. These findings define
loop 1 of N- and P/Q-type Ca2+ channels as an interaction site for Gbeta gamma
and the C termini for Galpha.
PMID- 9651355
TI - Crystal structure and mutational analysis of the Escherichia coli putrescine
receptor. Structural basis for substrate specificity.
AB - PotF protein is a periplasmic substrate-binding protein of the putrescine
transport system in Escherichia coli. We have determined the crystal structure of
PotF protein in complex with the substrate at 2.3-A resolution. The PotF molecule
has dimensions of 54 x 42 x 30 A and consists of two similar globular domains.
The PotF structure is reminiscent of other periplasmic receptors with a highest
structural homology to another polyamine-binding protein, PotD. Putrescine is
tightly bound in the deep cleft between the two domains of PotF through 12
hydrogen bonds and 36 van der Waals interactions. The comparison of the PotF
structure with that of PotD provides the insight into the differences in the
specificity between the two proteins. The PotF structure, in combination with the
mutational analysis, revealed the residues crucial for putrescine binding (Trp
37, Ser-85, Glu-185, Trp-244, Asp-247, and Asp-278) and the importance of water
molecules for putrescine recognition.
PMID- 9651356
TI - Adenosine deaminase and A1 adenosine receptors internalize together following
agonist-induced receptor desensitization.
AB - A1 adenosine receptors (A1Rs) and adenosine deaminase (ADA; EC 3.5.4. 4) interact
on the cell surface of DDT1MF-2 smooth muscle cells. The interaction facilitates
ligand binding and signaling via A1R, but it is not known whether it has a role
in homologous desensitization of A1Rs. Here we show that chronic exposure of
DDT1MF-2 cells to the A1R agonist, N6-(R)-(phenylisopropyl)adenosine (R-PIA),
caused a rapid aggregation or clustering of A1 receptor molecules on the cell
membrane, which was enhanced by pretreatment with ADA. Colocalization between A1R
and ADA occurred in the R-PIA-induced clusters. Interestingly, colocalization
between A1R and ADA also occurred in intracellular vesicles after internalization
of both protein molecules in response to R-PIA. Agonist-induced aggregation of
A1Rs was mediated by phosphorylation of A1Rs, which was enhanced and accelerated
in the presence of ADA. Ligand-induced second-messenger desensitization of A1Rs
was also accelerated in the presence of exogenous ADA, and it correlated well
with receptor phosphorylation. However, although phosphorylation of A1R returned
to its basal state within minutes, desensitization continued for hours. The loss
of cell-surface binding sites (sequestration) induced by the agonist was time
dependent (t1/2= 10 +/- 1 h) and was accelerated by ADA. All of these results
strongly suggest that ADA plays a key role in the regulation of A1Rs by
accelerating ligand-induced desensitization and internalization and provide
evidence that the two cell surface proteins internalize via the same endocytic
pathway.
PMID- 9651357
TI - Isolation and characterization of PAGE-1 and GAGE-7. New genes expressed in the
LNCaP prostate cancer progression model that share homology with melanoma
associated antigens.
AB - The LNCaP progression model of human prostate cancer consists of lineage-related
sublines that differ in their androgen sensitivity and metastatic potential. A
differential display polymerase chain reaction was employed to evaluate mRNA
expression differences between the LNCaP sublines in order to define the
differences in gene expression between the androgen-sensitive, nontumorigenic
LNCaP cell line and the androgen-insensitive, metastatic LNCaP sublines, C4-2 and
C4-2B. An amplicon, BG16.21, was isolated that showed increased expression in the
androgen-independent and metastatic LNCaP sublines, C4-2 and C4-2B. Hybridization
screening of a lambda gt11 expression library with BG16.21 revealed two
transcripts, both homologous to BG16.21 at the 3' end. A GenBankTM data base
search using the GCG Wisconsin software package revealed the shorter
approximately 600-bp transcript (designated GAGE-7) to be a new member of the
GAGE family. The second approximately 700-bp transcript was a novel gene
(designated PAGE-1, "prostate associated gene") with only 45% homology to GAGE
gene family members. RNA blot analysis demonstrated that GAGE-7 mRNA was
expressed at equal levels in all lineage related prostate cancer cell sublines,
while PAGE-1 mRNA levels were elevated 5-fold in C4-2 and C4-2B as compared with
LNCaP cells. Neither GAGE-7 nor PAGE-1 demonstrated any regulation by androgens
in the prostate cancer cell lines used in this study. PAGE-1 and GAGE-7
expression was found to be restricted to testes (high) and placenta (low) on
human multiple tissue Northern blots. As GAGE/MAGE antigens were reported
previously to be targets for tumor-specific cytotoxic lymphocytes in melanoma,
these results suggest that PAGE-1 and GAGE-7 may be related to prostate cancer
progression and may serve as potential targets for novel therapies.
PMID- 9651358
TI - Structure-function analysis of FLT3 ligand-FLT3 receptor interactions using a
rapid functional screen.
AB - FLT3 ligand (FLT3L) stimulates primitive hematopoietic cells by binding to and
activating the FLT3 receptor (FLT3R). We carried out a structure-activity study
of human FLT3L in order to define the residues involved in receptor binding. We
developed a rapid method to screen randomly mutagenized FLT3L using a FLT3R-Fc
fusion protein to probe the relative binding activities of mutated ligand.
Approximately 60,000 potential mutants were screened, and the DNA from 59 clones
was sequenced. Thirty-one single amino acid substitutions at 24 positions of
FLT3L either enhanced or reduced activity in receptor binding and cell
proliferation assays. Eleven representative proteins were purified and analyzed
for receptor affinity, specific activity, and physical properties. Receptor
affinity and bioactivity were highly correlated. FLT3L affinity for receptor
improved when four individual mutations that enhance FLT3L receptor affinity were
combined in a single molecule. A model of FLT3L three-dimensional structure was
generated based on sequence alignment and x-ray structure of macrophage colony
stimulating factor. Most residues implicated in receptor binding are widely
dispersed in the primary structure of FLT3L, yet they localize to a surface patch
in the tertiary model. A mutation that maps to and is predicted to disrupt the
proposed dimerization interface between FLT3L monomers exhibits a Stokes radius
that is concentration-dependent, suggesting that this mutation disrupts the FLT3L
dimer.
PMID- 9651359
TI - Mutational analysis of the STAT6 SH2 domain.
AB - The SH2 domain of the STAT family of transcription factors is essential for STAT
binding to phosphorylated cytoplasmic domains of activated cytokine receptors.
Furthermore, the same domain mediates dimerization of activated STAT monomers, a
prerequisite for DNA binding by this family of proteins. To identify amino acid
residues within the STAT protein that mediate these various interactions, we have
carried out an extensive mutational analysis of the Stat6 SH2 domain. Recombinant
proteins carrying C-terminal deletions or double alanine substitutions were
expressed in mammalian and insect cells and assayed for DNA binding,
transcription activation, tyrosine phosphorylation, and the ability to interact
with a tyrosine-phosphorylated peptide derived from the interleukin-4 receptor
signaling chain. From these studies, we have identified amino acids that are
required for both DNA binding and interleukin-4 receptor interaction, as well as
residues that when mutated impair only one of the two functions. Our results
suggest that the structural homology between the SH2 domain of Stat6 and that of
the distantly related Src protein may be higher than predicted on the basis of
primary amino acid sequence comparisons. However, the two types of SH2 domains
may differ at their C-terminal ends.
PMID- 9651360
TI - Merbarone inhibits the catalytic activity of human topoisomerase IIalpha by
blocking DNA cleavage.
AB - Merbarone is a catalytic inhibitor of topoisomerase II that is in clinical trials
as an anticancer agent. Despite the potential therapeutic value of this drug, the
mechanism by which it blocks topoisomerase II activity has not been delineated.
Therefore, to determine the mechanistic basis for the inhibitory action of
merbarone, the effects of this drug on individual steps of the catalytic cycle of
human topoisomerase IIalpha were assessed. Concentrations of merbarone that
inhibited catalytic activity >/=80% had no effect on either enzyme.DNA binding or
ATP hydrolysis. In contrast, the drug was a potent inhibitor of enzyme-mediated
DNA scission (in the absence or presence of ATP), and the inhibitory profiles of
merbarone for DNA cleavage and relaxation were similar. These data indicate that
merbarone acts primarily by blocking topoisomerase II-mediated DNA cleavage.
Merbarone inhibited DNA scission in a global (rather than site-specific) fashion
but did not appear to intercalate into DNA or bind in the minor groove. Since the
drug competed with etoposide (a cleavage-enhancing agent that binds directly to
topoisomerase II), it is proposed that merbarone exerts its inhibitory effects
through interactions with the enzyme and that the drug shares an interaction
domain on topoisomerase II with cleavage-enhancing agents.
PMID- 9651361
TI - Hepatitis C virus core protein interacts with heterogeneous nuclear
ribonucleoprotein K.
AB - Hepatitis C virus (HCV) core protein, a component of viral nucleocapsid, has been
shown to modulate cellular and viral promoter activities. To identify potential
cellular targets for HCV core protein, a human liver cDNA library was screened
for core-interacting proteins using the yeast two-hybrid system. Among the
proteins identified was heterogeneous nuclear ribonucleoprotein K (hnRNP K),
which has been demonstrated to be a transcriptional regulator. The interaction of
HCV core protein with hnRNP K was confirmed by glutathione S-transferase fusion
protein binding assay, protein-protein blotting assay, and coimmunoprecipitation
in vitro and in vivo. Additionally, these two proteins were shown to be partially
colocalized in the nucleus. The hnRNP K-binding site in HCV core protein was
mapped to the region from amino acid residues 25-91, a hydrophilic area near the
N terminus. The HCV core protein-binding domain was located within amino acid
residues 250 to 392, which contain the three proline-rich domains, of hnRNP K.
Furthermore, HCV core protein relieved the suppression effect of hnRNP K on the
activity of the human thymidine kinase gene promoter. The specific binding of HCV
core protein to hnRNP K suggests that multiple functions of hnRNP K may be
disrupted by the core protein during HCV infection and thus explains, in part,
the pathogenesis of HCV.
PMID- 9651362
TI - Platelet-activating factor receptor activation. An initiator step in HIV-1
neuropathogenesis.
AB - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
system results in neuronal apoptosis. Activated HIV-1-infected monocytes secrete
high levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF
alpha) and the phospholipid mediator platelet-activating factor (PAF). TNF-alpha
and PAF are elevated in the central nervous system of patients with HIV-1
associated dementia. We now demonstrate that conditioned media from activated HIV
1-infected monocytes induces neuronal apoptosis, which can be prevented by co
incubation with PAF acetylhydrolase, the enzyme that catabolizes PAF in the
central nervous system. Preceding apoptosis is a TNF-alpha-induced increase in
neuronal ceramide levels. TNF-alpha-mediated neuronal apoptosis can also be
blocked by co-incubation with PAF acetylhydrolase, or a PAF receptor antagonist.
Blocking pathologic activation of PAF receptors may therefore be a pivotal step
in the treatment of HIV-1-associated dementia.
PMID- 9651363
TI - A type I peritrophic matrix protein from the malaria vector Anopheles gambiae
binds to chitin. Cloning, expression, and characterization.
AB - Upon feeding, mosquito midguts secrete the peritrophic matrix (PM), an
extracellular chitin-containing envelope that completely surrounds the blood
meal. Because the malaria parasite must cross the PM to complete its life cycle
in the mosquito, the PM is a potential barrier for malaria transmission. By
antibody screening of an expression library we have identified and partially
characterized a cDNA encoding a putative PM protein, termed Anopheles gambiae
adult peritrophin 1 (Ag-Aper1). Ag-Aper1 is the first cloned PM gene from a
disease vector. Northern analysis detected an abundant Ag-Aper1 transcript only
in the adult gut, and not in any other tissues or at any other stages of
development. The predicted amino acid sequence indicates that it has two tandem
chitin-binding domains that share high sequence similarity with each other and
also with the chitin-binding domain of an adult gut-specific chitinase from the
same organism. The presumed ability of Ag-Aper1 to bind chitin was verified by a
functional assay with the baculovirus-expressed recombinant protein. Ag-Aper1 did
bind to chitin but not to cellulose, indicating that Ag-Aper1 binds chitin
specifically. The double chitin-binding domain organization of Ag-Aper1 suggests
that each protein molecule is able to link two chitin polymer chains. Hence, this
protein is likely to act as a molecular linker that connects PM chitin fibrils
into a three-dimensional network.
PMID- 9651364
TI - Subunit interactions within an expressed regulatory domain of chicken skeletal
myosin. Location of the NH2 terminus of the regulatory light chain by
fluorescence resonance energy transfer.
AB - The regulatory domain (RD), or neck region of the myosin head, consists of two
classes of light chains that stabilize an alpha-helical segment of the heavy
chain. RD from chicken skeletal muscle myosin was prepared in Escherichia coli by
coexpression of a 9-kDa heavy chain fragment with the essential light chain.
Recombinant regulatory light chain (RLC), wild type or mutant, was added
separately to reconstitute the complex. The affinity of RD for divalent cations
was determined by measuring the change in fluorescence of a pair of heavy chain
tryptophans upon addition of calcium or magnesium. The complex bound divalent
cations with high affinity, similar to the association constants determined for
native myosin. The intrinsic fluorescence of the tryptophans could be used as a
donor to measure the fluorescence resonance energy transfer distance to a single
labeled cysteine engineered at position 2 on RLC. Dansylated Cys2 could also
serve as a donor by preparing RLC with a second cysteine at position 79 which was
labeled with an acceptor probe. These fluorescence resonance energy transfer
distances (24-30 A), together with a previous measurement between Cys2 and Cys155
(Wolff-Long, V. L., Tao, T., and Lowey, S. (1995) J. Biol. Chem. 270, 31111
31118) suggest a location for the NH2 terminus of RLC that appears to preclude a
direct interaction between the phosphorylatable serine and specific residues in
the COOH-terminal domain.
PMID- 9651365
TI - Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid
sequences, expression, and regulation.
AB - Pyruvate dehydrogenase phosphatase (PDP) is one of the few mammalian phosphatases
residing within the mitochondrial matrix space. It is responsible for
dephosphorylation and reactivation of the pyruvate dehydrogenase complex (PDC)
and, by this means, is intimately involved in the regulation of utilization of
carbohydrate fuels in mammals. PDP is a dimeric enzyme consisting of catalytic
and regulatory subunits. The catalytic subunit of PDP is a Mg2+-dependent enzyme
homologous to the cytosolic phosphatases of the 2C family. In the present study,
we isolated two cDNAs encoding for mitochondrial phosphatases. The first cDNA is
highly homologous to the previously identified cDNA encoding for the catalytic
subunit of PDP (PDP1). The second cDNA encodes a previously unknown catalytic
subunit of PDP (PDP2). The new phosphatase, expressed as the recombinant protein
in Escherichia coli, shows strict substrate specificity toward PDC and does not
use phosphorylated branched chain alpha-ketoacid dehydrogenase as substrate. Like
PDP1, PDP2 is a Mg2+-dependent enzyme, but its sensitivity to Mg2+ ions is almost
10-fold lower than that of PDP1. In contrast to PDP1, PDP2 is not regulated by
Ca2+ ions. Instead, it is sensitive to the biological polyamine spermine, which,
in turn, has no effect on the enzymatic activity of PDP1. Western blot analysis
of PDP extracted from mitochondria isolated from liver and skeletal muscle
revealed that PDP1 is predominantly expressed in mitochondria from skeletal
muscle, whereas PDP2 is much more abundant in the liver rather than muscle
mitochondria. Both isoenzymes are expressed in mitochondria from 3T3-L1
adipocytes, but the level of expression of PDP2 is considerably higher. These
observations are consistent with previous findings on the enzymatic parameters of
PDP in adipose tissue. Thus, our results provide the first evidence that there
are at least two isoenzymes of PDP in mammals that are different with respect to
tissue distribution and kinetic parameters and, therefore, are likely to be
different functionally.
PMID- 9651366
TI - Molecular cloning, chromosomal localization, tissue distribution, and functional
expression of the human pancreatic sodium bicarbonate cotransporter.
AB - We report the cloning, sequence analysis, tissue distribution, functional
expression, and chromosomal localization of the human pancreatic sodium
bicarbonate cotransport protein (pancreatic NBC (pNBC)). The transporter was
identified by searching the human expressed sequence tag data base. An I.M.A.G.E.
clone W39298 was identified, and a polymerase chain reaction probe was generated
to screen a human pancreas cDNA library. pNBC encodes a 1079-residue polypeptide
that differs at the N terminus from the recently cloned human sodium bicarbonate
cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z.,
Shull, G. E., and Soleimani, M. (1997) J. Biol. Chem. 272, 19111-19114). Northern
blot analysis using a probe specific for the N terminus of pNBC revealed an
approximately 7.7-kilobase transcript expressed predominantly in pancreas, with
less expression in kidney, brain, liver, prostate, colon, stomach, thyroid, and
spinal chord. In contrast, a probe to the unique 5' region of kNBC detected an
approximately 7.6-kilobase transcript only in the kidney. In situ hybridization
studies in pancreas revealed expression in the acini and ductal cells. The gene
was mapped to chromosome 4q21 using fluorescent in situ hybridization. Expression
of pNBC in Xenopus laevis oocytes induced sodium bicarbonate cotransport. These
data demonstrate that pNBC encodes the sodium bicarbonate cotransporter in the
mammalian pancreas. pNBC is also expressed at a lower level in several other
organs, whereas kNBC is expressed uniquely in kidney.
PMID- 9651367
TI - A role for RalGDS and a novel Ras effector in the Ras-mediated inhibition of
skeletal myogenesis.
AB - Oncogenic Ras inhibits the differentiation of skeletal muscle cells through the
activation of multiple downstream signaling pathways, including a Raf-dependent,
mitogen-activated or extracellular signal-regulated kinase kinase/mitogen
activated protein kinase (MEK/MAPK)-independent pathway. Here we report that a
non-Raf binding Ras effector-loop variant (H-Ras G12V,E37G), which retains
interaction with the Ral guanine nucleotide dissociation stimulator (RalGDS),
inhibits the conversion of MyoD-expressing C3H10T1/2 mouse fibroblasts to
skeletal muscle. We show that H-Ras G12V,E37G, RalGDS, and the membrane-localized
RalGDS CAAX protein inhibit the activity of alpha-actin-Luc, a muscle-specific
reporter gene containing a necessary E-box and serum response factor (SRF)
binding site, while a RalGDS protein defective for Ras interaction has no effect
on alpha-actin-Luc transcription. H-Ras G12V,E37G does not activate endogenous
MAPK, but does increase SRF-dependent transcription. Interestingly, RalGDS,
RalGDS CAAX, and RalA G23V inhibit H-Ras G12V, E37G-induced expression of an SRF
regulated reporter gene, demonstrating that signaling through RalGDS does not
duplicate the action of H-Ras G12V,E37G in this system. As additional evidence
for this, we show that H-Ras G12V,E37G inhibits the expression of troponin I-Luc,
an SRF-independent muscle-specific reporter gene, whereas RalGDS and RalGDS CAAX
do not. Although our studies show that signaling through RalGDS can interfere
with the expression of reporter genes dependent on SRF activity (including alpha
actin-Luc), our studies also provide strong evidence that an additional signaling
molecule(s) activated by H-Ras G12V,E37G is required to achieve the complete
inhibition of the myogenic differentiation program.
PMID- 9651368
TI - A hinge at the central helix of the regulatory light chain of myosin is critical
for phosphorylation-dependent regulation of smooth muscle myosin motor activity.
AB - The motor function of smooth muscle myosin is activated by phosphorylation of the
regulatory light chain (RLC) at Ser19. However, the molecular mechanism by which
the phosphorylation activates the motor function is not yet understood. In the
present study, we focused our attention on the role of the central helix of RLC
for regulation. The flexible region at the middle of the central helix (Gly95
Pro98) was substituted or deleted to various extents, and the effects of the
deletion or substitution on the regulation of the motor activity of myosin were
examined. Deletion of Gly95-Asp97, Gly95-Thr96, or Thr96-Asp97 decreased the
actin-translocating activity of myosin a little, but the phosphorylation
dependent regulation of the motor activity was not disrupted. In contrast, the
deletion of Gly95-Pro98 of RLC completely abolished the actin translocating
activity of phosphorylated myosin. However, the unregulated myosin long
subfragment 1 containing this RLC mutant showed motor activity the same as that
containing the wild type RLC. Since long subfragment 1 motor activity is
unregulated by phosphorylation, i.e. constitutively active, these results suggest
that the deletion of these residues at the central helix of RLC disrupts the
phosphorylation-mediated activation mechanism but not the motor function of
myosin itself. On the other hand, the elimination of Pro98 or substitution of
Gly95-Pro98 by Ala resulted in the activation of actin translocating activity of
dephosphorylated myosin, whereas it did not affect the motor activity of
phosphorylated myosin. Together, these results clearly indicate the importance of
the hinge at the central helix of RLC on the phosphorylation-mediated regulation
of smooth muscle myosin.
PMID- 9651369
TI - The death inhibitory molecules CED-9 and CED-4L use a common mechanism to inhibit
the CED-3 death protease.
AB - The apoptotic machinery of Caenorhabditis elegans includes three core interacting
components: CED-3, CED-4, and CED-9. CED-3 is a death protease composed of a
prodomain and a protease domain. CED-4 is a P-loop-containing, nucleotide-binding
molecule that complexes with the single polypeptide zymogen form of CED-3,
promoting its activation by autoprocessing. CED-9 blocks death by complexing with
CED-4 and suppressing its ability to promote CED-3 activation. A naturally
occurring alternatively spliced form of CED-4 that contains an insertion within
the nucleotide-binding region (CED-4L) functions as a dominant negative inhibitor
of CED-3 processing and attenuates cell death. Domain mapping studies revealed
that distinct regions within CED-4 bind to the CED-3 prodomain and protease
domain. Importantly, the CED-4 P-loop was involved in prodomain binding.
Disruption of P-loop geometry because of mutation of a critical lysine (K165R) or
insertional inactivation (CED-4L) abolished prodomain binding. Regardless, K165R
and CED-4L still retained CED-3 binding through the protease domain but were
unable to initiate CED-3 processing. Therefore, the P-loop-prodomain interaction
is critical for triggering CED-4-mediated CED-3 processing. Underscoring the
importance of this interaction was the finding that CED-9 contacted the P-loop
and selectively inhibited its interaction with the CED-3 prodomain. These results
provide a simple mechanism for how CED-9 functions to block CED-4-mediated CED-3
processing and cell death.
PMID- 9651370
TI - Interaction of eye protein kinase C and INAD in Drosophila. Localization of
binding domains and electrophysiological characterization of a loss of
association in transgenic flies.
AB - Drosophila eye-specific protein kinase C (eye-PKC) is involved in light
adaptation and deactivation. eye-PKC, NORPA (phospholipase Cbeta), and transient
receptor-potential (TRP) (calcium channel) are integral components of a signal
transduction complex organized by INAD, a protein containing five PDZ domains. We
previously demonstrated the direct association between the third PDZ domain of
INAD with TRP in addition to the carboxyl-terminal half of INAD with the last
three residues of NORPA. In this work, the molecular interaction between eye-PKC
and INAD is defined via the yeast two-hybrid and ligand overlay assays. We show
that the second PDZ domain of INAD interacts with the last three residues in the
carboxyl-terminal tail of eye-PKC, Thr-Ile-Ile. The association between eye-PKC
and INAD is disrupted by an amino acid substitution (Ile-700 to Asp) at the final
residue of eye-PKC. In flies lacking endogenous eye-PKC (inaCp215), normal visual
physiology is restored upon expression of wild-type eye-PKC, whereas the eye
PKCI700D mutant is completely inactive. Flies homozygous for inaCp209 and
InaDp215, a mutation that causes a loss of the INAD-TRP association, were
generated. These double mutants display a more severe response inactivation than
either of the single mutants. Based on these findings, we conclude that the in
vivo activity of eye-PKC depends on its association with INAD and that the
sensitivity of photoreceptors is cooperatively regulated by the presence of both
eye-PKC and TRP in the signaling complex.
PMID- 9651371
TI - Inhibition of hGrb10 binding to the insulin receptor by functional domain
mediated oligomerization.
AB - hGrb10 is a newly identified Src homology 2 (SH2) and pleckstrin homology (PH)
domain-containing protein that binds to autophosphorylated receptor tyrosine
kinases, including the insulin and insulin-like growth factor receptors. To
identify potential downstream proteins that interact with hGrb10, we screened a
yeast two-hybrid cDNA library using the full-length hGrb10gamma as bait. A
fragment of hGrb10, which included the IPS (insert between the PH and SH2 domain)
and the SH2 domains, was found to bind with high affinity to the full-length
protein. The interaction between the IPS/SH2 domain and the full-length hGrb10
was further confirmed by in vitro glutathione S-transferase fusion protein
binding studies. Gel filtration assays showed that hGrb10 underwent
tetramerization in mammalian cells. The interaction involved at least two
functional domains, the IPS/SH2 region and the PH domain, both of which
interacted with the NH2-terminal amino acid sequence of hGrb10gamma (hGrb10gamma
DeltaC, residues 4-414). Competition studies showed that hGrb10gamma DeltaC
inhibited the binding of hGrb10 to the tyrosine-phosphorylated insulin receptor,
suggesting that this region may play a regulatory role in hGrb10/insulin receptor
interaction. We present a model for hGrb10 tetramerization and its potential role
in receptor tyrosine kinase signal transduction.
PMID- 9651372
TI - Acylamino acid-releasing enzyme from the thermophilic archaeon Pyrococcus
horikoshii.
AB - When the genome of the thermophilic archaeon Pyrococcus horikoshii was sequenced,
a gene homologous to the mammalian gene for an acylamino acid-releasing enzyme
(EC 3.4.19.1) was found in which the enzyme's proposed active residues were
conserved. The P. horikoshii gene comprised an open reading frame of 1,896 base
pairs with an ATG initiation codon and a TAG termination codon, encoding a 72,390
Da protein of 632 amino acid residues. This gene was overexpressed in Escherichia
coli with the pET vector system, and the resulting enzyme showed the anticipated
amino-terminal sequence and high hydrolytic activity for acylpeptides. This
enzyme was concluded to be the first acylamino acid-releasing enzyme from an
organism other than a eukaryotic cell. The existence of the enzyme in archaea
suggests that the mechanisms of protein degradation or initiation of protein
synthesis or both in archaea may be similar to those in eukaryotes. The enzyme
was stable at 90 degreesC, with its optimum temperature over 90 degreesC. The
specific activity of the enzyme increased 7-14-fold with heat treatment,
suggesting the modification of the enzyme's structure for optimal hydrolytic
activity by heating. This enzyme is expected to be useful for the removal of
Nalpha-acylated residues in short peptide sequence analysis at high temperatures.
PMID- 9651373
TI - SNAP-23 requirement for transferrin recycling in Streptolysin-O-permeabilized
Madin-Darby canine kidney cells.
AB - Fusion of recycling and transcytotic vesicles with the apical and basolateral
plasma membrane domains of Madin-Darby canine kidney (MDCK) cells requires the N
ethylmaleimide-sensitive factor and is sensitive to botulinum neurotoxin serotype
E (BoNT/E). BoNT/E is thought to selectively proteolyze the 25,000-dalton
synaptosomal associated protein (SNAP-25), a protein found in neurons or cells of
neuroendocrine origin. However, SNAP-25 is not found in MDCK cells. One possible
target for BoNT/E in MDCK cells is SNAP-23, a newly described SNAP-25 homolog
that is found in several organs including kidney. Currently, the function of SNAP
23 is unknown. We have reconstituted transferrin recycling in permeabilized MDCK
cells to assess the role of SNAP-23 in the endocytic traffic of this protein. We
find that: (i) SNAP-23 is expressed in MDCK cells and is found both at the
basolateral plasma membrane and associated with apical and basolateral vesicles,
(ii) canine SNAP-23 is cleaved by BoNT/E, (iii) transferrin recycling is N
ethylmaleimide-sensitive factor-dependent and BoNT/E-sensitive, and (iv) addition
of either exogenous SNAP-23 or anti-SNAP-23 antibodies inhibits ligand recycling.
Our observations suggest that SNAP-23 may be required for fusion of recycling
vesicles with the basolateral membrane of polarized MDCK cells.
PMID- 9651374
TI - Role of tyrosine kinases in induction of the c-jun proto-oncogene in irradiated B
lineage lymphoid cells.
AB - Exposure of B-lineage lymphoid cells to ionizing radiation induces an elevation
of c-jun proto-oncogene mRNA levels. This signal is abrogated by protein-tyrosine
kinase (PTK) inhibitors, indicating that activation of an as yet unidentified PTK
is mandatory for radiation-induced c-jun expression. Here, we provide
experimental evidence that the cytoplasmic tyrosine kinases BTK, SYK, and LYN are
not required for this signal. Lymphoma B-cells rendered deficient for LYN, SYK,
or both by targeted gene disruption showed increased c-jun expression levels
after radiation exposure, but the magnitude of the stimulation was lower than in
wild-type cells. Thus, these PTKs may participate in the generation of an optimal
signal. Notably, an inhibitor of JAK-3 (Janus family kinase-3) abrogated
radiation-induced c-jun activation, prompting the hypothesis that a chicken
homologue of JAK-3 may play a key role in initiation of the radiation-induced c
jun signal in B-lineage lymphoid cells.
PMID- 9651375
TI - GTPase activating specificity of RGS12 and binding specificity of an
alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain.
AB - Regulator of G-protein signaling (RGS) proteins increase the intrinsic guanosine
triphosphatase (GTPase) activity of G-protein alpha subunits in vitro, but how
specific G-protein-coupled receptor systems are targeted for down-regulation by
RGS proteins remains uncharacterized. Here, we describe the GTPase specificity of
RGS12 and identify four alternatively spliced forms of human RGS12 mRNA. Two
RGS12 isoforms of 6.3 and 5.7 kilobases (kb), encoding both an N-terminal PDZ
(PSD-95/Dlg/ZO-1) domain and the RGS domain, are expressed in most tissues, with
highest levels observed in testis, ovary, spleen, cerebellum, and caudate
nucleus. The 5.7-kb isoform has an alternative 3' end encoding a putative C
terminal PDZ domain docking site. Two smaller isoforms, of 3.1 and 3.7 kb, which
lack the PDZ domain and encode the RGS domain with and without the alternative 3'
end, respectively, are most abundantly expressed in brain, kidney, thymus, and
prostate. In vitro biochemical assays indicate that RGS12 is a GTPase-activating
protein for Gi class alpha subunits. Biochemical and interaction trap experiments
suggest that the RGS12 N terminus acts as a classical PDZ domain, binding
selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the
interleukin-8 receptor B (CXCR2) and the alternative 3' exon form of RGS12. The
presence of an alternatively spliced PDZ domain within RGS12 suggests a mechanism
by which RGS proteins may target specific G-protein-coupled receptor systems for
desensitization.
PMID- 9651376
TI - Cloning and characterization of a novel binding factor (GMEB-2) of the
glucocorticoid modulatory element.
AB - The 21-base pair glucocorticoid modulatory element (GME) of the rat tyrosine
aminotransferase gene is the only cis-acting element known to modulate the
transcriptional activity of receptors bound to glucocorticoid response elements.
Specifically, the GME increases the activity of complexes bound both by
physiological concentrations of glucocorticoids, due to a left shift in the dose
response curve, and by saturating concentrations of anti-glucocorticoids. For
this reason, the nuclear protein(s) that has been demonstrated to bind to the GME
is of major interest as a possible transcription factor with hitherto undescribed
properties. Subsequent studies indicated that not one but two proteins of 88 and
67 kDa (= GMEB-1 and -2, respectively) formed a heteromeric complex with double
stranded GME oligonucleotides in gel shift assays and participated in the
expression of GME activity (Oshima, H., Szapary, D., and Simons, S. S., Jr.
(1995) J. Biol. Chem. 270, 21893-21910). Here, we report the use of polymerase
chain reaction of degenerate oligonucleotides and 5'- and 3'-rapid amplification
of cDNA ends to clone two cDNAs of 2. 0 and 1.9 kilobase pairs that probably
result from alternative splicing. Both cDNAs encoded open reading frames
containing all four previously sequenced peptides. The longer 2.0-kilobase pair
cDNA encoded an open reading frame for an acidic, 529-amino acid protein and
afforded a major 67-kDa and a minor 58-kDa protein after in vitro
transcription/translation. Both proteins were recognized by a mono-epitopic
antibody raised against a peptide of GMEB-2. The in vitro translated protein
bound to GME DNA in gel shift assays. However, the binding to GME DNA increased
markedly after mixing with authentic GMEB-1 to give a gel-shifted complex that
was similar to that derived from HTC cell cytosol. GMEB-2 shares a unique domain
(KDWKR) with proteins derived from diverse organisms as follows: Drosophila (DEAF
I), rat (Suppressin), and Caenorhabditis elegans (three unknown open reading
frames). Collectively, these data suggest that the 67-kDa GMEB-2 not only is an
important factor for the modulation of glucocorticoid receptor bound to
glucocorticoid response elements but also may belong to a novel family of
transcription factors.
PMID- 9651377
TI - Ceramides are bound to structural proteins of the human foreskin epidermal
cornified cell envelope.
AB - An important component of barrier function in human epidermis is contributed by
ceramides that are bound by ester linkages to undefined proteins of the cornified
cell envelope (CE). In this paper, we have examined the protein targets for the
ceramide attachment. By partial saponification of isolated foreskin epidermal CEs
followed by limited proteolysis, we have recovered several lipopeptides.
Biochemical and mass spectroscopic characterization revealed that all contained
near stoichiometric amounts of ceramides of masses ranging from about 690 to 890
atomic mass units, of which six quantitatively major species were common. The
array of ceramides was similar to that obtained from pig skin, the composition of
which is known, thereby providing strong indirect data for their fatty acid and
sphingosine compositions. The recovered peptides accounted for about 20% of the
total foreskin CE ceramides. By amino acid sequencing, about 35% of the peptides
were derived from ancestral glutamine-glutamate-rich regions of involucrin, an
important CE structural protein. Another 18% derived from rod domain sequences of
periplakin and envoplakin, which are also known or suspected CE proteins. Other
peptides were too short for unequivocal identification. Together, these data
indicate that involucrin, envoplakin, periplakin, and possibly other structural
proteins serve as substrates for the attachment of ceramides by ester linkages to
the CE for barrier function in human epidermis.
PMID- 9651378
TI - Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is
glucose-dependent. Synergistic activation of insulin receptor substrate-mediated
signal transduction pathways by glucose and IGF-I in INS-1 cells.
AB - Nutrients and certain growth factors stimulate pancreatic beta-cell mitogenesis,
however, the appropriate mitogenic signal transduction pathways have not been
defined. In the glucose-sensitive pancreatic beta-cell line, INS-1, it was found
that glucose (6-18 mM) independently increased INS-1 cell proliferation (>20-fold
at 15 mM glucose). Insulin-like growth factor I (IGF-I)-induced INS-1 cell
proliferation was glucose-dependent only in the physiologically relevant
concentration range (6-18 mM glucose). The combination of IGF-I and glucose was
synergistic, increasing INS-1 cell proliferation >50-fold at 15 mM glucose + 10
nM IGF-I. Glucose metabolism and phosphatidylinositol 3'-kinase (PI 3'-kinase)
activation were necessary for both glucose and IGF-I-stimulated INS-1 cell
proliferation. IGF-I and 15 mM glucose increased tyrosine phosphorylation
mediated recruitment of Grb2/mSOS and PI 3'-kinase to IRS-2 and pp60. Glucose and
IGF-I also induced Shc association with Grb2/mSOS. Glucose (3-18 mM) and IGF-I,
independently of glucose, activated mitogen-activated protein kinase but this did
not correlate with IGF-I-induced beta-cell proliferation. In contrast, p70(S6K)
was activated with increasing glucose concentration (between 6 and 18 mM), and
potentiated by IGF-I in the same glucose concentration range which correlated
with INS-1 cell proliferation rate. Thus, glucose and IGF-I-induced beta-cell
proliferation were mediated via a signaling mechanism that was facilitated by
mitogen-activated protein kinase but dependent on IRS-mediated induction of PI 3'
kinase activity and downstream activation of p70(S6K). The glucose dependence of
IGF-I mediated INS-1 cell proliferation emphasizes beta-cell signaling mechanisms
are rather unique in being tightly linked to glycolytic metabolic flux.
PMID- 9651379
TI - Expression and characterization of a 70-kDa fragment of the insulin receptor that
binds insulin. Minimizing ligand binding domain of the insulin receptor.
AB - In order to characterize regions of the insulin receptor that are essential for
ligand binding and possibly identify a smaller insulin-binding fragment of the
receptor, we have used site-directed mutagenesis to construct a series of insulin
receptor deletion mutants. From 112 to 246 amino acids were deleted from the
alpha-subunit region comprising amino acids 469-729. The receptor constructs were
expressed as soluble insulin receptor IgG fusion proteins in baby hamster kidney
cells and were characterized in binding assays by immunoblotting and chemical
cross-linking with radiolabeled insulin. The shortest receptor fragment
identified was a free monomeric alpha-subunit deleted of amino acids 469-703 and
718-729 (exon 11); the mass of this receptor fragment was found by mass
spectrometry to be 70 kDa. This small insulin receptor fragment bound insulin
with an affinity (Kd) of 4.4 nM, which is similar to what was found for the full
length ectodomain of the insulin receptor (5.0 nM). Cross-linking experiments
confirmed that the 70-kDa receptor fragment specifically bound insulin. In
summary we have minimized the insulin binding domain of the insulin receptor by
identifying a 70-kDa fragment of the ectodomain that retains insulin binding
affinity making this an interesting candidate for detailed structural analysis.
PMID- 9651380
TI - Adrenomedullin gene expression is developmentally regulated and induced by
hypoxia in rat ventricular cardiac myocytes.
AB - Adrenomedullin is a recently discovered hypotensive peptide that is expressed in
a variety of cell and tissue types. Using the technique of differential display,
the adrenomedullin gene was observed to be differentially expressed in developing
rat heart. Reverse transcription-polymerase chain reaction analysis revealed that
the level of adrenomedullin mRNA was significantly higher in adult ventricular
cardiac muscle as compared with embryonic day 17 ventricular cardiac muscle.
Adrenomedullin receptor mRNA was constitutively expressed throughout development
of the ventricular heart. Two potential hypoxia-inducible factor-1 (HIF-1)
consensus binding sites were identified in the mouse adrenomedullin promoter at
1095 and -770 nucleotides from the transcription start site. Exposure of cultured
adult rat ventricular cardiac myocytes to hypoxia (1% O2) resulted in a
significant, time-dependent increase in adrenomedullin mRNA levels. Transfection
studies revealed that the 5'-flanking sequence of adrenomedullin was capable of
mediating a hypoxia-inducible increase in transcription. Mutation of the putative
HIF-1 consensus binding sites revealed that the major regulatory sequence that
mediates the hypoxia-inducible transcriptional response is located at -1095.
These data demonstrate that the adrenomedullin gene is developmentally regulated
in ventricular cardiomyocytes, that adrenomedullin transcription can be induced
by hypoxia, and that this response is primarily mediated by HIF-1 consensus sites
in the adrenomedullin promoter.
PMID- 9651381
TI - Apolipoprotein(a) synthesis and secretion from hepatoma cells is coupled to
triglyceride synthesis and secretion.
AB - Apolipoprotein(a) (apo(a)) is synthesized and secreted from liver cells and
represents one of the two major protein components of the atherogenic
lipoprotein, Lp(a). Little is known, however, of the factors that regulate the
secretion of this protein. We have undertaken an analysis of the response to
oleate supplementation in stable clones of HepG2 and McA-RH7777 cells expressing
either a 6 K-IV or 17 K-IV isoform of apo(a). These cell lines were examined by
pulse-chase analysis and each demonstrated an increase (range 2-6-fold) in apo(a)
secretion following supplementation with 0.8 mM oleate. Microsomal membranes,
prepared from HepG2 cells expressing a 6 K-IV apo(a) isoform, demonstrated that
oleate supplementation increased the apparent protection of apo(a) from protease
digestion, suggesting that alterations in the translocation efficiency of apo(a)
may accompany the addition of oleate. Cells incubated with brefeldin A
demonstrated increased recovery of the precursor form of apo(a) with oleate
supplementation, suggesting that alterations in post-translational degradation
may also contribute to the observed increase in apo(a) secretion following oleate
addition. To further characterize the oleate-dependent increase in apo(a)
secretion, cells were incubated with an inhibitor of the microsomal triglyceride
transfer protein. These experiments demonstrated a dose-dependent decrease in
apo(a) secretion from both cell lines. Furthermore, addition of either the
microsomal triglyceride transfer protein inhibitor or triacsin C, an inhibitor of
acyl-CoA synthase, completely abrogated the oleate-dependent increase in apo(a)
secretion. Taken together, these data provide evidence that apo(a) secretion from
hepatoma cells may be linked to elements of cellular triglyceride assembly and
secretion.
PMID- 9651382
TI - Second-site cleavage in sterol regulatory element-binding protein occurs at
transmembrane junction as determined by cysteine panning.
AB - In response to sterol deprivation, two sequential proteolytic cleavages release
the NH2-terminal fragments of sterol regulatory element-binding proteins (SREBPs)
from cell membranes. The fragments translocate to the nucleus where they activate
genes involved in cholesterol and fatty acid metabolism. The SREBPs are bound to
membranes in a hairpin fashion. The NH2-terminal and COOH-terminal domains face
the cytoplasm, separated by two membrane spanning segments and a short lumenal
loop. The first cleavage occurs at Site-1 in the lumenal loop. The NH2-terminal
fragment is then released by cleavage at Site-2, which is believed to lie within
the first transmembrane segment. Here, we use a novel cysteine panning method to
identify the second cleavage site (Site-2) in human SREBP-2 as the Leu484-Cys485
bond that lies at the junction between the cytoplasmic NH2-terminal fragment and
the first transmembrane segment. We transfected cells with cDNAs encoding fusion
proteins with single cysteine residues at positions to the NH2-terminal and COOH
terminal sides of cysteine 485. The NH2-terminal fragments were tested for
susceptibility to modification with Nalpha-(3-maleimidylpropionyl)biocytin, which
attaches a biotin group to cysteine sulfhydryls. Cysteines to the NH2-terminal
side of cysteine 485 were retained on the NH2-terminal fragment, but cysteines to
the COOH-terminal side of leucine 484 were lost. Leucine 484 is three residues to
the COOH-terminal side of the tetrapeptide Asp-Arg-Ser-Arg, which immediately
precedes the first transmembrane segment and is required for Site-2 cleavage.
PMID- 9651383
TI - Transactivation of the human apolipoprotein CII promoter by orphan and ligand
dependent nuclear receptors. The regulatory element CIIC is a thyroid hormone
response element.
AB - The regulatory elements CIIC (-159/-116) and CIIB (-102/-81) of the
apolipoprotein CII (apoCII) promoter have distinct specificities for orphan
nuclear receptors (Vorgia, P., Zannis, V. I., and Kardassis, D. (1998) J. Biol.
Chem. 273, 4188-4199). In this communication we investigated the contribution of
ligand-dependent and orphan nuclear receptors on the transcriptional regulation
of the human apoCII gene. It was found that element CIIC in addition to ARP-1 and
EAR-2 binds RXRalpha/T3Rbeta heterodimers strongly, whereas element CIIB binds
hepatic nuclear factor 4 (HNF-4) exclusively. Binding is abolished by mutations
that alter the HRE binding motifs. Transient cotransfection experiments showed
that in the presence of T3, RXRalpha/T3Rbeta heterodimers transactivated the
205/+18 apoCII promoter 1.6- and 11-fold in HepG2 and COS-1 respectively. No
transactivation was observed in the presence of 9-cis-retinoic acid.
Transactivation requires the regulatory element CIIC, suggesting that this
element contains a thyroid hormone response element. HNF-4 did not affect the
apoCII promoter activity in HepG2 cells. However, mutations in the HNF-4 binding
site on element CIIB and inhibition of HNF-4 synthesis in HepG2 cells by
antisense HNF-4 constructs decreased the apoCII promoter activity to 25-40% of
the control, indicating that HNF-4 is a positive regulator of the apoCII gene.
ARP-1 repressed the -205/+18 but not the -104/+18 apoCII promoter activity in
HepG2 cells, indicating that the repression depends on the regulatory element
CIIC. In contrast, combination of ARP-1 and HNF-4 transactivated different apoCII
promoter segments as well as a minimal adenovirus major late promoter driven by
the regulatory element CIIB. Mutagenesis or deletion of elements CIIB or CIIC
established that the observed transactivation requires DNA binding of one of the
two factors and may result from HNF-4-ARP-1 interactions that elicit the
transactivation functions of HNF-4. The combined data indicate that
RXRalpha/T3Rbeta in the presence of T3 and HNF-4 can upregulate the apoCII
promoter activity by binding to the regulatory elements CIIC and CIIB,
respectively. In addition, ARP-1 can either have inhibitory or stimulatory
effects on the apoCII promoter activity via different mechanisms.
PMID- 9651384
TI - Lipid products of phosphoinositide 3-kinase and phosphatidylinositol 4',5'
bisphosphate are both required for ADP-dependent platelet spreading.
AB - We have shown previously that ADP released upon platelet adhesion mediated by
alphaIIb beta3 integrin triggers accumulation of phosphatidylinositol 3',4'
bisphosphate (PtdIns-3,4-P2) (Gironcel, D. , Racaud-Sultan, C., Payrastre, B.,
Haricot, M., Borchert, G., Kieffer, N., Breton, M., and Chap, H. (1996) FEBS
Lett. 389, 253-256). ADP has also been involved in platelet spreading. Therefore,
in order to study a possible role of phosphoinositide 3-kinase in platelet
morphological changes following adhesion, human platelets were pretreated with
specific phosphoinositide 3-kinase inhibitors LY294002 and wortmannin. Under
conditions where PtdIns-3, 4-P2 synthesis was totally inhibited (25 microM
LY294002 or 100 nM wortmannin), platelets adhered to the fibrinogen matrix,
extended pseudopodia, but did not spread. Moreover, addition of ADP to the medium
did not reverse the inhibitory effects of phosphoinositide 3-kinase inhibitors on
platelet spreading. Although synthetic dipalmitoyl PtdIns-3,4-P2 and dipalmitoyl
phosphatidylinositol 3',4', 5'-trisphosphate restored only partially platelet
spreading, phosphatidylinositol 4',5'-bisphosphate (PtdIns-4,5-P2) was able to
trigger full spreading of wortmannin-treated adherent platelets. Following 32P
labeling of intact platelets, the recovery of [32P]PtdIns-4,5-P2 in anti-talin
immunoprecipitates from adherent platelets was found to be decreased upon
treatment by wortmannin. These results suggest that the lipid products of
phosphoinositide 3-kinase are required but not sufficient for ADP-induced
spreading of adherent platelets and that PtdIns-4,5-P2 could be a downstream
messenger of this signaling pathway.
PMID- 9651385
TI - Complete exon-intron organization of the human gene for the alpha1 chain of type
XV collagen (COL15A1) and comparison with the homologous COL18A1 gene.
AB - The human gene for the alpha1 chain of type XV collagen (COL15A1) is about 145
kilobases in size and contains 42 exons. The promoter is characterized by the
lack of a TATAA motif and the presence of several Sp1 binding sites, some of
which appeared to be functional in transfected HeLa cells. Comparison with
Col18a1, which encodes the alpha1(XVIII) collagen chain homologous with
alpha1(XV), indicates marked structural homology spread throughout the two genes.
The mouse Col18a1 contains one exon more than COL15A1, due to the fact that
COL15A1 lacks sequences corresponding to exon 3 of Col18a1, which encodes a
cysteine-rich sequence motif. Twenty-five of the exons of the two genes are
almost identical in size, six of them contain conserved split codons, and the
locations of the respective exon-intron junctions are identical or almost
identical in the two genes. The homologous exons include the closely adjacent
first pair of exons and the exons encoding a thrombospondin-1 homology found in
the N-terminal noncollagenous domain 1, which are followed by the most variable
part of the two genes, covering the C-terminal half of their noncollagenous
domain 1 and the beginning of the collagenous portion, after which most of the
exons are homologous. The lengths of the introns are not similar in these genes,
with two exceptions, namely the first intron, which is very short, less than 100
base pairs, and the second intron, which is very large, about 50 kilobases, in
both genes. It can be concluded that COL15A1 and Col18a1 are derived from a
common ancestor.
PMID- 9651386
TI - Differential expression of agrin in renal basement membranes as revealed by
domain-specific antibodies.
AB - We determined the specificity of two hamster monoclonal antibodies and a sheep
polyclonal antiserum against heparan sulfate proteoglycan isolated from rat
glomerular basement membrane. The antibodies were characterized by enzyme-linked
immunosorbent assay on various basement membrane components and
immunoprecipitation with heparan sulfate proteoglycan with or without
heparitinase pre-treatment. These experiments showed that the antibodies
specifically recognize approximately 150-, 105-, and 70-kDa core proteins of rat
glomerular basement membrane heparan sulfate proteoglycan. Recently, we showed
that agrin is a major heparan sulfate proteoglycan in the glomerular basement
membrane (Groffen, A. J. A., Ruegg, M. A., Dijkman, H. B. P. M., Van der Velden,
T. J., Buskens, C. A., van den Born, J., Assmann, K. J. M., Monnens, L. A. H.,
Veerkamp, J. H., and van den Heuvel, L. P. W. J. (1998) J. Histochem. Cytochem.
46, 19-27). Therefore, we tested whether our antibodies recognize agrin. To this
end, we evaluated staining of Chinese hamster ovary cells transfected with
constructs encoding full-length or the C-terminal half of rat agrin by analysis
on a fluorescence-activated cell sorter. Both hamster monoclonals and the sheep
antiserum clearly stained cells transfected with the construct encoding full
length agrin, whereas wild type cells and cells transfected with the construct
encoding the C-terminal part of agrin were not recognized. A panel of previously
characterized monoclonals, directed against C-terminal agrin, clearly stained
cells transfected with either of the constructs but not wild type cells. This
indicates that both hamster monoclonals and the sheep antiserum recognize
epitopes on the N-terminal half of agrin. By immunohistochemistry on rat renal
tissue, we compared distribution of N-terminal agrin with that of C-terminal
agrin. The monoclonal antibodies against C-terminal agrin stained almost
exclusively the glomerular basement membrane, whereas the anti-N-terminal agrin
antibodies recognized all renal basement membranes, including tubular basement
membranes. Based on these results, we hypothesize that full-length agrin is
predominantly expressed in the glomerular basement membrane, whereas in most
other renal basement membranes a truncated isoform of agrin is predominantly
found that misses (part of) the C terminus, which might be due to alternative
splicing and/or posttranslational processing. The possible significance of this
finding is discussed.
PMID- 9651387
TI - Characterization of recombinant CD45 cytoplasmic domain proteins. Evidence for
intramolecular and intermolecular interactions.
AB - CD45 is a transmembrane two-domain tyrosine phosphatase required for efficient
signal transduction initiated by lymphocyte antigen receptors. As with most
transmembrane two-domain phosphatases, the role of the second phosphatase domain
is unclear. In this study, recombinant CD45 cytoplasmic domain proteins purified
from bacteria were used to evaluate the function of the individual phosphatase
domains. A recombinant protein expressing the membrane-proximal region, first
phosphatase domain, and spacer region of CD45 (rD1) was catalytically active and
found to exist primarily as a dimer. In contrast to this, a recombinant protein
expressing the spacer region, the second phosphatase domain and the carboxy tail
of CD45 (rD2) existed as a monomer and had no catalytic activity against any of
the substrates tested. Comparison of rD1 with the recombinant protein expressing
the entire cytoplasmic domain of CD45 (rD1/D2) indicated that rD1/D2 was 2-3-fold
more catalytically active, was more thermostable, and existed primarily as a
monomer. Limited trypsin digestion of rD1/D2 provided evidence for a noncovalent
association between an N-terminal 27-kDa fragment and a C-terminal 53-kDa
fragment, suggesting an intramolecular interaction. Furthermore, rD1 was found to
specifically associate with rD2 in an in vitro binding assay. Taken together,
these data provide evidence for an intramolecular interaction occurring in the
cytoplasmic domain of CD45. In the absence of the C-terminal region containing
the second phosphatase domain, intermolecular interactions occur, resulting in
dimer formation.
PMID- 9651388
TI - Increased mature interleukin-1beta (IL-1beta) secretion from THP-1 cells induced
by nigericin is a result of activation of p45 IL-1beta-converting enzyme
processing.
AB - Perregaux and Gabel (Perregaux, D., and Gabel, C. A. (1994) J. Biol. Chem. 269,
15195-15203) reported that potassium depletion of lipopolysaccharide-stimulated
mouse macrophages induced by the potassium ionophore, nigericin, leads to the
rapid release of mature interleukin-1beta (IL-1beta). We have now shown a similar
phenomenon in lipopolysaccharide-stimulated human monocytic leukemia THP-1 cells.
Rapid secretion of mature, 17-kDa IL-1beta occurred, in the presence of nigericin
(4-16 microM). No effects on the release of tumor necrosis factor-alpha, IL-6, or
proIL-1beta were seen. Addition of the irreversible interleukin-1beta-converting
enzyme (ICE) inhibitor, Z-Val-Ala-Asp-dichlorobenzoate, or a radicicol analog,
inhibited nigericin-induced mature IL-1beta release and activation of p45 ICE
precursor. The radicicol analog itself did not inhibit ICE, but markedly, and
very rapidly depleted intracellular levels of 31-kDa proIL-1beta. By contrast,
dexamethasone, cycloheximide, and the Na+/H+ antiporter inhibitor, 5-(N-ethyl-N
isopropyl)amiloride, had no effect on nigericin-induced release of IL-1beta. We
have therefore shown conclusively, for the first time, that nigericin-induced
release of IL-1beta is dependent upon activation of p45 ICE processing. So far,
the mechanism by which reduced intracellular potassium ion concentration triggers
p45 ICE processing is not known, but further investigation in this area could
lead to the discovery of novel molecular targets whereby control of IL-1beta
production might be effected.
PMID- 9651389
TI - HIV-1 Tat induces neuronal death via tumor necrosis factor-alpha and activation
of non-N-methyl-D-aspartate receptors by a NFkappaB-independent mechanism.
AB - Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous
system may result in neuronal apoptosis in vulnerable brain regions, including
cerebral cortex and basal ganglia. The mechanisms for neuronal loss are likely to
be multifactorial and indirect, since HIV-1 productively infects brain-resident
macrophages and microglia but does not cause cytolytic infection of neurons in
the central nervous system. HIV-1 infection of macrophages and microglia leads to
production and release of diffusible factors that result in neuronal cell death,
including the HIV-1 regulatory protein Tat. We demonstrate in this report that
recombinant Tat1-86 and Tat peptides containing the basic region induce neuronal
apoptosis in approximately 50% of vulnerable neurons in both rat and human
neuronal cultures, and this apoptotic cell death is mediated by release of the
pro-inflammatory cytokine tumor necrosis factor alpha, and by activation of
glutamate receptors of the non-N-methyl-D-aspartate subtype. Finally, we show
that Tat-induced apoptosis of human neuronal cell cultures occurs in the absence
of activation of the transcription factor NFkappaB. These findings further define
cellular pathways activated by Tat, that dysregulate production of tumor necrosis
factor alpha, and lead to activation of glutamate receptors and neuronal death
during HIV-1 infection of the central nervous system.
PMID- 9651390
TI - The N-terminal region of yeast TFIIB contains two adjacent functional domains
involved in stable RNA polymerase II binding and transcription start site
selection.
AB - The general transcription factor IIB (TFIIB) is required for accurate and
efficient transcription of protein-coding genes by RNA polymerase II (RNAPII). To
define functional domains in the highly conserved N-terminal region of TFIIB, we
have analyzed 14 site-directed substitution mutants of yeast TFIIB for their
ability to support cell viability, transcription in vitro, accurate start site
selection in vitro and in vivo, and to form stable complexes with purified RNAPII
in vitro. Mutations impairing the formation of stable TFIIB.RNAPII complexes
mapped to the zinc ribbon fold, whereas mutations conferring downstream shifts in
transcription start site selection were identified at multiple positions within a
highly conserved homology block adjacent and C-terminal to the zinc ribbon. These
results demonstrate that the N-terminal region of yeast TFIIB contains two
separable and adjacent functional domains involved in stable RNAPII binding and
transcription start site selection, suggesting that downstream shifts in
transcription start site selection do not result from impairment of stable
TFIIB.RNAPII binding. We discuss models for yeast start site selection in which
TFIIB may affect the ability of preinitiation complexes to interact with
downstream DNA or to affect start site recognition by a scanning polymerase.
PMID- 9651391
TI - CBP is required for sterol-regulated and sterol regulatory element-binding
protein-regulated transcription.
AB - Cells were transfected with luciferase reporter genes, under the control of
promoters derived from either the farnesyl diphosphate (FPP) synthase, 3-hydroxy
3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, or low density
lipoprotein receptor genes. The increase in luciferase activity that occurred
when cells were either incubated in sterol-depleted medium or cotransfected with
a cDNA encoding sterol regulatory element-binding protein (SREBP)-1a was
prevented by coexpression of wild-type E1A or a Gal4-CBP (1-451) fusion protein.
The inhibitory effect of E1A was overcome by coexpression of CBP. The increase in
reporter gene activity noted above was not affected when the cells were
cotransfected with cDNAs that encoded either a mutant E1A that is unable to
interact with the transcriptional activator CBP or Gal4-CBP fusion proteins
encoding separate fragments of CBP, which span the remainder of the CBP molecule.
A preformed SREBP-1a:[32P]DNA complex bound specifically to membrane-immobilized
GST-CBP fusion proteins that contained amino-terminal portions of CBP. In order
to investigate the role of CBP in the regulation of endogenous genes, we isolated
stable transformants that express Gal4-CBP(1-451) in response to added
doxycycline. Induction of endogenous FPP synthase and HMG-CoA synthase mRNAs, in
response to cellular cholesterol depletion, was prevented when cells expressed
Gal4-CBP(1-451). We conclude that when cells are incubated in the absence of
sterols, the transcriptional activation of the HMG-CoA synthase, HMG-CoA
reductase, FPP synthase, and low density lipoprotein receptor genes is dependent
on a specific interaction between SREBP, which is bound to the promoter DNA, and
the amino-terminal domain (amino acids 1-451) of CBP.
PMID- 9651392
TI - Nitroxides tempol and tempo induce divergent signal transduction pathways in MDA
MB 231 breast cancer cells.
AB - Tempol and tempo are stable free radical nitroxides that possess antioxidant
properties. In this study, we examined the effects of these compounds on
components of the mitogen-activated protein kinase signal transduction cascade.
Tempo treatment (15 min) of MDA-MB 231 human breast cancer cells resulted in
significant levels of tyrosine phosphorylation of several as yet unidentified
proteins compared with equimolar concentration of tempol (10 mM). Both compounds
caused tyrosine phosphorylation and activation of Raf-1 protein kinase (30 min, 2
3-fold). Interestingly, however, only tempol caused increased extracellular
signal-regulated kinase 1 activity (2 h, approximately 3-fold). On the other
hand, tempo, but not tempol, potently activated stress-activated protein kinase
(2 h, >3-fold). Consistent with these data, tempol was found to be noncytotoxic,
whereas tempo induced apoptotic cell death (2 h, >50%). Tempo treatment also
resulted in significant elevation of ceramide levels at 30 min (54% over control)
and 1 h (71% over control) posttreatment, preceding stress-activated protein
kinase activation and apoptosis. These data suggest that in the absence of an
environmental oxidative stress, tempol and tempo elicit distinct cellular
signaling pathways. The recognition of the molecular mechanisms of nitroxide
action may have important implications for biological effectiveness of these
compounds.
PMID- 9651393
TI - Topoisomerase IV catalysis and the mechanism of quinolone action.
AB - Topoisomerase IV is a bacterial type II topoisomerase that is essential for
proper chromosome segregation and is a target for quinolone-based antimicrobial
agents. Despite the importance of this enzyme to the survival of prokaryotic
cells and to the treatment of bacterial infections, relatively little is known
about the details of its catalytic mechanism or the basis by which quinolones
alter its enzymatic functions. Therefore, a series of experiments that analyzed
individual steps of the topoisomerase IV catalytic cycle were undertaken to
address these critical mechanistic issues. The following conclusions were drawn.
First, equilibrium levels of DNA cleavage mediated by the bacterial enzyme were
considerably (>10-fold) higher than those observed with its eukaryotic
counterparts. To a large extent, this reflected decreased rates of DNA
religation. Second, the preference of topoisomerase IV for catalyzing DNA
decatenation over relaxation reflects increased rates of strand passage and
enzyme recycling rather than a heightened recognition of intermolecular DNA
helices. Third, quinolones stimulate topoisomerase IV-mediated DNA cleavage both
by increasing rates of DNA scission and by inhibiting religation of cleaved DNA.
Finally, quinolones inhibit the overall catalytic activity of topoisomerase IV
primarily by interfering with enzyme-ATP interactions.
PMID- 9651394
TI - Functional characterization of a series of mutant G protein alphaq subunits
displaying promiscuous receptor coupling properties.
AB - The N termini of two G protein alpha subunits, alphaq and alpha11, differ from
those of other alpha subunits in that they display a unique, highly conserved six
amino acid extension (MTLESI(M)). We recently showed that an alphaq deletion
mutant lacking these six amino acids (in contrast to wild type alphaq) was able
to couple to several different Gs- and Gi/o-coupled receptors, apparently due to
promiscuous receptor/G protein coupling (Kostenis, E., Degtyarev, M. Y., Conklin,
B. R., and Wess, J. (1997) J. Biol. Chem. 272, 19107-19110). To study which
specific amino acids within the N-terminal segment of alphaq/11 are critical for
constraining the receptor coupling selectivity of these subunits, this region of
alphaq was subjected to systematic deletion and alanine scanning mutagenesis. All
mutant alphaq constructs (or wild type alphaq as a control) were coexpressed (in
COS-7 cells) with the m2 muscarinic or the D2 dopamine receptors, two
prototypical Gi/o-coupled receptors, and ligand-induced increases in inositol
phosphate production were determined as a measure of G protein activation.
Surprisingly, all 14 mutant G proteins studied (but not wild type alphaq) gained
the ability to productively interact with the two Gi/o-linked receptors. Similar
results were obtained when we examined the ability of selected mutant alphaq
subunits to couple to the Gs-coupled beta2-adrenergic receptor. Additional
experiments indicated that the functional promiscuity displayed by all
investigated mutant alphaq constructs was not due to overexpression (as compared
with wild type alphaq), lack of palmitoylation, or initiation of translation at a
downstream ATG codon (codon seven). These data are consistent with the notion
that the six-amino acid extension characteristic for alphaq/11 subunits forms a
tightly folded protein subdomain that is critical for regulating the receptor
coupling selectivity of these subunits.
PMID- 9651395
TI - Cloning and characterization of a novel matrix metalloproteinase (MMP), CMMP,
from chicken embryo fibroblasts. CMMP, Xenopus XMMP, and human MMP19 have a
conserved unique cysteine in the catalytic domain.
AB - We cloned a novel matrix metalloproteinase (MMP) called CMMP from cultured
primary chicken embryo fibroblasts. The cDNA-derived CMMP sequence contains 472
amino acids including a putative 19-residue signal peptide and a unique cysteine
in the catalytic domain, an insertion in a sequence motif that binds the
structural (noncatalytic) zinc of MMPs. Strikingly, a homologously inserted
cysteine is also found in Xenopus XMMP and human MMP19, two recently cloned novel
members of the MMP family. Phylogenetic analysis suggest that XMMP and MMP19
represent founding members of the MMP family, whereas CMMP is related to
collagenase MMPs. Bacterially produced recombinant CMMP (without the amino
terminal inhibition domain), which was autoproteolyzed at the carboxyl-terminal
domain, digested casein and gelatin. As shown by Northern blotting, CMMP mRNA of
1.8 kilobase pairs was constitutively expressed in cultured primary chicken
embryo fibroblasts and up-regulated by tumor necrosis factor-alpha and the
phorbol ester 12-O-tetradecanoylphorbol-13-acetate, but it was not regulated by
interleukin-1, basic fibroblast growth factor, or retinoic acid. CMMP mRNA of 1.8
kb was also detected in the head and body of 8-day-old chicken embryos and
dramatically up-regulated in 9-day-old embryos.
PMID- 9651396
TI - Crucial role of N terminus in function of cardiac L-type Ca2+ channel and its
modulation by protein kinase C.
AB - The role of the cytosolic N terminus of the main subunit (alpha1C) of cardiac L
type voltage-dependent Ca2+ channel was studied in Xenopus oocyte expression
system. Deletion of the initial 46 or 139 amino acids (a.a.) of rabbit heart
alpha1C caused a 5-10-fold increase in the whole cell Ca2+ channel current
carried by Ba2+ (IBa), as reported previously (Wei, X., Neely, A., Olcese, R.,
Lang, W., Stefani, E., and Birnbaumer, L. (1996) Recept. Channels 4, 205-215).
The plasma membrane content of alpha1C protein, measured immunochemically, was
not altered by the 46-a.a. deletion. Patch clamp recordings in the presence of a
dihydropyridine agonist showed that this deletion causes a approximately 10-fold
increase in single channel open probability without changing channel density.
Thus, the initial segment of the N terminus affects channel gating rather than
expression. The increase in IBa caused by coexpression of the auxiliary beta2A
subunit was substantially stronger in channels with full-length alpha1C than in
46- or 139-a.a. truncated mutants, suggesting an interaction between beta2A and N
terminus. However, only the I-II domain linker of alpha1C, but not to N or C
termini, bound beta2A in vitro. The well documented increase of IBa caused by
activation of protein kinase C (PKC) was fully eliminated by the 46-a.a.
deletion. Thus, the N terminus of alpha1C plays a crucial role in channel gating
and PKC modulation. We propose that PKC and beta subunit enhance the activity of
the channel in part by relieving an inhibitory control exerted by the N terminus.
Since PKC up-regulation of L-type Ca2+ channels has been reported in many
species, we predict that isoforms of alpha1C subunits containing the initial N
terminal 46 a.a. similar to those of the rabbit heart alpha1C are widespread in
cardiac and smooth muscle cells.
PMID- 9651397
TI - cDNA cloning, tissue distribution, and substrate characteristics of a cis
Retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme.
AB - We report here a mouse cDNA that encodes a 316-amino acid short-chain
dehydrogenase that prefers NAD+ as its cofactor and recognizes as substrates
androgens and retinols, i.e. has steroid 3alpha- and 17beta-dehydrogenase and
cis/trans-retinol catalytic activities. This cis-retinol/androgen dehydrogenase
type 2 (CRAD2) shares close amino acid similarity with mouse retinol
dehydrogenase isozyme types 1 and 2 and CRAD1 (86, 84, and 87%, respectively).
CRAD2 exhibits cooperative kinetics with 3alpha-adiol (3alpha-hydroxysteroid
dehydrogenase activity) and testosterone (17beta-hydroxysteroid dehydrogenase
activity), but Michaelis-Menten kinetics with androsterone (3alpha-hydroxysteroid
dehydrogenase activity), 11-cis-retinol, all-trans-retinol, and 9-cis-retinol,
with V/K0.5 values of 1.6, 0.2, 0.1, 0.04, 0.005, and not saturated,
respectively. Carbenoxolone (IC50 = 2 microM) and 4-methylpyrazole (IC50 = 5 mM)
inhibited CRAD2, but neither ethanol nor phosphatidylcholine had marked effects
on its activity. Liver expressed CRAD2 mRNA intensely, with expression in lung,
eye, kidney, and brain (2.9, 2, 1.6, and 0.6% of liver mRNA, respectively). CRAD2
represents the fifth isozyme in a group of short-chain dehydrogenase/reductase
isozymes (retinol dehydrogenases 1-3 and CRAD1), closely related in primary amino
acid sequence (approximately 85%), that are expressed in different quantities in
various tissues, have different substrate specificities, and may serve different
physiological functions. CRAD2 may alter the amounts of active and inactive
androgens and/or convert retinols into retinals. These data expand insight into
the multifunctional nature of short-chain dehydrogenases/reductases and into the
enzymology of steroid and retinoid metabolism.
PMID- 9651399
TI - A potent cell death activity associated with transient high level expression of
BCL-2.
AB - The BCL-2 proto-oncogene contains unusually long untranslated 5' and 3'
sequences. Deletion of the sequences flanking the BCL-2 open reading frame
dramatically increases the level of protein expression. Transient high level BCL
2 protein expression mediated by plasmid transfection or by infection with
recombinant adenovirus results in potent apoptosis of several cell lines.
Detailed mutational (deletion and add-back) analysis reveals that both 5'- and 3'
flanking sequences contribute to the negative modulation of protein expression
from the BCL-2 open reading frame. It appears that these sequences exert the
negative regulatory effect in an orientation-dependent manner. Analysis of BCL-2
RNA levels indicate that elevated levels of mRNA may be the primary cause of
elevated levels of protein expression. Apoptosis induced by adenovirus vectors
expressing elevated levels of BCL-2 can be readily inhibited by the caspase
inhibitor z-VAD-fmk, suggesting that high levels of BCL-2 expression induce
apoptosis via the caspase cascade. Mutational analysis of BCL-2 indicates that
its pro-apoptotic activity is separable from its anti-apoptosis activity. Our
results raise the possibility that oncogenic conversion of BCL-2 may require
somatic mutations in the pro-apoptotic activity, in addition to other activating
mutations that result in enhanced expression. Consistent with this hypothesis, a
somatic mutation of BCL-2 observed in multiple human tumors results in reduced
apoptosis activity.
PMID- 9651400
TI - Biochemical coupling between the DrrA and DrrB proteins of the doxorubicin efflux
pump of Streptomyces peucetius.
AB - The drrAB operon of Streptomyces peucetius encodes for resistance to the
antibiotics doxorubicin and daunorubicin. Subcloning of the drrAB genes in
Escherichia coli has previously been shown to result in expression of DrrA and
DrrB proteins and resistance to doxorubicin in a sensitive strain of E. coli.
DrrA, a peripheral membrane protein, binds ATP in a UV-catalyzed reaction in a
doxorubicin-dependent manner; DrrB, a hydrophobic protein, is localized to the
inner membrane of E. coli (Kaur, P. (1997) J. Bacteriol. 179, 569-575). The
present study provides evidence that DrrB, the membrane component of the complex,
is stably maintained in the cell only if DrrA is present. Furthermore, it was
found that the catalytic component DrrA is in an active conformation only when it
is in a complex with DrrB. In a subclone containing the drrB gene by itself, no
DrrB protein could be detected, although a translational fusion of the first 15
amino acids of DrrB to beta-galactosidase indicated that DrrB is translated in
the absence of DrrA. Upon co-transformation with a plasmid containing the drrA
gene in trans, DrrB could again be detected in these cells. UV cross-linking
studies with [alpha-32P]ATP showed that only the membrane-bound form of DrrA in
cells containing both DrrA and DrrB was in a conformation competent to bind ATP.
Chemical cross-linking studies also provided direct evidence for interaction
between the two proteins. Based on these analyses, a model for interaction
between DrrA and DrrB proteins is presented.
PMID- 9651398
TI - The gut-enriched Kruppel-like factor suppresses the activity of the CYP1A1
promoter in an Sp1-dependent fashion.
AB - The gut-enriched Kruppel-like factor (GKLF) is a newly identified zinc finger
containing transcription factor. Recent studies indicate that GKLF binds to a
core DNA sequence of 5'-(G/A)(G/A)GG(C/T)G(C/T)-3', which is found in an
endogenous cis element, the basic transcription element (BTE) of the cytochrome P
450IA1 (CYP1A1) promoter. The present study characterizes the ability of GKLF to
regulate CYP1A1 expression. By electrophoretic mobility gel shift assay (EMSA)
and methylation interference assay, GKLF was found to bind BTE in a manner
similar to several other transcription factors known to interact with BTE
including Sp1 and BTEB. Cotransfection studies in Chinese hamster ovary cells
showed that GKLF inhibited the CYP1A1 promoter in a dose- and BTE-dependent
manner. The same experiments also revealed that BTE was responsible for a
significant portion of the CYP1A1 promoter activity. EMSA of nuclear extracts
from Chinese hamster ovary cells showed that Sp1 and Sp3 were two major proteins
that interacted with BTE. Additional cotransfection studies showed that GKLF
inhibited Sp1-mediated activation of the CYP1A1 promoter. In contrast, GKLF
enhanced Sp3-dependent suppression of the same promoter. Moreover, the ability of
GKLF to inhibit Sp1-dependent transactivation was in part due to physical
interaction of the two proteins. These findings indicate that GKLF is a negative
regulator of the CYP1A1 promoter in a BTE-dependent fashion and that this
inhibitory effect is in part mediated by physical interaction with Sp1.
PMID- 9651401
TI - Identification of the hepatic protein targets of reactive metabolites of
acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass
spectrometry.
AB - Liver toxicity following an overdose of acetaminophen is frequently considered a
model for drug-induced hepatotoxicity. Extensive studies over many years have
established that such toxicity is well correlated with liver protein arylation by
acetaminophen metabolites. Identification of protein targets for covalent
modifications is a challenging but necessary step in understanding how covalent
binding could lead to liver toxicity. Previous approaches suffered from technical
limitations, and thus over the last 10 years heroic efforts were required to
determine the identity of only a few target proteins. We present a new mass
spectrometry-based strategy for identification of all target proteins that now
provides a comprehensive survey of the suite of liver proteins modified. After
administration of radiolabeled acetaminophen to mice, the proteins in the liver
tissue lysate were separated by two-dimensional polyacrylamide gel
electrophoresis. In-gel digestion of the radiolabeled gel spots gave a set of
tryptic peptides, which were analyzed by matrix-assisted laser desorption
ionization mass spectrometry. Interrogation of data bases based on experimentally
determined molecular weights of peptides and product ion tags from postsource
decay mass spectra was employed for the determination of the identities of
modified liver proteins. Using this method, more than 20 new drug-labeled
proteins have been identified.
PMID- 9651402
TI - Involvement of retinoic acid/retinoid receptors in the regulation of murine
alphaB-crystallin/small heat shock protein gene expression in the lens.
AB - Crystallins are a diverse group of abundant soluble proteins that are responsible
for the refractive properties of the transparent eye lens. We showed previously
that Pax-6 can activate the alphaB-crystallin/small heat shock protein promoter
via the lens-specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46).
Here we demonstrate that retinoic acid can induce the accumulation of alphaB
crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers
(retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and
LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated
that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid
response elements within LSR1 and LSR2. Electrophoretic mobility shift assays
using antibodies indicated that LSR1 and LSR2 can interact with endogenous
RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together
had an additive effect on the activation of alphaB-promoter in the transfected
lens cells. Thus, the alphaB-crystallin gene is activated by Pax-6 and retinoic
acid receptors, making these transcription factors examples of proteins that have
critical roles in early development as well as in the expression of proteins
characterizing terminal differentiation.
PMID- 9651403
TI - Structure-function relationships in OxlT, the oxalate/formate transporter of
Oxalobacter formigenes. Topological features of transmembrane helix 11 as
visualized by site-directed fluorescent labeling.
AB - Analysis of hydropathy suggests that in OxlT, the oxalate/formate antiporter of
Oxalobacter formigenes, lysine 355 is within transmembrane helix no. 11. To test
this idea, we used single-cysteine, histidine-tagged OxlT variants to study the
organization of a 30-residue segment (residues 344-373) containing this region.
Topology was examined by probing the A345C and A370C proteins with Oregon Green
maleimide carboxylic acid, an impermeant and fluorescent thiol-reactive agent.
Examination of purified protein showed that only A370C was fluorescent after
treating intact cells with the probe, while both proteins were modified in tests
with isolated membrane ghosts. In addition, labeling of A370C, but not A345C, was
blocked when external cysteines were protected with the impermeant and
nonfluorescent agent, methanethiosulfonate ethyltrimethylammonium. These findings
confirm that A345 faces the cytoplasm, while A370C faces the periplasm. A similar
study focused on 13 single-cysteine variants positioned throughout the target
segment. That work revealed a striking discontinuity in reactivity toward Oregon
Green maleimide; cysteines within a 10-residue central core (residues 351-360)
were not labeled when membranes were probed, but were readily modified after
protein denaturation. We suggest this core resides within the lipid bilayer,
unavailable to an impermeant reporter. Since this region includes position 355,
we also suggest that lysine 355 lies within the OxlT hydrophobic sector, where it
may facilitate the binding and translocation of the anionic substrates, oxalate
and formate.
PMID- 9651404
TI - Identification of an insulin-responsive, slow endocytic recycling mechanism in
Chinese hamster ovary cells.
AB - In adipocytes, the insulin-regulated aminopeptidase (IRAP) is trafficked through
the same insulin-regulated recycling pathway as the GLUT4 glucose transporter. We
find that a chimera, containing the cytoplasmic domain of IRAP fused to
transmembrane and extracellular domains of the transferrin receptor, is slowly
recycled and rapidly internalized in Chinese hamster ovary cells. Morphological
studies indicate that the chimera is slowly trafficked through the general
endosomal recycling compartment rather than being sorted to a specialized
recycling pathway. A chimera in which a di-leucine sequence within the
cytoplasmic domain of IRAP has been mutated to alanines is rapidly internalized
and rapidly recycled, indicating that this di-leucine is required for the slow
recycling but not for the rapid internalization. Insulin stimulates a 2-3-fold
increase in the recycling of the chimera and only a 1.2-fold increase in the
recycling of the transferrin receptor. The effect of insulin on the recycling of
the chimera is blocked by wortmannin, a phosphatidylinositol 3'-kinase inhibitor.
GTPgammaS (guanosine 5'-3-O-(thio)triphosphate) increases the recycling of the
chimera by 50% but has no effect on the recycling of the transferrin receptor. In
these studies, we have identified in Chinese hamster ovary cells a novel, slow
endocytic recycling mechanism that is regulated by insulin.
PMID- 9651405
TI - Zinc supplementation reduces the incidence of acute lower respiratory infections
in infants and preschool children: a double-blind, controlled trial.
AB - BACKGROUND: Increased acute lower respiratory infection incidence, severity, and
mortality are associated with malnutrition, and reduced immunological competence
may be a mechanism for this association. Because zinc deficiency results in
impaired immunocompetence and zinc supplementation improves immune status, we
hypothesized that zinc deficiency is associated with increased incidence and
severity of acute lower respiratory infection. METHODS: We evaluated the effect
of daily supplementation with 10 mg of elemental zinc on the incidence and
prevalence of acute lower respiratory infection in a double-blind, randomized,
controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months
of age. Supplementation and morbidity surveillance were done for 6 months.
RESULTS: After 120 days of supplementation, the percentage of children with
plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the
zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc
supplemented children had 0.19 acute lower respiratory infection
episodes/child/year compared with 0.35 episodes/child/year in the control
children. After correction for correlation of data using generalized estimating
equation regression methods, there was a reduction of 45% (95% confidence
interval, 10% to 67%) in the incidence of acute lower respiratory infections in
zinc-supplemented children. CONCLUSIONS: A dietary zinc supplement resulted in a
significant reduction in respiratory morbidity in preschool children. These
findings suggest that interventions to improve zinc intake will improve the
health and survival of children in developing countries.
PMID- 9651406
TI - A randomized, placebo-controlled trial of granulocyte colony-stimulating factor
administration to newborn infants with neutropenia and clinical signs of early
onset sepsis.
AB - OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating
factor (G-CSF) administration: 1) accelerates production of neutrophils; 2)
increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn
infants with neutropenia and clinical signs of early-onset sepsis. STUDY DESIGN:
We randomized 20 infants with neutropenia and clinical signs of early-onset
sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo
for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an
elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement
for ventilatory support. Cultures were obtained and antibiotics initiated on all
study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone
marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and
plasma G-CSF concentrations were evaluated. Also, severity of illness as
determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and
mortality were recorded. RESULTS: Circulating ANC increased in both G-CSF and
placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G
CSF and placebo recipients. There were no significant differences in the ANC or
I/T ratio between the two groups during the study period. Similarly, bone marrow
NSP and NPP did not differ between G-CSF and placebo recipients at study entry or
day 2. No differences were observed in the secondary outcome measures including
severity of illness, morbidity, and mortality. CONCLUSIONS: Administration of
recombinant G-CSF to infants with neutropenia and clinical signs of early-onset
sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with
placebo. No differences were observed between G-CSF and placebo recipients in
severity of illness, morbidity, or mortality. No adverse effects of G-CSF
administrations were noted.
PMID- 9651407
TI - Course of tic severity in Tourette syndrome: the first two decades.
AB - OBJECTIVE: Prevalence studies indicate a 10-fold higher rate of Tourette syndrome
(TS) among children compared with adults. The purpose of this investigation was
to examine the course of tic severity during the first 2 decades of life. METHOD:
A birth-year cohort of 42 TS patients followed at the Yale Child Study Center was
recontacted an average of 7.3 years after their initial clinical evaluation. Data
concerning the onset and course of tic severity until 18 years of age were
available on 36 TS patients. A variety of statistical techniques were used to
model aspects of the temporal patterning of tic severity. RESULTS: Mean (SD) tic
onset at 5.6 (2. 3) years of age was followed by a progressive pattern of tic
worsening. On average, the most severe period of tic severity occurred at 10.0
(2.4) years of age. In eight cases (22%), the frequency and forcefulness of the
tics reached a severe level during the worst-ever period such that functioning in
school was impossible or in serious jeopardy. In almost every case this period
was followed by a steady decline in tic severity. By 18 years of age nearly half
of the cohort was virtually tic-free. The onset of puberty was not associated
with either the timing or severity of tics. CONCLUSIONS: A majority of TS
patients displayed a consistent time course of tic severity. This consistency can
be accurately modeled mathematically and may reflect normal neurobiological
processes. Determination of the model parameters that describe each patient's
course of tic severity may be of prognostic value and assist in the
identification of factors that differentially influence the course of tic
severity.
PMID- 9651408
TI - Decreasing nonurgent emergency department utilization by Medicaid children.
AB - OBJECTIVE: To test interventions to decrease the utilization of hospital
emergency departments (EDs) for routine, nonemergent health care among Medicaid
recipients. METHODS: Families of a Medicaid-recipient child presenting to a
children's hospital ED for nonurgent problems received information from either a
health professional or a clerical employee about the importance of a primary care
provider and assistance with making an appointment to the provider of their
choice. The health professional continued to work with her assigned families in
eliminating barriers to appropriate utilization of a primary care provider for up
to 3 months after the index ED visit. A third (comparison) group received no
intervention. Subsequent health care utilization for each enrollee was tracked
via Ohio Medicaid claims data throughout the four subsequent 6-month periods
after the index ED visit. RESULTS: Children in the intervention groups had 11.1%
and 14.5% fewer nonurgent ED visits in the 6 months after the index ED visit with
a concomitant decrease in cost for this type of care when compared with the
comparison group during the same time period. No difference in the number of
preventive or ill-child primary care visits was seen. There was no difference in
health care cost or utilization in the time period 6 to 24 months after the
intervention. CONCLUSIONS: Interventions in pediatric EDs aimed at decreasing
subsequent ED utilization for nonurgent care can be effective, resulting in
modest decreases in the cost of health care for a Medicaid population.
PMID- 9651409
TI - The association between adequacy of prenatal care utilization and subsequent
pediatric care utilization in the United States.
AB - OBJECTIVE: To explore the association between adequacy of prenatal care
utilization and subsequent pediatric care utilization. DESIGN: A longitudinal
follow-up of a nationally representative sample of infants born in 1988.
PARTICIPANTS: Nine thousand four hundred forty women who had a live birth in
1988, and whose child was alive at the time of interview, and 8285 women from the
original sample who were reinterviewed in 1991. MAIN OUTCOME MEASURE: There were
four outcome measures: number of well-child visits; adequate immunization for
diphtheria, tetanus, and pertussis; adequate immunization for polio; and
continuity of a regular source of care, as measured by the number of sites for
pediatric care. RESULTS: Children whose mothers had less than adequate prenatal
care utilization had significantly fewer well-child visits, and were
significantly less likely to have adequate immunizations, even after income,
health insurance coverage, content of prenatal care, wantedness of child, sites
of prenatal and pediatric care, and maternal and pregnancy risk characteristics
were taken into account. Less than adequate prenatal care utilization was not
associated with having more than one pediatric care site. CONCLUSIONS: Prenatal
care utilization can be used to identify and target interventions to women who
are at risk for not obtaining well-child care or complete immunizations for their
children.
PMID- 9651410
TI - Should fewer premature infants be screened for retinopathy of prematurity in the
managed care era?
AB - OBJECTIVE: To determine appropriate upper limits for gestational age and birth
weight when screening infants for retinopathy of prematurity (ROP). DESIGN:
Retrospective survey. SETTING: Tertiary neonatal intensive care nursery.
PATIENTS: Seven hundred seven infants born July 1, 1990 to June 30, 1996 and
screened for ROP according to the 1988 to 1996 American Academy of Pediatrics
guidelines. OUTCOME MEASURES: Maximum stage of ROP with respect to birth weight
and gestational age. RESULTS: No ROP more than Stage 1 was observed in infants
with gestational ages >/=32 weeks or birth weights >/=1500 g. All cases of
threshold and Stage 4 ROP were confined to infants with gestational ages =30
weeks or birth weights <1200 g. CONCLUSIONS: The latest American Academy of
Pediatrics screening guidelines for ROP are discretionary for infants with birth
weights >1500 g or gestational ages >28 weeks. If ROP screening is limited to
infants with birth weights of =1500 g, 34.2% fewer infants would require
screening compared with the previous <1800 g recommendation, while missing no
cases of ROP more than Stage 1. A gestational age cut-off of =28 weeks,
however, is less desirable, and could potentially miss several infants with more
advanced retinopathy (including Stage 4). If ROP screening criteria were instead
modified to include infants of gestational ages <32 weeks, the number of patients
requiring screening could be reduced 29.1% compared with the previous
recommendation of <35 weeks, again without missing any cases of ROP more than
Stage 1. Use of such a screening strategy (birth weight <1500 g or gestational
age <32 weeks) is predicted to save in excess of 1.5 million dollars annually in
the United States, while missing no cases of ROP more than Stage 1.
PMID- 9651411
TI - Cost-effectiveness of care for very low birth weight infants.
AB - OBJECTIVE: Very low birth weight (VLBW)infants (those with birth weights <1500 g)
account for only 1.2% of births but 46% of infant deaths. Large improvements in
neonatal technology in the last 2 decades have significantly improved survival
prospects for infants with low birth weights, but at a high cost. Due largely to
a lack of data, the costs of medical care during the period in which infant
mortality is measured (the first year of life), as well as the cost-effectiveness
of that care for VLBW infants, have not been quantified. Despite this fact,
public policies both toward providing insurance coverage for their care, as well
as denying payment for their treatment, have either been proposed or implemented
on cost-effectiveness grounds. PATIENTS: The study includes all VLBW single live
births in the state of California during 1986 and 1987 that were continuously
eligible (through traditional channels) for the state's Medicaid program. MAIN
OUTCOME MEASURES: Treatment costs were measured for all medical care received
during the first year of life, including all inpatient and outpatient care
received. The cost-effectiveness of care is measured by aggregate treatment costs
for all singleton VLBW liveborns divided by the number of first-year survivors.
RESULTS: Average treatment costs per first-year survivor for infants <1500 g was
$93 800 (in 1987 constant dollars). Treatment costs per survivor were twice as
high for infants <750 g ($273 900) as for the next highest birth weight group 750
to 999 g ($138 800) which was itself almost twice as high as for the 1000 to 1249
g group ($75 100). The gradient in cost-effectiveness with birth weight then
drops off to $58 000 per survivor for infants with birth weights between 1250 and
1499 g. CONCLUSION: Public policies aimed at improving birth outcomes by
providing insurance coverage for pregnant women and children, such as the recent
Medicaid expansions, can potentially be very cost-effective. Although maternal
interventions such as prenatal care are relatively inexpensive, each normal birth
that results instead in a VLBW birth saves $59 700 in first year medical
expenses. However, cost savings attributable to increased birth weights depend on
where in the birth weight distribution the increase occurs as well as the size of
the birth weight increase. For infants with birth weights >750 g, significant
gains can accrue from even a small shift in the birth weight distribution. A
shift of 250 g at birth saves an average of $12 000 to $16 000 in first year
medical costs and a shift of 500 g generates $28 000 in savings. However, there
is a threshold effect on birth weight. For infants <750 g, increases in birth
weight may increase medical expenditures. For instance, a shift in birth weight
to the 750 to 999 g range increases costs by $29 000.
PMID- 9651412
TI - Cystic fibrosis newborn screening: impact on reproductive behavior and
implications for genetic counseling.
AB - OBJECTIVE: To evaluate the impact of newborn screening for cystic fibrosis (CF)
on the reproductive knowledge and behavior of CF families and to determine if
heterozygote detection with the immunoreactive trypsinogen (IRT) method in
conjunction with DNA analysis (IRT/DNA) influences knowledge and attitudes about
reproduction in false-positive families. METHODS: The Wisconsin CF Neonatal
Screening Project investigated 650 340 infants from 1985 to 1994 in a
comprehensive randomized controlled trial to study both benefits and risks of
newborn screening and to determine if early diagnosis would improve the prognosis
of children with CF. Assessments of reproductive knowledge, attitudes, and
behaviors of 135 families of children diagnosed as having CF in both the early
treatment group and control groups were made 3 months after diagnosis using a
questionnaire which was completed by 100 families. The same questionnaire was
administered 1 year later to evaluate retention of information. It was completed
by 71 families. A follow-up assessment tool was also administered in 1994 and
responses obtained from 73 families. Knowledge, attitudes, and behavior among
false-positive families were also assessed at the time of the sweat test in 206
families who experienced IRT screening and 109 families tested with the IRT/DNA
method. Follow-up assessments were completed 1 year later in 106 IRT families and
63 IRT/DNA families. RESULTS: In families with a CF child, 95% initially
understood that there was a 1 in 4 risk in subsequent pregnancies, and there was
good retention of this information 1 year later. At the 1994 assessment, 52% of
families had not yet conceived more children, but 74% of these already had
children. In the couples in whom CF was diagnosed in the first child, 70% (95%
confidence interval = 54% to 85%) conceived more children. There were 43
subsequent pregnancies in 31 families. Prenatal diagnosis was used by 26% of the
families (8/31) for 21% of the pregnancies (9/43). There were 3 pregnancies with
CF detected, all of which were carried to term. In the false-positive groups,
>95% of families initially understood that their child definitely did not have
CF. There was no difference between false-positive IRT and IRT/DNA groups, and
the information was retained at 1 year. Follow-up assessment 1 year after
negative sweat tests revealed that 7% of the IRT and 10% of the IRT/DNA families
still thought about the results often or constantly. When asked whether the
experience of screening affected feelings about having more children, an
affirmative response was obtained in 4% of IRT families but in 17% of IRT/DNA
families. One year later, more than half of the false-positive IRT/DNA families
did not understand that they were at increased risk of having a child with CF.
CONCLUSIONS: We conclude that CF neonatal screening does not have a significant
impact on the reproductive behavior of most families and that prenatal diagnosis
is not used by the majority of CF families. IRT/DNA testing experiences seem to
affect attitudes about having more children, and some parents are confused about
the implications of the results, even with genetic counseling. However,
persistent concerns about the sweat test result are limited. Questions raised by
this study confirm the need for more research regarding the process of genetic
counseling and its impact on reproductive attitudes and behavior in the newborn
screening setting.
PMID- 9651413
TI - Documentation of child physical abuse: how far have we come?
AB - OBJECTIVES: To determine the effects of increased physician training and a
structured clinical form on physician documentation of child physical abuse.
DESIGN: Retrospective chart review. PARTICIPANTS: Children evaluated in the
pediatric emergency department in 1980 and 1995 who were given the diagnosis of
physical abuse. MEASUREMENTS: The unstructured pediatric emergency department
form and the structured child abuse reporting form were reviewed for
documentation of 20 items including history, physical examination, diagnostic
procedures, and disposition. Data documented in 1980 were compared with that in
1995. RESULTS: The only significant differences between 1980 and 1995 concerning
documentation on the unstructured pediatric emergency department form were better
recording in the latter year of Child Protective Services involvement and case
disposition. Half or more of the records omitted documentation of at least one of
the following: witnesses to injury, past injuries, description of size and/or
color of injuries, illustration, and a genital exam. None of the records
contained a developmental history. Significantly fewer skeletal surveys were
obtained in 1995, although notation of the results was similar to 1980. For both
years, the structured child abuse reporting form improved documentation of only
two items: time of arrival to the pediatric emergency department and
illustrations of injuries. CONCLUSIONS: Little improvement in physician
documentation of child physical abuse was noted between 1980 and 1995 despite
increased efforts to educate housestaff in the evaluation of child abuse during
this time period. Although a structured form prompted physicians to document
dates and times and to illustrate physical injuries on the diagram provided, it
did not significantly improve documentation of other items.
PMID- 9651414
TI - Pharmacologic and psychologic interventions for procedural pain.
AB - OBJECTIVE: This study evaluated a combined pharmacologic and psychologic
intervention (combined intervention, CI) relative to a pharmacologic-only (PO)
intervention in reducing child distress during invasive procedures in childhood
leukemia. Predictors of child distress included age, group (CI, PO), and
procedural variables (medications and doses, technical difficulty, number of
needles required). METHODOLOGY: This was a randomized, controlled prospective
study that compared the PO (n = 45) and CI arms (n = 47), at 1, 6, and >12 months
after diagnosis. A cross-sectional control group consisted of parents of 70
patients in first remission before the prospective study. Parent questionnaires,
staff and parent ratings, and data on medications administered, technical
difficulty of the procedure, and needle insertions were obtained for each
procedure. This article reports on the final data point for the project (>12
months). RESULTS: Mothers and nurses reported lower levels of child distress in
the CI than the PO group. The CI and PO groups showed lower levels of child and
parent distress than the cross-sectional control group. Distress decreased
throughout the time, and child age was inversely related to distress (younger
children had more distress) regardless of group. Child distress was associated
with staff perceptions of the technical difficulty of the procedure and with
child age, but not with medications administered. CONCLUSIONS: The data showed
that pharmacologic and psychologic interventions for procedural distress were
effective in reducing child and parent distress and support integration of the
two approaches. Younger children experienced more distress and warranted
additional consideration. Staff perceptions of the technical difficulty of
procedures were complex and potentially helpful in designing intervention
protocols.
PMID- 9651416
TI - A retrospective review of pediatric patients with epididymitis, testicular
torsion, and torsion of testicular appendages.
AB - STUDY OBJECTIVE: To compare historical features, physical examination findings,
and testicular color Doppler ultrasound in pediatric patients with epididymitis,
testicular torsion, and torsion of appendix testis. METHODS: A retrospective
review of patients with the diagnosis of epididymitis, testicular torsion, or
torsion of appendix testis. RESULTS: Ninety patients were included in the study
(64 with epididymitis, 13 with testicular torsion, and 13 with torsion of
appendix testis). Historical features did not differ among groups except for
duration of symptoms. Of 13 patients with testicular torsion all had a tender
testicle and an absent cremasteric reflex. When compared with the testicular
torsion group, fewer patients with epididymitis had a tender testicle (69%) or an
absent cremasteric reflex (14%). 62 (97%) patients with epididymitis had a tender
epididymis and 43 (67%) had scrotal erythema/edema. By comparison, 3 (23%) and 5
(38%) patients with testicular torsion had a tender epididymis or scrotal
erythema/edema, respectively. Doppler ultrasound showed decreased or absent blood
flow in 8 patients, 7 of whom were diagnosed with testicular torsion. Ten out of
13 patients with testicular torsion had a salvageable testicle at the time of
surgery. CONCLUSION: The physical examination is helpful in distinguishing among
epididymitis, testicular torsion, and torsion of appendix testis. Patients
presenting with a tender testicle and an absent cremasteric reflex were more
likely to have a testicular torsion rather than epididymitis or torsion of
appendix testis. An absent cremasteric reflex was the most sensitive physical
finding for diagnosing testicular torsion. Color Doppler ultrasound is a useful
adjunct in the evaluation of the acute scrotum when physical findings are
equivocal.
PMID- 9651415
TI - Occult bacteremia with group B streptococci in an outpatient setting.
AB - OBJECTIVES: We undertook this study to determine the relative frequency of occult
bacteremia with group B streptococci (GBS) and to define the clinical features of
infants with occult bacteremia attributable to GBS at the time of initial
clinical contact. DESIGN: The logs of the microbiology laboratory were reviewed
for blood and cerebrospinal fluid isolates of GBS from 1982 to 1996. Records of
patients identified with GBS were abstracted. Patients were classified as having
occult bacteremia if GBS were isolated from their blood and they seemed nontoxic
and had no apparent clinical or laboratory evidence of focal infection. All other
patients were diagnosed with sepsis, meningitis, or nonmeningeal foci. RESULTS:
We reviewed the medical records of 147 children with GBS and identified 108
outpatients, including 47 (44%) with occult bacteremia, 42 (39%) with meningitis,
11 (10%) with nonmeningeal foci, and 8 (7%) with sepsis. Compared with patients
with sepsis or focal infections, those with occult bacteremia were older (61.1 vs
39.1 days) and had slightly, although not significantly, higher white blood cell
(WBC) counts (13 280 +/- 6854 vs 10 688 +/- 8574), but similar degrees of fever.
Among the 47 patients with occult bacteremia, none died, as compared with 2 of 61
with serious infections, and fewer had neurologic sequelae (0/47 vs 11/61).
Patients with occult bacteremia >90 days of age generally had temperatures >39
degreesC (9/11, mean 39.3 degreesC) and WBC counts >15 000/mm3 (7/10, mean 19
070/mm3), both of which differed significantly compared with those who were <90
days of age. Thirty of the 47 patients with occult bacteremia received
intravenous antibiotics and recovered. One of 8 patients discharged without
antibiotics and none of 8 with antibiotics developed a focal complication; 1
discharged patient was lost to follow-up. CONCLUSIONS: Almost one-half of the
children with GBS disease beyond the immediate neonatal period had occult
bacteremia. Among 8 untreated patients with bacteremia, 1 developed a focal
complication. Although the small proportion of children with GBS occult
bacteremia who were >90 days of age usually had the risk factors of temperature
>39 degrees C and WBC >15 000/mm3, as seen with occult bacteremia attributable to
other organisms, the majority of the patients who were younger did not have a
characteristic clinical syndrome. Prevention of sequelae in these young infants
will require a low threshold for diagnosis and treatment.
PMID- 9651417
TI - Asthma in non-inner city Head Start children.
AB - OBJECTIVE: Asthma is a significant cause of morbidity and mortality in children.
The objective of this study was to determine whether the federal program Head
Start in Dane County, Wisconsin, could be used as a mechanism to identify
preschool-aged children with asthma. DESIGN: Five-year, cross-sectional survey of
parents with children enrolled in Head Start. METHODS: Investigator-administered
asthma screening questionnaire to parents of enrolling Head Start children in
Dane County, Wisconsin. MEASUREMENTS: Asthma prevalence and asthma-related health
care use, including emergency department visits, hospitalizations, and medication
usage, were measured using an asthma screening questionnaire developed by
investigators. RESULTS: Information was gathered on 2215 children. The prevalence
of physician-diagnosed asthma in the screened children was 15.8%. Parental
reports of physician-diagnosed asthma were validated in a subset of 133 children,
with a 98.5% confirmation rate. Independent risk factors for asthma included male
gender (relative risk, 1.4) and African-American ethnicity (relative risk, 1.4).
Asthma-related morbidity was substantial with 26.7% of identified children
hospitalized for asthma and 54.5% with an emergency department visit during their
lifetime. The majority of children (46.4%) were treated with intermittent, quick
relief medications (beta-agonists) alone, whereas only 6.1% were on daily, long
term controller medications. CONCLUSIONS: Asthma screening through a Head Start
program provides an effective means of targeting preschool-aged children from
socioeconomic groups at high risk for asthma. Identification of children early in
the disease course and those at high risk for asthma provides an ideal
opportunity for the implementation of preventive and therapeutic interventions.
PMID- 9651418
TI - Maternal asthma and transient tachypnea of the newborn.
AB - OBJECTIVE: To examine the relationship between transient tachypnea of the newborn
and asthma complicating pregnancy. DESIGN: Historical cohort analysis. Setting.
Singleton live deliveries in New Jersey hospitals during 1989 to 1992 (n = 447
963). PATIENTS: Mother-infant dyads were identified from linked birth certificate
and maternal and infant hospital claims data. Women with an International
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
diagnosis code (493) for asthma (n = 2289) were compared with a four-fold larger
randomly selected control sample (n = 9156) from the remaining pool of women.
MAIN OUTCOME MEASURE: Transient tachypnea of the newborn. RESULTS: In the overall
sample, after controlling for the confounding effects of important variables,
infants of asthmatic mothers were more likely [odds ratio (OR), 1. 79; 95%
confidence interval (CI), 1.35-2.37] than infants of control mothers to exhibit
transient tachypnea of the newborn. A stratified analysis by gestational age and
sex revealed larger and statistically significant associations in term infants
(OR, 2.02; 95% CI, 1.42-2.87) as opposed to preterm infants (OR, 1.51; 95% CI,
0.94-2.43) and in male infants (OR, 1.91; 95% CI, 1.35-2.71) as opposed to female
infants (OR, 1.51; 95% CI, 0.92-2.47). On the other hand, after adjusting for
important confounding variables, respiratory distress syndrome and maternal
asthma were not found to be associated (OR, 1.14; 95% CI, 0.79-1.64). CONCLUSION:
The results of this study provide evidence that maternal asthma is a risk factor
for transient tachypnea of the newborn and differences in gestational age and sex
were apparent in this association. The mechanism for this association remains to
be determined.
PMID- 9651419
TI - Upstairs downstairs: vertical integration of a pediatric service.
AB - BACKGROUND: The combined effects of recent changes in health care financing and
training priorities have compelled academic medical centers to develop innovative
structures to maintain service commitments yet conform to health care marketplace
demands. In 1992, a municipal hospital in the Bronx, New York, affiliated with a
major academic medical center reorganized its pediatric service into a vertically
integrated system of four interdependent practice teams that provided
comprehensive care in the ambulatory as well as inpatient settings. One of the
goals of the new system was to conserve inpatient resources. OBJECTIVE: To
describe the development of a new vertically integrated pediatric service at an
inner-city municipal hospital and to test whether its adoption was associated
with the use of fewer inpatient resources. DESIGN: A descriptive analysis of the
rationale, goals, implementation strategies, and structure of the vertically
integrated pediatric service combined with a before-and-after comparison of in
hospital resource consumption. METHODS: A before-and-after comparison was
conducted for two periods: the period before vertical integration, from January
1989 to December 1991, and the period after the adoption of vertical integration,
from July 1992 to December 1994. Four measures of inpatient resource use were
compared after adjustment for case mix index: mean certified length of stay per
case, mean number of radiologic tests per case, mean number of ancillary tests
per case, and mean number of laboratory tests per case. Difference-in-differences
in-differences estimators were used to control for institution-wide trends
throughout the time period and regional trends in inpatient pediatric practice
occurring across institutions. Results. In 1992, the Department of Pediatrics at
the Albert Einstein College of Medicine reorganized the pediatric service at
Jacobi Medical Center, one of its principal municipal hospital affiliates, into a
vertically integrated pediatric service that combines ambulatory and inpatient
activities into four interdependent practice teams composed of attending
pediatricians, allied health professionals, house officers, and social workers.
The new vertically integrated service was designed to improve continuity of care
for patients, provide a model of practice for professional trainees, conserve
scarce resources, and create a clinical research infrastructure. The vertically
integrated pediatric service augmented the role of attending pediatricians,
extended the use of allied health professionals from the ambulatory to the
inpatient sites, established interdisciplinary practice teams that unified the
care of pediatric patients and their families, and used less inpatient resources.
Controlling for trends within the study institution and trends in the practice of
pediatrics across institutions throughout the time period, the vertical
integration was associated with a decline in 0.6 days per case, the use of 0.62
fewer radiologic tests per case, 0.21 fewer ancillary tests per case, and 2.68
fewer laboratory tests per case. CONCLUSIONS: We conclude that vertical
integration of a pediatric service at an inner-city municipal hospital is
achievable; conveys advantages of improved continuity of care, enhanced
opportunities for primary care training, and increased participation of senior
clinicians; and has the potential to conserve significant amounts of inpatient
resources.
PMID- 9651420
TI - Consequences of the delayed diagnosis of ataxia-telangiectasia.
AB - OBJECTIVES: Ataxia-telangiectasia (AT) is a rare, autosomal recessive
neurodegenerative disorder in which the diagnosis is obvious when ataxia and
telangiectasia are both present. However, the diagnosis can be made upon the
onset of ataxia and before the appearance of telangiectasia if confirmed by
laboratory tests. Early diagnosis is important for genetic counseling,
appropriate care, and avoidance of unnecessary tests. The purpose of this study
is to identify factors responsible for delays in the diagnosis of AT. DESIGN: The
records of all patients seen at the Ataxia-Telangiectasia Clinical Center from
July 1, 1995 to April 1, 1997 were reviewed to determine age of onset of gait
abnormality, recognition of telangiectasia, and diagnosis. RESULTS: In 48
patients with AT, who were the index cases in their respective families, the
median age of diagnosis (78 months) occurred after the onset of gait
abnormalities (15 months) and closely corresponded to the development of
telangiectasia (72 months). In the majority of cases (34/48), telangiectasia
appeared before the diagnosis was established. The most common misdiagnosis was
cerebral palsy (29/48 cases). Twenty-one children (4 with AT) were born after the
start of symptoms in the index case, but before the establishment of a diagnosis.
CONCLUSIONS: The term AT, although a concise and memorable label for the
disorder, is also a barrier to early diagnosis. We recommend the use of routine
serum alpha-fetoprotein testing for all children with persistent ataxia.
PMID- 9651421
TI - A phase I/II study of the protease inhibitor indinavir in children with HIV
infection.
AB - BACKGROUND: Indinavir, an inhibitor of the human immunodeficiency virus type 1
(HIV-1) protease, is approved for the treatment of HIV infection in adults when
antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic
profile of the indinavir free-base liquid suspension and the sulfate salt dry
filled capsules in HIV-infected children, and studied its preliminary antiviral
and clinical activity in this patient population. In addition, we evaluated the
pharmacokinetic profile of a jet-milled suspension after a single dose. METHODS:
Previously untreated children or patients with progressive HIV disease despite
antiretroviral therapy or with treatment-associated toxicity were eligible for
this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per
dose given orally every 8 h) were evaluated in 2 age groups (<12 years and >/=12
years). Indinavir was initially administered as monotherapy and then in
combination with zidovudine and lamivudine after 16 weeks. RESULTS: Fifty-four
HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free
base suspension was less bioavailable than the dry-filled capsule formulation,
and therapy was changed to capsules in all children. Hematuria was the most
common side effect, occurring in 7 (13%) children, and associated with
nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and
zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks
of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose
levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way,
but increased toward baseline after a few weeks of indinavir monotherapy.
CONCLUSIONS: Indinavir dry-filled capsules are relatively well tolerated by
children with HIV infection, although hematuria occurs at higher doses. Future
studies need to evaluate the efficacy of indinavir when combined de novo with
zidovudine and lamivudine.
PMID- 9651422
TI - Family burden and adaptation during the initial year after traumatic brain injury
in children.
AB - OBJECTIVE: Traumatic brain injury (TBI) often leads to long-term behavioral and
cognitive deficits in children. However, little is known about the burden and
psychosocial morbidity of pediatric TBI for families. The purpose of this study
was to test the hypothesis that moderate and severe TBI in children has more
adverse consequences than orthopedic trauma. DESIGN: The sample was comprised of
children between the ages of 6 and 12 recruited from hospital trauma and
inpatient units including 53 with severe TBI, 56 with moderate TBI, and 80 with
orthopedic injuries not involving central nervous system insult. Measures of
injury-related burden, parental distress, and family functioning were
administered to the child's primary caregiver at baseline assessment conducted
soon after injury and at 6- and 12-month follow-ups. Multivariate repeated
measures analysis of covariance was used to examine group differences in these
outcomes over time. RESULTS: Caregivers in the severe TBI group reported
significantly higher levels of family burden, injury-related stress, and parental
psychological symptoms than caregivers in the orthopedic injury group (ORTHO).
The groups did not differ with respect to marital distress. Caregivers in the
severe TBI group were significantly more likely than caregivers in the ORTHO
group to exceed the clinical cutoff on the Brief Symptom Inventory and to report
clinically significant levels of family dysfunction at follow-up. CONCLUSIONS:
The findings suggest that severe TBI is a source of considerable caregiver
morbidity, even when compared with other traumatic injuries. Caregivers in the
severe TBI group had persistent stress associated with the child's injury, as
well as the reactions of other family members, and a relative risk of clinically
significant psychological symptoms nearly twice that of the ORTHO comparison
group. These findings underscore the need for interventions that facilitate
family adaptation after pediatric TBI.
PMID- 9651423
TI - An epidemiologic profile of children with special health care needs.
AB - OBJECTIVE: To present an epidemiologic profile of children with special health
care needs using a new definition of the population developed by the federal
Maternal and Child Health Bureau. METHODS: We operationalized the new definition
using the recently released 1994 National Health Interview Survey on Disability.
Estimates are based on 30 032 completed interviews for children <18 years old.
The overall response rate was 87%. RESULTS: Eighteen percent of US children <18
years old in 1994, or 12.6 million children nationally, had a chronic physical,
developmental, behavioral, or emotional condition and required health and related
services of a type or amount beyond that required by children generally. This
estimate includes children with existing special health care needs but excludes
the at-risk population. Prevalence was higher for older children, boys, African
Americans, and children from low-income and single-parent households. Children
with existing special health care needs had three times as many bed days and
school absence days as other children. An estimated 11% of children with existing
special health care needs were uninsured, 6% were without a usual source of
health care, 18% were reported as dissatisfied with one or more aspects of care
received at their usual source of care, and 13% had one or more unmet health
needs in the past year. CONCLUSIONS: A substantial minority of US children were
identified as having an existing special health care need using national survey
data. Children with existing special health care needs are disproportionately
poor and socially disadvantaged. Moreover, many of these children face
significant barriers to health care.
PMID- 9651424
TI - Neonatal circumcision: when can infants reliably be expected to void?
AB - OBJECTIVE: Analysis of factors influencing voiding after neonatal circumcision.
DESIGN: Prospective study of the following factors in 200 circumcised infants:
birth weight, gestational and postnatal age, type and timing of feeding before
the procedure, and timing of last voiding before circumcision. RESULTS: There was
no significant difference in the age when circumcision was performed between
breastfed infants (6 and 60 hours) and in those formula-fed (8 and 130 hours).
All infants voided after circumcision, with 75% of breastfed infants and 100% of
formula-fed infants voiding within 8 hours of the procedure. Breastfed infants
voided up to 8 hours after the procedure, compared with up to 6 hours in formula
fed infants, but without a significant difference. The interval between last feed
before the procedure and the time of voiding after circumcision was significantly
shorter in formula-fed infants (1 to 9 hours) than in breastfed infants (2 to 21
hours). The interval between precircumcision and postcircumcision voiding was
also significantly shorter in formula-fed infants (3 to 12 hours) than in
breastfed infants (1 to 23 hours). Ninety percent of formula-fed and 64% of
breastfed infants voided within 10 hours of the last voiding before circumcision.
No infants aspirated during the procedure, regardless of the time of the last
feed. No hemorrhagic, infectious, or surgical complications of circumcision were
observed. CONCLUSION: Postoperative voiding time is predictable. Healthy infants
who undergo an uncomplicated circumcision can be discharged before voiding
occurs.
PMID- 9651425
TI - Female genital mutilation. American Academy of Pediatrics. Committee on
Bioethics.
AB - The traditional custom of ritual cutting and alteration of the genitalia of
female infants, girls, and adolescents, referred to as female genital mutilation
(FGM), persists primarily in Africa and among certain communities in the Middle
East and Asia. Immigrants in the United States from areas where FGM is endemic
may have daughters who have undergone a ritual genital procedure or may request
that such a procedure be performed by a physician. The American Academy of
Pediatrics (AAP) believes that pediatricians and pediatric surgical specialists
should be aware that this practice has serious, life-threatening health risks for
children and women. The AAP opposes all forms of FGM, counsels its members not to
perform such ritual procedures, and encourages the development of community
educational programs for immigrant populations.
PMID- 9651426
TI - The psychotherapeutic role of the pediatrician, by Milton J. E. Senn, MD,
Pediatrics, 1948;2:147-152.
PMID- 9651427
TI - Replacement transfusion as a treatment of erythroblastosis fetalis, by Louis K.
Diamond, MD, Pediatrics, 1948;2:520-524.
PMID- 9651428
TI - New concepts of the etiology, diagnosis, and treatment of congenital megacolon
(Hirschsprung's disease), by Orvar Swenson, MD, et al, Pediatrics, 1949;4:201
209.
PMID- 9651429
TI - Humoral antibody formation in infants aged one to three months injected with a
triple (diphtheria-tetanus-pertussis) alum-precipitated antigen, by William L.
Bradford, MD, et al, Pediatrics, 1949;4:711-718.
PMID- 9651430
TI - Treatment of mixed tumors of the kidney in childhood, by Robert E. Gross, MD, and
Edward B. D. Neuhauser, MD, Pediatrics, 1950;6:843-852.
PMID- 9651431
TI - Pseudomonas aeruginosa infection as a complication of therapy in pancreatic
fibrosis (mucoviscidosis), by Sterling D. Garrard, et al, Pediatrics, 1951;8:482.
PMID- 9651432
TI - Agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9:722-728.
PMID- 9651433
TI - Further studies on the treatment of congenital adrenal hyperplasia with
cortisone: IV. Effect of cortisone and compound B in infants with disturbed
electrolyte metabolism, by John F. Crigler Jr, MD, Samuel H. Silverman, MD, and
Lawson Wilkins, MD, Pediatrics, 1952;10:397-413.
PMID- 9651434
TI - A difference in mortality rate and incidence of kernicterus among premature
infants allotted to two prophylactic antibacterial regimens, by William A.
Silverman, et al, Pediatrics, 1956;18:614-624.
PMID- 9651435
TI - The exposure of children to lead, by J. Julian Chisholm and Harold E. Harrison,
Pediatrics, 1956:18;943-958.
PMID- 9651436
TI - The maintenance need for water in parenteral fluid therapy, by Malcolm A.
Holliday, MD, and William E. Segar, MD, Pediatrics, 1957;19:823-832.
PMID- 9651437
TI - Test for the concentration of electrolytes in cystic fibrosis of the pancreas
utilizing pilocarpine by iontophoresis, by Lewis E. Gibson and Robert E. Cooke,
Pediatrics; 1959;24:545-549.
PMID- 9651438
TI - Isolation of the respiratory syncytial virus from a patient with pneumonia, by
Daniel S. Rowe, MD, and Richard H. Michaels, MD, Pediatrics, 1960;26:623-629.
PMID- 9651439
TI - The alveolar lining layer: a review of studies on its role in pulmonary mechanics
and in the pathogenesis of atelectasis, by Mary Ellen Avery, MD, Pediatrics,
1962:30:324-330.
PMID- 9651440
TI - A simple phenylalanine method for detecting phenylketonuria in large populations
of newborn infants, by Robert Guthrie and Ada Susi, Pediatrics, 1963;32:318-343.
PMID- 9651441
TI - Intrauterine growth as estimated from liveborn birth-weight data at 24 to 42
weeks of gestation, by Lula O. Lubchenco et al, Pediatrics, 1963;32:793-800.
PMID- 9651442
TI - Reactions to the threatened loss of a child: a vulnerable child syndrome, by
Morris Green, MD, and Albert A. Solnit, MD, Pediatrics, 1964;34:58-66.
PMID- 9651443
TI - Studies in acute iron poisoning. I. Desferrioxamine In the treatment of acute
iron poisoning: clinical observations, experimental studies, and theoretical
considerations, by Charles F. Whitten et al, Pediatrics, 1965;36:322-335; and
Studies in acute iron poisoning. II. Further observations on desferrioxamine in
the treatment of acute experimental iron poisoning, by Charles F. Whitten et al,
Pediatrics, 1966;38:102-110.
PMID- 9651444
TI - Child development: a basic science for pediatrics, by Julius B. Richmond, MD,
Pediatrics, 1967;39:649-658.
PMID- 9651445
TI - A program to increase health care for children: the pediatric nurse practitioner
program, by Henry K. Silver, MD, Loretta C. Ford, EdD, and Susan G. Stearly, MS,
Pediatrics, 1967;39:756-760.
PMID- 9651446
TI - Antenatal detection of hereditary disorders, by Henry L. Nadler, MD, Pediatrics,
1968;42:912-918.
PMID- 9651447
TI - A controlled trial of antepartum glucocorticoid treatment for prevention of the
respiratory distress syndrome in premature infants, by G. C. Liggins, MB, PhD,
FRCOG, and R. N. Howie, MB, MRACP, Pediatrics, 1972;50:515-525.
PMID- 9651448
TI - Responses of children immunized with capsular polysaccharide of Hemophilus
influenzae type b, by David H. Smith, MD, et al, Pediatrics, 1973;52:637-644; and
Haemophilus influenzae type b capsular polysaccharide vaccine in children: a
double-blind field study of 100 000 vaccinees 3 months to 5 years of age in
Finland, by Heikki Peltola, MD et al, Pediatrics, 1977;60:730-737.
PMID- 9651449
TI - Tap water scald burns in children, by K. W. Feldman, R. T. Schaller, J. A.
Feldman, and M. McMillon, Pediatrics, 1978;62:1-7.
PMID- 9651450
TI - Report of the New England Regional Infant Cardiac Program, by Donald C. Fyler,
MD, Pediatrics, 1980;65(suppl):375-461.
PMID- 9651451
TI - Apgar scores as predictors of chronic neurologic disability, by Karin B. Nelson,
MD, and Jonas H. Ellenberg, PhD, Pediatrics, 1981;68:36-44.
PMID- 9651452
TI - Aerosol beclomethasone dipropionate compared with theophylline as primary
treatment of chronic, mild to moderately severe asthma in children, by David G.
Tinkelman, MD, et al, Pediatrics, 1993;92:64-77.
PMID- 9651453
TI - Resuscitation of asphyxiated newborn infants with room air or oxygen: an
international controlled trial: the Resair 2 study.
AB - OBJECTIVE: Birth asphyxia represents a serious problem worldwide, resulting in
approximately 1 million deaths and an equal number of serious sequelae annually.
It is therefore important to develop new and better ways to treat asphyxia.
Resuscitation after birth asphyxia traditionally has been carried out with 100%
oxygen, and most guidelines and textbooks recommend this; however, the scientific
background for this has never been established. On the contrary, theoretic
considerations indicate that resuscitation with high oxygen concentrations could
have detrimental effects. We have performed a series of animal studies as well as
one pilot study indicating that resuscitation can be performed with room air just
as efficiently as with 100% oxygen. To test this more thoroughly, we organized a
multicenter study and hypothesized that room air is superior to 100% oxygen when
asphyxiated newborn infants are resuscitated. METHODOLOGY: In a prospective,
international, controlled multicenter study including 11 centers from six
countries, asphyxiated newborn infants with birth weight >999 g were allocated to
resuscitation with either room air or 100% oxygen. The study was not blinded, and
the patients were allocated to one of the two treatment groups according to date
of birth. Those born on even dates were resuscitated with room air and those born
on odd dates with 100% oxygen. Informed consent was not obtained until after the
initial resuscitation, an arrangement in agreement with the new proposal of the
US Food and Drug Administration's rules governing investigational drugs and
medical devices to permit clinical research on emergency care without the consent
of subjects. The protocol was approved by the ethical committees at each
participating center. Entry criterion was apnea or gasping with heart rate <80
beats per minute at birth necessitating resuscitation. Exclusion criteria were
birth weight <1000 g, lethal anomalies, hydrops, cyanotic congenital heart
defects, and stillbirths. Primary outcome measures were death within 1 week
and/or presence of hypoxic-ischemic encephalopathy, grade II or III, according to
a modification of Sarnat and Sarnat. Secondary outcome measures were Apgar score
at 5 minutes, heart rate at 90 seconds, time to first breath, time to first cry,
duration of resuscitation, arterial blood gases and acid base status at 10 and 30
minutes of age, and abnormal neurologic examination at 4 weeks. The existing
routines for resuscitation in each participating unit were followed, and the
ventilation techniques described by the American Heart Association were used as
guidelines aiming at a frequency of manual ventilation of 40 to 60 breaths per
minute. RESULTS: Forms for 703 enrolled infants from 11 centers were received by
the steering committee. All 94 patients from one of the centers were excluded
because of violation of the inclusion criteria in 86 of these. Therefore, the
final number of infants enrolled in the study was 609 (from 10 centers), with 288
in the room air group and 321 in the oxygen group. Median (5 to 95 percentile)
gestational ages were 38 (32.0 to 42.0) and 38 (31.1 to 41.5) weeks (NS), and
birth weights were 2600 (1320 to 4078) g and 2560 (1303 to 3900) g (NS) in the
room air and oxygen groups, respectively. There were 46% girls in the room air
and 41% in the oxygen group (NS). Mortality in the first 7 days of life was 12.2%
and 15.0% in the room air and oxygen groups, respectively; adjusted odds ratio
(OR) = 0.82 with 95% confidence intervals (CI) = 0.50-1.35. Neonatal mortality
was 13.9% and 19.0%; adjusted OR = 0. 72 with 95% CI = 0.45-1.15. Death within 7
days of life and/or moderate or severe hypoxic-ischemic encephalopathy (primary
outcome measure) was seen in 21.2% in the room air group and in 23.7% in the
oxygen group; OR = 0.94 with 95% CI = 0.63-1.40. (ABSTRACT TRUNCATED)
PMID- 9651454
TI - Airbag injuries in infants and children: a case report and review of the
literature.
AB - Airbags have saved an estimated 2620 lives as of November 1997. However, airbags
also have caused a number of injuries and deaths and have received a lot of
publicity from the NHTSA and the media as a result. The majority of the injuries
have occurred when seat belts and shoulder harnesses were not used properly in
conjunction with airbags. This article describes an injury that apparently
occurred despite use of an age-appropriate, state-of-the-art child protection
seat.
PMID- 9651455
TI - Reducing risks to children in vehicles with passenger airbags.
AB - This review examines the risk that passenger airbags pose for children and
discusses behavioral and technologic measures aimed at protecting children from
airbag deployment. Although airbags reduce fatal crash injuries among adult
drivers and passengers, this safety technology increases mortality risk among
children younger than age 12. The magnitude of the risk is multiplied when
children are unrestrained or restrained improperly. As new vehicles are resold to
buyers who tend to be less safety-conscious than new car owners, the number of
children endangered by passenger airbag deployment may increase. For vehicles
already in the fleet, strong measures are required to secure children in the rear
seat and increase the proper use of appropriate restraint systems through police
enforcement of laws. One promising strategy is to amend child passenger safety
laws to require that parents secure children in the rear seats. For future
vehicles, a mandatory performance standard should be adopted that suppresses
airbag deployment automatically if a child is located in the front passenger
seat. Other promising improvements in airbag design also are discussed. Major
changes in passenger airbag design must be evaluated in a broad analytical
framework that considers the welfare of adults as well as children.
PMID- 9651456
TI - Childhood obesity, adipose tissue distribution, and the pediatric practitioner.
AB - The prevalence of pediatric obesity is increasing in the United States. Sequelae
from pediatric obesity are increasingly being seen, and long-term complications
can be anticipated. Obesity is the most common cause of abnormal growth
acceleration in childhood. Obesity in females is associated with an early onset
of puberty and early menarche. Puberty is now occurring earlier in females than
in the past, and this is probably related either directly or indirectly to the
population increase in body weight. The effect of obesity on male pubertal
maturation is more variable, and obesity can lead to both early and delayed
puberty. Pubertal gynecomastia is a common problem in the obese male. Many of the
complications of obesity seen in adults appear to be related to increased
accumulation of visceral fat. It has been proposed that subcutaneous fat may be
protective against the adverse effects of visceral fat. Males typically
accumulate fat in the upper segment of the body, both subcutaneously and
intraabdominally. In females, adiposity is usually subcutaneous and is found
particularly over the thighs, although visceral fat deposition also occurs.
Gender-related patterns of fat deposition become established during puberty and
show significant familial associations. There are no reliable means for assessing
childhood and adolescent visceral fat other than radiologically. Noninsulin
dependent diabetes is being seen more commonly in the pediatric population.
Diabetes and impaired glucose tolerance are noted particularly in obese children
with a family history of diabetes. In this situation, a glucose tolerance test
may be indicated, even in the presence of fasting normoglycemia.
Hypertriglyceridemia and low high-density lipoprotein-cholesterol levels are the
primary lipid abnormalities of obesity and are related primarily to the amount of
visceral fat. Low-density lipoprotein-cholesterol levels are not typically
elevated in simple obesity. The offspring of parents with early coronary disease
tend to be obese. Very low-density lipoprotein and intermediate-density
lipoprotein particles, which are small in size, may be important in atherogenesis
but they cannot be identified in a fasting lipid panel. The propensity to
atherogenesis cannot be interpreted readily from a fasting lipid panel, which
therefore should be interpreted in conjunction with a family history for coronary
risk factors. Hypertriglyceridemia may be indicative of increased visceral fat,
familial combined hyperlipidemia, familial dyslipidemic hypertension, impaired
glucose tolerance, or diabetes. Almost half of adult females with polycystic
ovary syndrome are obese and many have a central distribution of body fat. This
condition frequently has its origins in adolescence. It is associated with
increased androgen secretion, hirsutism, menstrual abnormalities, and
infertility, although these may not be present in every case. Adults with
polycystic ovary syndrome adults are hyperlipidemic, have a high incidence of
impaired glucose tolerance and noninsulin-dependent diabetes, and are at
increased risk for coronary artery disease. Weight reduction and lipid lowering
therefore are an important part of therapy. Obstructive sleep apnea with daytime
somnolence is a common problem in obese adults. Pediatric studies suggest that
obstructive sleep apnea occurs in approximately 17% of obese children and
adolescents. Sleep disorders in the obese may be a major cause of learning
disability and school failure, although this remains to be confirmed. Symptoms
suggestive of a sleep disorder include snoring, restlessness at night with
difficulty breathing, arousals and sweating, nocturnal enuresis, and daytime
somnolence. Questions to exclude obstructive sleep apnea should be part of the
history of all obese children, particularly for the morbidly obese. For many
children and adolescents with mild obesity, and particularly for females, one can
speculate that obesity may not be a great health risk
PMID- 9651458
TI - Clinical features of acute allergic reactions to peanut and tree nuts in
children.
AB - BACKGROUND: Peanut (PN) and tree nut (TN) allergies are potentially life
threatening, rarely outgrown, and appear to be increasing in prevalence. However,
there is relatively little reported about the clinical features of acute
reactions to these foods and their potential association. OBJECTIVE: To describe
the clinical features of acute reactions during initial and subsequent accidental
ingestions of PN and TN among children with a history of at least one acute
allergic reaction to these foods. DESIGN: Questionnaire survey, examination, and
serologic testing for specific IgE antibody of patients with convincing histories
of acute reactions (at least one organ system involved within 60 minutes of
ingestion) to PN or TN. RESULTS: A total of 122 patients (63% males; median age,
8 years at time of study) had acute reactions; 68 had reactions only to PN, 20
only to TN, and 34 to both PN and TN. Of those reacting to TN, 34 had reactions
to one, 12 to two, and 8 to three or more different TN, the most common being
walnut, almond, and pecan. Initial reactions usually occurred at home (median
age, 24 months for PN and 62 months for TN) and were considered to result from a
first exposure in 72% of cases. Eighty-nine percent of the reactions involved the
skin (urticaria, angioedema), 52% the respiratory tract (wheezing, throat
tightness, repetitive coughing, dyspnea), and 32% the gastrointestinal tract
(vomiting, diarrhea). Two organ systems were affected in 31% of initial
reactions, and all three in 21% of reactions. Thirty-eight of 190 first reactions
to PN or TN were treated with epinephrine. Accidental ingestions occurred in 55%
of PN-allergic children (average of two accidents per patient with an accidental
ingestion) and in 30% of TN-allergic children over a median period of 5.5 years.
On average, symptoms after accidental exposure were generally similar to those at
initial exposure. Accidents occurred commonly in school but also at home and in
restaurants. Modes of accidental ingestion included sharing food, hidden
ingredients, cross-contamination, and school craft projects using peanut butter.
Eighty-three percent of the children were breastfed, with >90% of the mothers
ingesting PN and at least one TN during lactation. Among patients reporting no
history of exposure (>60% of patients for each TN), IgE antibodies were found to
a particular TN in 50% to 82% of patients and to PN in 100% of patients.
CONCLUSIONS: Acute allergic reactions to PN occur early in life. PN and TN
allergic reactions coexist in one third of PN-allergic patients, frequently occur
on first known exposure, and may be life-threatening, requiring emergency
treatment. Accidental ingestions are common, occur frequently outside of the
home, and often require emergency treatment. Consequently, early diagnosis
followed by education on avoidance and treatment measures (including self
administered epinephrine) is imperative.
PMID- 9651457
TI - Incidence of passive exposure to crack/cocaine and clinical findings in infants
seen in an outpatient service.
AB - OBJECTIVES: Passive exposure to crack/cocaine and the associated clinical
symptoms may present a significant health risk to very young infants and
children. This study was designed to determine the incidence of cocaine exposure,
presumed to be passive, in ill infants younger than 1 year of age, using a
threshold of detection for cocaine and/or its major metabolite, benzoylecognine
(BE), that is lower than the current National Institute on Drug Abuse standard.
The study also investigates the morbidity associated with passive cocaine
exposure in this population. METHODS: We prospectively obtained 124 samples of
urine from 122 children younger than 1 year of age for routine clinical
indications from the emergency department at Yale-New Haven Hospital. Samples
were analyzed by radioimmunoassay (RIA) for cocaine, with cross-reactivity for
BE. The presence of BE in a portion of the RIA-positive samples also was detected
in additional analyses by enzyme-multiplied immunoassay technique or by gas
chromatography-mass spectrometry. A chart review was conducted on all 122
patients by reviewers blind to the urine toxicology results. Presenting
complaints, symptoms, vital signs, and diagnosis were obtained for all visits
before the first birthday. Birth history, including maternal drug history and
birth weight, demographics, and number of medical visits in the first year, were
recorded as well. RESULTS: Of the 124 samples, 45 (36.3%) were positive (>/=50
ng/mL of BE equivalents) for cocaine and/or cocaine metabolite by RIA testing.
The positive results, determined by RIA, were highly correlated with patients who
had lower and upper respiratory symptoms and sought medical care more often.
CONCLUSIONS: The incidence of unsuspected, passive cocaine exposure in ill
infants seeking medical care primarily through an emergency service may be as
high as 1 in 3 to 6 infants from our predominantly inner city population. Current
immunoassay methods, specific for BE, and their routine threshold of detection
(200 to 300 ng/mL) may not be sensitive enough to detect cocaine and BE in the
urine samples of children younger than 1 year of age who are exposed passively.
The development of upper and lower respiratory symptoms is correlated
significantly with positive urine results in this study. The increased use of
health care resources correlated with passive cocaine exposure in this sample may
serve as an indirect marker for the increased medical needs of these infants.
PMID- 9651459
TI - Kawasaki disease in the older child.
AB - OBJECTIVES: To determine the prevalence of Kawasaki disease in older children and
to evaluate its clinical presentation, time to diagnosis, and outcome in
comparison with younger patients with the disease. METHODOLOGY: A retrospective
analysis of all patients discharged with a diagnosis of Kawasaki disease at a
pediatric tertiary care hospital over a 12-year period. RESULTS: A total of 133
patients were included in this study; 7.5% were 9 years of age or older at the
time of illness. Patients were grouped by age: infants included children age 1 to
8 years of age and children 9 years of age or older. Older children had a higher
frequency of abnormal cardiovascular physical examination (50%) versus children
(6%) and infants (10%). The older age group and the infants had a higher
prevalence of coronary artery abnormalities and poor left ventricular function
than did the 1- to 8-year-olds. Eighty percent of the older children had coronary
arteries that were either dilated or aneurysmal, and 30% demonstrated left
ventricular dysfunction on initial echocardiography. The number of days to
diagnosis after meeting the diagnostic criteria was 5.8 +/- 2.3 for infants, 5.2
+/- 1.5 for older children, and 1.9 +/- 0.3 for children. Older children had a
complicated course of Kawasaki disease compared with younger patients.
CONCLUSION: We found a higher prevalence of older children with Kawasaki disease
at our center than has previously been reported. Older patients, as well as
infants, had a higher rate of coronary artery abnormalities than did the children
between 1 and 8 years of age. Older age at the time of illness or a delay in
treatment may be important factors in determining cardiac involvement in Kawasaki
disease.
PMID- 9651460
TI - Early language development in children exposed to or infected with human
immunodeficiency virus.
AB - OBJECTIVES: To compare language development in infants and young children with
human immunodeficiency virus (HIV) infection to language development in children
who had been exposed to HIV but were uninfected, and (among subjects with HIV
infection) to compare language development with cognitive and neurologic status.
DESIGN: Prospective evaluation of language development in infected and in exposed
but uninfected infants and young children. SETTING: Pediatric Infectious Disease
Clinic, State University of New York-Health Science Center at Syracuse. SUBJECTS:
Nine infants and young children infected with HIV and 69 seropositive but
uninfected infants and children, age 6 weeks to 45 months. RESULTS: Mean Early
Language Milestone Scale, 2nd edition (ELM-2) Global Language scores were
significantly lower for subjects with HIV infection, compared with uninfected
subjects (89.3 vs 96.2, Mann-Whitney U test). The proportion of subjects scoring
>2 SD below the mean on the ELM-2 on at least one occasion also was significantly
greater for subjects with HIV infection, compared with uninfected subjects (4 of
9 infected subjects, but only 5 of 69 uninfected subjects; Fisher's exact test).
Seven of the 9 subjects with HIV infection manifested deterioration of language
function. Four manifested unremitting deterioration; only 1 of these 4
demonstrated unequivocal abnormality on neurologic examination. Three subjects
with HIV infection and language deterioration showed improvement in language
almost immediately after the initiation of antiretroviral drug treatment.
Magnetic resonance imaging or computed tomography of the brain were performed in
6 of 7 infected subjects with language deterioration, and findings were normal in
all 6. ELM-2 Global Language scaled scores showed good agreement with the Bayley
Mental Developmental Index or the McCarthy Global Cognitive Index (r = 0. 70).
Language deterioration, or improvement in language after initiation of drug
therapy, coincided with or preceded changes in global cognitive function, at
times by intervals of up to 12 months. CONCLUSIONS: Language deterioration occurs
commonly in infants and young children with HIV infection, is seen frequently in
the absence of abnormalities on neurologic examination or central nervous system
imaging, and may precede evidence of deterioration in global cognitive ability.
Periodic assessment of language development should be added to the developmental
monitoring of infants and young children with HIV infection as a means of
monitoring disease progression and the efficacy of drug treatment.
PMID- 9651461
TI - Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months,
and a psychosexual follow-up in young adulthood.
AB - Guidelines of psychosexual management for infants born with physical intersex
conditions are intended to assist physicians and parents in making decisions
about sex of assignment and rearing including the following: 1) sex assignment
should be to the gender that carries the best prognosis for good reproductive
function, good sexual function, normal-looking external genitalia and physical
appearance, and a stable gender identity; 2) the decision regarding sex
assignment should be made as early as possible, preferably during the newborn
period, with an upper age limit for reversal of an initial sex assignment no
later than 18 to 24 months; and 3) there should be minimal uncertainty and
ambiguity on the part of parents and professionals regarding the final decision
about sex assignment and rearing. J. Money used these guidelines in a case of a
biologically normal male infant (one of a pair of monozygotic twins) whose penis
was accidentally ablated during a circumcision at the age of 7 months. The
decision to reassign the infant boy to the female sex and to rear him as a girl
was made at 17 months, with surgical castration and initial genital
reconstruction occurring at 21 months. Money reported follow-up data on this
child through the age of 9 years. Although the girl was described as having many
"tomboyish" behavioral traits, a female gender identity had apparently
differentiated. Thus, it was concluded that gender identity is sufficiently
incompletely differentiated at birth as to permit successful assignment of a
genetic male as a girl, in keeping with the experiences of rearing. Subsequent
follow-up by other investigators reported that by early adolescence the patient
had rejected the female identity and began to live as a male at the age of 14
years. In adulthood, the patient recalled that he had never felt comfortable as a
girl, and his mother reported similar recollections. At age 25, the patient
married a woman and adopted her children. The patient reported exclusive sexual
attraction to females. The present case report is a long-term psychosexual follow
up on a second case of ablatio penis in a 46 XY male. During an electrocautery
circumcision at the age of 2 months, the patient sustained a burn of the skin of
the entire penile shaft, and the penis eventually sloughed off. At age 7 months,
the remainder of the penis and the testes were removed. By age 7 months, if not
earlier, the decision was made to reassign the patient as a female and to raise
the infant as a girl. The patient was interviewed on two occasions: at 16 years
and twice while in the hospital for additional surgery at 26 years of age. At
ages 16 and 26, the patient was living socially as a woman and denied any
uncertainty about being a female. During childhood, the patient recalled that she
self-identified as a "tomboy" and enjoyed stereotypically masculine toys and
games; however, the patient also recalled that her favorite playmates were
usually girls and that her best friend was always a girl. When seen at age 16,
the patient had been admitted to the hospital for vaginoplasty. At that time, she
wished to proceed with the further repair of her genitalia to make them suitable
for sexual intercourse with males. At age 26, the patient returned to the
hospital for further vaginoplasty. Regarding the patient's sexual orientation,
she was attracted predominantly to women in fantasy, but had had sexual
experiences with both women and men. At the time of the second surgery, she was
in a relationship with a man and wished to be able to have intercourse. The
patient's self-described sexual identity was "bisexual." After surgery at age 26
years, the patient developed a rectovaginal fistula. Within a few months of the
surgery, the patient and her male partner separated for reasons other than the
patient's physical problems. The patient subsequently began living with a new
partner, a woman, in a lesbian relationship. The psychosexual development of our
patient was bot the other patient was married to a woman. Our patient had a
"bisexual" sexual identity; the other patient had a "heterosexual" sexual
identity. The patients were similar in that they had a childhood history of
"tomboyism." Our patient was predominantly sexually attracted to women; the other
patient was exclusively sexually attracted to women. Our patient had sexual
experiences with both women and men; the other patient had sexual experiences
only with women. The most plausible explanation of our patient's differentiation
of a female gender identity is that sex of rearing as a female, beginning at
around age 7 months, overrode any putative influences of a normal prenatal
masculine sexual biology. Because cases of ablatio penis in infancy are so rare
and long-term follow-up data are scant, it is obviously impossible to know
whether our patient or the previous case would be more typical of the
psychosexual outcome in a larger sample of such individuals. However, our case
suggests that it is possible for a female gender identity to differentiate in a
biologically "normal" genetic male. At present, however, the clinical literature
is deeply divided on the best way to manage cases of traumatic loss of the penis
during infancy. Further study is clearly required to decide on the optimal model
of psychosocial and psychosexual management for affected individuals.
PMID- 9651462
TI - A comparison of supination/flexion to hyperpronation in the reduction of radial
head subluxations.
AB - OBJECTIVE: To compare supination at the wrist followed by flexion at the elbow
(the traditional reduction technique) to hyperpronation at the wrist in the
reduction of radial head subluxations (nursemaid's elbow). MATERIALS AND METHODS:
This prospective, randomized study involved a consecutive sampling of children
younger than 6 years of age who presented to one of two urban pediatric emergency
departments and two suburban pediatric ambulatory care centers with a clinical
diagnosis of radial head subluxation. Patients were randomized to undergo
reduction by one of the two methods and were followed every 5 minutes for return
of elbow function. The initial procedure was repeated if baseline functioning did
not return 15 minutes after the initial reduction attempt. Failure of that
technique 30 minutes after the initial reduction attempt resulted in a cross-over
to the alternate method of reduction. The alternate procedure was repeated if
baseline functioning did not return 15 minutes after the alternate procedure was
attempted. If the patient failed both techniques, radiography of the elbow was
performed. RESULTS: A total of 90 patients were enrolled in the study. Five
patients were removed from further analysis secondary to a final diagnosis of
fracture, 84 were reduced successfully, and 1 failed both techniques. Demographic
characteristics of each group were similar. Thirty-nine of 41 patients (95%)
randomized to hyper-pronation were reduced successfully on the first attempt
versus 34 of 44 patients (77%) randomized to supination. Two patients in the
hyperpronation group required two attempts versus 10 patients in the supination
group. Hyperpronation was more successful; 40 of 41 patients (97.5%) in the
hyperpronation group were reduced successfully versus 38 of 44 patients (86%) in
the supination group. Of the 6 patients who crossed over from supination to
hyperpronation, 5 were reduced on the first attempt and 1 was reduced on the
second attempt. CONCLUSIONS: In the reduction of radial head subluxations, the
hyperpronation technique required fewer attempts at reduction compared with
supination, was successful more often than supination, and was often successful
when supination failed.
PMID- 9651463
TI - Maternal cigarette smoking and child psychiatric morbidity: a longitudinal study.
AB - OBJECTIVE: Previous studies have linked maternal smoking during pregnancy with
behavioral disturbance in children. However, additional evidence is needed to
address the causality of the relationship. The present study analyses result from
an Australian cohort of 5342 5-year-old children whose mothers were recruited
early in pregnancy. METHODS: Smoking history was gathered for prepregnancy, first
clinic visit (FCV), late pregnancy, and when the child was 6 months and 5 years
of age. Behavior problems at the age of 5 were assessed using a modified Child
Behavior Check List (CBCL) shown to have high agreement with the complete CBCL.
This resulted in the formation of three scales: internalizing; social,
attentional and thought; and externalizing behavior problems, which were then
dichotimized at the 90th percentile in each case. Logistic regression was used to
model these outcomes as a function of maternal smoking at five time points during
which it was assessed. A series of models explored the effect of additional
adjustment for confounding. The predictors of attrition (29.5%) throughout the
cohort were also identified by multivariate modeling. RESULTS: The final analysis
was carried out on a cohort of mother-child pairs for whom data and child
behavior outcomes were complete. The mean age of children was 5 years, 6 months
with a range from 4 to 6 years. The mean age of mothers at the time of birth of
the child was 25 years, with a range from 13 to 47 years. Mothers lost to follow
up were more likely to be younger, single, and less well-educated than those who
continued participation, although maternal smoking was not an independent
determinant. Unadjusted analyses showed strong associations between externalizing
child behavior and maternal smoking during pregnancy and at the 5-year follow-up,
with relative risks (RRs) up to 2.6 for children of women smoking at least 20
cigarettes per day at the first antenatal clinic visit. A clear dose-response
relationship existed in most relationships with higher levels of smoking being
associated with higher rates of externalizing behavior problems. Weaker
relationships occurred for internalizing behavior and social, attentional and
thought behavior problems. Multivariate analysis of the timing in more detail
that the association between maternal smoking and child behavior problems
persisted, although the evidence for dose-response diminished. Moreover, it was
primarily associated with smoking as determined by questions asked at the FCV (RR
= 1.52, 2.03, 2.16) for 1 to 9, 10 to 19, and >/=20 cigarettes per day,
respectively, compared with nonsmoking and secondarily by smoking determined at
the 5-year follow-up (RR = 1.52, 1.87, 1.29) for 1 to 9, 10 to 19, and >/=20
cigarettes per day respectively, compared with nonsmoking. This association
appeared to be independent of a wide range of possible confounders such as
maternal age, education, social class, marital status and mental health,
gestation at FCV, complications during pregnancy, the child's sex, gestational
age at birth, and age at last follow-up. Adjustments were also made for the
mother's employment since birth, family structure, and maternal mental health at
the time of the CBCL assessment. Associations between externalizing behavior
problems and maternal smoking at other times, and those between other behavioral
problems examined and maternal smoking were not significant. CONCLUSION: Although
previous studies have found evidence for an association between maternal smoking
and child behavior problems, the strength of this study lies in its size, its
detailed and consistent measurement of maternal smoking, and its ability to
control for many social and biological factors linked to maternal smoking and
child behavior. (ABSTRACT TRUNCATED)
PMID- 9651464
TI - Further delineation of aortic dilation, dissection, and rupture in patients with
Turner syndrome.
AB - OBJECTIVE: Although cardiovascular malformations (CVMs) are well-recognized
congenital anomalies in Turner syndrome, aortic dilation and dissection are less
common and less familiar. Most of the relevant literature is limited to single
cases reports or small series. We sought to increase the information available
about the frequency and characteristics of aortic dilation in patients with
Turner syndrome. DESIGN: A 1-page survey of cardiac abnormalities, including
aortic dilation, was mailed to approximately 1000 (1040 verified) members of the
Turner Syndrome Society as an enclosure in the June 1997 newsletter. We also
conducted a literature review. PARTICIPANTS: A total of 245 patients or families
of patient members of the Turner Syndrome Society responded to the survey (
approximately 24% response rate). RESULTS: A CVM was reported in 120 of 232 (52%)
respondents to this questionnaire. Obstructive lesions of the left side of the
heart predominated and included bicuspid aortic valve (38%) and coarctation
(41%). Aortic dilation was reported in at least 15 of 237 respondents (6.3%; 95%
confidence interval: 3.6%-10.3%); 2 of 15 (13%) had dissection. Twelve of 15
(80%) patients had an associated risk factor for aortic dilation such as a CVM or
hypertension. The 3 (20%) patients who did not have a CVM or hypertension were
all younger than 21 years. In the entire group with aortic dilation, 10 of 15
(67%) patients were younger than 21 years. All patients with aortic dilation had
involvement of the ascending aorta, and 2 had additional involvement of the
descending aorta distal to a repaired coarctation. An update of the literature
revealed 68 patients with aortic dilation, dissection, or rupture. An associated
CVM or hypertension was reported in 53 of 59 (90%) informative patients. At least
6 (10%) had no predisposing risk factor (information was inadequate for 9 of 68
patients). The following patterns of aortic involvement were identified:
ascending +/- descending aorta with coarctation (14); ascending +/- descending
aorta without coarctation (39); descending aorta with coarctation (3); descending
thoracic or abdominal aorta without coarctation (4); and unspecified (8).
Dissection or rupture was reported in 42/68 (62%). Two reported patients died
suddenly from aortic dissection in the third trimester of assisted pregnancy. At
least 20 (29%) patients were younger than 21 years. One of the 6 (17%) patients
with isolated aortic dilation was in this younger group. CONCLUSIONS: More
information is needed about the frequency and natural history of aortic dilation
in Turner syndrome. This work contributes new patient data and increases the
literature review. Despite the well-recognized limitations of self-reporting,
this survey detected aortic dilation with or without dissection in approximately
6% of patients with Turner syndrome. Although rare, this is a potentially
catastrophic occurrence, warranting greater awareness among health professionals.
In this study and the literature, the vast majority of patients with aortic
dilation have an associated risk factor such as a CVM, typically bicuspid aortic
valve or coarctation, or systemic hypertension. These patients represent a higher
risk group that should be followed appropriately, usually under the direction of
a cardiologist. Patients undergoing assisted pregnancy also should be evaluated
closely. It is generally accepted that at the time of diagnosis of Turner
syndrome, all patients should have a complete cardiology evaluation including
echocardiography. The small number of patients with aortic dilation without a
CVM, who would not be under the long-term care of a cardiologist, makes it
prudent to screen all patients with Turner syndrome for this potentially lethal
abnormality. The specific timing for this screening is controversial. Our
recommendations for prospective imaging do not represent a rigid standard of
care.
PMID- 9651465
TI - Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis.
AB - OBJECTIVE: Pancreatic enzyme is essential in the treatment of cystic fibrosis
(CF), but intolerance to it occasionally occurs. We encountered a child who was
intolerant to multiple commercially available preparations of pancreatic enzymes
and, hence, desensitization was attempted, with success. CASE PRESENTATION: A 33
month-old girl was diagnosed with CF at 6 months of age. Initially, she was
started on Pancrease MT 16, which was subsequently discontinued because fecal fat
studies were normal and she seemed to do well on Nutramigen and vitamin
supplements. At 29 months of age, she developed diarrhea with bulky stools and
weight loss. A fecal fat 72-hour study revealed a coefficient of absorption of
50%. She was treated with Pancrease MT 16, but had consistent vomiting 1 to 2
hours after administration of enzymes. The vomiting occurred on switching to
different pancreatic enzymes preparations, ie, Creon 10, Viokase, and Pancrease
MT 16. Vomiting occurred even with small doses of enzymes disguised in food. She
had no history suggestive of gastroesophageal reflux, peptic ulcer, or pork
allergy, and no vomiting on days when enzymes were not given. This was suggestive
of type I hypersensitivity reaction. Pancreatic enzymes were discontinued, and
she was given a low-fat, high-carbohydrate diet with satisfactory weight gain.
METHODS: Double-blind, placebo-controlled titrated oral challenges with
pancreatic enzymes resulted in definite vomiting within 1 to 1.5 hours after
challenges with Viokase and Pancrease MT 16, but not with placebo. Rush oral
desensitization with Viokase solution was attempted, starting with 5 mg, and the
dose was doubled every 20 minutes, aiming to reach a cumulative dose of 700 mg.
However, the child vomited when a cumulative dose of 315 mg was reached. Another
trial of slower desensitization was done using Pancrease MT 16 (1 capsule: 16 000
U of lipase, 48 000 U of amylase, and 48 000 U of protease), starting with 1/4
capsule per day, with increments of 1/4 capsule every 3 days, until an entire
capsule was reached by day 10, then increased by approximately 1/2 capsule every
4 days until reaching the therapeutic dose of 1 capsule with each meal by day 25.
RESULTS: The patient tolerated this fairly well and has been on this treatment
and regular diet for >1 year, without any adverse reaction. This illustrates a
rare case of gastrointestinal adverse reaction to pancreatic enzymes that was
treated successfully with desensitization. CONCLUSION: Pancreatic enzyme
intolerance, although rare, would be a major problem in the management of
patients with CF. Hence, desensitization would be essential and may be
accomplished successfully using the protocol described in this report.
PMID- 9651466
TI - One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for
Helicobacter pylori infection in children and adolescents.
AB - BACKGROUND: Resolution of Helicobacter pylori infection is important in the
management of peptic ulcer disease and reduces peptic ulcer recurrence in both
adults and children. Various anti-H pylori treatment regimens have been proposed,
reflecting the incomplete clinical success of each. A combination of omeprazole,
clarithromycin, and tinidazole, given for 1 week, has been shown to be highly
tolerable and effective, achieving a success rate of >90% in the adult
population. OBJECTIVE: The aim of this study was to evaluate this short-term
regimen in pediatric and adolescent populations. METHODS: The study group
consisted of 35 children referred for evaluation of dyspeptic symptoms. They all
underwent upper gastrointestinal endoscopy, in which H pylori infection was
confirmed by rapid urease test and/or histologic staining. They were given
omeprazole (20 mg twice daily), clarithromycin (250 mg twice daily), and
tinidazole or metronidazole (500 mg twice daily) for 1 week. The patients were
divided into two groups: those who received the first course of anti-H pylori
therapy during this study (group 1) and those who had previously received
standard metronidazole and bismuth combination therapies that failed to eradicate
H pylori (group 2). Therapeutic efficacy was assessed by a 13C-urea breath test
performed 4 weeks after completion of treatment. Results. The 35 study patients
had a mean age of 15.9 years (range, 10 to 19) and included 19 males and 16
females, of whom 22 were born in Israel and 13 were immigrants from the former
USSR. There were 27 patients (77. 1%) in group 1 and 8 patients (22.9%) in group
2. Endoscopic findings were nodular gastritis (14), gastritis (11), gastric ulcer
(1), duodenal ulcer (5), and duodenitis (4). H pylori resolution was
significantly higher in group 1 patients (24/27, 88.9%) than in group 2 patients
(1/8, 12.5%). There was no difference between patients with nodular gastritis and
those with nonnodular gastritis, and between Israeli-born patients and patients
born in the former USSR. Compliance in both groups was equally good, and no major
side effects were recorded. CONCLUSIONS: One-week
omeprazole/clarithromycin/tinidazole triple therapy is highly tolerable and
effective for treating H pylori in the pediatric age group, but previous
treatment failure diminishes the likelihood of success with this regimen.
PMID- 9651467
TI - Voltage-dependent calcium influx in human sperm assessed by simultaneous optical
detection of intracellular calcium and membrane potential.
AB - There are several physiological and pharmacological evidences indicating that
opening of voltage dependent calcium channels play a crucial role in the
induction of the acrosome reaction in mammalian sperm. In mature sperm,
physiological inductors of the acrosome reaction such as ZP3, a zona pellucida
protein, and the steroid hormone progesterone, induce depolarization and calcium
influx, which are required for the acrosome reaction. In this paper, we describe
a voltage-dependent calcium influx present in human sperm. We report an
experimental procedure that allows measurement of intracellular calcium and
membrane potential simultaneously using the fluorescent dyes DiSC3(5) and Fura-2.
We found that in human uncapacitated sperm, depolarization induces a nifedipine
insensitive calcium influx that, in most cases, was transient. Calcium influx was
observed in the range of -60 to -15 mV (the range tested). At resting membrane
potential (around -40 mV), potassium addition depolarized and induced calcium
influx, but when the depolarization was preceded by a hyperpolarization (induced
with valinomycin), calcium influx was remarkably enhanced, suggesting that at -40
mV, channels are in a putative inactivated state. When sperm was incubated in
medium without calcium, calcium restoration caused calcium influx that depended
on voltage, and decayed between 1 and 2 min after depolarization. Unlike ram,
mouse or bovine sperm, in which an alkalinization is required to induce calcium
influx with potassium, the voltage-dependent calcium influx observed in human
sperm did not require an increase in internal or external pH. However, we
observed that ammonium, which increases intracellular pH, enhanced the voltage
dependent calcium influx about 90%. Furthermore, depolarization by itself caused
a small increase in intracellular pH suggesting that pH can be regulated by
membrane potential in human sperm.
PMID- 9651468
TI - The R8-photoreceptor equivalence group in Drosophila: fate choice precedes
regulated Delta transcription and is independent of Notch gene dose.
AB - It has been suggested that lateral specification of cell fate by Notch signaling
depends on feedback on Notch (N) and Delta (Dl) transcription to establish
reciprocal distributions of the receptor and its ligand at the protein level. In
Drosophila neurogenesis the predicted reciprocal protein distributions have not
been observed. Either this model of lateral specification or the description of N
and/or Dl protein distributions must be incomplete. We have reexamined R8
photoreceptor specification in the developing eye to resolve this question for
this example of lateral specification. N and Dl protein levels were assessed in
the cell as a whole and at the cell surface, where these proteins were mostly
found at the intercellular cell junctions. Protein levels did not correspond to
Notch signaling in wild type. However, Dl transcription and protein levels did
correlate with altered N signaling in mutant genotypes. Our findings suggest the
difference relates to the speed of lateral specification in vivo. The time
required for N signaling to inhibit ato expression was at most 90 min, but
changes in the Dl protein distribution in mutant genotypes arose more slowly. N
expression was little regulated by N signaling, but protein encoded by the Nts1
allele was temperature-sensitive for appearance at the cell surface. Some aspects
of the pattern of Dl protein appeared to be due to endocytosis. We conclude that
feedback of N signaling on Dl transcription does occur but is too slow to account
for the pattern of R8 specification. Studies of ommatidia mosaic for a Notch
duplication, or for the Nts1 allele at semi-restrictive temperatures, found that
cells beginning with less N activity were not necessarily predisposed to be
selected for R8 differentiation. Our data argue that other signals may be
responsible for the pattern of R8 cell fate allocation by N. Potential relevance
to other neurogenic regions is discussed.
PMID- 9651469
TI - Triggerable liposomal fusion by enzyme cleavage of a novel peptide-lipid
conjugate.
AB - A novel peptide-lipid sensitive to enzyme cleavage was designed to generate
liposomes that could be triggered to fuse by enzymatic activation. Covalent
linkage of dioleoyl phosphatidylethanolamine (DOPE) to an elastase substrate, N
acetyl-ala-ala-, resulted in a cleavable peptide-lipid (N-Ac-AA-DOPE) with no
intrinsic fusogenic activity. Cleavage of N-Ac-AA-DOPE and concomitant conversion
to the fusogenic lipid DOPE could be detected after treatment with human
leukocyte elastase or proteinase K, two proteases with similar substrate
specificities. A strategy to utilize this cleavage to trigger fusogenicity was
tested by modeling the fusion of liposomes containing the expected product of
complete cleavage. Based on these results liposomes were designed to contain N-Ac
AA-DOPE, DOTAP, and PE in the ratio of 15/15/70. These liposomes exhibited lipid
mixing with acceptor liposomes after elastase or proteinase K protease treatment.
Activation of fusion, as monitored by a lipid mixing assay, appeared to be
dependent on protease activity, as (1) heat inactivated enzyme did not activate
liposomal fusion, and (2) the time and concentration dependence of proteinase K
mediated cleavage of N-Ac-AA-DOPE correlated with membrane mixing. Liposomes
could also be formulated that exhibited lipid mixing and transfer of aqueous
fluorescent probe with erythrocyte ghosts. These observations demonstrate
fusogenic lipids conjugated to enzyme substrates serve as triggerable fusion
systems that may be useful for gene and drug delivery.
PMID- 9651470
TI - Partial respecification of nasotemporal polarity in double-temporal chick and
chimeric chick-quail eyes.
AB - In chick embryos, naso-temporal polarity of the retina becomes established before
Hamburger-Hamilton stage 10. To examine the plasticity of the early eye anlage,
double-temporal eyes were made using stage 10-11 (E1.5) chick embryos and stage 8
9 quail embryos. In vivo and in vitro experiments revealed that these double
temporal compound eyes were not completely temporal but nasal in a large
peripheral part of the graft. Four hours after transplantation, the nasal
specific fork head transcription factor CBF1 was not expressed in double-temporal
eyes but was clearly detectable 24 h later. This suggests that in the peripheral
part of the graft, temporal positional values were changed into nasal positional
values by a respecification process.
PMID- 9651471
TI - A proton-translocating H+-ATPase is involved in C6 glial pH regulation.
AB - Glial cells extrude acid equivalents to maintain pHi. Although four mechanisms
have been described so far, pHi-control under physiological conditions is still
not sufficiently explained. We therefore investigated whether a H+-translocating
ATPase is involved in glial pHi homeostasis using an established glial cell line
(C6 glioma). In the absence of bicarbonate, the inhibition of H+-ATPases by NEM
led to a pHi decrease. The application of a more specific inhibitor (NBD-Cl)
showed that the H+-ATPase involved is of the vacuolar type. Inhibition went along
with delayed cell swelling. Together with the fact that glial acidification was
far more pronounced in Na+-free media, this may serve as evidence for a secondary
activation of Na+/H+-exchange once an activation setpoint is reached, which in
turn causes secondary swelling from Na+-uptake. Stimulation of Na+/H+-exchange by
PMA can increase the setpoint. pHi-recovery after an acid load was blocked by the
inhibition of v-type H+-ATPase, if pHi did not reach 6.6 during the acid load.
The inhibition of Na+/H+-exchange by amiloride inhibited recovery only if
acidification was below the threshold. Finally, in bicarbonate-free media a v
type H+-ATPase contributes to pH-regulation in glial cells, especially during pH
homeostasis at physiological conditions, while Na+/H+-exchange gains significance
during severe acid loads.
PMID- 9651472
TI - Structural and functional analysis of the BMP-4 promoter in early embryos of
Xenopus laevis.
AB - The Xenopus laevis BMP-4 gene shows an evolutionary conserved structure
containing two coding exons and a leader exon. The transcripts which are detected
after zygotic activation of the gene in ventral mesoderm of late blastula stage
embryos do either contain the leader exon or begin within the first intron.
Luciferase reporter/promoter studies revealed multiple elements being required
for the activation and for the spatial control of transcription. These elements
are located within the upstream region and within the second intron and they
interact with a most proximal located basal promoter being indispensable for
transcriptional activation. The auto-activatory capacity of BMP-4 is mediated by
several enhancer elements being responsive not only to BMP-4 but also to BMP-2
signaling. BMP-2 might thus function as a natural activator of the BMP-4 gene in
the early embryo. Since reporter activity obtained with distinct BMP-2/4
responsive promoter deletion mutants is simultaneously inhibited by the dominant
negative BMP receptor as well as by chordin, we suggest that down-regulation of
the BMP-4 gene by chordin results from an interference with the auto-regulatory
loop at the level of protein-protein interactions.
PMID- 9651473
TI - Multiple Sp1 sites efficiently drive transcription of the TATA-less promoter of
the human glypican 3 (GPC3) gene.
AB - Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked disease characterized by pre
and postnatal overgrowth. Recently, we have shown that mutations in the glypican
family gene, GPC3, cause SGBS. This gene is predominantly expressed in the same
mesoderm-derived tissues that overgrow in its absence. To investigate the basis
for promoter function, 3.3kb of GC-rich DNA 5' of the transcribed region were
fused to a luciferase cDNA, transfected into Caco-2 and NT2 cells, and assayed
for activity. Deletion analysis identified a 218-bp fragment upstream of the
transcription start site that conferred more than 80% of maximal reporter gene
activation. This fragment contains five putative Sp1 binding sites, three of
which (centered at nt -14, -34, and -92) were active when assessed by DNaseI
footprinting and gel shift/supershift assays. Additionally, Sp1 specifically
transactivated transcription in Sp1-deficient Drosophila SL2 cells, demonstrating
the functionality of Sp1 on the GPC3 promoter. A full-length promoter construct
was also highly active in HeLa cells, which do not express endogenous GPC3. These
results indicate that the GPC3 promoter is dependent on Sp1 for proper
activation, but tissue-specific repression in non-expressing cells must involve
either DNA that lies outside the region tested or auxiliary structural features
of chromatin.
PMID- 9651474
TI - Modulatory drug action in an allosteric Markov model of ion channel behaviour:
biphasic effects with access-limited binding to either a stimulatory or an
inhibitory site.
AB - Concentration-dependent biphasic effects of drugs on ion channel activity have
been reported in a variety of preparations, usually with stimulatory effects seen
at low concentrations followed by increasingly dominant inhibition at higher
levels. Such behaviour is often interpreted as evidence for the existence of
separate modulatory drug binding sites. We demonstrate in this paper that it is
possible for biphasic effects to be produced in an allosteric model of a ligand
activated ion channel, where diffusion-limited binding of the modulatory drug is
restricted to either a stimulatory or an inhibitory site (but not both) because
of steric overlap. The possibility of such an interaction mechanism should be
kept in mind when interpreting experimental data if stoichiometric evidence from
complementary techniques suggests that only one drug molecule is bound per
receptor/ion channel complex.
PMID- 9651475
TI - The loss of ventral ectoderm identity correlates with the inability to form an
AER in the legless hindlimb bud.
AB - We have characterized the early stages of murine hindlimb morphogenesis in the
legless (lgl)mutant and non-mutant littermates. Initially the entire ventral
ectoderm expresses many genetic markers characteristic of the AER (en-1, fgf-8,
msx-2, dlx-2, cd44, and cx-43). Subsequently, the expression domain of most of
these genes is restricted to the thickened ectoderm of the disto-ventral limb
margin prior to forming an AER. In lgl, the expression of these genes is
initiated but not maintained and the disto-ventral marginal ectoderm does not
thicken. In contrast, Wnt7a expression is initiated and maintained in the dorsal
ectoderm. The limb mesenchyme of lgl and non-mutant embryos initially expresses
lmx-1b and fgf-10 uniformly. As the ventro-distal marginal ectoderm thickens, lmx
1b is progressively dorsally restricted in non-mutants but continues to be
expressed ventrally in lgl hindlimb buds. These data suggest that establishment
of a dorso-ventral ectodermal interface is not sufficient for AER formation and
that restriction of lmx-1b to the dorsal mesenchyme is coordinately linked to AER
formation.
PMID- 9651476
TI - Polymorphism in the 5' flanking region of the human somatostatin receptor subtype
5.
AB - The human somatostatin receptor subtype 5 (hSSTR5) gene has previously been
cloned and localized to chromosome 16 p13.3. This region is evolutionarily
conserved in all vertebrate genomes from the puffer fish (Fugu rubripes) to
human, and also contains loci for genes associated with two common multisystemic
disorders, adult polycystic kidney disease (PKD1) and tuberous sclerosis (TSC2).
Analysis of the 5' flanking region of the hSSTR5 gene has revealed consensus
sequences for a number of transcription factors as well as Alu-like repeat
elements. In the present study, genomic DNA from 53 unrelated individuals was
analysed by PCR and Southern blots probed with radiolabeled fragments generated
from different segments of the hSSTR5 gene. We have identified two restriction
fragment length polymorphisms (RFLP) with high heterozygosity values at the 5'
flanking region of the hSSTR5 gene. These RFLP markers will be useful for
determining the allelic loss of genetic material from this region. The observed
polymorphism in the promoter region may affect the function of the hSSTR5 gene.
PMID- 9651477
TI - Lipid interactions with human antiphospholipid antibody, beta 2-glycoprotein 1,
and normal human IgG using the fluorescent probes NBD-PE and DPH.
AB - Recurrent venous thrombosis, arterial thrombosis and pregnancy losses are
clinical manifestation associated with antiphospholipid antibody (aPL) that
recognizes negatively charged phospholipid antigens. Enzyme-linked immunosorbent
assays (ELISA) are generally used to determine the presence and specificity of
aPL. In this paper, a fluorescence spectroscopy method has been applied, through
monitoring the alteration of fluorescence intensity and anisotropy of a
fluorophore that was incorporated in liposomes to explore the changes of
molecular structure or configuration elicited by the binding aPL with
phospholipid antigens. The bilayer surface was markedly ordered by aPL binding as
indicated by the surface-sensitive probe NBD-PE. The binding of aPL on the
bilayer surface is saturable. The saturation concentration of aPL is 40% (w/w,
aPL/lipid) for cardiolipin membranes. The binding of aPL on cardiolipin took
place in the absence of beta 2-GP1. The addition of beta 2-GP1 further increased
the anisotropy and decreased the intensity of fluorescence. The binding of aPL is
predominantly attributed to electrostatic interaction, but the configuration of
the acyl chains of phospholipid also plays a role. It is found that the thermal
history is important for aPL binding. The incubation at 37 degrees C is more
favorable for aPL binding than ambient temperature. Normal human serine (IgG-NHS)
did not elicit any distinct change of NBD-PE fluorescence, which indicates it
does not interact with the lipid.
PMID- 9651478
TI - Identification of a short interspersed repetitive element in partially spliced
transcripts of the bell pepper (Capsicum annuum) PAP gene: new evolutionary and
regulatory aspects on plant tRNA-related SINEs.
AB - In bell pepper, a gene encoding a major plastid-lipid associated protein is
expressed as both partially and totally spliced transcripts (respectively PAP2
and PAP1). Although PAP is present as a single-copy gene in the bell pepper
genome, Southern blots using PAP2 as a probe revealed multiple homologous copies.
Analyses of the intronic sequence of PAP2 showed the existence of a 206bp short
interspersed repetitive element (SINE) belonging to the Ts family of
retrotransposons (Yoshioka et al., 1993). Comparison with PAP sequences in other
Solanaceae species suggested that the structure of the gene is highly conserved:
the two introns are inserted at the same position. However, the Ts insertion
found in bell pepper is absent in tobacco and tomato. Studies using RT-PCR showed
that in these latter species only totally spliced transcripts of PAP are present.
On the other hand, RNA analyses of tobacco plants transformed with the bell
pepper PAP revealed the presence of both totally and incompletely spliced
transcripts. Altogether our results support the hypothesis that the Ts insertion
into the first intron of PAP results in a splicing defect of the corresponding
pre-mRNA. Based on the presence of peculiar, previously unidentified Ts elements,
a possible horizontal transmission of Ts elements from animals to plants is
discussed.
PMID- 9651479
TI - Linking cell-fate specification to planar polarity: determination of the R3/R4
photoreceptors is a prerequisite for the interpretation of the Frizzled mediated
polarity signal.
AB - The adult eye of Drosophila is a highly ordered structure composed of about 800
ommatidia, each displaying precise polarity. The planar polarity is reflected in
the mirror-symmetric arrangement of ommatidia relative to the dorso-ventral
midline, the equator. This arrangement is generated when ommatidia rotate towards
the equator and the photoreceptor R3 displaces R4 creating different chiral forms
in each half. Analysis of ommatidia mosaic for the tissue polarity gene frizzled
(fz) has shown that the presence of a single Fz+ photoreceptor cell within the
R3/ R4 pair is critical for the direction of rotation and chirality. By analysing
clones mutant for seven-up (svp), in which R3/R4 precursors reside in their
normal positions and become photoreceptor neurones but fail to adopt the normal
R3/R4 fate, we find that the R3/R4 photoreceptor subtype specification is a
prerequisite for planar polarisation in the eye. Moreover, in mosaic R3/R4 pairs
we find that the svp- cell always adopts the R4 position. This bias is
reminiscent of what happens in fz mosaic R3/R4 pairs, where the fz- cell also
almost always adopts the R4 position. In addition, we find that in genotypes
where too many cells adopt the R3/R4 fate, ommatidial polarity is also disturbed.
Taken together, these data imply that correct specification of a single R3 cell
per ommatidium is essential for the normal interpretation of the Fz-mediated
polarity signal.
PMID- 9651480
TI - Delivery of an anti-HIV-1 ribozyme into HIV-infected cells via cationic
liposomes.
AB - Cationic liposome-mediated intracellular delivery of a fluorescein-labeled
chimeric DNA-RNA ribozyme targeted to the HIV-1 5' LTR was investigated, using
THP-1, THP-1/HIV-1IIIB or HeLa/LAV cells. Different fluorescence patterns were
observed when the cells were exposed to Lipofectamine, Lipofectin or DMRIE:DOPE
(1:1) complexed to the ribozyme. With Lipofectamine intense cell-associated
fluorescence was found. Incubation with Lipofectin resulted in less intense
diffuse fluorescence, while with DMRIE an intense but sporadic fluorescence was
observed. Differentiated THP-1/HIV-1IIIB cells were more susceptible to killing
by liposome-ribozyme complexes than THP-1 cells. Under non-cytotoxic conditions
(a 4-h treatment) complexes of 5, 10 or 15 microM Lipofectin or DOTAP:DOPE (1:1)
and ribozyme, at lipid:ribozyme ratios of 8:1 or 4:1, did not affect p24
production in THP-1/HIV-1IIIB cells in spite of the intracellular accumulation of
the ribozyme. A 24-h exposure of THP-1/HIV-1IIIB cells to 5 microM Lipofectin or
DOTAP:DOPE (1:1) complexed with either the functional or a modified control
ribozyme reduced virus production by approximately 30%. Thus, the antiviral
effect of the liposome-complexed ribozyme was not sequence-specific. In contrast,
the free ribozyme at a relatively high concentration inhibited virus production
by 30%, while the control ribozyme was ineffective, indicating a sequence
specific effect. Both Lipofectin and DOTAP complexed with ribozyme were toxic at
10 and 15 microM after a 24-h treatment. A 4-h treatment of HeLa/LAV cells with
Lipofectin at 5, 10 or 15 microM was not toxic to the cells, but also did not
inhibit p24 production. In contrast, treatment of HeLa CD4+ cells immediately
after infection with HIV-1IIIB at the same lipid concentrations and
lipid:ribozyme ratios was cytotoxic. Our results indicate that the delivery of
functional ribozyme into cells by cationic liposomes is an inefficient process
and needs extensive improvement before it can be used in ex vivo and in vivo
applications.
PMID- 9651481
TI - The origin and fate of pioneer myotomal cells in the avian embryo.
AB - The ontogeny of the myotome was investigated using [3H]thymidine or Brdu
treatment in conjunction with 1,1', di-octadecyl-3, 3, 3', 3',-tetramethylindo
carbocyanine perchlorate (DiI) labeling and expression of specific markers. We
have identified a subset of early post-mitotic cells that is present in the
dorsomedial aspect of epithelial somites and is homogeneously distributed along
their entire rostrocaudal extent. The post-mitotic quality of this cell subset
enabled us to trace their fate in time-course experiments. Following initial
somite dissociation, this epithelial post-mitotic layer bends underneath the
medial portion of the nascent dermomyotome. Then, these cells progressively lose
epithelial arrangement and migrate in a rostral direction where they accumulate
temporarily. Subsequently, these early post-mitotic precursors extend processes
that reach both rostral and caudal edges of each segment. Medial somite-derived
myofibers also fill the entire mediolateral extent of the segment and reach the
dorsomedial lip of the dermomyotome, thus forming the primary myotome. During
this process, their large nuclei localize to a narrow stripe in the middle of the
nascent myotome. Consistent with the proliferation studies, DiI labeling of the
medial epithelial somite cells gave rise to a primary myotomal structure, and
continuous pulsing of the DiI-injected embryos with radioactive thymidine
revealed that these fibers indeed developed from post-mitotic progenitors. As
these early post-mitotic cells that arise prior to somite dissociation are the
first wave of progenitors that constitutes the myotome, we have termed them avian
muscle pioneers. We propose that the primary myotome formed by the muscle
pioneers constitutes a longitudinal scaffold that serves as a substrate for the
addition of subsequent waves of myotomal cells.
PMID- 9651482
TI - The four cdc25 genes from the nematode Caenorhabditis elegans.
AB - During eukaryotic evolution, multicellular organisms have evolved multiple
members of gene families that may display unique, partially overlapping, or
redundant functions during development. More than 75% of the C. elegans genome
has been sequenced, which represents approximately 95% of the coding sequences.
This provides a unique opportunity to identify most, if not all, of the members
of a given gene family. We have searched the C. elegans genome database for
members of a key family of cell cycle regulators, the CDC25 phosphatases, and
have identified four genes. The four C. elegans genes represent a larger family
within a single organism than has been reported so far in Drosophila, mice and
humans. An amino acid comparison revealed a high degree of similarity and
identity within the phosphatase domain. This analysis also identified an expanded
consensus sequence that can be used to discover new members of the CDC25
phosphatase family. However, the four C. elegans sequences display a few novel
amino acid substitutions in the residues surrounding the invariant catalytic
motif CX5R. These data demonstrate the value of genome database searching for
identifying new members of known gene families, understanding genetic diversity,
and for studying gene structure.
PMID- 9651483
TI - Cloning and structure of a rabbit protein inhibitor of neuronal nitric oxide
synthase (PIN) gene and its pseudogene.
AB - Neuronal nitric oxide synthase (nNOS), the biosynthetic enzyme for the free
radical neurotransmitter nitric oxide, was found to be inhibited by the protein
inhibitor of nNOS, designated PIN (Jaffrey, S.R. and Snyder, S.H., (1996) Science
274, 774-777). The cDNA clone encoding a rabbit PIN was isolated, and the
translated PIN protein was89 amino acid long sharing 100% of its deduced amino
acid sequence with rat PIN. Using a radiolabelled riboprobe derived from the
rabbit PIN cDNA, the rabbit PIN gene was isolated from a rabbit genomic library
and the structural organization of the gene was determined. The gene contains
three exons separated by two introns spanning approx. 2.3kb of genomic DNA. 5'
RACE analysis mapped the transcriptional initiation site 98bp upstream of the
initiator methionine codon. Characterization of the 5' flanking genomic region
revealed that the rabbit PIN promoter is TATA-less, but contains a CCAAT box as
well as various putative transcription factor-binding elements. The 3'
untranslated region contains consensus polyadenylation signal (AATAAA). We also
isolated an intronless gene with 93% nucleotide sequence similarity to the rabbit
PIN cDNA. Sequence analysis indicates that the open reading frame was interrupted
by a premature stop codon and frameshift which resulted in a processed pseudogene
of the rabbit PIN.
PMID- 9651484
TI - Organization of the canine gene encoding the E isoform of retinal guanylate
cyclase (cGC-E) and exclusion of its involvement in the inherited retinal
dystrophy of the Swedish Briard and Briard-beagle dogs.
AB - Intracellular cyclic GMP concentration is known to change in response to a wide
variety of agents, including hormones, neurotransmitters or light. In vertebrate
photoreceptors, different membrane-bound guanylate cyclase isoforms are
responsible for cGMP synthesis and thus directly involved in termination of light
signalling via the phototransduction cascade and recovery of the dark state. We
have characterized a 4.7 kb long cDNA for the canine retinal guanylate cyclase
isoform E (cGC-E) predicting a polypeptide of 1109 amino acids. The genomic
structure and the complete sequence of the canine GC-E gene, which consists of 20
exons and spans about 14.5 kb, has also been determined. Northern blot analysis
showed that GC-E was expressed in the canine retina as a 4.7 and 6.1 kb large
transcript. RT-PCR analysis also detected low expression in cerebrum (occipital
lobe). We performed a sequence analysis of the cGC-E gene in animals of a Swedish
Briard and Briard-Beagle dog kinship in which an inherited retinal dystrophy is
segregating. Several intragenic DNA polymorphisms were identified and used for
segregation analysis which excluded cGC-E as a candidate gene for this type of
canine retinal dystrophy.
PMID- 9651485
TI - Ventral mesoderm induction and patterning by bone morphogenetic protein
heterodimers in Xenopus embryos.
AB - Bone morphogenetic proteins (BMPs) perform diverse functions in vertebrate
development. Here we demonstrate that the heterodimeric BMP-4/7 protein directly
induces ventral mesoderm and blood in Xenopus animal caps, and BMP-2/7
heterodimers may function similarly. We also provide indirect evidence that BMP
heterodimers function in embryos, using assays with dominant-negative BMP
ligands. Homodimeric BMP-2 and BMP-4 proteins do not induce mesoderm, but they
ventralize mesoderm induction by activin. In contrast, BMP-7 protein interferes
with mesoderm induction by activin, but BMP-7 stimulates ventral mesoderm
induction by the heterodimer, BMP-4/7. This novel property of BMP-7 distinguishes
it from other BMPs. BMP-7 may therefore function in early embryogenesis to
antagonize activin signals and potentiate BMP signals. We propose that BMP
heterodimers convey signals for ventral mesoderm induction and patterning in
Xenopus development.
PMID- 9651486
TI - Identification and functional analysis of the mouse lens filensin gene promoter.
AB - Filensin (also called CP94; CP95; CP97; 115kDa protein) is a component of the
lens-specific beaded filament which is believed to be functionally important in
lens fiber cell differentiation and in maintaining lens fiber cell conformation
and transparency. A 17.2kb fragment containing the 5'-upstream sequence of the
filensin gene was isolated. S1-mapping analysis determined the transcription
start point (tsp; +1) which locates at 94base pairs upstream from the initiating
ATG on the filensin gene. In addition to a major tsp, a minor tsp (-136) was
observed. DNA sequence of the fragment around the tsp (-2144 to +155) was
identified. Analysis of the DNA sequence of the promoter region around tsp
revealed two motifs with sequence homology to Sox2 and Maf recognition sequences
in addition to one GATA-1 site, two Sp1 binding sites, and three AP-2 binding
motifs. No TATA-box or CCAAT-motif was found around the tsp region. A series of
sequentially deleted fragments of (-2144 to +40) were fused to firefly luciferase
reporter plasmid pGL2 and tested for activity in chicken embryonic lens explants.
A minimal promoter region for mouse filensin of (-70 to +40) was identified. The
lens-specific promoter activity was detected using lens explants cultured within
12h after dissection. The activity was remarkably enhanced by culture in the
presence of 5ng/ml of basic fibroblast growth factor. Each one of the Sp1 and AP
2 binding motifs was localized to the fragment of (-27 to +40) using
electrophoretic mobility shift assays. These are the first data to identify the
basic elements to the 5'-upstream sequences of the filensin gene, namely the tsp
and the minimal filensin promoter.
PMID- 9651487
TI - Membrane permeabilisation and antimycoplasmic activity of the 18-residue
peptaibols, trichorzins PA.
AB - The membrane permeabilisation properties of six linear natural 18-residue
peptaibols, termed trichorzins PA, have been assessed on liposomes and on
mollicutes (trivial name, mycoplasmas), a class of parasitic bacteria
characterized by a small genome, the lack of a cell wall, a minute cell size, and
the incorporation in their plasma membrane of exogenously supplied cholesterol.
The trichorzins PA used in this study (PA II, PA IV-VI, PA VIII, and PA IX)
differ between them by amino acid or amino alcohol substitutions at positions 4,
7, and 18, and form slightly amphipathic alpha-helices. They proved bactericidal
for mollicutes belonging to the genera Acholeplasma, Mycoplasma, and Spiroplasma,
with minimal inhibitory concentrations (3.12=MICs=50 microM) generally 2 to 4
fold higher than those of alamethicin F50, a related 20-residue peptide
(1.56=MICs=12.5 microM). Spiroplasma cells were apparently not protected by
the presence of spiralin on their surface. The activities of the six trichorzins
PA were not influenced by their sequence variations and no synergistic effect was
observed. Consistent with the marginal effect of cholesterol on the incorporation
of the trichorzins PA into liposome bilayers, the antibiotic activity was
independent of the amount of cholesterol in the membranes of the different
mollicutes. The trichorzins PA and alamethicin inhibited the motility of
Spiroplasma melliferum, the helical cells being deformed and split into coccoid
forms. Membrane potential measurements in Acholeplasma laidlawii and S.
melliferum showed that trichorzin PA V and alamethicin F50 very efficiently
depolarized the plasma membrane of mollicutes. This was consistent with
fluorescence and 23Na NMR measurements on liposomes that revealed the
permeabilisation of the lipid bilayer and the nonselective ionophoric activity of
the trichorzins PA. These data suggest that the bactericidal activity exhibited
by the trichorzins PA on mollicutes is due to the permeabilisation of the plasma
membrane.
PMID- 9651488
TI - Emotion in the perspective of an integrated nervous system.
PMID- 9651489
TI - Structural divisions and functional fields in the human cerebral cortex.
AB - The question of what is a cortical area needs a thorough definition of borders
both in the microstructural and the functional domains. Microstructural
parcellation of the human cerebral cortex should be made on multiple criteria
based on quantitative measurements of microstructural variables, such as neuron
densities, neurotransmitter receptor densities, enzyme densities, etc. Because of
the inter-individual variations of extent and topography of microstructurally
defined areas, the final microstructurally defined areas appear as population
maps. In the functional domain, columns, patches and blobs signifying
synaptically active parts of the cortex appear as cortical functional fields.
These fields are the largest functional entities of the cerebral cortex according
to the cortical field hypothesis. In its strong version, the cortical field
hypothesis postulates that all neurons and synapses within the fields perform a
co-operative computation. A number of such fields together provide the functional
contribution of the cerebral cortex. The functional parcellation of the human
cerebral cortex must be based on field population maps, which after intersection
analysis appear as functional domains. The major structural-functional hypothesis
to be examined is whether these functional domains are equi-territorial to the
microstructurally defined meta-maps. The cortical hypothesis predicts that, if
two brain tasks make use of one or several identical or largely overlapping
fields, they cannot be performed simultaneously without errors or increases in
latency. Evidence for such interference is presented. This evidence represents a
restriction in the parallel processing of the human brain. In the posterior part
of the brain not only visual cortical areas may qualify for parallel processing,
but also the somatosensory cortices appear to have separate functional streams
for the detection of microgeometry and macrogeometry.
PMID- 9651490
TI - Comparison of sequence and function of the Oct-6 genes in zebrafish, chicken and
mouse.
AB - To examine the role of the Oct-6 gene in Schwann cell differentiation we have
cloned and characterized the chicken and zebrafish homologues of the mouse Oct-6
gene. While highly homologous in the Pit1-Oct1/2-Unc86 (POU) domain, sequence
similarities are limited outside this domain. Both genes are intronless and both
proteins lack the amino acid repeats that are a characteristic feature of the
mammalian Oct-6 proteins. However as in mammals, the aminoterminal parts of the
chicken and zebrafish Oct-6 proteins are essential for transactivation of octamer
containing promoters. By immunohistochemistry we have found that the chicken Oct
6 protein is expressed in late embryonic ensheathing Schwann cells of the sciatic
nerve and is rapidly downregulated when myelination proceeds. This expression
profile in glial cells is identical to that in the mouse and rat. Furthermore the
zebrafish Oct-6 homolog is expressed in the posterior lateral nerve at a time
when it contains actively myelinating Schwann cells. Thus despite extensive
primary sequence divergence among the vertebrate Oct-6 proteins, the expression
of the chicken and zebrafish Oct-6 proteins is consistent with the notion that
Oct-6 functions as a 'competence factor' in promyelin cells to execute the
myelination program.
PMID- 9651491
TI - Evidence for a role of the multidrug resistance protein (MRP) in the outward
translocation of NBD-phospholipids in the erythrocyte membrane.
AB - Phosphatidylserine (PS) containing a 7-nitrobenz-2-oxa-1, 3-diazol-4-yl- (NBD-)
hexanoyl residue, like native PS, preferentially distributes into the inner
membrane leaflet of human erythrocytes. In the case of NBD-PS, this preference
results from two opposite active processes, an inward translocation mediated by
the aminophospholipid flippase and an outward translocation mediated by an ill
defined floppase. Selective inhibition of this floppase by alkylating reagents or
cationic and anionic drugs increases the extent of accumulation of NBD-PS in the
inner membrane leaflet from about 70% in control cells to about 90%. Different
inhibitor sensitivities of the flippase and the floppase strongly suggest that
both represent different entities. The floppase was characterized in further
detail by comparing inhibitory effects of various compounds on this translocase
with their effects on known primary active transport systems for amphiphilic
compounds. The inhibitory effects of various drugs, glutathione conjugates and
GSSG on the floppase activity closely correlate with those reported for the
active transport by the multidrug resistance protein (MRP) while only poorly
going parallel with those for the active transport by the low affinity pump for
glutathione conjugates and the multidrug resistance MDR1 P-glycoprotein. The NBD
phospholipid floppase activity of the erythrocyte is thus probably a function of
MRP.
PMID- 9651492
TI - Characterization and targeted disruption of a glycosyltransferase gene in the
tylosin producer, Streptomyces fradiae.
AB - An open reading frame, designated tylN, has been identified by sequence analysis
at one end of the tylosin biosynthetic gene cluster of Streptomyces fradiae,
alongside a cluster of genes encoding the biosynthesis of dTDP-deoxyallose. This
6-deoxyhexose sugar is converted to mycinose, via bis O-methylation, following
attachment to the polyketide lactone during tylosin biosynthesis. The deduced
product of tylN is similar to several glycosyltransferases, authentic and
putative, and displays a consensus sequence motif that appears to be
characteristic of a sub-group of such enzymes. Specific disruption of tylN within
the S. fradiae genome resulted in the production of demycinosyl-tylosin, whereas
other glycosyltransferase activities involved in tylosin biosynthesis were not
affected. Evidently, tylN encodes deoxyallosyl transferase.
PMID- 9651493
TI - Homeotic regulation of segment-specific differences in neuroblast numbers and
proliferation in the Drosophila central nervous system.
AB - The number and pattern of neuroblasts that initially segregate from the
neuroectoderm in the early Drosophila embryo is identical in thoracic and
abdominal segments. However, during late embryogenesis differences in the numbers
of neuroblasts and in the extent of neuroblast proliferation arise between these
regions. We show that the homeotic genes Ultrabithorax and abdominal-A regulate
these late differences, and that misexpression of either gene in thoracic
neuroblasts after segregation is sufficient to induce abdominal behaviour.
However, in wild type embryos we only detect abdominal-A and Ultrabithorax
proteins in early neuroblasts. Furthermore, transplantation experiments reveal
that segment-specific behaviour is determined prior to neuroblast segregation.
Thus, the segment-specific differences in neuroblast behaviour seem to be
determined in the early embryo, mediated through the expression of homeotic genes
in early neuroblasts, and executed in later programmes controlling neuroblast
numbers and proliferation.
PMID- 9651494
TI - Mosaic structure of the cox2 gene in the petite negative yeast
Schizosaccharomyces pombe: a group II intron is inserted at the same location as
the otherwise unrelated group II introns in the mitochondria of higher plants.
AB - In contrast to homologous genes in other fungal mitochondrial genomes, the gene
encoding subunit 2 of cytochrome oxidase (cox2) in several Schizosaccharomyces
pombe strains contains a large group II intron. Its 2436 nucleotides can be
folded into a typical group II intron secondary structure, possessing all the
expected sequence motifs for subgroup IIA1 (Michel et al., 1989). This intron is
remarkable for the following reasons: (i) Five nucleotide changes were observed
compared with the continuous form of the cox2 gene in the reference strain 50 at
the 3'-exon sequence, but not in the 5'-exon. (ii) One of these changes occurred
at the splice point leading to a serine instead of a threonine residue in the
deduced cox2 polypeptide. In all cases, the alterations resulted in the
replacement of more frequently used codons by rare ones. (iii) Although the
intron is able to undergo splicing, the sequence motifs thought to be necessary
for interaction between the 5'-exon and the intron during the splicing process
(the EBS1/IBS1 as well as the EBS2/IBS2 pairings) are unusual. (iv) The intron is
inserted at the same location in the cox2 gene as the otherwise unrelated intron
from higher plants.
PMID- 9651495
TI - Enhanced efficiency of a targeted fusogenic peptide.
AB - Membrane targeting was investigated as a potential strategy to increase the
fusogenic activity of an isolated fusion peptide. This was achieved by coupling
the fusogenic carboxy-terminal part of the beta-amyloid peptide (Abeta, amino
acids 29-40), involved in Alzheimer's disease, to a positively charged peptide
(PIP2-binding peptide, PBP) interacting specifically with a naturally occurring
negatively charged phospholipid, phosphatidylinositol 4, 5-bisphosphate (PIP2).
Peptide-induced vesicle fusion was spectroscopically evidenced by: (i) mixing of
membrane lipids, (ii) mixing of aqueous vesicular contents, and (iii) an
irreversible increase in vesicle size, at concentrations five to six times lower
than the Abeta(29-40) peptide. In contrast, at these concentrations the PBP
Abeta(29-40) peptide did not display any significant activity on neutral
vesicles, indicating that negatively charged phospholipids included as targets in
the membranes, are required to compensate for the lower hydrophobicity of this
peptide. When the alpha-helical structure of the chimeric peptide was induced by
dissolving it in trifluoroethanol, an increase of the fusogenic potential of the
peptide was observed, supporting the hypothesis that the alpha-helical
conformation of the peptide is crucial to trigger the lipid-peptide interaction.
The specificity of the interaction between PIP2 and the PBP moiety, was shown by
the less efficient targeting of the chimeric peptide to membranes charged with
phosphatidylserine. These data thus demonstrate that the specific properties of
both the Abeta(29-40) and the PBP peptide are conserved in the chimeric peptide,
and that a synergetic effect is reached through chemical linkage of these two
fragments.
PMID- 9651496
TI - Functional magnetic resonance imaging of mental rotation and memory scanning: a
multidimensional scaling analysis of brain activation patterns.
PMID- 9651497
TI - An internet-accessible database of mouse developmental anatomy based on a
systematic nomenclature.
AB - This paper reports an internet-accessible database of mouse developmental anatomy
(DMDA) that currently holds a hierarchy of the names and synonyms of the tissues
in the first 22 Theiler stages of development (E1-E13.5), together with other
appropriate information. The purposes of the database are to provide, first, a
nomenclature for analyzing normal and mutant mouse anatomy, and second a language
for inputting, storing and querying gene-expression and other spatially organized
data. DMDA currently contains some 6900 named and staged tissues (e.g. 360 and
1161 tissues in Theiler stage (TS) 14 (E9) and TS22 (E13.5) embryos). DMDA will
be extended to include further lineage and other data when it becomes available.
The database can be interactively accessed over the internet using either a Java
or a non-Java WWW browser at http://genex.hgu.mrc.ac.uk/.
PMID- 9651498
TI - Salient features of synaptic organisation in the cerebral cortex.
AB - The neuronal and synaptic organisation of the cerebral cortex appears exceedingly
complex, and the definition of a basic cortical circuit in terms of defined
classes of cells and connections is necessary to facilitate progress of its
analysis. During the last two decades quantitative studies of the synaptic
connectivity of identified cortical neurones and their molecular dissection
revealed a number of general rules that apply to all areas of cortex. In this
review, first the precise location of postsynaptic GABA and glutamate receptors
is examined at cortical synapses, in order to define the site of synaptic
interactions. It is argued that, due to the exclusion of G protein-coupled
receptors from the postsynaptic density, the presence of extrasynaptic receptors
and the molecular compartmentalisation of the postsynaptic membrane, the synapse
should include membrane areas beyond the membrane specialisation. Subsequently,
the following organisational principles are examined: 1. The cerebral cortex
consists of: (i) a large population of principal neurones reciprocally connected
to the thalamus and to each other via axon collaterals releasing excitatory amino
acids, and, (ii) a smaller population of mainly local circuit GABAergic neurones.
2. Differential reciprocal connections are also formed amongst GABAergic
neurones. 3. All extrinsic and intracortical glutamatergic pathways terminate on
both the principal and the GABAergic neurones, differentially weighted according
to the pathway. 4. Synapses of multiple sets of glutamatergic and GABAergic
afferents subdivide the surface of cortical neurones and are often co-aligned on
the dendritic domain. 5. A unique feature of the cortex is the GABAergic axo
axonic cell, influencing principal cells through GABAA receptors at synapses
located exclusively on the axon initial segment. The analysis of these salient
features of connectivity has revealed a remarkably selective array of
connections, yet a highly adaptable design of the basic circuit emerges when
comparisons are made between cortical areas or layers. The basic circuit is most
obvious in the hippocampus where a relatively homogeneous set of spatially
aligned principal cells allows an easy visualization of the organisational rules.
Those principles which have been examined in the isocortex proved to be identical
or very similar. In the isocortex, the basic circuit, scaled to specific
requirements, is repeated in each layer. As multiple sets of output neurones
evolved, requiring subtly different needs for their inputs, the basic circuit may
be superimposed several times in the same layer. Tangential intralaminar
connections in both the hippocampus and isocortex also connect output neurones
with similar properties, as best seen in the patchy connections in the isocortex.
The additional radial superposition of several laminae of distinct sets of output
neurones, each representing and supported by its basic circuit, requires a co
ordination of their activity that is mediated by highly selective interlaminar
connections, involving both the GABAergic and the excitatory amino acid releasing
neurones. The remarkable specificity in the geometry of cells and the selectivity
in placement of neurotransmitter receptors and synapses on their surface,
strongly suggest a predominant role for time in the coding of information, but
this does not exclude an important role also for the rate of action potential
discharge in cortical representation of information.
PMID- 9651499
TI - Differential activation of system A and betaine/GABA transport in MDCK cell
membranes by hypertonic stress.
AB - Accumulation of osmolytes by renal cells is due in part to increased uptake via
specific transporters. These include amino acid transport system A and the
betaine/GABA transporter (BGT1). Transport changes have been characterized using
intact cells which makes the intracellular mechanisms difficult to determine. In
this study the hypertonic upregulation of system A and BGT1 was studied directly
at the membrane level in Madin-Darby canine kidney (MDCK) cells. Both system A
and BGT1 transport systems were detected in an isolated membrane fraction
containing plasma membranes. System A transport was increased in membranes
prepared from cells after 6 h hypertonic stress (449 mosmol/kg) but BGT1 activity
was minimal and not different from isotonic controls. The increase in system A
was blocked by inhibitors of RNA and protein synthesis. BGT1 transport was
induced in membranes prepared after 24 h hypertonicity. At this time system A
activity in the membrane fraction remained increased, unlike the downregulation
observed in intact MDCK cells. We conclude that differential upregulation of
system A and BGT1 by hypertonic stress is due to intrinsic changes in these
transporters at the membrane level. In contrast, the downregulation of system A
in intact cells when hypertonicity is prolonged for 24 h is likely due to the
action of an intracellular repressor that is not present in the isolated
membranes.
PMID- 9651500
TI - Three alternatively spliced mouse slow skeletal muscle troponin T isoforms:
conserved primary structure and regulated expression during postnatal
development.
AB - We have cloned and sequenced full-length cDNAs encoding mouse slow skeletal
muscle troponin T (sTnT). Alternative mRNA splicing-generated two high Mr
isoforms and one low Mr sTnT isoform differing in the NH2-terminal primary
structure have been identified by Western blotting, reverse transcription
polymerase chain reaction and cDNA cloning/expression analyses. Together with a
5'-alternative exon that was also found in human sTnT encoding an 11-amino-acid
acidic segment, the results revealed a novel alternative splicing pathway to
include or exclude a three-base segment to generate additional sTnT isoforms with
NH2-terminal charge variations. Overriding the phylogenetic divergence, primary
structure of sTnT is better conserved between mammalian and avian species than
that of cardiac, fast and skeletal muscle TnTs from one species. Western blots
demonstrate four expression patterns of sTnT during postnatal skeletal muscle
development: (1) a decrease to a non-detectable level in mouse masseter, (2) an
increase to become the sole TnT in sheep masseter, (3) an increase of the total
level as well as the proportion of the low Mr isoform in sheep diaphragm and, (4)
no significant change in total level or high/low Mr isoform ratio in sheep
gastrocnemius. The highly conserved primary structure and fiber type-specific and
developmentally regulated expression of sTnT indicate a physiological importance
of this under-studied member of the TnT gene family.
PMID- 9651501
TI - Mammalian and Drosophila dachshund genes are related to the Ski proto-oncogene
and are expressed in eye and limb.
AB - We have isolated mammalian homologues of the Drosophila dachshund gene. Two
domains of high conservation, one of which contains an alpha-helical, coiled-coil
motif, show similarity to the Ski family of genes. We therefore propose that
Dachshund belongs to a superfamily including these genes. Mouse Dachshund (Dach)
is expressed in the eye and limb, structures affected by the Drosophila loss-of
function mutant, and rib primordia, CNS and genital eminence. Pax6 and Dach show
overlapping but non-identical expression patterns. Dach expression is unaffected
in smalleye mouse brain, indicating that Pax6 is not directly activating Dach. In
Drosophila eye development dachshund is a component of an interacting network of
proteins. Genes homologous to many of these exist in mammals; Dach joins this
expanding group.
PMID- 9651502
TI - Interaction of DPPC monolayers with soluble surfactants: electrostatic effects of
membrane perturbants.
AB - We studied the effects of four soluble surfactants on DPPC monolayers to
elucidate the action of these membrane perturbants. The presence of nonionic N-9
and amphoteric C31G strongly affected the pure DPPC isotherm, while anionic SDS
and cationic DTAB had little effect. The impact of surfactant on DPPC domain
shape in the liquid condensed-liquid expanded coexistence region showed the
opposite result. Neutral surfactants had minimal effect on the shape of DPPC
domains; charged surfactants, on the other hand, induced a new shape transition
at high surface pressures previously unreported for DPPC domains. All of these
results are discussed with particular attention given to electrostatic effects at
the interface.
PMID- 9651503
TI - Identification of a novel casein kinase-1 homolog in fission yeast
Schizosaccharomyces pombe.
AB - Fission yeast cells lacking either the ste9+- or rum1+ function cannot enter the
cell differentiation pathway upon nutritional starvation. Sterility in both
mutants is suppressed by the srs1-S41 mutation. A gene encoding a novel casein
kinase-1 (CK1) isoform, cki3+, was isolated as a high-copy-number suppressor gene
of the srs1 mutation. Cki3 protein is structurally more related to the Cki/Yck
subfamily proteins than those of the Hhp/Hrr25 subfamily. A mutant cki3 gene in
which a highly conserved lysine residue in the kinase subdomain II was
substituted to arginine lost the ability to recover the growth defect in the srs1
mutant, indicating that catalytic activity was necessary for suppression. Gene
disruption revealed that cki3+ was dispensable for cell viability, and cells
lacking functional cki3+ exhibited no characteristic phenotype. Thus, S. pombe
has three highly related CK1 isoforms (Cki1, Cki2 and Cki3), but none of them has
an essential function.
PMID- 9651504
TI - The Xcad-2 gene can provide a ventral signal independent of BMP-4.
AB - Patterning of the marginal zone in the Xenopus embryo has been attributed to
interactions between dorsal genes expressed in the organizer and ventral-specific
genes. In this antagonistic interplay of activities, BMP-4, a gene that is not
expressed in the organizer, provides a strong ventralizing signal. The Xenopus
caudal type homeobox gene, Xcad-2, which is expressed around the blastopore with
a gap over the dorsal lip, was analyzed as part of the ventral signal. Xcad-2 was
shown to efficiently repress during early gastrula stages the dorsal genes gsc,
Xnot-2, Otx-2, XFKH1 and Xlim-1, while it positively regulates the ventral genes,
Xvent-1 and Xvent-2, with Xpo exhibiting a strong positive response to Xcad-2
overexpression. Xcad-2 was also capable of inducing BMP-4 expression in the
organizer region. Support for a ventralizing role for Xcad-2 was obtained from co
injection experiments with the dominant negative BMP receptor which was used to
block BMP-4 signaling. Under lack-of-BMP-signaling conditions Xcad-2 could still
regulate dorsal and ventral gene expression and restore normal development,
suggesting that it can act downstream of BMP-4 signaling or independently of it.
Xcad-2 could also inhibit secondary axis formation and dorsalization induced by
the dominant negative BMP receptor. Xcad-2 was also shown to efficiently reverse
the dorsalizing effects of LiCl. These results place Xcad-2 as part of the
ventralizing gene program which acts during early gastrula stages and can execute
its ventralizing function in the absence of BMP signaling.
PMID- 9651505
TI - In vitro reconstitution of stratum corneum lipid lamellae.
AB - In the final stages of differentiation in the epidermis of terrestrial mammals,
lipids are extruded into the intercellular spaces. The initially extruded lipid
becomes transformed into broad, multilamellar sheets that are found in the
intercellular spaces throughout the stratum corneum. These lamellae display an
unusual alternating broad-narrow-broad pattern of lucent bands as revealed by
transmission electron microscopy (TEM). This arrangement results in two
periodicities that can be measured from electron micrographs and are also evident
in X-ray diffraction-5 nm (broad) and 13 nm (broad-narrow-broad). The goal of the
present study was to reconstitute these lamellae in vitro. Porcine stratum
corneum lipids were applied to Millipore filters. The disks were placed in water
and heated to 80 degrees C for 1 h. After cooling, the disks were stored over
desiccant. At each stage, the disks were prepared for TEM. TEM revealed that the
application of the lipid solutions onto the disks resulted to deposition of
mostly amorphous material. Heating in water resulted in the formation of many
lamellae. The width of the lamellae was uniform and in the range of 5 to 6 nm
with no broad-narrow-broad pattern; however, after storage under desiccating
conditions, the broad-narrow-broad pattern was reproduced.
PMID- 9651506
TI - The emergence of the volume transmission concept.
AB - Interneuronal communication in the central nervous system (CNS) have always been
of basic importance for theories on the cerebral morphofunctional architecture.
Our group has proposed that intercellular communication in the brain can be
grouped into 2 broad classes based on some general features of the transmission:
wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained
cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in
the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both
morphological and functional evidence indicates that dopamine (DA) synapses in
striatum are 'open' synapses, i.e., synapses which favor diffusion of the
transmitter into the surrounding ECF and observations are compatible with the
view that DA varicosities can synthesize, store and release DA for VT. The
DAergic mesostriatal transmission has, therefore, been examined by several groups
to give experimental support to VT. Moreover, due to its minor structural
requirements, VT may become prevalent under some pathological conditions, e. g.
Parkinson's disease. In animal models of DAergic pathway degeneration, it has
been shown that a compensatory activation of surviving DA terminals may lead to a
preferential potentiation of VT. WT and VT favor different and complementary
types of computation. VT is markedly slower and less safe than WT, but has minor
spatial constraints and allows the reach of a large number of targets. Models of
neuronal systems integrating classical neuronal circuits and diffusible signals
begin to show how WT and VT may interact in the neural tissue.
PMID- 9651507
TI - Novel testis-specific protein that interacts with heat shock factor 2.
AB - Although heat shock factor 2 (HSF2) binds to heat shock element (HSE)
constitutively during differentiation, development and spermatogenesis, little is
known about the nature and mechanism of transcriptional control of heat shock
genes by HSF2. We screened a human testis cDNA library for proteins that can
associate with HSF2 by the yeast two-hybrid system, and isolated clones encoding
a novel protein, designated HSF2 binding protein (HSF2BP), that associates with
HSF2 in vitro and in vivo and is specifically expressed in testis. The
interaction seemed to occur between the trimerization domain of HSF2 and the
amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper
motifs. HSF2BP may therefore be involved in modulating HSF2 activation in testis.
PMID- 9651508
TI - Free liposomes enhance the transfection activity of DNA/lipid complexes in vivo
by intravenous administration.
AB - Factors that regulate the transfection efficiency of cationic lipid-based
carriers are still largely unknown. We have shown in a previous report [F. Liu,
H.W. Qi, L. Huang, D. Liu, Factors controlling the efficiency of cationic lipid
mediated transfection in vivo via intravenous administration, Gene Ther., 4
(1997) 517-523. ] that the transfection efficiency, to the lung, of a lipid
formulation composed of N-[1-(2,3-dioleoyloxy)propyl-N,N, N-trimethylammonium
chloride (DOTMA) and Tween 80 is directly proportional to the ratio of DOTMA to
DNA. In this study, we investigated the mechanism underlying the high cationic
lipid to DNA ratio dependent transfection activity. Specifically, we have
examined the role of free cationic liposomes in affecting the transfection
efficiency of the DNA/lipid complexes in vivo by intravenous administration. The
data show that greater transfection activity of DNA/lipid complexes in the lung
at a higher cationic lipid to DNA ratio is due to the function of free liposomes
present in the DNA/lipid mixture. Free liposomes enhance the transfection
activity of DNA/lipid complexes by increasing the retention time of DNA and
decreasing transgene degradation in different organs. In addition to DOTMA
liposomes, liposomes composed of 1,2-dioleoyl-3-trimethylammonium propane
chloride (DOTAP) and 3beta[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol
(DC-Chol) also enhance the level of gene expression in animals transfected by
DNA/DOTMA complexes. These results suggest that inclusion of free liposomes into
the DNA/lipid complexes may be important in achieving an optimal transfection
activity in vivo.
PMID- 9651509
TI - A role for Xenopus Frizzled 8 in dorsal development.
AB - The establishment of cell and tissue polarity during animal development often
requires signaling by Wnts, extracellular signaling polypeptides. Transmembrane
receptors of the Frizzled family are implicated in the transduction of Wnt
signals in responding cells. Xfz8 is a novel cDNA encoding a Xenopus homologue of
mouse Frizzled 8. Xfz8 transcripts are expressed zygotically in the organizer at
the early gastrula stage and in the most anterior ectoderm at later stages,
suggesting a role in axis specification. When Xfz8 mRNA is overexpressed in
ventral marginal zone cells, a secondary body axis with prominent head structures
develops. Surprisingly, axis induction was not accompanied by activation of early
dorsal marginal zone markers at the gastrula stages, whereas Xwnt8 induced these
markers with high efficiency. These findings suggest that Xfz8 is a product of
the organizer and mimics its function. Head induction by Xfz8 was blocked by co
expression of GSK3beta or a dominant negative form of Xenopus Dishevelled,
suggesting that this effect of Xfz8 requires Wnt signal transduction. When Xfz8
is overexpressed in animal pole cells, dorsal marginal zone markers Xnr3, Xotx2
and a promoter construct for Siamois, were selectively activated, demonstrating
the difference in competence between animal pole cells and ventral marginal zone
cells in response to Xfz8. It is proposed that the Wnt pathways are activated at
two different steps during axis formation: to induce the Spemann organizer and to
implement organizer functions by triggering dorsoanterior development.
PMID- 9651510
TI - Identification of two Y-box binding proteins that interact with the promoters of
columbid annexin I genes.
AB - Two annexin I (anxI) genes, called cp35 and cp37, are expressed from the pigeon
(Columba livia) genome, but they are regulated differently at both the
transcriptional and post-transcriptional levels. The proximal promoter elements
of these two genes are very similar. A conserved sequence from the cp35 and cp37
promoters bound specifically with proteins present in cropsac cell extracts. This
sequence of DNA was used to screen a lambdagt11 cDNA expression library. Clones
encoding two pigeon Y-box binding proteins (YB) were isolated. One of the pigeon
YB cDNAs was found to be most similar to YB1 from other species, and the other
was most similar to chicken YB2. Each YB is encoded by a single-copy gene in the
pigeon, and their mRNAs are expressed in many tissues. On Northern blots, the
sizes of the mRNAs encoding pigeon YB1 (pYB1) and pigeon YB2 (pYB2) were 1.8 and
1.7kb, respectively. The sequences of both pYB1 and pYB2 diverge from their
previously identified relatives in the N-terminal domain 'A'. Antisera were
developed to unique peptide epitopes in YB1 or 2. Affinity-purified anti-YB1 and
anti-YB2 detected immunoreactive proteins in extracts from a variety of pigeon
tissues, including the cropsac. To confirm that pYB1 and pYB2 interact with the
cp35 promoter, electrophoretic gel mobility shift reactions were carried out in
the presence or absence of YB antibodies. Binding to the cp35 promoter was
specifically neutralized by either anti-pYB1 or anti-pYB2. These results are the
first evidence that two YB proteins simultaneously bind to a promoter element,
and thereby may interact during regulation of gene expression.
PMID- 9651511
TI - Re-evaluation of the role of the dopamine transporter in dopamine system
homeostasis.
AB - Mice with a genetic deletion of the dopamine transporter (DAT) were used to
assess its role in the function of dopamine (DA) neurons. Profound alterations in
the homeostasis of the nigrostriatal DA system were induced by the absence of the
DAT. Extracellular levels of DA were elevated and clearance of released DA was
300-times slower than in control mice. This was accompanied by a 20-fold decrease
in tissue DA levels and a paradoxical doubling of the rate of DA synthesis. A
crucial role is indicated for the DAT in maintenance of DA neuron presynaptic
function, particularly in the control of storage mechanisms.
PMID- 9651513
TI - Neuropeptide Y: some viewpoints on a multifaceted peptide in the normal and
diseased nervous system.
AB - Using immunohistochemical and in situ hybridization methodologies the
localization of neuropeptide tyrosine (NPY) and two of its receptors, the Y1- and
the Y2-receptor (R), has been analysed in various tissues in normal animals and
animals subjected to different experimental procedures as well as animals with a
genetic and an acquired disease. (1) Dorsal root ganglion (DRG) neurons are
discussed with special focus on the effect of peripheral nerve injury. In normal
DRG neurons NPY cannot be detected, whereas Y1-R mRNA and Y1-R-like
immunoreactivity (LI) are strongly expressed. The Y1-Rs decorate the membrane of
the cell soma and are not transported peripherally into the axonal branches. Y2-R
mRNA levels are low. After axotomy there is a marked increase in NPY, a decrease
in Y1-Rs and an increase in Y2-Rs. The Y2-R is transported centrifugally. These
findings suggest that NPY-ergic mechanisms participate in the adaptive changes of
sensory neurons in response to injury. (2) Using specific antibodies the cellular
and subcellular localization of the Y1-R protein have been analysed in cerebral
blood vessels. The results demonstrate high concentrations of receptors in smooth
muscle cells around pial arterioles with lower numbers in large vessels on the
basal surface of the brain. In many regions the receptors 'disappear' after the
arterioles have entered the brain tissue. At the ultrastructural level the
receptors are found both on the endothelial and peripheral side of the muscle
cells as well as laterally, where muscle cells oppose each other. The receptor
protein is often associated with small vesicles. No NPY-positive nerve fibers
were found around the Y1-R-rich arterioles, but they were only seen around the
arteries with low Y1-R levels. The Y1-R-rich arterioles were, however, seen close
to numerous NPY-positive fibers originating from central interneurons. These
findings raise the possibility that centrally originating NPY can influence
cerebral blood flow, possibly by stimulating NPY-Rs on the peripheral side of the
muscle cells. However, also blood borne NPY, released under special conditions,
such as stress from sympathetic nerves and the adrenal medulla and transported
with blood, may stimulate receptors on the endothelial side of the smooth muscle
cells. (3) In the arcuate nucleus Y1- and Y2-Rs are found, whereby the Y1-Rs are
located in its ventro-medial portion and co-localized with POMC peptides, and the
Y2-R in its ventromedial part, partly co-localized with NPY. NPY nerve endings
makes synaptic contact with the POMC/Y1-R-positive neurons. In a mouse model for
genetic anorexia very high levels of NPY were observed in arcuate neurons as
compared to control mice. However, NPY mRNA levels were not different between the
two groups. Taken together these findings are in good agreement with the view
that NPY in the arcuate nucleus plays an important role in regulating feeding
behaviour. (4) After intracerebral prion inoculation in mice an upregulation of
NPY mRNA levels was observed in CA3 pyramidal neurons, and this effect was seen
at a time point just before the first behavioural symptoms were manifested. At
approximately the same time there was a dramatic decrease in Y2-R binding in
strata oriens and radiatum of the CA1 region of the hippocampus, whereas in other
regions no changes or much smaller changes were observed. Also, there was only a
very slight decrease in Y2-R mRNA levels in CA3 neurons. It thus appears as if
the prion disease prevents ligand binding to the Y2-R, perhaps by influencing
traffic of receptor proteins, possibly at the level of cell membrane-associated
caveolae, which have been implicated in the conversion of normal protein to
scrapie protein. It is possible that these changes in NPY-ergic mechanisms may
underlie some of the central symptoms associated with the prion disease.
(ABSTRACT TRUNCATED)
PMID- 9651514
TI - Sequence comparisons and functional studies of the proximal promoter of the
carbonic anhydrase 3 (CA3) gene.
AB - Carbonic anhydrase 3 (CA3) is a member of a gene family encoding proteins which
catalyse the hydration of CO2 to generate protons and bicarbonate ions for
cellular ion transport and pH homeostasis. In mouse embryos CA3 is expressed at
high levels in notochord and skeletal muscle and here we demonstrate that this
pattern of expression is the same in the developing human embryo. To investigate
mechanisms controlling CA3 transcription, we have isolated and compared 2.8kb of
sequence flanking exon 1 from the mouse and human genes. Several segments of high
sequence identity >80% have been identified, the longest segments of which
represent a proximal promoter region and a putative enhancer element. We have
shown previously that in cultured cells the human 2.8kb promoter region imposes
high level myogenic specific transcription of a reporter gene. However, we now
show that while this promoter region directed muscle-specific expression in
transgenic mouse embryos this was subject to position effects.
PMID- 9651515
TI - Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is expressed
in the anterior embryonic shield and the developing eye.
AB - The conserved transcription factor Pax6 is essential for eye development in
Drosophila and mammals (Hill, R.E., Favor, J., Hogan, B.L.M., Ton, C.C.T.,
Saunders, G.F., Hanson, I.M., Prosser, J., Jordan, T., Hastie, N.D., van
Heyningen, V., 1991. Mouse small eye results from mutations in a paired-like
homeobox containing gene. Nature 354, 522-525; Ton, C., Hirvonen, H., Miwa, H.,
Weil, M., Monaghan, P., Jordan, T., van Heyningen, V., Hastie, N., Meijers
Heijboer, H., Drechsler, M., Royer-Pokora, B., Collins, F., Swaroop, A., Strong,
L.C., Saunders, G.F., 1991. Positional cloning and characterization of a paired
box- and homeobox-containing gene from the aniridia region. Cell 6, 1059-1074;
Matsuo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, H., Koyama, E., Myokai, F.,
Matsuo, N., Toniguchi, S., Dari, H., Jseki, S., Ninomiya, Y., Fujiwara, M.,
Watanabe, T., Eto, K., 1993. A mutation at the Pax-6 gene in rat small eye is
associated with impaired migration of midbrain crest cells. Nature genet. 3, 299
304; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the
eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans.
Science 265, 785-789). These findings led to the hypothesis that additional genes
involved in invertebrate and vertebrate eye development are structurally and
functionally conserved (Halder, G., Callaerts, P., Gehring, W.J., 1995. New
perspectives on eye evolution. Curr. Opin. Gen. Dev. 5, 602-609; Quiring, R.,
Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of
Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785
789). Candidates for such conserved genes are the Drosophila homeobox gene sine
oculis (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V.,
Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain
containing protein required for the development of the entire visual system.
Neuron l2, 977-996) and its murine homologue Six3 (Oliver, G., Mailhos, A., Wehr,
R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of
the sine oculis gene, demarcates the most anterior border of the developing
neural plate and is expressed during eye development. Development 121, 4045
4055). sine oculis (so) is essential for the development of the larval and adult
visual system (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H.,
Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a
homeodomain-containing protein required for the development of the entire visual
system. Neuron l2, 977-996). Six3 is expressed in the anterior neural plate and
optic vesicles, lens, olfactory placodes and ventral forebrain (Oliver, G.,
Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a
murine homologue of the sine oculis gene, demarcates the most anterior border of
the developing neural plate and is expressed during eye development. Development
121, 4045-4055). Overexpression of mouse Six3 gene in medaka fish embryos
(Orvzias latipes) results in the formation of an ectopic lens, indicating that
Six3 activity can trigger the genetic pathway leading to lens formation (Oliver,
G., Loosli, F., Koster, R., Wittbrodt, J., Gruss, P., 1996. Ectopic lens
induction in fish in response to the murine homeobox gene Six3. Mech. Dev. 60,
233-239). We isolated the medaka Six3 homologue and analyzed its expression
pattern in the medaka embryo. It is expressed initially in the anterior embryonic
shield and later in the developing eye and prosencephalon. The early localized
expression of Six3 suggests a role in the regionalization of the rostral head.
PMID- 9651516
TI - Expression of T-box genes Tbx2-Tbx5 during chick organogenesis.
AB - T-box genes encode putative transcription factors implicated in diverse
developmental processes (Papaioannou, V.E. and Silver, L.M., 1998. BioEssays 20,
9-19). We have previously reported the embryonic expression patterns of T-box
genes in mice (Chapman, D.L., Garvey, N., Hancock, S., Alexiou, M., Agulnik,
S.I., Gibson-Brown, J.J., Cebra-Thomas, J., Bollag, R.J., Silver, L.M.,
Papaioannou, V.E., 1996. Dev. Dyn. 206, 379-390; Chapman, D.L., Agulnik, I.,
Hancock, S., Silver, L.M. and Papaioannou, V.E., 1996. Dev. Biol. 180, 534-542;
Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N.,
Silver, L.M., Papaioannou, V.E., 1996. Mech. Dev. 56, 93-101). Four of these
genes (Tbx2-Tbx5) are represented in the mouse genome as two cognate, linked gene
pairs (Agulnik, S.I., Garvey, N., Hancock, S., Ruvinsky, I., Chapman, D.L.,
Agulnik, I., Bollag, R., Papaioannou, V.E., Silver, L.M., 1996. Genetics 144, 249
254), and have all been implicated in playing important roles in limb development
(Gibson-Brown, J.J., Agulnik, S.I., Chapman, D.L., Alexiou, M., Garvey, N.,
Silver, L.M., Papaioannou, V.E., 1996. Mech. Dev. 56, 93-101). To investigate the
role of these genes in limb development, we cloned the chicken orthologs and
report functional studies, as well as patterns of expression in the developing
limbs, elsewhere (Gibson-Brown, J.J., Agulnik, S.I., Silver, L.M., Niswander, L.,
Papaioannou, V.E., Development, in press). This report details the patterns of
expression of Tbx2-Tbx5 in chick embryonic tissues other than the limbs.
PMID- 9651517
TI - Chromatin structure and functional analysis of the mouse HNF3alpha gene.
AB - The transcription factor HNF3alpha is a member of the winged-helix family of
regulatory proteins. It is expressed in the definitive endoderm, notochord, and
neural tube in embryos, but in the adult is expressed primarily in endoderm
derived tissues such as liver, lung, and pancreas. We present here the cloning of
the mouse HNF3alpha gene and a characterization of its chromatin structure and
regulatory sequences. The HNF3alpha gene is encoded by two exons and its
transcription initiates at multiple start sites at a TATA-less promoter that is
highly conserved between mouse and rat. We found different patterns of DNaseI
hypersensitive sites in HNF3alpha gene chromatin in different adult tissues in
which HNF3alpha is expressed, suggesting distinct regulatory mechanisms occurring
within different tissue derivatives of the endoderm germ layer. Cell transfection
data indicate that sequences spanning certain upstream hypersensitive sites can
enhance transcription from the HNF3alpha promoter, but only when stably
integrated into chromatin and not when transiently transfected. The results
suggest a complex regulatory interplay between distinct genetic regulatory
sequences that function specifically in chromatin.
PMID- 9651518
TI - Nitric oxide and carbon monoxide: parallel roles as neural messengers.
AB - Nitric oxide is now appreciated to be a molecule with important signaling
functions in the body. The purification and cloning of the first NO synthesizing
enzyme, NO synthase (NOS), from brain has led to the characterization of the
roles of NO in normal physiology and in pathogenic states. NO synthesis is
regulated in a complex manner, involving the association of activatory and
inhibitory proteins. The body appears to use at least one other, highly related
gas in a signaling function, carbon monoxide (CO). The enzyme responsible for CO
biosynthesis in brain, heme oxygenase-2 (HO2), is rapidly regulated by
neurotransmitter stimulation. The role for CO as neurotransmitter is suggested by
the altered intestinal motility in mice harboring a genomic deletion of HO2.
PMID- 9651519
TI - Immunohistochemical analysis of the expression of two serine-threonine kinases in
the maturing mouse testis.
AB - Previously we identified two intronless serine-threonine kinase genes (Tsk1 and
Tsk2) located 3 kb apart on mouse chromosome 16 (Galili, N., Baldwin, H.S., Lund,
J., Reeves, R., Gong, W., Wang, Z., Roe, B.A., Emanuel, B.S., Nayak, S.,
Mickanin, C., Budraf, M.L., Buck, C.A., 1997. A region of mouse chromosome 16 is
syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region. Gen.
Res. 7, 17-26). Tsk1 was identical to a putative testicular kinase reported by
Bielke et al. (Bielke, W., Blaschke, R.J., Miescher, G.C., Zurcher, G., Andres,
A.C., Ziemiecki, A., 1994. Characterization of a novel murine testis-specific
serine/threonine kinase. Gene 13, 235-239). Here we document the expression
patterns of each Tsk throughout spermiogenesis showing an initial association of
Tsk1 with cells in meiotic metaphase and a later association of Tsk2 with tail
like structures in the lumen of the seminiferous tubule.
PMID- 9651520
TI - Comparison of the expression of three highly related genes, Fgf8, Fgf17 and
Fgf18, in the mouse embryo.
AB - In mammals, 16 members of the Fgf family have so far been described with diverse
roles in embryonic cell growth and differentiation. Here, we report the
expression from early streak stage to midgestation of two newly-identified murine
genes, Fgf17 and Fgf18, that are most closely related to Fgf8 (63.7% and 56.8%
identical, respectively, at the amino acid level). Fgf17 is expressed during
gastrulation but at lower levels than Fgf8, while Fgf18 RNA is not expressed
until later, in paraxial mesoderm. In the developing tail bud, each Fgf gene
shows a different pattern of transcription. Distinct and overlapping expression
patterns are also described in the developing brain and limbs.
PMID- 9651521
TI - Gap junction wiring: a 'new' principle in cell-to-cell communication in the
nervous system?
AB - This review gives an updated excerpt of recent advances in our understanding of
brain gap junctions. It starts with a brief description of the principle
molecular composition of gap junctions before specific issues concerning brain
tissues are addressed. The following questions and matters are subjected to a
detailed analysis: First, why are there so many gap junctions in the brain?
Second, what is the functional significance of the cellular diversity of brain
gap junctions? Third, how do astrocytic gap junctions mediate intercellular
volume transmission (IVT), and what does IVT mean for glial-neuronal interaction?
Fourth, how frequent are interneuronal gap junctions; and what is their
functional significance in brain development and in interrelated chemical
electrotonic transmission at mixed synapses.
PMID- 9651522
TI - Mouse submandibular gland mucin: embryo-specific mRNA and protein species.
AB - Mouse submandibular salivary gland (SMG) mucin is the primary
histodifferentiation product of submandibular epithelia. We demonstrate marked
differences between embryonic, neonatal, and adult SMG mucin mRNA and protein by
Northern and Western blot analyses: E17 and 1-day-old neonates exhibit two unique
mucin transcripts (1.20 and 0.85 kb) which are approximately 19% greater or
smaller in size than the single (1.01 kb) adult transcript. Two embryonic protein
isoforms (Mr approximately 110 and 152 kDa) are immunodetected compared to a
single adult protein (Mr approximately 136 kDa), with the larger (approximately
152 kDa) embryonic isoform persisting in neonatal glands. Mucin transcripts are
localized to the branching epithelia in E14 and older SMGs, with increased
hybridization signal being seen in terminal bud and proacinar epithelial cells
with age; a significant 26% increase in transcript levels is detected by RNase
protection assay between E14 and E19. By contrast, submandibular mucin protein is
not immunodetected until E17, being primarily immunolocalized to terminal bud and
proacinar epithelial cell membranes. Our data clearly shows that substantial
qualitative differences exist between embryonic and adult SMG mucin mRNA and
protein.
PMID- 9651523
TI - Intrinsic function of a neuronal network - a vertebrate central pattern
generator.
AB - The cellular bases of vertebrate locomotor behaviour is reviewed using the
lamprey as a model system. Forebrain and brainstem cell populations initiate
locomotor activity via reticulospinal fibers activating a spinal network
comprised of glutamatergic and glycinergic interneurons. The role of different
subtypes of Ca2+ channels, Ca2+ dependent K+ channels and voltage dependent NMDA
channels at the neuronal and network level is in focus as well as the effects of
different metabotropic, aminergic and peptidergic modulators that target these
ion channels. This is one of the few vertebrate networks that is understood at a
cellular level.
PMID- 9651524
TI - Highly restricted expression at the ectoderm-endoderm boundary of PIHbox 9, a sea
urchin homeobox gene related to the human HB9 gene.
AB - Characterisation of a sea urchin (P. lividus) homeobox gene PIHbox 9 is reported.
The homeodomain of PIHbox9 is 95% identical to the homeodomain of the human HB9
gene, indicating that the two genes are highly related. Temporal expression
analysis during sea urchin embryogenesis showed an absence of transcripts at
early cleavage stages. At late gastrula stage, transcripts were barely detectable
and reached the highest abundance at prism/early pluteus stages. By whole mount
in situ hybridisation we observed a highly restricted expression in a few cells
of the ectoderm-endoderm boundary of embryos at the prism stage. At pluteus
stages, expression of PIHbox 9 was confined around the anus.
PMID- 9651525
TI - Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2
transcription factor.
AB - Although the CBFA1 gene encodes an osteoblast-specific transcription factor that
regulates osteoblast differentiation, uncertainty exists about the organization
of its 5' end and the relevance of a novel N-terminal sequence identified in the
mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by
a previously unrecognized upstream exon, designated exon -1, which is highly
conserved in mouse, rat and human. In addition, two splice donor sites may be
utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences.
The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA
containing the unique Osf2 5' sequence, whereas a second donor splice site gives
rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the
human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame
and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most
exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather
than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in
the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is
not essential for functioning of the CBFA1 gene product. In addition, multiple
transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts
by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms
containing deletions of exons 1 and 4. Thus, the alternative use of transcription
start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with
possible differences in transactivation potentials.
PMID- 9651526
TI - MDM2 expression during mouse embryogenesis and the requirement of p53.
AB - We compared mouse embryonic expression of the MDM2 proto-oncogene, p21WAF1/CIP1
and their transcriptional regulator, p53. MDM2 expression is ubiquitous from 7.5
to 11.5 days post coitum (dpc) and more restricted from 12.5 dpc, with the
highest levels in the testes and neural tube. From 14.5 to 18.5 dpc, the nasal
respiratory epithelium expresses high levels of MDM2 RNA and protein and
p21WAF1/CIP1 RNA, in both wild type and p53 null embryos. MDM2 expression during
development is tissue-specific and, like p21WAF1/CIP1, is independent of p53.
MDM2 may have a developmental role after 6.5 dpc, when MDM2 null mice die (Jones,
S.N., Roe, A.E., Donehower, L.A., Bradley, A., 1995. Rescue of embryonic
lethality in Mdm2-deficient mice by absence of p53. Nature 378, 206-208; Montes
de Oca Luna, R., Wagner, D.S., Lozano, G., 1995. Rescue of early embryonic
lethality in mdm2-deficient mice by deletion of p53. Nature 378, 203-206).
PMID- 9651527
TI - Brain nicotinic receptors: structure and regulation, role in learning and
reinforcement.
AB - The introduction, in the late sixties, of the concepts and methods of molecular
biology to the study of the nervous system had a profound impact on the field,
primarily through the identification of its basic molecular components. These
structures include, for example, the elementary units of the synapse:
neurotransmitters, neuropeptides and their receptors, but also ionic channels,
intracellular second messengers and the relevant enzymes, cell surface adhesion
molecules, or growth and trophic factors [21,78,81, 52,79]. Attempts to establish
appropriate causal relationships between these molecular components, the actual
organisation of neural networks, and a defined behavior, nevertheless, still must
overcome many difficulties. A first problem is the recognition of the minimum
levels of organisation, from the molecular, cellular, or multicellular (circuit)
to the higher cognitive levels, that determine the given physiological and/or
behavioral performance under investigation. A common difficulty (and potential
source of errors of interpretation) is to relate a cognitive function to a
network organization which does not possess the required structural complexity
and vice-versa. Another problem is to distinguish, among the components of the
system, those which are actually necessary and those which, taken together,
suffice for a given behavior to take place. Identification of such a minimal set
of building blocks may receive decisive insights from the elaboration of neurally
plausible formal models that bring together, within a single and coherent
'artificial organism', the neuronal network, the circulating activity, and the
behavior they determine (see [42,43,45,72,30]). In this communication, we shall
attempt, still in a preliminary fashion, to bring together: (1) our recent
knowledge on the molecular biology of brain nicotinic receptors (nAChRs) and
their allosteric properties and (2) integrated behaviors, such as cognitive
learning, investigated for instance with delayed-response or passive avoidance
tasks that are likely to involve nAChRs in particular at the level of
reinforcement (or reward) mechanisms (see [18,29,135]).
PMID- 9651528
TI - Cloning of 5'-flanking region and a polymorphic CTT trinucleotide repeat within
5'-untranslated region of mouse R-type calcium channel alpha1-subunit (Cchra1)
gene, and its genetic mapping.
AB - The 5'-flanking region of the mouse R-type calcium channel (Cchra1) gene was
cloned, and a transcriptional start point (tsp) was determined by rapid
amplification of 5'-cDNA end (5'RACE) method. The putative promoter region of the
gene contained no obvious TATA or CCAAT element in the expected positions, but
multiple putative binding sites for transcriptional factors, such as Sp1, AP-1,
AP-2, AP-3, EGR-1, EGR-2, NF-kappaB and HIP1, were detected. We found the
existence of a tandem CTT trinucleotide repeat within the 5'-untranslated region
(UTR) of the gene, and its polymorphism between C57BL/6J and Mus spretus. Using
this polymorphism, the Cchra1 was mapped to the region of chromosome 1 where the
synteny to human chromosome 1q was conserved.
PMID- 9651529
TI - Eubacterial origin of nuclear genes for chloroplast and cytosolic glucose-6
phosphate isomerase from spinach: sampling eubacterial gene diversity in
eukaryotic chromosomes through symbiosis.
AB - Higher plants possess two distinct nuclear-encoded glucose-6-phosphate isomerase
(GPI) isoenzymes, a cytosolic enzmye of the Embden-Meyerhof pathway and a
chloroplast enzyme essential to storage and mobilization of carbohydrate fixed by
the Calvin cycle. We have purified spinach chloroplast GPI to homogeneity,
determined amino acid sequences from the active enzyme, and cloned cDNAs for
chloroplast and cytosolic GPI isoenzymes from spinach. Sequence comparisons
reveal three distantly related families of GPI genes that are non-uniformly
distributed among contemporary eubacteria and archaebacteria, suggesting that
ancient gene diversity existed for this glycolytic enzyme. Spinach chloroplast
GPI is much more similar to its homologue from the cyanobacterium Synechocystis
PCC6803 than it is to the enzyme from any other source, providing strong evidence
that the gene for chloroplast GPI was acquired by the nucleus via endosymbiotic
gene transfer from the cyanobacterial antecedants of chloroplasts. Eukaryotic
nuclear genes for cytosolic GPI are more similar to eubacterial than to
archaebacterial homologues, suggesting that these too were acquired by eukaryotes
from eubacteria, probably during the course of the endosymbiotic origin of
mitochondria. Chloroplast and cytosolic GPI provide evidence for a eubacterial
origin of yet another component of the eukaryotic glycolytic pathway.
PMID- 9651530
TI - Isolation of a novel metabolizing system enriched in phase-II enzymes for short
term genotoxicity bioassays.
AB - Murine S9 liver fractions isolated from mice fed 7.5 g kg-1 2(3)-tert-Butyl-4
hydroxyanisole (BHA) for 3 weeks were tested to determine: (a) the profile of
both phase-I and phase-II xenobiotic metabolizing enzymes; (b) their ability to
induce in vitro covalent binding of some precarcinogens to calf thymus DNA; and
(c) their activation in a standard genetic toxicology assay. With regard to phase
I pathway, the S9 fraction expressed various cytochrome P-450-(CYP) (classes 1A1,
1A2, 2B1, 2E1, and 3A)-dependent biotransformation enzymes at levels comparable
with those present in murine control liver. For post-oxidative enzymes, the S9
expressed high levels of glutathione S-transferases (up to 12-fold increase),
glutathione S-epoxide-transferase (up to 2.6-fold), UDP-glucuronosyl transferase
(up to 5.3-fold) and epoxide hydrolase (up to 2.6-fold) activities, as compared
to untreated mice. The in vitro DNA binding of the precarcinogenic agents [14C]
1,4-dichlorobenzene, [14C]-1,2-dichlorobenzene and [14C]-1,4-dibromobenzene,
mediated by BHA-induced cytosol and/or microsomal preparation, showed an increase
in specific activity comparable to that observed with phase-I (PB/beta NF)
induced S9. In some instances, covalent binding was even more elevated using the
BHA-induced systems as compared with traditional S9 fractions. For example,
cytosol derived from BHA-administered mice was able to induce a significant
binding to calf thymus DNA up to 26.2-fold increase for [14C]-1,4
dichlorobenzene, while cytosol from PB/beta NF was not. A high mutagenic response
on diploid D7 strain of Saccharomyces cerevisiae as exemplified by a marked
induction of mitotic gene conversion and point (reverse) mutation confirmed that
BHA-derived S9 fractions activate precarcinogens to final genotoxins. Because a
number of chemicals are activated by either oxidative or post-oxidative enzymes,
the use of metabolizing biosystems, with an enhanced phase-II pathway, together
with classical S9 fractions, can improve the sensitivity of the assay in
detecting unknown genotoxins.
PMID- 9651532
TI - RNA editing of brain glutamate receptor channels: mechanism and physiology.
AB - Glutamate-gated cation selective channels mediate fast excitatory
neurotransmission in the mammalian brain. Functionally critical channel positions
contain amino acid residues not predicted from the exonic sequence for the
channel subunits. The codons for these residues are created in the respective
primary gene transcripts by the site selective deamination of adenosine to
inosine. This type of RNA editing requires a short double-stranded RNA structure
formed by the exonic sequence around the adenosine targeted for deamination with
a complementary sequence in the downstream intron and hence, it precedes
splicing. Candidate enzymes for nuclear transcript editing currently comprise
three molecularly cloned mammalian RNA-dependent adenosine deaminases. Two of
these are expressed in most body tissues, perhaps indicating that adenosine
deamination in transcripts is more global than has been recognized. Indeed,
numerous mRNAs in different tissues may contain inosine residues and encode
proteins with amino acid substitutions and different properties relative to the
exonically encoded forms. If so, RNA editing by adenosine deamination may
significantly enlarge the functional repertoire of the mammalian genome.
PMID- 9651531
TI - Genomic organization and cloning of the human homologue of murine Sipa-1.
AB - Murine Sipa-1 (signal-induced proliferation associated protein) is a mitogen
induced GTPase activating protein (GAP). While mapping candidate genes for
multiple endocrine neoplasia type 1 (MEN1) at 11q13, we cloned the human
homologue of Sipa-1. Herein, we report the complete cDNA sequence, expression,
and genomic organization of SIPA-1. SIPA-1 consists of 16 exons with highly
conserved exon-intron boundaries. The predicted SIPA-1 protein is highly
homologous to the mouse protein, particularly in the region of the GAP-related
domain at the amino terminus and the leucine zipper at the carboxy terminus. It
is widely expressed, including in fetal tissues, but is most highly expressed in
lymphoid organs. During the course of cloning SIPA-1, the MEN1 gene was
identified, thus excluding human SIPA-1 as a candidate for this disease.
PMID- 9651533
TI - Development of new tester strains derived from E. coli WP2uvrA for the
determination of mutational specificity.
AB - We have developed a set of multipurpose tester strains (WP3101 to WP3106) derived
from E. coli WP2uvrA for the detection and classification of mutagens. Six kinds
of F' plasmid (lacI, lacZ, proAB+) in strains CC101-CC106, each of which carried
a different lacZ allele, were transferred to a delta(lac-pro) derivative of
WP2uvrA. Assays for transitions and transversions are based upon Lac+ reversion
of a specific mutation located within the lacZ gene on an F' plasmid in strains
WP3101-WP3106. In addition, the trpE65(ochre) allele in the same strains is
available for Trp+ reversion assays. Using the new tester strains, we
investigated the mutational specificities of various chemical mutagens. Base
analog mutagens and alkylating mutagens induced specific types of base
substitutions. G:C-->A:T transitions and G:C-->T:A transversions predominated in
mutagenesis induced by 4-nitroquinoline 1-oxide. Only a slight increase in G:C-
>T:A transversions was observed in cells treated with 2-(2-furyl)-3-(5-nitro-2
furyl)acrylamide (AF-2), although the potent mutagenicity of AF-2 was detected in
a concurrent Trp+ reversion assay in the same strain. Sodium azide, on the other
hand, was negative in the Trp+ reversion assay but specifically induced G:C-->A:T
transitions. Present finding suggested that target sites for AF-2- and azide
induced lesions may largely depend on sequence context.
PMID- 9651534
TI - Modulation of mitomycin C-induced sister chromatid exchanges and cell cycle delay
by buthionine sulfoximine and reduced glutathione in mouse bone marrow cells in
vivo.
AB - Mitomycin C (MMC) is a bifunctional alkylating agent and a chemotherapeutic drug,
covalently binds to the DNA of cells and produces monoadducts and DNA-DNA, DNA
protein crosslinks, induces damages at chromosomal level and slows down the rate
of cell proliferation. Reduced glutathione (GSH), a major non-protein thiol
substance plays an important role in detoxification of cells against the toxic
effect of exogenous compounds. In order to understand the role of factor which
affects MMC sensitivity, we have made an attempt to establish a relationship
between MMC-induced DNA damages and the endogenous GSH-status of the cells. MMC
was treated to normal and buthionine sulfoximine (BSO; GSH-depleting agent)
treated mice. Exogenous GSH was also added to MMC-treated normal mice. Cells were
fixed at 24 h and sister chromatid exchanges (SCEs) and average generation time
(AGT) were scored. MMC-induced SCEs and cell cycle delay significantly with
respect to control and the frequency of SCEs was increased considerably while MMC
treatment combined with either GSH or BSO. The induction of cell cycle delay by
MMC was reduced significantly when GSH or BSO was present along with MMC. These
observations indicate that the factor responsible for inducing delay in cell
cycle after MMC treatment may not be relevant for SCE-induction.
PMID- 9651535
TI - Glutamate receptors: brain function and signal transduction.
AB - Glutamate receptors are important in neural plasticity, neural development and
neurodegeneration. N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors act as glutamate
gated cation channels, whereas metabotropic receptors (mGluRs) modulate the
production of second messengers via G proteins. Molecular studies from our and
other laboratories indicated that NMDA receptors and mGluRs exist as multiple
subunits (NMDAR1 and NMDAR2A-2D) and multiple subtypes (mGluR1-mGluR8). In light
of the molecular diversity of glutamate receptors, we explored the function and
intracellular signaling mechanisms of different members of glutamate receptors.
In the visual system, retinal bipolar cells receive glutamate transmission from
photoreceptors and contribute to segregating visual signals into ON and OFF
pathways. The molecularly cloned mGluR6 is restrictedly expressed at the
postsynaptic site of ON-bipolar cells in both rod and cone systems. Gene
targeting of mGluR6 results in a loss of ON responses without changing OFF
responses and severely impairs detecting visual contrasts. Since AMPA receptors
mediate OFF responses in OFF-bipolar cells, two distinct types of glutamate
receptors effectively operate for ON and OFF responses. mGluR1 and mGluR5 are
both coupled to inositol triphosphate (IP3)/calcium signal transduction with an
identical agonist selectivity. Single-cell intracellular calcium ([Ca2+]i)
recordings indicated that glutamate evokes a non-oscillatory and oscillatory
[Ca2+]i response in mGluR1-expressing and mGluR5-expressing cells, respectively.
This difference results from a single amino acid substitution, aspartate of
mGluR1 or threonine of mGluR5, at the G protein-interacting carboxy-terminal
domains. Protein kinase C phosphorylation of the threonine of mGluR5 is
responsible for inducing [Ca2+]i oscillations in mGluR5-expressing cells and
cultured glial cells. Thus, the two closely related mGluR subtypes mediate
diverging intracellular signaling in glutamate transmission.
PMID- 9651536
TI - Caged amphibian tadpoles and in situ genotoxicity monitoring of aquatic
environments with the alkaline single cell gel electrophoresis (comet) assay.
AB - In previous studies we demonstrated that indigenous amphibian tadpoles are
suitable organisms for monitoring small bodies of water (e.g., creeks, ponds, and
drainage ditches) using the alkaline single cell gel electrophoresis (SCG) or
'comet' assay. This approach involves detection, under alkaline conditions, of
cell DNA fragments which on electrophoresis migrate from the nuclear core,
resulting in a 'comet with tail' formation. However, although often plentiful,
tadpoles are not present in all aquatic environments. Both larger bodies of water
(e.g., lakes and rivers) and those impacted upon heavily by man (e.g., bodies of
water near industrial sites, on landfills, and in urban areas) often do not
support amphibian tadpole populations. An alternative approach to the collection
of indigenous tadpoles is to place caged tadpoles at these sites for short term
exposures to environmental contaminants. To determine the feasibility of such an
approach, Rana clamitans (green frog) and Bufo americanus (American toad)
tadpoles were housed in cages at 11 sites in southwestern Ontario (Canada). In a
preliminary experiment, we found that tadpoles caged at a polluted reference site
(Tallgrass Prairie Heritage Park in Windsor, Ontario) for either 7 or 14 days
showed significant (P < 0.05) increases in DNA damage, relative to tadpoles caged
in the laboratory in dechlorinated water. As a result we routinely used a 7 day
exposure time. Significantly (P < 0.05) increased levels of DNA damage, relative
to their controls, were observed in tadpoles caged at three sites along two
creeks draining a large petrochemical installation south of Sarnia, Ontario; at
two sites in the Tallgrass Prairie Heritage Park; and at a site along the Ecarte
Channel which is part of the St. Clair River. The DNA damage levels of animals
caged in Lake St. Clair, in the Trenton Channel of the Detroit River, at a
landfill site, and in two creeks in the city of Windsor did not differ
significantly (P > 0.05) from their controls. This study demonstrates that caged
tadpoles are suitable for monitoring most bodies of fresh water, particularly
those aquatic habitats mentioned above where indigenous tadpoles are not present.
A combined approach of collecting indigenous tadpoles and using caged tadpoles
should provide a sensitive system for aquatic genotoxicity monitoring.
PMID- 9651537
TI - Functional implications of multiple dopamine receptor subtypes: the D1/D3
receptor coexistence.
AB - The D3 dopamine receptor, a D2-like receptor, is selectively expressed in the
ventral striatum, particularly in the shell of nucleus accumbens and islands of
Calleja, where it is found in medium sized substance P neurons. The latter co
express the D1 receptor whose interaction with the D3 receptor was studied by
treating rats with selective agonists and antagonists. In agreement with the
opposite cAMP response, they mediate in cultured neuroblastoma cells, the D1 and
D3 receptors exerted opposite influences on c-fos expression in islands of
Calleja. However, in agreement with the synergistic influence of cAMP on D3
receptor-mediated mitogenesis on the same cultured cells, D1 and D3 receptor
stimulation in vivo synergistically enhanced preprotachykinin mRNA in the shell
of accumbens. This indicates that the two receptor subtypes may affect neurons in
either synergy or opposition according to the cell or signal generated. Levodopa
induced behavioral sensitization in hemiparkinsonian rats is another example of
D1/D3 receptor interaction. Hence repeated levodopa administration induces the
ectopic appearance of the D3 receptor in substance P/dynorphin, striatonigral
neurons of the dorsal striatum. This induction is secondary to D1 receptor
stimulation in neurons of the denervated side and fully accounts for the
sensitization, i.e. the increased behavioral responsiveness to levodopa. During
brain development, a similar process could operate to control the late appearance
of the D3 receptor in D1-receptor bearing neurons of the ventral striatum at a
time at which they start to be innervated by dopamine neurons. Finally, taking
into account a variety of genetic, developmental, neuroimaging and
pharmacological data, we postulate that imbalances between the levels of D1 and
D3 receptors in the same neurons could be responsible for schizophrenic
disorders.
PMID- 9651538
TI - Signal transduction molecules at the glutamatergic postsynaptic membrane.
AB - We have applied techniques from modern molecular biology and biochemistry to
unravel the complex molecular structure of the postsynaptic membrane at
glutamatergic synapses in the central nervous system. We have characterized a set
of new proteins that are constituents of the postsynaptic density, including PSD
95, densin-180, citron (a rho/rac effector protein), and synaptic gp130 Ras GAP
(a new Ras GTPase-activating protein). The structure of PSD-95 revealed a new
protein motif, the PDZ domain, that plays an important role in the assembly of
signal transduction complexes at intercellular junctions. More recently, we have
used new imaging tools to observe the dynamics of autophosphorylation of CaM
kinase II in intact hippocampal tissue. We have been able to detect changes in
the amount of autophosphorylated CaM kinase II in dendrites, individual synapses,
and somas of hippocampal neurons following induction of long-term potentiation by
tetanic stimulation. In addition, we have observed a specific increase in the
concentration of CaM kinase II in dendrites of neurons receiving tetanic
stimulation. This increase appears to be the result of dendritic synthesis of new
protein. Over the next several years we will apply similar methods to study
regulatory changes that occur at the molecular level in glutamatergic synapses in
the CNS as the brain processes and stores new information.
PMID- 9651539
TI - Random population-wide genetic damage induced in replicating cells treated with
methotrexate.
AB - Low lethality treatment of the NIH 3T3 mouse cell line with methotrexate (MTX)
during exponential multiplication results in heterogeneous, heritable reduction
in growth rate of most if not all the replicatively surviving cells. The
effective concentrations of MTX are 10 to 100 times higher in molecular, cellular
and developmental biology medium 402 (MCDB 402) than in Dulbecco's modification
of Eagle's medium (DMEM) medium because of the folate-sparing presence of
adenine, thymidine and, particularly, of folinic acid in MCDB 402 medium. The
reduced growth rates are detectable during early passages of surviving
populations before the faster growing cells dominate them. The heritable effect
is most clearly demonstrated by sequestered cloning of many individual cells
immediately after drug treatment, and repeatedly measuring the growth rates of
the clones in serial passages. After 7-10 passages of the clones, there is an
increase in growth rate of some of the slow growing clones presumably due to the
generation and selection of faster growing cells. Evidence from mutagenic studies
at a single genetic locus in other cell lines suggests that heritable reductions
in growth rate arise from chromosome aberrations although point mutations may
also contribute to the effect. Clastogenic changes can be induced by a wide
variety of mutagens and carcinogens, many of which are used in chemotherapy of
cancer and other chronic diseases. The population-wide, heritable damage to cells
may be the source of, or may contribute to, late-occurring side effects of
treatment in cancer and other chronic diseases.
PMID- 9651540
TI - Integrated events in central dopamine transmission as analyzed at multiple
levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine
A1/dopamine D1 receptor interactions in the basal ganglia.
AB - An analysis at the network and membrane level has provided evidence that
antagonistic interactions between adenosine A2A/dopamine D2 and adenosine
A1/dopamine D1 receptors in the ventral and dorsal striatum are at least in part
responsible for the motor stimulant effects of adenosine receptor antagonists
like caffeine and for the motor depressant actions of adenosine receptor
agonists. The results obtained in stably cotransfected cells also underline the
hypothesis that the intramembrane A2A/D2 and A1/D1 receptor interactions
represent functionally important mechanisms that may be the major mechanism for
the demonstrated antagonistic A2A/D2 and A1/D1 receptor interactions found in
vivo in behavioural studies and in studies on in vivo microdialysis of the
striopallidal and strioentopeduncular GABAergic pathways. A major mechanism for
the direct intramembrane A2A/D2 and A1/D1 receptor interactions may involve
formation of A2A/D2 and A1/D1 heterodimers leading to allosteric changes that
will alter the affinity as well as the G protein coupling and thus the efficacy
to control the target proteins in the membranes. This is the first molecular
network to cellular integration in the nerve cell membrane and may be well suited
for a number of integrated tasks and can be performed in a short-time scale, in
comparison with the very long-time scale observed when receptor heteroregulation
involves phosphorylation or receptor resynthesis. Multiple receptor-receptor
interactions within the membranes through formation of receptor clusters may lead
to the storage of information within the membranes. Such molecular circuits can
represent hidden layers within the membranes that substantially increase the
computational potential of neuronal networks. These molecular circuits are biased
and may therefore represent part of the molecular mechanism for the storage of
memory traces (engrams) in the membranes.
PMID- 9651541
TI - Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and
chloral hydrate in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells.
AB - The disinfection of water, required to make it safe for human consumption, leads
to the presence of halogenated organic compounds. Three of these carcinogenic
'disinfection by-products', dichloroacetic acid (DCA), trichloroacetic acid (TCA)
and chloral hydrate (CH) have been widely evaluated for their potential toxicity.
The mechanism(s) by which they exert their activity and the steps in the etiology
of the cancers that they induce are important pieces of information that are
required to develop valid biologically-based quantitative models for risk
assessment. Determining whether these chemicals induce tumors by genotoxic or
nongenotoxic mechanisms (or a combination of both) is key to this evaluation. We
evaluated these three chemicals for their potential to induce micronuclei and
aberrations as well as mutations in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells.
TCA was mutagenic (only with S9 activation) and is one of the least potent
mutagens that we have evaluated. Likewise, CH was a very weak mutagen. DCA was
weakly mutagenic, with a potency (no. of induced mutants/microgram of chemical)
similar to (but less than) ethylmethanesulfonate (EMS), a classic mutagen. When
our information is combined with that from other studies, it seems reasonable to
postulate that mutational events are involved in the etiology of the observed
mouse liver tumors induced by DCA at drinking water doses of 0.5 to 3.5 g/l, and
perhaps chloral hydrate at a drinking water dose of 1 g/l. The weight-of-evidence
for TCA suggest that it is less likely to be a mutagenic carcinogen. However,
given the fact that DCA is a weak mutagen in the present and all of the published
studies, it seems unlikely that it would be mutagenic (or possibly carcinogenic)
at the levels seen in finished drinking water.
PMID- 9651542
TI - The DARPP-32/protein phosphatase-1 cascade: a model for signal integration.
PMID- 9651543
TI - Determination of diesel genotoxicity in firebreathers by micronuclei and nuclear
abnormalities in buccal mucosa.
AB - Diesel or its derivatives could have aneuploidogenic and/or clastogenic activity.
Hence, the genotoxicity of diesel gases has been studied, considering exposure to
them as potentially carcinogenic. The results obtained by different authors
suggest the need to know the effects of direct and chronic exposure to diesel in
humans, as in the case of the street workers called 'firebreathers' who fill
their buccal cavity with diesel and then spread it to a burning torch many times
during the day in order to give a 'dragon show' for 5 h a day and 6 days a week.
The buccal samples of eight firebreathers were collected, processed and scored
according to the criterion established by Tolbert et al., 1992 and then compared
with positive and negative control groups. The results revealed that diesel was
not micronucleogenic although it induces some nuclear abnormalities.
PMID- 9651544
TI - Role of reelin in the control of brain development.
AB - Reeler is an autosomal recessive mutation in mice that results in widespread
disruption of laminated regions of the brain. We isolated a gene, reelin, that is
mutated in reeler mice. The protein product of reelin has features of
extracellular matrix components and it is expressed in a temporal and spatial
pattern during embryonic and postnatal development consistent with the phenotypic
defects in reeler mice. To understand the molecular basis of the function of
Reelin, we constructed a full length reelin clone and used it to direct Reelin
expression. Using this clone we found that Reelin is a secreted glycoprotein and
that a highly charged C-terminal region is essential for secretion. Furthermore,
we demonstrated that an amino acid sequence present in the N-terminal region of
Reelin contains an epitope that is recognized by the CR-50 monoclonal antibody.
CR-50 was raised against an antigen expressed in normal mouse brain that is
absent in reeler mice. The interaction of CR-50 with its epitope has been shown
to disrupt neuronal migration in vitro and in vivo. We used CR-50 to precipitate
p385 Reelin from reticulocyte extracts programmed with reelin mRNA, from cells
transfected with reelin clones and from cerebellar explants. Reelin appears to
function as an instructive signal in the regulation of cell patterning during
development.
PMID- 9651545
TI - Neurotrophin receptors: mediators of life and death.
AB - The mechanism of action of NGF has continued to provide a challenging and
formidable problem in signal transduction. NGF can bind independently to two
different receptors, the trkA tyrosine kinase receptor and the p75 neurotrophin
receptor, which are involved in many different signaling events. In addition to
promoting cell differentiation survival, NGF can paradoxically be an inducer of
cell death. Several receptor mediated mechanisms are proposed to explain how NGF
might act as a trophic factor and as a cell killer. The survival and cell death
properties of the receptors are dependent upon the relative ratio of receptors
and the persistent nature of the signaling events.
PMID- 9651546
TI - On CNS repair and protection strategies: novel approaches with implications for
spinal cord injury and Parkinson's disease.
AB - In the adult mammalian central nervous system lost nerve cells are not replaced
and there is no regeneration of injured axons in white matter. Together, these
two facts mean that there are no spontaneous reparative mechanisms in operation.
Instead, the adult central nervous system copes with the risks of injuries and
diseases by protective encapsulation in bone, by a multitude of neuroprotective
mechanisms, and finally by the fact that many important functions are represented
by a much larger number of neurons than minimally needed. The long life
expectancy of a human being nevertheless means that the risk that the central
nervous system is affected by disease, injury or other forms of insults for which
it cannot fully compensate is relatively high. Experimentally, two strategies are
being pursued in order to develop ways of minimizing various forms of CNS damage,
namely neuroprotective and reparative strategies. Here we present a possible
reparative intervention applicable to spinal cord injury based on multiple white
to-gray matter peripheral nerve bridge grafts and work based on the specific role
of Nurr1 for dopamine neuron development, suggesting that development of ligands
to transcription factor might be a new inroad to neuroprotective treatments in
Parkinson's disease.
PMID- 9651547
TI - Interleukin-1 receptors: cloning studies and role in central nervous system
disorders.
PMID- 9651548
TI - Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine
function.
AB - The cytokines are a large and diverse family of polypeptide regulators with
multiple regulatory functions that have been comprehensively evaluated in the
immune system under strictly controlled experimental conditions. These peptide
signals exhibit often unpredictable interactions when evaluated for their
pathophysiological involvement in specific inflammatory conditions in vivo. In
our joint efforts to understand the basis for early pathophysiological changes in
the brains of HIV-infected subjects, we have developed animal models for
lentivirus infections, and assessed the actions of various cytokines acutely on
transmitter release properties in vitro, and in an in vivo transgenic mouse
model. IL1beta, IL2, IL6, and IFNalpha will each enhance the release of AVP in
slices of rat hypothalamus and amygdala. TGFbeta selectively blocks the ability
of ACh to release AVP from hypothalamus or amygdala, but has no effects on the
release stimulated by other cytokines. IFNalpha, but not TGFbeta will also
activate CRH release; as with AVP, TGF selectively blocks the ACh-stimulated CRH
release in both amygdala and hypothalamus. The IFNalpha-stimulated release of AVP
and CRH appears to be mediated by cyclic GMP production, and this release by
IFNalpha and IL-2 may be mediated in part by activation of constitutive nitric
oxide synthase. These combined in vitro actions would suggest that cns cytokine
actions should upregulate the hypothalamic pituitary adrenal axis. In a
transgenic mouse model with increased astrocytic expression and release of the
cytokine IL6, the HPA axis is upregulated, but the effect seems attributable to
adrenocortical hypersensitization to ACTH. Lastly, in studies of cytokine
mediated effects on astrocytic uptake of the excitatory transmitter glutamate,
the reactive oxygen species hydrogen peroxide and peroxynitrite, but not nitric
oxide, inhibited glutamate uptake in a concentration-dependent manner. Although
superoxide and nitric oxide had no effect by themselves on the rate of glutamate
uptake by astrocytes, the same cultures did respond to nitric oxide with a
sustained increase in cytoplasmic free calcium. Thus while reactive oxygen
species do provide a potential path to neurotoxicity but one apparently not
involving nitric oxide. These various data provide important opportunities for
early therapeutic interventions in neuro-inflammatory states such as Neuro-AIDS.
PMID- 9651549
TI - Transgenic mice and cytokine actions in the brain: bridging the gap between
structural and functional neuropathology.
AB - Deciphering the neurobiological consequences of cerebral cytokine expression in
vivo represents an important research objective which has implications for our
understanding of the pathogenesis and treatment of many significant neurological
disorders. In our own pursuit of this objective, studies by us have utilized a
transgenic strategy employing the GFAP promoter to direct the chronic expression
of the cytokines IL-3, IL-6, IFN-alpha or TNF-alpha to astrocytes in mice.
Transgenic expression of each cytokine produces a unique spectrum of
neuropathological and functional alterations, thereby directly implicating these
mediators in the pathogenesis of CNS disease. Moreover, as exemplified here with
the GFAP-IL6 transgenic mice, these models are valuable tools in which to perform
multi-level analysis to link molecular and cellular alterations to specific
electrophysiological, neuroendocrine and behavioral outcomes. Integrative studies
such as described here in the GFAP-cytokine transgenic mice, are providing a more
thorough understanding of the actions of cytokines in the CNS and bridge the gap
between structural and functional neuropathology.
PMID- 9651550
TI - Gene regulation of cell adhesion: a key step in neural morphogenesis.
AB - A mounting body of evidence suggests that cell adhesion molecules (CAMs) play
important roles in morphogenetic patterning of the nervous system. The combined
factors that control the expression of CAMs during early neural development are,
however, largely unknown. We have hypothesized that the coordinate expression of
homeobox (Hox) and paired box (Pax) proteins in the neural axis leads to the
differential expression of particular CAM genes. Following this hypothesis, we
have characterized the promoters and identified cis-regulatory sequences that
bind to and respond to Hox and Pax proteins in the genes for three neurally
expressed CAMs - the neural cell adhesion molecule, N-CAM, the neuron-glia cell
adhesion molecule, Ng-CAM, and L1. Experiments on transgenic mice carrying N-CAM
promoter/lacZ reporter gene constructs indicated that mutation of either the HBS
or the PBS disrupted patterning of N-CAM expression in the embryonic spinal cord.
To examine the factors that restrict the expression of certain CAMs to the
nervous system, we identified regulatory elements that block expression of the Ng
CAM and L1 genes in non-neural cells. We characterized a 310 base pair region of
the first intron of the Ng-CAM gene containing five neural restrictive silencer
elements (NRSEs) and a binding site for the Pax-3 protein. These elements
silenced activity of the Ng-CAM promoter in NIH3T3 fibroblasts, but had no effect
on its activity in N2A neuroblastoma cells line. Similar analyses of the L1 gene
revealed a single NRSE within the second intron that was important for silencing
in this cellular transfection system. To analyze the role of the NRSE in vivo, we
prepared transgenic mice containing two L1 gene/lacZ constructs, one containing
the NRSE and another in which the NRSE was deleted. The wild type L1lacZ
transgene showed a neurally restricted pattern of expression, whereas the NRSE
mutated L1 construct showed extensive extraneural expression of the L1 gene.
Thus, neural specificity of CAM expression is controlled by the NRSE. The general
significance of these observations is that they connect the expression of
important families of transcriptional regulators with gene products capable of
direct cellular mechanochemistry.
PMID- 9651551
TI - Long-term potentiation and spatial training are both associated with the
generation of new excitatory synapses.
PMID- 9651553
TI - How to study consciousness scientifically.
PMID- 9651552
TI - Positive and negative regulatory mechanisms that mediate long-term memory
storage.
AB - The protein kinase A pathway and the cyclic AMP-response element binding protein
(CREB) appear to play a critical role in the consolidation of short-term changes
in neuronal activity into long-term memory storage in a variety of systems
ranging from the gill and siphon withdrawal reflex in Aplysia to olfactory
conditioning in Drosophila to spatial and contextual learning in mice. In this
review we describe the molecular machinery that mediates memory consolidation in
each of these systems. One of the surprising findings to emerge, particularly
from studies of long-term facilitation in Aplysia, is that memory storage is
mediated by not only positive but also negative regulatory mechanisms, in much
the same way as cell division is controlled by the proteins encoded by oncogenes
and tumor suppressor genes. This suggests the interesting possibility that there
are memory suppressor genes whose protein products impede memory storage.
PMID- 9651554
TI - Do genetic determinates of ischaemic heart disease imply that prevention may
become more difficult?
AB - Favourable changes in environment and lifestyle in the community may lead to a
situation in which genetic determinants of ischaemic heart disease assume greater
importance. Does this imply that ischaemic heart disease becomes more difficult
to prevent? Much of the role of the family history as a risk factor within
populations may be explained by new genetic mutations. However, differences
between populations are generally attributable to environmental differences. A
model of gene-environment interaction implies that individuals or populations
with genetic risk markers are both more susceptible and more responsive to
environmental changes, including lifestyle and drugs, and thus, may be eminently
treatable.
PMID- 9651555
TI - Metabolic features of inflammatory bowel disease in a remission phase of the
disease activity.
AB - OBJECTIVES: To evaluate the anthropometric and metabolic characteristics of
patients with Crohn's disease (CD) and ulcerative colitis (UC), comparing both
groups with healthy volunteers. DESIGN: A cross-sectional study. SETTING: The
Department of Internal Medicine, Catholic University Hospital, Rome, Italy.
SUBJECTS: Thirty-four patients with biopsy-proven inflammatory bowel disease (18
CD; 16 UC) in clinical remission (SCDAI < 3 and Powell-Tuck index < 4) not
receiving steroid therapy. INTERVENTIONS: All patients had a clinical
examination. MAIN OUTCOME MEASURES: Blood indicators of inflammation and
nutritional status. Body composition was assessed by both anthropometry and
bioimpedance and metabolic variables were measured by indirect calorimetry over a
60-90 min period. RESULTS: CD had a lower body weight than both controls (58.1
kg, range 41.5-71.0 vs. 66.4 kg, range 57.0-76.0; P < 0.001) and UC) 58.1 kg,
range 41.5-71.0 vs. 69.6 kg, range 50.5-94.0; (P < 0.001). Fat-free mass (FFM)
did not differ between the groups, whilst fat mass was significantly lower in CD
than in UC (P < 0.05) and controls (P < 0.001). Normalizing the basal metabolic
rate by FFM, a higher value was found in CD compared with UC (143 kJ kg-1) d-(
1), range 97.5-179 vs. 133 kJ kg-1 d-1, range 123-148; P < 0.05) and control
subject 143 kj kg-1 d-1, range 97.5-179 vs. 134 kj kg-1 d-1, range 122-162; P <
0.05). The nonprotein respiratory quotient was significantly lower in CD compared
to UC 0.80, range 0.73-0.84 vs. 0.84, range 0.79-0.91; P < 0.01) and controls
(0.80, range 0.73-0.84 vs. 0.83, range 0.81-0.87; P < 0.001), with a consequently
higher lipid oxidation rate in CD. CONCLUSIONS: CD subjects showed a decreased
fat mass and enhanced utilization of lipids compared with UC and controls. These
data could be explained by the larger intestinal involvement and considered as a
contribution to lipid tissue wasting in CD.
PMID- 9651556
TI - Dynamic assessment of parathyroid function in acute malaria.
AB - OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced,
sustained hypocalcaemia in patients with acute malaria and in healthy volunteers.
DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples
taken before and during a variable-rate tri-sodium citrate infusion designed to
'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below
baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with
acute malaria, four of whom were restudied in convalescence, and 12 healthy
controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and
serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium
was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/-
0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0
+/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium
concentrations were achieved more rapidly in the controls than the patients
(within 15 vs. 30 min) despite significantly more citrate being required in the
patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09
mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised
calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial
rate of fall of ionised calcium, was similar during the first 5 min of the clamp
(132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls,
respectively, P > 0.05), as were steady-state serum PTH levels during the second
hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal
ionised calcium levels but the lowest serum intact PTH levels before and during
the clamp, consistent with an increase in skeletal PTH sensitivity after
treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for
basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria.
Skeletal resistance may attenuate the effects of the PTH response but patients
with malaria appear relatively resistant to the calcium chelating effects of
citrated blood products.
PMID- 9651557
TI - Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in
men with combined hyperlipidaemia.
AB - OBJECTIVES: Gemfibrozil is the most widely used fibric acid for the management of
combined hyperlipidaemia. It has beneficial effects in the prevention of coronary
heart disease (CHD). The mechanisms by which it exerts this effect are not
completely resolved. We studied whether gemfibrozil affects low-density
lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate
combined hyperlipidaemia at high risk for progressive atherosclerosis. DESIGN:
Open treatment with 2 x 600 mg gemfibrozil daily for 12 weeks. SETTING:
Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Twenty-three
patients with combined hyperlipidaemia and CHD or a positive family history for
both CHD and hyperlipidaemia. MAIN OUTCOME MEASURES: Effects on triglyceride
(TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative
modification. RESULTS: During treatment with gemfibrozil, plasma TG concentration
decreased from 2.83 +/- 0.85 to 2.02 +/- 0.89 mmol L-1 (P < 0.001). All but one
patient were shown to have LDL pattern B. The LDL pattern did not change upon
treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime
during in-vitro oxidation slightly decreased from 105 +/- 22 to 99 +/- 18 min (P
= 0.01). The concentration of autoantibodies against oxidized LDL indicates the
rate of LDL oxidation in vivo. This concentration significantly decreased from
14.2 +/- 9.9 to 13.1 +/- 9.2 mg L-1 (P < 0.01). CONCLUSIONS: The beneficial
effect of gemfibrozil in reducing CHD may at least in part depend on a decrease
of the rate of LDL oxidation in vivo.
PMID- 9651558
TI - Salbutamol inhalation has no effect on myocardial ischaemia, arrhythmias and
heart-rate variability in patients with coronary artery disease plus asthma or
chronic obstructive pulmonary disease.
AB - OBJECTIVES: Inhaled beta-2 agonists raise heart rate, systolic blood pressure and
contractility, all of which cause an increase in oxygen consumption of the heart.
We performed a study on the influence of inhaled salbutamol on myocardial
ischaemia, rhythm, and heart rate variability as assessed by Holter monitoring of
24 patients with coronary artery disease (CAD) and clinically stable asthma or
chronic obstructive pulmonary disease (COPD). DESIGN: In hospital the patients
received 0.2 mg (hour 1), 0.4 mg (hour 6), 0.8 mg (hour 13) of salbutamol with a
metered-dose inhaler and a spacer, and 5 mg (hour 25) with a nebulizer; symptoms,
peak expiratory flow (PEF), 30-h Holter monitoring, and blood pressure (BP) were
recorded. The study parameters were compared for the hour preceding and following
each dose of salbutamol. RESULTS: No cardiac symptoms were associated with
salbutamol inhalation. PEF increased after all doses (P < 0.005). A dose of 0.2
mg salbutamol induced no changes in heart rate, whereas dose of 0.4 mg increased
heart rate from a mean of 75 +/- 13 to 79 +/- 14 beats min-1 (P < 0.005), and a
dose of 0.8 mg from 76 +/- 14 to 78 +/- 15 beats min-1 (P < 0.05). No changes in
systolic BP appeared after any dose of salbutamol. The diastolic BP was lowered
after 0.8 mg of salbutamol from 86 +/- 12 to 82 +/- 10 mmHg (P < 0.05). The 5 mg
of nebulized drug provoked no significant changes in heart rate or BP. Myocardial
ischaemia, heart rate variability and ventricular arrhythmias remained unaltered
with all doses. CONCLUSIONS: The commonly used doses of inhaled or nebulized
salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart
rate variability in patients with CAD and clinically stable asthma or COPD.
PMID- 9651559
TI - Efficacy and safety of systemic recombinant interferon-alpha in Behcet's disease.
AB - OBJECTIVES: To evaluate the therapeutic efficacy and safety of systemic
recombinant interferon alpha-2a (IFN-alpha) in patients with Behcet's disease
(BD) and to determine the incidence of episodes in complete responders during the
one-year pretreatment period and follow-up. DESIGN: An open clinical study.
SETTING: Departments of Dermatology and Ophthalmology, University of Patras,
Greece and Department of Dermatology, Heinrich-Heine University of Dusseldorf,
Germany. SUBJECTS: Twelve patients (aged 23-52 years) with active BD who had
previously been unsuccessfully treated with systemic steroids and/or
immunosuppressives. INTERVENTIONS: IFN-alpha was administered subcutaneously at a
dose of 6 X 10(6) IU per day 3 times per week for 2 months. MAIN OUTCOME
MEASURES: Change of area or number of mucocutaneous lesions, grading score for
thrombophlebitis and ocular inflammation, haematological and biochemical
parameters and number of episodes during the pretreatment period and the follow
up. Evaluation of IFN-alpha side effects. RESULTS: Nine patients (75.0%) revealed
a complete remission, two (16.6%) a partial remission and one patient (8.3%)
showed no response. During the follow-up in five out of the nine complete
responders (55.5%) no episodes of BD were seen, whereas, the other four patients
(44.5%) had 1-2 episodes, as compared to 5-8 and 5-12 episodes, respectively,
during the pretreatment period. An influenza-like syndrome (fever, nausea and
myalgias) appeared during the early phase of therapy in all (but one) patients.
No patient had to discontinue IFN-alpha because of intolerance. CONCLUSIONS:
Subcutaneous human recombinant interferon alpha-2a appears to be an effective and
fairly well tolerated therapy for BD.
PMID- 9651560
TI - Compliance with and efficacy of treatment with pravastatin and cholestyramine: a
randomized study on lipid-lowering in primary care.
AB - OBJECTIVES: Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A (HMG
CoA) reductase inhibitors and cholestyramine are effective in reducing
cardiovascular morbidity both in primary and secondary prevention. Patient
compliance is an important determinant of the outcome of therapy. This study was
designed to compare compliance with tolerance and lipid-lowering effectiveness of
pravastatin and/or cholestyramine in primary care. DESIGN: Nine hundred and
eighty nine women and 1047 men were randomized to treatment at 100 primary-care
centres in Sweden. After dietary intervention, an eligible patient was randomly
assigned to one of four programs of daily treatment: group Q, 16 g
cholestyramine, group QP, 8 g cholestyramine and 20 mg pravastatin, group P20, 20
mg pravastatin or group P40, 40 mg pravastatin. RESULTS: In group Q, group QP,
group P20 and group P40 the reductions in low density lipoprotein (LDL)
cholesterol were 26%, 36%, 27% and 32%. The dose actually taken was 91-95% of the
prescribed for the pravastatin treatment groups and 77-88% for the cholestyramine
groups. In the pravastatin and cholestyramine groups 76-78% and 44-53%,
respectively, completed the trial. Only 8-27% of the patients reached a serum
cholesterol target level of 5.2 mmol L-1. There was no difference in lipid
lowering effect between women and men. CONCLUSION: Pravastatin alone is
efficacious and compliance is high, independent of dose. Combined treatment with
cholestyramine and pravastatin had a better cholesterol lowering effect (although
not statistically significant) than 40 mg pravastatin. Despite this, only 8-27%
of the patients actually reached a serum cholesterol level of 5.2 mmol L-1. No
unexpected serious adverse events were detected in any of the treatment groups.
As predicted, the gastrointestinal disturbances were more common on
cholestyramine treatment. These two factors suggest that an increase in the
dosage of the HMG-CoA reductase inhibitor may be appropriate. Results from other
studies indicate that there also might be other positive effects of statin
treatment beyond cholesterol lowering.
PMID- 9651561
TI - Serum 25-hydroxyvitamin D levels and bone mineral density in 16-20 years-old
girls: lack of association.
AB - OBJECTIVE: Hypovitaminosis D has been shown to be associated with low bone
mineral density in middle-aged and elderly women. The aim of this study was to
evaluate whether such an association might exist in adolescent and young adult
girls, approaching peak bone mass. DESIGN: Cross-sectional study carried out in
late winter. SETTING: Reykjavik area at latitude 64 degrees N. SUBJECTS: Two
hundred and fifty-nine Icelandic Caucasian girls, aged 16, 18 and 20 years,
randomly selected from the registry of Reykjavik. MAIN OUTCOME MEASURES: Bone
mineral density in lumbar spine, hip, distal forearm and total skeleton was
measured with dual-energy X-ray absorptiometry (DEXA) and compared with 25
hydroxyvitamin D levels [25 (OH)D] in serum, measured by radioimmunoassay.
Calcium and vitamin-D intake were also assessed by a questionnaire. RESULTS:
18.5% of the girls were below 25 nmol L-1 in serum 25 (OH)D which has been
recognized as the lower normal limit for adults. No significant association was
found between 25 (OH)D levels and bone mineral density. CONCLUSIONS: Normal
calcium and phosphate concentrations in plasma and normal bone mineral density
are maintained in adolescent and young adult girls at lower 25 (OH)D levels than
published 'normal' levels for middle-aged and elderly.
PMID- 9651562
TI - Hypoglycaemia following pancreatic allograft transplantation.
AB - Pancreatic transplantation is an established treatment for patients with insulin
dependent diabetes mellitus. Side-effects are mainly related to surgical
complications, immunosuppressive therapy and graft rejection. We report on two
patients having recurrent hypoglycaemic events following pancreatic
transplantation. The cause of hypoglycaemia in our patients remained obscure.
Hypoglycaemia following pancreatic transplantation has been described.
Hypoglycaemic events may appear years after transplantation. In the article we
review three possible mechanisms of hypoglycaemia: hyperinsulinaemia, secondary
to systemic drainage (due to loss of first pass hepatic insulin clearance),
presence of anti-insulin antibodies and persistence of counter-regulatory
abnormalities. Physicians and patients should be aware of possible hypoglycaemia
events following transplantation.
PMID- 9651563
TI - Atherosclerosis: usage and misusage.
PMID- 9651565
TI - Cardiac tamponade preceding adrenal insufficiency--an unusual presentation of
Addison's disease.
PMID- 9651564
TI - Hyperthyroidism and pulmonary hypertension.
PMID- 9651566
TI - Neurobiology of the association of chronic work stress with atherogenic lipids
and elevated fibrinogen in middle-aged men.
PMID- 9651567
TI - Smoking cessation in patients with stable or unstable ischaemic heart disease.
PMID- 9651568
TI - The additional effects of acipimox to simvastatin in the treatment of combined
hyperlipidaemia.
AB - OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined
hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a
nicotinic acid like lipid lowering drug with less side-effects. We studied
whether the addition of acipimox to simvastatin improves the lipid profile in
patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo
controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary
referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia
treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION:
Acipimox in a daily dose of 3 X 250 mg for 12 weeks. MAIN OUTCOME MEASURES:
Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as
well as on LDL-size and LDL-resistance to oxidative modification. RESULTS:
Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not
statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All
patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size
and the resistance to oxidation, reflected in the lag phase during in vitro
oxidation, were not affected by the addition of acipimox. In a subgroup of 8
patients with the most severe hypertriglyceridaemia (baseline TG > 4 mmol L-
[1]), acipimox induced a significant increase in HDLc (+ 15%, P < 0.01). The
effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced
than in the group with a lower baseline TG, but none of these changes reached the
level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a)
and substantially but not significantly lowered TG. However, in patients with the
highest TG levels. HDLc was also significantly improved.
PMID- 9651569
TI - [Treatment costs in a medical intensive care unit: a comparison of 1992 and
1997].
AB - BACKGROUND AND OBJECTIVE: Treatment in an intensive care unit (ICU) is very
expensive. Aim of this study was to determine the exact composition of costs and
to analyse what factors are responsible for the rise in costs over the last 5
years. METHODS: In a prospective investigation all 790 patients who had been
treated at the ICU of the Medical Department of Frankfurt University during 1992
were included, findings being compared with data on all 208 patients treated in
the ICU in May and June 1997. All important diagnostic and therapeutic measures
were quantitatively determined each day. RESULTS: The mean age of the ICU
patients rose in the 5 years from 55 to 59 years (P < 0.001). Mean period of stay
in the ICU remained unchanged (4.1 days), total duration of hospital stay (15 and
12 days, respectively), and treatment intensity (sum of points according to the
"Therapeutic Intervention Scoring System" per ICU stay: 96 and 77, respectively).
The mortality rate in the ICU fell from 16.3% to 10.6% (P = 0.02), hospital
mortality rate from 23% to 14% (P = 0.01). Total cost rose from DM 797,860 to DM
1,148,945 per 100 patients (+44%). Of this total, personnel costs were DM 286,885
in 1992 and 356,091 in 1997 (+24%), costs for apparatus-based diagnostic and
therapeutic tests were DM 169,743 and 245,156, respectively (+44%), DM 98,496 and
129,222 for drugs (+31%), and DM 60,399 and 186,671 (+209%) for blood and
clotting products (in each category per 100 patients). Per case costs rose from
DM 7970 to 11,489, per day costs from DM 1943 to 2831. 90% of cost increases were
due to new strategies in the treatment of patients with myocardial infractions
and those with severe clotting disorders and a rise in personnel costs.
CONCLUSION: The costs of a stay in the ICU has greatly increased over the last 5
years, the main causes being a change to new forms of treatment, especially in
patients with myocardial infarction and those with haemophilia.
PMID- 9651570
TI - [Percutaneous balloon pericardiotomy for the treatment of a malignant pericardial
tamponade].
AB - HISTORY AND CLINICAL FINDINGS: A 72-year old man was admitted because of
increasing dyspnoea, failing fitness and weight loss. Physical examination was
unremarkable except for decreased heart sounds. INVESTIGATIONS: He was anaemic
(haemoglobin 11.7 g/dl), erythrocyte sedimentation rate was raised (80/90 mm) as
was C-reactive protein (169 mg/dl). Chest radiogram showed tent-like widening of
the cardiac silhouette and a 6 cm space-occupying lesion in the left hilus.
Echocardiography revealed pericardial effusion of up to 2.3 cm (epi- to
pericardium). TREATMENT AND COURSE: Because of an increase in dyspnoea and
pericardial effusion a pericardiocentesis was performed. This fluid and needle
biopsy of the space-occupying lesion revealed small-cell carcinoma. 6 days after
the pericardiocentesis the dyspnoea further increased as did the pericardial
effusion (to 3.9 cm). Percutaneous balloon pericardiotomy was uneventfully
performed. During a follow-up period of 14 months there were no further
pericardial effusions. CONCLUSION: Percutaneous balloon pericardiotomy can be
undertaken as a minimally invasive treatment of symptomatic pericardial effusion.
It should be considered as an alternative to surgical creation of a pericardial
window, especially in very ill patients.
PMID- 9651571
TI - [Primary pulmonary plasmacytoma. Case report of a rare lung tumor].
AB - HISTORY AND CLINICAL FINDINGS: A 45-year old man, suffering from dry cough
without haemoptysis, was admitted for evaluation of pulmonary changes of
uncertain aetiology. A chest radiograph and computed tomography (CT) had shown a
large space-occupying lesion in the left hilus. His general condition was poor
and he had resting dyspnoea and stridor. On auscultation of the lung there were
decreased breath sounds and dry rales over the left and vesicular breathing over
the right lung. INVESTIGATIONS: CT revealed a 7.0 x 6.0 cm space-occupying lesion
in the left hilus and ipsilaterally a tumour in the dorsolateral lower lobe
surrounding the left lower lobe bronchus. Initial bronchoscopy showed this
bronchus to be involved in the tumour process. Biopsy demonstrated monomorphic
proliferating plasma cells which on immunochemical testing showed selective
staining to lambda-light chains and immunoglobulin G. The first serum
electrophoresis was unremarkable, but a later repeat discovered a small amount of
paraprotein for IgG-lambda type. Bence-Jones protein was demonstrated in the
urine. On the basis of these findings an extramedullary plasmacytoma of the lung
(PPP) was diagnosed. TREATMENT AND COURSE: At first the patient was given i.v.
chemotherapy, and to prevent a threatening bronchial occlusion oral dexamethasone
was given. Pericardial effusion and recurrent retention pneumonia developed. 6
month after onset of symptoms radiotherapy was begun and the tumour became
markedly smaller. CONCLUSION: PPP should be included in the differential
diagnosis of pulmonary space-occupying lesions even when initial serum protein
electrophoresis is negative for monoclonal paraproteinaemia. Pericardial effusion
may be caused by pulmonary involvement of the plasma cell tumours.
PMID- 9651572
TI - [Angioedema caused by C1 esterase inhibitor deficiency].
PMID- 9651573
TI - [Social medicine evaluation and advice for patients with coronary heart disease].
PMID- 9651574
TI - [Anticardiolipin antibody level in myocardial infarction].
PMID- 9651576
TI - [Physical training in geriatrics].
PMID- 9651575
TI - ["Auto-continuous positive airway pressure" and "autotitration"].
PMID- 9651577
TI - The CRY1 blue light photoreceptor of Arabidopsis interacts with phytochrome A in
vitro.
AB - Plants have at least two major photosensory receptors: phytochrome (absorbing
primarily red/far-red light) and cryptochrome (absorbing blue/UV-A light);
considerable physiological and genetic evidence suggests some form of
communication or functional dependence between the receptors. Here, we
demonstrate in vitro, using purified recombinant photoreceptors, that Arabidopsis
CRY1 and CRY2 (cryptochrome) are substrates for phosphorylation by a phytochrome
A-associated kinase activity. Several mutations within the CRY1 C terminus lead
to reduced phosphorylation by phytochrome preparations in vitro. Yeast two-hybrid
interaction studies using expressed C-terminal fragments of CRY1 and phytochrome
A from Arabidopsis confirm a direct physical interaction between both
photoreceptors. In vivo labeling studies and specific mutant alleles of CRY1,
which interfere with the function of phytochrome, suggest the possible relevance
of these findings in vivo.
PMID- 9651578
TI - Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.
AB - Activation of procaspase-9 by Apaf-1 in the cytochrome c/dATP-dependent pathway
requires proteolytic cleavage to generate the mature caspase molecule. To
elucidate the mechanism of activation of procaspase-9 by Apaf-1, we designed an
in vitro Apaf-1-procaspase-9 activation system using recombinant components.
Here, we show that deletion of the Apaf-1 WD-40 repeats makes Apaf-1
constitutively active and capable of processing procaspase-9 independent of
cytochrome c an dATP. Apaf-1-mediated processing of procaspase-9 occurs at Asp
315 by an intrinsic autocatalytic activity of procaspase-9 itself. We provide
evidence that Apaf-1 can form oligomers and may facilitate procaspase-9
autoactivation by oligomerizing its precursor molecules. Once activated, caspase
9 can initiate a caspase cascade involving the downstream executioners caspase-3,
-6, and -7.
PMID- 9651579
TI - The von Hippel-Lindau tumor suppressor protein is required for proper assembly of
an extracellular fibronectin matrix.
AB - Fibronectin coimmunoprecipitated with wild-type von Hippel-Lindau protein (pVHL)
but not tumor-derived pVHL mutants. Immunofluorescence and biochemical
fractionation experiments showed that fibronectin colocalized with a fraction of
pVHL associated with the endoplasmic reticulum, and cold competition experiments
suggested that complexes between fibronectin and pVHL exist in intact cells.
Assembly of an extracellular fibronectin matrix by VHL-/- renal carcinoma cells,
as determined by immunofluorescence and ELISA assays, was grossly defective
compared with VHL+/+ renal carcinoma cells. Reintroduction of wildtype, but not
mutant, pVHL into VHL-/- renal carcinoma cells partially corrected this defect.
Finally, extracellular fibronectin matrix assembly by VHL-/- mouse embryos and
mouse embryo fibroblasts (MEFs), unlike their VHL+/+ counterparts, was grossly
impaired. These data support a direct role of pVHL in fibronectin matrix
assembly.
PMID- 9651580
TI - The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double
strand breaks.
AB - MRE11 and RAD50 are known to be required for nonhomologous joining of DNA ends in
vivo. We have investigated the enzymatic activities of the purified proteins and
found that Mre11 by itself has 3' to 5' exonuclease activity that is increased
when Mre11 is in a complex with Rad50. Mre11 also exhibits endonuclease activity,
as shown by the asymmetric opening of DNA hairpin loops. In conjunction with a
DNA ligase, Mre11 promotes the joining of noncomplementary ends in vitro by
utilizing short homologies near the ends of the DNA fragments. Sequence
identities of 1-5 base pairs are present at all of these junctions, and their
diversity is consistent with the products of nonhomologous end-joining observed
in vivo.
PMID- 9651581
TI - A mouse model for the basal transcription/DNA repair syndrome
trichothiodystrophy.
AB - The sun-sensitive form of the severe neurodevelopmental, brittle hair disorder
trichothiodystrophy (TTD) is caused by point mutations in the essential XPB and
XPD helicase subunits of the dual functional DNA repair/basal transcription
factor TFIIH. The phenotype is hypothesized to be in part derived from a
nucleotide excision repair defect and in part from a subtle basal transcription
deficiency accounting for the nonrepair TTD features. Using a novel gene
targeting strategy, we have mimicked the causative XPD point mutation of a TTD
patient in the mouse. TTD mice reflect to a remarkable extent the human disorder,
including brittle hair, developmental abnormalities, reduced life span, UV
sensitivity, and skin abnormalities. The cutaneous symptoms are associated with
reduced transcription of a skin-specific gene strongly supporting the concept of
TTD as a human disease due to inborn defects in basal transcription and DNA
repair.
PMID- 9651582
TI - Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF
and inhibits 3'end formation of cellular pre-mRNAs.
AB - Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the
influenza A virus NS1 protein requires its effector domain. Here, we demonstrate
that the NS1 effector domain functionally interacts with the cellular 30 kDa
subunit of CPSF, an essential component of the 3' end processing machinery of
cellular pre-mRNAs. In influenza virus-infected cells, the NS1 protein is
physically associated with CPSF 30 kDa. Binding of the NS1 protein to the 30 kDa
protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end
cleavage and polyadenylation of host pre-mRNAs. The NS1 protein also inhibits 3'
end processing in vivo, and the uncleaved pre-mRNA remains in the nucleus. Via
this novel regulation of pre-mRNA 3' end processing, the NS1 protein selectively
inhibits the nuclear export of cellular, and not viral, mRNAs.
PMID- 9651583
TI - Coordinated leading and lagging strand DNA synthesis on a minicircular template.
AB - The coordinated synthesis of both leading and lagging DNA strands is thought to
involve a dimeric DNA polymerase and a looping of the lagging strand so that both
strands can be synthesized in the same direction. We have constructed a
minicircle with a replication fork that permits an assessment of the
stoichiometry of the proteins and a measurement of the synthesis of each strand.
The replisome consisting of bacteriophage T7 DNA polymerase, helicase, primase,
and single-stranded DNA-binding protein mediates coordinated replication. The
criteria for coordination are fulfilled: (1) a replication loop is formed, (2)
leading and lagging strand synthesis are coupled, (3) the lagging strand
polymerase recycles from one Okazaki fragment to another, and (4) the length of
Okazaki fragments is regulated. T7 single-stranded DNA-binding protein is
essential for coordination.
PMID- 9651584
TI - Assembly of a 12/23 paired signal complex: a critical control point in V(D)J
recombination.
AB - The 12/23 rule requires that V(D)J recombination only occurs between
recombination signals with 12 and 23 base pair spacers. We show that the 12/23
rule is established prior to DNA cleavage, by the formation of a synaptic complex
containing both 12-spacer and 23-spacer signals. The RAG1 and RAG2 proteins, as
well as the DNA bending protein HMG1, are needed for efficient formation of this
complex. We show further that the synaptic complex is the functional complex for
coupled cleavage. After cleavage, all four broken DNA ends remain associated with
the RAG proteins in a postcleavage synaptic complex, whose existence helps to
explain the known role of RAG1 and RAG2 in the subsequent end-joining events that
complete V(D)J recombination.
PMID- 9651585
TI - SAP30, a novel protein conserved between human and yeast, is a component of a
histone deacetylase complex.
AB - Histone acetylation plays a key role in the regulation of eukaryotic gene
expression. Recently, histone acetylation and deacetylation were found to be
catalyzed by structurally distinct, multisubunit complexes that mediate,
respectively, activation and repression of transcription. Here, we identify SAP30
as a novel component of the human histone deacetylase complex that includes Sin3,
the histone deacetylases HDAC1 and HDAC2, histone binding proteins RbAp46 and
RbAp48, as well as other polypeptides. Moreover, we describe a SAP30 homolog in
yeast that is functionally related to Sin3 and the histone deacetylase Rpd3. The
human SAP30 complex is active in deacetylating core histone octamers, but
inactive in deacetylating nucleosomal histones due to the inability of the
histone binding proteins RbAp46 and RbAp48 to gain access to nucleosomal
histones. These results define SAP30 as a component of a histone deacetylase
complex conserved among eukaryotic organisms.
PMID- 9651586
TI - Transcriptional pausing at +62 of the HIV-1 nascent RNA modulates formation of
the TAR RNA structure.
AB - A strong transcriptional pause delays human RNA polymerase II three nt after the
last potentially paired base in HIV-1 TAR, the RNA structure that binds the
transactivator protein Tat. We report here that the HIV-1 pause depends in part
on an alternative RNA structure (the HIV-1 pause hairpin) that competes with
formation of TAR. By probing the nascent RNA structure in halted transcription
complexes, we found that the transcript folds as the pause hairpin before and at
the pause, and rearranges to TAR concurrent with or just after escape from the
pause. The pause signal triggers a 2 nt reverse translocation by RNA polymerase
that may block the active site and be counteracted by formation of TAR. Thus, the
HIV-1 pause site modulates nascent RNA rearrangement from a structure that favors
pausing to one that both recruits Tat and promotes escape from the pause.
PMID- 9651587
TI - Conditional loss-of-myosin-II-function mutants reveal a position in the tail that
is critical for filament nucleation.
AB - Myosin-II must be assembled into filaments to perform its cellular functions. Two
conditional loss-of-myosin-II-function mutants were recovered from a previous
genetic screen with defects that were mapped to the coiled-coil tail region of
Dictyostelium myosin-II. Strikingly, both tail mutations affected the same
arginine residue at position 1880. A single amino acid substitution, R1880P,
disrupted both the dimerization and tetramerization steps of filament nucleation.
Even a single charge reversal at this position, R1880D, was sufficient to inhibit
filament assembly, while other single charge reversals in the region of
antiparallel contract suppressed these filament assembly mutants. The
considerable impact of small electrostatic forces on nucleation suggests that
these steps are delicately balanced and easily reversible.
PMID- 9651588
TI - A single amino acid change in the yeast retrotransposon Ty5 abolishes targeting
to silent chromatin.
AB - Many retrotransposons and retroviruses are thought to select integration sites
through interactions with specific chromosomal proteins. In yeast, the Ty5
retrotransposon integrates preferentially with regions bound by silent chromatin,
namely the telomeres and the HMR and HML mating loci. A Ty5 mutant (M3) was
identified with an approximately 20-fold decrease in targeted integration as
measured by a plasmid-based targeting assay. Often chromosomal insertions
generated by M3, none were located at the telomeres or silent mating loci. A
single amino acid change at the boundary of integrase and reverse transcriptase
is responsible for the mutant phenotype. We predict that this mutation lies
within a targeting domain that mediates Ty5 target choice by interacting with a
component of silent chromatin.
PMID- 9651589
TI - The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein
with homology to the transcription factor YY1.
AB - Genes of the Polycomb group (PcG) of Drosophila encode proteins necessary for the
maintenance of transcriptional repression of homeotic genes. PcG proteins are
thought to act by binding as multiprotein complexes to DNA through Polycomb group
response elements (PREs); however, specific DNA binding has not been demonstrated
for any of the PcG proteins. We have identified a sequence-specific DNA binding
protein that interacts with a PRE from the Drosophila engrailed gene. This
protein (PHO) is a homolog of the ubiquitous mammalian transcription factor Yin
Yang-1 and is encoded by pleiohomeotic, a known member of the PcG. We propose
that PHO acts to anchor PcG protein complexes to DNA.
PMID- 9651590
TI - A conserved sequence motif in Polycomb-response elements.
PMID- 9651591
TI - Intravascular imaging.
AB - Based on three-dimensional (3D) information, quantitative data such as plaque
volume can be calculated. The procedure includes automatic contour detection
based in image segmentation methods and greatly speeds up clinical evaluation.
With the use of additional X-ray information, the true tortuous vessel geometry
can be reconstructed in 3D. This allows, by numerical modelling techniques, to
calculate endothelial shear stress values which in turn may indicate sites prone
to stenosis. With a decorrelation technique for radio frequency (RF) echo
information from sequential data in the same beam direction and integration
method over the entire cross section, blood velocity can be shown colour-coded
during the cardiac cycle, while even blood flow quantification seems to be
possible. In vitro as well as animal experiments have shown the feasibility of
the method. Intravascular imaging can be used to study the biomechanical
properties of atheroma components. Local radial strain as a measure of local
tissue hardness can be estimated in principle. Hard or soft plaques can be
identified from the strain images independently of the echogenic contrast between
plaque and vessel wall.
PMID- 9651592
TI - Three-dimensional ultrasound imaging of the vasculature.
AB - With conventional ultrasonography, the diagnostician must view a series of two
dimensional images in order to form a mental impression of the three-dimensional
anatomy, an efficient and time consuming practice prone to operator variability,
which may cause variable or even incorrect diagnoses. Also, a conventional two
dimensional ultrasound image represents a thin slice of the patients anatomy at a
single location and orientation, which is difficult to reproduce at a later time.
These factors make conventional ultrasonography non-optimal for prospective or
follow-up studies. Our efforts have focused on overcoming these deficiencies by
developing three-dimensional ultrasound imaging techniques that are capable of
acquiring B-mode, colour Doppler and power Doppler images of the vasculature, by
using a conventional ultrasound system to acquire a series of two-dimensional
images and then mathematically reconstructing them into a single three
dimensional image, which may then be viewed interactively on an inexpensive
desktop computer. We report here on two approaches: (1) free-hand scanning, in
which a magnetic positioning device is attached to the ultrasound transducer to
record the position and orientation of each two-dimensional image needed for the
three-dimensional image reconstruction; and (2) mechanical scanning, in which a
motor-driven assembly is used to translate the transducer linearly across the
neck, yielding a set of uniformly-spaced parallel two-dimensional images.
PMID- 9651593
TI - Edge detection in prostatic ultrasound images using integrated edge maps.
AB - OBJECTIVE: We investigated an algorithm to detect grey level transitions with
multiple scales of resolution to improve edge detection and localisation in
ultrasound images of the prostate. INTRODUCTION: We had developed a non
analytical operator for prostate contour determination implemented with minimum
and maximum filters and locate edges. We implemented a technique for improved
determination of boundary parts in prostatic ultrasound images by adjusting the
edge detection parameter to signal information. METHODS: First the influence of
prefilter settings and edge detection parameters is investigated in a test image
and a real ultrasound image. Then, local standard deviation is used to identify
or fewer homogeneous regions that are filtered with course resolution, while
areas with larger deviation that grey level transitions occur, which should be
preserved using smaller filter sizes to improve edge localisation. RESULTS:
Analysis of images with different filter sizes indicated that areas are merged
for increasing filter sizes: less pronounced edges disappear or displace for
larger filters. Two scales of resolution lead to an improved localisation of
edges when smaller filter sizes are used in areas with an increased local
standard deviation. CONCLUSIONS: This paper illustrates an edge detection method
suitable as pre-processing step in interpretation of medical images. By adapting
input parameters to signal information, object recognition can be applied in
images from different imaging modalities. Also, disadvantages are discussed,
resulting in a new application combining a localisation algorithm to find the
initial contour and a delineation algorithm to improve the outlining of the
resulting contour.
PMID- 9651594
TI - Real-time sonomammography based on the intersecting canonical body approximation
of the diffracted wave field.
AB - The inverse problem of the identification of an anomalous object (e.g., cyst or
tumor) in a female breast immersed in water is solved by the matching of
theoretical fields (for trial objects), employing an approximate field ansatz, to
the scattered ultrasonic wave field measured on a surface fully enclosing the
object.
PMID- 9651596
TI - Quality assurance tools for therapeutic ultrasound.
AB - Compared to diagnostic ultrasound, special phantoms and measurement techniques
for therapeutic ultrasound are still far from standardization. In the following
article, the development of quality assurance (QA) tools for two therapy methods
are described: Extracorporeal shockwave lithotripsy (ESWL) and high intensity
focused ultrasound (HiFU). The three consequent parts are QA tools in research
and development, QA in clinical environment and standardization. For part one the
computerized scanning with hydrophones, the use of Schlieren optics and sound
force balances are state of the art. For clinical use the test procedures have to
be simple so that routine checking of the equipment becomes convenient.
PMID- 9651595
TI - Development of an example flow test object and comparison of five of these test
objects, constructed in various laboratories.
AB - Doppler test objects are used to characterise Doppler systems, both stand-alone
systems and the Doppler part of so-called duplex scanners. The aim of the project
partially presented here is the development and validation of an example of a
Doppler test object fulfilling the requirements of the IEC 1685. The project has
been carried out by nine partners of five European countries and has been funded
by the European Commission. The flow Doppler test object is composed of: tissue
mimicking material (TMM), blood mimicking fluid (BMF), tube (embedded in the TMM
and carrying the BMF), tank flow system, including a pump and a flow meter. In
the normative part of the IEC 1685, requirements are given for the values of
acoustical parameters of TMM and BMF such as sound velocity, attenuation and
backscattering. For BMF, requirements are given also for values of density and
viscosity. In an informative (but not compulsory) annex, a description is given
of a flow test object meeting these requirements as an example. 'example test
object' developed during the project is composed of TMM based on agar and
including SiC- and Al2O3-powders, BMF based on nylon particles suspended in water
and glycerine, and a tube of c-flex, a silicon copolymer. Two tube sizes are
used: 4.0 mm ID and 8.0 mm ID. During the project, very precise recipes have been
developed for the composition and preparation of both TMM and BMF. Based on these
recipes and a description of the construction in a design five flow test objects
have been constructed in the laboratories of five participants. The test objects
have been compared by measurements of the physical parameters and by Doppler
measurements of the five test objects with the Doppler system. The measurements
have been carried out by five observers. Inter-test object and inter-observer
variabilities are determined, yielding information about usefulness of the
parameters.
PMID- 9651597
TI - Design and in vitro results of a high intensity ultrasound interstitial
applicator.
AB - Interstitial technologies were proposed for the treatment of deep-seated and
unresectable tumours. This study was designed to demonstrate the possibility of
producing coagulation necrosis for a short exposure duration (20s) and a large
volume with an interstitial ultrasonic applicator equipped with a plane
transducer. The applicator was evaluated in terms of electroacoustic efficiency
(58% at 10.7 MHz), temperature pattern and in vitro pig liver tissues
destruction. The temperature elevation reached 52, 39, 22 and 15 degrees C at,
respectively, 2.5, 7.5 and 10 mm from the applicator surface along the
propagation axis. The evident cigar-shaped lesions spread on a depth of (8 +/- 2)
mm from the surface applicator, (10 +/- 1) mm high and (3 +/- 1) mm high and (3
+/- 1) mm wide. The temperature measurements showed the limitations encountered
with a 10 MHz transducer. The high increase in temperature of tissues close to
the transducer can induce vaporisation and a gaseous barrier opaque to
ultrasound. Owing to the shape and the operating frequency of the transducer, we
hope to obtain the same satisfactory performances in vivo with weakly perfusion
dependent lesions. Axial and longitudinal applicator motions will enable us to
treat more important volumes.
PMID- 9651598
TI - The generation of negative pressure waves for cavitation studies.
AB - A technique for producing strong focused negative pressure waves in water is
described. The method is based on the phase inversion of the planar shock wave
from an electromagnetic transducer. This is achieved by reflection and focusing
at a pressure release boundary. The acoustic concentrator has a phase inverting
central element and a phase maintaining annular mirror. Focal pressures of
approximately -16 MPa from an initial +5 MPa EMAT source have been measured and
the focal volume was found to be approximately the same as that obtained with a
conventional ultrasonic lens. The electromagnetic transducer and the parabolic
concentrator is an excellent source of cavitation bubbles in water. The focused
negative wave has been observed using high speed laser-lit Schlieren photography.
PMID- 9651600
TI - On the effect of lung filtering and cardiac pressure on the standard properties
of ultrasound contrast agent.
AB - The goal standard of contrast echocardiography is the absolute measure of
myocardial perfusion using a contrast agent. Actually, several contrast agents
are developed. All these agents show left ventricular opacification after
intravenous injection. However, none of these agents shows an acceptable
enhancement of the myocardium yet using conventional imaging techniques. The
explanation of this phenomenon should be easy by measuring the acoustic
characteristics of the contrast agent and then making a comparison of these
characteristics with those of the myocardium. In this study we present
definitions of standard acoustic parameters of ultrasound contrast agent, the
backscatter coefficient Bs and the scattering-to-attenuation ratio STAR.
Afterwards, considering an intravenous injection of the contrast agent, and
taking into account the effects of lung filtering and cardiac pressure, the
standard properties of contrast agents are determined in different sites: right
ventricle (before lung passage), left ventricle (after lung passage and taking
into account the pressure effect) and in the coronary system. Calculations showed
that the acoustic properties are considerably influenced by these two effects:
lung filtering and cardiac pressure. Comparison of these properties with the
tissue properties (myocardium) is then performed. This determines the
contribution of the contrast agent to the enhancement of the tissue
visualization. The simulations are performed on Albunex microspheres. The results
reveal that the difference between scattering of the myocardium and scattering of
intravenously injected Albunex is too slight to be visible on an echographic
image.
PMID- 9651599
TI - Clinical applications of ultrasound contrast agents.
AB - Within the last decade safe and practical ultrasound contrast agents have been
introduced. Most of these are based on gas-filled microbubbles, which markedly
enhance Doppler signals and, in some cases, also gray-scale images. The clinical
improvements expected from ultrasound contrast is reviewed. Tissue-specific
contrast agents constitute another area of potential clinical significance. One
particular agent is taken up by the reticulo-endothelial system and produces so
called acoustic emission signals when imaged. An introduction to the unique
clinical applications of acoustic emission is given. Harmonic imaging is a new
contrast-specific imaging modality, which utilizes the nonlinear properties of
some agents in an attempt to alleviate current limitations of ultrasound contrast
studies. Examples of harmonic images are presented.
PMID- 9651601
TI - Effect of ultrasound on the release of micro-encapsulated drugs.
AB - Although ultrasound is used extensively in medical therapies and diagnostics, it
has been recognized only recently as a method for external controlled diversity
of drugs. In this paper, firstly, a literature review on drug delivery and the
combination with ultrasound is given. Then an experiment is described on
measuring the release of a model drug (hexabrix) under ultrasound irradiation,
from a polymer carrier.
PMID- 9651603
TI - [Predictive factors for development of hemolytic uremic syndrome (HUS) and early
intensive treatments for prevention of HUS enterohemorrhagic Escherichia coli
infection].
AB - Predictive factors for the development of hemolytic uremic syndrome (HUS) were
evaluated in 88 inpatients who suffered from enterohemorrhagic E. coli infections
in the outbreak in Sakai, 1996. All in- and outpatients received oral or
intravenous fosfomycin within acute phase of hemorrhagic colitis, and HUS
complicated 1.4% of them. Persistence of bloody stools and diarrhea were longer
in HUS patients than in non-HUS patients, but persistence of abdominal pain was
not different in either group. Leukocytosis with leukocyte counts over
15,000/microliters and/or elevated CRP level over 2.0 mg/dl at admission, and
fever and/or vomiting in the course of hemorrhagic colitis were more frequent in
HUS patients than in non-HUS patients. Early intensive treatments including
gammaglobulin, urinastatin, aspirin, and dipyridamole were employed in 34 high
risk patients for prevention of HUS. These patients were estimated to be at risk
of developing HUS because of incomplete HUS, nephropathy, elevated LDH level,
thrombocytopenia, or age younger than two years old. These treatments were
clinically effective.
PMID- 9651602
TI - Characterising ultrasonic physiotherapy systems by performance and safety now
internationally agreed.
AB - The IEC 1689 standard specifies: methods of measurement, characterisation of the
output performance, requirements for safety due to the ultrasonic field
generated, characteristics to be declared by manufacturers and acceptance
criteria for aspects of performance. For the characterisation, reference as well
as routine testing methods are described. Important parameters such as effective
radiating area (AER), beam nonuniformity ratio (RBN) (characterising 'hot-spots':
potentially harmful to patients) and beam type have been re-defined. The quality,
reproducibility and accuracy of measurements of AER are significantly improved
compared to those in IEC 150 (which is now replaced) and the FDA 1050.10 (USA)
standards. As a result, values of effective intensity are shown to be
significantly higher than those obtained using the FDA 1050.10 (USA) definitions.
As it may be expected that the new standard will be implemented worldwide, this
problem is just a matter of time. The standard discussed above specifies the need
for acoustic power measurement with an accuracy of more than 15%. However,
several investigations carried out over the last ten years show a lack of proper
facilities to calibrate the acoustic output power at physiotherapy levels. A
project to investigate the complications and to produce definitive guidance for
therapy-level power measurements is funded by the EC and has been started
recently. Future activities will be undertaken to estimate the expected
temperature rise in tissue due to the ultrasonic field. Such a figure may result
in an improved judgement of the ultrasonic safety aspects of physiotherapy
systems.
PMID- 9651604
TI - [Efficacy and safety of sulbactam/cefoperazone for hepato-biliary infections].
AB - We studied efficacy and safety of sulbactam/cefoperazone (SBT/CPT) in the
treatment of biliary tract infections in hospitalized patients at 26 hospitals
from February 1993 to March 1995. Secondary to dropout, 273 out of 338 patients
entered in the study were evaluated, 127 patients with cholecystitis, 132
patients with cholangitis, and 14 patients with liver abscesses. Of these, 93
patients (34.1% had malignancy as an underlying disease. SBT/CPZ had an efficacy
of 79.9% (218 patients; excellent: 52, good: 166), with the efficacy in patients
with cholecystitis, cholangitis and liver abscess at 89.0% (113 patients), 77.3%
(102 patients and 21.4% (3 patients), respectively. A significant difference (p <
0.05) was observed in the efficacy rates of patients with (59 patients [63.4%])
and without malignancy (159 patients [88.3%]). A total of 84 strains were
isolated from bile specimens of 53 patients, and the major isolates were
Escherichia coli, Pseudomonas aeruginosa and Enterococcus spp. Two or more
bacterial strains were isolated simultaneously in 20 patients. Mild or moderate
side effect (allergic reaction including rash etc.) were noted in 4 patients
(1.18%), and laboratory abnormalities (increased GOT, etc.) were in 16 patients
(4.71%) out of the total 338 patients. This study clearly demonstrated that
SBT/CPZ retains its excellent clinical efficacy and safety profile, throughout
its use over the past decade.
PMID- 9651605
TI - Concentration of levofloxacin in cervical mucus and its clinical effects on
cervicitis.
AB - An investigation was made on the concentration of levofloxacin (LVFX) in cervical
mucus and its clinical effects on cervicitis. The results were as follows: 1) The
concentrations of orally administered LVFX in the cervical mucus of 110 subjects
were determined by HPLC. During 1-4 hour after the administration the mean
concentration of LVFX in the cervical mucus reached a level of 2 micrograms/g,
which was higher than the serum level. The transfer of LVFX to the cervical mucus
was almost the same as that to other genital organs. 2) When LVFX was given to
102 patients at a dose of 100-200 mg, t.i.d for 4-5 days and the efficacy was
evaluated with clinical improvement, the clinical efficacy rate of LVFX was
72/102 (70.6%). Significant bacteriological effects were observed in 70/73
(95.9%), especially, the disappearance rate of C. trachomatis was 18/18 (100%).
3) The administration LVFX did not cause any subjective or objective side effects
and any abnormalities were not detected in the laboratory test done in this
study. These results demonstrate that LVFX can be sufficiently transferred to the
cervical mucus for the treatment of cervicitis due to the infection of C.
trachomatis etc.
PMID- 9651606
TI - [Antimicrobial activities of clindamycin against clinical isolated Streptococcus
pneumoniae].
AB - We investigated antimicrobial activity of clindamycin (CLDM) against clinically
isolated Streptococcus pneumoniae in 1996. The results are summarized as follows;
1. The detection frequencies of macrolides (MLs)-resistance against penicillin
(PC)-susceptible S. pneumoniae (PSSP) was 48.0% and those against PC-intermediate
S. pneumoniae (PISP)/ PC-resistant S. pneumoniae (PRSP) was 92.0%. 2. It was
found that the ratio of MLs-inducible resistant strains of PSSP was 24.6% and
that of PISP/PRSP was 66.0%. MLs-constitutive resistant strains of PSSP accounted
for 24.0% and that of PISP/PRSP for 26.0%. MLs-constitutive resistant strains was
relatively frequent in PSSP and MLs-inducible resistant strains was frequent in
PISP/PRSP. 3. CLDM showed strong antimicrobial activity against MLs-inducible
resistant strains. The MIC70 of CLDM against PSSP was < or = 0.025 microgram/ml
and that against PISP/PRSP was 0.1 microgram/ml. From these results, it was
suggested that CLDM is effective against the infection of PISP/PRSP where the
detection frequency of MLs-inducible strains was high. 4. Antimicrobial activity
of CLDM was found to be strong against MLs-inducible resistant strains, but to be
weak against MLs-constitutive resistant strains. When S. pneumoniae is detected,
susceptibility of the strain to CLDM should be examined.
PMID- 9651607
TI - [Studies on penetration of cefepime into respiratory tract using broncho-alveolar
lavage and sputum].
AB - We investigated broncho-alveolar distribution of cefepime (CFPM), a fourth
generation cephem, using 38 BALF specimens from 19 serious pneumonia patients who
underwent artificial respiratory system control. The mean broncho-alveolar CFPM
level was 3.44 microgram/ml (5.34% of the mean peak blood level). We thus
observed that the BALF level after a single dose of 1 g of CFPM exceeds the MIC90
of the drug against RTI causing bacteria such as Streptococcus pneumoniae,
Klebsiella pneumoniae, Haemophillus influenzae, Branhamella catarrhalis,
coagulase-negative Staphylococcus, Pseudomonas aeruginosa and Staphylococcus
aureus.
PMID- 9651608
TI - Cochlear implantation: past and present.
AB - Experimental stimulation of the ear started at the end of the 18th century with
Volta. The first electrode implantation was performed by Djouno and Eyries in
1957. This was followed by intensive cochlear implant research at first in
California, then all over the world. During the past 2 decades there has been an
evolution from single to high performance multichannel implants with the
development of more sophisticated speech coding strategies.
PMID- 9651609
TI - Cochlear implantation: an overview of existing implants.
AB - Cochlear implants (CI) bypass the external and middle ear and parts of the inner
ear, by delivering electrical stimuli to the remaining neural fibres of the
acoustic nerve in a meaningful way. Many features of current CI are similar. They
are all multi-channel devices with intracochlear placement of the active
electrodes and with transcutaneous information and energy transfer. Factors
affecting the auditory performance of CI recipients are patient-linked factors
and device factors. An overview is given of key design parameters, processing
characteristics and specifications of following CI platforms: Clarion S-Series,
Combi 40 and Combi 40+, Digisonic DX 10, Laura-Flex and nucleus CI22 and CI24M.
These data, combined with outcome parameters can enhance the information of CI
teams, patients or parents of children in their decision making process when
faced with a hearing impairment to such an extent that hearing aids are of little
or no benefit.
PMID- 9651610
TI - The LAURA Pediatric Cochlear Implant Program in Antwerp: what have we learnt in 5
years?
AB - The LAURA Cochlear Implant Program at the University of Antwerp was initiated 5
years ago. Up to now 50 children have received the LAURA cochlear implant
(Philips Hearing Implants). Our accumulated experience in selecting the patients,
counselling their parents, implanting and fitting the device allowed us to
gradually modify the inclusion/exclusion criteria for cochlear implantation and
achieve very rewarding results. The most important change was the gradual shift
towards a younger age at implantation, our youngest implantee being 11 months
old. In this paper we describe the rationale for this change, as well as the
prerequisites for a successful pediatric cochlear implant program.
PMID- 9651611
TI - Congenitally deaf children following cochlear implantation.
AB - The aim of this study is to determine the auditory performance of congenitally
deaf children following cochlear implantation. A prospective study is undertaken
of 71 such children who have been implanted in a dedicated paediatric cochlear
implant centre and who have been followed up to 3 years following implantation.
All children are aged less than 8 years at the time of implantation and all
receive a multichannel cochlear implant system. No child meeting these criteria
has been excluded from the study. The average age at implantation is 56.5 months
(range 27 to 93 months, standard deviation 15.9 months). Auditory performance is
assessed by using the Categories of Auditory Perception (CAP) scale which is
developed primarily as a clinical tool for evaluating profoundly deaf young
children following cochlear implantation. The median score prior to implantation
on this scale is Category 0 (no awareness of environmental sound), at the 1 year
interval is Category 4 (discrimination some speech sounds without lip-reading),
and at the 2 and 3 year interval, the median score on the CAP scale is Category 5
(understanding of common phrases without lip-reading). These results indicate the
ability of cochlear implants to provide significant auditory receptive skills to
young congenitally deaf children.
PMID- 9651612
TI - New developments in cochlear implants.
AB - Essential to improve the performance with cochlear implants is a better control
of the electrode-nerve interface. The long-term stability of the electrode
characteristics has to be guaranteed. Most important herein is to have a low and
stable electrical impedance and to prevent fibrosis. Results of electrode coating
and fibrosis-inhibiting products are described. To assess the properties of the
electrode-nerve interface such as stimulation threshold, spatial selectivity and
channel interaction, the electrically evoked compound action potential is
measured. The measurement paradigm and the first results are described. Models of
auditory nerve response to electrical stimulation can be used as a tool for
cochlear implant fitting. A simple model is proposed and its predictions are
compared with measured responses.
PMID- 9651613
TI - Developments in speech processing for cochlear implants.
AB - The status of speech processing for cochlear implants is reviewed. Points of
interest to enhance further speech intelligibility based on improved signal
processing, are discussed.
PMID- 9651614
TI - Imaging and cochlear implant.
AB - The auditory pathway imaging may be morphologic and/or functional. The high
resolution computed tomography and the magnetic resonance imaging (MRI) provide
an evaluation of the anatomical and structural landmarks useful for a safe and
successful cochlear implantation. The electrical stimulations supplied by the
cochlear implant give rise to ascending electrochemical activities reaching the
cortex. These activities can be recorded with scalp electrodes by Evoked
Potentials (EP) or fields techniques and eventually translated in isochronic or
isopotential brain mapping. These techniques provide a very sharp temporal
resolution with an imprecise spatial resolution. The late auditory EP of
implantees are closely comparable to the responses of normal hearing people. The
neuronal metabolism's increase is associated with a cerebral blood flow increase.
Comparing regional cerebral blood flow (rCBF) between two or more conditions
allows the localisation of brain areas involved in a fixed task. Single photon or
positron emission tomography and functional MRI (fMRI) demonstrate cBF changes
associated with an auditory stimulation. (f)MRI is contraindicated in cochlear
implantees.
PMID- 9651615
TI - Some reflections on distribution of centres for cochlear implants.
AB - Belgian has about 10 million inhabitants. Flanders has five and a half million
inhabitants and five "CI-implant centre". As the ENT-community is not able to
find sensible solutions to regulate this absurdity of one CI-centre per one
million inhabitants (in Antwerp even one per 150,000 inhabitants) some legal
activity should be provided by the government.
PMID- 9651616
TI - The additional hospital costs and outcome of the LAURA Cochlear Implant in the
Department of Otorhinolaryngology, Head and Neck Surgery of the University
Hospitals, Leuven.
AB - The additional hospital costs and the effects of cochlear implantation are
described. From the start in 1994 until 1996 ten patients, 8 adults and 2
children, received a cochlear implant after careful preoperative selection. Only
the 8 deaf adults implanted with the LAURA cochlear implant in the department of
Otorhinolaryngology, Head and Neck Surgery of the University Hospital Leuven will
be included in this retrospective analysis. In this study, the additional
hospital costs associated with cochlear implantations are estimated. In
estimating the costs, a differentation is made between 'fixed' costs and
'variable' costs. In general the costs of cochlear implantation is high: an
average cost of 1,186,741, -Bef per implanted adult and a direct fixed cost of
262,880, -Bef for the computer requisites. To evaluate the effect of cochlear
implantation a standard test, the AN-test battery, is used. In general, the
cochlear implant enhances the speech perception scores in the postlingually
deafened as well as in the prelingually deafened adults. After intensive
training, all implanted adults of the University hospital Leuven could recognize
the segmental aspects of speech with scores above the level of significance. The
cochlear implant has also a positive psychological and social impact.
PMID- 9651617
TI - A tentative exploration of the character of pediatric cochlear implant critique.
AB - Deaf communities have resisted pediatric cochlear implants in many western
countries since the introduction of the technique in the late 1970's. In this
struggle they have been supported by quite a few scientists from a diverse,
albeit social scientific background. The arguments of the latter have been the
source of much misapprehension. In this paper we will explore this
misapprehension by structurally probing for implicit conceptualisations of
benefit and legitimation procedures in the discourse of proponents and opponents
alike.
PMID- 9651618
TI - OSHA's renewed mandate for regulatory flexibility review: in support of the 1984
ethylene oxide standard.
AB - BACKGROUND: The Regulatory Flexibility Act of 1980 requires that all federal
agencies consider the impact of regulations on small entities. One of the
provisions of the Act requires review of regulations ever 10 years to determine
whether such regulations should be continued without changes, rescinded, or
amended to make them more effective or less burdensome on businesses. The Small
Business Regulatory Enforcement Fairness Act (SBREFA) of 1996 amended and
expanded the Regulatory Flexibility Act. Most significantly, SBREFA entitles
aggrieved small entities or their representative (e.g., trade associations) to
sue OSHA for failure to fulfill Regulatory Flexibility Act requirements. In
response to this new political reality, OSHA held the first public meeting of
their kind in June of 1997 to gather information on the ethylene oxide and lock
out/tag-out standards for the purposes of Regulatory Flexibility review. METHOD:
This paper presents the development of the Regulatory Flexibility review process
and details our analysis of the ethylene oxide standard using OSHA's eight
Regulatory Flexibility review criteria. RESULTS: Great progress in ethylene oxide
health and safety has been made since the promulgation of the standard in 1984,
including a considerable decrease in average workshift exposures. Yet, important
concerns remain, such as the lack of safer substitutes for EtO's most common
uses, the widespread occurrence of accidental exposures to EtO that are not
captured by personal monitoring, and the recent increase in the occurrence of
catastrophic EtO explosions. CONCLUSIONS: Because of the considerable study that
has been devoted to EtO and to the EtO standard, there is a very strong cases for
either making the EtO standard more worker protective, or continuing the standard
without change while improving outreach and enforcement efforts to address
shortcomings. Other valuable standards for which fewer data exist may be
inappropriately threatened by the Regulatory Flexibility review process.
Importantly, Regulatory Flexibility review could be constructive if accompanied
by appropriations to fund sound evaluation studies. Instead, it will likely
divert OSHA's limited resources from the numerous urgent health hazard that await
initial rule-making. As signified by the designation of "intervention
effectiveness research" as one of the 21 priorities on the National Occupational
Research Agenda, evaluation studies of OSHA standards and other interventions are
urgently needed. The occupational health community's response to this need will
play a crucial role in preserving hard-won protections, as well as in developing
other urgently needed protections in the future.
PMID- 9651619
TI - Construction injury rates may exceed national estimates: evidence from the
construction of Denver International Airport.
AB - BACKGROUND: Construction of Denver International Airport (DIA) provided a unique
opportunity to describe the magnitude of injury on a major construction project
for which complete data on injury and hours at risk were available for over
32,000 employees working 31 million hours. METHODS: Comprehensive payroll data
for all workers, who were paid standard Davis-Bacon wages, allowed calculation of
person-hours at risk by job classification. Complete reporting, facilitated by a
single workers' compensation plan covering all contracts and by an on-site
medical clinic and designated provider system, allowed us to determine both total
and lost-work-time (LWT) injury rate per 200,000 hours at risk by industrial
sector, company size, and year of construction. Workers' compensation payment
rates were calculated and compared with expected loss rates, derived by the
National Council on Compensation Insurance, by sector, company size, and year.
RESULTS: DIA's overall total injury rates were over twice those published by the
Bureau of Labor Statistics (BLS) for the construction industry for each year of
DIA construction. Differences in LWT injury rates were more modest. Total injury
rates were also at least twice BLS's rates for all contractor sizes. The injury
rate pattern by company size at DIA differed from BLS's in that small firms had
injury rates that were lower than or comparable to most other size categories;
BLS's rates for small firms were lower than those for all but the very largest
(250 or more employees) contractors. DIA's total workers' compensation (WC)
payment rate of $7.06 per $100 payroll was only 11% higher than Colorado-specific
expected loss rates reported by the National Council on Compensation Insurance.
DISCUSSION: Complete reporting, facilitated by the existence of a single WC plan,
an on-sites medical clinic, and designated medical providers, yielded injury
rates significantly higher than previously reported. The relatively small
difference between DIA payment rates significantly higher than previously that
the discrepancy between DIA's injury rates and national estimates is due to
underreporting of non-LWT injuries of the BLS. The burden of on-site work-related
construction injury may be higher and more costly than has been evident from
national data.
PMID- 9651620
TI - Risk factors for injury among construction workers at Denver International
Airport.
AB - BACKGROUND: The Denver International Airport construction project provided a rare
opportunity to identify risk factors for injury on a large construction project
for which 769 contractors were hired to complete 2,843 construction contracts.
Workers' compensation claims and payroll data for individual contracts were
recorded in an administrative database developed by the project's Owner
Controlled Insurance Program. METHODS: From claims andy payroll data linked with
employee demographic information, we calculated injury rates per 200,000 person
hours by contract and over contract characteristics of interest. We used Poisson
regression models to examine contract-specific risk factors in relation to total
injuries, lost-work-time (LWT), and non-LWT injuries. We included contract
specific expected loss rates (ELRs) in the model to control for prevailing risk
of work and used logistic regression methods to determine the association between
LWT and non-LWT injuries on contracts. RESULTS: Injury rates were highest during
the first year of construction, at the beginning of contracts, and among older
workers. Risk for total and non-LWT injuries was elevated for building
construction contracts, contract for special trades companies (SIC 17), contracts
with payrolls over $1 million, and those with overtime payrolls greater than 20%.
Risk for LWT injuries only was increased for site development contracts and
contract starting in the first year of construction. Contracts experiencing one
or more minor injuries were four times as likely to have at least one major
injury (OR = 4.0, 95% CI (2.9, 5.5)). CONCLUSIONS: Enhancement of DIA's safety
infrastructure during the second year of construction appears to have been
effective in reducing serious (LWT) injures. The absence of correlation between
injury rates among contracts belonging to the same company suggest that targeting
of safety resources at the level of the contract may be an effective approach to
injury prevention. Interventions focused on high-risk contracts, including those
with considerable overtime work, contracts held by special trades contractors
(SIC 17), and contracts belonging to small and mid-sized companies, and on high
risk workers, such as those new to a construction site or new to a contract may
reduce injury burden on large construction sites. The join occurrence of minor
and major injuries on a contract level suggests that surveillance of minor
injuries may be useful in identifying opportunities for prevention of major
injures.
PMID- 9651621
TI - Occupational injuries among adolescents in Washington State, 1988-1991.
AB - BACKGROUND: To characterize work-related injuries and illnesses in minors.
METHODS: We analyzed Washington State workers' compensation claims from 1988
through 1991. RESULTS: There were 17,800 claims among adolescents from age 11
through 17 years accepted in the 4-year period, including three occupational
fatalities, 22 amputations, and 464 fractures; 89% of all injuries occurred among
the 16- and 17-year-olds. Claims were most frequent in restaurants, food stores,
service industry, other retail and wholesale trade, and agriculture. Washington
State census data were used for denominator in calculating injury rates for
adolescents and adults. The crude injury rate for 16- and 17-year-olds employed
at the time of the census was similar to that seen among adults (9.0 vs 10.4 per
100 workers), despite that minors work fewer hours per year. The rate among boys
was almost twice that seen among girls (11.7 vs. 6.4 per 100 workers). Highest
rates, per 100 workers, were in public administration (27.0), construction
(21.1), agriculture (11.4), and restaurants (11.0). Using census data for those
working anytime over the course of the year and adjusted for the number of hours
worked, the injury rate for 16- and 17-year-olds was 19.4/100 full time
equivalents compared with 10.6 of 100 full-time equivalents for adults. Most
injuries were lacerations, sprains and strains, contusions, and burns.
CONCLUSIONS: Public health policy and injury prevention strategies for working
adolescents should be developed and implemented.
PMID- 9651622
TI - Evaluation of narrative text for case finding: the need for accuracy measurement.
AB - This article reviews the analysis of a narrative text electronic search technique
being used in the insurance industry. We reviewed a previously published study of
motor vehicle crashes in roadway construction workzones as well as additional
data supplied by the authors with respect to the methods of keyword selection.
The narrative text search technique was evaluated with decision statistics and
was found to have a sensitivity of 92.3%, 95% confidence interval 67.5%-99.6%.
This range of sensitivity, at its most extreme value, led to a 32.5%
underestimation of claims prevalence. Furthermore, because the electronic search
developed two classification categories from a limited text field (approximately
20 words), only half of the cases had at least one classification. Systematic
error estimates were used to obtain true population proportions for crash
characteristics, revealing significant underestimations in costs. This analysis
highlights the need for investigators to apply decision statistics to narrative
text searching techniques when they are used essentially as diagnostic test
procedures on insurance claims datasets.
PMID- 9651623
TI - Pathomechanisms and pathophysiology of isocyanate-induced diseases--summary of
present knowledge.
AB - During recent years in Western countries, diisocyanates are one of the main
causes of occupational asthma. The mechanism of diisocyanate-induced asthma is
still unknown but recent evidence suggests immunological mechanisms, including
cell-mediated immune responses. Immune responses to isocyanates may result in
different illnesses, cell- and/or antibody-mediated entities. In addition,
irritative, toxic, and mutagenic effects may occur. This review summarizes
current knowledge of the pathomechanisms, including immunological and
nonimmunological (mutagenic and genotoxic) aspects of isocyanate disorders.
PMID- 9651624
TI - Associations between several sites of cancer and occupational exposure to
benzene, toluene, xylene, and styrene: results of a case-control study in
Montreal.
AB - BACKGROUND: Except for the leukemogenic effects of benzene, there is inadequate
or sparse evidence on the carcinogenicity of the most common monocyclic aromatic
hydrocarbons. The purpose of this study was to generate hypotheses on
associations between exposure to benzene, toluene, xylene, and styrene and
various common types of cancer. METHODS: In the context of a population-based
case-control study carried out in Montreal, 3,730 cancer patients (15 types of
cancers, not including leukemia) and 533 population controls were interviewed,
and their job histories were translated by a team of experts into occupational
exposures, including benzene, toluene, xylene, and styrene. In the present
analysis, exposure to these substances was compared between each case series and
a control group pooling selected cancer patients and population controls, using
logistic regression analysis. RESULTS: Exposure levels were low for most exposed
subjects, and there was a high correlation between exposure to benzene, toluene
and xylene. For most sites of cancer there was no evidence of excess risk due to
these substances. However, limited evidence of increased risk was found for the
following associations: esophagus-toluene, colon-xylene, rectum-toluene, rectum
xylene and rectum-styrene. CONCLUSIONS: These latter observations warrant further
investigation.
PMID- 9651625
TI - Cancer incidence among Ontario police officers.
AB - The National Institute for Occupational Safety and Health (NIOSH) published a
report in 1995 suggesting the possibility of increased incidence of testicular
cancer, leukemia, and cancers of the brain, eye, and skin among police officers
working with traffic radar. NIOSH recommended epidemiologic study of the issue.
This report presents the results of a retrospective cohort cancer incidence study
among 22,197 officers employed by 83 Ontario police departments. The standardized
incidence ration (SIR) for all tumors sites was 0.9% (95% confidence interval
[CI] = 0.83-0.98). There was an increased incidence of testicular cancer (SIR =
1.3, 90% CI = 0.9-1.8) and melanoma skin cancer (SIR = 1.45, 90% CI = 1.1-1.9).
These anatomical sites might absorb energy from radar units, but at this time the
author has no information about individual exposures to radar emissions, and it
is not possible to draw etiologic conclusions. Nested case-control studies are
planned to assess individual radar exposures.
PMID- 9651626
TI - Work-related respiratory symptoms and lung function in New Zealand mussel
openers.
AB - Our objectives were to measure the prevalence of work-related and nonwork-related
respiratory symptoms in a group of New Zealand mussel openers who open green
lipped mussels, and to relate these to demographic factors, work history, smoking
history, and pulmonary function measurements. A cross-section study of
respiratory symptoms and lung function was performed on 224 New Zealand mussel
openers (99.6% of the study population) at nine work sites. In addition, peak
expiratory flow (PEF) change across-shift was measured at one work site in 19
workers. The mean age of all mussel openers was 33.4 years and the mean duration
of mussel opening was 5.0 years; 25% were male, 54.7% were current smokers, and
13.9% were ex-smokers. The reported symptom prevalences were: any wheeze, 35%;
work-related wheeze, 23%; any chest tightness, 30.5%; work-related chest
tightness, 20.2% (work-related symptoms were defined as symptoms improving on
rest days or worse at work). Seventy-two mussel openers (32.3%) answered
positively to at least 1 of 4 questions concerning work-related symptoms. The
mean predicted FEV1 (SD) for this group was 74.3% (14.5), and the mean predicted
FVC (SD) was 79.2 (16.0). Nineteen workers completed serial PEF, and the mean
percentage change was +1.5% at 7 hr, but 8 workers had falls ranging between 1.1
14% after either 1 or 7 hr of work. Duration of mussel opening of greater than 2
years, but less than 7 years (OR = 2.29; 95% CI, 1.07-4.91), and duration of
mussel opening greater than 7 years (OR = 3.72; 95% CI, 1.52-9.11), were
significant predictors of work-related respiratory symptoms. Female sex (OR =
1.73; 95% CI, 0.83-3.60) was also associated with the presence of work-related
symptoms. No relationship was found with measured hygiene parameters of cleaning
agents used. In conclusions, duration of work as a mussel opener was associated
with the present of work-related respiratory symptoms, after adjustment of age,
sex, and smoking habit. There were marked abnormalities in mean FEV1 and FVC,
although no consistent changes across working shift were noted.
PMID- 9651627
TI - Dermal and respiratory sensitization to chromate in a cement floorer.
AB - BACKGROUND: To report a well-documented case of both allergic contact dermatitis
and occupational asthma due to chromate exposure in a 48-year-old floorer.
METHODS AND RESULTS: A 48-year-old floorer, occupationally exposed to cement and
with a documented chromate contact dermatitis, reported dyspnea and wheezing
after work. These conditions were demonstrated by self-measured sequential peak
expiratory flows. A first bronchial provocation (BPT) with potassium dichromate
(K2Cr2O7) (0.3% nebulized for a total of 60 minutes) led to pronounced and
sustained decreases in forced expiratory volume in 1 second (FEV1) and forced
vital capacity, accompanied by pruritus, a decrease in arterial PO2, a slight
rise in temperature, and peripheral blood leukocytosis. (This concentration of
K2Cr2O7 is not recommended for BPT). Bronchoalveolar lavage performed 2 days
later showed 18% eosinophils. Tow years later, a BPT with a lower dose of K2Cr2O7
(0.01% for the total of 31 min) led to an "earl late" reaction (FEV1 dropped by
195 compared with the initial FEV1 value), accompanied by pruritus. A BPT with
dry cement, containing 12 ppm hexavalent chromium, was borderline (FEV1 dropped
by 13%), and a similar result (FEV1 dropped by 14%) was obtained after smoking
five cigarettes, laced with 10 mg of cement per cigarette. CONCLUSIONS: This
report illustrates that a subject, with allergic contact dermatitis to chromates,
may develop a respiratory allergic reaction to an airborne source of this metal.
The main novelty of our report is that the smoking of cigarettes contaminated
with cement may have been significant factor in the causation or elicitation of
these reactions.
PMID- 9651628
TI - Evaluation of workers exposed to dust containing hard metals and aluminum oxide.
AB - BACKGROUND: Fourteen worker exposed to hard metals and aluminum oxide were
evaluated. METHODS: Six heavily exposed workers underwent bronchoscopy and
bronchoalveolar lavage, and five workers underwent transbronchial biopsy.
RESULTS: Microchemical analysis of transbronchial biopsies showed a high lung
burden of exogenous particles, especially metal related to their hard metals
exposure. Lung tissue and cellular changes, which were associated with exposure
to hard metal and aluminum oxide, corresponded well with the microanalytic test
results. CONCLUSIONS: Three workers had at biopsy diffuse interstitial
inflammatory changes: two of them were asymptomatic with normal chest X-ray
films, and one had clinically evident disease with severe giant cell
inflammation. Two other workers showed focal inflammation. The worker showing
clinical disease and one asymptomatic worker with interstitial inflammatory
changes had evaluated bronchoalveolar lavage fluid-eosinophilia counts. These two
were father (with clinical disease) and son (asymptomatic).
PMID- 9651629
TI - Toxigenic fungi in a water-damaged building: an intervention study.
AB - In an investigation of health complaints among employees of a water-damaged
office building, the environment showed evidence of fungal contamination with the
isolation of Stachybotrys chartarum in one of five bulk samples tested for fungal
growth. In response, a public health official recommended that employees be
relocated from the building. Employees were subsequently moved to a different
environment. A focused environmental investigation of microbial growth within the
building followed, revealing moderate to high levels of fungi (Penicillium,
Aspergillus versicolor) and bacteria in bulk and surface samples. S. Chartarum
was identified in one of 19 (5%) environmental samples using Czapek agar. A
health survey of building occupants revealed a high prevalence of multiple
symptoms, with the predominance of neurobehavioral and upper respiratory tract
complaints. The majority of symptoms were significantly less prevalent after
relocation from the water-damaged environment. The initial hypothesis that
exposure to toxigenic fungi was responsible for the high prevalence of reported
symptoms is difficult to investigate and confirm given the current limits of
epidemiological knowledge regarding exposure to these organisms and building
related illness. Future interventions where mycotoxin exposure is suspected
should emphasize the importance of risk assessment and risk communication.
PMID- 9651630
TI - Lead exposure in a developmentally disabled workforce.
AB - Over-exposure to lead was identified among developmentally disabled workers
engage in furniture refinishing at two separate sites. The index case was
identified at the first site by a public health nurse assigned to provide care to
some of the workers. Referral to a regional occupational health clinic initiated
an exposure assessment and medical consultation at both work sites. Blood lead
levels (BLLs) among sanders and helpers at site A averaged 60 micrograms per
deciliter of blood (mcg/dl). At site B, BLLs were lower, but 6 individuals had
BLLs greater than mcg/dl. Hand sanding of chemically stripped wood previously
coated with lead-based paint was determined to be the exposure source. These
incidents document potential lead overexposure in an underecognized setting. They
also emphasize the importance of incorporating a workplace health risk assessment
in the process of placing and protecting the developmentally disabled on the job.
PMID- 9651631
TI - Asbestos-related x-ray changes in foundry workers.
AB - Michigan has a statewide mandatory occupational disease reporting system. As part
of that system, reports are received from hospital, physicians, death
certificates, the worker's compensation bureau, and company medical departments.
Based on this reporting, the State of Michigan has a special emphasis program for
the surveillance of silicosis, a known disease outcome among foundry workers.
From 1985-1996, 115 cases reported to the State Surveillance System as silicosis,
pneumoconiosis not specified, or pulmonary fibrosis were reclassified as having
asbestos related x-ray changes after a B-reader interpretation of each case's
chest x-ray. During this same period there were an additional 697 reports
confirmed as silicosis and 6,724 cases reported to the surveillance system as
asbestosis. Among the 115 reports reclassified as having asbestos-related x-ray
changes without evidence of silicosis-related x-ray changes, 54 had worked in
foundries. Only 7 (14.8%) of these individuals had their primary work in
maintenance in the foundry; 40 (85.1%) had their primary foundry work in a
production job; and for 10 individuals the occupation was not known. Asbestos has
been used in foundries on pipe laggings, boiler coverings, as insulation in fan
housings, in gloves, aprons and curtains, as insulation in cupolas, and in ladles
and insulation in sand molds. Clinicians caring for foundry workers need to be
aware that asbestos-related x-ray changes are not uncommon in this population and
asbestos exposure should be considered as one of the carcinogens contributing to
the known increased risk of lung cancer among foundry workers.
PMID- 9651633
TI - Smokers' misperceptions of light and ultra-light cigarettes may keep them
smoking.
AB - INTRODUCTION: This study examined smokers' understanding of the relative tar
deliveries of Ultra-light, Light, and Regular cigarettes, reasons for smoking
Ultra-light/Light cigarettes, and the likelihood of both quitting smoking and
switching to Regular cigarettes if they came to learn that one Ultra-light/Light
cigarette gave the same amount of tar as one Regular cigarette. DESIGN: Ten- to
fifteen-minute random-digit-dialed, computer-assisted telephone interviews (CATI)
were conducted with both a national probability sample (n = 788) and a state
random sample (n = 266) of daily smokers over the age of 18. RESULTS: Less than
10% of smokers in the national sample and only 14% of smokers in the state sample
knew that one Light cigarette could give the same amount of tar as one Regular
cigarette. Less than 10% of smokers in the state sample knew that one Ultra-light
cigarette could give the same amount of tar as one Regular cigarette. Thirty-two
percent of the Light and 26% of the Ultra-light smokers in the national sample,
and 27% of Light and 25% of Ultra-light smokers in the state sample, said they
would be likely to quit smoking if they learned one Light/Ultra-light equaled one
Regular. CONCLUSION: Many Light and Ultra-light smokers are smoking these
cigarettes to reduce the risks of smoking and/or as a step toward quitting.
However, these smokers are unaware that one Ultra-light/Light cigarette can give
them the same amount of tar and nicotine as one Regular cigarette. Many of the
Ultra-light/Light smokers sampled in this study stated that they would be likely
to quit if they knew this information. Mistaken beliefs about low-yield brands
are reducing intentions to quit smoking.
PMID- 9651632
TI - Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational
risk of hepatitis B virus infection.
AB - OBJECTIVE: To assess risk factors for decreased immunogenicity among adults
vaccinated with hepatitis B vaccine and to determine the importance of
differences in immunogenicity between vaccines among health care workers (HCWs).
DESIGN: Randomized clinical trial and decision analysis. PARTICIPANTS: HCSw. MAIN
OUTCOME MEASURES: Development of seroprotective levels of antibody to hepatitis B
surface antigen (anti-HBs) and the number of expected chronic hepatitis B virus
(HBV) infections associated with lack of protection. RESULTS: Overall, 88% of
HCWs developed seroprotection. Risk factors associated with failure to develop
seroprotection included increasing age, obesity, smoking and male gender (P <
.05). Presence of a chronic disease was associated with lack of seroprotection
only among persons > or = 40 years of age (P < .05). The two vaccines studied
differed in their overall seroprotection rates (90% vs. 86%; P < .05), however,
this difference was restricted to persons > or = 40 years of age (87% vs. 81%; P
< .01). Among HCWs > or = 40 years of age, the decision analysis found 44
(0.34/100,000 person-years) excess chronic HBV infections over the working life
of the cohort associated with use of the less immunogenic vaccine compared to the
other. CONCLUSIONS: He patitis B vaccines are highly immunogenic, but have
decreased immunogenicity associated with increasing age, obesity, smoking, and
male gender; and among older adults, the presence of a chronic disease. One of
the two available vaccines is more immunogenic among older adults; however, this
finding has little clinical or public health importance. Hepatitis B vaccines
should be administered to persons at occupational risk for HBV infection early in
their career, preferably while they are still in their training.
PMID- 9651634
TI - Factors associated with smoking among children and adolescents in Connecticut.
AB - INTRODUCTION: The age of smoking initiation has dropped over the past four
decades. Since behaviors and attitudes adopted in late childhood or early
adolescence predict future smoking, it is important to understand the smoking and
other risk-taking behaviors and attitudes of children aged 12 and younger. The
goal of the analyses presented here was to describe behavioral and attitudinal
factors associated with smoking among elementary school (grades 4-6), middle
school (grade 7-8), and high school (grades 9-12) students in Connecticut.
METHODS: We have used data from 8 years (1988-1996) of an anonymous, self
administered health risk appraisal survey given to children and adolescents in
self-selected public and private schools. We compared the proportion of smokers
and nonsmokers who reported various behaviors and attitudes and compared them
with the chi-square test. RESULTS: Fifteen percent (n = 4,884) of the total
population (n = 31, 861) were current smokers. At all grade levels, current
smokers were more likely than nonsmokers to engage in risk-taking behaviors, and
to report more stress and depression. Indicators of risk-taking and stress were
also associated with the intent to smoke among children in grades 4-6.
CONCLUSIONS: Smoking occurs within the context of other risk-taking behavior and
psychological distress, among both children and older adolescents. Our data
provide support for the idea of early identification and targeting of children at
high risk of smoking in elementary school, possibly as early as grade four.
PMID- 9651635
TI - Smoking relapse prevention during pregnancy. A trial of coordinated advice from
physicians and individual counseling.
AB - INTRODUCTION: Our objective was to examine the efficacy of physicians' advice and
referral to individual counseling in preventing relapse to smoking among women
who were smokers early in pregnancy, but quit prior to their first prenatal
visit. DESIGN: A randomized controlled trial of prompted physician's advice and
individual relapse prevention counseling during pregnancy compared to usual
physician advice. Smoking status was assessed by self-report, exhaled carbon
monoxide, and urinary cotinine during pregnancy and by self-report 1 year
postpartum. RESULTS: There were no significant differences in relapse rates
between the intervention and usual-care groups during pregnancy, nor at 1 year
postpartum. Relapse rates were 23% in both groups at the 36-week visit, and 32%
and 22%, respectively, 1 year postpartum. Younger age, higher motivation to
resume smoking, and higher levels of exhaled carbon monoxide at the first
prenatal visit were predictive of relapse to smoking during pregnancy. With the
conservative assumption that all those lost to follow-up relapsed, the combined 1
year postpartum relapse rate, 51%, was 17 percentage points lower than we
observed in an earlier relapse prevention trial, and 15 percentage points lower
than that observed nationally a decade earlier. CONCLUSION: Prompting physicians
to provide supportive advice combined with referral to individual relapse
prevention counseling did not reduce smoking relapse rates during pregnancy, or
postpartum. However, the level of attention paid to smoking by physicians in both
intervention and usual-care groups during pregnancy may have contributed to the
relatively low relapse rates seen 1-year postpartum.
PMID- 9651636
TI - Por La Vida model intervention enhances use of cancer screening tests among
Latinas.
AB - OBJECTIVE: To describe the short-term impact of the intervention known as Por La
Vida (PLV) on cancer screening for Latinas in San Diego, California. METHODS:
Thirty-six lay community workers (consejeras) were recruited and trained to
conduct educational group sessions. Each consejera recruited approximately 14
peers from the community to participate in the program. The consejeras were
randomly assigned to either a twelve-week cancer screening intervention group or
a control group in which they participated in an equally engaging program
entitled "Community Living Skills." Pre- and post-intervention self-report
information was obtained from project participants on the use of cancer screening
examinations. Outcome measures were changes in the percentages of women who had
breast and cervical cancer screening test within the past year before and after
the intervention occurred. Experimental and control groups were compared using t
tests. Analyses were conducted using both consejeras and participants as the unit
of analysis. RESULTS: The increase in the use of the cancer screening test was
higher in the PLV cancer intervention group in comparison to women in the
community living skills control group. CONCLUSIONS: Key to the PLV intervention
model is the identification of natural helpers in the Latino community and their
subsequent training in intervention based on social learning theory using
culturally appropriate educational materials. The model is an effective and
viable approach for increasing the use of cancer screening tests in Latinas of
low socioeconomic level and low level of acculturation.
PMID- 9651637
TI - Increased drug use among old-for-grade and dropout urban adolescents.
AB - INTRODUCTION: In tracking the epidemic of drug use in our communities, much
emphasis has been placed on identifying predictive variables. In this study, we
examine the relationship between drug use and school progress among a sample of
inner-city adolescents. METHODS: A blinded, anonymous questionnaire covering a
variety of health risk behaviors was administered to 1,720 adolescent patients
who visited our outpatient clinic. Participants were classified as age
appropriate for last school grade completed, older than normal for grade, or as a
dropout. A urine specimen was also collected in a blinded, anonymous fashion from
each participant, and tested for five common substances of abuse. RESULTS: Nearly
12% of participants tested positive for drugs. Participants who were old for
grade were over 40% more likely to be positive for drugs than grade-appropriate
respondents, while school dropouts were more than twice as likely to test
positive. CONCLUSIONS: These results demonstrate that being old-for-grade (OFG)
and being a dropout in our population are markers for being at higher risk of
substance abuse.
PMID- 9651638
TI - U.S. women physicians' residential radon testing practices.
AB - INTRODUCTION: These analyses were designed to elucidate U.S. physicians'
perception of residential radon risk, as measured by the prevalence of
residential radon testing using a representative sample of U.S. women physicians
from the Women Physicians' Health Study database. In addition, characteristics of
women physicians who were more likely to have conducted a residential radon test
were identified. METHODS: A random sample (n = 4,501 respondents) of U.S. women
physicians aged 30 to 70 was obtained in the Women Physicians' Health Study.
Analyses were conducted using SUDAAN. RESULTS: The overall prevalence of
residential radon testing among respondents was 18%, 2- to 6-fold higher than any
estimate of residential radon testing in the general population. The strongest
relationship with radon testing observed through logistic regression was with
marital status; age, ethnicity, and region of residence were also related.
CONCLUSION: The study demonstrates that although U.S. women physicians are more
likely to have conducted a personal residential radon test than the general
population, 82% report not having done so. Increasing the awareness of physicians
about the health risks associated with prolonged radon exposure will be essential
if they are to play a role in addressing this important public health problem.
PMID- 9651639
TI - The influence of psychosocial factors, alcohol, drug use on African-American
women's high-risk sexual behavior.
AB - OBJECTIVE: The present study examines psychosocial and behavioral influences,
particularly drug and alcohol use, as correlates of inconsistent condom use and
having multiple sexual partners during the past months among African-American
women. METHODS: The cross-sectional study, conducted between May and June 1996,
recruited a convenience sample of 180 African-American women in Birmingham,
Alabama. Women completed a face-to-face interview that assessed alcohol and drug
use, sexual behaviors, depression, condom use, and negotiation skills. RESULTS:
The majority of women, 51.6% (n = 93), had used either alcohol or drugs during
the previous month. Many women, 31.1%, consumed alcohol, 18.3% used marijuana,
and 8.3% had smoked crack within the past month. Nearly 42.7% of women used
condoms inconsistently in the past month and 13.3% of women had multiple sexual
partners within the past month. A logistic regression model predicting
inconsistent condom use indicated that women were less likely to use condoms if
they consumed alcohol between 20 and 30 days of the month (OR = 2.8, 90% CI = 1.3
5.9) and if they had not negotiated condom use (OR = 32.4, 90% CI = 7.9-131.6).
The logistic regression model predicting multiple sexual partners indicated that
women were more likely to have multiple sexual partners if they had smoked crack
in the past month (OR = 5.3, 90% CI = 1.6-18.2). CONCLUSION: HIV sexual risk
reduction interventions for African-American women need to address the
overlapping epidemics of drugs, alcohol, and STDs. Additionally, HIV sexual risk
reduction efforts should be incorporated into existing drug and alcohol treatment
programs and STD clinics.
PMID- 9651640
TI - Prevention of elderly suicide. Physicians' assessment of firearm availability.
AB - INTRODUCTION: Physicians have a unique role to play in the prevention of elder
suicide, yet they may not be sufficiently attentive to the prominence of firearms
in the rising trend in suicide by elder persons. This study sought to examine the
extent to which physicians inquired about firearms with their depressed and
suicidal elderly patients and further identified factors associated with
physicians' likelihood of asking about firearms. METHODS: A probability sample of
300 primary care physicians in Illinois was drawn from the American Medical
Association Physician Masterfile. Physicians were chosen from the specialties
most likely to be involved with elderly persons: internal medicine and family
practice. A mailed questionnaire yielded a 63% response rate. RESULTS: Although
they were treating depressed and suicidal older patients, a sizable proportion of
the respondents (42%) reported that they did not ask such patients or their
family members whether they had access to a firearm. Several factors
distinguished physicians who assessed for firearms from those who did not. The
most salient predictors were: continuing medical education training in suicide
risk assessment, expertise in geriatric mental health, confidence in diagnosing
depression, having a patient mention suicide in the past year, and indicating
patient reluctance as a barrier to mental health treatment. DISCUSSION:
Physicians working with depressed and suicidal elderly persons need to be
informed about the prevalence of elder suicide and about the likelihood of
elderly persons using firearms as a method of suicide. Effective suicide
prevention will require physician training that directly addresses geriatric
mental health and firearm suicide, in particular, at the student, residency, and
continuing education levels.
PMID- 9651641
TI - Competencies for population-based clinical managers. A survey of managed care
medical directors.
AB - BACKGROUND: The evolution of American health care into integrated systems of
delivery and finance requires a specialized set of population-based skills for
physicians. The field of preventive medicine represents one source of this
expertise. Specific competencies for the emerging area of managerial medicine
have not been well delineated. METHODS: Using concept documents from the
Residency Review Committee for Preventive Medicine and the American Board of
Preventive Medicine, a list of proposed competencies for managerial medicine was
identified. Surveys were mailed to medical directors of all members of the
American Association of Health Plans and to a random sample of diplomates of the
American Board of Preventive Medicine. Respondents were asked to rate the
importance of these competencies for a population-oriented clinician manager.
RESULTS: Areas rated highly by medical directors included health services
research (including outcome research), quality assurance and improvement, health
risk assessment and reduction, programmatic skills, and clinical preventive
skills. Responses from preventive medicine specialists were similar, but placed
lower emphasis on these skills. CONCLUSION: Despite its limited response rate,
this survey may be useful in the implementation of specialty training in
managerial medicine. Residency training programs may choose to emphasize specific
content area that reflect the priorities expressed by physicians actively
involved in management.
PMID- 9651642
TI - Medical directors, managed care, and population medicine competencies. Old wine
in new bottles.
PMID- 9651643
TI - Hepatitis B immunization in health care workers. Dealing with vaccine
nonresponse.
PMID- 9651644
TI - Harm-reduction approaches to smoking. The need for data.
PMID- 9651645
TI - The strength of the relation between prenatal care and low birthweight.
PMID- 9651646
TI - American College of Preventive Medicine practice policy. Screening for prostate
cancer in American men.
PMID- 9651647
TI - Cranial allometry and geographic variation in slow lorises (Nycticebus)
AB - A series of 20 craniodental measurements was obtained for two sister taxa:
Nycticebus coucang (common slow loris) and N. pygmaeus (pygmy slow loris).
Multivariate analysis of variance was performed with adult data to describe
patterns of subspecific and specific variation in this genus. The geometric mean
of adult cranial dimensions was compared to field data on latitudinal coordinates
for available specimens to investigate if size variation in Nycticebus is clinal
in nature. Ontogenetic series for larger-bodied N. coucang and smaller-bodied N.
pygmaeus were compared to test the hypothesis that species and subspecific
variation in skull form results from the differential extension of common
patterns of relative growth. A MANOVA provides independent support of Groves's
[pp. 44-53 in Proceedings of the Third International Congress on Primatology,
Vol. 1 (Basel: S. Karger), in 1971)] classification of Nycticebus into two
species, with four subspecies in the common slow loris and one form of the pygmy
slow loris. Within N. coucang, cranial proportions for all four subspecies are
ontogenetically scaled, and size differentiation is mainly clinal (Bergmann's
Rule). N. c. bengalensis represents the most northerly disposed and the largest
form. N. c. javanicus represents the next-largest form and is located in a
southerly direction the next-farthest away from the equator. N. c. coucang and N.
c. menagensis are both equatorial; however, the latter subspecies is the
smallest. A genetic basis for some of the taxonomic variation between N. c.
coucang and N. c. menagensis is supported by such nonclinal variation in body
size. Variation in the presence/absence of I2 is not size-related but rather
tracks geographic proximity and isolating factors which predate the most recent
inundation of the Sunda Shelf. Although they inhabit a nonequatorial environment,
pygmy slow lorises are the smallest of all Nycticebus. As N. pygmaeus is
sympatric with N. c. bengalensis, the largest slow loris, it appears that the
evolution of its smaller body size represents a case of character displacement.
Unlike N. coucang, skull size becomes significantly smaller in more northern N.
pygmaeus. This may also reflect character displacement between sympatric sister
taxa underlain by a cline-dependent ecological factor which is marked in more
northerly latitudes. On the other hand, the negative correlation between body
size and latitude in N. pygmaeus could be due to the influence of nonprimate
fauna, such as predators, which themselves evince a similar clinal pattern.
Analyses of relative growth indicate that skull proportions in the two species of
Nycticebus are ontogenetically scaled in two-thirds of the cases. All but one of
the seven comparisons (interorbital breadth) which do not indicate ontogenetic
scaling represent part of the masticatory complex. This likely reflects a
reorganization of N. pygmaeus maxillomandibular proportions linked to smaller
size and changes in diet.
PMID- 9651648
TI - Differences in stress reactivity of laboratory macaques measured by heart period
and respiratory sinus arrhythmia.
AB - Some laboratory primates are more likely than others to react to anxiety
provoking stressors. Individuals that overreact to stressors may experience
diminished psychological well-being and would be inappropriate for some
experiments. The differences between reactive and nonreactive individuals may be
reflected in heart period and respiratory sinus arrhythmia (RSA). Using surface
electrodes and radio telemetry, we measured these two cardiac variables in seven
male and ten female singly caged longtailed macaques (Macaca fascicularis) when
they were exposed to two stressors, a sudden noise (whistle test) and an
unfamiliar technician wearing capture gloves (glove test). Behavior was
videotaped during both tests. For the whistle test, cardiac data were recorded
before, during, and after two 1 minute whistle blasts separated by 90 min. For
the glove test, data were recorded in 1 minute blocks every 8 minutes over 96
minutes before, during, and after 1 minute exposure to the gloved technician.
Heart period was decreased and RSA was suppressed during both the whistle and
glove exposures. After the whistle test, the cardiac activity of most subjects
returned to baseline levels within 10 minutes. The glove test produced more
extended suppression, with greater individual differences, than the whistle test.
There were greater individual differences in RSA than in heart period. These
enhanced individual differences were used to define stress reactors that differed
from nonreactors in their cardiac data profiles. Of 16 subjects that completed
the glove test, five were identified as reactors.
PMID- 9651649
TI - Feeding ecology of the black howler monkey (Alouatta pigra) in northern Belize.
AB - We studied the feeding ecology of the black howler monkey (Alouatta pigra) from
March 1994 to April 1995 in the Community Baboon Sanctuary in northern Belize,
Central America. Activity and diet composition were recorded using continuous
focal animal sampling. Diet composition was compared with the relative abundance
of plant parts eaten by the howlers within the study site. The study animals
spent an average of 24.4% of their time feeding, 61.9% resting, and approximately
9.8% traveling. In contrast to previously published reports on A. pigra, we found
the diet composition to be similar to that of other Alouatta species (conforming
to the folivore/frugivore profile), with 41% of feeding time spent eating fruit,
45% foliage, and 11% flowers. This contrast may indicate a wide degree of dietary
flexibility that allows A. pigra to inhabit a variety of habitat types. We
suggest that a high level of resource abundance throughout the year makes the
Community Baboon Sanctuary excellent habitat for Alouatta pigra.
PMID- 9651650
TI - Use of sleeping trees by black and white colobus monkeys (Colobus guereza) in the
Kakamega Forest, Kenya.
AB - Groups of black and white colobus monkeys, or guerezas (Colobus guereza),
observed in the Kakamega Forest, Kenya, had weak fidelity for sleeping sites.
Groups often slept in trees near commonly used food sources, which might reduce
the time and energetic costs of travel. Although the home range of each group
overlapped with four to seven others, groups seemed to avoid sleeping near other
groups, which would give them immediate and exclusive access to nearby food
sources in the morning. The number of times a species of tree was slept in was
positively correlated with its density. This may have occurred because so many
suitable sites were available that proximity to feeding trees could be obtained
whether or not groups slept in the feeding trees. Groups slept in tall trees,
which provide stable sleeping sites and which may provide protection from both
aerial and ground predators. Groups were more tightly clustered on nights with
greater visibility, which might reduce the risk of predation.
PMID- 9651651
TI - Topographical localization of iron in brains of the aged fat-tailed dwarf lemur
(Cheirogaleus medius) and gray lesser mouse lemur (Microcebus murinus).
AB - Iron deposits in the human brain are characteristic of normal aging but have also
been implicated in various neurodegenerative diseases. Among nonhuman primates,
strepsirhines are of particular interest because hemosiderosis has been
consistently observed in captive aged animals. In particular, the cheirogaleids,
because of their small size, rapid maturity, fecundity, and relatively short life
expectancy, are a useful model system for the study of normal and pathological
cerebral aging. This study was therefore undertaken to explore iron localization
in the brain of aged cheirogaleids (mouse and dwarf lemurs) with histochemistry
and magnetic resonance microscopy. Results obtained with both techniques were
comparable. There was no difference between old animals in the two species. The
young animals (3 years old) showed no iron deposits. In the old animals (8-15
years old), iron pigments were mainly localized in the globus pallidus, the
substantia nigra, the neocortical and cerebellar white matter, and anterior
forebrain structures, including the nucleus basalis of Meynert. This distribution
agrees with previous findings in monkeys and humans. In addition, we observed
iron in the thalamus of these aged non-human primates. Microscopic NMR images
clearly reveal many features seen with the histochemical procedure, and magnetic
resonance microscopy is a powerful method for visualizing age-related changes in
brain iron.
PMID- 9651652
TI - Presence of platelet-activating factor in squirrel monkey (Saimiri boliviensis)
spermatozoa: seasonal differences.
AB - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphoryl-choline)
(PAF) is a potent signaling phospholipid which has pleiotropic biological
properties in addition to platelet activation. PAF has been detected in the
spermatozoa in a number of species. The concentration of PAF is inversely related
to human spermatozoa quality. There are no reports on the presence of PAF in
nonhuman primate spermatozoa. Therefore, the primary objective of this study was
to determine if PAF is present in the spermatozoa from the squirrel monkey (which
is a seasonal breeder). A second objective was to determine if PAF levels change
from the breeding to the nonbreeding season. Endogenous lipids were extracted
from mature Bolivian squirrel monkeys (Saimiri boliviensis) spermatozoa and
assayed for the presence of PAF by [125I] radioimmunoassay. PAF was detected in
all samples assayed. PAF levels were significantly higher (P < 0.01) during the
breeding season (mean: 3.58 ng/10(6) spermatozoa) than the nonbreeding season
(mean: 0.76 ng/10(6) spermatozoa). The data demonstrate that PAF is present in
squirrel monkey spermatozoa, with higher levels found during the breeding season.
Additional studies are warranted to elucidate the role of PAF in spermatozoa
function.
PMID- 9651653
TI - Responses of gibbons (Hylobates lar) to their mirror images.
AB - Nine gibbons (Hylobates lar) and one gibbon-siamang crossbreed were observed
during exposure to their mirror images over two 30 minute baseline condition
periods (mirror off) and four 30 minute treatment condition periods (mirror on).
Greater frequencies and durations of gazing at the mirror and mirror-contingent
behaviors were noted during the reflective conditions than for nonreflective
conditions. Despite two subjects' apparent use of the mirror to view body parts
otherwise not visible to them, no subjects passed a modified mark test. One
subject exhibited limited aggressive displays toward the mirror, but no subjects
exhibited abnormal behaviors in the presence of the mirror. The results expand on
and confirm similar findings by Lethmate and Ducker [Zeitschrift fur
Tierpsychologie 33:248-269, 1973].
PMID- 9651654
TI - Sex-selection of human spermatozoa: evolution of current techniques and
applications.
AB - Methods claiming to achieve sex selection by sperm sorting have existed for many
years. Numerous applications for safe and effective selection procedures exist in
current clinical practice, as sex-linked conditions could be theoretically
eliminated by use of appropriate sperm for fertilization or insemination. Use of
such techniques could also address the need to effect family balancing for some
couples. Modern preconception sex-selection methods may be classified into two
general types: those that attempt to segregate spermatozoa on the basis of subtle
physical or kinetic features, and those that rely on distinctive nuclear
characteristics unique either to X- or Y-chromosome bearing sperm. Laboratories
providing sperm sexing using the former method have been available for some
years, although the associated efficiency and reproducibility are controversial.
Sex selection of spermatozoa by chromatin differences has been shown to achieve
significant enrichment of X- or Y-chromosome bearing sperm, but clinical
experience in humans is limited. The fundamental elements of the two approaches
introduced here are reviewed and compared. Selected key historical concepts in
sex selection by sperm sorting are outlined, followed by a summary of promising
areas for future research.
PMID- 9651655
TI - Effect of clomiphene citrate on ovulation after treatment withdrawal.
AB - The effect of clomiphene citrate (CC) on ovarian function in cycles subsequent to
treatment withdrawal was studied. Thirty two out of 45 patients with anovulation
due to polycystic ovarian syndrome (PCOS) and with no other factor affecting
fertility who got pregnant were included. All patients received CC to induce
ovulation. Pregnancies in CC treated cycles and after treatment were recorded.
Twenty pregnancies were achieved during CC treated cycles and 12 in the cycles
after it was withdrawn. In the latter group, eight pregnancies were achieved in
the cycle following CC therapy, and four in the second subsequent cycle. In
relation to pregnancy complications no significant statistical differences were
found between the group of patients who became pregnant during the stimulation
cycles and in the cycles after CC.
PMID- 9651656
TI - Relation between bone mineral content and clinical, hormonal and biochemical
parameters in postmenopausal women.
AB - We studied factors related to bone mass after a natural or surgical menopause in
73 healthy women attending the menopause clinic of a university hospital. In the
natural menopause group we found inverse correlations between bone mineral
density (BMD) vs. menopausal duration; BMD vs. body mass index (BMI) and BMI vs.
inorganic phosphate (Pi), borderline correlations between weight vs. thyroxin
(T4) and weight vs. luteinising hormone (LH) and a positive correlation between
androstenedione (D4A) vs. urinary calcium (Uca). In the surgical menopause group
we found some negative correlations (BMD vs. menopausal duration, BMI vs. Pi; BMI
vs. dehydroepiandrosterone sulphate (DS), weight vs. DS and cortisol vs. Uca) and
some positive correlations (BMD vs. free testosterone (fT), BMD vs. calcium (Ca),
and BMD vs. Uca). We concluded that the serum hormone levels we measured were not
useful markers of current bone mineral status.
PMID- 9651657
TI - Human leucocyte antigens in pregnant women with pre-eclampsia associated with
intrauterine growth retardation and in normal controls.
AB - OBJECTIVE: To investigate the association between maternal HLA class II and
intrauterine growth retardation with associated birthweight of the newborn, in
women with preeclampsia. METHODOLOGY: Thirty preeclamptics and 30 normotensive
matched for age, parity and gestation were investigated for HLA class II profile
using Terasaki microlymphocytotoxicity test as the typing technique. The outcome
of the pregnancy in terms of intrauterine growth retardation, birthweight and
placental weight, were investigated to elucidate a susceptibility factor in the
HLA Class II profile of the preeclamptic women. RESULTS: HLA class II DR2, DR4,
DRw11, DRw14 and DQw2 were more common in the preeclamptic women (p < 0.04, 0.03,
0.05, 0.03, 0.05), while DQw3 was more common in the controls (p < 0.05). Mean
birthweight was 2.71 +/- 0.73 kg with preeclampsia compared to 3.4 +/- 0.4 kg for
controls (p < O.01). Low birthweight was 56.7% versus 6.1% (p < 0.001) and mean
placental weight was 474.8 +/- 100.8 gm versus 692.1 +/- 107.3 gm (p < 0.01). DR4
and DQW2 were significantly associated with intrauterine growth retardation with
associated low birthweight and placental weight (p < 0.01). CONCLUSION: HLA class
II hyaplotypes DR4, and DQw2 are associated with intrauterine growth retardation
with associated low birthweight and placental weight through preeclampsia. The
association between intrauterine growth retardation and HLA may be a direct
susceptibility factor. This needs further elucidation.
PMID- 9651658
TI - Prognostic relevance of immunohistology, tumor size and vascular space
involvement in axillary node negative breast cancer.
AB - OBJECTIVE: Adjuvant treatment for patients with axillary node negative (ANN)
breast cancer is controversial because operation alone gives a 70% cure rate.
Features which predict recurrence are needed and we therefore evaluated the
predictive value of tumor diameter and vascular involvement as well as of
estrogen receptors (ER), progesterone receptors (PR), p53, MIB-1, c-erb and PCNA
demonstrated by immunohistological staining in 178 patients with ANN breast
cancer. Although ER status, tumor diameter and vascular space involvement were
significantly correlated to the development of recurrence, their sensitivity,
specificity and predictive value were too low to give them clinical value.
PMID- 9651659
TI - Functional and phenotypic alterations in peritoneal macrophages from patients
with early and advanced endometriosis.
AB - The aim of this study was to elucidate whether peritoneal macrophage (pMO)
alterations are a generalized feature in all stages of endometriosis and the
effect of hormonal treatment on this leukocyte population. For this purpose we
quantified the number of pMO, the expression of HLA-DR antigen (pMO DR+),
percentages of pMO that reduced nitro-blue tetrazolium (pMO NBT+), and
interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by pMO from patients
with early (stages I/II) and advanced (stages III/IV) endometriosis, we also
analyzed some of these properties in pMO from patients which had been treated for
6 months with 800 mg/day of Danazol or gonadotropin releasing hormone agonist
(GnRHa). We found that there were a significant increase of the pMO number in
both types of patients, though the highest values were obtained in early
endometriosis (p < 0.001). Percentages of pMO DR+ were decreased in all patients
(p < 0.01) while percentages of pMO NBT+ were significantly increased. Production
of IL-1 by early and advanced endometriosis pMO were considerably enhanced. PGE2
release was not altered in early endometriosis pMO but, in advanced
endometriosis, pMO PGE2 levels were 100-fold higher than control values. In
posttreatment patients, the number of pMO and percentage of pMO NBT+ were similar
to early endometriosis patients, though the percentage of pMO DR+ was within the
normal range. We conclude that the pMO population, as well as IL-1 and PGE2
production, were altered in all stages of endometriosis, and that these changes
could be involved in the pathogenesis of endometriosis and associated
infertility. Hormonal treatments do not reverse the pMO changes.
PMID- 9651660
TI - Cancer associated serum antigen (CASA) levels in patients with breast carcinoma
and in 3 control groups without breast cancer.
AB - We have examined the predictive value of measurements of CASA (Cancer Associated
Serum Antigen) levels in patients with breast carcinoma. The measurement uses
monoclonal antibodies that bind to an epitope on the polymorphic epithelial
mucin. CASA levels were of less value compared with the levels of other tumor
markers (CA 15-3, CA 549 and CEA) in the management of patients with early breast
cancer.
PMID- 9651661
TI - Conjoined twin's cephalothoracopagus janiceps monoymmetros: a case report.
PMID- 9651662
TI - The sympathetic skin response in peripheral autonomic failure--evaluation in pure
failure, pure cholinergic dysautonomia and dopamine-beta-hydroxylase deficiency.
AB - The sympathetic skin response (SSR) detects changes in the electrical potential
in the skin in response to physiological and electrical stimuli and, therefore,
may indicate the integrity of sympathetic cholinergic neural pathways to sweat
glands. This has been evaluated in 21 patients with three forms of peripheral
autonomic failure. Of these, 15 had pure autonomic failure (PAF) without
additional neurological features; investigations indicated both sympathetic and
parasympathetic failure. Four patients had pure cholinergic dysautonomia (PCD),
with clinical and laboratory features indicating only cholinergic failure. Two
siblings had dopamine-beta-hydroxylase (DBH) deficiency with only sympathetic
adrenergic failure. None was on drugs affecting cholinergic function. Ten normal
individuals were aged-matched with PAF patients and studied as controls. The SSR
was recorded from the palmar hand and plantar foot surfaces, using previously
described techniques, in response to physiological (auditory, cough and
inspiratory gasp) and electrical stimuli. Nerve conduction studies excluded an
associated motor or sensory neuropathy. The SSR was present in all normal
individuals, and in both patients with DBH deficiency who had preserved
cholinergic and sudomotor function, It was absent in all 15 PAF and all four PCD
patients with impaired cholinergic function. Therefore, we conclude that the SSR
reflected sympathetic cholinergic function in these three different groups with
peripheral autonomic failure.
PMID- 9651663
TI - QTc interval, and autonomic and somatic nerve function in diabetic neuropathy.
AB - QTc intervals were measured using an electrocardiogram and other autonomic
function tests, in 66 neuropathy patients with non-insulin-dependent diabetes
mellitus (59.0 +/- 12.5 years; mean +/- SD). The change in R-R interval did not
influence the QTc interval, as calculated by the equation: QTc = QT + (1000 - R
R)/7 (ms), compared with the conventional Bazett's equation which appeared to
overcompensate in the case of a small R-R interval. The QTc interval in the
diabetic patients was significantly longer than that in age-matched controls. The
QTc interval showed an inverse correlation with the coefficient of variation of
the R-R interval and skin blood flow at rest. However, no correlation was found
between QTc interval and blood pressure change, change in heart rate on standing,
or results of the sympathetic skin response. The QTc interval did not correlate
significantly with motor or sensory nerve conduction parameters. We conclude that
the QTc interval can be a simple and useful autonomic indicator for diabetic
neuropathy relatively independent of other abnormalities of autonomic and somatic
nervous system function.
PMID- 9651664
TI - Heart rate variability effects of an agonist or antagonists of the beta
adrenoceptor assessed with scatterplot and sequence analysis.
AB - There is evidence that the processes regulating heart rate variations reflect non
linear complexity and show 'chaotic' determinism. Data analyses using non-linear
methods may therefore reveal patterns not apparent with conventional statistical
approaches. We have consequently investigated two non-linear methods, the
Poincare plot (scatterplot) and cardiac sequence (quadrant) analysis, and
compared these with standard time-domain summary statistics, during a normal
volunteer investigation of an agonist and antagonists of the cardiac beta
adrenoceptor. Under double-blind and randomized conditions (Latin square design),
12 normal volunteers received placebo, celiprolol (beta 1- and beta 2
adrenoceptor partial agonist), propranolol (beta 1- and beta 2-adrenoceptor
antagonist), atenolol (beta 1-adrenoceptor antagonist) and combinations of these
agents. Single oral doses of medication (at weekly intervals) were administered
at 22:30 hours with sleeping heart rates recorded overnight. The long (SDNN,
SDANN) and short-term (rmsSD) time-domain summary statistics were reduced by
celiprolol--effects different from the unchanged or small increases after
atenolol and propranolol alone. The Poincare plot was constructed by plotting
each RR interval against the preceding RR interval, but unlike previous
descriptions of the method, an automated computer method, with a high level of
reproducibility, was employed. Scatterplot length and area were reduced following
celiprolol and different from the small increases after propranolol and atenolol.
The geometric analysis of the scatterplots allowed width assessment (i.e.
dispersion) at fixed RR intervals. Differences between the drugs were confined to
the higher percentiles (i.e. 75% and 90% of scatterplot length: low heart rate).
The long-term time-domain statistics (SDNN, SDANN) correlated best with
scatterplot length and area whereas the short-term heart rate variability (HRV)
indices (rmsSD), pNN50) correlated strongly with scatterplot width. Cardiac
sequence analysis (differences between three adjacent beats; delta RR vs delta
RRn+1) assessed the short-term patterns of cardiac acceleration and deceleration,
four patterns are identified: +/+ (a lengthening sequencing), +/- or -/+
(balanced sequences), and finally -/- (a shortening sequence). A running count of
events by quadrant, together with the average magnitude of the differences was
computed. The beta-adrenoceptor partial agonist celiprolol increased acceleration
sequences. The duration of beat-to-beat difference shortened after celiprolol;
this contrasted with increased duration of beat-to-beat difference after
propranolol and atenolol. These results demonstrated a shift towards sympathetic
dominance after the beta-adrenoceptor partial agonist celiprolol contrasting in
parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and
atenolol. These non-linear methods appear to be valuable tools to investigate HRV
in health and in cardiovascular disease and to study the implications of
alterations in autonomic control during therapeutic intervention.
PMID- 9651666
TI - Effect of parasympathetic blockade on the signal-averaged electrocardiogram.
AB - Low parasympathetic activity is associated with late potentials detected at a
noise level of 0.4 microV in a signal-averaged electrocardiogram (SAECG)
following myocardial infarction. In contrast, at a noise level of 0.2 microV,
lowering parasympathetic activity influences late potential parameters in the
opposite direction in healthy subjects. The aim of this study was to estimate the
relationship between parasympathetic activity and the SAECG obtained at noise
levels of 0.4 and 0.2 microV in healthy subjects. Two SAECG recordings in 10
healthy subjects were obtained at noise levels of 0.2 and 0.4 microV before and
after parasympathetic blockade using atropine (1 mg). Signal-averaged QRS
duration (SA-QRS), late potential duration (LPD) defined as duration of terminal
signals below 40 microV, and root mean square voltage of the terminal 40 ms of
the averaged QRS (RMS40) were measured. At a noise level of 0.2 microV SA-QRS
reduced from 124 +/- 14 to 114 +/- 17 ms (P = 0.008), LPD from 37 +/- 10 to 28 +/
14 ms (P = 0.01), and RMS40 increased from 26 +/- 22 to 41 +/- 25 microV (P =
0.006) during parasympathetic blockade compared to baseline values. At a noise
level of 0.4 microV the SA-QRS (115 +/- 15 ms) and LPD (29 +/- 11 ms) were lower
and the RMS40 (37 +/- 23 microV) was higher compared to the noise level 0.2
microV, and no systematic alterations of the three variables were found during
parasympathetic blockade. The parasympathetic nervous system may induce a very
low-amplitude late potential in the SAECG. The data suggest that parasympathetic
activity and a low noise level may lead to a false late potential-positive SAECG
in low arrhythmia risk subjects. Therefore, we recommend the use of a noise level
of 0.4 microV or identification of high arrhythmia risk patients by late
potential and low parasympathetic activity.
PMID- 9651665
TI - Effect of a 'vagomimetic' atropine dose on canine cardiac vagal tone and
susceptibility to sudden cardiac death.
AB - We manipulated the level of cardiac vagal tone in dogs with healed myocardial
infarctions during exercise plus acute ischemia, to explore vagal involvement in
the pathophysiology of sudden cardiac death. We occluded the circumflex coronary
artery during the last minute of treadmill exercise in 32 dogs with healed
anterior myocardial infarctions. Twenty-one dogs experienced ventricular
fibrillation (susceptible) and 11 did not (resistant). On a subsequent day, we
gave intravenous low-dose atropine to susceptible dogs to increase their levels
of cardiac vagal tone, as estimated by moving polynomial time-series analysis of
R-R interval variability (0.24-1.04 Hz). We also measured vagal responses to
coronary occlusion at rest, before and after low-dose atropine. In susceptible
dogs, atropine increased the average vagal tone index at rest (atropine: 7.3 +/-
0.4 versus control: 6.6 +/- 0.5 ln ms2, P < 0.01) and during maximum exercise
(atropine: 2.5 +/- 0.4 versus control: 1.6 +/- 0.3 ln ms2, P < 0.01), but failed
to prevent ventricular fibrillation actually decreased from 63 +/- 3 to 42 +/- 2s
(P < 0.01), and R-R interval shortening elicited by coronary occlusion increased
(atropine: delta -144 +/- 64 versus control: delta -55 +/- 32 ms, P < 0.01). In
resting susceptible dogs, atropine significantly increased preocclusion indexes
of vagal tone (atropine: 7.8 +/- 0.3 versus control: 6.9 +/- 0.4 ln ms2, P <
0.01), but did not prevent large reductions of vagal tone during ischemia
(atropine: delta -4.4 +/- 0.6 versus control: delta -3.8 +/- 0.4 ln ms2, P >
0.05). We conclude that increases of resting vagal tone after low-dose atropine
in dogs with healed anterior myocardial infarctions do not protect against sudden
cardiac death. Quite the contrary, vagal tone is withdrawn more completely during
ischemia, and the time to ventricular fibrillation during exercise plus ischemia
is shortened.
PMID- 9651667
TI - Distribution of cardiovascular related cells within the human thalamus.
AB - Representation of cardiovascular function has not been investigated in the human
thalamus. In the rat, the insular cortex is the principal forebrain site of
cardiovascular representation whose afferents originate from a circumscribed
thalamic area (nucleus ventralis posterolateralis-parvicellular portion, VPLpc).
We therefore evaluated 4481 thalamic cells for phasic cardiovascular activity
using extracellular recording techniques in 60 unanesthetized patients undergoing
neurosurgical procedures. We identified 26 cells with phasic activity strongly
related to the cardiac cycle in 10 patients. These cells clustered within the
ventrocaudal nucleus of the thalamus (the principal sensory nucleus analogous to
the ventral posterior thalamic group in the rat and monkey) and were equally
distributed between the right and left sides. The majority of these cells (17/26)
showed peaks of phasic neuronal activity within 50 ms of the peak systolic
pressure; 35% had peripheral cutaneous fields in areas to which cardiac pain is
often referred. We suggest that these cells may be involved in the integration of
afferent baroreceptor information; may possibly be concerned with the generation
and/or processing of central cardiac pain in humans; and that their derangement
may possibly contribute to the lethal cardiovascular disturbances which occur in
fatal familial insomnia.
PMID- 9651668
TI - Short-term variability of blood pressure and heart rate in hyperthyroidism.
AB - The effect of hyperthyroidism on the short-term memory variability of blood
pressure and heart rate was evaluated in 12 untreated hyperthyroid patients
during thyrotoxicosis and after a 6 1/2 month treatment designed to achieve a
stable euthyroid state. Beat-by-beat finger blood pressure was measured with a
Finapres device. The pulse interval, from which pulse rate was derived, was
obtained from the blood pressure signal. Due to the significant change in heart
rhythm associated with thyrotoxicosis, both pulse interval (taken as a surrogate
of heart period) and pulse rate (taken as a surrogate of heart rate) were
computed. Power spectral analysis showed a reduction in the overall heart period
variability in the supine position in the hyperthyroid compared to the euthyroid
state. This effect was observed in the low-frequency (0.005-0.068 Hz), mid
frequency (0.068-0.127 Hz) and high-frequency (respiratory) domains as well, with
a significant reduction of the modulus of these bands of 31%, 35% and 47%,
respectively. The heart rate spectral modulus also exhibited a reduction of the
high-frequency component (31%) in the supine position in the hyperthyroid
subjects. These changes in heart rhythmicity corroborate a vagal deficit in
hyperthyroidism. In addition, blood pressure spectral power exhibited a
significant deficit in the orthostatism-induced mid-frequency systolic blood
pressure rise in the hyperthyroid state (64%) compared with the euthyroid state.
This observation may reflect a reduced vascular sympathetic activation with
standing. The resulting vasodilatation could well contribute to normalize blood
pressure in thyrotoxicosis in which cardiac output is increased.
PMID- 9651669
TI - Bacterial chemotaxis: unsolved mystery of the flagellar switch.
AB - Impressive progress has been made in understanding the mechanism of bacterial
chemotaxis and function of the flagellar motor, but how the direction of rotation
is reversed by the 'flagellar switch'--a central step in chemotaxis--remains
obscure and calls for new experimental approaches.
PMID- 9651670
TI - Transcriptional control: Tat cofactors and transcriptional elongation.
AB - HIV-1 gene expression requires the transactivator Tat, which stimulates viral
transcript elongation. Recent results show that two cellular cyclin-dependent
kinases, which phosphorylate the carboxy-terminal domain of the RNA polymerase II
large subunit, contact Tat and contribute to the control of transcriptional
elongation.
PMID- 9651671
TI - Ion channels: a first view of K+ channels in atomic glory.
AB - Crystal structures have been solved for the transbilayer pore domain of a
bacterial K+ channel and the tetramerisation domain of voltage-gated K+ channel.
These provide our first real structural insights into possible mechanisms of ion
selectivity and permeation for K+ channels.
PMID- 9651672
TI - Proteasome assembly: biting the hand.
AB - Proteasome assembly is regulated to ensure the enzyme is inactive until its
active sites are compartmentalized within an interior aqueous chamber. In yeast,
this depends on a dedicated chaperone that is trapped within the nascent
proteasome, and degraded on maturation of the proteolytic subunits.
PMID- 9651673
TI - Cell-mediated immunity: the role of bacterial protein secretion.
PMID- 9651674
TI - Meiosis: step-by-step through sporulation.
AB - A transcription factor, Ndt80p, has been identified that has a critical role in
the pathway that controls meiosis--sporulation--in budding yeast. Ndt80p
coordinately controls genes that mediate spore formation and progression through
the two meiotic divisions; it may also be a target of a checkpoint control.
PMID- 9651675
TI - Molecular chaperones: clamps for the Clps?
AB - The Clp/Hsp100 molecular chaperones are unusual in their ability to tease apart
protein aggregates and complexes. Recent results make a good case that these
chaperones bind substrates via PDZ-like domains; this may reflect a general
strategy for manipulating the] assembly state of substrate proteins.
PMID- 9651676
TI - Protein folding: a missing redox link in the endoplasmic reticulum.
AB - Native disulphide-bond formation during protein folding in the endoplasmic
reticulum requires oxidative machinery, the components and mechanism of which are
not yet fully understood. Two recent papers have identified a novel protein
component that appears to play a key role in this important redox pathway.
PMID- 9651677
TI - The pleckstrin homology domain of oxysterol-binding protein recognises a
determinant specific to Golgi membranes.
AB - BACKGROUND: Peripheral membrane proteins are targeted to the cytoplasmic face of
specific intracellular membranes. The organelle-specific ligands recognised by
peripheral proteins include other proteins and lipids. Oxysterol-binding protein
(OSBP) translocates from the cytoplasm to the Golgi apparatus on binding
oxygenated derivatives of cholesterol. The mechanism by which OSBP recognises the
Golgi is unknown. It does, however, contain a pleckstrin homology (PH) domain,
which in other proteins has been found to mediate regulated membrane binding,
although in all previously studied examples the binding is to the plasma
membrane. RESULTS: The PH domain of OSBP and of a yeast homologue, Osh1p, were
sufficient to target proteins specifically to mammalian Golgi membranes. In
addition, high level expression disrupted Golgi architecture and prevented
forward traffic of cargo protein. In vitro, the OSBP PH domain bound to Golgi
membranes in a manner apparently dependent on phosphatidylinositol-4,5
bisphosphate (PI(4,5)P2) or a related phosphatidylinositide. The OSBP PH domain
bound to PI(4,5)P2 in liposomes with a submicromolar dissociation constant.
CONCLUSIONS: The PH domains of OSBP and its yeast homologue recognise a
determinant which is specific to Golgi membranes and important for Golgi
function. The determinant appears to be a combination or a phosphatidylinositol
polyphosphate and a second, Golgi-specific feature.
PMID- 9651678
TI - Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian
nerve terminals.
AB - BACKGROUND: Following exocytosis at the synapse, synaptic vesicle components are
recovered by endocytosis. Morphological analysis has suggested that this occurs
by a clathrin-mediated pathway, and the GTPase dynamin is thought to be involved
in 'pinching off' endocytosing vesicles. The finding that the calcium-dependent
phosphatase calcineurin can dephosphorylate dynamin and two other proteins
implicated in endocytosis (amphiphysin and synaptojanin) has suggested a
potential role for calcium and dephosphorylation in regulating synaptic vesicle
endocytosis. RESULTS: We tested this hypothesis with an endocytosis assay in
isolated nerve terminals (synaptosomes) that relies on the use of the fluorescent
dye FM2-10. In synaptosomes, vesicle recycling occurs predominantly via a pathway
dependent on both dynamin and amphiphysin. We found that endocytosis could be
stimulated maximally at calcium concentrations that yielded only low levels of
exocytosis, suggesting that the two processes had different calcium sensitivities
cyclosporin A and Fk506, we identified calcineurin as a calcium sensor for
endocytosis and showed that its activity is essential for synaptic vesicle
endocytosis in synaptosomes. CONCLUSIONS: Our results suggest that dynamin
dependent synaptic vesicle endocytosis is triggered by calcium influx occurring
upon nerve-terminal depolarisation. An essential mediator of calcium's effect is
calcineurin, the activation of which leads to dephosphorylation of at least four
proteins implicated in endocytosis-dynamin, amphiphysin 1, amphiphysin 2 and
synaptojanin. Our findings also imply that endocytosis and exocytosis may occur
in tandem in vivo simply because they share a responsiveness to calcium influx,
rather than because they are mechanistically coupled.
PMID- 9651679
TI - The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and
Cdc27 during S phase and early mitosis.
AB - BACKGROUND: In eukaryotic cells, a specialized proteolysis machinery that targets
proteins containing destruction-box sequences for degradation and that uses a
ubiquitin ligase known as the anaphase-promoting complex/cyclosome (APC) plays a
key role in the regulation of mitosis. APC-dependent proteolysis triggers the
separation of sister chromatids at the metaphase-anaphase transition and the
destruction of mitotic cyclins at the end of mitosis. Recently, two highly
conserved WD40-repeat proteins, Cdc20 and Cdh1/Hct1, have been identified as
substrate-specific regulators for APC-dependent proteolysis in the budding yeast
Saccharomyces cerevisiae. Here, we have investigated the cell cycle regulation of
Cdc20 and Cdh1/Hct1. RESULTS: Whereas the levels CDH1/HCT1 RNA and Cdh1/Hct1
protein are constant throughout the cell cycle, CDC20 RNA and Cdc20 protein are
present only during late S phase and mitosis and Cdc20 protein is unstable
throughout the entire cell cycle. The instability of Cdc20 depends on CDC23 and
CDC27, which encode components of the APC. During the G1 phase, a destruction box
within Cdc20 mediates its instability, but during S phase and mitosis, although
Cdc20 destruction is still dependent on CDC23 and CDC27, it does not depend on
the Cdc20 destruction box. CONCLUSIONS: There are remarkable differences in the
regulation of Cdc20 and Cdh1/Hct1. Furthermore, the APC activator Cdc20 is itself
a substrate of the Cdc27 have a role in the degradation of Cdc20 during S Phase
and early mitosis that is not mediated by its destruction box.
PMID- 9651680
TI - Probing the role of homomeric and heteromeric receptor interactions in TGF-beta
signaling using small molecule dimerizers.
AB - BACKGROUND: Transforming growth factor Beta (TGF-Beta) arrests many cell types in
the G1 phase of the cell and upregulates plasminogen activator inhibitor 1 (PAI
1). The type 1 (TGF-Beta RI) an II (TGF-Beta RII) TGF-Beta receptors mediate
these and other effects of TGF-Beta on target cells. TGF-Beta initially binds to
TGF-Beta RII and subsequently TGF-Beta RI is recruited to form a heteromeric
complex. TGF-Beta RI phosphorylates the downstream effectors Smad2 and Smad3,
leading to their translocation into the nucleus. Here, we explored the role of
receptor oligomerization in TGF-Beta signaling. RESULTS: We constructed fusion
proteins containing receptor cytoplasmic tails linked to binding domains for
small-molecule dimerizers. In COS-1 cells, recruitment of a soluble TGF-Beta RII
tail to a myristoylated TGF-Beta RI tail promoted Smad2 nuclear translocation. In
mink lung cells, homo-oligomerization of a myristoylated TGF-Beta Ri tail in
presence of a myristoylated TGF-Beta RII tail activated the PAI-1 promoter.
Oligomerization of an acidic mutant of the TGF-Beta RI tail in absence of TGF
Beta RII activated the PAI-A promoter and inhibited the growth of mink lung
cells. CONCLUSIONS: Non-toxic, small molecules designed to oligomerize
cytoplasmic tails of TGF-Beta receptors at the plasma membrane can activate TGF
Beta signaling. Although TGF-Beta normally signals through two receptors that are
both necessary for signaling, in one small-molecule system, a dimerizer activates
signaling through a single type of receptor that is sufficient to induce TGF-Beta
signaling. These methods of activating TGF-Beta signaling could be extended to
signaling pathways of other TGF-Beta superfamily members such as activin and the
bone morphogenetic proteins.
PMID- 9651681
TI - Indirect evidence for Delta-dependent intracellular processing of notch in
Drosophila embryos.
AB - Cell-cell signaling mediated by the receptor Notch regulates the differentiation
of a wide variety of cell types in invertebrate and vertebrate species, but the
mechanism of signal transduction following receptor activation is unknown. A
recent model proposes that ligand binding induces intracellular processing of
Notch; the processed intracellular form of Notch then translocates to the nucleus
and interacts with DNA-bound Suppressor of Hairless (Su(H)), a transcription
factor required for target gene expression. As intracellular processing of
endogenous Notch has so far escaped immunodetection, we devised a sensitive
nuclear-activity assay to monitor indirectly the processing of an engineered
Notch in vivo. First, we show that the intracellular domain of Notch, fused to
the DNA-binding domain of Gal4, regulated transcription, in a delta-independent
manner. Second, we show that full-length Notch, containing the Gal4 DNA-binding
domain inserted 27 amino acids carboxy-terminal to the transmembrane domain,
activated transcription in a delta-dependent manner. These results provide
indirect evidence for a ligand-dependent intracellular processing event in vivo,
supporting the view that Su(H)-dependent Notch signaling involves intracellular
cleavage, and transcriptional regulation by processed Notch.
PMID- 9651682
TI - The Pristionchus pacificus mab-5 gene is involved in the regulation of ventral
epidermal cell fates.
AB - One system that can be used to study the evolution of gene function is the
nematode vulva. In Caenorhabditis elegans, the vulva is formed from three of the
six multipotent precursors P(3-8).p. Comparison of vulval development between C.
elegans and Pristionchus pacificus has revealed that, during evolution, there
have been changes in the specification of cell fate for certain vulval cells. For
example, the cell P8.p is a vulval precursor cell (VPC) in C. elegans, but is
incompetent to adopt vulval fate in P. pacificus We have fate specification and
have isolated P. pacificus mutants with a second vulva-like structure in the
posterior region resulting from the ectopic differentiation of P8.p Genetic and
molecular analysis indicated that point mutations in the Hox-cluster gene mab-5
of P. pacificus cause this multivulval phenotype. Further cell ablation studies
revealed that the differentiation of P8.p is independent of gonadal signaling. In
C. elegans, mab-5 also acts in P8.p specification, but mab-5 mutant animals do
not develop differs between species, indicating that alterations in the intrinsic
properties of P8.p and corresponding changes in the functional specificity of mab
5 have occurred during evolution.
PMID- 9651684
TI - Conversion of zebrafish blastomeres to an endodermal fate by TGF-beta-related
signaling.
AB - The endoderm contributes cells to the gut, and participates in the induction and
patterning of the vertebrate head and heart. The mechanisms controlling the
formation of endoderm are poorly understood. Commitment of endoderm cells occurs
at the onset of gastrulation and requires cell interactions; studies in vitro
have implicated transforming growth factor Beta (TGF-beta)-related molecules in
this process. TARAM-A is a zebrafish receptor kinase that is related to the type
I subunit of the TGF-beta receptor, and is expressed in presumptive
endomesodermal cells at gastrulation. We provide here evidence for its
involvement in endoderm formation in vivo. Activation of TARAM-A was found to
drive blastomeres towards an endodermal fate. The induced endoderm behaved ad
endogenous endoderm during gastrulation: it migrated in contact with the yolk and
expressed endoderm-specific markers. Loss-of-function mutations in the zebrafish
one-eyed-pinhead (OEP) gene lead to defects in heart formation, defects of the
ventral central nervous system (CNS) and cyclopia. Mutant embryos also lack
endoderm and anterior mesoderm. Endoderm formation in oep mutant embryos was
found to be restored by the activation of the TARAM-A signaling pathway. Cardiac
and ocular defects, but not midline CNS structures, were rescued non
autonomously, demonstrating that endoderm may provide signals that can pattern
the eye anlage, and which are distinct form those specifying the ventral midline
of the CNS.
PMID- 9651683
TI - The kit receptor promotes cell survival via activation of PI 3-kinase and
subsequent Akt-mediated phosphorylation of Bad on Ser136.
AB - The c-kit-encoded receptor protein tyrosine kinase for stem cell factor (Kit/SCF
R) is essential for the development of cells within the hematopoietic,
melanogenic and gametogenic lineages. SCF stimulation induces activation of
phosphatidylinositol (PI) 3-kinase, which is required for SCF-induced mitogenesis
and cell survival, and for activation of the serine/threonine, we found that, in
response to SCF Akt became activated and mediated phosphorylation of Bad, a pro
apoptotic molecule, in a PI-3-kinase-dependent manner. Phosphorylation of Bad was
restricted to Ser112 and Ser136 in vivo, but only the Akt phosphorylation sit
Ser136 was essential for SCF-promoted cell survival. Furthermore, Bad and Akt
interacted and colocalized in intact cells. A Kit/SCF-R gain-of-function mutant
that has increased mitogenic and PI 3-kinase activation potential, due to the
absence of the two protein kinase C negative feedback phosphorylation site,
enhanced both Akt activation and Bad phosphorylation and also resulted in
increased cell survival. Such a mechanism may account for how deregulated PI 3
kinase activity and naturally occurring gain-of-function point mutants of Kit/SCF
R lead to cellular transformation and fatal malignancies in man.
PMID- 9651685
TI - Sif2p interacts with Sir4p amino-terminal domain and antagonizes telomeric
silencing in yeast.
AB - Several regions of the Saccharomyces cerevisiae genome are subject to position
dependent transcriptional repression mediated by a multi-component nucleosome
binding complex of silent information regulator proteins (Sir2p, Sir3p and
Sir4p). These proteins are present in limiting amounts in the nucleus and are
targeted to specific chromosomal regions by interaction with sequence-specific
DNA-binding factors. Different sites of repression compete for Sir complexes,
although it is not known how Sir distribution is regulated. In a screen for
factors that interact with Sir4p amino terminus, we have cloned SIF2, which
encodes a WD40-repeat-containing factor that disrupts telomeric silencing when
overexpressed. In contrast to deletion of SIR4, SIF2 deletion improved telomeric
repression, suggesting that under normal conditions Sif2p antagonizes Sir4p
function at telomeres. Sif2p overexpression altered the subnuclear localization
of Sir4p, but not its protein expression level, suggesting that Sif2p may recruit
Sir4p to nontelomeric sites or repression. The sif2 mutant strains were
hypersensitive to a range of stress conditions, but did not have decreased
viability and did not alter repression in the rDNA. In conclusion, Sif2p
resembles the Sir4p regulatory proteins Sir1p and Uth4p in that it competes for
the functional assembly of Sir4p at telomeres, yet unlike Sir1p or Uth4p, it does
not target Sir4p to either mating-type or rDNA loci.
PMID- 9651686
TI - Service development to meet the needs of 'people with communication disabilities'
in developing countries.
AB - PURPOSE: In spite of the catastrophic consequences of impaired communication
skills on the quality of human life, development of services for people with
communication disabilities have low priority in health care and rehabilitation.
Nowhere is this more apparent than in developing countries. The low coverage
levels of the limited services which do exist in these countries, indicate a need
to develop new and innovative service structures. It is to this end, given the
limited literature available, that this review looks mainly at articles of a
descriptive nature based on clinical experience. The review seeks to identify
ideology which could be used to under-pin alternative service delivery and
structures. METHOD: Three collections of literature relevant to the topic under
discussion are identified, one collection relates to impairment categories, one
to disability perspectives and one to speech and language therapy provision. It
is recognized that all three collections are needed to form a basis for
innovative change, but this review aims to examine the latter collection only,
referring the reader to items in the other collections, when relevant. RESULTS:
The information reviewed is analysed for recurring themes and the results are
seen to concur with many of the disability perspectives expressed in present day
literature.
PMID- 9651687
TI - Effects of a multidisciplinary rehabilitation programme on health-related quality
of life in patients with prolonged musculoskeletal disorders: a 6-month follow-up
of a prospective controlled study.
AB - PURPOSE: The aim of this prospective, controlled, follow-up study (6 months) was
to examine the effects of a multidisciplinary rehabilitation programme on
perceived health-related quality of life (HRQL) in patients with prolonged
musculoskeletal disorders (PMSD). The programme focused on body awareness therapy
and cognitive and relaxation treatment. METHOD: The rehabilitation group
comprised 122 patients, and there were 114 patients in the matched control group
(CG). Both groups of patients had access to primary health care. Baseline data
were compared with 6-month follow-up data within and between the groups. The
following measurements were employed: HRQL (Nottingham Health Profile), body
awareness, postural control, pain (VAS), pain-related medicine consumption,
isometric arm muscle endurance, aerobic capacity, psychosomatic symptoms,
physical and psychosocial working environment and sick leave. RESULTS: Variables
that improved significantly as compared with the CG were: HRQL, anxiety, pain
related to movements, psychosomatic symptoms and need for pain-related medicines.
CONCLUSIONS: The multidisciplinary rehabilitation programme used here improved
HRQL in patients with PMSD to a greater extent than the standard treatment
provided within primary heath care (p = 0.01) at least in the short term.
PMID- 9651688
TI - Hospital-based rehabilitative care versus outpatient services: effect on
functioning and health status.
AB - PURPOSE: The goal of this clinical trial was to examine the long-term impact of
rehabilitative care on the health status of patients diagnosed with a disabling
disorder. METHOD: Study patients consisted of first-time hospitalizations from
diagnostic groups commonly admitted for inpatient rehabilitation, including
nervous, circulatory, and musculoskeletal disorders or injury. Patients were
randomly assigned to inpatient rehabilitation (n = 43) or to outpatient follow-up
(n = 42) in which the usual medical services were provided but no scheduled
rehabilitative therapies were offered. Specific objectives of the study were to
determine the effects of impatient rehabilitation on: (1) functional ability, (2)
health and mental health status, (3) personal adjustment, and (4) family
function. Cost and use of health-care resources were descriptively assessed.
RESULTS: Analysis of covariance found no significant treatment effects, either at
6 months or at 1 year, for any of the variables under study. In addition, there
were no differences between groups in their use of nursing homes, length of
hospital stay, mortality, or in the number of hospital readmissions or clinic
visits during the first year after hospital discharge. Use of rehabilitation
services and cost of care was significantly higher than outpatient services. The
findings were consistent with previous studies for most outcomes, with the major
exception being functional improvements. Contrary to earlier studies,
rehabilitation was not found to effectively produce lasting functional outcomes.
However, study conditions may not have fully corresponded to those of previous
studies, and further research is needed. The patient sample was representative of
a full inpatient service and therefore more heterogeneous than samples reported
in prior studies, but the small sample size (due to reductions in the number of
admitted patients to the rehabilitation unit during the course of the study)
precluded subgroup analysis of diagnostic groupings. CONCLUSION: The findings
suggest that hospital-based rehabilitative care does not have lasting benefits,
and that alternative care or supportive follow-up by a subacute-care facility may
be needed to assist patients in maintaining functional gains and health benefits.
PMID- 9651689
TI - Percutaneous endoscopic gastrostomy in neurological rehabilitation: a report of
six cases.
AB - PURPOSE: This study reports the cases of six patients with severe chronic
neurological disability and swallowing difficulties due to traumatic brain injury
(TBI), anoxia and multiple sclerosis (MS). METHOD: The patients required
nutritional supplement through percutaneous endoscopic gastrostomy (PEG).
RESULTS: Their clinical follow-up showed a decrease of intercurrent medical
complications, especially pressure sores. In addition, an improvement of
oropharyngeal function was observed in some patients, also accompanied by
slightly better basic psychomotor functions such as vigilance, sustained
attention and tone or motor control. However, not every patient did improve with
this procedure. The two MS patients benefited most, while the improvement was
less homogenous in the three TBI patients. CONCLUSIONS: The advantages of PEG
over nasogastric tube on oropharyngeal function can be related to the absence of
pharyngeal irritation and its role in overall recovery could be due to an
increase in social activities, a control of infections, a better rehabilitation
schedule and a long-term effect on brain function due to better nutritional
support.
PMID- 9651690
TI - Re: Clinical commentary. Disability and rehabilitation.
PMID- 9651691
TI - Associated EMG responses to voluntary hand movement in probable Alzheimer's
disease.
AB - The goal of this work is to dilucidate the mechanism that yields the associated
EMG responses in patients with probable Alzheimer's disease. Seventeen subjects
fulfilling this criteria and ten normal subjects as a control group were
selected. They were asked to perform an oddball task in which they had to
discriminate between two kinds of stimuli and produce a response to one of them.
Results show that reaction times in controls and in patients when there is no
associated EMG are equal in latency. When the associated EMG response occurs in
the pathological group reaction time is significantly increased. Furthermore, the
associated EMG response is delayed in 55 milliseconds when compared to the
voluntary movement. Although these results may reflect some controversy, we
interpret this finding as a contralateral inhibitory deficit associated to the
corpus callosum abnormalities that occur in the evolving course of Alzheimer's
disease.
PMID- 9651692
TI - Visual evoked potentials in hypothyroidism: a long-term evaluation.
AB - Visual Evoked Potentials (VEP) were measured in 9 new-diagnosed hypothyroid
female patients--mean age 46 +/- 12 ys--before treatment, during (with monthly
evaluations) thyroid hormone replacement therapy and after long-term therapy, at
the achievement as well as one year after having achieved and maintained
euthyroidism. Three of the hypothyroids had abnormally prolonged latencies (m.v.
131.7 +/- 7.9 ms), while 7 had lower than normal amplitude (m.v. 2.3 +/- 2.8
microV). No remarkable change of amplitude was observed after the achievement of
euthyroidism, after a mean time of 5.9 +/- 4.9 months (range 2-14 months). A
significant shortening of latency (m 128.3 +/- 7.6 ms), even still higher than
the control value (m 122.7 +/- 3.7 ms) was found. Significant correlation between
P100 latency and thyroid hormone levels was found for TT4 (r = 0.3353; p =
0.005), TT3 (r = 0.2568; p = 0.032) and FT4 (r = 0.3572; p = 0.002). No further
improvement in P100 latency (m 129.5 +/- 7.2 ms; p = 0.037) was found one year
after the achievement of euthyroidism, while a remarkable amplitude increase (m
9.2 +/- 3.4 micro; p = 0.001) was observed. Our findings indicate that, as well
as other studied parameters, VEP are reversibly alterated in hypothyroidism,
probably in relation to metabolic rather than to structural alterations.
Moreover, VEP can represent a useful neurophysiologic parameter for quantitation
of SNC involvement in hypothyroidism.
PMID- 9651693
TI - Electrophysiological study of myoclonus in pediatric practice.
AB - Myoclonus can be caused from a variety of central nervous system disorders. With
regard to its pathophysiology, much work has been done in adult patients, but
reports from pediatric clinics are scarce. We describe the clinical and
electrophysiological features of four different types of myoclonus in children
using back averaging technique. In a patient with cortical reflex myoclonus,
myoclonic jerks were induced in the distal right arm by taps on the ipsilateral
fingers. Myoclonus was preceded by the cortical spike which was localized
posterior to the central sulcus contralateral to the myoclonus, and the cortical
spike was time-locked to the myoclonus. In a patient with subcortico-cortical
myoclonus, myoclonus occurred as a focal motor seizure. Myoclonic jerks were
preceded by generalized cortical waves which were of maximal amplitude over the
cortex contralateral to the myoclonus, and cortical waves time-locked to the
myoclonus. A patient with spinal myoclonus had rhythmical and segmental
myoclonus. Myoclonus was induced in both arms after electrical stimulation at the
wrist with a latency which was slightly longer than that of the F wave. In a
patient with brainstem myoclonus, muscle activity was bilaterally synchronous and
was predominant in the proximal flexors. The pattern of muscle recruitment
suggested that the myoclonus signal travelled downward along the spinal cord and
upward through the brainstem. The back averaging technique is essential in the
differential diagnosis of myoclonus.
PMID- 9651694
TI - Electromyographic evaluation of the rectus femoris muscle during exercises
performed on the leg press.
AB - The rectus femoris was analysed in 10 volunteers during knee flexion and
extension with the feet in normal, plantar flexion and dorsal flexion positions.
Hewlett-Packard surface electrodes, an electromyographic signal amplifier, a
computer equipped with an A/D conversion plaque (Model CAD 10/26), software
specially designed to record and analyse the signals, Horizontal Leg Press, and
electrogoniometers were used. The rectus femoris muscle showed strong potentials
at the beginning of knee extension. In the simultaneous bending of the knee and
hip the activity was strong toward the end of the movement. The rectus femoris
showed a similar activity both in the upper and lower platforms. As for foot
positions, the rectus femoris showed the smallest potentials with the foot in
plantar flexion and the largest ones with the foot in dorsal flexion.
PMID- 9651695
TI - Effect of nerve block on sural amplitude during remote muscle contraction.
AB - We previously reported that the median sensory nerve action potentials (SNAPs)
increased in amplitude during both near (3) and remote (4) muscle contraction.
The objective of the present project was to begin to study the pathway by which
this occurred. The sural amplitude was measured after one min. of isometric
biceps contraction and compared pre and post lidocaine nerve block in 10 healthy
subjects. The baseline was defined as the least amount of current needed to
elicit a minimal sural response pre contraction. This level of stimulus remained
constant throughout the experiment. Results showed that the sural amplitude
peaked 4 min. after muscle contraction. An 8.1 microV increase in sural amplitude
from baseline was noted pre injection as 5 min. post contraction, and an increase
of 13.4 microV was noted comparing pre to post injection amplitudes at the same
time. Statistical analysis using two-way interaction comparing the time courses
pre and post injection showed a 92% chance the responses were dissimilar Post hoc
least significant difference (LSD) analyses were significant at 4 min. (p = .005)
and 6 min. (p = 0.29) post contraction. In conclusion, the increase in sural
amplitude after remote muscle contraction was no longer apparent after proximal
sural nerve block. This suggests that the nerve itself is required in the final
common pathway for the transmission of this induced signal.
PMID- 9651696
TI - Quantitative study of Stewart-Holmes test.
AB - Stewart-Homes test (SHT) is an ordinary neurological test performed for the
diagnosis for cerebellar disease. We developed a quantitative method based on SHT
carried out on the upper limb. Nineteen cerebellar patients and fifteen volunteer
healthy subjects were tested. During the test, acceleration of forearm and two
associated surface EMGs over biceps and triceps brachialis were recorded and
analyzed. (1) Acceleration curve showed an oscillating pattern with flexion and
extension over the elbow in both groups, but in cerebellar patient group, the
acceleration oscillation wave was more pronounced and latencies of peak
acceleration were significantly longer. (2) Correspondingly, the EMGs timing
parameters were also different between the two groups: in patient group, ceasing
isometric biceps contraction was delayed; rebound EMGs bursts over both biceps
and triceps were prolonged. (3) Modelization of the oscillation of acceleration
curve with dampened oscillation model showed that in patient group the
oscillating amplitude attenuated much more slowly than in control group. A
standard curve was established for detecting the acceleration profile
abnormalities of SHT in cerebellar patients.
PMID- 9651697
TI - Event-related potentials in the segmental exclusion syndrome of the upper limb.
AB - Upper limb segmental exclusion syndromes are frequent after traumatic or
infectious affections. They can be defined as an insufficient utilization of a
limb segment--fingers or hand--reversible on verbal exhortation and arising in
subjects with no other neurologic or psychiatric disorder. Our hypothesis was
that the segmental exclusion syndrome could be likened to a neglect behavior. To
verify the validity of this hypothesis, we measured digital nerve short-latency
SEP and SEP-P300 waves in response to odd-ball task target stimuli in healthy
volunteers (n = 11) and patients with digit exclusion syndromes (n = 19). For N20
latency, there was no significant difference (Wilcoxon's test: p = 0.52) between
normal and excluded digits. Stimulation of the excluded vs normal digit resulted
in a significant lengthening in SEP-P300 latency (p = 0.0003). The implication of
these results and means of extending our knowledge of the pathophysiology of
exclusion syndromes are discussed.
PMID- 9651698
TI - The abductor pollicis brevis R1 response: normative data and physiological
behavior.
AB - BACKGROUND: Although H reflexes cannot be reliably recorded from resting human
hand intrinsic muscles, a short latency R1 response, thought to be similar to the
H reflex, is readily obtained from upper extremity muscles during voluntary
contraction. METHODS: The right and left median nerves of 20 normal subjects were
repetitively stimulated at 3 Hz at stimulus intensities corresponding to
threshold and 20%, 40% and 60% of maximal M response, recording from the abductor
pollicis brevis muscle. Studies were done during both minimal and moderate
voluntary contraction. RESULTS: The R1 response was present in all subjects at
the 40% stimulation intensity level during moderate contraction. The mean latency
was 27 ms (SD 1.77 ms) with a good correlation to arm length. The mean amplitude
was 1.17 mV (SD 0.79 mV). CONCLUSIONS: Abductor pollicis muscle R1 response can
be reliably measured, although latency showed much less intersubject and side to
side variability than amplitude. This technique may be useful for the assessment
of demyelinative lesions of the inferior segments of the brachial plexus and C8
T1 roots.
PMID- 9651699
TI - Low molecular weight heparins in acute coronary syndromes.
PMID- 9651700
TI - Sleep apnoea: a therapeutic target in congestive heart failure.
PMID- 9651701
TI - Time delays in starting thrombolytic therapy.
PMID- 9651702
TI - Trans-septal catheterization: a new frontier in clinical electrophysiology?
PMID- 9651703
TI - Evaluation of chest pain in women.
PMID- 9651704
TI - Cardiothoracic ratio and relative heart volume as predictors of coronary heart
disease mortality.
PMID- 9651705
TI - Pushing the ablation frontier in atrioventricular node reentrant tachycardia.
PMID- 9651706
TI - Overview of studies of exercise training in chronic heart failure: the need for a
prospective randomized multicentre European trial.
PMID- 9651707
TI - Should we screen for asymptomatic left ventricular dysfunction to prevent heart
failure?
AB - A programme to detect and treat asymptomatic left ventricular dysfunction would
seem to fulfil all five principles of screening. Indeed, such a programme would
appear to be at least as firmly based as those already in existence for, for
example, cervical and breast cancer. Further evaluation of the screening of high
risk groups to detect asymptomatic left ventricular systolic dysfunction with the
aim of giving treatment to prevent the development of heart failure is merited.
PMID- 9651708
TI - Assessment of tissue viability: clinical demand and problems.
PMID- 9651709
TI - Cardiothoracic ratio and relative heart volume as predictors of coronary heart
disease mortality. The Whitehall study 25 year follow-up.
AB - AIM: To examine the association of radiographic measures of heart size with
mortality from coronary heart disease. METHODS AND RESULTS: One thousand, one
hundred and ninety-one male civil servants aged 40-69 years were followed-up for
mortality over 25 years in relation to cardiothoracic ratio and relative heart
volume. A high cardiothoracic ratio and relative heart volume predicted coronary
(n = 196 deaths) and all-cause mortality, but not respiratory or malignant
mortality. After adjustment for age, systolic and diastolic blood pressure, the
highest (> or = 0.47) compared to the lowest quintile of the cardiothoracic ratio
(< 0.40) was associated with a rate ratio of 1.84 (95% CI 1.14-2.97) for the
effect on coronary heart disease mortality. Further adjustment for heart rate,
smoking, cholesterol, angina and ECG ischaemia had little effect, reducing the
rate ratio to 1.65 (95% CI 1.01-2.70). Similar rate ratios were observed for
relative heart volume. CONCLUSIONS: Cardiothoracic ratio within the range
considered 'normal' in clinical practice predicted coronary heart disease
mortality independent of established coronary heart disease risk factors. The
relative heart volume, which uses measurements from the lateral as well as the
posteroanterior chest X-ray, did not predict coronary heart disease any better
than the cardiothoracic ratio. The extent to which left ventricular mass and
systolic dysfunction-- pathophysiological correlates of the cardiothoracic ratio
and relative heart volume--are independent risk factors for coronary heart
disease should be further investigated.
PMID- 9651710
TI - Lesion morphology assessed by pre-interventional intravascular ultrasound does
not predict the incidence of severe coronary artery dissections.
AB - AIMS: Coronary artery dissections are common findings following percutaneous
transluminal coronary angioplasty and occur with an incidence of approximately
20% to 40%. The purpose of this study was to evaluate the impact of intravascular
ultrasound for the prediction of severe dissections by pre-interventional
analysis of lesion morphology and plaque composition. METHODS AND RESULTS: Pre-
and post-interventional intravascular ultrasound was performed in 197 patients
with 205 lesions. Using intravascular ultrasound criteria, 24 lesions were
classified as soft (hypo- or iso-echogenic), 73 as intermediate (hyper-echogenic)
and 108 as calcified (calcific arc > 90 degree of the vessel circumference).
Additionally, calcium localization was defined as subendothelial, central or
deep. The incidence of dissections was 37.5% in patients with soft lesions, 24.7%
in patients with intermediate and 36.1% in patients with calcified lesions. In
calcified lesions, the occurrence of severe dissections was not dependent on the
localization of calcium deposits. The procedural parameters were similar in all
patients. The minimal inflation pressure, however, was significantly higher in
calcified lesions (P < 0.01). CONCLUSION: Assessment of lesion morphology by
intravascular ultrasound cannot predict the occurrence of severe dissections
following percutaneous transluminal coronary angioplasty. Furthermore, despite
significantly higher inflation pressures in heavily calcified lesions, the
incidence of dissections was found to be comparable in all lesions.
PMID- 9651712
TI - Delays in thrombolytic therapy for acute myocardial infarction in Finland.
Results of a national thrombolytic therapy delay study. Finnish Hospitals'
Thrombolysis Survey Group.
AB - OBJECTIVE: To determine lengths and causes of pre- and in-hospital delays in
thrombolytic treatment. DESIGN: A prospective national survey covering 48 of the
51 Finnish university, central and general hospitals to obtain basic data before
the start of a public campaign to shorten patient-related delay in acute
myocardial infarction. SUBJECTS: One thousand and twelve consecutive patients
with acute myocardial infarction who received thrombolytic therapy over 3 months
in 1995 and who represent 40% of all patients with confirmed acute myocardial
infarction. RESULTS: The median interval between onset of infarction symptoms and
initiation of thrombolytic therapy was 160 min (30-647). Only 13% of the patients
received thrombolysis within 60 min and 38% within 120 min. The median time from
the onset of symptoms to the call for help was 60 min (5-491), and no difference
was found in patients with or without a history of previous myocardial infarction
(60 and 64 min, respectively). Only 52% of the patients called to the dispatch
centre. The median delay from calling for help to hospital arrival was 40 min (10
170). The median in-hospital door-to-needle thrombolysis delay was 40 min (12
196). In 13% of hospitals the median delay was more than 60 min. The emergency
physician encountered difficulties in decision making in 33% of cases.
CONCLUSIONS: Only 38% of the patient received thrombolysis within 2 h of onset of
symptoms. Patient-related delay before they sought help accounted for the major
portion of the total treatment delay. Thus the findings emphasize the importance
of prompt action when people are confronted with an acute heart attack.
Reorganizing the emergency medical service and emergency department routines is
also a necessary target to shorten thrombolysis delays. The delay attributable to
transporting patients could be shortened by initiating thrombolytic treatment in
the pre-hospital setting. In Finnish hospitals, door-to-needle delay was
acceptable in cases with clear indications for thrombolysis. However, emergency
physicians often had diagnostic difficulties, which led to remarkably longer in
hospital delays.
PMID- 9651711
TI - The 60 Minutes Myocardial Infarction Project. Characteristics on admission and
clinical outcome in patients with reinfarction compared to patients with a first
infarction.
AB - PURPOSE: The purpose of the study was to evaluate parameters that characterize
patients with myocardial reinfarction as compared to patients with a first
infarction in clinical practice, and possibly to determine their clinical
outcome. METHODS: The 60 minutes Myocardial Project is a German multicentre
prospective observational study in which 136 hospitals are participating.
Fourteen thousand, nine hundred and eighty consecutive patients with acute Q wave
myocardial infarction were included from July 1992 to September 1994. RESULTS:
Out of these 14,980 patients, there were 2854 (19%) with reinfarction and 12,126
(81%) with a first infarction. Patients with a reinfarction arrived at the
hospital 24 min earlier than patients with a first infarction (pre-hospital delay
156 vs 180 min; P < 0.001); the door-to-needle time with reinfarction was longer
(38 vs 30 min; P < 0.001); however, patients with reinfarction were older (69 vs
66 years; P < 0.001), had a lower rate of a diagnostic first ECG (54 vs 71%; P <
0.001) and received thrombolytic therapy less frequently than patients with a
first infarction (46 vs 52%; P < 0.001). A low number of patients received
primary PTCA ( n = 205) since only a few hospitals offered a primary PTCA service
at the time the study was performed. In patients with reinfarction, there were
more reasons as to why thrombolytic therapy was not given (24 vs 21%; P < 0.001).
Left bundle branch block occurred more frequently in patients with reinfarction
(15 vs 8%; P < 0.001). The intra-hospital course in patients with reinfarction
was associated with an increase of complications and intra-hospital death (23 vs
15%; P < 0.001. CONCLUSIONS: Although reinfarction patients arrived earlier at
hospital than patients with a first infarction, the former received thrombolytic
therapy less frequently than the latter. Patients with reinfarction were older,
more frequently had a non-diagnostic ECG on admission and had a higher rate of
contraindications against thrombolytic therapy.
PMID- 9651713
TI - Frequency and prognostic implications of conduction defects in acute myocardial
infarction since the introduction of thrombolytic therapy.
AB - OBJECTIVE: To document the frequency of conduction defects and their influence on
prognosis in a large series of patients with acute myocardial infarction who
underwent coronary care during a period when thrombolytic therapy was in common
usage. BACKGROUND: Conduction defects have been associated with an adverse
prognosis following acute myocardial infarction, but there are few data on the
incidence and outcome of conduction defects since the introduction of
thrombolytic therapy. PATIENTS AND METHODS: The study group comprised 1225
consecutive patients with acute myocardial infarction treated in the coronary
care unit from 1 January 1988 to 31 December 1994. Conduction defects were
recorded prospectively and were classified as follows: complete atrioventricular
node block associated with narrow complex escape rhythms; left or right bundle
branch block; bifascicular block; complete heart block involving both bundle
branches. RESULTS: Electrocardiographic data were available in 1220 patients.
Complete atrioventricular node block occurred in 65 (5.3%), left and right bundle
branch block in 29 (2.4%) and 44 (3.6%) bifascicular block in 36 (2.9%) and
complete heart block involving both bundle branches in 20 (1.6%). The more
advanced degrees of block in the bundle branches occurred more commonly in
patients with diabetes, previous infarction. Q-wave infarction, anterior
infarction and left ventricular failure. Survival analysis showed an increased
short- and long-term cardiac mortality in patients with conduction defects,
prognosis worsening as the severity of the conduction defect increased.
CONCLUSION: Conduction defects complicated acute myocardial infarction in 16% of
cases and had a graded impact on the short- and long-term prognosis, patients
with advanced bundle branch involvement faring worst. The data showed a small
decline in the rate of severe conduction defects compared with previous studies,
possibly reflecting the beneficial effects of thrombolytic therapy on infarct
size.
PMID- 9651714
TI - Unstable coronary artery disease in post-menopausal women. Identifying patients
with significant coronary artery disease by basic clinical parameters and
exercise test. IRIS Study Group.
AB - BACKGROUND: The diagnostic information from an ECG taken while at rest and an
exercise test is considered less reliable in women than in men, mostly due to a
high percentage of false-positive tests. This can be explained by a lower pre
test likelihood of coronary heart disease. AIMS: To evaluate the diagnostic
information that can be gained from basic clinical parameters, an ECG and
exercise test in a group of post-menopausal women with symptoms of unstable
coronary artery disease in order to identify patients with significant coronary
artery stenoses. METHODS AND RESULTS: We prospectively studied 200 post
menopausal women admitted to the coronary care unit with symptoms of unstable
coronary artery disease and ECG changes suggestive of ischaemia. The diagnostic
value of common risk factors, myocardial enzymes and an early exercise test were
assessed. A coronary angiogram was performed within 60 days. Median age was 67
years. On admission, 38% had ST depression on an ECG taken while at rest, 76% had
T-wave inversion, and 41% increased enzyme levels. The coronary angiogram
revealed that 15% had no atherosclerosis, 14% had atherosclerosis but not lesion
> or = 50% of luminal diameter and 71% had at least one significant stenosis. Of
patients with known indicators of atherosclerotic disease, all but one had
atherosclerosis visualized on the coronary angiogram. A relative ST depression >
or = 0.1 mV and a low maximum workload at exercise test were strong predictors of
significant coronary artery disease. The positive predictive value of ST
depression was 91% and of low maximum workload 84% CONCLUSION: In post-menopausal
women with signs of unstable angina and ischaemia on an ECG taken while at rest,
the prevalence of coronary atherosclerosis is high, 85%. Contrary to earlier
studies, ST T-changes at the early exercise test had a high positive predictive
value, especially in combination with a low maximum workload with no false
positive results.
PMID- 9651715
TI - Predictors of left ventricular thrombus formation and disappearance after
anterior wall myocardial infarction.
AB - AIMS: This study sought to determine predictors of left ventricular thrombus
formation and resolution after acute anterior wall myocardial infarction. METHODS
AND RESULTS: We have analysed clinical, echocardiographic and angiographic data
in 53 consecutive patients with anterior myocardial infarction. Two-dimensional
and Doppler echocardiographic examinations were performed on days 1, 2, 3 and 7,
after 3 and 6 weeks, and 3, 6, and 12 months following infarction. Coronary
angiography was performed in 44 patients before hospital discharge. Left
ventricular thrombus was detected in 30/53 patients (29/30 in the first week
after infarction). Univariate analysis showed that left ventricular thrombus
formation was associated with a higher initial end-systolic volume index (beta =
0.04, P = 0.001), and end-diastolic volume index (beta = 0.03, P = 0.03), a
larger infarct perimeter (beta = 0.02, P = 0.01), a lower initial ejection
fraction (beta = 0.06, P =0.001), a higher initial wall motion score index (beta
= 1.75, P = 0.023), a higher peak creatine kinase level (beta = 3.90, P = 0.01),
Killip class >1 (beta = 1.11, P = 0.003), infarct expansion (beta = 0.78, P =
0.04), occluded infarct-related artery (beta = -0.87, P = 0.04) and non
thrombolytic therapy (beta = -0.76, P = 0.047). According to the Cox proportional
regression model, independent predictors of thrombus formation after anterior
myocardial infarction were high end-systolic volume index (beta = 0.06, P =
0.001) and high peak creatine kinase level (beta = 5.17, P = 0.046). Thrombus
disappeared in 11/30 (36.7%) patients during one-year echocardiographic follow
up. The only independent predictor of thrombus disappearance after acute
myocardial infarction was the absence of apical dyskinesis 6 weeks after
infarction (beta = -1.53, P = 0.045). CONCLUSIONS: Our data demonstrate that the
best predictor of left ventricular thrombus formation after acute anterior
myocardial infarction is a high initial end-systolic volume. Thrombus resolution
is more likely to occur in patients without apical dyskinesis at the end of the
healing phase of infarction.
PMID- 9651716
TI - Direct percutaneous transluminal coronary angioplasty in acute myocardial
infarction. Predictors of short-term outcome and the impact of coronary stenting.
Study Group of The Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte
(ALKK).
AB - BACKGROUND: Direct percutaneous transluminal coronary angioplasty (PTCA) is
widely accepted in the treatment of acute myocardial infarction since excellent
results had been reported from several small randomized trials. Less favourable
results were observed in large-scale registries. In particular, the use of stents
in acute myocardial infarction has become common practice without documented
evidence of clinical efficacy. METHODS: Data were analysed from a registry of all
consecutive percutaneous transluminal coronary angioplasty procedures from 62
centres in Germany, including 2331 direct percutaneous transluminal coronary
angioplasty in acute myocardial infarction from July 1994 to April 1997. RESULTS:
The overall angiographic success rate of percutaneous transluminal coronary
angioplasty, defined as complete antegrade perfusion of the infarct vessel, was
87%. In-hospital mortality was 11.2%. The most important predictor of death was
the presence of cardiogenic shock in 15% of patients, of whom 52% died. Mortality
in patients without shock was 3.9%. Failed percutaneous transluminal coronary
angioplasty was associated with a mortality of 36%. Further independent
predictors of death were older age, multivessel disease, and anterior myocardial
infarction. Stents were used in 4.1% of the procedures in 1994, increasing to 53%
in 1997. However, this was not accompanied by improved clinical outcome.
Mortality with coronary stenting was 9.9% vs 11.6% without stents (ns).
CONCLUSIONS: Direct percutaneous transluminal coronary angioplasty is a valuable
treatment strategy in acute myocardial infarction, although the results are less
exceptional than reported from some highly specialized centres. Failed
percutaneous transluminal coronary angioplasty seems to be harmful, thus
outweighing much of the benefit from successful procedures. Stents did not
improve the clinical outcome significantly, despite technically successful
placement in 98%. Mortality from cardiogenic shock continues to be excessively
high despite direct PTCA.
PMID- 9651717
TI - Effect of oxygen on sleep quality, cognitive function and sympathetic activity in
patients with chronic heart failure and Cheyne-Stokes respiration.
AB - BACKGROUND: Cheyne-Stokes respiration disrupts sleep, leading to daytime
somnolence and cognitive impairment. It is also an independent marker of
increased mortality in heart failure. This study evaluated the effectiveness of
oxygen therapy for Cheyne-Stokes respiration in heart failure. METHODS: Eleven
patients with stable heart failure and Cheyne-Stokes breathing were studies.
Oxygen and air were administered for 4 weeks in a double-blind, cross-over study.
Sleep and disordered breathing was assessed by polysomnography. Symptoms were
assessed using the Epworth Sleepiness Scale, visual analogue and quality of lift
scores. Cognitive function was assessed by neuropsychometric testing. Overnight
urinary catecholamine excretion was used as a measure of sympathetic nerve
activity. RESULTS: Ninety-seven percent of apnoeas were central in origin. Oxygen
therapy reduced the central apnoea rate (18.4 +/- 4.1 vs 3.8 +/- 2.1 per hour; p
= 0.05) and periodic breathing time (33.6 +/- 7.4 vs 10.7 +/- 3.9% of actual
sleep time; p = 0.003). Oxygen did not improve sleep quality, patient symptoms or
cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 +/- 1.5 vs
4.1 +/- 0.6 nmol.mmol-1 urinary creatinine; p = 0.03). CONCLUSION: Oxygen
stabilized sleep disordered breathing and reduced sympathetic activity in
patients with heart failure and Cheyne-Stokes respiration. We were unable to
demonstrate an effect on either patient symptoms or cognitive function.
PMID- 9651718
TI - Fast pathway ablation in patients with common atrioventricular nodal reentrant
tachycardia and prolonged PR interval during sinus rhythm.
AB - AIMS: This study aimed to clarify the safety and efficacy of selective fast
pathway ablation in patients with atrioventricular nodal reentrant tachycardia
and a prolonged PR interval during sinus rhythm. Such patients have been reported
to have an increased incidence of complete atrioventricular block. METHODS AND
RESULTS: In this study, the earliest retrograde atrial activation during
atrioventricular nodal reentrant tachycardia and right ventricular stimulation
was localized. Fast pathway ablation was then performed in five patients with the
common form of atrioventricular nodal reentrant tachycardia and a prolonged PR
interval. Three of the five patients had almost incessant atrioventricular nodal
reentrant tachycardia. Radiofrequency catheter ablation induced a complete
ventriculo-atrial block during right ventricular stimulation in four patients and
a marked prolongation of ventriculo-atrial conduction during right ventricular
stimulation in one. Non-inducibility of common atrioventricular nodal reentrant
tachycardia with and without isoproterenol was achieved in all five patients. The
PR interval increased from 254 +/- 53 ms to 276 +/- 48 ms and the atrio-His
interval from 172 +/- 46 ms to 192 +/- 45 ms. Second- or third-degree
atrioventricular block did not occur during the ablation procedure. During the
followup of 19 +/- 20 months none of the patients developed symptoms suggestive
of atrioventricular nodal reentrant tachycardia or evidence of second- or third
degree atrioventricular block. CONCLUSION: These data suggest that
atrioventricular node (retrograde) fast pathway ablation can apparently be safely
performed in patients with common atrioventricular nodal reentrant tachycardia
and a prolonged PR interval during sinus rhythm.
PMID- 9651719
TI - Permanent junctional re-entry tachycardia. A multicentre long-term follow-up
study in infants, children and young adults.
AB - AIMS: Permanent junctional re-entry tachycardia is a relatively uncommon form of
re-entry tachycardia with antegrade conduction occurring through the
atrioventricular node and retrograde conduction over an accessory pathway usually
located in the postero-septal region. It was the aim of the study to investigate
the course of permanent junctional re-entry tachycardia with particular regard to
the effectiveness of pharmacological treatment and ablation procedures;
evaluation was performed with respect to the patient's symptoms, tachycardia
rate, frequency of the tachycardia and left ventricular function. METHODS AND
RESULTS: The long-term follow-up of 32 patients with permanent junctional re
entry tachycardia was evaluated. The first presentation with supraventricular
tachycardia occurred between the 27th week of gestation and 27 years. The
tachycardia rate ranged from 100 to 250 beats.min-1. During Holter-ECG, permanent
junctional re-entry tachycardia was documented as present for over 50% of the
time in 24 h in 22 patients (69%). Left ventricular performance was impaired in
nine patients (28%) due to a tachycardia-related cardiomyopathy. Symptoms or
signs of heart failure were mild to moderate in eight and severe in four
patients; 20 patients showed no clinical impairment. Follow-up time was 1 to 31
(mean 10) years; current age of the patients ranged from 1.5 months to 35 (mean =
15 x 3) years. Four patients needed no therapy because of the infrequency of
permanent junctional re-entry tachycardia episodes. Twenty-five patients
initially received antiarrhythmic drugs, which were effective or partially
effective in 14 (56%). Eight of them are still on medical therapy; in five
treatment was discontinued because of absence of symptoms. Eleven patients had
ablation of the accessory pathway during follow-up, three underwent ablation as a
primary procedure. CONCLUSION: Permanent junctional re-entry tachycardia in our
experience is an arrhythmia with a large variety of clinical symptoms. Patients
with a slow tachycardia rate and infrequent episodes of tachycardia may never
develop symptoms and therefore do not need any therapy. Patients with frequent
permanent junctional re-entry tachycardia, a fast tachycardia rate and impaired
left ventricular function need effective therapy. In infancy and early childhood
medical therapy is recommended as a first option, whereas in older and
symptomatic patients catheter ablation is an effective and safe procedure.
PMID- 9651720
TI - Trans-septal catheterization for radiofrequency catheter ablation of cardiac
arrhythmias. Results and safety of a simplified method.
AB - AIM: This study reports on the results and safety of a simplified method of trans
septal catheterization for radiofrequency catheter ablation of cardiac
arrhythmias. METHODS AND RESULTS: Over 5 years, 411 patients underwent trans
septal catheterization for radiofrequency catheter ablation: 388 patients had a
left-sided accessory pathway, 19 a left-sided focal atrial tachycardia, two
atrial fibrillation and two post-infarction ventricular tachycardia. All but one
patient with ventricular tachycardia underwent elective trans-septal
catheterization. In the absence of a patent foramen ovale, puncture of the atrial
septum was performed by using an 8F Mullins sheath and a Brockenbrough needle,
according to the simplified method described in this paper. Trans-septal
catheterization was accomplished in 383/388 patients (98.7%); in 41 patients a
second trans-septal catheterization and radiofrequency catheter ablation was
performed for initial failure or recurrence. Radiofrequency catheter ablation was
successful in 96% of accessory pathway patients, 90% of atrial tachycardia
patients, in both patients with atrial fibrillation and in both patients with
ventricular tachycardia. No complication related to trans-septal catheterization
was observed. CONCLUSION: In experienced hands and according to the method
described in this paper, the elective use of transseptal catheterization for
radiofrequency catheter ablation in a large cohort of patients with cardiac
arrhythmias is feasible, safe and allows successful ablation in the vast majority
of the patients.
PMID- 9651721
TI - Impact of dietary sodium intake on left ventricular diastolic filling in early
essential hypertension.
AB - AIMS: Dietary sodium intake modulates left ventricular hypertrophy in established
essential hypertension independent of blood pressure level. We conducted this
study to elucidate the relationship between sodium intake and left ventricular
structural or functional changes in early essential hypertension. METHODS: Forty
four young male patients (age 25.9 +/- 2.6 years) with mild essential
hypertension that had never been treated and 45 normotensive male control
subjects of similar age were examined. Dietary sodium intake was measured from 24
h urinary sodium excretion, blood pressure from 24 h ambulatory monitoring
(SpaceLabs 90207), left ventricular structure from 2-D guided M-mode
echocardiography, and diastolic filling of the left ventricle (as the main
compound of diastolic function in a young population) by pulse-wave Doppler
sonography. RESULTS: In hypertensive patients, daily sodium excretion correlated
with the ratio of late (A) to early (E) maximum velocity (A/E; r = + 0.27, P =
0.07), velocity time integrals (A/E; r = + 0.54, P < 0.001) as well as atrial
contribution, as a percent of left ventricular filling (VH ATCO; r = + 0.52, P <
0.001) independent of heart rate, whereas the opposite correlations were observed
in normotensive (all P < 0.001). Stepwise multiple regression analysis confirmed
these results. Sodium excretion emerged as the strongest independent determinant
of impaired diastolic filling in hypertensive patients (velocity time integrals
A/E: R(2) = 0.49, beta = 0.57, P = 0.0001; VH ATCO: R(2) = 0.48, beta = + 0.56, P
< 0.0001; Vmax A/E: ns). In normotensive subjects, sodium excretion was a similar
strong, but inverse determinant of diastolic filling (velocity time integrals
A/E: R(2) = 0.40, beta = -0.43, P = 0.0028). Heart rate was a strong determinant
of diastolic filling in hypertensive patients (beta = +0.55, P = 0.0002) and in
normotensive subjects (beta = + 0.34, P = 0.011). Left ventricular mass and end
diastolic volume index were not related to diastolic filling in either group.
CONCLUSION: In early essential hypertension, sodium excretion is correlated with
impaired left ventricular diastolic filling independent of left ventricular mass.
The renin-angiotensin-aldosterone-aldosterone system might be a mediator of the
observed correlation.
PMID- 9651722
TI - Segmental comparison between coronary angiography and positron emission
tomography reveals low predictive value of epicardial flow for viability.
AB - BACKGROUND: The functional significance of the anterograde and retrograde filling
of coronaries on angiography is controversial. METHODS AND RESULTS: Eighteen
patients with 27 severe lesions (> 85% diameter stenosis) after previous
extensive myocardial infarction were selected. The left ventricle was divided
into 33 segments for regional comparison of epicardial flow (as assessed by
angiography) and tissue perfusion as well as metabolism (as measured by 13NH3-
and 18FDG-PET). Viability was defined as normal perfusion (> 80% relative of
maximum 13NH3 activity) or mismatch defect (> 1.2 metabolism/flow ratio). A
method has been developed to register the 'lesion predicted region', determined
on the basis of angiography, in the same polar map as derived from the positron
emission tomography data. Distal to the lesion, the anterograde epicardial flow
was evaluated by Thrombolysis in Myocardial Infarction (TIMI) criteria (TIMI flow
0-3), and retrograde filling was graded on a 0-3 scale (collateral grade 0-3).
TIMI flow grade and retrograde collateral grade in every lesion predicted region
segment were summed to indicate the total segmental epicardial flow. Out of the
594 segments, 369 were associated with a severe lesion. Among them, significantly
higher average perfusion and metabolic activities were found in segments of good
epicardial filling (summed epicardial flow > or = 3) than in the territories of
limited epicardial flow (summed score < 3): 65.4 +/- 17% vs 45.6 +/- 10 (P =
0.001%) and 68.6 +/- 16% vs 47.4 +/- 11% (P = 0.0004), respectively. However,
when we analysed the predictive value of angiographically detectable good
epicardial flow for positron emission tomography viability criteria then the
positive predictive value was found to be as low as 0.5, while the negative
predictive value was considerably higher (0.82). CONCLUSION: After myocardial
infarction, angiographically detectable limited epicardial flow reveals scarred
segments while good epicardial contrast filling does not necessarily indicate
maintenance of nutritive function.
PMID- 9651723
TI - Impaired diastolic suction during coronary angioplasty.
PMID- 9651724
TI - Harmful effect of enalapril on left ventricular remodelling in patients without a
severe residual stenosis after acute anterior wall infarction?
PMID- 9651725
TI - Serum lactate dehydrogenase activity: indicator of the development of pneumonitis
induced by amiodarone.
PMID- 9651726
TI - Arginine consumption in coronary disease.
PMID- 9651727
TI - An association of an antibody against Chlamydia pneumoniae and coronary heart
disease observed in Japan.
PMID- 9651728
TI - Catecholamines: the cardiovascular and neuroendocrine system.
AB - The development of profound autonomic dysfunction and of neuroendocrine
activation characterizes and possibly contributes to the progression of heart
disease to congestive heart failure. Sympathetic activation is a generalized
process and the proposed mechanisms for neurohumoral activation include decreased
input from excitatory afferences and increased input from excitatory chemoceptors
and metabaroceptor. These phenomena vary to a great extent in different subjects:
in the more impaired patients, renal and cardiac overflow of catecholamines can
increase three- and ten-fold, respectively, accounting for about 60% of the
increase of noradrenaline in congestive heart failure. Efficient methods to
quantify sympathetic cardiovascular influences and neuroendocrine indices have
been developed and it has been recognized that sympathoneural activation
independently predicts the survival of patients. The pathophysiological role and
the clinical relevance of neuroadrenergic abnormalities also constitute the
grounds for the understanding of the therapeutic benefit obtained with
interventions aimed at mitigating the harmful consequences of adrenergic
hyperactivity.
PMID- 9651729
TI - Methods to quantify sympathetic cardiovascular influences.
AB - This paper will critically review the main features of the various techniques
(plasma noradrenaline assay, noradrenaline spillover technique, microneurographic
recording of postganglionic muscle sympathetic nerve and power spectral analysis
of blood pressure and heart rate signals in specific bands) currently employed to
assess sympathetic cardiovascular control in humans. After highlighting the
advantages and limitations of each approach, the paper will describe some of the
results obtained by employing the above mentioned techniques to detect
abnormalities in sympathetic cardiovascular tone in physiological and
pathological conditions.
PMID- 9651730
TI - Effect of sympathetic overactivity on cardiovascular prognosis in hypertension.
AB - Increased sympathetic tone is found in about 30% of patients with hypertension.
This abnormality is closely associated with the metabolic syndrome of
dyslipidaemia and hyperinsulinaemia. In this short review we discuss the
mechanisms by which sympathetic over-activity could cause the metabolic syndrome.
Sympathetic stimulation enhances cardiac and vascular hypertrophy. Left
ventricular hypertrophy is a strong predictor of poor cardiovascular outcomes.
Hypertrophy of resistance vessels accelerates hypertension, whereas hypertrophy
of smaller coronary vessels limits coronary reserve and increases tendency for
coronary spasms. Epidemiologically, high haematocrit is associated with
hypertension and is recognized as an independent coronary risk factor.
Sympathetic stimulation increases haematocrit through an increase of post
capillary vascular resistance. Sympathetic over-activity is also associated with
platelet activation which may further add to the risk of coronary thrombosis in
neurogenic hypertension. Tachycardia, which is due to increased sympathetic and
deceased parasympathetic tone, is a hallmark of neurogenic hypertension. Fast
heart rate is a strong predictor of coronary events and sudden death. The
mechanisms by which tachycardia increases the cardiovascular risk are outlined.
PMID- 9651731
TI - Relevance of heart rate as a prognostic factor in patients with acute myocardial
infarction: insights from the GISSI-2 study.
AB - AIMS: It is as yet undefined whether simple indexes of autonomic balance such as
heart rate (HR) may play a role in risk stratification in patients with acute
myocardial infarction (MI). The aim of this study was to quantify the prognostic
significance of HR from the surface ECG obtained both at entry and at discharge,
in a large population of patients all treated with fibrinolysis during the acute
phase and having confirmed acute MI. METHODS AND RESULTS: Surface ECGs obtained
at entry and at discharge in patients with confirmed MI enrolled in the GISSI-2
study, a large multicentre trial of different thrombolytic agents, were
retrieved. Heart rhythm was evaluated and HR was measured; these data were then
added to the main database of GISSI-2 allowing a complete evaluation of the
prognostic significance of HR. Patients not in sinus rhythm or with grade 2-3
atrioventricular block were excluded. The prognostic significance of HR (cut-offs
predefined at 60, 80, 100 beats.min-1) at entry for in-hospital mortality and at
discharge for 6-month mortality was evaluated in the general population and in
predefined subgroups. Multivariate analyses were used to assess the independent
prognostic value of HR. A total of 8915 patients (more than 70% of the original
population) were suitable for the analysis. There was a progressive increase in
mortality with increasing HR in the general population (from 7.1% for HR < 60
beats.min-1) to 23.4% for HR > 100 beats.min-1) and in the predefined subgroups.
Multivariate analysis showed that HR exerted an independent prognostic
significance. Data for analysis of HR at discharge were available for 7831
patients. Consistent with the data observed at entry, a progressive increase of 6
month mortality with increasing HR was present in the general population (from
0.8% for HR < 60 beats.min-1) to 14.3% for HR > 100 beats.min-1) and for the
different predefined subgroups. Multivariate analysis confirmed the independent
prognostic significance of HR. There was no relation between HR and the incidence
of fatal and non-fatal reinfarction. CONCLUSION: The present study indicates that
HR values from a standard 12-lead ECG independently predict mortality in patients
with acute MI during the in-hospital phase and after discharge. This simple index
appears very useful for risk stratification in clinical practice.
PMID- 9651732
TI - Effect of calcium antagonists on sympathetic activity.
AB - OBJECTIVE: We evaluated the effects of calcium antagonists on sympathetic
activity in hypertensive patients by searching Medline for English language
articles published between 1975 and May 1996 using the terms calcium antagonists,
sympathetic nervous system and catecholamines. METHODS: Data from clinical
studies reporting only the effects of calcium antagonists on blood pressure,
heart rate and plasma norepinephrine (NE) levels in patients with hypertension
were analysed according to class of calcium antagonist (dihydropyridine vs non
dihydropyridine), their duration of action (short-acting (SA) vs long-acting
(LA)) and treatment duration. RESULTS: We identified 63 studies involving 1252
patients. Acutely after single dosing, SA calcium antagonists decreased mean
arterial pressure by 13.7 +/- 1.1% and increased heart rate by 13.7 +/- 1.4% and
NE levels by 28.6% +/- 2.5%. Change in NE levels correlated with change in heart
rate (r = 0.59, P < 0.01) and inversely with change in arterial pressure (r =
0.46, P < 0.05) in patients taking dihydropyridine calcium antagonists acutely.
With sustained therapy, both classes of SA calcium antagonists increased NE
levels. Whereas NE levels remained slightly elevated and heart rate unchanged
with LA dihydropyridine calcium antagonists, both heart rate and NE levels
decreased with LA non-dihydropyridine calcium antagonists. SA calcium antagonists
stimulate sympathetic activity when given acutely and over the long term,
irrespective of their molecular structure. In contrast, sympathetic activation is
less pronounced with LA dihydropyridine calcium antagonists and falls with LA non
dihydropyridine calcium antagonists. CONCLUSIONS: The present findings offer a
possible pathophysiological explanation for the increase in morbidity and
mortablity observed in some studies using SA calcium antagonists.
PMID- 9651733
TI - Role of sympathetic nervous system in hypertension and effects of cardiovascular
drugs.
AB - The sympathetic nervous system (SNS) plays an important role in the regulation of
cardiac performance and peripheral circulation. Changes in SNS activity measured
as catecholamines in plasma or organ spillover have been implicated in the
pathogenesis of hypertension. Recent studies using microneurography to directly
assess peripheral sympathetic nerve activity have demonstrated an increase in
sympathetic activity in patients with borderline hypertension at rest and during
hypoxia. We have recently shown that resting muscle sympathetic nerve activity is
comparable in offspring of hypertensive and normotensive parents. However, during
mental arithmetic the increase in muscle sympathetic nerve activity and blood
pressure was significantly more pronounced in offspring of hypertensive than in
offspring of normotensive parents, but resting blood pressure was in the
normotensive range and comparable in both groups. These data indicate that the
response to mental stress results in a more pronounced activation of SNS in
normotensive subjects with a genetic background of hypertension. In other
cardiovascular disease states such as acute myocardial infarction and heart
failure activity of the SNS may determine prognosis significantly. Some calcium
antagonists which are successfully used to treat patients with hypertension and
stable angina pectoris may have unfavourable effects in patients with impaired
left ventricular function. This could be due in part to baroreceptor-mediated
activation of the SNS, an effect which seems to be related to pharmacokinetics
and pharmacodynamics of the drugs. In contrast, angiotensin converting enzyme
inhibitors seem to directly decrease sympathetic nerve activity. This may explain
at least in part their beneficial effects in patients with impaired left
ventricular function. Thus, the SNS as a regulator of the cardiovascular system
also plays an important role in the pathophysiology of cardiovascular diseases
such as hypertension, myocardial infarction and heart failure. Furthermore, drug
therapy could have a significant impact on the activity of the SNS.
PMID- 9651734
TI - The sympathetic nervous system in hypertension: differing effects of drug
treatment.
PMID- 9651735
TI - The neuroendocrine and sympathetic nervous system in congestive heart failure.
AB - A review of recent randomized clinical trials has shown that neurohormonal
activation starts early in the natural history of left ventricular dysfunction
and levels of the circulating hormones increase in proportion to the severity of
heart failure. Most studies suggest that high levels of neurohormones predict a
poor prognosis. Among the several neurohormones, the sympathetic system is the
one which is activated earlier, it increases in proportion to the severity of the
disease and has a negative prognostic implication. These concepts have been also
proven in untreated patients. Augmented sympathetic activity in the syndrome of
heart failure is initially beneficial, appears to be adaptive and helps support
blood pressure and cardiac output. Prolonged and excessive sympathetic activation
has deleterious effects with adverse consequences at both cardiac and vascular
levels which aggravates the clinical status of the syndrome and negatively
affects its prognosis. Evidence is accumulating that, contrary to popular belief,
beta-blockers may be beneficial in heart failure by inhibiting sympathetic
activation. In addition to neuroendocrine activation, another class of
biologically active molecules, termed cytokines, are excessively secreted by
cells in heart failure. Important among these cytokines are tumour necrosis
factor-alpha and interleukin-6. They appear to exert deleterious effects on the
heart and circulation which may be also involved in the progression of heart
failure.
PMID- 9651736
TI - Beta-blockers in heart failure.
AB - Beta-blocker therapy for heart failure has gained popularity as a result of
recent growing evidence that this group of drugs can reverse or slow the
progressive left ventricular dilation that characterizes heart failure. Although
the mechanism of this favourable effect on remodelling remains unclear, the
present evidence indicates that at least a portion of the long-term benefit of
these drugs is mediated through their beta-blocking action. A direct effect on
myocyte and interstitial growth may be a key factor in their ability to inhibit
the remodelling process. The growing database will eventually raise the
possibility that all patients with left ventricular dilation should take one of
these drugs. A better understanding of differing mechanisms in individual
patients would ideally provide selectivity in the therapeutic approach.
PMID- 9651737
TI - Catecholamine levels and treatment in chronic heart failure.
AB - Neurohormonal activation is well studied in chronic heart failure, and covers
aspects such as abnormalities of plasma catecholamines, particularly since plasma
noradrenaline levels have been found to predict impaired prognosis in heart
failure patients. This review will concentrate on the information available on
circulating levels of adrenaline and noradrenaline. It will discuss how
catecholamine levels change during different disease stages from myocardial
infarction to severe chronic heart failure. It has been clearly shown that
angiotensin converting enzyme (ACE) inhibitors exert particularly beneficial
effects in heart failure patients with raised catecholamine levels. Nevertheless,
reviewing how a variety of drug and non-drug interventions affect catecholamine
levels and patients' survival, it is concluded that the effect on catecholamine
levels does not directly correlate with a survival benefit of the respective
intervention. Despite their prognostic significance, due to the development of
new prognostic markers for patients with chronic heart failure, the overall
clinical value of spot catecholamine levels remains limited.
PMID- 9651738
TI - The sympathetic nervous system and ischaemic heart disease.
AB - The sympathetic nervous system, coronary artery disease and myocardial ischaemia
are related in different ways. First, the sympathetic system may be involved in
the process of atherosclerosis through platelet activation and subsequent
platelet-derived growth factor formation and by inducing mechanical injury to the
vascular wall as a result of increased blood pressure and increased flow
velocity. Secondly, sympathetic control of coronary vasomotor tone, which under
normal conditions is not important, becomes functionally significant once
coronary artery disease endothelial dysfunction has occurred. Under these
circumstances, increased sympathetic adrenergic tone may lead to coronary
vasoconstriction and, as myocardial oxygen demand increases concomitantly,
myocardial ischaemia may ensue. Alternatively, myocardial ischaemia activates
several neurohormonal systems, such as the sympathetic and, during more severe
ischaemia, the circulating renin-angiotensin system. This leads to systemic and,
possibly, coronary vasoconstriction and thus to further myocardial ischaemia.
Prolonged myocardial ischaemia results in progressive norepinephrine release from
the heart, reaching extracellular levels as high as 100-1000 x plasma
concentrations. As cardiac beta-receptor density rises simultaneously,
sympathetically-induced irreversible myocardial damage may occur, although
through concomitantly increased beta-receptor kinase activity the beta-receptor
may become functionally inactive. To counteract the detrimental effects of
enhanced sympathetic activation on the heart, beta-blockade appears to be the
proper choice. However, acute beta-blockade may lead to more profound ischaemia
induced neurohormonal activation and hence to vascular constriction through
unoccupied alpha-receptors. In contrast, under ischaemic conditions and with
concomitant beta-blockade, acute alpha-blockade does improve subendocardial flow
and reduces myocardial ischaemia. A novel approach to anti-ischaemic therapy,
which relates to modulating ischaemia-induced sympathetic activation, is through
ACE inhibition. ACE inhibitors affect myocardial ischaemia by reducing
neurohormonal activation and related systemic and coronary vasoconstriction.
These acute effects may become more important over time, as coronary endothelial
function improves following long-term ACE inhibition. A large multicentre
controlled trial comparing ACE inhibition with placebo in patients with coronary
artery disease, the EUROPA (EUopean trial on Reduction Of cardiac events with
Perindopril in stable coronary Artery disease), which is currently underway,
addresses the issue of whether ACE inhibition does in fact offer a novel approach
in myocardial ischaemia.
PMID- 9651740
TI - Blastoderm structure, cell migration and formation of the embryonic shield during
gastrulation in the carp (Cyprinus Carpio); a scanning electron microscopic
study.
AB - This paper describes an ultrastructural study of the cell movements during the
gastrulation of the common carp, Cyprinus carpio, using scanning electron
microscopy. The morphology of the deep cells was studied in several consecutive
stages ranging from 0-100% epiboly. Furthermore, the formation of the embryonic
shield was followed from its earliest appearance at 50% epiboly onwards. This
paper gives morphological evidence for the existence of two different pathways
for involving and convergent movements. Firstly, cells may move along the inner
surface of the not (yet) involuted cells. Secondly, a much smaller group may use
the YSL as their substrate. These results are discussed in the light of the
hypothesis that the two migrating cell populations may be differently induced,
subsequently leading to the formation of mesoderm and endoderm.
PMID- 9651739
TI - The autonomic nervous system and sudden death.
AB - The knowledge progressively accumulated on the relation between changes in
autonomic activity and cardiac mortality, particularly in the setting of acute
myocardial ischaemia, has turned during the last decade toward the potential
prognostic value of markers of autonomic activity. Two of these markers, heart
rate variability and baroreflex sensitivity, have gained progressive popularity.
This chapter reviews some of the experimental observations that were instrumental
for the novel clinical approach to post-myocardial infarction risk stratification
based on the use of autonomic markers as risk stratifiers. It then focuses on
clinical studies with special attention for a very recent multicentre prospective
study (ATRAMI) carried out in almost 1300 post-myocardial infarction patients and
aimed at the evaluation of the prognostic value of both heart rate variability
and baroreflex sensitivity. Finally, some pathophysiological considerations are
added to clarify the legitimacy, or lack of it, of the terminology currently used
in clinical studies based on autonomic markers.
PMID- 9651741
TI - Ultrastructure of rat atrial tissue after either perfusion-or immersion-fixation
both in vivo and in vitro study: comparison of methodological reliability.
AB - The present study compares, from a morphological point of view, the possible
differences between perfusion- and immersion-fixation techniques performed on rat
myocardium in order to evaluate their reliability. The data we obtained showed
that when the two techniques are carried out with particular care, they do not
present significant differences in tissue preservation. Furthermore, we also
evaluated the ultrastructural of rat myocardium at the end of in vitro
experiments. In this case, signs of subcellular changes, such as vacuolar
degeneration, swollen mitochondria, intermyofibrillar myelin-like figures and
enlargements of non specialized junctions of the intercalated discs can
frequently occur. So, our results indicate that the morphological integrity of
myocardium is not completely preserved during in vitro investigations.
PMID- 9651742
TI - Sublethal alterations and sustained cell proliferation associated with the
diethylstilbestrol-induced renal carcinogenesis in male Syrian golden hamsters.
AB - The current study was initiated to explore the sublethal alterations and the
tissue damage occurring in the hamster kidney during diethylstilbestrol-induced
renal carcinogenesis. A total of 49 male Syrian golden hamsters (35 treated and
13 control animals) was utilized in the experimental procedure. Chronic exposure
to diethylstilbestrol was achieved by s.c. insertion of implants containing 25 mg
diethylstilbestrol. For long-term observation, adequate blood level of
diethylstilbestrol was insured by renewing the implant every 2 months.
Experimental groups (n = 4 to 9) were terminated 1, 2, 4, 6, 9 and 11 months
after initial implantation for morphological examination of the kidney.
Diethylstilbestrol carcinogenicity in this experimental model was confirmed by
the observation that most animals undergoing drug exposure for 6 months or more
exhibited renal neoplasms. The most striking nonneoplastic morphological
abnormality disclosed by histological and cytological examination consisted in
the accumulation of granular inclusions in proximal tubule cells. In renal
tissue, the extent of cell proliferation determined by PCNA labeling
progressively increased along with the duration of diethylstilbestrol exposure
and suggested a sustained proliferative response in altered proximal tubules. The
present data suggest that an impairment of functional tubular regeneration could
promote, as well as the estrogen genotoxic effect, the tumorigenicity of
diethylstilbestrol in the kidney of male hamsters.
PMID- 9651743
TI - Light and scanning electron microscopic study of the palatine mucosa of nine
banded armadillo (Dasypus novemcinctus).
AB - The three-dimensional structure of the lamina propria of the hard and soft
palatine mucosa of the nine-banded armadillo was observed by scanning electron
microscopy. Sodium hydroxide cell maceration method was applied to demonstrate
the architecture of the connective tissue papillae. The palatine mucosa of the
armadillo had a triangular shape and measured appr. 6.5 cm length. The hard
palate showed 9 transverse palatine plicae while the soft palate was smooth. In
the 10% NaOH treated specimens, the lamina propria of the hard palatine mucosa
showed numerous connective tissue papillae with a general finger-like shape.
These structures were composed by a meshwork of collagen fibers arranged in
several directions. On the other hand, the connective tissue papillae of the soft
palate mucosa were scattered and small. Numerous openings of glandular ducts with
circular or elliptical shape were located in the interplicae area and in the soft
palate.
PMID- 9651744
TI - A quantitative study of the ventricular myoarchitecture in the stage 21-29 chick
embryo following decreased loading.
AB - During the early developmental period, ventricular myoarchitecture undergoes a
transition from a smooth-walled cardiac tube, to left and right ventricular
chambers filled with a sponge-like network of trabecular struts. We measured the
quantitative changes of ventricular myocardium properties in normal stage 21-29
chick embryos and after chronic verapamil suffusion, which is known to decrease
work load and decelerate ventricular growth. The morphologic parameters (compact
layer thickness, ventricular wall composition, porosity of different layers and
trabecular orientation) were determined from scanning electron micrographs of
transversely dissected perfusion-fixed hearts. A vascular bed of stage 21 chick
embryos was suffused with 1 ng of verapamil at 1 microliter per hour up to stages
24, 27 and 29 via a miniosmotic pump. From stage 24, the thickness of the compact
myocardium in the left ventricle was greater than that of the right. The increase
in thickness was minimal between stages 24 and 27, while the predominantly
radially arranged trabeculae comprised up to 75% to total myocardial mass. The
ratio of intertrabecular spaces to trabeculae (local porosity) decreased form the
ventricular center (70%) towards the compact myocardium (0%). In verapamil
treated embryos, the hearts were smaller and showed delayed development. The
compact myocardium was thinner than normal, and the proportion of trabeculae was
higher than in controls. The local porosity values were similar in control and
experimental groups. Decreased load resulted in delayed growth and morphogenesis,
expressed as persistence of trabeculae and a thinner compact myocardium.
Embryonic heart pumping function is largely based on extensively developed
trabeculation with regionally different properties.
PMID- 9651746
TI - EUROSON 98--SFAUMB 98. 10th Congress of EFSUMB--19th Congress of SFAUMB. March 26
30, 1998, Tours, France. Abstracts.
PMID- 9651745
TI - Sensory innervation of myosin heavy chain-based types of chicken intrafusal
fiber.
AB - Chicken intrafusal fibers that had been categorized as slow or fast contracting
by their reactions with monoclonal antibodies against myosin heavy chains (MHC)
at polar regions were examined at the equator and neighboring juxtaequator to
determine if fiber type-specific morphologies were also present at the sensory
region. The parameters chosen for examination were contractile filaments,
distribution of acetylcholinesterase and sensory innervation. Evaluation of
acetylcholinesterase was included to define the proximal limit of motor terminal
distribution. At the equator actin was primarily restricted to a thin layer
beneath myosensory junctions. Myosin heavy chains at the equator and the
juxtaequator were more evenly distributed. Although absent from the synaptic side
of the sensory region, acetylcholinesterase activity was present on the
extrasynaptic side. Plots of diameters of sensory axon collaterals and of sensory
endings yielded continuous spectra instead of distinct peaks. Taken together,
these features indicated a uniform equatorial morphology. However, sensory
terminals to fast intrafusal fibers were longer and narrower than those to slow
intrafusal fibers, and typically more terminals impinged on fast than on slow
intrafusal fibers. Moreover, in the larger spindles short sensory terminals were
most prevalent near the equatorial-juxtaequatorial junction, the region where in
mammalian intrafusal fibers secondary sensory axons make contact. The differences
seen in sizes and distributions of terminals suggest that, despite the lack of
type-specific morphologies at the sensory region of chicken intrafusal fiber
types, some level of functional separation is maintained there.
PMID- 9651747
TI - Deconstructing the dialectic.
AB - The author examines some of the newly offered ideas and concepts about the
interaction of the patient and the analyst. This interaction is termed a
dialectic in the sense of interacting forces and this study is called a
deconstruction, which is an effort to see how unstable and self-contradictory
these new ideas may be. They are examined in terms of viewpoints of analysis as a
developmental process, the location of the data of analysis, and the technical
modifications that follow from this changed theoretical vision. A clinical
example is offered to demonstrate the resultant problems. The suggested present
status of the impact of these new ideas is that of a family of related concepts
with no unifying theory.
PMID- 9651748
TI - The changing aims of psychoanalytic psychotherapy. An integrative perspective.
AB - The purpose of this paper is to relate traditional psychoanalytic ideas on aims
and outcomes to the changing world of contemporary psychoanalytic psychotherapy,
with its financial constraints and theoretical and technical innovations. An
emphasis on splitting rather than repression, on the nature of the attachment
between therapist and patient, and on realistic goals and modest change all
characterise contemporary perspectives. Recent developments in the cognitive
behavioural psychotherapy literature indicate possible areas of overlap with
psychoanalytic psychotherapy. Attachment theory proposes that patient-therapist
attunement is likely to be a key variable in outcome. Since attunement is
intrinsically responsive rather than directive, the paradox of psychoanalytic
'aimlessness' is inherent in the nature of psychoanalytic psychotherapy.
PMID- 9651749
TI - From simplicity through contradiction to paradox. The evolving psychic reality of
the borderline patient in treatment.
AB - The thesis of this paper is two-fold. First, it proposes that the psychic reality
of the borderline patient evolves in a three-step process during the analytic
treatment. These steps include: (i) experiencing and presenting disparate psychic
states without the awareness of inherent contradictions, (ii) observing,
acknowledging, and mending the splits responsible for these contradictions, and
(iii) developing a capacity for feeling and accepting paradox, i.e. coexistence
of multiple meanings at different levels of abstraction. Second, the author
suggests that this three-step movement vis-a-vis the associative material takes
place first within the analyst's reverie and then in the patient's psychic
reality. The analyst's holding, unmasking, bridging and depth-rendering
interventions (and the vicissitudes of identification) make the patient's advance
possible. The author presents two clinical vignettes, highlighting these
hypotheses and their technical implications. A vignette from the non-clinical
realm of a mother's interaction with her children is also included in the hope of
demonstrating a developmental 'Anlage' of the analyst's interventions outlined
above. The paper concludes with the observation that the practising analyst also
needs to traverse a 'simplicity-contradiction-paradox' sequence in his view of
the divergent theoretical approaches to the analytic understanding and treatment
of severe character pathology.
PMID- 9651750
TI - The poignant, the excessive and the enigmatic in sexuality.
AB - The author offers a contribution to redressing a certain lack of theorization
concerning the specific power and meaning of sexuality. This begins with George
Klein's suggestion that it is the quality of a specific, poignant sensuality that
characterizes sexuality. Bataille's ideas about the violent and excessive aspects
of eroticism provide some answers to the question of what makes for this special
poignant quality. Bataille captures a profound link between the sacred and the
erotic with regard to their both being linked with taboos and their transgression
as opposed to habitual 'work mentality' and established order. The excessive
dimension highlighted by Bataille is complemented in the work of Laplanche about
sexuality as opposed to 'functional', self-preservative ego needs, and the excess
of the 'enigmatic message' transmitted by the mother while satisfying the
infant's ego needs that establishes the infant's unconscious and sexuality.
Losing the nutritive object, a process of fantasizing sets in; the influx of
strong sensations that cannot yet be integrated spills over into libidinal
excitement. The gap between the other's excess and the child's limited resources
can then be sexualized. A picture emerges of non-procreative sexuality as foreign
to ordinary experience and as transcending one's limits.
PMID- 9651751
TI - A look at the Salome-Freud correspondence.
AB - The author notes that the changing emphasis of the correspondence between Lou
Andreas-Salome and Sigmund Freud over the years reflects certain aspects of the
development of every analyst. Her contributions are shown to illustrate the
evolution of the analyst's relationship with theory and the growth of his or her
clinical capacity and involvement. Two phases in the analyst's clinical
progression are stated to be discernible in the correspondence, marked by changes
of direction that mirror the changing nature of her relationship with Freud.
Theoretical considerations predominate in the first phase, while clinical aspects
gradually come to the fore in the second. Freud is seen to be offering Salome a
kind of supervision by letter. Lou's underlying transference to Freud also
emerges from the correspondence, its two aspects being the relationship to a big
brother and to a father respectively. Freud's complementary transference to
Salome is also discussed, partly in connection with her relationship with his
daughter Anna. The author's arguments are supported by extensive quotations from
the correspondence, biographical works and Lou Andreas-Salome's published diaries
and reminiscences. Last but not least, her relationship with Freud in the
author's view indirectly raises the issue of that of any analyst to the founder
of psychoanalysis.
PMID- 9651752
TI - The Ambulatorium: Freud's free clinic in Vienna.
AB - At the close of World War I, Freud proposed the creation of clinics providing
free treatment, in the first of a series of politically liberal statements
promoting the development of a kind of institution that is rarely associated with
psychoanalysis today. Using archival and oral history research methods, this
study offers a descriptive and statistical history of the Vienna Ambulatorium,
the free psychoanalytic clinic and child guidance centre created--we can now
surmise--under Freud's direction. Presented within the cultural context of
central Europe's inter-war rush of progressivism in 'Red Vienna' and in Germany's
Weimar Republic, little-known aspects of the history of psychoanalysis emerge.
From 1922 to 1936, the staff of the Ambulatorium treated gratis patients of all
ages and social classes, ranging from professional to unemployed. Candidates too
were analysed at no cost. Reflecting the urban energy of his era, Freud believed
that psychoanalysis could be both productive and free of cost. What emerges is an
unexpectedly activist, community-oriented profile of some of the earliest
participants in the psychoanalytic movement.
PMID- 9651753
TI - Never before and never again. The compulsion to repeat, the fear of breakdown and
the defensive organisation.
AB - In this clinical communication, the author discusses the compulsion to repeat
past trauma within the area of personal omnipotence provided in the transference,
the fear of breakdown that may arise in the course of an analysis, and the
defensive organisation deployed by the patient in the interest of survival. The
development of and some connections between the compulsion to repeat, the fear of
breakdown and the defensive organisation are illustrated and discussed in light
of the writings of Freud, Winnicott and various Kleinian authors and some of the
factors that may contribute to the emergence of the fear of breakdown--those
inherent in both the analytic setting and in the early history and character of
the patient--are exemplified by the case of one analysand which is offered to
highlight further the dynamics of a particular variety of defensive organisation
against breakdown.
PMID- 9651754
TI - Chronicle of an incest foretold.
AB - In this paper the author discusses the situation of children handed over to
grandparents or to other relatives of the natural parents to be brought up. She
notes that such children are faced with the riddle of their own filiation and
postulates that this scenario often conceals an oedipal fantasy to the effect
that the child concerned is the fruit of an incestuous relationship between a
grandparent and the relevant parent. Following the example of Freud, the author
adduces literary models for illustration. As with the Oedipus of Sophocles, the
author shows how efforts to thwart the workings of fate actually bring about the
consummation of the tragedy in the form of incest, which is favoured by the
confused oedipal configuration in the families of handed-over children. The main
argument is based on the characters and situations of two novels by Gabriel
Garcia Marquez, written at different times in his life. With reference to the
psychoanalytic literature on artistic creativity, the author shows the importance
of the mid-life crisis in determining how Garcia Marquez came to terms with the
fact of having himself been entrusted to grandparents as a child and how this
situation is reflected in the works concerned.
PMID- 9651755
TI - Illusion and uncertainty in psychoanalytic writing.
AB - Psychoanalytic writing may be viewed as a particular version of creative process.
As such, it evokes many of the self and object-related anxieties and conflicts
associated with creative expression. This paper considers the role of illusion in
facilitating an entry into the psychoanalytic writing process in the light of
contemporary relational and feminist perspectives. It is suggested that the
writer who struggles to write may engage certain real or internalized object
experiences to retreat to a transitional idealized self-state and to enter the
writing process. Two variants of this subjective state are described, based on
Winnicott's notion of 'being' and 'doing' as underlying dimensions of human
experience. Each self-state excludes a particular set of self- and object-related
anxieties and creates a temporary illusion of creative certainty. That illusion
helps the writer temporarily to avoid self-doubt and anxiety in order to enter
the creative arena Ultimately, however, the protected writing space must expand
if the writer is to address and integrate the world of psychoanalytic ideas
within the writer's own creative process. This process is illustrated by a
description of the evolution of my own experience as a psychoanalytic writer.
PMID- 9651756
TI - Emotional processing: the mind-body connection.
PMID- 9651757
TI - Presentation of clinical material on sexuality.
PMID- 9651758
TI - Sexuality in the analysis of adolescents: its impact on the transference
countertransference.
PMID- 9651759
TI - Presentation of clinical material on sexuality.
PMID- 9651760
TI - Mass sexuality/private sexuality.
PMID- 9651761
TI - The Holocaust.
PMID- 9651762
TI - Castration as an organiser of bisexuality.
PMID- 9651764
TI - Film reviews guest editorial.
PMID- 9651763
TI - Psychosis.
PMID- 9651765
TI - Robert Caper on 'A mind of one's own' (IJPA, 78: 265-278)
PMID- 9651766
TI - Hitchcock's Vertigo: the collapse of a rescue fantasy, by Emanuel Berman (Int. J.
Psychoanal., 78: 975-996)
PMID- 9651767
TI - Historicising the origins of Kleinian psychoanalysis (IJPA, 78: 1165-1182)
PMID- 9651768
TI - 'The elusive concept of "Internal Objects" (1934-1943)' by R. D. Hinshelwood.
PMID- 9651769
TI - Defatted, gas-sterilised cortical bone allograft for posterior lumbar interbody
vertebral fusion.
AB - In posterior lumbar interbody vertebral fusion operations, variously sized,
rectangular shaped, defatted, freeze-dried, gas-sterilised cortical bone
allografts were used in combination with cancellous bone autografts from excised
posterior elements. Single-level fusion, with or without internal fixation, was
undertaken in 38 patients aged 50 years or less with disc herniation or a failed
discectomy (the younger group) and in 33 women aged 60 years or more with
degenerative spondylolisthesis (the older group). Of the various observable
indicators of union, changes in the allograft-host interface alone proved to be
of practical use. The incidence of nonunion in patients managed with pedicle
screws, with a hook and rod system or without internal fixation was 0 of 8
patients; 1 of 14 patients; and 3 of 16 patients, respectively, in the younger
group, and 0 of 11 patients; 0 of 8 patients; and 2 of 14 patients, respectively,
in the older group. Of the six patients with nonunion, three had persistent low
back pain and only two had mobility of the fused segment which was evident on
lateral radiographs during flexion and extension. No patient had graft collapse.
The decrease in the height of the intervertebral space, chiefly due to settlement
of the allograft into the vertebral bodies, in the younger and older groups
averaged 1.1 and 1.6 mm, respectively. We concluded that this simplified
technique is mechanically sound and effective in maintaining the height of the
intervertebral space. Even when the graft failed to unite, fibrous union could be
obtained without graft collapse. Combination with a simple internal fixator, such
as a compression rod, facilitates bone union.
PMID- 9651770
TI - Anterior lumbar vertebral translation following translaminar screw fixation. A
report of five cases.
AB - Translaminar screw fixation is a good procedure for posterolateral spinal fusion
of one or two motion segments. Anterior translation of the upper fused vertebra
occurred in 5 of our patients following this procedure. A further fusion with
pedicle screw fixation was needed in 2 of them. This complication has been
previously reported after decompression operations on the lumbar spine.
Translaminar screwing produces slight posterior distraction which pushes forward
the upper vertebra. This procedure should be avoided in cases with even minimal
anterior translation before operation. Translaminar screw fixation is an ideal
technique for fusion of a degenerated segment when the upper vertebra has slipped
posteriorly.
PMID- 9651771
TI - Infantile idiopathic scoliosis in the newborn.
AB - We have reviewed 7 patients (5 boys and 2 girls) with infantile idiopathic
scoliosis which was present at birth and was diagnosed at ages from 1 day to 1
month. The mean follow up was 16 years. The objectives were to discover whether
intrauterine forces play a role in the aetiology and to determine whether early
treatment of a potentially progressive curve can induce resolution. Two infants
were male conjoined twins and were united by skin over the posterior sacrum. Six
infants had a rib vertebral angle difference greater than 20 degrees in the first
radiograph and 5 had stiff curves. In 2 with flexible curves, the deformity
disappeared by the end of the first year. The 5 with stiff curves were treated
conservatively for 6 to 24 months. Growth has now been completed in 5; 4 have a
straight spine and one developed an adolescent curve of 26 degrees. The 2 who are
still growing have no scoliosis. Intrauterine moulding was only demonstrated in
the conjoined twins. There was a correlation between the rib vertebral angle
difference above 20 degrees and the rigidity of the curve. Early treatment of a
potentially progressive curve can lead to resolution.
PMID- 9651772
TI - Osteotomy at the knee for advanced cases of Kashin-Beck disease.
AB - The results of 247 osteotomies at the knee were analysed in 195 patients with
Kashin-Beck disease. Since 1983, 37 varus and 210 valgus deformities have been
operated on. Supracondylar osteotomy was carried out so that there is a cortical
spike in the distal metaphysis which is impacted into the femoral condyle. A U
shaped tibial osteotomy is made 0.5 cm below the growth plate and around the
insertion of the patellar ligament. The mechanical axis is corrected and
stability obtained by impacting the fragments; internal fixation is not used.
Correction of the initial angular deformities was achieved after the osteotomies,
and function was improved.
PMID- 9651773
TI - Patellofemoral contact forces and pressures during intramedullary tibial nailing.
AB - Patellofemoral joint forces and pressures were measured in a cadaver model during
intramedullary nailing of the tibia. A significant increase in contact pressures
was found at the lateral facet of the patellofemoral articulation using the
medial paratendinous approach (P = 0.01) and at the medial facet when using the
trans-patellar tendon approach (P = 0.001) to the proximal tibia. Increased
contact pressures at the patello-femoral joint may result in chondral injury,
which in turn may cause anterior knee pain, a common complication of tibial
nailing.
PMID- 9651774
TI - Unreamed intramedullary locking nailing for open tibial fractures.
AB - We reviewed the results of the treatment of 24 cases of open tibial fractures
using unreamed intramedullary locking nailing. The fractures were classified,
following the Gustilo system as grade I-7, grade II-7 and grade III-10. The
average time to achieve bony union was 22 weeks with a 26% incidence of
pseudoarthrosis. There were no cases of deep infection. Five cases healed with
shortening of over 1 cm, but we did not observe angular deformity in any of the
patients. In 2 fractures with associated articular lesions, joint motion was
limited at final follow up. The nail broke in 2 cases and the screws in 5. The
surgical procedure is well tolerated by patients, allows good management of soft
tissue lesions and rehabilitation with low rate of infection and malunion. The
main disadvantages have been the relative high incidence of nonunion and breakage
of metal.
PMID- 9651775
TI - The posterior interosseous nerve and the radial tunnel syndrome: an anatomical
study.
AB - Twenty anatomical specimens were carefully studied in order to establish a
possible connection between the posterior interosseous nerve and the radial
tunnel syndrome. Our results show that the posterior interosseous nerve distal to
the supinator muscle may be compressed by various structures. These include the
distal border of the supinator muscle, the ramifications of the anterior and
posterior interosseous vessels, and the septum between the extensor carpi ulnaris
and the extensor digitorum minimi. The posterior interosseous nerve is also
stressed during passive supination (elongation and rotation), and during passive
pronation (compression). This suggests that the interosseous nerve distal to the
supinator muscle should be explored in radial tunnel compression syndromes.
PMID- 9651776
TI - The value of an operating microscope in peripheral nerve repair. An experimental
study using a rat model of tibial nerve grafting.
AB - The aim of this study was to test the hypothesis that the use of an operating
microscope improves the results of peripheral nerve repair. Tibial nerve grafting
was carried out on 48 Fischer rats divided into 2 groups: in one, a loupe was
used, and in the other a surgical microscope. At 5 months after grafting,
recovery was evaluated by functional, electromyographic, and morphometric tests.
The mean motor nerve conduction velocity was 26.77 +/- 9.37 m/sec in the group
where the loupe was used compared with 44.19 +/- 11.36 m/s when the microscope
group was used. The soleus muscle weight and the diameter of myelinated fibres
also confirmed better regeneration in the microscope group. These results clearly
indicate that it is essential to use the microscope for peripheral nerve repair.
PMID- 9651777
TI - Evaluation of simplified Frykman and AO classifications of fractures of the
distal radius. Assessment of interobserver and intraobserver agreement.
AB - In order to evaluate interobserver and intraobserver agreement of the Frykman and
AO classifications and their variations between assessors with different levels
of experience, three hand specialists, a fellow and two senior residents
classified radiographs of 200 fractures of the distal radius in anteroposterior
and lateral views. Reproducibility was assessed by the use of the proportion of
agreement and kappa coefficient between pairs of observers. The Frykman
classification showed moderate interobserver reproducibility (kappa = 0.43) and
good intraobserver reproducibility (kappa = 0.61). The experience of the
reviewers did not significantly affect either of these. The AO system showed
regular interobserver reproducibility (kappa = 0.37) and moderate intraobserver
reproducibility (kappa = 0.57). The younger group obtained higher intraobserver
agreement than the senior. Possible causes for the low reproducibility of both
classifications are discussed together with a review of the literature. We do not
recommend the Frykman or AO classifications for clinical application because of
their questionable reproducibility.
PMID- 9651778
TI - Simulation by stereographic processing of computed tomography for
transtrochanteric rotation osteotomy in necrosis of the femoral head.
AB - The transtrochanteric rotation osteotomy described by Sugioka will preserve the
femoral head in patients with avascular necrosis of the femoral head, but there
is controversy about the clinical results. We developed a simulation system for
rotation osteotomy, based on stereographic processing through computed
tomography, the object being to determine the indication for this procedure and
the degree of rotation required. This method makes it possible to determine the
degree of rotation needed to displace the necrotic areas from the weightbearing
zone; the need for a varus osteotomy can also be assessed. Our clinical results
improved when we used this method. CT stereographic drawings in patients with
avascular necrosis of the femoral head are useful for assessing the necrotic
area.
PMID- 9651779
TI - Rotationplasty as a limb salvage procedure for malignant bone tumours.
AB - Sixteen patients with malignant bone tumours, 15 osteosarcoma and one Ewing's
sarcoma, were treated by rotationplasty at Tata Memorial Hospital between 1989
and 1994. The functional results are better than after amputation.
PMID- 9651780
TI - External fixation in tumour pathology.
AB - An appraisal of the clinical records of patients with malignant bone tumours
enabled us to identify 61 whom we have treated by external fixation. There were
38 males and 23 females with ages ranging from 4 to 58 years, the mean being 14
years. The average period of follow-up was 6 years (1-12 years). For the purpose
of our analysis the patients were divided into three groups according to whether
the fixator was fitted before, during or after tumour resection.
PMID- 9651781
TI - Skeletal metastases of intermediate grade chondrosarcoma without pulmonary
involvement. A case report.
AB - Although pulmonary metastases are typical of chondrosarcoma, only 2 patients with
intermediate grade tumours have been reported with bone metastases and without
pulmonary involvement. We report one patient with an intermediate grade
chondrosarcoma which metastasised to the lumbar spine following surgical
resection of a locally recurrent tumour. The local recurrence and the metastases
were resected and she is alive and well after 20 months.
PMID- 9651782
TI - Simple bone cysts treated with aspiration and a single bone marrow injection. A
preliminary report.
AB - The results of a single percutaneous aspiration and injection of marrow into
active, simple bone cysts are reported in 8 cases. Slow regression of the cyst
was consistently observed except in one lesion in the distal tibia. All the
patients have been free of symptoms after this treatment after a mean follow up
of 31 months. The evolution of the cysts was monitored by a cyst index, cyst
diameter measurements and computer assisted densitometric image analysis of
serial radiographs.
PMID- 9651783
TI - Congenital insensitivity to pain with anhidrosis. A case report.
AB - We present a five-year-old girl with congenital insensitivity to pain with
anhidrosis. A skeletal radiographic survey revealed several old fractures.
Application of pilocarpine showed anhidrosis and nerve biopsy revealed a
significant decrease in the number of myelinated and unmyelinated nerve fibres.
PMID- 9651784
TI - Structural bases of Fc gamma R functions.
AB - This review describes structures which determine the biological activities
triggered by Fc gamma R and account for the cell-mediated functions of IgG
antibodies in physiology and pathology. The binding specificity and affinity of
Fc gamma R depend primarily on IgG-binding structures, in their immunoglobulin
like extracellular domains. Binding is however also influenced by subunits that
associate to multichain Fc gamma R. Effector and regulatory intracytoplasmic
sequences that are unique to molecules of the Fc gamma RIIB family determine the
internalization properties of these receptors. Immunoreceptor Tyrosine-based
Activation Motifs (ITAMs) are intracytoplasmic effector sequences shared by Fc
gamma R and other receptors involved in the recognition of antigen, which trigger
cell activation and internalization. Immunoreceptor Tyrosine-based Inhibition
Motifs (ITIMs) are intracytoplasmic sequences, shared by Fc gamma RIIB and a
growing number of negative coreceptors which negatively regulate cell activation
via ITAM-bearing receptors. Altogether, these structures enable IgG antibodies to
exert a variety of finely tuned biological effects during the immune response.
PMID- 9651785
TI - Human IgG Fc receptors.
AB - Human IgG receptors constitute a family of glycoprotein complexes consisting of
ligand-binding, and associated signaling chains. Three leukocyte classes (Fc
gamma RI, II, and III) and one separate endothelial Fc gamma R class (FcRB) are
defined which are expressed on hematopoietic and endothelial cells. Upon
interaction with IgG, Fc gamma R initiate a plethora of signaling cascades
involving receptor signaling motifs, and protein tyrosine kinases and
phosphatases. These cascades ultimately culminate in activation or deactivation
of effector cells, resulting in initiation or down-modulation of cellular
processes. Recent evidence points to a crucial in vivo role of Fc gamma R in both
initiation and regulation of inflammatory and cytotoxic responses. These Fc gamma
R-mediated immune responses can be exploited to develop novel immunotherapies.
PMID- 9651786
TI - IgG binding sites on human Fc gamma receptors.
AB - The structure for the three human Fc gamma receptors classes Fc gamma RI (CD64),
Fc gamma RII (CD32) and Fc gamma RIII (CD16) has been well characterized. Here
the IgG binding sites on Fc gamma RII and Fc gamma RII with their responsive FG,
BC and C'/E loops on the membrane proximal domains are described in detail. For
Fc gamma RI the second extracellular domain is suggested as a key structure of
IgG binding. The lower hinge regions of human and murine IgG binding to these Fc
receptors and their structural relationship in Fc gamma R-IgG interactions are
discussed. The potential of inhibiting the pathophysiological effects of Fc gamma
receptors by blocking studies are considered for future therapeutic modalities.
PMID- 9651787
TI - Soluble Fc gamma receptors: interaction with ligands and biological consequences.
AB - Soluble Fc gamma receptors are produced by cleavage of the membrane receptors or
by alternative splicing. They are found in biologic fluids. After a brief
description of the structure and mode of production of soluble Fc gamma R, we
address the question of ligands and function of the soluble Fc gamma R by using
recombinant molecules and transgenic animals. We show that soluble Fc gamma R are
not only IgG-binding factors which interfere with, and block, Fc-dependent immune
reactions but also molecules that interact, in vitro, with non-Ig-ligands such as
CR3 and CR4 and are trigger or regulate immune functions via these receptors.
PMID- 9651788
TI - Structure and functions of CD23.
AB - This review summarizes recent data on CD23, a low affinity receptor for IgE (Fc
epsilon RII). CD23 is the only FcR which does not belong to the immunoglobulin
gene superfamily. The CD23 molecule was discovered independently as an IgE
receptor on human lymphoblastoid B cells [1], as a cell surface marker expressed
on Epstein-Barr-Virus-transformed B cells (EBVCS) [2] and as a B-cell activation
antigen (Blast 2) [3]. CD23 was shown to be a low affinity receptor for IgE
[4,5]. Similar to most FcR, soluble forms of CD23 (sCD23) are released into
extracellular fluids. The soluble fragments formed by proteolytic cleavage of
surface CD23 are not only capable of binding IgE (IgE binding factors) but also
exhibit multiple functions that are not IgE related. These observations together
with the finding that CD23 displays significant homology with Ca(2+)-dependent (C
type) animal lectins, suggested the existence of natural ligands other than IgE.
The recent finding that CD23 interacts with CD21, CD11b and CD11c indicates that
CD23 should be viewed not only as a low affinity IgE receptor but also as an
adhesion molecule involved in cell-cell interaction. After a brief overview of
the molecular structure, there follows a discussion of the biological activities
ascribed to human CD23.
PMID- 9651789
TI - CD23/Fc epsilon RII: signaling and clinical implication.
AB - CD23 is an activation antigen expressed by various human hematopoietic cells,
tissular epithelial cells and represents the major low affinity receptor for IgE
(Fc epsilon RII). In its membrane and soluble forms, CD23 has multiple ligands
that enable this molecule to trigger various functions in human and murine cells.
In this issue, we discussed the intracellular signaling events induced by soluble
CD23 and the ligand involved in each target cell. Signal transduction through
surface CD23 ligation is linked to cyclic nucleotides and nitric oxide (NO)
pathways in various human cells and in rat macrophages. Recent in vivo data
suggest a regulatory role for these signals during various human
physiopathological situations such as hemopoiesis, anti-tumoral defense,
inflammation, allergy, microbicidal activity of macrophages and eosinophils, skin
disease, and HIV infection.
PMID- 9651790
TI - Fc receptors as targets for immunotherapy.
AB - Human membrane and soluble Fc epsilon receptors (Fc epsilon RI, Fc epsilon
RII/CD23) and Fc gamma receptors (Fc gamma RI/CD64, Fc gamma RII/CD32, Fc gamma
RIII/CD16) have been implicated in a number of diseases. Their functional roles
such as capture and clearance of immune complexes, antibody-dependent cell
cytotoxicity, or cytokine or inflammatory mediator release, make them potential
targets for immuno-intervention. In the present review, we will describe how
membrane and soluble human Fc epsilon R and Fc gamma R have been already used as
targets/tools for immuno-interventions by using monoclonal and bispecific
engineered antibodies. Some therapeutic uses of these molecules both in cancer,
infectious, and auto-immune diseases are presented.
PMID- 9651791
TI - Functions of Fc receptors on human dendritic Langerhans cells.
AB - Immature dendritic cells are antigen presenting cells highly specialized for
capturing and processing foreign protein antigens. These cells express Fc gamma
RII and Fc epsilon RI which, by their ability to internalize and use the
endocytic pathway, increase their capacity to process antigens. Immature
dendritic cells, such as epidermal Langerhans cells, also release soluble forms
of Fc gamma RII. These latter molecules are likely to compete with the membrane
associated Fc gamma R to diminish or abrogate the capacity of dendritic cells to
present immune complexes, as suggested by our in vitro experiments using both
human and mouse epidermal Langerhans cells. However, when dendritic cells mature
in vitro and become efficient stimulators of resting T cells, they rapidly down
regulate and sometimes completely abolish the expression of their membrane
associated Fc gamma R and Fc epsilon RI. Consequently, they lose or at least
strongly diminish their capacity to capture immune complexes. At this stage, the
release of soluble Fc gamma R by dendritic cells is also markedly diminished. One
can hypothesize that the membrane-associated Fc gamma RII and the soluble Fc
gamma RII are molecules expressed when dendritic cells are potent capturing and
processing cells, the soluble Fc gamma RII molecule acting by competition as a
negative regulatory element on the Fc gamma RII-mediated internalization of IgG
containing immune complexes. Thus, the expression of membrane-associated Fc gamma
R and Fc epsilon RI, as well as the release of soluble Fc gamma R, would seem to
characterize the immature stage of dendritic cells.
PMID- 9651792
TI - What health professionals can do to identify and resolve patient dissatisfaction.
AB - BACKGROUND: Patient satisfaction affects consistency of self-care, health
outcomes, level of service utilization, choice of health professionals, and
decisions to sue in the face of adverse outcomes. Understanding patients'
specific dissatisfactions may help health professionals and administrators
identify and rectify organizational deficiencies before they become costly.
COMMON CAUSES OF COMPLAINTS: As part of a series of research projects, more than
12,000 patient/family complaint narratives were examined in which patients or
patients' family members told interviewers or patient advocates about the care
they received from their health professionals in both inpatient and outpatient
settings. Complaints may be categorized as involving issues of care and
treatment, communication, humaneness, access and availability, environment, and
billing/payment. STRATEGIES FOR RESOLVING COMPLAINTS: Even though caregivers may
not have control over all the factors that lead to dissatisfaction, they can
often hear and address complaints. As a result, they may not only contribute to
quality of care but improve the systems in which they practice. The challenges
are how to prevent dissatisfaction in the first place, and, if it does occur, to
identify and if possible rectify patient concerns. Three case studies are
provided. CONCLUSION: All health professionals must be involved in efforts to
resolve problems that compromise patient care. Some problems could be prevented
if administrators and leaders used complaint data to recommend new policies and
procedures or to identify and counsel with health care team members who generate
disproportionate numbers of complaints. If all are involved in both prevention
and problem solving, resources devoted to uncovering, understanding, and
resolving patient complaints are likely to prove cost-effective.
PMID- 9651793
TI - Using a hospitalwide performance improvement process for patient education
documentation.
AB - BACKGROUND: Decreases in length of hospital stay have increased pressure on staff
to provide appropriate patient education. A hospitalwide continuous quality
improvement (CQI) program was implemented to improve patient education
documentation at Raritan Bay Medical Center (RBMC; Perth Amboy, NJ). IMPROVING
THE PATIENT EDUCATION DOCUMENTATION PROCESS: In March 1995 the patient education
committee was given the responsibility to develop a CQI program to improve
documentation of patient education. Patient interviews revealed that assessment
of patients' initial knowledge was inadequate and goal setting was omitted. The
committee developed generic and disease-specific patient education documentation
forms for educational assessment and patient education. The patient chart was
reconfigured to include a central location for patient education. RESULTS: A
review of almost 900 patient records established that the percentage of records
on which patient education was documented had improved from 41% in summer 1995 to
93% in fall 1996, with an improvement across all disciplines. A follow-up review
in fall 1997 of 136 randomly chosen records indicated a slight decrease in rate
of documentation of content areas, although nursing services and nutritional care
continued to maintain their patient documentation education at a rate of > or =
90%. DISCUSSION: Factors such as providing continuous feedback on patient
education documentation performance to all nursing units and disciplines
involved, developing additional disease-specific education assessment
plans/documentation tools through an interdisciplinary process, and improving the
data collection tool after each measurement period all contributed to improved
patient education documentation. CONCLUSIONS: Patient education is now truly
integrated at RBMC, with every pertinent discipline involved in decision making
throughout the process of continuously improving the patient education process
and documentation.
PMID- 9651794
TI - The "door-to-needle blitz" in acute myocardial infarction: the impact of a CQI
project.
AB - BACKGROUND: A continuous quality improvement (CQI) project was conducted at
Soroka Medical Center in Beer-Sheva, Israel, in an effort to identify and address
causes of delays in thrombolytic therapy in patients arriving at a high-volume
(160,000 patients per year) emergency department with acute myocardial infarction
and thereby reduce the "door-to-needle time" (DTNT). The study had four phases:
preintervention survey, peri-intervention process redesign, postintervention
evaluation, and follow-up evaluation. CQI TEAM: The CQI team followed a seven
step protocol: problem definition, present-state screening, factors analysis,
solution development, outcome evaluation, standardization, and conclusions.
RESULTS: A DTNT of 45 minutes was considered acceptable for this data set, and
accordingly, patients were divided into an "early" group (n = 50, DTNT < 45
minutes), and a "late" group (n = 50, DTNT > or = 45 minutes). After the CQI
intervention, the mean DTNT decreased from 61.8 +/- 32.5 (mean +/- standard
deviation) to 47.6 +/- 18.5 minutes (p < 0.029). The prolonged DTNT time
intervals of the late versus the early groups was primarily due to extended
decision-making time (36.0 +/- 22.7 versus 13.6 +/- 6.7 minutes, p < 0.003),
followed by time until therapy was initiated (26.2 +/- 14.2 versus 11.1 +/- 5.8
minutes, p < 0.002). CONCLUSIONS: Results suggest that the 30-minute DTNT
suggested by the American College of Cardiology/American Heart Association is
appropriate for patients with a clear diagnosis and no contraindications for
thrombolysis, but when the risk-benefit ratio of thrombolytic therapy raises
concerns, a 45- to 60-minute DTNT may still be acceptable. Further CQI projects
should address technical triage of simple cases and clinical estimation of risk
benefit ratio in complicated patients.
PMID- 9651795
TI - Long-term follow-up in the Peer Assessment Program for nonspecialist physicians
in Ontario, Canada.
AB - BACKGROUND: The College of Physicians and Surgeons of Ontario has assessed
randomly selected physician office practices since 1972. Each assessment consists
of a tour of the premises and a review of a random selection of 20 to 30 medical
records to evaluate the system of record keeping and the content of the records
and to thereby indicate the quality of the physician's examinations, history
taking, diagnosis and management plan. About 12% of nonspecialist physicians who
need help to improve their records and/or the care they provide are identified
annually, and following an interview with peers and simple educational
interventions, more than 75% are successful in improving. METHODS: A follow-up
was conducted to assess physician practices an average of six years after the
first intervention. The reviewers were blinded as to whether the physician being
reviewed had been reviewed previously. Each revisited physician was matched to
three others undergoing their initial assessments in the same year. The matching
variables were age, sex, school of graduation (Canadian versus other), rural
versus urban practice location, and affiliation status with the College of Family
Physicians of Canada. The assessed performance of the two groups was compared.
RESULTS: The performance of the revisit group was significantly better than that
of the matched group (p = 0.05). CONCLUSIONS: The assessment, interview, and
educational interventions undertaken by the licensing authority produced an
improvement in practice in the short term in the bottom 10%-15% of all physicians
reviewed, which was sustained for more than six years.
PMID- 9651796
TI - Insulin decreases skeletal muscle cAMP-dependent protein kinase (PKA) activity in
normal monkeys and increases PKA activity in insulin-resistant rhesus monkeys.
AB - Insulin activation of skeletal muscle glycogen synthase and glucose disposal is
defective in both prediabetic and diabetic primates. Reduction in the activation
of glycogen synthase by insulin could be the cause of lower glucose disposal
rates, and could be the result, at least in part, of the failure of insulin to
inhibit cAMP-dependent protein kinase activity (protein kinase A, PKA). To
examine this proposed mechanism, PKA activity was measured in skeletal muscle
(vastus lateralis) samples freeze-clamped in situ under basal fasting conditions
before, and again during a euglycemic hyperinsulinemic clamp in 27 rhesus
monkeys. Nine of the monkeys were normal (normal fasting glucose and insulin),
eight were prediabetic (normal fasting glucose and hyperinsulinemia) and ten had
spontaneous non-insulin-dependent diabetes (hyperglycemia). Insulin lowered PKA
activity ratio in normal monkeys (basal vs insulin-stimulated, 14.4 +/- 3.2 vs
8.1 +/- 1.8%, p < 0.05), but raised PKA activity ratio in prediabetic monkeys
(5.4 +/- 1.4 vs 10.5 +/- 2.6%, p < 0.05). PKA activity ratio was unaffected by
insulin in the diabetic monkeys (6.7 +/- 1.8 vs 7.5 +/- 1.4%). Basal PKA activity
ratio was higher in normal monkeys compared to prediabetic (p < 0.05) and
diabetic monkeys (p < 0.05). Basal PKA activity ratio was inversely related to
the insulin-stimulated change in PKA activity ratio (r = -0.72, p < 0.001). We
conclude that in vivo insulin during euglycemic hyperinsulinemic clamp decreases
skeletal muscle PKA activity ratio in normal monkeys but fails to decrease the
activity ratio of PKA in insulin resistant (prediabetic and diabetic) monkeys.
The insulin resistant state is characterized by low basal fasting skeletal muscle
PKA activity ratio.
PMID- 9651797
TI - Temporal effect of methyl parathion on ovarian compensatory hypertrophy,
follicular dynamics and estrous cycle in hemicastrated albino rats.
AB - Methyl parathion, an organophosphorus pesticide, was administered i.p. at a dose
of 5 mg/kg body weight to hemicastrated virgin rats for 1, 5, 10 and 15 days.
Treatment with methyl parathion for 1 and 5 days revealed no change in the
ovarian weight with -0.64% and -9.63% hypertrophy respectively and no change in
healthy and atretic follicles when compared with hemicastrated oil-treated
controls. However, treatment with methyl parathion for 10 and 15 days resulted in
a significant decrease in ovarian weight gain with -21.36% and -31.98%
hypertrophy, respectively, a significant decrease in the number of healthy
follicles, and no change in the number of atretic follicles. The number of
estrous cycles and duration of each phase of the estrous cycle were significantly
affected with methyl parathion treatment for 5, 10 and 15 days. However, there
were no significant changes in the number of estrous cycles and duration of
estrus and metestrus phases in 1 day methyl parathion treatment except for a
decrease and increase in proestrus and diestrus phases respectively. The weight
of the uterus was significantly decreased whereas those of the liver, kidney and
adrenal did not change in any of the methyl parathion treated groups.
PMID- 9651798
TI - Rat aorta and mesenteric artery respond differently to serotonin.
AB - The sensitivity (EC50) of the ring segment of the mesenteric artery to serotonin
(4.84 +/- 0.53 x 10(-7) mol.l-1) was 17x greater than that of the aortic ring
segment (5.29 +/- 0.46 x 10(-6) mol.l-1). Incubation of the ring segments in
physiological salt solution (PSS) containing methylene blue greatly potentiated
the sensitivity of both the aorta and mesenteric artery to serotonin. The degree
of potentiation was higher in the aorta than mesenteric artery. L-NAME also
increased the sensitivity of both the aorta and mesenteric artery to serotonin
and there was no difference in the degree of potentiation of the responses
between the aorta and the mesenteric artery. Indomethacin inhibited the
contractile responses of the aorta and the mesenteric artery to serotonin.
Phenoxybenzamine reduced the contractile responses of both the aorta and the
mesenteric artery by the same magnitude. Captopril (10(-4) mol.l-1) significantly
attenuated the responses of the mesenteric artery more than the aorta, while
methysergide (10(-8) mol.l-1) completely abolished the difference in the
responses (EC50 for aorta = 3.50 +/- 0.55 x 10(-5) mol.l-1 vs 5.00 +/- 0.49 x 10(
5) mol.l-1 for mesenteric artery). This study demonstrates that rat aorta and
mesenteric artery respond differently to serotonin and the differential response
is due to a methylene blue sensitive factor and differences in either the
receptor population or sensitivity.
PMID- 9651799
TI - The effect of antioxidant vitamins E and C on lipoperoxidation of erythrocyte
membranes during hyperbaric oxygenation.
AB - The aim of this research was to determine whether administration of an
antioxidant vitamin combination can reduce oxidative damage in erythrocytes
induced by hyperbaric oxygenation (HBO). Malonyldialdehyde (MDA) levels and
osmotic fragility ratios in erythrocytes of 28 rats were compared in group A
[control], group B [Vitamin (E + C)], group C [HBO] and group D [HBO + Vitamin (E
+ C)]. HBO was applied at a pressure of 2.8 atmospheres absolute (ATA), 1 hour
daily, for 45 days in groups C and D. Administration of alpha-tocopherol acetate
(40 mg/kg) and Na-ascorbate (200 mg/kg) was initiated 3 days before the start of
HBO exposures and administered intraperitoneally 3 times a week for 45 days. MDA
levels and osmotic fragility ratios were significantly higher in group C than in
groups A and B (p < 0.05 for all). Significant decreases in MDA levels and
osmotic fragility were observed in group D compared with group C, although these
parameters were still significantly higher than in controls (p < 0.05 for all).
Prolonged HBO resulted in oxidative damage indicated by significant increases in
MDA levels and osmotic fragility ratios, which were reduced by concomitant
vitamin (E + C) administration.
PMID- 9651800
TI - Effect of chloroquine on the contractility of the smooth muscles of the rat
uterus, trachea and urinary bladder.
AB - This study was performed to investigate the effect of chloroquine (CQ) on the
contractility of isolated smooth muscles of the rat uterus, urinary bladder; and
trachea. Chloroquine, 4 x 10(-4) mol.l-1 completely abolished uterine
contractions produced by 10(-2) IU/ml oxytocin, and 10(-6) mol.l-1 5
hydroxytryptamine (5-HT) and acetylcholine (Ach). Chloroquine also caused a
concentration-dependent relaxation of 10(-6) mol.l-1 Ach-contracted rat trachea.
Cumulative addition of CQ (10(-8)-10(-3) mol.l-1) to spontaneously contracting
rat urinary bladder did not produce any significant effect. It also did not
affect the contractile response of the bladder to Ach and 5-HT. The results
suggest that CQ inhibits the contractile process in the rat uterus and trachea
but not the urinary bladder.
PMID- 9651801
TI - On the mechanisms of adenosine induced pulmonary vasoconstriction in rats.
AB - The effect of adenosine on pulmonary vessels was studied in isolated perfused rat
lungs. Drugs were administered intra-arterially in a fixed volume of 0.1 ml Krebs
solution as bolus injections. Adenosine responses were obtained before and 10 min
after drug injections. When applied in logarithmically increasing doses (1-100
micrograms/ml), adenosine caused dose-dependent increases in pulmonary perfusion
pressure (e.g. pulmonary vasoconstriction) which were readily reversible.
Challenging adenosine with quinidine, dihydroergocristine and cyproheptadine (2
micrograms/ml each) did not significantly alter adenosine responses. Pretreatment
of lungs with 0.5 mM theophylline, 10 micrograms/ml indomethacin, 30
micrograms/ml tebokan (a PAF antagonist) or 1 microgram/ml methylene blue for 10
min, however, antagonized the vasoconstrictor effect of the drug significantly.
From these experiments, it was concluded that the mechanisms underlying the
pulmonary vasoconstrictor action of adenosine are complex, and that both types of
purinoceptors, prostaglandins, PAF and other vascular endothelial hormones might
be involved.
PMID- 9651802
TI - Neuron degeneration induced by verapamil and attenuated by EGb761.
AB - Calcium channel blockers are used as neuroprotective agents, as glutamate
antagonists. However, it has been found that calcium channel blockers may
compromise neuronal survival after long-term exposure. To explore the mechanisms
of the toxicity of calcium channel blockers on neurons, we studied the
morphological characteristics and biochemical changes of cultured cortical
neurons treated with verapamil, a calcium channel blocker. We now report that
cerebral cortical cultures exposed to verapamil for 48 h undergo neuronal
degeneration in both concentration-dependent and time-dependent fashion, possibly
partially through the activation of apoptosis. On the other hand, it was found
that Ginkgo biloba extract (EGb761) attenuated verapamil-induced neuronal injury,
suggesting the possibility of using verapamil combined with EGb761 clinically.
Furthermore, both B-50 immunoactivity (BIA) and the concentration of
intracellular calcium in single neurons ([Ca2+]i) decreased after a 48-h exposure
to verapamil, suggesting that the mechanisms of verapamil-induced degeneration
may be associated with the disruption of intracellular calcium homeostasis and
the inhibition of normal axonal elongation.
PMID- 9651803
TI - Pathological studies on camelpox lesions of the respiratory system in the United
Arab Emirates (UAE).
AB - Three dromedary camels (Camelus dromedarius), which died from generalized
camelpox with lesions in the respiratory system, were investigated.
Histopathological lesions in the lung consisted of small, sometimes confluent
foci of proliferated bronchial epithelium, necrosis and fibrosis. Orthopoxvirus
cameli was demonstrated in all three cases by transmission electron microscopy
and the virus was isolated from the lung and trachea on Dubca cells. It was
proved by restriction enzyme analysis of the viral DNA that the isolates were
identical. Immunohistochemical examination showed numerous poxvirus antigen
positive cells in the bronchial epithelia. Immunolabelled material was found in
bronchial epithelial cells with hydropic degeneration and in infiltrating
macrophages.
PMID- 9651804
TI - The pathogenesis of experimental neosporosis in pregnant sheep.
AB - Three groups of eight pregnant sheep were inoculated with tachyzoites of the NCl
isolate of Neospora caninum at 45 (group 1), 65 (group 2) or 90 (group 3) days'
gestation. A further six animals (group 4) served as controls. Fourteen of the
infected ewes developed a fever, which in two cases was biphasic. In six ewes in
group 1, the fetuses died and were resorbed, and in the other two the fetuses
were aborted. In group 2, one ewe resorbed her fetus, six aborted dead fetuses
and one produced a live lamb. In group 3, six ewes aborted and two produced one
live and one stillborn lamb each. Thus, the stage of gestation influenced the
outcome of infection. All but one of the ewes "seroconverted", as shown by enzyme
linked immunosorbent assay, and 10 of 13 fetal sera examined by an indirect
immunofluorescent antibody test were positive. The polymerase chain reaction was
also used to detect DNA of N. caninum in aborted tissues. Immunohistochemical
examination showed that the parasite had invaded the placentas of all cases
examined, displaying an apparent predilection for fetal chorionic epithelium and
fetal placental blood vessels, as well as inducing thrombosis in some maternal
caruncular blood vessels. Organisms were associated with fetal vasculitis, focal
degeneration and inflammation of the chorioallantois, and widespread, severe
focal necrosis in the placentome. Characteristic lesions were seen in the fetal
brains, in addition to focal leucomalacia, thought to be due to anoxia resulting
from the placental damage. The six control sheep in group 4 remained clinically
healthy and produced normal uninfected lambs.
PMID- 9651805
TI - Morphometric analysis of bovine lymphomas classified according to the National
Cancer Institute Working Formulation.
AB - The National Cancer Institute Working Formulation (NCI-WF) for the subjective
classification of human non-Hodgkin's lymphoma is readily applicable to the
classification of bovine lymphomas. Forty-nine cases of bovine lymphoma were
analysed morphometrically to see if nuclear size and cleavage were distributed
continuously or discretely between different NCI-WF tumour cell types. The mean
nuclear area (+/- standard error of the mean, SE) was significantly greater (P <
10(-6)) in cells from the different types of diffuse large-cell lymphoma than in
cells from the different types of small-cell lymphoma (42.91 +/- 1.21 micron 2 vs
19.33 +/- 1.08 micron 2, respectively); there was no overlap between the two
groups. The mean nuclear are (+/- SE) of cells from diffuse large-cell lymphomas
was significantly greater (P < 10(-4)) than that of cells from small non-cleaved
lymphomas (42.74 +/- 1.72 micron 2 vs 27.54 +/- 1.08 micron 2, respectively), and
there was again no overlap between the two groups; these two cell types are
difficult to distinguish by any criteria other than size. Additionally, the cell
to-cell variability in nuclear area within a given tumour was significantly
greater (P < 0.001) for the diffuse large-cell type than for the small non
cleaved cell type. The mean nuclear form factor (+/- SE) and mean nuclear contour
indices (+/- SE) of the diffuse large cleaved cell type (0.53 +/- 0.02 and 5.08
+/- 0.11, respectively) were significantly different (P < 0.01 to 10(-6)) from
the same parameters in the diffuse large-cell type (0.82 +/- 0.01 and 3.94 +/-
0.04, respectively). Some of the major criteria of the NCI-WF used subjectively
to discriminate between bovine lymphoma cell types were supported by morphometric
measurements. The magnitude of the differences in nuclear morphological
characteristics between bovine lymphoma cell types was such that there was no
overlap.
PMID- 9651806
TI - Pasteurella multocida infection in the chicken embryo.
AB - Pasteurella multocida infection in embryonated chicken eggs was studied by chorio
allantoic membrane inoculation. Strain differences were demonstrated in terms of
lesion severity and time to death, especially during the first 24 h post
inoculation. A strain of low virulence gave a clear dose response but more
virulent strains did not. Comparable results were obtained by infecting 6-week
old chickens. The main lesions in inoculated embryos appeared as severe vascular
involvement of the entire embryo and feather tracts, thickening of the chorio
allantoic membrane, and enlargement and congestion of the yolk sac. The bacteria
were demonstrated by transmission electron microscopy, either extracellularly or
multiplying intracellularly in hepatocytes, heart tissue, and in the hyperplastic
layer of the chorio-allantoic membrane, with resulting damage to the cellular
organelles, and severe tissue changes.
PMID- 9651807
TI - Spontaneous tumours in tree shrews (Tupaia belangeri): population studies.
AB - In a necropsy series at the German Primate Centre, 63 of 1132 tree shrews were
found to have tumours. The youngest affected animal was < 6 months old, but the
incidence of tumours increased strikingly beyond 2 years of age; of 17 animals
aged > 8 years, no less than 14 (82.4%) were affected. The sites of neoplasia
were the genital system (22 cases), haematopoietic system (18 cases of malignant
lymphoma, many involving the digestive tract), lungs (14 cases), integument (five
cases), digestive tract (three cases other than those with malignant lymphoma)
and urinary bladder (one case).
PMID- 9651808
TI - Myocardial contraction band necrosis in stranded cetaceans.
AB - The term contraction band necrosis describes focal hypercontraction and lysis of
small groups of myocardial cells. Contraction band necrosis of the myocardium was
identified in 100% of 52 whales and dolphins (cetaceans) stranded along the
western coast of the Gulf of Mexico between April 1991 and November 1996. The
myocardial lesions in the cetaceans were identical, both grossly and
histologically, to those previously described in man and other animals. Such
lesions may contribute to the high mortality rate in stranded cetaceans.
PMID- 9651809
TI - Immunohistochemical demonstration of spread of Aujeszky's disease virus to the
porcine central nervous system after intestinal inoculation.
AB - Aujeszky's disease virus (ADV) was injected into the duodenal lumen of eight
specific pathogen-free pigs aged 5 weeks. The infected pigs did not show any
diarrhoea or nervous symptoms, but they developed characteristic necrotizing
enteritis and myenteric plexitis, accompanied by follicular necrosis in the
Peyer's patches. ADV antigen was detected in the submucosa of the dome area of
Peyer's patches, lymphatic follicles, Meissner's and Auerbach's plexuses, solar
ganglia and thoracic spinal ganglia. These findings suggest that ADV spreads from
the intestinal mucosa to the central nervous system via the autonomic nerves.
PMID- 9651810
TI - In-vitro studies on mechanisms of immunosuppression associated with bovine
respiratory syncytial virus.
AB - Bovine respiratory syncytial virus (BRSV) depressed the proliferative reactivity
of normal ovine peripheral blood lymphocytes to phytohaemagglutinin (PHA). This
BRSV-induced reduction in proliferative reactivity was not reversed or
ameliorated by the addition of (1) indomethacin or flunixin meglumine, substances
known to inhibit the production of prostaglandins, or (2) the cytokines,
interleukin-1 (IL-1) and interleukin-2 (IL-2), or (3) rat growth factor. The
results suggest that the suppression of ovine lymphocyte reactivity to PHA
associated with BRSV was not caused by the release of cyclooxygenase products
such as prostaglandins, or the production of inhibitors of IL-1 or IL-2.
PMID- 9651811
TI - The effects of bovine respiratory syncytial virus on the phagocytic and antigen
presenting capacity of peripheral blood monocytes and monocytic cell lines
derived from lambs and calves.
AB - Human respiratory syncytial virus and bovine respiratory syncytial virus (BRSV)
suppress lymphocyte responses to mitogens. In the present study, the possible
effects of BRSV on some functions of antigen-presenting cells (APC) were
investigated by exposing ovine monocytic cells to the virus before their use as
APC. The depletion of monocytes from peripheral blood mononuclear cells resulted
in the near total abrogation of proliferative responses to phytohaemagglutinin
(PHA). Reactivity was restored by the addition of homologous monocytic cells
derived from ovine peripheral blood monocytes as APC. The exposure of these
monocytic cells to BRSV for 48 h before their use as APC significantly reduced
the proliferative responses of uninfected ovine lymphocytes to PHA. Furthermore,
the exposure of bovine peripheral blood monocytes and bovine and ovine monocytic
cell lines to BRSV for 48 h reduced their capacity to phagocytize latex beads.
PMID- 9651812
TI - The carriage of Pasteurella haemolytica in sheep and its transfer between ewes
and lambs in relation to mastitis.
AB - The possible presence of Pasteurella haemolytica in the mouth of lambs and on the
skin of the teats of ewes was investigated. The organism was found in the mouth
of ewes and lambs and, soon after lambing, on the teat skin of ewes. It was not
isolated from the teat skin of pregnant ewes 1-14 days before lambing or from the
teat skin one week after the lambs had been weaned. The transfer of P.
haemolytica to the teat skin is undoubtedly mediated by the lamb. There is ample
opportunity for the teat orifice to be exposed to P. haemolytica during the
suckling period and it is known that only a few colony-forming units of virulent
organisms are required to initiate mastitis.
PMID- 9651813
TI - Evaluation of day-old specific pathogen-free chicks as an experimental model for
pathogenicity testing of intestinal spirochaete species.
AB - Specific pathogen-free chicks aged 1 day were challenged per os with strains of
five different species of intestinal spirochaete originally isolated from pigs or
human beings. A virulent strain of Serpulina hyodysenteriae (WA 15) colonized
chicks, causing retarded growth rate and histological changes, including caecal
atrophy, epithelial and goblet cell hyperplasia, and crypt elongation. A further
strain of S. hyodysenteriae (SA3), which was apparently avirulent for pigs, and a
strain of Serpulina intermedia (889) colonized fewer chicks, caused less severe
lesions and did not significantly depress growth rate. Strains of Serpulina
murdochii and Brachyspira aalborgi failed to colonize or cause histological
changes. Four strains of Serpulina pilosicoli (Kar, Rosie-2299 and GAP 401,
isolated from human beings, and 3295, isolated from a pig) colonized chicks, and
large numbers showed polar attachment to the caecal epithelium; all strains,
apart from Rosie-2299, caused watery diarrhoea and wet litter, but did not
significantly retard growth. Variation both in the degree of spirochaetal
attachment and the resulting development of lesions was observed between S.
pilosicoli strains as well as between individual chicks infected with the same
strain. The study indicated that chicks may be useful in studying the
pathogenicity of strains of S. hyodysenteriae, S. intermedia and S. pilosicoli.
PMID- 9651814
TI - Effects of nicotine on peripheral cutaneous blood flow and skin temperature.
AB - We hypothesized that if nicotine was used in a form that was not adulterated with
other hazardous substances found in tobacco, it would increase cutaneous blood
flow (CBF) resulting in an increase in skin temperature. The effects of nicotine
on CBF was investigated in 80 healthy volunteers and 6 patients with peripheral
circulation disturbances. Each subject was required to chew nicotine gum
(containing 2 mg nicotine) for 15 min and the CBF was then measured with laser
blood flowmetry. Skin temperature of 35 volunteers was measured with thermography
before and after chewing the gum for 15 min. A control study was performed using
ordinary gum without nicotine. Increased CBF (> or = + 1 ml/min/100 g) was
observed in 55 of 86 subjects (64%, 33.7-38.6 ml/min/100 g, P < 0.01). An
elevation in skin temperature (> + 0.1 degree C) was also observed with nicotine
gum in 26 of 35 healthy subjects (74%, + 0.62 +/- 0.96 degree C, P < 0.001). The
increase in CBF was greater in subjects in which the initial CBF was lower than
in others (P < 0.01). Nicotine gum was found to increase CBF (55/86) and elevate
skin temperature (26/35). The smaller the initial CBF value, the greater was the
increase in CBF. Nicotine or nicotine derivatives might prove to be useful agents
for the treatment of peripheral circulation disturbances.
PMID- 9651815
TI - Analysis of mechanisms of epidermal proliferation induced by intracutaneous
injection of cholera toxin by the use of site-specifically mutated cholera
toxins.
AB - Intracutaneous injection of cholera toxin (CT) into rabbits increases vascular
permeability and induces epidermal proliferation. To understand the mechanisms of
these effects on the skin, we evaluated the involvement of the ADP
ribosyltransferase activity of the A subunit of CT and receptor-binding
interactions between GM1-ganglioside and the B subunit of CT. We constructed two
mutant CTs, E112K and W88K, by site-directed mutagenesis. Mutant CT-E112K, in
which glutamic acid at position 112 (E112) of the A subunit of CT was replaced by
lysine, has been shown to have lost its biological activity on Chinese hamster
ovary (CHO) cells because of its abolished ADP-ribosyltransferase activity.
Mutant CT-W88K, in which tryptophan at position 88 (W88) of the B subunit of CT
was replaced by lysine, has been shown to have lost its binding ability to GM1
ganglioside. Intracutaneous injection of these mutant CTs evoked less vascular
permeability and less epidermal proliferation than recombinant wild-type CT.
These results suggest that: (1) the ADP-ribosyltransferase activity carried by
E112 of the A subunit of CT; and (2) the binding ability to GM1-ganglioside via
W88 of the B subunit of CT are essential for these effects of CT on the skin.
PMID- 9651816
TI - Interferon-gamma-dependent induction of manganese superoxide dismutase activity
of SV40-transformed human keratinocytes by anti-Fas antibody and by TNF-alpha.
AB - It has been reported that cellular oxidative stress induces apoptosis, that may
be inhibited by scavengers of reactive oxygen intermediates (ROIs). Superoxide
dismutase (SOD) is among the most active scavengers of ROIs, providing defense
against the cellular oxidative stress. Fas antigen and tumor necrosis factor
(TNF) receptor are the cell surface proteins, stimulation of which induces
apoptosis of keratinocytes. Using SV40-transformed human keratinocytes (SVHK
cells), we investigated the effects of anti-Fas antibody and TNF-alpha on the SOD
activity. Treatment of SVHK cells with anti-Fas antibody or TNF-alpha in the
presence of interferon-gamma (IFN-gamma) resulted in an increase in Mn-SOD
activity, Cu,Zn-SOD activity was not affected. In the absence of IFN-gamma, no
increase in Mn-SOD activity was detected. The induction of IFN-gamma-dependent Mn
SOD activity by anti-Fas antibody or TNF-alpha was concentration-dependent; the
maximal effect was observed at 1-10 micrograms/ml and 5-10 ng/ml, respectively.
The increase in Mn-SOD activity was observed at 6 h following the treatment and
remained for at least 48 h. Northern blot analyses showed that Mn-SOD mRNA
increased within 3 h without a significant change in Cu,Zn-SOD mRNA. The addition
of both anti-Fas antibody and TNF-alpha in the presence of IFN-gamma resulted in
an additive increase in Mn-SOD activity. Although the addition of 12-o
tetradecanoylphorbol-13-acetate (TPA) singly to the incubation medium had no
effect on either Mn-, or Cu,Zn-SOD activity, it significantly augmented the IFN
gamma-dependent induction of Mn-SOD activity by anti-Fas antibody or by TNF
alpha. The protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl
piperazine dihydrochloride (H-7), significantly inhibited the TPA-dependent
increase in Mn-SOD activity. These results indicate that the stimulation of Fas
antigen or TNF receptor increases Mn-SOD activity of SVHK cells in the presence
of IFN-gamma and that TPA augments the process through the activation of protein
kinase C.
PMID- 9651817
TI - Morphological, biochemical and molecular biological characteristics of a
granulocyte colony-stimulating factor-producing human eccrine carcinoma cell
line.
AB - We describe here a newly established cell line from an eccrine carcinoma which
produced an abundant amount of granulocyte colony-stimulating factor (G-CSF). An
eccrine carcinoma of the scalp of a 69 year-old-Japanese female had metastasized
to the pleura. Clinically, she had marked neutrophilia (up to 60,000/mm3), and a
high level of G-CSF (38.7 x 10(3) pg/ml) was detected in the pleural effusion, as
determined by enzyme-linked immunosorbent assay (ELISA). We established a cell
line in vitro and maintained the cells in culture for 30 months in 90
subcultures. We investigated whether these tumor cells were able to produce G-CSF
in culture and found that they were. We also found that the amount of G-CSF
produced paralleled the rise in cell number (26.5 x 10(3) pg/ml at confluency).
When culture media were administered to rabbits (25 ml/rabbit), the amount of
circulating neutrophils increased until the number was equal to or greater than
that resulting from injection of recombinant human G-CSF (rhG-CSF)(75
micrograms). This effect persisted for 7 days. When tumors were induced in SCID
and nude mice by injecting cultured cells (1 x 10(7) cells/mouse), the number of
circulating neutrophils also correlated well with tumor size in these mice
(200,000/mm3, 3 cm tumor). After tumor removal, the neutrophil number returned to
normal within 30 days. G-CSFmRNA in cultured, cells was detected by RT-PCR. Based
on these results, it was confirmed that the marked neutrophilia observed in the
patient was caused by the tumor-generated G-CSF. This is the first G-CSF
producing cell line developed from a cancer of the skin.
PMID- 9651818
TI - Further characterization of a new in vitro angiogenesis model under serum free
culture conditions; suppression of endothelial cell differentiation by serum.
AB - We studied the regulation of the extracellular matrix in the recently established
murine vascular endothelial cell clones, F-2 or F-2C. F-2 cells constitutively
show a cobblestone growth pattern under serum supplemented culture conditions,
whereas F-2C cells undergo spontaneous histodifferentiation to form tubular
structures in chemically defined media. We reported that the tubulogenesis
induced by F-2C might relate to the heavy deposition of a 'basement membrane
analog' as a subendothelial matrix (SEM). We further characterized the regulation
of extracellular matrix (ECM) metabolism in these cell clones, in terms of
gelatinase expression, ECM degradation and the effects of serum. F-2C cells in
culture medium containing 1% serum did not undergo tubulogenesis but presented
cobblestone growth. Zymography analysis showed that both F-2 and F-2C cells
express two gelatinase (72 and 92 kDa). However, F-2 cells mainly expressed the
former and faintly the latter, whereas F-2C mainly expressed the latter.
Proteolysis studies showed that the spent media conditioned by F-2C cells
partially cleaved type IV collagen and completely degraded type V collagen. The
cleavage of type V collagen was suppressed by the addition of serum, whereas that
of type IV collagen was not. The proteolysis of laminin and fibronectin by the
conditioned medium was not observed. Serum-supplemented F-2 or F-2C cultures
markedly suppressed SEM deposition. These results indicated that F-2C cells under
serum free culture conditions not only present a simple and useful in vitro model
with which to study the dynamic processes of proteolysis and ECM metabolism
during the sequential phases of angiogenesis, but is also useful for analyzing
the serum effects on angiogenesis (AG).
PMID- 9651819
TI - Effects of various salts and irradiation with UV light on the attachment of
Staphylococcus aureus strains.
AB - We investigated the attachment of Staphylococcus aureus isolated from atopic
dermatitis lesions to plastic tissue-culture coverslips. We found that attachment
was weaker in (rabbit) plasma with 5 or 10% NaCl and in plasma with 5 or 10% sea
salts than in the control plasma after incubation for 2 h (P < 0.01). The
attachment was weaker still in plasma with 10% NaCl or 10% sea salts than in the
control plasma after incubation for 24 h (P < 0.01). Plasma coagulation of four
S. aureus strains isolated from atopic dermatitis lesions was not detected in
plasma with 10% NaCl (pH 5.6) or 10% sea salts (containing 0.372% Mg2+) after
incubation for 12, 24, 36 and 60 h. The attachment of S. aureus strain cells to
the coverslip in plasma was weaker after irradiation with UVA at 25 or 50 J/cm2
(P < 0.01) and UVB at 0.5 J/cm2 (P < 0.05) both of which are covered by a black
cloth, than without irradiation after incubation for 24 h. Plasma coagulation was
not detected after irradiation with UVA at 25 or 50 J/cm2 with a black cloth
cover (temperature reached 50 degrees C), but was detected after UVA irradiation
at the same doses combined with cooling (temperature reached 22 degrees C), after
incubation for 24 h. The results suggest that the attachment of S. aureus cells
isolated from atopic dermatitis lesions to the coverslip is suppressed in the
presence of 10% salts and irradiation with UVA and UVB, and that plasma
coagulation of S. aureus cells isolated from atopic dermatitis lesions is
suppressed in the presence of 10% salts, irradiation with UVA, and heating.
PMID- 9651820
TI - Modulation of UVA light-induced oxidative stress by beta-carotene, lutein and
astaxanthin in cultured fibroblasts.
AB - The ability of beta-carotene, lutein or astaxanthin to protect against UVA
induced oxidative stress in rat kidney fibroblasts (NRK) was assessed. Activities
of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), and
changes in thiobarbituric acid reactive substances (TBARS) were measured as
indices of oxidative stress. Exposure to UVA light at a dose intensity of 5.6
mW/cm2 for 4 h resulted in a significant decrease in CAT and SOD activities and a
significant increase in TBARS. No cytotoxicity, as indicated by lactate
dehydrogenase (LDH) release, was observed. beta-Carotene (1 microM), lutein (1
microM) and astaxanthin (10 nM) protect against UVA light-induced oxidative
stress in vitro with astaxanthin exhibiting superior protective properties.
PMID- 9651821
TI - The relationship between the psychological and immunological state in patients
with atopic dermatitis.
AB - The relationship between the psychological and immunological state in patients
with atopic dermatitis was investigated. It was found that patients with atopic
dermatitis are significantly more depressive and scored higher for state anxiety
(P < 0.05) than the normal control group. They also tended to be more
psychosomatic symptom-prone and to score higher for trait anxiety. NK activity in
patients with atopic dermatitis was significantly lower than in normal controls
(P < 0.01), while serum IFN-gamma levels tended to be slightly higher and serum
IL-4 levels somewhat lower. No significant correlation was detected between any
pair of psychological test/immunological examination for either patients or
normal controls. However, in the examination of path analyses, psychological
variables affect serum levels of IFN-gamma and IL-4 more in the patients than the
normal controls. Only STAI(T) and (S) affect NK activity in atopic dermatitis
patients. By a discriminant analysis, NK cell activity and serum IFN-gamma
appeared statistically significant. We conclude that the psychological state is
to some extent related to the immunological state.
PMID- 9651822
TI - The pathogenesis of squamous cell cancer: lessons learned from studies of skin
carcinogenesis.
AB - This study used the induction of squamous cell carcinomas on mouse skin as an
experimental model to evaluate molecular and biochemical changes that contribute
to the neoplastic phenotype. The study was facilitated by the development of
keratinocyte cell culture assays that reproduce each stage of the carcinogenesis
process, by discoveries of stage-specific genetic and epigenetic changes and by
application of pharmacological and molecular tools that modify each step. An
early event in the transformation of keratinocytes involves mutation and
activation of the rasHa gene, producing a benign tumor. The phenotypic
consequences of ras mutations are mediated by activation of the epidermal growth
factor receptor (EGFR), upregulation of protein kinase C (PKC) alpha and AP-1
mediated transcriptional activity and inactivation of PKC delta through tyrosine
phosphorylation. These changes in benign tumors are manifested by
hyperproliferation (EGFR), aberrant expression of keratinocyte genes (PKC alpha
and AP-1) and delayed terminal differentiation (PKC delta). Accumulated
chromosomal abnormalities, multifocal phenotypic changes and alterations in gene
expression are associated with premalignant progression. Upregulation of the fos
gene and AP-1 transcriptional activity causes malignant conversion of benign
keratinocytes. In the absence of c-fos, benign tumor cells fail to upregulate
secreted angiogenic and proteolytic factors and this may prevent malignant
conversion. These pathways provide targets for preventive strategies to interrupt
the process of carcinogenesis prior to the evolution of the fully malignant
tumor.
PMID- 9651823
TI - Repeated subcutaneous injection of staphylococcal enterotoxin B-stimulated
lymphocytes retains epidermal thickness of psoriatic skin-graft onto severe
combined immunodeficient mice.
AB - Several approaches have recently been carried out to attempt to establish a mouse
transplantation model of psoriasis. To study the effects of superantigen-driven
peripheral blood mononuclear cells (PBMCs) on the persistence of psoriasiform
epidermis and cytokine gene expression of the grafted psoriatic skin,
staphylococcal enterotoxin B (SEB)-stimulated PBMCs (SEB-PBMCs) from psoriatic
patients were subcutaneously injected once or repeatedly under the grafted full
thickness involved psoriatic skin onto severe combined immunodeficient (SCID)
mice. After 5 weeks, the persistence of a psoriasiform epidermis was most
distinct in mice with repeated injection of SEB-PBMCs. E-selectin expression was
observed on endothelial cells in the upper dermis in mice with repeated injection
of both SEB-stimulated and unstimulated PBMCs, while mice with single injection
of unstimulated or SEB-PBMCs did not show positive staining. Both interleukin-1
beta (IL-1 beta) and interferon-gamma (IFN-gamma) mRNA were detected after 5
weeks, only in mice with repeated injection of SEB-PBMCs. It is concluded that
continuous supply of the activated PBMCs may help the persistence of psoriasiform
architecture more clearly, and that this transplantation mouse model may serve as
an in vivo model for the study of the pathogenesis and therapy of psoriasis.
PMID- 9651824
TI - Biochemical and immunohistochemical analyses of keratin expression in basal cell
carcinoma.
AB - Recently we demonstrated that the keratin 17 (K17) content exceeded the K16
content in most follicular tumors, in comparison with non-follicular epithelial
skin tumours by two-dimensional gel electrophoresis (2-DE), densitometry and
immunohistochemistry. At present the origin of basal cell carcinoma (BCC) is
unknown. So, based on the above results, we studied keratin expression in eight
cases of BCC, in order to analyze tumor differentiation by both biochemical and
immunohistochemical methods. Biochemically, using 2-DE and immunoblotting,
stratified epithelial keratins K5/K14 and large amounts of K17 were present in
all cases. Simple epithelial keratins K8 and K19 were expressed in all and half
of the cases, respectively. However, hyperproliferative associated keratins
(K6/K16) and keratinized keratins (K1/K10) were detected in only a few cases.
Immunohistochemical studies using frozen sections with chain-specific antikeratin
monoclonal antibodies against K1, K7, K8, K10, K14, K16, K17, K18 and K19 showed
that BCC tumor cells reacted positively with antibodies against K8, K14, K17 and
K19, but did not react, or were rarely positive with K1, K7, K10, K16 and K18
antibodies. Predominant expression of K17 and the frequent expression of K8 and
K19, with little K6/K16 and K1/K10 expression are the characteristic features of
BCC, suggesting that BCC is differentiated towards undifferentiated follicular
epithelia, most probably hair bulge cells.
PMID- 9651825
TI - Langerhans cells in prurigo nodularis investigated by HLA-DR and S-100
immunofluorescence double staining.
AB - The Langerhans cell is one of the antigen-presenting cells in the immune system.
To study the presence of cutaneous Langerhans cells in prurigo nodularis, age-
and sex-matched prurigo nodularis patients and healthy volunteer skin biopsies
were investigated by an HLA-DR and S-100 immunohistochemical double staining
method. The results showed that the HLA-DR- and S-100-immunoreactive (IR)
Langerhans cells were altered in prurigo nodularis epidermis and dermis. The
number of epidermal Langerhans cells in the prurigo nodularis patients was
decreased in five and increased in two cases. In the dermis, the HLA-DR- and S
100-IR cells were apparently more numerous than in the controls. In the involved
skin there were also more S-100-IR coarse nerve fibres in the dermis as compared
to controls. The results indicate that dermal Langerhans cells (HLA-DR and S-100
double-labeled) as well as other dermal HLA-DR- and S-100-IR dendritic cells, but
most likely not epidermal Langerhans cells, may be critically involved in the
development or persistence of prurigo nodularis.
PMID- 9651826
TI - Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after
hyperthermic isolated limb perfusion in patients with malignant melanoma: an
analysis of four cases.
AB - The lymphocytes isolated from perfused or non-perfused circulations before,
during, and after hyperthermic isolated limb perfusion (HILP) in the four
patients with malignant melanoma were analysed for the expression of CD54 (ICAM
1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the
mechanism(s) of the activation of such immunocompetent cells as natural killer
(NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte
populations expressing CD54 increased significantly 1 day after HILP in the four
patients examined. The lymphocyte populations expressing CD58 apparently
increased. It was also found that the NK-cell and T-lymphocyte activities
increased during or after HILP in the present four cases as observed previously
in the other melanoma patients. These results indicate that our HILP system may
augment the immunological activities through the mechanisms of the induction of
CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients
who receive HILP.
PMID- 9651827
TI - Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50
patients with cicatricial pemphigoid.
AB - In this study we investigated sera from 50 typical cicatricial pemphigoid (CP)
patients. By indirect immunofluorescence on 1 M NaCl-split human skin sections,
IgG of 17 sera and IgA of 22 sera reacted with the epidermal side of the split,
while IgG of two sera reacted with the dermal side. These latter two sera were
later confirmed to be anti-epiligrin CP. By immunoblotting of epidermal extracts,
IgG of 14 sera reacted with the 230 kD bullous pemphigoid (BP) antigen (BP230).
IgG of 15 sera and IgA of 11 sera reacted with the 180 kD BP antigen (BP180).
Interestingly, a bacterial fusion protein containing the BP180 NC16a domain was
recognized by IgG of 18 sera but not by IgA of any sera. Fusion proteins
containing the C-terminal region of BP180 were recognized by IgG of 20 sera, but
it was detected by IgA of only two sera. Our results suggest that, although CP
sera show very low titers of autoantibodies, a considerable number of sera
contain IgG antibodies to BP180 (either NC16a or C-terminal domain), confirming
previous studies. In addition, we showed that greater numbers of IgA antibodies
react with BP180, seemingly with different types of epitopes from those for IgG
antibodies. Because the specificity of IgG antibodies is not very different from
those in BP, IgA antibodies may play a specific role for the development of
characteristic clinical features in CP. Future studies should elucidate the
pathogenic role of the IgA antibodies in CP.
PMID- 9651828
TI - Increasing incidence of streptococcal impetigo in atopic dermatitis.
AB - Streptococcal impetigo associated with atopic dermatitis has dramatically
increased from 1989 to 1994 in outpatients visiting our hospital, totalling 174
cases. The most frequent causative agents were group A streptococci
(Streptococcus pyogenes, 70.7%) followed by group G (19.5%) and group B (9.8%).
Streptococcus was isolated singly in 28.2% of cases and in concomitant with
Staphylococcus aureus (S. aureus) in 71.8%. Major clinical features of
streptococcal impetigo, especially caused by group A streptococci, were non
bullous pustules with thick crusted ceiling. Impetigo caused by group G or B
streptococci generally formed smaller sized pustules of fewer numbers. Impetigo
was usually present, associated with severe eczematous lesions. Various degrees
of fever were noticed in 32.8% (group A, 39.8%; group G, 17.6%; group B, 11.8%)
during active stages. The lesions on the face often resembled Kaposi's
varicelliform eruption in any group. Systemic antimicrobial agents were
administered in 71.3% of cases and the remainder were treated with topical
antibiotics (oxytetracycline hydrochloride) or disinfectants (povidone-iodine).
Recurrence occurred within a month in 38.0% of cases treated with topical agents
only and in 17.7% treated with systemic antimicrobial agents. Antimicrobial
susceptibility tests and the results of treatment seem to indicate that cephems,
as well as penicillins, are the first choice of treatment for streptococcal
impetigo.
PMID- 9651829
TI - Hair follicle elongation in organ culture of skin from newborn and adult mice.
AB - By means of skin organ culture, some biological characteristics of hair follicle
elongation were examined. When skin sections from 6-day-old C3H mice were
cultured, spontaneous elongation of hair follicles was maintained. Without
insulin, hair follicle elongation was poorly maintained irrespective of the
presence of serum at 20%. Insulin could be replaced by IGF-I at 100 ng/ml. During
in vitro elongation of hair follicles, bromodeoxyuridine was incorporated into
germinal epithelial cells around dermal papillae. Skin sections from 4-week-old
C3H mice did not show hair follicle elongation in complete medium. However, when
0.5 mM minoxidil was added to the medium, concentration dependent thickening and
elongation of hair follicles was observed. In contrast, in vitro elongation of
newborn pelage hair follicles was not enhanced by minoxidil. These results
suggest that this system with the use of skin sections from 4-week-old C3H mice
would be a potential in vitro model of human androgenic alopecia in which the
anagen phase is suppressed but the suppression is partially released by
minoxidil.
PMID- 9651830
TI - Functional alteration of guanine nucleotide binding proteins (Gs and Gi) in
psoriatic epidermis.
AB - Psoriatic involved epidermis has been characterized by a defective beta
adrenergic adenylate cyclase response. It is also characterized by increased
cholera toxin- and forskolin-induced cyclic AMP accumulations. Due to the fact
that receptor signals are transduced to adenylate cyclase through guanine
nucleotides binding proteins (G-proteins), that affect cholera toxin- and
forskolin-induced cyclic AMP accumulations, possible alterations of G-proteins of
psoriatic involved and perilesional uninvolved epidermis by using toxin-catalyzed
ADP-ribosylation and immunoblot analyses was investigated. Cholera toxin
catalyzes ADP-ribosylation of stimulatory guanine nucleotides binding protein
(Gs) in either trimeric (inactive) or monomeric (active) form, while islet
activating protein (IAP) catalyzes ADP ribosylation of inhibitory guanine
nucleotide binding protein (Gi) in only trimeric (inactive) form. Results
indicate that although the psoriatic involved epidermis shows increased cholera
toxin- and IAP-catalyzed ADP-ribosylations, the amounts of immunoreactive Gs
alpha or Gi alpha are not significantly altered. The increase in IAP-catalyzed
ADP-ribosylation indicates increased inactive Gi, explaining the increased
forskolin-induced cyclic AMP accumulation. The increase in cholera toxin
catalyzed ADP-ribosylation of Gs explains the increased cholera toxin-induced
cyclic AMP accumulation in the psoriatic involved epidermis.
PMID- 9651831
TI - Effects of zinc oxide on the attachment of Staphylococcus aureus strains.
AB - We examined the attachment of Staphylococcus aureus to plastic tissue-culture
coverslips after incubation for 24 h. The attachment to coverslips was weaker in
rabbit plasma with 5% zinc oxide (ZnO) than in the control rabbit plasma without
ZnO (P < 0.01). Plasma coagulation by S. aureus strains was not detected in
plasma with 5% ZnO after incubation for 24 h. The membranous structure (an
immature biofilm) was formed on the coverslips by S. aureus cells in plasma after
incubation for 24 h. The colony counts of S. aureus cells on the membranous
structures were lower in plasma with 5% ZnO, plasma with 0.2% hinokitiol, plasma
with 5% ZnO + 0.2% hinokitiol, plasma with cefdinir at 4 minimum inhibitory
concentration (MIC) and plasma with levofloxacin at 4 MIC, than in the control
plasma after incubation for 24 h (P < 0.01). The colonies on the membranous
structures completely disappeared in the case of plasma with 5% ZnO and 0.2%
hinokitiol. The colony counts on membranous structures were lower in plasma with
cefdinir at 4 MIC or levofloxacin at 4 MIC containing 5% ZnO than in plasma with
cefdinir at 4 MIC or levofloxacin at 4 MIC only, (P < 0.05). The MICs of
hinokitiol against S. aureus strains peaked at an MIC distribution of 16-32
micrograms/ml. The peak shifted to below 1 microgram/ml by adding 5% ZnO in agar
plate method. The results suggest that the attachment of S. aureus cells to the
coverslips is suppressed in the presence of 5% ZnO and that antistaphylococcal
activities of cefdinir, levofloxacin and hinokitiol increase in the presence of
5% ZnO.
PMID- 9651833
TI - Current aspects of heart valve surgery.
PMID- 9651834
TI - Aortic root replacement: surgical implications.
PMID- 9651832
TI - Granulocytes enhance adhesion of peripheral blood mononuclear cells to dermal
endothelial cells.
AB - Interactions of all major peripheral blood leukocytes were studied during
adhesion to human dermal microvascular endothelial cells (HDMEC). Simultaneous
quantification of distinct leukocytic cell populations was carried in a recently
established adhesion assay followed by FACS analysis. Adhesion of stimulated
peripheral blood mononuclear cells (PBMC) was enhanced in the presence of
granulocytes compared to adhesion of PBMC alone. This effect required direct cell
cell contact as granulocyte supernatant in the absence of granulocytes failed to
yield the same extent of PBMC adhesion. Quantification of the common leukocyte
beta2-integrin subunit (CD18) and the common leukocyte beta1-integrin subunit
(CD29) as well as blocking with anti-CD18 antibodies revealed no differences
between PBMC adhering alone or in company of granulocytes to HDMEC. Blocking E
selectin, however affected 'mixed' (i.e., PBMC in the presence of granulocytes)
adhesion more profoundly than 'single' adhesion of PBMC. HDMEC subjected to
'mixed' leukocyte cell adhesion expressed E-selectin at 24 h after cytokine
stimulation, while HDMEC without contact to leukocytes did no longer express E
selectin at this time. In conclusion, functionally diverse peripheral blood
leukocytes can interact in order to enhance cell adhesion without up-regulation
of leukocytic integrin expression via an E-selectin dependent mechanism.
PMID- 9651835
TI - Aortic valve replacement with stentless porcine aortic valves: a ten-year
experience.
AB - BACKGROUND AND AIMS OF THE STUDY: It has been shown that although stentless
porcine aortic valves have better hemodynamic features than stented porcine
valves, their long-term durability remains unknown. This study was undertaken to
examine the long-term clinical outcome of aortic valve replacement (AVR) with
stentless porcine aortic valves. METHODS: Between 1987 and 1989, custom-made
stentless valves were implanted in 29 patients (mean age 58 years), and between
1991 and 1997, the Toronto SPV was implanted in 213 patients (mean age 63 years).
In addition to AVR, one-third of the patients had coronary artery bypass. All
patients were followed up at annual intervals and underwent Doppler
echocardiography. RESULTS: There were two operative and 11 late deaths (four
cardiac, seven non-cardiac). The actuarial survival rate was 89 +/- 4% at nine
years. There were two strokes and seven transient ischemic attacks; freedom from
thromboembolic complications was 92 +/- 4% at nine years. Two patients developed
infective endocarditis, one early and one late; freedom from prosthetic valve
endocarditis was 98 +/- 1% at nine years. Freedom from primary tissue failure was
85 +/- 8% at nine years. Seven patients required repeat AVR, because of
endocarditis (two) and aortic insufficiency (five); freedom from repeat AVR was
82 +/- 8% at nine years. Periodic hemodynamic assessment by echocardiography
indicated that the mean systolic gradients across the valve decreased during the
first year of implantation, the valve effective orifice increased, and valve
competence remained stable. CONCLUSIONS: Stentless porcine aortic valves have
provided excellent clinical results. These valves may suffer degenerative changes
and fail at the same rate as stented porcine aortic valves but, because of their
superior hemodynamic performance, they may enhance patients' survival by allowing
complete regression of left ventricular hypertrophy and restoration of normal
ventricular function.
PMID- 9651836
TI - Mitral valve repair: an odyssey to save the valves!
AB - The history of mitral valve repair surgery is an interesting odyssey that has
nearly spanned the century. However, since the mid 1970s, both European and North
American surgeons have developed and expanded these techniques to where repair of
myxomatous valves is now expected by most cardiologists and patients.
Preoperative functional assessment is most important to determine the specific
needs for repair. Today, transesophageal echocardiography is the standard by
which cardiologists and surgeons rely for these data. Herein, both methods of
assessment and techniques for repair are detailed. The multidisciplinary approach
is emphasized. Risks of surgery are detailed as well as long-term outcomes
compared with replacement of the mitral valve. Lastly, surgical results from the
235 patients repair series at the East Carolina University School of Medicine are
detailed and discussed. This series showed a 1.8% mortality rate for myxomatous
valve patients, with a very low reoperative rate. This compared with a higher
mortality rate of 5.6% for the overall group, which emphasizes the increased risk
associated with an ischemic etiology. The author provides not only an overview
but also tips to surgeons beginning to repair valves.
PMID- 9651837
TI - Evaluation of in vivo models for studying calcification behavior of commercially
available bovine pericardium.
AB - BACKGROUND AND AIM OF THE STUDY: A common frame of reference is essential when
attempting to determine if new treatments intended to reduce calcification of
bioprostheses are superior to existing processes and products. The aim of this
study was to examine calcification behavior for a commercially available
pericardial bioprosthesis in subcutaneous and sheep valve models, and to evaluate
the importance of appropriate control treatments in comparative studies with
proposed new treatments. METHODS: Samples of bovine pericardium were placed
subcutaneously under the dorsal skin of weanling rats and juvenile rabbits for 30
, 60- and 90-day intervals. Samples were either commercially available
pericardial tissue or tissue processed with phosphate-buffered glutaraldehyde
alone. Commercially available pericardial valves were also implanted in the
mitral position in juvenile sheep, with elective sacrifice at 20 weeks. Retrieved
samples underwent X-ray, histologic and elemental analysis. RESULTS: Commercial
samples retrieved from the subcutaneous and sheep models showed similar, minimal
calcification behavior on X-ray and histologic slides, whereas pericardium
exposed to glutaraldehyde alone demonstrated rapid calcification. CONCLUSIONS:
The 90-day subcutaneous rabbit model produced patterns of calcification similar
to those in valves explanted from juvenile sheep after 20 weeks. A statistically
significant decrease (p < 10(-8)) in calcification was demonstrated for clinical
pericardium when compared with pericardium exposed to glutaraldehyde alone in the
subcutaneous model. This suggests that subcutaneous models may be a cost
effective, time-efficient means of evaluating and comparing various tissue
treatment methods. The rabbit methodology may provide a more accurate prediction
of clinical performance, offering a greater degree of sensitivity. These studies
also indicate that the commercially available process shows minimal calcification
in the commonly used 30-day weanling rat subcutaneous model, contradicting other
reported studies that may not accurately represent commercially available
processes.
PMID- 9651838
TI - An in vitro bovine pericardial hemocompatibility testing system.
AB - BACKGROUND AND AIMS OF THE STUDY: Bovine pericardium has been used as a
biomaterial for heart valves since the late 1960s. Cross-linking agents have been
applied routinely to reduce host-tissue response, including antigenicity, and to
improve tissue leaflet durability. Evaluation of improvements in bovine
pericardial valve leaflet calcification and flexibility require that in vitro
systems be developed to correlate data with results from in vivo studies. This
study describes an in vitro test system used to evaluate the effects of two
surface-modifying treatments on pericardial tissue hemocompatibility. METHODS:
Non-fixed and glutaraldehyde fixation-processed (GA) bovine pericardial tissues
were exposed to anticoagulated whole blood for 60 min. Blood was then removed,
and platelet-poor plasma prepared and frozen at -70 degrees C until analyzed for
kallikrein activation and release of platelet factor 4 (PF4). Blood-exposed
tissue samples were analyzed for fibrin (ogen) binding with an anti-fibrinogen
antibody and for tissue cellular responsiveness (blood cell adherence and
aggregation) by scanning electron microscopy. RESULTS: Conditions were determined
for minimum extent of pumping action by the minicam system required to allow for
solution movement while not tearing or wearing the tissue. A blood-tissue
exposure time of 60 min provided sufficient first-pass exposure to evaluate the
acute blood-tissue response. The relative degree of both kallikrein activation
and PF4 release was greater in the non-fixed tissue but a greater number of
fibrin(ogen) molecules per cm2 was found on GA-treated tissue. Scanning electron
microscopy showed a differential cell response of non-fixed tissue compared with
GA-treated tissue. CONCLUSION: This non-static test system demonstrated great
promise for use in routine in vitro hemocompatibility testing of blood-contacting
biological biomaterials.
PMID- 9651839
TI - Comparative assessment of hepatic Glisson's capsule and bovine pericardium in
heart valve bioprostheses.
AB - BACKGROUND AND AIM OF THE STUDY: The optimal material for heart valve
bioprostheses remains disputable. This investigation was initiated to compare the
properties of hepatic Glisson's capsule, clinical experience of which in
cardiovascular surgery is minimal, with those of bovine pericardium. METHODS:
Hepatic Glisson's capsule was harvested from bull calves and used to create
composite pulmonary arterial monocusp grafts and bioprostheses. Comparison of the
strength and elastic properties of Glisson's capsule and bovine pericardium, as
well as the hydrodynamic characteristics of valves made from these materials, was
performed. Late results of operations using these materials were estimated
echocardiographically. RESULTS: Although Glisson's capsule tissue is thinner than
the bovine pericardium, its elasticity modulus is greater. However, the
hydrodynamic characteristics of heart valves made from either tissue are similar.
Moreover, valves made from Glisson's capsule have a lower systolic pressure
gradient on the prosthesis and a higher effective orifice area. Composite
pulmonary arterial xenopericardial grafts with a monocusp of Glisson's capsule
were used in 30 patients during tetralogy of Fallot repair. Glisson's capsule was
also used for tricuspid valve reconstruction and as a bioprosthesis in six
patients with Ebstein's anomaly. At 1-2 years after surgery, the Glisson's
capsule tissue remained thin and flexible, with no calcification. CONCLUSIONS:
Although the hydrodynamic properties of hepatic Glisson's capsule and the bovine
pericardium are similar, the capsule tissue is thinner and has a greater
elasticity modulos. Thus, Glisson's capsule may be used for bioprosthesis
construction both independently and in combination with bovine pericardium.
PMID- 9651840
TI - Long-term results with the Sorin Pericarbon valve in the aortic position: a
multicenter study.
AB - BACKGROUND AND AIM OF THE STUDY: A multicenter study was designed to evaluate the
Pericarbon pericardial bioprosthesis for up 10 years after implantation in the
aortic position. METHODS: Between January 1986 and November 1996, 321 patients
(mean age 75.8 +/- 7.3 years) received 325 Pericarbon pericardial valves in the
aortic position. Four patients underwent redo surgery and each received a second
Pericarbon prosthesis. Associated cardiac procedures in 80 patients were mainly
coronary bypass (n = 66). Follow up extended up to 10 years (cumulative follow up
of 931.0 patient-years; mean follow up 3.1 +/- 2.2 years). RESULTS: There were 19
late deaths, with seven valve-related. Twelve patients suffered an embolic
complication (transient cerebral attack in four, peripheral in six and induction
of a myocardial infarction in two). Of these complications, five occurred within
30 days of surgery and seven beyond the first year. Ten patients were reoperated
on, six for primary tissue failure, two for prosthetic endocarditis and two for
paraprosthetic leak. Primary failure was due in all cases to leaflet
mineralization. No primary tear of the leaflet was reported. Actuarial freedom
after 10 years from primary tissue failure was 83.9 +/- 7.4% and from major
embolic events 97.6 +/- 1.0%. Freedom from valve-related mortality at 10 years
was 92.1 +/- 4.9%. CONCLUSIONS: These results indicate that, over a period of up
to 10 years, the Pericarbon pericardial bioprosthesis compares favorably with
other replacement valves.
PMID- 9651841
TI - Detoxified glutaraldehyde cross-linked pericardium: tissue preservation and
mineralization mitigation in a subcutaneous rat model.
AB - BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde is considered a promoter of
calcification by the action of toxic aldehyde group residuals from cross-linking.
Post-fixation treatment with homocysteic acid (HA), besides bonding aldehyde
groups and neutralizing toxicity, should enhance biocompatibility due to the
strongly electronegative sulfonic group. The aim of this investigation was to
evaluate HA efficacy on tissue preservation and dystrophic calcification
mitigation in glutaraldehyde cross-linked bovine pericardium (BP) using a
subcutaneous rat model. METHODS: Four samples of BP, two with glutaraldehyde-HA
and two with glutaraldehyde treatment, were implanted in each of 24 male Sprague
Dawley rats. Three rats were killed at 14 days, eight at 28 days, eight at 56
days and five at 84 days. Unimplanted glutaraldehyde-HA- and glutaraldehyde
treated samples served as controls. All samples were studied by gross
examination, mammography, light transmission and scanning electron microscopy,
and atomic absorption spectroscopy. The nature of mineralization was investigated
by coupling techniques of scanning electron microscopy, electron microprobe
analysis and X-ray powder diffraction. RESULTS: No histological and
ultrastructural differences were found between glutaraldehyde-HA- and
glutaraldehyde-treated BP, whether implanted or unimplanted. In both groups,
calcification progressed with time, but significantly less after glutaraldehyde
HA treatment than after glutaraldehyde alone and at all time intervals (14.63 +/-
21.34 versus 43.17 +/- 15.99 at 28 days, p = 0.003; 56.42 +/- 40.20 versus 90.59
+/- 32.90 at 56 days, p = 0.008; 91.68 +/- 67.68 versus 156.23 +/- 17.85 at 84
days, p = 0.01). Differences were evident by mammography and histology (von Kossa
stain). Electron microprobe analysis in both groups showed the composition of
calcified nuclei to be calcium phosphate, stoichiometrically close to apatite
(Ca5(PO4)3(OH)). The occurrence of crystallized apatite was supported by X-ray
powder diffraction findings, the amount of crystallized apatite being higher in
glutaraldehyde-treated samples. CONCLUSIONS: Post-fixation treatment with HA
preserves BP structural properties and significantly mitigates mineralization of
long-term subcutaneous implants.
PMID- 9651842
TI - Twelve-year experience with Carpentier-Edwards PERIMOUNT pericardial valve in the
mitral position: a multicenter study.
AB - BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess the durability of
the Carpentier-Edwards PERIMOUNT pericardial bioprosthesis in the mitral
position. METHODS: This seven-center retrospective clinical study involved the
follow up of 333 patients who underwent isolated mitral valve replacement and 102
patients who underwent double (mitral and aortic) valve replacement with the
PERIMOUNT pericardial valve between 1984 and 1989. Mean patient age at implant
was 60.7 +/- 11.6 years; 41.1% were males. The most common etiology was rheumatic
heart disease (53.9%) and the most common mechanism mitral insufficiency. All
patients but six were followed for an average of 7.2 +/- 3.6 years after surgery;
total follow up was 3071.7 patient-years (pt-yr). RESULTS: The total operative
mortality rate was 7.6%; this included a valve-related mortality rate of 0.2%.
The late mortality rate was 5.2% per pt-yr, of which 1.4% per pt-yr was
considered valve-related. At 11 years, the overall actuarial survival rate was
53.3 +/- 2.8%, and actuarial freedom from valve-related death 83.9 +/- 2.6%. At
follow up, 80% of patients were in NYHA class I or II, and 74% showed
improvement. Twenty-eight incidences of deterioration requiring explant were
observed. At 11 years the actuarial freedom from explant due to structural
failure was 84.9 +/- 3.1%. Rates of structural failure decreased with age: the
actuarial freedom from explant due to structural failure was 78.1 +/- 4.8% for
patients aged < or = 60 years, 89.4 +/- 4.4% for those aged 61-70 years, and 100%
for those aged over 71 years. CONCLUSION: The Carpentier-Edwards PERIMOUNT
pericardial bioprosthesis is a reliable choice when a tissue valve is required,
especially in patients over 60 years of age.
PMID- 9651843
TI - Enlargement of the aortic annulus with glutaraldehyde-fixed bovine pericardium
during aortic valve replacement.
AB - BACKGROUND AND AIMS OF THE STUDY: Aortic valve replacement in patients with a
small aortic annulus may represent a surgical challenge. We have evaluated a
simplified technique to enlarge the aortic annulus which consists of extending
the aortotomy incision to divide the commissure between the left and non-coronary
cusps into the interleaflet triangle without opening the left atrium. METHODS:
This technique was used in 16 patients (15 women, one man; mean age 66 +/- 9
years) who underwent aortic valve replacement between August 1994 and February
1996. Aortic stenosis was the predominant valvular lesion. A mechanical
prosthesis was implanted in 13 patients (81%) (21 mm in six, 23 mm in seven)
while three received a bioprosthesis (21 mm in one, 23 mm in two). In all
patients it was possible to insert a prosthesis at least one size larger than the
original aortic annulus diameter. RESULTS: There were no operative deaths and no
late deaths. Mean follow up was 20 +/- 6 months (range: 12 to 30 months).
Echocardiographic controls at 12 months postoperatively showed no evidence of
periprosthetic leaks or mitral regurgitation. Comparison with preoperative data
showed no significant variations of mean aortic diameter at the sinus level (30.7
+/- 2.2 mm versus 31.3 +/- 2.6 mm) or at the sinotubular junction (33.6 +/- 2.7
mm versus 34.3 +/- 2.9 mm) (p = NS). Significant reduction of left ventricular
mass was observed (314 +/- 57 g versus 260 +/- 45 g; p < 0.001). CONCLUSIONS:
This technique is simple, reproducible and effective in allowing adequate
enlargement of the aortic annulus and provides excellent clinical and hemodynamic
results. Glutaraldehyde-fixed bovine pericardium used as a patch material showed
no tendency to aneurysmal dilatation with progression of time at a maximum follow
up of 30 months.
PMID- 9651845
TI - Better understanding of the pathogenesis of prosthetic valve endocarditis--recent
perspectives for prevention strategies.
PMID- 9651844
TI - Aortic reconstruction with crimped bovine pericardial conduits.
AB - BACKGROUND AND AIM OF THE STUDY: A bovine pericardial conduit processed in
glutaraldehyde was designed, incorporating the principle of crimping used for
synthetic vascular prostheses. The crimping process did not affect the integrity
of collagen fibers and tissue structure. This conduit, designed for aortic
reconstruction, is available in different sizes, with or without a biological
valve. METHODS: Between October 1989 and May 1997, 40 patients with aortic
dissection, aortic aneurysm, aortic coarctation or aortoiliac occlusive disease
underwent aortic reconstruction using this vascular substitute. Procedures
included total reconstruction of the ascending aorta and aortic valve with
reimplantation of coronary arteries (nine patients), single ascending thoracic
aorta (six), descending thoracic aorta (two), aortic arch (one) and
thoracoabdominal aorta (one); the abdominal aorta was reconstructed in 21 cases,
including those undergoing aortoiliac or aortofemoral bypass. RESULTS: The
hospital mortality rate was 20% (eight patients); causes of deaths were low
cardiac output, recurrence of aortic dissection, multiple organ failure and
bleeding. Mean follow up was 3.6 years; total follow up was 114 patient-years.
Late conduit-related complications occurred in four patients, including a limb
obstruction in one patient subjected to aortofemoral bypass and infection of
three resulting in pseudoaneurysm (incidence of 3.5 +/- 1.8% per patient-year).
All underwent reoperation. There were four late deaths due to sudden death,
coronary artery disease, pneumonia and metabolic complications of diabetes and
renal failure (incidence of 3.5 +/- 1.8% per patient year). The eight-year
actuarial survival rate was 63.7 +/- 11.6%, including hospital mortality, and the
eight-year actuarial freedom from conduit failure due to primary tissue
structural degeneration was 100%. CONCLUSIONS: The crimping design provides a
circular tube which makes construction of the anastomosis easier, retains its
shape with bending, and avoids kinking. The material is very soft, easy to handle
and suture, coapts nicely to suture lines resulting in a hemostatic anastomosis.
The eight-year follow up demonstrated a satisfactory performance without report
of fibrosis, calcification or aneurysmal dilation.
PMID- 9651846
TI - Strategies for prophylaxis against prosthetic valve endocarditis: a review
article.
AB - Prosthetic valve endocarditis (PVE) is an important cause of the morbidity and
mortality associated with heart valve replacement surgery. Once established, it
carries a mortality rate that may be as high as 70%. The only treatment for
established PVE is rigorous intravenous antimicrobial therapy, although this has
extremely limited success. The majority of cases require surgical removal and
replacement of the infected prosthesis. At present, the only means of preventing
PVE are scrupulous asepsis and prophylactic perioperative antibiotic therapy. If
another strategy could be developed that is effective and safe, the incidence of
this disastrous complication of valve replacement would be reduced. Such
strategies have been extensively investigated from a variety of different
perspectives for several years. The understanding of biofilms appears to be
pivotal to the development of a successful approach. The historic background to
the prevention of PVE, and the current state of research into this area are
discussed.
PMID- 9651847
TI - Histopathologic comparison of a pulmonary autograft and pulmonary homograft in a
patient 17 months after a Ross procedure: an autopsy study.
AB - BACKGROUND AND AIM OF THE STUDY: The Ross operation has become very popular
during the last decade. However little is known about the cellular behaviour of a
normally functioning pulmonary autograft. METHODS: This case report deals with a
14-year-old female who died from a non-valve-related cause 17 months after a Ross
Konno operation using a cryop-reserved viable pulmonary homograft for the right
outflow tract. Comparison is made between the homologous and autologous pulmonary
valves by macroscopic description, histology and immunohistochemistry. RESULTS:
The autograft kept its cellular population-except for the dendritic cells which
have disappeared, and developed a jet lesion on the ventricular aspect of one
cusp as a likely adaptation to a transvalvular gradient. The homograft was
extensively devitalized, its cusps being partially covered with a fibrous sheath
of recipient origin; few inflammatory cells, consisting of macrophages and rare T
lymphocytes were present. CONCLUSIONS: The most puzzling observation, which needs
confirmation, is the selective disappearance of the dendritic cells from the
viable autograft. It is disappointing that a viable cryopreserved homograft valve
has devitalized in the midterm. This phenomenon seems to result from a clinically
silent immune reactions.
PMID- 9651848
TI - Clinical experience with the Carpentier-Edwards supra-annular porcine
bioprosthesis implanted in the aortic position.
AB - BACKGROUND AND AIMS OF THE STUDY: Between 1st January 1988 and 30th June 1996, a
total of 165 patients (115 males, 50 females; mean age 66.8 years) underwent
isolated aortic valve replacement with Carpentier-Edwards supra-annular porcine
bioprostheses in our unit. Our clinical experience with this device is reported.
METHODS: In this retrospective study, mortality and complications observed in
these patients were analyzed. Complications appearing with a non-biased time
course were expressed by means of linearized rates. Actuarial analysis was
performed using the Kaplan-Meier method. RESULTS: Cumulative follow up was 551.2
patient-years, with a mean follow up of 3.5 years per patient. The hospital
mortality rate was 6.7%. Linearized rates (events per 100 patient-years) and
actuarial probabilities of freedom from the different complications at 8.5 years
follow up, respectively, were: late mortality, 4.5 and 58.6%; valve-related
mortality, 1.1 and 82.6%; thromboembolism, 1.3 and 92.7%; prosthetic
endocarditis, 0.5 and 97.4%; non-structural dysfunction, 0.5 and 94.7%;
structural deterioration, 0.5 and 91.6%; reoperation, 0.5 and 94.2%. Actuarial
freedom from any valve-related mortality or morbidity at 8.5 years was estimated
at 66.3%. CONCLUSIONS: The Carpentier-Edwards supra-annular bioprosthesis, when
implanted in the aortic position, presents a low rate of valve-related
complications at this length of follow up. However, the limited life expectancy
of our patients undergoing aortic valve replacement with bioprostheses (usually
elderly subjects) may overshadow the potential good performance of this device.
PMID- 9651849
TI - In vitro effects of anticalcification treatment on the calcium uptake of
bioprosthetic materials.
AB - BACKGROUND AND AIM OF THE STUDY: The frequent need for re-replacement of tissue
valves due to calcification remains their major disadvantage compared with
mechanical implants. A variety of anticalcification treatments has been proposed
but none has proved to prevent calcific degeneration. The study aim was to
evaluate, in vitro, the time course of calcium uptake of procine and bovine
biomaterials and the efficacy of anticalcification treatments. METHODS: Samples
of glutaraldehyde-tanned biomaterials with (Carpentier-Edwards, Medtronic Intact,
Hancock II, MZGTB) or without anticalcification treatment (Mitroflow) were
incubated with culture medium containing physiological calcium levels. Specimens
were then analyzed at two, four or eight weeks for their calcium content (mg/g
wet weight). RESULTS: All specimens calcified over time, though the time courses
for each were significantly different. Mitroflow and Intact valves accumulated
high calcium levels rapidly during the first two weeks, with small further
increases thereafter. Anticalcification treatment reduced calcium uptake of
Carpentier-Edwards material during the first two weeks of incubation, but the
material gradually attained comparable calcium levels at eight weeks. Hancock
valves and the self-customized MZGTB valve showed the lowest calcium levels over
the test period. CONCLUSIONS: This in vitro study documented major differences in
calcium uptake of different biomaterials. Some anticalcification treatments
render the material temporarily less susceptible to calcium binding but none can
prevent calcification. In vitro testing has proved to be a valuable instrument
for evaluating anticalcification treatments, but should be combined with
evaluation of bioprosthesis surface interaction with circulating blood.
PMID- 9651850
TI - Prevalence of microbubbles associated with mechanical prosthetic cardiac valves:
a prospective transesophageal echocardiography study.
AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to identify the prevalence of
microbubbles in different types of mechanical cardiac valve and, if feasible, to
associate microbubbles with various clinical conditions, including thrombotic
occlusion of the valves. METHODS: A total of 153 mechanical prosthetic valves
were studied (58 aortic, 95 mitral) in 140 patients, prospectively. All valves
were functioning normally. In addition, eight mitral prosthetic valves were
selected without microbubbles and with an obstructive valvular thrombosis that
had undergone successful thrombolysis (group 1); a further eight patients with
unsuccessful thrombolysis (group 2) were studied by transesophageal
echocardiography before and after thrombolytic therapy. RESULTS: Microbubbles
were detected in 75% (114/153) of prosthetic valves, 99% (88/89) of bileaflet
valves, and 45% (29/64) of monoleaflet valves (p < 0.0001). Only 14% (4/28) of
Sorin monoleaflet valves were associated with microbubbles, which is
distinctively less than other valves (p < 0.001 for each); 71% and 77% of aortic
and mitral prosthetic valves, respectively, were associated with microbubbles (p
= NS). Prosthetic valves with an obstructive thrombosis and no microbubbles in
group 1 showed new appearance of microbubbles in 88% (7/8) of cases after
successful thrombolysis. Absence of microbubbles in group 2 persisted in all
eight patients at the second examination. CONCLUSIONS: Microbubbles were detected
in a greater proportion of patients than reported previously and were found to be
associated more with bileaflet prosthetic heart valves than with monoleaflet
valves. Sorin monoleaflet valves were associated with microbubbles dramatically
less than all other valves. The new appearance of microbubbles after thrombolytic
therapy of mechanical prosthetic heart valves with an obstructive thrombosis may
indicate successful thrombolysis.
PMID- 9651851
TI - The hemodynamic effects of mechanical prosthetic valve type and orientation on
fluid mechanical energy loss and pressure drop in in vitro models of ventricular
hypertrophy.
AB - BACKGROUND AND AIMS OF THE STUDY: When choosing a prosthetic replacement for a
natural heart valve, one objective should be to minimize the workload placed on
the heart. This workload can be raised by fluid mechanical energy losses imposed
by the valve. For a patient with left ventricular hypertrophy, certain aortic
valve types and orientations could be hemodynamically superior to others.
METHODS: This study used a control volume analysis to investigate the effects of
prosthetic mechanical aortic valve type and orientation on fluid mechanical
energy losses in four in vitro models of the left ventricular outflow/aortic
inflow tract in various degrees of hypertrophy. Flow visualization studies were
performed to qualitatively validate this analysis. The two most commonly used
mechanical valve designs were studied: the St. Jude Medical (SJM) bileaflet valve
and the Medtronic Hall (MH) tilting disk valve. Experiments were performed in
pulsatile flow at a constant heart rate of 60 beats per min for five valve
type/orientation combinations. The stroke volume was varied between 40 and 120 ml
in five increments for each model and valve/orientation studied. RESULTS: Valve
type and orientation was found to have a significant effect on energy losses in
these models (p < 0.05). Valve/orientation combinations with leaflets or disks
approximately parallel to the proximal flow direction created lower energy losses
than others. The MH valve in the 180 degrees orientation caused significantly
less energy losses and pressure drops (orifice and recovered) than any of the SJM
valve/orientations studied (p < 0.05). The SJM and MH valves in the 0 degree
orientation were responsible for significantly more energy loss than other
valve/orientations studied (p < 0.05). An aortic inflow tract model with severe
(45 degrees) curvature created significantly more energy loss (p < 0.05) than
those with less curvature (15 and 30 degrees). However, the insertion of an
obstruction simulating a hypertrophic tissue outgrowth caused much more energy
loss than increasing the severity of outflow tract curvature from 15 to 45
degrees. Both orifice pressure drop and recovered pressure drop had excellent
linear correlations with energy losses found in these models. CONCLUSIONS: These
results imply that: (i) prosthetic valve type and orientation should be
considered when replacing the aortic valve of a hypertropic patient; (ii) removal
of obstructions within the aortic inflow tract will decrease ventricular
workload; and (iii) the Doppler-estimated pressure gradients commonly use by
cardiologists to assess the performance of a prosthetic valve, correlate very
well with left ventricular energy loss and work load.
PMID- 9651852
TI - Hypertrophic cardiomyopathy in pregnancy. The use of two-dimensional and Doppler
echocardiography during labor and delivery: a case report.
AB - Hypertrophic cardiomyopathy (HCM) in pregnancy can result in a high incidence of
maternal complications. Although echocardiography is frequently performed in
pregnant women with HCM in order to confirm their hemodynamic classification,
this modality has not been applied during labor and delivery in these patients.
This case report documents the application of two-dimensional and Doppler
echocardiography during labor and delivery in a 35-year-old woman with HCM.
PMID- 9651853
TI - Trying to control MRSA causes more problems than it solves.
AB - Despite occasional reports of local success, the steadily increasing prevalence
of strains of Staphylococcus aureus resistant to methicillin (MRSA) shows that
attempts to limit their spread do not work. In this commentary we suggest that
efforts to control the spread of methicillin-resistance are counterproductive,
and that energies should instead be directed towards the control of outbreaks of
disease and preventing the emergence of antibiotic resistance.
PMID- 9651854
TI - The epidemiology and prevention of invasive aspergillosis.
AB - Over the past two decades, the incidence of invasive aspergillosis (IA) has risen
inexorably. This is almost certainly the consequence of the more widespread use
of aggressive cancer chemotherapy regimens, the expansion of organ transplant
programmes and the advent of the acquired immunodeficiency syndrome (AIDS)
epidemic. Despite the development of new approaches to therapy, IA still remains
a life-threatening infection in immunocompromised patients and is the most
important cause of fungal death in cancer patients. It is clear that the
prevention of severe fungal infection by the use of effective infection control
measure should be the priority of the teams involved in managing at-risk
patients. The evidence from clinical and molecular epidemiological studies is
reviewed and current thinking on sources and routes of transmission of the
organism are discussed. Our increasing understanding of these has led to the
development of a variety of environmental and general strategies for the
prevention of IA. It is anticipated that these, coupled with the use of
prophylactic antifungal agents active against Aspergillus spp., will have a
significant impact upon the morbidity and mortality associated with this
infection.
PMID- 9651855
TI - An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital.
AB - We describe the epidemiology and control of a hospital outbreak of multi-drug
resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative
patient with drug-sensitive tuberculosis developed MDR-TB during a period of
unsupervised therapy. She was admitted to an isolation room in a ward with HIV
positive patients, but the room, unbeknown to hospital staff, was at positive
pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB.
The diagnosis in the second patient was delayed, partly because acid-fast bacilli
in his sputum were assumed to be Mycobacterium avium-intracellulare. All the
available Mycobacterium tuberculosis isolates were indistinguishable by molecular
typing. Nearly 1400 staff and patient contacts were offered screening, but the
screening programme detected only one of the cases. Despite therapy, the index
patient and two of the contacts died. HIV-positive patients are more likely than
others to develop tuberculosis after exposure, and the disease may progress more
rapidly. In these patients the possibility that acid-fast bacilli may represent
M. tuberculosis must always be considered. Patients with tuberculosis (suspected
or proven) should not be nursed in the same wards as immunosuppressed patients,
and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms.
Hospital side-rooms may be positive-pressure as a fire safety measure; infection
control teams must be aware of the airflows in all isolation rooms, and must be
consulted during the design of hospital buildings. Good communication between
infection control teams and clinicians is important, and all medical and nursing
staff must be aware of the principles of management of patients with proven or
suspected tuberculosis and MDR-TB.
PMID- 9651856
TI - Comparison of wound scoring methods for use in audit.
AB - Accurate information on the prevalence of surgical wound infection is difficult
to obtain; outpatient follow-up is often inadequate. For two months in 1993 and
again in 1995, surgical wounds throughout one hospital were examined by the same
observer with the intention of comparing different methods for assessing wound
infection. Two standard definitions [Centers for Disease Control (CDC), USA and
National Prevalence Survey (NPS), UK] were compared with ASEPSIS and the
Southampton method. In 1993, 325 wounds in 230 patients were examined with follow
up of 203 (88%) patients. In 1995, 559 wounds were surveyed in 375 patients with
follow-up in 364 (97%). Patient groups in the two years were similar. ASEPSIS
identified 92 (13%) wounds as having scored over 20 points indicating infection,
and another 16.5% having disturbance of healing. There was no significant
difference between the two surveys. The two scoring methods were more sensitive
than the standard definitions but CDC and NPS did not differ significantly from
each other. Between 44 and 47% of clean wounds identified as infected by standard
definitions were classed as disturbance of healing by ASEPSIS. All methods were
labour-intensive and to implement any one of them on a regular basis would
require a full-time investigator. The first surveillance program with feedback of
results to the surgeons did not significantly affect the rates two years later.
PMID- 9651857
TI - Ventilation grilles as a potential source of methicillin-resistant Staphylococcus
aureus causing an outbreak in an orthopaedic ward at a district general hospital.
AB - The spread of methicillin-resistant Staphylococcus aureus (MRSA) in a hospital is
thought to be mainly by direct contact. Environmental sources such as exhaust
ducting systems have been increasingly recognized as a source for MRSA outbreaks
in intensive therapy units. We describe an outbreak of MRSA related to
ventilation grilles in an orthopaedic ward. Six patients and one nurse were
involved in an outbreak with EMRSA-15 during March 1996. The index case was
transferred from a large university hospital in Leeds. One of the patients had
shared the same bay with the index case. The rest of the patients were in another
bay of the same ward and had no direct contact with the index patient. An
environmental source was suspected and the ventilation grilles in boys 1 and 2
were found to be harbouring EMRSA-15. The ventilation system at that time was
working on an intermittent cycle from 4 p.m.-8 a.m. Daily shut-down of the system
temporarily created a negative pressure, sucking air in from the ward environment
into the ventilation system and probably contaminating the outlet grilles. It is
likely that contaminated air was blown back into the ward when the ventilation
system was started. The system was thoroughly cleaned, appropriate infection
control measures were instituted and the ventilation system was put back on a
continuous running cycle and the outbreak terminated. Six months after the
outbreak no isolates of EMRSA-15 had been made on the ward.
PMID- 9651858
TI - An outbreak of an unusual strain of Serratia marcescens in two Dublin hospitals.
AB - We describe a serious outbreak of infection caused by a strain of Serratia
marcescens in two Dublin hospitals which occurred over an 11 week period and
affected a total of 15 patients. A contaminated bed-pan macerator in the
Intensive Care Unit of one hospital was identified as the possible source of
infection and spread of the organism probably occurred via hand transmission by
hospital personnel and via patient transfer to a second hospital. All isolates of
S. marcescens involved in the outbreak had the same antimicrobial susceptibility
pattern, with reduced susceptibility to gentamicin, cefotaxime and ciprofloxacin.
Epidemiological typing revealed that the strains of S. marcescens isolated in the
outbreak were of an uncommon serotype, O21:K14, and using pulsed-field gel
electrophoresis, XbaI DNA macrorestriction profiles clustered at 90% similarity.
The DNA patterns of the outbreak strain were also highly similar to S. marcescens
isolates of the same serotype recovered from a separate Dublin hospital during
the same time period as the outbreak described here. In addition, the isolates
clustered at 82% similarity with strains of the same serotype from a
retrospective collection of S. marcescens isolates from various hospitals in the
Dublin area, indicating that these may be genetic variants of the same strain.
Although the outbreak was brought under control following implementation of
infection control measures, a significant number of similar O:21 isolates of S.
marcescens have since been identified in four Dublin hospitals. These results
suggest the unique spread of a single strain of S. marcescens in Dublin
hospitals.
PMID- 9651859
TI - Incidence of nosocomial pneumonia in a medical intensive care unit and general
medical ward patients in a public hospital in Bombay, India.
AB - We prospectively studied the incidence of hospital-acquired pneumonia in 1886
consecutive admissions to an 1800 bed hospital in Bombay; 991 of them to general
medical wards and 895 to a 17-bed medical intensive care unit (ICU). The average
bed occupancy in the general wards was 56 patients in a ward with 40 beds.
Staffing in the general ward was two nurses for 56 patients, and in the ICU three
nurses for 17 beds. One hundred and sixty-eight patients developed nosocomial
pneumonia: 18 (1.8%) in general wards and 150 (16.7%) in the ICU. Common isolates
included Pseudomonas spp (44%) and Klebsiella spp (34%). The most frequently used
antibiotics were cefotaxime (34%), amikacin (25%), gentamicin (23%) and ofloxacin
(13%). Crude mortality in general ward patients was 88.9 vs 14.6% in patients
without pneumonia. The corresponding figures for ICU patients were 67.4 vs 37.1%;
40% of the crude mortality in ICU patients with pneumonia was attributable to the
infection. Infected patients stayed an additional 5.8 days in the ICU and 6.7
days in the general ward. Costs of additional stay and antibiotics accounted for
18.6% of the ICU budget. The incidence of nosocomial pneumonia was lower than
expected, despite occupancy exceeding bed capacity, low nurse:patient ratios, and
extensive reuse of disposable respiratory therapy equipment. Nevertheless,
nosocomial pneumonia imposes a significant financial burden on the already scarce
resources available for intensive care in developing countries like India.
PMID- 9651860
TI - Detection of persistent vegetative bacteria and amplified viral nucleic acid from
in-use testing of gastrointestinal endoscopes.
AB - Hospital-acquired infection attributed to inadequate decontamination of
gastrointestinal endoscopes prompted an in use evaluation of recommended
procedures. Specimens were obtained from the internal channels of 123 endoscopes
before, during and after decontamination by flushing with saline and brushing
with a sterile brush, and examined for vegetative bacteria by broth and plate
culture. Four endoscopy units were tested; the chemical disinfectants used were:
2% glutaraldehyde in Centres 1 and 2 (automated) and Centre 3 (manual); peracetic
acid in Centre 4 (automated). Samples from patients in Centre 1 with known
chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human
immunodeficiency virus (HIV-1) infection were also examined for viral nucleic
acid by ultracentrifugation, nucleic acid extraction, reverse transcription (for
RNA) and polymerase chain reaction (PCR). No persistent vegetative bacteria were
found following standard manual cleaning and disinfection for 20 min in 2%
glutaraldehyde in Centres 2 and 3 (N = 37). At Centre 1, while plate culture
yielded no growth, 34% of samples (10/29) grew vegetative bacteria in broth
culture after cleaning and disinfection for 20 min in 2% glutaraldehyde.
Investigation revealed an error in manual cleaning; no bacteria were detected in
37 samples taken after this was corrected. At Centre 4, despite the use of
peracetic acid as a sterilant, three out of 20 (15%) of post decontamination
samples grew bacteria; one contained persistent bacteria. HBV and HCV PCR
analysis detected viral nucleic acid in three out of four and four out of six
samples from viraemic patients undergoing endoscopy in Centre 1 during the period
of improper manual washing. After proper cleaning was instituted, samples from
nine out of nine HCV viraemic patients were negative. HIV RNA was detected in
five of 14 samples taken from endoscopes after use on HIV positive patients but
all post decontamination samples were negative. Detection of bacteria in washes
from endoscope channels is a useful warning of a breakdown in decontamination
practice. Inadequate brushing of internal channels may result in persistent HCV
and HBV viral nucleic acid, the significance of which is not clear. These results
reinforce the importance of adequate manual cleaning of endoscopes before
chemical disinfection.
PMID- 9651861
TI - Screening medical students for MRSA.
PMID- 9651862
TI - Computerized detection of re-admission of patients with MRSA.
PMID- 9651863
TI - Effects of poly(vinylpyrrolidone) and ethylcellulose on alginate microspheres
prepared by emulsification.
AB - Calcium alginate microspheres were prepared by an emulsification process. The
effects of two co-polymers, namely poly(vinylpyrrolidone) and ethylcellulose, on
the properties of the microspheres were studied. Microspheres prepared with and
without poly(vinylpyrrolidone) were spherical and discrete. The microspheres
containing poly(vinylpyrrolidone) exhibited a better flow property but the drug
content was lower and the drug release rate higher. The method of incorporating
poly(vinylpyrrolidone) was found to (significantly) affect the size distribution
and drug content of the microspheres. Ethylcellulose produced marked aggregation
of the microspheres which also showed a lower drug content, but a slower drug
release. The retardation in drug release was attributed to the formation of
aggregated microspheres with a less permeable matrix. The addition of triethyl
citrate, which is a water-soluble plasticizer, was found to increase the rate of
drug release while the use of a higher viscosity grade of ethylcellulose produced
the opposite effect. Ethylcellulose improved the flowability of the microspheres
to a greater extent than poly(vinylpyrrolidone).
PMID- 9651864
TI - Changing the pH of the external aqueous phase may modulate protein entrapment and
delivery from poly(lactide-co-glycolide) microspheres prepared by a w/o/w solvent
evaporation method.
AB - The milk model protein, beta lactoglobulin (BLG), was encapsulated into
microspheres prepared by a multiple emulsion/solvent evaporation method. The
effect of the pH of the outer aqueous phase on protein encapsulation and release
as well as on microsphere morphology has been investigated. At all tested pH
values, the encapsulation efficiency was shown to decrease with increasing the
initial amount of BLG. This was correlated with the reduced stability of the
primary emulsion as the initial BLG increased. In addition, reducing the
solubility of BLG in the external aqueous phase by decreasing the pH to the
isoelectric point of BLG (pI 5.2) resulted in an improved protein encapsulation.
Moreover, it was shown that combining pH modification and optimal stability of
the first emulsion yielded microspheres with a high encapsulation efficiency.
However, release kinetic studies revealed that a significant burst release was
observed with microspheres loaded with large amounts of BLG, especially when
prepared in a medium at pH 5.2. This burst effect was attributed to morphology
changes in the microsphere surface which was characterized by the presence of
pores or channels able to accelerate the release of BLG. These pores were assumed
to result from the presence of large amounts of protein molecules on the
microsphere surface, that aggregate during microsphere formation at pH 5.2.
Indeed, single adsorption experiments have shown that BLG had a higher affinity
for the particle surface when the pH was close to the pI. Thus, reducing the
solubility of a protein in the external aqueous phase allows the product of
microspheres with a better encapsulation efficiency, although this benefit is
provided by a strong adsorption of the protein on microsphere surface.
PMID- 9651865
TI - Clonazepam microencapsulation in poly-D,L-lactide-co-glycolide microspheres.
AB - The work is aimed at the preparation and characterization of biodegradable
microspheres of poly-D,L-lactide-co-glycolide (PLGA), for the controlled release
of clonazepam. The solubility characteristics of this drug make it an interesting
example to evaluate the performances of the two most widely used
microencapsulation techniques, emulsification solvent evaporation and spray
drying. Several biodegradable PLGA copolymers have been evaluated (RG 502H, RG
503H, RG 503, Boerhinger Ingelheim). They differ in terms of molecular weight and
physico-chemical characteristics. The microspheres obtained have been
characterized for their morphology, physico-chemical properties (DSC) and in
vitro dissolution behaviour. Between the two preparation methods, only spray
drying was suitable for the microencapsulation of clonazepam in PLGA
microspheres. In vitro dissolution tests highlight that more sustained release of
drug is achieved with the higher (molecular weight) polymer.
PMID- 9651866
TI - Preparation and in vitro dissolution profile of dual polymer (Eudragit RS100 and
RL100) microparticles of diltiazem hydrochloride.
AB - A microparticulate dosage form for a highly soluble drug, diltiazem
hydrochloride, was formulated with Eudragit RS100 and RL100 using a novel dual
polymer technique. A mixture of diltiazem with Eudragit RS100 (low water
permeability) in acetone was coacervated into soft polymer microdrops, following
which a mixture of diltiazem and RL100 (high water permeability) was added to
produce microparticles consisting of both polymers with diltiazem dispersed in
the matrix. A second formulation was developed using the same method except using
Eudragit RS100 for both steps. For a comparative study, diltiazem, Eudragit RS100
and RL100 were combined together in a single matrix and formulated into
microparticles. In vitro drug release profiles using USP paddle dissolution
apparatus 2 revealed that dual polymer matrix microparticles containing Eudragit
RS100 in the inner and Eudragit RL100 in the outer core exhibit a suitable
release profile with an initial release of the drug followed by a plateau level
for the test period of 5 h. Differential scanning calorimetric analysis showed no
interaction of the drug with the polymers.
PMID- 9651867
TI - Polyamide microcapsules containing alginic acid: extractability of metal ions and
surface characterization by XPS.
AB - Polyamide microcapsules containing alginic acid as a water-soluble macromolecular
ligand (Alg-MC) were prepared by the interfacial polycondensation of
sebacoyldichloride with hexamethylenediamine in a w/o emulsion system. The mean
diameter of the microcapsules was 1.2 microns. The extractabilities of Cu(II),
Ni(II), Co(II) and Ag(I) into the Alg-MC were examined and the highest uptake was
found for Cu(II). It was ascertained that not only the inner ligand solution but
also the membrane can accumulate the metal ions. The surface composition of the
microcapsules was characterized by X-ray photo-electron spectroscopy (XPS) and it
was found that some functional groups of alginic acid were present at the surface
penetrating the membrane.
PMID- 9651868
TI - Production and antiproliferative activity of liposomes containing the antitumour
drug chromomycin A3.
AB - In the present paper the production and characterization of liposomes are
described as a specialized drug delivery system for chromomycin. Liposomes were
prepared by the reverse phase evaporation technique followed by extrusion through
polycarbonate filters; afterwards the vesicles were characterized in terms of
dimensions, morphology and encapsulation efficacy. The aim of this work was to
produce a drug delivery system able to reduce the toxicity problems related to
the administration of this drug. The analysis of the in vitro antiproliferative
activity on cultured human leukemic K562 cells demonstrated that ionic and
neutral liposomes containing chromomycin are 1.5 and 7-fold more effective
respectively as compared to the free drug. Based on these results and taking into
account the increased solubility of the drug in this system, liposomes could
represent a promising drug delivery system for use in the experimental therapy
using chromomycin.
PMID- 9651869
TI - Liposomes containing boronophenylalanine for boron neutron capture therapy.
AB - In the present work, liposomes loaded with Boronophenylalanine (BPA), with or
without stabilization, were formulated for the application in boron neutron
capture therapy. BPA was encapsulated into liposomes as a complex with fructose,
but also as a free drug in two different pH buffers. The influence of critical
variables (cholesterol content, drug:lipid molar ratio, osmotic stress of
liposomes containing hyperosmotic drug solution) on liposome morphology and drug
content was evaluated. The drug content and dissolution profile of different BPA
loaded liposomes were also studied. The physical stability of liposomes in terms
of changes in the size distribution in different osmotic pressure buffers and the
chemical oxidation of phospholipids during storing conditions were investigated.
The encapsulation efficiencies of all formulations were always satisfactory,
being between 20-48%; even when the liposomes were exposed to high osmotic
stress, the particle size was below 200 nm. The BPA-fructose complex loaded
liposomes showed a slower drug release profile.
PMID- 9651870
TI - Study of azathioprine encapsulation into liposomes.
AB - The factors influencing the encapsulation of azathioprine (AZA) into liposomes
were investigated to find out the conditions for its optimal entrapment. Similar
studies for comparison were also carried out on 6-mercaptopurine (6-MP), of which
AZA is a prodrug. AZA and also 6-MP show higher encapsulation efficiencies in
MLVs as compared to LUVs. Variation in phospholipid composition does not seem to
affect the loading capacity of either of the two drugs. The encapsulation
efficiency of both the drugs improves upon addition of cholesterol in the
bilayer, but the effect is seen only up to 30% cholesterol. Thereafter the effect
becomes constant. AZA shows better incorporation in the positively charged
liposomes as compared to those with neutral or negative charge. The entrapment of
6-MP is, however, found to be independent of the charge on the liposomes.
Entrapment efficiency for both the drugs markedly depends on the pH of the
hydration medium, yielding better entrapment efficiencies at high pH values. The
rise in solute concentration initially causes increase in the entrapment of the
two drugs which is followed by a decreasing phase.
PMID- 9651871
TI - Bovine serum albumin loaded poly(lactide-co-glycolide) microspheres: the
influence of polymer purity on particle characteristics.
AB - To study the influence of polymer purity on microsphere characteristics, bovine
serum albumin (BSA) loaded biodegradable microspheres were prepared by spray
drying using two samples of poly(lactide-co-glycolide), PLG, (50:50, mwt = 35 and
69 kDa). Polymer properties were varied by DL-lactide and glycolide addition or
by ultrafiltration. While the effective drug loading was not affected by polymer
purity, Tg was decreased with increasing monomer and oligomer content. The
removal of these low molecular weight substances by ultrafiltration led to a
narrower molecular weight distribution compared to the untreated PLG. Concerning
the polymer with the higher molecular weight, microsphere morphology was also
strongly affected by polymer composition. In contrast to the non-modified PLG,
monomer addition yielded particles with a much smoother surface structure.
Moreover, in vitro cytotoxicity of the microspheres prepared from the polymer
pretreated by ultrafiltration was significantly reduced, whereas monomer addition
caused a dramatic decrease of cells surviving contact with the microsphere
extract. The in vivo degradation rate of the ultrafiltered microspheres was
decreased and as a result, protein release at later times was slowed down.
Furthermore, depending on the effective drug loading level, monomer addition
resulted in a decrease in the initial protein burst. It can be concluded that the
effect of low molecular weight impurities in a polymer on microsphere
characteristics and on cytotoxicity cannot be ignored. Their elimination is
possible by ultrafiltration.
PMID- 9651872
TI - Preparation of polylactic acid microcapsules containing ciprofloxacin.
AB - Microcapsules have been used as drug delivery systems in the pharmaceutical field
for sustained or controlled release of drug, and for artificial cells and organs.
Biodegradable polymers, especially polylactic acid, have been widely used in this
field. In this study, an attempt was made to develop a new method to prepare
polylactic acid microcapsules for drug delivery. The biodegradable polylactic
acid microcapsules were made by the phase separation process: two types of
polylactic acid, poly[(D,L)lactic acid] and poly[(L)lactic acid] were combined as
the membrane material. Because of the difference of the crystal properties of the
two polymers, the aggregation which happens frequently in the phase separation
process was prevented. As a model drug, Ciprofloxacin was encapsulated in the
polylactic acid microcapsules.
PMID- 9651873
TI - Comments on 'Modulation of protein release from chitosan-alginate microcapsules
using the pH-sensitive polymer hydroxypropyl methyl cellulose acetate succinate'.
PMID- 9651874
TI - Prevalence and natural history of periodontal disease in prehistoric Scots (pre
900 AD).
AB - The periodontal status of a Scottish prehistoric population was studied. No
individual over the age of 10 yr had an entirely healthy periodontium. Gingivitis
was the most widespread disease state in the adolescent and younger age groups.
The progression towards periodontitis was at a constant rate and mirrored modern
epidemiological studies. A small proportion of individuals proved to be either
more susceptible or resistant to periodontal disease. There was no evidence of
periodontal disease prevalence being higher than that of modern societies with
access to dental treatment. Much can be learnt regarding the natural history of
periodontal disease by the study of archaeological material.
PMID- 9651875
TI - Accuracy of quantitative digital subtraction radiography for determining changes
in calcium mass in mandibular bone: an in vitro study.
AB - The aim of this in vitro study was to determine the accuracy of digital
subtraction radiography (DSR) to detect small changes in calcium mass in alveolar
bone adjacent to tooth roots. In each of 4 dried porcine mandible segments, one
interproximal and one buccal "defect" region was defined adjacent to a premolar
root. A series of cortical and cancellous bone slices with a 50 microns--stepwise
increasing thickness (0-5000 microns) were attached to the mandible segments
covering the respective "defect" region. Standardized radiographs were
quantitatively assessed for density changes using DSR. After dissolving each bone
slice in hydrochloric acid, its calcium concentration was photometrically
determined. For each bone slice, the mean calcium mass covering a single pixel of
the subtraction image was calculated. The Wilcoxon signed-rank test and the Mann
Whitney U-test were used for statistical analysis (alpha = 0.05). A strong linear
correlation (r2 = 0.86-1.00; p < or = 0.001) was found between the thickness of
the bone slices and their calcium mass. Cortical bone showed a 3.5 times higher
mean calcium mass/pixel than cancellous bone. Furthermore, a strong linear
correlation (r2 = 0.63-1.00; p < or = 0.001) was found between the mean calcium
mass per image pixel and the radiographic density changes. Neither the bone type
nor the "defect" localization had a significant influence on radiographic density
changes caused by changes in calcium mass. A change in mean calcium mass per
image pixel of 0.1-0.15 mg was necessary to be detected by DSR. In conclusion,
this study revealed a high accuracy of DSR to detect small changes in calcium
mass in alveolar cortical and cancellous bone.
PMID- 9651876
TI - The effects of cold storage and endotoxin challenge on osteoblast viability and
interleukin-6 production.
AB - Autogenous hip marrow is an excellent source of pluripotential cells for
regenerative procedures. However, before this treatment modality can be employed
a method to attenuate osteoclast activity must be developed. The shock of cold
storage (4 degrees C) is thought to abate osteoclast activity through the
downregulation of osteolytic cytokines produced by osteoblasts. The objective of
this study was to evaluate the effects of cold storage (4 degrees C) and
endotoxin challenge on bone cell culture viability and interleukin-6 (IL-6)
production. These cells (osteoblasts) were primarily harvested from murine
calvaria utilizing sequential digestions, separated by density gradient and
combined. Twelve-well cell culture plates were inoculated with 2 x 10(4) cells/ml
and placed in cold storage for 1-14 d. After cold storage the cultures were then
incubated at 37 degrees C for 1-20 d. A set of replicate plates was also
challenged with 10 ng/ml endotoxin upon incubation at 37 degrees C for 4
consecutive days. Cells were evaluated daily for alkaline phosphatase activity.
Cell culture supernatants were also collected daily and batch assayed for IL-6
production. Cell cultures did not survive more than 48 h of cold storage. There
was a decrease in IL-6 secretion in all refrigerated cultures and a significant
decrease in those cells refrigerated for 48 h versus control cultures (p < 0.05).
Replicate cultures treated with endotoxin secreted significantly increased
amounts of IL-6 in both the control cultures and the cultures exposed to 24 h of
cold storage versus non-endotoxin-treated control cultures (p < 0.05). These
observations suggest that after 48 h of cold storage autogenous marrow may be
safe to use because of the dramatic decrease in IL-6 production by osteoblasts.
PMID- 9651877
TI - Evidence for healing of interproximal intrabony defects after conventional and
regenerative therapy: digital radiography and clinical measurements.
AB - In 24 patients with advanced periodontitis 38 interproximal intrabony defects
were treated by conventional surgery (C; n = 8) or guided tissue regeneration
(GTR) using expanded polytetrafluoroethylene (G; n = 17) or Polyglactin 910
barriers (V; n = 13). Presurgically (BL), 6 and 12 months postsurgically clinical
parameters (GI, PII, PPD, PAL-V) and 36 standardized radiographs were obtained
generating 72 pairs (36 BL/6 months; 36 BL/12 months). Using linear measurements
on the radiographs and subtraction analysis, bony fill within the defects was
assessed. Intrasurgically the extension of the intrabony defects was measured.
Statistically significant (p < 0.05) attachment gain was found after 6 (C: 2.4 +/
1.6 mm; G: 3.2 +/- 1.6 mm; V: 3.4 +/- 1.5 mm) and 12 months in all groups (C:
2.4 +/- 1.7 mm; G: 3.1 +/- 1.7 mm; V: 4.0 +/- 1.7 mm). Thirty-nine of 72 pairs of
radiographs were unsuitable for subtraction analysis. Significant (p < 0.05) bony
fill was observed at 6 (C: 0.3 +/- 1.0 mm; G: 0.7 +/- 1.2 mm; V: 0.9 +/- 1.2 mm)
and 12 months (C: 0.0 +/- 1.1 mm; G: 1.4 +/- 1.5 mm; V: 1.5 +/- 1.7 mm) only
after GTR surgery. GTR therapy yielded significantly more bony fill than
conventional surgery 12 months postsurgically (p < 0.1). Bony fill (linear
measurement) was influenced by age, smoking, baseline bone loss and PAL-V gain (p
< 0.0001). Significantly more radiographs taken with potentially unstable support
of the filmholder were not suitable for subtraction analysis than those with
stable support (p < 0.05). Bony gain (subtraction analysis) was positively
modulated by bony fill (linear measurement) and use of biodegradable barriers (p
= 0.002). There is a correlation between PAL-V gain and bony fill (linear
measurement). Smoking impairs attachment gain and bony fill. Potentially stable
support of the filmholder provided radiographs suitable for subtraction analysis.
PMID- 9651878
TI - Evidence that cyclosporin A administration induces the formation of new cementum
like islets inside the gingival connective tissue.
AB - Two groups of 3 male Sprague-Dawley rats were given orally 30 mg/kg/d of vehicle
(control group) or cyclosporin-A (experimental group) solution for 14 wk. The
rats were anesthetized, tissues fixed by intracardiac perfusion of fixative
solution and jaws dissected, demineralized, processed for Epon inclusion and cut
by semi-thin serial sections. Histological examination revealed the presence of
several islets located paravascularly inside the gingival connective tissue in
the proximity of the root surfaces. The structure of these new cementum-like
islets (NCLIs) was either compact and homogeneous or heterogeneous, but identical
to that of the adjacent new cementum (NC) deposits. Histomorphometric evaluation
indicated that the volume and the external surface of the NCLIs varied from 2354
to 679,497 micron 3 and from 465 to 47,517 micron 2, respectively. These
observations (a) suggest that CsA stimulates possibly paravascular progenitor
cells which secrete in situ a NC-like material and (b) provides further evidence
about the high potential of CsA to induce NC formation.
PMID- 9651879
TI - A digital subtraction radiography investigation of upper first molar proximal
bone density changes in adolescents.
AB - The aim of this in vivo study was to investigate the ability of digital
subtraction radiography to monitor changes in proximal bone density, adjacent to
the upper first molars, in a group of adolescents using the Digora direct digital
radiographic system to acquire images. For 57 adolescents, assessments of changes
in probing attachment level at the mesio- and disto-buccal surfaces of both upper
first molars and proximal crestal bone density using digital subtraction
radiography were made. At the conclusion of this 21-month study attachment loss
was identified in 34 (17%) of the 204 sites analysed. For sites with attachment
loss a mean decrease in bone density equivalent to 5.51 mm3 aluminium (Al) was
found compared to 2.96 mm3 Al for those without (p < 0.001). For the 17 subjects
with attachment loss a mean equivalent to 4.66 mm3 Al was lost from the crestal
bone compared with 2.56 mm3 Al for the 40 subjects without attachment loss (p <
0.01). The correlation between attachment loss and bone density changes was poor
for both sites (r = 0.13), p = 0.067) and mean scores for subjects (r = 0.24, p =
0.069). A visual qualitative assessment of bone density change found that 70.6%
of sites with attachment loss compared to 62.4% of those without had a decrease
in crestal bone density. This study suggests that it is possible to monitor bone
density changes in adolescents, with a developing dentition, using digital
subtraction radiography. Further, it is suggested that conventional probing
assessments of attachment level may underestimate the level of destructive
periodontal disease in this age group.
PMID- 9651880
TI - [3H]5,7-dichlorokynurenic acid recognizes two binding sites in rat cerebral
cortex membranes.
AB - Binding of [3H]5,7-dichlorokynurenic acid ([3H]DCKA), a competitive antagonist of
the strychnine-insensitive glycine site of the N-methyl-D-aspartate (NMDA)
receptor channel complex, was characterized in synaptic plasma membranes from rat
cerebral cortex. Non linear curve fitting of [3H]DCKA saturation and homologous
displacement isotherms indicated the existence of two binding sites: a specific,
saturable, high affinity site, with a pKD value of 7.24 (KD = 57.5 nmol/l) and a
maximum binding value (Bmax) of 6.9 pmol/mg of protein and a second site, with
micromolar affinity. The pharmacological profile of both binding components was
determined by studying the effect on [3H]DCKA and [3H]glycine binding of a series
of compounds known to interact with different excitatory and inhibitory amino
acid receptors. These studies confirmed the identity of the high affinity site of
[3H]DCKA binding with the strychnine-insensitive glycine site of the NMDA
receptor channel complex. 3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloroindole-2
carb oxylic acid sodium salt (GV 150526A), a new, high affinity, selective
glycine site antagonist (1), was the most potent inhibitor of this component of
binding (pKi = 8.24, Ki = 5.6 nmol/l). The low affinity component of [3H]DCKA
binding was insensitive to the agonists glycine and D-serine and the partial
agonist (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA 966), though recognised by
glycine site antagonists. The precise nature of this second, low affinity
[3H]DCKA binding site remains to be elucidated.
PMID- 9651881
TI - PEST sequences in proteins involved in cyclic nucleotide signalling pathways.
AB - There is growing evidence that PEST sequences act as proteolytic recognition
signals within polypeptides. PEST sequences are rich in proline (P), glutamic
acid (E), serine (S), and threonine (T) and can be identified by the PEST-FIND
program. Both the catalytic and regulatory subunits of the cAMP-dependent protein
kinase have been shown to have conditional PEST sequences which are exposed upon
cAMP binding to the enzyme. cAMP binding leads to rapid dissociation of C- and R
subunits, and both subunits have increased sensitivity to proteolysis. It is not
known whether other proteins that participate in the cyclic nucleotide signalling
pathway have PEST regions in their amino acid sequences. Therefore, we have
screened amino acid sequences of proteins that are directly involved in cyclic
nucleotide cascade, including cGMP-dependent protein kinases, anchoring proteins
for cAMP-dependent protein kinase, cyclic nucleotide-gated ion channels, and
cyclic nucleotide phosphodiesterases, for PEST sequences using the PEST-FIND
program. Many PEST sequences with high scores have been identified in these
proteins. The occurrence of the PEST sequences is very high in proteins involved
in cyclic nucleotide signalling pathways (approximately 80%). This value is much
higher than the percentage (10%) of PEST sequences that can be found in the
primary structures of the proteins listed in the data bank. This frequent
occurrence of PEST sequences in proteins involved in cyclic nucleotide action and
metabolism suggests an important role of proteolysis of these key proteins of
signal transduction.
PMID- 9651882
TI - Mapping of dopamine D3 receptor binding site by pharmacological characterization
of mutants expressed in CHO cells with the Semliki Forest virus system.
AB - Nine mutants and the wild-type human dopamine D3 receptor were expressed at high
levels in BHK and CHO cells using the Semliki Forest virus system and were
analysed for receptor binding with several structurally different dopamine D3
ligands. The mutation His349Leu showed a significant decrease in pKi values for
raclopride, dopamine and GR218231, but an increase in affinity for GR99841.
Thr369Val had an increase in pKi for both GR99841 and 7-OH-DPAT. The receptor
modelling based on sequence alignment with bacteriorhodopsin indicated that
Thr369 and His349 are located on the inside of the ligand binding pocket and the
effect of the mutagenesis was therefore expected. The change in binding affinity
for Thr369Val could be due to the location in the transmembrane domain VII close
to the aspartate residue in domain III, the postulated counter ion for dopamine.
PMID- 9651883
TI - Characterization of muscarinic cholinergic receptor subtypes in rat prostate.
AB - The purpose of this study was to characterize the muscarinic receptor subtypes in
the individual lobes of the rat prostate. Immunoprecipitation was performed on
homogenates of these 3 lobes using antibodies to the m1-m4 muscarinic receptor
subtypes. Reverse transcriptase polymerase chain reaction assays (RT-PCR) were
also performed using primers specific for each of the five muscarinic receptor
subtypes (m1-m5). The susceptibility of the receptors to degradation by
endogenous prostate proteases was assessed by mixing rat ventral prostate with
rat heart (m2) and rat parotid (m3) prior to immunoprecipitation. In the ventral
lobe, transcripts for the m1-m4 subtypes were amplified whereas in the dorsal and
lateral lobes only the m2 and m3 sets of primers amplified PCR products of the
predicted size. Immunoprecipitation of the ventral lobe resulted in predominantly
m3 receptors, while the majority of receptors immunoprecipitated from lateral and
dorsal lobes were the m2 subtype. The m3 muscarinic subtype was apparently
susceptible to degradation by prostate proteases whereas the m2 subtype was not.
These results demonstrate a regional distribution in the subtypes of muscarinic
receptors in the rat prostate, and a greater susceptibility of the m3 receptor to
degradation during immunoprecipitation than the m2 subtype.
PMID- 9651884
TI - Redox regulation of signal transduction in smooth muscle cells: distinct effects
of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase.
AB - Reactive oxygen species function as signaling molecules, and are known to be
generated under both normal and pathological conditions. Using vascular smooth
muscle cells, we have demonstrated an increase in mitogen activated protein
kinase activity in response to oxidants. Mitogen activated protein kinase
activity increased linearly with time in cells treated with pervanadate. Hydrogen
peroxide also caused rapid induction of mitogen activated protein kinase. Protein
kinase C down regulation partially decreased induction of mitogen activated
protein kinase activity by oxidants, and the Ca2+ ionophore, ionomycin. Protein
kinase C inhibitors, compound-3 and bisindolylmaleimide did not inhibit oxidant
induced mitogen activated protein kinase activity, where as calphostin C
activated it. The tyrosine kinase inhibitors genistein, herbimycin A and
tyrphostin caused 50% inhibition of oxidant induced mitogen activated protein
kinase activation. These results suggest that oxidant-induced mitogen activated
protein kinase is protein kinase C independent.
PMID- 9651885
TI - Strategies for positioning fluorescent probes and crosslinkers on formyl peptide
ligands.
AB - Chemoattractant receptors represent a major subset of the G-protein coupled
receptor (GPCR) family. One of the best characterized, the N-formyl peptide
receptor (FPR), participates in host defense responses of neutrophils. The
features of the ligand which regulate its interaction with the FPR are well
known. By manipulating these features we have developed new ligands to probe
structural and mechanistic aspects of the peptide-receptor interaction. Three
ligand groups have been developed: 1) ligands containing a Lys residue located in
positions 2 through 7 that can be conjugated to FITC (N-formyl-Met1-Lys2-Phe3
Phe4, N-formyl-Met1-Leu2-Lys3-Phe4, N-formyl-Met1-Leu2-Phe3-Lys4, N-formyl-Met1
Leu2-Phe3-Phe4-Lys5, N-formyl-nLeu1-Leu2-Phe3-nLeu4-Tyr5-Lys6 and N-formyl-Met1
Leu2-Phe3-Phe4-Gly5-Gly6-Lys7; 2) fluorescent pentapeptide ligands (N-formyl-Met
X-Phe-Phe-Lys(FITC) where X = Leu, Ala, Val or Gly); and 3) small crosslinking
ligands where the photoaffinity crosslinker 4-azidosalicylic acid (ASA) was
conjugated to Lys in positions 3 and 4 and p-benzoyl-phenylalanine (Bpa) was
located in position 2 in N-formyl-Met1-Bpa2-Phe3-Tyr4. The peptides were
characterized according to activity and affinity in human neutrophils and cell
lines transfected with FPR. All of the peptides were agonists, with parallel
affinity and activity. In the first group, the peptide activity decreases as Lys
is placed closer to the N-formyl group and the activity is improved by 1-3 orders
of magnitude by conjugation with FITC. In the second group, the dissociation rate
of the peptide from the receptor increases as position 2 is replaced by aliphatic
amino acids with smaller alkyl groups. In the third group, crosslinking ligands
remain biologically active, display nM affinity and covalently label the FPR.
PMID- 9651886
TI - Finite element modelling of bulk muscular tissue.
PMID- 9651887
TI - Biomaterials in the 21st century revisited!
PMID- 9651888
TI - Material properties of commonly-used interface materials and their static
coefficients of friction with skin and socks.
AB - Compressive stiffness (CS) of different supporting materials used in prosthetics
and orthotics and their static coefficients of friction (COF) with skin and socks
were characterized. Materials tested included Spenco, Poron, nylon-reinforced
silicone, Soft Pelite, Medium Pelite, Firm Plastazote, Regular Plastazote, and
Nickelplast. A displacement-controlled testing device was constructed to assess
the CS of 11.1 mm diameter material specimens under cyclic loading (1 Hz) to 220
kPa over 10- and 60-min periods. Results demonstrated local CS ranging from 687
kPa (Poron) to 3,990 kPa (Soft Pelite). To fit the cyclic stress-strain (S-S)
data within an error of 4.0 percent full-scale output, the minimum order of fit
required for Spenco, Poron, and nylon-reinforced silicone was a third-order
polynomial; for Soft Pelite, Medium Pelite, Firm Plastazote, and Regular
Plastazote, a second-order polynomial; and for Nickelplast, a linear fit. For all
materials, the nonrecovered strains were related to loading time using an
exponential fit. A biaxial force-controlled load applicator device was used to
assess COF at skin-material, sock-material, and skin-sock interfaces for shear
forces of 1 to 4 N applied to a 10.2 x 7.8 mm loading pad. COFs ranged from 0.48
(+/- 0.05) to 0.89 (+/- 0.09). COFs at skin-material interfaces were
significantly (p < 0.05) higher than those at skin-sock interfaces. There was a
trend of a higher COF at sock-material interfaces than at skin-sock interfaces.
These data are of potential utility in finite element modeling sensitivity
analysis of residual limb-prosthetic socket systems or body-orthosis systems to
characterize effects of material features on interface pressure and shear stress
distributions.
PMID- 9651889
TI - Mechanical efficiency during gait of adults with transtibial amputation: a pilot
study comparing the SACH, Seattle, and Golden-Ankle prosthetic feet.
AB - As more and more prosthetic feet become commercially available, the selection of
the appropriate device is a more difficult task for clinical team members. To
date, ranking prosthetic feet based on biomechanical parameters has been done
using the spring efficiency. The current analytical technique for calculating
spring efficiency has two flaws: first, prosthetic feet with a bendable flexible
keel are analyzed the same way as those with an articulated ankle and a rigid
foot, and second, there is no accounting for the energy losses in the
viscoelastic cosmetic material surrounding the keel. This paper develops a
rigorous technique to calculate the net energy stored or dissipated and then
recovered during the stance phase of gait. Five adults with transtibial
amputation were tested with three different prosthetic feet: SACH, Seattle, and
Golden-Ankle. The subjects walked at self-selected cadence and stepped on a force
plate while two-dimensional segmental kinematic and kinetic data were collected.
The results showed that the Golden-Ankle stored or dissipated and then recovered
significantly more energy than either the SACH or Seattle. The time to reach foot
flat was also significantly reduced for the Golden-Ankle in comparison to both
the others. Because the cosmetic material of the SACH foot can store or dissipate
and then recover as much energy as the Seattle foot, the SACH foot should be
considered an energy-storing foot. Finally, the net efficiency alone can not
discriminate adequately among different types of prosthetic feet; therefore, one
should consider the time to reach foot flat and the amount of energy recovered as
additional objective criteria (weight, maintenance, and cosmesis) for selection
of a prosthetic foot device.
PMID- 9651890
TI - Validation of F-Scan pressure sensor system: a technical note.
AB - This study performed a quantitative validation on a recently developed pressure
sensitive transducer system, the F-Scan sensor system. The results indicate that
the sensor is adequate for determination of pressure distribution under contact
conditions with soft materials. The linear response of the sensor was up to 1.7
MPa with good homogeneity throughout sensor cells. However, the sensor is
sensitive to surface conditions, loading speeds, and temperature. Variations also
exist from sensor to sensor. In order to have accurate measurement, calibration
was recommended in actual clinical or experimental conditions prior to use,
including surface contact conditions, loading speeds, and temperature
environment. In addition, this sensor system is not suitable for hard surface
contact such as plexiglas.
PMID- 9651891
TI - Sensing stability and dynamic response of the F-Scan in-shoe sensing system: a
technical note.
AB - The objective of this study was to gain a better understanding of the F-Scan to
determine its appropriate clinical application. Vertical pressure was applied to
a sensor foil over the range of 10-80 kPa with or without the intervention of 0.2
0.8 mm thick felt. Sensor sensitivity reached a maximum without the felt, and
decreased with increasing felt thickness, stabilizing at 48-74% of the maximum
level when felt thickness exceeded 0.4 mm. This sensitivity change was caused by
the slight difference in thickness of sensing areas from that of non-sensing
areas. Dynamic response time was delayed by a mean of 0.32 s. Although the cause
of this dynamic response delay remains unclear, it was considered to be
inappropriate for accurate dynamic measurements. Therefore, rather than using F
Scan measurement to accurately obtain actual values, it should be used for
relative comparisons of the plantar pressure distributions under constant
conditions.
PMID- 9651892
TI - Methods for reducing energy dissipation in cosmetic gloves.
AB - For cosmetic reasons, hand prostheses are provided with cosmetic gloves. Their
pleasing appearance, however, is accompanied by poor mechanical behavior,
resulting in a negative influence on prosthesis operation. Glove stiffness is
high and nonlinear, and internal friction in the glove material causes energy
dissipation (hysteresis). In this article, two methods for reducing hysteresis in
cosmetic gloves are proposed, that may be applied independently or in
combination. Glove modification. Altering the mechanical properties of the glove
itself is the first method that is presented. It was found possible to reduce
both stiffness and hysteresis about 50% by forming grooves into the inside of the
glove. Together with the evaluation of this method, several properties of the
cosmetic glove were determined. Motion optimization. Additionally, a second
method for reducing hysteresis was developed. The amount of hysteresis is
influenced by the way the glove is forced to deform. The prosthesis mechanism,
determining this deformation, was designed for minimum hysteresis and maximum
cosmesis. For the prosthesis-glove combination used in this study, thumb motion
optimization reduced hysteresis by about 65%.
PMID- 9651893
TI - Kinematic characterization of wheelchair propulsion.
AB - Rehabilitation scientists and biomedical engineers have been investigating
wheelchair propulsion biomechanics in order to prevent musculoskeletal injuries.
Several studies have investigated wheelchair propulsion biomechanics; however,
few have examined wheelchair propulsion stroke patterns. The purpose of this
study was to characterize wheelchair propulsion stroke patterns by investigating
joint accelerations, joint range of motions, wheelchair propulsion phases, and
stroke efficiency. Seven experienced wheelchair users (5 males, 2 females) were
filmed using a three-camera motion analysis system. Each subject pushed a
standard wheelchair fitted with a force-sensing pushrim (SMARTWheel) at two
speeds (1.3 and 2.2 m/s). The elbow angle was analyzed in the sagittal plane,
while the shoulder joint was analyzed in the sagittal and frontal planes. Three
distinctly different stroke patterns: semi-circular (SC), single looping-over
propulsion (SLOP), and double looping-over-propulsion (DLOP), were identified
from the kinematic analysis. Through our analysis of these patterns, we
hypothesized that SC was more biomechanically efficient than the other stroke
patterns. Future studies using a larger number of subjects and strokes may reveal
more significant distinctions in efficiency measures between stroke patterns.
PMID- 9651894
TI - Polyurethane foams: effects of specimen size when determining cushioning
stiffness.
AB - Polyurethane (PU) foams are used as inexpensive materials for reducing interface
pressure in a number of rehabilitative applications, particularly seating and
prosthetic limb interfaces. Specimens of three different PU foams were cut to
four different sizes and compressed according to ASTM protocols to determine
their stiffness capabilities. It was found that the test results varied according
to the relationship between the size of the test specimen and the test indenter.
It is recommended that investigators create a testing situation that reflects
their application when determining the cushioning capabilities of these
materials.
PMID- 9651895
TI - Assessment of alternating air mattresses using a time-based interface pressure
threshold technique.
AB - Laboratory evaluation techniques for support surfaces have centered largely
around interface pressure (IP) measurement, typically analyzing discrete maximum
and minimum levels, or calculating the average pressure. Nowadays, alternating
pressure air mattresses (APAMs) are used increasingly for the prevention and
treatment of pressure sores. Pressure relief (PR) provided by an APAM is time
varying. A computerized system that measures IP, air pressure, and pressure-time
characteristics of dynamic support surfaces has been developed for performance
assessment. Using this system, IP was recorded continuously and the durations of
pressures below three thresholds (30, 20, and 10 mmHg) were calculated
automatically. Fifteen sound volunteers were used to evaluate the pressure
relieving characteristics of four APAMs, including one overlay. Results indicated
significant differences (p < 0.001) between products when durations below 20 and
10 mmHg thresholds were analyzed, showing some devices were only capable of
momentarily relieving pressure. Maximum contact pressures on the sacrum were
significantly lower (p < 0.0001) on devices where inflation pressure was adjusted
according to the body mass of the subject. With further clinical validation, this
tool could assist in the selection of alternating surfaces of any description.
PMID- 9651896
TI - The relationship between gait parameters and pain in persons with transtibial
amputation: a preliminary report.
AB - This is a preliminary study of the potential relationship between pain and gait
parameters in 11 persons with transtibial amputation who underwent gait analysis
under both baseline and discomfort walking conditions. Gait analysis included
measurement with a VA-Rancho Stride Analyzer of the following gait parameters:
velocity, cadence, stride length, gait cycle, and support time. These data were
correlated with pain intensity data determined with a standard Visual Analog
Scale. Wide ranges of discomfort were reported and corresponding alterations in
gait parameters varied greatly in both magnitude and quality. There was no
obvious pattern in acclimation to discomfort. A significant correlation was found
between pain intensity and the magnitude of change in velocity (p < 0.05). In
addition, all subjects reporting significant pain (> 33% of maximum) slowed down,
while gait alterations of others varied widely in response to the experience of
pain. Further studies with a larger and more homogeneous subject pool to examine
these relationships fully are recommended to follow this preliminary report.
PMID- 9651897
TI - An assistive device for persons with severe amnesia.
AB - Five persons with severe amnesia were trained to use a device containing items of
information relevant to daily activities. The training consisted of a procedure
in which requests for information were paired with a tone, and the subject was
required to access the device and respond with the answer to the request. The
tone was gradually faded, with the goal of having the subject respond to a
question alone. All of the subjects learned to consistently access the device and
provide correct responses following a request for information. Generalization
across requesters and settings in which the requests were made was also achieved.
The findings are discussed in regard to the utility of exploiting the relatively
well-preserved procedural memory system for rehabilitation of persons with severe
amnesia.
PMID- 9651898
TI - A validation study on status and age of natural menopause reported in the E3N
cohort.
AB - The accuracy of self-reported menopausal status and age at menopause has been
analysed in a validation study using the gynecologist's medical records as the
reference. Concordance between the two sources for menopausal status was assessed
in 151 women. The kappa coefficient obtained was 0.85 (95% CI, 0.69-1.00).
Agreement on age at menopause was tested in 57 women and the kappa coefficient
obtained was 0.64 (95% CI, 0.34-0.94). Age at menopause was accurately reported
by 32% of the subjects. This percentage increased to 69 and 86% when agreement
within 1 and 2 year(s) was considered, respectively. These results suggest that
women can provide data on their natural menopause history with sufficient
accuracy to test some hypotheses associating this event with the evolution of
their health status.
PMID- 9651899
TI - Association of diet and other lifestyle with onset of menopause in Japanese
women.
AB - OBJECTIVES: To evaluate the cross-sectional relationships of dietary and other
lifestyle variables to menopause. METHODS: A total of 4186 female residents aged
45-55 in Takayama City, Japan, responded to a self-administered questionnaire
(the response rate was 89.3%). Diet in the past year was assessed by
semiquantitative food frequency questionnaire. Using the logistic regression
model, associations between study variables and menopausal status were estimated
in terms of odds ratio (OR). RESULTS: Nulliparity and lower relative weight were
significantly associated with menopause after controlling for age (P < 0.05). The
association of smoking with menopause was marginally significant after
controlling for age (P = 0.06). Higher intakes of fat, cholesterol, and coffee
were inversely and significantly associated with later menopause after
controlling for age, total energy, parity, menarche age, and relative weight (ORs
for the highest tertiles of fat, cholesterol and coffee intakes were 0.78, 0.79,
and 0.70, respectively, P < 0.05). The highest tertiles of calcium and soy
product intakes were significantly associated with menopause after controlling
for the covariates (ORs = 1.25 and 1.42, respectively, P < 0.05), but
postmenopausal women who had menopause at later age showed higher calcium intake
than those who had menopause at early age. CONCLUSION: Dietary factors appear to
be associated with onset of menopause.
PMID- 9651900
TI - Menstrual cycle length preceding menopause in relation to age at menopause.
AB - OBJECTIVES: In one of the earlier hypotheses of the etiology of breast cancer
(Korenman's 'oestrogen window' hypothesis (1981)), it was assumed that women with
a later age at menopause have a longer period with irregular cycles preceding
menopause than women with an early menopause. This assumption was tested in a
prospective study. METHODS: Subjects were 628 women, born between 1932 and 1941,
who had participated in a breast cancer screening project in Utrecht, The
Netherlands (the DOM-project) in 1982-1985, and who were still menstruating at
that time. The women had filled out a questionnaire and a menstrual calendar
every 2 years to determine their age at menopause prospectively. The women had
not used oral contraceptives or medicines for menopausal complaints and had
reached natural menopause by 1992. The median of the mean menstrual cycle length
per woman and the median of the standard deviation of the mean menstrual cycle
length per woman were plotted against number of years prior to menopause in three
categories of age at menopause (44-49; 50-54; 55-59). RESULTS: During the 9 years
prior to menopause, women with a late age at menopause have a somewhat higher
mean menstrual cycle length than women with a younger age at menopause (P =
0.0008). Cycle length variability in the 9 years prior to menopause is not
statistically significantly different between the three categories of age at
menopause (P = 0.16). CONCLUSIONS: The assumption that women with a late age at
menopause have a longer period with irregular cycles than women with an earlier
age at menopause was not corroborated by our results.
PMID- 9651901
TI - Duration of hormonal replacement therapy in general practice; a follow-up study.
AB - OBJECTIVES: To assess the mean duration of use of HRT in general practice and to
identify determinants of the duration of HRT use. METHODS: A general population
of 1689 women aged 45-60 years and enlisted in five group practices of general
practitioners were followed for 9 months to trace first HRT prescriptions. All
103 women who were prescribed HRT were followed for a period of 2.25 years.
Duration of HRT was assessed by using the data provided on the dispensing of HRT.
Possible determinants of duration of use, such as attitude towards menopause,
menopausal status and another six variables were measured by means of a
questionnaire. RESULTS: None of the 103 women received HRT for a preventive
purpose; the main indication was menopausal complaints. More than 60% of the
women stopped their HRT within 6 months and only 8% of the women remained on HRT
for more than 2 years. The mean duration of use was 7 months. Determinants that
significantly predicted the duration of HRT use were age, attitude towards
treatment of the menopause and the group practice. CONCLUSIONS: The mean duration
of HRT use is very short, despite the fact that the most prevalent indication is
the alleviation of menopausal symptoms. Apparently, Dutch women are presently
unwilling to take HRT for longer periods.
PMID- 9651902
TI - The effect of hysterectomy and endometrial ablation on follicle stimulating
hormone (FSH) levels up to 1 year after surgery.
AB - OBJECTIVES: In this study the hypothesis was tested, that in premenopausal
patients FSH-levels would rise after 'simple hysterectomy'. As endometrial
ablation is not supposed to compromise ovarian bloodflow, there would be no such
change in ablated patients. METHODS: Between January 1995 and April 1996,
consecutive premenopausal patients with dysfunctional uterine bleeding who were
scheduled for hysterectomy or endometrial ablation were asked to participate in
the study. Bloodsamples were drawn before surgery, six weeks, six months and one
year after surgery. FSH and oestradiol (E2) were assayed. In all patients data
about length and weight were collected to calculate Body Mass Index (BMI). Every
visit patients filled in a questionnaire, containing questions about typical
climacteric complaints, combined in a five-point scale. RESULTS: Except for a
significant difference in preoperative FSH-level between both groups, there were
no significant differences regarding age, Body Mass Index (BMI), oestradiol (E2)
or the percentage of women with vasomotor complaints. Compared to the
preoperative starting level, six weeks, six months and one year after surgery a
significant rise in serum FSH in the hysterectomy group, as well as in the
ablation group was found. However there was no significant difference in FSH
increase between both groups. One third of the patients in both groups had
typical climacteric complaints as flushing and nocturnal sweating. CONCLUSIONS:
Assaying serum FSH-levels before and after uterine surgery and comparing
hysterectomized patients and patients after endometrial ablation, we found a
significant rise in FSH-level up to one year after surgery in both groups
postoperatively, indicating impaired ovarian function. There was no difference in
FSH-levels between both groups. Therefore major uterine surgery (hysterectomy,
ablation) may prelude an earlier onset of menopause.
PMID- 9651903
TI - Physical exercise and vasomotor symptoms in postmenopausal women.
AB - BACKGROUND: The mechanisms causing postmenopausal vasomotor symptoms are unknown,
but changes in hypothalamic beta-endorphins have been suggested to be involved.
beta-endorphin production may be increased by regular physical exercise.
OBJECTIVE: To assess if physically active women suffered from vasomotor symptoms
to a lower extent than sedentary women. MATERIAL AND METHODS: All women (n =
1323) in the ages ranging from 55-56 years in the community of Linkoping Sweden,
were included. In a questionnaire these women were asked about their physical
exercise habits and their complaints from vasomotor symptoms. Only those 793
women who had reached a natural menopause were grouped into sedentary, moderately
or highly active women, based on a physical activity score. RESULTS: Only 5% of
highly physically active women experienced severe hot flushes as compared with 14
16% of women who had little or no weekly exercise (P < 0.05; relative risk 0.26;
CI 95%: 0.10-0.71). This was not explained by differences in body mass index,
smoking habits or use of hormone replacement therapy. Women who used hormone
replacement therapy were more physically active than non-users (P < 0.05).
CONCLUSION: Fewer physically active women had severe vasomotor symptoms compared
with sedentary women. This may be due to a selection bias but also to the fact
that physical exercise on a regular basis affects neurotransmitters which
regulate central thermoregulation.
PMID- 9651904
TI - Influence of bilateral oophorectomy upon lipid metabolism.
AB - OBJECTIVES: Reduction in serum level of estrogen has been thought to result in
hyperlipidemia which triggers atherosclerosis, and even to lead to cardiovascular
diseases, in postmenopausal women. The present study was designed to investigate
the influence of bilateral oophorectomy (OPX), which induces as much reduction in
serum estrogen level as menopause, upon lipid metabolism, especially the serum
levels of total cholesterol. METHODS: In 31 OPX subjects and 31 age- and body
size-matched premenopausal controls, the serum levels of total cholesterol (TC),
triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density
lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C),
apoprotein-A1 (Apo-A1), apoprotein-B (Apo-B), lipoprotein lipase (LPL) and
lipoprotein-a [LP(a)] were measured as indices of lipid metabolism and the index
of arteriosclerosis was calculated. RESULTS: TC level was significantly higher in
the OPX group than in the premenopausal control group, being 8995 +/- 244 (mean
+/- S.E.) mmol/l and 7757 +/- 228 mmol/l, respectively. LDL-C and Apo-B levels
and the index of arteriosclerosis were all significantly higher in the OPX group
than in the premenopausal control groups. However, there were no significant
intergroup differences with regard to HDL-C, Apo-A1, LPL and LP(a). CONCLUSIONS:
The above results demonstrated that, in spite of no reduction in HDL-C, the blood
levels of Apo-B, LDL-C and TC change due to OPX. These changes suggest OPX
induces cardiovascular diseases and, therefore, follow-up of the changes in lipid
metabolism is required, paying special attention to Apo-B and LDL-C.
PMID- 9651905
TI - Postmenopausal hormone replacement therapy and autoantibodies against oxidized
LDL.
AB - OBJECTIVES: Oxidative modification of low-density lipoprotein (oxLDL) has been
suggested to play an important role in the pathogenesis of atherosclerosis, and
autoantibodies against oxLDL have recently found to reflect this process. The
antioxidant effect and inhibition of LDL oxidation may be one of the
cardioprotective mechanisms of postmenopausal estrogen therapy. METHODS: The
effects of postmenopausal hormone replacement therapy (HRT) on the concentrations
of serum lipids and oxLDL autoantibodies were studied in a population-based
prospective 1-year study with 64 early postmenopausal women (mean age 52.2 +/-
0.4 (S.E.M.) years). The participants were randomized into two treatment groups:
HRT-group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone
acetate alone or in combination with vitamin D3, 300 IU/day + calcium lactate,
500 mg/day (n = 31) and the non-HRT-group: Calcium lactate, 500 mg/day alone or
in combination with vitamin D3, 300 IU/day (n = 33). The groups were well matched
regarding age, body mass index and baseline serum lipid concentrations. RESULTS:
The serum concentrations of total cholesterol and LDL-cholesterol decreased in
the HRT-group (4.1%, P = 0.05 and 6.4%, P = 0.03, respectively, paired t-test)
but did not change in the non-HRT-group. No changes in the serum concentrations
of HDL-cholesterol or triglycerides were observed. Additionally, no changes in
oxLDL autoantibody concentrations were observed in either group. CONCLUSIONS:
Although 1-year HRT lowered serum total- and LDL-cholesterol levels, it did not
influence oxLDL antibody titers. On the basis of the present results we cannot
question the possibility of there being beneficial effects of HRT on the
oxidative modification of LDL. However, this effect is not reflected in the
levels of oxLDL autoantibodies.
PMID- 9651906
TI - Effect of a HMG-CoA reductase inhibitor combined with hormone replacement therapy
on lipid metabolism in Japanese women with hypoestrogenic lipidemia: a
multicenter double-blind controlled prospective study.
AB - OBJECTIVES: Menopause is associated with a rise in serum lipid concentrations. We
compared a regimen of pravastatin alone with pravastatin and hormone therapy in
postmenopausal women with hyperlipidemia. METHODS: We performed a double-blind,
randomized, multicenter controlled study in postmenopausal women with
hyperlipidemia. The women were randomly assigned to receive pravastatin alone (M
group; n = 25) or pravastatin and hormone replacement therapy (HRT) (MC group; n
= 32) for 12 weeks. Serum lipid and estrogen concentrations were measured at
baseline and after 4 weeks and 12 weeks of treatment. RESULTS: The two groups
were similar with respect to baseline demographic characteristics such as age,
height, and body weight. As compared with baseline, the total cholesterol (TC)
concentration was 15.0% lower at 4 weeks and 17.7% lower at 12 weeks in the M
group and 15.1% lower at 4 weeks and 18.3% lower at 12 weeks in the MC group. The
low-density-lipoprotein cholesterol (LDL-C) concentration decreased by 25.0% at
both 4 weeks and 12 weeks in the M group and by 26.8% at 4 weeks and 30.0% at 12
weeks in the MC group. Serum TC and LDL-C concentrations were significantly lower
in the MC group than in the M group after 4 weeks of treatment, but there was no
significant difference between the groups in serum lipid concentrations after 12
weeks. Pravastatin combined with HRT was therefore suggested to lower serum lipid
concentrations earlier than pravastatin alone. There were no significant
differences between the treatment groups in serum high-density-lipoprotein
cholesterol concentrations or triglyceride concentrations after the initiation of
therapy. In the MC group, there was a significant positive correlation between
the percentage change in serum lipid concentrations and that in estrogen
concentrations, suggesting that the HRT-induced rise in estrone (E1) as well as
that in estradiol (E2) contributed an improved serum lipid profile. TC and E2,
and LDL-C and serum E1 had significant negative correlation at 12 weeks and 4
weeks, respectively. Pravastatin had no apparent effect on endogenous estrogen
levels and was not associated with any side effects, which confirmed that
pravastatin is safe, either alone or in combination with HRT. CONCLUSIONS: The
combination of pravastatin and HRT in the management of hyperlipidemia in
postmenopausal women is very useful therapeutically, because it additionally
provides the broad benefits of HRT, without compromising the lipid lowering
effects of either treatment.
PMID- 9651907
TI - T score of trabecular and cortical bone in normal postmenopausal women.
AB - OBJECTIVE: The T score of the cortical and trabecular bone compartments (T score
of BMDTrab and T score of BMDCorti) was calculated in healthy postmenopausal
women to determine which bone compartment loses more bone mass. MATERIAL AND
METHODS: A total 134 healthy postmenopausal women (mean age 55.1 +/- 6.4 years)
and 67 healthy premenopausal women (mean age 36.0 +/- 8.6 years) were studied.
Determinations were made using peripheral quantitative computed tomography (pQCT)
of the nondominant forearm. The postmenopausal women were divided into groups by
years since menopause (YSM): two early postmenopausal groups: < 5 YSM and 6-10
YSM; and two late postmenopausal groups: 11-20 YSM and > 20 YSM. RESULTS: There
was a significant correlation between the T score of BMDTrab and the T score of
BMDCorti (P < 0.0001). Both correlated negatively and significantly with age (P <
0.001 and P < 0.0001, respectively) and neither correlated with weight. The
Wilcoxon test showed no significant differences between the trabecular and
cortical T scores in the overall group of women. By YSM, only the > 20 YSM group
showed significant differences (P < 0.005). The ANOVA post hoc Bonferroni/Dunn
test showed a significant difference in the T score of BMDTrab by YSM only in the
< 5 YSM versus 11-20 YSM groups (P = 0.007) and in the < 5 YSM versus > 20 YSM
groups (P < 0.0001). The T score of BMDCorti by YSM differed significantly only
between the < 5 YSM versus 11-20 YSM groups (P < 0.0001) and between the 11-20
YSM and > 20 YSM groups (P < 0.005). CONCLUSION: In contrast with what has been
postulated in recent studies, our results showed that postmenopausal bone loss
was similar in the cortical and trabecular bone compartments in the first 20
years after menopause. Trabecular bone loss was greater than cortical bone loss
in late menopause (> 20 years).
PMID- 9651908
TI - Are menopausal symptoms associated with bone mineral density and changes in bone
mineral density in premenopausal women?
AB - BACKGROUND: The relationship between menopausal symptoms and bone mineral density
(BMD) was examined in 290 premenopausal women, ages 44-50 years, participating in
a randomized clinical trial of a dietary and exercise intervention: The Women's
Healthy Lifestyle Project. METHODS: Information on hot flashes (presence,
absence), menstrual cycles (irregular, regular) and menstrual flow per period
(variable, same) over the past 6 months was collected at entry. Participants
reporting at least one menopausal symptom were classified as symptomatic and
compared to those having no symptoms. Bone mineral density (BMD) at the lumbar
spine (L1-L4), total hip and whole-body were made at baseline and at 30 months
using a dual-energy X-ray absorptiometer (Hologic QDR 2000 densitometer).
RESULTS: Baseline BMD at the spine, hip and whole-body were significantly reduced
in women reporting menopausal symptoms compared to asymptomatic women, after
adjustment for age, weight and intervention status (all p < 0.05). Women with
irregular menstrual cycles had greater annualized rates of bone loss at the spine
and hip than asymptomatic women (spine, -0.77 (1.6)% per year vs. -0.19 (1.0)%
per year, p = 0.0043; hip, -0.37 (1.1)% per year vs. -0.04 (1.0)% per year, p =
0.061), after adjustments for age, percent change in weight, intervention status,
and baseline BMD. Similar findings were not found for whole-body BMD.
CONCLUSIONS: These results suggest that menopausal symptoms are useful for the
effective identification of premenopausal women at higher risk of low BMD and
perhaps, of osteoporosis.
PMID- 9651909
TI - Comparison of the transdermal delivery of estradiol from two gel formulations.
AB - OBJECTIVE: Conventional oral oestrogen replacement therapy can relieve
postmenopausal symptoms but is associated with undesirable side-effects which can
be minimised by avoiding the fluctuating hormonal blood levels resulting from
oral therapy and eliminating hepatic first-pass metabolism by the use of the
transdermal route. The two commercially available transdermal gel formulations
differ in composition and application recommendations. Sandrena Gel contains 0.1%
(w/w) and Oestrogel 0.06% (w/w) estradiol and recommended dosages are 0.5-1.5 g
over 200-400 cm2 (Sandrena Gel) and 2.5 g gel over 720 cm2 (Oestrogel). In
transdermal therapy the formulation composition may have a significant effect on
drug delivery and we have therefore compared the permeation of estradiol from
these formulations across human skin in vitro. METHODS: The in vitro percutaneous
penetration of estradiol from the formulations through epidermal membranes
prepared from excised female human thing skin was assessed over a 24 h period
using static type Franz diffusion cells. RESULTS: Permeation of the active was
similar from each formulation representing (at 24 h) 18.2 +/- 3.5% of the applied
dose from Sandrena Gel and 17.4 +/- 4.8% of the applied dose from Oestrogel.
These percentages equate to cumulative skin permeations of 0.65 +/- 0.15
microgram/cm2 and 0.45 +/- 0.15 microgram/cm2 respectively. CONCLUSION: The
results suggest that the two formulations are bioequivalent at the recommended
dose levels.
PMID- 9651910
TI - Image-guided neurosurgery comparing a pointer device system with a navigating
microscope: a retrospective analysis of 208 cases.
AB - A retrospective analysis of neuronavigation procedures performed at the Vienna
Neurosurgical Clinic was undertaken to elucidate the advantages of 2 technically
different navigation systems in clinical use. In a 30-month period, 208 frameless
stereotactic procedures were performed using a stereotactic microscope (MKM
System, Zeiss; 92 procedures in 87 patients; 47 female, 40 male; mean age, 46
yrs) and a light emitting diode (LED) based pointer navigation device (Easy Guide
Neuro (EGN), Philips; 116 procedures in 114 patients; 63 female, 51 male; mean
age 46.4 yrs). The navigating microscope was exclusively used for cranial
navigation, the pointer device system in 107 cases for cranial and in 9 cases for
spinal navigation. Procedures were CCT-guided in 109 cases, MRI-guided in 95, and
both CT/MRI guided in 4 cases. Skin fiducials were used in all these procedures.
The MKM system provided coordinate-based navigation, similar to frame systems.
This allowed surgical planning and performance using stereotactic coordinates for
target calculation. Additionally, tumor volumes were defined by contours and
projected into the ocular of the microscope, allowing guidance during targeting
and resection of lesions. Both of these features proved beneficial in tumor
surgery (60.8% MKM cases), cavernoma surgery (21.8% MKM cases), and epilepsy
surgery (14.1% MKM cases). In contrast to the microscope, the pointer navigation
system could be employed for intuitive correlation of image points with points of
interest in the operating field by using a LED-equipped pointer device. This
permitted image guidance during a wide spectrum of neurosurgical procedures, in
tumor surgery (68.1% EGN cases), cavernoma surgery (5.1% EGN cases), epilepsy
surgery (14.1% EGN cases), vascular surgery (3.4% EGN cases), spinal surgery
(7.8% EGN cases), and guidance for burr holes and drainages (6.9% EGN cases),
without calculating stereotactic coordinates. This analysis showed clear
differences in the application of the two systems and may facilitate the decision
as to which system best meets the individual demands of a neurosurgical
department.
PMID- 9651911
TI - MiniMATCH: a simple method for local data transfer between MRI and CT scan sets.
AB - A comparison of the spatial position of distinct locations within cranial MRI and
CT scan sets can easily be done with a simple algorithm designed as a computer
program. After determination of a basic system formed by the coordinates of
anatomical landmarks in CT and MRI, arbitrary points can be identified on one
scan set and transferred quantitatively to the other. Pros and cons of the method
are discussed and opposed to the properties of specifically designed image
processing systems.
PMID- 9651912
TI - Control of hemorrhage during AVM surgery--with special reference to treatment of
dilated capillaries and arteries around the nidus.
AB - Control of hemorrhage during AVM surgery is one of the key issues to prevent
NPPB. Inadequate procedures for hemostasis of feeders and drainers, so-called
dilated capillaries and arteries (moja moja blood vessels) that are located on
the side facing the normal brain, and inappropriate surgical strategies for
intraoperative hemorrhage from these blood vessels are frequently the main cause
of the difficulty in achieving hemostatic control. We conclude that it is
important to aggressively reduce the occurrence of intraoperative hemorrhage and
prevent or minimize the dilatation of abnormal capillaries and arteries due to
inappropriate surgical procedures on the basis of the fundamental surgical
strategy, i.e., feeder-->nidus-->drainer. Adequately securing the length and
adequate coagulation of hemorrhagic blood vessel, employing a skillful bipolar
coagulator technique aimed at controlling intraluminal pressure and blood flow on
the central side, are believed to be key factors in hemorrhage treatment.
PMID- 9651913
TI - Endoscopic endonasal transsphenoidal approach to the sella: towards functional
endoscopic pituitary surgery (FEPS).
AB - Standard microscopical transsphenoidal surgery is used world-wide in most sellar
lesions, but continuing technological progress leaves room for further
possibilities. The authors have employed a slightly modified Jho-Carrau technique
for endoscopic endonasal transsphenoidal removal of pituitary lesions. This
approach has been successfully used in 15 consecutive patients; the preliminary
results are reported. The advantages and the limitations of this technique are
discussed and compared to standard transsphenoidal surgery. In consideration of
the low invasiveness of this approach and of the improved respect for the inner
nose and sinus structures, the authors suggest the new term of Functional
Endoscopic Pituitary Surgery (FEPS) to characterize this simple one-nostril
endoscopic endonasal procedure.
PMID- 9651914
TI - Endoscopic neurosurgery: report of the first five cases done in Malaysia using
the Caemaert-Abdullah method.
AB - The first endoscopic procedure done in Malaysia using the Caemaert-Abdullah
method is reported and the followup results showed an excellent neurosurgical
outcome. A 16-year-old girl with an aqueduct stenosis was operated on using a
free-hand, computer-assisted endoscopic method where a third ventriculostomy was
done. This was the first case being carried out in the Hospital Universiti Sains
Malaysia. The next two cases were a suprasellar pituitary cyst in an elderly man
and a child with an obstructive hydrocephalus who was previously shunted which
became infected. Both endoscopic procedures, extirpation of the cyst using a
Nd:Yag laser and a third ventriculostomy, respectively, were done under general
anaesthesia in the supine position. Follow-up revealed a transient diabetes
insipidus in all three cases up to 48 hours after the operation which resolved
spontaneously. The fourth case involved an endoscopic removal of retained
ventricular catheter after rectal migration of a shunt in an eight-year-old girl
with congenital hydrocephalus. The fifth was a free-hand endoscopy with
perforation of multiple brain septae in a ten-month-old baby with hydrocephalus
secondary to meningitis. The final outcomes for all the cases were favourable
hence we conclude that endoscopic neurosurgery is a safe procedure and hope that
more neurosurgeons will continue to use this method, especially for the
management of intraventricular cyst and hydrocephalus and especially in South
East Asia.
PMID- 9651915
TI - A malleable endoscopic suction instrument: technical note.
AB - Flexible endoscopes are being employed for a variety of neurosurgical procedures.
These instruments have drawbacks, especially in their ability to evacuate clotted
blood. We have attempted to rethink the design of these instruments and have
developed a malleable endoscopic suction instrument. This has proved to be
helpful in a variety of intracranial and intraspinal procedures.
PMID- 9651916
TI - Intracranial aneurysms: a review of endovascular and surgical treatment in 248
patients.
AB - We reviewed the medium-term results of endovascular treatment of intracranial
aneurysms and compared patient selection and results with those of open surgery.
Between January 1992 and December 1995, a total of 248 consecutive patients were
treated for 297 aneurysms (61 unruptured and 236 ruptured). 162 aneurysms in 142
patients (mean age, 48.5 years) were treated microsurgically and 134 aneurysms in
106 patients (mean age, 54.2 years) were treated by endovascular embolization
with Guglielmi detachable coils (GDC). The mean follow-up was 2.6 years (range,
1.5 to 4.5 years). There was no significant difference in patient population and
selection in terms of age, sex or location of aneurysms between both methods.
Both modalities achieved excellent results (defined as no neurological deficit)
in patients with unruptured aneurysms and with no or minor deficits after
subarachnoid hemorrhage (SAH) between 71% and 88%. Patients with moderate
deficits after SAH had excellent outcomes in 49% after open surgery, and 47%
after embolization. Poor grade patients had, equally, as well an acceptable as a
pour outcome, between 0% and 50%. There was no significant difference between the
outcome of surgical or endovascular patients. We conclude that GDC embolization
is not associated with a higher risk of morbidity and mortality than open
surgery. This risk may even be lower for lesions in surgically unfavorable
locations. The GDC technique is a less invasive, effective option to prevent re
bleeding in early stage, even in poor-grade patients. However, these encouraging
medium-term results have to be confirmed by a longer observation period.
PMID- 9651917
TI - Conservative management of acoustic neurinomas: prospective study of long-term
changes in tumor volume and auditory function.
AB - Recently reported retrospective analysis on the natural courses of acoustic
neurinomas have disclosed that 26-86% of tumors show very slow, or no, growth for
many years. To our knowledge, however, there have been no prospective analyses of
the natural course of these tumors. We prospectively analyzed tumor growth as
well as auditory function changes in 12 patients (13 tumors) managed
conservatively. All 12 patients were advised to undergo both pure tone audiometry
and magnetic resonance imaging at 3-4 month intervals for the first follow-up
year and at 1-2 year intervals thereafter. Then, in the event of either
significant tumor growth (> 20% volume increase) or hearing deterioration (> 10
dB), a decision would be made as to whether the patient should undergo either
surgery or radiosurgery. A significant increase in tumor volume was confirmed in
seven of the 13 tumors during the mean observation period of 564 days (88-1269
days). In another patient, though neither tumor growth nor worsening of auditory
acuity was significant, the patient complained of subjective change in the
symptoms. Therefore, we decided to treat eight (62%) of the 13 tumors. In
contrast, neither tumor growth nor worsening of auditory acuity has as yet
occurred in the remaining five tumors (38%) which have been observed for a mean
period of 627 days (342-1377 days). Careful follow-up of these five patients is
ongoing. Although further long-term follow-up is clearly necessary, conservative
treatment appears to be a reasonable alternative to immediate treatment for
selected patients with acoustic neurinomas.
PMID- 9651918
TI - Coronally oriented vertical fracture of the axis body: surgical treatment of a
rare condition.
AB - The neurosurgical management in a rare case of vertical axis fracture is
presented along with discussion of the supposed pathogenetic mechanisms and the
biomechanics underlying this type of cervical spine injury. Comprehensive
neuroradiological investigation prior to surgery clearly demonstrated the
dislocation of the anterior part of the axis body with concomitant C 2/C 3-disk
injury. Therefore, the unstable fracture had to be managed by a one-time combined
ventrodorsal approach using anterior C 2-C 3 locking plate fusion and C 2
bilateral dorsal transpedicular screw fixation. No operative morbidity resulted
from this procedure, and stable bony fusion was achieved with minimal restriction
of head mobility and with minor residual complaints. This case illustrates the
variable biomechanical response of the upper cervical spine to trauma and the
advantages of a non-standard surgical approach for internal fixation of the
injured cervical spine.
PMID- 9651919
TI - Foot drop following brain tumors: case reports.
AB - Three cases with foot drop following brain tumors in patients suffering from
parasagittal pathology are reported. Foot drop was the first complaint in the
patients in our series. We generally notice foot drop as a sign of lumbar disc
herniation or peroneal nerve lesions but rarely foot drop may also occur with
brain lesions.
PMID- 9651920
TI - Mirror movements associated with cervical meningocele: case report.
AB - A patient with mirror movements associated with cervical meningocele has been
presented in this report. The MRI showed normal cerebrum and cervical
meningocele, and an anomaly at the posterior to the cervical spinal cord-medulla
junction. Unilateral transcranial magnetic stimulation evoked bilateral responses
at similar latencies on the thenar muscles which are quite different from those
observed in normal subjects. This case adds another etiological cause to the
mirror movements.
PMID- 9651921
TI - The relative contribution of antibody production and CD8+ T cell function to
immune control of Trypanosoma cruzi.
AB - The life cycle of the protozoan parasite Trypanosoma cruzi in mammalian hosts
includes both non-dividing trypomastigote forms which circulate in the blood and
replicating intracellular amastigotes which reside within the cytoplasm of a
variety of host cells. In this study we have used mice with induced mutations in
genes responsible for either antibody production or cytolytic T lymphocyte (CTL)
function to examine the relative contributions of these effector mechanisms to
control of T. cruzi. Mice deficient in the production of antibodies exhibited a
delay in the rise in acute phase parasitaemia and an extended time to death
relative to mice lacking CD8+ T cells. Nevertheless, B cell deficient mice
eventually succumbed to the infection. Prior infection with an avirulent strain
of T. cruzi failed to protect either CD8+ T cell-deficient mice or B cell
deficient mice from challenge infection with virulent parasites. In contrast,
mice with disruptions in the genes controlling perforin- or granzyme B-mediated
cytolytic pathways had parasitaemia and mortality rates similar to wild-type mice
and were protected from secondary infection by prior exposure to avirulent
parasites. These results 1) confirm that antibody production, although secondary
in importance to cellular responses, is nevertheless absolutely required and 2)
perforin- or granzyme B-mediated lytic pathways are not required for control of
T. cruzi infection.
PMID- 9651922
TI - The immune response and immunopathology in infection with Schistosoma mansoni: a
key role of major egg antigen Sm-p40.
AB - The immune response and related granulomatous inflammation in infection with
Schistosoma mansoni are ultimately dependent on SEA-sensitized CD4+ Th cells and
comprise multiple pathways variously involving the activation and recruitment of
different cell populations and the production of different inflammatory
cytokines, all under the influence of regulatory genetic factors. The spontaneous
downregulation of granuloma formation (immunomodulation), in turn, is a well
known phenomenon, but the full extent of its precipitating factors is still
uncertain. This review describes a pathway leading to immunomodulation that
features at its centre the down-regulatory cytokine IL-10. This mechanism is
attractive because it offers a cogent correlation between findings in the
laboratory and those displayed by patients affected with the disease. The Sm-p40
antigen, a major component of schistosome eggs, elicits a strong CD4+ Th cell
response in H-2k mice that correlates with intense granuloma formation; in
contrast, its immunogenicity is relatively minor during infection of other mouse
strains that develop smaller granulomas. Of great interest is that the Sm-p40
antigen only elicits a Th-1 type cytokine response, a phenotype that remains
constant even as the overall response to SEA shifts to a Th-2 type. The Sm-p40
molecule has a dominant epitope that is the target of CD4+ Th cells from infected
H-2k mice; indeed, a minimal peptide that bears the epitope binds to I-Ak. The
importance of pursuing a systematic elucidation of the major egg antigens,
resides in the exciting possibility of specifically desensitizing the CD4+ Th
cells that mediate granuloma formation, which may achieve meaningful prevention
or amelioration of clinical disease.
PMID- 9651923
TI - Setting in motion the immune mechanisms underlying genetically determined
resistance and susceptibility to infection with Leishmania major.
AB - The murine model of infection with Leishmania major has allowed the demonstration
of a causal relationship between, on the one hand, genetically determined
resistance to infection and the development of a Th1 CD4+ cell response, and on
the other hand, genetically determined susceptibility and Th2 cell maturation.
Using this murine model of infection, the role of cytokines in directing the
functional differentiation pathway of CD4+ T cell precursors, has been
demonstrated in vivo. Thus, IL-12 and IFN-gamma have been shown to favour Th1
cell development and IL-4 is crucial for the differentiation of Th2 responses.
Maturation of a Th2 response in susceptible BALB/c mice following infection with
L. major is triggered by the IL-4 produced during the first two days after
parasite inoculation. This IL-4 rapidly renders parasite specific CD4+ T cells
precursors unresponsive to IL-12. A restricted population of CD4+ T cells
expressing the V beta 4V alpha 8 TCR heterodimer and recognizing a single epitope
on the LACK (Leishmania Activated C-Kinase) antigen of L. major is responsible
for this rapid production of IL-4, instructing subsequent differentiation towards
the Th2 phenotype of CD4+ T cells specific for several parasite antigens.
PMID- 9651924
TI - A protective role for IL-6 during early infection with Toxoplasma gondii.
AB - IL-6 deficient mice were found to be significantly more susceptible to peroral
infection with Toxoplasma gondii than their wild-type counterparts as measured by
survival, brain cyst burdens and brain pathology at 28 days post infection. The
physical manifestations of disease, such as weight loss, were not observed in IL
6 deficient animals until at least seven days later than such changes occurred in
wildtype mice. During this early stage of infection IL-6+/+ but not IL-6-/- mice
mounted a peripheral blood neutrophilia. Furthermore, between 6-8 days post
infection there was a significant increase in plasma IFN-gamma levels in wild
type but not IL-6 deficient mice. Not until days 18-23 post-infection, concurrent
with the majority of deaths in IL-6-/- mice, were plasma IFN-gamma levels
substantially and significantly raised in IL-6-/- mice. At this time not only
were these plasma IFN-gamma levels 20-fold higher than background but eight-fold
greater than peak (6-8 days post-infection) IFN-gamma levels in IL-6+/+ mice. IFN
gamma dependent parasite specific IgG2a levels were also significantly higher in
IL-6-/- mice over this period and thereafter. Overall the evidence suggests that
in the absence of IL-6 mice are unable to initiate a rapid proinflammatory
response against T. gondii, which allows increased parasite growth. Increased
mortality in IL-6-/- mice may be directly due to this increased parasite burden
and the excessive inflammatory response this induces three weeks post-infection.
PMID- 9651925
TI - Profound suppression of cellular proliferation mediated by the secretions of
nematodes.
AB - Loss of T lymphocyte proliferation and the emergence of a host response that is
dominated by a Th2-type profile are well-established features of human filarial
infection. Down-regulation and modulation of host T cell responses during
lymphatic filariasis has been investigated by implantation of parasite stages
into inbred mice. Adherent peritoneal exudate cells (PEC) from mice transplanted
with adult or larval Brugia malayi parasites are profoundly anti-proliferative
but do not prevent antigen-specific cytokine production by T cells. We
demonstrate here that the excretory/secretory (E/S) products of the adult
parasite are sufficient to induce PEC that block proliferation if injected daily
into mice. We have previously shown that in vivo production of host IL-4 is
required for the generation of suppressive cells. Because the induction of host
IL-4 is characteristic of infection with nematodes, we asked whether E/S from two
other nematode parasites, Nippostrongylus braziliensis and Toxocara canis were
also capable of generating a suppressor cell population. Injection of E/S from
these two parasites also led to a reduction in T cell proliferation suggesting
that this mechanism of down-regulating host responses is a feature common to
nematode parasites.
PMID- 9651926
TI - The effect of nematode infection upon intestinal smooth muscle function.
AB - Nematode infections are useful in studying both host defence and inflammation
induced changes in intestinal physiology, including increased contraction by
intestinal muscle. Our initial studies of the heightened muscle function found
during T. spiralis infection led to investigations of the role of immune and
inflammatory cells and mediators in the immunodulation of intestinal muscle
function. By infecting various immunodeficient mouse strains, as well as gene
transfer to the intestine, T lymphocytes, and in particular the CD4+ve subset
were found to be responsible for altering smooth muscle function. However,
eosinophils as well as the cytokine interleukin-4 may also be involved.
Investigations also indicate a potential role for increased muscle function and
propulsive activity in expelling nematode parasites. Mutant mice which suffer
aberrant intestinal propulsion, or based upon an immunodeficiency, undergo
reduced changes in muscle function during infection, undergo prolonged
infections. While increased muscle function may be an adaptive host response, the
changes in muscle function may persist long after the resolution of the
infection. Thus understanding the mechanisms behind the immunomodulation of
intestinal muscle function may also impact upon clinical gastroenterology, since
motility disturbances in man often occur following enteric infections, or other
inflammatory conditions of the bowel.
PMID- 9651927
TI - Role of neutrophils in innate resistance to Entamoeba histolytica liver infection
in mice.
AB - In order to define the role of neutrophils in the innate resistance to Entamoeba
histolytica liver infection in mice, we examined the pattern of liver lesion
induced by direct injection of E. histolytica trophzoites in normal mice and in
neutrophil-depleted mice. A variety of histological lesions were found, the
extent of liver damage was considerably higher in the neutrophil-depleted mice.
Livers from neutrophil-depleted mice displayed areas of liquefactive (lytic)
necrosis containing a large number of amoebae and absence of neutrophils or
mononuclear cells. By contrast, in the liver of normal mice, neutrophils were
seen associated to E. histolytica at early stages of infection. In both mouse
groups, areas of TUNEL-positive dead hepatocytes were observed and a
characteristic internucleosomal banding pattern of genomic DNA consistent with
apoptosis was detected in DNA harvested from amoebic liver lesions. These data
suggest that neutrophils play an important role in the mechanisms of resistance
to amoebic liver infection in mice. In addition, our histological analysis
suggests that E. histolytica is capable of producing liver damage in the absence
of inflammatory cells.
PMID- 9651929
TI - Intestinal mast cell response and mucosal defence against Strongyloides
venezuelensis in interleukin-3-hyporesponsive mice.
AB - Recently several inbred strains of mice were found to be hyporesponsive to
Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that
encodes IL-3 receptor alpha subunit (IL-3R alpha). Due to this mutation, mast
cells were not generated in vitro from bone marrow cells of these mice under the
presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation
is dependent on IL-3, are important effector cells in immune-mediated expulsion
of intestinal nematodes, Stronglyoides spp. In the present study, therefore, we
examined intestinal mast cell response and mucosal defence against Strongyloides
venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous
inoculation with 10,000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice
showed identical kinetic patterns of daily faecal egg output and intestinal mast
cell response. When these mice were infected with 3000 L3 and, five weeks later,
they were challenged by intraduodenal implantation of 800 S. venezuelensis adult
worms, the timing of logarithmic decline of faecal egg count as well as
intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of
intestinal mastocytosis and faecal egg excretion after a primary and challenge
infection in A/J mice, another IL-3-hyporesponsive strain, were identical with
those seen in C58/J mice. These results suggest that intestinal mast cell
response and mucosal defence against S. venezuelensis of the mutant mice were
almost completely compensated in vivo. Possible mechanisms of induction of
intestinal mast cell response in IL-3R alpha-defective mice are discussed.
PMID- 9651928
TI - Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of
Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in
immunity to malaria.
AB - MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism
of protection is not clear. To determine whether MSP1(19)-specific effector T
cells can control parasitaemia, we analysed the specificity of T cells induced
following immunization with recombinant forms of P. yoelii MSP1(19) and asked
whether they could protect mice. There was no evidence that effector T cells were
capable of protecting since: (1) immunization of mice with yMSP1(19), but not
defined epitopes, was able to induce protection; and (2) long term MSP1(19)
specific CD4+ T cell lines were incapable of adoptively transferring protection.
In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic
antibody response to MSP1(19) after either challenge with MSP1(19) or parasite.
Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the
targets of helper T cells for antibody response but not of identified effector T
cells capable of controlling parasitaemia.
PMID- 9651930
TI - Protection of Fasciola hepatica in the gut mucosa of immune rats is associated
with infiltrates of eosinophils, IgG1 and IgG2a antibodies around the parasites.
AB - We investigated the immune effector mechanisms that underlie protection against
F. hepatica in the gut wall of immune rats, using (immuno)histochemistry. In the
lamina propria of immune Wistar rats, four weeks after oral infection,
frequencies of IgE-positive cells, eosinophils and mucosal mast cells were
significantly increased, compared with naive rats. These factors represent the
traditional effector mechanisms against helminths. No significant differences
were detected between the two groups in frequencies of IgM-, IgG2a-, IgG1- and
IgA- positive cells, CD4- and CD8-positive cells, NK cells, macrophages,
neutrophils or goblet cells. Upon challenge of immune rats with F. hepatica in an
ex vivo gut segment, NEJs that migrated through the (sub)mucosa were coated with
IgG1 and IgG2a antibodies and surrounded by eosinophils. No IgE or IgA antibodies
were detected on the parasites. The onset of these immune effector responses, two
h after challenge, was related to the expression of protection. These results
suggest that NEJs are killed by an eosinophil-mediated cytotoxic response
involving IgG antibodies. These antibodies were not produced in the intestine,
but infiltrated the gut upon challenge. The observed immune effector responses
were not restricted to the site where the primary infection is located, namely
the small intestine, but were also detected in the large intestine. The presence
of the protective immune mechanisms in two other rat strains demonstrates the
pivotal importance of these responses, irrespective the genetic background of the
host.
PMID- 9651931
TI - Immunoregulation in experimental murine Trypanosoma congolense infection: anti-IL
10 antibodies reverse trypanosome-mediated suppression of lymphocyte
proliferation in vitro and moderately prolong the lifespan of genetically
susceptible BALB/c mice.
AB - We infected highly susceptible BALB/c and relatively resistant C57BL/6 mice with
cloned Trypanosoma congolense and followed the effects of these infections on the
circulating parasite numbers, mouse mortality and cytokine expression. C57BL/6
mice controlled their parasitaemia and survived for up to 163 +/- 12 days, while
BALB/c mice could not control their parasitaemia and succumbed to the infection
within 8.4 +/- 0.5 days. Susceptible BALB/c mice had dramatically higher plasma
levels of IL-10 than the resistant C57BL/6 mice from day 7 forward. This was
preceded by an earlier and higher level induction of splenic IL-10 messenger RNA
(mRNA) expression in the infected BALB/c mice. There was a strong negative
correlation between the splenocyte proliferative responses to Concanavalin-A (Con
A) and their production of IL-10 in these infected BALB/c mice. Co-treatment of
the Con-A-stimulated spleen cell cultures with monoclonal anti-IL-10 antibodies,
but not isotype-matched control antibodies, could completely reverse this
suppression of the splenocyte proliferative response. Finally, in three
experiments, anti-IL-10 antibody treatment in vivo reduced the peak circulating
parasitaemia of infected BALB/c mice by 43% and increased their median survival
periods by 38% relative to isotype-matched control antibody-treated mice.
PMID- 9651932
TI - Seasonal changes in the Plasmodium falciparum population in individuals and their
relationship to clinical malaria: a longitudinal study in a Sudanese village.
AB - Residents of Daraweesh village in Sudan were monitored for Plasmodium falciparum
infection and malaria morbidity in 3 malaria seasons from 1993 to 1996. Malaria
parasites were detected microscopically and by polymerase chain reaction (PCR) in
a series of cross-sectional surveys. PCR revealed submicroscopical infections
during the dry season, particularly among individuals who had recovered from a
malaria episode following successful drug treatment. Clinical and subclinical
infections were contrasted by assaying for allelic polymorphism at 2 gene loci,
MSP-1 and GLURP and 2 hypotheses examined with reference to these data: that
clinical malaria is associated with infection with novel parasite genotypes not
previously detected in that host, or alternatively, that clinical malaria
episodes are associated with an increased number of clones in an infection. We
detected more mixed infections among clinical isolates, but people carrying
parasites during the dry season were not found to have an increased risk of
disease in the following malaria season. There was a clear association of disease
with the appearance of novel parasite genotypes.
PMID- 9651933
TI - Formation of basement membrane-like structure terminates the cellular
encapsulation of microfilariae in the haemocoel of Anopheles quadrimaculatus.
AB - The encapsulation of microfilariae in the haemocoels of mosquitoes combines both
humoral and cellular reactions: the microfilariae are first encased in an
acellular layer of melanin, followed by a cellular encapsulation by
plasmatocytes. In this study, we demonstrated that cellular encapsulation of
Brugia pahangi microfilariae in the haemocoel of the mosquito Anopheles
quadrimaculatus was terminated by the formation of a basement membrane-like
structure on the outermost surface of the cellular capsule. This structure
occurred in the early stage of cellular encapsulation and was evident on the
exterior surface of the plasmatocyte, when the active haemocytes were attaching
to the already melanized microfilariae. The termination structure appears to be
laid down by releasing the vesicle inclusions of haemocytes and has similarities
in ultrastructure and cationic colloidal gold staining properties with that of
mosquito basement membranes.
PMID- 9651934
TI - Effect of praziquantel treatment on experimental porcine Schistosoma japonicum
infection.
AB - The aims of the study were to assess the effect of praziquantel on Schistosoma
japonicum infection in pigs, and to elucidate the level of resistance to
reinfection after treatment. Pigs were given a single infection with S. japonicum
followed by a praziquantel treatment (40 mg/kg) week 8, reinfection week 12 and
perfusion week 20 post-primary infection. Relevant control groups were included.
Worm burdens, faecal and tissue egg counts, gross- and histopathology of the
liver and specific liver enzymes were assessed. The results showed a 100% cure
rate of praziquantel against S. japonicum in pigs. Worm nodules were present in
equal numbers in the intestinal wall 4 and 14 weeks post-treatment. Treatment did
not significantly reduce the number of tissue eggs neither 4 nor 14 weeks post
treatment. No worm nodules or worm-induced lesions were found in the livers of
the treated pigs and the levels of liver enzymes were comparable in treated and
nontreated infected pigs. Periportal and septal fibrosis regressed following
treatment. Faecal egg counts were significantly reduced 2 (56%) and 4 (82%) weeks
after treatment. Challenge infection 4 weeks post-treatment did not result in
establishment of new worm pairs. Praziquantel proved to be highly effective
against S. japonicum in pigs without causing pathological side-effects in the
liver.
PMID- 9651935
TI - Isolation of an aspartic proteinase precursor from the egg of a hard tick,
Boophilus microplus.
AB - An aspartic proteinase precursor, herein named BYC (Boophilus Yolk pro-Cathepsin)
was isolated from eggs of the hard tick, Boophilus microplus. As judged by
electrophoresis on sodium dodecyl sulfate polyacrylamide slab gel (SDS-PAGE),
purified BYC presented 2 bands of 54 and 49 kDa, bearing the same NH2-terminal
amino acid sequence. By Western blot analysis, BYC was also found in the
haemolymph, indicating an extraovarian site of synthesis. Several organs were
incubated in culture medium with [35S]methionine, and only the gut and fat body
showed synthesis of BYC polypeptides. Protein sequencing of both the NH2-terminal
and an internal sequence obtained after cyanogen bromide (CNBr) cleavage of BYC
revealed homology with several aspartic proteinase precursors. Incubation at pH
3.5 resulted in autoproteolysis of BYC, which produced the mature form of the
enzyme, that displayed pepstatin-sensitive hydrolytic activity against
haemoglobin. Western blot analysis using anti-BYC monoclonal antibodies showed
proteolytic processing of BYC during embryogenesis and suggested activation of
the enzyme during development. A role of BYC in degradation of vitellin, the
major yolk protein of tick eggs, is discussed.
PMID- 9651936
TI - Tick salivary gland extracts promote virus growth in vitro.
AB - Saliva of blood-feeding arthropods promotes infection by the vector-borne
pathogens they transmit. To investigate this phenomenon in vitro, cultures of
mouse L cells were treated with a salivary gland extract (SGE) prepared from
feeding ticks and then infected with vesicular stomatitis virus (VSV). At low
input doses of VSV, viral yield was increased 100-fold to 10,000-fold by 16-23 h
post-infection compared with untreated cultures, and depending on the SGE
concentration. SGE-mediated acceleration of viral yield corresponded with the
earlier appearance of VSV nucleocapsid protein as detected by 2-dimensional
electrophoresis of infected cells. The observation that physiological doses of
virus (i.e. doses likely to be inoculated by an infected arthropod vector into
its vertebrate host during blood-feeding) respond to SGE treatment in vitro
provides a new opportunity for identifying the factors in tick saliva that
promote virus transmission in vivo.
PMID- 9651937
TI - Vector competence of 7 rhipicephalid tick stocks in transmitting 2 Theileria
parva parasite stocks from Kenya and Zimbabwe.
AB - The competence of 7 different stocks of Rhipicephalus appendiculatus and R.
zambeziensis to transmit 2 different stocks of Theileria parva was compared by
feeding nymphae of each tick stock simultaneously on infected cattle and
assessing the infections in the salivary glands of the resultant adult ticks.
There were significant differences in the patterns of infection of the 2 stocks
(T. parva Muguga and T. parva Boleni) in the different stocks of ticks, and these
differences were shown to be reproducible. The Muguga tick stock from Kenya and
the Zambia tick stock from Eastern Province had the highest infections of T.
parva Muguga and T. parva Boleni respectively. The Zambia Southern Province tick
stock and the Zimbabwe Mashonaland West tick stock had the lowest infections of
T. parva Muguga and T. parva Boleni respectively. The difference in mean
abundance of infection between the most and least efficient vector for T. parva
Muguga was 63.3 while that for T. parva Boleni was 54.4 infected acini. The
implications of these results for laboratory transmission of T. parva and for the
epidemiology of theileriosis are discussed.
PMID- 9651938
TI - Characterization of trypanosome infections by polymerase chain reaction (PCR)
amplification in wild tsetse flies in Cameroon.
AB - The polymerase chain reaction (PCR) method was used to characterize trypanosome
infections in tsetse flies from 3 sleeping sickness foci in Cameroon. The
predominant tsetse species found was Glossina palpalis palpalis. An average
infection rate of 12.1% was revealed by microscopical examination of 888 non
teneral tsets flies. PCR amplification analyses for trypanosome identification
were carried out on 467 flies, with primer sets specific for Trypanosoma
(Trypanozoon) brucei s.1., T. (Duttonella) vivax, T. (Nannomonas) simiae and
forest type T. (Nannomonas) congolense. Of 467 flies 93 were positive by
microscopical analysis while PCR succeeded in identifying 89 positive flies. Of
the PCR-positive flies 34 (38.2%) were negative by microscopical examination. PCR
amplification, when compared to the parasitological technique, gave a higher
estimate of infection rate of trypanosomes in natural tsetse populations. The PCR
technique did, however, fail to identify 40.9% (38/93) of the parasitologically
positive flies. The reasons for this failure are discussed. The overall
prevalence of mixed infections, assessed by PCR, was 37.1%; the majority (72.7%)
involved T. brucei and forest type T. congolense.
PMID- 9651939
TI - Observations on the mechanism of eggshell formation in the liver fluke, Fasciola
hepatica.
AB - A mechanism for eggshell production in Schistosoma mansoni has been proposed
(Wells & Cordingley, 1991), and suggests that the release of eggshell protein
globules from the vitelline cells occurs under alkaline conditions within the
ootype followed by their subsequent fusion to form the eggshell. Fusion and
tanning of these components produces eggshell which autofluoresces. The present
study was carried out to determine whether a similar process operates in Fasciola
hepatica. A number of drug treatments were used to disrupt key steps in the
maturation of vitelline cells. Treatment with the calcium ionophore lasalocid (1
x 10(-5) M) led to the premature release of eggshell globules from the vitelline
cells but not their fusion. Incubation in monensin (1 x 10(-6)M), a sodium
ionophore and ammonium chloride (NH4Cl) (5 x 10(-2) M), a weak base, resulted in
the premature fusion of eggshell protein globules within the vitelline cells and
premature tanning of the eggshell protein material. The copper-containing enzyme,
phenol oxidase, is thought to be involved in the tanning process during the
production of eggs. Diethyldithiocarbamate, (DDC, 1 x 10(-3) M) is a phenol
oxidase inhibitor and treatment with this compound, in combination treatments
with monensin and NH4Cl, prevented fusion of the vitelline cell globules and
tanning of the shell protein material. The results of the study suggest that the
mechanism for eggshell formation in F. hepatica is similar to that proposed for
S. mansoni and may be common to other trematodes as well.
PMID- 9651940
TI - Changes in the zymogenic cell populations of the abomasa of sheep infected with
Haemonchus contortus.
AB - The effects of dietary urea supplementation and of a 10-week trickle infection
regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic
population of the abomasa of Hampshire Down lambs was examined. At necropsy a
variety of parameters including plasma pepsinogen concentration, the wet weights
of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in
them, were assessed. Tissue pepsinogen concentration was measured as the total,
acid-stable proteolytic activity present in mucosal homogenates, as well as
immunohistochemically. The immunohistochemical findings were quantified using
computer-aided image analysis. Elevation of plasma pepsinogen concentrations in
infected animals was of borderline significance (P = 0.06). The fundic mucosae of
infected animals were heavier (P < 0.02) than those of control animals, but there
was no overall change in the pepsinogen content of tissues. Immunohistochemistry
revealed that infected animals had increased numbers of zymogenic cells, due to
mucous cell hyperplasia and the adaptation of cells to produce both mucins and
pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen
in uninfected animals, was reduced in infected lambs. Image analysis confirmed
that at a mid-point of the mucosa of infected animals there was increased
pepsinogen-specific immunoreactivity that corresponded with areas of mucosal
hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of
pepsinogen secretion in infected animals even if chief cell output is reduced.
PMID- 9651941
TI - The relationship between numbers of larvae recovered from the brain of Toxocara
canis-infected mice and social behaviour and anxiety in the host.
AB - The effect of the nematode Toxocara canis on social behaviour and anxiety levels
of adult male outbred (LACA) mice was examined following infection with a single
dose of 2000 ova. The actual number of larvae recovered from the brain of each
individual mouse was determined after behavioural testing. The effect of the
parasite on mouse behaviour was analysed by both the initial dose administered
(i.e. infected versus control) and the degree of infection in the brain. There
was substantial variation in the number of larvae recovered from the brains of
the individual mice and the magnitude of behavioural change was associated with
the level of infection. Examination of social behaviour for both analyses
revealed that the infection reduced levels of aggressive behaviour and increased
levels of flight and defensive behaviours. High infection in the brain induced
the greatest degree of behavioural change which decreased in mice with lower
infections. In contrast the analysis of anxiety levels in mice by initial dose
administered revealed no difference between infected and control mice. Mice with
low infection in the brain, however, displayed a greater level of risk behaviour
by spending more time in the vicinity of a predator odour and in the light area
of a light/dark paradigm than control or high infection mice. The results suggest
that the behaviour of mice infected with T. canis is influenced by the number of
larvae accumulated in the brain. This may have important consequences for the
conclusions drawn on the effect of this parasite on murine behaviour.
PMID- 9651942
TI - In memory of Professor Olav Hilmar Iversen.
PMID- 9651943
TI - Altered topographic expression of p21WAF1/CIP1/SDI1, bcl2 and p53 during gastric
carcinogenesis.
AB - The accumulation of wild-type p53 protein results in two pathways, cell cycle G1
arrest by p21WAF1/CIP1/SDI1 and apoptosis inhibited by bcl2, which together carry
out the tumor suppressor function. Since genetic alterations of p53 are
frequently observed in gastric cancers, the expression of p21 and bcl2 may be
altered in gastric carcinogenesis. We therefore analyzed normal mucosa,
nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human
stomach using immuno-histochemistry, polymerase chain reaction-single-strand
conformation polymorphism and DNA sequencing. In normal gastric mucosa, the
expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression
was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined
to only a few regenerative epithelial cells of the mucous neck region. In chronic
gastritis or intestinal metaplasia, topographic expression became more obvious.
This topographic expression was altered in hyperplastic polyps and adenomas.
Hyper-plastic polyp showed an increased p21 and p53 expression with no bcl2
expression. Where as bcl2 expression increased and extended up parabasal and
superficial dysplastic epithelium, p21 expression increased and was limited to
surface dysplastic epithelium. Weak p53 expression was in full thickness of
dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in
intestinal type of carcinoma. In carcinomas, this topography was abrogated, but
p53 mutation (36%) was present. There was no relationship between p53, p21 and
bcl2 expression. As a result, in normal gastric epithelial cells, there was a
precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression
that becomes disordered during neoplasia. These results suggest that altered cell
cycle and apoptosis control by wild-type p53 and its mediators appears to be an
early event in gastric carcinogenesis that may facilitate tumor progression.
PMID- 9651944
TI - Prognosis in lower lip squamous cell carcinoma: assessment of tumor factors.
AB - We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma
(LLSCC) in order to identify any variables which might predict the development of
lymph node metastases. The cases were divided into 38 tumors without metastases
(group I) and 16 tumors with lymph node metastases (group II). The following
factors were investigated: tumor size, histologic grading maximal thickness,
perineural invasion, DNA ploidy and PCNA expression. In conclusion, we found that
LLSCC greater than 2 cm in diameter, with histological grading G3-G4, thickness
of more than 6 mm, DNA aneuploidy and high PCNA expression (PCNA LI > 0.48), were
at high risk for the development of lymph node metastases.
PMID- 9651945
TI - DNA ploidy pattern in papillary renal cell carcinoma. Correlation with
clinicopathological parameters and survival.
AB - Papillary renal cell carcinoma (PRCC) is a less frequent histomorphologic variant
of renal cortical carcinoma (RCC). Morphologically, PRCC differs from other forms
of RCC in that it is associated with frequent tumor infiltration by macrophages
and lymphocytes, and a tendency for central necrosis and cystic change. Follow-up
data revealed that survival rates are higher among patients with PRCC than among
patients with other forms of RCC. The authors explore the DNA content in a series
of PRCC and correlate the findings with nuclear grade, pathological stage and
survival. Using Flow Cytometry, we analysed the DNA ploidy pattern of 37 paraffin
embedded PRCC. At least 3 tumor fragments were analysed in each case. To obtain
the reference diploid standard, the non-tumor renal tissue from the same case was
added to the solution. Tumor ploidy was classified as diploid and aneuploid. The
degree of DNA content abnormalities was given by the DNA Index (DI). An aneuploid
DNA profile was found in 65% of the tumors. 25% of the aneuploid tumors presented
near diploid peaks (1.10 < DI < 1.30; low degree aneuploidy), 25% were
hyperdiploid, while 22% had a hypodiploid profile (DI < 0.90). A homogeneous DNA
ploidy pattern was observed in 25 tumors (68%), while there was intratumoral
heterogeneity in 12 tumors (32%). Patients with aneuploid DNA patterns had high
grade/stage tumors and died at the end of the follow-up period, while patients
with diploid/near diploid profiles had low grade/stage tumors and survived.
However, the multi-way analysis of variance performed in order to investigate the
prognostic significance of ploidy pattern against tumor stage and grade showed a
highly significant main effect of ploidy pattern. Moreover, the patients with
hypodiploid DNA profile presented the worst prognosis. These results suggest that
the DNA profile of PRCC is a highly significant prognostic index.
PMID- 9651946
TI - Expression of monocyte chemotactic protein-1 in human invasive ductal breast
cancer.
AB - Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage
infiltration of tumor tissue. Tumor associated macrophages (TAMs) are a
population of mononuclear-phagocytic cells, which can express complex functions
related to tumor biology. The present study was designed to analyse the
expression of MCP-1 in parenchymal and stromal elements on frozen sections of 27
breast invasive ductal carcinomas not otherwise specified (NOS) by
immunohistochemistry. The expression of MCP-1 in tumor parenchyma and the degree
of tumor differentiation were assessed. MCP-1 was detected in the parenchyma in
15 of 27 ductal carcinomas. Positive immunoreactivity manifested as diffuse,
homogeneous, moderate or strong, cytoplasmic staining, confined to tumor
epithelium. Generally, MCP-1-negative tumors tended to be well differentiated,
while chemokine-positive tumors exhibited a low level of differentiation. MCP-1
immunoreactivity was also present in TAMs (CD68 positive cells) in 23 of 27
tumors, and in endothelial cells in 11 of 27 tumors. These results indicate that
parenchymal and, more variably, stromal elements of human invasive ductal
carcinomas NOS can express MCP-1 in vivo. Additionally, these findings suggest
that MCP-1 expression in tumor parenchyma is correlated with the histological
grade of ductal invasive breast carcinoma.
PMID- 9651947
TI - Warthin-like tumor of the thyroid: a papillary carcinoma with mitochondrion-rich
cells and abundant lymphoid stroma. A case report.
AB - Papillary carcinoma is the most common form of thyroid carcinoma and, generally,
it has a more favorable prognosis than other carcinoma types, although diverse
variants or subtypes have been described, some of which appear to have a less
favorable prognosis. Recently, a new variant, the so-called "Warthin-like tumor"
or "tall-cell variant with extensive lymphocytic infiltration of papillary
thyroid carcinoma" with behavior similar to the usual papillary carcinoma, has
been described. We present a case with the cytohistological pattern of "Warthin
like tumor" of the thyroid. Immunohistochemistry revealed reactivity at the
epithelium lining papillae for antimitochondrial 113-I antibody and also
membranous positivity for CD15 (Leu M1). Lymphoid stroma showed an immunoprofile
similar to chronic lymphocytic thyroiditis. These findings point to the
consideration of "Warthin-like tumor" as being a hybrid neoplasm between the tall
cell variant and oxyphilic papillary carcinoma associated to a lymphoid-rich
stroma.
PMID- 9651948
TI - Muscular hamartoma of the breast. Case report and review of the literature.
AB - Muscular hamartoma (MH) is a rare tumor-like lesion of the breast, and only 22
cases have been reported in the literature. We report an additional case of MH of
the breast, giving a new immunocytochemistry-based insight into the histogenesis
of the smooth muscle component. The expression of CD34 antigen in smooth muscle
cells suggested that MH originates from stromal cells via leiomyomatous
metaplastic changes. This hypothesis was supported by the evidence that stromal
cells in the normal parenchyma nearby the hamartoma were positive for CD34
antigen and, focally, also positive for smooth muscle markers (alpha-smooth
muscle actin and desmin). A complete list of differential diagnoses and a review
of the literature on the topic are provided. Although the use of the term
"muscular hamartoma" could be considered inappropriate because of the absence of
smooth muscle tissue in the normal breast, the authors underline that this
designation can be easily accepted if the histogenesis of the heterologous
component is regarded as a result of a stromal cell metaplastic change.
PMID- 9651949
TI - Rhabdomyosarcoma with rhabdoid-like features.
AB - We describe an unusual case of a rhabdomyosarcoma (RMS) in that it had rhabdoid
like cells histologically and occurred in a female who had undergone bone marrow
transplantation for chronic myelogenous leukemia. The tumor was composed of
loosely cohesive cells with abundant eosinophilic cytoplasm and exhibited PAS
negative paranuclear inclusions. The tumor cells had positive vimentin, muscle
specific actin, sarcomeric actin and desmin immunoreactivity. Ultrastructurally,
the tumor cells contained aggregates of thin and thick filaments. In situ
hybridization did not detect human papillomavirus or cytomegalovirus DNA, or EBV
DNA or RNA. The tumor fulfilled the current criteria for a diagnosis of RMS;
however, it could not be further classified. The tumor appears to have a good
prognosis as there has been no evidence of recurrence five years after resection.
As this is the first case report, to our knowledge, of this type of tumor
following bone marrow transplant, the significance of this association is not yet
clear.
PMID- 9651950
TI - Moyamoya disease with concurrent von Recklinghausen's disease and cerebral
arteriovenous malformation.
AB - We present a rare autopsy case of von Recklinghausen's disease with Moyamoya
vessels and arteriovenous malformation. A 58-year-old female patient suffered
from dysarthria and dysphagia. On examination, Parkinson's signs, pseudobulbar
palsy, and muscular weakness of the left extremity and pyramidal tract signs were
observed. An enhanced brain computed tomography revealed abnormal high-density
network vessels at the thalamus and midbrain. By cerebral angiography, the
following changes were observed; occlusion of the right internal carotid artery
at the bifurcation, and abrupt narrowing and occlusion of the left internal
carotid artery at the bifurcation and siphon. A lateral vertebral arteriography
revealed telangiectasia at the basilar tip. The patient died of pulmonary
thromboembolism at age 61. The vessels of the circle of Willis were hypoplastic.
The optic nerves, infundibulum and mammillary body were covered with a large
number of ectastic vessels. Arteriovenous malformations were observed in the
bilateral occipital lobes. Histopathologically, the elastic lamina of Moyamoya
vessel was conspicuously wavy and often duplicated or triplicated, and
discontinued occasionally. Discontinuity of the elastic lamina of the perforating
arteries and circumferential arteries supplied by the middle cerebral artery
(MCA), anterior CA (ACA) and posterior CA (PCA), was also occasionally observed.
It is likely that the Moyamoya vessels in this patient were compensatorily formed
by congenital hypoplasia of the internal artery, MCA, ACA and PCA.
PMID- 9651951
TI - Well differentiated cerebellar tissue within a mature cystic teratoma.
AB - We describe the case of a 27 year-old woman presenting with acute abdominal pain
due to torsion of a right ovarian cyst. Histopathological examination of the
excised lesion revealed a mature cystic ovarian teratoma consisting primarily of
a highly organized cerebellar component, an exceedingly rare finding. The
possibility of a malignant neuroepithelial tumor arising from immature precursor
cells within this neural tissue justifies complete excision of such lesions.
PMID- 9651952
TI - A two-dimensional array for B-mode and volumetric imaging with multiplexed
electrostrictive elements.
AB - A 2:1 multiplexed 2-D array has been developed that has a sparse element pattern
designed for real time volumetric imaging and an alternate element pattern
designed for B-mode imaging. For volumetric imaging, a small aperture was used to
provide a wide transmit beam, allowing multiple beams to be received
simultaneously. For B-mode imaging, a larger aperture with a more narrow transmit
beam was used to improve image quality. Sparse random element patterns were
evaluated by beamplot and cyst image simulations. Using the alternate element
pattern for B-mode imaging, simulated cyst contrast was improved by 28%. The
multiplexed transducer was fabricated using an electrostrictive material in which
array elements were activated and deactivated by a dc bias field. The transducer
had a 3.4 MHz center frequency with 46% bandwidth, which was consistent with KLM
simulations. The high dielectric constant of the electrostrictive material
resulted in an element clamped capacitance of 14.3 pF versus 2 pF for a
convention PZT element. An output off isolation of -35 dB was measured for
transmit and -61 dB for receive. The array was integrated with the volumetric
scanner and used to make real time images of a cyst phantom. The images showed
improved cyst contrast using the alternate aperture for B-mode imaging.
PMID- 9651953
TI - Spatial compounding in 3D imaging of limbs.
AB - Effects of spatial compounding on image resolution and speckle noise are studied.
Using computer simulation, it is shown that spatial compounding using averaged
reconstruction can significantly improve lateral resolution while slightly
deteriorate axial resolution. The amount of net resolution improvement depends
mainly on the compound angle, but is insensitive to the number of component
images used in compounding. While the fact that spatial compounding can
effectively reduce speckle noise is well known, the analysis in this paper
indicates that to maximize speckle reduction, the component echo amplitudes must
meet two conditions: to be mutually independent and to have the same mean power.
These findings provide useful guidelines for the analysis and optimization of the
performance of an ultrasound scanning system that has been specially developed
for imaging residual limbs.
PMID- 9651954
TI - Spectral analysis of demodulated ultrasound returns: detection of scatterer
periodicity and application to tissue classification.
AB - Ultrasound returns from tissue display variations in amplitude on several spatial
scales. Although large-scale variations result from factors such as attenuation,
variations on smaller scales are caused by tissue characteristics such as
variations in scatterer spacing and reflectance. These small scale variations
cause a corresponding variation in the amplitude of the ultrasound return. A
simple and direct method for detecting and quantifying periodicity in these
variations in the presence of attenuation is described. The radiofrequency
ultrasound return is first demodulated by full-wave rectification. The normalized
power spectrum of the demodulated return then yields an index that we call the
relative Fourier energy. Both computer simulations and in vitro experiments were
performed in order to study how relative Fourier energy performed in
discriminating between periodic and random scatterer distributions. Computer
simulations demonstrated significant differences between the returns from
periodic and random scatterer distributions. Ultrasound returns from aortic
tissue yielded a relative Fourier energy index that was significantly different
between normal vs. atherosclerotic tissue (normal: 0.868 +/- 0.076, mean +/-
s.d., fibrofatty plaque: 0.705 +/- 0.109, p < 0.01 vs. normal, calcified plaque:
0.753 +/- 0.078, p < 0.01 vs. normal). In contrast, no difference was found in
comparisons of overall reflectance.
PMID- 9651955
TI - High resolution low frequency ultrasonic tomography.
AB - Ultrasonic reflection tomography results from a linearization of the inverse
acoustic scattering problem, named the inverse Born approximation. The goal of
ultrasonic reflection tomography is to obtain reflectivity images from
backscattered measurements. This is a Fourier synthesis problem and the first
step is to correctly cover the frequency space of the object. For this inverse
problem, we use the classical algorithm of tomographic reconstruction by
summation of filtered backprojections. In practice, only a limited number of
views are available with our mechanical rig, typically 180, and the frequency
bandwidth of the pulses is very limited, typically one octave. The resolving
power of the system is them limited by the bandwidth of the pulse. Low and high
frequencies can be restored by use of a deconvolution algorithm that enhances
resolution. We used a deconvolution technique based on the Papoulis method. The
advantage of this technique is conservation of the overall frequency information
content of the signals. The enhancement procedure was tested by imaging a square
aluminium rod with a cross-section less than the wavelength. In this application,
the central frequency of the transducer was 250 kHz so that the central
wavelength was 6 mm whereas the cross-section of the rod was 4 mm. Although the
Born approximation was not theoretically valid in this case (high contrast), a
good reconstruction was obtained.
PMID- 9651956
TI - Multiple-transducer scheme for scanning tomographic acoustic microscopy using
transverse waves.
AB - We propose a new type of multiple-transducer scheme with functions of multiple
angle and multiple-frequency tomography for scanning tomographic acoustic
microscopy (STAM) using transverse waves. We review the data acquisition system
and mode conversion of the acoustic waves for STAM and the multiple-angle and
multiple-frequency tomography. Our multiple-transducer scheme has three
insonification angles and three resonance frequencies in order to operate, in the
transverse wave mode, multiple-angle and multiple frequency tomography for STAM.
In order to evaluate the performance of our transducer scheme, we have simulated
tomographic reconstruction with a back-and-forth propagation algorithm.
Simulation results show that our multiple-transducer scheme is capable of
obtaining good resolution with transverse wave mode and multiple-frequency
tomography. We also show that our multiple-transducer scheme is an efficient
rotation tool for a number of projections.
PMID- 9651957
TI - Blood flow through the ductus venosus in human fetus: calculation using Doppler
velocimetry and computational findings.
AB - The present study was performed to assess a new method to calculate the blood
flow rate through the ductus venosus (DV) in normal human fetuses using available
echo-Doppler data. Color Doppler sonographic unit was used to study DV flow in 26
normal fetuses between 20 and 36 wk of gestation. Maximal velocity flow tracings
and vessel diameters were obtained at the isthmic and the outlet portion of the
DV. Time-averaged velocities in the DV were measured from the recorded tracings.
The velocity distribution in the two investigated cross-sectional areas of the DV
was evaluated by means of computational model simulations and the velocity shape
coefficients h(in) and h(out), (i.e., the ratios between the maximal and mean
spatial velocities) were calculated as a function of vessel geometry. These
values allowed us to convert maximal Doppler velocities into mean spatial
velocities for each fetus. Blood flow rate was evaluated both at the isthmus and
at the outlet of the vessel by means of two formulae based on the
ultrasonographic measures and the results of the computational model. The value
of the DV blood flow rate was calculated as the average between the results
provided by the two formulae. The velocity distributions both at the isthmus
(h(in) = 0.677 +/- 0.040) and the outlet (h(out) = 0.374 +/- 0.072) of the ductus
are skewed toward the inner wall. Ductus geometry, i.e., the isthmic/outlet
diameter ratio, affects the shape of the velocity profiles in the vessel,
particularly that at the outlet. The coefficients of variation for repeated
measurements of the ductal diameters were 9.5 +/- 7.7% and 6.7 +/- 4.9% at the
isthmus and the outlet, respectively. The two formulae gave values statistically
identical for the time-average blood flow rate (36.3 +/- 22.1 vs. 39.4 +/- 24.0
mL/min; R = 0.946, p = NS). The mean percent difference between the results of
the two formulae was 7.1%. Thus, in human fetuses, the use of the two formulae
based on both Doppler data and computational model simulations makes it possible
to calculate the ductal flow rate. When the difference between the calculations
of the two formulae exceeds the 30% of their average value, it is convenient to
adopt the flow rate value calculated at the isthmus instead of the average of the
two measures. The measurements at the outlet of the ductus were more difficult to
obtain, and the spatial velocity profile at the outlet depends more on the DV
anatomy.
PMID- 9651958
TI - Ultrasonographic characterization of carotid plaques.
AB - The composition of atherosclerotic plaques in the carotid artery is assumed to be
related to the development of neurological symptoms. The echo patterns produced
by B-mode ultrasound may be of use in the assessment of the plaques' composition.
It is suggested that fibrotic and "stable" plaques are more echogenic than
lipid/hemorrhagic and echolucent or "unstable" plaques. B-mode ultrasound
procedures were performed 1 day prior to surgery on 46 consecutive
endarterectomies. Two observers assessed the plaques according to their echo
pattern and echogenicity and sorted them into three categories: 1) predominantly
echolucent, 2) heterogeneous, and 3) predominantly echogenic. The intraobserver
agreement was moderate (kappa = 0.44) and the interobserver agreement low (kappa
= 0.38). Furthermore, subjective categorization of plaque types resulted in type
1 plaques being as fibrotic as type 2 or 3 plaques. We conclude that B-mode
ultrasound and subsequent subjective categorization of atherosclerotic plaques
cannot adequately determine the volume of fibrosis or lipids within the plaque.
PMID- 9651959
TI - Contrast-enhanced sonography of tumor neovascularity in a rabbit model.
AB - This project was designed to detect the development of tumor neovascularity and
determine if intravenous microbubble contrast improves visualization of otherwise
undetectable tumors in an animal model. VX-2 carcinoma was implanted into one
thigh of 10 New Zealand white rabbits. Tumors were assessed without and with
contrast at 1- to 4-day intervals from day 3-19 postimplantation, using gray
scale, color flow, pulse Doppler and power Doppler imaging. Tumor vascularity was
compared with the contralateral thigh muscle, so each animal was its own control.
Contrast injection improved visualization of tumor neovascularity. Early tumors
had homogeneous vasculature but, with time, the centers became less vascular,
while the periphery increased. Following contrast injection, color gain was
decreased by 40% without compromising color intensity. Neovascularity was
detected by contrast injection before the tumor could be palpated or visualized
by gray scale. Based on these data, we conclude that enhancement of
neovascularity by intravenous contrast permits earlier detection and improved
visualization of soft tissue tumors in rabbits.
PMID- 9651960
TI - Effects of a sudden flow reduction on red blood cell rouleau formation and
orientation using RF backscattered power.
AB - In most studies that were aimed at evaluating the kinetics of red blood cell
(RBC) aggregation, human blood was initially circulated at a high shear rate to
disrupt the aggregates, and measurements were performed following a complete flow
stoppage, during the process of rouleau formation. However, it is known that a
very low shear rate can enhance the formation of aggregates, as demonstrated by
the modal relationship of the shear-rate dependence of RBC aggregation. The
objective of the present study was, thus, to evaluate the influence of sudden
flow reductions compared to a complete flow stoppage on the kinetics of rouleau
formation, using ultrasound backscattering. Horse blood models, characterized by
different aggregation levels, were obtained by diluting the plasma with a saline
solution in different proportions. Blood was circulated in a 12.7-mm vertical
tube at a flow rate of 1250 mL min-1 (prereduction flow rate) to disrupt the
aggregates. The ultrasound radiofrequency (RF) signal was recorded from the
center of the tube following different levels of sudden flow reduction or
complete stoppage (postreduction flow rate). All measurements were performed over
2 min, using a 10-MHz transducer. No power increase was observed after complete
flow stoppage. For postreduction flow rates varying between 20 and 160 mL min-1,
the backscattered power increased proportionally with the kinetics of RBC
aggregation. The echo buildup was also faster and stronger when the postreduction
flow rate was increased. An unexpected pattern of variation of the backscattered
power was found for horse RBCs characterized by high kinetics of rouleau
formation. The power increased rapidly to a plateau, followed by another rapid
increase and another plateau. Rouleau formation, random disorientation and
reorientation were postulated to explain the phasic power increases observed.
PMID- 9651961
TI - Onset delay of acoustic second harmonic backscatter from bubbles or microspheres.
AB - A well-known method of enhancing blood detectability in ultrasound imaging of
tissues detects the second harmonic of the incident radiation, which is generated
by ultrasound contrast agents in the form of bubbles or microspheres that may
have been injected into the blood. We report here a delay in the onset of the
backscattered second harmonic with respect to the backscattered first harmonic
for these agents. This effect, which should limit the axial resolution attainable
with harmonic imaging, is investigated by simulation as well as experiment, and
its dependence on the incident ultrasonic amplitude and microsphere parameters is
established.
PMID- 9651962
TI - Acoustic modeling of shell-encapsulated gas bubbles.
AB - Existing theoretical models do not adequately describe the scatter and
attenuation properties of the ultrasound contrast agents Quantison and Myomap. An
adapted version of the Rayleigh-Plesset equation, in which the shell is described
by a viscoelastic solid, is proposed and validated for these agents and Albunex.
The acoustic transmission and scattering are measured in the frequency band from
1-10 MHz. The measured transmission is used to estimate two parameters, the
effective bulk modulus, Keff, describing the elasticity, and the friction
parameter, SF, describing the viscosity of the shell. For the scattering, the
difference between measurements and calculations is < 3 dB. For Quantison, the
effective bulk modulus is independent of the bubble diameter. For Albunex, it
increases for decreasing bubble diameter. The nonlinear response of Quantison is
minimal for acoustic pressures up to 200 kPa. For acoustic pressures above 200
kPa, the measured scattering abruptly increases. This increase reaches a level of
20 dB for an acoustic pressure of 1.8 MPa. This response cannot be predicted by
the theoretical model developed in this article.
PMID- 9651963
TI - Liquid or solid ultrasonically tissue-mimicking materials with very low scatter.
AB - A new tissue-mimicking material for ultrasound, using evaporated milk as the
primary absorption component, is described. It has very low backscatter but still
exhibits the 1540 m s-1 propagation speed and proportionality of attenuation
coefficient and frequency over the diagnostic frequency range. The material can
be produced in solid or liquid form with attenuation coefficient slopes spanning
the range 0.1-0.7 dB cm-1 MHz-1. The liquid form is useful in phantoms where
detailed beam patterns are to be determined, either involving translation of
measurement devices in the liquid or phantoms with fibers present for causing the
only detectable echoes. In the latter case, the liquid quality allows removal of
liquid with one attenuation coefficient slope and replacement with another. The
solid form may be more useful than the liquid for two reasons. First, many
simulated lesions (including ones that produce essentially no internal echoes)
can lie in the scan slice with positions extending over the entire image area
without enhancement or shadowing effects being of concern. Second, the lack of
significant backscatter from the material in the absence of added scatterers
allows the backscatter coefficient to be varied over a considerable range. A
critical result is that intrinsic material contrast between targets and
surroundings can be accurately predicted in terms of the concentrations of added
scatterers and, assuming all scatterers are of the same type, the contrast will
be completely independent of frequency. Use of the fungicide thimerosal
eliminates deterioration, and ultrasonic properties have been shown to be stable
over 2.5 years.
PMID- 9651964
TI - Characterization of elastographic noise using the envelope of echo signals.
AB - A theoretical formulation characterizing the noise performance of strain
estimation using envelope signals is presented for the cross-correlation based
strain estimator in elastography, using a modified strain filter approach. The
strain filter describes the relationship among the elastographic signal-to-noise
ratio (SNRe), sensitivity, contrast-to-noise ratio and dynamic range for a given
resolution in the elastogram, as determined by the cross-correlation window
length and window overlap. Theoretical results indicate that the envelope strain
filter noise performance (SNRe level) is about half that obtained in the ratio
frequency (RF) case (fo = 7.5 MHz). Simulation results corroborate the trend
predicted using the strain filter. Experimental SNRe vs. strain plots presented
in this article illustrate the same trend as the theoretical results. These plots
allow a quantitative comparison of the elastograms obtained with RF and envelope
signal processing. For small strains, the performance obtained using RF signals
is superior to that obtained for envelope signals (since jitter errors are
smaller due to the utilization of phase information in RF signals). However, for
large tissue strains, envelope analysis provides an accurate estimate of the
tissue strain (since envelope signal decorrelation is smaller than RF signal
decorrelation at large strains). An algorithm that combines the low-noise
characteristics of the cross-correlation analysis using RF signals at small
strains and envelope signals for estimation of large tissue strains is proposed
to improve the dynamic range in the elastogram.
PMID- 9651965
TI - Focused ultrasound modifications of neural circuit activity in a mammalian brain.
AB - The application of focused, pulsed ultrasound was studied as a method of
modifying the activity of a local neural circuit of the mammalian brain. An in
vitro hippocampal preparation was used to facilitate delivery, dosimetry and
assessment of mechanisms of ultrasound effects. Extracellular evoked potentials
were recorded from cell and dendritic layers of the rat hippocampal dentate
gyrus. Focused pulses of ultrasound with center frequency of 500 kHz and
repetition rate of 200 kHz were studied and found both to enhance and to depress
electrically evoked field potentials. The fiber volley and cell population
potentials were depressed, whereas the dendritic potential was enhanced. Results
suggest a simultaneous mechanical and thermal mechanism of ultrasound in
modifying evoked field potentials of dentate local circuits.
PMID- 9651966
TI - Application of low-intensity ultrasound to growing bone in rats.
AB - Low-intensity pulsed ultrasound recently has been shown to accelerate long bone
fracture healing, but its effect on bone growth and development is unknown. The
longitudinal growth and bone density of the femur and tibia in young rats was
measured after application of an ultrasound transducer emitting 1.5-MHz pulsed
ultrasound (30 mW/cm2, SATA) for 20 min/day. After 28 days, no length difference
was detected (< or = 2%) compared to the sham-treated leg or to unexposed
controls. Also, no significant difference in bone mineral density (BMD) of the
femur or tibia was found (< or = 6%). In a repeated experiment in which a
periosteal trauma stimulus was created in the femoral diaphysis, the ultrasound
also had no effect on growth or BMD. This results suggests that physeal bone
growth is far less sensitive to this level of ultrasound application than is
fracture repair. This may be related to the cascade of cellular events and
regulatory factors that are present after a fracture.
PMID- 9651967
TI - Effects of pulsed ultrasound on embryonic development: an in vitro study.
AB - Whole-embryo culture was used as the model system to study the effects of pulsed
ultrasound on embryonic development. Rat embryos (9.5 days old) were exposed to a
wide range of ultrasound levels at ultrasound frequencies between 1-4 MHz for 30
min in vitro. After 48 h in culture, absolute control, sham and treatment embryos
were assessed for viability, morphology, growth and development. At an ambient
temperature of 37 degrees C, no significant effects were observed for spatial
peak temporal average intensities below 4 W/cm2 or peak negative pressures below
1.9 MPa. At higher acoustic levels, there was a significant increase in the
number of nonviable embryos and the number of morphological abnormalities in
viable embryos increased. Abnormal cephalocaudal flexion and abnormal head
development were the most common gross morphological abnormalities. Both thermal
and nonthermal bioeffect mechanisms are involved.
PMID- 9651968
TI - Artificial cavitation nuclei significantly enhance acoustically induced cell
transfection.
AB - The efficiency of ultrasound-mediated gene transfection was enhanced three- to
fourfold, compared to previous results, through the use of green fluorescent
protein reporter gene, cultured immortalized human chondrocytes and artificial
cavitation nuclei in the form of Albunex. Cells were exposed to 1.0-MHz
ultrasound transmitted through the bottom of six-well culture plates containing
immortalized chondrocytes, media, DNA at a concentration of 40 micrograms/mL and
Albunex at 50 x 10(6) bubbles/mL. Transfection efficiency increased linearly with
ultrasound exposure pressure with a transfection threshold observed at a spatial
average peak positive pressure (SAPP) of 0.12 MPa and reaching about 50% of the
living cells when exposed to 0.41 MPa SAPP for 20 s. Adding fresh Albunex at 50 x
10(6) bubbles/mL prior to sequential 1-s, 0.32- or 0.41-MPa exposures increased
transfection with each exposure, reaching 43% transfection after four exposures.
Efficient in vitro and in vivo transfection now appear possible with these
enhancements.
PMID- 9651969
TI - Gosling's Doppler pulsatility index revisited.
AB - In Doppler sonography, the physiological meaning of Gosling's pulsatility index
(PI) as a measure of downstream resistance is still under dispute. We deliver the
theoretical derivation of its physiological significance. We present a
mathematical model based on the linked theories of critical closing pressure
(CCP) and cerebrovascular impedance, verified in preterm neonates. Mathematical
transformation results in a series of equations interrelating several
physiological parameters. Instead of indicating cerebrovascular resistance, PI is
linked to the ratio of cerebrovascular impedances at the heart rate and at zero
frequency. Next to arterial blood pressure, CCP is the principal determinant of
PI. PI is identical to the ratio of the alternate and the direct component of the
effective driving force. Thus, PI has no distinctive physiological meaning by
itself. At present, our model is confined to physiological conditions where the
lowest velocity is the end diastolic, and always more than zero.
PMID- 9651970
TI - Influence of ECG-triggered data acquisition on reliability for carotid plaque
volume measurements with a magnetic sensor three-dimensional ultrasound system.
AB - Three-dimensional (3D) ultrasound reconstructions of the carotid arteries are
based on multiple sections of two-dimensional data. Some 3D systems use an
electrocardiography (ECG)-triggered data acquisition for 3D reconstructions of
pulsatile vessels such as carotid arteries. No systematic comparison of 3D data,
acquired with and without ECG triggering, has been reported. We used a new
magnetic sensor system allowing freehand scanning for data acquisition. Our aim
was to test the effect of ECG triggering on the reliability of plaque volume
measurements in the carotid arteries. Data acquisition in the carotid arteries in
25 patients (one plaque from each patient) was performed using two different
procedures for data acquisition: 1) a magnetic sensor system for a data
acquisition without ECG-triggering, and 2) a magnetic sensor system with ECG
triggered data acquisition. All plaque volumes were measured using manual tracing
of the outlines of the plaques. The following reliability data (mean values) were
obtained: magnetic sensor system without ECG triggering: intrareader variability
13.3%, interreader variability 16.7%, follow-up variability 16.3%; magnetic
sensor system with ECG triggering: intrareader variability 4.6%, interreader
variability 4.5%, follow-up variability 5.2%. Carotid plaque volume measurements
obtained using a magnetic sensor system with freehand scanning and ECG triggering
is highly reliable. ECG triggering is necessary, because a magnetic sensor system
without ECG triggering resulted in reduced reliability for plaque volume
measurements.
PMID- 9651971
TI - Color flow mapping.
PMID- 9651972
TI - Laryngeal paralysis: an introduction.
PMID- 9651973
TI - Laryngeal paralysis: an emergency management.
PMID- 9651974
TI - Laryngeal paralysis: surgical solutions.
PMID- 9651975
TI - The chronic ear: diagnosis and medical management.
PMID- 9651976
TI - Tumors of the external ear.
PMID- 9651977
TI - The ear: surgery for chronic otitis.
PMID- 9651978
TI - Pleural effusion: recent advances in diagnosis and treatment.
PMID- 9651979
TI - Surgical diseases of the lung and chest wall: new development in the treatment of
pneumothorax.
PMID- 9651980
TI - Surgical oncology.
PMID- 9651981
TI - Biopsy principles.
PMID- 9651982
TI - Abdominal tumors.
PMID- 9651984
TI - Skin tumors and mast cell cancer.
PMID- 9651983
TI - Soft tissue sarcomas.
PMID- 9651985
TI - Osteosarcoma.
PMID- 9651986
TI - Canine hip dysplasia: pathogenesis, diagnosis, and genetic control.
PMID- 9651987
TI - Triple pelvic osteotomy (TPO) for the treatment of hip dysplasia.
PMID- 9651988
TI - Fractures and luxations of the elbow.
PMID- 9651989
TI - Surgical treatment of elbow dysplasia.
PMID- 9651990
TI - Professional periodontal therapy and home care.
PMID- 9651991
TI - Endodontic treatment.
PMID- 9651992
TI - Adhesive dentistry with direct restorative materials.
PMID- 9651993
TI - Understanding feline diabetes: pathogenesis and management.
PMID- 9651994
TI - Anemia in the dog and cat.
PMID- 9651996
TI - Immune-mediated hemolytic anemia.
PMID- 9651995
TI - Abnormal osmotic fragility of erythrocytes in dogs and cats.
PMID- 9651997
TI - Disorders of hemostasis.
PMID- 9651998
TI - Congenital (hereditary) clotting disorders in the dog.
PMID- 9651999
TI - Immune-mediated thrombocytopenia.
PMID- 9652000
TI - Diagnosis of liver disease in companion animals.
PMID- 9652001
TI - Reactive hepatopathies and chronic hepatitis in the dog.
PMID- 9652002
TI - Treatment of chronic hepatitis and management of biliary tract disorders.
PMID- 9652003
TI - Injection anesthesia in companion animals.
PMID- 9652004
TI - Inhalational anesthesia.
PMID- 9652005
TI - Resuscitation.
PMID- 9652006
TI - Anesthesia of patients with liver or renal disease.
PMID- 9652007
TI - Cardiac disease and companion animal anesthesia.
PMID- 9652008
TI - Emergency management ... and what's next?
PMID- 9652009
TI - Fluid therapy in companion animal medicine.
PMID- 9652010
TI - Catheters, drains, and tubes.
PMID- 9652011
TI - Introduction to avian practice.
PMID- 9652012
TI - Nursing avian patients.
PMID- 9652013
TI - Avian nutrition.
PMID- 9652014
TI - Avian anesthesia.
PMID- 9652015
TI - Avian radiology and endoscopy.
PMID- 9652016
TI - Avian respiratory disease.
PMID- 9652017
TI - Avian orthopedics.
PMID- 9652018
TI - Avian soft tissue surgery.
PMID- 9652019
TI - Guidelines for obesity management in companion animals.
PMID- 9652020
TI - Nutrition and gastrointestinal disease.
PMID- 9652021
TI - Nutrition, metabolism, and cancer.
PMID- 9652022
TI - Diet and kidney or liver failure.
PMID- 9652023
TI - Metabolic needs of the injured: enteral feeding support of dogs and cats.
PMID- 9652024
TI - Nutritional uniqueness of cats.
PMID- 9652025
TI - A new method of tube esophagostomy in cats.
PMID- 9652026
TI - Ultrasonography: principles, indications, and limitations.
PMID- 9652027
TI - Ultrasonography of the cranial abdomen: liver, spleen, pancreas, and
gastrointestinal tract.
PMID- 9652029
TI - Radiographic diagnosis of tumors: bone, lung and abdominal tumors.
PMID- 9652028
TI - Ultrasonography of the caudal abdomen: urogenital tract, and adrenals.
PMID- 9652030
TI - The role of molecular genetics in the diagnosis of diseases in companion animals:
an introduction.
PMID- 9652031
TI - DNA analysis in paternity testing of dogs and cats.
PMID- 9652032
TI - DNA analysis in diagnosis of von Willebrand disease in dogs.
PMID- 9652033
TI - Molecular diagnosis of copper toxicosis in Bedlington terriers.
PMID- 9652034
TI - Toxocara infections in dogs and cats and public health implications.
PMID- 9652035
TI - Transsphenoidal hypophysectomy for the treatment of pituitary-dependent
hyperadrenocorticism in dogs.
PMID- 9652036
TI - Modulation of the GABAergic tone by benzodiazepine receptor ligands in chronic
hepatic encephalopathy in the dog.
PMID- 9652037
TI - Studies on the function of the urethra and bladder in continent and incontinent
female dogs.
PMID- 9652038
TI - Pharmacokinetics of marbofloxacin in renal impairment in the dog.
PMID- 9652039
TI - Cardiomyopathy in the Irish wolfhound. A clinical study of 393 dogs by electro-
and echocardiography and radiology.
PMID- 9652040
TI - EEG-burst-suppression-controlled propofol anesthesia in the dog.
PMID- 9652041
TI - Indicators of the genetic variation in five dog breed populations in The
Netherlands.
PMID- 9652042
TI - Immunophenotyping of skin-infiltrating T-cell subsets in dogs with atopic
dermatitis.
PMID- 9652043
TI - Fourteen week clinical evaluation of an oral antioxidant as a treatment for
osteoarthritis secondary to canine hip dysplasia.
PMID- 9652044
TI - An alternative premedication and induction regime for cats with a decreased
cardio-vascular reserve.
PMID- 9652045
TI - Plasma ACE inhibition by five different ACE inhibitors.
PMID- 9652046
TI - Progressive destruction of the elbow joints in a dog with leishmaniasis.
PMID- 9652047
TI - Hyperadrenocorticism caused by an adrenal carcinoma in a parrot.
PMID- 9652048
TI - Canine intestinal leiomyosarcoma.
PMID- 9652049
TI - Polycystic kidney disease in cats.
PMID- 9652050
TI - Successful treatment of neosporosis in an adult dog.
PMID- 9652051
TI - A retrospective evaluation of 51 dogs with insulinoma.
PMID- 9652052
TI - Differentiating infection from vaccination in foot-and-mouth disease.
PMID- 9652053
TI - Serodiagnostic strategy for estimation of foot-and-mouth disease viral activity
through highly sensitive immunoassays using bioengineered nonstructural proteins.
PMID- 9652054
TI - Antibody to the nonstructural proteins of foot-and-mouth disease virus in
vaccinated animals exposed to infection.
AB - Cattle which have been infected with foot-and-mouth disease (FMD) virus can be
differentiated from those that have been vaccinated on the basis of the detection
of antibody to one or more of the non-structural (NS) proteins of the virus.
Cattle which have been protected by vaccination can become persistently infected
with FMD virus (FMDV) without ever showing clinical signs. Vaccinated, protected
cattle which are persistently infected cannot be distinguished from animals that
merely have been vaccinated on the basis of serological tests for antibody to the
structural proteins of FMDV. Sera were collected from groups of cattle for
varying periods after exposure to infection under experimental conditions. On the
basis of isolation of virus from probang samples collected during the course of
the experiments it was possible to classify the cattle according to the following
criteria; naive, infected and eliminated the virus (convalescent), infected and
persistently infected with FMDV (carriers), vaccinated alone, vaccinated and
either convalescent or carrier. Sera were examined for antibody to the NS
proteins Lb, 2C, 3A, 3D, and 3ABC by an indirect profiling ELISA using E. coli
expressed fusion proteins as antigens. Considerable variation was observed in the
antibody response to NS proteins of both naive and vaccinated animals following
infection. The extent of individual variation was so great that convalescent
animals could not be differentiated from carrier animals on the basis of their
antibody response to any of the NS proteins examined. The majority of vaccinated,
protected animals showed an antibody response to NS proteins, particularly 3ABC,
following exposure to infection. However, the carrier state was demonstrated in
some vaccinated, protected animals in which no antibody response to any of the NS
proteins could be detected. The detection of antibody to NS proteins can
therefore be used on a group, or herd, basis to detect circulation of virus in a
vaccinated population but further investigations in the field are required to
determine the sampling level necessary for statistical acceptance. On an
individual animal basis, however, freedom from antibody to NS proteins in a
vaccinated animal, or an animal of unknown history, does not necessarily imply
that the animal is free from infection with FMD virus and, furthermore, the titre
of antibody to NS proteins is not a useful predictive measure of whether or not
an infected animal has successfully eliminated the virus.
PMID- 9652055
TI - Differentiating foot-and-mouth disease virus-infected from vaccinated animals
with baculovirus-expressed specific proteins.
AB - We had shown in preliminary studies with a small number of animals that
antibodies against 2C could be detected in cattle and pigs which had been
infected with FMDV but not in animals which had been vaccinated against the
disease. To determine whether this test was generally applicable, sera from
several hundred animals which had been vaccinated with different products in many
countries have been tested in an ELISA using baculovirus expressed 2C. Our
results show that only 1-2% of the sera gave a positive reaction by this method.
In contrast, 100% of sera from convalescent animals gave a positive reaction. To
be useful in differentiating between convalescent and vaccinated animals it is
necessary to know how long these antibodies can be detected by our ELISA. We have
determined the levels of antibodies against 2C and also other virus-specific
proteins which are present in cattle and pigs following infection with FMDV. Our
results show that levels of anti-3ABC antibodies could be detected by ELISA with
baculovirus-expressed protein up to one year after infection. In contrast, the
levels of anti-2C antibodies fell more rapidly than those against 3ABC indicating
that the latter protein may be preferable for detecting convalescent animals.
Nevertheless, we envisage that the final test format should include several virus
specific proteins to determine accurately the immune status of an animal.
PMID- 9652057
TI - Blocking ELISAs using the FMDV non-structural proteins 3D, 3AB, and 3ABC produced
in the baculovirus expression system.
PMID- 9652056
TI - Cattle response to foot-and-mouth disease virus nonstructural proteins as
antigens within vaccines produced using different concentrations.
AB - Four groups of ten nine-month-old Nelore heifers were used for this study. Each
group received one of four foot-and-mouth disease (FMD) trivalent vaccines for
the duration of the experiment. The four vaccine formulations (Normal, 2X, 4X and
8X) differed in 140S content to determine the serological reactivities to FMD
virus (FMDV) nonstructural proteins 2C, 3ABC and 3D. Vaccination was by the
intramuscular administration of vaccine on day 0, 180 and 360. Bleedings were
done at 30 days post vaccination (dpv), 90 dpv, 30 days post revaccination (dpr),
90 dpr, and 30 days post third administration (dprr). There was a general
tendency to have higher mean 3D responses with increased vaccine application but
not with increased concentration of antigen. With 2C and 3ABC this tendency was
not seen, neither with repeated application of vaccine nor with increased antigen
concentration. All individual animal observations to 2C and 3ABC remained within
three standard deviations of the average observed for naive bovids. Percent of
positive (PP) reactions was determined using an ELISA for nonstructural proteins
2C, 3ABC and 3D expressed in baculovirus as previously described. A value of > 25
PP to 2C or 3ABC could be considered as an indication of previous infection or of
the presence of viral activity. PP results between 18 and 25 PP suggest viral
activity and animals should be retested. Those responses below 15 PP are
suggestive of vaccination or naive status. As diagnosis in the laboratory is not
divorced from the field epidemiological scene, the intermediate zone between 10
and 20 PP should be considered and acted upon according to the overall
zoosanitary situation of that country or region and the purposes of the ongoing
FMD control efforts.
PMID- 9652058
TI - Diagnostic potential of Mab-based ELISAs for antibodies to non-structural
proteins of foot-and-mouth disease virus to differentiate infection from
vaccination.
AB - This paper summarises the development of monoclonal antibody (Mab)-based
immunoassays measuring antibodies to non-structural proteins of FMDV to
differentiate infection from vaccination. Of the three non-structural proteins
2C, 3C and 3ABC evaluated in this study, the polypeptide 3ABC was the most
immunogenic. Three ELISAs for the detection of antibodies to 3ABC were developed.
Two assays rely on the competition of test sera against either a anti-3A Mab or
against antisera to 3ABC raised in rabbits and guinea-pigs. The third, 3ABC Mat
ELISA, based on the direct binding of antibodies to the 3ABC trapped by a
specific Mab, provided the best combination of specificity and sensitivity. The
3ABC Mat-ELISA was extensively validated for cattle, either in experimental and
in field conditions, showing specificity of 99% in vaccinated and in naive cattle
and the capacity to detect silent infections in FMD-vaccinated populations. The
test showed similar specificity and sensitivity in experimentally vaccinated and
infected sheep.
PMID- 9652059
TI - Detection of cattle exposed to foot-and-mouth disease virus by means of an
indirect ELISA test using bioengineered nonstructural polyprotein 3ABC.
PMID- 9652060
TI - The possible use of native foot-and-mouth disease non-structural protein 3A in a
serological screening test.
AB - ELISA's for antibodies to non-structural proteins of foot-and-mouth disease
developed to date use recombinant proteins as antigens. To compare the antibody
response to recombinant antigen and native antigen we developed an antigen
capture ELISA for foot-and-mouth protein 3A. The concentration of 3A protein in
virus cultures was significantly higher in the cell debris than in the
supernatant, which made it possible to use proteins directly eluted from cells
separated from virus culture using Filteraid. The antigen was trapped between one
monoclonal antibody coated to the plate, and a second monoclonal antibody
conjugated with horseradish peroxidase. The reaction of the second (conjugated)
monoclonal antibody could be blocked by several post-infection sera. Further
research has to be performed to determine whether or not this method can result
in a reproducible serological test.
PMID- 9652061
TI - Serological and cellular immune responses to non-structural proteins in animals
infected with FMDV.
AB - In order to provide a rational base for the evaluation of FMDV non structural
proteins as diagnostic probes, we have performed systematic longitudinal studies
of the humoral and cellular immune responses to these proteins in animals
infected with different FMDV serotypes. Although primary antibody responses to
all the non structural proteins were observed, antibody titres were highly
variable, ranging from insignificant in some cases, to clearly positive in
others. In general, even the obvious positive responses were of short duration.
For this reasons, discrimination between infected and vaccinated cattle is only
possible at a herd level, and in our experiments the most useful target was the
non structural protein 3A, although addition of 2C and 3C would provide a more
sensitive test. As an alternative, with the major advantage of use directly on
living cattle in the field, recombinant non structural proteins were evaluated in
Delayed Type Hypersensitivity (DTH) skin tests. With this test, which measures
Th1 type cellular immune responses, the most T cell immunogenic non structural
proteins were 2B, 2C and 3D. Thus, DTH skin test could be a very useful tool to
differentiate infected from vaccinated cattle.
PMID- 9652062
TI - Aims of the FMDV-specific RT-PCR as it is performed at the BFAV, Tuebingen
laboratory.
PMID- 9652063
TI - Application of RT-PCR and nucleotide sequencing in foot-and-mouth disease
diagnosis.
PMID- 9652064
TI - RT-PCR in foot-and-mouth disease diagnosis.
AB - A RT-PCR assay for the specific detection of RNA sequences from foot-and-mouth
disease virus (FMDV) has been developed. The procedure permits also the detection
of sequences that correlate with established FMDV serotypes. A computer program
that allows selection of genotype-specific primers for RT-PCR amplification was
used for the identification of FMDV specific sequences for PCR amplification on
RNA replicase (3D) gene regions. Specific, rapid and highly sensitive detection
was achieved for a wide collection of RNA samples from FMDV types C, A and O,
either purified from tissue culture or extracted from lesions of infected
animals. Similarly, serotype-specific primers were designed to amplify the
carboxy-terminal end of the VP1 gene of FMDV types either C, A or O. The results
of PCR amplification of different FMDV RNAs using type-specific primers are in
agreement with the serological typing of the corresponding viruses. A combination
of this approach with a simplified sample processing, carried out following
direct adsorption of viral suspensions to microtiter plates, provides a rapid,
reliable method of viral diagnosis.
PMID- 9652065
TI - Detection of foot-and-mouth disease by reverse transcription polymerase chain
reaction and virus isolation in contact sheep without clinical signs of foot-and
mouth disease.
AB - Two non-vaccinated sheep were experimentally infected with FMDV and one day later
4 other sheep were brought in contact. Although the contact sheep showed no
clinical signs, serology indicated that all sheep became infected. Various
secretion samples, taken over a period of at least one month, and various tissue
samples were examined for the presence of FMDV by RT-PCR and by virus isolation.
FMDV was most often found in saliva (mouth swabs), followed by nasal secretion
and sera. Faecal material, wool and milk were less suitable. The period of
detection with the highest frequency of positive isolations was between 2 to 4
days pi for the infected sheep and between 5 to 10 days pc for the contact
animals. It was established that in subclinically infected sheep, with a very low
amount of virus present, FMD viral RNA could be detected by a sensitive RT-PCR
ELISA although virus isolation and standard RT-PCR remained negative. Moreover
there was some evidence of active spreading of FMDV from the contact sheep to two
sentinel pigs. This indicates that serologically positive contact sheep without
clinical signs may be considered as a danger for the transmission of FMDV.
PMID- 9652066
TI - Immunohistochemical localisation of a galectin from Bufo arenarum ovary.
AB - Galectins are a group of soluble animal lectins that exhibit specificity for beta
galactosides and conserve sequence homology in the carbohydrate-recognition
domain. The galectin from Bufo arenarum ovary showed a strong cross-reaction with
the lectin of 14.5 kDa purified from embryos at early blastula stage. In this
paper, we studied the immunohistochemical localisation of the galectin of 14.5
kDa from ovary of the toad B. arenarum in adult ovary sections. We also analysed
the immunohistochemical localisation of the embryonic lectin during early
development using the antiserum anti-ovary galectin. In the ovary, oocytes in the
previtellogenic stage showed strong reactivity in the nucleus and the cortex but
not in the cytoplasm. Oocytes in the stage of primary vitellogenesis exhibited a
similar pattern in the nuclear and cortical areas but showed immunostaining in
the cytoplasm. Intense nuclear staining was detected in oocytes in the stage of
late vitellogenesis and in mature oocytes, which also presented strong reactions
in the yolk platelets that completely covered the cytoplasm. In blastula embryos
the staining was found in the blastomeres, the yolk platelets and the
blastocoele. Each lectin localisation is discussed in relation to potential
biological roles in the corresponding tissues.
PMID- 9652067
TI - Non-specific currents at fertilisation in sea urchin oocytes.
AB - Using the whole-cell voltage-clamp technique to clamp sea urchin oocytes we show
that the fertilising spermatozoon triggers an inward current of -521 +/- 56.7 pA
(n = 8) at activation. Simultaneously, the plasma membrane depolarises and the
conductance increases from 23.4 +/- 1.4 to 40.6 +/- 1.2 nS (n = 8). The I/V curve
for the peak activation current is linear and the current reverses between 0 and
+20 mV, suggesting a non-specific ion current. Since injection of inositol
triphosphate induced an inward current of -1062 +/- 314 pA (n = 4), and the
current was inhibited by preloading oocytes with the calcium chelator BAPTA, the
non-specific activation current in sea urchin appears to be calcium dependent.
PMID- 9652068
TI - Ultrastructure of bovine in vitro-produced blastocysts cryopreserved by
vitrification.
AB - The objective of this study was to examine ultrastructural aspects of bovine in
vitro-produced blastocysts associated with cryopreservation by vitrification.
Morphologically good embryos were used and treated with ethylene-glycol-based
vitrification solution (VS). The untreated embryos had conventional fine
structure. The post-warming embryos treated with direct exposure to VS (one-step
procedure) showed cellular damage structurally by cryopreservation, which
included loss of microvilli, disruption of the plasma membrane, mitochondrial
changes and swelling of the endoplasmic reticulum. However, nuclei and junctional
regions seemed to be resistant to cryoinjury. In contrast, the post-warming
embryos pre-equilibrated with 10% ethylene glycol for 5 min and subsequent
exposure to VS (two-step procedure) showed less damage than those treated by the
one-step procedure. Post-warming embryos treated by the two-step procedure were
cultured in vitro for 18 h. Some embryos survived and their structures re-formed
to the former state, while other embryos showed serious injuries and could not
reconstitute the blastocoele. Three post-warming embryos treated by the two-step
procedure that survived after in vitro culture were transferred to three
recipients and one of these resulted in pregnancy. These results indicate that
cryopreservation by vitrification can damage membranous structures of the cells
of bovine embryos, the extent and nature of this damage being dependent on the
vitrification procedure.
PMID- 9652069
TI - Combined immunocytogenetic and molecular cytogenetic analysis of meiosis I
oocytes from normal human females.
AB - The microspread oocytes of three fetuses, two of 16 weeks gestation and one of 15
weeks gestation, were labelled with a combination of anti-lateral element
antiserum and a human centromere labelling auto-immune serum. The anti-lateral
element serum was found to label both asynapsed axial elements and synapsed
lateral elements strongly. Nuclei were found from leptotene to diplotene in all
three fetuses. The use of the human auto-immune serum led to the observation of
'staggered centromeres' and 'centromeric associations' as well as tightly
clustered centromeres in 'stellar nuclei'. Nuclei displaying various aberrant
features were detected. The use of antibody-labelled microspread oocytes as
substrates for fluorescence in situ hybridisation (FISH) was found to be reliably
successful only with repetitive (centromeric and telomeric) probes.
PMID- 9652070
TI - Decondensation of the mouse sperm nucleus within the interphase nucleus.
AB - Sperm nuclei incorporated into the cytoplasm (ooplasm) of fertilised mouse eggs
at the pronuclear stage remain condensed, whereas those injected into male or
female pronuclei decondense. Similarly, sperm nuclei injected into germinal
vesicles of immature oocytes or the nuclei of 2-cell embryos decondense, while
those entering the cytoplasm of these oocytes/embryos do not. These facts seem to
suggest that factors necessary for the decondensation of sperm nucleus are
present in interphase nuclei and are released into the ooplasm during nuclear
envelope breakdown. Nucleoplasmin, which is synthesised in the cytoplasm and
accumulated within the nucleus, is likely a major candidate for these factors.
PMID- 9652071
TI - Promotion of follicular antrum formation by pig oocytes in vitro.
AB - Pig oocyte-cumulus-granulosa cell complexes (OCG complexes) from pig early antral
follicles reorganise an antrum under the stimulation of FSH. The purpose of this
study was to examine the role of the oocytes in antrum formation. In the first
experiment, oocyte-cumulus complexes were removed from pig OCG complexes, and the
antrum formation of parietal granulosa cells themselves (PGs) was examined.
Antrum formation by sham-operated OCG complexes (OC/G complexes), in which the
connections between the oocytes-cumulus complexes and the parietal granulosa
cells had been disrupted, was also examined. The complexes were cultured for 8
days in collagen gels in the presence of 10 ng/ml FSH. Antra were formed in about
60% of the intact OCG complexes and the sham-operated OCG complexes, while only
20% of the PGs formed antra. In the second experiment, oocyte-cumulus complexes
in the OCG complexes were replaced by denuded oocytes (O/G complexes) or Sephadex
G-25 beads (B/G complexes) similar in diameter to the oocytes, and the two types
of complexes were cultured under the same conditions. The O/G complexes formed
antra to a similar extent as the OC/G complexes, whereas the B/G complexes
scarcely formed any antra. The histological sections showed that the granulosa
cells in the OC/G and O/G complexes were in intimate contact with each other and
retained a shape similar to those in the ovarian follicles, while the granulosa
cells in the PGs and B/G complexes became quite irregular in shape. These results
suggest that pig oocytes promote contact between the granulosa cells to induce
antrum formation in a physiological manner.
PMID- 9652072
TI - Cortical granule exocytosis is triggered by different thresholds of calcium
during fertilisation in sea urchin eggs.
AB - In sea urchin eggs, fertilisation is followed by a calcium wave, cortical granule
exocytosis and fertilisation envelope elevation. Both the calcium wave and
cortical granule exocytosis sweep across the egg in a wave initiated at the point
of sperm entry. Using differential interference contrast (DIC) microscopy
combined with laser scanning confocal microscopy, populations of cortical
granules undergoing calcium-induced exocytosis were observed in living urchin
eggs. Calcium imaging using the indicator Calcium Green-dextran was combined with
an image subtraction technique for visual isolation of individual exocytotic
events. Relative fluorescence levels of the calcium indicator during the
fertilisation wave were compared with cortical fusion events. In localised
regions of the egg, there is a 6s delay between the detection of calcium release
and fusion of cortical granules. The rate of calcium accumulation was altered
experimentally to ask whether this delay was necessary to achieve a threshold
concentration of calcium to trigger fusion, or was a time-dependent activation of
the cortical granule fusion apparatus after the 'triggering' event. Calcium
release rate was attenuated by blocking inositol 1,4,5-triphospate (InsP3)-gated
channels with heparin. Heparin extended the time necessary to achieve a minimum
concentration of calcium at the sites of cortical granule exocytosis. The data
are consistent with the conclusion that much of the delay observed normally is
necessary to reach threshold concentration of calcium. Cortical granules then
fuse with the plasma membrane. Further, once the minimum threshold calcium
concentration is reached, cortical granule fusion with the plasma membrane occurs
in a pattern suggesting that cortical granules are non-uniform in their calcium
sensitivity threshold.
PMID- 9652073
TI - Nuclear envelope removal/maintenance determines the structural and functional
remodelling of embryonic red blood cell nuclei in activated mouse oocytes.
AB - Nuclei of embryonic red blood cells (e-RBC) from 12-day mouse fetuses are
arrested in G0 phase of the cell cycle and have low transcriptional activity.
These nuclei were transferred with help of polyethylene glycol (PEG)-mediated
fusion to parthenogenetically activated mouse oocytes and heterokaryons were
analysed for nuclear structure and transcriptional activity. If fusion proceeded
25-45 min after oocyte activation, e-RBC nuclei were induced to nuclear envelope
breakdown and partial chromatin condensation, followed by formation of nuclei
structurally identical with pronuclei. These 'pronuclei', similar to egg (female)
pronuclei, remained transcriptionally silent over several hours of in vitro
culture. If fusion was performed 1 h or later (up to 7 h) after activation, the
nuclear envelope of e-RBC nuclei remained intact and nuclear remodelling was less
spectacular (slight chromatin decondensation, formation of nucleolus precursor
bodies). These nuclei, however, reinforced polymerase-II-dependent transcription
within a few hours of in vitro culture. Our present experiments, together with
our previous work, demonstrate that nuclear envelope breakdown/maintenance are
critical events for nuclear remodelling in activated mouse oocytes and that
somatic dormant nuclei can be stimulated to renew transcription at a time when
the female pronucleus remains transcriptionally silent.
PMID- 9652074
TI - The polysulphate binding domain of human proacrosin/acrosin is involved in both
the enzyme activation and spermatozoa-zona pellucida interaction.
AB - Mammalian acrosin is a protease present as a zymogen in the acrosome of a non
reacted mammalian sperm, and in vitro is able to carry out limited hydrolysis of
homologous and heterologous zonae pellucidae. On the other hand, sulphated
polymers and zona pellucida glycoproteins bind to acrosin on a domain different
from the active site, named the polysulphate binding domain (PSBD). Thus it is
believed that acrosome-reacted spermatozoa bind to glycan chains of the zona
pellucida through PSBD participating as secondary binding receptor. The aim of
the present work was to study the role of PSBD during both human gamete
interaction and acrosin activation. In this work we present evidence that the
anti-human acrosin monoclonal antibody C5F10 is directed to an epitope located on
or near the PSBD on human proacrosin/acrosin. Moreover, we show that this
antibody is able to inhibit both proacrosin activation induced by fucoidan and
the sperm binding to the zona pellucida. Our results suggest that the same PSBD
is involved in both sperm secondary binding, during zona pellucida penetration,
and proacrosin activation.
PMID- 9652075
TI - Voltage-gated calcium channels in Pleurodeles oocytes: classification, modulation
and functional roles.
AB - In unfertilised Pleurodeles oocytes, two distinct types of high voltage-activated
Ca2+ channels are expressed: a slowly inactivating Ca2+ channel and a transient
one. The first is dihydropyridine-sensitive and is referred to as the L-type Ca2+
channel. The transient channel is highly sensitive to Ni2+. Phosphorylation
through protein kinases G and A facilitates and inhibits the L-type Ca2+ channel
respectively. The transient type channel is insensitive to stimulation by protein
kinases (A and G). The functional expression of L-type and transient Ca2+
channels is modulated by the two maturation seasons. The transient Ca2+ currents
are only observed during the resting season, while the L-type current is observed
either alone during the breeding season or in association with the transient
current during the resting season. Moreover, the current density of the L-type
Ca2+ channel is much greater during the breeding season than the resting season.
Thus, the wide distribution of L-type Ca2+ channels in Pleurodeles oocytes during
the two seasons suggests that the roles of these channels may be important in the
regulation of the maturation process.
PMID- 9652076
TI - An olfactory neuronal network for vapor recognition in an artificial nose.
AB - Odorant sensitivity and discrimination in the olfactory system appear to involve
extensive neural processing of the primary sensory inputs from the olfactory
epithelium. To test formally the functional consequences of such processing, we
implemented in an artificial chemosensing system a new analytical approach that
is based directly on neural circuits of the vertebrate olfactory system. An array
of fiber-optic chemosensors, constructed with response properties similar to
those of olfactory sensory neurons, provide time-varying inputs to a computer
simulation of the olfactory bulb (OB). The OB simulation produces spatiotemporal
patterns of neuronal firing that vary with vapor type. These patterns are then
recognized by a delay line neural network (DLNN). In the final output of these
two processing steps, vapor identity is encoded by the spatial patterning of
activity across units in the DLNN, and vapor intensity is encoded by response
latency. The OB-DLNN combination thus separates identity and intensity
information into two distinct codes carried by the same output units, enabling
discrimination among organic vapors over a range of input signal intensities. In
addition to providing a well-defined system for investigating olfactory
information processing, this biologically based neuronal network performs better
than standard feed-forward neural networks in discriminating vapors when small
amounts of training data are used.
PMID- 9652077
TI - Reduction of a model for an Onchidium pacemaker neuron.
AB - The eight-variable model for the giant neuron localized in the esophageal ganglia
of the marine pulmonate mollusk Onchidium verruculatum is reduced to four- and
three-dimensional systems by regrouping variables with similar time scales. These
reduced models replicate the complex behavior including beating, periodic
bursting and aperiodic bursting displayed by the original full model when the
parameter Iext representing the intensity of the constant DC current stimulation
is varied across a wide range. The complex behavior of the full model arises from
the interaction of fast and slow dynamics, and depends on the time scale Cs of
the slow dynamics. The four-variable reduced model is constructed independently
from the parameter Cs so that it reproduces the two-dimensional bifurcation
structure of the full model for the two parameters Iext and Cs. The three
variable reduced model is derived for a specific value of Cs. The parameters of
this model are tuned so that its one-parameter bifurcation diagram for Iext
closely matches that of the full model. Correspondence between bifurcation
structures ensures that both reduced models reproduce the various discharge
patterns of the full model. Similarity between the full and reduced models is
also confirmed by comparing mean firing frequencies and membrane potential
waveforms in various regimes. The reduction exposes the factors essential for
reproducing the dynamics of the full model; indeed, it shows that the eight
variables representing the membrane potential and seven gating variables of six
ionic currents in the full model account, in fact, for three basic processes
responsible for excitability, post-discharge refractoriness and slow membrane
modulation.
PMID- 9652078
TI - Cortical memory dynamics.
AB - Biological memories have a number of unique features, including (1) hierarchical,
reciprocally interacting layers, (2) lateral inhibitory interactions within
layers, and (3) Hebbian synaptic modifications. We incorporate these key features
into a mathematical and computational model in which we derive and study Hebbian
learning dynamics and recall dynamics. Introducing the construct of a feasible
memory (a memory that formally responds correctly to a specified collection of
noisy cues that are known in advance), we study stability and convergence of the
two kinds of dynamics by both analytical and computational methods. A
conservation law for memory feasibility under Hebbian dynamics is derived. An
infomax net is one where the synaptic weights resolve the most uncertainty about
a neural input based on knowledge of the output. The infomax notion is described
and is used to grade memories and memory performance. We characterize the recall
dynamics of the most favorable solutions from an infomax perspective. This
characterization includes the dynamical behavior when the net is presented with
external stimuli (noisy cues) and a description of the accuracy of recall. The
observed richness of dynamical behavior, such as its initial state sensitivity,
provides some hints for possible biological parallels to this model.
PMID- 9652079
TI - Detecting multimodality in saccadic reaction time distributions in gap and
overlap tasks.
AB - In many cases the distribution of saccadic reaction times (SRT) deviates
considerably from a unimodal distribution and may often exhibit several peaks. We
present a statistical approach to determining the number and form of the
individual peaks. The overall density of the reaction times fi(t), i = 1...M
obtained in M different experiments with the same subject is described as the sum
of K basis functions xk(t), k = 1...K with different weights and an error term. A
change in the experimental conditions is assumed to cause a change in the
weights, not in the basis functions. We minimize the square of the difference
(measured data minus approximation), divided by the error of the data.
Incrementing K step by step we determine the necessary number of basis functions.
This method is applied to data of six subjects tested in different saccade tasks.
We detect five different modes: two in the range 80-140 ms (express modes), two
in the range 145-190 ms (fast-regular mode) and one at about 230 ms (slow-regular
mode). These modes are located at about the same positions for different
subjects. The method presented here not only proves statistically the existence
of several modes in SRT distributions but also allows the distributions to be
described by a few characteristic numbers that go beyond the mean values and
standard deviations.
PMID- 9652080
TI - Quantization of human motions and learning of accurate movements.
AB - This paper presents a mathematical model for the learning of accurate human arm
movements. Its main features are that the movement is the superposition of smooth
submovements, the intrinsic deviation of arm movements is considered, visual and
kinesthetic feed-back are integrated in the motion control, and the movement
duration and accuracy are optimized with practice. This model is consistent with
the jerky arm movements of infants, and may explain how the adult motion behavior
emerges from the infant behavior. Comparison with measurements of adult movements
shows that the kinematics of accurate movements are well predicted by the model.
PMID- 9652081
TI - Standing sway: iterative estimation of the kinematics and dynamics of the lower
extremities from force-plate measurements.
AB - In this study, a model for the estimation of the dynamics of the lower
extremities in standing sway from force plate data only is presented. A three
dimensional, five-segment, four-joint model of the human body was used to
describe postural standing sway dynamics. Force-plate data of the reactive forces
and centers of pressure were measured bilaterally. By applying the equations of
motion to these data, the transversal trajectory of the center of gravity (CG) of
the body was resolved in the sagittal and coronal planes. An inverse kinematics
algorithm was used to evaluate the kinematics of the body segments. The dynamics
of the segments was then resolved by using the Newton-Euler equations, and the
model's estimated dynamic quantities of the distal segments were compared with
those actually measured. Differences between model and measured dynamics were
calculated and minimized, using an iterative algorithm to re-estimate joint
positioning and anthropometric properties. The above method was tested with a
group of 11 able-bodied subjects, and the results indicated that the relative
errors obtained in the final iteration were of the same order of magnitude as
those reported for closed loop problems involved in direct kinematic measurements
of human gait.
PMID- 9652082
TI - Cyclic AMP oscillations in Dictyostelium discoideum: models and observations.
AB - Oscillations in intra- and extracellular cyclic AMP are believed to underlie
aggregation and morphogenesis in Dictyostelium discoideum. Upon comparing
mathematical models with observations we find that the models are, qualitatively
speaking, quite successful. At the same time many features remain unexplained. A
strong case can be made for cyclic AMP-independent oscillations whose basis
remains to be explored.
PMID- 9652083
TI - Modeling oscillations and waves of cAMP in Dictyostelium discoideum cells.
AB - We examine the theoretical aspects of temporal and spatiotemporal organization in
the cAMP signaling system of Dictyostelium discoideum amoebae which aggregate in
a wavelike manner after starvation, in response to pulses of cAMP emitted with a
periodicity of several minutes by cells behaving as aggregation centers. We first
extend the model based on receptor desensitization, previously proposed by
Martiel and Goldbeter, by incorporating the role of G proteins in signal
transduction. The extended model accounts for observations on the response of the
signaling system to successive step increases in extracellular cAMP. In the
presence of the positive feedback loop in cAMP synthesis, this model generates
sustained oscillations in cAMP and in the fraction of active cAMP receptor,
similar to those obtained in the simpler model where the role of the G proteins
is not taken into account explicitly. We use the latter model to address the
formation of concentric and spiral waves of cAMP in the course of D. discoideum
aggregation. Previous analyses of the model showed that a progressive increase in
the activity of adenylate cyclase and phosphodiesterase can account for the
transitions no relay-relay-oscillations-relay observed in the experiments. We
show that the degree of cellular synchronization on such a developmental path in
parameter space markedly affects the nature of the spatial patterns generated by
the model. These patterns range from concentric waves to a small number of large
spirals, and finally to a large number of smaller spirals, as the degree of
developmental desynchronization between cells increases.
PMID- 9652084
TI - Propagating waves control Dictyostelium discoideum morphogenesis.
AB - The morphogenesis of Dictyostelium results from the coordinated movement of
starving cells to form a multicellular aggregate (mound) which transforms into a
motile slug and finally a fruiting body. Cells differentiate in the mound and
sort out to form an organised pattern in the slug and fruiting body. During
aggregation, cell movement is controlled by propagating waves of the chemo
attractant cAMP. We show that mounds are also organised by propagating waves.
Their geometry changes from target or single armed spirals during aggregation to
multi-armed spiral waves in the mound. Some mounds develop transiently into rings
in which multiple propagating wave fronts can still be seen. We model cell
sorting in the mound stage assuming cell type specific differences in cell
movement speed and excitability. This sorting feeds back on the wave geometry to
generate twisted scroll waves in the slug. Slime mould morphogenesis can be
understood in terms of wave propagation directing chemotactic cell movement.
PMID- 9652085
TI - Traveling waves in yeast extract and in cultures of Dictyostelium discoideum.
AB - Biological self-organization was investigated in a biochemical and a cellular
system: yeast extract and cultures of the slime mold Dictyostelium discoideum. In
both systems traveling reaction-diffusion waves occur in response to oscillatory
reactions. Glycolytic degradation of sugar in a yeast extract leads to the
spontaneous formation of NADH and proton waves. Manipulation of the adenine
nucleotide pool by addition of purified plasma membrane ATPase favors the
formation of both reaction-diffusion waves and phase waves. The results indicate
that the energy charge has an important impact for the dynamics of glycolytic
patterns. When affecting the lower part of glycolysis by pyruvate addition the
frequency of wave generation was increased with concomitant formation of rotating
NADH and proton spirals. During morphogenesis of the cellular system
Dictyostelium discoideum, circular and spiral shaped aggregation patterns of
motile amoeboid cells form in response to traveling cAMP waves. Velocity analysis
of the cell movements reveals that the cAMP waves guide the cells towards the
site of wave initiation along optimized trajectories. The minimization of
aggregation paths is based on a mechanism exploiting general properties of
excitation waves. The resulting aggregation territories are reminiscent of
Voronoi diagrams.
PMID- 9652086
TI - Self-organizing molecular networks.
AB - Strong diffusional mixing and short delivery times typical for micrometer and sub
micrometer reaction volumes lead to a special situation where the turnover times
of individual enzyme molecules become the largest characteristic time scale of
the chemical kinetics. Under these conditions, populations of cross-regulating
allosteric enzymes form molecular networks that exhibit various kinds of self
organized coherent collective dynamics.
PMID- 9652087
TI - Spark-to-wave transition: saltatory transmission of calcium waves in cardiac
myocytes.
AB - Using a modular approach, in which kinetic models of various mechanisms of
calcium handling in cells are fine-tuned to in vivo and in vitro measurements
before combining them into whole-cell models, three distinct modes of
transmission of calcium waves in mature and immature frog eggs have been defined.
Two modes of transmission are found in immature eggs, where the inositol 1,4,5
trisphosphate receptor (IP3R) controls release of calcium from the endoplasmic
reticulum (ER). The first mode corresponds to an excitable physiological state of
the cytoplasm and results in solitary waves that can appear as circular or spiral
waves in two dimensions with the wave speed proportional to the square root of
the diffusion constant of calcium. A second mode occurs when the state of the
cytoplasm is oscillatory and because of the small size of the buffered diffusion
constant for calcium, the wave speed can appear to be weakly dependent on
diffusion. In the mature frog egg, where the sperm-induced Ca2+ fertilization
wave is a propagating front, the cytoplasm appears to be bistable and in this
mode the wave speed is also proportional to the square root of the diffusion
constant. Here we investigate a fourth mode of propagation for cardiac myocytes,
in which calcium release from the sarcoplasmic reticulum (SR) is dominated by
clusters of ryanodine receptors spaced at regular intervals. In myocytes a
stochastically excitable myoplasm leads to the spontaneous production of calcium
'sparks' that under certain conditions can merge into saltatory waves with a
speed proportional to the diffusion constant.
PMID- 9652088
TI - Calcium waves and oscillations driven by an intercellular gradient of inositol
(1,4,5)-trisphosphate.
AB - In response to a local mechanical stimulus, mixed glial cells initially exhibit a
propagating intercellular Ca2+ wave. Subsequently, cells within a zone, at a
specific distance from the stimulated cell, display asynchronous intracellular
Ca2+ oscillations. The experimental hypothesis that the initial Ca2+ wave could
be mediated by the passive diffusion of inositol (1,4,5)-trisphosphate (IP3) from
the stimulated cell has been verified by model simulations. Further simulations
with the same model also show that Ca2+ oscillations can only occur within model
cells when the IP3 concentration is within a specific range. Thus, this passive
diffusion model predicts (a) that the IP3 concentration gradient established in
the cells following mechanical stimulation will initiate Ca2+ oscillations in
cells in a specific zone along this gradient and (b) that different Ca2+
oscillatory patterns will occur within a specified oscillatory zone. Both of
these predictions have been confirmed by experimental data. The failure of
experimentally observed Ca2+ oscillations to approach synchrony or entrain
indicates a low intercellular calcium permeability of about 0.1 micron/s, and
further suggests that Ca2+ does not appear to act as a significant messenger in
the initiation of these intercellular Ca2+ waves or oscillations. In conclusion a
passive diffusion of IP3, but not Ca2+, through gap junctions remains the
preferred hypothesis for the mechanism underlying mechanically-stimulated
intercellular calcium waves and Ca2+ oscillations.
PMID- 9652089
TI - A model of mitochondrial Ca(2+)-induced Ca2+ release simulating the Ca2+
oscillations and spikes generated by mitochondria.
AB - Recent evidence underlines a key role of mitochondrial Ca2+ fluxes in cell Ca2+
signalling. We present here a kinetic model simulating the Ca2+ fluxes generated
by mitochondria during mitochondrial Ca(2+)-induced Ca2+ release (mCICR)
resulting from the operation of the permeability transition pore (PTP). Our model
connects the Ca2+ fluxes through the ruthenium redsensitive Ca2+ uniporter, the
respiration-dependent and passive H+ fluxes, the rate of oxygen consumption, the
movements of weak acids across the mitochondrial membrane, the electrical
transmembrane potential (delta psi), and operation of the PTP. We find that two
factors are crucial to account for the various mCICR profiles that can be
observed experimentally: (i) the dependence of PTP opening and closure on matrix
pH (pHi), and (ii) the relative inhibition of the respiratory rate consecutive to
PTP opening. The resulting model can simulate irreversible Ca2+ efflux from
mitochondria, as well as the genesis of damped or sustained Ca2+ oscillations,
and of single Ca2+ spikes. The model also simulates the main features of mCICR,
i.e. the threshold-dependence of mCICR triggering, and the all-or-nothing nature
of mCICR operation. Our model should appear useful to further mathematically
address the consequences of mCICR on the spatiotemporal organisation of Ca2+
signals, as a 'plug-in' module for the existing models of cell Ca2+ signalling.
PMID- 9652090
TI - Ca2+ wave dispersion and spiral wave entrainment in Xenopus laevis oocytes
overexpressing Ca2+ ATPases.
AB - Complex, spatiotemporal patterns of intracellular Ca2+ release in Xenopus oocytes
can be accounted for by the operation of two fundamental processes: Ca2+ release
from the endoplasmic reticulum (ER) via the inositol 1,4,5-trisphosphate receptor
(IP3R) with its inherent dependency on cytosolic Ca2+, and Ca2+ uptake via Ca2+
ATPases. Overexpression of sarco-endoplasmic reticulum Ca2+ ATPases (SERCAs) in
Xenopus oocytes, increases IP3-induced Ca2+ wave frequency and amplitude [1-3].
This effect can be attributed to an increased removal of cytoplasmic Ca2+ and
more efficient refilling of Ca2+ stores. By overexpressing SERCA isoforms, we
report here that Ca2+ waves exhibit dispersion [4-6]. At wavelengths greater than
60 microns, wave velocity is constant. However, wave velocity and amplitude
progressively decreases at smaller wavelengths. Below gamma approximately 20
microns, Ca2+ waves disperse and fail to propagate. In oocytes exhibiting both
spiral and target patterns of Ca2+ release, spiral waves had higher frequencies
and showed entrainment of the surrounding regions. These properties are
characteristic of a classical excitable medium [4-6].
PMID- 9652091
TI - Role of calcium oscillations in mammalian egg activation: experimental approach.
AB - Biological rhythms are everywhere; the pulsatility of intracellular signals
appears to maximise the cellular processes better than constant signaling. The
aim of this paper is, firstly, to review the cellular mechanisms that modulate
calcium oscillator activity during fertilisation and, secondly, to describe
recent results we have obtained by artificially imposing rhythmical calcium
stimulation on fertilised rabbit eggs during in vitro culture. The key finding in
these experiments is that the egg appears to be sensitive to repetitive
signalling during a period that goes far beyond the time of meiosis reinitiation.
When delivered at the proper rhythm transient signalling can optimise
developmental processes.
PMID- 9652092
TI - Link between fertilization-induced Ca2+ oscillations and relief from metaphase II
arrest in mammalian eggs: a model based on calmodulin-dependent kinase II
activation.
AB - Mammalian eggs are ovulated in metaphase II of meiosis, in a state characterized
by high levels of cyclin B and of active maturation promoting factor (MPF). This
arrest is mediated by an activity referred to as cytostatic factor (CSF) which
prevents the degradation of cyclin. Fertilization triggers a train of Ca2+ spikes
which is responsible for the decrease in activity of both MPF and CSF. The
decline in MPF however much precedes that in CSF. Experimental observations on
mammalian eggs indicate that the kinetics of cell cycle resumption much depends
on the temporal pattern of the repetitive Ca2+ spikes. Here, we propose a
theoretical model which accounts for Ca(2+)-induced relief from metaphase II
arrest in mammalian eggs. The model is based on the fact that Ca2+/calmodulin
kinase II (CaMKII) activation is the primary event leading to inactivation of
both CSF and MPF. To account for experimental observations, it has to be assumed
that CaMKII activation affects the level of the active form of the anaphase
promoting complex (APC), which initiates the degradation of cyclin, through two
pathways characterized by different time scales. Thus, we hypothesize that CaMKII
activation by Ca2+ leads to the transformation of a mediator protein from a form
which stimulates the inactivation of the APC into a form which gradually and
indirectly induces the deactivation of CSF. In consequence, a sufficient number
of Ca2+ spikes first triggers the decrease of MPF, thus allowing the egg to enter
in interphase, and later that of CSF. Finally, when CSF is low and when Ca2+
oscillations have stopped, the level of MPF can increase again, a phenomenon that
would correspond to the first mitosis. This model also accounts for the observed
dependence of the time of entry in interphase (marked by the appearance of the
pronuclei) on the frequency of Ca2+ spikes, as well as for the possible entry in
metaphase III arrest, a pathological state of the egg which results from an
insufficient activation by Ca2+. This study provides some theoretical prediction
as to the time of the first mitosis as a function of the temporal pattern of Ca2+
oscillations.
PMID- 9652093
TI - Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism
for unreplicated DNA.
AB - Alternating phases of DNA synthesis and mitosis, during the first 12 cell
divisions of frog embryos, are driven by autonomous cytoplasmic oscillations of M
phase promoting factor (MPF). Cell-free extracts of frog eggs provide a
convenient preparation for studying the molecular machinery that generates MPF
oscillations and the surveillance mechanism that normally prevents entry into
mitosis until chromosomal DNA is fully replicated. Early experiments suggested
that unreplicated DNA blocks MPF activity by inducing phosphorylation of a
crucial tyrosine residue, but recent evidence implicates a stoichiometric
inhibitor (an MPF binding protein) as the 'braking' agent. Using a realistic
mathematical model of the mitotic control system in frog egg extracts, we suggest
that both tyrosine phosphorylation and a stoichiometric inhibitors are involved
in the block of MPF by unreplicated DNA. Both pathways operate by raising the
cyclin threshold for MPF activation. As a bonus, in the process of analyzing
these experiments, we obtain more direct and reliable estimates of the rate
constants in the model.
PMID- 9652094
TI - Mathematical model of the fission yeast cell cycle with checkpoint controls at
the G1/S, G2/M and metaphase/anaphase transitions.
AB - All events of the fission yeast cell cycle can be orchestrated by fluctuations of
a single cyclin-dependent protein kinase, the Cdc13/Cdc2 heterodimer. The G1/S
transition is controlled by interactions of Cdc13/Cdc2 and its stoichiometric
inhibitor, Rum1. The G2/M transition is regulated by a kinase-phosphatase pair,
Wee1 and Cdc25, which determine the phosphorylation state of the Tyr-15 residue
of Cdc2. The meta/anaphase transition is controlled by interactions between
Cdc13/Cdc2 and the anaphase promoting complex, which labels Cdc13 subunits for
proteolysis. We construct a mathematical model of fission yeast growth and
division that encompasses all three crucial checkpoint controls. By numerical
simulations we show that the model is consistent with a broad selection of cell
cycle mutants, and we predict the phenotypes of several multiple-mutant strains
that have not yet been constructed.
PMID- 9652095
TI - Multiple attractors in immunology: theory and experiment.
AB - This selective survey discusses the relative merits of various modeling
approaches in immunology that exhibit multiple attractors, and also assesses the
ability of the different models to contribute to deeper biological understanding.
The first topic is global anti-idiotypic network models, which, like Hopfield
neural network models, exhibit a large number of steady states that are
identified with memory. It is shown that a 'reverse engineering approach' to T
cell vaccination for autoimmunity, featuring steady states corresponding
respectively to 'normality', 'vaccination' and 'disease', is able to spur new
experiments, in spite of the model's deliberate neglect of almost all biological
detail. Mention is made of several other T-cell models that feature bistability
for Th1 or Th2 dominance, or for activation and unresponsiveness.
PMID- 9652096
TI - Apyrase activity and platelet aggregation inhibitors in the tick Ornithodoros
savignyi (Acari: Argasidae).
AB - Ticks are ectoparasites that cause considerable damage to their hosts while
feeding. The feeding process is facilitated by anti-haemostatic factors present
in the tick saliva. Apyrase (ATP diphosphohydrolase, EC 3.6.1.5) is a platelet
aggregation inhibitor found in most haematophagous organisms studied. The present
study describes the identification and characterization of such an activity in
the tick Ornithodoros savignyi. The enzyme conformed to many properties common to
apyrases. These included a low substrate specificity, dependence on bivalent
metal ions for activity and insensitivity to the classical ATPase inhibitors.
Heat denaturation studies, pH optima and similar effects of inhibitors on the
enzyme's ATP and ADP hydrolysing activitives supported its classification as an
apyrase. Salivary gland extracts inhibited the platelet aggregation induced by
ADP, collagen and thrombin and disaggregated aggregated platelets. The results
suggest the presence of two or more anti-platelet factors present in the salivary
glands of this tick species.
PMID- 9652097
TI - Interstadial and infestation level-dependent variation in the transmission
efficiency of Borrelia burgdorferi from mice to Ixodes ricinus ticks.
AB - The efficiency with which the spirochaete Borrelia burgdorferi sensu stricto was
transmitted from laboratory mice to larval and nymphal Ixodes ricinus ticks was
assessed, using the polymerase chain reaction. The transmission efficiency to
nymphs was significantly greater than to larvae when both fed together on the
same host. Increased tick infestation levels of mice were correlated with
significantly greater engorgement weights and higher B. burgdorferi transmission
coefficients from mice to nymphs. These observations indicate that both the
feeding success of ticks and the transmission coefficients from host to tick may
be influenced by the tick infestation level of an infected host. The infestation
level and the relative numbers of each life stage of the tick are factors which
should be considered in the design of transmission experiments.
PMID- 9652098
TI - Treatment of pica through multiple analyses of its reinforcing functions.
AB - We conducted functional analyses of the pica of 3 participants. The pica of 1
participant appeared to be maintained by automatic reinforcement; that of the
other 2 participants appeared to be multiply controlled by social and automatic
reinforcement. Subsequent preference and treatment analyses were used to identify
stimuli that would complete with the automatic function of pica for the 3
participants. These analyses also identified the specific aspect of oral
stimulation that served as automatic reinforcement for 2 of the participants. In
addition, functional analysis-based treatments were used to address the socially
motivated components of 2 of the participants' pica. Results are discussed in
terms of (a) the importance of using the results of functional analyses to
develop treatments for pica and (b) the advantages of developing indirect
analyses to identify specific sources of reinforcement for automatically
reinforced behavior.
PMID- 9652099
TI - Social interaction skills for children with autism: a script-fading procedure for
beginning readers.
AB - Engaging in spontaneous social exchanges is a central skill deficit of children
with autism, and one that is often difficult to remediate. The 3 boys (ages 4, 4,
and 5 years) who participated in this study had acquired small verbal
repertoires, but typically spoke only when answering questions or requesting
preferred edible items or toys, and did not converse with a familiar teacher
during baseline. During teaching, textual cues ("Look" and "Watch me") were
embedded in the youngsters' photographic activity schedules; after learning to
use the scripts, the children's verbal elaborations and unscripted interactions
increased and were maintained when a new recipient of interaction was introduced.
After scripts were faded, unscripted interactions not only continued but also
generalized to different activities that had not been the topic of teaching. The
script-fading procedure enabled children with autism to converse with adults, to
benefit from adults' language models, and to engage in language practice that
contributes to fluency.
PMID- 9652100
TI - Using a self-control training procedure to increase appropriate behavior.
AB - The present study evaluated a technique for teaching self-control and increasing
desirable behaviors among adults with developmental disabilities. Results showed
that when participants were initially given the choice between an immediate
smaller reinforcer and a larger delayed reinforcer, all participants repeatedly
chose the smaller reinforcer. Concurrent fixed-duration/progressive-duration
reinforcement schedules then were introduced in which initially both the smaller
and larger reinforcers were available immediately. Thereafter, progressively
increasing delays were introduced for the schedule associated with the larger
reinforcer only. When initial short-duration requirements for access to the
larger reinforcer were gradually increased, participants repeatedly selected the
larger reinforcer, thereby demonstrating increased self-control.
PMID- 9652101
TI - Effectiveness of functional communication training with and without extinction
and punishment: a summary of 21 inpatient cases.
AB - Functional communication training (FCT) is a frequently used treatment for
reducing problem behavior exhibited by individuals with developmental
disabilities. Once the operant function of problem behavior is identified by a
functional analysis, the client is taught to emit an appropriate communicative
response to obtain the reinforcer that is responsible for behavioral maintenance.
Studies on FCT have typically used small numbers of participants, have reported
primarily on clients for whom FCT was successful, and have varied with respect to
their use of other treatment components. The main purposes of the present study
were to evaluate the efficacy of FCT for treating severe problem behavior in a
relatively large sample of individuals with mental retardation (N = 21) and to
determine the contribution of extinction and punishment components to FCT
treatment packages. FCT with extinction was effective in reducing problem
behavior for the majority of clients and resulted in at least a 90% reduction in
problem behavior in nearly half the applications. However, when demand or delay
to-reinforcement fading was added to FCT with extinction, treatment efficacy was
reduced in about one half of the applications. FCT with punishment (both with and
without fading) resulted in at least a 90% reduction in problem behavior for
every case in which it was applied.
PMID- 9652102
TI - Visual identity matching and auditory-visual matching: a procedural note.
AB - After preliminary computerized training on visual-visual identity matching, a 5
year-old boy with autism (Sam) was given visual-visual and auditory-visual
matching-to-sample tests with new stimuli. He did well in matching dictated name
samples to 20 pictures, 26 printed upper case letters, and 9 single-digit
numbers. In matching the visual stimuli (pictures, letters, or numbers) to
themselves, however, he did not perform well. We then increased the number of
picture comparisons per trial from two to three. In tests after this three
comparison training, Sam correctly matched on 95% of the original 20-stimulus,
four-comparison, identity-matching test trials. He went on to demonstrate
accurate identity matching of the numbers, letters, and new pictures. In identity
matching tests on the table top, he performed poorly until the stimulus array was
made to resemble the stimulus arrangement on the computer. These findings showed
that seemingly small procedural changes can influence performance and
demonstrated that successful auditory-visual matching does not guarantee
proficiency in visual-visual identity matching.
PMID- 9652103
TI - Identifying work preferences among individuals with severe multiple disabilities
prior to beginning supported work.
AB - We evaluated a prework assessment for predicting work-task preferences among
workers with severe multiple disabilities prior to beginning supported work. The
assessment involved comparing worker selections from pairs of work tasks drawn
from their future job duties. Results of workers' choices once they began their
jobs in a publishing company indicated that the assessment predicted tasks that
the workers preferred to work on during their job routines. Results are discussed
regarding other possible means of determining preferred types of supported work.
PMID- 9652104
TI - Increasing compliance with medical procedures: application of the high
probability request procedure to a toddler.
AB - The effects of high-probability (high-p) requests on compliance with low
probability (low-p) responses have received increased attention from applied
investigators. This study examined the effects of a high-p procedure on a
toddler's compliance with medical procedures. Compliance to low-p requests
occurred more frequently following compliance to high-p requests, suggesting that
this procedure may be useful across different topographies of compliance.
PMID- 9652105
TI - A behavioral intervention for improving verbal behaviors of heroin addicts in a
treatment clinic.
AB - Positively reinforcing appropriate behaviors improved verbal behaviors of opioid
dependent patients in a buprenorphine treatment clinic. During B phases of an
ABAB design, clients received stickers for engaging in appropriate verbal or
nonverbal behaviors. Each sticker provided a chance of winning $25. No
reinforcement was provided during the A phases. Appropriate verbal behaviors
increased during reinforcement periods, and inappropriate verbal behaviors
decreased.
PMID- 9652106
TI - Simplified habit reversal treatment for chronic hair pulling in three
adolescents: a clinical replication with direct observation.
AB - Three developmentally normal adolescents with chronic hair pulling were treated
with a simplified habit reversal procedure consisting of awareness training,
competing response training, and social support. Treatment resulted in an
immediate reduction to near-zero levels of hair pulling, with one to three
booster sessions required to maintain these levels. The results were maintained
from 18 to 27 weeks posttreatment, although 1 participant reported difficulty at
follow-up. The effectiveness of simplified habit reversal and suggestions for
future research are discussed.
PMID- 9652107
TI - Effects of immediate self-correction, delayed self-correction, and no correction
on the acquisition and maintenance of multiplication facts by a fourth-grade
student with learning disabilities.
AB - This study compared the effects of immediate self-correction, delayed self
correction, and no correction on the acquisition and maintenance of
multiplication facts by a fourth-grade student with learning disabilities. Data
from daily and maintenance tests indicated that both correct response rate and
accuracy were higher when self-correction was immediate rather than delayed or
absent.
PMID- 9652108
TI - Effects of wrist weights on self-injurious and adaptive behaviors.
AB - The effects of wrist weights on the self-injurious and adaptive behaviors of a
young boy with profound mental retardation were evaluated. Application of wrist
weights reduced SIB by 92% and was associated with either increases or stable
levels of multiple novel and preexisting adaptive behaviors.
PMID- 9652109
TI - Protein phosphorylation: technologies for the identification of phosphoamino
acids.
AB - Protein phosphorylation plays a central role in many biological and biomedical
phenomena. In this review, while a brief overview of the occurrence and function
of protein phosphorylation is given, the primary focus is on studies related to
the detection and analysis of phosphorylation both in vivo and in vitro. We focus
on phosphorylation of serine, threonine and tyrosine, the most commonly
phosphorylated amino acids in eukaryotes. Technologies such as radiolabelling,
antibody recognition, chromatographic methods (HPLC, TLC), electrophoresis, Edman
sequencing and mass spectrometry are reviewed. We consider the speed, simplicity
and sensitivity of tools for detection and identification of protein
phosphorylation, as well as quantitation and site characterisation. The
limitations of currently available methods are summarised.
PMID- 9652110
TI - Protein binding on polyelectrolyte-treated glass. Effect of structure of adsorbed
polyelectrolyte.
AB - Polyelectrolyte adsorption can be used to modify the surface of chromatographic
packings in order to make them more suitable for protein separations. We studied
the binding of proteins to controlled pore glass (CPG) on which the polycation
poly(diallyldimethylammonium chloride) (PDADMAC) was noncovalently immobilized
through electrostatic interaction. We found that the selectivity of PDADMAC for
bovine serum albumin vs. beta-lactoglobulin, identified in previous selective
coacervation studies, is conserved after its immobilization on the CPG surface.
Protein binding results showed that the pH, ionic strength, and mixing time for
polyelectrolyte adsorption all affect subsequent protein binding, presumably via
the molecular properties of the adsorbed polyelectrolyte layer. The
polyelectrolyte adsorption layer thickness, for polyelectrolyte adsorbed at pH
9.0, ionic strength I = 0.001, was measured with size-exclusion chromatography as
delta H = 2.5 +/- 0.5 nm. Quasielastic light scattering measurement of the
polyelectrolyte hydrodynamic layer thickness (HLT) with a model system of PDADMAC
and silica, supported a correlation between the structure of the adsorbed
polyelectrolyte layer (e.g., loops and tails) and subsequent protein binding,
although differences in magnitude between delta H and HLT suggest that adsorption
onto silica may not mimic adsorption on CPG.
PMID- 9652111
TI - Toroidal coil counter-current chromatography. Achievement of high resolution by
optimizing flow-rate, rotation speed, sample volume and tube length.
AB - This paper deals with optimization of a new seal-free compact toroidal coil
centrifuge to achieve high resolution in analytical counter-current
chromatography (CCC). Toroidal coil CCC (hydrostatic motion) has advantages
compared with high-speed CCC (efficiently mixing solution with planetary motion)
in the separation of protein or easily emulsified samples. A toroidal coil
separation column of 0.4 mm I.D. PTFE tubing was accommodated around the
periphery of the cylindrical centrifuge bowl. Using a two-phase solvent system
composed of chloroform-acetic acid-0.1 M hydrochloric acid (2:2:1, v/v/v) and a
set of dinitrophenyl-amino acids as test samples, a series of experiments was
performed with parameters such as the column length, sample volume, flow-rate,
elution mode of the mobile phase and rotation speed. The highest efficiency, over
10,000 theoretical plates, was achieved with a 100 m long coiled tube and an 11
ml total capacity at a flow-rate of 0.01 ml/min at 800 rpm.
PMID- 9652112
TI - Calculation of peptide retention coefficients in normal-phase liquid
chromatography.
AB - The retention of 121 peptides was studied on a TSK Amide-80 column using
solutions containing 0.1% trifluoroacetic acid and an increasing linear gradient
of water in acetonitrile. The contribution of each residue to retention was
calculated by linear multiple regression analysis. This paper described the
contribution values 'hydrophilicity retention coefficients'. The result is an
index of hydrophilicity retention coefficients for normal-phase liquid
chromatography, analogous to the hydrophobicity indices calculated for the
reversed-phase liquid chromatography. The order of residues in the index of one
mode was substantially the inverse of the others'. Using the new hydrophilicity
retention coefficients, retention times could be predicted for peptides of known
amino acid content and sequence.
PMID- 9652113
TI - Retention behavior of D,L-dansyl-amino acids on a human serum albumin chiral
stationary phase: effect of a mobile phase modifier.
AB - The effect of perchlorate anion as a mobile phase modifier on the retention of
dansyl norvaline and dansyl tryptophan enantiomers on a human serum albumin (HSA)
column was studied by varying the chaotropic agent concentrations. The
thermodynamic parameters for the transfer of a solute from the mobile to the HSA
stationary phases were determined from linear van't Hoff plots. An enthalpy
entropy compensation study revealed that the type of interaction between the
solute and HSA was independent of the molecular structure. The parabolic
variations observed with the enthalpic and entropic terms of dansyl amino acid
transfer in relation to the concentration of perchlorate anion were considered to
be the result of the change from reversed to normal-phase conditions for this
chromatographic system.
PMID- 9652114
TI - Rapid verification of disulfide linkages in recombinant human growth hormone by
tandem column tryptic mapping.
AB - An automated tryptic mapping method was developed for characterization of
disulfide linkages in recombinant human growth hormone (rhGH). The hormone was
trypsin digested and the peptide fragments concentrated by eluting rhGH through
an immobilized trypsin column and transferring the peptides directly to a
reversed-phase liquid chromatography (RP-LC) column where they were collected.
Reaction time was controlled by the flow-rate. Following tryptic digestion of a
sample, the immobilized enzyme column was uncoupled from the flow train by a
switching valve and the RP-LC column eluted with a solvent gradient ranging from
0.1% trifluoroacetic acid (TFA) with 1% acetonitrile (ACN) to ACN with 0.1% TFA
and 5% water. This two-step mapping process was achieved within 2 h on both
native and reduced rhGH samples. The chromatographic elution position and mass
spectra matrix-assisted laser desorption ionization time-of-flight mass
spectrometry of native rhGH and sulfur-containing peptides were determined with
standards. Standards of the individual sulfhydryl (-SH) containing peptides and
all possible disulfide linked peptides that could result from coupling the -SH
peptides in disulfide linkages were obtained by synthesis and chromatographic
purification. This approach allowed the chromatographic elution position of all
possible mismatched disulfide containing peptides to be established and samples
of rhGH to be examined for improper folding.
PMID- 9652115
TI - Hybrid affinity chromatography of alpha-galactosidase from Verbascum thapsus L.
AB - Purification of alpha-galactosidase from the roots of Verbascum thapsus L. was
difficult to achieve using conventional methods due to the presence of coloured
contaminants. A newly developed procedure, hybrid affinity chromatography, which
was based on a mixed matrix separation procedure, using a substrate analogue and
an immobilized metal affinity matrix as ligands, respectively, allowed the
purification of this enzyme with good recovery. The method should be applicable
to other proteins as well.
PMID- 9652116
TI - Preparative ion-exchange chromatography of proteins from dairy whey.
AB - A preparative-scale ion-exchange chromatographic process is described for the
separation of the four major proteins and lactose from sweet dairy whey.
Experiments using a commercial anion-exchange resin were carried out to determine
the optimum conditions for initially separating the proteins alpha-lactalbumin,
beta-lactoglobulin, bovine serum albumin, immunoglobulin G and lactose from a
sweet dairy whey mixture. The separation was accomplished with simultaneous step
elution changes in salt concentration and pH. It was found that the anion
exchange step was most effective in separating beta-lactoglobulin from the feed
mixture. Following the anion-exchange separation, its breakthrough curve was
processed using a commercial cation-exchange resin to further recover the
valuable immunoglobulin G. The whey output from an east Tennessee cheese
manufacturer was used as a feedstream for the preparative scale experiments and
as a reference in scaling to an economically optimized production level
operation.
PMID- 9652117
TI - High-performance liquid chromatography of Pasteurella haemolytica leukotoxin
using anion-exchange perfusion columns.
AB - An exotoxin, called leukotoxin (LKT), from Pasteurella haemolytica, which had
previously proved difficult to purify, was purified by high-performance liquid
chromatography using rigid highly hydrophilic microparticulate anion-exchange
columns. These anion-exchange stationary phases were employed to overcome
difficulties of the relatively hydrophobic LKT interacting with dextran or
styrene-based resins. While a short non-porous DEAE column allowed the partial
microscale purification of the leukotoxin at pH 7.0, a high capacity strong anion
exchange column of the perfusion chromatography type permitted the purification
of LKT on a much larger scale. The purification of the LKT on the large pore
strong anion-exchange perfusion column was best achieved when three consecutive
linear gradients at increasing NaCl concentration in 20 mM Tris buffer, pH 8.0,
containing 6.0 M urea and 0.25% Tween 20 were used. Under these conditions, a
better separation was obtained for the tetrameric and aggregate peaks of LKT from
the early eluting contaminant peaks. This separation scheme allowed good recovery
of activity and purification of the LKT to near homogeneity.
PMID- 9652118
TI - On-line preconcentration and determination of chromium(VI) in waters by high
performance liquid chromatography using precolumn complexation with 1,5
diphenylcarbazide.
AB - A method for on-line chromatographic preconcentration and determination of
chromium(VI) traces has been developed. Chromate was preconcentrated on a C18
column (50 x 6 mm I.D.) after complexation with diphenylcarbazide (DPC).
Following the preconcentration step, analysis of the sample was performed using a
C18 column (100 x 6 mm I.D.) with an eluent containing 6.10(-3) mol/l sulphuric
acid and 20% (v/v) acetonitrile. Direct spectrophotometric detection at 546 nm
was used. Experimental parameters such as mobile phase pH, DPC concentration,
preconcentration flow-rate, sample volume were optimized for preconcentration and
detection of Cr(VI)-DPC complex. Under the optimum conditions, most metal ions
[Cr(III), Fe(III), Cu(II), Hg(II), Mo(VI), V(V)] and inorganic anions did not
interfere. A detection limit of 0.02 ng/ml Cr(VI) can be attained when a sample
volume of 100 ml is used. The technique has been applied successfully to the
determination of Cr(VI) traces in drinking, surface and groundwater samples and
the recoveries of added chromium were in the range 94-104%.
PMID- 9652119
TI - Headspace solid-phase microextraction analysis of volatile sulphides and
disulphides in wine aroma.
AB - Sulphur compounds (S-compounds) are important constituents of wine off-flavours.
Headspace solid-phase microextraction (HS-SPME) combined with gas chromatography
coupled to flame photometric detection (GC-FPD) was used to develop a suitable
method to analyse volatile sulphides and disulphides. This is a very simple and
fast technique which gives good reproducibility at microgram/l levels (relative
standard deviations < 10%). The analytes were extracted from the headspace of the
samples by using either polydimethylsiloxane or polyacrylate coated fused-silica
fibers in an SPME unit. Then, the fiber was inserted into the injector of a gas
chromatograph and the extracted S-compounds were thermally desorbed. The
influence of different parameters, such as ionic strength, stirring, headspace
volume, ethanol concentration, time and temperature of extraction, was studied.
The extraction of the fibers varies considerably for the different sulphur
compounds studied. The most volatile compounds were the least extracted by the
coating fibers tested. The standard additions technique, applied to real samples,
gave the recoveries > 94%. The detection limits range between 3 micrograms/l and
50 ng/l. The overall process was successfully applied to identify and quantify S
compounds in white and red wines.
PMID- 9652120
TI - Capillary zone electrophoresis with indirect UV detection of haloacetic acids in
water.
AB - A capillary zone electrophoresis (CZE) system for determining haloacetic acids in
water was optimized with indirect photometric detection. Two different carrier
electrolytes, potassium hydrogenphthalate and sodium 2,6
naphthalenedicarboxylate, were evaluated in terms of sensitivity and two
different electroosmotic flow modifiers, tetradecyltrimethylammonium bromide and
hexadecyltrimethylammonium bromide, were tested. Parameters such as electrolyte
concentration and pH, and the concentration of the electroosmotic flow modifiers,
which affect the CZE separations, were investigated. The method was used to
determine haloacetic acids in chlorine tap water using the liquid-liquid
extraction process.
PMID- 9652121
TI - Separation of ergot alkaloids and their epimers and determination in sclerotia by
capillary electrophoresis.
AB - Capillary electrophoresis has been shown to be a very useful analysis technique
for secondary metabolites of plants. In the present study a method is described
for the qualitative and quantitative determination of ergot alkaloids and their
epimers. The extraction from the biological matrix yields recoveries of 50-97%,
depending on the individual alkaloid. Using a mixture of 20 mM beta-cyclodextrin
(CD), 8 mM gamma-CD, 2 M urea and 0.3% (w/w) poly(vinyl alcohol) to phosphate
buffer at pH 2.5 the simultaneous separation of all analytes was achieved. A 37
cm (30 cm) fused-silica capillary, at a voltage of 25 kV and a temperature of 20
degrees C, was used for the analysis. Overall analysis time for the separation
was 12 min. The limit of detection of the alkaloids using UV detection at 214 nm
can be improved 30-fold to about 9.10(-8) M when laser-induced fluorescence
detection is applied.
PMID- 9652122
TI - The manumycin-group metabolites.
PMID- 9652123
TI - Steroids: reactions and partial synthesis.
PMID- 9652124
TI - Biosynthesis of fatty acids and related metabolites.
PMID- 9652125
TI - Following the invisible trail: kinematic analysis of mate-tracking in the copepod
Temora longicornis.
AB - We have analysed the fine-scale kinematics of movement of male and female
copepods, Temora longicornis, to resolve how these small animals find their
mates. Location of the trail initially involves rapid random turning and high
rates of directional change. Males subsequently increase their rate of movement
as they follow the trail, and execute a regular pattern of counter turns in both
x,z and y,z planes to stay near or within the central axis of the odour field.
Pursuit behaviour of males is strongly associated with female swimming behaviour,
suggesting that quantifiable variations in the structure of the odour signal
released by females affects male tracking. The behavioural components of mate
tracking in Temora are very similar to those of other animals that employ
chemically mediated orientation in their search for mates and food, and we
conclude that male Temora find their mates using chemoperception. The kinematic
analysis indicates both sequential and simultaneous taxis mechanisms are used by
Temora to follow the odour signal. This, in turn, indicates that rather than
responding to a diffuse plume, males are following a signal more accurately
characterized as a chemical trail, and copepods appear to use mechanisms that are
similar to those employed by trail-following terrestrial insects such as ants.
While Temora expresses similar behaviours to those of a variety of chemosensory
organisms, the ability to track a three-dimensional odour trail appears unique,
and possibly depends on the persistence of fluid-borne odour signals created in
low Reynolds number hydrodynamic regimes.
PMID- 9652126
TI - The fluid physics of signal perception by mate-tracking copepods.
AB - Within laboratory-induced swarms of the marine copepod Temora longicornis, the
male exhibits chemically mediated trail-following behaviour, concluding with
fluid mechanical provocation of the mate-capture response. The location and
structure of the invisible trail were determined by examining the specific
behaviour of the female copepods creating the signal, the response of the male to
her signal, and the fluid physics of signal persistence. Using the distance of
the mate-tracking male from the ageing trail of the female, we estimated that the
molecular diffusion coefficient of the putative pheromonal stimulant was 2.7 x
10(-5) cm2 s-1, or 1000 times slower than the diffusion of momentum. Estimates of
signal strength levels, using calculations of diffusive properties of odour
trails and attenuation rates of fluid mechanical signals, were compared to the
physiological and behavioural threshold detection levels. Males find trails
because of strong across-plume chemical gradients; males sometimes go the wrong
way because of weak along-plume gradients; males lose the trail when the female
hops because of signal dilution; and mate-capture behaviour is elicited by
suprathreshold flow signals. The male is stimulated by the female odour to
accelerate along the trail to catch up with her, and the boundary layer
separating the signal from the chemosensitive receptors along the copepod
antennule thins. Diffusion times, and hence reaction times, shorten and
behavioural orientation responses can proceed more quickly. While 'perceptive'
distance to the odour signal in the trail or the fluid mechanical signal from the
female remains within 1-2 body lengths (< 5 mm), the 'reactive' distance between
males and females was an order of magnitude larger. Therefore, when nearest
neighbour distances are 5 cm or less, as in swarms of 10(4) copepods m-3, mating
events are facilitated. The strong similarity in the structure of mating trails
and vortex tubes (isotropic, millimetre-centimetre scale, 10:1 aspect ratio, 10s
persistence), indicates that these trails are constrained by the same physical
forces that influence water motion in a low Reynolds number fluid regime, where
viscosity limits forces to the molecular scale. The exploratory reaches of mating
trails appear inscribed within Kolmogorov eddies and may represent a measure of
eddy size. Biologically formed mating trails, however, are distinct in their flow
velocity and chemical composition from common small-scale turbulent features; and
mechanoreceptive and chemoreceptive copepods use their senses to discriminate
these differences. Zooplankton are not aimless wanderers in a featureless
environment. Their ambit is replete with clues that guide them in their efforts
for survival in the ocean.
PMID- 9652127
TI - Mercury in water and sediments of the southern Baltic sea.
AB - Total mercury concentrations [HgT] were measured in samples of water and
sediments collected from the southern Baltic Sea from the period 1993-1995.
Picomolar concentrations of HgT were found in offshore surface water. Higher
levels were measured in samples from the plum of the Vistula. An exceptionally
high concentration of mercury (25 pM HgT, 5 pM methylmercury) was measured in the
near bottom, quasi-anoxic water of the Gdansk Deep and explained by the release
of mercury from fine grained sediments covering the bottom. In the sediments, the
largest contents of HgT were found in fine grained, organic rich deposits of the
Baltic deeps. The increase in mercury contents in the upper layers of sediments
deposited within the last 100-150 years was attributed to the anthropogenic load
of mercury and its increased scavenging to sediments with organic matter.
PMID- 9652128
TI - Mercury distribution in relation to iron and manganese in the waters of the St.
Lawrence river.
AB - Waters entering the St. Lawrence River from Lake Ontario and from the Ottawa
River have been sampled on a quaternary basis between March 1995 and October
1996. Mercury, iron, manganese, organic carbon and other chemical parameters have
been determined in the filtered water (< 0.5 micron) and suspended particles (>
0.5 micron). Average total mercury concentrations (+/- standard deviation, number
of determinations) in filtered samples were 1.3 +/- 0.9 pM (39) at the mouth of
Lake Ontario and 4.0 +/- 2.3 pM (54) at the outlet of the Ottawa River. The
respective average concentrations in suspended particles were 1.1 +/- 0.4 (39)
and 0.6 +/- 0.2 (55) nmol g-1. Partial correlation analyses reveal that in the
fraction < 0.5 micron--which seems to consist of a significant fraction of
colloids--mercury was significantly linked to iron, while in the particulate
phase, mercury was related to manganese. Mercury was not correlated with organic
carbon. A sorption model on iron and manganese hydroxides is proposed to explain
these observations.
PMID- 9652129
TI - An examination of spatial variation in mercury concentrations in otter (Lutra
canadensis) in south-central Ontario.
AB - Hair samples were collected from otter (Lutra canadensis) trapped in several
parts of south-central Ontario, Canada. The concentrations of total Hg in hair
were compared with methyl mercury concentrations in liver tissues from the same
individuals to determine if hair is a suitable monitoring tissue. Hg in the two
tissues was significantly correlated. Hair was used to monitor Hg in 51
individuals from four townships. The concentrations of total Hg in hair ranged
from 4 to 20 micrograms/g. No significant variation among the four sample regions
existed. Generally the highest concentrations were found in the youngest members
of the population. Some possible explanations for the observations are presented.
PMID- 9652130
TI - Permanent impairment in the feeding behavior of grayling (Thymallus thymallus)
exposed to methylmercury during embryogenesis.
AB - Embryos of grayling (Thymallus thymallus) were exposed to different
concentrations of methylmercury (0.16, 0.8, 4.0 and 20 micrograms Hg l-1) during
the first 10 days of development. The exposure resulted in body concentrations in
the newly hatched fry of 0.09, 0.27, 0.63 and 3.80 micrograms Hg g-1 wet wt.,
respectively. A control group had a body concentration of 0.01 microgram Hg g-1.
Morphological disturbances were only found in the highest exposure group. Three
years later, at a size of 13.8 +/- 0.8 cm, the different groups were tested for
sublethal toxicant effects on foraging behavior. In the first series of
experiments we tested the foraging efficiency of the fish when kept alone for 5
min in small flow-through aquariums. In the second series of experiments we
tested the competitive ability of eight individuals from an exposed group vs.
eight individuals from a control group when kept together for 30 min in a 300-1
aquarium. In both experiments live Dapnia magna were used as prey. We found
impaired feeding efficiencies and reduced competitive abilities in grayling from
the exposed groups which as yolk-fry had Hg concentrations of 0.27 microgram g-1
or more. In the foraging efficiency experiments these groups were 15-24% less
efficient as compared to the control group. In the competitive ability
experiments the control group caught two to six times as many preys as these
exposed groups. Such harmful body concentrations of Hg (> 0.27 microgram g-1) may
be found in eggs from piscivorous fishes in lakes receiving diffuse atmospheric
depositions of mercury. We suggest such concentrations may have ecological
consequences by reducing the fitness of the affected populations.
PMID- 9652131
TI - Mercury in alligators (Alligator mississippiensis) in the southeastern United
States.
AB - Mercury methylation may be enhanced in wetlands and humic-rich, blackwater
systems that crocodiles and alligators typically inhabit. Given their high
trophic level and long life-spans, crocodilians could accumulate significant
burdens of Hg. Our objectives were to survey Hg concentrations in alligators from
several areas in the southeastern United States to test their utility as
sentinels of Hg contamination, to examine relationships among Hg concentrations
in various tissues and to look for any differences in tissue Hg concentrations
among locations. We measured total Hg concentrations in alligators collected in
the Florida Everglades (n = 18), the Okefenokee National Wildlife Refuge, Georgia
(n = 9), the Savannah River Site (SRS), South Carolina (n = 49) and various
locations in central Florida (n = 21), sampling tissues including blood, brain,
liver, kidney, muscle, bone, fat, spleen, claws and dermal scutes. Alligators
from the Everglades were mostly juvenile, but Hg concentrations in tissues were
high (means: liver 41.0, kidney 36.4, muscle 5.6 mg Hg/kg dry wt.).
Concentrations in alligators from other locations in Florida were lower (means:
liver 14.6, kidney 12.6, muscle 1.8 mg Hg/kg dry wt.), although they tended to be
larger adults. Alligators from the Okefenokee were smallest and had the lowest Hg
concentrations (means: liver 4.3, kidney 4.8, muscle 0.8 mg Hg/kg dry wt.). SRS
alligators had the greatest size range and intermediate Hg levels (means: liver
14.9, muscle 4.8 mg Hg/kg dry wt.). At some locations, alligator length was
correlated with Hg concentrations in some internal organs. However, at three of
the four locations, muscle Hg was not related to length. Tissue Hg concentrations
were correlated at most locations however, claw or dermal scute Hg explained less
than 74% of the variation of Hg in muscle or organs, suggesting readily-obtained
tissues, such as scutes or claws, have limited value for non-destructive
screening of Hg in alligator populations.
PMID- 9652132
TI - Mercury in a widely consumed fish Micropogonias furnieri (Demarest, 1823) from
four main Brazilian estuaries.
AB - We analyzed mercury levels in the white muscular tissue of a fish (Micropogonias
furnieri) originated from four Brazilian estuaries during the period between the
summer 1990 and spring 1991. Mercury levels were below the maximum permissible
limit established for food by the Brazilian legislation (500.0 ng.g-1 wet wt.).
The measured mercury concentrations ranged from 17.4 to 266.0 ng.g-1 (wet wt.),
for Guanabara Bay 19.5-252.2 ng.g-1 (wet wt.), for Sepetiba Bay 23.0-433.7 ng.g-1
(wet wt.), for Ilha Grande Bay 13.8-296.3 ng.g-1 (wet wt.) for Conceicao Lagoon.
Positive relationships were observed between mercury concentration in fish and
the length and weight of the fishes. Weight normalized concentration showed
Guanabara Bay presented the higher levels and the Conceicao Lagoon presented the
lowest levels. Ilha Grande Bay presented the second highest levels after Sepetiba
Bay, although the former is considered a non-contaminated area.
PMID- 9652133
TI - Development of fish mercury concentrations in Finnish reservoirs from 1979 to
1994.
AB - Mercury (Hg) concentrations in burbot (Lota lota), perch (Perca fluviatilis),
northern pike (Esox lucius), roach (Rutilus rutilus), whitefish (Coregonus
lavaretus) and peled (C. peled) were monitored in 18 reservoirs situated in
western and northern Finland over a period of 16 years (1979-1994). The
reservoirs were impounded from 1964 to 1980. The surface areas ranged between 1
and 417 km2. Data from downstream sites and reference lakes were compared to
reservoir mercury data. Generally, fish Hg concentrations in reservoirs exceeded
those in natural lakes. Shortly after inundation, fish mercury concentrations
clearly increased and remain 15-25 years above background concentrations. The
mean Hg concentrations in standardized 1 kg pike from 1989 to 1993 was 0.45 mg/kg
in natural lakes and 0.58 mg/kg in reservoirs. The 1 mg/kg fish Hg level
recommended by health authorities as the upper limit for human consumption was
still exceeded in two reservoirs 20 years old or more. The two largest reservoirs
(24 and 27 years old in 1994) with significant commercial fishing had Hg levels
below 0.5 mg/kg in all fish species studied. Statistical models for predicting
the Hg concentrations in the weight standardized pike were verified with the
observed data. For most of the reservoirs, predictions from models based on pH,
organic matter (COD) in water, the extent of water level regulation and reservoir
age agreed well with observed data. In the most southern, new (under 20 years
old) and heavily regulated reservoirs, pike Hg concentration followed a
logarithmic function of reservoir age. Model predictions of mercury in pike in
the planned Vuotos reservoir (in northern Finland) predicted that Hg would exceed
1 mg/kg Hg for the first 12 years after the flooding.
PMID- 9652135
TI - The development of bioengineered skin.
AB - Driven by the need for donor tissue for patients suffering from extensive burns,
alternatives to autologous and cadaver-derived tissue have been under development
for the past 20 years. Unilayered and bilayered models representing the skin's
epidermal and/or dermal components have been developed using both cells and
matrix materials. In addition to their use in patients with extensive burns,
trials using these products on refractory and challenging patients with both
acute and chronic wounds have led to the commercial availability of some of these
products.
PMID- 9652134
TI - The Trimera mouse: generating human monoclonal antibodies and an animal model for
human diseases.
AB - Monoclonal antibodies of human origin may have great therapeutic value in the
treatment of cancer, autoimmune disorders and viral or bacterial infections.
Several methods for generating human monoclonal antibodies exist; some are based
on the transplantation of a functioning human immune system into severe combined
immunodeficient (scid) mice or into Trimera mice, which are mice that have been
lethally irradiated and radioprotected by transplantation of bone-marrow cells
from scid mice. Trimera mice could be also used to develop animal models for
human diseases by transplanting infected human tissue fragments and for creating
models for cell therapy.
PMID- 9652136
TI - Current trends in 'artificial-nose' technology.
AB - Basic principles derived from biological olfaction, such as combining
semiselective sensor arrays with pattern recognition, have been used to develop
instrumentation capable of broad-band chemical detection and quantification.
Commercially available instruments are useful in areas including quality control
in the food, beverage and fragrance industries, environmental monitoring,
chemical-purity and -mixture analysis, and medical diagnostics. Ongoing research
is aimed at the development of more-advanced instruments that are smaller,
cheaper, faster and more stable and reliable. These second-generation instruments
are likely to find an increasing number of applications, including the on-line
monitoring of fermentation and other bioprocesses.
PMID- 9652137
TI - Hybrid enzymes: manipulating enzyme design.
AB - Hybrid enzymes are engineered to contain elements of two or more enzymes. Hybrid
enzyme approaches, by taking advantage of the vast array of enzymatic properties
that nature has evolved, as well as the strategies that nature has used to evolve
them, are becoming an increasingly important avenue for obtaining novel enzymes
with desired activities and properties.
PMID- 9652139
TI - Perfluorochemicals: their applications and benefits to cell culture.
AB - The properties of perfluorochemical liquids, particularly their high gas
solubility, enables them to be exploited in cell biotechnology. They can
facilitate respiratory-gas delivery to prokaryotic and eukaryotic cells in
culture; in some systems, they can stimulate production of biomass, yields of
commercially important cellular products and, for plant systems, expression of
totipotency. The recoverability, and hence recycleability, of perfluorochemicals
from aqueous systems makes their routine use a commercially feasible option. This
article reviews the applications and beneficial effects of perfluorochemicals in
cultured microbial, animal and plant cells, including both aerobic and anaerobic
systems.
PMID- 9652138
TI - Using molecular techniques to identify new microbial biocatalysts.
AB - Evolution has favoured microorganisms that produce efficient enzymes with
substrate-adapted biocatalytic activities. Progress in molecular techniques,
especially expression cloning, molecular screening, protein engineering and in
vivo and in vitro shuffling, have paved the way for greater speed and accuracy in
cloning enzyme genes from microorganisms and generating versions with improved
properties. Recently, two new approaches have been added: screening directly from
uncultivated microorganisms and generating additional hits by database mining
using bioinformatic tools.
PMID- 9652140
TI - A sparsely vascularised zone in the cortex of the bovine ovary.
AB - We consider that the microvascular bed may play a role in the initiation and
maintenance of growth from primordial to primary follicles. Therefore, using
immunochemistry, we examined microvessels in calf and cow ovaries to identify the
presence of factor VIII-related antigen endothelial cells. A vessel-poor zone was
observed in the cortex of immature and mature cow ovaries. Primordial and primary
follicles were assembled in this zone. It is concluded that follicular dormancy
is likely to be maintained by the scarcity of microvessels and thus by the
consequent poverty of the blood supply.
PMID- 9652142
TI - Occurrence and importance of glomus organs (Hoyer-Grosser's organs) in the skin
of the equine and bovine mammary gland.
AB - Glomus organs (Hoyer-Grosser's organs) were frequently found in the corium and
the subcutis of the skin of the equine and bovine mammary gland. They were most
frequently situated in the border zone between the stratum profundum and the
stratum superficiale corii. These specialized vascular structures (arterio-venous
anastomosis) were present in all investigated skin areas. Although the glomus
organs varied in size and shape, they possessed common histologic structures: an
arteriole entered the connective capsule of the glomus and divided into strongly
convoluted arterio-venous channels; the arteriovenous channels united in the end
to form a venule; the mentioned vascular elements were covered by a connective
capsule and were thus united to an organ-like structure. Questions concerning
their occurrence, their functional interpretation, their relevance, the size of
the glomus organs as well as the possible involvement of the lymphatics were
discussed.
PMID- 9652141
TI - Histochemistry of complex carbohydrate in the major salivary glands of hoary
bamboo rats (Rhizomys purinosus).
AB - The major salivary glands (parotid glands, monostomatic sublingual glands and
submandibular glands) were obtained from hoary bamboo rats (Rhizomys purinosus)
and fixed in Bouin's solution. Paraffin sections were subjected to a battery of
staining methods including lectin staining for demonstration of complex
carbohydrates. Among the three major salivary glands, unique histochemical
features were observed in the submandibular gland. Different from most myomorpha
species, submandibular glands of the hoary bamboo rats have two types of
secretory cells in the secretory endpieces. One type of cells showed positive
reactions with Alcian blue (AB)(pH2.5), periodic acid-Schiff (PAS) and some
lectins (peanuts agglutinin, Griffonia simplicifolia I, Maclura pomifera
agglutinin). The granular ducts, which exist in animals belonging to suborder
myomorpha, were not observed in the submandibular glands of this animal.
PMID- 9652143
TI - Chemoreceptive epithelioid cells in the chicken aorta. An electron microscopical
study.
AB - Aggregations of granulated epithelioid cells exist in the chicken aorta. In the
present study, the locational characteristics of the epithelioid cells were
investigated via an electron microscopic approach. Epithelioid cells were found
mainly in two regions; the tunica interna just below the endothelial cell layers,
and the intermediate region of the tunica media. In the former, the epithelioid
cells were in contact with endothelial cells and sometimes directly exposed to
the aortic lumen. No contact between the epithelioid cells and the nerve endings
was observed in this region. On the other hand, in the intermediate region of the
tunica media, five or more epithelioid cells were aggregated, and the synaptic
structures were occasionally observed. Additionally, the epithelioid cells in
this region was observed to closely contact smooth muscle cells. In an experiment
using horseradish peroxidase injection, reactions were detected in the
intercellular spaces between the epithelioid cells and endothelial cells. These
results suggest that the epithelioid cells localized in the subendothelial region
receive information from the aortic lumen, whereas their aggregations in the
tunica media are controlled by the nervous system.
PMID- 9652144
TI - [Anatomic characteristics pf the elbow joint of the cheetah (Acinonyx jubatus)].
AB - Anatomical structures of elbow joints of six cheetahs were examined by
dissection, corrosion casts and radiography. As a result, it was observed that
the distal end of humerus is divided into the trochlea humeri for articulation
with the ulna and the capitulum humeri for articulation with the radius. As the
trochlea humeri is posed oblique and looks like a disc-shaped cone sector,
flexion. Flexion of elbow joint is always combined with adduction of the distal
parts of the limb, and, respectively, extension with abduction. The cylindrical
but also in sagittal direction convex capitulum humeri enables the head of the
radius all movements on a spheric sector. Furthermore, advantageous preconditions
for rotation in the proximal radioulnar joint are the mighty medical coronoid
process, the displacement of the radial tuberosity to the caudal surface of the
radius and the insertion of the biceps brachii muscle exclusively on this
elevation of the radius. Limiting factors are the insertions of collateral
ligaments at the antebrachial skeleton. The lateral collateral ligament inserts
only on the radius, the medial collateral ligament mainly on the ulna. The radial
anular ligament directly connects the two coronoid processes of the ulna and
moreover is intracapsular. The joint capsule is common for both the cubital and
the proximal radioulnar joint and five pouches could be described. These were
between the lateral epicondyle of humerus and the olecranon, underneath the
tendon of origin of the extensor carpi ulnaris muscle, cranially in the bend of
the elbow joint, between the head of the radius and the tendon of origin of
supinator muscle and the lateral part of radial anular ligament, just as between
the medial epicondyle of humerus and the tendons of origin of flexor muscles of
the forearm.
PMID- 9652145
TI - Morphological and immunohistochemical considerations on the basal ganglia in
pigeon (Columba livia).
AB - Morphological and immunohistochemical studies carried out particularly around the
level of the basal ganglia (BG) in birds, are reported and commented on. Our
results showed, on paraffin embedded avian BG, both the histological features and
the immunohistochemical findings on immunofluorescence distribution of some
neuropeptides (especially Metenkephalin) in the striatal complex. By comparing
our results of Metenkephalin immunoreactivity (Menkir) with the referred
analogous ones of Substance P (SP) quoted in literature, we confirmed the
strikingly similar labelling at the levels of the Lobus paraolfactorius (LPO) and
Paleostriatum augmentatum (PA), in contrast with the very low immunoreactivity at
the Paleostriatum primitivum (PP) levels. We were able also to demonstrate the
strong MEnk-ir of the neurons of the Nucleus accumbens, Nucleus septalis and
paraventricularis. All these findings are also in accord to the interpretation by
many AA (Wynne and Gunturkun, 1995; Reinez et al., 1983), about the anatomical
correspondence between the LPO-PA complex of birds and the caudate-putamen in
mammals. Some MEnk + 'wooly like fibres' described in our specimens in the PA (on
the contrary reported in the Gpe segment of mammals) apparently escape these
correspondence.
PMID- 9652146
TI - An immunohistochemical study of bovine palatine and pharyngeal tonsils at 21, 60
and 300 days of age.
AB - An immunohistochemical study was performed on three groups of young cattle (21,
60 and 300 days of age). Tonsils (palatine and pharyngeal) and mucosae (nasal and
oral) were removed. Eight monoclonal antibodies (specific for CD3, CD2, CD4, CD8,
WC1, cell-surface IgM, cell-surface IgG and MHC class II molecules) and an
avidin/biotin complex method on frozen sections were used. The immunological
cytoarchitecture of bovine tonsils is similar to that of human tonsils.
Nevertheless, these lymphoid tissues are not fully developed during the first
weeks of life: T and B dependent areas not well-differentiated, few germinal
centres, few intra-epithelial WC1+ T lymphocytes. In contrast, at 2 months,
tonsils possess all the elements of a mucosa-associated lymphoid tissue (MALT).
Tonsillar or mucosal epithelium is infiltrated by a large number of CD8+, WC1+ T
lymphocytes and cells which express MHC class II molecules. Between 21 and 60
days, the number of WC1+ T lymphocytes increase markedly in the tonsillar
epithelium. These results accredit the hypothesis that the presence of antigens
has an effect on the localization of these lymphocytes at these sites.
PMID- 9652148
TI - Studies on the parietal region of the cervid skull. III. On the occurrence of an
interparietal in Cervus.
AB - The occurrence of an os interparietal was studied in two transparent preparations
of fetal red deer (Cervus elaphus) heads and in 14 dried skulls of fetal to early
postnatal individuals from four Cervus species (C. elaphus, C. nippon, C.
duvauceli and C. eldi). In 14 of the 16 specimens, an interparietal was present
as either a paired or single bone. In only a neonate red deer and a 5-week-old
sika deer this skull element was missing. We therefore conclude that an os
interparietal, developing from paired centres of ossification, is normally
present in Cervus species. This clearly distinguishes them from the fallow deer,
where an interparietal is missing (Kierdorf and Kierdorf, 1992b). Our findings
thus support the view that the fallow deer should be considered a distinct genus
Dama instead of being included within Cervus.
PMID- 9652147
TI - Immunohistochemical study of normal and mange (S. scabiei var. rupicaprae)
infested chamois (Rupicapra rupicapra L.) skin.
AB - The immunohistochemical study of chamois (Rupicapra rupicapra L.) skin showed
that a limited number of available monoclonal and polyclonal antibodies expressed
reactivity with skin cell components. These included cytokeratins, vimentin,
desmin, neuron-specific enolase and S-100 protein with almost the same
distribution pattern as already described in the skin of humans and animals.
Antibodies used for labelling skin-associated lymphoid tissues and other cells
with the immunologic function in human skin failed to demonstrate these cells in
the chamois skin with the exception of LCA and OKT6 antibodies. Epidermal
Langerhans cells were reliably demonstrated only by the enzyme histochemical
method for adenosine triphosphatase, while the majority of mononuclear cells in
dermal infiltrates showed a strong immunoreaction with OKT6 antibody. The
histologic and histochemical analysis showed that the dermal infiltrations in
infested skin consisted of macrophages, lymphocytes, granulocytes, mastocytes and
fibroblasts. The chamois skin affected with sarcoptes mange showed a significant
loss of cytokeratins in the epidermis and its derivatives. Particular
keratinocytes showing nonspecific staining with several antibodies were also
described and discussed in this paper.
PMID- 9652149
TI - Distention of the lateral intercellular spaces (LIS) in the proximal tubule cells
of the non-stenosed kidney of the 2K-1C Goldblatt model of hypertension as
evidence of pressure diuresis.
AB - This study shows the development of two major deformities in the non-stenosed
kidney of the 2K-1C Goldblatt model; namely the widening of the LIS and the
enlargement of the basilar interdigitations of the proximal tubule cells. These
deformities were much less in the 2K-1C animals treated with the angiotensin I
converting enzyme inhibitor (AICEI) cilazapril. From these findings it is
suggested that the non-stenosed kidney is operating under the diuretic effect of
the elevated systemic blood pressure (SBP) via an increase in the renal
interstitial hydrostatic pressure (RIHP). Therefore, the AII antidiuretic effect
is masked by the diuretic effect of the elevated SBP. The suggested rise in urine
output fits well with the idea that kidneys lose water and sodium when SBP
increases enormously. Therefore, in this model of hypertension, the non-stenosed
kidney tries to lower SBP by losing water and sodium, an excretion behavior which
is opposite to that of the stenosed kidney. Thus, the rise in SBP in this model
is probably due to an increase in the vascular peripheral resistance rather than
fluid accumulation.
PMID- 9652150
TI - Regional peripheral vascular supply based on the superficial temporal artery in
dogs and cats.
AB - Cutaneous arterial blood supply to the temporal region was evaluated in 8 dogs
and 8 cats. Subtraction radiography and angiography of the carotid and
superficial temporal arteries were used in 4 dogs and 4 cats to determine
arterial blood supply to the temporal region and frontalis muscle. A myocutaneous
axial pattern flap based on the superficial temporal artery and frontalis muscle
may be indicated for cosmetic reconstruction in dogs and cats following surgical
resection of neoplastic lesions or traumatic wounds in the maxillofacial region.
The frontalis muscle was identified as the thin subcutaneous continuation of the
platysma muscle extending cranially and rostrally. Dissection of the temporal
region in 4 dogs and 4 cats revealed the subcutaneous location of the superficial
temporal artery as it continues rostrally from the caudal aspect of the zygomatic
arch.
PMID- 9652151
TI - Immunohistochemical demonstration of cytoskeletal proteins in the testis of the
Japanese black bear, Ursus thibetanus japonicus.
AB - The seasonal changes of the cytoskeletal protein expressions were
immunohistochemically investigated in the testes of Japanese black bear, Ursus
thibetanus japonicus. A strong immunoreaction for alpha-smooth muscle actin is
restricted to the vascular smooth muscle cells and the peritubular cells which
surround the seminiferous tubules by several layers throughout the year. Weak
immunoreactions for B4 antigen and desmin were observed in the vascular smooth
muscle cells and in a part of peritubular cells throughout the year. A strong
immunoreaction for vimentin was also detected in the fibroblasts and Leydig
cells, in addition to the vascular smooth muscle and epithelial cells and the
peritubular cells throughout the year. A strong alpha-tubulin immunoreaction was
detected in the elongating spermatids during the acrosome phase of spermiogenesis
in May and June. The cytoplasm of several Sertoli cells was faintly immunoreacted
for vimentin in the basal and lateral region, while an intense alpha-tubulin
reaction was seen in the entire cytoplasm in May, April and June. In November,
January and March, the immunoreactions for vimentin and alpha-tubulin strongly
accumulate in a perinuclear region of Sertoli cells when developmental spermatids
are not seen in the seminiferous tubules. These accumulations in the
immunoreactions for vimentin and alpha-tubulin seem to be caused by the reduction
in size of Sertoli cells cytoplasm with season. However, the seasonal changes of
distributions in the cytoskeletal proteins are obscure in the bear testes. These
results suggest that the contents of cytoskeletal proteins may not change in
relation to the morphological differences with season in the testes of the
seasonal breeders.
PMID- 9652152
TI - Births, marriages, divorces, and deaths for November 1997.
PMID- 9652153
TI - Biocompatible dialysis membranes: do they matter?
PMID- 9652154
TI - Overview of dialyzer elution studies: impact on current views on
bioincompatibility and future perspectives.
PMID- 9652155
TI - Haemodialysis-related bioincompatibility: fundamental aspects and clinical
relevance.
PMID- 9652156
TI - The newly developed sulfonylurea glimepiride: a new ingredient, an old recipe.
AB - Disturbances in insulin secretion and insulin action are both involved in the
pathophysiology of type 2 (or non-insulin-dependent) diabetes mellitus. The newly
developed sulfonylurea (SU) derivative glimepiride has a marked insulin secretory
effect both in vitro and in vivo, and is capable of increasing plasma insulin
levels with approximately 50% in type 2 diabetes subjects. Glimepiride improves
metabolic control comparable but not superior to other (second generation) SU
derivatives. Although it has been advocated for once-daily use, maximum effect is
presumably achieved by twice-daily dosing. One of the most important side-effects
of SU remains hypoglycemia in some patients, which may last for several hours.
Although there is some indication that the use of glimepiride leads to fewer
hypoglycemic episodes than glibenclamide, the differences reported sofar are not
statistically significant.
PMID- 9652157
TI - Jaundice associated with acenocoumarol exposure.
AB - A 69-year-old man developed cholestatic liver enzyme disturbances three and a
half weeks after starting treatment with acenocoumarol because of a deep venous
thrombosis in his leg. Serological testing showed no signs of recent viral
infections. A presumptive diagnosis of hepatotoxicity caused by the use of
acenocoumarol was made and the anticoagulant was replaced by low molecular weight
heparin. Three weeks after withdrawal of the acenocoumarol, the enzymes had
improved. The patient made a full recovery within two months. This case suggests
a causal relationship between acenocoumarol exposure and liver damage.
PMID- 9652158
TI - A patient with acquired haemophilia A and pemphigus.
AB - Haemophilia A is usually a genetic deficiency of coagulation factor VIII (F
VIII). The development of antibodies against F VIII is a well known and frequent
complication in the treatment of haemophilia A. Rarely, a F VIII inhibitor arises
spontaneously, causing a condition which is known as acquired haemophilia A. We
describe a patient with acquired haemophilia A and pemphigus, who presented with
spontaneous haematomas of the extremities. Laboratory tests showed an activated
partial thromboplastin time (aPTT) of 71 s (normal: 26-36 s), a F VIII
concentration of 9% (normal: 60-140%), and a F VIII inhibitor-activity of 7.5
Bethesda Units/ml (B.U./ml, normal: 0). The haematomas disappeared within a few
days and the laboratory tests normalized within 6 weeks, after administration of
a booster of oral corticosteroids. One and a half years after the corticosteroids
were stopped, both the clinical and the laboratory course of the patient has been
uneventful. As far as we know, the combination of acquired haemophilia A and
pemphigus has been reported in the literature only three times before. The
diagnosis acquired haemophilia A should be considered in a patient presenting
with a newly arisen haemorrhagic diathesis.
PMID- 9652159
TI - Primary oligoarthritis in a parent of a child with meningococcal group B sepsis
and meningitis.
AB - The mother of an eight-month-old child with meningitis presented with petechiae
on her trunk and lower extremities, fever, and oligoarthritis. Although pathogens
were never revealed by Gram stain nor cultured from the aspirated joint fluid,
the diagnosis was primary meningococcal arthritis. This diagnosis was based on
the simultaneous occurrence of Neisseria meningitidis group B infection in her
son and the clinical presentation.
PMID- 9652160
TI - [The P-pill debate. From media circus to critical risk evaluation].
PMID- 9652161
TI - [P-pills and thrombosis].
AB - This review provides an account of the present situation as reflected by findings
in recent studies, which illustrate epidemiological, clinical and metabolic
aspects of thrombosis associated with oral contraceptive (OC) usage. With the
reduction of the oestrogen content of OCs, the relative risk for acute myocardial
or cerebral thrombosis is now 1.5-3. Low-dose OCs containing third generation
gestagens seem to be associated with less risk of infarction, and possibly of
cerebral thrombosis, than are OCs containing second generation gestagens. The
risk of venous thrombosis is increased 2-4-fold in conjunction with the usage of
low-dose OCs with second generation gestagens, and possibly slightly more (3-5
fold) in conjunction with OCs containing third generation gestagens, though this
is of small clinical significance. When prescribing OCs for women at an increased
risk of venous thrombosis, a low-dose pill with a second generation progestagen
seems to be preferable. If OCs are prescribed to women at an increased risk of
arterial thrombosis, OCs with third generation progestagens seem to be a
reasonable first choice. Women with no thrombotic predisposion can safely use
any type of low-dose OCs [corrected].
PMID- 9652162
TI - [For some it is a matter of necessity. Worry about the overuse of an
antidepressant].
PMID- 9652163
TI - [How soon will we have artificial blood?].
AB - The development of red cell substitute oxygen-carriers has reached a stage where
stroma-free haemoglobin solutions (SFHSs) and perfluorocarbon-based substitutes
are undergoing clinical trials. However, there is no evidence to suggest that
such products will become available, other than for restricted, well-defined
indications. Where SFHSs are concerned, the supply of haemoglobin, the strictly
limited shelf-life, and the short intravascular half-life are the most important
problems to be solved, whereas the use of perfluorocarbons is limited, in
particular due to the need of positive pressure ventilation to maintain high
oxygen tension. Red cell substitutes for general use will remain a dream in the
foreseeable future. Measures to enhance blood preservation and to promote the
optimal use of blood products will be the most important areas of transfusion
research in the immediate future.
PMID- 9652164
TI - [Malrotation--a rare cause of recurrent abdominal pain in children].
PMID- 9652165
TI - [Patient readmission. Medical diagnosis and risk factors of emergency readmission
within 14 days].
AB - Every tenth patient discharged from a medical department at a general hospital in
Sweden during the period, 1992-1994, required emergency re-admission within 14
days. The risk of re-admission appeared to be unrelated to the duration of
hospitalisation before discharge or to the occupancy rate. However, a high risk
of emergency re-admission was found to be associated with four diagnoses: acute
myocardial infarction, angina pectoris, heart failure and chronic obstructive
lung disease. Plans are under way to launch a multicentre intervention study of
emergency re-admission to departments of medicine.
PMID- 9652166
TI - [Causes of death and incidence of cancer in physicians and lawyers in Iceland].
AB - A retrospective study is accomplished in Iceland to study whether mortality and
cancer incidence among male physicians (1,210) were lower than those among men of
the general population and lawyers (1,032). Overall mortality among lawyers was
similar to that of the general male population, however, mortality among the
physicians was lower than that of the general population and the lawyers, due to
lower mortality for all cancers (SMR 0.73), cerebrovascular diseases (SMR 0.53)
and respiratory diseases (SMR 0.54). The physicians had higher mortality for
suicide committed by drugs, solid or liquid substances. Cancer was not as
frequent among the physicians as among the lawyers, particularly for lung cancer,
the SIR was 0.45, but the rates were higher for cancer of the colon and brain
among the physicians than among others.
PMID- 9652167
TI - [The merit profile--an instrument for the evaluation of academic achievement].
AB - The concept of a merit profile has been evolved at Karolinska Institute in
Stockholm, whereby not only research achievements but also teaching,
administrative and clinical skills and experience are each given merit ratings to
produce an individual profile. This approach is based on the notion that all of
these fields of activity constitute integregal facets of a scat of higher
learning in medicine, and that a candidate's relative merits in each of these
areas should be seen not only in relation to the overall academic goals but also
to practical, professional considerations. The merit profile is intended to be
used in selection for appointments and promotion, and as a basis for the
continued enhancement of individual competence, and salary review.
PMID- 9652169
TI - Long-term vs. short-term journal impact: does it matter?
PMID- 9652168
TI - Citation statistics for the individual journals of The American Journal of
Physiology.
PMID- 9652170
TI - Structure and function of molybdopterin containing enzymes.
AB - Molybdopterin containing enzymes are present in a wide range of living systems
and have been known for several decades. However, only in the past two years have
the first crystal structures been reported for this type of enzyme. This has
represented a major breakthrough in this field. The enzymes share common
structural features, but reveal different polypeptide folding topologies. In this
review we give an account of the related spectroscopic information and the
crystallographic results, with emphasis on structure-function studies.
PMID- 9652171
TI - Self-organization in biology and development.
PMID- 9652172
TI - The intrinsic viscosity of biological macromolecules. Progress in measurement,
interpretation and application to structure in dilute solution.
PMID- 9652173
TI - Chloride channels in the sarcoplasmic reticulum of muscle.
PMID- 9652174
TI - AIDS and education: have we done enough?
PMID- 9652175
TI - Liver transplantation in chronic hepatitis B--a new era?
PMID- 9652176
TI - Liver transplant in Singapore--coming of age.
AB - BACKGROUND/AIM OF STUDY: Liver transplantation was first performed in 1967, and
has become an accepted form of treatment worldwide for chronic liver diseases,
acute liver failure and certain metabolic diseases. We document our experience in
Singapore over the last 7 years since the first transplant was performed in 1990.
METHOD: Retrospective study at National University Hospital, Singapore. RESULTS:
Twenty-two operations (10 paediatric and 12 adults) have been performed with the
last 17 having been performed in the last 17 months. Currently, there are 15
survivors (68%) since 1990, and percentage survival is even better if one
considers the cases from the last 17 months when the majority of cases (17
transplants-77%) were performed (77% survival). The most common indication for
transplant was biliary atresia for the paediatric group, while the adults were
transplanted for hepatitis B and C cirrhosis, primary biliary cirrhosis, and
fulminant liver failure. Tacrolimus is the main immunosuppression (10 patients),
with the remaining 5 patients on cyclosporine. Various surgical techniques
(living donor, graft reduction) have been employed successfully to provide a
complete transplant service. Hospital and ICU stays are within normal limits and
the hospital charges range from a low of S$30,000 to S$141,000. CONCLUSION: Liver
transplantation has become a reality in Singapore with outcomes comparable to
other transplant centres. The shortage of donors remains the greatest stumbling
block for further expansion.
PMID- 9652177
TI - A needs assessment and proposal for HIV education among human resource managers
in Singapore.
AB - AIM OF STUDY: To assess the educational needs of human resource managers in
Singapore with regard to the management of HIV at the workplace. No such study
has been described before in an Asian country. METHOD: A self-administered
questionnaire was mailed to all companies (with more than 100 employees) of a
local employers federation (n = 368). RESULTS: A response rate of 64.1% was
achieved. Respondents' knowledge about HIV transmission was found to be good.
However, their attitudes and practices towards infected workers were unfavourable
on such issues as pre-employment screening, medical coverage and termination of
employment. Possible reasons for this disparity include inadequate information
specific to workplace needs, multiple determinants of attitudes (other than
knowledge) and various environmental factors. CONCLUSION: Strategies for an
educational intervention are proposed to facilitate the development of a rational
HIV management policy by local managers.
PMID- 9652178
TI - Distribution patterns of inflammatory sinonasal diseases.
AB - BACKGROUND/AIM OF STUDY: There has been an increase in the demand for coronal
sinus CT scan since the introduction of functional endoscopic sinus surgery; as
the information provided by the scans assist the surgeon in the pre-operative
plannings. Babbel and colleagues had demonstrated five distinctive patterns of
recurring inflammatory sinonasal disease on CT scan. The aim of this study was to
evaluate the patterns in the local population and to see if there was a
difference compared to the Caucasian population. METHODS AND MATERIALS: A
retrospective review of 302 scans done between March 1993 and September 1995 was
carried out. All scans were carried out using a 5 mm thickness to cover the
posterior sinuses and a 3 mm thickness to cover the anterior sinuses. The scans
were then grouped into the various patterns and an analysis was carried out
comparing the differences in the patterns between the Chinese and the non
Chinese, and between the local population and the Caucasian population in
Babbel's series. RESULTS: There was no significant difference between the Chinese
and the non-Chinese in the distribution of the various disease patterns. When
compared to the Caucasian population, the local population had more sinonasal
polyposis and sphenoethmoidal recess obstruction. CONCLUSION: The smaller nasal
passages of the Asians, particularly in the Chinese, could be the reason for the
more prevalence of Type III and Type IV disease compared to the Caucasian
population. The more constant and frequent exposure to allergens might also
contribute to the increased prevalence of Type IV disease.
PMID- 9652179
TI - Transcatheter closure of patent ductus arteriosus using detachable spring coils.
AB - OBJECTIVE: To report our experience with transcatheter PDA closure using
detachable spring coils. METHODS: Suitable patients who presented between March
1996 to July 1997 were selected for coil occlusion of PDA after the diagnosis is
confirmed on colour doppler echocardiography. Twenty-seven patients underwent an
attempt at transcatheter closure of PDA with coils. Twenty-one were native ducts
while 6 were residual ductal leaks following surgical ligation (4) and Rashkind
umbrella occlusion (2). RESULTS: The patients' age ranged from 20 months to 39
years (median 5.5 years) and weighed from 10.5 kg to 49 kg (median 21 kg). The
PDA diameter ranged from 1.3 mm to 5 mm (mean 2.4 mm). Twenty-four patients had
coils successfully deployed (one coil in each patient) and all had PDA diameter
of < or = 3.5 mm. Seventeen had complete occlusion on echocardiographic colour
doppler assessment within 24 hrs. Follow-up colour doppler assessment showed
complete occlusion in all 24 patients by 6 months. There were no cases of coil
embolisation or any other complications. Unsuccessful coil deployment was
encountered in 3 patients with PDA diameter of > or = 4 mm. CONCLUSION: The
detachable coil system allows for complete control over coil release and
therefore deployment is precise and complications are minimised. Transcatheter
closure of PDA with the detachable coil is a safe and effective method especially
for small ducts (< or = 3.5 mm).
PMID- 9652180
TI - Down syndrome screening in Singapore--the effectiveness of a second trimester
serum screening policy modelled on 29,360 pregnancies in KK Women's and
Children's Hospital.
AB - AIM OF STUDY: To assess the effectiveness of a proposed second trimester Down
syndrome serum screening policy in Singapore. METHOD: Auditing the effectiveness
of an age-only policy and comparing it against a serum screening policy modelled
on the same maternal population of KK Women's and Children's Hospital in 1994 and
1995. RESULTS: KK Women's and Children's Hospital's (KKH) maternal age
distribution is similar to the national age distribution of mothers. Sixteen
percent (16.7%) of mothers in KKH, in 1994 and 1995, were 35 years or older at
delivery. Based on our hospital birth defect registry, 66% (35/53) of Down
Syndrome pregnancies occurred in mothers who were 35 years or older at delivery
and 43% (23/53) in the oldest 6.5% of mothers (38 years or older at delivery).
Using various models on KKH's population structure to estimate the expected
number of Down Syndrome livebirths expected, 52%-55% and 34%-36% of Down Syndrome
livebirths were expected to occur in the oldest 16.7% and 6.5% of mothers
respectively. These simulated figures are much lower than the figures from the
data and needs further study, assuming that the Western Down Syndrome risk model
to be applicable to our population. The overall uptake of amniocentesis
irrespective of gestational age at booking was 28%. In mothers who were 35 years
or older at delivery and booked before 22 weeks gestation, the uptake rate of
amniocentesis was 49%. There was a substantial difference in the uptake rate when
the counselling was done by trained counsellers compared to those who were not.
CONCLUSION: We would expect that for a fixed amniocentesis rate of 6.5% and
16.7%, serum screening would be able to detect 71% and 85% respectively of the
Down syndrome pregnancies. This is more efficient than figures published from
Western populations as our patients are older.
PMID- 9652181
TI - L-asparaginase induced intracranial haemorrhage in acute lymphoblastic leukemia.
AB - A 20-year-old national serviceman with acute lymphoblastic leukaemia, developed a
large left parieto-occipital haemorrhage 7 days after completion of induction
chemotherapy. Severe hypofibrinogenemia had been noted while he was receiving L
asparaginase. The haemorrhage could not be attributed to thrombocytopenia,
disseminated intravascular coagulopathy, arterio-venous malformation, berry
aneurysm or leukaemic infiltration because each of these causes was carefully
investigated into and excluded. We conclude that the intracranial haemorrhage was
likely L-asparaginase induced, an uncommon but recognised complication associated
with L-asparaginase therapy.
PMID- 9652182
TI - Surgical reconstruction for mesenteric angina in a patient with infra-renal
aortic occlusive disease--a case report and review.
AB - Mesenteric angina is an uncommon condition which is underdiagnosed, or diagnosed
too late when the patient has a mesenteric infarct. The preferred treatment is by
surgical reconstruction. A case presented here illustrates the condition and the
modifications necessary to reconstruct a completely occluded lower abdominal
aorta in treating both mesenteric angina and claudication.
PMID- 9652183
TI - A review of the role of stroke units in the modern day management of stroke-
implications for stroke care in Singapore.
AB - Among the strategies to combat stroke, an important cause of mortality and
morbidity in Singapore, is the establishment of stroke units. Stroke units are
characterised by a geographical co-location of stroke patients or care by a
mobile multidisciplinary stroke team of specialists; the provision of 24-hour CT
scanning, laboratory, monitoring, neurology and neuroradiology services, and
availability of neurosurgical and angiography services is recommended. Stroke
intensive care units are expensive to run and do not reduce mortality-however,
they may have a role for the aggressive management of carefully selected
patients. Non-intensive stroke and rehabilitation units have been shown to reduce
mortality, morbidity, institutionalisation, and even length of stay and
healthcare costs. They facilitate better utilisation of resources, audit,
teaching and clinical research. As the number of stroke patients in Singapore is
expected to rise, with minor reorganisation, all Singapore hospitals should be
able to establish their own stroke units.
PMID- 9652184
TI - Acute hepatitis in an asthmatic patient.
PMID- 9652185
TI - Diagnostic difficulties associated with phaeochromocytoma.
PMID- 9652186
TI - Asthma therapy for the 21st century.
PMID- 9652187
TI - On the presence of a putative fourth beta-adrenoceptor in human adipose tissue.
PMID- 9652188
TI - An orange a day keeps the scurvy away.
PMID- 9652189
TI - Fibroblast models of neurological disorders: fluorescence measurement studies.
AB - Biochemical studies of human fibroblasts from patients with neurological
disorders have revealed a wealth of information on how such disorders occur. In
this review, Gerald Connolly describes how recently developed fluorescence video
imaging techniques have been used to study the physiology of skin fibroblasts
isolated from patients with certain neurological disorders, including those
produced by Alzheimer's disease, Lesch-Nyhan syndrome, mitochondrial disorders,
amyotrophic lateral sclerosis and lysosomal disorders. The results of these
studies indicate disruptions in cell homeostasis, particularly specific changes
in Ca2+ homeostasis and autofluorescence, which mirror changes thought to occur
in the CNS of neurologically impaired patients. More extensive studies of these
'systemic changes' using new fluorescent indicators, combined with advances in
imaging techniques, are predicted to increase the potential usefulness of human
skin fibroblasts as experimental models and to help diagnose and treat
neurological disorders.
PMID- 9652190
TI - Therapeutic potential of histamine H3 receptor agonists and antagonists.
AB - The histamine H3 receptor was discovered 15 years ago, and many potent and
selective H3 receptor agonists and antagonists have since been developed.
Currently, much attention is being focused on the therapeutic potential of H3
receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and
Henk Timmerman describe the available H3 receptor agonists and antagonists and
their effects in a variety of pharmacological models in vitro and in vivo. The
possible therapeutic applications of the various compounds are discussed.
PMID- 9652192
TI - Your life in your hands. A surgeon's view of hand function--art expression and
form.
PMID- 9652191
TI - Adenosine A3 receptors: novel ligands and paradoxical effects.
AB - The physiological role of the adenosine A3 receptor is being investigated using
newly synthesized, selective ligands. Recently, in addition to agonists,
selective antagonists have been developed that belong to three distinct, non
purine chemical classes: flavonoids, 1,4-dihydropyridine derivatives (e.g.
MRS1191, which is 1300-fold selective for human adenosine A3 vs A1/A2A receptors,
with a Ki value of 31 nM) and the triazoloquinazolines (e.g. MRS1220, which has a
Ki value of 0.65 nM). The A3 receptor has proven enigmatic in terms of antagonist
ligand specificity, coupling to second messengers, and biological effects in the
CNS, inflammatory system and cardiovascular system. A3 receptors are also
potentially involved in apoptosis. It appears that intense, acute activation of
A3 receptors acts as a lethal input to cells, while low concentrations of A3
receptor agonists protect against apoptosis. Here, Kenneth Jacobson describes how
A3 receptor agonists might be useful in treating inflammatory conditions,
possibly through their inhibition of tumour necrosis factor alpha (TNF-alpha)
release, which has been shown in macrophages. A3 receptor antagonists might be
useful in treating asthma or acute brain ischaemia. Recently, the versatility of
A3 receptor agonists, administered either before or during ischaemia, in
eliciting potent cardioprotection has been shown.
PMID- 9652193
TI - Drug overdoses requiring temporary cardiac pacing; a study of six cases treated
at Altnagelvin Hospital, Londonderry.
AB - Drug overdoses in general are increasing and overdoses of cardiac medications are
also increasing; some are associated with a high mortality. Temporary cardiac
pacing has a valuable role in cases of hypotension related to dysrhythmia, or
when it is necessary to provide overdrive pacing. However, despite technically
successful and uncomplicated pacemaker insertion and restoration of cardiac
electrical activity, patients developing bradyarrhythmia and hypotension after an
overdose are in a high risk group.
PMID- 9652194
TI - A review of direct current cardioversions for atrial arrhythmia.
AB - The risk of arterial embolism is well recognised following Direct Current
Cardioversion (DCC) for atrial fibrillation although the use of prophylactic
anticoagulation remains controversial. AIM: To determine the risk of arterial
embolism post-cardioversion and which factors predict successful cardioversion
and maintenance of sinus rhythm. MATERIALS AND METHODS: A retrospective study was
carried out of all cardioversions performed for atrial fibrillation and atrial
flutter at the Waveney Hospital Ballymena, during 1989-1993. A review of medical
records and electrocardiograms was carried out to assess demographic
characteristics, co-existent diseases, anticoagulant status, echocardiographic
features and characteristics of the arrhythmia. Embolic events in the six weeks
post-cardioversion were noted. RESULTS: The study included 157 cardioversions in
109 patients. The predominant arrhythmia was atrial fibrillation (n = 108, 69%).
Three of 109 patients (2.7%) experienced embolic complications, none of whom had
anticoagulation prior to the procedure. No risk factors for cerebro-vascular
disease or significant valvular heart disease were present. Return to sinus
rhythm was achieved in 143 (91%) procedures. Increasing coarseness of atrial
fibrillation was associated with a non-significant trend towards successful
restoration of sinus rhythm (p = 0.18). Recurrence of the original arrhythmia was
predicted by an increase in coarseness of atrial fibrillation (p < 0.05).
CONCLUSIONS: These findings indicate that embolic complications can occur in
patients undergoing DCC with normal echocardiographic dimensions, and that
prophylactic anticoagulation should be considered in all patients. Coarseness of
atrial fibrillation may be used as a guide to predict the chance of successful
cardioversion and of the likelihood of maintaining sinus rhythm once this has
been achieved.
PMID- 9652195
TI - The haematuria clinic--referral patterns in Northern Ireland.
AB - One hundred consecutive patients with haematuria were seen over a three month
period at the haematuria clinic, Belfast City Hospital. 14% of patients were
found to have transitional cell carcinoma of the urinary bladder; all of these
presented with frank haematuria and were over 50 years of age. No malignancy was
detected in the microscopic haematuria group. 14% of patients with macroscopic
haematuria held back for longer than one month before seeking advice from their
general practitioner. 23% with macroscopic and 30% with microscopic haematuria
had their symptoms noted by the general practitioner for more than a month before
they were referred for investigation. The waiting time for initial investigation
at the haematuria clinic took longer than six weeks in 52% with macroscopic and
39% with microscopic haematuria. Our study has identified a high-risk group who
need immediate referral and investigation. The importance of patient education,
rapid referral by general practitioners and also the need to increase the
capacity of the haematuria clinic are emphasized.
PMID- 9652196
TI - Trans-cervical resection of the endometrium: the first four years' experience at
the Belfast City Hospital.
AB - We have evaluated the quality of service provided in performing trans cervical
resection of the endometrium (TCRE) in the treatment of women presenting with
menstrual dysfunction. Of the 78 patients who underwent TCRE, ten had, at the
time of writing, subsequently undergone hysterectomy. A chart review was carried
out on those patients. Two others were on the waiting list for hysterectomy.
Sixty-one of 68 (90%) patients responded to the postal questionnaires. Of these,
50 (82%) were satisfied with the result of the procedure. Twenty-three (38%) were
rendered amenorrhoeic. Thirty-eight still had bleeding, but of these, 19 (31%)
had very light regular periods and 13 (21%) had only an occasional stain.
Overall, 90% of women felt that there had been an improvement in their bleeding.
Six (10%) women claimed that there had been no improvement. TCRE is a safe and
effective alternative to hysterectomy or medical treatment for the treatment of
menstrual dysfunction.
PMID- 9652197
TI - The effects of depression awareness seminars on general practitioners knowledge
of depressive illness.
AB - The Royal Colleges of Psychiatry and General Practice wish to increase knowledge
of depressive illness among patients and professionals. This study reports the
results of a series of depression education seminars in a Health Board in
Northern Ireland. Seminars lasted 2 1/2 hours and included didactic teaching and
interactive case management vignettes. 88 general practitioners took part (39% of
those eligible). Seminars increased knowledge as measured by questionnaire
immediately, but this did not appear to be sustained at one year, when compared
to a group of general practitioners with no access to such seminars. Educational
programmes as described do not appear to have a sustained effect on general
practitioners' knowledge of depressive illness.
PMID- 9652198
TI - A prospective study of the process of assessment and care management in the
discharge of elderly patients from hospital.
AB - Assessment and care management (ACM) of elderly patients prior to discharge from
hospital has been in place since 1993. It involves a complex multi-disciplinary
assessment of needs which may delay discharge from hospital. We prospectively
studied the process of ACM in a group of patients discharged from hospital over a
three month period. The times taken for completion of the necessary reports, and
any delays in the process were recorded. The times of each individual step in the
process were correlated to overall length of stay and to the length of the care
management process. The effect of intercurrent illnesses or other delays was
studied. Of the available sample (n = 83), 16 patients died and two required long
term hospital care. The median length of stay of the remainder (n = 65) was 36
days (range 5-149 days). The median time from the start of the ACM process to
discharge was 22 days (0-89 days). The strongest correlation with total length of
stay was the time from admission until ACM commenced (rho = 0.661, p < 0.0001).
The time spent in the ACM process was related strongly to the time taken for the
Care Manager to process the applications (rho = 0.682, p < 0.0001). Delay was
recorded in 17 (24%) cases, resulting in an increased length of stay (p < 0.001).
While care management may help in appropriate placement after hospital discharge,
these results suggest that it is prone to delays outside the hospital setting.
Such delays result in patients waiting in hospital for care packages to be set up
in the community. This has implications for acute hospital services.
PMID- 9652199
TI - Audit of the management of spontaneous pneumothorax.
AB - This audit suggests that clinical practice in the management of spontaneous
pneumothorax differs from guidelines issued by the British Thoracic Society. In
particular simple aspiration was attempted in only seven out of 65 patients and
clamping of an intercostal chest drain occurred in 12 out of 50 cases. Junior
medical staff require more training in intercostal drainage.
PMID- 9652200
TI - An audit of acute psychiatric admission bed occupancy in Northern Ireland.
AB - The Northern Ireland Section (Irish Division) of the Royal College of
Psychiatrists were requested to investigate apparent increasing pressures on
acute psychiatric beds. Information on bed occupancy and associated service
activity was collected by clinicians on site in every psychiatric unit in
Northern Ireland over the past eight years. Three separate years (1987, 1991 and
1995) were studied. Bed occupancy rose across these three years. There was an
associated reduction in the number of acute psychiatric beds, reduction in adult
continuing care beds, increased recorded referrals to psychiatric units and
evidence of considerable numbers of new long-stay patients and difficulties with
community placements. Acute bed occupancy in Northern Ireland is high, frequently
over 100% and rising. Occupancy rose between each of the years studied. The
problem is not confined to urban areas and several associated service factors may
be contributing. Without change, acute bed provision will inevitably fail to
match mental health needs.
PMID- 9652201
TI - Anaesthesia and the broken hearted. 170th annual oration: Royal Victoria
Hospital, Belfast 2nd October 1997.
PMID- 9652202
TI - The successful use of spinal cord stimulation to alleviate intractable angina
pectoris.
PMID- 9652203
TI - Primary breast lymphoma.
PMID- 9652204
TI - Hypoparathyroidism--presenting 40 years after thyroid surgery.
PMID- 9652205
TI - Leprosy elimination campaigns (LECs). Progress during 1997-1998.
PMID- 9652206
TI - Dengue and dengue haemorrhagic fever, Malaysia.
PMID- 9652207
TI - Smallpox eradication--a cold war victory.
PMID- 9652208
TI - Organ transplantation in developing countries.
AB - Organ transplantation has become an effective means of restoring health and
saving lives, but a number of difficulties remain to be overcome. Especially in
developing countries, greater clarity is needed on the sociocultural, economic,
ethical, legal and technical factors involved.
PMID- 9652209
TI - Culture and psychology in organ transplantation.
AB - The cultural and psychological dimensions of organ transplantation are often
overlooked in the process of meeting its exacting technical requirements. This
new branch of medicine has brought with it new ways of understanding death, human
rights, commerce, gift giving, and ethics. It produces strong emotions in
recipients, donors and transplanters alike. These factors need to be taken fully
into consideration if organ transplantation is to evolve in ways that are felt to
be beneficial for all concerned.
PMID- 9652210
TI - A halfway house for pregnant women.
PMID- 9652211
TI - Saving mothers' lives: things can go wrong.
AB - One of the goals of Sierra Leone's primary care programme, established in the
1980s, was to reduce maternal mortality by 30% by the end of the twentieth
century, but no significant progress has been made in this direction. The reasons
are examined below in the light of a study conducted in one of the country's
Chiefdoms.
PMID- 9652212
TI - WHO at fifty. Highlights of activities from 1961 to 1973.
AB - In this second article to mark the fiftieth anniversary of the World Health
Organization in 1998, World Health Forum briefly reviews the work of the
Organization, highlighting some of the wide range of activities carried out or
promoted by WHO from 1961 to 1973. This period covers the remaining years of Dr
M.G. Candau's tenure as Director-General and the appointment of Dr Halfdan T.
Mahler who succeeded him on 21 July 1973.
PMID- 9652213
TI - District hospitals in Turkey.
PMID- 9652214
TI - Effect of referral on deaths from cholera.
PMID- 9652215
TI - Research to prevent injuries.
PMID- 9652216
TI - Structural adjustment and health.
PMID- 9652217
TI - Protecting the world's children: the story of WHO's immunization programme.
AB - Systematic immunization on a worldwide scale was not officially recognized as a
practical possibility until 1974, when WHO launched its Expanded Programme on
Immunization. Today, 80% of the world's children receive this form of protection
against childhood diseases during their first year of life. Coverage can reach
90% by the year 2000, the effectiveness of the vaccines used is improving, and
vaccines against additional diseases are being added to the programme.
PMID- 9652218
TI - From disease control to child health and development.
AB - The control of diarrhoeal diseases, acute respiratory infections and other
childhood killers--such as measles, malaria and malnutrition--is now combined in
WHO's Division of Child Health and Development. The need for integrated
management of childhood illness is shown in its historical context.
PMID- 9652219
TI - The poorest first: WHO's activities to help the people in greatest need.
AB - Through its Division of Intensified Cooperation with Countries and Peoples in
Greatest Need, WHO is giving special attention to the relationship between
poverty and ill-health. The work of the Division is outlined in the present
article.
PMID- 9652220
TI - All hands against polio.
AB - The students and faculty of the Aga Khan University School of Nursing, working in
collaboration with other groups and organizations, have made a considerable
contribution to Pakistan's polio immunization programme in the area of District
Council West and Malir, Karachi. Recommendations for improving the programme are
presented on the basis of the experience gained.
PMID- 9652222
TI - Free high-tech health care in India.
AB - The Sri Sathya Sai Institute of Higher Medical Sciences in Andhra Pradesh can
claim to have achieved the impossible--namely, the provision of high-tech medical
services completely free of charge. Adherence to the five human values (truth,
righteousness, peace, love and non-violence) and complete dedication to serve
people without self-interest are the key elements for this success. This example
may serve as a model for creating similar hospitals in the service of mankind.
PMID- 9652221
TI - Onchocerciasis control in Uganda.
AB - In 1990 a community-based programme of onchocerciasis control, involving the use
of ivermectin, was introduced in Uganda. The problems confronting it are
discussed and suggestions are made for making it sustainable.
PMID- 9652223
TI - Forms of better care.
AB - The introduction of forms called critical care pathways into the paediatric unit
of a hospital in Malawi has strengthened teamwork and helped to increase the
efficiency with which resources are employed. They serve the dual function of
indicating good management and providing an opportunity to note actions and
potential progress.
PMID- 9652224
TI - Emergency health training programme for Africa.
PMID- 9652225
TI - Progress in leprosy elimination.
PMID- 9652226
TI - Counterfeit pharmaceutical products.
PMID- 9652227
TI - AIDS in Africa.
PMID- 9652228
TI - Anti-personnel mines.
PMID- 9652229
TI - Chromosomal structure and recombination between inversions in Drosophila
subobscura.
AB - Drosophila subobscura is a species with rich chromosomal polymorphism. More than
45 arrangements have been described in the O chromosome. The recombination
between them is an interesting topic, because many nonoverlapping arrangements
are inherited together. In the analysis of recombination between the arrangements
O7 and O3 + 4 + 8, out of 415 individuals observed none was found to be
recombinant. The same result was obtained in the study of the recombination
between the inversions O5 and O3 + 4, in which 437 individuals were analyzed. In
this case a significant non equivalent segregation was found, the O5 chromosomes
being more frequent than expected. This phenomenon could be explained by three
hypotheses: a meiotic drive, a greater fitness of the individuals carrying this
inversion and heterotic effect of a wild chromosome in combination with a
chromosome from an inbred laboratory strain. If the second hypothesis is correct,
it could explain why an inversion always associated with a lethal gene in
American populations is not infrequent and presents a clinal distribution in the
colonized areas. Furthermore, another inversion, O22, is very similar to O5.
These two inversions can be distinguished only by careful observation. Although
O22 and O5 are very similar they show different behavior in the wild, probably
due to the combinations of genes included in them.
PMID- 9652230
TI - Sexual selection related to developmental stability in Drosophila buzzatii.
AB - Relationships among developmental stability, sexual selection, and body size were
examined in the cactophilic fly Drosophila buzzatii. Developmental stability, as
measured in terms of fluctuating asymmetry (FA) of wing length, was positively
associated to male's copulatory success in a mass-mating experiment with wild
reared flies. Previous studies showed that body size is positively correlated
with mating success and other fitness components in this species, but no
phenotypic correlation between wing asymmetry and size was found in the present
study. Thus, wing asymmetry does not indicate male quality in terms of phenotypic
variation in body size. This study suggests that sexual selection against wing
asymmetry may be mediated through unknown factors related to developmental
stability rather than body size.
PMID- 9652231
TI - Characterization of cCel3, a member of the pepper endo-beta-1,4-glucanase
multigene family.
AB - In pepper plants the enzyme endo-beta-1,4-glucanase (EGase) is encoded by a
multigene family. Here is described the characterization of cCel3, a cDNA which
codes for the third EGase known so far in this plant. The known members of this
family are present as single copy genes, as demonstrated by a Southern analysis
of the genomic DNA. Analysis of the expression of cCel3 demonstrates that the
highest levels of the cCel3 mRNA are found in abscission zones of leaves and
flowers activated by treatments with the plant hormone ethylene. However, the
amounts of the cCel3 transcripts (detectable only by RT-PCR) are always much
lower than those of cCel2 so that the latter can be regarded as the "abscission"
EGase while cCel3 is likely to perform a role ancillary to that of cCel2.
PMID- 9652232
TI - Cytoplasmic diversity in leaf beet cultivars as revealed by mitochondrial DNA
analysis.
AB - Mitochondrial (mt) DNA restriction fragment length polymorphisms are convenient
markers for identifying cytoplasmic variation among plant cultivars. In an
attempt to detect new cytoplasmic genotypes useful for sugarbeet breeding, we
have compared the hybridization patterns of mtDNA from three groups of cultivated
beets, viz. leaf beet, garden beet, and fodder beet. Utilized as probes were the
two sugarbeet mtDNA clones that were capable of distinguishing normal fertile and
different sources of male-sterile cytoplasms from one another. The analysis
allowed the identification of four chondriome types among 14 leaf beet cultivars
examined. Two out of the four chondriome types were found to be different from
the previously described fertile or male-sterile chondriome type. Our results
thus indicate that leaf beet cultivars and landraces make up the primary
cytoplasmic gene pool of the sugarbeet.
PMID- 9652233
TI - Mitochondrial control region polymorphism reveal high amount of gene flow in
Fennoscandian willow tits (Parus montanus borealis).
AB - We studied the genetic variability and differentiation of two Fennoscandian
willow tit (Parus montanus borealis) populations located ca. 1000 km apart in
Finland and Sweden by using the control region sequences of the mitochondrial
DNA. Individual variation in the control region was extensive since all the 13
Finnish and the 12 Swedish individuals had unique haplotypes and the mean
pairwise genetic distance resulted in 0.0052 (range 0.0008-0.0109). In the
minimum spanning network connecting the genotypes, the two populations were
completely intermingled. The mismatch distribution of the combined data set was
very close to expected distribution of an expanding population. This result was
supported by a significantly negative Tajima's D value. The sequence data
indicate that (1) the long-term effective population size of the breeding willow
tits has been large (122,000 and 110,000 females for the Finnish and the Swedish
populations, respectively); and that (2) the gene exchange between distant
localities is/has been extensive. Dispersal area for the Finnish females was
estimated to be about 19,000-30,000 km2 and for the Swedish, 22,000-28,000 km2.
Thus, the whole Fennoscandian population can be regarded as one panmictic unit,
without any subdivisions to local demes. The amount of gene flow is remarkable
because the willow tit has been considered a highly sedentary species. Provided
that adult birds are site-tenacious, the gene flow must occur through juvenile
summer dispersal, or irruptive autumn invasions, or both.
PMID- 9652234
TI - Detection of individual variation in enzyme activity in natural populations of
Drosophila melanogaster.
AB - The method allows the determination of the activity level of enzymes in a single
fly and assessing the genetic composition of the given individual at these enzyme
loci. Three isofemale lines were constructed which were monomorphic at several
enzyme loci. Samples were prepared in two different ways: (i) individual samples-
individuals were homogenised separately; (ii) collective samples--a common
homogenate was prepared from several individuals. Oregon-R strain was also used
to prepare a standard homogenate. The activities of alcohol dehydrogenase (ADH),
alpha-glycerophosphate dehydrogenase (alpha GPDH), isocitrate dehydrogenase
(IDH), and 6-phosphogluconate dehydrogenase (6PGDH), were measured in each sample
on starch gel after the proteins were separated by electrophoresis. Enzyme
activities were assessed by the optical density of the bands. Gel and position
weights were estimated on the basis of the statistical analyses of the activities
measured in the standard samples. Gel weights were then used to account for the
activity differences among the gels while position weights were applied to
correct for the general tendencies in the activities observed within the gels.
The gel and position weighted activities of individual and collective samples
were compared in the isofemale lines. The individual samples had approximately
two times as much variation as the collective samples for all four enzymes. The
electrophoretic method is sensitive enough to study the structure of the
phenotypic variation in enzyme activity in the natural populations. The total
variation among the standard samples was close to the within subline component of
variation obtained for the collective samples (measurement error). This shows
that the standard samples can be used to estimate the size of the measurement
error.
PMID- 9652235
TI - Mutants and duplication in chromosome 7 (syn. 5H) in the barley line HA21:
duplications may enhance QTLs and serve to make constant linear cis
heterozygosity.
AB - Cytological and linkage data indicate a duplication in the short arm of
chromosome 7 (syn. 5H) in the mutant line HA21 (barley, Hordeum vulgare, cv.
'Pirkka'). The associated mutant (ha21) shows a weighted average linkage of 22.1
cM with pld, hitherto an ignored anthocyaninless gene, of cv. Pirkka. Some
crosses produce F2 segregants with an exaggerated ha21 phenotype which may
represent position effect or increased dosage of the mutant gene through
recombination. Compared with cv. Pirkka, HA21 has changes in grain chemistry
(alpha- and beta-amylase, beta-glucanase), which may be caused by changed QTL
dosage or QTL position effect due to duplication. The use of duplication in
creating constant +m/+ m or m+/m+ linear cis-heterozygotes is suggested. Linear
cis-heterozygotes may produce stable heterosis or attenuate the undesired effects
of drastic mutants.
PMID- 9652236
TI - Treatment of hand and wrist pain. A randomized clinical trial of high voltage
pulsed, direct current built into a wrist splint.
AB - To determine the effectiveness of high voltage pulsed current (HVPC) in reducing
chronic hand edema, 120 individuals were randomly assigned to one of two
treatment groups. Group I clients were given an appropriate sized wrist splint,
incorporating an energized, high voltage pulsed unit. Group II clients were given
an identical splint with a non-energized unit. Each client received daily
treatments at the worksite consisting of 30 minute sessions totaling 20
treatments during a 35 day period. Pre-treatment and post-treatment evaluations
included measurements of pain, grip strength, and edema volume; repetitive task
testing; and Semmes-Weinstein Monofilament sensory testing. In the energized
group, post-treatment evaluation showed statistically significant decreases in
the amount of stimulation required to stimulate the median nerve and the amount
of hand edema and pain. The energized group also had improved repetitive task
times. None of these improvements occurred in the non-energized group. Based on
these results, HVPC appears to be an effective method for minimizing the severity
of repetitive stress injuries of the wrist.
PMID- 9652237
TI - Effectiveness of a worksite smoking cessation program in the military. Program
evaluation.
AB - 1. A program evaluation was conducted to evaluate the effectiveness of the
smoking cessation program. Substantiating data enhances the value of health
promotion programs as key components of the health care delivery system. 2.
Persons enrolled in the 8 week smoking cessation program and members of a
comparison group were administered an evaluation tool prior to participating in
the program, with a second evaluation tool upon completion of the program.
Afterward, the smoking status of the members of both groups was evaluated at 3
month intervals for a period of 1 year. 3. Of the participants, 26.7% were not
smoking 12 months after the program, compared to 6.9% of the comparison group. Of
those participants who resumed smoking, 64% smoked less than half the amount they
smoked before taking the class.
PMID- 9652238
TI - Occupational exposure of health care workers to bloodborne pathogens. A proposal
for a systematic intervention approach.
AB - 1. Each year approximately 6,500 to 9,000 health care workers in the United
States are exposed to infectious body fluids while on the job. The majority of
the resultant clinical infections causing morbidity and mortality are
attributable to bloodborne pathogens. 2. The relatively simple approach of
educating workers so they comply with exposure control systems has continued to
be employed by many infection control and employee health specialists, despite
the temporary and/or negligible effects demonstrated from high risk health care
employees. 3. The reduction of worksite transmission of bloodborne pathogens
through the increased use of system wide and worksite engineering techniques has
been advocated by experts, demanding increased consideration from health care
planners and researchers.
PMID- 9652239
TI - Non-steroidal antiinflammatory drugs. A review.
AB - 1. Non-steroidal antiinflammatory drugs (NSAIDs) are among the most frequently
prescribed medications and are used primarily to control pain, stiffness, and
reduce inflammation. 2. One of the most common adverse effects of NSAID therapy
is gastrointestinal (GI) problems, specifically indigestion, nausea, dyspepsia,
diarrhea, constipation, and gastritis. 3. Considerations in chronic pain
management include non-pharmacologic treatment options (i.e., physical therapy,
behavioral therapy, etc.), use of misoprostol for clients at high risk for NSAID
induced GI problems, and monitoring blood and urine every 3 months to 1 year with
chronic NSAID therapy to detect liver, kidney, and hematologic problems. 4.
Current research is focused on development of a prostaglandin H synthetase (PGHS
2) inhibitor which should offer efficacy equal to the most potent NSAIDs with
minimal side effects, including gastric safety.
PMID- 9652241
TI - Descriptive analysis of research data.
PMID- 9652240
TI - Avoiding the millenium bug.
PMID- 9652242
TI - Project management, Part III. Budgets for projects.
PMID- 9652243
TI - The truth ... the whole truth.
PMID- 9652244
TI - Rehabilitation of an adolescent with medulloblastoma.
PMID- 9652245
TI - A multidimensional measure of fatigue for use with cancer patients.
AB - PURPOSE: The purpose of this study was to develop and validate a multidimensional
measure of fatigue for use with cancer patients. DESCRIPTION OF STUDY: Items for
the Multidimensional Fatigue Symptom Inventory (MFSI) were generated through
literature review, discussion with healthcare providers, and a survey of
currently available measures of fatigue. The 83-item MFSI was designed to assess
global, somatic, affective, cognitive, and behavioral symptoms of fatigue. The
instrument was administered on three occasions to 275 women who had received or
were undergoing treatment for breast cancer and 70 women with no history of
cancer. Reliability, validity, and factorial structure of the MFSI were analyzed.
RESULTS: The factor analysis produced five empirically derived scales that
correspond generally to the five rationally derived scales. Reliability of the
rationally and empirically derived scales was excellent (alpha coefficients .87
to .96). Estimates of test-retest reliability were also favorable. Other results
support the validity of both the rationally and empirically derived scales. The
MFSI appears to be sensitive to fatigue, accurately discriminating cancer
patients from control subjects and between patients with varying levels of
performance status. CLINICAL IMPLICATIONS: The MFSI may be useful in identifying
patterns of fatigue within individual patients and across treatment modalities.
Such specificity may allow the clinician to develop, implement, and evaluate
interventions that are targeted for differing patterns of fatigue. Because the
measure is keyed to a 1-week time frame, it may be useful during the course of
cancer treatment. The MFSI appears to be a valid and reliable tool to assess the
full spectrum of symptoms that characterize the construct of fatigue.
PMID- 9652246
TI - Cross-cultural issues in the disclosure of cancer.
AB - PURPOSE: To increase awareness of cultural differences in the disclosure of a
cancer diagnosis or prognosis, the author reviews several surveys of patients and
physicians from around the world. OVERVIEW: The Western medical community is
increasingly emphasizing full truthful disclosure of cancer diagnoses or
prognoses and respect for autonomy as necessary prerequisites to ethical
practice. However, surveys of European, Japanese, Native American, and various
ethnic American (including Korean, Chinese, Mexican, Hispanic, African, and
European American) cancer patients and physicians reveal that many cultures
consider complete and accurate disclosure of cancer undesirable. Cultural
differences in the rates of disclosure of a cancer diagnosis or prognosis; the
physician's use of euphemisms to give a true or false diagnosis; as well as
considerations of how to disclose a cancer diagnosis are described. CLINICAL
IMPLICATIONS: Developing an awareness about cross-cultural practices regarding
cancer disclosure issues allows the clinician to become more sensitive to the
expectations of culturally and individually diverse cancer patients. To this end,
all healthcare professionals should be informed about how the patient would like
to be informed of a diagnosis and how involved he or she would like family
members to be. In addition, an awareness of the use of nonverbal communication in
some cultures and the psychosocial impact of certain terms, such as "cancer," is
essential. Often, phrases such as "malignant tumor" or "growth" are less
inflammatory and are more readily accepted. In ascertaining a knowledge of
various cultural preferences and developing a sensitivity to these preferences,
clinicians are better able to provide effective care to individuals from a
variety of cultural and individual backgrounds.
PMID- 9652247
TI - Selecting and implementing support groups for bereaved adults.
AB - PURPOSE: This paper offers a rationale for initiating bereavement support groups
in sites providing cancer care and delineates models to implement them. Skills
needed to lead a bereavement support group are identified, with emphasis on
adding to staff members' competency that has already been developed by
facilitating groups for oncology patients and their families. OVERVIEW:
Bereavement support groups are essential elements in the provision of
comprehensive oncology care, though they are seldom offered by staff in the
traditional hospital setting. It is important that the bereaved feel that there
is a place in which they have the time and understanding required to work through
the normal grieving process. Special requirements for facilitators include self
awareness of the impact of loss in their own lives and ability to tolerate both
the emotions expressed in the grieving process and the often extended time period
required for members' personal healing. Several bereavement support models,
including the time-limited, ongoing, monthly, and self-help groups, are
documented. CLINICAL IMPLICATIONS: Bereavement support is an essential element in
the provision of comprehensive oncology care. Predictive models to identify
individuals who are at higher risk for psychological distress could be used in
oncology clinics to facilitate early referral or greater psychological support
for family members. Staff members wishing to introduce this service can build on
skills already developed leading traditional oncology support groups, and can
utilize cofacilitation with a mental health professional to ease the anxiety of
assuming a new role and obtain mentoring. Recruitment for a group might be
achieved by inviting family members of patients who have died within a specific
time frame or by issuing press releases to local papers and church bulletins.
Offering bereavement support in the oncology setting is especially helpful to
family members who might otherwise be unaware of such a service and who now have
the opportunity to attend.
PMID- 9652248
TI - Colorectal cancer screening. Knowledge and practices among Korean Americans.
AB - PURPOSE: The purpose of this study was to examine knowledge and practices of
colorectal cancer screening among Korean Americans. DESCRIPTION OF STUDY: The
sample consisted of 104 Korean American men and 159 women, 40 to 69 years of age,
living in the Chicago area. The National Health Interview Survey (NHIS) Cancer
Control Supplement Questionnaire, prepared by the National Center for Health
Statistics, was used to collect data regarding colorectal cancer screening
knowledge and practices. The NHIS questionnaire was translated into Korean with
minor modification. RESULTS: The percentage of male respondents ever having had a
digital rectal exam (DRE) and fecal occult blood test (FOBT) were 13.5% and
10.6%, respectively. Only 11.3% of women reported DRE and 8.8% FOBT. Multiple
logistic regression analysis results indicate that gender, education, knowledge
of the seven cancer warning signals, and length of residence in the United States
were significantly related to having heard of DRE. For those having had DRE,
knowledge of the seven cancer warning signals, and length of residence in the
United States were the only significant variables. Gender and education were
significantly related to having heard of FOBT. None of the variables were found
to be significantly related to having had FOBT. The findings indicate that a
majority of respondents were unaware of these cancer screening examinations and
forego these tests due to an underestimation of their importance. CLINICAL
IMPLICATIONS: The findings of this study underscore the importance of cancer
education and further research addressing the cancer screening needs of Korean
Americans. Currently, Korean Americans do not see healthcare providers or health
brochures as valuable sources of health information. Therefore, healthcare
professionals need to target this population by 1) coordinating their efforts
with church and other community leaders and 2) developing health brochures that
are in the Korean language and sensitive to the Korean culture.
PMID- 9652249
TI - Alternative care. Patient choices for adjunct therapies within a cancer center.
AB - PURPOSE: Prompted by an increased interest in and awareness of alternative
medicine, the Sutter Cancer Center in Sacramento, California, sponsored a
telephone survey of its cancer patients. The primary purpose of this 1994 survey
was: 1) to determine patient perceptions and attitudes regarding alternative care
providers, and 2) to determine whether the Sutter Cancer Center should provide
support for these types of therapies to its patients. DESCRIPTION OF STUDY: The
Center conducted a 95-item telephone survey of its patients with cancer, using an
independent professional research firm. A random sample of 503 adult patients
completed the 15-minute telephone survey between January 27 and March 8, 1994.
The sample included more women than men (62%, 38%, respectively), and patients
ranged in age from 18 to 88 years. All respondents had been treated for cancer at
the Center within the past 2 years. Survey questions included areas such as
cancer diagnosis, awareness of alternative therapies, attitude toward alternative
therapies, and perception of oncologists' attitude toward alternative therapies.
The analysis of the survey results contained two phases: descriptive analysis and
comparative analysis. The descriptive aspect is included in this report. RESULTS:
Of the 503 respondents, 82 (16%) had considered utilizing alternative therapy for
cancer after a diagnosis was made. Most respondents were moderately familiar with
alternative therapy, such as nutrition therapy (59%), herbal therapy (63%), and
acupuncture (62%). Only 6% of respondents actually saw a provider of alternative
therapies; providers were most frequently nutritionists, counselors, herbalists,
and massage therapists. The user patient profile clearly indicates that usage is
highest in patients with a diagnosis of at least 1 year. Seventy-five percent
reported that they would prefer to receive a referral from their doctors, while
20% would prefer to use a telephone referral line. Two thirds of patients felt
that alternative care providers should be encouraged by the medical profession,
and 85% indicated that alternative care should be offered at the cancer center as
part of oncology treatment. CLINICAL IMPLICATIONS: The results of this survey
clearly reflect the patients' desires to integrate mainstream medicine with some
forms of alternative/complementary medicine. Consequently, the Sutter Cancer
Center has established a multidisciplinary group of healthcare professionals,
including oncologists, nurses, social workers, and alternative practitioners, to
evaluate the clinical, psychosocial, and financial impact of integrating
wellness/complementary medicine into the existing treatment model at this
facility. Providing alternative therapy within a cancer center ensures the
availability of both the most advanced conventional treatment and care as well as
accurate information and guidance with regard to alternative therapies. This
service allows the patient and the cancer care team to focus not only on the
patient's physical symptoms, but also on his or her overall quality of life.
PMID- 9652251
TI - End-of-life care: hospice or home?
PMID- 9652250
TI - Cost considerations as potential barriers to cancer treatment.
AB - PURPOSE: An analytical cross-sectional survey was conducted to determine the
prevalence of barriers to cancer treatment in Texas as perceived by diagnosed
cancer patients. Results reported here address the role of insurance coverage,
indirect costs (transportation, lodging, and work days lost), and direct costs of
care as barriers to treatment for white, black, and Hispanic cancer patients.
Specific objectives of the analyses undertaken here are to examine 1)
racial/ethnic differences in insurance coverage; 2) barriers relating to
insurance coverage experienced by cancer patients; and 3) role of treatment
related costs as barriers to cancer treatment. DESCRIPTION OF STUDY: A mail
questionnaire was developed to assess the perceived barriers to cancer treatment
in Texas for adult cancer patients, 17 years and older, who had been diagnosed
with breast, colon, cervical, prostate, or lymphoma during the period of 1989 to
1993. The sampling frame for this study was obtained from a network of cancer
treatment facilities throughout the state of Texas within the University of Texas
M.D. Anderson Cancer Center Texas Community Oncology Network. A total of 593
cancer patients returned their surveys, yielding a 65.2% response rate. Weighting
adjustments were then made to correct for differential sampling and response
rates by racial groupings and type of cancer. All of the analyses used adjusted
weights. RESULTS: The findings document the financial considerations (insurance,
direct and indirect costs) as they relate to barriers to cancer treatment.
Specific insurance premium-related barriers with regard to maintaining and
affording coverage were more prevalent for blacks. Hispanics were less likely to
have insurance coverage; however, more blacks reported being denied insurance
coverage when they changed jobs compared with whites and Hispanics. Minorities,
particularly Hispanics, were more likely to have experienced cost-related
barriers associated with medications, diagnostic tests, and hospitalizations. In
addition, Hispanics experienced significant out-of-pocket costs in paying for
cancer treatment. CLINICAL IMPLICATIONS: This research shows the need for staff
at cancer treatment facilities to be aware that there are nonclinical, financial
factors that are important considerations in the treatment of cancer patients.
Assessment of cancer patients during the diagnostic and treatment stages,
possibly through case management, will provide information on potential barriers
to treatment for individual patients. Hospital programs that reimburse out-of
pocket costs, transportation costs to obtain services, and lodging accommodations
may be available. Additional services may be offered through cancer advocacy
groups, such as the American Cancer Society and the National Coalition for Cancer
Survivors, to assist patients with managing costs and overcoming barriers to
care.
PMID- 9652252
TI - Culturally relevant "Navigator" patient support. The Native sisters.
PMID- 9652253
TI - Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma.
AB - Rituximab is an effective single agent available for short-course outpatient
treatment in low-grade NHL, particularly with follicular histology (IWF B-D),
that offers a relatively nontoxic alternative to chemotherapy regimens currently
available. Early indications are that retreatment is effective with similar
levels of predictable adverse events to the initial course of therapy. Further
development is awaited of regimens that combine rituximab with chemotherapeutic
agents to enhance treatment efficacy without overlapping side effects in low
grade NHL as well as use in other CD20+ malignancies.
PMID- 9652254
TI - The debate of the age: the ageing population.
PMID- 9652255
TI - Parental presence during resuscitation: attitudes of staff on a paediatric
intensive care unit.
AB - Although family presence during resuscitation is becoming more acceptable, many
medical and nursing staff still have concerns and doubts about it. To ascertain
paediatric medical and nursing staff's attitudes towards parents being present
during resuscitation, 60 staff in a Paediatric Intensive Care Unit were surveyed.
The results revealed that even though 89% of staff feel that parents should be
able to be present, many have the same concerns and doubts that have been
highlighted in previous, albeit adult-centred, studies. Increased stress to staff
and parents were some of the concerns identified in a study which also showed
interest in the subject and a need for further education.
PMID- 9652256
TI - Parental anxiety due to abnormal behaviour following withdrawal of sedation.
AB - Abnormal behaviour has been previously reported on withdrawal of sedation in
critically-ill children. This description of a child who had prolonged withdrawal
symptoms lasting almost 2 weeks includes a report on his parent's comments in
relation to the anxiety they felt while he was behaving abnormally. Health
professionals need to be aware of the severe nature of this withdrawal reaction
and its effect on the parents.
PMID- 9652257
TI - Role extension or expansion: a qualitative investigation of the perceptions of
senior medical and nursing staff in an adult intensive care unit.
AB - The Scope of Professional Practice (UKCC 1992) has significantly altered the
interpretation of nurses' roles, emphasizing individual professional
accountability and clinical decision-making. However, 5 years after the issue of
the document, uncertainties remain regarding interprofessional legal
accountability between medicine and nursing. To investigate issues surrounding
role extension or expansion in intensive care nursing, a small qualitative study
was conducted centred on one intensive care unit (ICU) within a large teaching
hospital. Data were collected by semi-structured interviews from a purposive
sample of five senior intensive care nurses and three consultant anaesthetists.
Four major categories emerged, identified as: interpretation confusion; education
for change; struggles for power and task versus autonomy. The findings revealed
that the senior critical care nurses identified themselves as independent,
autonomous practitioners involved in clinical decision-making. However, there was
evidence of a reluctance to empower more junior staff to perform extended or
expanded roles. Medical respondents viewed extended or expanded roles as taking
on mechanical tasks for which anyone could be trained to perform. In conclusion,
it is argued that although nursing is maturing in its growth towards
professionalization, broader issues such as the legal quagmire, failure to adopt
the philosophy of role expansion and the existence of sacred boundaries intra-
and inter-professionally need to be addressed.
PMID- 9652259
TI - Establishing evidence-based practice: issues and implications in critical care
nursing.
AB - Evidence-based practice is the application of the best available empirical
evidence, including recent research findings to clinical practice in order to aid
clinical decision-making. The implementation of these findings is vital for
optimizing patient outcomes, improving clinical practice, providing cost
effective high quality care and enhancing the credibility of nurses. The use of
research findings to improve practice has been discussed and promoted for the
last 20 years. The author argues that Rogers' theoretical model of the Diffusion
of Innovations may prove useful in understanding the problem of the slow
diffusion of the application of research evidence in clinical nursing practice.
Many authors have discussed potential barriers to using research in clinical
practice in order to facilitate utilization of findings. However, recent studies
all document that a gap between research findings and their implementation in
clinical practice still exists. This appears to hold true across a variety of
practice settings, including nurses working in critical care. The diffusion of
innovations in current critical care nursing practice at each stage of Rogers'
theory will be examined, with recommendations given to facilitate the
establishment of evidence-based practice (EBP).
PMID- 9652258
TI - Brain death in ICUs and associated nursing care challenges concerning patients
and families.
AB - In order to document the incidence and causes of brain death (BD) and the
frequency of organ donation (OD) in a Swedish University Hospital, a
retrospective review of deaths in a neurosurgical department and in the general
intensive care units (ICUs), was carried out for the period 1988-1994. BD
diagnosis was established in 197 (10.6%) of all deaths (n = 1843). The hospital
records of all BD patients were examined in detail following a specific study
plan. The majority of the BD patients (89%) were acute admissions to hospital,
and among them 81 were transferred between hospitals often over a long distance.
Among the BD patients the total number of OD was 65 (33%). The most common
diagnosis leading to BD was spontaneous intracerebral bleeding and traumatic head
injury. The BD diagnosis was established by neurological examination (60%) and by
cerebral angiography (40%). Of the BD patients, 50% died within 48 hours in the
ICU and the majority of requests for OD (67%) were made to the relatives of these
patients. The findings are discussed with focus on the workload and psychological
stress of ICU nurses when caring for BD patients and their families; a task which
includes taking part in processes concerning BD diagnosis information and OD
requests.
PMID- 9652260
TI - Evidence for the effectiveness of cardiac rehabilitation.
AB - Cardiac rehabilitation is a relatively recent development and, though it is
increasingly being recognized as an important part of comprehensive cardiac care,
there remains some scepticism regarding its effectiveness and some ignorance of
its potential. This article reviews the literature pertaining to the
effectiveness of cardiac rehabilitation for patients with coronary heart disease
(CHD).
PMID- 9652261
TI - Colony stimulating factors: G-CSFs--filgrastim (Neupogen) and lenograstim
(Granocyte).
AB - The introduction of leucocyte growth factors produced by DNA biosynthetic
technology has had a major impact on survival in patients with compromised
immunity. Such agents have maximized the benefits of treatment with drugs which
are otherwise potentially toxic to the bone marrow.
PMID- 9652262
TI - The impact of a hospital-wide experiential learning educational program on
staff's knowledge and misconceptions about aging.
AB - The increased use of health care services by older adults has prompted an
interest in preparing health care workers to better deal with the special needs
of older adults. Aging education is one method of sensitizing health care
personnel to these special needs, but the effectiveness of such educational
programs needs to be established. The purpose of this study was to examine the
impact of the knowledge and attitudes of hospital personnel of their
participation in an experiential learning educational program concerning older
adults. Each of nine groups of hospital employees attended a 2-hour workshop.
Each group completed a pretest and posttest using Palmore's Facts on Aging Quiz.
A significant increase in scores was found in all groups after the workshop
experience, and some groups had a greater increase in scores than others.
PMID- 9652263
TI - Using role theory concepts to understand transitions from hospital-based nursing
practice to home care nursing.
AB - BACKGROUND: The phenomena experienced by professional nurses who make practice
based career changes are seldom addressed in the literature. Nurses changing from
a hospital-based practice to a home health care setting report feelings of
anxiety, incompetency, and lack of the necessary skills to care for clients in
the home. METHOD: An integrative review of the literature on role theory can
provide the conceptual understanding of the transitional experience of nurses
whose roles change when they move from hospital-based practice to a home health
care setting. RESULTS: A model of the role transition process is helpful in
identifying the transition experienced by nurses new to the home health care
setting. Experiences during the initial transition period are critical in shaping
the nurse's understanding of the role. CONCLUSION: Educators can play a key part
in assisting novice home health care nurses with role enactment by developing
comprehensive orientation and education programs aimed at minimizing role strain.
PMID- 9652264
TI - The growth and development of an educational consortium.
AB - This article discusses the beginning and continual evolution of a critical care
educational consortium. Committee membership, curriculum development, and key
service provisions are discussed. This article focuses on the process involved in
the development of an educational consortium and the intended and unintended
outcomes that developed as a result of this joint venture.
PMID- 9652265
TI - Knowledge, perceptions, and practice of nurses toward HIV+/AIDS patients
diagnosed with tuberculosis.
AB - BACKGROUND: Tuberculosis (TB) continues to be a major health problem in the
United States. Nurses may be exposed to TB and not realize their risks for
becoming infected. The presentation of HIV-associated TB is somewhat different
from "standard TB." PURPOSE: The purpose of this study was to determine if an
educational program could improve nurses' attitudes, level of knowledge, and
compliance with infection control standards for HIV/AIDS patients diagnosed with
TB. METHOD: Participants included 50 staff nurses. The experimental group (35)
and control group (15) completed a knowledge test and an attitude survey.
Researchers observed participants for compliance with infection control standards
pretest and posttest. RESULTS: Following an educational program, the experimental
group demonstrated a greater knowledge of TB than the control group who did not
participate in the educational program (F [1.47] = 14.43, p = .000). In addition,
the experimental group had a greater improvement in their Nursing Intervention
Observation Tool adherence to respiratory isolation and universal precaution
protocols scores as compared to the control group (F [1.47] = 8.95, p = .004).
However, there was not a tangible increase in knowledge level of AIDS, attitudes
or concerns about caring for these patients. CONCLUSION: This nursing research
study supports the need for an ongoing educational program with continual
monitoring of infection control practices to positively affect client and
caregiver outcomes.
PMID- 9652266
TI - The patient care assistant program: the nursing profession's and a community
college's response to educating unlicensed assistive personnel.
AB - Preparing unlicensed assistive personnel for work in hospitals is one of the
major challenges facing the nursing profession in the 1990s. Continued debate
prevails over who should educate these health care workers and what content
should be included in the curriculum. The 516-hour course described in this
article was designed by nursing professionals to educate and train individuals to
function as unlicensed assistive personnel in the acute care setting. The program
takes place in a junior college and consists of learning activities in the
classroom, skills laboratory, nursing home, and acute care hospital.
PMID- 9652267
TI - Preparing nurses for the acute care case manager role: educational needs
identified by existing case managers.
AB - BACKGROUND: There is little in the literature about how best to prepare nurses
for case manager roles. METHOD: Twenty acute care case managers were asked to
identify skills and knowledge that would be of value to nurses new to case
manager roles. RESULTS: Community resources, discharge planning, and third party
reimbursement were the top three educational needs identified by all case
managers. Baccalaureate prepared case managers identified clinical issues to be
of value, such as family coping, patient education, quality of life, and social
support, while master's prepared nurses identified only system-related issues.
CONCLUSION: Educational programs preparing baccalaureate prepared case managers
could focus on both clinical and system issues, while programs preparing master's
educated case managers could focus primarily on managing system issues. Staff
development professionals may also call on experts inside and outside the
institution to assist in teaching about health care finance and reimbursement
issues.
PMID- 9652269
TI - Pediatric intravenous nursing.
PMID- 9652268
TI - Integrating ongoing evaluation process for international pediatric nursing
courses.
AB - Two international pediatric courses for nurses from developing countries were
planned and implemented in Israel during the past 2 years. The courses consisted
of 53 RNs from 29 countries. The purpose of this article is to describe the
ongoing evaluation and follow-up process of these courses. Findings indicated
that the majority of nurses expressed: a) high satisfaction with the course and
felt it enhanced their professional capacity and practice, and benefited their
colleagues and superiors; b) high motivation and enthusiasm to improve nursing
practices in their home countries; c) changes in attitudes and beliefs relating
to pediatric nursing.
PMID- 9652270
TI - Indiscriminate use of intravenous hydration in dying patients.
PMID- 9652271
TI - Impact of dressing materials on central venous catheter infection rates.
PMID- 9652272
TI - Pediatric growth hormone deficiency.
AB - Current information on the pathophysiology, diagnostic process, and treatment of
growth hormone deficiency is provided. A case study is provided that shows the
positive effects of growth hormone therapy on a patient and his family.
Information regarding the intravenous clinician's role in administration of
growth hormone and patient teaching also is included.
PMID- 9652273
TI - Emergency access in pediatrics.
AB - Obtaining i.v. access in children during an emergency situation is a challenge to
nurses. It is important for the infusion nurse specialist to understand which
devices and sites are appropriate in different circumstances. This article
addresses the access sites and devices demanded in pediatric emergency situations
and offers an approach to managing the anxiety of children requiring emergency
infusion care and their families.
PMID- 9652274
TI - Fluid and electrolyte balance in the pediatric patient.
AB - Maintaining adequate fluid and electrolyte balance is an important aspect of all
patient care. The intravenous nurse's skill and expertise in starting and
maintaining i.v. access is extremely vital to providing adequate fluids and
electrolytes. Children and infants present unique problems in the management of
fluid and electrolyte balance. Differences in rate of metabolism and body surface
area are just two examples of special circumstances that affect diagnosis and
management. An awareness of predisposing factors, early recognition of signs and
symptoms that may be indicative of a developing problem, and knowledge of medical
and nursing interventions help provide safe patient care. This article presents
unique aspects of caring for infants and children, reviews important
electrolytes, and discusses dehydration.
PMID- 9652275
TI - Success rates for peripheral i.v. insertion in a children's hospital. Financial
implications.
AB - Although many publications have demonstrated the cost-effectiveness of using i.v.
nurse specialists with adult patients, very few have explored this topic in the
pediatric population. Many agencies choose to use staff RNs and physicians, with
minimal training and experience, to place i.v.s in both pediatric and adult
patients. This article demonstrates i.v. insertion success rates for various
healthcare providers: staff RNs, physicians, and an i.v. nurse specialist in an
urban pediatric hospital. The number of unsuccessful i.v. attempts for each group
is calculated and further applied to costs of labor and equipment. From the data
presented in this article, it may be concluded that the use of one or more i.v.
specialist nurses for placement of peripheral i.v.s in children is more cost
effective than using staff RNs or physicians for provision of this service. These
data were collected while the author was the i.v. nurse clinician at St.
Christopher's Hospital for Children in Philadelphia.
PMID- 9652276
TI - Use of in-line filters in pediatric intravenous therapy.
AB - This study arose from a need to justify the extensive use of in-line intravenous
filters in an Australian pediatric teaching hospital. The incidence of septicemia
was observed for two 12-month periods before and after the withdrawal of in-line
i.v. filters from patients with central venous access devices. A total of 19,221
i.v. days were monitored in 88 children in two 1-year periods. No significant
differences were found in the incidence of septicemia between the children who
had filters fitted and those who did not. As a result, the routine fitting of
filters to i.v. lines infusing fluids filtered during manufacture under a laminar
flow has been discontinued with significant cost savings.
PMID- 9652277
TI - Children's drawings: an invaluable source of information for nurses.
PMID- 9652278
TI - Infants with Down syndrome: a look at temperament.
AB - INTRODUCTION: This research describes temperament characteristics of infants with
Down syndrome who are 1 to 4 months old. In the literature children with Down
syndrome have been stereotyped. It was hypothesized that temperament
characteristics may be evident and unique in newborns with Down syndrome. METHOD:
A standardized questionnaire, The Early Infancy Temperament Questionnaire, a
cover letter, informed consent forms, and a brief explanation of the project were
given to families with a newborn infant with Down syndrome. Thirty-two (families
with infants with Down syndrome completed the study. RESULTS: Mean scores
indicate that infants with Down syndrome are rated more active, less intense,
more distractible, and have a tendency to demonstrate more approach behaviors
compared with normally developing infants. Data suggest infants with Down
syndrome have some unique characteristics but are more like their normally
developing peers than different. DISCUSSION: Integration and mainstreaming of
infants and children with Down syndrome emphasizes the need for nurse
practitioners to appreciate the temperament characteristics of these infants.
PMID- 9652279
TI - Parents' perceptions of medical diagnoses and related issues for their high-risk
infants.
AB - INTRODUCTION: The objectives of this study were (a) to compare maternal and
paternal perceptions of infant medical diagnoses with hospital-chart diagnoses,
(b) to examine whether parental perceptions of infant medical condition (using
three variables) were related to eight other parental perceptions, and (c) to
determine what medical diagnoses were associated with parental expectations that
neonatal diagnoses were having current effects of would have future effects on
their infant. METHOD: With a questionnaire format 76 parents reported information
about medical diagnoses and their perceptions about eight other issues for their
infants who had been hospitalized in an NICU. RESULTS: Parents reported
approximately 62% of the medical diagnoses for their infants during NICU
hospitalization; these significantly differed from hospital-chart diagnoses.
Parents who reported current or future effects of neonatal diagnoses also (a) had
fears for their infants while in the hospital or currently, (b) perceived
prematurity as having current or future effects, (c) reported restrictions for
their infants caused by neonatal diagnoses, and (d) gave less optimal ratings for
their infants' current health status. Parents' perceptions of current or future
effects of neonatal diagnoses appeared to be inaccurate given the actual
diagnoses for their infants. DISCUSSION: The underreporting of diagnoses by
parents raises several issues as to how accurately parents are perceiving their
infants. Parents who perceived continued effects of neonatal diagnoses also had
less optimal perceptions of other related issues. Parent's perceptions of
continued effects of neonatal diagnoses appeared to be unwarranted with respect
to the actual diagnoses assigned to their infants.
PMID- 9652280
TI - Creating spaces that enhance nurse practitioner practice.
AB - STUDY QUESTION: What barriers related to limitations of space or facilities do
nurse practitioners (NPs) describe in association with their current practice?
METHOD: This was a descriptive quantitative/qualitative study of 81 NPs in one
Midwestern state with a survey instrument previously developed under the auspices
of the Division of Nursing and the American Association of Colleges of Nursing
regarding advanced practice nursing. RESULTS: Of 641 questionnaires mailed to the
total number of prescribing NPs in the state, 372 (58%) were returned. Of that
number, 81 (22%) indicated that space limitations were a barrier to practice.
Seven themes emerged in qualitative analysis of their narrative descriptions of
this barrier. DISCUSSION: Results of this study can assist NPs to articulate
their space requirements and enhance existing spaces to better meet patient and
NP needs.
PMID- 9652281
TI - Child passenger safety.
AB - Motor vehicle crashes are a leading cause of death and disability among children
in the United States despite the fact that child safety seats and seat belts can
provide effective protection against serious and fatal injuries. Many child car
seats and safety restraints are being used incorrectly. In addition, recent
fatalities associated with children and air bags have heightened awareness of
child passenger safety issues. Pediatric nurse practitioners are in an excellent
position to offer motor vehicle occupant prevention strategies to families
through health education and anticipatory guidance.
PMID- 9652282
TI - Parent's behaviors, knowledge, and beliefs related to unintentional firearm
injuries among children and youth in the southwest.
AB - INTRODUCTION: The purpose of this research study was to describe parents'
behaviors, knowledge, and beliefs related to unintentional firearm injuries among
children and youth. METHOD: A convenience sample of 80 parents whose children
were attending one of six Kindercare Learning Centers in a Southwestern city was
surveyed during the summer of 1995 to learn about their behaviors, knowledge and
beliefs about unintentional firearm injuries among children and youth. Data on
demographic characteristics, behaviors, knowledge, and beliefs, were collected
with a questionnaire. RESULTS: Men and parents who had grown up with a gun in the
house were more likely to be gun owners. Forty-eight percent of parents kept at
least one gun in the home. Twenty-six percent of gun owners reported that the gun
was loaded at all times, and 18% reported that a gun was kept within reach of a
child. The most common reason given by parents for having a gun was for
protection (61%). Only 8% of parents reported having discussed firearm safety
with a health care worker. None of the parents had discussed firearm safety with
a pediatrician. A test of knowledge about firearm injuries revealed some gaps in
knowledge, with no significant differences between men and women or gun owners
and non-gun owners. DISCUSSION: Results suggest that firearms in the home
continue to pose a significant risk to children. Anticipatory guidance from NPs
and pediatricians is needed to protect children from unintentional firearm
injuries.
PMID- 9652283
TI - Risky choices: the dangers of teens using self-induced abortion attempts.
AB - Although researchers and practitioners alike have long been aware of the
existence and dangers of self-induced abortions, virtually no research exists on
this topic. This article describes methods of self-induced abortion from current
and historical literature. A case study of an adolescent using quinine is
discussed to highlight both the reasons some adolescents choose to self-abort and
the possible dangers of using such methods. Serious risks to the adolescent are
associated with any self-induced abortion attempt. Nurse practitioners are in a
key position to assess an adolescent's risk factors for self-induced abortion
attempts and to educate about the dangers of such attempts.
PMID- 9652284
TI - Update on feeding babies solid food.
PMID- 9652285
TI - Rewards.
PMID- 9652286
TI - Acute abdominal pain: a challenge for the practitioner.
PMID- 9652287
TI - Adolescent injury prevention.
PMID- 9652288
TI - Hot issues for NPs in 1998.
AB - Although it is unlikely that the legislative endeavors of 1996 and 1997 relating
to the health care industry will be matched in 1998, implementing regulations of
the Balanced Budget Act and the Health Insurance Portability and Accountability
Act will predicate the successes or shortcomings of these new laws in 1998. It is
important that NPs stay in close contact with their state legislators and
Medicaid officers responsible for implementing the SCHIP. NPs should also closely
track efforts at the Federal level to ensure inclusion of non-physician providers
in legislation that is important to NPs, such as bans on "gag" clauses--a
protection that should include all health care providers.
PMID- 9652289
TI - The score on high-tech sports nutrition for adolescents.
PMID- 9652290
TI - The stage is set for disease management and ESRD: can it succeed?
PMID- 9652291
TI - How hospitals can adapt to managing ESRD patient care.
PMID- 9652292
TI - Competing in the ESRD marketplace.
PMID- 9652293
TI - A case rating approach to improving clinical outcomes in ESRD.
PMID- 9652294
TI - A nephrologist's perspective. The Illinois Nephrology Alliance.
PMID- 9652295
TI - A consultant's perspective. Renal care of Louisiana.
AB - Much has been said regarding the evolution of managed care and what the ultimate
impact of managed care will have on the renal industry. The members of NIPA,
under the guidance of its Board of Directors, formed RenalCare of Louisiana in
order that the nephrologists could take the lead in defining and monitoring the
quality of care delivered to ESRD and pre-ESRD patients under an at-risk payment
methodology. NIPA places its members in the "drivers seat" in the development and
implementation of a renal disease management organization, and therefore, the re
engineering of the renal delivery system in Louisiana will be headed by Louisiana
nephrologists rather than for-profit dialysis chains.
PMID- 9652296
TI - Assessing the value of blood volume monitoring to improve outcomes. A comparative
observational study.
PMID- 9652297
TI - Disease management of ESRD: a brave new world for product suppliers.
PMID- 9652298
TI - HMOs and ESRD: a gloomy scenario.
PMID- 9652299
TI - Inadequate funding from payers will doom ESRD capitation.
PMID- 9652300
TI - Molecular and immunological characteristics of latex allergens.
AB - Natural rubber latex proteins are a well-recognized cause of type-I allergic
reactions that increasingly afflict health-care workers, housekeeping personnel,
and other persons using latex gloves or latex products. More than a dozen
individual latex allergens have been identified of which eight have received an
international nomenclature designation. To study the biochemical and
immunological properties in detail, it is desirable to clone and express each of
these allergens. Proteins that are involved in rubber synthesis are most likely
confined to latex whereas other enzymes, such as chitinases or glucanases, are
also present in fruits and may account for the symptoms observed in the latex
fruit syndrome. The available data on the molecular characterization of latex
allergens presented here illustrate the importance of this research in the
production of better diagnostic tests and, perhaps, tools for immunotherapy.
PMID- 9652301
TI - Induction of tolerance via the respiratory mucosa.
AB - Immunological tolerance is defined as a state of specific non-responsiveness to a
particular antigen induced by previous exposure to that same antigen. The mucosal
surfaces comprise the upper and lower respiratory tracts, the gastrointestinal
tract and the urogenitary tract, and are a major site of antigenic challenge. The
immune system associated with the mucosa has the extraordinary potential to
discriminate between antigens that are harmless (e.g. inhaled and dietary
antigens) and those that are associated with pathogens. Normally soluble proteins
delivered through the mucosal surfaces do not elicit a strong systemic immune
response but instead induce a transient local immune response that is replaced by
long-term peripheral unresponsiveness this is termed mucosal tolerance. The
phenomenon of oral tolerance is well established and considerable attention has
focussed on defining the underlying mechanisms. However, only comparatively
recently was the induction of tolerance via the respiratory mucosa described, and
it is this form of mucosal tolerance which forms the basis of this review.
PMID- 9652303
TI - Changes in blood leukocyte distribution during double-blind, placebo-controlled
food challenges in children with atopic dermatitis and suspected food allergy.
AB - BACKGROUND: The development of clinical reactions to food antigens is associated
with cellular changes. The aim of this study was to determine whether the
clinical outcome of double-blind, placebo-controlled food challenges would
correlate with changes in blood leukocyte distribution. METHODS: Double-blind,
placebo-controlled food challenges were performed in 17 children with atopic
dermatitis sensitized to hen's egg or cow's milk and in 9 children with atopic
dermatitis but not sensitized to food. Blood leukocyte distribution and
lymphocyte subsets were determined prior to and 24 h after challenges. RESULTS:
In food-sensitized children the numbers of leukocytes and lymphocytes decreased
significantly after allergen challenge independent of the clinical outcome of the
provocation (p < 0.002 in both cases). This decrease was seen in T (CD3+) and B
(CD19+) cell subsets (p<0.007 and p<0.0005, respectively). The CD4/CD8 ratio
increased (p<0.04). The number of memory cells (CD45R0) dropped (p<0.02 for CD4
and p<0.004 for CD8) and there was a loss of L-selectin (p<0.003 for CD4 and
CD8). No changes in thrombocytes, neutrophils, eosinophils and basophils were
observed. None of these changes were seen in the sensitized patients during
placebo challenges or in the non-sensitized group of children. CONCLUSION:
Changes in the leukocyte distribution after allergen challenge seem to be
associated with sensitization, but not with the clinical outcome of the oral food
challenge. They reflect important changes in the immune system in response to
allergens, but are not useful in monitoring double-blind, placebo-controlled food
challenges.
PMID- 9652302
TI - Bell peppers (Capsicum annuum) express allergens (profilin, pathogenesis-related
protein P23 and Bet v 1) depending on the horticultural strain.
AB - BACKGROUND: Little is known about the role of bell peppers in food allergy. We
collected sera from 11 patients with food allergy to bell peppers to analyze bell
pepper extracts for allergen composition. METHODS: Proteins of mature fruits of
eight horticultural strains of bell peppers were extracted and tested with
patients' sera for IgE binding and with monoclonal and polyclonal antibodies in
immunoblot. RESULTS: Profilin was detected in bell pepper extracts by an anti
celery profilin antibody. It showed high IgE binding activity in all extracts,
which could be inhibited by recombinant birch pollen profilin. Anti-birch pollen
monoclonal antibody BIP3, directed against birch pollen proteins between 30 and
69 kD, bound to bell pepper antigens of comparable molecular weights. A homologue
of the major birch pollen allergen Bet v 1 was detected in four of eight
horticultural strains of bell peppers, and was shown to bind IgE in 1 of the 11
patients. A 23-kD allergen of bell peppers was shown to correspond to the 23-kD
major paprika allergen by IgE absorption experiments. Its N-terminal sequence
showed 100% identity to P23 from tomatoes. CONCLUSION: The appearance of profilin
in all and Bet v 1 in 50% of the tested horticultural strains indicates that bell
peppers have to be considered potentially dangerous for Bet v 1- and profilin
sensitized patients. Moreover, in 4 of 8 horticultural strains of bell peppers a
homologue of the osmotin-like protein P23 from tomatoes is responsible for
substantial IgE binding. Contact with Bet v 1 and P23 homologues in bell peppers
can therefore be minimized by avoidance of the respective horticultural strains.
PMID- 9652304
TI - Cytokine production by CD4+ and CD8+ T cells in mice following primary exposure
to chemical allergens: evidence for functional differentiation of T lymphocytes
in vivo.
AB - It has been demonstrated previously that repeated exposure of mice to chemical
allergens of different types results in the development of qualitatively
divergent immune responses characterized by the production by draining lymph node
cells (LNC) of distinct cytokine patterns. Chronic exposure of mice to contact
allergens, such as 2,4-dinitrochlorobenzene (DNCB), resulted in the secretion by
LNC of low or undetectable levels of interleukins 4 and 10 (IL-4 and IL-10), but
comparatively high levels of interferon gamma (IFN-gamma); the latter cytokine
being produced by both CD4+ and CD8+ cells. In contrast, chronic exposure of mice
to trimellitic anhydride (TMA), a respiratory allergen associated in humans with
occupational asthma, induced instead the production by LNC of relatively high
concentrations of IL-4 and IL-10, but little IFN-gamma. The low levels of IFN
gamma secretion which were provoked by treatment with TMA were shown to derive
from CD8+ cells exclusively. In the present investigations we have sought to
determine whether the polarized responses observed following repeated exposure to
these chemical allergens are reflected by cytokine secretion patterns provoked by
primary exposure. To this end, mice of BALB/c strain were exposed epicutaneously
daily for 3 consecutive days to concentrations of DNCB and TMA (1 and 10%,
respectively), or to oxazolone, another contact allergen (0.25%), that resulted
in substantial proliferative activity in draining lymph nodes. The production by
draining LNC of IFN-gamma and of mitogen-inducible IL-4 was measured by enzyme
linked immunosorbent assay and the relative contribution of CD4+ and CD8+ cells
to the patterns of cytokine secretion observed was analyzed using both positive
and negative selection methods. It was found that primary exposure to DNCB,
oxazolone and TMA each resulted in the production by LNC of both IFN-gamma and IL
4. Selective depletion of, or enrichment for, CD4+ and CD8+ cells revealed that
only CD4+ cells elaborated mitogen-inducible IL-4. Depletion of neither CD4+ nor
CD8+ cells compromised the production by TMA- or DNCB-activated LNC of IFN-gamma,
although positively selected CD8+ cells were considerably less able than CD4+
cells to elaborate this cytokine, presumably secondary to a lack of appropriate
accessory cells. Taken together the results demonstrate that early during immune
responses to DNCB or oxazolone and TMA there is no evidence for the selectivity
of cytokine secretion patterns that characterizes responses following more
chronic exposure. Moreover, it is clear that exposure to TMA initially induces
the production of IFN-gamma by both CD4+ and CD8+ cells, whereas after more
chronic treatment the secretion of this cytokine is a function of CD8+ cells
exclusively. Collectively, these results indicate that the polarized responses
that develop in mice following chronic exposure to different classes of chemical
allergen are not reflected by the characteristics of primary immune responses. As
such the development of qualitatively divergent immune responses to chemical
allergens provides a paradigm for the evolution of differentiated T cell function
with time and/or with antigen exposure.
PMID- 9652305
TI - Diesel exhaust inhalation enhances airway hyperresponsiveness in mice.
AB - BACKGROUND: Repeated intratracheal instillation of diesel exhaust particles and
ovalbumin-induced airway hyperresponsiveness and airway inflammation in mice.
However, the effects of daily inhalation of diesel exhaust may differ from the
effects of direct instillation. METHODS: Therefore, mice were exposed to diesel
exhaust by inhalation 12 h per day for 3 months. Before the diesel exhaust
exposure, ovalbumin was injected intraperitoneally as a sensitization. After 3
weeks of diesel exhaust exposure, these mice were challenged with ovalbumin every
3 week thereafter. RESULTS: Diesel exhaust exposure with antigen challenge
induced airway hyperresponsiveness and airway inflammation which was
characterized by increased numbers of eosinophils and mast cells in lung tissue.
The recruitment of inflammatory cells was accompanied by an increment in goblet
cells on bronchial epithelium. Diesel exhaust exposure alone also enhanced airway
hyperresponsiveness, but did not induce eosinophilic infiltration and/or an
increment in goblet cells. CONCLUSION: Diesel exhaust inhalation enhanced airway
hyperresponsiveness and airway inflammation caused by ovalbumin sensitization in
mice.
PMID- 9652306
TI - Contractile responses to allergen and cholinergic stimulation in bronchus and
trachea of cockroach allergen-sensitized guinea pigs.
AB - Airway hyperreactivity is a hallmark of asthma. Yet, the role of allergic
sensitization in the hyperreactivity remains controversial. This study examined
the effects of airborne cockroach allergen (CRa) sensitization on the
contractility of bronchial (BSM) and tracheal (TSM) smooth muscle rings to
cholinergic stimulations, and to specific antigen, in vitro. Guinea pigs were
actively immunized with CRa, 5 mg (high dose, HD), 0.5 mg (low dose, LD), or
saline aerosols (2x/day, 5 days/week, for 4 weeks) and challenged by CRa
inhalation 5 days after last exposure. Twenty-four hours postchallenge, the
contractions of the TSM and BSM to electrical field stimulation (EFS),
acetylcholine (ACh), and to CRa were measured in vitro. In addition, the
contraction to these stimuli were also examined in the passively sensitized TSM
with the sera of CRa-immunized guinea pigs. The contractile responses of actively
immunized and passively sensitized tissues to EFS and ACh were very similar to
those of control tissues. CRa induced dose-dependent contractions in both
actively immunized and passively sensitized, but not in control, tissues. The CRa
induced contraction was stronger in the HD group than in the LD group (p<0.0001).
Leukotriene C4/D4 receptor antagonist LY-171883 inhibited the CRa-induced
contraction by 86% in actively immunized TSM, and by 9% in the passively
sensitized TSM. Pyrilamine inhibited the contraction by 57% in actively immunized
TSM and 70% in passively sensitized TSM. The results indicate that CRa
sensitization does not cause increased airway smooth muscle contractility to
cholinergic stimulations, but induces antigen-specific contractions in vitro.
Leukotrienes appear to play a significant role in the CRa-specific contractions,
more in the actively immunized than those in the passively sensitized tissues,
while histamine exerts a moderate effect on the CRa-induced contractions.
PMID- 9652307
TI - Inhibitory effects of lodoxamide on eosinophil activation.
AB - Recent reports describe the beneficial use of lodoxamide, an anti-allergic
compound, for the treatment of asthma and allergic conjunctivitis. Lodoxamide is
known as a mast cell stabilizer, however, the association of a significant
clinical improvement with a specific decrease in eosinophil infiltrate suggested
possible direct effects of lodoxamide on eosinophils. The chemotactic response of
eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose
dependently inhibited by Lodoxamide. Lodoxamide was also able to strongly inhibit
the release of eosinophil peroxidase after IgA-dependent activation and, to a
lesser extent, the release of eosinophil cationic protein and eosinophil-derived
neurotoxin. Moreover, the release of cytotoxic mediators evaluated in an antibody
dependent cytotoxicity assay against parasitic targets was also significantly
reduced, not only in the case of human eosinophils but also in a rat eosinophil
mast cell model of cytotoxicity. Taken together, these results indicate that
lodoxamide can exert potent inhibitory effects on eosinophil activation in vitro
combined with a strong inhibition of eosinophil attraction, leading therefore to
a reduction in their pathological potential in vivo.
PMID- 9652308
TI - Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A
activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor
antagonist SR 48692.
AB - BACKGROUND: Neurotensin (NT), a peptide found in brain and several peripheral
tissues, is a potent stimulus for mast cell secretion and its actions are blocked
by the specific NT receptor antagonist, SR 48692. Subsequent to stimulation, NT
is rapidly degraded by mast cell carboxypeptidase A (CPA). In the experiments
described here, we tested for the involvement of CPA activity in the activation
of mast cell secretion by the peptide, NT. METHODS: Mast cells were isolated from
the peritoneal and pleural cavities of rats, purified over metrizamide gradients
and incubated at 37 degrees C in Locke solution or Locke containing the
appropriate inhibitors. For some experiments, media derived from mast cells
stimulated by compound 48/80 were used as a source of mast cell CPA activity.
RESULTS: Treatment of mast cells with the highly specific peptide inhibitor of
CPA derived from potato (PCI) inhibited histamine release in response to NT and
NT8-13 (the biologically active region of NT). This inhibition required some 20
min to develop and was only partially reversed by a 20-min wash period. PCI (10
microM) did not inhibit histamine release in response to NT1-12, bradykinin,
compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also
inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the
brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast
cell CPA activity as well as bovine pancreatic CPA activity in a concentration
dependent manner. DISCUSSION: It is suggested that the mast cell binding site for
NT and the active site for CPA may share similar characteristics. The results are
discussed in terms of NT mechanism of action on the mast cell.
PMID- 9652309
TI - Role of CD4+ and CD8+ T cells in regulating the chronic development of liver
injury induced by delayed-type hypersensitivity to picryl chloride.
AB - In this study we first investigated the cellular immune responses in mice with
chronic liver injury induced by delayed-type hypersensitivity to picryl chloride
(PCl). A continuous reduction, after week 3 of liver injury, was observed in the
level of PCl-induced contact sensitivity but not in sheep red blood cell-induced
footpad reaction, suggesting the presence of PCl-specific suppression. When
spleen cells from mice whose liver had been injured for 1 week were systemically
transferred into syngeneic recipients with the liver injury, the elevation in
serum lactic dehydrogenase and the decrease in alkaline phosphatase and albumin
levels in recipient mice were significantly exacerbated. However, when the liver
damage in the donor mouse was allowed to proceed for 3, 5 or 7 weeks, biochemical
changes in recipients were reduced to near normal levels. A flow-cytometric assay
demonstrated that the number of CD4+ T cells in both spleen cells and liver
nonparenchymal cells decreased dramatically during the late phase of liver
injury, while CD8+ counts did not. These findings suggest that CD4+ and CD8+ T
lymphocytes may contribute to the positive and negative regulation, respectively,
of the early and late phases in the chronic development of liver injury.
PMID- 9652310
TI - Seasonal chronic cough with sputum eosinophilia caused by Trichosporon cutaneum
(Trichosporon asahii).
AB - The case of a 46-year-old man with a chronic cough with sputum eosinophilia
(atopic cough) caused by Trichosporon cutaneum serotype II (Trichosporon asahii)
is reported. The diagnosis was made with the inhalation challenge test with T.
asahii antigen. He was admitted for the diagnosis and treatment of a severe
nonproductive cough in the summer season. Although his sputum contained 13%
eosinophils of nucleated cells, he did not have bronchial hyperresponsiveness to
methacholine or a heightened bronchomotor tone. Bronchodilator therapy was not
effective for his cough. His symptoms worsened on returning home, suggesting the
existence of some etiologic agent in his house. A high titer of serum anti
Trichosporon antibody was detected and antigen provocation test with the
Trichosporon extract was positive: the development of a cough 6 h later and a
decrease in the cough threshold to inhaled capsaicin 48 h later (7.85 microM from
31.3 microM prechallenge). This is the first report on a chronic cough with
sputum eosinophilia induced by T. cutaneum (T. asahii).
PMID- 9652311
TI - Mast cell, IgE and atherothrombosis.
PMID- 9652312
TI - Echocardiographic assessment of right atrial function in patients with myocardial
infarction with reference to obstructive lesions of the coronary arteries.
AB - We assessed the relationship between right atrial (RA) function and obstructive
lesions of the coronary arteries in 29 patients with recent or old myocardial
infarction (MI). Patients were divided into 3 groups according to the location of
obstructions as follows: obstruction at the proximal right coronary artery
(segments 1 and 2) (RCA proximal group, n=9); obstruction at the distal RCA
(segments 3 and 4) (RCA distal group, n=6); and obstruction at the left anterior
descending coronary artery (LCA group, n=14). The RA volume and the fractional
change in the RA area during atrial contraction (RA %AC) were evaluated by apical
2-dimensional echocardiography. The right ventricular (RV) end-diastolic pressure
(RVEDP) was measured in 4 patients in the RCA proximal group and 4 patients in
the LCA group. The ejection fraction of the right ventricle (RVEF) was measured
by radionuclide angiography or 2-dimensional echocardiography in 7 patients in
the RCA proximal group, 5 patients in the RCA distal group, and 7 patients in the
LCA group. The RVEF tended to be lower in the RCA proximal group than in the RCA
distal and LCA groups. The RA volume was significantly greater in the RCA
proximal group than in the LCA group. The RA %AC was significantly smaller in the
RCA proximal group than in the RCA distal and LCA groups. There were no
significant differences in the early diastolic RV inflow velocity among groups,
but the late diastolic RV inflow velocity was significantly lower in the RCA
proximal group than in the RCA distal and LCA groups. There was no significant
difference in the RVEDP between the RCA proximal and LCA groups. Thus, RA
dysfunction in the RCA proximal group appeared to be due to myocardial damage
rather than to afterload mismatch. These findings suggest that RA dysfunction may
occur in patients with an inferior MI who have an obstructive lesion of the
proximal RCA.
PMID- 9652313
TI - The relation between the pacing sites in the right ventricular outflow tract and
QRS morphology in the 12-lead ECG.
AB - Optimal pace mapping is a good predictor of the appropriate ablation site for
idiopathic right ventricular tachycardia (VT) originating from the right
ventricular outflow tract (RVOT). We studied the relationship between the RVOT
pacing site and QRS morphology in the 12-lead ECG during pacing to find the
optimal site more quickly. In 13 patients with idiopathic VT, pacing at 8 sites
in the RVOT (free wall, septum, and anterior and posterior regions of upper and
lower sites) was performed while 12-lead ECGs were recorded. The R-wave amplitude
minus the S-wave amplitude in lead I (RI-SI) and aVF (RavF-SavF) and the
transitional zone index (TZI) were compared in the different pacing sites; TZI
was defined to examine the transitional zone as a value. The RI-SI was smaller in
the anterior region than in the other regions, and the negative RI-SI predicted
that the pacing site was in the upper or lower anterior regions. The RavF-SavF
was larger in the septum and anterior regions than in the free wall and posterior
regions. The TZI was larger in the free wall region than in the septum. From the
results, we constructed a flow chart that differentiates the origin of the
arrhythmia in the RVOT and a directional guide that indicates the direction from
the current mapping site for optimal pace mapping. The results provided an ECG
guide for locating the focus of VT originating from the RVOT. These findings may
systematically improve the mapping procedure.
PMID- 9652314
TI - Prognostic value of 1-day stress/rest electrocardiogram-gated single-photon
emission computed tomography using Tc-99m-labeled methoxy-isobutyl isonitrile.
AB - To evaluate the prognostic value of the simultaneous assessment of perfusion and
left ventricular wall motion, exercise non-gated/rest electrocardiogram (ECG)
gated 99mTc methoxy-isobutyl isonitrile (MIBI) single-photon emission computed
tomography (SPECT) was performed in 182 patients suspected of having coronary
artery disease. After injection of 250 MBq of 99mTc-MIBI at peak exercise, stress
perfusion images were classified into 3 groups: normal, equivocal, and abnormal.
Normal subjects completed the 1-day protocol but not the resting study, whereas
patients with abnormal or equivocal perfusion images underwent ECG-gated SPECT
study with injection of 750 MBq of 99mTc-MIBI 3 h later. Patients with normal
perfusion during this protocol had a benign prognosis. Only 4 soft events
occurred in the normal group (4.8%). In contrast, patients with both myocardial
infarction and abnormal wall motion at rest experienced more cardiac events (7
cardiac events including 1 cardiac death among a total of 45 patients; 15.6%,
p<0.05 compared with normal subjects). In addition, ischemic patients also
experienced more cardiac events (7 events including 2 cardiac deaths among a
total of 25 subjects; 28.0%, p<0.01 compared with normal patients). Our data
suggest that the simultaneous assessment of perfusion and wall motion by
stress/rest ECG-gated 99mTc-MIBI SPECT is a reliable indicator of prognosis in
patients suspected of having coronary artery disease.
PMID- 9652315
TI - A psychobehavioral factor, alexithymia, is related to coronary spasm.
AB - The aim of this study was to assess whether the psychobehavioral pattern
alexithymia is related to coronary artery spasm. Alexithymia, deficient
psychological awareness, was examined using the Minnesota Multiphasic Personality
Inventory Alexithymia Scale in 100 patients with angina pectoris in whom coronary
spasm, defined as > or = 99% coronary narrowing, was documented upon ergonovine
provocation, and in 109 patients with chest pain syndrome who were shown to have
almost normal coronaries without inducible coronary spasm on coronary angiogram
(control group). Alexithymia was approximately twice as prevalent in the coronary
spasm group (31%) as in the control group (14%) (p<0.01). Among various
conventional risk factors including hyperlipidemia, obesity, diabetes mellitus,
hypertension, hyperuricemia, or family history of ischemic heart disease, only
male sex and smoking were more prevalent in the coronary spasm group than in the
control group (p<0.001). The odds ratios of coronary spasm adjusted for all the
other risk parameters including sex and age were 4.14 [95% confidence interval
(CI) 1.81-9.47] for alexithymia and 2.38 (95, CI 1.18-4.82) for smoking. A
psychobehavioral pattern, alexithymia, relates to coronary spasm. This
relationship is independent of the conventional coronary risk factors.
PMID- 9652316
TI - Early mortality after acute myocardial infarction: observational study in
Yamagata, 1993-1995.
AB - Although considerable information is available regarding the prognosis after
acute myocardial infarction (AMI) in Western populations, little is known about
the fate of Japanese subjects after AMI. The purpose of this study was to assess
short-term mortality and factors influencing it after AMI in Japan. From April
1993 to December 1995, 1,014 patients with AMI from 41 hospitals in Yamagata
Prefecture were registered by cardiologists for the prospective survey. Among
patients who died within 28 days after the onset of AMI, immediate causes of
death were examined and the clinical profiles of these subjects were compared
with those of patients that survived. Early death occurred in 184 patients (short
term mortality 18%). Patients who died were significantly older than survivors
(76.1+/-9.4 vs 67.6+/-11.8 years, p<0.01). They were also more likely to be women
(50% vs 31%, p<0.01), to have had hypertension (64% vs 54%, p<0.05), diabetes
mellitus (29% vs 20%, p<0.02), prior MI (17% vs 12%, p<0.05), or Killip class III
or IV disease (63% vs 15%, p<0.01), and were significantly less likely to be
current smokers (26% vs 45%, p<0.01) or to have been treated with reperfusion
therapy (27% vs 63%, p<0.01). Multivariate logistic analysis demonstrated that
independent predictors of early death were Killip class III or IV and advanced
age. Reperfusion therapy was a negative predictor of death. Patients who died had
arrived at hospital earlier than patients who survived. Mortality as a result of
heart failure, cardiac rupture, or arrhythmia fell exponentially after the onset
of AMI. Thus, the predictors of short-term mortality were similar to those
reported in Western populations. More deaths occurred just after the onset of
disease, suggesting that early therapy is important in reducing short-term
mortality.
PMID- 9652317
TI - Circadian variation in plasma levels of free-form tissue factor pathway inhibitor
antigen in patients with coronary spastic angina.
AB - Tissue factor pathway inhibitor (TFPI) is known to inhibit the initial reaction
in the tissue factor-mediated coagulation pathway. We measured plasma free-form
TFPI antigen levels and monitored 24-h Holter recordings at 06.00, 14.00 and
22.00 h in 15 patients with coronary spastic angina, 13 patients with stable
exertional angina, and 11 control subjects. There was a significant circadian
variation in plasma free-form TFPI antigen levels in patients with coronary
spastic angina (25.8+/-2.0 ng/ml at 06.00 h, 21.1+/-1.6 ng/ml at 14.00 h, and
20.2+/-1.4 ng/ml at 22.00 h; p<0.01). Furthermore, free-form TFPI antigen levels
at 06.00 h were significantly higher in coronary spastic angina patients than in
patients with stable exertional angina or control subjects (p<0.01). Free-form
TFPI antigen levels increased after the ischemic attacks in coronary spastic
angina (p<0.01). This circadian variation correlated with the frequency of
attacks, with the peak level occurring between midnight to early morning in
patients with coronary spastic angina.
PMID- 9652318
TI - The correlation between coronary stenosis index and flow-mediated dilation of the
brachial artery.
AB - We examined the relationship between flow-mediated dilation (FMD) of the brachial
artery and the extent and severity of coronary artery disease (CAD). Using high
resolution ultrasonography, we measured FMD and nitroglycerin-induced brachial
artery dilation. We studied 121 patients (77 men, 44 women; mean age 64+/-11
years, range 25-79 years) who underwent coronary arteriography. The extent and
severity of CAD were assessed by the coronary stenosis index (CSI). The adjusted
FMD correlated inversely with CSI (rs=-0.63, p<0.0001). Multivariate analysis
demonstrated that the adjusted FMD was an independent predictor of CSI. The
adjusted FMD was 10.2+/-4.8% in patients without CAD (n=32), 7.7+/-6.0% in
patients with single-vessel disease (n=31), 5.2+/-5.5% in patients with double
vessel disease (n=29), and 2.0+/-3.9% in patients with triple-vessel disease
(n=29). The adjusted FMD was significantly lower in the double- (p<0.01) and
triple-vessel (p<0.0001) disease groups than in patients without CAD. The
adjusted FMD was significantly lower in the triple-vessel disease group than in
the single-vessel disease group (p<0.001). Based on our results, as coronary
atherosclerosis becomes more severe, the adjusted brachial artery FMD becomes
more severely impaired.
PMID- 9652319
TI - Validity of a self-administered diet history questionnaire for assessment of
sodium and potassium: comparison with single 24-hour urinary excretion.
AB - We developed a self-administered diet history questionnaire (DHQ) for use in
prevention and control of cardiovascular diseases and cancer, and validated it by
comparison with single 24-h urinary excretion of sodium (Na) and potassium (K).
The subjects were 154 male and 69 female freshmen university students. Mean
intakes (mmol/day) assessed by DHQ and the urinary excretion of Na were 196 and
165 respectively for men and 179 and 136 respectively for women. Those of K were
61.5 and 43.9 respectively for men and 56.8 and 41.6 respectively for women. The
ratios of urinary excretion to dietary intake of Na were 0.97 in men and 0.84 in
women. Those of K were 0.78 in men and 0.80 in women. The results for both Na and
K were reasonable, except for Na in men. When Pearson correlation was examined
between dietary and urinary Na and K, no significant correlations for Na in men
(r=0.14) or women (r=0.23, p=0.06), or significant correlations for K in men
(r=0.34, p<0.001) or women (r=0.40, p<0.001) were observed. The results suggest a
reasonable ability to estimate a subject mean for Na in women, K in both sexes,
and individual level for K for both sexes. The validity for individual level for
Na intake is not conclusive because the duration of urine collection was too
short.
PMID- 9652320
TI - Doppler echocardiographic assessment and cardiac gene expression analysis of the
left ventricle in myocardial infarcted rats.
AB - The purpose of this study was to examine cardiac geometry and function by Doppler
echocardiography and to analyze mRNA expression of cardiac phenotype and
extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and
hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels
in the non-infarcted left ventricle (LV) and infarct site were measured by
Northern blot analysis. LV internal diastolic dimension was greater in infarcted
(MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm,
p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/
3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec
vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling
wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7
m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control
35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early
filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels
for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic
polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP
2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1
(all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated
myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)
beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0
, 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated
myocardium. Myocardial infarcted rat was characterized by cavity dilation and
marked abnormalities of systolic and diastolic function, accompanied by a shift
of myocytes to fetal phenotype and activation of collagen genes in the non
infarcted myocardium.
PMID- 9652322
TI - Alterations in sarcoplasmic reticulum and angiotensin II type 1 receptor gene
expression after myocardial infarction in rats.
AB - The purpose of this study was to investigate the function of sarcoplasmic
reticulum (SR) and the role of angiotensin II type 1 receptor (AT1) in
ventricular remodeling in non-infarcted areas after myocardial infarction (MI).
MI was produced in anesthetized Sprague-Dawley rats (10-12-weeks old) by ligation
of the left anterior descending coronary artery. Four weeks after MI, hemodynamic
measurements were performed. SR Ca2+-ATPase activity and mRNA (SERCA2a) and AT1
mRNA (AT1a, AT1b) were analyzed. Left ventricular end-diastolic pressure was
higher and left ventricular dp/dt was significantly lower in the MI group. In non
infarcted areas in the MI group, myocardial transverse diameter was significantly
greater and both Ca2+-ATPase activity in the SR and SERCA2a level decreased. The
AT1a level was higher in non-infarcted areas than in controls, whereas the AT1b
mRNA expression level was unchanged. These results suggest that, in the
ventricular remodeling after MI, alterations in SR protein and its mRNA in non
infarcted myocardium help initiate heart failure and that Ca overload caused by
the up-regulation of AT1a mRNA is an important cause of alteration in SR
function.
PMID- 9652321
TI - Postrest shortening of the action potential duration in rabbits: in vitro and in
vivo correlation.
AB - Previous evidence has shown that the action potential duration of rabbit
ventricular muscle cells shortens after a rest period (postrest shortening).
However, there has not been much research on postrest shortening in the intact
heart. We recorded transmembrane action potentials (TAPs) of isolated papillary
muscle from rabbit ventricle with glass microelectrodes and monophasic action
potentials (MAPs) of the rabbit left ventricular endocardium with contact
electrodes. In the in vitro experiments, repetitive regular stimuli (S1) at a
cycle length of 1 sec were followed by a single extrastimulus (S2) at coupling
intervals (S1S2) ranging between 0.5 sec and 8 sec. The increase in the S1S2
interval resulted in a progressive shortening of the duration of TAP elicited by
the S2, which was abolished by the simultaneous application of 1 mmol/L 4
aminopyridine and 2 micromol/L ryanodine. In the in vivo experiments, regular
right ventricular pacing (S1) at a cycle length of 0.35 sec was followed by a
single extrastimulus (S2) with coupling intervals (S1S2) ranging between 0.25 sec
and 3 sec. The increase in the S1S2 interval also resulted in a progressive
shortening of the duration of MAP elicited by the S2. This is the first report to
demonstrate postrest shortening in the intact heart, which probably occurs
because of a mechanism analogous to that observed in the isolated ventricular
muscle.
PMID- 9652323
TI - Coronary-pulmonary artery fistulae depicted by multiplanar reconstruction using
magnetic resonance imaging.
AB - We compared the imaging capability of magnetic resonance angiography (MRA) with
that of conventional coronary angiography in a patient with coronary-pulmonary
fistulae. Using the latter procedure, it is difficult to measure abnormal
tortuous blood vessels in one section. However, the course of blood vessels could
be evaluated quite well by rearranging serial cross-sectional MRA images using
multiplanar reconstruction (MPR). This procedure allowed us to determine the
anatomic positional relationship of these vessels to the peripheral cardiac great
vascular system. MPR may detect sites of influx and outflow of abnormal blood
vessels.
PMID- 9652324
TI - A case of cardiac sarcoidosis: significance of ventricular tachycardia
originating from the septum.
AB - A 65-year-old woman was admitted for assessment of recurrent tachycardia. Cross
sectional echocardiography showed that the anterobasal portion of the ventricular
septum was thin and dyskinetic. An electrophysiologic study revealed ventricular
tachycardia, during which marked fragmented potentials could be obtained from the
anterior septal aspect of the right ventricle. The site of earliest activation
was in the vicinity of the His bundle. A diagnosis of cardiac sarcoidosis was
made by based on endomyocardial biopsy combined with the clinical manifestations.
Ventricular tachycardia originating from the anterior septum may be an indicator
of underlying cardiac sarcoidosis.
PMID- 9652325
TI - Use of temporary vena cava filters after catheter-directed fragmentation and
thrombolysis in patients with acute pulmonary thromboembolism.
AB - Acute pulmonary thromboembolism is a life-threatening disease and in almost all
cases originates from deep venous thrombosis in the proximal deep venous system
of the legs. In order to prevent further episodes of thromboembolism in 2
patients with acute pulmonary thromboembolism, we inserted an Antheor temporary
vena cava filter after catheter-directed fragmentation and thrombolysis. No
complications occurred during the insertion of the filters and our results
suggest that this filter device may be clinically safe and effective for
temporary protection against pulmonary thromboembolism.
PMID- 9652326
TI - Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of
radionuclide imaging for differential diagnosis.
AB - A 62-year-old woman with skin sarcoidosis was admitted to our hospital to
ascertain whether she had cardiac involvement. Although she displayed no cardiac
signs or symptoms, the electrocardiogram showed first-degree atrioventricular
block, right bundle branch block with left anterior fascicular block, and giant
negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy
localized in the basal portion of the interventricular septum (IVS) without
systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise
thallium-201 myocardial imaging revealed redistribution in the anteroseptal
region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP)
scintigraphy revealed abnormal uptake in the myocardium. These findings
disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis
mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is
an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP
scintigraphy were useful and necessary to differentiate this type of cardiac
sarcoidosis from HCM.
PMID- 9652327
TI - Preload and incident angle independent index of left ventricular contractility
determined by continuous wave Doppler echocardiography.
AB - Although left ventricular dP/dtmax can be accurately assessed using Doppler
echocardiography, the fact that Doppler-derived dP/dtmax depends both on preload
and Doppler incident angle limits its clinical value. We investigated the
clinical usefulness of Doppler-derived (dP/dtmax)/IP (IP, isovolumic pressure),
which is known to be relatively insensitive to preload and theoretically
independent of the incident angle in 9 subjects. We conclude that Doppler-derived
(dP/dtmax)/IP is relatively insensitive to both the incident angle and preload.
In addition to its noninvasiveness, these unique features makes it very
attractive as a clinical index of ventricular contractility.
PMID- 9652328
TI - Birth insult alters ethanol preference in the adult rat.
AB - While genetic factors clearly play a role in regulating ethanol intake, the
present study considered the possibility that early environmental factors which
influence central nervous system development and long-term function might also
alter ethanol intake. The specific aim of the study was to test whether
alterations in birth condition, namely Caesarean section (C-section) birth and C
section birth with an added period of global anoxia, can affect subsequent
ethanol preference in the adult rat. At 5 months of age, groups of experimental
and vaginally born control rats were offered free choice between drinking water
or various concentrations of ethanol (1-10% v/v) in water across 36 days of
testing. Rats that had been born by C-section with 10 or 15 min of added global
anoxia showed significant reductions in ethanol preference scores, in comparison
to vaginally born controls. For the 10-min anoxia group, ethanol intake was
decreased, water intake was increased and total fluid intake remained unchanged
relative to values for vaginally born controls, across the entire test period.
Although total fluid intake by the 15-min anoxia group also did not differ from
that of vaginally born controls, the decreased ethanol preference scores in the
15-min anoxia group were mainly due to increased water intake during some test
periods and a combination of reduced ethanol intake and increased water intake
during others. Animals born by rapid C-section alone, with no added period of
global anoxia, showed reduced ethanol preference only during a few early periods
of testing, a much less pronounced effect than that observed for animals with
added global anoxia. When animals were given the choice between drinking water
vs. solutions of sucrose or NaCl, no group differences due to birth condition
were found on measures of sucrose or NaCl preference. Together with reduced
ethanol preference, the 10-min anoxia group showed a transient depression of
locomotor activity in response to a low dose (0.25 g/kg) of intraperitoneal
ethanol, which had no effect on locomotion in vaginally born controls. These
results indicate that a relatively subtle alteration in birth condition,
compatible with grossly normal development and behavior, is sufficient to alter
ethanol preference in the adult rat.
PMID- 9652329
TI - Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus
coeruleus.
AB - These experiments tested the hypothesis that substance P neurotransmission at
tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced
activation of the locus coeruleus, using c-fos as an index of activation.
Selective tachykinin NK1 receptor antagonists administered systemically did not
result in substantial locus coeruleus c-fos expression. Restraint stress resulted
in a large number of locus coeruleus c-fos expressing cells. Administration of
two selective tachykinin NK1 receptor antagonists prior to restraint resulted in
an increase in the number of locus coeruleus c-fos expressing cells, compared to
restraint alone. These results suggest that the enhanced c-fos expression
observed in response to tachykinin NK1 receptor antagonists combined with stress,
could be due to the blockade of tachykinin NK1 receptor-mediated activity at
sites other than the locus coeruleus, resulting in an overall activation of the
locus coeruleus.
PMID- 9652330
TI - Effects of yohimbine on naloxone-induced antinociception in a rat model of
inflammatory hyperalgesia.
AB - Effects of the alpha2-adrenoceptor antagonist yohimbine on the antinociception
produced by a low dose of naloxone were examined in a rat model of carrageenan
induced inflammation. In rats receiving saline prior to naloxone injection, the
low dose of naloxone (5 microg/kg, i.p.) significantly prolonged paw withdrawal
latency in response to noxious thermal stimuli for both the inflamed and the non
inflamed paws 4 h after carrageenan injection (6.0 mg in 0.15 ml saline). In rats
receiving yohimbine, the low dose of naloxone failed to produce prolongation of
paw withdrawal latencies 4 h after carrageenan, whereas naloxone produced
antinociception 7 days after carrageenan. The results suggest that noradrenergic
mechanisms are involved in naloxone-induced antinociception only in the early
phase of carrageenan-induced inflammation.
PMID- 9652331
TI - Tension generation and increase in voltage-activated Na+ current by crotamine.
AB - We performed the present experiments to study the action of crotamine, a toxin
isolated from the venom of the South American rattlesnake, Crotalus durissus
terrificus, on macroscopic Na+ currents in frog skeletal muscle by using the
loose patch clamp technique. Crotamine at 50 microM increased the peak Na+
current by 50% (P < 0.05). In addition, the voltage dependence of inactivation
was shifted by +8 mV. Other parameters of Na+ currents (reversal potential,
voltage-dependence of activation and time courses of inactivation, of activation
and of removal of inactivation) were not significantly affected. We suggest that
crotamine inhibits the direct transition of channels from closed to inactivated
states, thereby forcing their transition through the open states.
PMID- 9652332
TI - Bradykinin B2 receptors in nodose ganglia of rat and human.
AB - The present study has employed in vitro electrophysiology to characterise the
ability of bradykinin to depolarise the rat isolated nodose ganglion preparation,
containing the perikarya of vagal afferent neurons. Both bradykinin and kallidin
elicited a concentration-dependent (1-100 nM) depolarisation when applied to the
superfusate bathing the nodose ganglia, whereas the bradykinin B1 receptor
agonist, des-Arg9-bradykinin, was only effective in the micromolar range.
Furthermore, the electrophysiological response to bradykinin was antagonised by
the bradykinin B2 receptor antagonist, D-arginyl-L-arginyl-L-prolyl-trans-4
hydroxy-L-prolylglycyl-3-(2-t hienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3
isoquinolinecarbonyl+ ++-L-(2alpha,3beta,7abeta)-octahydro-1H-indole-2-carbonyl-L
arginine (Hoe 140), in a concentration-related manner. To determine the
anatomical location of functional bradykinin B2 receptors, in vitro
autoradiography with [125I]para-iodophenyl Hoe 140 was performed on sections of
rat and human inferior vagal (nodose) ganglia and confirmed the presence of
binding over vagal perikarya. Collectively, these data provide evidence for
functionally relevant bradykinin B2 receptors on vagal afferent neurons, which
are apparently also present on human vagal perikarya.
PMID- 9652333
TI - Effects of chylomicrons and chylomicron remnants on endothelium-dependent
relaxation of rat aorta.
AB - The effects of chylomicrons and chylomicron remnants on endothelium-dependent
relaxation of rat aorta were studied in vitro. Chylomicrons and chylomicron
remnants were prepared in vivo. Aortic rings were incubated with the lipoproteins
for 45 min before the vessels were constricted with phenylephrine and
concentration relaxation response curves constructed to carbachol, ATP, A23187
and S-nitroso-N-acetylpenicillamine. Maximum % relaxations to carbachol were
significantly reduced by both chylomicrons and chylomicron remnants but responses
to ATP and S-nitroso-N-acetylpenicillamine were unaffected. In addition,
chylomicrons significantly inhibited A23187-induced relaxation, causing an
increase in the EC50 value. Chylomicron remnants cause selective inhibition of
carbachol-induced relaxation suggesting an action at the receptor or G protein
coupled component of the receptor-mediated activation of the L-arginine-nitric
oxide pathway. Chylomicrons appear to be less selective in their inhibition of
the endothelium-dependent relaxation. This study demonstrates that lipoprotein
particles of dietary origin may cause endothelial cell dysfunction.
PMID- 9652334
TI - Central cardiovascular effects of tacrine in the conscious dog: a role for
catecholamines and vasopressin release.
AB - Centrally acting cholinergic agents are currently reported to increase blood
pressure in various species through the stimulation of muscarinic cholinoceptors.
Moreover, several cardiovascular adverse effects have been reported from clinical
studies. The aim of this study was to investigate the effects of tacrine, an
acetylcholinesterase inhibitor which has been reported to have therapeutic
potential in Alzheimer's disease, on blood pressure and two vasopressor systems
(sympathetic and vasopressinergic) in Beagle dogs. Intravenous (i.v.) tacrine (2
mg kg(-1)) induced, in conscious and anesthetized dogs, an increase in systolic
and diastolic blood pressure, accompanied by bradycardia. This increase was dose
dependent with a peak effect at 1.5 min following administration. Tacrine also
induced an increase in noradrenaline, adrenaline and vasopressin plasma levels.
Pretreatment with the muscarinic receptor antagonist, atropine (2 mg kg(-1),
i.v.), abolished the pressor response to i.v. injection of tacrine while
pretreatment with the peripheral muscarinic receptor antagonist,
methylscopolamine (0.2 mg kg(-1), i.v.), did not alter the increase in blood
pressure. Similarly, noradrenaline and adrenaline changes in plasma levels were
not modified by methylscopolamine but were abolished by atropine pretreatment. A
similar tendency although not significant was observed for vasopressin plasma
levels. The present results demonstrate that in dogs, tacrine (2 mg kg(-1), i.v.)
stimulates central muscarinic cholinoceptors to increase blood pressure through
activation of the two components of the sympathetic nervous system (i.e.,
neuroneuronal noradrenergic and the neurohormonal adrenergic pathways) as well as
through increasing noradrenaline, adrenaline and vasopressin plasma levels.
PMID- 9652335
TI - In vivo and in vitro action of endothelin-1 on goat cerebrovascular bed.
AB - This study concerned the effects and mechanisms of action of endothelin-1 on the
cerebral circulation. Cerebral blood flow was electromagnetically measured in
awake goats. Endothelin-1 (0.01-0.3 nmol) produced dose-dependent decreases in
this flow (maximal reduction = 34%) and increases in cerebrovascular resistance
(maximal increase = 74%) (P < 0.01). IRL 1620 (Suc-[Glu9, Ala11,15]endothelin-1
(8-21), agonist for endothelin ET(B) receptors, 0.01-0.3 nmol) slightly decreased
cerebral blood flow. The effects of endothelin-1, but not those of IRL 1620, on
cerebral blood flow were diminished by 50% during infusion of the antagonist for
endothelin ET(A) receptors, BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-Trp), 2 nmol min(
1)), but not affected during infusion of the antagonist for endothelin ET(B)
receptors, BQ-788 (N-[N-[N-[(2,6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-L
Leucyl-1-(met hoxycarbonyl)-D-tryptophyl]-Dnorleucine monosodium), 2 nmol min(
1)). Intravenous administration of NW-nitro-L-arginine methyl ester (L-NAME, 47
mg kg(-1)) or NW-nitro-L-arginine (L-NNA, 47 mg kg(-1)) reduced basal cerebral
blood flow by 39 and 33%, increased cerebrovascular resistance by 108 and 98% and
mean arterial pressure by 23 and 17%, and decreased heart rate by 27 and 25%,
respectively (all at least P < 0.05). The increases in cerebrovascular resistance
(as absolute values) induced by endothelin-1 were not affected during either L
NAME or L-NNA (as absolute values and percentages). Intravenous administration of
meclofenamate (5 mg kg(-1)) did not change the cerebrovascular effects of
endothelin-1 and IRL 1620. In isolated goat cerebral arteries under control,
resting conditions, endothelin-1 (10(-11)-10(-7) M) induced concentration
dependent contractions (EC50 = 4.78 X 10(-9) M; maximal contraction = 3177+/-129
mg), whereas IRL 1620 (10(-11)-10(-7) M) produced no effect. This contraction
produced by endothelin-1 was competitively blocked by BQ-123 (10(-7)-3 X 10(-6)
M), and was not affected by BQ-788 (10(-6) and 10(-5) M). L-NAME (10(-4) M),
meclofenamate (10(-5) M), indomethacin (10(-5) M), L-NAME (10(-4) M) plus
meclofenamate (10(-5) M) and phosphoramidon (10(-4) M) did not affect the
contraction in response to endothelin-1. Endothelium removal increased the
response to endothelin-1, as well as the BQ-123 antagonism against endothelin-1
(pA2 values, 7.62 vs. 6.88; P < 0.01). In both intact and de-endothelized
arteries precontracted with prostaglandin F2alpha endothelin-1 induced a further
contraction, and IRL 1620 caused no effect. These results suggest that: (1)
endothelin-1 produces cerebral vasoconstriction by activating endothelin ET(A)
receptors probably located in smooth muscle; (2) endothelin ET(B) receptors,
nitric oxide and prostanoids might be not involved in the cerebrovascular action
of endothelin-1, and (3) endothelium removal may increase cerebrovascular
reactivity by increasing sensitivity of endothelin ET(A) receptors to endothelin
1.
PMID- 9652336
TI - Cardiovascular effects of verapamil enantiomer combinations in conscious dogs.
AB - We examined the systemic and coronary hemodynamic effects of five combinations of
R- and S-verapamil enantiomers (R/S; 100/0, 90/10, 80/20, 50/50, and 20/80%,
respectively) in conscious dogs chronically instrumented for measurement of
aortic and LV pressure, +dP/dt, subendocardial segment length, coronary blood
flow velocity, and aortic blood flow. Dogs received escalating doses (0.1, 0.2,
and 0.4 mg kg(-1)) of each verapamil combination over 2 min at 30 min intervals
on different experimental days and peak changes in hemodynamics were recorded 2
min after each dose. All verapamil combinations increased heart rate, mean aortic
blood flow, and coronary blood flow velocity and decreased calculated systemic
and coronary vascular resistance. Alterations in coronary hemodynamics were most
pronounced with 20/80 R/S verapamil. Racemic and 20/80 R/S verapamil decreased
mean arterial and left ventricular systolic pressure, in contrast to combinations
with greater concentrations of the R enantiomer. Left ventricular function was
unchanged during administration of 100/0, 90/10, and 80/20 R/S verapamil. Direct
negative inotropic and lusitropic effects occurred with 50/50 and 20/80 R/S
verapamil. The high dose of 20/80 R/S verapamil also increased left ventricular
end-diastolic pressure and the regional chamber stiffness constant, consistent
with diastolic dysfunction. The results indicate that combinations of R- and S
verapamil produce differential hemodynamic and left ventricular functional
effects in conscious, unsedated dogs that are dependent on the relative ratio of
these enantiomers.
PMID- 9652337
TI - Influence of beta-adrenoceptor agonists on the pulmonary circulation. Effects of
a beta3-adrenoceptor antagonist, SR 59230A.
AB - The aims of this study were (a) to compare in the rat isolated perfused lung
preparation, the effects of isoprenaline and of three beta3-adrenoceptors
agonists, SR 59104A, (N-[(6hydroxy-1,2,3,4-tetrahydronaphtalen-(2 R)-2yl)methyl]
(2R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N[(7
methoxy-1,2,3,4-tetrahydronaphtalen-(2R)-2yl)methyl]-( 2R)-2-hydroxy-2-(3
chlorophenyl)ethanamine hydrochloride) and SR 58611A (ethyl?(7S)-7-[(2R)-2-(3
chlorophenyl)-2-hydroxyethylamino]-5,6,7, 8-tetrahydronaphtalen-2-yloxy?acetate
hydrochloride) on hypoxia-induced pulmonary vasoconstriction, and (b) to
investigate the potential existence of atypical beta-adrenoceptors in these
effects. Propranolol (0.1 microM) was used to antagonize beta1- and beta2
adrenoceptors whereas SR 59230A, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4
tetrahydronapht-1-ylam ino]-(2S)-2-propanol oxalate) (0.3 microM) was used to
block beta3-adrenoceptors. Isoprenaline and the three beta3-adrenoceptors
agonists caused concentration-dependent relaxations during the pulmonary pressure
response. Propranolol and SR 59230A inhibited the relaxant effects of
isoprenaline. SR 59230A but not propranolol inhibited those of SR 59104A.
Finally, propranolol and SR 59230A failed to oppose SR 59119A- and SR 58611A
induced relaxant effects. In concentrations > or = 1 microM, SR 59230A caused per
se a relaxation of the hypoxic vasoconstricted lung. These results suggest the
existence of atypical beta-adrenoceptors in the rat pulmonary vessels.
PMID- 9652338
TI - Cardioprotective effects of quinapril after myocardial infarction in hypertensive
rats.
AB - Although angiotensin-converting enzyme inhibitors are beneficial for patients
with congestive heart failure, the appropriate timing and dosage in acute
myocardial infarction are still controversial. We examined the hemodynamic
effects of quinapril administered before acute myocardial infarction in
spontaneously hypertensive rats (SHR). Quinapril (10 mg/kg per day in drinking
water) was started 1 week before infarction and continued for 4 weeks after
infarction (total duration 5 weeks). The hemodynamic parameters were evaluated by
cardiac catheterization 4 weeks after coronary ligation. Sham-operated SHR served
as controls. After infarction, left ventricular end-diastolic and right atrial
pressures were increased (P < 0.01) and blood pressure and cardiac index were
decreased (P < 0.01); the magnitude of blood pressure reduction was similar in
the treated and untreated rats with infarction. Quinapril improved these
hemodynamic parameters significantly and decreased left and right ventricular
weight. These results suggest that a prior treatment with quinapril in SHR with
acute myocardial infarction is hemodynamically beneficial.
PMID- 9652339
TI - Respiratory effects of glutamate receptor antagonists in neonate and adult
mammals.
AB - We determined the conditions (immaturity, species, anesthesia, receptor blockade
selectivity) under which glutamate receptor blockade produces respiratory
depression in mammals. In unrestrained 0- to 2-day-old neonate and adult mice and
cats, ventilation was measured by the barometric method, before and after
separate or sequential administration of a non-NMDA receptor antagonist, NBQX
(2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline, 2-200 mg kg(-1) in mice,
10-40 mg kg(-1) in cats), and a NMDA receptor antagonist, dizocilpine (3 mg kg(
1) in mice, 0.15-1.0 mg kg(-1) in cats). NBQX or dizocilpine alone did not
decrease ventilation in awake adults, but NBQX strongly depressed ventilation in
neonate awake mice and in adult anesthetized animals. Given together, dizocilpine
and NBQX always profoundly depressed ventilation by producing a lethal apnea in
neonate mice, and an apneustic pattern of breathing in adults of both species and
in neonate cats. We conclude that blockade of either NMDA or non-NMDA receptors
is innocuous in awake adults. The factors which may potentiate respiratory
depression are (1) anesthesia, (2) immaturity, and (3) combined blockade of both
receptors types. The mechanism of depression is species-dependent and age
dependent.
PMID- 9652340
TI - Nitric oxide enhances prostaglandin production in ethanol-induced gastric mucosal
injury in rats.
AB - The interaction between endogenous nitric oxide (NO), elicited by administration
of Escherichia coli lipopolysaccharide, and cyclooxygenase system, in ethanol
induced injury in rat gastric mucosa, was investigated. Administration of graded
doses of lipopolysaccharide reduced the gastric mucosal injury in response to
ethanol. The ex vivo production of both nitrite and prostaglandin E2 was
increased in dose-related manner by lipopolysaccharide. Pretreatment with
dexamethasone, L-N6-(1-Iminoethyl)lysine(dihydrochloride) and L-NG-nitro arginine
methyl ester inhibited the protection associated with lipopolysaccharide
treatment and the ex vivo production of both, nitrite and prostaglandin E2. The
pretreatment with L-arginine counteracted the decrease of nitrite and
prostaglandin E2 production in lipopolysaccharide-treated rats in which nitric
oxide synthesis was blocked by L-N6-(1-Iminoethyl)lysine(dihydrochloride).
Administration of sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine
caused a dose related enhancement in the accumulation of prostaglandin E2.
Indomethacin administration and N-(2-Cyclohexyloxy-4
nitrophenyl)methanesulfonamide were ineffective in suppressing lipopolysaccharide
mediated protection against ethanol-induced damage, and in suppressing ex vivo
increase of nitrite whereas the ex vivo increase of prostaglandin E2 was
prevented in a dose-related fashion. These results indicate that in ethanol
induced rat gastric injury, endogenous NO elicited by lipopolysaccharide or
released by NO donors is able to activate the cyclooxygenase pathway, and the
protective effect of lipopolysaccharide is dependent upon NO formation.
PMID- 9652341
TI - Prostaglandin, tumor necrosis factor alpha and neutrophils: causative
relationship in indomethacin-induced stomach injuries.
AB - Tumor necrosis factor alpha (TNF-alpha) has been suggested to play a critical
role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal
level and its relationship with prostaglandin E2 and neutrophils in indomethacin
induced gastric mucosal injury in rats. Indomethacin caused a time- and dose
dependent increase in gastric mucosal erosion, which was accompanied by a
reduction in prostaglandin E2 followed by an increase in TNF-alpha level and
neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous
prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury
and the TNF-alpha increase. Depletion of neutrophils by methotrexate or reduction
of TNF-alpha concentration by pentoxifylline markedly reduced indomethacin
induced mucosal damage. Pentoxifylline but not methotrexate prevented the
increase in mucosal TNF-alpha level induced by indomethacin. It is suggested that
depletion of prostaglandin E2 followed by an increase of TNF-alpha production and
neutrophil infiltration in the gastric mucosa are important sequential processes
in indomethacin-induced ulceration. Prevention of one of these processes would
inhibit ulcer formation.
PMID- 9652342
TI - Pancreatic islet responsiveness to D-glucose after repeated administration of
repaglinide.
AB - The influence of three daily oral doses of repaglinide (1.0 microg/g body wt.) on
plasma insulin and glucose concentrations, pancreatic islet insulin content and
both protein biosynthesis and insulin release in isolated islets incubated for 90
min in the presence of either 2.8 or 16.7 mM D-glucose was examined in both
control and hereditary diabetic Goto-Kakizaki (GK) rats. In the control rats,
repaglinide lowered the plasma glucose concentration, whilst failing to affect
significantly the plasma insulin concentration or insulin/glucose ratio, 24 h
after the last administration of the antidiabetic agent. Despite a severe
decrease of islet insulin content, the ratio between insulin release and content
was not altered in islets obtained from repaglinide-treated control rats and
incubated in the presence of 16.7 mM D-glucose. Also the biosynthesis of islet
peptides was increased at both low and high hexose concentrations. In GK rats,
repaglinide administration affected neither plasma glucose nor insulin
concentration, restored a normal value for the otherwise abnormally high basal
insulin output, increased the 16.7 mM/2.8 mM ratio for insulin release, and again
augmented protein biosynthesis at both low and high hexose concentrations. In
both control and GK rats, the stress induced by bleeding and decapitation
augmented plasma glucose concentration. This effect was more pronounced in GK
than in control rats and, in the diabetic animals, coincided with a severe
lowering of the plasma insulin/glucose ratio, suggesting a higher adrenergic
sensitivity of islet cells in the GK than in control rats. The increased
secretory responsiveness to glucose and increased biosynthetic activity found in
islets from GK rats after repaglinide administration, are considered favourable
attributes of this meglitinide analogue in the perspective of its use as an
insulinotropic agent in noninsulin-dependent diabetes.
PMID- 9652343
TI - A possible mechanism underlying corymine inhibition of glycine-induced Cl-
current in Xenopus oocytes.
AB - We previously reported that corymine, an alkaloid extracted from the leaves of
Hunteria zeylanica native to Thailand, inhibited glycine-induced chloride current
using a receptor expression model of Xenopus oocytes. In this study, we
investigated the mechanism underlying the inhibitory action of this alkaloid on
glycine current using the same model. Corymine inhibited glycine current in a
noncompetitive fashion. Co-application with strychnine, a competitive glycine
receptor antagonist, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS),
a Cl- channel blocker, corymine decreased the ED50 value of strychnine, but did
not change that of DIDS. Moreover, the inhibitory effects of corymine and either
strychnine or DIDS were additive. The desensitization phase of glycine current
showed two exponentials and corymine preferentially inhibited the fast component,
whereas strychnine affected both of them to the same extent and DIDS
preferentially inhibited the slow component. When these drugs were applied
repeatedly, the inhibitory effects of corymine and strychnine were not use
dependent and reversible, while the effect of DIDS was use-dependent and
irreversible. The inhibitory effect of corymine on gamma-aminobutyric acid (GABA)
current was less potent than the effect on glycine current, while this alkaloid
failed to affect acetylcholine and serotonin currents. These results demonstrate
that corymine inhibits glycine-gated CI- channels by interacting with the site
different from that of DIDS.
PMID- 9652344
TI - Human 5-HT1B receptor stimulated inositol phospholipid hydrolysis in CHO cells:
synergy with Gq-coupled receptors.
AB - We have previously reported that the transfected Gi/Go protein-coupled human
adenosine A1 receptor (expressed at 200 fmol/mg of protein) and the endogenous 5
HT1B receptor (not detectable using radioligand binding) suppress forskolin
stimulated cyclic AMP accumulation and stimulate increases in [Ca2+]i in Chinese
hamster ovary cells (CHO). In addition, co-activation of the adenosine A1
receptor (but not the 5-HT1B receptor) potentiates the hydrolysis of inositol
phospholipids elicited by receptors coupled to Gq-proteins (Dickenson and Hill,
1996. Eur. J. Pharmacol. 320, 141-151). In order to establish whether this
difference in ability to modulate Gq-coupled receptor responses is a consequence
of low 5-HT1B receptor density, we have stably transfected CHO-KI cells with the
human 5-HT1Dbeta cDNA (the human homologue of the rodent 5-HT1B receptor). We
initially isolated a clonal cell line (designated CHO5-HT1B cells) displaying
moderate specific [3H]5-HT binding (pKd of 8.17+/-0.07 and a Bmax of 140 fmol/mg
protein). In CHO5-HT1B cells, the selective human 5-HT1B/1D receptor agonist
sumatriptan produced a concentration-dependent inhibition of forskolin-stimulated
cyclic AMP accumulation (pEC50=7.92+/-0.04). Sumatriptan also elicited a moderate
and pertussis toxin-sensitive increase in [3H]inositol phosphate formation in CHO
5HT1B cells (pEC50=6.51+/-0.05). Finally, sumatriptan synergistically enhanced
P2U purinoceptor stimulated [3H]inositol phosphate accumulation through a
pertussis toxin-sensitive mechanism. These findings clearly show the significance
of 5-HT1B receptor expression level in determining whether 5-HT1B receptor
activation can modulate the accumulation of [3H]inositol phosphates elicited by a
Gq-protein coupled receptor. The observation that 5-HT1B receptor activation can
potentiate Gq-coupled receptor stimulated second messenger responses may have an
important physiological role in the regulation of vascular smooth muscle
contraction.
PMID- 9652345
TI - Characterization of specific binding of [125I]L-762,459, a selective alpha1A
adrenoceptor radioligand to rat and human tissues.
AB - L-762,459 ((+/-)1-(3-?[5-carbamoyl-2-2-[(4-hydroxy-3-iodobenzimidoyl)-amino]
ethoxy-methy?-6-methyl-4-(4-nitropheny)-1,4-dihydropyridine -3-carbonyl]-amino?
propyl)-4-phenyl-1-piperidine-4-carboxylic acid methyl ester), an analog of a
series of dihydropyridines previously reported to be selective alpha1A
adrenoceptor subtype antagonists was found to have alpha1A-adrenoceptor subtype
selectivity (Ki (nM), la = 1.3, lb = 240, Id = 280). Specific [125I]L-762,459
binding was detected in rat cerebral cortex, hippocampus, vas deferens, kidney,
heart and prostate tissues known to contain the alpha1A-adrenoceptor subtype, but
not in tissues known to contain alpha1B-adrenoceptor (spleen, liver) and alpha1D
adrenoceptor (aorta). Scatchard analysis of [125I]L-762,459 binding in rat
cerebral cortex and prostate indicated a single binding site with a Kd of 0.7 nM
and Bmax of 11 (cerebral cortex) and 1 (prostate) pmole/g tissue. Specific and
saturable [125I]L-762,459 binding was also found in human cerebral cortex, liver,
prostate and vas deferens (Kd = 0.2-0.4 nM, Bmax = 0.4-4 pmole/g tissue). The
specific binding in rat and human tissues was competed by non-selective alpha1
adrenoceptor compounds (Ki values in nM: prazosin (0.14-1.2), terazosin (1.8-5.9)
and phentolamine (2.4-11)) and selective alpha1A-adrenoceptor compounds [Ki
values in nM: (+) niguldipine (0.04-1.2) and SNAP 5399 ((+/-)-2-((2
aminoethyl)oxy)methyl-5-carboxamido-6-ethyl-4-(4-nitropheny l)-3-N-(3-(4,4
diphenylpiperidin-1-yl)propyl)carboxamido-1,4-dihyd ropyridine hydrate (0.5
4.8)]. The results were consistent with the selective binding of [125I]L-762,459
to the alpha1A-adrenoceptor. The specific labeling of the alpha1A-adrenoceptor
subtype by [125I]L-762,459 may make it a useful tool to localize the distribution
of the alpha1A-adrenoceptor.
PMID- 9652346
TI - Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.
AB - Using the human lung epithelial WI26VA4 cell line, we investigated the capacity
of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties,
to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid
formation. Histamine and a histamine H1 receptor agonist elicited a rapid and
transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells.
This response was antagonized by the histamine H1 receptor antagonist,
diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no
effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced
Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic
acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid
release, was responsible for the histamine-induced intracellular Ca2+ increase.
In the second phase release (15-60 min), a sustained arachidonic acid release
appeared to be associated with the formation of cyclooxygenase and lipoxygenase
metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced
arachidonic acid release. These results suggest that anti-inflammatory and
antibronchoconstrictor properties of fenspiride may result from the inhibition of
these effects of histamine.
PMID- 9652347
TI - Endothelin-1-(1-31), a novel vasoactive peptide, increases [Ca2+]i in human
coronary artery smooth muscle cells.
AB - We have previously found that human chymase cleaves big endothelins at the Tyr31
Gly32 bond and produces 31-amino acid long endothelins-(1-31), without any
further degradation products. In this study, we investigated the effect of
synthetic endothelin-1-(1-31) on the intracellular free Ca2+ concentration
([Ca2+]i) in cultured human coronary artery smooth muscle cells. Endothelin-1-(1
31) increased [Ca2+]i in a concentration-dependent manner (10(-14) to 10(-10) M).
This endothelin-1-(1-31)-induced [Ca2+]i increase was not affected by
phosphoramidon (N-(alpha-Rhamnopyranosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptoph
an), an inhibitor of endothelin-converting enzyme. It was, however, inhibited by
10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)), an endothelin ET(A)
receptor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6
dimethylpiperidinocarbonyl-L-yMeLeu-D-Trp(COOM e)-D-Nle-ONa), an endothelin ET(B)
receptor antagonist. These results suggest that endothelin-1-(1-31) by itself
exhibits vasoactive properties probably through endothelin ET(A) receptors. Since
human chymase has been reported to play a role in atherosclerosis, endothelin-1
(1-31) may be one of the candidate substances for its cause.
PMID- 9652348
TI - [125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors.
AB - Human somatostatin (somatotropin release inhibiting factor = SRIF) receptor
subtypes sst2 and sst5 were stably expressed in Chinese hamster lung fibroblast
(CCL39) cells. [125I][Tyr3]octreotide labelled with high affinity and in a
saturable manner both sst2 (pKd = 9.89+/-0.02, Bmax = 210+/-10 fmol/mg, n = 3)
and sst5 sites (pKd = 9.64+/-0.04, Bmax = 920+/-170 fmol/mg, n = 3). The
pharmacological profile of sst2 sites established in CCL39 cells using SRIF and
various peptide analogues was very similar to that described previously in CHO
cells and in human cortex: SRIF14 = SRIF28 > or = seglitide > BIM 23014 = RC 160
> octreotide > CGP 23996 > or = L362,855 > BIM 23052 > L361,301 = cortistatin14 >
BIM 23030 > BIM 23056 > cycloantagonist SA. However, peptides classically
perceived as sst2 receptor selective (e.g., seglitide, octreotide, vapreotide)
showed also high affinity for human sst5 receptors labelled with
[125I][Tyr3]octreotide: SRIF28 > seglitide > SRIF14 > L361,301 = octreotide >
cortistatin14 = BIM 23014 = BIM 23052 > L362,855 = RC160 > CGP 23996 > BIM 23056
> cycloantagonist SA > BIM 23030. Further radioligand binding studies were
performed with [Leu8,D-Trp22,125I-Tyr25]SRIF28 ([125I]LTT-SRIF28) and [125I]CGP
23996. At sst2 receptors, Bmax values determined with [125I][Tyr3]octreotide,
[125I]LTT-SRIF28 and [125I]CGP 23996 were in the same range (180-370 fmol/mg). 5'
Guanylyl-imidodiphosphate (GppNHp) displaced all three radioligands to the same
extent (85%) and the pharmacological profiles were superimposable. By contrast,
at sst5 receptors Bmax values were very different: [125I][Tyr3]octreotide (920
fmol/mg), [125I]CGP 23996 (3530 fmol/mg) and [125I]LTT-SRIF28 (6950 fmol/mg).
GppNHp affected [125I][Tyr3]octreotide more than [125I]CGP 23996 binding, whereas
[125I]LTT-SRIF28 was much less affected. In addition, the affinity values
determined in competition experiments at sst5 receptors, varied markedly; whereas
SRIF14, cortistatin14 and SRIF28 showed 2-, 4- and 8-fold differences in affinity
at sst5 receptors labelled with [125I][Tyr3]octreotide and [125I]LTT-SRIF28
compounds such as RC160, L363,301, L362,855, octreotide or CGP 23996 showed
between 42- and 123-fold lower affinity when sst5 sites were labelled with
[125I]LTT-SRIF28. The present data suggest caution to be used when comparing
affinity profiles determined in binding studies using different radioligands. In
addition, the present results suggest that effects produced by octreotide and
related short chain SRIF analogues on hormone release, modulation of tumour
growth and central effects may be mediated by either sst2 and/or sst5 receptors.
PMID- 9652349
TI - Regulation of GABA(A) receptor alpha1 protein is a sensitive indicator of
benzodiazepine agonist efficacy.
AB - The effect of benzodiazepine agonists of varying efficacy on gamma-aminobutyric
acidA receptor alpha1 subunit protein expression was determined in primary
cultured cerebellar granule cells. After 48 h exposure to 1 microM drug
concentrations, flunitrazepam, diazepam, and the partial agonists Ro 19-8022 and
bretazenil, but not the partial agonists Ro 42-8773, Ro 41-7812 or imidazenil,
decreased alpha1 subunit protein expression. The grading of effect of the
benzodiazepine partial agonists on alpha1 subunit protein expression is
consistent with their agonist efficacies. This model, therefore, appears to act
as a sensitive indicator of benzodiazepine agonist efficacy with the ability to
differentiate between partial agonists.
PMID- 9652350
TI - Identification of adenylyl cyclase isoenzymes in CHO and B82 cells.
AB - The identification of adenylyl cyclase isoenzymes in mammalian host cells is
important for the interpretation of data obtained from cell lines heterologously
expressing G-protein coupled receptors. Reverse transcriptase polymerase chain
reaction (RT-PCR) was used to amplify adenylyl cyclase cDNAs from Chinese hamster
ovary (CHO) and mouse fibroblast (B82) cells. The isolated fragments were
identified by restriction analyses and by sequencing. We found mRNAs for adenylyl
cyclases VI and VII in CHO and adenylyl cyclases IX and VII in B82 cells.
PMID- 9652351
TI - Nicorandil affects diurnal rhythms of body temperature, heart rate and locomotor
activity in rats.
AB - The effects of nicorandil, a K+ channel opener with a potent vasodilator action,
on diurnal rhythms of body temperature, heart rate and locomotor activity were
assessed in rats. Transmitters were intraperitoneally implanted under ether
anaesthesia. After recovery from surgery, body temperature, heart rate and
locomotor activity were recorded during control, saline or nicorandil (10 mg x
kg(-1) administered orally) treatment and for 5 days after treatment. For each
period, Fourier analysis determined the predominant rhythmicity for body
temperature, heart rate and locomotor activity while cosinor analysis assessed
the corresponding mesors, acrophases and amplitudes and maxima and minima were
directly plotted from raw data. The results indicated: (1) loss of the diurnal
rhythmicity for all three rhythms after implantation; (2) stress-induced
modifications of almost all the characteristics of the three rhythms after saline
and (3) a loss of diurnal rhythmicity of heart rate after nicorandil, an effect
that was not observed after saline and which was reversed when nicorandil
administration was stopped. In conclusion, nicorandil perturbed the diurnal
rhythmicity of heart rate while the rhythmicity of body temperature and locomotor
activity was not affected.
PMID- 9652352
TI - Pharmacokinetic-pharmacodynamic modeling of the coexistence of stimulatory and
sedative components for midazolam.
AB - Midazolam increased the shorter-response rate and decreased the reinforcement
rate of a contingency-controlled timing behavior--a differential-reinforcement-of
low-rate 45-s schedule. The responding rate changes observed were immediately
interpretable as functions of midazolam concentration during a 3-h session--a
period for investigating the onset, peak, and disappearance of midazolam effect-
in rats. That the midazolam pharmacokinetic-pharmacodynamic model was a direct
application of our alprazolam pharmacokinetic-pharmacodynamic model implies that
both drugs exhibit similar pharmacological effects. The two peaks of the shorter
response rate increases produced by midazolam were modeled as a stimulation
sedation model that consisted of two opposing effect-link sigmoidal Emax
functions. The stimulation-sedation model suggested that midazolam possesses both
stimulatory and sedative effects in a continuous but sequential fashion, and
hypothesizes the coexistence of stimulation and sedation components for
midazolam; this model may help delineate possible mechanisms for rebound side
effects and of tolerance in humans. The reinforcement rate was, then, an index
for evaluating the deficit in timing performance.
PMID- 9652353
TI - Na+ channel block prevents the ischemia-induced release of norepinephrine from
spinal cord slices.
AB - The principal finding of the present study with rat spinal cord slices was the
novel demonstration of the [Ca2+]o-independent effect of ischemia on
norepinephrine release and its antagonism by tetrodotoxin and low temperature (10
degrees C). Our finding that tetrodotoxin antagonized the effects of glucose
deprivation on norepinephrine release in a [Ca2+]o-independent way suggests that
Na+ channel block alone, i.e., the prevention of Na+ accumulation, may account
for the protective action. Low temperature completely prevented the effect of
ischemia on norepinephrine release but did not change the release associated with
axonal activity. This finding is in good agreement with the observation that
small changes in brain temperature critically determine the extent of neuronal
injury from ischemia and suggests that both [Ca2+]o-independent release and cell
injury are associated with the norepinephrine membrane carrier. It is suggested,
therefore, that drugs able to attenuate the increase in [Na+]i during ischemia
may be useful agents to protect against ischemic damage if given before the
insult.
PMID- 9652354
TI - Temporal dependent neuroprotection with propentofylline (HWA 285) in a temporary
focal ischemia model.
AB - Propentofylline (HWA 285, 3-methyl-1-(5-oxo-hexyl)-7-propylxanthine) is an
adenosine uptake and phosphodiesterase inhibitor that has been shown to be
neuroprotective in both global and permanent focal ischemia animal models.
However, to date, the efficacy of propentofylline has never been examined in an
animal model of temporary focal ischemia or the 'therapeutic window'
systematically examined in a focal ischemia model. The present experiments were
designed to investigate these. Temporary (3 h) middle cerebral artery occlusion
was accomplished by the monofilament method. Infarct volumes were determined at
24 h from 2,3,5-triphenyltetrazolieum chloride (TTC) stained coronal slices.
Animals were dosed with vehicle or propentofylline at 3 mg/kg bolus and/or a 6
mg/kg per h infusion (24 h infusion) at 30 min, 1 h or 3 h post ischemia onset.
Physiological monitoring on a subset of animals indicated no changes in mean
arterial pressure, blood gases, blood pH, and glucose levels with either ischemia
or drug treatment. Propentofylline treatment resulted in a statistically
significant decrease in infarct volume when an infusion dose of 6 mg/kg per h was
initiated at 30 min or when a bolus of 3 mg/kg plus an infusion dose was
initiated at 1 h but not 3 h post ischemia. Therefore, propentofylline is
neuroprotective in a model of temporary focal ischemia. This suggests that
combination therapy with propentofylline might lead to clinical improvement
beyond that which would occur with thrombolytics alone. The apparent short window
of opportunity for effective dosing is consistent with the proposed mechanism of
action for propentofylline.
PMID- 9652355
TI - The effect of the adrenocorticotropin-(4-9) analogue, ORG 2766, and of
dizolcipine (MK-801) on infarct volume in rat brain.
AB - The purpose of this study was to evaluate whether the synthetic
adrenocorticotropin-(4-9) (ACTH-(4-9)) analogue ORG 2766, HMet(O2)-Glu-His-Phe-D
Lys-Phe-OH, which has been shown to have beneficial effects on both the recovery
from experimentally induced lesions of the central nervous system and peripheral
nerve degeneration, has a protective effect on focal ischemic neuronal damage.
The NMDA receptor antagonist dizolcipine (MK-801), a very potent neuroprotective
drug, was used as positive reference compound. Isoflurane-anesthetized rats had
the middle cerebral artery occluded using either an intravasal or an extravasal
technique, because pilot experiments had shown differences in the severity of
ischemia for the two middle cerebral artery occlusion techniques. MK-801, 500
microg kg(-1) min(-1), or saline was administered i.v. 30 min after occlusion of
the middle cerebral artery. In the ACTH-(4-9) analogue/saline group, 10 and 150
microg/kg of the analogue, or saline was injected s.c. both directly after and 24
h after occlusion. The ACTH-(4-9) analogue treatment had no effect on the
infarction volume in either model of middle cerebral artery occlusion, whereas MK
801 caused a significant reduction in the volume of cortical infarction in both
models. We conclude that, although ORG 2766 is known to enhance the recovery from
experimentally induced lesions of the central nervous system through a
neurotrophic action and has proven to have significant beneficial effects on
peripheral nerve regeneration, it did not prevent ischemic neuronal damage after
intravasal or extravasal middle cerebral artery occlusion in rats. The results
with MK-801, which caused significant reductions in the volume of cortical
infarction in both models of middle cerebral artery occlusion, with clearly the
largest reduction in the intravasal middle cerebral artery occlusion model, again
indicate that there are differences in the severity of the cerebral ischemia
which the two models produce in the rat brain.
PMID- 9652356
TI - Modulatory effect of bradykinin on noradrenaline release in isolated atria from
normal and B2 knockout transgenic mice.
AB - The modulatory effect of bradykinin on electrically-induced noradrenaline release
was assessed in isolated atria from normal and B2 knockout transgenic mice
preincubated with [3H]noradrenaline. Concentrations of 1, 3 and 10 nM of
bradykinin did not significantly alter the outflow of radioactivity whereas
higher concentrations of bradykinin (30 and 100 nM) enhanced it. The facilitatory
effect of 30 nM bradykinin was inhibited by a selective bradykinin B2 receptor
antagonist. Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, 30 nM), and by a
protein kinase C inhibitor, bisindolylmaleimide (1 microM). The co-administration
of bradykinin (1 to 100 nM) with either [Leu8]des-Arg9-bradykinin (100 nM),
AcLys[DbetaNal7,Ile8]des-Arg9-bradykinin (30 nM) (bradykinin B1 receptor
antagonists) or diclofenac (1 microM) (a cyclooxygenase inhibitor), shifted the
facilitatory effect of bradykinin to lower concentrations. The facilitatory
effect of bradykinin also was enhanced by enalaprilat (1 microM) and mergetpa (1
microM), inhibitors of angiotensin-converting enzyme (kininase II) and kininase
I, respectively. In contrast, selective bradykinin B1 receptor agonists, des-Arg9
bradykinin (1 to 100 nM) and Sar[D-Phe8]des-Arg7-bradykinin (1 to 100 nM), did
not significantly affect the stimulation-induced outflow of radioactivity.
Neither bradykinin (100 nM) nor des-Arg9-bradykinin (100 nM) had any modulatory
effect in B2 knockout transgenic mice. These findings suggest that the
facilitatory effect of bradykinin on noradrenaline release in the mouse atria is
mediated exclusively by presynaptic bradykinin B2 receptors which are linked to
protein kinase C. The greater release of noradrenaline with bradykinin under
inhibition of prostaglandins production and kininases I and II activity might be
of importance in pharmacotherapies.
PMID- 9652357
TI - Differential effects of 5-HT1B/1D receptor antagonists in dorsal and median raphe
innervated brain regions.
AB - The effect of SB-224289 (2,3,6.7-tetrahydro-1'-methyl-5-?2'-methyl-4'-[(5-methyl
1,2,4-oxadiazol e-3-yl)biphenyl-4-yl]carbonyl?Furo[2,3-F]-indole-3-spiro-4'
piperidine oxalate) (4 mg/kg i.p., 5-HT1B receptor antagonist), GR 127935 (N-[4
methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4
oxadiazole-3-yl)[1,1'-biphenyl]-carboxamide) (0.3 mg/kg i.p., 5-HT1B/1D receptor
antagonist), and paroxetine (10 mg/kg p.o.) were investigated on extracellular 5
hydroxytryptamine (5-HT) levels in the frontal cortex, striatum and dentate gyrus
of the freely moving guinea-pig with microdialysis. In the frontal cortex and
striatum (dorsal raphe innervated areas), GR 127935 evoked a significant decrease
in extracellular 5-HT, reaching minima of 41+/-12% and 32+/-6% of basal,
respectively. This decrease may be explained by antagonism of inhibitory 5
HT1B/1D receptors on raphe cell bodies, leading to a local increase in 5-HT,
which, in turn, stimulated 5-HT1A receptors to decrease cell firing, and hence 5
HT release from terminals. In contrast, SB-224289 had no effect on 5-HT levels in
either region. In the dentate gyrus (median raphe innervated area), GR 127935 and
SB-224289 significantly increased extracellular 5-HT, reaching maxima of 146+/
11% and 151+/-19% of basal, respectively. The ability of both compounds to
increase 5-HT levels in the dentate gyrus suggests a lack of 5-HT1B/1D receptors
in the median raphe nucleus. Paroxetine produced a small but non-significant
increase in extracellular 5-HT in the frontal cortex, and a small decrease in the
dentate gyrus. The lack of effect of paroxetine in terminal areas may be due to
the limiting effects of cell body 5-HT autoreceptors. In summary, the above data
demonstrate that 5-HT1B/1D receptor antagonists increase 5-HT levels in the
dentate gyrus, implying that acute administration of 5-HT1B/1D receptor
antagonists will achieve a similar effect to chronic selective serotonin re
uptake inhibitor treatment in median raphe innervated areas. This, in turn,
suggests that such compounds may be efficacious in the treatment of depression.
PMID- 9652358
TI - MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced
hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion.
AB - One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA
HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by
approximately 25-30% in the frontal cortex and hypothalamus of rats. The
increased density correlated with the potentiation of the hypothermic response to
the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1
mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not
changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.)
or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the
depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the
effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced
hypothermia. The protection afforded by drugs against 5-HT loss did not
correlate, however, with the antagonism of the acute hyperthermic effect of MDMA.
The present results indicate that drugs able to prevent or to attenuate MDMA
induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as
the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in
MDMA-treated rats.
PMID- 9652359
TI - Modulation of amphetamine-stimulated (transporter mediated) dopamine release in
vitro by sigma2 receptor agonists and antagonists.
AB - Some sigma receptor ligands have been shown to bind with low affinity to the
dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously
been shown whether any of these compounds influence release of dopamine via
facilitated exchange diffusion. To further examine the nature of the interaction
between sigma receptor ligands and the dopamine transporter, the effects of sigma
receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in
slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both
(+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated
[3H]dopamine release at concentrations consistent with their affinities for
sigma2 receptors. In contrast, BD737 (1S.2R-(-)-cis-N-?2-(3,4
dichlorophenyl)ethyl?-N-methyl-2-(1-pyrrolidiny l)cyclohexylamine), a sigma1
receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer
of pentazocine alone had any effect on basal [3H]dopamine release under these
conditions. Three antagonists at sigma receptors, one of which is non-selective
for subtypes, and two of which are sigma2-selective, all blocked the enhancement
of stimulated release produced by (+)-pentazocine. Enhancement of stimulated
release by (-)-pentazocine was similarly blocked by sigma2 receptor antagonists.
Our data support the contention that it is possible to regulate transporter
mediated events with drugs that act at a subpopulation of sigma receptors
pharmacologically identified as the sigma2 subtype.
PMID- 9652360
TI - Tonic GABA(A) receptor-mediated neurotransmission in the dorsal vagal complex
regulates intestinal motility in rats.
AB - Vagal motor outflow from the dorsal vagal complex is important in the regulation
of intestinal motility. The aim of our study was to test the hypothesis that
within the dorsal vagal complex, tonic GABA(A)-receptor mediated
neurotransmission modulates intestinal motility. The GABA(A) receptor antagonist,
bicuculline (methiodide), was microinjected into the dorsal vagal complex, and
the effects on small intestinal and colonic motility were investigated. Rats were
anesthetized and the mean arterial pressure and heart rate were monitored.
Jejunal and colonic motility were measured manometrically, and motility indices
were calculated manually. Bicuculline at concentrations of 0.25 or 0.5 mM in 30
nl was microinjected bilaterally into the dorsal vagal complex through
stereotaxically placed micropipettes. The injection sites were confirmed
histologically using the dye Alcian Blue. Bicuculline (0.5 mM) inhibited
spontaneous jejunal motility by 76.3%, colonic motility by 51.7%, mean arterial
pressure by 23.3% and heart rate by 27.6%. The lower concentration of bicuculline
(0.25 mM) showed no inhibitory effects on intestinal motility but decreased mean
arterial blood pressure by 24.1% and heart rate by 13.6%. Bilateral cervical
vagotomy attenuated the bicuculline (0.5 mM)-induced inhibition of spontaneous
jejunal motility, whereas the bicuculline effect on colonic motility was
unaffected. The results of this study show that GABA(A) receptor-mediated
neurotransmission in the dorsal vagal complex is involved in autonomic
integration of motility of the small intestine and colon. Furthermore, our
results indicate that the dorsal vagal complex regulation of jejunal motility
involves vagal outflow, whereas vagal pathways do not participate in the
bicuculline-induced inhibition of colonic motility.
PMID- 9652361
TI - Dissociation of morphine-induced potentiation of turning and striatal dopamine
release by amphetamine in the nigrally-lesioned rat.
AB - Morphine has been reported to increase extracellular levels of dopamine in the
brain of intact rats and to potentiate turning induced by amphetamine in nigrally
lesioned rats. The present study tested the hypothesis that there is a causal
relationship between these two effects of morphine. We tested morphine alone,
amphetamine alone, and the combination in separate groups of nigrally-lesioned
rats for effects on turning and, by microdialysis, on extracellular dopamine
levels. Morphine (3.0 or 10 mg/kg) did not produce significant turning but
amphetamine (1.0 mg/kg) did. The lower dose, but not the higher dose, of morphine
potentiated amphetamine-induced turning. Amphetamine, but not morphine, produced
increases in extracellular dopamine levels. In contrast to what occurred with
turning, 10 mg/kg but not 3.0 mg/kg morphine potentiated amphetamine-induced
increases in extracellular dopamine levels. These results show that the
potentiation of amphetamine-induced turning by morphine in nigrally-lesioned rats
is not due to the potentiation of dopamine release in the intact striatum.
PMID- 9652362
TI - Differential regional antagonism of 8-OH-DPAT-induced decrease in serotonin
synthesis by two 5-HT1A receptor antagonists.
AB - The effects of two 5-HT1A receptor antagonists, (R)-3-N, N-dicyclobutylamino-8
fluoro-3,4-dihydro-2 H-1-benzopyran-5-carboxamide hydrogen (2 R,3 R)-tartrate
monohydrate (NAD-299) and N-(2-(1-(2-methoxyphenyl)-piperazinyl))ethyl)-N-(2
pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) on the decrease
in 5-hydroxytryptophan (5-HTP) accumulation evoked by (RS)-2-dipropylamino-8
hydroxy-1,2,3,4-tetrahydronaphthalene (8-OH-DPAT) in rats treated with the
decarboxylase inhibitor, 3-hydroxyphenylhydrazine (NSD 1015) were studied in four
rat brain regions: hippocampus, hypothalamus, striatum and frontal cortex. Dose
response studies revealed differential effects of both antagonists in the areas
examined. Both antagonists were significantly more potent in antagonising the
effect of 0.30 and 0.76 micromol/kg s.c. 8-OH-DPAT in hippocampus than in
hypothalamus, striatum and frontal cortex in mentioned order. This order of
potency was the opposite to that found for 8-OH-DPAT in decreasing the 5-HTP
accumulation. Since previous studies by others have indicated that the reserve of
somatodendritic 5-HT1A receptors is greater in dorsal raphe nucleus innervating
frontal cortex and striatum than in median raphe nucleus which mainly innervates
hippocampus, the observed different regional potency of the two 5-HT1A receptor
antagonists may be explained by this difference in the 5-HT1A receptor reserve.
PMID- 9652363
TI - The role of P-selectin, sialyl Lewis X and sulfatide in myocardial ischemia and
reperfusion injury.
AB - The role of P-selectin and the ligands of selectins such as sialyl Lewis X and
sulfatide was studied in a myocardial ischemia and reperfusion injury model.
Anesthetized rabbits underwent the occlusion of coronary artery (30 min) followed
by reperfusion (5 h). The inhibitory effect on myocardial ischemia and
reperfusion injury was examined with infarct size normalized by area-at-risk.
Intravenous administration of an anti-P-selectin monoclonal antibody, PB1.3 (2
mg/kg), reduced infarct size by 38%. Similarly, the administration of sialyl
Lewis X-oligosaccharide (10 mg/kg) reduced infarct size by 53% significantly.
Finally, the infarct size was significantly reduced bv 39% in sulfatide-treated
group (10 mg/kg). These results suggest that P-selectin plays an important role
in myocardial ischemia and reperfusion injury and that the ligands of selectins,
such as sialyl Lewis X-oligosaccharide and sulfatide, have cardioprotective
effect on myocardial ischemia and reperfusion injury.
PMID- 9652364
TI - Muscarinic M1 receptor activation reduces maximum upstroke velocity of action
potential in mouse right atria.
AB - We investigated whether acetylcholine affects cardiac action potentials through
the muscarinic M1 in addition to M2 receptors in spontaneously beating mouse
isolated right atria. A conventional glass microelectrode technique was used for
the purpose. Acetylcholine (3-10 microM) reduced the maximum upstroke velocity of
the action potentials (Vmax), followed by an increase. It shortened action
potential duration at 90% repolarization, hyperpolarized the resting membrane and
decreased the rate of beating. Atropine (3-100 nM) concentration dependently
antagonized these effects of acetylcholine. Pirenzepine (10 and 30 nM), a
selective muscarinic M1 receptor antagonist, antagonized acetylcholine (5 microM)
induced reduction of Vmax without affecting other effects of acetylcholine. In
addition, pirenzepine (30 nM) induced an immediate and linear acceleration of the
VmaX reduced by acetylcholine. In contrast, AF-DX 116 (11(?2-[(diethylamino)
methyl]-1-piperidyl?acetyl)-5,11-dihydro-6 H-pyridol[2,3-b][1,4]benzodiazepine-6
one base, 30-300 nM), a selective muscarinic M2 receptor antagonist, failed to
antagonize acetylcholine-induced reduction of Vmax, but abolished its increase.
It antagonized the shortening of action potential duration, membrane
hyperpolarization and decreased the beating rate. McN-A-343 (4-(m-chlorophenyl
carbamoyloxy)-2-butynyltrimethylammonium chloride, 100 and 300 microM), a
muscarinic M1 receptor agonist, reduced Vmax and prolonged action potential
duration, while oxotremorine (100-300 nM), a muscarinic M2 receptor agonist,
evoked reverse effects. These results suggest that acetylcholine exerts a mixed
effect on Vmax, consisting of a reduction and a facilitation, possibly mediated
by concurrent activation of muscarinic M1 and M2 receptors, respectively, in
isolated right atria of mice.
PMID- 9652365
TI - Effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) on rat aorta smooth muscle.
AB - To characterise the pharmacological activity of 2,5-di-t-butyl-1,4
benzohydroquinone (BHQ) on vascular smooth muscle, the different effects of BHQ
on rat aorta were investigated under several experimental conditions. In aortic
rings at rest or depolarised with 80 mM K+ in the presence of 1 microM
nifedipine, BHQ evoked a slow tonic contraction which was antagonised by 1 mM
Ni2+. Depolarised rings contracted in response to addition of 1 mM Ca2+, with an
EC50 value of 32.4+/-1.0 mM for K+. At 20 mM K+, Ca2+-induced contraction was
enhanced by BHQ. This effect was antagonised by 1 mM Ni2+, but not by 1 microM
nifedipine. By contrast, at 40, 80 and 128 mM K+, BHQ antagonised Ca2+-induced
contraction. This effect was partially reversed by 1 microM methyl-1,4-dihydro
2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyri dine-5-carboxylate (Bay K
8644) or by increasing extracellular Ca2+ concentration. In the presence of
nifedipine and Ni2+, depolarised rings (80 mM K+) contracted in response to
addition of 1 microM phenylephrine; this response was fast and then slowly
decreased. When the preparations were preincubated with BHQ, the phenylephrine
induced contraction was transient and antagonised in a concentration-dependent
manner by BHQ. These results indicate that the myotonic effect of BHQ on rat
aortic rings depends on activation of Ca2+ influx via a Ni2+-sensitive pathway,
whereas its myolytic activity is due either to antagonism of Ca2+ entry via L
type Ca2+ channels or depletion of intracellular Ca2+ stores.
PMID- 9652366
TI - Comparison of the antiarrhythmic and the proarrhythmic effect of almokalant in
anaesthetised rabbits.
AB - In this study the antiarrhythmic and the proarrhythmic activities of almokalant,
a selective class III antiarrhythmic agent, were compared. The antiarrhythmic
effect of the drug was tested in pentobarbital-anaesthetised rabbits. Arrhythmia
was evoked by occluding and releasing the left circumflex coronary artery.
Almokalant in a dose of 250 nmol/kg i.v., significantly decreased the incidence
of reperfusion induced ventricular fibrillation (21% vs. 75% in the control
group) and increased the proportion of surviving animals during reperfusion (86%
vs. 42%). The proarrhythmic effect of almokalant was examined during alpha1
adrenoceptor stimulation in chloralose-anaesthetised rabbits. Almokalant (75
nmol/kg per min) triggered torsade de pointes arrhythmias in 8 animals out of 11.
The dose of almokalant (mean+/-S.E.M.) required to produce this effect was 1181+/
519 nmol/kg. It is concluded that, although almokalant is an effective
antiarrhythmic agent against ischaemia-reperfusion induced arrhythmias, it has
marked proarrhythmic activity during alpha1-adrenoceptor stimulation.
PMID- 9652367
TI - Effects of K+ channel inhibitors on the basal tone and KCl- or methacholine
induced contraction of mouse trachea.
AB - The present study examined the effects of K+ channel inhibitors on the basal tone
and on KCl- or methacholine-induced contraction of the mouse-isolated trachea.
Glibenclamide and iberiotoxin, procaine, quinine and tetraethylammonium did not
induce any contraction of the indomethacin-treated mouse trachea. 4-Aminopyridine
induced concentration-dependent contraction. This action of 4-aminopyridine was
abolished by atropine and reduced by tetrodotoxin and nifedipine. Glibenclamide
failed to modify KCl- or methacholine-induced contraction. Iberiotoxin and 4
aminopyridine potentiated KCl- and methacholine-induced contractions. Nifedipine,
procaine, quinine and tetraethylammonium inhibited KCl- and methacholine-induced
contractions. These data suggest that the closure of large Ca2+-dependent K+
channels can potentiate KCI- and methacholine-induced contraction. The effects of
4-aminopyridine on the mouse trachea reflect chiefly activation of muscarinic
receptors. Procaine, quinine and tetraethylammonium inhibit depolarization
induced and receptor-mediated contractions of the mouse-isolated trachea.
PMID- 9652368
TI - WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but
not prolactin secretion.
AB - Previous studies suggest that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin,
adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin.
However, the lack of selective 5-HT1A receptor antagonists made it difficult to
confirm that 5-HT1A receptors mediate the neuroendocrine responses to 8-OH-DPAT.
This study investigated the effects of increasing doses of a selective 5-HT1A
receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses
induced by the 5-HT1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT,
500 microg/kg s.c., increased plasma levels of oxytocin (to 970% above basal
levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal
levels) and prolactin (to 313% above basal levels), but not renin. The lowest
dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced
increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1
mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and
maximally inhibited the corticosterone response to 8-OH-DPAT, although
corticosterone levels were still above basal. In contrast, the increase in
prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY
100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin
levels were markedly elevated (1550%) and administration of 8-OH-DPAT
significantly elevated plasma renin concentration. Taken together, these data
indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but
not prolactin secretion via activation of 5-HT1A receptors and (2) blockade of 5
HT1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT1A
receptor mechanisms.
PMID- 9652369
TI - The involvement of nitric oxide in stress-impaired testicular steroidogenesis.
AB - The participation of the nitric oxide (NO) pathway in downregulation of
testicular steroidogenesis in normal and stressed rats was investigated both in
vivo and in vitro. In Leydig cells from normal animals, isosorbide dinitrate, an
NO donor, decreased the human chorionic gonadotropin (CG)-stimulated and
progesterone-derived androgen production. Also, the intratesticular injection of
a precursor of NO, arginine (10 mg/testis), transiently decreased serum androgen
levels and inhibited human CG-stimulated androgen production in acute testicular
cultures. These effects were eliminated in rats cotreated with Nomega-nitro-L
arginine methyl ester (L-NAME) (2 X 600 microg/each testis). Acute immobilization
stress (2 h) decreased serum androgen levels and inhibited human CG-stimulated
androgen production in vitro. These effects were accompanied by a significant
increase in nitrite, a stable oxidation product of NO, in testicular cultures.
Bilateral intratesticular injection of L-NAME prevented the stress-induced
decrease of human CG-stimulated androgen production, and significantly reduced
the nitrite levels. These results implicate NO in normal and stress-impaired
testicular steroidogenesis.
PMID- 9652370
TI - L-arginine and NG-nitro-L-arginine methyl ester cause macromolecule extravasation
in the microcirculation of awake hamsters.
AB - We investigated the effects of L-arginine and NG-nitro-L-arginine methyl ester (L
NAME) on macromolecule extravasation in the microcirculation of awake hamsters by
computer-assisted image analysis of the distribution of FITC (fluorescein
isothiocyanate)-dextran fluorescence in dorsal fold skin preparations. This
analysis made it possible to simultaneously study the time course of local (skin)
and general (all irrigated organs) extravasation in 180-min experiments. Bolus
injection of 30 or 150 mg/kg (i.v.) L-arginine induced immediate local and
general macromolecule leakage and delayed venule dilation beginning 1 h later.
Injection of 20 or 100 mg/kg (i.v.) L-NAME caused rapid venule constriction
followed by local and general extravasation beginning 45-60 min later. These
effects of L-arginine and L-NAME were not mimicked by their biologically inactive
isomers, D-arginine and D-NAME. Simultaneous bolus injection of 20 mg/kg L-NAME
and 150 mg/kg L-arginine caused no significant change in fluorescence
distribution or venule diameter. L-arginine effects on macromolecule
extravasation were mimicked by sodium nitroprusside (10 microg/kg, i.v.) and by 8
bromo-cGMP (1 mg/kg, i.v.). Sodium nitroprusside was ineffective on venule
diameter. The effects of both L-arginine and sodium nitroprusside on FITC-dextran
extravasation were prevented by simultaneous injection (10 microg/kg, i.v.) of
the specific inhibitor of the soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3
a]quinoxalin-1-one (ODQ). This dose of ODQ mimicked the effects of L-NAME on
macromolecule extravasation and venule diameter. Taken together, these results
suggest that activation or inhibition of basal NO synthesis might induce
macromolecule leakage in the microcirculation of awake hamsters via temporally
distinct cGMP-dependent mechanisms.
PMID- 9652371
TI - Tetracycline inhibits the nitric oxide synthase activity induced by endotoxin in
cultured murine macrophages.
AB - Here we investigate the effects of tetracycline base and of a semi-synthetic
tetracycline derivative, doxycycline, on the induction of inducible nitric oxide
synthase and, hence, on the production of nitric oxide (NO) by lipopolysaccharide
in J774 macrophage cultured in vitro. The treatment of J774 line with
tetracycline base (6.25-250 microM) or doxycycline (5-50 microM) dose-dependently
decreased the lipopolysaccharide-stimulated (1 microg/ml) inducible NO synthase
activity and, consequently, nitrite formation. For instance, the inhibition was
70% for tetracycline base at 250 microM and 68% for doxycycline at 50 microM. The
inhibitory effect of tetracyclines was due neither to a reduction in the
viability of the cells, studied as colorimetric 3-[4,5-dimethylthiazol-2yl]-2,5
diphenyltetrazolium bromide (MTT) reduction assay, nor to an indiscriminate
inhibition of total protein synthesis, but to a specific decrease in inducible NO
synthase protein content in the cells, as attested by the significant reduction
of the expression of inducible NO synthase, assayed by sodium-dodecyl sulphate
polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. However, no
effect of tetracyclines on inducible NO synthase mRNA accumulation could be
demonstrated in lipopolysaccharide-stimulated macrophage line, suggesting that
the inhibitory effect of tetracyclines on NO synthesis involves post
transcriptional events. The reduction in lipopolysaccharide-stimulated nitrite
accumulation produced by tetracyclines was significantly less when they were
applied 6 h after lipopolysaccharide and absent 12 h after lipopolysaccharide,
indicating that tetracyclines modify an early event in inducible NO synthase
activation operating after mRNA transcription. The findings presented in this
study indicate that the modulation of NO synthesis is another possible pathway by
which tetracyclines may function as anti-inflammatory compounds.
PMID- 9652372
TI - Cloning, sequencing and functional expression of a guinea pig lung bradykinin B2
receptor.
AB - Kinin receptors are classified as B1 and B2 based upon agonist and antagonist
potencies and cloning and expression studies. Using sequences from human and rat
bradykinin B2 receptors, polymerase chain reaction (PCR) was utilized to isolate
cDNA from guinea pig lung. The receptor obtained is predicted to have 372 amino
acids and shares > 80% sequence homology with human, rat, rabbit and mouse B2
receptors. In competition binding experiments in Chinese hamster ovary (CHO-K1)
cells in which the guinea pig cDNA was expressed, [3H]bradykinin was displaced by
kinin receptor ligands with an order of potency consistent with a B2 subtype. In
CHO cells expressing the guinea pig receptor, bradykinin caused a concentration
45Ca2+ efflux. A B1 receptor agonist, desArg9-bradykinin, also caused 45Ca2+
efflux but with a potency several orders of magnitude lower than bradykinin.
Curiously, several B1 and B2 receptor antagonists induced 45Ca2+ efflux,
indicating that this receptor may be coupled differently in CHO cells than in
native tissues.
PMID- 9652373
TI - Interactions of ligands with active and inactive conformations of the dopamine D2
receptor.
AB - The affinities of 19 pharmacologically diverse dopamine D2 receptor ligands were
determined for the active and inactive conformations of cloned human dopamine D2
receptors expressed in Ltk cells. The agonist [3H]quinpirole was used to
selectively label the guanine nucleotide-binding protein-coupled, active receptor
conformation. The antagonist [3H]raclopride, in the presence of the non
hydrolysable GTP-analogue Gpp(NH)p and sodium ions and in the absence of
magnesium ions, was used to label the free inactive receptor conformation. The
intrinsic activities of the ligands were determined in a forskolin-stimulated
cyclic AMP assay using the same cells. An excellent correlation was shown between
the affinity ratios (KR/KRG) of the ligands for the two receptor conformations
and their intrinsic activity (r=0.96). The ligands included eight structurally
related and enantiopure 2-aminotetralin derivatives; the enantiomers of 5-hydroxy
2-(dipropylamino)tetralin, 5-methoxy-2-(dipropylamino)tetralin, 5-fluoro-2
(dipropylamino)tetralin and 2-(dipropylamino)tetralin. The (S)-enantiomers
behaved as full agonists in the cyclic AMP assay and displayed a large KR/KRG
ratio. The (R)-enantiomers were classified as partial agonists and had lower
ratios. The structure-affinity relationships of these compounds at the active and
the inactive receptor conformations were analysed separately, and used in
conjunction with a homology based receptor model of the dopamine D2 receptor.
This led to proposed binding modes for agonists, antagonists and partial agonists
in the 2-aminotetralin series. The concepts used in this study should be of value
in the design of ligands with predetermined affinity and intrinsic activity.
PMID- 9652374
TI - Inhibition by taurine of the inwardly rectifying K+ current in guinea pig
ventricular cardiomyocytes.
AB - Effects of taurine on the inwardly rectifying K+ current (IK1) in isolated guinea
pig ventricular cardiomyocytes were examined using patch voltage-clamp methods.
All experiments were performed at 36 degrees C. Taurine (10-20 mM) increased the
action potential duration, but failed to affect the resting potential. Holding
potential was maintained at -30 mV. The current was activated with an inwardly
going rectification, and was completely blocked by Ba2+ (2 mM). Taurine inhibited
IK1 at - 120 mV by 28.3+/-1.1% (n=6, P < 0.05) at 10 mM and by 36.0+/-2.1% (n=6,
P < 0.01) at 20 mM. The reversal potential was shifted in the hyperpolarizing
direction by 3.7+/-0.6 mV (n=6) at 20 mM. In inside-out patch-clamp experiments,
the amplitude of unitary channels was -2.7+/-0.3 pA (n=21) at -90 mV. Symmetrical
high-K+ (150 mM) solutions in both bath and pipette were used. The channel
conductance was 32+/-2 pS (n=9). Taurine did not affect channel conductance, but
markedly decreased the open probability at - 120 mV of channel by 21.5+/-2.4%
(n=8, P < 0.01) at 10 mM, and by 56.7+/-3.8% (n=8, P < 0.001) at 20 mM. These
responses were almost reversible. These results suggest that taurine directly
modulates the open probability of the inwardly rectifying K+ current, resulting
in regulation of the functions of heart cells.
PMID- 9652375
TI - Relationship between cytotoxic drug response patterns and activity of drug efflux
transporters mediating multidrug resistance.
AB - Drug activity patterns in 10 human tumor cell lines representing defined
mechanisms of drug resistance, including cell lines with high expression of P
glycoprotein and multidrug resistance associated protein (MRP), have previously
been used for prediction of mechanism of drug action. In the present study, this
cell line panel was analyzed for cellular accumulation of the fluorescent probe
calcein/AM [4'5'-bis(N,N-bis (carboxymethyl) aminomethyl) fluorescein
acetoxymethyl ester] and compared with drug response patterns of 20 standard
chemotherapeutic drugs. According to degree of correlation with the ability to
exclude calcein/AM, topoisomerase II inhibitors and tubulin actives were at the
top of the list although the correlations were of lower magnitude than those
obtained from the drug response patterns of mechanistically similar drugs. There
was a significant relationship between the rank-order of drugs based on
correlation with calcein/AM accumulation and Pgp/MRP mediated drug resistance
suggesting that compounds being substrates for these pumps were identified. In
simulated drug response profiles, the impact of Pgp and MRP expressing cell lines
on the mechanistic prediction was found to be marginal. The results indicate that
the differential molecular function/expression in the cell line panel may
identify drugs interacting with specific biochemical pathways. Furthermore, the
presence of cell lines overexpressing drug efflux mechanisms in the panel do not
significantly influence the mechanistic predictions.
PMID- 9652377
TI - Sulpiride, but not haloperidol, up-regulates gamma-hydroxybutyrate receptors in
vivo and in cultured cells.
AB - Five days of gamma-hydroxybutyrate (GHB) administration (3 x 500 mg kg(-1) day(
1) i.p.) to rats resulted in a significant decrease in the density of GHB
receptors measured in the whole rat brain without modification of their
corresponding affinity. Similar administration of (-)-sulpiride (2 X 100 mg kg(
1) day(-1) i.p. for 5 days) induces an up-regulation of GHB receptors without
change in their dissociation constants (Kd). Haloperidol (2 X 2 mg day(-1) i.p.
for 5 days) showed no effect. Administered chronically via osmotic minipumps
directly into the lateral ventricles, (-)-sulpiride (60 microg day(-1) for 7
days) and GHB (600 microg day(-1) for 7 days) up-regulated and down-regulated rat
brain GHB receptors, respectively. Finally, in a mouse hybridoma cell line (NCB
20 cells) expressing GHB receptors, the treatment of these cells with 1 mM GHB,
100 microM (-)-sulpiride or 1 mM GABA decreases, increases and induces no change,
respectively, in the density of GHB receptors after 3 days of treatments. These
results indicate that chronic GHB treatment modifies the expression of its
receptor and that sulpiride also induces plastic changes in GHB receptors perhaps
via antagonistic properties.
PMID- 9652376
TI - Muscarinic cation current and suppression of Ca2+ current in guinea pig ileal
smooth muscle cells.
AB - Cationic current (Icat) and inhibition of the voltage-dependent Ca2+ current
(ICa) evoked by muscarinic receptor activation with carbachol were studied using
whole-cell patch clamp technique in smooth muscle cells isolated from
longitudinal muscle of guinea pig small intestine. With low buffering of [Ca2+]i
(0.1 mM BAPTA [1,2-bis-(2-aminophenoxy)-ethane-N,N, N', N'-tetraacetic acid] in
pipette solution) Icat and ICa inhibitory responses had a rapid onset to an
initial peak followed by a sustained phase. The sustained phase of ICa
suppression was bigger than in the case when [Ca2+]i was clamped to 100 nM, but
decreased with repeated stimulation. Upon repeated stimulation with 50 microM
carbachol in cells where [Ca2+]i was clamped to 100 nM and when GTP was absent,
Icat amplitude decreased strongly and more substantially compared to ICa
inhibition, but both responses declined only slightly when 1 mM GTP was present
in the pipette solution. GDP-betaS (1 or 5 mM) in pipette solution or pre
treatment of cells with pertussis toxin (6 microg/ml, for 4 h or longer) blocked
Icat more than ICa suppression by carbachol, whereas L-NAME (N-omega-nitro-L
arginine methyl ester hydrochloride) (100 microM in pipette solution) affected
neither of them significantly. We conclude that the cationic current and the
suppression of the voltage-dependent Ca2+ current evoked by muscarinic receptor
activation are mediated by pertussis toxin-sensitive G-protein(s) but the latter
response was less sensitive to blockade by GDP-betaS and to GTP deficiency in the
cell.
PMID- 9652378
TI - Effect of adenosine receptor agonists on release of the nucleoside analogue
[3H]formycin B from cultured smooth muscle DDT1 MF-2 cells.
AB - Adenosine has receptor-mediated effects in a variety of cell types and is
predominantly formed from ATP by a series of nucleotidase reactions. Adenosine
formed intracellularly can be released by bidirectional nucleoside transport
processes to activate cell surface receptors. We examined whether stimulation of
adenosine receptors has a regulatory effect on transporter-mediated nucleoside
release. DDT1 MF-2 smooth muscle cells, which possess nitrobenzylthioinosine
sensitive (ES) transporters as well as both adenosine A1 and A2 receptors, were
loaded with the metabolically stable nucleoside analogue [3H]formycin B. N6
cyclohexyladenosine (CHA), a selective adenosine A1 receptor agonist, produced a
concentration-dependent inhibition of [3H]formycin B release with an IC50 value
of 2.7 microM. Further investigation revealed CHA interacts directly with
nucleoside transporters with a Ki value of 3.3 microM. Neither 5'-N
ethylcarboxamidoadenosine (NECA), a mixed adenosine A1 and A2 receptor agonist,
nor CGS 21680, a selective adenosine A2A receptor agonist, affected nucleoside
release. We conclude that release of the nucleoside formycin B from DDT1 MF-2
cells is not regulated by adenosine A1 or A2 receptor activation.
PMID- 9652379
TI - U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream
of phospholipase C in CHO cells.
AB - The aminosteroid 1-(6-?[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]
amino?hexyl)- 1H-pyrrole-2,5-dione (U73122) and its inactive analogue 1-(6
?[17beta-3-methoxyestra-1,3,5(10)-trien- 17-yl]-amino?hexyl-2,5-pyrrolidine-dione
(U73343) are widely used to study the involvement of G protein-coupled 1
phosphatidylinositol-phosphodiesterase, or phospholipase C, in receptor-mediated
cell activation. The present work shows that both aminosteroids inhibit
cholecystokinin-(26-33)-peptide amide (CCK-8)-induced phospholipase D activation
equipotently in Chinese hamster ovary cells expressing the cholecystokinin-A
receptor (CHO-CCK(A) cells). In addition, the two aminosteroids virtually
completely inhibited thapsigargin- and 12-O-tetradecanoylphorbol 13-acetate (TPA)
induced phospholipase D activation. Since the latter two drugs mimic inositol
1,4,5-trisphosphate-mediated Ca2+ mobilisation and 1,2-diacylglycerol-mediated
protein kinase C activation. respectively, this suggests that both U73122 and
U73343 act downstream of phospholipase C to inhibit receptor-mediated
phospholipase D activation. U73122, but not U73343. effectively inhibited both
TPA/Ca2+-stimulated phospholipase D activation and TPA/phosphatidylserine
stimulated protein kinase C activation in a homogenate of CHO-CCK(A) cells. The
data presented suggest that U73122 may act at the level of protein kinase C to
inhibit activation of phospholipase D. The exact site of action of U73343 is
presently unknown.
PMID- 9652380
TI - Toxoplasmosis of rats: a review, with considerations of their value as an animal
model and their possible role in epidemiology.
AB - We critically review and summarize information on the prevalence of Toxoplasma
gondii infections in rats, mainly Rattus norvegicus, and their possible role as a
source of infection for larger carnivores and omnivores. We also review
information on immunology and natural resistance, contributing to the model value
of rats in the analysis of human infection. Rats can be successfully infected
with oocysts (sporozoites), tissue cysts (bradyzoites), and tachyzoites. Even
adult rats, that are resistant to clinical toxoplasmosis, can be infected orally
with a few oocysts or tissue cysts. Infections with tachyzoites of the RH strain
are highly variable. Congenital transmission of T. gondii occurs at a high rate
when rats are infected during pregnancy. Congenitally infected rats can harbor
viable T. gondii in the absence of detectable antibodies to T. gondii and rats
with low antibody titers may harbor few or no organisms. The isolation of viable
T. gondii by bioassay is the only reliable means to determine persistence of
chronic T. gondii infection in feral rats. No evidence was found for maintenance
of T. gondii in rats by vertical transmission in the absence of cats.
PMID- 9652381
TI - Oocysts of Cryptosporidium from snakes are not infectious to ducklings but retain
viability after intestinal passage through a refractory host.
AB - Six 2-week-old Cryptosporidium-free Peking ducklings (Anas platyrhynchos) each
received 2.0 x 10(6) viable Cryptosporidium serpentis oocysts from 6 naturally
infected captive snakes. Histological sections of digestive (stomach, jejunum,
ileum, cloaca, and cecum) and respiratory tract tissues (larynx, trachea, and
lungs) did not contain life-cycle stages of Cryptosporidium in any of the
inoculated ducklings. Because ducklings were refractory to infection, C.
serpentis transmission via a diet of Peking ducklings is improbable. Viable (per
in vitro excystation assay) inoculum-derived oocysts were detected in duckling
feces up to 7 days post-inoculation (PI); the number of intact oocysts excreted
during the first 2 days PI was significantly higher than for the remaining 5 days
PI (P < 0.01). The dynamics of oocyst shedding showed that overall the birds
released a significantly higher number of intact oocysts than oocyst shells (P <
0.01). Retention of the viability of C. serpentis oocysts following intestinal
passage through a refractory avian species may have epizootiological
implications. Under certain circumstances such as after the ingestion of C.
serpentis-infected prey, herpetivorous birds may disseminate C. serpentis oocysts
in the environment.
PMID- 9652382
TI - Immunization against East Coast Fever in field cattle with low infectivity
Theileria parva stabilate--preliminary assessment.
AB - Two Theileria parva sporozoite stabilates stored at -196 degrees C, then at -70
degrees C for six weeks (stabilate 1) and more than six months (stabilate 2) were
inoculated into four eight-month old male calves, 1 and 2 (stabilate 1), and 3
and 4 (stabilate 2). Calves 1 and 2 developed pyrexia, enlargement of lymph
nodes, and the former died of East Coast Fever. Calves 3 and 4 showed slight
enlargement of lymph nodes without fever. Lymph node smears from all calves (from
day 10 to 20 post-inoculation) showed lymphoblasts, phagocytic macrophages, and
schizonts. Piroplasms were detected in erythrocytes in blood smears from calves 1
and 2 but not in calves 3 and 4. Calves 2, 3 and 4 recovered without any
treatment while calf 1 died of East Coast Fever on day 20. Serum samples from
recovered calves taken on day 30 of the experiment were positive for antischizont
antibodies to T. parva at 1:640 dilution, but pre-inoculation serum samples were
negative. Stabilate 2 was used to immunize 64 Boran, Friesian, Ayrshire and
crosses with Zebu cattle in four herds with 25% reduction of oxytetracycline
dose. All the animals except one calf recovered without any severe reactions. The
latter died of disease other than ECF after the monitoring period was over (day
24). Day 30 post-inoculation serum samples were positive for T. parva
antischizont antibodies. A follow-up of the remaining animals for over one year
revealed no further ECF incidences in these herds. This experiment shows the loss
of infectivity of the vaccine stored at temperatures higher than -196 degrees C.
dependent on the duration. However, despite the lack of clinical signs in calves
3 and 4, there was cellular response and antibody production, and the stabilate
for vaccine against East Coast fever can thus be stored prior to use at higher
than -196 degrees C and still maintain capability to produce antibodies in field
cattle, eliminating the use of oxytetracycline and monitoring. The vaccine will
be cheaper and easier to use and the requirement for liquid nitrogen in the field
reduced and the scale of application of the vaccine widened.
PMID- 9652383
TI - Hypobiosis of Haemonchus contortus in natural infections of sheep and goats in a
semi-arid area of Kenya.
AB - A total of 42 lambs, 42 kids, 21 ewes and 21 does were necropsied during an
investigation of the epidemiology of Haemonchus contortus infection of sheep (Red
Maasai) and goats (Small East African Goat) in a semi-arid area of Kenya.
Availability and establishment of the infective stages were monitored by the
necropsy of 21 tracer lambs and 21 tracer kids. Prevalence of H. contortus was
over 90% in both sheep and goats and this species contributed to about 80% of the
total worm burden. Only about 10% of the hypobiotic larvae were recovered from
the mucosal digest whereas about 90% were recovered from the abomasal contents
and washings, thereby suggesting that hypobiotic larvae may be loosely attached
to the abomasal mucosa from which they may be dislodged during the processing of
the abomasa for examination. Throughout the study, both adult worms and
hypobiotic larvae were found in proportions that varied with seasons.
Statistically, a higher proportion of hypobiotic larvae was found during the dry
months than during the wet months, an indication that hypobiosis was an important
feature in the survival of H. contortus during the dry months. Negligible worm
burdens were acquired by the tracers during the short rains, suggesting that few
H. contortus larvae survived on pasture in this season. The effectiveness of
strategic control using ivermectin varied according to the timing in relation to
the wet season. Treatment did not influence the seasonal pattern of hypobiosis
but the treatment administered before the onset of the rains significantly
reduced the numbers of both hypobiotic larvae and the adult worms. Treatment
during the rains conferred a temporary relief of adult worm burden but had no
impact on hypobiotic larvae.
PMID- 9652384
TI - Breed-associated resistance to tick infestation in Bos indicus and their crosses
with Bos taurus.
AB - The relative resistance to tick infestation of zebu (Bos indicus) in comparison
to crossbred (B. indicus x B. taurus) cattle was investigated. B. indicus breeds,
all belonging to Tanganyika shorthorn zebu were Meru, Mbullu and Iringa red.
Crossbreds were Meru x Friesian and Iringa red x Friesian. Parameters to
distinguish between 'tick resistant' and 'tick susceptible' cattle were tick
counts on naturally exposed animals, serum complement levels and delayed skin
hypersensitivity response to phytohaemagglutinin. Results have shown that pure
zebu cattle are less infested with ticks when compared to zebu-taurine crosses
under identical field conditions. Zebu cattle also had significantly higher serum
complement level than crossbred cattle. While serum complement and tick burden
were negatively associated (r = -0.27, P < 0.001), the cutaneous response to
phytohaemagglutinin did not vary with tick infestation. The influence of cattle
breed on tick infestation and serum complement level is demonstrated.
PMID- 9652385
TI - Failure of buparvaquone (Butalex) in the treatment of canine visceral
leishmaniosis.
AB - Buparvaquone (Butalex), a therapeutic for theileriosis, has been shown to have
anti-leishmanial activity in vitro. Seven dogs with symptomatic,
parasitologically positive, canine visceral leishmaniosis were treated with
Butalex at 5 mg kg(-1) body weight using four doses over 12 days. Two animals
showed minor clinical improvement (growth of healthy hair) but all remained
parasitologically positive and disease progression was not halted.
PMID- 9652386
TI - Protein translocation into the endoplasmic reticulum (ER)--two similar routes
with different modes.
AB - Protein translocation into the endoplasmic reticulum (ER) occurs
cotranslationally with the ribosome tightly bound at the membrane, or post
translationally. Transport of polypeptides is performed by an elaborate structure
in the ER membrane consisting of numerous proteins. Both pathways have been
reconstituted in vitro using proteoliposomes that contain purified components.
Primary structures of these key components have been identified and recent
electron microscopic data provide a first impression of the tertiary structure of
the translocation apparatus. However, the precise function of most subunits of
the translocation apparatus is still a mystery and little is known about
structural changes in the translocation site during a transport cycle.
PMID- 9652387
TI - Secretion of tetrain, a Tetrahymena cysteine protease, as a mature enzyme and its
identification as a member of the cathepsin L subfamily.
AB - A protease in the culture medium of Tetrahymena pyriformis was purified to
homogeneity. The purified protease had an apparent molecular mass of 28 kDa on
SDS/PAGE. The amino acid sequences of the N-terminal and internal peptides of the
protease showed complete identity with those of tetrain, an enzyme previously
reported as a Tetrahymena cysteine protease but not characterized in detail. Two
overlapping cDNA clones for tetrain were sequenced, and the nucleotide sequence
predicts that these clones encode a 330-amino acid protein composed of a 16
residue N-terminal signal sequence followed by a 103-residue propeptide and a 211
residue mature protease. The primary structure and enzymatic properties support
the conclusion that tetrain belongs to the cathepsin L subfamily. Immunoblotting
analyses showed that mature tetrain was found exclusively in the culture medium.
Immunofluorescence microscopy demonstrated that tetrain was concentrated in or
around the food vacuoles of cells in the late logarithmic phase, but the staining
of food vacuoles was not obvious in the stationary phase. These results suggest
that tetrain is synthesized at the logarithmic phase and is secreted into the
culture medium as a mature form.
PMID- 9652388
TI - The Ulip family phosphoproteins--common and specific properties.
AB - The search for intracellular phosphoproteins implicated in the regulation of
neuronal differentiation led to the identification of Ulip1, a mammalian protein
related to the Caenorhabditis elegans unc-33 gene product [Byk, T., Dobransky,
T., Cifuentes-Diaz, C. & Sobel, A. (1996) J. Neurosc. 16, 688-701]. The
expression level and phosphorylation pattern of Ulip1 were shown to be strongly
regulated during development and neuronal differentiation. We have isolated three
additional complete coding sequences for members of the Ulip family in the mouse,
Ulips 2-4, all preferentially expressed in the nervous system. Furthermore, two
Ulip sequences, Ulips A and Ulips B, could be identified in C. elegans. The Ulip
family is highly conserved throughout evolution (more than 96 % for Ulips 1-3 and
92.5 % for Ulip4 between mouse and human) and the various members of the family
within a single species display about 75% similarity. Sequence comparisons
further reveal several highly similar domains and subdomains, including a 32
amino-acid region highly conserved from a bacterial hydantoinase to human Ulips.
Two-dimensional immunoblot analysis of in vitro translated Ulips 1-4 demonstrates
the existence, for each Ulip protein, of several, most probably differentially
phosphorylated forms, in agreement with the presence of conserved phosphorylation
consensus sites within their sequences. The expression of Ulips 1-4 mRNAs is
differentially regulated during development and nerve-growth-factor-induced
neuronal differentiation of PC12 cells. Our results indicate a differential,
possibly complementary role of phosphoproteins of the highly conserved Ulip
family in the control of neuronal differentiation, in relation with the
development and plasticity of the nervous system.
PMID- 9652389
TI - Contribution to first-pass metabolism of ethanol and inhibition by ethanol for
retinol oxidation in human alcohol dehydrogenase family--implications for
etiology of fetal alcohol syndrome and alcohol-related diseases.
AB - The alcohol dehydrogenase (ADH) family is involved in the metabolism of both
ethanol and retinoids. To quantitatively assess the potential contributions to
first-pass metabolism of ethanol and the ethanol interference with retinoid
homeostasis, saturation kinetics for ethanol oxidation as well as inhibition
kinetics by ethanol for all-trans-retinol oxidation of human class I alpha alpha,
beta1beta1, beta2beta2, gamma1gamma1, class II pi pi, class III chi chi, and
class IV mu mu were evaluated and compared. Class I and class II ADHs exhibited
substrate inhibition with inhibition constants ranging over 250-720 mM (except
gamma1gamma1) ethanol. Class IV ADH displayed no appreciable inhibition up to 1 M
ethanol. Activity of the class III enzyme (190 nM subunit) was undetectable at
250 mM ethanol. The kinetic simulations indicate that the hepatic pi pi and the
gastric mu mu can most effectively contribute to first-pass metabolism of
alcohol. The Michaelis constant (Km), turnover number (k(cat)), and catalytic
efficiency (k(cat)/Km) for retinol oxidation relative to that for ethanol
oxidation in class I, class II, and class IV ADHs ranged over 0.00022-1.3, 0.071
0.48, and 0.24-650, respectively. Ethanol was a competitive inhibitor against
retinol for class I, II, and IV ADHs with apparent inhibition constants ranging
over 0.037-11 mM, indicating that retinoic acid synthesis through the ADH
pathways can be tremendously blocked during social/heavy drinking. These findings
support the notion that first-pass metabolism of alcohol may occur mainly in the
liver through class II pi pi and that cellular retinoid signaling may be
perturbed by ethanol via ADH pathways.
PMID- 9652390
TI - The defense-related rice gene Pir7b encodes an alpha/beta hydrolase fold protein
exhibiting esterase activity towards naphthol AS-esters.
AB - Acquired resistance of rice to Pyricularia oryzae, the causing agent of rice
blast, can be induced by inoculation with the non-host pathogen Pseudomonas
syringae pv. syringae. We have previously cloned a cDNA and a corresponding gene
(Pir7b) whose transcripts accumulate upon infiltration with the resistance
inducing bacteria. The putative encoded product Pir7b exhibits significant
sequence similarity to two recently cloned hydroxynitrile lyases from Manihot
esculenta (cassava) and Hevea brasisliensis, enzymes involved in the release of
hydrogen cyanide from cyanogenic glycosides. As rice does not contain cyanogenic
glycosides, a similar function of Pir7b appears unplausible. In order to
functionally characterize the protein, recombinant Pir7b was produced in
Escherichia coli and Saccharomyces cerevisiae. We show that recombinant Pir7b
does not have hydroxynitrile lyase activity, but exhibits esterase activity
towards naphthol AS-acetate. Using Pir7b-specific antibodies, we show that the
protein accumulates in rice leaves inoculated with P. syringae pv. syringae. Both
the recombinant and the authentic proteins have an apparent molecular mass of 32
kDa (28.8 kDa calculated) and seem to be active as monomers. Pir7b esterase also
exhibits sequence similarity to several expressed sequence tags of Arabidopsis
thaliana, indicating that it belongs to a family of proteins widely occuring in
plants.
PMID- 9652391
TI - Blockage of apoptotic signaling of transforming growth factor-beta in human
hepatoma cells by carboxyfullerene.
AB - Transforming growth factor-beta (TGF-beta) has been shown to induce apoptosis in
normal hepatocytes and hepatoma cells both in vivo and in vitro. However, the
mechanism by which TGF-beta induces apoptosis is not clear. The antiapoptotic
activity of antioxidants including N-acetyl-L-cysteine (Ac-Cys), ascorbic acid
and a novel free radical scavenger, carboxyfullerene (C60) on TGF-beta-treated
human hepatoma Hep3B cells was examined. Only the water-soluble hexacarboxylic
acid derivative of C60 was found to prevent TGF-beta-induced apoptosis.
Antiapoptotic activity of C60 correlated its ability to eliminate TGF-beta
generated reactive oxygen species (ROSs). However, C60 did not interfere with TGF
beta-activated PAI-1 promoter activity in the Hep3B cells. These results indicate
that the signaling pathway of TGF-beta-induced apoptosis may be related to the
generation of ROSs and may be uncoupled from the TGF-beta-activated gene promoter
activity. Furthermore, the regioisomer of C60 with a C3 symmetry was more potent
in protecting cells from apoptosis than that with a D3 symmetry, and the C3
isomer had stronger interactions with lipid bilayers than the D3 isomer. The
spectroscopic analysis revealed that the C3 isomer had stronger interactions with
artificial lipid bilayers than the D3 isomer. Therefore, our study indicates that
C60 may interact with membrane to eliminate TGF-beta-induced ROSs and to prevent
apoptosis occur in human hepatoma cells.
PMID- 9652392
TI - A depressant insect-selective toxin analog from the venom of the scorpion Leiurus
quinquestriatus hebraeus--purification and structure/function characterization.
AB - The scorpion venom-derived excitatory and depressant insect-selective polypeptide
neurotoxins modify sodium conductance in insect neuronal membranes and differ
greatly in their primary structures and symptoms induced in blow fly larvae. We
report here the purification and characterization of a new insect selective
toxin, LqhIT5. LqhIT5 is more similar to the excitatory toxins in its mode of
action and the depressant toxins in its primary structure. This toxin is a single
polypeptide composed of 61 amino acids that are cross linked by four disulfide
bonds. When LqhIT5 is injected into blow fly larvae, a fast contraction paralysis
occurs without depressant activity. No mammalian toxicity was detected by
subcutaneous or intracranial injections of this toxin into mice. Sequence
comparison of LqhIT5 and known depressant toxins shows a high degree of
similarity among the amino acids located on the C-terminus of the toxins.
However, there are some clear differences in the amino acids located close to the
N-terminus of the toxins. By the aid of homology modeling, we demonstrated that
these amino acids have the same orientation in the tertiary structure of the
molecule and are exposed to the environment. The change in the mode of action of
LqhIT5 (no depressant activity) by substitutions of a few amino acids located on
a specific exposed area of the toxin shed a new light on the structure/function
relationship of scorpion toxins. These results caution that similarity in the
mechanism of action of scorpion toxins does not always follow from an overall
similarity in sequence.
PMID- 9652393
TI - In vitro activation of pro-phenol-oxidase by two kinds of pro-phenol-oxidase
activating factors isolated from hemolymph of coleopteran, Holotrichia diomphalia
larvae.
AB - Previously, we purified and characterized a pro-phenol-oxidase (pro-PO) of 79 kDa
from coleopteran insect, Holotrichia diomphalia larvae [Kwon et al. (1997) Mol.
Cells 7, 90-97]. Here, we describe the identification of two pro-PO-activating
factors (PPAF), named PPAF-I and PPAF-II, directly involved in the activation of
the isolated pro-PO. When pro-PO was incubated with either PPAF-I or PPAF-II, no
phenol oxidase activity was observed. However, incubation of pro-PO with both
PPAF-I and PPAF-II specifically exhibited phenol oxidase activity. The purified
PPAF-I with a molecular mass of 33 kDa on SDS/PAGE had characteristics of a
serine protease. It exhibited amidase activity against fluorogenic peptide
substrates, tert-butoxycarbonyl-phenylalanyl-seryl-arginyl-4-methylcoumaryl-7
amide being the best among the substrates examined. The activity was completely
inhibited by 0.02 mM p-nitrophenyl-p'-guanidinobenzoate HCl and
diisopropylflurophosphate. The NH2-terminal sequence of PPAF-I had significant
sequence similarity to those of serine proteases. On the other hand, the purified
PPAF-II had a molecular mass of 40 kDa on SDS/PAGE and 400 kDa determined by gel
filtration, indicating an oligomeric protein. The NH2-terminal sequence of PPAF
II showed no similarity to known proteins. PPAF-II exhibited no amidase activity
against the fluorogenic substrates. Reconstitution experiments and immunoblotting
analysis using affinity-purified antibody against pro-PO demonstrated that PPAF-I
first cleaves the intact pro-PO to an intermediate of 76 kDa with no phenol
oxidase activity, and then, PPAF-I converts the intermediate to the active phenol
oxidase of 60 kDa in the presence of PPAF-II. These results indicate that the
activation of pro-PO system in hemolymph of H. diomphalia larvae is accomplished
by at least two activating factors, a serine protease and a protein cofactor.
PMID- 9652394
TI - Structure of the O-antigen of Vibrio cholerae O155 that shares a putative D
galactose 4,6-cyclophosphate-associated epitope with V. cholerae O139 Bengal.
AB - The O-specific polysaccharide of Vibrio cholerae 0155 was studied by sugar and
methylation analyses, dephosphorylation with 48% hydrofluoric acid, 1H- and 13C
NMR spectroscopy, including two-dimensional COSY, TOCSY, NOESY, and heteronuclear
single-quantum coherence (HSQC) experiments. The following structure of the
pentasaccharide repeating unit of the polysaccharide was established:
carbohydrate sequence [see text]. An unusual component, D-galactose 4,6
cyclophosphate, has been reported previously as a component of the capsular
polysaccharide and O-antigen of V. cholerae O139 Bengal and appears to be
responsible for the known serological cross-reactivity between V. cholerae O139
and O155.
PMID- 9652395
TI - A pancreas-specific glycosylated protein disulphide-isomerase binds to misfolded
proteins and peptides with an interaction inhibited by oestrogens.
AB - Using a cross-linking approach, we have demonstrated that radiolabeled model
peptides or misfolded proteins specifically interact in vitro with two different
luminal proteins in a crude extract from sheep pancreas microsomes. One of the
proteins was identified as protein disulphide-isomerase (PDI), the other one was
a related protein (PDIp). We have shown that PDIp was expressed exclusively in
the pancreas. Interspecies conservation of PDIp was confirmed and, unlike other
members of the PDI family, PDIp from various sources was found to be a
glycoprotein. PDIp interacted with peptides and also a misfolded protein, but not
with native proteins, suggesting that it might act as a molecular chaperone. The
initial binding process was independent of the presence of Cys residues in the
probed peptides. Certain oestrogens strongly inhibited the interaction between
peptides and PDIp, with 17beta-oestradiol being the most potent inhibitor.
PMID- 9652396
TI - Transcriptional regulation of the rat glutamine synthetase gene by tumor necrosis
factor-alpha.
AB - The expression of glutamine synthetase (GS) is induced in rat skeletal muscle
cells (L-6) in response to treatment with the inflammatory cytokine tumor
necrosis factor alpha (TNF-alpha). This paper reports the regulation of GS
expression in rat skeletal muscle which expresses high levels of GS. TNF-alpha
treatment leads to a 3-4-fold increase in GS activity in a dose-dependent and
time-dependent manner. Northern-blot analysis of GS mRNA revealed an increased
mRNA concentration, reaching a peak at 12 h in response to TNF-alpha treatment.
To monitor transcriptional activation of GS by TNF-alpha, and to identify a TNF
alpha-responsive element in the GS promoter, L6 cells were treated with TNF-alpha
following transfection of GS-chloramphenicol-acetyltransferase (CAT) constructs.
The first 251-bp fragment at the GS upstream sequence showed basal promoter
activity, but failed to show any TNF-alpha-inducible activity. However, a 2.5-3
fold induction was noted in constructs extending up to 1.1 kb. This data
demonstrates that the rat GS gene is transcriptionally regulated by TNF-alpha and
identifies a TNF-alpha-responsive region at the 5' flanking sequence of the GS
gene.
PMID- 9652397
TI - The mitochondrial phosphoglyceroyl-ATP-containing polymer, purinogen, is
unchanged by cardiac ischaemia and reperfusion but may function in the regulation
of free intracellular inorganic phosphate concentrations.
AB - Previous work in our laboratory demonstrating large unexplained systematic
variations in the heart contents of free adenine nucleotides led us to propose
the existence of some unrecognised sequestered form and thence to the
purification of very labile acid-insoluble oligomers which we characterised as
oligo[3-phospho-glyceroyl-gamma-triphospho(5')adenosine(3')] , abbreviated to (PG
ATP)n. More recently, we provided evidence that these oligomers appear to be the
end chains of a complex polymer located in the mitochondrial intermembrane space
of a number of rat tissues. We called this polymer purinogen and devised a means
of assaying it quantitively [Patel, B., Sarcina, M. & Mowbray, J. (1994) Eur. J.
Biochem. 220, 663-669]. Here we report measurements of purinogen in perfused
hearts subjected to moderate and severe global ischaemia and reperfusion.
Measurements of tissue and perfusate nucleotides, nucleosides and purine
degradation products demonstrate that ischaemia led to the augmentation of the
free nucleotide content by up to 30% and its re-sequestration on reperfusion in
reversible but not in irreversible ischaemia. The purinogen content was unchanged
by ischaemia or reperfusion implying the existence of some other unidentified
storage pool. By contrast, glucose addition to glycolytically deprived hearts or
removal of Pi from perfusion medium, conditions which might be expected to alter
demand for intracellular Pi, led to the quantitative transfer of nucleotides
between phosphate-rich purinogen and free nucleotides. The possibility that
purinogen may act as a rapidly accessible reservoir of intracellular inorganic
phosphate is discussed.
PMID- 9652398
TI - Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor
kappaB (NF-kappaB) and kappaB-dependent transcription in epithelial cells.
AB - The production of inflammatory mediators by epithelial cells in inflammatory lung
diseases may represent an important target for the anti-inflammatory effects of
glucocorticoids. Nuclear factor-kappaB (NF-kappaB) is a major activator of
inflammatory genes and has been proposed as a target for inhibition by
glucocorticoids. We have used human pulmonary type-II A549 and airway epithelial
BEAS-2B cells to investigate the effect of glucocorticoids on NF-kappaB
regulation and kappaB-dependent transcription. In A549 cells following
interleukin-1beta (IL-1beta) treatment, there was no effect of dexamethasone on
the disappearance of I kappaB alpha protein, its subsequent reappearance 90-min
later or the rapid induction of I kappaB alpha mRNA and transcription rate.
Expression of p65 and p50/p105 proteins were also unaffected by dexamethasone. In
addition, the rapid IL-1beta-induction of NF-kappaB DNA binding and p65 nuclear
localisation was unaffected by short (1-6 hours) dexamethasone pre-treatments.
Similarly, BEAS-2B cells showed no effect of dexamethasone on IL-1beta-induced NF
kappaB (p50/p65). Stable transfection of a kappaB-dependent reporter in A549
cells resulted in an 8-9-fold activation by IL-1beta or phorbol ester, that was
repressed 30-40% by dexamethasone. However, in these cells, IL-1beta induction of
inducible nitric oxide synthase, granulocyte-macrophage colony stimulating factor
and cyclooxygenase-2 mRNA showed 70-90% repression by dexamethsone. We,
therefore, conclude that in these epithelial cells, the repressive effects of
glucocorticoids are not mediated by up-regulation of I kappaB alpha, decreased
p50/p65 gene expression or inhibition of NF-kappaB DNA binding. Furthermore,
since the maximal repression of IL-1beta or phorbol-ester-induced kappaB
dependent transcription by dexamethasone was less than 40%, simple inhibition of
kappaB-dependent transcription cannot by itself account for the full repressive
effects of glucocorticoids observed in these cells.
PMID- 9652399
TI - Cloning of two cDNAs encoding three small serine protease inhibiting peptides
from the desert locust Schistocerca gregaria and analysis of tissue-dependent and
stage-dependent expression.
AB - This study describes the cloning of two cDNAs encoding three serine-protease
inhibiting peptides, SGPI I, II and III, which were recently identified from
ovarian extracts of the desert locust, Schistocerca gregaria. The first cDNA
codes for the precursor polypeptides of SGPI I and SGPI II; the second encodes
only a single inhibitor, SGPI III. Northern-blot analysis revealed an approximate
length of 0.8 kb for SGPI-I/II mRNA and 0.6 kb for SGPI-III mRNA. The transcripts
are present in several locust tissues, but they could not be detected in the
midgut. The gene for SGPI-I/II is abundantly transcribed during all larval and
adult stages, whereas SGPI-III mRNA is mainly present in adults. Northern-blot
hybridization also revealed important changes in the SGPI-mRNA content during the
molting cycle and during the adult reproductive cycle. Moreover, a differential
hormonal control was observed in adult females which had been treated with
precocene, juvenile hormone or ecdysone.
PMID- 9652400
TI - Carbon-flux distribution in the central metabolic pathways of Corynebacterium
glutamicum during growth on fructose.
AB - Growth of Corynebacterium glutamicum on fructose was significantly less than that
obtained on glucose, despite similar rates of substrate uptake. This was in part
due to the production of overflow metabolites (dihydroxyacetone and lactate) but
also to the increased production of CO2 during growth on fructose. These
differences in carbon-metabolite accumulation are indicative of a different
pattern of carbon-flux distribution through the central metabolic pathways.
Growth on glucose has been previously shown to involve a high flux (> 50% of
total glucose consumption) via the pentose pathway to generate anabolic reducing
equivalents. NMR analysis of carbon-isotope distribution patterns of the
glutamate pool after growth on 1-13C- or 6-13C-enriched fructose indicates that
the contribution of the pentose pathway is significantly diminished during
exponential growth on fructose with glycolysis being the predominant pathway (80%
of total fructose consumption). The increased flux through glycolysis during
growth on fructose is associated with an increased NADH/NAD+ ratio susceptible to
inhibit both glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenase,
and provoking the overflow of metabolites derived from the substrates of these
two enzymes. The biomass yield observed experimentally is higher than can be
estimated from the apparent quantity of NADPH associated with the pentose pathway
and the flux through isocitrate dehydrogenase, suggesting an additional reaction
yielding NADPH. This may involve a modified tricarboxylic acid cycle involving
malic enzyme, expressed to significantly higher levels during growth on fructose
than on glucose, and a pyruvate carboxylating anaplerotic enzyme.
PMID- 9652401
TI - Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6
bisphosphatase heart isoform gene (PFKFB2).
AB - 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) is a
bifunctional enzyme that catalyzes the synthesis and degradation of Fru-2,6-P2, a
key regulator of glycolysis. In mammals, several genes have been found to code
for different PFK-2/FBPase-2 isoforms that differ in tissue distribution and
enzymatic activities. In the present study, we report the characterization of the
PFK-2/FBPase-2 heart isoform gene in humans (PFKFB2), including a full analysis
of repetitive sequences and potential transcription binding sites. The genomic
sequence of the PFKFB2 gene spans 22,485 bp and contains 15 exons. Heart cDNA
analysis shows that PFKFB2 codes for a protein of 505 amino acids with a deduced
molecular mass of 58,849 Da. Comparison of the human PFKFB2 gene to the
homologous genes in rat and ox outlines a significant conservation of the intron
exon structure, sequence of 5' and 3' flanking regions, and simple sequence
repetitive element positions. Most important, the human heart PFK-2/ FBPase-2
protein was found to retain all the important regulatory sites, as well as the
catalytic and substrate binding sites identified in the rat and bovine heart
isoforms, suggesting that the human enzyme is regulated in a manner similar to
that observed in these organisms.
PMID- 9652402
TI - Evidence of an overlap between the two half-sites of UAS1-B/CYC1--a new model for
Cyp1p (Hap1p) DNA binding.
AB - Cyp1p (Hap1p) is a yeast transcriptional regulator belonging to the zinc-cluster
family. CGGNNNTANCGG was identified by PCR selection as the DNA sequence allowing
its optimal binding. Nevertheless, this sequence is not a consensus sequence, the
simultaneous presence of the two CGGs and the TA generally not being found in the
known natural Cyp1p targets. In fact, our previous studies showed that the
mechanism of Cyp1p DNA binding was target dependent. Data concerning the binding
of Cyp1p to the UAS1-B/CYC1 are presented here. This target, containing the
CGGGGTTTACGG sequence, was found to present the particular ability of stabilizing
the binding of only one molecule of some monomeric Cyp1p fragments. This property
was used to investigate the actual contribution of the TT and CGG sequences in
the binding of Cyp1p. Our results indicate that each CGG belongs to a different
half-site and, in contrast to a previous hypothesis, that the T nucleotide
located four bases downstream from the left CGG is essential for the binding of
one monomer to each half-site. The two half-sites of the UAS1-B/CYC1 thus
overlap.
PMID- 9652403
TI - Molecular cloning, gene structure and expression profile of mouse C1 inhibitor.
AB - The gene encoding C1 inhibitor, the major control element of activation of the
classical pathway of complement and a major inhibitor of several plasma serine
proteases, has been studied only in man, where deficiency of C1 inhibitor results
in the dominantly transmitted disease hereditary angioedema. Full-length mouse C1
inhibitor cDNA and genomic clones were isolated and characterized as a first step
towards the complete characterization of the pattern of C1 inhibitor expression
and the production of an animal model of C1 inhibitor deficiency. Restriction
enzyme and sequence analyses of a full-length genomic clone demonstrated that the
mouse gene has the same structure as the human homologue, but differs in size (9
kb versus 17 kb), mostly due to the presence of repetitive Alu elements in the
human gene. Sequence comparisons in the promoter region indicate important
similarities, i.e. the absence of a TATA box, the presence of an initiator
sequence encompassing the transcription-start site and of a gamma-interferon
activated sequence (GAS) element at position -124 of the human sequence. A
stretch of about 100 nucleotides in intron 1 reveals an unusually high degree of
conservation for non-coding sequences and contains non-canonical but conserved
tandemly arranged GAS elements at positions 369 and 388 of the human sequence.
This finding supports the conclusions of functional studies on the human C1INH
gene indicating a role of this region in modulation of transcription by
interferons. The profile of C1 inhibitor expression in mouse liver, lung, heart,
kidney, spleen and brain was determined by quantitative northern blot analysis.
PMID- 9652404
TI - Primary structure and high expression of human agrin in basement membranes of
adult lung and kidney.
AB - Agrin is a heparan sulfate proteoglycan involved in the development of the
neuromuscular junction during embryogenesis. In addition to this well
characterized function, agrin may have additional functions in other tissues and
during other stages in development. In this study we present the cDNA sequence of
human agrin, and demonstrate a high agrin content in adult basement membranes.
The N-terminal domain of human agrin is highly similar to that of chick agrin,
suggesting a similar function in laminin binding. The presence of three SGXG
sequences supports serine-linked glycosylation of the core protein, two sites
being particularly favorable for heparan sulfate attachment. Comparison of levels
of agrin mRNA in fetal and adult human tissues showed a remarkable upregulation
in adult kidney and lung. In both tissues truncated agrin transcripts were
detected, lacking the region that encodes the laminin-binding domain. The high
transcription levels in lung and kidney corresponded with the accumulation of
agrin in the alveolar and glomerular basement membranes, suggesting a filtration
associated function. These data provide new directions for investigating the role
of agrin in its different physiological environments, including the basement
membranes of the neuromuscular junction, kidney and lung.
PMID- 9652405
TI - Oligonucleotide facilitators enable a hammerhead ribozyme to cleave long RNA
substrates with multiple-turnover activity.
AB - Trans-acting hammerhead ribozymes are usually efficient in cleaving short RNA
model substrates under both single-turnover and multiple-turnover conditions. In
contrast, when long RNAs are the substrates, the cleavage efficiency of these
ribozymes decreases, including a loss of multiple-turnover activity in many
cases. Since target substrates for potential therapeutical purposes are mostly
long RNAs, a multiple-turnover cleavage of long RNAs would essentially increase
the efficiency of hammerhead ribozymes. Therefore, we explored if oligonucleotide
facilitators, capable of enhancing multiple-turnover activity with short
substrates, can also affect or cause multiple turnover with long substrates. We
examined the effects of 12-base and 24-base oligonucleotide facilitators on the
multiple-turnover activity with substrates of different length containing 39-,
452- and 942-base sequences of the human tissue factor (HTF) mRNA. In the absence
of facilitator, the ribozyme cleaved only the 39-base substrate with multiple
turnover activity, but not the long 452-base and 942-base substrates. However,
facilitator addition enabled the ribozyme to cleave even the 452-base and the 942
base substrates with multiple-turnover activity. All facilitators tested showed a
remarkable activating effect with the long substrates. The data demonstrate that
a hammerhead ribozyme which, by itself, can only act as a single-turnover
catalyst with long substrates, can be switched by facilitators into a multiple
turnover catalyst. Thus, the inactivation of long target RNAs in multiple
turnover reactions may be achieved by addition of oligonucleotide facilitators.
PMID- 9652406
TI - Different derivations of knowledge-based potentials and analysis of their
robustness and context-dependent predictive power.
AB - The possibility of defining effective potentials from known protein structures,
which are sufficiently accurate to be used for protein-structure-prediction
purposes, is investigated. Three types of distance potentials and three types of
backbone torsion potentials are defined, based on propensities of amino acid
pairs to be separated by a given spatial distance or to be associated to a
backbone torsion angle domain. Their differences reside in the way the physical
correlations between the amino acids and the conformational states are extracted
from the bulk interactions due to the presence of many residues in a protein. For
the distance potentials, a physical meaning can be associated to the different
definitions, given that some of the potentials favor hydrophobic interactions and
others favor interactions between oppositely charged residues. The performance of
the different torsion and distance potentials in structure prediction procedures,
in particular native-fold recognition and evaluation of protein stability changes
upon point mutations, is analyzed. It appears to differ according to the specific
proteins and protein environments. In particular, one of the distance potentials
performs better than the others for membrane proteins and in protein regions
involving charged residues, but less well in other protein regions. Furthermore,
the dependence of the potentials on the characteristics of the proteins from
which they are derived is analyzed. It is shown that the dependence of the
potentials on the length, amino acid composition and secondary-structure content
of the proteins from the dataset is either very limited or rather strong,
according to the type of potential. The results obtained suggest that the main
problem limiting the performance of database-derived potentials is their lack of
universality: each potential describes with satisfactory accuracy only the
interactions present in certain protein environments.
PMID- 9652407
TI - Transferrins--a mechanism for iron uptake by lactoferrin.
AB - Iron uptake by bovine lactoferrin from nitrilotriacetatoFe(III) [FeN(Ac)3] in the
presence of bicarbonate has been investigated at pH 7.1-8.7. Deprotonated
apolactoferrin interacting with bicarbonate or carbonate extracts iron from
nitrilotriacetatoFe(III); the direct second-order rate constant k1 = (4.90 +/-
0.20)x10(4) M(-1) s(-1), a reverse second-order rate constant k(-1) = (1.80+/
0.05)x10(5) M(-1) s(-1), and the iron-exchange equilibrium constant K1 = 0.25+/
0.05. The newly formed iron-protein complex loses a single proton with proton
dissociation constant K3a = (17+/-0.5) nM, then undergoes a modification in its
conformation followed by the loss of two or three protons; the first-order rate
constant k2 = (1.0+/-0.10) s(-1). This induces a new modification in the
conformation; the first-order rate constant k3 = (8.75+/-0.40)x10(-3) s(-1). This
second modification in conformation controls the rate of iron uptake by the N
site of the protein and is followed by a single proton loss; K5a = 8.0 nM.
Finally, the holoprotein or the monoferric lactoferrin in their final
equilibrated states are produced by a third modification in the conformation
occurring in about 9000 s. The mechanism of iron uptake by lactoferrin is very
similar to that of serum transferrin with a cooperativity between the C and N
sites upon iron uptake but with lower rates, higher affinities and at least one
more proton loss involved. These differences may be the result of slight
discrepancies in the intimate structures of binding sites for serum transferrin
and lactoferrin. In order to analyse the cooperativity between these iron-binding
sites, the three-dimensional position of the chain of amino acid residues
separating the N and C lobes of human apo-, holo- and dicopper-lactoferrin have
been compared by the recognition of the three-dimensional shape dissimilarity
program. The interlobe peptides of human hololactoferrin and apolactoferrin
showed only 75.5 % tridimensional similarity, indicating that iron uptake affects
the three-dimensional structure of the interlobe chain.
PMID- 9652408
TI - Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the
biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L
aspartate (cyanophycin).
AB - Cyanophycin (multi-L-arginyl-poly-L-aspartate), a water-insoluble reserve polymer
of cyanobacteria, is a product of nonribosomal peptide synthesis. The
purification of cyanophycin synthetase of the cyanobacterium Anabaena variabilis
is described. In sodium dodecylsulfate/polyacrylamide gel electrophoresis, the
enzyme preparation shows one band with an apparent molecular mass of 100 kDa. The
native enzyme has an apparent molecular mass of approximately 230 kDa, as
determined by size-exclusion chromatography, suggesting that the active form is a
homodimer. During catalysis, ATP is converted to ADP. The gene coding for
cyanophycin synthetase has been identified in the sequenced genome of
Synechocystis sp. PCC 6803. The C-terminal 60% of the deduced amino acid sequence
of cyanophycin synthetase show sequence similarity to enzymes of the superfamily
of ligases involved in the biosynthesis of murein and of folyl-poly(gamma
glutamate). Cells of Escherichia coli harbouring the gene on a plasmid express
active synthetase and accumulate cyanophycin-like material. The results prove
that a single enzyme catalyzes the de novo synthesis of cyanophycin.
PMID- 9652409
TI - Purification, characterization and cloning of an aspartic proteinase inhibitor
from squash phloem exudate.
AB - Phloem exudate from squash fruit contains heat-inactivated material which
inhibits pepsin activity. This inhibitory activity was purified by mild acid
treatment, chromatography on trypsin-agarose, Sephadex G-75 and reverse-phase
HPLC, resulting in the elution of three peaks with pepsin-inhibitory activity. N
terminal sequencing indicated a common sequence of MGPGPAIGEVIG and the presence
of minor species with seven- or two-amino-acid N-terminal extensions beyond this
point. Microheterogeneity in this end sequence was exhibited within and between
two preparations. Internal sequencing of a major peak after a trypsin digestion
gave the sequence FYNVVVLEK. The common N-terminal sequence was used to design a
degenerate primer for 3' rapid amplification of cDNA ends and cDNA clones
encoding two isoforms of the inhibitor were obtained. The open reading frames of
both cDNAs encoded proteins (96% identical) which contained the experimentally
determined internal sequence. The amino acid content calculated from the
predicted amino acid sequence was very similar to that measured by amino acid
analysis of the purified inhibitor. The two predicted amino acid sequences (96
residues) had neither similarity to any other aspartic proteinase inhibitor nor
similarity to any other protein. The inhibitors have a molecular mass of 10,552
Da, measured by matrix-assisted laser-desorption ionisation time-of-flight mass
spectrometry and approximately 10,000 Da by SDS/PAGE, and behave as dimers of
approximately 21,000 Da during chromatography on Superdex G-75 gel-filtration
medium. The calculated molecular masses from the predicted amino acid sequences
were 10,551 Da and 10,527 Da. The inhibitor was capable of inhibiting pepsin (Ki
= 2 nM) and a secreted aspartic proteinase from the fungus Glomerella cingulata
(Ki = 20 nM). The inhibitor, which is stable over acid and neutral pH, has been
named squash aspartic proteinase inhibitor (SQAPI).
PMID- 9652410
TI - Structural determination of the O-antigenic polysaccharide from Escherichia coli
O141.
AB - The structure of the O-antigenic polysaccharide from Escherichia coli O141 has
been determined. NMR spectroscopy and sugar and methylation analyses were the
principal methods used. The sequence of the sugar residues could be determined by
NOESY and heteronuclear multiple-bond connectivity (HMBC-) NMR experiments. The
polysaccharide is composed of pentasaccharide repeating units with 1 O-acetyl
group/repeating unit. The following structure, where Rha is 6-deoxymannose is
concluded: carbohydrate sequence [see text].
PMID- 9652411
TI - Dextran strongly increases the Michaelis constants of oxidative phosphorylation
and of mitochondrial creatine kinase in heart mitochondria.
AB - Macromolecules restore the morphological changes which occur upon isolation of
mitochondria in normally used isolation media. It was shown that in the presence
of dextrans the permeability of mitochondrial outer membrane for adenine
nucleotides decreases which may have considerable implications for the transport
of ADP into the mitochondria. In this study the effect of dextran on the apparent
Michaelis constants of oxidative phosphorylation and mitochondrial creatine
kinase (mi-CK) of rat heart mitochondria was investigated. Mitochondria were
isolated either in normally used isolation media or in the additional presence of
15% dextran 20 in order to avoid changes in the oncotic conditions on the
mitochondria during preparation and investigation. Except for an increased
contamination with extramitochondrial ATPases the basic functional properties of
these mitochondria were normal. With oxygraphic measurements it was found that
Km(ADP) of oxidative phosphorylation increased from 16 +/- 4 microM ADP (without
dextran) to 50 +/- 15 microM (15% dextran 20) and to 122 +/- 62 microM (25%
dextran 20) irrespective of the mode of preparation of the mitochondria. Using
spectrophotometric measurements the effect of dextran on the Km(ATP) of mi-CK was
investigated in three systems (a) as soluble enzyme, (b) bound to mitoplasts, (c)
and in intact rat heart mitochondria. The addition of 10% dextran had no effect
on kinetic properties of solubilized mi-CK. In intact heart mitochondria,
however, the addition of dextran caused an augmentation of Km(ATP) from 332 +/-
91 microM (control) to 525 +/- 150 microM ATP (10% dextran) and 641 +/- 160
microM ATP (30% dextran). In mitoplasts the effect of dextran disappeared
(control, 230 +/- 19 microM ATP; 10% dextran, 238 +/- 28 microM ATP) indicating
that the outer mitochondrial membrane is a prerequisite for the modulation of the
transport of adenine nucleotides into the intermembrane space by macromolecules.
To investigate the effects of viscosity of dextran solutions on the diffusion of
adenine nucleotides across the outer membrane, dextrans with different molecular
size (20, 40 70 and 500 kDa) were used. The viscosity of the 10% solutions
drastically increased with the molecular size of the dextrans used, but the
effects of different dextran solutions on the kinetic constants were the same.
From these results it was concluded that neither the viscosity nor the molar
concentration but the content of macromolecules (mass/vol.) correlates with
restrictions of diffusion into the intermembrane space of mitochondria with
intact outer membranes. Assuming that a dextran concentration of 15% mimicks the
intracellular oncotic pressure on mitochondria in vivo, the apparent Km(ATP) of
oxidative phosphorylation within the intact cell seems to be about 50 microM ADP
which is somewhat higher than the cytoplasmic free ADP concentration as reported
for the intact heart.
PMID- 9652412
TI - Transport of LDS-751 from the cytoplasmic leaflet of the plasma membrane by the
rhodamine-123-selective site of P-glycoprotein.
AB - P-glycoprotein is an ATP-dependent transporter of an extremely wide variety of
lipophilic compounds. We showed previously [Shapiro, A. B. & Ling, V. (1997a)
Eur. J. Biochem. 250, 130-137] that P-glycoprotein contains two drug transporting
sites, dubbed H (for Hoechst 33342-selective) and R (for rhodamine-123
selective), that interact with positive cooperativity. The H site transports 2-[2
(4-ethoxyphenyl)-6-benzimidazolyl]-6-(1-methyl-4-piperazyl)be nzimidazole
(Hoechst 33342) from the cytoplasmic leaflet of the plasma membrane to the
aqueous extracellular medium [Shapiro, A. B. & Ling, V. (1997b) Eur. J. Biochem.
250, 122-129]. The environment from which the R site transports its substrates is
unknown. In this paper, we used the fluorescent DNA dye 2-[4-[4
(dimethylamino)phenyl]-1,3-butadienyl]-3-ethylbenzothiazolium perchlorate (LDS
751), a substrate of the R site, to address this issue. LDS-751 which, like
Hoechst 33342, exhibits lipid-dependent fluorescence and slow transleaflet
diffusion, allowed us to use the same methodology that we used for the H site to
study the location of the R site. As with Hoechst 33342, the specific initial
rate of LDS-751 transport by P-glycoprotein-rich, isolated plasma membrane
vesicles from CH(R)B30 cells was directly proportional to the amount of membrane
bound LDS-751 and inversely proportional to the concentration of free, aqueous
LDS-751. This result demonstrates that the R site of P-glycoprotein transports
LDS-751 out of the lipid membrane. The slight decrease, instead of an increase,
in the initial rate of active transport of LDS-751 with the amount of time
elapsed for slow diffusion of LDS-751 from the cytoplasmic leaflet to the
extracellular leaflet indicates that the R site of P-glycoprotein removes LDS-751
from the cytoplasmic leaflet of the plasma membrane. Thus, both known drug
transporting sites of P-glycoprotein remove their substrates from the cytoplasmic
leaflet. Since all of the P-glycoprotein substrates we have examined so far are
recognized by one or both of the two known drug-transporting sites, these two
sites in the cytoplasmic leaflet of the plasma membrane may be able to account
for all substrate transport by P-glycoprotein.
PMID- 9652413
TI - Stoichiometry of coupling of rhodamine 123 transport to ATP hydrolysis by P
glycoprotein.
AB - In order to describe the transport mechanism of P-glycoprotein, it is essential
to know the coupling ratio, i.e. the moles substrate transported/mole ATP
hydrolyzed. P-glycoprotein couples ATP hydrolysis at two ATP-binding sites to
transport of a wide variety of neutral or cationic lipophilic compounds.
Previously published coupling ratios have fallen within the range 0.02-0.8 mol
substrate transported/mol ATP hydrolyzed. We studied the energetics of transport
by P-glycoprotein, performing quantitative measurements of the rates of ATP
hydrolysis and transport of rhodamine 123 by P-glycoprotein, using isolated P
glycoprotein-rich plasma membrane vesicles. The continuous fluorescence-based
assay of rhodamine 123 transport allowed accurate measurement of initial
transport rates. Since we measured uptake of rhodamine 123 into the vesicles as a
loss of fluorescence, we avoided the problem of high background due to substrate
binding to the membranes. The coupling ratio of the transport reaction increased
as the rhodamine 123 concentration increased, showing that the basal ATPase
activity of P-glycoprotein was progressively recruited for rhodamine 123
transport. Both of the previously identified transport sites of P-glycoprotein
[Shapiro, A. B. & Ling, V. (1997a) Eur J. Biochem. 250, 130-137] were involved in
transport of saturating concentrations of rhodamine 123. At saturating rhodamine
123 and 0.3 mM ATP, the coupling ratio was 0.83, suggesting a mechanistic
coupling ratio of 1. Interestingly, the coupling ratio decreased as the ATP
concentration increased so that, at 1.5 mM, close to the cytoplasmic
concentration of ATP, the coupling ratio was 0.57. The physiological significance
of this effect is not yet understood.
PMID- 9652415
TI - Role of the actin cytoskeleton in regulating the outer phosphatidylethanolamine
levels in yeast plasma membrane.
AB - Transbilayer phosphatidylethanolamine (PtdEtn) movements in the plasma membrane
of Saccharomyces cerevisiae are regulated by an ATP-dependent, protein-mediated
process(es). To examine whether this process is influenced by the actin
cytoskeleton, we have studied the PtdEtn translocation in S. cerevisiae cells
after treatment with microfilament disrupting and microtubule-disrupting agents.
PtdEtn translocation was studied by measuring the external PtdEtn levels, using
fluorescamine as the external membrane probe, in the ATP-depleted, ATP-depleted
and repleted, and N-ethylmaleimide-treated cells. The microfilaments and
microtubules were disrupted by treatment with various cytochalasins and
colchicine (or benomyl) respectively PtdEtn translocation became abnormal in the
cytochalasin-treated cells but not in cells that were treated with microtubule
disrupting agents, such as colchicine or benomyl. These results have been
interpreted to suggest that the actin cytoskeleton is involved in regulating the
PtdEtn translocase activity in the yeast cell plasma membrane.
PMID- 9652414
TI - Control of oxidative phosphorylation, gluconeogenesis, ureagenesis and ATP
turnover in isolated perfused rat liver analyzed by top-down metabolic control
analysis.
AB - We have analyzed the control exerted by the pathways of oxidative
phosphorylation, gluconeogenesis, ureagenesis, and maintenance ATP consumption
over each other's rates in isolated, perfused rat liver using top-down metabolic
control analysis. The livers from fasted rats were perfused with 3
hydroxybutyrate as respiratory substrate, lactate as substrate for
gluconeogenesis, and ammonium as substrate for urea synthesis, in conditions
where these pathways were only linked by their common intermediates: ATP, ADP,
and Pi. The rates of oxygen consumption, glucose and urea synthesis were measured
continuously. The pathways were perturbed either by adding specific inhibitors or
by adding new pathways that consumed ATP, and the relative changes in pathway
rates were used to calculate the flux control coefficients of each pathway over
all pathway rates. When the liver was in a relatively inactive metabolic state,
where ATP was only being used by the maintenance ATP-consuming pathways, then
essentially all the control over ATP production and consumption was located in
the maintenance ATP consumers with ATP production having no control. Whereas,
when the liver was in a highly active state using extra ATP for both glucose and
urea synthesis, then ATP production (from oxidative phosphorylation) had strong
control over its own rate and the rates of glucose and urea synthesis, but
gluconeogenesis and ureagenesis still had strong control over their own rates and
negative control over each others rates, i.e. they competed for the limited ATP
supply. The rate of the maintenance ATP consumers is remarkably insensitive to
changes in ATP production and consumption, but exerts considerable control over
all other pathways. These results indicate that the general assumption that the
rates of ATP production and consumption are controlled exclusively by ATP
consumers is false under conditions where a significant amount of ATP is used for
biosynthetic processes, such as glucose and urea synthesis, and indicate that the
latter processes may be partly controlled by regulators of ATP production and by
other ATP-consuming pathways.
PMID- 9652416
TI - Cervical antibody responses to a herpes simplex virus type 2 glycoprotein subunit
vaccine.
AB - Effective vaccines against genital herpes simplex virus type 2 (HSV-2) may need
to induce genital tract immune responses. To determine local antibody responses
to HSV-2 glycoproteins gB2 and gD2 in an intramuscular subunit vaccine, cervical
secretions from HSV-seronegative women and HSV-1-seropositive women were tested
for IgG and IgA to gB2 and gD2 by enhanced chemiluminescence Western blot. Most
(94%) of the seronegative subjects developed cervical IgG to gB2, IgG to gD2, and
IgA to gB2; 72% developed IgA to gD2. All HSV-1-seropositive subjects had
cervical IgG responses to vaccine gB2 and gD2, 85% had IgA responses to gB2, and
50% had IgA responses to gD2. Responses were more rapid and titers more
consistently sustained in the HSV-1-seropositive women. Further, vaccination
resulted in cervical IgG and IgA titers comparable to those to HSV-2 gB2 and gD2
in response to recurrent HSV-2 genital infection.
PMID- 9652417
TI - Limited variability of glycoprotein gene sequences and neutralizing targets in
herpes simplex virus type 2 isolates and stability on passage in cell culture.
AB - Nucleotide sequence analyses of polymerase chain reaction-amplified genes were
performed to determine whether adaptation of herpes simplex virus type 2 to
replication in cultured cells or in internal organs during neonatal disseminated
disease results in selection of variants with altered forms of three
glycoproteins (gB, gC, or gD) that influence virus entry into cells. No
variations in sequence were noted as a consequence of in vitro passage or
replication in different organs. Five viruses from different subjects differed
with respect to gB, gC, and gD gene sequences, expressing four distinct forms of
gB, three of gC, and two of gD. These differences did not confer resistance to
neutralization by guinea pig or human antisera from subjects immunized with
recombinant gB or gD vaccines and may not be consequential for vaccine
development.
PMID- 9652418
TI - Granulocyte-macrophage colony-stimulating factor expressed in T cells mediates
immunity against herpes simplex virus type 1 encephalitis.
AB - A model of herpes simplex virus type 1 (HSV-1) infection was developed in rats to
study systemic immune responses elicited by intravitreous inoculation of the
virus. HSV-1 inoculation led to distinct granulocyte-macrophage colony
stimulating factor (GM-CSF)-producing memory T cells, which did not develop in
rats inoculated with either HSV-1 intraperitoneally or inactivated HSV-1
intravitreously. On subsequent intraperitoneal viral boosting, systemic GM-CSF
production was elicited as a secondary immune response that caused
neutroeosinophilia. To examine the role of GM-CSF in anti-herpetic immunity,
cytokine-producing and -nonproducing rats were intravitreously challenged with
HSV-1, which causes lethal encephalitis. Only intravitreously primed rats were
protected upon production of GM-CSF. Furthermore, pretreatment with recombinant
GM-CSF protected unimmunized rats against the encephalitis. It is thus strongly
suggested that the production of GM-CSF leads to anti-HSV-1 immunity against the
transneuronal spread of challenged HSV-1 within the visual system.
PMID- 9652420
TI - Identification of the Oka strain of the live attenuated varicella vaccine from
other clinical isolates by molecular epidemiologic analysis.
AB - A method was developed to distinguish the Oka vaccine strain of varicella-zoster
virus (VZV) from other clinical isolates. The molecular characteristics of 52
clinical isolates from varicella or zoster patients with no history of VZV
vaccination and the Oka strain, including vaccine and parental viruses, were
analyzed by PstI cleavage of the PstI site-less (PSL) region. This was followed
by single-strand conformational polymorphism (SSCP) after polymerase chain
reaction amplification of repeating region 2 (R2). Most of the clinical isolates
tested, especially recent isolates, had a PstI site in the PSL region, but the
Oka strain did not. The SSCP patterns of R2 in Oka strain virus differed from
those of other viruses. These results suggest that analysis of the PstI site
followed by SSCP of R2 will be useful for identifying the Oka vaccine virus in
isolates.
PMID- 9652419
TI - T cells specific for the triggering virus infiltrate the eye in patients with
herpes simplex virus-mediated acute retinal necrosis.
AB - Acute retinal necrosis (ARN) is a rare, potentially blinding retinal disease
resulting from ocular infections with herpes simplex virus (HSV) or varicella
zoster virus (VZV). To determine the antigen specificity and functional
characteristics of ocular infiltrating T cells in ARN, T cells were isolated and
expanded nonspecifically from intraocular fluid (IOF) samples from 2 patients
with HSV-1- and 3 with VZV-mediated ARN. HSV-specific T cell reactivity could be
detected only in the IOF-derived T cell lines (TCLs) of the 2 patients with HSV
mediated ARN. These TCLs consisted of both HSV type-common and type-specific CD4+
and CD8+ T cell clones (TCCs) with differential T cell receptor usage.
Irrespective of their phenotype, the TCCs were cytolytic and secreted interferon
gamma, tumor necrosis factor-alpha, interleukin-4, and interleukin-5. In both
patients, the antigen specificity of a substantial number of HSV-1-specific TCCs
could be mapped to approximately 0.67-0.73 HSV-1 map units. The data presented
suggest the contribution of T cells, specific for the triggering virus, to the
pathogenesis of ARN.
PMID- 9652421
TI - Association between MHC class II alleles and clearance of circulating hepatitis C
virus. Members of the Trent Hepatitis C Virus Study Group.
AB - The frequencies of HLA class I antigens and class II haplotypes were compared in
subjects with previous (polymerase chain reaction [PCR]-negative) or with
persistent (PCR-positive) hepatitis C virus (HCV) infection and in HCV patients
with mild versus severe histologic activity scores on liver biopsy. The DRB1*11
allele group was found in 11 (31.4%) of 35 subjects with previous infection and
in 11 (8.2%) of 135 subjects with persistent infection (P < .001). The DQB1*0301
allele was found in 18 (51.4%) of 35 subjects with previous infection and in 33
(24.4%) of 135 patients with persistent infection (P < .002). Both observations
remained significant after correction for multiple testing. No significant
association was shown between severity of disease and any HLA class I or II type.
Thus, the HLA class II alleles DRB1*11 and DQB1*0301 are associated with
clearance of circulating HCV.
PMID- 9652422
TI - Human papillomavirus, anal squamous intraepithelial lesions, and human
immunodeficiency virus in a cohort of gay men.
AB - Cross-sectional associations between human papillomavirus (HPV), anal squamous
intraepithelial lesions (SIL), and human immunodeficiency virus (HIV) were
studied in a cohort of gay men. HPV DNA was detected by generic and type-specific
polymerase chain reaction (PCR) probes and hybrid capture assay (HC). HPV virus
load was estimated by HC relative light unit (RLU) ratio. HPV prevalence, number
of HPV types detected, and HC RLU ratios were each greater in HIV-positive than
HIV-negative participants. Further, among HIV-positive men, HC RLU ratio was
inversely associated with CD4 cell count. SIL was more frequent in HIV-positive
participants, particularly those with a CD4 cell count <200/microL and was
positively associated with HPV. Men with a high HC RLU ratio were nearly 3 times
more likely to have SIL than were those both PCR- and HC-negative. These data
support that HIV augments HPV-associated anal disease in this population.
PMID- 9652423
TI - Pandemic versus epidemic influenza mortality: a pattern of changing age
distribution.
AB - Almost all deaths related to current influenza epidemics occur among the elderly.
However, mortality was greatest among the young during the 1918-1919 pandemic.
This study compared the age distribution of influenza-related deaths in the
United States during this century's three influenza A pandemics with that of the
following epidemics. Half of influenza-related deaths during the 1968-1969
influenza A (H3N2) pandemic and large proportions of influenza-related deaths
during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1)
pandemics occurred among persons <65 years old. However, this group accounted for
decrementally smaller proportions of deaths during the first decade following
each pandemic. A model suggested that this mortality pattern may be explained by
selective acquisition of protection against fatal illness among younger persons.
The large proportion of influenza-related deaths during each pandemic and the
following decade among persons <65 years old should be considered in planning for
pandemics.
PMID- 9652424
TI - Evolution of cytotoxic T lymphocyte responses to human immunodeficiency virus
type 1 in patients with symptomatic primary infection receiving antiretroviral
triple therapy.
AB - The impact of highly active antiretroviral treatment (HAART) on anti-human
immunodeficiency virus (HIV) cytotoxic T lymphocytes (CTL) was studied in 17
patients with recent symptomatic HIV-1 primary infection receiving triple
combination therapy. Anti-HIV CTL were initially detected in 15 patients. In 6,
CTL disappeared rapidly and persistently after initiation of therapy. Most of
them had a rapid and sustained decrease in plasma HIV RNA to undetectable levels.
Conversely, in 6 other patients, CTL remained detectable, which was associated
with a less efficient control of viral replication. In 3 others, CTL disappeared
only transiently, without clear correlation with the virologic profile.
Altogether, despite individual variations, there was a positive correlation
between viral replication and anti-HIV-1 cytotoxicity in most subjects,
suggesting that the persistence of viral antigens is the main determinant for the
maintenance of CTL activity. This raises the question of the potential benefit of
anti-HIV CTL induction by immunotherapy in acute seroconverters treated by HAART.
PMID- 9652425
TI - Immunologic responses associated with 12 weeks of combination antiretroviral
therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS
Clinical Trials Group Protocol 315.
AB - Human immunodeficiency virus (HIV)-1 infection is associated with progressive
cell-mediated immune deficiency and abnormal immune activation. Although highly
active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte
counts and decrease the risk of opportunistic complications, the effects of these
treatments on immune reconstitution are not well understood. In 44 persons with
moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine,
lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P <
.0001). Circulating numbers of naive and memory CD4 T lymphocytes (P < .001),
naive CD8 T lymphocytes (P < .004), and B lymphocytes (P < .001) increased.
Improved lymphocyte proliferation to certain antigens and a tendency to
improvement in delayed-type hypersensitivity also were seen. Dysregulated immune
activation was partially corrected by this regimen; however, the perturbed
expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte
populations was not significantly affected. Ongoing studies will ascertain if
longer durations of virus suppression will permit more complete immune
restoration.
PMID- 9652426
TI - Zidovudine treatment in patients with primary (acute) human immunodeficiency
virus type 1 infection: a randomized, double-blind, placebo-controlled trial.
DATRI 002 Study Group. Division of AIDS Treatment Research Initiative.
AB - A multicenter, double-blind, placebo-controlled trial randomized 28 patients with
primary (acute) human immunodeficiency virus (HIV)-1 infection (PHI) to receive
zidovudine, 1000 mg daily, or placebo for 24 weeks. At week 48, compared with
placebo patients, zidovudine-treated patients had significantly higher CD4 cell
counts (zidovudine, 666 cells/mm3; placebo, 362; P = .004) and lower peripheral
blood mononuclear cell (PBMC) culture titers (zidovudine, 0.58 log infectious
units per million cells; placebo, 1.68; P = .02) but no difference in plasma RNA
(zidovudine, 3.93 log copies/mL; placebo, 4.00; P = .83). Serious adverse events
and minor clinical events were infrequent and comparable in both arms. There were
two deaths: 1 patient died of sepsis and renal disease (zidovudine arm), and 1
patient died of sepsis and tension pneumothorax (placebo arm). Six months of high
dose zidovudine initiated during PHI results in higher CD4 cell counts and lower
PBMC culture titers but no difference in plasma HIV-1 RNA. Further studies with
more potent antiretroviral combination therapies are warranted.
PMID- 9652427
TI - First human trial of a DNA-based vaccine for treatment of human immunodeficiency
virus type 1 infection: safety and host response.
AB - A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env
and rev genes was tested for safety and host immune response in 15 asymptomatic
HIV-infected patients who were not using antiviral drugs and who had CD4+
lymphocyte counts of > or = 500 per microliter of blood. Successive groups
received three doses of vaccine (30, 100, or 300 microg) at 10-week intervals in
a dose-escalation trial. Vaccine administration induced no local or systemic
reactions, and no laboratory abnormalities were detected. Specifically, no
patient developed anti-DNA antibody or muscle enzyme elevations. No consistent
change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration.
Antibody against gp120 increased in individual patients in the 100- and 300
/microg groups. Some increases were noted in cytotoxic T lymphocyte activity
against gp160-bearing targets and in lymphocyte proliferative activity. The
safety and potential immunogenicity of an HIV-directed DNA-based vaccine was
demonstrated, a finding that should encourage further studies.
PMID- 9652428
TI - Association of human immunodeficiency virus (HIV) load early in life with disease
progression among HIV-infected infants. New York City Perinatal HIV Transmission
Collaborative Study Group.
AB - The utility of RNA virus load to predict progression of human immunodeficiency
virus (HIV)-1 disease was assessed in 89 HIV-1-infected children. Of 22 virus
load values during week 1 of life, 17 were below the detection threshold.
Geometric mean virus load increased to approximately 7 x 10(5) copies/mL by week
4, was sustained throughout the first 6 months of life, and then declined to 1.6
x 10(5) copies/mL during the third year. Samples from week 1 of life had little
predictive value, but virus load during days 7-30 strongly predicted progression
to CDC-3 classification or death (P = .024; risk ratio = 1.6), and virus load
during months 2-3 predicted progression to CDC-C or death within the first 6
months of life (P = .002, risk ratio = 11). Virus load was highly associated with
imminent vulnerability to CDC-C or death (P = .002) during the first 18 months of
life. Except for values from the first week of life, virus load at any age
through 18 months is strongly associated with risk of HIV disease progression.
PMID- 9652429
TI - Mortality in the first 2 years among infants born to human immunodeficiency virus
infected women in Harare, Zimbabwe.
AB - Transmission of human immunodeficiency virus (HIV) and mortality was studied
among infants of infected women in Zimbabwe. Of 367 infants born to HIV-infected
women, 72 (19.6%) died compared with 20 (5.4%) of 372 infants of uninfected women
(P < .01). Infection by HIV DNA polymerase chain reaction among infants who
survived >7 days and died within 2 years could be assessed in 87% (58/67) of
infants of infected women and 83% (5/6) of infants of uninfected women;
transmission occurred in 40 of 58 infants. Among 27 infected infants tested at
birth, 19 (70%), 5 (19%), and 3 (11%) were apparently infected via in utero,
intrapartum or early postpartum, and late postpartum transmission, respectively.
The majority of HIV-infected infants who died in the first 2 years of life were
likely to have acquired in utero infection.
PMID- 9652430
TI - Trends in AIDS-related opportunistic infections among men who have sex with men
and among injecting drug users, 1991-1996.
AB - Incidence trends for the 13 most frequent AIDS-defining opportunistic infections
(OIs) among men who have sex with men (MSM, n = 15,588) and injecting drug users
(IDUs, n = 4475) were examined using data abstracted from medical records in >90
hospitals and clinics in nine US cities during 1991-1996. Among MSM, the most
frequent OIs were Mycobacterium avium complex (MAC) disease, Pneumocystis carinii
pneumonia (PCP), and cytomegalovirus (CMV) retinitis; decreasing (P < or = .05)
trends occurred for 11 OIs (MAC disease, PCP, CMV retinitis, Kaposi's sarcoma,
esophageal candidiasis, CMV disease, extrapulmonary cryptococcosis, toxoplasmic
encephalitis, tuberculosis, chronic herpes simplex, and disseminated
histoplasmosis). Among IDUs, the most frequent OIs were PCP, MAC disease, and
esophageal candidiasis; decreasing trends occurred for 5 OIs (PCP, esophageal
candidiasis, tuberculosis, chronic herpes simplex, and chronic cryptosporidiosis)
and an increase occurred in recurrent pneumonia. The differences in trends for
MSM and IDUs may be due to differences in medical care and adherence to
preventive medications.
PMID- 9652431
TI - Initial (6-month) results of three-times-weekly azithromycin in treatment
regimens for Mycobacterium avium complex lung disease in human immunodeficiency
virus-negative patients.
AB - Two consecutive, open, prospective trials of intermittent azithromycin (600 mg),
usually given Monday, Wednesday, and Friday (TIW) for Mycobacterium avium complex
(MAC) lung disease were initiated in human immunodeficiency virus-negative
patients. Regimen A consisted of TIW azithromycin and daily ethambutol (15
mg/kg/day), daily rifabutin (300 mg/day), and initial twice weekly (BIW)
streptomycin. Regimen B consisted of TIW azithromycin, TIW ethambutol (25
mg/kg/dose), TIW rifabutin (600 mg/dose), and initial BIW streptomycin. Of 19
patients enrolled in regimen A who completed at least 6 months of therapy, 14
(74%) had sputum samples become culture-negative. Of 39 patients enrolled in
regimen B who completed at least 6 months of therapy, 24 (62%) had sputum
conversion. These sputum conversion rates are comparable to previous rates at 6
months in patients receiving daily clarithromycin- or azithromycin-containing
regimens. No resistance to azithromycin emerged with either regimen. This is the
first study to demonstrate the efficacy of intermittent administration of
medication for MAC lung disease.
PMID- 9652432
TI - Expression of chemokines and induction of rapid cell death in human blood
neutrophils by Mycobacterium tuberculosis.
AB - To elucidate the role of neutrophils in the early inflammatory response to
mycobacterial infection, expression of chemokines interleukin (IL)-8 and
macrophage inflammatory protein-1alpha (MIP-1alpha) was examined in human blood
neutrophils in response to the lipopolysaccharide (LPS) of Escherichia coli,
which induces acute inflammation, or to Mycobacterium tuberculosis or purified
protein derivative (PPD), which induce chronic mycobacterial inflammation.
Neutrophils stimulated with LPS, M. tuberculosis, or PPD expressed both IL-8 and
MIP-1alpha. Expression of IL-8 and MIP-1alpha was lower after stimulation with M.
tuberculosis or PPD than after stimulation with LPS, but the kinetics of
expression did not differ significantly. In contrast, both M. tuberculosis and
PPD with tumor necrosis factor-alpha induced neutrophils to undergo rapid cell
death, which might remove neutrophils and activate macrophages at sites of
mycobacterial inflammation. The findings suggest that neutrophils play important
roles in the host defense against mycobacterial infection.
PMID- 9652433
TI - Cellular immune responses to four doses of percutaneous bacille Calmette-Guerin
in healthy adults.
AB - To explore the hypothesis that low-dose immunization might induce preferential
Th1 cell immunity, 76 adults were vaccinated with one of four doses of bacille
Calmette-Guerin (BCG): The doses contained very low (1.6 x 10(5) cfu), low (3.2 x
10(6) cfu), standard (1.6 x 10(8) cfu), or high (3.2 x 10(8) cfu) levels of BCG.
Delayed-type hypersensitivity responses occurred 8 weeks after vaccination in 10%
of persons given very low or low doses of BCG, compared with 95% and 100% of
persons given standard or high doses, respectively. Lymphoproliferative
responses, which were increased only for high-dose vaccinees, peaked 2 weeks
after vaccination and were directed chiefly against Mycobacterium tuberculosis
secreted proteins, particularly the antigen 85 complex. Significant increases in
mycobacteria-specific interferon-gamma expression were present 16 weeks after
vaccination only for persons given standard or high doses of BCG. Percutaneous
BCG appears capable of inducing a temporary Th1-like immune response, but
standard or higher dosages are required.
PMID- 9652434
TI - Protein F1 is required for efficient entry of Streptococcus pyogenes into
epithelial cells.
AB - It was recently reported that strains of Streptococcus pyogenes are capable of
inducing entry of the bacterium into epithelial cells; however, nothing is known
regarding the gene(s) and the underlying mechanism(s) involved. Using isogenic
mutants of S. pyogenes JRS4 strain that are defective in the expression of each
of the surface proteins F1 and M6, it was demonstrated that both are required for
efficient internalization. Expression of F1 on the surface of a poorly invading
S. pyogenes strain significantly enhances its internalization efficiency. Protein
F1-mediated internalization is inhibited by UR, the nonrepetitive fibronectin
binding domain of this protein, and to a lesser extent, by the repetitive
fibronectin-binding domain, RD2. Polyclonal anti-human fibronectin antibodies
completely abolish F1-mediated internalization; increasing fibronectin
concentrations result in a significant enhancement of bacterial uptake. The
findings shown here suggest that protein F1 mediates streptococcal
internalization and that the M6 protein is required for more efficient entry of
the bacterium.
PMID- 9652435
TI - Penicillin-binding protein 5 sequence alterations in clinical isolates of
Enterococcus faecium with different levels of beta-lactam resistance.
AB - The low-affinity penicillin-binding protein (PBP) 5 is the main beta-lactam
target and is responsible for resistance to this class of antibiotics in
Enterococcus faecium. The PBP 5 variants of 15 clinical isolates (including 8
resistant to vancomycin) with different levels of beta-lactam resistance were
analyzed. Most of the highly beta-lactam-resistant isolates produced small
quantities of PBP 5 of low affinity. This was associated with particular amino
acid substitutions: an Ala or Ile for Thr-499, a Glu for Val-629, and a Pro for
Ser-667. A change of Met-485 to Thr or Ala (adjacent to the conserved SDN box)
was observed in isolates with MICs of ampicillin of 64 or 128 microg/mL,
respectively. In the 2 most resistant isolates, with MICs of ampicillin of 256
microg/mL, an additional Ser was present just after Ser-466. Thus, particular
point mutations in PBP 5 and combinations thereof may lead to high-level beta
lactam resistance in E. faecium.
PMID- 9652436
TI - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New
York hospitals. MRSA Collaborative Study Group.
AB - Consecutive single-patient methicillin-resistant Staphylococcus aureus (MRSA)
isolates (270) from 12 hospitals (8217 beds) in metropolitan New York City were
collected during May 1996. In 11 of 12 hospitals, MRSA was most frequent in the
general medical services. DNA typing ("fingerprinting") revealed that
mecA:Tn554:PFGE (pulsed-field gel electrophoresis) type I:A:A accounted for 113
(42%) of 270 isolates, was detected in all hospitals, and was the predominant
clone in 9. Thirteen of 15 I:E:F isolates were from 1 hospital, and the remaining
2 were from another hospital of the same health system. Type V:NH:E was isolated
from 22 (79%) of the 28 patients with AIDS, including 8 of 9 patients from an
additional hospital. Subtype V:NH:E2 was recovered from 11 patients, 9 of whom
had AIDS, including all 5 AIDS patients from one floor of a nursing home
affiliated with a third hospital. By using both mecA:Tn554 probes and PFGE, MRSA
clusters and outbreaks may be detected and provide a rationale for appropriate
infection control intervention.
PMID- 9652438
TI - Induction of apoptosis in normal human renal tubular epithelial cells by
Escherichia coli Shiga toxins 1 and 2.
AB - The cytotoxicity of Shiga toxin (Stx) 1 and Stx2 produced by Escherichia coli to
human renal cortical epithelial cells (HRCEC) in primary culture was
investigated. HRCEC express CD24, the marker of renal distal tubules, as well as
globotriaosyl ceramide/CD77, the receptor for Stxs. Binding of Stxs to HRCEC was
confirmed by positive staining with specific antibodies to Stxs. Treatment of
HRCEC with Stxs induced rapid cell death, which was reversed in the presence of
neutralizing antibody specific for Stx. DNA fragmentation was found to be
accompanied by Stx-mediated cell death in HRCEC, indicating that apoptosis was
part of the process. These data and previous reports indicate that a variety of
renal cell types, including tubular epithelial cells as well as glomerular
capillary endothelial cells, may be targets for Stx-mediated apoptosis, which
could contribute to the pathogenesis of hemolytic-uremic syndrome caused by Stx
producing E. coli infection.
PMID- 9652437
TI - A large outbreak of botulism: the hazardous baked potato.
AB - In April 1994, the largest outbreak of botulism in the United States since 1978
occurred in El Paso, Texas. Thirty persons were affected; 4 required mechanical
ventilation. All ate food from a Greek restaurant. The attack rate among persons
who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among
persons who did not eat the dip (relative risk [RR] = 13.8; 95% confidence
interval [CI], 7.6-25.1). The attack rate among persons who ate an eggplant-based
dip was 67% (6/9) compared with 13% (241189) among persons who did not (RR = 5.2;
95% CI, 2.9-9.5). Botulism toxin type A was detected from patients and in both
dips. Toxin formation resulted from holding aluminum foil-wrapped baked potatoes
at room temperature, apparently for several days, before they were used in the
dips. Consumers should be informed of the potential hazards caused by holding
foil-wrapped potatoes at ambient temperatures after cooking.
PMID- 9652439
TI - Enteroaggregative Escherichia coli as a potential cause of diarrheal disease in
adults infected with human immunodeficiency virus.
AB - Stools of 68 human immunodeficiency virus (HIV)-infected adults with diarrhea and
60 without diarrhea were examined for enteroaggregative Escherichia coli (EAggEc)
by HeLa cell adherence assay. EAggEc were present in stools of 30 patients with
and 18 without diarrhea (P = .05). CD4 cell counts of patients with EAggEc and
diarrhea were significantly lower than those of patients with EAggEc without
diarrhea (P = .02). There was no difference in the mean duration of diarrheal
symptoms or in the number of stools per day between patients with EAggEc and
those without. None of the EAggEc strains were positive by polymerase chain
reaction for adherence fimbria, but 11 strains were positive for EAggEc heat
stable toxin EAST/1. Of the EAggEc strains, 51% were resistant to trimethoprim
sulfamethoxazole and 65% were resistant to ampicillin. EAggEc may be a pathogen
in HIV-infected patients with diarrhea; HIV-infected patients with EAggEc appear
to be more symptomatic when HIV disease is more advanced.
PMID- 9652440
TI - Evaluation of an isogenic hemolysin-deficient mutant in the human model of
Haemophilus ducreyi infection.
AB - Haemophilus ducreyi causes the genital ulcerative disease chancroid. One putative
virulence factor of H. ducreyi is a pore-forming hemolysin that displays toxicity
against human fibroblasts and keratinocytes. In order to test the role of the
hemolysin in pathogenesis, an isogenic hemolysin-deficient mutant was
constructed, designated 35000HP-RSM1. The lipooligosaccharide, outer membrane
protein patterns, and growth attributes of 35000HP-RSM1 were identical to its
parent, 35000HP. Human subjects were challenged on the upper arm with the
isogenic isolates in a double-blinded, randomized, escalating dose-response
study. Pustules developed at a similar rate at sites inoculated with the mutant
or parent. The cellular infiltrate and bacterial load in lesions were also
similar. These results indicate the hemolysin does not play a role in pustule
formation. Due to the limitations of this model, the role of the hemolysin at
later stages of infection could not be determined.
PMID- 9652441
TI - Protection against experimental intraabdominal sepsis by two polysaccharide
immunomodulators.
AB - Two immunomodulating polysaccharides, poly-(1-6)-beta-glucotriosyl-(1-3)-beta
glucopyranose (PGG)-glucan and Bacteroides fragilis polysaccharide A (PS A), were
evaluated for the prevention of mortality and abscess formation associated with
experimental intraabdominal sepsis. Prophylactic treatment with a combination of
these compounds significantly reduced mortality (8% vs. 44% in the saline-treated
control group) and the incidence of abscesses (30% vs. 100% in the saline-treated
control group) after challenge with rat cecal contents. These compounds were also
effective when administered therapeutically after bacterial contamination of the
peritoneal cavity. PS A treatment conferred long-term protection against abscess
formation and resulted in significantly fewer total aerobes and anaerobes in the
peritoneal fluid of animals challenged with cecal contents. These data
demonstrate the usefulness of two immunomodulatory polysaccharides in preventing
experimental intraabdominal sepsis in the absence of antimicrobial therapy and
may represent a new adjunct to antibiotic regimens currently used to prevent
clinical cases of this disease.
PMID- 9652442
TI - Vacuolating toxin production in clinical isolates of Helicobacter pylori with
different vacA genotypes.
AB - A vacuolating cytotoxin encoded by vacA in Helicobacter pylori is known as a
potential virulent determinant. The relationship between different vacA alleles,
vacuolating ability, and H. pylori-related diseases was investigated. Genetic
analysis of 119 isolates from Taiwanese patients revealed that 104 strains were
s1a/m2, 13 strains were characterized as the s1a/m1T type, which was more
homologous to the s1a/m1 strains, and 2 were characterized as the s1a/m1Tm2
chimeric type. Production of high-grade cytotoxin among 11 strains with s1a/m1T
was higher (72.7%) than among 66 strains with s1a/m2 (21.2%) (P < .01). Peptic
ulcer occurred in 76.9% of 13 patients with s1a/m1T strains compared with 46.2%
of 104 patients with s1a/m2 strains (P < .05). These results suggest that s1a/m1T
strains are associated with increased cytotoxic activity and higher ulcer
prevalence than are s1a/m2 strains.
PMID- 9652443
TI - Acid-tolerance response in Helicobacter pylori and differences between cagA+ and
cagA- strains.
AB - Helicobacter pylori cagA transcription and translation are maximal at pH 6 in
stationary phase. The aim of this study was to determine whether H. pylori has an
acid-tolerance response and whether that response is related to CagA expression,
by investigating whether preexposure to pH 5 or 6 improved survival of cells
subsequently exposed to pH 3. Cell number was determined after broth growth,
after exposure to pH 5, 6, or 7, and then after a 30-min exposure to pH 3 without
urea. H. pylori cells preexposed to pH 6 or 5 survived pH 3 exposure 100-fold
better than did cells preexposed to pH 7. Cells of cagA+ strains grown at pH 6
for 48 h, which induced maximal CagA expression, were significantly more
susceptible to pH 3 than were wild type cagA- strains or isogenic cagA-
knockouts. Thus, H. pylori strains possess a urea-independent acid-tolerance
response. Differential acid susceptibility may contribute to preferential
colonization of particular H. pylori strains in specific mucus layer niches.
PMID- 9652444
TI - Prevalence of vacuolating cytotoxin production and distribution of distinct vacA
alleles in Helicobacter pylori from China.
AB - Studies of Helicobacter pylori from the West have linked production of
vacuolating cytotoxin and a particular signal sequence (s1a) allele of the
underlying vacA gene to peptic ulcer disease (PUD). Among Chinese H. pylori, most
isolates from both PUD and gastritis patients were toxigenic (35/46 and 29/35,
respectively). Polymerase chain reaction and DNA sequencing showed that 95 of 96
isolates carried vacA s1a alleles. In the mid-region, 78 of 96 isolates carried
m2; 14 were m1-like but only 87% identical (DNA-level) to classical m1 and were
designated m1b; the other 4 were unusual hybrids (m1b-type proximal, m2-type
distal). Isolates with m1b and m1b-m2 alleles produced higher levels of
vacuolating activity than did isolates with m2 alleles (P < .01). There was no
association between any vacA allele and disease. These results suggest that the
composition of H. pylori gene pools varies geographically and that other as-yet
unknown polymorphic H. pylori genes are important in PUD.
PMID- 9652445
TI - Genetic basis for protection against experimental vaginal candidiasis by
peripheral immunization.
AB - In these studies, significant protection against experimental vaginal candidiasis
after a subcutaneous immunization with Candida albicans extract was achieved in
BALB/c mice but not in C57BL/6 (B6) mice. Protection from vaginal candidiasis was
transferred to naive BALB/c mice by a population of spleen cells derived from
immunized BALB/c mice. Removal of CD3 or CD4 but not CD8 T cells before transfer
completely abrogated resistance to vaginal candidiasis. Recombinant inbred (RI)
strains of mice derived from BALB/c and B6 strains were used for mapping loci
that might be responsible for regulating vaginal protection after subcutaneous
immunization. Linkage analysis using microsatellite-based genome mapping in these
RI strains revealed four candidate loci on chromosomes 3, 7, 8, and 18 that
exhibit statistically significant linkage to the strain distribution pattern.
These results may contribute to the understanding of host genetic factors
controlling the immune response to vaginal infections.
PMID- 9652446
TI - Recognition of Pneumocystis carinii antigens by local antibody-secreting cells
following resolution of P. carinii pneumonia in mice.
AB - To examine the repertoire of Pneumocystis carinii antigens recognized by antibody
secreting B cells from tracheobronchial lymph nodes isolated immediately
following recovery from P. carinii pneumonia, monoclonal antibodies (MAbs) were
produced from these cells. In contrast to previous studies of systemic immunity,
P. carinii gpA was not the immunodominant antigen recognized by these B cells.
Forty-nine (91%) of 54 P. carinii-specific hybridoma culture supernatants reacted
with P. carinii antigens other than gpA. Many of the resulting MAbs recognized a
previously uncharacterized antigen expressed on the surface of both cysts and
trophozoites. Western blotting using one of the cloned MAbs revealed reactivity
with a broad range of antigenic material, with the most intense reactivity in the
50- to 65-kDa region of the blot. The antigens identified by these MAbs merit
further investigation regarding protective immunity to P. carinii because they
were recognized by B cells in the context of recovery from P. carinii pneumonia.
PMID- 9652447
TI - Molecular methods for the diagnosis of genital ulcer disease in a sexually
transmitted disease clinic population in northern Thailand: predominance of
herpes simplex virus infection.
AB - A multiplex polymerase chain reaction (M-PCR) assay that simultaneously detects
the three major causes of genital ulcer disease (GUD), Haemophilus ducreyi,
Treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens
for 38 sequential patients with GUD at a Thai sexually transmitted disease
clinic. Subjects received clinical diagnoses and syndromic treatment. Swab
specimens for H. ducreyi cultures and M-PCR were obtained. No H. ducreyi cultures
were positive. Of 38 M-PCR specimens, 31 (81.6%) were positive for HSV, 1 (2.3%)
for both HSV and T. pallidum, and none for H. ducreyi or T. pallidum alone; 6
(15.8%) were negative for all 3 pathogens. Clinical diagnoses corresponded poorly
to M-PCR findings; none of 5 suspected cases of chancroid were positive by M-PCR
and none of 1 for syphilis, but 21 of 24 suspected herpes lesions were confirmed
by M-PCR. Human immunodeficiency virus infection status was known for 24 of 38
subjects; 11 (45.8%) were seropositive, and all 11 had HSV by M-PCR. HSV appeared
to be the most common pathogen overall.
PMID- 9652448
TI - Induction of interleukin-12 production in chronic hepatitis C virus infection
correlates with the hepatocellular damage.
AB - Interleukin (IL)-12 plays an essential role in host defense against infectious
diseases. Serum IL-12 concentration and blood mononuclear cell production with or
without specific interferon (IFN)-gamma priming were investigated in 65 chronic
hepatitis C virus (HCV) patients and 25 healthy donors. HCV patients had higher
serum IL-12 levels (P = .004) and produced higher amounts after IFN-gamma priming
(P < .001) than donors. A subset of patients did not produce IL-12: They had
lower serum levels (P = .032) and showed signs of liver piecemeal necrosis less
frequently (P = .011). Patients with greater liver necroinflammatory activity
produced more IL-12 than patients with minimal or mild activity and donors (P <
.01). During IFN-alpha therapy for 16 HCV patients, individuals with end-of
treatment alanine aminotransferase normalization and clearance of viremia had
higher serum levels and produced more IL-12 than those who did not (P < .05).
These results suggest a role for IL-12 in the immunopathogenesis and outcome of
HCV infection.
PMID- 9652449
TI - Association of rare human papillomavirus types with genital premalignant and
malignant lesions.
AB - Due to the limited number of reports concerning their association with particular
dysplastic and neoplastic lesions, the oncogenic potential of so-called rare or
novel human papillomavirus (HPV) types is still unclear. Cytologic smears or
biopsy specimens from 538 patients were analyzed for dysplastic or neoplastic
lesions and HPV infection. The HPV detection and typing system utilized allowed
identification of all mucosal HPVs amplifiable by L1 polymerase chain reaction.
Considering only patients infected with a single HPV type (n = 329), rare or
novel HPVs (HPV-59, HPV-61, HPV-62, HPV-66, HPV-70, HPV-73, MM4, MM7, MM8,
CP6108, and CP8304) were detected in 28% of normal specimens (n = 46), none of
condylomatous lesions (n = 44), 12% of low-grade squamous intraepithelial lesions
(SILs) (n = 42), 8% of high-grade SILs (n = 142), and 4% of cervical cancers (n =
54). Prevalence and oncogenic potential of distinct rare HPV types seems to be
higher than previously assumed.
PMID- 9652450
TI - No evidence for persistent enterovirus infection in patients with end-stage
idiopathic dilated cardiomyopathy.
AB - Persistence of enteroviruses in heart tissue has been implicated in the etiology
of idiopathic dilated cardiomyopathy (IDC). Therefore, we determined the
prevalence of enterovirus RNA in heart tissue from patients with end-stage IDC.
During heart transplantation, 287 transmural biopsy specimens were aseptically
collected from the explanted hearts of 38 patients with IDC and of 39 patients
with cardiac failure of known cause. A nested polymerase chain reaction with
general specificity for enteroviruses was used to screen for the presence of
enterovirus RNA in the heart tissue samples. No enterovirus RNA was detected in
any of the 287 heart biopsy specimens. These findings lead to a conclusion that
enteroviruses do not persist in heart tissue from patients with end-stage IDC,
nor with other heart diseases of known cause.
PMID- 9652452
TI - Disco fever: epidemic meningococcal disease in northeastern Argentina associated
with disco patronage.
AB - Neisseria meningitidis is a leading cause of adult meningitis worldwide. From 5
to 14 August 1996, 8 cases of meningococcal disease occurred in Corrientes city
(population 306,000) in northeastern Argentina. Those infected ranged in age from
15 to 45 years (median, 18.5). To determine risk factors for infection, a case
control study was done. Infecting isolates were serogrouped and underwent
phenotyping by multilocus enzyme electrophoresis (MLEE) and pulsed-field gel
electrophoresis (PFGE). Those infected were significantly more likely than those
not infected to have had exposure to passive or active cigarette smoke or to have
attended a particular disco. Isolates available from 6 case-patients were all
serogroup C; all had identical MLEE and PFGE patterns. These data suggest that
dance clubs or discos may be a focus of transmission of N. meningitidis among
young people.
PMID- 9652451
TI - Quantification of CD8+ T lymphocytes responsive to human immunodeficiency virus
(HIV) peptide antigens in HIV-infected patients and seronegative persons at high
risk for recent HIV exposure.
AB - The combination of a tumor necrosis factor (TNF)-alpha enzyme-linked immunospot
(ELISPOT) assay and computer-assisted video image analysis was used to detect and
quantitate in peripheral blood CD8+ T cells reactive with known human
immunodeficiency virus type 1 (HIV-1) peptide antigens presented by HLA-A2 or HLA
A3. T lymphocyte responsiveness to at least one HIV peptide was found in 10 (83%)
of 12 HIV-1-infected patients and in 5 (45%) of 11 persons who had no serologic
and virologic signs of HIV infection but who were at high risk for recent sexual
exposure to HIV-1. CD8+ T cells responding to HIV-1 peptides were observed in
none of 11 HIV-seronegative donors without a history of HIV exposure. ELISPOT
assays are relatively fast and easy to perform and appear to reliably detect T
cell reactivity due to previous exposure to HIV. These findings support the use
of the ELISPOT assay for monitoring T cell responsiveness to HIV peptides.
PMID- 9652453
TI - Circulating endotoxin during initial antibiotic treatment of severe gram-negative
bacteremic infections.
AB - The impact of antibiotics on total endotoxemia and circulating tumor necrosis
factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe
bacteremic sepsis or septic shock due to gram-negative species was investigated.
Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and
4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0
(median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL;
interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4
(median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell
between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at
H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that
endotoxemia is not increased by antibiotherapy of severe gram-negative
bacteremia.
PMID- 9652455
TI - A guinea pig model for Q fever endocarditis.
AB - A new model of experimental endocarditis, using electrocoagulation of native
aortic valves, was used for the study of Q fever endocarditis. In the 20 guinea
pigs electrocoagulated and inoculated with Coxiella burnetii Nine Mile phase I
strain, 10 presented with infective endocarditis. Of these, 7 died spontaneously.
All guinea pigs with endocarditis presented with blood cultures positive for C.
burnetii, and C. burnetii antigen was found in their cardiac valves. Positive
blood cultures or valvular immunopositive cells were not identified in either
nonelectrocoagulated or noninoculated controls. This experimental model
demonstrates that Q fever in an animal with previously damaged valves results in
endocarditis. It could provide a new tool for the investigation of
pathophysiology and antibiotic therapy for Q fever endocarditis.
PMID- 9652454
TI - High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells
in patients with cardiovascular disease and in middle-aged blood donors.
AB - Nested polymerase chain reaction (nPCR) demonstrated the presence of Chlamydia
pneumoniae-specific DNA in peripheral blood mononuclear cells (PBMC). PBMC
samples were obtained from 103 consecutive patients (62 male, 41 female) aged 22
85 years (mean, 64) admitted for coronary angiography because of suspected
coronary heart disease and from 52 blood donors (43 male, 9 female) aged 40-64
years (mean, 49). Of the 101 evaluable patients, 60 (59%) were identified by nPCR
assay as C. pneumoniae DNA carriers; C. pneumoniae-specific
microimmunofluorescence (MIF) serology confirmed exposure to the bacterium in 57
(95%) of the 60 nPCR-positive patients. Among the 52 blood donors, the nPCR assay
identified 24 (46%) C. pneumoniae DNA carriers, all of whom were positive by C.
pneumoniae-specific serology. Thirty-two patients (32%) and 23 blood donors (44%)
were MIF antibody-positive but repeatedly nPCR-negative; Bartonella henselae- or
Bartonella quintana-specific antibodies were not detected among any of these
subjects. In this study, C. pneumoniae DNA was common in PBMC of patients with
coronary heart disease and in middle-aged blood donors.
PMID- 9652456
TI - Detection of Onchocerca volvulus infection by O-150 polymerase chain reaction
analysis of skin scratches.
AB - The standard assay for onchocerciasis diagnosis is microscopic detection of
parasites in skin snips. Skin snipping is painful and may potentially transmit
bloodborne infections. Thus, an alternative method for the diagnosis of
onchocerciasis that does not require skin snipping is needed. A polymerase chain
reaction (PCR)-based assay was shown to detect the presence of parasite DNA in
superficial skin scrapings. Detection of parasite DNA in both skin snips and skin
scratches was found to be more sensitive for detecting low-density infections
than was microscopic examination of skin snips. The skin scratch PCR assay is
minimally invasive and painless and does not present the risk of transmitting
bloodborne infections. These properties make the skin scratch an attractive
alternative to the skin snip for detecting O. volvulus infection.
PMID- 9652457
TI - Humoral immune responses of Africans to cysteine protease-related antigens of
Plasmodium falciparum.
AB - The Plasmodium falciparum serine repeat antigen (SERA) and serine repeat protein
homologue (SERPH) contain highly conserved domains that appear to encode cysteine
proteases or related proteins. Humoral immune responses against the protease
domains of SERA and SERPH were evaluated. Malaria-immune Africans, but not
nonimmune controls, demonstrated potent humoral responses against the protease
domains. As the SERA and SERPH protease domains are likely accessible to
circulating antibody, these results suggest that humoral responses to the domains
may contribute to antimalarial immunity.
PMID- 9652458
TI - Chemotherapy accelerates the development of acquired immune responses to
Schistosoma haematobium infection.
AB - Treatment of 41 Schistosoma haematobium-infected children, 5-16 years old, with
the drug praziquantel induced a switch from a predominantly IgA-specific antibody
response to a predominantly IgG1 response within 12 weeks. A cross-sectional
survey suggests that the same switch occurs naturally, but over several years, as
children age (n = 251). The switch may be driven by alterations in cytokine
levels in response to the release of antigens by dead or damaged parasites.
Adults are more resistant to schistosome infection than children, and the switch
to an "adult" response suggests that praziquantel treatment may have an
immunizing effect, with benefits extending beyond a transient reduction in levels
of infection.
PMID- 9652459
TI - False-negative fluorescent treponemal tests and confirmation of syphilis
infection.
PMID- 9652460
TI - Presidential address: the Yorpy principle.
PMID- 9652461
TI - Initial experience with endovascular aneurysm repair: comparison of early results
with outcome of conventional open repair.
AB - PURPOSE: To determine the safety, effectiveness, and problems encountered with
endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with
endoluminal stent grafts was examined and compared with outcome for a matched
concurrent control group undergoing conventional operative repair of AAA.
METHODS: Over a 3-year period, 30 patients underwent attempts at endovascular
repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8
were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined
with femorofemoral bypass. Most of the procedures were performed in the past year
because the availability of bifurcated and aortoiliac endografts markedly
expanded the percentage of patients with AAA who might be treated with
endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean
value of 11 months. RESULTS: Endovascular procedures demonstrated significant
advantages with respect to reduced blood loss (408 versus 1287 ml), use of an
intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus
10.3 days), and quicker recovery (11 versus 47 days). Although the total number
of postoperative complications was identical for the two groups, the nature of
the complications differed considerably. Local and vascular complications
characteristic of endovascular repair could frequently be corrected at the time
of the procedure and tended to be less severe than systemic or remote
complications, which predominated among the open surgical repair group. On an
intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with
endoluminal repair. The seven (23%) failures were attributable to two immediate
conversions caused by access problems, three persistent endoleaks, one late
conversion caused by AAA expansion, and one late rupture. CONCLUSIONS: Although
less definitive than those for conventional operations, these early results
suggest that endovascular AAA repair offers considerable benefits for appropriate
patients. The results justify continued application of this method of AAA repair,
particularly in the treatment of older persons at high risk.
PMID- 9652462
TI - Penetrating ulcer of the thoracic aorta: what is it? How do we recognize it? How
do we manage it?
AB - BACKGROUND: Although classic type A and B aortic dissections have been well
described, less is known about the natural history of penetrating atherosclerotic
ulcers of the thoracic aorta. This study differentiates penetrating ulcer from
aortic dissection, determines the clinical features and natural history of these
ulcers, and establishes appropriate correlates regarding optimal treatment.
METHODS: A retrospective review of patient records and imaging studies was
conducted with 198 patients with initial diagnoses of aortic dissection (86 type
A, 112 type B) at our institution from 1985 to 1997. RESULTS: Of the 198
patients, 15 (7.6%) were found to have a penetrating aortic ulcer on re-review of
computed tomographic scans, magnetic resonance images, angiograms,
echocardiograms, intraoperative findings, or pathology reports. Two ulcers
(13.3%) were located in the ascending aorta; the other 13 (86.7%) were in the
descending aorta. In comparison with those with type A or B aortic dissection,
patients with penetrating ulcer were older (mean age 76.6 years, p = 0.018); had
larger aortic diameters (mean diameter 6.5 cm); had ulcers primarily in the
descending aorta (13 of 15 patients, 86.7%); and more often had ulcers associated
with a prior diagnosed or managed AAA (6 of 15 patients, 40.0%; p = 0.0001). Risk
for aortic rupture was higher among patients with penetrating ulcers (40.0%) than
patients with type A (7.0%) or type B (3.6%) aortic dissection (p = 0.0001).
CONCLUSIONS: Accurate recognition and differentiation of penetrating ulcers from
classic aortic dissection at initial presentation is critical for optimal
treatment of these patients. For penetrating ulcer, the prognosis may be more
serious than with classic type A or B aortic dissection. Surgical management is
advocated for penetrating ulcers in the ascending aorta and for penetrating
ulcers in the descending aorta that exhibit early clinical or radiologic signs of
deterioration.
PMID- 9652463
TI - Carotid endarterectomy after NASCET and ACAS: a statewide study. North American
Symptomatic Carotid Endarterectomy Trial. Asymptomatic Carotid Artery Stenosis
Study.
AB - PURPOSE: Since the North American Symptomatic Carotid Endarterectomy Trial
(NASCET) and the Asymptomatic Carotid Artery Stenosis Study (ACAS) established
the efficacy of carotid endarterectomy at large academic centers, there have been
two community-based studies of outcomes after this operation. The purpose of this
study was to perform a statewide survey to evaluate postoperative morbidity and
mortality after carotid endarterectomy among patients throughout Maine. METHODS:
A statewide registry was established to collect prospective data on carotid
operations from January 1 to December 31, 1995. All surgeons and hospitals in the
state were solicited to participate. All carotid endarterectomies were intended
to be included; the only exclusion criterion was out-of-state residence.
Comorbidities, preoperative studies, surgical indications, operative technique,
and postoperative outcomes were analyzed. State administrative data were used to
assess registry coverage. RESULTS: Ten of 17 hospitals participated, and 58% of
all carotid endarterectomies performed in the state were included. Three hundred
sixty-four operations were entered into the registry. Forty-four percent of the
operations were performed for transient ischemic attack, 37% for asymptomatic
stenosis, and 19% for stroke. The postoperative stroke rate was 2.5% with a total
neurologic complication rate of 4.7% (transient ischemic attack and stroke).
There was one postoperative death (mortality rate 0.3%). Patients with symptoms
had a higher incidence of postoperative stroke (4.0% vs 0% asymptomatic; p <
0.05) and transient ischemic attacks (3.8% vs 0.8% asymptomatic). Hospital stroke
rates varied from 0% to 7%. Stroke rate did not differ significantly between low
volume hospitals (2 to 28 patients/year, 3.3%) and high-volume hospitals (29 to
101 patients/year, 2.3%) or between low-volume surgeons (fewer than 11
operations/year, 1.7%) and high-volume surgeons (more than 12 operations/year,
2.4%). Among 26 reporting surgeons, stroke rate varied from 0% to 10%; the
absolute number of strokes per surgeon varied between zero and two. CONCLUSION:
The statewide registry showed a postoperative stroke plus death rate of 2.8%,
comparable with the NASCET and ACAS findings. Although this study had inherent
limitations, the results from one state, including a variety of community
practices, achieved results comparable with those of landmark trials.
PMID- 9652464
TI - Cerebral microembolism and ischemic changes associated with carotid
endarterectomy.
AB - PURPOSE: The purpose of this study is to characterize microembolic signals (MS)
that occur during the various phases of carotid endarterectomy (CEA) and to
consider their relationship to postoperative changes on magnetic resonance
imaging (MRI). METHODS: This was a retrospective study of 76 patients who
underwent 78 carotid endarterectomies at a referral center. Perioperative
transcranial Doppler monitoring and MRI were performed before and after CEA. The
types of MS that occurred during phases of surgery were analyzed and compared
with MRI changes. RESULTS: We observed a clinical stroke in one patient (1.3%)
and ipsilateral small areas of silent ischemic change on seven postoperative MRI
studies (9.0%). In 95% of CEAs, MS were detected. Only those MS observed in the
recovery room that occurred at a rate of more than five per 15 minutes were
associated with postoperative MRI ischemic changes (p < 0.0001). CONCLUSIONS:
Ischemic changes on MRI after CEA are related to postoperative MS.
PMID- 9652465
TI - Percutaneous ultrasound guided thrombin injection: a new method for treating
postcatheterization femoral pseudoaneurysms.
AB - PURPOSE: Since its introduction in 1991, ultrasound guided compression repair of
postcatheterization femoral artery pseudoaneurysms has been shown to be
effective. Disadvantages of ultrasound guided compression repair include patient
discomfort during compression, inability to treat noncompressible
pseudoaneurysms, prolonged use of ultrasound equipment and personnel, limited
success with patients being treated with anticoagulants, and some early
recurrences. We conducted a prospective study to evaluate a new method of
treating femoral pseudoaneurysms, percutaneous ultrasound guided thrombin
injection. METHODS: Under duplex ultrasound guidance, a 22- or 25-gauge needle
was percutaneously positioned within the pseudoaneurysm. Without compressing the
pseudoaneurysm, 0.5 to 1 ml thrombin solution (1000 U/ml) was injected to induce
thrombosis. Early in the study, the procedure was modified to allow more than one
injection. After successful thrombosis, the patients were kept at rest in bed for
at least 1 hour. Duplex ultrasound examination was repeated in 1 to 4 days.
Distal pulses and ankle-brachial indexes were measured before and after the
procedure. RESULTS: Twenty of 21 consecutive pseudoaneurysms were successfully
treated with thrombin injection. Fifteen pseudoaneurysms thrombosed immediately
(<20 seconds) after one injection. The other five had partial thrombosis after
one injection and complete thrombosis immediately after a second injection. The
one failure occurred in a patient who had only one injection and then underwent
subsequent ultrasound guided compression repair, which failed. No patient
required sedation or analgesia during thrombin injection. There were no procedure
related complications and no recurrences. CONCLUSIONS: Percutaneous ultrasound
guided thrombin injection appears to be a safe and expeditious method for
treating postcatheterization femoral pseudoaneurysms. It has significant
advantages with respect to ultrasound guided compression repair or surgical
repair.
PMID- 9652466
TI - Fate of the contralateral leg after infrainguinal bypass.
AB - PURPOSE: To identify variables predictive of the need for future vascular
intervention in a leg contralateral to one currently undergoing infrainguinal
bypass. METHODS: We reviewed the records of 450 consecutively treated patients
undergoing infrainguinal bypass for occlusive disease to examine the outcome of a
previously untreated contralateral leg. Patients with coexistent contralateral
limb-threatening ischemia at the time of initial ipsilateral operation were
excluded, as were patients with bilateral disease who underwent a staged
contralateral procedure within 3 months of the ipsilateral operation. This
yielded a study cohort of 383 patients with no anticipated intervention in the
contralateral leg who were followed for a mean value of 38 months. Patient
survival and subsequent intervention in the contralateral leg were examined with
life-table and regression analysis. RESULTS: Mean age of the patients was 68
years; 60% were men; 54% had diabetes; and 50% had coronary artery disease. The
initial ipsilateral operation was performed for limb threat in 90% of instances.
Twenty percent of patients subsequently needed intervention in the contralateral
leg (infrainguinal bypass 83%, primary major amputation 17%). According to life
table analysis, 30% of patients needed intervention at 5 years, and the overall
survival rate was 51% at 5 years. Multivariate analysis indicated that the need
for future contralateral intervention was independently predicted with the
following four risk factors: diabetes (relative risk [RR] 2.4x), coronary artery
disease (RR 1.8x), lower initial ankle-brachial index (RR 2.1x with ankle
brachial index less than 0.7), and younger age (RR 2.2x if age less than 70
years). Regression models predicted the need for contralateral intervention for
only 8% of patients at 5 years when none of these risk factors was present but
for 67% when all risk factors were present. CONCLUSION: The fate of the
contralateral leg after infrainguinal bypass is affected by diabetes, coronary
artery disease, contralateral ankle-brachial index, and age at initial
ipsilateral bypass. The effect of these risk factors is additive in prediction of
the likelihood of future intervention. Knowledge of these factors may help
identify instances in which the contralateral greater saphenous vein will be
important for future limb salvage and also determine which patients need more
careful follow-up care.
PMID- 9652467
TI - Early outcome of in situ femorotibial reconstruction among patients with diabetes
alone versus diabetes and end-stage renal failure: analysis of 83 limbs.
AB - PURPOSE: Both end-stage renal disease and diabetes have been demonstrated to have
a negative effect on the outcome of infrainguinal arterial reconstruction,
primarily because of increased perioperative morbidity and wound complications.
This study was undertaken to determine whether the combination of these comorbid
factors affects the outcome of distal arterial reconstruction. METHODS: Eighty
three distal lower extremity arterial bypasses originating from the femoral
artery and terminating at the peroneal, anterior, or posterior tibial artery were
performed on 76 patients over a 5-year period at a tertiary care medical center.
Autogenous greater saphenous vein was used as the bypass conduit in all
instances. Combined inflow and composite vein procedures were excluded. RESULTS:
There was one perioperative death, for a mortality rate of 1.2%. The diabetes
mellitus (DM) plus end-stage renal disease (DM+ESRD) cohort displayed a
significantly lower 1-year primary patency rate compared with the diabetes
mellitus cohort, 53% versus 82% (p < 0.02). However, the limb salvage rate for
the DM+ESRD and DM cohorts during the same time interval were not significantly
different, 63% versus 84% (p < 0.06). The 52% 1-year survival rate for the
DM+ESRD cohort was strikingly lower than the 90% 1-year survival rate for the DM
cohort (p < 0.002). CONCLUSION: Despite the use of the optimal autogenous
conduit, the combination of diabetes and end-stage renal disease can be expected
to significantly decrease primary graft patency without affecting limb salvage.
The greatest effect of these comorbid factors is on patient survival.
PMID- 9652468
TI - Impact of a critical pathway on postoperative length of stay and outcomes after
infrainguinal bypass.
AB - PURPOSE: To determine the effect of a critical pathway on postoperative length of
stay and outcomes after infrainguinal bypass. METHODS: A critical pathway for
care of patients after infrainguinal bypass was introduced in December 1995 to
coordinate postoperative care at our institution. We compared care of 67
consecutively treated patients before institution of the pathway with care of 69
consecutively treated patients with the critical pathway in place. Data
collection was done by means of chart review. Univariate analyses were used to
identify differences between prepathway and postpathway patients and to identify
factors influencing postoperative length of stay. Multivariate analysis was used
to identify factors that influenced length of stay and to examine the effect of
use of the pathway after adjusting for other factors. RESULTS: Patients on the
pathway were similar to prepathway controls with respect to comorbid illnesses,
vascular risk factors, indications for surgical treatment, type of conduit, and
type of operation. Factors associated with longer postoperative stays included
distal anastomoses to tibial rather than popliteal vessels (p = 0.02),
preexisting cardiac disease (p = 0.005), postoperative complications (p =
0.0003), lower preoperative hematocrit (p = 0.01), and elevated preoperative
creatinine level (p = 0.006). Overall, pathway patients had somewhat shorter
postoperative lengths of stay (median value 7 days; range 2 to 29 days) than
prepathway patients (median value 6 days; range 2 to 35; p = 0.01), and the two
groups had similar frequencies of postoperative complications, readmission, and 6
month mortality. However, patients on the pathway were more likely to be
discharged to an intermediate-care facility rather than directly home. After 12
patients with extraordinarily prolonged postoperative stays were excluded,
multivariate analysis indicated that pathway patients had significantly shorter
postoperative stays (p = 0.001). However, the difference was not significant if
patients with extraordinarily long postoperative stays were included in the
analysis (p = 0.28). CONCLUSION: Use of a critical pathway was associated with a
modest decrease in postoperative length of stay for most patients. This was
accomplished without an adverse effect on readmission, complication, or mortality
rates. However, the decrease in stay may have been achieved primarily by
discharging more patients to intermediate-care facilities. The pathway did not
appear to have any effect when the subset of patients with extraordinarily long
stays because of complex medical problems was included.
PMID- 9652469
TI - Reduction of hospital resources utilization in vascular surgery: a four-year
experience.
AB - PURPOSE: Managed care whether through risk or through capitated contracts results
in reduction in resources, reduced length of hospital stay, and reduced
utilization of hospital resources (collectively referred to as resource
reductions). These resource reductions will become even more noticeable as a
greater proportion of Medicare patients who need vascular operations select a
managed-care senior product. We examined the results of a 4-year experience with
resource management in an academic vascular surgery practice during which best
practice plans were developed and implemented. METHODS: We analyzed hospital cost
data, which included both total hospital and intensive care unit length of stay,
average units per operation for laboratory, pharmacy, and radiology services and
operating room and direct hospital costs for 257 carotid endarterectomies
performed over fiscal years (FY) 1994, 1995, 1996, and 1997 (6 month data) and
175 infrainguinal bypass procedures performed during the same period. RESULTS:
For carotid endarterectomy, length of stay decreased 66% over the 4-year period
to an average of 2.07 days in FY97. Both radiology and pharmacy utilization were
reduced after the first year of institution of best practice plans (56% and 32%
respectively) with 4-year total reductions of 86% and 55% by FY97. The most
notable changes included elimination of routine postoperative laboratory testing,
use of aspirin rather than low-molecular-weight dextran, emphasis on oral rather
than intravenous vasoactive drugs, and routine use of duplex scanning alone
rather than angiography for diagnosis after FY94-95. The length of operating room
time for carotid endarterectomy remained relatively constant from FY94 to FY97.
As a result of these multiple factors, our study showed a 30% decrease in total
average direct hospital costs for carotid endarterectomy from $9974 to $7002 in
this 4-year period. Infrainguinal bypass graft procedures showed a progressive
decrease in total cost of 28% for patients without complications to $15,186 but
remained unchanged for those with complications. Laboratory use, pharmacy use,
and radiology use were not significantly different. CONCLUSIONS: Case management
for patients undergoing carotid endarterectomy and infrainguinal bypass grafting
involving an integrated team of vascular surgeons, surgical house staff, a
dedicated vascular nurse, and a social work case manager resulted in dramatic
reductions both in length of stay and hospital resource utilization. As these
costs decreased, operating room expenses assumed increasing importance. Operating
room costs account for 60% of the direct costs of carotid endarterectomy and a
comparable percentage for uncomplicated infrainguinal bypass grafting. Further
substantial reductions in direct hospital costs will depend primarily on
reductions in operating room costs, particularly those related to length of time
in the operating room.
PMID- 9652470
TI - Mesenteric and celiac duplex scanning: a validation study.
AB - PURPOSE: To validate the accuracy of previously established duplex ultrasound
criteria for > or =50% superior mesenteric artery (SMA) and celiac artery (CA)
stenosis by comparison with arteriography. METHODS: Duplex criteria established
retrospectively in our laboratory in 1991 identified an end-diastolic velocity
(EDV) > or =45 cm/sec, or no flow signal, as highly sensitive (100%) and specific
(92%) indicators for SMA stenosis > or =50% or occlusion. EDV was more accurate
(95%) than peak systolic velocity (PSV), which had a maximal accuracy of 86% at a
PSV > or =300 cm/sec, with low sensitivity (62%), but high specificity (100%).
For CA, accurate velocity thresholds were not identified, but we subsequently
noted that retrograde common hepatic artery flow direction from SMA collateral
was highly predictive of severe CA stenosis or occlusion. Since publication of
those findings, 243 mesenteric duplex scans were performed for clinical
evaluation of suspected chronic mesenteric ischemia. Angiographic confirmation
was available for a subset of 46. SMA and CA diameters were measured on lateral
aortograms by observers blinded to the duplex results, and the original duplex
diagnostic criteria were tested for accuracy. In addition, receiver operator
characteristic curve analysis was performed on the velocity data to identify the
most accurate velocity thresholds in the new data. RESULTS: Duplex was
technically adequate in 98% of SMA, 96% of CA, and 89% of hepatic arteries, and
arteriograms were adequate in 100% of SMA and 98% of CA. For the SMA, EDV > or
=45 cm/sec again provided the best sensitivity (90%), specificity (91%), positive
predictive value (90%), negative predictive value (91%), and overall accuracy
(91%). As in the retrospective study, PSV > or =300 cm/sec provided low overall
accuracy (81%), low sensitivity (60%), but high specificity (100%). Lowering the
PSV threshold improved sensitivity but reduced accuracy. For CA, retrograde
common hepatic artery flow direction was 100% predictive of severe CA stenosis or
occlusion. Velocity data in CA provided accuracy not found in the original study.
EDV > or =55 cm/sec or no flow signal had best overall accuracy (95%) with high
sensitivity (93%) and specificity (100%). PSV > or =200 cm/sec or no signal also
had excellent accuracy (93%), sensitivity (93%), and specificity (94%). In
addition, three of four anatomic anomalies were correctly identified by duplex.
These included one right hepatic and one common hepatic artery originating from
the SMA, and one common celiacomesenteric trunk. CONCLUSION: This validation
analysis confirms that duplex velocity criteria are accurate in the
identification of mesenteric occlusive disease. Retrograde common hepatic artery
flow direction correctly predicts severe CA stenosis or occlusion. Duplex
ultrasound may also identify mesenteric anatomic variants that can influence
study interpretation.
PMID- 9652471
TI - Telemedicine in vascular surgery: feasibility of digital imaging for remote
management of wounds.
AB - PURPOSE: Telemedicine coupled with digital photography could potentially improve
the quality of outpatient wound care and decrease medical cost by allowing home
care nurses to electronically transmit images of patients' wounds to treating
surgeons. To determine the feasibility of this technology, we compared bedside
wound examination by onsite surgeons with viewing digital images of wounds by
remote surgeons. METHODS: Over 6 weeks, 38 wounds in 24 inpatients were
photographed with a Kodak DC50 digital camera (resolution 756 x 504 pixels/in2).
Agreements regarding wound description (edema, erythema, cellulitis, necrosis,
gangrene, ischemia, and granulation) and wound management (presence of healing
problems, need for emergent evaluation, need for antibiotics, and need for
hospitalization) were calculated among onsite surgeons and between onsite and
remote surgeons. Sensitivity and specificity of remote wound diagnosis compared
with bedside examination were calculated. Potential correlates of agreement,
level of surgical training, certainty of diagnosis, and wound type were evaluated
by multivariate analysis. RESULTS: Agreement between onsite and remote surgeons
(66% to 95% for wound description and 64% to 95% for wound management) matched
agreement among onsite surgeons (64% to 85% for wound description and 63% to 91%
for wound management). Moreover, when onsite agreement was low (i.e., 64% for
erythema) agreement between onsite and remote surgeons was similarly low (i.e.,
66% for erythema). Sensitivity of remote diagnosis ranged from 78% (gangrene) to
98% (presence of wound healing problem), whereas specificity ranged from 27%
(erythema) to 100% (ischemia). Agreement was influenced by wound type (p < 0.01)
but not by certainty of diagnosis (p > 0.01) or level of surgical training (p >
0.01). CONCLUSIONS: Wound evaluation on the basis of viewing digital images is
comparable with standard wound examination and renders similar diagnoses and
treatment in the majority of cases. Digital imaging for remote wound management
is feasible and holds significant promise for improving outpatient vascular wound
care.
PMID- 9652472
TI - Early operative intervention after thrombolytic therapy for primary subclavian
vein thrombosis: an effective treatment approach.
AB - PURPOSE: Effective treatment of primary subclavian vein thrombosis focuses on
restoration of venous patency, relief of intrinsic stenosis, and decompression of
the thoracic inlet. The appropriate method and timing for surgery, however, have
not been not well defined. We conducted a study to determine an acceptable
treatment approach. METHODS: A retrospective review evaluated 11 patients seen at
our institution in an 8-year period. Seven patients were male and four were
female, with an average age of 30 years (range 15 to 54 years). Two patients who
had symptomatic stenosis without occlusion were omitted from the study. All
patients with occlusion received urokinase therapy and underwent surgical
decompression within 5 days of thrombolytic therapy. Five percutaneous
transluminal angioplasties were attempted before operative intervention. Eleven
decompressions were performed, including nine first-rib resections and two
scalenectomies. Five operative venous procedures, consisting of thrombectomy with
patch closure (n = 3) and bypass (n = 2), and seven venolysis procedures were
performed. All patients received coumadin for 3 to 6 months after the operation.
RESULTS: Urokinase therapy established wide venous patency in nine of the 11
extremities treated, with the remaining two requiring thrombectomy for residual
thrombus at the time of operation. One patient who underwent transluminal
angioplasty before the operation had rethrombosis, and the remaining four showed
no improvement in venous stenosis after the intervention. Eight of nine
extremities treated by first-rib resection and one of two treated by scalenectomy
were free of residual symptoms at follow-up. CONCLUSIONS: Preoperative use of
percutaneous balloon angioplasty is ineffective and should be avoided in this
setting. Surgical intervention within days of thrombolysis obviates the need for
interim oral anticoagulation and enables patients to return to normal activity
sooner.
PMID- 9652473
TI - Patients with venous stasis ulceration have increased monocyte-platelet
aggregation.
AB - PURPOSE: Leukocyte activation has been implicated in the pathogenesis of venous
stasis ulceration, but the involvement of activated platelets and leukocyte
platelet aggregates has not been previously investigated. The purpose of this
study was to determine whether patients with venous stasis ulceration have
increased platelet activation and a propensity toward formation of leukocyte
platelet aggregates. METHODS: Blood was drawn from the superficial veins of the
leg just proximal to a venous stasis ulcer and from an antecubital vein in 14
patients with venous stasis ulceration. Blood was also drawn from the antecubital
vein of 14 volunteers without evidence of venous disease. Whole-blood flow
cytometry was used to analyze the samples before and after activation with a
panel of agonists for evidence of platelet activation and the formation of
leukocyte-platelet aggregates. RESULTS: Patients with venous stasis ulceration
had a greater number of monocyte-platelet aggregates in both the arm and leg
samples than did the control subjects (p < 0.01). Furthermore, antecubital blood
samples from patients with venous stasis ulceration stimulated with either
thrombin-receptor agonist peptide, adenosine diphosphate, or phorbol myristate
acetate formed more monocyte-platelet aggregates than did control samples (p <
0.05). No differences in platelet activation or neutrophil-platelet aggregate
formation were noted among the three sample groups. CONCLUSIONS: Patients with
venous stasis ulceration have an increase in the number of monocyte-platelet
aggregates in systemic venous blood as well as in venous blood adjacent to a
venous stasis ulcer, implicating the monocyte as the leukocyte involved in the
pathogenesis of venous stasis ulceration. No association was identified between
the presence of a venous stasis ulcer and either neutrophil-platelet aggregation
or the activation of individual platelets. Because platelet activation is
necessary for the formation of monocyte-platelet aggregates, these data also
suggest that monocyte-platelet aggregation is a more sensitive marker for in vivo
platelet activation than is the identification of individual activated platelets.
PMID- 9652474
TI - Evaluation of a novel hirudin-coated polyester graft to physiologic flow
conditions: hirudin bioavailability and thrombin uptake.
AB - PURPOSE: Our laboratory has developed methods required to covalently bind
recombinant hirudin (rHir) to the surface of polyester vascular grafts. Using
alkaline hydrolysis of the polyester surface, carboxyl-binding sites are created
on the outer periphery of each fiber. A series of static, in vitro experiments
have demonstrated that surface-bound rHir rapidly removes and inhibits activated
human alpha-thrombin from the reaction system; however, the performance of this
modified graft material under physiologic flow conditions was undefined. METHODS:
An in vitro flow loop was used to evaluate structural stability of the 125I-rHir
and 131I-albumin covalently bound to the surface of 6 mm interior diameter
crimped polyester grafts exposed to either constant flow (n = 4; shear rate, 300
sec(-1)) or pulsatile flow (n = 4; maximum shear rate, 780 sec(-1)) conditions
for a 7-day period. In a separate series of experiments, the kinetics of thrombin
rHir interaction were evaluated through perfusion of 125I-rHir-coated grafts (n =
6) with 131I-thrombin for a 27-hour period under constant flow conditions.
Identically prepared 125I-albumin-coated grafts (n = 3) were used as controls.
RESULTS: Results of the stability experiments were independent of flow
conditions, demonstrating moderate loss of both proteins, with rHir and albumin
losses of 52.1% and 19.9% under constant flow and 49.1% and 21.6% under pulsatile
flow, respectively. With results comparable with those of previous static
experiments, rHir-coated grafts were significantly more effective at removing
thrombin from the perfusion stream with 131I-thrombin binding densities of 3.08
+/- 0.61 and 0.64 +/- 0.04 NIHU/cm2 (p < 0.01) for rHir-coated and albumin-coated
grafts, respectively. Estimates of the total amount of thrombin inactivated
during the perfusion period similarly demonstrated a marked difference between
the rHir-coated and control graft segments (125 +/- 8 vs. 3 +/- 14 NIHU; p <
0.005). CONCLUSIONS: These in vitro flow results illustrate that polyester grafts
with covalently bound rHir can provide significant reductions in local thrombin
concentration under physiologic flow conditions, and can serve as a foundation
with which to understand the performance of these grafts when implanted in vivo
under physiologic flow and shear rates.
PMID- 9652475
TI - The differential effect of contrast agents on endothelial cell and smooth muscle
cell growth in vitro.
AB - PURPOSE: This study was designed to evaluate the effects of ionic and nonionic
contrast agents on endothelial cell (EC) and smooth muscle cell (SMC)
proliferation, and to determine the role of osmolality as the etiology of these
effects. METHODS: Cultured bovine aorta EC and SMC were exposed to ionic
(iothalamate meglumine) or nonionic (ioversol or iopamidol) contrast, or varying
osmolar solutions of mannitol, for periods of 1, 3, 5, 10, or 20 minutes. Cells
were then incubated in growth media at 37 degrees C and proliferation and
structure were assessed 1, 3, 5, and 7 days later. RESULTS: Both EC and SMC
showed decreased proliferation after brief exposure to both ionic and nonionic
contrast. Proliferation was markedly decreased at 24 hours after exposure, and
began to recover by day 3 after exposure. EC showed a significant decrease up to
7 days after exposure to ionic contrast (p < 0.03), whereas SMC showed a
significant decrease up to 7 days after exposure to nonionic contrast (p <
0.001). The decrease in proliferation was directly dependent on the length of
exposure to the contrast and the concentration of the contrast. EC proliferation
decreased in proportion to increasing osmolality of the test solution (p < 0.05).
SMC proliferation did not show a decrease proportional to osmolality. No change
was observed in cell viability as assessed by LDH activity studies. After
contrast exposure, bare areas with no cells present were noted in the previously
confluent EC and SMC culture wells. Cell structure was altered immediately after
exposure to contrast, with normal structure recovered by 24 hours after exposure.
CONCLUSION: This study demonstrates that brief exposure to contrast agents
injures EC and SMC, altering their structure and decreasing proliferation for up
to 7 days in vitro. This response is both dose and time dependent. EC are more
severely affected by ionic contrast, and SMC are more severely affected by
nonionic contrast. EC injury appears to be mediated by the osmolar effect of the
contrast, but the effects of contrast on SMC seem to be due to a different
mechanism.
PMID- 9652476
TI - Estrogen improves endothelial function.
AB - PURPOSE: To determine the effect of estrogen on endothelium-dependent relaxation
in the cutaneous microcirculation of women. METHODS: Three groups of women
participated in the study. Group 1 (n = 20) was premenopausal and had a mean age
of 39 years (range 24-50 years). Group 2 (n = 9) was postmenopausal and had a
mean age of 58 years (range 53-65 years). Group 3 (n = 11) was postmenopausal and
taking estrogen replacement therapy; the mean age was 53 years (range 43-58
years). Eleven women in group 1 underwent testing twice, once during menstruation
(mean serum estradiol level 73 +/- 30 pg/ml) and once during midcycle (mean serum
estradiol level 268 +/- 193 pg/ml; p = 0.003). Single-point laser Doppler
ultrasound and laser Doppler imaging with a scanner were used to measure
vasodilatation in the forearm skin in response to iontophoresis of 1%
acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium
independent smooth muscle relaxant). RESULTS: All three groups were matched for
body mass index and fasting glucose, total, high-density lipoprotein, and low
density lipoprotein cholesterol and triglyceride levels. All women had normal
blood pressure, and none smoked. Mean serum estradiol levels were 196 +/- 170
pg/ml (group 1), 35 +/- 12 pg/ml (group 2), and 107 +/- 78 pg/ml (group 3) (p =
0.004). Maximum microvascular vasodilatation (percentage increase over baseline)
in response to acetylcholine was reduced in group 2 (93% +/- 43%) compared with
group 1 (187% +/- 63%) and group 3 (142% +/- 56%) (p = 0.001). The response to
sodium nitroprusside also was diminished in group 2 (73% +/- 27%) compared with
group 1 (126% +/- 45%) and group 3 (100% +/- 32%) (p = 0.02). Within group 1 the
acetylcholine response was higher during the midcycle phase (186% +/- 31%)
compared with the menstrual phase (147% +/- 57%) (p < 0.05). The sodium
nitroprusside response also was higher during the midcycle phase (144% +/- 31%)
compared with the menstrual phase (94% +/- 41%) (p < 0.05) CONCLUSION: The
results indicate that estrogens might enhance endothelium-dependent and
endothelium-independent vasodilatation in the microcirculation of women.
PMID- 9652478
TI - Regarding "Limb asymmetry in titanium Greenfield filters: clinically
significant?".
PMID- 9652477
TI - Treatment of a postoperative cervical chylous lymphocele by percutaneous
sclerosing with povidone-iodine.
AB - The development of postoperative leaks of the thoracic duct after neck dissection
or vascular surgery of the subclavian and vertebral artery is a well-known but
rare complication. Usually, an injury of the duct manifests immediately after the
operation with chylous drainage. Presentation as a postoperative lymphocele is
rare. Operative treatment may be an option, but identification of the leak often
is impossible, resulting in a high rate of failure. Percutaneous catheter
drainage in combination with sclerosis with povidone-iodine has proved to be
highly effective in obliterating pelvic lymphoceles but has not been reported in
patients who have undergone vascular surgery in the neck. We present a case in
which a povidone-iodine solution was used successfully in percutaneous sclerosis
of a cervical lymphocele after transposition of the left subclavian artery to the
left common carotid artery.
PMID- 9652479
TI - Neck influences on the spatial properties of vestibulospinal reflexes in
decerebrate cats: role of the cerebellar anterior vermis.
AB - The vestibulospinal (VS) reflexes elicited by animal rotation modify the activity
of limb musculature, thus preserving balance and postural stability. We
investigated whether the orientation of these postural responses is strictly
dependent upon the direction of head displacement or else can be modified by
extralabyrinthine inputs to the goal of stabilizing body position. The
experiments were performed in decerebrate cats, in which the effects of static
body-to-head displacements were tested on the multiunit EMG responses of the
medial head of the triceps brachii to wobble of the whole animal at 0.15 Hz, 10
degrees, both in the clockwise (CW) and counterclockwise (CCW) direction. These
stimuli allowed us to determine the muscle response vector, whose orientation
component corresponds to the direction of head displacement giving rise to the
maximal EMG response. When the animal body was kept straight with respect to the
head, the triceps response vector was always oriented close to the transverse
axis, pointing to the side-down direction. Following 30 degrees of body-to-head
displacement around a vertical axis passing through the first-second cervical
joints, the response vectors of both the left and the right muscles shifted in
the same direction of body rotation, thus remaining approximately perpendicular
to the body axis. The change in muscle vector orientation corresponded on the
average to the angle of body-to-head displacement. Only slight changes in
amplitude of the muscle responses were observed. These findings imply that the
maximal activation of the triceps brachii always occurred for the same direction
of body displacement, irrespective of the pattern of discharge of vestibular
afferents, which is determined by the direction of head displacement. The
rotation of the triceps response vector induced by body-to-head displacement was
reduced or suppressed by inactivation of the ipsilateral cerebellar anterior
vermis, following local microinjection of the GABA(A) agonist muscimol. These
findings indicate that 1) the sensory input which results from changing the body
position with respect to the head, probably originating from neck receptors, is
able to modify the pattern of the VS reflexes, which appear to be organized in a
body-centered reference frame, and 2) the cerebellar vermis is required for the
proper execution of this sensorimotor transformation.
PMID- 9652480
TI - Post-rotatory nystagmus and turning sensations after active and passive turning.
AB - We measured post-rotatory nystagmus and sensations of body rotation in standing
subjects brought to rest in the dark after 3 minutes of each of the following
conditions: 1) passive turning about the mid-body axis, involving only vestibular
stimulation, 2) active turning about the mid-body axis, involving both vestibular
stimulation and motor-proprioceptive activity in the legs, and 3) stepping round
while remaining facing in the same direction on the center of a rotating platform
with the head held in a stationary holder (apparent turning), involving only
motor-proprioceptive activity. The same acceleration-velocity profile was used in
all conditions. Post-rotatory nystagmus (slow phase) occurred in the same
direction to passive body turning and was reduced in velocity after active body
turning. After apparent turning, nystagmus was in the opposite direction as
attempted body turning. Our theoretical analysis suggests that nystagmus after
active turning should conform to the mean of the responses after passive and
apparent turning rather than to their sum. The results conform more closely to
the mean than to the sum, but with greater weight given to vestibular inputs than
to motor-proprioceptive inputs. Post-rotatory sensations of self-rotation were in
the expected opposite direction after passive turning and were lower in magnitude
after active turning. After apparent turning, sensations of self-rotation were in
the same direction as those after attempted turning--an effect known as the
antisomatogyral illusion.
PMID- 9652481
TI - Spectral analysis of low-frequency, active-head vestibulo-ocular reflex
responses.
AB - Useful medical diagnostic information has been reported from low-frequency
rotational testing of the horizontal vestibulo-ocular reflex (VOR) of patients
with vestibular disorders. Servocontrolled rotating systems have been used as the
only practical method to generate stimuli over lower VOR frequency response
ranges, the decade from 0.01 to 0.1 Hz. Active head movements have been used for
testing the human VOR at higher frequencies, exceeding 0.5 Hz. We examined
whether active head movements could be used also to test the VORs of subjects
over lower frequency ranges, extending to 0.02 Hz. We used a swept-frequency,
active head movement protocol to generate a broad-band stimulus. Eye position was
recorded with electro-oculography. Head velocity was recorded with a rotational
sensor attached to a head band. Six individual test epochs from human subjects
were concatenated to form complex, periodic waveforms of head and eye velocity,
75 seconds in duration. Broad-band cross-spectral signal processing methods were
used to compute horizontal VOR system characteristics from these waveforms
extending from 0.02 to 2 Hz. The low-frequency VOR data appeared to originate
from amplitude modulation of high-frequency active movements, acting as carrier
signals. Control experiments and processing of simulated data from a known system
excluded the possibility of signal processing artifacts. Results from six healthy
subjects showed low-frequency gains and phase values in ranges similar to those
from published rotational chair studies of normal subjects. We conclude that it
is feasible to test the human VOR over extended low-frequency ranges using active
head movements because of amplitude modulation of the head and eye signals.
PMID- 9652482
TI - Why do benign paroxysmal positional vertigo episodes recover spontaneously?
AB - It is well known that most episodes of benign paroxysmal positional vertigo
(BPPV), even in untreated, recover spontaneously in 2 to 6 weeks. In the present
study, we put forward the hypothesis that this is mainly due to the fact that
endolymph, owing to its low calcium content (20 microM) is able to dissolve
otoconia. To support this, the fate of frog saccular otoconia immersed in normal
endolymph (Ca2+ content 20 microM) and in Ca2+-rich endolymphatic fluids (up to
500 microM) was studied by observing the crystals at regular intervals for 3
weeks. The results demonstrated that normal endolymph can dissolve otoconia very
rapidly (in about 20 hours). When the endolymphatic Ca2+ content was increased
(50 to 200 microM) otoconia dissolution time was slowed down (about 100 to 130
hours, respectively) and completely stopped when the endolymphatic Ca2+ content
was of 500 microM. The present results therefore suggest that the major process
involved in the spontaneous recovery of BPPV episodes is the capability of the
endolymph to dissolve dislodged otoconia.
PMID- 9652483
TI - Adaptation of the VOR in patients with low VOR gains.
AB - Six subjects with histories of vertigo and with vestibulo-ocular reflex (VOR)
gains less than 0.5 were tested in an adaptation protocol. After initial VOR
testing in the dark, the subjects had a computer-driven visual display system
placed on their heads. The system had the capability for variation of visual
image magnification. The magnification was set to be 5% greater than the
subject's average VOR gain. Subjects then performed active head movements as they
carried out a visual searching task looking for objects in a panoramic scene.
After 6 minutes with each image, the magnification was increased by 3 to 5%. The
process was repeated for a total of 5 images, for a total increase in
magnification of approximately 20% over 30 minutes. The VOR gain was measured
again. In 17 of 18 conditions tested, the VOR gain increased. The average
increase was 16%. Significant increases in VOR gain occurred at 0.32 and 0.64 Hz.
The VOR gain increase in these patients occurred in a visual environment that
lowered VOR gain in normal subjects. These results suggest that the VOR has an
adaptation mechanism tuned to correct for small changes in required gain. Further
research is necessary to determine if this method can result in persistent VOR
gain improvements and reduction in symptoms and disability in patients with
vestibular disorders.
PMID- 9652484
TI - Examination of two methods for statistical analysis of data with magnitude and
direction emphasizing vestibular research applications.
AB - When the dependent (or response) variable response variable in an experiment has
direction and magnitude, one approach that has been used for statistical analysis
involves splitting magnitude and direction and applying univariate statistical
techniques to the components. However, such treatment of quantities with
direction and magnitude is not justifiable mathematically and can lead to
incorrect conclusions about relationships among variables and, as a result, to
flawed interpretations. This note discusses a problem with that practice and
recommends mathematically correct procedures to be used with dependent variables
that have direction and magnitude for 1) computation of mean values, 2)
statistical contrasts of and confidence intervals for means, and 3) correlation
methods.
PMID- 9652485
TI - Magnetoencephalography and magnetic source imaging.
AB - Current brain imaging techniques, such as computed tomography (CT) and magnetic
resonance imaging (MRI), provide noninvasive, high-resolution images that depict
fine anatomic structure and delineate pathology by control of image contrast and
sensitivity to the physicochemical microenvironment. These methods, although
invaluable for the identification, characterization, and localization of lesions,
do not provide any assessment of the functional viability of brain tissues, nor
of the spatial organization of sensory, motor, and cognitive systems. However,
such additional functional information is of great significance to the clinician
in the determination of treatment strategies and patient management.
PMID- 9652486
TI - Hand preference and magnetic resonance imaging asymmetries of the central sulcus.
AB - Hand preference is perhaps the most evident behavioral asymmetry observed in
humans. Anatomic brain asymmetries that may be associated with hand preference
have not been extensively studied, and no clear relationship between asymmetries
of the motor system and hand preference have been established. Therefore, using
volumetric magnetic resonance imaging methodologies, the surface area of the hand
representation was measured along the length of the central sulcus in 15
consistent right- and 15 left-handers matched for age and gender. There was a
significant leftward asymmetry of the motor hand area of the precentral gyrus in
the right-handers, but no directional asymmetry was found in the left-handers.
When asymmetry quotients were computed to determine the distribution of
interhemispheric asymmetries, the left motor bank was greater than the right
motor bank in 9 of 15 right-handers, the right motor bank was greater than the
left motor bank in 3 of 15 right-handers, and the motor banks were equal in 3 of
15 right-handers. In contrast, among left-handers, the left motor bank was
greater than the right motor bank in 5 of 15, the right motor bank was greater
than the left motor bank in 5 of 15, and the motor banks were equal in 5 of 15.
Although no direct measure of motor dexterity and skill was performed, these data
suggest that anatomic asymmetries of the motor hand area may be related to hand
preference because of the differences in right-handers and left-handers.
Furthermore, the predominant leftward asymmetry in right-handers and the random
distribution of asymmetries in the left-handers support Annett's right-shift
theory. It is unclear, however, whether these asymmetries are the result of
preferential hand use or are a reflection of a biologic preference to use one
limb over the other.
PMID- 9652487
TI - The effects of rotation on spatial attention.
AB - Unilateral spatial neglect can be reduced by cold water caloric stimulation of
the contralesional ear. Three hypotheses may account for this response. Caloric
stimulation may increase the arousal of the damaged hypoaroused hemisphere.
Moving stimuli to ipsilesional space improves the performance of patients with
neglect. Caloric stimulation may move viewer-centered spatial maps in an
ipsilesional direction. Unilateral neglect may be related to a spatial
attentional bias. Vestibular stimulation may temporarily influence this bias. To
learn if vestibular stimulation may induce an attentional spatial bias, the
authors studied eight normal subjects by having these subjects attempt to bisect
lines before and during vestibular stimulation. If caloric stimulation alters
neglect because it changes the attentional spatial bias, the authors should be
able to induce neglect in normal subjects by pertubating the vestibular system.
Vestibular stimulation was induced by spinning a chair and then abruptly stopping
the spinning chair. The authors found that after normal subjects were rotated to
the left, they misbisected lines to the left but did not misbisect lines after
they were rotated to the right. Although these results support the postulate that
vestibular stimulation can induce an attentional spatial bias, the authors'
results also suggest that there are intrinsic attentional asymmetries.
PMID- 9652488
TI - The evolution of alexia and simultanagnosia in posterior cortical atrophy.
AB - Early alexia and higher visual impairments characterize Posterior cortical
atrophy (PCA), a progressive dementing syndrome most often caused by Alzheimer
disease. Posterior cortical atrophy is rare, and the nature of the visual
impairments in PCA are unclear. The authors observed two patients who had an
insidiously progressive reading difficulty characterized by letter-by-letter
reading and otherwise intact cognitive functions. Over time, these patients
developed "ventral simultanagnosia" with preserved detection of multiple stimuli
but inability to interpret whole scenes. Subsequently, they progressed to Balint
syndrome with "dorsal simultanagnosia," optic ataxia, and oculomotor apraxia.
Structural imaging was normal, but functional imaging revealed posterior cortical
dysfunction. On a letter reading task, both patients had a word superiority
effect, and on a whole word reading task, they could not read most words with
missing or crosshatched letters. An inability to assess whole scenes progressed
to an inability to detect more than one stimulus in an array. These findings
suggest an evolution of PCA with progressive difficulty in visual integration
beginning with letters, progressing to whole scenes, and culminating in Balint
syndrome. These changes may reflect an extension of the pathophysiology of PCA
from the extrastriate visual cortex to its occipitotemporal and occipitoparietal
connections.
PMID- 9652489
TI - Functional imaging: heterogeneity in task strategy and functional anatomy and the
case for individual analysis.
AB - To learn more about the functional anatomy of language, the authors used
[99mTc]HMPAO single photon emission computed tomography (SPECT) functional
imaging to study nonword rhyming, lexical-semantics and syntax. The authors did
not find any task-related differences in cerebral blood flow using region-by
region analysis of variance. This led them to examine individual subject's task
related patterns of cerebral blood flow. This analysis revealed regions of
interest with little or no change but also regions with changes as great as 30%.
There was marked subject-to-subject variability in the pattern of blood flow,
which precluded statistically significant results using analysis of variance. An
alternative analytic strategy based on numbers of subjects exceeding a minimum
threshold task-related change in cerebral blood flow was tested and shows promise
in identifying commonalities and differences in individual task-related blood
flow patterns. The authors conclude that the complex and difficult to interpret
pattern of blood flow changes observed in this study reflect in considerable part
the combined effects of variability in task strategy, owing in part to
insufficiently constrained task performance, and variability in functional
anatomy. The authors also tested the differences in results achieved with simple
normalization and analysis of covariance approaches and found them to be
insignificant.
PMID- 9652490
TI - Patterns and associates of hyperphagia in patients with dementia.
AB - This study examined patterns and associates of excessive eating (hyperphagia) in
a community-based registry of patients with dementia. From patients enrolled in
the Mayo Clinic Alzheimer's Disease Patient Registry (n = 439), 39 were
identified with excessive eating reported on the Behavior Symptom Checklist at
some time during their illness. They were matched for age, gender, duration of
disease, and Global Deterioration Scale (GDS) score to "normal eaters."
Annualized weight change was determined based on weight from the 6 months before
the evaluation to weight 6 months after the evaluation. Annualized weight change
scores were not significantly different between excessive eaters and normal
eaters nor between wanderers and nonwanderers. In cross-sectional analysis,
univariate modeling suggested age at onset, GDS, and Mini-Mental State
Examination score to be significant predictors of excessive eating. Using
multivariate logistic model with backward elimination, only age of onset and GDS
were retained as associates of excess eating. Rater type also emerged as a
significant predictor for excessive eating with family raters reporting this
behavior in 16% of patients compared to 5% for other raters. In chi-square
analyses excessive eating was associated with greater frequency of wandering,
unpredictable behavior, inappropriate dressing, inappropriate bodily concerns,
and threatening self-harm. Associates of excess eating were subsequently examined
separately in wandering and nonwandering excessive eaters. Logistic modeling
suggested that among nonwanderers, patients who were younger but more severely
demented were likely to have reported excessive eating. These results suggest
hyperphagia to be present in approximately 10% of a community-based cohort of
patients with dementia and associated with increasing functional decline.
Excessive eating does not appear to arise from memory dysfunction, but for
wanderers may result from needing increased caloric intake because of increased
activity levels. Thus, for wandering excessive eaters, it may be appropriate to
endure the eating to ensure appropriate caloric intake. Nonwandering excessive
eaters were younger, had greater dementia severity, and had more unpredictable
behavior. They may have dementia with prominent frontal lobe involvement and may
respond to any food stimulus respective of hunger. Restricting food exposure may
be an effective management intervention for them.
PMID- 9652491
TI - Olfactory reference syndrome in a patient with partial epilepsy.
AB - A 49-year-old man with right temporal lobe epilepsy developed the chronic
delusion that his body emitted a foul odor (olfactory reference syndrome). Before
the delusional symptoms, he had partial seizures with unpleasant olfactory
hallucinations. Subsequently ictal olfactory symptoms abated but a disabling
delusional syndrome developed. The only prior case of the olfactory reference
syndrome in a patient with epilepsy had a right frontal lesion. The case further
supports the association of right hemisphere lesions and delusional disorders.
PMID- 9652492
TI - Remote memory after basal forebrain damage.
PMID- 9652493
TI - Introduction. Monothematic courses.
PMID- 9652494
TI - Clinical manifestations of seronegative spondylarthropathies.
AB - Seronegative spondylarthropathies include ankylosing spondylitis, Reiter's
syndrome and reactive arthritis, psoriatic arthritis, arthritis associated with
ulcerative colitis and Crohn's disease, plus other forms which do not meet the
criteria for definite categories and are called undifferentiated. Recently two
sets of classification criteria have been proposed for the entire group including
undifferentiated forms: the European Spondylarthropathy Study Group and the Amor
criteria. The prevalence of spondylarthropathies is directly correlated with the
prevalence of the HLA-B27 antigen in the population. The highest prevalence of
ankylosing spondylitis (4.5%) has been found in Canadian Haida Indians, where 50%
of the population is B27 positive. Among Europeans the frequency of the B27
antigen in the general population ranges from 3 to 13% and the prevalence of
ankylosing spondylitis is estimated to be 0.1-0.23%. Seronegative
spondylarthropathies have common clinical and radiologic manifestations:
inflammatory spinal pain, sacroiliitis, chest wall pain, peripheral arthritis,
peripheral enthesitis, dactylitis, lesions of the lung apices, conjunctivitis,
uveitis and aortic incompetence together with conduction disturbances. All of
these may also occur in isolation.
PMID- 9652495
TI - Diffuse idiopathic skeletal hyperostosis.
AB - OBJECTIVE: To describe the axial and appendicular skeleton findings of diffuse
idiopathic skeletal hyperostosis. To analyze the role of conventional
radiography, computed tomography (CT) and magnetic resonance imaging (MRI) in the
diagnosis of this condition. To discuss the differential diagnosis and diagnostic
pitfalls of this disease. MATERIAL AND METHODS: The involvement of vertebral and
extravertebral sites including the pelvis, calcaneum, ulnar olecranon, and
patella is frequently found in the literature. The lesions described are the
anterior and lateral ossification of the spine, hyperostosis at sites of tendon
and ligament insertion, ligamentous ossification, and periarticular osteophytes.
The criteria for the diagnosis of diffuse idiopathic skeletal hyperostosis
involving the spine are: flowing ossification along the anterior and
anterolateral aspects of at least four contiguous vertebrae, preserved
intervertebral disc height, no bony ankylosis of the posterior spinal facet
joints, and finally no erosion, sclerosis or bony ankylosis of the sacroiliac
joints. RESULTS: The disease has about the same frequency in men (65%) and women
(35%); it is most common in the thoracic spine and occurs less frequently in the
lumbar and cervical spine. The disease most commonly presents in the sixth and
seventh decades of life and its estimated frequency in the elderly is 5-15%.
Signs and symptoms include stiffness and pain in the back, dysphagia due to
direct esophageal compression/distorsion, pain related to associated tendinitis,
myelopathy related to core compression associated to the ossification of the
posterior longitudinal ligament, and pain related to vertebral complications-
e.g. fracture/subluxation. CONCLUSION: While conventional radiography clearly
confirms the diagnosis of diffuse idiopathic skeletal hyperostosis, CT and MRI
better detect associated findings (e.g. ossification of the posterior
longitudinal ligament) and complications (e.g. spinal cord compressive
myelomalacia).
PMID- 9652496
TI - Seronegative spondylarthropathies: imaging of spondylitis, enthesitis and
dactylitis.
AB - Sacroiliitis is an indispensable condition for the diagnosis of ankylosing
spondylitis according to the present criteria and is usually diagnosed on
standard anteroposterior radiographs of the pelvis. In cases with suspicious
abnormalities (grade 1 of the New York criteria) CT permits the diagnosis since
it shows a higher degree of sacroiliitis. MRI is superior to CT in the early
diagnosis as it can detect the cartilage abnormalities which precede bony
changes. 'Romanus lesions' with 'shiny corners', 'squaring' of the vertebral
bodies, syndesmophytes, spondylodiscitis and osteoporosis are the radiological
findings of ankylosing spondylitis. The nonmarginal, asymmetric, coarse and broad
syndesmophytes of psoriatic spondylitis and spondylitis associated with Reiter's
syndrome resemble the flowing bone outgrowths of diffuse idiopathic skeletal
hyperostosis (DISH). The ossification of the posterior longitudinal ligament and
of the flavum ligament are rare manifestations of ankylosing spondylitis.
Peripheral extra-articular enthesitis is a clinical hallmark of seronegative
spondylarthropathies. Plain film radiography shows erosions and spurs but only in
advanced phases. US shows the swelling of the entheses and the peritendinous soft
tissues and the distension of adjacent bursae by fluid collection. MRI shows the
inflammation of the bone adjacent to the insertion as well as the soft tissue
changes. Dactylitis is another typical manifestation of seronegative
spondylarthropathies. In the past it was thought to be due to concomitant
tenosynovitis and arthritis. Recently, however, we have demonstrated with US and
MRI that the 'sausage-like' appearance is due to the flexor tenosynovitis and
that joint capsule distension is not indispensable.
PMID- 9652497
TI - The clinical features of rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
progressive damage of synovial-lined joints and variable extra-articular
manifestations. Tendon and bursal involvement are frequent and often clinically
dominant in early disease. RA can affect any joint, but it is usually found in
metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints, as
well as in the wrists and knee. Articular and periarticular manifestations
include joint swelling and tenderness to palpation, with morning stiffness and
severe motion impairment in the involved joints. The clinical presentation of RA
varies, but an insidious onset of pain with symmetric swelling of small joints is
the most frequent finding. RA onset is acute or subacute in about 25% of
patients, but its patterns of presentation also include palindromic onset,
monoarticular presentation (both slow and acute forms), extra-articular synovitis
(tenosynovitis, bursitis), polymyalgic-like onset, and general symptoms (malaise,
fatigue, weight loss, fever). The palindromic onset is characterized by recurrent
episodes of oligoarthritis with no residual radiologic damage, while the
polymyalgic-like onset may be clinically indistinguishable from polymyalgia
rheumatica in elderly subjects. RA is characteristically a symmetric erosive
disease. Although any joint, including the cricoarytenoid joint, can be affected,
the distal interphalangeal, the sacroiliac, and the lumbar spine joints are
rarely involved. The clinical features of synovitis are particularly apparent in
the morning. Morning stiffness in and around the joints, lasting at least 1 h
before maximal improvement is a typical sign of RA. It is a subjective sign and
the patient needs to be carefully informed as to the difference between pain and
stiffness. Morning stiffness duration is related to disease activity. Hand
involvement is the typical early manifestation of rheumatoid arthritis. Synovitis
involving the metacarpophalangeal, proximal interphalangeal and wrist joints
causes a characteristic tender swelling on palpation with early severe motion
impairment and no radiologic evidence of bone damage. Fatigue, feveret, weight
loss, and malaise are frequent clinical signs which can be associated with
variable manifestations of extra-articular involvement such as rheumatoid
nodules, vasculitis, hematologic abnormalities, Felty's syndrome, and visceral
involvement. Although there is no laboratory test to exclude or prove the
diagnosis of rheumatoid arthritis, several laboratory abnormalities can be
detected. Abnormal values of the tests for evaluation of systemic inflammation
are the most typical humoral features of RA. These include: erythrocyte
sedimentation rate, acute phase proteins and plasma viscosity. Erythrocyte
sedimentation rate and C-reactive protein provide the best information about the
acute phase response. The C-reactive protein is strictly correlated with clinical
assessment and radiographic changes. Plain film radiography is the standard
investigation to assess the extent of anatomic changes in rheumatoid arthritis
patients. The radiographic features of the hand joints in early disease are
characterized by soft tissue swelling and mild juxtaarticular osteoporosis. In
the the past 10 years, ultrasonography has gained acceptance for studying joint,
tendon and bursal involvement in RA. It may improve the early clinical assessment
and the follow-up of these patients, showing such details as synovial thickening
even within finger joints. Other imaging techniques, such as magnetic resonance,
computed tomography and scintigraphy may provide useful information about both
the features and the extent for anatomic damage in selected rheumatoid arthritis
patients. The natural history of the disease is poorly defined; its clinical
course is fluctuating and the prognosis unpredictable. RA is an epidemiologically
relevant cause of disability. An adequate early treatment of RA may alter the
diseas
PMID- 9652498
TI - Rheumatoid arthritis: follow-up and response to treatment.
AB - OBJECTIVE: To assess the role of diagnostic imaging techniques in the
identification and follow-up of the anatomical damage induced by the chronic
inflammatory process of rheumatoid arthritis (RA) not only to study the natural
history of the disease but also and especially to assess the long-term response
to disease-modifying anti-rheumatic drugs (DMARD). MATERIALS AND METHODS: The
relative literature data were reviewed and compared with our personal experience
with different imaging modalities such as conventional radiography (CR),
ultrasound (US) and magnetic resonance imaging (MRI). RESULTS: Several radiologic
techniques have been used over the years to study articular damage in RA: they
describe and quantify the articular damage (semi-quantitative analysis) based on
a series of parameters and elementary anatomical lesions which are given a rising
score. For its sensitivity in detecting early disease signs and the possibility
to express anatomical damage progression quantitatively, Sharp's index is
considered the best tool for evaluating RA patients. The close correlation
between clinical parameters and the radiologic scores obtained regardless of the
method applied led to a new concept of anatomical damage related to the
'radiologic progression of the disease' which is a more precise measure of RA
severity than the single isolated radiograph. The progression of radiologic
damage in rheumatoid arthritis is expressed as the number or proportion of new
eroded joints/year: independent of the index adopted and the terms used to
express progression, severe radiologic damage occurs in the early disease stage,
involving approximately 2% of the joints within about 1 year, and 13% within 2
years, with an estimated average annual progression of 1.3%. Radiologic
techniques evaluate the anatomical damage in the course of RA only with reference
to the osseous component of the joint and therefore apply to a disease stage that
is largely irreversible. MRI and US detect the soft-tissue damage occurring in
the earlier phases and are more likely to respond to early treatment. The former
technique appears to be useful to detect soft-tissue damage like synovial pannus,
intra- and periarticular and peritendinous effusion, capsuloligamentous articular
and tendon changes. Its high sensitivity for minimal bone erosions and
chondromalacia has been demonstrated. US allows to demonstrate a wide range of
soft-tissue changes of the hand and wrist. Joint-cavity widening, loss of
cartilage definition, bone erosions, widening of flexor tendon sheath and tendon
structure are also well depicted on ultrasound images. CONCLUSIONS: CR is the
central tool in the diagnosis, staging and follow-up of RA patients and in
general in the assessment of treatment efficacy; MRI and US are complementary
tools.
PMID- 9652499
TI - Rheumatoid arthritis: sequences.
AB - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disorder of unknown
etiology characterized by symmetric, erosive synovitis and sometimes multisystem
involvement. It affects 1% of the adult population and exhibits a chronic
fluctuating course which may result in progressive joint destruction, deformity,
disability and premature death. We review the literature data relative to the
peculiar pathologic features of the disease shown by diagnostic imaging
techniques. METHODS: All our patients were classified according to the diagnostic
criteria of the American Rheumatism Association (1987). Plain radiography remains
the diagnostic technique of choice, but ultrasound (US), computed tomography (CT)
and magnetic resonance imaging (MRI) are also used. RESULTS: Clinically articular
involvement presents as pain, swelling, stiffness and motion impairment. The
patients with positive rheumatoid factor are > 70% likely to develop joint damage
or erosions within 2 years of disease onset. Any joint can be involved, but the
proximal interphalangeal and metacarpophalangeal joints of the hand and the wrist
are preferential sites, as well as the metatarsophalangeal joint of the foot, the
knee and the joints of the shoulder, the ankle and the hip. Symmetry is the
hallmark of joint involvement. The synovium of bursae and tendon sheaths is also
affected. Soft tissue (subcutaneous nodules), muscles (weakness and atrophy) and
vessels (vasculitis) may also be involved. Systemic involvement may result in
Felty's syndrome, metabolic bone disorders (i.e. osteoporosis), Sjogren syndrome
and pleuropulmonary abnormalities (pleural effusion, fibrosing alveolitis,
constrictive bronchiolitis). The earliest abnormalities consist in synovial
proliferation, soft tissue swelling, and osteoporosis. At a slightly later stage,
the inflamed synovial tissue ('pannus') extends across the cartilage surface,
leading to chondral erosions and small bone erosions at the joint margin (bare
areas). Marginal and central erosions follow in advanced stages and finally
fibrous ankylosis, joint deformities (subluxations and dislocations), fractures
and fragmentations are typical findings of more advanced RA. CONCLUSION: RA is a
frequent joint disorder with a characteristic radiographic picture. Joint
involvement patterns are sufficiently common to permit accurate diagnosis,
especially when fusiform soft tissue swelling, regional osteoporosis, marginal
and central erosions and diffuse loss of interosseous space are present.
Conventional radiography remains the standard imaging technique for joint studies
in the patients with suspected RA. US is recommended to diagnose soft tissue
involvement (joint effusion). CT is very useful for showing abnormal processes in
complex joints (sacroiliac and temporomandibular joints and craniocervical
junction) which are difficult to depict completely with conventional radiography.
Magnetic resonance applications include the assessment of disease activity: in
particular, this technique may be the only tool differentiating synovial fluid
and inflammatory pannus.
PMID- 9652500
TI - Joint impingement syndrome: clinical features.
AB - Joint impingement is a painful syndrome caused by the friction of joint tissues,
which is both the cause and the effect of altered joint biomechanics. From the
anatomical and clinical viewpoints, these syndromes are classified as bone
impingement, soft tissue impingement and entrapment neuropathy, depending on what
joint portion impinges on the others. We considered the most important
impingement syndromes of the upper and the lower limbs from the clinical
viewpoint. As for the upper limb, supraspinatus impingement is a frequent cause
of shoulder pain in both athletes and the normal population; the painful
subacromial arch is a typical sign of the rotator cuff impingement syndrome and
of outlet and non-outlet impingement as well. As for the elbow, we considered
both medial and lateral impingement. The carpal tunnel syndrome is the most
common peripheral entrapment neuropathy of the upper limb; it is caused by
compression of the median nerve at the wrist. We considered the main causes of
carpal tunnel narrowing and the relative clinical findings. As for the lower
limb, we considered the iliotibial band friction syndrome, which is the most
common overuse syndrome of the knee and the ankle impingement syndrome. The
latter includes anterolateral impingement (with chronic anterolateral and lateral
pain and ankle instability), sinus tarsi impingement, anterior impingement (with
pain during foot dorsiflection and posterior impingement. The tarsal tunnel
syndrome is the most important ankle entrapment neuropathy causing burn pain and
paresthesias in the toes and sole of the foot.
PMID- 9652501
TI - Shoulder impingement syndromes.
AB - OBJECTIVE: Not all shoulder pain conditions are a consequence of rotator cuff
injuries secondary to anterior subacromial impingement. Additional causative
forms have been identified and classified as posterosuperior glenoid rim,
subcoracoid and suprascapular nerve (at spinoglenoid notch) impingement
syndromes. MATERIAL AND METHODS: We reviewed 206 consecutive magnetic resonance
examinations carried out with conventional T1- and T2-weighted spin-echo and
gradient-echo sequences in patients complaining of shoulder pain. Adjunctive
sequences were acquired with the involved arm positioned in abduction and
external rotation. RESULTS: Anterior subacromial impingement is only one of the
possible causes of shoulder disorders. Posterosuperior glenoid rim impingement is
the most frequent cause of shoulder pain in young throwers. Subcoracoid and
spinoglenoid notch suprascapular nerve impingement are additional forms that must
be considered in the differential diagnosis because of their frequent occurrence
in routine clinical practice. CONCLUSION: Magnetic resonance imaging is the most
useful diagnostic modality for shoulder disorders.
PMID- 9652502
TI - Sports injuries in the pelvis and hip: diagnostic imaging.
AB - We discuss the role of imaging techniques in examining the athletes with sports
injuries involving the pelvis and the hip. Pelvis and hip pain is of difficult
clinical clarification because of the various athletic injuries which may affect
the bone or soft tissues at different anatomic sites. Moreover, the symptoms of
pelvis and hip injuries are similar in most cases and they are often diffuse and
atypical. Diagnostic imaging can play an essential role because treatment success
depends on a correct diagnosis and these techniques can actually differentiate
the most frequent causes of pelvis and hip sports injuries such as groin strain,
osteitis pubis, ischial intersection syndrome, snapping hip, stress fractures,
hernias and avulsion fractures. Finally, we discuss the role of magnetic
resonance imaging in detecting the causes of hip pain other than sports injuries,
such as avascular necrosis, reflex sympathetic dystrophy syndrome, herniation
pit, acetabular labrum injuries. To conclude, diagnostic imaging techniques
currently permit the direct and noninvasive depiction of pelvis and hip
conditions. Particularly, magnetic resonance imaging is very helpful in detecting
injury site, extent and characteristics; it can also predict the time period an
athlete will be disabled and help define the best treatment planning.
PMID- 9652503
TI - Knee impingement syndromes.
AB - INTRODUCTION: The so-called knee impingement syndromes are very frequently
reported in both professional and amateur sportsmen. PURPOSE: The objective of
our study was to classify the most frequent knee changes responsible for such
syndromes considering both pathology and diagnostic work-up. MATERIAL AND
METHODS: Our patients complained of aspecific symptoms related to articular
meniscal, ligament or cartilage, conditions. The site of pain was periarticular
and there was no apparent sign of acute traumatic events. All individuals, aged
16-55, practised sports at different levels and women were the majority of the
sample. The study was carried out from 1995 to 1997 and all the medical records
presented in occasion of the sports-medicine check-up were reviewed. RESULTS: The
sites of symptom onset were divided into medial, lateral, anterior and posterior.
For each of them the most frequent conditions which could be defined as
impingement syndromes, were defined paying particular attention to the possible
methods of diagnosis useful to classify the disorder. As for anterior syndromes,
patellofemoral disorders were the most frequent findings. They were associated
with either incorrect torsion movements of the lower limbs or local dysplasia.
Alterations in the single skeletal and cartilage structures were reported. Always
referring to anterior syndromes, Hoffa's fat pad imflammation and the jumper's
knee were a less frequent finding. As for posterior impingement syndromes, the
most frequent abnormalities involved the insertional tract of the midcalf muscle
associated with bursa reaction and insertional popliteus hypertrophy. As for
medial syndromes, the most frequent abnormality involved the parapatellar
synovial fold whose symptoms can be often mistaken for a meniscal injury. Less
frequent is the involvement of the 'pes anserinus' tendinitis and the insertional
enthesopathy of the semimembranosus muscle. As for lateral syndromes, the
phlogistic involvement of the distal insertional tract of the broad fascia tensor
tendon with bursa reaction is very frequently reported, while the inflammation of
the popliteal tendon and of the femoral bicipital tendon is less common.
CONCLUSIONS: Although less frequent than meniscal and ligament injuries,
impingement syndromes must be taken into due consideration when looking for knee
disorders resorting to different diagnosis methods. Diagnostic imaging is very
useful in this regard as it allows a proper and correct diagnosis procedure for
any single condition.
PMID- 9652504
TI - Ankle impingement syndromes.
AB - The ankle impingement syndrome is a frequent condition in both athletes and the
normal population. We investigated this painful syndrome from both a clinical and
a diagnostic viewpoint. Depending on what ankle tissue impinges on the other, it
is possible to distinguish bone impingement, soft tissue impingement and
peripheral nerve entrapment. For each of these pathologic conditions we
investigated the diagnostic role of conventional radiography, Computed Tomography
and Magnetic Resonance Imaging. The evidence of osteophytes, exostosis and
presence of the os trigonum on plain films make clinical diagnosis easy in both
anterior and posterior bone impingement. CT can provide useful information about
the component of the posterior ankle. MRI always adds important information about
chondral or subchondral bone injuries, synovial reaction and adjacent soft tissue
involvement. The anterolateral impingement syndrome is caused by repeated
injuries in plantar flexion and ankle intrarotation. MRI well detects the
meniscoid injury thanks to high contrast sequences; it can also distinguish this
syndrome from painful chondral and/or bony lesions at this level. MRI is also the
method of choice to study sinus tarsi impingement, especially thanks to fat
suppression sequences which increase MR diagnostic capabilities in this important
anatomic area. Deep peroneal nerve entrapment, the medial plantar nerve
entrapment syndrome and the tarsal tunnel syndrome are the most important
entrapment neuropathies of the ankle. US and MRI are very useful to study the
tendon and soft tissue abnormalities causing the anterior tarsal tunnel syndrome.
CT and particularly MRI can easily detect many pathologic conditions causing the
medial plantar nerve entrapment and the tarsal tunnel syndromes.
PMID- 9652505
TI - Classification of bone tumors.
AB - The classification of bone tumors relies on the cytologic features and products
of tumor cells. This classification is reproducible and accepted by pathologists,
oncologic surgeons and oncologists. Chondrogenic tumors are the second largest
group of bone tumors. Their histologic pattern suggests a relationship to hyaline
cartilage. Exostoses, or osteochondromas, represent about 1/3 of chondrogenic
lesions. Chondromas are hyaline cartilage tumors which can be found centrally or
subperiosteally; they may contain some calcifications and/or ossifications.
Chondroblastomas are tumors whose cells produce, at least focally, a matrix
similar to hyaline cartilage. Histology of chondromyxoid fibromas shows large or
small areas where proliferating cells produce a matrix resembling the hyaline
cartilage. Chondosarcomas are tumors whose malignant cells produce a
cartilaginous matrix. Most of them occur in previously normal bones; they are
classified as conventional or primary chondrosarcomas. Secondary chondrosarcomas
result from the malignant transformation of a benign cartilaginous lesion less
commonly enchondromas and most commonly osteocartilaginous exostoses, or
osteochondromas. Less common variants include dedifferentiated, mesenchymal and
clear cell chondrosarcomas. Osteogenic tumors are the third largest group of bone
tumors, with osteosarcomas being the most frequent type. The most important
criterion for a tumor to be considered an osteosarcoma is that the malignant
tumor cells must produce a recognizable osteoid matrix, at least focally.
Osteosarcomas are divided into three groups: osteoblastic, chondroblastic and
fibroblastic, according to the dominant histologic feature. Osteosarcomas can be
multifocal, synchronous or metachronous; they are also classified by the
histologic grade of malignancy. Pathologically low grade lesions, which are
clinically indolent, are generally known as low grade central and parosteal
osteosarcomas.
PMID- 9652506
TI - The current role of radiography in the assessment of skeletal tumors and tumor
like lesions.
AB - Radiography offers more information than any other imaging modality in the study
of bone lesions and remains the cornerstone for the differential diagnosis of
skeletal tumors and tumor-like lesions thanks to its higher specificity in
detecting tumor morphologic hallmarks. the radiographic features that help the
radiologist make the diagnosis of a bone tumor or tumor-like lesion, or at least
narrow the diagnostic possibilities, include patterns of bone destruction
(geographic, moth-eaten and permeated), lesion margins (from sclerotic rim to ill
defined margin), internal characteristics of the lesion (non-matrix producing
tumors, non-mineralized matrix producing tumors, mineralized matrix producing
tumors), type of host bone response (medullary or periosteal), location (femur,
tibia, humerus, etc.), site (metaphysis, diaphysis or epiphysis), and position
(central, eccentric or periosteal) of the lesion in the skeletal system and in
the individual bone, soft tissue involvement, and single or multiple lesion
nature. Patterns of bone destruction, margins, and reactive changes in the host
bone clearly depict the growth rate of a bone lesion, that is its biologic
activity; the matrix of the lesion, as well as lesion location, site and position
may allow a specific diagnosis. This general information coupled with clinical
information helps define whether the lesion is neoplastic or non-neoplastic,
benign or malignant, primary or metastatic, and will help further direct the
subsequent work-up. CT may be indicated for the optimal assessment of tumor
matrix especially in complex anatomical sites, such as the spine, pelvis and
hindfoot. The main role of MRI lies in local tumor staging, especially for
planning limb-salving resections. Biopsy is the definitive diagnostic procedure
and should be carried out only after the appropriate diagnostic and staging
tests. Whenever a bone lesion is suspected, clinical-radiologic pathologic
correlation is essential to make a more accurate diagnosis and to improve patient
care.
PMID- 9652507
TI - Diagnostic imaging of malignant cartilage tumors.
AB - We compared the diagnostic capabilities of CT and MRI in the study of malignant
cartilage tumors. Information about the characterization and the intra
/extraosseous spread of these lesions is of primary importance in the
preoperative planning. Besides peripheral chondrosarcomas, arising from an
osteochondroma and central chondrosarcomas, which are the most common malignant
cartilaginous tumors, we also considered secondary, periosteal, dedifferentiated,
clear cells and mesenchymal chondrosarcomas. Our study was performed using a
standard MRI and CT protocol; in some cases, the examination was completed by the
intravenous administration of a contrast agent. High contrast T2-weighted GE
images can perfectly depict and differentiate the cartilage cap of an
osteochondroma from the adjacent soft tissues. Evaluation of the growth of
exostosis and of the thickness of its cap is essential in the assessement of
malignant transformation. Both CT and MRI provide important information about
peculiar aspects of the cartilaginous matrix such as the shape of calcifications
ossifications and lobulated growth, septa, septal enchancement and necrotic
intratumoral areas, furthermore, CT perfectly shows the patterns of bone
destruction. MRI should be considered as the most reliable imaging technique for
the locoregional staging of malignant bone tumors thanks to its spatial and
contrast resolution. CT plays a major role in the characterization of most bone
tumors, especially those with a cartilaginous matrix.
PMID- 9652509
TI - Malignant tumors of the osteogenic matrix.
AB - This article focuses on major clinical and imaging features that are of practical
interest in the diagnosis and management of osteosarcoma, a malignant tumor
arising from the osteogenic matrix. The current histologic classification of this
tumor is also reported. Different types of osteosarcoma are described, each of
them with a definite clinical and radiographic pattern. Conventional radiography
is the keystone to diagnosis because it allows analysis of the patterns relevant
to the different lesions (location, site, bone destruction, periostal reaction,
soft tissue masses). The most common type of osteosarcoma is defined classic or
conventional high grade (75%) and it typically involves the medullary cavity.
Radiographically, it may be predominantly osteosclerotic or osteolytic, but more
frequently it has a mixed (osteoslerotic/osteolytic) pattern. The teleangiectatic
osteosarcoma is an aggressive form (5%) characterized by marked vascularization
with large blood-filled cystic cavities; its typical radiographic pattern is
purely osteolytic. Juxtacortical osteosarcoma (8-10%) indicates a group of
osteosarcomas apparently arising on bone surface. The most common type is
parosteal osteosarcoma which affects older subjects and has a better prognosis
than the classic type. Radiography shows a heavily ossified mass with a broad
base attached to the underlying cortex. CT and MRI are useful in the differential
diagnosis of osteosarcoma and myositis ossificans or osteocondroma. Rare types of
osteosarcoma include the periosteal and high-grade surface variants, as well as
secondary and multifocal osteosarcoma (osteosarcomatosis). CT and MRI are the
imaging procedures of choice in locoregional staging (intraosseous and
extraosseous spread, skip metastases, growth plate and articular involvement). CT
of the chest is a useful tool for detecting lung metastases. Also MRI has a role
in monitoring the response to chemotherapy and in detecting recurrence. It
permits a more accurate study of the tumor volume than other imaging techniques
and clinical examination. MRI becomes even more useful when paramagnetic contrast
agents are administered because dynamic MRI with contrast enhancement help
differentiate postchemotherapy changes from viable tumor--the latter enhancing
rapidly and the former slowly. Thus, dynamic MRI allows a precise mapping of any
residual tumor activity.
PMID- 9652508
TI - Skeletal benign bone-forming lesions.
AB - The imaging features of benign osseous lesions of the bone are often
characteristic and suggestive of a specific diagnosis. This is particularly true
for skeletal benign bone-forming lesions such as enostosis, osteoma, osteoid
osteoma and osteoblastoma. Enostosis or bone island is an incidental finding in
the axial skeleton (pelvis, spine, ribs) of asymptomatic patients; it appears as
a small (0.2-2 cm) round to oval sclerotic area with irregular, radiating
('thorny') spicules peripherally. Osteoma is a benign slow-growth tumor and
usually an incidental finding in cranial sinuses, vault and mandible, and
presenting as a homogeneous, sharply defined bone mass arising from bone surface;
its signs and symptoms are rare and depend on the tumor size and location--e.g.
sinusitis, headache, exophthalmos, diplopia. Osteoid osteoma is a painful highly
vascularized benign tumor usually affecting the long bone diaphysis cortex of
young patients; it generally appears as a small radiolucent nidus with or without
central calcification and surrounding bone sclerosis on radiographs, and as a
'hot' spot on scintigraphy. CT is the method of choice for the definite location
of the nidus especially in sites of complex anatomy, such as the spine, pelvis
and hindfoot. Osteoblastoma is a rare tumor, histologically similar to osteoid
osteoma but with a significantly different clinical potential because of the
possibilities of postoperative recurrence, of its locally aggressive behavior or,
rarer still, malignant transformation; the spine and long bones are affected in
more than half the cases. Its radiologic appearance is not always distinctive and
usually characterized by a lytic lesion with varying bone production and
expansile behavior; CT and MRI are required for the diagnosis of spinal
osteoblastomas. When a bone-producing tumor or tumor-like lesion is suspected but
no specific diagnosis can be made, the knowledge of the range of the imaging
findings of these lesions will allow a suitably ordered differential diagnosis.
Radiography is the single most effective imaging method in this respect. CT is
required for the tumors in complex anatomical sites, such as the spine, pelvis
and hindfoot, as well as for the optimal assessment of the tumor matrix. MRI is
specifically required to study the lesion effect on the spinal canal.
PMID- 9652510
TI - Semeiotics of bone tumors in children.
AB - In recent years, the study of bone disorders has changed thanks to the
progressive development of imaging techniques. In our opinion, however, different
from what happens in the study of pathologic conditions in other organs and
systems, conventional radiology remains the diagnostic cornerstone for bone
disorders and especially bone tumors. In any case, plain radiography must always
be performed first. The radiologic approach to primary bone tumors includes a
series of steps to collect the necessary information to suggest, with the
following contribution of radiography, the most likely diagnosis. The approach is
basically statistical and many parameters should be considered. As far as bone
tumors in children are concerned, the basic role of the statistical variable
'patient age' is apparent and this information should be considered even before
any others. Despite the difficulties in assessing the frequency of bone tumors we
tried to read homogeneously some of the statistical data reported in literature.
Tumor incidence in a given age class is a very important diagnostic tool. Lesion
location is the second step in the radiologic work-up: the involved bone and bone
segment should be assessed and correlated with the preferential site of a
specific tumor. Regarding the bone tumors detected in the first 5 years of life,
an interesting question is whether a vertebra plana is due to a benign or a
malignant lesion. The lytic lesion will be well defined by CT and MRI will be
very useful in depicting bone marrow and surrounding soft tissue involvement.
However, many processes have a similar imaging pattern. We believe that before
biopsy the frequent, marked infiltration of surrounding soft tissues in vertebra
plana should suggest a diagnosis of malignant tumor rather than of tumor-like
lesion.
PMID- 9652511
TI - The value of imaging in the diagnosis and treatment of bone tumors.
AB - The authors report their experience in the diagnosis of bone tumors at the
Rizzoli Institute of Bologna. The main imaging techniques used to this purpose
are conventional radiography, CT, MRI, and isotope bone scan. Angiography is
rarely used. Conventional radiography is the examination of choice and is
sufficient in several benign lesions not requiring treatment. Supplementary
imaging studies are usually needed when radiographic findings are questionable
and/or the lesion requires treatment. When a biopsy is required, it should be
carried out after a complete imaging work-up, which sometimes allows a correct
prebiopsy diagnosis, indicates the biopsy modality, approach and site, and is
also mandatory to stage the tumor, plan the surgical approach and technique, and
show in the finest details the occult tumor spread. CT best shows mineralized
tissues and pulmonary metastases. It is also frequently used as a guide for
needle biopsies. MRI beautifully shows the different tissues and compartments and
it is particularly sensitive in depicting fat. Moreover, it can be repeated many
times, even in pregnant women, because it needs no ionizing radiations and
iodinated contrast; it is also free of artifacts in the patients with orthopedic
devices which are usually nonferromagnetic. However, the execution of an adequate
MRI requires experience and knowledge of bone pathologic conditions. Bone scan
helps in detecting any 'active' area in the bone. It can be thus useful to depict
lesion quiescence or activity and to stage any tumor which can metastasize to the
skeleton. Bone scan is also helpful to show bone lesions when they are not
visible on plain radiographs and indicates the tumor response to preoperative
chemotherapy. Angiography is helpful when a preoperative selective embolization
is needed, or when complex vertebral surgery or vascular surgery are planned. The
bad outcome of bone tumors often depends on incomplete, inadequate or
misinterpretated imaging findings.
PMID- 9652512
TI - Nuclear medicine in primary bone tumors.
AB - INTRODUCTION: Conventional radiography is the method of choice to diagnose a
primary bone tumor but in many cases it is necessary to integrate it with nuclear
medicine scintigraphy using several radionuclides, including 67Ga, 201Tl, 99mTc
MIBI and especially 99mTc-diphosphonates. Recently a new technique has been
recently introduced, that is positron emission tomography with 2(18F) fluoro-2
deoxy-D-glucose as radiopharmaceutical. OBJECTIVE: The specific purpose of this
work is to show that nuclear medicine bone scanning is a very important method in
the detection and diagnostic management of primary bone tumors. DIAGNOSIS,
STAGING AND FOLLOW-UP: Three-phase bone scintigraphy, integrated with SPECT, is
clinically useful to confirm the radiologic diagnosis of bone tumor. These
techniques conveniently related to each other and to radiographic findings, can
evaluate the tumor's local aggressiveness, often differentiating benign from
malignant lesions, to monitor treatment efficacy, to permit total body scanning
for the detection of recurrences. Nuclear medicine diagnostic techniques are not
in competition with radiographic tools as CT and MRI which are highly sensitive
in detecting even small lesions thanks to their excellent anatomical resolution.
In questionable cases, we can integrate radiologic imaging with dynamic studies,
in particular with FDG-PET, increasing the specificity of diagnosis and
permitting more accurate follow-up. CONCLUSIONS: Patient management optimization
needs the integration between dynamic nuclear medicine findings and the
anatomical patterns provided by conventional radiology to increase imaging
sensitivity and specificity. Equipe work is determinant to customize the
diagnostic work-up to the individual patient's needs to reduce the cost of
patient management avoiding useless examinations.
PMID- 9652513
TI - Power Doppler sonography: clinical applications.
AB - OBJECTIVE: Color Doppler imaging (CD) has had a great impact on ultrasonography
(US). This technique depicts local flow by encoding an estimate of the mean
Doppler frequency shift at a particular position in color. However, the choice of
the mean frequency shift as the parameter for representing flow in color Doppler
is somewhat arbitrary. Power Doppler ultrasound is a technique that encodes the
power in the Doppler signal in color. This parameter is fundamentally different
from the mean frequency shift. The frequency is determined by the velocity of the
red blood cells, while the power depends on the amount of blood present.
Providing an image of a different property of blood flow, power Doppler has shown
several key advantages over colour Doppler, including higher sensitivity to flow,
better edge definition and depiction of continuity of flow. In this paper we
review the results of power Doppler clinical studies. MATERIALS AND METHODS: All
relevant information available in the literature on the potential clinical
applications of this technique was revised to give a detailed survey. RESULTS:
The increased flow sensitivity and better vascular detailing of power Doppler
have been used to detect flow presence and characteristics in vessels that are
poorly imaged with conventional color Doppler. The improved depiction of tissue
vasculature has shown potential advantages, especially in some areas, such as the
cortex of native kidneys and renal allografts, the prepuberal testis, the infant
hip and the bowel wall, in which color Doppler is not sensitive enough to detect
clinically important, slow and poor flow in small vessels. In inflammatory
conditions, power Doppler was valuable in depicting increased flow in vessels
that are dilated because of inflammatory response. In this field, advantages have
been reported in acute cholecystitis and in inflammatory states of
musculoskeletal tissues. The higher sensitivity to slow flow and the improved
detailing of the course of tortuous and irregular vessels made power Doppler a
promising technique to image intratumoral vessels and, thereby, to ameliorate the
accuracy of color Doppler in predicting the likelihood of benign versus malignant
nature of nodules. Specific flow patterns, missed at color Doppler studies, have
been indicated with power Doppler in some tumors of the liver and breast. In
different settings, power Doppler also permitted to monitor serial blood flow
changes after therapy and to display them as color intensity, allowing the
observer to distinguish flow changes. CONCLUSION: Although the actual role of
power Doppler in changing patient management has not been assessed yet, this
technique can depict flow which was previously undetectable, and thus permits an
easier and more confident diagnosis in body regions where the ultrasound signal
is weak because blood vessels are small.
PMID- 9652514
TI - Transcranial Doppler: state of the art.
AB - INTRODUCTION: Transcranial color Doppler sonography permits the accurate
assessment of intracranial arteries. The latest Doppler units, using the color
and power techniques, can show even very small flow volumes (1 x 1 mm). Low
frequency (2-2.5 MHz) and very focused transducers are used in transcranial color
Doppler. The skull is a very strong barrier for ultrasounds, which requires the
use of some acoustic windows like some thin portions of the skull bone or some
natural skull foramina. The use of echocontrast agents in color Doppler seems to
increase the applications of transcranial studies. OBJECTIVE: (1) To report on
transcranial color Doppler technique and findings. (2) To assess the role of
contrast agents in the visualization of intracranial vessels. (3) To define the
main indications of this technique. MATERIAL AND METHODS: The temporal, the
orbital and the suboccipital are the main acoustic windows used for transcranial
color Doppler studies. We use phased-array transducers (2-2.5 MHz) and,
preferrably, the echocontrast agent. We examined 15 patients with severe internal
carotid artery stenoses after the infusion of Levovist (Schering AG, Berlin,
Germany) suspension (8 ml at 300 mg Galactose/ml, infused at 0.5 ml/s). RESULTS:
Levovist infusion permitted to depict the main intracranial vessels in all cases.
The middle and the anterior cerebral arteries are shown through the temporal
window. The former is the main cerebral artery, it is the easiest to identify and
presents the highest peak systolic velocity. The orbital window can be used to
visualize the ophthalmic artery and the internal carotid artery siphon, while the
vertebral and the basilar arteries are demonstrated through the suboccipital
window. DISCUSSION: We report the most important findings and discuss the main
indications of transcranial color Doppler studies. In addition to flow presence
and direction, the main indices of arterial flow can be measured thanks to
contrast agent administration, namely the peak systolic velocity, the end
diastolic velocity, the resistance index and the pulsatility index. A
morphological assessment of the Willis circle can also be carried out with color
and power Doppler. Functional studies can be performed to assess the residual
autoregulatory function of the cerebral circle in the patients with internal
carotid artery stenosis or occlusion. The development of intracranial collateral
circles can also be studied in these patients. Moreover, the M1 segment of the
middle cerebral artery and the internal carotid artery siphon can be demonstrated
directly. Transcranial color Doppler is also a useful tool to detect vasospasm
after subarachnoid hemorrhage and to monitor blood flow velocity in the middle
cerebral artery during carotid endarterectomy. The assessment of blood supply to
arteriovenous malformations and to intracranial neoplasms is another application.
CONCLUSION: With reference to internal carotid stenoses, the main applications of
transcranial color Doppler are the study of intracranial vessels, of intracranial
arterial stenosis, of arteriovenous malformations and of Willis circle aneurysms,
as well as the monitoring of blood flow velocity during carotid endarterectomy.
Echocontrast agents play an important role in the visualization of intracranial
vessels.
PMID- 9652515
TI - Monitoring treatment response with color and power Doppler.
AB - Color and power Doppler are now widely used to monitor treatment response because
of the latest technologic advances and of the increasing use of echo-enhancing
agents. The assessment of treatment response is based on the amount of necrosis
obtained and changes in local vascularization indicate a successful treatment. To
date, clinical experiences have mainly concerned the treatment of hepatocellular
carcinomas, hyperfunctioning nodules of the thyroid and parathyroid glands and
the neoadjuvant chemotherapy of breast cancer. Aim of this review is to describe
the role and potentials of color and power Doppler in this field. Hepatocellular
carcinomas are currently treated with surgery or percutaneous ethanol injection
and/or chemoembolization. Treatment response can be monitored with color Doppler:
after a successful treatment, color signals are no longer detectable on color
Doppler images. Conversely, the presence of arterial signals indicates persistent
viable tumor. Unfortunately, color Doppler is limited when the hepatocellular
carcinoma is hypovascular, small or deep. Echo-enhancing agents may help overcome
these limitations, although spiral computed tomography or dynamic magnetic
resonance imaging cannot be replaced yet in the definitive assessment of tumor
necrosis. Color and power Doppler are well-established tools in the study of
functioning thyroid and parathyroid adenomas after percutaneous ethanol
injection. Echo-enhancing agents may improve Doppler sensitivity in the detection
of residual viable tissue. Other interesting applications of color and power
Doppler in this field are secondary hyperparathyroidism and hyperfunctioning
thyreopathies (Graves' disease) treated with mercaptoimidazole. The evaluation of
systolic flow velocity in the inferior thyroid artery is more reliable than the
quantitative analysis of color signals in monitoring treatment response in
Graves' disease. In our experience, systolic velocity in the inferior thyroid
artery decreased from 150-250 to 60-80 cm/s after medical therapy. Finally,
Doppler studies have provided good results in the follow-up of breast cancers
after neoadjuvant therapy. In our experience on 18 patients treated with local
parenteral repeated administration of antiblastic drugs, sonography showed no
more signals within the lesion in 16 patients at the end of therapy. In the
remaining two cases with persistent tumor at ultrasound, some color spots were
still present and histopathology confirmed residual tumor cells. In conclusion,
the results of color and power Doppler are encouraging. Thus, we believe that
Doppler will be increasingly used in monitoring treatment response.
PMID- 9652516
TI - Ultrasound contrast agents: basic principles.
AB - INTRODUCTION: Ultrasonography lacked substances to be administered to patients to
improve or increase the diagnostic yield, which is peculiar considering that
contrast agents have long been used with all the other imaging techniques.
Fortunately some contrast agents, most of them consisting in gas microbubbles,
have been recently introduced for ultrasound imaging too: this review will focus
on their history, behavior, current applications and future developments.
Echocontrast agent research is in progress and many new agents are expected to be
marketed this and next year, to be added to Levovist by Schering AG (Berlin,
Germany), to enhance the ultrasound signal safely and effectively. No definitive
conclusions can be drawn yet on the actual merits of each contrast agent, but all
of them seem to be both effective and safe, meaning that their future success
will depend on the relative cost-effectiveness and peculiarities. THE BASIC
PRINCIPLES OF ECHOCONTRAST AGENTS: The microbubbles act as echo-enhancers by
basically the same mechanism as that determining echo-scattering in all the other
cases of diagnostic ultrasound, namely that the backscattering echo intensity is
proportional to the change in acoustic impedance between the blood and the gas
making the bubbles. The different acoustic impedance at this interface is very
high and in fact all of the incident sound is reflected, even though not all of
it will of course go back to the transducer. But the acoustic wave reflection,
though nearly complete, would not be sufficient to determine a strong US
enhancement because the microbubbles are very small and are sparse in the
circulation. Moreover, reflectivity is proportional to the fourth power of a
particle diameter but also directly proportional to the concentration of the
particles themselves. SECOND HARMONIC IMAGING: As we said above, the microbubbles
reached by an ultrasound signal resonate with a specific frequency depending on
microbubble diameter. However, the main resonance frequency is not the only
resonance frequency of the bubble itself and multiple frequencies of the
fundamental one are emitted, just like in a musical instrument. These harmonic
frequencies have decreasing intensity, but the second frequency, known as the
second harmonic, is still strong enough to be used for diagnostic purposes. The
theoretical advantage of the harmonic over the fundamental frequency is that only
contrast agent microbubbles resonate with harmonic frequencies, while adjacent
tissues do not resonate, or else their harmonic resonation is very little. Thus,
using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz)
and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to
show the contrast agent only, without any artifact from the surrounding
anatomical structures, with a markedly improved signal-to-noise ratio. A similar
effect to digital subtraction in angiography can thus be obtained, even though
through a totally different process. Moreover, second harmonic imaging permits to
show extremely small vessels (down to 40 microm) with very slow flow, which would
be missed with a conventional method. B-mode imaging can also depict the
microbubbles in the myocardium suppressing nearly all the artifacts from cardiac
muscle motion. Recently a peculiar behavior of microbubbles has been observed
which may permit contrast agent detection even in capillaries. This method is
variously known as sonoscintigraphy, loss of correlation, stimulated acoustic
emission and transient scattering. The contrast agent microbubbles reached by an
ultrasound beam powerful enough explode producing a strong and very short
backscatter echo which is read by the unit as a Doppler signal and results in a
color pixel where the individual microbubble exploded. CONCLUSIONS: The
microbubble contrast agents developed and introduced as safe and effective echo
enhancers in present-day clinical practice will open up new oppurtunities
PMID- 9652517
TI - Contrast enhancing agents in ultrasonography: clinical applications.
AB - INTRODUCTION: As ultrasound remains a poorly sensitive method, echocontrast
agents make a real difference. At least 29 echocontrast agents are currently on
trial worldwide; their chemical composition, mechanisms of action and possible
clinical applications are different. The state of the art of echocontrast agents
is discussed: their established applications, those expected in the near future
and finally their hypothetical, ideal applications. POTENTIAL CLINICAL
APPLICATIONS: An extravascular and a vascular domain can be considered. The
former includes the gastrointestinal tract and body cavities--both the normal
(bladder, uterus, tubes and so on) and the abnormal (abscesses, fistulas,
pericardium, peritoneum and so on) ones. Echocontrast agents can: (1) create or
improve an acoustic window; (2) distend some organs and fill them with a liquid,
with homogenous attenuation of the ultrasound beam; (3) displace the air
containing intestinal loops; (4) depict the walls, the shape and the contours of
a normal or abnormal cavity; (5) detect abnormal communications, fistulas and
drainages; and (6) evaluate the amount of fluid in the pleural, pericardial or
peritoneal cavities. As for vascular applications, this domain sees the highest
number of echocontrast agents on trial or on the market. The best know of them
are: Levovist (Schering AG, Berlin, Germany), BR1 (Bracco, Milan, Italy) and
EchoGen (Abbott, USA). All these act by enhancing arteries, veins and
capillaries. The clinical applications validated in clinical trials mainly regard
studies in intracranial and neck vessels and the vascularity of upper and
especially lower limbs of renal vessels. Tumor macrovascularity (and in the
future, hopefully microvascularity) can also be studied in parenchymatous and/or
glandular organs, as well as in intra- and extra-abdominal parenchymatous organs
in the periskeletal soft tissues. Clinical validation has also been obtained in
the follow-up of tumors submitted to ablation therapy (chemoembolization, ethanol
injection, thermal ablation) and in echocardiography, both for morphological
studies in the cardiac cavities and for the cardiac wall perfusion. CONCLUSIONS:
In a subgroup of 513 out of 1275 patients examined Europe-wide, the contrast
agent Levovist increased the diagnostic confidence from 27.4 +/- 22.5 to 77.2 +/-
22.5%. Such data encourage further trials to validate current preliminary
results.
PMID- 9652518
TI - New prospects for ultrasound contrast agents.
AB - Considering the several suggestions regarding the future developments of
echocontrast agents, there is a striking difference between the few compounds
actually available on the market and used in clinical practice and those
undergoing experimental clinical trials. It is therefore difficult to predict
what will be the actual impact of these agents in the next future. Future
developments will probably go beyond color enhancement which was the end-point
till a very short time ago. They can be schematically summarized as follows: (1)
development of new substances which enhance both color and gray scales; (2) use
of new-generation substances, such as BR1 (Bracco, Milan, Italy) and EchoGen
(Sonus, Bothell, WA), which use a gas other than air, such as perfluorate
compounds which are more stable and guarantee longer and stronger effects; (3)
use of more complex compounds acting at different levels. For example, SHU 536A
(Sonovist) produces resonance phenomena with the second and third harmonics, and
also stimulated acoustic emission which permits the morphological study of liver
parenchyma. Other promising compounds are liposomes and aerosomes. Among the new
possibilities in recording and observing phenomena, we can distinguish two main
application fields: one is based on the physics of ultrasound and related to the
presence of microbubbles in an acoustic field. These phenomena are generally
obtained increasing the emission acoustic pressure, which eventually results in
microbubble destruction and they are called nonlinear because there is no direct
relationship between emission and return frequencies. These phenomena, which are
detectable only with dedicated equipment, include: the resonance phenomenon with
harmonic emission; intermittent harmonic emission and stimulated acoustic
emission. The other application field is not strictly related to ultrasound
physics and includes all the systems which can detect the presence of microbubles
qualitatively or quantitatively. Other possible applications are related to the
possibility of acquiring not only morphological but also functional data,
especially in cardiology and neurology. Finally, targeted agents are potentially
capable of demonstrating receptor sites or specific molecules, which may open
very interesting therapeutic routes.
PMID- 9652519
TI - The latest in ultrasound: three-dimensional imaging. Part 1.
AB - OBJECTIVE: The state-of-the-art of three-dimensional ultrasound is reviewed to
evaluate technological achievements and future possibilities in diagnosis and in
the follow-up of medical or invasive therapy. MATERIAL AND METHODS: The problems
related to volumetric acquisitions in the tissues of interest to provide three
dimensional images are considered. Three-dimensional images are easier to achieve
with computed tomography because the scanning system of this technique is
automatic and thus provides sequential slices. The same is true for magnetic
resonance imaging which can aquire volumes directly. The problem with ultrasound
lies in the fact that the scans are manual and therefore less precise. To obtain
three-dimensional images these devices are commonly used: manual scanning probes
connected to spatial magnetic evidencers with remote processing; manual scanning
probes connected to spatial magnetic evidencers placed on the patient's
examination table with processing internal to the ultrasound unit; mechanical
probes that can provide volumetric scans; 'matrix' probes. Recent contributions
are discussed relative to three-dimensional applications to cardiology (cardiac
valve studies), obstetrics (malformations), gynecology (uterine malformations and
extensive ovarian disease studies), gastroenterology (diagnosis of pancreatic and
hepatoabiliary tumor extent), uro-nephrology (detection of stones, prostatic
tumors) and finally in the study of rectal carcinomas. CONCLUSIONS: Nearly all
the papers about three-dimensional ultrasound are works in progress because the
technique has not been standardized yet and some of its future diagnostic
possiblities are difficult to foresee. Moreover, 'matrix' probes are still in the
experimental stage. Nevertheless, this technique seems to be able to yield the
best results in: fetal malformations; calculating the volumes of normal and
diseased organs; the follow-up of masses treated with irradiation/chemotherapy or
with alcohol or chemoembolization; the spatial reconstruction of extensive
lesions; the detection of small lesions (metastases); the study of some complex
functions such as cardiac valve dynamics. But the real problem with three
dimensional sonography is not its efficiency but rather its efficacy, that is
which actual role this technique can play in diagnosis and which information it
can add to that obtained with two-dimensional imaging.
PMID- 9652520
TI - The latest in ultrasound: three-dimensional imaging. Part II.
AB - INTRODUCTION: The three-dimensional (3D) reconstruction of ultrasound images has
become a widespread option in ultrasound equipment. Specific softwares have
become available and 3D reconstruction feasible since the early 1990s,
particularly since 1994. POSSIBLE CLINICAL APPLICATIONS: Several clinical
applications are feasible in all parenchymatous organs (mainly the liver and
prostate), hollow viscera (e.g. the bladder and gallbladder), peripheral vessels
(supra-aortic trunks and limb vessels) and central (the aorta and iliac arteries)
or cerebral vessels. Moreover, tumoral vessels in parenchymatous organs can be
reconstructed, and even the fetus in the uterine cavity, with excellent
detailing. The recent introduction of echocontrast agents and second harmonic
imaging has permitted to study normal and abnormal peripheral, central and
parenchymatous vessels, with similar patterns to those obtained with digital
angiography. The spatial relationships between the vascular structures of the
liver, kidney and placenta were studied with 3D ultrasound angiograms. The
applications of this new technique include the analysis of vascular anatomy and
the potential assessment of organ perfusion. THE LATEST APPLICATIONS-
INTRAVASCULAR STUDIES: Some catheters with an ultrasound transducer in the tip
have been tested for intravascular studies. Just like conventional transducers,
they provide two-dimensional (2D) images which are then postprocessed into
longitudinal 3D or volume reconstructions. The former resemble angiographic
images and can be viewed 3D rotating the image along its longitudinal axis.
Volume images, which are more complex and slower to obtain, can be rotated on any
spatial plane and provide rich detailing of the internal vascular lumen. The
clinical importance of intravascular ultrasound with 3D volume reconstructions
lies in the diagnosis of vascular conditions and the assessment and monitoring of
intravascular interventional procedures--e.g. to detect inaccurate deployment of
intravascular stents and endoluminal grafts during the maneuver. Three
dimensional reconstructions involve geometric data assembly and volumetric
interpolation of a spatially related sequence of tomographic cross sections
generated by an ultrasound catheter withdrawn at a constant rate through a
vascular segment of interest, resulting in the display of a straight segment.
Therefore particular care is needed and there are some useful hints to avoid
mistakes. CONCLUSIONS: Three dimensional reconstructions of B-mode and color
Doppler images are no longer a work in progress and their clinical importance and
possible applications are both established and ever-increasing. On the other
hand, independent of the different types of energy used, also computed tomography
and magnetic resonance 3D reconstructions are very useful from a clinical
viewpoint and they have become an established routine technique for both these
methods. It is very likely that 3D volume reconstructions in ultrasound will find
numerous applications in the near future. They may help to increase the
diagnostic confidence and to facilitate diagnosis, intraprocedure monitoring in
interventional radiology and follow-up and also to reduce the number of invasive
examinations with iodinated contrast agents. This could result in cutting the
cost and duration of the most expensive examinations. New, although invasive,
applications can be hypothesized for intravascular or intraluminal catheters with
an ultrasound transducer inside.
PMID- 9652521
TI - Ultrasound transducers.
AB - Sonography is facing a new technological revolution. Recent advances in
ultrasound technology are increasing spatial, contrast and vascular resolution.
Transducers play an important role in achieving these improvements; their
technology is widely reviewed in this paper. Physics and technology relate to
image quality and its clinical potentials. Large annular arrays made the
progression of imaging quality; they are still a very good choice for scanning
superficial structures. New broadband linear arrays approach their quality and
allow to visualize the flow within very small vessels; they permit new harmonic
imaging that reduces image noise and clutter caused by the body wall. New
advances include digital beamformers that work at their best when coupled with
broadband technology. New multi-layer and multi-array scanheads improve the
signal-to-noise ratio and increase the transmitted energy. New transducers and
imaging algorithms allow real-time acquisition of large fields of view and even
of three-dimensional volumes. Further refinement of two-dimensional matrix
transducers will produce high-definition volumetric images. Evolution in
transducers technology permits to interrogate the vessels with higher Doppler
frequencies extending the anatomical perception and opening new fields of
investigation.
PMID- 9652522
TI - Ultrasonography and PACS.
AB - Expectations and problems related to picture archiving and communication systems
handling of ultrasound images are discussed. Sonography has peculiarities that
must be considered when its integration with picture archiving and communication
systems is planned, namely: (1) data volume is about 3 Mb per ultrasound
examination and is usually lower than that of other imaging modalities; this
makes many requirements less strict; (2) color images represent further problems
which can however be solved with systems capable of performing the analog-to
digital conversion in more than 8 bits; (3) the available equipment comes
with/without digital ports; the interfaces between the ultrasound unit picture
archiving and communication systems are usually based on frame grabbing which
might be sufficient for sonography; (4) equipment may be located in different
departments or in private offices. Therefore solutions (mini-PACS limited to
ultrasound, sub-PACS with a modular development, global PACS) are closely related
to the environment. Our personal experience began with the installation of a
commercial system 10 years ago. With respect to sonography, picture archiving and
communication systems allowed a more reliable and quicker retrieval of previous
examinations, the immediate availability of images in different sites throughout
the hospital and to avoid filming. About 70000 ultrasound examinations have been
archived on optical disks, with a mean of ten images per investigation. Since
November 1991, the picture archiving and communication system has been the only
archive where such images can be found. The location of workstations in the wards
allows the almost real-time availability of images and the immediate availability
of reports right after typing. A questionnaire was given to all the hospital's
clinicians and the following advantages were pointed out: no examination
repetition, no unnecessary investigations, shortening of hospitalization time,
impact on treatment choices. Our experience is going on with a new project,
DPACS, providing all the services of the former system and offering a full
integration with RIS both in the hospital and in the city areas and allowing
communication between DICOM and non-DICOM compliant devices.
PMID- 9652523
TI - New applications of ultrasonography: interventional ultrasound.
AB - Since 1975-80, worldwide but mostly in Europe and Japan, sonography has become
the imaging technique of choice for guiding percutaneous interventional
procedures for diagnostic or therapeutic purposes. In the last 10 years, the most
important advances in interventional ultrasound have occurred in therapeutic
applications, fostering and facilitating the development of the so-called
minimally-invasive techniques. Among all these new applications for the treatment
of fluid collections, inflammatory diseases, benign and malignant tumors, the
most recent dramatic advances have occurred in primary and secondary liver
malignancies, which will be the focus of this review. The rationale for the local
treatment of primary and secondary liver cancers differs according to the success
of conventional treatments (e.g. surgery and chemotherapy) and to the survival
rates of such conditions, depending on clinical stage, patient age, associated
diseases, and so on. Ultrasound-guided percutaneous therapies for liver cancer
can be divided into: (1) direct intratumoral injection of chemical agents, such
as ethanol, hot saline and acetic acid; and (2) thermally-mediated techniques,
such as radiofrequency ablation, interstitial laser photocoagulation, microwave
therapy or cryotherapy. Through different mechanisms of action, all these methods
induce cell death by coagulative necrosis. The clinical efficacy of some of these
techniques has been clearly established, like percutaneous ethanol injection in
the treatment of hepatocellular carcinoma. In contrast, experience with the other
techniques is much more preliminary, mostly due to the limited availability of
sufficient clinical trials and to the fascinating speed of technological
development. We review the state-of-the-art of the two most promising techniques,
namely radiofrequency ablation and interstitial laser photocoagulation, and the
present preliminary clinical data in the treatment of hepatocellular carcinomas
and liver metastases. Radiofrequency energy is delivered to the tumors by means
of electrode-needles (14-17 G) electrically insulated along all but the distal
portion of the shaft and percutaneously introduced into the targets under
ultrasound guidance. In the short history of this method, several technologies
have been tested and used, but 'multiple-hook' and 'internal-cooling' electrodes
are currently the leading choices, providing large necrosis volumes (up to 5 cm
in diameter for a single 12-min application with an array of three internal
cooling electrodes) in short sessions, under local or general anesthesia.
Radiofrequency ablation has proved its usefulness in the treatment of
hepatocellular carcinomas, achieving complete necrosis in over 85-90% of cases in
lesions smaller than 5 cm in diameter and in single sessions, with a low rate (<
10%) of local recurrences. In the treatment of liver metastases, whose very poor
responsiveness to percutaneous ethanol injection and other 'chemical' therapies
is extensively reported in the literature, radiofrequency ablation has 65-75%
reported complete efficacy in the control of local tumor growth in lesions not
exceeding 4 cm. Such great efficacy has been so far coupled with very low rates
of major side-effects (< 2%), most of them requiring no surgical repair.
Interstitial laser photocoagulation induces thermally-mediated coagulation
through thin optic (Nd:YAG) fibers percutaneously inserted into the target under
ultrasound guidance. Multiple fibers (beam splitters) are usually required to
achieve a sufficiently wide necrosis volume. The reported success rate (complete
necrosis and local control of tumor growth) ranges 45-75%) of the lesions, mostly
liver metastates from colorectal carcinoma. An equally low rate of complications
is reported for interstitial laser photocoagulation as for radiofrequency
ablation, that is no more than 2-3% of cases. (ABSTRACT TRUNCATED)
PMID- 9652524
TI - Laparoscopic and intraoperative ultrasound.
AB - OBJECTIVE: Intraoperative ultrasound has gradually expanded in the last two
decades to a variety of surgical specialties and has gained an established role
in many surgical procedures. Laparoscopic and thoracoscopic ultrasound are the
latest modes of intraoperative sonography. They have been introduced mainly to
overcome the two major drawbacks of laparoscopy, i.e. the capability of showing
only the surface of the organs and the lack of manual palpation of the anatomical
structures. We review and discuss the established and the most recent
applications of intraoperative and laparoscopic ultrasound. MATERIAL AND METHODS:
The technology, new indications and results of intraoperative and laparoscopic
ultrasound are reviewed. This review is based on the experience gained in our
Institution during more than 500 surgical procedures and the analysis of the
literature on the subject. RESULTS: The yield of intraoperative and laparoscopic
ultrasound consists in confirming preoperative studies and acquiring new data
which would not be available otherwise. An important role of these techniques is
determining the anatomy of the involved organs, thus providing a guidance for
surgery. Both techniques have an important role in surgical decision-making,
particularly with respect to hepatic, biliary and pancreatic malignancies. In
some series the rate of major changes in the surgical strategy can be as high as
38%. A relatively new application of intraoperative ultrasound is the possibility
to perform interstitial therapy of tumors at the time of the initial surgery.
This can be useful, for example, in patients undergoing liver resection, when
other unresectable lesions are found in a different segment or in the
contralateral lobe. Finally, laparoscopic sonography has an important role in
staging abdominal neoplasm, providing more information than preoperative imaging
and laparoscopic exploration. This feature can be used to effectively stage
gastrointestinal malignancies, pancreatic carcinoma, and abdominal lymphomas.
CONCLUSION: The application of intraoperative ultrasound will increase in the era
of minimally access surgery and this will be dependent not only on technical
improvements in ultrasound technology. Indeed, it may be expected that a variety
of open procedures will be performed with videolaparoscopic monitoring and will
need the guidance of laparoscopic sonography. In the future, the staging of
abdominal neoplasm may be markedly improved by laparoscopy combined with
laparoscopic ultrasound; however a cost-benefit analysis of these techniques and
a comparison with preoperative tests should be carried out.
PMID- 9652525
TI - Current uses of diagnostic high-frequency US in dermatology.
AB - OBJECTIVE: The diagnosis of most skin diseases, both focal and diffuse, has long
relied mainly on physical examination findings. The recent introduction of
technologically advanced ultrasound equipment using 20 MHz probes has permitted
the specific application of ultrasound to dermatology. Accordingly, we
investigated whether the findings at very high frequencies can represent a valid
adjunct to clinical assessment in many skin conditions, including neoplasms,
inflammatory states and diseases of unknown origin. MATERIALS AND METHODS: Skin
lesions are studied using high frequency probes, which very clearly detail the
three layers (epidermis, dermis and subcutaneous tissues) forming the normal
skin. The choice of the probes frequency should depend mainly on the lesion
diameters and site. Electronic 7.5-13 MHz linear probes depict flat and regular
surfaces effectively and provide a wider field of surface vision and, therefore,
a wider view than sectorial probes. Water bath sectorial mechanical probes with
10-20 MHz frequency have very superficial focusing and are excellent to study
irregular surfaces. RESULTS: High frequency ultrasound can be usefully correlated
with clinical tests to study focal skin lesions. The diagnosis of most benign
skin cancers is usually made on clinical bases. Ultrasound examinations are
performed preoperatively in questionable cases. Malignant neoplasms appear at
ultrasound as hypoechoic focal lesions, generally with no specific features in
relation to the histologic type; nevertheless, preoperative ultrasound may play
an important role in that it measures the thickness of cutaneous melanoma, which
is a very important prognostic factor. In particular, 20 MHz probes permit to
assess the depth of melanoma invasion. The sonographic evaluation of melanoma
thickness is usually in agreement with histologic findings. 'Satellite'
neoplastic lesions growing near the main tumor can also be revealed. Color and
power Doppler studies may be combined with gray-scale imaging: the identification
of abnormal intra- or peritumoral low-resistance pulsatile flow signals suggests
the malignant nature of the cutaneous lesion. High frequency ultrasound can also
be used to study diffuse cutaneous conditions. Among them, ultrasound can provide
a valid morphologic representation of psoriatic skin lesions and it is also a
noninvasive and accurate method for evaluating the therapeutic efficacy of
antipsoriatic drugs. In scleroderma, sonographic findings vary depending on
disease activity and the patterns vary; therefore, 20 MHz probes may also prove
useful over the other instrumental tools to monitor the disease course and
treatment efficacy in focal scleroderma. Other potential applications include
allergic dermatitis, nodular erythema, dermatomyosis, sarcoidosis, lymphedema of
the limbs and allergologic conditions. Ultrasound can also be used in monitoring
the response to or complications of topic drugs administration, and in the follow
up of focal burns. CONCLUSION: High frequency ultrasound can provide a reliable
morphologic representation of skin lesions but it is also an accurate noninvasive
tool for monitoring the therapeutic efficacy of drugs administration in focal or
diffuse diseases. The application of high frequency studies to dermatology is
very challenging. Indeed, the very high frequency probes up to 20 MHz currently
available are particularly useful for reliable studies. Contrast-enhanced color
and power doppler are very promising techniques. Advancements in technology will
improve the correlation of clinical with high frequency ultrasound findings in
the assessment of several skin diseases.
PMID- 9652526
TI - Contrast media in liver sonography: correlation with enhanced dynamic magnetic
resonance imaging.
AB - Both color Doppler sonography and magnetic resonance are imaging techniques which
do not use ionizing radiations, but despite this common feature there remain many
differences between them. Thus, color Doppler sonography is a cost-effective
technique using mechanical waves and providing real-time images while magnetic
resonance imaging is much more expensive, uses magnetic fields and radiofrequency
energy and provides static images. The former method is very sensitive in
detecting focal liver lesions > 1 cm, but its specificity in characterization is
not as good, not even with the color Doppler technique. The main differences
between color Doppler sonography, with and/or without echocontrast agents, and
contrast-enhanced (Gadolinium chelates) dynamic magnetic resonance imaging in
focal liver lesions can be summarized as follows: (1) magnetic resonance imaging
depicts tumor vascularization only after paramagnetic contrast media injection.
Enhanced images completely depend upon the contrast agent and cannot be achieved
without it. In contrast, color Doppler signal is not modified by the contrast
agent, it just becomes stronger. (2) Contrast-enhanced magnetic resonance signal
(as well as contrast-enhanced computed tomography signal) provides more pieces of
information than color Doppler signal about the flow characteristics of liver
nodules--i.e. it shows not only blood flow (hyper-/hypovascular nodule), but also
the interstitial spread of the agent and its wash-out. For example,
hepatocellular carcinoma and focal nodular hyperplasia have similar perfusion
while agent spread and wash-out decrease very quickly in the former and more
slowly in the latter, except for the low decrease of the central scar. (3) Color
Doppler technology improvements, higher sensitivity to slow flows and better
signal/noise ratio reduce the applications of contrast-enhanced sonography in
focal liver lesions because the agents modify only sensitivity and not the
imaging in slow flow studies. (4) The higher cost of contrast studies is
justified only in selected cases, namely treatment follow-up in the lesions with
rich pretreatment vascularization. Finally, the higher cost of contrast magnetic
resonance studies is justified to increase sensitivity and especially to allow
lesion characterization.
PMID- 9652527
TI - Image quality control in breast ultrasound.
AB - Sonography is well suited for breast studies. Adequate equipment is needed to
acquire high quality images because several technical factors influence
ultrasound images. Thus, the use of high frequency dynamic scanning probes, the
ultrasound beam focusing corrected for the near field, the adjustment of the gain
and image contrast may all interfere with ultrasound beam reflection and
scattering, determined by the heterogeneity of the gland parenchyma. In the last
few years, a line of ultrasound equipment dedicated to this kind of application
has been developed with 'small parts' transducers and frequencies ranging 10-13
MHz. These units can improve the evaluation of superficial structures and provide
diagnostic results that conventional equipment cannot achieve. The higher the
quality, the more a sonographic image corresponds to real anatomy. This
capability depends on the different kinds of system resolution. Axial spatial
resolution is the capability to resolve discrete structures along the beam axis.
Pulse length is inversely proportional to frequency and thus, the higher the
transducer frequency, the better the axial resolution. However, the increase in
frequency reduces the depth of penetration of the ultrasound beam. The spectrum
of frequencies emitted by the crystal has been recently modified in order to
obtain a good trade-off between the beam resolution and its penetration. Indeed,
the development of the multifrequency technology allowed to improve the near
field resolution while retaining a good penetration into the distant field.
Furthermore, the use of compound ceramics with a broad bandwidth helps Doppler
analysis because flow studies are optimized by low frequencies, whereas two
dimensional morphologic imaging is optimized by high frequencies. Lateral spatial
resolution is the capability to resolve discrete structures perpendicular or
lateral to the beam axis. This parameter strictly depends on the size of the
ultrasound beam section and it is optimal only in the focal area. Therefore, it
improves with narrow beams. Several transducers are available in breast
sonography, but the most adequate one is currently the annular transducer. The
equipment should be able to detect even slight differences in acoustic impedance
between the several breast tissues. This may be obtained by optimizing the
dynamic range and the pre- and postprocessing setting. Apart from equipment, two
other technical factors should be optimized to obtain high quality images, namely
beam intensity and gain curve. A new Doppler technique has been recently
introduced: power Doppler, which allows the demonstration of breast nodule
vascularization with higher sensitivity than color Doppler. Finally, a rigorous
examination technique is required to obtain high quality images. In the last few
years, several quality assurance programs have been introduced. Dedicated
phantoms are generally used. Recently, computer systems have been also developed.
PMID- 9652528
TI - What's new in mammography.
AB - Early diagnosis of breast cancer plays the leading role in reducing mortality
rates and improving the patients' prognosis: mammography is the most sensitive
technique currently available for the detection of nonpalpable lesions and
therefore the method of choice. However, mammography has some limitations and the
technique must be improved with technological devices without affecting image
quality. This could be the target to increase diagnostic accuracy. Mammography
sensitivity and specificity are now improved with the digital computer assisted
technique, teleradiology, digital tomosynthesis or digital angiography--used to
study microvascularization--3D imaging or synchrotron light, and laser
mammography. Such other technological devices as Mammospot reduce breast
thickness and provide better breast compression. Digital mammography can be
carried out with film or direct digitization. The advantages of the digital
technique are a shorter examination time, less storage space, electronic image
recording, with image 'adjustments' made by the radiologist, and especially
computerized analysis. The computer aided diagnosis can be defined as the
diagnosis made by the radiologist who considers the results of computerized
analysis as a 'second opinion'. In this way incidental mistakes made by
radiologists, can be corrected by the computer analysis. Computers are a basic
element also in teleradiology, which needs immediate and simultaneous admittance
to the patient's history and permits radiology optimization in rural areas too.
As for tomosynthesis, it permits to study a single slice of the breast without
glandular tissue overlapping, which is useful in dense breasts where the
diagnosis can be made with a lower X-ray dose. Moreover, this method fits the
current mammographic systems easily. 3D imaging is still a work in progress.
Synchrotron mammography is used only on surgery specimens, where it exhibits high
resolution and contrast, depicting structures and details missed by conventional
mammography. Breast DSA allows the study of vessels < 0.20 mm in diameter and of
fine microvascular details; it can also demonstrate neoangiogenesis. Laser
mammography permits bilateral examinations of the breast in 10-15 mins and is
currently used also for breast cancer therapy, although only in animal trials. To
conclude, after reviewing new techniques and evaluating the real cost/benefit
ratio for each of them, conventional mammography remains the most sensitive tool
for breast cancer diagnosis.
PMID- 9652530
TI - MR state of the art.
AB - Magnetic resonance imaging is undergoing continual and progressive evolution. To
make a high quality examination, some requirements are mandatory, such as high
spatial and contrast resolution to identify lesions and high temporal resolution
to characterize them. We review the most important new magnetic resonance
technologies, both those which are already available and used in clinical
practice and those which are still to be developed. We analyze such technologic
and methodolgic features as magnetic field strength, gradients, surface coils,
echoplanar imaging, fat suppression techniques and magnetization transfer,
contrast agents, automatic injectors, image postprocessing, computer assisted
diagnosis, magnetic resonance-guided biopsy and spectroscopy. All these factors
are in continuous evolution and new technologies anticipate, in the near future,
faster examinations with very high spatial and contrast resolution, with magnetic
resonance-guided cytologic and histologic aspiration biopsies, as well as
spectroscopic studies of previously identified lesions. To perform a correct,
state-of-the-art magnetic resonance examination of the breast, we need high
strength gradients with high slew rate and bilateral coils. Finally, we discuss
new technologies and methods which will increase the accuracy of magnetic
resonance studies of the breast, improving image quality and decreasing execution
time. Thus, magnetic resonance spectroscopy, allowing in vivo biochemical tissue
analysis, seems to have high potentials; even though they are still difficult to
define, the technique is sure to have major diagnostic impact also in monitoring
the results to different treatments.
PMID- 9652529
TI - Breast ultrasound and new technologies.
AB - Technological advances are opening new fields of investigation for breast
ultrasound. Specificity and color Doppler, staging and extended clinical roles in
benign conditions are reviewed according to the state-of-the-art technology.
Annular arrays are the best technical choice but new broadband linear arrays
approach their quality and allow to visualize very slow flows within the breast.
Still limitations exist and ultrasound is not suitable for screening. Providing
better definition of normal as well as abnormal features, high-resolution
sonography improves the specificity of the diagnosis for the majority of nodules
and allows a better definition of both local and regional staging in nodular and
diffuse conditions. Color Doppler and contrast media are increasing ultrasound
specificity and are particularly useful in evaluating vascularity during
therapies. Impressive results are achieved in the study of multifocal and
multicentric carcinomas, in determining the degree of tumoral invasion of the
surrounding tissues and of the ducts. Local and regional staging are greatly
improved; the information given to the surgeon is more precise and allows easier
therapeutic decisions. The diagnostic role of high-frequency ultrasound is also
convincing in most benign conditions like inflammations, traumas and duct
ectasia. In most of these conditions sonography is the best imaging modality to
study the disease type and extent. The ability to monitor treatment efficacy or
the natural outcome makes ultrasound and color Doppler a gold standard for breast
inflammations.
PMID- 9652531
TI - Color Doppler sonography.
AB - The authors report the results obtained with color Doppler sonography in the
study of breast conditions. Color Doppler allows to detect the following main
features in breast conditions: the presence of blood flow, vessel arrangement,
vascularization extent, the number of vascular poles. To investigate slow flows,
it is better to use low PRF values (not above 1 KHz) and low filters, while
amplification should be set immediately above the system's noise threshold; the
size of color Doppler box should be adjusted as small as possible to maximize
sensitivity and minimize flash artifacts. In May 1992 to September 1997, 252
patients with solid breast masses were examined with mammography, B-mode, color
Doppler and power Doppler sonography (only 57 cases). We identified
histologically (176 cases) or cytologically (77 cases) 141 carcinomas and 112
benign solid lesions. The diameter of the 141 carcinomas ranged 0.4-4 cm (mean
1.7), while the diameter of benign lesions ranged 0.7-3 cm (mean 1.5). The
malignancy pattern was characterized by hypervascularity (92.9%), irregular and
abundant (54.2%) vascularization and more than one vascular pole. Benign lesions
were avascular (43.4%) with poor and peripheral vascularity (90%) and mostly
showed only one vascular pole. The avascular cancers (10 cases) were three
mucoid, five in situ and two small (0.7 and 0.9 cm) invasive ductal carcinomas.
The six benign lesions with irregular and abundant vascularization and more than
one vascular pole were proved to be two proliferating and three juvenile
fibroadenomas and one phylloid tumor. These results are encouraging and suggest
that this technique can be a useful adjunct to mammography and sonography in the
differential, diagnosis of breast nodules.
PMID- 9652532
TI - Dynamic imaging: scintimammography.
AB - Although mammography remains the technique of choice for the early detection of
breast cancer, new emerging breast imaging techniques such as ultrasound,
magnetic resonance and radionuclide scanning have been investigated and included
in many diagnostic protocols. This overview discusses the current problems
related to radionuclide breast imaging trying to define its role in the
management of women with suspicious breast lesions at mammography. A number of
tumor-imaging agents have been recently used for the differential diagnosis of
malignant and benign lesions in radiographically dense breasts and breasts with
architectural distortions from prior biopsy or surgery or following radiation
therapy. 99mTc-MIBI is the most used tracer which has become the paradigm of this
new class of compounds suitable for breast imaging. The current sensitivity and
specificity rates for breast scintigraphy with 99mTc-MIBI depend on a number of
factors including lesion size and site. Sensitivity and specificity rates and
positive and negative predictive values of 92, 89, 81 and 96%, respectively, have
been reported in a large series of patients with palpable breast lesions, which
figures have been confirmed in many other series. On the contrary, lower
sensitivity has been reported for nonpalpable breast abnormalities or for lesions
smaller than 1 cm. This observation, confirmed by many authors, implies that a
new nonpalpable lesion that is suspicious for malignancy at mammography needs a
histologic diagnosis. We also report the results of our recent studies on
functional imaging with 99mTc-MIBI of the multidrug resistance phenotype in
breast cancer patients. These studies followed an observation that this tracer is
a suitable transport substrate for the P-glycoprotein (P-gp) which is commonly
associated with the development of a multidrug resistance phenotype. We examined
30 patients with histologically confirmed breast carcinoma who had received no
previous chemotherapy or preoperative local irradiation. We found a positive and
significant correlation between the efflux rates of 99mTc-MIBI determined by in
vivo kinetic analysis and the P-gp levels measured in vitro by quantitative
autoradiography in the same tumors (r = 0.62; p < 0.001). More recently, we
tested whether tumor clearance of 99mTc-MIBI can predict the response to
neoadjuvant chemotherapy in patients with locally advanced breast cancer. Thirty
nine patients with stage III disease underwent 99mTc-MIBI scanning before
neoadjuvant chemotherapy and the time to half-clearance of the tracer was
calculated. The patients then received epirubicin and underwent mastectomy after
completing chemotherapy. This study showed that a rapid tumor clearance of 99mTc
MIBI (< or = 204 min) can predict the lack of tumor response to neoadjuvant
chemotherapy with drugs affected by multidrug resistance phenotype in advanced
breast carcinoma patients. However, slower tracer clearance (> or = 204 min) did
not guarantee an objective tumor response to chemotherapy in all patients, in
agreement with the existence of several P-gp-independent mechanisms of drug
resistance. We conclude that the preliminary study of this phenotype would allow
to predict the response to (neo)adjuvant chemotherapy and select the appropriate
treatment regimen for each patient. Finally, radionuclide breast scanning may be
helpful in the differential diagnosis of malignant and benign breast lesions as a
guide to subsequent chemotherapy.
PMID- 9652533
TI - Dynamic MRI of the breast.
AB - OBJECTIVE: To describe the rationale, the technical requirements and the
examination technique of dynamic magnetic resonance studies of the breast and to
assess the role of this method in the clinical diagnostic protocol. MATERIAL AND
METHODS: We reviewed the relative literature and compared the results with our
personal experience. RESULTS: The earliest reports on the possibility of
differentiating carcinoma from benign tissue with magnetic resonance imaging came
from Germany, where in 1986 Heywang and coworkers used T1-weighted spin-echo
sequences before and after i.v. Gd-DTPA administration with an imaging time of
approximately 5 mins and 5 mm slice thickness. With advances in magnetic
resonance technology, Heywang Koebrunner adopted a static three-dimensional fast
low-angle shot technique permitting < 3 mins' imaging time and providing high
resolution with thin slices. This approach may detect even the carcinoma which
occasionally does not enhance in the typical rapid, intense way. A review of 400
biopsy-proved lesions showed that all carcinomas enhanced strongly, all but 5%
rapidly and 85% focally. Over 70% of benign masses exhibited no major contrast
uptake, although some benign tumors and proliferative dysplasias enhanced
strongly. At present, Heywang-Koebrunner use rapid three-dimensional gradient
echo sequences (TR/TE 14/7, FA 25 degrees; at 1.0 T) which have the advantages of
three-dimensional imaging and permit dynamic studies (< 1 min/sequence). The same
sequence is used at our institution. The dynamic technique is advocated by Kaiser
who in 1989 reported preliminary sensistivity and specificity values over 95%.
The time/signal intensity curves revealed the rapid and strong enhancement of
malignancies, the gradual and strong enhancement of the only fibroadenoma
studied, and the gradual and mild contrast uptake of benign dysplasia. In 1992,
in nearly 1000 dynamic examinations, Kaiser and Reiser reported 98.3%
sensitivity, 97.0% specificity, 82.1% predictive value and 97.2% accuracy. The
combination of rapid acquisition with techniques that preserve high spatial
resolution may improve specificity by allowing the study of lesion morphology as
well as of enhancement patterns. A whole-breast imaging technique has been
reported which permits acquisition times < 15 s by partial sampling of the
central k-space region superimposed on high-resolution three-dimensional images.
CONCLUSIONS: Dynamic magnetic resonance imaging of the breast is currently an
important step of the clinical protocol of breast diseases, but there is no
established study protocol yet.
PMID- 9652534
TI - Computerization in breast imaging and diagnosis.
AB - Computerization in breast imaging is very important for activity management and
for the qualitative and quantitative control of the diagnoses. The connection
through a personal computer network is necessary for the simultaneous input of
more data. The activity in our center is completely managed by a specific
software which controls and facilitates the input of all personal,
administrative, history, instrumental and pathological data. The encoded case
history permits quick and accurate data input and the relative information is
easy to understand. Database information can be used to make periodical
administrative and diagnostic reports and queries, to elaborate useful data for
scientific reports and to manage didactic material. The growing use of computers
will permit the exchange of data among breast imaging centers and also create
important data banks for breast cancer studies.
PMID- 9652535
TI - Scintimammography with 99mTc-MDP: experience of the National Cancer Institute of
Naples.
AB - The role of scintimammography with 99mTc-MDP was investigated in patients with
mammographic or clinical evidence of breast lesions, suspicious for malignancy,
in our Department at the National Cancer Institute of Naples. The end-point of
the study was to assess the uselfulness of this test in diagnosing or ruling out
breast cancer in more than 2000 women. Scintimammography results were compared
with those of mammography and ultrasound and categorized according to
histological findings. Overall sensitivity was 92%, specificity was 90%, and
accuracy 91%. Sensitivity was affected by the lesions exceeding 12 mm and
specificity by sclerotic and/or hyaline or myxoid fibroadenomas, which may be
positive. The major advantages of scintimammography appeared in the study of
calcifications without a mass and of the indirect mammographic signs of breast
cancer, such as distortion and asymmetry. Scintimammography with 99mTc-MDP is a
reliable, safe and highly cost-effective procedure to diagnose or to rule out
breast cancer, after mammography and ultrasound have yielded questionable
results.
PMID- 9652536
TI - Aryepiglottic fold: normal topography and clinical implications.
AB - The aryepiglottic folds extend between the arytenoid cartilage and the lateral
margin of the epiglottis on each side and constitute the lateral borders of the
laryngeal inlet. They are involved in physiologic closure mechanisms of the
larynx and in pathologic conditions such as inspiratory stridor. Information on
the normal topography of the aryepiglottic folds is poor and controversial.
Therefore, this region was reinvestigated in serial whole-organ sections of 25
plastinated normal adult human larynges. Dorsally, the right and the left
aryepiglottic folds are separated by the interarytenoid notch and comprise the
corniculate and cuneiform cartilages, as well as numerous groups of mucous
glands. Ventrally, the aryepiglottic folds are adjacent to the peri-epiglottic
adipose tissue. Both regions are clearly separated by several layers of
transversely oriented collagenous fiber layers. The muscular constituent of the
aryepiglottic folds is only poorly developed, and no muscle fibers insert at the
epiglottis. A coherent quadrangular membrane representing a ligamentous
"skeleton" of the aryepiglottic folds is absent. A conspicuous collagenous fiber
layer is found only to strengthen the free dorsal margin of the fold. Both
muscular and ligamentous components may render the aryepiglottic folds
sufficiently tense as to resist inspiratory inward suction in normal cases.
However, pliability must be preserved to guarantee adequate folding in
approximation of the aryepiglottic folds during deglutition. Thereby, the
posterior part of the laryngeal inlet is closed, whereas the anterior part is
probably closed by independent inward bulging of the peri-epiglottic adipose
tissue.
PMID- 9652537
TI - Blood supply of the tensor fasciae latae muscle.
AB - The tensor fasciae latae (TFL) muscle has been successfully harvested as a
myocutaneous flap in reconstructive surgery. Reports on the vascular supply of
this muscle, however, are incomplete or inconclusive. Therefore the arterial
pattern was examined by dissection in 100 injected human cadaveric specimens. It
was observed that whereas 67 muscles were supplied exclusively by a single vessel
derived from the ascending branch of the lateral circumflex femoral (LCF) artery,
13 were supplied by a secondary vessel derived from the same branch, while 20
muscles were supplied by two vessels, the larger one arising as before and the
smaller from the descending branch of the LCF. Our observations reveal that
although the majority of TFL muscles are clinically Type I (one vascular pedicle)
according to the classification of Mathes and Nahai (1981), 20% are actually Type
II (major and minor vascular pedicles).
PMID- 9652538
TI - Biometry of the muscular branches of the median nerve to the forearm.
AB - The aim of this study was to determine the biometry of the muscular branches of
the median nerve to the forearm in ten embalmed upper limbs. We measured the
length of the forearm and the level of origin of each muscular branch of the
median nerve to the forearm from the middle of a line between the medial and
lateral epicondyles. The level of origin of each branch was then calculated as a
percentage of the length of the forearm. Mean length of the forearm was 25 +/-
2.36 cm (range: 22-29 cm). Although the levels of origin of the proximal and
distal nerves to pronator teres, and of the nerves to palmaris longus, flexor
carpi radialis and flexor digitorum superficialis, were quite variable
(coefficient of variation: CV > 48.61%), the level of origin of the anterior
interosseous nerve (CV = 31.24%) and its branches (nerves to flexor pollicis
longus and flexor digitorum profundus, CV = 20.06%) was less variable. These
results suggest that the anterior interosseous nerve of the forearm is probably
the nerve to connect in muscular free transfers in order to restore flexion of
the fingers after damage to the flexor tendons to the forearm. We observed Martin
Gruber communications in six out of ten dissections.
PMID- 9652539
TI - Approach to dissection of the anterior thoracic wall and the entrance to the
thoracic cavity.
AB - Dissection of the anterior chest wall typically precedes the opening of the
thoracic cavity. The techniques for exposing and subsequently reflecting or
removing the structures of the anterior chest wall have been well described.
However, these approaches that involve the systematic dissection of the layers of
tissue overlying the anterior thoracic wall prior to the removal of the anterior
thoracic wall render the pectoral regions and axillas unfit for continued study.
The authors offer an alternative dissection that allows continued access to the
thoracic cavity while maintaining the integrity of the pectoral and axillary
regions. This new technique may facilitate more efficient use and complete study
of each specimen.
PMID- 9652540
TI - Postmortem blood tests for HIV, HBV, and HCV in a body donation program.
AB - A retrospective analysis of the results of blood tests conducted on body donors
received by the Anatomical Gift Registry of the Medical College of Wisconsin
(MCW) was performed. Over the 5-year period from April 1992 through March 1997 a
total of 785 body donors were tested for Human Immunodeficiency Virus (HIV) and
Hepatitis B and C Viruses (HBV and HCV). Eighteen of the 785 donors (2.3%) tested
positive for one of these infectious agents. Two donors were positive for HIV,
six were positive for HBV and ten were positive for HCV. The death certificates
and files of those donors who tested positive were reviewed and the results are
presented here. Blood testing prior to the use of the body donors is an effective
and reasonable way of identifying the presence of these infectious agents, thus
reducing the risk to those who work with cadavers. The cost for the testing at
MCW is about $60 per donor.
PMID- 9652541
TI - Survey of cadaveric donor application files: 1978-1993.
AB - Information derived from application files of potential cadaveric donors to our
body donation program from the period of 1978-1993 was entered into a customized
database to assess the characteristics of people contributing to such a program.
A total of 1,267 application files were reviewed and the following information
analyzed: 1) year of application submission, 2) age, 3) sex, 4) race, 5) marital
status, 6) education, 7) occupation, and 8) disposition of cremains (return or
not to family). Overall the typical body donor applicant to our program was
likely to be a white married female homemaker of about 70 years of age. She was a
high school graduate and chose not to have her cremains returned to her family.
The males closely follow the above mentioned characteristics (with the exception
of occupation), but were outnumbered by females in nearly every category
throughout the span of our analysis. An analysis of the application numbers over
the 15 year period of our survey indicated a reduction in applications during the
period of 1982-1984 and a linear increase of applicant numbers from 1989 to 1993.
Finally, we observed a tendency for married couples to donate together with 32.1%
of our married applicants showing this phenomenon.
PMID- 9652542
TI - Regeneration in the central nervous system: pharmacological intervention,
xenotransplantation, and stem cell transplantation.
AB - The factors inhibiting regeneration in the central nervous system (CNS) have been
elaborated, debated, and studied for the past 70 years. Recent work has pointed
to the fine balance that exists between repair and regeneration following CNS
injury. Growth factors have featured prominently in this debate. In attempts to
tip the scales toward regeneration and functional reconnection to damaged
neurons, pharmacological intervention has come to the fore. However, a perennial
concern has been that much of regeneration may be aberrant, although there is now
evidence to suggest that this fear may have been exaggerated. In searching for
additional avenues for achieving therapeutic reconstruction of damaged neural
pathways, transplantation studies occupy a prominent place in the literature.
Various principles have become established, and these have proved relevant for
all approaches utilizing grafts. Xenotransplantation and stem cell
transplantation are approaches with exciting potential. Circuitry can be
effectively restored by xenotransplantation, including early indications of
integration of pig dopaminergic neurons in Parkinson's disease. The considerable
possibilities offered by the differentiation of neural stem cells into progenitor
cells and then into neurons and glia are explored.
PMID- 9652543
TI - Bilateral supernumerary rectus muscles of the orbit.
AB - A bilateral anomaly of the rectus muscles and a unilateral variation of the
levator palpebrae muscle were found in the right and left orbits of an 84-year
old man. The anomaly was in the form of a supernumerary rectus muscle lying on a
sagittal orientation between the optic nerve and lateral rectus muscle (in the
right orbit) and adjacent to the inferior rectus muscle (in the left orbit). In
each orbit the anomalous muscle originated occipitally from the common tendinous
ring and frontally-near the eyeball-joined the terminal part of the inferior
rectus. On its superior margin the anomalous muscle had, in the right orbit, a
broad (4 mm), and in the left orbit a slender (2 mm) muscular bridge to the
superior rectus muscle. Because of their connection to the superior rectus and
their innervation by N.III the accessory orbital muscles are not deemed to be
vestiges of the retractor bulbi muscle which, with the exception of the primates,
is a typical occurrence in vertebrates and is always innervated by N.VI. Our
anomalous orbital muscle must be explained as a supernumerary rectus muscle. A
further variation occurred in the right orbit: an isolated medial part or belly
of the levator palpebrae muscle (the so-called M. gracillimus). In primates this
variation is known as a remnant of the membrana nictitans (third eyelid of the
amniotes). Ignorance of anomalies in the orbital muscles may lead to confusion
and error in diagnostic identification and surgical exposure.
PMID- 9652544
TI - Anatomical conundrum: unusual position of the aortic arch.
AB - At autopsy on a 72-year-old woman, the aortic arch showed an unusual arrangement,
passing behind the trachea and esophagus and descending on the left side. The
heart was normal, and death was due to unrelated causes. The nature of this
anomaly is considered in respect of embryological development.
PMID- 9652545
TI - A clinical conundrum: unilateral decerebrate rigidity.
AB - A case is described in which, following a motorcycle accident resulting in a
closed head injury, a young woman was rendered unconscious. On examination she
was found to have unilateral decerebrate rigidity. Further clinical and
radiological examination revealed that there was no damage to the limbs,
vertebral column, or spinal cord. Readers are expected to be able to make an
anatomical diagnosis on the basis of the facts presented.
PMID- 9652546
TI - Endocrine mechanisms underlying reproductive toxicity in the developing rat
chronically exposed to dietary lead.
AB - A dose-response study was conducted in a rat model to examine the effects of
lifetime lead exposure on the development of the reproductive system and the
endocrine mechanisms underlying these effects. Time-impregnated female Sprague
Dawley rats (n = 10-15/group) were exposed to lead acetate in the drinking water
at levels of 0.05%, 0. 15%, or 0.45% (w/v) initiated on gestational day 5. At
birth, litters were culled to four male and four female pups. Exposure of dams to
lead was continued until weaning, following which, the pups continued to be
exposed to lead acetate in drinking water until sacrifice. One male and one
female pup from each litter were sacrificed at age 21, 35, 55, and 85 d. A
significant dose-responsive decrease in birth weight and crown-to-rump length was
observed in all lead-exposed litters. However, no marked effects were observed on
anogenital distance/crown-to-rump length ratios. Lead exposure resulted in a
delay in sexual maturity as measured by prostate weight in male pups and time of
vaginal opening in female pups, which increased with lead dose. These disruptions
in reproductive physiology were accompanied by a significant decrease in neonatal
sex steroid levels and suppression of the plasma concentrations of testosterone
(male) and estradiol (female) during puberty. In male pups, this was accompanied
by a significant decrease in plasma luteinizing hormone (LH), elevated pituitary
LH content, and a decrease in plasma testosterone/LH ratios at the highest dose.
In female pups, although no effects were observed on plasma LH concentration, a
similar significant elevation in pituitary LH content was observed during early
puberty. Postpuberty, plasma LH and sex steroid concentrations were unaffected at
any dose in spite of continued lead exposure. No significant effects were
observed on epididymal sperm count in male pups at 85 d of age. In female pups,
estrus cycling was only significantly disrupted at the highest lead dose. These
data suggest that the reproductive axis is particularly sensitive to lead during
specific developmental periods, resulting in delayed sexual maturation produced
by suppression by sex steroid biosynthesis. The mechanisms underlying this appear
to involve lead actions on both LH release and gonadal function. At low,
environmentally relevant blood lead concentrations, adaptation to the continuous
presence of the metal ion occurs and surprisingly little effect is observed on
adult reproductive endocrinology and physiology.
PMID- 9652547
TI - Endocrine mechanisms underlying the growth effects of developmental lead exposure
in the rat.
AB - A dose-response study was conducted to examine the growth suppression associated
with developmental lead exposure in a rat model and to determine the endocrine
mechanisms underlying these effects. Ad libitum intake of lead acetate (0.05% to
0.45% w/v) was initiated in time-impregnated female Sprague-Dawley rats (n = 10
15/group) at gestational day 5. At birth, pups were culled to four male and four
females per litter. Lead exposure of dams continued until weaning, following
which lead exposure of pups was continued until sacrifice at age 2 , 35, 55, and
85 days. Birth weight and prepubertal and pubertal growth rates were
significantly suppressed. Growth rates were suppressed to a much greater degree
in male as compared to female pups. Decreased growth rates were accompanied by a
significant decrease in plasma insulin-like growth factor 1 (IGF1) concentrations
and (1) a significant increase in pituitary growth hormone (GH) content during
puberty in pups of both sexes, (2) a delay in the developmental profiles of the
GH-dependent male-specific liver enzymes cytochrome P-450 CYP2C11 and N-hydroxy-2
acetylaminofluorene sulfotransferase, and (3) continued suppression of these
enzymes in lead-exposed adult male pups. In addition, significant decreases in
plasma sex steroids, testosterone (male) and 17beta-estradiol (female), were
observed during puberty. Postpuberty, at age 85 d, both IGF1 and sex steroid
levels were indistinguishable from control pups despite continued lead exposure.
Growth rates were also similar in control and lead-exposed pups between age 57
and 85 d. Data suggest that the mechanism underlying lead-induced sex-independent
suppression of growth observed in these studies involves disruption of GH
secretion during puberty. It is possible that the mechanisms underlying the
greater suppression of somatic growth observed at puberty in lead-exposed male
offspring may be due to the additional hypoandrogenization produced by the action
of lead on the hypothalamic-pituitary-testicular axis.
PMID- 9652548
TI - Disposition of 2-methylimidazole in rats.
AB - 2-Methylimidazole (2-MI), widely used as a chemical intermediate, is also present
in cigarette smoke and may form in food and forage as a result of ammoniation of
simple sugars. 2-MI has been shown to be neurotoxic in several animal species and
to alter serum levels of T3, T4, and thyroid-stimulating hormone (TSH) in the
rat, apparently leading to hyperplasia of thyroid follicular cells. In order to
better characterize 2-MI-induced toxicity, the disposition of [2-(14)C]-2-MI has
been investigated following p.o. administration of either 5, 50, or 150 mg/kg to
male F344 rats. Excretion data indicated that absorption of 2-MI was both rapid
and proportional to dose in the range studied. Approximately 90% of the total
dose was eliminated in urine within 24 h. Most of the remaining 14C was excreted
in feces and as expired 14CO2. Excretion data were similar following i.v.
administration of 5 mg/kg. Little or no enterohepatic circulation of compound
occurred, since biliary excretion of 2-MI-derived 14C was negligible.
Approximately 70% of the 14C excreted in urine, following all dosing, consisted
of parent compound. High-performance liquid chromatography (HPLC) chromatograms
for all treatment groups were similar, indicating that metabolism of 2-MI in rats
was not affected by dose or route of administration.
PMID- 9652549
TI - 1,1,2,2-Tetrachloroethane-induced early decrease of dolichol levels in rat liver
microsomes and Golgi apparatus.
AB - Dolichols are long-chain polyprenols containing 14-22 isoprene units, present in
mammalian tissues as free dolichol (Free-Dol), fatty acyl dolichyl esters (Dol
FA), and dolichyl phosphate (Dol-P). The hepatic level of Dol-P seems to be a
rate-limiting factor for glycosylation processes. Previous studies from our
laboratory demonstrated the susceptibility of the dolichol molecule to undergo
radical attacks. Since the toxicity of 1,1,2,2-tetrachloroethane (TTCE)is
dependent on the free-radical production during hepatic biotrasformation, it was
of interest to determine whether this haloalkane might affect glycosylation
mechanisms by changing dolichol levels and distribution in rat liver microsomes
and Golgi apparatus (GA). Male Sprague-Dawley rats received a single dose of TTCE
(574 mg/kg body weight) and were then sacrificed at different times (5, 15, 30,
or 60 min). In the TTCE-treated rats both serum aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) activities and hepatic triglycerides (TG) were
significantly higher than control, while microsomal glucose 6-phosphatase
(G6Pase) activity was decreased. In total microsomes Dol-P levels considered rate
limiting for the biosynthesis of the N-glycosylated proteins were significantly
lower than in the control group 15 min after TTCE treatment. In normal rat liver,
F1 secretory fraction of CA is 60-fold enriched in total dolichol content with
respect to microsomes. In this compartment the total dolichol content, essential
for the increase in membrane fluidity and permeability required for glycoprotein
maturation and secretion, decreased significantly 5 min after TTCE treatment. Our
results suggest that TTCE may affect dolichol functions in rat liver.
PMID- 9652550
TI - Estimation of absorption of environmental contaminants in low-level exposure by
pharmacokinetic analysis.
AB - Inhalation pharmacokinetics of the environmental contaminants 1,1,1
trichloroethane, tetrachloroethylene, trichloroethylene, benzene, and p
dichlorobenzene were determined in male Sprague-Dawley rats, and data generated
were used to obtain fundamental data for risk assessment of chronic low-level
exposures to these substances. Measured amounts of the substances were injected
into a closed chamber system in which a rat had been placed, and the
concentration changes in the chamber air were examined. The pharmacokinetics of
the substances were evaluated using linear or nonlinear compartment models. The
metabolic elimination amounts at various exposure concentrations were
extrapolated using the estimated pharmacokinetic parameters. At low (1 ppb)
concentration exposure to benzene or trichloroethylene the fraction of
elimination of these substances was 1.6 and 1.5 times higher, respectively, than
that seen at high (10 ppm) concentration exposure. Extrapolation kinetics of low
exposure data showed more trichloroethylene (0.0016 micromol/h/kg), benzene
(0.0014 micromol/h/kg), and p-dichlorobenzene (0.00052 micromol/h/kg) was
absorbed by the rats than 1,1,1-trichloroethane (0.000019 micromol/h/kg) and
tetrachloroethylene (0.000029 micromol/h/kg). Although the exposure
concentrations for all chemicals were equal, the differences in absorption
quantities need to be considered in evaluation of potential risk assessment.
PMID- 9652551
TI - Cadmium suppresses apoptosis induced by chromium.
AB - Cadmium and chromium are both well-known human carcinogens, and common exposures
to these metals are not infrequent. Recent studies have shown that hexavalent
chromium induces apoptosis in Chinese hamster ovary (CHO) cells, suggesting an
association of apoptosis with carcinogenesis. In contrast, induction of apoptosis
by cadmium has been inconsistently observed. The present study was designed to
determine if cadmium could induce apoptosis in CHO cells and if common exposure
to cadmium and chromium would modify any apoptotic response. Apoptosis was
evaluated by both agarose gel and in situ end-labeling methods. Apoptosis was
observed at 48 h after treatment with 300 microM chromium (Na2CrO4) for 2 h.
Cadmium alone at concentrations of 1, 5, or 10 microM (as CdCl2) did not induce
apoptosis in these cells even at times up to 72 h after treatment. However, when
CHO cells were concurrently exposed to cadmium and chromium, chromium-induced
apoptosis was markedly suppressed in a cadmium concentration-related fashion.
Cadmium did not consistently modify the cytotoxic effects of chromium, and
significant increases in metallothionein were not induced by these metal
treatments. These findings indicate that cadmium can block chromium-induced
apoptosis. The suppression of apoptosis by cadmium may be a significant aspect of
its carcinogenic mechanism.
PMID- 9652552
TI - Working for safe and healthy work.
PMID- 9652553
TI - Does IGF-I therapy in insulin-dependent diabetes mellitus limit complications?
PMID- 9652554
TI - Platelet glycoprotein IIIa polymorphism and coronary thrombosis.
PMID- 9652555
TI - Odour perception in chronic renal disease.
PMID- 9652556
TI - Antibiotic prophylaxis after tick bites.
PMID- 9652557
TI - It's my book.
PMID- 9652558
TI - Vaccines 1997.
PMID- 9652559
TI - Randomised trial of basiliximab versus placebo for control of acute cellular
rejection in renal allograft recipients. CHIB 201 International Study Group.
AB - BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney
recipients are far from ideal because acute-rejection episodes occur in about 30%
to 50% of these patients. In the phase III study described here we assessed the
ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal
antibody, to prevent acute-rejection episodes in renal allograft recipients.
METHODS: 380 adult recipients of a primary cadaveric kidney transplant were
randomly allocated, in this double-blind trial, to receive a 20 mg infusion of
basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor
suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups
received baseline dual immunosuppressive therapy with cyclosporin and steroids
throughout the study. The primary outcome measure was incidence of acute
rejection episodes during the 6 months after transplantation. Safety and
tolerability were monitored over the 12 months of the study. FINDINGS: 376
patients were eligible for intention-to-treat analysis (basiliximab, n=190;
placebo, n=186). No significant differences in patient characteristics were
apparent. The incidence of biopsy-confirmed acute rejection 6 months after
transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73
(44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan
Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first
rejection episodes that required antibody therapy was significantly lower in the
basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At
weeks 2 and 4 post-transplantation, the mean daily dose of steroids was
significantly higher in the placebo group (p<0.001 with one-way analysis of
variance). The incidence of graft loss at 12 months post-transplantation was 23
(12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo
group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and
other adverse events was similar in the two treatment groups. The acute
tolerability of basiliximab was excellent, with no evidence of cytokine-release
syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%],
p=0.293) occurred during the 12-month study and a further three deaths
(basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One
post-transplantation lymphoproliferative disorder was recorded in each group.
INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute
rejection episodes significantly, with no clinically relevant safety or
tolerability concerns.
PMID- 9652560
TI - Randomised placebo-controlled trial of human recombinant insulin-like growth
factor I plus intensive insulin therapy in adolescents with insulin-dependent
diabetes mellitus.
AB - BACKGROUND: Good glycaemic control in insulin-dependent diabetes mellitus (IDDM)
to prevent complications may be difficult to achieve during adolescence, because
abnormalities in production of growth hormone or insulin-like growth-factor-I
(IGF-I) can lead to lower insulin sensitivity. Recombinant human IGF-I (rhIGF-I)
given as an adjunct to insulin therapy in IDDM, might improve glycaemic control
in adolescents; we investigated the effects of the addition of IGF-I in a
randomised, double-blind, placebo-controlled trial. METHODS: 53 patients with
IDDM (26 male, 27 female) with a median age of 16.1 years (range 10.8-20.6) and
diabetes of more than 2 years' duration were randomly assigned subcutaneous rhIGF
I (20 or 40 microg/kg daily [n=18, n=18, respectively]) or placebo (n=17), both
in addition to multiple-injection insulin therapy for 24 weeks. The primary
endpoint, glycated haemoglobin (HbA1c) and routine biochemistry were measured
every 4 weeks. Retinal photographs and glomerular-filtration rates were assessed
at base line and at the end of the study. Data were analysed by intention to
treat. FINDINGS: With a dose of 40 microg/kg rhIGF-I daily, we found significant
reductions in HbA1c compared with placebo (p=0.03), without changes in body-mass
index, rate of hypoglycaemia, insulin dose, or circulating concentrations of IGF
binding proteins 1 and 3. The greatest median change in HbA1c of -0.6% (range
2.8 to -1.5%) was seen with rhIGF-I 40 microg/kg at week 12, but was not
sustained at week 24. The greatest reductions in HbA1c at week 24 were seen among
patients with the greatest changes in IGF-I concentrations (r=-0442, p=0.002).
Retinal photographs, renal function (glomerular filtration rate and urinary
albumin excretion), and routine biochemistry showed no adverse events.
INTERPRETATION: Our data confirm that rhIGF-I as an adjunct to insulin therapy
can improve HbA1c values in adolescents with IDDM without overt toxic effects,
but they raise questions about whether these effects can be sustained in cases of
poor compliance or reduced bioefficacy.
PMID- 9652561
TI - Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine
for prevention of severe rotavirus gastroenteritis.
AB - BACKGROUND: Rotavirus is the most common cause of acute childhood
gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may
prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human
reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus
gastroenteritis in Finnish children in a randomised placebo-controlled double
blind trial. METHODS: Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was
given to infants at ages 2, 3, and 5 months. The children were followed up for
one or two rotavirus epidemic seasons. The main outcome measure was protection
against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity
scale). 2398 children were enrolled and received at least one dose of RRV-TV
(n=1191) or placebo (n=1207). The primary efficacy analysis was based on children
who received three doses of RRV-TV (n=1128) or placebo (n=1145). FINDINGS: 256
episodes of rotavirus gastroenteritis occurred at any time during the study; 65
were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine
efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were
included in the primary efficacy analysis of fully vaccinated children (54 among
1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68%
[57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo
recipients (vaccine efficacy 91% [82-96]). INTERPRETATION: RRV-TV vaccine was
highly effective against severe rotavirus gastroenteritis in young children.
Incorporation of this vaccine into routine immunisation schedules of infants
could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis
of all causes in young children by 60%.
PMID- 9652562
TI - Long-term follow-up of patients from a randomised trial of atrial versus
ventricular pacing for sick-sinus syndrome.
AB - BACKGROUND: In a previous study of 225 patients with sick-sinus syndrome
randomised to either single-chamber atrial pacing (n=110) or single-chamber
ventricular pacing (n=115), we found that after a mean follow-up of 3.3 years,
atrial pacing was associated with significantly less atrial fibrillation and
thromboembolism whereas there was no significant difference in mortality and
heart failure between the two groups. We aimed to find out whether this
beneficial effect of atrial pacing is maintained during extended follow-up of up
to 8 years. METHODS: Follow-up visits for all patients were at 3 months, 12
months, then once a year at which patients had a physical examination, ECG
recording, and pacemaker check-up. Endpoints were mortality, cardiovascular
death, atrial fibrillation, thromboembolic events, heart failure, and
atrioventricular block. Data was analysed on Dec 31, 1996. FINDINGS: At long-term
follow-up, 39 patients from the atrial group had died versus 57 from the
ventricular group (relative risk 0.66 [95% CI 0.44-0.99]; p=0.045). 19 patients
from the atrial group and 39 patients from the ventricular group died from a
cardiovascular cause (0.47 [0.27-0.82]; p=0.0065). The cumulative incidences of
atrial fibrillation and chronic atrial fibrillation were also significantly lower
in the atrial group than in the ventricular group (0.54 [0.33-0.89], p=0.012 and
0.35 [0.16-0.76], p=0.004, respectively). Thromboembolic events occurred in 13
patients in the atrial group and 26 in the ventricular group (0.47 [0.24-0.92],
p=0.023). Heart failure was less severe in the atrial group than in the
ventricular group (p<0.05). In multivariate analysis, atrial pacing was
significantly associated with freedom from thromboembolic events (0.47 [0.24
0.92], p=0.028) and survival from cardiovascular death (0.52 [0.30-0.91],
p=0.022), but no longer with overall survival (0.71 [0.46-1.08], p=0.11) or
chronic atrial fibrillation (0.45 [0.20-1.05], p=0.063). Atrioventricular block
occurred in four patients in the atrial group (0.6% annual risk). INTERPRETATION:
The beneficial effect of atrial pacing found in our previous study is enhanced
substantially over time. Patients with sick-sinus syndrome should be treated with
an atrial rather than ventricular-pacing system because after long-term follow
up, atrial pacing is associated with a significantly higher survival, less atrial
fibrillation, fewer thromboembolic complications, less heart failure, and a low
risk of atrioventricular block.
PMID- 9652564
TI - Loss of control after a cup of coffee.
PMID- 9652563
TI - Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis.
AB - BACKGROUND: Coronary stents are an effective treatment for selected coronary
stenoses. However, thrombosis of the stented segment is a major adverse
complication. Platelet aggregation has a key role in stent thrombosis. We
investigated whether a polymorphism of platelet glycoprotein IIIa gene (PIA2) is
associated with an increased risk of coronary stent thrombosis. METHODS: 318
consecutive patients were followed up for 30 days after coronary stent insertion.
The primary endpoints were death, myocardial infarction, stent-vessel occlusion,
and coronary artery bypass surgery. Gel electrophoresis of PCR products was used
to identify the PIA1 and PIA2 alleles. The relative risk of stent occlusion was
calculated from the odds ratio on logistic regression analysis. FINDINGS: 63
(19.8%) of patients had the PIA2 allele and 255 (80.2%) were homozygous for PIA1.
Baseline clinical, angiographic, and procedural features did not differ between
the groups with and without the PIA2 allele. Occlusion of the stent vessel
occurred in five (1.9%) patients homozygous for PIA1 and six (9.5%) patients with
PIA2 allele (odds ratio 5.26 [95% CI 1.55-17.85]). On multivariate regression
analysis PIA1/A2 genotype was the only significant independent predictor of stent
thrombosis. INTERPRETATION: Patients with the pIA2 allele have an increased risk
of coronary stent thrombosis, which may warrant antiplatelet therapy with
glycoprotein-IIb/IIIa inhibitors, although bleeding complications may also
increase.
PMID- 9652565
TI - Magnetic resonance neurography of peripheral nerve degeneration and regeneration.
PMID- 9652567
TI - Mutations in the MEN I gene in sporadic neuroendocrine tumours of
gastroenteropancreatic system.
PMID- 9652568
TI - Pseudolymphoma at site of clonidine patch.
PMID- 9652566
TI - Simvastatin reduces monocyte-tissue-factor expression type IIa
hypercholesterolaemia.
PMID- 9652569
TI - Bilateral dorsolateral subthalamotomy for advanced Parkinson's disease.
PMID- 9652570
TI - Previous cytomegalovirus or Chlamydia pneumoniae infection and risk of restenosis
after percutaneous transluminal coronary angioplasty.
PMID- 9652571
TI - Monitoring compliance with antituberculous treatment by detection of isoniazid in
urine.
PMID- 9652572
TI - Microscopic haematuria: a diagnostic aid in giant-cell arteritis?
PMID- 9652573
TI - UK report calls for additional smear test re-reads.
PMID- 9652576
TI - Human rights give way to civil rights in Argentina.
PMID- 9652575
TI - M cells: portals to the mucosal immune system.
PMID- 9652578
TI - World Bank's policy of structural adjustment under fire in India.
PMID- 9652577
TI - Ireland rules out compulsory HIV testing.
PMID- 9652579
TI - Struggle worldwide to regain consumers' faith in food.
PMID- 9652580
TI - Portal hypertension and variceal haemorrhage.
PMID- 9652581
TI - Applications of molecular microbiology to vaccinology.
AB - Genetics, cell biology, and whole-genome sequencing of pathogens have changed
dramatically the opportunities to investigate the epidemiology, pathogenesis,
diagnosis, and control of microbial diseases. For example, recombinant DNA and
PCR are powerful tools used to isolate genes whose role in pathogenicity can be
investigated in biologically relevant virulence assays. Vaccines that target one
or more of these genes can then be developed. Complete genome sequences of
microbes provide an inventory of the genes encoding every virulence factor and
potential immunogen. Candidate vaccines can be selected and developed using
various approaches, including the recent innovation of immunisation with nucleic
acids. Although many successful vaccines have been and will continue to be
developed through empirical approaches, molecular microbiology provides a
rational basis for discovery, development, and implementation of safer, more
effective and, potentially cheaper vaccines.
PMID- 9652582
TI - Osler and Ernulf's curse.
PMID- 9652583
TI - The truth about Israeli medical ethics.
PMID- 9652584
TI - Stress and long-term coronary risk.
PMID- 9652585
TI - Liver abnormalities and hydrochlorofluorocarbons.
PMID- 9652586
TI - Liver abnormalities and hydrochlorofluorocarbons.
PMID- 9652587
TI - Paraneoplastic limbic encephalitis.
PMID- 9652588
TI - Paraneoplastic limbic encephalitis.
PMID- 9652589
TI - HIV-1 infection associated with abnormal vaginal flora morphology and bacterial
vaginosis.
PMID- 9652590
TI - HIV-1 infection associated with abnormal vaginal flora morphology and bacterial
vaginosis.
PMID- 9652591
TI - Childhood idiopathic thrombocytopenic purpura.
PMID- 9652592
TI - Childhood idiopathic thrombocytopenic purpura.
PMID- 9652593
TI - Chorionic villus sampling versus early amniocentesis.
PMID- 9652594
TI - Chorionic villus sampling versus early amniocentesis.
PMID- 9652595
TI - GTP-cyclohydrolase and vitiligo.
PMID- 9652597
TI - East-West mortality gap and environment.
PMID- 9652596
TI - Left-ventricular dysfunction in diabetic patients with leucine tRNA mutation.
PMID- 9652598
TI - Population growth in Africa.
PMID- 9652599
TI - Authorship of complex investigations.
PMID- 9652600
TI - Risk factor epidemiology.
PMID- 9652601
TI - A thirst for progress in patients' care.
PMID- 9652602
TI - Loaded, but no place to go.
PMID- 9652603
TI - More clinical judgment, fewer "clinical" judges.
PMID- 9652604
TI - Prognosis of BRCA1 hereditary breast cancer.
PMID- 9652605
TI - Insulin-sensitising agents in polycystic-ovary syndrome.
PMID- 9652606
TI - Screening for urinary abnormalities: worth doing and worth doing well.
PMID- 9652607
TI - Not all is dead in HIV-1 graveyard.
PMID- 9652608
TI - Measuring height: to stretch or not to stretch?
PMID- 9652609
TI - Number-needed-to-treat and placebo-controlled trials.
PMID- 9652610
TI - Recurrence risks in offspring of adults with major heart defects: results from
first cohort of British collaborative study.
AB - BACKGROUND: Congenital heart defects are generally assumed to have a
multifactorial aetiology. We have tested this hypothesis by studying adults with
heart defects and their families. METHODS: We identified 1094 patients who
survived surgery for major cardiac defects before 1970. We chose individuals with
disturbance of situs or segmental connection, with atrioventricular septal defect
or with tetralogy of Fallot. After exclusion and non-participation, 727
individuals were traced. Each was visited by an investigator and completed a
detailed questionnaire. If possible, all "normal" offspring were examined by a
paediatric cardiologist. FINDINGS: The 727 individuals had 393 live offspring.
There were 71 miscarriages and five terminated pregnancies. Overall, we found
recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This
result differed significantly from sibling risk (2.1%; p=0.021). More congenital
heart defects occurred in the offspring of affected women than in those of
affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the
offspring were taken into account the excess was more significant (p=0.032). We
found an excess of miscarriages in the offspring of affected women (p=0.001). In
tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12
(2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight
(0.3%) of 2728 third-degree relatives. INTERPRETATION: Our findings do not
support a polygenic basis for all heart defects. Atrioventricular septal defect
seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder
with a small number of interacting genes. Our data suggest that isolated
transposition of the great arteries is a sporadic defect.
PMID- 9652611
TI - Survival and tumour characteristics of breast-cancer patients with germline
mutations of BRCA1.
AB - BACKGROUND: Hereditary breast cancer has been associated with mutations in the
BRCA1 and BRCA2 genes and has a natural history different from sporadic breast
cancer. We investigated disease-free and overall survival for patients with a
proven BRCA1 alteration. METHODS: We estimated disease-free and overall survival
for 49 Dutch patients from 19 consecutive families with a proven specific BRCA1
mutation and one family with strong evidence for linkage to the BRCA1 gene. We
compared clinical outcome and data on tumour size, histology, axillary nodal
status, contralateral breast cancer, and oestrogen-receptor and progesterone
receptor status with those of 196 patients with sporadic breast cancer, matched
for age and year of diagnosis. FINDINGS: Disease-free survival for BRCA1 and
sporadic patients at 5 years was 49% (95% CI 33-64) and 51% (43-59), respectively
(p=0.98). Overall survival at 5 years was 63% (47-76) and 69% (62-76),
respectively (p=0.88). Recurrence and death rates did not differ significantly
between groups. Hazard ratios for recurrence and death among BRCA1 patients were
1.00 (0.65-1.55) and 1.04 (0.63-1.71) relative to sporadic patients (p=0.88), and
these did not differ significantly after adjustment for prognostic factors.
Patients with BRCA1-associated breast cancer had twice as many progesterone
receptor-negative tumours (p<0.005) and development of contralateral breast
cancer was four to five times as frequent as in the sporadic group (p<0.001).
INTERPRETATION: We showed that disease-free and overall survival were similar for
sporadic and hereditary breast cancer in the presence of different tumour
characteristics, which has implications for screening prophylactic therapy, and
different treatments of hereditary breast cancer.
PMID- 9652612
TI - Randomised trial of laparoscopic versus open cholecystectomy for acute and
gangrenous cholecystitis.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice
for elective cholecystectomy, but controversy persists over use of this approach
in the treatment of acute cholecystitis. We undertook a randomised comparison of
the safety and outcome of LC and open cholecystectomy (OC) in patients with acute
cholecystitis. METHODS: 63 of 68 consecutive patients who met criteria for acute
cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The
primary endpoints were hospital mortality and morbidity, length of hospital stay,
and length of sick leave from work. Analysis was by intention to treat. Suspected
bile-duct stones were investigated by preoperative endoscopic retrograde
cholangiography (LC group) or intraoperative cholangiography (OC group).
FINDINGS: The two randomised groups were similar in demographic, physical, and
clinical characteristics. 48% of the patients in the OC group and 59% in the LC
group were older than 60 years. 13 patients in each group had gangrene or
empyema, and one in each group had perforation of the gallbladder causing diffuse
peritonitis. Five (16%) patients in the LC group required conversion to OC, in
most because severe inflammation distorted the anatomy of Calot's triangle. There
were no deaths or bile-duct lesions in either group, but the postoperative
complication rate was significantly (p=0.0048) higher in the OC than in the LC
group: seven (23%) patients had major and six (19%) minor complications after OC,
whereas only one (3%) minor complication occurred after LC. The postoperative
hospital stay was significantly shorter in the LC than the OC group (median 4
[IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in
the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7).
INTERPRETATION: Even though LC for acute and gangrenous cholecystitis is
technically demanding, in experienced hands it is safe and effective. It does not
increase the mortality rate, and the morbidity rate seems to be even lower than
that in OC. However, a moderately high conversion rate must be accepted.
PMID- 9652613
TI - Randomised placebo-controlled crossover trial on effect of inactivated influenza
vaccine on pulmonary function in asthma.
AB - BACKGROUND: Despite current recommendations, many people with asthma do not
receive annual vaccination against influenza, partly because of concern that
vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be
mistaken for vaccine-related adverse events. We undertook a double-blind placebo
controlled multicentre crossover study to assess the safety of influenza vaccine
in patients with asthma, with allowance for the occurrence of colds. METHODS: We
studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow
(PEF), respiratory symptoms, medication, medical consultations, and hospital
admissions for 2 weeks before the first injection and until 2 weeks after the
second injection. Order of injection (vaccine and placebo) was assigned randomly.
There was an interval of 2 weeks between injections. The main outcome measure was
an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of
>20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in
PEF of more than 20% after vaccine compared with three after placebo (McNemar's
test p=0.06); a fall of more than 30% was recorded by eight after vaccine
compared with none after placebo (binomial test p=0.008). However, when
participants with colds were excluded, there was no significant difference in the
numbers with falls of more than 20% between vaccine and placebo (six vs three;
binomial test p=0.51), although the difference for PEF decreases of more than 30%
approached significance (five vs none; binomial test, p=0.06). This association
was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that
pulmonary-function abnormalities may occur as a complication of influenza
vaccination. However, the risk of pulmonary complications is very small and
outweighed by the benefits of vaccination.
PMID- 9652614
TI - Lung as reservoir for antidepressants in pharmacokinetic drug interactions.
AB - BACKGROUND: Although high-affinity imipramine binding sites have been reported in
both rat and human lung, the role of the lungs in the pharmacokinetics of
antidepressants has not received much attention. Substantial accumulation of
selective serotonin-reuptake inhibitors (SSRIs) in the lungs has been reported.
We have investigated the role of the lungs in pharmacokinetic drug interactions
between tricyclic antidepressants and SSRIs. METHODS: We used a carbon-11
labelled form of the imipramine derivative cyanoimipramine to measure uptake in
the lungs and brain of healthy volunteers by positron emission tomography.
Clomipramine (50 mg) was administered to measure the effect of antidepressants
with high affinity for the serotonin transporter on lung and brain uptake.
FINDINGS: A large proportion of the injected 11C-cyanoimipramine (68-86% in the
four volunteers) was extracted by the lungs. Clomipramine decreased the lung
uptake from 68% to 35% and from 81% to 54% in the two volunteers studied. By
contrast, whole-brain uptake was low in control studies (1.7-2.0% in three
volunteers) and increased after clomipramine administration (to 4.5-4.9%). Plasma
radioactivity was also higher after clomipramine than in control studies.
INTERPRETATION: The lungs may function as a reservoir for antidepressants with
high affinity to the serotonin transporter. The accumulated antidepressants may
be displaced by other antidepressants, and this displacement would substantially
increase plasma concentrations and thus cause toxic effects.
PMID- 9652615
TI - Wobbly handwriting.
PMID- 9652616
TI - Cosmetic results and patient satisfaction with secondary wound healing after
abdominal surgery.
PMID- 9652617
TI - Is surgery useful in very old patients with intracranial meningioma?
PMID- 9652618
TI - Pilocarpine as an adjuvant to morphine therapy.
PMID- 9652620
TI - Acarbose-induced hepatic injury.
PMID- 9652619
TI - Epidemic ciprofloxacin-resistant Salmonella typhi in Tajikistan.
PMID- 9652621
TI - Injection of GABA-agonist into globus pallidus in patient with Parkinson's
disease.
PMID- 9652622
TI - Chlamydia trachomatis detection and the menstrual cycle.
PMID- 9652623
TI - Subcapsular liver haematomas caused by bar ends in mountain-bike crashes.
PMID- 9652624
TI - Gro Harlem Brundtland secures top job at WHO.
PMID- 9652625
TI - US Public Health Service sets out plan for xenotransplantation.
PMID- 9652626
TI - Sorting out the true from the false.
PMID- 9652627
TI - Vector problems still thwart gene-therapy promise.
PMID- 9652628
TI - Rebuilding the UK welfare state.
PMID- 9652629
TI - 25 years later, US abortion war still drags on.
PMID- 9652630
TI - Danish HIV-1 puzzle solved.
PMID- 9652631
TI - Child claim over hazards of silicone breast implant planned in UK.
PMID- 9652632
TI - Canadian hopes for low-cost drugs dashed.
PMID- 9652633
TI - Hepatitis C.
PMID- 9652634
TI - Impact of anti-vaccine movements on pertussis control: the untold story.
AB - To assess the impact of anti-vaccine movements that targeted pertussis whole-cell
vaccines, we compared pertussis incidence in countries where high coverage with
diphtheria-tetanus-pertussis vaccines (DTP) was maintained (Hungary, the former
East Germany, Poland, and the USA) with countries where immunisation was
disrupted by anti-vaccine movements (Sweden, Japan, UK, The Russian Federation,
Ireland, Italy, the former West Germany, and Australia). Pertussis incidence was
10 to 100 times lower in countries where high vaccine coverage was maintained
than in countries where immunisation programs were compromised by anti-vaccine
movements. Comparisons of neighbouring countries with high and low vaccine
coverage further underscore the efficacy of these vaccines. Given the safety and
cost-effectiveness of whole-cell pertussis vaccines, our study shows that, far
from being obsolete, these vaccines continue to have an important role in global
immunisation.
PMID- 9652635
TI - More than a green placebo.
PMID- 9652636
TI - Meta-analysis of homoeopathy trials.
PMID- 9652637
TI - Meta-analysis of homoeopathy trials.
PMID- 9652638
TI - Meta-analysis of homoeopathy trials.
PMID- 9652639
TI - Meta-analysis of homoeopathy trials.
PMID- 9652640
TI - Meta-analysis of homoeopathy trials.
PMID- 9652641
TI - Meta-analysis of homoeopathy trials.
PMID- 9652642
TI - Meta-analysis of homoeopathy trials.
PMID- 9652643
TI - Meta-analysis of homoeopathy trials.
PMID- 9652644
TI - Inhaled sodium cromoglycate in young children with moderate asthma.
PMID- 9652645
TI - Inhaled sodium cromoglycate in young children with moderate asthma.
PMID- 9652646
TI - Granulocyte-colony-stimulating factor in diabetic foot infection.
PMID- 9652647
TI - Left-ventricular dysfunction.
PMID- 9652648
TI - Left-ventricular dysfunction.
PMID- 9652649
TI - Diagnosis of fever in Africa.
PMID- 9652650
TI - Diagnosis of fever in Africa.
PMID- 9652651
TI - Regional node radiotherapy for breast cancer.
PMID- 9652652
TI - Refutation of investigation commissioned by Karolinska Institute.
PMID- 9652653
TI - Reducing disability among the elderly in Europe.
PMID- 9652654
TI - Reducing disability among the elderly in Europe.
PMID- 9652655
TI - False-positive self-reports of HIV-1 infection.
PMID- 9652656
TI - Half-life of truth in medicine.
PMID- 9652657
TI - The name of the dose.
PMID- 9652658
TI - AIDS, the unbridgable gap.
PMID- 9652659
TI - Can we really grow new blood vessels?
PMID- 9652660
TI - When can an exacerbation of COPD be treated at home?
PMID- 9652661
TI - Beta-endorphin in the immune system--mediator of pain and stress?
PMID- 9652662
TI - What lessons can be learnt from withdrawal of mibefradil from the market?
PMID- 9652663
TI - Treatment options in severe aplastic anaemia.
PMID- 9652664
TI - Implications of European directive on medical devices.
PMID- 9652665
TI - Outlook for sexually transmitted diseases.
PMID- 9652666
TI - Spectrum of AIDS-associated malignant disorders.
AB - BACKGROUND: To clarify which types of cancer result from AIDS, we compared the
cancer experiences of people with AIDS with those of the general population by
matching population-based cancer and AIDS registries in the USA and Puerto Rico.
METHODS: We used a probabilistic matching algorithm to compare names, birth
dates, and, where available, social-security numbers of 98,336 people with AIDS
and 1,125,098 people with cancer aged less than 70 years. We defined AIDS-related
cancers as those with both significantly raised incidence post-AIDS and
increasing prevalence from 5 years pre-AIDS to 2 years post-AIDS. FINDINGS: Among
people with AIDS, we found 7028 cases of Kaposi's sarcoma (KS), 1793 of non
Hodgkin lymphoma (NHL), and 712 other cases of histologically defined cancer.
Incidence rates among people with AIDS were increased 310-fold for KS, 113-fold
for NHL, and 1.9-fold (95% CI 1.5-2.3) for other cancers. Of 38 malignant
disorders other than KS and NHL, only angiosarcoma (36.7-fold), Hodgkin's disease
(7.6-fold), multiple myeloma (4.5-fold), brain cancer (3.5-fold), and seminoma
(2.9-fold) were raised and increasing significantly (p<0.02) from the pre-AIDS to
the post-AIDS period. INTERPRETATION: Interpretation is complicated by screening
and shared risk factors, such as sexual behaviour and cigarette smoking. However,
our data indicate that AIDS leads to a significantly increased risk of Hodgkin's
disease, multiple myeloma, brain cancer, and seminoma. Immunological failure to
control herpes or other viral infections may contribute to these malignant
diseases.
PMID- 9652667
TI - Smoking and risk of dementia and Alzheimer's disease in a population-based cohort
study: the Rotterdam Study.
AB - BACKGROUND: Previous studies suggested a protective effect of smoking on
Alzheimer's disease, but most were case-control studies based on prevalent cases.
The findings of prospective studies on the association between smoking and the
risk of dementia are inconclusive. METHODS: We did a population-based follow-up
study of elderly people who were initially free of dementia. 6870 people aged 55
years and older agreed to take part. Smoking history was taken at baseline and
participants were classified as never smokers, former smokers, and current
smokers. During follow-up, we recorded all incident cases of dementia. We used
never smokers as the reference category to calculate relative risks of dementia
and Alzheimer's disease by Cox proportional hazards regression, after adjustment
for age, sex, education, and alcohol intake. We also examined modification of
risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean
follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were
detected, of which 105 were Alzheimer's disease. Compared with never smokers,
smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6])
and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for
Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5
14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]).
INTERPRETATION: Smoking was associated with a doubling of the risk of dementia
and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no
increased risk of dementia suggests an interaction between smoking and the
APOEepsilon4 genotype in the aetiology of Alzheimer's disease.
PMID- 9652668
TI - Extended excretion of rotavirus after severe diarrhoea in young children.
AB - BACKGROUND: Rotaviruses are the major cause of severe childhood diarrhoea.
Knowledge of the natural history of infection, including duration of intestinal
virus shedding, is important in the understanding of transmission, sources of
infection, and immune responses. METHODS: We carried out a study of rotavirus
excretion in 37 children admitted to hospital with severe rotavirus diarrhoea.
Sequential faecal specimens were collected from each child during 100 days of
surveillance, and screened for rotavirus by EIA and by amplification of genome
double-stranded RNA by reverse-transcription PCR. IgA coproantibody was estimated
by EIA. FINDINGS: Duration of rotavirus excretion ranged from 4 to 57 days after
onset of diarrhoea. Excretion ceased within 10 days in 16 (43%) children, and
within 20 days in 26 (70%) children. Extended excretion was detected for 25-57
days in the remaining 11 (30%) children owing mainly to continued excretion of
the primary infecting strain. Extended excretion was significantly associated
with antirotavirus IgA coproantibody boosts during 100 days of surveillance
(p=0.001, log-rank test), and with recurrence of mild diarrhoea symptoms during
convalescence (p=0.006, Fisher's exact test). INTERPRETATION: Severe rotavirus
disease in young children may be followed by extended excretion of rotavirus. The
risk of transmission to others may be greater than previously believed. Extended
excretion could also explain some cases of the postgastroenteritis syndrome.
PMID- 9652669
TI - Metabolic abnormalities in developmental dyslexia detected by 1H magnetic
resonance spectroscopy.
AB - BACKGROUND: Neurological and physiological deficits have been reported in the
brain in developmental dyslexia. The temporoparietal cortex has been directly
implicated in dyslexic dysfunction, and substantial indirect evidence suggests
that the cerebellum is also implicated. We wanted to find out whether the
neurological and physiological deficits manifested as biochemical changes in the
brain. METHODS: We obtained localised proton magnetic resonance spectra
bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined
dyslexic men and 15 control men of similar age. FINDINGS: We found biochemical
differences between dyslexic men and controls in the left temporo-parietal lobe
(ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or
=0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or
=0.05; (not significant). We found lateral biochemical differences in dyslexic
men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right,
p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such
lateral differences in controls. There was no significant relation between the
degree of contralateral chemical difference and handedness in dyslexic or control
men. INTERPRETATION: We suggest that the observed differences reflect changes in
cell density in the temporo-parietal lobe in developmental dyslexia and that the
altered cerebral structural symmetry in dyslexia is associated with abnormal
development of cells or intracellular connections or both. The cerebellum is
biochemically asymmetric in dyslexic men, indicating altered development of this
organ. These differences provide direct evidence of the involvement of the
cerebellum in dyslexic dysfunction.
PMID- 9652670
TI - Home treatment of exacerbations of chronic obstructive pulmonary disease by an
acute respiratory assessment service.
AB - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease are a major
cause of hospital admissions, but do not require intensive investigation or
complex therapy. We investigated the suitability of home care for severe
uncomplicated exacerbations. METHODS: Over 3.5 years we assessed 962 patients
with exacerbations of chronic obstructive pulmonary disease after referral to a
hospital respiratory department by their family physicians. All patients had
chest radiographs, oxygen-saturation or arterial-gas analysis, spirometry, and
physical assessment. Unless admission was thought to be essential, patients were
allowed home with a customised treatment package. Each patient was visited daily
by a respiratory nurse who monitored progress and treatment compliance and
provided education and reassurance. FINDINGS: 145 (15%) of 962 required admission
at initial referral and 115 (12%) were admitted later. 653 (68%) patients were
managed entirely at home and 49 (5%) were referred inappropriately. One patient
died at home. All patients had severe disease with a mean forced expiratory
volume in 1 s of 1.02 L and 395 (41%) had required hospital admission in the
previous year. INTERPRETATION: After formal assessment in a hospital respiratory
unit, many patients with exacerbations of chronic obstructive pulmonary disease
can be treated at home by respiratory nurses.
PMID- 9652671
TI - A rash, circulating anticoagulant, then meningitis.
PMID- 9652672
TI - Resting blood pressure increase during exposure to a radio-frequency
electromagnetic field.
PMID- 9652673
TI - Alternative hypothesis for efficacy of macrolides in acute coronary syndromes.
PMID- 9652674
TI - Fetal swallowing of IgE.
PMID- 9652675
TI - Can class I epitope of M protein be a diagnostic marker for rheumatic fever in
populations endemic for group A streptococci?
PMID- 9652677
TI - Cystamine bislactamide: a cosmetic allergen.
PMID- 9652676
TI - Oxindole in pathogenesis of hepatic encephalopathy.
PMID- 9652678
TI - Mesozoic neoplasia: origins of haemangioma in the Jurassic age.
PMID- 9652679
TI - UN adopts plans to combat worldwide illicit drug use.
PMID- 9652680
TI - COX provides missing link in mechanism of aspirin in colon cancer.
PMID- 9652681
TI - Sorting the hype from the facts in melanoma.
PMID- 9652682
TI - Uzbek health care--no longer back in the USSR.
PMID- 9652683
TI - Leaked document indicates Canada's future stance on human research.
PMID- 9652684
TI - Spain celebrates leading the world in organ donation.
PMID- 9652685
TI - Acne vulgaris.
PMID- 9652686
TI - The voice of the castrato.
PMID- 9652687
TI - Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy,
hyperlipidaemia, and insulin resistance.
AB - HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral
lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia,
and insulin resistance. The catalytic region of HIV-1 protease, to which protease
inhibitors bind, has approximately 60% homology to regions within two proteins
that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1
(CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We
hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome
P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the
retinoid X receptor; and peroxisome proliferator activated receptor type gamma
(PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral
adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would
impair hepatic chylomicron uptake and triglyceride clearance by the endothelial
LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to
central fat deposition (and in the breasts in the presence of oestrogen), insulin
resistance, and, in susceptible individuals, type 2 diabetes. Understanding the
syndrome's pathogenesis should lead to treatment strategies and to the design of
protease inhibitors that do not cause this syndrome.
PMID- 9652688
TI - Dissection of regional lymph nodes in cutaneous melanoma.
PMID- 9652689
TI - Dissection of regional lymph nodes in cutaneous melanoma.
PMID- 9652690
TI - Dissection of regional lymph nodes in cutaneous melanoma.
PMID- 9652691
TI - Vein compliance for preoperative assessment in vascular bypass surgery.
PMID- 9652692
TI - Chimerism in scleroderma.
PMID- 9652693
TI - Chimerism in scleroderma.
PMID- 9652694
TI - Stopping the Breast Cancer Prevention Trial.
PMID- 9652695
TI - Mortality of hepatitis A in adults with hepatitis C antibodies.
PMID- 9652696
TI - MRSA and minimally invasive treatments for benign prostatic hypertrophy.
PMID- 9652697
TI - Postoperative cognitive dysfunction in the elderly.
PMID- 9652698
TI - Postoperative cognitive dysfunction in the elderly.
PMID- 9652699
TI - Safety guidelines for exercise during pregnancy.
PMID- 9652700
TI - Fluticasone propionate for chronic obstructive pulmonary disease.
PMID- 9652701
TI - A selective policy in follow-up for bowel cancer.
PMID- 9652702
TI - A selective policy in follow-up for bowel cancer.
PMID- 9652703
TI - First-ever stroke incidence.
PMID- 9652704
TI - Medical advocacy for the oppressed.
PMID- 9652705
TI - Medical advocacy for the oppressed.
PMID- 9652706
TI - Medical advocacy for the oppressed.
PMID- 9652707
TI - Screening for HIV-1 in pregnancy.
PMID- 9652708
TI - Clinical experience of UK medical students.
PMID- 9652709
TI - Israel's ban on Ethiopians' blood.
PMID- 9652710
TI - On being a ginseng connoisseur.
PMID- 9652711
TI - Global epidemiology of sexually transmitted diseases.
PMID- 9652712
TI - Sexually transmitted diseases enhance HIV transmission: no longer a hypothesis.
PMID- 9652713
TI - The epidemiology of global antibiotic resistance among Neisseria gonorrhoeae and
Haemophilus ducreyi.
PMID- 9652714
TI - Update on sexually transmitted mycoplasmas.
PMID- 9652715
TI - Genital herpes--how much of a public-health problem?
PMID- 9652716
TI - Is elimination of endemic syphilis transmission a realistic goal for the USA?
PMID- 9652717
TI - Is vaccination against human papillomavirus a possibility?
PMID- 9652718
TI - Programmes to reduce pelvic inflammatory disease--the Swedish experience.
PMID- 9652719
TI - Advances in control of sexually transmitted diseases in developing countries.
PMID- 9652720
TI - Do we know the effectiveness of behavioural interventions?
PMID- 9652721
TI - Primary and secondary syphilis--United States, 1997.
AB - Syphilis is an acute and chronic sexually transmitted disease (STD) caused by
infection with Treponema pallidum. The disease is characterized by skin and
mucous membrane lesions in the acute phase (primary and secondary [P&S] syphilis)
and lesions of the bone, viscera, and cardiovascular and neurologic systems in
the chronic phase. Because syphilis enhances transmission of human
immunodeficiency virus (HIV), prevention of syphilis is important for controlling
HIV. During 1986-1990, an epidemic of syphilis occurred throughout the United
States. Syphilis rates began to decline in 1991 and have declined each year since
that time. To determine whether this decline is reflected in changes in the
epidemiology of syphilis, CDC analyzed notifiable disease surveillance data for
1997. This report summarizes the findings of the analysis, which indicate that
8551 cases of primary and secondary (P&S) syphilis were reported in 1997, an 83%
decline in cases from the peak of the epidemic in 1990, and that syphilis remains
substantially more common in non-Hispanic blacks than in other racial/ethnic
groups and continues to be concentrated in the Southern region of the United
States [corrected].
PMID- 9652722
TI - State-specific pregnancy rates among adolescents--United States, 1992-1995.
AB - In the United States during 1985-1990, the pregnancy rate for persons aged 15-19
years increased 9%. From 1991 to 1992, however, the rate declined substantially
in 31 of the 42 states for which data were available; from 1992 through 1995, the
birth rate declined steadily, and state-specific abortion rates decreased
annually. This report presents estimated state-specific pregnancy rates for 1992
1995 for adolescents aged < or =19 years by age and race and the percentage
change in state-specific pregnancy rates for persons aged 15-19 years for 1992 to
1995. The findings indicate a downward trend in pregnancy rates for persons aged
15-19 years during 1992-1995 for all 43 states for which data were available.
PMID- 9652723
TI - Progress toward poliomyelitis eradication--Europe and Central Asian Republics,
1997-May 1998.
AB - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
by 2000. In 1995, the World Health Organization (WHO) European Region (EUR),
comprising 51 member states (including Israel and the Central Asian Republics),
accelerated efforts toward polio eradication. Improvements in status have been
reported previously. This report summarizes progress toward polio eradication
during 1997-1998, demonstrating that polio incidence has decreased to seven cases
in 1997 and two cases in 1998, and surveillance has improved substantially.
PMID- 9652724
TI - Receptor-Ck and leukemogenesis.
PMID- 9652725
TI - Expression of cyclin D1 in mouse B cell lymphomas of different histologic types
and differentiation stages.
AB - The G1 cyclin, cyclin D1, has been implicated in the development of human and
mouse tumors. Here we describe immunohistochemical analyses of cyclin D1 for a
large panel of mouse B cell tumors. In addition, we characterize cyclin D1
expression in a series of cultured cell lines that represent transformed B cells
at different stages of development. Immunohistochemical analysis showed that for
low-grade lymphomas, cyclin D1 was expressed by 83% of centroblastic centrocytic
(CBCC) and 14% of small lymphocytic lymphomas (SLL). For high-grade tumors, 28%
of B lymphoblastic and 23% of centroblastic tumors expressed cyclin D1, while all
immunoblastic lymphomas were negative. Studies of RNA and protein prepared from
cultured B lineage tumors showed that cyclin D1 was expressed by all pre-B and
most B cell tumors but not by cell lines representative of late B cell
differentiation or by plasma cells. Expression of cyclin D1 in the lymphomas was
not associated with alterations in the genomic structure of the Fis-1 (Bcl-1)
common proviral integration site or cyclin D1 itself or with cell growth activity
as assessed by expression of proliferating cell nuclear antigen (PCNA).
PMID- 9652726
TI - Induction of differentiation and apoptosis by dithizone in human myeloid leukemia
cell lines.
AB - We investigated the effect of diphenylthiocarbazone (dithizone) and its
structurally related compounds on the differentiation and apoptosis of two human
myeloid leukemia cell lines. Dithizone caused a time- and concentration-dependent
induction of differentiation in both the promyelocytic leukemia cell line HL-60
cells and the myeloblastic leukemia cell line ML-1 cells, as measured by
nitroblue tetrazolium (NBT) reducing activity. Morphological changes and esterase
activities confirmed that this differentiation took place. The induction of
differentiation required the addition of dithizone to the culture medium for at
least 12 h. The differentiation inducing activity was inhibited by the
preincubation of dithizone with various metal ions such as Pb2+, Zn2+, Cu2+ and
Mn2+ ions, but not with Fe3+ and Mg2+ ions. In addition, the DNA extracted from
dithizone-treated HL-60 cells showed a typical ladder pattern characteristic of
apoptosis in agarose gel electrophoresis. A quantitative analysis of DNA
fragmentation revealed that this apoptosis was concentration- and time-dependent
in both the HL-60 and ML-1 cells. Dithizone-induced apoptosis was also inhibited
by preincubation with Mn2+ ions, but not with Mg2+ ions. These results indicate
that dithizone induces both differentiation and apoptosis in HL-60 and ML-1 cells
through a unique mechanism including metal chelation.
PMID- 9652727
TI - Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced
hematopoietic differentiation with a defective retinoblastoma tumor suppressor
mediated pathway.
AB - The retinoblastoma tumor suppressor (Rb) gene product plays an essential role in
cell-cycle regulation. However, its role in terminal differentiation of
hematopoietic cells is speculative. Here we show a model of 12-o
tetradecanoylphorbol-13-acetate (TPA)-induced hematopoietic differentiation and
growth arrest with a defective Rb-mediated pathway. TPA treatment arrested the
cell cycle of a human hematopoietic cell line, MEG-01s, at the G1-S boundary and
induced expression of p21/SDI1/WAF1/CIP1 and p27/KIP1. Both of these proteins
were present in cyclin E-associated complexes, the histone H1 and Rb kinase
activities of which were then inactivated. However, MEG-01s cells lacked the
intact Rb protein and the Rb-mediated pathway was defective. This model raises a
question about the role for Rb in terminal differentiation of hematopoietic
cells.
PMID- 9652728
TI - Protection of leukemic cells by deoxycytidine: in vitro measures of protection
against cytosine arabinoside.
AB - Plasma deoxycytidine levels can be very high in leukemia patients. Such levels
strongly protected leukemia cell lines against cytosine arabinoside (araC),
fludarabine and 2-chlorodeoxyadenosine when using clonogenic survival as the
endpoint. This endpoint is not easily used when studying protection in clinical
leukemia cell samples. Therefore, we tested other ways to quantify protection
based on biochemical measures of viability or drug metabolism. The estimates of
the strength of protection based on rates of DNA synthesis, cellular araC uptake
and incorporation of araC into DNA were much lower than the estimates using
clonogenic survival. The MTT viability assay gave excellent estimates and appears
promising for studying protection in primary leukemia cell samples.
PMID- 9652729
TI - Cytokine gene activity in AML cells in vivo in patients.
AB - The proliferation of acute myelogenous leukemia cells is dependent upon cytokine
stimulation. Additionally, there is a body of literature which reports that
leukemia cells produce GMCSF, IL6, and other cytokines. The study reported here,
using an rt-multiplex polymerase method, determined the presence or absence of
transcripts in freshly obtained AML cells for the following cytokine or cytokine
related genes: IL 1beta, IL1ra, TNF alpha, GMCSF, IL6, flt 3, and hSCF. This
demonstrated that leukemia cell populations usually contain transcripts for
IL1beta, TNF alpha, flt 3 and flt 3 ligand in vivo and that transcripts for the
other cytokines only appear after the leukemia cells are processed in vitro. The
presence of TNF alpha transcripts appears to be associated with resistance to
remission induction therapy. Furthermore, the transcript profile of the leukemia
cells can change during remission induction therapy. The data also demonstrate
the assessment of cytokine production by leukemia cells after in vitro
manipulation should not be extrapolated to the in vivo situation.
PMID- 9652730
TI - Flow cytometric assessment of three different methods for the measurement of in
vitro apoptosis.
AB - Chlorambucil-induced apoptosis was assessed by three different flow cytometric
methods in B-cell chronic lymphocytic leukaemia (B-CLL) cells cultured in vitro
and the results were compared with those derived from the morphological
assessment of the same samples. Spontaneous apoptosis was consistently observed
in the control cultures in the absence of drug but this accounted for less than
12% of all cells in every case. The methods under investigation were the Annexin
V labelling assay, the terminal deoxynucleotidyl transferase (TdT) end-labelling
assay and the labelling of a 38 kDa mitochondrial membrane protein (7A6 antigen)
which is exposed on cells undergoing apoptotic cell death (Apo2.7 assay). The
Annexin V assay consistently stained a higher percentage of cells and with a
greater separation between the positive and negative cell populations. We
conclude that the phosphatidyl serine translocation to the outer leaflet of the
cell membrane following an apoptotic signal, as labelled by Annexin V, probably
occurs before the development of the DNA strand breaks or the exposure of 7A6
antigen in those cells triggered to die by apoptosis.
PMID- 9652731
TI - Tobacco, alcohol, diet and risk of non-Hodgkin's lymphoma: a case-control study
in Uruguay.
AB - To test whether high meat intake is associated with the development of non
Hodgkin lymphoma (NHL) in the Uruguayan population, a case-control study was
performed at the Instituto Nacional de Oncologia, Montevideo, Uruguay. After
controlling for age, sex, residence, education, urban/rural status and the habit
of drinking the beverage 'mate', red meat intake was associated with an increased
risk of NHL of 2.5. This finding was similar in both sexes separately. Odds
ratios (OR) for the highest tertile of barbecued meat was 1.7 among men, whereas
salted meat was associated with an increased risk of NHL (OR 4.9, 95% CI 1.4
17.7). The effect of processed and salted meat among women was of much less
magnitude and the OR's were non-significant. Also, cumulative exposure to 'mate'
drinking displayed an OR of 2.4 (95% CI 1.0-5.6). Smokers of black tobacco and
hand-rolled cigarettes were associated with an increased risk of 3.5 (95% 1.1
10.9), whereas beer drinkers showed an increased OR of 5.5 (95% 1.1-26.7) in men.
It could be concluded that red or salted meat intake, smoking of black tobacco,
and beer and 'mate' drinking are risk factors for NHL in the Uruguayan
population.
PMID- 9652732
TI - Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical
analysis of 117 cases.
AB - To gain more insight into the understanding of myelodysplastic syndromes (MDS) as
they occur in Thailand, a retrospective clinicopathologic analysis was conducted
in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996
at the five major medical centers in various geographic regions of the country.
The central reviewers independently examined the bone marrow and peripheral blood
smears of all the patients and classify the disease according to the French
British-American (FAB) classification. There were a total of 117 eligible
patients. The median age of the patients was 56 years (range 16-86). The
male:female ratio was 1:1. Thirty-two percent of the patients were younger than
40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML,
9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of
the patients. In the 34 patients in whom the cytogenetics in the bone marrow were
analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were
the most common aberration, each being detected in 26.7% of the patients.
Transfusions were the main therapeutic modality in 80% of the patients. Kaplan
Meier analysis revealed a 5 year survival rate of 29% for the whole group with a
median survival of 24 months. Twenty-five percent of the patients had progressed
to acute myelogenous leukemia (AML) with a median time to disease-progression of
23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4,
19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression
analysis revealed the percentage of blasts in the bone marrow as the only
parameter significantly associated with survival and disease progression. On
comparison with data from other countries, the age of Thai patients with MDS is
considerably lower than the western population but is comparable to other asian
countries. The distribution of the FAB subtypes and the survival of the patients
are similar. The major prognostic features, however, lie in the percentage of
blasts in the bone marrow rather than the degree of the observed cytopenia.
PMID- 9652733
TI - Lack of TEL/AML1 fusion in pediatric AML: further evidence for lineage
specificity of TEL/AML1.
AB - BACKGROUND: The TEL/AML1 fusion associated with t(12;21)(p13;q22) is the most
common gene rearrangement in childhood malignancy, occurring in approximately 25%
of pediatric acute lymphoblastic leukemia. The TEL/AML1 rearrangement is cryptic
at the cytogenetic level but confers a favorable prognosis. The AML1 gene was
first identified by virtue of its involvement in adult and pediatric acute
myeloid malignancies associated with t(8;21) and t(3;21)(q26;q22.1). We have
therefore determined the frequency of the TEL/AML1 fusion in pediatric myeloid
leukemias by RT-PCR analysis. METHODS: Total RNA was isolated from cryopreserved
bone marrow samples of 38 pediatric patients with AML. RNA quality was controlled
for by amplification of the TEL gene. An RT-PCR assay was then used to test for
the presence of the TEL/AML1 fusion. RESULTS: 29 patients had adequate RNA for
analysis. Zero out of 29 pediatric AML patients had evidence for the TEL/AML1
fusion by RT-PCR. CONCLUSIONS: The TEL/AML1 fusion does not occur in children
with AML and suggests that the TEL/AML1 rearrangement is restricted in pediatric
hematologic malignancy to B lineage ALL.
PMID- 9652735
TI - Fournier's gangrene as first presentation of promyelocytic leukemia.
AB - A 50-year-old male is described who presented with Fournier's gangrene as what is
probably the first manifestation of a newly diagnosed acute myelogenous leukemia
(AML), promyelocytic type or variant type M3 according to the FAB classification.
Despite aggressive fluid resuscitation, tuned infusion of vasoactive drugs,
appropriate antibiotics and extensive surgical debridement, the patient died
within 24 h as a result of irreversible septic shock.
PMID- 9652734
TI - Acute myelogenous leukemia in Down's syndrome: report of a single pediatric
institution using a BFM treatment strategy.
AB - Between July 1990 and December 1995, 111 new consecutive pediatric patients with
acute myelogenous leukemia (AML) have been treated in our institution. Eleven of
them (9.9%) had Down's syndrome (DS), 6 boys and 5 girls. The median age was 22.5
(range 10-40) months. FAB subtypes were the following: M7: 6, M4: 3, and M0: 2.
Five of them had previously had myelodysplasia and in 3, all FAB M7,
myelofibrosis was detected. This population was treated with two consecutive
protocols. Nine patients were included in the AML-HPG-90 protocol and 2 patients
in the AML-HPG-95 study, respectively. However, all DS patients in this series
received the same treatment. Eight patients achieved complete remission: two
patients received two cycles of intensification with high dose (HD) ara-C, and 1
patient, only one cycle; the other 5 were prevented from receiving such therapy
because of unacceptable toxicity or death. At 45 months, event-free survival and
overall survival estimates were 0.30, S.E. 0.16. Mortality was remarkably high.
All deaths (7) were associated with sepsis (5) or pulmonary infection (2). Three
deaths occurred before achieving complete remission, 3 patients died during the
consolidation phase and 1 died whilst off treatment. No one presented leukemic
relapse. We conclude that this AML-BFM treatment strategy is highly toxic to
children with DS and AML in our setting. Efforts will be made to improve clinical
support and to administer less intensive therapy to this particular pediatric AML
subgroup, which, in fact, has a better prognosis than the same non-trisomic
population.
PMID- 9652736
TI - Functional interplay between p53 and E2F through co-activator p300.
AB - Both E2F and p53 are sequence specific transcription factors that regulate early
cell cycle progression. The pathway of control mediated through E2F governs the
transition from G1 into S phase whereas p53 in response to genotoxic stress can
facilitate cell cycle arrest or apoptosis. The mechanisms which influence the
outcome of p53 induction are not clear, although transcription of the p53 target
gene, encoding the cdk-inhibitor p21(Waf1/Cip1), correlates with p53-mediated
cell cycle arrest. Here using a combination of biochemical and functional assays
we identify p300 as a co-activator required for p53-dependent transcriptional
activation of Waf1/Cip1. Furthermore, we show that the cdk-inhibitor
p21(Waf1/Cip1) autoregulates in a positive fashion transcription through
modulating the activity of the p53/p300 complex, whilst negatively regulating the
activity of E2F by preventing cdk-dependent phosphorylation of pRb. Consistent
with a role for p21(Waf1/Cip1) in the autoregulation of p53-dependent
transcription, p300 augments the ability of p53 to cause G1 arrest and,
conversely, cells undergoing p53-dependent apoptosis are rescued by p300. Thus,
our data suggest that the ability of p300 to interact with p53 influences the
physiological consequence of p53 activation. From previous studies it is known
that cells expressing aberrant levels of E2F-1 can undergo p53-dependent
apoptosis. In addition, we find that E2F-1 can cause apoptosis in p53-/- tumour
cells and further p300, which also functions as a co-activator for the E2F/DP
heterodimer, enhances the apoptotic activity of E2F-1. In conditions where E2F-1
and p53 co-operate in apoptosis E2F-1 can effectively compete for p300, causing a
reduction in p53-dependent transcription. Thus, a functional interaction between
p300 and either p53 or E2F-1 has a profound impact on early cell cycle
progression, specifically in regulating the contrasting outcomes of cell cycle
arrest and apoptosis. These results suggest a critical role for p300 in
integrating and co-ordinating the functional interplay between the pathways of
growth control mediated by E2F and p53.
PMID- 9652738
TI - Hypomethylation and increased gene expression of p16INK4a in primary and
metastatic breast carcinoma as compared to normal breast tissue.
AB - Controversy continues to surround the role of p16INK4a in cell cycle control and
carcinogenesis. Mutations, deletions and changes in methylation patterns of
p16INK4a have been proposed as mechanisms leading to abnormal expression of the
gene. We show here that primary and metastatic breast carcinomas demonstrate
hypomethylation of p16INK4a which is associated with expression of p16INK4a mRNA,
as compared to normal breast tissue which demonstrates a relative
hypermethylation of p16INK4a associated with the absence of p16INK4a expression.
These data suggest that methylation and lack of expression of p16INK4a is not a
central mechanism in the development of breast carcinoma, but rather that the
gene is functioning and expressed in breast carcinoma more frequently than in
normal breast tissue. The role of p16INK4a is much more complex than has been
previously hypothesized.
PMID- 9652737
TI - Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB
transactivation and suppresses anchorage independent growth of HPV immortalized
human keratinocytes.
AB - AP-1 transactivation appears to be required for mouse JB6 cell neoplastic
transformation induced by the tumor promoter TPA or epidermal growth factor
(EGF). Exposure to AP-1 transrepressing retinoids and glucocorticoids and
expression of a dominant negative c-jun (TAM67) blocked tumor promoter-induced AP
1 transactivation and neoplastic transformation. The aim of the present study was
to extend the inquiry of the role of AP-1 and other transcription factors to
human neoplastic progression. Expression of human papillomavirus (HPV) 16 or 18
E6 and E7 immortalizes human keratinocytes and inhibits serum/calcium-stimulated
differentiation. Further transformation by v-fos co-expression renders these
keratinocytes tumorigenic in nude mice. We have analysed two series of E6/E7
immortalized human keratinocyte cell lines that show progressing phenotypes
ranging from differentiation sensitive to anchorage-independent to tumorigenic in
nude mice. We analysed the activities of AP-1 and NF-kappaB which may 'cross
talk'. Both DNA binding and transactivation of AP-1 and NF-kappaB transcription
factors showed elevation in the anchorage-independent (16RH) and tumorigenic (18
v-fos) keratinocyte lines compared to the less progressed but immortalized cell
lines. HPV E7 was expressed at a constant level shown by quantitative RT-PCR in
both the more and the less progressed lines, indicating that E7 is not the factor
limiting this progression. Blocked shift/supershift analysis indicates that Fos
family member proteins especially Fra-1 and Fra-2 are related to progression and
no changes found in the Jun family member proteins although they are present in
the AP-1/DNA binding complex. When a dominant negative mutant c-jun driven by a
human keratin 14 promoter was co-transfected with AP-1 or NF-kappaB reporters,
both AP-1 and NF-kappaB activities were suppressed in the more progressed cell
lines 16RH and 18 v-fos but not in the less progressed 16RL or 18 cell lines.
Overexpression of the same dominant negative c-jun did not inhibit p53 dependent
reporter transactivation, indicating the specificity of inhibition of AP-1 and NF
kappaB transactivation in the HPV-immortalized cells. Stable transfectants of
this mutant c-jun in the two more progressed cell lines 16RH and 18 v-fos showed
reduced AP-1 and NF-kappaB activation and reduced anchorage-independent growth.
Together, these results indicate that activation of AP-1, NF-kappaB or both may
contribute to neoplastic progression in HPV immortalized human keratinocytes and
that specific targeting of the elevated levels seen in benign or malignant tumors
might be effective for prevention or treatment of human cancer.
PMID- 9652739
TI - Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25
dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1
phase.
AB - Drug resistance that occurs during cancer chemotherapy has been a major problem
in controlling neoplastic progression. To study the cellular mechanisms of
acquired drug resistance we developed 1,25-dihydroxyvitamin D3 (1,25D3)-resistant
sublines of promyelocytic leukemia HL60 cells which have increased proliferation
rates (Exp. Cell Res., 224, 312, 1996; Cancer Res., 50, 5513, 1996). We report
here that the resistant sublines display varying degrees of shortening of the G1
phase as compared to the parental HL60-G cells. Protein levels of cyclins E, D1,
D2 and D3 are elevated in these resistant cell lines, and cyclin D1 is especially
high in 40AF cells, which has the shortest G1 length. The protein levels of
cyclin-dependent kinase (Cdk)2, Cdk4 and Cdk6 are not altered in the resistant
sublines. Both Cdk2 and Cdk6-associated kinase activites are increased in the
resistant sublines, but not Cdk4 kinase activity. Protein levels of p27Kip1 are
not consistently altered in the resistant sublines as compared to the parental
HL60-G cells, but are reduced relative to HL60-G cells arrested by 96 h treatment
with 1,25D3. Interestingly, the resistant cell lines constitutively express high
levels of retinoblastoma protein (pRb), and pRb is highly phosphorylated,
indicating that the G1 cyclin/Cdk complexes in the resistant cells are
physiologically active. The results suggest that the increased activity of cyclin
D/Cdk6, and perhaps cyclin E/Cdk2, lead to rapid hyperphosphorylation of pRb and
consequently a shorter early G1 phase, and that in the resistant cells the
increased ratio of cyclin E to p27Kip1 results in activation of Cdk2 and
contributes to the abrogation of the 1,25D3-induced block to the S phase entry.
Additionally, it is apparent that constitutively increased levels of pRb are
compatible with increased rates of cell proliferation.
PMID- 9652740
TI - The BPV-4 co-carcinogen quercetin induces cell cycle arrest and up-regulates
transcription from the LCR of BPV-4.
AB - Bracken fern is the environmental co-carcinogen of BPV-4 in the induction of
neoplasias of the upper alimentary canal of cattle. The flavonoid quercetin is
one of the most potent and best characterised mutagens present in the fern. We
have shown that transfection with BPV-4 DNA and exposure to a single dose of
quercetin leads to tumorigenic transformation of primary bovine cells. We now
show that quercetin induces cell cycle arrest and up-regulates transcription from
the BPV-4 long control region (LCR). This up-regulation is mediated by a 21
nucleotide-long cis-element in the LCR, designated QRE-1, which is located
immediately downstream of the TATA box. Cellular proteins bind to QRE-1 and
removal or substitution of QRE-1 lead to the abrogation of the response to
quercetin. As expression of the viral oncogenes is controlled by the LCR,
perturbation in this control and increased oncoprotein expression are likely to
contribute to fully malignant cell transformation by overcoming the cell cycle
arrest induced by quercetin, thus forcing damaged cells to proliferate.
PMID- 9652741
TI - Allelic loss analysis of gamma-ray-induced mouse thymic lymphomas: two candidate
tumor suppressor gene loci on chromosomes 12 and 16.
AB - A total of 429 gamma-ray-induced thymic lymphomas were obtained from F1 and
backcross mice between BALB/c and MSM strains, about a half of which carried a
p53-deficient allele. A genome-wide allelic loss analysis has revealed two loci
exhibiting frequent allelic losses but no allelic preference, one is localized
within a 2.9 cM region between D12Mit53 and D12Mit279 loci on chromosome 12, and
the other is near the D16Mit122/D16Mit162 loci on chromosome 16. The frequency of
allelic loss in the D12Mit279 region is 62% and does not differ in tumors between
the presence and absence of the p53-deficient allele. In contrast, the loss
frequency of D16Mit122 is raised by the existence of p53-deficient allele: 62%
for p63(-/+) and 13% for p53(+/+), suggesting co-operative function of the two
losses. The D12Mit279 and D16Mit122 regions probably harbor different types of
tumor suppressor gene that play key roles in lymphoma development.
PMID- 9652742
TI - Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and
chromosomal instability.
AB - We have examined defects in mammary development and tumorigenesis in a transgenic
model expressing the c-myc gene under the MMTV-LTR promoter. The stochastic
tumors which arise from hyperplastic ductal and lobular lesions in this model are
characterized by high rates both of apoptosis and of chromosomal instability.
Since the p53 gene product is thought to be central in the maintenance of genomic
integrity, in part due to its ability to induce apoptosis in cells harboring DNA
damage, we examined its expression and possible mutation. Initially, we observed
that unmutated p53 is strongly expressed in premalignant mammary glands and in
mammary tumors derived from the MMTV-c-myc strain. We then mated the MMTV-myc
strain to a p53-deficient strain as a means of examining the effect of this
lesion on mammary development and tumorigenesis in the context of c-myc
overexpression. A lack of both p53 alleles in the presence of c-myc
overexpression resulted in a dramatic hyerplastic alteration in mammary gland
development. Specifically, in female bitransgenic MMTV-c-myc/p53 null mice (MMTV
myc/p53(-/-)), lobular hyperplasias were observed at almost every ductal end bud
as early as 32 days of age. In contrast, only mild ductal and lobular
hyperplasias were seen in MMTV-myc mice that contained both p53 alleles (MMTV
myc/p53(+/+)); an intermediate phenotype occurred in mice with a single intact
(MMTV-myc/p53(+/-)) p53 allele. Mammary carcinomas arose with a high frequency in
MMTV-myc/p53(+/-) mice; the tumors were comparable in frequency, histology and
apoptotic index to the tumors in MMTV-myc/p53(+/+) mice. Also, as previously
observed (Elson et al., 1995), lymphomas arose with extremely short latency in
MMTV-myc/p53(-/-) mice, precluding study of the fate of their hyperplastic
mammary lesions in situ. The frequency of p53 mutations in MMTV-myc/p53(+/+) and
MMTV-myc/p53(+/-) mammary tumors and in cell lines derived from these tumors was
examined by direct sequencing. No point mutations or deletions in p53 were
observed in mammary tumors or cell lines from either genotype. Finally, a
detailed chromosomal analysis using multicolor spectral karyotyping (SKY)
revealed that there were multiple chromosomal alterations in the c-myc
overexpressing cells that contained either one or two unmutated p53 alleles.
Variable ploidy changes, a common translocation of chromosome 11, and other
chromosomal aberrations were observed. Our data thus support an interaction
between c-Myc and p53 in mammary development, but suggest that loss of p53 is
required neither for c-myc-dependent tumorigenesis nor for c-myc-dependent
chromosomal instability.
PMID- 9652743
TI - Mutations at coding mononucleotide repeats in gastric cancer with the
microsatellite mutator phenotype.
AB - We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding
repeats were associated with microsatellite instability (MSI). The tumors
included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI =
two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats
within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta
RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%),
four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in
MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No
alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6
were strongly associated to hMSH6 mutations, suggesting a key role of this gene.
The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed
in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI
positive GCs and were in most cases associated with mutations at coding repeats.
Further investigations with BAT-40 confirmed that four cases manifested
mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta
RII. A subset of tumors with MSI at two or more dinucleotide loci resulted
negative for mutations at coding and non-coding mononucleotide repeats.
PMID- 9652744
TI - Tec is involved in G protein-coupled receptor- and integrin-mediated signalings
in human blood platelets.
AB - Tec is a non-receptor type tyrosine kinase which is tyrosine phosphorylated and
activated upon stimulation of hematopoietic cells with various cytokines. The
role of Tec in G protein-coupled receptor- and integrin-mediated signalings has
not been elucidated. We therefore investigated the regulation of Tec in human
blood platelets. Tec was rapidly tyrosine phosphorylated in response to platelet
agonists which activate G protein-coupled receptors such as thromboxane A2 analog
(U46619), thrombin, and thrombin receptor activating peptide (TRAP). TRAP-induced
phosphorylation in Tec was significantly reduced under the conditions which
abrogate fibrinogen binding to GP IIb-IIIa and subsequent platelet aggregation.
However, TRAP induced significant levels of the phosphorylation even under these
conditions and also in thrombasthenic platelets which lack functional GP IIb-IIIa
molecules, suggesting that activation of G-protein-coupled receptor causes the
phosphorylation. To clarify whether integrin engagement by itself causes the
phosphorylation in Tec, we examined the state of the phosphorylation in platelets
activated by integrin engagement. Platelet adhesion to immobilized fibrinogen or
collagen induced significant levels of the phosphorylation. Furthermore, Tec was
translocated to cytoskeleton in response to TRAP in a manner dependent on
platelet aggregation, suggesting that Tec can be a component of integrin-mediated
signalings. These results collectively indicate that Tec is involved in G protein
coupled receptor- and integrin-mediated signalings in human blood platelets.
PMID- 9652745
TI - Isolation of a new protein factor required for activation of Raf-1 by Ha-Ras:
partial purification from rat brain cytosols.
AB - Ras-mediated signaling pathways play a critical role in cellular proliferation
and differentiation. Although it has been demonstrated that Ras interacts with
Raf-1 to stimulate the serine/threonine kinase activity of Raf-1, the precise
mechanism by which Ras activates Raf-1 remains obscure. To address this question,
we developed a cell-free system in which the activated form of H-Ras can induce
Raf-1 activation. Using this system, we found the presence of a new protein
factor, in cytosolic fractions of both human embryonic kidney 293 cells and rat
brain tissues, that is required for Ras-dependent activation of Raf-1. The factor
was purified from rat brain cytosols through successive column chromatographies
on DEAE Sephacel, SP Sepharose and Sephacryl S-300. The approximate molecular
weight of the activator was estimated as 400,000 by gel filtration. Its activity
was sensitive to heat and trypsin treatments. The purified activator did not
contain Src, 14-3-3, protein kinase C, JAK2 or Ksr-1, as judged by
immunoblotting. Further characterization of the activator is underway.
PMID- 9652746
TI - Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell
killing by low dose ionizing radiation in A431 human squamous carcinoma cells.
AB - The molecular mechanism(s) by which tumor cells survive after exposure to
ionizing radiation are not fully understood. Exposure of A431 cells to low doses
of radiation (1 Gy) caused prolonged activations of the mitogen activated protein
(MAP) kinase and stress activated protein (SAP) kinase pathways, and induced
p21(Cip-1/WAF1) via a MAP kinase dependent mechanism. In contrast, higher doses
of radiation (6 Gy) caused a much weaker activation of the MAP kinase cascade,
but a similar degree of SAP kinase cascade activation. In the presence of MAP
kinase blockade by the specific MEK1 inhibitor (PD98059) the basal activity of
the SAP kinase pathway was enhanced twofold, and the ability of a 1 Gy radiation
exposure to activate the SAP kinase pathway was increased approximately sixfold
60 min after irradiation. In the presence of MAP kinase blockade by PD98059 the
ability of a single 1 Gy exposure to cause double stranded DNA breaks (TUNEL
assay) was enhanced at least threefold over the following 24-48 h. The increase
in DNA damage within 48 h was also mirrored by a similar decrease in A431 cell
growth as judged by MTT assays over the next 4-8 days following radiation
exposure. This report demonstrates that the MAP kinase cascade is a key
cytoprotective pathway in A431 human squamous carcinoma cells which is activated
in response to clinically used doses of ionizing radiation. Inhibition of this
pathway potentiates the ability of low dose radiation exposure to induce cell
death in vitro.
PMID- 9652747
TI - Imprinted M6p/Igf2 receptor is mutated in rat liver tumors.
AB - We have previously shown that inactivation of mannose 6-phosphate/insulin-like
growth factor 2 receptor (M6P/IGF2R) is a common early event in both human liver
and breast carcinogenesis. The M6p/Igf2r is imprinted in mice while expression is
biallelic in most humans. In this investigation the M6p/Igf2r gene is shown to
also be imprinted in the liver of Fischer 344, Lewis and Brown Norway rats. In
addition, we have identified mutations in the expressed allele of the M6p/Igf2r
in 40% of diethylnitrosamine-initiated rat liver tumors. These results provide
further evidence that the M6P/IGF2R functions as a liver tumor suppressor gene.
They also suggest that mice and rats would be more sensitive than humans to those
hepatocarcinogens in which the M6p/Igf2r is mechanistically involved in
transformation since one rather than two alleles would need to be inactivated.
PMID- 9652748
TI - Inhibition of the MAP kinase cascade blocks heregulin-induced cell cycle
progression in T-47D human breast cancer cells.
AB - Members of the erbB family of receptor tyrosine kinases are commonly
overexpressed in human breast cancer. However, the relative contribution of
particular signalling pathways activated downstream of these receptors to the
mitogenic response of transformed breast epithelial cells remains poorly
characterized. Administration of heregulin-beta2 (HRG), a ligand for erbB3 and
erbB4, to growth arrested T-47D human breast cancer cells leads to activation of
both the PI3-kinase and MAP kinase signalling pathways and potent stimulation of
cell cycle progression. Specific inhibitors were used to assess the role of these
pathways in HRG-induced mitogenesis and to identify underlying mechanisms in
terms of regulation of gene expression. Treatment with the MEK inhibitor PD98059
led to a complete block of HRG-induced entry into S-phase, whilst administration
of the PI3-kinase inhibitor wortmannin resulted in only modest inhibition. In
addition, administration of PD98059 8 h after HRG was equipotent with
simultaneous administration in inhibiting entry into S-phase. However, delaying
addition for 14-16 h after HRG, when the cells were entering S-phase, was without
effect. HRG stimulation led to sequential induction of c-myc, cyclin D1, cyclin E
and cyclin A gene expression and hyperphosphorylation of the retinoblastoma
protein pRB. p21 (WAF1/CIP1/SDI1) gene expression was rapidly induced by HRG, but
significant changes in p27 (KIP1) protein levels were not detected. Preincubation
with PD98059 blocked the HRG-dependent induction of cyclin D1 mRNA, p21 and c-Myc
protein and pRB phosphorylation. These findings demonstrate that MEK activation
is critical to HRG-induced S-phase entry in these cells whilst PI3-kinase plays a
minor role. Moreover, these data are compatible with HRG-induced activation of
MEK being critical for a mid-G1 transition point and implicate c-myc and cyclin
D1 as key targets of the MAP kinase pathway involved in this response.
PMID- 9652749
TI - Absence of TSG101 transcript abnormalities in human cancers.
AB - The human TSG101 gene was cloned and mapped to chromosome 11p15, a site suspected
to contain a tumor suppressor gene involved in a variety of human cancers.
Subsequent investigation described the presence of abnormally spliced transcripts
and point mutations of TSG101 in breast cancer. Thus, we performed RT-PCR
amplification of the entire open reading frame of TSG101 to test for aberrant
transcripts in various human tumor cell lines derived from breast, bladder, head
and neck, and lung cancer. In addition, we performed RT-PCR on cDNA from primary
human breast and Wilms' tumor tissue. We found a single band of the expected size
in 10 of 11 breast cancers and 6 of 6 Wilms' tumor samples after the first round
of PCR. The remaining breast cancer sample displayed a barely visible smaller
band. However, aberrant bands appeared in most cases after performing nested PCR
casting doubt on the physiologic relevance of these spliced variants. We then
searched for small intragenic mutations by complete sequence analysis of TSG101
in breast cancer cell lines and tumors, as well as in Wilms' tumors and normal
fetal and adult kidney. No point mutations were found in any of the samples,
including four breast tumors with chromosomal loss at 11p15. We found no
consistent evidence of aberrant splicing or point mutations in breast cancer or
Wilms' tumor suggesting that TSG101 is not a primary target of inactivation in
human cancer.
PMID- 9652750
TI - Characterization of Wnt-1 and Wnt-2 induced growth alterations and signaling
pathways in NIH3T3 fibroblasts.
AB - Members of the Wnt family induce mouse mammary tumors and partially transform
mammary epithelial cells in culture. However, their mechanism of transformation
remains to be elucidated. In NIH3T3 mouse embryo fibroblasts, a standard
transformation model, Wnt-1 and Wnt-2 were shown to induce altered properties
including increased saturation density and growth in soft agar. Such cells also
exhibited increased cell-cell adhesiveness. However, unlike oncogenes such as
PDGFB or ras, Wnt-1 and -2 failed to induce detectable transformed foci following
transfection, and stable NIH3T3 transfectants lacked tumor forming capacity. Wnt
1 and -2 transfectants exhibited increased uncomplexed, cytosolic beta-catenin,
which was not observed with PDGFB, ras or erbB2 transfectants. In transient
transfection, Wnt-1 and -2 induced a rapid increase in cytosolic beta-catenin but
no detectable increase in the phosphorylated activated forms of MAP kinase. In
contrast, ras was a potent activator of MAP kinase but had no effect on free beta
catenin levels. These findings establish that both Wnt signaling and pattern of
growth alterations differ from those of oncogenes which activate proliferative
signaling pathways in NIH3T3 cells.
PMID- 9652751
TI - Inhibitory effects of malotilate on invasion and metastasis of rat mammary
carcinoma cells by modifying the functions of vascular endothelial cells.
AB - Malotilate (diisopropyl,1,3-dithiol-2-ylidenemalonate, MT) is clinically used as
a hepatoprotective agent. Because we noticed that MT induced the differentiation
of cultured vascular endothelial cells, we have examined its effects on lung
metastasis of the highly metastatic rat mammary carcinoma c-SST-2. MT was orally
administered to syngeneic SHR rats from 7 days before or after s.c. inoculation
of c-SST-2 cells to the end of the experiments. In the MT-treated rats, pulmonary
metastasis was markedly suppressed compared with the non-treated rats. In the
rats treated with MT for 19 days after i.v. inoculation of c-SST-2 cells, lung
metastasis was also significantly suppressed. An in vitro invasion assay using a
rat lung endothelial (RLE) cell monolayer revealed that pretreatment of the RLE
cells with MT, but not c-SST-2 cells, significantly reduced the invasion of the
RLE monolayer by c-SST-2 cells. An in vitro vascular permeability assay
demonstrated that MT prevented the increase in permeability of the RLE monolayer
by serum starvation. On the other hand, in vivo and in vitro growth, gelatinase
production and adhesion to the RLE cell monolayer of c-SST-2 cells were not
affected by MT treatment. These findings suggest that MT suppressed tumour
metastasis by intensifying the cell-to-cell contact of endothelial cells, thus
preventing tumour cells from invading vascular endothelium.
PMID- 9652752
TI - Induction of apoptosis by taxol and cisplatin and effect on cell cycle-related
proteins in cisplatin-sensitive and -resistant human ovarian cells.
AB - The effect of taxol (TX) and cisplatin (CDDP), singly or in association, was
assessed on two human ovarian cancer cell lines, one sensitive (A2780) and one
resistant (A2780 cp8) to CDDP. Cell lines showed a similar sensitivity to TX,
whereas different cytotoxicity results were obtained in the two cell lines as a
function of TX and CDDP sequence. Specifically, TX followed by CDDP induced
simply additive effects in both cell lines, whereas the opposite sequence
produced antagonistic effects in A2780 cells and synergistic effects in A2780 cp8
cells. TX, with or without CDDP, induced oligonucleosomal DNA fragmentation
typical of the apoptotic process, but the biochemical mechanisms undergoing
apoptosis were different in the two cell lines. In fact, in A2780 cells, TX (with
or without CDDP) treatment markedly increased p53 as well as p21waf1 protein
expression. In A2780 cp8 cells, drug treatment enhanced p53 levels, whereas the
expression of p21waf1 was always undetectable at mRNA and protein levels. In the
latter cell line, a premature activation of p34cdc2 kinase was observed in
correspondence with the drug-induced increase in the S-phase cell fraction. Such
an activation was not ascribable to an increase in the overall expression of
p34cdc2 or cyclin B1 proteins, but to a dephosphorylation of p34cdc2 kinase.
Overall, our results indicate that TX-induced apoptosis in human ovarian cancer
cells may be sustained by different events at the cell cycle-control level.
PMID- 9652753
TI - Reduction of tumour oxygenation during and after photodynamic therapy in vivo:
effects of fluence rate.
AB - It has been proposed that the generation of O2 during photodynamic therapy (PDT)
may lead to photochemical depletion of ambient tumour oxygen, thus causing acute
hypoxia and limiting treatment effectiveness. We have studied the effects of
fluence rate on pO2, in the murine RIF tumour during and after PDT using 5 mg kg(
1) Photofrin and fluence rates of 30, 75 or 150 mW cm(-2). Median pO2 before PDT
ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of
illumination, median tumour pO2 decreased with all fluence rates to values
between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if
illumination was interrupted. During prolonged illumination (20-50 J cm(-2)) pO2
recovered at the 30 mW cm(-2) fluence rate to a median value of 7.4 mmHg, but
remained low at the 150 mW cm(-2) fluence rate (median pO2 1.7 mmHg). Fluence
rate effects were not found after PDT, and at both 30 and 150 mW cm(-2) median
tumour pO2 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment
conclusion. PDT with 100 J cm(-2) at 30 mW cm(-2) caused significantly (P =
0.0004) longer median tumour regrowth times than PDT at 150 mW cm(-2), indicating
that lower fluence rate can improve PDT response. Vascular perfusion studies
uncovered significant fluence rate-dependent differences in the responses of the
normal and tumour vasculature. These data establish a direct relationship between
tumour pO2, the fluence rate applied during PDT and treatment outcome. The
findings are of immediate clinical relevance.
PMID- 9652754
TI - Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29
colon cancer cells.
AB - We hypothesized that unexplained increases in nucleoside triphosphates (NTP)
observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours
by DNA-damaging agents were related to chemotherapy-induced up-regulation of the
bcl-2 gene and DNA damage prevention and repair processes. To test this
hypothesis, we treated HT-29 cells with 10(-4) M nitrogen mustard (HN2) and
performed sequential perchloric acid extractions in replicate over 0-18 h. By
reference to an internal standard (methylene diphosphonic acid), absolute changes
in 31P-detectable high-energy phosphates in these extracts were determined and
correlated with changes in bcl-2 protein levels, cell viability, cell cycle,
apoptosis and total cellular glutathione (GSH) (an important defence against DNA
damage from alkylating agents). After HN2 administration, bcl-2 protein levels in
the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but
apoptosis measured using fluorescence techniques remained in the 1-4% range.
Increased cell division was noted at 4 h. Two high-energy interconvertible
phosphates, NTP (P < or = 0.006) and phosphocreatine (PCr) (P < or = 0.0002),
increased at 2 h concurrently with increased levels of bcl-2 protein and
glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated
by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased
NTP after chemotherapy.
PMID- 9652755
TI - Prolonged in vivo tumour retention of a human diabody targeting the extracellular
domain of human HER2/neu.
AB - Single-chain Fv (scFv) molecules exhibit highly specific tumour-targeting
properties in tumour-bearing mice. However, because of their smaller size and
monovalent binding, the quantities of radiolabelled scFv retained in tumours
limit their therapeutic applications. Diabodies are dimeric antibody-based
molecules composed of two non-covalently associated scFv that bind to antigen in
a divalent manner. In vitro, diabodies produced from the anti-HER2/neu (c-erbB-2)
scFv C6.5 displayed approximately 40-fold greater affinity for HER2/neu by
surface plasmon resonance biosensor measurements and significantly prolonged
association with antigen on the surface of SK-OV-3 cells (t1/2 cell surface
retention of > 5 h vs 5 min) compared with C6.5 scFv. In SK-OV-3 tumour-bearing
scid mice, radioiodinated C6.5 diabody displayed a highly favourable balance of
quantitative tumour retention and specificity. By as early as 4 h after i.v.
administration, significantly more diabody was retained in tumour (10 %ID g(-1))
than in blood (6.7 %ID ml(-1)) or normal tissue (liver, 2.8 %ID g(-1); lung, 7.1
%ID g(-1); kidney, 5.2 %ID g(-1)). Over the next 20 h, the quantity present in
blood and most tissues dropped approximately tenfold, while the tumour retained
6.5 %ID g(-1) or about two-thirds of its 4-h value. In contrast, the 24-h tumour
retention of radioiodinated C6.5 scFv monomer was only 1 %ID g(-1). When diabody
retentions were examined over the course of a 72-h study and cumulative area
under the curve (AUC) values were determined, the resulting tumor-organ AUC
ratios were found to be superior to those previously reported for other
monovalent or divalent scFv molecules. In conclusion, the diabody format provides
the C6.5 molecule with a distinct in vitro and in vivo targeting advantage and
has promise as a delivery vehicle for therapeutic agents.
PMID- 9652756
TI - Immune stimulatory potential of B7.1 and B7.2 retrovirally transduced melanoma
cells: suppression by interleukin 10.
AB - The immunostimulatory capacities of B7.1-and B7.2- expressing melanoma cells were
investigated. A365, 960306 and 950504 melanomas, established from nodular
melanoma lesions, were retrovirally transduced. Irradiated B7-, B7.1+ and B7.2+
melanoma cells were co-cultured with autologous or allogeneic peripheral blood
mononuclear cells (PBMCs). Proliferation was assessed by [3H]thymidine uptake.
mRNA encoding for interleukin 2 (IL-2), IL-4, IL-10 and interferon gamma (IFN
gamma) was determined. IFN-gamma, IL-2, IL-4 and IL-10 secretion were quantitated
by ELISA. B7.1+ and B7.2+ melanomas induced proliferation of PBMCs and mRNA for
IL-2 and IFN-gamma. After co-incubation of transduced melanoma cells with PBMCs,
high levels of IL-10 were detectable in the supernatant. The presence of
neutralizing anti-IL-10 antibodies resulted in enhanced proliferation and IL-2
and IFN-gamma secretion. Our data indicate that B7.1- and B7.2-transduced
melanoma cells trigger lymphocytic proliferation with transcription of IL-10, IL
2 and IFN-gamma. Blocking of IL-10 augments these effects. Gene therapy protocols
using tumour cells as a vaccine have to consider the adverse effects of IL-10.
PMID- 9652757
TI - Hepatocyte growth factor-stimulated renal tubular mitogenesis: effects on
expression of c-myc, c-fos, c-met, VEGF and the VHL tumour-suppressor and related
genes.
AB - Hepatocyte growth factor (HGF/SF) is a potent renal proximal tubular cell (PTEC)
mitogen involved in renal development. HGF/SF is the functional ligand for the c
met proto-oncogene, and germline c-met mutations are associated with familial
papillary renal cell carcinoma. Somatic von Hippel-Lindau disease tumour
suppressor gene (VHL) mutations are frequently detected in sporadic clear cell
renal cell carcinomas (RCC), and germline VHL mutations are the commonest cause
of familial clear cell RCC. pVHL binds to the positive regulatory components of
the trimeric elongin (SIII) complex (elongins B and C) and has been observed to
deregulate expression of the vascular endothelial growth factor (VEGF) gene.
HGF/SF has similarly been reported to up-regulate expression of the VEGF gene in
non-renal experimental systems. To investigate the mechanism of HGF/SF action in
PTECs and, specifically, to examine potential interactions between the HGF/c-met
and the VHL-mediated pathways for renal tubular growth control, we have isolated
untransformed PTECs from normal kidneys, developed conditions for their culture
in vitro and used these cells to investigate changes in mRNA levels of the VHL,
elongin A, B and C, VEGF, c-myc, c-fos and c-met genes after HGF/SF exposure.
Significant elevations in the mRNA levels of VEGF, c-myc, c-fos, c-met and
elongins A, B and C, but not VHL, were detected after HGF/SF stimulation of human
PTECs (P < 0.02), with a consistent order of peak levels observed over successive
replicates (c-fos at 1 h, VEGF at 2-4 h, c-myc, at 4 h, followed by c-met and all
three elongin subunits at 8 h). This study highlights the spectrum of changes in
gene expression observed in PTECs after HGF/SF stimulation and has identified
possible candidate mediators of the HGF/SF-induced mitogenic response. Our
evidence would suggest that the changes in PTEC VEGF expression induced by HGF/SF
are mediated by a VHL-independent pathway.
PMID- 9652758
TI - Wt-p53 action in human leukaemia cell lines corresponding to different stages of
differentiation.
AB - Recent studies support the potential application of the wt-p53 gene in cancer
therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia
phenotypes by acting on cell survival, proliferation and/or differentiation. As
for tumour gene therapy, the final fate of the neoplastic cells is one of the
most relevant points. We examined the effects of exogenous wt-p53 gene expression
in several leukaemia cell lines to identify p53-responsive leukaemia. The
temperature-sensitive p53Val135 mutant or the human wt-p53 cDNA was transduced in
leukaemia cell lines representative of different acute leukaemia FAB subtypes,
including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well
as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing
diverse differentiation features. By morphological, molecular and biochemical
analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis
only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC
CML showing morphological and cytochemical features of undifferentiated blast
cells. In contrast, it promotes differentiation in the others. Interestingly,
cell responsiveness was independent of the vector used and the status of the
endogenous p53 gene.
PMID- 9652759
TI - Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive
carcinoma of the breast.
AB - Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an
associated invasive component, were studied for loss of heterozygosity (LOH) of
microsatellite markers on chromosome 9p and the results compared with a panel of
20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome
9p is also thought to contain other putative tumour-suppressor genes. If the
three panels of breast tumours showed LOH of markers in this region this would
suggest that such putative genes were important in breast carcinogenesis. By
studying both preinvasive and invasive breast tumours, it should also be possible
to gain further information about the relationship between lesions of a different
stage and to determine whether DCIS is indeed a precursor of invasive ductal
carcinoma. Levels of LOH were low in the invasive-only set of tumours.
Surprisingly, considerably higher levels of loss were observed in the tumours
with an in situ component. Also, much heterogeneity was observed between
different DCIS ducts or invasive tumour and DCIS from the same case.
PMID- 9652760
TI - SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2
expression.
AB - New therapeutic strategies are now being developed against adenocarcinoma
associated with erbB-2 amplification, particularly by inhibiting p185erbB-2
expression. Antisense oligodeoxynucleotides seem promising for this purpose as
long as they are efficiently protected against degradation and targeted into the
cells. We present antisense oligonucleotide carriers, the supramolecular
biovectors (SMBVs), for which we have already demonstrated the ability to improve
both cellular uptake and protection of oligodeoxynucleotide. The present work
demonstrates that SMBVs elicit a specific and non-toxic action of antisense
compounds in a cell model, irrespective of their sensitivity to nucleases. This
is a major point, considering the specificity problems associated with the use of
nuclease-resistant phosphorothioate oligodeoxynucleotide. SMBVs improve antisense
efficiency of oligodeoxynucleotide designed against p185erbB-2, with a complete
growth arrest of SK-Br-3, human adenocarcinoma mammary cells that overexpress
p185erbB-2 and no effect on MCF-7 cells that normally express p185erbB-2. The
comparison of SMBVs with DOTAP reveals the statistically higher efficiency of
SMBVs, which allows the antisense inhibition of p185erbB-2 expression in 65-75%
of SK-Br-3 cells (P < 0.05). The efficiency and controlled synthesis of SMBVs
underline their potentialities as oligodeoxynucleotide carriers for in vivo
experiments.
PMID- 9652761
TI - Down-regulation of Fas gene expression in colon cancer is not a result of allelic
loss or gene rearrangement.
AB - Expression of Fas, an apoptosis-inducing receptor, in colonic epithelium is
progressively reduced during malignant transformation. We have examined the human
Fas gene for loss of heterozygosity (LOH) and gross rearrangements in colon
tumours and matched normal mucosa. Polymerase chain reaction (PCR) primers were
designed to span a DraI restriction fragment length polymorphic site in the gene.
Heterozygosity was detected in normal DNA samples by PCR amplification of the
polymorphic site and restriction enzyme digestion. Thirty-eight of 88 patients
(43%) with colon carcinomas were informative for the assay, and LOH was detected
in 6 of the 38 (16%) corresponding tumours. Tumours from three patients with LOH
did not express detectable Fas mRNA, and Fas expression was reduced or absent in
7 of 11 tumours from informative patients without LOH. Southern blotting of
tumour DNA samples was used to detect rearrangement of the Fas gene, but no
altered hybridization patterns were observed in 64 tumours analysed. These
findings indicate that disruption of the Fas gene is not primarily responsible
for the loss of Fas protein expression reported in colon cancer. We have also
shown that loss of Fas gene transcription is common in these tumours, which may
be due to epigenetic gene silencing.
PMID- 9652762
TI - Frequent alterations of cell cycle regulators in early-stage breast lesions as
detected by immunohistochemistry.
AB - Progression through G1 phase of the eukaryotic cell cycle is tightly controlled
by cyclin-dependent kinases (CDK). These proteins form part of a regulatory
pathway including the cyclin-dependent kinase inhibitor (CKI) p16, D-type cyclins
and the product of the retinoblastoma gene pRb. Aberration of any one of these
components may lead to uncontrolled proliferation contributing to neoplasia.
Three of these proteins, cyclin D1, pRb and p16, were analysed by
immunohistochemistry on archival paraffin sections to determine whether
expression patterns were different in preinvasive ductal carcinoma in situ (DCIS)
and invasive breast tumours relative to normal. Genetic analysis of the gene
encoding cyclin D1 (CCND1) was also carried out, using an intragenic restriction
fragment-length polymorphism (RFLP) to assess possible allelic imbalance. A
majority of the tumours studied (approximately 90%) showed abnormalities in
expression of at least one of these proteins. Overexpression of cyclin D1 was
found in approximately 49% cases, reduced expression of p16 in approximately 46%
and reduced expression of pRb in approximately 37%. Allelic imbalance of cyclin
D1 was found in approximately 57% cases.
PMID- 9652763
TI - Immunohistochemical detection of DNA topoisomerase IIalpha, P-glycoprotein and
multidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer.
AB - Non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) differ
significantly in their clinical response to topoisomerase IIalpha (topo-IIalpha)
directed drugs, such as etoposide and teniposide, as NSCLC is virtually
insensitive to single-agent therapy, while SCLC responds in two-thirds of cases.
Preclinical studies have indicated that resistance to topo-IIalpha drugs depends
on topo-IIalpha content and/or activity, the altered-topo-II multidrug resistance
phenotype (at-MDR) and/or one of two different drug efflux pumps, P-glycoprotein
(P-gp) and the multidrug resistance protein (MRP). Immunohistochemical analysis
on paraffin-embedded tissue from 27 cases of untreated NSCLC and 29 cases of
untreated SCLC (of which additional tumour biopsies after treatment with topo
IIalpha-directed drugs were available in ten cases) yielded the following
results: NSCLC had significantly less topo-IIalpha than SCLC (P < 0.0001), as
only 5 out of 27 NSCLC cases had > 5% positive cells compared with 28 out of 29
SCLC, and 0 out of 27 NSCLC had > 25% positive cells compared with 26 out of 29
SCLC. P-gp was detected in > 5% of cells in only 3 out of 27 NSCLC and in 6 out
of 29 SCLC, and MRP in 5 out of 27 of NSCLC and 9 out of 29 SCLC. After treatment
of patients with SCLC with either etoposide or teniposide, which are topo-IIalpha
directed drugs, there was an increase in MRP (P < 0.1) and P-gp (P < 0.05)
positivity, while topo-IIalpha decreased (P < 0.05). In conclusion, the major
difference between untreated NSCLC and SCLC was in topo-IIalpha content. In the
small series of ten patients treated for SCLC, all three MDR phenotypes appeared
to increase.
PMID- 9652764
TI - Randomized trial comparing protracted infusion of 5-fluorouracil with weekly
doxorubicin and cyclophosphamide with a monthly bolus FAC regimen in metastatic
breast carcinoma (SPM90).
AB - Infusional 5-fluorouracil in advanced breast cancer has been associated with
improved clinical response rates when compared with conventional bolus therapy.
As a first line of chemotherapy in proven metastatic breast carcinoma, 258 women
were randomly assigned to receive FAC consisting of 5-fluorouracil (F) 600 mg m(
2) intravenously (i.v.) over 1 h on days 1, 2 and 3, doxorubicin (A) 50 mg m(-2)
i.v. bolus on day 1 and cyclophosphamide (C), 400 mg m(-2) i.v. bolus on days 1,
2 and 3 or 'FULON' consisting of 5-fluorouracil 250 mg m(-2) day(-1) continuously
infused from day 1 to day 22, doxorubicin 15 mg m(-2) i.v. bolus on days 1, 8, 15
and 22 and cyclophosphamide 300 mg m(-2) i.v. bolus on days 1, 8, 15 and 22.
Chemotherapy courses were administered 4-weekly for the bolus regimen and 6
weekly for FULON. Pretreatment characteristics were identical between the two
groups. Response rates were 54% in the FAC arm and 53% in the FULON arm. Time to
progression was 14 months in the FAC arm and 12 months in the FULON arm.
Differences were not statistically significant. Median overall survival duration
for all patients was 22 months. Haematological toxicity was more severe in the
bolus-treated group (P = 0.05), as were nausea and vomiting (P < or = 0.01). We
conclude that the two regimens appeared equally effective but have different
toxicities.
PMID- 9652765
TI - Bolus/infusional 5-fluorouracil and folinic acid. A report on two prospective,
consecutive phase II studies with 5-fluorouracil dose escalation.
AB - We have used a relatively new trial methodology, the group sequential design, to
prospectively evaluate two dose levels of bolus/infusional 5-fluorouracil (5-FU)
and folinic acid in 192 consecutive-patients with advanced colorectal carcinoma.
On day 1, all patients received 200 mg m(-2) of folinic acid infusion over 2 h.
Cohort A (n = 102 patients) received 500 mg m(-2) 5-FU by i.v. 15-min infusion
followed by an infusion of 500 mg m(-2) 5-FU over 22 h. Treatment was repeated on
day 2 and further cycles given 2-weekly. After sequential analysis excluded a
response rate of over 40%, cohort B (n = 90 patients) received an increased dose
of 600 mg m(-2) 5-FU bolus and infusion. Patients had received no prior 5-FU
therapy and the two cohorts had similar demographic features. In 179 evaluable
patients, the overall response rate was 18% (95% CI 12-24%) with CR of 6% and PR
of 12%, with no difference between the two cohorts. Overall median survival was
34 weeks (95% CI 30-39) with no significant difference between cohorts (median
survival 32 and 37 weeks in cohort A and B respectively; P = 0.27). On
multivariate analysis, poor performance status, elevated initial WBC and alkaline
phosphatase and low serum albumin were associated with reduced survival (P <
0.05), and initial raised WBC showed an association with reduced likelihood of
response (P = 0.002). Overall toxicity was low with CTC grade 3 mucositis,
diarrhoea, nausea or vomiting in < or = 6% of patients and no treatment-related
deaths. Significant (grade 3 or above) leucopenia was more common in cohort B
than in cohort A (9% and 1% respectively); there were more dose reductions, and
the median administered dose intensity was lower in cohort B than in cohort A
(89% and 97% respectively; P = 0.006). In this group of relatively unselected
patients, we have confirmed a relatively low objective response rate and median
survival of 7.8 months with this regimen. There was no significant difference in
outcome between the two dose levels but the higher dose of 5-FU was associated
with more dose reductions and greater toxicity.
PMID- 9652766
TI - Initial high anti-emetic efficacy of granisetron with dexamethasone is not
maintained over repeated cycles.
AB - We have reported previously that the anti-emetic efficacy of single agent 5HT3
antagonists is not maintained when analysed with the measurement of cumulative
probabilities. Presently, the most effective anti-emetic regimen is a combination
of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment
of efficacy of such a combination in 125 patients, scheduled to receive cisplatin
> or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs.
Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of
granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg
of dexamethasone and 1 mg of granisetron twice daily by oral administration.
Protection was assessed during all cycles and calculated based on cumulative
probability analyses using the method of Kaplan-Meier and a model for
transitional probabilities. Irrespective of the type of analysis used, the anti
emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial
complete acute emesis protection rate of 66% decreased to 30% according to the
method of Kaplan-Meier and to 39% using the model for transitional probabilities.
For delayed emesis, the initial complete protection rate of 52% decreased to 21%
(Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed
that protection failure in the delayed emesis period adversely influenced the
acute emesis protection in the next cycle. We conclude that the anti-emetic
efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple
cycles of highly emetogenic chemotherapy, and that the acute emesis protection is
adversely influenced by protection failure in the delayed emesis phase.
PMID- 9652767
TI - Elevated plasma levels of transforming growth factor (TGF)-beta1 and TGF-beta2 in
patients with disseminated malignant melanoma.
AB - Overexpression of transforming growth factor-beta isoforms (TGF-beta1, -beta2,
beta3) has been previously reported in human melanoma cell lines and tumours. The
aim of the present study was to evaluate the plasma levels of TGF-beta isoforms
in melanoma patients. Significantly elevated levels of TGF-beta1 (4.2 x the
controls, P = 0.0094) and of TGF-beta2 (1.5 x the controls, P = 0.012) but not of
TGF-beta3 were measured in patients with disseminated but not locoregional
melanoma. These results indicate systemic circulation of potentially
immunosuppressive peptides of the TGF-beta family in end-stage melanoma patients.
PMID- 9652768
TI - Prognostic value of urokinase plasminogen activator in primary breast carcinoma:
comparison of two immunoassay methods.
AB - Urokinase-type plasminogen activator (uPA) is a potentially important prognostic
factor in breast cancer for identifying patients at high risk of recurrence. This
retrospective study assessed two enzyme-linked immunosorbent assay (ELISA)
methods measuring uPA antigen levels in 499 primary breast cancer cytosols. Both
uPA methods were applied to cytosols used routinely for oestrogen (ER) and
progesterone (PgR) receptor assays. uPA was determined using a classical ELISA
method (Imubind; American Diagnostica) and a novel automatic immunoluminometric
assay (Lia; Sangtec Medical). The uPA Imubind method revealed about twice as much
uPA antigen (median 0.75 ng mg(-1) protein) as the uPA Lia method (median 0.38 ng
mg(-1) protein). The correlation coefficient between the two methods was
acceptable (r = 0.81), but the two techniques are not interchangeable. Univariate
analyses confirmed the poor outcome of patients whose tumours contained large
amounts of uPA, regardless of the technique used. Multivariate analyses showed
that uPA Imubind and uPA Lia values were both strong independent prognostic
factors.
PMID- 9652769
TI - Cell proliferation measured by MIB1 and timing of surgery for breast cancer.
AB - We have investigated the use of the antibody MIB1 as a proliferative and
prognostic marker in breast cancer and whether changes in proliferative activity
could account for differences in prognosis of premenopausal women operated on
during different phases of the menstrual cycle. MIB1 expression was strongly
correlated with S-phase fraction and histological grade. There was no difference
in MIB1 scores between different phases of the menstrual cycle. Both MIB1 score
and timing of surgery correlated significantly with duration of survival, while
the two together were even stronger predictors of overall survival. Women with
slowly proliferating tumours surgically removed in the luteal phase had a very
good prognosis, whereas women with rapidly proliferating tumours excised at other
times of the cycle had a worse prognosis.
PMID- 9652770
TI - Hypertension, obesity and their medications in relation to renal cell carcinoma.
AB - A population-based, case-control study was conducted in Los Angeles County,
California, to investigate the inter-relationships of obesity, hypertension and
medications in relation to renal cell carcinoma (RCC) risk. A total of 1204 RCC
patients and an equal number of neighbourhood controls were included. Obesity was
a strong risk factor for RCC. A fourfold increase in risk was observed for those
with usual body mass index (kg m(-2)) of > or = 30 vs < 22. A history of
hypertension was another strong, independent risk factor for RCC [odds ratio (OR)
= 2.2; 95% confidence interval (CI) = 1.8, 2.6]. There was little evidence that
use of diuretics was directly related to RCC development. Use of diuretics for
reasons other than hypertension (primarily for weight control) was unrelated to
risk among self-reported normotensive subjects (OR = 1.2; 95% CI = 0.7, 2.2).
Among hypertensive subjects, heavy users of diuretics experienced similar risk as
light users (OR = 0.9 among subjects with lifetime dose of > or = 137 g compared
with those with lifetime dose of < 43 g). Similarly, normotensive subjects who
took non-diuretic antihypertensives regularly showed no increased risk for RCC
(OR = 1.1; 95% CI = 0.6-1.8), and intake among hypertensive subjects did not
further increase their risk. Regular use of amphetamine-containing diet pills was
associated with a twofold increase in RCC risk (95% CI = 1.4-2.8) and the risk
increased with increasing dose of amphetamines. However, the fraction of cases
possibly related to this exposure is small (population-attributable risk = 5%).
PMID- 9652771
TI - Survival analysis of 5595 head and neck cancers--results of conventional
treatment in a high-risk population.
AB - This is a study of 5595 head and neck cancer patients treated during 1987-89 at
TMH, Mumbai. The study included 1970 oral cancers (ICD 140-145), 1495
oropharyngeal cancers (ICD 1410, 1453, 146), 1255 hypopharyngeal cancers (ICD
148), 125 nasopharyngeal cancers (ICD 147) and 750 laryngeal cancers (ICD 161).
The clinical extent of disease at presentation was based on TNM group staging
(UICC 1978). For the majority of sites, patients attended the hospital during
stage III and stage IV of the disease; the only exception was for cancers of the
lower lip, anterior tongue and vocal cord when between 46.2% and 56.5% of
patients with localized cancer (stage I and II) were seen. Generally, surgery
either alone or with radiation has been administered for oral cancer patients
whereas radiation either alone or in combination with chemotherapy was
administered for other head and neck sites. The overall 5-year survival rate was
in the range of 20-43% for oral cancer, 8-25% for pharyngeal cancers and 25-62%
for laryngeal cancer. The 5-year relative survival rates were more or less in
agreement with the results published by the Eurocare study for head and neck
cancers. The importance of primary prevention in head and neck cancer is
stressed.
PMID- 9652772
TI - Breast cancer in Norway 1970-1993: a population-based study on incidence,
mortality and survival.
AB - The incidence, mortality and survival of breast cancer patients from 1970 to 1993
were studied using data from the Cancer Registry of Norway. The age-adjusted
incidence rate increased from 62.0 to 76.9 per 100,000 person-years during the
period, and more than 2000 cases are now registered annually. The increase tends
to be highest in the age group below 40 years. The increase is mainly found in
cases with localized tumours at the time of diagnosis. The mortality rate has
been almost unchanged in the period; the age adjusted mortality rate is 27.0 per
100,000 person-years at the end of the study period. The 5-year overall survival
has increased among cases with axillary lymph node metastases at the time of
diagnosis; the other stages show only little improvement.
PMID- 9652773
TI - The effects of interaction between familial and reproductive factors on breast
cancer risk: a combined analysis of seven case-control studies.
AB - In this paper, a combined analysis was performed to study the interaction between
familial risk and reproductive life factors. In particular, the interaction
between familial risk and breast cell mitotic activity (BCMA), as assessed by
duration of ovarian activity, was investigated because of the potential
importance of mitotic activity on genetically susceptible cells. The present
analysis included 3152 cases and 4404 controls in seven case-control studies from
four countries. The interaction effect was estimated in each study separately,
then combined using two different methods: a multivariate weighted average and a
Bayesian random-effects model. The main effects of reproductive life factors on
the risk of breast cancer were in agreement with the previous findings. In
particular, an increased duration of BCMA before the first childbirth and over
life was found to increase the risk of breast cancer (P < 0.001). Slightly
increasing but non-significant, familial risks were observed with increasing
number of children (P = 0.17), increasing age at first childbirth (P > 0.2) and
increasing duration of BCMA (P > 0.2). There was no modification in familial risk
with age at menarche and no clear pattern with menopause characteristics. A weak
influence of reproductive and menstrual factors on the familial risk emerged from
the present study.
PMID- 9652775
TI - From Mendel to the millennium: the genome project.
PMID- 9652774
TI - Segregation analysis of epithelial ovarian cancer in Finland.
AB - Epithelial ovarian cancer is known to aggregate in families. The dominantly
inherited ovarian cancer predisposing genes, BRCA1, BRCA2 and genes involved in
the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently
been identified. However, in the majority of families with more than one case of
ovarian cancer, dominant inheritance cannot be recognized. We investigated
familial clustering of epithelial ovarian cancer in a population-based sample of
663 Finnish ovarian cancer patients. A segregation analysis with the POINTER
software was conducted on the 937 nuclear families from these 663 pedigrees. The
major gene model was favoured, and the sporadic and multifactorial models were
strongly rejected. In the studied population, the best fitting model was a
recessive mode of inheritance, and 8% of ovarian cancer patients were estimated
to be homozygous for the deleterious genotype. This evidence for recessively
inherited ovarian cancer predisposition should be interpreted cautiously, as the
analysis is subject to certain errors, which are discussed in the article.
Results of this analysis, however, strongly emphasize the role of genetic factors
in all familial aggregation of epithelial ovarian cancer.
PMID- 9652776
TI - Do neurological disorders in childhood pose a risk for mental health in young
adulthood?
AB - To assess whether juvenile-onset epilepsy or motor disability is complicated by
an increased number of mental health disorders or experience of psychosomatic
symptoms in young adulthood, we studied 81 subjects with epilepsy and 52 with
motor disabilities at the age of 19 to 25 years and compared them with 211
controls. The main diagnostic tool, the Present State Examination, was
administered to those attending the interviews in person who were of normal
intelligence; there were 62, 38, and 123 subjects in the three categories,
respectively. Compared with the controls, the subjects with epilepsy showed an
equal prevalence of psychiatric disorders whereas those with motor disabilities
had a significantly higher prevalence, particularly of depressive disorders. The
reported prevalence of psychosomatic symptoms confirmed this main result.
Psychological illness affected everyday life of two out of five subjects with
motor disabilities, but only half of those in the other two groups. It is
concluded that motor disability since childhood, but not epilepsy, could be a
factor that increases susceptibility to psychiatric morbidity, especially
depression, and causes a large number of psychosomatic symptoms. The results
challenge staff of clinics working with such adolescents to find individual
approaches in preventing the negative influence of psychological disorders on
social life.
PMID- 9652777
TI - Life expectancy of adults with cerebral palsy.
AB - To determine the predictors of mortality and find the life expectancies of adults
with cerebral palsy (CP), data on 24,768 individuals aged 15 years and over who
received services in California between January 1980 and December 1995 were
analyzed. Multivariate statistical methods to identify mortality predictors, and
actuarial methods to determine corresponding life expectancies were used. The key
predictors were lack of basic functional skills: mobility and feeding. Adults
lacking these skills had much reduced life expectancies, as short as 11 years for
the worst functioning groups. By contrast, survival of high-functioning adults
was close to that of the general population. The influence on survival of
cognitive skills, type of CP, and other factors appears to be expressed largely
through their effect on basic functioning. Life expectancies of adults of a given
age can differ by 40 years or more, according to their functional level.
PMID- 9652778
TI - Survival in cerebral palsy: the role of severity and diagnostic labels.
AB - The aim of this study was to review survival and certified causes of death of 584
children on a population-based register of cerebral palsy (CP), and to assess the
impact on these of an additional diagnostic label. The register, established in
1985, comprised children with CP born from 1980 to about 1987 who were resident
at the time of notification in the south-east of England in a region with between
3 and 4 million population, defined by the boundaries of the regional health
authority (North East Thames Regional Health Authority). The current report
concerns deaths of residents born between 1980 and 1986, who had been registered
but had later died, as well as of eligible children who had not been registered
while alive but whose cause of death was CP. These were identified at the Office
of Population Censuses and Surveys who also supplied copies of death certificates
for this study. For children notified while alive, information about motor
severity and other diagnostic labels was sought at entry to the register and
again between 3.5 and 4 years and between 7 and 8 years. For this study, children
known to have a postneonatal onset, a progressive or non-cerebral cause of motor
signs, or minimal motor involvement were excluded. Thirty-nine of 584 children
included in this study had died by the end of 1995. No deaths had occurred in
children known to have less than four-limb involvement. Survival of the group
known to have an additional diagnostic label was significantly lower (86.2%) than
that of the group with no known label (96.3%; P=0.01), and remained lower,
although not significantly, if only those with severe four-limb involvement were
compared (75.3% versus 92.4%; P=0.2). The greater severity of limb involvement in
those with an additional diagnosis may not account for this difference. Of the 37
children with death certificates available, CP was mentioned as a cause in only
24.
PMID- 9652779
TI - Speech and language development of children born at < or = 32 weeks' gestation: a
5-year prospective follow-up study.
AB - Speech and language comprehension and production were assessed at the age of 5
years in a cohort of children born preterm at < or = 32 weeks' gestational age
(N=55) in comparison with children born at term and of similar age, sex, and
social backgrounds. Data both including and excluding major neurological
disabilities are presented. Mean performance for the entire group of preterm
children was significantly lower than for the controls on most of the measures
including the composite IQ scores. When the nine children who had major
neurological disabilities were excluded from the preterm group, statistically
significant differences were found on four of the total 12 speech and language
measures. Intellectually normal preterm children without major neurological
disability were slower than the controls on rapid word retrieval. In addition,
difficulties in comprehending relative concepts were typical for the preterm
children. The results suggest 'subtle dysnomia', which is indicative of later
reading problems. On global verbal measures and on the basic speech and language
aspects the study groups did not differ. Specific language impairment, defined as
a discrepancy of > 1SD between Performance IQ and Verbal IQ scores, showed a
tendency to be more common in the control group. Within both the study groups,
the boys showed a tendency for a greater discrepancy between their Performance
and Verbal IQ scores.
PMID- 9652780
TI - A dyspraxic deficit in specific language impairment and developmental
coordination disorder? Evidence from hand and arm movements.
AB - The extent to which children with either specific language impairment (SLI) or
developmental coordination disorder (DCD) could be considered dyspraxic was
examined using three tasks involving either familiar, or unfamiliar actions. SLI
is diagnosed in children who fail to develop language in the normal fashion for
no apparent reason, while the DCD diagnosis is applied to a child who experiences
problems with movement in the absence of other difficulties. Seventy-two children
aged between 5 and 13 years participated, falling into one of four groups: (1)
children with specific language impairment (SLI), (2) children with developmental
coordination disorder (DCD), (3) age-matched control children, and (4) younger
control children. The performance of the clinical groups resembled that of
younger normally developing children. Children with SLI, DCD, and the younger
controls showed significant difficulty on the task requiring the production of
familiar, but not unfamiliar postures. The deficit observed in the SLI group is
particularly striking because it was seen both in those with and those without
recognized motor difficulties.
PMID- 9652781
TI - Interlimb coupling in children with hemiplegic cerebral palsy during reaching and
grasping at speed.
AB - This investigation examined reaching and grasping at speed in children with
hemiplegic cerebral palsy. Of particular interest was the effect of the movement
of the less affected limb on the more affected one. Using 3D kinematic analysis
and standard video recordings, 11 children with hemiplegia of varying degrees of
severity were examined performing three reaching tasks at speed. The data were
analysed and the extent and nature of the interlimb coupling occurring in each
child were assessed using a number of different variables. The results are
discussed in terms of spatial, temporal, and postural coupling. All children
coupled to some degree but differed in the degree and type of coupling. Speed
facilitated coupling which was stronger during the first part of the movement in
all three tasks. The variables affecting coupling included the type of coupling,
the nature of the task, the importance of context, and the stage in the movement.
PMID- 9652782
TI - The predictive value of developmental testing of extremely jaundiced African
infants.
AB - The predictive value of the Neonatal Neurological Examination (NNE) adapted from
Prechtl (1977) and the Infant Motor Screen (IMS) from Nickel (1989) at 4 months
was studied in severely jaundiced infants in Zimbabwe. Fifty infants were
examined with the NNE, 41 with the IMS and 43 with the Bayley Scales of Infant
Development (BSID) (Bayley 1969). Five infants had choreoathetosis and six had a
motor delay at age 1 year. The NNE and IMS proved to be sensitive instruments
particularly when two infants who became malnourished after the neonatal period
were excluded. Logistic regression was used to investigate the relation between
the BSID and five selected predictors from the NNE. This resulted in a correct
classification of 93%. By using only the predictors acoustic blink and traction
response, 80% of the infants were correctly classified but the number of false
negatives was reduced from three to one.
PMID- 9652783
TI - Turkish children's performance on Denver II: effect of sex and mother's
education.
AB - One thousand and ninety-one healthy Turkish children were tested with the Denver
II developmental screening test and the data were analysed for sex and
sociocultural differences. Few and inconsistent differences were observed between
boys and girls. On the other hand, there were marked differences between
sociocultural groups, particularly in terms of fine motor and language areas and
in older preschool children. The effect of maternal education on the child's
development is more important in countries where preschool education is not
commonly available. Whether this effect diminishes after 1 or 2 years of
schooling is to be investigated.
PMID- 9652784
TI - Evolution of a form of pure alexia without agraphia in a child sustaining
occipital lobe infarction at 2 1/2 years.
AB - The progress of cognitive visual dysfunction over an 8-year period of a child who
sustained bilateral occipital-lobe infarctions at the age of 2 1/2 years is
described. She survived with normal intelligence and went on to attend mainstream
school. She manifested many features of cognitive visual impairment and, in
particular, developed a form of pure alexia without agraphia. She achieved some
letter-by-letter reading but no sight vocabulary development, including to her
own name. She learned to write imaginatively employing phonetically true spelling
but cannot read what she has written. Her progress and the difficulties
encountered during the management of her condition are discussed in this first
case report of the evolution of pure alexia without agraphia in childhood. The
features of this syndrome in the developing child who has never developed the
capacity to read are contrasted with that seen in affected adults.
PMID- 9652785
TI - Bilateral oedema of the basal ganglia in an echovirus type 21 infection: complete
clinical and radiological normalization.
AB - A 4-year-old girl with bilateral striatal oedema in association with an echovirus
type 21 infection is reported. In the course of a prolonged upper respiratory
tract infection, the patient developed muscular hypotonia, resting tremor,
ataxia, sleepiness, hyperaesthesia, and indistinct speech. T2-weighted cranial
MRI revealed bilateral oedema of the basal ganglia and the cerebellar peduncles.
At follow-up after 3 months MRI changes and clinical symptoms had fully resolved.
PMID- 9652786
TI - Juvenile familial amyotrophic lateral sclerosis: four cases with long survival.
AB - Four cases are reported of juvenile familial amyotrophic lateral sclerosis
(JFALS) with exceptionally long survival (mean=27 years), and consequent
development of dementia. Subjects' mean age at onset was 15.7 years. Their
clinical features and electrophysiological findings support the diagnosis. One
subject's MRI scan showed severe atrophy to the cortex and brain stem; wallerian
degeneration in the pyramidal pathway, as reported in other studies, could not be
found. JFALS is characterized by the involvement of other neuronal systems not
present in the adult form and by long survival after disease onset.
PMID- 9652787
TI - Changes in liver fatty acid-binding protein in rat enzyme-altered foci.
AB - The level of liver fatty acid-binding protein (L-FABP) was analyzed in enzyme
altered foci (EAF) positive for GST-P, or after classification of foci into
different subclasses by haematoxylin and eosin staining. Rats were treated with
either an initiating single dose of diethylnitrosamine (DEN) followed by no
treatment, treatment with phenobarbital, PCB, nafenopin or repeated injections of
DEN, or alternatively non-treated or treated with nafenopin alone. Changes in the
level of L-FABP were detected in the majority of EAF and both L-FABP-positive and
-negative foci were seen. However, in rats initiated with DEN, EAF were almost
exclusively L-FABP-negative. The fraction of L-FABP-negative foci increased with
increasing foci size, while the time of treatment or the dose of the promoter did
not seem to have any effect. It was also found that treatment with DEN gave a
higher fraction of L-FABP-negative foci as compared to treatment with
phenobarbital or PCB, indicating a specific effect of DEN. These data together
with previously published findings suggest that L-FABP expression in EAF is
determined by the initiating carcinogenic regimen and that it might be possible
to use the expression of L-FABP in tumours to differentiate initiating chemicals.
PMID- 9652788
TI - Caspase proteases mediate apoptosis induced by anticancer agent preactivated
MC540 in human tumor cell lines.
AB - The molecular events involved in tumor cell death induced by novel photoproducts
of merocyanine 540 (pMC540) are poorly understood. Using HL60 leukemia and M14
melanoma cell lines we investigated the role of the apoptotic pathway in pMC540
mediated cell death. Tumor cells exposed to pMC540 showed cell size shrinkage and
an increase in the sub-diploid DNA content. A loss of membrane phospholipid
asymmetry associated with apoptosis was induced by pMC540 in both tumor cell
lines as evidenced by the externalization of phosphatidylserine. A dose-dependent
increase in caspase-3 protease activity suppressed by the tetrapeptide inhibitor
DEVD-CHO was observed in both cell lines. Western blot analysis of poly (ADP
ribose) polymerase, a caspase substrate, showed the classical cleavage pattern
(116 to 89 kDa) associated with apoptosis in pMC540-treated cell lysates.
Furthermore, caspase inhibition blocked the externalization of membrane PS,
indicating that the loss of membrane phospholipid asymmetry is a downstream event
of caspase activation. These findings demonstrate that tumor cell death induced
by pMC540 is mediated by caspase proteases.
PMID- 9652789
TI - Distant metastasis of gastric cancer is associated with elevated expression of
the antimetastatic nm23 gene.
AB - To understand the clinical significance of nm23 gene expression in gastric cancer
patients, the Nm23-H1 protein level of fresh resected specimens from a total of
37 gastric cancer patients was measured by Western blot analysis. The elevated
nm23 expression group (Nm23-H1 protein level in tumor tissue greater than the
75th percentile value of patients) was significantly associated with the
histologically differentiated type (P = 0.036). This group had a higher incidence
of distant (hematogeneous) metastasis (P = 0.0023) and a lower 2-year disease
free survival rate (P = 0.033) than the non-elevated group. The result was not
consistent with the previous assumption that nm23 is an antimetastatic gene for
gastric cancer.
PMID- 9652790
TI - Glutathione S-transferase-placental form expression and proliferation of
hepatocytes in fumonisin B1-treated male and female Sprague-Dawley rats.
AB - Fumonisin B1 (FB1), a mycotoxin produced by a common corn contaminant Fusarium
moniliforme and a hepatocarcinogen in rats, has been previously suggested to act
as a poor initiator, but a better promoter of gamma-glutamyltranspeptidase (GGT)
positive rat liver preneoplastic lesions. Using glutathione S-transferase
placental form (GSTP) as a more sensitive marker of initiation, we have further
evaluated the initiating capacity of various doses of purified FB1 administered
(a) intraperitoneally (i.p.) to male Sprague-Dawley (SD) rats for 4 days and (b)
orally (PO) to male and female SD rats for 11 days. Compared to their respective
controls, significant increases in GSTP-positive hepatocytes were observed in
male rats administered FB1 i.p. at 10 mg/kg body weight/day for 4 days, as well
as in male and female rats treated with 35 and 75 mg/kg body weight/day FB1 p.o.
for 11 days. The percentage section area of liver occupied by GSTP-positive mini
foci comprising of three to 12 cells was increased significantly in male rats
given 10 mg/kg FB1 i.p., or in p.o.-treated males and females with 75 mg/kg FB1.
Both i.p. and p.o. FB1 treatments resulted in dose-related enhanced hepatocyte
proliferation as measured by proliferating cell nuclear antigen (PCNA) labeling
with significant increases in the number of PCNA-positive nuclei at the same i.p.
and p.o. dose levels where the number of GSTP-positive cells were elevated. In
all studies, enhanced PCNA and GSTP expression occurred at FB1 doses which, based
on serum biochemical and histopathological data previously reported from our
laboratory, were shown to be hepatotoxic. Therefore, our data suggest that in a
manner similar to known genotoxic carcinogens, FB1 has the capacity to initiate
GSTP-positive hepatocytes with their subsequent development into GSTP mini-foci
at exposure levels that induce enhanced hepatocyte proliferation in response to
liver toxicity. In SD rats, this occurs as early as within 4 days of i.p.
treatment or 11 days of p.o. treatment.
PMID- 9652791
TI - Insulin-like growth factor II (IGF-II) secreted from HepG2 human hepatocellular
carcinoma cells shows angiogenic activity.
AB - Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Since insulin
like growth factor II (IGF-II) has been reported to play a significant role in
liver regeneration and hepatocarcinogenesis, we initially examined its angiogenic
effect on the chorioallantoic membrane (CAM) of 9-day-old chick embryos. We also
investigated whether IGF-II secreted from HepG2 human hepatocellular carcinoma
cells induces vascularization using the chick embryo CAM. We found that the
concentrated conditioned media (CCM) of HepG2 cell culture induced angiogenesis
on the CAM. We also identified IGF-II protein in the CCM from HepG2 cells by
Western blot analysis. However, CCM from Chang liver cells, which are normal
human liver cells and were free of IGF-II, did not induce angiogenesis in the
CAM. These results suggest that IGF-II secreted from hepatocellular carcinoma
cells may act as an angiogenic factor for the hypervascularization of HCC.
PMID- 9652792
TI - Loss of tumorigenicity of human pancreatic carcinoma cells engineered to produce
interleukin-2 or interleukin-4 in nude mice: a potentiality for cancer gene
therapy.
AB - To examine the possibility of cytokine gene therapy in relation to pancreatic
cancer, we evaluated the antitumor effect of human pancreatic carcinoma cells
(AsPC-1) which were retrovirally-transduced with several kinds of cytokine genes.
These cells were inoculated into BALB/c nude mice and their tumor volumes were
assessed. The in vitro growth rate of the transduced cells was not different from
that of a parental cell line. Among the transduced cells, human interleukin (IL)
6-transduced AsPC-1 and mouse granulocyte macrophage colony-stimulating factor
transduced AsPC-1 cells showed a significant retardation of tumor growth compared
with a parental cell line. In the cases of AsPC-1 cells transduced with the human
IL-2 or mouse IL-4 gene, small tumors were generated but thereafter they
regressed completely. Histological examinations showed monocytic cell
infiltration around the tumors of IL-2- or IL-4-producing cells. These data
suggest that secretion of IL-2 or IL-4 from tumor cells can induce an antitumor
effect even in the defective condition of mature T cells.
PMID- 9652793
TI - Platelet-derived endothelial cell growth factor/thymidine phosphorylase
expression correlated with tumor angiogenesis and macrophage infiltration in
colorectal cancer.
AB - To clarify whether platelet-derived endothelial cell growth factor/thymidine
phosphorylase (PD-ECGF/TP) expression in both tumor cells and stromal cells has
independent or synergistic effects on tumor angiogenesis and progression and to
explore a possible regulator for PD-ECGF/TP expression, immunohistochemical
staining was conducted on 148 specimens of colorectal cancer. The microvessel
count was significantly correlated with the extent of PD-ECGF/TP expression.
Macrophage infiltration in tumors with positive TP was significantly higher than
in tumors with negative TP (P < 0.001). The Cox model showed that PD-ECGF/TP
expression was an independent prognostic factor, although the microvessel count
had a stronger value in determining the patient prognosis.
PMID- 9652794
TI - Human melanoma metastasis is inhibited following ex vivo treatment with an
antisense oligonucleotide to protein kinase C-alpha.
AB - To determine whether alteration of PKC alpha expression would affect the
metastatic potential of human melanoma cells, replicate cultures of C8161 cells
were treated in vitro with a phosphorothioate antisense oligodeoxynucleotide
(ODN) that specifically inhibits PKC alpha expression (ISIS-3521). Control C8161
cultures were treated with a scrambled sequence ODN, cationic liposomes or were
left untreated. Northern blots demonstrated 70% inhibition of PKC alpha mRNA in
ISIS-3521-treated cells compared to controls. Metastasis was suppressed by 75%
when ISIS-3521-treated cells were injected intravenously into athymic mice. These
results show that PKC alpha expression is important in the regulation of human
melanoma metastasis.
PMID- 9652795
TI - A model of wound healing in chronically radiation-damaged rat skin.
AB - The aim of this investigation was to develop a model for studying the chronic
effects of radiation on wound healing in the rat. Six months after rats received
a single radiation exposure of 20 Gy, a random-pattern dorsal skin flap was
elevated. Two weeks after the flap was elevated, irradiated animals showed
diminished scar formation and wound breaking strength, as compared with controls
(P < 0.05). The effect of hyperbaric oxygen treatment was investigated in some
rats who received 20 sessions at 2.4 atmospheres absolute for 90 min daily, 5
days per week, prior to flap elevation and 10 sessions after creation of the
flap. Treated animals showed a trend toward improvements in wound breaking
strength and scar formation (P = 0.06). A reproducible model of chronic radiation
damage in the rat was established. Further studies involving investigations at
times more that 2 weeks post-wounding are needed.
PMID- 9652796
TI - Kinetics of the inhibition of acetylcholinesterase in camel retina by cisplatin.
AB - The inhibitory effect of cisplatin (CDDP) on camel retina acetylcholinesterase
(AChE) was characterized. The CDDP effect was independent of the time of
incubation with AChE before the addition of substrate, indicative of reversible
inhibition. Moreover, dilution data prove that CDDP is a reversible inhibitor of
camel retina AChE. Cisplatin inhibited AChE activity of camel retina in a
concentration- and time-dependent manner, the IC50 values being 5.32 and 0.196 mM
at 5 min and 24 h incubation times, respectively. The IC50 has dual components,
i.e. directly proportional and inversely proportional to 0-1.5 h and 1.5-24 h
incubation periods, respectively. The Michaelis-Menten constant (Km) for the
hydrolysis of acetylthiocholine iodide (ASCh) was found to be 0.0796 mM and Vmax
was 0.668 micromol/min/mg protein. Kmapp and Vmaxapp both decreased as the CDDP
concentration increased. Dixon as well as Lineweaver-Burk plots and their
secondary replots indicated that the nature of the inhibition was of the pure
uncompetitive type. The value of Ki was estimated as 0.811 mM by the primary and
secondary replots of the Lineweaver-Burk and Dixon plots. Kiapp decreased while
Vmaxiapp increased after increasing the ASCh concentration.
PMID- 9652797
TI - Variable Bcl-2 phenotype in benign and malignant lesions of urothelium.
AB - We examined Bcl-2, Bax and p53 expression in transitional epithelium, benign
lesions derived from transitional epithelium (Brunn's nests and inverted
papillomas) and transitional cell cancer (TCC) of the upper urinary tract and
urinary bladder using immunostaining of cryostat sections. We also performed
Western blot analysis of normal urothelium and TCCs for Bcl-2 and p53.
Immunohistochemical staining showed that Bcl-2 was expressed only on basal layer
cells, whereas Bax expression was restricted to superficial layers in normal
transitional epithelium. Benign lesions of the urinary bladder (Brunn's nests and
inverted papillomas) showed strong immunoreactivity to Bcl-2. Taken together, 16
(17%) TCCs were positive for Bcl-2, 62 (64.6%) TCCs were positive for Bax and 28
(29%) TCCs were positive for p53. The expression of Bcl-2 on TCC had a
statistical correlation with tumor stage, histopathologic grade and p53 protein
accumulation. The results suggest that although Bcl-2 overexpression is detected
in normal urothelium and benign lesions of the urinary bladder, it might also
contribute to the high grade tumor malignancy of TCC.
PMID- 9652798
TI - Prognostic value of mutations and a germ line polymorphism of the p53 gene in non
small cell lung carcinoma: association with clinicopathological features.
AB - The prognostic value of the mutation of the p53 tumor suppressor gene in non
small cell lung carcinomas (NSCLC) is controversial and a polymorphism of the p53
gene at codon 72 consisting of two alleles, arginine (Arg) and proline (Pro), has
been reported to be associated with the incidence of smoking-related NSCLC. We
have studied 67 cases of NSCLC in relation to the mutation of the p53 gene by
polymerase chain reaction (PCR)-single-strand conformation polymorphism and 178
cases in relation to the polymorphism of the gene by PCR using allele-specific
primers. The genetic alterations of the p53 gene (from exons 5 to 9) were found
in 34% of the patients. Frequent mutations were observed among younger patients
(less than 65 years old), however, there is no significant correlation of the
mutation with smoking history, histopathological types, clinical stages or
prognosis. We observed that Arg/Arg homozygotes were frequently found in non
smoking patients with NSCLC but Arg/Pro heterozygotes were infrequent in the
group. There was no significant association of the polymorphic alleles with
histopathological types, clinical stages or prognosis. Thus, the polymorphism of
the p53 gene affects the predisposition of non-smokers to NSCLC, but the
alteration of the p53 gene is independent of tumor progression and
histopathology.
PMID- 9652799
TI - Tumour necrosis factor-alpha does not cross the rat placenta.
AB - In the last few years there has been a considerable proliferation of studies
suggesting that tumour necrosis factor-alpha (TNF) has a very important
physiological role in pregnancy. Its presence in the fetus has been related to
several important roles such as cell growth and differentiation or immune
protection. The aim of the present work was to analyze whether maternal TNF could
reach the fetal circulation. The results found after in vivo [125I]TNF
administration to pregnant rats at term demonstrate that, TNF does not cross the
placenta and therefore it may be suggested that the cytokine which is found in
the fetus is synthesized in its organs.
PMID- 9652800
TI - Resistance factors in colon cancer tissue and the adjacent normal colon tissue:
glutathione S-transferases alpha and pi, glutathione and aldehyde dehydrogenase.
AB - Glutathione S-transferases (GST) alpha and pi, glutathione (GSH) and aldehyde
dehydrogenase (ADH) were determined in colorectal cancer tissue specimens and in
the adjacent normal colon tissue. The median contents in normal and cancer tissue
were 8.1 (2.3-30.3) (5-95% quantiles) and 15.1 (5.3-50.3) microg/mg protein for
GST pi (P = 0.035), 0.0 (0.0-1.4) and 0.4 (0.0-3.5) microg/mg protein for GST
alpha (P = 0.019), 7.3 (1.3-22.7) and 5.6 (2.3-26.0) microg/mg protein for GSH (P
= 0.171) and 30.8 (13.0-42.0) and 23.2 (9.0-32.9) microg/mg protein for ADH (P =
0.0017), respectively. Thus, the mean GST alpha and pi both significantly
increased in colon cancer compared to the adjacent normal tissue, which
underlines their importance as possible resistance factors. A highly significant
correlation was obtained between the GSH content in colon cancer and normal
tissue (P = 0.0017). Thus, the constitutive GSH expression seems to be maintained
during tumor development. A similar correlation was obtained for ADH (P =
0.0075), but the median ADH was lower in cancer tissue compared to the adjacent
normal tissue (P = 0.0017). Contrary to GSH and ADH, GST pi did not correlate
between normal and colon cancer tissue. Whereas GSH and ADH correlated in normal
colon tissue (P = 0.014), no significant correlation for GSH and ADH was observed
in colon cancer tissue (P = 0.109). In conclusion, significant correlations
between colon cancer and normal tissue were obtained, suggesting that the
expression levels of these resistance factors are maintained during
carcinogenesis in most patients.
PMID- 9652801
TI - Human in vitro cell lines verification by minisatellite DNA restriction fragment
length polymorphism.
AB - Four families of human in vitro cell lines were tested for minisatellite
restriction fragment length polymorphism (RFLP) using multilocus probes MZ1.3
and/or 33.15 after digestion of DNA with restriction enzymes HinfI or HaeIII.
These results confirmed that (i) the RFLP pattern is relatively stable in
established cell lines and, therefore, could be used as a specific marker of a
cell line identity, (ii) the use of MZ1.3 and 33.15 probes permits the
identification of hybridomas and (iii) one of the cell lines tested, a
lymphoblastoid cell line HAJ, may possess a hot spot of mutation.
PMID- 9652802
TI - Mechanisms of induction of apoptotic DNA fragmentation.
AB - PURPOSE: Despite its common use as an indicator of apoptosis, little is known
about the mechanisms controlling apoptotic DNA fragmentation in irradiated cells.
This review discusses the pathways of chromatin fragmentation, and the role of
both nucleases and chromatin structure in this process. DEFINITIONS: DNA
fragmentation linked to apoptosis is a combination of cleavage events excising
both large DNA fragments within the range 0.4-1.0 Mbp and 50 kbp followed by
random cuts within internucleosomal regions (i.e. DNA laddering). The first two
cleavage steps can be detected in virtually all apoptotic cells, but DNA
laddering is not ubiquitously observed. Endonucleases that mediate this cleavage
of chromatin may be classified by substrate specificity, mode of DNA cleavage and
their cofactor requirements. CONCLUSIONS: Three major pathways of DNA
fragmentation are proposed and discussed: (1) upregulation of endonucleases, (2)
their intranuclear/intracellular redistribution and (3) primary changes of
chromatin structure.
PMID- 9652804
TI - On the experimental distinction between ssbs and dsbs in circular DNA.
AB - PURPOSE: To determine directly the minimal distance between two ssbs on
complementary strands in circular DNA that are not observed as a dsb by
electrophoresis. MATERIALS AND METHODS: 3.2 kbp DNAs with cohesive overhangs of
various lengths were systematically generated by a newly devised method and
electrophoresed in agarose slabs. RESULTS: At 4 degrees C, 3.2 kbp DNA with
cohesive overhangs larger than 6 bp migrated as circular DNA. The minimal
overhang size for the DNA to migrate as circular DNA was larger at 25 degrees C.
Whether the DNA migrated as a circular or a linear molecule depended also on the
nucleotide sequence of its overhangs, most notably at the minimal size.
CONCLUSIONS: The minimal distance obtained in the present study agrees with the
smaller values of previous indirect estimates. The dependence of the distance on
experimental conditions suggests feasibility of obtaining the stagger-size
distribution of radiation-induced dsbs.
PMID- 9652803
TI - Reduced joining of DNA double strand breaks with an abnormal mutation spectrum in
rodent mutants of DNA-PKcs and Ku80.
AB - PURPOSE: To characterize further the contribution of the DNA-PK-dependent dsb
repair pathway in mammalian cells. MATERIALS AND METHODS: The efficiency and
fidelity of the joining of linear plasmids by DNA-PKcs-defective mouse cells
(SCID) and Ku80-defective Chinese hamster ovary cells (xrs-6) was measured using
either linear or circular replicating shuttle vector pZ189. RESULTS: The authors
found a 3.9-10.7-fold reduced joining of the DNA ends, as compared with wild-type
cells. Mutation analysis of the joining site revealed that the joining process
was not hypermutable in the mutated cells. However, the SCID and xrs-6 cells
produced a different spectrum of mutations at the joining site with a
significantly lower proportion of insertions or more complex mutations.
CONCLUSIONS: The remaining joining ability of the mutant cells points to an
alternative DNA-PK-independent pathway of dsb repair. Comparison of these data
with similar data from yeast suggest that the postulated alternative pathway of
dsb repair is at least as efficient and less error-prone in rodent cells.
PMID- 9652805
TI - In vitro rejoining of DNA double strand breaks: a comparison of genomic-DNA with
plasmid-DNA-based assays.
AB - PURPOSE: To evaluate potential similarities between the enzymatic activities
required to rejoin DNA double strand breaks (dsb) in an in vitro assay based on
genomic DNA and an in vitro assay based on plasmid DNA. Because the latter assay
is simpler and faster, it should be preferred for the characterization of repair
factors if both assays are found to probe for the same activities. If, however,
the enzymatic requirements for dsb rejoining are different between the two
assays, both should be used as they are likely to play complementary roles in the
characterization of repair factors. MATERIALS AND METHODS: A cell-free assay has
been used, developed to study rejoining DNA dsb induced by radiation in 'naked'
DNA prepared from agarose embedded cells using an extract of HeLa cells as a
source of enzymes. Also employed was an in vitro assay using the ligation of
linearized plasmid DNA to model dsb rejoining. RESULTS: Evidence is presented
that, under the conditions employed, different sets of activities are involved in
the ligation of linearized plasmid DNA and in the rejoining of dsb in 'naked'
genomic DNA. Optimal rejoining of dsb induced in genomic DNA is observed with
cytoplasmic cell extract at 37 degrees C, whereas optimal ligation of plasmid DNA
is observed with nuclear extract at 25 degrees C. Rejoining of dsb in genomic DNA
comes to a near halt at 14 degrees C, but plasmid DNA ligation proceeds at
significant rates at this temperature. Furthermore, the activities required for
the rejoining of dsb induced in genomic DNA are partly stable to heating at 50
degrees C for 1 h, whereas activities required for the ligation of plasmid DNA
are completely inactivated by a similar treatment. Both reactions require ATP for
optimal performance, and in both, DNA joining is inhibited at high ATP
concentrations. CONCLUSIONS: These observations indicate that the plasmid-and the
genomic-DNA-based assays probe for, at least partly, different sets of activities
and therefore are expected to play complementary roles in the purification and
characterization of activities involved in dsb rejoining.
PMID- 9652806
TI - DNA damage induction and tumour cell radiosensitivity: PFGE and halo
measurements.
AB - PURPOSE: To test whether induction of DNA damage is correlated with tumour-cell
radiosensitivity. MATERIALS AND METHODS: Initial DNA damage caused by X
irradiation was measured in ten human tumour cell lines, which largely differed
in radiosensitivity, using either the pulsed-field gel electrophoresis assay or
the halo technique. RESULTS: None of the parameters of DNA damage correlated with
any parameter of cellular radiosensitivity. This was not only true when the
analysis was performed on all data but also when the analysis was performed after
separating the cell lines into radioresistant and sensitive groups. Even when
differences in chromosome number, ploidy and cell cycle distribution were taken
into account, no significant correlations were obtained. CONCLUSIONS: Contrary to
previous suggestions, differences in the number of double-strand breaks induced
or chromatin-related 'presentation' of DNA lesions, measured by pulsed-field gel
electrophoresis or halo respectively, are generally not the dominant factors
determining tumour-cell radiosensitivity.
PMID- 9652807
TI - Apoptosis induced by X-rays and chemical agents in murine fibroblastic cell lines
with a defect in repair of DNA double-strand breaks.
AB - PURPOSE: To investigate apoptosis in murine fibroblasts that are deficient in DNA
double-stand breaks (dsb) repair. MATERIALS AND METHODS: BALB/c 3T3 cells and
cells from a severe combined immunodeficient (scid) mouse were exposed to X-rays,
UV light, bleomycin, etoposide or cisplatin. After exposure, the rate of
apoptosis was assayed by propidium iodide staining based on characteristic
morphological change. RESULTS: The scid cells, defective in dsb repair, were
extremely sensitive to apoptosis induced by X-rays and bleomycin compared with
BALB/c 3T3 cells. The scid cells were slightly sensitive to apoptosis induced by
etoposide, an agent producing protein-associated dsb, and to apoptosis induced by
agents not causing dsb. CONCLUSIONS: These studies show that sensitivity of cells
to apoptosis induced by X-rays or bleomycin is enhanced by the scid mutation and
that apoptosis induced by etoposide, which causes protein-associated dsb, is not
greatly affected. There may be different processes involved in the induction of
apoptosis by X-rays or bleomycin and etoposide.
PMID- 9652808
TI - Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine
(dFdC), two nucleoside analogues, is not mediated by an increased induction or a
repair inhibition of DNA double-strand breaks as measured by pulsed-field gel
electrophoresis.
AB - PURPOSE: To investigate the effect of fludarabine (F-ara-A) and gemcitabine
(dFdC), two radiosensitizing nucleoside analogues, on the induction and repair of
DNA dsb after ionizing radiation. MATERIALS AND METHODS: Radiosensitization of
mouse sarcoma SA-NH and FSA cells was studied using a clonogenic assay. Cell
survival curves were fitted with the linear-quadratic model. DNA dsbs were
detected by pulsed-field gel electrophoresis under neutral conditions. RESULTS: F
ara-A (100 micromol dm(-3) for 1 h prior to irradiation) induced a substantial
radiosensitization in SA-NH cells with a dose modification factor of 2.0 for a
surviving fraction of 0.5. In a FSA mouse sarcoma cell line, dFdC (5 micromol dm(
3) for 3 h prior to irradiation) induced a modest radiosensitization with a DMF
of 1.2 for a surviving fraction of 0.5. Under similar experimental conditions,
neither F-ara-A nor dFdC altered the yield of radiation-induced DNA dsbs in the
dose range of 0-40 Gy. After a single dose of 25 Gy (SA-NH cells) or 40 Gy (FSA
cells), neither the kinetics of repair nor the amount of residual damage was
affected by F-ara-A or dFdC. CONCLUSIONS: For experimental conditions under which
radiosensitization was observed, neither the induction nor the repair of DNA dsbs
after ionizing radiation were affected by F-ara-A or dFdC.
PMID- 9652809
TI - Estimate of true incomplete exchanges using fluorescence in situ hybridization
with telomere probes.
AB - PURPOSE: To study the frequency of true incomplete exchanges in radiation-induced
chromosome aberrations. MATERIALS AND METHODS: Human lymphocytes were exposed to
2 Gy and 5 Gy of gamma-rays. Chromosome aberrations were studied using the
fluorescence in situ hybridization (FISH) technique with whole chromosome
specific probes, together with human telomere probes. Chromosomes 2 and 4 were
chosen in the present study. RESULTS: The percentage of incomplete exchanges was
27% when telomere signals were not considered. After excluding false incomplete
exchanges identified by the telomere signals, the percentage of incomplete
exchanges decreased to 11%. Since telomere signals appear on about 82% of the
telomeres, the percentage of true incomplete exchanges should be even lower and
was estimated to be 3%. This percentage was similar for chromosomes 2 and 4 and
for doses of both 2 Gy and 5 Gy. CONCLUSIONS: The percentage of true incomplete
exchanges is significantly lower in gamma-irradiated human lymphocytes than the
frequencies reported in the literature.
PMID- 9652810
TI - Non-fluorescent chromosome painting using the peroxidase/diaminobenzidine (DAB)
reaction.
AB - PURPOSE: To develop and validate non-fluorescent chromosome painting for bright
field microscopy using the peroxidase/diaminobenzidine (DAB) reaction. MATERIALS
AND METHODS: Peripheral blood lymphocytes were taken from patients with uterine
cancer who had received heavy-ion radiation therapy. Chromosome slides were
treated with RNase and pepsin, denatured mildly, hybridized with a biotinylated
DNA probe specific for whole-chromosome 4 and stained using the peroxidase/DAB
reaction with an avidin-biotin amplification. The slides were analysed under a
bright-field microscope and an atomic force microscope. The detection rate of
chromosome aberrations by DAB painting was compared with that obtained by dual
analysis of Giemsa staining and FISH painting. RESULTS: When chromosomes 4 were
painted, 11.5% of unstable aberrations were detected by DAB painting, while 10.8%
of them were found by dual analysis of Giemsa staining and FISH painting.
CONCLUSION: A DAB painting method that can effectively detect rearranged
aberrations was established. It has advantages over FISH painting: the
preparations can be analysed by bright-field microscope, can be preserved
permanently and are suitable for analysis by an automated system.
PMID- 9652811
TI - Oral administration of tritiated water (HTO) in mouse. III: Low dose-rate
irradiation and threshold dose-rate for radiation risk.
AB - PURPOSE: To investigate the biological effect of tritium on mouse at low dose
rates. MATERIALS AND METHODS: Mice ([C57BL/6N x C3H/He]F1) were exposed to beta
rays by continuous administration of tritiated drinking water throughout their
lives at low dose-rates of 3.6, 0.9, and 0.2 mG/day. RESULTS: Including the
previous study, the tumour frequency was 70 to approximately 80% for exposure in
the range 240 mGy/day to 9.6 mGy/day. Frequency of tumours decreased with
decrease of dose-rate to 50% comparable to the controls. Restricting to thymic
lymphomas, a linear relationship in a semi-log plot was found between the
frequency and the dose-rate above a threshold dose-rate of 12 mGy/day. There was
a 'tail' to this relationship down to 0.9 mGy/day. A similar pattern resulted for
the relationship between the life-shortening and the dose-rate. The threshold
dose-rate of 3H beta-rays, 2 mGy/day (with a tail down to 0.2 mGy/day), was much
lower than that of gamma-rays, 20 mGy/day (tail down to 2 mGy/day) derived from
other studies. CONCLUSIONS: These studies suggest that there exists the threshold
dose-rate in the biological effects of radiation, and that the threshold dose
rate for 60Co gamma-irradiation is higher than that for 3H beta-irradiation.
PMID- 9652812
TI - Accidental intake of tritiated water: a cytogenetic follow-up case on
translocation stability and dose reconstruction.
AB - PURPOSE: To examine by fluorescence in situ hybridization (FISH) chromosomal
translocations in a person who, 11 years previously, had accidentally
incorporated tritiated water. To compare the resultant estimate of radiation dose
with contemporary dosimetry made by urine analysis and dicentric chromosome
scoring. MATERIALS AND METHODS: Blood lymphocytes were shared by two laboratories
each performing the FISH analysis using different chromosome probe combinations.
Doses were calculated by reference to an in vitro calibration curve produced in
one of the laboratories. RESULTS: Good agreement in translocation yields was
found by the two laboratories. Comparing the yields with the dicentric frequency
obtained shortly after the accident and with a translocation frequency measured 6
years post exposure showed good agreement between all measurements. This
indicates essentially perfect stability for translocations over an 11 year period
in this individual. CONCLUSIONS: Dose reconstruction based on FISH-measured
translocations showed good agreement with the dose estimated from initial
dicentric measurements and from measurements of tritium in urine. Because of the
extensive initial dosimetry performed on this individual, who received a uniform
whole-body irradiation, the case serves as an excellent test for the use of FISH
measured translocations for retrospective biodosimetry.
PMID- 9652813
TI - Micronucleus frequencies in cytokinesis-blocked human B lymphocytes after low
dose gamma-irradiation.
AB - PURPOSE: To investigate (1) the radiosensitivity of B versus T lymphocytes with
respect to micronucleus (MN) induction and (2) the possible application of the B
cell MN assay for biological dosimetry of individuals after acute exposure to low
doses of ionizing radiation. MATERIALS AND METHODS: MN analysis was performed in
T and B lymphocytes of six healthy volunteers exposed in vitro to gamma-ray doses
ranging from 0.05 Gy to 1 Gy. For the MN assay on B cells, peripheral blood
mononuclear cells were cultured and stimulated with pokeweed mitogen (PWM).
Afterwards the B lymphocytes (characterized by the CD20+ phenotype) were
separated with the FACSort flow cytometer and the number of MN in the sorted
binucleate cells was scored. For T lymphocytes the standard MN protocol was
applied. RESULTS: The number of spontaneous and radiation induced MN were
significantly higher in B lymphocytes compared to T lymphocytes in the low dose
range up to 1 Gy. An analysis of the present data showed that when the
spontaneous MN frequencies are not known, doses from 0.08 Gy could be detected
with the B cell MN assay while the conventional MN assay only allowed detection
of doses > 0.25 Gy. However, in contradiction to the linear-quadratic dose
response for T cells, for B cells the initial steep increase of the MN yield with
the very low dose was followed by a flattening of the curve towards higher doses.
CONCLUSION: This study shows that B lymphocytes express a high number of MN for
doses up to 1 Gy gamma-rays reflecting the highly radiosensitive behaviour of B
cells. The results also point to the possible application of the B-cell MN assay
for individual dose assessment. When blood samples can be taken within 24 h after
acute accidental overexposure, the B-cell MN assay can be performed but only as a
supplementary test to the conventional MN assay.
PMID- 9652814
TI - Irradiation of Crotalus durissus terrificus crotoxin with 60Co gamma-rays induces
its uptake by macrophages through scavenger receptors.
AB - PURPOSE: To investigate the action of 2 kGy 60Co gamma-rays on crotoxin and its
favoured uptake through scavenger receptor (ScvR) mouse peritoneal macrophages.
MATERIALS AND METHODS: Native or irradiated crotoxin (iCTX) (50 microg/ml) dosed
with 2 kGy 60Co gamma-rays (dose-rate 540 Gy/h) were offered to mouse peritoneal
macrophages; their uptake was evaluated by immunohistochemistry and quantitative
in situ ELISA. Receptors recognizing irradiated crotoxin were evaluated with
specific ScvR blockers (Probucol and dextran sulphate) or with non-specific
blocking using foetal calf serum (FCS). RESULTS: Immunohistochemical assays
revealed more deeply staining intracytoplasmic vacuoles in macrophages incubated
with iCTX. Using in situ ELISA with ScvR specific blockers, it was shown that the
increased uptake of iCTX was blocked by Probucol or dextran sulphate, but not by
FCS. On the other hand, the uptake of native crotoxin was decreased by FCS, but
not affected by ScvR blockers. The morphology and viability of macrophages were
preserved during the experiments. CONCLUSIONS: It is concluded that 60Co gamma
rays probably induced oxidative changes in crotoxin, driving this toxin towards
ScvR mouse peritoneal macrophages. This suggests a different in vivo route of
iCTX away from toxic neural sites by a preferential and rapid internalization and
processing by macrophages, leading to the induction of a better immune response.
PMID- 9652815
TI - Labelling of bleomycin with Auger-emitter increases cytotoxicity in squamous-cell
cancer cell lines.
AB - PURPOSE: To investigate the cytotoxicity of bleomycin (BLM), two Auger-emitting
bleomycin complexes (indium-111 ((111)In)-BLMC) and (111)InCl3 in three squamous
cell cancer (SCC) cell lines. MATERIAL AND METHODS: Three recently established
SCC cell lines were investigated using the 96-well clonogenic assay.
Concentrations causing 50% inhibition in cell survival (IC50) were calculated for
BLM and two specific activities of (111)In-BLMC (40 MBq/mg BLM (low) and 195
MBq/mg BLM (high)). RESULTS: (111)In-BLMC (low) was the most toxic to the SCC
cell lines. (111)In-BLMC containing 4.9-fold more activity of (111)In (195 MBq/mg
BLM) was more effective than BLM (p=0.0029), but not as toxic as (111)In-BLMC
(low) (p=0.0023). UT-SCC-19A had a IC50 value for BLM as low as 4.1 nM, whereas
IC50 values for (111)In-BLMC (low) and (111)In-BLMC (high) were 2.0 nM and 2.6
nM, respectively. The most chemoresistant cell line UT-SCC-12A had a IC50 value
for BLM of 18.8 nM, for (111)In-BLMC (low) 10.7 nM and for (111)In-BLMC (high)
12.7 nM. (111)InCl3 had no cell killing effect. CONCLUSIONS: This study shows
that (111)In-BLMC is superior in SCC cell killing compared with BLM. These data
provide the basis for further clinical investigations of (111)In-BLMC.
PMID- 9652816
TI - Comment on the paper: Quantifying the position and steepness of radiation dose
response curves.
PMID- 9652817
TI - Comments on the paper: Cell survival in irradiated microcolonies: how influential
are the neighbours?
PMID- 9652818
TI - Comment on the paper: High-voltage overhead lines and radon daughter deposition.
PMID- 9652819
TI - Dismantling in cell death: molecular mechanisms and relationship to caspase
activation.
AB - The notion of a cell death programme was introduced in view of the
reproducibility of its occurrence in time and space (e.g. in the developing
embryo) and of its genetic determination. Programmed cell death can be
schematically subdivided into three steps: a signalling phase, an execution phase
and a dismantling phase. This review focuses on the latter. Apoptosis is the most
studied form of dismantling of animal cells. The molecular pathways leading to
certain apoptotic lesions appear to be dependent on the proteolytic activity of
caspases. Death itself can, however, be caspase-independent. Also, non-apoptotic
forms of cell death exist, even in animal cells; their molecular bases are still
unknown. The relationship between cell death, apoptosis and caspases is
discussed.
PMID- 9652820
TI - Infiltration patterns of short- and long-term cultured A-NK and T-LAK cells
following adoptive immunotherapy.
AB - Direct contact between lymphokine-activated killer (LAK) cells and tumour cells
is believed to be imperative for initiating tumour cell lysis in vitro as well as
in vivo. In order to optimize adoptive immunotherapy (AIT) it is therefore
desirable to identify the LAK cell subtype, which ensures maximal infiltration of
tumours as well as a substantial cytotoxic reactivity. In this report we have
compared short- and long-term cultured murine adherent natural killer (A-NK)
cells and mitogen-stimulated, lymphokine-activated T-killer (T-LAK) cells with
respect to their proliferative potential, cytotoxicity, requirement for
interleukin-2 (IL-2) and ability to infiltrate B16 pulmonary metastases following
adoptive transfer. We found that short-term (5 days) cultured A-NK and T-LAK
cells both showed a substantial accumulation of tumour tissues. However, A-NK
cells gradually lost this ability during in vitro culture whereas T-LAK cells
cultured for as long as 20 days retained their ability to infiltrate metastases
as efficiently as their short-term cultured counterparts. Moreover, the low
requirement of IL-2 by T-LAK cells to achieve maximal infiltration of tumours
sharply contrasted with the excessive doses necessary to ensure maximal
infiltration by A-NK cells. In conclusion, these data demonstrate that short-term
cultured LAK cells of both NK- and T-cell origin are able to infiltrate B16
pulmonary metastases effectively. Importantly, the T cells retain this ability
for a considerably longer time and require much less IL-2 support than do A-NK
cells, making T-LAK cells attractive for AIT.
PMID- 9652821
TI - Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell
surface membrane induces rapid apoptosis of normal spleen B cells.
AB - Cross-linking of surface immunoglobulin (sIg) has been shown to induce either
activation or apoptosis of mature B cells presumably depending on the nature of
antigens. However, the nature of antigens for induction of mature B-cell
apoptosis is not yet fully understood. We cross-linked sIg of mature B cells with
various amounts of either anti-Ig antibodies in the soluble form or anti-Ig
coupled to erythrocytes or myeloma cells as surrogate membrane-bound antigens.
Anti-Ig antibodies coupled to cell surface membrane induced rapid and extensive
apoptosis of normal spleen B cells even in the absence of signalling via the Fc
receptor. In contrast, soluble anti-Ig induced proliferation or apoptosis of
mature B cells depending on the concentration of anti-Ig. The extent of apoptosis
induced by soluble anti-Ig was limited compared to that induced by membrane-bound
anti-Ig. These results suggest that mature B cells undergo apoptosis or
proliferation depending on whether antigens are soluble or membrane-bound and on
antigen doses.
PMID- 9652822
TI - Protective effect of beta-glucan against mycobacterium bovis, BCG infection in
BALB/c mice.
AB - Beta-1,3-glucan is a potent stimulator of macrophage functions and has a
protective effect against a range of infections in rodent models. We examined
whether the agent could also protect against the intracellular Mycobacterium
bovis, bacillus Calmette-Guerin (BCG) infection in mice. BCG-susceptible BALB/c
mice were injected intravenously (i.v.) with beta-glucan or vehicle 3 days
before, or with beta-glucan 7 days after i.v. challenge with live BCG bacilli.
The animals were killed 4 or 8 weeks later, their organs were homogenized and
applied to object slides and stained with auramin for counting of bacilli, or
seeded onto agar in Petri dishes. Mice treated with beta-glucan both pre- and
postchallenge had significantly lower numbers of BCG bacilli and BCG colony
forming units in spleen homogenates compared with controls 4 weeks after
challenge. A similar, but not statistically significant, tendency was observed in
spleen homogenates from mice killed 8 weeks after challenge. In homogenates of
liver and lungs there were similar findings, but less pronounced. There was a
dose-dependent effect of beta-glucan injected before BCG challenge on the number
of BCG bacilli found in spleen and liver homogenates. In addition, antibody cross
reactivity was demonstrated between M. tuberculosis cell wall and beta-glucan.
The results suggest that beta-glucan has a protective effect against M. bovis,
BCG infection in susceptible mice.
PMID- 9652823
TI - Expression of interferon-gamma, interleukin-4 and interleukin-5 mRNA in the nasal
mucosal membrane of rats with allergic rhinitis.
AB - The production of immunoglobulin E (IgE) antibody is largely dependent on the
ratio between interleukin-4 (IL-4) (a T helper 2 (Th2)-type cytokine) and
interferon-gamma (IFN-gamma) (a T helper 1 (Th1)-type cytokine). Interleukin-5
(IL-5) (also a Th2-type cytokine) is an important eosinophil differentiation
factor and also co-stimulates B-cell growth and differentiation. The present
study was designed to evaluate and compare the expression of IFN-gamma, IL-4 and
IL-5 mRNA in the nasal mucosal membrane of sensitized Brown-Norway (BN) rats.
Fourteen BN rats were divided into two groups: non-sensitized (control) and
sensitized. The sensitized group was injected with ovalbumin (OA)
intraperitoneally on three consecutive days. Twenty-one days later, rats were
exposed to 1% OA aerosol. Twenty-four hours after exposure to aerosol, nasal
mucosa was extracted from both groups and reverse transcriptase-polymerase chain
reaction (RT-PCR) was performed. The densities of the bands of IL-4, IL-5 and IFN
gamma mRNA were expressed as percentages against beta-actin mRNA. Our results
showed that the mean values for IL-4 and IL-5 mRNA were increased significantly
in sensitized rats compared with control rats. In contrast, the mean value for
IFN-gamma mRNA was significantly lower in sensitized rats compared with those of
the control group. Our data therefore suggest that sensitization of rat nasal
mucous membranes results in the predominant expression of Th2-type cytokines.
PMID- 9652824
TI - A peptide-binding assay for the disease-associated HLA-DQ8 molecule.
AB - The study of peptide binding to HLA class II molecules has mostly concentrated on
DR molecules. Since many autoimmune diseases show a primary association to
particular DQ molecules rather than DR molecules, it is also important to study
the peptide-binding properties of DQ molecules. Here we report a biochemical
peptide-binding assay for the type I diabetes-associated DQ8, i.e. DQ
(alpha1*0301, beta1*0302), molecule. Affinity-purified DQ8 molecules were tested
in peptide-binding assays using a radiolabelled influenza haemagglutinin (Ha)
peptide encompassing positions 255-271(Y) as an indicator peptide. The Ha 255
271(Y) peptide bound to DQ8 in a pH-dependent fashion showing optimal binding
around pH 5. The association kinetics were relatively slow and the resulting
complexes were heat labile. The specificity of peptide binding to DQ8 was
investigated in competitive inhibition experiments with a panel of 43 peptides of
different lengths and sequences. The DQ8 molecules showed a different pattern of
peptide binding compared to a previously studied DQ2 molecule. Peptides derived
from thyroid peroxidase, HLA-DQ(alpha1*0301), HLA-DQ(alpha1*0302), retinol
receptor and p21ras were among the high-affinity binders, whereas peptides
derived from myelin basic protein were among the low-affinity binders. The
sequence of the high-affinity peptides conformed with a previously published
peptide-binding motif of DQ8.
PMID- 9652825
TI - Immunoglobulin prolongs survival of pig kidneys perfused ex vivo with human
blood.
AB - Intravenous immunoglobulin (IVIG) (Octagam), was used to determine the effect on
hyperacute rejection in an ex vivo xenograft model. Six pig kidneys were perfused
with IVIG and fresh human AB blood, and six control pig kidneys were
simultaneously perfused with albumin and blood from the same donation. The
survival of the IVIG-perfused xenografts (median, 6.5 h) was significantly (P =
0.03) longer than the albumin-perfused xenografts (median, 3.5 h). Complement was
activated in both groups. The administration of IVIG to the perfused blood
resulted in immediate and significantly higher complement activation in the fluid
phase as compared with the albumin group. At rejection the fluid phase complement
activation was higher in the IVIG group than in the albumin group for C1rs/C1inh
complexes, C4bc, Bb and TCC. At the time of rejection both the albumin and the
IVIG group demonstrated interstitial tubular haemorrhage, vasculitis or necrosis
of glomerular capillaries and glomerular microthrombi. IgM, C1q, C3c, C4 and
fibrin were located in arteries and glomeruli and IgG in the interstitium in both
groups at rejection. The fluid phase findings are consistent with a modulatory
effect of IVIG on complement activation by deviating the classical pathway
activation towards the fluid phase. The prolonged survival of the IVIG-perfused
kidneys suggests that IVIG may be useful to dampen hyperacute rejection.
PMID- 9652826
TI - IgG subclasses in Lyme borreliosis: a study of specific IgG subclass distribution
in an interferon-gamma-predominated disease.
AB - Lyme borreliosis has shown a T helper type 1 (Th1)-like immune response with high
production of interferon-gamma. Since the cytokine environment seems to be
important in the regulation of immunoglobulin production and in the switch
between different isotypes and subclasses, and since the subclasses of IgG have
different functions, we wanted to examine the IgG subclass distribution in Lyme
borreliosis. We have developed an ELISA measuring flagellin-specific antibodies
of the different IgG subclasses in serum and cerebrospinal fluid (CSF). Thirty
five seropositive patients with varying manifestations of Lyme borreliosis were
included in the study. According to the results, the predominating subclasses in
both serum and CSF were IgG1 and IgG3. In samples taken early in disease this
pattern was more pronounced in patients with a subacute disease, defined as
recovery within 3 months, compared to patients that later on developed chronic
borreliosis. The levels of IgG2 were generally low and IgG4 was below detection
level. Thus, in the IFN-gamma-predominated immune response seen in Lyme
borreliosis, mainly IgG1 and IgG3 were found, i.e. the subclasses that are
complement activating as well as opsonizing in humans. Increased levels of these
two subclasses early in disease might contribute to recovery and counteract the
development of chronicity. The absence of IgG4 is in accordance with the presumed
Th1-like situation of Lyme borreliosis.
PMID- 9652827
TI - Interleukin-12 and perforin mRNA expression is augmented in blood mononuclear
cells in multiple sclerosis.
AB - Cytokines are suggested to orchestrate an abnormal immune response in multiple
sclerosis (MS). The regulatory cytokine interleukin (IL)-12 induces T-helper (Th)
cell switch to the Th1 type and the production by cytotoxic T cells of perforin,
a cell lysis-inducing factor. It has been suggested that Th1-like cytokines may
promote the development of MS, and the production of perforin to induce
oligodendrocyte damage. In-situ hybridization with radiolabelled synthetic
oligonucleotide probes was used to detect and enumerate mononuclear cells (MNC)
expressing IL-12 and perforin mRNA in blood and cerebrospinal fluid (CSF) from
patients with MS and controls. Plasma and CSF levels of IL-12 (p70) were
evaluated by ELISA. Higher numbers of IL-12 and perforin mRNA-expressing MNC were
registered in blood in MS and also in controls with aseptic meningoencephalitis
(AM) compared to healthy subjects. There were a few patients with other non
inflammatory neurological diseases who also had high levels of IL-12 or perforin
mRNA expressing blood MNC. A parallel elevation was observed for IL-12 (p70)
concentrations in plasma. In the MS patients' CSF, there was a further
augmentation of IL-12 mRNA expressing MNC. To evaluate autoantigen-induced IL-12
and perforin mRNA expression, blood MNC were cultivated +/- myelin basic protein
(MBP), a candidate autoantigen in MS. Higher numbers of MBP-reactive IL-12 and
perforin mRNA expressing blood MNC were detected in MS than controls. The
augmentation of both IL-12 and perforin in MS might reflect ongoing inflammatory
processes in MS and could represent targets for future treatments.
PMID- 9652828
TI - Increased levels of soluble tumour necrosis factor receptor-I (P55) and decreased
IgG1 reactivities in HIV-1 patients with cytomegalovirus disease.
AB - The purpose of the study was to investigate potential associations between tumour
necrosis factor (TNF), soluble TNF receptors (sTNF-Rs), immunoglobulin (Ig)G
subclasses and development of cytomegalovirus (CMV) disease amongst human
immunodeficiency virus (HIV)-1 patients. We enrolled HIV-1 patients with CD4
counts less than 100/microl in a prospective study and followed them over 1 year
for development of CMV disease. Concentrations of TNF, sTNF-RI, sTNF-RII and IgG
subclass reactivities were measured by ELISA; levels of CMV pp65 antigenaemia
were determined as numbers of pp65 expressing cells/100,000 cells and were
measured by staining of leucocytes; and HIV-1 RNA loads were measured by
polymerase chain reaction (PCR). Eighteen patients studied with CMV disease had
higher levels of sTNF-RI than 18 similar patients without CMV disease.
Concentrations of sTNF-RI correlated with levels of CMV antigenaemia in blood
samples collected before the development of CMV disease. Patients with CMV
disease had lower levels of IgG1 reactivities to CMV than patients without CMV
disease. We conclude that increased levels of sTNF-RI and decreased IgG1
reactivities are associated with an increased risk of development of CMV disease
among HIV-1 patients.
PMID- 9652829
TI - Allergen-induced synthesis of interleukin-5, but not of IgE, is a key mechanism
linked to symptomatic episodes of seasonal allergic rhinitis in sensitized
individuals.
AB - Some individuals with detectable levels of Japanese cedar (Criptomeria japonica)
pollen-specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms
during the pollen season. The response of CD4+ T-helper (Th) cells to the pollen
allergen might differ fundamentally between asymptomatic and symptomatic
individuals who are already sensitized to the pollen. The aim of this study was
to discern the possible differences in responses of peripheral blood mononuclear
cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic
subjects who have been sensitized to the pollen. This study included 20 non
atopic healthy volunteers (non-atopic group) and 48 patients who had detectable
levels of the pollen-specific IgE before the pollen season in 1997. In the review
of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms
of seasonal allergic rhinitis (symptomatic group), and the remainder had no
seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood
mononuclear cells (1.0 x 10(7) cells/well) were obtained from each individual
during the pollen season and cultured in the absence or presence of 12.5 microg
of Cry j 1 for 4 days. The concentrations of IgE, interleukin-5 (IL-5), and
interferon-gamma (IFN-gamma) in the culture supernatants were measured. The
levels of IgE produced by Cry j 1-stimulated PBMCs of the asymptomatic and
symptomatic groups were significantly higher than those of the non-atopic group,
but did not differ between the asymptomatic and symptomatic groups. The levels of
IL-5 produced by Cry j 1-stimulated PBMCs did not differ significantly between
the non-atopic group and the asymptomatic group, but the levels of IL-5 were
significantly higher in the symptomatic group than in the asymptomatic group as
well as the non-atopic group. The levels of IFN-gamma produced by Cry j 1
stimulated PBMCs did not differ significantly among the three groups. In
conclusion, our study has suggested that Japanese cedar pollen-induced synthesis
of IL-5, but not of IgE or IFN-gamma, is likely to be a key mechanism linked to
the symptomatic episode of seasonal allergic rhinitis in individuals sensitized
to the pollen.
PMID- 9652830
TI - Neutralization susceptibility of B subtype variant B" primary HIV-1 isolates. The
HEC/FIOCRUZ AIDS Clinical Research Group.
AB - Susceptibility to autologous and heterologous neutralization of primary human
immunodeficiency virus (HIV)-1 isolates belonging to subtype B, to the B"-variant
of subtype B or to subtype F from infected individuals residing in Rio de Janeiro
was assayed. A lower infectivity of the B"- and F isolates when compared to the
classical B-subtype HIV-1 isolates was observed. Comparisons of neutralization
susceptibilities were carried out for 19 B-subtype, 11 B"-variant and two F
subtype HIV-1 isolates with plasma from autologous and heterologous samples.
Frequency of autologous neutralization was slightly lower for B-subtype isolates
in comparison to B"-variant isolates. Heterologous intra-subtype neutralization
was significantly lower for B-subtype than for the B"-variant or the F-subtype
isolates. While B-subtype isolates were neutralized by most anti-F-subtype
plasma, F-subtype isolates, although most susceptible to F-subtype antibodies,
were highly susceptible to neutralization by anti-B-subtype antibodies. Cross
neutralization for B"-variant and B-subtype isolates was not as extensive as
observed for B- and F-subtype isolates. However, the results presented indicate a
quite extensive cross-neutralization between Brazilian HIV-1 isolates.
PMID- 9652831
TI - Placental transfer of IgG and IgG subclass antibodies anti-purified Escherichia
coli LPS O16, O6 and O111.
AB - We evaluated 22 paired maternal and cord sera regarding the presence of IgG and
IgG subclasses against purified Escherichia coli LPS O6, O16 and O111 employing
ELISA for titre and avidity analysis, isoelectric focusing associated with
affinity-blotting for spectrotypic analysis, and the Western-blotting technique
for recognition of the various bands in lipopolysaccharide (LPS). Levels of anti
LPS IgG antibodies in cord sera were equivalent to their respective maternal
sera, showing a significant correlation (P < 0.0001). IgG1 antibody levels were
higher in cord sera than in maternal sera (P < 0.005 for anti-O111, P < 0.05 for
anti-O16 and P < 0.02 for anti-O6). Cord IgG2 antibody levels were not different
from the maternal levels (P > 0.1). The levels of IgG3 and IgG4 were
undetectable. The avidity of anti-O6 and anti-O111 IgG in 10 cord sera showed an
extremely significant correlation with maternal antibody avidity (P < 0.0001).
Identical patterns of recognition were found in the paired samples analysed by
Western blotting. Most of the serum samples recognized the O-repetitive chains
and also the region corresponding to core and lipid A. Although the antibody
spectrotypes varied among individuals, paired cord and maternal serum samples
showed identical patterns. Our findings suggest the occurrence of placental
transfer of IgG antibodies against LPS O6, O16 and O111, mainly involving the
IgG1 or IgG2 subclasses.
PMID- 9652832
TI - Effect of combined transient androgen deprivation and irradiation following
radical prostatectomy for prostatic cancer.
AB - PURPOSE: To evaluate whether transient androgen deprivation improves outcome in
patients irradiated after radical prostatectomy for locally advanced disease,
persistent or rising postoperative prostate specific antigen (PSA), or local
recurrence. METHODS AND MATERIALS: Records of 105 consecutive patients who were
treated with pelvic irradiation after radical retropubic prostatectomy between
August 1985 and December 1995 were reviewed. Seventy-four patients received
radiation alone (mean follow up: 4.6 years), and 31 received transient androgen
blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor
blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up
3.0 years) for a mean duration of 6 months. Two of these patients were excluded
from further analysis because they received hormonal therapy for more than 1
year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction;
48 patients also received pelvic nodal irradiation to a median dose of 50 Gy.
Survival, freedom from clinical relapse (FFCR), and freedom from biochemical
relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was
defined as two consecutive PSA measurements exceeding 0.07 ng/ml. RESULTS: At 5
years after irradiation, actuarial survival for all patients was 92%, FFCR was
77%, and FFBR was 34%. FFBR was significantly better among patients who received
transient androgen blockade before and during radiotherapy than among those
treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also
superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014).
Potential clinical prognostic factors before irradiation did not differ
significantly between treatment groups, including tumor stage, summed Gleason
histologic score, lymph node status, indication for treatment, and PSA levels
before surgery or subsequent treatment. Multivariate analysis revealed that
transient androgen deprivation was the only significant predictor for biochemical
failure. CONCLUSION: This retrospective study of irradiation after radical
prostatectomy suggests that transient androgen blockade and irradiation may
improve freedom from early biochemical and clinically evident relapse compared to
radiotherapy alone, although more prolonged follow-up will be needed to assess
durability of impact upon clinical recurrence and survival rates.
PMID- 9652833
TI - Radiotherapy of bladder cancer: relevance of bladder volume changes in planning
boost treatment.
AB - PURPOSE: This study aims to evaluate tumor motion with controlled changes of the
bladder volume, and to assess the reproducibility of bladder (and tumor) position
using a urinary catheter balloon as an immobilization device. METHODS AND
MATERIALS: First, three patients with tumor growths in three different bladder
regions (trigone, left lateral wall, anterior wall) were evaluated. Three
dimensional CT-based reconstructed images were used to measure the displacement
of the tumors when 100 cc were removed from a bladder originally filled with 170
cc of contrast. The 3D calculated boost beam arrangements and field sizes for the
three tumors in the partially emptied bladders were used to simulate treatment of
the same tumors in the maximally filled bladders. Dose-volume histograms were
obtained. Second, verification of an ellipsoid model for bladder volume changes
was undertaken in 41 patients. Third, in eight additional patients a urinary
catheter balloon filled with 80-cc sterile saline solution was used in an attempt
to reproduce the shape and spatial coordinates of the bladder during the boost
treatment. A pair of orthogonal films with the 80-cc balloon filled with contrast
material were taken at simulation and repeated twice at weekly intervals during
radiotherapy. The reproducibility was quantified by sequentially calculating the
common surface of the bladder images in each orthogonal view. RESULTS: Target
motion, especially in the craniocaudal axis, appeared to be more relevant for
tumors arising in the bladder walls (15 mm) than in the trigone (5 mm).
Underdosage (<95% of the prescribed dose to the target volume) was observed in
20, 20, and 50% (with 1 cm margins around the tumor) and in 10, 10, and 15% (with
1.5 cm margins around the tumor) of the tumors arising in the trigone, left
lateral wall, and anterior wall, respectively. The ellipsoidal model was
validated with a strong correlation coefficient allowing to establish a
predictive model for bladder wall displacements as a function of bladder volume.
In the balloon reproducibility study, mean reproducibility factors of 0.84 (+/
0.06) and 0.82 (+/-0.07) were obtained for both anteroposterior and lateral
views, respectively. CONCLUSIONS: Changes in bladder volume and shape related to
bladder filling can result in clinically significant displacements of the target
volume. A minimum of 2-cm margins around the target may compensate for extreme
bladder volume changes during boost treatment. An ellipsoidal model for the
bladder is consistent with these observations. Although an 80-cc urinary catheter
balloon helped to immobilize the bladder, reproducibility was less than perfect.
PMID- 9652834
TI - Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers
during head and neck radiotherapy.
AB - PURPOSE: To evaluate the effectiveness of granulocyte macrophage-colony
stimulating factor GM-CSF mouthwashes in the epithelization of radiation-induced
oral mucosal ulceration, control of pain, and weight loss. METHODS AND MATERIALS:
Twelve patients received curative radiotherapy for head and neck carcinoma. All
had oropharyngeal and/or oral mucosa irradiation, with a median dose of 72 Gy
(range 50-74), with conventional fractionation. A total of 300 microg of GM-CSF
in 250 cc of water for 1 h of mouthwashing was prescribed. The procedure started
once oral ulceration in the irradiation field was detected. Patients, examined
twice a week, were evaluated for oral ulceration, pain, and weight loss. Blood
tests were taken weekly during GM-CSF administration. A comparison was carried
out with 12 retrospective case-matched controls. RESULTS: In the GM-CSF group,
mucosa ulcerations healed in 9 of 12 (75%) of the patients during the course of
the radiotherapy. Fifty percent of the patients said they felt less pain during
the GM-CSF treatment; 30% needed morphine. The mean and median weight loss as a
percentage of baseline weight in addition to the actual weight were 4.2% and 3%,
respectively (variation ranged between a gain of 1% and a loss of 13%). No GM-CSF
related side effects were found. In the case control group, in the 12 cases, oral
ulcerations increased during radiotherapy and two patients needed intubation
intake and hospital admission, as opposed to the GM-CSF group. The mean and
median percentage of weight loss were 5.8% and 5%, respectively. Sixty percent of
patients needed morphine, as opposed to 30% in the GM-CSF group. CONCLUSIONS:
Granulocyte macrophage-colony-stimulating factor was effective in curing mucosal
ulcerations during the course of radiotherapy. This is the first time we have
seen a drug with this capacity. Although the GM-CSF seems to be effective in the
control of pain, oral intake, and weight loss, we need further studies with a
greater number of patients to confirm our premise. Double-blind trials are
necessary for future research into the control of pain and weight loss.
PMID- 9652835
TI - Prognostic features and treatment outcome in locoregionally advanced
nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy.
AB - PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in
treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the
prognostic factors after CCRT have not been evaluated. We therefore attempt to
evaluate factors that influence treatment outcomes following CCRT. METHODS AND
MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with
locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered
either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per
day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5
fluorouracil. Cox proportional-hazards model was used to analyze the prognostic
factors which included age, gender, pathologic type, T, N, lactate dehydrogenase
(LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at
3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis
free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI:
65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow
up interval of 29 months (range 15-74 months). Cox proportional-hazards model
revealed that infiltration of the clivus and serum level of LDH before treatment
were the most two important factors that predict distant metastases. Infiltration
of the clivus and the serum LDH level greater than 410 U/L were strongly
associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002,
respectively). When these two risk factors were considered together, no distant
metastasis was observed in 40 patients with both intact clivus and LDH < or = 410
U/L. On the contrary, 13 of the remaining 34 patients with at least one risk
factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study
demonstrates that CCRT can improve the primary tumor control of 96.7% and disease
free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the
major cause of failure. Infiltration of the clivus by the tumor and LDH greater
than 410 U/L are the two independent and useful prognostic factors in patients
with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk
patients can be distinguished by virtue of their having both conditions.
PMID- 9652836
TI - Factors affecting mandibular complications in low dose rate brachytherapy for
oral tongue carcinoma with special reference to spacer.
AB - PURPOSE: To evaluate the efficacy of a spacer in the prevention of mandibular
complications in low dose rate (LDR) brachytherapy (BRT) for oral tongue
carcinoma. METHODS AND MATERIALS: A retrospective analysis was conducted using
103 patients with T1 or T2 tongue carcinoma treated by a single plane
implantation of iridium (192Ir) pins between 1979-1994. Of these patients, 60
were treated by BRT alone, and the rest were combined with external irradiation
(Ext) and/or chemotherapy (CHT). Forty-eight and 55 patients were given BRT with
and without a spacer, respectively. Spacers were individually made of acrylic
resin according to a prosthetic technique so as to obtain the thickness of 7-10
mm at the lingual part of the implanted side. Variables, including a spacer,
which may be associated with the development of osteoradionecrosis (ORN) of the
mandible, were analyzed by the Cox proportional hazards regression analysis.
RESULTS: Our spacer reduced about 50% of the absorbed dose at the lingual side
surface of the lower gingiva (LSG) to that in the absence of a spacer. Absolute
incidence of ORN was 2.1% (1 of 48) and 40.0% (22 of 55), with and without a
spacer, respectively, and the difference was statistically significant by
univariate analysis (p = 0.0004). It was revealed by the Cox analysis that the
spacer (p = 0.0247), combined CHT (p = 0.0295), and combined Ext (p = 0.0279)
were significant independent factors associated with the development of ORN. The
spacer was shown to be a significant factor by univariate analysis (p = 0.0037),
but not by multivariate analysis when analysis was restricted to the patients who
did not receive CHT. The absorbed dose, dose rate, and biological effective dose
(BED) reflecting early or late response were estimated at the LSG, and
prognosticators associated with the incidence of ORN were also determined by the
Cox analysis. Particularly, BED for late response by BRT, the total absorbed
dose, and any BED by Ext plus BRT were highly significant factors in the whole
population. Essentially similar results were obtained in the patients without
receiving CHT. CONCLUSIONS: It was clarified that our spacer effectively prevents
mandibular complications in LDR BRT by 192Ir for oral tongue carcinoma.
Furthermore, introduction of a spacer provided novel information concerning the
development of ORN, where BED particularly for late response given by BRT, the
total absorbed dose, and any BED by Ext plus BRT could be good prognostic factors
only when estimated at the LSG.
PMID- 9652837
TI - Conformal radiotherapy of Stage III non-small cell lung cancer: a class solution
involving non-coplanar intensity-modulated beams.
AB - PURPOSE: We developed a semiautomatic class solution to irradiate centrally
located Stage III non-small cell lung cancer (NSCLC), involving a beam intensity
modulation technique and optimization using a biophysical cost function. METHODS
AND MATERIALS: Treatment for 10 patients with Stage III NSCLC was planned, using
a conventional three- or four-beam three-dimensional (3D) technique and two
techniques involving, respectively, seven (BIM1) and five (BIM2) noncoplanar beam
incidences with intensity modulation. Two planning target volumes were defined:
PTV1 included macroscopic tumor volume and PTV2 included macroscopic and
microscopic disease. Beams were divided into beam parts (segments) and their
outlines were defined during virtual simulation. Optimization using a biophysical
cost function determined beam weights, segment weights, and wedge angles.
Biological end points included tumor control probability of both target volumes
(TCP1 and TCP2) and normal tissue complication probability (NTCP) of heart, lung,
and spinal cord. The resulting uncomplicated local control probability (UCLP) was
calculated. Physical end points included dose at PTV1 expressed as a dose minimum
and dose maximum. Target-dose inhomogeneity was constrained in all plans.
RESULTS: Concerning tumor evaluation, TCP1 was 74% (range 54-89%) for the 3D
plan, 78.0% (range 62-94%) for BIM1, and 86.0% (range 59-93%) for BIM2. TCP1*TCP2
was, respectively, 67.0% (range 39-81%), 73.0% (range 56-94%), and 81.0% (range
54-93%). Minimum doses to PTV1 were 85, 80, and 88 Gy with the three respective
techniques, while dose maxima were 89, 101, and 100 Gy. NTCPs of lung were 45.0%
(range 11-75%) for 3D, 19.5% (range 8-59%) for BIM1, and 24.5% (range 3-61%) for
BIM2. NTCPs of heart and spinal cord were comparable for all techniques. ULCPs
were 37.0% (range 9-73%), 52.5% (range 22-86%), and 60.0% (range 20-85%),
respectively. Applying physical limits to ensure clinical safety, minimum doses
at PTV1 were recalculated. These were 72, 71, and 74 Gy for 3D, BIM1, and BIM2,
respectively. CONCLUSION: The BIM2 plan is a candidate class solution for dose
escalation studies in centrally located Stage III NSCLC.
PMID- 9652838
TI - Results of treating primary tumors of the trachea with radiotherapy.
AB - PURPOSE: To report the efficacy of treatment and to identify prognostic factors
that were predictive of survival in primary tumors of the trachea treated with
radiotherapy. METHODS AND MATERIALS: The medical records of patients treated at
the Peter MacCallum Cancer Institute in the period 1962 to 1995 were reviewed.
Forty-two patients were eligible for the study and were treated with
radiotherapy. Squamous cell carcinoma (SCC) was the commonest subtype and
patients generally presented with long-standing respiratory symptoms. Eleven
patients were planned for treatment with at least 50 Gy to the primary, while the
rest were treated with lower doses. RESULTS: The estimated median survival for
all patients was 5.7 months, with 13% surviving at 2 years. Univariate analysis
revealed performance status, weight loss, and lymph node or distant metastatic
involvement as significant prognostic factors. Patients planned for treatment
with at least 50 Gy survived longer than patients treated with less than 50 Gy,
but this was probably due to selection of patients with better prognostic factors
for higher dose treatment.
PMID- 9652839
TI - Study of lung density corrections in a clinical trial (RTOG 88-08). Radiation
Therapy Oncology Group.
AB - PURPOSE: To investigate the effect of lung density corrections on the dose
delivered to lung cancer radiotherapy patients in a multi-institutional clinical
trial, and to determine whether commonly available density-correction algorithms
are sufficient to improve the accuracy and precision of dose calculation in the
clinical trials setting. METHODS AND MATERIALS: A benchmark problem was designed
(and a corresponding phantom fabricated) to test density-correction algorithms
under standard conditions for photon beams ranging from 60Co to 24 MV. Point
doses and isodose distributions submitted for a Phase III trial in regionally
advanced, unresectable non-small-cell lung cancer (Radiation Therapy Oncology
Group 88-08) were calculated with and without density correction. Tumor doses
were analyzed for 322 patients and 1236 separate fields. RESULTS: For the
benchmark problem studied here, the overall correction factor for a four-field
treatment varied significantly with energy, ranging from 1.14 (60Co) to 1.05 (24
MV) for measured doses, or 1.17 (60Co) to 1.05 (24 MV) for doses calculated by
conventional density-correction algorithms. For the patient data, overall
correction factors (calculated) ranged from 0.95 to 1.28, with a mean of 1.05 and
distributional standard deviation of 0.05. The largest corrections were for
lateral fields, with a mean correction factor of 1.11 and standard deviation of
0.08. CONCLUSIONS: Lung inhomogeneities can lead to significant variations in
delivered dose between patients treated in a clinical trial. Existing density
correction algorithms are accurate enough to significantly reduce these
variations.
PMID- 9652840
TI - Efficacy of total lymphoid irradiation for chronic allograft rejection following
bilateral lung transplantation.
AB - PURPOSE: To assess the safety and efficacy of total lymphoid irradiation (TLI) in
patients experiencing chronic rejection following bilateral lung transplantation
(BLT). PATIENTS AND MATERIALS: Eleven patients received TLI for chronic allograft
rejection (bronchiolitis obliterans syndrome) refractory to conventional
treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in
10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y
fields. Serial pre- and post-RT pulmonary function values, complete blood counts,
and immunosuppressive augmentation requirements [use of methylprednisolone,
murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal
antithymocyte globulin (ATG), and tacrolimus] were monitored. RESULTS: In the 3
months preceding TLI, the average decrease in forced expiratory volume in 1 s
(FEV1) was 34% (range 0-75%) and the median number of immunosuppression
augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI
treatment fractions. Reasons for discontinuation included progressive pulmonary
decline (four patients), worsening pulmonary infection (two patients), and
persistent thrombocytopenia (one patient). Seven of the 11 patients failed within
8 weeks of treatment cessation. One patient had unabated rejection and received
bilateral living related-donor transplants; he is alive and well. Six patients
died. Two of these deaths were due to pulmonary infection from organisms isolated
prior to the start of RT; the other four deaths were from progressive pulmonary
decline. The four remaining patients had durable positive responses to TLI (mean
follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3
months following treatment, these four patients had improvements in average FEV1
(40% decline vs. 1% improvement) and fewer median number of immunosuppressive
augmentations (3.5 vs. 0). None of these patients has developed
lymphoproliferative disease or has died. Features suggestive of a positive
response to TLI included longer interval from transplant to RT, higher FEV1 at
initiation of RT, and absence of preexisting pulmonary infection. CONCLUSION:
Total lymphoid irradiation for chronic allograft rejection refractory to
conventional medical management following BLT was tolerable. A subset of patients
experienced durable preservation of pulmonary function and decreased
immunosuppressive requirements. Patients with rapidly progressive allograft
rejection, low FEV1, or preexisting infection were least likely to benefit from
irradiation. Early initiation of TLI for patients experiencing chronic allograft
rejection following BLT may be warranted.
PMID- 9652841
TI - Local and distant recurrence after conservative management of "very low-risk"
breast cancer are dependent events: a 10-year follow-up.
AB - PURPOSE: To determine the risk factors associated with recurrence after breast
conserving treatments, and the relationship between occurrence of a local
recurrence and subsequent distant metastases. METHODS AND MATERIALS: Among the
3697 patients with primary breast cancer treated at Institut Paoli-Calmettes
Cancer Center, Marseille, between 1980 and 1995, we retrospectively analyzed 756
patients who had been treated with conservative surgery with uninvolved margins
of excision, were node-negative, and had received uniform radiotherapy and no
chemotherapy. One third of the patients received hormonal therapy via tamoxifen
or surgical castration. The endpoints considered were local failures and distant
metastases. All tumors were reviewed by our pathologists. The median follow-up
for the 700 survivors was 62 months. RESULTS: In the multivariate analysis,
histological multifocality (p = 0.0076), peritumoral vessel invasion (p =
0.0215), and young age (p = 0.0245) were associated with an increased risk of
local recurrences, whereas tumor size (p = 0.0013), young age (p = 0.003), and
histological multifocality (p = 0.0414) were associated with an increased risk of
distant metastases. Local recurrences and distant metastases had similar yearly
event probabilities. Median time to distant metastases was shorter after a local
recurrence. Early timing of local recurrences did not mark a higher risk of
distant metastases. Hazard of relapsing from distant metastases was 4.4 times
higher after a local recurrence. CONCLUSION: our results support the hypothesis
that, in this subset of patients, local recurrences favor further dissemination
of cancer cells. We are unable to clearly identify a group who would benefit from
more aggressive local therapy.
PMID- 9652842
TI - Thallium-201 perfusion scintigraphy in the evaluation of late myocardial damage
in left-side breast cancer treated with adjuvant radiotherapy.
AB - PURPOSE: To evaluate late myocardial damage after adjuvant radiotherapy using a
mixed-beam (photons plus electrons) technique to treat the internal mammary lymph
nodes in left-side breast cancer. METHODS AND MATERIALS: A bicycle ergometer
stress test coupled with thallium-201 perfusion scintigraphy and analysis by
single-photon computed tomography (CT) was performed on 19 patients treated with
left-side breast/chest wall and internal mammary radiation for breast cancer
between 1987 and 1993. To be sure that we would evaluate late toxicity caused by
the irradiation, patients had to fulfill the following eligibility criteria: left
side breast cancer, treatment between 1987 and 1993 and no recurrence during
follow-up, age < or = 75 years, no known risk for coronary artery disease, no
previous chemotherapy, internal mammary field treated with an association of
photons and electrons, and CT scan-based treatment planning. RESULTS: Median age
at scintigraphy was 59 years. Two patients did not reach optimal exercise level
and were not evaluable. Among the 17 evaluable patients representing 91.6 patient
years of follow-up, there were no perfusion defects by visual or quantitative
analysis. CONCLUSION: The mixed-beam technique seemed to spare the heart from
harmful irradiation and to protect the myocardium. Results need to be confirmed
on the long-term use of this technique.
PMID- 9652843
TI - Twice-daily fractionation of external irradiation with brachytherapy and
chemotherapy in carcinoma of the cervix with positive para-aortic lymph nodes:
Phase II study of the Radiation Therapy Oncology Group 92-10.
AB - PURPOSE: The purpose of this study was to evaluate the toxicity and efficacy of
twice-daily external irradiation to the pelvis and para-aortics with
brachytherapy and concurrent chemotherapy for carcinoma of the cervix with
positive para-aortic lymph nodes. METHODS AND MATERIALS: This study was designed
to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para
aortics at 4- to 6-h intervals, 5 days per week. The total external radiation
doses were 24 to 48 Gy to the whole pelvis, 12 to 36 Gy parametrial boost, and 48
Gy to the para-aortics with an additional boost to a total dose of 54 to 58 Gy to
the known metastatic para-aortic site. One or two intracavitary applications were
performed to deliver a total minimum dose of 85 Gy to point A. Cisplatin (75
mg/m2, days 1 and 22) and 5-FU (1000 mg/m2/24 h x 4 days; days 1 and 22) were
given for two or three cycles. RESULTS: Twenty-nine patients with clinical Stages
I to IV carcinoma of the cervix with biopsy-proven para-aortic lymph nodes were
enrolled in this study. Hyperfractionated external radiotherapy was completed in
86% (25 of 29). Brachytherapy was given in two applications to 48% (14 of 29),
31% (9 of 29) had one intracavitary application, 14% (4 of 29) had no
brachytherapy, one had three applications, and one had five HDR applications.
Radiotherapy was completed per protocol in 69%. Three courses of chemotherapy
were given to 24% (7 of 29), 72% (21 of 29) received two courses, and one patient
did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in
3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Radiotherapy toxicity was
Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5
toxicity occurred and the patient died from a myocardial infarction from
chemotherapy and radiotherapy colitis during her course of therapy. The median
follow-up time was 18.9 months. The overall survival estimates were 59% at 1 year
and 47% at 2 years. The probability of local-regional failure was 38% at 1 year
and 49% at 2 years. The probability of disease failure at any site was 45% at 1
year and 59% at 2 years. CONCLUSION: The results suggest that twice-daily
external irradiation to the pelvis and para-aortics with brachytherapy and
concurrent chemotherapy resulted in an unacceptably high rate (31%, 9 of 29) of
Grade 4 nonhematologic toxicity. One patient died from complications of therapy.
Radiotherapy was completed per protocol in 69%. The survival estimates appear no
better than standard fractionation radiotherapy without chemotherapy. Additional
follow-up is necessary for long-term survival estimates.
PMID- 9652844
TI - The prognostic significance of pre- and posttreatment SCC levels in patients with
squamous cell carcinoma of the cervix treated by radiotherapy.
AB - PURPOSE: To investigate the prognostic significance of the pre- and posttreatment
serum squamous cell carcinoma antigen (SCC) levels in patients with Stage I-IVA
squamous cell carcinoma of the cervix primarily treated by radiotherapy.
MATERIALS AND METHODS: 401 patients with squamous cell carcinoma of cervix
primarily treated with radiotherapy (RT) were included in this study. All had
preRT, and 249 patients had postRT serum SCC values. The association of
pretreatment SCC level with the clinical parameters, including stage, hemoglobin
(Hb) level, age, cell differentiation, and lymph node status, was assessed by
univariate and multivariate analysis. The prognostic significance of pretreatment
SCC level and these clinical parameters were evaluated. The impact of postRT
residual induration and SCC levels on survival was analyzed. RESULTS: 1. PreRT
SCC level strongly correlated with stage. After controlling for stage, only SCC
levels higher than 10 ng/ml were associated with enlarged lymph nodes shown in CT
scan. No association of preRT SCC level with other clinical parameters was found.
2. SCC level higher than 10 ng/ml, but not between 2-10 ng/ml, had significant
impact on survival in a multivariate analysis. Stage, Hb levels (<10 g/dl) and
positive lymph node shown by CT scan were also independent prognostic factors for
survival. No significant difference in failure pattern in terms of local and/or
distant sites was found in patients with different SCC levels. 3. Patients with
residual induration and/or persistently elevated SCC level at 2-3 months after RT
had a significantly higher incidence of treatment failure. Persistently elevated
SCC level is a stronger predictor for treatment failure than residual induration
by pelvic examination, and is associated with a higher incidence of distant
metastasis. One third of patients with initial SCC level higher than 10 ng/ml had
persistently elevated SCC. CONCLUSION: Pretreatment SCC levels higher than 10
ng/ml are an independent predictor for poor prognosis in patients included in
this study, and can be used as one of the prognostic factors for selection of
patients for intensive treatment. Persistently elevated SCC levels after RT is a
strong predictor for treatment failure. A combination of clinical pelvic
examination and SCC levels provides useful information for the need of further
work-up and management.
PMID- 9652845
TI - Interstitial radiation for recurrent cervix or endometrial cancer in the
suburethral region.
AB - Recurrent tumors in the suburethral area are uncommon, but potentially morbid
lesions. Brachytherapy, with or without external beam irradiation, was used to
treat 10 consecutive women with lesions ranging from 1-6 cm in the suburethral
area. All women achieved local control, with one woman developing a serious
complication. Four of the 10 women remain alive without evidence of disease. A
high rate of distant metastasis in those women who have recurred despite previous
adjuvant pelvic radiation following hysterectomy for endometrial cancer should
prompt the investigation of effective systemic chemotherapeutic agents.
PMID- 9652846
TI - Sensory and motor dysfunction assessed by anorectal manometry in uterine cervical
carcinoma patients with radiation-induced late rectal complication.
AB - PURPOSE: To investigate the effects of radiation on anorectal function in
patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Anorectal
manometry was carried out on 24 patients (complication group) with late radiation
proctitis. All of the manometric data from these patients were compared with
those from 24 age-matched female volunteers (control group), in whom radiation
treatment had not yet been performed. RESULTS: Regardless of the severity of
proctitis symptoms, 25% of patients demonstrated all their manometric data within
the normal range, but 75% of patients exhibited one or more abnormal manometric
parameters for sensory or motor functions. Six patients (25%) had an isolated
sensory dysfunction, eight patients (33.3%) had an isolated motor dysfunction,
and four patients (16.7%) had combined disturbances of both sensory and motor
functions. The maximum tolerable volume, the minimal threshold volume, and the
urgent volume in the complication group were significantly reduced compared with
those in the control group. The mean squeeze pressure in the complication group
was significantly reduced, whereas the mean resting pressure and anal sphincter
length were unchanged. CONCLUSIONS: Physiologic changes of the anorectum in
patients with late radiation proctitis seem to be caused by a variety of sensory
and/or motor dysfunctions in which many different mechanisms are working
together. The reduced rectal reservoir capacity and impaired sensory functions
were crucial factors for functional disorder in such patients. In addition,
radiation damage to the external anal sphincter muscle was considered to be an
important cause of motor dysfunction.
PMID- 9652847
TI - Effect of filgrastim (G-CSF) during chemotherapy and abdomino-pelvic radiation
therapy in patients with ovarian carcinoma.
AB - PURPOSE: To evaluate the safety and effectiveness of filgrastim (granulocyte
colony-stimulating factor, G-CSF) in reducing neutropenia and treatment
interruptions during whole abdominal radiotherapy for ovarian cancer. METHODS AND
MATERIALS: Sixteen patients with ovarian cancer treated with 2 to 6 courses of
cisplatin-containing chemotherapy and abdomino-pelvic radiation therapy received
filgrastim for neutrophil counts <2 x 10(9)/L. Endpoints for analysis included
the ability to maintain the neutrophil count in the target range, number of
treatment interruptions due to neutropenia, and toxicity attributed to
filgrastim. RESULTS: Fourteen patients received a mean of 2.9 courses of
filgrastim (each with a mean duration of 4.1 days), with no treatment
interruptions due to neutropenia. The majority of neutrophil counts were
maintained above the target range of 2 x 10(9)/L during treatment.
Thrombocytopenia requiring treatment interruption was seen in six patients and
necessitated platelet transfusions in one. Thrombocytopenia occurred at a mean
abdominal radiation dose of 2207 cGy and in all but one patient was preceded by
one or more episodes of neutropenia. In comparison with a control group of 31
patients treated without filgrastim there was no reduction in treatment
interruptions. Four patients did not complete treatment because of persistent
thrombocytopenia yet received a mean of 94% of the planned abdominal radiation
dose and 69% of the planned pelvic dose. Filgrastim toxicity was limited to mild
skeletal pains in six patients and a Grade 1 skin rash in two patients.
CONCLUSIONS: Filgrastim is safe and effective in preventing neutropenia and
reducing neutropenic treatment interruptions during abdominal radiotherapy in
patients with ovarian cancer. However, there was no clear benefit to the use of
filgrastim as thrombocytopenia became the dose-limiting toxicity resulting in a
risk of treatment interruptions and early termination of radiotherapy.
PMID- 9652848
TI - Clinical results of 24 pituitary macroadenomas with linac-based stereotactic
radiosurgery.
AB - PURPOSE: To determine the impact of stereotactic radiosurgery (SRS) on the
clinical course, hormonal status, and follow-up CT/MRI scan of pituitary
macroadenomas. METHODS AND MATERIALS: From July 1988 to March 1996, 24 pituitary
macroadenomas had been treated using 6 MV linear accelerator based SRS. They
consisted of 11 (45.8%) prolactinomas, 2 (8.3%) growth hormone (GH)-secreting
tumors, 1 (4.2%) Cushing's disease, 8 (33.3%) nonsecreting (nonfunctioning: NF)
tumors, and 2 (8.3%) mixed prolactin-growth hormone (PRL-GH)-secreting tumors
(M:F = 12:12; aged 21-61 years). Postoperative irradiation was performed in all
cases except for the instance of Cushing's disease. The prescribed dose to tumor
center varied from 10 to 27 Gy (mean 21.1 Gy) using a collimator size of 0.5 to
2.5 cm. The follow-up duration ranged from 13 to 89 months (mean 49.2 months).
Results from these patients were compared to our results using conventional
radiation. RESULTS: Visual acuity and field defect were improved or became normal
in 19 (79.2%) cases. Four (16.7%) remained unchanged after the treatment. One
(4.1%) progressed 6 years after SRS and subsequently had repeat surgery with
conventional boost irradiation. Of the 13 (46.4%) prolactinomas, including two
mixed PRL-GH secreting tumors, 11 (84.1%) revealed normal hormonal levels within
1 year after SRS. In contrast, it took 2 years to become normal after
conventional radiation therapy. In four GH-secreting tumors including two mixed
PRL-GH secreting tumors, SRS and conventional methods showed similar responses.
On follow-up imagings of the 21 patients, the mass was completely resolved in 4
(16.7%), including 3 PRLs and one NF, decreased in 11 (45.8%), and unchanged in 5
(16.7%) with central necrosis or cysts. One (4.2%) progressed and was reoperated
6 years after treatment. The complications related to SRS were comparable to
those from conventional method. CONCLUSION: Radiosurgery can be used effectively
in patients with pituitary adenoma. In this study, a more rapid hormonal and
clinical response was achieved with radiosurgery than with conventional pituitary
irradiation treatment.
PMID- 9652849
TI - Single-fraction stereotactic radiotherapy: a dose-response analysis of
arteriovenous malformation obliteration.
AB - PURPOSE: Stereotactic radiotherapy delivered in a high-dose single fraction is an
effective technique to obliterate intracranial arteriovenous malformations (AVM).
To attempt to analyze the relationships between dose, volume, and obliteration
rates, we studied a group of patients treated using single-isocenter treatment
plans. METHODS AND MATERIALS: From May 1986 to December 1989, 100 consecutive
patients with angiographically proven AVM had stereotactic radiotherapy delivered
as a high-dose single fraction using a single-isocenter technique. Distribution
according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0
grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in
11, and large and irregular in 15. The targeted volume of the nidus was estimated
using two-dimensional stereotactic angiographic data and, calculated as an ovoid
shaped lesion, was 1900 +/- 230 mm3 (median 968 mm3; range 62-11, 250 mm3). The
mean minimum target dose (Dmin) was 19 +/- 0.6 Gy (median 20 Gy; range: 3-31.5).
The mean volume within the isodose which corresponded to the minimum target dose
was 2500 +/- 300 mm3 (median 1200 mm3; range 75-14 900 mm3). The mean maximum
dose (Dmax) was 34.5 +/- 0.5 Gy (median 35 Gy; range 15-45). The mean
angiographic follow-up was 42 +/- 2.3 months (median 37.5; range 7-117). RESULTS:
The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate
was 62.5 +/- 7%. After univariate analysis, AVM obliteration was influenced by
previous surgery (p = 0.0007), Dmin by steps of 5 Gy (p = 0.005), targeted volume
of the nidus (< or = 968 mm3 vs. >968 mm3; p = 0.015), and grade according to
Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate
analysis, the independent factors influencing AVM obliteration were the Dmin
[relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and
grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p =
0.010). Delayed complications were observed in eight patients. The 5-year
actuarial rate of delayed complications was 7.4%. CONCLUSION: After stereotactic
radiotherapy delivered in a single high dose using a single-isocenter technique,
the success rate for complete obliteration is independently correlated to Dmin
but does not seem to be influenced by Dmax and the targeted volume of the nidus.
PMID- 9652850
TI - Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid
carcinoma of the anal canal.
AB - PURPOSE: To evaluate the efficacy of induction chemotherapy in combination with
radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma.
METHODS AND MATERIALS: Thirty-one patients diagnosed during the period 1989-1994
with loco-regionally advanced cancer of the anal canal (phiTmax > or = 4 cm or T4
or N+) were treated with induction chemotherapy consisting of one to three
courses of carboplatin (300-375 mg/m2 i.v.) and 5-fluorouracil [5,000 mg/(m2 x
120 h) i.v.] followed by external beam irradiation +/- surgery. RESULTS: The
toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after
the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor
specific survival, freedom from recurrence, preservation of sphincter, and event
free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%,
respectively. CONCLUSION: The results are promising but a well-designed
randomized trial is needed to further elucidate the role of induction
chemotherapy in the treatment of loco-regionally advanced anal carcinoma.
PMID- 9652851
TI - In vitro radiosensitization of human cervical carcinoma cells by combined use of
13-cis-retinoic acid and interferon-alpha2a.
AB - BACKGROUND: Significant antitumor activity has been reported with the combined
use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFN-alpha) in the
treatment of advanced-stage cervical cancers and skin cancers. Since IFN-alpha
has been shown to be a modest radiation enhancer for selected malignant tumor
cells and the cytotoxic activity is more enhanced by combining cRA and IFN-alpha,
we hypothesized that the exposure of selected human carcinoma cells to combined
cRA and IFN-alpha would render the cells highly radiosensitive. METHODS AND
MATERIALS: Two human cervical carcinoma cell lines, ME-180 and HeLa-S3, were
chosen for the present study because of the different characteristics of the
retinoic acid receptor status of the cell lines. To demonstrate the effects of
combined cRA and IFN-alpha treatment on radiation response, we exposed the cells
to cRA, IFN-alpha, or a combination of the drugs for 72 h before radiation.
Experiments were carried out at minimally cytotoxic concentrations of the drug
for radiation studies. End points of the study were cell growth inhibition and
clonogenic ability of the single-plated cells. Effects of cRA and IFN-alpha on
radiation response were quantitatively analyzed by constructing the radiation
cell survival curves of ME-180 and HeLa cells. RESULTS: ME-180 cells exhibited
varying degrees of cytotoxicity with cRA and IFN-alpha, while HeLa cells showed
no toxic effects with the same treatment. Combined treatment of cRA and IFN-alpha
produced an additive cytotoxic effect in ME-180 cells. Radiosensitization was
minimal when ME-180 cells were treated with either cRA or IFN-alpha before
radiation. When ME-180 cells were exposed to 10 microM cRA for 48 h and 1000 U/ml
IFN-alpha for 24 h prior to radiation, there was a significant enhancement in
radiation-induced cell killing; the dose modification factor was 2.1 +/- 0.9 at
the 1% cell-survival level. On the other hand, HeLa-S3 cells exhibited no
increased cytotoxicity or radiation enhancement under the same experimental
conditions. CONCLUSION: The present data provide a radiobiological basis for
using cRA and IFN-alpha as a combination radiosensitizer in selected human
carcinoma cells.
PMID- 9652852
TI - Radiosensitizing potential of gemcitabine (2',2'-difluoro-2'-deoxycytidine)
within the cell cycle in vitro.
AB - PURPOSE: Gemcitabine (2',2'-difluorodeoxycytidine; dFdCyd) is a new deoxycitidine
analog which exhibits substantial activity against solid tumors and
radiosensitizing properties in vitro. To examine cell cycle-specific effects of a
combined treatment with gemcitabine and radiation, the in vitro clonogenic
survival of two different cell lines was measured for cells from log-phase
culture, G1 and S-phase cells. METHODS AND MATERIALS: Chinese hamster (V79) and
human colon carcinoma (Widr) cells were exposed to different radiation doses and
for different points of time relative to gemcitabine treatment (2 h). Experiments
were also carried out with different cell-cycle populations obtained after
mitotic selection (V79) or after serum stimulation of plateau-phase cells (Widr).
The resulting survival curves were analyzed according to the LQ model, and mean
inactivation doses (MID) and the cell cycle-specific enhancement ratios (ER) were
calculated from the survival curve parameters. RESULTS: Effectiveness of combined
treatment of log-phase cells was greatest when cells were irradiated at the end
of the gemcitabine exposure [ER: 1.28 (V79), 1.24 (Widr)]. For later times after
the removal of the drug, radiosensitization declined, approaching independent
toxicity. From the time course of interactive-type damage decay half-life values
of 75 min (V79) and 92 min (Widr) were derived. Gemcitabine did not
radiosensitize G1 Widr cells or V79 cells from the G1/S border, but substantial
radiosensitization was observed for the S-phase cell preparations [ER: 1.45 (V79
lateS), 1.57 (Widr)]. CONCLUSIONS: Treatment of cells with gemcitabine
immediately before irradiation eliminates, or at least greatly reduces, the
variation in radiosensitivity during the cell cycle that is manifested by
radioresistance during S phase. This reversal of S-phase radioresistance could
imply that gemcitabine interferes with the potentially lethal damage
repair/fixation pathway. Other approaches have been taken to overcome S-phase
radioresistance, such as hyperthermia or densely ionizing radiation, and combined
treatments with dFdCyd could prove of value to complement such efforts.
PMID- 9652853
TI - Selective in vivo radiosensitization by 5-fluorocytosine of human colorectal
carcinoma cells transduced with the E. coli cytosine deaminase (CD) gene.
AB - PURPOSE: The E. coli cytosine deaminase (CD) gene encodes an enzyme capable of
converting the nontoxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU),
a known radiosensitizer. Having previously shown that combined CD suicide gene
therapy and radiation (RT) results in pronounced radiosensitization in vitro, we
progressed to in vivo studies of combined therapy. METHODS AND MATERIALS: WiDr
human colon cancer cells were transduced in vitro with the CD gene and cells
expressing CD were selected for use as xenografts in a nude mouse model. After
administration of 5-FC, tumors received 10-30 Gy local field radiation (RT) and
tumor growth delay was compared to control animals receiving either 5-FU, 5-FC,
or RT alone. RESULTS: Maximal growth delay was seen in mice treated with 5-FC for
6 consecutive days prior to RT. Combined treatment with 15 Gy radiation resulted
in a dose-modifying factor (DMF) of 1.50, and a greater DMF was observed with
higher doses of radiation. There was no appreciable toxicity using this new
approach. In contrast, a similar treatment of combined 5-FU and radiation
resulted in considerable toxicity and no appreciable radiosensitization.
CONCLUSION: The present results show that combined suicide gene therapy and RT
results in pronounced antitumor effect without any notable toxicity. This
indicates that the CD gene may be useful in the development of novel treatment
strategies combining radiation and gene therapy in the treatment of locally
advanced cancers.
PMID- 9652854
TI - Murine strain differences in the volume effect and incidence of radiation-induced
colorectal obstruction.
AB - PURPOSE: Interindividual variation in the level of normal tissue damage after
radiotherapy has been clinically observed. Murine models have suggested that
there may be a genetic component to the variation in susceptibility of different
radiation-induced normal tissue complications. Currently, there are no
experimental data available describing interstrain differences in the "volume
effect" for irradiated normal tissues, such as the colorectum. The aims of this
study are to determine if there are strain differences in: 1. the incidence of
colorectal obstruction; and 2. the volume effect, after irradiation of the
colorectum using two mouse strains that are known to vary in their susceptibility
for developing pulmonary fibrosis. METHODS AND MATERIALS: Various lengths (5.2 to
22.9 mm) of the colorectum of male C57B1/6 and C3Hf/Kam mice were irradiated with
a single dose (30 Gy) of 137Cs gamma rays. Also, various doses (20 to 35 Gy) were
given to a single length (22.9 mm) of colorectum. The incidence of obstruction
was determined as a function of length and dose at 6 months after irradiation.
The Threshold Probability model was fit to the length-response data. RESULTS:
C57B1/6 mice developed colorectal obstruction at significantly higher incidence
than C3Hf/Kam mice at all lengths after a single dose of 30 Gy. In addition, the
data showed a strain difference in the threshold length of colorectum that had to
be irradiated before obstructions were observed. CONCLUSION: Strain differences
in the incidence of radiation-induced colorectal obstruction were observed,
consistent with previous studies that showed a strain difference in radiation
induced pulmonary fibrosis. The presence of a threshold length of colorectum that
was different for the two strains is consistent with the concept that there may
be a critical threshold amount of colorectal tissue that can tolerate a high dose
without complication, and that the dimensions of the threshold may vary among
individuals.
PMID- 9652855
TI - Increased induction of Ca2+-mediated differentiation by gamma ray is mediated by
endogenous activation of the protein kinase C signaling pathways in mouse
epidermal cells.
AB - PURPOSE: The aim of this study was to determine whether gamma-rays can affect
Ca2+-induced differentiation in normal and neoplastic mouse epidermal cells.
METHODS AND MATERIALS: After gamma-ray irradiation, primary and v-rasHa
transformed mouse keratinocytes were cultured for 48 h in 0.12 mM Ca2+-containing
media, and cellular translocation from cytosolic to particulated fraction of each
PKC isozyme and expressions of differentiation markers were examined. RESULTS:
Morphological difference was seen at 48 h after irradiation in both Ca2+-shifted
normal and v-rasHa transformed cells; v-rasHa cells were more resistant to the
radiation than normal cells. Radiation potentiated granular cell-differentiation
marker expressions (filaggrin, loricrin, and SPR-1) in both normal and v-rasHa
transformed cells. In the case of spinous cell markers, the expression of
keratins K1 and K10, which are usually blocked in v-rasHa cells was increased
after irradiation. However, there was no change of K8 expression level, which can
be seen only after v-rasHa transfection. Cellular fractionation and immunoblot
analysis with antibodies against PKCalpha, delta, epsilon, eta, and xi revealed
that PKCalpha was responsible for the differentiation marker expression.
CONCLUSIONS: These findings suggest that PKCalpha is an important component of
the signaling pathway regulating radiation-induced differentiation in both normal
and neoplastic epidermal cells.
PMID- 9652856
TI - Effects of radiation on endothelial function.
AB - PURPOSE: The response of endothelium to ionizing radiation was studied. METHODS
AND MATERIALS: The abdominal aorta in different experimental groups of rats was
irradiated, and the response of arterial rings from the irradiated segments to
norepinephrine, acetylcholine (ACh), and nitroglycerin (NTG) was studied.
Nonirradiated thoracic segments in the same experimental animals were used as as
a control for comparisons. Two age-matched nonirradiated control groups were also
studied. RESULTS: A poor endothelium-dependent vasodilator response was obtained
with ACh in the irradiated rings and also in those not directly irradiated; the
endothelium-independent vasodilator response to NTG was preserved during the
first 3 days after irradiation. By 6 months, both the endothelium-dependent
response and endothelium-independent response were impaired. CONCLUSIONS:
Alterations in nitric oxide synthesis and/or release by the endothelium were
observed during the early phase of radiation in irradiated and nonirradiated
segments. In the delayed phase of radiation, endothelium-independent muscular
relaxation was also affected.
PMID- 9652857
TI - Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells.
AB - PURPOSE: The kinetics of the accumulation of inducible 72-kD heat shock protein
(hsp72) and the activation of heat shock transcriptional factor (HSF) after
hyperthermia and/or CDDP treatment in two human glioblastoma cell lines, A-172
having the wild-type p53 gene and T98G having the mutated p53 gene were
evaluated. METHODS AND MATERIALS: Western blot analysis of hsp72, gel-mobility
shift assay of HSF, cell survival, and development of thermotolerance were
examined. RESULTS: The prominent suppression of heat-induced hsp72 accumulation
by CDDP was seen in A-172 cells, but not in T98G cells. This was due to the p53
dependent inhibition of heat-induced HSF activation by CDDP. The interactive
hyperthermic enhancement of CDDP cytotoxicity was observed in A-172 cells, but
not in T98G cells. In addition, the heat-induced thermotolerance was suppressed
by the presence of CDDP in the pretreatment. CONCLUSION: Suppression of heat
induced hsp72 accumulation by CDDP contributes to an interactive hyperthermic
enhancement of CDDP cytotoxicity in the cells bearing the wild-type p53 gene.
PMID- 9652858
TI - Centralized multiinstitutional postimplant analysis for interstitial prostate
brachytherapy.
AB - PURPOSE: To investigate the feasibility and utility of performing centralized
postimplant analysis for transperineal interstitial permanent prostate
brachytherapy (TIPPB) by conducting a pilot study that compares the results
obtained from 125I implants conducted at five different institutions. METHODS AND
MATERIALS: Dose-volume histogram (DVH) analysis was performed on 10 postimplant
CT scans from each of five institutions. This analysis included the total
implanted activity of 125I, ultrasound, and CT volumes of the prostate, target
volume ratios, dose homogeneity quantifiers, prostate dose coverage indices, and
rectal doses. As a result of the uncertainty associated with the delineation of
the prostatic boundaries on a CT scan, the contours were redrawn by a single,
study center physician, and a repeat DVH analysis was performed. This provided
the basis for comparison between institutions in terms of implant technique and
quality. RESULTS: By comparing total activity to preimplant ultrasound volume we
clearly demonstrated that differences exist in implant technique among these five
institutions. The difficulty associated with determining glandular boundaries on
CT scans was apparent, based upon the variability in prostate volumes drawn by
the various investigators compared to those drawn by the study center physician.
This made no difference, of course, in the TVR or homogeneity quantifiers that
are independent of target location. Furthermore, this variability made
surprisingly little difference in terms of dose coverage of the prostate gland.
Rectal doses varied between institutions according to the various implant
techniques. CONCLUSIONS: Centralized, outcome-based evaluation of transperineal
interstitial permanent prostate brachytherapy is viable and appropriate. Such an
approach could be reasonably used in the conduct of multiinstitutional trials
used to study the efficacy of the procedure.
PMID- 9652859
TI - Clinical variability of target volume description in conformal radiotherapy
planning.
AB - PURPOSE: The pivotal step in radiation planning is delineation of the target
volume and production of a treatment plan to encompass this. This study assesses
the variation of physicians in creation of these volumes. METHODS AND MATERIALS:
Three radiologists and eight radiation oncologists outlined the gross tumour
volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In
addition, the radiation oncologists (RO) created a planning target volume
according to a set protocol for all cases. Volumes were produced and comparison
of these volumes and the position of the isocenters were analysed. In addition,
the margins allowed were measured and compared. RESULTS: There was a maximum
variation ratio (largest to smallest volume outlined) of the GTV in the four
cases of 1.74 among radiologists and 3.74 among oncologists. There was a
significant difference (p = 0.01) in mean GTV between RO and the radiologists.
The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean
difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from
1.25 to 3.33. There was no significant difference in mean PTV values between the
two groups of ROs divided by specialization in uro-oncology. The mean variation
in location of the isocenter from the centroid of the radiologists' volume in the
four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values
from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm.
Minimum margins allowed in each case varied from minus 7 mm to 9 mm. CONCLUSION:
This study demonstrates significant interphysician variability in producing
target volumes and radiation plans for conformal radiotherapy. The scale of this
difference is clearly of significance, with up to 3-fold variation in volumes
delineated by clinicians. The factors leading to these differences will be
further addressed. The existence of such variability, however, clearly needs to
be accepted as a factor in the overall uncertainty analysis in conformal
radiotherapy planning.
PMID- 9652860
TI - A commercial IMRT treatment-planning dose-calculation algorithm.
AB - PURPOSE: The dose-calculation algorithm for a commercial arc-based intensity
modulated radiation therapy (IMRT) treatment-planning and delivery system
(Peacock, NOMOS Corporation) is described. METHODS AND MATERIALS: The IMRT
delivery system uses a dynamically controlled multileaf collimator with 40 leaves
that project on our accelerator to either 1.0 x 0.84 cm2 or 1.0 x 1.68 cm2 at
isocenter arranged in two banks of 20 leaves each. The dose-calculation algorithm
uses tissue-phantom ratios derived from percent depth dose measurements, measured
relative output data, and single leaf profiles. Some compromises are made in the
algorithm terms to enable more straightforward dosimetry measurements and to
reduce dose computation times. The dose calculation algorithm is presented, and
consequences of the approximations are investigated using previously published 4
MV photon beam data. RESULTS: Most of the approximations lead to dose errors of a
few percent. However, the use of depth-invariant single-leaf profiles results in
errors as large as 9% for 4 MV fixed beams. CONCLUSIONS: Large dosimetric errors
are possible for small fixed fields using this algorithm. However, the algorithm
is designed for tomotherapy dose delivery, where doses are delivered from
multiple directions and depths. Investigations of the algorithm in more
clinically relevant conditions have been conducted and show that the algorithm
accuracy is 1.3% and therefore is clinically acceptable for tomotherapy.
PMID- 9652861
TI - Improvement of CT-based treatment-planning models of abdominal targets using
static exhale imaging.
AB - PURPOSE: CT-based models of the patient that do not account for the motion of
ventilation may not accurately predict the shape and position of critical
abdominal structures. Respiratory gating technology for imaging and treatment is
not yet widely available. The purpose of the current study is to explore an
intermediate step to improve the veracity of the patient model and reduce the
treated volume by acquiring the CT data with the patients holding their breath at
normal exhale. METHODS AND MATERIALS: The ventilatory time courses of diaphragm
movement for 15 patients (with no special breathing instructions) were measured
using digitized movies from the fluoroscope during simulation. A subsequent
clinical protocol was developed for treatment based on exhale CT models. CT scans
(typically 3.5-mm slice thickness) were acquired at normal exhale using a spiral
scanner. The scan volume was divided into two to three segments, to allow the
patient to breathe in between. Margins were placed about intrahepatic target
volumes based on the ventilatory excursion inferior to the target, and on only
the reproducibility of exhale position superior to the target. RESULTS: The
average patient's diaphragm remained within 25% of the range of ventilatory
excursion from the average exhale position for 42% of the typical breathing
cycle, and within 25% of the range from the average inhale position for 15% of
the cycle. The reproducibility of exhale position over multiple breathing cycles
was 0.9 mm (2sigma), as opposed to 2.6 mm for inhale. Combining the variation of
exhale position and the uncertainty in diaphragm position from CT slices led to
typical margins of 10 mm superior to the target, and 19 mm inferior to the
target, compared to margins of 19 mm in both directions under our prior protocol
of margins based on free-breathing CT studies. For a typical intrahepatic target,
these smaller volumes resulted in a 3.6% reduction in Veff for the liver.
Analysis of portal films shows proper target coverage for patients treated based
on exhale modeled plans. CONCLUSIONS: Modeling abdominal treatments at exhale,
while not realizing all the gains of gated treatments, provides an immediate
reduction in the volume of normal tissue treated, and improved reliability of
patient data for NTCP modeling, when compared to current "free breathing" CT
models of patients.
PMID- 9652862
TI - A little to a lot or a lot to a little: is NTCP always minimized in multiport
therapy?
AB - PURPOSE: We address the question of whether or not, for the same average (or
integral) dose, a smaller uniform dose to an entire normal tissue structure
always results in a lower normal tissue complication probability (NTCP) than does
a proportionally larger dose to a partial volume of the same structure. METHODS
AND MATERIALS: A recent compilation of NTCP data and two theoretical formulations
of the dependence of NTCP on dose and partial volume irradiated-the Lyman probit
equation and the binomial model-are used to examine this question. Both models
fit equally well available NTCP data. RESULTS: Empirical data indicate that for
lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given
a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating
a partial volume fraction rather than the entire normal organ. The binomial model
supports this interpretation, whereas the probit model predicts that for all
organs uniform irradiation of the whole organ always results in the lowest
possible NTCP. CONCLUSIONS: In contrast to what is commonly believed, this study
suggests that for at least two normal tissues, namely lung and kidney, there may
be situations where "a lot to a little" (i.e., fewer treatment ports) will result
in higher tumor control probability and better treatment plan than "a little to a
lot" (i.e., multifield treatment). This finding, which is independent of the
binomial or probit models used here, depends only on the accuracy of the
empirical NTCP data. It is also interesting to note that: a) lung and kidney are
commonly classified as parallel tissues, while the others have more of a serial
architecture; and b) the choice of the NTCP model can have a profound impact on
treatment planning decisions.
PMID- 9652863
TI - A simple method to verify in vivo the accuracy of target coordinates in linear
accelerator radiosurgery.
AB - PURPOSE: A simple method that verifies the coincidence of the isocenter with the
center of the target volume in radiosurgery treatment conditions is described.
The accuracy is compared to that of accepted computerized procedures employing
fiducial markers. METHODS AND MATERIALS: The center of the beam is identified by
a cylindrical localizer, fixed to the plate of the supplemental collimator, with
a 2 x 50 mm tungsten rod coincident with the beam axis and is projected onto the
x-ray portal verification films. Prior to irradiation, the coordinates of the
intersection of the beams axes, which is in a known spatial relationship with the
isocenter, are read directly on portal x-ray films and their coincidence with the
coordinates set during patient positioning, is checked. RESULTS: The mean
displacement in AP, Lat, and Vert coordinates respectively, over 84 patients,
between the coordinates calculated by the computerized procedure employing
fiducial markers and the coordinates calculated by using the rulers was 0.3 +/-
0.4 mm. CONCLUSIONS: From the results obtained with the two methods we can
conclude that rulers method can be used as a fast indirect control of the
position of the radiation isocenter. Moreover, the dimensions of the radiation
field and the correct alignment of the tertiary circular collimator can be also
documented.
PMID- 9652864
TI - Optimal image resolution for digital storage of radiotherapy-planning images.
AB - PURPOSE: To evaluate the quality of digitized radiation-planning images at
different resolution and to determine the optimal resolution for digital storage.
METHODS AND MATERIALS: Twenty-five planning films were scanned and digitized
using a film scanner at a resolution of 72 dots per inch (dpi) with 8-bit depth.
The resolution of scanned images was reduced to 48, 36, 24, and 18 dpi using
computer software. Image qualities of these five images (72, 48, 36, 24, and 18
dpi) were evaluated and given scores (4 = excellent; 3 = good; 2 = fair; and 1 =
poor) by three radiation oncologists. An image data compression algorithm by the
Joint Photographic Experts Group (JPEG) (not reversible and some information will
be lost) was also evaluated. RESULTS: The scores of digitized images with 72, 48,
36, 24, and 17 dpi resolution were 3.8 +/- 0.3, 3.5 +/- 0.3, 3.3 +/- 0.5, 2.7 +/-
0.5, and 1.6 +/- 0.3, respectively. The quality of 36-dpi images were definitely
worse compared to 72-dpi images, but were good enough as planning films.
Digitized planning images with 72- and 36-dpi resolution requires about 800 and
200 KBytes, respectively. The JPEG compression algorithm produces little
degradation in 36-dpi images at compression ratios of 5:1. CONCLUSION: The
quality of digitized images with 36-dpi resolution was good enough as radiation
planning images and required 200 KBytes/image.
PMID- 9652865
TI - Monte Carlo-based dose-rate tables for the Amersham CDCS.J and 3M model 6500
137Cs tubes.
AB - PURPOSE: (1) To present reference-quality dose-rate distributions for the
Amersham CDCS.J-type 137Cs intracavitary source (hitherto unavailable in the
literature) and updated tables for the 3M model 6500/6D6C source. (2) To assess
the accuracy of the widely used 1D pathlength (Sievert integral) algorithm for
lightly filtered 137Cs tube sources. METHODS AND MATERIALS: A Monte Carlo photon
transport code is used to calculate the dose-rate distributions about the 3M
source and the CDCS.J source based on radiographic examination of the sources and
the vendors' specifications. Dose-rate distributions are provided in the form of
Cartesian "away-and-along" lookup tables. Using a general form of the Sievert
integral, calculated dose-rate distributions were compared to the Monte Carlo
benchmark calculations treating the filtration coefficients as best-fit
parameters as well as approximating them by linear energy absorption
coefficients. In addition, the errors introduced by approximating the active
source core by uniform cylinders or line sources was evaluated. RESULTS: The
Model CDCS.J dose distribution differs from that of the 3M model 6500 source by
5.9% to +14.4% (root-mean-square [RMS] average: 2.6%). The RMS accuracy of the
Sievert algorithm is 2.4% to 2.8% (error range of -1.4% to 7.6%) when filtration
coefficients for steel and ceramic media are approximated by linear energy
absorption coefficients. If the filtration coefficients are treated as parameters
of best fit, selected to minimize the discrepancies between 1D pathlength and
Monte Carlo calculations, the RMS error is reduced to 0.8% (error range of -1.8%
to 4.1%). The optimal values of stainless steel and low-density ceramic or glass
filtration coefficients are approximately independent of the source geometry.
CONCLUSIONS: The widely used Sievert integral algorithm accurately characterizes
the dose distribution around stainless-steel clad low-density matrix 137Cs
sources, particularly if design-independent best-fit values of the filtration
coefficients are used. Although both families of source designs studied produce
similar dose distributions, source-design specific dose distributions should be
used for clinical treatment planning and dose-algorithm validation.
PMID- 9652866
TI - Regarding cardiac function and morbidity in long-term survivors of Hodgkin's
disease.
PMID- 9652867
TI - Should we be using confidence intervals when reporting results of oncology
studies?
PMID- 9652868
TI - Regarding predicting radiation response.
PMID- 9652869
TI - Regarding Zagars and Pollack.
PMID- 9652870
TI - Predicting lung function after irradiation for lung cancer: comment on paper by
Marks et al.
PMID- 9652871
TI - Is the safety and efficacy of calcium antagonists now established?
PMID- 9652872
TI - Nifedipine after acute myocardial infarction--sola dosis facit venenum: only the
dose determines the harm.
PMID- 9652873
TI - The inappropriate use of hypothesis testing to infer safety of calcium channel
blockers.
PMID- 9652874
TI - Calcium channel blockers and the risk of cancer: a preclinical assessment.
AB - The preclinical evidence for a potential influence of calcium channel blockers
(CCBs) on carcinogenesis is discussed in the light of a broad database from
rodent carcinogenicity studies as well as literature data. In all bioassays
performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine,
nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential
of these compounds. Calcium is an essential intracellular signal for cell
proliferation and apoptosis. The crucial role of increased cell proliferation in
all stages of carcinogenesis is well documented. Some indirect experimental
evidence also points to a role of defective apoptosis in tumor promotion. CCBs
uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis
is inconsistent, resulting in an inhibition or increase in apoptosis dependent on
cell type. Accordingly, antitumorigenic effects of CCBs have been reported based
on their antiproliferative action. A tumor-promoting effect of CCBs based on
inhibition of apoptosis, however, remains purely speculative and, in fact, can be
denied based on the results of in vivo bioassays. It is therefore concluded that
there is no preclinical evidence that should give rise to concern over the
carcinogenic potential of dihydropyridine-type CCBs.
PMID- 9652875
TI - Long-term mortality follow-up of hospital survivors of a myocardial infarction
randomized to nifedipine in the SPRINT study. Secondary Prevention Reinfarction
Israeli Nifedipine Trial.
AB - This study was intended to determine the 5-year mortality of 2138 post-myocardial
infarction (MI) patients who took part in the Secondary Prevention Reinfarction
Israeli Nifedipine Trial (SPRINT). In the framework of the SPRINT study, 1065
patients were randomly assigned 30 mg/d nifedipine therapy, for a mean 10-month
follow-up period, and 1073 received placebo. No information is available
concerning treatment after the first year. One-year postdischarge mortality was
5.0% in the placebo group and 5.9% among patients receiving nifedipine (P =
0.37). Mortality rates after 5 years of follow-up in patients previously
randomized to 1 year of nifedipine therapy and placebo were 18.4% and 18.3%,
respectively. The 5-year mortality risk ratio associated with randomization to
nifedipine over 1 year, adjusted for age, gender, past MI, angina, diabetes,
hypertension, MI location, and therapy, was 1.00 (95% CI: 0.81-1.22). Our results
do not support an association between nifedipine therapy and a late harmful
effect on long-term mortality.
PMID- 9652876
TI - Nifedipine and cancer mortality: ten-year follow-up of 2607 patients after acute
myocardial infarction.
AB - Recent publications contended that the use of short-acting calcium antagonists
may double the risk of cancer incidence and possibly increase mortality in
hypertensive patients. The purpose of this study was to assess the risk ratio for
cancer mortality associated with nifedipine in a large population of patients
post-myocardial infarction. Cancer mortality data, over a 10-year period, were
obtained on 2607 hospital survivors of acute myocardial infarction who were
screened, but not included, in the Secondary Prevention Reinfarction Israeli
Nifedipine Trial (SPRINT I) study. In this group of patients, 526 (20%) were on
nifedipine, according to their treating physicians' decision. In the cohort of
screened patients not included in SPRINT I, there were 22 (4.2%) cancer-related
deaths in the patients on nifedipine compared with 114 (5.5%) in the group not
treated with nifedipine (P = 0.23). In multivariate analysis, the 10-year cancer
mortality risk ratio associated with nifedipine therapy was 1.06 (95% CI 0.52
2.18). The current analysis shows no evidence of an increased risk of cancer
mortality in a large number of patients treated at baseline with nifedipine.
PMID- 9652877
TI - Acute myocardial infarction mortality related to use of calcium antagonists
before admission to hospital.
AB - We investigated whether prior use of calcium antagonists in 80 (16.8%) out of 477
patients (64% males) admitted with acute myocardial infarction (MI) had any
impact on in-hospital mortality. Patients using calcium antagonists were slightly
older (74 years vs. 72 years, 2P = 0.039) than those not taking them and fewer
were male patients. Previous MI, diabetes mellitus, and prior use of aspirin,
beta-blockers, and long-acting nitrates were more frequent in patients on calcium
antagonists. In contrast, fewer patients on calcium antagonists prior to symptoms
received thrombolytic treatment (21.3% vs. 34.8%, 2P = 0.018). The study had an
observational exposed/nonexposed design, and we looked for both crude and
adjusted effects. Of the 83 patients (17.4%) who died during hospitalization, 18
patients were in the calcium antagonist group (22.5%). The odds ratio (OR) for
these patients to die in the hospital was 1.48 and the 95% confidence interval
(CI) 0.78-2.78; 2P = 0.19. When adjusting for confounders (gender, age, smoking
habit, previous MI, and diabetes mellitus, as well as prior use of aspirin, beta
blockers, long-acting nitrates, and thrombolytic treatment at entry) OR was 1.08
and 95% CI 0.57-2.05; 2P = 0.85. Thus, we found no excess in-hospital mortality
in patients with acute MI using calcium antagonists prior to the onset of
symptoms.
PMID- 9652878
TI - Adverse reactions to antihypertensive therapy.
AB - A large number of antihypertensive agents are available today. They belong to
different drug classes and permit the treating physician to choose the drug he
deems best suited for the treatment of an individual patient. Because
hypertension is usually asymptomatic yet requires long-term therapy,
consideration of potential undesirable effects of drugs used for its treatment is
important for making the appropriate choice. In this context, a precise
understanding of the typical adverse reaction profiles of the different drugs is
essential. This article provides a short review of the adverse reaction profiles
of the main classes of antihypertensive drugs and refers to topics such as the
recent controversy regarding calcium channel blockers and comparative
investigations between different antihypertensive agents. Furthermore, the
effects of antihypertensives on metabolic parameters, differences between their
effects in subgroups of patients and in patients with different concomitant
diseases, and the potential of antihypertensives for interactions with other
drugs are briefly discussed. Even with a good knowledge of all of these aspects,
however, no fixed plan for drug treatment of hypertension suitable for every
patient can be established. A high percentage of adverse drug reactions can,
however, be avoided by appropriate drug selection and dosage, carried out after
careful consideration of the known adverse reaction profiles as well as the known
spectrum of pharmacological actions of the different compounds. Low doses are
often effective and well tolerated. Instead of increasing the dose, it is usually
preferable to add a low dose of a second agent with a different mode of action if
one drug given alone does not sufficiently lower blood pressure. This procedure
avoids many adverse drug reactions attributable to an exaggerated pharmacological
response, and, if chosen carefully, this combination may also reduce
counterregulatory reactions secondary to the fall in blood pressure.
PMID- 9652879
TI - Selection of drug therapy in stable angina pectoris.
AB - Drug therapy in stable angina has two aims: the prevention of major cardiac
events (such as unstable angina, myocardial infarction, or death) and the control
of chest pain and transient myocardial ischemia. Given the low incidence of major
cardiac events in patients with stable angina, primary preventive studies are
scarce because they require a large sample size and long-term follow-up. Thus
far, only aspirin and some lipid-lowering agents have been shown to be effective
for this purpose. Antiischemic drugs reduce the imbalance between myocardial
oxygen demand and supply, either by reducing oxygen consumption or by increasing
coronary blood flow. The ideal approach would be to target drug therapy against
the ischemia-inducing factor in each patient. The characteristics of anginal
symptoms do not seem to help in selecting medical therapy, whereas a standard
exercise test and a provocative test of coronary vasoconstriction may provide
useful information in order to select patients who will preferentially respond to
either a beta-blocker or a calcium antagonist. The combination of two or more
anti-ischemic drugs does not seem to be any more effective than an adequately
titrated monotherapy in reducing the occurrence of myocardial ischemia in
individual patients. Combination therapy in stable coronary artery disease should
include an individually selected and optimally titrated anti-ischemic agent and
aspirin, with the addition of a lipid-lowering agent in patients with even mild
hypercholesterolemia.
PMID- 9652880
TI - Safety, tolerability, and neurohormonal changes of the combination captopril plus
losartan in the early postinfarction period: a pilot study.
AB - Suppression of formation of angiotensin II (A-II) is thought to be a major
contributor to the hemodynamic response to angiotensin-converting enzyme
inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may
rebound during ACE-in treatment. The study sought to verify the feasibility,
safety, and tolerability of the combination of captopril (75 mg/d) plus losartan
(25 mg/d). We also wished to establish whether the combination was able to avoid
the increase of angiotensin II resulting from losartan treatment in early
postinfarction phases of reperfused anterior acute myocardial infarction (AMI).
Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from
the onset of symptoms, suitable for thrombolysis (first episode), Killip class I
II and reperfused, receiving 75 mg/d of captopril within 3 days from admission,
and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind)
into two groups: Group A included 22 patients (6 women and 16 men) and received
captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men)
and received captopril 75 mg/d within 3 days from admission plus losartan 12.5
mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine
(NE) and A-II levels were measured on the 3rd and 10th days after admission. The
two groups were similar with regard to age, sex, creatinine kinase peak, ejection
fraction, end-systolic volume, and risk factors. Group B (captopril plus
losartan) showed a significant reduction of BP, from 124 +/- 8.5 mmHg to 108 +/-
6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 +/- 9
mmHg, and 10 days after admission BP was 118 +/- 11 mmHg. NE and A-II values did
not show significant differences in basal samples. At 10 days after admission
values were NE 298 +/- 90 versus 272 +/- 86 pg/mL and A-II 6.07 +/- 2.97 versus
5.29 +/- 2.05 pg/mL for the two groups. Our data suggest, for the first time,
that the combination of captopril plus losartan is feasible and does not produce
serious side effects. When losartan was added to ACE-in treatment, there was no
significant increase in A-II.
PMID- 9652881
TI - Increasing nitroglycerin release from patches enables circumvention of early
nitrate tolerance.
AB - Continuous treatment with transdermal nitroglycerin leads to tolerance
development within the first day of application. Effective long-term therapy can
be provided by interval treatment with nightly patch removal, but even during the
hours of intermittent patch application there is rapid attenuation of initial
effects. To assess whether an unattenuated antiischemic and antianginal efficacy
during the hours of intermittent dosing can be maintained, a modified drug
release profile with increasing plasma concentrations was evaluated using a
double-blind, placebo-controlled crossover protocol. Eleven patients with
documented coronary artery disease received, in a randomized order, a total of
four low-dose nitroglycerin patches (5 mg/24 h each) or placebo, respectively, at
intervals of 3 hours. After a treatment interval of 12 hours, all patches were
removed for an equally long patch-free interval prior to renewed application of
one patch the next morning. At a comparable workload, reductions of ST-segment
depression of 65%, 63%, and 56% were found at 2.5 hours, 8 hours, and 12 hours
after application of the first patch on day 1, respectively (all significant vs.
placebo; 2.5 hours vs. 12 hours, n.s.). On day 2, the comparable reduction of 63%
at 2.5 hours after renewed application indicates prevention of tolerance
development during subchronic treatment. Effects on exercise capacity and angina
pectoris paralleled those on exercise-induced ST-segment depression. Plasma
concentrations of nitroglycerin increased from 223 pg/mL to 558 and 803 pg/mL on
day 1 and amounted to 205 ng/mL at 2.5 hours on day 2. Thus, interval therapy
with increasing nitroglycerin concentrations provides unattenuated antiischemic
and antianginal efficacy during the hours of treatment and circumvention of early
tolerance during subchronic application. This modified pharmacokinetic profile
can be regarded as a model for an improved dosage regimen in nitrate interval
therapy.
PMID- 9652882
TI - Hip fracture prevention: a review.
AB - The incidence of hip fractures worldwide is expected to almost quadruple in the
next 60 years. Increased cost-containment pressures will focus attention not only
on improvements in hip fracture treatment but also on prevention. Three
approaches that can prevent hip fractures--preventing falls, preventing and
treating bone fragility, and using external hip protectors--are reviewed.
Although it is impossible to prevent all hip fractures, these methods may
significantly reduce the annual incidence of these fractures.
PMID- 9652883
TI - The short-term economic implications of prosthetic selection in hemiarthroplasty
of the hip.
AB - This retrospective study assessed the economic impact of prosthetic selection in
the treatment of displaced intracapsular fractures. The records of 28 patients
were divided into two groups: 16 patients who received an Austin-Moore,
nonmodular device and 12 patients (6 men and 6 women; mean age, 77 years) who
received a modular, bipolar device. The bipolar group had significantly greater
mean operative times, total charges for the device, and total charges for
supplies. Surgeons treating hip fractures should consider implant cost,
functional outcome, and patient demands when selecting a prosthesis for
hemiarthroplasty care.
PMID- 9652884
TI - Is there a relationship between hypertension and lower-extremity contracture
release in cerebral palsy?
AB - Recent reports have suggested a relationship between release of lower-extremity
contractures and the development of hypertension in cerebral palsy and
poliomyelitis patients. A retrospective study was performed on 119 cerebral palsy
patients who had undergone lower-extremity contracture releases. Temporary
elevation of systolic blood pressure in the perioperative and intraoperative
periods occurred in 46 patients (39%), and temporary elevation of diastolic blood
pressure occurred in 14 patients (12%). Type of cerebral palsy, patient age,
patient sex, type of anesthesia, and type of procedure were not significantly
correlated with the temporary blood pressure elevations. No patient developed
sustained elevation of systolic and diastolic blood pressure. We conclude that
lower-extremity contracture release in pediatric patients is not associated with
an increased incidence of postoperative hypertension.
PMID- 9652885
TI - The quantitative anatomy of the superior gluteal artery and its location.
AB - Twenty cadaveric posterior gluteal regions were dissected to quantitatively
determine the location and dimensions of the superior gluteal artery and its
branches on the posterior gluteal region. Two reference lines were defined: one
(transverse) was drawn from the posterior inferior iliac spine (PIIS) across the
ilium to the anterior superior iliac spine (ASIS), and another (vertical) was
drawn orthogonal to the transverse line at a point 8 cm from the PIIS. Results
showed that the average distances from the posterior superior iliac spine (PSIS)
and PIIS to the superior gluteal artery origin at the sciatic notch were 60 mm
and 42 mm, respectively. The deep superior branch traveled an average of 18 mm
above the transverse line at the vertical line, and averaged 54 mm from the iliac
crest at the same point. This same branch inserted in the medius an average of 29
mm from the ASIS, and 11 mm above the transverse line, while providing 4 to 7
perforators to the gluteus medius and 0 to 2 to the gluteus minimus. The deep
inferior branch traveled an average of 23 mm below the transverse line along the
vertical line and penetrated the minimus or medius 36 mm from the ASIS, while
providing 3 to 8 perforators to the medius and 1 to 3 to the minimus. The average
distance from the deep inferior branch to the superior edge of the acetabulum
along the vertical line was 25 mm. These data may be helpful in preventing the
injury of the superior gluteal artery during the posterior gluteal approach.
PMID- 9652886
TI - Spinal ligament loading during axial distraction: a biomechanical model.
AB - The objective of this study was to develop a method of measuring spinal ligament
forces during axial distraction to understand the load-bearing contributions of
the individual ligamentous structures in the lumbar spine. A sequential ligament
cutting technique and the arthroscopically implantable force probe (AIFP,
MicroStrain, Burlington, VT) were used to determine loading of the anterior
longitudinal ligament (ALL), the posterior longitudinal ligament (PLL), and the
remaining posterolateral complex (PLC) in an in vitro corpectomy model. During
axial spinal distraction, the relative percentages of the total axial load in the
individual structures were as follows: ALL, 37.5%; PLL, 17.2%; PLC, 45.3%.
PMID- 9652887
TI - The effect of a cardiac rehabilitation program on the joints and spine:
subjective evaluation.
AB - To examine the effects of a cardiac rehabilitation exercise program on the joints
of patients just recovered from a coronary disease episode, a questionnaire was
distributed to such patients entering the program. Of 171 patients who completed
the questionnaire, 76 indicated they had pain in some joints, most frequently in
the back. Sixty-six patients were available to complete follow-up questions after
participating in the exercise program for a minimum of 3 months. Pain, or lack
thereof, remained unchanged in 35 participants. A decrease in pain was noted by
27, and more pain by 4.
PMID- 9652888
TI - Condensing osteitis of the clavicle: case report and review of the literature.
AB - Osteitis condensans of the clavicle is a rare condition characterized by pain in
the shoulder and often limitation of motion of the shoulder. The medical history
and results of the physical examination, laboratory data, and radiographic
studies (including computed tomography and magnetic resonance imaging), often
establish the diagnosis. Patients who have slight or no pain usually require no
treatment. Varying results have been reported for many different methods of
treatment, including surgical excision, chemotherapy, antibiotics, nonsteroidal
anti-inflammatory medications, radiation, local corticosteroid injection, and
physical therapy. A typical case report and the differential diagnosis for
condensing osteitis of the clavicle are presented.
PMID- 9652889
TI - Aberrant position of the ulnar nerve and artery overlying the carpal canal.
AB - Many anomalies of the ulnar nerve and artery within the wrist have been
described. We report the first known case of the ulnar nerve and artery overlying
the midportion of the transverse carpal canal, leaving Guyon's canal empty. This
anomaly has considerable consequences for surgeons considering endoscopic carpal
release, because the ulnar nerve and artery are at significant risk of injury.
PMID- 9652890
TI - Synovitis secondary to giardiasis in children.
AB - Giardia lamblia, a gastrointestinal protozoan, is one of the most common disease
causing parasites in the world. Giardiasis is primarily encountered in areas with
poor sanitation, but it is also seen in more developed countries. A possible
sequela of Giardia infections of the bowel is reactive arthritis or synovitis.
Few reports of synovitis secondary to giardiasis exist in the literature.
Arthropathy secondary to giardiasis is uncommon, but may be underdiagnosed. In
this study, Giardia synovitis was diagnosed in two children at a major children's
hospital over a 20-year period. Both were boys, aged 7 years, 6 months and 1
year, 8 months at the time of presentation. The knee was the affected joint in
both patients, and both cases were initially misdiagnosed as septic arthritis.
The synovitis subsided with treatment of the giardiasis, one with cefuroxime and
the other with cefuroxime and metronidazole. The diagnosis of Giardia synovitis
should be suspected by the presence of Giardia cysts in the stool, similar
symptoms in other family members, a synovial white count under 40,000, and an
increase in the eosinophil count. Although uncommon, giardiasis can cause severe
synovitis that may be confused with a septic joint.
PMID- 9652891
TI - Ultrasound for the diagnosis of retained splinters in the soft tissue of the
hand.
AB - Foreign material may present both a diagnostic and a surgical problem. Most
irretrievable foreign bodies are wood and are radiolucent. Ultrasound offers an
alternative way of preoperative imaging in these situations. We describe four
cases of retained splinters in the hand that were localized with sonography and
subsequently removed surgically. This report supports the reliability and
efficiency of ultrasound as the primary imaging tool for the detection of foreign
bodies if conventional radiographs are negative. Preoperative sonographic
localization of the foreign body may be extremely useful to the surgeon and may
minimize surgical dissection and operating room time.
PMID- 9652892
TI - Midshaft femoral fracture, concomitant ipsilateral hip joint injury, and
disruption of the knee extensor mechanism: a unique triad of dashboard injury.
AB - Our experience with 10 patients who suffered midshaft fractures of the femur and
injuries to their ipsilateral hips has resulted in a treatment protocol that we
believe can avoid unnecessary complications. The surgical protocol is a three
stage procedure based on (1) intramedullary nailing of the femur with
interlocking for preserving the anatomic length and rotation of the femur; (2)
treatment of the hip joint injury by means of open reduction and internal
fixation of the acetabular fracture and/or reduction and fixation of the
fractured femoral neck; and (3) repair of the extensor mechanism. Eight patients
received this treatment and had fast recoveries. Union of the femoral fracture
and full range of motion of the knee joint were observed within 3 months. In
contrast, two patients who had received different surgical treatment had
incomplete functional recoveries. This study offers a treatment protocol for
ipsilateral disruption of the extensor mechanism, hip joint injury, and midshaft
fracture of the femur in the multiply injured patient that can achieve full
recovery with no complications. This relatively rare combination of injuries is
definitely worthy of special attention.
PMID- 9652893
TI - Entry point of reconstruction nail.
AB - If the femoral neck is involved in a pathological process, the surgeon may avoid
a base neck entry for the reconstructive nail. If a trochanteric entry is
selected, the surgeon must be aware that the nail has to be driven more distally
in order to place the neck screws properly. Violation of the knee joint is a
consideration, and so is varus malposition.
PMID- 9652894
TI - Errors in sex differentiation.
PMID- 9652895
TI - Preferential use of branched-chain amino acids as an energy substrate in patients
with liver cirrhosis.
AB - We analyzed basal energy metabolism in 20 healthy volunteers and 41 cirrhotic
patients by indirect calorimetry. Subjects were then given either glucose,
branched-chain amino acids (BCAA) or fatty acids as an energy substrate. Resting
energy expenditure (REE), nonprotein respiratory quotient (npRQ), and oxidation
rates of glucose (% CHO), protein (% PRO) and fat (% FAT) were analyzed. REE and
%FAT were significantly higher and % CHO and %PRO were significantly lower in
cirrhosis than in controls. These changes correlated with disease severity.
Glucose and BCAA were utilized efficiently as energy substrates and reduced %FAT
in cirrhosis. Energy efficacy (increased energy expenditure/energy equivalent of
the supplemented nutrient) was significantly higher in BCAA (96 +/- 16%) than in
glucose (41 +/- 8%) (p<0.01) and fatty acids (27 +/- 13%) (p<0.05). Patients with
cirrhosis have an increased energy requirement. BCAA seems to be the preferred
substrate to meet this demand, because its energy efficacy is higher than glucose
or fatty acids in cirrhosis.
PMID- 9652896
TI - Eradication of Helicobacter pylori restores elevation of serum gastrin
concentrations in patients with end-stage renal disease.
AB - In order to explore the role of Helicobacter pylori (H. pylori) infection in
hypergastrinemia in patients on dialysis, the changes in serum gastrin
concentration were examined before and after eradication treatment for H. pylori.
Twenty-seven patients on dialysis were treated for the eradication of H. pylori.
Fasting serum gastrin concentrations were measured by a radioimmunoassay which
detects gastrin 17. Ammonia and pH levels of the gastric juice were also
measured. The serum gastrin concentrations were significantly decreased following
eradication of H. pylori, and the mean value reached the normal range. The
restoration of hypergastrinemia was associated with marked reductions of gastric
juice ammonia and pH levels. In contrast, patients in whom H. pylori was not
eradicated showed no changes in these parameters. In conclusion, the elevation of
the fasting serum gastrin 17 concentration seen in dialysis patients appeared to
be attributable to H. pylori infection in the stomach.
PMID- 9652897
TI - Hereditary angioneurotic edema and thromboembolic diseases: I: How symptoms of
acute attacks change with aging.
AB - Localized edema of the larynx and pharynx leading to death from asphyxia has long
been recognized as a characteristic symptom of hereditary angioneurotic edema
(HANE). Long-term follow-up of younger HANE patients has revealed that transient
localized acute attacks of edema affect tissues where the microcirculation
maintains the blood supply. However, with aging, HANE attacks precipitate
disseminated intravascular coagulation (DIC) or multiple organ failure (MOF).
Substitution with a C1-inhibitor (C1-INH) has resulted in a fulminant lethal end
with a rapid and profound decrease in antithrombin-III (AT-III) activity. A
possible mechanism is as follows: Exogenous stimuli activate plasma proteinase
systems with the generation of plasma kallikrein that activates the tissue factor
pathway (TF) and liberates bradykinin (BK). In younger patients, BK enhances
vascular permeability. In the elderly, activated TF is controlled by tissue
factor pathway inhibitor (TFPI) and generates thrombin, which is the target
enzyme of AT-III and precipitates DIC or MOF. In elderly patients, the
characteristic symptom of HANE is hypercoagulation by age-related changes in the
biosynthesis of AT-III or TFPI.
PMID- 9652898
TI - Efficacy of a low-dose subcutaneous lisuride infusion in Parkinson's disease.
AB - Five parkinsonian patients with motor fluctuations and dyskinesia after long-term
treatment with levodopa were treated with subcutaneous lisuride infusion (0.24
0.42 mg/day) together with oral levodopa for a mean period of 27 (range 13-36)
months. All 5 patients showed marked initial improvement in mobility. Mild
psychiatric side effects were observed in three patients; however, these side
effects disappeared with reduction in the dosage of lisuride to 0.06 mg per day
without a significant increase in motor fluctuations. A low dose of subcutaneous
lisuride infusion with oral levodopa is an effective treatment for fluctuations
of motor performance in parkinsonian patients without adverse psychiatric
effects.
PMID- 9652899
TI - Hepatic and splenic sarcoidosis evaluated by multiple imaging modalities.
AB - We present a case of hepatosplenic sarcoidosis. A 51-year-old Japanese male, who
was diagnosed to have sarcoidosis 4 years previously, was presented to our
hospital because of dry cough and anorexia with weight loss. He had tender
hepatosplenomegaly. A dynamic abdominal computed tomography (CT) revealed
multiple small low-density areas in both liver and spleen, as well as in magnetic
resonance imaging (MRI). The laparoscopic photographs showed many small whitish
nodules surfacing on the liver and several tumorous nodules on the spleen.
Multiple imaging modalities including dynamic CT and MRI are valuable for
detecting focal hepatic and splenic lesions of sarcoidosis.
PMID- 9652900
TI - Diabetes mellitus accompanied by nonocclusive colonic ischemia.
AB - A 70-year-old man with diabetic triopathy was hospitalized with left lower
quadrant abdominal pain and tenderness, muscle guarding and absent bowel sounds.
Three hours after admission, creatine phosphokinase (CPK) was elevated and an
abdominal plain film X-ray showed intestinal gas retention, indicating paralytic
ileus due to inferior mesenteric artery occlusion. Urokinase (60,000 units/day)
and heparin (10,000 units/day) were administered. Angiography showed no occlusion
in the mesenteric artery. On the 16th day, the abdominal signs had disappeared
and CPK was normalized. We diagnosed this case as nonocclusive colonic ischemia
because of the hemorheological abnormalities due to diabetic triopathy and the
hypercoagulable state.
PMID- 9652901
TI - Apical hypertrophy with massive myocardial fibrosis: comparison with
electrocardiographic changes.
AB - We report the case of a 48-year-old woman with apical hypertrophy with massive
myocardial fibrosis. She was admitted to our hospital because of general malaise.
Echocardiographic examination showed asymmetrical apical hypertrophy, and an
electrocardiogram showed a giant negative T wave on V3-V6. Right ventricular
endomyocardial biopsy revealed massive myocardial fibrosis. Apical hypertrophy
can lead to disorders that vary in severity, including rare massive myocardial
fibrosis.
PMID- 9652902
TI - Malignant lymphoma demonstrating sick sinus syndrome.
AB - We report a case of T-cell-rich large B-cell lymphoma demonstrating sick sinus
syndrome as a single initial symptom, followed by the retention of pericardial
and pleural effusions. Intrapleural administration of interferon-alpha prevented
reaccumulation of the pleural effusion for one and a half months, whereas
systemic chemotherapy failed to control tumor growth in the skin and lymph nodes.
The autopsy revealed involvement of the sinoatrial node of the heart by lymphoma
cells.
PMID- 9652903
TI - A rare case of 46,XX true hermaphroditism with hidden mosaicism with sex
determining region Y chromosome-bearing cells in the gonads.
AB - The sex-determining region Y chromosome (SRY) triggers testis determination. We
report a 46,XX true hermaphrodite who had ambiguous genitalia at birth. A
laparotomy at one year of age revealed this patient to have a testis on the right
side and an ovotestis on the left side. By polymerase chain reaction analysis no
SRY was detected in the DNA from the leukocytes but it was found in the DNA from
the ovotestis. The hidden mosaicism with the Y-bearing cells in the gonads is
likely the cause of the dual gonads in this patient.
PMID- 9652904
TI - A hypopituitary patient who attained tall stature without growth hormone.
AB - We describe an unusual patient with hypopituitarism who attained tall stature
even without growth hormone (GH). A 37-year-old man was devoid of secondary
sexual characteristics, but manifested tall stature with a eunuchoidal feature.
Serum levels of GH, insulin-like growth factor-I, gonadotropins and testosterone
were all below normal. GH secretion was not enhanced by any provocative stimulus.
Adrenocorticotropic hormone increased after administration of corticotropin
releasing hormone, but not after insulin-induced hypoglycemia. Thyrotropin
increased in response to thyrotropin releasing hormone, but both free T3 and T4
did not rise. Magnetic resonance imaging disclosed a transected pituitary stalk.
The present patient had hypopituitarism due to perinatal problems but had grown
with the aid of non-GH growth-promoting factors, which suggests that man may be
able to achieve statural growth even without GH.
PMID- 9652905
TI - Malignant insulinoma with extensive liver metastases presenting as disturbance of
consciousness.
AB - A 56-year-old man was referred to our hospital for evaluation of episodic
disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's
triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline
insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver
metastases were found by abdominal computed tomography (CT). Based on the finding
of liver biopsy, the final diagnosis was malignant insulinoma with liver
metastasis. He selected conservative treatment and no hypoglycemic crisis has
occurred for one year since discharge. Early diagnosis and long-term follow-up is
necessary since this tumor is slow growing.
PMID- 9652906
TI - Multiple diffuse fibrosarcoma of bone associated with extramedullary
hematopoiesis.
AB - We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year
old man, was referred to our hospital with knee pain, anemia and
thrombocytopenia. No solid mass was seen on radiographic examination of the
kneejoint, but magnetic resonance imaging showed hypointensity of the distal
femur. Femoral biopsy revealed proliferation of long spindle-shaped fibrosarcoma
cells, while a bone marrow biopsy of iliac bone (which appeared normal on
radiographic examinations) showed replacement of hematopoietic cells by
fibroblast-like spindle cells. A diagnosis of multiple diffuse fibrosarcoma of
bone was therefore made. Autopsy revealed tumor invasion into multiple bones and
several visceral organs and extramedullary hematopoiesis in the liver, spleen and
lymph nodes. As this patient had leukoerythroblastic anemia with poikilocytosis,
splenomegaly exhibiting extramedullary hematopoiesis, and apparent fibrotic
change in his bone marrow, we suggest that this extremely rare disease should be
considered in the differential diagnosis of myelofibrosis.
PMID- 9652907
TI - Systemic mastocytosis with extensive polypoid lesions in the intestines;
successful treatment with interferon-alpha.
AB - A 35-year-old female presented in 1989 with hepatosplenomegaly, but no conclusive
diagnosis was established. From 1992, she experienced transient episodes of
facial flushing and palpitations. Osteosclerotic change was detected
radiologically. Colonoscopy revealed massive polypoid lesions. Mast cells were
demonstrated in bone marrow smear and imprinted preparations of colon biopsy
specimens by toluidine blue staining. Plasma concentrations of histamine and
soluble c-kit were elevated. She was successfully treated with interferon-alpha
and prednisolone, resulting in the disappearance of histamine-related attacks and
a gradual decrease in tumor size. However, the remission was interferon dose
dependent. This case was considered as systemic mastocytosis with massive
polypoid colon lesions and showed the importance of maintenance therapy with
interferon-alpha.
PMID- 9652908
TI - Double infection with Giardia lamblia and Salmonella paratyphi A associated with
acute renal failure.
AB - While traveling in India, a previously healthy twenty-year-old man had febrile
diarrhea. The patient was prescribed medical therapy, and all symptoms were
resolved. Fourteen days later, however, similar symptoms recurred. The patient
was admitted to a local hospital, but was transferred to our department because
of oliguria. Salmonella paratyphi A was isolated from blood and stool specimens,
and Giardia lamblia was identified in his stool. The patient's condition was
complicated by acute renal failure. The patient received tosufloxacin and
metronidazole. Renal function recovered completely without hemodialysis.
Paratyphoid fever and giardiasis were resolved. It is suggested that giardiasis
exacerbated the paratyphoid fever.
PMID- 9652909
TI - Na+, K+-ATPase inhibitor, ouabain accentuates irradiation damage in human tumour
cell lines.
AB - Two normal, two tumour, one transformed fibroblast cell line established from
Ataxia telangiectasia (AT) patients and one corrected AT hybrid were
characterised with regard to alpha, beta, SF2, and D values. Survival of 60Co
gamma-irradiated tumour and transformed cells was markedly reduced when the Na+,
K+-ATPase inhibitor ouabain was present 1 hr before and 3 hr post irradiation.
Under these conditions, the radiosensitivity in normal cells remained virtually
unchanged. Suppression of repair was found to play a role in the ouabain-induced
inhibition of the cell survival. In A549 lung carcinoma cells, addition of 10(-8)
M ouabain decreases the sublethal damage recovery ratio from 56.5 to 13.3. The
same drug concentration decreases the recovery ratio in L132 epithelial cells
only from 5.1 to 4.9. The fast repair component, as measured over the first 1.5
hr after irradiation, decreases from 1.83 to 0.36 hr(-1) in A549 cells and from
0.35 to 0.16 hr(-1) in HeLa cells. For 2 Gy fractions, the presence of 10(-8) M
ouabain 1 hr before irradiation and 3 hr after irradiation induces dose
enhancement ratios of 1.15-1.5. A more pronounced effect on cell inactivation may
be expected from multiple fractions. The concentrations required to downregulate
sublethal damage repair fall within the range where cardiac glycosides are used
clinically. Application of these drugs in radiotherapy thus seems feasible.
PMID- 9652910
TI - Measurement of proliferation activities in human tumor models: a comparison of
flow cytometric methods.
AB - Proliferating cells in tumors may be of considerable relevance in cancer therapy.
Not only do such cells dictate the rate of tumor progression, but evidence exists
that they may also play an important role in the diagnosis and prognosis of tumor
regrowth. Consequently, the identification of this subset of cells in the overall
neoplastic cell population is of considerable importance. The aim of the present
investigations was to compare four flow cytometric methodologies commonly used to
study cell proliferation. These included nuclear antigen Ki67 detection, acridine
orange (AO) and bromodeoxyuridine (BrdUrd) staining, and percent S-phase
determinations. Three human tumor cell lines (HEp3, A549, H226) were examined in
various stages of growth. Further, a direct comparison was made of the
proliferation activities of HEp3 cells grown in culture or as xenografts in nude
mice. The results showed that of the techniques investigated, detection of the
nuclear antigen Ki67 may be most useful for marking proliferating tumor cells and
determining tumor growth fractions.
PMID- 9652911
TI - Computed tomographic evaluation of radiation pneumonitis in a canine model.
AB - The objective of this study was to document the utility of computed tomography
(CT) and a three-dimensional (3-D) radiotherapy treatment planning system for
assessing the development of acute radiation pneumonitis in a canine model.
Fourteen dogs were randomly assigned to a nonirradiated control group or one of
three radiation dose groups receiving a single fraction of either 12, 15, or 18
Gy delivered to two-thirds of the right hemithorax. CT and survey radiographs
were performed in all dogs prior to and at defined intervals for up to 13 weeks
following irradiation. All images were subjectively evaluated for development of
radiation pneumonitis and CT images were quantitatively analyzed. Radiation
pneumonitis was detected earlier with CT images than with radiographs.
Quantitatively, functional lung volume and radiation pneumonitis lesion volume on
CT images changed over time in all irradiated dogs. However, there was no
statistically significant difference between the three radiation dose groups, but
a marked difference between irradiated dogs and nonirradiated controls. These
data suggest that CT is superior to survey radiography for the evaluation and
quantification of acute radiation pneumonitis in this canine model.
Quantification of acute radiation pneumonitis suggests future promise for
evaluating the efficacy of modifiers to lessen the effects of irradiating normal
lung tissue in this canine model.
PMID- 9652912
TI - Acute urinary morbidity following I-125 interstitial implantation of the prostate
gland.
AB - The objective of this paper was to evaluate the acute urinary morbidity
associated with I-125 interstitial implantation of the prostate gland. From 1991
1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate
gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75
Gy). The patients' urinary symptoms were recorded pre-implantation and at regular
intervals after implantation using the International Prostate Symptom Score
(IPSS), a self-assessment questionnaire in which patients scored 7 symptoms:
incomplete emptying, frequency, intermittency, urgency, weak stream, straining,
and nocturia. Median follow-up was 12 months. The natural history of implant
related urinary symptoms was assessed in this manner. In addition, dosimetric
factors including U/S prostate volume, total activity, activity per seed, dose
volume histogram (DVH) values for dose to gland, and dose area histogram (DAH)
values for dose to urethra and bladder were examined for correlation to the
severity of each symptom as well as to total IPSS (sum of the individual symptom
scores). Total IPSS peaked at 1 month post-implant and gradually returned to
approximately baseline at 24 months. Total IPSS directly correlated with total
activity and DVH for the prostate. Total IPSS, however, did not correlate with
bladder or urethral DAH. With the exception of frequency, individual symptoms did
not correlate with dose to gland, bladder, or urethra. Frequency scores did,
however, correlate not only with dose to prostate gland but also dose to urethra.
The acute urinary side effects of I-125 prostate implantation are transient and
peak at 1 month post-implant. The severity of the urinary irritative symptoms
developed are closely related to total dose to the gland. Urethral dose appears
to affect frequency most significantly. Urinary symptoms, therefore, may be a
limiting factor when considering dose escalation with I-125.
PMID- 9652913
TI - Clinical in vivo dosimetry using optical fibers.
AB - Discoloring of glass due to ionizing radiation depends on the absorbed dose. The
radiation-induced light attenuation in optical fibers may be used as a measure of
the dose. In high-energy photon beams (6 MV X rays), a lead-doped silica fiber
can be calibrated. A dosimeter based on an optical fiber was developed for
applications in radiation therapy. The diameter of the mounted fiber is 0.25 mm,
whereas the length depends on the sensitivity required. To demonstrate the
applicability, a customized fiber device was used to determine scattered
radiation close to the lens of the eye. Measurements were compared with TLDs
(LiF) in an anthropomorphic phantom. The comparison with TLD measurements shows
good agreement. In contrast to TLD, optical fibers provide immediate dose values,
and the readout procedure is much easier. Owing to its small size and diameter,
interesting invasive dose measurements are feasible.
PMID- 9652914
TI - A.W. Liley Prize 1997 awarded to Prof. Erich Saling, MD, Berlin.
PMID- 9652916
TI - Computer assisted learning.
PMID- 9652915
TI - A single site on the epsilon subunit is responsible for the change in ACh
receptor channel conductance during skeletal muscle development.
PMID- 9652917
TI - Appointment of consultants.
PMID- 9652918
TI - Good undergraduate teaching.
PMID- 9652919
TI - Lyme disease vaccine given guarded approval in the US.
PMID- 9652920
TI - Retraction. Evidence of unmet need in the care of physically disabled adults.
PMID- 9652921
TI - Dealing with research misconduct in the United Kingdom. Conduct unbecoming--the
MRC's approach.
PMID- 9652922
TI - Dealing with research misconduct in the United Kingdom. An editor's response to
fraudsters.
PMID- 9652923
TI - Dealing with research misconduct in the United Kingdom. Deception: difficulties
and initiatives.
PMID- 9652924
TI - Dealing with research misconduct in the United Kingdom. Honest advice from
Denmark.
PMID- 9652925
TI - What should a junior doctor have done?
PMID- 9652926
TI - You cannot expect people to be heroes.
PMID- 9652927
TI - Put out the fire or risk an inferno.
PMID- 9652928
TI - Present system of whistleblowing is unsatisfactory.
PMID- 9652929
TI - Research assessment exercise. Some of author's suggestions were misleading.
PMID- 9652930
TI - Research assessment exercise. Departments do not know rules of exercise.
PMID- 9652931
TI - Research assessment exercise. Exercise has implications for clinical academic
medicine.
PMID- 9652932
TI - Measles, measles vaccination, and Crohn's disease. Crohn's disease has not
increased in Finland.
PMID- 9652933
TI - Measles, measles vaccination, and Crohn's disease. Age specific prevalences do
not suggest association with in utero exposure.
PMID- 9652934
TI - Milk intake and bone mineral acquisition in adolescent girls. Adding milk to
adolescent diet may not be best means of preventing osteoporosis.
PMID- 9652935
TI - Milk intake and bone mineral acquisition in adolescent girls. Results in two
groups are not so different.
PMID- 9652936
TI - Resuscitation. Some aspects of 1997 guidelines are less helpful than old
guidelines.
PMID- 9652937
TI - Resurgence of interest in medical oaths and codes of conduct. Killing can never
be morally acceptable.
PMID- 9652938
TI - The "Diana effect". Number of inappropriate hospital admissions increased.
PMID- 9652939
TI - The "Diana effect". There was no "Diana effect" on numbers of psychiatric
emergencies.
PMID- 9652940
TI - Approval given for trials of AIDS vaccine.
PMID- 9652941
TI - MMR vaccination and autism 1998. Medical practitioners need to give more than
reassurance.
PMID- 9652942
TI - MMR vaccination and autism 1998. Those giving MMR vaccine had no input into
editorial.
PMID- 9652943
TI - The health of Gypsies. Governments and Roma communities must help to improve
outlook for Gypsies.
PMID- 9652944
TI - Exceptionalism in HIV. Past experience has been ignored.
PMID- 9652945
TI - Audit commission tackles anaesthetic services. Non-physician anaesthetists may
free up consultants to concentrate on patients requiring special attention.
PMID- 9652946
TI - Audit commission tackles anaesthetic services. Quoted paper did not say that
participation of nurses makes adverse outcomes more common.
PMID- 9652947
TI - Audit commission tackles anaesthetic services. Investment is required to increase
number of consultant anaesthetists.
PMID- 9652948
TI - Urgency and priority models. Distinction between urgency and priority helps no
one.
PMID- 9652949
TI - Providing letters to patients. GPs can be given copies of letters sent to
patients.
PMID- 9652950
TI - Providing letters to patients. Letters should be used carefully.
PMID- 9652951
TI - Providing letters to patients. Summary letters may be especially appropriate
after emergency admissions.
PMID- 9652952
TI - [Conference on problems of apoptosis. Moscow, 14-16 October 1996].
PMID- 9652953
TI - Kinetic and thermodynamic principles determining the structural design of ATP
producing systems.
AB - It is theoretically analysed whether the structural design of ATP-producing
pathways, in particular the design of glycolysis, may be explained by
optimization principles. On the basis of kinetic and thermodynamic principles
conclusions are derived concerning the stoichiometry of these pathways in states
of high ATP production rates. One of the extensions to previous investigations is
that the concentrations of the adenine nucleotides are taken into account as
variable quantities. This necessitates the consideration of an interaction of the
ATP-producing system I with an external ATP-consuming system II. A great variety
of pathways is studied which differ in the number and location of ATP-consuming
reactions, ATP-producing reactions and reactions involving inorganic phosphate.
The corresponding number of possible pathways may be calculated in an explicit
manner as a function of the number of those reactions which do not couple to ATP
or inorganic phosphate. The kinetics of the individual reactions are described by
linear or bilinear functions of reactant concentrations and all rate equations
are expressed in terms of equilibrium constants and characteristic times. A
thermo-dynamical analysis of the two coupled systems yields upper and lower
limits for the concentration of ATP and an explicit expression for the maximal
difference between the number of ATP-producing and ATP-consuming reactions of
system I. The following results of the optimization are obtained. (i) The ATP
production rate always increases if the ATP-producing reactions as well as those
reactions characterized by an uptake of inorganic phosphate are shifted as far as
possible towards the end of system I. (ii) Explicit conditions for the optimal
location of the ATP-consuming reactions are presented. The results are discussed
in the context of characteristic times as well as in terms of enzyme kinetic
parameters. (iii) For two sets of characteristic times the resulting
stoichiometries and their corresponding steady-state fluxes are investigated in
detail. One of these stoichiometries shows a close correspondence to contemporary
standard glycolysis. (iv) It is shown that most possible pathways result in a
very low steady-state flux, that is, the optimal stoichiometry is characterized
by a significant selective advantage. (v) The standard free energy profile of a
pathway with an optimal stoichiometry is discussed. It differs significantly from
the free energy profiles of nonoptimized pathways.
PMID- 9652954
TI - International League against Epilepsy (British Branch) annual scientific meeting.
Oxford, October 1997. Abstracts.
PMID- 9652955
TI - [On the 80th birthday of Oleksandr Oleksiiovych Shalimov].
PMID- 9652956
TI - [Biochemistry of presenilin 1].
AB - The majority of cases of early-onset familial Alzheimer disease are caused by
mutations in the recently identified presenilin 1 (PS 1) gene, located on
chromosome 14. PS1, a 467 amino acid protein, is predicted to be an integral
membrane protein containing seven putative transmembrane domains and a large
hydrophilic loop between the sixth and seventh membrane-spanning domain. We
produced 7 monoclonal antibodies that react with 3 non-overlapping epitopes on
the N-terminal hydrophilic tail of PS1. The monoclonal antibodies can detect the
full size PS1 at M(r) 47,000 (47K) and a more abundant M(r) 28,000 (28K) product
in membrane from human brain and human cell lines. We examined the sub-cellular
localization by using these antibodies. Immuno-electronmicroscopic and
biochemical analysis indicated that PS1 is localized on cellular membrane
(plasma, endoplasmic reticulum, and perinuclear) in COS-7 cells overexpressing
PS1. Interestingly, the PS1 immunoreactivity in the plasma membrane was
concentrated in the regions with cell-cell contact. This observation suggests a
possible role of PS1 on the cell membrane as a cell adhesion molecule. To
determine the protease cleaving the full length PS1 to two fragments, we treated
cells with various protease inhibitors. Only proteasome inhibitor affected the
PS1 processing, indicating that proteasome is a candidate protease for PS1
proteolytic cleavage. PC12 cells transiently transfected with PS1 constructs
containing different Alzheimer mutations fail to generate the 28K degradation
product in contrast to PC12 cells transfected with wild type PS1. Our results
indicate that missense mutations in this form of familial Alzheimer disease may
act via a mechanism of impaired proteolytic processing of PS1.
PMID- 9652957
TI - Leadership in child advocacy.
PMID- 9652958
TI - Implant ID cards.
PMID- 9652959
TI - An infection control procedure that is the patient's responsibility.
PMID- 9652960
TI - Society of Oral Physiology, Store Kro Group, 20th biennial meeting. Lattrop, the
Netherlands, 22-25 May 1997. Abstracts.
PMID- 9652961
TI - Acetaminophen: a clarification.
PMID- 9652962
TI - Which Ca2+ channels control cardiac E-C coupling?
PMID- 9652963
TI - [Molecular Biology 30th Anniversary Conference. Moscow, December 17-19, 1997.
Abstracts].
PMID- 9652964
TI - More on school health and the pediatrician.
PMID- 9652965
TI - More on the role of the school in ADHD.
PMID- 9652966
TI - More on the role of the school in ADHD.
PMID- 9652967
TI - Personal digital assistants. Another step toward ubiquitous computing.
PMID- 9652968
TI - Effects of smoking on the periodontium.
PMID- 9652969
TI - Evidence that elevated plasma corticosterone levels are the cause of reduced
hypothalamic corticotrophin-releasing hormone gene expression in diabetes.
AB - Uncontrolled diabetes mellitus causes both a sustained activation of the
hypothalamic-pituitary-adrenal (HPA) axis and reduced expression of
corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular
nucleus (PVN). To investigate the role of glucocorticoids in the regulation of
CRH mRNA expression in the PVN of diabetic rats, we studied surgically
adrenalectomized (ADX) and sham-operated male Sprague-Dawley rats 4 days after
i.v. injection of streptozotocin (STZ; 65 mg/kg i.v.) or vehicle. Among sham
operated animals, AM plasma corticosterone levels were significantly increased in
diabetic as compared to nondiabetic animals (1.46+/-0.54 vs. 0.22+/-0.05
microg/dl; P <0.05), and were positively correlated to both plasma ACTH levels (r
= 0.74; P = 0.015) and adrenal gland weight (r = 0.70; P = 0.025). In contrast,
CRH mRNA levels measured in the PVN by in situ hybridization were inversely
related to the plasma corticosterone level (r = -0.68; P = 0.045). In a second
experiment, both diabetic and nondiabetic ADX rats received a continuous
subcutaneous infusion of either corticosterone at one of two doses or its vehicle
for 4 days. Among vehicle-treated ADX animals, STZ diabetes raised hypothalamic
CRH mRNA levels, in contrast to the tendency for diabetes to lower CRH mRNA in
intact rats in the first experiment. Corticosterone administration lowered CRH
mRNA comparably in both diabetic and nondiabetic ADX rats. In contrast, diabetes
reduced arginine vasopressin (AVP) mRNA levels in the PVN of ADX rats and blunted
the inhibitory effect of glucocorticoids on AVP mRNA levels in this setting. We
conclude (1) glucocorticoids are necessary for the effect of diabetes to reduce
hypothalamic CRH gene expression, since diabetes causes a paradoxical increase in
CRH mRNA levels in adrenalectomized animals; (2) glucocorticoid inhibition of
hypothalamic CRH gene expression is intact in diabetic rats; and (3) the
activation of the HPA axis by diabetes is associated with a proportionate
decrease in PVN CRH gene expression. These findings support a model in which
hypothalamic factors additional to CRH activate the HPA axis in uncontrolled
diabetes, and inhibit CRH gene expression indirectly by negative glucocorticoid
feedback.
PMID- 9652970
TI - Pharmacological characterization and selectivity of the NPY antagonist GR231118
(1229U91) for different NPY receptors.
AB - Neuropeptide Y (NPY) is widely distributed throughout the central and peripheral
nervous system and exerts a wide range of physiological responses by activating
specific receptors. In this study we have characterized the potency of the high
affinity peptide dimer antagonist, GR231118, to displace radiolabeled NPY/PYY
from different tissues and cell lines expressing Y1 or Y2 receptors and from CHO
cells stably transfected with human cDNA encoding for Y1, Y2 and Y4 receptors.
GR231118 displays high affinity for Y1 and Y4 receptors, equal or better than
that of NPY itself, while its activity is several fold weaker for Y2 receptors.
Displacement of radiolabeled PYY from rat hypothalamic membranes by GR231118,
reveals the existence of high and low affinity binding sites which may be equated
to Y1 and Y2 receptors respectively suggesting that the compound maybe used as a
tool to dissect central NPY receptors.
PMID- 9652971
TI - Increased receptor sensitivity to neuropeptide Y in the hypothalamus may underlie
transient hyperphagia and body weight gain.
AB - Disruption of neural signaling by microinjection of a neurotoxin, colchicine
(COL), in the ventromedial hypothalamus (VMH) of rats results in rapid and
transient hyperphagia and body weight gain. Since neuropeptide Y (NPY) is a
potent hypothalamic orexigenic signal and continuous NPY receptor activation by
intracerebroventricular (icv) NPY infusion results in hyperphagia and obesity, we
tested the hypothesis that altered NPYergic signaling may underlie the transient
hyperphagia in COL-injected rats. Immediately following COL (4 microg)
microinjections in the ventromedial nucleus (VMN) rats displayed hyperphagia both
during the lights-on and lights-off periods. Concomitant with hyperphagia,
preproNPY mRNA levels in the arcuate nucleus and NPY levels in the
paraventricular nucleus decreased in a time-dependent manner. However, food
intake in response to intracerebroventricular injections of NPY (29, 117 and 470
pmole) was significantly higher in COL-injected rats and the latency to
initiation of feeding was markedly reduced as compared to controls. The smallest
dose of NPY which was virtually ineffective in control rats, evoked near maximal
intake in COL-injected rats. This enhanced response lasted for only 4 days
paralleling the transient hyperphagia. The NPY Y1 receptor antagonist 1229U91 (5
or 30 microg/rat, icv) significantly suppressed feeding in COL-treated rats
thereby indicating that hyperphagia in these rats was dependent upon endogenous
NPY. Overall, these studies demonstrate that not only high levels, but low levels
of NPY may also result in hyperphagia and increased body weight and this
hyperphagia may be attributed to the rapid development of NPY Y1 receptor
hypersensitivity.
PMID- 9652972
TI - Endogenous CCK inhibits colonic contractions in unrestrained conscious rats.
AB - As cholecystokinin octapeptide (CCK-OP) and feeding have been reported to relax
the circular muscle contractions of the proximal colon in unrestrained conscious
rats under fasting conditions, the, action of cholecystokinin, released after
duodenal infusion of a low residual diet of clinimeal, was studied on the motor
activity of the proximal colon in unrestrained conscious rats. We used an
implantable telemetry system with a miniature strain gauge force transducer
introduced into the rat proximal colon. By using a specific radioimmunoassay
system for CCK, plasma levels of CCK before and after duodenal infusion of
clinimeal (0.5, 1.0, 2.0 ml) were determined at 0, 5, 10, 20, 30, 60 min in the
portal blood. The clinimeal infusion caused a significant increase in CCK levels
of the portal plasma during 5 and 30 min. This increase was in a dose-dependent
manner. In accordance with this increase in plasma CCK, the motor activity of the
proximal circular muscle was suppressed significantly. A bolus injection of the
CCK A receptor antagonist, loxiglumide, CR 1505 (0.1, 0.5 and 1.0 mg/kg ip),
prior to clinimeal blocked the inhibitory action of CCK on the motor activity in
a concentration-dependent manner. These data suggest that endogenous CCK released
by a residual diet is involved in the mechanism of inhibition of motor activity
in the proximal colon.
PMID- 9652973
TI - Angiotensin receptors and norepinephrine neuromodulation: implications of
functional coupling.
AB - The objective of this review is to examine the role of neuronal angiotensin II
(Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have
been identified in cardiovascularly relevant areas of the brain: the AT1 and the
AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1
and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE)
neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE
neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE
release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor
mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and
ultimately leads to an increase in NE transporter, tyrosine hydroxylase and
dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a
Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+
channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors
will be discussed.
PMID- 9652974
TI - PACAP stimulates pancreatic exocrine secretion via the vagal cholinergic nerves
in sheep.
AB - The present study evaluates the possible role of the vagus nerves in mediating
the stimulatory effect of PACAP-27, PACAP-38 and VIP on the exocrine pancreas,
especially on enzyme secretion which is atropine sensitive in sheep. The animals
were equipped with two cannulae into the common bile duct, a duodenal cannula,
and a ruminal cannula under anesthesia. The bilateral cervical vagus nerves were
coiled with a cooling device. In conscious animals, the peptides were infused
intravenously for 10 min at 10 pmol kg(-1)min(-1) in phase II of the duodenal
migrating motor complexes and the same peptide infusion was repeated in the
reversible cooling blockade of the vagus nerves. Increment in fluid secretion was
not significantly altered by the vagal blockade in all the peptide infusions,
while increment in bicarbonate ion by only PACAP-27 was inhibited by the vagal
blockade. Increments in protein and amylase output decreased significantly to
32.0+/-5.0 and 23.2+/-2.6% in PACAP27, and to 26.1+/-7.7 and 20.8+/-6.4% in PACAP
38 in the vagal blockade, but the increments by VIP did not decrease. These
results demonstrate that circulating PACAP stimulates pancreatic enzyme secretion
via the vagal cholinergic preganglionic neurons in sheep, suggesting the central
action of PACAP.
PMID- 9652975
TI - Renal aminopeptidase activities in animal models of hypertension.
AB - Aminopeptidase activity (AP) has been implicated in the metabolism of renal and
circulating vasoactive peptides. This activity is involved in the pathogenia of
hypertension, essentially in spontaneously hypertensive rats. However, no other
animal models, which develop hypertension by other different ways, have been used
to study the possible role of aminopeptidase activity. To investigate the role of
this activity in the pathogenesis of hypertension, angiotensinase A activity
(glutamyl-AP and aspartyl-AP), aminopeptidase M activity (alanyl-AP),
aminopeptidase B activity (arginyl-AP), pyroglutamyl-AP, and cystinyl-AP were
measured in the serum and kidney of two experimental animal models of
renovascular hypertension: Goldblatt two-kidney one clip (G2K-1C) and low renal
mass rats (LRM). No differences were found in serum levels of AP in LRM or G2K-1C
in comparison with their respective controls. In LRM rats there was a significant
decrease in membrane-bound angiotensinase A (glutamyl-AP), arginyl-AP and alanyl
AP activities. In G2K-1C rats there was a significant decrease in soluble and
membrane-bound angiotensinase A activity (aspartyl-AP). Our results suggest that
AP activities play a role in the regulation of renal vasoactive peptides, and
respond differently depending on the cause of hypertension.
PMID- 9652976
TI - Prolonged pheromonotropic activity of pseudopeptide mimics of insect pyrokinin
neuropeptides after topical application or injection into a moth.
AB - Amphiphilic pseudopeptide analogs of Phe-Thr-Pro-Arg-Leu-NH2, representing the
active C-terminal core pentapeptide of the pyrokinin class of insect
neuropeptides, were synthesized by replacement of phenylalanine with
hydrocinnamic acid (Hca-Thr-Pro-Arg-Leu-NH2), or addition of 1-pyrenebutyric acid
(Pba-Phe-Thr-Pro-Arg-Leu-NH2) or 9-fluoreneacetic acid (Fla-Phe-Thr-Pro-Arg-Leu
NH2). The pseudopeptides were found to stimulate sex pheromone biosynthesis when
injected into females of the moth Heliothis virescens. Optimal pheromonotropic
responses were obtained by injection of 0.25 pmol of Hca-Thr-Pro-Arg-Leu-NH2, 2.5
pmol of Pba-Thr-Pro-Arg-Leu-NH2 and 0.5 pmol of Fla-Thr-Pro-Arg-Leu-NH2. Topical
application of each of the pseudopeptides in water to the cuticle of moths
stimulated significant production of pheromone at a dose of 50 pmol with optimal
stimulation occurring when 500 pmol were applied. The parent peptide, Phe-Thr-Pro
Arg-Leu-NH2, failed to stimulate significant production of pheromone when applied
topically at a dose as high as 2000 pmol. Temporal studies indicated that Hca-Thr
Pro-Arg-Leu-NH2 stimulated significant production of pheromone for only 4 h after
application where as continuous pheromone production for 18 h was observed when
either Pba-Phe-Thr-Pro-Arg-Leu-NH2 or Fla-Phe-Thr-Pro-Arg-Leu-NH2 were applied to
the abdomen. The results show that modification of the C-terminal active core of
the insect pyrokinins, by addition of hydrophobic moieties, can result in
production of pseudopeptides which effectively penetrate the insect cuticle and
have prolonged physiological effects making them favorable candidates for use in
development of alternative strategies for pest insect control.
PMID- 9652977
TI - Neutrophil extracted lipocortin inhibits corticotropin secretion in the AtT-20
D16:16 clonal mouse pituitary cell line. Lipocortin inhibition of ACTH release in
vitro.
AB - The mechanism of short-term glucocorticoid (GC) inhibition of the hypothalamic
pituitary-adrenal axis is not well understood. The direct anti-inflammatory
activities of lipocortins (LCs) have suggested a role for them as extra- and
intracellular mediators of the biological effects of GCs. It has been reported
that recombinant human (rh) LC1 inhibits corticotropin (ACTH) release from
pituitary tissue in vitro but not from AtT-20 D16:16 corticotrophs. Using the
same cell line we have tested whether other exogenous rhLCs or native LC
extracted from polymorphonucleate neutrophils (neLC), likely LC1, have an effect
on ACTH secretion. It is shown that: (1) basal release was not affected by a
short-term incubation with neLC; (2) secretion induced by corticotropin-releasing
factor (CRF) and other secretagogues (phorbol ester, potassium ion or calcium
ionophore) was inhibited by neLC; (3) GC inhibition of CRF-stimulated release was
reverted by a monoclonal anti-neLC antibody; (4) rhLC2, rhLC5 and the fragment
212-234 of rhLC5 were without effect. Thus, only neLC is effective on AtT-20
D16:16 cells, suggesting for this annexin a role in the early phase GC inhibition
of ACTH secretion.
PMID- 9652978
TI - Urinary excretion of epidermal growth factor and Tamm-Horsfall protein in three
rat models with increased renal excretion of urine.
AB - Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are synthesized in
the kidneys by the distal tubular cells and excreted into urine. The urinary
excretion of these peptides has been suggested as a potential index for distal
tubular function. The urinary excretion rates of EGF and THP were examined in
three groups of rats with increased renal excretion of urine: uninephrectomy, non
osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples
were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled
in uninephrectomy when compared to controls. There was a seven-fold increase in
urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria,
as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all
affected the urinary excretion of EGF and THP differently. The EGF excretion in
uninephrectomized rats was 60-80% of that of the controls, whereas THP excretion
was unchanged, indicating that EGF excretion varied with renal tissue mass. Non
osmotic polyuria caused a five-fold increase in THP excretion but no change in
EGF excretion. THP excretion in the diabetic rats was increased three-fold after
21 days when compared to controls, whereas EGF excretion was decreased when
expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP
were colocalized in the thick ascending limbs of Henle's loops and distal tubules
in all five groups of rats. In conclusion, the EGF excretion appears to follow
renal tissue mass and seems independent of urinary volume, whereas THP excretion
is dependent mainly on urinary volume. This has implications for the use of EGF
and/or THP excretion rates as an indicator for distal tubular function.
PMID- 9652979
TI - Functional impairment of the individual rat stomach ECL cell in response to
sustained hypergastrinemia.
AB - ECL cells in the oxyntic mucosa secrete histamine and pancreastatin in response
to gastrin. The present study examined gastrin-evoked ECL-cell responses over a
10-week time span in terms of individual ECL cells and unit ECL cell volume. Rats
were treated with omeprazole (400 micromol/kg per day orally). The concentrations
of gastrin and pancreastatin in serum and of histamine and pancreastatin in the
oxyntic mucosa were measured as was the activity of the oxyntic mucosal histidine
decarboxylase (HDC). The ECL cells were visualized by immunostaining of histamine
and examined by electron microscopy. The total ECL cell number and volume, and
the mean ECL cell diameter and volume were determined. The HDC, chromogranin A
(CGA) and cholecystokinin-B (CCK-B) receptor mRNA concentrations were determined.
In terms of individual ECL cells and unit ECL cell volume, the serum
pancreastatin concentration, the oxyntic mucosal histamine content, HDC activity,
and HDC, CGA and CCK-B receptor mRNA contents increased slowly at first and then
leveled off or started to decline after 2 weeks. After 10 weeks all ECL-cell
parameters (expressed per unit ECL cell volume) were back to or approaching the
starting value. In conclusion, sustained hypergastrinemia first activates each
individual ECL cell (with a peak after 1-2 weeks) and then causes gradual
functional impairment, the activity returning towards the pre-stimulation level.
PMID- 9652980
TI - CGRP and substance P in intraepithelial neuronal structures of the human upper
respiratory system.
AB - The distribution of intraepithelial nerve fibres and neuroendocrine cells within
the surface and glandular epithelium of human nasal mucosa and larynx was
examined using immunohistochemical techniques. Neuronal structures were
immunostained for the general neuroendocrine marker protein gene-product (PGP)
9.5, and the two neuropeptides substance P (SP) and calcitonin gene-related
peptide (CGRP) using immunofluorescence and streptavidin-biotin-peroxidase
complex (S-ABC) methods. Intraepithelial nerve fibres with free nerve endings
contained PGP 9.5 and were found within the respiratory surface epithelium of the
nasal mucosa and the squamous epithelium of the larynx. A subpopulation of these
nerve fibres showed positive immunoreactivties with antibodies against SP and
CGRP. Nerve fibres within the ductal epithelium of subepithelial excretory ducts
passing the basal membrane and reaching the luminal part were detected. These
nerve fibres showed CGRP-like immunoreactivity but not for SP. A dense network of
nerve fibres within the squamous surface epithelium was detected in the
subglottic and epiglottic region containing CGRP and SP in a small subpopulation
of nerve fibres. Single intraepithelial taste buds in the epiglottic region and
neuroendocrine cells within the subglottic epithelium expressed PGP 9.5.
PMID- 9652981
TI - Effects of OPC-21268, a vasopressin V1-receptor antagonist, on expression of
growth factors from glomeruli in spontaneously hypertensive rats.
AB - To assess the chronic in vivo effects of OPC-21268, a vasopressin-V1 receptor
antagonist, on renal injury, we investigated the mRNA expressions of platelet
derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta1 and
proliferating cell nuclear antigen (PCNA) in the glomeruli of spontaneously
hypertensive rats (SHR) treated with OPC-21268 for 3 weeks. SHR aged 10 weeks
were given 2% NaCl in drinking water for 3 weeks. The OPC group was fed a 0.5%
OPC-21268-containing diet for 3 weeks and the control group was given a normal
diet. There were no significant changes in the time course of systolic blood
pressure, heart rate, urine volume, or urinary sodium, protein and N-acetyl-beta
glucosaminidase (NAG) excretion between the two groups. Serum electrolytes,
protein and creatinine levels also did not differ between the groups. The mRNA
expressions of PDGF B-chain, TGF-beta1 and PCNA in the glomerulus were examined
using reverse transcriptase-polymerase chain reaction (RT-PCR) methods. The mRNA
expressions of PDGF B-chain and PCNA among these were significantly suppressed in
the OPC group. No significant differences in renal histology including the organ
weights were found between the two groups; however, the glomerular size tended to
be enlarged in the OPC group. These findings suggest that chronic V1-receptor
blockade directly inhibits the glomerular proliferative injury of salt-loaded SHR
at the established hypertension stage.
PMID- 9652982
TI - Mutational analysis of the angiotensin II type 2 receptor: contribution of
conserved extracellular amino acids.
AB - While much work has been done examining the ligand-binding characteristics of the
AT1 receptor, very little attention has been focused on the AT2 receptor. Both
receptors bind angiotensin II (AngII) with identical affinities, but share only
34% homology. Although it is tempting to assume that conserved residues between
the two subtypes are responsible for the binding of AngII, there is little data
to support this view. To determine the commonalities in ligand binding of the AT1
and AT2 receptors, we have chosen several conserved extracellular amino acids
which have been shown to be important in AngII binding [1,2] to the AT1 receptor
for mutational studies of the AT2 receptor. Specifically, we have mutated
tyrosine108 in extracellular loop 1 (ECL1), arginine182 in ECL2, and aspartate297
in ECL3 of the AT2 receptor in order to determine their contribution to AngII
binding. In the AT2 receptor, mutation of tyrosine108 to an alanine resulted in a
receptor with wild-type binding for AngII, while mutation of either arginine182
or aspartate297 drastically impaired AngII binding ( > 100 nM). These results
demonstrate both similarities as well as clear differences between receptor
subtypes in the contributions to AngII binding of several conserved extracellular
amino acid residues.
PMID- 9652983
TI - Proceedings of the 8th International Symposium of Nephrology. Montecatini Terme,
Italy, October 7-9, 1996.
PMID- 9652984
TI - Frequency of HIV testing and diagnosis in a KwaZulu-Natal regional hospital.
PMID- 9652985
TI - Proceedings, white pages, and recommendations from the consensus conference on
developing practice guidelines for institutionalized older dental patients.
PMID- 9652986
TI - [A new generation of anti-allergic preparations: an expansion of the therapeutic
possibilities].
PMID- 9652987
TI - [Transurethral endoscopic electrovaporization in the treatment of patients with
benign prostatic hyperplasia].
PMID- 9652988
TI - [Georgii Semenovich Grebenshchikov (on the centenary of his birth)].
PMID- 9652989
TI - [Schoenlein-Henoch purpura with intestinal involvement].
PMID- 9652990
TI - [Transmission of hepatitis C in gastrointestinal endoscopy--media sensationalism
or a clinically relevant problem?].
PMID- 9652991
TI - Miss-'n-mix and mimics. Emergency drugs.
PMID- 9652992
TI - Report of the NIH Panel To Define Principles of Therapy of HIV Infection.
AB - Recent research advances have afforded substantially improved understanding of
the biology of HIV infection and the pathogenesis of AIDS. With the advent of
sensitive tools for monitoring HIV replication in infected persons, the risk for
disease progression and death can be assessed accurately and the efficacy of anti
HIV therapies can be determined directly. Furthermore, when used appropriately,
combinations of newly available, potent antiviral therapies can effect prolonged
suppression of detectable levels of HIV replication and circumvent the inherent
tendency of HIV to generate drug-resistant viral variants. However, as
antiretroviral therapy for HIV infection has become increasingly effective, it
has also become increasingly complex. Familiarity with recent research advances
is needed to ensure that newly available therapies are used in ways that most
effectively improve the health and prolong the lives of HIV-infected persons. To
enable practitioners and HIV-infected persons to best use rapidly accumulating
new information about HIV disease pathogenesis and treatment, the Office of AIDS
Research of the National Institutes of Health (NIH) sponsored the NIH Panel To
Define Principles of Therapy of HIV Infection. This Panel was asked to define
essential scientific principles that should be used to guide the most effective
use of antiretroviral therapies and viral load testing in clinical practice. On
the basis of detailed consideration of the most current data, the Panel
delineated 11 principles that address issues of fundamental importance for the
treatment of HIV infection. These principles provide the scientific basis for the
specific treatment recommendations made by the Panel on Clinical Practices for
the Treatment of HIV Infection sponsored by the Department of Health and Human
Services and the Henry J. Kaiser Family Foundation. The reports of both of these
panels are provided in this supplement. Together, they summarize new data and
provide both the scientific basis and specific guidelines for the treatment of
HIV-infected persons. This information will be of interest to health care
providers, HIV-infected persons, HIV and AIDS educators, public health educators,
public health authorities, and all organizations that fund medical care of HIV
infected persons.
PMID- 9652993
TI - Guidelines for the use of antiretroviral agents in HIV-infected adults and
adolescents. Department of Health and Human Services and the Henry J. Kaiser
Family Foundation.
PMID- 9652994
TI - The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate
in postmenopausal women with moderate osteoporosis. A randomized, controlled
trial.
AB - BACKGROUND: Fluoride is effective in increasing trabecular bone mineral density
(BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its
effect on BMD at cortical sites are controversial. OBJECTIVE: To study the effect
of low-dose fluoride (sodium monofluorophosphate [MFP]) plus a calcium supplement
over 4 years on vertebral fractures and BMD at the lumbar spine and total hip in
postmenopausal women with moderately low BMD of the spine. DESIGN: Randomized,
double-blind, controlled clinical trial. SETTING: Outpatient clinic for
osteoporosis at a university medical center. PATIENTS: 200 postmenopausal women
with osteoporosis (according to the World Health Organization definition) and a T
score less than -2.5 for BMD of the spine. INTERVENTION: Women were randomly
assigned (100 patients per group) to continuous daily treatment for 4 years with
1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium (as calcium
carbonate) or 2) calcium only. MEASUREMENTS: Lateral spine radiographs were taken
at enrollment and at each year of follow-up for detection of new vertebral
fractures (defined as a reduction > or =20% and > or =4 mm from baseline in any
of the heights of a vertebral body). Nonvertebral fractures were also recorded.
All analyses were done with the intention-to-treat approach. RESULTS: Radiologic
follow-up was possible for 164 of 200 patients (82%). The rate of new vertebral
fractures during the 4 years of the study was lower in the MFP-plus-calcium group
(2 of 84 patients; 2.4% [95% CI, 0.3% to 8.3%]) than in the calcium-only group (8
of 80 patients; 10% [CI, 4.4% to 18.8%]). The difference between the groups was
7.6 percentage points (CI, 0.3 to 15 percentage points) (P = 0.05). A moderate
but progressive increase in BMD of the spine (10.0% +/- 1.5% at 4 years) was
found for MFP plus calcium compared with calcium only (P < 0.001), whereas the
more modest increase in BMD of the total hip seen with MFP plus calcium (1.8% +/-
0.6%) did not differ from the increase seen with calcium only. CONCLUSIONS: Low
dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can
decrease vertebral fracture rates compared with calcium alone in patients with
mild to moderate osteoporosis.
PMID- 9652995
TI - Effects of androgen administration in men with the AIDS wasting syndrome. A
randomized, double-blind, placebo-controlled trial.
AB - BACKGROUND: Development of successful anabolic strategies to reverse the loss of
lean body mass is of critical importance to increase survival in men with the
AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state
characterized by loss of testosterone, occurs in more than half of all men with
advanced HIV disease. It is unknown whether testosterone deficiency contributes
to the profound catabolic state and loss of lean body mass associated with the
AIDS wasting syndrome. OBJECTIVE: To investigate the effects of physiologic
testosterone administration on body composition, exercise functional capacity,
and quality of life in androgen-deficient men with the AIDS wasting syndrome.
DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University
medical center. PATIENTS: 51 HIV-positive men (age 42 +/- 8 years) with wasting
(body weight < 90% of ideal body weight or weight loss > 10% of baseline weight)
and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49
years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]). INTERVENTION: Patients were
randomly assigned to receive testosterone enanthate, 300 mg, or placebo
intramuscularly every 3 weeks for 6 months. MEASUREMENTS: Change in fat-free mass
was the primary end point. Secondary clinical end points were weight, lean body
mass, muscle mass, exercise functional capacity, and change in perceived quality
of life. Virologic variables were assessed by CD4 count and viral load. RESULTS:
Compared with patients who received placebo, testosterone-treated patients gained
fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg;
P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in
weight, fat mass, total-body water content, and exercise functional capacity did
not significantly differ between the groups. Patients who received testosterone
reported benefit from the treatment (P = 0.036), feeling better (P = 0.033),
improved quality of life (P = 0.040), and improved appearance (P = 0.021).
Testosterone was well tolerated in all patients. CONCLUSIONS: Physiologic
testosterone administration increases lean body mass and improves quality of life
among androgen-deficient men with the AIDS wasting syndrome.
PMID- 9652996
TI - Surgery for recurrent colon cancer: strategies for identifying resectable
recurrence and success rates after resection. Eastern Cooperative Oncology Group,
the North Central Cancer Treatment Group, and the Southwest Oncology Group.
AB - BACKGROUND: Follow-up testing after surgery for colon cancer is recommended
principally to identify resectable recurrences, but data on the efficacy of,
outcomes of, and optimal strategies for this testing are limited. OBJECTIVES: To
determine the relation between follow-up tests and salvage surgery, assess
outcomes, and document surgical mortality. DESIGN: Retrospective cohort study.
SETTING: A North American multi-institutional trial comparing postoperative
chemotherapy plus follow-up with follow-up alone. PATIENTS: 1247 patients with
resected stage II and stage III colon cancer. INTERVENTION: The protocol mandated
follow-up testing that could be supplemented at the discretion of treating
physicians. Indications of recurrent disease were documented. MEASUREMENTS:
Recurrence, resectable recurrence, surgical mortality, and survival were studied.
RESULTS: 548 patients had recurrence of colon cancer. Salvage surgery was
attempted in 222 patients (41%). In 109 patients (20%), curative-intent surgery
was done for hepatic recurrence (28 patients), pulmonary metastasis (20
patients), local recurrence (24 patients), or recurrence at other sites (37
patients). Most curative-intent surgical procedures were motivated by follow-up
testing (36 patients), elevated carcinoembryonic antigen level (41 patients), or
symptoms (27 patients). The median follow-up time after curative-intent surgery
exceeded 5 years; the estimated 5-year disease-free survival rate was 23%. A
solitary lesion was a favorable prognostic factor. The surgical mortality rate
was 2%. Curative-intent resections were done in 15 patients with second primary
colorectal cancer; 12 of these patients have survived disease-free. CONCLUSIONS:
Second operations for colon cancer that are triggered by follow-up testing or
symptoms are common and can result in long-term disease-free survival.
PMID- 9652997
TI - Two cases of severe clinical and histologic hepatotoxicity associated with
troglitazone.
PMID- 9652998
TI - Troglitazone-induced hepatic failure leading to liver transplantation. A case
report.
AB - BACKGROUND: Troglitazone is a new drug for the treatment of type 2 diabetes.
Although mild liver injury occurred in 1.9% of participants in controlled trials,
the U.S. Food and Drug Administration has received reports of five postmarketing
cases of severe liver disease that resulted in death or liver transplantation.
OBJECTIVE: To report the clinical and histopathologic characteristics of a
patient with troglitazone-associated severe liver injury leading to
transplantation. DESIGN: Case report. SETTING: Two university hospitals. PATIENT:
A 55-year-old woman taking troglitazone, 400 mg/d, and insulin, 120 U/d.
INTERVENTION: Discontinuation of troglitazone therapy, pretransplantation liver
biopsy, and liver transplantation. RESULTS: Early nonspecific symptoms were
attributed to other causes and were not evaluated. After the patient had used
troglitazone for 3.5 months, massive loss of liver parenchyma and symptoms of
liver failure developed, necessitating liver transplantation. CONCLUSION:
Troglitazone may cause subfulminant liver failure.
PMID- 9652999
TI - Methods for evaluating the clinical competence of residents in internal medicine:
a review.
AB - This paper reviews methods commonly used to assess the clinical competence of
residents in internal medicine, including the In-Training Examination, medical
record audits, rating scales, clinical evaluation exercises, and the use of
standardized patients. Studies were identified through a MEDLINE search (1966 to
present) and from the bibliographies of relevant articles and were selected for
inclusion according to consensus between the authors. Whenever possible, original
studies were chosen over reviews and editorials. No single assessment method can
successfully evaluate the clinical competence of residents in internal medicine,
and educators need to be cognizant of the most appropriate applications and the
advantages and disadvantages of the available evaluation tools. A combination of
assessment tools provides the best opportunity to evaluate and educate physicians
in-training.
PMID- 9653000
TI - Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease.
Part 2: Inflammatory bowel disease, systemic vasculitis, and therapeutic
toxicity.
AB - When cytotoxic agents were introduced, their ability to disrupt nucleic acid and
protein synthesis led to their effective use for the treatment of neoplastic
disease. During the course of this use, however, it became apparent that these
agents also suppress the immune system. This usually unwelcome effect was
subsequently studied and beneficially directed toward the treatment of non
neoplastic diseases in which autoimmune mechanisms were considered important to
pathogenesis. As a result of these investigations, cytotoxic agents and, more
recently, cyclosporine have emerged to become an important part of the
therapeutic regimen for many autoimmune diseases. Nonetheless, these medications
may still cause treatment-induced illness or even death. It is therefore
particularly important to weigh the benefits and risks of cytotoxic therapy when
treating a non-neoplastic disease. This two-part Clinical Staff Conference
reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in
selected autoimmune diseases. In part 2, we focus on the role of these agents in
treating inflammatory bowel disease and systemic vasculitis and review the toxic
effects of these agents.
PMID- 9653001
TI - Clinician-educators in academic medical centers: a two-part challenge.
AB - As academic medical centers increasingly deliver care in primary care settings, a
new category of faculty-clinician-educators-has emerged. Although the shift of
education and patient care to outpatient settings makes the expanded role of
clinician-educators necessary, it also presents challenges to clinician-educators
themselves and to the institutions for which they work. This article examines
these contemporary challenges (including financial constraints, undefined
processes of promotion, and limited opportunities for professional development)
and suggests strategies for meeting them. The number of clinician-educators
joining the ranks of medical school faculties will probably continue to increase.
As clinician-educators seek to provide the highest-quality education and patient
care in the new medical marketplace, their success will be critical to the
viability of the academic centers of the future.
PMID- 9653002
TI - Complementary care: when is it appropriate? Who will provide it?
PMID- 9653003
TI - The escape.
PMID- 9653004
TI - Critical pathway for chest pain.
PMID- 9653005
TI - Body mass and hypertension in women.
PMID- 9653006
TI - Bronchiolitis obliterans-organizing pneumonia caused by ticlopidine.
PMID- 9653007
TI - Reversible dysgeusia attributed to losartan.
PMID- 9653008
TI - Acute intravascular hemolysis after pollen ingestion.
PMID- 9653009
TI - Electronic cancer Munchausen syndrome.
PMID- 9653010
TI - New cardiovascular training track: reinventing the wheel?
PMID- 9653011
TI - Fighting the war on breast cancer: debates over early detection, 1945 to the
present.
PMID- 9653012
TI - Congruence between decisions to initiate chiropractic spinal manipulation for low
back pain and appropriateness criteria in North America.
AB - BACKGROUND: Recent U.S. practice guidelines recommend spinal manipulation for
some patients with low back pain. If followed, these guidelines are likely to
increase the number of persons referred for chiropractic care. Concerns have been
raised about the appropriate use of chiropractic care, but systematic data are
lacking. OBJECTIVE: To determine the appropriateness of chiropractors' decisions
to use spinal manipulation for patients with low back pain. DESIGN: Retrospective
review of chiropractic office records against preset criteria for appropriateness
that were developed from a systematic review of the literature and a nine-member
panel of chiropractic and medical specialists. Appropriateness criteria reflect
the expected balance between risk and benefit. SETTING: 131 of 185 (71%)
chiropractic offices randomly sampled from sites in the United States and Canada.
PATIENTS: 10 randomly selected records of patients presenting with low back pain
from each office (1310 patients total). MEASUREMENTS: Sociodemographic data on
patients and chiropractors; use of health care services by patients; assessment
of the decision to initiate spinal manipulation as appropriate, uncertain, or
inappropriate. RESULTS: Of the 1310 patients who sought chiropractic care for low
back pain, 1088 (83%) had spinal manipulation. For 859 of these patients (79%),
records contained data sufficient to determine whether care was congruent with
appropriateness criteria. Care was classified as appropriate in 46% of cases,
uncertain in 25% of cases, and inappropriate in 29% of cases. Patients who did
not undergo spinal manipulation were less likely to have a presentation judged
appropriate and were more likely to have a presentation judged inappropriate than
were patients who did undergo spinal manipulation (P = 0.01). CONCLUSIONS: The
proportion of chiropractic spinal manipulation judged to be congruent with
appropriateness criteria is similar to proportions previously described for
medical procedures; thus, the findings provide some reassurance about the
appropriate application of chiropractic care. However, more than one quarter of
patients were treated for indications that were judged inappropriate. The number
of inappropriate decisions to use chiropractic spinal manipulation should be
decreased.
PMID- 9653013
TI - 5th Congress of the International Society for Rotary Blood Pumps. Marseille,
France, September 10-12, 1997. Abstracts.
PMID- 9653014
TI - Candida onychomycosis in HIV infection.
AB - Primary nail invasion by Candida is uncommon and almost exclusively seen in
patients with an impaired immune function. The appearance of Candida
onychomycosis in an adult who is not under immunosuppressive treatment always
requires a laboratory evaluation of the immunologic function including HIV
assays. We report 2 cases of distal subungual onychomycosis due to Candida sp. in
HIV. In one of our patients, the diagnosis of Candida onychomycosis preceded the
diagnosis of advanced HIV infection. In both of our patients treatment with
systemic antifungals produced complete cure of Candida onychomycosis and the 1
year follow-up did not reveal any relapse of the onychomycosis.
PMID- 9653015
TI - Occurrence rates of HLA-DRB1, HLA-DQB1, and HLA-DPB1 alleles in patients
suffering from vitiligo.
AB - By investigating a group of 39 unrelated adults suffering from vitiligo it was
found that alleles HLA-DRB1*0701, -DQB1*0201, and -DPB1*1601 differed in their
frequencies in comparison to those observed in the healthy population. The allele
HLA-DRB1*0701 was found in 26.5% of patients compared to 14.2% in the healthy
group (p < 0,01, RR = 2.17). The allele HLA-DQB1*0201 was present in 33.8% of
patients compared to 21.2% (p < 0,025, RR = 1.89). The allele HLA-DPB1*1601 was
found in 6.41% of patients compared to 2.05% in the healthy group (p < 0.05, RR =
3.3). No other significant deviations in the frequencies of investigated alleles
were observed.
PMID- 9653016
TI - Characterisation of glucocorticoid receptors in peripheral blood leukocytes of
Carp, Cyprinus carpio L.
AB - Binding studies with [3H]cortisol revealed the presence of a single class of
cortisol-binding sites on carp peripheral blood leukocytes (PBL). These binding
sites showed high affinity (Kd of 3.8 nM) and low capacity (490 binding sites per
cell), indicative of receptor binding. Affinity for cortisone was 254-fold lower
than for cortisol. Affinity for the two synthetic glucocorticoids dexamethasone
and triamcinolone acetonide (TA) was 4- and 10-fold higher than for cortisol,
respectively. Further evidence for the GR character of the receptor came from
results showing that cortisol induced apoptosis, which could be blocked by the
glucocorticoid analogue RU486. A single meal of cortisol-containing food elevated
plasma cortisol concentrations and decreased GR density in PBL, as measured 3 h
later. The percentage of circulating B lymphocytes also decreased. Cortisol
induced redistribution of B lymphocytes from the blood, due to cortisol
treatment, may explain the decrease of GR numbers in PBL, although downregulation
of available GR remains possible.
PMID- 9653017
TI - Loss of glucose transporter-2 precedes insulin loss in the nonobese diabetic and
the low-dose streptozotocin mouse models: a comparative immunohistochemical study
by light and confocal microscopy.
AB - Glucose transporter-2 (glut2) is underexpressed in beta cells of several rodent
models of non-insulin-dependent diabetes mellitus (NIDDM). This may also be true
for rodent models of insulin-dependent diabetes mellitus (IDDM). The present
study examines two murine models of autoimmune IDDM, the nonobese diabetic (NOD)
and the low-dose streptozotocin (stz) murine models for changes in the expression
of glut2 by double-label light and confocal microscopy during various stages of
the disease. The spatial distribution of glut2 cells was also examined in
relation to insulin immunoreactive cells and the islet inflammatory cells during
these stages. In both the female NOD mouse and the female Swiss mouse without stz
treatment, glut2 colocalized with insulin in virtually all the beta cells. In the
NOD mouse, islets with moderate to advanced insulitis showed either an absence or
considerably reduce expression of glut2 in insulin-containing beta cells. Cells
with reduced glut2 expression were usually located adjacent to the region of
insulitis. At onset of diabetes, glut2 immunolabeling was reduced despite the
preservation of weak insulin immunoreactivity. In Swiss mice treated repeatedly
with stz, glut2 labeling began to decline in select Beta cells after the fourth
injection in approximately 50% of the islets, despite the lack of insulitis. At
this stage expression of glut2 fell in a small number of islets with evidence of
early macrophage infiltration. Loss of glut2 became more pronounced in
nondiabetic Swiss mice after the fifth injection. At this stage glut2 labeling in
the plasma membrane appeared diffuse and variable. At onset of stz-induced
diabetes, glut2 expression significantly fell, despite weak immunoreactivity for
insulin. This loss was associated with an enhanced influx of both macrophages and
T lymphocytes within the islets of diabetes mice. In both the NOD and the low
dose stz mouse models, loss of glut2 thus occurs from an early stage and precedes
hyperglycaemia. This loss may be mediated by immune and nonimmune mechanisms.
PMID- 9653018
TI - GLUT-4 Deficiency and severe peripheral resistance to insulin in the teleost fish
tilapia.
AB - Teleost fish, in general, are glucose intolerant; this trait has been attributed
to piscine islets secreting insulin primary in response to amino acid
secretogogues rather than glucose. However, pancreatic islet from the teleost
fish tilapia, when transplanted into diabetic nude mice, were glucose responsive
even though tilapia were severely glucose intolerant. This suggested a strong
peripheral resistance to the glucostatic effects of insulin. Using Western
blotting with polyclonal antibodies as well as Northern analysis for mRNA,
tilapia tissues were found to be devoid of GLUT-4, the insulin-sensitive glucose
transporter responsible for the hypoglycemic effect of insulin in mammals. The
absence of GLUT-4 in peripheral tissues may explain why tilapia, and possibly
other teleost fish, are severely glucose intolerant. This suggests that tilapia
islets have evolved along mammalian lines to be glucose sensitive while tilapia
peripheral tissue have diverged widely. Using the same methods, tilapia were
found to have a very limited tissue distribution of the insulin-independent
glucose transporter, GLUT-1, which is responsible for basal glucose transport in
mammalian cells. It is suggested that tilapia provide a naturally occurring GLUT
4 knockout model.
PMID- 9653019
TI - Immunological cross-reactivity between rainbow trout GTH I and GTH II and their
alpha and beta subunits: application to the development of specific
radioimmunoassays.
AB - Immunological cross-reactivities between rainbow trout GTH I and GTH II and their
alpha and beta have been studied using highly purified rainbow trout
gonadotropins and subunits and antibodies raised against beta subunits. From
these observations radioimmunoassays have been developed for rainbow trout GTH I
and GTH II. The GTH II RIA was highly specific and cross-reacted only with GTH II
and its beta 1 subunits, with beta 2 being less potent than beta 1 in competing
GTH II binding. There was no cross-reactivity with GTH I. Its sensitivity varied
between 0.1 and 0.2 ng/ml, allowing GTH II measurement early in the reproductive
cycle. Variations between and within assays were less than 10%. There was a lack
of specificity of GTH I RIA (44% cross-reactivity with GTH II, when using
labelled native GTH I). Reasons for this lack of sensitivity were studied. It
cannot be attributed to beta subunits (less than 1.2% cross-reactivity). However,
the cross-reactivity of alpha subunits was very important. This suggests that the
presence of free alpha subunits in the medium can be responsible for the lack of
specificity. Labelling native GTH I resulted in conformational change in
molecular weight and dissociation of the hormone into subunits, whereas
iodination did not induce GTH II dissociation. This dissociation can be avoided
by labelling the stable form of GTH I. Using this radio-tracer, the specificity
and the sensitivity of the assay were greatly improved (GTH II cross-reactivity
was decreased to 3.7, mean sensitivity 0.87 +/- 0.072 ng/ml). The sensitivity of
the assay diminished with ageing of labelled GTH I. The assay variation was 4.6%
within an assay and 9.8% between assays. The use of labelled beta GTH I still
increases the specificity (2.3% GTH II cross-reactivity), but with a 2.4-fold
loss of sensitivity. In both GTH I and GTH II RIA plasma and spiked plasma with
purified GTHs gave displacement curves parallel to standard. These assays were
used to study pituitary responsiveness to a GnRH analogue in female rainbow trout
prior to oocyte maturation. The effects of GnRH on GTH II secretion were
confirmed. The peptide did not significantly stimulate GTH I secretion.
PMID- 9653020
TI - GTH I and GTH II secretion profiles during the reproductive cycle in female
rainbow trout: relationship with pituitary responsiveness to GnRH-A stimulation.
AB - The recent purification of two gonadotropins, GTH I and GTH II, in teleost fish
and the development of their specific radioimmunoassays using antibodies directed
against their beta subunits have demonstrated that earlier assays for GTH II also
measured GTH I. Most of the results on the gonadotropic control of reproduction
in fish must thus be reinvestigated using specific assays for each gonadotropin.
The present investigation examines changes in blood plasma levels of GTH I and
GTH II during the annual reproductive cycle of rainbow trout in relation to the
ability of gonadotropin-releasing hormone (GnRH) to stimulate in vivo GTH I and
GTH II secretion, with focus on the periovulatory period. GTH I was detected from
immature to postovulatory stages, with a significant increase at the onset of
exogenous vitellogenesis, with GTH I levels rising from 7.83 +/- 3.37 to 16.87 +/
4.52 ng/ml. GTH II remained very low until the end of the vitellogenesis. For
both hormones, the most significant variations were measured during the
periovulatory period. GTH II levels peaked on the day of maturation, but the
increase was biphasic with a first peak arising 4 days prior to maturation. This
evaluation of GTH II was preceded by a progressive and significant rise GTH I
levels starting from 5.83 +/- 2.17 ng/ml 8 days before maturation and increasing
to more than 10 ng/ml on the day of maturation. Thus, the GTH II maturation surge
is not the only gonadotropic signal occurring before ovulation. The role of the
preovulatory GTH I increase remains unknown. After ovulation the secretory
profiles of the two hormones depended on the presence of absence of ovulated eggs
in the body cavity. There was a major increase in GTH I levels starting 4 days
after ovulation and egg stripping, reaching more than 25 ng/ml. Conversely, in
these fish the GTH II levels gradually decreased. In the fish which kept their
eggs in the body cavity the progress was reversed; 8 days after maturation, GTH
II increased to levels similar to those measured prior to maturation; the
presence of the eggs prevented an increase in GTH I. This seems to indicate that
postovulatory regulation of GTH I and GTH II secretion might involve ovarian
factors that act in an antagonistic fashion. The prevention of the increase in
GTH I levels in the presence of eggs suggests that as long as eggs are present in
the body cavity, the development of a new cycle of gametogenesis is not possible,
since GTH I is the gonadotropin mainly involved in controlling this phenomena.
GnRH cannot significantly stimulate GTH I secretion at any stage of
gametogenesis, even when its levels increased after ovulation. Other factors
antagonizing GnRH are involved. The well-known antagonistic effect of dopamine on
the GnRH stimulated GTH II secretion is fish is not involved since the dopamine
antagonist, pimozide, was ineffective in inducing a stimulatory action of GnRH on
GTH I secretion. Although GnRH can stimulate GTH II secretion from mid
vitellogenesis, the response to GnRH was not correlated with GTH II in blood.
These results suggest that GTH I and GTH II secretions are regulated by different
mechanisms and different factors.
PMID- 9653021
TI - Cloning of a full-length insulin-like growth factor-I complementary DNA in the
goldfish liver and ovary and development of a quantitative PCR method for its
measurement.
AB - Five forms of insulin-like growth factor-I (IGF-I) complementary DNA (cDNA) were
isolated by PCR from goldfish liver and ovary, using primers based on common carp
IGF-I sequence. In the goldfish liver, we cloned and sequenced three IGF-I forms
(1,2, and 3), and elucidated the full-length cDNA sequence using the 5'-and 3'
RACE. Two IGF-I forms (1 and 2) were cloned from the goldfish ovary and were
found to have differences with respect to both size and nucleotide sequence
compared to liver IGF-I. The entire liver IGF-I form 1 sequence was found to be
833 nucleotides long, containing a 483-nucleotide open reading from encoding 161
amino acids. The deduced amino acid sequence of the mature peptide was compared
to IGF-I sequences of other vertebrates, and found to have 97 and 93% similarity
to carp and salmon IGF-I, respectively, In this study we also developed a
competitive quantitative PCR method and demonstrated an increase in IGF-I
expression following treatments with growth hormone or gonadotropin-releasing
hormone in the goldfish liver.
PMID- 9653022
TI - Cloning and sequence analysis of a pituitary prolactin cDNA from the brushtail
possum (Trichosurus vulpecula).
AB - Overlapping cDNA partial clones of pituitary prolactin from the marsupial
brushtail possum (Trichosurus vulpecula) were isolated and sequenced. The
nucleotide and deduced amino acid sequences showed high sequence identity with
pig prolactin (84.3 and 92.5%, respectively) and all of the expected structural
features of a quadruped prolactin. A prolactin gene tree was constructed and
rates of evolution calculated for possum along with several mammalian and
nonmammalian prolactins. Possum prolactin was most closely linked to the
prolactins of eutherian mammals but branched from the main mammalian line well
before the eutherian prolactins. The prolactin/GH family shows variable rates of
evolution ranging from 0.3 substitutions/amino acid site/year x 10(9) for pig
prolactin to 7.0 substitutions/ amino acid site/year x 10(9) for the mouse. Since
divergence from the eutherian mammals, possum prolactin has shown a slow rate of
evolution (0.2 substitutions/ amino acid site/year x 10(9)). As expected, the
prolactin gene was expressed in the possum pituitary gland but not in the liver,
lung, kidney, heart, or mammary gland.
PMID- 9653023
TI - cDNA cloning of growth hormone from the brushtail possum (Trichosurus vulpecula).
AB - The full-length nucleotide sequence for the cDNA of growth hormone (GH) from the
marsupial brushtail possum (Trichosurus vulpecula) was determined using reverse
transcription followed by polymerase chain reaction (RT-PCR) and the 5'/3' rapid
amplification of cDNA ends (RACE) technique. Sequence information showed that the
possum GH cDNA was 831 base pairs (bp) in length, including the 5'untranslated
region (60 bp), the signal peptide (75 bp), the mature protein (573 bp, including
stop codon), and the 3' untranslated region (123 bp). At both the nucleotide and
the amino acid level (deduced from nucleotide sequence), there was a high degree
of sequence identity with pig and horse. These species were similar at 82.8 and
83.0% of bases at the nucleotide level and 91.6 and 91.1% at the amino acid
level, respectively. Northern analysis showed that GH mRNA is present in the
pituitary gland and was similar in size to that seen in other mammals
(approximately equal to 0.9 kb). Analysis of molecular evolution of GH in the
possum indicated that the rate of evolution is relatively slow (0.4
substitutions/ amino acid site/year x 10(9) and typical of that seen for
nonprimate mammals, which exhibit rates ranging between 0.2 and 1.3
substitutions/amino acid site/year x 10(9).
PMID- 9653024
TI - Effects of light on plasma somatolactin levels in red drum (Sciaenops ocellatus).
AB - The effects of illumination on circulating somatolactin (SL) levels were studied
in red drum sampled at various times during a 24-h light-dark cycle (l2L:l2D) and
during a 24-h period of constant light. Plasma SL concentrations were low in red
drum sampled during the light phase (0.6 +/- 0.05-1.1 +/- 0.2 ng/ml). The levels
were significantly elevated during the early-dark phase (5.8 +/- 1.0 ng/ml) and
declined during the late-dark phase (0.39 +/- 0.05 ng/ml). In contrast, plasma SL
levels remained low. (0.4 +/- 0.1-1.3 +/- 0.4 ng/ml) in fish sampled through a 24
h constant light period following a 1-week exposure to the light-dark cycle.
Circulating SL levels were also significantly elevated during the early-dark
phase in fish maintained under a reversed light-dark cycle. The role of the eyes
in mediation the SL response to light was evaluated by comparing circulating SL
levels in optic-tract sectioned and enucleated fish with those of intact
(control) fish. Plasma SL concentrations were significantly higher in optic-tract
sectioned and enucleated fish (6.5 +/- 0.9-13.8 +/- 1.5 ng/ml) than in control
fish (0.6 +/- 0.05-3.9 +/- 0.7 ng/ml) during both the early-dark phase and the
early-light phase of the 24-h light-dark cycle. The absence of significant
changes in plasma SL levels between the light and dark phases in optic-tract
sectioned and enucleated fish appears to be due to a loss of light perception in
these fish. Moreover, intact and sham-operated red drum maintained in constant
darkness had dramatically increased plasma SL levels (18.8 +/- 2.0-24.8 +/- 1.8
ng/ml). The present results are consistent with our earlier findings that plasma
SL levels are elevated in fish kept in constant darkness and in a dark-background
tank (reduction in overall light levels) during the light phase. Taken together,
these results suggest that plasma SL levels are elevated in red drum in the
absence of light and in response to low illumination. Interestingly, the
integument of the fish became light during the dark phase of the light-dark
cycle. In our earlier studies, the increase of plasma SL concentrations was
associated with aggregation of melanophores, and direct effects of SL on
melanophore aggregation were demonstrated. Overall, our studies with red drum
suggest a possible role of elevated SL levels on melanophore aggregation during
the dark phase of the 24-h day-night cycle.
PMID- 9653025
TI - Immunochemical identification of thyrotropes and gonadotropes in the pars
distalis and pars tuberalis of the toad (Bufo boreas) with reference to ontogenic
changes.
AB - Morphologically distinct secretory cells in the pituitary pars distalis and pars
tuberalis of larval and adult toads (Bufo boreas) immunoreactive cells in the
pars distalis. Thyrotropin immunoactivity appears in pars tuberalis and pars
distalis before gonadotropin immunoreactivity during early development. Antisera
which distinguish gonadotropes (stained with human and sea turtle LH beta) and
thyrotropes (stained with human TSH beta) as separate cell types in the pars
distalis of the adult toad immunoreact with the same single type of cell in the
pars distalis of the tadpole up through metamorphosis, suggesting the existence
of a single pluripotent, glycoprotein-producing precursor cell early in
development. Gonadotropin antisera do not react with the pars tuberalis in
tadpoles or adults.
PMID- 9653026
TI - Multiple forms of GnRH are released from perifused medial basal
hypothalamic/preoptic area (MBH/POA) explants in birds.
AB - Both chicken gonadotropin-releasing hormones I and II (cGnRH I and II) were
detected in abundant quantity by radioimmunoassay of extracts of Japanese quail
medial basal hypothalamic/preoptic area (MBH/POA) fragments that included the
median eminence (ME) region. However, in radioimmunoassayed extracts of Japanese
quail ME alone, the concentration of cGnRH I greatly exceeded that of cGnRH II
(approximately 450 pg/ME vs < 10 pg/ME). Likewise, cGnRH I and II were released
into perifusates from quail an turkey MBH/POA explants maintained in short-term
perifusion. Release of both forms occurred whether or not explants included the
ME region, i.e., from quail POA explants did not include the ME or from turkey
MBH/POA explants from which the ME region had been dissected out. This indicates
that neuropeptides released from areas other than the ME can be a major source of
neuropeptides detected in perifusates. Further, release of cGnRH I was altered
following the addition of norepinephrine to perfusion media, whereas cGnRH II
release was unaffected, again, whether or not explants included the ME. These
results demonstrate that the release of neurohemoral substances from perifused
explants cannot be assumed to represent regulated secretion from the ME.
PMID- 9653027
TI - Anatomy of hot spots in protein interfaces.
AB - Binding of one protein to another is involved in nearly all biological functions,
yet the principles governing the interaction of proteins are not fully
understood. To analyze the contributions of individual amino acid residues in
protein-protein binding we have compiled a database of 2325 alanine mutants for
which the change in free energy of binding upon mutation to alanine has been
measured (available at http://motorhead. ucsf.edu/thorn/hotspot). Our analysis
shows that at the level of side-chains there is little correlation between buried
surface area and free energy of binding. We find that the free energy of binding
is not evenly distributed across interfaces; instead, there are hot spots of
binding energy made up of a small subset of residues in the dimer interface.
These hot spots are enriched in tryptophan, tyrosine and arginine, and are
surrounded by energetically less important residues that most likely serve to
occlude bulk solvent from the hot spot. Occlusion of solvent is found to be a
necessary condition for highly energetic interactions.
PMID- 9653028
TI - Termination of packaging of the bacteriophage lambda chromosome: cosQ is required
for nicking the bottom strand of cosN.
AB - Termination of packaging of the lambda chromosome involves completion of
translocation of the DNA into the head shell, and conversion of the translocation
complex into a cleavage complex. The cleavage reaction introduces staggered nicks
into the downstream cosN to generate the right cohesive end of the chromosome.
cosQ, a site adjacent to cosN, was found to be required for nicking the bottom
strand of cosN; bottom strand nicking was also sequence-specific for bps at the
nick site. Nicking of the top strand of cosN (cosNL) was stimulated by cosQ, but
fidelity and efficiency of cosNL nicking were largely dictated by other cos
subsites (i.e. cosB and I2). Aberrant top-strand cleavage within cosQ was
observed in the absence of I2, and nicking at a site 8 nt 5' to the normal cosNL
nick site occurred in the absence of cosB. The presence of cosQ was found to be
insufficient to arrest DNA translocation in vivo, indicating that cosQ, per se,
is not a packaging stop signal. A model is presented in which the role of cosQ is
to depolarize the asymmetric arrangement of terminase protomers in the
translocation complex so that protomers are configured to match the 2-fold
rotational symmetry of cosN.
PMID- 9653029
TI - Sequence specificity of bacteriophage 434 repressor-operator complexation.
AB - The binding affinity of the bacteriophage 434 repressor for its DNA operator
depends strongly on the nature of two central base-pairs that are not in contact
with the dimeric protein. In order to investigate the origin of this sequence
specificity, we carried out molecular modelling of five model operators with
central TA, AT, CG, GC and IC sequences. The five oligomers were studied both
before and after complexation with the N-terminal binding domain of the 434
repressor. The relative importance of nucleic acid flexibility on operator
repressor binding was studied via a low frequency normal mode analysis using an
internal coordinate method that we developed recently. The results suggest a
higher twisting flexibility for TA and AT central steps than for CG, GC or IC
steps, but the differences appear to be too small to account for the strength of
repressor binding. An energetic analysis of the model operator-repressor
complexes reveals rather that the preference for A.T and T.A base-pairs is
electrostatic in origin and is linked to the presence of cationic Arg43 side
chains of repressor. This conclusion is supported by comparison with an R43A
mutant and correlates with the sequence dependence of the electrostatic potential
in the central minor groove of the operators.
PMID- 9653030
TI - Polymer chain statistics and conformational analysis of DNA molecules with bends
or sections of different flexibility.
AB - The worm-like chain model has often been employed to describe the average
conformation of long, intrinsically straight polymer molecules, including DNA.
The present study extends the applicability of the worm-like chain model to
polymers containing bends or sections of different flexibility. Several cases
have been explicitly considered: (i) polymers with a single bend; (ii) polymers
with multiple coplanar bends; (iii) polymers with two non-coplanar bends; and
(iv) polymers comprised of sections with different persistence lengths.
Expressions describing the average conformation of such polymers in terms of the
mean-square end-to-end distance have been derived for each case. For cases (i)
and (iv), expressions for the projection of the end-to-end vector onto the
initial orientation of the chain are presented. The expressions derived here have
been used to investigate DNA molecules with sequence-induced bending (A-tracts).
Mean-square end-to-end distance values determined from a large number of A-tract
containing DNA molecules visualized by scanning force microscopy resulted in an
average bend angle of 13.5 degrees per A-tract. A similar study was performed to
characterize the flexibility of double-strandedDNA molecules containing a single
stranded region. Analysis of their mean-square end-to-end distance yielded a
persistence length of 1.3 nm for single-stranded DNA.
PMID- 9653031
TI - Structure and dynamics of supercoil-stabilized DNA cruciforms.
AB - Understanding DNA function requires knowledge of the structure of local, sequence
dependent conformations that can be dramatically different from the B-form helix.
One alternative DNA conformation is the cruciform, which has been shown to have a
critical role in the initiation of DNA replication and the regulation of
transcription in certain systems. In addition, cruciforms provide a model system
for structural studies of Holliday junctions, intermediates in homologous DNA
recombination. Cruciforms are not thermodynamically stable in linear DNA due to
branch point migration, which makes their study using many biophysical techniques
problematic. Atomic Force Microscopy (AFM) was applied to visualize cruciforms in
negatively supercoiled plasmid DNA. Cruciforms are seen as clear-cut extrusions
on the DNA filament with the lengths of the arms consistent with the size of the
hairpins expected from a 106 bp inverted repeat. The cruciform exists in two
different conformations, an extended one with the angle of ca. 180 degrees
between the hairpin arms and a compact, X-type conformation, with acute angles
between the hairpin arms and the main DNA strands. The ratio of molecules with
the different conformations of cruciforms depends on ionic conditions. In the
presence of high salt or Mg cations, a compact, X-type conformation is highly
preferable. Remarkably, the X-conformation was highly mobile allowing the
cruciform arms to adopt a parallel orientation. The structure observed is
consistent with a model of the Holliday junction with a parallel orientation of
the exchanging strands.
PMID- 9653032
TI - Localization and characterization of the dimerization domain of holliday
structure resolving endonuclease VII of phage T4.
AB - Endonuclease VII (Endo VII) is a Holliday structure resolving enzyme of
bacteriophage T4. Its nucleolytic activity depends on subactivities, which in
order of execution are: (i) dimerization, (ii) binding to DNA, (iii) and cleavage
of DNA. In an effort to assign these subfunctions to the primary sequence of the
protein, a series of spontaneous point mutations deficient in DNA cleavage was
isolated. Some of these mutations affected the dimerization of Endo VII. Compared
with wild-type protein, which dimerizes completely in solution, more than 95% of
one of the mutant proteins (W87R) remained in the monomeric state. Only the
dimeric fraction of this protein bound to DNA. The dimerization domain of Endo
VII was mapped by truncating the gene from both ends and analysing the
dimerization ability of the purified peptides by crosslinking with
glutaraldehyde. The dimerization domain was thus determined to reside between
amino acid residues 55 and 105. Computer analyses predicted two alpha-helices (H2
and H3) in this section of the protein. As demonstrated by heterodimer formation,
two copies of helix H3, but only one copy of helix H2, are required for
dimerization. Helical wheel analyses revealed that both helices expose a
hydrophobic face along their axes, suggesting that hydrophobic interaction
between helices H3 mediate formation of Endo VII dimers, while helices H2
stabilize them.
PMID- 9653033
TI - Disulfide analysis reveals a role for macrophage migration inhibitory factor
(MIF) as thiol-protein oxidoreductase.
AB - The molecular mechanism of action of macrophage migration inhibitory factor
(MIF), a cytokine with a critical role in the immune and inflammatory response,
has not yet been identified. Here we report that MIF can function as an enzyme
exhibiting thiol-protein oxidoreductase activity. Using a decapeptide fragment of
MIF (MF1) spanning the conserved cysteine sequence motif Cys57-Ala-Leu-Cys60
(CALC), Cys-->Ser mutants (C57S MIF, C60S MIF, and C57S/C60S MIF) of human MIF
(wtMIF), and alkylated wtMIF, we show that this activity is mediated by the CALC
region and is important for the macrophage-activating properties of MIF. Both
wtMIF and MF1 were demonstrated to form an intramolecular disulfide bridge. Using
two common oxidoreductase assays, MIF was shown to enzymatically catalyze the
reduction of insulin and 2-hydroxyethyldisulfide (HED). Examination of wtMIF and
the mutants by far-UV circular dichroism spectroscopy (CD) together with
denaturation studies showed that substituting or reducing the cysteine residues
of CALC led to a reduced conformational stability of MIF but did not
significantly change its overall conformation. A functional role for the CALC
region was revealed by subjecting the mutants and alkylated wtMIF to the
enzymatic assays. Mutant C60S did not have any enzymatic activity while mutant
C57S had a reduced activity. Thiol-modified wtMIF that was alkylated under
oxidizing conditions was found to have full enzymatic activity, whereas
alkylation of wtMIF under reducing conditions completely eliminated MIF-mediated
redox activity. Importantly, further physiological relevance of the disulfide
motif was obtained by examining the mutants and alkylated MIF in an immunological
assay that involved the macrophage-activating properties of MIF. In this test,
mutant C60S was essentially inactive and mutant C57S was partly active,
indicating together that at least some of the cytokine-like biological activities
of MIF are dependent on the presence of cysteine 57 and 60. Again, use of the
alkylated MIF species confirmed the role of the cysteine motif for this MIF
activity. In conclusion, our results argue (a) that MIF exhibits enzymatic
oxidoreductase activity, (b) that this activity is dependent on the presence of
the catalytic center that is formed by cysteine residues 57 and 60, and (c) that
certain MIF-mediated immune processes are due to the cysteine-mediated redox
mechanism.
PMID- 9653034
TI - Escherichia coli 70 S ribosome at 15 A resolution by cryo-electron microscopy:
localization of fMet-tRNAfMet and fitting of L1 protein.
AB - Cryo-electron microscopy of the ribosome in different binding states with mRNA
and tRNA helps unravel the different steps of protein synthesis. Using over
29,000 projections of a ribosome complex in single-particle form, a three
dimensional map of the Escherichia coli 70 S ribosome was obtained in which a
single site, the P site, is occupied by fMet-tRNAfMet as directed by an AUG codon
containing mRNA. The superior resolution of this three-dimensional map, 14.9 A,
has made it possible to fit the tRNA X-ray crystal structure directly and
unambiguously into the electron density, thus determining the locations of
anticodon-codon interaction and peptidyltransferase center of the ribosome.
Furthermore, at this resolution, one of the distinctly visible domains
corresponding to a ribosomal protein, L1, closely matches with its X-ray
structure.
PMID- 9653035
TI - Expression of an antibody fragment at high levels in the bacterial cytoplasm.
AB - Recombinant antibody fragments expressed in the cytoplasm of cells have
considerable practical potential. However in the reducing environment of the
cytoplasm, the intradomain disulphide bonds are not formed and the fragments are
unstable and expressed in low yields. Here we attempted to overcome these
limitations. We first isolated an antibody single chain Fv fragment that binds
and activates an inactive mutant beta-galactosidase. We then subjected the gene
encoding the scFv fragment to random mutation in vitro by error-prone polymerase
chain reaction, and co-expressed the mutant beta-galactosidase and mutant
antibody fragments in lac- bacteria. By plating on limiting lactose, we selected
for antibody mutants with improved expression, and after four successive rounds
of mutation and selection, isolated an antibody fragment that is expressed in the
bacterial cytoplasm with yields of 0.5 g/l in a shaker flask (A600 nm of 5.5) and
3.1 g/l (A600 nm=33) in a fermentor. Analysis of the mutant antibody fragments
revealed that the disulphide bonds are reduced in the cytoplasm, and that the
fragments could be denatured and renatured efficiently under reducing conditions
in vitro. This shows that with a suitable method of screening or selection, it is
possible to make folded and functional antibody fragments in excellent yield in
the cytoplasm.
PMID- 9653036
TI - Refined structure of Cro repressor protein from bacteriophage lambda suggests
both flexibility and plasticity.
AB - The structure of the Cro repressor protein from phage lambda has been refined to
a crystallographic R-value of 19.3% at 2.3 A resolution. The re fined model
supports the structure as originally described in 1981 and provides a basis for
comparison with the Cro-operator complex described in the accompanying paper.
Changes in structure seen in different crystal forms and modifications of Cro
suggest that the individual subunits are somewhat plastic in nature. In addition,
the dimer of Cro suggests a high degree of flexibility, which may be important in
forming the Cro-DNA complex. The structure of the Cro subunit as determined by
NMR agrees reasonably well with that in the crystals (root-mean-square
discrepancy of about 2 A for all atoms). There are, however, only a limited
number of intersubunit distance constraints and, presumably for this reason, the
different NMR models for the dimer vary substantially among themselves
(discrepancies of 1.3 to 5.5 A). Because of this variation it is not possible to
say whether the range of discrepancies between the X-ray and NMR Cro dimers (2.9
to 7.5 A) represent a significant difference between the X-ray and solution
structures. It has previously been proposed that substitutions of Tyr26 in Cro
increase thermal stability by the "reverse hydrophobic effect", i.e. by exposing
40% more hydrophobic surface to solvent in the folded form than in the unfolded
state. The refined structure, however, suggests that Tyr26 is equally solvent
exposed in the folded and unfolded states. The most stabilizing substitution is
Tyr26-->Asp and in this case it appears that interaction with an alpha-helix
dipole is at least partly responsible for the enhanced stability.
PMID- 9653037
TI - Crystal structure of lambda-Cro bound to a consensus operator at 3.0 A
resolution.
AB - The structure of the Cro protein from bacteriophage lambda in complex with a 19
base-pair DNA duplex that includes the 17 base-pair consensus operator has been
determined at 3.0 A resolution. The structure confirms the large changes in the
protein and DNA seen previously in a crystallographically distinct low-resolution
structure of the complex and, for the first time, reveals the detailed
interactions between the side-chains of the protein and the base-pairs of the
operator. Relative to the crystal structure of the free protein, the subunits of
Cro rotate 53 degrees with respect to each other on binding DNA. At the same time
the DNA is bent by 40 degrees through the 19 base-pairs. The intersubunit
connection includes a region within the protein core that is structurally
reminiscent of the "ball and socket" motif seen in the immunoglobulins and T-cell
receptors. The crystal structure of the Cro complex is consistent with virtually
all available biochemical and related data. Some of the interactions between Cro
and DNA proposed on the basis of model-building are now seen to be correct, but
many are different. Tests of the original model by mutagenesis and biochemical
analysis corrected some but not all of the errors. Within the limitations of the
crystallographic resolution it appears that operator recognition is achieved
almost entirely by direct hydrogen-bonding and van der Waals contacts between the
protein and the exposed bases within the major groove of the DNA. The
discrimination of Cro between the operators OR3 and OR1, which differ in sequence
at just three positions, is inferred to result from a combination of small
differences, both favorable and unfavorable. A van der Waals contact at one of
the positions is of primary importance, while the other two provide smaller,
indirect effects. Direct hydrogen bonding is not utilized in this distinction.
PMID- 9653038
TI - Crystal structure of the ternary complex of E. coli purine nucleoside
phosphorylase with formycin B, a structural analogue of the substrate inosine,
and phosphate (Sulphate) at 2.1 A resolution.
AB - The ternary complex of purine nucleoside phosphorylase from E. coli with formycin
B and a sulphate or phosphate ion crystallized in the hexagonal space group P6122
with unit cell dimensions a=123.11, c=241.22 A and three monomers per asymmetric
unit. The biologically active hexamer is formed through 2-fold crystallographic
symmetry, constituting a trimer of dimers. High-resolution X-ray diffraction data
were collected using synchrotron radiation (Daresbury, England). The crystal
structure was determined by molecular replacement and refined at 2.1 A resolution
to an R-value of 0.196. There is one active centre per monomer, composed of
residues belonging to two subunits of one dimer. The phosphate binding site is
strongly positively charged and consists of three arginine residues (Arg24, Arg87
and Arg43 from a neighbouring subunit), Ser90 and Gly20. It is occupied by a
sulphate or phosphate anion, each oxygen atom of which accepts at least two
hydrogen bonds or salt-bridges. The sulphate or phosphate anion is also in direct
contact with the ribose moiety of formycin B. The ribose binding site is composed
of Ser90, Met180, Glu181 and His4, the latter belonging to the neighbouring
subunit. The base binding site is exposed to solvent, and the base is
unspecifically bound through a chain of water molecules and aromatic-aromatic
interactions. In all monomers the nucleosides are in the high syn conformation
about the glycosidic bonds with chi in the range 100 to 130 degrees. The
architecture of the active centre is in line with the known broad specificity and
the kinetic properties of E. coli PNP.
PMID- 9653039
TI - Contribution of individual residues to formation of the native-like tertiary
topology in the alpha-lactalbumin molten globule.
AB - Molten globules are partially folded forms of proteins that have native-like
secondary structure and a compact geometry, but often without rigid, specific
side-chain packing. Recently, the molten globule of alpha-lactalbumin (alpha-LA)
has been shown to adopt a native-like tertiary topology, mainly localized in the
alpha-helical domain. This native-like topology is reflected by the high
effective concentration (Ceff) for formation of the 28-111 disulfide bond, which
is approximately 10 to 40 times higher than the Ceff for formation of any non
native disulfide bond in the alpha-helical domain. In order to understand the
mechanism for formation of the native-like tertiary topology, we substituted
alanine for each of the 23 buried residues in the alpha-helical domain of alpha
LA and determined the effect of these substitutions on the Ceff for formation of
the 28-111 disulfide bond. Our results indicate that a subset of hydrophobic
residues is most important for formation of the native-like topology. These
residues form a densely packed core in the three-dimensional structure of alpha
LA. In contrast, the less important residues consist of both hydrophobic and
hydrophilic amino acids located at peripheral positions. These results suggest
that a relatively small number of hydrophobic residues may be sufficient for
specifying the overall structure of a protein during early stages of protein
folding.
PMID- 9653041
TI - Introduction.
PMID- 9653040
TI - A specific hydrophobic core in the alpha-lactalbumin molten globule.
AB - Molten globules are partially structured protein folding intermediates that adopt
a native-like overall backbone topology in the absence of extensive detectable
tertiary interactions. It is important to determine the extent of specific
tertiary structure present in molten globules and to understand the role of
specific side-chain packing in stabilizing and specifying molten-globule
structure. Previous studies indicate that a small degree of specific side-chain
packing stabilizes the structures of the cytochrome c, apomyoglobin, and
staphylococcal nuclease molten globules. Here we investigate the extent of
specific side-chain packing in the molten globule of alpha-lactalbumin (alpha
LA), a highly fluctuating, non-cooperatively formed molten globule. By analyzing
a set of point mutations in the helical domain of alpha-LA, we have identified a
stabilizing hydrophobic core. Moreover, this core corresponds to a previously
identified structural subdomain and likely contains some native-like packing
interactions. Our results suggest that native-like packing of core amino acids
helps stabilize molten globules and that some specific interactions can exist in
even highly dynamic, fluctuating species.
PMID- 9653042
TI - Introduction: HIV co-receptors solve old questions and raise many new ones.
PMID- 9653043
TI - Microbial corruption of the chemokine system: an expanding paradigm.
AB - The chemokine signaling system includes more than 40 secreted pro-inflammatory
peptides and 12 G protein-coupled receptors that together orchestrate specific
leukocyte trafficking in the mammalian immune system, ideally for anti- microbial
defense and tissue repair processes. Paradoxically and perversely, some
chemokines and chemokine receptors are also promicrobial factors and facilitate
infectious disease, the result of either exploitation or subversion by specific
microbes. Two modes of exploitation are known: usage of cellular chemokine
receptors for cell entry by intracellular pathogens, including HIV, and usage of
virally-encoded chemokine receptors for host cell proliferation. Likewise, two
modes of subversion are known: virally-encoded chemokine antagonists and virally
encoded chemokine scavengers. Understanding how microbes turn the tables on the
chemokine system may point to new methods to prevent or treat infection, or, more
generally, to treat inappropriate chemokine-mediated inflammation.
PMID- 9653044
TI - A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in
development, hematopoiesis and HIV infection.
AB - PBSF/SDF-1 is a CXC chemokine which has unique functions among chemokines. It is
essential for viability of the embryo, B lymphopoiesis, bone marrow hematopoiesis
and cardiogenesis. A receptor for PBSF/SDF-1 was shown to be CXCR4 that is an
entry co-receptor for T cell line-tropic HIV-1. Although murine cells had been
thought to have no functional co-receptors, murine CXCR4 allowed entry of HIV-1
into target cells with human CD4. In addition, a small molecule CXCR4 inhibitor
that blocks HIV-1 entry was identified.
PMID- 9653045
TI - Chemokine receptor allelic polymorphisms: relationships to HIV resistance and
disease progression.
AB - It is now well established that an array of CC and CXC chemokine receptors, in
association with the CD4 molecule, can interact with the HIV-1 gp120 protein to
facilitate viral fusion. A 32bp deletion in the CC chemokine receptor CCR5, the
major M-tropic viral co-receptor, provides considerable protection against HIV-1
transmission and has been associated with a delay in disease progression. The
effects of the Delta32 allele appear to be mediated through the phenotype of CCR5
expression as opposed to genotype. Here we discuss the potential effects that the
Delta32 allele and other polymorphisms in the chemokine receptor repertoire may
have on both HIV-1 transmission and disease progression.
PMID- 9653046
TI - The role of co-stimulation in regulation of chemokine receptor expression and HIV
1 infection in primary T lymphocytes.
AB - Fusion and entry of the human immunodeficiency virus (HIV) into CD4(+) T
lymphocytes requires expression of CD4 and a coreceptor. At least eight chemokine
receptors can serve as coreceptors for HIV. Accumulating evidence indicates that
multiple factors, including the state of cellular differentia- tion and
activation, regulate the expression of alpha- and beta-chemokine receptors on
lymphocytes. For example, binding of antibodies to the CD28 coreceptor can
downregulate expression of beta-chemokine receptors, and this appears to have
important consequences on the susceptibility of CD4(+) T lymphocytes to infection
by HIV-1. In contrast, binding of the natural CD28 ligand B7 or antibodies to the
CD28 homologue CTLA-4 can upregulate CCR5 expression, sug- gesting a reciprocal
interaction between CD28 and CTLA-4 and the regulation of beta-chemokine receptor
expression. Thus, the CD28/CTLA-4/B7 co-stimulation pathway is identi- fied as a
potential novel target for the control of susceptibility to some strains of HIV-1
infection.
PMID- 9653047
TI - Chemokine receptors in HIV-1 infection of the central nervous system.
AB - Several members of the chemokine receptor are used as coreceptors for HIV-1
infection in the central nervous system (CNS). CCR5 and CCR3 are coreceptors
together with CD4 for HIV-1 infection of microglia, the major target for HIV-1
infection in the CNS. Microglia express CXCR4, but their infection by HIV-1
viruses that use only CXCR4 as a coreceptor is relatively inefficient. CXCR4 is
also expressed in subpopulations of neurons that are resistant to HIV-1
infection. Additional orphan chemokine receptors that can mediate HIV-1 or SIV
entry are expressed in the brain or neurally-derived cell lines, but their role
in CNS infection has not been defined. The pattern of chemokine receptor
expression in the brain is likely to determine the tropism of HIV-1 for
particular CNS target cells and to impact inflammatory and degenerative
mechanisms associated with CNS infection.
PMID- 9653048
TI - The function of simian chemokine receptors in the replication of SIV.
AB - The long sought co-receptors for primate lentiviruses were identified as
belonging to a large family of cell surface proteins - the seven transmembrane
proteins. These proteins normally function as cell surface receptors for
chemokines and other ligands. The families of genetically divergent Simian
Immunodeficiency Viruses (SIV), which include the origins of HIV-1 and HIV-2, use
simian and human chemokine receptors as their co-receptors. SIVmac, SIVsm, SIVagm
and SIVcpz use monkey and human CCR5 for cell fusion and entry. Human-derived
STRL33 (BONZO) and human-derived GPR-15 (BOB) are also used, but with variable
efficiency. True primary strains of SIVsm, obtained from the naturally infected
simian host, the sooty mangabey, use simian and human CCR5 in a strongly CD4
dependent manner. However, some brain and lymphoid isolates from the experimental
simian host, the macaque use CCR5 independently of CD4. Unlike T cell line
adapted (TCLA) CXCR4-tropic HIV strains (XR4 HIV), only a few laboratory SIV
strains use CXCR4 for entry. Macaque and mangabey CXCR4 are fully functional,
because they are highly efficient for entry of XR4 HIV. The CCR5 co-receptor is
used by three of four SIV families tested thus far. The fourth family,
represented by the isolate, S1Vrcm95GB1, is unique among SIV and HIV in its use
of CCR2b but not CCR5.
PMID- 9653049
TI - G protein-coupled receptors in HIV and SIV entry: new perspectives on lentivirus
host interactions and on the utility of animal models.
AB - Entry of primate lentiviruses into target cells has recently been shown to depend
upon the interaction of the viral envelope glycoprotein with CD4 and one or more
members of the G protein-coupled receptor (GPCR) family of transmembrane
proteins. In vivo, the transmission of HIV-1 infection generally requires viral
strains that utilise chemokine recep- tor CCR5, and these strains prevail during
the early course of infection. Strains isolated later, in the course of
progression to immunodeficiency, are often CXCR4-tropic or are dual tropic for
both chemokine receptors. SIV isolates also use CCR5 but are only rarely specific
for CXCR4. Instead, SIVs use two orphan members of the GPCR family, named
Bonzo/STRL33/TYMSTR and BOB/GPR15. Strains of HIV-2, which are closely related to
the SIVs, also often utilise CXCR4, CCR5, BOB and/or Bonzo. Additional GPCR
family members have also been shown to be utilised by various strains of HIV and
SIV, albeit less efficiently and less frequently. Here we discuss the potential
relationship between receptor specificity and viral pathogenesis as well as
efforts to develop animal model systems to study the mechanism of disease
progression.
PMID- 9653050
TI - Structure-function studies of the HIV-1 coreceptors.
AB - Ten seven-transmembrane-domain G protein-coupled receptors have been identified
that are functional HIV-1, HIV-2 and SIV coreceptors. However, the specific
structures these receptors have in common that enable them to mediate HIV entry
are unknown. Structure-function analyses have revealed that the determinants of
coreceptor activity are distinct for each coreceptor, coreceptor activity is
dependent on multiple extracellular domains, and various envelope proteins may
interact differently with the same coreceptor. G protein coupling and receptor
internalization are not required for fusion and infection of established cell
lines, or for inhibition of infection by chemokines. The structure-function
studies have also helped determine the mechanism by which previously described
small molecules inhibit HIV-1 entry. Finally, these studies have led to a
hypothesis as to how coreceptor utilization evolves during the course of an
infection.
PMID- 9653051
TI - Structural interactions between chemokine receptors, gp120 Env and CD4.
AB - Seven transmembrane segment (7TMS) receptors for chemokines and related molecules
have been demonstrated to be essential, in addition to CD4, for HIV and SIV
infection. The beta-chemokine receptor CCR5 is the primary, perhaps sole, co
receptor for HIV-1 during the early and chronic phases of infection and supports
infection by most primary HIV-1 and many SIV isolates. Late-stage primary and
laboratory-adapted HIV-1, HIV-2, and SIV isolates can use other 7TMS receptors.
CXCR4 appears especially important in late-stage HIV infection; several related
receptors can also be used. The specificity of SIV viruses is similar.
Commonalities among these receptors, combined with analyses of mutated molecules,
indicate that discrete, conformationally-dependent sites on the chemokine
receptors determine their association with the third variable and conserved
regions of viral envelope glycoproteins. These studies are useful for elucidating
the mechanism and molecular determinants of HIV-1 entry, and of inhibitors to
that entry.
PMID- 9653052
TI - A physiologically based pharmacokinetic description of the oral uptake, tissue
dosimetry, and rates of metabolism of bromodichloromethane in the male rat.
AB - Bromodichloromethane (BDCM), a trihalomethane (THM) and water chlorination by
product, induces cancer in several tissues in experimental animals, including
target tissue sites where increased incidences of human cancer have been linked
to consumption of chlorinated water. The purpose of the present study was to
examine the effects of vehicle of administration on the pharmacokinetics of
orally administered BDCM and to further develop and validate a physiologically
based pharmacokinetic (PBPK) model to describe BDCM absorption, tissue dosimetry,
and rates of metabolism for both oil and 10% Emulphor vehicles. Estimates of oral
absorption rate constants were determined by fitting blood and exhaled breath
chamber concentration-time curves obtained following gavage of male F344 rats
with 50 or 100 mg BDCM/kg in corn oil or 10% Emulphor using a previously
published multicompartmental gastrointestinal tract submodel (Semino et al.,
Toxicology 117, 25-33, 1997) linked to a PBPK model. Independently estimated oral
uptake and metabolic rate constants accurately described kidney BDCM
concentrations and plasma bromide ion levels without adjustment. This observation
increases our confidence in model structure and values of parameter estimates.
Liver BDCM concentrations were simulated, but with less accuracy than kidney
dosimetry simulations, following incorporation of BDCM loss to metabolism during
sample preparation. This model describes BDCM tissue dosimetry and metabolism
following oral gavage and can be utilized in estimating rates of formation of
reactive metabolites in target tissues. Estimates of tissue dosimetry and levels
of toxic intermediates can be incorporated into a risk assessment model for BDCM
induced toxicity and carcinogenicity.
PMID- 9653053
TI - The role of IgG1 and IgG2 in trimellitic anhydride-induced allergic response in
the guinea pig lung.
AB - Trimellitic anhydride (TMA) is a small molecular weight chemical used in the
paint and plastics industry that can cause asthma-like symptoms in humans. Guinea
pigs sensitized intradermally with TMA will respond to antigen challenge with
asthma-like symptoms, including an immediate bronchoconstriction and a delayed
cellular infiltration into the lung, particularly eosinophil infiltration.
Sensitized guinea pigs produce TMA-specific IgG1, which is thought to be
important in asthmatic reactions in this animal model; however, they also produce
TMA-specific IgG2 antibody. The purpose of the present study was to determine the
role of IgG1 and IgG2 in the TMA-induced immediate bronchoconstriction and
delayed cellular infiltration in the guinea pig. Guinea pigs were passively
sensitized by intratracheal instillation of TMA-specific IgG2, an antibody
preparation enriched with TMA-specific IgG1, or a combination of the two. The
allergic response was induced by intratracheal instillation of TMA conjugated to
guinea pig serum albumin (TMA-GPSA). A significantly greater bronchoconstrictor
response was observed in animals sensitized with a combination of the IgG2 and
IgG1 preparation compared to those sensitized with IgG2 or the IgG1 preparation
alone. Cellular infiltration was quantified 24 h after antigen challenge by
differential cell counts of bronchoalveolar lavage (BAL) cells as well as by
using eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity as a measure
of the numbers of eosinophils and neutrophils, respectively. In the BAL,
passively sensitizing with IgG2 alone resulted in an increase in both TMA-induced
MPO and EPO activity. In contrast, in the lung, passively sensitizing with a
partially purified preparation of TMA-specific IgG1 alone resulted in a
significant increase in TMA-induced EPO activity. Passively sensitizing with IgG2
in conjunction with the IgG1 preparation resulted in an enhanced cellular
infiltration and lung injury over that seen with either antibody preparation
alone. These data demonstrate an augmentation of IgG1-mediated responses by the
addition of IgG2 and suggest a significant role for both subclasses of IgG
antibodies in this guinea pig model of TMA-induced occupational asthma.
PMID- 9653054
TI - Responsiveness of the adult male rat reproductive tract to 2,3,7,8
tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1
induction, and Ah receptor down-regulation.
AB - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either in adulthood or
during late fetal and early postnatal development causes a variety of adverse
effects on the male rat reproductive system. It was therefore of interest to
identify male rat reproductive organs and cell types within these organs that
might be direct targets of TCDD exposure. Because TCDD toxicity could possibly be
the result of alterations in gene transcription mediated by the TCDD/aryl
hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex, the presence
of the AhR and ARNT in the various organs of the adult male reproductive tract
was examined using Western blotting. Both proteins were detectable in all organs
examined (testis, epididymis, vas deferens, ventral prostate, dorsolateral
[combined dorsal and lateral] prostate, and seminal vesicle). Although technical
difficulties precluded the immunohistochemical evaluation of AhR distribution in
these organs, ARNT was localized in all organs in a variety of cell types,
including germ cells, epithelial cells, fibroblasts, smooth muscle cells, and
endothelial cells. Subcellular localization varied across organs and across cell
types within these organs. In order to determine whether TCDD exposure could
alter gene expression in these organs, animals were dosed with TCDD (25
micrograms/kg po) or vehicle and euthanized at 24 h, and cytochrome P4501A1
(CYP1A1) expression was evaluated. By Western blotting, only the ventral and
dorsolateral prostates exhibited significant induction of CYP1A1.
Immunohistochemistry confirmed this induction and localized CYP1A1 expression to
epithelial cells of the ventral and lateral lobes of the prostate.
Immunohistochemistry also revealed CYP1A1 induction in select epithelial cells in
the epididymis and seminal vesicle, as well as endothelial cells in the vas
deferens and seminal vesicle. No induction was observed in the testis. Finally,
AhR and ARNT expression in TCDD-exposed and control animals was evaluated by
Western blotting. Results revealed no effect of TCDD exposure on ARNT protein
expression, while AhR expression was decreased to 5-51% of control in all organs
examined. In summary, both AhR and ARNT were expressed in all organs of the adult
male rat reproductive tract examined, and epithelial and/or endothelial cells
within each of these organs (with the exception of the testis) were responsive to
TCDD exposure in terms of CYP1A1 induction. In addition, all tissues exhibited
marked reductions in AhR protein content after TCDD exposure that did not
correlate with the magnitude of the CYP1A1 response.
PMID- 9653055
TI - In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p
dioxin impairs prostate development. 1. Effects on gene expression.
AB - In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure
decreases rat prostate weight without decreasing circulating androgen
concentrations. Because one mechanism by which TCDD is thought to cause toxicity
is by aryl hydrocarbon receptor (AhR)-mediated alterations in gene transcription,
the goals of this study were to determine whether the developing prostate
expresses the AhR and its dimerization partner, the AhR nuclear translocator
(ARNT); to determine whether in utero and lactational TCDD exposure is capable of
directly activating gene transcription in the developing prostate; and to
identify prostatic mRNAs that exhibit altered abundance in response to in utero
and lactational TCDD exposure. Pregnant Holtzman rats were administered TCDD (1.0
microgram/kg po) or vehicle on Gestation Day (GD) 15, and male offspring were
euthanized between Postnatal Days (PNDs) 1 and 63. Using reverse transcriptase
polymerase chain reaction (RT-PCR), mRNAs encoding the AhR and ARNT were detected
in both ventral and dorsolateral prostates from control animals throughout
postnatal development. ARNT protein was expressed in the majority of stromal
nuclei early in development, whereas ARNT expression in the prostate epithelium
was initially cytoplasmic but became nuclear as development progressed. GD 15
TCDD exposure increased cytochrome P4501A1 (CYP1A1) mRNA and protein in whole
prostates between PNDs 7 and 21. In these TCDD-exposed animals, CYP1A1 protein
was localized to the epithelium. In order to define other genes in the developing
prostate that might be regulated by TCDD at the level of mRNA, RNA samples from
PND 21 whole prostates from control and TCDD-exposed animals were compared using
mRNA differential display. Although no growth-regulatory candidates were
identified using this screening technique, a ventral prostate-specific, androgen
regulated mRNA (20-kDa protein) was identified that seemed to be downregulated by
TCDD exposure. Northern blot analysis confirmed this decrease at PND 21 and
further showed that the downregulation was transient. Similar results were
obtained for four additional androgen-regulated prostatic mRNAs (prostatic
binding protein [PBP], Royal Winnipeg Ballet [RWB], probasin, and dorsal protein
1 [DP-1]), all of which are markers of a differentiated ductal epithelium. In
contrast, TCDD exposure of adult male rats (25 micrograms TCDD/kg, 24 h) greatly
induced CYP1A1 mRNA without affecting the abundance of prostate-specific,
androgen-regulated mRNAs. These results suggest that the transient decreases in
androgen-regulated prostatic mRNA abundance observed in response to in utero and
lactational TCDD exposure were probably not the result of direct action of the
activated AhR on these genes but instead were reflective of a TCDD-induced delay
in prostate development.
PMID- 9653056
TI - In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p
dioxin impairs prostate development. 2. Effects on growth and
cytodifferentiation.
AB - In the male Holtzman rat, in utero and lactational 2,3,7,8-tetrachlorodibenzo-p
dioxin (TCDD) exposure decreases prostate weight without inhibiting testicular
androgen production or decreasing circulating androgen concentrations. Therefore,
the present study sought to characterize effects of TCDD exposure on prostate
development, from very early outgrowth from the urogenital sinus (Gestation Day
[GD] 20) until rapid growth and differentiation are essentially complete
(Postnatal Day [PND] 32). Pregnant Holtzman rats were administered a single dose
of TCDD (1.0 microgram/kg po) or vehicle on GD 15 and offspring were exposed via
placental transfer (GD 20 euthanasia) or placental and subsequent lactational
transfer until euthanasia (if before PND 21) or weaning. Results show that the
prostatic epithelial budding process was impaired by in utero TCDD exposure, as
evidence by significant decreases in the number of buds emerging from dorsal,
lateral, and ventral aspects of the GD 20 urogenital sinus. Ventral prostate cell
proliferation index was significantly decreased on PND 1 but was similar to or
higher than control at later times, whereas apoptosis was an extremely rare event
in ventral prostates from both control and TCDD-exposed animals. Delays were
noted in the differentiation of pericordal smooth muscle cells and luminal
epithelial cells. In addition, ventral prostates from approximately 40% of TCDD
exposed animals examined on PNDs 21 and 32 exhibited alterations in the
histological arrangement of cell types that could not be explained by a
developmental delay. Compared to controls, these ventral prostates exhibited a
disorganized, hyperplastic epithelium containing fewer luminal epithelial cells
and an increased density or continuous layer of basal epithelial cells, as well
as thicker periductal smooth muscle sheaths. In addition, in ventral prostates
from TCDD-exposed animals, the intensity of androgen receptor staining was
relatively low in the central and distal epithelium, and the number of androgen
receptor-positive cells was relatively high in the periductal stroma. These data
suggest that in utero and lactational TCDD exposure interferes with prostate
development by decreasing very early epithelial growth, delaying
cytodifferentiation, and, in the most severely affected animals, producing
alterations in epithelial and stromal cell histological arrangement and the
spatial distribution of androgen receptor expression that may be of permanent
consequence.
PMID- 9653057
TI - Glia increase degeneration of hippocampal neurons through release of tumor
necrosis factor-alpha.
AB - This study characterizes the role of glial cells in chemically induced
neurodegeneration. We evaluated the effect of trimethyltin, a trisubstituted
organotin compound that elicits distinct lesions in the central nervous system in
vivo, on a sandwich co-culture of neurons and glia. Exposure of a 98% pure
culture of rat hippocampal neurons to 0.1-1 microM trimethyltin for 24 h caused
neural cell death and nuclear changes typical of apoptosis; at these doses glial
cells viability was not affected but the cells released significant amounts of
tumor necrosis factor-alpha (TNF-alpha). Neuronal apoptosis and TNF-alpha release
from glial cells both increased when the two cell types were exposed together to
trimethyltin, which indicates synergy. Treatment of a neuron-glia co-culture with
TNF-alpha antibody prevented the increase in neuronal apoptosis, and TNF-alpha
administration induced apoptosis in hippocampal cells. We conclude that glial
cells and TNF-alpha both modulate trimethyltin-induced neurodegeneration.
PMID- 9653059
TI - Dichloroacetate and trichloroacetate promote clonal expansion of anchorage
independent hepatocytes in vivo and in vitro.
AB - Dichloroacetate (DCA) and trichloroacetate (TCA) are hepatocarcinogenic by
products of water chlorination and metabolites of several industrial solvents. To
determine whether DCA and TCA promote the clonal expansion of anchorage
independent liver cells in vitro, a modification of the soft agar assay (over
agar assay) was utilized to quantitate growth and analyze phenotype of anchorage
independent hepatocellular colonies. Hepatocytes from naive male B6C3F1 mice were
isolated and cultured with 0-2.0 mM DCA or TCA over agar for 10 days, at which
time colonies of eight cells or more were scored. Both DCA and TCA promoted the
formation of anchorage-independent colonies in a dose-dependent manner.
Immunocytochemical analysis using a c-Jun antibody demonstrated that colonies
promoted by DCA were primarily c-Jun+, whereas TCA-promoted colonies were
primarily c-Jun-. This corresponds to the differences in c-Jun immunoreactivity
reported in tumors induced by DCA and TCA. Neither DCA nor TCA induced c-Jun
expression in hepatocyte monolayers, indicating that these haloacetates
selectively affect subpopulations of anchorage-independent hepatocyts. The
latency of colony formation was decreased by the concentration of DCA, although
the same number of colonies appeared after 25 days in culture at all DCA
concentrations used. The plating density of hepatocytes also affected colony
formation. At lower cell densities, promotion of colony formation by DCA was
significantly reduced. Pretreatment of male B6C3F1 mice with 0.5 g/liter DCA in
drinking water resulted in a fourfold increase in in vitro colony formation above
hepatocytes isolated from naive mice, suggesting that DCA is promoting the clonal
expansion of anchorage-independent hepatocytes in vivo. Results from this study
indicate that DCA and TCA promote the survival and growth of initiated cells.
Furthermore, results from over agar assays reflect observations made in vivo,
indicating this assay provides a valid means to investigate the mechanism by
which chemicals promote clonal expansion of initiated hepatocytes.
PMID- 9653058
TI - Effect of rodent hepatocarcinogenic peroxisome proliferators on fatty acyl-CoA
oxidase, DNA synthesis, and apoptosis in cultured human and rat hepatocytes.
AB - The effects of the rodent hepatocarcinogens clofibric acid and diprofibrate on
the activity of the peroxisomal fatty acyl-CoA oxidase, DNA synthesis, and
apoptosis were compared in cultured rat and human hepatocytes. Rat hepatocytes
expressed a 10-fold greater level of the peroxisomal fatty acyl-CoA oxidase
compared to human hepatocytes. At the highest concentration (1.0 mM), both drugs
induced a two- to threefold increase in this enzyme activity in both rat and
human hepatocytes. Ciprofibrate (0.1 and 0.2 mM) caused a twofold increase in DNA
synthesis in rat hepatocytes, whereas clofibric acid had no effect on DNA
synthesis in these cells. In contrast, increasing concentrations of both
clofibric acid and ciprofibrate produced inhibition of DNA synthesis in human
hepatocytes. By using the terminal transferase dUTP-biotin nick end labeling
technique, it was observed that 0.1 and 0.2 mM clofibric acid and ciprofibrate
suppressed transforming growth factor-beta (TGF beta)-induced apoptosis by 50% in
rat hepatocytes, but they had no effect on TGF beta-induced apoptosis in human
hepatocytes. Although clofibric acid and ciprofibrate diminished TGF beta-induced
apoptosis, they had no effect on the basal apoptotic levels in the rat hepatocyte
cultures. However, both drugs significantly increased the percent of apoptotic
cells in the human hepatocyte cultures. It is concluded that primary rat and
human hepatocyte cultures respond differently to peroxisome proliferators. The
differences in effects on DNA synthesis and apoptosis support the hypothesis that
human liver cells are refractory to peroxisome proliferator-induced
hepatocarcinogenesis.
PMID- 9653060
TI - Interspecies scaling of clearance and volume of distribution for horse antivenom
F(ab')2.
AB - F(ab')2 fragments are sometimes preferred to whole IgG for therapeutic or
diagnostic uses. Preclinical pharmaceutical development studies are necessary
before their use in humans. Here we propose an allometric approach among three
mammalian species to predict F(ab')2 pharmacokinetic parameters in humans. Plasma
disposition of horse antivenom F(ab')2 fragments labeled with iodine 125 was
studied at a dose of 10 mg/kg i.v. in mice, rats, and rabbits. Using the
allometric method, we demonstrate that the pharmacokinetic parameters that
correlated with body weight were distribution volume (Vdc (ml) = 0.125 W0.87;
Vdss (ml) = 0.251 W0.87; Vd beta (ml) = 0.290 W0.87, r2 = 1), total clearance
(Cltot (ml/h) = 0.049 W0.53, r2 = 0.99), and terminal half-life (t1/2 beta (h) =
4.35 W0.33). The F(ab')2 plasma concentration-time data plotted as a complex
Dedrick relationship were superimposable. Using these allometric techniques,
Vdss, Vd beta, Cltot, and t1/2 beta were calculated as 4.12 liter, 4.78 liter,
19.07 ml/h, and 7.2 days, respectively, for a human subject of 70 kg body wt.
Predicted human pharmacokinetic parameters were comparable for volume of
distribution with the value reported by Hnatowich et al. (Cancer Res. 47, 6111
6117, 1987): 3.5 liter. However, the clearance was six-fold lower than values
given by Hnatowich et al. (130 ml/h) and Ho et al.
PMID- 9653061
TI - Role of oxidative stress in the selective toxicity of dieldrin in the mouse
liver.
AB - Dieldrin, an organochlorine insecticide, induces hepatic tumors in mice but not
in rats. Although the mechanism(s) responsible for this species specificity is
not fully understood, accumulating evidence indicates that oxidative stress may
be involved. This study examined the association of dieldrin-induced hepatic DNA
synthesis with the modulation of biomarkers of oxidative damage to lipids
(malondialdehyde [MDA]) and DNA (8-hydroxy-2-deoxyguanosine [oh8dG]), in male
B6C3F1 mice and F344 rats fed dieldrin (0.1, 1.0, or 10 mg/kg diet) for 7, 14,
28, and 90 days. The nonenzymatic components of the antioxidant defense system
(ascorbic acid, glutathione, and alpha-tocopherol) were also examined. Increased
urinary MDA was observed in mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet for 7,
14, 28, and 90 days; while increased hepatic MDA was seen only after 7 days in
mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet and after 14 days in mice fed 10
mg/kg diet. In rats, dieldrin had no effect on either hepatic MDA or urine MDA
levels after 7, 14, and 28 days of treatment. A dose-dependent increase in
urinary MDA was observed in rats at the 90-day sampling time. The only
significant elevation in urinary or hepatic oh8dG content was limited to urinary
oh8dG in mice fed 10 mg/kg dieldrin diet for 14 days. Dietary dieldrin produced
sustained decreases in hepatic and serum alpha-tocopherol and sustained
elevations in hepatic ascorbic acid in both mice and rats. Rats, however,
possessed a three- to four-fold higher content of endogenous or basal (control)
hepatic alpha-tocopherol; and, even when fed 10 mg dieldrin/kg diet, the levels
of hepatic alpha-tocopherol were maintained at higher levels than those of mice
fed control diet. In both rats and mice fed dieldrin, transient (14 and 28 days
on diet) elevations in hepatic glutathione were observed. These data support the
hypothesis that the species specificity of dieldrin-induced hepatotoxicity may be
related to dieldrin's ability to induce oxidative stress in the liver of mice,
but not in rats. Only in mice fed dieldrin was a temporal association of
increases in hepatic MDA content and hepatic DNA synthesis seen, suggesting that
oxidative damage (shown by increased lipid peroxidation) may be involved in early
events in dieldrin-induced hepatocarcinogenesis. Rats may be protected from
dieldrin-induced oxidative stress by a more effective antioxidant defense system,
characterized by higher basal levels of hepatic alpha-tocopherol and ascorbic
acid than that seen in the mouse.
PMID- 9653062
TI - Detection of the sarin hydrolysis product in formalin-fixed brain tissues of
victims of the Tokyo subway terrorist attack.
AB - One of the hydrolysis products of sarin (isopropyl methylphosphonofluoridate) was
detected in formalin-fixed brain tissues of victims poisoned in the Tokyo subway
terrorist attack. Part of this procedure, used for the detection of sarin
hydrolysis products in erythrocytes of sarin victims, has been described
previously. The test materials were four individual cerebellums, which had been
stored in formalin fixative for about 2 years. Sarin-bound acetylcholinesterase
(AChE) was solubilized from these cerebellums, purified by immunoaffinity
chromatography, and digested with trypsin. Then the sarin hydrolysis products
bound to AChE were released by alkaline phosphatase digestion, subjected to
trimethylsilyl derivatization (TMS), and detected by gas chromatography-mass
spectrometry. Peaks at m/z 225 and m/z 240, which are indicative of TMS
methylphosphonic acid, were observed within the retention time range of authentic
methylphosphonic acid. However, no isopropyl methylphosphonic acid was detected
in the formalin-fixed cerebellums of these 4 sarin victims, probably because the
isopropoxy group of isopropyl methylphosphonic acid underwent chemical hydrolysis
during storage. This procedure will be useful for the forensic diagnosis of
poisoning by protein-bound, highly toxic agents, such as sarin, which are easily
hydrolysed. This appears to be the first time that intoxication by a nerve agent
has been demonstrated by analyzing formalin-fixed brains obtained at autopsy.
PMID- 9653063
TI - Pharmacological profile of CEB-1957 and atropine toward brain muscarinic
receptors and comparative study of their efficacy against sarin poisoning.
AB - This study consists of two parts, first to compare the pharmacological profile of
atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various
rat brain structures, binding properties were determined by competition
experiments of [3H]pirenzepine, [3H]AF-DX 384, and [3H]4-DAMP in quantitative
autoradiography of M1, M2, and M3 muscarinic receptor subtypes, respectively.
Competition curves have shown that atropine presents similar nanomolar inhibition
constants toward each subtype, while CEB-1957 has distinct affinities (Ki from
0.26 to 73 nM) with the following range order: M3 > or = M2 > M1. The second part
is to compare atropine and CEB-1957 (in combination with pralidoxime) for their
ability to protect against the lethality induced by 2 x LD50 of the
acetylcholinesterase inhibitor sarin. CEB-1957 reduced the mortality at doses 10
times lower than atropine. Finally, from these results, it is proposed that a
selective blockade of M2 and M3 receptor subtypes could play a pivotal role in
the protective effect against sarin poisoning.
PMID- 9653064
TI - Inhalation of diesel exhaust enhances allergen-related eosinophil recruitment and
airway hyperresponsiveness in mice.
AB - We have previously shown that intratracheal instillation of suspension of diesel
exhaust particles enhances allergen-related eosinophilic airway inflammation,
airway hyperresponsiveness, and local expression of interleukin (IL)-5 and
granulocyte macrophage-colony stimulating factor (GM-CSF) in mice. The present
study was designed to elucidate the effects of daily inhalation of diesel exhaust
(DE) on the allergen-related respiratory disease. ICR mice were exposed for 40
weeks to clean air or DE at a soot concentration of 0.3, 1.0, or 3.0 mg/m3 with
aerosol allergen challenges (1% ovalbumin in isotonic saline for 6 min) at 3-week
intervals during the last 24 weeks of exposures. Exposure to DE enhanced allergen
related eosinophil recruitment to the submucosal layers of the airways and to the
bronchoalveolar space, and increased protein levels of GM-CSF and IL-5 in the
lung in a dose-dependent manner compared to exposure to clean air. There were
strong correlations between the number of eosinophils in bronchoalveolar lavage
(BAL) fluid and IL-5 concentrations in BAL supernatants and lung tissue
supernatants. In addition, the increases in eosinophil recruitment and local
cytokine expression were accompanied by goblet cell proliferation in the
bronchial epithelium and airway hyperresponsiveness to inhaled acetylcholine. In
contrast, the control mice exposed for 40 weeks to clean air or DE at a soot
concentration of 0.3, 1.0, or 3.0 mg/m3 without allergen provocation showed no
eosinophil recruitment to the submucosal layers of the airways nor to the
bronchoalveolar space and few goblet cells in the bronchial epithelium. The
present study provides experimental evidence that daily inhalation of DE can
enhance allergen-related respiratory diseases such as allergic asthma. This
effect may be mediated by the enhanced local expression of IL-5 and GM-CSF.
Increased ambient levels of DE may be implicated in the increasing prevalence of
bronchial asthma in recent years.
PMID- 9653066
TI - A comparison of the electrophysiological effects of two organophosphates, mipafox
and ecothiopate, on mouse limb muscles.
AB - Adult male albino mice were given single subcutaneous injections of either
mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus
compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow
twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28
days after dosing, in vitro electrophysiological measurements were carried out in
the soleus and EDL. Action potentials and end-plate potentials were evoked at 30
Hz and recorded intracellularly from single muscle fibers. The amplitudes, time
course, and latencies of these potentials were measured and the variability
(jitter) of latencies was calculated. Recordings after mipafox were also made
with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox
(65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in
the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action
potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates
caused an increase in end-plate potential amplitudes in the soleus. Mipafox
caused an increase in prejunctional (end-plate potential) jitter at 28 days after
dosing in both muscles. A single dose of ecothiopate also caused an increase in
prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter
was different at different frequencies of stimulation. The results show that
there are electrophysiological changes in both muscles after administration of
organophosphorus compounds. The slow-twitch soleus appears more sensitive to
prejunctional changes caused by OPs than the fast-twitch EDL.
PMID- 9653065
TI - Lipid ozonation products activate phospholipases A2, C, and D.
AB - Ozone exposure, in vitro, has been shown to activate phospholipases A2 (PLA2), C
(PLC), and D (PLD) in airway epithelial cells. However, because of its high
reactivity, ozone cannot penetrate far into the air/lung tissue interface. It has
been proposed that ozone reacts with unsaturated fatty acids (UFA) in the
epithelial lining fluid (ELF) and cell membranes to generate a cascade of lipid
ozonation products (LOP) that mediate ozone-induced toxicity. To test this
hypothesis, we exposed cultured human bronchial epithelial cells (BEAS-2B) to LOP
(1-100 microM) produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3
phosphatidylcholine (POPC) and measured the activity of PLA2, PLC, and PLD. The
PLA2 isoform responsible for arachidonic acid release (AA) in stimulated cultures
was also characterized. Activation of PLA2, PLC, and PLD by three oxidants,
hydrogen peroxide (H2O2), tert-butyl hydroperoxide (t-BOOH) and 2,2'-azobis(2
amidinopropane)dihydrochloride (AAPH) also was measured and compared to that of
LOP. The derivatives of ozonized POPC at the sn-2 residue, 9-oxononanoyl (PC
ALD), 9-hydroxy-9-hydroperoxynonanoyl (PC-HHP), and 8-(-5-octyl-1,2,4-trioxolan-3
yl-) octanoyl (POPC-OZ) selectively activated PLA2 in a dose-dependent fashion.
Cytosolic PLA2 (cPLA2) measured in the cytosolic fraction of stimulated cell
lysates was found to be the predominant isoform responsible for AA release. PLC
activation was exclusively induced by the hydroxyhydroperoxide derivatives. PC
HHP and the 9-carbon hydroxyhydroperoxide (HHP-C9) increased PLC activity. PLD
activity also was induced by LOP generated from POPC. Incubation of cultures with
H2O2 alone did not stimulate PLC; however, in the presence of the aldehyde,
nonanal, a 62 +/- 2% increase in PLC activity was found, suggesting that the
increase in activity was due to the formation of the intermediate HHP-C9. t-BOOH,
and AAPH also failed to induce PLA2 activation, but did activate PLC, under
conditions of exposure identical to that of LOP. Only t-BOOH activated PLD. These
results suggest that biologically relevant concentrations of LOP activate PLA2,
PLC, and PLD in the airway epithelial cell, a primary target to ozone exposure.
The activation of these phospholipases may play a role in the development of lung
inflammation during ozone exposure.
PMID- 9653067
TI - Methanol-induced contraction of canine cerebral artery and its possible mechanism
of action.
AB - In the present report, we investigated the effects of methanol on canine basilar
cerebral arterial rings. Our data indicate that acute methanol exposure (5-675
mM) induces potent contractile responses of cerebral arteries in a concentration
dependent manner. Pharmacological antagonists, such as propranolol, phentolamine,
haloperidol, methysergide, naloxone, diphenhydramine, and cimetidine, did not
exert any effects on these methanol-induced contractions. Likewise, a potent
antagonist of cyclo-oxygenase, and subsequent synthesis of prostanoids (i.e.,
indomethacin), failed to exert any effect on methanol-induced contractions. No
differences in responsiveness to methanol in canine cerebral arteries were found
in vessel segments with or without endothelial cells. Removal of extracellular
Ca2+ ([Ca2+]o) partially attenuated methanol-induced contractions, while
withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated the contractions. In the
complete absence of [Ca2+]o, 10 mM caffeine and 400 mM methanol induced similar,
transient contractions followed by relaxation in K(+)-depolarized cerebral
vascular tissues. Methanol-induced contractions were, however, completely
abolished by pretreatment of tissue with 10 mM caffeine. Our results indicate
that (1) methanol causes contractile responses of cerebral arterial smooth muscle
(independent of amine, prostanoid, or opioid mediation; (2) in addition to a need
for [Ca2+]o, an intracellular release of Ca2+ is required for methanol-induced
contractions; and (3) Mg deficiency potentiates the contractile responses of
methanol on these brain vessels. The data presented in the study suggest that
methanol-induced contractions occur via an sarcoplasmic reticulum-releasable
store of [Ca2+]i; via mediation of either ryanodine-caffeine type receptors or a
caffeine-releasable intracellular store of CA2+.
PMID- 9653068
TI - Ortho-substituted polychlorinated biphenyls activate respiratory burst measured
as luminol-amplified chemoluminescence in human granulocytes.
AB - The effect of polychlorinated biphenyls (PCBs) on the activation of respiratory
burst measured as luminol-amplified chemoluminescence in human granulocytes is
elucidated here. Chemoluminescence was stimulated in a concentration-dependent
manner (ED50 approximately 10 microM) by ortho-substituted PCB congeners, while
meta- and para-substituted congeners had no significant effect. Two ortho
substituted PCB congeners were chosen for the mechanistic studies, namely
2,2',4,4'-TeCB and 2,2'-DCB, since they have been used in previous studies by
others. In the absence of extracellular calcium, the respiratory burst in
response to 2,2'-DCB and 2,2',4,4'-TeCB was reduced by 63% and 82%, respectively.
Bisindolylmaleimide, which inhibits protein kinase C, reduced activated
chemoluminescence by 2,2'-DCB, 2,2',4,4'-TeCB, N-formyl-methionyl-leucyl
phenylalanine, and phorbol 12-myristate 13-acetate. Neomycin, which inhibits
phospholipase C, had a slight, but significant, effect on the 2,2',4,4'-TeCB
activated chemoluminescence but had a more pronounced effect on the 2,2'-DCB
activated chemoluminescence. 2,2'-DCB and 2,2',4,4'-TeCB significantly increased
phospholipase D (PLD) activity measured as the amount of 14C-phosphatidylbutanol
formed. Ethanol (1%), a phospholipase D modulator, reduced the response to 2,2'
DCB and 2,2',4,4'-TeCB by 72% and 75%, respectively. Furthermore, wortmannin (25
nM), a phosphatidylinositol 3-kinase, and genistein, a more unspecific tyrosine
kinase inhibitor, reduced chemoluminescence in response to PCB. In conclusion,
our results indicate that PCB-activated chemoluminescence is dependent on the
Ca(2+)-dependent phospholipase D or phospholipase C, phosphatidylinositol 3
kinase, and protein kinase C activation prior to activation of the NADPH oxidase.
Defects in neutrophhil functions upon exposure to PCB may render a greater
susceptibility in the host to invading microorganisms or evoke inappropriate
inflammatory responses leading to tissue injury.
PMID- 9653069
TI - Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick
hepatocytes.
AB - In earlier studies, treatment with sodium arsenite was shown to decrease total
hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting
step in heme degradation to biliverdin, was considered responsible for the
decrease in CYP. Here we investigated the effect of sodium arsenite on induction
of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo
hepatocytes. When added simultaneously with inducer, arsenite inhibited
phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated
increases in CYP1A, as measured enzymatically and immunochemically. Near maximal
decreases were observed in these forms of CYP at a concentration of 2.5 microM
sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by
sodium arsenite were concomitant with increases in heme oxygenase. Sodium
arsenite was not toxic at concentrations as high as 10 microM, as indicated by
protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had
no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form
of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin
(SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenite
induced heme oxygenase. However, SnMeso did not alter the effect of arsenite to
prevent phenobarbital-mediated increases in CYP2H protein. SnMeso alone inhibited
phenobarbital-mediated increases in CYP2H. Inclusion of 2 or 5 microM exogenous
heme with arsenite did not prevent the arsenite-mediated decrease in CYP2H.
Combined treatment with heme and phenobarbital induced heme oxygenase to the same
extent as treatment with heme, arsenite, and phenobarbital. However, CYP2H
activity was decreased only when the treatment included arsenite. These results
suggest that elevated levels of heme oxygenase alone are not responsible for
arsenite-mediated decreases in CYP2H.
PMID- 9653070
TI - Reproductive toxicity and tissue concentrations of low doses of 2,3,7,8
tetrachlorodibenzo-p-dioxin in male offspring rats exposed throughout pregnancy
and lactation.
AB - The effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the
reproductive system of male offspring rats were examined. The dams were treated
subcutaneously 2 weeks prior to mating and throughout mating, pregnancy, and
lactation. They received an initial loading dose of 25, 60, or 300 ng TCDD/kg
body wt, followed by a weekly maintenance dose of 5, 12, or 60 ng TCCD/kg body wt
(TCDD 25/5, TCDD 60/12, and TCDD 300/60). Three dams per group were killed on
Gestation Day 21 and the fetuses were removed. The concentration of TCDD in the
maternal liver and fat was measured. After birth, developmental landmarks in male
rats were monitored. At weaning, the concentration of TCDD in the offspring liver
and testis was determined. Effects on male reproduction were studied on Postnatal
Days (PND) 70 and 170. At weaning, the concentration of TCDD in the offspring
liver was 0.24, 0.39, and 1.78 ng/g in the TCDD 25/5, TCDD 60/12, and TCDD 300/60
groups, respectively. In the testes, the concentration of TCDD was 0.25 ng/g in
the TCDD 25/5 and TCDD 60/12 groups and 0.28 ng/g in the TCDD 300/60 group. The
number of sperm per cauda epididymis was reduced in TCDD groups at puberty and at
adulthood. Daily sperm production was permanently decreased as was the sperm
transit rate in the TCDD-exposed male rats, thus increasing the time required by
the sperm to pass through the cauda epididymis. Moreover, the male rats of the
TCDD groups showed an increased number of abnormal sperm when investigated at
adulthood. Similarly, mounting and intromission latencies were significantly
increased in the TCDD 25/5 and TCDD 300/60 groups. In the highest dose group,
serum testosterone concentration was decreased at adulthood. Likewise, in this
dose group permanent changes including pyknotic nuclei and the occurrence of cell
debris in the lumen were revealed. The lowest adverse effect level and the no
observed effect level can be estimated to be substantially lower than the
estimated daily dose of the lowest dose which is 0.8 ng/kg body wt/day. Sperm
parameters were more susceptible than the other end points investigated. However,
the question as to whether such doses exposed throughout gestation and lactation
induce subtle changes in humans remains to be determined.
PMID- 9653071
TI - Effect of a dopamine agonist on luteinizing hormone receptors, cyclic AMP
production and steroidogenesis in rat Leydig cells.
AB - Dopamine agonists are known to increase the incidence of Leydig cell
hyperplasia/adenomas when administered to rats over periods of 1-2 years. We have
examined the early changes in factors affecting luteinizing hormone (LH)
controlled signal transduction pathways and steroidogenesis in Leydig cells in
vitro after chronic oral administration of one of these dopamine agonists,
Mesulergine (CU327-085) (N-(1-6,dimethylergolin-8a-yl)-N',N'-dimethylsulphamide
hydrochloride) to Sprague-Dawley (SD) rats. Eight-week-old rats were given this
dopamine agonist (2 mg/kg body wt/day) in food for 1, 5, or 12 weeks. The Leydig
cells from control and treated rats were purified by elutriation and density
gradient centrifugation. The dopamine agonist treatment was found to decrease the
specific binding of 125I-human chorionic gonadotrophin (hCG) binding to the
Leydig cells: a decrease was detected as early as 1 week after treatment and was
more pronounced after 5 and 12 weeks. This was found to be due to a decrease in
the LH/hCG receptor numbers and not to a decrease in LH/hCG-receptor binding
affinity. Both basal and LH-stimulated cAMP and testosterone production were also
decreased; cAMP production was decreased by approximately 50% by all
concentrations of LH added whereas testosterone production was only decreased
with submaximum stimulating concentrations of LH. The formation of testosterone
in response to dibutyryl cAMP was also decreased by approximately 50%, indicating
additional lesions in the signal transduction pathway. The addition of the cell
permeant 22R-hydroxycholesterol (22R) demonstrated that testosterone but not
pregnenolone production was decreased by treatment with the dopamine agonist,
thus indicating that the 17 alpha-hydroxylase/C17-20 lyase may have been
inhibited. Supporting evidence for this was found because the dopamine agonist
also increased aromatase activity in the Leydig cells and thus the potential to
produce estrogens; previous studies have shown that estradiol is an inhibitor of
the 17-20 lyase enzyme. The addition of the dopamine agonist directly to the
Leydig cells did not inhibit cAMP production or testosterone production except at
high concentrations. It is concluded that treatment of rats with the dopamine
agonist indirectly (i.e., via the pituitary) affects Leydig cell function
resulting in a rapid decrease in LH receptors and cAMP and testosterone
production. Aromatase activity is increased and thus the capacity to produce
estrogens. These early changes in the signal transduction pathways and
steroidogenesis may be involved in the Leydig cell hyperplasia/adenoma formation
that subsequently occurs.
PMID- 9653072
TI - Urinary physiologic and chemical metabolic effects on the urothelial cytotoxicity
and potential DNA adducts of o-phenylphenol in male rats.
AB - ortho-Phenylphenol (OPP), a fungicide and antibacterial agent with food residues,
is carcinogenic to rat bladder. The present studies provide information on
changes in urinary composition and urinary metabolites, urothelial cytotoxicity
and regenerative hyperplasia, and DNA adducts in male F344 rats fed OPP. An
initial experiment evaluated dietary doses of 0, 1,000, 4,000, and 12,500 ppm OPP
fed for 13 weeks. There was no evidence of urinary calculi, microcrystalluria, or
calcium phosphate-containing precipitate, but urothelial cytotoxicity and
hyperplasia occurred at the highest dose only. In a second experiment, rats were
fed dietary OPP levels of 0, 800, 4,000, 8,000, and 12,500 ppm. Urinary pH was >
7 in all groups. Urinary volume was increased at the 2 highest doses with
consequent decreases in osmolality, creatinine, and other solutes. Total urinary
OPP metabolite excretions were increased, mostly excreted as conjugates of OPP
and of phenylhydroquinone. Free OPP or free metabolites accounted for less than
2% excreted in the urine without a dose response. Urothelial toxicity and
hyperplasia occurred only at doses of 8,000 and 12,500 ppm. OPP-DNA adducts were
not detected in the urothelium at any dose. In summary, OPP produces cytotoxicity
and proliferation of the urothelium at dietary doses > or = 8,000 ppm without
formation of urinary solids. The paucity of unconjugated metabolites and the lack
of OPP-DNA adducts suggests that OPP is acting as a bladder carcinogen in male
rats by inducing cytotoxicity and hyperplasia without it or its metabolites
directly binding to DNA.
PMID- 9653073
TI - A minimally toxic dose of methylene dianiline injures biliary epithelial cells in
rats.
AB - The threshold for hepatotoxicity and cholestasis induced by methylene dianiline
(DAPM) in rats is between 25 and 75 mg/kg (Bailie et al., Environ. Health
Perspect., 124, 25-30, 1993). Our objectives were to determine if a minimally
toxic dose of DAPM provided a model system for studies of selective injury to
biliary epithelial cells (BEC) in vivo. Thus, we examined the effects of 50 mg
DAPM/kg on (1) biliary constituents, (2) liver constituents likely involved in
DAPM biotransformation/detoxification, and (3) early morphological and
histochemical changes in the liver. Male Sprague Dawley rats had biliary cannulas
positioned under pentobarbital anesthesia. After 1 h of control bile collection,
rats received 50 mg DAPM/kg po in 35% ethanol or 35% ethanol only. Bile was
collected for another 6 h. Histochemical, ultrastructural, and biochemical liver
alterations were assessed at 3 h or at 3 and 6 h. DAPM had minimal effects on
biliary bile salt and bilirubin excretion over 6 h. Biliary glucose and protein
excretion were increased approximately 2-fold starting in Hour 1, while inorganic
phosphate excretion was not increased until Hour 2. Biliary glutathione excretion
initially increased (Hour 1) but then declined steadily for 5 h. Microsomal
cytochrome P-450 activities were transiently decreased at 3 h but had returned to
control values by 6 h. Liver glutathione (GSH and GSSG) was not affected by DAPM
at 3 or 6 h. Necrosis of intrahepatic bile ducts was severe at 6 h with moderate
injury in smaller bile ducts. Ultrastructural alterations were observed in BEC
mitochondria and microvilli at 3 h with no apparent alterations in hepatocyte
mitochondria or tight junctions between cells. In addition, histochemical
staining of liver sections and assays of mitochondrial enzyme activities in vitro
at 3 h revealed no loss of mitochondrial function in hepatocytes. These results
provide strong evidence for defining DAPM as a selective bile duct toxicant.
PMID- 9653074
TI - Treatment of rats during pubertal development with 2,3,7,8-tetrachlorodibenzo-p
dioxin alters both signaling kinase activities and epidermal growth factor
receptor binding in the testis and the motility and acrosomal reaction of sperm.
AB - Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10
micrograms/kg body wt) were administered i.p. to 21-day-old male Sprague-Dawley
rats. Control animals received the same volume of the vehicle (acetone:corn oil,
1:19). Body weight and daily food intake were recorded during the 90-day time
course of the study. Random samples of five rats were sacrificed at 34, 49, 62,
and 90 days of age. Epidermal growth factor receptor (EGFR) in whole testis was
measured, as were the activities of c-Src kinase, protein tyrosine kinase (PTK),
mitogen-activated protein 2 kinase (MAP2K also termed as Erk2), protein kinase A
(PKA), and protein kinase C (PKC). Testicular tissue from 90-day-old rats was
evaluated for histopathology, and sperm numbers in whole testis were counted to
estimate daily sperm production. The motility of sperm in the vas deferens and
caudal segments of the epididymis of 90-day-old rats was measured by computer
assisted sperm analysis (CASA) and the function of the sperm was tested by
assessment of acrosome reactions. A dose of 10 micrograms/kg resulted in
testicular atrophy and histopathologic examination revealed a decrease in the
diameter of the seminiferous tubules. Sertoli cell nuclei were clearly seen, but
the spermatogonial population was totally absent. Lower doses of TCDD did not
affect testicular histology, but doses as low as 1 microgram/kg significantly
decreased testicular sperm numbers and affected some sperm functions (motility
parameters and acrosome reactions) in 90-day-old rats. Significant decreases in
EGFR were found in 34-day-old rats and this effect on EGFR was sustained until
the end of the experiment (90 days). Although TCDD significantly increased c-Src
kinase activity in immature and mature rats, opposite effects of TCDD on
activities of PTK, PKA, and PKC were found in 34-day-old rats vs 49-, 62-, and 90
day-old rats. When 10 micrograms TCDD/kg was administered to 21-day-old rat, 24-h
after c-Src kinase inhibitor geldanamycin, there was no testicular atrophy and no
change in the daily sperm production was found. These findings provide evidence
for involvement of Src kinase signaling and EGFR in the mechanism by which TCDD
disrupts testicular development and subsequently affects testis function.
PMID- 9653077
TI - Chemical Index for Volume 150
AB - Copyright
PMID- 9653075
TI - Chemical-induced hepatocyte ploidy.
PMID- 9653078
TI - Medullary thymic epithelium: a mosaic of epithelial "self"?
PMID- 9653079
TI - CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is
mediated by medullary thymic epithelium.
AB - Inducible serum proteins whose concentrations oscillate between nontolerogenic
and tolerogenic levels pose a particular challenge to the maintenance of self
tolerance. Temporal restrictions of intrathymic antigen supply should prevent
continuous central tolerization of T cells, in analogy to the spatial limitation
imposed by tissue-restricted antigen expression. Major acute-phase proteins such
as human C-reactive protein (hCRP) are typical examples for such inducible self
antigens. The circulating concentration of hCRP, which is secreted by
hepatocytes, is induced up to 1,000-fold during an acute-phase reaction. We have
analyzed tolerance to hCRP expressed in transgenic mice under its autologous
regulatory regions. Physiological regulation of basal levels (<10(-9) M) and
inducibility (>500-fold) are preserved in female transgenics, whereas male
transgenics constitutively display induced levels. Surprisingly, crossing of hCRP
transgenic mice to two lines of T cell receptor transgenic mice (specific for
either a dominant or a subdominant epitope) showed that tolerance is mediated by
intrathymic deletion of immature thymocytes, irrespective of widely differing
serum levels. In the absence of induction, hCRP expressed by thymic medullary
epithelial cells rather than liver-derived hCRP is necessary and sufficient to
induce tolerance. Importantly, medullary epithelial cells also express two
homologous mouse acute-phase proteins. These results support a physiological role
of "ectopic" thymic expression in tolerance induction to acute-phase proteins and
possibly other inducible self-antigens and have implications for delineating the
relative contributions of central versus peripheral tolerance.
PMID- 9653080
TI - Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion
molecule.
AB - Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein
whose cell surface expression is induced under inflammatory conditions. It has
been shown previously to participate in lymphocyte recirculation by mediating the
binding of lymphocytes to peripheral lymph node vascular endothelial cells in an
L-selectin-independent fashion. We report here that the VAP-1 cDNA encodes a type
II transmembrane protein of 84.6 kD with a single transmembrane domain located at
the NH2-terminal end of the molecule and six potential N-glycosylation sites in
the extracellular domain. In vivo, the protein exists predominantly as a
homodimer of 170-180 kD. Ax endothelial cells transfected with a VAP-1 cDNA
express VAP-1 on their cell surface and bind lymphocytes, and the binding can be
partially inhibited with anti-VAP-1 mAbs. VAP-1 has no similarity to any
currently known adhesion molecules, but has significant identity to the copper
containing amine oxidase family and has a monoamine oxidase activity. We propose
that VAP-1 is a novel type of adhesion molecule with dual function. With the
appropriate glycosylation and in the correct inflammatory setting, its expression
on the lumenal endothelial cell surface allows it to mediate lymphocyte adhesion
and to function as an adhesion receptor involved in lymphocyte recirculation. Its
primary function in other locations where it is expressed, such as smooth muscle,
may depend on its inherent monoamine oxidase activity.
PMID- 9653081
TI - Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces
autoantibody production and renal immunoglobulin deposition.
AB - Anti-double-stranded DNA (dsDNA) antibodies are the serologic abnormality
characteristically associated with systemic lupus erythematosus (SLE) and may
play an important role in disease pathogenesis. Although the anti-dsDNA
antibodies present in SLE are indicative of an antigen-driven response, the
antigen has not been conclusively identified. By screening a phage peptide
display library, we demonstrated previously that the decapeptide DWEYSVWLSN is
specifically bound by the pathogenic murine IgG2b anti-dsDNA antibody R4A. To
investigate the possibility that a protein antigen might trigger lupus-like
autoimmunity, we immunized BALB/c mice with DWEYSVWLSN in adjuvant. Mice
developed significant titers of IgG anti-dsDNA antibodies 2-3 wk after the
initial immunization. Immunized mice also developed antibodies against some other
lupus autoantigens, and immunoglobulin deposition was present in renal glomeruli
at 49 d. Although an immune response to peptide and dsDNA was evident in BALB/c
mice, there was little response in other inbred strains. This study demonstrates
that lupus-like anti-dsDNA reactivity can be generated in nonautoimmune mice by
immunization with a peptide antigen. Peptide-induced autoimmunity may prove
useful in understanding the spreading of antigenic specificities targeted in SLE.
However, most importantly, the demonstration that a peptide antigen can initiate
a SLE-like immune response opens a new chapter on the potential antigenic stimuli
that might trigger SLE.
PMID- 9653082
TI - Transforming growth factor beta production is inversely correlated with severity
of murine malaria infection.
AB - We have examined the role of the immunomodulatory cytokine transforming growth
factor (TGF)-beta in the resolution and pathology of malaria in BALB/c mice.
Circulating levels of TGF-beta, and production of bioactive TGF-beta by
splenocytes, were found to be low in lethal infections with Plasmodium berghei.
In contrast, resolving infections with P. chabaudi chabaudi or P. yoelii were
accompanied by significant TGF-beta production. A causal association between the
failure to produce TGF-beta and the severity of malaria infection was
demonstrated by treatment of infected mice with neutralizing antibody to TGF
beta, which exacerbated the virulence of P. berghei and transformed a resolving
P. chabaudi chabaudi infection into a lethal infection, but had little effect on
the course of P. yoelii infection. Parasitemia increased more rapidly in anti-TGF
beta-treated mice but this did not seem to be the explanation for the increased
pathology of infection as peak parasitemias were unchanged. Treatment of P.
berghei-infected mice with recombinant TGF-beta (rTGF-beta) slowed the rate of
parasite proliferation and prolonged their survival from 15 to up to 35 d. rTGF
beta treatment was accompanied by a significant decrease in serum tumor necrosis
factor alpha and an increase in interleukin 10. Finally, we present evidence that
differences in TGF-beta responses in different malaria infections are due to
intrinsic differences between species of malaria parasites in their ability to
induce production of TGF-beta. Thus, TGF-beta seems to induce protective immune
responses, leading to slower parasite growth, early in infection, and,
subsequently, appears to downregulate pathogenic responses late in infection.
This duality of effect makes TGF-beta a prime candidate for a major
immunomodulatory cytokine associated with successful control of malaria
infection.
PMID- 9653083
TI - Phase-variable expression of lipopolysaccharide contributes to the virulence of
legionella pneumophila.
AB - With the aid of monoclonal antibody (mAb) 2625, raised against the
lipopolysaccharide (LPS) of Legionella pneumophila serogroup 1, subgroup OLDA, we
isolated mutant 811 from the virulent wild-type strain RC1. This mutant was not
reactive with mAb 2625 and exhibited an unstable phenotype, since we observed an
in vitro and in vivo switch of mutant 811 to the mAb 2625-positive phenotype,
thus restoring the wild-type LPS. Bactericidal assays revealed that mutant 811
was lysed by serum complement components, whereas the parental strain RC1 was
almost serum resistant. Moreover, mutant 811 was not able to replicate
intracellularly in macrophage-like cell line HL-60. In the guinea pig animal
model, mutant 811 exhibited significantly reduced ability to replicate. Among
recovered bacteria, mAb 2625-positive revertants were increased by fourfold. The
relevance of LPS phase switch for pathogenesis of Legionella infection was
further corroborated by the observation that 5% of the bacteria recovered from
the lungs of guinea pigs infected with the wild-type strain RC1 were negative for
mAb 2625 binding. These findings strongly indicate that under in vivo conditions
switching between two LPS phenotypes occurs and may promote adaptation and
replication of L. pneumophila. This is the first description of phase-variable
expression of Legionella LPS.
PMID- 9653084
TI - Evolution of a complex T cell receptor repertoire during primary and recall
bacterial infection.
AB - The mechanisms underlying the genesis and maintenance of T cell memory remain
unclear. In this study, we examined the evolution of a complex, antigen-specific
T cell population during the transition from primary effector to memory T cells
after Listeria monocytogenes infection. T cell populations specific for
listeriolysin O (LLO)91-99, the immunodominant epitope recognized by H2-Kd
restricted T lymphocytes, were directly identified in immune spleens using
tetrameric H2-Kd-epitope complexes. The T cell receptor (TCR) Vbeta repertoire of
specific T cells was determined by direct, ex vivo staining with a panel of mAbs.
We demonstrate that LLO91-99-specific, primary effector T cell populations have a
diverse TCR Vbeta repertoire. Analyses of memory T cell populations demonstrated
similar TCR diversity. Furthermore, experiments with individual mice demonstrated
that primary effector and memory T cells have indistinguishable TCR repertoires.
Remarkably, after reinfection with L. monocytogenes, LLO91-99-specific T cells
have a narrower TCR repertoire than do primary effector or memory T cells. Thus,
our studies show that the TCR repertoire of primary effector T lymphocytes is
uniformly transmitted to memory T cells, whereas expansion of memory T cells is
selective.
PMID- 9653085
TI - Conserved T cell receptor repertoire in primary and memory CD8 T cell responses
to an acute viral infection.
AB - Viral infections often induce potent CD8 T cell responses that play a key role in
antiviral immunity. After viral clearance, the vast majority of the expanded CD8
T cells undergo apoptosis, leaving behind a stable number of memory cells. The
relationship between the CD8 T cells that clear the acute viral infection and the
long-lived CD8 memory pool remaining in the individual is not fully understood.
To address this issue, we examined the T cell receptor (TCR) repertoire of virus
specific CD8 T cells in the mouse model of infection with lymphocytic
choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative
TCR beta chain V segment and complementarity determining region 3 (CDR3) length
repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV
specific CD8 T cells with MHC class I tetramers containing viral peptide and
costaining with TCR Vbeta-specific antibodies; and (c) functional TCR
fingerprinting based on recognition of variant peptides. We compared the
repertoire of CD8 T cells responding to acute primary and secondary LCMV
infections, together with that of virus-specific memory T cells in immune mice.
Our analysis showed that CD8 T cells from several Vbeta families participated in
the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL)
epitope (NP118-126). However, the bulk (approximately 70%) of this CTL response
was due to three privileged T cell populations systematically expanding during
LCMV infection. Approximately 30% of the response consisted of Vbeta10+ CD8 T
cells with a beta chain CDR3 length of nine amino acids, and 40% consisted of
Vbeta8.1+ (beta CDR3 = eight amino acids) and Vbeta8.2+ cells (beta CDR3 = six
amino acids). Finally, we showed that the TCR repertoire of the primary antiviral
CD8 T cell response was similar both structurally and functionally to that of the
memory pool and the secondary CD8 T cell effectors. These results suggest a
stochastic selection of memory cells from the pool of CD8 T cells activated
during primary infection.
PMID- 9653086
TI - Induction of HIV-1 replication in latently infected CD4+ T cells using a
combination of cytokines.
AB - Although it has been demonstrated that certain cytokines, particularly
proinflammatory cytokines, can enhance ongoing viral replication in peripheral
blood mononuclear cells (PBMCs) of HIV-1-infected individuals, it is unclear what
role these cytokines play in the induction of HIV-1 replication in latently
infected, resting CD4(+) T cells. This study demonstrates that the in vitro
combination of the proinflammatory cytokines interleukin (IL)-6 and tumor
necrosis factor (TNF)-alpha together with the immunoregulatory cytokine IL-2 are
potent inducers of viral replication in highly purified, latently infected,
resting CD4+ T cells derived from HIV-infected individuals who are antiretroviral
therapy-naive as well as those who are receiving highly active antiretroviral
therapy (HAART). Viral replication induced by this combination of cytokines was
completely suppressed in the presence of HAART in vitro. Given that an array of
cytokines, including IL-6, TNF-alpha, and IL-2, are copiously expressed in the
microenvironment of the lymphoid tissues, which harbor the latent viral
reservoirs, induction of HIV by this combination of cytokines may in part explain
the commonly observed reappearance of detectable plasma viremia in HIV-infected
individuals in whom HAART was discontinued. Moreover, since it is likely that
these infected cells die upon activation of virus and that HAART prevents spread
of virus to adjacent cells, the observation that this combination of cytokines
can markedly induce viral replication in this reservoir may have important
implications for the activation-mediated diminution of the latent reservoir of
HIV in patients receiving HAART.
PMID- 9653087
TI - The molecular mechanism of B cell activation by toll-like receptor protein RP
105.
AB - The B cell-specific transmembrane protein RP-105 belongs to the family of
Drosophila toll-like proteins which are likely to trigger innate immune responses
in mice and man. Here we demonstrate that the Src-family protein tyrosine kinase
Lyn, protein kinase C beta I/II (PKCbetaI/II), and Erk2-specific mitogen
activated protein (MAP) kinase kinase (MEK) are essential and probably
functionally connected elements of the RP-105-mediated signaling cascade in B
cells. We also find that negative regulation of RP-105-mediated activation of MAP
kinases by membrane immunoglobulin may account for the phenomenon of antigen
receptor-mediated arrest of RP-105-mediated B cell proliferation.
PMID- 9653088
TI - Distinct methylation of the interferon gamma (IFN-gamma) and interleukin 3 (IL-3)
genes in newly activated primary CD8+ T lymphocytes: regional IFN-gamma promoter
demethylation and mRNA expression are heritable in CD44(high)CD8+ T cells.
AB - Differential genomic DNA methylation has the potential to influence the
development of T cell cytokine production profiles. Therefore, we have conducted
a clonal analysis of interferon (IFN)-gamma and interleukin (IL)-3 gene
methylation and messenger (m)RNA expression in primary CD8+ T cells during the
early stages of activation, growth, and cytokine expression. Despite similar
distributions and densities of CpG methylation sites, the IFN-gamma and IL-3
promoters exhibited differential demethylation in the same T cell clone, and
heterogeneity between clones. Methylation patterns and mRNA levels were
correlated for both genes, but demethylation of the IFN-gamma promoter was
widespread across >300 basepairs in clones expressing high levels of IFN-gamma
mRNA, whereas demethylation of the IL-3 promoter was confined to specific CpG
sites in the same clones. Conversely, the majority of clones expressing low or
undetectable levels of IFN-gamma mRNA exhibited symmetrical methylation of four
to six of the IFN-gamma promoter CpG sites. Genomic DNA methylation also has the
potential to influence the maintenance or stability of T cell cytokine production
profiles. Therefore, we also tested the heritability of IFN-gamma gene
methylation and mRNA expression in families of clones derived from resting
CD44(low)CD8+ T cells or from previously activated CD44(high)CD8+ T cells. The
patterns of IFN-gamma gene demethylation and mRNA expression were faithfully
inherited in all clones derived from CD44(high) cells, but variable in clones
derived from CD44(low) cells. Overall, these findings suggest that differential
genomic DNA methylation, including differences among cytokine genes, among
individual T cells, and among T cells with different activation histories, is an
important feature of cytokine gene expression in primary T cells.
PMID- 9653089
TI - Spontaneous skin ulceration and defective T cell function in CD18 null mice.
AB - A null mutation was prepared in the mouse for CD18, the beta2 subunit of
leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with
extensive facial and submandibular erosions. The phenotype includes elevated
neutrophil counts, increased immunoglobulin levels, lymphadenopathy,
splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney.
Very few neutrophils were found in spontaneously occurring skin lesions or with
an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a
lack of firm neutrophil attachment to venules in the cremaster muscle in response
to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell
proliferation was found in the CD18 null mice when T cell receptors were
stimulated either by staphylococcal enterotoxin A or by major histocompatibility
complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T
cell responses than previously documented. The null mice are useful for
delineating the functions of CD18 in vivo.
PMID- 9653090
TI - Interferon gamma-independent rejection of interleukin 12-transduced carcinoma
cells requires CD4+ T cells and Granulocyte/Macrophage colony-stimulating factor.
AB - We analyzed the ability of interferon (IFN)-gamma knockout mice (GKO) to reject a
colon carcinoma transduced with interleukin (IL)-12 genes (C26/IL-12). Although
the absence of IFN-gamma impaired the early response and reduced the time to
tumor onset in GKO mice, the overall tumor take rate was similar to that of
BALB/c mice. In GKO mice, C26/IL-12 tumors had a reduced number of infiltrating
leukocytes, especially CD8 and natural killer cells. Analysis of the tumor site,
draining nodes, and spleens of GKO mice revealed reduced expression of IFN-
inducible protein 10 and monokine induced by gamma-IFN. Despite these defects,
GKO mice that rejected C26/IL-12 tumor, and mice that were primed in vivo with
irradiated C26/IL-12 cells, showed the same cytotoxic T lymphocyte activity but
higher production of granulocyte/macrophage colony-stimulating factor (GM-CSF) as
compared with control BALB/c mice. Treatment with monoclonal antibodies against
GM-CSF abrogated tumor regression in GKO but not in BALB/c mice. CD4 T
lymphocytes, which proved unnecessary or suppressive during rejection of C26/IL
12 cells in BALB/c mice, were required for tumor rejection in GKO mice. CD4 T
cell depletion was coupled with a decline in GM-CSF expression by lymphocytes
infiltrating the tumors or in the draining nodes, and with the reduction and
disappearance of granulocytes and CD8 T cells, respectively, in tumor nodules.
These results suggest that GM-CSF can substitute for IFN-gamma in maintaining the
CD8-polymorphonuclear leukocyte cross-talk that is a hallmark of tumor rejection.
PMID- 9653091
TI - Antiviral protection and germinal center formation, but impaired B cell memory in
the absence of CD19.
AB - Coligation of CD19, a molecule expressed during all stages of B cell development
except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a
factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as
possible phosphorylation sites and is postulated to function as the signal
transducing element for complement receptor (CR)2. Generation and analysis of
CD19 gene-targeted mice revealed that T cell-dependent (TD) antibody responses to
proteinaceous antigens were impaired, whereas those to T cell-independent (TI)
type 2 antigens were normal or even augmented. These results are compatible with
earlier complement depletion studies and the postulated function of CD19. To
analyze the role of CD19 in antiviral antibody responses, we immunized CD19(-/-)
mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI
responses was more dependent on antigen dose and replicative capacity than on
antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal
transducer for complement. In contrast to immunization with protein antigens,
infection of CD19(-/-) mice with replicating virus led to generation of specific
germinal centers, which persisted for >100 d, whereas maintenance of memory
antibody titers as well as circulating memory B cells was fully dependent on
CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under
limiting antigen conditions and indicates an important role for B cell memory.
PMID- 9653092
TI - The coordinated action of CC chemokines in the lung orchestrates allergic
inflammation and airway hyperresponsiveness.
AB - The complex pathophysiology of lung allergic inflammation and bronchial
hyperresponsiveness (BHR) that characterize asthma is achieved by the regulated
accumulation and activation of different leukocyte subsets in the lung. The
development and maintenance of these processes correlate with the coordinated
production of chemokines. Here, we have assessed the role that different
chemokines play in lung allergic inflammation and BHR by blocking their
activities in vivo. Our results show that blockage of each one of these
chemokines reduces both lung leukocyte infiltration and BHR in a substantially
different way. Thus, eotaxin neutralization reduces specifically BHR and lung
eosinophilia transiently after each antigen exposure. Monocyte chemoattractant
protein (MCP)-5 neutralization abolishes BHR not by affecting the accumulation of
inflammatory leukocytes in the airways, but rather by altering the trafficking of
the eosinophils and other leukocytes through the lung interstitium.
Neutralization of RANTES (regulated upon activation, normal T cell expressed and
secreted) receptor(s) with a receptor antagonist decreases significantly
lymphocyte and eosinophil infiltration as well as mRNA expression of eotaxin and
RANTES. In contrast, neutralization of one of the ligands for RANTES receptors,
macrophage-inflammatory protein 1alpha, reduces only slightly lung eosinophilia
and BHR. Finally, MCP-1 neutralization diminishes drastically BHR and
inflammation, and this correlates with a pronounced decrease in monocyte- and
lymphocyte-derived inflammatory mediators. These results suggest that different
chemokines activate different cellular and molecular pathways that in a
coordinated fashion contribute to the complex pathophysiology of asthma, and that
their individual blockage results in intervention at different levels of these
processes.
PMID- 9653093
TI - B lymphocytes producing demyelinating autoantibodies: development and function in
gene-targeted transgenic mice.
AB - We studied the cellular basis of self tolerance of B cells specific for brain
autoantigens using transgenic mice engineered to produce high titers of
autoantibodies against the myelin oligodendrocyte glycoprotein (MOG), a surface
component of central nervous system myelin. We generated "knock-in" mice by
replacing the germline JH locus with the rearranged immunoglobulin (Ig) H chain
variable (V) gene of a pathogenic MOG-specific monoclonal antibody. In the
transgenic mice, conventional B cells reach normal numbers in bone marrow and
periphery and express exclusively transgenic H chains, resulting in high titers
of MOG-specific serum Igs. Additionally, about one third of transgenic B cells
bind MOG, thus demonstrating the absence of active tolerization. Furthermore,
peritoneal B-1 lymphocytes are strongly depleted. Upon immunization with MOG, the
mature transgenic B cell population undergoes normal differentiation to plasma
cells secreting MOG-specific IgG antibodies, during which both Ig isotype
switching and somatic mutation occur. In naive transgenic mice, the presence of
this substantial autoreactive B cell population is benign, and the mice fail to
develop either spontaneous neurological disease or pathological evidence of
demyelination. However, the presence of the transgene both accelerates and
exacerbates experimental autoimmune encephalitis, irrespective of the identity of
the initial autoimmune insult.
PMID- 9653094
TI - Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic
cells in lymphoid tissues and strongly attracts naive T cells and activated B
cells.
AB - Movement of T and B lymphocytes through secondary lymphoid tissues is likely to
involve multiple cues that help the cells navigate to appropriate compartments.
Epstein-Barr virus- induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3beta) is
expressed constitutively within lymphoid tissues and may act as such a guidance
cue. Here, we have isolated mouse ELC and characterized its expression pattern
and chemotactic properties. ELC is expressed constitutively in dendritic cells
within the T cell zone of secondary lymphoid tissues. Recombinant ELC was
strongly chemotactic for naive (L-selectinhi) CD4 T cells and for CD8 T cells and
weakly attractive for resting B cells and memory (L-selectinlo) CD4 T cells.
After activation through the B cell receptor, the chemotactic response of B cells
was enhanced. Like its human counterpart, murine ELC stimulated cells transfected
with EBI-1/CC chemokine receptor 7 (CCR7). Our findings suggest a central role
for ELC in promoting encounters between recirculating T cells and dendritic cells
and in the migration of activated B cells into the T zone of secondary lymphoid
tissues.
PMID- 9653095
TI - In vivo inhibition of CC and CX3C chemokine-induced leukocyte infiltration and
attenuation of glomerulonephritis in Wistar-Kyoto (WKY) rats by vMIP-II.
AB - Chemokines play a central role in immune and inflammatory responses. It has been
observed recently that certain viruses have evolved molecular piracy and mimicry
mechanisms by encoding and synthesizing proteins that interfere with the normal
host defense response. One such viral protein, vMIP-II, encoded by human
herpesvirus 8, has been identified with in vitro antagonistic activities against
CC and CXC chemokine receptors. We report here that vMIP-II has additional
antagonistic activity against CX3CR1, the receptor for fractalkine. To
investigate the potential therapeutic effect of this broad-spectrum chemokine
antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of
experimental glomerulonephritis induced by an antiglomerular basement membrane
antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-,
macrophage inflammatory protein 1beta-, RANTES (regulated on activation, normal T
cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated
leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte
infiltration to the glomeruli, and markedly attenuated proteinuria. These results
suggest that molecules encoded by some viruses may serve as useful templates for
the development of antiinflammatory compounds.
PMID- 9653096
TI - Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection
of cardiac allografts in CD28-deficient mice: CTLA4 can function independently of
CD28.
AB - Cytotoxic T lymphocyte antigen 4 (CTLA4) appears to negatively regulate T cell
activation. One mechanism by which CTLA4 might antagonize T cell function is
through inhibition of CD28 signaling by competing for their shared ligands B7-1
and B7-2. In addition, CTLA4 ligation could initiate a signaling cascade that
inhibits T cell activation. To address whether CTLA4 could inhibit immune
responses in the absence of CD28, rejection of heart allografts was studied in
CD28-deficient mice. H-2(q) hearts were transplanted into allogeneic wild-type or
CD28-deficient mice (H-2(b)). Graft rejection was delayed in CD28-deficient
compared with wild-type mice. Treatment of wild-type recipients with CTLA4
immunoglobulin (Ig), or with anti-B7-1 plus anti-B7-2 mAbs significantly
prolonged allograft survival. In contrast, treatment of CD28-deficient mice with
CTLA4-Ig, anti-B7-1 plus anti-B7-2 mAbs, or a blocking anti-CTLA4 mAb induced
acceleration of allograft rejection. This increased rate of graft rejection was
associated with more severe mononuclear cell infiltration and enhanced levels of
IFN-gamma and IL-6 transcripts in donor hearts of untreated wild-type and CTLA4
Ig- or anti-CTLA4 mAb-treated CD28-deficient mice. Thus, the negative regulatory
role of CTLA4 extends beyond its potential ability to prevent CD28 activation
through ligand competition. Even in the absence of CD28, CTLA4 plays an
inhibitory role in the regulation of allograft rejection.
PMID- 9653097
TI - B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in
the absence of CD28.
AB - Ligation of cytotoxic T lymphocyte antigen 4 (CTLA4) appears to inhibit T cell
responses. Four mechanisms have been proposed to explain the inhibitory activity
of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of
signaling molecules away from CD28 via endocytosis; delivery of a signal that
antagonizes a CD28 signal; and delivery of a signal that antagonizes a T cell
receptor (TCR) signal. As three of these potential mechanisms involve functional
antagonism of CD28, an experimental model was designed to determine whether CTLA4
could inhibit T cell function in the absence of CD28. TCR transgenic/recombinase
activating gene 2-deficient/CD28-wild-type or CD28-deficient mice were generated
and immunized with an antigen-expressing tumor. Primed T cells from both types of
mice produced cytokines and proliferated in response to stimulator cells lacking
B7 expression. However, whereas the response of CD28+/+ T cells was augmented by
costimulation with B7-1, the response of the CD28-/- T cells was strongly
inhibited. This inhibition was reversed by monoclonal antibody against B7-1 or
CTLA4. Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28,
indicating that antagonism of a TCR-mediated signal is sufficient to explain the
inhibitory effect of CTLA4.
PMID- 9653098
TI - Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression
protects endothelial cells from tumor necrosis factor alpha-induced apoptosis.
AB - By differential screening of tumor necrosis factor alpha (TNF-alpha) and
lipopolysaccharide (LPS)- activated endothelial cells (ECs), we have identified a
cDNA clone that turned out to be a member of the inhibitor of apoptosis (iap)
gene family. iap genes function to protect cells from undergoing apoptotic death
in response to a variety of stimuli. These iap genes, hiap1, hiap2, and xiap were
found to be strongly upregulated upon treatment of ECs with the inflammatory
cytokines TNF-alpha, interleukin 1beta, and LPS, reagents that lead to activation
of the nuclear transcription factor kappaB (NF-kappaB). Indeed, overexpression of
IkappaBalpha, an inhibitor of NF-kappaB, suppresses the induced expression of iap
genes and sensitizes ECs to TNF-alpha-induced apoptosis. Ectopic expression of
one member of the human iap genes, human X-chromosome-linked iap (xiap), using
recombinant adenovirus overrules the IkappaBalpha effect and protects ECs from
TNF-alpha- induced apoptosis. We conclude that xiap represents one of the NF
kappaB-regulated genes that counteracts the apoptotic signals caused by TNF-alpha
and thereby prevents ECs from undergoing apoptosis during inflammation.
PMID- 9653099
TI - Reversal of proinflammatory responses by ligating the macrophage Fcgamma receptor
type I.
AB - Macrophages can respond to a variety of infectious and/or inflammatory stimuli by
secreting an array of proinflammatory cytokines, the overproduction of which can
result in shock or even death. In this report, we demonstrate that ligation of
macrophage Fcgamma receptors (FcgammaR) can lead to a reversal of macrophage
proinflammatory responses by inducing an upregulation of interleukin (IL)-10,
with a reciprocal inhibition of IL-12 production. IL-10 upregulation was specific
to FcgammaR ligation, since the ligation of the Mac-1 receptor did not alter IL
10 production. The identification of the specific FcgammaR subtype responsible
for IL-10 upregulation was determined in gene knockout mice. Macrophages from
mice lacking the FcR gamma chain, which is required for assembly and signaling by
FcgammaRI and FcgammaRIII, failed to upregulate IL-10 in response to immune
complexes. However, mice lacking either the FcgammaRII or the FcgammaRIII were
fully capable of upregulating IL-10 production, implicating FcgammaRI in this
process. The biological consequences of FcgammaRI ligation were determined in
both in vitro and in vivo models of inflammation and sepsis. In all of the models
tested, the ligation of FcgammaR promoted the production of IL-10 and inhibited
the secretion of IL-12. This reciprocal alteration in the pattern of macrophage
cytokine production illustrates a potentially important role for FcgammaR
mediated clearance in suppressing macrophage proinflammatory responses.
PMID- 9653100
TI - Chloride channels and endocytosis: ClC-5 makes a dent.
PMID- 9653101
TI - An infectious origin of extraskeletal calcification.
PMID- 9653102
TI - A new twist on protein crystallization.
PMID- 9653103
TI - The instability of stratified flows at large Richardson numbers.
AB - In contrast to conventional expectations based on the stability of steady shear
flows, elementary time-periodic stratified flows that are unstable at arbitrarily
large Richardson numbers are presented here. The fundamental instability is a
parametric one with twice the period of the basic state. This instability
spontaneously generates local shears on buoyancy time scales near a specific
angle of inclination that saturates into a localized regime of strong mixing with
density overturning. We speculate that such instabilities may contribute
significantly to the step-like microstructure often observed in buoyancy
measurements in the ocean.
PMID- 9653104
TI - Stable relativistic/charge-displacement channels in ultrahigh power density
(approximately 10(21 W/cm3) plasmas.
AB - Robust stability is a chief characteristic of relativistic/charge-displacement
self-channeling. Theoretical analysis of the dynamics of this stability (i)
reveals a leading role for the eigenmodes in the development of stable channels,
(ii) suggests a technique using a simple longitudinal gradient in the electron
density to extend the zone of stability into the high electron density/high power
density regime, (iii) indicates that a situation approaching unconditional
stability can be achieved, (iv) demonstrates the efficacy of the stable dynamics
in trapping severely perturbed beams in single uniform channels, and (v) predicts
that approximately 10(4) critical powers can be trapped in a single stable
channel. The scaling of the maximum power density with the propagating wavelength
lambda is shown to be proportional to lambda-4 for a given propagating power and
a fixed ratio of the electron plasma density to the critical plasma density. An
estimate of the maximum power density that can be achieved in these channels with
a power of approximately 2 TW at a UV (248 nm) wavelength gives a value of
approximately 10(21) W/cm3 with a corresponding atomic specific magnitude of
approximately 60 W/atom. The characteristic intensity propagating in the channel
under these conditions exceeds 10(21) W/cm2.
PMID- 9653105
TI - Genes from mycoparasitic fungi as a source for improving plant resistance to
fungal pathogens.
AB - Disease resistance in transgenic plants has been improved, for the first time, by
the insertion of a gene from a biocontrol fungus. The gene encoding a strongly
antifungal endochitinase from the mycoparasitic fungus Trichoderma harzianum was
transferred to tobacco and potato. High expression levels of the fungal gene were
obtained in different plant tissues, which had no visible effect on plant growth
and development. Substantial differences in endochitinase activity were detected
among transformants. Selected transgenic lines were highly tolerant or completely
resistant to the foliar pathogens Alternaria alternata, A. solani, Botrytis
cinerea, and the soilborne pathogen Rhizoctonia solani. The high level and the
broad spectrum of resistance obtained with a single chitinase gene from
Trichoderma overcome the limited efficacy of transgenic expression in plants of
chitinase genes from plants and bacteria. These results demonstrate a rich source
of genes from biocontrol fungi that can be used to control diseases in plants.
PMID- 9653106
TI - An adenoviral vector deleted for all viral coding sequences results in enhanced
safety and extended expression of a leptin transgene.
AB - Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part
by cellular immune responses to viral-encoded proteins and/or transgene
immunogenicity. In an attempt to diminish the former responses, we have
previously developed and described helper-dependent (HD) Ad vectors in which the
viral protein coding sequences are completely eliminated. These HD vectors have
up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based
system, and can be produced to high concentration and purity (>99.9% helper-free
vector). In this study, we compared safety and efficacy of leptin gene delivery
mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector
(Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to
evidence of liver toxicity, inflammation, and cellular infiltration observed with
Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant
improvement in associated safety/toxicity and resulted in efficient gene
delivery, prolonged elevation of serum leptin levels, and associated weight loss.
The greater safety, efficient gene delivery, and increased insert capacity of HD
vectors are significant improvements over current Ad vectors and represent
favorable features especially for clinical gene therapy applications.
PMID- 9653107
TI - Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn
superoxide dismutase.
AB - Transfection of V79 Chinese hamster cells produced clones in which CuZn
superoxide dismutase (CuZn-SOD) activities were 2.2- to 3. 5-fold higher than in
the parental cells. An overall reduction of antioxidant enzyme activities and
both total and oxidized glutathione levels had been found in these clones.
Aconitase activities in these cells were determined to indirectly measure the O2-
steady-state levels. As expected, in cells overexpressing CuZn-SOD, both total
and cytosolic aconitase activities have increased. Because these clones showed
reduced oxidized glutathione contents, it is unlikely that they present higher
H2O2 steady-state levels as a consequence of the higher SOD levels. This was
confirmed by measuring H2O2 steady-state levels in cells by flow cytometric
analysis of 2',7'-dichlorofluorescein diacetate-treated cells. Despite the
decreased antioxidant defenses, three of the clones overexpressing CuZn-SOD
showed reduced H2O2 steady-state levels. These reduced H2O2 steady-state levels
were found even when the cells were treated with the O2- generator 2,3-dimethoxy
1, 4-naphthoquinone. These data provide in vivo support for the hypothesis
proposed by Liochev and Fridovich [Liochev, S. I. & Fridovich, I. (1994) Free
Radical Biol. Med. 16, 29-33] that O2- dismutation prevents the formation of
higher H2O2 levels by other reactions.
PMID- 9653108
TI - Structural similarities between topoisomerases that cleave one or both DNA
strands.
AB - Type IA and type II DNA topoisomerases are distinguished by their ability to
cleave one or two strands, respectively, of a DNA duplex. Both types have been
proposed to use an "enzyme-bridging" mechanism, in which a break is formed in a
DNA strand and a gap is opened between the broken pieces to allow passage of a
second DNA strand or duplex segment. Although the type IA and type II
topoisomerase structures appear overall quite different from one another,
unexpected similarities between several structural elements suggest that members
of the two subfamilies may use comparable mechanisms to bind and cleave DNA.
PMID- 9653109
TI - Control of interferon-tau gene expression by Ets-2.
AB - Expression of the multiple interferon-tau (IFN-tau) genes is restricted to
embryonic trophectoderm of ruminant ungulate species for a few days in early
pregnancy. The promoter regions of these genes are highly conserved. A proximal
(bp -91 to -69) sequence has been implicated in controlling trophoblast-specific
expression. Here it was used as a target for yeast one-hybrid screening of a day
13 conceptus cDNA library. Two transcription factors of the Ets family, Ets-2 and
GABPalpha, were identified, consistent with the observation that active ovine IFN
tau genes contain a single 10-bp Ets motif (core: GGAA) in the proximal segment,
whereas three known inactive ovine genes contain a mutated core motif (TGAA).
Cotransfection of a promoter- (-126 to +50) luciferase reporter construct from an
active gene (bovineIFN-tau1; boIFNT1) and an Ets-2 expression plasmid in human
JAr cells provided up to a 30-fold increase in reporter expression, whereas
promoters from inactive genes were not transactivated. GABPalpha alone was
ineffective and had only a approximately 2-fold positive effect when coexpressed
with its partner GABPbeta. Other Ets-related transcription factors, which were
not detected in the genetic screen, also provided a range of lesser
transactivation effects. Coexpression of Ets-2 and activated Ras failed to
transactivate the IFNT promoter greater than Ets-2 alone in JAr cells. The
presence of Ets-2 in nuclei of embryonic trophectoderm was confirmed
immunocytochemically. Together, these data suggest that Ets-2 plays a role in the
transient expression of the nonvirally inducible IFNT genes.
PMID- 9653110
TI - Mammalian Golgi apparatus UDP-N-acetylglucosamine transporter: molecular cloning
by phenotypic correction of a yeast mutant.
AB - Transporters in the Golgi apparatus membrane translocate nucleotide sugars from
the cytosol into the Golgi lumen before these can be substrates for the
glycosylation of proteins, lipids, and proteoglycans. We have cloned the
mammalian Golgi membrane transporter for uridine diphosphate-N-acetylglucosamine
by phenotypic correction with cDNA from MDCK cells of a recently characterized
Kluyveromyces lactis mutant deficient in Golgi transport of the above nucleotide
sugar. Phenotypically corrected transformants were separated from mutants in a
fluorescent-activated cell sorter after labeling of K. lactis cells with
fluorescein isothiocyanate (FITC) conjugated to Griffonia simplicifolia II
lectin, which binds terminal N-acetylglucosamine. A 2-kb DNA fragment was found
to restore the wild-type cell lectin binding phenotype, which reverted to the
mutant one upon loss of the plasmid. The DNA fragment contained an ORF encoding a
hydrophobic, multitransmembrane spanning protein of 326 aa that had only 22%
amino acid sequence identity with the corresponding transporter from K. lactis
but showed 53% amino acid sequence identity to the mammalian UDP-galactose
transporters and 40% to the CMP-sialic acid transporter. Golgi vesicles from the
transformant regained their ability to transport UDP-GlcNAc in an assay in vitro.
The above results demonstrate that the mammalian Golgi UDP-GlcNAc transporter
gene has all of the necessary information for the protein to be expressed and
targeted functionally to the Golgi apparatus of yeast and that two proteins with
very different amino acid sequences may transport the same solute within the same
Golgi membrane.
PMID- 9653111
TI - Structural, functional, and evolutionary relationships between lambda-exonuclease
and the type II restriction endonucleases.
AB - lambda-exonuclease participates in DNA recombination and repair. It binds a free
end of double-stranded DNA and degrades one strand in the 5' to 3' direction. The
primary sequence does not appear to be related to any other protein, but the
crystal structure shows part of lambda-exonuclease to be similar to the type II
restriction endonucleases PvuII and EcoRV. There is also a weaker correspondence
with EcoRI, BamHI, and Cfr10I. The structure comparisons not only suggest that
these enzymes all share a similar catalytic mechanism and a common structural
ancestor but also provide strong evidence that the toroidal structure of lambda
exonuclease encircles its DNA substrate during hydrolysis.
PMID- 9653112
TI - The mouse and human genes encoding the recognition component of the N-end rule
pathway.
AB - The N-end rule relates the in vivo half-life of a protein to the identity of its
N-terminal residue. The N-end rule pathway is one proteolytic pathway of the
ubiquitin system. The recognition component of this pathway, called N-recognin or
E3, binds to a destabilizing N-terminal residue of a substrate protein and
participates in the formation of a substrate-linked multiubiquitin chain. We
report the cloning of the mouse and human Ubr1 cDNAs and genes that encode a
mammalian N-recognin called E3alpha. Mouse UBR1p (E3alpha) is a 1,757-residue
(200-kDa) protein that contains regions of sequence similarity to the 225-kDa
Ubr1p of the yeast Saccharomyces cerevisiae. Mouse and human UBR1p have apparent
homologs in other eukaryotes as well, thus defining a distinct family of
proteins, the UBR family. The residues essential for substrate recognition by the
yeast Ubr1p are conserved in the mouse UBR1p. The regions of similarity among the
UBR family members include a putative zinc finger and RING-H2 finger, another
zinc-binding domain. Ubr1 is located in the middle of mouse chromosome 2 and in
the syntenic 15q15-q21.1 region of human chromosome 15. Mouse Ubr1 spans
approximately 120 kilobases of genomic DNA and contains approximately 50 exons.
Ubr1 is ubiquitously expressed in adults, with skeletal muscle and heart being
the sites of highest expression. In mouse embryos, the Ubr1 expression is highest
in the branchial arches and in the tail and limb buds. The cloning of Ubr1 makes
possible the construction of Ubr1-lacking mouse strains, a prerequisite for the
functional understanding of the mammalian N-end rule pathway.
PMID- 9653113
TI - PRT1 of Arabidopsis thaliana encodes a component of the plant N-end rule pathway.
AB - Mutants in the PRT1 gene of Arabidopsis thaliana are impaired in the degradation
of a normally short-lived intracellular protein that contains a destabilizing N
terminal residue. Proteins bearing such residues are the substrates of an
ubiquitin-dependent proteolytic system called the N-end rule pathway. The
chromosomal position of PRT1 was determined, and the PRT1 gene was isolated by
map-based cloning. The 45-kDa PRT1 protein contains two RING finger domains and
one ZZ domain. No other proteins in databases match these characteristics of
PRT1. There is, however, a weak similarity to Rad18p of Saccharomyces cerevisiae.
The RING finger domains have been found in a number of other proteins that are
involved in ubiquitin conjugation, consistent with the proposed role of PRT1 in
the plant N-end rule pathway.
PMID- 9653114
TI - Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with
the GTPase ADP ribosylation factor 1.
AB - Cytohesin-1 (B2-1) is a guanine nucleotide exchange factor for human ADP
ribosylation factor (Arf) GTPases, which are important for vesicular protein
trafficking and coatamer assembly in the cell. Cytohesin-1 also has been reported
to promote cellular adhesion via binding to the beta2 integrin cytoplasmic
domain. The solution structure of the Sec7 domain of cytohesin-1, which is
responsible for both the protein's guanine nucleotide exchange factor function
and beta2 integrin binding, was determined by NMR spectroscopy. The structure
consists of 10 alpha-helices that form a unique tertiary fold. The binding
between the Sec7 domain and a soluble, truncated version of human Arf-1 was
investigated by examining 1H-15N and 1H-13C chemical shift changes between the
native protein and the Sec7/Arf-1 complex. We show that the binding to Arf-1
occurs through a large surface on the C-terminal subdomain that is composed of
both hydrophobic and polar residues. Structure-based mutational analysis of the
cytohesin-1 Sec7 domain has been used to identify residues important for binding
to Arf and for mediating nucleotide exchange. Investigations into the interaction
between the Sec7 domain and the beta2 integrin cytoplasmic domain suggest that
the two proteins do not interact in the solution phase.
PMID- 9653116
TI - Arabinogalactan-proteins from Nicotiana alata and Pyrus communis contain
glycosylphosphatidylinositol membrane anchors.
AB - Arabinogalactan-proteins (AGPs) are a class of proteoglycans found in cell
secretions and plasma membranes of plants. Attention is currently focused on
their structure and their potential role in growth and development. We present
evidence that two members of a major class of AGPs, the classical AGPs, AGPNa1
from styles of Nicotiana alata and AGPPc1 from cell suspension cultures of Pyrus
communis, undergo C-terminal processing involving glycosylphosphatidylinositol
membrane anchors. The evidence is that (i) the transmembrane helix at the C
terminus predicted from the cDNA encoding these proteins is not present-the C
terminal amino acid is Asn87 and Ser97 for AGPNa1 and AGPPc1, respectively; (ii)
both AGP protein backbones are substituted with ethanolamine at the C-terminal
amino acid; and (iii) inositol, glucosamine, and mannose are present in the
native AGPs. An examination of the deduced amino acid sequences of other
classical AGP protein backbones shows that glycosylphosphatidylinositol-anchors
may be a common feature of this class of AGPs.
PMID- 9653115
TI - Molecular basis of cooperative DNA bending and oriented heterodimer binding in
the NFAT1-Fos-Jun-ARRE2 complex.
AB - Cooperative DNA binding by transcription factors that bind to separate
recognition sites is likely to require bending of intervening sequences and the
appropriate orientation of transcription factor binding. We investigated DNA
bending in complexes formed by the basic region-leucine zipper domains of Fos and
Jun with the DNA binding region of nuclear factor of activated T cells 1 (NFAT1)
at composite regulatory elements using gel electrophoretic phasing analysis. The
NFAT1-Fos-Jun complex induced a bend at the ARRE2 site that was distinct from the
sum of the bends induced by NFAT1 and Fos-Jun separately. We designate this
difference DNA bending cooperativity. The bending cooperativity was directed
toward the interaction interface between Fos-Jun and NFAT1. We also examined the
influence of NFAT1 on the orientation of Fos-Jun heterodimer binding using a
novel fluorescence resonance energy transfer assay. The interaction with NFAT1
could reverse the orientation of Fos-Jun heterodimer binding to the ARRE2 site.
The principal determinants of both cooperative DNA bending and oriented
heterodimer binding were localized to three amino acid residues at the amino
terminal ends of the leucine zippers of Fos and Jun. Consequently, interactions
between transcription factors can remodel promoters by altering DNA bending and
the orientation of heterodimer binding.
PMID- 9653117
TI - The tyrosine kinase regulator Cbl enhances the ubiquitination and degradation of
the platelet-derived growth factor receptor alpha.
AB - The Cbl protooncogene product has emerged as a negative regulator of receptor and
nonreceptor tyrosine kinases. We recently demonstrated that oncogenic Cbl mutants
upregulate the endogenous tyrosine kinase signaling machinery when expressed in
the NIH 3T3 cells, and identified the platelet-derived growth factor receptor
alpha (PDGFRalpha) as one of the tyrosine kinases targeted by these oncogenes.
These findings suggested a role for the normal Cbl protein in negative regulation
of the PDGFRalpha. However, the mechanism of such negative regulation remained to
be determined. Here we show that overexpression of the wild-type Cbl enhances the
ligand-induced ubiquitination of the PDGFRalpha. Concomitantly, the PDGFRalpha in
Cbl-overexpressing cells undergoes a faster ligand-induced degradation compared
with that in the control cells. These results identify a role for Cbl in the
regulation of ligand-induced ubiquitination and degradation of receptor tyrosine
kinases and suggest one potential mechanism for evolutionarily conserved negative
regulatory influence of Cbl on tyrosine kinases.
PMID- 9653118
TI - The stability of the RNA bases: implications for the origin of life.
AB - High-temperature origin-of-life theories require that the components of the first
genetic material are stable. We therefore have measured the half-lives for the
decomposition of the nucleobases. They have been found to be short on the
geologic time scale. At 100 degreesC, the growth temperatures of the
hyperthermophiles, the half-lives are too short to allow for the adequate
accumulation of these compounds (t1/2 for A and G approximately 1 yr; U = 12 yr;
C = 19 days). Therefore, unless the origin of life took place extremely rapidly
(<100 yr), we conclude that a high-temperature origin of life may be possible,
but it cannot involve adenine, uracil, guanine, or cytosine. The rates of
hydrolysis at 100 degreesC also suggest that an ocean-boiling asteroid impact
would reset the prebiotic clock, requiring prebiotic synthetic processes to begin
again. At 0 degreesC, A, U, G, and T appear to be sufficiently stable (t1/2 >/=
10(6) yr) to be involved in a low-temperature origin of life. However, the lack
of stability of cytosine at 0 degreesC (t1/2 = 17, 000 yr) raises the possibility
that the GC base pair may not have been used in the first genetic material unless
life arose quickly (<10(6) yr) after a sterilization event. A two-letter code or
an alternative base pair may have been used instead.
PMID- 9653119
TI - The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP)
coactivator complex interacts directly with nuclear receptors in a ligand
dependent fashion.
AB - Cognate cDNAs are described for 2 of the 10 thyroid hormone receptor-associated
proteins (TRAPs) that are immunopurified with thyroid hormone receptor alpha
(TRalpha) from ligand-treated HeLa (alpha-2) cells. Both TRAP220 and TRAP100
contain LXXLL domains found in other nuclear receptor-interacting proteins and
both appear to reside in a single complex with other TRAPs (in the absence of
TR). However, only TRAP220 shows a direct ligand-dependent interaction with
TRalpha, and these interactions are mediated through the C terminus of TRalpha
and (at least in part) the LXXLL domains of TRAP220. TRAP220 also interacts with
other nuclear receptors [vitamin D receptor, retinoic acid receptor alpha,
retinoid X receptor alpha, peroxisome proliferation-activated receptor (PPAR)
alpha, PPARgamma and, to a lesser extent, estrogen receptor] in a ligand
dependent manner, whereas TRAP100 shows only marginal interactions with estrogen
receptor, retinoid X receptor alpha, PPARalpha, and PPARgamma. Consistent with
these results, TRAP220 moderately stimulates human TRalpha-mediated transcription
in transfected cells, whereas a fragment containing the LXXLL motifs acts as a
dominant negative inhibitor of nuclear receptor-mediated transcription both in
transfected cells (TRalpha) and in cell free transcription systems (TRalpha and
vitamin D receptor). These studies indicate that TRAP220 plays a major role in
anchoring other TRAPs to TRalpha during the function of the TRalpha-TRAP complex
and, further, that TRAP220 (possibly along with other TRAPs) may be a global
coactivator for the nuclear receptor superfamily.
PMID- 9653120
TI - Activity of the yeast MNN1 alpha-1,3-mannosyltransferase requires a motif
conserved in many other families of glycosyltransferases.
AB - A wide diversity of biological molecules are modified by the addition of sugar
residues, and a large number of glycosyltransferases have been identified that
are responsible for these reactions. Despite catalyzing closely related
reactions, many of these transferases show little apparent sequence homology. By
comparing two apparently unrelated families of yeast Golgi mannosyltransferases,
a short motif containing two aspartate residues was observed that was conserved
in both groups of proteins. Mutagenesis of one of the members of these families,
the alpha-1, 3-mannosyltransferase Mnn1p, showed that altering either of these
aspartates eliminates all enzymatic activity. These changes do not appear to
affect the overall folding and assembly of Mnn1p. A similar aspartate-containing
sequence was found to be conserved in a diverse range of other
glycosyltransferase families, much more frequently than would be expected by
chance, suggesting that it is a feature of the catalytic site, or an element of a
structural fold, shared by many glycosyltransferases.
PMID- 9653121
TI - Functional coupling between secretory phospholipase A2 and cyclooxygenase-2 and
its regulation by cytosolic group IV phospholipase A2.
AB - Secretory phospholipase A2 (sPLA2) is the major effector involved in arachidonic
acid (AA) mobilization and prostaglandin E2 (PGE2) production during stimulation
of P388D1 macrophages with the inflammatory stimuli bacterial lipopolysaccharide
and platelet-activating factor. We herein demonstrate that PGE2 in stimulated
P388D1 cells is accounted for by the inducible cyclooxygenase (COX)-2. COX-1,
though present, appears not to participate significantly in stimulus-induced PGE2
production in P388D1 macrophages. Reconstitution experiments utilizing exogenous
recombinant sPLA2 demonstrate that activation of the sPLA2 at the plasma membrane
is highly dependent on previous activation of the cytosolic phospholipase A2
(cPLA2). Collectively these results demonstrate (i) that functional coupling
exists between sPLA2 and COX-2 in activated cells, (ii) the critical role that
cPLA2 plays in lipid mediator production, and (iii) that there is crosstalk
between cPLA2 and sPLA2 in the cell.
PMID- 9653122
TI - An N-terminal fragment of the gene 4 helicase/primase of bacteriophage T7 retains
primase activity in the absence of helicase activity.
AB - Primase and helicase activities of bacteriophage T7 are present in a single
polypeptide coded by gene 4. Because the amino terminal region of the gene 4
protein contributes to primase activity, we constructed a truncated gene 4
encoding the N-terminal 271-aa residues. The truncated protein, purified from
cells overexpressing the protein, is a dimer in solution; the full-length protein
is a hexamer. Although the fragment is devoid of dTTPase and helicase activities,
it catalyzes template-directed synthesis of di-, tri-, and tetranucleotides. The
rates for tetraribonucleotide synthesis and for dinucleotide extension on a 20
nucleotide template are similar for the full-length and truncated proteins.
However, the activity of the primase fragment is unaffected by dTTP whereas the
primase activity of the full-length protein is stimulated >14-fold. The primase
fragment is defective in the interaction with T7 DNA polymerase in that primer
synthesis cannot be coupled to DNA synthesis.
PMID- 9653123
TI - Functional and molecular characterization of a glycosomal PPi-dependent enzyme in
trypanosomatids: pyruvate, phosphate dikinase.
AB - Trypanosomatids are parasitic protists that have an ATP-dependent glycolysis with
no indication of PPi-dependent metabolism. Most of the glycolysis takes place in
peroxisome-like organelles, the glycosomes. We characterized in Trypanosoma
brucei a single-copy gene encoding a PPi-dependent enzyme, pyruvate, phosphate
dikinase (PPDK), which was expressed functionally in Escherichia coli. Specific
antibodies detected a 100-kDa protein in procyclic forms but not in mammalian
forms of T. brucei, indicating a differential expression. Glycosomal localization
of PPDK was determined by immunofluorescence analysis and was confirmed by
Western blot analysis on glycosomal fractions by using anti-PPDK antibodies.
Expression and localization of recombinant PPDKs in procyclic forms of T. brucei
showed that the AKL motif at the C-terminal extremity of PPDK is necessary for
glycosomal targeting. PPDK was detected in every trypanosomatid tested
Trypanosoma congolense, Trypanosoma vivax, Trypanosoma cruzi, Phytomonas,
Crithidia and Leishmania-with a good correlation between amount of protein and
enzymatic activity. The precise role of PPDK in trypanosomatid carbohydrate
metabolism remains to be clarified.
PMID- 9653124
TI - The SbcCD nuclease of Escherichia coli is a structural maintenance of chromosomes
(SMC) family protein that cleaves hairpin DNA.
AB - Hairpin structures can inhibit DNA replication and are intermediates in certain
recombination reactions. We have shown that the purified SbcCD protein of
Escherichia coli cleaves a DNA hairpin. This cleavage does not require the
presence of a free (3' or 5') DNA end and generates products with 3'-hydroxyl and
5'-phosphate termini. Electron microscopy of SbcCD has revealed the "head-rod
tail" structure predicted for the SMC (structural maintenance of chromosomes)
family of proteins, of which SbcC is a member. This work provides evidence
consistent with the proposal that SbcCD cleaves hairpin structures that halt the
progress of the replication fork, allowing homologous recombination to restore
DNA replication.
PMID- 9653125
TI - Structural characterization and immunochemical detection of a fluorophore derived
from 4-hydroxy-2-nonenal and lysine.
AB - Aging and the progression of certain degenerative diseases are accompanied by
increases in intracellular fluorescent material, termed "lipofuscin" and ceroid,
respectively. These pigments are observed within granules composed, in part, of
damaged protein and lipid. Modification of various biomolecules by aldehyde
products of lipid peroxidation is believed to contribute to lipofuscin and ceroid
formation. However, little direct evidence currently exists because the
structures responsible for the fluorescent, cross-linked nature of this material
are not well characterized. In this study, we have identified a fluorescent
product formed in the reaction of Nalpha-acetyllysine and 4-hydroxy-2-nonenal
(HNE), a major product of lipid peroxidation and the most reactive of these
compounds under physiological conditions [Esterbauer, H., Shaur, R. J. & Zollner,
H. (1991) Free Radical Biol. Med. 11, 81-128]. This fluorescent compound,
characterized as a 2-hydroxy-3-imino-1,2-dihydropyrrol derivative, appears to
form upon oxidative cyclization of the nonfluorescent 2:1 lysine-HNE Michael
adduct-Schiff base cross-link. Polyclonal antibody was raised to the Nalpha
acetyllysine-HNE fluorophore and found to be highly specific to the chromophore
structure of the compound. This antibody has been used to conclusively
demonstrate that the lysine-HNE derivative of this fluorophore forms on protein
upon exposure to HNE. The results of this study therefore provide the basis for
future investigations on the contribution(s) of HNE-derived fluorophore formation
to lipofuscin and ceroid accumulation.
PMID- 9653126
TI - Localization of signal recognition particle RNA in the nucleolus of mammalian
cells.
AB - The signal recognition particle (SRP) of eukaryotic cells is a cytoplasmic
ribonucleoprotein machine that arrests the translational elongation of nascent
secretory and membrane proteins and facilitates their transport into the
endoplasmic reticulum. The spatial pathway of SRP RNA processing and
ribonucleoprotein assembly in the cell is not known. In the present
investigation, microinjection of fluorescently tagged SRP RNA into the nucleus of
mammalian cells was used to examine its intranuclear sites of localization.
Microinjection of SRP RNA into the nuclei of normal rat kidney (NRK) epithelial
cells maintained at 37 degreesC on the microscope stage resulted in a very rapid
initial localization in nucleoli, followed by a progressive decline of nucleolar
signal and an increase of fluorescence at discrete sites in the cytoplasm.
Nuclear microinjection of a molecule corresponding to a major portion of the Alu
domain of SRP RNA revealed a pattern of rapid nucleolar localization followed by
cytoplasmic appearance of signal that was similar to the results obtained with
full-length SRP RNA. In contrast, a molecule corresponding to the S domain of SRP
RNA did not display nucleolar localization to the extent observed with full
length SRP RNA. An SRP RNA molecule lacking helix 6 of the S domain displayed
normal nucleolar localization, whereas one lacking helix 8 of the S domain did
not. These results, obtained by direct, real-time observation of fluorescent RNA
molecules inside the nucleus of living mammalian cells, suggest that the
processing of SRP RNA or its ribonucleoprotein assembly into the SRP involves a
nucleolar phase.
PMID- 9653127
TI - Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent
degradation domain via the ubiquitin-proteasome pathway.
AB - Hypoxia induces a group of physiologically important genes such as erythropoietin
and vascular endothelial growth factor. These genes are transcriptionally up
regulated by hypoxia-inducible factor 1 (HIF-1), a global regulator that belongs
to the basic helix-loop-helix PAS family. Although HIF-1 is a heterodimer
composed of alpha and beta subunits, its activity is primarily determined by
hypoxia-induced stabilization of HIF-1alpha, which is otherwise rapidly degraded
in oxygenated cells. We report the identification of an oxygen-dependent
degradation (ODD) domain within HIF-1alpha that controls its degradation by the
ubiquitin-proteasome pathway. The ODD domain consists of approximately 200 amino
acid residues, located in the central region of HIF-1alpha. Because portions of
the domain independently confer degradation of HIF-1alpha, deletion of this
entire region is required to give rise to a stable HIF-1alpha, capable of
heterodimerization, DNA-binding, and transactivation in the absence of hypoxic
signaling. Conversely, the ODD domain alone confers oxygen-dependent instability
when fused to a stable protein, Gal4. Hence, the ODD domain plays a pivotal role
for regulating HIF-1 activity and thereby may provide a means of controlling gene
expression by changes in oxygen tension.
PMID- 9653128
TI - Gp91(phox) is the heme binding subunit of the superoxide-generating NADPH
oxidase.
AB - The phagocyte NADPH oxidase flavocytochrome b558 is a membrane-bound heterodimer
comprised of a glycosylated subunit, gp91(phox), and a nonglycosylated subunit,
p22(phox). It contains two nonidentical heme groups that mediate the final steps
of electron transfer to molecular oxygen (O2), resulting in the generation of
superoxide ion (O2-). However, the location of the hemes within the
flavocytochrome heterodimer remains controversial. In this study, we have used
transgenic COS7 cell lines expressing gp91(phox), p22(phox), or both polypeptides
to examine the relative role of each flavocytochrome b558 subunit in heme binding
and O2- formation. A similar membrane localization was observed when gp91(phox)
and p22(phox) were either expressed individually or coexpressed, as analyzed by
confocal microscopy and immunoblotting of subcellular fractions. Spectral
analysis of membranes prepared from COS7 cell lines expressing either gp91(phox)
or both gp91(phox) and p22(phox) showed a b-type cytochrome with spectral
characteristics identical to those of human neutrophil flavocytochrome b558. In
contrast, no heme spectrum was detected in wild-type COS7 membranes or those
containing only p22(phox). Furthermore, redox titration studies suggested that
two heme groups were contained in gp91(phox) expressed in COS7 membranes, with
midpoint potentials of -264 and -233 mV that were very similar to those obtained
for neutrophil flavocytochrome b558. These results provide strong support for the
hypothesis that gp91(phox) is the sole heme binding subunit of flavocytochrome
b558. However, coexpression of gp91(phox) and p22(phox) in COS7 membranes was
required to support O2- production in combination with neutrophil cytosol,
indicating that the functional assembly of the active NADPH oxidase complex
requires both subunits of flavocytochrome b558.
PMID- 9653129
TI - High level transactivation by a modified Bombyx ecdysone receptor in mammalian
cells without exogenous retinoid X receptor.
AB - Our studies of the Bombyx mori ecdysone receptor (BE) revealed that, unlike the
Drosophila melanogaster ecdysone receptor (DE), treatment of BE with the ecdysone
agonist tebufenozide stimulated high level transactivation in mammalian cells
without adding an exogenous heterodimer partner. Gel mobility shift and
transfection assays with both the ultraspiracle gene product (Usp) and retinoid X
receptor heterodimer partners indicated that this property of BE stems from
significantly augmented heterodimer complex formation and concomitant DNA
binding. We have mapped this "gain of function" to determinants within the D and
E domains of BE and demonstrated that, although the D domain determinant is
sufficient for high affinity heterodimerization with Usp, both determinants are
necessary for high affinity interaction with retinoid X receptor. Modified BE
receptors alone used as replication-defective retroviruses potently stimulated
separate "reporter" viruses in all cell types examined, suggesting that BE has
potentially broad utility in the modulation of transgene expression in mammalian
cells.
PMID- 9653130
TI - gp120 envelope glycoproteins of human immunodeficiency viruses competitively
antagonize signaling by coreceptors CXCR4 and CCR5.
AB - Signal transductions by the dual-function CXCR4 and CCR5 chemokine receptors/HIV
type 1 (HIV-1) coreceptors were electrophysiologically monitored in Xenopus
laevis oocytes that also coexpressed the viral receptor CD4 and a G protein
coupled inward-rectifying K+ channel (Kir 3.1). Large Kir 3.1-dependent currents
generated in response to the corresponding chemokines (SDF-1alpha for CXCR4 and
MIP-1alpha; MIP-1beta and RANTES for CCR5) were blocked by pertussis toxin,
suggesting involvement of inhibitory guanine nucleotide-binding proteins.
Prolonged exposures to chemokines caused substantial but incomplete
desensitization of responses with time constants of 5-7 min and recovery time
constants of 12-19 min. CXCR4 and CCR5 exhibited heterologous desensitization in
this oocyte system, suggesting possible inhibition of a common downstream step in
their signaling pathways. In contrast to chemokines, perfusion with monomeric or
oligomeric preparations of the glycoprotein of Mr 120, 000 (gp120) derived from
several isolates of HIV-1 did not activate signaling by CXCR4 or CCR5 regardless
of CD4 coexpression. However, adsorption of the gp120 from a T-cell-tropic virus
resulted in CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas
gp120 from macrophage-tropic viruses caused CD4-dependent antagonism of CCR5
response to MIP-1alpha. These antagonisms could be partially overcome by high
concentrations of chemokines and were specific for coreceptors of the
corresponding HIV-1 isolates, suggesting that they resulted from direct
interactions of gp120-CD4 complexes with coreceptors and that they did not
involve the desensitization pathway. These results indicate that monomeric or
oligomeric gp120s specifically antagonize CXCR4 and CCR5 signaling in response to
chemokines, but they do not exclude the possibility that gp120s might also
function as weak agonists in some cells. The gp120-mediated disruption of CXCR4
and CCR5 signaling may contribute to AIDS pathogenesis.
PMID- 9653131
TI - Reaching the global minimum in docking simulations: a Monte Carlo energy
minimization approach using Bezier splines.
AB - The docking problem faces two major challenges: the global optimization of a
multivariable function, such as the energy, and the ability to discriminate
between true and false positive results, i.e., native from nonnative structures
based on the input energy function. Among all energy evaluation tools, only a
local energy-minimization method using an accurate enough potential function is
able to discriminate between native and nonnative structures. To meet these
requirements, a Monte Carlo with energy-minimization method has been incorporated
into a new ECEPP/3 docking program. The efficiency of the simulation results from
the use of an energy-grid technique based on Bezier splines and from a
simplification of the receptor by switching on the energy of only important
residues of the active site. Simulations of a thrombin-inhibitor complex show
that the global minimum of the energy function was reached in every independent
run within less than 3 min of time on an IBM RX 6000 computer. For comparison, 10
standard independent Monte Carlo simulations with 10(6) steps in each were
carried out. Only three of them led to a conformation close to the x-ray
structure. The latter simulations required an average of 24 min and about 10 hr
with and without the grid, respectively. Another important result is that the
Bezier spline technique not only speeds up the calculation by reducing the number
of operations during the energy evaluation but also helps in reaching the global
minimum by smoothing out the potential energy surface.
PMID- 9653132
TI - Characterizing semilocal motions in proteins by NMR relaxation studies.
AB - The understanding of protein function is incomplete without the study of protein
dynamics. NMR spectroscopy is valuable for probing nanosecond and picosecond
dynamics via relaxation studies. The use of 15N relaxation to study backbone
dynamics has become virtually standard. Here, we propose to measure the
relaxation of additional nuclei on each peptide plane allowing for the
observation of anisotropic local motions. This allows the nature of local motions
to be characterized in proteins. As an example, semilocal rotational motion was
detected for part of a helix of the protein Escherichia coli flavodoxin.
PMID- 9653133
TI - Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase.
AB - Elucidating the structures of intermediates in the reduction of O2 to water by
cytochrome c oxidase is crucial to understanding both oxygen activation and
proton pumping by the enzyme. In the work here, the reaction of O2 with the mixed
valence enzyme, in which only heme a3 and CuB in the binuclear center are
reduced, has been followed by time-resolved resonance Raman spectroscopy. The
results show that O==O bond cleavage occurs within the first 200 micros after
reaction initiation; the presence of a uniquely stable Fe---O---O(H) peroxy
species is not detected. The product of this rapid reaction is a heme a3
oxoferryl (FeIV==O) species, which requires that an electron donor in addition to
heme a3 and CuB must be involved. The available evidence suggests that the
additional donor is an amino acid side chain. Recent crystallographic data
[Yoshikawa, S., Shinzawa-Itoh, K., Nakashima, R., Yaono, R., Yamashita, E.,
Inoue, N., Yao, M., Fei, M. J., Libeu, C. P., Mizushima, T., et al. Science, in
press; Ostermeier, C., Harrenga, A. , Ermler, U. & Michel, H. (1997) Proc. Natl.
Acad. Sci. USA 94, 10547-10553] show that one of the CuB ligands, His240, is
cross-linked to Tyr244 and that this cross-linked tyrosyl is ideally positioned
to participate in dioxygen activation. We propose a mechanism for O---O bond
cleavage that proceeds by concerted hydrogen atom transfer from the cross-linked
His---Tyr species to produce the product oxoferryl species, CuB2+---OH-, and the
tyrosyl radical. This mechanism provides molecular structures for two key
intermediates that drive the proton pump in oxidase; moreover, it has clear
analogies to the proposed O---O bond forming chemistry that occurs during O2
evolution in photosynthesis.
PMID- 9653134
TI - Inhibitor binding changes domain mobility in the iron-sulfur protein of the
mitochondrial bc1 complex from bovine heart.
AB - We have analyzed crystal structures of cytochrome bc1 complexes with electron
transfer inhibitors bound to the ubiquinone binding pockets Qi and/or Qo in the
cytochrome b subunit. The presence or absence of the Qi inhibitor antimycin A did
not affect the binding of the Qo inhibitors. Different subtypes of Qo inhibitors
had dramatically different effects on the mobility of the extramembrane domain of
the iron-sulfur protein (ISP): Binding of 5-undecyl-6-hydroxy-4, 7
dioxobenzothiazol and stigmatellin (subtype Qo-II and Qo-III, respectively) led
to a fixation of the ISP domain on the surface of cytochrome b, whereas binding
of myxothiazol and methoxyacrylate-stilbene (subtype Qo-I) favored release of
this domain. The native structure has an empty Qo pocket and is intermediate
between these extremes. On the basis of these observations we propose a model of
quinone oxidation in the bc1 complex, which incorporates fixed and loose states
of the ISP as features important for electron transfer and, possibly, also proton
transport.
PMID- 9653135
TI - Myosin conformational states determined by single fluorophore polarization.
AB - Muscle contraction is powered by the interaction of the molecular motor myosin
with actin. With new techniques for single molecule manipulation and fluorescence
detection, it is now possible to correlate, within the same molecule and in real
time, conformational states and mechanical function of myosin. A spot-confocal
microscope, capable of detecting single fluorophore polarization, was developed
to measure orientational states in the smooth muscle myosin light chain domain
during the process of motion generation. Fluorescently labeled turkey gizzard
smooth muscle myosin was prepared by removal of endogenous regulatory light chain
and re-addition of the light chain labeled at cysteine-108 with the 6-isomer of
iodoacetamidotetramethylrhodamine (6-IATR). Single myosin molecule fluorescence
polarization data, obtained in a motility assay, provide direct evidence that the
myosin light chain domain adopts at least two orientational states during the
cyclic interaction of myosin with actin, a randomly disordered state, most likely
associated with myosin whereas weakly bound to actin, and an ordered state in
which the light chain domain adopts a finite angular orientation whereas strongly
bound after the powerstroke.
PMID- 9653136
TI - Lipid nanotubes as substrates for helical crystallization of macromolecules.
AB - A general approach for crystallization of proteins in a fast and simple manner
would be of immense interest to biologists studying protein structure-function
relationships. Here, we describe a method that we have developed for promoting
the formation of helical arrays of proteins and macromolecular assemblies.
Electron micrographs of the arrays are suitable for helical image analysis and
three-dimensional reconstruction. We show that hydrated mixtures of the
glycolipid galactosylceramide (GalCer) and derivatized lipids or charged lipids
form unilamellar nanotubules. The tubules bind proteins in a specific manner via
high affinity ligands on the polar head groups of the lipid or via electrostatic
interactions. By doping the GalCer with a novel nickel-containing lipid, we have
been able to form helical arrays of two histidine-tagged proteins. Similarly,
doping with a biotinylated lipid allows crystallization of streptavidin. Finally,
three proteins with affinity for positively or negatively charged lipid layers
formed helical arrays on appropriately charged tubules. The generality of this
method may allow a wide variety of proteins to be crystallized on lipid nanotubes
under physiological conditions.
PMID- 9653137
TI - Automated high resolution optical mapping using arrayed, fluid-fixed DNA
molecules.
AB - New mapping approaches construct ordered restriction maps from fluorescence
microscope images of individual, endonuclease-digested DNA molecules. In optical
mapping, molecules are elongated and fixed onto derivatized glass surfaces,
preserving biochemical accessibility and fragment order after enzymatic
digestion. Measurements of relative fluorescence intensity and apparent length
determine the sizes of restriction fragments, enabling ordered map construction
without electrophoretic analysis. The optical mapping system reported here is
based on our physical characterization of an effect using fluid flows developed
within tiny, evaporating droplets to elongate and fix DNA molecules onto
derivatized surfaces. Such evaporation-driven molecular fixation produces well
elongated molecules accessible to restriction endonucleases, and notably, DNA
polymerase I. We then developed the robotic means to grid DNA spots in well
defined arrays that are digested and analyzed in parallel. To effectively harness
this effect for high-throughput genome mapping, we developed: (i) machine vision
and automatic image acquisition techniques to work with fixed, digested molecules
within gridded samples, and (ii) Bayesian inference approaches that are used to
analyze machine vision data, automatically producing high-resolution restriction
maps from images of individual DNA molecules. The aggregate significance of this
work is the development of an integrated system for mapping small insert clones
allowing biochemical data obtained from engineered ensembles of individual
molecules to be automatically accumulated and analyzed for map construction.
These approaches are sufficiently general for varied biochemical analyses of
individual molecules using statistically meaningful population sizes.
PMID- 9653138
TI - Nature of PEVK-titin elasticity in skeletal muscle.
AB - A unique sequence within the giant titin molecule, the PEVK domain, has been
suggested to greatly contribute to passive force development of relaxed skeletal
muscle during stretch. To explore the nature of PEVK elasticity, we used titin
specific antibodies to stain both ends of the PEVK region in rat psoas myofibrils
and determined the region's force-extension relation by combining
immunofluorescence and immunoelectron microscopy with isolated myofibril
mechanics. We then tried to fit the results with recent models of polymer
elasticity. The PEVK segment elongated substantially at sarcomere lengths above
2.4 micro(m) and reached its estimated contour length at approximately 3.5
micro(m). In immunofluorescently labeled sarcomeres stretched and released
repeatedly above 3 micro(m), reversible PEVK lengthening could be readily
visualized. At extensions near the contour length, the average force per titin
molecule was calculated to be approximately 45 pN. Attempts to fit the force
extension curve of the PEVK segment with a standard wormlike chain model of
entropic elasticity were successful only for low to moderate extensions. In
contrast, the experimental data also could be correctly fitted at high extensions
with a modified wormlike chain model that incorporates enthalpic elasticity.
Enthalpic contributions are likely to arise from electrostatic stiffening, as
evidenced by the ionic-strength dependency of titin-based myofibril stiffness; at
high stretch, hydrophobic effects also might become relevant. Thus, at
physiological muscle lengths, the PEVK region does not function as a pure
entropic spring. Rather, PEVK elasticity may have both entropic and enthalpic
origins characterizable by a polymer persistence length and a stretch modulus.
PMID- 9653139
TI - Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins
by the ubiquitin pathway.
AB - We have previously shown that the degradation of c-myc and N-myc in vitro is
mediated by the ubiquitin system. However, the role of the system in targeting
the myc proteins in vivo and the identity of the conjugating enzymes and possible
ancillary proteins involved has remained obscure. Here we report that the
degradation of the myc proteins in cells is inhibited by lactacystin and MG132,
two inhibitors of the 20S proteasome. Inhibition is accompanied by accumulation
of myc-ubiquitin conjugates. Dissection of the ancillary proteins involved
revealed that the high-risk human papillomavirus oncoprotein E6-16 stimulates
conjugation and subsequent degradation of the myc proteins in vitro. Expression
of E6-16 in cells results in significant shortening of the t1/2 of the myc
proteins with subsequent decrease in their cellular level. Analysis of the
conjugating enzymes revealed that under basal conditions the proteins can be
conjugated by two pairs of E2s and E3s-E2-14 kDa and E3alpha involved in the "N
end rule" pathway, and E2-F1 (UbcH7) and E3-Fos involved also in conjugation of c
Fos. In the presence of E6-16, a third pair, E2-F1 and E6-AP mediate conjugation
of myc by means of a mechanism that appears to be similar to that involved in the
targeting of p53, formation of a myc. E6.E6-AP targeting complex. It is possible
that in certain cells E6-mediated targeting of myc prevents myc-induced apoptosis
and thus ensures maintenance of viral infection.
PMID- 9653140
TI - Desmosomal adhesion inhibits invasive behavior.
AB - Recent studies of human disease and transgenic animal experiments have clearly
demonstrated the importance of desmosomes in normal tissue architecture.
Furthermore, desmosomal components are down-regulated in certain types of
carcinomas, suggesting a possible role for desmosomes in suppression of invasion
and metastasis. However, there is no functional evidence to support such a
hypothesis. To obtain such evidence, we needed to generate desmosomal adhesion in
an invasive cell line. We show that expression of multiple desmosomal components
(the desmosomal cadherins, desmocollin and desmoglein, and the armadillo protein,
plakoglobin) in nonadhesive L929 fibroblasts generates adhesion in aggregation
assays. This adhesion is specifically blocked by short peptides corresponding to
the putative cell adhesion recognition sites of desmocollin and desmoglein. This
result provides an experimental demonstration of the functional importance of the
cell adhesion recognition sites of desmocollin and desmoglein and indicates that
both desmosomal cadherins are specifically involved in this adhesion. Moreover,
whereas parental L929 cells are strongly invasive into collagen gels, we show
that invasion is substantially inhibited in cells transfected with desmosomal
components. Invasion is restored by treating the transfected cells with anti
adhesion peptides, indicating that desmosomal adhesion specifically blocks
invasion in culture. Our results support the suggestion that desmosomes have a
role in suppression of tumor spreading.
PMID- 9653141
TI - Coactivation of two different G protein-coupled receptors is essential for ADP
induced platelet aggregation.
AB - ADP is an important platelet agonist causing shape change and aggregation
required for physiological hemostasis. We recently demonstrated the existence of
two distinct G protein-coupled ADP receptors on platelets, one coupled to
phospholipase C, P2Y1, and the other to inhibition of adenylyl cyclase, P2TAC. In
this study, using specific antagonists for these two receptors, we demonstrated
that concomitant intracellular signaling from both the P2TAC and P2Y1 receptors
is essential for ADP-induced platelet aggregation. Inhibition of signaling
through either receptor, by specific antagonists, is sufficient to block ADP
induced platelet aggregation. Furthermore, signaling through the P2TAC receptor
could be replaced by activation of alpha2A-adrenergic receptors. On the other
hand, activation of serotonin receptors supplements signaling through the P2Y1
receptor. Moreover, this mechanism of ADP-induced platelet aggregation could be
mimicked by coactivation of two non-ADP receptors coupled to Gi and Gq, neither
of which can cause platelet aggregation by itself. We propose that platelet
aggregation results from concomitant signaling from both the Gi and Gq, a
mechanism by which G protein-coupled receptors elicit a physiological response.
PMID- 9653142
TI - ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the
proton pump in endocytotically active kidney cells.
AB - Loss-of-function mutations of the ClC-5 chloride channel lead to Dent's disease,
a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and
kidney stones. We show that ClC-5 is expressed in renal proximal tubule cells,
which normally endocytose proteins passing the glomerular filter. Expression is
highest below the brush border in a region densely packed with endocytotic
vesicles, where ClC-5 colocalizes with the H+-ATPase and with internalized
proteins early after uptake. In intercalated cells of the collecting duct it
again localizes to apical intracellular vesicles and colocalizes with the proton
pump in alpha-intercalated cells. In transfected cells, ClC-5 colocalizes with
endocytosed alpha2-macroglobulin. Cotransfection with a GTPase-deficient rab5
mutant leads to enlarged early endosomes that stain for ClC-5. We suggest that
ClC-5 may be essential for proximal tubular endocytosis by providing an
electrical shunt necessary for the efficient acidification of vesicles in the
endocytotic pathway, explaining the proteinuria observed in Dent's disease.
PMID- 9653143
TI - Evidence for a role of NF-kappaB in the survival of hematopoietic cells mediated
by interleukin 3 and the oncogenic TEL/platelet-derived growth factor receptor
beta fusion protein.
AB - Interleukin 3 (IL-3) and other hematopoietic cytokines transduce signals that
stimulate DNA synthesis and cell survival. In certain chronic myelomonocytic
leukemias, a TEL/platelet-derived growth factor receptor beta (PDGFRbeta) fusion
protein is produced as a consequence of the t(5;12) translocation. It contains
the amino terminus of the transcription factor TEL fused to the transmembranous
and cytoplasmic domains of the PDGFRbeta. It is oncogenic as it substitutes for
IL-3, thus promoting cell growth and preventing apoptotic cell death. The
mechanism by which TEL/PDGFRbeta generates survival signals remains undefined.
Here, we report that both IL-3 and TEL/PDGFRbeta initiate a signaling cascade
that leads to the activation of the transcriptional factor NF-kappaB. In fact,
either cytokine deprivation of IL-3-dependent Ba/F3 cells or exposure of
TEL/PDGFRbeta-expressing cells to the specific inhibitor of the PDGFR tyrosine
kinase, CGP53716, caused a strong decrease in NF-kappaB activity followed by
extensive cell death. Further, treatment with the proteasome inhibitor Z-IE(O-t
Bu)A-leucinal suppressed IL-3 and TEL/PDGFRbeta-dependent survival. The same
result was seen upon overexpression of an unphosphorylable form of IkappaBalpha.
Because both conditions inactivate NF-kappaB by preventing its translocation into
the nucleus, that process seems to be essential for cell survival in response to
IL-3 and TEL/PDGFRbeta. Moreover, overexpression of a dominant-negative mutant of
the protooncogene c-Myc, a downstream target of NF-kappaB, had a similar effect.
We conclude that NF-kappaB plays an important role in maintaining cell survival
in response to IL-3 and TEL/PDGFRbeta and that c-Myc may be a downstream effector
mediating this effect.
PMID- 9653144
TI - Identification of a human PTS1 receptor docking protein directly required for
peroxisomal protein import.
AB - The discovery of many fatal human disorders resulting from impaired peroxisomal
protein import makes the functional characterization of human peroxins critical.
As part of our attempt to identify novel human genes and gene products involved
in the import of peroxisomal proteins, we raised antisera against peroxisomal
membrane proteins. One such antiserum inhibited peroxisomal protein import in
semipermeabilized mammalian cells. This "import inhibiting" antiserum, ab-MF3,
specifically recognized a 57-kDa protein. Immunoblot analysis of rat liver
subcellular fractions demonstrated that this protein was present exclusively in
peroxisomal membranes. Functional analysis revealed that this 57-kDa molecule
bound the PTS1 receptor, Pex5p, in ligand blots, suggesting it is a docking site
on the peroxisomal membrane. Previous studies have identified two yeast proteins,
Pex14p and Pex13p, as Pex5p-binding proteins. To facilitate the biochemical
analysis of peroxisomal membrane docking proteins, we cloned and expressed the
previously unidentified human Pex14p, as well as a human Pex13p that is 39 aa
longer than previously reported. Recombinant Pex14p was specifically recognized
by the "import inhibiting" ab-MF3 and bound Pex5p and the Src homology 3 (SH3)
domain of Pex13p in ligand blots. These studies demonstrate that the ab-MF3
immunoreactive, 57-kDa peroxisomal membrane protein is Pex14p. Furthermore, this
peroxin interacts with Pex5p and Pex13p(SH3) and is directly required for
peroxisomal protein import.
PMID- 9653145
TI - Targeted expansion of genetically modified bone marrow cells.
AB - The ability to specifically target a mitogenic signal to a population of
genetically modified primary cells would have potential applications both for
gene and cell therapy. Toward this end, a gene encoding a fusion protein
containing the FK506-binding protein FKBP12, fused to the intracellular portion
of the receptor for thrombopoietin (mpl), was introduced into primary murine bone
marrow cells. Dimerization of this fusion protein through the addition of a
dimeric form of the drug FK506, called FK1012, resulted in a marked proliferative
expansion of marrow cells that was restricted to the genetically modified
population. FK1012's proliferative effect was sustained and reversible. An
apparent preference for differentiation along the megakaryocytic lineage was
observed. This approach allows for the specific delivery of a mitogenic signal to
a population of genetically modified primary cells and may have applications for
studies in hematopoiesis and receptor biology, and for gene and cell therapy.
PMID- 9653146
TI - Phospholipase A2-mediated activation of mitogen-activated protein kinase by
angiotensin II.
AB - In renal proximal tubule epithelial cells, a membrane-associated phospholipase A2
(PLA2) is a major signaling pathway linked to angiotensin II (Ang II) type 2
receptor (AT2). The current studies were designed to test the hypothesis that
membrane-associated PLA2-induced release of arachidonic acid (AA) and/or its
metabolites may serve as an upstream mediator of Ang II-induced mitogen-activated
protein kinase (MAPK) activation. Ang II stimulated transient dose-dependent
phosphorylation of MAPK with a maximum at 1 microM (10 min). Inhibition of PLA2
by mepacrine diminished both AA release and MAPK phosphorylation, induced by Ang
II. Furthermore, AA itself induced time- and dose-dependent phosphorylation of
MAPK, supporting the importance of PLA2 as a mediator of Ang II signaling. The
effects of both Ang II and AA on MAPK phosphorylation were protein kinase C
independent and abolished by the inhibitor of cytochrome P450 isoenzyme,
ketoconazole. Moreover, 5,6-epoxyeicosatrienoic acid and 14,15
epoxyeicosatrienoic acid, the cytochrome P450-dependent metabolites of AA,
significantly stimulated MAPK activity in renal proximal tubule epithelial cells.
These observations document a mechanism of Ang II-induced MAPK phosphorylation,
mediated by PLA2-dependent release of AA and cytochrome P450-dependent production
of epoxy derivatives of AA.
PMID- 9653147
TI - Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species.
AB - Arsenite, the trivalent form of arsenic present in the environment, is a known
human carcinogen that lacked mutagenic activity in bacterial and standard
mammalian cell mutation assays. We show herein that when evaluated in an assay
(AL cell assay), in which both intragenic and multilocus mutations are
detectable, that arsenite is in fact a strong dose-dependent mutagen and that it
induces mostly large deletion mutations. Cotreatment of cells with the oxygen
radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of
arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part
by it being a mutagen that depends on reactive oxygen species for its activity.
PMID- 9653148
TI - The Notch1 receptor is cleaved constitutively by a furin-like convertase.
AB - The Notch receptor, which is involved in numerous cell fate decisions in
invertebrates and vertebrates, is synthesized as a 300-kDa precursor molecule
(p300). We show here that proteolytic processing of p300 is an essential step in
the formation of the biologically active receptor because only the cleaved
fragments are present at the cell surface. Our results confirm and extend recent
reports indicating that the Notch receptor exists at the plasma membrane as a
heterodimeric molecule, but disagree as to the nature of the protease that is
responsible for the cleavage that takes place in the extracellular region. We
report here that constitutive processing of murine Notch1 involves a furin-like
convertase. We show that the calcium ionophore A23187 and the alpha1-antitrypsin
variant, alpha 1-PDX, a known inhibitor of furin-like convertases, inhibit p300
processing. When expressed in the furin-deficient Lovo cell line, p300 is not
processed. In vitro digestion of a recombinant Notch-derived substrate with
purified furin allowed mapping of the processing site to the carboxyl side of the
sequence RQRR (amino acids 1651-1654). Mutation of these four amino acids (and of
two secondary dibasic furin sites located nearby) completely abolished processing
of the Notch1 receptor.
PMID- 9653149
TI - Jasmonate-induced responses are costly but benefit plants under attack in native
populations.
AB - Herbivore attack is widely known to reduce food quality and to increase chemical
defenses and other traits responsible for herbivore resistance. Inducible
defenses are commonly thought to allow plants to forgo the costs of defense when
not needed; however, neither their defensive function (increasing a plant's
fitness) nor their cost-savings function have been demonstrated in nature. The
root-produced toxin nicotine increases after herbivore attack in the native,
postfire annual Nicotiana attenuata and is internally activated by the wound
hormone, jasmonic acid. I treated the roots of plants with the methyl ester of
this hormone (MeJA) to elicit a response in one member of each of 745 matched
pairs of plants growing in native populations with different probabilities of
attack from herbivores, and measured the lifetime production of viable seed. In
populations with intermediate rates of attack, induced plants were attacked less
often by herbivores and survived to produce more seed than did their uninduced
counterparts. Previous induction did not significantly increase the fitness of
plants suffering high rates of attack. However, if plants had not been attacked,
induced plants produced less seed than did their uninduced counterparts.
Jasmonate-induced responses function as defenses but are costly, and inducibility
allows this species to forgo these costs when the defenses are unnecessary.
PMID- 9653150
TI - Genetic evidence for a Paleolithic human population expansion in Africa.
AB - Human populations have undergone dramatic expansions in size, but other than the
growth associated with agriculture, the dates and magnitudes of those expansions
have never been resolved. Here, we introduce two new statistical tests for
population expansion, which use variation at a number of unlinked genetic markers
to study the demographic histories of natural populations. By analyzing genetic
variation in various aboriginal populations from throughout the world, we show
highly significant evidence for a major human population expansion in Africa, but
no evidence of expansion outside of Africa. The inferred African expansion is
estimated to have occurred between 49,000 and 640,000 years ago, certainly before
the Neolithic expansions, and probably before the splitting of African and non
African populations. In showing a significant difference between African and non
African populations, our analysis supports the unique role of Africa in human
evolutionary history, as has been suggested by most other genetic work. In
addition, the missing signal in non-African populations may be the result of a
population bottleneck associated with the emergence of these populations from
Africa, as postulated in the "Out of Africa" model of modern human origins.
PMID- 9653151
TI - The evolution of primate malaria parasites based on the gene encoding cytochrome
b from the linear mitochondrial genome.
AB - We report a phylogenetic analysis of primate malaria parasites based on the gene
encoding the cytochrome b protein from the mitochondrial genome. We have studied
17 species of Plasmodium, including 14 parasitic in primates. In our analysis,
four species were used for rooting the Plasmodium phylogenetic tree: two from
closely related genera (Hepatocystis sp. and Haemoproteus columbae) and two other
Apicomplexa (Toxoplasma gondii and Theileria parva). We found that primate
malaria parasites form a monophyletic group, with the only exception being the
Plasmodium falciparum-Plasmodium reichenowi lineage. Phylogenetic analyses that
include two species of non-Plasmodium Haemosporina suggest that the genus
Plasmodium is polyphyletic. We conclude that the biologic traits, such as
periodicity and the capacity to relapse, have limited value for assessing the
phylogenetic relationships among Plasmodium species. For instance, we found no
evidence that would link virulence with the age of the host-parasite association.
Our studies also reveal that the primate malaria parasites originated in Africa,
which contradicts the presently held opinion of Southeast Asia as their center of
origin. We propose that the radiation of Asian monkey parasites is a recent event
where several life history traits, like differences in periodicity, appeared de
novo.
PMID- 9653152
TI - Molecular population genetics of the Arabidopsis CAULIFLOWER regulatory gene:
nonneutral evolution and naturally occurring variation in floral homeotic
function.
AB - The evolution of interspecies differences in morphology requires sufficient
within-species variation in developmental regulatory systems on which
evolutionary forces can act. Molecular analyses of naturally occurring alleles of
the Arabidopsis thaliana CAULIFLOWER locus reveal considerable intraspecific
diversity at this floral homeotic gene, and the McDonald-Kreitman test suggests
that this gene is evolving in a nonneutral fashion, with an excess of
intraspecific replacement polymorphisms. The naturally occurring molecular
variation within this floral regulatory gene is associated with functionally
different alleles, which can be distinguished phenotypically by their
differential ability to direct floral meristem development.
PMID- 9653153
TI - Rice (Oryza sativa) centromeric regions consist of complex DNA.
AB - Rice bacterial artificial chromosome clones containing centromeric DNA were
isolated by using a DNA sequence (pSau3A9) that is present in the centromeres of
Gramineae species. Seven distinct repetitive DNA elements were isolated from a 75
kilobase rice bacterial artificial chromosome clone. All seven DNA elements are
present in every rice centromere as demonstrated by fluorescence in situ
hybridization. Six of the elements are middle repetitive, and their copy numbers
range from approximately 50 to approximately 300 in the rice genome. Five of
these six middle repetitive DNA elements are present in all of the Gramineae
species, and the other element is detected only in species within the
Bambusoideae subfamily of Gramineae. All six middle repetitive DNA elements are
dispersed in the centromeric regions. The seventh element, the RCS2 family, is a
tandem repeat of a 168-bp sequence that is represented approximately 6,000 times
in the rice genome and is detected only in Oryza species. Fiber-fluorescence in
situ hybridization analysis revealed that the RCS2 family is organized into long
uninterrupted arrays and resembles previously reported tandem repeats located in
the centromeres of human and Arabidopsis thaliana chromosomes. We characterized a
large DNA fragment derived from a plant centromere and demonstrated that rice
centromeres consist of complex DNA, including both highly and middle repetitive
DNA sequences.
PMID- 9653154
TI - Molecular characterization of a common fragile site (FRA7H) on human chromosome 7
by the cloning of a simian virus 40 integration site.
AB - Common fragile sites are chromosomal loci prone to breakage and rearrangement,
hypothesized to provide targets for foreign DNA integration. We cloned a simian
virus 40 integration site and showed by fluorescent in situ hybridization
analysis that the integration event had occurred within a common aphidicolin
induced fragile site on human chromosome 7, FRA7H. A region of 161 kb spanning
FRA7H was defined and sequenced. Several regions with a potential unusual DNA
structure, including high-flexibility, low-stability, and non-B-DNA-forming
sequences were identified in this region. We performed a similar analysis on the
published FRA3B sequence and the putative partial FRA7G, which also revealed an
impressive cluster of regions with high flexibility and low stability. Thus,
these unusual DNA characteristics are possibly intrinsic properties of common
fragile sites that may affect their replication and condensation as well as
organization, and may lead to fragility.
PMID- 9653155
TI - Evolution of the avian sex chromosomes from an ancestral pair of autosomes.
AB - Among the mechanisms whereby sex is determined in animals, chromosomal sex
determination is found in a wide variety of distant taxa. The widespread but not
ubiquitous occurrence, not even within lineages, of chromosomal sex determination
suggests that sex chromosomes have evolved independently several times during
animal radiation, but firm evidence for this is lacking. The most favored model
for this process is gradual differentiation of ancestral pairs of autosomes. As
known for mammals, sex chromosomes may have a very ancient origin, and it has
even been speculated that the sex chromosomes of mammals and birds would share a
common chromosomal ancestry. In this study we showed that the two genes, ATP5A1
and CHD1, so far assigned to the female-specific W chromosome of birds both exist
in a very closely related copy on the Z chromosome but are not pseudoautosomal.
This indicates a common ancestry of the two sex chromosomes, consistent with the
evolution from a pair of autosomes. Comparative mapping demonstrates, however,
that ATP5A1 and CHD1 are not sex-linked among eutherian mammals; this is also not
the case for the majority of other genes so far assigned to the avian Z
chromosome. Our results suggest that the evolution of sex chromosomes has
occurred independently in mammals and birds.
PMID- 9653156
TI - Localization of tumor suppressor activity important in nonsmall cell lung
carcinoma on chromosome 11q.
AB - Loss of heterozygosity on chromosome 11q23 is observed at high frequency in human
nonsmall cell lung carcinomas (NSCLCs), suggesting the presence of a tumor
suppressor gene. Previous analysis of DNA from 79 patients identified a commonly
deleted segment of 5 centimorgans. Complementation analysis was used to further
localize a putative tumor suppressor gene. Three yeast artificial chromosome
(YAC) clones spanning the minimal loss of heterozygosity region were modified,
and spheroplast fusion was used to transfer them into human A549 NSCLC or murine
Lewis lung carcinoma (LLC) cell lines. The resulting yeast x human hybrid cell
lines containing an intact copy of a 1.6-Mb YAC, 939b12, showed reduced growth in
vitro. Injection of parental A549 cells into athymic (nu/nu) mice resulted in
tumor formation at 27 of 28 injection sites. In contrast, two independent 939b12
containing cell lines formed tumors at only 3 of 20 injection sites. 939b12 also
suppressed tumor formation by LLC NSCLC cells in nude mice, but YACs 785e12 and
911f2, which flank 939b12, had no suppressor activity. Further localization of
tumor suppression activity on 939b12 was accomplished by introduction of defined
fragmentation derivatives into A549 cells and by analysis of YACs that were
broken on transfer into LLC cells. This complementation approach localized tumor
suppression activity to the central 700 kb of 939b12 and provides a functional
assay for positional cloning of this tumor suppressor gene.
PMID- 9653157
TI - sud1(+) targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins
for degradation and stops unwanted diploidization in fission yeast.
AB - In the fission yeast Schizosaccharomyces pombe, S phase is limited to a single
round per cell cycle through cyclin-dependent kinase phosphorylation of critical
replication factors, including the Cdc18 replication initiator protein. Because
defects in Cdc18 phosphorylation lead to a hyperstable and hyperactive form of
Cdc18 that promotes high levels of overreplication in vivo, we wished to identify
the components of the Cdc18 proteolysis pathway in fission yeast. In this paper
we describe one such component, encoded by the sud1(+) gene. sud1(+) shares
homology with the budding yeast CDC4 gene and is required to prevent spontaneous
re-replication in fission yeast. Cells lacking sud1(+) accumulate high levels of
Cdc18 and the CDK inhibitor Rum1, because they cannot degrade these two key cell
cycle regulators. Through genetic analysis we show that hyperaccumulation of Rum1
contributes to re-replication in Deltasud1 cells, but is not the cause of the
defect in Cdc18 proteolysis. Rather, Sud1 itself is associated with the ubiquitin
pathway in fission yeast and binds to Cdc18 in vivo. Most importantly, Sud1-Cdc18
binding requires prior phosphorylation of the Cdc18 polypeptide at CDK consensus
sites. These results provide a biochemical mechanism for the phosphorylation
dependent degradation of Cdc18 and other cell cycle regulators, including Rum1.
Evolutionary conservation of the Sud1/CDC4 pathway suggests that phosphorylation
coupled proteolysis may be a general feature of nearly all eukaryotic cell
cycles.
PMID- 9653158
TI - Single amino acid substitution in prokaryote polypeptide release factor 2 permits
it to terminate translation at all three stop codons.
AB - Prokaryotic translational release factors, RF1 and RF2, catalyze polypeptide
release at UAG/UAA and UGA/UAA stop codons, respectively. In this study, we
isolated a bacterial RF2 mutant (RF2*) containing an E167K substitution that
restored the growth of a temperature-sensitive RF1 strain of Escherichia coli and
the viability of a chromosomal RF1/RF2 double knockout. In both in vivo and in
vitro polypeptide termination assays, RF2* catalyzed UAG/UAA termination, as does
RF1, as well as UGA termination, showing that RF2* acquired omnipotent release
activity. This result suggests that the E167K mutation abolished the putative
third-base discriminator function of RF2. These findings are interpreted as
indicating that prokaryotic and eukaryotic release factors share the same
anticodon moiety and that only one omnipotent release factor is sufficient for
bacterial growth, similar to the eukaryotic single omnipotent factor.
PMID- 9653159
TI - Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a
balanced polymorphism for regulation of bilirubin metabolism?
AB - A polymorphism in the promoter of the UDP-glucuronosyltransferase 1 (UGT1A1) gene
has been shown to cause Gilbert syndrome, a benign form of unconjugated
bilirubinemia. Promoters containing seven thymine adenine (ta) repeats have been
found to be less active than the wild-type six repeats, and the serum bilirubin
levels of persons homozygous or even heterozygous for seven repeats have been
found to be higher than those with the wild-type six repeats. We have now
examined the genotypes in persons of Asian, African, and Caucasian ancestry.
Although within the Caucasian ethnic group there is a strong correlation between
promoter repeat number and bilirubin level, between ethnic groups we found that
this relationship to be inverse. Among people of African ancestry there are, in
addition to those with six and seven repeats, also persons who have five or eight
repeats. Using a reporter gene we show that there is an inverse relationship
between the number of ta repeats and the activity of the promoter through the
range of 5-8 ta repeats. An incidental finding was a polymorphism at nucleotide
106, tightly linked to the (ta)5 haplotype. Serum bilirubin levels are influenced
by many factors, both genetic and environmental. We suggest that the unstable
UGT1A1 polymorphism may serve to "fine-tune" the plasma bilirubin level within
population groups, maintaining it at a high enough level to provide protection
against oxidative damage, but at a level that is sufficiently low to prevent
kernicterus in infants.
PMID- 9653160
TI - Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor
cells by expressed sequence tags and efficient full-length cDNA cloning.
AB - Hematopoietic stem/progenitor cells (HSPCs) possess the potentials of self
renewal, proliferation, and differentiation toward different lineages of blood
cells. These cells not only play a primordial role in hematopoietic development
but also have important clinical application. Characterization of the gene
expression profile in CD34(+) HSPCs may lead to a better understanding of the
regulation of normal and pathological hematopoiesis. In the present work, genes
expressed in human umbilical cord blood CD34(+) cells were catalogued by
partially sequencing a large amount of cDNA clones [or expressed sequence tags
(ESTs)] and analyzing these sequences with the tools of bioinformatics. Among
9,866 ESTs thus obtained, 4,697 (47.6%) showed identity to known genes in the
GenBank database, 2, 603 (26.4%) matched to the ESTs previously deposited in a
public domain database, 1,415 (14.3%) were previously undescribed ESTs, and the
remaining 1,151 (11.7%) were mitochondrial DNA, ribosomal RNA, or repetitive (Alu
or L1) sequences. Integration of ESTs of known genes generated a profile
including 855 genes that could be divided into different categories according to
their functions. Some (8.2%) of the genes in this profile were considered related
to early hematopoiesis. The possible function of ESTs corresponding to so far
unknown genes were approached by means of homology and functional motif searches.
Moreover, attempts were made to generate libraries enriched for full-length
cDNAs, to better explore the genes in HSPCs. Nearly 60% of the cDNA clones of
mRNA under 2 kb in our libraries had 5' ends upstream of the first ATG codon of
the ORF. With this satisfactory result, we have developed an efficient working
system that allowed fast sequencing of 32 full-length cDNAs, 16 of them being
mapped to the chromosomes with radiation hybrid panels. This work may lay a basis
for the further research on the molecular network of hematopoietic regulation.
PMID- 9653161
TI - Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli
Opitz syndrome.
AB - The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism
with characteristic congenital malformations and dysmorphias. All patients suffer
from mental retardation. Here we identify the SLOS gene as a Delta7-sterol
reductase (DHCR7, EC 1.3.1. 21) required for the de novo biosynthesis of
cholesterol. The human and murine genes were characterized and assigned to
syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ
hybridization. Among the mutations found in patients with the SLOS, are missense
(P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense
(W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame
deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and
G410S reduced heterologous protein expression by >90%. Our results strongly
suggest that defects in the DHCR7 gene cause the SLOS.
PMID- 9653162
TI - HD mice: a novel mouse mutant with a specific defect in the generation of CD4(+)
T cells.
AB - We have identified a spontaneous mutation in mice, which we term HD for "helper T
cell deficient." This mouse is distinguished by the virtual absence of peripheral
T cells of the CD4(+)8(-) major histocompatibility complex (MHC) class II
restricted T helper subset due to a specific block in thymic development. The
developmental defect is selective for CD4(+)8(-) cells; the maturation of CD4(
)8(+) and gamma delta T cells is normal. The autosomal recessive mutation
underlying the HD phenotype is unrelated to MHC class II, since it segregates
independently of the MHC class II locus. Moreover, the HD phenotype is not caused
by a defect of the CD4 gene. Bone marrow transfer experiments demonstrate that
the defect is intrinsic to cells of the hematopoietic lineage, i.e., most likely
to developing thymocytes themselves. The frequency of CD4(+)8(low) intermediate
cells is markedly increased in HD mice, suggesting that class II-restricted
thymocytes are arrested at this stage. This is the first genetic defect of its
kind to be described in the mouse and may prove highly informative in
understanding the molecular pathways underlying lineage commitment.
PMID- 9653163
TI - Altered peptide ligands induce quantitatively but not qualitatively different
intracellular signals in primary thymocytes.
AB - Interaction of the T cell receptor (TCR) with peptide/major histocompatibility
complexes (MHC) in the thymus is of critical importance for developing
thymocytes. In a previous study, we described an antagonist peptide that
inhibited negative selection of transgenic thymocytes induced by an agonist
peptide. In this study we show that this antagonist peptide can induce positive
selection of CD8(+) thymocytes more efficiently than the agonist or the weak
agonist peptides, whereas the opposite is true for their ability to cause
negative selection. The intracellular signals induced in thymocytes by such
peptides after TCR ligation was examined in CD4(+)8(+) double-positive thymocytes
from F5/beta2mo/Rag-1(o) transgenic mice. TCR ligation with either the agonist,
weak agonist, or antagonist peptide variants resulted in hyperphosphorylation of
CD3zeta, CD3epsilon, ZAP-70, Syk, Vav, SLP-76, and pp36-38. The extent of
phosphorylation of these intracellular proteins correlated with the efficiency
with which the peptide analogs induced apoptosis of immature thymocytes.
Unexpectedly, there was no correlation between the upstream TCR signaling
pathways analyzed and the capacity of the different peptides to induce positive
selection.
PMID- 9653164
TI - Intrathymic selection of NK1.1(+)alpha/beta T cell antigen receptor (TCR)+ cells
in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I
Ad.
AB - Generation and negative selection of NK1.1(+)alpha/beta T cell receptor (TCR)+
thymocytes were analyzed using TCR-transgenic (B10. D2 x DO10)F1 and (C57BL/6 x
DO10)F1 mice and Rag-1(-/-)/DO10 mice, which had been established by breeding and
backcrossing between Rag-1(-/-) and DO10 mice. Almost all T cells from these mice
were shown to bear Valpha13/Vbeta8.2 that is specific for chicken ovalbumin
(cOVA) and restricted to I-Ad. A normal proportion of the NK1.1(+)
Valpha13/Vbeta8.2(+) thymocytes was generated in these mice. However, the actual
cell number of both NK1.1(+) and NK1.1(-) thymocytes in I-Ad/d mice (positive
selecting background) was larger than that in I-Ab/d mice (negative selecting
background). Markedly low but significant proportions of NK1.1(+)
Valpha13/Vbeta8.2(+) cells were detected in the spleens from I-Ad/d and I-Ab/d
mice. It was shown that the splenic NK1.1(+) T cells of the I-Ab/d mice were
anergized against stimulation through TCR. When (B10.D2 x DO10)F1 and (C57BL/6 x
DO10)F1 mice were given cOVA, extensive or intermediate elimination of
NK1.1(+)alpha/betaTCR+ thymocytes was induced in I-Ad/d or I-Ab/d mice,
respectively. However, the clonal elimination was not as complete as that seen in
the major NK1.1(-) thymocyte population. The present findings indicate that
normal generation of NK1.1(+)alpha/betaTCR+ thymocytes occurs in the absence of
Valpha14-Jalpha281 and that substantial negative selection operates on the
NK1.1(+)alpha/betaTCR+ cells.
PMID- 9653165
TI - The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3.
AB - We cloned the mouse homologue of the chemokine receptor CXCR3, which is located
in mouse chromosome X. We screened a large panel of chemokines for their ability
to induce a calcium flux in mouse CXCR3-transfected cells and identified a new
ligand for this receptor, the recently reported CC chemokine 6Ckine. This
represents an example of a CC chemokine, which binds to a CXC chemokine receptor.
Like other ligands of this receptor, 6Ckine has angiostatic properties. 6Ckine is
known to chemoattract T cells. In line with this, CXCR3 is expressed
preferentially in Th1 cells and in lymphoid organs of the IL-10(-/-) mouse that
develops chronic colitis. Its ability to attract T cells as well as its
angiostatic properties suggest that 6Ckine may be an effective anti-tumor agent.
PMID- 9653166
TI - Efficient adenoviral infection with IkappaB alpha reveals that macrophage tumor
necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent.
AB - Tumor necrosis factor (TNF) alpha has been shown to be a major therapeutic target
in rheumatoid arthritis with the success of anti-TNFalpha antibody clinical
trials. Although signaling pathways leading to TNFalpha expression have been
studied in some detail, there is evidence for considerable differences between
individual cell types. This prompted us to investigate the intracellular
signaling pathways that result in increased TNFalpha synthesis from macrophages
in the diseased synovial joint tissue. Using an adenoviral system in vitro we
report the successful delivery of genes to more than 95% of normal human
macrophages. This permitted us to show, by using adenoviral transfer of IkappaB
alpha, the natural inhibitor of NF-kappaB, that induction of TNFalpha in normal
human macrophages by lipopolysaccharide, but not by some other stimuli, was
inhibited by 80%. Furthermore the spontaneous production of TNFalpha from human
rheumatoid joint cell cultures was inhibited by 75%, indicating that the NF
kappaB pathway is an essential step for TNFalpha synthesis in synovial
macrophages and demonstrating that NF-kappaB should be an effective therapeutic
target in this disease.
PMID- 9653167
TI - Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect
mice against lethal challenge with malignant melanoma cells expressing a model
antigen.
AB - Recombinant polioviruses expressing foreign antigens may provide a convenient
vaccine vector system to induce protective immunity against diverse pathogens.
Replication-competent chimeric viruses can be constructed by inserting foreign
antigenic sequences within the poliovirus polyprotein. When inserted sequences
are flanked by poliovirus protease recognition sites the recombinant polyprotein
is processed to mature and functional viral proteins plus the exogenous antigen.
It previously has been shown that poliovirus recombinants can induce antibody
responses against the inserted sequences but it is not known whether poliovirus
or vaccine vectors derived from it can elicit effective cytotoxic T lymphocyte
(CTL) responses. To examine the ability of the recombinant poliovirus to induce
CTL responses, a segment of the chicken ovalbumin gene, which includes the H2-Kb
restricted CTL epitope SIINFEKL, was cloned at the junction of the P1 and P2
regions. This recombinant virus replicated with near wild-type efficiency in
culture and stably expressed high levels of the ovalbumin antigen. Murine and
primate cells infected with the recombinant virus appropriately processed the
SIINFEKL epitope and presented it within major histocompatibility complex class I
molecules. Inoculation of mice with recombinant poliovirus that expresses
ovalbumin elicits an effective specific CTL response. Furthermore, vaccination
with these recombinant poliovirus induced protective immunity against challenge
with lethal doses of a malignant melanoma cell line expressing ovalbumin.
PMID- 9653168
TI - Interleukin 6 plays a key role in the development of antigen-induced arthritis.
AB - To investigate the direct role of interleukin (IL) 6 in the development of
rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight
generations into C57BL/6 mice, a strain of mice with a genetic background of
susceptibility for antigen-induced arthritis (AIA). Both histological and
immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and
wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6
+/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/-
mice. Safranin O staining demonstrated that articular cartilage was well
preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice.
In addition, comparable mRNA expression for both IL-1beta and tumor necrosis
factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/-
mice, suggesting that IL-6 may play a more crucial role in cartilage destruction
than either IL-1beta or tumor necrosis factor alpha. In immunological
comparisons, both antigen-specific in vitro proliferative response in lymph node
cells and in vivo antibody production were elicited in IL-6 -/- mice, but they
were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells
of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with
either antigen-specific or nonspecific stimulation in in vitro culture. Taken
together, these results indicate that IL-6 may play a key role in the development
of AIA at the inductive as well as the effector phase, and the blockade of IL-6
is possibly beneficial in the treatment of rheumatoid arthritis.
PMID- 9653169
TI - Human parvovirus B19 as a causative agent for rheumatoid arthritis.
AB - Human parvovirus B19 (B19) DNA was detected in the synovial tissues in 30 of 39
patients with rheumatoid arthritis (RA), and infrequently in those with
osteoarthritis and traumatic joints. On the other hand, the expression of the B19
antigen VP-1 was specific (27/27) in RA synovium with active synovial lesions,
but not in osteoarthritis and controls. The target cells of B19 were macrophages,
follicular dendritic cells, T cells, and B cells, but not synovial lining cells
in the synovium. B19-negative bone marrow cells, tonsil cells, and macrophage
cell line U-937 cells became positive for the expression of VP-1, and more
productive for interleukin 6 and tumor necrosis factor alpha when cocultured with
RA synovial cells. The expression of VP-1 and the production of interleukin 6 and
tumor necrosis factor alpha was significantly inhibited by the addition of
neutralizing antibody for B19, suggesting that B19 detected in RA synovial cells
is infective. B19 is involved in the initiation and perpetuation of RA synovitis,
leading to joint lesions.
PMID- 9653170
TI - Targeted disruption of the interferon-gamma receptor 2 gene results in severe
immune defects in mice.
AB - To study the role of the interferon- (IFN) gammaR2 chain in IFN-gamma signaling
and immune function, IFN-gammaR2-deficient mice have been generated and
characterized. Cells derived from IFN-gammaR2 -/- mice are unable to activate
either JAK/STAT signaling proteins or gene transcription in response to IFN
gamma. The lack of IFN-gamma responsiveness alters IFN-gamma-induced Ig class
switching by B cells from these mice. In vitro cultures of T cells demonstrate
that the T cells from the IFN-gammaR2 -/- mice have a defect in Th1 cell
differentiation. The IFN-gammaR2 (-/-) mice also produce lower amounts of IFN
gamma in response to antigenic challenge. In addition, IFN-gammaR2 -/- mice are
defective in contact hypersensitivity and are highly susceptible to infection by
Listeria monocytogenes. These results demonstrate that the IFN-gammaR2 is
essential for IFN-gamma-mediated immune responses in vivo.
PMID- 9653171
TI - Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal
human hematopoietic cells.
AB - Many chimeric oncogenes have been identified by virtue of the association between
chromosomal translocation and specific human leukemias. However, the biological
mechanism by which these oncogenes disrupt the developmental program of normal
human hematopoietic cells during the initiation of the leukemogenic process is
poorly understood due to the absence of an appropriate experimental system to
study their function. Here, we report that retroviral transduction of TLS-ERG, a
myeloid leukemia-associated fusion gene, to human cord blood cells results in
altered myeloid and arrested erythroid differentiation and a dramatic increase in
the proliferative and self-renewal capacity of transduced myeloid progenitors.
Thus, TLS-ERG expression alone induced a leukemogenic program that exhibited
similarities to the human disease associated with this translocation. These
results provide an experimental examination of the early stages of the human
leukemogenic process induced by a single oncogene and establish a paradigm to
functionally assay putative leukemogenic genes in normal human hematopoietic
cells.
PMID- 9653172
TI - Propagation and recovery of intact, infectious Epstein-Barr virus from
prokaryotic to human cells.
AB - With current techniques, genetic alterations of herpesviruses are difficult to
perform, mostly because of the large size of their genomes. To solve this
problem, we have designed a system that allows the cloning of any gamma
herpesvirus in Escherichia coli onto an F factor-derived plasmid. Immortalized B
cell lines were readily established with recombinant Epstein-Barr virus (EBV),
demonstrating that the F factor-cloned EBV genome has all the characteristics of
wild-type EBV. Because any genetic modification is possible in E. coli, this
experimental approach opens the way to the genetic analysis of all EBV functions.
Moreover, it is now feasible to generate attenuated EBV strains in vitro such
that vaccine strains can be designed. Because we incorporated the genes for
hygromycin resistance and green fluorescent protein onto the E. coli cloned EBV
genome, the still open question of the EBV target cells other than B lymphocytes
will be addressed.
PMID- 9653173
TI - Autoregulation of thyroid-specific gene transcription by thyroglobulin.
AB - Thyroglobulin (TG), the primary synthetic product of the thyroid, is the
macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage
in follicles, and degradation control thyroid hormone formation and secretion
into the circulation. Thyrotropin (TSH), via its receptor (TSHR), increases
thyroid hormone levels by up-regulating expression of the sodium iodide symporter
(NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the
expression and activity of several thyroid-specific transcription factors,
thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately
regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex class I
gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is
decreased simultaneously. This helps maintain self-tolerance in the face of TSH
increased gene products necessary for thyroid hormone formation. In this report
we show that follicular TG counter-regulates TSH-increased, thyroid-specific gene
transcription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes.
This decreases expression of the TG, TPO, NIS, and TSHR genes, but increases
class I expression. TG acts transcriptionally, targeting, for example, a sequence
within 1.15 kb of the 5' flanking region of TTF-1. TG does not affect ubiquitous
transcription factors regulating TG, TPO, NIS, and/or TSHR gene expression. The
inhibitory effect of TG on gene expression is not duplicated by thyroid hormones
or iodide and may be mediated by a TG-binding protein on the apical membrane. We
hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted
genes is a normal, feedback, compensatory mechanism that limits follicular
function and contributes to follicular heterogeneity.
PMID- 9653174
TI - Evidence for multiclonality in multicentric Kaposi's sarcoma.
AB - Kaposi's sarcoma (KS) develops in a variety of clinical states and is the most
common tumor seen in patients with HIV-1 infection. KS develops as a multifocal
mucocutaneous disease with subsequent spread to visceral organs, and it has been
argued to be a benign proliferation caused by its multifocality at initial
presentation, lack of aneuploidy, and spontaneous regression upon withdrawal of
immunosuppressive agents in iatrogenically induced disease. We wished to
determine whether KS lesions are clonal, indicative of a true neoplasm. Also, we
tested whether multifocal KS lesions are clonally related, derived from a common
progenitor cell or of independent cellular origin. We studied the X-chromosome
inactivation pattern of the human androgen receptor gene in tumor biopsies of
women with KS. This procedure tests for the clonality of a tissue specimen, a
hallmark of neoplasia. Each specimen was microdissected to minimize normal cell
contamination. Of 12 evaluable cases, 10 were HIV-seropositive and 2 were HIV
seronegative. Twenty-four biopsies from the 12 patients were examined. Five cases
were consistent with individual KS lesions being clonal. In two cases, multiple
KS specimens derived from the individual patients had different androgen receptor
alleles inactivated, proving unequivocally that these KS lesions arose
independently from distinct transformed cells. In seven cases, only a polyclonal
pattern of inactivation was observed, whereas two others had tumor areas of both
clonal and polyclonal inactivation patterns. These findings suggest that KS can
be a clonal neoplasm, and in some of the cases multiple KS lesions in a given
patient can arise from independent cellular origins and acquire clonal
characteristics. The polyclonal inactivation pattern observed in other KS lesions
may represent a premalignant stage or false negative results.
PMID- 9653175
TI - Activation of epsilon protein kinase C correlates with a cardioprotective effect
of regular ethanol consumption.
AB - In addition to decreasing the incidence of myocardial infarction, recent
epidemiological data suggest that regular alcohol consumption improves survival
after myocardial infarction. We recently found that chronic ethanol exposure
induces long-term protection against cardiac ischemia-reperfusion injury, which
improves myocardial recovery after infarction. Furthermore, this cardioprotection
by ethanol is mediated through myocyte adenosine A1 receptors. We now determine
the role of protein kinase C (PKC) in ethanol's protective effect against
ischemia-reperfusion injury. Using perfused hearts of ethanol-fed guinea pigs, we
find that improved contractile recovery and creatine kinase release after
ischemia-reperfusion are abolished by PKC inhibition with chelerythrine. Western
blot analysis and immunofluorescence localization demonstrate that regular
ethanol consumption causes sustained translocation (activation) of epsilonPKC,
but not delta or alphaPKC. This same isozyme is directly implicated in ischemic
preconditioning's protection against ischemia-reperfusion injury. Our findings
suggest (i) that regular ethanol consumption induces long-term cardioprotection
through sustained translocation of epsilonPKC and (ii) that PKC activity is
necessary at the time of ischemia to mediate ethanol's protective effect against
ischemia-reperfusion injury. Studying this selective effect of ethanol on
epsilonPKC activation may lead to new therapies to protect against ischemia
reperfusion injury in the heart and other organ systems.
PMID- 9653176
TI - Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants.
AB - The neuroprotective actions of cannabidiol and other cannabinoids were examined
in rat cortical neuron cultures exposed to toxic levels of the excitatory
neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a
nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (
)Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against
neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3
hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D
aspartate receptor-induced toxicity has been shown to be calcium dependent; this
study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic
acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly
mediated by voltage sensitive calcium channels. The neuroprotection observed with
cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating
it to be cannabinoid receptor independent. Previous studies have shown that
glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several
synthetic cannabinoids all were demonstrated to be antioxidants by cyclic
voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced
oxidative damage as well as or better than other antioxidants in a chemical
(Fenton reaction) system and neuronal cultures. Cannabidiol was more protective
against glutamate neurotoxicity than either ascorbate or alpha-tocopherol,
indicating it to be a potent antioxidant. These data also suggest that the
naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a
potentially useful therapeutic agent for the treatment of oxidative neurological
disorders such as cerebral ischemia.
PMID- 9653177
TI - Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular
calcification and stone formation.
AB - Calcium phosphate is deposited in many diseases, but formation mechanisms remain
speculative. Nanobacteria are the smallest cell-walled bacteria, only recently
discovered in human and cow blood and commercial cell culture serum. In this
study, we identified with energy-dispersive x-ray microanalysis and chemical
analysis that all growth phases of nanobacteria produce biogenic apatite on their
cell envelope. Fourier transform IR spectroscopy revealed the mineral as
carbonate apatite. The biomineralization in cell culture media resulted in
biofilms and mineral aggregates closely resembling those found in tissue
calcification and kidney stones. In nanobacteria-infected fibroblasts, electron
microscopy revealed intra- and extracellular acicular crystal deposits, stainable
with von Kossa staining and resembling calcospherules found in pathological
calcification. Previous models for stone formation have led to an hypothesis that
elevated pH due to urease and/or alkaline phosphatase activity is a lithogenic
factor. Our results indicate that carbonate apatite can be formed without these
factors at pH 7.4, at physiological phosphate and calcium concentrations.
Nanobacteria can produce apatite in media mimicking tissue fluids and glomerular
filtrate and provide a unique model for in vitro studies on calcification.
PMID- 9653178
TI - Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and
sustained inhibition of translation initiation mediate the anticancer effects of
clotrimazole.
AB - Regulation of translation initiation plays a critical role in the control of cell
growth and division in eukaryotic cells. Translation of many growth regulatory
proteins including cyclins depends critically on translation initiation factors
because their mRNAs are translated inefficiently. We report that clotrimazole, a
potent antiproliferative agent both in vitro and in vivo, inhibits cell growth by
interfering with translation initiation. In particular, clotrimazole causes a
sustained depletion of intracellular Ca2+ stores, which results in activation of
PKR, phosphorylation of eIF2alpha, and thereby in inhibition of protein synthesis
at the level of translation initiation. Consequently, clotrimazole preferentially
decreases the expression of the growth promoting proteins cyclin A, E and D1,
resulting in inhibition of cyclin-dependent kinase activity and blockage of cell
cycle in G1.
PMID- 9653179
TI - Mutagenesis associated with nitric oxide production in macrophages.
AB - To better understand the mechanisms through which persistent
infections/inflammation increase cancer risks, we assessed the potential
genotoxic properties of NO produced by macrophages. We recently showed that mouse
macrophage RAW264.7 cells were capable of resuming exponential growth after
stimulation for NO production by interferon-gamma (IFN-gamma) and/or
lipopolysaccharide. Here, we report that increases in mutant fraction (MF) in the
endogenous, X-linked, hprt gene of the cells are associated with NO exposure.
Cells stimulated with 100 units/ml IFN-gamma continuously for 14 and 23 days
produced a total of 9.8 and 14 micromol of NO per 10(7) cells, respectively. MFs
in the hprt gene of NO-producing cells were 16.6 and 31.3 x 10(-5), respectively,
compared with 2.2 and 2.5 x 10(-5) in untreated cells. Addition of an NO synthase
inhibitor, N-monomethyl-L-arginine, to the culture medium decreased NO production
and MF by 90% and 85%, respectively. Reverse transcription-PCR and DNA sequencing
revealed that NO-associated hprt mutations did not differ significantly from
those arising spontaneously, with the exception that certain small
deletions/insertions and multiple exon deletions were observed only in the
former. MF also increased significantly in cells stimulated for only 4 days with
lipopolysaccharide plus IFN-gamma for higher rates of NO production. The types
and proportion of hprt mutations induced under these conditions were strikingly
similar to those associated with long-term NO exposure. These results indicate
that NO exposure results in gene mutations in RAW264.7 cells through mechanisms
yet to be identified and may also contribute to spontaneous mutagenesis.
PMID- 9653180
TI - Functional and physical interactions of the ARF tumor suppressor with p53 and
Mdm2.
AB - The INK4a-ARF locus encodes two proteins, p16(INK4a) and p19(ARF), that restrain
cell growth by affecting the functions of the retinoblastoma protein and p53,
respectively. Disruption of this locus by deletions or point mutations is a
common event in human cancer, perhaps second only to the loss of p53. Using
insect cells infected with baculovirus vectors and NIH 3T3 fibroblasts infected
with ARF retrovirus, we determined that mouse p19(ARF) can interact directly with
p53, as well as with the p53 regulator mdm2. ARF can bind p53-DNA complexes, and
it depends upon functional p53 to transcriptionally induce mdm2 and the cyclin
dependent kinase inhibitor p21(Cip1), and to arrest cell proliferation. Binding
of p19(ARF) to p53 requires the ARF N-terminal domain (amino acids 1-62) that is
necessary and sufficient to induce cell cycle arrest. Overexpression of p19(ARF)
in wild type or ARF-null mouse embryo fibroblasts increases the half-life of p53
from 15 to approximately 75 min, correlating with an increased p53-dependent
transcriptional response and growth arrest. Surprisingly, when overexpressed at
supra-physiologic levels after introduction into ARF-null NIH 3T3 cells or mouse
embryo fibroblasts, the p53 protein is handicapped in inducing this checkpoint
response. In this setting, reintroduction of p19(ARF) restores p53's ability to
induce p21(Cip1) and mdm2, implying that, in addition to stabilizing p53, ARF
modulates p53-dependent function through an additional mechanism.
PMID- 9653181
TI - Tissue factor transcription driven by Egr-1 is a critical mechanism of murine
pulmonary fibrin deposition in hypoxia.
AB - Local hypoxemia and stasis trigger thrombosis. We have demonstrated previously
that in a murine model of normobaric hypoxia pulmonary fibrin deposition is a
result of expression of tissue factor, especially in oxygen-deprived mononuclear
phagocytes (MPs). We now show that transcription factor early-growth-response
gene product (Egr-1) is rapidly activated in hypoxia, both in vitro and in vivo,
and is responsible for transcription and expression of tissue factor in hypoxic
lung. MPs and HeLa cells subjected to hypoxia (pO2 approximately 13 torr) had
increased levels of tissue factor transcripts (approximately 18-fold) and an
increased rate of transcription (approximately 15-fold), based on nuclear run-on
analysis. Gel-shift analysis of nuclear extracts from hypoxic MPs and HeLa cells
demonstrated increased DNA-binding activity at the serum response region (SRR;
111/+14 bp) of the tissue factor promoter at Egr-1 motifs. Using 32P-labeled Egr
consensus oligonucleotide, we observed induction of DNA-binding activity in
nuclear extracts from hypoxic lung and HeLa cells because of activation of Egr-1,
by means of supershift analysis. Transient transfection of HeLa cells with
chimeric plasmids containing wild-type or mutant SRR from the tissue factor
promoter showed that intact Sp1 sites are necessary for basal promoter activity,
whereas the integrity of Egr-1 sites was required for hypoxia-enhanced
expression. A central role for Egr-1 in hypoxia-mediated tissue factor expression
was confirmed by experiments with homozygous Egr-1 null mice; wild-type mice
subjected to oxygen deprivation expressed tissue factor and showed fibrin
deposition, but hypoxic homozygous Egr-1 null mice displayed neither tissue
factor nor fibrin. These data delineate a novel biology for hypoxia-induced
fibrin deposition, in which oxygen deprivation-induced activation of Egr-1,
resulting in expression of tissue factor, has an unexpected and central role.
PMID- 9653182
TI - In vivo transfer of barley stripe mosaic hordeivirus ribonucleotides to the 5'
terminus of maize stripe tenuivirus RNAs.
AB - The Tenuivirus maize stripe virus (MStV) shares many properties with viruses in
the genus Phlebovirus of the family Bunyaviridae. Besides genome organization and
gene expression strategies, one property shared by these plant- and vertebrate
infecting viruses is that transcription gives rise to virus-specific mRNAs
containing nonviral 5'-terminal nucleotide sequences. The 5'-terminal nucleotides
are believed to be derived from host mRNA sequences as a result of "cap
snatching." We investigated whether specific nucleotide sequences could serve as
primer donors for cap-snatching in vivo. Barley (Hordeum vulgare) plants were
singly and doubly infected with MStV and the Hordeivirus barley stripe mosaic
virus (BSMV). A reverse transcription-PCR assay was used to identify chimeric
BSMV/MStV RNAs. Specific reverse transcription-PCR products were detected from
doubly infected plants by using one PCR primer corresponding to the 5' termini of
the BSMV RNAs (alpha, beta, and gamma) and a second primer complementary to MStV
RNA 4. The resulting cDNAs were cloned, and nucleotide sequence analysis showed
them to be chimeric, containing BSMV 5'-terminal sequences as well as MStV RNA 4
sequences. All clones contained the BSMV RNA 5' primer nucleotide sequence, but
they also showed characteristics common to Tenuivirus mRNAs. More than 80% of the
clones contained BSMV RNA nucleotides not present on the PCR primer. Several
lacked the exact 5' terminus of MStV RNA 4, a feature also seen for viruses in
the Bunyaviridae. These data show that heterologous virus RNAs (BSMV) can serve
as primer donors for MStV mRNA capped RNA-primed transcription in doubly infected
plants.
PMID- 9653183
TI - Two distinct forms of long-term depression coexist at the mossy fiber-CA3 synapse
in the hippocampus during development.
AB - During a critical period of postnatal development, between postnatal days 6 and
14, a high-frequency stimulation train (100 Hz for 1 s) to the mossy fibers
induces a long-term depression (LTD) of synaptic efficacy of 29 +/- 5.2%. This
form of LTD is homosynaptic. It is independent of the activation of N-methyl-D
aspartate or metabotropic glutamate receptors but needs an increase in calcium
into the postsynaptic cell for its induction. At the same synapse LTD also could
be induced by low-frequency stimulation of the mossy fibers (1 Hz for 15 min). In
this case the magnitude of the depression is 37 +/- 4.2%. This form of LTD is N
methyl-D-aspartate independent but requires the activation of metabotropic
glutamate receptors because it is prevented by (S)-alpha-methyl-4
carboxyphenylglycine (1 mM). Moreover its induction appears to be presynaptic,
because, in contrast with the high-frequency one, it is not blocked by loading
the postsynaptic cell with the calcium chelator EGTA or bis-(-o
aminophenoxy)ethane-N, N,N',N'-tetraacetic acid (BAPTA). Saturation of one form
of LTD does not occlude the other, suggesting that high and low frequency-induced
LTD depend on distinct mechanisms of induction and expression. Quantal (noise
deconvolution) analysis of minimal excitatory postsynaptic potentials shows,
similarly to high-frequency LTD, a decrease in quantal content without any change
in quantal size after low-frequency LTD, suggesting that in both forms of LTD the
site where maintenance mechanisms are located is presynaptic.
PMID- 9653184
TI - Neuroblast pattern formation: regulatory DNA that confers the vnd/NK-2 homeobox
gene pattern on a reporter gene in transgenic lines of Drosophila.
AB - DNA fragments -0.57, -2.2, -2.9, -5.3, and -8.4 kb in length from the upstream
regulatory region of the vnd/NK-2 gene were cloned in the 5'-flanking region of a
beta-galactosidase (beta-gal) reporter gene in the P-element pCaSpeR-AUG-beta
gal, and the effects of the DNA on the pattern and time of expression of beta-gal
were determined in transgenic embryos. Embryos from 11 lines transformed with
8.4 kb of vnd/NK-2 regulatory DNA expressed beta-gal patterns that closely
resemble those of vnd/NK-2. In embryos from four lines transformed with -5.3 kb
of vnd/NK-2 DNA, beta-gal was found in the normal vnd/NK-2 pattern in the nerve
cord but not in part of the cephalic region. beta-Gal patterns in embryos from
transgenic lines containing -0.57, -2.2, or -2.9 kb of vnd/NK-2 DNA did not
resemble vnd/NK-2. Null vnd/NK-2 mutant embryos containing the homozygous P
element p[-8.4 to +0.34 beta-gal] expressed little beta-gal in contrast to
siblings with a wild-type vnd/NK-2 gene. We conclude that (i) the 8.4-kb DNA
fragment from the vnd/NK-2 gene contains the nucleotide sequences required to
generate the normal pattern of vnd/NK-2 gene expression, sequences that may be
involved in the switch between neuroblast vs. epidermoblast pathways of
development, (ii) the 5'-flanking region of the vnd/NK-2 gene between -5.3 and
8. 4 kb is required for vnd/NK-2 gene expression in the most dorsoanterior part
of the cephalic region, and (iii) vnd/NK-2 protein is required, directly or
indirectly, for maintenance of vnd/NK-2 gene expression.
PMID- 9653185
TI - Different patterns of truncated prion protein fragments correlate with distinct
phenotypes in P102L Gerstmann-Straussler-Scheinker disease.
AB - The clinicopathological phenotype of the Gerstmann-Straussler-Scheinker disease
(GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene
(GSS P102L) shows a high heterogeneity. This variability also is observed in
subjects with the same prion protein gene PRNP haplotype and is independent from
the duration of the disease. Immunoblot analysis of brain homogenates from GSS
P102L patients showed two major protease-resistant PrP fragments (PrP-res) with
molecular masses of approximately 21 and 8 kDa, respectively. The 21-kDa
fragment, similar to the PrP-res type 1 described in Creutzfeldt-Jakob disease,
was found in five of the seven subjects and correlated with the presence of
spongiform degeneration and "synaptic" pattern of PrP deposition whereas the 8
kDa fragment, similar to those described in other variants of GSS, was found in
all subjects in brain regions showing PrP-positive multicentric amyloid deposits.
These data further indicate that the neuropathology of prion diseases largely
depends on the type of PrP-res fragment that forms in vivo. Because the formation
of PrP-res fragments of 7-8 kDa with ragged N and C termini is not a feature of
Creutzfeldt-Jakob disease or fatal familial insomnia but appears to be shared by
most GSS subtypes, it may represent a molecular marker for this disorder.
PMID- 9653186
TI - Human autoantibodies specific for the alpha1A calcium channel subunit reduce both
P-type and Q-type calcium currents in cerebellar neurons.
AB - The pharmacological properties of voltage-dependent calcium channel (VDCC)
subtypes appear mainly to be determined by the alpha1 pore-forming subunit but,
whether P-and Q-type VDCCs are encoded by the same alpha1 gene presently is
unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at
motor nerve terminals that underlie muscle weakness in the autoimmune Lambert
Eaton myasthenic syndrome (LEMS). We first studied their action on changes in
intracellular free Ca2+ concentration [Ca2+]i in human embryonic kidney (HEK293)
cell lines expressing different combinations of human recombinant VDCC subunits.
Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent
reduction in the K+-stimulated [Ca2+]i increase in the alpha1A cell line but not
in the alpha1B, alpha1C, alpha1D, and alpha1E cell lines, establishing the
alpha1A subunit as the target for these autoantibodies. Exploiting this
specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and
observed a reduction in P-type current in Purkinje cells and both P- and Q-type
currents in granule cells. These data are consistent with the hypothesis that the
alpha1A gene encodes for the pore-forming subunit of both P-type and Q-type
VDCCs.
PMID- 9653187
TI - Representation of spatial frequency and orientation in the visual cortex.
AB - Knowledge of the response of the primary visual cortex to the various spatial
frequencies and orientations in the visual scene should help us understand the
principles by which the brain recognizes patterns. Current information about the
cortical layout of spatial frequency response is still incomplete because of
difficulties in recording and interpreting adequate data. Here, we report results
from a study of the cat primary visual cortex in which we employed a new image
analysis method that allows improved separation of signal from noise and that we
used to examine the neurooptical response of the primary visual cortex to
drifting sine gratings over a range of orientations and spatial frequencies. We
found that (i) the optical responses to all orientations and spatial frequencies
were well approximated by weighted sums of only two pairs of basis pictures, one
pair for orientation and a different pair for spatial frequency; (ii) the
weightings of the two pictures in each pair were approximately in quadrature (1/4
cycle apart); and (iii) our spatial frequency data revealed a cortical map that
continuously assigns different optimal spatial frequency responses to different
cortical locations over the entire spatial frequency range.
PMID- 9653188
TI - Sequestration of cAMP response element-binding proteins by transcription factor
decoys causes collateral elaboration of regenerating Aplysia motor neuron axons.
AB - Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce
gene expression, which is thought to be a key event for regeneration. Increases
in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a
family of transcription factors that bind to and modulate the expression of CRE
(Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia
motor neurons to examine the role of CRE-binding proteins in axonal regeneration
after injury. We report that axonal injury increases the binding of proteins to a
CRE sequence-containing probe. In addition, Western blot analysis revealed that
the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result
of axonal injury. The sequestration of CRE-binding proteins by microinjection of
CRE sequence-containing plasmids enhanced axon collateral formation (both number
and length) as compared with control plasmid injections. These findings show that
Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors
participates in the regeneration of motor neuron axons.
PMID- 9653189
TI - Synaptic facilitation by reflected action potentials: enhancement of transmission
when nerve impulses reverse direction at axon branch points.
AB - A rapid, reversible enhancement of synaptic transmission from a sensory neuron is
reported and explained by impulses that reverse direction, or reflect, at axon
branch points. In leech mechanosensory neurons, where one can detect reflection
because it is possible simultaneously to study electrical activity in separate
branches, action potentials reflected from branch points within the central
nervous system under physiological conditions. Synapses adjacent to these branch
points were activated twice in rapid succession, first by an impulse arriving
from the periphery and then by its reflection. This fast double-firing
facilitated synaptic transmission, increasing it to more than twice its normal
level. Reflection occurred within a range of resting membrane potentials, and
electrical activity produced by mechanical stimulation changed membrane potential
so as to produce and cease reflection. A compartmental model was used to
investigate how branch-point morphology and electrical activity contribute to
produce reflection. The model shows that mechanisms that hyperpolarize the
membrane so as to impair action potential propagation can increase the range of
structures that can produce reflection. This suggests that reflection is more
likely to occur in other structures where impulses fail, such as in axons and
dendrites in the mammalian brain. In leech sensory neurons, reflection increased
transmission from central synapses only in those axon branches that innervate the
edges of the receptive field in the skin, thereby sharpening spatial contrast.
Reflection thus allows a neuron to amplify synaptic transmission from a selected
group of its branches in a way that can be regulated by electrical activity.
PMID- 9653190
TI - Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal
cytoskeleton.
AB - p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that plays a
central role in the control of mRNA translation. It physiologically
phosphorylates the S6 protein of the 40s ribosomal subunit in response to
mitogenic stimuli and is a downstream component of the rapamycin-sensitive
pathway, which includes the 12-kDa FK506 binding protein and includes rapamycin
and the 12-kDa FK506 binding protein target 1. Here, we report the identification
of neurabin (neural tissue-specific F-actin binding protein), a neuronally
enriched protein of 1,095 amino acids that contains a PDZ domain and binds
p70(S6k). We demonstrate the neurabin-p70(S6k) interaction by yeast two-hybrid
analysis and biochemical techniques. p70(S6k) and neurabin coimmunoprecipitate
from transfected HEK293 cells. Site-directed mutagenesis of neurabin implicates
its PDZ domain in the interaction with p70(S6k), and deletion of the carboxyl
terminal five amino acids of p70(S6k) abrogates the interaction. Cotransfection
of neurabin in HEK293 cells activates p70(S6k) kinase activity. The mRNA of
neurabin and p70(S6k) show striking colocalization in brain sections by in situ
hybridization. Subcellular fractionation of rat brain demonstrates that neurabin
and p70(S6k) both localize to the soluble fraction of synaptosomes. By way of its
PDZ domain, the neuronal-specific neurabin may target p70(S6k) to nerve
terminals.
PMID- 9653191
TI - Normal retina releases a diffusible factor stimulating cone survival in the
retinal degeneration mouse.
AB - The role of cellular interactions in the mechanism of secondary cone
photoreceptor degeneration in inherited retinal degenerations in which the
mutation specifically affects rod photoreceptors was studied. We developed an
organ culture model of whole retinas from 5-week-old mice carrying the retinal
degeneration mutation, which at this age contain few remaining rods and numerous
surviving cones cocultured with primary cultures of mixed cells from postnatal
day 8 normal-sighted mice (C57BL/6) retinas or retinal explants from normal
(C57BL/6) or dystrophic (C3H/He) 5-week-old mice. After 7 days, the numbers of
residual cone photoreceptors were quantified after specific peanut lectin or anti
arrestin antibody labeling by using an unbiased stereological approach.
Examination of organ cultured retinas revealed significantly greater numbers of
surviving cones (15-20%) if cultured in the presence of retinas containing normal
rods as compared with controls or cocultures with rod-deprived retinas. These
data indicate the existence of a diffusible trophic factor released from retinas
containing rod cells and acting on retinas in which only cones are present.
Because cones are responsible for high acuity and color vision, such data could
have important implications not only for eventual therapeutic approaches to human
retinal degenerations but also to define interactions between retinal
photoreceptor types.
PMID- 9653192
TI - Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate
uptake by presynaptic nerve endings in mouse cerebral cortex.
AB - We previously reported that lithium stimulated extracellular glutamate
accumulation in monkey and mouse cerebrocortical slices. We report here that this
is caused by lithium-induced inhibition of glutamate uptake into the slice.
Glutamate release was amplified 5-fold over inhibition of uptake. When the
effects of lithium and the specific glutamate transporter inhibitors, L-trans
pyrrolidine-2, 4-dicarboxylic acid and dihydrokainic acid, were plotted as
glutamate accumulation vs. inhibition of glutamate uptake, the plots were
superimposable. This finding strongly indicates that lithium-induced glutamate
accumulation is caused entirely by inhibition of uptake. With cerebrocortical
synaptosomes, inhibition of glutamate uptake was greater than in slices,
suggesting that presynaptic nerve endings are the primary site of inhibition of
uptake by lithium. Inhibition of uptake was caused by a progressive lowering of
Vmax, as the lithium concentration was increased, whereas the Km remained
constant, indicating that lithium inhibited the capacity of the transporter but
not its affinity. Chronic treatment of mice with lithium, achieving a blood level
of 0.7 mM, which is on the low side of therapeutic, up-regulated synaptosomal
uptake of glutamate. This would be expected to exert an antimanic effect. Lithium
is a mood stabilizer, dampening both the manic and depressive phases of bipolar
disorder. Interestingly, although the uptake of glutamate varied widely in
individual control mice, uptake in lithium-treated mice was stabilized over a
narrow range (variance in controls, 0.423; in lithium treated, 0.184).
PMID- 9653193
TI - Reversal of anticancer multidrug resistance by the ardeemins.
AB - Two "reverse prenyl" hexahydropyrroloindole alkaloids, 5-N-acetylardeemin and 5-N
acetyl-8-demethylardeemin, were evaluated as reversal agents in cells exhibiting
a multidrug resistant (MDR) phenotype. These ardeemins (i) reversed drug
resistance to vinblastine (VBL) or to taxol as much as 700-fold at relatively
noncytotoxic concentrations in vitro; (ii) as a single agent at high
concentrations killed MDR cells more efficaciously than the respective parent
wild-type cells; and (iii) exhibited strong synergistic effects with doxorubicin
(DX) and VBL against the growth of MDR neoplastic cells, and to a lesser extent,
of the parent wild-type cells. Mechanistic studies showed that photoaffinity
labeling of P-glycoprotein (Pgp) with [3H] azidopine was competitively inhibited
by the ardeemins. Resistance to DX in MDR-[Pgp+ and MDR-associated protein
(MRP)+], MDR-Pgp+, lung resistance protein (LRP)+-expressing, and wild-type lung
cancer cells were reversed 110- to 200-fold, 50- to 66-fold, 7- to 15-fold, and
0.9- to 3-fold, respectively, by 20 microM of the ardeemins. Moreover, these
compounds increased the intracellular accumulation of VBL and markedly decreased
its efflux. Finally, in vivo combination studies demonstrated that nontoxic doses
of the ardeemins with DX significantly improved the chemotherapeutic effects in
B6D2F1 mice bearing DX-resistant P388 leukemia, and nude mice bearing human MX-1
mammary carcinoma xenografts. The above features indicate that the ardeemins may
have utility in the therapy of cancer.
PMID- 9653194
TI - The endogenous cannabinoid anandamide inhibits human breast cancer cell
proliferation.
AB - Anandamide was the first brain metabolite shown to act as a ligand of "central"
CB1 cannabinoid receptors. Here we report that the endogenous cannabinoid
potently and selectively inhibits the proliferation of human breast cancer cells
in vitro. Anandamide dose-dependently inhibited the proliferation of MCF-7 and
EFM-19 cells with IC50 values between 0.5 and 1.5 microM and 83-92% maximal
inhibition at 5-10 microM. The proliferation of several other nonmammary tumoral
cell lines was not affected by 10 microM anandamide. The anti-proliferative
effect of anandamide was not due to toxicity or to apoptosis of cells but was
accompanied by a reduction of cells in the S phase of the cell cycle. A stable
analogue of anandamide (R)-methanandamide, another endogenous cannabinoid, 2
arachidonoylglycerol, and the synthetic cannabinoid HU-210 also inhibited EFM-19
cell proliferation, whereas arachidonic acid was much less effective. These
cannabimimetic substances displaced the binding of the selective cannabinoid
agonist [3H]CP 55, 940 to EFM-19 membranes with an order of potency identical to
that observed for the inhibition of EFM-19 cell proliferation. Moreover,
anandamide cytostatic effect was inhibited by the selective CB1 receptor
antagonist SR 141716A. Cell proliferation was arrested by a prolactin mAb and
enhanced by exogenous human prolactin, whose mitogenic action was reverted by
very low (0.1-0.5 microM) doses of anandamide. Anandamide suppressed the levels
of the long form of the prolactin receptor in both EFM-19 and MCF-7 cells, as
well as a typical prolactin-induced response, i.e., the expression of the breast
cancer cell susceptibility gene brca1. These data suggest that anandamide blocks
human breast cancer cell proliferation through CB1-like receptor-mediated
inhibition of endogenous prolactin action at the level of prolactin receptor.
PMID- 9653195
TI - Novel paracrine signaling mechanism in the ocular ciliary epithelium.
AB - The ciliary body contains an epithelial bilayer consisting of an outer pigmented
cell layer (PE) and an inner nonpigmented cell layer (NPE) responsible for
aqueous humor secretion. Secretion may be mediated in part by cytosolic Ca2+
concentration ([Ca2+]i), but whether or how the two layers could coordinate their
Ca2+ signals to regulate secretion is unclear. To investigate interactions
between PE and NPE, we examined [Ca2+]i signaling in isolated intact ciliary
epithelial bilayers using confocal microscopy. Phenylephrine selectively
increased [Ca2+]i in PE and acetylcholine increased [Ca2+]i in NPE, but
epinephrine increased [Ca2+]i in both layers. This increase spread from PE to
NPE, and [Ca2+]i signaling across the bilayer remained coordinated during [Ca2+]i
oscillations. All epinephrine-induced [Ca2+]i signaling was blocked by the alpha1
adrenergic antagonist prazosin, whereas signaling in the NPE but not PE was
blocked by the beta-adrenergic antagonist propranolol, the gap junction blockers
octanol and 18alpha-glycyrrhetinic acid, or the A kinase inhibitor Rp
diastereomer of adenosine 3',5'-cyclic monophosphothioate. The beta-adrenergic
agonist isoproterenol failed to increase Ca2+ by itself, but isoproterenol plus
phenylephrine-induced [Ca2+]i signals across the bilayer similar to those induced
by epinephrine. Finally, isoproterenol increased cell-to-cell spread of lucifer
yellow via gap junctions, whereas cell-to-cell spread of [Ca2+]i signals could be
induced by photorelease of caged inositol 1,4,5-trisphosphate. Thus, calcium
signals are coordinated in the epithelial bilayer so that adrenergic stimulation
can increase [Ca2+]i in NPE, but only if NPE are primed by activation of
endogenous adenylyl cyclase, whereupon they receive stimulation from adjacent PE
via gap junctions. This novel interplay between endocrine and paracrine pathways
may coordinate [Ca2+]i signaling across the ciliary epithelial bilayer.
PMID- 9653196
TI - Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive KATP
channel: molecular cloning, expression and biological properties.
AB - Sulfonylureas are a class of drugs commonly used in the management of non-insulin
dependent diabetes mellitus. Their therapeutic action results primarily from
their ability to inhibit ATP-sensitive potassium (KATP) channels in the plasma
membrane of pancreatic beta cells and thereby stimulate insulin release. A key
question is whether an endogenous ligand for the KATP channel exists that is able
to mimic the inhibitory effects of sulfonylureas. We describe here the cloning of
the cDNA encoding human alpha-endosulfine, a 13-kDa peptide that is a putative
candidate for such a role. alpha-Endosulfine is expressed in a wide range of
tissues including muscle, brain, and endocrine tissues. The recombinant protein
displaces binding of the sulfonylurea [3H]glibenclamide to beta cell membranes,
inhibits cloned KATP channel currents, and stimulates insulin secretion. We
propose that endosulfine is an endogenous regulator of the KATP channel, which
has a key role in the control of insulin release and, more generally, couples
cell metabolism to electrical activity.
PMID- 9653197
TI - Low-temperature carbon utilization is regulated by novel gene activity in the
heart of a hibernating mammal.
AB - Hibernation is a physiological adaptation characterized by dramatic decreases in
heart rate, body temperature, and metabolism, resulting in long-term dormancy.
Hibernating mammals survive for periods up to 6 mo in the absence of food by
minimizing carbohydrate catabolism and using triglyceride stores as their primary
source of fuel. The cellular and molecular mechanisms underlying the changes from
a state of activity to the hibernating state are poorly understood; however, the
selective expression of genes offers one level of control. To address this
problem, we used a differential gene expression screen to identify genes that are
responsible for the physiological characteristics of hibernation in the heart of
the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Here, we
report that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme
4 are up-regulated in the heart during hibernation. Pancreatic lipase is normally
expressed exclusively in the pancreas, but when expressed in the hibernating
heart it liberates fatty acids from triglycerides at temperatures as low as 0
degreesC. Pyruvate dehydrogenase kinase isozyme 4 inhibits carbohydrate oxidation
and depresses metabolism by preventing the conversion of pyruvate to Ac-CoA. The
resulting anaerobic glycolysis and low-temperature lipid catabolism provide
evidence that adaptive changes in cardiac physiology are controlled by the
differential expression of genes during hibernation.
PMID- 9653198
TI - Local mechanical stimulation induces components of the pathogen defense response
in parsley.
AB - Cell suspension cultures of parsley (Petroselinum crispum) have previously been
used as a suitable system for studies of the nonhost resistance response to
Phytophthora sojae. In this study, we replaced the penetrating fungus by local
mechanical stimulation by using a needle of the same diameter as a fungal hypha,
by local application of a structurally defined fungus-derived elicitor, or by a
combination of the two stimuli. Similar to the fungal infection hypha, the local
mechanical stimulus alone induced the translocation of cytoplasm and nucleus to
the site of stimulation, the generation of intracellular reactive oxygen
intermediates (ROI), and the expression of some, but not all, elicitor-responsive
genes. When the elicitor was applied locally to the cell surface without
mechanical stimulation, intracellular ROI also accumulated rapidly, but
morphological changes were not detected. A combination of the mechanical stimulus
with simultaneous application of low doses of elicitor closely simulated early
reactions to fungal infection, including cytoplasmic aggregation, nuclear
migration, and ROI accumulation. By contrast, cytoplasmic rearrangements were
impaired at high elicitor concentrations. Neither papilla formation nor
hypersensitive cell death occurred under the conditions tested. These results
suggest that mechanical stimulation by the invading fungus is responsible for the
observed intracellular rearrangements and may trigger some of the previously
demonstrated changes in the activity of elicitor-responsive genes, whereas
chemical stimulation is required for additional biochemical processes. As yet
unidentified signals may be involved in papilla formation and hypersensitive cell
death.
PMID- 9653199
TI - Glutaredoxin function for the carboxyl-terminal domain of the plant-type 5'
adenylylsulfate reductase.
AB - 5'-Adenylylsulfate (APS) reductase (EC 1.8.99.-) catalyzes the reduction of
activated sulfate to sulfite in plants. The evidence presented here shows that a
domain of the enzyme is a glutathione (GSH)-dependent reductase that functions
similarly to the redox cofactor glutaredoxin. The APR1 cDNA encoding APS
reductase from Arabidopsis thaliana is able to complement the cysteine auxotrophy
of an Escherichia coli cysH [3'-phosphoadenosine-5'-phosphosulfate (PAPS)
reductase] mutant, only if the E. coli strain produces glutathione. The purified
recombinant enzyme (APR1p) can use GSH efficiently as a hydrogen donor in vitro,
showing aKm[GSH] approximately of 0.6 mM. Gene dissection was used to express
separately the regions of APR1p from amino acids 73-327 (the R domain),
homologous with microbial PAPS reductase, and from amino acids 328-465 (the C
domain), homologous with thioredoxin. The R and C domains alone are inactive in
APS reduction, but the activity is partially restored by mixing the two domains.
The C domain shows a number of activities that are typical of E. coli
glutaredoxin rather than thioredoxin. Both the C domain and APR1p are highly
active in GSH-dependent reduction of hydroxyethyldisulfide, cystine, and
dehydroascorbate, showing a Km[GSH] in these assays of approximately 1 mM. The R
domain does not show these activities. The C domain is active in GSH-dependent
reduction of insulin disulfides and ribonucleotide reductase, whereas APR1p and R
domain are inactive. The C domain can substitute for glutaredoxin in vivo as
demonstrated by complementation of an E. coli mutant, underscoring the functional
similarity between the two enzymes.
PMID- 9653200
TI - Inhibition in verbal working memory revealed by brain activation.
AB - There are many occasions in which humans and other animals must inhibit the
production of some behavior or inhibit the processing of some internal
representation. Success in inhibitory processing under normal circumstances can
be revealed by the fact that certain brain pathologies render inhibitory
processing ineffective. These pathologies often have been associated with damage
to frontal cortex, including lateral and inferior aspects. We provide behavioral
evidence of a verbal working memory task that, by hypothesis, engaged inhibitory
processing, and we show (by using positron emission tomograpny) that the
inhibitory processing is associated with a lateral portion of the left prefrontal
cortex. The task in which subjects engaged was item-recognition: Four target
letters were presented for storage followed, after a brief interval, by a probe
letter that could match a target letter or not. On some trials, when the probe
did not match a target letter and therefore required a "no" response, the probe
had matched a target letter of the previous trial, so on these trials a "yes"
response was prepotent and had to be inhibited, by hypothesis. Compared with a
condition in which no prepotent response was created, this condition yielded
brain activation in left inferior frontal gyrus, in the region of Brodmann's area
45.
PMID- 9653201
TI - Health promoting lifestyles: healthy women and women with breast cancer.
PMID- 9653202
TI - Teaching ethics in nursing.
PMID- 9653203
TI - Telehealth in home care practice.
PMID- 9653204
TI - A creative student presentation on the nursing management of a complex family.
PMID- 9653205
TI - Chest tubes: to clamp or not to clamp.
PMID- 9653206
TI - Teach what?: reflections on the transition from hospital teaching to teaching in
the community.
AB - For a nurse educator, the sudden assignment to teaching in the community after
years of hospital teaching and practice can cause distress. While persons with
such experience do not possess the skills to teach the care of aggregate
populations, they can be successful in teaching students to care for patients in
their homes and in other community settings. Participating in on-site
orientation, developing perspectives that recognize patient autonomy and the
significance of family context, and using more discovery learning strategies
enable faculty to achieve course goals and to contribute to curricular goals.
PMID- 9653207
TI - Stress, balloons, and theory.
PMID- 9653208
TI - Nursing students and Haiku.
AB - The emphasis in nursing education is frequently on facts, details, and linear
issues. Students need more encouragement to use the creative abilities which
exist in each of them. The use of haiku, a simple unrhymed Japanese verse, is one
method which stimulates nursing students to use their creativity. A haiku
exercise worked well in encouraging a group of nursing students to express their
feelings.
PMID- 9653209
TI - Strengthening the interdisciplinary education of nurses in violence prevention,
detection, and intervention.
PMID- 9653210
TI - Teaching pathophysiology from a multicultural perspective.
AB - Pathophysiology is the study of deviation from normal physiology and the 70
kilogram white male that remains the standard by which all else is compared. As
United States demographics shift, a new perspective is necessary to meet the
needs of multicultural patients. This article describes how a multicultural
perspective provides a new framework for teaching that both transforms course
content and stimulates new teaching methodologies.
PMID- 9653211
TI - Refinements in the dimensional analysis method of dose calculation problem
solving.
AB - Although the dimensional analysis method for solving dose calculation problems is
gaining acceptance with nurse educators, many inconsistencies in teaching
methodologies remain that can be confusing to both students and practicing
nurses. The author presents refinements to the dimensional analysis method which
can improve speed and accuracy in dose calculations and will be universally
applicable to all types of clinical dosage problems.
PMID- 9653212
TI - A collaborative preceptor model for clinical teaching of beginning nursing
students.
AB - With decreased clinical and faculty resources, monitoring students in the
clinical area for safety and progress can be difficult. The authors discuss a
project that used preceptors for selected beginning students to address issues
related to high student-to-faculty ratios, individualized teaching, role
modeling, and increased faculty time for scholarship. Based on student evaluation
of the pilot project, the authors recommend using nurse preceptors for teaching
beginning nursing students.
PMID- 9653213
TI - Boyer's model of scholarship applied to a career ladder for nontenured nursing
faculty.
AB - This article presents a career ladder for the reappointment and promotion of
nontenured clinical faculty, based on Boyer's model of the scholarship of
teaching, application, discovery, and integration and on his four principles and
six standards. Titles, lengths of appointments, criteria, obligations, and
professional development are defined for four levels of clinical faculty. Guide
questions modeled on Boyer's dimensions of scholarship, principles, and standards
that were used to guide the development of the career ladder are included.
PMID- 9653214
TI - Curriculum restructuring using the practice-based Omaha System.
AB - Nursing programs across the country are reviewing and revising their curricula in
search of the best ways to prepare nursing students for clinical practice in the
21st century. Because of compatibility with healthcare trends, program
philosophy, and university functions, one baccalaureate program chose to organize
curricular content using the structure of the practice-based Omaha System. The
authors share the experiences of this process.
PMID- 9653215
TI - Designing courses for the Internet. A conceptual approach.
AB - One current higher education paradigm shift is the movement from traditional
classroom settings and interactive television satellite transmission to course
and program delivery via the World Wide Web (WWW). The authors describe the
experiences of faculty in reconceptualizing and redesigning course and program
delivery via the Internet. An electronic "template" has been collaboratively
developed by multidisciplinary university partners to facilitate this work. The
template incorporates an advanced nursing practice conceptual framework based on
American Association of Colleges of Nursing (AACN) core educational essentials
for advanced practice combined with a continuum of electronic course tools.
Strategies, tools, and applications are discussed.
PMID- 9653217
TI - Ethical problems in research on families who are abusing children.
AB - Child abuse within the family is a highly sensitive issue and therefore difficult
to research. This article is based on our experiences of a child abuse research
project in Finland. Special attention is given to ethical considerations during
the initiation of the study, and in the sampling procedures, data collection and
reporting. Most importantly, all those taking part in studies on sensitive issues
must be guaranteed full confidentiality and anonymity. There are also other
ethical considerations that go beyond the usual concerns in the research process.
PMID- 9653216
TI - The legal and ethical status of children in health care in the UK.
AB - Ethical issues about children's rights in respect of matters concerning resource
allocation or treatment opportunities are now a matter for public consumption and
concern. Alongside this exists a long-frustrated desire by children's nurses to
promote children's health. Long-held assumptions about the legal and moral status
of children within the health care system in this country are now rightly
scrutinized and challenged. Those of us who claim to represent children now
possess an opportunity to exploit public attention for the benefit of these
children. This article will explore selected major relevant legal and moral
concepts that relate to children with the aim of making transparent some of the
important and often confusing information available. It is anticipated that
debates about the legal and ethical status of children may be stimulated and
fuelled from the following discussion. It is strongly recommended that entering
into dialogue with families and children about their perceived needs will go a
long way towards advancing thoughtful nursing care of individual children, their
families and the general population.
PMID- 9653218
TI - Ethical issues for neonatal nurses.
AB - This article examines the involvement of neonatal nurses in ethical issues,
achieved through a survey of Australian neonatal nurses. The aim was to discover
if nurses were involved in ethical decisions, to examine various categories of
neonates and the concerns that nurses felt about them, and to determine the
extent to which nurses saw themselves as advocates. A response rate of 65% was
achieved from nurses in two states who worked in intensive care and special care
nurseries. The findings show that nurses were more likely to be involved in
clinical decision making than in ethical decision making, showed the greatest
concern for infants who had an uncertain prognosis, and saw themselves as
advocates for their patients. The issues surrounding these findings are examined.
PMID- 9653219
TI - Nurses' attitudes towards developing a do not resuscitate policy in Japan.
AB - Two questionnaire surveys are reported describing the attitudes of 127 Japanese
nurses towards developing a do not resuscitate (DNR) policy. The background
information features the Japanese health care situations: a lack of policies for
end-of-life care decisions; frequent life-prolonging treatments initiated without
the patient's knowledge or consent; ethical dilemmas confronting nurses in
relation to such treatments; and the public's growing concern over end-of-life
care. A hypothetical DNR policy was used in which a health professional asked
patients about their decision regarding DNR. The respondents supported this model
DNR policy as an ideal. However, they noted that this policy was at variance with
Japanese culture. Recommendations for Japanese nurses emerged from the data. In
order to make an impact on end-of-life decision making, nurses should take
culturally appropriate actions: (1) teach patients about their rights; and (2)
work with physicians to provide patients with accurate information about their
condition.
PMID- 9653220
TI - Ethics in health care management: developing an instrument to assess humane
caring.
AB - The care of patients should be professional, human and humane. This is an ethical
issue. The words human (inhimillinen) and humane (ihmislaheinen) have different
meanings in the Finnish language. At Kuopio University Hospital (1200 beds), in
Finland, it was decided to provide patients with professional and humane caring.
Ethical values differ for different groups of people. Therefore humane caring was
assessed by questioning both hospital patients (n = 160) and staff (n = 196). The
data were subjected to content analysis. The result was that the values obtained
for both patients and staff were similar. Five descriptive categories of humane
caring emerged. To discover what kind of caring was provided for patients, the
categories were operationalized into 66 criteria and a questionnaire was drawn up
on the basis of these criteria. The data for evaluation of the quality of caring
were collected from patients (n = 1708). The data were analysed using cross
tabulations and the chi-squared test; sum variables were calculated for the five
standards. The results suggest that special attention should be paid to
vulnerable patient groups (e.g. the elderly and the young). One means of ethical
management is to support our staff to care more humanely by discussing with them
the results of this study, setting standards and criteria for humane caring and
what this means in practice. It is hoped our caring will therefore be more
humane.
PMID- 9653221
TI - Challenges to nursing values in a changing nursing environment.
AB - The aim of this paper is to analyse how the broad context of nursing practice
plays a stimulating and/or a restricting role in the process of ethical caring.
Three areas of special attention are noted. First, on the societal level, some
developments that influence the state of affairs in the caring sector are
indicated. Secondly, concerning the nursing and medical professions, an
interprofessional dialogue based on specific competence is outlined. Thirdly,
there is a discussion of how health care institutions can evolve from a business
undertaking to a pedagogic-moral area where nurses can learn the moral attitudes
that are essential to achieve 'good care'
PMID- 9653222
TI - Practical dignity in caring.
AB - It is difficult to understand the meaning of 'dignity' in human rights, bioethics
and nursing literature because the word is used so vaguely. Unless dignity's
meaning is spelt out it can disappear beneath more tangible priorities. In this
article we define dignity and show how this can help health workers to maintain
the dignity of people in their care.
PMID- 9653223
TI - A charter for ethical research in maternity care: Association for Improvements in
the Maternity Services; the National Childbirth Trust.
PMID- 9653224
TI - Over the past decade RCN Congress has been marked down in government circles as
an event worth avoiding.
PMID- 9653225
TI - US nurses take a stand. In California and New York nurses have taken strike
action against attempts to erode their pay and conditions.
PMID- 9653226
TI - Staying the course. Figures on drop out rates for students and non-registration
after qualification have set alarm bells ringing.
PMID- 9653227
TI - Life at the top. June Girvin's survey examining the experiences of nurse
executives provides a fascinating insight into their thoughts and views.
PMID- 9653228
TI - Prizing equality. Nurses are being encouraged to enter the new NHS Equality
Awards, which aim to reward practice that stops discrimination in the health
service.
PMID- 9653229
TI - In praise of older staff.
PMID- 9653230
TI - Making decisions for patients.
PMID- 9653231
TI - Bully tactics. How can trust bosses combat bullying?
PMID- 9653232
TI - Dress code. Susie Pilling says nurses should lobby for a research--based wound
care pack.
PMID- 9653234
TI - Ringing the changes.
PMID- 9653235
TI - Understanding the language of Parkinson's disease.
PMID- 9653233
TI - Multiskilling: here to stay.
PMID- 9653236
TI - Developing evidence--based care in mental health nursing.
AB - For evidence-based practice to become a reality, its effects must be demonstrated
clearly in the clinical situation. Practitioners must be sen to access, evaluate
and apply research-based evidence in their day-to-day work. In this article, the
author considers how this process could work in mental health nursing.
PMID- 9653237
TI - Treatment of patients with haemochromatosis.
PMID- 9653238
TI - Expanding the nursing profession.
AB - this paper explores the political, economic and demographic developments which
are shaping new nursing practices throughout the world. The authors observe that
these developments are generally seen to challenge traditional models of nursing
and encourage the role of sub-professional support workers.
PMID- 9653239
TI - Assessing and controlling risk.
AB - This article describes the principles of risk assessment in the workplace. It
outlines regulations relating to health and safety at work as they affect
nursing, and goes on to discuss both qualitative and quantitative risk
assessment.
PMID- 9653240
TI - A stranger in your body.
PMID- 9653241
TI - Psychiatric nurses need to face up to the reality of their role.
PMID- 9653242
TI - A chance to make your mark.
PMID- 9653243
TI - Wheelchair users are getting a poor deal.
PMID- 9653244
TI - Nationalism has become a dirty word in the U.K.
PMID- 9653245
TI - Hit squads and chimps?
PMID- 9653246
TI - Changing the face of mental illness.
PMID- 9653247
TI - More nurses, more patients, more work.
PMID- 9653248
TI - All for one.
PMID- 9653249
TI - Male Catheterisation--1.
PMID- 9653250
TI - Workplace well-being.
PMID- 9653251
TI - Scottish solutions.
PMID- 9653253
TI - Courting danger.
PMID- 9653252
TI - Baby talk.
PMID- 9653254
TI - Practice nurses do not practise their skills, they use them to the full for the
good of their patients.
PMID- 9653255
TI - Switching the management of epilepsy to primary care.
PMID- 9653256
TI - Solution-focused therapies.
AB - This is the final part of the psychotherapy series, which has offered an overview
and insight into some of the major talking therapies used by nurses. This series
and extended material is being drawn together by Nursing Times and Phil Barker
for a book on talking therapies. Previous topics covered in the series were:
Psychodynamic psychotherapy, January 14 Humanistic therapies, February 11
Behavioural therapies, March 11 Family and systemic therapies, April 8.
PMID- 9653257
TI - Cleaning up the act.
PMID- 9653259
TI - The missing link.
PMID- 9653258
TI - Cough control.
PMID- 9653260
TI - The inside track.
PMID- 9653261
TI - [Annenheim is different].
PMID- 9653262
TI - ["Friendly hospital"--Korneuburg].
PMID- 9653263
TI - [AIDS units: ghetto or open unit for everyone?].
PMID- 9653264
TI - [Highly active antiretroviral therapy (HAART)].
PMID- 9653265
TI - [Austrian Nursing Society, Salzburg: shortfalls in old age homes are being played
down].
PMID- 9653266
TI - [Professional and relevant points. The professional association as the voice of
health personnel is dealing with the various demands of its members...].
PMID- 9653268
TI - [The fear of infection--myths and facts].
PMID- 9653269
TI - [Psychosocial care of the HIV-positive patient].
PMID- 9653270
TI - [HIV nursing without fear].
PMID- 9653271
TI - The benefits of getting published.
PMID- 9653272
TI - The nasogastric route.
PMID- 9653273
TI - Taking diabetes seriously.
PMID- 9653274
TI - Publishing your work in nursing journals.
AB - Nurses must share their research and experiences with colleagues in order that
areas of practice are debated and improved. Assessing the suitability of a piece
of work for a journal and following simple ground rules will increase the
likelihood of publication.
PMID- 9653275
TI - Nasogastric drug administration.
AB - Nurses working in one trust frequently requested advice on the preparation of
drugs for nasogastric administration, prompting a survey of their knowledge in
this area. As a result, guidelines were prepared to aid nurses and alert them to
potential problems.
PMID- 9653276
TI - Beliefs about diabetes and diabetic complications.
AB - A study of people with non-insulin dependent diabetes found that, generally, they
had a good understanding of its complications although over half believed they
personally were not vulnerable. Non-diabetic subjects had limited knowledge in
this area.
PMID- 9653277
TI - Confidentiality.
PMID- 9653278
TI - Rheumatoid arthritis.
PMID- 9653279
TI - Pre-operative skin preparation.
PMID- 9653280
TI - The tendering process for beds and mattresses.
AB - As increasing numbers of expensive, sophisticated bed and mattress systems become
available, more trusts are negotiating contracts for supply, maintenance and
training. It is important that tissue viability nurses become involved in such
decision-making.
PMID- 9653281
TI - An information strategy for radiotherapy patients.
PMID- 9653282
TI - Fatigue in patients receiving radiotherapy.
AB - The fatigue that may accompany or follow radiotherapy is often overlooked by
health-care staff, yet this side-effect of treatment can cause great distress.
More research into the causes and methods of relieving such symptoms is needed.
PMID- 9653283
TI - Intravascular catheters.
AB - Intravascular catheters are widely used in health care for a range of therapeutic
and diagnostic procedures involving the cardiovascular system. Nurses should be
aware of the different types available and the problems that can arise.
PMID- 9653284
TI - Crossing area and staff boundaries in wound care.
AB - Staff working in hospitals, the community and nursing homes in the Fife area now
meet in a forum to share their knowledge of wound care. The group is
multidisciplinary and members bring experience from a variety of backgrounds.
PMID- 9653286
TI - Community nursing.
PMID- 9653287
TI - District nurses in the spotlight.
PMID- 9653288
TI - Pressure sores in the community.
PMID- 9653289
TI - Handwashing and infection.
PMID- 9653290
TI - Patients' views of the care given by district nurses.
AB - Understanding the actions that make patients feel 'cared for' by district nurses
can help staff tailor their work to meet patients' needs. Patients in one study
felt that a trusting nurse/patient relationship is the basis of good nursing.
PMID- 9653291
TI - Disinfection of latex gloves with ethyl alcohol.
AB - The ability to disinfect latex gloves successfully between procedures would save
time and be cost-effective. An in vitro study examined the efficacy of using an
ethyl alcohol/bactericide compound to disinfect latex gloves contaminated with
five common bacteria.
PMID- 9653292
TI - Advanced airway management.
PMID- 9653293
TI - Pressure sore prevalence in the community.
AB - As increasing numbers of patients are now being nursed in the community it is
important that strategies for the prevention of pressures sores are in place. A
prevalence survey in one trust helped staff to assess their resource needs and
plan care.
PMID- 9653294
TI - High temperature.
PMID- 9653295
TI - Physiological ageing: 1.
PMID- 9653296
TI - Evaluation of a urine chemistry analyser.
AB - Using an automated urine analyser in the ward may improve the accuracy of urine
testing as nurses no longer have to rely on making subjective colour comparisons.
Staff in one urology unit tested an analyser for ease of use, convenience and
practicality.
PMID- 9653297
TI - Access to records.
PMID- 9653298
TI - Urinary catheters for intermittent use.
AB - Intermittent catheterisation is suitable for a range of patients and has a high
level of patient satisfaction. Careful education is required to minimise the risk
of complications and nurses should be aware of the various types of catheter
available.
PMID- 9653299
TI - Venous leg ulcers. Part 1: Aetiology.
AB - A sound knowledge of the physiology of the venous system is necessary to
understand how venous leg ulcers develop. The main risk factors are thrombus
formation and venous incompetence and nurses should be alert to the signs of
these conditions.
PMID- 9653300
TI - [A global approach to health care: the problem of the the patient's wishes].
AB - Doctors and nurses must take into account the patient's point of view. Therefore
it is necessary to have a clear idea of the patient's wishes, as well as of his
position with regard to the disease. This understanding must be integrated in the
treatment and in the strategy of nursing.
PMID- 9653301
TI - [The teaching of diagnostic methodology in nursing schools].
AB - The European and international discussion on Nursing diagnosis let us be aware of
diagnostic methodology in the nurse' work, at the different responsibility
levels. In this article we discuss some problems and objectives related to the
aims of teaching Nursing diagnosis at post basic university Nursing education
level.
PMID- 9653302
TI - [Structures for the international classification of nursing practice].
AB - The following is a walk through the architectural principles behind the
classification of nursing phenomena and of nursing interventions in the Alpha
version of the International Classification for Nursing Practice. While some
architectural principles are common to the two classifications, other principles
are particular to one or the other classification.
PMID- 9653303
TI - [International congress of nurses, 1997. Healthy youth for a better future].
PMID- 9653304
TI - [How can nurses participate in the development of the International
Classification of Nursing Practice (ICNP)].
PMID- 9653305
TI - [Usefulness of psychometric evaluation in the care of psychiatric patients:
evaluation of the Italian version of "Nurses Observation Scale for Inpatient
Observation" (N.O.S.I.S)].
AB - We carried out a validation study of the Italian version of the "Nurses'
Observation Scale for Inpatient Evaluation" (It. v. N.O.S.I.E). The It. v.
N.O.S.I.E. was administered to a heterogeneous department. Factor analysis
revealed six factors underlying the scale structure (Social interest, Neatness,
Irritability, Psychosis, Retardation, Competence): the result is similar to those
of other previously published studies. The It. v. of N.O.S.I.E. can be considered
a valid instrument useful for the nursing staff in the formulation of individual
care plans for inpatients.
PMID- 9653306
TI - [The world of health care and the directives 626/94-242/96 on safety and health
in the workplace. Prevention of risks for workers: who cares for the
caregivers?].
AB - In Italy, the adoption of the EEC Directives on "Safety and hygiene" has brought
into the health structures a revolution that may be summarized in the sentence:
"to take care for people taking care". This kind of approach has had an impact
also on the medicine legislation, with a shift from B. Ramazzini to L. Devoto,
that is from workers' deseases to occupational medicine. In a first time laws
were founded according to an insurance vision; subsequently safety prevailed; in
a third phase safety and prevention were joined together. To day the basic
concept is: prevention, protection and safety. The involved subjects and the
innovative aspects of Dlgs 626/94 and Dlgs 242/96 are the cornerstones of the
olistic vision according to which "to work for health may cause harm to health".
PMID- 9653307
TI - [Professionalism in nursing: difference between theoretical learning and clinical
activity].
AB - There still seems to exist some dichotomy in nursing education between
theoretical achievements and clinical practice, a key moment to verify applied
knowledge and put it into practice. The aim with the present study is to compare
activities considered professionalizing at a theoretical level with activities
being performed during clinical practice. The instrument utilised to collect data
was a questionnaire on nurse-professionalism using a Likert scale. The subject
participating in the study were 3rd year nursing students from three universities
in Rome. The results clearly shows how the theoretical preparation of nurse
students is in contrast with clinical practice performance. The only nursing area
where theory and practice seem to correspond is that of individualised nursing
care, the biggest gap between theory and practice was found concerning research
activities.
PMID- 9653308
TI - [The nursing service at the enterprise: "Ospedale di Circolo e Fondazione Macchi"
in Varese].
AB - The article present the results of a project carried out by a group of four nurse
managers of the Hospital "Ospedale di Circolo Fondazione Macchi" in Varese,
Italy, in order to constitute the "Nursing Service". The Authors have described
the initial situation with the traditional leading nursing roles in the Hospital
(Nursing Officer and Director of the Nursing School) defining the objectives of
the project. The goal of the Service has been identified, the organizational
structure has been chosen and the different line and staff functions described.
The conclusions inform on the current situation and work for the accreditation of
the Service according to the mission of the Hospital managers and the announced
changes in Lombardy health policy.
PMID- 9653309
TI - [Diagnosis-related groups and nursing care: effects on nursing management].
AB - The system of payment by activities, recently established in Italy, is
introducing radical changements into the Italian Health System. This new system,
however, shows some disadvantages that have been yet displayed in the american
experience. It involves a range of consequences both for the work organisation
and for the Nursing management. The present report emphasizes the risks and the
opportunities they present for the Nursing profession.
PMID- 9653310
TI - [Nutritional knowledge of a group of patients in continuous peritoneal dialysis].
AB - The influence of nursing to the patient undergoing peritoneal dialysis is the
focus of the present research report. By monitoring the patients knowledge, we
can understand how nursing teaching influences patient's health and well being.
PMID- 9653311
TI - [Urinary tract infections in patients with catheterization of the bladder].
PMID- 9653312
TI - [From the National Federation of Associations of Nurses and Other Social Health
Workers to the National Federation of Nursing Societies, Motives for a choice].
PMID- 9653313
TI - [The world of health care and the directives 626/94-242/96 on safety and health
in the workplace. Prevention of risks for workers. Who cares for the caregivers?
2].
AB - While the Manual Handling Task is an important source of risk, it is often
disregarded by the nurse profession The data collected both in the scientific
literature and in the research we are presenting here, agree on the belief that a
higher degree of INFORMATION and EDUCATION--as established in the Dlg 626 94)
would reduce the pathologies due to an erroneous manual handling and to the lack
of mechanical facilities.
PMID- 9653314
TI - [Thoughts on nursing, based on observations made in a Rome intensive care unit].
AB - Nursing in an intensive care unit is probably one of the most extreme and
demanding forms of nursing. Here, the nurse is confronted by the highly dependent
patients and the demanding technological forms of treatment associated with them.
The most demanding challenge for the nurse doesn't arise from the technology but
from her dealing with the weak and defenseless party: the patient. Many nurses
argue that their major difficulties are the result of poor working conditions,
with poor staff to patient ratios, and the need to carry out physicians orders
promptly and efficiently. The following article, in focusing on concepts of shame
and authority, reflects on the nurse-patient-doctor relationship and argues that
the challenges that confront the nurse go beyond those of the poor staff to
patient ratio etc. and are indeed tied strongly to the behaviour patterns, and
subsequent patterns of care, as perpetuated by the institutions and often, by the
nurses themselves.
PMID- 9653315
TI - [Bills for nursing legislation].
PMID- 9653317
TI - [University diploma for pediatric nurses: comparing positions, perspectives].
PMID- 9653318
TI - [Nestor Bereciartu, director general of the ROL editions died in Barcelona on the
14 of April 1998] [In Process Citation]
PMID- 9653319
TI - [Diet based on rations. Practical teaching for type II diabetics].
AB - OBJECTIVE: Evaluate an increase in the level of theoretical and practical
knowledge type II diabetics have about diets based on rations. DESIGN:
Prospective Study MATERIAL AND METHODS: 13 Type II diabetics from a rural area
between 45 and 70 years old with a glycosidic hemoglobin greater than 8%. DM
theoretical knowledge test, validated by Campo et al. before and after the
process. Practical exercise about the quantity of carbohydrates patients served
themselves in their meals, before and after the process. RESULTS: Subjects tested
showed improvement in the percentage of correctly answered questions on the
knowledge test, whether computed by sections or globally. Subjects tested chose
foods with a lower quantity of carbohydrates in them. CONCLUSIONS DRAWN BY THE
PANEL OF AUTHORS: Upon completion of this educational procedure, the results were
positive. A practical educational procedure yields more effective results than
does a theoretical procedure in our patients and our medium. Patients
demonstrated a greater level of satisfaction regarding their condition due to an
increased knowledge about their disease and in particular, a better understanding
about their diets.
PMID- 9653320
TI - [Vitamin and mineral requirements in women].
PMID- 9653321
TI - [Factors harmful during the course of pregnancy].
AB - The important repercussions which teratological factors have in perinatal cases
have made it necessary to create methods which detect congenital defects before
birth. By reading this article, nursing professionals should acquire sufficient
basic knowledge about teratogenesis and teratological factors so that they may
then provide women with a correct health education about these topics during
their peri and postconception periods.
PMID- 9653322
TI - [Pulsating pumps in ambulatory chemotherapy].
PMID- 9653323
TI - [Prevention of traffic accidents].
AB - To inform nursing professionals about their role in the prevention of traffic
accidents, a grave health-related problem, is the purpose of this article. To
begin with, factors which can deteriorate one's capacity to drive vehicles, and
over which nursing professionals can intervene, will be presented. These factors
include alcohol, other drugs, medicines, individual morbidity, the factor of
aging and the use of security devices. A special reference will be made about
widely used medicines. Finally the role that a nurse can fulfill will be
explained. This role can be directed to various sections of the general public,
be of varying natures, be exercised with greater or lesser ease, and lastly can
have more or less effect upon those to whom it is destined.
PMID- 9653324
TI - [Nerves of the left lower extremity].
PMID- 9653325
TI - [Risk factors of ischemic cardiopathy. Study of patients hospitalized in a
coronary unit].
AB - The purpose of this study is to determine the knowledge level patients
hospitalized and diagnosed as suffering from ischemic cardiopathia have about
their risk factors by means of an observationally, descriptively and cross
sectionally designed study. This study was carried out in the Coronary Care Unit
at the Vall d'Hebron General Hospital between December 1995 and March 1996. Data
was taken from clinical reports; furthermore, patients involved in the study were
interviewed. Among the results obtained, the following are worth special mention:
57 patients or 47.5% knew about a HTA relationship; 97 patients or 81% knew about
tobacco as a risk factor; 80 patients or 67% were aware of the cholesterol risk
factor; and 58 patients or 48% had information regarding diabetes as a risk
factor. No significant statistical differences were found among known coronary
patients and nondiagnosed-coronary patients regarding their knowledge of risk
factors. Only two-thirds of the study group considered it important to control
their risk factors. Given the importance of knowledge about risk factors, perhaps
this is the time to consider implementing a health educational program for this
segment of the population.
PMID- 9653326
TI - [Enterocutaneous fistula, a problem in nursing].
PMID- 9653327
TI - [Studies on HIV patients].
AB - This article analyzes the data obtained from a series of planned studies run over
a two year period of time by a group of nurses while they carried out a health
education program with HIV positive patients. This was made possible by a grant
from FIS, Health Research and Investigation Fund. Due to the collaboration by
professionals in the Nursing School of the University of Barcelona and the
Bellvitge Hospital, these studies could be under-taken.
PMID- 9653328
TI - [Massive hepatitis C virus infections among citizens of the Valencia community,
needing surgical therapy. Primum non nocere].
PMID- 9653329
TI - [Health habits of health professionals].
AB - The conduct of medical professionals is an important educational point of
reference for the many people who see and know them. Nurses and other medical
workers are often role models in which their daily health habits may be imitated
by their patients, family of friends. With this in mind a study, based on a
previously published work in the United States (Health Practices of Nursing
Students), was performed to determine, first, if the daily habits of nurses are
indeed healthy and adequate to communicate a salubrious lifestyle; second, to see
if this group considers themselves capable and responsible for changing those
unsanitary habits that they do have. Results of the surveys of 125 subject nurses
from the University of Navarra indicate that there is a great amount of
consciousness regarding the danger of most unsanitary habits and the need to
avoid them, although many of them remain firmly entrenched in their daily lives.
The percentage of nurses who felt capable or responsible for changing unhealthy
practices was low (67.5%).
PMID- 9653330
TI - [Drug inhalation therapy. Therapy for patients with respiratory disorders].
AB - We detected a high number of patients suffering from respiratory ailments which
require successive hospital stays due to acute setbacks in their chronic
respiratory ailments. The majority of these patients receive outpatient clinic
treatment based on use of an inhaler. Given the direct relationship between the
correct use of an inhaler and its effectiveness, we designed our project with the
goal to discover the adroitness these patients have with an inhaler. The results
of our study showed that 67% of the patients tested did not correctly use their
inhaler, there by annulling or diminished the effectiveness of its use.
PMID- 9653331
TI - [Nursing diagnosis of risks. Analysis of cost effectiveness].
AB - BACKGROUND: Today, there is a discussion on the importance of the utilization of
the nursing diagnosis: This makes convenient to evaluate the principal two
existing methodological alternatives, that they are: 1) the problems
identification, 2) the diagnoses statement of the NANDA within process nursing.
The study is centered on the risk diagnoses. OBJECT: 1) To know which the two
work methodologies is more effective. 2) To know if exist economic differences.
METHODS: It is accomplished a cohorts study, in a population of user included in
Program of Handicapped. These were studied during a year. RESULTS: In the group
of patients without diagnoses the incidence rate was of 0.64 conversions/person
year), in the group with diagnoses was of 0.22 (p < 0.001). The mean of visits
after that the is made real, in the group with diagnoses was of 0.35, in the
group without diagnoses of 1.69 (p = 0.012). DISCUSSION: The analysis cost
efficiency of the two work methodologies is clearly more favorable for the
methodology than states nursing diagnosis of the taxonomy of the NANDA.
PMID- 9653332
TI - [Free radicals, antioxidants and environmental contamination].
PMID- 9653333
TI - [National Congress of Non-conventional Medicine. Regulation of the study and
exercise of alternative therapies has been reinstated].
PMID- 9653334
TI - [Toledo was the scene of the II meeting of instructors of pediatric nursing. New
lines of investigation in pediatric nursing].
PMID- 9653335
TI - [The 1 unit for primary care of the aged was created in Santa Fe (Granada). The
head of the unit is a nurse].
PMID- 9653336
TI - [Cartilages of the larynx. Anterior view].
PMID- 9653337
TI - [Scorpion stings].
AB - This article begins by describing how Iberian Peninsula scorpion bites poison
humans. Then the only potentially dangerous scorpion species in the peninsula is
identified. Other types of scorpions or those which inhabit other continents are
not included. Once identified, the author describes the characteristics and
effects on the symptoms of this scorpion bite and how to treat and handle a
victim, both at the moment when the victim is bitten and in hospitals.
PMID- 9653338
TI - [Primary care of bedsores. Frequency and characteristics].
AB - INTRODUCTION: The number of patients afflicted by bedsores under the care of a
Primary Health Clinic is not well-known. Nevertheless, it is a pathology directly
related to nursing care and one which causes an important loss in patient's
quality of life; it aggravates and inhibits the cure of other health problems; it
increases suffering and morbidity; and, at the same time, it increases nursing
care time as well as the costs of health care. SUBJECTS AND METHODS: Under a
widerange study carried out during the month of March, 1996, data from homecare
patients suffering from bedsores was collected by means of a registration list
sent to 305 Primary Health Care Clinic nurses in the province. RESULTS: The 177
nurses who responded registered 107 patients with bedsores. 93.45% of these
patients were older than 65. 234 bedsores were recorded. This means 2.19 findings
per patient, 38.03% on heels and 21.79% on trochanters. 36.75% presented
superficial necrosis and 24.36% evidenced profound necrosis. The average reading
on the Norton Scale was 8.65 +/- 3.25 (mean +/- standard deviation).
OBSERVATIONS: The prevalence of Primary Health Care Clinic patients suffering
from bedsores in the province of Cacers during the period studied swings from 4
to 6 patients for every 10,000 inhabitants and this value increases to between 22
and 26 for every 10,000 inhabitants over 65.
PMID- 9653339
TI - [Vitamin and mineral requirements in women (II)].
PMID- 9653340
TI - [Self protection for nurses. Comparative study].
AB - The nursing personnel at the C.H. Xeral-Cies participated in a study of various
types of self-protection methods over two time spans. The hypotheses investigated
were the following: 1. Is there a divergence in the percentage of personnel
vaccinated against hepatitis B?, 2. Is there an increase in the level of
knowledge about universal precautions?, and 3. Is there any improvement in self
protection methods in the latter study? The statistical analysis used has a
variable range of < 0.05. The results indicated significant differences in the
percentage of personnel vaccinated against hepatitis B, in knowledge about
universal precautions, and in the number of accidental punctures reported to the
Preventative Medicine Service.
PMID- 9653341
TI - [Spinal anesthesia. Repercussions on childbirth].
AB - A study was carried out to discover the action of epidural anesthesia on pain, on
the evolution of dilation and expulsion intervals, on the number of surgically
assisted births, and on perinatal morbidity. Some of the most significant results
indicated that with good techniques, pain disappears in all cases; that the
dilating period is significantly shortened with epidural anesthesia, although
there is an increase in instrumental-assisted childbirths. Even though epidural
anesthesia is, as of this writing, the best method available, the ideal pain
reduction method has yet to be discovered. Part of this study was presented
before the National Congress of Midwives and received the "Nuk" Prize.
PMID- 9653342
TI - ["The gardeners of the skin", a comic strip ... for the better understanding of
burns].
PMID- 9653344
TI - [A catheterization kit, radically transforming incontinence].
PMID- 9653343
TI - [Burns of the palm of the hand, treated in ambulatory care].
PMID- 9653345
TI - [Pain and the quality of life].
PMID- 9653346
TI - [Nursing at home].
PMID- 9653347
TI - [The Europe of home care].
PMID- 9653348
TI - [Home care, towards new responsibilities?].
PMID- 9653349
TI - [Hospitalization at home: an alternative to traditional hospitalization].
PMID- 9653350
TI - [Hospitalization at home: the patient's point of view].
PMID- 9653352
TI - [Present and future of hospitalization at home].
PMID- 9653351
TI - [Hospitalization at home: the nurses' point of view].
PMID- 9653353
TI - [Home hospitalization in psychiatry. Care adapted to the patient].
PMID- 9653354
TI - [How to choose a wheelchair].
PMID- 9653355
TI - [Home hospitalization in psychiatry: nurses' testimonies].
PMID- 9653356
TI - [Inservice training: utopia or reality?].
PMID- 9653358
TI - [Professional stress and wear].
PMID- 9653357
TI - [Health in your luggage].
PMID- 9653359
TI - [At the end of the line...].
PMID- 9653360
TI - Management restructuring and care delivery redesign: dealing effectively with
fear.
PMID- 9653361
TI - Financial statement analysis: a continuation.
PMID- 9653363
TI - Management restructuring: options and opportunities.
PMID- 9653362
TI - Restructuring: make certain you change everything?
PMID- 9653364
TI - Management restructuring: the process of change.
AB - This article provides simple, direct "how to" process steps for nursing leaders
and managers who sense the need to move toward a flattened, decentralized model
as a nursing organizational structure, but are not certain how to get there. The
process of organizational restructuring is fraught with difficulty, but for
health care to be responsive to patients and staff, nurse leaders must take on
the challenge. Principles and process steps that lead to a restructuring plan are
outlined, as well as pitfalls to avoid.
PMID- 9653365
TI - Navigating the barrier reef: QEE to successful restructuring.
AB - This article chronicles the barriers encountered as a multidisciplinary
department undertook management restructuring. Barriers that are addressed
include lack of a sense of urgency; confusion and fear regarding the changing
roles of both staff and managers; insufficient development of coaching skills;
and lack of alignment of performance appraisals, outcomes, and rewards. Insights
gained and strategies to deal with these barriers are discussed.
PMID- 9653366
TI - Point-of-service teams: a leadership opportunity.
AB - To welcome the transitions in management and leadership roles, a leader may
consider developing the skills necessary to promote the success of
interdisciplinary point-of-service teams. The author discusses factors that
contribute to success in leading a point-of-service team. Key strategies and
leader behaviors are addressed. A case study describing one point-of-service team
for patient care redesign is presented and analyzed. The experience was viewed
very positively by the leaders of the team; opportunities for further improvement
are offered.
PMID- 9653367
TI - Personal reflections on early learning in shared leadership.
AB - Shared leadership involves a process as well as a structure. Two key principles
apply to all forms of shared leadership: a commitment to true partnership and a
decision-making structure that allows for balance of power. In this article, the
author shares her personal experience of facilitating a shared leadership model
for staff on a unit level and also an executive model of shared leadership. The
executive model was implemented during a transition after a traditional nursing
leadership position was vacated. Lessons learned in facilitating a staff shared
leadership model and participating in an executive model are discussed and
contrasted. Relationships, dialogue, partnership, and an understanding of
boundaries are essential elements for successful implementation of shared
leadership at any level.
PMID- 9653368
TI - Values-based leadership and organizational development during restructuring.
AB - This article highlights the importance of value-based leadership and cultural
change, and illustrates how organizational development strategies can facilitate
positive learning environments. This is essential during periods of rapid change,
restructuring, and downsizing, when the quality of patient care can be at risk.
By ensuring a values focus, and a systematic approach to the development of a
"learning organization", nurses can be empowered to develop their clinical
practice and to lead the redesign of healthcare systems in a more creative and
patient-centered way.
PMID- 9653369
TI - Seeing down the road: restructuring the work of leadership.
AB - Understanding our own patterns of thought and interaction is one of the
disciplines that can help nurse leaders move from a reactive and retrospective
stance to becoming proactive. A familiar example, driving, illustrates this
concept and applies these principles by suggesting practical ways that we can
model the future for those we lead. We may not be able to totally control the
obstacles along the way, but by staying fixed on the values of stewardship and
service to our patients and staff, we can help draw the map of the future of
health care.
PMID- 9653370
TI - [The best gift is life].
PMID- 9653371
TI - [Abortion].
PMID- 9653372
TI - [Psychological effects of abortion].
PMID- 9653373
TI - [An order of nurses? From myth to reality].
PMID- 9653374
TI - [Poisoning with Amanita phalloides mushrooms. Nursing care].
PMID- 9653375
TI - [Standards and principles of nursing].
PMID- 9653376
TI - [Decline in male fertility: a fatality?].
PMID- 9653378
TI - [The higher school of nursing of the Franciscan Missionaries].
PMID- 9653377
TI - [Therapeutic touch].
PMID- 9653379
TI - [From certification to accreditation].
PMID- 9653380
TI - [An instrument for quality improvement and the evaluation of competence].
PMID- 9653381
TI - [Stakes for nursing services].
PMID- 9653382
TI - [From the project Nursing Care to accreditation. The search for quality. Pathway
of action].
PMID- 9653383
TI - [A pre-accreditation step. The University Hospital Center].
PMID- 9653384
TI - [The National Agency for Accreditation and Health Care Evaluation].
PMID- 9653385
TI - [The Regional Hospitalization Agency and the accreditation of health facilities].
PMID- 9653386
TI - [What is newly politically correct].
PMID- 9653387
TI - [Preparation for the entrance examinations for schools for paramedics].
PMID- 9653388
TI - [Functions of the psychiatric staff nurse].
PMID- 9653389
TI - [Open letter to the Minister of Health].
PMID- 9653390
TI - [Towards a general mobilisation of the profession].
PMID- 9653391
TI - [A national order of nurses: a legal bill shows the consensus of the principal
associations].
PMID- 9653392
TI - [The unity of the nursing profession is in danger. Interview with Christiane
Vanderkam and Sylviane Hocher from the National Group for the mobilization in
psychiatric nursing].
PMID- 9653393
TI - Do large schools really supply more teachers?
PMID- 9653394
TI - Improving the NRMP board: why not direct representation? National Resident
Matching Program.
PMID- 9653395
TI - Enduring strengths of academic medical centers.
PMID- 9653396
TI - An autopsy-reporting system in an internal medicine residency program.
PMID- 9653397
TI - Evaluating the curriculum with standardized patients.
PMID- 9653398
TI - The need for true informed consent in pediatric teaching hospitals.
PMID- 9653399
TI - Challenges to effective medical school leadership: perspectives of 22 current and
former deans.
AB - A persistent decline in the average tenure of medical school deans and a concern
about the implications for medical school leadership led the Council of Deans of
the Association of American Medical Colleges to commission the 1996-1997 study
reported here. The author conducted open-ended interviews with a broad spectrum
of 22 current and former deans, selected to achieve an appropriate distribution
with regard to key characteristics of their schools and to assure the relevance
of the findings to a broad range of settings. His in-depth analysis of the
transcribed interviews, using standard qualitative techniques, was designed to
illuminate the challenges confronting deans and suggest strategies to address
them. The respondents consistently identified two forces in the health care
environment that had had profound impacts on their role as deans and that
frequently posed conflicts between the clinical and educational enterprises: a
decline in the resources available to medical schools following an era of
abundance, and unprecedented competition in the clinical arena. Analysis of their
accounts of the problems they encountered in managing in this changed environment
revealed several underlying sources: imbalance between the breadth of their
responsibilities and their authority to manage; lack of clarity in the dean's
mandate; inadequate institutional support for pursuing the missions of the
school; insufficient attention to identifying requisite expertise and abilities
for effective performance on the job as dean; and an anachronistic search
process. The respondents offered numerous recommendations for addressing these
problems, reflecting optimism about the prospects for purposeful change. While
medical schools have unique features among educational institutions, the author
concludes that the challenges that deans face and the strategies proposed for
addressing them promise to have substantial relevance for academic leadership in
other settings.
PMID- 9653400
TI - Organizational, financial, and environmental factors influencing deans' tenure.
AB - At a time when continuity of leadership in medical schools is most crucial, the
tenures of deans continue to decrease. In the present study of factors
influencing the tenures of 382 U.S. medical school deans from 1985 to 1994, the
authors focused on issues that were likely to have had a greater impact on deans'
tenures in recent years. They assumed that longer tenures are associated with
less complex organizational factors and more stable environmental factors.
Conversely, they assumed that deans and their tenures are adversely affected by
an institution's declining financial health, a complex organizational structure,
and a changing clinical marketplace where there is rapid growth of managed care.
The authors compared the relationships between these factors and the length of
deans' tenures during the ten-year period studied. Among the most important
findings were the fact that schools that were less healthy financially, that had
the same owner as the primary teaching hospital, and that had smaller numbers of
faculty tended to have shorter dean's tenures and higher turnovers of deans.
While the reason for shorter tenures of deans at schools that are less
financially healthy is understandable, the effect of common ownership of the
school and teaching hospital is less obvious, but perhaps the greater
preoccupation of deans with the clinical enterprise in that circumstance is a
significant constraint. The authors hope that the insights from their findings
will be useful to future candidates for deanships in their negotiations with
university officials and will help all parties reach more explicit agreements on
such issues as expectations for financial performance of the medical school and
the roles and relationships of the dean and the teaching hospital director.
PMID- 9653401
TI - The dean as spiritual leader.
AB - These are hard times for medical school deans--high turnover among deans, the
fiscal distress of many medical schools, the gap between what deans expect the
job will be and what is required of them, the stark differences between what the
job of dean is today and what it was in the past, and the threats to the academic
missions of education and research. Using stories, anecdotes, and parables, the
authors illustrates how these very difficulties might be an opportunity to
rethink the role of deans and to re-examine the attributes and skills required of
successful deans today. The ultimate goals of medical education have not changed,
but the drastic nature of the changes taking place all around, and within,
medical education make it more critical than ever to keep in mind what is really
important. Deans must be exquisitely attuned to what is really important and they
must make sure that the academic medical community never loses sight of what that
is. To do that, deans must be deeply rooted personally in the enduring values and
commitments that inform medicine as a profession and a vocation and in the
fundamental values of medical education and scholarship; they must personify and
embody these values; and they must remind us of these values and inspire us to
embrace them and be guided by them. This is the sense in which deans must be
"spiritual" leaders--that is, through their personal example, they must rekindle
and engage the spirit of those working on behalf of the academic mission. While
the need for fiscal expertise, management skills, and diplomatic and
interpersonal skills in deans is widely acknowledged, the need for sensitivity to
the spiritual dimensions of the work of deans has not received the attention it
deserves.
PMID- 9653402
TI - Leading among leaders: the dean in today's medical school.
AB - The magnitude and pace of change in the health care environment demand that
medical schools change. Leading in a time of great change is difficult, and it is
ironic that just when stability in leadership is most needed, the average tenure
of deans is dropping. Indeed, the path to leadership in academic medicine is
strewn with inherent ironies, paradoxes, and idiosyncrasies. For example, few
people who become leaders in academic medicine aspire to, plan for, or seek
training for leadership, yet leadership skills are essential to meet today's
complex institutional demands. Also, most medical school deans were once medical
students, and were selected and trained to be assertive, independent physicians,
not to collaborate. For faculty, the medical school environment traditionally
values individual autonomy and rewards individual achievement, not behavior that
supports a larger community interest. Yet today's deans must be skilled at
collaborative behavior, since they must have a vision for their schools and find
ways to offer direction to the faculty and others to realize that vision. The
author offers ideas about leadership and its development, and stresses that good
leaders must above all curtail their egos in order to do what is best for their
institutions. What a dean does as an individual is not nearly as important as
what a dean enables others to do. The author also provides a checklist of dean's
characteristics and responsibilities to help deans-to-be understand the job and
current deans to think about how to succeed and thrive. He concluded by
reiterating that the culture of individual faculty success based on individual
entrepreneurism is passe. To operate in the new collaborative culture, today's
successful dean must meld persuasion with educational statesmanship, always
informed by a vision of how the school can prosper and serve.
PMID- 9653403
TI - Reflections on the medical deanship.
AB - In 35 years, being dean of a medical school has changed dramatically. Thirty
years ago, the dean's world was still the medical school and its affiliated
hospitals, but soon this world was transformed by new emphasis on research (and
the resources to conduct it) and the increase of specialty medicine. The medical
school became larger and the affiliated hospital more complex. They consolidated
into the modern academic medical center, which then became more diverse and self
contained and eventually became an island of special expertise and achievement in
medicine, the biomedical sciences, and clinical care. Fifteen years, ago, the
academic medical center began to be transformed again, this time by its
competition with or incorporation into managed care and other health care
delivery systems. The medical school dean now operates in an environment far
different from that of the 1960s. Deans spend 90% of their time on five major
issues: too few resources, isolation and division of activity within the
institution, poor management, excessive traditionalism, and too few people with
too much to do. In addressing these issues, the dean has several powerful levers,
including the appointment and promotion of faculty, appointments to committees
and task forces, assignments of budget and space, and controlling the agenda and
leading the debate in the institution. Another but less tangible issue is the
dean's attitude. Another but less tangible issue is the dean's attitude, which
has enormous impact on what happens at the medical school and in its programs.
The deanship will continue but in the new context of a health care delivery
system-with variations on the same five problems and with the same ten levers
available to address them. The responsibility is old; only the context is new.
PMID- 9653404
TI - Ideals in action: the U.S. Schweitzer Fellows Programs.
AB - The inclusion of formal courses in medical ethics as part of standard
undergraduate medical education has not led to widespread confidence in the moral
and professional development of young physicians. As important as classes on
informed consent and other such topics are, alternative approaches to
professional moral development are needed. One example can be found in The U.S.
Schweitzer Fellows Programs, which now support over 100 health professions
students annually in six locations. Fellows participate in activities designed to
strengthen the ideals that originally attracted them to medicine and other health
care fields. Because Dr. Schweitzer is remembered primarily for the way he
translated his ideals of human service into action, the core activity of each
program is a direct-service project that addresses an important unmet health need
of the local community or individuals in the community, with the support of
community-based and school-based mentors. Alumni of these programs report that
their experiences as Schweitzer fellows have helped them integrate their own
ideals into their professional and career development. Such systematic efforts to
recognize and support the latent idealism of young health professionals may
strengthen the moral dimensions of professional life in ways that have broad
social benefits.
PMID- 9653405
TI - Considering primary care in Japan.
AB - Involved in global competition and with a rapidly aging population, Japan is
experiencing major reform in its medical care system and medical education
system. Although compulsory national health insurance and accessibility to
medical care are supported by the overwhelming majority of the Japanese people,
rapidly increasing medical costs have been an important problem. The Japanese
government is in the midst of changing the health insurance system from fee-for
service to capitation, and it moved in the 1980s to reduce the number of new
physicians as a way to control expenditures. With the lessening of government
regulation in the 1990s, each medical school has begun to revise its curriculum
to cope with the increasing amount of medical information available and to
promote efficient learning. Because postgraduate clinical training programs with
defined, comprehensive curricula are rare, and because virtually all clinical
training is in inpatient settings, Japanese physicians' clinical competence tends
to be insufficient for providing first-class community-based primary care. Japan
must try to develop effective education systems in order to deliver better and
more efficient medical care, especially primary care.
PMID- 9653406
TI - Requiring students to have computers: questions for consideration.
AB - For the past several years a dialogue has been taking place in the offices,
lounges, and meeting rooms of medical schools about whether medical students
should be required to bring or purchase computers when they enter school.
Microcomputers offer educators a unique opportunity to provide students with
access to computer-assisted instruction, asynchronous communication, and
extensive knowledge bases. However, there is still no evidence attesting to the
effectiveness of computers as teaching or learning tools in medical education.
The author raises questions that schools need to consider before requiring
students to own computers: What kind of computer best suits their needs? What
might impede using computers to teach? And who is currently requiring computers?
In addressing the last question, the author presents information about 15 North
American schools that currently require their students to have computers,
reporting each school's software and hardware requirements; how each expects
students to use the computers; and who covers the cost of the computers (the
students or the school). Finally, he argues that major institutional commitment
is needed for computers to be successfully integrated into any medical school
curriculum.
PMID- 9653407
TI - What students say about learning and teaching in longitudinal ambulatory primary
care clerkships: a multi-institutional study.
AB - PURPOSE: Ambulatory primary care clerkships have become crucial elements in
medical education. Although most such clerkships employ a block-rotation format,
an alternative longitudinal approach has been developed. This study examines
students' perceptions of learning and instruction occurring during longitudinal
ambulatory clerkships. METHOD: Characteristics of longitudinal ambulatory primary
care clerkships at five medical schools are described. Responses of 429 medical
students to a standardized survey administered at these institutions are analyzed
to ascertain perceptions of learning and teaching occurring during longitudinal
ambulatory clerkship experiences. RESULTS: Enhancements of interpersonal
communication and clinical skills were perceived to be the most positive learning
attributes of the longitudinal ambulatory clerkships. No advantage was discerned
with respect to disease-pattern recognition or generation of differential
diagnoses. While significant inter-institutional variation was present,
particularly with respect to instructional format, there was notable agreement
regarding several aspects of clerkship-related learning and the adequacy of
faculty supervision. CONCLUSION: Students perceived that learning during
longitudinal ambulatory clerkships had greater impact on skill enhancement than
on attainment of knowledge-related objectives. Sources of variation in student
opinion, perceptions of learning as a function of career preference, and
correlation of students' perceptions of learning to demonstrable changes in their
competence require further investigation.
PMID- 9653408
TI - Factorial validation of a widely disseminated educational framework for
evaluating clinical teachers.
AB - PURPOSE: To examine an instrument for evaluating clinical teaching using factor
analysis and to refine the validated instrument to a practical length. METHOD:
Factor analysis on a split sample of 1,581 student evaluations rating 178
teachers. The instrument was based on the seven-category Stanford Faculty
Development Program's (SFDP's) clinical teaching framework and contained 58
Likert-scaled items, with at least seven items per category plus five items
measuring "teacher's knowledge." Standard methodology for survey item reduction
was used to remove items with low or complex factor loadings and iteratively
remove items with low item-scale correlation. Results were replicated on the
second sample. RESULTS: The seven original categories emerged and items
originally categorized under "knowledge" statistically combined with "promoting
self-directed learning." Over 73% of the variance was explained. Item reduction
resulted in 25 items with overall internal consistency over .97 and internal
consistency of constructs ranging from .82 to .95. CONCLUSIONS: Factor analysis
of student ratings validated the seven-category SFDP framework. An abbreviated
instrument to measure the seven categories is described. Results suggest that
students may not systematically distinguish between their teachers' knowledge and
their teachers' ability to promote self-directed learning, an important finding
for both administrators and faculty development programs.
PMID- 9653409
TI - A prospective randomized trial of a residents-as-teachers training program.
AB - PURPOSE: To develop, implement, and evaluate a course for improving the teaching
skills of surgery residents. METHOD: Responses from residents at four general
surgery training programs to a needs assessment survey were used to develop a two
day course for improving teaching skills. Residents at two surgical training
programs were randomly assigned to experimental and control groups, and
experimental residents participated in and evaluated the newly devised course.
Six to seven months later, experimental and control residents' teaching
performances were evaluated using a five-station objective structured teaching
evaluation (OSTE). Differences between the residents' performances were
calculated using Mann-Whitney U, chi-square analysis, or Fisher's exact test.
RESULTS: Participating residents rated the course highly. They considered the
interactive nature of the course its greatest strength. As measured by the OSTE,
the performances of the residents differed least significantly in the feedback
station, where the residents in the experimental groups showed significant
improvement on only one of seven items at one institution, and only one of nine
items at the other. The greatest differences occurred in the microskills teaching
station, where the residents at one institution performed significantly better
than did their control counterparts on four of five items and in overall
performance. CONCLUSION: This study demonstrates the value of a needs assessment
in developing a course to improve residents' teaching skills. Such courses must
provide active learning with opportunities for practicing skills and, following
the course, ongoing feedback to maintain changes in teaching behaviors. The
curriculum developed in this study has been put into a transportable form that
includes an instructor's manual providing guidelines and suggestions for
implementation.
PMID- 9653410
TI - A pilot study of faculty development for basic science teachers.
AB - PURPOSE: Relatively little research has focused on faculty development methods
that assist basic science teachers to improve their instructional skills. This
study was designed to assess the effectiveness for basic science faculty of a
faculty development seminar series that had been previously shown useful for
clinical teachers. METHOD: The Stanford Faculty Development Program's seminars on
clinical teaching were adapted for basic science instruction. Eight pathology
faculty participated in a series of nine small-group seminars designed to provide
teachers with knowledge of a framework for analyzing teaching and identifying
areas for improvement, and skill-based training in specific teaching behaviors.
Each seminar included (1) brief lectures, (2) review of videotaped reenactments
of teaching interactions, (3) role-play exercises with videotape review, and (4)
formulation of personal and departmental teaching goals. RESULTS: Program
evaluation included multiple measures: participant self-assessment, student
ratings of the participants, and blinded ratings of pre- and post-seminar
videotapes of participants' classroom teaching. All measures indicated a positive
effect of the intervention. CONCLUSION: Faculty development programs have
significant potential to enhance basic science instructors' teaching
effectiveness.
PMID- 9653411
TI - Evaluation of primary care futures: a faculty development program for community
health center preceptors.
AB - PURPOSE: To assess the impact of a national series of faculty development
workshops for community health center preceptors. METHOD: Two hundred and twenty
three community health center preceptors from a variety of disciplines attended
one of five workshops conducted in different regions of the country. The
workshops emphasized active learning using role-play to provide skills in
educational planning, teaching styles, evaluation, and feedback. The preceptors
were evaluated before and immediately after the workshop, and again three months
later. They were also asked to assess the quality of the workshop. RESULTS: The
preceptors demonstrated significant increases in the use of five of seven
teaching concepts while analyzing a role-play interaction. In addition, there
were significant positive, immediate changes in familiarity with nine of 11
concepts, which were retained for at least three months. The preceptors also
reported that they continued to use six of the effective teaching behaviors they
had learned three months after the workshop. They were extremely positive in
their assessments of the workshops. CONCLUSION: This preliminary study suggests
that preceptors from a variety of backgrounds can improve their teaching
knowledge and skills by participating in a brief faculty development program that
emphasizes active learning.
PMID- 9653412
TI - Women in orthopedic surgery residencies in the United States.
AB - PURPOSE: To evaluate the effect that increased numbers of women medical school
graduates have had on the composition of orthopedic surgery residencies, and to
evaluate trends over time in the likelihood of women medical students to select
orthopedic residencies. METHOD: The author analyzed JAMA's "Reports on Graduate
and Undergraduate Medical Education" for the years 1977 to 1996, calculating the
numbers of women and men in orthopedic surgery and other surgery residencies, and
medical school composition. RESULTS: Although there have been modest gains in the
number of women in orthopedic surgery training programs in the United States,
women continue to choose orthopedics only one-seventh as often as do men.
CONCLUSION: Orthopedics remains an unattractive career choice for women medical
students compared with their men counterparts. Biases and stereotypes about women
and about orthopedic surgery may account for this difference.
PMID- 9653413
TI - Knowledge of and attitude toward patient confidentiality within three family
medicine teaching units.
AB - PURPOSE: To describe the knowledge and attitudes about confidentiality issues
within family medicine teaching units (FMUs) at McGill University. METHOD: The
authors surveyed McGill University FMU staff (physicians, nurses, and support
staff) on their knowledge of and attitudes toward confidentiality issues.
RESULTS: The response rate was 84%. Only one of nine questions on confidentiality
laws was correctly answered by more than 80% of the respondents. Only 55% of the
support staff knew that police are not permitted free access to charts, although
the majority of those who answered incorrectly held attitudes that were
consistent with the law. Only approximately 25% knew that physicians and nurses
are not permitted free access to any medical record within the center. There were
minimal differences between the professions or between the FMUs. CONCLUSION:
These findings suggest that FMU staff do not fully understand their obligations
towards patient confidentiality.
PMID- 9653414
TI - New bottles for vintage wines: the changing management of the medical school
faculty.
AB - Medical schools are being challenged to develop innovative mechanisms of faculty
governance and management that enlist faculty in meeting the demands of a
competitive marketplace. The authors describe some of these mechanisms in this
article, which is the result of case studies made in 1997 of ten schools.
Measures to increase the accountability of faculty to the strategic directions of
the school include having appointment letters that specify explicitly the roles
and responsibilities of the faculty member, conducting annual performance reviews
based upon more objective criteria, tying salary to performance, lengthening the
pre-tenure probation period, instituting post-tenure review, and redefining the
salary guarantees of tenured faculty. Equally important is balancing these
policies with initiatives to strengthen the accountability of schools to their
faculty. Improved methods of communication between administrators and faculty and
more efficient processes to enable faculty to participate in decision making are
appearing. Formal approaches to mentoring and faculty development are being
implemented. Recognition and reward programs are being strengthened. Alternatives
to tenure are being developed in recognition of the need for increasingly diverse
roles of faculty and to ensure job security. The reengineering of the processes
that will lead to shared vision and accountability will require massive cultural
change. The realization of these goals is likely to depend on the skill of
medical school managers and the ability and willingness of faculty members to
work collaboratively and creatively in designing new methods to accomplish old
missions. Next month's AAMC Paper will explore changes in the structure and
management of medical schools and their owned or closely affiliated facilities to
improve the efficiency of achieving their core missions.
PMID- 9653415
TI - Oppositional defiant disorder symptomatology after traumatic brain injury: a
prospective study.
AB - Our goal was to prospectively study the course of oppositional defiant disorder
(ODD) symptomatology in children and adolescents in the first 2 years after
traumatic brain injury (TBI). Fifty children aged 6 to 14, hospitalized after
TBI, were assessed soon after TBI regarding injury severity; preinjury
psychiatric, socioeconomic, family functioning, and family psychiatric history
status; and neuroimaging was analyzed. ODD symptomatology in the first year after
TBI was related to preinjury family function, social class, and preinjury ODD
symptomatology. Increased severity of TBI predicted ODD symptomatology 2 years
after injury. Change (from before TBI) in ODD symptomatology at 6, 12, and 24
months after TBI was influenced by socioeconomic status. Only at 2 years after
injury was severity of injury a predictor of change in ODD symptomatology. The
influence of psychosocial factors appears greater than severity of injury in
accounting for ODD symptomatology and change in such symptomatology in the first
but not the second year after TBI in children and adolescents. This appears
related to persistence of new ODD symptomatology after more serious TBI.
PMID- 9653416
TI - Acute stress disorder after mild traumatic brain injury.
AB - The debate continues over whether a posttraumatic response occurs in those who
have sustained a traumatic brain injury (TBI). The aim of this study was to
investigate the incidence of acute stress disorder (ASD) in the mild TBI
population. Patients who sustained a mild TBI after a motor vehicle accident (N =
79) were assessed for the presence of ASD. ASD was diagnosed in 13.9% of
patients, and 5.1% were diagnosed with subsyndromal ASD. Dissociative,
reexperiencing, and avoidance symptoms were found to have moderate to high
predictive power. This study highlights the significant number of patients who
experience an acute trauma response after TBI and raises the possibility that
those with ASD denote those for whom an early intervention may prevent longer
term psychopathology. Diagnostic difficulties in defining ASD after TBI are
discussed.
PMID- 9653417
TI - The relationships between premilitary school record data and risk for
posttraumatic stress disorder among Vietnam war veterans.
AB - The purpose of this study was to determine whether Vietnam veterans' risk for
posttraumatic stress disorder (PTSD) was correlated with their premilitary school
performance. The authors compared both primary and secondary school record data
on hospitalized chemically dependent PTSD patients with those of both non-PTSD,
chemically dependent and community controls. All participants were male Vietnam
war combat veterans. The comparisons were made with MANCOVA analyses with the
effects of combat and age differences between groups controlled. For the most
part, primary-school grade point average, absenteeism, and tardiness data on
three groups did not differ significantly. However, the mean secondary school
grade points of the future PTSD patients were generally substantially lower than
those of controls. Additionally, more secondary school absenteeism and tardiness
were reported among future PTSD patients than in the controls. The groups did not
differ significantly on number of extracurricular activities. Academic weakness,
absenteeism, and tardiness in secondary school appear to be moderately strong
predictors of vulnerability to PTSD after traumatization. It also supports the
claim that chronic PTSD is, in part, the result of weaknesses present before
exposure to trauma.
PMID- 9653418
TI - Twin study of dissociative experience.
AB - The relative influence of genetic and environmental influences on measures of
pathological and nonpathological dissociative experience was estimated using a
classic twin-study design. Subjects were 177 monozygotic and 152 dizygotic
volunteer general population twin pairs who completed two measures of
dissociative capacity identified from the items comprising the Dissociative
Experiences Scale (DES). Additive genetic influences accounted for 48% and 55% of
the variance in scales measuring pathological and nonpathological dissociative
experience, respectively. Heritability estimates did not differ by gender. The
genetic correlation between these measures was estimated at .91, suggesting
common genetic factors underlying pathological and nonpathological dissociative
capacity. Genetic and environmental correlations between the DES scales and
measures of personality disorder traits (Dimensional Assessment of Personality
Pathology-Basic Questionnaire; DAPP-BQ) were also estimated. Significant genetic
correlations (median = .38) were found between the DES scales and DAPP-BQ
cognitive dysregulation, affective lability, and suspiciousness, suggesting that
the genetic factors underlying particular aspects of personality disorder also
influence dissociative capacity.
PMID- 9653419
TI - Axis II pathology in outpatients with dissociative identity disorder.
AB - Forty-two outpatients with dissociative identity disorder (DID) and 16
outpatients with dissociative disorder not otherwise specified (DDNOS) were
administered the Millon Clinical Multiaxial Inventory-II (MCMI-II), the Minnesota
Multiphasic Personality Inventory-2 (MMPI-2), and the Dissociative Experiences
Scale (DES). DID patients manifested severe personality pathology (BR > 84) on a
mean of 4.0 MCMI-II scales: avoidant (76%), self-defeating (68%), borderline
(53%), and passive-aggressive (45%). DDNOS cases had severe personality pathology
on fewer MCMI-II scales (mean = 1.69): avoidant (50%) and self-defeating (31%).
The DID and DDNOS groups differed in their scores on the DES (means = 54.9 vs.
25.9), the PK-PTSD scale of the MMPI-2 (means = 33.6 vs. 21.7), and in the
incidence of severe borderline pathology (53% vs. 6%). These data on personality
pathology in DID patients are virtually identical to those of seven previous
studies of personality pathology in chronic PTSD patients (i.e., avoidant, self
defeating, borderline, and passive-aggressive). Such robust convergence of
findings supports the construct validity of DID as a form of posttraumatic
disorder and suggests that there is a quite predictable personologic core to the
clinical picture of severely traumatized individuals.
PMID- 9653420
TI - Remission and relapse in schizophrenia: the Madras Longitudinal Study.
AB - This paper uses monthly symptom data on 90 first-onset schizophrenics in Madras,
India, to characterize, in a continuous manner, the course of remission and
relapse. Remission from the first episode occurs in about 6 months and in about 3
months for later episodes. Syndromes from the Present State Exam, assessed at the
first episode, predict differentially to early and later parts of the course.
Hypomania and simple depression predict early remission from the first episode;
flat affect and grandiose delusions predict longer episodes and shorter
remissions later in the course.
PMID- 9653421
TI - Causal mechanisms of subjective cognitive dysfunction in schizophrenic and
depressed patients.
AB - We examined causal mechanisms of subjective cognitive (dis)abilities in
schizophrenic and depressed patients, and in patient and normal control groups.
This exploratory study included objective cognitive performance (Continuous
Performance Task) as well as mood and mental effort ratings. Self-report of
cognitive dysfunction in patients was not correlated with objective cognitive
deficits. Correlational patterns differed between groups. Our findings in
schizophrenic and depressed patients point to different causal mechanisms of
their subjective cognitive malaise, despite similar subjective ratings. Depressed
patients associate high mental effort during task performance with a reduced
cognitive efficacy, whereas schizophrenic patients associate high effort with
cognitive symptoms like distractibility and overload.
PMID- 9653422
TI - The effects of interviewer gender in mental health interviews.
AB - Despite indications that gender can affect the disclosure of personal
information, few studies examine the effects of interviewer gender in eliciting
information pertaining to psychological functioning and mental health. Analysis
of data collected at the Los Angeles site of the Epidemiological Catchment Area
Study reveals that interviewer gender is significantly related to respondents'
reports of psychiatric symptoms. Male and female respondents interviewed by women
report more symptoms of depression, substance abuse, and conduct disorders than
respondents interviewed by men. It is suggested that female interviewers may
create conditions more conducive to disclosure and be perceived as more
sympathetic than male interviewers. Although limitations of both data and
analysis preclude a definitive conclusion, the findings suggest that interviewer
gender may influence disclosure in mental health and related types of interviews.
PMID- 9653423
TI - Expressed emotion and locus of control.
AB - Expressed emotion is a robust and reliable predictor of psychiatric relapse
across a range of psychopathological conditions and diagnoses. Theoretical
speculation about the expressed emotion construct has suggested that high levels
of criticism in relatives might be linked to attributions and beliefs about the
patient's ability to control his or her symptoms or problem behaviors. Although
there is some empirical support for this notion, no study to date has examined
relatives' beliefs about their own abilities to control problem situations. This
study compared high- and low-critical relatives of patients with schizophrenia on
a measure of locus of control. Consistent with prediction, the locus of control
scores of high-critical relatives were indicative of a more internal locus of
control, whereas those of the low-critical relatives were indicative of a more
external locus of control.
PMID- 9653424
TI - Ginkgo biloba for dementia.
PMID- 9653425
TI - A new rabies vaccine.
PMID- 9653426
TI - Rituximab for non-Hodgkins lymphoma.
PMID- 9653427
TI - Cryptococcal pneumonia complicating pregnancy.
AB - In the present report we describe 4 previously healthy women who developed
cryptococcal pneumonia during pregnancy, and 1 pregnant woman with cryptococcal
meningitis. These cases illustrate a previously uncharacterized spectrum of
cryptococcal disease. We also discuss 24 patients previously reported who had
cryptococcal meningitis during pregnancy. Finally, we review the available data
for each therapeutic option and present an algorithm for management based on
appraisals of disease severity and risk to the unborn fetus. This report
emphasizes the need for heightened awareness of cryptococcosis in the
differential diagnosis of pneumonia, chest pain, and hypoxemia in the pregnant
patient, but at present, there are insufficient epidemiologic data to determine
whether incidences of pulmonary or disseminated cryptococcosis actually increase
during pregnancy. The risk of congenital cryptococcosis to the unborn fetus is
low, and the most likely mechanism whereby neonates acquire invasive fungal
pulmonary infection is through aspiration. While it is unclear whether there is
any real increased risk of spontaneous abortion or premature labor, the data
indicate that overall fetal outcome depends on effective treatment of maternal
infection. For patients with dense air-space consolidation, progressive pulmonary
disease, or dissemination, antifungal therapy is necessary. Optimal treatment is
determined by the acuity and severity of the clinical presentation. Amphotericin
B (approximately 1 g) with or without flucytosine represents the choice for
initial treatment of the more acutely ill patient with disseminated or
progressive pulmonary cryptococcosis who requires hospitalization (whether during
or after pregnancy). Oral fluconazole appears to be safe and effective
alternative therapy after delivery for the less severely ill patient who can be
managed on an outpatient basis. While the use of fluconazole during pregnancy
generally appears safe in terms of fetal outcome (49, 58), the class C status and
single report of fetal malformation (62) preclude confident recommendation for
its use during pregnancy. The risks and benefits of this effective and generally
less toxic drug should be discussed with the parents and weighed against the use
of amphotericin B. For pregnant women with limited pulmonary cryptococcosis
(segmental or nodular infiltrates) and no evidence of dissemination, we recommend
close follow-up without antifungal therapy similar to the recommendation for
normal hosts with minimal disease. However, it is important to note that there is
no extensive experience upon which to base this recommendation for pregnant
individuals (45, 55, 103, 108). It is prudent to use frequent physical
examinations (for example, every 1-2 months), combined with chest roentgenograms
and serum cryptococcal antigens to monitor progression and/or development of
disease in both the mother and child for approximately 6 months postpartum. In
conclusion, cryptococcosis during pregnancy presents a special challenge to the
clinician. A balanced therapeutic approach holds great promise for successful
maternal and fetal outcomes.
PMID- 9653428
TI - Respiratory involvement in relapsing polychondritis. Clinical, functional,
endoscopic, and radiographic evaluations.
AB - Although respiratory involvement occurs in 50% of patients with relapsing
polychondritis (RP) and augurs a poor prognosis, few previous studies have
provided complete descriptions of respiratory tract involvement. For this reason,
we investigated the respective role of clinical, functional, endoscopic, and
radiographic (computed tomography [CT]) examinations in 9 consecutive patients
with RP and lower respiratory tract localization. All exhibited cough, dyspnea,
and wheezing. Eight had a nonreversible obstructive pattern with a marked
decrease of the maximal flow ratio at 75% and 25% of vital capacity. Rotman
functional criteria were evaluated to differentiate upper from lower respiratory
tract involvement; they were consistent with the results of other examinations in
4/9 cases. Endoscopic examination showed moderate to severe inflammation in 8/9
patients; tracheal stenosis was present in 6/9 patients, bronchial stenosis in
4/9 patients, and tracheal collapse in 7 cases. CT showed tracheal stenosis in
8/9 patients (diffuse, 7; localized, 1) and bronchial stenosis in 6/9 patients.
Tracheobronchial wall thickening and/or calcifications were observed in 7 cases.
Clinical symptoms are of poor specificity for defining respiratory involvement
precisely, although degree of dyspnea is correlated to the decrease in forced
expiratory volume in 1 second (FEV1). Functional criteria were helpful in
evaluating the obstructive ventilatory defect but did not differentiate, in most
cases, the respective part of lower and upper respiratory involvement when using
Rotman criteria. Compared to CT findings, endoscopic examination failed to
identify tracheal and bronchial stenosis and tracheal wall alterations at an
early stage of the disease. In our series CT appears to be a reliable method to
identify tracheal and bronchial involvement and can be repeated safely during the
course of the disease.
PMID- 9653429
TI - Septic arthritis of the glenohumeral joint. A report of 11 cases and review of
the literature.
AB - Eleven cases (6 adults and 5 pediatrics) of shoulder septic arthritis are
described, and the English literature from 1960 to 1997 reviewed, for a total of
168 cases. Shoulder septic arthritis is an uncommon and difficult diagnosis
requiring a high index of suspicion and early evaluation of the affected shoulder
by the clinician. The disease usually involves very young infants or elderly
patients (65-75 years old). Associated medical conditions were identified in 60%
of the patients and include systemic disorders such as liver diseases,
alcoholism, and malignancies in 46%; preceding chronic arthritic disorders in
24%; and associated infectious focus in 13% of the patients. Associated
infections were more prevalent in the pediatric population. Intravenous drug
abuse appears not to constitute a major risk factor; it was identified in less
than 5% of patients. All patients presented with acute shoulder ache or with
exacerbation of existing chronic pain in joints previously damaged. Elevated body
temperature (over 38 degrees C) appeared in 67% of the adult patients and in over
90% of the pediatric patients. Shoulder arthritis was frequently accompanied by
an accelerated erythrocyte sedimentation rate that may rise above 100 mm/hr.
Increased white blood cell count was found in approximately 40% of patients. The
initial X-rays were frequently normal, while ultrasonography supported the
diagnosis in some cases by demonstrating accumulation of fluid inside the joint
space. Aspiration of synovial fluid from the affected glenohumeral joint was
necessary to evaluate the offending pathogen. False-negative Gram stain appeared
in approximately 90% of the patients, whereas synovial fluid cultures
demonstrated the pathogen in 88% of patients. Blood cultures were positive in 50%
of adult patients and 90% of pediatric patients. The most common isolated
pathogen was Staphylococcus aureus, which accounted for 41% of infections. Gram
negative bacilli, which accounted for about 20% of infections, are more prevalent
in the pediatric population, especially the neonates. Pyogenic shoulder arthritis
should first be treated with intravenous antibiotics, effective at least against
staphylococcal infections, until the organisms and sensitivities are identified.
Duration of antibiotic therapy should be 3-6 weeks. Unfortunately, our experience
in addition to the literature summary does not allow statistical analysis and
firm conclusions concerning the best therapeutic approach. However, it appears
that in the adult population an operative draining procedure is preferred,
whereas in the pediatric population, a closed needle aspiration, if needed at
all, is the optimal treatment. With prompt antibiotic therapy and drainage of the
shoulder, the patient can be expected to improve clinically, with no serious long
term debilitating effects from the disease.
PMID- 9653430
TI - Invasive aspergillosis. Clinical features of 35 proven cases at a single
institution.
AB - Thirty-five patients with clinical features and histologically or
microbiologically proven infection met predetermined stringent criteria for
invasive aspergillosis over a 5-year period at our institution. Underlying
conditions included hematologic malignancy, solid tumor, bone marrow and solid
organ transplantation, and immunosuppressive therapy. The majority of patients
(94%) presented with respiratory symptoms and abnormal pulmonary chest
radiography; only 40% had neutropenia at time of infection. Invasive
aspergillosis was suspected in only 21 cases (60%). Concomitant infections were
present in 83% of patients. Half of patients had pathogenic or potentially
pathogenic microorganisms other than Aspergillus spp. isolated from pulmonary
specimens at time of aspergillosis. Aspergillus spp. were recovered from sputum
in 75% of patients and from bronchoalveolar lavage in only 52%. Invasive
aspergillosis is an unexpectedly unrecognized disease with poor outcome; overall
mortality was 94% in our series. The lack of sensitivity of diagnostic
procedures, together with the high frequency of concomitant infections, delays
the time of diagnosis. Early diagnostic tests are needed, and presumptive
antifungal therapy among high-risk patients is mandatory.
PMID- 9653432
TI - Breast cancer susceptibility genes. BRCA1 and BRCA2.
AB - Mutations in the BRCA1 and BRCA2 genes lead to an increased susceptibility to
breast, ovarian, and other cancers. It is estimated that 3%-8% of all women with
breast cancer will be found to carry a mutation in 1 of these genes. Families
with multiple affected first-degree relatives and patients with early-onset
disease have been found to harbor mutations at a higher frequency. The BRCA1 and
BRCA2 genes code for large proteins that bear no resemblance to other known
genes. In the cell, they appear to act as tumor suppressor genes and play a role
in the maintenance of genome integrity, although the precise function of these
genes has yet to be discovered. A large number of distinct mutations have been
found in cancer families around the world. The majority of the defined pathologic
mutations result in premature truncation of the protein (frameshift and nonsense
mutations). These mutations may substantially increase the risk for breast and
ovarian cancer, but a precise risk estimate for each different mutation cannot be
determined. Depending on the familial context, the risk of breast cancer
associated with carrying a mutation has been estimated to range from 50% to 85%.
The role of these genes in sporadic cancer remains unknown. Patients and
physicians considering BRCA1 and BRCA2 genetic testing are faced with a difficult
decision. The diversity of mutations and lack of general population data prevent
accurate risk prediction. This is further complicated by the paucity of data on
effective prevention strategies for those identified at higher risk. Thus, the
nature of clinical testing for BRCA1 and BRCA2 continues to present challenges
that reinforce the necessity of personal choice within the context of thorough
genetic counseling.
PMID- 9653431
TI - Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50
patients.
AB - We analyzed the clinical and laboratory characteristics of 50 patients with
catastrophic antiphospholipid syndrome (APS) (5 from our clinics and 45 from a
MEDLINE computer-assisted review of the literature from 1992 through 1996).
Thirty-three (66%) patients were female and 17 (34%) were male. Twenty-eight
(56%) patients had primary APS, 15 (30%) had defined systemic lupus erythematosus
(SLE), 6 (12%) had "lupus-like" syndrome, and 1 (2%) had rheumatoid arthritis.
Mean age of patients in this series was 38 +/- 14 years (range, 11-74 yr). Three
(6%) patients developed the clinical picture of catastrophic APS under the age of
15 years, and 11 (22%) were 50 years old or more. In 11 (22%) patients,
precipitating factors contributed to the development of catastrophic APS
(infections in 3, drugs in 3, minor surgical procedures in 3, anticoagulation
withdrawal in 2, and hysterectomy in 1). The presentation of the acute multi
organ failure was usually complex, involving multiple organs simultaneously or in
a very short period of time. The majority of patients manifested microangiopathy-
that is, occlusive vascular disease affecting predominantly small vessels of
organs, particularly kidney, lungs, brain, heart, and liver--with a minority of
patients experiencing only large vessel occlusions. Thrombocytopenia was reported
in 34 (68%) patients, hemolytic anemia in 13 (26%), disseminated intravascular
coagulation in 14 (28%), and schistocytes in 7 (14%). The following antibodies
were detected: lupus anticoagulant (94%), anticardiolipin antibodies (94%), anti
dsDNA (87% of patients with SLE), antinuclear antibodies (58%), anti-Ro/SS-A
(8%), anti-RNP (8%), and anti-La/SS-B (2%). Anticoagulation was used in 70% of
the patients, steroids in 70%, plasmapheresis in 40%, cyclophosphamide in 34%,
intravenous gammaglobulins in 16%, and splenectomy in 4%. Most patients, however,
received a combination of nonsurgical therapies. Death occurred in 25 of the 50
(50%) patients. In most, cardiac problems seemed to be the major cause of death.
In several of these, respiratory failure was also present, usually due to acute
respiratory distress syndrome and diffuse alveolar hemorrhage. Among the 20
patients who received the combination of anticoagulation, steroids, and
plasmapheresis or intravenous gammaglobulins, recovery occurred in 14 (70%)
patients. The use of ancrod and defibrotide appeared to be effective in the 2
respective patients in whom they were used.
PMID- 9653433
TI - New ways to ventilate newborns in acute respiratory failure.
AB - Out treatment options for acute neonatal failure have expanded greatly in the
last 20 to 30 years. This article reviews patient-triggered ventilation, high
frequency ventilation, negative extrathoracic pressure ventilation, nitric oxide
therapy, liquid ventilation, extracorporeal membrane oxygenation, and advances in
pulmonary function monitoring. The authors present background theories, describe
equipment, review clinical strategies, and the results of recent trials.
PMID- 9653434
TI - Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update.
AB - Over the past 5 years, increasing understanding about the pathophysiology of
meconium-stained amniotic fluid (MSAF) and the meconium aspiration syndrome (MAS)
has occurred. Many new therapies are being used in an attempt to prevent MAS and
to treat the disorder. The authors review the current status of knowledge
concerning the MSAF and MAS and management of these entities.
PMID- 9653435
TI - The use of inhaled nitric oxide in a wide variety of clinical problems.
AB - Inhaled nitric oxide (NO) clearly decreased pulmonary vascular resistance in
pediatric patients with pulmonary hypertension, regardless of the underlying
origin of the pulmonary hypertension. In persistent pulmonary hypertension of the
neonate (PPHN) and CHD, the use of inhaled NO appears to improve the outcome of
these patients. In acute respiratory distress syndrome (ARDS) and surfactant
deficiency the role of inhaled NO therapy remains unclear. The use of inhaled NO
is safe in a carefully monitored setting with a delivery system designed to
minimize the generation of NO2.
PMID- 9653436
TI - Surfactant replacement therapy. An update on applications.
AB - Surfactant replacement therapy has been shown to be an effective and often life
saving treatment for newborn infants with respiratory distress syndrome (RDS).
This article provides the clinician with an update regarding the various other
applications of surfactant replacement therapy, as well as issues related to
surfactant administration for the preparations approved for use in pediatric
patients.
PMID- 9653437
TI - Bronchopulmonary dysplasia. Impact of surfactant replacement therapy.
AB - Bronchopulmonary dysplasia is a major contributor to the morbidity and mortality
of infants born prematurely. Surfactant replacement therapy has had a significant
impact on the death rate from respiratory distress syndrome, yet the impact on
bronchopulmonary dysplasia is minimal. Despite these findings, the overall
incidence and severity of bronchopulmonary dysplasia are likely to decline over
time as neonatal care continues to advance.
PMID- 9653438
TI - Neonatal cardiopulmonary resuscitation: the good news and the bad.
AB - Many health care professionals all over the world have been taught neonatal
cardiopulmonary resuscitation (CPR) using the neonatal CPR course based upon the
work of Bloom and Cropley. The purpose of this article is to provide a
retrospective review of the development of some of the neonatal CPR techniques,
to discuss current techniques and to complement the dedication of this issue to
Dr. Ronald Brown and Catherine Copley, MN, RN.
PMID- 9653439
TI - Advances in fetal surgery.
AB - The use of maternal/fetal ultrasound screening has become commonplace in today's
society. The principle behind fetal surgery evolves around the potential of
correction or interruption of various abnormal processes that may bring about
fetal demise or can become life-threatening to the newborn. This article reviews
the progressive technical improvements and advances in fetal surgery.
PMID- 9653440
TI - Advances in neonatal surgery.
AB - Neonatal surgery has reached a high degree of sophistication. We are now entering
a new era of widespread screening of the unborn by means of ultrasound, with
planned intrauterine, intrapartum, and immediate postpartum interventions. Many
pediatric surgical centers are now focusing their investigative efforts on
elucidating the cellular, molecular, and biochemical response to disease and
therapeutic agents. The author presents the topic of neonatal surgery to some of
the newer applications, techniques, and approaches.
PMID- 9653441
TI - Future financial neonatal shock.
AB - In a changing economic climate, the neonatologist must be aware of all of the
forces that can affect the practice of neonatology. In addition to clinical
issues, billing and reimbursement must take into account physician work and
common procedural terminology (CPT) codes, which accurately describe the medical
services and procedures delivered. An understanding of this coding and resource
based work unit system is necessary to prevent financial loss. The influence of
managed care, capitation, fixed per-case reimbursement, practice guidelines and
care maps have already seriously affected clinical practice patterns. The
neonatologist must be proactive in negotiating contracts using historic
information and outcome data to define and defend the quality of care provided.
PMID- 9653442
TI - Permanent presence of managed care and outcome of critically ill infants.
AB - In the era of managed care, the potential for high-risk patients of all ages to
receive less than optimal care exists because the mechanism for reimbursement is
designed to promote savings. The specific ways managed care payment mechanisms
actually differ from indemnity insurance or fee-for-service are conceptually
quite simple. This article reviews mechanisms such as utilization review, setting
length-of-stay bench marks, preapproval for referrals to specialists, specific
treatments, procedures, and hospital days.
PMID- 9653443
TI - Principles of disease management in neonatology.
AB - This article emphasizes the emerging facets of disease-management practice that
impact directly on establishing a measured care system that can produce the
information needed to establish a continuous quality improvement program. The
areas discussed are risk assessment, clinical management guidelines and
carepaths, and the measurement of system output known as clinical outcomes. The
remainder of the article details the aspects of risk assessment, guideline
function, and outcome assessment, critical in a disease-managed measured care
system.
PMID- 9653444
TI - Developmental outcome in very low birthweight infants. Current status and future
trends.
AB - Surfactant therapy has significantly reduced mortality, but not morbidity, in the
very low birthweight (VLBW) infant. Questions persist as to the edge of
viability, the allocation of health care resources for the VLBW infant, and
whether or not we are improving survival at the cost of contributing more
handicapped individuals to society. Since surfactant alone has not reduced
morbidity, other medical and behavioral treatments are being studied that may
help to optimize neurodevelopmental outcome in the VLBW infant.
PMID- 9653445
TI - The death of a baby in the infant special care unit.
AB - We are learning about the meaning of the death of an infant, and its impact on
the family. We are becoming aware that by being there, health care staff become
important in how the life-long process of grieving will get started. Educational
and supportive practices for staff and programs for bereaved family members that
set the stage for healthy grieving are difficult but valuable in the work of
neonatal intensive care.
PMID- 9653446
TI - Caring for the graduate from the neonatal intensive care unit. At home, in the
office, and in the community.
AB - This article focuses on recent progress in the understanding of optimal care for
the neonatal intensive care unit (NICU) graduate in three domains that have
relevance to primary care pediatricians: the concept of developmentally
supportive care for the immature central nervous system of fragile premature
infants; an understanding of the function and systems of community-based early
intervention available for medically complex, developmentally challenged and at
risk infants; and the management of technology-dependent children at home.
PMID- 9653447
TI - Mammalian base excision repair and DNA polymerase beta.
PMID- 9653448
TI - Database of mouse strains carrying targeted mutations in genes affecting cellular
responses to DNA damage. Version 2.
PMID- 9653449
TI - Repair of cyclobutane pyrimidine dimers in the O6-methylguanine-DNA
methyltransferase (MGMT) gene of MGMT proficient and deficient human cell lines
and comparison with the repair of other genes and a repressed X-chromosomal
locus.
AB - We studied the repair of cyclobutane pyrimidine dimers (CPDs) in the 5' terminal
part of the transcriptionally inactive O6-methylguanine-DNA methyltransferase
(MGMT) gene of MGMT-deficient human cell lines (A172, A-253 and WI-38 VA13) and
in a proficient cell line (HaCaT), in which the MGMT gene was transcribed. Repair
rates in the MGMT gene were compared with those in the active uracil-DNA
glycosylase (UNG) and c-myc genes, and those in the repressed X-linked 754 locus
and the RNA polymerase I-transcribed ribosomal gene cluster. In the active MGMT
gene, there was a distinct strand specificity with more repair in the template
(transcribed) strand (TS) than in the non-template strand (NTS). In contrast, no
apparent strand bias in the repair of CPDs was observed in the inactive MGMT gene
in the MGMT deficient cell lines, although the rates of repair varied between
different cell lines. Repair in the inactive MGMT gene was consistently lower
than repair in the NTSs of the expressed genes, and approached the generally poor
repair of the repressed 754 locus. Whereas repair in the UNG gene was strand
specific in HaCaT, A-172 and WI-38 VA13 cells, no clear strand bias in repair of
this gene was evident in A253 cells and repair was relatively inefficient.
Although the repair kinetics was essentially similar in the two strands of the c
myc gene in all cell lines examined, the rate and extent of repair were in
general significant, probably due to an observed transcription of both strands in
the c-myc region. In conclusion, our results indicate that the relative rates of
repair in inactive MGMT genes are comparable to those of repressed loci and are
lower than repair rates in the NTSs of active genes, but the absolute rate of
repair varies between different transformed cells.
PMID- 9653450
TI - Mechanisms determining sensitivity to cisplatin in three mutant Chinese hamster
ovary cell lines.
AB - To gain insight into factors determining the response of tumours to cisplatin, we
studied pathways involved in resistance to cisplatin: drug uptake, cytoplasmic
detoxification and DNA repair, in three cisplatin-sensitive Chinese hamster ovary
(CHO)2 mutant cell lines. The mutant lines, CHO-MMC6, CHO-MMC1, CHO-MMS2,
displayed inherent sensitivity to cisplatin (2.2, 4.1 and 10.6-fold,
respectively) compared to the CHO-K1 line from which they were derived. CHO-MMS2
was the only mutant to show sensitivity to UV and this was slight (< 2-fold).
None of the mutants displayed increased sensitivity to X-irradiation. The CHO
MMS2 cell line appeared to have multiple mechanisms involved in its sensitivity
to cisplatin, including increased drug accumulation, decreased levels of
glutathione and a decreased capacity for DNA repair. The CHO-MMC1 mutant
demonstrated reduced ability for DNA repair in a host cell reactivation assay,
but no difference in drug accumulation or glutathione levels compared to the
parent. The CHO-MMC6 cell line was not defective in any of the mechanisms
studied. These three mutant cell lines demonstrate that similar mechanisms may
account for inherent sensitivity or resistance to cisplatin, and suggest that
multiple mechanisms may determine the sensitivity of human tumours to cisplatin.
PMID- 9653451
TI - Hydrogen peroxide induces protection against lethal effects of cumene
hydroperoxide in Escherichia coli cells: an Ahp dependent and OxyR independent
system?
AB - Pretreatment with 2.5 mM H2O2 protects bacterial cells against cumene
hydroperoxide killing. This response is independent of the OxyR system, but
possibly involves the participation of Ahp protein, since ahp mutants are not
protected. Treatment of bacterial cells with high H2O2 concentrations caused an
alteration on the electrophoretic profile of the smaller subunit (22-kDa) of Ahp.
This alteration does not require novel gene products and is not dependent on the
OxyR protein. In this way, we propose that the modification of the 22-kDa subunit
of Ahp by high H2O2 concentration may be responsible for the protection against
the lethal effects of cumene hydroperoxide.
PMID- 9653452
TI - Proficient deoxyribonucleic acid repair of methylation damage in hamster ERCC
gene mutants.
AB - Three major pathways, nucleotide excision repair (NER), base excision repair
(BER) and O6-methylguanine-DNA methyltransferase (MGMT), are responsible for the
removal of most adducts to DNA and thus for the survival of cells influenced by
deoxyribonucleic acid (DNA) adduct-forming chemicals. We have evaluated host cell
reactivation and cell survival of wild type Chinese hamster ovary cells and of
mutants in the NER-genes ERCC1, ERCC2, and ERCC4 after treatment with the
methylating compounds dimethylsulfate and methylnitrosourea. No effect of the
three genes could be demonstrated, i.e., survival and host cell reactivation
after methylation damage in the mutants and the wild type cells were similar.
Gene-specific repair experiments confirmed the proficient removal of methyl
lesions. We conclude that the three nucleotide excision repair genes are
immaterial to the repair of methylation damage. This suggests that NER does not
play a role in the removal of methylation in mammalian cells and that BER and
MGMT are responsible for the survival of such cells, when they are challenged
with methylation of DNA.
PMID- 9653453
TI - ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines.
AB - In mammalian nucleotide excision repair (NER), the ERCC1 protein is known to act
as a complex with ERCC4 (XPF) protein, which is necessary for stability of ERCC1,
and this complex introduces an incision on the 5' side of a damaged site in DNA.
ERCC1 also binds to XPA protein to make a large protein complex at the site of
DNA damage. Since no human disease associated with ERCC1 has been identified,
Chinese hamster ovary (CHO) cell lines defective in ERCC1 are a unique source for
characterization of ERCC1 deficiency in mammalian cells. We have isolated the
full length ERCC1 cDNA from a wild-type CHO cell line and analyzed mutations in
two CHO cell lines which fall into complementation group 1 of UV-sensitive rodent
cell lines. One cell line, 43-3B, has a missense mutation at the 98th residue
(V98E). The in vitro translated mutant protein of 43-3B is unable to bind to XPA
protein. Although the mutant protein is able to bind to XPF protein in vitro, the
mutant protein is highly unstable in vivo. These defects presumably cause the NER
deficiency of this cell line. Another mutant, UV-4, has an insertion mutation in
the middle of the coding sequence, resulting in a truncated protein due to a
nonsense codon arising from the frameshift. Thus, these two mutant cell lines are
deficient in the function of the ERCC1 gene for NER.
PMID- 9653454
TI - Isolation and characterization of iridoviruses from the giant toad Bufo marinus
in Venezuela.
AB - In this communication we describe for the first time the isolation of 7
iridoviruses from the toad Bufo marinus and an unknown species of frog
Leptodactylus in Venezuela, South America. The viruses are icosahedral with
electron-dense cores, each of which is surrounded by an inner membrane, capsid
and a cell-derived envelope. The virus(es) have an average vertex to vertex
diameter of 160 nm and replicate in the cytoplasm of a range of cell lines.
Within the cytoplasm of infected cells, rarefied areas could be observed;
structures lacked cellular organelles and contained complete, empty and
developing viruses. Results from antigen-capture enzyme-linked immunosorbent
assays (ELISA) with polyclonal antibody raised against epizootic haematopoietic
necrosis virus (EHNV) indicated cross-reactivity between these isolates, Bohle
iridovirus (BIV) and frog virus 3 (FV3). Comparison of polypeptide and genomic
profiles indicated that the Venezuelan viruses shared many polypeptides of
equivalent molecular weight with type species FV3. There were, however,
differences between the group of Venezuelan viruses and FV3 and BIV. The viruses
belongs to the family Iridoviridae and the genus Ranavirus.
PMID- 9653455
TI - Taura syndrome of penaeid shrimp: cloning of viral genome fragments and
development of specific gene probes.
AB - The ssRNA genome extracted from purified Taura Syndrome Virus (TSV) was
transcribed into double-stranded, blunt-ended cDNA and was used to construct cDNA
libraries either in pUC 18 or in pBluescript II KS-vectors. Twelve recombinant
plasmids chosen after screening of the libraries were subjected to restriction
enzyme digestions for determination of size inserts and restriction maps. Two of
them, pP15 and pQ1, were selected for probe construction. The inserts, 1500 and
1300 base pairs (bp) respectively, were DIG-11dUTP-labelled and the corresponding
probes were named P15 and Q1. On northern blots and dot blots, using different
denaturation methods, the 2 probes hybridized specifically with extracted RNA-TSV
genome, TSV and infected TS shrimp homogenates. No positive hybridization was
obtained with other shrimp viruses tested [Infectious Hypodermal and
Hematopoietic Necrosis Virus (IHHNV) and Hepatopancreatic Parvovirus (HPV)]. The
specificity of the 2 probes was confirmed by in situ hybridization on
histological sections of TS diseased shrimps.
PMID- 9653456
TI - Virulence and antigenic characteristics of a cultured Rickettsiales-like organism
isolated from farmed Atlantic salmon Salmo salar in eastern Canada.
AB - The present study describes culture, virulence and antigenic characteristics of a
Rickettsiales-like organism (RLO) associated with mortality in farmed Atlantic
salmon in eastern Canada. Clinical disease was reproduced in naive Atlantic
salmon parr by intraperitoneal i.p. inoculation with kidney homogenate from
naturally infected fish. Pure cultures of RLO were isolated into chinook salmon
embryo (CHSE) cells from kidney of experimentally infected fish. The RLO caused
cytopathic effect in cultured CHSE-214 typified by coalescing areas of swollen
cells that eventually detached from the substrate. Bacteria in infected culture
supernatants reacted with Piscirickettsia salmonis-specific polyclonal sera or
monoclonal antibody (MAb) in an indirect fluorescent antibody test. IP
inoculation with cultured RLO resulted in mortalities of 100, 62, 22.5 and 0% in
Atlantic salmon, coho salmon, rainbow trout and common carp, respectively.
Cultured RLO were sensitive to chloramphenicol, flumequine, oxytetracycline and
oxolinic acid and insensitive to gentamicin and amphotericin B. RLO antigens were
compared with those of 3 strains of P. salmonis from Chilean salmon by SDS-PAGE
and immunoblotting. A silver-staining band of about 12 kDa was detected in
proteinase K (PK) digests of all RLO strains, and a diffuse band of about 15 kDa
was observed in 2 Chilean strains only. No other silver-stained bands were
visible in PK digests of any strain examined. The polyclonal serum recognized 9
protein bands and multiple non-protein bands extending from less than 20 kDa to
greater than 95 kDa in all isolates. The MAb reacted with an epitope in PK
digests that occurred in all 4 strains on structures of widely ranging molecular
masses, resulting in a ladder pattern similar to that obtained with polyclonal
serum. Treatment of PK digests with periodic acid abolished reactivity with MAb
and polyclonal serum. Co-elution of 2-keto-3-deoxyoctonate and MAb reactivity
following size exclusion chromatography of solubilized P. salmonis suggested that
the MAb recognized a lipopolysaccharide-associated epitope in all 4 RLO isolates.
Cultural, virulence and antigenic similarities among the strains examined in the
present study indicate that the eastern Canadian salmonid RLO should be
considered a strain of P. salmonis.
PMID- 9653457
TI - Pathology of Piscinoodinium sp. (Protozoa: Dinoflagellida), parasites of the
ornamental freshwater catfishes Corydoras spp. and Brochis splendens (Pisces:
Callichthyidae).
AB - Piscinoodinium sp. (Protozoa, Dinoflagellida) was commonly found on routine
smears of samples of Brochis splendens and Corydoras spp. imported into Britain
from South America, and on samples of the same group of fish examined at the
exporters' holding facilities in Brazil. Infected fish had trophonts of different
sizes on the gills and skin. In histological sections of the skin, the trophonts
were found to be attached within depressions of different depths or enclosed by
hyperplastic epithelial cells. Such enclosed trophonts have not previously been
reported. Since some of the enclosed trophonts were dead, it was thought that
enclosure was a result of the deep penetration of the trophont and the host
defence mechanism. On the gills the Piscinoodinium infection was commonly
associated with epithelial hypertrophy, focal and diffuse hyperplasia, oedema of
the respiratory epithelium and lamellar fusion. The presence of this protozoan on
different species of fish from the same shipment suggests that the infection was
acquired before export. The source of infection and the stages of the export
process which expose the fish to the highest risk of infection are discussed.
PMID- 9653458
TI - Oral pharmacological treatments for parasitic diseases of rainbow trout
Oncorhynchus mykiss. I: Hexamita salmonis.
AB - Various drugs were evaluated as regards efficacy for the treatment of Hexamita
salmonis infection in rainbow trout. The results confirm the efficacy of
nitroimidazoles: infection was completely eradicated not only by metronidazole
(which has been recommended previously for the treatment of hexamitosis), but
also by benznidazole, ronidazole and secnidazole, which have not been assayed
previously. The non-nitroimidazoles albendazole, aminosidine, diethylcarbamazine
and nitroscanate also completely eliminated infection. The remaining non
nitroimidazoles tested (amprolium, bithionol, febantel, flubendazole, levamisole,
netobimin, niclosamide, nitroxynil, oxibendazole, parbendazole, piperazine,
praziquentel, tetramisole, thiophanate, toltrazuril, trichlorfon and
triclabendazole) were not effective.
PMID- 9653459
TI - In vitro cultivation and temperature-dependent growth of two strains of
Spironucleus barkhanus (Diplomonadida: Hexamitidae) from Atlantic salmon Salmo
salar and grayling Thymallus thymallus.
AB - Spironucleus barkhanus from muscle abscesses of farmed Atlantic salmon Salmo
salar L., and from the gall bladder of grayling Thymallus thymallus (L.) was
cultivated axenically in a medium routinely used for cultivation of the human
pathogen Giardia duodenalis. Trophozoites multiplied by binary division, but
multinucleated cells (< 10 nuclei) were frequently observed. Complete cell
divisions were never observed in these cells. Both strains grew at all
temperatures tested (5, 10, 15 and 20 degrees C). However, continuous growth of
the salmon strain at 20 degrees C was not possible. Growth potential, calculated
as minimum generation time, showed relatively small differences both between
strains and among temperatures, but the results indicate that the grayling strain
had both a slightly higher optimum temperature and a higher upper temperature
limit than the salmon strain.
PMID- 9653460
TI - Systemic spironucleosis in sea-farmed Atlantic salmon Salmo salar, caused by
Spironucleus barkhanus transmitted from feral Arctic char Salvelinus alpinus?
AB - A hexamitid flagellate was found in the gall bladder and intestine of Arctic char
Salvelinus alpinus in northern Norway. Scanning and transmission electron
microscopy showed this flagellate to be identical to Spironucleus barkhanus from
grayling Thymallus thymallus and farmed Atlantic salmon Salmo salar. It is
hypothesized that systemic spironucleosis in sea-caged Atlantic salmon was due to
transmission of flagellates from feral char to the salmon.
PMID- 9653461
TI - Generation and preliminary characterization of monoclonal antibodies directed to
glycerophospholipid:cholesterol acyltransferase (GCAT) native epitopes of
Aeromonas salmonicida.
AB - Four monoclonal antibodies (MAbs) directed to native
glycerophospholipid:cholesterol acyltransferase (GCAT) epitopes of Aeromonas
salmonicida were isolated using an esterase capture assay. The molecular mass of
this MAb-defined antigen was estimated to be 26 kDa in SDS-PAGE. Three different
epitope specificities of these MAbs were demonstrated. It was shown that all 4
MAbs recognize GCAT in culture filtrates of the strain MT004 excluding the
simultaneous trapping of other components. None of the MAbs react with the
denatured GCAT in Western blots.
PMID- 9653462
TI - Mammographic appearance of the breasts during pregnancy and lactation: false
assumptions.
AB - RATIONALE AND OBJECTIVES: It is believed that pregnant and lactating women have
dense breasts, thereby limiting the usefulness of mammography. To our knowledge,
no reports have been published on this topic for nearly 4 decades. The purpose of
our study was to determine whether this assumption is accurate given current
state-of-the-art mammography. MATERIALS AND METHODS: Mammograms of 18 women (six
pregnant, seven lactating, and five who recently discontinued lactation) were
examined and compared with their baseline (before pregnancy or lactation)
mammograms and with mammograms of 18 age-matched control subjects. Studies were
scored for breast density according to the Breast Imaging Reporting and Data
System and evaluated for change in density and size. RESULTS: Three of the six
pregnant women had unchanged breast density compared with baseline studies and
had scattered fibroglandular or heterogeneously dense tissue. Of the three
without baseline studies, one had extremely dense, one had heterogeneously dense,
and one had scattered fibroglandular tissue. All seven lactating women had either
heterogeneously dense or extremely dense tissue. The breast tissue in four was
unchanged in density and increased in two; no baseline study was available for
the remaining patient. Seven studies in five women who had discontinued lactation
1 week to 5 months prior to mammography showed no change in density compared with
baseline. CONCLUSION: Pregnant and lactating women do not always have dense
breasts, and mammography can be performed without substantial concern for the
limitations of breast density. Mammography can be as useful in these women as it
is in other women with breast signs and symptoms.
PMID- 9653463
TI - Predictive model for the diagnosis of intraabdominal abscess.
AB - RATIONALE AND OBJECTIVES: The authors investigated the use of an artificial
neural network (ANN) to aid in the diagnosis of intraabdominal abscess. MATERIALS
AND METHODS: An ANN was constructed based on data from 140 patients who underwent
abdominal and pelvic computed tomography (CT) between January and December 1995.
Input nodes included data from clinical history, physical examination, laboratory
investigation, and radiographic study. The ANN was trained and tested on data
from all 140 cases by using a round-robin method and was compared with linear
discriminate analysis. A receiver operating characteristic curve was generated to
evaluate both predictive models. RESULTS: CT examinations in 50 cases were
positive for abscess. This finding was confirmed by means of laboratory culture
of aspirations from CT-guided percutaneous drainage in 38 patients, ultrasound
guided percutaneous drainage in five patients, surgery in five patients, and
characteristic appearance on CT scans without aspiration in two patients. CT
scans in 90 cases were negative for abscess. The sensitivity and specificity of
the ANN in predicting the presence of intraabdominal abscess were 90% and 51%,
respectively. Receiver operating characteristic analysis showed no statistically
significant difference in performance between the two predictive models.
CONCLUSION: The ANN is a useful tool for determining whether an intraabdominal
abscess is present. It can be used to set priorities for CT examinations in order
to expedite treatment in patients believed to be more likely to have an abscess.
PMID- 9653464
TI - Hysterosalpingography with videofluoroscopy: effect on radiologic practice in an
academic medical center.
AB - RATIONALE AND OBJECTIVES: The authors attempted to determine whether videotaping
the fluoroscopic portion of hysterosalpingography would result in changed
diagnoses or an increase in diagnostic confidence. MATERIALS AND METHODS: Ninety
nine consecutive outpatients underwent routine hysterosalpingography. The
fluoroscopic portion of the examination was captured on videotape. Two
consecutive interpretations of each hysterosalpingogram were made by attending
radiologists. First, spot radiographs were interpreted alone. Second, these
images were viewed along with videofluoroscopy. Concordance of and confidence in
findings for the two interpretations were assessed with the two-tailed Fisher
exact test. RESULTS: Interpretations of spot radiographs alone and with
videofluoroscopy were in agreement in 92 of 99 uterine examinations and 164 of
198 tubal examinations. For uterine examinations classified as normal,
interpretations of spot radiographs and videofluoroscopy were in agreement in 56
of 57 cases; there was no change in confidence with review of videofluoroscopic
images. For uterine examinations interpreted as abnormal, agreement was noted in
36 of 42 cases (P = .04), and confidence increased with videofluoroscopy in 10 of
42 cases (P = .00001). With normal tubal findings, interpretations agreed in 94
of 118 cases, and confidence increased in 56 of 118 cases (P = .002). With
abnormal tubal findings, interpretations agreed in 70 of 80 cases, and confidence
increased in 20 of 80 cases (P = .002). When findings with and without
videofluoroscopy were discordant, confidence was always higher after review of
video-fluoroscopic images. CONCLUSION: Review of videofluoroscopic images
obtained during hysterosalpingography increases the accuracy and confidence of
diagnoses compared with review of spot radiographs alone.
PMID- 9653465
TI - Educational outreach to mammography facility staff to assist with compliance with
the Mammography Quality Standards Act in rural North Carolina.
AB - RATIONALE AND OBJECTIVES: The purpose of this project was to develop and evaluate
an educational program targeted at mammography facilities in rural areas of North
Carolina that were having difficulty complying with the 1992 Mammography Quality
Standards Act (MQSA). MATERIALS AND METHODS: Fourteen facilities deemed at risk
for closure under MQSA were identified by state inspection personnel. Problems at
the facilities were evaluated by a radiologist, a physicist-educator, and a
radiation physicist through a written survey, review of phantom and clinical
images, and a site visit. Individual advice and instruction were provided on-site
by the physicist-educator, with written materials provided in follow-up. A repeat
site visit was made 4-6 months after the initial visit. RESULTS: Of 51 problems
identified at the 12 institutions that completed the program, 35 (69%) were
corrected. All facilities that had failing phantom scores at the inspection prior
to the intervention had passing scores at the inspection after the intervention.
There was a statistically significant increase in the sum of the phantom scores
for the facilities offered this intervention compared with those not offered it
(P = .03). CONCLUSION: This educational program improved mammography quality at
participating facilities.
PMID- 9653466
TI - Pharmacokinetics of gadodiamide injection in patients with severe renal
insufficiency and patients undergoing hemodialysis or continuous ambulatory
peritoneal dialysis.
AB - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the
pharmacokinetics, dialysability, and safety of gadodiamide injection in patients
with severely reduced renal function not treated with renal replacement therapy
and patients undergoing hemodialysis or continuous ambulatory peritoneal
dialysis. MATERIALS AND METHODS: Twenty-seven patients--nine with severely
reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing
hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were
followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide
injection (0.1 mmol per kilogram body weight). RESULTS: Gadodiamide injection
caused no changes in renal function. In patients with severely reduced renal
function, the elimination half-life of gadodiamide injection was prolonged (34.3
hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An
average of 65% of the gadodiamide injected was eliminated during a hemodialysis
session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the
total amount of gadodiamide was excreted; this reflects the low peritoneal
clearance. In all patients, no metabolism or transmetallation of gadodiamide was
found. There were no contrast material-related adverse events. CONCLUSION:
Gadodiamide is dialysable and can safely be used in patients with severely
impaired renal function or those undergoing hemodialysis or continuous ambulatory
peritoneal dialysis. No precautions to increase the elimination are necessary.
PMID- 9653467
TI - Detection of pulmonary emboli at the segmental and subsegmental level with
electron-beam CT: validation in a porcine model.
AB - RATIONALE AND OBJECTIVES: The authors evaluated the sensitivity of electron-beam
computed tomography (CT) in the detection of segmental and subsegmental pulmonary
artery emboli in a porcine model. MATERIALS AND METHODS: Twenty-one segmental and
subsegmental branch pulmonary arteries in five swine were selectively
catheterized and embolized with gelatin sponge pledgets. The presence of emboli
was confirmed by means of contrast material-enhanced angiography. Contrast
enhanced CT scans of the pulmonary arteries were then obtained with 3-mm
collimation, 2-mm table travel between sections, and an imaging time of 100 msec
per section. Contrast material was injected at a rate of 2-3 mL/sec, depending on
the animal's weight, with a total dose of 60 mL for each scan. Cardiac-gated and
nongated scans were obtained, but breath holding was not possible in these
animals. RESULTS: Contrast-enhanced electron-beam CT scanning allowed correct
prospective identification of 18 of 21 emboli in the segmental and subsegmental
branches of the pulmonary arteries. The overall sensitivity was 86%. Cardiac
gating subjectively improved image quality but did not result in greater
sensitivity in the detection of emboli. The level of sensitivity was not affected
by the use of breath holding. CONCLUSION: Contrast-enhanced electron-beam CT is a
sensitive method for the detection of embolism in the segmental and subsegmental
pulmonary arteries.
PMID- 9653468
TI - Current status of musculoskeletal radiology fellowships in the United States.
PMID- 9653469
TI - Advanced breast biopsy instrumentation: a critique.
PMID- 9653470
TI - MINDscape and PubMed: Web sites that can change the way we work.
PMID- 9653471
TI - A protocol for management of a catastrophic complication of functional endoscopic
sinus surgery: internal carotid artery injury.
AB - Injury to the cavernous portion of the internal carotid artery is a well
recognized and dreaded complication of functional endoscopic sinus surgery.
Little information, however, has been presented in the Otolaryngology literature
regarding the etiology, prevention, or treatment of this complication. The
purpose of this study is to present a case report of a cavernous carotid artery
injury during functional endoscopic sinus surgery. Relevant anatomy, preventive
measures, and treatment approaches are discussed for this difficult problem.
PMID- 9653472
TI - Interobserver variations in assessment of antral disease from direct sinoscopic
observations compared to video recordings.
AB - We tested the reliability of visual clinical sinoscopic observations by using
video recordings. An edited video tape was made from the video-recorded bilateral
antral sinoscopies of nine patients included in a prospective case series of
inflammatory maxillary sinus disease in critically ill patients. An expert panel
of four consultant ENT surgeons made individual appraisals of the video using a
structured form. They had only been informed in general about the study, but had
no further case knowledge in order to avoid all biases. Concordance and
interobserver variabilities in the expert panel were compared in pairs. The
assessments of the expert panel were compared with the observations of the
performer, who was biased through individual case knowledge. Nine patients,
either nasotracheally intubated or tracheotomized, had ventilator treatment for
more than 7 days. One ENT surgeon performed all sinoscopies and made the direct
observations. Satisfactory agreement was found on mucosal alterations. The
concordance of recognizing bacterial infection was almost perfect. However, the
assessment of redness from a video recording displayed only chance agreement. The
differences between kappa statistic values within the expert panel group compared
to the comparisons of performer versus expert panel were not significant. The
case knowledge of the sinoscopist did not alter the assessments markedly and thus
seemed only to have minor influence. Video recording as a method for second
opinion was shown to be a useful technique, but will have to be further
developed.
PMID- 9653473
TI - Usefulness of patient symptoms and nasal endoscopy in the diagnosis of chronic
sinusitis.
AB - The diagnosis of chronic sinusitis can be difficult due to the variety and lack
of specificity of presenting symptoms. Sinus CT scanning is presently considered
the most sensitive and specific diagnostic method, but is expensive. In order to
determine whether a combination of patient symptoms and nasal endoscopy could be
used to predict which patients would have CT evidence of chronic sinusitis, we
conducted a prospective study in which 92 consecutive patients referred for
chronic sinusitis were required to fill out a questionnaire detailing their
symptoms. Their responses were then correlated with subsequent findings on nasal
endoscopy and CT scanning. Briefly, we found that patients with headache or
facial pain as their chief complaint were less likely to have evidence of
sinusitis than patients whose chief complaint was nasal obstruction or postnasal
drip. Also, nasal endoscopy was shown to be moderately sensitive and highly
specific in predicting results of CT scanning.
PMID- 9653474
TI - Intracranial complications of sinusitis: a pediatric series.
AB - Intracranial complications of sinusitis (ICS) (cerebral, epidural, and subdural
abscesses, meningitis, and dural sinus thrombophlebitis) remain a challenging and
contemporary topic. The progressive pneumatization and continued development of
the sinuses after birth and the late appearance of the frontal and sphenoid
sinuses imply that some infections would not appear until later childhood. We
reviewed the records at a large pediatric hospital between 1986 and 1995 and
found 10 children with 13 ICS (cerebral abscess, 5; extra-axial empyema, 5; and
meningitis, 3). Of 43 children with cerebral abscess and 16 with extra-axial
abscesses treated in this period, 12% of cerebral and 63% of extra axial
abscesses were due to a sinogenic source. Multiple intracranial and extracranial
complications of sinusitis in a single patient were common. The average age of
children with ICS was 12.2 years old. We present these 10 cases and discuss their
presentation, microbiology, and clinical course. Although the majority presented
with a classic picture of headache, altered mental status, and fever, a few had
symptoms that were more subtle. One child had recurrent meningitis, believed to
be due to skull base dehiscence after endoscopic sinus surgery (ESS). He has
required multiple otolaryngologic and neurosurgical procedures in an effort to
prevent further episodes of meningitis. Ultimately, nine of 10 patients survived
with an average hospital stay of 27.8 days (median of 17 days). The diagnosis of
ICS requires a high index of suspicion, imaging of the brain and paranasal
sinuses, and aggressive intervention.
PMID- 9653475
TI - Endoscopically guided frontal sinus beclomethasone instillation for refractory
frontal sinus/recess mucosal edema and polyposis.
AB - Despite its metabolic complications, systemic corticosteroid therapy remains a
mainstay in the treatment of refractory polyposis after endoscopic frontal
sinusotomy. Furthermore, topical nasal corticosteroids often fail, presumably due
to the relatively small dosage actually absorbed by the polyps. In order to
minimize steroid complications while increasing the locally absorbed dose,
beclomethasone (approximately 1 cc, 84 mcg/100 microliters) was instilled under
endoscopic guidance directly into the frontal sinus in 31 instances in 16
patients with postoperative frontal recess/sinus polyposis and mucosal edema. The
frontal recess/sinus polyposis/edema resolved completely in 9 frontal sinuses,
improved considerably in 7 frontal sinuses, improved minimally in 5 frontal
sinuses, and remained unchanged in 10 frontal sinuses. No complications were
noted. AM cortisol levels remained in the normal range. Endoscopically guided
frontal sinus beclomethasone instillation should be considered for the treatment
of refractory postoperative frontal sinus/recess polyposis/edema. Further basic
and clinical research into the pathophysiology of the nasal mucosa is also
warranted.
PMID- 9653476
TI - Efficacy of an aqueous and a powder formulation of nasal budesonide compared in
patients with nasal polyps.
AB - Nasal polyps are commonly treated surgically. Intranasal administration of
topical corticosteroids has gained increased acceptance as a treatment
alternative. The aim of our study was to compare the efficacy of treatment of two
formulations of budesonide with placebo on nasal polyps. At four Danish clinics
138 patients suffering from moderate or severe nasal polyps were randomized to a
twice daily treatment with Rhinocort Aqua 128 micrograms, Rhinocort Turbuhaler
140 micrograms or placebo (Astra Draco, Sweden) for 6 weeks. Polyp size (primary
efficacy variable), nasal symptoms, sense of smell, and patients' overall
evaluation of treatment of efficacy were assessed by scores. Polyp size was
reduced significantly in both budesonide treated groups compared with placebo,
but there was no statistical difference between the two actively treated groups.
Patients' nasal symptom scores was significantly more reduced in the Aqua
compared to the Turbuhaler treated group, and both reduced symptom scores were
significantly better compared to placebo. Sense of smell was significantly
improved in the actively treated groups compared to placebo. The proportion of
patients rating substantial or total control over symptoms after 6 weeks
treatment was 60.9% and 48.2% in the Aqua and Turbuhaler-treated groups,
respectively, which was significantly better compared with 29.8% in the placebo
treated group. Rhinocort Aqua and Rhinocort Turbuhaler were equally well
tolerated.
PMID- 9653477
TI - Frontoethmoidectomy with Sewall-Boyden reconstruction: alive and well, a 25-year
experience.
AB - Recent controversies in the rhinologic literature regarding surgical management
of the frontal sinus center around relatively new techniques using endoscopic
intranasal approaches. Few authors have addressed the concept of frontal "duct"
reconstitution, relying instead upon variations of the stenting concept, which
fail at least 30% of the time. Some oral presentations and discussions in the
past have gone so far as to say that external frontoethmoidectomy is an
antiquated operation with few indications. One reason for its recent disfavor
concerns the reported high rate of postoperative naso-frontal drainage track
stenosis leading to recurrent disease. The senior author has a 25-year experience
with a frontal recess reconstruction technique known as the Sewall-Boyden flap.
This technique, coupled with the frontoethmoidectomy approach, has been effective
with a low failure rate in 41 cases. This article serves to remind sinus surgeons
of a safe, effective technique for establishing a drainage track from the frontal
sinus: external fronto-ethmoidectomy with Sewall-Boyden flap reconstruction.
PMID- 9653478
TI - The evaluation of ciliary function: electron versus light microscopy.
AB - Diagnosing Primary Ciliary Dyskinesia can often be difficult. Physical findings
suggest the disease, but definitive diagnosis should be made with a ciliary
biopsy. Twenty biopsies were obtained from 16 patients and all underwent both
light and electron microscopic examination. In 8/20 (40%) there was a discrepancy
between the different imaging techniques. Therefore, light microscopy should be
used to assess adequacy of biopsy and motion of the cilia along with electron
microscopy to examine ultrastructure.
PMID- 9653479
TI - Muscarinic ciliostimulation requires endogenous prostaglandin production.
AB - Prostaglandin E2 (PGE2) is a known modulator in upper airway ciliary activity and
may be involved in the transduction of the muscarinic acetylcholine receptor
signal. We studied the in vitro effects of muscarinic ciliostimulation on ciliary
beat frequency (CBF) and PGE2 in human adenoid explants to determine whether PGE2
production is an essential step in the signal transduction mechanism.
Methacholine applied to adenoid explants significantly increased ciliary beat
frequency. This effect was blocked by the application of diclofenac, a
cyclooxygenase inhibitor. Using radioimmunoassay, PGE2 production was measured
during ciliostimulation with methacholine. Methacholine produced a significant
increase in production in PGE2 during ciliostimulation. The roles of
phospholipase C and phospholipase A2 in prostaglandin production were
investigated by inhibiting these enzymes. D609, a phospholipase C inhibitor,
significantly inhibited ciliary beat frequency increase and PGE2 production
during methacholine stimulation. However, PACOCF3, a phospholipase A2 inhibitor,
did not block ciliary beat frequency increase or PGE2 production in response to
methacholine. These data show that phospholipase C is required for PGE2
production and ciliostimulation.
PMID- 9653480
TI - Subjective comparison of Nd:YAG, diode, and CO2 lasers for endoscopically guided
inferior turbinate reduction surgery.
AB - Lasers using different wavelengths and delivery systems have been used to reduce
the inferior turbinate mass when hypertrophic inferior turbinates obstruct the
nasal airway. Different laser systems produce different laser-tissue
interactions. This study presents a comparison between three laser systems: CO2,
Nd:YAG, and Diode lasers for inferior turbinate reduction surgery, all performed
under endoscopic control. A total of 46 patients were randomized into three
treatment groups and followed for more than 1 year. Subjective and objective data
were collected. Subjective impressions of improved nasal airway was achieved in
41% (Diode), 47% (Nd:YAG) and 57% (CO2) and was not statistically significant.
There was more postoperative bleeding in the CO2 laser group, with 3 patients
requiring tamponade. The CO2 laser procedure also took longer to perform. These
results failed to show a significant difference between the different lasers for
inferior turbinate reduction. Overall, the results were not impressive.
PMID- 9653481
TI - Correction of the twisted nose deformity: a surgical algorithm using the external
rhinoplasty approach.
AB - Successful correction of the twisted nose is challenging due to the complex
nature of the underlying anatomic deformity. Although the literature has in
general supported endonasal rhinoplasty techniques for the twisted nose, we
propose a surgical algorithm using the external rhinoplasty approach. The
algorithm offer a stepwise, structured method that is adaptable to individual
variations in anatomic deformity. The advantages and relative disadvantages of
the external rhinoplasty approach are discussed, and a clinical experience of 30
patients is reviewed. Application of the external rhinoplasty algorithm in
correction of the twisted nose can yield consistently satisfactory functional and
aesthetic results.
PMID- 9653482
TI - The versatile autogenous rib graft in septorhinoplasty.
AB - In the graft depleted revision rhinoplasty patient and the patient with major
tissue needs, alternatives to septal and conchal cartilage grafts are needed. The
costal cartilage graft and rib bone/costal cartilage combination graft are
excellent alternatives. In this study 14 patients received 40 grafts from 20
autogenous ribs harvested during septorhinoplasty. Materials were harvested for
use as septal replacement grafts, cantilevered grafts, dorsal onlay grafts,
columellar struts, and tip grafts. Patient followup was 6 to 31 months, and no
evidence of graft resorption or warpage was evident during that period.
Complications of harvest were minimal, and harvest techniques are detailed.
PMID- 9653483
TI - Once more in St. Gallen.
PMID- 9653484
TI - HCV and lymphoproliferative diseases.
PMID- 9653485
TI - Enhancing the therapeutic index of concomitant chemoradiotherapy for head and
neck cancer.
PMID- 9653486
TI - Cost-effectiveness analysis in oncology.
AB - Physicians are faced with a burgeoning literature of economic studies. However,
most physicians have little training in evaluating economic research. Economic
studies involve a comparison of the costs and benefits of alternative treatment
options. To be of use for medical decision making, they should meet appropriate
methodological standards. These include clear specification of the research
question and the perspective from which the study is being undertaken, comparison
of relevant treatment options, identification and quantification of all important
costs and benefits, the use of discounting to allow for time preferences for
costs and benefits, and sensitivity analyses to test the robustness of the
study's results. Unfortunately, not all adhere to these principles. Physicians
need to be able to understand and critically assess the quality of economic
studies, and the applicability of the results to their own situation, in order to
participate in medical policy decisions.
PMID- 9653487
TI - Randomized controlled trials in cancer: improving the quality of their reports
will also facilitate better conduct.
AB - There has been a renewed interest in ways to help improve the quality of reports
of clinical trials recently. In this paper we describe these developments. This
work has also focused increased attention on how clinical trials are planned and
executed. Some common problems are reviewed and suggestions for improving their
conduct are also discussed.
PMID- 9653488
TI - Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all
CMFs alike? The International Breast Cancer Study Group (IBCSG).
AB - The first reported effective adjuvant combination regimen for patients with
operable breast cancer comprised oral cyclophosphamide (C) days 1-14 with
intravenous methotrexate (M) and fluorouracil (F) on days 1 and 8, repeated every
28 days ('classical' CMF). These drugs have since been extensively used with or
without endocrine therapies and/or other cytotoxics, as well as with radiation
therapy to the chest wall yielding conflicting results. Although doses and
schedules have varied widely, the combination of these three drugs has been
generically referred to as CMF. Evidence exists that reducing the dose and/or
altering the schedule of CMF ('modified' CMF) have compromised its efficacy in
metastatic breast cancer. Reduction below standard dose of a similar regimen also
gave inferior results in the adjuvant setting. In fact, the recently reported
improved outcome of adding radiation therapy to CMF was only demonstrated in
comparisons with a 'modified' CMF. Furthermore, trials in women with estrogen
receptor-positive breast cancer, which did not demonstrate any significant
benefit for the addition of adjuvant CMF to tamoxifen compared with tamoxifen
alone, also used 'modified' CMF. Therefore, adherence to the 'classical' dose and
schedule is recommended when CMF is used in adjuvant therapy.
PMID- 9653489
TI - Clinico-pathological characterization of hepatitis C virus-related B-cell non
Hodgkin's lymphomas without symptomatic cryoglobulinemia.
AB - BACKGROUND: Epidemiological evidence has suggested an association between
hepatitis C virus (HCV) infection and B-cell lymphoproliferation. We studied the
prevalence of HCV infection in a series of de novo B-cell non-Hodgkin's lymphoma
(B-NHL) cases and correlated virological findings with clinico-histological
features. PATIENTS AND METHODS: One hundred fifty-seven patients with de novo B
NHL were included in the study. Their serum was examined by ELISA and RIBA for
the presence of anti-HCV antibodies, and either the peripheral blood mononuclear
cells or the pathology tissues of all of the patients were examined by reverse
transcriptase polymerase chain reaction for the presence of HCV RNA sequences.
RESULTS: HCV infection occurred in 22.3% of B-NHL patients and was documented
before the diagnosis in about half of the positive cases. Of interest, HCV
infection was more frequently found in follicular center, marginal zone and
diffuse large-cell lymphoma types, but was not associated with symptomatic
cryoglobulinemia. The median survival time was 48 months in HCV-positive and 52
months in HCV-negative B-NHL patients. CONCLUSIONS: Our findings strengthen the
pathogenetic link between HCV and B-NHL and show that HCV infection may be
associated with the malignant proliferation of defined B-cell subsets other than
the immunoglobulin Mk B-cell subset involved in the pathogenesis of mixed
cryoglobulinemia type II and associated lymphoplasmacytoid lymphoma type. HCV
related liver disease did not affect the survival of our B-NHL patients.
PMID- 9653490
TI - Impact of hepatitis C virus infection on clinical features, quality of life and
survival of patients with lymphoplasmacytoid lymphoma/immunocytoma.
AB - BACKGROUND: The non-Hodgkin's lymphoma (NHL) subgroup most frequently associated
with hepatitis C virus (HCV) infection is the lymphoplasmacytoid
lymphoma/immunocytoma (Lp-Ic). We have assessed the impact of the infection on
the clinical features, quality of life and survival of HCV+ve Lp-Ic patients as
compared to its impact in HCV-ve patients. PATIENTS AND METHODS: Seventy patients
with Lp-Ic consecutively observed over a six-year period were studied. Clinical,
virological and histopathological features were recorded at diagnosis. Quality of
life was assessed using a scoring system including disease-related symptoms,
performance status, working ability, hospital admissions and therapies required.
RESULTS: Eighteen patients (26%) with HCV infection were identified. Significant
differences between those patients and the HCV-ve group included number of
symptomatic patients, Hb levels, serum protein levels, entity of the IgM
monoclonal component, number of patients with cryoglobulins and with organ
(liver, kidney) involvement, and entity and pattern of bone marrow infiltration.
Survival rates were similar (P = 0.8383), but the quality-of-life score was
significantly worse for the HCV+ve patients (P = 0.002). All anti-HCV Ab+ve
patients tested positive for HCV RNA; genotype 2ac was detected in a significant
proportion of cases. CONCLUSIONS: This study confirms that HCV infection is
present in about one-third of patients with Lp-Ic. HCV infection does not seem to
affect the overall survival of patients with Lp-Ic, but it affects the clinical
expression of the disease, so that the overall quality of life of HCV+ve patients
is significantly worse.
PMID- 9653491
TI - Selective cytoprotection with amifostine in concurrent radiochemotherapy for head
and neck cancer.
AB - BACKGROUND: Amifostine has reduced toxicities associated with radiation therapy
and platinum-based chemotherapy. In a phase II randomized trial, we investigated
the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy
(RCT) in patients with head and neck cancer. PATIENTS AND METHODS: Thirty-nine
patients with stage III or IV squamous cell carcinomas of the head and neck
received RCT (following surgery or as primary treatment). Radiotherapy was given
five days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy in
conjunction with carboplatin 70 mg/m2 on days 1 through 5 and days 21 through 26.
Eligible patients were randomised to receive RCT alone or preceded by a rapid
infusion of amifostine (500 mg) on the days when carboplatin was administered.
RESULTS: Patients receiving amifostine + RCT (n = 25) had significantly reduced
mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparison with patients
receiving RCT alone (n = 14). Additionally, patients receiving amifostine + RCT
had significantly less thrombocytopenia (P = 0.001) and leukopenia (P = 0.001).
At 12 months following therapy, 79% of patients receiving amifostine + RCT had no
evidence of disease compared with 64% of those receiving RCT alone. CONCLUSIONS:
Amifostine reduces the RCT-induced toxicities in patients with head and neck
cancer and has no negative impact on antitumour efficacy.
PMID- 9653492
TI - Alternating triple therapy for the treatment of intermediate grade and
immunoblastic lymphoma.
AB - BACKGROUND: CHOP is currently considered the gold standard of treatment for
intermediate grade lymphomas. We designed a new regimen known as 'ATT'
(alternating triple therapy) which uses three non-cross resistant combinations in
alternating sequence for nine cycles. MATERIALS AND METHODS: This is a phase II
clinical trial with comparison to CHOP/CMED historical controls using prognostic
factors. The tumor score system was used to evaluate the results of this trial.
Two hundred sixty-eight eligible patients who had one or more of the following
adverse features: bulky disease, elevated LDH or > 1 extranodal site were
analyzed. Outcome measures consist of survival and failure free survival.
RESULTS: At a median follow-up of 32 months, there was no statistically
significant difference in survival for those with favorable prognostic factors
(tumor score < or = 2). However, there was a statistically significant difference
in favor of ATT for those with unfavorable tumor scores. When we examined the
failure-free survival of those with unfavorable tumor scores, we again observed a
superiority for the ATT regimen over CHOP/CMED but the opposite was true for
those with favorable tumor scores. We also found a statistically significant
difference in favor of the ATT regimen when compared with CHOP/CMED for patients
< or = 60 years old with a tumor score > or = 3, while no advantage was found for
those > 60 years. CONCLUSIONS: ATT appears more effective but only for patients <
60 years old with unfavorable tumor scores. In those older than 60 years with
favorable tumor score, CHOP/CMED appears superior. ATT might be an adequate
regimen for young patients with poor prognostic features while CHOP/CMED might be
a better choice for those with good prognosis irrespective of age. For those > 60
years with unfavorable tumor scores neither ATT or CHOP/CMED were adequate
treatment. Because of the phase II nature of this study, these conclusions should
be considered as hypotheses which require prospective testing.
PMID- 9653493
TI - Application of interphase cytogenetics for the detection of t(11;14)(q13;q32) in
mantle cell lymphomas.
AB - BACKGROUND: The chromosomal translocation t(11;14)(q13;q32) is the hallmark of
mantle cell lymphoma (MCL) in which it can be detected cytogenetically in about
75% of cases. The t(11;14) translocation juxtaposes the bcl-1 locus in chromosome
band 11q13 next to the IgH locus in chromosome band 14q32 and, thus, leads to
deregulation of the cell cycle regulatory protein cyclin D1, which is encoded by
the CCND1 gene localized at the telomeric border of the bcl-1-locus. MCL has the
worst prognosis of all low-grade non-Hodgkin's lymphomas (NHL). In some
instances, however, histopathologic differentiation between MCL and other low
grade B-cell NHL is difficult. Therefore, detection of the t(11;14) translocation
is of essential diagnostic value for the risk-adjusted management of patients
with MCL. Unfortunately, chromosome analyses are frequently hampered by the low
yield and quality of tumor metaphases. As the 11q13 breakpoints are scattered
over a region of more than 120 kb the application of molecular genetic techniques
is also limited. PATIENTS AND METHODS: We established an interphase fluorescence
in situ hybridization (FISH) approach for the detection of the t(11;14)
translocation by use of a cosmid probe hybridizing to the IgH constant region and
a YAC spanning the bcl-1 region. Cells containing a t(11;14) translocation show a
colocalisation of the signals for IgH and bcl-1. Eight control samples and 15 MCL
specimens were investigated. RESULTS: According to our control studies, samples
containing more than 10% of cells with this signal constellation can be diagnosed
as carrying a clonal t(11;14) translocation. All eleven MCL found to carry the
t(11;14) translocation by chromosome analysis were positive in our FISH assay.
Additionally, two of four MCL lacking a clonal t(11;14) translocation by
chromosome analysis were shown to carry this aberration in 14% and 37% of
interphase nuclei. Southern blot data indicate that our FISH assay reliably
detects the t(11;14) translocation irrespective of the location of the
breakpoints within the bcl-1 region. CONCLUSIONS: The described interphase FISH
assay provides a reliable and routinely applicable tool for diagnosis of the
t(11;14) translocation.
PMID- 9653494
TI - Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody
(IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. The IDEC-C2B8 Study Group.
AB - BACKGROUND: In clinical trials in the USA, IDEC-C2B8 (a mouse-human chimeric anti
CD20 monoclonal antibody) has demonstrated high response rates with only mild
toxic effects in relapsed B-cell lymphoma at a dose of four weekly 375 mg/m2
infusions. The aim of the present trial was to determine whether or not this dose
is practically applicable to Japanese patients with relapsed B-cell lymphoma with
respect to safety, pharmacokinetics and efficacy. PATIENTS AND METHODS: Patients
with relapsed CD20+ B-cell lymphoma received intravenous infusions of IDEC-C2B8
once a week for four weeks. A total of 12 patients (four at 250 mg/m2 and eight
at 375 mg/m2) were enrolled. RESULTS: All 11 eligible patients treated with
either dose level tolerated IDEC-C2B8 well. Commonly observed adverse drug
reactions were grades 1 or 2 non-hematologic toxicities during the infusion,
consisting mostly of flu-like symptoms and skin reactions. All of the observed
hematologic toxicities were of grade 3 or less, and transient. A rapid and
sustained B-cell decrease in peripheral blood was observed, but no infectious
episodes were encountered. Human anti-mouse and anti-chimeric antibodies were not
detected. Of the 11 eligible patients (eight with follicular, two with diffuse
large-cell and one with mantle cell lymphoma), two showed a complete response and
five showed a partial response, and all of the seven responders had lymphoma with
follicular histology. A pharmacokinetic analysis showed that the elimination half
life (T1/2) of IDEC-C2B8 was 445 +/- 361 hours, and that the serum antibody
levels increased in parallel with the course of infusions, and in most patients
was still measurable at three months. CONCLUSIONS: The dose of four weekly 375
mg/m2 infusions of IDEC-C2B8 is safe and effective in Japanese patients with
relapsed B-cell lymphoma. Further studies evaluating IDEC-C2B8 are warranted.
PMID- 9653495
TI - The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced
colorectal carcinoma: results of a phase III trial. Swiss Group for Clinical
Cancer Research (SAKK).
AB - PURPOSE: A wide variety of fluorouracil (FU)-plus-leucovorin (LV) dose schedules
are in clinical use for the treatment of advanced colorectal cancer. Only the
monthly low-dose LV-plus-FU regimen, as used by the North Central Cancer
Treatment Group, has demonstrated a lasting survival benefit as opposed to FU
alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this
regimen for a confirmatory phase III trial but used the same dose-intensity of
fluorouracil in both treatment arms. PATIENTS AND METHODS: Patients with
inoperable or metastatic colorectal cancer were randomized to receive monthly FU
400 mg/m2/day plus LV 20 mg/m2/day as intravenous push daily for five days, or FU
alone. RESULTS: Three hundred nine of the 310 patients randomized were eligible
and included in the analysis. The objective response rate for patients with
measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The
median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the
overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors
for survival were performance status, weight loss, and disease symptoms. WHO > 2
toxicity, consisting of stomatitis (P = 0.001), diarrhea (P = 0.001), and nausea
(P = 0.001), was more pronounced for FU-plus-LV, without fatal events.
CONCLUSIONS: This is the largest published randomized trial to compare FU-plus-LV
to FU alone in advanced colorectal cancer. It confirms the survival benefit
obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU
plus-LV were acceptable to most patients, and they responded well to FU dose
reductions. In the absence of an ideal dose-intense FU monotherapy regimen,
monthly FU with low-dose LV provides a simple and economical means by which to
achieve adequate FU efficacy in the treatment of advanced colorectal cancer.
PMID- 9653496
TI - Improvement and plateau in survival of small-cell lung cancer since 1975: a
population-based study.
AB - BACKGROUND: Cytotoxic therapy appears to have improved short-term survival for
patients with small-cell lung cancer, but little is known about the results for
unselected patients and trends in long-term survival. PATIENTS AND METHODS: One
thousand seven hundred ninety-six patients with small-cell lung cancer diagnosed
between 1975 and 1994 in southeastern Netherlands. We studied treatment policy
for and survival of unselected patients since 1975, when cytotoxic therapy
emerged. RESULTS: The proportion patients receiving chemotherapy, with or without
irradiation, almost tripled from 30% to 82% for patients younger than 70 years of
age and from 15% to 56% for those over 70, whereas the proportion receiving only
radiotherapy decreased from 36% to 5% in both age groups. The short-term (< 2
year) survival rate improved markedly between 1975 and 1989, especially for
patients younger than 70 (median survival increased from five to 10 months). Two
year survival remained poor (8%). Two percent of all patients younger than 70
years at diagnosis survived for at least eight years, but these patients still
represent an excess five-year mortality of 39%. CONCLUSIONS: In southeastern
Netherlands short-term survival of patients with small-cell lung cancer improved
markedly up to the end of the 1980s, but a major impact on cure rates has not
been achieved.
PMID- 9653497
TI - Evaluation of the EORTC QLQ-C30 questionnaire: a comparison with SF-36 Health
Survey in a cohort of Italian long-survival cancer patients.
AB - BACKGROUND: Despite the large amount of data available about the EORTC QLQ-C30
questionnaire, there have been very few studies focussed on long-survival cancer
patients, and no data are available on its performance in the Italian setting.
PATIENTS AND METHODS: Within the framework of a project aimed at evaluating the
characteristics of available HR-QOL questionnaires in the Italian language, the
EORTC QLQ-C30 questionnaire together with the Short Form 36-item Health Survey
(SF-36) were mail-administered to a sample of patients previously recruited in
two large multicenter randomized clinical trials on early breast and colon
cancers. The properties of the questionnaire were evaluated using standard
psychometric techniques and correlation analyses with demographic and clinical
independent variables. RESULTS: In the sample of patients who sent back the
questionnaires under evaluation, the EORTC QLQ-C30 showed satisfactory
acceptability (response rate = 64% and very low prevalence of missing at item and
scale level), and the psychometric analyses confirmed the multi-dimensional
conceptualisation in terms of convergent and discriminant validity. Moreover,
EORTC QLQ-C30 scales showed substantial correlation with the homologous SF-36
scales. Few socio-demographic (age, gender, schooling) and clinical (type of
cancer disease) variables were associated with HR-QOL. Breast cancer patients
reported, on average, worse physical health-related scores, but after adjustment
for age and education, most of the differences disappeared. CONCLUSIONS: These
findings confirm the validity and robustness of the EORTC QLQ-C30 in this sample
of long-survival Italian cancer patients. Further ad hoc validation studies are
required to evaluate its significance in these particular patients.
PMID- 9653498
TI - Mandibular pain as the leading clinical symptom for metastatic disease: nine
cases and review of the literature.
AB - BACKGROUND: Metastases to the jaws are a rare phenomenon. Nevertheless, the
appearance of non-specific symptoms such as toothache can signal the onset of
neoplastic disease in some patients. PATIENTS: In this article, we present
details of a 74-year-old patient with a history of breast cancer to illustrate
this point. Retrospectively, covering a time span of one year, we could identify
nine patients (1.2%) with metastatic disease to the mandible out of a total of
763 patients referred to our Maxillofacial Surgery department with non-specific
jaw pain. RESULTS: Four patients were subsequently diagnosed as having breast
cancer, two had lung cancer, one prostate cancer, one renal cell carcinoma and
one adenocarcinoma of unknown primary site. Only three of these patients had
documented tumor spread to bones before the onset of jaw pain. In the other
patients, the dental symptoms were either the first sign of a generalized
neoplastic disease, or indicated relapse of disease after long term disease free
interval. However, further work up disclosed generalized tumor spread with
additional organ- or bone-lesions in all patients, and the median survival was
only six months (range 3.5(-)+22) from diagnosis. CONCLUSION: Pain of uncertain
origin in the jaws should alert clinicians to the potential of metastatic disease
in patients with a history of cancer and a bone scintigraphy should be done to
rule out metastatic involvement. Although metastatic lesions in this area usually
herald generalized neoplastic spread according to our experience, prompt
diagnosis nevertheless can lead to useful palliation and an enhanced quality of
life.
PMID- 9653499
TI - Ifosfamide given by continuous-intravenous infusion in association with
vinorelbine in patients with anthracycline-resistant metastatic breast cancer: a
phase I-II clinical trial.
AB - BACKGROUND: Vinorelbine (VNR) is highly active in metastatic breast cancer (MBC)
and has shown an overall response rate of 40%-50% as first-line treatment. In
vitro, a synergy has been observed between this drug and ifosfamide (IFX). In
addition, the pharmacokinetics of IFX suggest that it may have greater activity
when given by continuous-intravenous infusion (c.i.v.i.). The aim of this study
was, therefore, to assess the antitumor efficacy and toxicity of the combination
of bolus VNR and c.i.v.i. IFX as second-line therapy in anthracycline-resistant
breast cancer patients. PATIENTS AND METHODS: Forty-two patients with MBC who had
already received anthracycline-based chemotherapy were treated with a regimen
consisting of IFX, by c.i.v.i. for 72 hours and bolus VNR. The courses were
repeated every three weeks for a maximum of eight cycles. Four dose
intensification steps were planned: IFX, 1.5 g/m2 on days 1-3 + VNR, 30 mg/m2 on
day 1 (six patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on day 1 (six
patients); IFX, 1.8 mg/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (six
patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (24 patients).
Sodium-2-mercaptoethane sulfonate (mesna) was associated with IFX at an infusion
ratio of 1:1 and, once the infusion was completed, per os every four hours for
three times. RESULTS: All of the 42 patients entered were assessable for
toxicity, and 41 of them for response. Neutropenia was the most frequently
occurring toxicity, but only five patients at the highest dose level (11.9%)
presented grade 4, and none of those at the first three steps. Other significant
toxic effects were mild (only grade I-II). The median relative dose intensity was
95% at the highest dose level and all of the treatments were administered on an
out-patient basis. The overall response rate was 36.5% with a CR rate of 4.8%
(two of 41 patients, all at the highest dose level) and a PR rate of 31.7% (13 of
41 patients). The median response duration was 7.0 months (range 2-13 months).
CONCLUSIONS: The present phase I-II study shows that the IFX and VNR combination
is an active and well-tolerated treatment in MBC and provides an alternative to
taxanes for patients previously treated with anthracyclines.
PMID- 9653500
TI - Clinical phase I study with one-hour paclitaxel infusion.
AB - BACKGROUND: Paclitaxel (PAC) is one of the major anti-cancer drugs, effective in
different tumors. Studies with 24-hour infusion with 135 mg/m2 and a three-hour
infusion with 175 mg/m2 showed a significant schedule-dependent toxicity. We
evaluated a one-hour infusion schedule within a phase I study to determine the
dose limiting toxicity (DLT), the maximum tolerated dose (MTD), and the anti
cancer efficacy. PATIENTS AND METHODS: Patients with advanced malignant tumors
were treated within cohorts by one-hour infusional paclitaxel starting with 150
mg/m2 and stepwise escalation with 25 mg/m2 increments. Therapy was repeated in
three-week intervals. Cycles were repeated until progression. Toxicity was
closely monitored, anti-cancer efficacy was only evaluated in those patients who
received at minimum two treatment cycles. RESULTS: Thirty-four patients entered
the study (11 NSCLC, five SCLC, seven ovarian cancer, one cervix cancer, nine
MBC, one HN cancer). The MTD was PAC 250 mg/m2. The DLT was central and
peripheral neuropathy (WHO grade 3). Other significant toxicities were fatigue,
myalgia/arthralgia and paraesthesia. No significant myelotoxicity was observed.
Totally twentyone patients were evaluable for response. A partial response was
observed in five (24%) patients (two NSCLC, two ovarian cancer, one head and neck
cancer). Three (14%) patients had stable disease and in 13 (62%) patients
progressive disease was observed. CONCLUSIONS: Paclitaxel 225 mg/m2 on day 1
administered as one-hour infusion and repeated every three weeks can be given
safely, featured no relevant myelotoxicity, and is the recommended dose for phase
II studies.
PMID- 9653501
TI - Paclitaxel hypersensitivity reactions: a role for docetaxel substitution.
PMID- 9653502
TI - Pneumocystis carinii pneumonia in breast cancer.
PMID- 9653503
TI - Amerind taxonomy and testable hypotheses.
AB - The acceptance of a 30,000 yr B.P. age for Valsequillo sets new parameters for
hypotheses of Paleoindian entry into America. A review of Amerind taxonomy
defines the early groups as Otamid-Sundadonts. Isolation in America led to an
adaptive radiation that has implications for the origin and dispersal of
Pithecanthropus.
PMID- 9653504
TI - [Secular trend in body height since the Neolithic period].
AB - The body height of children and adults is estimated on the basis of skeleton
material from the middle Elbe-Saale region since the Neolithic period. The men's
body height was calculated according to Breitinger (1938), the women's body
height according to Bach (1965), and the children's body height according to
Telkka et al. (1962). These estimates are compared with the mean body height of
living persons from the adult population and of Jena schoolchildren,
respectively. These are the following essential results: 1. Since 7000 years ago
changes of body height can be observed. There was an increase of the mean body
height from the Neolithic period until the Bronce age. In the A.D. era no clear
changes of the average values can be found until about the 12th century, after
which there occurred decreases seen until the 19th century. 2. The greatest
secular trends in children and adults arise in our century. 3. The influence of
different environmental factors on the body height in past and present is
discussed and the sex-specific reactions to changes of these environmental
factors are described. 4. It is pointed out that social, and/or geographic
influences can cause changes of the body height calculated from skeleton
material.
PMID- 9653505
TI - [Tooth root length and tooth neck diameter as indicators in sex determination of
human teeth].
AB - The length of the dental root and the diameter of the tooth neck are odontometric
parameters which to date have rarely been used for the differentiation of the
sexes. Teeth of 166 individuals from the early medieval burial ground of
Eichstetten (south Germany) were available for examination. A correlation
analysis was performed to show the possible dimensional interrelation of teeth
which, however, applies only to the dental neck parameters. Using only diameters
of the tooth neck and length of dental roots, it was possible to perform a new
sex determination for 68 of the 166 individuals. It shows a good coincidence with
a traditional sex determination. A traditional sex determination, performed in
advance, as well as the archeological assignment of typical sex related grave
goods were used for verification. For future sex determination based on teeth,
examinations are recommended to be restricted to the six-year molar, the first
upper premolar and, in particular, the canine. Also the dental neck diameter
proved to be more useful than the crown diameter. Dental root lengths can be
neglected. By comparing the results with those of a second Alamannic burial
ground it could be established that discriminant analyses performed within the
same population are highly congruent.
PMID- 9653506
TI - Size correlation in Wormian bones.
AB - This study examines the correlation in size between some Wormian bones (lambda
bone and lambdoid ossicles) and between them and some cranial measurements
concerning the cephalic index and cranial capacity. The sizes of the lambda bone
and lambda ossicles are not correlated among themselves. The female ossicle sizes
are correlated with cranial length and width.
PMID- 9653507
TI - Smoking status and its effect on cardiorespiratory system, body dimension and
plucking performance of Oraon tea garden labourers.
AB - Oraon tea leaf pluckers were examined in terms of their cardiorespiratory
functions which include blood pressure measurements and a number of lung function
tests. Anthropometric measurements and information on smoking history were
obtained. It is known from earlier studies that the individuals studied belong to
more or less similar economic and nutritional background. The results suggest
that smoking has an effect on cardiorespiratory functions, and may have an
indirect effect an anthropometric traits, but no effect of smoking on work
performance could be established from the present study.
PMID- 9653508
TI - [Arm folding--an overview].
AB - The literature concerning arm folding is reveiwed. This analysis could be based
on 121 populations. In addition to this the paper discusses incidence, sex, age
differences and genetical problems including twinning. The incidence of left arm
folding ranges from 20% to 65% (mean value 54%). The review shows a predominance
of the left-type in Europe. Age and sex differences are only small. Between arm
folding and handedness no relationship could be found, and only a very weak one
between arm folding and hand clasping. 13 authors examined arm folding in
families, and 2 in twins. The family data suggest that arm folding may be under a
certain genetic control, yet it is clear that no simple genetic model concerning
the inheritance can be assumed. Monozygotic as well as dizygotic twins show a low
rate of concordance, and the frequencies of R-R, R-L and L-L pairs in monozygotic
and dizygotic twins show a binomial distribution.
PMID- 9653509
TI - Thermal and EMG biofeedback learning in nonhuman primates.
AB - Four monkeys were found able to learn to raise and lower hand temperature and to
reduce muscle tension to low levels using feedback from the target physiological
system. The establishment of this model of biofeedback learning in monkeys
enables work on mechanisms mediating the modes of biofeedback most used in
clinical practice. Results suggest that biofeedback learning does not need to be
mediated by the type of human-specific cognitive strategies employed by humans.
PMID- 9653510
TI - Emotionally triggered asthma: a review of research literature and some hypotheses
for self-regulation therapies.
AB - Asthma is a common disease whose morbidity and mortality are rapidly increasing.
Panic disorder is common in asthma. Panic, other negative emotions, and a passive
coping orientation may affect asthma by producing hyperventilation, increased
general autonomic lability, a specific pattern of autonomic arousal that may
cause bronchoconstriction, and/or detrimental effects on health care behaviors.
Generalized panic is a risk factor for increased asthma morbidity. A repressive
coping style also appears to be a risk factor for asthma morbidity because it is
accompanied by an impaired ability to perceive symptoms, a necessary prerequisite
for taking appropriate remediation. Several self-regulation strategies are
hypothesized to be useful adjuncts to asthma treatment. Preliminary research has
been done on relaxation therapy, EMG biofeedback, biofeedback for improved
sensitivity in perceiving respiratory sensations, and biofeedback training for
increasing respiratory sinus arrhythmia. It is hypothesized that finger
temperature biofeedback also may be a promising treatment method, and that
relaxation-oriented methods will have their greatest effect among asthmatics who
experience panic symptoms, while improved perceptual sensitivity will be helpful
both for patients who panic and those with repressive coping styles.
PMID- 9653511
TI - Disinhibition in the gamma motoneuron circuitry: a neglected mechanism for
understanding myofascial pain syndromes?
AB - Dysregulation in the gamma motoneuron circuitry is proposed as one mechanism to
explain the development of trigger point activity in myofascial pain syndrome.
Dysregulation in this context is defined operationally as significantly (and
functionally) different levels of electrical activity detected in the same muscle
on the left and right sides of the body that is persistently present with
movement of that muscle. Neurophysiological concepts as they pertain to muscles
and motor control principles are reviewed. Research is integrated that ties
together material from diverse fields of psychology and medicine. Dysregulation
in the gamma motoneuron circuitry may lead to disinhibition of muscle that causes
it to remain hyperactive after contraction, generate excessive electrical
activity during movement, and/or inappropriately coactivate with other muscles
during movement. Any or all of these phenomena may occur with dysregulation. Such
dysregulation may be corrected by learning. Immediate clinical implications are
discussed, including the addition of specifically targeted neuromuscular
retraining procedures via surface electromyography, as well as some conceptual
and research issues that require further clarification.
PMID- 9653512
TI - Potential contributions of neck muscle dysfunctions to initiation and maintenance
of carpal tunnel syndrome.
AB - A biomechanical perspective of the carpal tunnel (CT) is reviewed that lends
itself to an understanding of carpal tunnel syndrome (CTS) from a broader
pathophysiological perspective than focusing narrowly or solely on nerve
disturbance in the extremity. A wider integration of physiological systems in the
etiology and maintenance of CTS is proposed that links muscular dysfunction in
the neck and possibly elsewhere to dysfunction at the CT. A significant subset of
individuals who develop CTS have a primary contribution from muscular
dysfunctions rather distal to the CT itself. Neurophysiological dysregulation of
normal inhibitory feedback at the level of the motoneuron pool specifically
involving gamma motoneuron impulses may be a primary contributing mechanism.
Empirical demonstration of amelioration of CTS symptoms by means of surface
electromyography (sEMG) retraining of dysfunctional neck muscle patterns is
reviewed as support for the hypothesized link. The specific retraining techniques
are described. Future conceptual and research directions are noted.
PMID- 9653513
TI - Ouabain induces apoptosis on PHA-activated lymphocytes.
AB - Apoptotic cell death plays a critical role in immune system homeostasis, and c
myc protooncogene deregulated expression is a component of this programmed
genomic response. Pharmacological intervention and modulation of peripheral
lymphocytes apoptosis would have important implications. The present results
indicate that ouabain, a specific inhibitor of Na+K(+)-ATPase, promotes an
increased expression of c-myc mRNA, and induces apoptosis in PHA-stimulated
lymphocytes. Furthermore, this ouabain-induced apoptosis cannot be counteracted
by the addition of exogenous IL-2.
PMID- 9653514
TI - Folate transport by prawn hepatopancreas brush-border membrane vesicles.
AB - The transport system of folic acid (Pte-Glu) by brush-border membrane vesicles
(BBMV) isolated from prawn (Penaeus japonicus) hepatopancreas, was studied by
measuring the uptake of Pte-Glu. This uptake was found to have two components,
intravesicular transport and membrane binding. Membrane binding was not affected
by the presence of a transmembrane pH-gradient at a short incubation period.
However, a transmembrane pH-gradient increased membrane binding at 60 min. The
transport of Pte-Glu appeared to be carrier-mediated, was stimulated by an
inwardly proton gradient (pH 5.5 outside, 7.4 inside) and was unaffected by a
sodium-gradient. The relationship between pH gradient-driven Pte-Glu uptake and
medium Pte-Glu concentration followed saturating Michaelis-Menten kinetics. Eadie
Hofstee representation of the pH gradient-driven Pte-Glu uptake indicated a
single transport system with a Km of 0.37 microM and Vmax of 1.06 pmol/mg
protein/15 s. These findings indicate that BBMV isolated from prawn
hepatopancreas possesses a Pte-Glu transport system similar to that described in
mammalian intestine.
PMID- 9653515
TI - The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester potentiates
insulin secretion stimulated by glucose and L-arginine independently of its
action on ATP-sensitive K+ channels.
AB - The nature of the action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L
arginine methyl ester (L-NAME) on hormone release from isolated islets was
investigated. We found that glucose-induced insulin release was potentiated by L
NAME in the absence or presence of diazoxide, a potent K+ATP channel opener, as
well as in the presence of diazoxide plus a depolarizing concentration of K+. At
a low, physiological glucose concentration L-NAME did not influence insulin
secretion induced by K+ but inhibited glucagon secretion. L-arginine-induced
insulin release was potentiated by L-NAME. This potentiation was observed also in
the presence of K+ plus diazoxide. Further, glucagon release induced by L
arginine as well as by L-arginine plus K+ and diazoxide was suppressed by L-NAME.
The results strongly suggest that the L-NAME-induced potentiation of insulin
secretion in response to glucose or L-arginine as well as the inhibitory effects
on glucagon secretion are largely mediated by L-NAME directly suppressing islet
NOS activity. Hence NO apparently affects insulin and glucagon secretion
independently of membrane depolarization events.
PMID- 9653516
TI - Differential rhodopsin regeneration in photoreceptor membranes is correlated with
variations in membrane properties.
AB - Rhodopsin, the major transmembrane protein in both the plasma membrane and the
disk membranes of photoreceptor rod outer segments (ROS) forms the apo-protein
opsin upon the absorption of light. In vivo the regeneration of rhodopsin is
necessary for subsequent receptor activation and for adaptation, in vitro this
regeneration can be followed after the addition of 11-cis retinal. In this study
we investigated the ability of bleached rhodopsin to regenerate in the
compositionally different membrane environments found in photoreceptor rod cells.
When 11-cis retinal was added to bleached ROS plasma membrane preparations,
rhodopsin did not regenerate within the same time course or to the same extent as
bleached rhodopsin in disk membranes. Over 80% of the rhodopsin in newly formed
disks regenerated within 90 minutes while only 40% regenerated in older disks.
Since disk membrane cholesterol content increases as disks are displaced from the
base to the apical tip of the outer segment, we looked at the affect of membrane
cholesterol content on the regeneration process. Enrichment or depletion of disk
membrane cholesterol did not alter the % rhodopsin that regenerated. Bulk
membrane properties measured with a sterol analog, cholestatrienol and a fatty
acid analog, cis parinaric acid, showed a more ordered, less "fluid", lipid
environment within plasma membrane relative to the disks. Collectively these
results show that the same membrane receptor, rhodopsin, functions differently as
monitored by regeneration in the different lipid environments within
photoreceptor rod cells. These differences may be due to the bulk properties of
the various membranes.
PMID- 9653517
TI - Computational observation of an ion permeation through a channel protein.
AB - The ion permeation process, driven by a membrane potential through an outer
membrane protein, OmpF porin of Escherichia coli, was simulated by molecular
dynamics. A Na+ ion, initially placed in the solvent region at the outer side of
the porin channel, moved along the electric field passing through the porin
channel in a 1.3 nsec simulation; the permeation rate was consistent with the
experimentally estimated channel activity (10(8)-10(9)/sec). It this simulation,
it was indicated that the ion permeation through the porin channel proceeds by a
"push-out" mechanism, and that Asp113 is an important residue for the channel
activity.
PMID- 9653518
TI - Depression, cognition, and functional correlates of recovery outcome after
traumatic brain injury.
AB - The present study investigated the prevalence and magnitude of depressive
symptomatology in a sample of patients who had sustained traumatic brain injury
(TBI) six months earlier. Depression was examined as a function of recovery
outcome status, and its association with neuropsychological functioning, personal
competency, and employability was also explored. Subjects were 100 patients who
had previously sustained moderate-to-severe TBI who were enrolled as research
subjects in the UCLA Brain Injury Research Center, and 30 matched control
subjects who had sustained traumatic injuries other than to the head six months
prior to evaluation. The results showed a significant association between
depression and recovery status as measured by the Glasgow Outcome Scale (GOS). A
significant majority of depressed subjects were found in the poorer GOS outcome
groups (severe and moderate disability), compared to TBI subjects who had good
GOS outcomes, and control subjects. This association was also reflected in the
magnitude of the mean depression scores on two self-report measures of
depression. However, no association was found between depression status and
performance on the neuropsychological measures. Effects of depression were found
only on an examiner-rated Patient Competency scale, and a metacognition measure
based on self-report. These results are discussed in terms of brain injury
severity, recovery status, and metacognition issues in TBI and other disorders.
PMID- 9653519
TI - Neuropsychological, psychosocial and vocational correlates of the Glasgow Outcome
Scale at 6 months post-injury: a study of moderate to severe traumatic brain
injury patients.
AB - Traumatic brain injury (TBI) subjects at Glasgow Outcome Scale levels 3 (severe
disability), 4 (moderate disability), 5 (good recovery), and an other-injury
control group (OIC) were compared in terms of neuropsychological, psychosocial,
and vocational functioning 6 months after injury. Subjects were a sample of 100
patients with a moderate to severe traumatic brain injury (TBI) and a matched
sample of 30 other-injury control subjects (OIC) enrolled in the UCLA Brain
Injury Research Center study of TBI outcome. Overall, the results showed a
systematic decrease in mean neuropsychological test performance as a function of
increasing GOS severity, as well as an increased prevalence of symptoms of
depression and lower ratings on measures assessing employability and capacity for
self care. TBI patients in the 'severe' and 'moderate disability' groups were
distinctly inferior to the 'good recovery' and 'OIC' groups, who were quite
similar to each other in terms of cognitive, psychosocial, and vocational
outcomes. The results demonstrate overall support for the predictive and
concurrent validity of the GOS 6 months post injury. Despite these results, which
strengthen the utility and appeal of the GOS for multicentre studies, concerns
still remain regarding GOS category 4 (moderate disability), which was shown to
lack sufficient discriminability in this study.
PMID- 9653520
TI - The effects of normal ageing on neuropsychological functioning following
traumatic brain injury.
AB - Increasing age is associated with greater absolute neuropsychological impairment
(e.g. slower processing speed, diminished memory), although it is unclear if
older individuals with traumatic brain injury (TBI) show greater relative
impairment than younger individuals with TBI. The current study evaluated the
effects of normal ageing on TBI by using age-based normative data to calculate
indices of relative decline from pre-morbid levels (expressed as z-deficit
scores) for different age groups (20-39 years, 40-59 years, 60+ years). The
sample included 279 individuals with TBI between the ages of 20 and 65 who were
assessed in a department of rehabilitation neuropsychology laboratory over a 4
year period. Spearman correlations and ANOVAs did not show age-related
differences in relative memory, attention or speed of processing abilities,
although results did indicate that increasing age is associated with relatively
less impairment in intelligence. The results suggest that the greater
neuropsychological impairment noted in older individuals with TBI is most likely
related to normal ageing. The importance of considering both absolute and
relative degrees of impairment is discussed.
PMID- 9653521
TI - Functional assessment of mild traumatic brain injury using SPECT and
neuropsychological testing.
AB - The aim of this study was to ascertain whether SPECT and neuropsychological
testing provide converging evidence of normal and abnormal regional cerebral
function in patients with mild traumatic brain injury (mTBI). Four patients with
mTBI were evaluated with SPECT and selected neuropsychological tests with
putative localizing capabilities to specific cortical regions. The performance of
each patient on each test was graded as either normal or abnormal. Additionally,
SPECT images were graded for normal and/or abnormal patterns of regional cerebral
blood flow (rCBF) in eight regions of the cortex. These data were then used to
predict outcomes from one modality to the other, i.e. rCBF patterns on SPECT were
used to predict either normal or abnormal performance on specific tests and
performance on specific tests was used to predict the presence or absence of rCBF
abnormalities on SPECT. Statistical analysis of composite data from all four
patients showed that test performance predicted SPECT findings, but SPECT
findings did not predict test performance.
PMID- 9653522
TI - The pathogenesis and clinical significance of traumatic subdural hygroma.
AB - Subdural hygroma (SDG) is a common post-traumatic lesion. Despite its common
occurrence, the pathogenesis and clinical significance are uncertain. The author
reviewed the literature to clarify the present knowledge on the pathogenic,
diagnostic and therapeutic aspects of this controversial lesion. A trivial trauma
can cause a separation of the dura-arachnoid interface, which is the basic
requirement for the development of a SDG. If the brain shrinks due to brain
atrophy, excessive dehydration or decreased intracranial pressure, fluid
collection may develop by a passive effusion. Most SDGs resolve when the brain is
well expanded. However, a few SDGs become chronic subdural haematomas, when the
necessary conditions persist over several weeks. Since the majority of patients
with a SDG do not show a mass effect, surgery is rarely required. Outcome is
closely related to the primary head injury not to the SDG itself. The complexity
of SDG depends on various factors including the dynamics of absorption and
expansion, duration of observation, and indication and rate of surgery, besides
variety of the primary head injury in types and severity. SDG is a common
epiphenomenon of head injury.
PMID- 9653523
TI - Transient global amnesia triggered by mild head injury.
AB - An episode of transient global memory loss was observed in a 27-year-old woman
following a mild head injury in a car accident. Her clinical and
neuropsychological profiles were indistinguishable from those of transient global
amnesia (TGA). This paper argues that a cause-effect relationship may be
postulated between head trauma and transient memory loss, perhaps as the result
of a very stressful situation such as a car crash.
PMID- 9653524
TI - Obsessional disorders during recovery from severe head injury: report of four
cases.
AB - Four cases of transient obsessional disorders following severe head injury are
described within the context of recovery from acute traumatic brain injury (TBI).
Obsessional features following TBI have important treatment implications in brain
injury rehabilitation settings, since emergence of this disorder in the acutely
brain injured patient poses a significant obstacle to interdisciplinary
rehabilitation. Although the numbers of patients described here and in previous
reports are too small to draw conclusions about the incidence of obsessional
disorders following TBI, these cases illustrate the importance of correctly
identifying and treating obsessional symptoms in the brain injured patient.
PMID- 9653525
TI - Amantadine: a potential treatment for the minimally conscious state.
AB - Pharmacologic strategies have been advocated to enhance the neurorehabilitation
of persons with severe traumatic brain injury. Dopaminergic pathways have been
felt to play a significant role in arousal. Employing single case design
methodology we present the case of a survivor of severe traumatic brain injury
who appeared to have a dose dependent response to the pro-dopaminergic medication
amantadine. Further research is necessary to clarify the role of pharmacotherapy
in the improvement of functional outcome.
PMID- 9653526
TI - Pharmacologic management of movement disorder after midbrain haemorrhage.
AB - Movement disorders following midbrain haemorrhage are infrequently encountered in
rehabilitation, and are uncommonly corrected by pharmacologic means. This report
describes a 20 year-old male with a prior history of cocaine abuse who presented
with a 4 day history of dysarthria and blurred vision following methamphetamine
abuse. Physical examination demonstrated hypertension, left facial hemispasm,
bilateral upward gaze paresis and ataxic gait. Magnetic resonance
imaging/magnetic resonance angiography (MRI/MRA) showed multifocal parenchymal
haematomas in the mesencephalic tegmentum, subcortical left front region and
right anterior thalamus consistent with cavernous angiomas. The patient was
transferred to rehabilitation on hospital day 5. The following day, he developed
choreoathetoid movements, dystonia, and aphasia, secondary to an extension of the
midbrain haemorrhage. Cogentin was initiated with slight improvement in
choreoathetoid movements. The patient began intensive multidisciplinary
rehabilitation therapy but after 18 days of therapy, the patient remained totally
dependent in activities of daily living (ADLs), transfers, mobility and was
unable to communicate in any manner. A trial of Sinemet was initiated, with
resultant steady improvement in functional ability over the next month. By
discharge, the patient was independent in ADLs and ambulation. By 9 months post
discharge follow-up, the patient was fully independent with normal cognition, and
had self tapered all medications without ill effect. Dopamine agonist trials of
appropriate duration appear indicated in cases of movement disorder (paucity or
excess) following midbrain lesions.
PMID- 9653527
TI - Forensic psychiatry.
PMID- 9653528
TI - Sexual recidivism in sex offenders.
AB - OBJECTIVE: To examine the recidivism rates of the various types of adult sex
offenders including incest offenders, extrafamilial child molesters,
exhibitionists, and rapists. METHOD: An examination of the literature over the
past 4 decades and the data from our own study group. RESULTS: Methodological
shortfalls and differences across the studies make statistical appraisal of the
results difficult. Nevertheless, there is a consensus that incest offenders are
less likely to reoffend compared with extrafamilial child molesters. Rapists and
exhibitionists are thought to be at a higher risk for recidivism. CONCLUSION: A
combined actuarial predictive approach in conjunction with empirically guided
clinical assessment is probably the best method to predict recidivism of sex
offenders.
PMID- 9653529
TI - The use of clozapine in the treatment of aggressive schizophrenia.
AB - The atypical antipsychotic drug clozapine was introduced to clinical practice in
1972. It is a dibenzodiazepine derivative with, among other known receptor site
activities, a relatively high D1/D2 receptor affinity ratio. The serious side
effects of bone marrow suppression and agranulocytosis delayed the acceptance of
clozapine into common clinical practice but scrupulous application of a
monitoring protocol led to adequate protection from these side effects. There is
now a broad consensus about the benefits of clozapine which supports the use of
clozapine as a first-line treatment of schizophrenia. There is good evidence that
relapse and rehospitalization drop to 22% of the incidence in preclozapine
treatment patients. The majority of responders are identified within 4 months of
treatment. Clozapine has been demonstrated to be an effective treatment for
neuroleptic refractory patients. Forty percent of clozapine-treated patients show
significant improvement, with 11% of treated patients showing no residual
psychosis. This review also describes the results of clozapine on aggressive and
violent assault in a patient population characterized by severe functional
deficits, typically chronic schizophrenia with severe impairment, chronic brain
syndromes, and developmental handicap. Prior to the introduction of clozapine
therapy, in a chronically disrupted milieu that precluded adequate psychosocial
programming, seriously assaultive behaviour resulting in peer and staff injury
was a common occurrence. Evidence suggests that clozapine is an effective medical
treatment for the target symptoms of hostile agitation, threatening, and
assaultive violence.
PMID- 9653530
TI - Stalking. Part I: An overview of the problem.
AB - OBJECTIVE: This paper is the first of a 2-part review on the topic of stalking.
It outlines the behaviours involved, epidemiology, motivation of offenders, and
mental health consequences for the victim. METHOD: Computerized literature
searches were used to identify relevant papers from psychiatric and legal
journals. Publications by victims' and women's organizations provided additional
information. RESULTS: Up to 1 in 20 women will be stalked during her lifetime.
The majority of victims are female, while the offenders are usually male.
Stalking behaviours range from surveillance to threatening aggressive or violent
acts. The majority of stalking relates to failed intimate relationships. Stalkers
may also suffer from erotomania or obsessional love with a primary psychiatric
diagnosis. Victims may experience anxiety, depression, guilt, helplessness, and
symptoms of posttraumatic stress disorder (PTSD). CONCLUSION: Stalking is a
serious offence perpetrated by disturbed offenders. It can cause major mental
health consequences, which are often poorly understood by society.
PMID- 9653531
TI - Stalking. Part II: Victims' problems with the legal system and therapeutic
considerations.
AB - OBJECTIVE: This paper is the second of 2 parts reviewing the topic of stalking.
It focuses on victims difficulties with the legal system and the
psychotherapeutic tasks for victims and therapists. METHOD: Computerized
literature searches were used to identify relevant papers from psychiatric and
legal journals. Publications by victims' and women's organizations provided
additional information. RESULTS: Victims suffer emotional consequences from being
stalked. Additional stress is caused by the legal system's lack of understanding
of the causes and consequences of stalking and inadequate and unenforced laws.
The treatment of victims requires a comprehensive approach, including education,
supportive psychotherapy, and discussion of practical measures. Therapists may
overidentify with the patient's powerlessness or hesitate to take on a case out
of fear of the stalker. Female therapists may protect themselves against the
realization of their own vulnerability by blaming the victim, while male
therapists may feel defensive or overprotective. CONCLUSION: Stalking is a crime
with major mental health consequences which is often poorly understood by
society. Therapists need to be aware of the victim's emotional reactions, the
types of legal and practical supports available, and the possible biases of
society. Further education and research should be encouraged.
PMID- 9653532
TI - [Instruments to evaluate fitness to stand trial:a review of recent literature].
AB - OBJECTIVES: To present current methods used to assess fitness to stand trial
(FST), draw a parallel between these methods and studies of factors associated
with decisions regarding FST, and describe the limits inherent to the field of
FST. METHOD: Survey of the relevant literature from Psychinfo and Medline
databases from 1967 to 1996 inclusively. RESULTS: Ten instruments were identified
for the systematic collection of information from persons assessed for FST. The
description and analysis of their psychometric qualities, however, indicate that
these instruments present some problems. CONCLUSION: Although some research has
shown that diagnosis is the factor most associated with decisions regarding FST,
no instrument includes a systematic assessment of psychopathology. If we take
into account the possible consequences of these decisions for the accused as well
as for society, these assessments and the recommendations that follow prove to be
extremely important.
PMID- 9653533
TI - Fitness, responsibility, and judicially ordered assessments.
AB - OBJECTIVE: To compare the characteristics of individuals assessed for fitness to
stand trial (FST) with those assessed for criminal responsibility (CR). METHOD:
This study examines all the consecutive requests of FST or CR addressed to the
only forensic psychiatric hospital in the province of Quebec and 2 prisons in the
Montreal area over a 1-year period. RESULTS: In all, 170 FST, 52 CR, and 29 both
FST and CR assessment requests were received (251 subjects). Psychiatrists'
recommendations and court verdicts of unfitness to stand trial or not criminally
responsible on account of mental disorders were mostly related to the presence of
a psychotic-spectrum disorder. There is generally a good agreement between
psychiatric recommendations and verdicts of the court, with the exception of
unfitness recommendations. CONCLUSIONS: Defendants referred for a FST or a CR
assessment displayed similar characteristics. However, although subjects with
psychotic disorders represented more than one-half of the unfit or not criminally
responsible verdicts, most of the subjects with psychoses were found competent to
stand trial or responsible.
PMID- 9653534
TI - Factors in delays in discharge from acute-care psychiatry.
AB - OBJECTIVE: To determine if there are any potential opportunities for patients to
be discharged earlier and to determine what factors are responsible for delays in
discharge. METHOD: A survey was completed by clinical staff of all patients on
the wards of 12 adult psychiatry units in the Greater Vancouver Regional Hospital
District (GVRD) for a 1-day period. The survey included a modified Brief
Psychiatric Rating Scale (BPRS) and the Discharge Readiness Inventory (DRI). A 1
month follow-up measured discharge and nondischarge outcomes. RESULTS: Of the 327
patients surveyed, 42% were ready for discharge at the time of the assessment,
and 37% of those who were ready were not discharged within 2 weeks. Delayed
patients had significantly higher scores for disorientation, hallucinations,
conceptual disorganization, and manifest psychopathology and significantly lower
scores for Community Adjustment Potential (CAP) (P < 0.05). The most frequent
reasons given for delays were ongoing medication adjustment, behaviour
stabilization, and discharge planning. Patients who were delayed were more likely
to need services, to need or be waitlisted for a residential placement, to be a
client of the community-based mental health team that provides ongoing support to
clients living in the community, to have a diagnosis of schizophrenia, and to
have had no previous psychiatric hospital admission. CONCLUSION: The removal of
all barriers to delays would reduce lengths of stay by 11% for this sample of
patients. This would require a shift of about 42 out of 327 beds to an alternate
level of care. These "earlier discharge patients" will need ongoing medication
and behaviour monitoring through a variety of community services.
PMID- 9653535
TI - Alcohol consumption and major depression in the Canadian population.
AB - OBJECTIVE: Various clinical studies have documented associations between alcohol
consumption and depressive disorders. In some circumstances, alcohol ingestion
may cause or worsen depression, whereas in other circumstances the direction of
causal effect may be reversed. The objective of this study was to evaluate
associations between alcohol consumption and major depression in the Canadian
population. METHOD: Data from the Canadian National Population Health Survey
(NPHS) were analyzed. This survey, conducted by Statistics Canada in 1994, used a
probability sample of 17,626 subjects. The NPHS included measures of alcohol
ingestion and a diagnostic screen for major depression (Composite International
Diagnostic Interview [CIDI] Short Form). RESULTS: Subjects reporting any drinking
in the year preceding the interview were more likely to have experienced an
episode of major depression during that time than subjects reporting no drinking.
Subjects reporting maximal ingestions of 5 or more drinks (and especially 10 or
more drinks) on at least 1 occasion during the preceding year were also at
greater risk of major depression than nondrinking subjects or subjects reporting
smaller maximal ingestions. Neither the average amount consumed daily nor the
frequency of drinking was associated with major depression. CONCLUSIONS: In the
general population, there is no simple relationship between the quantity or
frequency of alcohol consumption and the prevalence of major depression. Any
drinking and maximal consumption on 1 occasion, however, are related to the
prevalence of major depression. Further research is needed to delineate causal
mechanisms so that clinical and public-health interventions can be formulated.
PMID- 9653536
TI - Binge/purge symptoms and comorbidity in adolescents with eating disorders.
AB - OBJECTIVE: To identify the diagnostic subtypes of eating disorders (EDs), the
psychiatric comorbid diagnoses, and associated specific and nonspecific
psychopathology in a series of 120 adolescents undergoing standardized assessment
for an ED. METHOD: Consecutive patients referred to our large pediatric hospital
for ED assessment completed a semistructured diagnostic interview for children
and adolescents. The following self-report scales were administered to assess
specific and nonspecific psychopathology: the Children's Depression Inventory
(CDI), the Brief Symptom Inventory (BSI), the Eating Disorder Inventory 2 (EDI
2), and the Family Assessment Measure (FAM-III) of family functioning. RESULTS:
Female subjects with a mean age of 14.5 years and a mean body mass index (BMI) of
18.1 comprised 93% of the sample. The restrictive subtypes of anorexia nervosa
(AN) (43%) and eating disorder not otherwise specified (EDNOS) (16%) were the
most common diagnoses. Patients with restricting symptoms (R) could be grouped
together because they were more similar to each other with respect to self-report
symptoms of psychopathology than they were to patients with binge/purge (B/P)
symptoms and vice versa. Patients with R endorsed significantly fewer subjective
symptoms, both ED-specific and nonspecific, and rated their families functioning
better than did B/P patients. Comorbid, current major depressive disorders and
dysthymic disorders occurred in 66% of subjects, but depressive, dysthymic, and
oppositional disorders occurred in 96% of those with B/P symptoms. Severity of
the CDI was the best single discriminator between R and B/P subjects.
CONCLUSIONS: Adolescents with EDs in the early stage of their illness are similar
to adults with EDs in the following ways: they meet the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) criteria for subtypes of EDs
(excluding amenorrhea) and commonly have comorbid psychiatric disorders,
especially depressive disorders. Patients with B/P symptoms can be distinguished
from restricting subjects because they endorse significantly more ED-specific and
nonspecific psychopathology and have a higher frequency of comorbid Axis I
diagnoses (especially depressive disorders) than restricting patients.
Oppositional defiant disorder (ODD) occurs more commonly in adolescents with EDs
associated with B/P symptoms.
PMID- 9653537
TI - A community-based clinic survey of antidepressant use in persons with
schizophrenia.
AB - OBJECTIVE: To determine the rates of antidepressant and antipsychotic use in the
treatment of schizophrenia. METHOD: The primary therapists at 8 community mental
health centres in a metropolitan Canadian city completed a survey questionnaire
for all of their active clients. Information was collected about diagnoses,
medication treatments, and clinical variables. RESULTS: There were 3555 clients,
1552 (43.7%) of which had a diagnosis of schizophrenia. Of clients with
schizophrenia, 94% were prescribed antipsychotic medications, and 11.6% of these
were also prescribed antidepressant medications. There were differences between
the combination-treatment group and the antipsychotic-alone group in gender
ratio, rates of concurrent diagnoses of mood disorder, level of current
functioning, and total number of hospitalizations. CONCLUSION: In this community
based sample of clients with schizophrenia, antidepressants and antipsychotics
are commonly prescribed in combination, even though the rate of concurrent mood
disorders diagnoses is low. Further studies should clarify the efficacy and
indications for antidepressant use in this population.
PMID- 9653538
TI - Re: Boundary violations and personality traits among psychiatrists.
PMID- 9653539
TI - Re: Severe anticholinergic side effects with venlafaxine-fluoxetine combination.
PMID- 9653540
TI - Selective serotonin reuptake inhibitor discontinuation syndrome: putative
mechanisms and prevention strategies.
PMID- 9653541
TI - Re: A cross-sectional study of private psychiatric practices under a single-payer
health care system.
PMID- 9653542
TI - Mirtazapine withdrawal symptoms.
PMID- 9653543
TI - Family history of DSM-III-R schizophreniform disorder with good prognostic
features.
PMID- 9653544
TI - Bioinorganic chemistry and drug design: here comes zinc again.
AB - The structures and reactions of metal ions in proteins are of tremendous interest
in bioinorganic chemistry, as is the potential for metals in creating novel
medicines. New results combine these aspects in describing an unexpected mode for
metal-mediated drug efficacy that relies on well-established principles of
metalloprotein structure.
PMID- 9653545
TI - Small-molecule-based strategies for controlling gene expression.
AB - A central goal in chemical biology is to gain control over biological pathways
using small molecules, and the mRNA-synthesizing machinery is a particular
important target. New advances in our understanding of transcriptional regulation
suggests strategies to manipulate these pathways using small molecules.
PMID- 9653546
TI - High-throughput worms. NemaPharm, Inc.
PMID- 9653547
TI - Protein structures.
PMID- 9653548
TI - A high-affinity subtype-selective agonist ligand for the thyroid hormone
receptor.
AB - BACKGROUND: Thyroid hormones regulate many different physiological processes in
different tissues in vertebrates. Most of the actions of thyroid hormones are
mediated by the thyroid hormone receptor (TR), which is a member of the nuclear
receptor superfamily of ligand-activated transcription regulators. There are two
different genes that encode two different TRs, TR alpha and TR beta, and these
two TRs are often co-expressed at different levels in different tissues. Most
thyroid hormones do not discriminate between the two TRs and bind both with
similar affinities. RESULTS: We have designed and synthesized a thyroid hormone
analog that has high affinity for the TRs and is selective in both binding and
activation functions for TR beta over TR alpha. The compound, GC-1, was initially
designed to solve synthetic problems that limit thyroid hormone analog
preparation, and contains several structural changes with respect to the natural
hormone 3,5,3'-triiodo-L-thyronine (T3). These changes include replacement of the
three iodines with methyl and isopropyl groups, replacement of the biaryl ether
linkage with a methylene linkage, and replacement of the amino-acid sidechain
with an oxyacetic-acid sidechain. CONCLUSIONS: The results of this study show
that GC-1 is a member of a new class of thyromimetic compounds that are more
synthetically accessible than traditional thyromimetics and have potentially
useful receptor binding and activation properties. The TR beta selectivity of GC
1 is particularly interesting and suggests that GC-1 might be a useful in vivo
probe for studying the physiological roles of the different thyroid hormone
receptor isoforms.
PMID- 9653549
TI - Substrate binding and sequence preference of the proteasome revealed by active
site-directed affinity probes.
AB - BACKGROUND: The proteasome is a multicatalytic protease complex responsible for
most cytosolic protein breakdown. The complex has several distinct proteolytic
activities that are defined by the preference of each for the carboxyterminal
(P1) amino acid residue. Although mutational studies in yeast have begun to
define substrate specificities of individual catalytically active beta subunits,
little is known about the principles that govern substrate hydrolysis by the
proteasome. RESULTS: A series of tripeptide and tetrapeptide vinyl sulfones were
used to study substrate binding and specificity of the proteasome. Removal of the
aromatic amino-terminal cap of the potent tripeptide vinyl sulfone proteasome
inhibitor 4-hydroxy-3-iodo-2-nitrophenyl-leucinyl-leucinyl-leucine vinyl sulfone
resulted in the complete loss of binding and inhibition. Addition of a fourth
amino acid (P4) to the tri-leucine core sequence fully restored inhibitory
potency. 125I-labeled peptide vinyl sulfones were also used to examine inhibitor
binding and to determine the correlation of subunit modification with inhibition
of peptidase activity. Changing the amino acid in the P4 position resulted in
dramatically different profiles of beta-subunit modification. CONCLUSIONS: The P4
position, distal to the site of hydrolysis, is important in defining substrate
processing by the proteasome. We observed direct correlations between subunit
modification and inhibition of distinct proteolytic activities, allowing the
assignment of activities to individual beta subunits. The ability of
tetrapeptides, but not tripeptide vinyl sulfones, to act as substrates for the
proteasome suggests there could be a minimal length requirement for hydrolysis by
the proteasome. These studies indicate that it is possible to generate inhibitors
that are largely specific for individual beta subunits of the proteasome by
modulation of the P4 and carboxy-terminal vinyl sulfone moieties.
PMID- 9653550
TI - Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive
forms by a single amino-acid substitution.
AB - BACKGROUND: Specific inhibitors of protein kinases have great therapeutic
potential, but the molecular basis underlying their specificity is only poorly
understood. We have investigated the drug SB 203580 which belongs to a class of
pyridinyl imidazoles that inhibits the stress-activated protein (SAP) kinases
SAPK2a/p38 and SAPK2b/p38 beta 2 but not other mitogen-activated protein kinase
family members. Like inhibitors of other protein kinases, SB 203580 binds in the
ATP-binding pocket of SAPK2a/p38. RESULTS: The SAP kinases SAPK1 gamma/JNK1,
SAPK3 and SAPK4 are not inhibited by SB 203580, because they have methionine in
the position equivalent to Thr106 in the ATP-binding region of SAPK2a/p38 and
SAPK2b/p38 beta 2. Using site-directed mutagenesis of five SAP kinases and the
type I and type II TGF beta receptors, we have established that for a protein
kinase to be inhibited by SB 203580, the sidechain of this residue must be no
larger than that of threonine. Sensitivity to inhibition by SB 203580 is greatly
enhanced when the sidechain is even smaller, as in serine, alanine or glycine.
Thus, the type I TGF beta receptor, which has serine at the position equivalent
to Thr106 of SAPK2a/p38 and SAPK2b/p38 beta 2, is inhibited by SB 203580.
CONCLUSIONS: These findings explain how drugs that target the ATP-binding site
can inhibit protein kinases specifically, and show that the presence of threonine
or a smaller amino acid at the position equivalent to Thr106 of SAPK2a/p38 and
SAPK2b/p38 beta 2 is diagnostic of whether a protein kinase is sensitive to the
pyridinyl imidazole class of inhibitor.
PMID- 9653551
TI - 19F NMR in the measurement of binding affinities of chloroeremomycin to model
bacterial cell-wall surfaces that mimic VanA and VanB resistance.
AB - BACKGROUND: The emergence of bacteria that are resistant to vancomycin, the drug
of choice against methicillin-resistant Staphylococcus aureus, has made the study
of the binding characteristics of glycopeptides to biologically relevant
depsipeptides important. These depsipeptides, terminating in D-alanyl-D-lactate,
mimic the cell-wall precursors of resistant bacteria. RESULTS: The use of 19F
labelled ligands in the study of the therapeutically important vancomycin series
of antibiotics is demonstrated. The substantial simplification of spectra that
occurs when such labelled ligands are employed is used in the measurement of
binding affinities of depsipeptides to chloroeremomycin (CE). Large enhancements
of binding affinities are found at a model bacterial cell-wall surface
(constituted from depsipeptides that are anchored into vesicles) relative to
those measured in free solution. CONCLUSIONS: Surface-enhanced binding,
previously shown for strongly dimerizing glycopeptide antibiotics to normal -D
alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to
the surface of models of VanA- and VanB-resistant bacteria. The effect of
depsipeptide chain length is shown to be critically important in producing and
maximizing this enhancement.
PMID- 9653552
TI - Inhibiting the dimeric restriction endonuclease EcoRI using interfacial helical
peptides.
AB - BACKGROUND: Many enzymes are active only in a dimeric form, including a variety
of type II restriction endonucleases. Disruption of subunit interactions is
therefore a potential method for multimeric enzyme inhibition. EcoRI is a
homodimeric restriction endonuclease, the dimeric interface of which consists of
a four-helix bundle. We set out to design helical peptides to interact with this
interface and block dimer formation, thus rendering EcoRI inactive. RESULTS: Here
we describe two synthetic, helical peptides based on the interfacial region of
EcoRI. Both peptides inhibit the enzyme, but the peptide derived from the alpha 4
helix of EcoRI had both a higher helical content and better efficacy than a
variant peptide, alpha 4(Leu), that has three Ile-->Leu mutations (IC50 values of
27 microM and 90 microM, and helical contents of 29% and 10%, respectively). Size
exclusion chromatography confirmed that the alpha 4 peptide disrupted
dimerization of EcoRI, and circular dichroism indicated that EcoRI remained
folded upon binding to alpha 4. Inhibition with alpha 4 and alpha 4(Leu) was
shown to be specific for EcoRI, as the dimeric restriction enzyme PvuII was not
affected by the peptides. CONCLUSIONS: Interfacial peptide inhibitors of the
dimeric EcoRI were obtained that both inhibit dimerization and endonuclease
activity. The peptide sequence with a preference for a helical conformation was a
more effective inhibitor, presumably because the more preorganized state enhanced
interactions with the helical interface of EcoRI. The specific nature of this
endonuclease-peptide interaction was also confirmed. The potential of this
strategy for inhibiting other enzyme classes is currently being addressed.
PMID- 9653553
TI - Lipitoids--novel cationic lipids for cellular delivery of plasmid DNA in vitro.
AB - BACKGROUND: Although synthetic nonviral vectors hold promise for the delivery of
plasmid DNA, their gene-transfer efficiencies are far from matching those of
viruses. To systematically investigate the structure-activity relationship of
cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids)
was synthesized. The compounds were evaluated for their ability to form complexes
with plasmid DNA and to mediate DNA transfer in vitro. RESULTS: Lipid-peptoid
conjugates were conveniently prepared in high yield using solid-phase synthesis.
Several lipitoids condensed plasmid DNA into 100 nm spherical particles and
protected the DNA and DNase digestion. A subset of lipitoids with a repeated
(aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl
phosphatidyl-ethanolamine (DMPE) mediated DNA transfer with high efficiency.
CONCLUSIONS: Automated solid-phase synthesis of cationic lipids allowed the rapid
synthesis of a diverse set of transfection reagents. The most active compound
DMPE-(Nae-Nmpe-Nmpe)3 (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl
glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic
lipid transfection reagents) and is active in the presence and absence of serum.
The activity in the presence of serum suggests potential for applications in
vivo.
PMID- 9653554
TI - [Recommendations for surgical therapy planning and interventions in patients with
AIDS].
AB - No other disease has exhibited such a significant influence on the behaviour of
health care workers (HCW) as the AIDS pandemic. Numerous epidemiological data,
however, have proven that the overall risk of transmission of the human
deficiency virus (HIV) during surgical interventions is low; it is 0.3% for all
types of percutaneous exposures. Nevertheless, there still is a need for wider
adoption of safer surgical techniques to reduce the chances of HIV transmission
in the operation theatre, which additionally minimize the risk of transmission of
other blood-borne pathogens. In the case of occupational exposure to HIV
contaminated blood or body secretions post-exposure prophylaxis should be
recommended stratified by the type of exposure and source material.
PMID- 9653555
TI - [Transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease].
AB - Different diseases of the transmissible spongiform encephalopathy (TSE) group are
known to affect humans and various animals. Owing to the bovine spongiform
encephalopathy (BSE) epidemic and the description of the new variant of
Creutzfeldt-Jakob disease (nvCJD), which is probably linked to BSE, TSE received
much attention. The nature of the causative agent is still disputed; none of the
proposed concepts (prions, viruses) can explain all features. It is clear,
however, that there is a genetic component in susceptibility to infection and in
development of disease and that transmission may cross the species barrier. This
paper gives an overview of the first results and latest developments of basic TSE
research that has focused on in vivo early diagnosis and the prevention of
possible (also iatrogenic) transmission.
PMID- 9653556
TI - [Surgery in hepatitis].
AB - Viral hepatitis belongs to the most important infectious diseases worldwide. More
than 300 million chronic HBsAg carriers and chronic HCV carriers exist,
respectively. High endemic areas of viral hepatitis are Asia, Africa, Latin
America and the Near, Middle and Far East. Viral hepatitis is also very important
in health care workers. Today viral hepatitis can be differentiated from type A
to type E (G) based on immunological and molecular assays. While enterally
transmitted hepatitis type A and type E only induce acute and rare fulminant
disease, hepatitis type B, C and D often induce chronic progressive disease
including liver cirrhosis with typical complications due to the portal
hypertension and with a high rate of association with the development of primary
liver cancer (HCC). This review focusses on viral hepatitis-related surgical
problems, including liver transplantation.
PMID- 9653557
TI - [Fungal infection].
AB - Untreated dermatological mycoses are easy to diagnose. Once treatment with
corticosteroids has been initiated the diagnosis of a mycosis can be difficult.
In the immunosuppressed patient (AIDS patients) typical dermatological
manifestations can be lacking. Systemic antimycotic therapy requires precise
detection of the pathogen concerned. Mistakes still made in surgical practice are
incision of a tumour in the case of tinea profunda and the extraction of nails
affected by fungi. In the healthy person yeasts are transient organisms present
in the mouth and intestinal tract in contrast, the mouth and intestinal tract of
patients in risk make up a reservoir of candida infection that can affect the
internal organs. Cryptococcosis and aspergillosis are inhaled mycoses. Factors
predisposing to mycoses influence the duration and the outcome of the course of
illness. The most important of these factors in surgical practice is the
immunosuppression. Systemic mycoses are difficult to recognize. In many cases
organ mycoses can be diagnosed by CT. Continuous investigations of diagnostic
cultures and serological tests can contribute to the diagnosis. Only
cryptococcosis can be ascertained early by specific antigen demonstration in the
serum. For this reason continuous serological testing for cryptococci is
essential in AIDS patients.
PMID- 9653558
TI - [Elective early surgery of acute uncomplicated sigmoid diverticulitis--a
dangerous error?].
PMID- 9653559
TI - [Recovery and duration of work disability after laparoscopic and conventional
appendectomy. A prospective randomized study].
AB - To evaluate whether laparoscopic appendectomy shortens the convalescence and the
postoperative period until return to work when compared to conventional
appendectomy, a prospective randomized trial was performed. The major endpoint of
the study was the time until return to work; minor endpoints were postoperative
pain, fatigue, operative time and postoperative morbidity. In all, 54 patients
with a mean age of 29.5 +/- 10.1 years were randomized to open (n = 28) or
laparoscopic appendectomy (n = 26). Age, sex, body mass index (BMI), American
Society of Anesthesiology (ASA) rating, job status as well as histologic degree
of inflammation of the appendix were comparable in the two groups. Operative time
was 59.2 +/- 15.8 min for laparoscopic and 59.8 +/- 24.4 min for conventional
appendectomy (P = 0.9). Some 16 laparoscopic appendectomies (62%) were performed
by board-certified surgeons, while 23 conventional appendectomies (82%) were
performed by residents (P = 0.003). Postoperative morbidity was comparable
between the two groups. After laparoscopic appendectomy, pain was rated
significantly lower on the first, second and fourth postoperative day when
compared to the conventional group. There were no difference in postoperative
fatigue between the groups. Time to return to work was 17.0 +/- 6.2 days in the
laparoscopic group and 18.2 +/- 6.0 days in the conventional group (p = 0.5).
Laparoscopic appendectomy has no advantages in terms of convalescence and time to
return to work when compared to open appendectomy and should therefore be limited
to selected cases.
PMID- 9653560
TI - [Hospitals, university clinics and the work schedule law].
PMID- 9653561
TI - [No access to hospital records to evaluate service misuse].
PMID- 9653562
TI - [Prevention of thromboembolism in surgical practice].
PMID- 9653563
TI - [Missed thrombosis diagnosis--flagrant malpractice? Decision of the Oldenburg
supreme court 25 November 1997--5 U 66/97].
PMID- 9653564
TI - [Why surgeons are accused of malpractice. The American perspective].
PMID- 9653565
TI - [Early morphological changes in Crohn disease as further evidence for
conservative resection indications].
AB - Clinical studies revealed that the size of the margin of resection and the
microscopic findings at the edge of the specimen did not influence the rate of
recurrence. Regarding early lesions of Crohn's disease, the aim of the present
study was to identify morphological alterations which are able to explain the
clinical findings and are in accordance with the operative procedure. In the
present study the resection margins of 29 patients with Crohn's disease were
investigated using the scanning electron microscope. Seventy-three percent of
patients with histopathologically unaffected resection margins in the small bowel
and 71% in the large bowel showed early lesions. These consisted of mucosal
architectural alterations, epithelial bridge formation and goblet cell
hyperplasia and hypertrophy. Curative resection is not possible, independent of
the resection margins. The morphological findings underline the correctness of
the usual operative procedure, namely limited resections in Crohn's disease.
PMID- 9653566
TI - [Techniques of laparoscopic preparation and current-induced complications.
Results of a survey in Germany].
AB - 138 surgical institutions in Germany retrospectively answered a questionnaire on
available energy sources, techniques of preparation and complications due to the
use of electric current in laparoscopic surgery. The median experience in this
field of surgery was 6 years. For common laparoscopic operations the majority of
surgeons use electrosurgery; only 8% never do so. Except in appendectomy,
monopolar cautery is preferred for all operations. Other energy devices are of
minor importance. The overall number of operations reported was nearly 138,000.
The rate of complications due to the use of electric current was 0.1%. This
figure is accounted for in equal part by intra- and postoperative burns. The
complication rate is at the lower end of the range known from the literature.
Even though the retrospective nature of this analysis may hide a certain number
of injuries electric, current plays a minor role for complications in
laparoscopic surgery.
PMID- 9653567
TI - [Dependence of surgical trauma in aortic interventions on the approach chosen. A
prospective study].
AB - Transabdominal aortic replacement is the most widely accepted approach for aortic
surgery. Several controlled studies report a more favorable outcome after an
extraperitoneal incision, yet there are an equal number of papers with
contradictory results. The aim of our study was to assess operative trauma after
aortic surgery, depending on whether transperitoneal or extraperitoneal access
was used. As a parameter for the extent of the surgical trauma the concentration
of Interleukin 6 and acute phase proteins (CRP) was measured pre-, 6 h and 24 h
after aortic surgery. One group consisted of 34 patients scheduled for aortic
surgery for exclusion of an abdominal aortic aneurysm. The second group consisted
of 26 patients who were operated on for aorto-iliac occlusive disease. Each group
was subdivided into an equal group of patients operated on either extra- or
transperitoneally. In the retroperitoneal aneurysm patients, a posterolateral
access was favored, and in patients with occlusive disease an extraperitoneal
anterolateral approach was chosen. As a result patients with an extraperitoneal
incision and aorto-iliac occlusive disease required less postoperative
respiratory support than those operated on transperitoneally. In this subgroup of
patients there was a significantly reduced synthesis of Interleukin 6 and CRP.
When a retroperitoneal posterolateral approach was required in aneurysm patients,
there was no difference between groups. We conclude from our data that only
patients with limited infrarenal aortic access can benefit, from the
retroperitoneal incision in terms of a reduced immunological reaction.
PMID- 9653568
TI - [Ankle para-articular tibial fracture. Is osteosynthesis with the unreamed
intramedullary nail adequate?].
AB - In a prospective study, 53 fractures of the distal fifth of the tibia were
stabilized by unreamed nailing. Additional involvement of the ankle joint
occurred in 18 patients. 50 patients returned for follow-up. In 30 patients tibia
and fibula were fractured at the same (distal) level; in 20 patients the fracture
of the fibula was located more proximally. In 12 patients the fractures extended
into the tibial pilon. Severe soft tissue damage was seen in 24 fractures (18
open, 6 closed). Ninety percent of all fractures healed uneventfully without
further surgical intervention after unreamed nailing. In two patients the
unreamed nail had to be exchanged for a reamed tibial nail. Bone grafting and
secondary dynamization of the nail by removal of a proximal interlocking bolt
were performed in one case each. Thirty-one fractures healed in anatomical
position. Valgus or varsus angulation of less than 5 degrees occurred in 18
patients. One fracture healed with rotatory angulation of 15 degrees. The highest
rate of complications (22%) was seen in patients with distal fractures of the
fibula without additional plating (of the fibula). There was no deep infection.
Tibial fractures close to the ankle joint can be managed by unreamed nailing.
Distal fractures of the fibula should be stabilized by additional plating.
Because of the unreamed technique of implantation this procedure can also be used
in grade II or III open fractures.
PMID- 9653569
TI - [Invagination of the vermiform appendix in mucinous cystadenoma].
AB - Intussusception of the appendix vermiformis in adults is an uncommon event. The
combination of a mucinous cystadenoma with an intussuscepted appendix is
extremely rare. Clinical symptoms are nonspecific; in most cases the correct
diagnosis is not made before surgical exploration. With the radiologic and
endoscopic presentation of a polypoid lesion of the caecum, a neoplasm is often
considered. Endoscopic appendectomy or disinvagination by enema have been
described. Thus the definitive therapy is surgery and depends on the histological
diagnosis.
PMID- 9653570
TI - [Perforated diverticulum of the vermiform appendix].
AB - Diverticulitis of the vermiform appendix is an often disregarded disease.
Diagnosis follows after appendectomy due to inflammatory complications in the
form of diverticulitis and appendicitis. Diverticula can also be found as a
reason for complaints in histologically unaltered appendix or as an incidental
finding. Diverticula of the vermiform appendix are classified as false (acquired)
or true (congenital). We report on the case of a 57-year-old man with a
perforated appendix diverticulum as reason for peritonitis and a paralytic ileus
of the colon and small intestine.
PMID- 9653571
TI - [Superficial femoral vein as vascular graft in surgical therapy of mycotic
aneurysm of the common iliac artery].
AB - A 38-year-old polytoxicomanic male patient developed an occlusion of both
popliteal arteries associated with an aneurysm of the right common iliac artery.
A septic cause was suspected and an antimycotic therapy was instituted, but the
diameter of the aneurysm increased to 3 cm during 6 months. Moreover, multiple
periarterial abscesses occurred. The aneurysm was resected and the iliacal axis
reconstructed in situ, using a superficial femoral vein interposition. Six months
after operation, patency was confirmed by duplex sonography. Phlebodynamic
examinations showed normal flow functions at the donor site.
PMID- 9653572
TI - [Patient motivation--an essential therapeutic tool].
AB - A deciding factor for the future functioning of a hand with a mutilating hand
injury is the self-motivation that the patient brings with him to rehabilitation.
This is illustrated in the case of a guitar teacher who returned to his career
after subtotal and total finger amputation of his left hand (used for gripping
chords). With consistent exercise on his instrument he compensated for the
functional deficits of his hand and won a law suit against his employer who
denied that he had the physical ability to play the classical guitar. It is more
clear than ever that an injured person is jointly responsible, through self
motivation in the working process, for more-or-less complete rehabilitation. It
is not uncommon in a system of job-sharing in which several members of the health
service (surgeons, physiotherapists, social workers, general practitioners) must
co-ordinate their work, for the patient--if he does not involve himself--to fall
by the wayside. It is shown how inherent and rewarding it can be to support the
patient in his desire to return to work. Apart from that, we hope that this
example will be an encouragement to those similarly affected.
PMID- 9653573
TI - [Acute arterial occlusion in an arteriosclerotic vessel].
PMID- 9653574
TI - [Surgical procedure in stomach ulcer and duodenal ulcer].
PMID- 9653575
TI - The lack of circadian timing in two intertidal invertebrates and its significance
in the circatidal/circalunidian debate.
AB - The control of the timing of gaping in the clam Austrovenus stutchburyi does not
involve a circadian mechanism. The lack of a circadian timer is shown by the
uniform pattern in gaping in constant conditions (CC) regardless of the
relationship between the tidal cycle and the day/night cycle at the time of
collection; it is also shown by the fact that, in nontidal conditions, a 24 h
light-dark (LD) cycle fails to entrain persistent rhythmicity. The crab
Macrophthalmus hirtipes also lacks a circadian oscillator. Both of these
intertidal dwellers, however, exhibit endogenous tidal rhythmicity. The features
of the tidal patterns they display in CC can be accounted for using the
circalunidian (i.e., approximately 24.8 h) model of a tidal timing system but, as
they lack circadian timers, cannot be explained by the circatidal (i.e.,
approximately 12.4 h)/circadian model. This demonstrates that, of the two
hypothetical models of the clock system driving endogenous tidal rhythms, only
the circalunidian one has universal applicability.
PMID- 9653576
TI - Circadian rhythm of activity in Japanese quail in constant darkness: variability
of clarity and possibility of selection.
AB - In conditions of constant darkness, interindividual variability in the clarity of
circadian rhythmicity was observed in sexually immature young quail, with birds
classified as more or less rhythmic or arrhythmic. The relative clarity of this
circadian rhythm was observed on the actograms by measurement of the
autocorrelation coefficient ratio over 12 cycles. Autocorrelation coefficients
were calculated from sequential series of total activity over 12-minute periods.
Crosses of selected phenotypes with different clarities of rhythmicity were
conducted in order to study the possibility of selection of this characteristic.
From a random population (N = 42, twice), pairs of the most rhythmic birds (3
families), and pairs of arrhythmic birds (4 families) were reared.
Autocorrelation coefficient ratios of F1 birds from rhythmic families (N = 54)
were greater than those of F1 birds (N = 48) from arrhythmic families (t-test, p
< .0001). These ratios in offspring were significantly correlated with that of
the mean parent of each clutch of siblings (N = 102, r = .35, p = .0003). This
result was maintained in a second generation (F2) of birds, for which significant
differences in expressed rhythmicity were observed. That is, autocorrelation
coefficient ratios of F2 birds from two rhythmic families (N = 30) were greater
than those of F2 birds from arrhythmic families (N = 20) (t-test, p = .039).
Comparison of F2 outbred and inbred birds from rhythmic pairs showed greater
values of autocorrelation coefficient ratios in the case of inbred birds (N = 16)
than for outbred birds (N = 30; t-test, p = .036). There was no difference
between outbred (N = 20) and inbred birds (N = 15) from arrhythmic pairs.
Therefore, selection of a rhythmic strain seems possible, whereas crosses between
two arrhythmic birds may also give rise to rhythmic birds. Comparisons between
rhythmic birds of different families did not show differences in the free-running
period of the circadian rhythm, which is true also for rhythmic birds bred from
two arrhythmic parents. Therefore, our selection procedure did not seem to be
based on the characteristics of the pacemaker itself, but rather on a downstream
event. Although the parents were not selected on the basis of quantity of
activity per cycle or on the duration of the active phase, significant
differences among the offspring of different families were shown.
PMID- 9653577
TI - Aggressive and sexual social stimuli do not phase shift the circadian temperature
rhythm in rats.
AB - The objective of the present study was to determine whether the rat circadian
system is sensitive to social stimuli. Male rats were subjected to a sociosexual
interaction with an estrous female or to an aggressive interaction with a
dominant male conspecific. The interactions lasted for 1 h and took place in the
middle of the circadian resting phase. Control animals were picked up and handled
for a few minutes, but were otherwise left undisturbed. Animals were housed under
constant dim red light during the whole period of the experiment. To assess the
effects of the interactions on free-running circadian rhythmicity, body
temperature was measured by means of radio telemetry. neither the sociosexual
interaction with a female nor the aggressive interaction with another male
induced phase shifts or changes in the free-running period. The rat circadian
system does not seem to be sensitive to social stimuli directly. Moreover, the
finding that aggressive interactions do not phase shift circadian rhythms
indicates that the endogenous pacemaker in rats is not sensitive to stressors.
PMID- 9653578
TI - Rhythmic patterns in incidence of peptic ulcer perforation over 5.5 decades in
Norway.
AB - The incidence of ulcer perforation in 1480 patients treated in the Bergen area of
Norway between 1935 and 1990 was analyzed for daily (circadian), weekly
(circaseptan), and yearly (circannual) time effects. A circadian rhythm was found
overall that was reproducible and fairly stable across seasons, decades, and days
of the week. After subgrouping, a circadian rhythm was found in younger patients,
males, and duodenal perforations, while a 12 h (circasemidian) rhythm
characterized ulcer perforation for women and for gastric ulcers. Duodenal
perforations showed highest incidence in the afternoon, while gastric
perforations showed a major peak around noon and a secondary peak near midnight.
For duodenal ulcer perforation, the circannual pattern was characterized by a 6
month rhythm, with significantly higher incidence in May-June-July and in
November-December in most subgroups. A circaseptan rhythm was not found, but
there was a significantly higher incidence on Thursday-Friday as compared to
Sunday-Monday. The pathophysiological mechanisms underlying the perforation of an
ulcer thus seemed to show pronounced circadian and 6-month rhythmic variations,
much less so circaseptan or circannual rhythms. While it is likely that exogenous
environmental and/or societal factors play a significant role, variations in
ulcer perforation may be related to endogenous biological rhythms in
pathophysiological factors since the circadian pattern of duodenal perforation
follows that for gastric acidity. Knowledge of the temporal patterns in peptic
ulcer perforation and associated pathophysiologic factors should prove useful in
optimizing the chronotherapeutic management of ulcer disease.
PMID- 9653579
TI - Circadian reactions to nCPAP treatment.
AB - To determine possible effects of apnea attacks on the spontaneous behavior of the
circadian system (body temperature, sleeping behavior, vigilance), 11 patients
with obstructive sleep apnea (OSA) were observed before therapy over a 24 h
period under a special constant routine (bed-rest study) and again during therapy
with nCPAP (nasal continuous positive airway pressure). Clinical indicators
(polysomnographical, subjective sleep quality, etc.) indicated successful
therapy. During the bed-rest study with nCPAP therapy, the 24 h amplitude of core
temperature was found to be greater than the amplitude measured before therapy.
Also, therapy decreased sleep disturbances at night and reduced daytime sleeping
times. Consequently, the level of subjective vigilance was higher during the
daytime during therapy. OSA attacks do not only impair sleep; they disturb the
whole circadian system. This may also impair recuperation and sleep. Further
research should test whether measurements of the spontaneous circadian system
could have additional diagnostic value and whether the stabilization of the
circadian system has therapeutic value.
PMID- 9653580
TI - Fall and winter hormone concentrations related to stress in pigs identified as
normal and carrier for stress susceptibility.
AB - Stress is associated with significant losses in the swine industry. Seasonal
changes have been shown to affect stress resistance in several species of
animals. In the present study, we examined the effect of two seasons (fall or
winter) on plasma insulin, cortisol, and adrenocorticotrophin hormone (ACTH)
levels from fasted normal and carrier pigs for stress susceptibility when
submitted to a blood-sampling stressor between 10:00 and 11:00. Comparisons were
made of 10 diurnally active normal (NN) and 8 carrier (Nn) pigs reared in the
fall to 9 NN and 10 Nn pigs reared in the winter. The light-dark cycle throughout
the period of the experiment was 10 h light/14 h dark, with lights on from 07:00
to 17:00. Feed consisted of the traditional western Canadian swine ration
consumed ad libitum. Results revealed significant season-by-genotype interactions
for plasma insulin and ACTH concentrations in response to the blood-sampling
stressor. The normal pigs displayed a significantly lower plasma insulin level
during winter compared to the fall season. Plasma ACTH of normal pigs was 18%
lower in the winter compared to the fall season, although this difference was not
statistically significant. The carrier genotype, on the other hand, demonstrated
higher plasma insulin concentration and lower plasma ACTH concentration in the
winter compared to the fall season. Furthermore, there was a main genotype effect
in plasma cortisol concentration such that the carrier pigs experienced a greater
level compared to the normal genotype. Similarly, the carrier pigs had a more
acute ACTH response to the blood-sampling stressor compared to the normal pigs
during the fall season. Results have demonstrated that these two seasons of the
year affect the response of both genotypes to a blood-sampling stressor, with the
carrier genotype experiencing a more intense stress reaction in the fall season.
These results further contribute to the recent research indicating that carrier
pigs for stress susceptibility have a unique stress response.
PMID- 9653581
TI - Circadian-rhythm-dependent effects of L-NG-nitroarginine methyl ester (L-NAME) on
morphine-induced analgesia.
AB - Circadian changes in the interactions between L-NG-nitroarginine methyl ester (L
NAME), a nitric oxide synthase (NOS) inhibitor, and morphine-induced
antinociception were investigated by the mouse hot-plate test. Both the basal
pain sensitivity and morphine-induced analgesia undergo significant 24 h
variations. L-NAME (40 mg/kg, i.p.) alone did not show any antinociceptive
activity, but potentiated morphine-induced analgesia when combined with morphine
at all injection times. In terms of percentage absolute potentiation (%AP), L
NAME dramatically augmented the analgesic effect of morphine in the late dark
period at 19 hours after lights on (HALO). It is concluded that nitric oxide (NO)
is involved in the modulation of the analgesic effect of morphine; thus, the L
NAME and morphine combination might be beneficial in alleviating pain.
PMID- 9653582
TI - Flow visualization and 1- and 3-D laser-Doppler-anemometer measurements in models
of human carotid arteries.
AB - Pulsatile flow, wall distensibility, non-Newtonian flow characteristics of blood
in flow separation regions, and high/low blood pressure were studied in elastic
silicon rubber models having a compliance similar to human vessels and the same
surface structure as the biological intima models of (1) a healthy carotid artery
model, (2) a 90% stenosis in the ICA, and (3) 80% stenosis in both the internal
and external carotid arteries. Flow was visualized for steady flow and pulsatile
studies to localize flow separation regions and reattachment points. Local
velocity was measured with a 1-, 2-, or 3-D laser-Doppler-anemometer (LDA). Flow
in the unstenosed model was Re = 250. In the stenosed models, the Re number
decreased to Re = 180 and 213 under the same experimental conditions. High
velocity fluctuations with vortices were found in the stenosed models. The jet
flow in the stenosis increased up to 4 m/s. With an increasing bifurcation angle,
the separation regions in the ECA and ICA increased. Increased flow (Re = 350)
led to an increase in flow separation and high velocity shear gradients. The
highest shear stresses were nearly 20 times higher than normal. The 90% stenosis
created high velocity shear gradients and velocity fluctuations. Downstream of
the stenoses, eddies were found over the whole cross-section. In the healthy
model a slight flow separation region was observed in the ICA at the branching
cross-section whereas in the stenosed models, the flow separation regions
extended far into the ICA. We conclude that a detailed understanding of flow is
necessary before vascular surgery is performed especially before artificial
grafts or patches are implanted.
PMID- 9653583
TI - The non-ionic surfactant Poloxamer 188 (RheothRx) increases plasma and whole
blood viscosity.
AB - RheothRx injection is an intravenous formulation of Poloxamer 188, a non-ionic
block copolymer surfactant which is actually used in clinical studies, e.g.,
during thrombolysis in acute myocardial infarction. We have analysed the
influence of RheothRx on plasma and whole blood viscosity of healthy individuals
in vitro. For that purpose plasma was incubated with 0, 0.75, 3.75 and 18.75
mg/ml RheothRx and whole blood with a constant hematocrit of 41.4% with 0, 0.4, 2
and 10 mg/ml RheothRx at 37 degrees C. Viscosity was measured with a Couette
viscometer at shear rates of 94, 11, 0.9 and 0.1 s-1 as well as with a newly
developed oscillating viscometer. In contrast to other studies, we found no
favourable effect of RheothRx on plasma and whole blood viscosity. At the highest
RheothRx concentration an increase in high and low shear viscosity was observed.
Erythrocyte morphology remained unchanged. These data, although on normal blood
in vitro, suggest that the positive effects of RheothRx in vivo may not be caused
by improved flow properties of blood, but could rely on other mechanisms.
PMID- 9653584
TI - Quantitative study of fibrinogen molecules' contribution to the inter-red cells
connections in selected clinical groups of stroke patients.
AB - In a group of 36 patients with acute ischemic stroke, a study of the influence of
arterial hypertension on the red cells and fibrinogen interaction was carried out
by the aspect of fibrinogen molecules' contribution to this phenomenon,
respecting the role of other plasma biochemical factors. Patients were divided
into two clinical groups: with and without arterial hypertension. In the blood
samples with stable haematocrit ratio the following rheological properties were
estimated: plasma viscosity, yield shear stress (YSS), fibrinogen level and
parameter R (the difference between two measurements of fibrinogen
concentration). Also measured were the level of albumin, IgG, IgA, IgM,
cholesterol, HDL and LDL. The value of parameter R in patients with arterial
hypertension was lower than in the group without accompanying disease
(statistical significance was indicated for 80 and 60% of plasma dilution). The
first group of patients was also characterized by a significant increase of IgA
level (in comparison with the control group), whereas the red cells and
fibrinogen interaction measured as a value of YSS was similar in both analysed
clinical groups. This study indicated a specific character of some
hemorheological changes in relation to a certain vascular pathology.
PMID- 9653585
TI - No influence of furosemide on human erythrocyte shape and volume and blood
viscosity in vitro.
AB - Furosemide is a diuretic agent which is often given in high concentration
intravenously. Since erythrocytes have a furosemide-sensitive transport system
and oral application of furosemide was found to induce an echinocytic shape
transformation in horses, we have analysed the influence of furosemide on
erythrocyte shape, volume and blood viscosity in vitro. Increasing plasma
furosemide concentrations of 0, 1, 10, 100 and 1000 micrograms/ml did not affect
the erythrocyte volume or shape and left blood viscosity unaffected. We conclude
that furosemide has no influence on blood rheology in humans.
PMID- 9653586
TI - Systemic sclerosis: blood rheometry and laser Doppler imaging of digital
cutaneous microcirculation during local cold exposure.
AB - A combined study of microcirculation hemodynamics in vivo and blood rheometry has
been carried out in patients with scleroderma compared to primary Raynaud's
phenomenon (PRP) and healthy controls (HC). Laser Doppler perfusion imaging was
used to assess superficial skin blood flow in the fingers before, during and
after local cold exposure. Blood viscosity was measured at 19 and 37 degrees C.
Dynamic and transient flows were also investigated. The scleroderma group showed
a significantly lower level of perfusion before the cold test, that was further
decreased during and after cold exposure, the difference with PRP being maximal
during the rewarming period. It also showed a significantly increased viscosity
(p < 0.05) at low shear rates. Hemorheological behavior of the PRP group was
similar to the HC group. A significant negative correlation between the LDI
perfusion and the apparent blood viscosity at low shear rates was found for the
whole population. These findings suggest that rheological factors may be involved
in the abnormal cold reactivity of patients with scleroderma.
PMID- 9653587
TI - Rheological properties of blood as assessed with a newly designed oscillating
viscometer.
AB - A newly designed type of oscillating viscometer was tested for blood viscosity
measurements. The viscometer consists of a probe (either a tube or a rod)
oscillating at a resonance frequency with amplitudes in the micro- and nanometer
range. The torsional oscillations are dampened by fluids flowing through the tube
or surrounding the rod. The degree of damping depends on the viscosity of the
fluid, which allows to measure viscosity. Data obtained with these instruments
were compared with those obtained with a conventional Couette viscometer. An
increase of erythrocyte aggregation by the addition of dextran 70 in vitro led to
the expected increase of viscosity in the Couette viscometer; in the oscillating
tube viscometer, however, it remained unchanged, which may be explained by a
decreased erythrocyte concentration near the tube wall due to increased
aggregation and flow of erythrocytes in the tube center. In ex vivo experiments
on blood flowing without anticoagulant directly through the tube viscometer an
inverse correlation between viscosity and fibrinogen concentration was found.
This is in contrast to actual knowledge and may indicate that high fibrinogen
levels have a beneficial rheological effect at the tube or vessel wall. Our data
suggest that the new oscillating tube viscometer is an interesting tool, which
may contribute to a more comprehensive understanding of blood flow.
PMID- 9653588
TI - Red blood cell aging and risk of cardiovascular diseases.
AB - We hypothesized that due to monthly bloodloss, the mechanical properties of blood
of premenopausal women are superior to men, and place them at less risk for
cardiovascular diseases than men in any age group. Rheological properties of
blood of premenopausal women and age-matched men were compared. It was found that
male blood possesses an increased viscosity, RBC aggregability and RBC rigidity.
Additionally, male RBCs were found to have higher mechanical fragility. Since
women in reproductive age have almost half as many old RBCs and almost twice as
many young RBCs as men, we investigated the effect of in vivo aging of RBCs on
their mechanical properties. Old RBCs were shown to have an increased mechanical
fragility and aggregability, and decreased deformability as compared to young
RBCs. Decreased deformability and increased aggregability of RBCs cause an
increase in blood viscosity and are known as risk factors of cardiovascular
diseases. Since men possess a higher number of old RBCs with suboptimum
mechanical properties than premenopausal women, who due to monthly bloodloss have
a higher number of young cells and a lower number of old RBCs than their male
counterparts, our results suggest that an elevated hemorheological risk for males
is associated with the age distribution of RBCs. This, in addition to
significantly higher hematocrit, may be the reason for the increased risk of
morbidity and mortality from cardiovascular diseases of men as compared to women
of reproductive age.
PMID- 9653589
TI - An animal model to study erythrocyte senescence with a narrow time window of
erythrocyte production.
AB - Using the method of inducing spherocytic anemia in the rabbit with antibody
serum, we have developed an animal model in which red blood cells (RBCs) can
nearly grow synchronously. With this model, we determined that the surface charge
density on the RBC membrane decreased with cell aging. The change was not linear,
being much more profound in the latter half of RBC life span. There was a
positive correlation between the mean RBC density and its "age" (r = 0.847, p <
0.01). However, the density distribution of the RBCs at the same "age" showed a
broad range, and the density values for RBC groups with different ages showed
considerable overlap. This indicates that the density gradient technique can be
used to separate RBC population into fractions with different mean ages, but has
a low resolving power for obtaining individual RBCs of a given "age".
PMID- 9653590
TI - Natural history of type 2 diabetes in Chinese. Lessons from the islands of
Taiwan.
PMID- 9653591
TI - Application of a diabetes managed care program. The feasibility of using nurses
and a computer system to provide effective care.
AB - OBJECTIVE: Treatment of patients with diabetes often falls short of recommended
process and outcome guidelines. To improve the quality of the provided diabetes
care, a program (the Comprehensive Diabetes Care Service [CDCS]) using a
computerizing tracking and recall system in conjunction with nurses following
protocols was implemented in a managed care setting. The impact of this program
was studied and compared to the care provided to patients in another managed care
setting. RESEARCH DESIGN AND METHODS: Patients followed in the CDCS who completed
a diabetes education course were compared with patients followed in a group model
health maintenance organization (GMH) who also completed a diabetes education
course. CDCS patients received routine care in the program. GMH patients came to
the CDCS yearly to have a diabetes evaluation. A chart review was also performed
on their GMH outpatient records. RESULTS: Initial HbA1c levels were higher in the
CDCS group than in the GMH group (median of 11.9 vs. 10.0%). In the CDCS
patients, HbA1c levels not only fell significantly but were also significantly
lower (P < 0.05) than in the GMH patients during the 2nd and 3rd year of follow
up care. There were no significant changes in HbA1c levels in the GMH patients.
When CDCS patients were divided into compliant and noncompliant patients, the
median HbA1c levels in compliant patients was 8.2%, compared with 11.5% in the
noncompliant group. The CDCS patients who needed treatment for
hypercholesterolemia were more likely to have a lowering of their cholesterol
levels than the GMH patients. All process measures, such as yearly measurement of
HbA1c levels, lipid levels, and foot and retinal exams, occurred much more
frequently in the CDCS patients. CONCLUSIONS: The system developed and
implemented for managing diabetes improved both outcome and process measures. The
comparison group, followed at another managed care setting, received the care
consistent with the average (suboptimal) quality of care provided to patients
with diabetes in the U.S. Therefore, by using innovative systems of management,
the treatment of patients with diabetes can be greatly improved.
PMID- 9653592
TI - Successful treatment with insulin analog lispro in IDDM with delayed absorption
of subcutaneously applied human regular insulin and complicated intraperitoneal
insulin infusion. A case report.
AB - OBJECTIVE: To subcutaneously administer the insulin analog lispro in a patient
with delayed absorption of subcutaneously applied human regular insulin whose
continuous intraperitoneal insulin infusion (CIPII) with a percutaneous access
device had required multiple surgical interventions because of complications.
RESEARCH DESIGN AND METHODS: In a 35-year-old woman with long-term IDDM and
delayed absorption of subcutaneously applied human regular insulin, a 3-year
CIPII with human regular insulin via a percutaneous access device was complicated
by three catheter obstructions and one subcutaneous abscess. Each complication
required the implantation of a new percutaneous access device. During a 2-day
trial with continuous subcutaneous insulin infusion (CSII) of the insulin analog
lispro at basal infusion rates of 0.5-1.1 U/h, stable metabolic control was
achieved. A 5-h intermediate attempt with human regular insulin in CSII, however,
increased blood glucose concentrations from 6.0 to 28.8 mmol/l, despite identical
basal rates and additional injection of 16 U of human regular insulin. Restarting
with CSII of the insulin analog lispro reinforced stable metabolic control.
CONCLUSIONS: It is suggested that the insulin analog lispro is a promising
approach in the treatment of IDDM with delayed absorption of subcutaneously
applied human regular insulin and a suitable alternative therapy for patients
with complications attributed to percutaneous access devices for CIPII.
PMID- 9653593
TI - Development of a scale to measure adherence to self-monitoring of blood glucose
with latent variable measurement.
AB - OBJECTIVE: Adherence to self-monitoring of blood glucose (SMBG) is problematic
for many people with diabetes. Self-reports of adherence have been found to be
unreliable, and existing paper-and-pencil measures have limitations. This study
developed a brief measure of SMBG adherence with good psychometric properties and
a useful factor structure that can be used in research and in practice. RESEARCH
DESIGN AND METHODS: A total of 216 adults with diabetes responded to 30 items
rated on a 9-point Likert scale that asked about blood monitoring habits. In part
I of the study, items were evaluated and retained based on their psychometric
properties. The sample was divided into exploratory and confirmatory halves.
Using the exploratory half, items with acceptable psychometric properties were
subjected to a principal components analysis. In part II of the study, structural
equation modeling was used to confirm the component solution with the entire
sample. Structural modeling was also used to test the relationship between these
components. It was hypothesized that the scale would produce four correlated
factors. RESULTS: Principal components analysis suggested a two-component
solution, and confirmatory factor analysis confirmed this solution. The first
factor measures the degree to which patients rely on others to help them test and
thus was named "social influence." The second component measures the degree to
which patients use physical symptoms of blood glucose levels to help them test
and thus was named "physical influence." Results of the structural model show
that the components are correlated and make up the higher-order latent variable
adherence. CONCLUSIONS: The resulting 15-item scale provides a short, reliable
way to assess patient adherence to SMBG. Despite the existence of several aspects
of adherence, this study indicates that the construct consists of only two
components. This scale is an improvement on previous measures of adherence
because of its good psychometric properties, its interpretable factor structure,
and its rigorous empirical development.
PMID- 9653594
TI - Beginning insulin treatment of obese patients with evening 70/30 insulin plus
glimepiride versus insulin alone. Glimepiride Combination Group.
AB - OBJECTIVE: This study tested a simple algorithm for beginning insulin for obese
patients with type 2 diabetes after sulfonylurea failure, comparing suppertime
70/30 insulin plus continued glimepiride with insulin alone. RESEARCH DESIGN AND
METHODS: This was a multicenter ambulatory randomized double-masked parallel
comparison. There were 208 subjects with secondary failure to sulfonylureas who
took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting
plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were
randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24
weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting
capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl
(7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum
insulin and lipids, and adverse events. RESULTS: FPG and HbA1c were equivalent at
baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24
weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6
mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control
improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less
insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other
respects. No subject had severe hypoglycemia. CONCLUSIONS: Injection of 70/30
insulin before supper safely restored glycemic control of type 2 diabetes not
controlled by glimepiride alone. Control was restored more rapidly and with less
injected insulin when glimepiride was continued.
PMID- 9653595
TI - An Asian multicenter clinical trial to assess the efficacy and tolerability of
acarbose compared with placebo in type 2 diabetic patients previously treated
with diet. Asian Acarbose Study Group.
AB - OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus
placebo during a 24-week treatment period in Asian type 2 diabetic patients with
dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period,
126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/-
SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n
= 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at
week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit,
body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and
24, fasting plasma glucose and insulin were measured before and 1 h after the
administration of an individually tailored breakfast. RESULTS: Using the
intention-to-treat analysis, there were greater reductions in (mean [95% CI])
HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma
glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1
h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P =
0.05) in the acarbose group compared with the placebo group. With acarbose
treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the
placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [
2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of
flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group.
Using baseline HbA1c and race as covariates, there were no significant
interethnic differences in treatment responses (P = 0.232 for treatment-race
interaction; P < 0.001 for treatment effect). The dropout rates were similar
between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no
significant laboratory adverse events in either group. CONCLUSIONS: In this
multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an
effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic
patients with dietary failure. In some patients with troublesome gastrointestinal
symptoms, a lower dosage may be necessary.
PMID- 9653596
TI - Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult
Turner's syndrome. The impact of sex hormone replacement.
AB - OBJECTIVE: To examine glucose metabolism, blood pressure, physical fitness, and
lipid metabolism in adult untreated women with Turner's syndrome compared with a
group of normal women and to examine the effects of female sex hormone
substitution on these factors. RESEARCH DESIGN AND METHODS: A total of 26
patients with Turner's syndrome were examined before and during sex hormone
replacement with 17 beta-estradiol and norethisterone, and an age-matched control
group (n = 24) was examined once. A frequently sampled intravenous glucose
tolerance test was applied with minimal model assessment. We also performed an
oral glucose tolerance test, measurement of 24-h ambulatory blood pressure, and
assessment of physical fitness and lipid metabolism. RESULTS: Insulin sensitivity
(SI) and glucose effectiveness (SG) were similar in Turner's syndrome patients
and control subjects, whereas the acute insulin response (P = 0.03) was lower in
Turner's syndrome patients, and no change was seen during sex hormone treatment.
Abnormal glucose tolerance was found in 50% of Turner's syndrome patients before
and 78% during treatment with sex hormones. Fat-free mass (FFM; P = 0.0005) and
physical fitness (P = 0.002) were lower in Turner's syndrome subjects compared
with control subjects. During treatment, an increase in FFM (P = 0.001) and
physical fitness (P = 0.02) was seen in Turner's syndrome patients. Blood
pressure was increased in Turner's syndrome, and a decrease was seen in diastolic
blood pressure during treatment with sex hormones. CONCLUSIONS: Turner's syndrome
is associated with glucose intolerance, diminished first-phase insulin response,
elevated blood pressure, reduced FFM, and physical fitness. Sex hormone
administration causes a deterioration in glucose tolerance, increases FFM and
physical fitness, and has beneficial effects on blood pressure. The deleterious
effect on glucose tolerance may be mediated by norethisterone, a gestagen known
to have androgenic effects.
PMID- 9653597
TI - Multicenter study of the incidence of and predictive risk factors for diabetic
neuropathic foot ulceration.
AB - OBJECTIVE: To investigate longitudinally prognostic factors for foot ulceration
in a large population of diabetic patients with established neuropathy. RESEARCH
DESIGN AND METHODS: A double-blind multicenter study of a potential new agent for
diabetic neuropathy provided the opportunity for this 1-year investigation since
intervention demonstrated no efficacy in the condition. A total of 1,035 patients
with NIDDM and IDDM were included. Inclusion criteria were vibration perception
threshold (VPT) at the great toe > or = 25 V in at least one foot and < or = 50 V
in both feet, normal peripheral circulation, and no previous foot ulceration. VPT
and clinical components of the Michigan diabetic polyneuropathy (DPN) score were
assessed at baseline and subsequent visits. RESULTS: After 1 year, the incidence
of first foot ulcers for the total population was 7.2%. Neuropathy parameters
were the same between the treatment and placebo groups at baseline and were
unchanged at 1 year; therefore, baseline data were combined for multiple
regression analysis. VPT, age, and Michigan DPN scores for muscle strength and
reflexes were significant independent predictors for first foot ulceration (P <
0.01). For each 1-U increase in VPT values at baseline, the hazard of the first
foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength
and reflex components of the Michigan DPN scores, the hazard of the first foot
ulcer increased by 5.0%. CONCLUSIONS: Tests of VPT and Michigan DPN scores for
muscle strength and reflexes are useful clinical predictors for foot ulceration
in diabetic patients with established neuropathy. The rate of subsequent
ulceration in the following year was alarmingly high, however, despite
standardized foot care education at baseline and regular follow-up visits.
PMID- 9653598
TI - Proteinuria is still useful for the screening and diagnosis of overt diabetic
nephropathy.
AB - OBJECTIVE: To assess the performance of urinary total protein measurements in
timed 24-h urine collection (24-h UP) and in a diurnal random urine specimen
(RUS) for the screening and diagnosis of overt diabetic nephropathy. RESEARCH
DESIGN AND METHODS: A total of 167 diabetic patients (20 type 1 and 147 type 2
diabetic patients; 78 women and 89 men), aged 20-84 years, collected 217 timed 24
h urine specimens. Albumin was measured by immunoturbidimetry, total protein by
sulfosalicylic acid technique, and creatinine by Jaffe's method. According to the
timed 24-h urinary albumin excretion rate (UAER), samples were divided into three
groups: normoalbuminuric (NORMO) (UAER < 20 micrograms/min; n = 84),
microalbuminuric (MICRO) (UAER 20-200 micrograms/min; n = 78), and
macroalbuminuric (MACRO) (UAER > or = 200 micrograms/min; n = 55). Eighty-six
patients also collected 105 RUSs (NORMO, n = 47; MICRO, n = 37; MACRO, n = 21),
and urinary protein concentration (UPC) and urinary protein-to-creatinine ratio
(UPCR) were measured. The receiver operating characteristics (ROC) curve approach
was used to analyze the performance of the diagnostic tests. RESULTS: Spearman's
coefficient of correlation of 24-h UAER versus 24-h UP was 0.95 (P < 0.001), and
of 24-h UAER versus UPC and UPCR were 0.77 and 0.72, respectively (P < 0.001).
The calculated areas (+/- SEM) under the ROC curve for the diagnosis of over
diabetic nephropathy were 0.9987 +/- 0.001 for 24-h UP, 0.9926 +/- 0.006 for UPC,
and 0.9751 +/- 0.014 for UPCR. In the ROC curves, the first points with 100%
sensitivity were 541 mg (95.7% specificity) for 24-h UP, 431 mg/l (92.9%
specificity) for UPC, and 0.2 (76.2% specificity) for UPCR. CONCLUSIONS:
Measurements of proteinuria presented almost perfect accuracy for the screening
and diagnosis of overt diabetic nephropathy. Protein measurement in spot urine is
a reliable and simple method for the screening and diagnosis of overt diabetic
nephropathy.
PMID- 9653599
TI - High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients.
Risk analysis.
AB - OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30
years) can develop diabetic end-stage renal failure (ESRF) in their thirties,
this study was performed to elucidate the incidence and determinants for the
development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence
of diabetic nephropathy and its relationship to baseline characteristics and long
term metabolic control were determined in 426 early-onset Japanese NIDDM patients
who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41
developed diabetic nephropathy manifested by persistent proteinuria (incidence
rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean
HbA1c (measured by a high-performance chromatography method that is standardized
and comparable to the one used in the Diabetes Control and Complications Trial
study) was around 7% or less, few developed nephropathy. The incidence of
nephropathy increased with increasing mean HbA1c level in a dose-dependent manner
(chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of
diabetes at entry had significant predictive effects independent of metabolic
control. CONCLUSIONS: The incidence rate of diabetic nephropathy in early-onset
Japanese NIDDM patients is potentially high, similar to or higher than that in
Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic
nephropathy in NIDDM patients aged in their thirties or forties is likely to be
an early feature that leads to ESRF, and this would contribute to the marked
increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a
serious disease if near-normal glycemia is not achieved.
PMID- 9653600
TI - Asp905Tyr polymorphism of the gene for the skeletal muscle-specific glycogen
targeting subunit of protein phosphatase 1 in NIDDM.
AB - OBJECTIVE: To clarify the contribution of the Asp905Tyr polymorphism of the
muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PP1G) to
insulin resistance and related diseases. RESEARCH DESIGN AND METHODS: We
investigated the Asp905Tyr polymorphism of the PPP1R3 gene, which encodes the
muscle-specific glycogen-targeting subunit of PP1G, in 259 Japanese patients with
NIDDM and 194 healthy control subjects. RESULTS: No significant difference was
found in the genotype distribution between NIDDM patients (N = 259; Asp/Asp =
0.10, Asp/Tyr = 0.44, Tyr/Try = 0.46) and healthy control subjects (n = 194;
Asp/Asp = 0.13, Asp/Tyr = 0.37, Tyr/Tyr = 0.50) or between patient groups
subdivided by the mode of treatment: NIDDM patients with insulin therapy (Asp/Asp
= 0.14, Asp/Tyr = 0.46, Tyr/Tyr = 0.40) and those without insulin therapy
(Asp/Asp = 0.07, Asp/Tyr = 0.43, Tyr/Tyr = 0.50). However, NIDDM patients with
the Tyr allele, which was previously reported to be associated with insulin
resistance, tended to have lower BMIs than those without this allele (Asp/Asp:
24.5 +/- 1.1 kg/m2, Asp/Tyr: 22.6 +/- 0.4 kg/m2, Tyr/Tyr: 22.8 + 0.3 kg/m2, P =
0.06 by analysis of variance). CONCLUSIONS: These data suggest that the Asp905Tyr
polymorphism of the PPP1R3 gene is not associated with NIDDM or high BMI, both of
which are known to be insulin-resistant states, in the Japanese population.
PMID- 9653601
TI - Diabetes in the African-American Medicare population. Morbidity, quality of care,
and resource utilization.
AB - OBJECTIVE: To determine whether African-American Medicare recipients with
diabetes are at increased risk for morbidity, poor quality of care, and high
resource utilization. RESEARCH DESIGN AND METHODS: We analyzed 1,376 patients
with diabetes who were > or = 65 years of age and in the 1993 Medicare Current
Beneficiary Survey. Morbidity measures were the Katz Index of Activities of Daily
Living, Instrumental Activities of Daily Living, overall health perception,
Charlson Comorbidity Index score, and diabetic complications. Quality of care
standards were glycosylated hemoglobin measurements, ophthalmological visits,
lipid testing, mammography, influenza vaccination, readmission within 30 days of
hospital discharge, and outpatient visits within 4 weeks of hospital discharge.
We stratified Medicare reimbursement by type of service and adjusted for sex,
education, and age in multivariable analyses. RESULTS: Compared with white
patients, African-American patients had worse health perception and lower quality
of care. They were more likely to visit the emergency department and had fewer
physician visits per year. African-Americans had higher reimbursement for home
health services, but total reimbursement was similar after case-mix adjustment.
CONCLUSIONS: Improved access to preventive care for older African-Americans with
diabetes may improve health perception and use of the emergency department. The
potential effect on total reimbursement is unclear. Future policy interventions
to improve quality of care among Medicare patients with diabetes should
especially target African-Americans.
PMID- 9653602
TI - Use of the Physician Insurers Association of America database as a surveillance
tool for diabetes-related malpractice claims in the U.S.
AB - OBJECTIVE: To examine the available national surveillance data on malpractice
claims associated with diabetes and to determine the medical specialties having
the highest number of claims and the classes and costs of filed claims relating
to diabetes. RESEARCH DESIGN AND METHODS: Data was abstracted from the Data
Sharing Reports (DSRs) of the Physicians Insurers Association of America (PIAA),
as well as a search of the PIAA's computerized database for the period spanning 1
January 1985 to 31 December 1996. Data on numbers of claims, medical causes of
loss, indemnity paid, demographics of claimants and physicians, severity, and
medical specialties with diabetes-related claims were available. RESULTS: A total
of 906 diabetes claims were reported to PIAA, and the total indemnity paid was
$26,892,848. A significant downward trend (P = 0.004) was noted for the period
between 1993 and 1996. Diabetes claimants were older and predominantly male,
relative to all claimants. Ophthalmology, internal medicine, and general and
family practice had the highest rates of reported claims at 16.5, 13.6, and 13.4
diabetes claims per 1,000 claims, respectively. Of the diabetes-related injuries,
44% occurred in the practitioners office, as compared with 27% for all claims. A
greater proportion of diabetes claims were associated with the highest level of
severity of injury with respect to all claims compiled by the PIAA. CONCLUSIONS:
The database of the PIAA can be a useful resource to monitor trends in diabetes
related malpractice. Further study into whether claims result from lack of
adherence to practice guidelines is needed. Prevention programs designed to
reduce the liability among high-risk specialties may also lead to improved care
for the patient with diabetes.
PMID- 9653603
TI - Comparison of the seasonal pattern in the clinical onset of IDDM in Finland and
Sardinia.
AB - OBJECTIVE: To examine the seasonal pattern for the clinical onset of IDDM in
Finland and Sardinia, two areas where the incidence of IDDM is the highest in the
world, and to determine the effect of climate and temperature on the clinical
onset of IDDM. RESEARCH DESIGN AND METHODS: Analysis of seasonality for the
diagnosis of IDDM was based on 1,405 cases in Finland and 425 cases in Sardinia
diagnosed at < or = 14 years of age from 1989 to 1992. The average annual
incidence of IDDM was 36.4/100,000 in Finland and 34.4/100,000 in Sardinia.
Seasonal patterns were estimated presenting the data as short Fourier series up
to three harmonics together with a possible linear trend. Likelihood ratio tests
and Akaike's information criterion were used to determine the number of harmonics
necessary to model the seasonal pattern. Seasonal patterns in both countries were
compared between sexes and between the three 5-year age-groups, each controlling
for the other's effect. RESULTS: In both countries, a significant seasonal
pattern during a calendar year was found for the sexes combined and for two age
groups (0-9 and 10-14 years). In Sardinia, two distinct cycles were found in the
younger age-group, with a decreased incidence during May through August and an
increased incidence during the autumn months. Two cycles were apparent in the
older age-group, with the nadir occurring during June through September. In
Finland, one cycle was found in the younger age-group, with a decreased incidence
in June. In the older age-group, there were two distinct cycles, with a decreased
incidence in June and in the September through December period. CONCLUSIONS:
Differences between Finland and Sardinia in the seasonal pattern for the
incidence of newly diagnosed IDDM cannot be explained by differences in climate,
temperature, a longer warm period in Sardinia, or other climatic phenomena. The
results do not provide evidence in favor of a specific viral etiology of IDDM. It
may be suggested that there are triggering events at certain times, but they are
likely to be unspecific. Nevertheless, why the incidence of IDDM in these two
populations is equally high despite differences in climate, environment, and
genetic background remains an unsolved question.
PMID- 9653604
TI - Comorbidity of diabetes and eating disorders. Does diabetes control reflect
disturbed eating behavior?
AB - OBJECTIVE: This multicenter study was designed to explore the prevalence of
clinical and subclinical eating disorders (EDs), the extent of intentional
omission of insulin and oral antidiabetic agents, and its relationship to
glycemic control in an inpatient and outpatient population of men and women with
type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Data have been collected
from 12 diabetes medical centers in two German cities. In a questionnaire and
interview-based study, a sample of male and female patients (n = 341 type 1, n =
322 type 2) was assessed for the following eating disorders: anorexia nervosa,
bulimia nervosa, binge eating disorder, and eating disorder not otherwise
specified. For lack of interview data of several patients meeting the screening
criteria, prevalence ranges were calculated. RESULTS: The overall prevalence
range of current EDs was 5.9-8.0% (lifetime prevalence 10.3-14.0%). When patients
were stratified according to type 1 and type 2 diabetes, there was no difference
in prevalence of EDs. However, the distribution of the EDs was different in both
types of diabetes, with a predominance of binge eating disorder in the type 2
diabetes sample. Type 1 (5.9%) and type 2 (2.2%) diabetic patients reported
deliberate omission of hyperglycemic drugs (insulin or oral agents) in order to
lose weight. Compared with control subjects, neither the presence of EDs nor
insulin omission influenced diabetic control. CONCLUSIONS: There seems to be no
difference in prevalence rates of EDs in both types of diabetes; however,
distribution of EDs is different. The findings suggest that neither EDs nor
insulin omission are necessarily associated with poor control of glycemia. Binge
eating disorder seems to precede type 2 diabetes in most patients and could be
one of the causes of obesity that often precedes type 2 diabetes.
PMID- 9653605
TI - Postmenopausal estrogens and risk of myocardial infarction in diabetic women.
AB - OBJECTIVE: The effect of hormone replacement therapy on the risk of myocardial
infarction in diabetic women has not been well studied. We conducted a case
control study of postmenopausal estrogen use and risk of incident myocardial
infarction (MI) in pharmacologically treated diabetic women enrolled at Group
Health Cooperative of Puget Sound, a large health maintenance organization in the
state of Washington. RESEARCH DESIGN AND METHODS: Case subjects (n = 212) were
all postmenopausal women with treated diabetes who sustained an incident fatal or
nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were
treated diabetic women drawn from a stratified random sample of postmenopausal
women without prior MI. Computerized pharmacy data and medical records were used
to measure use of estrogens. Cardiovascular risk factors recorded from medical
records, computerized pharmacy and laboratory data, and telephone interviews were
used as adjustment variables. RESULTS: In this study 8.5% of case and 13.9% of
control subjects were current users of estrogens. The relative risk (RR) of MI
for current estrogen users was 0.51 (95% CI 0.22-1.15) relative to never users,
adjusted for age, study year, weight, angina, and duration of treated diabetes.
Among current estrogen users, risk of MI tended to decline with each additional
year of estrogen use (adjusted RR = 0.78, 95% CI 0.56-1.08). Of those studied,
45.3% of case and 37.7% of control subjects were past users of estrogens
(adjusted RR = 1.22, 95% CI 0.71-2.09). CONCLUSIONS: This study suggests that use
of postmenopausal estrogens does not increase risk of MI in diabetic women and
that sustained use may be of benefit.
PMID- 9653606
TI - Direct medical costs of complications resulting from type 2 diabetes in the U.S.
AB - OBJECTIVE: To estimate direct medical costs of managing the complications of type
2 diabetes. RESEARCH DESIGN AND METHODS: Costs were estimated for 15 diabetic
complications by applying unit costs to typical resource-use profiles. Resource
used and unit costs were estimated from many sources, including acute care
discharge databases, clinical guidelines, government reports, fee schedules, and
peer-reviewed literature. For each complication, the event costs are those
associated with resource use that is specific to the acute episode and any
subsequent care occurring in the 1st year. State costs are the annual costs of
continued management. All costs are expressed in 1996 U.S. dollars. RESULTS: As
expected, the more severe or debilitating events, such as acute myocardial
infarction ($27,630 event cost; $2,185 state cost), generate a greater financial
burden than do early-stage complications, such as microalbuminuria ($62 event
cost; $14 state cost). Yet, complications that are initially relatively low in
cost (e.g., microalbuminuria) can progress to more costly advanced stages (e.g.,
end-stage renal disease, $53,659 state cost); therefore, minor complications
should also be considered in any economic analysis of diabetes. CONCLUSIONS: The
recent literature has lacked cost estimates that may be readily translated into
patient-level cost inputs for an economic model. Emerging therapies that may
reduce the incidence of some diabetic complications will need to be scrutinized
economically in today's cost-conscious environment. The cost estimates from this
study provide one piece of the economic analysis needed to evaluate these new
interventional therapies.
PMID- 9653607
TI - Association of Helicobacter pylori infection with cardiovascular and
cerebrovascular disease in diabetic patients.
AB - OBJECTIVE: Infection by Helicobacter pylori has been epidemiologically linked to
some extradigestive conditions, including ischemic heart disease. Diabetic
patients are an at-risk population for cardiovascular and thrombo-occlusive
cerebral disease. The aim of the study was to examine a possible relationship
between H. pylori infection and cardiovascular or cerebrovascular disease in
diabetic patients. RESEARCH DESIGN AND METHODS: This was a cross-sectional case
control study with 127 diabetic patients (both IDDM and NIDDM). Special emphasis
was placed on the detection of clinical macro- and microvascular complications,
cardiovascular risk factors, acute phase reactants, and serological markers of
increased cardiovascular disease risk. H. pylori infection was assessed through
the determination of specific Ig-G titers, measured by a commercial enzyme-linked
immunosorbent assay. RESULTS: Coronary heart disease was more prevalent in
diabetic patients with than without H. pylori (odds ratio [OR] 4.07; 95% CI 1.21
13.6; P < 0.05). A history of thrombo-occlusive cerebral disease was also more
frequent in H. pylori-positive diabetic patients (OR 4.8; 95% CI 1.24-18.51; P <
0.05). Other complications such as peripheral arteriopathy, advanced nephropathy,
neuropathy, or retinopathy were no differently distributed according to
serological status. Alterations in the levels of the following acute-phase
reactants and blood chemistry determinations were significantly more profound in
H. pylori-positive diabetic patients: high fibrinogen (P < 0.05), high
erythrocyte sedimentation rate (P < 0.001), high triglycerides (P < 0.001), and
low HDL cholesterol (P < 0.001). There values were also more deeply altered in H.
pylori-positive diabetic patients with a history of coronary heart disease,
thrombo-occlusive cerebral disease, or both, when compared with H. pylori
positive diabetic patients without those complications. CONCLUSIONS: Our data
indicate a possible association of H. pylori infection and the development of
coronary heart disease, thrombo-occlusive cerebral disease, or both, in diabetic
patients. The importance of this link is highlighted by the possibility of an
effective intervention against H. pylori infection.
PMID- 9653608
TI - Usefulness of revised fasting plasma glucose criterion and characteristics of the
insulin response to an oral glucose load in newly diagnosed Japanese diabetic
subjects.
AB - OBJECTIVE: To examine the usefulness of the revised criterion for fasting plasma
glucose (FPG) in the diagnosis of diabetes recommended by the American Diabetic
Association (ADA) (126 mg/dl, 7 mmol/l), and to characterize insulin response
during the 75-g oral glucose tolerance test (OGTT) in newly diagnosed Japanese
diabetic subjects. RESEARCH DESIGN AND METHODS: A series of 2,121 Japanese
subjects underwent a 75-g OGTT (0-3 h) and were divided into three groups (normal
glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes mellitus
[DM] according to the current World Health Organization criteria. After the
cutoff values of FPG that distinguish NGT and IGT from diabetes were analyzed,
the usefulness of the ADA criterion for FPG was examined by comparing diagnostic
parameters (sensitivity, specificity, and accuracy) with those for the cutoff
value of 140 mg/dl. To assess insulin response, both the insulinogenic index
(IsIx), a marker of early secretion, and the area under the insulin response
curve (AUCins), a marker of total secretion, were compared between the DM, NGT,
and IGT groups. RESULTS: First, the FPG cutoff value distinguishing NGT from
diabetes was 109 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs.
0.31), the same specificity (1.00), and a higher accuracy (0.82 vs. 0.74) than an
FPG of 140 mg/dl, and it had a higher specificity (1.00 vs. 0.86) with a slightly
lower accuracy (0.82 vs. 0.85) than an FPG of 109 mg/dl. Second, the FPG cutoff
value differentiating IGT from diabetes was 113 mg/dl. An FPG of 126 mg/dl showed
a higher sensitivity (0.52 vs. 0.31) and accuracy (0.80 vs. 0.74) and a similar
specificity (0.97 vs. 1.00) compared with an FPG of 140 mg/dl, and it had a
higher specificity (0.97 vs. 0.82) with the same accuracy (0.80) as an FPG of 113
mg/dl. Third, the DM group showed the lowest IsIx among the three groups at all
FPG values. The AUCIns in the DM group increased along with FPG, reached the
maximum level at an FPG of 110 mg/dl, and declined thereafter. AUCIns was higher
in the DM group than in the NGT group at FPG values > or = 100 mg/dl.
CONCLUSIONS: The revised ADA criterion for FPG of 126 mg/dl may improve
diagnostic sensitivity without loss of specificity in Japanese diabetic subjects
when compared with an FPG criterion of 140 mg/dl. Although early insulin
secretion was impaired, total insulin secretion did not seem to be reduced in
newly diagnosed Japanese diabetic subjects.
PMID- 9653609
TI - Mortality in adults with and without diabetes in a national cohort of the U.S.
population, 1971-1993.
AB - OBJECTIVE: To examine 22-year mortality (1971-1993), causes of death, life
expectancy, and survival in a national sample of diabetic and nondiabetic adults
according to age, sex, and race. RESEARCH DESIGN AND METHODS: A representative
national cohort of 14,374 adults aged 25-74 years was identified in 1971-1975 in
the First National Health and Nutrition Examination Survey (NHANES I). Diabetes
was ascertained by medical history interview. The cohort was followed for
mortality through 1992-1993, with verification of vital status for 96.2% (n =
13,830). Causes of death were determined from death certificates. RESULTS:
Diabetic subjects comprised 5.1% of the cohort and accounted for 10.6% of the
deaths. Mortality for diabetic subjects increased from 12.4 per 1,000 person
years for those aged 25-44 years at baseline to 89.7 per 1,000 person-years for
those aged 65-74 years. The age-adjusted mortality rate was 57% higher for
diabetic men than for diabetic women; the rate was 27% higher for diabetic non
Hispanic blacks than for diabetic non-Hispanic whites. Mortality rates were
highest for insulin-treated subjects and for those with > or = 15 years' duration
of diabetes. Diabetes was listed on the death certificate as the underlying cause
of death for only 7.7% of diabetic men and 13.4% of diabetic women. Considering
multiple causes of death, heart disease was listed the most frequently and was
present on 69.5% of death certificates of people with diabetes. Death rates were
higher for diabetic than for nondiabetic subjects in all age, sex, and race
groups. The relative risk of death (diabetic versus nondiabetic subjects)
declined with age from a value of 3.6 for those aged 25-44 years at baseline to
1.5 for those aged 65-74 years. The relative risk was elevated in diabetic
subjects for all major causes of death except malignant neoplasms. Survival of
diabetic subjects was lower than that of nondiabetic subjects in all age, sex,
and race groups. Median life expectancy was 8 years lower for diabetic adults
aged 55-64 years and 4 years lower for those aged 65-74 years. CONCLUSIONS: In
this representative national sample of adults, mortality rates were higher for
diabetic men than for diabetic women and for diabetic blacks than for diabetic
whites. The study confirms the substantially higher risk of death, lower
survival, and lower life expectancy of diabetic adults compared with nondiabetic
adults.
PMID- 9653610
TI - Factors associated with glycemic control. A cross-sectional nationwide study in
2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group.
AB - OBJECTIVE: To determine on a large scale the multiple medical and nonmedical
factors that influence glycemic control in the general population of children
with diabetes, we performed a nationwide French cross-sectional study. RESEARCH
DESIGN AND METHODS: We enrolled 2,579 patients aged 1-19 years with type 1
diabetes of > 1 year's duration. The study was center based: 270 centers were
identified, 206 agreed to participate, and 147 included at least 90% of their
patients. Questionnaires were completed by physicians interviewing patients and
family, and HbA1c measurements were centralized. To identify explanatory
variables for HbA1c level and frequency of severe hypoglycemia, we performed
multiple regression analysis using all the quantitative variables collected and
stepwise logistic regression for the qualitative variables. RESULTS: Mean HbA1c
value for the whole population was 8.97 +/- 1.98% (normal 4.7 +/- 0.7% [SD]).
Only 19 children (0.7%) had ketoacidosis during the 6 months before the study,
whereas 593 severe hypoglycemia events occurred in 338 children (13.8%). Control
was better in university-affiliated hospitals and centers following > 50
patients, reflecting the importance of access to experienced diabetologists.
Children had a mean of 2.3 injections, allegedly performed 2.8 glucose
measurements per day, and were seen an average of 4.6 times per year at the
center. In the multiple regression analysis, 94% of the variance of HbA1c was
explained by our pool of selected variables, with the highest regression
coefficient between HbA1c and age (Rc = 0.43, P < 0.0001), then with daily
insulin dosage per kilogram (Rc = 0.28, P < 0.0001), mother's age (Rc = 0.26, P <
0.0001), frequency of glucose measurements (Rc = 0.21, P < 0.0001), and diabetes
duration (Rc = 0.14, P < 0.0001). Logistic regression identified quality of
family support and dietary compliance, two related qualitative and possibly
subjective variables, as additional explanatory determinants of HbA1c. The
frequency of severe hypoglycemia was 45 per 100 patient-years and correlated with
diabetes duration, but not with HbA1c levels or other variables. CONCLUSIONS:
Although overall results remain unsatisfactory, 33% of studied French children
with type 1 diabetes had HbA1c < 8%, the value obtained in Diabetes Control and
Complications Trial adolescents treated intensively. Diabetes management in
specialized centers should be encouraged.
PMID- 9653612
TI - Rigiscan evaluation of specific nervous impairment in patients with diabetes and
erectile disorders.
AB - OBJECTIVE: A proposed new, minimally invasive, and painless method for studying
impairment of the autonomic system of the penile region in type 2 diabetes
patients. RESEARCH DESIGN AND METHODS: Thirteen subjects were selected from 150
patients with type 2 diabetes and erectile dysfunction who were studied in
accordance with the National Institutes of Health consensus. The 13 subjects
(group A), aged 55 +/- 8 years, had acceptable metabolic control (HbA1c, < 8%);
no arterial or venous diseases or initial Peyronie's disease, as evaluated by
penile Doppler ultrasonography and intracavernous prostaglandin E1 injection; and
penile tumescence at the base (PTB) < 30 mm. Group B consisted of 13 control
subjects with the same characteristics, including mean age (53.1 +/- 9 years),
metabolic control (HbA1c, 7.3 +/- 0.7%), and duration of disease (8.3 +/- 0.7
years), but PTB was > 30 mm. Student's t test was used to evaluate differences in
the results of autonomic cardiovascular tests, somatic tests (vibration
perception threshold [VPT]), and diabetic neuropathy score (DNS) in both groups.
The coefficient of variation of PTB was evaluated using the Rigiscan device
(Dacomed, Minneapolis, MN), and Bayes' test was used to test sensitivity,
specificity, and positive predictive values of the cardiovascular tests. RESULTS:
Patients with PTB < 30 mm had significant (P < 0.05) impairment of
parasympathetic tests (lying to standing, P < 0.02; standing to lying, P < 0.04;
squat test, P < 0.03) compared with subjects with higher PTB values. No
difference in DNS and VPT at the base and tip of the penis was found between the
two groups. The variability of the test is 10% in normal subjects and 15% in both
groups of patients. PTB sensitivity was 54%, specificity 89%, and positive
predictive value 79%. CONCLUSIONS: In patients with diabetes and without vascular
diseases, the PTB evaluated by Rigiscan is related to impairment of the autonomic
nervous system. A PTB value < 30 mm may be considered a useful, noninvasive
marker in studying parasympathetic damage of the penile region.
PMID- 9653611
TI - Acarbose in NIDDM patients with poor control on conventional oral agents. A 24
week placebo-controlled study.
AB - OBJECTIVE: To determine the efficacy of acarbose, compared with placebo, on the
metabolic control of NIDDM patients inadequately controlled on maximal doses of
conventional oral agents. RESEARCH DESIGN AND METHODS: In this three-center
double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic
control despite maximal doses of sulfonylurea and metformin were randomly
assigned to receive additional treatment with acarbose 100 mg thrice daily or
placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was
assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and
insulin levels, and fasting lipid levels. RESULTS: Acarbose treatment was
associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs.
placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3
+/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54
+/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant
difference between the two groups regarding changes in fasting plasma glucose and
lipids or fasting and postprandial insulin levels. Flatulence was the most common
side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on
acarbose had asymptomatic elevations in serum transaminases that normalized in 4
weeks after acarbose withdrawal. Another patient on acarbose developed severe
hypoglycemia; glycemic control was subsequently maintained on half the baseline
dosage of sulfonylurea. CONCLUSIONS: In NIDDM patients inadequately controlled on
conventional oral agents, acarbose in moderate doses resulted in beneficial
effects on glycemic control, especially postprandial glycemia, and mean body
weight. Additional use of acarbose can be considered as a useful alternative in
such patients if they are reluctant to accept insulin therapy.
PMID- 9653614
TI - Effects of diabetes and level of glycemia on all-cause and cardiovascular
mortality. The San Antonio Heart Study.
AB - OBJECTIVE: Although the level of hyperglycemia is clearly a risk factor for
microvascular complications in diabetic patients, its role in macrovascular
complications remains controversial. We followed 4,875 subjects (65% Mexican
American) for 7-8 years to investigate the effects of diabetes and hyperglycemia
on all-cause and cardiovascular disease (CVD) mortality. These end points were
also analyzed according to quartiles of baseline fasting plasma glucose among
diabetic participants. RESEARCH DESIGN AND METHODS: The Cox proportional hazards
model was used to estimate the relative risks (RRs) for all-cause and CVD
mortality. RESULTS: Diabetes was significantly associated with increased all
cause mortality (RR [95% CI] = 2.1 [1.3-3.5] in men; 3.2 [1.9-5.4] in women) and
increased CVD mortality (3.2 [1.4-7.1] in men; 8.5 [2.8-25.2] in women). Among
diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause
mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01)
than those in quartiles 1 and 2 combined. After further adjustment for other
potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all
cause mortality and a 4.9-fold greater risk of CVD mortality than those in
quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol >
6.2 mmol/l were significant predictors of CVD mortality using Cox models.
CONCLUSIONS: We conclude that diabetes is a predictor of both all-cause and CVD
mortality in the general population and that both hyperglycemia and common CVD
risk factors are important predictors of all-cause and CVD mortality in diabetic
subjects.
PMID- 9653613
TI - Optimization of evening insulin dose in patients using the short-acting insulin
analog lispro.
AB - OBJECTIVE: A three-way, crossover, open-label, randomized study was designed to
compare the evening and night (1800-0800) glycemic control when the evening
premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased
by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared
with the control arm on standard premeal human regular insulin and pre-bedtime
NPH insulin. RESEARCH DESIGN AND METHODS: A total of 13 type 1 diabetic patients
who use a premeal plus basal insulin regimen were studied on three separate days,
with identical meals and snacks at the same times on each study day. On the
control study day, patients received human regular insulin before dinner and NPH
at bedtime in their usual doses. On another day, lispro was given before dinner
with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the
third regimen, the lispro and NPH were administered together in their usual dose
before the evening meal by separate injections. The three regimens were tested in
random order. RESULTS: Postprandial (1800-2200) blood glucose concentrations were
lower after reduced-dose lispro compared with human regular insulin (6.0 +/- 0.3
[SEM] vs. 7.4 +/- 0.3 mmol/l, P < 0.05). Nighttime (2400-0400) blood glucose
concentrations were not different (8.6 +/- 0.3 vs. 9.2 +/- 0.3 mmol/l, NS), and
prebreakfast concentrations were also unchanged (7.7 +/- 0.9 vs. 8.7 +/- 0.8
mmol/l) after lispro with increased-dose NPH compared with standard insulin. By
contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose
concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with
dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with
standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did
not differ between study days, but it was more frequent postprandially after
dinner usual-dose lispro plus early NPH (2 vs. 7 patients, P = 0.062).
CONCLUSIONS: With lower mealtime and higher basal bedtime insulin doses, patients
using insulin lispro may be able to gain an overall improvement in evening blood
glucose control without deteriorated nighttime glucose levels. Earlier basal NPH
dosage alone does not ameliorate the nighttime hyperglycemia of short-acting
insulin analog regimens.
PMID- 9653615
TI - Power spectral analysis of heart rate variation in diabetic patients with
neuropathic foot ulceration.
AB - OBJECTIVE: To evaluate the relationship between diabetic autonomic neuropathy and
diabetic neuropathic foot ulceration, we used power spectral analysis (PSA) of
heart rate variation, which provides the accurate simultaneous quantification of
parasympathetic and sympathetic activities, to assess autonomic function in
diabetic patients. RESEARCH DESIGN AND METHODS: We studied 55 NIDDM patients
including 10 diabetic patients without neuropathy, 23 diabetic patients with
neuropathy and no history of foot ulceration, and 22 diabetic patients with
neuropathic foot ulceration. We performed PSA of 100 R-R intervals at rest and
analyzed the results by fast Fourier transformation. RESULTS: The low frequency
(LF) power, which reflects sympathetic activity, and the high frequency (HF)
power, which reflects parasympathetic (vagal) activity, were inversely correlated
with the duration of diabetes and the fasting plasma glucose (FPG) levels. By
multiple regression analysis, the FPG remained with significant influence on both
LF and HF powers. The LF and HF powers were positively correlated with motor
nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) in
the upper and lower limbs and the coefficient of variation of R-R intervals. The
LF and HF powers were significantly reduced in patients with neuropathy and
patients with foot ulceration compared with patients without neuropathy. Although
the median MCV and SCV were similar between diabetic patients with neuropathy and
patients with foot ulceration, both the LF and HF powers were significantly
decreased in patients with foot ulceration compared with patients with
neuropathy. There was no difference in the value of the LF:HF ratio, an index of
sympathovagal balance, among three subgroups. We observed a positive correlation
between LF and HF power in all subjects; however, the LF and HF powers were not
correlated in the subgroups of patients with foot ulceration. CONCLUSIONS: These
results showed that diabetic patients with neuropathic foot ulceration have a
greater impairment in spectral indexes of autonomic activity obtained by PSA than
patients with neuropathy and no history of foot ulceration, whereas no difference
was present in nerve conduction velocities.
PMID- 9653616
TI - Stiffness indexes beta of the common carotid and femoral arteries are associated
with insulin resistance in NIDDM.
AB - OBJECTIVE: To investigate the association between arterial wall stiffness indexes
beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin
resistance in NIDDM subjects in a cross-sectional study. RESEARCH DESIGN AND
METHODS: We evaluated the arterial stiffness indexes beta of CCA and FA using an
ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the
diabetes center in Osaka City University Hospital, compared with 120 age- and sex
matched control subjects. Insulin sensitivity indexes were evaluated using a
euglycemic-hyperinsulinemic clamp. RESULTS: Stiffness indexes beta of both CCA
and FA were significantly higher in NIDDM subjects than in control subjects (CCA
18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7
+/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM
subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of
both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r
= -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of
diabetes, and mean blood pressure. In stepwise multiple regression analyses,
insulin sensitivity index and duration of diabetes were identified as significant
independent variables for stiffness indexes beta in both CCA and FA (CCA R2 =
0.249, P = 0.0003; FA R2 = 0.336, P < 0.001). CONCLUSIONS: Arterial stiffness
indexes beta of CCA and FA were associated with insulin resistance in NIDDM
subjects.
PMID- 9653617
TI - Progression to type 2 diabetes among high-risk groups in Kin-Chen, Kinmen.
Exploring the natural history of type 2 diabetes.
AB - OBJECTIVE: To examine the natural history of 654 high-risk subjects (340 men and
314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level
5.6-7.8 mmol/l) who also exhibited 2-h postload glucose concentrations < 11.1
mmol/l and an FPG level < 7.8 mmol/l in a 75-g oral glucose tolerance test
(OGTT). We were particularly interested in comparing the likelihood of developing
type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired
glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively
new definition, and those with PFH used to be defined as NGT according to WHO
criteria. RESEARCH DESIGN AND METHODS: Subjects were located in a 1992-1994
community-based population survey and followed up and reexamined during 1995
1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk
factors predictive of subsequent progression to type 2 diabetes were determined
by comparing baseline variables from the 1992-1994 survey with data of those who
had or had not progressed to type 2 diabetes in 1995-1996. RESULTS: Of 654 high
risk subjects screened in the baseline survey, 481 (73.5%, 255 men and 226 women)
were followed up. Of these, 8.1% had progressed to diabetes (4.1%
progression/year, 95% CI 2.3-5.9). Of 131 baseline IGT subjects, 17.6% progressed
to diabetes (8.8% progression/year, 6.3-11.3), but only 7.4% of 95 PFH subjects
(3.7% progression/year, 2.0-5.4) and 3.5% of 255 NGT subjects (1.8%
progression/year, 0.1-3.0) progressed to diabetes. CONCLUSIONS: The rates of
progression to type 2 diabetes were lowest from the NGT subgroup, highest from
the IGT group, with the PFH group in the middle, suggesting that PFH might be a
transitional condition that precedes IGT and diabetes. Other significant
predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia,
baseline FPG, and 2-h plasma glucose concentration.
PMID- 9653618
TI - Hyperinsulinemia and carotid atherosclerosis in hypertensive and control
subjects.
AB - OBJECTIVE: To analyze the relationships between carotid atherosclerosis measured
as intima-media thickness (IMT) and different measures of insulin in a population
based case-control study of men and women. RESEARCH DESIGN AND METHODS: Carotid
ultrasonographic measurements and 2-h oral glucose tolerance tests were performed
in a random sample of 513 hypertensive subjects, aged 40-59 years, and in 518 age
and sex-matched control subjects. The associations between IMT and the different
measures of insulin were analyzed through multiple regression and by insulin
quintiles. The independent effect of insulin was estimated after concurrent
adjustment for age, obesity, LDL cholesterol, and systolic blood pressure.
RESULTS: The most powerful correlates with IMT were LDL cholesterol, age,
systolic blood pressure, pack-years of smoking, and of the different insulin
parameters, 2-h post-load insulin. In stepwise regression analysis, the
independent predictors of the mean IMT were LDL cholesterol, systolic blood
pressure, pack-years of smoking, and age (P < 0.0001) after adjustment for the
independent predictors. In analysis of variance, no positive association of
insulin parameters with IMT was found between the 2-h insulin quintiles after
adjustment for the independent variables. The exclusion of diabetic subjects did
not change the results. CONCLUSIONS: The present study of a population-based
sample of men and women found inconsistent associations between different insulin
measures and IMT after adjustment for the independent variables.
PMID- 9653619
TI - Glucokinase gene islet promoter region variant (G-->A) at nucleotide -30 is not
associated with reduced insulin secretion in Finns.
AB - OBJECTIVE: To investigate the effect of the islet promoter region variant (G-->A)
at nucleotide -30 of the glucokinase (GCK) gene on insulin levels in subjects
with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM.
RESEARCH DESIGN AND METHODS: The study population included 294 subjects with NGT,
83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests
(OGTTs) were performed in all subjects, and intravenous glucose tolerance tests
(IVGTTs) were performed in subjects with NGT. The islet promoter region of the
GCK gene was amplified with polymerase chain reaction and screened for the
variant (-30) using single-strand conformation polymorphism analysis. RESULTS:
The islet promoter variant (-30) of the GCK gene was found in 17% of subjects
with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between
the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not
differ between subjects with and without this variant in any of the three groups.
Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects
with NGT, did not associate with presence of the islet promoter region variant (
30) of the GCK gene. CONCLUSIONS: These results indicate that the variant (-30)
of the islet promoter region of the GCK gene does not have a significant effect
on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.
PMID- 9653620
TI - International Diabetes Federation meeting, 1997. Neuropathy, information
technology, cost of diabetes care, and epidemiology.
PMID- 9653621
TI - Factor V Leiden (F5 Q506) and vascular disease in Canadian Oji-Cree.
PMID- 9653622
TI - Health-related quality of life and insulin lispro. A naturalistic approach.
PMID- 9653623
TI - Influence of sex differences in subcutaneous fat mass on serum leptin
concentrations.
PMID- 9653624
TI - A simple device for foot pressure measurement. Evaluation in south Indian NIDDM
subjects.
PMID- 9653625
TI - The efficacy of voglibose on glycemic excursions in non-insulin-treated NIDDM
patients.
PMID- 9653626
TI - Freeze-drying of bioproducts: putting principles into practice.
AB - The product and process parameters that determine successful freeze-drying are
described and their interrelationships are explored. It is shown that the
thermochemical and thermomechanical properties of water-soluble, amorphous
materials form the basis of effective formulation design and that coordinated
approaches to formulation and process development achieve optimum results with a
minimum of trial-and-error experimentation.
PMID- 9653627
TI - Application of infrared spectroscopy to development of stable lyophilized protein
formulations.
PMID- 9653628
TI - Water vapor sorption by peptides, proteins and their formulations.
AB - The interactions of pharmaceutical peptides, proteins and their formulations with
environmental water vapor are reviewed. Particular attention is paid to the
importance of the physical structure and chemical diversity of peptides and
proteins, and comparisons are made with the mechanisms of water vapor sorption by
synthetic macromolecular systems. The influences of formulation processes and
additives are also considered and suggestions made for future areas of research.
PMID- 9653630
TI - Sustained release of injectable zinc-recombinant hirudin suspensions: development
and validation of in vitro release model.
AB - In humans, recombinant hirudin (rHir), an anticoagulant protein, has a relatively
short half-life (about 1 h). Therefore, a rHir formulation with sustained
biological activity was previously proposed to result from complexing zinc salts
and rHir (Zn-rHir). The purpose of this paper is to introduce and validate an in
vitro release model for subcutaneous Zn-rHir formulations. In glass vials the
formulations were suspended in agarose gel (2%) and coated with an extra layer of
protein-free agarose. The agarose layers were covered with receiver solution,
either buffered solutions (HEPES or PBS, pH 7.4) or human serum. To validate the
release model and to demonstrate its potential to discriminate between different
formulations, several commercial insulin and Zn-insulin formulations were also
tested. The release profiles were evaluated by statistical moment analysis (mean
times). Only in HEPES buffer was good discrimination between the investigated
insulin formulations observed. The mean times of in vitro release of the insulin
formulations and the proposed duration of their biological activities were in
correlation. Low discrimination was found in PBS. For rHir, clear discrimination
between the investigated rHir formulations was achieved in HEPES buffer, whereas
low discrimination was found in PBS or in serum. The developed release model may
be a sensitive in vitro test to assure the quality of subcutaneous insulin and
rHir formulations, and may also be applicable to assess other slow-release
protein and low molecular weight drug injectables.
PMID- 9653629
TI - Effect of process conditions on recovery of protein activity after freezing and
freeze-drying.
AB - The objective of this research was to gain a better understanding of the degree
to which recovery of activity of model proteins after freeze-drying can be
maximized by manipulation of freeze-dry process conditions in the absence of
protective solutes. Catalase, beta-galactosidase and lactate dehydrogenase (LDH)
were used as model proteins. All of the three proteins exhibited a concentration
dependent loss of activity after freezing, with significantly higher recovery at
higher concentration. The freezing method and the type of buffer were also
important, with sodium phosphate buffer and freezing by immersion of vials in
liquid nitrogen associated with the lowest recovery of activity. Differential
scanning calorimetry was predictive of the onset of collapse during freeze-drying
only for beta-galactosidase. For the other proteins, either no Tg' transition was
observed, or the apparent glass transition did not correlate with the
microscopically-observed collapse temperature. The time course of activity loss
for beta-galactosidase and LDH was compared during freeze-drying under conditions
which produced collapse of the dried matrix and conditions which produced
retention of microstructure in the dried solid. Recovery of activity decreased
continuously during primary drying, with no sharp drop in recovery of activity
associated with the onset of collapse. The most important drying process variable
affecting recovery of activity was residual moisture level, with a dramatic drop
in activity recovery associated with residual moisture levels less than about
10%.
PMID- 9653631
TI - Labelling peptides with fluorescent probes for incorporation into degradable
polymers.
AB - Two peptides, atrial natriuretic peptide (ANP) and salmon calcitonin (sCT) were
conjugated with a fluorescent, amine-reactive probe 5-(and 6
)carboxytetramethylrhodamine,-succinimidylester (5-(6)-TAMRA-SE). The labelling
reaction was followed by HPLC and found to be complete after 2 h. The labelled
peptides were purified by gel filtration chromatography and characterised by
[1H]NMR, UV/VIS and fluorescence spectroscopy. NMR-spectra confirmed the
conjugation of dye to the peptides. Two absorption maxima between 500 and 600 nm
were recorded in the UV/VIS-spectra. The fluorescence spectra were found to be pH
dependent, which allowed the measurement of pH in aqueous solution. The labelled
peptides were encapsulated into poly(lactic acid) (PLA) microspheres using a
double emulsion technique. Probe attachment permitted location of the peptides in
the polymer.
PMID- 9653632
TI - Fibronectin-binding peptides. I. Isolation and characterization of two unique
fibronectin-binding peptides from gelatin.
AB - Gelatin binds to fibronectin with a high affinity although the fibronectin
binding components have not been located. Fibronectin plays an important role in
tumor cell metastasis and gelatin may have a profound effect on the metastatic
process. In this study, fractionated acid-washed gelatin was cleaved with trypsin
and resultant peptides fractionated by fibronectin-Sepharose affinity
chromatography. After further purification using size exclusion HPLC and then
reverse-phase HPLC, two unique peptides were obtained and sequenced. The binding
affinities of these two peptides to fibronectin were evaluated by an ELISA method
developed during this study and compared with the gelatin. Both possessed
significantly higher binding affinities to fibronectin than gelatin alone.
PMID- 9653633
TI - Protein encapsulation and release from poly(lactide-co-glycolide) microspheres:
effect of the protein and polymer properties and of the co-encapsulation of
surfactants.
AB - Despite the recognised role of the poly(lactide-co-glycolide) (PLGA) in the
encapsulation and release of proteins from PLGA microspheres, the importance that
the characteristics of the protein have in these processes has not yet been
sufficiently investigated. The aim of this work was to study the simultaneous
effect of the protein and PLGA properties and of the microencapsulation process
on the physicochemical and in vitro release characteristics of protein-loaded
PLGA microspheres. Two model proteins of different isoelectric points (pI),
bovine serum albumin (BSA) (pI = 4.6) and lysozyme (LZM) (pI = 11.2), and two
different molecular weights (Mw) of PLGA were selected. Microspheres were
prepared using the water-in-oil-in-water (w/o/w) solvent extraction and the oil
in-oil (o/o) solvent evaporation techniques. Results showed that BSA was
efficiently encapsulated independent of the PLGA Mw, whereas the encapsulation of
LZM was favoured with the low Mw PLGA. The co-encapsulation of a surfactant
(poloxamer 188 or 331) reduced the protein encapsulation efficiency, especially
of BSA. These results suggested that the tensoactive properties of the protein
and its affinity for the PLGA are major determinants of the protein
encapsulation. Both proteins released faster from the microspheres prepared by
the o/o solvent evaporation procedure, with respect to those prepared by the
w/o/w solvent extraction technique. In addition, both polymer Mw and protein type
had an effect on the protein release rate. The release rate of both proteins, in
the absence of a surfactant, was faster from the low Mw PLGA microspheres.
However, the release rate constant was higher for BSA than for LZM irrespective
of the PLGA Mw. In addition, the co-encapsulation of a surfactant led, in most
cases, to a faster release of the encapsulated protein. To conclude, these
results suggest that protein release from PLGA microspheres is not only governed
by the PLGA erosion rate and protein diffusion through the water-filled channels,
but is highly affected by the protein properties and its possible interaction
with PLGA and its degradation products.
PMID- 9653634
TI - Recombinant human erythropoietin (rhEPO) loaded poly(lactide-co-glycolide)
microspheres: influence of the encapsulation technique and polymer purity on
microsphere characteristics.
AB - Recombinant human erythropoietin (EPO) and fluorescein isothiocyanate-labelled
dextran (FITC-dextran) loaded biodegradable microspheres were prepared from
poly(lactide-co-glycolide) (PLG) by a modified spray-drying technique. This
microencapsulation method was compared with the water-in-oil-in-water (w/o/w)
double-emulsion method. As expected, microsphere morphology, particle size and
particle size distribution strongly depended on the production process. The spray
drying method was found to have a number of advantages compared to the w/o/w
double-emulsion technique. The content of residual dichloromethane (DCM) in the
final product was significantly lower in case of the microspheres prepared by
spray-drying. Concerning EPO loaded microspheres, spray-drying yielded higher
encapsulation efficiencies. Although the microspheres obtained by spray-drying
are subjected to intensive mechanical and thermal stress during the preparation,
the amount of aggregates of EPO in PLG microspheres were not increased compared
to the w/o/w technique. Depending on the manufacturing method, addition of cyclic
DL-lactide dimers (referred to as monomers in the following) affected the in
vitro release profiles of EPO and FITC-dextran from PLG microspheres. Using
differential scanning calorimetry it was shown that these low molecular weight
substances only seem to be present inside the microspheres produced by spray
drying. DL-Lactide significantly reduced the initial burst release of both EPO
and FITC-dextran. While the following release period of EPO was not affected by
the DL-lactide content, a more linear FITC-dextran release pattern could be
achieved. It can be concluded that the spray-drying technique provides a number
of advantages compared to the w/o/w method. The modulation of protein release
using low molecular weight additives is of particular interest for parenteral
depot systems.
PMID- 9653635
TI - [Max Weber's disease. Research on the disease and therapeutic management at the
turn of the century].
AB - This article on the German economist and sociologist Max Weber (1864-1920)
continues our pathographic and psychohistoric studies on the interrelations
between his life, his illness, and his work on "Protestantic Ethics and the
Spirit of Capitalism". In a former paper (Frommer u. Frommer, 1993) we focussed
on Weber's definition of modern society as an "iron cage" determined by Western
rationalism. His theory, which shows that this cultural background demands a
great amount of role conformity from the individual, converges with current
psychopathological approaches on the personality of depressed patients. In the
second article we report on results of our research on further personal
documents, and some medical certificates by Weber's physicians. These documents
demonstrate the diagnosis of a severe depression in a narcisstic and hypernomic
personality.
PMID- 9653636
TI - [Development of the AMDP module for identification of obsessive- compulsive
symptoms. Conceptualization and empirical results].
AB - Results of epidemiology and comorbidity studies have recently demonstrated the
psychopathological relevance of obsessive-compulsive symptoms. Therefore the
"Arbeitsgemeinschaft fur Methodik und Diagnostik in der Psychiatrie" (AMDP) has
started to develop a rating scale for a quick and precise assessment of obsessive
compulsive symptoms. The actual version of the scale comprises 20 items on the
dimensions "description", "distress and impairment" and "emotion and cognition".
The results of a first empirical study (n = 137, psychiatric in- and outpatients)
demonstrated excellent internal consistency (Cronbach's alpha = 0.92), a split
half reliability of 0.89 (Spearman-Brown), a test-retest reliability of r = 0.86
and good convergent validity with the Yale-Brown Obsessive-Compulsive Scale (Y
BOCS) and the Hamburger Zwangsinventar (HZI). The factor-analytical distribution
of the 20 items revealed a 4-factor structure of the scale. The results are
presented and their implications on further steps of the development of the scale
are discussed.
PMID- 9653637
TI - [Psychopharmacotherapy in pregnancy and breast feeding].
AB - The primary purpose of this article is to review critically the literature on the
use of psychotropic medications in pregnancy and during breast feeding in order
to suggest strategies for the clinical management of these periods. Use of
psychotropic medications during pregnancy may cause three complications: 1.
teratogenicity, 2. perinatal syndromes (neonatal toxicity), and 3. postnatal
behavioural sequelae (behavioural toxicity). The literature features few well
controlled studies concerning these points, so that the available information
allows only few conclusions. Exposure to certain psychotropic drugs in utero may
increase the risk for some specific congenital anomalies; there is mostly no
strong evidence for behavioural toxicity in children exposed to psychotropic
medications. Use of psychotropic drugs during pregnancy and breast feeding may be
appropriate in many clinical situations and should include thoughtful weighing of
risk of pre- and postnatal exposure versus risk of relapse following drug
discontinuation. The authors try to present disorder-based guidelines for
psychotropic drug use during pregnancy and breast feeding and for psychiatrically
ill women who wish to conceive.
PMID- 9653638
TI - [Coping-oriented group therapy for patients with schizophrenic or schizoaffective
disorders. An exploratory study].
AB - The controlled study presented here was designed to examine the influence of the
degree of structure of a coping-orientated therapy, the changes between the
beginning and the end of therapy concerning satisfaction with therapy,
psychopathology, attitude towards medication, coping behaviour and social
variables, the effects on the days of hospitalisation within one year after the
end of treatment and the relevant variables to predict the outcome twelve months
later. It could be shown that patients in a relatively unstructured supportive
group therapy wished to discuss topics that are very similar to those of coping
orientated therapy, that coping-orientated therapy results especially in an
increase in knowledge about illness and treatment and that the therapeutic
outcome after a one-year period can best be predicted by the degree of active
coping strategies, social adaptation, trust in medication and cognitive
variables.
PMID- 9653639
TI - [The clinical picture and stability of non-cognitive symptoms in patients with
Alzheimer's disease].
AB - The purpose of this study was to investigate noncognitive symptoms in Alzheimer's
disease in order to identify symptom patterns and to study stability of such
patterns prospectively. Furthermore, variables were examined which could be
associated with certain types of symptom patterns or could be predictors of
change of these patterns. Forty-eight patients with the clinical diagnosis of
probable Alzheimer's disease were included in this study and were assessed weekly
over a three-week period. Noncognitive symptoms were rated according to the
Behavioral Abnormalities in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the
Dementia Mood Assessment Scale (DMAS) and to a set of items specifically
assessing misidentifications. By means of principal component factor analysis
different noncognitive symptom patterns were obtained yielding a four-factor
solution. They were mapped as rational domains with respect to clinical
experience: 'depression', 'apathy', 'psychotic symptoms/aggression',
'misidentifications/agitation'. Demographic and clinical variables were not
associated with the factor solutions and did not predict change of the factor
values. The results demonstrate that in Alzheimer's disease there are distinct
noncognitive symptom patterns with at least short-term prospective stability.
None of the examined clinical variables, such as age at entry, the status of the
patients (outpatient or inpatient) or dementia severity, exerted substantial
influence on the noncognitive symptom patterns. Further investigations should
concentrate on the pathological and prognostical correlates of noncognitive
symptom patterns in Alzheimer's disease.
PMID- 9653640
TI - A genome survey for novel Alzheimer disease risk loci: results at 10-cM
resolution.
AB - We completed a systematic survey of the human genome, conducted at an average
resolution of 10 cM, for the identification of simple sequence tandem repeat
polymorphisms (SSTRPs) that target new risk genes for Alzheimer disease (AD) by
virtue of linkage disequilibrium. The efficiency of our association study was
enhanced by genotyping pools of DNA from autopsy-confirmed cases with AD and
matched controls. Allelic associations with AD were observed for 6 of the 391
SSTRPs in the CHLC Human Screening Set/Weber Version 6 (Research Genetics, Inc.,
Huntsville, AL): D1S518, D1S547, D10S1423, D12S1045, D19S178, and DXS1047. These
allelic associations were replicated in an independent sample of autopsied AD
cases and controls recruited from a geographically disparate site. The
association of the large D19S178 alleles with AD appeared to arise from linkage
disequilibrium with the APOE epsilon 4 allele, whose effect on increasing the
risk of AD has been established. None of the remaining SSTRPs was in close
proximity to loci previously reported to influence the risk of developing AD.
Instead, they may identify five novel AD susceptibility loci.
PMID- 9653641
TI - Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of
multiple alternatively spliced isoforms.
AB - Catenins were discovered as proteins that are linked to the cytoplasmic domain of
transmembrane cadherins. Among these junctional plaque proteins are several
members of the Armadillo gene family: beta-catenin, plakoglobin, and p120ctn.
Recently it became clear that some catenins also mediate nuclear signaling. We
performed a detailed analysis of the human p120ctn gene (HGMW-approved symbol
CTNND1) and its transcripts. The human p120ctn gene comprises 21 exons,
potentially encoding up to 32 protein isoforms as products of alternative
splicing. Human isoforms, designated 1 to 4, differ from each other by the start
codon used. Additional isoforms are derived from combinations with alternatively
used exons A (exon 18) and B (20), near the end of the open reading frame, and
also with exon C (11) in the middle of the open reading frame. Hence, the longest
isoform is of type 1ABC and comprises 968 amino acid residues. The functional
consequence of the observed multitude of p120ctn splice variants awaits further
study, but tissue-specific expression was obvious. Further, we demonstrate that
the exon organization, which is not simply related to the Armadillo repeat
structure, is very well conserved between the p120ctn gene and the related ARVCF
gene, but not at all between these two genes and the beta-catenin or plakoglobin
genes. The present data favor the concept that p120ctn is the prototype of a
subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP,
and plakophilins 1 and 2, that are more related to each other than to other
Armadillo proteins.
PMID- 9653642
TI - A transcriptional Map of the FMF region.
AB - Familial Mediterranean fever (FMF) is a recessively inherited disorder
characterized by attacks of fever and serositis, which affects primarily non
Ashkenazi Jews, Armenians, Turks, and Arabs. We present here a transcriptional
map covering the FMF locus that we constructed in the course of the positional
cloning of the gene responsible for this disease. This map was established from a
contig constructed with YAC, BAC, and cosmid clones and covers about 500 kb of
16p13.3. It contains nine transcriptional units corresponding to known genes or
to genes belonging to known gene families, 23 gene fragments characterized by
partial sequences, and an endogenous retrovirus sequence. It thus considerably
increases the number of genes in this interval and improves our knowledge
concerning some of the genes or gene families present in this region. Data
accumulated in this region were also used in a comparative study of different
methods of exon detection.
PMID- 9653643
TI - The complete mitochondrial DNA sequence of the rabbit, Oryctolagus cuniculus.
AB - The nucleotide sequence of the complete mitochondrial DNA (mtDNA) molecule of the
rabbit (Oryctolagus cuniculus, order Lagomorpha) was determined. The length of
the molecule is 17,245 nt, but the length is not absolute due to the presence of
different numbers of repeated motifs in the control region. The organization and
gene contents of the mtDNA of the rabbit conform to those of other eutherian
species. The putative secondary structures of the tRNAs of the rabbit have been
described. These structures as well as the structure of the L-strand origin of
replication comply with those characteristic for eutherians in general. The
compositional differences between the two mtDNA strands have also been detailed.
PMID- 9653644
TI - Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non-Hodgkin
lymphoma and multiple tumor types.
AB - Frequent deletions of the distal region on the long arm of chromosome 6 have been
reported in multiple human tumors including B-cell non-Hodgkin lymphoma (B-NHL),
suggesting the presence of one or more tumor suppressor genes (TSGs) at this
locus. Previously, we identified a region of minimal molecular deletion at 6q25
q27 (RMD-1) in B-NHL cases. To facilitate positional cloning efforts to identify
the RMD-1 TSG(s), a yeast artificial chromosome (YAC) contig consisting of 110
clones was constructed across 6q26-q27 by sequence-tagged site/probe content
mapping. The contig integrates 79 ordered markers including restriction fragment
length polymorphisms, minisatellites, microsatellites, YAC-insert termini,
expressed sequence tags, and known genes. It spans 34 cM and has a minimal tiling
path of approximately 12 clones, covering an estimated 9-14 Mb with nearly every
marker on the map showing at least double linkage to its adjacent markers. Dual
color fluorescence in situ hybridization of selected marker pairs on normal
pachytene chromosome 6 further confirmed the YAC-based mappings. Utilizing a loss
of constitutional heterozygosity assay in the B-NHL tumor panel, 24 additional
6q26-q27 polymorphic markers (21 mapping to the contig) further defined RMD-1
between markers D6S186 proximally and D6S227 distally. The minimal tiling path of
the B-NHL RMD-1 consists of approximately 8 YAC clones, providing a size estimate
of 5-9 Mb. This interval contains, in their entirety, several smaller candidate
TSG critical regions previously delimited in other tumor systems. The AF-6 gene,
mapping within RMD-1, revealed no mutations in a small subset of B-NHL. The
deletion and physical maps presented herein provide a framework for the
identification of the gene(s) involved in B-NHL as well as other malignancies and
diseases mapped to this region and provide the initial reagents for large-scale
genomic sequencing.
PMID- 9653645
TI - Molecular cloning and expression analysis of five novel genes in chromosome 1p36.
AB - The human chromosome 1p36 region displays frequent nonrandom chromosomal
deletions and translocations in a number of human malignancies; these are thought
to inactivate tumor suppressor genes. To identify these putative tumor
suppressors we employed exon trapping, cDNA selection, and zoo blot analysis to
clone five new genes located in 1p36. Two of these represent novel genes and were
designated C1orf1 and xylan 1,4-beta-xylosidase 1 (XBX1). Two further genes
represented new members of known gene families: PTPRZ2 was a tyrosine phosphatase
and FRAP2 represented a FKBP12-rapamycin-associated protein. The fifth gene
identified, ENO1L1, was significantly homologous to c-myc promoter binding
protein, MBP-1, and to enolase 1 (ENO1). It colocalized with alpha enolase (ENO1)
on a single P1 clone. ENO1L1 differed from both ENO1 and MBP-1 in the
organization of its 5' untranslated sequences. Second, MBP-1 contained two single
base insertions not present in either ENO1 or ENO1L1 sequences, which led to a
shift in the MBP-1 reading frame. Expression analysis revealed two brain-specific
transcripts of 7.9 and 6.5 kb for PTPRZ2. In contrast, C1orf1, FRAP2, ENO1L1, and
XBX1 appeared to be expressed ubiquitously in the tissues tested, with transcript
sizes of 4.5, 8.7, 1.75, and 4.5 kb, respectively. Using fluorescence in situ
hybridization, we mapped the five novel genes relative to chromosome 1p36
breakpoints present in three established tumor cell lines and one nontumor cell
line. The karyotypic abnormalities in these cell lines were exploited as
chromosomal landmarks; we could thus show that the telomere to centromere gene
order was PTPRZ2-(MBP-1/ENO1/ENO1L1)-(C1orf1/XBX1)-+ ++FRAP2. The localization of
these genes to a chromosomal region that is prone to deletions in human cancers
makes them potential candidate tumor suppressors.
PMID- 9653646
TI - Structure, organization, and chromosomal mapping of the gene encoding
macrosialin, a macrophage-restricted protein.
AB - Murine macrosialin and its human homologue CD68 are heavily glycosylated
transmembrane proteins expressed specifically in macrophages and macrophage
related cells. Macrosialin is predominantly a late endosomal protein but is also
found on the cell surface where it binds oxidized LDL, an important factor in
atherogenesis. We have cloned and sequenced the murine macrosialin gene (Cd68)
and localized it by linkage analysis to chromosome 11. The gene is 1908
nucleotides long from the start site of transcription to the end of the 3'UTR. It
has six exons, which range in size from 79 to 434 nucleotides. The promoter lacks
a classical TATA box but contains other protein binding sites consistent with
preferential monocyte/macrophage gene expression. Although the function of
macrosialin is unknown, it might play a role in lipoprotein regulation given its
binding of oxidized LDL in vitro and its colocalization to a region on chromosome
11 involved in the control of HDL levels.
PMID- 9653647
TI - Structural organization and sequence of CLN2, the defective gene in classical
late infantile neuronal ceroid lipofuscinosis.
AB - Mutations in the CLN2 gene result in classical late infantile neuronal ceroid
lipofuscinosis (LINCL), a fatal childhood neurodegenerative disease. In this
report, we present the complete sequence of the human CLN2 gene and define its
physical relationship with two other genes that have been previously mapped to
chromosome 11p15. The CLN2 gene consists of 13 exons and 12 introns and spans
6.65 kb. By S1 mapping and primer extension, the 5'-terminus of the CLN2 mRNA was
mapped to 32 nucleotides upstream of the proposed initiation codon. A number of
other elements were found to be located in close proximity to CLN2, including the
gene encoding transcription factor TAFII30, the gene encoding intregrin-linked
kinase, and an approximately 914-bp fragment that is 82% identical to
antithrombin III. In addition, an EST cDNA clone that is transcribed on the
strand opposite to CLN2 and that overlaps a portion of the CLN2 gene was
identified. Finally, a set of primer pairs are presented for the amplification of
the coding sequences, putative promoter, and splice junctions of the CLN2 gene.
Taken together, this information will facilitate the molecular analysis of and
genetic testing for classical LINCL.
PMID- 9653648
TI - Cloning and characterization of ZNF189, a novel human Kruppel-like zinc finger
gene localized to chromosome 9q22-q31.
AB - A 3-kb-long cDNA encoding a Kruppel-like human zinc finger protein was isolated
and mapped to chromosome 9q22-q31. The ZNF189 gene encodes a protein with 16 zinc
fingers at its C-terminus and belongs to the Kruppel-associated box (KRAB)
containing group of zinc finger proteins. Four differently spliced cDNA
transcripts, differing at the 5' coding region where a KRAB A repressor domain is
encoded, were isolated. In addition, Northern blot analysis indicates the
presence of two additional unidentified splice variants. Comparison of cDNA and
genomic sequences shows that the ZNF189 gene spans approximately 11 kb and is
organized into at least four exons, the large 3'-end exon coding for the complete
zinc finger domain and the 3' untranslated region. ZNF189 is expressed in all
tissues and cell types currently investigated, at varying levels, but with a
tissue- or cell-type-restricted expression pattern for the different splice
variants. ZNF189 is conserved in the genome of several mammalian species. Direct
sequencing of the ZNF189 gene in microdissected tumor biopsies of sporadic basal
cell carcinoma and squamous cell carcinoma reveals no mutations in the coding
sequence or at exon/intron boundaries.
PMID- 9653649
TI - Identification and characterization of the gene encoding a second proteolipid
subunit of human vacuolar H(+)-ATPase (ATP6F).
AB - The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in
H+ transport in microvesicles and other acidic organelles. We have cloned the
second human proteolipid of the V-ATPase (designated hATP6F), a homologue of the
Saccharomyces cerevisiae proteolipid VMA16, which is an essential subunit of
yeast V-ATPase. hATP6F is a hydrophobic protein with five putative transmembrane
segments, having 61% amino acid identity and 83% similarity to the yeast protein,
except in the N-terminus, and contains a conserved glutamic acid residue (Glu98)
that is essential for H(+)-transporting activity. The gene for hATP6F (gene
symbol, ATP6F), which consists of eight exons and spans approximately 3.5 kb, was
isolated and mapped to human chromosome band 1p32.3 and the region 10.81 cR
centromeric of the STS marker SHGC36789 (LOD = 6.75) by fluorescence in situ
hybridization and radiation hybrid mapping, respectively. This is the first
evidence in human of the existence of a second gene encoding a distinct V-ATPase
proteolipid.
PMID- 9653650
TI - Long uninterrupted CGG repeats within the first exon of the human FMR1 gene are
not intrinsically unstable in transgenic mice.
AB - Despite the increasing number of disorders known to result from trinucleotide
repeat amplification, the molecular mechanism underlying these dynamic mutations
is still unknown. In an attempt to create a mouse model for the CGG repeat
instability seen in Fragile X syndrome, we constructed transgenes corresponding
to FMR1 premutation alleles. While in humans these alleles would expand to full
mutation with almost 100% certainty upon maternal transmission, they remain
stable in our transgenic mice. Therefore, the presence of a large number of
uninterrupted CGGs is not sufficient to cause instability in mice, even in the
context of flanking human FMR1 sequences.
PMID- 9653651
TI - cDNA cloning and characterization of a human proteasomal modulator subunit, p27
(PSMD9).
AB - We have employed cDNA cloning to deduce the complete primary structure of a new
subunit, designated p27, of the modulator trimer complex that stimulates the
association of the PA700 regulator with the catalytic 20S proteasome to form the
ATP-dependent active 26S proteasome. We found two distinct cDNAs encoding two
highly homologous proteins except in the C-terminal region, which are termed
tentatively p27-1 and p27-2. The short p27-2 cDNA has a deletion of 65 bp near
the 3'-end region of the long p27-1 cDNA, which encodes a large protein with an
extended C-terminal region, designated p27-L, whereas the long p27-1 cDNA encodes
a small protein named p27-S. The polypeptides of p27-L and p27-S consist of 223
and 209 amino acid residues with calculated molecular masses of 24,852 and 22,764
and isoelectric points of 6.50 and 5.28, respectively. Immunoblot analysis with
anti-p27 antibody revealed that p27, together with two other ATPase components,
TBP1 and p42, was associated with not only the modulator complex but also
significantly with the 26S proteasome complex, suggesting that the three are
common/sharing subunits in these two complexes. By the fluorescence in situ
hybridization method, the p27 (PSMD9) gene was mapped to the q24.2-q24.3 band of
human chromosome 12. Computer-assisted homology analysis revealed the high
sequence similarities of p27-L with a possible counterpart in Caenorhabditis
elegans and Saccharomyces cerevisiae whose function is yet unknown, the yeast
gene that is here termed NAS2 (non-ATPase subunit 2). Disruption of NAS2 had no
effect on cell viability, indicating that the subunit is not essential for
proliferation of yeast cells.
PMID- 9653652
TI - A putative human zinc-finger gene (ZFPL1) on 11q13, highly conserved in the mouse
and expressed in exocrine pancreas. The European Consortium on MEN 1.
AB - In the process of identification of the multiple endocrine neoplasia type 1 gene,
which was recently published, we isolated a novel gene in the 11q13 region. This
gene (named ZFPL1, for zinc-finger protein-like 1) is expressed strongly in the
exocrine pancreas as a 1.4-kb polyadenylated RNA encoding a putative protein of
310 amino acids. A mouse EST contig predicts an equally sized murine protein with
91% amino acid sequence identity to the human protein. No significant homology
with known proteins could be found through database screening. However, zinc
finger-like domains and leucine-zipper-like motifs in the predicted ZFPL1 protein
were identified, suggesting the presence of DNA-binding and dimerization domains
possibly involved in transcription regulation. This notion is supported by the
presence of a putative bipartite nuclear localization signal. This paper presents
the full-length cDNA sequence for this gene, its genomic structure and
chromosomal orientation, and expression studies by Northern blot hybridization
and RNA in situ hybridization.
PMID- 9653653
TI - Fine genetic and comparative mapping of the deafness mutation Ames waltzer on
mouse chromosome 10.
AB - The Ames waltzer (av) mouse mutant is an autosomal recessive deafness mutation on
mouse Chromosome 10. Previously, av had not been mapped relative to molecular
markers. We have performed an intersubspecific backcross with Mus musculus
castaneus and mapped microsatellite markers in this cross. Toothpick PCR on
previously frozen tissue samples from offspring was used as an efficient strategy
to screen a large number of animals quickly. In 1258 progeny tested we found
three recombinants for each of the flanking markers D10Mit199 and D10Mit64. In
addition, nine different genes (Ank3, Bcr, Gnaz, Tfam, Mif, Mmp11, Dcoh, Pyp, and
Gstt2) were mapped and eliminated genetically as candidate genes for av. av had
been discussed as a potential mouse model for the human deafness loci Usher
syndrome type ID (USH1D) and DFNB12. Comparative mapping shows that av maps near
an evolutionary break point and makes it unlikely that those loci are human
homologues of av. A human homologue of av is predicted to lie either on 22q11.2
or on 10q21. The orientation of conserved linkage groups between these two human
chromosomal regions relative to mouse Chromosome 10 was determined.
PMID- 9653654
TI - Cloning and characterization of the full-length cDNA and genomic sequences
encoding murine acid ceramidase.
AB - The full-length cDNA and genomic sequences encoding murine acid ceramidase (AC;
E.C. 3.5.1.23) have been isolated and characterized. The 2176-bp cDNA was
approximately 80% identical to the human cDNA (Koch et al., 1996) and predicted a
394-amino-acid polypeptide that was approximately 90% identical to the human
protein. A fluorescence-based assay system was developed to determine AC
enzymatic activity, and transfection of COS-1 cells with the full-length mouse
cDNA led to increased AC activity, demonstrating its functionality. The murine AC
gene, which spanned approximately 38 kb, consisted of 14 exons separated by 13
introns. The exons ranged in size from 46 to 1038 bp and were flanked by
exon/intron junctions that adhered closely to known donor and acceptor splice
site consensus sequences. Exon 1 encoded the putative translation start site and
the signal peptide region, while exon 14 encoded the carboxy end of the AC
polypeptide and all of the 3' untranslated region. Sequence analysis of a 497-bp
region upstream from the first in-frame ATG revealed several features of a
housekeeping promoter, as well as several tissue-specific and/or hormone
inducible regulatory sites. Insertion of this sequence into a chloramphenicol
acyltransferase (CAT) expression vector led an approximately fivefold increase in
CAT activity after transfection into NIH3T3 cells. Northern blot analysis and
enzymatic assays also were carried out on various murine tissues to examine AC
expression. Of the tissues studied, the highest AC activity and mRNA levels were
found in the kidney, followed by the brain; almost no AC activity or mRNA was
found in the testis or skeletal muscle. These latter studies provided clear
evidence that despite the housekeeping function of AC, its expression was tissue
specific.
PMID- 9653655
TI - Cloning, expression pattern, and chromosomal assignment to 16q23 of the human
gamma-adaptin gene (ADTG).
AB - Adaptins are important components of clathrin-coated vesicles transporting ligand
receptor complexes from the plasma membrane or from the trans-Golgi network to
lysosomes. Adaptins, together with medium and small subunits, form a
heterotetrameric complex called an adaptor, whose role is to promote the
formation of clathrin-coated pits and vesicles. We present the cloning and
sequencing of the human gamma-adaptin cDNA (HGMW-approved symbol ADTG) consisting
of 3723 bp with an open reading frame capable of encoding a protein of 825 amino
acids, 98.9% identical to the mouse protein. Northern blot analysis of the mouse
and human gamma-adaptin genes revealed a ubiquitous and abundant expression,
except in human adult lung. Using a monochromosomal somatic cell hybrid panel and
fluorescence in situ hybridization, we mapped this gene to human chromosome
16q23, which is syntenic with mouse chromosome 8, band D. In addition, we
localized genes for two other components of the AP-1 adaptor, i.e., the medium
(AP47) and small (AP19) subunits, to chromosomes 19 and 7, respectively.
Expression analysis of these genes in human tissues revealed ubiquitously
expressed transcripts of approximately 2.5 and 1.5 kb, respectively.
PMID- 9653656
TI - Cloning genes encoding receptors related to chemoattractant receptors.
AB - We report the cloning of a novel human gene (GPR32) encoding a putative G-protein
coupled receptor (GPCR) of 356 amino acids and a related pseudogene psi GPR32.
The deduced amino acid sequence of GPR32 shares 35-39% identity with members of
the chemoattractant receptor family. psi GPR32 shares 93% nucleotide identity
with GPR32. We identified a mouse EST encoding a putative GPCR (GPR33) of 309
amino acids. The deduced amino acid sequence of GPR33 shares 30-35% identity with
members of the chemoattractant receptor family and 36% identity with the receptor
encoded by GPR32. The human orthologue of GPR33 contains a single basepair
substitution with respect to the mouse, resulting in the presence of an in-frame
stop codon within the predicted second intracellular loop, demonstrating that it
is a pseudogene. Through fluorescence in situ hybridization and physical mapping
of YACs, both GPR32 and psi GPR32 were mapped to chromosomal 19, region q13.3,
while psi GPR33 was mapped to chromosome 14q12.
PMID- 9653657
TI - Mutant rescue by BAC clone injection in zebrafish.
AB - Genes essential for vertebrate body plan specification, organ development, and
organ function are likely to be shared between mammals and zebrafish, but only in
zebrafish have large-scale, genome-wide mutagenesis screens been conducted to
isolate embryonic lethal mutations. Discovering the roles played by these
disrupted genes requires their molecular characterization, which would be
facilitated by assaying large cloned genomic DNAs for their potential to rescue
mutant phenotypes. Here we demonstrate that bacterial artificial chromosomes can
rescue the phenotype of floating head (flh) mutants. Homozygous flh embryos lack
a differentiated notochord and have a reduced, discontinuous floor plate. Mutant
embryos injected with genomic clones containing the flh+ gene often had stretches
of several to many notochord cells overlaid by a row of floor-plate cells. In
contrast, control mutant embryos injected with artificial chromosomes lacking the
flh+ gene failed to form notochord. We conclude that the injection of large
insert genomic clones will speed the isolation of zebrafish genes disrupted by
mutation and hence the identification of gene functions necessary for development
of vertebrate embryos.
PMID- 9653659
TI - Distribution of transcription factor binding sites in the yeast genome suggests
abundance of coordinately regulated genes.
PMID- 9653658
TI - A gene for recessive nonsyndromic sensorineural deafness (DFNB18) maps to the
chromosomal region 11p14-p15.1 containing the Usher syndrome type 1C gene.
AB - Autosomal recessive nonsyndromic sensorineural deafness segregating in a large
consanguineous Indian family was mapped to chromosome 11p14-p15.1 defining a new
locus, DFNB18. A maximum lod score of 4.4 at theta = 0 was obtained for the
polymorphic micro-satellite marker D11S1888. Haplotype analysis localizes this
gene between markers D11S1307 and D11S2368, which is approximately 1.6 cM and
encompasses the region of Usher syndrome type 1C (USH1C). We postulate that
DFNB18 and USH1C are allelic variants of the same gene.
PMID- 9653660
TI - Mapping of two mouse membrane-type matrix metalloproteinase (MT-MMP) genes, Mmp15
and Mmp16, to mouse chromosomes 8 and 4, respectively.
PMID- 9653661
TI - B-cell activation in vitro by helper T cells specific to a protein region that is
recognized both by T cells and by antibodies.
AB - This laboratory had previously mapped the regions of T and B cell recognition on
sperm whale myoglobin (Mb). Mb has five regions (E1-E5) that are recognized by
both T cells and B cells (i.e. antibodies, Abs) and an additional region (E6)
that is recognized exclusively by T cells (i.e., TE6) and to which no Abs are
detectable. The responses to the site are each under separate genetic control.
Recently, we showed in an H-2d haplotype that TE6 cells preferentially activated
Mb-primed B cells (BMb) that made Abs against sites within E3 and E4 on the same
protein. In the present work, we established, from Mb-primed SJL mice, an E4
specific T cell line (TE4) by passage in vitro with synthetic peptide E4. At
relatively low numbers, these T cells activated syngeneic BMb cells in vitro to
produce anti-Mb Abs that recognized each of the antigenic sites within regions
E1, E2, E3, E4 and E5. We confirmed the ability of TE4 to activate B cells that
produce Abs against each of these regions by allowing TE4 to activate in vitro
syngeneic B cells that had been primed with E1, E2, E3, E4 or E5. The helper
activity of TE4 cells was dependent on the in vitro concentration of the
challenge Ag (intact Mb or peptide E4). Thus, T cells against an epitope may
provide help restricted to B cells that make Abs against selected antigenic sites
or they may activate B cells that make Abs against all the antigenic sites of a
protein. This might depend on the site-specificity of the T cell and/or on the
host.
PMID- 9653662
TI - Petechial hemorrhages in the small intestinal Peyer's patches: a new
manifestation of systemic anaphylaxis.
AB - Systemic anaphylaxis in the rat has major manifestations in the small intestine.
In August rats, but not in other strains, intestinal anaphylaxis was accompanied
by petechial hemorrhages in Peyer's patches. The occurrence of petechiae was not
proportional to the intensity of prostration, cyanosis or gut congestion. No
hemorrhages were found in other organs. The petechiae occurred in August rats of
either sex after sensitization and challenge with any of several antigens and
adjuvants and after passive sensitization with antiserum. The number of Peyer's
patches with hemorrhage varied from one to all 20 in individual rats. The
occurrence of petechiae was not influenced significantly by the route of
sensitization or challenge, by the presence or absence of pinworms in the cecum,
or by ancillary treatment at time of challenge with normal serum, normal blood,
heparin, pertussis vaccine or lipopolysaccharide. The intestinal mast cells of
the susceptible August rats were not different from the mast cells of the
resistant strains. Furthermore, mast cells did not reside in the lymphoid
follicles of Peyer's patches which was the site of the petechial hemorrhages in
anaphylactic August rats. Nor did injections of histamine, serotonin or both
cause hemorrhages in Peyer's patches.
PMID- 9653663
TI - Two novel screening methods for selecting monoclonal antibodies which
specifically inhibit DNase I enzyme activity.
AB - Two novel screening methods, single radial enzyme diffusion and the DNA-cast
polyacrylamide gel electrophoresis, for selecting monoclonal antibodies which
detect human deoxyribonuclease I (DNase I) enzyme activity are described. The
former was adopted for initial screening to select potential objective antibodies
from numerous hybridoma culture supernatants, because it was easy to perform and
a powerful mass-screening tool. The latter was utilized for the subsequent
precise selection of the antibodies in the supernatants selected after
preliminary screening by the former, because it was clearly more accurate and
sensitive, although the procedure was slightly more complicated. The consecutive
use of these two methods resulted in the isolation of 25 anti-human DNase I
antibodies, all of which specifically inhibited the activity of human DNase I.
PMID- 9653664
TI - Age-related changes in primary and secondary immune organs of the mouse.
AB - The present work describes the murine immune tissue evolution with age with
special emphasis on the bone marrow. To that effect we monitored the weights of
the thymus, spleen and axillary lymph nodes over the first year of life in
C57BL/6 male and female mice. In addition, we monitored the relative proportions
of erythroid, lymphoid and myeloid cells in the bone marrow, and performed in
vitro migration assays of bone marrow cells to thymic supernatants, with the aim
of determining whether the migration of such cells or the thymic attractive
capacity are affected by age. Before puberty, a remarkable decline in the
relative weight of the thymus, spleen and lymph nodes was observed; after that
stage, however, only the thymus showed an involution. The proportion of myeloid
cells in the bone marrow showed an increase with age. Furthermore, the migration
of myeloid cells to thymic supernatants increased with age and paralleled the
time-course of the myeloid cell increase found in the bone marrow. More
interestingly, the proportion of lymphoid cells to total bone marrow cells showed
a clear decline with age. The time-course of this decline closely paralleled that
of thymus weight, suggesting that the involution of the thymus may be related to
changes in the cell composition of the bone marrow.
PMID- 9653665
TI - Secretory component production by polarized epithelial cells from the human
female reproductive tract.
AB - At mucosal surfaces, the polymeric Ig receptor (pIgR) is responsible for
transporting polymeric IgA across epithelial cells. The purpose of this study was
to determine whether normal epithelial cells from the female reproductive tract
form tight junctions and produce secretory component, the external domain of the
pIgR. Uterine, cervical and vaginal tissues from women at different stages of the
menstrual cycle and following menopause were used to prepare purified epithelial
cell sheets, which were cultured in cell chambers. Transepithelial resistance was
measured and the media from apical and basolateral compartments assayed for
secretory component. Secretory component produced by uterine epithelial cells
accumulated preferentially in apical compartment and correlated with increased
transepithelial resistance. Seeding as epithelial sheets at 1 x 10(6) cells/cm2
of matrix coated cell chambers was required for growth. Epithelial cells from
endo-cervix and ecto-cervix, but not the vagina, also showed preferential
production and release of secretory component into the apical chamber. In
conclusion, normal epithelial cells from the human female reproductive tract grow
to confluence, become polarized and produce secretory component. Our results
suggest that uterine and cervical epithelial cells play a key regulatory role in
the control of IgA transcytosis from tissue into secretions.
PMID- 9653666
TI - Administration of silica sensitizes lipopolysaccharide responsiveness of murine
macrophages but inhibits T and B cell priming by inhibition of antigen presenting
function.
AB - Macrophages play a key role in natural host defense against infection by a
variety of pathogens. In addition, macrophages initiate the development of
acquired immunity via antigen processing and presentation. The role of
macrophages in resistance to pathogens, the development of autoimmune diseases
and the induction of acquired immunity has been studied by treatment of rodents
with reagents which are cytotoxic. We have studied the effects of one such
reagent, silica, on the function of spleen macrophages and peritoneal exudate
cells (PEC). Intraperitoneal administration of silica caused the accumulation of
spleen macrophages and neutrophils, reduction in the number of B cells and had a
modest effect on T cell abundance. The percentage of CD11b+ PEC was not affected
by silica treatment but total PEC recovery was diminished 5-8 fold. Silica
treatment did not cause release of TNF-alpha or IL-1-beta but, when stimulated
with lipopolysaccharide (LPS) in vitro after silica treatment, PEC or spleen
macrophages produced elevated levels of both cytokines compared to controls. In
contrast, release of IL-12 from non-LPS treated PEC was stimulated 4-5 fold by
silica treatment. In addition, sensitivity to LPS toxicity in vivo was
significantly enhanced by silica. The ability of macrophages to present antigen
to a T cell clone in vitro was found to be dramatically inhibited by silica
treatment, as was the ability to prime antigen-specific T cells and B cells by
antigen injection. Collectively these data demonstrate that silica treatment
enhances macrophage sensitivity to LPS exposure but inhibits antigen processing
and presentation.
PMID- 9653667
TI - Stress, neuropsychiatric disorders and immunological effects exerted by
benzodiazepines.
AB - Psychoneuroimmunology is a growing scientific field which deals with the mutual
interplay between nervous and immune systems. In this framework, many data have
demonstrated that cytokines (CKs) derived from the periphery are able to cross
the blood brain barrier and act upon the central nervous system (CNS) [e.g., the
hypothalamic-pituitary-adrenal axis (HPAA)], thus regulating several
physiological functions (thermoregulation, sleep, appetite) or damaging the
nervous tissue, when released in exaggerated amounts. On the other hand, nervous
cells, such as astrocytes and microglial cells also generate proinflammatory CKs
which may be detrimental for the CNS. The neuromodulating CK network can be
triggered by microorganisms and/or their products (i.e. bacterial endotoxins),
but also stressful life events may activate the HPAA, thus affecting the immune
system function. This review will place emphasis on some clinical conditions,
such as phobia and migraine without aura (MWA), characterized by anxiety
disorders. Patients affected by these neuropsychiatric alterations exhibit
multiple functional deficits of phagocytes and T lymphocytes which allow
penetration of various pathogens into the host. This is also supported by the
detection of circulating bacterial endotoxins and the evidence of both
spontaneous and induced exaggerated release of proinflammatory CKs in phobic and
MWA patients. The possible iatrogenic effects of benzodiazepines (BDZ) on the
immune system have been evaluated by in vitro and in vivo studies. In this
respect, it emerges that diazepam exerts an inhibitory function on the immune
system, while alprazolam behaves as an immunoenhancer. The presence of central
and/or peripheral BDZ receptors on immune cells seems to be the key mechanism
responsible for the immunomodulation exerted by these drugs.
PMID- 9653668
TI - The plasma FK506-binding protein 12 level is related to acute cellular rejection
in small bowel transplantation.
AB - Since FK506 binding protein (FKBP12) inhibits dose-dependently the
immunosuppressive activity of FK506 in vitro, plasma FKBP12 levels were measured
after rat small bowel transplantation (SBTx). The mean plasma FKBP12 level in
untreated recipients increased significantly at the onset of acute cellular
rejection (ACR) compared to that in FK506-treated recipients without rejection at
the same time after SBTx (P < 0.05). In both groups, however, the mean plasma
FKBP12 level did not increase at 1 day after SBTx. These results suggest that
plasma FKBP levels may be affected by ACR, but not by ischemia-reperfusion
injury. Therefore, the plasma FKBP12 level should be considered as one of the
parameters related to the immunosuppressive activity of FK506 in SBTx.
PMID- 9653669
TI - Effect of endotoxin on cytokine production and cell dynamics in mice.
AB - Previous studies have shown that endotoxin potentiates immune responses by direct
stimulation of B cells and macrophages. In the present study, we assessed the
ability of endotoxin to stimulate cells from different lymphoid tissue
compartments to release cytokines. The in vitro stimulation of macrophages with
endotoxin resulted in the production of IL-1 and TNF-alpha in a dose and time
dependent manner. Endotoxin also induced the production of IL-2, IFN-gamma and IL
4 secretion in a dose dependent manner in cultured spleen, mesenteric lymph nodes
and Peyer's patches cells. The intraperitoneal administration of endotoxin in
mice resulted in the accumulation of leucocytes in the peritoneal cavity and in
the increase of IL-1, IL-6, TNF-alpha and IFN-gamma concentration in serum. In
conclusion, this study confirmed that endotoxin possesses immunomodulatory
activities capable of stimulating immune functions both in vitro and in vivo.
PMID- 9653670
TI - In-line affinity chromatographic removal of specific antibody from rabbits with
experimental myasthenia gravis as a prelude to immunotherapy.
AB - Myasthenia gravis is an autoimmune disease in which antibodies are produced
against one's acetylcholine receptors, resulting in complement-mediated membrane
destruction and internalization of antibody-receptor complexes. Symptoms range
from weakening of extraocular muscles to severe impairment of movement and
breathing. Prior to administering a therapeutic agent to eliminate antibody
producing lymphocytes, it will be necessary to remove specific antibody from the
circulation. This process was investigated in an animal model of ex vivo specific
immunoadsorption using awake, conscious rabbits. Following arterial blood
separation, plasma was pumped upward through an affinity column containing
covalently-bound acetylcholine receptor. Treated plasma was returned to the
rabbit. Within a one-hour ex vivo procedure, specific antibody levels could be
lowered from 16.2 ng/ml to less than 0.6 ng/ml, a reduction of more than 95%. By
washing the column, at least four exchanges could be performed before specific
antibody removal significantly diminished. The effects of specific antibody
removal upon muscle function varied among individual rabbits, but if symptoms
were not severe following passive transfer of purified monoclonal antibody to
induce myasthenia, removal of 60% of the total specific antibody resulted in
clinical improvement, as monitored by an animal's response to gallamine
triethiodide.
PMID- 9653671
TI - Modulation of cytoskeleton assembly capacity and oxidative response in aged
neutrophils.
AB - Several reports have emphasized that aged polymorphonuclear cells (PMN) exhibit
an impairment of superoxide anion (O2-) generation when triggered with formyl
methionyl-leucine-phenylalanine (FMLP) in comparison to the younger counterpart.
Since microfilaments and microtubules are involved in PMN-mediated functions, in
a group of old donors we assessed the effects of either actin stabilizing and
disrupting agents, i.e. phalloidin and cytochalasin B, or microtubule
stabilization or disruption by taxol and colchicine, respectively, on FMLP
triggered neutrophil oxidative responsiveness. Results show that phalloidin
treatment, at a concentration ranging from 10(-6) to 10(-8) M, gave rise to an
inhibition of O2- release by aged PMN, while the same effect was seen in
similarly treated young cells at a concentration of 10(-7) M only. On the
contrary, cytochalasin B pretreatment led to an enhancement of O2- generation in
both young and aged neutrophils, even if to a lower extent in the latter group.
At the same time, taxol at 10(-8) M strength inhibited young cell responsiveness,
while no effects were induced by colchicine treatment. Quite interestingly,
elderly neutrophil function was negatively modulated by both microtubule
affecting compounds. Altogether, these findings suggest the possible relevance of
cytoskeletal affecting compounds in the modulation of FMLP-stimulated O2- release
during senescence.
PMID- 9653672
TI - In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine "sho
seiryu-to"--stimulation of mucosal immune system and effect on allergic pulmonary
inflammation model mice.
AB - When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu
to (SST)" (1 g/kg, 10 times) orally from 7 days before to 5 days after the
infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal-site
restricted infection, SST caused increment of the influenza virus hemagglutinin
specific IgA antibody secreting cells in nasal lymphocyte but not in Peyer's
patch lymphocyte at 6 days after infection in comparison with water-treated mice.
Oral administration of SST also augmented IL-2 receptor beta chain+ (activated) T
cell in Peyer's patch lymphocyte, but not in the nasal lymphocyte. We previously
reported that SST showed potent anti-influenza virus activity through
augmentation of the antiviral IgA antibody titer in the nasal and broncho
alveolar cavities of the mice (T. Nagai and H. Yamada, 1994, Int. J.
Immunopharmacol. 16, 605-613). These results suggest that oral administration of
SST shows anti-influenza virus activity in the nasal cavity by activation of T
cell in Peyer's patch lymphocyte and stimulation of production of anti-influenza
virus IgA antibody in nasal lymphocyte. When ovalbumin-sensitized allergic
pulmonary inflammation model mice were administered orally with SST (1 g/kg) from
8 days before (11 times) or from 2 h after (4 times) to 4 days after the
infection and infected with mouse-adapted influenza virus A/PR/8/34, replications
of the virus in the both nasal and broncho-alveolar cavities or only nasal cavity
were significantly inhibited at 5 days after infection in comparison with water
treated control by augmenting antiviral IgA antibody, respectively. These results
suggest that SST is useful for both prophylaxis and treatment of influenza virus
infection on patients with allergic pulmonary inflammation, such as bronchial
asthma.
PMID- 9653673
TI - Taraxacum officinale restores inhibition of nitric oxide production by cadmium in
mouse peritoneal macrophages.
AB - Nitric oxide (NO) produced at high concentrations by the inducible NO synthase is
an important effector molecule involved in immune regulation and defense. The
involvement of NO in the toxicity of cadmium (Cd) has been proposed. We have
established that Cd inhibits the production of NO by recombinant IFN-gamma (rIFN
gamma) and lipopolysaccharide-stimulated mouse peritoneal macrophages. In the
present study, we searched restoration drug against the inhibition of NO
production by Cd in Oriental medicine. An aqueous extract of Taraxacum officinale
(Compositae) (TOAE) restored the inhibition of NO production by mouse peritoneal
macrophages pretreated with Cd in a dose-dependent manner. The effect of TOAE was
mainly dependent on TOAE-induced tumor necrosis factor-alpha (TNF-alpha)
secretion. These results suggest that the capacity of TOAE to restore NO
production from interferon-gamma (IFN-gamma)-primed mouse peritoneal macrophages
is the result of TOAE-induced TNF-alpha secretion.
PMID- 9653674
TI - Alterations in immune parameters associated with low level methylmercury exposure
in mice.
AB - Methylmercury (MeHg) is a known toxicant and continues to be a significant
environmental contaminant. While the neurotoxicity and developmental toxicity of
MeHg are well established, the immunotoxic effects of MeHg are just now being
studied and described. This study evaluated strain and gender specific effects of
low level, prolonged MeHg exposure in mice. Mice were exposed to MeHg in the
drinking water (0, 3 or 10 ppm) for 4 weeks. Splenocytes and thymocytes were
evaluated for alterations in immunophenotype, GSH levels, and intracellular Ca2+
flux after mitogen stimulation. MeHg exposure resulted in alterations in
splenocyte and thymocyte subsets and a dose dependent decrease in GSH levels (as
measured by monochlorobimane fluorescence and flow cytometry) of all splenocyte
subsets. This decrease in GSH was further confirmed by biochemical assay in
splenocytes. In addition, there was a dose response related decrease in mitogen
stimulated Ca2+ flux and in the percentages of CD4+ splenocytes and CD8+
splenocytes from mice exposed to 10 ppm of MeHg. These results suggest that low
level chronic MeHg exposure may cause immune disfunction by disturbing thiol
redox balance, transmembrane signaling and splenic cellularity.
PMID- 9653675
TI - Effects of low doses of oestradiol, testosterone and dihydrotestosterone on the
immune response of broiler chicks.
AB - Administration of either 1 microgram kg-1 BW oestradiol 17 beta (E2), 0.1 mg kg-1
BW testosterone (T) or 0.2 mg kg-1 BW dihydrotestosterone (DHT) in feed to
broiler chicks for 50 days caused increased serum concentration of the hormones
compared to the control birds that were given no drugs. E2 and T but not DHT
resulted in a significant decrease of the total number of leukocytes, lymphocytes
and the weight of bursa of Fabricious. The hormones significantly reduced the
macrophage phagocytic activity compared to controls. It is suggested that
prolonged administration of low doses of E2 and T but not DHT to chicken may
induce immunosuppressant effect.
PMID- 9653676
TI - Diesel exhaust particles enhance airway responsiveness following allergen
exposure in mice.
AB - We have previously reported that intratracheal instillation of diesel exhaust
particles (DEP) enhances allergen-induced eosinophilic airway inflammation, local
expression of interleukin-5 and granulocyte macrophage-colony stimulating factor,
and allergen-specific production of IgE and IgG in mice. The present study was
undertaken to elucidate the effects of DEP on airway hyperresponsiveness as
another characteristic feature of allergic asthma. The animals were randomized
into four experimental groups that received intratracheal instillation with
vehicle, ovalbumin (OVA), DEP, or the combination of OVA and DEP on a weekly
basis for 6 weeks. Respiratory resistance (Rrs) was measured 24 h after the last
instillation. An increase in Rrs in animals that inhaled acetylcholine was
significantly greater in the combined treatment with OVA and DEP than in the
other treatments. The present study indicates that DEP can enhance airway
responsiveness associated with allergen exposure, and provides experimental
evidence that DEP may deteriorate the pathophysiology of allergen-related
respiratory disease such as allergic asthma.
PMID- 9653677
TI - The utility of the Fear Survey Schedule-III: an extended replication.
AB - This investigation examined the factor structure of the Fear Survey Schedule-III
in patients with specific anxiety disorders, including patients with panic
disorder, agoraphobia without panic, generalized anxiety disorder, social phobia,
specific phobia, obsessive compulsive disorder, post traumatic stress disorder,
and anxiety disorder NOS. Four factors were obtained, reflecting a similar
structure as has been noted in other studies. However, the ability of the
obtained factors to discriminate among patients with panic disorder, social
phobia, and specific phobia was not high. Future directions are highlighted.
PMID- 9653678
TI - Social anxiety and peer relations among adolescents: testing a psychobiological
model.
AB - This study tested hypotheses derived from Trower and Gilbert's (1989) model of
social anxiety. Participants were 1,179 students (594 males and 585 females) in
grades 6, 7, 8, 9, and 11. Participants completed the Social Anxiety Scale for
Adolescents and a sociometric nomination task. Nominations from the following
behavioral descriptors: most cooperative, class leader, fights the most, and
easiest to push around, were used to classify students into four peer nomination
groups (i.e., cooperative, friendly dominant, hostile dominant, and submissive).
Results indicated that students classified as submissive reported greater social
anxiety than those classified as cooperative, friendly dominant, and hostile
dominant. Implications of these results for further study of the Trower and
Gilbert (1989) model of social anxiety are discussed.
PMID- 9653679
TI - Crime-related trauma: psychological distress in victims of bankrobbery.
AB - This study examines the relationship between the experience of a traumatic event,
that is, a bankrobbery, and its psychological consequences. Two groups of
employees of a major commercial bank in the Netherlands participated in this
study. One group (n = 310) consisted of subjects who had experienced a
bankrobbery and worked in high-frequency bankrobbery areas; the other matched
control group (n = 214) consisted of nonrobbed employees from banks in the same
area. Victimized subjects displayed more signs of psychological distress than the
control subjects, but distress decreased over time. The main findings of this
study are that a depressive/avoidant coping style, strong threat perception
during the robbery, and additional life events were positively related to
posttraumatic distress as assessed by the Impact of Event Scale and the Symptom
Check List (SCL-90), and self-esteem was negatively associated with the SCL-90
only.
PMID- 9653680
TI - An investigation of gender differences in social phobia.
AB - The present study was an exploratory investigation of gender differences in a
large sample of persons with social phobia. Potential differences in demographic
characteristics, comorbidity, severity of fear, and situations feared were
examined. No differences were found on history of social phobia, social phobia
subtype, or comorbidity of additional anxiety disorders, mood disorders, or
avoidant personality disorder. However, women exhibited more severe social fears
as indexed by several assessment instruments. Some differences between men and
women also emerged in their report of severity of fear in specific situations.
Women reported significantly greater fear than men while talking to authority,
acting/performing/giving a talk in front of an audience, working while being
observed, entering a room when others are already seated, being the center of
attention, speaking up at a meeting, expressing disagreement or disapproval to
people they do not know very well, giving a report to a group, and giving a
party. Men reported significantly more fear than women regarding urinating in
public bathrooms and returning goods to a store. Additionally, there were some
differences in the proportion of men and women reporting fear in different
situations. Specifically, more women than men reported fear of going to a party,
and more men than women reported fear of urinating in a public restroom. Gender
differences among patients with social phobia are discussed in the context of
traditional sex-role expectations.
PMID- 9653681
TI - Additional findings on the association between anxiety sensitivity and
hypochondriacal concerns: examination of patients with major depression.
AB - Hypochondriacal concerns ranging from disease phobias to bodily preoccupations
are common among patients with panic disorder. In a previous study of patients
with panic disorder, we found that, of a number of symptom dimensions examined,
anxiety sensitivity was the strongest predictor of hypochondriacal concerns. This
finding has been the topic of subsequent debate in the anxiety literature, with
concerns raised whether true hypochondriacal concerns were confounded with
typical panic-related concerns. To clarify this issue, we now report on the
association between anxiety sensitivity and hypochondriacal concerns in 100
patients with major depression and no history of panic disorder. Consistent with
our previous study, we found that of the symptoms examined--anxiety sensitivity,
depressed mood, anxious mood, somatic symptoms, and anger/hostility--anxiety
sensitivity was the strongest predictor of hypochondriacal concerns. Findings are
discussed in relation to the role of catastrophic interpretations of somatic
symptoms in depression, panic disorder, and hypochondriasis.
PMID- 9653682
TI - Stressful life events and personality styles: relation to impairment and
treatment outcome in patients with social phobia.
AB - Forty-five patients with social phobia and 15 individuals with no mental disorder
were compared on number and type of life events experienced. Social phobia
patients were further examined to evaluate the effect of negative life events and
of the interaction between personality style and life events on severity of
impairment and reactions to cognitive-behavioral group therapy. Patients with
social phobia reported more negative life events than participants with no mental
disorder. Among patients with social phobia, more frequent negative life events
were associated with higher scores on measures of depression and general anxiety.
Patients high on autonomy who reported more negative autonomous (i.e.,
achievement-oriented) life events also scored higher on measures of social
anxiety and general anxiety. There were no significant interactions between
sociotropy and the frequency of reported socially oriented negative life events.
However, patients high on sociotropy scored higher on measures of social anxiety,
depression, and general anxiety. Patients who had experienced more negative life
events improved more after treatment on measures of social anxiety than did those
who had experienced fewer negative life events. Implications of these findings
and recommendations for future research are discussed.
PMID- 9653683
TI - Worry themes in primary GAD, secondary GAD, and other anxiety disorders.
AB - This study examines worry themes among 87 anxiety disorder patients divided into
three groups: (a) 24 primary generalized anxiety disorder (GAD) patients, (b) 25
secondary GAD patients, and (c) 38 other anxiety disorder patients (primarily
obsessive-compulsive disorder, social phobia and panic disorder with
agoraphobia). Structured and free-recall measures were used to measure five worry
themes: relationships, work, finances, physical threat, and the future. Both
types of measures revealed that GAD patients worry more about the future than non
GAD patients. Further, post hoc analyses testing for linear relationships
indicated that primary GAD patients worry more about the future than secondary
GAD patients who in turn worry more about the future than other anxiety disorder
patients. The results suggest that although worry about immediate problems may
not differentiate GAD patients from other anxiety disorder patients, high levels
of worry about future events may be a distinguishing feature of GAD.
PMID- 9653684
TI - Why do episodes of panic stop?
AB - Episodes of panic are self-limiting--they all come to an end. However, it has not
been explained how and why they end. Neither the cognitive nor the biological
theory of panic deals with this phenomenon. As a first step toward an
understanding of what stops a panic, we collected evidence about the self
limiting nature of these episodes. A semistructured interview was developed and
conducted with 25 participants who had received a diagnosis of panic disorder.
Participants reported a variety of triggers of panic, signs that a panic was
ending, and strategies used to terminate panic episodes. A substantial proportion
of participants indicated that there was a refractory period following panic
episodes. The theoretical and therapeutic significance of this self-limiting
feature of panic episodes is considered, as is the probable occurrence of a
postpanic refractory period.
PMID- 9653685
TI - The effect of joint mobilization as a component of comprehensive treatment for
primary shoulder impingement syndrome.
AB - Primary shoulder impingement syndrome is a common shoulder problem which, if
treated ineffectively, can lead to more serious pathology and expensive
treatment. This study examined whether subjects receiving joint mobilization and
comprehensive treatment (hot packs, active range of motion, physiologic
stretching, muscle strengthening, soft tissue mobilization, and patient
education) would have improved pain, mobility, and function compared with similar
patients receiving comprehensive treatment alone. Subjects were eight men and six
women (mean age = 52.9 years) with primary shoulder impingement syndrome
(superolateral shoulder pain, decreased active humeral elevation, limited
overhead function). Following random assignment to experimental (N = 7) and
control groups (N = 7), three blinded evaluators tested 24-hour pain (visual
analog scale), pain with subacromial compression test (visual analog scale),
active range of motion (goniometry), and function (reaching forward, behind the
head, and across the body in an overhead position) before and after nine
treatments. One-tailed analyses of covariance (baseline values as covariates)
showed that the experimental group had less 24-hour pain and pain with
subacromial compression test but no differences in range of motion and function
(Mann-Whitney U) compared with controls. The experimental group improved on all
variables, while the control group improved only on mobility and function (one
tailed, paired t tests; Wilcoxon matched pairs). Age, side of dominance, duration
of symptoms, treatment attendance, exercise quality, and adherence had no effect
on the outcomes. Results may be affected by inadequate sample size, minimal
capsular tightness, insensitive functional scale, nonspecific motion
measurements, position at which mobilization treatment was given, or a strong
effect of comprehensive treatment. Mobilization decreased 24-hour pain and pain
with subacromial compression test in patients with primary shoulder impingement
syndrome, but larger replication studies are needed to assess more clearly
mobilization's influence on motion and function.
PMID- 9653686
TI - Comparison of 6- and 7-day physical therapy coverage on length of stay and
discharge outcome for individuals with total hip and knee arthroplasty.
AB - Providing physical therapy service on Sundays is a much debated topic among
hospital administrators. The purpose of this study was to determine if 7 days per
week of physical therapy coverage results in shorter lengths of stay and
differing discharge status than 6 days per week. A total of 140 subjects with hip
or knee arthroplasty participated; there were 80 in the 6-day groups and 60 in
the 7-day groups. Data on postoperative length of stay, discharge destination,
and discharge disposition were collected by retrospective medical record review.
The Mann-Whitney U test was used to test for differences in length of stay data,
and the chi-squared test was used to test for differences in discharge
disposition and discharge destination. No significant differences in
postoperative length of stay, discharge destination, nor discharge disposition
existed between the 6- and 7-day physical therapy coverage hip or knee
arthroplasty groups. However, the power of the statistical tests applied was low.
This study provides no evidence that 7-day per week physical therapy results in
shortened postoperative length of stay, differing discharge destination, nor
differing discharge disposition for patients undergoing hip or knee arthroplasty.
PMID- 9653687
TI - The relationship between isokinetic quadriceps strength test and hop tests for
distance and one-legged vertical jump test following anterior cruciate ligament
reconstruction.
AB - Isokinetic measurements and functional tests are often used to assess function
following knee ligament reconstruction using the opposite limb as a control.
However, the question of whether the uninvolved leg may serve as a reference on
functional tests has not been adequately answered. In particular, the one-legged
rebound vertical jump has not been used to assess functional levels following
surgery of the cruciate ligament. The purposes of this study were: 1) to
determine whether the uninvolved leg is within normal range of an age- and weight
matched group, 2) to determine differences between the involved and uninvolved
leg in patients after anterior cruciate ligament reconstruction, 3) to examine
the relationship between knee extensor strength and four functional performance
tests, and 4) to determine if the one-legged rebound vertical jump yields more
information in the assessment of knee function than the other functional tests
with respect to two time-frames. Fifty healthy subjects (group A, mean age = 28.1
years) and 55 anterior cruciate ligament patients (groups B and C) participated
in dynamometric measurement, one-legged and two-legged vertical jump, and the
single- and the triple-hop test. Mean time for testing was 13 weeks following
surgery for group B (N = 30, mean age = 27.8 years) and 54 weeks following
surgery for group C (N = 25, mean age = 29.9 years). Pearson product moment
correlation coefficients between peak torque and single and triple hop were r =
.45, r = .48, r = .51, and r = .55 for groups B and C, respectively. Pearson
product moment correlation coefficients between peak torque and the height of the
vertical jump was r = .51 for group C. Results for group A revealed limb symmetry
indices of 95% or more on all functional performance and isokinetic tests. In
group B, all patients showed a limb symmetry index of less than 85% on all tests.
In group C, the index for the vertical jump was the only functional test that
fell below the level of 85%. Regardless of whether the dominant or nondominant
leg is involved, the uninvolved leg can be used adequately as a reference guide
for outcome from rehabilitation using these measurements. The one-legged vertical
jump test is capable of detecting functional limitations of the lower limb
following knee ligament reconstruction up to 54 weeks postoperatively.
PMID- 9653688
TI - Knee joint accessory motion following anterior cruciate ligament allograft
reconstruction: a preliminary report.
AB - Early in the postoperative period, changes in tibial translation have been noted
in patient populations following anterior cruciate ligament reconstructive
surgery. Deformation due to a lengthening of the ligament graft has been the most
widely accepted reason for the change in tibial translation. Treatment techniques
have not been proven successful in the abatement or reversal of this graft
lengthening. The purpose of this study was to investigate the effect of
functional bracing on tibial translation during the first year postoperatively in
a group of patients with early changes in tibial translation. Three consecutive
patients with early increases in KT-2000 manual maximum total drawer following
bone-patellar tendon-bone allograft reconstruction were identified as subjects in
the control group. Five consecutive anterior cruciate ligament bone-patellar
tendon-bone allografts with early increases in KT-2000 manual maximum total
drawer were identified as subjects in the treatment group. These patients were
followed monthly during the first year postoperatively by manual maximum total
drawer KT-2000 testing. Criteria for inclusion in the treatment and control
groups included KT-2000 testing, with an increase in translation of greater than
or equal to 2 mm when compared with the uninvolved knee during the first year
postoperatively. The treatment group was required to wear a functional knee brace
during all weight-bearing activities until KT-2000 displacement measures were
stabilized for 3 consecutive months. Treatment with the functional brace resulted
in a mean 2.3-mm decrease in tibial translation in the manual maximum total
drawer KT-2000 when comparing the involved and uninvolved knee prebracing with
posttreatment. All five subjects in the treatment group had a decrease in tibial
translation. A Median Test comparing the control and treatment group's KT-2000
scores was significant at the p < .05 level. Patients who experience early
increases in tibial translation with anterior cruciate ligament reconstructions
may be assisted in a reduction of the displacement by the use of a functional
brace.
PMID- 9653689
TI - Quantification of elastic resistance knee rehabilitation exercises.
AB - Elastic resistance exercises are frequently used for knee rehabilitation
following injury and/or surgery. The evidence supporting this mode of
rehabilitation is primarily anecdotal, and no biomechanical assessment of elastic
resistance exercises has been previously published. The purpose of this project
was to quantify muscle activation levels, knee joint angles, and applied force
during five rehabilitation exercises utilizing an elastic resistance device.
Twelve subjects with no previous knee injury performed double knee dip, hamstring
pull, leg press, single knee dip, and side-to-side jump exercises while sagittal
plane kinematics, applied force from the elastic resistance device, and
electromyographic activity of eight lower extremity muscles were collected. The
muscle activation patterns suggest a progressive continuum of rehabilitation
exercises that can be applied to nonoperative injuries as well as anterior
cruciate ligament reconstructions.
PMID- 9653691
TI - Treatment of sexually transmitted diseases. 1998 recommendations by the Centers
for Disease Control and Prevention.
PMID- 9653690
TI - Hip biomechanics during gait.
AB - The literature is devoid of complete descriptions of hip biomechanics during
gait. We present for the first time simultaneously acquired in vivo acetabular
contact pressures, ground reaction forces, kinematics, hip torques, and
electromyographic (EMG) activity during gait with and without a cane from an 85
year-old male with a left instrumented femoral head prosthesis. Highest
acetabular contact pressures occurred in all gait trials at the posterosuperior
acetabulum, just prior to peak EMG, adductor torque, and ground reaction force
during late stance phase. Contralateral cane use reduced both peak acetabular
contact pressure and gluteus medius EMG but not adductor torque or ground
reaction force. These data identify a small area of high acetabular and femoral
head stress that could occur during each of a human's millions of gait cycles
annually and indicate that muscle activity, rather than solely body weight,
drives hip loading, Clinicians who desire to limit hip loads should reduce both
hip muscle contraction and weight bearing in late stance.
PMID- 9653692
TI - Genuine stress urinary incontinence in women. New laparoscopic paravaginal
reconstruction.
AB - OBJECTIVE: To assess a new laparoscopic technique of paravaginal repair, adapted
from a classic laparotomy procedure, for genuine stress urinary incontinence.
STUDY DESIGN: From January 1992 to July 1997, 28 patients in a consecutive,
prospective clinical case study were subjected to laparoscopic paravaginal
repair. No concomitant surgery was performed. A clinical diagnosis of genuine
stress urinary incontinence was documented by cystometry following a positive
cough stress test. When indicated, a multichannel urodynamics study was
performed. RESULTS: In 16 patients (57%) of 28, the right pelvic side was
affected, and in 43% fascia damage was identified and repaired bilaterally. The
average operative time was 2 hours, 45 minutes; average blood loss was 1.2 g
hemoglobin. No intraoperative, immediate postoperative, delayed postoperative or
anesthesia-associated complications were observed. Patients were discharged from
the surgical units in an average of 5 hours, 15 minutes. There was no
postoperative hospital readmission. CONCLUSION: Laparoscopic paravaginal repair
is simple and safe and has a 93% cure rate. It is an attractive alternative to
laparotomy.
PMID- 9653693
TI - Myomectomy performed concurrently with tuboplasty.
AB - OBJECTIVE: To determine whether women who require tuboplasty for infertility and
have associated uterine leiomyomas that require removal should have the
myomectomy done concurrently. STUDY DESIGN: Eighty-nine infertility patients
underwent tuboplasty alone for proximal tubal obstruction, 30 others were treated
by both myomectomy and tuboplasty during the same operation, and 15 others
underwent tuboplasty, leaving the myomas in situ. The tuboplasty in all cases
consisted of tubal resection and anastomosis (TRA). The pregnancy rates and
outcomes in the three groups were compared. RESULTS: Of the 89 patients who
underwent TRA alone, 74.2% (66 patients) became pregnant, and of those 66, 15.2%
had a spontaneous miscarriage, 24.2% developed an ectopic pregnancy, and 60.6%
achieved a viable birth. By comparison, of 30 patients who had both TRA and
myomectomy, 63.6% (19 patients) conceived, and of those 19, 15.8% miscarried,
26.3% developed ectopic pregnancies, and 57.9% achieved viable births. Of 15
patients who underwent TRA leaving the myomas in situ, 73% (11) became pregnant,
and of those 11, 45% (5) miscarried, 18% (2) had ectopic pregnancies and 36% (4)
gave birth to viable infants. The incidence of pregnancies, ectopic gestations,
miscarriages and viable births in the three groups showed no statistical
differences. CONCLUSION: When myomectomy is indicated, because of the lack of
disadvantages of performing it at the time of tuboplasty, the combined surgical
approach should be the procedure of choice rather than leaving the myomas in situ
for their removal in a separate operation at a later date.
PMID- 9653694
TI - Fascia lata suburethral sling vs. Burch retropubic urethropexy. A comparison of
morbidity.
AB - OBJECTIVE: To compare morbidity from the fascia lata sling to that from the Burch
procedure. STUDY DESIGN: The charts of 64 consecutive patients undergoing the two
procedures were reviewed for perioperative, immediate postoperative and delayed
postoperative complications. RESULTS: Mean age was significantly older and prior
surgery more common in the sling group, but parity and weight were comparable for
the two groups. Operative time, estimated blood loss, change in hematocrit,
incidence of transfusion, use of narcotics and hospital stay were not
statistically different. Duration of catheter use was 2.2 days longer in the
sling group (8.96 vs. 6.75 days, P = .387). Comparison of the sling vs. Burch,
respectively, showed persistent urge incontinence in 42.8% and 40.0%, new urge
incontinence in 22.2% and 16.6%, and cystotomy in 11% and 0%. CONCLUSION: The
fascia lata sling procedure has morbidity comparable to that of Burch retropubic
urethropexy. Urge incontinence needs to be specifically addressed preoperatively
in both groups of patients.
PMID- 9653695
TI - Creighton Model NaProEducation Technology for avoiding pregnancy. Use
effectiveness.
AB - OBJECTIVE: To evaluate the use effectiveness of Creighton Model (CrM)
NaProEducation Technology for avoiding pregnancy. STUDY DESIGN: CrM is a medical
model of natural procreation education that is a fully standardized modification
of the Billings ovulation method. This system has been used as a means to avoid
pregnancy and has been prospectively evaluated in five use effectiveness studies.
A prospective life-table analysis of the five studies (meta-analysis) was
undertaken, yielding both net and gross rates. Discontinuation rates were also
calculated. These studies were conducted at CrM centers in Omaha, St. Louis,
Wichita, Houston, and Milwaukee. RESULTS: A total of 1,876 couples used CrM NET
for a total of 17,130.0 couple months of use. The method and use effectiveness
rates for avoiding pregnancy were 99.5 and 96.8 at the 12th ordinal month and
99.5 and 96.4 at the 18th ordinal month, respectively. The discontinuation rate
was 11.3% at the 12th ordinal month and 12.1% at the 18th ordinal month.
CONCLUSION: CrM is highly effective as a means of avoiding pregnancy in both its
method and use effectiveness. The method effectiveness has remained stable over
the years of the studies, but the use effectiveness for avoiding pregnancy
appears to have improved over the study period.
PMID- 9653696
TI - Sperm penetration assay in predicting successful in vitro fertilization. A meta
analysis.
AB - OBJECTIVE: To determine if the performance of the sperm penetration assay (SPA)
is useful in predicting successful in vitro fertilization (IVF). METHODS: A meta
analysis was set up to determine the performance of SPA in the prediction of IVF
success. We collected data on 647 patients in 24 studies. For each study, a two
by-two table was constructed from the results of SPA and IVF. RESULTS: The
sensitivity and specificity of SPA as compared to IVF were heterogeneous. A
summary receiver operating characteristics curve could be estimated, showing that
the sensitivity of SPA was only 37%, with a specificity of 95%. Subgroup analysis
did not explain the lack of homogeneity. CONCLUSION: Since withholding IVF
inappropriately has major consequences, performing SPA is insufficient for
selecting patients for treatment with IVF-embryo transfer.
PMID- 9653697
TI - Single-dose azithromycin for Chlamydia in pregnant women.
AB - OBJECTIVE: To assess the efficacy and occurrence of severe side effects
associated with the use of a single dose of azithromycin in the treatment of
Chlamydia trachomatis in pregnant women. STUDY DESIGN: Patients and their sexual
partners were randomized into three treatment groups: both the patient and her
sexual partner received a single dose of azithromycin (group 1); the patient was
given a standard course of erythromycin, while her partner was given a standard
course of tetracycline (group 2); and the patient was given a single dose of
azithromycin with the sexual partner given a standard course of tetracycline
(group 3). Group 3 was included in order to assess the relative efficacy of
tetracycline with respect to the use of azithromycin among patients and to
indirectly assess possible patient reinfection by sexual partners. RESULTS: With
respect to the cure rate, 4.5% of study participants given azithromycin has
positive cultures vs. 21.1% of patients given erythromycin or tetracycline (P =
.018). With respect to side effects severe enough to warrant a change in
medication, 7.4% of patients receiving azithromycin reported suffering such side
effects vs. 38.8% of patients given erythromycin (P = .02). Among sexual
partners, 28.6% given tetracycline reported severe side effects vs. none of those
given azithromycin (P = .03). CONCLUSION: Azithromycin in the treatment of C
trachomatis in pregnant women substantially improved the cure rates while
substantially reducing the occurrence of severe side effects associated with the
use of a standard course of erythromycin. Since both tetracycline and
erythromycin are known to be effective against C trachomatis infection, the
improved efficacy of azithromycin is probably due to noncompliance with the
multidose, multiday regimen associated with the use of these two antibiotics.
PMID- 9653698
TI - Ectopic pregnancy in sterilized and nonsterilized women. A comparison.
AB - OBJECTIVE: To assess whether differences occurred in the presentation, treatment
and postoperative outcomes of ectopic pregnancy in sterilized and nonsterilized
women. STUDY DESIGN: All cases of ectopic pregnancy admitted over five years at
two hospitals were reviewed. Using a case-control method, patients with ectopic
pregnancy and prior tubal sterilization were compared with the next nonsterilized
patient with ectopic pregnancy admitted within 30 days. Statistical comparison,
utilizing t tests, chi 2 tests of Fisher's exact test, when appropriate, was
performed. RESULTS: Thirty-eight (18%) of 208 patients with ectopics during the
study period had undergone prior sterilization. This group, when compared with
the 38 nonsterilized patients with ectopics, was similar for gestational age at
diagnosis, frequency of pelvic inflammatory and sexually transmitted diseases,
and mean human chorionic gonadotropin (hCG) level; the preoperative sonographic
findings were also similar in the two groups. Sterilized patients were less
likely than controls to have had serial hCG levels, while their mean duration of
symptoms at admission was shorter. Although both groups had a similar
distribution of surgical management (laparoscopy, laparotomy or both) and
postoperative complications, there were trends toward a higher risk of ectopic
rupture and hemoperitoneum in sterilized patients. CONCLUSION: Ectopic
pregnancies following tubal sterilization have clinical manifestations and
surgical outcomes similar to those occurring without prior sterilization, except
for less frequent determination of serial hCGs, probably related to a shorter
duration of reported preceding symptoms. The trend toward more frequent rupture
and hemoperitoneum in this group suggests that sterilized patients are less
likely to heed the early warnings of this complication.
PMID- 9653699
TI - Fetal congenital malformations. Biophysical profile evaluation.
AB - OBJECTIVE: To study the association between various fetal congenital
malformations and the biophysical profile (BPP), we tested the following
hypotheses: (1) a specific organ system malformation is associated with the
absence of one or more BPP parameters, and (2) four BPP parameters are not
affected by the advancement of fetal maturation. STUDY DESIGN: From 1985 to 1995,
316 fetuses with congenital malformations and 351 controls were identified in a
high-risk population undergoing ultrasound examinations of anatomic structures
and biophysical profile evaluations. For investigation of the influence of fetal
maturity on biophysical profile evaluations, both the malformed fetuses and the
controls were stratified into two gestational-age groups, 26-34 weeks and > 34
completed weeks. Four parameters of the BPP, including (1) fetal breathing, (2)
gross fetal movements, (3) fetal muscle tone, and (4) quantitative amniotic fluid
volume, were divided into low (0-6) and high (8) total score subgroups. Tests of
significance were done using chi 2 analysis, Student's t test or Fisher's exact
test, as appropriate. Level of significance was set at P < .05. RESULTS: When
comparing malformed fetuses to controls, the malformed group had a statistically
significantly higher percentage of low BPP scores due to absent fluid, tone or
breathing. Fetuses with a musculoskeletal anomaly were statistically
significantly more likely to lose points for fetal movement (P < .02); fetuses
with a genitourinary system anomaly lost points for fluid (P < .001), tone (P <
.005) and breathing (P < .005); fetuses with a central nervous system anomaly
lost points for tone (P < .02) and breathing (P < .001); and fetuses with a
thoracic anomaly lost points for breathing (P < .002). There was no statistically
significant difference in BPP scores between fetuses at 26-34 weeks' gestational
age and fetuses > 34 completed weeks' gestational age. CONCLUSION: The two
hypotheses were confirmed by the study results.
PMID- 9653700
TI - Laparoscopic radical hysterectomy with low paraaortic, subaortic and pelvic
lymphadenectomy. Results of short-term follow-up.
AB - OBJECTIVE: To describe a detailed operative procedure for type III laparoscopic
radical hysterectomy with bilateral low paraaortic, subaortic and pelvic
lymphadenectomy. STUDY DESIGN: Between January 1992 and December 1995, eight
patients with cervical carcinoma IA2 or IB1 underwent laparoscopic radical
hysterectomy at China Medical College Hospital, Taichung, Taiwan, R.O.C. The
procedure of laparoscopic radical hysterectomy was separated into eight segmental
steps. RESULTS: No major complications, including ureteral injury and lymphocyst
formation, were noted in any case. Mean hospitalization was 6.5 days. The follow
up period ranged from 16 to 62 months. Only one case recurred, in the lung.
CONCLUSION: Laparoscopic radical hysterectomy is a safe procedure. A complete
pelvic and paraaortic lymphadenectomy and type III radical hysterectomy can be
performed laparoscopically. This approach allows shorter hospitalization and
carries less morbidity than the open type. Short-term follow-up (1.3-5.1 years)
indicated a favorable prognosis.
PMID- 9653701
TI - Lectin histochemistry of fallopian tube epithelial cells. Relation to ovum
transport and ovum pickup.
AB - OBJECTIVE: Data on histochemical and biochemical characteristics of the human
oviduct are scarce. The exact mechanisms of ovum transport and pickup are not
fully understood. STUDY DESIGN: Human fallopian tubes were obtained and prepared
for histochemistry. We analyzed the distribution of negatively charged groups on
the oviduct epithelium and cumulus cells and examined the distribution of
glycoconjugates by means of lectin histochemistry. We tested the possible
influence of poly-L-lysine and considered ABO blood group expression since these
characteristics are determined by specific terminal sugar residues. RESULTS: A
negatively charged glycocalyx exists on tubal epithelial cells and cumulus cells.
Adherence by affinities similar to sugar-lectin binding forces could be disproven
in case of commonly used lectins. Poly-L-lysine inhibited the cationic binding
reaction but did not influence lectin binding. The blood group A glycoprotein
presents terminal D-N-acetyl-galactosamine residues, which are demonstrated by
HPA lectin binding. CONCLUSION: Our study indicates that it is unlikely that
electrostatic interactions play a major role in ovum transport or pickup. Since
poly-L-lysine has been described as inhibiting ovum transport, sugar-lectin
binding affinities seem not to operate in ovum transport or pickup.
PMID- 9653702
TI - Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro
fertilization-embryo transfer.
AB - OBJECTIVE: To determine the effect of danazol on in vitro fertilization-embryo
transfer (IVF-ET) patients who failed to conceive in previous attempts despite
having embryos with optimal morphology, whether endometriosis is present or not.
STUDY DESIGN: In this prospective, randomized, controlled study, of 81 patients
who experienced unexplained failures of IVF-ET despite having good-morphology
embryos, 40 received danazol (400 mg/d orally for 12 weeks) following the
unsuccessful IVF-ET cycle. The next IVF-ET was performed within three months of
the first spontaneous ovulation after danazol administration. The remaining 41
patients constituted the control group, and in them the next IVF-ET was performed
within six months after the previous failed cycle. RESULTS: Conception occurred
in 16 of 40 (40%) danazol-treated patients at the subsequent cycle and showed a
significant increase when compared with 8 of 41 (19.5%) control subjects (P <
.05), though the number of embryos with optimal morphology decreased after
danazol treatment. CONCLUSION: Danazol may be used for patients who have had
repeated failures of IVF-ET despite having morphologically optimal embryos and
may be useful for increasing receptivity of the endometrium in these patients.
PMID- 9653703
TI - Vernix caseosa peritonitis as a rare complication of cesarean section. A case
report.
AB - BACKGROUND: Vernix caseosa peritonitis is a rare complication of cesarean section
with distinctive histopathologic findings. CASE: Vernix caseosa peritonitis
occurred in a 28-year-old, pregnant woman following emergency cesarean section.
Exploratory laparotomy revealed right subphrenic and perihepatic fluid
collections with multiple small abdominal abscesses. Cytopathologic examination
of the peritoneal lavage specimen showed a purulent inflammatory exudate admixed
with occasional squamous debris, portions of hair shafts, meconium pigment, and
foamy and multinucleated giant cells. During hospitalization the patient had
developed Clostridium perfringens acute endometritis, presumably due to
aggressive treatment with broad-spectrum antibiotics. CONCLUSION: Pathologists
are in a unique position to make the correct diagnosis in an otherwise-ambiguous
clinical presentation because of the distinctive histopathologic and
cytopathologic findings of this entity. Computed tomography-guided fine needle
aspiration cytologic evaluation can be diagnostic in such cases.
PMID- 9653704
TI - The lithium ion: a foundation for psychopharmacological specificity.
AB - The idea of lithium's specificity for bipolar disorder was proposed in Cade's
original work in 1949. Since then, many controlled studies have been performed,
examining lithium for treatment of bipolar disorder and other psychiatric
conditions. This review was undertaken to determine if the suggestion of
lithium's specificity has support in the controlled studies conducted after
Cade's initial proposal. Studies were selected in a Medline search, dating back
to 1966 and also identified from the bibliography of some of these papers. The
controlled trials with lithium for the treatment of mania and bipolar depression,
unipolar depression, schizophrenia, and schizoaffective disorder were reviewed.
The published studies with lithium in other neuropsychiatric conditions were also
considered. Additionally, we reviewed literature on other therapeutic agents
proposed for bipolar disorder, looking at their comparative effectiveness to
lithium. The data analyzed give strong support for lithium's being most effective
in bipolar disorder, with minimal or no therapeutic effects in other
neuropsychiatric disorders. The neurochemical underpinnings of this specificity
are being investigated, without conclusive findings to date. The study of this
paradigm of specificity in neuropsychopharmacology research may lead to
meaningful contributions to understanding the pathophysiology of bipolar disorder
and may help to develop newer treatments for this condition.
PMID- 9653705
TI - Has the effectiveness of lithium changed? Impact of the variety of lithium's
effects.
AB - Lithium treatment, initially considered specific for bipolar disorder, has since
been shown to provide additional benefits in affective and other disorders. This
variety of benefits should be taken into account when interpreting recently
reported lower efficacy during lithium prophylaxis, as well as early relapses and
loss of efficacy after lithium discontinuation. There are particularly striking
parallels between these recent reports and earlier observations of
"antipsychotic" lithium effects. Other factors, such as the accumulation of
atypical, treatment-resistant patients in academic centers and, in particular,
the broadening of diagnoses of affective disorders, further complicate the
interpretation of the recent reports. Lithium, however, continues working well
for patients with typical bipolar disorders, for whom it was originally proved
effective.
PMID- 9653706
TI - Bipolar disorders in DSM-IV: impact of inclusion of rapid cycling as a course
modifier.
AB - In this paper, we review the process for inclusion of rapid cycling as a course
modifier to bipolar disorders in DSM-IV. This process involved definition of
bipolar II disorder, delineating the duration of manic episode for bipolar I
disorder, and clarification of the diagnosis of cyclothymic disorder and mixed
mania.
PMID- 9653707
TI - New concepts in mood stabilization: evidence for the effectiveness of valproate
and lamotrigine.
AB - Recognition of limited overall benefits from lithium in bipolar disorder, with
even greater disadvantages in more severe forms of the disease, has spurred
interest in alternative therapies. A long history of development of evidence for
the utility of valproate has culminated in well-designed, placebo-controlled
studies that establish the efficacy of the divalproex form of valproate in acute
mania. Generally positive, but as yet not conclusive, studies indicate continued
benefits in prophylactic treatment of bipolar disorder. The spectrum of efficacy
of valproate is somewhat broader than that of lithium, extending to patients with
certain more severe forms of the illness; e.g., mixed manics. Pretreatment plasma
GABA activity was positively correlated with magnitude of improvement in manic
symptomatology with divalproex. The evidence of comparable clinical benefits for
lithium and valproate has stimulated studies that indicate overlapping effects on
specific G protein-linked signal transduction for lithium and valproate, but not
for carbamazepine. The possibility that additional antiepileptic drugs might have
efficacy in bipolar disorder has encouraged early clinical studies with several
newer antiepileptic drugs. Preliminary evidence for the efficacy of one of these,
lamotrigine, has been presented.
PMID- 9653708
TI - Lithium--early development, toxicity, and renal function.
AB - The report of the effectiveness of lithium in the treatment of mania by John Cade
was followed by a number of studies confirming his observations and developing
guidelines for safe and effective use. Premature rejection of lithium on safety
grounds denied many patients the benefit of treatment and may have cost more
lives than it saved. A similar safety alarm was triggered by reports of kidney
damage in the late 1970s. Subsequent reports have questioned the significance of
anatomical findings, and functional impairment and relationship to lithium
treatment. Recent findings support the conclusion that progressive impairment of
glomerular and tubular function in patients during lithium maintenance is the
exception rather than the rule and is related more to lithium intoxication,
maintenance plasma lithium levels, concurrent medications, somatic illness, and
age than on time on lithium. Guidelines for lithium use and monitoring of renal
function are outlined.
PMID- 9653709
TI - Beyond lithium in the treatment of bipolar illness.
AB - Dramatic changes have recently occurred in the availability of treatment options
for bipolar illness. Second generation mood stabilizing anticonvulsants
carbamazepine and valproate are now widely used as alternatives or adjuncts to
lithium. High potency benzodiazepines are also used as alternatives to typical
neuroleptics, and now atypical neuroleptics are demonstrating efficacy and better
side-effects profiles than the typicals. Thyroid augmentation strategies and
dihydropyridine L-type calcium channel blockers require further clinical trials
to define their role. Putative third generation mood stabilizing anticonvulsants
lamotrigine, gabapentin, and topiramate have unique mechanisms of action and
deserve further systematic study, as does the potential role for nonconvulsive
brain stimulation with repeated transcranial magnetic stimulation (rTMS). These
and a host of other potential treatment options now require a new generation of
clinical trials to help identify clinical and biological markers of response and
optimal use alone and in complex combination therapeutic regimens.
PMID- 9653710
TI - Behavioral reversal of lithium effects by four inositol isomers correlates
perfectly with biochemical effects on the PI cycle: depletion by chronic lithium
of brain inositol is specific to hypothalamus, and inositol levels may be
abnormal in postmortem brain from bipolar patients.
AB - The inositol depletion hypothesis of lithium (Li) action has been criticized,
because depletion of inositol after chronic Li treatment has not been
reproducible, effects of inositol to reverse Li-induced behaviors occurred also
with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in
brain and hard to relate to the pathogenesis of affective disorder. Therefore, we
review our studies showing that lithium depletion of brain inositol occurs
chronically in the hypothalamus, a region not previously examined; that
behavioral effects of four different inositol isomers including epi-inositol
correlate perfectly with their biochemical effects; and that inositol in
postmortem human brain is reduced by 25% in frontal cortex of bipolars and
suicides as compared with controls. Because inositol in postmortem brain is
reduced and not increased in bipolar patients, the relationship between inositol,
lithium, and affective disorder is complex.
PMID- 9653711
TI - Effects of lithium on cAMP-dependent protein kinase in rat brain.
AB - We have investigated the effects of lithium treatment on cAMP-dependent protein
kinase in discrete brain areas of rat by using photoaffinity labeling as well as
western blotting. Lithium administered for 5 weeks resulted in a significant
increase of the cAMP binding to the 52 kDa cAMP-receptor in the soluble, but not
in the particulate, fractions of both hippocampus and frontal cortex. Moreover,
immunoblotting experiments revealed that chronic lithium treatment significantly
increased the immunoreactivity against the regulatory and the catalytic subunits
of the cAMP-dependent protein kinase in the soluble fraction of both brain areas.
In contrast, no appreciable effect was observed in the particulate fractions.
Short-term lithium treatment induced a significant increase in the immunolabeling
of the catalytic subunits in the soluble fraction of both areas; whereas, the
regulatory subunits and the actin were unchanged. In the particulate fractions,
short-term lithium treatment did not elicit any substantial modification. Taken
together, the results of the present study add to the growing evidence indicating
that components of the cAMP signalling could play a crucial role in the
biochemical action of lithium.
PMID- 9653712
TI - Reductionism and antireductionism.
AB - Reductionism is the idea that all of the complex and apparently disparate things
we observe in the world can be explained in terms of universal principles
governing their common ultimate constituents: that physics is the theory of
everything. Antireductionism comes in two varieties: epistemological and
ontological. Epistemological antireductionism holds that, given our finite mental
capacities, we would not be able to grasp the ultimate physical explantation of
many complex phenomena even if we knew the laws governing their ultimate
constituents. Therefore we will always need special sciences like biology, which
use more manageable descriptions. There may be controversy about which special
sciences cannot be replaced by reduction, but that there will be some is
uncontroversial. Ontological antireductionism holds, much more controversially,
that certain higher-order phenomena cannot even in principle be fully explained
by physics, but require additional principles that are not entailed by the laws
governing the basic constituents. With respect to biology, the question is
whether the existence and operation of highly complex functionally organized
systems, and the appearance of self-replicating systems in the universe, can be
accounted for in terms of particle physics alone, or whether they require
independent principles of order.
PMID- 9653713
TI - Reductionism in physical sciences.
AB - The idea of reductionism in physical sciences is that all physicochemical
observables can be described in terms of a limited number of particles and their
variable energies. Here we limit ourselves to atomic descriptions showing how
very successful reductionism is in treating equilibrium systems. This includes
all properties of single molecules, even DNA, and can be extended to dynamic
assemblies of molecules through the variables composition, potential energies,
kinetic energies (temperature) and volume (pressure). This description includes
the capacity of a system to change, to do work. It does not include working or
changing systems when we have to consider time-dependent variables such as
directed motion, flow. Analysis of such accidentally or purposefully directed
activity seems, to the author, to be outside the above reductionist analysis in
that its feature is organization around a 'plan' or a 'cycle'. Thus reductionism
fails to describe machines, man-made or biological, in that the parts are
arranged, even dedicated, to a total function.
PMID- 9653714
TI - Macromolecular structure and self-assembly.
AB - The output from the molecular biology revolution has grown steadily and
logarithmically from the first protein sequence, insulin (Ryle AP et al 1955
Biochem J 60:541-556), the first three-dimensional atomic structure of a
macromolecule, myoglobin (Kendrew JC et al 1960 Nature 185:422-427), the first
DNA gene sequence, phi X174 gene J (Sanger F et al 1977 Nature 265:687-695) and
the first genome sequence for a free-living organism, Haemophilus influenzae
(Fleischmann RD et al 1995 Science 269:496-512) to the current situation where
the output rate is close to one new gene sequence every few minutes, several new
three-dimensional structures a day and a new (bacterial) genome completed every
few months. Those working in this field must readjust their horizons to this
changing situation every year or two. In the area of three-dimensional structure
of macromolecules and macromolecular assemblies, the methods of X-ray
crystallography, nuclear magnetic resonance and electron microscopy have combined
to produce powerful insights into how these molecular machines work. In this
paper, I present three examples of molecular machines whose structure tells us a
lot about how they work. These are the light-driven proton pump
bacteriorhodopsin, the ATP synthetase molecule which contains a tiny motor and
generator, and the flagellar rotary motor which provides the thrust to power
physical movement of the bacterial cell. The structure itself in three
dimensional detail is thus often seen to provide the most important single
insight into how things work, reducing biology to chemistry and physics. The
reductionist approach in this field seems to be limited only by the accuracy by
which it is possible to describe inter- and intra-molecular interactions in terms
of hydrogen bonds, van der Waals interactions and electrostatic forces. At
present, there is no fundamental limit in sight.
PMID- 9653715
TI - Reduction and integration in understanding the heart.
AB - The heart provides an excellent example of the limits of the reductive approach.
Cardiac cells function through the interaction of a very large number of ion
transporters, and the processes that link these to metabolic states and to
contraction. Yet, the great majority of the advances made recently have been at
the cellular and molecular levels. The pressing problem now is to begin to
understand the highly complex interactions that create physiological function at
a cellular level and, in turn, to understand the way in which large numbers of
cells interact to produce the activity of the whole heart. Many kinds of
arrhythmia, for example, can only be understood at the whole organ level.
Successful interventions using drugs designed to treat cardiac disease depend on
an integrative understanding, which at present we do not have. This is one of the
reasons why clinical trials of drugs treating cardiac arrhythmias have been
spectacularly disappointing. This paper illustrates some of these problems by
analysing normal and abnormal heart rhythms, and by focusing on one particular
transporter, the sodium-calcium exchanger, that is deeply involved both in normal
calcium balance in the heart and in the generation of pathological states,
including life-threatening arrhythmias. It will be shown that some surprising
counterintuitive results appear when computations are done at an integrative
level.
PMID- 9653717
TI - Reductionism and explanation in cell biology.
AB - It is likely to be impossible or very difficult to provide a detailed description
of the molecular interactions underlying all cellular phenomena. However, methods
and ways of thinking are now available or being developed that can deal better
with the complexity and greater extension in space and time found at the level of
the cell. This will lead to the identification of some components or groups of
components as being of particular importance for a cellular phenomenon which can
then be studied in detailed molecular terms. In other cases detailed molecular
characterization may be replaced by a logical description of the process which
emphasizes the information flow and processing rather than the nature of the
individual components and their interactions. This may provide an adequate
explanation for an appropriate understanding of the cellular phenomena involved.
PMID- 9653716
TI - Muscle contraction.
AB - Understanding muscle contraction goes to the heart of one of the fundamental
questions posed by classical philosophy, namely the nature of the pi nu epsilon
upsilon mu alpha psi nu chi iota kappa omicron nu. The nature of 'understanding'
has altered greatly during the last two millenia, particularly in response to the
development of the concept of energy. Moreover, understanding contraction depends
on understanding muscle structure. Galen was the first to make a detailed
anatomical examination of the mode of action of muscles and recognized the heart
as a muscle, but this line of research was not pursued until Leonardo da Vinci
rediscovered it 1400 years later. Vesalius used the phrase Machina Carnis, but it
was first Descartes who proposed a neuromuscular machine. However, the level of
understanding of the physiology of muscle depends critically on the resolution of
the available anatomy. Radical new insight was provided by electron microscopy.
But an understanding at a physicochemical level is only possible if the
structures of the components are known at atomic resolution. These have become
known in the last five years and have led to dramatic progress. The present level
of understanding of muscle is a physicochemical explanation of how the hydrolysis
of ATP by the component proteins actin and myosin leads to movement.
PMID- 9653718
TI - Biological computation.
AB - It is argued that biological systems can be viewed as special computing devices.
This view emerges from considerations of how information is stored in and
retrieved from the genes. Genes can only specify the properties of the proteins
they code for, and any integrative properties of the system must be 'computed' by
their interactions. This provides a framework for analysis by simulation and sets
practical bounds on what can be achieved by reductionist models.
PMID- 9653719
TI - Reductionism in learning and memory.
AB - This chapter examines the successes and (at least for now) failures of
reductionist approaches in dealing with the problem of learning and memory.
Beginning with the work of Pavlov on classical conditioning and the theoretical
work of Hebb, the paper traces the contributions made by studies on Aplysia,
Drosophila and long-term potentiation in the mammalian hippocampus.
PMID- 9653720
TI - Hearing.
AB - The aim of this chapter is to describe some of the features of the processing of
the auditory world and how different levels of explanation are appropriate to the
understanding of hearing. The working of the inner ear is best seen as a the
operation of a purposefully structured machine for the extraction of biologically
meaningful components from a sound. Physical scales determine in large part the
appropriate description of the auditory system.
PMID- 9653721
TI - The nested networks of brains and minds.
AB - The reductionist approach to the brain shows promise of revolutionizing our ideas
about what single neurons can do. A spine on a cortical pyramidal cell is about
the size of a single Escherichia coli, and if the internal machinery of a spine
is anything like as well organized as that of E. coli, the whole pyramidal cell
with its 5000 spines must be capable of computations an order of magnitude more
complex than those demanded of the neurons used for current models of the brain.
These computations might enable single neurons to detect spatiotemporal patterns,
i.e. Hebb's 'phase sequences'. Reductionism is apparently limited because its
drive is to look for explanations at lower levels in the organizational tree. For
this purpose it often uses isolated preparations in which such lower levels can
be studied but higher levels cannot, because they have been thrown down the sink.
Reductionism will never lead us to understand organization and interaction in
parts discarded or ignored, and this must include the interactions between
individual human minds that are crucial for understanding human society. Our
brains possess a 'commentary system', a mechanism that can make reports on the
internal status of some parts of the brain. This makes possible networks of
minds, and the present meeting is such a network whose interactions are being
recorded for posterity. On a grander scale such networking creates a cultural
forum where communal goals and purposes are formulated, disseminated, modified,
and often perpetuated in lasting form. The resulting group behaviour has obvious
survival value, and is perhaps the feature that distinguishes humans most clearly
from other species.
PMID- 9653722
TI - Genes, environment and the development of behavior.
AB - Explanations of where our behaviour comes from are frequently presented in terms
of the exclusive importance of one set of factors, either genetic or
environmental. Unravelling the external and internal sources of individual
differences is a useful first step in analysing behavioural development.
Nevertheless, the analytical method that was well designed for extracting
influences from a confusing mass of data was never a substitute for a theory. It
was simply a means to an end. Descriptive statements about the genetic and
environmental sources of variation in the population do not offer an adequate
basis for understanding what happens to individuals. That awareness was an
important step in moving towards an adequate theory of behavioural development.
As an example of how that may be done, I discuss the interplay between the
developing individual and its environment in highly regulated learning processes
such as imprinting. Getting the level of explanation right is crucial. A purely
molecular or synaptic account of the processes involved in the development of
behaviour is inadequate. Nevertheless, those connectionist models that are
properly rooted in a thorough knowledge of behaviour and physiology do provide a
promising route out of the reductionism and the empty interactionism that
characterized the old nature-nurture debates.
PMID- 9653723
TI - What is wrong with reductionist explanations of behaviour?
AB - Methodological reductionism has served biology well, but its problems in the
study of behaviour include turning open systems into closed ones, defining the
units of analysis, and interpreting correlative and causal relationships between
processes studied within different biological discourses, from molecular biology
to psychology The problems become more acute when methodological becomes
philosophical reductionism, with its declared goal of collapsing 'higher level'
explanations into 'lower level' ones. Quite apart from the vexed question of what
constitutes a 'level', relevant behavioural phenomena may only be manifest at
such higher levels. The reductionist programme assumes that parts have
ontological and possibly historical (developmental, evolutionary) primacy over
wholes, yet the nature of living systems is such that this cannot be the case. I
will exemplify these problems in the context of the study of behaviour. But the
worst problem arises when reductionism becomes an ideology, especially in the
context of human behaviour, when it makes the claims to explain complex social
phenomena (e.g. violence, alcoholism, the gender division of labour or sexual
orientation) in terms of disordered molecular biology or genes. In doing so,
ideological reductionism manifests a cascade of errors in method and logic:
reification, arbitrary agglomeration, improper quantification, confusion of
statistical artefact with biological reality, spurious localization and misplaced
causality.
PMID- 9653724
TI - Levels of organization in ecological systems.
AB - Broadly speaking, ecology seeks to understand the structure and dynamics of
individual populations of plants and animals, of communities of interacting
populations, and of ecosystems. Ideally--the reductionist dream--it would be nice
to build such an understanding of how individual populations respond to
disturbance upon a fundamental understanding of the behaviour and physiology of
the constituent individuals. This is vastly ambitious. In practice, most
successful applications of population biology, for instance to the management of
harvested systems or to the control of pests and pathogens, have treated the
population itself as the basic variable (in equations whose parameters are
assessed phenomenologically, even though they are in principal derivable from the
more basic parameters pertaining to the behavioural ecology of individuals). By
the same token, studies of the structure and function of communities and
ecosystems are often and usefully approached phenomenologically as things in
themselves (topology of food webs, 'plumbing diagrams' of energy flows, etc.)
rather than being derived in a more fundamental way from detailed consideration
of the interaction among the constituent populations. Furthermore, at every level
of approach, it is often difficult to perform meaningful experiments which
control variables and isolate single factors in a tidy way. Frequently, the
spatial or temporal scale is such that observational data and/or past records
provide the only way to estimate parameters. In the 1970s and early 1980s this
inability of much of ecology to conform rigidly to simplistic schemes of 'how
science is done' caused much angst. In this paper I offer a grandly opinionated
overview of these issues.
PMID- 9653725
TI - The units of selection.
AB - Darwin's idea of evolution by natural selection is almost universally accepted by
biologists, but debate continues about the units of selection. The history of
this debate starts with Wynne-Edwards' arguments for group selection, and
Hamilton's explantation of social behaviour in terms of the inclusive fitness of
individuals. Hamilton's approach differs from the gene-centred approach pioneered
by Williams and Dawkins, although both the problem and its solution are
essentially the same. The choice of approach depends on conceptual and
mathematical simplicity, and on one's attitude to the causal efficacy of genes.
The problem of selection on units above the species level is discussed. Today, we
are in the main concerned with cases in which selection acts simultaneously at
two levels. This is true of current research on intragenomic conflict and of the
suggestion by Maynard Smith and Szathmary that in the major transitions in
evolution, entities that were capable of independent replication before the
transition can only replicate as part of a larger whole after it.
PMID- 9653727
TI - "Hot beds of disease": malaria and civilization in nineteenth-century British
India.
AB - Malaria control was a relatively low priority for the British in India: despite
being the principal cause of sickness and death among the Indian people, malaria
affected the colonial economy only indirectly and, unlike epidemics of cholera or
plague, presented few challenges to public order. Nevertheless, malaria was an
important disease: not only in terms of its effects upon the health and
livelihood of the indigenous population, but also in the language and politics of
colonial rule. Malaria was a signifier of India's "backwardness" and its
prevention was closely associated with the mission to "civilize" and tame the
Subcontinent. But the gap between this rhetoric and the reality of colonial
policy was unconvincingly wide, and the Government of India's failure to tackle
the problem of malaria was increasingly criticised by imperialists and
nationalists alike.
PMID- 9653726
TI - The particular and the general. Issues of specificity and verticality in the
history of malaria control.
AB - Several ideas have currency through long periods of malaria control history and
important issues in controlling many communicable diseases have often been fought
out over malaria. Health administrators view complex problems of malaria control
through these apparently simple ideas. The most important concepts concern the
need for specific methods to combat particular features of the spread of malaria
and how far this is reflected by the development of specific health services.
This paper follows these ideas through the last century and argues that the dead
hand of history has played too large a role in determining malaria control
generally, and especially over the last two decades, while the whole period
provides an illuminating commentary on conceptualization in tropical health and
its evolution. The two decades following discovery of the mosquito transmission
of malaria saw increasingly specific knowledge about the vectors and approaches
to preventing breeding. This required "odd" health workers who poured oil on
water and did fresh-water biology and later special engineers who could design
reservoirs and irrigation systems hostile to anopheline breeding and apply
"species sanitation". The expertise required lay outside the health sector.
Later, the DDT phase focused on a single highly specialized control technique,
total coverage house spraying, and led on to attempted eradication, whose
activities were vertically grouped. Malaria eradication became autonomous within
the health department. It became the archetypal vertical programme whose funding
levels and early successes made it a model to be emulated. But the need for
active case surveillance to be integrated with general health services was a
major reason for failure in some countries. The subsequent reaction to failed
eradication emphasized horizontal or general health services, and these are very
relevant to current pre-occupations with morbidity and mortality reduction by
early diagnosis and prompt treatment. The future needs a complex mixture of
interventions that cut across traditional views of either specificity or of the
horizontal/vertical split in programmes, and development of effective control
with imperfect tools requires a more sophisticated analysis of control methods
and organizations than is provided by a simple vertical/horizontal debate.
PMID- 9653728
TI - "Reasons for contentment": malaria in India, 1900-1920.
AB - Although Ronald Ross carried out his pioneering investigations on the role of the
mosquito in the transmission of malaria in India, antimalarial activities in the
sub-continent were disappointing. After the unsuccessful attempt at mosquito
control at the military cantonment at Mian Mir (near Lahore, present day
Pakistan), quinine prophylaxis was adopted as a compromise solution. While this
strategy also failed, a good deal of important work was carried out in India in
the first two decades of the twentieth century, so that by the 1920s, the
magnitude of the malaria problem was fully appreciated.
PMID- 9653729
TI - Antimalarial work in China: a historical perspective.
AB - Systematic scientific studies of malaria in China did not begin until the 1920s.
The persistence of misconceptions about the disease and the absence of political
stability, funds and trained personnel were obstacles to any large scale
antimalarial campaigns. In the 1920s and 30s, antimalarial efforts involved
epidemiologic studies, environmental alterations, and treatment of patients.
During the Sino-Japanese War when the Chinese government relocated inland,
China's antimalarial work focused on the control of the disease, especially in
the western and southwestern provinces. After the founding of the People's
Republic of China in 1949, nationwide antimalarial campaigns were initiated and
enforced by the central government which also promoted intersectoral and
interregional cooperation. Together with the building of a preventive and anti
epidemic infrastructure and health care system as well as the training of
personnel, the government used techniques of mass mobilization to launch programs
of vector control and mass therapy. Provinces were also organized into
antimalarial regional alliances to facilitate malaria control and surveillance.
PMID- 9653730
TI - Ecology, economics and political will: the vicissitudes of malaria strategies in
Asia.
AB - The documented history of malaria in parts of Asia goes back more than 2,000
years, during which the disease has been a major player on the socioeconomic
stage in many nation states as they waxed and waned in power and prosperity. On a
much shorter time scale, the last half century has seen in microcosm a history of
large fluctuations in endemicity and impact of malaria across the spectrum of
rice fields and rain forests, mountains and plains that reflect the vast
ecological diversity inhabited by this majority aggregation of mankind. That
period has seen some of the most dramatic changes in social and economic
structure, in population size, density and mobility, and in political structure
in history: all have played a part in the changing face of malaria in this
extensive region of the world. While the majority of global malaria cases
currently reside in Africa, greater numbers inhabited Asia earlier this century
before malaria programs savored significant success, and now Asia harbors a
global threat in the form of the epicenter of multidrug resistant Plasmodium
falciparum which is gradually encompassing the tropical world. The latter
reflects directly the vicissitudes of economic change over recent decades,
particularly the mobility of populations in search of commerce, trade and
personal fortunes, or caught in the misfortunes of physical conflicts. The period
from the 1950s to the 1990s has witnessed near "eradication" followed by
resurgence of malaria in Sri Lanka, control and resurgence in India, the
influence of war and postwar instability on drug resistance in Cambodia, increase
in severe and cerebral malaria in Myanmar during prolonged political turmoil, the
essential disappearance of the disease from all but forested border areas of
Thailand where it remains for the moment intractable, the basic elimination of
vivax malaria from many provinces of central China. Both positive and negative
experiences have lessons to teach in the debate between eradication and control
as alternative strategies. China has for years held high the goal of "basic
elimination", eradication by another name, in sensible semi-defiance of WHO
dictates. The Chinese experience makes it clear that, given community
organization, exhaustive attention to case detection, management and focus
elimination, plus the political will at all levels of society, it is possible
both to eliminate malaria from large areas of an expansive nation and to
implement surveillance necessary to maintain something approaching eradication
status in those areas. But China has not succeeded in the international border
regions of the tropical south where unfettered population movement confounds the
program. Thailand, Malaysia and to an extent Vietnam have also reached essential
elimination in their rice field plains by vigorous vertical programs but fall
short at their forested borders. Economics is central to the history of the rise
and fall of nations, and to the history of disease in the people who constitute
nations. The current love affair with free market economics as the main driving
force for advance of national wealth puts severe limitations on the essential
involvement of communities in malaria management. The task of malaria control or
elimination needs to be clearly related to the basic macroeconomic process that
preoccupies governments, not cloistered away in the health sector Historically
malaria has had a severe, measurable, negative impact on the productivity of
nations. Economic models need rehoning with political aplomb and integrating with
technical and demographic strategies. Recent decades in Chinese malaria history
carry some lessons that may be relevant in this context.
PMID- 9653731
TI - The role of chemotherapy in early malaria control and eradication programmes in
Thailand.
AB - The use of synthetic antimalarial compounds played a secondary role to the use of
residual insecticides in post World War II antimalarial control and eradication
campaigns. The discovery of chloroquine-resistant malaria in South East Asia and
South America prompted an intensification of antimosquito measures, rather than a
thorough investigation of resistance. It was the failure of the antimosquito
measures which primarily called a halt to malaria eradication and a return to
control. A focus on the role of synthetic antimalarials in Thailand thus aims to
provide a complementary view to those histories being constructed around the
antimosquito measures.
PMID- 9653732
TI - Malaria control in Papua New Guinea in the Second World War: from disaster to
successful prophylaxis and the dawn of DDT.
AB - Australian forces were involved in warfare in hyperendemic areas of New Guinea
from early 1942 until late 1945. Initially they were ill-prepared and suffered
very heavy malaria casualties, even when not engaged in fighting. As a result
measures were taken to make the supervision of personal protection (clothes,
suppressive atebrin, repellent, mosquito nets) a matter for unit commanders
rather than a medical problem. Malariologists were appointed and supervised
Malaria Control Units, which were moved in with attacking troops, and
Entomological Sections were established, which provided advice on vectors of
malaria and other arthropod-borne diseases. In successive campaigns the
casualties from malaria decreased substantially, especially after active
operations in particular campaigns had ended, except in the Aitape-Wewak area,
where field observations suggested that some strains of P. falciparum were
resistant to the standard dose of suppressive atebrin. This was confirmed in
experiments on human volunteers at a malaria research unit in Australia.
PMID- 9653733
TI - Malaria in New Guinea during the Second World War: the Land Headquarters Medical
Research Unit.
AB - In June 1943 arrangements were made to carry out experiments on malaria
suppressive drugs on human volunteers in Cairns, in north Queensland, under the
direction of Brigadier Neil Hamilton Fairley; early in 1944 the Land Headquarters
Medical Research Unit was established to continue this work. Using 868 healthy
volunteers and 317 infected soldiers and A. punctulatus mosquitoes flow in from
New Guinea or bred locally, several suppressive drugs were tested. Doses of 10
grains of quinine daily failed to suppress New Guinea strains of P. falciparum
and were only partially effective against P. vivax infections, whereas 100 mg of
atebrin daily controlled symptoms of P. vivax infection and cured infections with
most New Guinea strains of P. falciparum, however some strains of P. falciparum
from Wewak were resistant to this dose, but were cured with double the daily
dose.
PMID- 9653734
TI - Bitter-sweet solutions for malaria: exploring natural remedies from the past.
AB - This paper explores "a wonderful cure" for malaria used successfully by Robert
Talbor, an apothecary's apprentice in the English marshes, to treat Essex
smugglers and European Royalty in the seventeenth century. The basis of this cure
is identified as "quinquina" from the bark of the South American Cinchona tree.
The story of Robert Talbor and his secret remedy for malaria opens up a set of
intriguing questions about the early history of "quinquina", the subsequent
development of quinine, the use of higher plants for antimalarial drugs,
including the Chinese plant Artemisia annua L., and the value of unlocking the
secrets of the past in our search for strategies to control malaria.
PMID- 9653735
TI - Malaria and colonialism in the German colonies New Guinea and the Cameroons.
Research, control, thoughts of eradication.
AB - German malaria research during the colonial period took place between medical and
political interests. In the field of zoological and clinical research of malaria
Germany was not a pioneer. Nevertheless, Robert Koch forced by impressive Italian
results tried to participate in malaria research on the field of acquired malaria
immunity and by optimizing the therapeutic doses of quinine in German New Guinea.
In the German Cameroons, on the other hand, the fight against malaria was
completely dominated by racial and political arguments. The paper tries to shed
light on this dichotomy, which turned out to be not very productive.
PMID- 9653736
TI - Unum facere et alterum non omittere: antimalarial strategies in Italy, 1880-1930.
AB - At the end of the XIXth Century the attitude towards malaria changed dramatically
from fatalism and resignation to an active policy that made the eradication of
the disease a possible objective. This dramatic change in the scientific
political and cultural attitudes towards malaria was the result of two main
phenomena: i) the impact of the scientific medicine and Pasteurian revolution on
medicine and health policies, and ii) the discovery of the theoretical simplicity
of the cycle of malaria transmission and of the possibility to interrupt it, by
avoiding the contacts between people and the Anopheles mosquitoes. However,
scientifically based strategies against malaria were in place before the
discovery of the real causative agents and of the transmission cycle at the end
of the XIXth century, as the origin of the scientific medicine had already
produced a 'rationale' for local and national campaigns against malaria.
According to Tommasi-Crudeli, for example, the cause of malaria was not a
'chemical compound', a 'miasma', but a 'living ferment', specific and autonomous.
As a consequence, the aim of antimalarial measures was to eliminate the
conditions indispensable to the multiplication of the specific ferment contained
in the soil. The theory of malaria aetiology changed after the discovery of the
transmission cycle by Ross and Grassi, but the general strategy remained the
same: to eliminate one of the factors indispensable to the multiplication and
diffusion of the agent. The detailed knowledge of the malaria transmission cycle
made it possible to define the exact conditions which were alone responsible for
the propagation of the disease and its persistence in the endemic areas. The
theoretical linearity and the specificity of the 'Grassi's law' was decisive and
produced a fundamental paradigmatic shift in the antimalarial policies. The
essential point for the epidemiology and prophylaxis of malaria became to clarify
the conditions which contribute to facilitate or to prevent the infection of the
Anopheles.
PMID- 9653737
TI - Socio-economic and scientific premises for forming the strategies against malaria
in Russia under Soviet power.
AB - The rapid spread of malaria in the 1920s-early '30s in the USSR was a result of
Stalin's social and demographic policy. The Soviet government needed to elaborate
the special complex of organisational and applied scientific measures concerning
the eradication of malaria. The Central Malaria Commission and a network of
antimalaria stations were created. In the 1930s and '40s malaria studies were
institutionalised. A system of Medical Research Institutes was set up in the
Soviet Union. Antimalaria congresses and periodical special issues helped
coordinate their activities. Russian parasitologists worked out new approaches
and methods of the comprehensive control of malaria foci. During World War II
(1941-1945), the epidemiological situation was aggravated and antimalaria
measures reduced. In the years 1945-1960 Beklemishev with his scientific school
worked out the concept of landscape malariology and of "vital scheme of the
species". This concept formed the basis for realising the malaria eradication
strategy. In 1961 the WHO Malaria Eradication Department ascertained the
liquidation of all types of malaria in Russia as epidemics.
PMID- 9653738
TI - Acquired immunity against malaria as a tool for the control of the disease: the
strategy proposed by the Malaria Commission of the League of Nations in 1933.
AB - The Third General Report of the Malaria Commission, printed in 1933, suggested
for the control of malaria a strategy aimed to promote the acquisition of a
"relative immunity" through a non radical treatment of the infected people living
in highly endemic areas. The paper discusses the content of the Report and
describes the scientific (empirical) premises on which it stood. Moreover, it
illustrates the criticism that was directed against the immunological strategy
and that eventually led to its abandonment.
PMID- 9653739
TI - Failure-as-success: multiple meanings of eradication in the Rockefeller
Foundation Sardinia project, 1946-1951.
AB - In the history of malaria control programs there were important tensions between
proponents of the concept of eradication and those of malaria control. In this
debate the concept of eradication has had multiple meanings. This paper concerns
the post-hoc interpretations of the outcomes of the Rockefeller International
Health Foundation-sponsored project conducted in Sardinia between 1946 and 1951.
The Ente Regionale per la Lotta Anti-Anofelica in Sardegna (regional agency for
the anti-Anopheles struggle in Sardinia) (ERLAAS) project was conceived as a
large-scale, field-based pilot demonstration project to test the feasibility of
the strategy of "species eradication" in an area with an endemic malaria vector.
Species eradication, a strategy championed by Soper, was aimed at the total
annihilation of an anopheline vector from an area. Under the leadership of the
Rockefeller Foundation, the ERLAAS project used postwar UNRRA funds to purchase
local labor and imported DDT, oil-suspension, and war-surplus equipment in an
"all-out" campaign against Anopheles labranchiae, even in sparsely populated
areas. The original aim was entirely entomological; species eradication was
expected to be completed in two years for a cost of $2.7 million. Ironically,
malaria mortality on the island had already been lowered before WWII by a series
of public health interventions. The ERLAAS project encountered severe technical
and logistical difficulties; its ultimate failure was foreshadowed in the
resignation of the first American director who doubted the feasibility of species
eradication. Ultimately, the ERLAAS project was ended after four and a half years
and an expenditure of $11.2 million. Although new malaria transmission on the
island ended the project failed to eliminate A labranchiae. Finally, the regional
government was counselled to continue mosquito control efforts; the continuation
of a substantial mosquito control program for fifty years after this famous
"malaria eradication" project runs contrary to the basic cost/benefit logic of
the eradication concept. Nevertheless, in the popular press both in the U.S. and
Italy, the project was presented and heralded as a major success in liberating
the island from the age-old stranglehold and misery of malaria. In the course of
the project, the goals of ERLAAS became transformed from species eradication to
malaria eradication; this was an important political spin that was put on the
evaluation of the program. The consequences of this tactical change in discourse
included two important facts: the contribution of the Rockefeller Foundation to
the island was exaggerated, and the legitimacy of the concept of global
eradication was maintained. In the framework of the World Health Organization and
the agreement for a global malaria eradication program, the "failure" of the
Sardinia project was seldom recognized or mentioned. The technical, economic, and
logistical problems faced by ERLAAS were very similar to the problems associated
with the end of the WHO global malaria eradication policy in 1972. The Sardinia
project is presented as a case of "failure-as-success"; an ideological
transformation was made, not simply for local political expediency, but more
importantly because of the predominance of the modernist cultural model of
"progress through technology" that characterized international Public Health in
the postwar era.
PMID- 9653740
TI - Anopheles (malaria) eradication in Cyprus.
AB - The island of Cyprus was suffering for many years from malaria fever. It was only
in 1946 when a well organised Anopheles eradication campaign started. For this
purpose the Anopheles Eradication Service was formed. Until 1949 this Service
worked on Mosquito Eradication. An official announcement about the success of
this Campaign was made on January 10th, 1950.
PMID- 9653741
TI - Eradication, control or neither? Hookworm vs malaria strategies and Rockefeller
Public Health in Mexico.
AB - Malaria's epidemiological importance in Mexico greatly exceeded that of hookworm,
but the Rockefeller Foundation (RF) paid far more attention to hookworm. Although
the RF collaborated with malaria campaigns around the world, malaria was only
incidental to the RF's activities in Mexico. The hookworm campaign, on the other
hand, involved the RF at every stage, from conceptualization and design to
financing, hiring, and day-to-day administration. This paper seeks to understand
why the RF's involvement in Mexico differed for the two diseases and what the
organizational, political, and health implications were for these divergent
approaches. Beginning in the mid 1920s the Mexican government developed a modest
anti-larval service, periodically draining and filling ditches and swamps,
dusting Paris green, petrolizing stagnant water, and administering quinine.
Following the RF's 1927 shift towards scientific investigation, it began to
sponsor small-scale malaria research, collecting climatological, entomological,
epidemiological, and clinical information. The Mexican government eagerly
petitioned the RF to join a national effort, but it was reluctant to become
involved. A National Malaria Campaign was established in 1935 under President
Lazaro Cardenas to coordinate education, sanitary engineering, and treatment. The
popular Campaign followed RF strategies even without its direct participation.
Meanwhile, the RF avidly pursued modest malaria research in Mexico, funding U.S.
investigators to conduct experiments on pesticides, mosquito-trapping, and
controversially, watering methods for rice. These efforts culminated in the
world's first field trial of DDT against louse-borne typhus and later as a
residual spray for malaria. In the end the RF used Mexico as a convenient locale
for scientific research that had global implications but only an incidental
relationship to Mexico's own Malaria Campaign. Likewise, the RF's much more
active hookworm program was more a means than an end, leading not to eradication
of the disease, but to Mexico's commitment to modern public health organization
and methods.
PMID- 9653742
TI - The dawn of DDT and its experimental use by the Rockefeller Foundation in Mexico,
1943-1952.
AB - The Rockefeller Foundation played an important early role in promoting the use of
DDT for malaria control. During World War II the Foundation helped test DDT in
the United States. North Africa and Italy. From 1945 to 1952 the Foundation
carried out an experimental anti-malaria program in Mexico as part of its global
mission to diffuse knowledge of how to control malaria-bearing mosquitoes with
DDT.
PMID- 9653743
TI - Conforming strategies of public health campaigns to disease specificity and
national contexts: Rockefeller Foundation's early campaigns against hookworm and
malaria in Brazil.
AB - The early experience of Rockefeller Foundation in Brazil, starting in 1915,
reflected the idea of extending learned experience in Southern US to a wide
international context. Health education and the creation of permanent local
health services were expressed as main guidelines for cooperation with State and
federal Brazilian agencies. Translating to the shaping of public health models
the terms of scientific hygiene associated with the pastorian revolution, RF
pictured different actions as part of a three step rationale of survey,
experiment and demonstrations. In this paper we focus on Lewis Hackett's
campaign, designed as a demonstration campaign of the "intensive method" of
hookworm control, with the final purpose of enlisting local agencies in long-term
action (1919-1924) and the malaria campaign in Rio de Janeiro State Lowlands
(1922-1928) led initially by Mark Boyd as an "experimental control work" of field
observation, campaign, control and maintenance to set guidelines to malaria
control in tropical areas. The course and ultimate results of these experiences
showed the need to adapt formal models to complex national and State-building
context and to disease specificity, leading to pragmatic adaptations in the issue
of control and eradication and on the shaping of vertical and horizontal health
services. The failure of these two experiences in terms of disease control helped
to strengthen the move, predominant in the next two decades, to vertical
campaigns with least dependency on local social and political dynamics, as in the
exemplar case of Frederick Soper's Anopheles gambiae eradication campaign (1938
1942).
PMID- 9653744
TI - The meanings of control and eradication of malaria in the Andes.
AB - For centuries Peruvians distinguished malaria from other conditions with
different names in Spanish and in the native languages because it was a frequent
occurrence in the coast and in the jungle located in the west and east of the
Andean highlands. Frequency in different local contexts generated different
meanings of malaria that appear more clearly when studying the campaigns of
control and eradication of the 20th century. These meanings played an important
role in the divisions and tensions that cross race, national integrity, and
regional identity in this Andean country. This work deals with the medical and
social dimensions of malaria's control and eradication efforts and the ways in
which they codified geographical and racial distinctions within peru. Because
malaria does not develop in the highlands, Andean migrants to the coast and the
jungle regions are particularly susceptible. Some doctors associated the disease
with Andean people, even contending that it was an indication of "Indians"
weakness. Finally, this article analyses the spread and containment of malaria in
light of the world eradication campaign initiated in the late 1950s and with
regard to mass migration, urbanization, and other 20th-century phenomena.
PMID- 9653745
TI - Water won't run uphill: the New Deal and malaria control in the American South,
1933-1940.
AB - During the 1930s the United States Government poured significant funds into
malaria control, via a variety of New Deal agencies. These projects were largely
confined to drainage of mosquito-producing wetlands. Malaria had diminished
significantly by the early 1940s, and this paper queries whether that reduction
was due to the control projects of the thirties, and, if so, whether such
projects should be a model for the current developing world, where malaria is a
growing problem today. Malaria statistics from the 1930s and 1940s are
unreliable, making this assessment, from the outset, complex. Further, the so
called "malaria projects" from the 1930s were, in fact, poorly planned "make
work" enterprises promoted by the Works Projects Administration and its ilk for
the creation of unskilled, ditch-digging jobs. The drainage work lacked the
oversight of competent engineers (many of them proving, in fact, that water
wont's run uphill), and little of the work had permanent impact as the ditches
were not maintained. Further, the work was not necessarily concentrated in
malarious areas, since the unemployed's distribution did not overlap that of
greatest mosquito density. Of the conflicting goals--unemployment relief and
malaria control--the former consistently dominated the latter. The results were
predictable. The author suggests that the depopulation of the rural south in the
late 1930s had more of an impact (albeit indirect and unintended) on the malaria
rates than did the large sums spent allegedly for the purpose of malaria control.
PMID- 9653746
TI - Cognition and the global Malaria Eradication Programme.
AB - When making a decision involves the analysis of complex cause-effect
relationships, experts are normally consulted to describe the best options
available. The global Malaria Eradication Programme relied upon the advice of a
small group of experienced malariologists; their counsel directed the most
ambitious endeavour in the history of the World Health Organisation. In this
essay 1 week to show how that group behaved with a single purpose and ultimately
grew to be greater than the sum of its parts because of the control of knowledge.
Each member of this epistemic community was willing to battle against malaria as
soon as possible--forsaking research, traditional tools, and risking disastrous
epidemics--because they believed that residual insecticides could progressively
eradicate a disease that killed millions and sapped the lives of countless more.
Alternative methods were ridiculed; and the epistemic community used their
individual prestige to insert the DDT gospel into the technical forums of the
WHO, and the power (and money) forums of the USA. Particular knowledge structures
of the post-war decade nurtured a technical solution to malaria, and we shall
explore how the WHO and the epistemic community could grow within this
environment so compatible to their praxes.
PMID- 9653747
TI - 'No other logical choice': global malaria eradication and the politics of
international health in the post-war era.
AB - In 1955 the Eighth World Health Assembly voted to initiate a program for the
global eradication of malaria. The global eradication of malaria represented a
remarkable leap of faith. Many health authorities, both within and outside the
Assembly, viewed eradication as at best fool hardy, and at worst, potentially
disastrous. To understand why the World Health Assembly went ahead with a Global
Eradication strategy, despite these concerns, it is necessary to examine the
politics of international health and development in the post-war era. This
political context shaped decisions about the adoption of DDT as a primary tool in
the fight against malaria, as well as the adoption of the Malaria Eradication
Program. It is equally important to understand how the advocates of an
eradication strategy shaped arguments and developed support for their cause in
the years leading up to the Eighth World Health Assembly meeting.
PMID- 9653748
TI - Arnoldo Gabaldon's independent path for malaria control and public health in the
tropics: a lost "paradigm" for WHO.
AB - Arnoldo Gabaldon played a critical role in the early promotion of the belief that
malaria could be eradicated in tropical countries. Under his leadership Venezuela
was able to achieve dramatic progress, but nation-wide eradication was not
realized. The path that Venezuela followed for malaria differed significantly
from the WHO eradication strategy. Also, Gabaldon's public health approach,
within which his malaria programme developed, was at odds with WHO's Basic Health
Services (BHS) approach. The paper describes these differences and shows that
approaches, similar to those subsequently pursued by Gabaldon, had been promoted
in the early years of WHO's history but were quickly subsumed by that of BHS
which came into force in 1953 and lasted until 1973. The paper concludes that, by
remaining loyal to the global eradication of malaria, malariologists isolated
themselves and lost much of their influence on the development of WHO public
health policies and approaches.
PMID- 9653749
TI - Conceptual conflict: malaria control and intermecine warfare within a London
postgraduate school.
AB - For more than twenty years after the end of World War II, uneasy relations
existed between epidemiologists and protozoologists within the London School of
Hygiene and Tropical Medicine, reflecting differences in their individual
approaches to malariology and malaria control. The paper explores the particular
problems created by the polarised views and lack of sympathy between George
Macdonald and P.C.C. Garnham throughout the 1950s and 1960s.
PMID- 9653750
TI - The end of malaria in Europe: an eradication of the disease by control measures.
AB - The success of the campaigns against malaria in Europe, the USA and other
countries in the temperate zone, prompted WHO to launch its global eradication
campaign in 1955. It failed to achieve eradication in tropical countries due to
climatic, social and economic conditions different from those prevailing in the
temperate zone, where eradication had been achieved using control measures.
PMID- 9653751
TI - Water-solid interactions. IV. Influence of moisture sorption on the compaction of
film-coated particles.
AB - The effect of moisture sorption on the compaction properties of model modified
release (MR) pellets coated with ethyl cellulose/hydroxypropylcellulose film has
been studied for the MR pellets alone and in binary mixtures with
microcrystalline cellulose, lactose alpha-monohydrate, or lactose 9% amorphous.
The in vitro dissolution rate prior to and after compaction was used as an
indirect method of evaluating the effect of exposing the MR pellets to a
compaction force. Moisture sorption as well as the glass transition temperature
(Tg) using differential scanning calorimetry (DSC) were determined as a function
of humidity for cast film conditioned at different humidities using a climate
test chamber. The compaction properties of lactose and microcrystalline cellulose
were altered by the addition of MR pellets, resulting in a robust tablet mass and
a tensile strength of the tablet masses that was less sensitive to moisture. The
amount of moisture sorbed was found to have little influence on the formation of
cracks or on the rupturing of film-coated MR pellets during compaction. This was
probably a result of both the small depression in the Tg for the film system at
increasing RH and the robustness of the film chosen. The results also showed that
the volume reduction properties of the tableting excipients were of importance
for reducing damage to the film coating. Lactose had a higher protective effect
on the film-coated MR pellets compared to microcrystalline cellulose.
PMID- 9653752
TI - A logical stepwise approach to laser diffraction particle size distribution
analysis methods development and validation.
AB - In this study, a logical, stepwise, efficient approach was used to develop and
validate particle size distribution analysis methods for 58 different
pharmaceutical bulk powders in a timely fashion. Image analysis was used to
determine particle morphology and laser diffraction particle size distribution
analysis was used to evaluate the dispersion medium, dispersion concentration,
sonication time, and dispersion stability. Ruggedness validation was performed,
by two different analysis, on different days, with different instruments on two
preparations each of two different lots of material. It was determined that if
the relative standard deviation (RSD) of the median volume diameters (d50) of the
four preparations for each lot was below 20%, the method was suitably rugged for
use in a quality control setting. Data for methyldopa, metoprolol tartrate, and
metronidazole are presented as typical method validation results for three
different modes of analysis. Data at three points (d10, d50, and d90) on the
distributions were tabulated and evaluated for all 58 methods validated. The
median volume diameter (d50) was found to be adequate for method validation. The
approach rapidly generated valid, reproducible particle size distribution
analysis methodology.
PMID- 9653753
TI - Formulation and evaluation of albuterol metered dose inhalers containing
tetrafluoroethane (P134a), a non-CFC propellant.
AB - This study was undertaken to evaluate tetrafluoroethane (P134a) as a possible
chlorofluorocarbon (CFC) replacement for albuterol metered dose inhaler (MDI)
formulations. Preformulation studies using three conventional (oleic acid,
sorbitan trioleate, lecithin) and a nonconventional (oleyl alcohol) surfactant
indicated that P134a is a poor solvent for these surfactants. A slight
improvement in the solubility of oleic acid and oleyl alcohol was observed by the
addition of low concentrations of a nonconventional cosolvent diethyl ether (< or
= 0.5% w/w). Formulation screening of the prepared albuterol formulations
indicated that suspensions containing oleyl alcohol and diethyl ether had a
slower rate of separation. Product performance of four albuterol formulations
containing oleyl alcohol, diethyl ether, and P134a was evaluated and compared to
a leading commercial formulation containing CFC propellants (Ventolin). Ventolin
showed excellent agreement between the emitted dose and the expected dose but
only a reasonable agreement was observed with one of the better P134a-containing
formulations. P134a formulations showed higher internal pressure in comparison to
the CFC formulation. The concentrations of the surfactant, drug, and cosolvent
appeared to have a significant impact on the uniformity of the emitted dose.
Determination of particle size using the time-of-flight and the laser diffraction
analyzer revealed that P134a formulations had equal or smaller particle size than
the formulation containing CFC. However, the CFC formulation showed a higher
respirable fraction than the P134a formulation when measured by the two inertial
impaction methods. The observed particle size distribution of the formulation
appeared to depend on the measuring method used.
PMID- 9653754
TI - The influence of tertiary butyl alcohol and volatile salts on the sublimation of
ice from frozen sucrose solutions: implications for freeze-drying.
AB - The purpose of this work was to investigate the phase behavior of tertiary
butanol (TBA) and volatile ammonium salts in frozen mixtures with some commonly
used excipients and the efficacy of such volatile additives in accelerating the
sublimation of ice from frozen solutions. Differential scanning calorimetry was
employed to determine first-order phase transformations and glass transition
temperatures in binary and ternary mixtures. Ice sublimation rates were studied
by conventional freeze-drying and mass loss with time. A eutectic temperature
(268 K) was identified for the anhydrous TBA-sucrose system. In frozen ternary
water-excipient-TBA systems, the relative amplitudes of the glass and phase
transitions, as measured during warming scans, were found to depend critically on
the previous cooling rates. Glass transitions of all the freeze-concentrated
mixtures used were determined. The sublimation studies indicated an ability of
all volatile additives to accelerate ice sublimation from amorphous, freeze
concentrated solutions, but no clear ranking order, applicable to all systems
studied, could be established.
PMID- 9653755
TI - A stability study involving HPLC analysis of aqueous thiorphan solutions in the
presence of human serum albumin.
AB - The stability of thiorphan (1.0 mg/ml) in normal saline containing 1% human serum
albumin (HSA) was determined in order to find the most appropriate storage
conditions. Direct liquid chromatographic analysis of this solution was feasible
through the use of a micellar chromatographic system and proved to be stability
indicating. During 8 weeks the percentages of the initial thiorphan concentration
remaining after storage at 4, 20, 30, and 50 degrees C were determined. An
Arrhenius plot was composed using the rate constants of thiorphan degradation at
these temperatures. The thiorphan solution was stable for at least 2 months if
stored at -20 degrees C. Taking into account the oxidative degradation of about
7% after thawing, we determined that the solution can be kept in a refrigerator
for 4 days. Storage at room temperature should be limited to 1 day. By
identification of the degradation products it could be concluded that thiorphan
is degraded mainly via oxidation forming disulfides. Therefore, it is recommended
that the solvent be purged with nitrogen before thiorphan is dissolved.
PMID- 9653756
TI - Formulation and characterization of calcium alginate beads containing ampicillin.
AB - The purpose of this work was the preparation and characterization of calcium
alginate beads containing ampicillin. Aqueous solutions of drug and sodium
alginate (three viscosity grades) were added drop by drop to aqueous solutions of
calcium chloride; the droplets instantaneously formed gel beads, which were then
dried. Morphological studies and drug contents, in vitro release, and erosion
tests were carried out for the characterization of the prepared beads. The dried
particles were characterized by irregular shape and a smooth or rough surface,
depending on the viscosity grade of the alginate used. The control of the drug
for different time intervals depended on the molecular weight of the polymer
used; however, the pH-change test showed that this capacity was much lower in the
case of acid-treated particles. The results obtained show that the ampicillin
beads prepared are suitable for intramammary therapy.
PMID- 9653757
TI - The synthesis and in vitro characterization of the mucoadhesion and swelling of
poly(acrylic acid) hydrogels.
AB - The purpose of this research was to synthesize insoluble, mucoadhesive hydrogels
by crosslinking linear poly(acrylic acid) with sucrose and investigate the
relationship between hydrogel crosslink density, swelling, and in vitro
mucoadhesion. A condensation reaction was employed to synthesize the hydrogels
and crosslink density was varied by altering sucrose concentration and cure time.
Equilibrium swelling at pH 7.4 was measured both gravimetrically and
geometrically. In vitro mucoadhesion was determined by a tensile technique.
Equilibrium swelling studies indicated that the crosslink density was
proportional to both sucrose concentration and duration of cure time. In vitro
mucoadhesive properties of the hydrogels improved as crosslink density increased.
This was attributed to an increase in poly(acrylic acid) chain density/unit area
of the equilibrium swollen hydrogel, which promoted interaction of the
mucoadhesive and glycoprotein polymer chains.
PMID- 9653758
TI - Detection of formaldehyde-induced crosslinking in soft elastic gelatin capsules
using near-infrared spectrophotometry.
AB - The purpose of this research was to monitor the migration of formaldehyde from a
polyethylene glycol (PEG) fill into the gelatin shell of a soft elastic gelatin
capsule (SEGC) using near-infrared (NIR) spectrophotometry. SEGCs were filled
with five solutions of aqueous formaldehyde in PEG (0, 0.05, 0.10, 0.20, and 0.40
v/v%), stored at ambient conditions for 48 hr, emptied, and scanned in NIR
spectrophotometer. Principal component regression (PCR) was employed to analyze
the spectra of the empty capsules. Good correlation was established (r2 = 0.988)
when actual concentrations of formaldehyde in the PEG fill of the capsules were
regressed against the principal component (PC) values from NIR spectra of the
emptied and washed capsules. The loadings of the first PC describe a baseline
shift in the spectra that arises from a change in water concentration. Lower PC
loadings reveal the presence of signals at 1780 and 2200 nm that are not due to
water absorbance, confirming the hypothesis that chemical bonds are formed during
the formaldehyde-induced crosslinking of the gelatin in SEGCs. Gelatin
crosslinking, initiated by formaldehyde migration from the PEG fill into the
shell of an SEGC, was detected by NIR spectrophotometry. When NIR was coupled to
principal component analysis, a linear relationship was found between the NIR
spectra of empty SEGCs and the amount of crosslinking induced by concentrations
of formaldehyde in the original fill material.
PMID- 9653759
TI - In situ salt screening--a useful technique for discovery support and
preformulation studies.
AB - The purpose of this paper was to present an in situ salt screening technique
which is applicable to most basic compounds. The theoretical aspects,
experimental details, applications, and significance of this technique are
illustrated through in situ salt screening studies performed on GW1818, an alpha
1A andrenergic receptor antagonist intended for treatment of benign prostatic
hyperplasia (BPH). Generally, the in situ salt screening technique includes (i)
acid selection, (ii) a solubility study, (iii) characterization of residual
solids, and (iv) calculation of the Ksp and solubility of the salts. Six acids
were screened for salt formation with GW1818. Excellent agreement was found
between the solubility results determined using the authentic salts and
solubility results obtained through in situ screening. Additional evidence of
salt formation and some solid state properties of the salts formed in situ were
obtained through microscopic examinations, differential scanning calorimetry
(DSC), and x-ray powder diffraction studies. Four salts of GW1818, the phosphate,
succinate, mesylate, and hydrochloride, were crystalline and demonstrated
adequate solubility. These were selected for further evaluation. Adequate
solubility was also observed in the case of citrate and tartrate salts, but these
were considered only as potential backup candidates because they were difficult
to crystallize. The results of the in situ salt screening experiments also led to
the development of an IV formulation for use in pilot toxicological studies and
pharmacological studies. In conclusion, the in situ salt screening technique
offers a time- and compound-conserving approach for prioritizing salt selection
and for providing solubility and stability information useful for formulation
development both in the research and the development stages.
PMID- 9653760
TI - Casein hydrolysate as a rapid and/or enteric dissolving additive for oral drugs.
AB - Two types of casein hydrolysates, casein A (mean peptide length 3.3) and casein B
(mean peptide length 17.4) were prepared by the enzymatic hydrolysis of casein,
and their effects on in vitro dissolution rates and oral bioavailability of drugs
were evaluated. The in vitro dissolution behavior of the kneaded mixture of three
drugs (diclofenac acid, diazepam, and prednisolone) with caseins A and B were
significantly improved compared to the drugs alone, even at 1:1 weight ratio of
drug and casein hydrolysate, even though casein A and casein B did not interact
with drug molecules in the kneaded mixture. Only diclofenac, an acidic drug,
showed an increased dissolution rate with added casein hydrolysates, and a more
rapid dissolution with casein A than with casein B was observed. When the
dissolution of prednisolone from kneaded mixture was compared at pH 1.2 and 6.8,
the dissolution rate of prednisolone from the casein A kneaded mixture was
considerably higher than that of prednisolone powder at both pHs, and the rate
from the casein B kneaded mixture was higher only at pH 6.8. The plasma
concentration-time profile showed that prednisolone was completely and rapidly
absorbed from the casein A kneaded mixture as well as the prednisolone solution.
In addition, prednisolone in the kneaded mixture with casein B was more difficult
to absorb up to 1 hr after administration in comparison to prednisolone powder.
The slow and lowered absorption of prednisolone by casein B might be explained by
conversion of casein B to a shorter soluble peptide in the gastrointestinal tract
and by the slow dissolution of prednisolone at acidic conditions. The
toxicological tests revealed that casein hydrolysate is a safe drug carrier.
Consequently, casein hydrolysates might be safely used to control the dissolution
rate and bioavailability of a variety of drugs, depending on the peptide length
of the casein fragments.
PMID- 9653761
TI - Characterization of the sucrose/glycine/water system by differential scanning
calorimetry and freeze-drying microscopy.
AB - The objective of this study was to characterize the thermal properties of systems
containing various ratios of amorphous and crystalline components using both
differential scanning calorimetry (DSC) and freeze-drying microscopy. The
glycine/sucrose system was used as a model system, since it is routinely used in
protein formulations. DSC analysis revealed that the addition of glycine to
sucrose solutions resulted in a decrease in the glass transition (T'g) of the
system. The T'g of a pure sucrose solution (7% w/v) decreased from -32.3 to -51.5
degrees C for a mixture containing a sucrose/glycine ratio of 2:5. The glass
transition of the sucrose/glycine mixture decreased linearly as more glycine was
added to the system. This decrease in glass transition resulted in severe
collapse during freeze-drying of these mixtures above T'g. However, collapse was
not observed during freeze-drying if the DSC thermogram of the sucrose/glycine
mixture exhibited a transition resulting from recrystallization of the amorphous
glycine. Mixtures having a sucrose/glycine ratio of 3:4 and 2:5 had a glass
transition of -48 degrees C and -51.5 degrees C, respectively. Despite their low
glass transition temperatures, these samples freeze-dried readily at a product
temperature > T'g using a fast freeze-drying cycle (primary drying at a shelf
temperature of +20 degrees C and chamber pressure of 100 mTorr) without any sign
of collapse. The crystallization of the amorphous glycine from the frozen mixture
of sucrose and glycine provided support during freeze-drying which prevented the
macroscopic collapse of the final product. Freeze-drying microscopy visually
revealed the crystallization and allowed for prediction of cake quality upon
lyophilization. Although the freeze-drying microscope is not as sensitive as the
DSC in detecting all transitions (it cannot detect a glass transition), it
clarifies the interpretation of DSC, and together they provide valuable
information regarding the relevance of each of the transitions to the final
freeze-dried product elegance.
PMID- 9653762
TI - Kinetic modeling for macromolecule loading into crosslinked polyacrylamide
hydrogel matrix by swelling.
AB - A kinetic model was proposed to characterize the swelling phenomenon of
polyacrylamide hydrogel and to quantify and predict the loading of insulin into
the hydrogel by swelling. Polyacrylamide hydrogel and porcine insulin were used
in the study. During swelling, the insulin concentration in the hydrogel was
found to be higher than that in the loading solution, which could be attributed
to ionization of the ionic networks, Donnan exclusion, and the possible ionic
interactions between the anionic carboxylic pendants and cationic insulin. The
experimental results demonstrated that the proposed kinetic model was able to
describe the swelling kinetics of polyacrylamide hydrogel and the loading
kinetics of insulin by using only two constants [input rate (Kin) and output rate
(Kout)]. The experimental values of Kin and Kout were found to highly depend on
the concentration of HCl. As medium pH declined (because of the addition of HCl),
the degree of swelling decreased and the insulin loading amount in the hydrogel
was reduced. A linear log-log function was observed between Kin and the volume
fraction of HCl. The Kout values also decreased with the addition of HCl, but
remained constant after more than 1% (v/v) of HCl (0.01 N) was added. The
proposed model was able to characterize the swelling kinetics of polyacrylamide
and predict the loading dose of insulin in the polyacrylamide hydrogel by
swelling.
PMID- 9653763
TI - Effect of fabrication technique on the erosion characteristics of polyanhydride
matrices.
AB - The aim of this study was to investigate the effect of device fabrication
technique on the erosion characteristics of poly[1,3-bis(p-carboxyphenoxy)
propane:sebacic acid] [p(CPP:SA)] 20:80 copolymer. Devices were prepared using
melt-molding, solvent-casting, and compression-molding techniques and their
erosion was followed by determining changes in device morphology, molecular
weight, water uptake, mass loss, and release of monomers, with time of immersion
in phosphate buffer pH 7.4 at 37 degrees C. Melt-molded devices had a very dense
and uniform structure and displayed characteristics typical of surface eroding
systems. Devices produced using a solvent-casting technique had a very porous
structure with no detectable erosion zone and the erosion profiles were
indicative of bulk rather than pure surface erosion. Compression-molded devices
had a dense structure and revealed a faster rate of erosion than melt-molded
devices. A comparison of the extent of changes of polymer molecular weight, water
uptake, mass loss, and monomer release showed a marked dependence on the method
of fabrication.
PMID- 9653764
TI - Introduction of dissolution error as a result of different openings in vessel
covers.
AB - Vessel covers are required in dissolution studies to retard solvent evaporation.
Sufficient openings on the cover are required by the current United States
Pharmacopeia (USP) "to allow ready insertion of a thermometer and for withdrawal
of specimens/samples." However, the area of the opening has not been regulated by
the USP. The purpose of this work was to measure the loss of the dissolution
solvent as a result of openings in vessel covers and to investigate errors caused
by the solvent loss. The method used in the study involved measurements of the
opening areas in three commercial vessel covers and determinations of solvent
loss under a typical dissolution condition. The results showed that the openings
in the three covers varied from 75 mm2 to 2285 mm2; this was 1-30% of the total
vessel open area for a USP standard vessel. The volume of the dissolution solvent
was reduced by 0.6-3.4% for an 8-hr dissolution study, and 1.7-9.7% for a 24-hr
study when the three different vessel covers were used. The rate of solvent loss
exhibited a linear relationship with the area of the opening in the covers. A
slower rate of reduction was found for a smaller initial volume of the solvent.
The conclusion was that higher dissolution results were produced if the solvent
loss was not considered.
PMID- 9653765
TI - Stabilization of dichloromethane-induced protein denaturation during
microencapsulation.
AB - This paper describes the denaturation of protein drugs by dichloromethane (DCM)
during the primary emulsification step of the microencapsulation process using
biodegradable polymer matrix for controlled-release application. It was found
that interaction of proteins such as tetanus toxoid (TT), diphtheria toxoid (DT),
ovine growth hormone (oGH), and human chorionic gonadotropin-based antifertility
vaccine (beta-hCG-TT) with DCM during primary emulsification stages of particle
formulation led to the precipitation of the proteins at the aqueous organic
interface with concomitant reduction in their immunoreactivity. On the other
hand, the B subunit of E. coli enterotoxin (LTB) was found to be comparatively
stable toward the denaturing action of DCM. Attempts were made to overcome the
DCM-induced denaturation by incorporation of stabilizers during the primary
emulsification step of the particle formulation. Of the many additives tested to
overcome the DCM-induced denaturation of proteins, serum albumins and polyvinyl
alcohol (PVA) showed promising results in terms of retention of the
immunoreactivity of the protein. TT stabilized by the incorporation of serum
albumin during the primary emulsification step not only showed immunoreactivity
in vitro, but also invoked antibody titers in rats comparable to those obtained
for the native protein molecules. Incorporation of 2.5% of serum albumins in the
internal aqueous phase not only protected the protein from the degradative action
of DCM but also led to stabilized primary emulsion, which is necessary for
uniform entrapment of protein drugs in the polymer matrix.
PMID- 9653766
TI - Effects of prostaglandin E1 metabolites on the induction of arterial
thromboresistance.
AB - Prostaglandin (PG) E1 has been shown to induce arterial thromboresistance in
experimental animals and in man. It is known to be degraded in vivo to
metabolites which have comparable (13,14-dihydro-PGE1) or no (15-keto-PGE1, 15
keto-13,14-dihydro-PGE1) biological activity. It was the goal of this study to
examine whether 13,14-dihydro-PGE1 and its derivatives might share biological
activity in rendering the arterial wall less thrombogenic. Using a cross
perfusion technique the aorta and iliac artery surface were exposed to a donor
rabbits' blood. We examined the intact endothelial lining and a surface which had
been deendothelialized before by means of a Fogarty catheter. Donor animals
and/or receiver animals were treated daily for 1 week with 13,14-dihydro-PGE1,
PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1, or the vehicle only,
respectively. From the group of the receiver animals, a subgroup of 6 animals
each was treated for the same period of time with either 13,14-dihydro-PGE1,
PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1, or the vehicle. Immediately after
the last administration of the respective PG or solvent, native blood from a
donor rabbit was circulated [30 mL/min. under in vivo flow conditions (60 Hz)]
over an arterial segment of a receiver animal. Deposition of 111Indium-oxine
labeled autologous platelets per surface unit was quantitatively assessed. In
vitro perfusion data were morphometrically analysed. In animals pretreated with
13,14-dihydro-PGE1 the thromboresistance was almost comparable to that achieved
with PGE1. In contrast, pretreatment of the donor animals (platelet) had only
minor effects on the thromboresistance. The other compounds showed no effects. In
vitro perfusion of human saphenous vein segments revealed PGE1 and 13,14-dihydro
PGE1 again to be of comparable potency, while 15-keto-PGE1 and 15-keto-13,14
dihydro-PGE1 were only active at concentrations being several orders of magnitude
higher. Not only PGE1 but also its in vivo formed metabolite PGE0 may play an
important role in inducing improvement of haemostatic balance via the vascular
wall rather than the platelets. The other metabolites, however, are unlikely to
exhibit an effect at biologically relevant concentrations.
PMID- 9653767
TI - Role of nitric oxide in gonadotropin-releasing hormone-dependent prostaglandin F2
alpha synthesis by frog (Rana esculenta) interrenal gland during post
reproduction.
AB - The aim of this study was to clarify the possible involvement of nitric oxide
(NO) on prostaglandin (PG) E2-9-ketoreductase activity in the gonadotropin
releasing hormone (GnRH)-dependent PGF2 alpha synthesis by the interrenal gland
of the female water frog, Rana esculenta, during the post-reproduction.
Interrenal glands were incubated in vitro with GnRH, NO donor (sodium
nitroprusside, SNP), and inhibitors of phospholipase C (compound 48/80), inositol
triphosphate (decavanadate), calmodulin (calmidazolium), NO synthase (L-NAME),
and PGE2-9-ketoreductase (palmitic acid). Production of PGE2 and PGF2 alpha and
NO synthase and PGE2-9-ketoreductase activities were determined. GnRH and SNP
increased PGF2 alpha production and PGE2-9-ketoreductase activity, and decreased
production of PGE2 and GnRH increased NO synthase activity. GnRH effects were
blocked by all inhibitors, except for palmitic acid, which did not affect NO
synthase activity, which is increased by GnRH. This study indicates that NO may
be involved in regulation of the R. esculenta post-reproduction through
stimulation of PGE2-9-ketoreductase activity in GnRH-dependent PGF2 alpha
synthesis by the frog interrenal gland.
PMID- 9653768
TI - Docosahexaenoic acid reduces both cyclic nucleotide and melatonin synthesis in
rat pinealocytes.
AB - The effect of docosahexaenoic acid (22:6n-3) on melatonin (MT) production in rat
pinealocytes was measured. In pinealocytes, supplementation with 50 microM 22:6n
3 for 48 h decreased MT production after a norepinephrine (NE)-stimulation (1 and
10 microM). Using co-treatment with IBMX (1 mM), a cyclic nucleotide
phosphodiesterase inhibitor known to increase NE-stimulated cAMP and prazosin (1
microM), an alpha 1 antagonist, the results indicate that a) 22:6n-3 did not act
on cyclic nucleotide phosphodiesterase activities to decrease both cAMP (-64%)
and cGMP (-45%) levels and b) the inhibition of cGMP was higher (-70%) in
presence of prazosin. These results confirm that in rat pinealocytes the lowering
effect of 22:6n-3 supplementation on cAMP is likely to be dependent on alpha 1
adrenoceptor modulation whereas the decrease of cGMP seems to involve other
intracellular mechanisms. The absence of 22:6n-3 effect on serotonin metabolites
suggest that the lowering effect on MT may be also correlated with alterations of
O-methylation step.
PMID- 9653769
TI - Immunoaffinity resin for purification of urinary leukotriene E4.
AB - Urinary leukotriene E4 (LTE4) has been used as an index of total leukotriene
synthesis. A wide variety of methods have been applied to measure LTE4 which has
made direct comparison of urinary levels reported by different laboratories
difficult. A new peptidoleukotriene immunoaffinity resin was utilized for urinary
LTE4 purification in a method that is easy and inexpensive, utilizing
commercially available reagents. This method is described and compared to other
methods. LTE4 (50-250 pg/mL) added to a urine extract was quantitatively
recovered using the immunoaffinity resin. Similarly, LTE4 (50-400 pg/mL) added to
urine was recovered between 63 and 76%. The coefficient of variation of samples
purified and quantified on the same or on different days ranged from 8-10%. There
was a strong correlation (r2 = 0.95) between LTE4 concentrations determined after
immunofiltration and immunoaffinity purification. Although there was a good
correlation between urinary LTE4 levels measured without purification compared to
after immunoaffinity purification, the high y-intercept of 179 indicates the
presence of interfering substances in unpurified urine. Urinary LTE4 in normal
healthy adults was 80 +/- 7 pg/mg creatinine, similar to that previously reported
following HPLC or immunofiltration purification. Urinary LTE4 was also measured
in healthy children (age 3-12) and found to be 103 +/- 9.
PMID- 9653770
TI - Expression of platelet-activating factor receptor transcript-2 is induced by
shear stress in HUVEC.
AB - Platelet-activating factor (PAF) is an important lipid involved in inflammation
reaction and circulation regulation. The receptor for human PAF is synthesized
from two spliced transcripts of the same gene. Our observation in the present
study shows that HUVEC express transcript-1 only in the static condition. Shear
stress induces the expression of transcript-2 in these cells but not transcript
1, resulting in increased PAF receptor expression as measured by FACS analysis.
These results suggest that shear stress may increase the susceptibility of
endothelial cells to PAF by inducing transcript-2 expression.
PMID- 9653771
TI - Cationic lipids (lipofectamine) and disturbance of cellular cholesterol and
sphingomyelin distribution modulates gamma-secretase activity within amyloid
precursor protein in vitro.
AB - To study beta-amyloid protein generation we expressed different amyloid precursor
protein (APP) isoforms in the human neuroblastoma cell line SY5Y (for details see
(1)). Treatment with lipofectamine, an cationic lipid for eucaryotic cell
transfection, inhibits gamma-secretase activity and stimulates the physiological
APP cleavage by alpha-secretase activity. Beside the MDL inhibitor (2), this is
the second agent that shows modulation of gamma-secretase activity in vitro.
Further, we show that disturbance of cellular cholesterol and sphingomyelin
distribution in transfected SY5Y cells results in an overproduction of beta
amyloid protein. This provides experimental evidence that membrane instability
influenced the proteolytic activity of gamma-secretase within the APP molecule.
PMID- 9653772
TI - Differing profiles of prostaglandin formation inhibition between selective
prostaglandin H synthase-2 inhibitors and conventional NSAIDs in inflammatory and
non-inflammatory sites of the rat.
AB - The present study examined the inhibitory profiles of NS-398 and nimesulide
against prostaglandin (PG) formation in inflammatory and non-inflammatory sites,
and compared them with those of aspirin and indomethacin. In vitro, indomethacin
inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and
nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg)
slowed the rate of plasma exudation and thus the exudate accumulation in rat
carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg)
also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than
TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did
not exhibit this selectivity. The levels of PGE2 correlated significantly with
the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2
formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10
mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory
profiles from aspirin and indomethacin against PG formation. These results
suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may
play a more prominent role than PGI2 in plasma exudation.
PMID- 9653773
TI - Effects of luteinizing hormone (LH), PGE2, 8-Epi-PGE1, 8-Epi-PGF2 alpha,
trichosanthin and pregnancy specific protein B (PSPB) on secretion of
prostaglandin (PG) E (PGE) or F2 alpha (PGF2 alpha) in vitro by corpora lutea
(CL) from nonpregnant and pregnant cows.
AB - Both Day 14 corpora lutea (CL) of the estrous cycle and Day 200 CL of pregnancy
secrete detectable prostaglandin E (PGE) and prostaglandin F2 alpha (PGF2 alpha)
in vitro. Corpora lutea from Day 200 pregnant cows secrete more PGE and PGF alpha
in vitro than Day 14 CL of the estrous cycle when incubated in control medium
without treatments (p < or = 0.05). In addition, secretion of both PGE and PGF2
alpha in vitro by both Day 200 CL of pregnancy and Day 14 of the estrous cycle
increase (p < or = 0.05) with time in culture in the absence of treatments. The
PGE:PGF2 alpha ratio secreted at 4 h in the absence of treatments by Day 14 CL of
the estrous cycle was 1.2 and at 8 h was 1.0 and did not differ (p > or = 0.05),
while the PGE:PGF2 alpha ratio secreted by 200 day CL of pregnancy in the absence
of treatments at 4 h was 0.8 and at 8 h decreased (p < or = 0.05) to 0.4. The
PGE:PGF2 alpha ratio at 8 h by 200 day CL of pregnancy was lower (p < or = 0.05)
than in the Day 14 CL of the estrous cycle at 4 or 8 h. Secretion of PGE or PGF2
alpha was affected by luteinizing hormone, PGE2, 8-Epi-PGE1, 8-Epi-PGE2,
trichosanthin, and pregnancy specific protein B (PSPB) and was time and dose
dependent (p < or = 0.05). In summary, the altered ratio of PGE:PGF2 alpha may
explain the decreased secretion of progesterone at 8 h by Day 200 CL of pregnancy
reported previously from the same samples. In addition, caution should be
exercised in interpretation of progesterone secretion data with bovine CL studies
in vitro. Also, PSPB may play an indirect role through PGE to regulate bovine
luteal secretion of progesterone.
PMID- 9653774
TI - Inhibition of Na+,K(+)-ATPase by platelet-activating factor in dog submandibular
glands.
AB - Physiological stimulation of dog submandibular gland has been shown to generate
platelet-activating factor (PAF). However, PAF is not released from cells in the
tissue. To assess its intracellular activity, the effect of PAF on Na+,K(+)
ATPase was examined in dog submandibular gland cells. PAF inhibited Na+,K(+)
ATPase in membrane preparations, and the inhibitory effect was dependent on the
protein concentration in the enzyme preparation. The inhibitory effect of a low
concentration of PAF was antagonized by a PAF-receptor antagonist, BN 50,739, but
at high concentrations, PAF was not antagonized. Kinetic analysis of PAF
inhibition of Na+,K(+)-ATPase suggests that the inhibition of Na+,K(+)-ATPase by
PAF is not due to competition by PAF at K(+)- or Na(+)-binding sites on the
enzyme, but by complex inhibitory mechanisms. These results suggest that PAF may
interact with specific and nonspecific site of action resulting in the inhibition
of Na+,K(+)-ATPase. Ouabain increased mucin release from dog submandibular gland
cells. Because Na+,K(+)-ATPase and ion exchange pathways are important in the
secretory responses of acinar cells, PAF may regulate intracellularly the
secretory function of acinar cells by modulating Na+,K(+)-ATPase and ionic
homeostasis.
PMID- 9653775
TI - Prostanoid-induced contraction of the rabbit isolated uterus is mediated by FP
receptors.
AB - Natural and synthetic prostanoid agonists were used to study the prostanoid
receptors involved in contraction of the mature, isolated uterus of virgin
rabbits. The prostanoids elicited contractile responses with a rank order of
potency of PGF2 alpha, fluprostenol > PGD2 > U-46,619 > PGE2 > carbaprostacyclin
with mean EC50 (nM) values of 4, 6, 34, 550, 1318 and > 10,000, respectively.
Carbachol, a muscarinic agonist given after the prostanoids to elicit a reference
contraction, had a mean EC50 value of 1.1 microM. The results show that the
mature rabbit uterus is most sensitive to prostaglandin FP agonists and, thus,
can be defined pharmacologically as an FP receptor preparation. These findings
may facilitative investigations into the possibility of different prostanoid
receptor populations. In the absence of useful competitive FP receptor
antagonists, agonist potency data is particularly useful in systems where cross
species comparisons and tissue-related factors are not involved. The potent
activities of the FP agonists, PGF2 alpha and fluprostenol, in the isolated
jugular vein and uterus of the rabbit suggest that these tissues may be useful
for intra-species comparisons.
PMID- 9653776
TI - [Computer-assisted psychiatric rehabilitation].
PMID- 9653777
TI - [Effectiveness of computer-assisted attention training of schizophrenic
patients].
AB - Recent years witnessed a considerable proliferation of computer-based training
programmes as instruments of cognitive rehabilitation for schizophrenic patients.
A study on the effects of a 3-week computer-based attention training with
schizophrenic patients is presented. The Span of Apprehension and the Continuous
Performance Test (CTP) were carried out before and after the training period.
Performance improvements were found only on few attention training tasks.
Schizophrenics had higher post-treatment hit rates on the Span of Apprehension,
but no post-treatment improvements were observed in the CPT. Performance of
trained patients in the external attention measures was not superior to
performance of matched schizophrenic control patients. These data suggest that
brief intensive computer-based attention remediation does not lead to enhanced
attentional capacity in schizophrenia. Thus, it might be more adequate to teach
behavioural strategies that bypass attention deficits or to offer programmes for
exercising more complex cognitive skills than to try to remedy basic cognitive
impairments.
PMID- 9653778
TI - [Computer-assisted cognitive training of schizophrenic patients. Use of
evaluation outcome for developing an individualized training method].
AB - The paper deals with the evaluation of a computer-based cognitive group training
programme for schizophrenic patients. The evaluation of the training results of
100 patients who participated in an earlier training scheme showed ceiling
effects in up to 46% of the cases. In the remaining cases the improvements varied
in a wide range between 1.6 and 20%. These results implied that the training had
to be adapted more closely to the specific needs of the individual patient. To
this end we developed criteria for each task to decide whether training in this
task is necessary or the performance is sufficient. This approach limits training
to those tasks in which patients display deficits. Satisfactory improvement
terminating training for the specific task, is defined as an increase in correct
responses of at least 10%. For those tasks in which reaction times are used as
performance measure, the criterion is a 10% increase in percentile rank. An
analysis of the new training programme with the data of 20 patients revealed that
27% of the tasks showed ceiling performance with no further training need. In the
remaining tasks the patients' performance attained the training criterion in 68%,
at instances mostly even after one additional session. These preliminary results
indicate that the new training scheme is able to provide more flexibility,
individualization and an enhanced focus on the patients' deficits.
PMID- 9653779
TI - [Computer-assisted neuropsychological training in neurological rehabilitation].
AB - Using computer-assisted cognitive training to treat patients with cognitive
disorders has proved a useful tool in neurological rehabilitation. This has been
shown by positive experience in many rehabilitation clinics but also in numerous
control studies investigating the efficiency of such training. Patients with
attention deficits show the most pronounced improvements as the computer with its
technical possibilities is an ideal training instrument because of stimulus
representation and reaction time measures. In other areas, computer training has
become an essential therapeutic means complementing other therapies. In a
clinical environment it seems that computer training is essential because it
enables attaining the necessary therapeutic density. However, training must be
integrated and become part of a global therapeutic framework.
PMID- 9653780
TI - [Computer-assisted training in genetically-induced neuropsychological deficits. A
case report of a patient with de Grouchy syndrome I (chromosome 18 p syndrome)].
AB - The present case study is a report on computer-based training approach in a male
patient suffering from the de-Grouchy syndrome I (with a characteristic
chromosomal deletion pattern), who along with psychotic symptoms displayed
neuropsychological deficits. Participating in a well-established intervention
programme aimed at a broad spectrum of psychological functions, the patient went
through 36 training sessions. With regard to outcome assessments one focus was on
improved performance in the training tasks, while the other one referred to
transfer effects, as indexed by a neuropsychological test battery which was given
before and after the entire programme. In both areas substantial gains from
training emerged according to the collected data. In view of these results
neuropsychological training approaches appear to have a perspective even in
behavioural deficits with a genetic basis.
PMID- 9653781
TI - [Psychotropic drugs in pregnancy: uses and risks].
AB - To reduce insecurities concerning the pros and cons of psychopharmacological
treatment of mental disorders during pregnancy, recent papers on teratogenic
risks of different (groups of) drugs, and on therapeutic strategies of psychiatry
disorders were reviewed and the results summarised. Psychotropic medication
sometimes increases the risk of congenital malformations. It may cause peripartal
toxicity and neurobehavioral changes; on the other hand, these risks have to be
weighted against the proven benefits of the drugs. Untreated mental disorders
seriously endanger the offspring during pregnancy and after delivery, and hence
psychopharmacological treatment may be advisable in spite of the risks involved.
PMID- 9653782
TI - [Children of mentally ill parents. A study of problem awareness in clinical
routine practice].
AB - The risk of developing clinically relevant psychiatric disorders in the lifetime
course is significantly greater among children of mentally ill parents. A child
adapted programme of information concerning the nature and symptomatology of
parental illness is considered to be an important preventive factor, and lies
within the domain of the psychiatrist's or therapist's responsibilities. During
the developmental phase of a prevention project at Freiburg University's
Department of Psychiatry and Psychotherapy, both clinical practice and the level
of problem awareness among patients and the therapists were evaluated. Over a
period of one year, consecutive interviews involving 114 patients with children
under 18 years of age, as well as their respective therapists, were conducted.
The results showed that: scarcely any exchanges between children and therapists
took place; the extent to which children are informed about parental illness must
be considered as small; a high percentage of such children are already evaluated
by their parents as disturbed, and the pressing need for support exists.
PMID- 9653783
TI - [Suicide in depression, lost years of life and gross social consequences. What is
the outcome of suicide prevention?].
AB - In recent years there has been a tendency in research and clinical treatment to
discuss also economic aspects of mental illness in the context of outcome and
consequences of treatment for the individual and society. In our study on
economic consequences of suicide prevention we could show that a reduction of
suicide mortality of depressed patients could save money to the tune of thousands
of million Deutschmark.
PMID- 9653784
TI - [Interviewer effects in assessing subjective quality of life and satisfaction
with care in sheltered housing].
AB - The impact of interviewer-effects on subjective evaluative criteria was examined
in a randomized control group design (n = 26 x 2) of clients of sheltered living
in Berlin-Spandau. The assessment of care and subjective quality of life showed
that clients were more satisfied if they had been interviewed by their
responsible caregivers compared to interviewers from other providers of the same
region--unknown to the clients. Conductibility of interviews was independent of
interview conditions. A systematic overestimation of satisfaction should be taken
into account if responsible caregivers interview their own clients. Such data
should not be used comparing different settings.
PMID- 9653785
TI - [Patient suitability for discharge from psychiatric hospitals].
AB - OBJECTIVE: To assess the possibility of discharging psychiatric inpatients of two
large Mental Hospitals in Lower Austria. METHODS: A point prevalence study was
performed in 1992. Treating psychiatrists were asked to evaluate the possibility
to discharge patients under the hypothetical assumption that a broad range of
residential facilities were available. RESULTS: The inpatient proportion had
decreased from 2179 in 1974 to 1032 in 1992. Of the 1992 population 75.7% might
be discharged. Most patients (41.5%) were regarded as needing a permanently
staffed home. CONCLUSIONS: Although the inpopulation of the two large Mental
Hospitals studied had decreased over a period of 18 years already by over 50
percent, the results of this study show that there is a large potential for
further reform. Since the evaluation was carried out by the treating
psychiatrists in the hospital, who might have been in a conflict of interests or
might have preferred the treatment they are providing themselves, this finding is
particularly remarkable.
PMID- 9653786
TI - [Ecstasy and social pension: lost for life at 20 years of age?--Behavioral
therapy of an anxiety disorder].
PMID- 9653787
TI - [Attempted suicide in Alzheimer phobia].
PMID- 9653788
TI - [The right for care does protect: a case].
PMID- 9653790
TI - [Facial-oral therapy in craniocerebral diseases].
AB - Presented are 16 patients (4 women and 12 men) of a neurological early
rehabilitation ward with various neurological initial situations. Diagnoses range
from traumatic brain damages to hypoxic brain lesions caused by complications
during anaesthesia, from subarachnoid haemorrhages with consecutive
complications, to intracerebral haemorrhages. All patients have been examined at
the beginning by an ENT specialist and/or phoniatrically. Regarding the structure
of the patients' complex neurological symptoms, they were all suffering from more
or less severe impairments in the faciooral tract. At the beginning of the
multifocal neurological rehabilitation treatment all patients had been submitted
to dysarthrophony and/or dysphagia examination according to K. Coombes. We will
compare results, objectives and therapeutic developments during the faciooral
therapy including physiotherapy and ergotherapy based on the Bobath concept. We
will further discuss the periods between occurrence of the damaging event and the
onset of multimodular neurological rehabilitation. Further discussed is the
influence of secondary complications on the therapeutic development and, finally,
the clinical-social outcome of the patients.
PMID- 9653791
TI - [The significance of urinary tract infections in patients with cerebrovascular
diseases during clinical rehabilitation].
AB - In 361 patients with cerebral stroke a study of medical and neurological
complications was undertaken. Among a total of 131 complications (36.2%) a
striking incidence of urinary tract infections was seen: 83 cases (22.9%).
Patients without complications had an average stay of 61.2 days in hospital,
those with urinary tract infections had 77 days (p < 0.05). In patients with
cerebrovascular accidents voiding dysfunctions are common. Great care must be
taken to prevent complications: indwelling catheters should be used only over
short periods of time. In case urinary drainage is needed over a long period of
time, suprapubic catheterization should be preferred.
PMID- 9653792
TI - [Future occupational plans of patients after orthopedic rehabilitation: how are
they expressed? What influences them?].
AB - Perceptions about one's occupational future are regarded as the initial phase in
an ongoing process of occupational resettlement towards achieving gainful
activity. Actual gainful activity, however, tends to be increasingly dependent on
a number of labour market variables. At the end of an orthopaedic rehabilitation
measure, 341 patients with pain syndromes of the locomotor system were
interviewed concerning their vocational perspectives and notions, and the data
obtained were studied in association with anamnestic and psychosocial factors. It
is assumed that both plain expectations (such as returning, or not returning, to
work) and multi-layered statements alike (such as the dual message of returning
and of not returning to work, at first glance incompatible) will frequently be
masked in the interview. Distinct, differing patterns were nevertheless found for
the various patient groups regarding pain description, pain course, subjective
disablement by pain, subjective job burden, subjective well-being, rehab
expectations, and judgement of therapy outcome. Similar differences were stated
for the social situation, indicated inter alia by (in)capacity for work, or
application for benefit award (severely disabled person status, invalidity
pension). Pain drawings, pain severity scaling, differentiated description of
various pain qualities, the Pain Disability Index, all emerged as useful and
practical additional tools in elucidating these patterns.
PMID- 9653793
TI - [Reliability and validity studies with the triflexometer, a new method for
assessing form and flexibility of the spine].
AB - Developed by Orthotronic Medizintechnik GmbH, the so-called Triflexometer,
version 3.22 was tested for its reliability and validity in measuring spinal
posture and mobility. Reliability studies on 20 healthy subjects have shown this
measurement method to be reliable, yet intra- and inter-rater reliability
analyses also revealed that even for this healthy population discrepancies in the
various measures may occur, both due to differences in compliance as well as
fatigue and learning effects, and due to difficulties in stabilization of the
normal posture, to a lesser extent due to certain specifics of the measurement
technique (placing the markers, guiding the sensor). In total spinal immobility
(ankylosing spondylitis), practically identical measurements are found, as is the
case in dummy studies. The validity study on 20 healthy subjects found good
correlations between the measurements obtaining using the triflexometer and those
for double inclinometer, respectively, and that only minor mean value differences
occur for the two methods. Also, triflexometer measurements for total anteflexion
were found to correlate with those determined with the fingertip-to-floor method,
no correlation was present however between the Triflexometer values and the
Schober test. Triflexometer measurements performed on 114 healthy subjects of
various ages served to prove that the range of spinal movement in the directions
measured (sagittal and frontal) will reduce with age. To a lesser extent, this
also applies to hip movement. Overall, our findings prove the triflexometer an
easy-to-handle system which possesses high reliability and is suitable for valid
and objective noninvasive assessment of global and segmental spinal mobility.
Triflexometer examinations are highly uncomplicated to implement, and print-outs
of the results obtained permit lasting documentation of the present status.
PMID- 9653794
TI - [Integrated occupational work capacity evaluation in medical rehabilitation-
experiences and prospects exemplified by psychosomatic rehabilitation].
AB - Psychosomatic rehabilitation is often initiated when lasting work disability,
loss of job, and pension application have occurred. After a review of the
relevance of vocational strains and of predictors for reintegration, we present a
model of an integrated work hardening programme in Psychosomatic Rehabilitation.
Results for 64 patients are illustrated by case vignettes. Especially when
lasting work disability and unemployment have undermined the patients' sense of
competence and endurance, work hardening promotes return to work, realistic self
appraisal and vocational reorientation. The social and medical assessment and the
coordination of vocational rehabilitation measures are improved. The
implementation of a work hardening programme requires the provision of a variety
of (unpaid) work opportunities, independent assessment of work performance by
supervisors and social worker, psychological support and close cooperation with
rehabilitation services.
PMID- 9653795
TI - [Identification of psychologically impaired patients in cardiologic
rehabilitation].
AB - As psychological factors have a substantial influence on the further medical,
psychological and occupational career of a patient with somatic disease, early
identification of patients with psychological disturbances is of special
importance in medical rehabilitation. The share of psychologically disturbed
patients in a cardiac rehabilitation clinic has been screened. Different methods
for identification of anxious and depressive patients (by medical and
psychological staff as well as a screening instrument) are compared. Concluding,
the benefit of introducing a screening instrument as a routine procedure is
discussed under the aspect of effectivity.
PMID- 9653796
TI - [Community occupational rehabilitation for women--a model project of Frankfurt am
Main vocational guidance in Kassel].
PMID- 9653797
TI - [Quality assurance in early neurological/neurosurgical rehabilitation. Federal
Working Group of Medical-Occupational Rehabilitation Centers (phase II)--Working
Group for Early Neurologic/Neurosurgical Rehabilitation].
PMID- 9653798
TI - [Measuring the quality of life of children and adolescents with asthma--The
Pediatric Asthma Quality of Life Questionnaire].
AB - Quality of life becomes more and more important in evaluating the effects of
treatments. At the moment, different questionnaires to measure quality of life in
children and adolescents with asthma are available. The Paediatric Asthma Quality
of Life Questionnaire (PAQL) was developed by Juniper and co-workers in Canada
and has already been translated into German. It is a self- or interviewer
administered instrument for children and adolescents between age 7 and 17. The
PAQL contains 23 items in three domains: activity limitation, symptoms, and
emotional function. The empirical results suggest that the PAQL is reliable and
sensitive to clinical change. Problems associated with the administration are
discussed.
PMID- 9653799
TI - References to people in the communications of female and male youths with mental
retardation.
AB - Gender-related differences have consistently been reported in the language of
adults and children with no disabilities. One well-replicated finding is that
females discuss people and relationships more often than do males, particularly
in conversations with other females. These stylistic variations in language are
considered to have implications for the adaptive functioning of language users,
most particularly females. Although studied thus far only in nondisabled
individuals, such issues of language style use may be of equal or greater concern
for those with mental retardation. How does a cognitive impairment intensify or
reduce gender-linked language styles and their effects? Language transcripts were
obtained from eight male and eight female participants with retardation,
interacting separately with one male and one female adult partner. Half of the
participants used speech as their primary mode of communication: the others
relied on vocalization, gesture, or augmented modes. Participants using speech
showed gender-linked language patterns similar to nondisabled individuals, with
females discussing people significantly more often than males. Females using
nonspeech modes, in contrast, showed a severe reduction in person-referencing
that was not accountable by their expressive speech limitations.
PMID- 9653800
TI - Implementation and effectiveness of a home-based early intervention program for
blind infants and preschoolers.
AB - This article presents results from a comprehensive evaluation of a home-based
early intervention project for congenitally blind young children. Five full-term
and five preterm blind children, who had a mean age of 12 months at the beginning
of the project, were visited at home with their families every 2 weeks over a 2
year period. Results showed that an individualized, handicap-specific early
intervention using different types of parent involvement (cotherapist, parent
counseling) could be implemented successfully. Compared with controls,
developmental test data from the ages of 12 to 36 months showed an accelerating
impact on the full-term children. However, no intervention effects could be found
in the preterm children. This finding was mainly due to methodological
limitations (e.g., selection bias). The best results among full-term children
were found on blindness-specific scales (e.g., orientation and mobility). It is
concluded that the outcomes in full-term children confirm the success of this
type of early intervention.
PMID- 9653801
TI - Perception of service needs by parents with intellectual disability, their
significant others and their service workers.
AB - It is well recognized in the literature that parents with intellectual disability
require support and social services. There is growing interest in these services
being responsive to parent-identified concerns, particularly as it has been
suggested that parents' concerns may differ from those reported by service
workers, family members, or friends. In the Australian study reported here, the
views of parents with intellectual disability, their significant others and
service workers were sought on parents' service needs on 20 items incorporating
child care, social and community living, and domestic skills. There were
significant differences in the perceptions of the parents, workers, and
significant others on the help parents needed. Several gaps in services were also
identified. From the parents' perspective, their greatest unmet needs were in the
community participation area, specifically with help to explore work options, to
know what community services are available and how to access these, and to meet
people and make friends.
PMID- 9653802
TI - Resident behaviors and characteristics as determinants of quality of residential
care: an observational study.
AB - The effects of resident behaviors and resident characteristics on the quantity
and quality of care they receive from direct-care staff was examined. Four
hundred and fifty-two residents with severe and profound mental retardation and
416 direct care staff members were involved. Naturalistic observations were
conducted on direct-care staff behavior, that is, staff-resident initiatives,
staff affection, staff communicative behavior, on resident behaviors (i.e.,
maladaptive, stereotypic, and adaptive behavior, position, attending, and
communicative behavior), and on resident characteristics (i.e., gender, age,
ambulancy, sensory handicaps, and seizure disorder). By importance, residents'
ambulancy/motoric skills, their communicative behavior, and attending behavior
accounted for the greatest differences in the quality and quantity of the care
they receive from direct-care staff. Given that certain resident characteristics
can be ameliorated through training, residents themselves may control, to a
certain extent, the care they receive from direct-care staff in residential
facilities.
PMID- 9653803
TI - Attention deficit hyperactivity disorder among adults with severe and profound
mental retardation.
AB - The present study investigated the incidence of attention deficit hyperactivity
disorder in a sample of 86 adults with severe to profound mental retardation.
Participants were evaluated by supervisory staff using the diagnostic criteria
from the Diagnostic and Statistical Manual of Mental Disorders (American
Psychiatric Association, 1994) and Conners' (1990) Hyperactivity Index. Using the
most conservative measure, 15% of the sample met the diagnostic criteria. This
measure was not influenced by the subjects' chronological age, adaptive age, IQ,
or gender. Implications of this finding for continued research and practice were
discussed.
PMID- 9653804
TI - The effects of biological and social risk factors on special education placement:
birth weight and maternal education as an example.
AB - The effects of birth weight (BW) and maternal education (ME) on special education
placement at age 10 were studied. Epidemiologic methods quantified risk to the
individual and to the population using an electronically linked, county-wide
database of birth and school records. A dose-response relationship was found
between BW and ME. High ME may serve as a buffer for children with a biological
risk for developmental delays. A clinically important finding was that children
born with very low BW to mothers with low ME were at a high level of individual
risk for receiving special education services. However, such children accounted
for a small number of the overall cases. The largest percentage of children
receiving special education services had the single risk factor of low ME. From a
public policy standpoint, children born to mothers with low levels of education
are an important group to target for early intervention.
PMID- 9653805
TI - The sources of variation in the human genome and genome instability in human
cancers.
AB - The human genome is viewed as a stable collection of about 60,000-70,000 genes--a
minority of protein--coding DNA sequences--dispersed in a large majority of
noncoding DNA sequences--more than 90 per cent of the entire genome sequences.
Some of these ubiquitous noncoding DNA sequences, metonymically called "parasitic
DNA," "ballast DNA," "selfish DNA" or "extra DNA," especially, the repeated
sequences tandemly organized, are not stable but vary with considerable
frequency. Recently, the confused or inadequately known origin of native of
pathological variations of these DNA sequences appears to be unravelled, with
great implications in genome stability. The human chromosomes, the bearer of
genome, store and carry it. Their structure is qualified to perform its
fastidious functions. The chromosomal conformation, "with variable geometry,"
exposed to genetoxic action of different damaging factors and to torsional stress
after their fast and repeated changes during mitosis. The exaggerate exceeding of
the native variation of human genome in disease states, probably, generates
genome instability. The chromosome fragility--the cellular phenotypic expression
of these molecular instability--reflects the closely relations between the genome
and its carrier. The pattern of DNA replication with asynchrony of different
domains of "parcelled" genome and the results of replication, susceptible to be
corrected by the action of DNA repair genes, render certain limited regions of
genome more vulnerable to damaging. These "target" regions focused damaging
effects and exhibit an increased susceptibility to breakage and recombination,
often with chromosomal expression. The coincidence of these regions, frequently,
with locations of many protooncogenes and sometimes, antioncogenes could be
subsequently, starting points for a genuine chain of genomic events related to
growth cell and cell division. Cancer multistage accumulation of various genomic
disorders in a single cell tends to take advantage of discriminating situations
of these regions, which themselves can generate other genetic disorders,
involving its in carcinogenesis. The gene expression disorders or the genuine
mutations of dominant protooncogenes and the recessive behaviour of antioncogenes
explain the nature of human cancers--a mixture of inherited and somatically
acquired gene disorders. They attest the recessive characteristic of human cell
malignancy and emphasize the decisive role of cancer predisposition which
operates in interaction with damaging environmental factors. Seemingly, the
pivotal causes of genome instability originate from strange behaviour of certain
repeated DNA sequences dispersed throughout the human genome. Perhaps they hold
the key to the puzzle of cancer processes.
PMID- 9653806
TI - Possible involvement of L-arginine-nitric oxide pathway in the modulation of
stress-induced analgesia.
AB - The possible participation of NO in the pain modulation and stress analgesia was
studied in Wistar adult rats. Cerebral citruline as a stoichiometric coproduct of
NO from L-arginine increased from the mean value 5.6 +/- 0.4 nM/mg.Pt. to 8.9 +/-
0.5 nM/mg.Pt. in acute immobilization stress. Intraperitoneal administration of L
arginine caused only in high doses (50 mg/kg body weight) a small transient
decrease of tail-flick latencies to the thermoalgesic stimulus, without
significant changes of the stress analgesia induced by the restraint stress. In
the pretreated animals with L-NAME a progressive increase of latency time was
obtained and the increased latencies induced by acute immobilization appeared
significantly potentiated. These results offer new indirect evidence in favour of
the modulatory role of NO in the thermoalgesic sensitivity and stress induced
analgesia.
PMID- 9653807
TI - The renin-angiotensin system and the effect of propranolol upon the cerebral
cortical and hypothalamic circulation in hypoxia.
AB - The regulatory mechanisms of the cerebral blood flow have preoccupied the
physiology department of Cluj since the end of the 4th decade. These studies
continued over the last years. The researches progressed from the studies of
regulation by blood pressure changes to the nervous regulation and to the
metabolic one. This paper's subject is the renin-angiotensin and adrenalin system
influence on the changes of cerebral blood flow during the general hypoxic
hypoxia and cephalic ischemia. Experiments were performed in 10 dogs
anaesthetised with a mixture of chloralose, urethan and morphine. Hypoxic hypoxia
was obtained by breathing a mixture of 11% oxygen in nitrogen, in a closed system
and cerebral ischemic hypoxia by partial compression of the carotid arteries,
after the ligation of the vertebral and thyroid arteries. The arterial blood
pressure and the cerebral and hypothalamic blood flow, measured with the heated
thermoelement, were registered. The plasma renin activity was tested
radioimmunologically before, at 1.5 min, 5, 10 and 15 min, after the beginning of
hypoxia. In ischemic hypoxia the experiment was repeated after venous perfusion
with propranolol (0.6 mg/kg/h). The systemic blood pressure increased in both
forms of hypoxia. The cortical and hypothalamic blood flow increased with the
systemic arterial blood pressure. The hypothalamic blood flow remained stable or
diminished a little. Propranolol increased the cerebral blood flow during
ischemic hypoxia up to 300%. The i.v. administration of angiotensin (1-5 mg/kg)
increased the cortical flow, while the hypothalamic flow remained self-regulated.
Plasma renin activity increased more in general hypoxic hypoxia, than in cephalic
ischemic hypoxia. After propranolol the increase was higher in this hypoxia.
Propranolol produced a major activation of the renin-angiotensin system and of
the cortical blood flow in ischemic cephalic hypoxia, the renin-angiotensin
system being located in the cerebral structure. As well high doses of angiotensin
produced cerebral vasodilatation in small cerebral vessels. This effect was found
in our experiments in the cortical blood flow too. Our results indicate a
beneficial propranolol effect on cortical circulation in ischemic hypoxia.
PMID- 9653808
TI - Heart ultrastructure in experimental acute pancreatitis.
AB - Acute pancreatitis reproduced on white rats provoked following modifications of
myocardium ultrastructure: 1. Affection of the microcirculation vessels
structure, what induce interstitial edema and cardiomyocytes hypoxia. 2. The
cells appearance of a rough type with the overcontracted myofibrils making up,
probably occurs as a result of supercharging with calcium can be caused by
deficiencies in the sarcolemma structure. 3. The intracellular edema of the
cardiomyocytes and their supercharging with calcium can be caused by deficiencies
in the sarcoma structure. 4. In the latest periods, the cardiomyocytes and the
connective tissue reactions to the lesion is represented of compensatory
hypertrophy of the cardiomyocytes and collagenizing the myocardium stroma.
PMID- 9653809
TI - O.H.--a strong slow wave sleep inducing factor in tortoise (Emys orbicularis).
AB - The paper would be a contribution to the very complex and not yet clarified field
of neurochemistry of slow wave sleep (SWS). The study was performed on 30
tortoises (Emys orbicularis): 20 "donors" and 10 "receivers". The animals were
equipped with chronic cannula inserted in the third ventricular space and
electrodes for electrographic recording (EEG, EOG, EMG and ECG). The controls
consisted in administration into the third ventricle of receivers of 30
microliters of saline or concentrated cerebro-spinal fluid (CSF) extracts from
awake donors. The results were negative, i.e. the injected tortoises conserved
their waking state indefinitely. The experiments were performed by introduction
of 30 microliters of concentrated CSF extracts obtained from asleep donors into
the third ventricular space of receivers. All the animals presented the
behavioural and electrographic signs of the physiological SWS. The logical
conclusion is that in the development of reptilian SWS, an endogenous SWS
inducing factor, which I called "O.H." (orbicularis hormone), was secreted by
some hypnogenic structures and discharged in the CSF, with the consequences
presented above.
PMID- 9653810
TI - Visual processing of configuration-dependent spatial characteristics of shapes
and patterns. A model useful in the study of the role of the departure from
circularity or dispersion of shapes in human visual perception.
AB - In this work a theoretical model was used in combination with testings on normal
subjects to get more insight in the role of the departure from circularity or
dispersion of the shapes in visual perception. The model was inspired by the
observation that the intensity of the effect of a given level of contrast of a
shape usually increases, for the same area, with the shape being better
concentrated around a center. The model introduces as a measurable characteristic
the degree of concentration or dispersion of a shape with respect to a center.
The measure was based on the maximum of the convolution integral of the
characteristic function of the shape with the weighting function 1/2 pi r, r
being the distance between the point of convolution and the surface element to be
integrated. A program for the calculation of the degree of concentration of
figures and other related processing operations was developed in Turbo Pascal
language on a 486 PC. The program included the possibility to generate various
figures and to operate on them various transformations such as strangulation,
fragmentation with separation of fragments. The model introduces a center of the
figure, the point best surrounded by the whole figure, with a geometric and
visual significance, as resulting from the good concordance between its
calculated and perceived positioning in different relatively simple shapes. In
symmetrical compact figures subjected to a central separation or narrowing two
centres appear entering the two resulting nuclear parts; a good concordance
between model and perception was again observed in this transition to two centres
and their subsequent positions in the two nuclear parts. In accord to model
prediction, testings showed a very pronounced dependence of the summation
efficiency over a contrasting area on the degree of dispersion of the area. This
is reflected in the drastic decrease upon figure dispersion of the intensity with
which a given brightness or colour contrast is perceived. Thus, the model gives a
better explanation and a more efficient way to approach the great capacity of the
visual system to disclose more compact shapes or agglomeration zones in a complex
visual scene. This capacity is to a large extent due to the increase in the
intensity with which a given contrast is perceived, occurring in these
conditions. This intensity, which strongly depends on the degree of concentration
or dispersion of the figure, becomes an important additional signal leading to
the accentuation of the difference between compact and rarefied shapes. The model
based on the degree of concentration determined around a centre, although useful
for finding a centre and applicable satisfactorily to many shapes, do not cover
well all aspects of shape dispersions. In shapes without a dominant central part
the confrontation model-testing showed an important involvement in global
perception of all local concentrations, not only central but also peripheral, the
later underestimated in our model. The model can be however improved by taking
into account also such local concentrations.
PMID- 9653811
TI - Effects of electrolytic bilateral symmetric lesions of the arcuate nucleus on the
phagocytic activity and on the phagocytic response in rats.
AB - Previous researches of Cluj-Napoca laboratories of Physiology (Benetato, Baciu et
al., 1945, 1946, 1947) demonstrated that direct electrical stimulation of the
tubero-mammillary area in dogs increases, in the following hours, the blood
polymorphonuclears phagocytic activity. By contrast, electrical damage of the
same region produces a depression of the basal phagocytic activity and a blocking
of the phagocytic response (Baciu et al., 1958, 1988). In the present research we
assumed there is a stimulating effect of the arcuate nucleus, located in this
area, on the phagocytic activity of blood neutrophils. We used an anodal current
to stereotaxically induce lesion of the arcuate nucleus in six rats. A control
group of six animals was used. Five days later, phagocytic response was induced
with a Gram negative bacterial extract given i.v. The results demonstrated a
decrease of the phagocytic activity from 164.31 +/- 17 bacteria engulfed by 100
neutrophils in controls, to 138 +/- 12.8 in the lesioned group p < 0.05.
Phagocytic response after five hours appears depressed in the lesioned group (138
+/- 12.8 to 156.25 +/- 13.3, p < 0.05). Similar results were obtained after 24
hours. In control animals the response is very significant after 5 and 24 hrs.,
respectively, (p < 0.001). In conclusion, the arcuate nucleus is moderately
involved in sustaining the basal phagocytic activity of blood neutrophils. It has
an important role in phagocytic response.
PMID- 9653812
TI - Immunity and stress.
AB - The relationship between stress and immunity is not a hot topic of
psychoneuroimmunology. The review outlines the main aspects of these
interrelations; stress sensitive immunological markers, experimental research and
studies on humans which underline the prevailing immunosuppressive effects of
stress are discussed. A classification of stress-related diseases comprises
autoimmune, acute, psychosomatic and neuroendocrine diseases. Besides the
hypothalamopituitary-adrenocortical axis and the symparthoadrenal system, newer
information points to the role of cytokines, opioids and other mediators in the
complex mechanisms involved. Several data from the physiological laboratory in
Cluj are included. The final consideration outlines some unclarified aspects and
new research directions.
PMID- 9653813
TI - Effects of monosodium glutamate on blood neutrophils phagocytic activity and
phagocytic response in mice.
AB - Previous researches of our laboratories (1945, 1946, 1947) have shown that direct
electrical stimulation of the tubero-mammillary hypothalamic area in dogs
enhances the blood neutrophils phagocytic activity and the phagocytosis
exhibiting leukocytes percent. After electrolytic damage of the same area,
phagocytic activity decreases and phagocytic response is suppressed (1985, 1988).
In the present work, we performed in mice extensive chemical lesions of the
arcuate nucleus, by means of the neonatal treatment with monosodium glutamate
(MSG). The experiment was carried out on 23 new-born mice. 15 mice were injected
with MSG (G group), the other 8, serving as control group, received isotonic
saline solution (C group). The studied parameters were, in both groups, the
weight evolution of the animals, the blood neutrophils and lymphocytes percentual
variation and the neutrophils' phagocytic activity, tested in vitro, expressed
through the number of bacteria engulfed by 100 neutrophils and through the
phagocyting neutrophils percentage. Phagocytic activity was tested in whole
heparinised blood, against E. coli. Phagocytic response was elicited by i.p.
injecting 0.05 ml bacterial suspension and was tested four hours later. The
results show that the arcuate nucleus has little influence upon maintaining basal
phagocytic activity--that does not significantly decrease after its chemical
damage--, but plays a decisive role in triggering the phagocytic response. The
neonatal MSG treatment also determines a decrease of the blood lymphocytes
percentage and induces obesity in up to 30 days old mice pups.
PMID- 9653814
TI - Investigation of immune reactivity in alcoholism with hepatic disease of various
degrees.
AB - The clinical and experimental investigations of alcoholic liver disease, have
proved that hepatocytes injury is associated with immunologic abnormalities,
which can be one of the sources of these injuries. The acetaldehyde, the main
ethanol metabolite modify liver cytosolic proteins and form new antigens. Thus
acetaldehyde induces the synthesis of auto-antibodies. Some hypotheses maintain
the autoimmune pathogenesis of these diseases. Research was carried out on some
patient groups admitted in the alcohol addiction department of the Neurology and
Psychiatry hospital "Professor Gh. Marinescu". We have investigated the alcohol
depending individuals with various degrees of hepatic injuries. Four groups have
been studied: the control group, the alcohol depending patients without liver
disease, the patients with alcoholic hepatitis, the group with alcoholic
cirrhosis. In order to investigate the immunologic response the research has been
carried on, along the following lines: serum immunoglobulins level, serum C3
level, serum protein C reactive level by using IDR, serum circulating immune
complexes by Hakova method, auto-antibodies (antinuclear AAN, antimitochondria AM
and antismoothmuscle ASM) by using indirect immunofluorescence, T lymphocytes by
E rosetting and lymphocytes by direct immuno-fluorescence. Clinical and
experimental study of the alcoholic liver has shown that destruction of
hepatocytes is accompanied by several immunological events.
PMID- 9653815
TI - Effect of nifedipine on electrical activity of the brain in rat.
AB - Effect of calcium channel blocker nifedipine on the electrical activity of the
brain in anaesthetized rats was studied. The electoencephalographic signals were
registered on a computer as series of data and thereafter they were decomposed by
Fourier analysis in very narrow fields of frequency. The electrical activity of
the brain of the control rats was asymmetrical, with a more important activity in
the left brain hemisphere, particularly between 20-30 Hz when the electrical
activity of the brain was globally more important. The nifedipine increased the
electrical activity of the brain between 0.5-4 Hz and 20-30 Hz in a dose
dependent manner. The drug also increased the interhemispheric asymmetry. Some
possible explanations of these effects are analyzed.
PMID- 9653816
TI - Experimental research on the effect of calcium channel blockers nifedipine and
verapamil on the anxiety in mice.
AB - The anxiolytic effect of the calcium channel blockers nifedipine and verapamil
was tested in mice using two test: the conditioned suppression of the motility
test and the black and white box test. The nifedipine but not the verapamil, in
low doses (0.1 mg/kg b.w), proved anxiolytic effect and both nifedipine and
verapamil in high dose (1.6-2.5 mg/kg b.w) had anxiogenic properties. The
anxiogenic effect was correlated with the capacity of the drugs to block the
calcium channels and the anxiolytic effect of low doses of the nifedipine was
considered to be produced by opening these structures. These data were considered
important for a new future aboard of the treatment and pathophysiology of the
anxiety.
PMID- 9653817
TI - A spectrophotometric assay of folic acid concentrations in rats: correlations
with age and organ.
AB - Spectrophotometric assays have been used to determine FA concentration in tissue
homogenates from various organs (liver, kidneys, brain, spleen) in white rats;
these studies were undertaken to test the age--and organ--dependent variations of
FA concentrations in tissue homogenates. The results showed a marked decrease of
FA concentration in the adult group of rats when related to the young group, and
in the aged group when compared to the adults respectively. Analysing the
determined values of folates in tissue homogenates of various organs (in rats
belonging to the same group of age), the highest concentration has been found in
the liver homogenate, followed in decreasing order by kidneys and to a much
greater distance, by the brain and spleen.
PMID- 9653818
TI - [Gastrointestinal hemorrhage of unknown origin].
AB - Among 174 patients admitted for acute gastrointestinal bleeding the source of
bleeding remained undetermined in 19 (10.9%) despite standard diagnostic workup.
We show that an unknown source of acute gastrointestinal bleeding is not a risk
factor with regard to the in-hospital outcome: there was no difference in the
number of in-hospital days, of PRBC transfused or of surgical interventions; none
of these patients died. While patient characteristics regarding mean age and sex
distribution likewise did not differ, there was a significantly higher percentage
of patients on NSAIDs or oral anticoagulants among those whose source of bleeding
could not be found (80 vs 42%; p = 0.002). The clinical follow-up of the patients
with undetermined source of bleeding reveals gastrointestinal pathology in a
considerable proportion (18%); it calls for close follow-up of these patients
after discharge.
PMID- 9653819
TI - [Autoimmune hepatitis in Switzerland].
AB - The incidence and course of autoimmune hepatitis in Switzerland are unknown. In
an attempt to obtain an overview of all patients at present under treatment in
Switzerland for autoimmune hepatitis, we circulated a questionnaire to all Swiss
gastroenterologists. Eighteen patients were identified and their symptoms, course
and treatment were evaluated. The majority were females, usually without liver
cirrhosis at the time of diagnosis. The course of the disease was largely
favourable.
PMID- 9653820
TI - [Hemosuccus pancreaticus: a rare cause of upper gastrointestinal hemorrhage].
AB - We report on a patient with alcoholic chronic pancreatitis and intermittent upper
gastrointestinal haemorrhage. Old blood was seen in the duodenum but no bleeding
source could be identified by endoscopy. Computed tomography scanner and
angiography disclosed an arterial pseudoaneurysm of the pancreatic tail, and left
splenopancreatectomy was performed. In cases of upper gastrointestinal
haemorrhage, the pancreas should be considered as a bleeding source if
endoscopies remain negative and the patient presents with chronic pancreatitis.
PMID- 9653821
TI - [Long-term follow-up of 9 islets of Langerhans autografts after resection of the
pancreas].
AB - INTRODUCTION: Preservation of physiological endocrine pancreatic function
represents a major problem in pancreatectomised patients. In 40 to 100%,
pancreatic resection can result in diabetes, which is often difficult to manage.
Islet autotransplantation has been proposed to prevent this severe metabolic
consequence. PATIENTS AND METHODS: Between March 1992 and January 1997 we
performed 9 human islet autotransplantations in Geneva. The patients comprised 6
males and 3 females aged 40 to 81 years (median: 51 years). The pancreatectomy
was total in 3 cases, subtotal (95%) in 2 cases and partial (40-80%) in the
others. Indications for resection were alcohol-induced chronic pancreatitis (6
cases) and focal benign pancreatic pathologies (3 cases). After collagenase
digestion, unpurified islets were injected intraportally and embolised into the
liver. Patient metabolic status was regularly tested by 24-hour serum glucose
profile, measurement of glycosylated haemoglobin, oral and intravenous glucose
tolerance tests and glucagon stimulation test. RESULTS: Immediately after
autotransplantation, one patient had persistent insulin-dependent diabetes. Among
the 8 patients who were insulin-independent soon after the graft, 4 presented a
progressive deterioration of endocrine pancreatic function and required insulin
therapy 5, 8, 24 and 36 months after the graft. Currently, 4 patients are insulin
independent: three of them have normal glucose tolerance tests (24, and 48 months
after the graft) and the last presented with glucose intolerance 22 months after
the graft but still does not require exogenous insulin. CONCLUSION: Islet
autotransplantation can be considered a useful therapeutic option serving to
prevent or delay the occurrence of surgically-induced diabetes. In our opinion,
islet autotransplantation should be offered to any non diabetic patient needing
to undergo major pancreatic resection.
PMID- 9653822
TI - [Isolation of the pig islets of Langerhans: evaluation of in vitro and in vivo
function].
AB - Pig islets are considered the best alternative to human islets in the treatment
of insulin-dependent diabetes. Pigs could represent a potential islet donor for
xenotransplantation in humans because of the close similarity between human and
porcine insulin and the theoretically unlimited availability of porcine pancreas.
From November 1991 to January 1997 we performed 221 pig islet isolations from 3
pig sources: group 1: minipigs (age 9-18 months) and white pigs (3-8 months),
group 2: large white pigs (5-8 months), group 3: large white pigs (12-24 months).
Islets were isolated according to a semi-automated method using enzymatic
digestion and purification through discontinuous Euro-Ficoll gradients. The
pancreases were surgically removed in our laboratory for group 1, while
pancreases from groups 2 and 3 were removed at the slaughterhouse with an average
warm ischemia time of 15 minutes. In vitro islet function was assessed by static
incubations and perifusions, and in vivo islet function by transplantation under
the kidney capsule of nude diabetic mice. The results were as follows: [table:
see text] Insulin secretion increased twofold after in vitro glucose stimulation.
We obtained restoration of euglycemia in diabetic mice which survived > 3 months
after the graft and returned to diabetes after nephrectomy. This study shows that
our isolated pig islets are viable and functional in vitro and in vivo after
transplantation.
PMID- 9653823
TI - [Splenic vein thrombosis and chronic pancreatitis: therapeutic approach].
AB - 10% of chronic pancreatitis (CP) cases are complicated by splenic vein thrombosis
(SVT) which is responsible for upper digestive haemorrhages. To improve our
approach to treatment we reviewed 30 cases of SVT associated with CP treated in
our centre from 1985 to 1995. 14 patients were treated conservatively. Six of
them were refused for surgery due to extension of splenic vein thrombosis into
the portal vein. Two patients without extrinsic compression of the vein were
treated with anticoagulants. 16 patients were treated by surgery with low
morbidity and without mortality. The standard treatment in fourteen cases was
splenopancreatectomy. The average follow-up of seven years shows that these
patients have preserved their body mass index (BMI). The results suggest that
early surgical intervention is beneficial in preventing progression of SVT to the
portomesenteric vein.
PMID- 9653824
TI - [Pancreatic pseudocysts: choice of treatment?].
AB - Pseudocysts of the pancreas may require drainage or resection during their
evolution. External drainage can be considered as a treatment of first resort
with low related morbidity. It also offers a means of treating patients with
major contraindications for surgery. In our experience, however, only 55% of
external drainages prove successful. Therefore, surgical treatment, even at the
cost of low-rate morbidity, remains the only final treatment for complications
linked to pseudocysts of the pancreas. In the long term, however, these results
depend on the etiology of the pseudocysts.
PMID- 9653825
TI - [Prevalence of upper abdominal complaints and their effect on the quality of life
and utilization of medical resources. Swiss Primary Care Group].
AB - The authors present the results obtained in Switzerland, as part of an
international survey (DIGEST), on 3 months' prevalence of upper digestive
symptoms (UDS) and their influence on quality of life and consumption of medical
services. 514 randomized adults from the general population in 8 different cities
were interviewed. In these interviews data were recorded concerning demographic
and socio economic aspects, quality of life, severity and frequency of UDS,
consultations and medication. The sub-population with relevant UDS (i.e. UDS at
least once a week and/or of moderate to severe degree) was compared with the rest
of the population interviewed. 19% of the interviewees reported relevant UDS; of
these, two thirds were women. No differences were found between people with and
without UDS as far as education, professional activities, consumption of alcohol
or smoking are concerned. The most frequent symptoms reported were fullness,
bloating and nausea. However, daily activities were most impaired by nausea,
epigastric pain and heartburn. Interviewees with UDS more frequently reported
"life events" in the preceding year (48% vs 33%). Interviewees with UDS also more
frequently reported back pain (7% vs 2%) and migraine (10% vs 6%). Furthermore,
more interviewees with UDS reported sick leave (11% vs 3%); they also had a
poorer life quality score (74 vs 89, PGWBI), reported more medical visits (50% vs
19%) and consumed more medication, both prescribed (65% vs 25%) and non
prescribed (OTC: 70% vs 31%).
PMID- 9653826
TI - [Validation of the "Digest Questionnaire" for consistency and reproducibility
with reference to upper abdominal symptoms].
AB - "Digest" is a international effort to record the prevalence of digestive symptoms
in the general population. The international questionnaire was tested in German
translation for reliability and reproducibility. The questionnaire consists of 14
symptoms, which were investigated by standardized questions. Each symptom was
described in 3 dimensions: frequency, severity and impact on daily activities.
127 successive patients referred for upper gastrointestinal endoscopy were
interviewed twice by a young assistant and by an experienced gastroenterologist
before the diagnostic work-up. A further 72 volunteers served as a control group.
In these volunteers no upper gastrointestinal endoscopy was performed.
Reliability and reproducibility were calculated by the Spearman rank test. The
most frequent diagnoses were: organic diseases (oesophagitis [28], gastric
ulcer/erosive gastritis [32] and duodenal ulcer [18]); functional diseases
(dyspepsia [32] and irritable bowel syndrome [14]). Reproducibility was
satisfactory by accepted standards (p > 0.7). Reliability was very good, with r
values for each symptom between p 0.96-0.99. The impact on daily activities was
highest in the case of heart-burn or localized upper gastrointestinal pain, and
lowest in the case of belching and fullness. The questionnaire can be easily
administered by the non-specialist and the results discriminate well between
functional/organic diseases and healthy people, thanks to excellent
reproducibility and reliability.
PMID- 9653827
TI - [Intracardiac "umbrella" with anemia].
PMID- 9653828
TI - Effects of Epoetin alfa on hemostasis in chronic renal failure.
AB - Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage
renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been
demonstrated to affect hemostasis. Such effects may be important because patients
with chronic renal failure have a bleeding diathesis that is multifactorial in
origin. Therefore, a computer literature search on the relationship between
Epoetin alfa therapy for anemia in patients with end-stage renal disease and
platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed.
All articles and abstracts reporting original data in the English language on
Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests
that the effects of Epoetin alfa on the coagulation cascade are of minimal
clinical importance. However, Epoetin alfa transiently increases the number of
circulating platelets and improves platelet function, and these effects are
associated with a return of the bleeding time towards normal.
PMID- 9653829
TI - Persistent high prevalence of thyroid antibodies after immunosuppressive therapy
in subjects with glomerulonephritis. A prospective three-year follow-up study.
AB - The prevalence of thyroid antibodies, indicating an autoimmune thyroiditis, has
been shown to be significantly increased in patients with autoimmune diseases. A
3-year prospective follow-up study of 42 patients with biopsy-confirmed
glomerulonephritis is presented. Although the majority of patients had been
treated with immunosuppressants, the prevalence of thyroid peroxidase antibodies
was unchanged in both females and males, 47 and 15% respectively, at follow-up.
Likewise, the prevalence of thyroglobulin antibodies was unaffected as was that
of antinuclear antibodies (ANA) when analysing males and females together.
However, for males there was a trend to higher prevalence for ANA at follow-up.
On the other hand, the prevalence of antineutrophil cytoplasmic antibodies
declined. Furthermore, thyroid antibodies were not restricted to membranous
nephropathy, and notably found in 4 out of the 8 patients with vasculitis.
PMID- 9653830
TI - Determinants of ventricular arrhythmias in hemodialysis patients. Evaluation of
the effect of arrhythmogenic substrate and autonomic imbalance.
AB - BACKGROUND/AIMS: In chronic hemodialysis patients, we evaluated determinants of
repetitive ventricular tachyarrhythmias which included late potentials and heart
rate variability. METHODS: We compared the presence of late potentials and heart
rate variability obtained by ambulatory electrocardiogram (ECG), findings of
echocardiography, and laboratory data between patients with and those without
ventricular arrhythmias of Lown class 4A or 4B. Ambulatory ECG was recorded for
24 h from the beginning of hemodialysis. Heart rate variability was evaluated by
the standard deviation of the normal RR interval (SDNN). RESULTS: Thirty patients
(17%) had ventricular arrhythmias of Lown class 4A or 4B. They were older than
patients without such arrhythmias (p=0.0021). Left-ventricular wall motion score
(2.0+/-3.9 and 0.3+/-1.2, respectively, p < 0.0001) and left-ventricular mass
index (167 +/-59 and 140+/-44 g/m2, respectively, p=0.0053) were larger in
patients with ventricular arrhythmias of Lown class 4A or 4B than in those
without. Stepwise logistic regression analysis was performed to select variables
related to ventricular arrhythmias of Lown class 4A or 4B from the following 8
candidate variables; age, sex, presence of ischemic heart disease, diabetic
nephropathy as the primary renal disease, presence of late potentials, SDNN, left
ventricular wall motion score and left-ventricular mass index. Higher left
ventricular wall motion score (p < 0.0001), older age (p=0.0022) and male sex
(p=0.0235) were the variables associated with ventricular arrhythmias of Lown
class 4A or 4B. CONCLUSION: In patients receiving hemodialysis, predominantly
with chronic glomerulonephritis, ventricular arrhythmias of Lown class 4A or 4B
were not associated with arrhythmogenic substrate revealed by late potentials or
autonomic dysfunction assessed by heart rate variability. Left-ventricular wall
motion abnormalities, age and sex were significant factors.
PMID- 9653831
TI - Can total urinary protein measurements predict microalbuminuria?
AB - We re-addressed the question of whether routine total urinary protein
determinations can be used to predict the presence of microalbuminuria by
studying 61 patients who attended a diabetic clinic and tested negative or had
one positive protein by dipstick. Total urinary protein was measured by the
Biorad dye-binding method in undialyzed urine (UND), in dialyzed urine (DIAL),
and in dialyzed urine in which albumin and globulins were separated, measured
separately with albumin and globulin standards and the results added together to
obtain total urinary protein (A + G). The results were compared with albumin
measurements obtained by radioimmunoassay (RIA). Compared to DIAL, urinary
protein measurements were 43% higher with A + G and 22% higher with UND.
Microalbuminuria correlated moderately with UND (r =0.81) and better with the
other methods (r=0.87 for DIAL, r=0.91 for A + G). None of the methods predicted
microalbuminuria reliably. Taking a protein-to-creatinine ratio of 0.15 and an
albumin-to-creatinine ratio of 0.03 as upper limits of normal, we found that UND
had a 72% positive predictive value (28% false positives) and 85 % negative
predictive value (15% false negatives). DIAL had 90% positive predictive value
(10% false positives) and 78% negative predictive value (22% false negatives). A
+ G had 65% positive predictive value (35% false positives) but 91% negative
predictive value (9% false negatives). A + G, which uses the correct standards,
would be the most suitable method for screening, having the least number of false
negatives, but has more false positives because it is more sensitive. In
practice, most routine chemical laboratories find it expedient to use only UND,
but physicians interpreting the results of this method should be aware of its
limitations.
PMID- 9653832
TI - Mesangial proliferative nephritis in man is associated with increased expression
of the cell survival factor, Bcl-2.
AB - Although most studies suggest that the hypercellularity in mesangial
proliferative nephritis is due to increased cell proliferation, we hypothesized
that it may also be due to increased expression of survival factors that may
block their removal (apoptosis). We therefore studied the expression of apoptosis
preventing/delaying the bcl-2 gene product in the glomerulus with various human
glomerulonephritides. Immunohistochemistry for Bcl-2, proliferating cell
associated protein (Ki-67) and alpha-smooth muscle actin (alpha-SMA) was
performed on 55 biopsied kidney tissues: 6 cases of orthostatic proteinuria as a
control (OP); 6 cases of diffuse proliferative lupus nephritis (WHO type IV, LN
MPGN); 24 cases of IgA nephropathy (IgA); 9 cases of minimal change nephrosis and
10 cases of idiopathic membranous nephropathy. The number of Ki-67-positive cells
and the expression of alpha-SMA in the glomerulus were significantly higher in LN
MPGN and IgA. There was a significant positive correlation between glomerular Bcl
2 expression and glomerular cell proliferation evaluated by the number of Ki-67
positive cells (r=0.605, p < 0.01) or glomerular alpha-SMA expression (r=0.674, p
< 0.01). Glomerular expression of Bcl-2 in IgA or LN-MPGN was significantly
higher than that in OP (p < 0.01 and p < 0.05 vs. OP, respectively). The Bcl-2
positive cells were present in mesangial locations and demonstrated a perinuclear
pattern. These results suggest that maintenance of glomerular hypercellularity in
human glomerular diseases is partly due to the prevention of mesangial cell death
via Bcl-2 expression.
PMID- 9653833
TI - Predicting hemodialysis access failure with color flow Doppler ultrasound.
AB - Color flow doppler ultrasound examination of the hemodialysis access was
conducted in 2,792 hemodialysis patients to evaluate its value in predicting
hemodialysis access failure. After baseline assessment of vascular access
function with clinical and laboratory tests including color flow doppler
evaluation these patients were followed for a minimal of 6 months or until graft
failure occurred (defined as surgery or angioplasty intervention, or graft loss).
The patient demographics and vascular accesses were typical of a standard
hemodialysis patient population. On the day of the color flow doppler examination
systolic and diastolic blood pressure, hematocrit, urea reduction ratio, dialysis
blood flow, venous line pressure at a dialysis blood flow of 250 ml/min, and
access recirculation rate were measured. At the conclusion of the study 23.5% of
the patients had access failure. Case mix predictors for access failure were
determined using the Cox Model. Case mix predictors of access failure were race,
non-white was higher than white (p < 0.005), younger accesses had a higher risk
than older accesses (p < 0.025), accesses with prior thrombosis had a higher risk
of failure (p=0.042), polytetrafluoroethylene (PTFE) grafts had a higher risk
than native vein fistulae (p < 0.05), loop PTFE grafts had a higher risk than
straight PTFE grafts (p < 0.025), and upper arm accesses had a higher risk than
forearm accesses (p=0.033). Most significant, however, was decreased access blood
flow as measured by color flow doppler (p < 0.0001). The relative risk of graft
failure increased 40% when the blood flow in the graft decreased to less than 500
ml/min and the relative risk doubled when the blood flow was less than 300
ml/min. This study has shown that color flow doppler evaluation, quantifying
blood flow in a prosthetic graft, can identify those grafts at risk for failure.
In contrast, color doppler volume flow in native AV fistulae could not predict
fistula survival. This technique is noninvasive, painless, portable, and
reproducible. We believe that preemptory repair of an anatomical abnormality in
vascular access grafts with decreased blood flow may decrease patient
inconvenience, associated morbidity, and associated costs.
PMID- 9653834
TI - Metalloproteinase-9 mRNA expression in monocytes from patients with chronic renal
failure.
AB - Long-term dialysis patients suffer from various complications including
atherosclerosis. It has been suggested that metalloproteinases (MMPs) contribute
to vascular remodeling during the development and progression of human
atherosclerosis. Activated human monocytes have been demonstrated to secrete
MMPs. In the present study, we measured levels of MMP mRNA in peripheral blood
monocytes obtained from patients on continuous ambulatory peritoneal dialysis
(CAPD) or hemodialysis (HD) and chronic-renal-failure patients not undergoing
dialysis. Twenty patients with chronic renal failure were not undergoing
dialysis, 20 patients were on CAPD, 40 patients were on chronic HD and 20 healthy
volunteers served as controls. We used cDNA probes encoding for MMP-1, MMP-2, MMP
3 and MMP-9 and glyceraldehyde phosphate dehydrogenase. Higher levels of MMP-9
mRNA in the peripheral blood monocytes were observed in HD patients than in CAPD
patients, undialyzed chronic renal failure patients or healthy controls. MMP-9
mRNA levels at the end of HD were not significantly higher than those at the
start of HD. MMP-9 mRNA levels from HD patients did not differ among the types of
membranes. We could detect minimal MMP-1, MMP-2 and MMP-3 mRNA expression in
monocytes from all groups. Serum gelatinase activity was detectable in all
samples; however, no significant differences existed among the groups. In
summary, MMP-9 mRNA expression is enhanced in monocytes from HD and CAPD
patients, and the enhancement may be, in part, associated with cardiovascular
complications, including atherosclerosis, in dialysis patients. This increase in
monocyte MMP-9 mRNA levels is lower in CAPD patients that it is in HD patients.
PMID- 9653835
TI - A simple assessment of peritoneal transport in stable continuous ambulatory
peritoneal dialysis patients.
AB - We studied the peritoneal transport properties in 175 stable continuous
ambulatory peritoneal dialysis (CAPD) patients seeking a simple and handy
assessment of peritoneal permeability to small solutes. Measurement of creatinine
in biological fluid was known to suffer from interference by high glucose
concentration in the sample. Furthermore, the interference is also affected by
the creatinine concentration of the specimen. Peritoneal transport properties
were studied by determining the dialysate to plasma ratio of creatinine
concentration (D/P) at the fourth hour of the peritoneal equilibration test, and
the mass transfer area coefficient of creatinine (MTACCr) or glucose (MTACGlu).
The ratio of glucose concentration in peritoneal dialysate effluent (PDE) at 4
and 0 h (G4/G0) was examined and compared with various peritoneal parameters.
There were significant logarithmic correlations between D/P or G4/G0 with MTACCr
(r=0.96 and 0.79, respectively, p < 0.0001). The correlation between G4/G0 and
D/P was linear (r=-0.82, p < 0.0001). A fairly good agreement was present between
G4/G0 and D/P by Bland and Altman's method. The bias was -0.93% with 95%
confidence interval -23.29% to 21.43% of the measured value. Systematic error was
found when D/P or G4/G0 were compared with MTACCr. D/P under estimated MTACCr in
the high range. The reverse happened for G4/G0. Net ultrafiltration (NUF) also
correlated with MTACCr, D/P and G4/G0 (r=-0.32, p < 0.001; -0.26, p < 0.01; and
0.16, p < 0.05, respectively. In conclusion, the use of G4/G0 as a measure of
peritoneal transport in CAPD is an acceptable alternative to D/P. It is highly
reproducible and avoids correction of interference when creatinine transport
parameters are measured. Because of the logarithmic relations of G4/G0 (or D/P)
with MTACCr, the former should not be directly converted to MTACCr. Such a simple
measure of peritoneal permeability is, however, most convenient for serial
monitoring and can be useful to detect early loss of ultrafiltration or solute
clearance.
PMID- 9653836
TI - Duodenal obstruction in polycystic kidney disease. Case report and review of the
literature.
AB - Polycystic kidney disease in a common inherited disorder accounting for 8-10% of
cases of end-stage renal disease. The enlarged kidneys often produce pain and
hematuria but rarely obstruction of surrounding organs. We report a case of
autosomal dominant polycystic kidney disease producing symptomatic duodenal
obstruction and malnutrition. Duodenal obstruction should be considered in the
differential diagnosis of a patient with polycystic kidney disease and
intermittent or persistent nausea and vomiting.
PMID- 9653837
TI - End-stage renal failure due to crescentic glomerulonephritis in a patient with
Behcet's syndrome. Review of the literature.
AB - We report a rare case of a patient with Behcet's syndrome who developed end-stage
renal failure due to crescentic glomerulonephritis (GN). A 20-year-old male
patient had suffered from uveitis, aphthous mouth ulcers and genital ulceration
for the past 7 years. His renal function rapidly deteriorated and renal biopsy
specimens obtained when his serum creatinine level was 3 mg/dl showed diffuse
proliferative GN with fibrous crescent formation in 75% of glomeruli excluding
totally sclerotic glomeruli. Immune complexes were identified by demonstration of
complement and immunoglobulins in the glomeruli. He developed end-stage renal
failure during a 1-year course and received maintenance hemodialysis. We reviewed
the literature on severe forms of GN in patients with Behcet's syndrome.
PMID- 9653838
TI - Treatment of pulmonary embolism by subcutaneous low-molecular-weight heparin in a
hemodialysis patient.
AB - Low-molecular-weight heparin (LMWH) has been used in the prophylaxis and
treatment of deep vein thrombosis. Data regarding the efficacy of this drug
without subsequent use of oral anticoagulant in the treatment of pulmonary
embolism is limited. Pulmonary embolism may complicate the use of central venous
catheter in hemodialysis. We report a case of acute submassive pulmonary embolism
complicating a central venous hemodialysis catheter in a dialysis patient. After
the catheter was removed, the patient was treated successfully with subcutaneous
injection of LMWH for three months. We conclude that LMWH is safe and effective
for treatment of pulmonary embolism in patient on hemodialysis.
PMID- 9653839
TI - Acute anuric renal failure in nonfulminant hepatitis A infection.
AB - Acute renal failure has recently been recognized as a rare complication of
nonfulminant hepatitis A infection. The availability of a specific test for IgM
antibody to hepatitis A should permit prompt diagnosis of the disease and a
better evaluation of its association with acute renal failure. The exact
mechanism for acute renal failure in hepatitis A is uncertain but
glomerulonephritis, acute tubular necrosis and hepatorenal syndrome have been
postulated. We report a patient with hepatitis A infection and acute renal
failure most likely due to acute tubular necrosis.
PMID- 9653840
TI - Systemic involvement and uremia in a patient with tuberous sclerosis.
PMID- 9653841
TI - Immunotactoid glomerulopathy associated with idiopathic hypereosinophilic
syndrome.
AB - A case of immunotactoid glomerulopathy in an 18-year-old man with an idiopathic
hypereosinophilic syndrome is presented. The patient showed cervical
lymphadenopathy, asymptomatic proteinuria of nephrotic range, and hematuria
without any defined immunologic disease. Marked and prolonged hypereosinophilia
was found in peripheral blood (eosinophil count; 6,248/mm3) and bone marrow
(eosinophil series; 32%). Diffuse and/or nodular eosinophilic infiltration was
identified in multiple organs such as kidney, stomach, liver, lymph node, and
skin. Renal biopsy revealed endocapillary proliferative features of typical
immunotactoid glomerulopathy with IgG and C3 deposition and microtubular
structures of variable size, 20-80 nm in diameter, mainly in the subendothelium.
This study suggests that immunotactoid glomerulopathy may be a secondary
immunologic manifestation of the tissue damage by eosinophils in the idiopathic
hypereosinophilic syndrome.
PMID- 9653842
TI - Oxidative modification of low-density lipoprotein enhances mesangial cell protein
synthesis and gene expression of extracellular matrix proteins.
AB - The proliferation of intrinsic glomerular cells and the accumulation of
extracellular matrix proteins are principal histopathological features seen in
glomerular injury. Because of the marked similarity between the cellular and
molecular events that occur in both atherosclerosis and glomerulosclerosis and
the commonly accepted hypothesis that lipoproteins are implicated in the
pathogenesis of glomerulosclerosis, we examined the effect of three atherogenic
lipoproteins, low-density lipoprotein (LDL), oxidized (ox)-LDL, and minimally
modified (mm)-LDL on the synthesis and secretion of extracellular matrix (ECM)
proteins by mesangial cells. The incubation of SV-40 transformed murine mesangial
cells with LDL (25-100 microg/ml) increased the synthesis and secretion of both
fibronectin and laminin in a dose-dependent manner. Similarly, oxidized forms of
LDL (25-100 micro/ml) increased fibronectin and laminin synthesis and secretion
dose dependently. However, both oxidatively modified forms of LDL had a greater
effect on increasing ECM protein synthesis than their native counterpart.
Northern blot analysis showed a dose-dependent increase in mRNA transcripts for
fibronectin and laminin in response to the incubation of mesangial cells with
LDL, ox-LDL, and mm-LDL. Similar to the ECM protein expression data, the
oxidatively modified forms of LDL had more pronounced effects on the gene
expression of both fibronectin and laminin. These data show that both LDL and,
perhaps more importantly, its oxidatively modified forms stimulate mesangial
cells to upregulate both the gene expression and synthesis and secretion of ECM
proteins, supporting a role for atherogenic lipoproteins in the pathobiology of
glomerular injury.
PMID- 9653843
TI - Arterial CO2 tension in metabolic acidosis.
PMID- 9653845
TI - Incidence of preterm delivery in Hong Kong Chinese.
AB - A retrospective analysis of the obstetric database between January, 1995 and
December, 1996 was conducted to establish the rate of preterm birth and the
incidence of babies with low birth-weight amongst Hong Kong Chinese in an
obstetric teaching unit in Hong Kong, and to investigate possible risk factors
for spontaneous preterm deliveries. In the series of 13,641 Chinese women who
delivered during the study period, the incidence of preterm births before 37
weeks' gestation was 7.4% while the incidence of low birth-weight infants
(<2,500g) was 6.4%. When only singleton pregnancies were included, the incidences
of preterm births and low birth-weight were 6.5% and 5.1% respectively. This
study has demonstrated results contrary to the belief that premature delivery is
uncommon in a Chinese population. In addition, we have found that, similar to
Caucasian populations, hypertensive disorders of pregnancy, gestational diabetes,
antepartum haemorrhage and congenital malformation are significant risk factors
for spontaneous preterm labour in singleton pregnancy in our Chinese population.
PMID- 9653844
TI - Differences in obstetrical and gynaecological diseases in different populations:
prevalences of prematurity, congenital malformations, prolapse, genital tract
carcinomas and infections.
PMID- 9653846
TI - Hormone replacement therapy in the developing countries.
AB - The sales data of oestrogen replacement products for 8 developing countries from
1993 to 1995 were analyzed. The data from Malaysia, Pakistan, Taiwan, Thailand,
Indonesia, Philippines and South Korea showed the increasing use of oestrogen
replacement products. The total usage however varied widely, from only US$11,153
(Philippines in 1993) to as much as US$6,306,717 (Taiwan in 1995). In Singapore,
where oestrogen replacement is an accepted and established form of therapy for
the postmenopausal woman, there has been an increase in the usage of the
nonoestrogen replacement products. There are multiple reasons for the increasing
sales of hormone replacement products in the developing countries and these are
explored in this article. In some of the developing countries, for example China
and India, hormone replacement therapy has just been introduced. However, in
those developing countries in which hormone replacement therapy is already
available, sales figures show increasing usage. The future augurs well for
hormone replacement therapy.
PMID- 9653847
TI - A systematic review of single-dose intramuscular methotrexate for the treatment
of ectopic pregnancy.
AB - The use of single-dose intramuscular methotrexate for the primary treatment of
ectopic pregnancy is increasing in frequency in many countries. We performed a
systematic review of all available studies and case reports of intramuscular
methotrexate to examine the therapeutic efficacy, side-effects and complication
rates of this new treatment approach. The pooled data show a successful
resolution rate of 71% (95% confidence interval 58% to 81%) after a single dose
of intramuscular methotrexate and 84% (95% confidence interval 77% to 90%) after
1 or 2 doses. Side-effects were experienced by 24% (95% confidence interval 9% to
47%) of patients and 10% (95% confidence interval 7% to 14%) had a ruptured
ectopic pregnancy. The pooled data show that single-dose intramuscular
methotrexate is associated with a high failure rate. Follow-up is prolonged and
there is a significant incidence of minor side-effects. Serious complications and
side-effects have occurred. The use of intramuscular methotrexate should be
confined to clinical trials until more evidence is obtained to support its more
widespread use.
PMID- 9653848
TI - Heterotopic pregnancy complicating in vitro fertilization.
AB - A review was undertaken of the cases of heterotopic pregnancy resulting from in
vitro fertilization/embryo transfer (IVF/ET) and frozen embryo replacement (FER)
in a 6-year cohort of women at National Women's Hospital in Auckland. The
incidence of heterotopic pregnancy was 2.9% (5 cases) in 173 clinical pregnancies
resulting from 901 embryo replacements. Of the 5 women with heterotopic
pregnancy, 1 had unilateral tubal patency and 4 had bilateral tubal blockage; 3
had 'high responder' peak serum oestradiol levels (greater than 9,000 pmol/L)
prior to oocyte pick-up (OPU); 3 had a serum human chorionic gonadotrophin beta
subunit (beta-HCG) level greater than 600 IU/L on Day 14 following embryo
transfer (ET) in the absence of a multiple intrauterine gestation on subsequent
ultrasound scan. In the 4 women in whom unequivocal diagnosis of heterotopic
pregnancy was not made on the initial ultrasound scan, there was delay in
appropriate management, in 1 for more than 5 months. In conclusion, early IVF
pregnancies require a transvaginal ultrasound scan performed by a sonographer
experienced in the diagnosis of ectopic pregnancy and management of early
pregnancy complications by clinicians in close consultation with the IVF centre
itself. No single risk factor, laboratory test or combination of these is
sensitive or specific enough to predict the occurrence of heterotopic pregnancy.
The first-line surgical treatment of heterotopic pregnancy should be laparoscopic
salpingectomy with excision of all except the intramural portion of the affected
Fallopian tube.
PMID- 9653849
TI - Haemoperitoneum due to cornual endometriosis during pregnancy resulting in
intrauterine death.
PMID- 9653850
TI - Genital tract fistula repair on 116 women.
AB - A personal series of 130 genital tract fistula repairs in 116 women is presented.
All fistulas were repaired vaginally. The majority of the fistulas were due to
obstetric injuries, especially prolonged obstructed labour. Obstetric fistula
continue to be a cause of personal and social morbidity to sufferers.
PMID- 9653851
TI - Abnormal cervical cytology in pregnancy: experience of 811 cases.
AB - This paper reviews our hospital's experience spanning 15 years and involving 811
women referred with abnormal cervical cytology in pregnancy. It supports the
safety and accuracy of managing dysplasia in pregnancy with colposcopy, directed
punch biopsy and deferral of treatment until the postpartum period. The
histologically-proven progression in pregnancy to a higher grade of dysplasia
postpartum was 7%. None of the women are known to have developed microinvasive or
invasive cancer between antenatal assessment and postpartum review. Of these 811
women, 16% were lost to follow-up, 1 of whom subsequently represented 4 years
later with invasive cervical cancer.
PMID- 9653852
TI - Perioperative documentation: are we doing enough?
AB - We performed a retrospective analysis to assess the content and accuracy of
operative and anaesthetic records for Caesarean section in a large unit. The
obstetric record was considered adequate if it included patient identification,
participating doctors, operative date, title, details and findings and a
signature. The anaesthetic record was evaluated by The Australian and New Zealand
College of Anaesthetists guidelines. We analysed 104 operative and 101
anaesthetic records. There was inadequate identification in 17 (16.3%) of the
operative records. Documentation of a previous scar or the presence or absence of
intraabdominal adhesions was incomplete in 22 of the 35 patients (63%) with a
previous laparotomy. Sixty per cent of records had incomplete skin closure
information. Common anaesthetic record deficiencies were patient position,
patient airway, investigation results and postoperative plan. Our findings
identified deficiencies that could lead to inadequate medical care and indicate
the need for improved standards of perioperative records.
PMID- 9653853
TI - Oral medication for post-Caesarean analgesia.
AB - A regimen of morphine, paracetamol and aspirin administered orally was evaluated
in 20 patients following Caesarean section; 18 of 20 reported no or mild
impairment in their ability to care for their babies. There was a high level of
satisfaction with 18 of 20 being very satisfied with their postoperative
analgesia. There was a low incidence of side-effects with this regimen. It was
acceptable to both patients and staff.
PMID- 9653854
TI - Do multiple measurements employing different ultrasonic techniques improve the
accuracy of amniotic fluid volume assessment?
AB - This investigation was undertaken to determine if the accuracy of the ultrasound
assessment of abnormal amniotic fluid volume (oligohydramnios or polyhydramnios)
is improved by employing multiple sonographic amniotic fluid measurements. Four
ultrasound techniques consisting of the subjective assessment (ultrasonic
visualization without measurement), largest vertical pocket, amniotic fluid index
and 2-diameter pocket technique were performed followed by amniocentesis and dye
dilution confirmation of amniotic fluid volume in 66 singleton pregnancies. The
ultrasound accuracy to detect abnormal amniotic fluid volume ranged from 61% with
the largest vertical pocket to 70% with the 2-diameter pocket procedure used
separately. Receiver operator characteristic curves demonstrated that combining
the 4 ultrasonic measurements did not improve the accuracy of identifying
amniotic fluid volumes.
PMID- 9653855
TI - The relationship between weight gain in pregnancy, birth-weight and postpartum
weight retention.
AB - A total of 292 middle class, nonsmoking Chinese patients with known prepregnant
weight who subsequently had uncomplicated singleton pregnancies delivering after
36 weeks' gestation were recruited to assess their serial antenatal weight gain,
weight at 6 weeks and 3 months postpartum. The average prepregnant body mass
index in the whole group was 20.4 kg/m2 (SD 2.19), and the total pregnancy weight
gain was 14 kg (SD 3.75). Those with weight gain over 17.83 kg (one SD above the
mean) (n=58) had higher weight gain in all 3 trimesters taken separately, as well
as higher weight retention at 6 weeks and 3 months postpartum (p <0.001). Similar
differences were noted for those with total weight gain over 2 standard
deviations above the mean. The average weight retained at 3 months postpartum was
3.64 kg (SD 2.75). Those with weight retention over 9.14 kg (2 SD above the mean)
(n=8) had a significantly higher second and third trimester weight gain (p <0.01)
compared to the rest. These data suggest that excessive weight gain during
pregnancy for women with prepregnant BMI in the normal range occurred most
significantly after the mid-trimester, and was associated with higher postpartum
weight retention without significant increase in birth-weight.
PMID- 9653856
TI - Cystic fibrosis and pregnancy.
AB - The case records of 11 patients with cystic fibrosis (CF) who had 13 completed
pregnancies between 1975 and 1995 were retrospectively reviewed to assess: (1)
the changes in spirometry and body mass index (BMI) during pregnancy; and (2)
maternal and neonatal complications and outcomes. Prepregnancy the mean age of
the group was 24 (range 17-27) years. Two patients were exsmokers, 7 had
pancreatic insufficiency and 7 had chest X-ray evidence of bronchiectasis. None
of the patients had diabetes mellitus but 3 developed gestational diabetes. The
mean +/- SEM (% predicted) forced expiratory volume in 1 second (FEV1) and forced
vital capacity (FVC) prepregnancy were 2.3 +/- 1.0 (83%) litres and 3.0 +/- 0.9
(85%) litres respectively. Five patients had normal spirometry (FEV1 and FVC >80%
predicted) prior to 6 pregnancies. The mean body mass index (kg/height(m)2) for
the group was 20.5 +/- 2.0. There was a significant decline in spirometry during
pregnancy (FEV1 15.5 +/- 6.6% p<0.01; FVC 14.0 +/- 8.3% p<0.5). However, FVC but
not FEV1 recovered to prepregnancy values by 12 months postpartum. There was a
significant increase in both weight (7.1 kg) and BMI (2.6 kg/height(m)2) at the
time of delivery compared with prepregnancy (p=0.0004). However, postpregnancy
both weight and BMI had returned to their prepregnancy values (p<0.2). Mothers
with an FEV1>80% had less decline in FEV1 related to pregnancy, better outcomes,
fewer operative and instrumental deliveries, fewer preterm infants and fewer
neonatal complications. Suggestions for the planning and management of pregnancy
in women with CF are discussed.
PMID- 9653857
TI - Study of cervicovaginal fetal fibronectin status to guide treatment of threatened
preterm labour.
AB - A sequential controlled pilot study of 48 women (16 study, 32 controls) was
performed to explore the place of bedside fetal fibronectin testing in the
management of apparent preterm labour; 80% of the study group were successfully
managed without tocolytic therapy, on the basis of fetal fibronectin test
results, without detriment to the babies. Rapid bedside fetal fibronectin testing
holds promise that protocols for management of women in apparent preterm labour,
with intact membranes and without significant cervical dilatation, may be altered
so that most of the unnecessary use of tocolytic drugs is avoided.
PMID- 9653858
TI - Diet and nutrition: a knowledge, attitude and practice study of pregnant women in
Karachi.
PMID- 9653859
TI - Which Korotkoff sound should be used for the diastolic blood pressure in
pregnancy?
AB - There is a gathering momentum favouring the adoption of the 5th Korotkoff sound
to identify diastolic blood pressure in pregnancy. Our objective was to measure
interobserver reliability for indirect blood pressure measurement in pregnancy
for systolic and diastolic measurements and to calculate the difference in
diastolic pressure measured by the 4th and 5th Korotkoff sounds. To minimize bias
we used trained but previously inexperienced observers with proven, normal
auditory acuity. The observers were paired in 4 teams and performed a series of
334 blinded, simultaneous observations of systolic and diastolic blood pressure
measurements taken from pregnant women between 12-41 weeks' gestation.
Reliability was measured by intraclass correlation coefficient for paired
measures and kappa for the detection or nondetection of 4th (K4) and 5th (K5)
Korotkoff sounds. K4 was undetected in 36% of observations and K5 was undetected
in 2% of observations. Reliability for detection or nondetection of Korotkoff
sounds was fair for K4 (kappa 0.36) and moderate for K5 (kappa 0.58). Reliability
was good between observers for systolic, K4 and K5 diastolic measurements
(intraclass correlation > or = 0.80). The mean difference between the diastolic
pressure measured by K4 and K5 was 15 mmHg for all measurements and 8 mmHg for
the top quartile of measurements (p <0.001). We found K5 to be more often and
more reliably detected than K4. If units adopt K5 in preference to K4,
consideration will need to be given to lowering treatment thresholds for women
with borderline or mild hypertension.
PMID- 9653860
TI - Blood pressure measurement in pregnancy--a survey of methods used in teaching
hospitals in South Australia.
AB - A voluntary, anonymous 10-point multiple choice questionnaire was used to assess
variability in methods used to measure blood pressure in pregnancy in 5 South
Australian teaching hospitals. Medical and midwifery staff working in maternity
units attached to teaching hospitals in South Australia were asked to complete a
survey of their current practice related to the measurement of blood pressure in
pregnant women; 213 replies were received from 440 surveyed (48% response rate).
There was a lack of standardization of practice for: positioning of the patient,
use of the 4th or 5th Korotkoff sound for diastolic blood pressure, cuff
selection, rounding of the measurement, selection of the left or right arm, and
period of premeasurement resting. Systematic errors averaging 10-15 mmHg can be
expected in measurement of blood pressure in pregnancy due to failure of
standardization of method. There is a need for standardization of method which is
not being met by present methods of staff training in teaching hospitals.
PMID- 9653862
TI - Fetal biomodelling.
AB - A study has been performed to determine if a stereolithographic (SL) biomodel of
a fetal face could be created from 3 dimensional (3D) ultrasound (US). 3D
ultrasound images were acquired by Diasonics Gateway 2D Array ultrasound systems
(Diasonics Ultrasound, San Jose, CA, USA) using an electromagnetic localizer
(Tomtec Free Hand Scanning Device, Tomtec Imaging Systems, Middle Cove,
Australia). 3D volumetric reconstruction of the fetal face was performed and the
data was prepared to guide the construction of an exact solid biomodel by
stereolithography (SLA 250 3D Systems, Valencia, CA, USA). A faithful solid
representation of the fetal face was produced within 12 hours of the US scan. The
fetal biomodel seemed to improve the display of the 3D data. The user-friendly
nature of biomodelling may have clinical utility for fetal morphological
assessment and as an aid when counselling parents.
PMID- 9653861
TI - Changes of resistance to activated protein C in the course of pregnancy and
prevalence of factor V mutation.
AB - The purpose of this study was to examine the changes in activated protein C (APC)
anticoagulant activity during pregnancy and determine whether changes in APC
could contribute to thrombosis in the placental bed in preeclampsia. We measured
APC anticoagulant activity in 150 women with a normal pregnancy and 50 women with
preeclampsia. There was a significant reduction in the mean APC sensitivity ratio
(APC-SR) during pregnancy (p<0.001). APC resistance in preeclampsia was
significantly higher than in normal pregnancy (p<0.01). Amongst women with APC
resistance the presence of the factor V Leiden mutation was significantly higher
in the preeclampsia group than in the normal pregnancy group (p<0.01). It seems
that both factor V Leiden mutation and APC resistance may be associated with the
development of preeclampsia. These results suggest that APC resistance may be an
important mechanism underlying placental bed pathology in pregnancy and may be
associated with an increased tendency to develop preeclampsia in some women.
Assay of APC resistance and factor V Leiden mutation should be performed in women
with preeclampsia.
PMID- 9653863
TI - The effects of human amniotic membrane and fibrin sealant in the prevention of
postoperative adhesion formation in the rabbit ovary model.
AB - The study group consisted of 29 female, white New Zealand rabbits. The rabbits
were randomized into 3 groups and a midline laparotomy was performed in order to
make a 4-5 mm long lesion using a scalpel in both ovaries. In Group 1, both of
the ovaries were left uncovered. In Group 2, the right ovaries were covered by
human amniotic membrane graft. In Group 3, 0.1-0.2 mL of Tisseel solution was
applied to the lesion in the right ovaries. No medication was applied to the left
ovaries in any of the groups and thus this ovary acted as an individual control.
After 2 weeks the adhesion scores were graded by relaparotomy in a blind manner.
Fibrin sealant showed a significant reduction in postoperative adhesion formation
compared with the amniotic membrane graft and control groups (p<0.001).
Therefore, it can be concluded that fibrin sealant can be used as an adjuvant
during reproductive surgery.
PMID- 9653864
TI - The effects of danazol after endometrial resection--results of a randomized,
placebo-controlled, double-blind study.
AB - We report the results of a controlled, randomized, prospective, 'double blind'
evaluation of the effect of danazol treatment in 120 patients after hysteroscopic
endometrial resection. After endometrial resection, the women were allocated to 1
of 3 groups: Group A- placebo; Group B - high-dose danazol (600 mg daily); Group
C - low-dose danazol (200 mg daily) plus placebo tablets. Tablets were
specifically manufactured for the study, were identical in appearance, and were
supplied in individual prepackaged boxes. The duration of treatment was 3 months
and patients' compliance was noted. Amenorrhoea, dysmenorrhoea and premenstrual
tension symptoms were assessed for each group by 1 or 2 independent
gynaecologists at follow-up intervals of 6 weeks, 3, 6 and 12 months. A
statistically-significant increased rate of amenorrhoea was found in patients who
received treatment with the higher-dose danazol (600 mg day) following
endometrial resection. While not statistically significant, the same trend was
noted with the low-dose danazol. This result should influence our clinical
management of women with menorrhagia, and the long-term results on the same
cohort of patients are awaited with interest.
PMID- 9653865
TI - Microlaparoscopy for suspected pelvic pathology--a comparison of 2mm versus 10mm
laparoscope.
AB - This study presents an independently-assessed comparison of the laparoscopic view
obtained using a 2mm versus 10mm laparoscope in women with suspected pelvic
pathology. Fifteen female volunteers booked for laparoscopy with clinical
evidence of pelvic abnormality according to clinical findings and/or pelvic
ultrasound were recruited for this study. Sequential observations were carried
out by independent observers for clinically significant differences. Although
discrepancies were noted in 3 patients the view obtained with the 2mm
microendoscope was considered to be comparable to that obtained with the 10mm
telescope. The cases with discordant findings included mild or minimal
endometriosis and distal tubal disease. The results of this study suggest that
microendoscopy is likely to be entirely adequate for many routine laparoscopic
procedures and sterilization.
PMID- 9653866
TI - Fetal brain death syndrome--a case report and literature review.
AB - This case describes a new feature of fetal brain death syndrome, abnormal
movements mimicking fetal convulsions being subsequently found to be decerebrate
hypertonicity in a brain-dead fetus. It also confirms the diagnostic criteria of
fetal brain death, both clinical and ultrasonic. The development of
polyhydramnios both prior to and after the presumed neurological event is
suggested as an association with the diagnosis of fetal brain death. Increased
awareness of this event and the heterogeneity of the presentation may prevent
further unnecessary Caesarean sections, as to date only 4 of the 10 cases in the
literature were diagnosed prenatally. Utilization of techniques such as fetal
blood sampling should be considered to further delineate the diagnosis.
PMID- 9653867
TI - Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.
AB - Eating disorders and the associated behavioural problems and drug abuse are
uncommon in pregnancy. When they do occur they are often unrecognized because of
denial but when significant may pose a risk to both the mother and her fetus.
This case illustrates a number of problems that may be encountered in women with
eating disorders in pregnancy, including prolonged and recurrent metabolic
disturbances and diuretic abuse. In particular it illustrates the derangements of
thyroid function seen in pregnant women with eating disorders and reminds us that
when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be
considered and explored.
PMID- 9653868
TI - A case report of Sheehan syndrome presenting with diabetes insipidus.
AB - Hypopituitarism caused by necrosis of the physiologically enlarged pituitary
gland of pregnancy following postpartum haemorrhage was first described by
Sheehan (1). Although manifestations of the clinical syndrome are most often
caused by deficiencies of hormones of the anterior pituitary gland, involvement
of the posterior lobe of the pituitary gland although rare has been described
(2,3). This is a report of a case of diabetes insipidus developing within 24
hours postpartum in a grand multipara who had an elective lower segment Caesarean
section for twins.
PMID- 9653869
TI - Successful pregnancy in a patient with previous bladder exstrophy.
AB - Bladder exstrophy is an unusual congenital anomaly. Patients becoming pregnant
with such anomaly after surgical repair are even rarer. The present case reports
a lower segment Caesarean section delivery of a living healthy baby in a woman
who had been operated on for bladder exstrophy at the age of 18 years. This is
the first case of this type seen in our institution in 35 years.
PMID- 9653870
TI - A case of transvaginal evisceration.
AB - We present a case of spontaneous evisceration of the small bowel through the
vaginal vault in a 61-year-old women. The predisposing factors and management are
discussed.
PMID- 9653871
TI - Strangulation of the small intestine: a late complication of ventrosuspension.
PMID- 9653872
TI - Assessment and management of female urinary incontinence--a survey of current
practice.
AB - A survey of conference delegates attending the Urogynaecology Day at the 1997
Annual Scientific Meeting of the Royal Australasian College of Surgeons indicated
that practitioners are inconsistent in their approach to the use of preoperative
urodynamics evaluation for women with stress incontinence and disagree about the
significance of the low pressure urethra.
PMID- 9653873
TI - The use of gemeprost pessaries to arrest postpartum haemorrhage.
PMID- 9653874
TI - Effects of S-8510, a novel benzodiazepine receptor partial inverse agonist, on
basal forebrain lesioning-induced dysfunction in rats.
AB - We investigated the effects of a novel benzodiazepine partial inverse agonist, S
8510 (2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo [4,5-d] pyrano [4,3-b] pyridine
monophosphate monohydrate), on the impairment of spatial memory, decreased high
affinity choline uptake and acetylcholine release in basal forebrain-lesioned
rats. S-8510 (3 and 5 mg/kg, p.o. 30 min before each training session)
significantly ameliorated the basal forebrain-lesion-induced impairment of
spatial memory in water maze task. In vivo brain microdialysis studies showed
that systemic administration of S-8510 at 3 and 10 mg/kg significantly increased
the release of acetylcholine in the front-parietal cortex in basal forebrain
lesioned rats. Further, repeated administration of S-8510 (3 and 10 mg kg(-1)
day(-1) for 5 days) reversed the decrease in cortical high-affinity choline
uptake induced by basal forebrain lesion. Thus, S-8510 improved the spatial
memory impairment induced by lesion of the basal forebrain in rats. In addition,
it increased acetylcholine release and high-affinity choline uptake from the
cortex, a region closely associated with memory, in basal forebrain-lesioned
rats. These results indicate that S-8510 has cognition enhancing and cholinergic
activating effects in the basal forebrain-lesioned rats, suggesting that this
agent may be useful for the treatment of mild to moderate senile dementia
including Alzheimer's disease.
PMID- 9653875
TI - Differential effects of selective adenosine A1 and A2A receptor agonists on
dopamine receptor agonist-induced behavioural responses in rats.
AB - The effects of the systemic (i.p.) administration of the selective adenosine A1
receptor agonist N6-cyclopentyladenosine (CPA) and the selective adenosine A2A
receptor agonist sodium 2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine
(CGS 21680) on different dopamine receptor agonist-induced behaviours were
studied in the male rat. CGS 21680 (1 micromol/kg), but not CPA, was found to
counteract the stereotypies induced by the non-selective dopamine receptor
agonist apomorphine (0.25 mg/kg s.c.). Low doses of CGS 21680 (0.1 micromol/kg)
and high doses of CPA (3 micromol/kg) counteracted yawning induced by the
dopamine D2 selective agonist quinpirole (0.05 mg/kg). On the other hand, low
doses of CPA (0.3 micromol/kg) antagonized grooming induced by the selective
dopamine D1 receptor-selective agonist SKF 38393 (10 mg/kg i.p.), while CGS 21680
was ineffective. These results are consistent with the proposed existence of a
selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1
and A2A receptors, respectively. The ability of CGS 21680 to counteract
apomorphine-induced stereotypies is weaker compared to its previously reported
antagonistic effect of amphetamine-induced motor activity. This supports the
hypothesis that adenosine A2A receptor agonists may be potential antipsychotic
drugs with a low potential for extrapyramidal side effects.
PMID- 9653876
TI - Footshock-induced rise of rat blood histamine depends upon the activation of
postganglionic sympathetic neurons.
AB - We have previously shown the existence of a novel peripheral reflex inhibitorily
modulating the vas deferens sympathetic activity. An interaction between
noradrenergic and histamine-containing neurons is involved in this reflex. As an
overall mechanism of sympathetic autoregulation, we found that enhanced
sympathetic activity in the rat during the stress induced by brief inescapable
footshocks caused a marked rise of blood histamine that was seemingly dependent
upon sympathetic activity. This rise was prevented by either previous ganglionic
blockade with hexamethonium or chronic guanethidine-induced sympathectomy.
Previous adrenal demedullation did not impair this rise. Thus, it appears that
only the sympathetic postganglionic neuron, interacting with a histamine
containing neuron, is involved in the rise of blood histamine induced by
footshocks.
PMID- 9653877
TI - Inflammation alters the effects of mGlu receptor agonists on spinal nociceptive
neurones.
AB - Several types of metabotropic glutamate receptor are known to be located in the
spinal cord. This study examined the effects of the metabotropic glutamate
receptor agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)
ACPD), (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) and (1S,3S)-1
aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD) on the electrically evoked
responses of dorsal horn neurones recorded in normal animals and in animals 3 h
after the induction of carrageenan inflammation. The group I and II agonist
(1S,3R)-ACPD produced facilitations of the noxious evoked neuronal responses in
normal animals, but inhibited these responses following carrageenan inflammation.
The group II agonist (1S,3S)-ACPD also produced inhibitions in the carrageenan
animals, in contrast to the mixed effects seen in normal animals. The group I
agonist (S)-3,5-DHPG produced mixed effects (inhibitions and facilitations) in
both normal and carrageenan animals. This in vivo study shows that the effects of
metabotropic glutamate receptor agonists are more complex than in vitro studies
have suggested to date.
PMID- 9653878
TI - Adenosine A2 receptor mediation of pre- and postsynaptic excitatory effects of
adenosine in rat hippocampus in vitro.
AB - Excitatory effects of adenosine in the rat hippocampus were studied by
intracellular recording from CA1 pyramidal cells in vitro. Application of 100
microM adenosine induced a rapid hyperpolarization and a decrease in input
resistance, and depressed the excitatory postsynaptic potentials (EPSPs) evoked
by stimulation of Schaffer collaterals in all neurons tested. In 55% of the
neurons this was followed by an excitation. This excitation consisted of a slow
depolarization lasting 9 +/- 4.7 min, an increase in input resistance and an
increase in the amplitude of the evoked EPSPs. This excitation could also be
observed when synaptic transmission was prevented by 1 microM tetrodotoxin
(tetrodotoxin). In the presence of 5 microM 8-(p-sulphophenyl)theophylline (8
SPT) adenosine (10 microM) enhanced the amplitude of evoked EPSPs by 20% +/- 3.6
(n = 5) in all neurons tested. Chloroadenosine (chloroadenosine; a stable analog
of adenosine; 20 microM) induced a similar hyperpolarization associated with
decrease in input resistance; this was followed by a similar excitation as seen
with adenosine in 22 of the 27 neurons tested. L-baclofen (20 microM) induced a
hyperpolarization associated with decrease in input resistance in all six neurons
tested but an ensuing excitation was not observed. CGS 21680 (30 nM), a selective
adenosine A2 receptor agonist, induced a slow depolarization associated with an
increase in input resistance and, in 11 of 36 neurons, enhanced the amplitude of
evoked EPSPs. These excitatory effects of CGS 21680 were blocked by the selective
adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX, 10
microM). In the presence of 1 microM tetrodotoxin 30 nM CGS 21680 still produced
a slow depolarization and an increase in input resistance. In addition, high
doses of CGS 21680 (10 and 20 microM) depressed the amplitude of EPSPs evoked by
stimulation of Schaffer collateral afferents, yet there was little effect on the
resting membrane potential or input resistance despite the fact that 20 microM
chloroadenosine caused a pronounced hyperpolarization associated with a decrease
in input resistance in the same cell. These results indicate that the excitatory
effects of adenosine may be mediated via activation of adenosine A2 receptors at
both presynaptic and postsynaptic sites in the hippocampal CA1 region.
PMID- 9653879
TI - Neuroprotection by novel antagonists at the NMDA receptor channel and glycineB
sites.
AB - Glutamate may act via an N-methyl-D-Aspartate (NMDA)-sensitive receptor site to
destroy cholinergic neurons within the nucleus basalis magnocellularis in age
associated neurodegenerative diseases. Multiple interesting properties of the
NMDA receptor are relevant to its excitotoxic actions, e.g., glutamate is
ineffective unless a glycine (gly) modulatory site is also occupied. Thus, the
antagonism of glutamate receptor-related toxicity by blockade of either the NMDA
sensitive recognition site or the gly binding site may therefore have therapeutic
applications. The current study investigated the ability of four novel
noncompetitive antagonists at these two sites: one NMDA open channel antagonist
(MRZ 2/579: 1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride), and three
glyB receptor antagonists (MRZ 2/570: 8-bromo-4-hydroxy-1-oxo-1,2
dihydropyridaziono [4,5-beta] quinoline-5-oxide choline salt; MRZ 2/57: 8-fluoro
4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5-oxide choline; MRZ
2/576: 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5
oxide choline) administered acutely, to provide neuroprotection from a NMDA
receptor agonist within the nucleus basalis magnocellularis of young rats.
Injection of NMDA into the nucleus basalis magnocellularis significantly
decreased cortical choline acetyltransferase activity. Acute administration
(i.p.) of MRZ 2/579, 2/570, 2/571 and 2/576 provided significant neuroprotection
from NMDA.
PMID- 9653880
TI - Presynaptic mGlu1 type receptors potentiate transmitter output in the rat cortex.
AB - In the present study we used freely moving rats with a microdialysis probe placed
in their parietal cortex to study the effects of local application of agonists
and antagonists of metabotropic glutamate (mGlu) receptors on glutamate release.
(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 0.1-1 mM), a non
selective agonist of metabotropic glutamate (mGlu) receptors, increased glutamate
concentration in the dialysate up to 3-fold. A significant increase in glutamate
output in cortical dialysates was also obtained with (RS)-3,5
dihydroxyphenylglycine (DHPG; 0.5-1 mM), a group 1-selective mGlu receptor
agonist, suggesting the involvement of group 1 mGlu receptors in 1S,3R-ACPD
effects. S-4-carboxyphenylglycine (S-4CPG; 0.3 microM), a mGlu1 receptor
antagonist with a mild agonist action on mGlu2 receptors, antagonised, in a
surmountable manner, the effects of 1S,3 R-ACPD. Similarly, 1-aminoindan-1,5
dicarboxylic acid (AIDA; 0.03-1 mM) a selective group 1 antagonist with a
preferential action on mGlu1 type receptors, antagonised the effects of 1S,3R
ACPD. Finally, (S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)-glycine (UPF596; 30-300
microM), a potent mGlu1 antagonist with modest agonist activity on mGlu5,
antagonised 1S,3R-ACPD-induced glutamate release. In conclusion, our data showed
that 1S,3R-ACPD-induced glutamate release in the parietal cortex is mediated by
mGlu1 receptors and that, under basal conditions, these receptors are not
tonically activated.
PMID- 9653881
TI - The gamma-aminobutyric acid uptake inhibitor NO-711 potentiates 3
aminopropylphosphinic acid-induced actions in rat neocortical slices.
AB - In rat neocortical slices maintained in Mg2+-free Krebs medium, the GABAB
receptor agonists baclofen and 3-aminopropylphosphinic acid dose-dependently
reduced the frequency of spontaneous discharges, 3-aminopropylphosphinic acid
being 10 times less potent than baclofen. These were sensitive to the antagonist
CGP 52432 (3-[[3,4-dichloro-phenyl)methyl]-amino]propyl](-P-diethoxymethyl)-
phosphinic acid) (1, 5 and 10 microM). The GABA uptake inhibitor NO-711 (1-(2
(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-+ ++pyridinecarboxylic
acid) (5 and 10 microM) produced 2.9 and 9 fold increases in the potency of 3
aminopropylphosphinic acid without affecting baclofen-induced responses. In this
study, the low potency of 3-aminopropylphosphinic acid when compared to baclofen,
may be attributed to its uptake by NO-711-sensitive GABA transporters.
PMID- 9653882
TI - Alpha2-adrenoceptor antagonists enhance responses of dorsal horn neurones to
formalin induced inflammation.
AB - Intrathecally applied alpha2-adrenoceptor antagonists atipamezole, idazoxan and
yohimbine had no significant effect on any neuronal response in normal animals.
In contrast, all three antagonists (100 microg) significantly increased the area
under the curve of the total response to formalin, especially the second phase.
Our results suggest the alpha2-adrenoceptor-mediated noradrenergic inhibitory
system in the spinal cord is dormant under normal conditions, but controls both
the magnitude and duration of the neuronal responses to subcutaneous injection of
formalin.
PMID- 9653883
TI - Vasopressin mediates the inhibitory effect of central angiotensin II on
cerebrospinal fluid formation.
AB - Angiotensin II infused at low doses into the cerebral ventricles decreases
cerebrospinal fluid (CSF) production. Since central angiotensin II also activates
the sympathetic nervous system and promotes vasopressin release, the roles of
these two factors in mediating the inhibitory effect of angiotensin II on CSF
formation were studied. CSF production was measured in rats by the
ventriculocisternal perfusion method. During central angiotensin II infusion (5
pg min(-1)), the following adrenoceptor antagonists were administered
intravenously (i.v.): phentolamine (alpha1/alpha2, 2 mg/kg per h), prazosin
(alpha1, 1 mg/kg per h), and propranolol (beta, 1 mg/kg per h). None of these
agents affected the inhibitory effect of angiotensin II on CSF formation. In
comparison, in animals administered i.v., the vasopressin V1 receptor antagonist,
d(CH2)5Tyr(Me)Arg-vasopressin (10 microg/kg per h), the angiotensin II-induced
decrease in CSF production was abolished. Our observations indicate, therefore,
that vasopressin mediates the inhibitory effect of central angiotensin II on CSF
formation.
PMID- 9653884
TI - In vivo microdialysis study of (+/-)-kavain on veratridine-induced glutamate
release.
AB - This is the first microdialysis study to address the effects of (+/-)-kavain on
veratridine-induced glutamate release in freely moving rats. (+/-)-Kavain (100
mg/kg, p.o.) significantly reduced veratridine-induced glutamate release compared
with that of vehicle-treated controls. Maximum extracellular glutamate levels
were obtained 20-40 min after veratridine stimulation (500 microM, added to the
perfusate). In the control group the increase was 301% and in the (+/-)-kavain
group the increase was significantly reduced to 219% (the basal value was 100%).
These results demonstrate that (+/-)-kavain reduces veratridine-induced glutamate
release in vivo, which confirms previous in vitro data.
PMID- 9653885
TI - Involvement of nitrosothiols, nitric oxide and voltage-gated K+ channels in
photorelaxation of vascular smooth muscle.
AB - The effects of nitrosothiol depleting compounds (p-hydroxymercuribenzoate,
iodacetamide and ethacrynic acid), a guanylyl cyclase inhibitor
(1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and nitric oxide (NO) scavenger
agents (xanthine/xanthine oxidase and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl
imidazoline-1-oxyl-3-oxide; carboxy-PTIO) on light-induced photorelaxation in rat
thoracic aorta were investigated. Photorelaxation responses were decreased in the
presence of nitrosothiol depleting compounds suggesting S-nitrosothiols as the
tissue source of the NO, whereas reduction in photorelaxation by the guanylyl
cyclase inhibitor and NO scavenger agents indicates involvement of both NO and
cGMP in photorelaxation. In addition the sensitivity of photorelaxation to the
voltage-gated potassium channel (KV) inhibitor, 4-aminopyridine, indicates that
photorelaxation is mediated via a NO/cGMP-dependent, and, perhaps, direct light,
activation of KV channels.
PMID- 9653886
TI - Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats.
AB - This study was undertaken to determine the extent to which nitric oxide (NO)
mechanisms are involved in cerebral hyperemia following global brain ischemia.
The vertebral arteries were cauterized through the first alar foramina in
anesthetized male Sprague-Dawley rats and followed by 20-min occlusion of the
common carotid arteries. Blood flow from the parietal cerebral cortex was
measured using laser-Doppler flowmetry. In saline-treated animals, carotid
occlusion reduced cerebral blood flow by approximately 95% with a maximal
hyperemia of about 400% observed after 15 min of reperfusion. Pre-treatment with
the nonspecific NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester;
2, 10 and 50 mg kg(-1)), produced dose-related depression of post-ischemic
hyperemia, whereas D-NAME (10 mg kg(-1)) was inactive. Pre-treatment with L
arginine (300 mg kg(-1), i.v.) prevented L-NAME attenuation of cerebral
hyperemia. The selective neuronal NO synthase inhibitor, 7-nitroindazole (30 mg
kg(-1)), was without significant depressant effect. These results suggest that NO
(largely from vascular endothelium) is instrumental in development of post
ischemic cerebral hyperemia.
PMID- 9653887
TI - Relationship between the antithrombotic effect of YM-75466, a novel factor Xa
inhibitor, and coagulation parameters in rats.
AB - The relationship between the antithrombotic effects of intravenous infusions of
YM-75466 [N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-naph
thyl)methyl] sulfamoyl]acetic acid monomethanesulfonate), a novel factor Xa (FXa)
inhibitor, and various coagulation parameters (prothrombin time, activated
partial thromboplastin time, thrombin-antithrombin III complex (TAT), anti-FXa
activity and anti-thrombin activity) in rats was studied and compared with
results for heparin. In the arterio-venous shunt model, both agents exerted
antithrombotic effects in a dose-dependent manner. Coagulation parameters were
studied simultaneously with antithrombotic effects. YM-75466 did not prolong
coagulation time even at the dose which exerted significant antithrombotic
effects, while it decreased TAT level in plasma in a dose-dependent manner. YM
75466 exerted anti-FXa activity but not anti-thrombin activity. In contrast,
heparin prolonged activated partial thromboplastin time in a dose-dependent
manner and decreased TAT level in plasma with increasing inhibition of thrombus
formation. Heparin exerted both anti-FXa and anti-thrombin activity in a dose
dependent manner. These results suggest that TAT is a suitable parameter for
monitoring the antithrombotic effect of YM-75466 in the arterio-venous shunt
model in rats and that YM-75466, unlike heparin, exerts its antithrombotic effect
through specific inhibition of FXa without any effect on thrombin.
PMID- 9653888
TI - Histamine receptor subtypes mediating hyperpolarization in the isolated, perfused
rat mesenteric pre-arteriolar bed.
AB - Histamine is a general dilator of rat blood vessels. We investigated the relative
contribution of receptor subtypes to the rat mesenteric dilator responses
initiated by histamine and related agonists. Histamine initiated dose, and
endothelium-dependent, dilation of constricted mesenteric beds with an ED50 of
0.4 +/- 0.1 nmol. The ED50 was increased 10-fold by 0.1 microM chlorpheniramine
(a histamine H1-receptor selective antagonist). Histamine H2 receptor blockade
with tiotidine (0.1 microM) slightly decreased, while thioperamide (1 microM), a
selective histamine H3 receptor antagonist, did not block histamine-induced
dilation. Mesenteric bed dilation initiated by histamine H2 receptor selective
agonists, amthamine and dimaprit, were antagonized markedly by tiotidine.
However, the dilation initiated by the putative histamine H3 receptor selective
agonists, R(-)- or S(+)-alpha-methylhistamine and imetit were not affected by
thioperamide (1 microM). Histamine H2- and H3-receptor mediated dilator effects
were endothelium-independent and were blocked by either excess (80 mM)
extracellular K+, or 1 mM tetrabutylammonium (a non-selective K+ channel
blocker), as well as by 1 microM dequalinium, a non-peptide blocker of the small
conductance Ca2+-activated (SKCa) K+ channels. We conclude that (i) histamine H1
receptor subtype predominantly mediates endothelium-dependent dilator effect of
histamine, and (ii) vascular hyperpolarization through opening of K+ channels
(SKCa) mediate the dilator responses to histamine H2 receptor (amthamine and
dimaprit) and the putative histamine H3 receptor (R(-)-alpha-methylhistamine and
imetit) agonists.
PMID- 9653889
TI - Acute and chronic neutral endopeptidase inhibition and the natriuretic response
to acute volume expansion.
AB - Neutral endopeptidase inhibition (NEPI) provides a potential avenue to modulate
the actions of atrial natriuretic peptide (ANP). We tested the hypothesis that
acute and chronic NEPI increased the renal responses at baseline and after acute
volume expansion in rats. ANP plasma levels and cGMP excretion were significantly
increased with acute NEPI by SQ 28.603, whereas chronic inhibition with SCH 34826
did not lead to any changes. The ratio of cGMP excretion per plasma ANP, however,
was significantly increased (6.2 +/- 0.9) by chronic treatment with SCH 34826
compared to chronic vehicle treatment (4.2 +/- 0.7) indicating an activated renal
ANP receptor system. Baseline diuresis and natriuresis were enhanced with acute
but not with chronic treatment. After acute volume expansion, ANP increased five
fold with acute NEPI, whereas it only increased about 70% in chronically
inhibited rats. The natriuretic (497 +/- 62 vs. 329 +/- 42 micromol/60 min with
vehicle, P < 0.05) and diuretic responses were significantly enhanced with
chronic treatment. Together with an increased cGMP/ANP ratio, these data suggest
that chronic activation of the renal ANP system after long-term NEPI facilitated
the excretion of an acute volume load. These findings may have therapeutic
implications in patients with chronic sodium retention.
PMID- 9653890
TI - Antitussive effect of moguisteine on allergic coughs in the guinea pig.
AB - The effect of moguisteine, a novel peripherally acting non-narcotic antitussive
drug, on allergic coughs was examined in guinea pigs. Male Hartley guinea pigs
were actively sensitized to ovalbumin. The number of coughs elicited over 5 min
following a 2-min exposure to ovalbumin was counted. Exposure of sensitized
guinea pigs to 0.5% ovalbumin aerosol induced 22.0 +/- 3.2 coughs/5 min.
Moguisteine at doses of 30 and 56 mg/kg, p.o., dose-dependently and significantly
suppressed the number of allergic coughs. Dihydrocodeine at doses of 30 and 56
mg/kg, p.o., dose-dependently but not significantly reduced the number of
allergic coughs. These results suggest that moguisteine may be of a therapeutic
benefit in reducing allergic coughs.
PMID- 9653891
TI - Airway hyperresponsiveness to histamine in mycoplasmal infection: role of
histamine N-methyltransferase.
AB - To elucidate the modulatory role of histamine-degrading enzymes in airway
constrictor responses in mycoplasmal infection, we studied hamster tracheal
segments under isometric conditions in vitro. Nasal inoculation with Mycoplasma
pneumoniae potentiated the contractile responses to histamine but not to
methacholine. Pretreatment of tissues with the histamine N-methyltransferase
inhibitor SKF 91488 abolished the infection-induced potentiation, whereas, the
diamine oxidase inhibitor aminoguanidine had no effect. The histamine N
methyltransferase but not diamine oxidase activity in tracheal tissues was
decreased in infected animals. These results suggest that M. pneumoniae causes
airway hyperresponsiveness to histamine probably through a reduction of
endogenous histamine N-methyltransferase activity.
PMID- 9653892
TI - Capsaicin treatment induces muscarinic hyperreactivity in guinea pig trachea: a
warning.
AB - Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a widely used tool for the
depletion of neuropeptides from sensory C-fibres. Upon capsaicin treatment
tachykinins are released, resulting in a variety of responses in the airways. We
showed that after capsaicin (0.3 microM; 30 min) treatment of guinea pig tracheal
smooth muscle preparations, the maximal contraction of the trachea after
methacholine stimulation was strongly increased (capsaicin: 1.147 +/- 0.050 g vs.
control: 0.717 +/- 0.047 g). This effect was completely nullified after
pretreatment with capsazepine (2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8
dihydroxy-2,3, 4,5-tetrahydro-1H-2benzazepine; a vanilloid receptor antagonist)
and YM38336 (a dual tachykinin NK1 and tachykinin NK2 receptor antagonist). Our
results serve as a warning against using capsaicin as a putatively clean
pharmacological tool to deplete the neuropeptides from pools on the C-fibres
because we showed that capsaicin also strongly influences basal mechanisms in
tracheal smooth muscle control.
PMID- 9653893
TI - Effects of ZD7114, a selective beta3-adrenoceptor agonist, on neuroendocrine
mechanisms controlling energy balance.
AB - Selective beta3-adrenoceptor agonists increase energy expenditure by increasing
non-shivering thermogenesis in brown adipose tissue. The aim of this study was to
investigate how changes in energy balance affect energy intake and interaction of
peripheral metabolic feedback signals with central neuroendocrine mechanisms
participating in the control of body energy balance. Expression of
preproneuropeptide Y (preproNPY) mRNA in the arcuate nucleus and
preprocorticotropin-releasing factor (CRF) mRNA in the paraventricular nucleus
were measured by in situ hybridisation technique after 1 day, 1 and 5 weeks of
treatment with ZD7114 ((S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2
methoxyet hyl)phenoxyacetamide, 3 mg kg(-1) day(-1) in drinking water) in obese
fa/fa Zucker rats. In addition, expression of leptin mRNA in epididymal fat and
serum levels of leptin were analysed. Food intake, body weights, binding of GDP
to brown adipose tissue mitochondria, plasma insulin and glucose were also
measured. Treatment with ZD7114 significantly reduced weight gain and activated
brown adipose tissue thermogenesis, but had no effect on food intake. Expressions
of preproNPY or preproCRF mRNAs were similarly not changed by treatment with
ZD7114. Furthermore, ZD7114 had no effect on plasma insulin or leptin and the
expression of leptin mRNA in epididymal fat. However, statistically significant
correlations were found between preproNPY and preproCRF mRNA expressions and
brown fat thermogenic activity and plasma insulin levels in the ZD7114 treated
rats, but not in the control rats. It is concluded that treatment with ZD7114
markedly activated brown fat thermogenesis, but did not affect neuropeptide Y
(NPY) and CRF gene expression per se. However, the correlation analyses suggest
that ZD7114 may modulate feedback connections of brown adipose tissue
thermogenesis and plasma insulin with the hypothalamic neuroendocrine mechanisms
integrating body energy balance.
PMID- 9653894
TI - Effects of calcitonin gene-related peptide-(8-37) on withdrawal responses in rats
with inflammation.
AB - The present study was performed to explore the effect of subcutaneous injection
of carrageenan into the rat plantar region on hindpaw edema formation and the
latency of hindpaw withdrawal to presumed nociceptive stimulation. Subcutaneous
injection of carrageenan into the left hindpaw induced a significant increase in
the volume of the left hindpaw, leaving the right side unaffected. In addition,
we found a bilateral decrease in hindpaw withdrawal latency to heat and
mechanical, but not to cold stimulation. The decreased bilateral hindpaw
withdrawal latency to heat stimulation lasted for 14 days after carrageenan
injection. The decreased bilateral hindpaw withdrawal latency to mechanical
stimulation lasted for 2 days after the injection, then reversed and increased
from day 3 to 14. Intrathecal injection of either 10 nmol of calcitonin gene
related peptide 8-37 or 26.6 nmol of morphine induced significant bilateral
increases in hindpaw withdrawal latency, which were more pronounced with the
morphine. The results show that experimentally induced unilateral hindpaw
inflammation induces a bilateral decrease in hindpaw withdrawal latencies to
presumed nociceptive stimulation while the sensory systems for heat and
mechanical stimulation were differently affected after carrageenan injection.
PMID- 9653895
TI - Effect of hypolipidemic drugs on key enzyme activities related to lipid
metabolism in normolipidemic rabbits.
AB - The effect of atorvastatin (3 mg kg(-1) day(-1)), simvastatin (3 mg kg(-1) day(
1)) and bezafibrate (100 mg kg(-1) day(-1)) administered for 4 weeks to male New
Zealand white rabbits on enzyme activities related to lipid metabolism has been
studied. Only the statins reduced plasma cholesterol values, while none of the
drugs modified plasma triglyceride or high density lipoprotein (HDL)-cholesterol
concentrations, nor the activity of enzymes such as hepatic diacylglycerol
acyltransferase, lipoprotein lipase or hepatic lipase, directly involved in
triglyceride metabolism. Both statins elicited similar increases in the hepatic
microsomal 3-hydroxy-3-methyl-glutaryl Coenzyme A (CoA) reductase activity (147
and 109% induction for simvastatin and atorvastatin, respectively), and none of
the drugs assayed modified hepatic acyl-coenzyme A:cholesterol acyltransferase
activity significantly. Only bezafibrate induced a significant 57% reduction in
the activity of hepatic microsomal cholesterol 7alpha-hydroxylase. Regarding the
rate limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine
cytidylyl transferase, atorvastatin and bezafibrate behaved similarly, decreasing
the enzyme activity in the liver by 45% and 54%, respectively; simvastatin
induced no modification of this activity. The reduction of CTP:phosphocholine
cytidylyl transferase activity is not caused by a direct inhibition of the enzyme
by bezafibrate and atorvastatin. Further, the inhibitory effect of atorvastatin
appears to be unrelated to the inhibition of 3-hydroxy-3-methyl-glutaryl CoA
reductase elicited in vivo.
PMID- 9653896
TI - Are high-affinity progesterone binding site(s) from porcine liver microsomes
members of the sigma receptor family?
AB - Membrane progesterone binding sites have been purified recently from pig liver.
Since progesterone is considered as an endogenous sigma (sigma) receptor ligand,
these sites were characterized pharmacologically by ligands selective for sigma
receptor and dopamine receptor binding sites, and by other drugs from distinct
pharmacological classes. Binding studies using the radioligand [3H]progesterone
were done in crude membrane preparations and solubilized fractions to determine
half-maximal inhibitory concentration (IC50) values, from which inhibitory
constants (Ki values) were calculated. Radioligand binding was inhibited by the
sigma receptor ligands haloperidol, carbetapentane citrate, 1,3-Di(2
tolyl)guanidine (DTG), R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2 aminopropane HCl (R(
)-PPAAP HCl), or sigma receptor antagonists like (+)-3-(3-hydroxyphenyl)-N
propylpiperidine HCl (R(+)-PPP HCl) and cis-9-[3-(3,5-dimethyl-1
piperazinyl)propyl]-9H-carbazole dihydrochloride (rimcazole 2HCl). The hierarchy
of inhibitory action was not fully compatible with either sigma receptor class I
(moderate affinity of pentazocine, diphenylhydantoin (phenytoin) insensitivity)
or II sites (high affinity of carbetapentane). The data thus suggest that
progesterone binding sites in porcine liver membranes are related to the sigma
receptor binding site superfamily, but may represent a particular species with
progesterone specificity.
PMID- 9653897
TI - Characterization of alpha1-adrenoceptor subtypes in the pig.
AB - The identities of the alpha1-adrenoceptor subtypes present in various tissues of
the pig were studied using [3H]prazosin radioligand binding. The subtypes were
characterized by performing competition experiments for various subtype selective
drugs. In the cerebral cortex, spleen and heart, both alpha1A- and alpha1B
adrenoceptors were detected. In the liver was found only the alpha1A-subtype,
while in the aorta was found only the alpha1B-subtype. An alpha1-adrenoceptor
subtype was present in the adrenal gland with a high affinity for prazosin, the
pKd value being 9.6, but with relatively low affinities for other alpha1
adrenoceptor binding drugs. The adrenal gland alpha1-adrenoceptor did not seem to
represent the classical alpha1D-subtype, since drugs selective for the alpha1D
subtype in other species, including BMY7378 and SKF104856, showed low affinities
for the pig adrenal gland alpha1-adrenoceptor.
PMID- 9653898
TI - Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA
receptors.
AB - Recent pharmacological studies indicate that aminoglycoside-induced hearing loss
may be an excitotoxic process modulated by a polyamine-like activation of
cochlear NMDA receptors. Aminoglycoside antibiotics are constituted by a series
of glycosidically linked aminocyclitols and aminosugars. We report here on the
actions of these individual aminocyclitols and aminosugars on wild type NMDA
receptors from rat brain. Compared to the parent molecules, neither
aminocyclitols (e.g., 2-deoxystreptamine, streptamine, and streptidine) nor
aminosugars (e.g., D-glucosamine and kanosamine) were effective at enhancing
[3H]dizocilpine ([3H]MK-801) binding or inhibiting [3H]ifenprodil at NMDA
receptors. Moreover, the appropriate combinations of aminosugars and
aminocyclitols did not reconstitute the activity of the parent aminoglycoside at
NMDA receptors. These data indicate that the polyamine-like actions of
aminoglycosides are attributable to the conformation of the parent molecule
rather than a particular amine containing constituent. Thus, it may be possible
to synthesize or isolate aminoglycoside antibiotics devoid of ototoxicity.
PMID- 9653899
TI - Kinetics of alkylation of cloned rat alpha1-adrenoceptor subtypes by
chloroethylclonidine.
AB - We quantified and compared the rates at which chloroethylclonidine (CEC)
inactivated cloned rat alpha1A, alpha1B-, and alpha1D-adrenoceptors. Membranes
from cells transfected with one of the three cloned alpha1-adrenoceptors were
incubated for various intervals with 100 microM chloroethylclonidine at 10
degrees C, 25 degrees C or 37 degrees C. The fraction of receptors alkylated by
chloroethylclonidine was determined by [3H]prazosin binding. Chloroethylclonidine
fully inactivated each alpha1-adrenoceptor subtype via a first order reaction.
Alkylation by chloroethylclonidine was markedly slower for the alpha1A
adrenoceptor vs. the other two subtypes (rate constants in 10(-3) min(-1) at 10
degrees C: 0.99 +/- 0.01 (alpha1A), 7.26 +/- 0.15 (alpha1B), and 7.01 +/- 0.12
(alpha1D)). Despite differences in rate, activation energies for alkylation were
similar among subtypes. suggesting a similar binding sites for
chloroethylclonidine. Computer simulations of kinetic data in mixed receptor
populations and experiments with membranes from rat brain showed that nonlinear
curve fitting could distinguish relative proportions of alpha1A-adrenoceptor vs.
the other two subtypes. We conclude that measurement of the rate of alkylation by
chloroethylclonidine, rather than the total amount of alkylation, is most useful
in distinguishing the relative proportion of alpha1A-adrenoceptor in tissues.
PMID- 9653900
TI - Pericardial mesothelial cells produce endothelin-1 and possess functional
endothelin ETB receptors.
AB - We investigated the endothelin production and endothelin receptor activity of
pericardial mesothelial cells obtained from spontaneously hypertensive rats (SHR)
and Wistar-Kyoto (WKY) rats. The pericardial mesothelial cells were maintained in
vitro and the production of endothelin-1 by these cells was evaluated by using a
sensitive sandwich-type enzyme immunoassay for endothelin-1 and big endothelin-1.
Endothelin receptor subtypes were pharmacologically analyzed by measuring the
changes of intracellular Ca2+ concentration ([Ca2+]i) in pericardial mesothelial
cells. Mesothelial cells from both strains produced more immunoreactive
endothelin-1 than big endothelin-1. The production of immunoreactive endothelin-1
progressively increased in a culture time-dependent manner. The amount of
immunoreactive endothelin-1 detected after 72 h in pericardial mesothelial cells
of SHR was significantly (P < 0.05) higher than that in the cells of WKY rats
(SHR: 196.7 +/- 19.1 pg/10(6) cells; WKY: 122.7 +/- 10.6 pg/10(6) cells).
Endothelin-1 and endothelin-3 induced elevation of [Ca2+]i in pericardial
mesothelial cells. The selective agonist of the endothelin ETB receptor,
sarafotoxin S6c, also induced elevation of [Ca2+]i. The endothelin- and
sarafotoxin S6c-induced elevations of [Ca2+]i in pericardial mesothelial cells
from SHR were greater than those in mesothelial cells from WKY rats. The
endothelin ETB receptor antagonist, IRL 1038 ([Cys11,Cys15]endothelin-1-(11-21)),
significantly inhibited the endothelin-1- and endothelin-3-induced changes in
[Ca2+]i. The endothelin ETA receptor antagonist, FR 1393171 ((R)2-[(R)-2-[(S)-2
[[1-(hexahydro-1H-azepinyl)]carbonyl]ammino -4-methylpentanoyl]amino-3-[3-(1
methyl-1H-indoyl)]propio nyl]amino-3-(2-pyridyl)propionic acid), did not affect
these changes. From these results, pericardial mesothelial cells from both SHR
and WKY rats shared the ability to produce endothelin-1 spontaneously in culture,
although consistently greater production was detected in cultures of SHR origin.
Moreover, pericardial mesothelial cells of SHR origin may have increased numbers
of endothelin ETB receptors and/or a more active signal transduction system
compared with those of WKY rats. These results suggest that endothelin-1 may play
an important role in the pericardium in an autocrine and/or paracrine fashion.
PMID- 9653901
TI - Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen
activated protein kinase activity in rat aorta.
AB - We measured the activity of mitogen-activated protein (MAP) kinases, enzymes
believed to be involved in the pathway for cell proliferation, in rat aortic
strips with or without endothelium, and examined effects of angiotensin receptor
antagonists, endothelin receptor antagonists and nitric oxide (NO)-related
agents. Endothelium removal produced an activation of MAP kinase activity in the
strips, whereas the enzyme activity was not affected in the adventitia. The MAP
kinase activation was inhibited by either the angiotensin AT1 receptor antagonist
losartan or the endothelin ETA receptor antagonist BQ 123. The combination of
both antagonists caused an additive inhibition. The angiotensin AT2 receptor
antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not
affect the MAP kinase activation. The NO synthase inhibitor NG-nitro-L-arginine
methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium
intact aorta and the MAP kinase activation was inhibited by losartan or BQ123.
The NO releaser nitroprusside inhibited the MAP kinase activation induced by
endothelium removal or angiotensin II. These results suggest that even in
isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting
effects and endogenous angiotensin II and endothelins in the media are tonically
released to cause MAP kinase-stimulating effects in medial smooth muscle.
PMID- 9653902
TI - Absence of association between delta and gamma2 subunits in native GABA(A)
receptors from rat brain.
AB - We investigated the possible association between delta and gamma2 subunits in
native GABA(A) receptors, from different rat brain regions, using subunit
specific anti-delta and anti-gamma2 antibodies. Previous reports have provided
somewhat controversial results, indicating both the presence and the absence of
association between these two subunits in native receptors. Our results indicate
the absence of co-localization between delta and gamma2 subunits. In
immunoprecipitation experiments, anti-delta antibody consistently
immunoprecipitated [3H]muscimol binding activity (GABA binding sites) from all
brain areas tested (10-20% of the total binding). However, under the same
conditions, no significant [3H]flumazenil or [3H]ethyl 8-azido-6-dihydro-5-methyl
6-oxo-4H-imidazol[1,5-a]-[1,4]benzodiazepine- 3-carboxylate (Ro15-4513) binding
(benzodiazepine binding sites) activity was detected in the immunopellets. These
results indicate the absence of association between delta and gamma2 subunits.
This question was directly addressed by immunopurification and Western blot
experiments. As expected, no gamma2 subunits were detected in anti-delta
immunoaffinity purified receptors. Conversely, no delta subunits were identified
in anti-gamma2 immunopurified receptors. Thus, these results demonstrate the
absence of association between delta and gamma2 subunits in native GABA(A)
receptors. Finally, our results also indicate the relevance of the solubilization
conditions on the apparent association between different subunits of the native
GABA(A) receptor complex.
PMID- 9653903
TI - Cyclic GMP inhibits cytoplasmic Ca2+ oscillation by increasing Ca2+-ATPase
activity in rat megakaryocytes.
AB - The regulatory effects of cyclic GMP on purinoceptor-operated cytoplasmic Ca2+
oscillation of rat megakaryocytes were investigated by using whole-cell patch
clamp technique. ATP-induced oscillatory K+ currents though Ca2+-activated K+
channels (I(KCa)S) were depressed by pretreatment with the guanylate cyclase
activator, sodium nitroprusside, and a stable membrane-permeable cGMP analogue, 8
bromo-cGMP. The inhibition by sodium nitroprusside was blocked by treatment with
a cyclic nucleotide-dependent protein kinase inhibitor, N-[2-(methylamino)]-5
isoquinolinesulfonamide x HCl (H-8) (10 microM), but not by a selective cAMP
dependent-protein kinase inhibitor, Rp-cAMPS (100 microM). The oscillatory I(KCa)
directly evoked by intracellular D-myo-inositol-trisphosphate (IP3) perfusion was
also inhibited by the application of sodium nitroprusside. The inhibitory effect
of sodium nitroprusside disappeared when the ATP-induced oscillatory I(KCa) was
changed to a monophasic sustained I(KCa) current by inhibition of Ca2+-ATPase.
These results suggested that cGMP depressed Ca2+ mobilization by improving Ca2+
ATPase activity by phosphorylation.
PMID- 9653904
TI - Foetal erythrocytes exhibit an increased ability to scavenge for nitric oxide.
AB - The presence of adult human whole blood inhibited in vitro relaxations of rat
aortic rings by the nitric oxide (NO) donor S-nitroso-N-acetyl-DL-penicillamine
(SNAP). Incubation with foetal blood containing the same concentration of
haemoglobin produced a shift to the right of the relaxation curve. SNAP-induced
vasorelaxations were more inhibited by dialysed solutions of haemoglobin than by
the presence of erythrocytes in the organ bath, but there were no differences
between the effect of adult or foetal haemoglobins. The presence of plasma from
adult or foetal blood did not modify the effects of SNAP. Relaxations induced by
endogenous, endothelium-derived, NO were more inhibited by foetal than by adult
erythrocytes. These results suggest that foetal erythrocytes have a higher NO
scavenging effect than those present in adult blood.
PMID- 9653907
TI - Human vaginal mucosal immune system: characterization and function.
AB - OBJECTIVE: The mucosal immune system has been recognized as the first line of
defense against foreign antigens. The limited information available on the
mucosal immunity of the lower reproductive organs have restricted our ability to
fight infections, especially, the sexually transmitted disease. The aim of this
study was to characterize in-vitro the human vaginal lamina propria lymphocytes
(VLPL), their cell surface phenotypes, and cellular function. METHODS: VLPL were
isolated from human vaginal mucosa by enzymatic techniques. Cell surface
characteristics were investigated by immunohistochemistry and flow cytometric
analysis. Cellular immune function was evaluated by 3H-thymidine incorporation
studies and ornithine decarboxylase (ODC) activity. RESULTS: Immunohistochemistry
and flow cytometric analysis showed that the CD4/CD8 ratio of the human vaginal
mucosa is reversed compared to the gut lamina propria lymphocytes (0.55 +/-
0.17). PHA and ConA mitogens enhanced VLPL thymidine incorporation, while PWM did
not have any significant effect. Very high level of ODC activity was observed in
VLPL after PHA stimulation. CONCLUSIONS: The human VLPL can be isolated,
characterized, and respond to a mitogenic stimulus. We postulate that further
analysis of the vaginal immune system will enhance our understanding of local
defence mechanisms which will help in the development of new therapeutic
modalities against vaginal infections.
PMID- 9653906
TI - Proliferative activity, p53 accumulation and neoangiogenesis in pulmonary
carcinosarcomas and pulmonary blastomas.
AB - Carcinosarcoma and pulmonary blastomas are rare biphasic tumors. Lung cancer
pathogenesis is a multistep process. Proliferative activity, p53 accumulation and
angiogenesis are of well-known relevance and ought to be evaluated in the
epithelial and mesenchymal components of these tumors. Using antibodies against
Ki-67 epitope MIB1 and proliferating cell nuclear antigen (PC 10) in 10
carcinosarcomas, tumors revealed a significantly higher proliferative activity in
the epithelial component compared with the mesenchymal component in the MIB1
reaction (p = 0.013). In three pulmonary blastomas of the biphasic subtype,
proliferative activity was similar in both parts. In five of 10 carcinosarcomas
and in one of three pulmonary blastomas, accumulation of the p53 epitopes Pab
1801 and/or DO-1 was found. At the tumor front, a significantly higher vessel
density was found compared with the central parts (p < or = 0.015) using a
monoclonal antibody against human endothelium (CD 31). No differences were found
between carcinosarcomas and pulmoblastomas. Higher proliferative activity in
carcinosarcomas revealed a better prognosis regarding metastasis behavior (p =
0.05) and tumor-associated death in the follow-up (p < or = 0.017). p53
accumulation and microvessel density were of no prognostic value. This is in
contrast to results in non-small cell lung cancer, pointing to a different
biologic behavior.
PMID- 9653908
TI - Prognostic assessment of histologic parameters in breast carcinomas: a
prospective study.
AB - A group of 350 unselected breast cancer patients, treated at the Center of
Oncology in Cracow, Poland, between January 1992 and December 1994, was analyzed.
The following reciprocally interrelated histologic characteristics were
evaluated: 1) histologic tumor type (considered in 3 categories of aggressivity),
2) tumor grade (according to Scarf-Bloom-Richardson), 3) constituent of in-situ
carcinoma in invasive cancers and characterization of breast lobuli, 4) tumor
growth pattern (microfocal, macrofocal or mixed), 5) invasion of nerves, 6)
vascular invasion by cancer cells in tumor surroundings, 7) extensiveness of
tumor necrosis, 8) involvement of the breast distant from the tumor mass by
cancer cells, 9) status of axillary lymph nodes, 10) invasion of metastatic lymph
node surroundings. Metastases in axillary lymph nodes were independently
influenced by vascular invasion in tumor surroundings and tumor diameter. The
disease-free survival was independently influenced by tumor diameter, necrosis
and stage of the disease (pTNM), whereas total survival related to tumor
diameter, nodal status, microfocal pattern of tumor growth, vascular invasion and
involvement of breast by cancer distant from the tumor mass was independently
influenced only by tumor stage (pTNM).
PMID- 9653909
TI - Chronic nonspecific endometritis.
AB - To assess the proliferative activity of glands and stroma in nonspecific chronic
endometritis (NCE), we evaluated the plasma and morphologic features. We examined
25 endometrial sections that were coded as inactive for the morphologic features
of NCE other than plasma cells and 25 proliferative endometria (PE) as controls.
Furthermore, the sections were stained with methyl green pyronin (MGP) to
demonstrate plasma cells and proliferative cell nuclear antigen (PCNA) for
proliferative activity. The number of plasma cells and the grade of proliferative
activity were determined by a semiquantitative scale. The results were compared
by using the Mann-Whitney-U-test. Of the 25 inactive endometria cases, 11 were
NCE and 14 were either early proliferative endometria (seven cases), lower
uterine segments (five cases), or under hormone effect (two cases). The number of
plasma cells in NCE was significantly higher than in PE. However, there were
cases of NCE without plasma cells and cases of PE containing plasma cells.
Proliferative activity was significantly lower in NCE cases than in the PE group
(p < 0.05). The diagnosis of NCE should rely more on morphologic abnormalities
than on plasma cell criteria. Identification of plasma cells may be useful for
diagnosis.
PMID- 9653910
TI - Frequency of endocervical cells in cervical smears and hysterectomy rate of the
patients.
AB - In gynecologic cytology, different reporting schemes suggest mentioning the
presence of endocervical cells or asking for a statement on adequacy. We were
interested in the question whether our data could provide a possible basis for
discussing a sampling technique with smear takers. At the time of writing, in all
cases, both the presence of endocervical cells and hysterectomy are recorded in
our laboratory information system. Most smears are taken with cotton swabs, but
the sampling technique is often modified according to the clinical situation. In
a series of 20,471 cervical/vaginal smears, 2,152 (10.5%) were taken from
hysterectomy patients. Among the non-hysterectomy patients, endocervical cells
were found in 65% of the cases. Typically, there was a lower frequency of
endocervical cells in smears stemming from older women. The frequency decreased
from a maximum of 75% in the age group of 40-44 years to 45% in the age group of
65-69 years. With regard to the smear takers, some differences were evident, with
age distribution and frequency of hysterectomy being different among the smear
takers. In a setting where many smears of hysterectomized patients are examined
by cytology, good data quality is required to evaluate the sampling techniques of
different smear takers. The age dependence of endocervical cell yield is
confirmed. Different age distribution of the patients from different smear takers
suggests that the percentage of smears showing endocervical cells cannot be
considered an optimal estimator.
PMID- 9653911
TI - Quantitative analysis of HLA DR expression and lymphocytic infiltrate in
laryngeal cancer including clinical and morphological correlations.
AB - HLA DR antigen expression in tumor cells and lymphocytic infiltrates at the
tumour periphery were investigated in 68 laryngeal carcinomas. The tissue
sections were studied by a quantitative method using computer image analysis
system. The highest number of CD45RO+ cells was observed in the groups of the
lowest clinical stage. There were statistically significant differences between
the groups in the number of T cells, whereas no differences were found in HLA DR+
cancer cell number, B cell number or mitosis count. Statistical analysis revealed
a significant correlation between T-cell number at the periphery of the tumour
and the number of cancer cells showing HLA DR expression. The results of the
analysis, using Cox proportional hazard model with selected factors, showed that
only HLA DR expression in cancer cells had a significant effect on survival,
whereas the number of CD45RO+ and CD20+ cells, histological grade and mitosis
count did not contribute further to prognostic information. To our knowledge,
this is the first time that HLA DR expression and its correlation with
lymphocytic infiltration have been shown by a quantitative method in laryngeal
cancer.
PMID- 9653912
TI - Stereological estimation of mean nuclear volume and staining pattern of Ki-67
antigen in keratoacanthomas and squamous cell carcinomas.
AB - Keratoacanthomas and squamous cell carcinomas of the skin share many
histopathologic features, making differential diagnosis difficult. The aim of
this study is to investigate the staining pattern of proliferating cells in
keratoacanthomas and squamous cell carcinomas of the skin and to evaluate the
value of nuclear morphometric criteria in differential diagnosis. Mean nuclear
volume was assessed in 21 keratoacanthomas and 21 squamous cell carcinomas in
tissue sections by a stereologic method. Immunohistochemical expression of Ki-67
monoclonal antibody was assessed and the distribution pattern (random or
peripheral) of proliferating cells evaluated. Mean nuclear volume (MNV +/- SD)
was 590 +/- 293.0 for squamous cell carcinomas and 615 + 305.9 for
keratoacanthomas. Statistical analysis showed no significant differences between
both groups (p = 0.78) in terms of mean nuclear volume values. Proliferating
cells in keratoacanthomas showed a peripheral distribution, whereas there was a
random distribution of proliferating cells in squamous cell carcinomas. Our
results indicate that quantitative nuclear features are not helpful in making a
differentiation between keratoacanthomas and squamous cell carcinomas, while
immunohistochemistry with Ki-67 antibody may give useful additional information
in differential diagnosis.
PMID- 9653913
TI - Atherosclerotic lesions, myocardial damage and lipidograms: a multiarterial study
applying an atherometric system and canonical correlation.
AB - 472 autopsy subjects were examined with the following aims: to study the
association pattern of atherosclerotic lesions between different arterial
sectors, the impact of serum lipid disorders (total cholesterol, HDL-c, LDL-c,
VLDL-c, and triglycerides were analyzed) and the association pattern between the
atherosclerotic lesions in different arterial sectors and the degree of heart
damage. For morphometric analysis of the vessels (aorta, circle of Willis,
coronary, renal, iliac, and femoral arteris) the atherometric system was used.
The most relevant results were as follows: the lipid disorders show their
greatest impact in the heart, coronary and femoral arteries and abdominal aorta,
whereas the strongest correlations between the atherosclerotic lesions in
different arterial sectors were found in those with anatomical continuity.
PMID- 9653914
TI - Primary malignant lymphoma of the kidney: case report and literature review.
AB - We report on a 65-year-old white woman who was hospitalized because of symptoms
of an acute adrenocortical insufficiency. A CT scan revealed the presence of a
large mass in the left kidney that infiltrated the adrenal gland. Fine needle
aspiration cytology of the mass under imaging control failed to achieve a correct
diagnosis, and nephrectomy was undertaken with a preoperative diagnosis of renal
cell carcinoma. However, the frozen section reveals a neoplasm of large lymphoid
cells with a diffuse growth pattern. Immunohistochemistry confirms the B-cell
nature of the neoplasm (CD20+). The final diagnosis was non-Hodgkin B-cell high
grade centroblastic lymphoma (KIEL classification). Postoperative studies failed
to show lymph node or bone marrow infiltration by neoplastic cells. We found
reports on only 60 malignant lymphomas, considered to be primary to the kidney.
They usually affect middle-aged people, can be diagnosed with imaging techniques,
and seem to show a better prognosis than other types of lymphoma.
PMID- 9653915
TI - Sarcomatoid carcinoma (carcinosarcoma) of the gallbladder.
AB - We report a case of carcinoma of the gallbladder in a 67-year-old woman. The
description comprises the histological, immunohistochemical, ultrastructural and
cytogenetical picture of the tumor. The ultrastructural features as well as
chromosomal changes may denote the epithelial derivation of the tumor studied.
PMID- 9653916
TI - Concurrence of localized Castleman's disease and peripheral small B-Lymphocytic
lymphoma within the same lymph node.
AB - Castleman's disease, also known as benign giant lymph node hyperplasia, is a
lymphoproliferative disorder which can occur either in a localized or
multicentric form. The latter is characterized by the development of malignant
lymphoma, Kaposi's sarcoma or carcinoma in 32% of cases. By contrast, localized
Castleman's disease has exceptionally been reported in association with non
Hodgkin's lymphoma and - to the best of our knowledge - never at the same
anatomic site. Here we describe the occurrence in the same lymph node of
localized Castleman's disease (with monotypic plasma cell component) and an
apparently unrelated peripheral small B-lymphocytic lymphoma.
PMID- 9653917
TI - Spindle cell hemangioendotheliomas associated with multiple skeletal
enchondromas: a variant of Maffucci's syndrome.
AB - An unusual case of Maffucci's syndrome confined to an extremity with an
additional superficial lymphangioma in the same limb is described. The patient, a
47-year-old woman, presented with several painful subcutaneous spindle cell
hemangioendotheliomas (SCHs) and multiple lytic bone lesions, some calcified, in
the left leg. She has been followed for two years and continues to do well. The
combination of SCHs and multiple enchondromas (ENCHs) should be searched in any
patient who presents with SCHs or multiple ENCHs, because there is a significant
risk of malignant transformation.
PMID- 9653918
TI - Solitary neurofibroma of the gallbladder. A case report and review of the
literature.
AB - Benign non-epithelial neoplasms of the gallbladder are rare. A case of incidental
neurofibroma of the gallbladder in a 44-year-old man without neurofibromatosis 1
is reported. The intramural tumor, located in the neck of the gallbladder, was
associated with lithiasis, chronic cholecystitis and localized fundic
adenomyomatosis. Seven cases including the present one are reviewed. The seven
patients ranged in age from 44 to 77 years, with an average age of 61.6 years.
Four of the seven patients were women. Five tumors appeared as mural nodules, and
two showed intraluminal growth. The most common location was the body of the
gallbladder. The size of the lesion varied from 0.3 to 5.3 cm, with a mean size
of 1.3 cm. Five of the seven cases were incidentally found in a gallbladder
resected for cholelithiasis. Using ultrasonography, two cases with no lithiasis
were detected preoperatively, presenting as intracavitary growing lesions by
ultrasonography. It is possible that neurofibroma of the gallbladder may be more
common than the small number of known cases indicates.
PMID- 9653919
TI - Osseous manifestation of Rosai-Dorfman disease (sinus histiocytosis with massive
lymphadenopathy). A case report and review of the literature.
AB - Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is an
unusual form of histiocytic disorder. Bone lesions are infrequent. We describe a
33-year-old man with involvement of multiple bones but without lymphadenopathy at
the time of presentation. The literature on osseous manifestation in this
condition is reviewed.
PMID- 9653920
TI - Gradient high-performance liquid chromatographic analysis of enkephalin peptides,
their metabolites, and enzyme inhibitors using combined ultraviolet and
electrochemical detection II. Application to ocular permeability studies in
vitro.
AB - A gradient HPLC method with combined ultraviolet (UV) and electrochemical
detection (ED) was used to study the ocular permeability of [D-Ala2]-methionine
enkephalinamide (MEA) in vitro. Coulometric ED was selective for MEA and its
tyrosine-containing metabolites with quantitation limits between 20 and 60 nM
(1.0-3.0 pmol per 50-microl injection), whereas UV detection at 205 nm allowed
the determination of several aromatic metabolites and enzyme inhibitors with
quantitation limits between 40 and 500 nM (2.0-25.0 pmol). This method was
capable of detecting permeability of MEA and metabolite formation in the cornea
and conjunctiva in vitro. Furthermore, effects of aminopeptidase inhibitor
bestatin and enkephalinase inhibitor SCH 39370 on permeation and metabolism of
MEA could be determined.
PMID- 9653921
TI - Determination of melatonin in rat pineal, plasma and retina by high-performance
liquid chromatography with electrochemical detection.
AB - A sensitive method for the routine measurement of endogenous melatonin (MEL) in
pineal, retina and plasma rat tissues has been developed using reversed-phase
high-performance liquid chromatography with electrochemical detection.
Quantification limit for MEL was 0.2 ng/mg protein in pineal, 15 pg/ml in plasma
and 2.0 pg/mg protein in retina. To improve both MEL quantification and the
reproducibility of the assay, an internal standard was used when an extraction in
organic solvent was required, in contrast with other available chromatographic
methods. MEL values and the circadian profile obtained in this study from both
rat pineal and plasma agree with those reported previously. This method allows
MEL detection in mammal retina, particularly in rat, where MEL levels are very
low.
PMID- 9653922
TI - Chromatographic separation of fluorescent thiol adducts of 4-chloro-7
sulphobenzofurazan. Use as substrates for enzymes of the mercapturic acid
xenobiotic pathway.
AB - Fluorescent adducts of 4-chloro-7-sulphobenzofurazan with cysteine,
cysteinylglycine, reduced glutathione and N-acetylcysteine were prepared. Adducts
were separated by HPLC on a 3-mm Nova-Pak C18 reversed-phase column using
isocratic elution with a solvent of acetonitrile-0.15 M phosphoric acid (5:95)
buffered at pH 2.5. The adducts were detected using a fluorescence detector set
at an excitation wavelength of 365 nm and an emission wavelength of 510 nm and an
ultraviolet detector at 254 nm. The adduct of reduced glutathione was also formed
by the action of the enzyme glutathione-S-transferase. This adduct acted as a
substrate for the enzyme gamma-glutamyltranspeptidase and the product of this
reaction, the 4-chloro-7-sulphobenzofurazanyl derivative of cysteinylglycine,
acted as a substrate for either dipeptidase or aminopeptidase M. The sequential
enzymic effects could be detected by changes in the relative fluorescence
intensity of the solutions to which the respective enzymes had been added but
were more appropriately followed by changes in the HPLC elution profiles after
enzymic treatment of solutions.
PMID- 9653923
TI - Analysis of urinary caffeine metabolites to assess biotransformation enzyme
activities by reversed-phase high-performance liquid chromatography.
AB - An isocratic high-performance liquid chromatography procedure was developed for
the analysis of five urinary metabolites of caffeine; caffeine or 1,3,7
trimethylxanthine (137X), paraxanthine or 1,7-dimethylxanthine (17X), 1,7
dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U) and 5-acetylamino
6-formylamino-3-methyluracil (AFMU). A standardized procedure was used for oral
intake of caffeine and for urine collection. Conditions for sample storage and
preparation were optimized, resulting in no detectable loss of caffeine
metabolites after storage of the urine samples for four months. Urine samples
were extracted with chloroform-2-propanol (4:1, v/v) and separated on a reversed
phase column with acetic acid (33%)-tetrahydrofuran-acetonitrile-water
(1:2.5:44:925.5, v/v) as the eluent. Peaks were monitored at 280 nm. Peak heights
were measured and the five metabolites were quantified using calibration curves.
Cytochrome P4501A2 (CYP1A2) activity was calculated from the molar ratio
(AFMU+1X+1U)/17U, N-acetyltransferase (NAT) from the ratio AFMU/1X, XO from the
ratio 1U/1X+1U and cytochrome P4502A6 (CYP2A6) from the ratio 17U/(17U+17X+1U+
1X+AFMU). The inter-assay coefficients of variation ranged from 1.7% for 17U to
5.7% for IX. The intra-individual variation in metabolite ratios determined in
two people, with intervals of a few days to several weeks between measurements,
ranged from 2. 1% for XO to 11.0% for CYP2A6. Using this procedure, metabolic
ratios were determined for four groups of subjects; healthy, non-smoking females
using oral contraceptives (OC users, n=5) and non-users (n=5), healthy nonsmoking
males (n=9) and children (n=7). Results found in this study were comparable to
results reported in the literature for subjects with similar characteristics. A
significantly higher CYP1A2 ratio was found for males (4.87+/-0.47) compared to
females (3.62+/-0.91: p=0.005, Mann-Whitney). For the other enzyme activities, no
significant differences were found between the groups of subjects in this study.
PMID- 9653924
TI - Simple microbore high-performance liquid chromatographic method for the
determination of dopamine and cocaine from a single in vivo brain microdialysis
sample.
AB - A microbore chromatographic method for the analysis of both dopamine and cocaine
from in vivo brain microdialysis samples is described. To eliminate the need for
separate chromatographic systems for each analyte, post-column electrochemical
and ultraviolet detection systems were arranged in series. The limit of
quantitation for dopamine (5 fmol) was well within range for detecting dialysate
concentrations of this neurotransmitter in rats which were in a baseline, drug
free state. The limit of quantitation for cocaine (0.5 pmol) was sufficient to
detect brain cocaine levels following the peripheral administration of a low dose
of this psychostimulant (5 mg/kg, i.p.). Estimates of dialysate dopamine and
cocaine concentrations after 5, 10 and 20 mg/kg cocaine (i.p.) were in agreement
with reports which utilized separate HPLC analyses for each analyte.
PMID- 9653925
TI - Quantification of busulfan in plasma by gas chromatography-mass spectrometry
following derivatization with tetrafluorothiophenol.
AB - A specific and highly sensitive method has been developed for the determination
of busulfan in plasma by gas chromatography-mass spectrometry using a deuterium
labeled busulfan (busulfan-d8) as internal standard. Plasma containing busulfan
and busulfan-d8 were extracted with ethyl acetate and derivatized with 2,3,5,6
tetrafluorothiophenol prior to the monitoring of specific ions. The limit of
quantification of the assay was 20 ng/ml and the calibration curve was linear
over the range of 10 to 2000 ng/ml of derivatized busulfan. This method was in
good agreement with the GC-MS assay using derivatization with sodium iodide and
measuring diiodobutane. In addition, a pharmacokinetic study of busulfan was
conducted in six children. The apparent oral clearance was 5.7+/-1.9 ml/kg/min
and the volume of distribution was 1.0+/-0.4 l/kg and were similar to those
previously reported in pediatric patients.
PMID- 9653926
TI - Determination of ropivacaine and [2H3]ropivacaine in biological samples by gas
chromatography with nitrogen-phosphorus detection or mass spectrometry.
AB - Bioanalytical methods for determining the total concentration of the new local
anaesthetic drug ropivacaine in blood plasma, urine and tissues are presented.
Ropivacaine is a drug mainly used in connection with surgery and for post
operative pain relief. The biological samples were prepared using liquid-liquid
extraction and analysed using capillary gas chromatography with nitrogen
phosphorus detection or mass spectrometry. The methods are highly selective and
reliable with a between-day precision, given as the relative standard deviation,
generally below 6%. More than 20000 samples have been analysed using the methods
described.
PMID- 9653927
TI - Gas chromatographic-mass spectrometric quantitation of dextropropoxyphene and
norpropoxyphene in hair and whole blood after automated on-line solid-phase
extraction. Application in twelve fatalities.
AB - After conversion of norpropoxyphene (NP) to its corresponding amide,
dextropropoxyphene (DP) and NP are extracted from 1 ml of blood or 50 mg of
powdered hair, on C18 cartridges and eluted using methanol containing 0.5% acetic
acid. Automated extraction is conducted on-line with automated device, starting
from buffered and centrifuged sample. After extraction, the dried residue is
reconstituted with 40 microl of methanol, and then injected in a gas
chromatograph at 250 degrees C. Quantitation is carried out by gas chromatography
mass spectrometry in the selected-ion monitoring mode, lidocaine being the
internal standard. The method gave relative standard deviations lower than 6.2%
in whole blood, and 6.0% in hair for the entire range of calibration from 0.5 to
10 microg/ml in blood and from 1 to 20 ng/mg in hair of both compounds. Limits of
detection in blood and hair for DP are, respectively, 0.07 microg/ml and 0.05
ng/mg, whereas the respective limits of detection in whole blood and hair for NP
are 0.09 microg/ml and 0.04 ng/mg. The present method was used for one year in
our laboratory. Postmortem concentrations of DP in blood ranged from 1.6 to 44.0
microg/ml (mean=9.8microg/ml, n = 12) and are comparable to those found in the
literature. Out of 30 hair samples from people who died from heroin overdose, 13
were positive both for DP and NP with concentrations ranging from 0.2 to 27.4
ng/mg (mean 8.7 ng/mg) for DP and 0.3 to 68.9 ng/mg (mean 24.1 ng/mg) for NP.
PMID- 9653928
TI - Gas chromatographic-tandem mass spectrometric determination of acetylsalicylic
acid in human plasma after oral administration of low-dose aspirin and guaimesal.
AB - A fully validated gas chromatographic-tandem mass spectrometric (GC-MS-MS) method
is described for the accurate determination of acetylsalicylic acid (ASA) in
human plasma after a single low-dose oral administration of aspirin or guaimesal,
an ASA releasing prodrug. ASA and the newly prepared O-[2H3]-acetylsalicylic acid
(d3-ASA) used as internal standard were determined in 100-microl aliquots of
plasma by extractive pentafluorobenzyl (PFB) esterification using PFB bromide and
tetrabutylammoniumhydrogen sulphate as the esterifying and ion-pairing agent,
respectively, and by GC-MS-MS analysis in the negative-ion chemical ionization
mode. The overall relative standard deviations were below 8% for ASA levels in
the range 0-1 microg/ml plasma. Mean accuracy was 3.8% for ASA levels within the
range 0-100 ng/ml. The limit of quantitation of the method was determined as 200
pg/ml ASA at an accuracy of 5.5% and a precision of 15.2%. The limit of detection
was determined as 546 amol of ASA at a signal-to-noise ratio of 10:1.
PMID- 9653929
TI - High-performance liquid chromatographic determination of drugs and metabolites in
human serum and urine using direct injection and a unique molecular sieve.
AB - Silicalite is a molecular sieve that contains an intricate system of channels
approximately 6 A in diameter. These channels are hydrophobic and have been shown
to retain relatively small hydrophobic and hydrophilic molecules from aqueous and
biological samples. Silicalite is shown to be a restricted-access medium that
permits the injection of biological fluids directly onto a HPLC column packed
with Silicalite, eliminating the need for sample preparation. The sample
macromolecules elute with high recovery mostly at the extraparticulate void.
Simultaneously, Silicalite allows various drugs and metabolites to enter the
channels and be retained. Recoveries >90% were generally obtained for a wide
variety of drugs and their metabolites from human serum and urine.
PMID- 9653930
TI - Determination of quinolone antibiotics in growth media by reversed-phase high
performance liquid chromatography.
AB - A simple, accurate, precise, and versatile high-performance liquid
chromatographic (HPLC) method was developed and validated for the determination
of three quinolone antibodies in Mueller-Hinton broth. The fluoroquinolone agents
studied were ciprofloxacin, ofloxacin, and sparfloxacin; other quinolone agents
have been identified using this method but not validated in this matrix
(levofloxacin, clinafloxacin, temafloxacin, and trovafloxacin). In addition,
several other biological growth mediums have been investigated (human serum,
human urine, Todd-Hewitt growth media, Ensure enteral feeding solution, and
Haemophilus growth media). This method uses UV detection (280 nm), a simple, one
step protein precipitation extraction, and separation using a C18 column with an
isocratic, ion-pairing mobile phase. An appropriate internal standard was
obtained by using another quinolone antibiotic of differing retention time. The
calibration curves were linear (r2> or =0.999) over a concentration range of
0.0625-20.0 microg/ml with a lower limit of quantification of 0.1 microg/ml. The
intra-day and inter-day coefficients of variation were less than 15%.
PMID- 9653931
TI - Stereoselective determination of R,S-2-[4-(3-methyl-2-thienyl)phenyl]propionic
acid and its taurine conjugates in dog urine by high-performance liquid
chromatography.
AB - Two high-performance liquid chromatographic methods for the stereoselective
determination of R,S-2-[4-(3-methyl-2-thienyl)-phenyl]propionic acid (R,S-MTPPA),
a new anti-inflammatory agent, and its taurine conjugates (R,S-MTPPA-TAU) in dog
urine have been developed and validated. The urine samples were subjected to
solid extraction or TLC preparation, then R,S-MTPPA and R,S-MTPPA-TAU were
separated on Chiralcel OD and Chiral AGP columns, respectively, with ultraviolet
absorbance detection at 272 nm. The dose-response relationships for enantiomers
of R,S-MTPPA and R,S-MTPPA-TAU were linear in the concentration ranges of 0.5-50
(r>0.9993) and 5-200 microg/ml (r>0.9982), respectively. Recoveries of all tested
enantiomers from dog urine were roughly 90% within the above concentration
ranges. Intra- and inter-day reproducibilities were sufficient for metabolic
studies. These methods were applied to stereoselective determination of the
enantiomers in dog urine after administration of either S- or R-MTPPA.
PMID- 9653932
TI - High-performance liquid chromatographic assay for the novel antitumor drug,
bryostatin-1, incorporating a serum extraction technique.
AB - An HPLC assay incorporating a solid-phase extraction technique has been devised
for bryostatin-1. Quantitation of bryostatin was found to be linear over the
concentration range 0.012-25 microg/ml (0.2-25 ng on column) and was found to
have a limit of detection of 0.2 ng on column, with a correlation coefficient of
0.9999. Following extraction of bryostatin over a range of concentrations from
horse serum (0.012-25 microg/ml) and human serum (0.01-0.32 microg/ml) using a
100-mg C18 solid-phase extraction cartridge, extraction efficiencies consistently
greater than 90% were obtained for extraction from horse serum and varied between
57 and 85% from human serum. However, on extending this work to blood samples
from patients undergoing therapy with bryostatin-1, the drug was not detectable
even at the maximum dose given, demonstrating the rapid loss of this agent from
peripheral circulation.
PMID- 9653933
TI - New isocratic high-performance liquid chromatographic procedure to assay the anti
sickling compound hydroxyurea in plasma with ultraviolet detection.
AB - A new procedure using high-performance liquid chromatography (HPLC) with
ultraviolet detection to assay hydroxyurea (HU) levels in plasma has been
developed. The drug was isolated from plasma by a direct deproteinization process
with sulfosalicylic acid. Following neutralization of the acidic supernatant, an
aliquot was loaded onto an Aminex HPX-72S column (300x7.8 mm). Chromatography was
performed at 55 degrees C using a mobile phase consisting of acetonitrile-0.025 M
ammonium sulfate buffer (pH 8.5) including 0.1% triethylamine, 0.01 M sodium
sulfate, and 5 mM sodium heptane sulfonate. The UV absorbance of effluent was
monitored at 214 nm. A flow-rate of 0.8 ml/min was used for analyzing HU in both
human and mouse plasma. Under these conditions, the drug eluted at 12.6 min. The
assay possessed linearity up to 425 microg/ml, with a lower limit of quantitation
of 3.32+/-0.0004 microg/ml (mean+/-S.D., n=10). Intra-day and inter-day
coefficients of variation were less than 8.5% and 8.7% respectively. Absolute
differences were less than 7.4%. The method has been employed in clinical studies
and the sensitivity of the assay was shown to be adequate for characterizing the
plasma pharmacokinetics of HU in mice. In conclusion, the procedure described
herein could be ideally suited for therapeutic monitoring of hydroxyurea.
PMID- 9653934
TI - Determination of minalrestat (an aldose reductase inhibitor) in rat, dog and
human plasma by high-performance liquid chromatography.
AB - A high-performance liquid chromatographic (HPLC) method was developed for the
quantification of minalrestat (a potent aldose reductase inhibitor) in rat, dog
and human plasma. Minalrestat and internal standard (I.S.) were extracted from
plasma by either solid-phase extraction (SPE) or liquid-liquid extraction (human
plasma). Plasma extracts were chromatographed on a Hypersil ODS column with 3
microm packing with a mobile phase of acetonitrile-0.05 M potassium phosphate
buffer, pH 3.0 (45:55, v/v) at 0.2 ml/min. The signal in the eluent was enhanced
by UV-irradiation when passing through a photochemical reaction unit with a 10-m
reaction coil, prior to detection by UV absorbance at 255 nm. The intra-day
coefficients of variation was less than 9% in rat, dog and human plasma and the
intra-day accuracy (%MRE) was within +/-5% in all matrices tested. The inter-day
coefficients of variation were less than 12% in rat and human plasma and the
accuracy (%MRE) was within +/-15%. Minalrestat was stable for at least 60 days in
rat and human plasma and at least 30 days in dog plasma samples stored at -20
degrees C. In human plasma samples, the analyte was stable for up to 5 cycles of
freezing and thawing. This method has been applied successfully for the
evaluation of the pharmacokinetics of minalrestat in rats, dogs and humans.
PMID- 9653935
TI - Determination of trichlormethiazide in bovine milk by high-performance liquid
chromatography.
AB - A liquid chromatographic procedure was developed and validated for the
quantitative determination of trichlormethiazide (TCMTZ) in bovine milk. Whole
milk was defatted by initial centrifugation at 4 degrees C. The resulting skim
milk was treated with lead acetate and acetonitrile, vortex mixed, and
centrifuged. The acetonitrile from the supernatant was back extracted in ethyl
acetate. The organic solvent mixture which contained TCMTZ was further treated
with sodium tungstate, vortex mixed, and centrifuged. The top organic layer was
removed and evaporated to dryness; the resulting residue was reconstituted in the
mobile phase, and the final extract was analyzed by high-performance liquid
chromatography (HPLC). The HPLC conditions employed included a polymer column, a
mobile phase consisting of 30% acetonitrile or 30% acetonitrile-tetrahydrofuran
(2:1, v/v) in a phosphate buffer (pH 3), and a UV detection at 225 nm. The
average recoveries of TCMTZ from milk fortified at 7, 14, 35, 70, and 140 ppb
were 88, 93, 117, 110, and 99%, respectively, with corresponding C.V. values of
7, 18, 11, 9, and 21%. The method was validated by assaying milk obtained from a
cow dosed with Naquasone. TCMTZ concentration was detected only in the 8 h post
dose milk samples and was determined to be 6 ppb.
PMID- 9653936
TI - Application of matrix-assisted laser desorption ionization time-of-flight mass
spectrometry to the analysis of glycopeptide-containing multiple O-linked
oligosaccharides.
AB - In our previous report [Iwase et al., J. Biochem., 120 (1996) 393], the number of
O-linked oligosaccharide chains on the hinge region of IgA1 was estimated by
matrix-assisted laser desorption ionization time-of-flight mass spectrometry
(MALDI-TOFMS). In this experiment, the number of non-substituted N
acetylgalactosamines and Galbeta1,3GalNAc residues, as the core O-linked
oligosaccharide structure per heavy chain of normal human serum IgA1, was
estimated by digestion of the asialo-hinge glycopeptide with alpha-N
acetylgalactosaminidase (GalNAc-ase) or endo-alpha-N-acetylgalactosaminidase
(endo-GalNAc-ase). GalNAc-ase treatment of the asialoglycopeptide produced two
major peaks, one being a glycopeptide containing four GalNAc and four Gal
residues, and the other contained three GalNAc and three Gal residues. Treatment
with endo-GalNAc-ase also produced a nearly equal amount of the two peaks, with
the naked hinge peptide and the peptide having one GalNAc residue. From those
results, we concluded that the asialo-hinge glycopeptide was composed of three
components bearing four Galbeta1,3GalNAc and one GalNAc, only four
Galbeta1,3GalNAc, and three Galbeta1,3GalNAc and one GalNAc, respectively. This
method was useful for determining the glycoforms on the IgA1 molecule with
respect to the core O-linked oligosaccharide structure.
PMID- 9653937
TI - Quantification of carbamylated dehydroascorbate derivative produced from cyanate
and dehydroascorbate.
AB - We established a high-performance liquid chromatographic method for separating
and quantifying carbamylated dehydroascorbate derivative (CDA), a reaction
product of cyanate with dehydroascorbate. The separation of CDA from interfering
substances was achieved by anion-exchange HPLC using a TSK gel SAX (250x4.6 mm
I.D.) column and 0.12 M NaCl eluent. The detection of CDA was achieved through
two steps: (1) degradation of CDA to cyanate and amino compounds in alkaline
solution, and (2) detection of these products by an indophenol reaction. For the
processing of plasma and urine samples, anion-exchange solid-phase extraction was
used. The detection limit for quantitative determination was 0.1 microM CDA
(S/N=3). The linear range found applying the optimized conditions was 0.2 to 200
microM. The intra- and inter-day assay precision (R.S.D.) of CDA (10 microM) were
4.8 and 7.2% for rat plasma, and 4.0 and 4.9% for rat urine, respectively. The
usefulness of the present method was proved by the application to plasma and
urine samples. The study of the biokinetics of CDA in rats revealed that the
elimination of CDA is due to urinary excretion.
PMID- 9653938
TI - Direct pharmaceutical analysis of bisphosphonates by capillary electrophoresis.
AB - Bisphosphonate compounds have been studied as a class of potential drugs for the
treatment of various bone diseases. However, the analyses of these compounds are
problematic because most of them do not contain strong chromophores. Based on the
unique structures of these compounds, we have employed a capillary
electrophoresis (CE) technique for the characterization of these compounds in
pharmaceutical dosage formulations. In this study, two CE methods were developed
for the determination of a bisphosphonate compound, 2-thioethane-1,1
bisphosphonic acid. The first method involved the use of an uncoated column, a
phosphate buffer, and hydrostatic injection with direct UV absorbance detection.
The method showed excellent resolution and precision with a reasonable detection
limit of 30 microg/ml. Sensitivity was further improved using a glycerol-coated
column, together with a phosphate buffer of higher concentration and
electrokinetic injection under sample stacking conditions. This modified method
revealed a significant improvement in sensitivity with a detection limit of about
50 ng/ml. Both methods demonstrated high simplicity and excellent reproducibility
and were successfully applied to the quantitative analyses of pharmaceutical
dosing solutions.
PMID- 9653939
TI - Influence of Cremophor EL on the quantification of paclitaxel in plasma using
high-performance liquid chromatography with solid-phase extraction as sample
pretreatment.
AB - For the quantitative determination of paclitaxel in human plasma reversed-phase
high-performance liquid chromatographic (HPLC) methods with solid-phase
extraction (SPE) as sample pretreatment procedure are frequently used. Recovery
problems arose during the quantification of paclitaxel in plasma samples of
patients. The major problems were a large batch-to-batch difference in
performance of the SPE columns and the effects of the pharmaceutical vehicle
Cremophor EL on the performance of the SPE. Cremophor EL concentrations exceeding
1.0% (v/v) had a great impact on the absolute recovery of paclitaxel from human
plasma with the SPE procedure. The recoveries decreased approximately 10 to 40%
depending on the quality of the batch SPE columns. The problems are avoided by
using 2'-methylpaclitaxel as the internal standard. This study points out the
importance of including the effects of a pharmaceutical vehicle, like Cremophor
EL, in the validation programme of a bioanalytical assay and the use of an
internal standard in HPLC paclitaxel assays preceded by SPE as sample
pretreatment procedure.
PMID- 9653940
TI - Ion chromatography method and validation for the determination of sulfate and
sulfamate ions in topiramate drug substance and finished product.
AB - A stability-indicating assay method has been developed for monitoring topiramate
degradation in drug substance and finished product by quantifying sulfamate and
sulfate ions. Topiramate in the solid state is stable under ambient conditions
but can degrade under stress conditions (elevated temperatures and humidities).
This method detects and quantitates sulfamate and sulfate ions (the inorganic
part of the decomposition) and in conjunction with an assay method for topiramate
and its known organic degradation product provides total molar accountability.
The chromatographic system consists of a sodium hydroxide gradient (2-25 mM) and
an anion-exchange HPLC column and an anion suppressor. The analysis is complete
in 30 min. The method utilizes the same sample preparation as the topiramate
assay method which increases sample efficiency and throughput. The method has
been validated for analysis of degraded and nondegraded topiramate drug substance
and finished product.
PMID- 9653941
TI - Modified cyclodextrins as chiral selectors: molecular modelling investigations on
the enantioselective binding properties of heptakis(2,3-di-O-methyl-6-O-tert.
butyldimethylsilyl)-beta-cyclodextri n.
AB - Molecular modelling methods have been used to investigate the enantioselective
binding properties of chiral dihydrofuranones on heptakis(2,3-di-O-methyl-6-O
tert.-butyldimethylsilyl)-beta-cyclod extrin in capillary gas chromatography. A
conformational analysis of the modified beta-cyclodextrin was performed using
annealed molecular dynamics. With the program GRID the molecular interaction
potential for each of the received energetically reasonable structures of the
beta-cyclodextrin and the dihydrofuranones was evaluated using different probe
groups. The results of these computations have been used as starting points for
constructing geometrically reasonable host-guest complexes between the beta
cyclodextrin and the dihydrofuranones. The subsequently performed molecular
dynamics simulations yielded different complex states reflecting the
conformational flexibility of the diastereomeric complexes. Considering the
evaluated interaction energy between the beta-cyclodextrin and the
dihydrofuranones as a measure of complex stability the results are in close
agreement with the experimentally determined elution sequences. The methodology
for the construction of the interaction model used in this study is capable of
simulating the experimental data. We believe that it may serve as a basis for
predictions of hitherto unknown elution sequences at modified cyclodextrins.
PMID- 9653942
TI - Rapid separation and quantitation of combined neutral and polar lipid classes by
high-performance liquid chromatography and evaporative light-scattering mass
detection.
AB - Modifications are described for an innovative and widely used high-performance
liquid chromatography technique that resolves a very broad spectrum of lipids for
quantitation by evaporative light-scattering detection. Substitution of acetone
for 2-propanol in a portion of the solvent gradient program yields consistent
resolution of diacylglycerol and cholesterol without sacrificing baseline
resolution of the remaining major lipid classes. Moreover, previously noted
instabilities in triacylglycerol retention time are eliminated. The introduction
of acetone also enables a 20% reduction in flow-rate without an increase in total
run time. As a further modification of the mobile phase composition, acetic acid
and ethanolamine are substituted for the serine-ethylamine combination that was
originally shown to improve column performance. The combination of acetic acid
and ethanolamine yields the same result but the increased volatility of these
solutes over serine results in decreased baseline noise. Finally, 1,2
hexadecanediol is introduced as an internal standard that is well suited for this
method. The chromatographic performance obtained with these modifications is
demonstrated in compositional analyses of lipid extracts from rat liver, heart,
kidney and brain.
PMID- 9653943
TI - Determination of glutamate and aspartate in microdialysis samples by reversed
phase column liquid chromatography with fluorescence and electrochemical
detection.
AB - Five different systems for fast determination of aspartate and glutamate in
microdialysis samples are described: (I) a high-speed HPLC using a gradient pump
with a sharp elution profile, (II) a column switching technique, (III) an
isocratic pump with a low-pressure switching valve for one-step gradients, (IV)
microbore chromatography using injections of acetonitrile as a wash-out step, (V)
on-line connection of microdialysis and HPLC/derivatization. In all cases,
automated precolumn derivatization with o-phthalaldehyde-2-mercaptoethanol
reagent were used. Both fluorescence and electrochemical detection techniques
were evaluated in terms of reproducibility, sensitivity, interference,
maintenance and troubleshooting. The electrochemical detection method required a
second derivatization step with 0.2 M iodoacetamide to remove excess of a thiol
moiety and regular recalibrations after each six to ten injections. Under these
conditions the correlation coefficients for electrochemical vs. fluorescence
detectors were 0.918 for Asp and 0.988 for Glu for 65 microdialysis samples.
Coefficients of variation for six analyses between calibrations were below 3% for
both detectors. The limits of detection for both amino acids were about 0.4 pmol
for electrochemical detection with a thiol scavenger step, 50 fmol for
fluorescence detection using conventional columns and about 20-30 fmol for the
microbore system. All systems are suitable for detecting basal levels of Asp and
Glu in 5-10 microl microdialysis samples from a rat brain where typical
concentrations lie around 1-10 pmol or more. It is concluded that a microbore
setup with one isocratic pump and an autosampler optimized for injections of
washing solvent between samples is the most practical and economical. The system
allows analysis of minute sample volumes down to 1-2 microl.
PMID- 9653944
TI - Highly sensitive measurement of lipid molecular species from biological samples
by fluorimetric detection coupled to high-performance liquid chromatography.
AB - As the molecular species composition of glycerophospholipids provides more
valuable information than the corresponding fatty acid composition, we have
applied a fluorimetric detection (360 and 460 nm for excitation and emission
wavelengths, respectively) of anthroyl derivatives of diradylglycerol species to
minor phospholipid classes and subclasses from biological samples. Diacylglycerol
species were obtained by phospholipase C treatment of phosphatidylcholine
subclasses and phosphatidic acid extracted from rat thymocytes. Subpicomole
measurements of molecular species from the minor subclass
alkenylacylglycerophosphocholine could be achieved (e.g. 0.4 pmol of the
18:1/20:5 species). Such a sensitivity allowed study of the molecular species
composition of another minor phospholipid, phosphatidic acid, and to evaluation
of its alteration in mitogen-stimulated thymocytes as compared to unstimulated
ones. Finally, we report that such a measurement is also applicable to other
minor bioactive lipids with a hydroxyl group available, namely
hydroxyeicosatetraenoates (HETEs), with a similar gain of sensitivity over
conventional UV detection. Overall, these measurements, especially those of
phospholipid molecular species, are sensitive, reliable and meaningful for
precursor-product relationship between phospholipids.
PMID- 9653945
TI - Determination of gamma-aminobutyric acid in microdialysis samples by microbore
column liquid chromatography and fluorescence detection.
AB - A method for the determination of gamma-aminobutyric acid (GABA) at
concentrations as low as 1.5 nM in microdialysis samples is described. A high
performance liquid chromatography (HPLC) autosampler was used for precolumn
derivatizations of samples with phthalaldehyde-2-mercaptoethanol reagent, as well
as for automated injections of acetonitrile to wash the microbore column between
injections. This permitted the use of only one isocratic pump and reduced the run
to-run analysis time to below 20 min, without any risk for late-eluting peaks.
Three different microbore columns were evaluated. The optimal column was a 150 x
1 mm I.D., C18 reversed-phase silica column with a particle size of 3 microm,
operated at a flow-rate of 50 microl/min. The mobile phase was 0.1 M sodium
acetate buffer, pH 5.4, containing 20% acetonitrile. Under these conditions, the
column exhibits a low back-pressure of about 11.1 MPa and is usable for at least
1000 injections. Good correlation was found between fluorescence and
electrochemical detector responses for o-phthaldialdehyde-GABA derivatives,
although the latter detector type generally required more skill and maintenance
for routine use. Microdialysis samples of 10-20 microl, recovered from various
rat brain nuclei, were assayed using the described method.
PMID- 9653946
TI - Analysis of cysteine and N-acetylcysteine in human plasma by high-performance
liquid chromatography at the basal state and after oral administration of N
acetylcysteine.
AB - A high-performance liquid chromatographic method for the determination of free
reduced cysteine and N-acetylcysteine in human plasma at the basal state and
after oral administration of N-acetylcysteine is described. The method is based
on acid-catalysed conversion of plasma thiols to the corresponding S-nitroso
derivatives by excess of nitrite and their subsequent cation-pairing RP-HPLC with
detection at 333 nm. Recovery rates of cysteine and N-acetylcysteine added to
human plasma were 94.6 and 99.6%, respectively. Inter- and intra-day precision
were below 6%. In healthy humans (n = 5), free reduced cysteine was determined to
be (mean+/-S.E.) 10.0+/-0.96 microM. No N-acetylcysteine was detected in plasma
of these subjects above the limit of detection (e.g. 170 nM). The method was
successfully applied to a pharmacokinetic study on orally administered N
acetylcysteine to healthy volunteers.
PMID- 9653947
TI - Sensitive method for the quantification of beta-glucuronidase activity in human
urine using capillary electrophoresis with fluorescence detection.
AB - Capillary electrophoresis (CE) with fluorescence detection was used to determine
the concentration of 4-methylumbelliferone liberated from 4-methylumbelliferyl
beta-D-glucuronide by beta-glucuronidase. Enzyme substrate saturation kinetics
were studied in buffer and the pH range for the enzyme reaction was optimized. A
linear relationship of initial enzyme reaction velocity as a function of peak
area of enzyme product was obtained for enzyme activity ranging from 1 to 100
units. The beta-glucuronidase activity in urine was next determined. Freshly
collected urine samples were dialyzed, the retentate was incubated with 4
methylumbelliferyl-beta-D-glucuronide, boiled and centrifuged. The supernatant
was separated by CE in an uncoated capillary with 0.1 M sodium acetate buffer by
applying a voltage of 12 kV. The product of the enzymatic reaction, 4
methylumbelliferone, was detected by fluorescence, facilitating the determination
of as little as one unit of beta-glucuronidase activity in a 0.5-h incubation
time, with an error of less than +/-5%.
PMID- 9653948
TI - Determination of lycopene, alpha-carotene and beta-carotene in serum by liquid
chromatography-atmospheric pressure chemical ionization mass spectrometry with
selected-ion monitoring.
AB - A selected-ion monitoring (SIM) determination of serum lycopene, alpha-carotene
and beta-carotene by an atmospheric pressure chemical ionization mass
spectrometry (APCI-MS) was developed. A large amount of serum cholesterols
disturbed the SIM determination of carotenoids by contaminating the segment of
interface with the LC-MS. Therefore, separation of carotenoids from the
cholesterols was performed using a mixed solution of methanol and acetonitrile
(70:30) as the mobile phase on a C18 column of mightsil ODS-5 (75 mm x 4.6 mm
I.D.). The SIM determination was carried out by introducing only the peak
portions of carotenoids and I.S. (squalene) by means of an auto switching valve.
In the positive mode of APCI-MS, lycopene, alpha-carotene and beta-carotene were
monitored at m/z 537 and I.S. was monitored at m/z 411. This method was linear
for all analytes in the range of 15-150 ng for lycopene, 7-70 ng for alpha
carotene and 25-50 ng for beta-carotene. The detection limit of LC-APCI-MS-SIM
for carotenoids was about 3 ng per 1 ml of serum (S/N = 3). The repeatabilities,
expressed as C.V.s, were 10%, 8.4% and 5.3% for lycopene, alpha-carotene and beta
carotene, respectively. The intermediate precisions, expressed as C.V.s, were
11.2%, 8.8% and 6.5% for lycopene, alpha-carotene and beta-carotene,
respectively.
PMID- 9653949
TI - Subnanomolar quantification of caffeine's in vitro metabolites by stable isotope
dilution gas chromatography-mass spectrometry.
AB - A method for the quantification of subnanomolar levels of in vitro metabolites of
caffeine by an isotope dilution gas chromatographic-mass spectrometric (GC-MS)
assay has been developed and applied. Trideuteromethylated analogs of each
primary metabolite were synthesized and added after incubations of caffeine with
human liver microsomes high in cytochrome P4501A2. HPLC separation of the
metabolites prior to GC-MS quantification allowed the isolation of theobromine
and paraxanthine which coeluted by GC and enabled quantification over a larger
dynamic range. Quantitative analysis was performed on the n-propylated
derivatives by selected-ion monitoring of either the M+. ions for the
dimethylxanthines or [M-C3H6]+. ions for 1,3,7-trimethyluric acid. For the least
abundant metabolite (1,3,7-trimethyluric acid), the detection level on column was
200 pg. Replicate analyses exhibited intra- and inter-day variability of 4.2 and
7.9%, respectively. This assay has been successfully used in the quantification
of caffeine's primary metabolites in more than 180 incubations, at varying
substrate concentrations and with multiple enzyme sources.
PMID- 9653950
TI - Rapid method for the simultaneous measurement of nicotine and cotinine in urine
and serum by gas chromatography-mass spectrometry.
AB - A simple, sensitive, and rapid gas chromatographic-mass spectrometric method is
described for the simultaneous detection and quantitation of nicotine and its
metabolite, cotinine, in urine and serum. The analytes and their respective
deuterated internal standards were extracted by liquid-liquid extraction coupled
to centrifugation and evaporation. The detection limit of the assay was 0.16
ng/ml for both nicotine and cotinine. The limit of quantitation for each analyte
was 1.25 ng/ml.
PMID- 9653951
TI - Rapid and sensitive high-performance liquid chromatographic determination of
nicotine and cotinine in nonsmoker human and rat urines.
AB - A simple reversed-phase high-performance liquid chromatographic method with
paired-ion and UV detection has been developed for the rapid quantification of
urinary nicotine and cotinine. A one-step solid-liquid extraction on Extrelut was
used. Separation from endogenous substances was achieved with a decreasing flow
rate. With 20 ml of urine for extraction, the limit of quantification was 0.5
ng/ml for cotinine and 5 ng/ml for nicotine; linearity was obtained from 50 to
5000 ng/ml. The intra- and inter-day coefficients of variation were less than 9%
for cotinine and 30% for nicotine. Average recoveries for cotinine were 92-100%
and 47-86% for nicotine. The present method was applied to the urine analysis of
smokers, nonsmoker children, and experimental animals.
PMID- 9653952
TI - Determination of pilocarpine, isopilocarpine, pilocarpic acid and isopilocarpic
acid in human plasma and urine by high-performance liquid chromatography with
tandem mass spectrometric detection.
AB - A method is described for the determination of pilocarpine and its degradation
products isopilocarpine, pilocarpic acid and isopilocarpic acid in human plasma
and urine. The method is based on a simple sample preparation step --
ultrafiltration for plasma and dilution for urine samples -- followed by a
reversed-phase liquid chromatographic separation of the analytes and detection by
means of tandem mass spectrometry. Parameters affecting the performance of these
steps are discussed. The high sensitivity and selectivity of the method allow low
ng/ml concentrations to be determined for all compounds in plasma and undiluted
urine, which enables the investigation of the metabolic fate and elimination of
pilocarpine after oral administration to humans.
PMID- 9653953
TI - Validated method for the determination of idazoxan in human plasma by liquid
chromatography with tandem mass spectrometric detection.
AB - A liquid chromatography-tandem mass spectrometry method for the determination of
idazoxan in human (heparin) plasma is presented, which was developed and
validated using 500 microl of sample. Sample preparation consisted of the
addition of fluoroidazoxan as the internal standard, extraction at alkaline
conditions into tert.-butyl methyl ether, followed by centrifugation, evaporation
of the solvent and reconstitution in methanol. After a short chromatographic run,
detection took place by ionspray tandem mass spectrometry in positive ion mode.
Validation results on linearity, specificity, accuracy, precision and stability,
as well as application of the method to samples from a clinical trial, are shown.
The validated calibration range is from 0.300 to 100 ng/ml, with accuracy (bias)
and precision (coefficient of variation) being below 15% at all levels. A sample
throughput of, typically, 150 per day can be achieved.
PMID- 9653954
TI - Quantitative liquid chromatographic-tandem mass spectrometric determination of
orlistat in plasma with a quadrupole ion trap.
AB - This report evaluates the use of a quadrupolar ion trap for quantitation in a
bioanalytical laboratory. The evaluation was accomplished with the cross
validation of an LC-MS-MS quantitative method previously validated on a triple
quadrupole mass spectrometer. The method was a multi-level determination of the
anti-obesity drug, orlistat, in human plasma. The method has been refined
previously on a triple quadrupole instrument to provide rapid sample throughput
with robust reproducibility at sub-nanogram detection limits. Optimization of the
method on the ion trap required improved chromatographic separation of orlistat
from interfering plasma matrix components coextracted during the initial liquid
liquid extraction of plasma samples. The ion trap produces full-scan collision
induced dissociation mass spectra containing characteristic orlistat fragment
ions that are useful for quantitation. Data collection on the ion trap required a
precursor ion isolation width of 3.0 Da and optimal quantitative results were
obtained when three fragment ions were monitored with a 1.8 Da window for each
ion. Although a direct cross-validation between the ion trap and the tandem
triple quadrupole mass spectrometer was not possible, quantitative results for
orlistat comparable to those obtained from the triple quadrupole instrument were
achieved by the ion trap with the modified method. The limit of quantitation for
orlistat in plasma on the ion trap was 0.3 ng ml(-1) with a linear dynamic range
of 0.3 to 10 ng ml(-1). Precision and accuracy varied from 4 to 15% over the
quantitation range. The overall results provide an example of the utility of an
ion trap in bioanalytical work.
PMID- 9653955
TI - How to better define the characteristics of dispersion of results in liquid
chromatographic analyses through an interlaboratory study. Example of
collaborative studies on ketoprofen and spiramycin.
AB - The aim of this study was to use statistical tools, especially the analysis of
variance (ANOVA), to improve knowledge of the characteristics of the dispersion
of results in high-performance liquid chromatography (HPLC) methods for
quantitative analysis. It is in this regard that two interlaboratory studies have
been carried out in collaboration with Rhone-Poulenc Rorer. The first concerned
the analysis of a single drug product (ketoprofen) and was typically a "simple
analysis". The second one involved a complex mixture of drug products and related
substances (spiramycin), requiring far more constraining analysis conditions.
Preliminary studies of the analyses were carried out to develop an optimized
protocol. Statistical exploitation of the data for ketoprofen showed that there
was no significant influence of the factors "laboratory" and "preparation", under
the conditions of the study. On the other hand, in the case of spiramycin, a
significant influence of the factors "laboratory" and "preparation" was observed
under the conditions of the collaborative study, indicating that the latter
factor must be taken into account to establish certified assays. Results of these
two studies will help to determine the factors that have a significant influence,
depending on the product and the chromatographic method used. By completing the
statistical data base, interlaboratory studies will also contribute in the near
future to the elaboration of more rigorous protocols for analytical transfers.
PMID- 9653956
TI - Liquid chromatographic separation of doxycycline and 4-epidoxycycline in a tissue
depletion study of doxycycline in turkeys.
AB - Liver and muscle tissue residues of doxycycline in turkeys were determined
following administration of 25 mg doxycycline x HCl/kg BW in the drinking water
under field conditions. Quantitation was performed using a validated HPLC method
with fluorescence detection. The method was able to separate doxycycline and its
4-epimer, 4-epidoxycycline. This epimer was found in both liver and muscle
tissue. The detection limits of the method were estimated at 1.2 ng/g and 1.0
ng/g of doxycycline in liver and muscle tissue, respectively, using a signal-to
noise ratio of 3:1. The recovery of doxycycline was determined from spiked
tissues and was 63+/-3.8% and 66+/-3.1% for liver and muscle, respectively (n =
6). Within-day and between-day imprecision, expressed as the R.S.D. was below
7.4%. Linear calibration curves (r>0.997) were obtained in spiked liver between 0
and 1500 ng/g and in spiked muscle between 0 and 500 ng/g. A good stability of
doxycycline was observed in liver samples after storage for 22 days at -20
degrees C. The correlation between the residues in the liver and the muscle was
expressed as the correlation coefficient r and was 0.9884. The depletion kinetics
of doxycycline fitted a one-compartment model. The elimination half-life (T1/2)
of doxycycline was 77.7 h and 78.0 h in muscle and liver, respectively.
Furthermore, the residue depletion kinetics were used to establish a withdrawal
period in conformity with official guidelines. The withdrawal times necessary to
reach concentrations below maximum residue limits (MRLs), as imposed by the EU,
were 12 days and 17 days for liver and muscle tissue, respectively.
PMID- 9653957
TI - Stability-indicating analysis of isoxazolyl penicillins using dual wavelength
high-performance liquid chromatography.
AB - Stability-indicating high-performance liquid chromatography analytical procedures
were developed for specific determination of four isoxazolyl penicillins during
degradation under neutral and accelerated acid/alkali conditions. The
chromatographic conditions were set so that the drug peak was well separated from
the peaks of the degradation products. Peak homogeneity of the resolving drug
peak was assessed by the shape of the ratio chromatogram. Good and reproducible
separations were achieved on a reversed-phase column using a mobile phase
consisting of acetonitrile and a solution of 20 mM potassium dihydrogen phosphate
plus 10 mM tetramethylammonium chloride in water (adjusted to pH 5). Optimal
separations for all four drugs were achieved within the range of 15-21% organic
modifier in the mobile phase. The detection wavelengths were 220 nm and 240 nm.
The stability-indicating nature of the methods was confirmed by the linearity of
the pseudo-first order plots. The utility of dual-wavelength chromatography in
establishment of stability-indicating assays is highlighted.
PMID- 9653958
TI - Simultaneous high-performance liquid chromatographic determination of
quinupristin, dalfopristin and their main metabolites in human plasma.
AB - Quinupristin-dalfopristin (30:70, w/w) is a new streptogramin, which has been
developed for intravenous use. A specific and sensitive HPLC method was developed
to measure simultaneously quinupristin (RP 57669) and dalfopristin (RP 54476) and
their main metabolites in human plasma. The metabolites measured by this method
were RP 69012 (glutathione-conjugated) and RPR 100391 (cysteine-conjugated) from
quinupristin and RP 12536 (natural pristinamycin IIA), from dalfopristin. Solid
phase extraction with disposable cartridges was combined with reversed-phase HPLC
and fluorimetric detection for RP 57669, RP 69012 and RPR 100391 and UV detection
for RP 54476 and RP 12536. The method provided good recovery and low limits of
quantitation (0.025 mg l(-1) for RP 57669, RP 54476 and RP 12536, and of 0.010 mg
l(-1) for RP 69012 and RPR 100391). The validated range of concentrations of the
method was: 0.025-5000 mg l(-1) for RP 57669, RP 54476 and RP 12536 and 0.010
0.750 mg l(-1) for RP 69012 and RPR 100391.
PMID- 9653959
TI - High-performance liquid chromatography analysis of Bobel-24 in biological samples
for pharmacokinetic, metabolic and tissue distribution studies.
AB - A rapid and simple HPLC method is described for the determination of Bobel-24
(2,4,6-triiodophenol) and other iodinated derivatives in biological samples. The
sample preparation was liquid-liquid extraction before injection onto the HPLC
system. 2,6-Diiodo-4-methylphenol was used as internal standard. Separation was
obtained using a reversed-phase column under isocratic conditions. The mobile
phase consisted of water-acetonitrile (62:38). 2,4,6-Triiodophenol was detected
at 277 nm. This method was used for Bobel-24 determination in plasma, urine,
synovial liquid and different tissues. The assay was applied to pharmacokinetic
studies in dog and horse plasma and different dog tissues for tissue distribution
profiles toxicological and metabolic studies. In addition, this method for
biological samples can be applied to non-biological samples such as
pharmaceutical formulations in stability studies and quality control assays.
PMID- 9653960
TI - Enantioselective analysis of propafenone in plasma using a polysaccharide-based
chiral stationary phase under reversed-phase conditions.
AB - We present a method for the enantioselective analysis of propafenone in human
plasma for application in clinical pharmacokinetic studies. Propafenone
enantiomers were resolved on a 10-microm Chiralcel OD-R column (250 x 4.6 mm
I.D.) after solid-phase extraction using disposable solid-phase extraction tubes
(RP-18). The mobile phase used for the resolution of propafenone enantiomers and
the internal standard propranolol was 0.25 M sodium perchlorate (pH 4.0)
acetonitrile (60:40, v/v), at a flow-rate of 0.7 ml/min. The method showed a mean
recovery of 99.9% for (S)-propafenone and 100.5% for (R)-propafenone, and the
coefficients of variation obtained in the precision and accuracy study were below
10%. The proposed method presented quantitation limits of 25 ng/ml and was linear
up to a concentration of 5000 ng/ml of each enantiomer.
PMID- 9653961
TI - Simultaneous determination of codeine and its seven metabolites in plasma and
urine by high-performance liquid chromatography with ultraviolet and
electrochemical detection.
AB - A sensitive and selective high-performance liquid chromatography method has been
developed for the measurement of codeine and its seven metabolites, norcodeine,
morphine, normorphine, codeine-6-glucuronide, morphine-6-glucuronide, morphine-3
glucuronide and norcodeine glucuronide, in plasma and urine. The compounds were
recovered from plasma and urine using solid-phase extraction with C18 cartridges
and separated on a reversed-phase C8 column with a mobile phase consisting of 77%
buffer (5 mM sodium phosphate monobasic and 0.70 mM sodium dodecyl sulfate, pH
2.35) and 23% acetonitrile. Codeine, norcodeine, codeine-6-glucuronide,
norcodeine glucuronide and morphine-3-glucuronide were detected by ultraviolet
detection at 214 nm, with a detection limit of 0.02 nmol/ml for each compound in
plasma. Morphine-6-glucuronide, normorphine and morphine were monitored by
electrochemical detection at 350 mV, with a detection limit of 0.003 nmol/ml for
each compound in plasma. The assay showed good reproducibility and accuracy using
external standardization. The recovery and inter-day variation for all compounds
in plasma samples were 63.40-77.90% and 3.49-16.77% (R.S.D.) and while in urine
were 64.98-90.13% and 2.93-9.96% (R.S.D.), respectively.
PMID- 9653962
TI - Determination of free concentration of sameridine in blood plasma by
ultrafiltration and coupled-column liquid chromatography.
AB - Sameridine is a new candidate drug with both local anaesthetic and analgesic
properties. The free concentration of sameridine in blood plasma was determined
by coupled-column liquid chromatography. Following adjustment of the pH and the
temperature of the plasma samples, the free fraction was prepared by
ultrafiltration. The coupled-column liquid chromatographic system consisted of a
reversed-phase column, a cation-exchange extraction column and a cation-exchange
analytical column. Sameridine was detected by UV determination at 205 nm and the
system showed high selectivity. The limit of quantification was 1 nM and the
within-day precision was 4.6% (R.S.D., n = 10).
PMID- 9653963
TI - Simple high-performance liquid chromatographic method with electrochemical
detection for the simultaneous determination of artesunate and dihydroartemisinin
in biological fluids.
AB - A simple, rapid, sensitive, selective and reproducible high-performance liquid
chromatographic method with reductive electrochemical detection is described for
the simultaneous quantification of artesunate (ARS) and dihydroartemisinin (DHA)
in plasma. The procedure involved the extraction of ARS, DHA and the internal
standard (artemisinin, ARN) with a mixture of dichloromethane and tert.-methyl
butyl ether (8:2, v/v). Chromatographic separation consisted of the mobile phase
(acetonitrile-water containing 0.1 M acetic acid, pH 4.8; 45:55, v/v) running
through the column (Nova-Pak C18, 150 cm x 3.9 mm I.D., 5 microm particle size).
The retention times of alpha-DHA, beta-DHA, ARS and ARN were 2.9, 4.2, 4.5 and
6.0 min, respectively. The average recoveries of ARS, alpha-DHA and ARN in the
concentration range of 10-800 ng/ml were 81.9, 88.2, 101.1 and 84.3%,
respectively. The coefficients of variation (precision and repeatability) were
below 10% for all three compounds at concentrations of 50, 200, 400 and 800
ng/ml, and below 20% at a concentration of 10 ng/ml. The limits of quantification
for both ARS and alpha-DHA in spiked plasma samples were 5 and 3 ng/ml,
respectively. The method was found to be suitable for application to
pharmacokinetic studies of both ARS and DHA.
PMID- 9653964
TI - High-performance liquid chromatographic method for the determination of the major
quinine metabolite, 3-hydroxyquinine, in plasma and urine.
AB - The determination of 3-hydroxyquinine in urine and plasma samples is described.
Extraction was performed using a mixture of toluene-butanol (75:25, v/v),
followed by back-extraction into the mobile phase, which consisted of 0.1 M
phosphate buffer, acetonitrile, tetrahydrofuran and triethylamine. A reversed
phase liquid chromatography system with fluorescence detection and a CT-sil C18
column were used. The within-assay coefficient of variation of the method was 2%
at the higher concentration values in plasma, 2.95 microM, 4% at 227 nM and 9% at
the lower limit of quantitation, 4.5 nM. In urine, the coefficient of variation
was 11% at the lower concentration, 227 nM and was 3% at 56.8 microM. The between
assay coefficient of variation was 4% at the low concentration (5.1 nM) in
plasma, 2% at 276.8 nM and 3% at 1.97 microM. In urine, the between assay
coefficient of variation was 4% at 204.6 nM, 3% at 5.12 microM and 2% at 56.8
microM.
PMID- 9653965
TI - Reversed-phase high-performance liquid chromatography of 4-(2-pyridyl)-1
piperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydrochloride
(NSC 348977), a synthetic thiosemicarbazone with antitumor activity.
AB - Reversed-phase HPLC conditions for the separation of 4-(2-pyridyl)-1
piperazinethiocarboxylic acid 2-[1-(pyridyl)-ethylidene]hydrazide dihydrochloride
(NSC 348977, I), a synthetic thiosemicarbazone with antitumor activity, from
mouse plasma have been investigated. Following denaturization and precipitation
of the spiked plasma with acetonitrile, an aliquot of the supernatant was diluted
with aqueous buffer and subjected to analysis on a Nova-Pak C18 column (150 x 3.9
mm I.D.) by isocratic elution with 50 mM aqueous potassium phosphate buffer (pH
6.8, containing 1 mM EDTA)-acetonitrile (60:40, v/v). The column effluent was
monitored for UV absorption at 310 nm. Problems identified in the sample
preparation and separation of I include sensitivity to oxygen, light, non-neutral
pH and the presence of metal ions. These factors were seen to adversely influence
sample recovery, and attempts were made to find conditions which minimize their
effects.
PMID- 9653966
TI - Development of a highly sensitive high-performance liquid chromatographic method
for measuring an anticancer drug, UCN-01, in human plasma or urine.
AB - We have established a highly sensitive high-performance liquid chromatographic
method for the determination of an anticancer drug, UCN-01, in human plasma or
urine. Using a fluorescence detector set at an excitation wavelength of 310 nm
and emission monitored at 410 nm, there was a good linearity for UCN-01 in human
plasma (r=0.999) or urine (r=0.999) at concentrations ranging from 0.2 to 100
ng/ml or 1 to 400 ng/ml, respectively. For intra-day assay, in plasma samples,
the precision and accuracy were 1.8% to 5.6% and -10.0% to 5.2%, respectively.
For inter-day assay, the precision and accuracy were 2.0% to 18.2% and 2.4% to
10.0%, respectively. In urine samples, the intra- and inter-day precision and
accuracy were within 3.9% and +/-2.7%, respectively. The lower limit of
quantification (LLOQ) was set at 0.2 ng/ml in plasma and 1 ng/ml in urine. UCN-01
in plasma samples was stable up to two weeks at -80 degrees C and also up to four
weeks in urine samples. This method could be very useful for studying the human
pharmacokinetics of UCN-01.
PMID- 9653967
TI - High-performance liquid chromatography determination of mycophenolic acid and its
glucuronide metabolite in human plasma.
AB - Two HPLC-UV assays are reported here: one is a rapid assay for mycophenolic acid
(MPA) and the other is a simultaneous assay for MPA and its metabolite
mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500
microl) with added internal standard were acidified and extracted using C18 solid
phase extraction cartridges. Chromatographic separation was achieved on a C18
Novapak column using a mobile phase consisting of methanol-0.05% orthophosphoric
acid (40:60, v/v) for the rapid MPA assay and 30:70 for the simultaneous MPA and
MPAG assay. The assays were linear over the ranges 0.1 to 50.0 mg/l for MPA and
2.8 to 225.8 mg/l for MPAG. Mean absolute recovery for all analytes was >99%.
These methods are suitable for therapeutic drug monitoring and pharmacokinetic
studies.
PMID- 9653968
TI - Determination of pravastatin in human plasma by high-performance liquid
chromatography with ultraviolet detection.
AB - A sensitive high-performance liquid chromatographic (HPLC) method for the
quantitation of the HMG-CoA reductase inhibitor pravastatin in human plasma is
described. Sample preparation based on reversed-phase solid-phase extraction
using triamcinolone acetonide as internal standard (I.S.). The compounds were
separated on C18 reversed-phase analytical column and then determined by
ultraviolet detection. The recovery of pravastatin from plasma was 69.2+/-6.7%
(mean+/-S.D.). The limit of detection for pravastatin in aqueous solution was 0.4
ng, the limit of quantitation in plasma was 2 ng/ml. In a preliminary
pharmacokinetic study with two healthy volunteers the t1/2 of pravastatin in
plasma was found to be 0.8 and 2.3 h.
PMID- 9653969
TI - Simultaneous determination of the stereoisomers of guggulsterone in serum by high
performance liquid chromatography.
AB - Simultaneous separation of E- and Z-guggulsterone, which is the main ingredient
of 'Guggulip', an ayurvedic drug, was accomplished by HPLC on a C18 column using
methanol, acetonitrile, buffer and tetrahydrofuran as a mobile phase. The
compounds were monitored at 248 nm on a photodiode array detector. The assay
method was used for the simultaneous determination of stereoisomers (E and Z) of
guggulsterone in spiked serum and dosed (50 mg/kg, p.o.) rats. The recoveries of
E- and Z-isomers from serum samples were always greater than 90%. The calibration
graph was linear over the range of 25-2500 ng/ml for Z- and E-isomers. Lowest
quantitation limit of Z- and E-guggulsterones was 25 ng/ml.
PMID- 9653970
TI - Determination of flufenamic, meclofenamic and mefenamic acids by capillary
electrophoresis using beta-cyclodextrin.
AB - The possibility of separating flufenamic, meclofenamic and mefenamic acids by
capillary electrophoresis was studied. The best approach involved combining a
suitable pH of the carrier electrolyte (pH 12.0) with the host-guest complexation
effects of beta-cyclodextrin. A running buffer consisting of 30 mM phosphate
buffer (pH 12.0), 2 mM beta-CD and 10% (v/v) acetonitrile was found to provide a
very efficient and stable electrophoresis system for the analysis of fenamic
acids by capillary zone electrophoresis. Responses were linear from 0.4 to 40
microg/ml for the three drugs with detection limits of about 0.3 ng/ml. Intra-
and inter-day precision values of about 1-2% R.S.D. (n = 11) and 3-4% R.S.D. (n =
30), respectively, were obtained. The method is highly robust and no breakdowns
of the current or capillary blockings were observed for several weeks. The
general applicability of this rapid CZE procedure (migration times less than 12
min) is demonstrated for several practical samples, including serum, urine and
pharmaceuticals.
PMID- 9653971
TI - Comparison of chiral recognition capabilities of cyclodextrins for the separation
of basic drugs in capillary zone electrophoresis.
AB - The enantiomeric separation of some racemic anti-histamines and anti-malarials,
namely (+/-)-pheniramine, (+/-)-brompheniramine, (+/-)-chlorpheniramine, (+/-)
doxylamine, and (+/-)-chloroquine, was investigated by capillary zone
electrophoresis. The enantiomeric separation of five compounds was obtained by
addition of approximately 7 mM (1%, w/v) sulfated-beta-cyclodextrin into the
buffer as a chiral selector. The effects of sulfated-beta-cyclodextrin
concentration and buffer pH on migration and resolution are discussed. Two other
cyclodextrins, carboxyethylated-beta-cyclodextrin and hydroxypropyl-beta
cyclodextrin were also investigated. Four of the racemic compounds were resolved
using 14 mM (2%, w/v) carboxyethylated-beta-cyclodextrin while 28 mM (4%, w/v)
hydroxypropyl-beta-cyclodextrin resolved only two of them. It was found that the
type of substituent and the degree of substitution on the rim of the CD structure
played an important role in enhancing the chiral recognition. Cyclodextrins with
negatively charged substituents and higher degree of substitution on the rim of
the structure proved to give better resolution to the cationic racemic compounds
compared with cyclodextrin with neutral substituents. This is due to the
countercurrent mobility of the negatively charged cyclodextrin relative to the
cationic analytes thus allowing for a smaller difference in interaction constants
to achieve a successful resolution of enantiomers. Furthermore, lower
concentrations of negatively charged cyclodextrins were necessary to achieve the
equivalent resolutions as compared with the neutral ones.
PMID- 9653972
TI - Investigation of the stereoselective metabolism of praziquantel after incubation
with rat liver microsomes by capillary electrophoresis and liquid chromatography
mass spectrometry.
AB - Two different separation methods for the antischistosomal drug praziquantel and
its metabolites by capillary electrophoresis are described. Achiral separation
was obtained by micellar electrokinetic capillary chromatography using sodium
dodecyl sulfate as micelle-forming surfactant. On the other hand, the negatively
charged sulfobutylether-beta-cyclodextrin as a chiral selector enabled the
separation of the drug and its metabolites as well as their enantioseparation.
Based on this separation, the enantioselectivity of the metabolism of
praziquantel was studied by incubation of the drug with rat liver microsomes.
Whereas trans- and cis-4-hydroxypraziquantel were mainly formed from the R-(-)
enantiomer, another, different monohydroxylated metabolite was only formed from
the S-(+)-enantiomer. Information about the structure of these metabolites was
obtained, using LC-MS.
PMID- 9653973
TI - Determination of metformin in plasma by capillary electrophoresis using field
amplified sample stacking technique.
AB - A capillary electrophoresis method was described for the determination of
metformin in human plasma based on the extraction of the ion-pair with
bromothymol blue into chloroform. Phenformin was used as internal standard. Field
amplified sample stacking injection was employed with an electrokinetic injection
voltage of 10 kV for 10 s. The running buffer was 0.1 M phosphate buffer (pH
2.5), running voltage was 20 kV and the UV absorbance detection was set at 195
nm. The limit of quantitation was 0.25 microg/ml. Linearity range of calibration
curve was 0.25 to 3.5 microg/ml. Recoveries for three levels (0.25, 1 and 2
microg/ml) were 80.24%, 67.44% and 58.97% (n = 5 for each level), respectively.
The intra-day precisions for the three levels were 11.9%, 3.09% and 4.33% and the
inter-day precisions were 12.4%, 4.57% and 4.94%, respectively. The
concentrations of metformin hydrochloride in human plasma of eight volunteers
were measured after orally administrating metformin enteric-capsule and tablet.
PMID- 9653974
TI - Determination of gamma-glutamylglutathione and other low-molecular-mass
biological thiol compounds by isocratic high-performance liquid chromatography
with fluorimetric detection.
AB - A method was developed for the simultaneous determination of gamma
glutamylglutathione (gamma-GluGSH) and other low-molecular-mass thiol compounds
(cysteine, cysteamine, homocysteine, cysteinylglycine, gamma-glutamylcysteine,
glutathione and N-acetylcysteine) using high-performance liquid chromatography
combined with precolumn fluorescence labeling with ammonium 7-fluorobenzo-2-oxa
1,3-diazole-4-sulphonate (SBD-F). These SBD-labeled thiol compounds were
separated within 35 min on a Cosmosil 5C-18AR column with isocratic elution using
75 mM sodium citrate buffer (pH 2.90)-methanol (98:2) and detected
fluorimetrically (ex. 386 nm, em. 516 nm). The calibration graphs using 2
mercaptoethanol as an internal standard showed good linearity in the range from
20 pmol to 10 nmol for all thiol compounds examined. The application of this
method for the quantitative determination of thiol compounds in the urine from
gamma-glutamyl transpeptidase-deficient mice was also demonstrated. This method
is sufficiently simple, rapid and sensitive for the determination of gamma-GluGSH
and other low-molecular-mass thiol compounds in biological samples.
PMID- 9653975
TI - High-performance liquid chromatographic method for measurement of cytochrome P450
mediated metabolism of 7-ethoxy-4-trifluoromethylcoumarin.
AB - An HPLC method for analysis of deethylation of 7-ethoxy-4-trifluoromethylcoumarin
(ETFMC), a substrate of various enzymes of the cytochrome P450 superfamily, was
developed. ETFMC was incubated at 37 degrees C with human hepatic microsomes or
microsomes prepared from a lymphoblastoid cell line that expresses human CYP2B6.
Under these conditions, the highly fluorescent metabolite 7-hydroxy-4
trifluoromethylcoumarin (HTFMC) is formed. The metabolite was analyzed by
reversed-phase HPLC with fluorescence detection. The limits of detection of the
metabolite were 5.0 fmol per injection, a sensitivity at least one order of
magnitude greater than the standard method, which does not involve HPLC. This
method will be of great utility when quantities of microsomal protein from cell
lines expressing human CYP enzymes are limited.
PMID- 9653976
TI - Separation of microsomal cytochrome b5 via phase separation in a mixed solution
of Triton X-114 and charged dextran.
AB - The successful introduction of a charged dextran into the Triton X-114 phase
separation system for the selective extraction of cytochrome b5 (cyt. b5) in
liver microsomes is described. In the absence of charged dextran, 55% of total
microsomal proteins and 84% of cyt. b5 were extracted into the surfactant-rich
phase. In the presence of anionic dextran sulfate, the extractability of total
microsomal proteins was greatly reduced while that of cyt. b5 was increased.
After triplicate extraction, cyt. b5 was purified more than 10-fold from
microsomes with a recovery of 91% in the surfactant-rich phase. In view of its
operational simplicity, this method provides a good means for the partial
purification of cyt. b5 prior to chromatographic separations.
PMID- 9653977
TI - Gas chromatographic-mass spectrometric identification and quantitation of benzyl
alcohol in serum after derivatization with perfluorooctanoyl chloride: a new
derivative.
AB - Benzyl alcohol is commonly used as an antibacterial agent in a variety of
pharmaceutical formulations. Several fatalities in neonates have been linked to
benzyl alcohol poisoning. Most methods for measuring benzyl alcohol
concentrations in serum utilize direct extraction followed by high-performance
liquid chromatography. We describe here a novel derivatization of benzyl alcohol
using perfluorooctanoyl chloride after extraction from human serum for analysis
by gas chromatography-mass spectrometry (GC-MS). The derivative was eluted at a
significantly higher temperature respective to underivatized molecule and the
method was free from interferences from more volatile components in serum and
hemolyzed specimens. Another advantage of this derivatization technique is the
conversion of low-molecular-mass benzyl alcohol (Mr 108) to a high-molecular-mass
derivative (Mr 504). The positive identification of benzyl alcohol can be
achieved by observing a distinct molecular ion at m/z 504 as well as the base
peak at m/z 91. Quantitation of benzyl alcohol in human serum can easily be
achieved by using 3,4-dimethylphenol as an internal standard. The within run and
between run precisions (using serum standard of benzyl alcohol: 25 mg/l) were
2.7% (mean=24.1, S.D.=0.66 mg/l, n = 8) and 4.2% (mean=24.3, S.D.=1.03 mg/l, n =
8), respectively. The assay was linear for the serum benzyl alcohol
concentrations of 2 mg/l to 200 mg/l and the detection limit was 0.1 mg/l. We
observed no carry-over (memory effect) problem in our assay as when 2 microl
ethyl acetate was injected into the GC-MS system after analyzing serum specimens
containing 200 mg/l of benzyl alcohol, we observed no peak for either benzyl
alcohol or the internal standard in the total ion chromatogram.
PMID- 9653978
TI - Rapid and simple chromatographic method for the determination of diazepam and its
major metabolites in human plasma and urine.
AB - A simple, rapid, sensitive and selective HPLC method has been developed for the
analysis of diazepam (DZP) and its major metabolites, N-desmethyldiazepam
(DMDZP), temazepam (TZP) and oxazepam (OZP), in plasma and urine, using
clonazepam (CZP) as the internal standard and chloroform as the extracting
solvent, with a 10 ng/ml limit of quantitation for the four assayed drugs, and an
average (+/-S.D.) recovery of 87.7+/-6.46%, 92.9+/-5.31%, 91.4+/-4.01% and 91.7+/
2.68% for DZP, DMDZP, TZP and OZP, respectively (from plasma), and 89.6+/-2.26%,
90+/-4.24%, 87.45+/-0.64% and 94.50+/-0.71% for DZP, DMDZP, TZP and OZP,
respectively (from urine). The method has also proved to be selective and
reproducible.
PMID- 9653979
TI - Determination of ethambutol in plasma by high-performance liquid chromatography
after pre-column derivatization.
AB - A new HPLC assay using UV detection (200 nm) was developed to determine
ethambutol (EMB) concentrations in plasma. Following extraction (0.1 ml plasma)
with chloroform, EMB and octylamine (used as internal standard) were derivatized
with phenylethylisocyanate. Quantitation in plasma was achieved at 200 nm. There
were no interferences from endogenous compounds. Intra- and inter-day
variabilities were lower than 5.2 and 7.6%, respectively. The limit of
quantitation of the method was 0.2 microg/ml. In plasma, ethambutol was found to
be stable for at least one month when samples were stored at -20 degrees C. This
assay was applied to the therapeutic monitoring of EMB concentrations in 19
patients suffering from tuberculosis.
PMID- 9653980
TI - Chromatographic studies on the isolation of peroxydisulphate oxidation products
of primaquine.
AB - Eight compounds from peroxydisulphate oxidation of primaquine were fractionated
on Bio-Gel P-2 column using water as an eluent. A HPLC method employing
acetonitrile-methanol-1 M perchloric acid-water (30:7:1:95, v/v) as a mobile
phase at 1.0 ml/min on microBondapak reversed-phase column and UV detection at
254 nm was developed for the separation and identification of different oxidation
products of primaquine. A combination of Bio-Gel chromatography with reversed
phase HPLC was found to be the most suitable analytical technique for the
semipreparative isolation of various products formed from the oxidation. Two
oxidation products that were isolated had three or four times higher
gametocytocidal activity as compared to primaquine.
PMID- 9653981
TI - Colorimetric determination of hydroxyurea in human serum using high-performance
liquid chromatography.
AB - A high-performance liquid chromatography assay for hydroxyurea in human serum was
developed based on a commercial colorimetric assay kit for urea (Sigma
Diagnostics). Serum (0.5 ml), spiked with methylurea as an internal standard, was
treated with 70% perchloric acid. Supernatant (0.2 ml) was combined with 0.7 ml
of BUN acid reagent and 0.6 ml of BUN color reagent. The resulting colored
reactant (100 microl) was analyzed on a 300 x 3.9 mm Bondclone 10 C18 column
coupled with a UV-Vis detector, at 449 nm. The mobile phase was 13% acetonitrile
in water. Retention times of colored derivatives of hydroxyurea and methylurea
were 6.5 and 12.2 min, respectively. The log-log calibration curve was linear
from 0.0065 to 1.31 mM. Average accuracy was 99.9+/-4.0% and the intra- and inter
day error of assay did not exceed 11%.
PMID- 9653982
TI - High-performance liquid chromatographic determination of propiverine and its N
oxide in human serum.
AB - A high-performance liquid chromatographic method has been developed for the
determination of propiverine hydrochloride (P4) and its main metabolite,
propiverine N-oxide (P4NO) in human serum. P4 has been shown to be efficacious in
those patients who have either idiopathic bladder instability, or neurogenic
bladder (detrusor hyperflexia) resulting from spinal cord injuries. In the
present method, the analytes were extracted from serum (1 ml, pH 8) into methyl
tert.-butyl ether. The separation was performed on a reversed-phase C8 (RP-select
B) column using phosphate buffer-acetonitrile (30:70, v/v). UV absorption was
used for measuring the analytes, with a limit of quantitation of about 10 ng/ml,
which is appropriate for pharmacokinetic studies.
PMID- 9653983
TI - Direct enantioseparation of some beta-adrenergic blocking agents using
impregnated thin-layer chromatography.
AB - The resolution of (+/-)-atenolol, (+/-)-propranolol and (+/-)-metoprolol into
their enantiomers was achieved by TLC on silica-gel plates impregnated with
optically pure L-lysine (0.5%) and L-arginine (0.5%) as the chiral selectors. In
all cases, different combinations of acetonitrile-methanol solvent systems were
found to be successful in resolving these compounds. Spots were detected using
iodine vapour. The detection limit for both (+/-)-atenolol and (+/-)-propranolol
was 2.6 microg and for (+/-)-metoprolol, it was 0.26 microg.
PMID- 9653984
TI - Simple and fast chromatographic method for the determination of sotalol in human
serum.
AB - We developed a method for the determination of sotalol in human plasma. After a
simple deproteinization of the sample, we submit the supernatant to high
performance liquid chromatography with fluorescence detection. A few minutes are
necessary to complete the analysis.
PMID- 9653985
TI - Determination of immuno-cross-reactivity between Cryptosporidium parvum and
Eimeria spp.
AB - Immuno-cross-reactivity between Cryptosporidium parvum and Eimeria spp. was
studied by the indirect fluorescent antibody test (IFAT) and Western blot
procedure. Thirty-seven sera from asymptomatic (non-diarrheic) cattle, with known
coprological (presence-absence of coccidia) and serological data respecting C.
parvum, were tested by IFAT using Eimeria oocysts as antigen. Most sera (54%)
displayed immunofluorescence around the surface of the Eimeria oocysts.
Simultaneously, serum samples from rabbits naturally infected with Eimeria spp.
(E. magna, E. intestinalis and E. residua), but free of C. parvum infection, were
used to investigate the recognition of C. parvum oocyst antigens by the Western
blot procedure. Fractions in the 11.5-94 kDa range, as well as others with
molecular masses over 94 kDa, were recognized by sera from rabbits. Sera
collected during patency period showed low or moderate reaction with antigenic
fractions in the 11.5-25 kDa range. However, 29, 58 and 71 to 75 kDa proteic
fractions were moderately or strongly recognized even after rabbits finished
oocyst excretion.
PMID- 9653986
TI - Detection of Blastocystis sp. in domestic dogs and cats.
AB - Blastocystis sp. was detected in faecal samples from domestic dogs and cats in
Brisbane, Australia. The prevalence rates were high, with 70.8% of the dogs and
67.3% of the cats infected with this organism. Blastocystis sp. from faecal
material from two dogs was successfully cultured on inspissated egg slant medium
for several months, but could not be maintained for longer periods. Blastocystis
sp. from feline faecal samples failed to grow in culture. The parasites found in
dogs and cats were generally smaller than Blastocystis hominis from human faecal
material, and were the vacuolar form rather than the multivacuolar form.
Otherwise, the general morphology of these organisms appeared similar to B.
hominis when examined by light and transmission electron microscopy.
PMID- 9653987
TI - Ultrastructure of Babesia bigemina gametes obtained in "in vitro" erythrocyte
cultures.
AB - Propagation of Babesia bigemina in "in vitro" erythrocyte cultures resulted in
the appearance of the sexual stage of the parasite, characterized by cytoplasmic
projections and microtubules. These morphologically distinct parasites were found
to adhere to each other, with later fusion of their membranes. No nuclear fusion
was observed. The ultrastructure of the sexual stages was described.
PMID- 9653988
TI - The safety and efficacy of Australian tick-borne disease vaccine strains in
cattle in Paraguay.
AB - Glycerol preserved, frozen tick-borne disease vaccine strains developed in
Australia were imported into Paraguay to test their safety in pregnant Holando
heifers and their efficacy against challenge from inoculated local field strains
of Babesia bigemina, B. bovis and Anaplasma marginale in Hereford X Criolla
heifers. The two Babesia strains proved to be safe and the B. bovis K strain was
very effective in providing immunity to a local field strain of B. bovis. The B.
bigemina efficacy trial was inconclusive, possibly due to the avirulent nature of
the local field strain used in challenge. The A. centrale strain did not prove to
be as safe as would be desirable in safety trials, neither did it provide as good
protection as the Babesia strains in the efficacy trial. It was concluded that
the Babesia strains provided good protection against field challenge in Paraguay
and were safe to use in highly susceptible cattle, however an alternative to A.
centrale should be sought to provide protection against local strains of A.
marginale.
PMID- 9653989
TI - Interaction of chicken anaemia virus and Cryptosporidium baileyi in
experimentally infected chickens.
AB - The natural occurrence of concomitant chicken anaemia virus (CAV) and
Cryptosporidium baileyi infection was described earlier. In this experiment, 1
day-old chickens were infected with CAV alone (anaemia virus infected, AI) or
followed by inoculation with 8 x 10(5) C. baileyi oocysts orally at 1 wk of age
(anaemia virus and Cryptosporidium infected, ACI). Another group of chickens
received the same dose of C. baileyi oocysts without previous virus infection
(Cryptosporidium infected, CI), and two groups of uninfected chickens served as
controls. Except one group (uninfected control, UC), all groups -- including the
other control group (challenged control, CC) -- were challenged with an oral
inoculum of 8 x 10(5) C. baileyi oocysts at the age of 4 wk. Haematological,
serological, immunohistochemical and pathological findings confirmed the effect
of the virus agent. The individual C. baileyi oocyst shedding did not show
significant difference between group CI and ACI, however, after challenge
infection the AI chickens shed approximately three times more C. baileyi oocysts
than those in group CC. Mortality and the percentage of birds that developed
anaemia was significantly higher among ACI than AI chickens, while haematocrit
values at 2 wk of age and relative bursal weights at 4 wk of age were moderately
lower in the ACI group. The results presented here suggest that concurrent CAV
infection increases the reproductive potential of C. baileyi in chickens, and
both pathogens have synergistic effect on each other.
PMID- 9653990
TI - Pharmacokinetics and efficacy of long-term low-level administration of
triclabendazole in urea molasses blocks against induced bovine and bubaline
fasciolosis.
AB - The pharmacokinetics and flukicidal efficacy of triclabendazole delivered in low
doses on a daily basis through urea molasses blocks were studied in cattle and
buffaloes experimentally infected with Fasciola gigantica. The observations were
compared with single therapeutic doses at 12.0 and 24.0 mg/kg body weight in
cattle and buffaloes, respectively, prior to becoming experimentally infected.
After receipt of triclabendazole by cattle and buffaloes at 0.83 and 3.0 mg/kg
body weight, respectively, on a daily basis, both the animal species exhibited
equilibrium between its absorption and disposition of its metabolites in plasma
on day 4 and remained almost unchanged thereafter. The continuous subtherapeutic
dosing of triclabendazole through urea molasses block at 0.83 mg/kg body weight
in cattle and 3.0 mg/kg body weight in buffalo proved to be efficacious against
mature liver flukes.
PMID- 9653991
TI - Observations on the Echinococcus granulosus horse strain in Spain.
AB - The Spanish sheep and horse strains of Echinococcus granulosus possess several
differential characteristics in their metacestode stage. Cysts from sheep vary
widely in size and fertility, but they usually have a thin cyst wall and, when
fertile, a whitish hydatid sand formed by brood capsules and protoscoleces. Two
types of infections have been observed in horses: one resembling that of sheep,
caused by small, non-fertile cysts with a thin wall, and a second type caused by
medium to large, always fertile cysts with a thick wall. In this latter case,
hydatid sand is always dark brown in color and formed mainly by brood capsules
(with almost no free protoscoleces) and abundant calcareous corpuscles. These
characteristics of the fertile equine cysts, which were identified in other
studies by genetic, biochemical, immunological and physiological criteria as
belonging to the horse strain, have not been previously described nor observed in
cysts from other host species. It is considered that the horse strain possesses a
strong intermediate host specificity.
PMID- 9653992
TI - Taenia solium cysticercosis in young pigs: age at first infection and
histological characteristics.
AB - In spite of the vast knowledge that exists in the fields of immunology,
biochemistry, diagnosis and treatment, the basic facts about the dynamics of the
transmission of Taenia solium are incomplete. The present study determines the
age at which piglets become infected in a rural community of Mexico, where the
climate is divided into the dry and rainy seasons. It was found that piglets
become infected during the dry months, not so during the rainy season. They pick
up eggs at the age of 2 to 4 weeks and the metacestodes are present in the liver.
In older animals aged 4 to 6 months, the larvae were also found in the muscles.
In a 6-month-old pig larvae were found in the muscles and brain. These findings
may be explained by behavioural studies of free living pigs and climatic
conditions.
PMID- 9653993
TI - The effect of repeated moves to clean pasture on the build up of gastrointestinal
nematode infections in calves.
AB - The build up of gastrointestinal nematode infections was followed in two grazing
experiments. Both experiments included four groups of six calves, a permanently
housed non-infected control group and three groups which were grazed from May to
October. One of these was moved to aftermath in the beginning of July, the second
in the beginning of July and August and the third in the beginning of July,
August and September. The build up of gastrointestinal nematode infections was
followed by performing faecal egg counts, differentiation of faecal larval
cultures, pasture larval counts, serum pepsinogen values, serum antibodies
against Cooperia oncophora, weight gain and worm counts. In the second experiment
four of the principal trial animals of each group were treated with oxfendazole
and subsequently challenged with 100,000 larvae of Ostertagia ostertagi to
examine development of immunity against O. ostertagi. The faecal egg counts and
the worm counts of the sentinels necropsied in July indicated low initial
infections in both experiments. Infection levels in experiment 1 remained low in
each group until the beginning of September. However, during the last month,
moderate to high infections were acquired by the groups which were moved once or
twice. In contrast, low to moderate infections were maintained in the group moved
three times. In the second experiment moderate C. oncophora burdens were already
observed in the sentinels grazed until the beginning of August. Tracers grazing
in August-September with the group moved once acquired high O. ostertagi and C.
oncophora infections, whereas those grazed with both other groups acquired
moderate infections. In October high infections with both species occurred in the
groups moved once and twice, whereas low to moderate infections were observed in
the group moved three times. The challenge infection demonstrated a reduction of
establishment of O. ostertagi of approximately 70% in all three groups on
pasture. The results demonstrate that moving calves at monthly intervals to clean
pasture can be an effective method for the control of parasitic gastroenteritis.
In addition, the data indicate that it is essential that the last move does not
occur more than 1 month before the end of the grazing season.
PMID- 9653994
TI - Pathogenicity and immunogenicity of different isolates of Teladorsagia
circumcincta.
AB - The effects on liveweight gain and development of immunity were studied in lambs
trickle infected for 8 weeks with either a benzimidazole-resistant isolate
(Moredun ovine resistant isolate, MORI), a multiple benzimidazole + ivermectin
resistant isolate (Moredun caprine resistant isolate, MCRI) or an unselected
susceptible isolate (Moredun ovine susceptible isolate, MOSI) of Teladorsagia
circumcincta. Plasma pepsinogen concentrations of infected groups were
significantly elevated compared to an uninfected control group (P < 0.001) by day
14. The liveweight gains varied markedly but there were no statistical
differences between the infected and uninfected control groups at any point in
time during the study. Lambs infected with the MORI had significantly lower
faecal consistency scores than the other challenged groups on days 7 and 14 (P <
0.05) but from day 21 onwards, faecal consistencies were similar in all of the
groups. There was a notable difference in the pre-patent periods of the different
isolates with the MOSI producing positive faecal egg counts (FECs) by day 14 of
the study. The FECs remained reasonably low once infections had reached patency
and there were no further differences between the groups. Following
administration of anthelmintic to remove residual worms from the trickle
infection, no differences between the infected groups in terms of worm burden or
mucosal mast cell numbers were evident as a consequence of a single challenge
infection. The changes in genetic code associated with enhanced resistance
against anthelmintics do not appear to have resulted in any fundamental
alteration of the pathogenicity and immunogenicity of these three isolates of
Teladorsagia.
PMID- 9653995
TI - Efficacy of ivermectin delivered from a sustained-release bolus against
gastrointestinal nematodes in field grazing calves in Nyandarua district of
Kenya.
AB - The effect of ivermectin delivered by an orally administered prototype sustained
release (IVM SR) bolus was evaluated over a period of 140 days using 12 steers
aged approximately 8-10 months and ranging in weight from 150 to 175 kg. They
were allocated to two groups of 6 steers each by restricted randomization based
on their liveweight. Each of the treatment group received an IVM SR bolus
designed to deliver 12 mg of the ivermectin/day for 135 days. The other group was
designated as non-medicated controls. The groups were placed on adjacent 3 acre
paddocks obtained by sub-dividing of 6.0 acre permanent pasture which had
previously been grazed by young untreated cattle so exposing experimental steers
to a similar challenge of a contaminated paddock. The faecal egg counts, herbage
larval counts and worm burdens of the major gastro-intestinal nematodes of cattle
were significantly reduced by the use of the IVM SR boluses. These
parasitological effects were reflected in the increased liveweight gains in the
IVM SR bolus-treated steers. The control steers required occasional salvage
treatments over the trial period and the herbage on their paddock was heavily
contaminated with infective larvae as reflected in the high worm burden in the
control steers necropsied at trial termination and in tracer calves introduced
into the paddocks during the initial (Day 31), interim (Day 69) and final (Day
100) stages of the experiment.
PMID- 9653996
TI - The potential of nematophagous fungi to control the free-living stages of
nematode parasites of sheep: studies with Duddingtonia flagrans.
AB - The nematophagous fungus, Duddingtonia flagrans, isolated from a fresh sheep
faecal sample obtained from a farm in northern New South Wales, Australia, was
subjected to a number of in vivo investigations in both surgically modified and
normal sheep to determine its capacity to survive passage through the
gastrointestinal tract. Single and sustained dosing experiments established that
between 5 x 10(5) and 10(6) chlamydospores/day resulted in a substantial (> 80%)
reduction in the number of infective larvae derived from nematode eggs in faeces.
This effect can be maintained if dosing continues. These results demonstrate for
the first time the potential of nematophagous fungi to be deployed by means of
sustained release technology in the biological control of nematode parasites of
livestock.
PMID- 9653997
TI - The potential of nematophagous fungi to control the free-living stages of
nematode parasites of sheep: pasture plot study with Duddingtonia flagrans.
AB - The potential of nematophagous fungi to control the free-living stages of
nematode parasites of sheep: Pasture plot study with the fungus Duddingtonia
flagrans. Vet. Parasitol. The experiment was designed to test the ability of D.
flagrans to reduce infective larval populations on pasture after passage through
the gastrointestinal tract of sheep. Merino sheep were given chlamydospores by
intra-ruminal infusion at a rate of 5 million chlamydospores/sheep/day and faeces
collected from these sheep was deposited on pasture plots. Numbers of larvae
recovered from faeces and pasture were both lower on plots from sheep dosed with
fungus (P < 0.001 and P < 0.01, respectively) than on plots from control sheep.
PMID- 9653998
TI - The relationship between parasite counts, lesions, antibody titres and daily
weight gains in Psoroptes ovis infested cattle.
AB - Psoroptes ovis counts, extent of lesions (clinical index: ClinI), daily weight
gains (DWGs) and anti-P. cuniculi antibody titres in ELISA were recorded during
seven therapeutic field trials. Relationship between these different data were
studied. The differences between the mean DWG of treated and untreated control
animals of the different trials ranged from 39 to 1206 g/day. Data were pooled
for statistical analysis and the influence of trial conditions (management of the
herd, farm, treatment) was extracted from each individual data by subtracting,
from the DWG of each animal, the mean DWG of its trial. Such data were called
daily weight gain over the trial mean (DWG/TM). Multiple regression of DWG/TM,
calculated over the period between the clinical examinations in control animals
(n = 40), on clinical indices and sex demonstrated a significant DWG/TM reduction
per percentage of affected body surface according to the following equation:
DWG/TM (in g/day)= 135-22 ClinI(0)-13 ClinI(28/35)-70 (if male) (R2 adjusted =
0.39), where ClinI(0) and ClinI(28/35) are the clinical indices recorded
respectively at the beginning (day 0) and at the end (day 28 or 35) of the
experimental period during which the animals were left untreated. A
nonsignificant relationship (R2 adjusted = 0.07) was found between the antibody
titres on day 28 or 35 and the individual DWG/TM This would suggest that serology
could be used to estimate the prevalence of the disease on a local or national
basis but not to calculate its economic impact.
PMID- 9653999
TI - Biometrical alterations of Trypanosoma evansi isolate in laboratory rodents.
AB - Biometrical alterations in a horse Trypanosoma evansi isolate were observed when
passaged in laboratory rodents. The major parasite transformation observed was
the increase in the total length as a consequence of an increase in some parasite
measurements. These transformations probably occurred as a consequence of a host
change from horse to rodents. No kinetoplastic forms were observed.
PMID- 9654000
TI - Outbreaks of trypanosomosis due to Trypanosoma vivax in cattle in Bolivia.
AB - This paper reports the first occurrence of bovine trypanosomosis due to
Trypanosoma vivax in Bolivia. T. vivax was identified in thin blood smears of 159
cattle from the Provinces of Velaco (57), Nuflo de Chavez (20), Guayaros (30) and
Chiquitos (52), and in 86.20% of 29 cattle from Laguna Concepcion examined by
microhematocrit test. The clinical signs observed were fever, anemia, abortion,
progressive weakness, loss of appetite, lethargy, substantial weight loss in a
relatively short time, and progressive emaciation.
PMID- 9654001
TI - External anomalies of Anoplocephala perfoliata from remainder of a collection
from equids in Kentucky with notes on Anoplocephala magna.
PMID- 9654002
TI - The development of concepts on development--a dialogue with Antonio Garcia
Bellido. Interview by Enrique Cerda-Olmedo.
PMID- 9654003
TI - Developmental cell lineage.
AB - Studies of the role of cell lineage in development began in the 1870s, fell into
decline in the first half of the 20th century, and were revived in the 1960s.
This revival was attended by the introduction of new and powerful analytical
techniques. Cell lineage can be inferred to have a causative role in
developmental cell fate in embryos in which induced changes in cell division
pattern lead to changes in cell fate. Such a causative role of cell lineage is
suggested also by cases where homologous cell types characteristic of symmetrical
and longitudinally metameric body plan arise via homologous cell lineages. The
developmental pathways of commitment to particular cell fates proceed according
to a mixed typologic and topographic hierarchy, which appears to reflect an
evolutionary compromise between maximizing the ease of ordering the spatial
distribution of determinants of commitment and minimizing the need for migration
of differentially committed embryonic cells.
PMID- 9654004
TI - Creating mosaics in Drosophila.
AB - The ability to create mosaic animals allows the phenotypic analysis of patches of
groups of genetically different cells that develop in a wild type environment. In
Drosophila, a variety of techniques have been developed over the years to
generate mosaics, and in this chapter, I review the techniques that our
laboratory has developed. These include the "Dominant Female Sterile" technique
which allows the analysis of gene functions to oogenesis and embryogenesis; the
"Gal4-UAS" technique which allows the control of where and when specific genes
are expressed; and, the "Positive Marked Mutant Lineages" technique which allows
clones of cells to express a specific reporter gene.
PMID- 9654005
TI - Probing for gene specificity in epithelial development.
AB - We surveyed a total of 228 random insertions of a P[GawB] element to determine
the fraction of regulatory regions in the Drosophila genome that activate gene
expression specifically in follicle cells versus producing more complex patterns
of expression. We monitored the GAL4 expression encoded by this construct in the
ovarian follicle cells by crossing the lines to a strain containing a lacZ
reporter construct. Sixty four per cent of the insertions showed ovarian
expression. To assess the specificity of this expression, 124 of the 228 lines
were crossed to strains containing either an activated form of Armadillo, the
Drosophila homolog of beta-catenin, or an activated form of Torpedo/Egfr, the
Drosophila homolog of the Epidermal Growth Factor receptor, under the control of
GAL4 target sites. The lethality and imaginal disc phenotypes observed in these
crosses suggest that most random insertions cause GAL4 expression in a variety of
tissues. Very few insertions appear to drive expression only in follicle cells.
Although the activated form of Armadillo produced higher frequencies of lethality
and disk phenotypes, expression in the follicle cell epithelium at later stages
of oogenesis did not lead to a visible phenotype. This contrasts with the
dorsalized phenotypes observed in the combination of the same GAL4 lines with the
activated Torpedo construct.
PMID- 9654006
TI - Genetic requirement of epidermal and female germ line cells in Drosophila in the
light of clonal analysis.
AB - Whether the function of a gene is required in a given cell type is often
determined through the analysis of clones homozygous for a mutant allele of the
gene. The clones usually develop following X-ray induced mitotic recombination.
The paper summarizes the conclusions of clonal analyses of different types of
mutations in both the epidermis and the female germ line cells of Drosophila.
Principles of the so called dominant female sterile technique -for the germ line
and the follicle cells- and its use are summarized. Special attention is paid to
the genetic requirement of the female germ line due to its fundamental function
in the regulation of early embryogenesis.
PMID- 9654007
TI - Cell number control and timing in animal development: the oligodendrocyte cell
lineage.
AB - Our studies of oligodendrocyte development in the rodent optic nerve provide
clues as to how cell numbers and the timing of differentiation may be controlled
during mammalian development. Both cell number and the timing of differentiation
depend on intracellular programs and extracellular signals, which together
control cell survival and cell division. As the cells seem to compete for
limiting amounts of both survival signals and mitogens, the levels of these
extracellular signals must be tightly regulated, but it is not known how this is
achieved. The timing of cell-cycle exit, and therefore the onset of
differentiation, seems to depend in part on the progressive accumulation of the
intracellular Cdk inhibitor p27/Kip1, but it is still unclear how the level of
this protein is controlled over time in the dividing cells. The timing of cell
cycle exit is also regulated by thyroid hormone, which, along with other
hormones, seems to coordinate the timing of development in various organs, much
as the timing of the multiple changes in metamorphosis in both vertebrates and
invertebrates is coordinated by hormones. In this sense, one might think of
mammalian development as a prolonged metamorphosis.
PMID- 9654008
TI - The bHLH genes in neural development.
AB - Groups of genes sharing similar motifs may be used at different steps of a same
developmental process. In this review, we discuss the significance of this
phenomenon in the case of the basic Helix-Loop-Helix (bHLH) proteins that are
involved at different steps of the development of the peripheral nervous system
(PNS) of Drosophila.
PMID- 9654009
TI - The achaete-scute complex as an integrating device.
AB - A classical model to study pattern formation is provided by the epidermal sensory
organs (bristles and other sensilla) that cover the body of Drosophila. Many of
these sensory organs (SOs) arise in very constant positions. How are these
positions specified? To a large extent, they are defined by the highly resolved
sites of expression of the proneural genes of the achaete-scute complex (AS-C).
These genes, which confer to cells the capacity to become SO precursors, attain
their resolved patterns of expression by means of many position-specific
enhancers located within the non-transcribed AS-C DNA. Each enhancer drives
expression at one or very few sites. Evidence is growing that the enhancers
interact with combinations of activators and repressors (prepattern) distributed
in partially overlapping domains which are larger than the AS-C expressing sites.
AS-C transcription is activated only at sites with appropriate combinations of
factors. Thus, the AS-C integrates the positional information embodied in the
relatively broad distributions of prepattern factors and creates a sharper and
topographically more precise pattern.
PMID- 9654010
TI - Muscle patterning and specification in Drosophila.
AB - There are obvious differences in the way sense organs and muscles are generated
during Drosophila embryogenesis. For example, all the cells that compose the
final sense organ are derived from a unique cell through a well-established
lineage, whereas each muscle is formed by fusion of myoblasts that belong to two
different populations: a founder cell and a pool of fusion competent cells.
Despite these differences, similar genes and mechanisms appear to be involved in
the generation of the pattern of sense organs and in muscle development. Thus,
the process of specifying individual cells and endowing them with the ability to
initiate neuronal or muscle development, as well as the acquisition of
alternative fates among sibling cells, appear to be under similar genetic control
both in neural and muscle development.
PMID- 9654011
TI - The genetics of the Drosophila achaete-scute gene complex: a historical
appraisal.
AB - The Drosophila achaete-scute complex consists of four genes encoding
transcription factors of the bHLH family. Due to their intricate organization,
these genes have occupied geneticists and developmental biologists for many
years. Here, genetic studies on the complex are discussed from a historical point
of view.
PMID- 9654012
TI - Molecular recapitulation: the growth of the vertebrate retina.
AB - In postembryonic lower vertebrates, the ciliary marginal zone (CMZ) of the retina
is a continuously growing zone in the central nervous system. By studying the
cellular and molecular biology of the cells in this region, we have discovered
that the CMZ can be divided into several zones, from peripheral to central, which
reflect different stages of development of retinal stem cells. Based on the
behavior of the cells and on the genes expressed in different regions, we propose
here that cellular development in the CMZ recapitulates in space what happens in
embryonic retinal development in time.
PMID- 9654013
TI - From pattern to gene, from gene to pattern.
AB - Our understanding of animal development has been revolutionized by genetic
approaches to the identification and isolation of pattern-regulating genes. In
the past several years, fundamental embryological concepts such as morphogenetic
fields, compartments, and organizers have been defined at a molecular level and
visualized in developing animals. Here, I will discuss how the focus on the
regulation and function of genes with dramatic effects on pattern formation,
primarily by through the analysis of gene expression patterns as surrogates of
physical pattern elements, has elucidated gene hierarchies that control
developmental pathways.
PMID- 9654014
TI - Compartment boundaries: where, why and how?
AB - In the 1960's, Garcia Bellido and colleagues uncovered the existence of
developmental compartments in Drosophila. This observation has had a lasting
impact on our understanding of developmental mechanisms in flies and vertebrates.
Here, I review the work that demonstrated the existence of compartments. I then
conjecture on why compartments exist and review the roles of various gene
products in the maintenance of compartment boundaries.
PMID- 9654015
TI - Growth and patterning from the engrailed interface.
AB - The Drosophila wing is divided into anterior and posterior compartments, the
latter characterized by the expression of the engrailed gene. A comparative
analysis is presented here, and suggests that a primary conserved role of
engrailed is to drive growth of limbs along the proximo-distal axis. The Apical
Ectodermal Ridge in vertebrate limbs resembles the Antero/ Posterior compartment
boundary in fly wings, particularly in molecular aspects. Multiple evidence
suggests that the fly wing Antero/Posterior boundary is not the result of
differential cell affinities between all anterior and posterior cells, but
responds to the area of cell communication between anterior and posterior
compartments. Arguments are presented here to support the notion that the
compartment boundary is a consequence of decapentaplegic function in the control
of growth. Patterning, on the other hand, requires the participation of several
genes, among which are engrailed, invected and hedgehog. Finally, regulatory
interactions between en/En-1 and hh/Shh may be significant in the context of
morphogenetic regulation during normal development.
PMID- 9654016
TI - Interactions between Wingless and Notch during the assignment of cell fates in
Drosophila.
AB - A large number of observations suggest that, during Drosophila development there
are close functional interactions between the activity of Notch receptor and that
of a signaling molecule encoded by wingless gene. In this essay, I summarize
these interactions and discuss the possibility that Wingless acts as a ligand for
Notch as part of a switch that is iteratively involved in the assignation of cell
fates during development.
PMID- 9654017
TI - Positioning and differentiation of veins in the Drosophila wing.
AB - Morphogenesis is the process by which structures with characteristic sizes,
proportions and patterns of cell differentiation are generated during the
development of multicellular organisms. How the elaboration of pattern is related
to cell proliferation and growth control is a critical aspect of morphogenesis.
The imaginal discs of Drosophila are a suitable model in which this can be
investigated at cellular and molecular level, and recent genetic and
developmental analysis has identified some of the key genes and mechanisms that
participate in the regulation of their growth and patterning. This review will
focus on the formation of the venation pattern in the adult wing, particularly
on: 1) the subdivision of the wing blade into domains of gene expression that
position the veins, and 2) the cell-cell signaling pathways that participate in
the final differentiation of veins.
PMID- 9654018
TI - Proximo-distal development in the legs of Drosophila.
AB - The appendages of insects and vertebrates develop as extensions of the body wall.
During development, a proximo-distal axis for growth and patterning is created in
each appendage, in order to specify appendage length and allocation of pattern
elements like joints and sensory organs. Here we use the expression of molecular
markers to examine how PD development takes place in the legs of the fruit-fly
Drosophila melanogaster. The data suggest a process of regionalization and
progressive subdivision of an anlage similar to both insect embryonic
segmentation and vertebrate somitogenesis.
PMID- 9654019
TI - Cell proliferation in the attainment of constant sizes and shapes: the Entelechia
model.
AB - The Entelechia model is a generative model of morphogenesis where individual
cells exhibit surface labels that express scalar difference and planar polarity
along two orthogonal axes X and Y. The amount of surface label depends on the
level of Martial (M) gene product within each cell. The model assumes that the
confrontation of cells on both sides of compartment borders causes an increase in
their level of M gene expression. The resulting disparity between the M value of
border cells and that of their neighbors induces the latter to divide. After each
division the daughter cells increase their own M value, and allocate to the best
matching value position. The increase in M value at the borders therefore extends
through the anlage in a cascade of proliferation. The Entelechia condition is
reached when the border cells attain the species-specific maximal M values, and
the value differences between adjacent cells become indistinguishable. Computer
simulations reveal that this model accounts for a variety of observations made on
imaginal discs, e.g., 1) each disc attains a constant size in terms of number of
cells, independently of the growing conditions; 2) clonal restrictions separate
populations of cells which proliferate by intercalar growth; 3) dissociated cells
are capable of reconstructing original patterns upon reaggregation, and 4)
genetic mosaics of morphogenetic mutations show local effects that may differ
depending on the position of the mutant cells in the growing anlage.
PMID- 9654020
TI - Regulatory control of signal transduction during morphogenesis in Drosophila.
AB - Morphogenesis shapes pattern and size during development. The initiation and
propagation of morphogenetic processes is led by the integrated activation of
signaling cascades. Much is known about regulatory control of signaling cascades
in cell culture systems. However, how this regulatory elements act when cells
need to behave coordinately is still unknown territory. The morphogenetic process
of dorsal closure proceeds through changes in cell shape and polarity under the
control of JNK signaling. Amongst other regulatory elements, Puckered, a
Drosophila MAPK phosphatase, is involved in a negative feedback loop that
controls JNK signaling activity. puckered is expressed in many other tissues,
could influence other developmental events and might regulate different signaling
cascades. The negative regulatory control of signal transduction pathways could
be a general mechanism regulating differentiation and morphogenesis.
PMID- 9654021
TI - Cellular polarity, mitotic synchrony and axes of symmetry during growth. Where
does the information come from?
AB - The polarization of cells during development is discussed with relationship to
synchronized cell divisions and lineage restrictions. A tessellation model is
proposed to explain the generation of the precise hexagonal array of ommatidia in
the eye. This model allows the assembly of highly organized structures from
localized cellular interactions. There is no requirement for a precise genetic
description of the adult organism. Instead a sequential set of reiterated
cellular interactions generates increasingly complex structures. The polarity
patterns observed in adult cuticular bristles and hairs reflect accurate control
of the shape of terminally differentiating cells rather than fine-grained
positional information.
PMID- 9654022
TI - Asymmetry and cell fate in the Drosophila embryonic CNS.
AB - Drosophila CNS precursors, neuroblasts, repeatedly divide to produce a large
neuroblast and a smaller GMC. This division is asymmetric with regard to sibling
cell size, mitotic potential and gene expression. Recent work has identified a
number of molecules that show a polarized distribution during neuroblast mitosis:
prospero RNA and Inscuteable, Miranda, Prospero, Staufen, and Numb proteins. The
process of asymmetric localization of proteins and RNAs is cell cycle dependent,
microfilament dependent and coordinated with the positioning of the mitotic
spindle, which results in the unequal distribution of cell fate determinants to a
specific daughter cell at cytokinesis.
PMID- 9654023
TI - Segmentation of the vertebrate hindbrain: a time-lapse analysis.
AB - The chick hindbrain starts from a simple and relatively uniform axis and becomes
segmented into repeating units, called rhombomeres. The rhombomeres become sites
of cell differentiation into specific neurons and the location from which neural
crest cells emerge from the neural tube to form the peripheral nervous system,
which has only been analyzed at distinct time points due to the lack of a method
to watch the neural tube as it is shaped into segments. We have developed a whole
embryo explant culture system in order to study cell and tissue movements with
time-lapse video microscopy. Quantitative analyses of the neural tube during its
segmentation show that not all rhombomeres are shaped by the same mechanism. In
the rostral hindbrain, or first three segments, rhombomeres are shaped by an
expansion in the lateral width of the mid-rhombomere; either a smaller expansion
or a constriction takes place at the rhombomere boundaries. In the caudal
hindbrain, the rhombomere boundaries constrict more than the mid-rhombomere
lateral widths increase or decrease, leading to the shaping of the segments.
Throughout the segmentation process the rostrocaudal lengths of all rhombomeres
remain nearly constant indicating that shape changes are influenced by lateral
expansions and constrictions of the neural tube.
PMID- 9654024
TI - Segmentation and specification in the branchial region of the head: the role of
the Hox selector genes.
AB - Hox genes are segmentally expressed in the developing vertebrate hindbrain,
neural crest cells and pharyngeal arches suggesting an important role in
patterning these structures. Here we discuss the cellular and molecular
mechanisms controlling segmentation and specification in the branchial region of
the head. In addition, based on the recent phenotypical and molecular analysis of
loss-of-function mutants in the mouse, we speculate that Hox genes may act like
Drosophila selector genes in this system.
PMID- 9654025
TI - The bithorax complex: the first fifty years.
PMID- 9654026
TI - From selectors to realizators.
AB - In 1975 Antonio Garcia-Bellido proposed a framework for understanding the
morphogenetic function of homeotic genes in terms of selector genes and
realizator genes. Since then, much has been learnt of the molecular nature and
expression patterns of the Hox selector genes. Our identification of realizator
genes, and our understanding of how specific sets of realizators are activated in
different segments, is still far from complete, however. Here we discuss the
nature of the Hox target genes identified so far and the basis of the target
specificity of Hox gene products.
PMID- 9654027
TI - trithorax and the regulation of homeotic gene expression in Drosophila: a
historical perspective.
AB - Animals homozygous for a spontaneously arising allele of the trithorax (trx) gene
exhibit highly variegated homoeotic transformations of their thoracic and
abdominal segments. This paper retraces the sometimes tortuous history of the
analysis of trx function, from the fortuitous recovery of the first trx allele,
to the present understanding that trx encodes a highly conserved chromatin
binding protein that is required to maintain the expression of the Antennapedia
and Bithorax complex genes.
PMID- 9654028
TI - Homeotic proboscipedia cell identity functions respond to cell signaling pathways
along the proximo-distal axis.
AB - To better understand how the different cell identities composing a segment are
attributed and coordinated under the control of a single homeotic selector gene,
we examined dose-sensitive homeotic phenotypes associated with gain-of-function
and loss-of-function mutations of the homeotic gene proboscipedia (pb; Hox-A2/
B2). We then employed dose-sensitive segment and cell identity phenotypes
resulting from ectopic proboscipedia expression to screen for other interacting
loci. We find that pb, as well as the homeotic loci Ultrabithorax, Sex combs
reduced and Antennapedia, respond to positional information along the proximo
distal axis. This response for pb implicates at least two signal transduction
pathways, those involving Ras1 and Notch.
PMID- 9654029
TI - Implications of the spatial and temporal regulation of Hox genes on development
and evolution.
AB - Nearly 20 years have passed since Ed Lewis revealed the importance of Hox genes
in the specification of different segments in the anterior-posterior axis of the
fly. Pioneering studies by several authors, among others Garcia-Bellido and his
student Gines Morata, helped to elaborate a theory of segmental specification
that was strengthened with the arrival of molecular techniques to the field of
Developmental Biology. The conservation of Hox genes in metazoans at the level of
sequence, function and complex organization has resulted in the export of this
Drosophila theory as a paradigm to interpret the development of axial
specification in organisms less amenable to experimental study. There are two
main ways to interpret how Hox genes work in Drosophila. One considering Hox
genes as "segment identity" factors giving global properties to the segments in
which they are active. Another considering Hox genes as encoding spatially
restricted transcription factors required for a number decisions taken at the
cellular level. Here I use published and unpublished experimental data to
illustrate that early activation of the Hox genes does not establish a gene code
that leads to "segment identity". I will stress the point that Hox expression
patterns develop with the embryo, that there are many genes involved in this
modulation, and that the changing pattern of expression is important to achieve
the final shape of the animal. I will show that, by interpreting Hox gene
function in this way, some apparently paradoxical results in the Hox field can be
answered. Finally, I discuss the implications of dynamic Hox gene expression on
the evolution of segment morphology.
PMID- 9654030
TI - Hox genes, homeosis and the evolution of segment identity: no need for hopeless
monsters.
AB - Significant changes have occurred in the developmental role of Hox genes, even
within groups of arthropods that already have complex body plans and many
different segment types. This is hard to reconcile with the 'selector gene' model
for Hox gene function. Selector genes act as stable binary switches that direct
lineages of cells to adopt alternative developmental fates. This model suggests
that the regulation of selector genes can only evolve through mutations that
alter the identity of whole developmental compartments -in the case of Hox genes,
whole segments. Once segments have evolved distinct morphology and function, such
mutations will result in dramatic homeotic transformations that are unlikely to
be tolerated by natural selection. Thus we would expect the developmental role of
these "master control genes" to become frozen as body plans become more complex.
I argue for a revised model for the role and regulation of the Hox genes. This
provides alternative mechanisms for evolutionary change, that may lead to
incremental changes in segment morphology. The summation of such changes over
long periods of time would result in differences in Hox gene function between
taxa comparable to the effects of gross homeotic mutations, without the need to
invoke the selective advantage of hopeful monsters.
PMID- 9654031
TI - Understanding the genetic basis of morphological evolution: the role of homeotic
genes in the diversification of the arthropod bauplan.
AB - Due to the segmental organization of their body plans, arthropods can be
considered the paradigmatic modular organisms. In the past two decades, genetic
studies of the homeotic (Hox) genes in Drosophila melanogaster have provided
initial insight into the molecular mechanisms that govern the establishment of
segmental identity. In this review, we will address the question of the possible
role of four Hox genes: labial (lab), proboscipedia (pb), Deformed (Dfd), and Sex
combs reduced (Scr) in the morphological evolution of arthropods, particularly
with respect to the evolution of the head and head structures in insects.
Overall, these preliminary studies illustrate the role that some of the Hox genes
expressed in the insect head have played in the morphological evolution of
hexapods and likely arthropods in general.
PMID- 9654032
TI - Genesis versus epigenesis: the odd jobs of the Polycomb group of genes.
AB - Cells need the products of the Polycomb Group of genes (PcG) to keep, through
development, the memory of their genetic determination. The pleiotropic mutant
phenotypes of PcG genes strikingly resemble morphological traits, considered as
taxonomic characters with phylogenetic meaning, used in Dipteran classification.
I argue that spatial modulation of the multimeric complexes formed by PcG
products has played a role or escorted the genesis of species.
PMID- 9654033
TI - Sir Vincent Wigglesworth and the coming of age of insect development.
AB - Sir Vincent Wigglesworth (1899-1994), a founder of the discipline of Insect
Physiology, was a central figure in the emergence of the concept of postembryonic
insect development as sequential polymorphism regulated by endocrine signals. At
a time in mid-century when genetics and developmental physiology were severely
compartmentalized, he made the conceptual linkage with the recognition that
sequential polymorphism must have a genetic basis with gene activation regulated
by internal signals.
PMID- 9654034
TI - Embryonic development as a quasi-historical process.
AB - This essay explores the nature of embryonic development in contrast to other
kinds of processes. Anhistorical processes are highly reproducible and are
therefore subject to standard scientific analysis. Such analyses yield results
that may well apply universally. Euhistorical processes are non-reproducible.
Therefore they are not subject to standard scientific analysis, but are
investigated primarily by retrospective speculation. Information gained from such
analyses is of relatively limited applicability. Embryonic development exhibits
traits associated with both anhistorical and euhistorical processes and is
therefore defined as a quasi-historical process. The quasi-historical nature of
developmental processes places constraints on the nature of the solution we can
hope to obtain for the problem of development, but also provides a means of
exploring the euhistorical process of evolution.
PMID- 9654035
TI - Laws for the dynamics of regulatory networks.
AB - We start our analysis from historical but too seldom quoted papers by Delbruck,
Noveck & Weiner, Cohn & Horibata and Monod & Jacob. We try to show how it became
possible to draw a line coupling cell differentiation to the physical concept of
multistationarity, and the latter to the concept of positive feedback circuits.
Two laws give the minimal logical ingredients required for differentiative and
homeostatic regulations. It is briefly shown how they can be used to treat such
complex dynamics as deterministaic chaos, which, admittedly, does not yet belong
to the corpus of developmental biology. It was taken as a challenge to express
our ideas here in purely verbal terms, avoiding any formal treatment.
PMID- 9654036
TI - Syntagms in development and evolution.
AB - The genetic analysis of segmentation, neurogenesis, appendage formation and other
developmental processes has revealed that the development of Drosophila can be
broken down into discrete elementary operations. Thus development can be viewed
as a stepwise process where each step is driven by a small group of genes working
interactively. Garcia-Bellido proposed that each of these groups be called a
"syntagm". In this review, we will describe a series of developmental syntagms,
and explore the consequences of this discontinuous organization of the
developmental program on evolution.
PMID- 9654037
TI - How is developmental stability sustained in the face of genetic variation?
AB - The number and arrangement of scutellar bristles on the thorax of Drosophila
melanogaster is largely invariant in wild-type stocks. This character therefore
appears to be buffered against changes in phenotype, and has previously been
described as a canalized character. Mutations that do alter this phenotype
increase the variability in bristle number and can reveal otherwise cryptic
genetic differences at other loci. This phenomenon is examined and possible
mechanisms contributing to stability of this developmental event are discussed,
but the notion that the character is canalized is found not to be heuristic.
PMID- 9654038
TI - Seven types of pleiotropy.
AB - Pleiotropy, a situation in which a single gene influences multiple phenotypic
traits, can arise in a variety of ways. This paper discusses possible underlying
mechanisms and proposes a classification of the various phenomena involved.
PMID- 9654039
TI - Making sense of behavior.
AB - Neurobiological evidence shows that, during the development of the nervous
system, inherited behavioral sense is built into the brain with remarkable
fidelity. However the way in which the underlying circuitry and its functional
characteristics are represented in the genome is not well understood. One
response to this is to investigate the machinery of functional development in the
nervous system and to set down in principle how genetic control is exerted at
this level.
PMID- 9654040
TI - Debatable issues. Interview by Alain Ghysen..
AB - This paper reports a discussion between Antonio Garcia-Bellido and Lewis Wolpert
about a number of questions raised by Alain Ghysen. The questions follow, in
reverse order, the subjects dealt with in this issue: first the principles (are
there unifying principles of development?), then questions dealing with evolution
(why are patterns conserved?) and with the homeotic genes (what is their
function?), then the cell biology of development (who is controlling actual
morphogenesis?), and the generation and evolution of patterns (what makes
development so reproducible and how does it change from one species to another?)
and finally about the genetics of cell determination and specification (how does
a cell measure its position?). Obviously the discussion did not provide any firm
answers to any of these questions. Perhaps more importantly, it provides a vivid
picture of two contrasting ways of thinking about developmental problems.
PMID- 9654041
TI - Antonio Garcia-Bellido at Hadorn's laboratory in Zurich.
PMID- 9654042
TI - Antonio Garcia-Bellido in Caltech.
PMID- 9654043
TI - Antonio and Sturt: an interaction.
PMID- 9654044
TI - An exceptional friend.
PMID- 9654045
TI - Serendipity, the principle of limited sloppiness, and neural development.
PMID- 9654046
TI - The genetic logic of Antonio Garcia-Bellido.
PMID- 9654047
TI - In defense of pure science: Antonio Garcia-Bellido.
PMID- 9654048
TI - Regulation of translation initiation factors by signal transduction.
AB - Regulation of eukaryotic translation initiation is a process that requires
collaboration between multiple proteins. The cap-binding factor eukaryotic
initiation factor (eIF)4E, its binding protein 4E-BP1, and the guanine-nucleotide
exchange factor eIF2B play important roles in the regulation of the rate of
protein synthesis. This review describes the regulation of the activity of these
three proteins and the signal-transduction pathways involved therein.
PMID- 9654049
TI - Mitogen-activated protein kinase is involved in epidermal-growth-factor-regulated
protein phosphorylation in nuclear membranes isolated from JEG-3 human
choriocarcinoma cells.
AB - The treatment of highly purified nuclear membranes isolated from JEG-3 human
choriocarcinoma cells with epidermal growth factor (EGF) resulted in an increase
of the receptor autophosphorylation and the phosphorylation of several other
proteins, including 44-kDa, 34-kDa and 24-kDa proteins, and a decrease in the
phosphorylation of a 40-kDa protein. The kinetics of phosphorylation and the use
of RG-13022, a selective inhibitor of EGF-receptor kinase activity, suggested
that receptor activation was necessary for the phosphorylation response of the
other proteins. Tyr was exclusively phosphorylated in the EGF receptor and 24-kDa
proteins, Tyr and Thr were phosphorylated in the 44-kDa protein, and Ser was
phosphorylated in the 34-kDa protein and dephosphorylated in the 40-kDa protein.
The molecular size, Thr/Tyr phosphorylation, immunoprecipitation and enzymatic
activity towards myelin basic protein suggested that the 44-kDa protein was a
mitogen-activated protein (MAP) kinase. The EGF treatment not only increased
phosphorylation but also catalytic activity of MAP kinase and these increases
were prevented by the addition of RG-13022. In summary, this report demonstrates
that target cell nuclei contain EGF receptors, which use the MAP kinase signaling
pathway.
PMID- 9654050
TI - A plant surface protein sharing structural properties with animal integrins.
AB - Using a polyclonal antibody (P23) generated against the human platelet integrin
aIIb beta3 and a FITC-conjugate secondary antibody, fluorescence is observed at
the surface of protoplasts isolated from Arabidopsis thaliana and Rubus
fruticosus. Arabidopsis thaliana cells grown in suspension culture containing P23
and glycylarginylglycylaspartylserine (GRGDS), a synthetic peptide containing the
RGD sequence found in many extracellular matrix adhesive proteins demonstrated
aberrant cell wall/plasma membrane interactions and organization. When
glycoproteins from these plants, purified on a concanavalin A Sepharose 4B, were
subjected to SDS/PAGE and Western blotting, under reduced and non-reduced
conditions, immunoblots probed with P23 revealed bands in both species. A shift
in electrophoretic mobility is observed to different apparent molecular mass when
no reducing agent is present. When purified by immunoaffinity chromatography on
anti-aIIb beta3 Sepharose or Sepharose linked to the synthetic peptide D-Arg-Gly
Asp-Trp, the major antigenic components detected migrate at 30 kDa and 60 kDa in
the first experiment and 60 kDa in the second one. Only the 60-kDa component is
immunodetected with antibodies specific for either the beta3 platelet chain or
the aIIb polypeptide, suggesting the presence of two polypeptides co-migrating.
To address more precisely the structure of this complex in plants, competition
assays were performed. A significant inhibition is observed with CS3 a monoclonal
antibody that interacts with the complexed form aIIb beta3 but not the
dissociated subunits. Further structural similarities with the animal aIIb beta3
complex is demonstrated with Western blotting detection after plant glycoproteins
immunoprecipitation with CS3 in absence or presence of 5 mM EDTA to dissociate
the complex. We also present data on the characterization of a polyclonal
antibody, named AcAt2, raised against Arabidopsis glycocoproteins purified by
affinity chromatography on a D-RGDW column and eluted with the same peptide, that
specifically interacts with the animal aIIb beta3 receptor.
PMID- 9654052
TI - Processing and release of tumor necrosis factor alpha.
AB - Tumor necrosis factor alpha (TNFalpha) is synthesized as a transmembrane
precursor form that is proteolytically processed and released as the soluble
mature form. In human monocytes and monocytic cell lines, the production,
processing, and release of TNFalpha are co-induced by certain activators, such as
lipopolysaccharide. To investigate the mechanism of TNFalpha processing and
release, we established a cell line which constitutively produced TNFalpha, by
transfecting the TNFalpha precursor form cDNA into NIH/3T3 cells. In these cells,
the processing and release of TNFalpha were augmented by phorbol 12-myristate 13
acetate (PMA), mediated through a protein kinase C (PKC) signalling pathway.
Various protease inhibitors were tested and it was found that matrix
metalloproteinase (MMP) inhibitors blocked the processing and release of TNFalpha
both in the absence and presence of PMA. This result is compatible with the
recent reports that MMP are involved in the processing and release of TNFalpha.
In contrast, 3,4-dichloroisocoumarin, N alpha-p-tosyl-L-phenylalanine
chloromethane, iodoacetamide, and o-phenanthroline inhibited the processing and
release of TNFalpha only in the presence of PMA, suggesting that serine proteases
requiring SH for their activity, a combination of serine proteases and cysteine
proteases, or MMP, may be involved in the PKC-mediated induction of TNFalpha
processing and release.
PMID- 9654051
TI - Identification of Man alpha1-3Man alpha1-2Man and Man-linked phosphate on O
mannosylated recombinant leech-derived tryptase inhibitor produced by
Saccharomyces cerevisiae and determination of the solution conformation of the
mannosylated polypeptide.
AB - The production of recombinant leech-derived tryptase inhibitor (rLDTI) by two
different strains of Saccharomyces cerevisiae resulted in the secretion of non
glycosylated and glycosylated rLTDI. Monosaccharide analysis and a-mannosidase
treatment demonstrated that glycosylated rLDTI was exclusively alpha
mannosylated. A trypsin digest of reduced and S-carboxymethylated glycosylated
rLDTI was separated on a reverse-phase HPLC column. Glycopeptides identified by a
combination of matrix-assisted laser desorption mass spectrometry, amino acid
sequence analysis, and monosaccharide analysis revealed the presence of different
glycoforms. It was found that Ser24, Ser33 and Ser36 were partially glycosylated
with a single mannose residue, whereas Thr42 in glycosylated rLDTI from both
strains was fully occupied with manno-oligosaccharides with a degree of
polymerization ranging over 1-3 and 1-13 depending on the yeast strain. In
phosphorylated rLDTI a single phosphate group was predominantly located at the
innermost Man residue of units of mannobiose, mannotriose, mannotetraose and
mannopentaose at Thr42. Oligosaccharides released by alkaline treatment were
reduced by sodium borohydride and separated by high-pH anion-exchange
chromatography on a CarboPac MA1 column, and analyzed by one- and two-dimensional
1H-NMR spectroscopy. Besides the major oligosaccharide Man alpha1-2Man-ol, the
(for yeast protein O-glycosylation) unusual Man alpha1-3Man alpha1-2Man-ol was
determined. The solution conformation of glycosylated rLDTI was investigated by
two-dimensional NMR spectroscopy. Structure calculations by means of distance
geometry showed that glycosylated rLDTI is compactly folded and contained small
secondary structure elements. Analysis of the chemical shifts showed that amino
acids Val32-Ser33, Ser36-Ser39 and Thr42 were affected by the O-mannosylation. In
addition, changes in chemical shift were observed within the beta-hairpin peptide
regions Val13-Ser16 and Gly18-Tyr21 attributed to direct interactions of the
mannose residue at Ser36. Furthermore, the protein-linked oligosaccharides were
spatially grouped in a position opposite of the canonical binding loop.
PMID- 9654053
TI - Biochemical characterization and localization of transglutaminase in wild-type
and cell-death mutants of the nematode Caenorhabditis elegans.
AB - Transglutaminase activity was characterized in extracts of the nematode
Caenorhabditis elegans using a microtiter plate method, and found to be Ca2+
dependent, optimal at pH 8.0, and to be inhibited by EGTA, ammonia, iodoacetamide
and GTP. Monoclonal and polyclonal antibodies raised against human tissue
transglutaminase also inhibited the activity and detected a 61-kDa protein from
the worm lysate. Constitutive expression of the enzyme in the wild-type
intestinal cells was revealed by immunohistochemistry. Potential protein
substrates for the enzyme were found in worm lysates using a biotin-labelled
amine substrate. There is a basal level of protein-bound epsilon(gamma
glutamyl)lysine cross-links, characteristic of transglutaminase activity, formed
in situ in adult wild-type animals. Developmental studies have revealed that the
enzyme activity is highest in adult animals, and relatively higher in L1 larvae
than in other larval stages. As compared to wild types, lower transglutaminase
activity has been measured in lysates of ced-3, ced-4 and ced-9 mutants. Cross
link levels were also low in ced-4 and ced-9 mutants. By contrast, the crosslink
content was high in several phagocytosis mutants. The highest concentration was
found in the ced-5; ced-7 double phagocytosis mutants which carry an extra number
of dead cells during their lifespan. In accordance with this finding, several
transglutaminase-immunopositive cells were found in both the embryos and in the
head of these double phagocytosis mutants. The results suggest that a
transglutaminase is involved in, or related to, the death program of cells in C.
elegans and the expression and crosslinking activity of the enzyme may be
perturbed in some ced mutants.
PMID- 9654055
TI - Engineering of factors determining alpha-amylase and cyclodextrin
glycosyltransferase specificity in the cyclodextrin glycosyltransferase from
Thermoanaerobacterium thermosulfurigenes EM1.
AB - The starch-degrading enzymes alpha-amylase and cyclodextrin glycosyltransferase
(CGTase) are functionally and structurally closely related, with CGTases
containing two additional domains (called D and E) compared to the three domains
of alpha-amylases (A, B and C). Amino acid residue 196 (Thermoanaerobacterium
thermosulfurigenes EM1 CGTase numbering) occupies a dominant position in the
active-site cleft. All alpha-amylases studied have a small residue at this
position (Gly, Leu, Ser, Thr or Val), in contrast to CGTases which have a more
bulky aromatic residue (Tyr or Phe) at this position, which is highly conserved.
Characterization of the F196G mutant CGTase of T. thermosulfurigenes EM1 revealed
that, for unknown reasons, apart from the F196G mutation, domain E as well as a
part of domain D had become deleted [mutant F196G(delta'DE)]. This, nevertheless,
did not prevent the purification of a stable and active mutant CGTase protein (62
kDa). The mutant protein was more similar to an alpha-amylase protein in terms of
the identity of residue 196, and in the domain structure containing, however,
some additional C-terminal structure. The mutant showed a strongly reduced
temperature optimum. Due to a frameshift mutation in mutant F196G, a separate
protein of 19 kDa with the DE domains was also produced. Mutant F196G(delta'DE)
displayed a strongly reduced raw-starch-binding capacity, similar to the
situation in most alpha-amylases that lack a raw-starch-binding E domain.
Compared to wild-type CGTase, cyclization, coupling and disproportionation
activities had become drastically reduced in the mutant F196G(delta'DE), but its
saccharifying activity had doubled, reaching the highest level ever reported for
a CGTase. Under industrial production process conditions, wild-type CGTase
converted starch into 35% cyclodextrins and 11% linear oligosaccharides (glucose,
maltose and maltotriose), whereas mutant F196G(delta'DE) converted starch into
21% cyclodextrins and 18% into linear oligosaccharides. These biochemical
characteristics indicate a clear shift from CGTase to alpha-amylase specificity.
PMID- 9654054
TI - A domain within the tumor suppressor protein APC shows very similar biochemical
properties as the microtubule-associated protein tau.
AB - The tumor-suppressor protein APC (adenomatous polyposis coli) binds to
microtubules and promotes tubulin assembly. In vivo the endogenous APC protein is
mainly localized at the end of microtubules that are involved in active cell
migration. Since most tumor-specific APC gene mutations lead to the loss of the
microtubule binding domain this interaction is assumed to play a crucial role in
tumorigenesis. In this study we show that an APC protein fragment (amino acids
2219-2580) within the C-terminal part is enough to bind to non-assembled tubulin
with high affinity. The binding of APC to tubulin does not lead to an alteration
of the intrinsic GTPase activity of the non-assembled tubulin. The APC protein
induces the tubulin assembly in a fast reaction and below the critical assembly
concentration of tubulin. The APC protein induces the bundling of the assembled
microtubules in a concentration-dependent manner. Regarding its biochemical
properties the analysed APC protein fragment strikingly resembles the members of
the microtubule-associated protein family tau. This analogy may help to
understand the role of the APC protein in the suppression of tumorigenesis.
PMID- 9654056
TI - Thylakoid membranes contain a high-conductance channel.
AB - Ion channels in the thylakoid membrane were investigated by direct patch clamping
on swollen thylakoids. A preparation method has been developed in order to
release osmotically swollen intact thylakoids from pea protoplasts derived from
cotyledons of young Pisum sativum plants. The swollen thylakoids with typical
diameters between 10 microm and 20 microm formed reproducibly high-resistance
seals with patch pipettes. We observed a potassium channel with a main conductant
state of lambda approximately 40 pS and a conductance of lambda approximately 90
pS (in asymmetric 20/100 mM KCl) for the fully open channel. Surprisingly, the
thylakoid membranes also contained a high-conductance channel with a main
conductant state of lambda approximately 620 pS (in asymmetric 20/100 mM KCl),
revealing also higher and lower conductant states. With a different experimental
approach we showed that thylakoids are able to accumulate transiently the
membrane impermeant fluorescent dye Lucifer Yellow which likewise suggests the
presence of a pore-like channel with a diameter large enough to allow permeation
of Lucifer Yellow.
PMID- 9654057
TI - Carnitine palmitoyltransferase II specificity towards beta-oxidation
intermediates--evidence for a reverse carnitine cycle in mitochondria.
AB - Using isolated rat liver mitochondria, in the absence or presence of malonyl-CoA
(an inhibitor of carnitine palmitoyltransferase I), we have found that carnitine
palmitoyltransferase II (CPT II) is active with palmitoyl-CoA as well as with its
beta-oxidation intermediates. A partially purified CPT II fraction from rat liver
mitochondria was shown to be able to convert 3-hydroxypalmitoyl-CoA to 3
hydroxypalmitoylcarnitine, which could be identified by fast-atom-bombardment
mass spectrometry. This apparent broad specificity of CPT II was further
evaluated by kinetic studies using purified CPT II. It was found that CPT II
readily accepts 3-oxopalmitoyl-CoA, palmitoyl-CoA, 3-hydroxypalmitoyl-CoA and 2,3
unsaturated palmitoyl-CoA as substrates with decreasing order of affinity. The
apparent Vmax values found for the first three compounds were of the same order
of magnitude; the 2,3-unsaturated acyl-CoA was the poorest substrate. Kinetic
studies with purified CPT II showed 3-hydroxypalmitoyl-CoA to have the lowest
K0.5 value (20 +/- 6 microM) of all the CoA esters studied; the highest K0.5
value (65 +/- 17 microM) was found for the 3-oxo intermediate. These findings
support the hypothesis that CPT II is involved in the export of toxic long-chain
acyl-CoA esters from the mitochondria by first converting them into the
corresponding carnitine esters, followed by transport out of the mitochondria and
subsequently out of the cell.
PMID- 9654058
TI - Glucocorticoids induce the expression of the leptin gene through a non-classical
mechanism of transcriptional activation.
AB - Leptin is a hormone which is produced in adipose tissue and which plays a role in
the regulation of energy homeostasis. The expression of the ob gene, encoding
leptin, is under multi-hormonal control. We have shown previously that high doses
of glucocorticoids are positive regulators of leptin expression in rats and that
they concomitantly reduce food intake and body mass gain in these animals. In the
present report we analyse the molecular mechanism of this glucocorticoid
regulation of leptin expression. In cultured rat adipocytes dexamethasone induces
leptin mRNA levels, an effect not inhibited by the protein synthesis inhibitor
cycloheximide. In addition, our data indicate that the induction of the
expression of the leptin gene by dexamethasone is at least in part due to a
transcriptional activation that is mediated by the glucocorticoid receptor.
Deletion mapping of the human leptin promoter shows that cis-elements involved in
the glucocorticoid effect are located between -55 and +31 relative to the
transcription initiation site. Since this region does not contain a binding site
for the glucocorticoid receptor, the effect does not rely on the classical
molecular mechanism of glucocorticoid receptor action. A role of C/EBP and Sp-1
in mediating this glucocorticoid effect was furthermore excluded. Multiple
nuclear factors from 3T3-L1 preadipocytes interact with this promoter region of
the human leptin gene and may be potential mediators of the induction by
glucocorticoids.
PMID- 9654059
TI - Dicyclohexylcarbodiimide interaction with the voltage-dependent anion channel
from sarcoplasmic reticulum.
AB - In a recent study [Shoshan-Barmatz, V., Orr, I., Weil, S., Meyer, H., Varsanyi,
M. & Heilmeyer, L. M. G. (1996) FEBS Lett. 386, 205-210] we have demonstrated the
presence of the voltage-dependent anion channel (VDAC) in skeletal muscle
sarcoplasmic reticulum (SR) as supported here by co-localization of VDAC and
(Ca2+ + Mg2+)ATPase in the SR using double-immunogold labeling. The interaction
of the carboxyl-modifying reagent dicyclohexylcarbodiimide with the SR-VDAC is
characterized by labeling with [14C]dicyclohexylcarbodiimide and by
dicyclohexylcarbodiimide modification of the reconstituted-purified VDAC channel
activity. In both SR and mitochondrial membranes, [14C]dicyclohexylcarbodiimide
most specifically labeled a 35-kDa protein, identified as VDAC by specific anti
VDAC Ig. Labeling of the SR-VDAC was about twofold higher than that of the
mitochondrial VDAC, which could result either form higher labeling of the SR
protein or from relatively higher amounts of VDAC/mg total protein in the SR
membranes. [14C]Dicyclohexylcarbodiimide labeling of the SR, but not the
mitochondrial VDAC, was biphasic with respect to time and concentration of
[14C]dicyclohexylcarbodiimide. Partial digestion of [14C]dicyclohexylcarbodiimide
labeled SR-VDAC with chymotrypsin yielded five proteolytic fragments which were
recognized by the anti-VDAC Ig, and the dicyclohexylcarbodiimide-binding site was
localized in the 19-kDa fragment. VDAC was purified from SR and mitochondrial
membranes by spermine-agarose column. The interaction of dicyclohexylcarbodiimide
with functional carboxyl residue(s) in the purified VDAC is demonstrated by
recording its channel activity, following its reconstitution into planar lipid
bilayer (PLB). Dicyclohexylcarbodiimide inhibited the channel activity in a
voltage-dependent manner, requiring incubation with dicyclohexylcarbodiimide at
high (negative or positive) potentials. Dicyclohexylcarbodiimide slowed down the
transition from the high-conducting to a long-lived low-conducting states of the
channel (approximately 20% of its maximal conductance), by stabilizing the
intermediate states. Similar results were also obtained with purified
reconstituted mitochondrial VDAC. Hydrophilic carboxyl reagents [[1-ethyl-3-(3
dimethylamino)propyl] carbodiimide, N-ethyl-phenylisoxazolium-3'-sulfonate]
neither modified the channel activity nor prevented [14C]dicyclohexylcarbodiimide
labeling. These results indicate that dicyclohexylcarbodiimide interacts with a
carboxyl group located in a hydrophobic region of the protein which is involved
in the channel gating.
PMID- 9654060
TI - Inhibition of growth and aggregation of calcium oxalate crystals in vitro--a
comparison of four human proteins.
AB - The aim of this study was to compare directly, in the absence of interfering
contaminants, the inhibitory effects of Tamm-Horsfall glycoprotein (THG), human
serum albumin (HSA), alpha1-microglobulin and prothrombin fragment 1 (PTF1) on
calcium oxalate crystallization. These proteins have been detected in urinary
calculi, and with the exception of THG in calcium oxalate crystals generated from
undiluted human urine. THG was isolated from the urine of healthy men, while PTF1
was purified from Prothrombinex-HT, a human blood concentrate; HSA and alpha1
microglobulin were obtained from commercial sources. The effects of these
proteins were determined, separately, at the same final concentration (32 nM) on
calcium oxalate crystallization in a seeded, inorganic reaction system, using
Coulter Counter and [14C]oxalate analysis. Analysis of [14C]oxalate data showed
that THG, HSA and alpha1-microglobulin had no measurable effect on deposition of
calcium oxalate. However, PTF1 significantly inhibited mineral deposition by
19.6%. The average size of the particles precipitated was reduced from the
control value of 8.6 microm to 7.3, 5.9, 5.6 and 4.0 microm in the presence of
alpha1-microglobulin, HSA, THG and PTF1 respectively. These findings were
confirmed by scanning electron microscopy, which also revealed that the smaller
particles deposited in the presence of the proteins resulted from reduced crystal
aggregation rather than a decrease in the size of the individual crystals. It was
concluded that, on a molar basis, PTF1 is a more potent inhibitor of calcium
oxalate crystal aggregation than THG, HSA and alpha1-microglobulin. Moreover,
unlike those proteins it significantly inhibits the deposition of calcium
oxalate. These findings have implications for the putative role of urinary
proteins in the formation of calcium oxalate stones.
PMID- 9654061
TI - The formate dehydrogenase-cytochrome c553 complex from Desulfovibrio vulgaris
Hildenborough.
AB - The electron transfer between formate dehydrogenase and cytochrome c553 from the
anaerobic bacteria Desulfovibrio vulgaris Hildenborough has been investigated.
Parameters of the electron transfer kinetics are reported. The ionic strength
dependence of the complex formation has been evidenced. Two mutants of cytochrome
c553 have been obtained using site-directed mutagenesis with the substitutions
K62E and K62E,K63E. According to one-dimensional and two-dimensional NMR
analysis, the two variants were found to have the same folding pattern as that of
the wild-type cytochrome. The replacements of the lysine residues by acidic
groups have important effects on the affinity between the two oxidoreduction
partners. K62 and K63 are essential for recognition between the formate
dehydrogenase and the cytochrome c553. Previous structural studies of cytochrome
c553 have demonstrated the involvement of the polypeptide chain in the modulation
of the particular low oxidoreduction potential of this cytochrome. The present
study provides evidence that, during the evolution of cytochromes from the
anaerobic metabolism to aerobic respiration and photosynthesis, the electrostatic
distribution at the recognised encounter surface around the heme is highly
conserved in all cytochromes.
PMID- 9654062
TI - Pigment-binding properties of the recombinant photosystem II subunit CP26
reconstituted in vitro.
AB - CP26 is the most recently described antenna protein in higher plants which has
been reported to be involved in xanthophyll-dependent regulation of the light
harvesting function but is largely unknown due to the difficulties of
purification. In this study we have overexpressed in Escherichia coli the Lhcb5
gene product and reconstituted CP26 in vitro by refolding the recombinant protein
in the presence of chlorophyll a, chlorophyll b and xanthophylls. The resulting
pigment-protein complex is stable enough to be isolated by partially denaturing
gel electrophoresis. Reconstitution and isolation conditions for CP26 are similar
to those used for other chlorophyll a/b complexes like the major light-harvesting
complex of photosystem II (LHCII) and CP29; however, CP26 differs with regard to
its lower specificity in carotenoid binding. Most significantly, rather stable
recombinant CP26 can be reconstituted containing violaxanthin as the only
carotenoid. This enhanced plasticity with respect to carotenoid binding is
consistent with CP26 being the major binding protein of violaxanthin involved in
the xanthophyll cycle. The availability of recombinant CP26 opens the way to a
better characterisation of this pigment-protein complex with regard to its
biochemistry and its physiological functions.
PMID- 9654063
TI - Oxygen exchange with water in heme-oxo intermediates during H2O2-driven oxygen
incorporation in aromatic hydrocarbons catalyzed by microperoxidase-8.
AB - The present paper describes the oxygen incorporation into naphthalene and
anthracene by H2O2-driven microperoxidase-8, forming alpha-naphthol and
anthraquinone, respectively. Microperoxidase-8 is a minienzyme containing a
histidinyl-coordinated Fe3+-protoporphyrin IX cofactor covalently attached to an
eight-amino-acid peptide. Additional experiments were performed to investigate
whether the reaction mechanism involved is like that of peroxidase and/or
cytochrome P-450. A reaction pathway like that of cytochrome P-450 implies oxygen
transfer to the substrate from the as yet uncharacterized iron-oxo species formed
in the reaction of the heine cofactor with H2O2. In contrast, a peroxidase-type
reaction chemistry involves reaction pathways proceeding by initial one-electron
oxidation of, or H-abstraction from, the substrate, followed by incorporation of
oxygen from sources other than the iron-oxo species, i.e. from other than H2O2.
The results of the present study exclude Fenton-type chemistry and prove that the
minicatalyst is able to catalyze the oxygen incorporation by both peroxidase and
cytochrome P-450 types of reaction pathways, while exchange occurs between the
high-valency iron-oxo species and H2O. The mechanistic implications of this
exchange for cytochrome P-450 are discussed.
PMID- 9654064
TI - Kinetic analysis of integrin-dependent cell adhesion on vitronectin--the
inhibitory potential of plasminogen activator inhibitor-1 and RGD peptides.
AB - Distinct binding interactions between cell-surface receptors and extracellular
matrix components are characteristic of multifunctional adhesion proteins such as
vitronectin. The close proximity of binding sites for alpha(v)-integrins and
plasminogen activator inhibitor-1 (PAI-1) on vitronectin may have consequences
for cell adhesion and migration, or for the localized inhibition of plasminogen
activators. In this study, the kinetics and reversibility of vitronectin
dependent cell adhesion via alpha(v)-integrins was investigated using RGD
peptides and PAI-1 as competitors. Active, but not latent or cleaved PAI-1, and
RGD peptides were effective in preventing cell adhesion to vitronectin provided
the inhibitor was present at the time of cell seeding. In a concentration
dependent manner urokinase or thrombin abrogated the inhibitory effect of PAI-1.
Following cell seeding onto a vitronectin substratum, delayed addition of RGD
peptides or active PAI-1 (10-20 min post-seeding) resulted in the loss of their
inhibitory potential. These data were supported by experiments in a purified
system where delayed addition of active PAI-1 could no longer prevent vitronectin
binding to immobilized alpha(v)beta3, while a cyclic RGD peptide gave some
moderate inhibition. The apparent stabilization of vitronectin-integrin contacts
was observed with immobilized native or multimeric vitronectin but not with the
more rigid form of denatured, aggregated multimers. These results demonstrate
that the cell adhesive properties of vitronectin depend on its conformational
flexibility and can be tightly regulated in a spatio-temporal manner through
direct competition of cellular integrins by soluble or matrix-bound factors such
as PAI-1.
PMID- 9654065
TI - Cloning, purification and characterisation of the lipase from Staphylococcus
epidermidis--comparison of the substrate selectivity with those of other
microbial lipases.
AB - On the chromosome of Staphylococcus epidermidis RP62A the lipase gene (gehSE1) is
immediately flanked by the icaAA'BC operon, which is involved in biofilm
formation. Since lipase production might play a role in staphylococcal skin
colonisation as well, we studied the biochemical properties of the staphylococcal
lipases more closely. The DNA sequence and the deduced protein sequence revealed
that gehSE1 is very similar to the lipase sequence of S. epidermidis strain 9.
Like other staphylococcal lipases, gehSE1 is organised as a preproenzyme. The
part of gehSE1 coding for the mature lipase was cloned and overexpressed as a
fusion protein with an N-terminal histidine tag in Escherichia coli. The lipase
was purified to homogeneity using a combination of precipitation techniques,
metal-affinity chromatography and gel filtration. Biochemical characterisation
showed that this lipase is closely related to the lipase from Staphylococcus
aurelis NCTC8530. Both enzymes have a pH optimum around 6, are very stable at low
pH, and need calcium as a cofactor for catalytic activity. The preferred
substrates are small triacylglycerols, with a maximum activity toward
tributyrylglycerol. Comparison of the substrate selectivity with those of other
microbial lipases showed that phospholipids are generally poor substrates for
lipases. An exception is the lipase from Staphylococcus hyicus, which prefers
phospholipids as a substrate, distinguishing this staphylococcal lipase from
other microbial lipases. These results are discussed in view of the
structure/function relationships of staphylococcal lipases, and the possible
involvement of these enzymes in biological processes such as skin colonisation
and pathogenesis.
PMID- 9654066
TI - Sulfhydryl reagent susceptibility in proteins with high sequence similarity-
triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi and
Leishmania mexicana.
AB - The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei,
Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the
numbering system for the T. brucei enzyme, in their aligned sequences, the T.
cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and
126. T. brucei triosephosphate isomerase has cysteine residues at positions 14,
40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and
methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi
triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity
of wild type triosephosphate isomerase from T. cruzi and T. brucei to the
reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes,
respectively. Triosephosphate isomerases that have cysteine residues at positions
40 and 126, but lack a cysteine residue at position 14 are insensitive to
methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At
stoichiometric concentrations, the reagents inhibited the three enzymes as a
consequence of structural alterations as measured by binding of 8-anilino-1
napthalenesulfonic acid to previously buried hydrophobic regions. However, the
times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T.
cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The
effect of pH on the action of the sulfhydryl reagents and molecular modeling
showed no differences in the solvent accessibility of Cys14. As Cys14 forms part
of the dimer interface, the data indicate that, in the three enzymes, barriers of
different magnitude hinder the interaction between the sulfhydryl reagents and
Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its
dimer interface more susceptible for perturbation.
PMID- 9654067
TI - Purification and characterization of dimethylamine:5-hydroxybenzimidazolyl
cobamide methyltransferase from Methanosarcina barkeri Fusaro.
AB - Dimethylamine:5-hydroxybenzimidazolylcobamide methyltransferase (DMA-MT) was
purified from cells of Methanosarcina barkeri Fusaro grown on trimethylamine. In
the presence of methylcobalamine:coenzyme M methyltransferase isoenzyme II
[MT2(II)] the enzyme quite specifically catalyzed the stoichiometric conversion
of dimethylamine (apparent Km = 0.45 mM) and 2-mercaptoethane-sulfonate (coenzyme
M) to monomethylamine and methyl-coenzyme M. Monomethylamine was a competitive
inhibitor of the reaction (Ki = 4.5 mM). The apparent molecular mass of DMA-MT
was 100 kDa and the enzyme was found to be a dimer, composed of identical 50-kDa
subunits. A corrinoid content of 0.9 +/- 0.1 mol B12/mol holoenzyme was
calculated from HPLC analysis. The as-isolated methyltransferase was inactive,
but it could be reductively reactivated. Activation required the presence of
methyltransferase-activating protein, ATP and dimethylamine. Incubation with
these compounds resulted in the methylation of the corrinoid prosthetic group.
PMID- 9654068
TI - Methanol:coenzyme M methyltransferase from Methanosarcina barkeri--identification
of the active-site histidine in the corrinoid-harboring subunit MtaC by site
directed mutagenesis.
AB - The enzyme system catalyzing the formation of methyl-coenzyme M from methanol and
coenzyme M in Methanosarcina barkeri is composed of the three different
polypeptides MtaA, MtaB and MtaC of which MtaC harbors a corrinoid prosthetic
group. The heterologous expression of mtaA and mtaB in Escherichia coli has been
described previously. We report here on the overproduction of the apoprotein of
MtaC in E. coli, on its reconstitution to the active holoprotein with either
cob(II)alamin or methyl-cob(III)alamin, and on the properties of the
reconstituted corrinoid protein. Reconstituted MtaC was found to contain 1 mol
bound cobamide/mol. EPR spectroscopic evidence is presented for a His residue as
an axial ligand to Co2+ of the bound corrinoid. This active-site His was
identified by site-directed mutagenesis as His136 in the MtaC sequence that
contains four His residues. The reconstituted MtaC, in the cob(I)amide oxidation
state, was methylated with methanol in the presence of MtaB and demethylated with
coenzyme M in the presence of MtaA. In the presence of both MtaB and MtaA, methyl
coenzyme M was formed from methanol and coenzyme M at specific rates comparable
to those determined for the enzyme system purified from M. barkeri. M. barkeri
contains an isoenzyme of MtaA designated MtbA. The isoenzyme reacted with MtaC
with only 2.5% of the activity of MtaA.
PMID- 9654069
TI - O-demethylase from Acetobacterium dehalogenans--substrate specificity and
function of the participating proteins.
AB - The ether-cleaving O-demethylase isolated from syringate-grown cells of
Acetobacterium dehalogenans (formerly named strain MC) consists of four proteins,
components A, B, C and D. The enzyme system converts only phenyl methyl ethers
with a hydroxyl group in the ortho position to the methoxyl moiety. The presence
of a carboxyl group in the aromatic compound was not required for O-demethylase
reaction. Component B mediated the conversion of vanillate to 3,4
dihydroxybenzoate in the presence of the Ti(III)-reduced corrinoid-containing
component A. After addition of component D and tetrahydrofolate, methyl
tetrahydrofolate was formed from vanillate in stoichiometric amounts.
Titanium(III) citrate as a reductant could be replaced by H2, methyl viologen or
ferredoxin, partially purified hydrogenase, purified component C obtained from A.
dehalogenans, and ATP. From these findings, it was deduced that component B
serves as vanillate:corrinoid protein methyltransferase (methyltransferase I)
mediating the methyl transfer from vanillate to the reduced corrinoid protein
component A. Component D functions as methylcorrinoid protein:tetrahydrofolate
transferase (methyltransferase II). The role of component C is probably that of
an activating protein reversing accidental oxidation of the protein-bound
cob(I)alamin to cob(II)alamin in the presence of ATP and reducing equivalents
supplied by the enzymatic oxidation of hydrogen.
PMID- 9654070
TI - Kinetic mechanism of vanillyl-alcohol oxidase with short-chain 4-alkylphenols.
AB - The kinetic mechanism of vanillyl-alcohol oxidase with 4-methylphenol, 4
ethylphenol, 4-propylphenol and their C alpha-deuterated analogs has been studied
at pH 7.5 and 25 degrees C. Conversion of 4-methylphenol is extremely slow (0.005
s(-1)) while the enzyme is largely in the reduced form during turnover. 4
Ethylphenol and 4-propylphenol are readily converted while the enzyme is mainly
in the oxidized form during turnover. The deuterium kinetic isotope effect for
overall catalysis ranges between 7-10 whereas the intrinsic deuterium kinetic
isotope effect for flavin reduction ranges over 9-10. With all three 4
alkylphenols, flavin reduction appeared to be a reversible process with the rate
of reduction being in the same range as the rate for the reverse reaction. During
the reductive half-reaction of vanillyl-alcohol oxidase with 4-ethylphenol and 4
propylphenol, a transient intermediate is formed with an absorbance maximum at
330 nm. This intermediate has been tentatively identified as the p-quinone
methide of the aromatic substrate in complex with reduced enzyme. It is concluded
that vanillyl-alcohol oxidase catalysis with 4-ethylphenol and 4-propylphenol
favors an ordered sequential binding mechanism in which the rate of flavin
reduction determines the turnover rate while the reduced enzyme-p-quinone methide
binary complex rapidly reacts with dioxygen. During the reaction of vanillyl
alcohol oxidase with 4-methylphenol, a fluorescent enzyme species is stabilized.
Based on its spectal characteristics and crystallographic data [Mattevi, A.,
Fraaije, M. W., Mozzarelli, A., Olivi, L., Coda, A. & van Berkel, W. J. H. (1997)
Structure 5, 907-920], it is proposed that this species represents a covalent 5
(4'-hydroxybenzyl)-FAD adduct. With 4-ethylphenol and 4-propylphenol, similar N5
flavin adducts may be formed but their rate of formation is too slow to be of
catalytic relevance.
PMID- 9654071
TI - Structure and regulation of the bifunctional enzyme lysine-oxoglutarate reductase
saccharopine dehydrogenase in maize.
AB - The lysine-oxoglutarate reductase (LOR) domain of the bifunctional enzyme lysine
oxoglutarate reductase-saccharopine dehydrogenase (LOR/SDH) from maize endosperm
was shown to be activated by Ca2+, high salt concentration, organic solvents and
Mg2+. The Ca2+-dependent enhancement of LOR activity was inhibited by the
calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7)
and calmidazolium. Limited proteolysis was used to assess the structure/function
relationship of the enzyme. Digestion with elastase separated the bifunctional
125-kDa polypeptide into two polypeptides of 65 kDa and 57 kDa, containing the
functional domains of LOR and SDH, respectively. Proteolysis did not affect SDH
activity, while LOR showed a time-dependent and protease-concentration-dependent
inactivation followed by reactivation. Prolonged digestion or increasing amounts
of elastase produced a complex pattern of limit polypeptides derived from
additional cleavage sites within the 65-kDa (LOR) and 57-kDa (SDH) domains. The
SDH-containing polypeptides inhibited the enzymatic activity of LOR-containing
polypeptides. When separated from the SDH domain by limited proteolysis and ion
exchange chromatography, the LOR domain retained its Ca2+ activation property,
but was no longer activated by high salt concentrations. These results suggest
that the LOR activity of the native enzyme is normally inhibited such that after
modulation, the enzyme undergoes a conformational alteration to expose the
catalytic domain for substrate binding.
PMID- 9654072
TI - Structure and cross-reactivity of the O-specific polysaccharide of Proteus
penneri strain 26, another neutral Proteus O-antigen containing 2-acetamido-2,6
dideoxy-L-glucose (N-acetyl-L-quinovosamine).
AB - A neutral O-specific polysaccharide obtained from the lipopolysaccharide of
Proteus penneri strain 26 was studied using sugar analysis and 1H and 13C NMR
spectroscopy, including two-dimensional NMR techniques. The following structure
of the trisaccharide repeating unit was established: -->6)-alpha-D-GlcpNAc-(1-
>3)-alpha-L-QuipNAc-(1-->3)-alpha-D-Glcp NAc-(1--> where L-QuiNAc is 2-acetamido
2,6-dideoxy-L-glucose (N-acetyl-L-quinovosamine). Cross-reactivity of the Proteus
penneri 26 anti-O serum with other strains of P. penneri isolated in Poland and
USA and one strain of P. vulgaris is discussed.
PMID- 9654073
TI - The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with
nucleolar protein p120.
AB - Protein p120 is a proliferation-related nucleolar protein which is detectable
early in the G1 phase of the cell cycle and peaks early in the S phase. Most
human malignant tumors contain much higher levels of protein p120 than normal
resting cells. To identify p120-associated protein(s), a yeast two-hybrid screen
was carried out using protein p120 as the bait. Two positive clones encoded
portions of a novel protein, designated microspherule protein 58 kDa (MSP58).
MSP58 mRNA is 1.9 kb and encodes an approximately 58-kDa polypeptide of 462 amino
acids as shown by Western blotting of HeLa nucleolar proteins. The mouse MSP58
homolog has 97% amino acid similarity to human MSP58, but no MSP58 homolog was
found in the yeast genome. The MSP58 N-terminal region contains serine-rich
clusters and its C-terminal region has a coiled-coil domain. In insect Sf9 cells,
recombinant p120 and MSP58 proteins associated with each other, confirming the
results of the yeast two-hybrid assay. Deletion mutations revealed that the
binding of MSP58 to p120 required a previously unrecognized coiled-coil domain
within the N-terminal region of p120 and the C-terminal region of MSP58 protein.
Immunofluorescence indicated that the MSP58 protein is localized in
microspherules in the nucleolus. Anti-MSP58 Ig labeled nucleolar 'caps' when HeLa
cells were treated with actinomycin D. When the MSP58 protein was overexpressed
in COS-7 cells, the nucleolus became irregularly enlarged, which suggests that
MSP58 may affect the size and shape of the nucleolus.
PMID- 9654074
TI - Reductive metabolism of the hypoxia marker pimonidazole is regulated by oxygen
tension independent of the pyridine nucleotide redox state.
AB - 2-Nitroimidazoles, such as pimonidazole, are reduced in cells with low oxygen
tension and are, therefore, used as hypoxia markers. However, the effect of the
pyridine nucleotide redox state on pimonidazole reduction is not known.
Therefore, livers from fed or fasted rats were perfused with oxygen-saturated
buffer containing pimonidazole (400 microM) in the presence and absence of an
inhibitor of the mitochondrial respiratory chain, potassium cyanide; these
treatments were used to modulate the mitochondrial and cytosolic pyridine
nucleotide redox states. Pimonidazole-induced increases in oxygen uptake over
basal values were as follows: fed, 15.1 +/- 2.4; fasted, 4.2 +/- 0.8; fed + KCN,
32.1 +/- 0.9; fasted + KCN, 0.2 +/- 0.2 micromol x g(-1) x h(-1). However, if
NADPH was added in excess, microsomal oxygen uptake due to oxidative metabolism
of pimonidazole was independent of treatment. These results indicate that
pimonidazole-stimulated O2 uptake, due predominantly to N-oxidation and
glucuronidation, is dependent on the NADPH redox state. In contrast, reduced
pimonidazole adducts, detected immunochemically, accumulated in pericentral
regions in liver. Increasing the NADH redox state by inhibiting the mitochondrial
respiratory chain with KCN decreased protein-bound pimonidazole adducts.
Concomitantly, the average O2 tension of the liver was increased at least 30%.
However, KCN had no effect on total pimonidazole adducts detected by ELISA,
although both cytosolic (lactate/pyruvate) and mitochondrial (3
hydroxybutyrate/acetoacetate) NADH redox states were elevated by at least a
factor of eight. These results indicate that, unlike oxidative metabolism, the
pyridine nucleotide redox state does not determine the rate of reductive
metabolism of pimonidazole. Instead, the cellular oxygen tension regulates this
process. Therefore, even in cases where the supply of reducing equivalents is
increased (e.g., ethanol metabolism), accumulation of the reduced bound product
of pimonidazole is oxygen dependent in liver.
PMID- 9654075
TI - Engineering, expression and biochemical characterization of the hemoglobin domain
of a Erwinia chrysanthemi flavohemoprotein.
AB - An artificial hemoglobin-like domain has been constructed by engineering the gene
coding for the multi-domain flavohemoprotein from the bacterium Erwinia
chrysanthemi. This domain was designed by molecular modelling, cloned and over
expressed in Escherichia coli. The holo-protein was obtained in large quantities
after extraction from inclusion bodies and refolding in presence of alkaline
hemin. The purified 140-residue domain was studied and characterized to gain new
insights into the biochemical function of the recombinant domain and the
biological role of this new flavohemoprotein. The structural and functional
features of this domain in solution were studied using far-ultraviolet circular
dichroism, resonance Raman, proton-NMR spectroscopy, flash laser photolysis and
molecular modelling. The recombinant domain is shown to be folded properly and
active. This hemoglobin-like domain is able to bind oxygen and carbon monoxide
with very high affinity. It exhibits a rapid auto-oxidation which may explain its
tight association with a flavin containing reductase domain. A functional model
of this hemoglobin is discussed and compared with the X-ray structures of other
hemoproteins.
PMID- 9654076
TI - Photophysical properties of porphyrin planar aggregates in liposomes.
AB - This paper describes studies of some photophysical properties of non-covalent
planar aggregates of hematoporphyrin and protoporphyrin. This porphyrin species
has been recently discovered and can be generated in lipid bilayers such as
liposomes and inner mitochondrial membranes. The relative weight of this species
in different media, as compared to porphyrin monomers and stacked aggregates, has
been deduced by fluorescence decay studies. In contrast with what is observed for
stacked aggregates, promotion of planar suprastructures can occur both in aqueous
and lipid environments. The spectroscopic properties are very similar to those of
the corresponding monomers, in particular as regards the shape of the absorption
and emission spectra. The fluorescence decay times are generally higher than
those of the monomers, and depend on the medium in which the planar aggregates
are formed. The photooxidation properties of porphyrin planar aggregates, as
revealed by oxygen consumption and histidine photodegradation upon irradiation at
365 nm, were compared to those of the monomers. The extent of the photooxidation
process is nearly 20-30% higher in planar aggregates than in the monomers. In
contrast, it is well known that cofacial aggregates are photochemically inert and
only monomeric species of porphyrin are efficient photosensitizers. The
biological relevance of these findings is discussed.
PMID- 9654077
TI - Induction of necrosis by zinc in prostate carcinoma cells and identification of
proteins increased in association with this induction.
AB - Zinc exhibits inhibitory effects on apoptosis, and a deficiency in this metal
generally causes this type of cell death to occur. In the present study, we found
that exposure to zinc results in necrosis of prostate carcinoma cells. When zinc
acetate was added to LNCaP or PC-3 cells in monolayer culture, they began to
detach from the culture dishes, and viability was lost after 4-8 h. Most of the
cell death was found to be due to necrosis as determined by double staining with
fluorescein-isothiocyanate-labeled annexin V and ethidium bromide, and by
detection of hypodiploid cells. Associated with the induction of necrosis was an
increase in low molecular-mass proteins, identified by HPLC analysis to be
thymosin beta10, parathymosin and GAGE in LNCaP cells, and thymosin beta4,
parathymosin and metallothionein in PC-3. The time course of the increase of
thymosin beta10 in LNCaP cells and thymosin beta4 in PC-3 cells was consistent
with that of appearance of cell detachment and dead cells. These results indicate
that zinc can induce necrosis and suggest that production of proteins including
beta-thymosins is involved in induction of processes leading to cell detachment.
PMID- 9654078
TI - Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation
free hypoxia-inducible factor-1 DNA-binding site.
AB - The hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator involved in
the expression of oxygen-regulated genes such as that for erythropoietin.
Following exposure to low oxygen partial pressure (hypoxia), HIF-1 binds to an
hypoxia-response element located 3' to the erythropoietin gene and confers
activation of erythropoietin expression. The conserved core HIF-1 binding site
(HBS) of the erythropoietin 3' enhancer (CGTG) contains a CpG dinucleotide known
to be a potential target of cytosine methylation. We found that methylation of
the HBS abolishes HIF-1 DNA binding as well as hypoxic reporter gene activation,
suggesting that a methylation-free HBS is mandatory for HIF-1 function. The in
vivo methylation pattern of the erythropoietin 3' HBS in various human cell lines
and mouse organs was assessed by genomic Southern blotting using a methylation
sensitive restriction enzyme. Whereas this site was essentially methylation-free
in the erythropoietin-producing cell line Hep3B, a direct correlation between
erythropoietin protein expression and the degree of erythropoietin 3' HBS
methylation was found in different HepG2 sublines. However, the finding that this
site is partially methylation-free in human cell lines and mouse tissues that do
not express erythropoietin suggests that there might be a general selective
pressure to keep this site methylation-free, independent of erythropoietin
expression.
PMID- 9654079
TI - Transcriptional regulation of the non-specific cross-reacting antigen gene, a
member of the carcinoembryonic antigen gene family up-regulated in colorectal
carcinomas.
AB - Human non-specific cross-reacting antigen (NCA), a close relative of the tumor
marker human carcinoembryonic antigen (CEA), is also an in vitro homotypic
intercellular adhesion molecule capable of inhibiting differentiation when
expressed ectopically by myoblasts. Moreover, NCA appears to be overexpressed at
the transcriptional level to a greater extent and more frequently in colorectal
carcinomas than CEA. This study examines the transcriptional control mechanisms
responsible for orchestrating NCA expression. The region within 284 bp upstream
of the translational start site of the NCA gene was found to be capable of
directing high levels of expression in functional promoter assays. Footprinting
experiments identified three cis-acting elements and mobility-shift assays
revealed that the first of these elements is bound by the upstream stimulating
factors USF1 and USF2 while the other two are bound by the stimulatory proteins
Sp1 and Sp3. No cis-acting elements corresponding to CEA footprint FP4 or the
silencer CEA FP5 were detected in the NCA promoter, which may contribute to the
differential expression of NCA versus CEA in tumorigenesis.
PMID- 9654080
TI - DNA-binding properties of the tandem HMG boxes of high-mobility-group protein 1
(HMG1).
AB - High-mobility-group protein 1 (HMG1) is a conserved chromosomal protein with two
homologous DNA-binding HMG-box domains, A and B, linked by a short basic region
to an acidic carboxy-terminal tail. NMR spectroscopy on the free didomain (AB)
shows that the two HMG boxes do not interact. The didomain has a higher affinity
for all DNA substrates tested than single HMG-box domains and has a significantly
higher ability to distort DNA by bending and supercoiling. The interaction of the
didomain with DNA is stabilized by the presence of the basic region
(approximately 20 residues, 9 of which are Lys) that links the second HMG box to
the acidic tail in intact HMG1; this may be, at least in part, why this region
also enhances supercoiling of relaxed circular DNA by the didomain and
circularization of short DNA fragments (in the presence of ligase). Competition
assays suggest significantly different structure-specific preferences of single
and tandem HMG boxes for four-way junction and supercoiled plasmid DNA. Binding
to supercoiled DNA appears to be promoted by protein oligomerization, which is
pronounced for the didomains. Electron microscopy suggests that the oligomers are
globular aggregates, associated with DNA looping. One box versus two (or several)
is likely to be an important determinant of the properties of (non-sequence
specific) HMG-box proteins.
PMID- 9654081
TI - Cloning and characterization of a cDNA coding for Astacus embryonic astacin, a
member of the astacin family of metalloproteases from the crayfish Astacus
astacus.
AB - The astacin family of zinc endopeptidases was named after the digestive enzyme
astacin isolated from the crayfish Astacus astacus. Employing a reverse
transcription/PCR strategy with degenerate oligonucleotide primers specific for
two signature seqences of the astacin family, we have isolated a 1602-bp cDNA
from embryos of developing A. astacus eggs, which was designated Astacus
embryonic astacin (AEA). This cDNA was found to code for an astacin-like protease
domain which accounts for the N-terminal half of the predicted protein. The C
terminal half mainly consists of two complement subcomponent C1r/C1s/embryonic
sea urchin protein Uegf/bone morphogenetic protein 1 (CUB) domains. The
metalloprotease domain displays an amino acid sequence identity of 42% with
astacin. A higher sequence similarity was found to astacin family members that
act as hatching enzymes in different species, e.g. chorioallantoic membrane
protein 1 (CAM-1; from quail) and Xenopus hatching enzyme (formerly UVS.2), both
of which show 54% identity, and high and low choriolytic enzymes (HCE and LCE)
from the teleost Oryzias latipes (52% and 48% identity, respectively). A
relationship to astacin-like hatching enzymes is further supported by a
phylogenetic analysis of the protease domains. Expression of AEA mRNA in
developing embryos was found to be restricted to unhatched juveniles (larvae)
during the last 8 days before hatching. AEA transcripts could not be detected in
various tissues of adult animals or in eggs and embryos from an earlier
developmental stage. AEA expression starts about 8 days prior to hatching,
followed by a strong (18-fold) induction with a maximum at day 4 before hatching.
Newly hatched juveniles were found not to express the AEA mRNA.
PMID- 9654082
TI - Molecular cloning, expression and characterization of an Ascaris inhibitor for
pepsin and cathepsin E.
AB - Molecular cloning of a cDNA for a pepsin inhibitor in the round worm, Ascaris
suum, was achieved. The ORF was found to encode a 20-residue potential signal
peptide and a 149-residue inhibitor moiety. Northern analysis showed the mRNA for
the inhibitor to be expressed in the body wall and not in the viscera. To obtain
the active inhibitor, we constructed a yeast expression vector, pYES2API,
containing the inducible galactosidase promoter and a DNA fragment encoding a
fusion protein of the yeast alpha-factor leader and the Ascaris pepsin inhibitor.
The active inhibitor was secreted in the culture medium, the yield being
approximately 3 mg x l(-1) x day(-1), and purified by a two-step procedure that
included HPLC. The inhibitor inactivated pepsin A and cathepsin E almost
completely at amounts equimolar with the enzymes, but was 100-fold less effective
against pepsin C and did not act on cathepsin D and renin. Ki values for the
inhibition of pepsin A and cathepsin E were in the nanomolar range below pH 5.
Since the inhibitor activity was lost by modification of specific Lys residues,
including Lys110, an electrostatic interaction between these Lys residues and
Asp/Glu residues of pepsin A or cathepsin E was thought to be essential for the
inhibition.
PMID- 9654083
TI - Growth-blocking peptide expressed in the insect nervous system--cloning and
functional characterization.
AB - Growth-blocking peptide (GBP) is an insect biogenic peptide that retards larval
growth and, consequently, delays the onset of pupation of lepidopteran larvae.
Transcription of the GBP gene has been proven to be regulated in a tissue
dependent manner by an approximately 0.8-kb mRNA transcript in fat body and 2.5
kb transcript in the brain central nervous system (CNS) [Hayakawa, Y., Ohnishi,
A., Yamanaka, A., Izumi, S. & Tomino, S. (1995) FEBS Lett. 367, 185-189]. The GBP
cDNA in the brain CNS was isolated, sequenced and found to be almost identical
with that in the fat body, except that it encodes a long 5'-untranslated region
(approximately 1.1 kb), thus indicating that the brain CNS is synthesized as a
polyprotein precursor and released through posttranslational processing in the
same manner as that predicted in the fat body. Sequence analyses of the genomic
GBP gene fragments demonstrated that the 5'-untranslated region contains an
intron encoding a sequence element, TGATAA, which has been reported to be
important for expression in the insect larval fat body, suggesting that this
element contributes to a tissue-specific expression of the shorter GBP mRNA in
fat body. Ribonuclease protection assays showed that parasitization by a
parasitic wasp elevated the expression of GBP mRNA in brain CNS. The
parasitization-induced increase of GBP precursor and GBP concentrations was also
demonstrated in brain CNS. Brain CNS dopamine was increased eightfold by
incubating the tissue with GBP for 8 h through the elevation of dopa
decarboxylase activity by a transcriptional enhancement perhaps due to GBP
induced increase of cytoplasmic Ca2+ concentration. Dopamine elevation reduced in
vitro incorporation of methionine into proteins synthesized in brain CNS.
PMID- 9654084
TI - A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and
domain II of bikunin efficiently inhibits tumor cell invasion and metastasis.
AB - Urinary trypsin inhibitor (UTI) inhibits efficiently tumor cell invasion and the
formation of metastasis. The anti-metastatic effect is dependent on the COOH
terminal domain II of UTI [UTI-(78-136)-peptide]. To develop a molecule that
binds with high affinity to the urokinase (uPA) receptor (uPAR) on tumor cell
surfaces, a bifunctional hybrid molecule [uPA-(1-134)-UTI-(78-136)] consisting of
the uPAR-binding NH2-terminal fragment [UTI-(78-136)-peptide] of uPA at the NH2
terminus of UTI-(78-136)-peptide was produced in Escherichia coli by genetic
engineering. The purified hybrid protein inhibited trypsin and plasmin 2-3-fold
less effectively than UTI-(78-136)-peptide and was found to bind to human tumor
cells via uPAR, which was confirmed by cell binding and competition experiments.
Using a modified Boyden chamber and an artificial basement membrane, Matrigel, it
was found that the hybrid protein is very effective at inhibiting invasion by
uPAR-expressing human tumor cells. Sensitivities of tumor cells towards the anti
invasive effect of uPA-(1-134)-UTI-(78-136) correlated with the density of uPAR
on human tumor cells. Furthermore, in the spontaneous metastasis model, the
hybrid protein inhibited the formation of lung and/or lymphatic metastasis by
human ovarian carcinoma and choriocarcinoma cells. The hybrid protein was much
more effective than uPA-(1-134)-peptide, UTI-(78-136)-peptide, or UTI. We
conclude that this approach extends the possibility of applying recombinant
protein for therapeutic use in inhibition of human tumor cell metastasis.
PMID- 9654085
TI - Phosphatidylinositol 4-kinases.
AB - Polyphosphoinositides are involved in many signal transduction pathways in
eukaryotic cells. The first committed step is catalysed by phosphatidylinositol 4
kinase leading to the formation of phosphatidylinositol 4-phosphate. In the last
four years, ten cDNA molecules have been cloned which code isoforms of
phosphatidylinositol 4-kinase; some of which are highly related.
Characteristically, they contain a C-terminal catalytic domain which is similar
to that of (poly)phosphoinositide 3-kinases and to that of more distantly related
lipid/protein kinases. Alignment has characterised cDNAs from Chaenorabditis,
Dictyostelium and Schizostaphyloccus pombe as those of phosphatidylinositol 4
kinases also. All these lipid kinases are related to the superfamily of protein
kinases. Several amino acids are highly conserved in catalytic domains of lipid
and protein kinases. Employing the catalytic subunit of the cAMP-dependent
protein kinase as template, these residues can be assigned functionally. On the
basis of the alignment, a phylogenetic tree of the superfamily of
phosphatidylinositol kinases has been constructed. Three families, the
phosphatidylinositol 4-kinases, phosphoinositide 3-kinases, and the
phosphatidylinositol related lipid/protein kinases, can be recognised. Each
family comprises two subfamilies. The involvement of the phosphatidylinositol 4
kinases in signal transduction processes is summarised and a new hypothesis for
the function of their isoforms in polyphosphoinositide signalling is presented.
The involvement of phosphatidylinositol 4-kinases in formation of lipid-protein
interactions with cytoskeleton proteins and the metabolism of
polyphosphoinositide in the nucleus is discussed.
PMID- 9654086
TI - Monitoring of RNA polymerase-DNA UP element interaction by a fluorescent probe
conjugated to alpha subunit.
AB - The carboxy-terminal domain (CTD) of Escherichia coli RNA polymerase alpha
subunit was specifically modified by a reporter label, fluorescein mercuric
acetate (FMMA), conjugated to Cys269 on the surface of UP element recognition
helix. The modified enzyme was used to investigate RNA polymerase interaction
with different promoters, either with or without an UP element. In a single-round
transcription assay, the activity of modified RNA polymerase was found to
decrease as measured with rrnBP1, trpP and lacP2 promoters but not with many
other promoters including mutant rrnBP1 without the UP element, supporting the
idea that Cys269 or the domain including Cys269 is involved in UP element
recognition. Both trpP and lacP2 have sequence similarity to the rrnBP1 UP
element. The chemical modification of RNA polymerase, however, did not affect an
apparent equilibrium dissociation constant with rrnBP1, as measured by gel
retardation assays, indicating that the DNA-binding ability is retained even
after FMMA conjugation. Interaction with the rrnBP1 UP element led to substantial
alterations in the spectral parameters of the reporter label, which are different
from those induced by complex formation with promoters without UP elements. A
pronounced spectral blue shift suggests that the labeled surface of alphaCTD
closely approaches the charged UP DNA helix. These observations imply that the
fluorescent labeling at Cys269 can be used as a good tool for monitoring the
presence or absence of an UP element in a given promoter. Spectral parameters of
the label displayed the spectral blue shift when the modified RNA polymerase
interacted with trpP, supporting the prediction that this promoter carries an
rrnBP1-type UP element.
PMID- 9654087
TI - Tyrosine phosphorylation of the muscle-specific kinase is exclusively induced by
acetylcholine receptor-aggregating agrin fragments.
AB - During formation of the neuromuscular junction, the basal membrane protein agrin
initiates the aggregation of acetylcholine receptors (AChR) on the surface of
myotubes. A muscle-specific kinase (MuSK) becomes phosphorylated upon incubation
with agrin, although it does not bind to agrin on its own. Utilizing MuSK
specific antibodies, we demonstrate that the ability of different splicing
variants and truncation fragments of agrin to trigger MuSK phosphorylation and
AChR aggregation are correlated. Only agrin forms which are potent inducers of
AChR-clustering are able to trigger the phosphorylation of MuSK. Picomolar
concentrations of agrin are already sufficient to induce MuSK phosphorylation.
Similar amounts are necessary for the aggregation of AChRs as well as their
phosphorylation on a tyrosine residue. The complete overlap of specificities for
MuSK phosphorylation and AChR aggregation suggests that only binding of agrin to
a MuSK-containing receptor complex is responsible for the initiation of AChR
aggregation. In contrast, interactions of agrin with binding proteins on the
muscle surface harbouring different specificities such as alpha-dystroglycan do
not seem to be necessary for this process.
PMID- 9654088
TI - Different forms of the mRNA encoding the heat-shock transcription factor are
expressed during the life cycle of the parasitic helminth Schistosoma mansoni.
AB - Several cDNAs and a gene encoding the heat-shock transcription factor (HSF) of
schistosome were cloned, and multiple forms of the mRNA were found at different
developmental stages of the parasite. The encoded protein contained a DNA-binding
domain with expected sequence identity (39-58%) to other HSF molecules, and two
leucine zipper motifs (LZ123 and LZ4) involved in the oligomerization of HSF.
Adult worms express three isoforms of HSF mRNA generated by alternative splicing
inside the coding region that contains in-frame splice signals. Introns are not
involved in the process since the deleted segments (36 bp or 45 bp) are not
flanked by any intron in the gene. Structural variations generated by alternative
splicing (insertion of 3 amino acids or 15 amino acids) are continual with LZ4
and added hydrophobic residues are in register with the hydrophobic heptad
repeats of LZ4. Structural diversity at the C-terminus of LZ4 may affect the
strength of LZ4 interaction with the oligomerization domain (LZ123) and thus
modulate the DNA-binding activity of HSF. The conservation of this mechanism in
mouse and schistosome may reflect evolutionary pressure to generate multiple HSF
species exhibiting functional diversity and capable of responding to different
stress signals and physiological signals. Adult worms express HSF mRNA of 2.5 kb,
in agreement with the size of the cDNA, while cercariae (developmental stage
preceding adult worm) show multiple bands in the range 2.5-3 kb. Available data
indicate that the HSF mRNAs of cercariae are inactive. We propose that these mRNA
species are generated by an alternative splicing that incorporates introns, which
inactivate the mRNA by the insertion of termination codons and/or by shifting of
the reading frame. Parasite HSF protein produced in bacteria showed DNA sequence
recognition similar to that of HSF in parasite extracts, i.e. the recombinant HSF
reacted better with a variant heat-shock element (HSE; one base change in the
third NGAAN pentamer of the ideal HSE consensus sequence) than with the ideal
HSE. The size of the HSF gene is 12 kb and it is composed of ten exons and nine
introns. Excluding the introns, the gene and cDNA show 100% sequence identity. A
plant HSF gene contains only a single intron, which matches with the position of
intron I2 of schistosome. That the position of this intron is conserved in remote
species is indicative of an important function during evolution of the HSF gene.
PMID- 9654089
TI - Molecular cloning and characterization of mouse caspase-8.
AB - Fas (APO-1/CD95) is a transmembrane receptor protein which induces apoptosis upon
activation. In apoptosis triggered by Fas, a subset of cysteine proteases
designated caspases is activated, playing a central role as effector molecules.
Among these caspases, human caspase-8 (FLICE/MACH/Mch5) has been isolated and
shown to be indispensable for Fas-mediated apoptotic signaling. In this study, we
isolated the mouse homologue to human caspase-8 from a BaF3 cell cDNA library.
This molecule conserved the death effector domain (DED) and protease domain as
detected in human caspase-8, and was capable of inducing apoptosis in KB and Rat
1 cells when overexpressed. Expression of caspase-8 was detected in the various
tissues of adult mouse and in embryos at 9.5 days and 17.5 days of development by
Northern-blot analysis. Further, we isolated a chromosomal gene for caspase-8
from a mouse genomic library and analyzed the genomic structure of the isolated
gene. This gene consisted of eight exons and seven introns spanning about 26 kb
in the coding region.
PMID- 9654090
TI - Studies on the conformational changes in the bacterial cell wall biosynthetic
enzyme UDP-N-acetylglucosamine enolpyruvyltransferase (MurA).
AB - The enzyme UDP-N-acetylglucosamine (UDP-GlcNAc) enolpyruvyltransferase (MurA),
the target of the antibiotic fosfomycin, was investigated by small-angle X-ray
scattering (SAXS) and fluorescence spectroscopy to detect conformational changes
that had been proposed on the basis of the crystal structure of unliganded and
liganded MurA. The SAXS data indicate that binding of UDP-GlcNAc to free enzyme
results in substantial conformational changes, which can be interpreted as the
transition from an open to a closed form. Fosfomycin did not affect the structure
of free enzyme or sugar-nucleotide-bound MurA. Phosphoenolpyruvate (pyruvate-P)
appeared to induce a structural change upon addition to free enzyme, which
differed from that observed upon binding of UDP-GlcNAc. Fluorescence experiments
were performed using the hydrophobic fluorescence probe 8-anilino-1-naphthalene
sulfonate (ANS). The fluorescence quenching of MurA/ANS solutions upon addition
of UDP-GlcNAc or pyruvate-P was concentration dependent in a saturating manner,
yielding apparent dissociation constants of K(d(UDP-GlCNAc)) = 59 microM and
K(d(pyruvate-P)) = 240 microM. The results suggest that binding of substrates
does not exclusively follow an ordered mechanism with UDP-GlcNAc binding first,
although binding of UDP-GlcNAc to free enzyme is preferred and possibly
influenced by pyruvate-P. The reaction thus appears to follow an induced-fit
mechanism, in which the binding site for fosfomycin, and presumably also for
pyruvate-P, is created by the interaction of free enzyme with the sugar
nucleotide. The methods described here provide a tool for the characterization of
site-directed mutants of MurA and the interaction of this enzyme with potential
inhibitors.
PMID- 9654091
TI - Effect of single mutations on the structural dynamics of a DNA repair enzyme, the
Escherichia coli formamidopyrimidine-DNA glycosylase--a fluorescence study using
tryptophan residues as reporter groups.
AB - The effects on the structure dynamics of the Escherichia coli wild-type
formamidopyrimidine-DNA glycosylase (Fpg) protein of the single mutations Lys57-
>Gly (FpgK57G), Pro2-->Gly (FpgP2G) and Pro2-->Glu (FpgP2E) were studied by
fluorescence techniques, namely: lifetime measurements and acrylamide quenching
of the fluorescence of Trp residues. The fluorescence decays of Fpg and its
mutant forms were analysed by the maximum-entropy method and lifetime
distributions in the range 200 ps to 9 ns were obtained. The lifetime
distribution profiles of FpgK57G, FpgP2G and FpgP2E are different from that of
wild-type Fpg. Both dynamic and static quenching by acrylamide were observed for
all the proteins. At 20 degrees C, the bimolecular collisional quenching rate
constant of the FpgP2E fluorescence by acrylamide was only 0.8 M(-1) s(-1) as
compared to about 1.4 M(-1) s(-1) for the three other proteins. At 6 degrees C,
all the spectroscopic properties of these four proteins are about the same. The
analysis of experimental data demonstrates that all three mutations induce a
structural reorganization of the Fpg protein. However, only the P2E mutation lead
to a reduced accessibility of some Trp residues to acrylamide quenching. It is
concluded that the single P2E replacement induces a conformational change leading
to a more rigid globular structure as opposed to the wild type and K57G and P2G
mutations. The influence of the single mutations on the enzyme activities of the
Fpg protein is discussed.
PMID- 9654092
TI - Downstream targets of urokinase-type plasminogen-activator-mediated signal
transduction.
AB - We have investigated cellular signalling events induced by urokinase-type
plasminogen activator (uPA) independent of its proteolytic activity. Treatment of
the human fibrosarcoma cell line HT 1080 with diisopropylphosphorofluoridate
inactivated uPA (Dip-F-uPA) triggers a cascade of intracellular signals which are
mediated by the specific cell surface receptor for uPA (uPAR). We have found that
anti-uPAR Ig precipitate the src-type protein tyrosine kinases fyn, hck and lck,
which belong to a family of structurally and functionally related effectors
participating in signalling from antigen and cytokine receptors. Of the three
uPAR-associated kinases, only hck is activated by uPA, whereas no changes in the
activities of either fyn or lck could be detected by an in vitro immune complex
kinase assay. We identified p38 and extracellular-signal-regulated kinase 2 from
the mitogen-activated protein kinase family as downstream components of a set of
consecutive signalling molecules which teleologically alter the program of gene
expression. Exposure of cells to uPA results in a significant increase in c-fos
mRNA that is partially due to an elevated rate of gene transcription. Presumably,
the activation of the c-fos gene leads to the subsequent formation of the
transcription factor activator protein-1 (AP-1), since accumulation of c-fos mRNA
is followed by induction of target genes sensitive to AP-1 such as plasminogen
activator inhibitor type 2 (PAI-2). These results provide new insights into
proteolysis-independent cytokine-like effects of uPA.
PMID- 9654093
TI - Expression of fatty-acid-binding proteins in cells involved in lung-specific
lipid metabolism.
AB - Members of the fatty-acid-binding protein (FABP) family are thought to play an
important role in fatty acid transport within the cytosol and thus to be involved
in lipid metabolism. As previous data on the occurrence of distinct FABP types in
total lung are contradictory, we determined the expression of FABP types in three
isolated cell types of rat lung, which are characterised by active lipid
metabolism. Alveolar type-II cells synthesise, store and secrete pulmonary
surfactant, a phospholipid-rich surface-tension-lowering agent, whereas lung
fibroblasts, localised adjacent to the alveolar type-II cells, are assumed to
provide neutral lipid substrate to alveolar type-II cells around birth, and
alveolar macrophages are known to degrade complex lipids. Initial screening by
reverse transcriptase PCR revealed the occurrence of heart (H-), epidermal (E-)
and liver FABP in rat lung, the latter being not detectable in the three cell
types studied. Cells were analysed by northern and western blotting, then
quantitatively by sandwich ELISA, for which recombinant rat E-FABP was prepared.
E-FABP mRNA was found in all three cell types, and E-FABP was detected in the
following amounts: 240.9 +/- 19.0 ng/mg cytosolic protein in alveolar type-II
cells; 172.3 +/- 0.7 ng/mg protein for lung fibroblasts; and 36.9 +/- 3.5 ng/mg
protein for alveolar macrophages. This indicates a basic function of E-FABP in
cellular lipid metabolism. In contrast, H-FABP probably is involved in the
metabolism of neutral lipids because H-FABP mRNA was found only in lung
fibroblasts with a corresponding protein level of 315.5 +/- 6.9 ng/mg. Small
amounts of H-FABP protein were present in alveolar type-II cells and alveolar
macrophages.
PMID- 9654094
TI - The reductase RedA2 of the multi-component dioxin dioxygenase system of
Sphingomonas sp. RW1 is related to class-I cytochrome P450-type reductases.
AB - The first step in the oxidation of the diaryl ethers dibenzo-p-dioxin and
dibenzofuran by the bacterium Sphingomonas sp. RW1 is carried out by an atypical
multi-component ring hydroxylating dioxygenase. This heteromeric enzyme requires
the participation of a flavoprotein, reductase A2, and an iron-sulfur protein,
Fdx1, to mediate the transfer of electrons from NADH to the dioxygenase for
oxygen activation [Bunz, P. V. & Cook, A. M. (1993) J. Bacteriol. 175, 6467
6475]. From the type of ferredoxin (Fd) and flavoprotein, this complex is
presumed to belong to the class-IIA dioxygenase system which has not been
genetically analysed so far. The gene encoding the flavoprotein was identified by
screening a genomic library constructed in pLAFR3 with a probe generated by PCR
amplification. The nucleotide sequence of a 2.0-kb DNA fragment encompassing the
reductase gene, redA2, was determined. The specified protein shares 37-40%
identity with class-I cytochrome P450 reductases and 27-35% identity with
reductases acting with class-IIB dioxygenases. An FAD-binding amino acid
consensus sequence, as well as an NADH-binding site were detected by analogy
beginning at residues 10 and 153, respectively. The redA2 gene is not linked to
the dioxin dioxygenase cistrons. The rare start codon, GTG, of the reductase was
changed to ATG and the modified gene hyperexpressed in Escherichia coli using the
strong T7 polymerase promoter. The recombinant reductase was purified to
homogeneity with an approximate yield of 3.3 mg/g wet mass cells. Flavin analysis
confirmed the presence of 1 FAD/mol protein. The Km values for NADH and Fdx1 are
22 (+/- 3) microM and 3.7 (+/- 0.4) microM, respectively.
PMID- 9654095
TI - Molecular cloning and characterization of tomato cDNAs encoding glutathione
peroxidase-like proteins.
AB - In Lycopersicon esculentum, two cDNAs encoding glutathione peroxidase (GPX)-like
proteins were isolated, sequenced and characterized as putative phospholipid
hydroperoxide:glutathione peroxidases. After mechanical stimulation (rubbing) of
the plant, each GPX tomato gene was found to behave differently in terms of
inducibility and tissue distribution. The accumulation of GPX transcripts
suggests that reactive oxygen species are involved in the plant response to a
mechanical stress.
PMID- 9654096
TI - Bactericidal activity of Lys49 and Asp49 myotoxic phospholipases A2 from Bothrops
asper snake venom--synthetic Lys49 myotoxin II-(115-129)-peptide identifies its
bactericidal region.
AB - Mammalian group-II phospholipases A2 (PLA2) of inflammatory fluids display
bactericidal properties, which are dependent on their enzymatic activity. This
study shows that myotoxins II (Lys49) and III (Asp49), two group-II PLA2 isoforms
from the venom of Bothrops asper, are lethal to a broad spectrum of bacteria.
Since the catalytically inactive Lys49 myotoxin II isoform has similar
bactericidal effects to its catalytically active Asp49 counterpart, a
bactericidal mechanism that is independent of an intrinsic PLA2 activity is
demonstrated. Moreover, a synthetic 13-residue peptide of myotoxin II, comprising
residues 115-129 (common numbering system) near the C-terminal loop, reproduced
the bactericidal effect of the intact protein. Following exposure to the peptide
or the protein, accelerated uptake of the hydrophobic probe N-phenyl-N
naphthylamine was observed in susceptible but not in resistant bacteria,
indicating that the lethal effect was initiated on the bacterial membrane. The
outer membrane, isolated lipopolysaccharide (LPS), and lipid A of susceptible
bacteria showed higher binding to the myotoxin II-(115-129)-peptide than the
corresponding moieties of resistant strains. Bacterial LPS chimeras indicated
that LPS is a relevant target for myotoxin II-(115-129)-peptide. When
heterologous LPS of the resistant strain was present in the context of
susceptible bacteria, the chimera became resistant, and vice versa. Myotoxin II
represents a group-II PLA2 with a direct bactericidal effect that is independent
of an intrinsic enzymatic activity, but adscribed to the presence of a short
cluster of basic/hydrophobic amino acids near its C-terminal loop.
PMID- 9654097
TI - Thermodynamic stability of two variants of xylanase (Xys1) from Streptomyces
halstedii JM8.
AB - In a continuation of our earlier study [Ruiz-Arribas, A., Santamaria, R.I.,
Zhadan, G. G., Villar, E. & Shnyrov, V. L. (1994) Differential scanning
calorimetric study of the thermal stability of xylanase from Streptomyces
halstedii JM8, Biochemistry 33, 13787-13791], we used high-sensitivity
differential scanning microcalorimetry, intrinsic tryptophan fluorescence and far
ultraviolet circular dichroism to study the effect of regional sequence
differences on the thermodynamic stability of xylanase (Xys1) from Streptomyces
halstedii JM8 (1,4-beta-D-xylanohydrolase, EC 3.2.1.8). Thermal transitions were
measured for original xylanase (Xys1S) and two variants. Thermal denaturation of
all the xylanases studied revealed two structural domains, each of which, despite
its partial irreversibility, follows a two-state thermal unfolding process under
our experimental conditions. Both variants were found to exhibit slightly
decreased stability, possessing the same activity as the original. The unfolding
parameters for each domain of both variants, unlike the situation with wild-type
xylanase (see our previous report), fit some correlations obtained for the most
compact globular proteins. The values of enthalpy and entropy of
unfolding/residue at 383 K were found to be inversely proportional to residual,
well-regulated structures in unfolded states.
PMID- 9654098
TI - The initial kinetics of hydrolysis by cellobiohydrolases I and II is consistent
with a cellulose surface-erosion model.
AB - Introduction of a novel method for the quantification of the cellobiose released
made it possible to follow the initial stage of hydrolysis of bacterial
microcrystalline cellulose (BMCC) by cellobiohydrolases 1,4-beta-D-glucan
cellobiohydrolase I (CBH I) and 1,4-beta-D-glucan-cellobiohydrolase II (CBH II)
from Trichoderma reesei. A drastic retardation of the rate of the hydrolysis was
observed already at a very low degree of conversion. Earlier-suggested
retardation factors, such as product inhibition by cellobiose or enzyme
inactivation, could be discounted as primary causes for the pattern. A model
including steric hindrance by non-productive binding and erosion of the cellulose
surface during the processive action of exoenzymes was proposed to describe the
rate retardation observed. Simultaneous action of CBH I and CBH II on cellulose
was not a prerequisite for synergy between them.
PMID- 9654099
TI - Effect of mutations of residue 340 in the large subunit polypeptide of Rubisco
from Anacystis nidulans.
AB - Residues 338-342 at the C-terminal end of loop 6 in the large subunit beta/alpha
barrel structure of Rubisco influence specificity towards CO2 and O2. In
Anacystis nidulans Rubisco, replacement of alanine 340 by tyrosine or histidine
increased the specificity factor by 12-13%, accompanied by a 25-33% fall in Vc,
the rate of carboxylation, while replacement by asparagine increased the
specificity factor by 9% and Vc by 19%. Other mutations did not significantly
alter specificity. Alanine 340 does not interact directly with the bisphosphate
substrate, thus replacing it with other residues must have indirect effects on
the specificity factor and rate of carboxylation.
PMID- 9654100
TI - Pyrrole-2-carboxylate decarboxylase from Bacillus megaterium PYR2910, an organic
acid-requiring enzyme.
AB - Inducible pyrrole-2-carboxylate decarboxylase, which catalyzes the
decarboxylation of pyrrole-2-carboxylate to pyrrole and CO2 in stoichiometric
amounts, was purified from Bacillus megaterium PYR2910. The purity of the enzyme
was shown by SDS/PAGE and gel-permeation HLPC. The enzyme has a molecular mass of
approximately 98 kDa and consists of two identical subunits. It is highly
specific for pyrrole-2-carboxylate, and also catalyzes the reverse reaction, the
carboxylation of pyrrole. A unique feature of this enzyme is its requirement of
an organic acid, such as acetate, propionate, butyrate or pimelate. A possible
catalytic mechanism including a cofactor function of organic acid is discussed.
PMID- 9654101
TI - Structural characterisation of N-linked and O-linked oligosaccharides derived
from interferon-alpha2b and interferon-alpha14c produced by Sendai-virus-induced
human peripheral blood leukocytes.
AB - We have previously isolated and partially characterised the components of a
highly purified interferon-alpha (IFN-alpha) preparation produced by Sendai-virus
induced human peripheral blood leukocytes. Nine IFN-alpha species were
identified, and two of these were found to be glycosylated [Nyman, T. A., Tolo,
H., Parkkinen, J. & Kalkkinen, N. (1998) Identification of nine interferon-alpha
subtypes produced by Sendai-virus-induced human peripheral blood leukocytes,
Biochem. J. 329, 295-302]. Here, we isolated the N-linked oligosaccharides of IFN
alpha14c and the O-linked chains of IFN-alpha2b, and the glycans were
characterised by electrospray tandem mass spectrometry and by specific
glycosidase digestions monitored by matrix-assisted laser desorption ionisation
time of flight mass spectrometry. The IFN-alpha14c N-glycans were shown to
exhibit core-fucosylated biantennary glycans, with about 10% carrying an
additional alpha1,3-linked fucose unit at the antennae. The IFN-alpha2b was shown
to carry about 50% core type-1 disialyltetrasaccharides, 30% core type-1
monosialyltrisaccharides and 20% core type-2 monosialylpentasaccharides.
PMID- 9654102
TI - Mutant analysis reveals an alternative pathway for N-linked glycosylation in
Drosophila melanogaster.
AB - The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1),
and flies homozygous for small deletions of the gene are viable. They show but
few abnormalities and those have a low penetrance [Kerscher, S., Albert, S.,
Wucherpfennig, D., Heisenberg, M. & Schneuwly, S. (1995) Dev. Biol. 168, 613
626]. Here we sequence the N-linked oligosaccharides associated with a reporter
protein, and with membrane proteins prepared from wild type and MAS-1 null
organisms. The results show that the null organisms synthesise the same range of
oligosaccharides as wild type, albeit with different ratios. There is an
accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1
enzyme. This supports the suggestion of Kerscher et al. that the lack of severe
phenotypic disturbances in the null organisms is due to the presence of an
alternative pathway(s), but it also shows that this alternative pathway(s) does
not entirely compensate for the normal pathway.
PMID- 9654103
TI - Oligosaccharides derived by endo-beta-galactosidase digestion of bovine corneal
keratan sulphate--characterisation of tetrasaccharides with incomplete sulphation
and containing unsulphated N-acetylglucosamine residues.
AB - Bovine corneal keratan sulphate has been fragmented using the enzyme endo-beta)
galactosidase and 1H-NMR chemical shift data are reported for five newly isolated
tetrasaccharides which derived from the repeat region. They have the structures:
GlcNAc(beta1-3)Gal(beta1-4)GlcNAc6S(beta1-3)Gal-ol, GlcNAc6S(beta1-3)Gal(beta1
4)GlcNAc(beta1-3)Gal-ol, GlcNAc(beta1-3)Gal6S(beta1-4)GlcNAc6S(beta1-3)Gal-ol,
GlcNAc6S(beta1-3)Gal6S(beta1-4)GlcNAc(beta1-3)Gal-ol, and GlcNAc6S(beta1
3)Gal(beta1-4)GlcNAc6S(beta1-3)Gal-ol. Structures for two trisaccharides formed
by a peeling reaction are also given. These are GlcNAc(beta1-3)Gal6S(beta1
4)GlcNAc-ol and GlcNAc6S(beta1-3)Gal(beta1-4)GlcNAc6S-ol where GlcNAc6S-ol
represents N-acetylglucosaminitol 6-O-sulphate. Characterisation of such
structures and their spectral assignments will be of considerable value for the
studies of both selectin ligands and undersulphated keratan sulphates such as
those occurring on cell surfaces and in brain tissue.
PMID- 9654104
TI - Structural analysis of the phase-variable lipooligosaccharide from Haemophilus
somnus strain 738.
AB - The structure of the phase variable lipooligosaccharide (LOS) from Haemophilus
somnus strain 738 was elucidated. The LOS was subjected to a variety of
degradative procedures. The structures of the purified products were established
by monosaccharide and methylation analyses, NMR spectroscopy and mass
spectrometry. The following structures for the two major components were
determined on the basis of the combined data from these experiments. [structure
in text]. In the structures Kdo is 3-deoxy-D-manno-octulosonic acid, PEtn is
phosphoethanolamine, PCho is phosphocholine, Hep is L-glycero-D-manno-heptose,
and the remaining glucose units have the D configuration. The elucidation of
these structures has increased our understanding of the relationship between the
phase-variable LOS and the pathogenic potential of this organism.
PMID- 9654105
TI - Rules for the addition of O-linked N-acetylglucosamine to secreted proteins in
Dictyostelium discoideum--in vivo studies on glycosylation of mucin MUC1 and MUC2
repeats.
AB - One class of O-glycosylation in the simple eukaryote Dictyostelium discoideum
involves the addition of a single N-acetylglucosamine residue to Ser and Thr
residues on secreted or membrane-bound proteins at an early stage of development.
A previously developed in vivo approach for the identification of acceptor sites
for O-glycosylation was used to further characterise the specificity of the UDP
GlcNAc :polypeptide N-acetylglucosaminyltransferase(s). Glutathione S-transferase
fusion proteins were constructed to express and secrete the mucin peptide repeat
for MUC1 (PDT1RPAPGS1T2APPAHGVT3S2A) and a MUC2-like peptide
(PT1T2T3PIT4T5T6T7T8T9VT10PT11PT12PT13GT14QT15), respectively (superscript
numbers indicate residues with the potential to be glycosylated). Monosaccharide
analysis, electrospray-ionisation mass spectrometry and protein sequencing showed
that the modification is a single N-acetylglucosamine attached to certain Thr
residues. The MUC1 repeat was glycosylated on T2 and T3 and there were no
modifications on T1 or on S1 and S2. The MUC2 glycopeptide was glycosylated on
T1, T3, T5, T7, T9, T10, T11, T12, T13 and T14. Our results show that the D.
discoideum glycosylation apparatus incorporates GlcNAc residues into peptide
sequences similar to those reported for the addition of GalNAc residues in
mammalian tissues. The anomeric linkage of the GlcNAc residues to the polypeptide
chain was shown to be in alpha configuration as determined by NMR studies.
PMID- 9654106
TI - Several weak signals in the cytosolic and transmembrane domains of the
interleukin-2-receptor beta chain allow for its efficient endocytosis.
AB - Plasma membrane receptors are retrieved continually from the cell surface by
endocytosis and transported to intracellular organelles. They are internalized at
various rates depending on their ability to interact with endocytic structures of
the plasma membrane. The interleukin-2-receptor beta chain is endocytosed
constitutively and efficiently. Here we show that different motifs in its
cytosolic tail promote entry in an additive way, each of them acting as a weak
internalization signal. The transmembrane domain of beta also participates in
endocytosis. In conclusion, several weak endocytic determinants can be
responsible for the rapid internalization of a membrane protein.
PMID- 9654107
TI - In vitro schedule-dependent interaction between paclitaxel and SN-38 (the active
metabolite of irinotecan) in human carcinoma cell lines.
AB - Paclitaxel and irinotecan are important new anticancer agents. The combination of
these two agents has been considered for use against a variety of advanced solid
tumors. Since the schedule-dependent effects of this combination may be crucial
to its use, we studied the interaction of paclitaxel and SN-38 (the active
metabolite of irinotecan) in various schedules in four human cancer cell lines in
culture. Cell growth inhibition after 5 days was determined using an MTT assay.
The effects of drug combinations at the IC80 level were analyzed by the
isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h
produced antagonistic (subadditive and protective) effects in the human lung
cancer cell line A549, the breast cancer cell line MCF7, and the colon cancer
cell line WiDr, and produced additive effects in the ovarian cancer cell line
PA1. Sequential exposure to paclitaxel for 24 h followed by SN-38 for 24 h, and
the reverse sequence, produced additive effects in all four cell lines. These
findings suggest that sequential administration, not simultaneous administration,
may be the appropriate schedule for the therapeutic combination of paclitaxel and
irinotecan. Continued preclinical and clinical studies should provide further
insights and assist in determining the optimal schedule for this combination in
clinical use.
PMID- 9654108
TI - Clinical pharmacokinetics of intravenous treosulfan in patients with advanced
solid tumors.
AB - Treosulfan (L-threitol- 1,4-bis-methanesulfonate, Ovastat) is a prodrug of a
bifunctional alkylating agent with activity in ovarian carcinoma and other solid
tumors. For a clinical and pharmacology study, patients with advanced,
refractory, or resistant solid tumors were treated with a single-dose intravenous
30-min infusion of 8 or 10 g/m2 treosulfan. A sensitive method for the
determination of treosulfan in plasma and urine by reverse-phase high-performance
liquid chromatography was developed. A total of 14 plasma and urine treosulfan
pharmacokinetics determinations were analyzed in the 8-g/m2 group and 7 were
analyzed in the 10-g/m2 group, the maximum tolerated dose for this group of
pretreated patients. The terminal half-life of treosulfan was in the range of 1.8
h. AUC and Cmax values were significantly (P < 0.01) higher in the 10-g/m2 group
(AUC 708+/-168 versus 977+/-182 microg ml(-1) h, Cmax 465+/-98 versus 597+/-94
microg/ml). The mean urinary excretion of the parent compound was about 25% of
the total dose delivered over 48 h (range 5-49%), and about 20% was excreted
during the first 6 h after administration. Currently, a clinical phase I
pharmacokinetics and dose-escalation trial with autologous blood stem-cell
support has been started at 20 g/m2 treosulfan using a 2-h infusion protocol.
PMID- 9654109
TI - Molecular characterization of human acute leukemia cell line resistant to ZD9331,
a non-polyglutamatable thymidylate synthase inhibitor.
AB - ZD9331 is a non-polyglutamatable, potent quinazoline antifolate inhibitor of
thymidylate synthase (TS). In an effort to clarify the exact mechanism of
resistance to this novel TS inhibitor, we examined the molecular alterations in
its target enzyme TS, the transport protein (reduced folate carrier, RFC), and
folylpolyglutamate synthetase (FPGS) in a human acute lymphoblastic leukemia cell
line, MOLT-3, made resistant to ZD9331. A 310-fold resistant subline was
established after 6 months exposure to the drug at concentrations up to 7 microM,
and was designated MOLT-3/ ZD9331. MOLT-3/ZD9331 showed crossresistance to CB3717
(4.8-fold), raltitrexed (63-fold) and methotrexate (MTX) (120-fold), but retained
sensitivity to trimetrexate (0.88-fold). The resistant cells demonstrated
impaired initial cellular uptake and low accumulation of [3H]MTX in accordance
with a decreased expression of RFC1, suggesting the downregulation of RFC.
However, Southern blot analysis demonstrated no change in gene copy number nor
gross rearrangement of RFC1 in the resistant cells. In addition, MOLT-3/ZD9331
showed amplification of the TS gene with a concomitantly increased level in the
gene expression. In contrast, the expression of FPGS did not alter. These results
demonstrate that continuous exposure of the cells to ZD9331 leads not only to a
decreased expression of RFC1 but also to TS gene amplification and
overexpression. The resistant mechanisms are likely to be regulated both at a
genetic and a transcriptional level for different resistance phenotypes in the
ZD9331-resistant MOLT-3 cells.
PMID- 9654110
TI - Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer.
Cancer Research Campaign Phase I/II Clinical Trials Committee.
AB - PURPOSE: D-Limonene is a natural monoterpene with pronounced chemotherapeutic
activity and minimal toxicity in preclinical studies. A phase I clinical trial to
assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in
patients with advanced cancer was followed by a limited phase II evaluation in
breast cancer. METHODS: A group of 32 patients with refractory solid tumors
completed 99 courses of D-limonene 0.5 to 12 g/m2 per day administered orally in
21-day cycles. Pharmacokinetics were analyzed by liquid chromatography-mass
spectrometry. Ten additional breast cancer patients received 15 cycles of D
limonene at 8 g/m2 per day. Intratumoral monoterpene levels were measured in two
patients. RESULTS: The MTD was 8 g/m2 per day; nausea, vomiting and diarrhea were
dose limiting. One partial response in a breast cancer patient on 8 g/m2 per day
was maintained for 11 months; three patients with colorectal carcinoma had
prolonged stable disease. There were no responses in the phase II study. Peak
plasma concentration (Cmax) for D-limonene ranged from 10.8+/-6.7 to 20.5+/-11.2
microM. Predominant circulating metabolites were perillic acid (Cmax 20.7+/-13.2
to 71+/-29.3 microM), dihydroperillic acid (Cmax 16.6+/-7.9 to 28.1+/-3.1
microM), limonene-1,2-diol (Cmax 10.1+/-8 to 20.7+/-8.6 microM), uroterpenol
(Cmax 14.3+/-1.5 to 45.1+/-1.8 microM), and an isomer of perillic acid. Both
isomers of perillic acid, and cis and trans isomers of dihydroperillic acid were
in urine hydrolysates. Intratumoral levels of D-limonene and uroterpenol exceeded
the corresponding plasma levels. Other metabolites were trace constituents in
tissue. CONCLUSIONS: D-Limonene is well tolerated in cancer patients at doses
which may have clinical activity. The favorable toxicity profile supports further
clinical evaluation.
PMID- 9654112
TI - Phase I study of E7010.
AB - E7010 is a novel sulfonamide which was discovered using slow-growing colon 38
carcinoma cells as a screening model. E7010 exhibits a broad spectrum of
antitumor activity against human tumor xenografts. The mechanism of action is by
arresting the progression of cells in M phase of the cell cycle by inhibiting
tubulin polymerization. The objective of this phase I study was to determine the
maximum allowable dose (MAD), toxicity, and pharmacokinetics of single or 5-day
repeated doses of E7010. In the single-dose study, E7010 was administered orally
to 16 patients at doses ranging from 80 to 480 mg/m2. The dose-limiting toxicity
was peripheral neuropathy at a dose of 480 mg/m2. Hematological and
gastrointestinal toxicities were mild. In the 5-day repeated-dose study, 41
patients were given E7010 at doses ranging from 30 to 240 mg/m2 per day. The dose
limiting toxicities were peripheral neuropathy and intestinal paralysis.
Gastrointestinal toxicity was dose-dependent but not severe. Hematological
toxicity was not dose-dependent. Pharmacokinetic analysis in the single-dose
study showed a rapid increase in the plasma levels of the drug after
administration, followed by disappearance with a t1/2 of 4.4-16.6 h. The
variation in area under the plasma concentration-time curve (AUC) between the
patients was small and increased in a dose-dependent manner. Total drug recovery
in urine 72 h after administration was 77.8+/-11.4%, indicating that E7010 has
favorable absorption and elimination profiles. The changes in the plasma levels
of E7010 on day 5 in the 5-day repeated-dose study were almost the same as those
on day 1, indicating that the drug did not accumulate. In the single-dose study,
spinal cord metastasis exhibited a 74% reduction in a patient with uterine
sarcoma and a minor response (MR) was observed in a pulmonary adenocarcinoma
patient. In the 5-day repeated-dose study decreases in the tumor markers
carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) were
observed in a patient with stomach cancer and in a patient with recurrent uterine
cervical carcinoma, respectively. The recommended phase II doses are 320 mg/m2
for a single-dose study and 200 mg/m2 per day for a 5-day repeated-dose study.
Since the activity of E7010 is time-dependent, i.e. a certain concentration of
E7010 is required for more than 12 h to suppress the growth of P388 leukemia
cells, it is recommended that subsequent phase I/II studies be conducted using a
divided dose schedule in order to maintain the blood level of E7010.
PMID- 9654111
TI - Increased 9-aminocamptothecin dose requirements in patients on anticonvulsants.
NABTT CNS Consortium. The New Approaches to Brain Tumor Therapy.
AB - BACKGROUND: High grade astrocytomas remain uniformly fatal despite aggressive
surgery and radiotherapy. As existing chemotherapeutic agents are of limited
benefit, clinical trials are underway to screen new drugs, such as 9
aminocamptothecin (9-AC), for activity in high grade astrocytomas. PURPOSE: This
study was designed to estimate the efficacy of 9-AC in patients with newly
diagnosed glioblastoma multiforme and recurrent high grade astrocytomas. The
planned dose of 9-AC for this trial was 850 microg/m2 per 24 h as a 72-h
continuous intravenous infusion every 2 weeks. This was the maximum tolerated
dose (MTD) on this schedule in multiple phase I studies in patients with systemic
malignancies. However, we found this dose subtherapeutic in our patient
population. As a result, the purpose of the study was altered to determine the
MTD. METHODS: A group of 32 patients were studied using 850 microg/m2 per 24 h
with a provision to escalate to 1000 microg/m2 per 24 h if the first three cycles
of 9-AC were without significant hematologic toxicity. Once it was determined
that myelosuppression did not occur in patients on anticonvulsants, dose
escalations were initiated using the continual reassessment method. Dose
escalations were conducted independently in newly diagnosed and recurrent
patients and in those taking and not taking hepatic enzyme-inducing
anticonvulsants. Pharmacologic studies were conducted during the first cycle of 9
AC. Toxicity was determined using the NCI common toxicity criteria and efficacy
was assessed using serial volumetric brain scans. RESULTS: 9-AC was administered
to 59 patients, 31 with newly diagnosed glioblastoma multiforme and 28 with
recurrent high grade astrocytomas. No grade III-IV myelosuppression was noted in
the 29 patients (128 cycles) on phenytoin, carbamazepine, phenobarbital, and/ or
valproic acid who received 850 microg/m2 per 24 h. In contrast, two of three
patients (five cycles) who were not taking anticonvulsants developed grade IV
myelosuppression. Steady-state total 9-AC plasma levels were lower in patients on
anticonvulsants (median 25.3 nM) than in patients who were not taking
anticonvulsants (median 76.5 nM). Dose escalations performed in 27 additional
patients determined the MTD in patients taking anticonvulsants to be 1776
microg/m2 per 24 h for patients with newly diagnosed tumors and 1611 microg/m2
per 24 h for patients with recurrent disease. CONCLUSIONS: We describe a new and
unexpected drug interaction between 9-AC and anticonvulsants. This is similar to
recent findings with paclitaxel, and suggests that higher than "usual" doses of
some chemotherapeutic agents are required in patients on anticonvulsants.
Prospectively defined dose escalations and pharmacologic studies are essential
for the careful evaluation of new chemotherapeutic agents in patients with brain
tumors.
PMID- 9654113
TI - Time dependency of hematopoietic growth factor coupled to chronotoxicity of
carboplatin.
AB - A growing body of data suggests that cancer therapy may be improved and toxicity
reduced by administration of antineoplastic agents and cytokines at carefully
selected times of the day. The time-dependent effects of each of the drugs have
been documented, but not their mutual time dependencies. In the present studies
we sought to determine the best time for granulocyte colony-stimulating factor (G
CSF) administration after carboplatin treatment. Carboplatin was injected in
different groups of ICR mice at four different circadian stages for 5 consecutive
days. Mice were synchronized with an alternation of 12 h of light (from 6:00 a.m.
to 6:00 p.m.) and 12 h of darkness. After the last injection, peripheral WBCs of
three mice from each group were counted every 4 h over a 24-h period. Bone marrow
toxicity was estimated with the mean 24-h WBC count. The most severe leukopenia
occurred in the group injected at 3:00 p.m. - 9 h after light onset. The second
set of experiments evaluated the time-dependent effect of G-CSF when singly
injected or given after carboplatin injections for 5 days only at 3:00 p.m. G-CSF
was injected into various groups on days 8 and 9 at the same four different
circadian stages. On the 10th day after the first injection, peripheral WBCs of
three mice from each group were counted every 4 h over a 24-h period. Time
dependent effects were observed when G-CSF was injected as a single agent. When G
CSF was given at various times to the group with the most severe carboplatin
induced leukopenia, peripheral WBC count recovery was monitored at all injection
times; it reached its highest level (exceeding even that of the control) when G
CSF was injected at 3:00 a.m. Dosing times of both chemotherapy and growth factor
are relevant for optimization of carboplatin's hematologic tolerability.
PMID- 9654114
TI - Phase I study of oral JM216 given twice daily.
AB - JM216 [bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV)] is an oral
platinum complex that is currently in phase II trials in ovarian cancer and lung
cancer on a daily-times-5 schedule. This trial examined an alternative schedule
of two doses given 12 h apart, which may be better tolerated by patients. A total
of 19 patients were given 50 cycles of treatment at doses ranging from 150 to 350
mg/m2 b.i.d. The study was stopped before the MTD was reached due to non-linear
pharmacokinetics. Toxicity was similar to that encountered in previous phase I
studies, with nausea, vomiting and diarrhoea being seen at all dose levels,
although this was generally mild and short-lived, and grade 3 and 4
myelosuppression being seen at dose levels ranging from 250 to 350 mg/m2. There
was no nephro-, oto-, or neurotoxicity, but one patient had an allergic reaction
at 300 mg/m2 on the fifth and sixth cycles. No response was seen, but two
patients with mesothelioma had stable disease and received six cycles. There was
considerable interpatient variability in plasma pharmacokinetics at all dose
levels. There was no relationship between dose and AUC (dose 1 and dose 2) or
Cmax after dose 1. In a limited number of patients the first dose was given in
the morning rather than in the evening, apparently resulting in lower AUC, Cmax
and Tmax values at the 250-mg/m2 dose level, but this was not seen in one patient
at 300 mg/m2. This study confirms that the pharmacokinetics of JM216 is non
linear and highly variable due to saturable absorption and that the daily times 5
schedule is the optimal schedule for further phase II trials.
PMID- 9654115
TI - Analytical and biological inequivalence of two commercial formulations of the
antitumor agent bleomycin.
AB - Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at
least 55-75% bleomycin A2 and 25-32% bleomycin B2 fractional composition. Two
bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb
Oncology, Princeton, N.J.) and bleomycin HCI (Tianjin Hebei Pharmaceutical,
Tianjin, China) were compared analytically and biologically. Reverse-phase high
performance liquid chromatography (HPLC) analyses using the USP methodology
showed that Blenoxane contained primarily (69%) bleomycin A2 and 29.3% bleomycin
B2. In contrast, Tianjin-supplied bleomycin HCI contained 97% bleomycin A5
fraction. In vitro tumor cell growth inhibition assays showed equivalent activity
in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L
1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16
melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor
growth inhibition at the expense of greater drug-induced lethality at higher dose
levels. These studies show there are significant differences in two international
bleomycin formulations. These compositional differences lead to altered biologic
effects.
PMID- 9654116
TI - Evaluation of the linearity of docetaxel pharmacokinetics.
AB - The taxanes, paclitaxel and docetaxel, have favorable response rates in patients
with breast, gynecologic, and lung cancers and have demonstrated activity against
a variety of malignancies. In human trials, paclitaxel pharmacokinetics are
nonlinear and are best fit by a three-compartment model with nonlinear
distribution into the second compartment as well as nonlinear elimination. This
finding is important for patients receiving paclitaxel at high doses or as a
short infusion, as it results in disproportionately high peak concentrations and
delayed elimination. The presence of nonlinear processes in docetaxel
pharmacokinetics has not previously been examined. Therefore, plasma
concentration data obtained from 53 patients receiving docetaxel at 55-115 mg/m2
over 1-24 h as part of phase I studies were modeled using the nonlinear three
compartment model found most suitable for paclitaxel and the results were
compared with those obtained using the linear version. Docetaxel disposition was
best described by the three-compartment nonlinear model in 28 of 53 data sets
(53%). However, the difference in curve fit observed between the two models was
modest (did not improve Akaike criteria) and unlikely to be of relevance. This
study suggests that nonlinear processes in docetaxel pharmacokinetics may exist,
but, unlike the case of paclitaxel, they are not likely to have a significant
impact at the dose and administration schedule used in routine clinical practice
(60-100 mg/m2 given over 1 h by infusion). The presence of nonlinear docetaxel
pharmacokinetics at doses above 115 mg/m2 will have to be determined in case of
further dose escalation.
PMID- 9654117
TI - Renal toxicity of the anticancer drug fostriecin.
AB - PURPOSE: Fostriecin is an inhibitor of topoisomerase II catalytic activity. In a
phase I trial we observed renal toxicity, documented as a rise in serum
creatinine, which was reversible and non-dose-limiting. The purpose of this study
was a detailed analysis of this toxicity. METHODS: A total of 20 patients
received fostriecin as a 1-h i.v. infusion daily x 5 at doses ranging from 2 to
20 mg/m2 per day. Serum creatinine determination and urinalysis were performed
daily during drug administration. Renal hemodynamics were measured by means of
clearance studies using 125I-iothalamate and (131)I-hippuran in eight patients at
doses of > or =4 mg/m2 per day at baseline, on day 3 or 4 during the first
course, and 3 weeks after the second course. RESULTS: The rise in serum
creatinine was maximal after one to two doses despite continued administration.
This increase showed no correlation with the dose level at fostriecin doses of >
or =4 mg/m2 per day. Urinary beta2-microglobulin concentrations increased 150
fold (median), which is compatible with impaired tubular reabsorption. The median
change in the glomerular filtration rate (GFR) was -36% (range -28% to -44%),
that in effective renal plasma flow (ERPF) was -23% (range -11% to -36%), and the
filtration fraction (FF) decreased in all patients during the first course of
treatment. The values measured 3 weeks after the second course, however, did not
differ from baseline. CONCLUSIONS: Fostriecin induces reversible renal
hemodynamic changes compatible with renal tubular damage.
PMID- 9654118
TI - Comparison of the pharmacokinetics and efficacy of irinotecan after
administration by the intravenous versus intraperitoneal route in mice.
AB - Irinotecan (CPT-11) is a new drug active in colorectal cancer. A comparison was
made of the efficacy and pharmacokinetics of CPT-11 after i.p. versus i.v.
administration to mice. We found that i.p. administration of CPT-11 to mice
bearing C26 colon cancer was more efficient and less toxic than i.v.
administration; a 100-mg i.p. dose induced an increase in life span equivalent to
that produced by a 300-mg i.v. dose, and toxic deaths appeared after doses of 400
mg/kg given i.v. and 800 mg/kg given i.p. Pharmacokinetic parameters of CPT-11
and SN-38 were compared after i.v. or i.p. administration in mice bearing P388
leukemia ascites. Peritoneal CPT-11 and SN-38 AUC values were higher after i.p.
administration than after i.v. injection. Plasmatic AUC values remained
equivalent. Moreover, peritoneal CPT-11 clearance was 10-fold lower after i.p.
versus i.v. administration. If the survival and pharmacologic advantage of i.p.
CPT-11 in the murine model considered can be translated to a safe and practical
mode of therapy in patients and if local toxicity does not prove to be a major
adverse effect, then a potentially useful agent could be added to the drugs known
to be active when given by the i.p. route for adjuvant therapy in colon cancer.
PMID- 9654119
TI - Glucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA
damaging agents on rat tibial growth-plate chondrocytes in vitro.
AB - It is apparent that cytotoxic chemotherapy used to treat childhood malignancies
has a major impact on subsequent growth. Our initial studies have demonstrated a
direct adverse effect of individual glucocorticoids and cytotoxic agents on the
proliferative capacity of rat tibial growth-plate chondrocytes in vitro. In the
present study we investigated the interaction between these classes of agents
using in vitro cultures of chondrocytes and examined the potential of these cells
to recover from the adverse effects of the drugs as applied either alone or in
combination. The glucocorticoids prednisolone and dexamethasone significantly
reduced the growth rate of chondrocytes when present in cultures for 3 days. The
growth rate increased following the removal of prednisolone and dexamethasone
from cultures and reached 83.9+/-0.8% and 62.4+/-4.0%, respectively, of the
control values after 11 days of culture. In contrast, cell numbers were
significantly reduced when the DNA-damaging agents cisplatin, carboplatin,
etoposide or actinomycin-D were present in cultures for 3 days. Very little
recovery of cell growth was observed after removal of the drugs from cultures,
with cell loss occurring in the cisplatin- and actinomycin-D-treated cultures.
However, pretreatment of chondrocytes with either of the glucocorticoids
completely ameliorated the cytotoxic effects of etoposide and carboplatin and
significantly reduced those of cisplatin and actinomycin-D. Recovery of the cells
treated with a combination of glucocorticoid and DNA-damaging agent was
demonstrated by a significant increase in their ability to form colonies in
suspension culture. Colony numbers were increased by a factor of between 5 and 80
as compared with the cells receiving medium alone followed by DNA-damaging agent.
The glucocorticoids offer a protective effect in terms of the reduced
cytotoxicity of DNA-damaging agents and improve the subsequent clonogenicity and
recovery of growth-plate chondrocytes. This has important implications for
treatment schedules involving both cytotoxic agents and glucocorticoids in
childhood malignancies.
PMID- 9654120
TI - Indirect evidence for structural changes coupled with QB-. formation in
photosystem II.
AB - The thermal blockage of QA-. oxidation was analysed in PS II membrane fragments
by monitoring flash-induced changes of the relative fluorescence quantum yield as
a function of temperature. The results obtained reveal: (a) in dark-adapted
samples the fraction of QA-. that is not reoxidised within a time domain of 10 s
after the actinic flash increases with lowering the temperature (half-maximum
effect at 250-260 K), (b) at low temperatures where QA-. generated in dark
adapted samples remains almost completely reduced, a significant extent of QA-.
reoxidation arises when samples are used that were preilluminated at room
temperature by one saturating flash followed by rapid freezing before performing
the experiment, and (c) the extent of QA-. that is reoxidised at 258 K exhibits a
characteristic binary oscillation as a function of the number of preillumination
flashes given at room temperature. Based on these data it is inferred that QB and
QB-. are located at different equilibrium positions in the QB site. As a
consequence the formation of QB-. is coupled with significant structural changes
that require sufficient flexibility of the protein matrix. This general feature
corresponds with a recently proposed model for the acceptor side reactions of
anoxygenic bacteria [Stowell, M.H.B., McPhillips, T.M., Rees, D.C., Soltis, S.M.,
Abresch, E. and Feher, G., Science 276 (1997) 812-816].
PMID- 9654121
TI - Non-glycosylated human B7-1(CD80) retains the capacity to bind its counter
receptors.
AB - Though the cell surface-associated costimulator B7-1(CD80) is known to be highly
N-glycosylated, the functional significance of this N-glycosylation has not been
evaluated. Two experimental approaches were taken to assess the influence of N
glycosylation on human B7-1 function. First, stable K562 transfectants expressing
human B7-1 were treated with the N-glycosylation inhibitor tunicamycin. This
treatment reduced the levels of B7-1 at the cell surface as judged by both
indirect immunofluorescence/flow cytometry and immunoprecipitation analyses.
Significantly, the non-glycosylated cell surface-associated B7-1 on tunicamycin
treated cells retained the capacity to bind CTLA-4 x Ig, a soluble derivative of
the CTLA-4(CD152) counter-receptor. Second, experiments were performed with
bacterially-produced non-glycosylated derivatives of human B7-1, comprising
either the complete B7-1 extracellular domain (hB7-1 x ed) or the membrane
proximal IgC-homologue domain of B7-1 in isolation (hB7-1 x IgC). While the hB7-1
x IgC derivative failed to bind to CTLA-4, the larger hB7-1 x ed derivative
associated with CTLA-4 x Ig in cell-free binding assays. Futhermore, recombinant
hB7-1 x ed effectively blocked B7-1-mediated costimulation in an in vitro T cell
proliferation assay, suggesting that this soluble non-glycosylated B7-1
derivative is capable of engaging CD28, the B7 counter-receptor implicated in T
cell activation. Taken together, these data indicate that the N-glycosylation of
B7-1 is not required for its association with counter-receptors. Moreover, the
findings pave the way for the therapeutic use of recombinant bacterial B7-1
derivatives as competitive inhibitors of B7-mediated signals.
PMID- 9654122
TI - The visual cycle retinol dehydrogenase: possible involvement in the 9-cis
retinoic acid biosynthetic pathway.
AB - The 11-cis-retinol dehydrogenase (11-cis-RoDH) gene encodes the short-chain
alcohol dehydrogenase responsible for 11-cis-retinol oxidation in the visual
cycle. The structure of the murine 11-cis-RoDH gene was used to reinvestigate its
transcription pattern. An 11-cis-RoDH gene transcript was detected in several non
ocular tissues. The question regarding the substrate specificity of the enzyme
was therefore addressed. Recombinant 11-cis-RoDH was found capable of oxidizing
and reducing 9-cis-, 11-cis- and 13-cis-isomers of retinol and retinaldehyde,
respectively. Dodecyl-beta-1-maltoside used to solubilize the enzyme was found to
affect the substrate specificity. This is the first report on a visual cycle
enzyme also present in non-retinal ocular and non-ocular tissues. A possible role
in addition to its role in the visual cycle is being discussed.
PMID- 9654123
TI - A study on reducing substrates of manganese-oxidizing peroxidases from Pleurotus
eryngii and Bjerkandera adusta.
AB - A novel peroxidase, oxidizing Mn2+ and different aromatic compounds, was
isolated. Hydroquinones, substituted phenols, dyes, other aromatic compounds and
Mn2+ were compared as reducing substrates, and conclusions presented in the light
of a molecular model built by homology modeling. The enzymes showed the fastest
reaction rates with Mn2+, but the highest affinity corresponded to hydroquinones
and dyes. Oxidation of Reactive Black 5 (an azo-dye not oxidized by Mn3+) was non
competitively inhibited by Mn2+. These findings, together with identification of
putative Mn-binding site (involving Glu36, Glu40, Asp175 and inner heme
propionate) and long-range electron transfer pathways, indicate that different
sites are involved in substrate oxidation.
PMID- 9654124
TI - Requirement of membrane-proximal amino acids in the carboxyl-terminal tail for
expression of the rat AT1a angiotensin receptor.
AB - A series of deletion mutants was created to analyze the function of the membrane
proximal region of the cytoplasmic tail of the rat type 1a (AT1a) angiotensin
receptor. In transiently transfected COS-7 cells, the truncated mutant receptors
showed a progressive decrease in surface expression, with no major change in
binding affinity for the peptide antagonist, [Sar1,Ile8]angiotensin II. In
parallel with the decrease in receptor expression, a progressive decrease in
angiotensin II-induced inositol phosphate responses was observed. Alanine
substitutions in the region 307-311 identified the highly conserved
phenylalanine309 and adjacent lysine residues as significant determinants of AT1a
receptor expression.
PMID- 9654125
TI - Rat dipeptidyl peptidase IV (DPP IV) exhibits endopeptidase activity with
specificity for denatured fibrillar collagens.
AB - Dipeptidyl peptidase IV (DPP IV, CD 26) is an integral membrane serine protease
exhibiting a well characterized exopeptidase activity. The present study shows
that DPP IV also possesses a novel gelatinase activity and therefore
endopeptidase activity, which was directly demonstrated by gelatin zymography.
Protease inhibitor profile analysis showed that the endo- and exopeptidase
activities of DPP IV share a common active site. Substrate specificity was
detected for denatured collagen types I, II, III and V suggesting that DPP IV
might contribute to collagen trimming and metabolism. On the basis of these data
we propose that DPP IV and the recently sequenced gelatinolytic seprase
(FAPalpha) represent a new subfamily of gelatinolytic integral membrane serine
proteases.
PMID- 9654126
TI - Purification and characterization of alkaline phosphatase containing
phosphotyrosyl phosphatase activity from the bacterium Prevotella intermedia.
AB - A novel alkaline phosphatase, designated PiALP, has been purified and
characterized from Prevotella intermedia ATCC 25611, an anaerobe implicated in
progressive periodontal disease. The enzyme was a homodimer of apparently
identical subunits of Mr 54 kDa. Thiol-reducing agents completely inhibited the
purified enzyme. The enzyme was highly stable even at 80 degrees C. It exhibited
substantial activity against tyrosine-phosphate-containing Raytide. The
phosphatase activity was sensitive to orthovanadate and Zn2+ but highly resistant
to okadaic acid. The amino acid sequence of peptides derived from PiALP showed a
high degree of identity (65%) with alkaline phosphatases from Zymomonas mobilis
and Synechococcus. The present results imply that PiALP might represent a new
family of alkaline phosphotyrosyl phosphatases which has not been described
previously.
PMID- 9654127
TI - Sequence and functional characterization of RNase P RNA from the chl alb
containing cyanobacterium Prochlorothrix hollandica.
AB - Only a few complete sequences and very limited functional data are available for
the catalytic RNA component of cyanobacterial RNase P. The RNase P RNA from the
chl alb containing cyanobacterium Prochlorothrix hollandica belongs to a rarely
found structural subtype with an extended P15/16 domain. We have established
conditions for optimal in vitro ribozyme activity, and determined the kinetic
parameters for cleavage of pre-tRNA(Tyr). Analysis of pre-tRNA mutants revealed
that the T-stem sequence only plays a modulating role, whereas the CCA end is
essential for efficient product formation.
PMID- 9654128
TI - Alternative promoter usage and tissue specific expression of the mouse
somatostatin receptor 2 gene.
AB - We have cloned the 5' upstream regulatory region of the mouse somatostatin
receptor 2 gene. Its genomic organization is novel among all somatostatin
receptor genes. It contains two previously unrecognized exons, separated by
introns larger than 25 kb, and three tissue and cell specific alternative
promoters. The first promoter in front of exon 1 is active only in AtT-20 tumor
cells. The second promoter, located 5' to exon 2, is used in brain, pituitary,
adrenals, pancreas, NG 108-15 and AtT-20 cells. Furthermore, it contains putative
DNA elements for regulation by glucocorticoids, estradiol and cAMP. A third
promoter, located in exon 3, is additionally used in lung, kidney and spleen.
PMID- 9654129
TI - TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a
common functional element: implications for its regulation in inflamed cartilage.
AB - Cartilage matrix is stabilised by the interactions of proteins with hyaluronan
(HA). We compare the pH dependences of HA binding by aggrecan, link protein and
TSG-6. Aggrecan and link protein exhibit maximal binding across a wide pH range
(6.0-8.0). TSG-6, a protein that is only produced during inflammation, binds
maximally at about pH 6.0 but shows a dramatic loss of function with increasing
pH. TSG-6 also interacts with aggrecan, with a similar pH dependence, and this
can be inhibited by HA. Thus, a common binding surface on TSG-6 may be involved
in HA and aggrecan binding. We propose that TSG-6 is involved in matrix
dissociation and that this is regulated by pH gradients in cartilage.
PMID- 9654130
TI - Abscisic acid maintains S-type anion channel activity in ATP-depleted Vicia faba
guard cells.
AB - The plant hormone abscisic acid (ABA) regulates important developmental and
stress responses. Recent data show that ABA activates phosphorylation events, but
whether dephosphorylation events are post-translationally regulated by ABA or
whether these are constitutive remains unknown. Slow anion channels in the plasma
membrane of guard cells have been proposed to play an important role during ABA
induced stomatal closing. Anion channels are deactivated by removal of cytosolic
ATP. However, when guard cells were treated with ABA and depleted of ATP, anion
currents remained active. Subsequent removal of extracellular ABA caused
deactivation of currents. Deactivation of currents was reversed by reintroduction
of cytosolic MgATP. These data show that anion channels are regulated by ABA even
in the absence of cytosolic ATP required for kinase-induced phosphorylation
events and that anion channel activity is maintained by ABA under conditions that
favor dephosphorylation-induced deactivation. Furthermore, channel activation
proceeded at high ATP concentrations with nanomolar cytosolic Ca2+ showing a Ca2+
independent final step in anion channel activation.
PMID- 9654131
TI - Evidence that protein kinase A activity is required for the basal and tax
stimulated transcriptional activity of human T-cell leukemia virus type-I long
terminal repeat.
AB - The present study was undertaken to investigate the role of protein kinase A
(PKA) in the control of human T-cell leukemia virus type-I (HTLV-I) long terminal
repeat (LTR) expression, since this issue is still controversial. For this
purpose we employed two human T-cell lines; the Jurkat cells in which long
exposure to diBu-cAMP severely down-regulated the catalytic subunit of PKA (PKA
C), and H-9 cells in which such exposure markedly increased PKA-C level.
Transient transfection assays revealed that addition of diBu-cAMP 1 h before or
after transfection profoundly increased HTLV-I LTR directed CAT expression and
synergistically enhanced its stimulation by the viral transactivator tax gene
product in both cell lines. However longer exposure to diBu-cAMP before
transfection reduced LTR-CAT expression to below its basal level and completely
abolished its stimulation by tax in Jurkat cells, and this diBu-cAMP inhibitory
effect could be abrogated by co-transfection of a PKA-C expressing vector. By
contrast, in H-9 cells, this long exposure to diBu-cAMP continued enhancing LTR
CAT expression and its tax-mediated transactivation, and this stimulatory effect
of diBu-cAMP could be diminished by the PKA-specific inhibitor N-12-(p
bromocinnamylamine)ethyll-5-isoquinolinsulfonamid e (H-89). Notably, in the
absence of diBu-cAMP treatment H-89 reduced LTR-CAT expression to below its basal
level and prevented its stimulation by tax in both cell lines. Together these
findings indicate not only that cAMP-activated PKA stimulates HTLV-I LTR
expression and its transactivation by tax, but even in the absence of PKA
activating signals the basal HTLV-I LTR expression as well as its stimulation by
tax are both dependent on a basal PKA activity.
PMID- 9654132
TI - Resistance to nitrophenolic herbicides and metronidazole in the cyanobacterium
Synechocystis sp. PCC 6803 as a result of the inactivation of a nitroreductase
like protein encoded by drgA gene.
AB - Dinoseb is a herbicide known to inhibit photosystem II electron transfer like
DCMU, triazine and phenolic-type herbicides. The mutant Din7 of the
cyanobacterium Synechocystis sp. PCC 6803, selected for resistance to dinoseb,
and the mutant Ins2, constructed by the insertion of the kanamycin resistance
cassette into the drgA gene, were cross-resistant to other nitrophenolic
herbicides (DNOC, 2,4-dinitrophenol) and to the cell inhibitor metronidazole but
not to the photosystem II inhibitors DCMU or ioxynil. The Din7 mutant had the
same characteristics of photosystem II inhibition by dinoseb as the wild type.
This result suggested the existence of another site for dinoseb inhibition. The
wild type cells modified dinoseb to a non-toxic product that gave an absorption
spectrum similar to that of dithionite treated dinoseb containing reduced nitro
groups. In contrast, the Din7 mutant did not modify dinoseb. These phenomena were
controlled by the drgA gene encoding a protein which showed similarity to several
enzymes having nitroreductase activity. The addition of superoxide dismutase to
the medium relieved the toxic effect of dinoseb in wild type cells but not in
Din7. It is proposed that in wild type cells of Synechocystis sp. PCC 6803 the
DrgA protein is involved in detoxification of dinoseb via the reduction of the
nitro group(s) and this process is accompanied by the formation of toxic
superoxide anions. Mutations blocking the activity of the DrgA protein lead to
the development of resistance to nitrophenolic herbicides and metronidazole.
PMID- 9654133
TI - Characterization of a gene encoding an abscisic acid-inducible type-2 lipid
transfer protein from rice.
AB - The cloning and sequence analysis of a novel gene that encodes a type 2 non
specific lipid transfer-like protein (LTP) from rice is reported. Sequence
analysis revealed an ORF encoding a protein showing characteristics of the LTP
proteins. However, rice LTP2 is more similar to heterologous LTPs than to rice
LTP1, supporting the existence of two distinct families of plant LTPs. Ltp2 mRNA
is accumulated only in mature seeds. In vegetative tissues, mRNA was only
detected after treatment with abscisic acid (ABA), mannitol or NaCl. Transient
expression experiments that the 61 nucleotides upstream of the TATA box,
containing two ACGT boxes and the motif I, are sufficient for ABA responsiveness
of the Ltp gene.
PMID- 9654134
TI - Thrombin induces the association of cyclic ADP-ribose-synthesizing CD38 with the
platelet cytoskeleton.
AB - The effect of platelet stimulation on the subcellular localization of CD38, a
membrane glycoprotein that catalyses the synthesis of cyclic ADP-ribose from beta
NAD+ was investigated. Treatment of human platelets with thrombin caused the
association of about 40% of the total ADP-ribosyl cyclase activity with the
cytoskeleton, through the translocation of the CD38 molecule from the Triton X
100-soluble to the insoluble fraction. The interaction of CD38 with the
cytoskeleton was a specific and reversible process, mediated by the binding to
the actin-rich filaments and was inhibited by treatment of platelets with
cytochalasin D. This event was regulated by integrin alphaIIb beta3 and platelet
aggregation as it was prevented by the inhibition of fibrinogen binding and was
not observed in platelets from a patient affected by Glanzmann thrombasthenia.
These results demonstrate that the subcellular localization of CD38 can be
influenced by platelet stimulation with physiological agonists, and that membrane
CD38 can interact with intracellular proteins.
PMID- 9654135
TI - Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in
vivo. A role for the caveolin-scaffolding domain.
AB - The p42/44 mitogen-activated protein (MAP)-kinase cascade is a well-established
signal transduction pathway that is initiated at the cell surface and terminates
within the nucleus. More specifically, receptor tyrosine kinases can indirectly
activate Raf, which in turn leads to activation of MEK and ERK and ultimately
phosphorylation of Elk, a nuclear transcription factor. Recent reports have
suggested that some members of p42/44 MAP kinase cascade can be sequestered
within plasmalemmal caveolae in vivo. For example, morphological studies have
directly shown that ERK-1/2 is concentrated in plasma membrane caveolae in vivo
using immunoelectron microscopy. In addition, constitutive activation of the
p42/44 MAP kinase cascade is sufficient to reversibly down-regulate caveolin-1
mRNA and protein expression. However, the functional relationship between the
p42/44 MAP kinase cascade and caveolins remains unknown. Here, we examine the in
vivo role of caveolins in regulating signaling along the MAP kinase cascade. We
find that co-expression with caveolin 1 dramatically inhibits signaling from EGF
R, Raf, MEK-1 and ERK-2 to the nucleus. Using a variety of caveolin-1 deletion
mutants, we mapped this in vivo inhibitory activity to caveolin-1 residues 32-95.
Peptides derived from this region of caveolin 1 also inhibit the in vitro kinase
activity of purified MEK-1 and ERK-2. Thus, we show here that caveolin-1
expression can inhibit signal transduction from the p42/44 MAP kinase cascade
both in vitro and in vivo. Taken together with previous data, our results also
suggest that a novel form of reciprocal negative regulation exists between p42/44
MAP kinase activation and caveolin-1 protein expression, i.e. up-regulation of
caveolin-1 protein expression down-modulates p42/44 MAP kinase activity (this
report) and up-regulation of p42/44 MAP kinase activity down-regulates caveolin-1
mRNA and protein expression.
PMID- 9654137
TI - Cloning and sequencing of ISC1041 from the archaeon Sulfolobus solfataricus MT-4,
a new member of the IS30 family of insertion elements.
AB - A genomic fragment containing the insertion sequence ISC1041 has been cloned by
PCR from the archaeon Sulfolobus solfaricus MT-4, an extremophilic microorganism
which grows at 87 degrees C. The 1038 bp ISC1041 element contains an imperfect 18
nt repeat and a long open reading frame which encodes a polypeptide of 311 amino
acid residues. The translated amino acid sequence shows a significant similarity
to IS30-like transposases. Structural analysis indicates that ISC1041 is a novel
member of the IS30 family and displays the DDE motif not previously seen in
Archaea. This motif is believed to be involved in the integration mechanism of
many mobile elements. As this motif is present in several integrases and
transposases which, despite the lack of overall protein homologies, share
topological homologies to the DDE motif, a common ancestor has been proposed. The
finding of an IS30-like transposase in the archaeal kingdom may have relevance
for horizontal gene transfer.
PMID- 9654136
TI - Coexpression of GTP cyclohydrolase I and inducible nitric oxide synthase mRNAs in
mouse osteoblastic cells activated by proinflammatory cytokines.
AB - Proinflammatory cytokines, a combination of IL-1beta, TNF-alpha, and IFN-gamma,
caused mRNA expression of GTP cyclohydrolase I (GTP-CH), the rate-limiting enzyme
in tetrahydrobiopterin (BH4) biosynthesis, and of inducible nitric oxide synthase
(iNOS) in a well-characterized osteoblastic clone MC3T3-E1 cell line. We found
the expression of the GTP-CH gene in osteoblasts for the first time. The
expression of GTP-CH and iNOS mRNAs was found to be maximal at 3 and 9 h,
respectively. The expression of both genes elicited increases in BH4 and NO
levels. Pharmacological studies using 2,4-diamino-6-hydroxypyrimidine, an
inhibitor of GTP-CH activity, showed that BH4 is involved in the activity of
iNOS, but not in the induction of iNOS mRNA. The results using an inhibitor of
nuclear factor (NF)-kappaB and activating protein-1 (AP-1) activation suggested
that coinduction of the two genes in response to cytokines occurred via
activation of NF-kappaB and AP-1. In MC3T3-E1 cells BH4 and sepiapterin,
producing BH4, could protect against apoptosis, i.e. the degradation of nuclear
DNA in the cells, induced by NO derived from S-nitroso-N-acetyl-D-L
penicillamine. These results suggest that the induction of BH4 together with NO
by proinflammatory cytokines could protect against NO-induced apoptosis in MC3T3
E1 cells.
PMID- 9654138
TI - HrpW of Erwinia amylovora, a new Hrp-secreted protein.
AB - Erwinia amylovora strain CFBP1430 secretes a protein called HrpW in a Hrp
dependent manner. HrpW was detected in culture supernatant of the wild-type
strain grown on solid inducing hrp medium. This protein shares structural
similarities with elicitors of the hypersensitive response such as HrpN of
Erwinia amylovora and PopA of Ralstonia solanacearum. Furthermore, the C-terminal
region of HrpW is homologous to class III pectate lyases. An hrpW mutant is as
aggressive as the wild-type strain on pear and apple seedlings. It elicits the
hypersensitive response on tobacco at a lower concentration than the wild-type
strain.
PMID- 9654139
TI - An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase
suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant.
AB - A cDNA encoding a glutamine amidotransferase and cyclase catalyzing the fifth and
sixth steps of the histidine (His) biosynthetic pathway has been isolated from
Arabidopsis thaliana. The N- and C-terminal domains of the primary structure
deduced from a full-length Arabidopsis hisHF (At-HF) cDNA showed significant
homology to the glutamine amidotransferase and cyclase of microorganisms,
respectively. Effective suppression of the His auxotrophy of a Saccharomyces
cerevisiae his7 mutant with the At-HF cDNA confirmed that the At-HF protein has
bifunctional glutamine amidotransferase (HisH) and cyclase (HisF) activities.
PMID- 9654140
TI - Biochemical characterization of HIV-1 Rev as a potent activator of casein kinase
II in vitro.
AB - The stimulatory effects of several DNA-binding basic proteins (histone and
protamine) and HIV-1 Rev with arginine (Arg)-rich clusters on the activity of
casein kinase II (CK-II) were investigated in vitro. It was found that
recombinant Rev (rRev) and the synthetic oligo-fragments corresponding to the
amino acid sequences of its Arg-rich cluster stimulate CK-II activity in a dose
dependent manner. The activated CK-II phosphorylates several cellular and viral
proteins in HIV-1 infected human MOLT-4 cells, and also phosphorylates HIV-1
structural proteins, including recombinant reverse transcriptase (rRT). These
phosphorylations are selectively inhibited by CK-II inhibitors, such as
quercetin, oGA (a glycyrrhetinic acid derivative) and NCS-chrom (an enediyne
containing antibiotic). The data presented here suggest that HIV-1 Rev acts as an
effective potent activator of CK-II, which may be a cellular mediator promoting
HIV-1 replication in virus-infected cells.
PMID- 9654141
TI - Characterisation of an Arabidopsis cDNA encoding a thylakoid lumen protein
related to a novel 'pentapeptide repeat' family of proteins.
AB - We have cloned an Arabidopsis cDNA encoding a novel thylakoid lumen protein,
P17.4, that has been previously isolated from lumen extracts of spinach
chloroplasts. The protein is synthesised with a bipartite presequence containing
a Sec-type lumen-targeting signal peptide and the precursor protein is imported
into the lumen of pea chloroplasts. The encoded protein is homologous to an
Anabaena protein that is essential for correct glycolipid localisation, and is
also related to at least 16 unassigned open reading frames in Synechocystis. This
family of proteins is characterised by the presence of numerous pentapeptide
repeats with the consensus structure AXLXX, and its members are predicted to be
located in the cytosol, plasma membrane and periplasm/lumen. P17.4 is therefore
the first higher plant member of an extended family of putative cyanobacterial
proteins that may serve important roles in lipid transport or assembly.
PMID- 9654142
TI - Saccharomyces cerevisiae mitochondria can synthesise FMN and FAD from externally
added riboflavin and export them to the extramitochondrial phase.
AB - Evidence is given that mitochondria isolated from Saccharomyces cerevisiae can
take up externally added riboflavin and synthesise from it both flavin
mononucleotide (FMN) and flavin adenine dinucleotide (FAD) probably due to the
existence of the mitochondrial riboflavin kinase already reported and the novel
mitochondria FAD synthetase. Moreover Saccharomyces cerevisiae mitochondria can
export the newly synthesised flavin derivatives to the extramitochondrial phase.
This has been proven to take place with 1:1 stoichiometry with riboflavin
decrease outside mitochondria, thus showing that flavin traffic occurs across the
mitochondrial membranes.
PMID- 9654143
TI - A non-peptide compound which can mimic the effect of thrombopoietin via c-Mpl.
AB - Thrombopoietin (TPO) is a cytokine which plays a central role in megakaryopoiesis
and platelet production by binding to its cell surface receptor, termed c-Mpl. In
the present study, two benzodiazepinones that compete with the binding of TPO to
the extracellular region of c-Mpl were identified, and one of them stimulated the
proliferation of a human TPO-dependent megakaryocytic cell line, UT-7/TPO. It
stimulated the activation of signal transducer and activator of transcription 5
in UT-7/TPO cells. These results suggest that a non-peptide compound can mimic
the effect of TPO via c-Mpl.
PMID- 9654144
TI - The functional properties of DsbG, a thiol-disulfide oxidoreductase from the
periplasm of Escherichia coli.
AB - Genetic studies have recently identified DsbG, a new member of the dsb group of
redox proteins, which catalyze protein disulfide bond formation in the periplasm
of Escherichia coli. We now demonstrate that DsbG functions primarily as an
oxidant during protein disulfide bond formation, which is consistent with the low
stability of its active site disulfide bond. There are indications, however, that
the substrate range of DsbG may be narrower than the other periplasmic oxidative
enzymes, DsbA and DsbC. Our observations further elaborate the pathway of
disulfide bond formation in E. coli.
PMID- 9654145
TI - A novel importin alpha from rice, a component involved in the process of nuclear
protein transport.
AB - In eukaryotes, nuclear proteins that are transported into nuclei have nuclear
localization signals (NLSs), which are recognized by proteins called importin
alpha. We isolated a rice cDNA, #61L, and the corresponding gene that encodes a
protein, which shows significant homology to the importin alpha. Although the
encoded protein had only 23-27% amino acid identity to the importin alphas from
various organisms including plants, the fusion protein with glutathione S
transferase showed a specific binding activity to the NLS of SV40 T-antigen.
These results suggest that the rice #61L protein is a novel importin alpha in
plants.
PMID- 9654146
TI - Purification and characterisation of a new hypothalamic satiety peptide, cocaine
and amphetamine regulated transcript (CART), produced in yeast.
AB - Cocaine and amphetamine regulated transcript (CART) is a newly discovered
hypothalamic peptide with a potent appetite suppressing activity following
intracerebroventricular administration. When the mature rat CART sequence
encoding CART(1-102) was inserted in the yeast expression plasmid three CART
peptides could be purified from the fermentation broth reflecting processing at
dibasic sequences. None of these corresponded to the naturally occurring CART(55
102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102)
has been produced and CART(55-102) was generated by digestion of the precursor
with dipeptidylaminopeptidase-1. All four generated CART peptides have been
characterised by N-terminal amino acid sequencing and mass spectrometry. The CART
peptides contain six cysteine residues and using the yeast expressed CART(62-102)
the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the
four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to
2.0 microg) they all produced a dose dependent inhibition of food intake.
PMID- 9654147
TI - The solution structure of DNA decamer duplex containing the Dewar product of
thymidylyl(3-->5')thymidine by NMR and full relaxation matrix refinement.
AB - The (6-4) adducts and their Dewar isomers play an important role in cytotoxicity
and mutation in skin cells exposed to sunlight. Structural study of the DNA
duplex containing a site-specific photoproduct is an essential step toward
understanding the molecular mechanism of the mutagenesis and the repair activity
of UV-irradiated DNA. Here we use 1H NMR spectroscopy and full relaxation matrix
refinement to investigate the solution structure of the duplex Dewar decamer. We
find that the isomerization of the (6-4) adduct to its Dewar form induces a
substantial change in overall structure of the oligonucleotide duplex.
Contrasting base stacking of two lesion sites results in a large difference in
the structural impacts induced by the two photoproducts, such as differential
disruption of hydrogen bonding at the lesion sites and overall helical bending of
44 degrees by the (6-4) lesion and 21 degrees by the Dewar lesion.
PMID- 9654148
TI - Promoter elements required for sugar-repression of the RAmy3D gene for alpha
amylase in rice.
AB - There is increasing evidence showing that cereal alpha-amylase gene expression is
controlled not only by the classical hormonal regulation, but also by feed-back
sugar repression. We demonstrated by in situ hybridization that the sugar
repression of rice alpha-amylase gene RAmy3D takes place in scutellar epithelium
cells of callus-forming rice embryos. We also used a transient expression system
to study the cis-acting elements involved in the sugar repression of the RAmy3D
promoter activity. Site-directed mutagenesis of the 50-bp nucleotide sequence
from -172 to -123 revealed that consensus sequences of G motif (TACGTA) and
TATCCA T/C motif (GATA motif as its antisense sequence) are responsible for sugar
repression. The promoter sequences required for sugar repression are reported and
discussed.
PMID- 9654149
TI - Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces
cerevisiae.
AB - Wilson disease is a genetic disorder of copper metabolism characterized by the
toxic accumulation of copper in the liver. The ATP7B gene, which encodes a copper
transporting P-type ATPase, is defective in patients with Wilson disease. To
investigate the function of ATP7B, wild type or mutated ATP7B cDNA was introduced
into a yeast strain lacking the CCC2 gene (delta ccc2), the yeast homologue of
ATP7B. Wild type and the H1069Q mutant could rescue delta ccc2, however, the
N1270S mutant could not, reflecting phenotypic variability of Wilson disease. In
addition, the mutant containing only the sixth copper binding domain could rescue
delta ccc2, indicating its functional importance.
PMID- 9654150
TI - LVV- and VV-hemorphins: comparative levels in rat tissues.
AB - Screening of hemorphins in extracts of rat lung, brain, heart and spleen was
carried out. The threshold for detection of hemorphins was 0.01 nmol for spleen
and 0.05 nmol for other tissues. Both the content and the composition of
hemorphins differed significantly in the tissues analyzed. Heart and lung
extracts were rich in these peptides, the content of the most abundant components
reaching 16-44 nmol/g of tissue. In contrast, spleen and brain contained much
lower amounts of hemorphins, i.e. about 0.3-2.6 nmol/g of tissue. The most
represented hemorphin in lung, heart and brain was VV-hemorphin-5, while the
content of other members of the hemorphin family depended significantly on the
tissue analyzed: lung extract was also rich in LVV-hemorphin-5, heart contained
similar amounts of LVV-hemorphin-7 and LVV-hemorphin-5 and brain of LVV-hemorphin
6. In contrast, the hemorphin family in spleen was represented mainly by C
terminally shortened VV-hemorphins, i.e. VV-hemorphin-4 and VV-hemorphin-3. The
levels of hemorphins in all cases were sufficient to activate the opioid
receptors of the respective tissues.
PMID- 9654151
TI - Human substance P receptor expressed in Chinese hamster ovary cells directly
activates G(alpha q/11), G(alpha s), G(alpha o).
AB - Substance P receptor (SPR) stably expressed in Chinese hamster ovary (CHO) cells
stimulates at least three second messenger systems including phosphoinositide
hydrolysis, cyclic AMP (cAMP) formation, and arachidonic acid release. Whether
these second messenger systems are activated via single or multiple G proteins is
not known. Therefore, in the present study we examined whether human SPR (hSPR)
stably expressed in CHO cells activates multiple G proteins. This was achieved by
photoaffinity labeling of G(alpha)-subunits with [32P]azidoanilido-GTP ([32P]AA
GTP) upon hSPR stimulation in CHO-hSPR membranes followed by immunoprecipitation
of the labeled G(alpha)-subunits with antibodies specific for various G(alpha)
subunits. These experiments reveal that hSPR directly activates G(alpha q/11),
G(alpha s) and G(alpha o). While hSPR is known to couple G(alpha q/11), the
present study provides the first evidence that hSPR can also activate G(alpha s)
and G(alpha o) in a mammalian system.
PMID- 9654152
TI - The F420H2:heterodisulfide oxidoreductase system from Methanosarcina species. 2
Hydroxyphenazine mediates electron transfer from F420H2 dehydrogenase to
heterodisulfide reductase.
AB - F420H2-dependent CoB-S-S-CoM reduction as catalyzed by the F420H2:heterodisulfide
oxidoreductase from Methanosarcina strains was observed in a defined system
containing purified F420H2 dehydrogenase from Methanosarcina mazei Go1, 2
hydroxyphenazine and purified heterodisulfide reductase from Methanosarcina
thermophila. The process could be divided into two partial reactions: (1)
reducing equivalents from F420H2 were transferred to 2-hydroxyphenazine by the
F420H2 dehydrogenase with a Vmax value of 12 U/mg protein; (2) reduced 2
hydroxyphenazine acted as electron donor for CoB-S-S-CoM reduction as catalyzed
by the heterodisulfide reductase. The specific activity was 14-16 U/mg protein at
37 degrees C and 60-70 U/mg protein at 60 degrees C. The partial reactions could
be combined in the presence of both enzymes. Under these conditions reduced 2
hydroxyphenazine was rapidly oxidized by the heterodisulfide reductase thereby
producing the electron acceptor for the F420H2 dehydrogenase. Above a
concentration of 50 microM of 2-hydroxyphenazine, the specific activity of the
latter enzyme reached the Vmax value. When other phenazines or quinone
derivatives were used as electron carriers, the activity of F420H2-dependent CoB
S-S-CoM reduction was much lower than the rate obtained with 2-hydroxyphenazine.
Thus, this water-soluble analogue of methanophenazine best mimics the natural
electron acceptor methanophenazine in aqueous systems.
PMID- 9654153
TI - Purification and characterization of alpha-3',4'-anhydrovinblastine synthase
(peroxidase-like) from Catharanthus roseus (L.) G. Don.
AB - An H2O2-dependent enzyme capable of coupling catharanthine and vindoline into
alpha-3',4'-anhydrovinblastine (AVLB) was purified to apparent homogeneity from
Catharanthus roseus leaves. The enzyme shows a specific AVLB synthase activity of
1.8 nkat/mg, and a molecular weight of 45.40 kDa (SDS-PAGE). In addition to AVLB
synthase activity, the purified enzyme shows peroxidase activity, and the VIS
spectrum of the protein presents maxima at 404, 501 and 633 nm, indicating that
it is a high spin ferric heme protein, belonging to the plant peroxidase
superfamily. Kinetic studies revealed that both catharanthine and vindoline were
substrates of the enzyme, AVLB being the major coupling product.
PMID- 9654154
TI - Purification of a novel endothelin-converting enzyme specific for big endothelin
3.
AB - Endothelin-3 (ET-3), a potent vasoactive peptide, is considered to be produced
from big ET-3 by endothelin-converting enzyme (ECE) like the other members of the
endothelin family (ET-1 and ET-2). We purified a novel ECE from bovine iris
microsomes. The purified enzyme, a 140 kDa protein by SDS-PAGE analysis,
converted big ET-3 to ET-3 but not big ET-1, with a Km value of 0.14 microM for
big ET-3. The conversion to ET-3 was confirmed with sandwich EIA by monoclonal
antibodies, the elution profile of HPLC, and intracellular calcium mobilization
in CHO-K1 cells expressing recombinant human ET(B) receptors. The conversion
activity was inhibited by an inhibitor of neutral endopeptidase 24.11 (NEP)
phosphoramidon. These results show that ECE-3 purified from bovine iris is a
novel metalloprotease totally different from ECE-1 or ECE-2, in that the enzyme
is highly specific for big ET-3.
PMID- 9654155
TI - Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in
polycythaemia vera.
AB - We report on long-term therapeutic efficacy and toxicity of recombinant
interferon-alpha 2a (rIFN-alpha) in a series of 38 patients with polycythaemia
vera (PV). In all patients haematocrit was first brought into the normal range by
venesection; rIFN-alpha was then begun at a starting weekly dose of 9,000,000 IU.
Complete response (CR) was defined as persistence of normal haematocrit without
venesection and partial response (PR) as >50% reduction of phlebotomy
requirement. Eleven patients (28.9%) achieved CR and 8 (21.0%) PR. Median
duration of treatment for all responsive patients was 40 months; 12 patients are
still responsive and under treatment after 13, 15, 25, 35, 40, 41, 43, 49, 50,
51, 52 and 52 months of therapy with rIFN-alpha. In responsive patients, rIFN
alpha also normalized leucocyte counts, platelet counts and spleen enlargement;
rIFN-alpha also relieved generalized pruritus in all 10 patients displaying this
symptom. Early toxicity (flu-like syndrome) was observed in 23.6% and late
toxicity (severe weakness) in 13.1% of patients, requiring rIFN-alpha treatment
suspension in all cases. Progression to leukaemia was observed in none of the 10
patients treated only with rIFN-alpha and in one of the 12 who received
alkylating agents before enrolment in this study. According to these data, rIFN
alpha seems to be an effective and safe treatment option for PV.
PMID- 9654156
TI - Plasma erythropoietin by high-detectability immunoradiometric assay in untreated
and treated patients with polycythaemia vera and essential thrombocythaemia.
AB - By using an immunoradiometric method with a stated detection limit of < or =1
IU/l (stated normal reference limit in adults 3.7-16 IU/l) we determined EDTA
plasma erythropoietin (EPO) in 58 patients with polycythaemia vera (PV) and 49
patients with essential thrombocythaemia (ET). At the time of blood sampling, 20
of the PV patients were newly diagnosed and untreated, 23 were treated by
phlebotomy only, and 30 also received myelosuppressive treatment (with 32P,
hydroxyurea or alpha-interferon). Of the ET patients 24 were untreated and 28
received myelosuppressive therapy. For comparison plasma EPO was also determined
in 10 patients with pseudopolycythaemia (PP). In this latter group the results
for plasma EPO agreed well with the cited normal reference limits. The majority
of untreated PV patients (12/20) had undetectable plasma EPO concentration, and
the remainder all had values below the lower normal reference limit. Plasma EPO
in PV was not significantly influenced by phlebotomy therapy. Twelve of the 24
untreated ET patients (50%) had plasma EPO values below the reference interval
(undetectable in 2 patients). The mean EPO concentration was significantly lower
in PV patients receiving phlebotomy therapy than in patients with untreated ET.
In the total material of PV and ET treated with myelosuppressive agents the PV
patients showed significantly lower values for EPO concentration than did
patients with ET. The present results support the view that EPO measurements by
high-detectability methods are diagnostically useful and should be included in
the panel of new criteria for the diagnosis of PV.
PMID- 9654157
TI - Antibodies against platelet glycoproteins and antiphospholipid antibodies in
autoimmune thrombocytopenia.
AB - Autoantibodies against platelet glycoproteins (anti-GP) are found in the majority
of patients with autoimmune thrombocytopenia (AITP) as well as in
thrombocytopenia associated with systemic lupus erythematosus (SLE). Some of
these patients may have anti-phospholipid antibodies (anti-PL). To evaluate the
pathogenetic significance of anti-PL and anti-GP antibodies in AITP and SLE
patients, we investigated anti-cardiolipin (anti-CL), anti-phosphatidylserine
(anti-PS) and anti-GP antibodies (anti-GPIIb-IIIa and anti-GPIb-IX) in 71
patients with AITP and 3 thrombocytopenic patients with SLE. Anti-GP antibodies
were detected in 52 (70%) patients. Fifty-six (73%) patients showed anti-PL
antibodies. Seven patients (6 AITP, 1 SLE) with both anti-GPIIb-IIIa and IgG anti
PL antibodies were followed during treatment with corticosteroids. Antibodies
were measured before treatment and at the time of platelet-peak. Anti-GPIIb-IIIa
antibodies decreased in all or became undetectable in five. In contrast, IgG anti
PS and IgG anti-CL antibodies decreased only moderately or remained positive.
Adsorption experiments, using gelfiltered platelets, erythrocyte (Ec)-inside-out
vesicles and purified GPIIb-IIIa, showed that anti-GP and anti-PL antibodies have
distinct specificities and do not crossreact. We conclude that anti-PL and anti
GP antibodies may be present simultaneously in some patients with immune mediated
thrombocytopenia. Although anti-PS as well as anti-CL antibodies may be
responsible for thrombocytopenia, we speculate that anti-GPIIb-IIIa antibodies
are more related to the severity of thrombocytopenia.
PMID- 9654158
TI - Serum soluble c-kit receptor and expression of c-kit protein and mRNA in acute
myeloid leukemia.
AB - To investigate the clinical role of the soluble form of c-kit receptor (s-kit) in
patients with acute myeloid leukemia (AML), we determined the levels of serum s
kit and expression of c-kit antigens and mRNA in leukemic cells. The serum s-kit
level was measured using ELISA assay in 30 AML patients and 20 normal controls. C
kit antigens of leukemic blasts were stained immunohistologically, and c-kit mRNA
was detected by RT-PCR. The serum s-kit level in M1 and M2 were significantly
increased (p<0.01) and that in M4 or M5 was significantly decreased (p<0.05)
compared to that in the controls. In the comparisons among subtypes of FAB
classification, M1 and M2 showed significantly higher levels than M4 or M5
(p<0.05 and p<0.01, respectively). Both expression of c-kit antigens and mRNA
were observed in M0 (1/4), M1 (2/4) and M2 (6/8), but neither was observed in M4
or M5. The serum s-kit levels were correlated with the absolute number of AML
blasts in peripheral blood (r=0.564, p<0.05). These results indicate that the
serum s-kit level is related to the stage of differentiation of AML blasts in
accordance with the expression of c-kit protein and mRNA in AML blasts, and is
useful for assessment of leukemic cell burden.
PMID- 9654159
TI - Haematopoietic action of flt3 ligand on cord blood-derived CD34-positive cells
expressing different levels of flt3 or c-kit tyrosine kinase receptor: comparison
with stem cell factor.
AB - We compared the effect of human flt3 ligand (FL) and stem cell factor (SCF) on
cord blood (CB)-derived CD34+ cells expressing different levels of flt3 or c-kit
tyrosine kinase (TK) receptor in clonal cell culture. The c-kit receptor was
expressed by 58.5+/-16.7% of CB CD34+ cells (n=19), in which c-kit(high), c
kit(low) and c-kit cell populations could be identified. In contrast, the flt3
receptor (FR) was weakly expressed on 58.6+/-8.3% (n=9) of CB CD34+ cells.
FL+erythropoietin (Epo) failed to support erythroid burst (BFU-E) formation by
any subpopulation of CD34+ cells. However, SCF + Epo supported BFU-E and
erythrocyte-containing mixed (CFU-mix) colony formation from all subpopulations.
Interestingly, FL markedly augmented CFU-mix colony formation supported by
interleukin (IL)-3 + Epo when CD34+c-kit(low) or CD34+FR+ cells were used as the
target. On the other hand, SCF significantly enhanced CFU-mix colony formation
supported by IL-3 + Epo when CD34+c-kit(high) or low and CD34+FR+ cells were
used. The replating potential of CFU-mix supported by IL-3 + Epo+ FL was greater
when CD34+c-kit(low) or CD34+FR+ cells were used. When the CD34+c-kit(low) cells
were used, the number of lineages expressed in secondary cultures of CFU-mix
colonies derived from primary cultures containing IL-3 + Epo + FL or SCF was
significantly larger than when the primary cultures contained IL-3 + Epo.
Furthermore, the number of long-term culture-initiating cells found in CD34+FR+
cells was larger than that in FR cells. CB-derived CD34+c-kit(low) cells
represent a less mature population than c-kit(high) cells, as reported
previously. Therefore, these results indicate that both FL and SCF can act on
primitive multipotential progenitors. However, it is still uncertain whether CB
derived CD34+FR+ cells are less mature than CD34+FR- cells.
PMID- 9654160
TI - Relative distribution of myosin, actin and alpha-actinin in surface-activated,
spreading platelets.
PMID- 9654161
TI - Acute megakaryocytic leukaemia (AML-M7) with myelofibrosis terminating in AML-MO
with concurrent liver fibrosis.
PMID- 9654162
TI - Low dose bolus aminocaproic acid: an alternative to platelet transfusion in
thrombocytopenia?
PMID- 9654163
TI - Serum erythropoietin values and serum iron status during chemotherapy for
leukemia.
PMID- 9654164
TI - Recombinant human erythropoietin for the treatment of refractory anemia in
lymphoproliferative disorders: preliminary results.
PMID- 9654165
TI - Detection of chronic systemic candida infection in leukaemia patients with
febrile neutropenia: value of computer-assisted serial ultrasound documentation.
PMID- 9654166
TI - Have the Fallopian tubes a vital role in promoting fertility?
AB - Diverse lines of evidence suggest that the Fallopian tubes make no overwhelming
contribution to human reproduction other than as a conduit for gametes and
embryos. Even so, bearing in mind global success rates for in vitro fertilization
(IVF) coupled with uterine transplantation of embryos (20% fruitful pregnancies),
the Fallopian tubes may make a subtle contribution to reproductive performance.
The experimental evidence from monkeys and man arguing against an essential role
for the tubes -- at least in individual instances -- would include (1) the
results of Estes' operation, when ovaries are autotransplanted into the uterine
lumen in women with blocked or missing Fallopian tubes and pregnancy ensues; (2)
asynchronous embryo transfer when newly fertilized (pronucleate) eggs
transplanted to the uterus can generate a pregnancy; (3) the transcervical
transfer after IVF of early cleavage stage human embryos into the uterus, with
subsequent establishment of pregnancy; (4) the trans-cervical transfer of human
spermatozoa and oocytes into the uterus to give pregnancy, indicating that
capacitation, fertilization and the earliest stages of embryonic development can
be achieved in the uterus. In endeavoring to explain contrasts between these
successful procedures in primates and their failure in non-primates, perhaps the
simplex uterus in primates compared with a bicornuate or bipartite uterus in
laboratory and farm species has relevance: there is lack of a clear-cut
distinction between the endometrium and endosalpinx in the intra-mural segment
and potential mixing of uterine and tubal fluids. Indeed, the latter may explain
in part a susceptibility to tubal ectopic pregnancy, coupled with proliferating
endometrial fragments in the Fallopian tube.
PMID- 9654167
TI - Synergistic effects of growth hormone and insulin-like growth factor-I on
differentiation and replication of cultured human luteinized granulosa cells.
AB - BACKGROUND: The present study was designed to assess the effects of insulin-like
growth factor-I (IGF-I) alone and in combination with growth hormone (GH) on
differentiation and replication in cultured human granulosa cells. METHODS:
Granulosa cells from patients undergoing in vitro fertilization were isolated and
cultured for 2 days in culture medium with 10% serum, the medium was removed and
the cells were incubated with IGF-I (1, 10 and 100 ng/ml) with or without GH (10
ng/ml) in serum-free medium and in the presence of 3H-methylthymidine (2
microCi/ml). RESULTS: IGF-I alone resulted in a significant dose-dependent
increase in medium estradiol (E2) (p<0.05) and progesterone (P) (p<0.001) and
suppression of IGF-binding protein-1 (IGFBP-1) (p<0.001), without any increase in
[3H]-thymidine incorporation (P=0.10). The combination of IGF-I and GH further
increased the release of E2 (p<0.001), and the amount of [3H]-thymidine
incorporation (p<0.001). CONCLUSION: These results indicate a synergistic effect
of IGF-I and GH on differentiation and replication of human granulosa cells, and
thus support a role of both GH and IGF-I in regulation of ovarian function.
PMID- 9654168
TI - Placental expression of endothelial constitutive nitric oxide synthase mRNA in
pregnancy complicated by preeclampsia.
AB - BACKGROUND: The role of nitric oxide (NO) in normal pregnancy and pregnancy
complicated with preeclampsia (PE) and/or intrauterine growth restriction (IUGR)
still remains questionable. The placenta lacks autonomic innervation, therefore
blood flow must be regulated by humoral and endothelium derived factors. NO is a
potent vasodilator released by endothelial cells. It is synthesized by the
catalytic action of the endothelial constitutive nitric oxide synthase (ecNOS).
Moreover, the synthesis of NO in normal human placental vasculature has already
been established and impairment of the uteroplacental blood flow in pregnancies
complicated by PE and/or IUGR has been demonstrated. DESIGN AND METHODS: The aim
of the present study was to compare the expression of ecNOS mRNA in placenta from
women with complicated and normal pregnancies. Placenta was collected from women
with PE (n = 13) or small for gestational age (SGA) (n = 8), both PE and SGA (n =
7) and normal pregnancies (n = 41). Total nucleic acids were prepared and a
solution hybridization technique was used for mRNA analysis. RESULT: The mRNA
expression of ecNOS was significantly higher (p<0.05) in all groups of
complicated pregnancies compared to normal pregnancies. CONCLUSION: Our findings
indicate that the increased placental expression of ecNOS mRNA might reflect a
compensatory mechanism in the disturbed uterine circulation seen in PE and/or
SGA.
PMID- 9654169
TI - Nuchal translucency as a screening test for chromosomal abnormalities in a
routine first trimester ultrasound examination.
AB - BACKGROUND: To evaluate the implementation of nuchal translucency measurement as
an additional examination within the first trimester routine ultrasound in an
unselected population of women. METHODS: A prospective study in which all
pregnant women during 1994, referred for the first trimester routine ultrasound
scan, were asked to participate. Of a total of 1852 women with a viable
pregnancy, results from 1444 women were evaluated. When a nuchal translucency of
4 mm or more was found, the woman was offered both a genetic amniocentesis in
gestational week 13-15 and an additional ultrasound examination in gestational
week 18-19. RESULTS: Six fetuses had a nuchal translucency of 4 mm or more and
none of these had any chromosomal abnormality. Neither had any of the fetuses in
the study, karyotyped for other reasons, any chromosomal defect and nor was there
any child born with aneuploidy in the study population. No strong relation
between major malformations e.g. abnormalities of the heart and increased nuchal
translucency was found. The fetus with the largest nuchal translucency (=6 mm)
was born healthy. CONCLUSION: The efficacy of nuchal translucency measurement
needs further evaluation before it can be introduced as a screening method in an
unselected pregnant population.
PMID- 9654170
TI - Consumption of anti-D in the erythroblastotic fetus.
AB - BACKGROUND: Maternal serum anti-D is actively transported across the placenta
into the fetal blood where it adheres to D-positive erythrocytes. The anti-D
coated red cells attach to Fc-receptors on fetal reticuloendothelial cells and
are subsequently phagocytosed and hemolysed. It is not known if anti-D is
consumed or recirculated in this process. MAIN QUESTION: Is anti-D in the fetus
consumed in the hemolytic process in the erythroblastotic fetus and can the
consumption be modulated by high-dose immunoglobulins (i.v.IG) given to the
mother? METHODS: Fetal/maternal serum anti-D concentration ratios were calculated
for simultaneously taken blood samples from three groups of Rh(D) immunized
pregnant women; six women with fetuses who were of Rh(D) negative phenotype, 19
women with fetuses who were Rh(D) positive and received no treatment and, seven
women who were treated with i.v.IG because they bore anemic, Rh(D) positive
fetuses. RESULTS: Fetuses with a Rh(D) negative phenotype expressed an increase
in fetal/maternal anti-D concentration ratios from 10 to 55% between 25 and 31
gestational weeks, while Rh(D) positive fetuses without i.v.IG treatment had
stable values at the 10% level between 24 and 35 gestational weeks. During i.v.IG
treatment of the mothers, Rh(D) positive fetuses showed an increase in ratio from
10 to 30% between 26 and 34 gestational weeks. There was a statistically
significant (p<0.001) difference between regression results of the three groups.
CONCLUSIONS: Fetal anti-D is consumed in the hemolytic process and the
consumption can be modulated by i.v.IG given to the mother.
PMID- 9654171
TI - Placental isoferritin in gestational diabetes mellitus.
AB - BACKGROUND: Serum placental isoferritin, an immunosuppressive cytokine like
protein, was found to be elevated in type I diabetes at diagnosis and low in high
risk pregnant women. Further to this observation, the possible role of this
placental product was assessed in pregnant women with gestational diabetes
mellitus. METHODS: A comparative study. One hundred and seventy-four pregnant
women were included in the study: 28 were diagnosed as gestational diabetes
mellitus and 146 were normal controls. MAIN OUTCOME MEASURES: Samples for serum
placental ferritin were measured in the second and third trimesters of pregnancy.
RESULTS: Serum placental isoferritin values were significantly lower in the
second trimester of pregnancy in the gestational diabetes mellitus group (9.4+/
2.6 U/ml) as compared with the control group (21.5+/-2.2 U/ml, p=0.0001), and
were also significantly lower in the third trimester (3.7+/-1.9 vs. 19+/-2.6
U/ml, respectively, p=0.00001). CONCLUSIONS: Low serum PLF values detected in
gestational diabetes mellitus may reflect placental function and be related to
insulin treatment.
PMID- 9654172
TI - Interleukin-1alpha, interleukin-6 and interleukin-8 in cervico/vaginal secretion
for screening of preterm birth in twin gestation.
AB - BACKGROUND: The purpose was to determine the prognostic value of interleukin (IL)
1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (<37 weeks
of gestation) in twin pregnancies. METHODS: The study included screening of 121
women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of
gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The
detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal
fluid was smeared and dried for later evaluation of bacterial vaginosis (presence
of clue cells). RESULTS: Spontaneous preterm birth occurred in 36 women and 65
women were delivered at term. IL-8 was significantly higher (p=0.03) in samples
from women delivered preterm (median 3.72 ng/g mucus, range <0.07-220.00)
compared with samples from women delivered at term (median 3.03 ng/g mucus, range
<0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was
associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a
sensitivity, specificity, positive and negative predictive value of 78.8, 45.8,
44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not
significantly associated with preterm birth. Bacterial vaginosis was found in
47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were
significantly higher in samples positive for bacterial vaginosis than in negative
samples (p<0.0001 and p<0.01, respectively). There was no significant association
between the level of IL-6 and bacterial vaginosis. CONCLUSIONS: IL-8, but not IL
1alpha and IL-6, was associated with preterm delivery but the relationship was
too weak to be of predictive value for preterm birth in twin pregnancies. IL
1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.
PMID- 9654173
TI - The relationship between amniotic fluid interleukin-6 concentration and
histologic evidence of chorioamnionitis.
AB - BACKGROUND: Chorioamnionitis is considered to be one of the important causes of
preterm labor. To investigate the relationship between inflammatory cytokines in
amniotic fluid and the histologic evidence of chorioamnionitis, we studied
amniotic fluid interleukin-6 (IL-6) levels in patients with preterm labor.
METHODS: Between 1993 and 1996, we obtained amniotic fluid by amniocentesis from
110 patients before 32 weeks of gestation who had preterm labor on admission. We
measured IL-6 levels in the amniotic fluid with an ELISA method. Histologic
examination of placentae and fetal membranes after delivery was evaluated. As
controls, we measured IL-6 levels in the amniotic fluid of 37 patients without
preterm labor. Seventy-eight patients delivered after 35 weeks of gestation, and
32 patients delivered before 34 weeks of gestation. Analysis was conducted using
Mann-Whitney U test and Scheffe's multiple comparison test. RESULTS: Amniotic
fluid IL-6 levels in patients delivering before 34 weeks were significantly
higher than those in patients delivering after 35 weeks (p<0.01). IL-6 levels in
the amniotic fluid were significantly different among control patients, patients
without chorioamnionitis and those with histologic stages I, II and III which
means subchorionic intervillositis, chorionitis and amnionitis, respectively
(controls vs patients with stage I, II, III: p<0.001, patients without
chorioamnionitis vs those with stage II, III, stage I vs II, stage II vs III:
p<0.01). The IL-6 concentration in the amniotic fluid associated with histologic
stages II or III was above 3500 pg/ml (sensitivity: 87.5%, specificity: 89.5%).
CONCLUSIONS: Our findings indicate that amniotic fluid IL-6 may have a sensitive
diagnostic and prognostic value in the management of preterm labor and is an
index of the severity of chorioamnionitis during pregnancy.
PMID- 9654174
TI - A comparison of Caucasian and Southeast Asian Hmong uterine fundal height during
pregnancy.
AB - BACKGROUND: Fundal height measurement is a standard clinical assessment tool used
in prenatal care. This study compared the fundal heights growth curves of two
ethnically distinct groups of pregnant women. We were motivated by our clinical
experience with one group where fundal heights seemed 'small for date' and by the
reluctance of this group to undergo further testing, especially ultrasound.
METHODS: A prospective cohort study compared the fundal heights growth curve of
48 Caucasian and 40 Hmong women from two clinics in central Wisconsin (USA).
RESULTS: Southeast Asian Hmong women were found to have a slower rate of fundal
height growth than Caucasian women (significantly different average slopes of .88
vs. .95, respectively). An expectation of linear growth appeared more valid for
Caucasian than Hmong women. At 40 weeks, regression based estimates overestimated
the Caucasian sample by 1.3 weeks and the Hmong sample by 2.7 weeks. ANCOVA
procedures remained significant while controlling for group differences in
height. Fundal height measurements were moderately predictive of birth weight for
the Hmong sample but not the Caucasian sample (multiple r=.39). CONCLUSIONS:
Considerable differences emerged between fundal height measures for the Hmong and
Caucasian samples. The improved ability to differentiate groups following control
of variance due to height as well as the ability to predict birth weight from
fundal height curve in the Hmong group argue for value of normative development
using more homogeneous groups. Clinicians should consider the applicability of
fundal height norms to their clinical populations and may be able to have more
confidence in using fundal height as an evaluative tool with more appropriate
norms.
PMID- 9654175
TI - Impact of reverse end-diastolic flow velocity in umbilical artery on pregnancy
outcome after the 28th gestational week.
AB - BACKGROUND: The aim of this study was to discuss pregnancy outcome in
chromosomally and structurally normal fetuses having reverse end-diastolic flow
velocity (REDFV) on Doppler umbilical artery velocimetry (DUAV) in the third
trimester. METHODS: DUAV was performed in the high risk pregnancy antepartum
fetal surveillance. We excluded gestational age less than 28 weeks, multiple
pregnancies, and chromosomal or congenital anomalies. Thirty cases were
categorized as having REDFV The pregnancy outcome was investigated in these
cases. RESULTS: There were three stillbirths and 12 neonatal deaths, resulting in
a perinatal mortality rate of 50%. Twenty-eight patients (93.3%) had
complications with preeclampsia (20 of severe degree and eight moderate).
Cesarean section was performed on 24 patients (80%) due to acute fetal distress.
The mean gestational age at delivery was 31.8+/-3.2 weeks. The mean diagnosis-to
delivery interval was 10+/-8.2 hours. The average birth weight was 970+/-270 gm,
28 (93.3%) were found to be below the 10th percentile of ideal birth weight. An
umbilical artery pH less than 7.2 at delivery was found in 12 of 18 examined
cases (66.7%). Twelve out of 15 placentae (80%) showed significant infarcts on
pathological examination. All newborns (100%) needed admission to the neonatal
intensive care unit. CONCLUSIONS: REDFV on DUAV represents an ominous and severe
fetal condition with an adverse pregnancy outcome, especially in conditions
associated with preeclampsia and/or intrauterine growth retardation. Intensive
and frequent surveillance and aggressive management at the appropriate time would
improve perinatal outcome.
PMID- 9654176
TI - Pregnancy in HIV-infected women. Counseling and care--12 years' experiences and
results.
AB - BACKGROUND: A specialized antenatal care unit was set up for counseling and care
of HIV-infected pregnant women. The team consisted of gynecologists, a midwife, a
social worker and pediatricians. METHODS: The women were referred from
departments of infectious diseases, venereology or institutions for drug addicts,
antenatal care units and abortion clinics, or applied themselves. Women
identified in the pregnancy HIV screening program were informed primarily by the
team. The women were counseled along with their partners and cared for during
abortion or the antenatal period, delivery and post partum. Contraceptive
services were offered and psychosocial support was given. RESULTS: Between April
1985 and March 1997, 95 HIV-infected women with 122 pregnancies attended. Twenty
one per cent were or had been drug users, 2% had been infected by transfused
blood and 77% were classified as having been sexually infected, two thirds of
whom were Africans. The mean age was 27.8 years. In 54 of 93 pregnancies (58%) in
which the woman could make an informed decision, she elected abortion -- in 37
cases for HIV related reasons. Significantly more women with an uninfected steady
partner, compared to women without a steady partner, chose to continue the
pregnancy, as did women in a relatively stable social situation. Of the partners,
68 were HIV-negative, 36 HIV-positive and 18 not tested. No severe HIV-related
complications occurred during pregnancy. Seven of 40 (18%) children with a known
infection status were infected. During the course of follow-up, nine mothers, two
fathers and three children have died. Seventeen children were at risk of being
orphaned, and another five were placed in foster care. CONCLUSION: Although it is
possible to reduce mother-to-infant transmission by zidovudine therapy, the
negative consequences of HIV and childbearing are still substantial. Therefore
HIV screening during pregnancy and pre-pregnancy counseling are important issues
for the health care system.
PMID- 9654177
TI - Fear of childbirth during pregnancy may increase the risk of emergency cesarean
section.
AB - BACKGROUND: The purpose of our study was to elucidate the association between
fear of childbirth, general anxiety, and stress coping during the third trimester
of pregnancy, and a subsequent delivery by emergency cesarean section. METHODS:
In a case-control study, 1,981 Swedish-speaking women completed three self
assessment questionnaires at 32 weeks' gestation. Ninety-seven of these women
were delivered by emergency cesarean section. Fear of childbirth, general anxiety
and the stress coping ability of these 97 cases were compared with the same
features in 194 controls, matched for age and parity. RESULTS: Women,
subsequently delivered by emergency cesarean section, reported a greater anxiety
and a poorer stress coping ability, and, most obviously, a greater fear of
childbirth at 32 weeks' gestation. After elimination of possible confounders, the
odds ratio for emergency cesarean section was examined for women whose scores
were above various cut-off points according to the fear of childbirth measuring
instrument. For women with a serious fear of childbirth the odds ratio was 3.0
(95% confidence interval 1.4 to 6.6), and the population attributable risk 0.167.
CONCLUSION: Fear of childbirth during the third trimester of pregnancy may
increase the risk of subsequent emergency cesarean section.
PMID- 9654178
TI - Intrauterine irrigation with prostaglandin F2-alpha for management of severe
postpartum hemorrhage.
AB - BACKGROUND: Severe postpartum hemorrhage is a significant contributor to maternal
morbidity and mortality. The use of prostaglandin F2-alpha to control severe
postpartum hemorrhage may avert surgery for the control of bleeding. METHODS:
After ruling out the possibility of genital tract injuries, 18 patients with
severe postpartum hemorrhage caused by uterine atony were enrolled in the study.
None of the patients responded to treatment with oxytocin, methylergonovine, or
uterine massage. A Foley catheter was introduced into the uterine cavity and the
balloon was inflated with 5 ml sterile saline solution. The catheter was
connected to an infusion line of 500 ml saline solution containing 20 mg
prostaglandin F2-alpha. The solution was infused at a rate of 3-4 ml/minute for
the first 10 min, and then reduced to 1 ml/minute for a period of 12 24 hours.
RESULTS: In 17 patients (94.4%) bleeding ceased within several minutes of
initiation of intrauterine prostaglandin F2-alpha infusion, the uterus was firmly
contracted and uterine bleeding did not recur. In one patient with placenta
increta bleeding continued and hysterectomy was performed. None of the patients
had any side effects. CONCLUSIONS: Intrauterine irrigation with low
concentrations of prostaglandin F2-alpha is a simple, rapid and effective
treatment for severe postpartum hemorrhage and facilitates constant and
continuous hemostasis. Moreover, the minute dosage used eludes potentially
complicating side effects.
PMID- 9654179
TI - Premenstrual syndrome: comparison between different methods to diagnose cyclicity
using daily symptom ratings.
AB - BACKGROUND: In the diagnosis of premenstrual syndrome (PMS) the technique of
daily prospective symptom ratings is often used. Several methods of assessing
cyclicity, based on the daily prospective symptom ratings, have been presented in
the literature. In this paper we compare four different methods to assess
cyclicity. METHODS: Eighty consecutive patients seeking help for PMS at the
Department of Gynecology completed daily symptom ratings using a visual analogue
scale (VAS) during one menstrual cycle. They also made an Eysenck Personality
Inventory (EPI) and a thorough case history was taken regarding earlier
psychiatric case history. The methods compared were: a) the nonparametric Mann
Whitney U-test, b) effect size, c) Run-test and d) a 30% change in symptom degree
between the follicular and the luteal phase calculated in two different ways.
RESULTS: There was good agreement in the number of cyclic and non-cyclic patients
between the different diagnostic methods used with exception of the 30% of change
methods as the criteria for cyclicity. Here the number of non-cyclic patients
became higher and lower, respectively, than with the other methods. The
correlation between the number of symptoms for each patient showing cyclicity was
high in all tests. When comparing the median neuroticism score of the EPI-N
inventory the non-parametric, the Run-test and the effect size showed significant
differences between the non-cyclic group and the group of patients with pure PMS,
but not the 30%-change methods. Frequency of patients with psychiatric history
showed similar results. CONCLUSIONS: Three of the methods used seem to identify
the same patients as having or not having cyclical changes and probably also then
finding the same biological and/or psychological factor being responsible for the
cyclicity. There were, however, some differences in outcome of validity testing
and the 30%-change methods seem less valid than the other three methods. Due to
its simplicity and theoretical/statistical advances the Run-test seems most
preferable.
PMID- 9654180
TI - CO2 laser conization for cervical intraepithelial neoplasia grade II-III:
complications and efficacy.
AB - AIMS: To examine per- and postoperative complication rates and efficacy of laser
conization in the treatment of cervical intraepithelial neoplasia (CIN) grade II
III. MATERIAL AND METHODS: Eligible for analyses were all women treated with
their first laser conization because of CIN II-III during the time-period January
1, 1983 to December 31, 1992. The study population comprises 1081 women who were
permanent residents of one Norwegian county (Sor-Trondelag). All analyses were
performed in SPSS applying chi-square for trend, Mann-Whitney test, survival
analyses and logistic regression. RESULTS: In total 86 women (8.0%) were observed
with one or two (4:86) complications. Bleeding was most frequent (n = 66)
followed by symptomatic cervical stenosis (n = 18). Most bleeding complications
(74.2%) occurred one to two weeks postoperatively. Both bleeding complications
and the occurrence of cervical stenosis were associated with cone height. Three
emergency hysterectomies, two for bleeding and one for bladder perforation, were
performed. Persistent disease was diagnosed in 1.9% (20:1053) of the women. All
women with persistent disease were diagnosed among those with CIN III. Persistent
disease was more than 20 times more common among women with disease-involved
resection margins compared to those with free resection margins. CONCLUSIONS: Our
evaluation of ten years' consistent use of conization by CO2 laser in the
treatment of CIN II-III in an unselected population showed a low overall
complication rate (8%) and very high efficacy (CIN II 100%, CIN III 98.1%) of the
treatment.
PMID- 9654181
TI - Bleeding symptoms and subsequent risk of gynecological and other cancers.
AB - BACKGROUND: The purpose of our study was to find out whether bleeding symptoms
are predictive factors of subsequent gynecological or urinary cancers among women
screened negative. METHODS: The data stemmed from the Finnish Mass Screening
Registry, and were linked to the National Cancer Registry: 37,596 screening
negative women in the nationwide population-based mass screening program for
cervical cancer were classified by their bleeding symptom (bloody discharge,
coital bleeding, irregular bleeding, postmenopausal bleeding) at the time of
screening (1985-1990) and followed up (1985-1994) in order to assess the
subsequent risk of cancer. RESULTS: Bleeding symptoms with prevalence of 5.9%
were more likely to be signs of preinvasive than invasive cervical cancer with
the exception of coital bleeding, nevertheless relative risk of cervical cancer
(SIR 1.1, 95% CI 0.8-1.4) was not significantly increased during the total follow
up of maximum 10 years. Women with any bleeding symptom had increased risk of
cancer of the corpus uteri (SIR 2.1, 95% CI 1.6-2.6), postmenopausal bleeding was
the strongest symptom (RR 3.6, 95% CI 2.0-6.0). None of the bleeding symptoms
increased subsequent risk of ovarian, vaginal or vulvar carcinoma. The risk of
kidney cancer was increased (SIR 1.7, 95% CI 1.0-2.6). CONCLUSIONS: The
prevalence of bleeding symptoms was small and relative risks for cancers were low
for them to be suitable as predictive factors of cancer neither in clinical
practice nor for public health purposes, e.g. in developing selective screening
based on this high risk group. Only 34 gynecological cancers during 220,000
person-years in women with bleeding symptoms were attributable to bleeding.
Relative risks remained increased only for a short time after screening.
Therefore, short term surveillance is important, but due to the fact that
relative risks approached unity during the follow-up, reassurance of a woman that
she is cancer-free should be emphasized more in the long term after the bleeding
symptoms.
PMID- 9654182
TI - Exposure to angiotensin-converting enzyme inhibitors during first trimester: is
it safe to fetus?
PMID- 9654183
TI - Psychosocial factors in recurrent miscarriages.
PMID- 9654184
TI - Pregnancy in heart and heart-lung transplant recipients.
PMID- 9654185
TI - Management of a pregnancy complicated by the May-Hegglin anomaly.
PMID- 9654186
TI - Uterine arteriovenous malformation as a cause of immediate postpartum hemorrhage.
PMID- 9654187
TI - Hysteroscopic metroplasty under laparoscopic ultrasound guidance.
PMID- 9654188
TI - Stillbirths and rate of neonatal deaths in 76,761 postterm pregnancies in Sweden,
1982-1991; a register study.
PMID- 9654189
TI - Expression of membrane-type matrix metalloproteinase-1 in human pancreatic
adenocarcinomas.
AB - The expression of a new type of matrix metalloproteinase, membrane-type matrix
metalloproteinase-1 (MT-MMP-1), was examined in 24 cases of primary pancreatic
adenocarcinomas and 9 cases of secondary liver tumors derived from pancreatic
adenocarcinomas, using a non-radioactive in situ hybridization and
immunohistochemical methods. Out of 24 cases of primary pancreatic
adenocarcinomas, 18 showed positive expression of MT-MMP-1 transcripts in cancer
cells and 20 of 24 showed positive expression in the tumor stromal cells. The
immunoreactivity of the gene products for MT-MMP-1 was demonstrated to be almost
the same, as shown by in situ hybridization in these 24 cases. In particular,
both the staining intensity for MT-MMP-1 transcripts and the immunoreactivity of
the gene products in the tumor stromal cells of mucinous cystadenocarcinomas were
significantly weaker than those of common-type ductal adenocarcinomas among the
24 cases. All of the 9 cases of secondary liver tumors derived from pancreatic
adenocarcinomas showed positive expression for MT-MMP- transcripts but less
immunoreactivity for the gene products. These results suggest that MT-MMP-1 is
transcribed and translated in both cancer cells and the tumor stromal cells in
human pancreatic adenocarcinomas. Furthermore, considering that common-type
ductal adenocarcinoma of the pancreas usually shows a strong desmoplastic
reaction, while mucinous cystadenocarcinoma typically does not, MT-MMP-1
expressed in the tumor stromal cells of common-type adenocarcinomas may be
involved in processes leading to the desmoplastic reaction.
PMID- 9654190
TI - Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N
nitrosourea-induced tumor development in the urinary bladder of rats and to
mediate a local cellular immune response after long-term administration.
AB - Extracts from mistletoe (Viscum album L.) are assumed to exert an antineoplastic
activity through their toxicity at high doses or by immunomodulation by nanogram
quantities of a lectin. They are used as an unconventional therapy modality in
the management of a wide range of cancer diseases, although no anticancer
potential has yet been demonstrated. This prompted us to study the effect of
galactoside-specific lectin (VAA)--a major protein constituent of mistletoe with
immunomodulatory properties--on chemically induced tumor development in the
urinary bladder of rats and on the local cellular immune response after long-term
administration. To induce urothelial neoplasms N-methyl-N-nitrosourea (MNU) was
administered in a single intravesical dose (7.5 mg/kg body weight). Highly
purified VAA was given subcutaneously at its immunomodulatory dose (1 ng/kg body
weight) twice a week over the total experimental period of 15 months. The
incidences of epithelial bladder tumors were 25.0% following administration of
MNU alone and 22.9% in the rats additionally receiving VAA, which proved not to
be significantly different (P = 0.81). Quantitative immunohistochemistry
analyzing a panel of immune cell types, including T lymphocytes, T helper/inducer
cells (CD4), T suppressor/cytotoxic cells (CD8), T cells positive for interleukin
2 receptor (CD25), B lymphocytes and plasma cells, macrophages, natural killer
cells, granulocytes and all leukocytes expressing the leukocyte common antigen
(CD45), yielded no evidence for the ability of VAA to stimulate a substantial
cellular immunological reaction in the wall of the normal urinary bladder or
during urothelial carcinogenesis. In conclusion, the current experimental
findings provide no support at all that the galactoside-specific mistletoe lectin
is capable of inhibiting chemically induced bladder carcinogenesis and triggering
a local cellular immune response after prolonged application. It thus seems
highly improbable that commercial mistletoe preparations or VAA will be effective
in the management of human bladder cancer by a cell-mediated immunological
mechanism.
PMID- 9654191
TI - Chemoattractive effect on the effector cells of the supernatants from melanoma
cells transfected with the interleukin-2 (IL-2), IL-4 or IL-6 gene.
AB - By using the Boyden chamber system, the chemoattractive activity of the
supernatants from the B16 melanoma cells transfected with the interleukin-2 (IL
2), IL-4 or IL-6 gene was investigated. We found that supernatants from IL-2- or
IL-6-gene-transfected B16 melanoma cells showed chemoattractive activity on
natural killer (NK) cells, CD4+ T cells and CD8+ T cells, while the supernatants
from IL-4-gene-transfected B16 melanoma cells showed chemotactic activity on
macrophages but not on NK cells and T cells. Further, the chemoattractive
activity of the supernatants from cytokine-gene-transfected B16 cells might be
the direct effects of the cytokine that they have been engineered to secrete.
These results indicate that reduced tumorigenicity and increased immunogenicity
of cytokine-gene-transfected B16 cells may be attributed to the direct
recruitment of immune effector cells by the secreted cytokine, which plays an
important role in the induction of the local antitumor immunity.
PMID- 9654192
TI - Differentiation, proliferation and apoptosis levels in human leiomyoma and
leiomyosarcoma.
AB - A comparative analysis of the differentiation pattern, the proliferative
behaviour, and the level of apoptosis between human benign and malignant
neoplasms of smooth-muscle (SM) tissue is lacking. The clinical,
histopathological, immunochemical, and immunocytochemical features of leiomyomas
(LM) and leiomyosarcomas (LMS) were investigated by a panel of monoclonal
antibodies specific for some differentiation markers of SM tissue (SM myosin and
alpha-actin, desmin, and SM22) and for markers of non-muscle tissue (vimentin and
non-muscle myosin). Proliferating normal and neoplastic cells were identified by
proliferating-cell nuclear antigen (PCNA)/Ki67 immunostainings and the apoptotic
cells were revealed by means of the terminal-deoxynucleotidyltransferase-mediated
dUTP nick-end labelling technique. Gel electrophoresis and Western blotting,
performed with anti-(SM1/SM2 myosin isoform) antibody, indicated quantitative
differences between LMS and LM, which mirrored higher positive to negative
nuclear ratios for PCNA, Ki67 and apoptosis in malignant as opposed to benign
neoplasms. With LM, however, a similar SM1 to SM2 ratio could be associated with
different proliferation levels. Uterine, gastric and intestinal LMS displayed
specific patterns of SM1/SM2 and/or non-muscle myosin expression that were not
paralleled by different levels of proliferation/apoptosis. While the level of
PCNA/Ki67 correlated with the level of apoptosis in normal SM tissues and LM,
that of LMS did not. In vivo at the cellular level, LM and uterine LMS displayed
a near-uniform SM tissue differentiation, whereas the other LMS displayed a
lesser or a heterogeneous immunoreactivity. In vitro, cultured LMS cells showed a
limited and peculiar expression of SM myosin. In conclusion, there is no
reciprocal relationship between degree of differentiation and the level of
proliferation, as exemplified by the finding that the less differentiated
intestinal LMS displays the lowest proliferative behaviour and that the
relatively more differentiated gastric LMS/metastasis is more proliferative.
PMID- 9654194
TI - Impaired granulocytic function in patients with acute leukaemia: only partial
normalisation after successful remission-inducing treatment.
AB - In vivo chemotaxis and phagocytic activity of polymorphonuclear neutrophils (PMN)
were evaluated in 20 patients with acute myeloid leukaemia (AML), and in 10
patients with acute lymphoblastic leukaemia (ALL). For comparison, 20 healthy
individuals were investigated. A skin-chamber technique and a phagocytosis test
were used to quantify the neutrophil functions. The local leucocyte mobilisation
in the skin-chamber was significantly lower in untreated patients with AML and
ALL than in healthy individuals (P < 0.05). Patients with acute leukaemia in
remission showed an increase in chemotactic parameters though they remained below
normal levels. The phagocytosis index (PI) of peripheral blood PMN was lower than
30% (normal individuals: 60%) in untreated AML and ALL; this difference was
significant (P < 0.05). The PI of peripheral blood PMN in patients with acute
leukaemia in remission returned to the normal level. Investigation of
granulocytic function in patients with acute leukaemia in remission may reveal
evidence for reduced protection by these cells against infections and lead to
adequate therapy.
PMID- 9654193
TI - Does chemotherapy-induced leukopenia predict a response in small-cell lung
cancer?
AB - The correlation between chemotherapy-induced toxicity and treatment outcome in
cancer patients has not been studied thoroughly. Our aim was to evaluate whether
there is any relationship between chemotherapy-induced leukopenia and response to
treatment in small-cell lung cancer (SCLC). Data derived from records of 228
patients treated within two prospective multicentre phase II studies were
analysed. In the first study (101 patients) chemotherapy included vincristine,
epirubicin and cyclophosphamide and, in the second (127 patients),
cyclophosphamide, etoposide and epirubicin; both regimens were given every 3
weeks. In the present analysis, the correlation between treatment outcome
(response rate and survival) and highest scores of leukopenia within the first
two and up to the fourth chemotherapy cycle, respectively, was evaluated. The
objective response rate for the entire group was 66%; 53% in patients whose white
blood cells remained normal and 85% in those who developed leukopenia within the
first two cycles (P = 0.000). In multifactorial analysis, also including other
treatment- and patient-related factors, independent correlation with response to
chemotherapy was found for leukopenia (P = 0.001), chemotherapy regimen (P =
0.002) and the combined relative dose intensity (P = 0.018), but not for patient
sex, age, performance status, pre-study weight loss, extent of disease and
initial white blood cell count. Leukopenia within the first two cycles of
chemotherapy was not correlated with survival, whereas such correlation for
leukopenia occurring up to the fourth cycle was at the borderline level (P =
0.06). These findings suggest a relationship between chemotherapy-induced
leukopenia and tumour response in SCLC.
PMID- 9654195
TI - Increased prosomal proteins in breast cancer cells and in neighboring normal
cells in Parsi and non-Parsi populations.
AB - Monoclonal antibodies were raised against the prosomal proteins p27K, p29K and
the prosome-like protein p21K (PLP) from normal breast glandular cells and from
benign and malignant tumors. They were used to clarify the involvement of
prosomes in tumorigenesis of human breast cells. Immunostaining showed the
distribution of prosomes in the cytoplasm and nuclei of cells from European
normal women (EN) and Parsi (P) and non-Parsi (NP) benign (B) and malignant (M)
tissues. The flow-cytometry studies showed an increased mean percentage of
labeled cells, particularly with anti-p27K prosomal protein mAb, in malignant
tissue from NP compared to EN. The p21K data indicated an increase in the number
of cells labeled by flow-cytometry studies in all groups compared to EN, while
p29K-expressing cells were more abundant in NPN, PB, PM and NPM. Intergroup
comparison showed that the mean percentage of cells labeled with anti-p27K and
anti-p29K was significantly higher in PB than in NPB, as seen by flow cytometry,
whereas there was a higher production or accumulation of the p21K (PLP) prosomal
protein in NPM than in PM, as seen by immunostaining. By comparison with EN,
there were also significantly more normal cells containing the three antigens in
the apparently normal tissue in the neighborhood of the tumor in NPM, and more
cells containing p21K in PM patients than in EN. As prosomes are involved in the
cell differentiation and in the cell cycle control, the changes observed in
breast tissues may be related to oncogenic processes. Furthermore, the modified
subunit pattern of prosomes in cancer and, possibly, pre-cancer tissue may be of
interest for diagnosis purposes.
PMID- 9654196
TI - Complete response of a primary cutaneous T-cell-rich B cell lymphoma treated with
interferon alpha2a.
AB - Primary B cell lymphomas of the skin are rare disorders and therapy is not yet
standardized. A 45-year-old male patient presented 4 years after surgical removal
of a subcutaneous tumour of the leg. On examination a reddish nodular tumour was
found in the same region. The biopsy revealed a T-cell-rich primary B cell
lymphoma of the skin. Interferon alpha2a was given perilesionally at a dosage of
9 MU three times a week. The treatment was well tolerated, had no severe side
effects and induced a complete remission, both clinically and histologically,
during a 12-months course.
PMID- 9654197
TI - Correlation between Waardenburg syndrome phenotype and genotype in a population
of individuals with identified PAX3 mutations.
AB - Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized
by sensorineural hearing loss, pigmentary abnormalities of the eye, hair, and
skin, and dystopia canthorum. The phenotype is variable and affected individuals
may exhibit only one or a combination of several of the associated features. To
assess the relationship between phenotype and gene defect, clinical and genotype
data on 48 families (271 WS individuals) collected by members of the Waardenburg
Consortium were pooled. Forty-two unique mutations in the PAX3 gene, previously
identified in these families, were grouped in five mutation categories: amino
acid (AA) substitution in the paired domain, AA substitution in the homeodomain,
deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain and the Ser
Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are
based on the structure of the PAX3 gene and were chosen to group mutations
predicted to have similar defects in the gene product. Association between
mutation class and the presence of hearing loss, eye pigment abnormality, skin
hypopigmentation, or white forelock was evaluated using generalized estimating
equations, which allowed for incorporation of a correlation structure that
accounts for potential similarity among members of the same family. Odds for the
presence of eye pigment abnormality, white forelock, and skin hypopigmentation
were 2, 8, and 5 times greater, respectively, for individuals with deletions of
the homeodomain and the Pro-Ser-Thr-rich region compared to individuals with an
AA substitution in the homeodomain. Odds ratios that differ significantly from
1.0 for these traits may indicate that the gene products resulting from different
classes of mutations act differently in the expression of WS. Although a
suggestive association was detected for hearing loss with an odds ratio of 2.6
for AA substitution in the paired domain compared with AA substitution in the
homeodomain, this odds ratio did not differ significantly from 1.0.
PMID- 9654198
TI - A study of females with deletions of the short arm of the X chromosome.
AB - We have undertaken a clinical and molecular study of 25 females with deletions of
the short arm of the X chromosome. We have determined the deletion breakpoints,
the parental origin and the activation status of the deleted X chromosomes.
Genotype-phenotype correlations suggest that the presence of a single copy of the
DFFRX gene, previously postulated as a gene involved in the ovarian failure seen
in Turner syndrome, may be compatible with normal ovarian function, and that
there may be a gene for Turner-like features located in distal Xp22.3.
PMID- 9654199
TI - A haplotype and linkage disequilibrium analysis of the hereditary hemochromatosis
gene region.
AB - Hereditary hemochromatosis is a recessive disease of iron metabolism widely
distributed among people of European descent. Most patients have inherited the
causative mutation from a single ancestor. In the course of cloning the
hemochromatosis gene, genotypes were generated for these samples at 43
microsatellite repeat markers that span the 6.5-Mb hemochromatosis gene region.
The data used to reconstruct the ancestral haplotype across the hemochromatosis
gene region are presented in this paper. Portions of the ancestral haplotype were
present on 85% of patient chromosomes in this sample and ranged in size from
approximately 500 kb to greater than 6.5 Mb. Only one marker, D6S2239, was
identical by descent on all of the patient chromosomes containing the ancestral
mutation. In contrast, only 3 of the 128 control chromosomes, or 2.3%, carried
the ancestral mutation and the surrounding ancestral haplotype. To test new
methods for gene finding using linkage disequilibrium we analyzed the genotypic
data with a multilocus maximum likelihood method (DISMULT) and a single point
method (DISLAMB), both written to analyze data generated from multi-allelic
markers. The maximum value from DISLAMB analysis occurred at marker D6S2239,
which is less than 20 kb from the hemochromatosis gene HFE, consistent with the
haplotype analysis. The peak of the multi-point analysis was 700 kb from HFE,
possibly due to the nonuniform recombination rates within this large region. The
recombination rate appears to be lower than expected centromeric of the HFE gene.
PMID- 9654200
TI - Lack of association between human longevity and genetic polymorphisms in drug
metabolizing enzymes at the NAT2, GSTM1 and CYP2D6 loci.
AB - In the present study, the possible role of genetic polymorphism of three drug
metabolizing enzymes, debrisoquine/sparteine hydroxylase (CYP2D6), glutathione S
transferase mu (GSTM1), and N-acetyltransferase (NAT2), as a putative genetic
component of human longevity, was explored. A total of 817 DNA samples from a
centenarian and a control (20-70 years) population was subjected to PCR-coupled
RFLP methods. Subjects were genotyped for the CYP2D6*3 (A2637 deletion) and
CYP2D6*4 (G1934A transition) alleles, for four mutations of NAT2 [namely, NAT2*5A
(C481T), NAT2*6A (G590A), NAT2*7A (G857A), and NAT2*14A (G191A)], and for the
presence or absence of GSTM1 gene deletion. No significant difference was found
at these three loci between centenarian and control subjects with respect to
allelic variant frequencies, genotype distributions or predicted phenotypes
deduced from genotype combinations. By comparing the distribution of combined
genotypes for the polymorphisms tested at the CYP2D6, NAT2, and GSTM1 loci, none
of the predicted phenotypes concerning debrisoquine hydroxylase extensive
metabolizer or poor-metabolizer phenotypes, slow or fast N-acetylation
capacities, and active or defective glutathione S-transferase, could be
correlated with human longevity, alone or in combination.
PMID- 9654201
TI - Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the
structural gene DBH associate with biochemical phenotypic variation.
AB - Levels of the enzyme dopamine beta-hydroxylase (DbetaH) in the plasma and
cerebrospinal fluid (CSF) are closely related biochemical phenotypes. Both are
under strong genetic control. Linkage and association studies suggest the
structural gene encoding DbetaH (locus name, DBH) is a major locus influencing
plasma activity of DbetaH. This study examined relationships of DBH genotype
determined at two polymorphic sites (a previously described GT repeat, referred
to as the DBH STR and a single-base substitution at the 3' end of DBH exon 2,
named DBH*444 g/a), to CSF levels of DbetaH protein in European-American
schizophrenic patients, and to plasma DbetaH activity in European-American
patients with mood or anxiety disorders. We also investigated linkage
disequilibrium (LD) between the polymorphisms in the pooled samples from those
European-American subjects (n=104). Alleles of DBH*444 g/a were associated with
differences in mean values of CSF DbetaH levels. Alleles at both polymorphisms
were associated with plasma DbetaH activity. Significant LD was observed between
respective alleles with similar apparent influence on biochemical phenotype.
Thus, allele A3 of the DBH STR was in positive LD with DBH*444a, and both alleles
were associated with lower plasma DbetaH activity. DBH STR allele A4 was in
positive LD with DBH*444 g, and both alleles were associated with higher plasma
DbetaH activity. The results confirm that DBH is a major quantitative trait locus
for plasma DbetaH activity, and provide the first direct evidence that DBH also
influences CSF DbetaH levels. Both polymorphisms examined in this study appear to
be in LD with one or more functional polymorphisms that mediate the influence of
allelic variation at DBH on DbetaH biochemical phenotypic variation
PMID- 9654202
TI - Three splicing defects, an insertion, and two missense mutations responsible for
acute intermittent porphyria.
AB - Three splicing defects (IVS1+3G-->T, 86A-->T, IVS13-2A-->G), an insertion
(416insCA), and two missense mutations (664G-->A and 833T-->G) in the
porphobilinogen deaminase (PBGD) gene were identified in six unrelated Finnish
patients with acute intermittent porphyria (AIP). The IVS1+3G-->T substitution
resulted in activation of a cryptic splice site in intron 1 and retention of a 67
bp fragment in the mutant transcript. The 86A-->T mutation at the end of exon 3
was predicted to cause an amino acid substitution (E29L). However, sequencing of
the cDNA sample of the proband revealed exon 3 skipping from the mutant
transcript. The IVS13-2A-->G substitution caused retention of intron 13 in the
mutant transcript. In exon 8, 416insCA resulted in a frameshift. All three
splicing defects and the CA insertion resulted in a truncated protein and thus,
probably the loss of PBGD activity. The two novel missense mutations, 664G-->A in
exon 12 and 833T-->C in exon 14 caused a single amino acid substitution (V222M
and L278P). So far 25 different mutations have been characterized from 37 (93%)
of a total of 40 unrelated Finnish AIP families, confirming the genetic
heterogeneity of the disease even in a previously isolated area of Finland.
PMID- 9654203
TI - High throughput fluorescence-based conformation-sensitive gel electrophoresis (F
CSGE) identifies six unique BRCA2 mutations and an overall low incidence of BRCA2
mutations in high-risk BRCA1-negative breast cancer families.
AB - Mutational analysis of cancer susceptibility genes has opened up a new era in
clinical genetics. In this report we present the results of mutational analysis
of the BRCA2 coding sequences in 105 high-risk individuals affected with breast
cancer and/or ovarian cancer and previously found to be negative for mutations of
the BRCA1 coding sequence in our laboratory. These individuals have a positive
family history with three or more cases of breast cancer and/or ovarian cancer at
any age from the same side of the family tree. In order to perform a high
throughput and reliable mutational analysis of the BRCA genes, we have adapted
the conformation-sensitive gel electrophoresis mutation-scanning assay to a
fluorescent platform. The advantages are speed, reproducibility and enhanced
resolving power of the scanning method. Four unique mutations, including one
missense and three frameshift mutations, were identified in the pool of 60 non
Jewish patients (7%). Two cases of the 6174delT mutation were identified in the
45 Ashkenazi Jewish individuals studied (5%). In addition, two novel frameshift
mutations, not characteristic of the Jewish subgroup, were identified. Thus there
were four mutations in total in this ethnic subgroup (9%). The six mutations
identified in this combined patient pool, excluding the 6174delT mutations, are
novel and have not been previously reported in the Breast Cancer Information Core
(BIC) database. The results indicate that BRCA2 mutations account for the disease
in less than 10% of this patient population. In addition, there is no significant
difference in frequency of BRCA2 mutations between the Ashkenazi Jewish and non
Jewish families in our clinical patient pool.
PMID- 9654204
TI - Deletion mapping by FISH with BACs in patients with partial monosomy 22q13.
AB - Patients with deletions in 22q13 are known to have phenotypic features that
include normal or accelerated growth, large hands and feet, hypotonia, delayed
psychomotor development and mild facial dysmorphism. To date, very few cases have
been investigated by detailed molecular genetic analysis. We have analyzed three
new patients with terminal deletions in 22q. We compared the cytogenetic
observations with molecular data assessed by fluorescence in situ hybridization
and an array of characterized bacterial artificial chromosome recombinants. The
shortest region of deletion overlap is localized in 22q13.2-qter distal to the
marker D22S94, but the telomeric repeat in the deleted chromosome appears to
remain intact. When parental alleles were investigated in two of the three
patients, the aberrant homolog was found to be of paternal origin in both cases.
Although the deleted region still spans >20 cM, molecular analysis of additional
patients and screening for new genes might help in elucidating candidate genes
connected with the dysmorphisms defined by deletions of 22q13.
PMID- 9654205
TI - LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias.
AB - A group of 30 Polish families with clinical signs of familial
hypercholesterolemia was studied for the presence of germ-line mutations in the
LDL-R and ApoB-100 genes. Screening of the LDL-R gene was performed at the
genomic DNA level by single-strand conformation polymorphism analysis of all 18
exons and extended by sequencing of polymerase chain reaction (PCR) products
showing abnormalities. The occurrence of large LDL-R gene alterations was
evaluated by analysis of restriction enzyme patterns on Southern blots and using
the long-PCR technique. The ApoB-100 gene was studied by combined allele-specific
and asymmetric PCR for the occurrence of the common B-3500 missense mutation G to
A at nucleotide position 10,708. Germ-line mutations were found in 17 families.
In 12 of them LDL-R gene mutations were detected. Three of 11 different mutations
had previously been described in other populations (3-bp deletion of codon 197;
Ser156Leu; Gly571Glu). Of the mutations not previously recognized and identified
in Polish families, there were three small deletions (2-bp deletion AG at codon
291; 4-bp deletion CCCT at codons 661-662; 1-bp deletion A at codon 830), and
four point mutations (Arg239Stop, Cys331Stop, Asn543Ser, Gln665Stop).
Additionally, one large (approximately 1-kb) LDL-R gene deletion between exons 6
and 9 was identified. In five families, the B-3500 mutation within the ApoB-100
gene was revealed.
PMID- 9654206
TI - A quarter of men with idiopathic oligo-azoospermia display chromosomal
abnormalities and microdeletions of different types in interval 6 of Yq11.
AB - Cytogenetic investigations and molecular analysis of the Y chromosome by the
polymerase chain reaction amplification of sequence-tagged sites (STS-PCR)
technique were performed in 126 patients affected by idiopathic oligo-azoospermia
following accurate selection of cases. Seventeen patients evidenced an abnormal
karyotype. Fourteen patients with a normal karyotype had microdeletions of the Y
chromosome within interval 6. In azoospermic patients microdeletions were
scattered along different subintervals, while in oligozoospermic patients they
were clustered in subinterval 6E. The size of the deletion was not apparently
related to the severity of the disease. These results suggest that cytogenetic
analysis and the STS-PCR technique can detect a genetic cause of infertility in
about one-quarter of patients with idiopathic oligo-azoospermia.
PMID- 9654207
TI - Partial biotinidase deficiency is usually due to the D444H mutation in the
biotinidase gene.
AB - Newborn screening for biotinidase deficiency has identified children with
profound biotinidase deficiency (<10% of mean normal serum activity) and those
with partial biotinidase deficiency (10%-30% of mean normal serum activity).
Children with partial biotinidase deficiency and who are not treated with biotin
do not usually exhibit symptoms unless they are stressed (i.e., prolonged
infection). We found that 18 of 19 randomly selected individuals with partial
deficiency have the transversion missense mutation G1330>C, which substitutes a
histidine for aspartic acid444 (D444H) in one allele of the biotinidase gene. We
have previously estimated that the D444H mutation results in 48% of normal enzyme
activity for that allele and occurs with an estimated frequency of 0.039 in the
general population. The D444H mutation in biotinidase deficiency is similar to
the Duarte variant in galactosemia. The D444H mutation in one allele in
combination with a mutation for profound deficiency in the other allele is the
common cause of partial biotinidase deficiency.
PMID- 9654208
TI - Structural organisation of the gene encoding the alpha-subunit of the human
amiloride-sensitive epithelial sodium channel.
AB - The human amiloride-sensitive epithelial sodium channel (ENaC) is a member of the
degenerin/ENaC family of ion channels and regulates fluid and electrolyte
absorption across a number of epithelia, including kidney, colon and lung. Native
ENaC has been shown to be a multimer made up of at least three homologous
subunits (alpha, beta, gamma) and mutations affecting the channel complex have
been identified in various human diseases. "Gain of function" mutations in one of
the three ENaC subunits have been found to cause pseudoaldosteronism (Liddle's
syndrome) and ENaC "reduction of function" mutations are found in patients
affected with the recessive form of pseudohypoaldosteronism (PHA) type 1. In this
report, we describe the genomic organisation of the human alphaENaC gene. Human
alphaENaC consists of 13 exons spanning 17 kb on chromosome 12p13 and contains at
least eight Alu sequences. In addition to the intron/exon boundaries, we have
deciphered almost all the intron sequences and 475 bp of the CCAAT-less and TATA
less 5' flanking region.
PMID- 9654209
TI - Cystic-fibrosis-like disease unrelated to the cystic fibrosis transmembrane
conductance regulator.
AB - Cystic fibrosis (CF) is considered to be a monogenic disease caused by molecular
lesions within the cystic fibrosis transmembrane conductance regulator (CFTR)
gene and is diagnosed by elevated sweat electrolytes. We have investigated the
clinical manifestations of cystic fibrosis, CFTR genetics and electrophysiology
in a sibpair in which the brother is being treated as having CF, whereas his
sister is asymptomatic. The diagnosis of CF in the index patient is based on
highly elevated sweat electrolytes in the presence of CF-related pulmonary
symptoms. The investigation of chloride conductance in respiratory and intestinal
tissue by nasal potential difference and intestinal current measurements,
respectively, provides no evidence for CFTR dysfunction in the siblings who share
the same CFTR alleles. No molecular lesion has been identified in the CFTR gene
of the brother. Findings in the investigated sibpair point to the existence of a
CF-like disease with a positive sweat test without CFTR being affected. Other
factors influencing sodium or chloride transport are likely to be the cause of
the symptoms in the patient described.
PMID- 9654210
TI - Relative frequencies of cystic fibrosis mutations in The Netherlands as an
illustration of significant regional variation in a small country.
AB - Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in
white populations. Significant regional differences in CF mutations among
affected individuals have been reported. We have studied the geographic
distribution of the relative frequencies of the three most common Dutch CF
mutations, deltaF508, A455E, and G542X, by analyzing data on area of residence of
CF patients. Significantly higher relative frequencies of the A455E mutation and
the G542X mutation were observed in the South-West and the South-East,
respectively. A uniform distribution of relative frequencies was found for the
deltaF508 mutation. The results of our study show that, even in a small country
such as The Netherlands, certain CF mutations may be more common in one region
than in another.
PMID- 9654211
TI - Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of
maternal origin and commonly associated with a learning disability, dysmorphic
features and developmental delay.
AB - Mutation screening in neurofibromatosis type 1 (NF1) families has long been
hampered by the complexity of the NF1 gene. By using a novel multi-track
screening strategy, 67 NF1 families (54 two-generation, 13 three-generation) with
a de novo mutation in the germline of the first generation were studied with two
extragenic and 11 intragenic markers. The pathological lesion was identified in
31 cases. Loss of heterozygosity (LOH) in the affected individual revealed a
gross gene deletion in 15 of the two-generation families; in 12 (80%) of them,
the deletion was maternally derived. Eleven patients with a gross deletion
exhibited developmental delay, ten had dysmorphic features and six manifested a
learning disability. No gross deletion was apparent in any of the 13 three
generation families, suggesting that such lesions are subject to more intense
selection. In these families, the new mutation was of paternal origin in 11
kindreds and the underlying mutational event could be characterised in three of
them.
PMID- 9654212
TI - The effects of splice site mutations in patients with naevoid basal cell
carcinoma syndrome.
AB - We have previously identified the human homologue of the Drosophila patched gene
and have described, in this gene, mutations that give rise to naevoid basal cell
carcinoma syndrome (NBCCS). Here, we have analysed the effects of three splice
site mutations within human PATCHED (PTCH) by the reverse
transcription/polymerase chain reaction method in cultured patient lymphocyte
cell lines. Two alterations, a point mutation in intron 7 and an insertion in
intron 10, lead to premature truncation of the PATCHED protein. Another point
mutation in intron 17 results in the skipping of exon 18 and the subsequent in
frame deletion of 46 amino acids. Additionally, in all lymphocyte and
keratinocyte cell lines examined, exon 10 of PTCH is alternatively spliced
leading to an in-frame deletion of 52 amino acids.
PMID- 9654214
TI - Respiratory depression produced by intravenously administered NBQX.
AB - To determine whether blockade of non-N-methyl-D-aspartate (non-NMDA) excitatory
amino acid receptors affects breathing, we administered the non-NMDA receptor
antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), to
anesthetized cats while monitoring phrenic nerve discharge, blood pressure and
heart rate. NBQX, 3 and 10 mg/kg, i.v., reduced phrenic amplitude 59 +/- 20% (n =
3) and 88 +/- 6% (n = 5), respectively, and decreased respiratory rate. Phrenic
activity was completely silenced in 3 animals. These effects were accompanied by
decreased blood pressure and heart rate. Our data indicate that NBQX, a
competitive antagonist of non-NMDA receptors, is a powerful depressant of
cardiorespiratory activity.
PMID- 9654213
TI - The contractile effect of fedotozine on guinea pig isolated intestinal cells is
not mediated by kappa opioid receptors.
AB - The compound fedotozine, recently described as a peripheral kappa opioid receptor
agonist, was tested on smooth muscle cells isolated from the longitudinal muscle
layer of the guinea pig ileum, in comparison with the selective kappa receptor
agonist, compound U-50488. Fedotozine (1 nmol/l-1 micromol/l) caused a
concentration-dependent contraction of intestinal cells, with a maximum decrease
in cell length not significantly different from that caused by acetylcholine. The
kappa agonist U-50488 (0.1 pmol/l-100 nmol/l) was without effect. The contractile
effect of fedotozine was not significantly modified by naloxone (0.1-1
micromol/l). These results indicate that fedotozine can have direct excitatory
effects on intestinal smooth muscle cells from the guinea pig ileum not mediated
by activation of kappa opioid receptors.
PMID- 9654215
TI - Acute natriuretic effect of fasidotrilat, a mixed inhibitor of neutral
endopeptidase and angiotensin I-converting enzyme, in rats with heart failure.
AB - The acute diuretic and natriuretic effects of fasidotrilat, a mixed inhibitor of
neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE) were
evaluated in control and myocardial-infarcted rats. Fasidotrilat injection (10
mg/kg i.v.) had no significant effect on arterial blood pressure and led to
significant elevations in urine volume (+57% in control rats and +114% in
infarcted rats) and of urinary sodium excretion (+81% in control rats and +225%
in infarcted rats). Comparison between control and infarcted rats showed that
fasidotrilat-induced changes in diuresis and natriuresis were higher in infarcted
rats (2.4-fold for diuresis and 4.7-fold for natriuresis, p < 0.05), despite a
lower perfusion pressure (-10 mm Hg) in infarcted rats. These data show the
potential therapeutic interest of mixed NEP/ACE inhibitors in congestive heart
failure.
PMID- 9654216
TI - Pharmacokinetics and pharmacodynamics of mibefradil in hypertensive patients with
varying degrees of renal insufficiency.
AB - Mibefradil, the first member of the tetralol derivatives, a new class of calcium
antagonists, is used for the treatment of hypertension and angina pectoris. This
study was designed to investigate the effect of varying degrees of chronic renal
impairment on mibefradil pharmacokinetics and pharmacodynamics. Neither
pharmacokinetic nor pharmacodynamic parameters varied as a function of renal
status. Additionally, hemodialysis removed only a relatively small fraction of
drug from the body. It was concluded that the majority of renal-failure patients
will not require a change in mibefradil dosage relative to patients with normal
renal function. Following hemodialysis, supplemental mibefradil treatment should
not be necessary.
PMID- 9654217
TI - Effects of ketoconazole on digoxin absorption and disposition in rat.
AB - Digoxin, a cardiac glycoside, is a substrate of the multidrug transporter P
glycoprotein (Pgp), and in rats has also been identified as a substrate for
cytochrome P450 3A (CYP3A). Ketoconazole, an antifungal agent, was shown to
inhibit Pgp in a multidrug-resistant cell line, and is known to be a potent
inhibitor of CYP3A. Here, we determined the effects of ketoconazole on digoxin
absorption and disposition in rats. Digoxin was administered intravenously or
orally with or without a concomitant oral dose of ketoconazole. When given
intravenously, digoxin AUC increased from 93 +/- 22 to 486 +/- 26 microg x h/l
with ketoconazole administration. Similarly, ketoconazole raised the AUC of
orally administered digoxin from 63 +/- 17 to 411 +/- 50 microg x h/l.
Concomitant ketoconazole administration prolonged digoxin elimination, yielding a
nonlinear pharmacokinetic profile. Using time-averaged values, digoxin
bioavailability increased from 0.68 +/- 0.18 to 0.84 +/- 0.10, while mean
absorption time was reduced from 1.1 +/- 0.4 to 0.3 +/- 0.1 h. Thus, in rats,
ketoconazole increases digoxin plasma concentrations, rate of absorption and
bioavailability. Although the effects of ketoconazole on AUC could be explained
by inhibition of both CYP3A and Pgp, which cannot be differentiated in this
study, the decreased mean absorption time can only be explained by inhibition of
Pgp in the intestine.
PMID- 9654218
TI - A method for measuring naringenin in biological fluids and its disposition from
grapefruit juice by man.
AB - The major flavonoid in grapefruit juice, naringin, has an aglycone, naringenin,
that inhibits some oxidations in vitro and may have in vivo activity. We
developed an HPLC method to measure naringenin using a methanol:water mobile
phase with UV absorbance detection. The recovery of naringenin was 96%. Two
subjects who drank grapefruit juice containing 214 mg naringin daily excreted
approximately 30 mg/day of naringenin glucuronide. Thus, naringin is hydrolyzed
to naringenin and then conjugated with glucuronic acid prior to excretion of the
conjugate.
PMID- 9654219
TI - Predictive sensitivity of human cancer cells in vivo using semipermeable
polysulfone fibers.
AB - An in vivo experimental model was developed to predict efficiently and accurately
chemosensitivity of human tumors. Human cancer cells either from cultured cell
lines or from patients' tumors were injected directly into semipermeable
polysulfone fibers subsequently implanted into immunocompetent rats. Results
suggest utility of this novel model system for predicting tumor sensitivity to a
wide range of anticancer agents and for potentially guiding the treatment of
cancer patients in the clinical setting.
PMID- 9654220
TI - Preserved autonomic modulation of the sinus and atrioventricular nodes following
posteroseptal ablation for treatment of atrioventricular nodal reentrant
tachycardia.
AB - INTRODUCTION: Following radiofrequency catheter ablation of AV nodal reentrant
tachycardia (AVNRT), inappropriate sinus tachycardia may occur, possibly due to
damage to autonomic cardiac nerve fibers. Furthermore, inducibility of AVNRT is
often critically dependent on the autonomic balance. We investigated whether
successful ablation of AVNRT is associated with an alteration of autonomic input
to the sinus and AV nodes. METHODS AND RESULTS: To estimate changes in the
autonomic modulation of the sinus and AV nodes, power spectra of beat-to-beat PP
and PR intervals were analyzed from high-quality nighttime ECG recordings of 11
patients before and after radiofrequency application. Normalized HF power (nHF)
of PP and PR intervals was used as an index of efferent vagal modulation and the
LF/HF ratio as an index of sympathovagal balance of the sinus node (PP) and AV
node (PR). Before ablation, LF/HF(PP) was 3.2 and nHF(PP) was 0.3 in the sinus
node. For the AV node, LF/HF(PR) was 1.2 and nHF(PR) was 0.5. Following ablation,
LF/HF(PP) (3.5) and nHF(PP) (0.3) of the PP intervals did not change. Similarly
to the sinus node, there were no changes in the autonomic modulation of the AV
node, as both LF/HF(PR) (1.2) and nHF(PR) (0.5) remained unchanged. CONCLUSION:
Our results indicate that autonomic control of the sinus and AV nodes is
preserved following successful radiofrequency ablation of AVNRT. The effects of
posteroseptal radiofrequency current application are not necessarily mediated by
changes in the autonomic input to the AV node.
PMID- 9654221
TI - Lack of benefit of very short basic drive train cycle length or repetition of
extrastimulus coupling intervals for induction of ventricular tachycardia.
AB - INTRODUCTION: There are considerable variations of uncertain importance in basic
drive train cycle lengths and degree of repetition of extrastimuli used in
programmed ventricular stimulation protocols in different laboratories. We
compare prospectively three different stimulation protocols to examine the
influence of a short basic drive train cycle length and repetition of
extrastimuli on induction of ventricular tachycardia. METHODS AND RESULTS: Thirty
consecutive patients who had documented ventricular tachycardia or fibrillation
based on underlying coronary artery disease underwent programmed ventricular
stimulation with each of the three study protocols. Protocol A used a basic drive
train cycle length of 400 msec with each extrastimulus coupling interval
delivered only once. Protocol B used the same basic drive train cycle length, but
with each extrastimulus coupling interval repeated three times before
decrementing. Protocol C used 300 msec as the cycle length of basic drive trains
without repetition of extrastimuli. Sixty-three percent, 67%, and 63% of the
study patients had ventricular tachycardia inducible with protocols A, B, and C,
respectively (P = NS). Ventricular fibrillation was induced in 23% of the 30
patients in all three protocols. There were no significant differences in the
mean cycle lengths of induced ventricular tachycardia, the number of extrastimuli
used, and the coupling interval of the last extrastimulus inducing ventricular
tachycardia among the three protocols. CONCLUSION: This study showed no clinical
benefit for repetition of extrastimuli that have failed to induce a ventricular
tachyarrhythmia during programmed ventricular stimulation. A short basic cycle
length of 300 msec was not superior to 400 msec for induction of ventricular
tachyarrhythmias. We recommend the use of basic cycle length 400 msec with
delivery of each extrastimulus interval only once as the initial protocol for
programmed ventricular stimulation.
PMID- 9654222
TI - Effect of electrode length on atrial defibrillation thresholds.
AB - INTRODUCTION: Catheter-based electrodes have been used previously to terminate
episodes of atrial fibrillation in animals and man. Typically, these electrodes
span 6 to 7 cm, and lowest energy requirements are achieved when these electrodes
are positioned in the distal coronary sinus and in the right atrium. The purpose
of this study was to evaluate the use of longer electrode lengths for atrial
defibrillation. METHODS AND RESULTS: In 15 patients, two decapolar catheters were
inserted, one into the distal coronary sinus and one in the right atrium. To
provide longer electrodes lengths, a third catheter was inserted and alternated
positioned in the right atrium or coronary sinus. A 6-cm electrode span was
obtained by using the distal 8 rings on the coronary sinus catheter or 8
consecutive electrodes on the right atrial catheter and increased from 6 to 11 cm
by connecting 5 consecutive, nonoverlapping rings of the third catheter with the
10 rings of the initial right atrial or coronary sinus catheter. Atrial
defibrillation thresholds were determined twice, in a randomized order, in each
patient for each of the three combinations of electrode lengths. All 15 patients
could be successfully converted to sinus rhythm without complications; however,
one patient could be converted reproducibly with only 2 of the 3 electrode
combinations. Mean thresholds were 306 +/- 102 V, 5.9 +/- 4.0 J for the 6 cm/6 cm
electrode length combination with an impedance of 72 +/- 18 omega. For the
electrode combination using the 11-cm electrode in the right atrium, the
defibrillation threshold was 296 +/- 107 V, 5.8 +/- 3.9 J with an impedance of 61
+/- 17 omega and was 294 +/- 91 V, 5.6 +/- 3.6 J with an impedance of 55 +/- 11
omega for the 11-cm electrode in the coronary sinus. There were no significant
differences in defibrillation voltage or energy (P > 0.05) associated with the
longer electrode lengths; however, the longer electrode lengths did significantly
lower shock impedance (P < 0.05). CONCLUSION: The use of longer electrodes, when
using the right atrium to coronary sinus shock vector, does not lower the
defibrillation requirements for restoration of sinus rhythm.
PMID- 9654223
TI - Immediate reproducibility of upper limit of vulnerability measurements in
patients undergoing transvenous implantable cardioverter defibrillator
implantation.
AB - INTRODUCTION: Measurement of the upper limit of vulnerability (ULV) with
monophasic T wave shocks has been proposed as a patient-specific measurement of
defibrillation efficacy that results in fewer episodes of ventricular
fibrillation (VF) than measurement of a defibrillation efficacy curve. METHODS
AND RESULTS: We sought to determine the magnitude of variance in ULV in 63
consecutive patients undergoing implantation of an implantable cardioverter
defibrillator (ICD). We measured ULV as the strength at or above which VF is not
induced when a stimulus is delivered at 310 msec after an 8-beat ventricular
pacing drive at 400 msec. Defibrillation threshold (DFT) was measured in patients
with an active can device using a biphasic waveform and the binary search method
beginning at 12 J. Sixty-three patients were studied; they had a mean age of 62
+/- 12 years and a mean ejection fraction of 35% +/- 15%. Three quarters of
patients had an ischemic cardiomyopathy. Each patient underwent 4.5 +/- 0.8
measurements of ULV. Monophasic ULV correlated poorly with biphasic DFT (R
between 0.19 and 0.28, P = 0.04 to 0.17). There was no change in ULV between
second to third, third to fourth, and first to last measurement in 22% to 41% of
patients. The reliability coefficient was 0.87. A ULV > or = 20 J was found in
eight patients. The only predictor of high ULV was a high DFT. CONCLUSION:
Monophasic ULVs do not closely predict biphasic active can DFTs using a standard
protocol. High DFTs were predicted by high ULVs. There was little variation in
the acute measurement of ULV between trials. These findings have important
implications for using ULV measurements to determine changes in DFTs after
interventions. The methodology of determining ULV is critical to its use for
predicting DFTs and programming ICDs.
PMID- 9654224
TI - Altered pattern of connexin40 distribution in persistent atrial fibrillation in
the goat.
AB - INTRODUCTION: Since altered expression of gap junction proteins (connexins) in
diseased myocardial tissue may lead to abnormal electrical coupling between
cardiomyocytes and hence contribute to arrhythmogenesis, the expression of
connexin(Cx)40 and Cx43 was studied in atrial appendage from goats in sinus
rhythm (SR) and persistent atrial fibrillation (AF). METHODS AND RESULTS:
Biopsies were taken from the left and right atrial appendages from goats in SR or
after pacing-induced persistent AF. Analyses of Cx40 and Cx43 mRNA and protein
levels, using quantitative (competitive) polymerase chain reaction and western
blotting, respectively, revealed no significant changes in the overall expression
of Cx40 and Cx43 as a result of persistent AF. At the cellular level,
immunohistochemistry and confocal laser scanning microscopy showed a homogeneous
distribution of either connexin in atrial sections taken during SR. After
induction of AF, the distribution of Cx43 gap junctions was unchanged whereas the
Cx40 pattern showed marked inhomogeneities with small areas (0.15 to 0.6 mm in
diameter, 25% of section surface area) of low-density Cx40 located between larger
areas of normal (unchanged) Cx40 density. Activation mapping (244 electrodes,
spatial resolution 2.25 mm) of the right atrial wall did not reveal changes in
atrial conduction velocity. CONCLUSION: Pacing-induced persistent AF in the goat
gave rise to changes in the spatial organization of Cx40 gap junctions. Although
the overall conduction velocity appeared not to have changed,
microheterogeneities in conduction due to the local redistribution of Cx40 gap
junctions might have contributed to the initiation and maintenance of AF.
PMID- 9654225
TI - Connexins, conduction, and atrial fibrillation.
PMID- 9654226
TI - Antibodies against myosin in sera of patients with idiopathic paroxysmal atrial
fibrillation.
AB - INTRODUCTION: Circulating autoantibodies against myosin heavy chain have been
detected in patients with ventricular myocarditis and in patients with dilated
cardiomyopathy. This study investigated the presence of antibodies against myosin
in sera of healthy control persons as compared with patients with idiopathic
paroxysmal atrial fibrillation refractory to antiarrhythmic therapy. METHODS AND
RESULTS: An SDS-PAGE (sodium dodecylsulfate polyacrylamide gel electrophoresis)
procedure, followed by Western blotting with homogenates and membrane fractions
of human left ventricular and atrial specimen as antigens, was used to analyze
sera of 10 patients with idiopathic paroxysmal atrial fibrillation and 10 age
matched healthy control subjects. Circulating immunoglobulin G reactivity against
cardiac myosin heavy chain was detected in 6 patients (60%) as compared with 1
control subject (10%). This difference was statistically significant (P < 0.05).
All patients with idiopathic paroxysmal atrial fibrillation who showed reactivity
against myosin heavy chain also had specific reactivity in their sera that
exhibited reactivities to both ventricular and atrial cardiac myosin heavy chain
isoforms. CONCLUSION: This study demonstrates the presence of circulating
autoantibodies against myosin heavy chain in a significant percentage of patients
with idiopathic paroxysmal atrial fibrillation and raises the possibility of an
autoimmune process in some patients with paroxysmal atrial fibrillation.
PMID- 9654227
TI - Lone atrial fibrillation and autoantibodies: cause versus effect.
PMID- 9654228
TI - Novel donor splice site mutation in the KVLQT1 gene is associated with long QT
syndrome.
AB - INTRODUCTION: Inherited long QT syndrome (LQTS) recently has been associated with
mutations in genes coding for potassium (KVLQT1, KCNE1, and HERG) or sodium
(SCN5A) ion channels involved in regulating either sodium inward or potassium
outward currents of heart cells, resulting in prolongation of the repolarization
period. We describe a new mutation, a -1 donor splice site mutation in a kindred
with two affected members (QTc = 0.61 and 0.54 sec). METHODS AND RESULTS: Single
stranded conformation polymorphism (SSCP) analyses were performed on DNA
fragments amplified by polymerase chain reaction from DNA extracted from whole
blood. Aberrant conformers were analyzed by DNA sequencing. SSCP analysis of the
KVLQT1 gene revealed an aberrant conformer in the affected family members. DNA
sequencing confirmed the presence of a G-->A change in the last nucleotide of
codon 344. This mutation does not cause an amino acid change, but a change of the
splice site characteristics at the 3' end of exon 6. The mutation may affect,
through deficient splicing, the putative sixth transmembrane segment of the K+
channel, and this type of mutation has not previously been described in KVLQT1.
CONCLUSION: The clinical course of LQTS in the affected family members, in whom
no deaths occurred despite 20 to 30 syncopes, can be explained by the ability of
the cellular machinery to perform partial correct splicing in the mutant allele.
This type of mutation may be misinterpreted as a normal variant, since it is a
point mutation causing neither an amino acid change nor the introduction of a
stop codon.
PMID- 9654229
TI - Nonfluoroscopic transseptal catheterization: safety and efficacy of intracardiac
echocardiographic guidance.
AB - INTRODUCTION: Recently, there has been a revival in the use of transseptal
catheterization due to the development of balloon mitral valvuloplasty and
radiofrequency catheter ablation. Complications of transseptal puncture, although
rare, can be serious and life-threatening. In the present study, we evaluated the
use of intracardiac echocardiography (ICE) as the sole imaging modality to guide
transseptal puncture and catheterization. METHODS AND RESULTS: In each animal, 10
transseptal punctures were performed guided solely by ICE. The standard approach
to transseptal catheterization using a Brockenbrough needle and long vascular
sheath was used except for the use of ICE instead of fluoroscopy. A 6.2
French/12.5-MHz and 9-French/9-MHz ICE catheter was used for imaging. At the end
of each study, pathologic evaluation was performed. Transseptal puncture was
performed safely, guided solely by ICE, in each of 100 attempts (five attempts
guided by each ICE catheter in 10 dogs). While the fossa ovalis was easily
visualized with both ICE catheters, the 9-French/9-MHz catheter offered an
enhanced field of view. On pathologic evaluation, there was no evidence of
perforation of either the right or left atrium outside of the fossa ovalis.
CONCLUSION: Both ICE catheters used in this trial allowed for excellent
visualization of the fossa ovalis and safe transseptal puncture. Intracardiac
echocardiography may be a better imaging modality than fluoroscopy for guiding
transseptal catheterization, especially in less experienced hands.
PMID- 9654230
TI - Origin of heat-induced accelerated junctional rhythm.
AB - INTRODUCTION: The application of high-frequency current to the AV junctional area
results in a temperature rise in the myocardium and may cause accelerated
junctional rhythm (AJR). The aim of the study was to characterize heat-induced
AJR in an in vitro animal model. METHODS AND RESULTS: Studies were performed in
isolated perfused pig and rabbit hearts. Using a small heating probe, we could
induce AJR from a discrete area located in the middle of the triangle of Koch,
which was smaller than the area from which RF energy application could elicit
AJR. Histology showed that the heat-sensitive area was located over, or close to,
the compact AV node. It did not correspond with the areas where double potentials
were found or with the site(s) of earliest atrial activation during VA
conduction. Microelectrode recordings revealed that AJR arose in nodal-type
cells. Heat increased the slope of the phase 4 depolarization and shortened the
action potential duration. Two types of AJR were observed: the first one was
regular and the second one showed irregularity in the intervals. Interaction of
multiple foci and the presence of conduction block between the foci and the His
bundle caused the irregularity of the His-His intervals during the second type of
AJR. CONCLUSION: AJR observed during heat and RF application in the AV nodal area
results from the effect of heat on AV nodal cells with underlying pacemaker
activity. The heat-sensitive area is located over, or very close to, the compact
AV node.
PMID- 9654231
TI - Familial sudden cardiac death associated with a terminal QRS abnormality on
surface 12-lead electrocardiogram in the index case.
AB - A case is presented of an 18-year-old male who had been resuscitated following an
episode of sudden death due to ventricular fibrillation. The patient was noted to
have an abnormal deflection in the terminal QRS on surface ECG and an abnormal
signal-averaged ECG demonstrating a late potential coincident with the terminal
QRS abnormality on the ECG. The patient had easily inducible polymorphic
ventricular tachycardia during electrophysiologic study, which was suppressed by
quinidine but not by procainamide or beta blockers. The surface ECG and signal
averaged ECG also were normalized by quinidine but not by procainamide or beta
blockers. The patient had no further arrhythmias on quinidine for 6 years until
he inexplicably discontinued his medication and died suddenly shortly thereafter.
The present case may represent a unique familial sudden death syndrome or
possibly a variant of the sudden death syndrome associated with right bundle
branch block and ST elevation in V1 through V3. Currently available data suggest
that, in such patients, an implantable cardioverter defibrillator may provide
better protection from sudden death than does antiarrhythmic drug therapy.
PMID- 9654232
TI - Emergence of bidirectional accessory pathway conduction in adulthood.
AB - A 30-year-old woman presented with tachycardiomyopathy due to atrial flutter
fibrillation and underwent radiofrequency ablation of the AV node and VVIR
pacemaker implantation. There was no evidence of any accessory pathway (AP)
conduction during the AV nodal ablation or during chronic ventricular pacing. One
year later, she had a transient preexcited tachycardia. A year after this, her
ECG showed 1:1 AV conduction with preexcitation. Electrophysiologic study
revealed a left lateral AP with anterograde and retrograde refractory periods of
280 and 240 msec, respectively. Successful radiofrequency ablation of the AP was
performed. This case highlights a unique emergence of an AP in adult life.
PMID- 9654233
TI - Becker muscular dystrophy with bundle branch reentry ventricular tachycardia.
AB - This report describes a case of Becker muscular dystrophy presenting with
recurrent symptomatic wide complex tachycardia. Electrophysiologic testing
demonstrated the mechanism to be bundle branch reentry ventricular tachycardia.
It is important to consider this potential mechanism in patients with ventricular
arrhythmias who have this particular clinical entity, since radiofrequency
catheter ablation can represent a curative treatment.
PMID- 9654234
TI - Effects of gender on cardiac arrhythmias.
AB - The purpose of this study is to review published data regarding gender
differences in cardiac electrophysiology and in the occurrence of clinical
arrhythmias. ECG differences between men and women include a faster resting heart
rate in women, a longer corrected QT interval, and a lower QT dispersion than in
men. The faster resting heart rate in women appears to be primarily related to
differences in physical conditioning. The mechanism for the longer corrected QT
interval in women is not completely known, but does not appear to be related to
acute effects of estrogen or progesterone or differences in autonomic
innervation. Women also appear to have a lower incidence of atrial fibrillation,
a difference in the age distribution of supraventricular tachycardia, and a lower
incidence of sudden death than men. Much of the lower incidence of sudden death
in women may relate to a difference in the prevalence of coronary artery disease,
but other factors such as inherent differences in repolarization, which may be
reflected by a gender difference in the corrected QT interval, also may be
operative. The paradox of a longer corrected QT interval and higher incidence of
torsades de pointes, but lower population-based incidence of sudden death in
women, has not been completely resolved. Further studies will be required to help
better understand the basic mechanisms involved in gender differences in
electrophysiology and arrhythmias and determine the extent to which these
differences have implications for clinical management of cardiac arrhythmias.
PMID- 9654235
TI - Sex steroids and cardiac arrhythmia: more questions than answers.
PMID- 9654236
TI - Management of patients with the hereditary long QT syndrome.
AB - The hereditary long QT syndrome is an inherited ion channel disorder with QT
prolongation, morphologic changes in the T waves, and a relatively high frequency
of syncope, T wave alternans, torsades de pointes-type ventricular tachycardia,
and sudden death. Monotherapy with beta blockers is the treatment of first
choice. In patients with recurrent syncope despite therapy with beta blockers,
pacemakers and/or ganglionectomy may be useful in selected cases, with an
implantable cardioverter defibrillator used as a fail-safe approach in high-risk
patients.
PMID- 9654237
TI - Narrow QRS complex tachycardia with apparent 2:1 QRS to P wave ratio.
PMID- 9654238
TI - Follow-up biological and genotoxicological monitoring of acrylonitrile- and
dimethylformamide-exposed viscose rayon plant workers.
AB - In order to investigate the genotoxic effects of occupational acrylonitrile (ACN)
and dimethylformamide (DMF) exposures, clinical serum and urine parameters and
genotoxicological endpoints such as chromosome aberration (CA), sister chromatid
exchange (SCE), high frequency SCE (HFC), cell cycle kinetics, and UV-induced
unscheduled DNA synthesis (UDS) were followed up three times during a 20-month
period in peripheral blood lymphocytes (PBL) of 26 workers (13 maintainers and 13
fiber producers) occupationally exposed to ANC and/or DMF in a viscose rayon
plant, 26 matched control subjects, and six industrial controls (all males). Six
of the 26 exposed subjects were hospitalized because of liver dysfunction that
had developed due to inhalative DMF exposure. The rate of smoking was estimated
on the basis of serum thiocyanate (SCN) levels. Average peak air ACN and DMF
concentrations were over the maximum concentration limits at the time of both
investigations. Urine ACN and monomethyl-formamide (MMF) excretions of the
exposed subjects were almost doubled after work shifts. An increase in lymphocyte
count (in months 0 and 7), and severe alterations in the liver function were
observed in the exposed subjects. In PBLs the proliferative rate index (PRI) was
already increased in month 0 compared with the controls. In each study,
significant increases in CA and SCE frequencies, as well as increases in UDS were
found in PBLs of the exposed subjects. The frequencies of chromatid breaks and
acentric fragments further increased in month 7 and remained constantly elevated
in month 20. Increased yields of both chromatid and chromosome-type exchange
aberrations first appeared in month 20, when HFCs were 2.72 times more frequent
in fiber producers than in maintainers. The role of some important biological
confounding factors (age, white blood cell count, and hematocrit) and lifestyle
confounding factors (smoking and drinking habits) were subjected to an analysis
of variance during the second study. Increased CA, SCE, and UDS were found both
in control and exposed smokers when current smoking was established on the basis
of the serum SCN levels. The cytogenetic data suggest that occupational exposures
to ACN and DMF induce considerable genotoxic consequences and may increase the
cancer risk in the exposed human populations.
PMID- 9654239
TI - Influence of GSTT1 genotype on sister chromatid exchange induction by styrene-7,8
oxide in cultured human lymphocytes.
AB - The genetic polymorphisms of glutathione S-transferases (GSTs), which are
involved in the metabolic inactivation of various toxicants, have been suggested
to be an important source of variation in individual response to genotoxic
carcinogens. We have previously shown that donor GSTM1 genotype does not
influence the induction of sister chromatid exchanges (SCEs) in cultured human
lymphocytes by styrene-7,8-oxide (SO), a metabolite of styrene. Here, we expanded
the study to GSTT1 polymorphism. SCEs were analyzed from 72-hr whole-blood
lymphocyte cultures of five GSTT1 positive (at least one undeleted allele) and
five GSTT1 null (gene homozygously deleted) donors, all GSTM1 positive, after a
48-hr treatment with 50 microM and 150 microM SO. SO clearly increased SCEs in
cultures of all donors. The mean number of SCEs/cell induced by SO (individual
mean SCEs from acetone-treated control cultures subtracted) was 1.7 (50 microM)
and 1.4 (150 microM) times greater among the GSTT1 null individuals (4.83 at 50
microM, 18.98 at 150 microM) compared with the GSTT1 positive individuals (2.78
at 50 microM, 13.74 at 150 microM), the differences being statistically
significant (P=0.006 and P=0.022, respectively). These findings show that the
lack of the GSTT1 gene increases the genotoxic effects of SO in human whole-blood
lymphocyte cultures, suggesting that GSTT1 is involved in the detoxification of
SO in humans. Although glutathione conjugation is considered a minor metabolic
pathway for SO in vivo, the high GSTT1 activity in erythrocytes may be important
locally and might affect the level of genotoxic damage observed in peripheral
lymphocytes of styrene-exposed reinforced plastics workers. The GSTT1
polymorphism could also influence the urinary excretion of SO-specific
mercapturic acids.
PMID- 9654240
TI - Chromosome aberrations in vitro related to cytotoxicity of nonmutagenic chemicals
and metabolic poisons.
AB - Chromosome aberrations can occur by secondary mechanism(s) associated with
cytotoxicity, induced by chemicals that do not attack DNA. Aberrations are formed
from DNA double-strand breaks, and DSBs are known to be induced by nonmutagenic
(Ames test negative) noncarcinogens at toxic levels [Storer et al. (1996): Mutat
Res 368:59-101]. Here, 8 of 12 of these chemicals caused aberrations in CHO cells
at cytotoxic doses, and often only when cell counts (survival) at 20 hr
approached < or =50% of controls. Five of eight noncarcinogens (2,4,
dichlorophenol, dithiocarb, menthol, phthalic anhydride, and ethionamide) and one
of two equivocal carcinogens (bisphenol A) caused aberrations, usually over a
narrow dose range with steeply increasing cytotoxicity. Phthalic anhydride and
ethionamide were positive only at doses with precipitate. Phenformin was negative
even at toxic doses and ephedrine and phenylephrine were negative and gave little
toxicity. Aberrations were also induced by metabolic poisons, 2,4-dinitrophenol,
(uncouples oxidative phosphorylation), and sodium iodoacetate, (Nal; blocks ATP
production). Five of the chemicals that induced aberrations in CHO cells were
tested in human TK6 cells and four were positive, the fifth being equivocal.
Stable aberrations (translocations) were induced in human cells by Nal. Clearly,
chemicals can give "false-positive" results in the chromosome aberration assay at
cytotoxic levels, though cytotoxicity does not always produce aberrations, so
that further information (e.g., DNA reactivity) is needed to determine whether a
result is a "false-positive." Primary DNA-damaging chemicals such as alkylators
are also cytotoxic, but give strong increases in aberrations without marked
initial toxicity by the measures used here, although the aberrations they induce
do reduce long-term survival in colony-forming assays.
PMID- 9654241
TI - Specificity of base substitution mutations induced by the dietary carcinogens 2
amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) and 2-amino-3
methylimidazo[4,5-f]quinoline (IQ) in Salmonella.
AB - The base pair substitution mutational profiles induced by the heterocyclic amine
cooked food mutagens PhlP and IQ in Salmonella typhimurium strains TA100 and
TA1535 were determined by colony hybridization analysis. Both PhlP and IQ induced
predominantly GC-->TA transversions in strain TA100 (rfa,delta uvrB/pKM101) with
a pronounced preference for the second codon position (CCC--> CAC; 72% of total).
PhlP also reverted strain TA1535 (rfa, delta uvrB) efficiently at concentrations
similar to those required for strain TA100. In contrast to the PhlP-induced
mutational profile observed in strain TA100, in strain TA1535 PhlP induced
exclusively GC-->AT transitions at the second codon position (CCC-->CTC; 96-99%
of total). Base substitution mutagenesis induced by heterocyclic amines related
to PhlP is generally SOS-dependent, requiring the presence of plasmid pKM101 in
Salmonella hisG46 strains. Thus, the SOS dependent reversion of S. typhimurium
strain TA100 probably reflects error-prone lesion bypass at the major PhlP-
guanosine adduct at the C-8 position. The GC-->AT transition mutations induced by
PhlP in strain TA1535 appear to be SOS-independent, however, suggesting that
these mutations may arise from the formation of PhlP-DNA adducts other than the
replication-blocking C8-dG lesion.
PMID- 9654242
TI - Monofunctional adenine N-3 adducts of melphalan: occurrence at a mutational
hotspot sequence and resistance to removal by AlkA protein.
AB - Previous work showed that a CTAAA sequence in the supF gene of the shuttle
plasmid pZ189 was a hotspot for mutagenesis by the aromatic nitrogen mustards
melphalan and chlorambucil, and indirect evidence suggested adenine N-3 adducts
as premutagenic lesions. In order to characterize the adducts formed at this
sequence more directly, a substrate was prepared in which the three adjacent
adenines in the CTAAA sequence were 3H-labeled. Following treatment of this
substrate with [14C]melphalan, thermolabile adducts were depurinated and analyzed
by HPLC. Only a single peak bearing both 3H and 14C label was detected and it
coeluted with the single major adduct formed by the reaction of melphalan with
free adenine base. Various spectrometric analyses of this species were all
consistent with its identification as a monofunctional adenine N-3 adduct of
melphalan. There was no evidence for any bifunctional adducts involving the
labeled adenines. There was little if any release of the adenine N-3 adduct of
melphalan by Escherichia coli AlkA protein, under conditions where 3
methyladenine was quantitatively released. The results support the proposal that
monofunctional adenine N-3 adducts are intermediates in the generation of A.T-
>T.A and A.T-->C.G transversions by aromatic nitrogen mustards.
PMID- 9654243
TI - An automated method for discriminating aneugen- vs. clastogen-induced
micronuclei.
AB - A flow cytometric (FCM) procedure for quantitating micronucleated reticulocytes
in mouse peripheral blood samples was evaluated for its ability to discriminate
between aneugen- and clastogen-induced micronuclei (MN). In this experiment,
BALB/c mice were injected with 0.9% saline, the model clastogen methyl
methanesulfonate (100 mg/kg bw) or the aneugen vincristine (0.2 mg/kg bw).
Peripheral blood samples were collected 48 hr after injection and were
subsequently fixed and stained for flow cytometric analysis. The staining method
utilized FITC-conjugated anti-CD71 to differentially label reticulocytes, and the
nucleic acid dye propidium iodide to resolve erythrocyte populations with and
without micronuclei. The frequency of micronucleated reticulocytes was determined
by analyzing 10,000 total reticulocytes per blood sample. A second analysis was
performed on each sample whereby the propidium iodide associated fluorescent
signals of 250 MN were collected and graphed as a single-parameter histogram. The
histogram statistic "median channel" was recorded for each sample and provided a
quantitative description of MN distribution according to DNA content.
Cumulatively, the results of this study suggest that 1) flow cytometry can be
employed to measure the incidence of MN resulting from clastogenic or aneugenic
activity, and 2) MN resulting from aneugens can be discriminated from those
arising spontaneously or from clastogen treatment based on flow cytometric
analysis of DNA content.
PMID- 9654244
TI - Comparative genotoxicity of quinolone and quinolonyl-lactam antibacterials in the
in vitro micronucleus assay in Chinese hamster ovary cells.
AB - The in vitro micronucleus assay is gaining increased attention as a potential
alternative to the standard in vitro metaphase analysis assay. In particular, the
in vitro micronucleus assay has been proposed as a useful method for chemicals
that induce both structural and numerical chromosome alterations, such as DNA
gyrase/topoisomerase inhibitors. In this study, we compared the micronucleus
inducing activity of quinolonyl-lactam antibacterials that inhibit DNA-gyrase and
bind to penicillin-binding proteins relative to the activity of structurally
related quinolone antibacterials that also inhibit DNA-gyrase. All of the
quinolones that were structurally related to the quinolonyl-lactams were
cytotoxic and induced large increases in the frequency of micronucleated
binucleated cells (MNBC) at concentrations between 0.02 and 0.16 mM. These
changes were larger than those seen with the commercial quinolones, ciprofloxacin
(cytotoxic at > or = 0.57 mM and MNBC at > or = 0.3 mM) and nalidixic acid
(cytotoxic at 1.8 mM and no MNBC up to this dose). In contrast, the quinolonyl
lactams were not cytotoxic up to 1.0 mM concentrations and induced either no MNBC
or a low frequency of MNBC at higher concentrations compared to the quinolones.
Quinolonyl-lactams appear to be less cytotoxic and genotoxic than structurally
related quinolones. These results add to the growing database on the in vitro
micronucleus assay in general, and more specifically to the relatively small
database for the in vitro micronucleus assay in Chinese hamster ovary cells.
PMID- 9654245
TI - Lead and mercury mutagenesis: role of H2O2, superoxide dismutase, and xanthine
oxidase.
AB - It has been suggested that reactive oxygen intermediates (ROIs) may have a role
in the genotoxic effects of lead (Pb2+) and mercury (Hg2+), but there have not
been any definitive studies demonstrating a causal relationship between the
induction of ROIs by these metals and mutagenesis. We previously demonstrated,
using the transgenic Chinese hamster ovary cell line AS52, that low
concentrations (0.1-1 microM) of Pb2+ and Hg2+ are mutagenic. In the present
study, using a novel histochemical computer-enhanced image analysis technique, we
demonstrate that Pb2+ and Hg2+ induce the formation of H2O2 in AS52 cells by at
least two distinct mechanisms. One is characterized by the rapid induction of
H2O2 following treatment of cells with concentrations of Pb2+ or Hg2+ below 0.8
and 1 microM, respectively, while the second occurs in AS52 cells treated with
concentrations of Pb2+ or Hg2+ greater than 0.8 and 1 microM, respectively. Pb2+
and Hg2+ (0.1-1 microM) had no effect on the activities of partially purified
catalase, glutathione peroxidase, or glutathione reductase, important enzymes
involved with antioxidant defense, but these metals stimulated the activities of
copper-zinc superoxide dismutase (CuZn-SOD) and xanthine oxidase (XO).
Allopurinol (50 microM), a specific inhibitor of xanthine oxidase, inhibited the
induction of H2O2 by Pb2+ (0.8-1 microM) and Hg2+ (1 microM) and also inhibited
Pb2+- and Hg2+-induced mutagenesis. These results demonstrate that Pb2+ and Hg2+
disrupt the redox status of AS52 cells by enhancing the activities of CuZn-SOD
and XO. Furthermore, the results of these studies also demonstrate that there is
a causal relationship between the induction of H2O2 by these metals and
mutagenesis.
PMID- 9654246
TI - S-oxygenation of thiourea results in the formation of genotoxic products.
AB - Thiourea (TU) is a thyroid carcinogen which has previously been shown to cause
genotoxicity in various test systems in vitro and in vivo. The mechanism
underlying these effects has not yet been elucidated. The present study addressed
the question of whether the formation of oxidized products of TU might be
involved in genotoxicity. Chemical oxidation of [14C]TU with hydrogen peroxide in
the presence of calf thymus DNA resulted in the formation of [14C]formamidine
sulfinate ([14C]FASA), [14C]cyanomide, and [14C]urea and in covalent binding of
radioactivity to the DNA. Incubation of V79 Chinese hamster cells with 10-20 mM
TU for 18 hr but not for 3 hr, increased the frequency of micronuclei to a slight
extent. In cells depleted of glutathione, which can prevent the oxidation of TU,
micronucleus induction by TU was more pronounced and detectable both after 3 and
18 hr of incubation. Exposure of the cells to 1.25 to 10 mM FASA for 3-5 hr
induced micronuclei, DNA repair synthesis, and gene mutations in the cells.
Flavin-containing monooxygenase (FMO], an enzyme known to catalyze the S
oxygenation of TU in liver, could not be detected in the postmitochondrial
supernatant (S-9) of the V79 cells. There is evidence, however, that TU can
easily autoxidize to S-oxygenated products. Both FASA and TU caused a slight
induction of DNA repair synthesis in cultured rat hepatocytes, but FASA was
active at lower concentrations than TU. Cyanamide did not elicit repair. The
finding that FASA, a product of both the nonenzymatic and the enzymatic S
oxygenation of TU, is genotoxic in cultured mammalian cells provides for the
first time a hypothesis to explain the genotoxicity of TU.
PMID- 9654247
TI - Comparison of sensitivity to methyl methanesulphonate among tadpole developmental
stages using the alkaline single-cell gel electrophoresis (comet) assay.
AB - In a previous study, we demonstrated that tadpoles are suitable organisms for
monitoring small bodies of water (e.g., creeks, ponds, and drainage ditches) for
genotoxicity using the alkaline single-cell gel DNA electrophoresis (SCG) or
"comet" assay [Ralph and Petras, 1997]. This approach involves detection, under
alkaline conditions, of cell DNA fragments which on electrophoresis migrate from
the nuclear core, resulting in a "comet with tail" formation. In this initial
study, most of the tadpoles collected were in the early stages of larval
development, but this is not always possible. The present study evaluated the
sensitivity of tadpoles, at different stages of larval development, to a range of
concentrations of the genotoxicant methyl methane-sulphonate (MMS). Four specific
phases of Rana clamitans (green frog) larval development were examined: first
year limbless tadpoles (Stage I as defined by Taylor and Kollros [1946]), second
year limbless tadpoles (Stages II-III), second-year tadpoles with only hindlimbs
(Stages X-XVIII), and second-year tadpoles with all four limbs evident and a tail
undergoing resorption (Stages XXII-XXIII). Twenty-four hour exposures to MMS of
tadpoles in the three earliest phases produced a significant (P < 0.01) added
variance component among tadpoles for DNA damage and there were significant
increases (P < 0.05) in the length:width ratios of the DNA patterns at
concentrations as low as 1.56 mg/I. However, tadpoles in the last phase studied
(both pairs of limbs present) showed no significant (P > 0.05) added variance
component and no significant increases (P> 0.05) in DNA damage upon exposure to
any of the MMS doses tested. A nested ANOVA indicated that, for each of the
tested concentrations of MMS, but not the dechlorinated water control, there was
significant heterogeneity (P < 0.05) in DNA damage when tadpoles of all four
phases studied were compared. However, when tadpoles of the lost phase of
development were removed from the comparison, there was no significant
heterogeneity (P > 0.05) among tadpoles of the remaining three phases. Possible
reasons for this insensitivity to MMS as animals enter the metamorphic climax
were considered. The results indicate that pooling of the early tadpole phases of
R. clamitans for SCG environmental genotoxicity biomonitoring is acceptable.
PMID- 9654248
TI - Unicellular green alga Chlamydomonas reinhardtii as an activation system for 2
aminofluorene.
AB - Despite the promutagenic/procarcinogenic potential, polycyclic aromatic amines
are widely spread in the environment. Biotransformation of the polycyclic
aromatic amine 2-aminofluorene (2-AF) was proved in mammals and higher plants.
The algal cell/microbe coincubation assay is an additional system that
complemented those proved in mammals and higher plants, useful for detection and
conversion of environmental promutagens, mainly in aquatic environments. The
unicellular green algae may be a good activating system in coincubation assays in
that the algal cells exist as a natural system. To increase the effectiveness of
this metabolizing system, different modifications of the standard experimental
procedure were conducted. Algae can accumulate and metabolize promutagenic
pollutants, some of which may differ from those activated by the animal microsome
metabolizing system (S9 mix) and by the plant cell/microbe coincubation assay. 2
AF was activated in the algal cell/ microbe coincubation assay in which wild-type
Chlamydomonas reinhardtii cells were used as an activating system and the
bacteria Salmonella typhimurium TA98, YG1024, and yeast Saccharomyces cerevisiae
D7 as the genetic indicator organisms. It was converted to the mutagenic
product(s) for the strain YG1024, but the strain TA98 did not exhibit any
increase in the mutant yield of His+ revertants. Consequently, metabolites from 2
AF are substrates for O-acetyltransferase. A direct comparison of algal 2-AF
activation with mammalian activation system (S9 mix) proved the higher activity
of mammalian microsome system (S9 mix). After the combination of both activation
systems, a slight synergetic effect was found. Although the genetic endpoints
induced by 2-AF using both modifications of the algal cell/S. cerevisiae
coincubation assay and those obtained in intact yeast cells were similar at the
equitoxic concentrations, 2-AF activation by the algal supernatant slightly
increased the genetic endpoints studied.
PMID- 9654249
TI - Biotransformation of several structurally related 2B compounds to reactive
metabolites in the somatic w/w+ assay of Drosophila melanogaster.
AB - Biotransformation of several structurally related 2B compounds to reactive
metabolites was evaluated in the somatic w/w+ assay of Drosophila melanogaster.
Chemicals tested were the dichlorinated alkanes dichloromethane (DCM), 1,2
dichloroethane (DCE), and 1,3-dichloropropane (DCP); the thiouracil derivatives 5
methyl, 2-thiouracil (5M2TU), 6-methyl, 2-thiouracil (6M2TU), and 5-propyl, 2
thiouracil (5P2TU); and the plastic monomer styrene (STY) and its metabolite
styrene 7,8-oxide (SO). The tester strains used consisted of one wild-type
insecticide-susceptible (IS) laboratory strain (Leiden-S, ST), and two
insecticide-resistant (IR) strains (Hikone-R, HK, and Haag-R, HG). The latter
have high cytochrome P450-dependent bioactivation capacities. Drosophila larvae
heterozygous for the wild-type report gene w+ were exposed chronically to at
least three different exposure doses of each compound. A total of 53,694 eyes
were analyzed. A positive genotoxic activity was obtained for DCM and for 6M2TU
at all exposure doses and genotypes analyzed, and for SO in the IR strains HK-R
and HG-R. An overall weakly recombinagenic response was shown by DCE and 5M2TU.
The chemicals DCP, 5P2TU, and STY proved to be overall negative in IR as well as
in IS strains, and SO was negative in the standard stock. Biotransformation
mediated by cytochrome P450 monoxigenases to reactive metabolites is discussed.
PMID- 9654250
TI - Mutagenicity and clastogenicity of gas stove emissions in bacterial and plant
tests.
AB - The aim of this research was to study the gaseous and particulate emissions of
genotoxic substances during cooking with two types of methane stoves (a new one
and an old one). The particulates were sampled both with a cascade impactor air
sampler and an impinger with ice trap and analyzed by two bacterial mutagenicity
tests (Ames and Kado tests) and by HPLC for polycyclic aromatic hydrocarbons
(PAH). Gaseous emissions were studied in situ using the Ames test, a
clastogenicity plant test (Tradescantia-micronucleus test), and in an automated
system for chemical analyses. Clear indirect mutagenicity was found only with the
Kado test (TA98-S9) in extracts of particulates emitted from the old methane
stove and collected with the impinger. Similar mutagenicity (TA98+S9) was also
found for the finest fraction of particulates (<0.5 um) collected from both
stoves. Gaseous emissions of both stoves caused clastogenicity in the in situ
experiments with the Tradescantia-micronucleus test. The physico-chemical
analyses of the emissions showed also the presence of very fine particulates and
trace amounts of PAH. The exposure of these genotoxins could be particularly
important for occupationally exposed individuals in homes and businesses and for
susceptible subjects living indoors for long periods (infants, children, the
sick, and the elderly).
PMID- 9654251
TI - Facing up to the acute coronary syndromes.
PMID- 9654252
TI - How should doctors respond to the GMC's judgments on Bristol?
PMID- 9654253
TI - Adjuvant IFN alpha2 therapy of melanoma.
PMID- 9654254
TI - Genetic influence on HDL cholesterol.
PMID- 9654255
TI - Antithrombotics for left-ventricular impairment?
PMID- 9654256
TI - Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary
melanoma thicker than 1.5 mm without clinically detectable node metastases.
French Cooperative Group on Melanoma.
AB - BACKGROUND: Owing to the limited efficacy of therapy on melanoma at the stage of
distant metastases, a well-tolerated adjuvant therapy is needed for patients with
high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with
low doses of interferon alpha could be effective in patients with localised
melanoma. METHODS: After resection of a primary cutaneous melanoma thicker than
1.5 mm, patients without clinically detectable node metastases were randomly
assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for
18 months, or no treatment. The primary endpoint was the relapse-free interval.
FINDINGS: 499 patients were enrolled, of whom 489 were eligible. When used as
part of a sequential procedure, interferon alpha-2a was of significant benefit
for relapse-free interval (p=0.038). A long-term analysis, after a median follow
up of 5 years, showed a significant extension of relapse-free interval (p=0.035)
and a clear trend towards an increase in overall survival (p=0.059) in interferon
alpha-2a-treated patients compared with controls. There were 100 relapses and 59
deaths among the 244 interferon alpha-2a-treated patients compared with 119
relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates
were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death
rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade
3 or 4 adverse events. Treatment was compatible with normal daily life.
INTERPRETATION: Adjuvant therapy of high-risk melanoma with low doses of
interferon alpha-2a for 18 months is safe and is beneficial when started before
clinically detectable node metastases develop.
PMID- 9654257
TI - DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma.
AB - BACKGROUND: Cystic fibrosis is a recessive disorder mainly characterised by lung
disease. We tested the hypothesis that individuals heterozygous for the common
cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease.
METHODS: We studied a cross-sectional sample from the general population of
Copenhagen, Denmark, aged 20 years and older. We did spirometry to measure forced
expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), and did
genotyping on blood samples of 9141 individuals. We asked all participants
whether they had asthma, and asked for information on smoking and other factors
that could have contributed to obstructive pulmonary disease. FINDINGS: We
identified 250 carriers of the deltaF508 mutation (2.7% [95% CI 2.5-3.1]). 9% of
carriers reported having asthma compared with 6% of non-carriers (p=0.04). The
odds ratio for asthma in participants heterozygous for deltaF508 mutation was 2.0
(1.2-3.5, p=0.02). Furthermore, among individuals with airway obstruction, the
percentage predicted FEV1 and FVC were significantly lower in participants
heterozygous for deltaF508 than in non-carriers (49 vs 58%, p=0.004; and 70 vs
82%, p<0.001, respectively), mainly due to an effect in those with self-reported
asthma. INTERPRETATION: Cystic fibrosis deltaF508 heterozygosity may be over
represented among people with asthma and seems to be associated with decreased
pulmonary function in people with airway obstruction who also have asthma.
PMID- 9654258
TI - Relation between laboratory test results and histological hepatitis activity in
individuals positive for hepatitis B surface antigen and antibodies to hepatitis
B e antigen.
AB - BACKGROUND: Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e
antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to
assess histological hepatitis activity. An optimum panel of tests has not been
found and the usefulness of hepatitis B virus (HBV) DNA assays in this context
has not been established. We assessed various blood tests to find which best
predicted hepatitis activity. METHODS: Routine plasma biochemical liver tests and
serum HBV DNA (hybridisation and PCR assays) were assessed prospectively in 123
patients positive for HBsAg and anti-HBe. We scored histological hepatitis
activity (hepatitis activity index) and determined whether chronic active
hepatitis (chronic hepatitis with portal and periportal lesions) was present. We
analysed the relation between laboratory data and the hepatitis activity index or
risk of chronic active hepatitis by multiple regression and multiple logistic
regression, respectively. FINDINGS: The analyses provided models for predicting
either the hepatitis activity index or the risk of chronic active hepatitis.
Aspartate aminotransferase was the most important test in the two models. The
contribution of HBV DNA and other assays, especially alanine-aminotransferase
activity, were of no practical importance. INTERPRETATION: Because screening by
aspartate-aminotransferase activity could not be improved by the addition of
other assays or HBV DNA, patients positive for HBsAg and anti-HBe could be
screened for chronic active hepatitis with a single assay and counselling of
patients can be improved if proper reference values are used.
PMID- 9654259
TI - Beta-glucocerebrosidase gene locus as a link for Gaucher's disease and familial
hypo-alpha-lipoproteinaemia.
AB - BACKGROUND: Gaucher's disease is the most common lysosomal storage disorder,
caused by deficiency of glucocerebrosidase resulting from homozygosity for any of
several mutations of the glucocerebrosidase gene locus. Affected people have
decreased concentrations of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C).
We assessed the association between mutations in the glucocerebrosidase locus and
hypo-alpha-lipoproteinaemia. METHODS: We studied 258 people from 43 unrelated
Spanish families. 57 participants were affected, 137 were non-affected carriers,
and 64 were non-carriers. We determined glucocerebrosidase genotypes and measured
plasmid lipids, apolipoproteins A-I, B, and E, and leucocyte glucocerebrosidase
activity. FINDINGS: The most common glucocerebrosidase mutations were N370S
(45%), L444P (23%), and G377S (5%). Deletions and recombinants accounted for
another 5%, and point mutations in exons 5, 6, 9, and 10 were present in 12%.
Affected participants had lower LDL-C and HDL-C concentrations than non-affected
carriers (p<0.001) and non-carriers (p<0.001). HDL-C values were also
significantly different between the non-affected carriers and non-carriers.
Mutations at this locus may account for as much as 19.5% of the genetic
variability in HDL-C in the population studied. INTERPRETATION: Heterozygosity
for these mutations at the glucocerebrosidase locus does not result in clinical
expression of Gaucher's disease but can decrease HDL-C concentrations. Given the
high frequency of these mutations, the glucocerebrosidase locus might lead to
familial low alpha-lipoproteinaemia in up to 2% of the general population and be
one of the most common known genetic causes of HDL-C.
PMID- 9654260
TI - Death from heroin overdose: findings from hair analysis.
AB - BACKGROUND: Morphine analysis of hair is used in forensic toxicology to study the
addiction history of heroin addicts. To clarify the features underlying fatal
heroin intake, we measured hair morphine content in a group of deceased heroin
addicts, to verify a possible correlation between fatal heroin overdoses and the
addiction behaviour of these individuals before death. METHODS: 91 deaths were
attributed to heroin overdose in Verona, Italy, in 1993-96. We analysed the hair
of 37 of these individuals, and of 37 active heroin addicts, 37 former heroin
users abstinent from the drug for several months, and 20 individuals with no
evidence of exposure to opioids. From each individual, a hair sample of about 150
mg was analysed by RIA and high-performance liquid chromatography, to measure the
morphine content. FINDINGS: The mean morphine content in the hair of the addicts
who had died was 1.15 ng/mg (SD 2.35 ng/mg; range 0-12.25 ng/mg) compared with
6.07 ng/mg (4.29; 1.15-17.0) in the active heroin addicts, 0.74 ng/mg (0.93; 0.10
3.32) in the abstinent former addicts, and values below the detection limit in
the non-exposed group. Hair morphine content among those who had died was
significantly lower than that in active heroin consumers (p<.00001), but not
significantly different from that in the former addicts (p=0.978).
INTERPRETATION: Although our findings may be subject to selection bias, since
suitable hair samples were available for only 37 of the 91 addicts who had died,
these findings support the theory of high susceptibility to opioid overdose after
periods of intentional or unintentional abstinence, due to loss of tolerance.
Medical staff running detoxification programmes should be aware of the risk
inherent in relapse to heroin after a period of abstinence. Moreover, occasional
heroin use without a build-up of tolerance could also give a high risk of
overdose.
PMID- 9654261
TI - A 35-year-old bricklayer with hemimyoclonic jerks.
PMID- 9654262
TI - Rates of first measles-mumps-rubella immunisation in Wales (UK)
PMID- 9654263
TI - Clinically occult pelvic-vein thrombosis in cryptogenic stroke.
PMID- 9654264
TI - Sodium antimony gluconate, amphotericin, and myocardial damage.
PMID- 9654265
TI - Rhabdomyolysis due to interaction of simvastatin with mibefradil.
PMID- 9654266
TI - Raised plasma soluble Fas and Fas-ligand in alcoholic liver disease.
PMID- 9654267
TI - Prognostic value of Th1/Th2 ratio in rheumatoid arthritis.
PMID- 9654268
TI - Salivary urate in gout, exercise, and diurnal variation.
PMID- 9654269
TI - Uncoupling protein-3 expression in skeletal muscle and free fatty acids in
obesity.
PMID- 9654270
TI - C282Y mutation in HFE (haemochromatosis) gene and type 2 diabetes.
PMID- 9654272
TI - UK "Bristol case" doctors found guilty of misconduct.
PMID- 9654271
TI - Somesthetic aura: the experience of "Alice in Wonderland".
PMID- 9654273
TI - "Personalised" drug therapy could be near.
PMID- 9654274
TI - Mike Dexter: a forthright view of biomedical science.
PMID- 9654275
TI - Bad blood in US genome research.
PMID- 9654276
TI - Hollow celebration of 50 years of human-rights campaigning.
PMID- 9654277
TI - Kindling a conscience for the biotech industry.
PMID- 9654278
TI - Intracoronary stenting.
PMID- 9654279
TI - The case for allowing kidney sales. International Forum for Transplant Ethics.
PMID- 9654280
TI - Mission-oriented research: a case study.
PMID- 9654281
TI - If children's lives are precious, which children?
PMID- 9654282
TI - Locking the door: US imprisonment of asylum seekers.
PMID- 9654283
TI - Forensic medicine: international criminal tribunals and an international criminal
court.
PMID- 9654284
TI - Vascular complications associated with use of HIV protease inhibitors.
PMID- 9654285
TI - Vascular complications associated with use of HIV protease inhibitors.
PMID- 9654286
TI - Vascular complications associated with use of HIV protease inhibitors.
PMID- 9654287
TI - Vascular complications associated with use of HIV protease inhibitors.
PMID- 9654288
TI - Meta-analysis.
PMID- 9654289
TI - Effectiveness of pneumococcal vaccine.
PMID- 9654290
TI - Effectiveness of pneumococcal vaccine.
PMID- 9654291
TI - Prophylactic antibiotics before insertion of intrauterine devices.
PMID- 9654292
TI - Intrauterine devices in HIV-1-infected women.
PMID- 9654293
TI - Oral melatonin in neurologically disabled children.
PMID- 9654294
TI - Oral melatonin in neurologically disabled children.
PMID- 9654295
TI - Japanese encephalitis virus and poliomyelitis-like illness.
PMID- 9654296
TI - Opiates for sickle-cell crisis?
PMID- 9654297
TI - Opiates for sickle-cell crisis?
PMID- 9654298
TI - Opiates for sickle-cell crisis?
PMID- 9654299
TI - Catechol-O-methyltransferase inhibitors in Parkinson's disease.
PMID- 9654300
TI - Catechol-O-methyltransferase inhibitors in Parkinson's disease.
PMID- 9654301
TI - MERLIN and malaria epidemic in north-east Kenya.
PMID- 9654302
TI - Antiepileptic drugs in developing countries.
PMID- 9654303
TI - The RAGE litigation. Radiation Action Group Exposure.
PMID- 9654304
TI - Scaling prison walls.
PMID- 9654306
TI - Surgical invasion and infection conference: introductory remarks.
PMID- 9654307
TI - A microbiologist's view of factors contributing to infection.
AB - Why some patients develop postoperative surgical wound infection and others do
not remains a mystery. There are many risk factors for infection, and
mathematical scoring systems are often good predictors of infection; yet, some
patients with a plethora of risk factors fail to develop surgical site
infections. Even patients with established abdominal infection do not
automatically develop wound infection. Early experimental work, now confirmed in
the clinical setting, dictates that bacteria must be in the wound to cause
infection; the minimal infecting dose will depend on the environmental conditions
in the wound. The presence of foreign bodies, trauma, hematoma, etc., will
enhance the effect of the inoculum; therefore, surgical debridement and careful
surgery are necessary to reinforce the host defenses. Some bacteria, e.g.,
Staphylococcus aureus and Streptococcus pyogenes, have a greater propensity to
cause infection, so extensive infection-control practices are necessary to
prevent or contain these pathogens. To minimize the risk of surgical site
infection, individual patient risk factors must be identified and modified
whenever possible. The patient should be prepared for the operation and
appropriate skin antiseptics should be used on the operative site. The patient
should be considered for perioperative antibiotic prophylaxis and, if
appropriate, bowel preparation should be carried out. Care and attention to the
theater operating environment is important, especially for cases in which
airborne transmission of bacteria should be controlled, e.g., ultraclean air
systems for implant surgery. In elective surgery, the source of bacteria that
cause infection is either the patient's normal flora (e.g., skin or bowel), i.e.,
endogenous, or the surgical staff or environment, i.e., exogenous. Surgical
expertise and theater discipline are essential components in the fight against
surgical sepsis.
PMID- 9654308
TI - Antibiotic prophylaxis.
AB - During the past 30 years, antibiotic prophylaxis has proved of enormous efficacy
in reducing the incidence of surgical wound infections, postoperative morbidity
and mortality, the duration of the postoperative period, and the overall cost of
surgical treatment. In this paper, the timing and route of administration of
antibiotic prophylaxis as well as the dosage and duration, the indications for
antibiotic prophylaxis, the importance of the alterations of the delayed
hypersensitivity response, and the value of antibiotic prophylaxis for prevention
of postoperative septic complications in anergic patients are analyzed. The
possibility of combining antibiotic prophylaxis with immunoprophylaxis for high
risk patients is also analyzed.
PMID- 9654309
TI - Contemporary wound infection surveillance issues.
AB - Contemporary wound infection surveillance is inexact. Tracking down suspicious
incisions with maximal accuracy to isolate the subset of healing failures
attributable to established tissue invasion by infecting pathogens has a solitary
purpose: to learn how to improve one aspect of surgical practice. Wound infection
is always the result of complex, probabilistic interplay of numerous concealed
variables. A wound infection rate, whether determined for a hospital, a
specialty, a risk class, an operation type, or a surgeon, only approximates a
degree of failure to achieve one kind of surgical perfection. Interpretation of
any rate will be flawed if issues of accuracy and meaning are suppressed.
Gathering and revealing circumstances of individual infections may heuristically
affect surgical teams. Interpretation of surveillance wound infection rates,
infection rate comparisons to standards as a means of performance measurement,
and particularly the meaning of rate changes over time in a hospital are matters
of more than academic importance. Given current health care reform and a
widespread fascination with industrial process-improvement philosophy, wound
infection surveillance programs may be natural test platforms for probing
surgical relevance of several quality-improvement methodologies. It is not a
trivial fact that wound infection shares important prototypical features with
most contemporary surgical care process flaws: rare, random, multifactorial in
cause, costly, and impossible to uniformly preclude or predict.
PMID- 9654310
TI - Ventilator-associated bacterial pneumonia: challenges in diagnosis, treatment,
and prevention.
AB - Ventilator-associated pneumonia (VAP) is a common infection in intensive care
unit patients that results in high mortality and morbidity and increased duration
of hospital stay. Clinical diagnostic methods are sensitive, but lack
specificity. Quantitative analysis of specimens from the lower respiratory tract
increases specificity. Bacteria causing VAP may originate from the patient's
endogenous flora, other patients or hospital personnel, or from environmental
sources. Aspiration or direct inoculation are the major routes of bacterial entry
into the lower respiratory tract. The bacterial inoculum and host response in the
lung are important factors for pathogenesis. Late-onset nosocomial pneumonia is
often caused by Pseudomonas aeruginosa, Acinetobacter species, and Staphylococcus
aureus. Streptococcus pneumoniae and Haemophilus influenzae, however, are the
more common pathogens in early-onset disease. Oropharyngeal and gastric
colonization with bacteria, cross-infection, as well as the indiscriminate use of
antibiotics or invasive devices substantially increase the risk of VAP. An
understanding of the epidemiology and pathogenesis of VAP, along with
implementation of appropriate preventive measures, are needed to decrease the
incidence, morbidity, and mortality associated with VAP.
PMID- 9654312
TI - Antibiotic prophylaxis in clean surgery: does it work? Should it be used if it
does?
AB - Perioperative antibiotic prophylaxis has been demonstrated to prevent
postoperative wound infection after clean surgery in a majority of clinical
trials with sufficient power to identify a 50% reduction in risk. The low risk of
infection after many clean procedures requires studies of more than 1,000
procedures (sometimes many more) to detect such reductions reliably. This is a
serious obstacle to performing conclusive tests of efficacy, and it all but
precludes use of conventional clinical trials to identify optimal regimens.
Regimens that have been shown to be effective have usually been those with
efficacy against Staphylococcus aureus and other pathogens that may be carried in
the nares or on the skin. In addition, relatively long half-life in the serum and
low cost are important considerations. Cefazolin is a good prophylaxis agent for
many clean surgical procedures, although special characteristics of the
procedure, increased likelihood of antimicrobial resistance, or antibiotic
utilization concerns may make other agents more suitable in specific situations
The decision to use perioperative antibiotic prophylaxis for clean surgical
procedures depends not only on its efficacy, but also on the cost of preventing
infection. Few cost-benefit analyses have been performed, especially for
procedures in which prophylaxis has been least used. To perform such analyses, it
will be necessary to acquire information that is currently lacking for many
procedures. This includes the risk and cost of postoperative infection, adverse
reactions to the prophylaxis agent, and increased antimicrobial resistance; in
addition, detailed information is needed on infection-associated costs of medical
care, lost productivity, and the value that the infected person places on
avoiding infection. For many procedures, timely use of an appropriate antibiotic
is the single most effective infection prevention method that can be implemented
and monitored on a broad scale. These features make it amenable to adoption as a
subject of continuous quality improvement activities. To accomplish this, it is
necessary to articulate standards of care clearly so that systems to support the
intended goal can be developed. Both the standards and the support systems can be
tailored to specific surgical situations and to the values of providers and
patients.
PMID- 9654311
TI - The role of oral antimicrobials for the management of intra-abdominal infections.
AB - BACKGROUND: Oral therapy for patients with complicated intra-abdominal infections
has been very limited because those patients are frequently ill and need surgery.
In addition, at the time of diagnosis and initial treatment, the infection is
often accompanied by ileus, gastrointestinal tract function is frequently
unknown, and many patients cannot tolerate oral intake. The use of oral
antimicrobials in this setting is a recent advance resulting from the
availability of agents with good tissue pharmacokinetics and potent aerobic gram
negative activity. This is the first prospective blinded study of oral therapy to
provide data on the characteristics of patients eligible for oral treatment and
the consequences of such treatment. STUDY DESIGN: In blinded fashion, patients
with complicated intra-abdominal infections were randomized to either i.v.
ciprofloxacin plus metronidazole or i.v. imipenem throughout their treatment
course, or i.v. ciprofloxacin plus metronidazole and treatment with oral
ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ
i.v./oral). Physicians could switch the patient to oral therapy between 3 and 8
days after the start of i.v. treatment. RESULTS: One hundred fifty-five of 330
(47%) patients were switched to active or placebo oral therapy. Patients who
received i.v./oral therapy were treated, overall, for an average of 8.6 +/- 3.6
days, with an average of 4.0 +/- 3.0 days of oral treatment. Of 46 CIP/MTZ
i.v./oral patients (active oral arm), treatment failure occurred in 2 patients
(4%) compared with 41 patients (23%) who were not switched to oral agents. No
patient or disease features, such as Acute Physiology and Chronic Health
Evaluation II score, severity of illness at study entry, organ source of
infection, or duration of treatment were identified as predictors of conversion
to oral treatment. CONCLUSIONS: In this first prospective examination of
sequential i.v./oral therapy for complicated intra-abdominal infections,
conversion to oral therapy with ciprofloxacin plus metronidazole appears as
effective as continued i.v. therapy for patients able to tolerate oral feedings.
Patients who can tolerate oral intake may be treated with appropriate oral
antimicrobials and are not at any significant increased risk for failure.
PMID- 9654313
TI - Bacterial colonization of prosthetic devices and measures to prevent infection.
AB - Prosthetic devices are used extensively in surgical practice. This includes
devices used on a temporary, intermittent, and long-term basis. In addition to
problems with biocompatibility, the main health care issue concerning prostheses
is the elevated risk of infection and the current inability to effectively
prevent and treat such infections. An appreciation of microbial biofilm
development has drawn attention to flaws in diagnosis and led to new methods to
attack the problem. Future remedies will likely involve utilization of new
biomaterial designs and application of either highly potent antimicrobials or
agents used in combination that penetrate biofilms and eradicate the organisms.
PMID- 9654314
TI - What is the value of preventing postoperative infections?
AB - The importance of postoperative infections depends on the frequency with which
infection occurs as well as on the additional cost per patient with infection.
For example, in our hospital the additional cost per patient with infection after
hernia repair was $600, compared with $2,106 per patient with infection after
colonic surgery. However, the total excess cost per year was similar for hernia
surgery ($44,800) and colon surgery ($48,440). The reason is that hernia surgery
is much more common than colon surgery. It is a general principle of clinical
audit that the importance of problems should be defined by their frequency as
well as their individual severity. A third important consideration is the
likelihood that the problem can be corrected. Undue attention has been given to
the health resource costs of postoperative infection at the expense of
information about the intangible costs to the patient (these are nonfinancial
costs such as pain and disability). Health resource costs are very dependent on
medical practice variation, and comparative studies between countries reveal
marked differences in the way that apparently similar infections are managed.
Moreover, comprehensive audit of infection-control management often reveals
wasteful practice, e.g, antibiotic treatment of patients who do not in fact have
infection. Audit of postoperative infection should focus on eliminating wasteful
practice (e.g., prophylactic antibiotics continuing > 24 hrs after surgery) as
well as on reducing postoperative infection rates.
PMID- 9654315
TI - Infections complicating pancreatitis: diagnosing, treating, preventing.
AB - The most important risk factor in patients suffering from acute necrotizing
pancreatitis is pancreatic infection, a factor that determines the course of the
disease, its therapeutic management, and its outcome. The bacterial infection
route is very likely via the colon. In patients with acute pancreatitis, the
infection rate is about 40 to 70% within the first 3 wks. Bacteria most
frequently found are those from the gastrointestinal tract: Escherichia coli,
Pseudomonas species, Streptococcus fecalis, Enterococcus, and Staphylococcus
aureus. Screening methods for infected necrotizing pancreatitis include fine
needle puncture by ultrasonography or computed tomographic guidance with Gram
staining and culture of the aspirate. We previously investigated different broad
spectrum antibiotics with regard to their efficacy at preventing infection. This
analysis indicated that antibiotics have different efficacy factors based on
pharmacodynamic properties. Imipenem and quinolones, in combination with
metronidazole, are the drugs of choice for treating or preventing pancreatic
infection, whereas aminoglycosides do not enter the pancreas and therefore are
not indicated. Based on increasing evidence that patients with acute necrotizing
pancreatitis will benefit by early and appropriate antibiotic therapy, we altered
the approach in such patients with an immediate start of antibiotic therapy
continued for at least 14 days. We have found a reduction of the infection rate
to 33% (11/32) in the third week after the onset of the disease. This treatment
of the infection and the possibility of delaying operative intervention resulted
in optimal surgical conditions. However, further prospective, controlled, and
randomized studies are necessary to determine which antibiotics and antimycotic
therapeutic regimens should be chosen.
PMID- 9654316
TI - Impact of laparoscopic surgery on stress responses, immunofunction, and risk of
infectious complications.
AB - Open laparotomy is followed by profound changes in endocrine metabolic function
and various host defense mechanisms, impaired pulmonary function, and hypoxemia,
all of which may be important for the development of postoperative infectious
complications. Laparoscopic surgery, however, leads to a reduced inflammatory
response (C-reactive protein and interleukin-6), a reduced immunomodulatory
response, improvement in pulmonary function, and less hypoxemia, whereas classic
endocrine metabolic responses are less influenced or not influenced compared with
similar open operation. The clinical implications of laparoscopic surgery on
postoperative infectious complications have not been assessed in large-scale
prospective, randomized studies, except in appendectomy, in which a reduced
incidence of wound infection has been demonstrated. Data from cholecystectomy and
colorectal surgery suggest a reduction in wound complications, whereas the sparse
data on intraperitoneal infections and sepsis are not conclusive. Thus,
laparoscopic surgery modifies the injury response and reduces the risk of
infectious complications. If integrated into an accelerated rehabilitation
program, further improvement may result. The impact of these findings on
prophylactic antibiotic regimens cannot be assessed from available data and
requires evaluation in prospective clinical studies.
PMID- 9654317
TI - Predicting the need for reoperation for abdominal infection.
AB - Abdominal infection complicating abdominal operation is a serious clinical
problem that is subject to diagnostic delay, which is a risk factor for adverse
outcomes. Clinical examination and laboratory and imaging modalities become more
accurate at achieving a diagnosis once the patient becomes sicker from infection
but cannot reliably predict the need for reoperation early in the postoperative
course. The Abdominal Reoperation Predictive Index scoring system synthesizes
common sense and objective measurements in an attempt to predict the need for
reintervention before it is too late. We encourage other centers to test this
predictor in their own patient populations.
PMID- 9654318
TI - Therapeutic immunomodulatory approaches for the control of systemic inflammatory
response syndrome and the prevention of sepsis.
AB - In the sequelae of massive traumatic stress, substantial impairment of
immunologic reactivity has been demonstrated to correlate clinically with
increased susceptibility to serious infection. Posttraumatic immune abnormalities
consist basically of two coexistent mechanisms: Hyperinflammation and depression
of cell-mediated immune responses. It is our understanding that the endogenous
ability of the organism to survive overwhelming trauma is insufficient and
requires exogenous support to prevent the conversion from systemic inflammatory
response syndrome to bacterial sepsis and septic shock. The objectives of
immunomodulatory interventions, which should be started as early as possible
after tissue destruction, include a) prevention of excessive macrophage
stimulation via neutralization of circulating endotoxins and exotoxins with high
doses of polyvalent immunoglobulin and soluble complement receptors, b) global
short-term (<72 hrs) down-regulation of inflammatory monocyte/macrophage and
polymorphonuclear neutrophil activity, and c) restoration of cell-mediated immune
performance to overcome posttraumatic functional paralysis. Among recent
promising strategies, the use of granulocyte-macrophage colony-stimulating
factor, pentoxifylline, and recombinant human interleukin-13 has been suggested,
all of them predominantly down-regulating the Mphi (monocyte/macrophage)
inflammatory potential. Cyclooxygenase inhibitors such as indomethacin and
thymomimetic peptides can help normalize the immunoreactivity by restoring the
forward-regulatory pathway of cell-mediated immunity responses. The efficacy of
interferon to reduce infection and deaths in severely injured patients has been
assessed in clinical trials. Still other compounds, i.e., CNI-1493, interleukin
11, tissue factor pathway inhibitors, and PGG-Glucan represent auspicious
immunomodulatory approaches for control of posttraumatic or postoperative
infections.
PMID- 9654319
TI - Hypovolemic shock in pediatric patients.
AB - Hypovolemic shock is a common disease treated in pediatric ICUs and emergency
departments worldwide. A wide variety of etiologic factors may cause this
disease, with the common net result of decreased intravascular volume leading to
decreased venous return to the heart and decreased stroke volume. Inadequate
perfusion results in impairment of delivery of nutrients and oxygen to vital end
organs. With the advent of pediatric critical care and pediatric emergency
medicine as specialties, deaths from hypovolemic shock have become increasingly
rare in the United States. The physical signs of hypovolemic shock in children
must be quickly recognized, and aggressive volume resuscitation must be
administered before irreversible end-organ dysfunction occurs. This is best
accomplished by large peripheral or central intravenous access, with intraosseous
access an alternative option in the pediatric patient. The amount as well as the
type of volume administered must be tailored for each individual patient, taking
into account the amount of intravascular depletion and the disease state in which
the shock has occurred. It is not uncommon for children to require large amounts
of fluid for resuscitation, and close attention must be paid to children with
fluid-refractory shock, who may require catecholamine and/or exogenous steroid
support in combination with aggressive fluid resuscitation.
PMID- 9654320
TI - Pathophysiology of cardiovascular dysfunction in septic shock.
AB - Sepsis and septic shock are common problems in the ICU and carry a very high
mortality. Myocardial depression is a common finding in patients with sepsis, and
is usually reversible as the patient recovers. Both exogenous mediators, such as
endotoxin, and endogenous cytokines, including tumor necrosis factor-alpha,
interleukin-1beta, and interleukin-6, have been implicated as important factors
in the pathophysiology of septic shock and the development of myocardial
depression in sepsis. Nitric oxide has also been implicated in the
pathophysiology of the cardiovascular response to sepsis. Better understanding of
the roles and interactions of these substances will be necessary to develop more
effective therapies without increasing morbidity and mortality.
PMID- 9654321
TI - Cardiogenic shock.
AB - The pathophysiology of cardiogenic shock in infants and children is
multifactorial and include noncardiac as well as cardiac etiologies, both
congenital and acquired heart disease. The management of patients in cardiogenic
shock requires a rational approach that is based upon the underlying
pathophysiology. The diagnosis and management of cardiogenic shock, therefore,
requires a thorough understanding of not only the underlying pathophysiology, but
also the diagnostic modalities used in making the diagnosis. In the pediatric
population, echocardiography plays a pivotal role in the diagnosis and management
of infants and children presenting with cardiogenic shock. In this article, the
pathophysiology of cardiogenic shock and the use of echocardiography in reaching
a differential diagnosis are discussed. In addition, the management of
cardiogenic shock is reviewed.
PMID- 9654322
TI - Hemorrhagic and obstructive shock in pediatric patients.
AB - Shock in childhood is most commonly related to injury and blood loss, but
hemodynamic compromise is occasionally caused by severe head or spinal injury,
tension pneumothorax, myocardial injury, arrhythmias, and sepsis. Regardless of
the cause, the initial management of the hypertensive child is establishment of a
secure airway, maintenance of ventilation, and initiation of volume replacement
via an adequate intravenous catheter. At the present time, crystalloid
resuscitation with lactated Ringer's solution and buffering of acidosis with
sodium bicarbonate is the standard approach, although in the future hypertonic
saline solution may play a role. Hemorrhage may be classified according to the
percentage of blood volume lost; losses in excess of 30% of blood volume (class
III and IV hemorrhage) usually require administration of packed red blood cells
and/or albumin as well. With appropriate management, the typical clinical signs
of shock will be reversed and the child will demonstrate improved vital signs,
peripheral circulation and sensorium, normalization of body temperature, reversal
of metabolic acidosis, and resumption of normal urine output. The more aggressive
the approach to resuscitation, the more prompt the patient's response and the
more likely morbidity and mortality will be minimized.
PMID- 9654323
TI - Linear and nonlinear dynamics and the pathophysiology of shock.
AB - Rapid progress has been made in the use of linear and nonlinear time series
analysis of heart rate and blood pressure variability as an indicator of disease
severity and prognosis for patients in shock. Clinical and experimental studies
have demonstrated the potential for linear and nonlinear measurements as a method
for quantifying changes in neuroautonomic cardiovascular regulatory mechanisms.
These measures have been demonstrated to correlate with severity of illness and
outcome for critically ill and injured patients, including those with shock.
These powerful mathematical techniques may allow for new insights into the
pathophysiology of shock. In addition, these measures may also enable detection
of early changes in neuroautonomic cardiovascular regulatory mechanisms during
the development of shock before the onset of overt hypotension and inadequate
tissue perfusion or may be used to assess the response to therapy. Further
studies are needed to establish the role of these tools in clinical use.
PMID- 9654324
TI - Reactive oxygen species in the cellular pathophysiology of shock.
AB - Reactive oxygen species (ROS) mediate the fine balance between cellular
physiology and pathophysiology. Accordingly it is not surprising that cellular
redox homeostasis is disrupted by shock events related to ischemia-reperfusion
and inflammation. ROS may initiate as well as amplify the shock cellular insult
in a number of ways which include important contributions to inflammation as well
as lytic and apoptotic cell death. In addition, ROS in the setting of shock
represent important antecedents to cellular proliferation, differentiation, and
adaptation by virtue of altered transcription and translation of antioxidant
enzymes, stress proteins, and a variety of cytokines. It is likely that an
eventual important biochemical therapeutic goal in the setting of shock will
involve re-establishing cellular redox homeostasis not only to ensure cellular
structural integrity, but also to re-establish normal secondary cellular signal
transduction mechanisms.
PMID- 9654325
TI - Molecular biology of septic shock.
AB - Septic shock is a complex pathophysiologic state which often leads to multiple
organ dysfunction, multiple organ failure, and death. This review summarizes
current views on the molecular biology of three aspects of septic shock:
recognition of bacterial invasion and induction of the cytokine response; genetic
variability among humans and their predispositions toward pathologic inflammatory
responses; and the signal transduction mechanisms which account for the transfer
of molecular signals from cytokine receptors on the plasma membrane to cytokine
responsive genes in the nucleus. In particular, the review summarizes the pathway
involved in tumor necrosis factor signaling through nuclear factor-kappaB, and
elucidates the molecular signals involved in inflammatory responses and
apoptosis.
PMID- 9654326
TI - Potential protective role of the heat shock response in sepsis.
AB - The heat shock response, a primitive and highly conserved cellular defense
mechanism, has broad protective effects against sepsis-induced injury. In various
models of sepsis, induction of the heat shock response protects against sepsis
induced mortality, organ injury, cardiovascular dysfunction, and apoptosis. The
mechanisms by which the heat shock response protects against sepsis-induced
injury are currently under investigation. One potential mechanism involves the
ability of the heat shock response to inhibit proinflammatory responses. The heat
shock response has been demonstrated to inhibit expression of the cytokines tumor
necrosis factor (TNF)-alpha and interleukin (IL)-1beta. The heat shock response
has also been demonstrated to inhibit cytokine-mediated expression of inducible
nitric oxide synthase. Recent studies demonstrated that the heat shock response
inhibits nuclear translocation of nuclear factor-kappaB (NF-kappaB), a
transcription factor involved in the regulation of many proinflammatory
responses. Heat shock response-mediated inhibition of NF-kappaB nuclear
translocation involves stabilization of an NF-kappaB inhibitory protein called I
kappaBalpha. The heat shock response also increases expression of I-kappaBalpha,
thus providing another potential mechanism by which the heat shock response can
modulate proinflammatory responses. Future studies designed to further understand
the protective role of the heat shock response against sepsis-induced injury may
allow for the development of rational pharmacologic agents or gene therapy
methods to safely induce the heat shock response as a strategy to treat patients
with sepsis.
PMID- 9654327
TI - Recent advances in pediatric cardiopulmonary resuscitation and advanced life
support.
AB - The end point of uncorrected shock is cardiac arrest. Once cardiac arrest occurs,
the outcome in children is typically poor, reflecting the fact that cardiac
arrest does not occur until the child's physiologic reserves are exhausted.
Despite more than 35 years of research in cardiac arrest, the optimal management
and treatment remain uncertain. The optimal method of basic and advanced life
support to restore cardiac function and preserve brain function is unclear, as is
the appropriate application of pharmacologic agents to restart the heart and
subsequently to manage postarrest shock. New techniques in basic life support
merit evaluation in children, particularly interposed abdominal compression and
active compression-decompression cardiopulmonary resuscitation. Epinephrine
remains the pharmacologic agent of choice. The role of bicarbonate in the
management of acidosis and the role of calcium in restarting the heart remain
controversial. If and when the heart is restarted following cardiac arrest, the
work is just beginning for the intensivist to manage the postarrest shock state.
Dobutamine is useful in the normotensive child while epinephrine infusions are
used to stabilize hypotensive, postarrest shock in the child.
PMID- 9654328
TI - Nutrition and shock in pediatric patients.
AB - Critically ill patients, including those in shock, often present with significant
metabolic derangement in protein and energy metabolism characterized by:
increased protein breakdown which is not suppressed by protein or energy intake;
reprioritization of protein synthesis with increased synthesis of acute-phase
proteins; decreased synthesis of structural proteins; and high protein turnover.
In addition, there is also glucose and lipid intolerance. Adequate nutritional
and metabolic support of the critically ill child under these conditions is a
challenging endeavor. Traditionally, critically ill children have received
nutritional requirements based on those of healthy children despite the fact that
the critically ill population is physiologically and metabolically different.
Furthermore, nutritional requirements in healthy children are largely based on
limited data. With emerging knowledge of non-nutritional functions of nutrients,
adequacy of nutritional support and requirements will eventually depend on the
goals to be achieved: nutritional, physiologic, and/or pharmacologic.
PMID- 9654329
TI - An international perspective on the treatment of pediatric shock: the Brazilian
experience.
AB - Shock in the pediatric population has many preventable causes. Treatment of
children in shock will depend on access to health services, training of health
personnel, availability of diagnostic procedures, monitoring, and therapeutic
measures. Countries will differ among themselves and within themselves in the
care provided to children developing shock. In Brazil, the majority of children
are cared for in public hospitals, which often lack resources for basic care.
Many children in shock do not even reach healthcare services. Investment in
training healthcare personnel in a simplified and systematic approach to shock
and access to equipped health services are basic to improved outcomes in the
treatment of pediatric shock. The Brazilian experience in the treatment of
children in shock outside hospital facilities, in the emergency department, and
in the ICU is described.
PMID- 9654330
TI - High ethanol tolerance in young adults is associated with the low-activity
variant of the promoter of the human serotonin transporter gene.
AB - Central serotonergic neurotransmission has been implicated in the aetiology of
ethanol tolerance and dependence. Cellular expression of the serotonin
transporter and serotonin reuptake is modulated via a polymorphic, repetitive
element in the 5'-flanking regulatory region of the serotonin transporter gene (5
HTTLPR). We report the association of the low-activity, short variant of the 5
HTTLPR with high ethanol tolerance among young adults in a case-control
association study (n = 713). The low-activity 5-HTTLPR showed a significantly
increased allele frequency (chi2 = 7.30; df = 2; P = 0.007) and genotype
frequency among young adults (< or =26 years) with high ethanol tolerance
homozygous for the short allele (chi2 = 7.58; df = 1; P = 0.02). The estimated
odds ratio for the homozygous short variant compared to the homozygous long
variant was 2.82 (95% CI 1.30-6.11). This indicates that the low-activity 5
HTTLPR may be involved in the neuronal mechanisms responsible for ethanol
tolerance and dependence.
PMID- 9654331
TI - Rat dorsal root ganglion neurones express different capsaicin-evoked Ca2+
transients and permeabilities to Mn2+.
AB - Capsaicin (1 microM) evoked [Ca2+]i transients in two-thirds of a Percoll
gradient enriched population of rat dorsal root ganglion (DRG) neurones. Amongst
the capsaicin-sensitive neurones, 68% responded to capsaicin with peak [Ca2+]i
transients of 681 +/- 67 nM, whereas the remaining neurones gave peak [Ca2+]i
transients of 260 +/- 84 nM. In the presence of Mn2+ in Ca2+-free medium,
capsaicin evoked quenching of fura-2 fluorescence, due to Mn2+ influx, in a
similar proportion of neurones. Two patterns of capsaicin-sensitive Mn2+
quenching were observed: 72% of neurones showed rapid quenching (t1/2 of 18.3 +/-
4.1 s), whereas the remaining neurones had low quenching rates (t1/2 of 119 +/-
33 s). Distinct capsaicin-sensitive subpopulations of DRG neurones can thus be
distinguished on the basis of their peak [Ca2+]i transient amplitudes, which
appear to be associated with different rates of Ca2+ influx.
PMID- 9654332
TI - Interactions between nociceptive and non-nociceptive afferent projections to
cerebral cortex in humans.
AB - We investigated the effect of a tonic discharge of muscle nociceptive afferents
on somatosensory evoked potentials (SEPs) in humans in response to stimulation of
non-nociceptive afferents arising from the same muscle. Conditioning nociceptive
muscle stimulation was achieved by local injection of 50 mg levo-ascorbic acid
(in a volume of 0.3 ml) in the body of the extensor digitorum brevis muscle
(EDB). The test stimulus for SEPs was an electrical pulse applied to the EDB
nerve at an intensity below the motor threshold. The main finding was that tonic
muscle nociceptive stimulation strongly depressed the middle-latency P60-N75
complex without modifying the size of the early P40-N50 complex of SEPs.
Depression of the P60-N75 complex was correlated with the pain-induced loss of
proprioception of the foot, making it plausible that this cortical complex
reflects neuronal processes leading to perception.
PMID- 9654333
TI - Differential uptake of dextran beads by astrocytes, macrophages and
oligodendrocytes in mixed glial-cell cultures from brains of neonatal rats.
AB - The present study addresses a controversy over the abilities of astrocytes to
perform phagocytosis. Primary glial-cell cultures were prepared from the brains
of neonatal rats and were incubated with fluorescently-labeled dextran beads
(molecular weights approximately 10 and approximately 40 kDa). Astrocytes and
oligodendrocytes were double-labeled by immunofluorescence staining of cell
specific markers, and microglia by lectin histochemistry. Cells were permitted to
take up beads for 1 h, fixed, and incubated with primary antibodies, followed by
fluorescent secondary antibodies or fluorescently-labeled lectin. Macrophages and
astrocytes internalized beads of both sizes. In astrocyte processes the beads
appeared to line up along glial filaments. The results, which provide direct
evidence for uptake of beads by astrocytes in vitro and against equally rapid, if
any, uptake by oligodendrocytes, bear upon issues of acid/base balance and glial
cell development and are relevant to neuropathological observations in human
disease.
PMID- 9654334
TI - Ontogeny of a diurnal rhythm in arylalkylamine-N-acetyltransferase mRNA in rat
pineal gland.
AB - Melatonin synthesis in the pineal gland of adult rats is linked to cAMP-dependent
transcriptional and post-transcriptional regulatory mechanisms affecting its rate
limiting enzyme, the arylalkylamine-N-acetyltransferase (AA-NAT). During
development of the pineal gland, neuronal control gains access to the earlier
matured cAMP-signaling pathway to shape the day-night rhythm in AA-NAT enzymatic
activity. By semiquantitative in situ hybridization we analyzed if the
developmental onset of a rhythmic AA-NAT activity is correlated to a temporally
parallel onset in AA-NAT transcription. We found that AA-NAT mRNA levels in rat
pineal gland become rhythmic at postnatal day 5. Thus, AA-NAT gene transcription
in rat pineal gland starts to show day-night differences shortly prior to the
appearance of a rhythmic AA-NAT activity.
PMID- 9654335
TI - Transient expression of the vesicular monoamine transporter during development in
the rat thalamus and cortex.
AB - The postnatal developmental pattern of the central vesicular monoamine
transporter-2 (VMAT2) was analyzed in the rat brain by means of quantitative
autoradiography with a specific and high affinity ligand [3H]dihydrotetrabenazine
([3H]TBZOH). We show a dense expression of VMAT2 in the cortex (especially area
17) and thalamus (particularly the dorsal lateral geniculate nucleus) at
postnatal days 1 and 8. This pattern of VMAT2 distribution was transient since it
was no longer observed at day 20 or in the adult rat brain where VMAT2 density
was weak and uniform in these regions. These data suggest that monoamine
vesicular storage participates in the early postnatal maturation of thalamus and
cortex.
PMID- 9654336
TI - Cannabinoid effects in basal ganglia in a rat model of Parkinson's disease.
AB - Cannabinoid receptors in the brain are highly concentrated in the basal ganglia,
which is in accordance with their well known effects on motor behavior. In this
study, rats with 6-hydroxydopamine lesions of the nigrostriatal pathway were
implanted with cannulae in the striatum, globus pallidus and substantia nigra.
The effect of unilateral infusion of the potent cannabinoid agonist CP55,940 on
turning behavior was studied for each structure. Lesioned animals responded to
intrapallidal and intrastriatal administration of the cannabinoid in a manner
that was similar to that of unlesioned animals. However, lesioned animals showed
greater contralateral turning in response to the cannabinoid infusions in the
substantia nigra than unlesioned animals.
PMID- 9654337
TI - Effects of neurotoxic doses of methamphetamine on potassium and amphetamine
evoked overflow of dopamine in the striatum of awake rats.
AB - The effects of neurotoxic doses of methamphetamine on basal and evoked overflow
of dopamine in the striatum were examined in awake rats using microdialysis. Male
Fischer-344 rats were administered methamphetamine (5 mg/kg s.c.) or saline four
times in 1 day at 2-h intervals. Microdialysis experiments were carried out 1
week later. Basal levels of dopamine, 3,4-dihydroxyphenylacetic acid, and
homovanillic acid were reduced in the striatum of the methamphetamine-treated
animals. Local application of excess potassium (100 mM) and amphetamine (100
microM), and intraperitoneal injection of amphetamine (1.5 mg/ kg), led to
increased levels of extracellular dopamine in the striatum of both
methamphetamine- and saline-treated rats. However, the increase was significantly
less in the methamphetamine-treated animals. Tissue levels of dopamine and
metabolites were reduced in the striata of rats treated with methamphetamine.
These results indicate that treatment with neurotoxic doses of methamphetamine
can lead to functional changes in dopamine release in the striatum of Fischer-344
rats.
PMID- 9654338
TI - Anatomy of a new paired tract of the pineal gland in humans.
AB - The human pineal gland and it anterior attachments were investigated grossly in
the fresh state and microscopically in the sagittal plane and 25 degrees
tangential to the coronal plane of sectioning. Fiber stains of tissue samples
from the midline commissural attachments of the pineal gland indicated the
presence of both myelinated and non-myelinated fibers connecting the pineal gland
and the pre-tectal area. A previously unreported paired fiber tract was observed
associated with the anterior inferio-ventro-lateral pineal gland. This paired
tract appears to be physically separate and distinct from the posterior
commissure. These tracts form a structural component of the wall of the pineal
recess. The fibers coursing in this paired tract are myelinated, and are of two
different sizes (1-3 microm diameter and 5-8 microm diameter) as determined by
electron microscopy. Fibers from these tracts invade the pineal gland, and can be
traced a short distance into the lateral pre-tectal area. The precise point of
origin and termination for this paired tract is unknown.
PMID- 9654339
TI - Intraseptal infusions of a low dose of AP5, a NMDA receptor antagonist, improves
memory in an object recognition task in rats.
AB - The present study describes the effects of intraseptal microinjections of 2 nmol
of AP5 upon memory of rats subjected to a two trial object recognition task. This
task allows us to detect either a disruption or an improvement of memory
according to the duration of the interval between the sample trial (T1) and the
choice trial (T2). AP5 injected before T1 did not disrupt memory in a schedule
able to detect an amnesia. In a schedule able to detect an improvement of memory,
AP5 injected either 10 min before or just after T1, or 10 min before T2, improved
retention. These results suggest that microinjection of a low dose of AP5 in the
septum improves the acquisition, the consolidation and the restitution of the
information in a working memory task.
PMID- 9654340
TI - Adenosine induces apoptosis by inhibiting mRNA and protein synthesis in chick
embryonic sympathetic neurons.
AB - Our previous work has established that adenosine is toxic to chick embryonic
sympathetic neurons and kills freshly plated neurons by a process of apoptosis.
Although the exact mechanism remains unknown, we found that phosphorylation of
adenosine was essential to the toxicity. Using markers for RNA ([3H]uridine) and
protein ([35S]methionine) synthesis we demonstrate here that in freshly plated
sympathetic neurons adenosine inhibits RNA and protein synthesis by about 50%.
The inhibitory effects of adenosine on RNA and protein synthesis, and increased
ATP synthesis were blocked by adenosine kinase inhibitor, suggesting that
phosphorylated products are responsible for inhibition of RNA and protein
synthesis and cell death. Adenosine-induced inhibition of RNA and protein
synthesis in neuronal cells provides a new role for adenosine in the regulation
of cell function.
PMID- 9654341
TI - GABAergic inhibition of neonatal rat phrenic motoneurons.
AB - Phrenic motoneurons (PMNs) receive intermittently glutaminergic inspiratory
drives and GABAergic inhibition in adult mammals. Since gamma-amino-butyric acid
(GABA) might act as an excitatory amino acid in early stages of development, we
here investigated if GABA(A) receptors inhibit PMNs in neonates. Using in vitro
neonatal rat brainstem-spinal cord preparation, local application of GABA and
muscimol (a GABA(A) receptor agonist) to the vicinity of PMNs consistently
reduced the inspiratory activity of C4 ventral roots. Under whole-cell patch
clamp conditions and in the presence of 0.5 microM TTX to block synaptic
transmission, muscimol (10 microM) decreased whole-cell input resistance, and
surprisingly, when PMNs were voltage-clamped at their resting membrane potential,
muscimol induced depolarizing-inward, rather than hyperpolarizing-outward
membrane current. Our findings indicate that GABA(A) receptors mediate a
depolarizing blockade of the glutaminergic excitatory inputs to neonatal rat
PMNs.
PMID- 9654342
TI - Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of
TRP, expressed in Xenopus oocytes.
AB - To elucidate whether rat transient receptor potential (TRP-R), a rat TRP4
homolog, functions as a store-operated Ca2+ channel (SOC), we have measured the
Ca2+ entry after thapsigargin treatment in Xenopus oocytes injected with mRNA for
TRP-R. While non-injected oocytes elicited an SOC response, significantly larger
responses were observed in the oocytes expressing TRP-R. The oocyte-native SOC
response was inhibited by injection of antisense oligodeoxyribonucleotide for
mammalian TRP1. When Ca2+ concentration-SOC response curve was examined, the EC50
value was much smaller in oocytes expressing TRP-R than that of non-injected
oocytes. These results suggest that TRP-R functions as SOC having higher
sensitivity to external Ca2+ than amphibian TRP1 channel.
PMID- 9654343
TI - NF-kappa B is activated and ICAM-1 gene expression is upregulated during
reoxygenation of human brain endothelial cells.
AB - Reperfusion injury is mediated, in part, by the upregulated expression of genes
in microvascular endothelial cells that encode for inflammatory cytokines and
adhesion molecules. The redox-regulated transcription factor, nuclear factor
kappa B (NF-kappaB), may play a major role in the induced expression of these
genes. In this study we use cultured human brain microvascular endothelial cells
(HBMEC) to investigate whether reoxygenation of hypoxic HBMEC results in the
activation of NF-kappaB and the upregulation of the adhesion molecule, ICAM-1.
When HBMEC were subjected to hypoxia followed by reoxygenation but not hypoxia
alone, an NF-kappaB complex composed of p65 and p50 Rel proteins was rapidly
activated within 15-30 min. Four hours later, expression of the ICAM-1 gene was
significantly upregulated. The antioxidant pyrrolidine dithiocarbamate and the
proteasome inhibitor, n-Tosyl-Phe-chloromethyl ketone, blocked both the
activation of NF-kappaB and the upregulation of the ICAM-1 gene. These results
indicate that NF-kappaB is activated in HBMEC by reoxygenation and may play a
significant role in the upregulation of the ICAM-1 gene. Agents which inhibit NF
kappaB activation may be potential therapeutic agents in acute ischemic stroke.
PMID- 9654344
TI - Entrainment of the medullary respiratory generators by electrical stimulation in
the cervical grey matter on in vitro preparations of newborn rat.
AB - The present study describes how the medullary respiratory generators (mRGs) can
be driven by periodic electrical stimulations applied to the ventral part of the
spinal grey matter at the C5 level. The general effect of an electrical stimulus
(5 pulses at 200 Hz and between 50 and 80 microA) was either to delay or to
advance the occurrence of the medullary respiratory burst via a resetting
process, depending on its time of application within the corresponding cycle.
Compared to the spontaneous medullary periods, the phase-response curves show
that the non-spontaneous medullary period increased progressively when the
electrical stimulus was applied within the first two-thirds of the corresponding
medullary cycle and decreased when it was applied within the last third of the
latter one. These curves were constructed in order to predict the limits of a
stable 1:1 entrainment. As predicted, the 1:1 entrainment was obtained when we
stimulated repetitively at resetting intensity within the frequency limits
determined by the phase-response curves. The entrainment became harmonic (2:1,
3:1, 4:1) when the stimulation frequency increased near submultiples of the
fundamental mRGs frequency. From these data, we conclude on the presence of
ascending connections from the C5 segment of the spinal cord which might be
involved in the realisation of the locomotor-respiratory coupling.
PMID- 9654345
TI - Kindling-induced neurogenesis in the dentate gyrus of the rat.
AB - Kindling, a form of neuronal plasticity produced by repeated low intensity
electrical brain stimulation, leads to epileptic seizures. To address possible
causes of this phenomenon, we have prepared amygdala-kindled animals and measured
neurogenesis, by bromodeoxyuridine incorporation. Early, when focal seizures were
present, there was no evidence of a change in the rate of hippocampal
neurogenesis. In contrast, during the later phases of kindling, when secondary
generalization was well established and motor seizures were present, neurogenesis
was enhanced by 75-140%, depending on the hippocampal region. Double labelling
with the neuron-specific marker TOAD-64 demonstrated the presence of numerous new
born granule neurons in the kindled animals. We propose that the newly-born
neurons contribute to the cellular changes and behavioral symptoms associated
with this type of epileptiform brain plasticity.
PMID- 9654346
TI - Lysophosphatidylserine potentiates nerve growth factor-induced differentiation of
PC12 cells.
AB - Since lysophosphatidylserine (LPS) is required for nerve growth factor (NGF)
induced secretion of histamine from rat mast cells, we investigated whether LPS
might potentiate the effects of NGF in inducing neural differentiation of PC12
cells. Cell morphology was evaluated 48 h after addition of NGF, LPS or NGF +
LPS. LPS alone was ineffective, but strongly promoted NGF-induced differentiation
to give rise to cells that more closely resembled neurons in primary culture. LPS
increased the number of PC12 cells that developed neurites in response to NGF
(0.01-40 ng/ml), with the response to 1.0 ng/ml increasing from 17.8 +/- 2.2 to
50.8 +/- 4.1% when LPS was also present. Neurite length was also greater in PC12
cells receiving NGF + LPS: 17.8 +/- 2.2% of cells had neurites longer than three
cell body diameters with 1.0 ng/ml NGF + 1 microg/ml LPS, compared to 1.6 +/-
1.6% with NGF alone. Further, cells responding to NGF + LPS typically developed
only 1-2 neurites per cell (90.9%, 1 microg/ml LPS), compared with the multipolar
appearance with NGF alone (71.1% with 3-6 neurites, 10 ng/ml NGF). LPS occurs at
sites of tissue damage where NGF can also be present, and therefore may be a
naturally-occurring modifier of neuronal structure and/or function.
PMID- 9654348
TI - Expression of beta-endorphin and its receptors in the spinal cord of obese
diabetic ob/ob mice.
AB - Immunocytochemistry was used to demonstrate the presence of beta-endorphin, and
quantitative autoradiography with [125I]beta-endorphin was used to study beta
endorphin binding sites, in spinal cord of lean and obese diabetic ob/ob mice.
The proportion of beta-endorphin-positive neurones was approximately 6-fold
higher in the ventral horn, and 2-fold higher in the dorsal horn of ob/ob mice
than in lean controls. The maximum density of beta-endorphin binding sites was
significantly higher in the dorsal horn and intermediate zone of ob/ob mice. The
Kd value for the binding was similar in the ventral horn and intermediate zone in
lean and ob/ob mice, but slightly lower in the dorsal horn of ob/ob mice. The
findings indicate upregulation of both beta-endorphin and its receptors in spinal
neurones of ob/ob mice.
PMID- 9654347
TI - Concurrent decrease of vasopressin and protein kinase Calpha immunoreactivity
during the light phase in the vole suprachiasmatic nucleus.
AB - Vasopressin (AVP) is a major neuropeptide in the suprachiasmatic nucleus, the
mammalian hypothalamic circadian pacemaker. Protein kinase Calpha is a putatively
coupled intracellular messenger. Mean numbers of AVP- and protein kinase Calpha
immunoreactive neurons were determined in the suprachiasmatic nucleus of common
voles, entrained to a 12:12 h light-dark (LD) cycle, at the beginning of the
light period (zeitgeber time zero) and 6 h later (zeitgeber time six). At
zeitgeber time zero, mean numbers of AVP- and protein kinase Calpha-
immunoreactive neurons were 2194 and 9897, respectively. Both numbers decreased
significantly with about 40% at zeitgeber time six. This concurrent decrease was
most pronounced in the dorsomedial aspect of the suprachiasmatic nucleus. These
findings are consistent with the findings of a peak of AVP release in rats during
the early light phase.
PMID- 9654349
TI - Peripheral fields of sympathetic vasoconstrictor neurons in guinea pigs.
AB - We have combined retrograde axonal tracing using Fast Blue and Dil, with
immunohistochemistry, to estimate the maximum size of peripheral fields of
identified sympathetic vasoconstrictor neurons projecting to guinea-pig ear tips.
Many neurons in the superior cervical ganglia were labelled with both Fast Blue
and Dil after dye injections up to 7 mm apart. Few neurons were labelled when dye
injections were 8-10 mm apart. Neurons labelled with both Dil and Fast Blue after
dye injections 5-7 mm apart had, on average, larger somata (436 +/- 84 microm2,
mean +/- SEM, n = 47) than neurons labelled with Dil only (388 +/- 11 microm2, n
= 147). Typically, 50-100 neurons innervated a region of vasculature 1 mm in
diameter. We conclude that sympathetic vasoconstrictor neurons branch widely
before converging on to their target blood vessels. Progressive recruitment of
vasoconstrictor neurons with increasing field size would provide an efficient
mechanism for graded neural control of the circulation.
PMID- 9654350
TI - Noradrenaline neurotoxin DSP-4 effects on sleep and brain temperature in the rat.
AB - N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has a selective degenerative
effect on noradrenergic fibers originating from locus coeruleus (LC) neurons. In
the present study, we studied its effect on vigilance states and brain
temperature by continuous recordings for periods of 1-5 days and 2-4 weeks
following DSP-4 treatment. On the first day, paradoxical sleep duration was
significantly decreased (-67%, P < 0.05), slow-wave sleep (SWS) duration
increased (+16%, P < 0.05) up to 48 h after DSP-4 treatment (+8%, P < 0.05) and
the wake period decreased (-8%, P < 0.05). The vigilance states returned to
control values 4-5 days later. The brain temperature was decreased during the
first night (-2 degrees C) and then recovered the control values. Two and 4 weeks
after DSP-4 treatment, paradoxical sleep was still decreased (-18% and -23%,
respectively, P < 0.05), while SWS was significantly increased only at night
during the fourth week (+23%, P < 0.05). These results therefore provide evidence
for a differential involvement of the noradrenergic LC system in sleep mechanisms
depending on the light-dark cycle. Different hypotheses are proposed.
PMID- 9654351
TI - Development of systemic lupus erythematosus in mice is associated with alteration
of neuropeptide concentrations in inflamed kidneys and immunoregulatory organs.
AB - In the present study we used a well-characterised model of murine lupus, the
female NZB/W hybrid, to study the possible involvement of neuropeptides in the
pathogenesis of systemic lupus erythematosus (SLE). Analysis of neuropeptides
with a possible role in inflammation showed that substance P (SP) calcitonin gene
related peptide (CGRP) and neuropeptide Y (NPY) are present in increased
quantities in the inflamed kidneys of SLE mice, confirming their involvement in
local inflammation, while there is a general reduction in the peptide
concentrations in the lymphoid organs of lupus mice, except for NPY. Our results
suggest that the altered neuropeptide concentrations observed in the SLE lymphoid
organs may be partly responsible for the altered immune response and contribute
to the development of autoimmune diseases.
PMID- 9654352
TI - Cysteine dioxygenase: regional expression of activity in rat brain.
AB - The levels of expression of cysteine dioxygenase (CDO) protein and activity were
investigated in nine functionally distinct regions of the rat brain before and
after induction with methionine by Western analysis and an activity assay.
Activity expression ranged from no activity in the brain-stem to high activity
expression in the olfactory bulb and basal ganglia. Upon exposure to 400 mg/l
methionine for 5 days, significant induction of expression was observed in the
basal ganglia, brain-stem, cerebellum, hippocampus, midbrain and olfactory bulb.
Protein expression appeared to correlate with activity expression when levels
before and after induction were compared. This non-uniformity of expression may
reflect different physiological functions of CDO in these areas.
PMID- 9654353
TI - Formation and sequence analysis of secretoneurin, a neuropeptide derived from
secretogranin II, in mammalian, bird, reptile, amphibian and fish brains.
AB - Secretoneurin is a recently-characterized neuropeptide derived from secretogranin
II, a protein belonging to the class of chromogranins. We investigated the
phylogeny of this peptide by immunoblotting and gel-filtration high performance
liquid chromatography followed by radioimmunoassay of brain extracts of various
species including chicken, lizard, frog and fish. In addition the amino acid
sequence of secretoneurin from pig, hamster, rabbit, guinea-pig and chicken was
established by reverse transcriptase polymerase chain reaction. Secretoneurin is
strongly conserved during evolution, it is not only expressed in various
mammalian species but found also in the brain of birds, reptiles, amphibians and
fish. In all these species a significant or near complete processing of
secretogranin II to secretoneurin was observed. These data provide significant
evidence for the neuropeptide nature of the novel functional peptide.
PMID- 9654354
TI - m-Calpain (calcium-activated neutral proteinase) in Alzheimer's disease brains.
AB - An antibody specific for the calpain isoform m-calpain was used to resolve
conflicting results from several studies on the possible role of m-calpain in the
pathogenesis of Alzheimer's disease (AD). Levels of the enzyme in both cytosolic
and membranous fractions of brain tissue were determined by Western blot
analysis. We also demonstrated changes in m-calpain molecules in AD brains using
high-resolution 2D gel electrophoresis (2DE). The levels of the m-calpain isoform
detected in the cytosolic fraction were significantly increased in AD brains when
compared with the levels in controls. On 2DE, m-calpain molecules resolved into
eight main spots. These spots were detected in AD brains as well as in control
brains, suggesting that the calpain molecule was not qualitatively changed in AD.
Quantitative analysis of the m-calpain spots on 2DE, on the other hand, indicated
that the ratio of the intensity of four protein spots in the acidic region to
that of the total spots was increased in AD brains.
PMID- 9654355
TI - Dependence of sympathetic vasomotor tone on bilateral inputs from the rostral
ventrolateral medulla in the rabbit: role of baroreceptor reflexes.
AB - A unilateral microinjection of muscimol into the pressor region in the rostral
ventrolateral medulla (RVLM) of anaesthetised baroreceptor-denervated rabbits
resulted in large and sustained decreases in mean arterial pressure, renal
sympathetic nerve activity and heart rate (maximal decreases of 41 +/- 4 mmHg, 64
+/- 3%, and 59 +/- 8 beats/min, respectively). Subsequently, muscimol
microinjection into the contralateral RVLM pressor region resulted in further but
much smaller decreases in these variables. In contrast, it is well established
that in baro-intact animals unilateral inactivation of the RVLM pressor region
has little effect on resting sympathetic activity or arterial pressure -
bilateral inactivation is required to produce large and sustained decreases. The
results of the present study indicate that the baroreceptor reflex plays a
crucial role in maintaining resting sympathetic vasomotor activity under
circumstances in which the activity of RVLM presympathetic neurons is partially
impaired.
PMID- 9654356
TI - Prepulse facilitation of auditory startle response in hamsters.
AB - A visual prepulse was applied just before a burst of white noise with various
lead intervals ranging from 50 to 400 ms in hamsters. After habituation each
hamster received 120 trials of the auditory noise with or without the prepulse.
Amplitude of startle response increased significantly at 100 ms and 200 ms (n =
10). This enhancement disappeared in blind controls (n = 6). The amplitude of
startle response decreased during exploratory behavior, grooming, sniffing or
other movements. However, the facilitatory effects of the visual prepulse were
consistent, regardless of the animal's behavioral states, except sniffing. The
authors conclude that visual prepulse task is useful for studying the ability to
detect visual signals in hamsters, and that further study is necessary to
elucidate the factors affecting the enhancement of startle response in hamsters.
PMID- 9654357
TI - Biphasic effect of aluminium on cholinergic enzyme of rat brain.
AB - The cholinotoxic effect of aluminium has been widely reported. In vitro aluminium
has a biphasic effect on acetylcholinesterase activity. The present study
analyses its in vivo effect in brain regions. Rats were exposed to aluminium
chloride by the oral route at a dose of 320 mg/kg body weight for shorter (4 and
14 days) and longer (60 days) duration. Acetylcholinesterase activity in
olfactory bulb, striatum and hypothalamus brain regions increased after 4 and 14
days and decreased after 60 days of aluminium exposure. Aluminium level in the
brain regions studied increased significantly. No significant change in body
weight of rats exposed to aluminium was found. The biphasic change in
acetylcholinesterase activity may be due to slow accumulation of aluminium in the
brain regions and its effect on the enzyme.
PMID- 9654358
TI - Sevoflurane suppresses behavioral response in the rat formalin test: combination
with intrathecal lidocaine produced profound suppression of the response.
AB - We investigated the effects of intrathecal (i.t.) lidocaine, inhalation
sevoflurane, and a combination of i.t. lidocaine and sevoflurane on the formalin
test in rats. Group 1 (control) received i.t. saline 10 microl. Groups 2 and 3
received i.t. lidocaine 200 microg and 400 microg, respectively. Groups 4-6
received 1.2%, 2.4% and 3.6% sevoflurane, respectively. Interaction of drugs was
analyzed using a dose addition model. Group 7 received i.t. lidocaine 200 microg
and 1.2% sevoflurane. The biphasic behavioral activity of the hindpaw of rats was
observed. This study showed that i.t. lidocaine or inhalation sevoflurane before
formalin injection, significantly suppressed the behavioral activity of the
hindpaw of rats, and that this suppression was significantly potentiated by the
co-administration of i.t. lidocaine and inhalation sevoflurane.
PMID- 9654359
TI - Nitric oxide activates Ca2+-activated K+ channels in cultured bovine adrenal
chromaffin cells.
AB - The effects of sodium nitroprusside (SNP) on Ca2+-dependent K+ (KCa) channels in
cultured bovine adrenal chromaffin cells were investigated using single channel
recording patch-clamp techniques. KCa channels were activated by application of
100 microM SNP to the extracellular side of cell-attached patches. Methylene blue
(300 microM), an inhibitor of soluble guanylate cyclase, or H-8 (1 microM), a
protein kinase inhibitor with relative specificity for cGMP-dependent protein
kinase, diminished but did not completely abolish the SNP-induced KCa channel
activation. Diethylamine/NO complex (DEA/NO), an NO donor, also activated KCa
channels in cell-attached patches. Furthermore, application of 100 microM SNP or
100 nM DEA/NO to the intracellular surface of excised inside-out patches also
activated KCa channels in the bath solution which contained 1 microM Ca2+. These
results indicate that SNP is capable of activating the KCa channel via cGMP
dependent and -independent mechanisms. These studies demonstrate that NO may
serve as an important regulatory mechanism for catecholamine secretion in
chromaffin cells via the activation of KCa channels.
PMID- 9654360
TI - ATP produces potassium currents via P3 purinoceptor in the follicle cell layer of
Xenopus oocytes.
AB - Purinoceptor agonists produced potassium currents with the order of potency: ATP
> adenosine = ADP = AMP > beta,gamma-methylene ATP, while a small response or no
response was induced by 2-methylthio ATP, UTP, or alpha,beta-methylene ATP. The
response induced by beta,gamma-methylene ATP was completely inhibited in the
presence of alpha,beta-methylene ATP, suggesting that the relevant receptor for
these agonists was a P3 purinoceptor. ATP induced currents with a latency of 24 s
and the currents were not induced in defolliculated oocytes. The currents were
not affected by either the Gi/o-protein inhibitor, pertussis toxin (PTX), or the
selective cAMP-dependent protein kinase inhibitor, H-89, or the phospholipase C
(PLC) inhibitor, neomycin, or the phospholipase A2 (PLA2) inhibitor, 4
bromophenacyl bromide. The currents were enhanced by the selective protein kinase
C (PKC) inhibitor, GF109203X, but otherwise, they were reduced by the potent PKC
activator, 12-O-tetradecanoylphorbol-13-acetate. The results of the present study
suggest that a P3 purinoceptor in the follicle cell layer of oocytes is involved
in activation of potassium channels and that the evoked currents are regulated by
PLC/PLA2-independent PKC activation.
PMID- 9654361
TI - Polyethylene glycol-induced hypovolemia affects the expression of MCH mRNA, but
not dynorphin or secretogranin II mRNAs, in the rat lateral hypothalamus.
AB - Two prominent neuron populations of the rat lateral hypothalamus express genes
encoding respectively the prepromelanin-concentrating hormone (MCH) or dynorphin
(DYN) and secretogranin II (SGII). Their roles remain hypothetical in mammals. In
the present study, we examined the changes in MCH, DYN and SGII gene expression
in dehydrated rats compared to controls. Dehydration was obtained by subcutaneous
injection of polyethylene glycol (PEG) resulting in a large reduction of the
extracellular fluid volume. Using competitive semi-quantitative RT-PCR and in
situ hybridization methods, PEG-injected animals showed a significant increase of
MCH mRNA level but no variation of DYN and SGII mRNA levels. These results
confirm previous observations suggesting that intra- and extracellular
dehydration challenges affect different regulation circuits; they indicate that
both neuron populations could be involved in the maintenance of body fluid
homeostasis, directly, or indirectly, as integrators of various information
leading to goal-oriented behaviour.
PMID- 9654362
TI - GABA(b) receptors differentially regulate hippocampal CA1 excitatory synaptic
transmission across postnatal development in the rat.
AB - Depression of excitatory postsynaptic potentials (EPSPs) by the GABA(b) agonist,
baclofen, was compared in hippocampal slices from juvenile (postnatal day (P) 15
21) and young adult (P28-35) rats. EPSP inhibition following baclofen application
was not different between age groups, however, paired-pulse facilitation (PPF)
increased more in young adults relative to juveniles. The differential effect of
baclofen on PPF was not due to tonic receptor activity, since the GABA(b)
antagonist, saclofen, did not differentially modify PPF. The baclofen-mediated
increase in PPF for juvenile slices could be enhanced by first increasing
transmitter release through an increased bath Ca2+ concentration. These findings
suggests that ligand-mediated presynaptic depression is inversely related to the
level of transmitter release and maturation of presynaptic inhibition is related
to development of release.
PMID- 9654363
TI - Regulation of the phosphorylation of glial fibrillary acidic protein (GFAP) by
glutamate and calcium ions in slices of immature rat spinal cord: comparison with
immature hippocampus.
AB - The effect of glutamate and lack of external Ca2+ on the phosphorylation of the
astrocyte cell marker glial fibrillary acidic protein (GFAP) was studied in
slices of hippocampus and thoracic spinal cord from immature (P12-16) rats.
Confirming previous work with immature hippocampal slices (Wofchuk, S.T. and
Rodnight, R., Neurochem. Int., 24 (1994) 517-523; Wofchuk, S.T. and Rodnight, R.,
Dev. Brain Res., 85 (1995) 181-186), glutamate strongly stimulated GFAP
phosphorylation in media with Ca2+ and in media lacking Ca2+ a quantitatively
similar stimulation of basal GFAP phosphorylation was observed. By contrast in
slices of immature thoracic spinal cord, glutamate had no effect on GFAP
phosphorylation and in media lacking Ca2+ phosphorylation of GFAP was inhibited.
Since GFAP phosphorylation is Ca2+-dependent and is not stimulated by glutamate
in slices of adult hippocampus, the present results suggest that astrocytic
functions in the rat spinal cord mature more rapidly than in the hippocampus. The
possibility that the difference in the control of GFAP phosphorylation in the two
structures is related to differences in the control of GFAP dephosphorylation was
investigated by incubating spinal cord slices with the calcineurin inhibitor
FK506 in the presence of Ca2+. In contrast to results obtained with hippocampal
slices FK506 had no effect on the phosphorylation state of GFAP in spinal cord
slices.
PMID- 9654364
TI - Central administration of urocortin inhibits vasopressin release in conscious
rats.
AB - Urocortin (UCN) is a new mammalian member of the corticotropin releasing factor
(CRF) family and supposed to be an endogenous ligand for type 2 CRF receptors.
Previous studies have revealed that UCN mRNA exists in the supraoptic nucleus
(SON), and that water deprivation increases UCN immunoreactivity in SON. In this
study, we examined the effect of centrally-administered UCN on arginine
vasopressin (AVP) release in conscious rats. Intracerebroventricular (i.c.v.)
injection of UCN (5.0 microg/rat) significantly attenuated AVP release induced by
hyperosmolality at 30 min after the injection. In contrast, CRF (5.0 microg/rat)
injected i.c.v. had no significant effect on AVP release. These results suggest
that central UCN play an inhibitory role in osmoregulation of AVP release.
PMID- 9654365
TI - Epitope specificity of a monoclonal antibody generated against the dissociated
CFA/I fimbriae of enterotoxigenic Escherichia coli.
AB - A monoclonal antibody (MAb 84) raised against the dissociated CFA/I fimbriae of
enterotoxigenic Escherichia coli was characterized with regard to antigen binding
and epitope specificity. Enzyme-linked immunosorbent assay (ELISA) showed that
MAb 84 had higher affinity to CFA/I subunits than to intact CFA/I fimbriae and
recognized a Salmonella flagellin carrying an insert corresponding to amino acids
32 to 45 of the CFA/I subunit. Fine epitope mapping based on the Pepscan
technique showed that the peptide 39TFESY43, derived from the sequence of the
mature CFA/I subunit, was specifically recognized by MAb 84. The 39TFESY43
sequence is probably not accessible on the surface of the native CFA/I fimbriae
since MAb 84 did not bind to intact fimbriae as evaluated in inhibition ELISA
tests. Moreover, MAb 84 did not agglutinate fimbriated ETEC cells nor inhibit
CFA/I-mediated hemagglutination or the adhesion to Caco-2 cells.
PMID- 9654366
TI - Culture supernatants of Lactobacillus acidophilus and Bifidobacterium
adolescentis repress ileal ulcer formation in rats treated with a nonsteroidal
antiinflammatory drug by suppressing unbalanced growth of aerobic bacteria and
lipid peroxidation.
AB - A nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4
methylsulfonylphenyl) thiophene (BFMeT), induced ileal ulcers in rats after oral
administration, while no ulcers were observed after subcutaneous injection. The
ileal ulcer formation in BFMeT-treated rats was examined to correlate the
administration of cultures of Lactobacillus acidophilus or Bifidobacterium
adolescentis with intestinal bacteria in the ileal contents and lipid
peroxidation of the small intestinal mucosa. Ileal ulcers were observed in more
than 85% of the rats treated with BFMeT at a dose of 1,000 mg/kg when they were
given tap water as drinking water. The incidence of ulcer formation was repressed
by giving culture supernatants of L. acidophilus or B. adolescentis as drinking
water, but not by giving the cell suspension as drinking water. Gram staining of
the ileal contents of normal rats revealed that 97% of the stained bacteria were
gram-positive rods and only 1.5% were gram-negative rods. The percentage of gram
negative rods 72 hr after BFMeT administration was 49.8% and increased over 30
fold in BFMeT-treated rats. However, the percentage of gram-negative rods was 9.7
% or 16%, respectively, in rats taking culture supernatants of L acidophilus or
B. adolescentis. In addition, thiobarbituric acid-reactive substances in the
ileal mucosa increased significantly in the rats given tap water for 72 hr after
BFMeT treatment, but not in rats given the culture supernatants of L. acidophilus
or B. adolescentis. Since BFMeT induced an unbalanced intestinal microflora, the
effect of antibiotic treatment on ulcer formation in rats was examined. The
magnitude of the ulcer formation in the antibiotic-treated rats was, in
decreasing order, metronidazole >none > kanamycin > a mixture (bacitracin,
neomycin and streptomycin). These results suggest that the intestinal microflora
plays an important role in ulcer formation and that a metabolite(s) of L.
acidophilus and B. adolescentis inhibits ileal ulcer formation by repressing
changes in the intestinal microflora and lipid peroxidation in BFMeT-treated
rats.
PMID- 9654367
TI - Cellular reaction to Mycobacterium avium complex (MAC) clinical isolates
differing in hemolytic activity and virulence for C57BL/6 mice.
AB - In this study we showed that Mycobacterium avium complex (MAC) clinical isolates
differed by the expression of hemolytic activity. Two hemolytic MAC strains were
less susceptible to the mycobactericidal effect of murine macrophages than two
unhemolytic MAC isolates. In vivo, hemolytic MAC bacilli survived in the spleens
of infected mice for a longer time than unhemolytic MAC strains. This suggested a
role of hemolysins in the virulence of MAC strains. There was no difference in
the cytotoxicity of T cells from mice immunized with M. bovis BCG towards
macrophages infected in vitro with MAC strains expressing or not expressing
hemolytic activity.
PMID- 9654368
TI - Morphological alterations of Saccharomyces cerevisiae induced by benanomicin A,
an antifungal antibiotic with mannan affinity.
AB - The effects of benanomicin A, a mannose-binding antifungal antibiotic, on yeast
cells of Saccharomyces cerevisiae were studied by electron microscopy.
Cytological studies using vital stain with methylene blue demonstrated that
benanomicin A at 20 and 80 microg/ml killed buds in preference to parent cells.
In confirmation, examination by TEM revealed that benanomicin A at 80 microg/ml
damaged buds more severely than parent cells. The major effect on the
ultrastructure was characterized by severe damage to the cell membrane. In
addition, it caused expansion and vacuolation of the endoplasmic reticulum (ER),
and partial fragmentation and disappearance of nuclear membranes. The membrane
disruptive activity of benanomicin A may be closely associated with its membrane
affinity.
PMID- 9654369
TI - Detection of verotoxin-producing Escherichia coli O157:H7 by multiplex polymerase
chain reaction.
AB - We constructed primers for multiplex polymerase chain reaction (PCR) to detect
verotoxin-producing Escherichia coli (VTEC) O157:H7. The multiplex PCR primers
were designed from the sequence of the flagellin structural gene of Escherichia
coli flagellar type H7 (GenBank under accession number L07388), and from the
sequence of the rfbE gene of Escherichia coli O157:H7 (GenBank under accession
number S83460). In addition to these primers, we used a primer pair reported by
Karch and Meyer (J. Clin. Microbiol. 27: 2751-2757, 1989) to amplify various VT
genes from VTEC. All of the examined specimens (18 isolates) of VT-producing E.
coli O157:H7 showed a positive result by the multiplex PCR test with the three
sets of primers. The sensitivity of detection for VT-producing E. coli O157:H7
was shown to be at least 3,000 cells per PCR tube.
PMID- 9654370
TI - Requirement of cauliflower mosaic virus open reading frame VI product for viral
gene expression and multiplication in turnip protoplasts.
AB - Cauliflower mosaic virus (CaMV) open reading frame (ORF) VI product (P6) has been
shown to be the major constituent of viral inclusion body, to function as a post
transcriptional transactivator, and to be essential for infectivity on whole
plants. Although these findings suggest that P6 has an important role in viral
multiplication, it is unknown whether P6 is required for viral multiplication in
a single cell. To address this question, we transfected turnip protoplasts with
an ORF VI frame-shift (4 bp deletion) mutant (pCaFS6) of an infectious CaMV DNA
clone (pCa122). The mutant was uninfectious. Co-transfection of plasmids
expressing P6 complemented the mutant. Overexpression of P6 elevated the
infection rate in co-transfection experiments with either pCa122 or pCaFS6. This
would have been achieved by elevating the level of pregenomic 35S RNA, a putative
polycistronic mRNA for ORFs I, II, III, IV and V, and by enhancing the
accumulation of these five viral gene products. When CaMV ORFs I, II, III, IV and
V were expressed from monocistronic constructs in which each of the ORFs was
placed just downstream of the 35S promoter, the accumulation of ORF III, IV and V
products depended on the co-expression of P6. The accumulation of ORF I and II
products was not detected, even in the presence of P6. These results suggest that
P6 is involved in the stabilization of other viral gene products as well as in
the activation of viral gene expression, and thus, is a prerequisite for CaMV
multiplication.
PMID- 9654371
TI - Serological differentiation between HCV subtypes 1a and 1b by a recombinant
immunoblot assay.
AB - Until now, no serological assay has been available for the differentiation of HCV
subtypes. Since there is evidence that the subtypes differently influence the
clinical course of HCV infection and the outcome of interferon therapy, we
established a strip immunoblot assay (NS-4 IBA) with recombinant HCV proteins of
the nonstructural 4 (NS-4) region propagated in Escherichia coli. Using this NS-4
IBA, we were able to distinguish HCV subtypes 1a and 1b, which are the most
prevalent subtypes in Europe and the U.S.A. The results of the serotyping assay
were compared with those obtained by nucleotide sequencing from the NS-5 region.
Concordant results were observed to match 94.9% (n=100) by the NS-4 IBA and
nucleotide sequencing. Discrepant results were obtained in only 5.1% (n=6). These
data indicate that HCV subtypes can be serologically distinguished, providing the
possibility for easier identification of infection with different HCV subtypes.
PMID- 9654372
TI - Measurement of arginine carboxypeptidase-generating activity of adult plasma.
AB - Arginine carboxypeptidase (CPR) is a novel carboxypeptidase which was first
described by Campbell and Okada. CPR is generated from a stable precursor of CPR
(proCPR) during coagulation or under other circumstances and is promptly
inactivated at 37 C. Therefore, it is not easy to determine CPR in blood samples.
Since proCPR can be separated from the other basic carboxypeptidase
(carboxypeptidase N; CPN) by passing plasma through DEAE gel, we have established
a method to determine the amount of proCPR after converting it to active CPR by
trypsin treatment. We first separated the proCPR from CPN using a filter cup tube
(FC tube) packed with DEAE Sephadex, and measured activity after conversion of
the enzyme to its active form using trypsin. With this method, no significant
decrease in proCPR was noted in the plasma of patients including those with
rheumatoid arthritis (RA), although CPR activity in fresh sera has been reported
to be decreased. This discrepancy suggests that proCPR is not depleted in most
patient sera, but that the level of activity of the enzyme which converts proCPR
into active CPR may be compromised in RA patients.
PMID- 9654373
TI - Regulation of promoter and intron enhancer activity in immunoglobulin heavy-chain
genes during B-cell differentiation.
AB - Chloramphenicol acetyltransferase (CAT) transgenic mice, in which the transgene
is regulated by the VH promoter and heavy-chain intron enhancer (E mu), were
examined to investigate the variation of activity of these cis-acting elements
during the late stage of B-cell development. CAT enzyme activity decreased when
resting B cells were stimulated through B-cell receptors (BCR) with goat anti
mouse IgM antibodies in vitro. On the other hand, when these B cells were
stimulated by lipopolysaccharide (LPS) in vitro, they showed enhanced CAT
activity, accompanied by an increase in the number of CD43+ B220+ cells (pro
plasma and plasma cells). In addition, the CAT activities in CD43+ B220+ and
PNAhi B220+ cells from immunized mice were higher than those in CD43- B220+ and
PNAlo B220+ cells, respectively. These results suggest that the activity of E mu
in the context of VH promoter was transiently down-regulated by stimulation
through the BCR but enhanced at the pro-plasma and plasma stages.
PMID- 9654374
TI - Occurrence of coagulase serotype among Staphylococcus aureus strains isolated
from healthy individuals--special reference to correlation with size of protein-A
gene--.
AB - One-hundred-and-nineteen strains of Staphylococcus aureus isolated from healthy
individuals for 3 years between 1991 and 1993 were subjected to an investigation
on the producibility of proteins including protein A, coagulase, enterotoxins and
toxic-shock syndrome toxin-1. Especially, protein A was the center of our
interest. Among these strains, 69, 43, 3 and 1 strains were found to have the
protein-A gene containing 5, 4, 3 and 2 IgG-binding domains, respectively. On the
other hand, only one strain was devoid of the protein-A gene. There were some
differences in the profile of the coagulase serotype between the group with 4 IgG
binding domains and that with 5 IgG-binding domains. Differences in the profile
of toxin production were also observed between the two groups.
PMID- 9654375
TI - Differentiation of Chlamydia species by combined use of polymerase chain reaction
and restriction endonuclease analysis.
AB - To differentiate Chlamydia spp., a primer pair designed to generate a genus
specific region of the major outer membrane protein (MOMP) gene was used in a PCR
to amplify a single DNA fragment of 245-259 bp. In the PCR, the expected single
DNA fragment was amplified from strains of Chlamydia trachomatis, C. psittaci, C.
pneumoniae and C. pecorum, respectively. By restriction endonuclease analysis
with AluI and PvuII, the amplified products exhibited four distinct patterns,
corresponding to the four species. It is, therefore, concluded that one-step PCR
followed by restriction endonuclease analysis as described in this study could be
a valuable method for the detection and differentiation of Chlamydia species.
PMID- 9654376
TI - Seeking order in disorder: computational studies of neurologic and psychiatric
diseases.
PMID- 9654377
TI - Methodology and validity in the construction of computational models of cognitive
deficits following brain damage.
AB - Over recent years, neural network models of several cognitive neuropsychological
disorders have been developed. These include word recognition difficulties, face
recognition difficulties, attentional deficits, visual processing impairments,
semantic deficits, and aphasia. These models are useful in various ways. Firstly,
they require detailed specifications of theories, and can focus attention on
critical assumptions. Secondly, they can query alternative theories, and provide
predictions which can be verified by testing patients. In this paper, issues
relating both to the methodology and validity of attempts to model cognitive
deficits using neural networks will be discussed, providing examples from several
studies. Issues discussed will include the requirement for models to perform
normally prior to damage, and to show potential effects of rehabilitation or
partial recovery following damage. A single model should be able to incorporate
multiple symptoms of a deficit and ideally also multiple syndromes when different
lesions are introduced. The model must also be able to handle variability between
patients with the same syndrome, and even with the same patient at different test
sessions.
PMID- 9654378
TI - Striatal mechanisms in Parkinson's disease: new insights from computer modeling.
AB - We review data and hypotheses concerning the functional anatomy of the striatum
and the role of its corticostriatal and nigrostriatal afferents in Parkinson's
disease (PD). Starting from molecular mechanisms of glutamatergic and
dopaminergic actions in the striatum we have developed a compartmental model of
striatal principal neurons that displays a significant degree of biological
realism. Simulations of a network of striatal projection neurons under conditions
likely to be found in healthy subjects as well as untreated and therapeutic
situations of advanced PD provide clues concerning the dynamics of neuronal
interactions and their possible effects on downstream motor structures in the
generation of positive and negative motor symptoms. We present tentative
biological explanations of the symptoms of rigidity and akinesia in PD leading to
predictions concerning the origin of abnormal movements and the beneficial
effects of dopaminergic treatment. Although these attempts are not yet sufficient
to account for the complexity of clinical symptoms found in PD they can guide
further empirical research and foster fruitful interactions between
experimentalists, theoreticians, and clinicians in unraveling the functional
anatomy of the basal ganglia.
PMID- 9654379
TI - Neural dynamics of short and medium-term motor control effects of levodopa
therapy in Parkinson's disease.
AB - A neural network model of movement control in normal and Parkinson's disease (PD)
conditions is proposed to simulate the time-varying dose-response relationship
underlying the effects of levodopa on movement amplitude and movement duration in
PD patients. Short and long-term dynamics of cell activations and
neurotransmitter mechanisms underlying the differential expression of
neuropeptide messenger RNA within the basal ganglia striatum are modeled to
provide a mechanistic account for the effects of levodopa medication on motor
performance (e.g. the pharmacodynamics). Experimental and neural network
simulation data suggest that levodopa therapy in Parkinson's disease has
differential effects on cell activities, striatal neuropeptides, and motor
behavior. In particular, it is shown how dopamine depletion in the striatum may
modulate differentially the level of substance P and enkephalin messenger RNA in
the direct and indirect basal ganglia pathways. This dissociation in the
magnitude and timing of peptide expression causes an imbalance in the opponently
organized basal ganglia pathways which results in Parkinsonian motor deficits.
The model is validated with experimental data obtained from handwriting movements
performed by PD subjects before and after medication intake. The results suggest
that fine motor control analysis and network modeling of the effects of dopamine
in motor control are useful tools in drug development and in the optimization of
pharmacological therapy in PD patients.
PMID- 9654380
TI - Computer models of hippocampal circuit changes of the kindling model of epilepsy.
AB - Abnormalities in the organization of brain circuits may underlie many types of
epilepsy. This hypothesis can best be evaluated in the case of temporal lobe
epilepsy, where evidence of rewiring (synaptic reorganization) can be found in
the dentate gyrus. Computer modeling of normal and reorganized dentate gyrus was
used to understand the functional consequences of these structural changes.
Hyperexcitability appeared to be largely limited by the powerful intrinsic
adaptation characteristic of granule cells, the principal cells in this area.
Combining disinhibition with new recurrent excitatory circuitry was necessary to
produce repeated firing of these cells. Paradoxically, continuing regenerative
activity was only seen with a large reduction in the strength of the inciting
stimulus. Validation of these findings will require further physiological
correlation.
PMID- 9654381
TI - Neuromodulatory control of hippocampal function: towards a model of Alzheimer's
disease.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder of cognitive
function whose cellular pathology and molecular etiology have been increasingly
and dramatically unraveled over the last several years. Despite this substantial
knowledge base, the disease remains poorly understood due to a basic lack of
understanding of how memories are stored and recalled in the brain. We describe a
preliminary attempt at constructing a detailed model of these basic neural
mechanisms; in particular, the natural dynamics of neuronal activity in
hippocampal region CA3 and the modulation and control of these dynamics by
subcortical cholinergic and GABAergic input to the hippocampus. We view the
construction of such a model, with sufficient detail at the cellular and
subcellular level, to be a necessary first step in understanding the effect of AD
pathology on the functional behavior of the underlying neural circuitry. The
network is based on the 66-compartment hippocampal pyramidal cell model of Traub
and colleagues and their 51-compartment interneuron interconnected with realistic
AMPA-, NMDA-, and GABA(A)-mediated synapses. Traub and others have shown that a
network composed of these modeled cells is capable of synchronization in the
gamma frequency range. We demonstrate here that this synchronization mechanism
can implement an attractor-based autoassociative memory. A new input pattern
arrives at the beginning of each theta cycle (comprised of 5-10 gamma cycles),
and the pattern of activity across the network converges, over several gamma
cycles, to a stable attractor that represents the stored memory. In this model,
cholinergic deprivation, one of the hallmarks of AD, leads to a slowing of the
gamma frequency which reduces the number of "cycles" available to reach an
attractor state. We suggest that this may be one mechanism underlying the memory
loss and cognitive slowing seen in AD. Our results also support the idea that
acetylcholine acts on individual neurons to induce and maintain a transition from
intrinsic bursting to spiking in pyramidal cells. These results are consistent
with the hypothesis that spiking and bursting in CA3 pyramidal cells mediate
separate behavioral functions, and that cholinergic input is required for the
transition to and support of behavioral states associated with the online
processing and recall of information.
PMID- 9654382
TI - An artificial neural network simulating performance of normal subjects and
schizophrenics on the Wisconsin Card Sorting Test.
AB - Mental diseases such as schizophrenia are being modeled by artificial neural
networks in an attempt to understand the underlying neuropathological processes.
We studied hospitalized psychiatric patients that met the DSM-IIIR criteria for
schizophrenia (N=19), and normal subjects with no psychiatric history (N=18).
Performance on the Wisconsin Card Sorting Test (WCST) by schizophrenic patients
was poorer than normal subjects as estimated by various scoring measurements. We
then modeled an artificial neural network, motivated by biological
considerations, that is able to simulate performance of normals and
schizophrenics on the WCST. In order to model the complex nature of the WCST, we
designed novel learning rules based on non-associative learning paradigms. We
found that there must be a minimum amount of noise, or inherent synaptic
instability, for our model to perform similar to schizophrenics.
PMID- 9654383
TI - Adenovirus in the brain: recent advances of gene therapy for neurodegenerative
diseases.
AB - Adenovirus is an efficient vector for neuronal gene therapy due to its ability to
infect post-mitotic cells, its high efficacy of cell transduction and its low
pathogenicity. Recombinant adenoviruses encoding for therapeutical agents can be
delivered in vivo after direct intracerebral injection into specific brain areas.
They can be transported in a retrograde manner from the injection site to the
projection cell bodies offering promising applications for the specific targeting
of selected neuronal populations not easily accessible by direct injection, such
as the motor neurons in the spinal cord. Adenoviral vectors are also efficient
tools for the ex vivo gene therapy, that is, the genetical modification of cells
prior to their transplantation into the nervous system. Recently, the efficacy of
the adenovirus as a gene vector system has been demonstrated in several models of
neurodegenerative diseases including Parkinson's disease (PD) and motor neuron
diseases. In rat models of PD, adenoviruses encoding for either tyrosine
hydroxylase, superoxide dismutase or glial-derived neurotrophic factor improved
the survival and the functional efficacy of dopaminergic cells. Similarly, the
intramuscular injection of an adenovirus encoding for neurotrophin-3 had
substantial therapeutic effects in a mutant mouse model of motor neuron
degenerative disease. However, although adenoviruses are highly attractive for
neuronal gene transfer, they can trigger a strong inflammatory reaction leading
in particular to the destruction of infected cells. The recent development of new
generations of adenoviral vectors could shed light on the nature of the immune
reaction caused by adenoviral vectors in the brain. The use of these new vectors,
combined with that of neurospecific and regulatable promoters, should improve
adenovirus gene transfer into the central nervous system.
PMID- 9654384
TI - Neural correlates of attention and arousal: insights from electrophysiology,
functional neuroimaging and psychopharmacology.
AB - Attention and arousal are multi-dimensional psychological processes, which
interact closely with one another. The neural substrates of attention, as well as
the interaction between arousal and attention, are discussed in this review.
After a brief discussion of psychological and neuropsychological theories of
attention, event-related potential correlates of attention are discussed.
Essentially, attention acts to modulate stimulus-induced electrical potentials
(N100/P100, P300, N400), rather than generating any unique potentials of its own.
Functional neuroimaging studies of attentional orienting, selective attention,
divided attention and sustained attention (and its inter-dependence on underlying
levels of arousal) are then reviewed. A distinction is drawn between the brain
areas which are crucially involved in the top-down modulation of attention (the
'sources' of attention) and those sensory-association areas whose activity is
modulated by attention (the 'sites' of attentional expression). Frontal and
parietal (usually right-lateralised) cortices and thalamus are most often
associated with the source of attentional modulation. Also, the use of functional
neuroimaging to test explicit hypotheses about psychological theories of
attention is emphasised. These experimental paradigms form the basis for a 'new
generation' of functional imaging studies which exploit the dynamic aspect of
imaging and demonstrate how it can be used as more than just a 'brain mapping'
device. Finally, a review of psychopharmacological studies in healthy human
volunteers outlines the contributions of the noradrenergic, cholinergic and
dopaminergic neurotransmitter systems to the neurochemical modulation of human
attention and arousal. While, noradrenergic and cholinergic systems are involved
in 'low-level' aspects of attention (e.g. attentional orienting), the
dopaminergic system is associated with more 'executive' aspects of attention such
as attentional set-shifting or working memory.
PMID- 9654385
TI - Basal ganglia organization in amphibians: evidence for a common pattern in
tetrapods.
AB - The results of recent studies investigating the connections and chemoarchitecture
of the basal forebrain of amphibians provide strong evidence that tetrapod
vertebrates share a common pattern of basal ganglia organization. This pattern
includes the existence of dorsal and ventral striatopallidal systems, reciprocal
connections between the striatopallidal complex and the diencephalic and
mesencephalic basal plate (striato-nigral and nigro-striatal projections), and
descending pathways from the striatopallidal system to the midbrain tectum and
reticular formation. The connectional similarities are parallelled by
similarities in the distribution of chemical markers of striatal and pallidal
structures such as dopamine, substance P and enkephalin. Moreover, studies of
development and expression of homeobox genes have given further support to the
notion that both amniotic and anamniotic tetrapods have a common pattern of basal
ganglia organization. A new nomenclature of basal forebrain structures in
amphibians is proposed which reflects our current understanding of basal ganglia
organization in this class of vertebrates.
PMID- 9654386
TI - Viral vectors, tools for gene transfer in the nervous system.
AB - Viral vectors are becoming increasingly important tools to investigate the
function of neural proteins and to explore the feasibility of gene therapy to
treat diseases of the nervous system. This gene transfer technology is based on
the use of a virus as a gene delivery vehicle. In contrast to functional analysis
of gene products in transgenic mouse, viral vectors can be applied to transfer
genes to somatic, post-mitotic cells of fully developed animals. To date, five
viral vector systems are available for gene transfer in the nervous system. These
include recombinant and defective herpes viral vectors, adenoviral vectors, adeno
associated viral vectors and lentiviral vectors. Of these vectors herpes and
adenoviral vectors are the most common in use. To date, one of the main hurdles
in applying these two vector systems is the focal immune response that occurs
following intraparenchymal infusion. Despite this limitation, herpes and
adenoviral vectors have been used successfully to modify the physiological
response to injury in several rodent models of neurodegeneration. The first
purpose of this review is to describe the principles of the generation of viral
vectors and to discuss the advantages and disadvantages of the viral vector
systems currently in use for gene transfer in the nervous system. Secondly, we
give an overview of the performance of these vectors following direct infusion in
the nervous system and review the results obtained with these vectors in animal
models of neurodegeneration and regeneration. The results of these initial
studies have provided a framework for future experiments based on gene transfer
strategies with viral vectors to study normal physiology and pathology of the
nervous system.
PMID- 9654387
TI - The role of art in human life.
PMID- 9654388
TI - Computers and medical education.
PMID- 9654389
TI - Platelet-activating factor antagonism: a new concept in the management of
regional myocardial ischemia-reperfusion injury.
AB - Reperfusion therapies for treatment of myocardial infarction successfully reduce
patient mortality; however, regional myocardial ischemia-reperfusion (RMIR)
causes its own expression of cardiovascular dysfunction, including myocardial
depression, hemodynamic instability, and dysrhythmias, which have increased
patient mortality within the first 24 h after starting reperfusion therapy.
Current evidence suggests that the release of oxygen-derived reactive substances
and subsequent inflammatory mediators during ischemia-reperfusion contribute
toward this injury. Platelet-activating factor (PAF), a mediator released during
RMIR, has been emphasized by many investigators as playing a central role in
causing RMIR injury. Similar cardiovascular dysfunctions that occur during RMIR,
including myocardial depression, hemodynamic instability, and dysrhythmias, occur
after administration of PAF and are ameliorated with PAF antagonists. Further,
PAF antagonists have been shown to be cardioprotective and improve survival when
administered before onset of reperfusion. A variety of phospholipid analogues,
naturally derived compounds, and synthetic compounds have been developed that
form the different classes of PAF antagonists, each with unique antagonizing
properties. Several of these compounds have successfully passed safety and
efficacy testing in humans; however, to date, no clinical trials have
investigated the protective effects of PAF antagonists against RMIR injury. A
current theory in the pathogenesis of RMIR injury considers the ischemic and
necrotic portion of the myocardium and regional dysfunction due to tissue
necrosis to be solely responsible for global cardiac dysfunction leading to
hemodynamic instability and death. Evidence now suggests, however, that the
global dysfunction is also due to the effect of inflammatory mediators such as
PAF, thromboxanes, leukotrienes, and endothelins that are released during RMIR
and are distributed throughout the heart on reperfusion. Antagonizing a central
inflammatory mediator such as PAF, as adjunct treatment with currently used
reperfusion therapies, improves cardiovascular function and survival in animals
and should be introduced into clinical trials to investigate if similar
protective effects can be provided in humans.
PMID- 9654390
TI - The role of electrolyte in lesion size using an irrigated radiofrequency
electrode.
AB - Multiple attempts have been made to eliminate atrial fibrillation by performing
the surgical maze procedure with radiofrequency energy. Currently, this is
limited because of the risk of atrial perforation and the lack of transmural
penetration. Saline irrigation has been investigated as a method of
radiofrequency cautery tip cooling to prevent rapid temperature and impedance
rises, which have been shown to lead to perforation or decreased radiofrequency
penetration after eschar formation. There are few data on the influence that
different types of electrolyte irrigation solutions have on lesion depth. Using a
novel hollow cautery pen, we infused either an electrolyte solution (0.9%, 3%,
14.6%, or 23.4% sodium chloride), a nonelectrolyte solution (1.5% glycine), or no
irrigation to produce 819 lesions on 14 left ventricles in swine using
radiofrequency energy (450+/-10 kHz) applied at two output settings (20 and 75
watts). The nonelectrolyte solution increased lesion depth compared with no
infusion at 20 watts but produced shallower lesion depths compared with
electrolyte solutions at 75 watts. Compared with the other electrolyte solutions,
the 0.9% sodium chloride solution produced the deepest lesions (3.34+/-0.06 mm)
at 75 watts (p < 0.001). As the concentration of electrolyte increased, lesion
depth decreased unless generator output increased. Formation of eschar and tissue
destruction was seen in the noninfusion and nonelectrolyte groups but not in the
electrolyte group. A conductive media coupled with radiofrequency energy allowed
for greater lesion depth than irrigated cooling with a nonelectrolyte solution or
no irrigation. There was an inverse relationship between electrolyte
concentration and lesion depth. We conclude that the concentration of electrolyte
irrigant is an important consideration when choosing a solution to improve
transmural penetration and decrease the risk of tissue destruction from
radiofrequency energy.
PMID- 9654391
TI - Depression of tumor necrosis factor-alpha, interleukin-6, and interleukin-10
production: a reaction to the initial systemic hyperactivation in septic shock.
AB - Sepsis remains a major cause of mortality in surgical intensive care units.
Patients who survive the initial shock phase but die weeks later from multiple
organ dysfunction still are a challenge to basic and clinical research. We
addressed whether fulminant sepsis results in rapid changes (24 h) in the
cellular capacity to produce cytokines in whole blood of septic patients on
further stimulation after the initial systemic inflammatory response. Interleukin
(IL)-6 plasma concentrations from 279 pg/mL to 5979 pg/mL confirmed the presence
of a systemic inflammatory response. Anti-inflammatory IL-10 concentrations up to
275 pg/mL were detected, but there was no biologically active tumor necrosis
factor-alpha (TNFalpha) detectable (by bioassay) at the time of investigation. On
stimulation with Escherichia coli ex vivo, pro-inflammatory TNFalpha (130 pg/mL),
IL-6 (4061 pg/mL), and anti-inflammatory IL-10 (711 pg/mL) production were
markedly depressed in all patients compared with controls (2339 pg/mL, 50,319
pg/mL, and 9654 pg/mL, respectively). Septic shock resulted in early depression
of the capacity for pro- and anti-inflammatory cytokine production. Monitoring of
this effect, including its relationship to outcome, may offer a target variable
for therapeutic efforts to maintain or restore adequate immune reactions to
improve survival.
PMID- 9654392
TI - Perfluorocarbons: future clinical possibilities.
AB - Perfluorocarbons are now being used as oxygen carriers in clinical settings.
Because these chemicals may have a role as a blood substitute, in organ
preservation, and in the management of respiratory failure, we have reviewed some
of the research leading to these applications.
PMID- 9654393
TI - Prevention of adhesion formation with intraperitoneal administration of tolmetin
and hyaluronic acid.
AB - Adhesion formation after peritoneal surgery is a major source of postoperative
complications and pain. Previous studies showed that intraperitoneal
administration of the nonsteroidal anti-inflammatory drug tolmetin reduced
adhesion formation after two types of peritoneal surgery. The effect of tolmetin
combined with hyaluronic acid (HA), a high-molecular-weight glucosaminoglycan
found in the extracellular matrix, on the formation of adhesions was examined. In
this study, the effect of tolmetin in HA on adhesion formation was evaluated in a
standardized rabbit model. The medicament was administered intraperitoneally at
the end of surgery. One week after surgery, a second laparotomy was performed and
the extent of adhesion formation was determined. A range of molecular weights
(7.5 x 10(5)-2 x 10(6) Da) and viscosities (1000-25,000 centapoise) of HA in
combination with tolmetin was effective in reducing adhesion formation. However,
low viscosity HA solutions in combination with tolmetin, 0.5-2.0 mg/mL, were most
efficacious in reducing adhesion formation. These data suggest that HA, in
combination with tolmetin, acts as an effective carrier to reduce adhesion
formation in the abdominal cavity after surgery.
PMID- 9654394
TI - Graft length affects outcome in fetal small bowel transplants.
AB - Multiple studies have demonstrated the ability of the fetal rat small intestine
to be transplanted successfully as a free graft, devoid of its mesentery. While
maintaining normal histologic architecture, portal circulation, and digestive and
absorptive properties, the initial myeloelectric activity is delayed. The purpose
of this study was to investigate how abnormal early motility affects functional
outcome and survival. Using a syngeneic model, fetal rat small intestine segments
were transplanted into adolescent rat recipients as free grafts into the omentum.
After a maturation period, viable segments measuring 1 or 2 cm were placed into
continuity with the native intestine after a standardized resection of either
jejunum-ileum, ileum-cecum, or cecum. Control animals had native intestinal
resection without graft interposition. Survival, daily weight gain, oral intake,
and fecal output were monitored. In this model, overall survival was improved
with the use of the shorter 1-cm graft segment compared with the 2-cm and more
distal interpositions. No animals survived with proximal graft placement after
jejunal-ileal resection. Nutrient use was improved in the transplant recipients
compared with nontransplant controls but did not differ between the two graft
lengths. These data suggest that outcome in this model is improved using shorter
fetal intestine graft lengths. The use of multiple segments in multistaged
procedures and early defunctionalization may improve results.
PMID- 9654395
TI - Mechanical characteristics of four allograft tendon-to-muscle anastomotic
techniques.
AB - Four methods of allograft tendon-to-muscle anastomosis were tested in single
cycle distraction to failure using 10 anastomosed ovine calcaneal tendon-biceps
brachii units. The tendon-muscle units were compared to intact ovine biceps
brachii muscle units. Methods of tendon-to-muscle anastomosis were derived from
modifications of existing muscle tendon repair and tenorrhaphy techniques. Load
to failure (N), stiffness (N/cm), distraction (cm), and modes of failure were
recorded. Of the four methods tested, the side-to-side technique demonstrated the
highest load to failure (152.1 N), the greatest stiffness (17.6 N/cm), the least
distraction (2.99 cm) before failure, and the least amount of muscle tissue
trauma at failure. Results indicate that, of the methods tested, the side-to-side
technique offers the greatest initial stability and should therefore allow
adequate revascularization and healing of the anastomosis site.
PMID- 9654396
TI - Experimental cardiomyopathy as a model of chronic heart failure.
AB - End-stage heart disease is a major health care issue and it represents one of the
most costly diseases. Several experimental heart failure models have been
developed; however, a single model is not widely accepted as representative of
clinical heart failure. The doxorubicin-induced cardiomyopathy model was used in
the current study to address two issues: 1) to define a standardized dose regimen
of intracoronary doxorubicin infusion; and 2) to establish a method of
determining the onset and time course of heart failure. Twenty dogs underwent
placement of an intracoronary catheter. A total dose of 1 mg/kg of intracoronary
doxorubicin was infused. Hemodynamics were obtained at weeks 0, 7, and 12.
Echocardiography was performed weekly. Right and left ventricular biopsy
specimens were examined at weeks 0 and 12. Survival after doxorubicin-induced
cardiomyopathy was 60% at week 12. The development of heart failure was
demonstrated by a significant decrease in left ventricular ejection fraction and
cardiac index and a significant increase in left ventricular end-diastolic
pressure and volume. The leukocyte count, hemoglobin, and hematocrit decreased
significantly. Histologic changes of both the right and left ventricular
myocardial biopsy specimens included myocellular hypertrophy, loss of
myofibrillar material, and vacuolization. Intracoronary doxorubicin reliably
produced an experimental model of accelerated heart failure that developed over
the course of 12 weeks. Echocardiographic monitoring allowed a close surveillance
of heart failure development. This model may be useful to evaluate the efficacy
of cardiomyoplasty, mechanical assist devices, transplantation, and reduction
ventriculoplasty.
PMID- 9654397
TI - Effects of low chronic ethanol exposure on prostaglandin E synthesis by
preimplantation mouse embryos.
AB - Embryo prostaglandin (PG) synthesis plays a role in the modulation of embryo
metabolism and viability, and in the beginning of the implantation. The effects
of ethanol consumption seem to be mediated at least in part by PGs. Increased PG
production of postimplantation embryos is associated with retardation and
abnormalities in the gestational period. The aim of this study was to find out
the effects of low chronic ethanol ingestion by mice, previous to pregnancy, on
the PGE released by in vitro and in vivo derived embryos. Immature females or
adult males were treated with 5% ethanol for 30 days. After fertilization and
mating, two-cell embryos, morulae and blastocysts were collected. The PGE
synthesis and release were measured by radioimmunoassay. PGE production by in
vitro derived two-cell embryos from ethanol-treated females was lower than in the
control group (P < 0.01). Also, PGE production was reduced when two-cell embryos
came from ethanol-treated males (P < 0.01). There were no differences in PGE
synthesis by in vitro derived morulae and blastocysts in these groups. Two-cell
embryos derived from mating produced lower quantities of PGE when they came from
ethanol-treated females mated with control males, as compared to the control
group. PGE release by in vivo derived blastocysts from ethanol-treated females
was reduced significantly, as compared to the control group (P < 0.01). We
conclude that a low concentration of ethanol administered chronically to immature
females reduces PGE synthesis and release by two-cell embryos from culture in
vitro, and by embryos of days 2 and 4 from in vivo development.
PMID- 9654398
TI - Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and
fibrinolytic activity in patients with coronary artery disease.
AB - Thirty patients with coronary artery disease (CAD) were administered garlic
(study group) while another 30 patients received the placebo (control group).
Various risk parameters were determined at 1.5 and 3 months of garlic
administration. Garlic, administered in a daily dose of 2 x 2 capsules (each
capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic),
reduced significantly total serum cholesterol and triglycerides, and increased
significantly HDL-cholesterol and fibrinolytic activity. There was no effect on
the fibrinogen and glucose levels. In vitro effects of the garlic oil on platelet
aggregation (PAg) and eicosanoid metabolism were examined; it inhibited PAg
induced by several platelet agonists, and also platelet thromboxane formation.
Two important paraffinic polysulphides - diallyl disulphide (DADS) and diallyl
trisulphide (DATS) - derived from garlic and are usual constituents of garlic
oil, showed antiplatelet activity, and also inhibited platelet thromboxane
formation. In this respect DATS was more potent than DADS. The nature of
inhibition of PAg by DATS was found to be reversible.
PMID- 9654399
TI - Inhibition of leukotriene synthesis by terfenadine in vitro.
AB - To determine the inhibitory mechanisms of terfenadine on the synthesis of
leukotriene C4 (LTC4), an important mediator in allergic diseases, we evaluated
the action of terfenadine on the IgE-dependent production of LTC4 in rat
basophilic leukaemia 2H3 cells. Rat IgE-loaded cells were stimulated with anti
IgE in the presence or absence of various concentrations of terfenadine and the
level of LTC4 released into the medium was measured by performing a specific
radio immunoassay. Terfenadine inhibited the synthesis of LTC4 to 67.2% at a
concentration of 5 microg/ml. LT synthesis was directly suppressed by inhibition
of 5-lipoxygenase (5-LO) through calcium ion-independent mechanisms, and was also
possibly suppressed by inhibition of cytosolic phospholipase A2 and 5-LO by
blocking the influx of intracellular calcium ion that was initiated by IgE
related stimulation.
PMID- 9654400
TI - Inhibition of EGF-dependent mitogenesis by prostaglandin E2 in Syrian hamster
embryo fibroblasts.
AB - Lipid metabolism can play an important role in the development and progression of
human cancers. We have used Syrian hamster embryo (SHE) fibroblasts as a model
system to study how lipid metabolites can alter cell proliferation and apoptosis.
For example, the linoleic acid metabolite 13(S)-HpODE enhances EGF-dependent
growth by inhibiting de-phosphorylation of the EGFR which leads to activation of
the MAP kinase pathway. In contrast, the arachidonic acid metabolite, PGE2,
inhibits EGF-dependent mitogenesis and the expression of the proto-oncogenes c
myc, c-jun, and jun-B. In this study, we have investigated the mechanism by which
PGE2 attenuates these responses by studying the EGF signaling cascade in SHE
cells. PGE2 pretreatment caused a concentration-dependent decrease in EGF
dependent phosphorylation of MAP kinase and a corresponding inhibition of EGF
stimulated MAP kinase activity. Pretreatment of the SHE cells with PGE2 had
little effect on the magnitude of EGF-dependent receptor auto-phosphorylation and
the phosphorylation of GAP suggesting a down-stream target. Treatment of cells
with forskolin and EGF causes similar inhibition of MAP kinase phosphorylation as
observed with PGE2 and EGF. Since PGE2 elevates cAMP in these cells, it may act
by altering cAMP accumulation. Raf-1 activity can be inhibited by a cAMP
dependent process. Raf-1 activity, measured by phosphorylation of Mek-1, was
attenuated by the addition of PGE2. To determine if inhibition of Raf-1 activity
causes inhibition of the MAP kinase pathway, cells were concomitantly incubated
with PGE2 and EGF. Inhibition of MAP kinase phosphorylation was observed. From
these data, we propose that in SHE cells PGE2 increases cAMP levels, which in
turn causes inhibition of Raf-1 activity. The MAP kinase pathway is thus
downregulated which decreases mitogenesis and proto-oncogene expression. This
study demonstrates that an arachidonic acid metabolite can modulate
phosphorylation and activity of key signal transduction proteins in a growth
factor mitogenic pathway.
PMID- 9654401
TI - In vitro activity of polyunsaturated fatty acids on Pseudomonas aeruginosa:
relationship to lipid peroxidation.
AB - Based on previous findings that gamma-linolenic acid (GLA) inhibits Escherichia
coli growth and provokes the induction of strains resistant to aminoglycosides,
19 Pseudomonas aeruginosa strains were exposed in vitro over time to GLA, to
arachidonic acid (AA) and to their combination in the presence or absence of
vitamin E. All acids were used at a 300 microg/ml concentration, whereas vitamin
E was added as an antioxidant. Lipid peroxidation was evaluated by the
thiobarbiturate assay measuring malonodialdehyde (MDA) production. It was found
that GLA or AA killed 5-10% of strains at 24 h of growth, whereas when applied in
combination their effect involved 100% of strains at 24 h and was limited to 68%
of strains in the presence of vitamin E (P< 0.01). MDA production was time
dependent and it was restrained by vitamin E (P < 0.01). Post acid exposure, 27%
to 37% of the survived strains became resistant to diverse antimicrobial agents
and mainly to ticarcillin, to ceftazidime and to amikacin; no strain developed
resistance in the presence of vitamin E. It is concluded that GLA and AA interact
bactericidally on P. aeruginosa isolates, inducing the development of strains
resistant to beta-lactams and to aminoglycosides; their action might be mediated
through their peroxides. Further research is necessary to establish the clinical
application of these in vitro findings.
PMID- 9654402
TI - Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor
alpha expression in activated murine lymphocytes.
AB - Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress
interleukin-2 (IL-2) secretion and impair T-lymphocyte proliferation. To
determine the mechanism of action, mice were fed diets containing either
safflower oil (control diet enriched in linoleic acid, 18:2n-6), EPA, DHA or
arachidonic acid (20:4n-6). Splenic lymphocytes were isolated and concanavalin A
induced kinetics of IL-2 and IL-2 receptor alpha mRNA expression were determined
by relative competitive-PCR. EPA and DHA did not affect IL-2 mRNA expression but
suppressed IL-2 receptor alpha mRNA levels. These data show, for the first time,
the selective effects of dietary EPA and DHA on T-lymphocyte gene expression.
PMID- 9654403
TI - Induction of apoptosis, p53 and heme oxygenase-1 by cytotoxic prostaglandin
delta12-PGJ2 in transformed endothelial cells.
AB - Delta12-prostaglandin (PG)J2, which has been reported to have potent growth
inhibitory activity in various tumor cells, induced apoptosis at 5 microg/ml
culture medium in transformed mouse endothelial (F2) cells. Immunoblot analysis
using anti-p53 or anti-WAF1 antibodies demonstrated that these two proteins had
increased following delta12-PGJ2 treatment in F2 cells. Western blotting analysis
using anti-heme oxygenase-1 (heat shock protein (HSP)32) antibody also revealed
that delta12-PGJ2 induced HSP32 formation in F2 cells. HSP32 was also induced by
heat shock treatment at 43 degrees C for 90 min. In contrast, HSP72 was not
induced by heat shock or by delta12-PGJ2 treatment. In agreement with these
findings, HSP32 immunofluorescence in the cytoplasm of F2 cells was intensified
by delta12-PGJ2 treatment. More intense HSP32 immunoreactivity was similarly
observed after heat shock treatment. These results suggest that delta12-PGJ2
caused the apoptotic cell death of F2 cells, which involved a certain process
required for p53 or HSP32 induction.
PMID- 9654404
TI - Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2
diacylglycerol fatty acid composition in thoracic aortas from diabetic rats.
AB - The effect of diabetes on the incorporation of long-chain n-3 fatty acids into
thoracic aorta smooth muscle phospholipids and 1,2-diacylglycerol, and on the
contractile response of aortic rings to angiotensin II, was examined in
streptozotocin-induced diabetic rats. In diabetic animals fed a diet containing
1% of fatty acids as n-3 fatty acids, smooth muscle membrane levels of 18:2n-6
were elevated in phosphatidylcholine, phosphatidylethanolamine and
phosphatidylinositol, whereas 20:4n-6 was depleted. The resultant decreased
ratios of 20:3/18:2 and 20:4/20:3 indicate inhibition of delta6- and delta5
desaturase activity in the diabetic state. A diet containing 5% of fatty acids as
n-3 fatty acids increased phospholipid levels of eicospentaenoic acid (EPA),
docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) several-fold, but with
a further reduction in 20:4n-6. Similarly, 1,2-diacylglycerol from rats fed the
high n-3 diet was enriched in EPA, DPA and DHA. When incubated with 10(-8) M
angiotensin II, the contractile response of intact aortic rings from diabetic
animals fed the high n-3 diet was only 60.8+/-9.3% that of controls fed the same
diet. However, contractile response was not significantly different from control
animals fed the low n-3 diet (55.6+/-7.9%). The results indicate that vascular
smooth muscle phospholipid n-6 and n-3 fatty acid metabolism is altered in
diabetes, resulting in changes to the fatty acid profile of 1,2-diacylglycerol.
Moreover, elevating membrane phospholipid and 1,2-diacylglycerol content of EPA,
DPA and DHA partially ameliorates the depressed response to angiotensin II seen
in the diabetic state.
PMID- 9654405
TI - Tumor metastasis inhibition with the prostacyclin analogue cicaprost depends on
discontinuous plasma peak levels.
AB - Stable prostacyclin analogues exert a strong inhibitory effect on lymphogenous as
well as haematogenous tumor metastasis in a series of tumor lines. The strong
inhibition of metastasis was achieved by repeated once-daily i.g. applications.
The mechanism of antimetastatic action is related to the expression of functional
IP-receptors (PGI-receptors). As cellular assay systems indicated that the IP
receptor mediated signalling is down-regulated upon continuous exposure to
prostacyclin or stable derivatives, it has been questioned whether a mode of drug
application with constant plasma drug levels may potentially result in a decrease
of the antimetastatic effect. We addressed this question using the stable
prostacyclin analogue cicaprost in a disease model by comparing i.g. applications
given once daily with a continuous administration of equivalent doses via
drinking water. Very similar to our previous investigations in the 13762NF MTLn3
rat mammary carcinoma model, cicaprost administered by i.g. application strongly
reduced lung and lymph node metastasis. In contrast, administration of equivalent
doses via drinking water leading to lower but constant steady-state plasma levels
failed to exert inhibitory effects. Plasma and urine levels of cicaprost were
measured with a sensitive radioimmunoassay on the last treatment day.
Pharmacokinetic evaluation demonstrated a similar bioavailability of cicaprost in
both groups. This result first demonstrates a treatment failure of a prostacyclin
derivative in a chronic disease model in association with a continuous drug
administration leading to constant plasma levels. A desensitization of receptor
signalling by constant plasma levels may be a possible mechanism for treatment
failure.
PMID- 9654406
TI - Radioimmunoassay of 8-iso-prostaglandin F2alpha: an index for oxidative injury
via free radical catalysed lipid peroxidation.
AB - 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a major F2-isoprostane, is
biosynthesized in vivo through nonenzymatic free radical-catalysed peroxidation
of arachidonic acid. The levels of F2-isoprostanes both free in the circulation
and esterified to the tissue phospholipids increase intensely in animal models of
oxidant injury. This study presents the development and validation of a
radioimmunoassay of 8-iso-PGF2alpha for the measurement of this substance in the
body fluids. Furthermore, its application in normal human volunteers, a
pharmacokinetic study performed in rabbits with 8-iso-PGF2alpha, and hepatic
lipid peroxidation in rats is reported. An antibody was raised in rabbits by
immunization with 8-iso-PGF2alpha coupled to BSA at the carboxylic acid by 1,1'
Carbonyldiimmidazole method. The cross-reactivity of the antibody with 8-iso-15
keto-13,14-dihydro-PGF2alpha, 8-iso-PGF2beta, PGF2alpha, 15-keto-PGF2alpha, 15
keto-13,14-dihydro-PGF2alpha,TXB2, 11beta-PGF2alpha, 9beta-PGF2alpha and 8-iso
PGF3alpha was 1.7, 9.8, 1.1, 0.01, 0.01, 0.1, 0.03, 1.8 and 0.6%, respectively.
The intraassay precision was 14.5% (CV) at the level of 64 pg/0.1 ml and 12.2%
with 512 pg/0.1 ml in the human plasma. Similarly, intra-assay accuracy was 95.6%
and 101% for the low and the high standard, respectively. The detection limit was
about 23 pmol/l. The appearance and disappearance of 8-iso-PGF2alpha in the blood
and urine following intravenous administration of 8-iso-PGF2alpha in the rabbit
was rapid. Free 8-iso-PGF2alpha levels in plasma and urine from normal human
volunteers are evaluated and found to correlate with the obtained values by gas
chromatography-mass spectrometry methods from other studies. The levels of free 8
iso-PGF2alpha in the plasma and urine increased 7- and 102-fold, respectively,
after CCl4 administration to rats. Thus, this 8-iso PGF2alpha radioimmunoassay
method is relevant to apply in the oxidative injury studies as an index of in
vivo lipid peroxidation through free radical catalysis mechanism.
PMID- 9654407
TI - Effect of gammalinolenic acid, dihomogammalinolenic acid, ascorbyl-6
gammalinolenic acid, and ascorbyl-6-dihomo gammalinolenic acid on histamine- and
methacholine-induced contraction of the isolated guinea pig tracheal chain.
AB - The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid
(DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect
of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic
acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA)
were investigated and the role of the epithelial cells was determined. Salbutamol
was used as control. The isolated tracheas of six to eight guinea pigs were used
in each experiment and suspended in organ baths filled with Krebs-Henseleit
solution and aerated with 95% O2 and 5% CO2. The relaxant effects produced for
histamine-contracted preparations were as follows: AA=71.2+/-0.2%, GLA=55.2+/
4.2%, DGLA=69.8+/-3.9%, ascorbyl-6-GLA =26.2+/-5.1% and ascorbyl-6-DGLA=54.5+/
2.4%. For methacholine-contracted preparations: AA=46.6+/-3.2%, GLA=55.0+/-9.5%,
DGLA=61.8+/-2.7%, ascorbyl-6-GLA=40.0+/-8.0% and ascorbyl-6-DGLA=88.0+/-15.3%.
Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect
compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced
contraction, which showed a significant increased relaxant effect. The removal of
the epithelium showed decreased relaxant effects for the drugs except AA, which
showed increased values after methacholine contraction. Histamine-contracted
preparations showed varied results. Ascorbyl-6-GLA showed an increased relaxant
effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6
DGLA showed decreased relaxant effects. In conclusion, it is clear that the
contractant and the availability of epithelial cells could ultimately determine
the results, though the mechanism remains very complex. The benefit of added
ascorbate is still unclear and warrants more investigation.
PMID- 9654408
TI - Wanted: optimal data regarding surgery for retinal detachment.
PMID- 9654409
TI - A tribute to Robert Machemer, MD, on the occasion of his retirement.
PMID- 9654410
TI - Histoplasmosis-like choroiditis in a nonendemic area: the northwest United
States.
AB - PURPOSE: Histoplasmosis is not endemic in the U.S. northwest, but a type of
multifocal choroiditis resembling ocular histoplasmosis occurs there. This study
was designed to find a group of affected patients and study their clinical
characteristics and immunologic responses to Histoplasma antigens. METHOD: Ten
patients were found in the authors' files whose geographic histories made it
unlikely that they had ever been exposed to Histoplasma capsulatum and yet they
had features of ocular histoplasmosis. They were recalled for examination and
testing by lymphocyte-stimulation assay for previous exposure to histoplasmosis.
RESULTS: The clinical features of these patients resembled those of patients with
ocular histoplasmosis, but their histories and the results of the assay did not
support H. capsulatum as the cause of the ocular disease. CONCLUSION: This study
confirmed that there is a type of choroiditis that resembles ocular
histoplasmosis but is due to another agent or agents.
PMID- 9654411
TI - Management of glass intraocular foreign bodies.
AB - PURPOSE: To describe the results of management of glass intraocular foreign
bodies (IOFBs). METHODS: A total of 51 eyes of 43 patients that sustained
penetrating injury with glass IOFB were studied retrospectively. A total of 23.5%
had IOFB only in the anterior segment; the rest had IOFB in the posterior segment
alone or in both the anterior and posterior segments. Six eyes were followed
conservatively despite IOFB in a functional eye. Removal of IOFB was combined
with repair of retinal detachment (where present) using internal tamponade with
gas or silicone oil or buckle. RESULTS: After a mean follow-up of 16.8 months,
66.7% of eyes recovered better than 6/60 (20/200) vision and 75.6% had attached
retina. On univariate analysis, scleral entry wound, posterior segment IOFB,
larger size of IOFB, and retinal damage were found to be associated with poor
anatomic outcome. Lower presenting visual acuity, hyphema, retinal damage,
subretinal hemorrhage, detached retina, and larger IOFB were associated with a
poor functional result. Multivariate analysis identified retinal damage caused by
the foreign body as the only factor significantly associated with poor anatomic
as well as functional outcome. CONCLUSIONS: Glass IOFBs are caused in a majority
of cases by blast injury. Bilaterality is not uncommon. Presence of retinal
damage is predictive of poor functional and anatomic results. Overall results are
modest with modern vitreoretinal surgical techniques.
PMID- 9654412
TI - Vitrectomy and silicone oil injection in pediatric patients.
AB - OBJECTIVE: To determine the functional and anatomic results of vitrectomy with
silicone oil injection in complicated retinal detachments in children. DESIGN: A
retrospective review of all records of children aged 15 years or younger who
underwent vitrectomy with silicone oil injection between 1985 and 1994 in the
Goldschleger eye institute. RESULTS: Twenty-eight eyes of 27 patients were
included in the series, with a mean follow-up time of 24 months. The underlying
pathologies included penetrating injury (11 eyes), high myopia (8 eyes),
choroidal coloboma (2 eyes), retinopathy of prematurity (2 eyes), and various
other pathologies (5 eyes). At the end of the follow-up, complete or partial
anatomic success was obtained in 9 eyes (32%) and 3 eyes (10%), respectively. The
final visual acuity was 20/400 or better in 5 eyes (18%) and hand motions or less
in 19 eyes (68%). The visual acuity could not be determined in 3 eyes due to the
age of the patients, and in 1 eye due to mental retardation. The worst results
occurred in the perforating injury group. The usual complications associated with
silicone oil occurred frequently. CONCLUSIONS: Satisfactory anatomic and
functional results were obtained in a minority of the eyes included in our
series. The grave prognosis was determined by the devastating nature of the
external injury in the trauma cases and the severe vitreoretinal pathology in the
other eyes.
PMID- 9654413
TI - Silicone oil removal combined with macular pucker dissection: a retrospective
review of 14 cases.
AB - PURPOSE: Silicone oil must be removed from the eye to avoid late complications
after the surgical management of proliferative vitreoretinopathy (PVR). Macular
pucker, frequently observed after retinal detachment surgery, is responsible for
visual impairment. The safety of a procedure combining epimacular membrane
peeling and silicone oil removal was retrospectively evaluated. METHODS: Fourteen
eyes that had previously undergone vitrectomy and silicone oil tamponade for
rhegmatogenous retinal detachment with severe PVR, penetrating or blunt trauma,
and intraocular foreign bodies were included. Silicone oil tamponade was
maintained for a mean period of 30 weeks (range, 12-108 weeks). The removal of
silicone oil was combined with the peeling of an epimacular membrane. RESULTS:
Mean follow-up after silicone oil removal was 86 weeks (range, 13-234 weeks). The
final retinal reattachment rate was 78%. Macular pucker recurred in one eye after
a 24-month period. Best-corrected visual acuity improved two lines or more in
eight eyes (57%) and reached 20/200 or better in eight eyes (57%) at last follow
up. CONCLUSION: Macular pucker dissection and silicone oil removal can be safely
combined. This single procedure can obviate the need for further surgery in eyes
that have already undergone multiple operations and allows good visual recovery.
PMID- 9654414
TI - Long-term follow-up of perfluorocarbon liquid in the anterior chamber.
AB - BACKGROUND: Perfluorocarbon liquids are used as a vitreous substitute in the
operative management of several ophthalmologic conditions. We examined the
effects of residual perfluorocarbon droplets in the anterior chamber in patients
after retinal detachment surgery. METHODS: The study group consisted of seven
patients (seven eyes) aged 28-74 years in whom droplets of perfluorocarbon
appeared in the anterior chamber subsequent to retinal detachment surgery
involving scleral buckling, perfluorodecalin injection, and perfluorocarbon
liquid-silicone oil exchange. Mean follow-up was 9.4 months. RESULTS: From 1 -15
droplets of perfluorocarbon liquid were found in the anterior chamber. There were
no corneal complications or inflammatory reactions or blood vessel invasion into
the corneal stroma. Some of the droplets appeared to be encapsulated in a
membrane-like material. Perfluorocarbon liquid and silicone oil had to be removed
in three patients at 20, 12, and 4 months postoperatively because of an increase
in intraocular pressure due to blockage of the inferior iridectomy by a droplet
of perfluorocarbon, emulsification of the silicone oil, or residual
perfluorocarbon liquid on the retina (one patient each). Increased intraocular
pressure in a fourth patient was successfully treated pharmacologically.
CONCLUSION: Based on our experience, residual perfluorocarbon liquid droplets in
the anterior chamber are well tolerated and do not induce corneal damage or
ocular inflammation. These patients should be closely followed, however, and the
liquid removed if complications develop.
PMID- 9654415
TI - Diffuse anterior retinoblastoma.
AB - PURPOSE: The authors describe the clinicopathologic features of an anterior
variant of diffuse retinoblastoma. METHODS: The clinical history of a child with
an anterior chamber infiltrate and cells in the anterior vitreous was reviewed.
An anterior chamber aspirate was processed by a Millipore filter technique. The
eye was enucleated and routinely processed for light and transmission electron
microscopic examination. RESULTS: An 8-year-old girl was treated for anterior
uveitis in her right eye that failed to resolve. Examination of an anterior
chamber aspirate showed cells suggestive of retinoblastoma. The eye was
enucleated, and the enucleation specimen showed retinoblastoma confined to the
iris, ciliary body, and anterior vitreous with one microscopic focus of tumor in
the peripheral retina. CONCLUSION: This variant of diffuse retinoblastoma
involved only anterior ocular structures with minimal involvement of the retina.
PMID- 9654416
TI - Photocoagulation of well-defined choroidal neovascularization in age-related
macular degeneration: clinicopathologic correlation.
AB - PURPOSE: To present the clinicopathologic features of the eyes of a patient with
age-related macular degeneration (ARMD): the right eye was treated for well
defined extrafoveal choroidal neovascularization (CNV), and the left eye had an
untreated disciform scar. METHODS: The patient was studied ophthalmoscopically
and by fluorescein angiography at the time of presentation and on follow-up
examinations up to 54 days after laser treatment, when he died. The posterior
portions of both eyes (obtained postmortem), including the macula and optic nerve
head, were sectioned serially for light microscopy. Tissue sections from both
eyes were removed from glass slides and studied by transmission electron
microscopy. RESULTS: Histopathologic study of the right eye disclosed a thin
layer of basal laminar deposit throughout the posterior pole. Two defects in
Bruch's membrane without CNV were present within the area of laser
photocoagulation located superior to the fovea. No CNV was present in the scar.
Eleven areas of early CNV were present in the posterior pole. Histopathologic
study of the left eye showed a prominent basal laminar deposit throughout the
posterior pole. A 2.6 x 2.7 mm disciform scar was present that was located mostly
in the subretinal space. Four sources of CNV were present. CONCLUSIONS: The
clinicopathologic features of a treated eye with well-defined extrafoveal CNV,
and the fellow eye with a disciform scar, both associated with ARMD, are
presented. Although laser treatment obliterated a choroidal neovascular membrane,
11 additional areas of early, subclinical CNV were present.
PMID- 9654417
TI - Three-dimensional ophthalmic contact B-scan ultrasonography of the posterior
segment.
AB - PURPOSE: A system to produce three-dimensional computer reconstructions of
ophthalmic contact B-scan ultrasound was developed and investigated. METHODS:
Investigators used ocular phantoms to measure the accuracy and reproducibility of
linear, area, and volume measurements. RESULTS: In vitro calibration tests of
linear and area measurements demonstrate accurate and reproducible findings
throughout the imaged space. Phantom volume tests also show reasonable accuracy
and reproducibility. CONCLUSIONS: Three-dimensional ultrasonography is effective
in measuring length, area, and volume in an experimental model. The in vitro
accuracy and reproducibility of measurements warrants further investigation into
the clinical utility of this method in posterior segment tumors and other
posterior segment pathology.
PMID- 9654418
TI - Inhibition of postvitrectomy fibrin using troxerutin.
AB - PURPOSE: To evaluate the efficacy of intraocular infusion of troxerutin in the
inhibition of fibrin formation after vitrectomy in a rabbit model. METHODS:
Lensectomies and vitrectomies were performed in a masked fashion on seven eyes
treated with a 10-mM infusion of troxerutin and on seven control eyes that
received only a balanced salt solution infusion. Masked grading of intraocular
fibrin formation and intravitreal hemorrhage was performed for 1 week. RESULTS:
On postoperative days 1 and 2, the control group exhibited a greater mean fibrin
index (MFI) percentage than the troxerutin-treated group (day 1, 27.7% versus
19.5% MFI; day 2, 14.5% versus 6.1% MFI, respectively). On postoperative day 3,
both groups showed an MFI of 1.8%. On postoperative days 5 and 7, both groups
showed only minimal presence of fibrin. Neither of the two groups had an
increased rate of intraocular hemorrhage. CONCLUSIONS: Infusion of 10 mM
troxerutin resulted in a relative decrease in the amount of fibrin produced
without an increased risk of intraocular hemorrhage in treated eyes compared with
controls, but the difference was not statistically significant. Further studies
may be warranted to evaluate the optimal dose of troxerutin alone or a possible
role for its use in conjunction with other drugs employing a different mechanism
of action in the prevention of fibrin formation.
PMID- 9654419
TI - Disparity between fundus camera and scanning laser ophthalmoscope indocyanine
green imaging of retinal pigment epithelium detachments.
AB - PURPOSE: Indocyanine green (ICG) angiograms of each of five patients with retinal
pigment epithelium (RPE) detachments were made using first a Topcon fundus camera
and then a Heidelberg scanning laser ophthalmoscope (SLO); for each patient, both
types of angiograms were obtained on the same day. In each case, the serous fluid
appeared bright throughout the fundus camera studies and dark throughout the SLO
studies. This study sought to explain the disparity in the appearance of the
lesions in the two kinds of images and to determine whether there was dye in the
serous fluid. METHODS: Simple model eyes were constructed to demonstrate the
effects of Mie light scatter and integrating sphere behavior of the sclera on ICG
image formation by the fundus camera and SLO optics. Analysis was made of both
the clinical angiograms and model eye images to structure an explanation for the
disparate RPE detachment angiographic images. RESULTS: Indocyanine green
fluorescent light from choroidal vessels adjacent to the lesions and scattered by
the turbid serous fluid accounted for the lesion brightness seen in the fundus
camera images. The models confirmed that SLOs suppress scattered light.
CONCLUSIONS: The apparent fluorescence of serous fluid beneath RPE detachments in
fundus camera early-phase ICG angiogram images is not attributable to the
presence of dye; rather, it appears to be attributable to serous fluid light
scatter of fluorescent light arising from adjacent fluorescent structures. This
light scatter is a consequence of the fundus camera illumination and recording
optics and is not present in SLO-generated images. The necessity of understanding
such phenomena as absorption, diffraction, polarization, and scatter of light and
routinely applying them to ICG angiogram interpretation is underscored when it is
shown that they offer simple explanations for unusual or unexpected angiographic
results, as in the case of the patients with RPE detachment discussed here.
PMID- 9654420
TI - Diagnostic and therapeutic challenges.
PMID- 9654421
TI - Recurrent cryptococcal choroiditis in a renal transplant patient:
clinicopathologic study.
PMID- 9654422
TI - Leber's neuroretinitis in a patient with serologic evidence of Bartonella
elizabethae.
PMID- 9654423
TI - Management of suspected endophthalmitis in vitrectomized, gas-filled eyes.
PMID- 9654424
TI - Bilateral endogenous Candida endophthalmitis.
PMID- 9654425
TI - Sulfur hexafluoride does not escape from plastic syringes capped with fine
needles.
PMID- 9654426
TI - Autogenous fascia lata leg grafts for exposed scleral buckles.
PMID- 9654427
TI - Lung carcinoma metastatic to the vitreous cavity.
PMID- 9654428
TI - Definition of macular hole surgery end points: elevated/open, flat/open,
flat/closed.
PMID- 9654429
TI - Severe ocular trauma managed with primary pars plana vitrectomy and silicone oil.
PMID- 9654430
TI - Verb retrieval and sentence production in aphasia.
AB - This paper presents a subject with a selective verb retrieval deficit. Nouns were
produced more successfully than verbs in spontaneous speech, picture naming and
when naming to definition. The word class effect was not observed in
comprehension tasks, reading aloud or writing. This indicated that it was due to
a specific problem in accessing verbs' phonological representations from
semantics. The second part of the paper explores the implications of the verb
deficit for sentence production. Analyses of narrative speech revealed a
typically agrammatic profile, with minimal verb argument structure and few
function words and inflections. Two investigations suggested that the sentence
deficit was at least partly contingent upon the verb deficit. In the first, the
subject was asked to produce a sentence with the aid of a provided noun or verb.
The noun cues were not effective in eliciting sentences, whereas verb cues were.
The second investigation explored the effects of therapy aiming to improve verb
retrieval. This therapy resulted in better verb retrieval and improved sentence
production with those verbs. These findings suggest that an inability to access
verbs' phonological representations can severely impair sentence formulation.
Implications for models of sentence production are considered.
PMID- 9654431
TI - Sentence production by aphasic patients in a constrained task.
AB - Sixty aphasic patients and 55 normal control subjects were tested on a sentence
production protocol that required subjects to produce specific sentence types
from semantic representations. Normal subjects produced the expected targets with
great reliability. Analysis of the patients' performance indicated that patients
had difficulty producing both grammatical forms and thematic roles. Patients had
more trouble producing grammatical elements than content words, and showed
differential difficulty on sentence types that had more grammatical elements and
in which the order of thematic roles was non-canonical. The results provide
evidence regarding the processing load imposed by different components of the
sentence production process.
PMID- 9654432
TI - Constraints on sentence priming in the cerebral hemispheres: effects of
intervening words in sentences and lists.
AB - This study explored the role of syntactic organization on semantic facilitation
for target words presented to the right (R) and left (L) visual fields (VFs).
Sentence and unstructured list primes were contrasted and, in each condition, the
effect of intervening unrelated words on the durability of priming within each
VF/hemisphere was investigated. Each prime contained a critical word which
occurred Near (one intervening word) or Far (six intervening words) from the
target word and was semantically related to it or a neutral control. It was
hypothesized that, for word lists, facilitation for RVF target words would
decrease with increasing distance between the critical and target words. For
sentences no decrease in facilitation was expected for RVF targets. However, for
LVF targets, facilitation was expected to decrease with distance both for
sentences and lists with no greater priming for sentences than for lists. The
results supported these hypotheses. Priming effects that spanned several
intervening items were found only when the primes were well-structured, normal
sentences and the target words were presented to the RVF. These results suggest
that while word-level priming processes are available to both hemispheres, the
left hemisphere makes greater use of message-level syntactic and semantic
mechanisms for sentence comprehension.
PMID- 9654433
TI - First-language acquisition in adolescence: evidence for a critical period for
verbal language development.
AB - It has been hypothesized that there is a critical period for first-language
acquisition that extends into late childhood and possibly until puberty. The
hypothesis is difficult to test directly because cases of linguistic deprivation
during childhood are fortunately rare. We present here the case of E.M., a young
man who has been profoundly deaf since birth and grew up in a rural area where he
received no formal education and had no contact with the deaf community. At the
age of 15, E.M. was fitted with hearing aids that corrected his hearing loss to
35 dB, and he began to learn verbal Spanish. We describe his language development
over the 4-year period since his acquisition of hearing aids and conclude that
the demonstrates severe deficits in verbal comprehension and production that
support the critical period hypothesis.
PMID- 9654434
TI - Effects of unilateral spatial neglect on spatial agraphia of kana and kanji
letters.
AB - Left unilateral spatial neglect (USN) and spatial agraphia are both caused by
right hemisphere damage. However, effects of USN on spatial agraphia have not
been fully investigated. This study examined performances of patients with or
without neglect and normals on single letter writing, using Japanese unique
writing systems, kana (phonogram) and kanji (ideogram). Our patients exhibited
agraphia of kanji, but not of kana. However, accuracy of writing was not
associated to neglect severity, and errors for writing to dictation occurred
either on the left or right side of kanji. Right frontal damage seemed to be
related to the genesis of duplication or omission errors of repeated elements.
Effect of USN was limited to spatial arrangement of letters and copying
performance.
PMID- 9654435
TI - Consonant and vowel production of right hemisphere patients.
AB - Recent reports of subclinical phonetic deficits in posterior and most
particularly in Wernicke's aphasics have challenged the traditional dichotomy
which characterized speech deficits in aphasia as anterior/phonetic and
posterior/phonological. It is unclear whether the basis of the phonetic deficit
in posterior aphasics reflects the fact that the speech production system extends
to more posterior regions of the left hemisphere than previously thought or
alternatively is the result of generalized brain damage effects. The present
study explores the latter possibility by investigating the patterns of speech
production in right hemisphere brain-damaged, non-aphasic patients with anterior
and posterior lesions. Acoustic analyses conducted on a range of consonant and
vowel parameters showed differences between the speech patterns of both anterior
and posterior right hemisphere patients and that of Wernicke's aphasics. These
findings suggest that the subclinical deficit of Wernicke's aphasics can not
simply be ascribed to a generalized brain-damage effect and raise the possibility
that the right hemisphere also plays some role, if only a minor one, in the
phonetic implementation of speech.
PMID- 9654437
TI - Evidence for a global categorical representation of humans by young infants.
AB - The representation of pictorial exemplars of humans by young infants was
examined. Experiments 1B and 2 demonstrated an asymmetry with respect to the
exclusivity of the categorical representations formed by 3- and 4-month-olds for
humans and non-human animal species. The categorical representation for humans
included novel humans, horses, cats, and fish, but excluded cars; the categorical
representation for horses included novel horses, but excluded humans, fish, and
cars. Experiment 2 also showed that the categorical representation for humans
included exemplar information, whereas the categorical representation for non
human animal species was based on summary information. The asymmetry in
categorization of human versus non-human animal species did not extend to the
presumed more basic process of discrimination of individual humans versus non
human animals (Experiment 3). The findings suggest that a broad categorical
representation of humans may be a cognitive reference point (or region) for young
infants.
PMID- 9654438
TI - Age changes in the missing-letter effect reflect the reader's growing ability to
extract the structure from text.
AB - Readers searching for a target letter in text are more likely to miss it in
frequent function words than in less frequent content words, and the magnitude of
this effect increases with age. While this increase has been taken to indicate
that proficient readers process familiar words in terms of larger orthographic
units, we propose that it reflects the reader's growing ability to extract the
structure of text, resulting in a reduced emphasis on function than on content
words. Indeed, comparing 2nd graders (7 to 7 1/2 years) and college students
(Experiment 1) this increase was found even when function and content words were
equated for frequency. Scrambling words within a sentence (Experiment 2) improved
letter detection in function compared to content words among 7th graders (12 to
13 years) and college students, but not among 3rd graders (8 to 9 years).
Although letter detection was also affected by word frequency, the age
differences noted above are possibly due not to the increasing familiarity of
words, but rather to the growing sensitivity to their structural role in text.
PMID- 9654439
TI - Implicit sequence learning in children.
AB - The main purpose of the present study was to examine whether implicit learning
abilities, assessed by means of a serial reaction time task, are present to the
same extent in 6- and 10-year-old children as in adults. We also wondered whether
the knowledge acquired after one learning session is retained after a 1-week
delay. And finally, we studied the explicit knowledge developed by the children
in this task. Our results show no age-related difference in the serial reaction
time performance, which is consistent with the idea that implicit learning
abilities may be efficient early in development.
PMID- 9654442
TI - Are there non-trivial dynamic cross-correlations in proteins?
AB - The analysis of internal motion in ensembles of flexible molecules in coordinate
space requires the removal of overall motion by a least-squares fitting procedure
of the Cartesian coordinates. It has been demonstrated that the choice of the
atom set used for fitting influences the picture of the internal motion of BPTI.
We have performed essential dynamics analyses of a 1 ns molecular dynamics
trajectory of the single-stranded DNA-binding protein from the Pf3 phage using
either all alpha-carbon atoms or the least mobile ones for fitting the trajectory
prior to the analysis. We found that covariances of atoms separated by long
distances were significantly reduced in the latter case; the overall overlap of
essential spaces was still high. In the second part we present a method that does
not introduce and bias caused by overall motion: principal component analysis in
distance space. Non-trivial dynamic cross-correlations were preserved in distance
space, which answers the question posed in the title in the affirmative. However,
cross-correlations were throughout smaller than those detected by standard
essential dynamics analyses.
PMID- 9654443
TI - Crystal structure of a dominant B-cell epitope from the preS2 region of hepatitis
B virus in the form of an inserted peptide segment in maltodextrin-binding
protein.
AB - We report here the crystal structure of MalE-B363, a recombinant construction of
maltodextrin-binding protein bearing a dominant B-cell epitope sequence from the
preS2 region of the hepatitis B surface antigen. The inserted peptide sequence,
which replaces the seven carboxy-terminal residues of maltodextrin-binding
protein, carries the 14 amino acid residue epitope contained between residues 132
and 145 from the preS2 region. The epitope sequence is flanked on either side by
additional residues that result from the genetically engineered insertion,
bringing the total length of the foreign peptide to 26 amino acid residues. The
hybrid protein has been previously shown to be recognised by monoclonal
antibodies elicited by the native viral antigen. Three independent molecules of
MalE-B363 are present in the asymmetric unit of the crystal. All 14 epitope
residues could be traced for one molecule, ten epitope residues had significant
electron density for the second, but no density was visible for the epitope of
the third. The conformation of the amino-terminal segment of the epitope from
Gln132(e) to Gly138(e) is similar in the two molecules of MalE-B363 for which the
foreign peptide could be traced. Moreover, the conformation of a smaller segment,
comprising residues Asp133(e) to Arg137(e), is similar to that present in the
previously determined crystal structure of MalE-B133, another insertion/deletion
mutant of maltodextrin-binding protein bearing the preS2 epitope. The presence of
a common structural motif for the same sequence in disparate molecular
environments suggests that this conformation might be present also in the native
viral antigen. This could provide a structural basis to explain the cross
reactivity of anti-preS2 monoclonal antibodies with these hybrid proteins.
PMID- 9654444
TI - The mitochondrial processing peptidase behaves as a zinc-metallopeptidase.
AB - The yeast mitochondrial processing peptidase (MPP) and its subunits were purified
in Escherichia coli under conditions for which the enzyme retains most of its
processing activity in the absence of externally added divalent cation. The
holoenzyme exhibited a Km value of 1.35 microM and a Vmax value of 0.25
microM/min and was inhibited by metal chelators in a time-dependent manner.
Measurement of the metal content showed that both, MPP and beta-MPP, contained
0.86 and 1.05 atoms of Zn2+ per molecule, respectively. An enzymatically inactive
MPP mutant carrying a mutation of the first histidine of the putative metal-ion
binding HXXEH motif in beta-MPP retained less than 0.2 atom of Zn2+ per molecule.
A metal-free enzyme (apoenzyme) was prepared from the holoenzyme and shown to be
devoid of any processing activity. Incubation of the apoenzyme with 50 nM and 500
nM Zn2+ restored 50% and 80% of the processing activity, respectively. However,
no reactivation occurred at concentrations of Zn2+ higher than 1 microM. Addition
of 500 nM Mn2+ or higher concentrations (up to 50 microM) reactivated only 50% of
the processing activity. The holoenzyme was competitively inhibited by molar
excess of Zn2+ (Ki of 3.1 microM) but not by molar excess of Mn2+. Taken
together, our data suggest that the authentic MPP is a Zn2+ rather than a Mn2+
metallopeptidase.
PMID- 9654445
TI - Pausing and termination by bacteriophage T7 RNA polymerase.
AB - Two types of sites are known to cause pausing and/or termination by bacteriophage
T7 RNA polymerase (RNAP). Termination at class I sites (typified by the signal
found in the late region of T7 DNA, TPhi) involves the formation of a stable stem
loop structure in the nascent RNA ahead of the point of termination, and results
in termination near runs of U. Class II sites, typified by a signal first
identified in the cloned human preproparathyroid hormone (PTH) gene, generate no
evident structure in the RNA but contain a conserved sequence ahead of the point
of termination, and also contain runs of U. Termination at class I and class II
sites may involve non-equivalent mechanisms, as mutants of T7 RNA polymerase have
been identified that fail to recognize class II sites yet continue to recognize
class I sites. In this work, we have analyzed pausing and termination at several
class II sites, and variants of them. We conclude that the 7 bp sequence ATCTGTT
(5' to 3' in the non-template strand) causes transcribing T7 or T3 RNA polymerase
to pause. Termination 6 to 8 bp past this sequence is favored by the presence of
runs of U, perhaps because they destabilize an RNA:DNA hybrid. The effects of T7
lysozyme on pausing and termination are consistent with the idea that termination
involves a reversion of the polymerase from the elongation to the initiation
conformation, and that lysozyme inhibits the return to the elongation
conformation. A kinetic model of pausing and termination is presented that
provides a consistent interpretation of our results.
PMID- 9654446
TI - Possible roles of nucleocapsid protein of MoMuLV in the specificity of proviral
DNA synthesis and in the genetic variability of the virus.
AB - Retroviral nucleocapsid (NC) protein, in addition to its structural roles in the
virion core, is involved in the early and late phases of the viral replication
cycle. To further characterise the role of NC protein of MoMuLV (NCp10) in the
replication of the viral genome, the influence of NCp10 on self-primed versus
primer-specific reverse transcription has been analysed in vitro. The results
show that NCp10 can enhance the specificity of proviral DNA synthesis by
inhibiting self-primed cDNA synthesis while promoting primer-specific DNA
synthesis within active NCp10-RNA nucleoprotein complexes. Retroviruses are known
to show a high degree of variability and this prompted us to examine the possible
implication of NCp10 in the genetic variability of MoMuLV. The ability of reverse
transcriptase (RT) to extend different mutated primers using an RNA or a DNA
template has been investigated in the presence or in the absence of NCp10. NCp10
was found to have different effects on RT depending on the nature of the
template: an enhancement at the elongation level of mutated primers using RNA as
template versus a slight inhibition using DNA as template. These observations
suggest that NCp10 could be implicated in the genetic variability of MoMuLV by
allowing nucleotide misincorporation principally during minus strand DNA
synthesis.
PMID- 9654447
TI - A minisatellite "core" element constitutes a novel, chromatin-specific activator
of mts1 gene transcription.
AB - Expression of the mts1 gene is often associated with malignant transformation of
tumor cells. Transcription of the gene is controlled by a number of positive and
negative regulatory elements, all of them being localized in the first intron
(+38 to +1215) of the mts1 gene. Through analysis of the distribution of DNase I
hypersensitive sites in the first intron of the gene we revealed a structurally
conserved region that consisted of a non-canonical NFkB binding site and a
minisatellite "core" element. Deletion of the minisatellite core DNA in the
context of the first intron had no effect on its regulatory capacity when assayed
in transient transfections, while a fivefold decrease was observed in a pool of
stably transfected cells. The minisatellite core sequence CTGGGCAGGCAG is
involved in DNA-protein interactions in vivo, and is similar to a binding site
for the previously identified minisatellite DNA sequence binding protein (Msbp
1). The core DNA interacted in vitro with a protein that had an apparent
molecular mass of 40 kDa. These data indicate that the minisatellite DNA
represents the novel, chromatin-specific element in the mts1 complex enhancer.
PMID- 9654448
TI - Cation-regulated self-association of "synapsable" DNA duplexes.
AB - The simple innovation of introducing a block of G.G mismatches into a Watson
Crick DNA duplex permits two such duplexes, under conditions of physiological
temperature and salt, to "synapse" with one another at their G.G mismatch sites
via guanine-quartet formation. The short quadruplex formed at the "synapsed" site
necessarily has its strands in an antiparallel, or partially antiparallel
orientation. We wished to test whether a different, and more stable, synapsis
might be achieved if one of the two strands in the synapsable duplex had its
domain of guanine residues in a reverse orientation to the rest of the strand,
via 5'-5' and 3'-3' linkages. Such modified duplexes might synapse via the
formation of the thermodynamically preferred parallel quadruplex. Our results
indicate that such "parallel" and "antiparallel" synaptic events have
dramatically different requirements for cations. We use chemical probing
experiments to provide evidence for a kinetic model for this discrepancy. It may
be possible to exploit the distinct properties of the above two kinds of
synapsable duplexes for a variety of in vivo and in vitro applications.
PMID- 9654449
TI - Formation of amyloid-like fibrils by self-association of a partially unfolded
fibronectin type III module.
AB - The ninth type III module of murine fibronectin was expressed in E. coli and
folded into a compact homogeneous monomer whose unfolding and refolding were then
investigated by fluorescence, circular dichroism, calorimetry and electron
microscopy. The isolated module is unusually labile under physiological
conditions. When heated at 1 deg. C/minute it exhibits an irreversible
endothermic transition between 35 and 42 degrees C depending on the protein
concentration. The transition is accompanied by changes in secondary and tertiary
structure with partial exposure of the single tryptophan and increased binding of
the hydrophobic probe, 1,8-anilinonaphthalene-sulfonate. The partially unfolded
intermediate undergoes rapid self-association leading to the formation of large
stable multimers that, like the original monomer, contain substantial amounts of
beta sheet structure. The multimers melt and dissociate reversibly in a second
endothermic transition between 60 and 90 degrees C also depending on the protein
concentration. This second transition destroys the remaining secondary structure
and further exposes the tryptophan. Visualization of negatively stained specimens
in the electron microscope reveals that partially unfolded rmIII-9 slowly forms
amyloid-like fibrils of approximately 10 nm width and indeterminate length. A
subdomain swapping mechanism is proposed in which beta strands from one partially
unfolded molecule interact with complementary regions of another to form
oligomers and polymers. The possibility that similar interactions could play a
role in the formation of fibrils by fibronectin in vivo is discussed.
PMID- 9654450
TI - 1.8 A crystal structure of the major NAD(P)H:FMN oxidoreductase of a
bioluminescent bacterium, Vibrio fischeri: overall structure, cofactor and
substrate-analog binding, and comparison with related flavoproteins.
AB - We have solved the crystal structure of FRase I, the major NAD(P)H:FMN
oxidoreductase of Vibrio fischeri, by the multiple isomorphous replacement method
(MIR) at 1.8 A resolution with the conventional R factor of 0.187. The crystal
structure of FRase I complexed with its competitive inhibitor, dicoumarol, has
also been solved at 2.2 A resolution with the conventional R factor of 0.161.
FRase I is a homodimer, having one FMN cofactor per subunit, which is situated at
the interface of two subunits. The overall fold can be divided into two domains;
80% of the residues form a rigid core and the remaining, a small flexible domain.
The overall core folding is similar to those of an NADPH-dependent flavin
reductase of Vibrio harveyi (FRP) and the NADH oxidase of Thermus thermophilus
(NOX) in spite of the very low identity in amino acid sequences (10% with FRP and
21% with NOX). 56% of alpha-carbons of FRase I core residues could be superposed
onto NOX counterparts with an r.m.s. distance of 1.2 A. The remaining residues
have relatively high B-values and may be essential for defining the substrate
specificity. Indeed, one of them, Phe124, was found to participate in the binding
of dicoumarol through stacking to one of the rings of dicoumarol. Upon binding of
dicoumarol, most of the exposed re-face of the FMN cofactor is buried, which is
consistent with the ping pong bi bi catalytic mechanism.
PMID- 9654451
TI - Structure determination of the small ubiquitin-related modifier SUMO-1.
AB - The recently discovered small ubiquitin-related modifier SUMO-1 belongs to the
growing family of ubiquitin-related proteins involved in postranslational protein
modification. Unlike ubiquitin, SUMO-1 does not appear to target proteins for
degradation but seems to be involved in the modulation of protein-protein
interactions. Independent studies demonstrate an essential function of SUMO-1 in
the regulation of nucleo-cytoplasmic transport, and suggest a role in cell-cycle
regulation and apoptosis. Here, we present the first three-dimensional structure
of SUMO-1 solved by NMR. Although having only 18% amino acid sequence identity
with ubiquitin, the overall structure closely resembles that of ubiquitin,
featuring the betabetaalphabetabetaalphabeta fold of the ubiquitin protein
family. In addition, the position of the two C-terminal Gly residues required for
isopeptide bond formation is conserved between ubiquitin and SUMO-1. The most
prominent feature of SUMO-1 is a long and highly flexible N terminus, which
protrudes from the core of the protein and which is absent in ubiquitin.
Furthermore, ubiquitin Lys48, required to generate ubiquitin polymers, is
substituted in SUMO-1 by Gln69 at the same position, which provides an
explanation of why SUMO-1 has not been observed to form polymers. Moreover, the
hydrophobic core of SUMO-1 and ubiquitin is maintained by conserved hydrophobic
residues, whereas the overall charge topology of SUMO-1 and ubiquitin differs
significantly, suggesting specific modifying enzymes and target proteins for both
proteins.
PMID- 9654452
TI - Engineering activity and stability of Thermotoga maritima glutamate
dehydrogenase. I. Introduction of a six-residue ion-pair network in the hinge
region.
AB - Comparison of the recently determined three-dimensional structures of several
glutamate dehydrogenases allowed for the identification of a five-residue ion
pair network in the hinge region of Pyrococcus furiosus glutamate dehydrogenase
(melting temperature 113 degrees C), that is not present in the homologous
glutamate dehydrogenase from Thermotoga maritima (melting temperature 93 degrees
C). In order to study the role of this ion-pair network, we introduced it into
the T. maritima enzyme using a site-directed mutagenesis approach. The resulting
T. maritima glutamate dehydrogenases N97D, G376 K and N97D/G376 K as well as the
wild-type enzyme were overproduced in Escherichia coli and subsequently purified.
Elucidation of the three-dimensional structure of the double mutant N97D/G376 K
at 3.0 A, showed that the designed ion-pair interactions were indeed formed.
Moreover, because of interactions with an additional charged residue, a six
residue network is present in this double mutant. Melting temperatures of the
mutant enzymes N97D, G376 K and N97D/G376 K, as determined by differential
scanning calorimetry, did not differ significantly from that of the wild-type
enzyme. Identical transition midpoints in guanidinium chloride-induced
denaturation experiments were found for the wild-type and all mutant enzymes.
Thermal inactivation at 85 degrees C occured more than twofold faster for all
mutant enzymes than for the wild-type glutamate dehydrogenase. At temperatures of
65 degrees C and higher, the wild-type and the three mutant enzymes showed
identical specific activities. However, at 58 degrees C the specific activity of
N97D/G376 K and G376 K was found to be significantly higher than that of the wild
type and N97D enzymes. These results suggest that the engineered ion-pair
interactions in the hinge region do not affect the stability towards temperature
or guanidinium chloride-induced denaturation but rather affect the specific
activity of the enzyme and the temperature at which it functions optimally.
PMID- 9654454
TI - Editorial
AB - Copyright
PMID- 9654453
TI - A common ancestor for oxygenic and anoxygenic photosynthetic systems: a
comparison based on the structural model of photosystem I.
AB - The 4 A structural model of photosystem I (PSI) has elucidated essential features
of this protein complex. Inter alia, it demonstrates that the core proteins of
PSI, PsaA and PsaB each consist of an N-terminal antenna-binding domain, and a C
terminal reaction center (RC)-domain. A comparison of the RC-domain of PSI and
the photosynthetic RC of purple bacteria (PbRC), reveals significantly analogous
structures. This provides the structural support for the hypothesis that the two
RC-types (I and II) share a common evolutionary origin. Apart from a similar set
of constituent cofactors of the electron transfer system, the analogous features
include a comparable cofactor arrangement and a corresponding secondary structure
motif of the RC-cores. Despite these analogies, significant differences are
evident, particularly as regards the distances between and the orientation of
individual cofactors, and the length and orientation of alpha-helices. Inferred
roles of conserved amino acids are discussed for PSI, photosystem II (PSII),
photosystem C (PSC, green sulfur bacteria) and photosystem H (PSH,
heliobacteria). Significant sequence homology between the N-terminal, antenna
binding domains of the core proteins of type-I RCs, PsaA, PsaB, PscA and PshA (of
PSI, PSC and PSH respectively) with the antenna-binding subunits CP43 and CP47 of
PSII indicate that PSII has a modular structure comparable to that of PSI.
PMID- 9654455
TI - Microwave applications in neuromorphology and neurochemistry: safety precautions
and techniques.
AB - In science, the introduction of a new method is never easy, not even if it
concerns the use of a simple microwave oven. Most scientists do not realize the
numerous applications of microwave techniques. This paper gives a broad overview
of the application of microwave techniques in neuromorphology and neurochemistry,
starting with a historical overview ranging from the introduction of microwave
techniques as a scientific method in the 1970s to present. Organizations and
publication rules are highlighted in the next part. The effect of microwave
irradiation is discussed in two sections relating to microwave effects on the
whole organism and on the neuron. The main body of the paper discusses the
application of microwave techniques in the fields of neuromorphology and
neuropathology. The paper then presents aspects of microwave irradiation as
applied to ELISA techniques. In addition, cell fusion and cell reproduction under
microwave irradiation are discussed.
PMID- 9654456
TI - Problems and artifacts of microwave accelerated procedures in
neurohistotechnology and resolutions.
AB - Microwaving artifacts in histoprocessing and staining arise from the acceleration
of diffusional and reactive processes. Because such accelerations provide the
advantages of microwaving, and because microwave ovens cannot distinguish
desirable from undesirable accelerations, artifacts are inevitable. Such
microwaving problems can be categorized as follows: histoprocessing and staining
reagents may be lost or altered; staining targets may move away from their in
vivo sites, may be totally lost from the specimen, or may be altered; physical
characteristics such as permeability of specimens or embedding resins may be
changed; and staining processes themselves are sometimes different at elevated
temperatures. The most general tips for detecting and/or avoiding such problems
are to monitor and control the temperature of the reagents and the specimen, to
standardize the procedures, and to observe the specimen and reagents carefully
during microwaving when a new procedure is being introduced to the laboratory.
PMID- 9654457
TI - Calibration and standardization of microwave ovens for fixation of brain and
peripheral nerve tissue.
AB - Rapid and reproducible fixation of brain and peripheral nerve tissue for light
and electron microscopy studies can be done in a microwave oven. In this review
we report a standardized nomenclature for diverse fixation techniques that use
microwave heating: (1) microwave stabilization, (2) fast and ultrafast primary
microwave-chemical fixation, (3) microwave irradiation followed by chemical
fixation, (4) primary chemical fixation followed by microwave irradiation, and
(5) microwave fixation used in various combinations with freeze fixation. All of
these methods are well suited to fix brain tissue for light microscopy. Fast
primary microwave-chemical fixation is best for immunoelectron microscopy
studies. We also review how the physical characteristics of the microwave
frequency and the dimensions of microwave oven cavities can compromise microwave
fixation results. A microwave oven can be calibrated for fixation when the
following parameters are standardized: irradiation time; water load volume,
initial temperature, and placement within the oven; fixative composition, volume,
and initial temperature; and specimen container shape and placement within the
oven. Using two recently developed calibration tools, the neon bulb array and the
agar-saline-Giemsa tissue phantom, we report a simple calibration protocol that
identifies regions within a microwave oven for uniform microwave fixation.
PMID- 9654458
TI - Microwaves and heat in aldehyde fixation: model experiments with bovine serum
albumin.
AB - Most model experiments concerning tissue fixation have used low concentrations of
fixatives and proteins. Here, high concentrations (up to 32%) of bovine serum
albumin (BSA) were reacted with formaldehyde (1-20%) and glutaraldehyde (0.5-4%).
Gels were formed between 16% BSA and 10-20% formaldehyde at room temperature, but
not with percentages of formaldehyde lower than 4%. Microwave application or
heating in a water bath to 50 degrees C gave a gel from 1 to 20% formaldehyde.
Sixteen percent BSA also gave a gel with glutaraldehyde from 0.5 to 4%. Cone and
plate viscometry showed rapidly increasing viscosity at 4% formaldehyde and 16%
BSA at room temperature. At 50 degrees C, gels formed at a low concentration of
formaldehyde. Tissue fixation in which the local concentrations of protein may be
in excess of 30% is probably more complete than in vitro experiments in which low
concentrations of reagents have been used to permit subsequent spectrometry. This
was confirmed by polyacrylamide gel electrophoresis of liver.
PMID- 9654459
TI - Preservation and staining of myelinated nerve fibers.
AB - Six procedures are given for preservation of myelinated nerve fibers for light or
electron microscopic studies. These procedures fall into two main categories:
those with and those without aldehyde fixation. Essentially different effects are
attained by application of tannic acid, saline, microwave or conventional
heating, or a decreased temperature. All procedures end in osmication. Three main
aspects of myelinated fiber morphology are taken into account when judging the
quality of their preservation: axon, myelin sheath, and axon/myelin coherence.
Each aspect can be preserved excellently, but always in combination with a less
superior quality of the other two aspects. Superior myelin quality is attained
using microwave irradiation, either with aldehydes to which tannic acid is added
or without aldehyde fixatives. Superior axon quality is attained with aldehydes
and (conventional) heating. Axon/myelin coherence is best preserved by decreasing
the temperature during the rinse with saline. Another two procedures provide
good, though less superior, preservation of both axon and axon/myelin coherence.
Next, the fixed tissue is embedded in plastic blocks from which semithin and
ultrathin plastic sections are cut for light and electron microscopy,
respectively. In addition to the standard procedure for toluidine blue staining
on semithin sections, two microwave-supported procedures are described, which can
be used as alternatives if the staining result is unsatisfactory. Furthermore, a
toluidine blue staining procedure is described for glycol methacrylate (GMA)
embedded material, which can be used if larger sections are needed.
PMID- 9654460
TI - Antigen retrieval in formaldehyde-fixed human brain tissue.
AB - Microwave-stimulated antigen retrieval has become a widely accepted method in
both pathology and research laboratories. Since the introduction of the method in
1991, many groups have tried to optimize and standardize it. This review
describes the present state of the art. A standard method for microwave
stimulated antigen retrieval in formaldehyde-fixed paraffin-embedded and
nonembedded tissue is presented that results, in general, in very good staining
for antibodies used in neuroscience. However, there are still a few antigens that
are retrieved not at all or not in an optimal manner. Factors of importance for
microwave antigen retrieval are the pH of the retrieval solution and, related to
the pH, the temperature and duration of heating. These factors are discussed.
PMID- 9654461
TI - Microwave-stimulated Jones-Marres method for staining fungi in brain tissue of
immunocompromised patients.
AB - Life-threatening fungal infections have increased significantly in the past
decade due to the rising number of immunocompromised patients. Serological
diagnosis of most fungal infections is unreliable and blood cultures are positive
in only 50% of premortem cases; therefore, tissue sampling together with fast,
reliable staining of fungi should be carried out to reach the correct, timely
diagnosis. We developed, partly serendipitously, a microwave silver staining
method for fungi in histological sections. During a differentiation step in
periodic acid, background staining is removed. This rapid staining method can be
combined with immunostaining, for example, the alpha smooth muscle actin method,
to visualize blood vessels. Silver staining results were optimized using the
recently developed MicroMED BASIC microwave labstation for histology (Milestone
srl, Italy), featuring no-touch temperature measurements and PC control.
PMID- 9654462
TI - Cell replication rates and processes concerning antibody production in vitro are
not influenced by 2.45-GHz microwaves at physiologically normal temperatures.
AB - Several contradictory papers concerning the effects of microwaves on living
organisms and on in vitro cell suspensions have been published through the years.
These papers are difficult to interpret, because temperature measurement data are
often lacking. Reliable temperature measurements are important, because they
enable one to determine whether the observed microwave effects are thermal or
nonthermal. Therefore, a method was developed to investigate microwave effects on
cellular processes, in which the temperature was precisely monitored during
microwave treatment using a fiberoptic thermometer. This method involved the
processes required for in vitro production of monoclonal antibodies. Monoclonal
antibodies are vital ingredients in (microwave-stimulated) immunostaining
techniques and ELISAs, which have become important techniques in neuroscience.
The effects of 2.45-GHz microwaves on mouse myeloma and (neural) hybridoma cell
replication rates and on antibody production were investigated. In addition, the
effects on the cell fusion abilities of spleen lymphocytes and myeloma cells and
on in vitro immunization were studied. The results of this study show no effects
of microwaves on either of the processes mentioned using exposure times up to 5 h
a day at a physiologically normal temperature of 37 degrees C. It was concluded
that the effects of 2.45-GHz microwaves detected at higher temperatures are
thermal effects and that no indications for nonthermal 2.45-GHz microwave effects
exist under the exposure conditions used in the present study.
PMID- 9654463
TI - EPR and DNP properties of certain novel single electron contrast agents intended
for oximetric imaging.
AB - Parameters of relevance to oximetry with Overhauser magnetic resonance imaging
(OMRI) have been measured for three single electron contrast agents of the
triphenylmethyl type. The single electron contrast agents are stable and water
soluble. Magnetic resonance properties of the agents have been examined with
electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and
dynamic nuclear polarization (DNP) at 9.5 mT in water, isotonic saline, plasma,
and blood at 23 and 37 degreesC. The relaxivities of the agents are about 0.2-0.4
mM-1s-1 and the DNP enhancements extrapolate close to the dipolar limit. The
agents have a single, narrow EPR line, which is analyzed as a Voigt function. The
linewidth is measured as a function of the agent concentration and the oxygen
concentration. The concentration broadenings are about 1-3 microT/mM and the
Lorentzian linewidths at infinite dilution are less than 1 microT in water at
room temperature. The longitudinal electron spin relaxation rate is calculated
from the DNP enhancement curves. The oxygen broadening in water is about 50
microT/mM O2 at 37 degreesC. These agents have good properties for oximetry with
OMRI.
PMID- 9654464
TI - Pulse sequences for steady-state saturation of flowing spins.
AB - It is useful to be able to suppress the NMR signal from spins in a flowing fluid,
for example for "black-blood" visualization of blood vessels in vivo, for the
suppression of flow artifacts, and for the estimation of tissue perfusion by
continuous labeling of inflowing arterial spins. This work considers the flow of
fluid through a region in which it is subjected to a train of saturation pulses.
Computer simulations and in vitro measurements show that a train of equal
duration spoiler pulses produces less effective suppression than does a train of
pulses of geometrically increasing duration. It is shown analytically that a long
train of ideal equal-duration spoiler pulses converts initial magnetization (0,
0, M0) into a combination of longitudinal and transverse magnetization equal to
0. 29 (-M0, 0, M0) and is therefore unsatisfactory for continuous saturation.
PMID- 9654465
TI - Temporal characteristics of NMR signals from spin 3/2 nuclei of incompletely
disordered systems.
AB - Anisotropic nuclear quadrupole interactions can produce residual quadrupole
splitting in the NMR spectra of rapidly moving quadrupolar nuclei in incompletely
disordered aqueous heterogeneous systems. Such systems may include hydrated
sodium nuclei in biological tissue and biopolymer gels. To describe the NMR
signals from such samples, we use a domain model in which each domain is
characterized by a quadrupole frequency and a residence time of the nucleus. We
show that the signals from each domain after one pulse, the quadrupole echo
sequence, and the various multiple quantum filters (MQFs) can be expressed as a
linear combination of five different phase coherences. To simulate the effect of
various distributions (Pake powder pattern, Gaussian, etc.) of quadrupole
frequencies for different domains on the NMR signal, we have written the computer
program CORVUS. CORVUS also includes the effects of exchange between different
domains using diffusion and random jump models. The results of computer
simulations show that the Gaussian and Pake powder pattern quadrupole frequency
distributions produce very different phase coherences and observable NMR signals
when the exchange rate (1/taue) between different domains is slow. When 1/taue is
similar to the root mean square quadrupole frequency (final sigma), the signals
from the two distributions are similar. When 1/taue is an order of magnitude
greater than final sigma, there is no apparent evidence of quadrupole splitting
in the shape of the signal following one pulse, but the residual effects of the
quadrupole splitting make a significant contribution to the fast transverse
relaxation rate. Therefore, in this case, it is inappropriate to use the observed
biexponential relaxation rates to obtain a single correlation time. The
quadrupole echo and the various MQF signals contain an echo from the satellite
transitions in the presence of quadrupole splitting. The peak of this echo is
very sensitive to 1/taue. The time domain analysis of these signals is more
direct and less ambiguous than the frequency domain analysis because the echo
does not occur at the beginning of data acquisition. The quadrupole echo pulse
sequence is the most sensitive detector of residual quadrupole splitting and
exchange of sodium ions between different domains. However, if the sample is
compartmentalized so that only a fraction of the nuclei have quadrupole
splitting, the double quantum magic angle filter (DQ-MA) is more suitable. This
is because the DQ-MA signal contains only the contributions from satellite
transitions. Use of simulations to analyze signals from various one-pulse,
quadrupole echo, and multiple quantum filter pulse sequences can yield
information on substrate order and aid in quantitation of multiple quantum filter
signals.
PMID- 9654466
TI - Detection of proton chemical exchange between metabolites and water in biological
tissues.
AB - Metabolites in proton chemical exchange with water were detected via the water
proton signal using saturation transfer techniques in model systems and
biological tissues. The metabolites were selectively saturated and the resulting
decrease in the much larger water proton pool was used to monitor the metabolite.
This indirect detection scheme can result in a several orders of magnitude
increase in sensitivity for metabolites over direct detection methods. A control
irradiation scheme was devised to compensate for macromolecular/water
magnetization transfer. Using this approach, significant chemical exchange
regions at approximately 1 and 2.5 ppm were detected in kidney medulla. Using a
difference imaging technique between a control irradiation above (-1.74 ppm) and
below (+1.74 ppm) the water resonance, a chemical exchange image of the kidney
was calculated. These data revealed a linear gradient of chemical exchange
increasing from the cortex to the medulla. Studies on medullary acid extracts and
urine revealed that the exchange observed in the kidney was predominantly with
low molecular weight metabolites. Urea (1 ppm) was identified as contributing to
the kidney/urine chemical exchange; however, other unidentified metabolites may
also contribute to this effect. These studies demonstrate that tissue metabolites
can be detected and imaged via the water protons using the signal amplification
properties of saturation transfer in the presence of water/macromolecule
magnetization transfer.
PMID- 9654467
TI - Two-dimensional nuclear-Zeeman-resolved electron spin echo envelope modulation
(NZ-ESEEM) spectroscopy.
AB - A two-dimensional electron spin echo envelope modulation (ESEEM) experiment,
called nuclear-Zeeman-resolved ESEEM (NZ-ESEEM), that correlates nuclear
transition frequencies with nuclear Zeeman frequencies is introduced. NZ-ESEEM is
basically a three-pulse ESEEM experiment complemented by a magnetic-field pulse
applied during part of the free evolution period between the second and third
microwave pulse. The inner working of the new approach is explained and the
instrumentation is discussed. The capacity of the method is illustrated by two
examples of applications.
PMID- 9654468
TI - NMR temperature measurements using a paramagnetic lanthanide complex.
AB - NMR thermometry has previously suffered from poor thermal resolution owing to the
relatively weak dependence of chemical shift on temperature in diamagnetic
molecules. In contrast, the shifts of nuclear spins near a paramagnetic center
exhibit strong temperature dependencies. The chemical shifts of the thulium
1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) complex
(TmDOTP5-) have been studied as a function of temperature, pH, and Ca2+
concentration over ranges which may be encountered in vivo. The results
demonstrate that the 1H and 31P shifts in TmDOTP5- are highly sensitive to
temperature and may be used for NMR thermometry with excellent accuracy and
resolution. A new technique is also described which permits simultaneous
measurements of temperature and pH changes from the shifts of multiple TmDOTP5-
spectral lines.
PMID- 9654469
TI - Resolution enhancement in multiple-quantum MAS NMR spectroscopy.
AB - Two techniques for resolution and sensitivity enhancement are introduced in
multiple-quantum (MQ) MAS spectroscopy of rigid solids. The first makes use of
ultrafast MAS with spinning frequencies of up to 35 kHz, while the second
combines MAS at moderately fast spinning frequencies of about 13 kHz with
multiple-pulse (MP) dipolar decoupling. For the latter approach, a semiwindowless
WHH-4 sequence is applied during the MQ evolution period (MQ dimension) and/or
detection period (single-quantum dimension). In the MQ dimension, the MP sequence
has to be supplemented by two bracketing pulses in order to preserve the order
and the intensities of the evolving MQ coherences. Double-quantum 1H NMR spectra
of l-alanine recorded using both decoupling techniques are shown and compared to
each other. Triple-quantum 1H NMR spectra under ultrafast MAS conditions are also
presented.
PMID- 9654470
TI - Spectral editing technique for the in vitro and in vivo detection of taurine.
AB - In vivo 1H NMR spectroscopy has proven to be a useful noninvasive tool for the
investigation of numerous metabolic and physiological states. Taurine is
potentially a useful indicator in neonate development and is involved in a number
of physiological processes. However, it could not previously be observed in the
in vivo 1H spectrum because of overlap with adjacent resonances. We have
developed a spectral editing technique based upon double quantum filtration which
allows the taurine resonances to be resolved from adjacent peaks. The experiment
is demonstrated both on perchloric acid rodent brain extract and on rodent brain
homogenate.
PMID- 9654471
TI - Relaxation time determinations by progressive saturation EPR: effects of
molecular motion and Zeeman modulation for spin labels.
AB - The EPR spectra of nitroxide spin labels have been simulated as a function of
microwave field, H1, taking into account both magnetic field modulation and
molecular rotation. It is found that the saturation of the second integral, S, of
the first harmonic in-phase absorption spectrum is approximated by that predicted
for slow-passage conditions, that is, S approximately H1/1 + PH21, in all cases.
This result is independent of the degree of inhomogeneous broadening. In general,
the fitting parameter, P, depends not only on the T1 and T2 relaxation times, but
also on the rate of molecular reorientation and on the modulation frequency.
Calibrations for determining the relaxation times are established from the
simulations. For a given modulation frequency and molecular reorientation rate,
the parameter obtained by fitting the saturation curves is given by 1/P = a +
1/gamma2eT1 . Teff2, where Teff2 is the effective T2. For molecular reorientation
frequencies in the range 2 x 10(7)-2 x 10(8) s-1, Teff2 is dominated by the
molecular dynamics and is only weakly dependent on the intrinsic T02, allowing a
direct estimation of T1. For reorientation frequencies outside this range, the
(T1T2) product may be determined from the calibrations. The method is applied to
determining relaxation times for spin labels undergoing different rates of
rotational reorientation in a variety of environments, including those of
biological relevance, and is verified experimentally by the relaxation rate
enhancements induced by paramagnetic ions.
PMID- 9654472
TI - Investigating catalytic processes with parahydrogen: evolution of zero-quantum
coherence in AA'X spin systems
AB - A systematic outline for the elucidation of the nature of hydrogenation
intermediates with a lifetime too short to be directly detectable with standard
NMR methods is presented. The method takes advantage of the special nature of the
parahydrogen density operator and its inherent enhancement factor. The key aspect
of these experiments is the evolution of zero-quantum coherence which is
contained in the parahydrogen density operator. Analytical coherence transfer
functions have been derived which describe the evolution of this zero-quantum
coherence in spin systems consisting of three spins 1/2 that form an AA'X spin
system. The analytical expressions presented form a basis for a thorough
investigation of crucial catalytic steps. Copyright 1998 Academic Press.
PMID- 9654473
TI - Lithium visibility in rat brain and muscle in vivo by 7Li NMR imaging.
AB - The apparent concentration of lithium (Li) in vivo was determined for several
regions in the brain and muscle of rats by 7Li NMR imaging at 4.7 T with
inclusion of an external standard of known concentration and visibility. The
average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for
various brain regions under the dosing conditions used. The results were compared
to concentrations determined in vitro by high-resolution 7Li NMR spectroscopy of
extracts of brain and muscle tissue from the same rats. The comparison provided
estimates of the 7Li NMR visibility of the Li cation in each tissue region.
Although there was considerable scatter of the calculated visibilities among the
five rats studied, the results suggested essentially full visibility (96%) for Li
in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.
PMID- 9654474
TI - Optimizing the 13C-14N REAPDOR NMR experiment: a theoretical and experimental
study.
AB - The optimum 14N pulse lengths in the 13C-14N rotational-echo adiabatic-passage
double-resonance (REAPDOR) NMR experiment are determined from calculations and
from experiments on samples of glycine and L-alanine. The REAPDOR experiment
utilizes the adiabatic passages that 14N spins make between the 14N Zeeman energy
levels during the application of a single, short 14N radiofrequency pulse. Use of
a short 14N irradiation time of less than one-quarter of a rotor period ensures
that the number of 14N spins that undergo more than one passage is minimized.
This simplifies calculations describing 13C dipolar dephasing and provides better
agreement between calculations and experiments. Recovery of the 13C-14N dipolar
couplings and 14N quadrupolar coupling constants and asymmetry parameters is
described.
PMID- 9654475
TI - Monitoring local disposition kinetics of carboplatin in vivo after subcutaneous
injection in rats by means of 195Pt NMR.
AB - The anticancer drug carboplatin has been monitored in rats during treatment by
means of in vivo 195Pt NMR spectroscopy at 2.0 T. The purpose of the study was to
assess local disposition kinetics in intact tissue following subcutaneous
injection of a platinum-containing drug. Serial 195Pt NMR measurements have been
carried out in four animals after administration of carboplatin solutions with
doses ranging from 37.1 to 59.4 mg per kg body weight. A surface coil of 2 cm
diameter tuned to 18.3 MHz was placed over the injection site (back of the neck
of the animals). To optimize measurement parameters of the single-pulse-acquire
sequence and to determine chemical shifts and the detection threshold, in vitro
195Pt NMR experiments have been performed on model solutions of potassium
tetrachloroplatinate(II), carboplatin, and cisplatin with different solvents such
as H2O, DMSO, and DMF. Resonances of PtCl2-4, carboplatin, cisplatin, and cis
[Pt(NH2)Cl(DMSO)]+ were observed at chemical shift positions delta = -1623 ppm,
1705 ppm, -2060 ppm (cisplatin in DMSO), and -3120 ppm, respectively, relative to
the reference signal of Na2PtCl6 at delta = 0 ppm. A spin-lattice relaxation time
of carboplatin of T1 = (0.103 +/- 0.02) s was measured. The threshold for NMR
detection of platinum-containing compounds estimated from the in vitro
experiments was 10 micromol (corresponding to approximately 4.8 mM). In vivo
195Pt NMR spectra obtained in four rats after administration of carboplatin
showed a broad resonance at delta = -(1715 +/- 8) ppm. The signal-to-noise ratio
of this peak (starting 2 min after the injection) was approximately 9:1 for a
measurement time of 6 min (TR= 13 ms, 28672 transients). The elimination rate
constant of local disposition of carboplatin was kel = 0.017 (0.008-0.025) min-1
(median and range).
PMID- 9654476
TI - Five-quantum coherence of I = 52 nuclei: 27Al in an Al2O3 single crystal
AB - Optimal conditions were calculated for excitation and detection of the five
quantum coherence of quadrupolar nuclei with I = 52 in single crystals, observed
by the two-pulse sequence (theta1)x - tau1 - (theta2)alpha - tau2, where alpha is
the phase cycling angle. Variations in the pulse lengths, the relative values of
the nutation frequency omega1 = gammaB1, and the quadrupolar frequency omegaQ as
well as in the resonance offset were taken into account. In addition, the effect
of the pulse length on the intensity of spectral lines was considered.
Theoretical results were compared with experiments on 27Al nuclei in an Al2O3
single crystal. Copyright 1998 Academic Press.
PMID- 9654477
TI - Mapping molecular orientation in solids by rotating-frame NQR techniques
AB - A multi-dimensional NQR technique to image both the spatial distribution of
quadrupolar nuclei and the local orientation of the electric field gradient
tensor at the quadrupole sites in solids is reported. The encoding procedure is
based on the irradiation of the sample by a pulse sequence composed of spatially
homogeneous and inhomogeneous radiofrequency fields. A method that encodes the
spatial and orientation information in the amplitudes of the free-induction decay
signals and a proper three-dimensional reconstruction procedure that yields the
space-orientation-dependent NQR spectra are described. A two-dimensional variant
allows rapid measurement of the spatially dependent orientation distribution of
molecules, disregarding the spectroscopic information. Copyright 1998 Academic
Press.
PMID- 9654479
TI - Earth's field NMR in antarctica: A pulsed gradient spin echo NMR study of
restricted diffusion in sea Ice
AB - We report on the use in Antarctica of a nuclear magnetic resonance spectrometer
which utilizes the terrestrial magnetic field. Free induction decay data are used
to obtain estimates of brine content, in samples of sea ice extracted from the
annual ice of McMurdo Sound, in the vicinity of Cape Evans, Ross Island. Pulsed
gradient spin echo experiments were performed on these samples in which the
orientation of the gradient with respect to the ice growth axis was varied and
the separation time between the gradient pulses was varied. Anisotropic
restricted diffusion effects are apparent and we use these to tentatively model
the brine pocket morphology. Copyright 1998 Academic Press.
PMID- 9654478
TI - An adiabatic multiple spin-echo pulse sequence: removal of systematic errors due
to pulse imperfections and off-resonance effects.
AB - Application of AFP (adiabatic fast passage) pulses for removal of systematic
errors associated with multiple spin-echo sequences is demonstrated. The
adiabatic fast passage pulses facilitate minimization of cumulative pulse errors
for all three components of magnetization. It is also shown that off-resonance
effects present in conventional CPMG sequences which degrade image quality in
magnetic resonance imaging and introduce systematic errors in measured T2
relaxation time peak amplitudes can be suppressed by introduction of AFP pulses
without any degradation of overall signal intensity. The technique has been
tested on the 15N spin-spin relaxation time measurements of a 110 amino acid
domain of the F-actin cross-linking protein.
PMID- 9654480
TI - Alignment echo of spin-3/2 9Be nuclei: detection of ultraslow motion
AB - It is demonstrated that the alignment echo of 9Be is quite useful for detecting
ultraslow atomic motions in the metallic glass Zr46. 75Ti8.25Cu7.5Ni10Be27.5. The
time scale of detectable atomic motion is between T2 = 1.5 ms and T1 of a few
seconds. Similar to previous works of 2H NMR, the Jeener-Broekaert sequence is
used to create quadrupolar order for spin-32 nuclei upon nonselective
excitations. Since the chemical and Knight shift distributions are not negligible
for 9Be, the proper choice of the dephasing time between the first and the second
pulses is essential for achieving pure quadrupolar order. It is demonstrated
experimentally that slow atomic motions contribute significantly to the decay of
the alignment echo near the glass transition temperature. Copyright 1998 Academic
Press.
PMID- 9654481
TI - Simplification of 19F NMR spectra of liquid crystalline samples by multiple-pulse
COSY experiments
AB - A general method is presented of converting second-order fluorine-19 spectra of
liquid crystalline samples into first-order spectra. This is achieved by
recording a 19F COSY spectrum with a multiple pulse dipolar reducing sequence
(MPS) operating in the t1 period, leading to a F1 projection which is first
order. The method is illustrated by recording spectra on a sample of 1,3-dichloro
4-fluorobenzene dissolved in the nematic solvent ZLI 1167. Experiments have been
done in which the MPS is either the MREV-8 or Flip-Flop-16 sequence. The first
order F1 projections are analyzed to give reduced total 1H-19F couplings,
KCSTHFij and the reduction factors, KCS, are obtained by comparison with the
THFij available from an analysis of the ordinary 1D spectrum. The reduction
factors are compared with values predicted by average Hamiltonian theory (AHT).
The reasons for the differences found between observed and predicted values of
KCS have been investigated by performing numerical simulations of the 2D MPS COSY
experiments. Copyright 1998 Academic Press.
PMID- 9654482
TI - In-phase double selective excitation of coupled spin systems using excitation
sculpting
AB - An experiment that excites exclusively coupled nuclei pairsis presented. It
involves the biselective defocusing and refocusing of coupled transverse
magnetization under double pulsed field gradient spin echo conditions.
Application to the extraction of subspectra from crowded COSY spectra is
presented, as well as a doubly selective version of the homonuclear J-resolved
experiment. Copyright 1998 Academic Press.
PMID- 9654483
TI - High magnetic field gradient PGSE NMR in the presence of a large polarizing field
AB - A description is given of pulsed gradient spin echo (PGSE) NMR experiments in
which large pulsed magnetic field gradients may be required. The design
contraints are discussed and, in particular, the problem of the use of large
pulsed magnetic field gradients in conjunction with large polarizing fields is
considered. Issues addressed concern probe mechanical assembly, current supply
requirements, and pulse shape design. We describe a quadrupolar coil with a
gradient amplitude of 1.65 T m-1 A-1 which has been used successfully up to a
maximum gradient of around 40 T m-1. A diffusion coefficent of 7.5 x 10(-16) m2 s
1 has been measured using this system, the lowest yet achieved by PGSE NMR
methods. Copyright 1998 Academic Press.
PMID- 9654484
TI - Coherence selection and excitation sculpting using RF-gradients in selective 1D
experiments and nonselective 2D experiments
AB - The B0 gradient pulses can be replaced with long high-power pulses (RF-gradients)
in z-rotation composite sandwiches. By doing this, practically all B0 gradient
based pulse sequences can be performed with instruments lacking a field gradient
accessory. We have implemented RF-gradients into selective 1D and nonselective 2D
TOCSY and NOESY experiments. The spectral quality obtained with the RF-gradient
method was comparable to that of the B0 method for small- to medium-sized
molecules. There are also some advantages in using RF-gradients instead of B0
gradients. There is practically no shift or coupling evolution during RF-gradient
pulses. This may be significant in some experiments. Copyright 1998 Academic
Press.
PMID- 9654485
TI - A high-pressure, high-resolution NMR probe for experiments at 500 MHz.
AB - A novel high-pressure, high-resolution NMR probe is described which operates at a
frequency of 500 MHz. The design features an alternative RF coil (8 mm sample
tube) for high frequency, sensitivity, probe power, and resolution (< 3.0 x 10(
9)). The probe is capable of pressures to at least 5 kbar over a temperature
range of -30 to 80 degreesC, and has a double-tuned 1H/2H circuit which can tune
at 1H frequencies of either 300 or 500 MHz. The sensitivity of the 300-MHz
circuit is over twice that of previous 10-mm high-pressure NMR probe designs,
while at 500 MHz the sensitivity is nearly five times that of previous 300-MHz
pressure probes. Potential biochemical applications are demonstrated by 2D NOESY
spectra of a Troponin C mutant.
PMID- 9654486
TI - A novel composite 90 degrees pulse sequence which provides distortionless NMR
spectra and suppresses without destroying the water magnetization.
AB - A novel 90 degrees composite pulse sequence which allows one to record 1D and 2D
NMR spectra without disturbing the water magnetization is described. A home
written program was used to optimize the pulse angles for which the pulse
sequence response fitted best the desired excitation profile, producing a neat
and distortionless spectrum with a broad null excitation at the carrier
frequency. The resulting pulse sequence was first evaluated using the simulation
program "PENCIL" and then tested on two protein samples. A 3.5 degrees phase
shift of the last pulse was required to cancel correctly the water signal. The
pulse scheme was appended to a NOESY pulse sequence. Inspection of the water
cross section revealed interactions between water and some protons of
drosomycine, a small insect antifungal protein.
PMID- 9654487
TI - Fast broadband inversion by adiabatic pulses.
AB - Despite the advantages of compensation for resonance offset and B1 inhomogeneity,
adiabatic pulses are not yet in general use in high-resolution NMR, often because
of the conception that these pulses require longer time or increased power to
perform. We show that adiabatic pulses with tangential frequency sweeps and other
frequency-modulation functions can be optimized to accomplish 13C and 1H
broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at
B1 strengths available with modern high-resolution probes.
PMID- 9654488
TI - A simple one-dimensional solid-state NMR method to characterize the nuclear spin
interaction tensors associated with the peptide bond.
AB - We propose a simple one-dimensional RF pulse sequence for the study of chemical
shift and heteronuclear dipolar coupling tensors of oriented as well as
unoriented solids. An off-resonance RF decoupling of protons during the signal
acquisition of less sensitive nuclei is used to suppress homonuclear 1H-1H
dipolar interactions. This method is experimentally demonstrated on peptide
samples selectively labeled with 15N isotope.
PMID- 9654489
TI - Distributions of the quadrupolar and isotropic chemical shift interactions in two
dimensional multiple-quantum MAS NMR spectra
AB - The distributions of both the quadrupolar and the isotopic chemical shift
interactions are shown to give multiple-quantum MAS spectra that remain tilted
after shearing. For both types of distribution, the theoretical slopes, formed by
the resulting distribution of the centers of gravity of the signals, are
calculated. Copyright 1998 Academic Press.
PMID- 9654490
TI - Automated shimming with normal spectrometer hardware: 3D profile edge shimming
AB - A novel method is proposed for automated magnetic field homogeneity adjustment in
high-resolution NMR. The method uses measurements of the edge frequencies of
slice profiles recorded under static gradients to obtain three-dimensional
magnetic field maps and does not require significant extra spectrometer hardware.
Results are presented for the "cold" shimming of 5- and 10-mm-diameter probes in
a 400-MHz narrow bore magnet. Copyright 1998 Academic Press.
PMID- 9654491
TI - A robust method for determining the magnitude of the fully asymmetric alignment
tensor of oriented macromolecules in the absence of structural information.
AB - It has recently been shown that the degree of alignment of macromolecules in an
aqueous dilute liquid crystalline medium of bicelles is sufficient to permit
accurate values of residual 15N-1H, 13C-1H, and 13Calpha-C' dipolar couplings to
be obtained on a routine basis, thereby providing potentially unique long-range
structural information. To make use of this information in macromolecular
structure determination, the magnitude of the axial and rhombic components of the
molecular alignment tensor must be determined. This can be achieved by taking
advantage of the fact that different, fixed-distance internuclear vector types
are differently distributed relative to the alignment tensor. A histogram of the
ensemble of normalized residual dipolar couplings for several such vector types
approximates a powder pattern from which the magnitude of the axial and rhombic
components are readily extracted in the absence of any prior structural
information. The applicability of this method is demonstrated using synthetic
data derived from four proteins representative of different sizes, topologies,
and secondary structures, and experimental data measured on the small protein
ubiquitin.
PMID- 9654492
TI - Information from the water stripe in TOCSY experiments on systems with
exchangeable protons.
AB - The water "stripes" of the TOCSY maps of aqueous solutions of sucrose, of a 15
aminoacid peptide, and of several of the constituent aminoacids are shown to
contain correlations at the resonance frequencies of protons which are scalar
coupled to OH or NH protons which exchange with the solvent. Theoretical analysis
of chemical exchange during the spin-lock period in TOCSY elucidates the origin
of these correlations, and shows that their intensities vary with the duration of
the spin-lock period and with the exchange rate.
PMID- 9654493
TI - RF microcoil design for practical NMR of mass-limited samples.
AB - This paper addresses practical issues involved in obtaining high resolution 1H
NMR spectra from samples containing less than 10 nmol. Solenoidal microcoils have
been constructed to: (a) assess the effects of magnetic susceptibility mismatches
at 500 MHz, (b) increase the concentration sensitivity of microcoil probes, (c)
incorporate a lock channel for 2D experiments and long 1D acquisitions, and (d)
assess the total amount of the sample required (with respect to the coil length)
to avoid line broadening due to edge effects. Compared to previously published
microcoil results, sample volumes have been increased by a factor of 20 with a
concomitant decrease in the required concentration (5-20 mM). Perfluorocarbon
susceptibility matching remained effective at 500 MHz, allowing acquisition of
high resolution NMR spectra. A lock channel has also been successfully
incorporated in microcoil probes. The limits of detection for sucrose with a 10
min acquisition time were found to be 17.8 and 34.1 pmol for the single and
double resonance coils, respectively. A sample length of approximately 10 times
than that of the coil was required to avoid magnetic susceptibility artifacts.
PMID- 9654494
TI - Detection of phosphomonoester signals in proton-decoupled 31P NMR spectra of the
myocardium of patients with myocardial hypertrophy.
AB - Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular
myocardium was used to monitor myocardial phosphate metabolism in asymptomatic
patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS,
n = 12). In addition to the well-known phosphorus signals a phosphomonoester
(PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This
signal was not observed in the spectra of normal controls (n = 11). We suggest
that in spectra of patients with myocardial hypertrophy the presence of a PME
signal reflects alterations in myocardial glucose metabolism.
PMID- 9654496
TI - Meetings calendar
AB - Copyright
PMID- 9654495
TI - Measurement of carbon-phosphorus J coupling constants in RNA using spin-echo
difference constant-time HCCH-COSY.
AB - We report a novel NMR technique for the measurement of carbon-phosphorus coupling
constants in RNA oligomers. This method, spin-echo difference constant-time HCCH
COSY, takes advantage of the well-dispersed H1' and C1' resonances to analyze
couplings involving the more poorly dispersed ribose carbon and phosphorus
resonances. The technique was applied to analysis of the 3JC2'P coupling
constants related to backbone epsilon torsion angles in a 30-nucleotide lead
dependent ribozyme. 3JC2'P coupling constants were obtained for approximately 90%
of the residues in this RNA, which is over twice as many as could be obtained
with previous methods.
PMID- 9654535
TI - A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine
Study Group.
AB - BACKGROUND AND METHODS: In preliminary trials, lamivudine, an oral nucleoside
analogue, has shown promise for the treatment of chronic hepatitis B. We
conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients
with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of
lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally
once daily. The patients underwent liver biopsies before entering the study and
after completing the assigned treatment regimen. The primary end point was a
reduction of at least two points in the Knodell necroinflammatory score. RESULTS:
Hepatic necroinflammatory activity improved by two points or more in 56 percent
of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25
mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001,
respectively, for the comparisons of lamivudine treatment with placebo).
Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg
of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those
receiving placebo. The 100-mg dose of lamivudine was associated with a reduced
progression of fibrosis (P=0.01 for the comparison with placebo) and with the
highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg,
development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the
greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with
the base-line value), and the highest rate of sustained normalization of alanine
aminotransferase levels (72 percent). Ninety-six percent of the patients
completed the study. The incidence of adverse events was similar in all groups,
and there were few serious events. CONCLUSIONS: In a one-year study, lamivudine
was associated with substantial histologic improvement in many patients with
chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose
of 25 mg.
PMID- 9654536
TI - Reversal of lesions of diabetic nephropathy after pancreas transplantation.
AB - BACKGROUND: In patients with type I diabetes mellitus who do not have uremia and
have not received a kidney transplant, pancreas transplantation does not
ameliorate established lesions of diabetic nephropathy within five years after
transplantation, but the effects of longer periods of normoglycemia are unknown.
METHODS: We studied kidney function and performed renal biopsies before pancreas
transplantation and 5 and 10 years thereafter in eight patients with type I
diabetes but without uremia who had mild to advanced lesions of diabetic
nephropathy at the time of transplantation. The biopsy samples were analyzed
morphometrically. RESULTS: All patients had persistently normal glycosylated
hemoglobin values after transplantation. The median urinary albumin excretion
rate was 103 mg per day before transplantation, 30 mg per day 5 years after
transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the
comparison of values at base line and at 5 years; P=0.11 for the comparison
between base line and 10 years). The mean (+/-SD) creatinine clearance rate
declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base
line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per
minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and
tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm,
respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had
decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and
P=0.004 for the comparisons with the base-line values). The mesangial fractional
volume (the proportion of the glomerulus occupied by the mesangium) increased
from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased
at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and
P=0.006 for the comparison with the value at 5 years), mostly because of a
reduction in mesangial matrix. CONCLUSIONS: Pancreas transplantation can reverse
the lesions of diabetic nephropathy, but reversal requires more than five years
of normoglycemia.
PMID- 9654537
TI - Lack of effect of walking on labor and delivery.
AB - BACKGROUND AND METHODS: Walking during labor may reduce patients' discomfort and
improve outcomes. We conducted a randomized trial of walking during active labor
to determine whether it altered the duration of labor or other maternal or fetal
outcomes. Women with uncomplicated pregnancies between 36 and 41 weeks' gestation
and in active labor were randomly assigned either to walking or to no walking
(usual care). Pedometers were used to quantify walking, and the time spent
walking was recorded. RESULTS: Of the 536 women assigned to the walking group,
380 actually walked. Their mean (+/-SD) walking time was 56+/-46 minutes. There
were no significant differences between the women assigned to the walking group
and the 531 women assigned to the usual-care group in the duration of the first
stage of labor (6.1 hours in both groups, P=0.83), the need for labor
augmentation with oxytocin (23 percent vs. 26 percent, P=0.25), and the use of
analgesia (84 percent vs. 86 percent, P=0.59). Similarly, the percentages of
women requiring delivery by forceps (4 percent vs. 3 percent, P=0.35) and
cesarean section (4 percent vs. 6 percent, P=0.25) were not significantly
different. These labor and delivery outcomes were unrelated to walking in both
nulliparous and parous women. The infants' outcomes were also similar in the two
study groups. CONCLUSIONS: Walking neither enhanced nor impaired active labor and
was not harmful to the mothers or their infants.
PMID- 9654538
TI - Enoxaparin plus compression stockings compared with compression stockings alone
in the prevention of venous thromboembolism after elective neurosurgery.
AB - BACKGROUND: Compression stockings are recommended for prophylaxis against venous
thromboembolism in patients undergoing neurosurgery, but anticoagulant agents
have not gained wide acceptance because of concern about intracranial bleeding.
METHODS: In a multicenter, randomized, double-blind trial, we assessed the
efficacy and safety of enoxaparin in conjunction with the use of compression
stockings in the prevention of venous thromboembolism in patients undergoing
elective neurosurgery. Enoxaparin (40 mg once daily) or placebo was given
subcutaneously for not less than seven days beginning within 24 hours after the
completion of surgery. The primary end point was symptomatic, objectively
confirmed venous thromboembolism or deep-vein thrombosis assessed by bilateral
venography, which was performed in all patients on day 8+/-1. Bleeding side
effects were carefully assessed. RESULTS: Among the 307 patients assigned to
treatment groups, 129 of the 154 patients receiving placebo (84 percent) and 130
of the 153 patients receiving enoxaparin (85 percent) had venographic studies
adequate for analysis. An additional patient in the placebo group died before
venography of autopsy-confirmed pulmonary embolism. In this analysis, 42 patients
given placebo (32 percent) and 22 patients given enoxaparin (17 percent) had deep
vein thrombosis (relative risk in the enoxaparin group, 0.52; 95 percent
confidence interval, 0.33 to 0.82; P=0.004). The rates of proximal deep-vein
thrombosis were 13 percent in patients receiving placebo and 5 percent in
patients receiving enoxaparin (relative risk in the enoxaparin group, 0.41; 95
percent confidence interval, 0.17 to 0.95; P=0.04). Two patients in the placebo
group died of autopsy-confirmed pulmonary embolism on days 9 and 16. Major
bleeding occurred in four patients receiving placebo (intracranial bleeding in
all four) and four patients (intracranial bleeding in three) receiving enoxaparin
(3 percent of each group). CONCLUSIONS: Enoxaparin combined with compression
stockings is more effective than compression stockings alone for the prevention
of venous thromboembolism after elective neurosurgery and does not cause
excessive bleeding.
PMID- 9654539
TI - Images in clinical medicine. Floating right atrial thrombus and massive pulmonary
embolism.
PMID- 9654540
TI - Shattuck lecture--medicine and the media.
PMID- 9654541
TI - Pulmonary embolism.
PMID- 9654543
TI - Treatment of chronic hepatitis B infection.
PMID- 9654544
TI - Pancreas transplantation and diabetic complications.
PMID- 9654545
TI - Managing labor--never walk alone.
PMID- 9654548
TI - Evaluation of the international academic activities of members of the japanese
orthopaedic association
PMID- 9654547
TI - Human cloning and the challenge of regulation.
PMID- 9654549
TI - Factors influencing lumbar spine bone mineral density assessment by dual-energy X
ray absorptiometry: comparison with lumbar spinal radiogram.
AB - A study was conducted to determine the effect of radiographic findings of lumbar
spinal changes upon bone mineral density measurements obtained by dual energy X
ray absorptiometry (DXA). Four hundred subjects were chosen from among 1543
community residents, aged 40-79 years. Study groups of 50 subjects each were
selected by sex and 10-year age groups. This study investigated 390 of the 400
subjects who agreed to the conduct of spine bone mineral density measurement and
spinal radiography. Lumbar spine radiograms were examined for findings of
osteophyte formation, facet joint osteoarthritis, vertebral fracture, and aortic
calcification. The prevalence of osteophyte formation, facet joint
osteoarthritis, vertebral fracture, and aortic calcification increased with age
in both men and women. On multiple regression analysis, bone mineral density was
significantly higher (P < 0.001) in subjects with osteophyte formation or facet
joint osteoarthritis than in those without these conditions, while bone mineral
density was significantly lower in subjects with vertebral fracture. This study
demonstrated that osteophyte formation, facet joint osteoarthritis, and vertebral
fracture should be taken into account in the evaluation of bone mineral density
by DXA in people in older age groups, since these conditions occur at a
considerable rate in such subjects.
PMID- 9654550
TI - Magnetic resonance imaging of anterior cruciate ligament (ACL) tears: diagnostic
value of ACL-tibial plateau angle.
AB - Tears of the anterior cruciate ligament (ACL) are often difficult to diagnose on
magnetic resonance imaging (MRI), as it is often difficult to interpret the
images. We developed a quantitative method for diagnosing ACL tears on MRI; the
method involves measuring the angle formed by the intersection between a straight
line drawn along the anterior border of the ACL and a straight line drawn along
the medial tibial plateau (AT angle) on MRI. The AT angle was measured by two
orthopedic surgeons approved by the Japanese Orthopedic Association and one
orthopedic resident, none of whom had any prior knowledge of the physical and
arthroscopic findings of the patients. Measurements were performed in 30 knees
with ACL tears and 57 knees without tears. There was no significant difference
between the AT angles measured by the three examiners in either the group with
ACL tears or that without ACL tears. The mean value of the AT angle in the torn
ACL group (33.9 +/- 1.1 degrees) was significantly smaller than that in the
intact ACL group (52.3 +/- 1.0 degrees; mean +/- SE). When 45 degrees or less was
set as the criterion defining a tear of the ACL, the diagnostic accuracy of our
method was 87.4%; sensitivity was 93.3%, and specificity, 84.2%.
PMID- 9654551
TI - Diagnosis of lumbar disc herniation by three-dimensional MRI.
AB - The lumbo-sacral region has anatomical lordosis and two-dimensional magnetic
resonance imaging (2D-MRI) cannot therefore show spinal roots including the
dorsal root ganglions in one picture. This makes it difficult to present the
lateral part of spinal root lesions. We have recently described a new three
dimensional magnetic resonance imaging (3D-MRI) method which allows a
stereoscopic view of the spinal cord and spinal nerve roots. In the present
study, we evaluated three 3D-MRI techniques, rapid imaging spin echo (RISE) small
tip angle gradient echo (STAGE), and short TI inversion recovery (STIR), for
detecting disc tissue degeneration, and spinal cord and nerve root compression
for identification of nerve roots and detecting signal changes indicative of
thickening of the nerve root, and for evaluation of the extent of herniation in
30 patients with lumbar disc herniation. The RISE method was superior for
detecting signal changes in disc degeneration, (in 100% of patients) compared
with the STAGE method (in 56.1% of patients). All methods poorly identified L4
roots compared with L5 or S1 roots. The STIR method was the best for identifying
nerve roots (L4, 62.5%; L5, 87. 5%; S1, 91.7%). STAGE and STIR were useful for
detecting injuries of the nerve roots. RISE showed disc extrusion better than the
other techniques (in 64.7% of patients). The presurgical diagnosis on 3D-MRI
agreed with the pathology findings at surgery in 71.4% of STIR, 55.6% of RISE,
and 33.3% of STAGE MR images. Our results indicate that 3D-MRI is most useful for
the diagnosis of lumbar disc herniation and spinal cord and nerve root
compression. The STIR method is best for identifying abnormalities of the spinal
cord, roots, and intervertebral discs.
PMID- 9654552
TI - Possible complications of magnetic coil stimulation in living tissue: assessment
of changes in epiphyseal cartilage.
AB - To assess the influence of repeated magnetic coil stimulation (MCS) of the
peripheral nervous system on epiphyseal cartilage, we evaluated histological and
structural changes after repeated MCS applied to the knee joints of young
rabbits. There was a slight but significant histological change when repeated MCS
at 100% intensity (100% of the maximal output) exceeded 600 times per day.
However, we found no gross structural effects on the bone. We conclude that, if
these results can be extrapolated to humans, MCS should be safe for stimulating
peripheral nervous system for clinical electrophysiologic examinations in
children.
PMID- 9654553
TI - Influence of water immersion stress on peripheral nerve recovery in the rat.
AB - An experimental study was performed to investigate the relationship between
stress and peripheral nerve recovery. Male Wistar rats weighing 200-250 g were
used. The sciatic nerve was crushed unilaterally with an aneurysm clip. Stress
was applied by water immersion for 3 h, three times a week, from 1 week
preoperatively, and continued for 6 or 8 weeks. The animals' walking tracks were
measured every week to evaluate nerve function, and a sciatic functional index
(SFI) was calculated. Specimens for histological examination were taken from the
nerve at a site distal to the crush injury. By 3 weeks postoperatively, the SFI
in the non-stress groups had recovered, but it remained at significantly lower
levels in the stress groups (P < 0.01). Histological studies showed that the
recovery of nerve fibers was retarded and regenerating axons were smaller in the
stress groups. Peripheral nerve recovery after crush injury was suppressed by
water-immersion stress.
PMID- 9654554
TI - Changes in the extracellular matrix on the surface of sintered bovine bone
implanted in the femur of a rabbit: an immunohistochemical study.
AB - The interface of implanted True Bone Ceramics (TBC; sintered bovine bone; Koken,
Tokyo, Japan) was examined. In the primary experiment, TBC was implanted into the
bone marrow of a rabbit's femur. The extracellular matrices (types I, II, and III
collagens and fibronectin) of decalcified specimens collected 1-48 weeks
postoperatively were immunohistochemically examined. Undecalcified sections
collected 6 weeks postoperatively were used for line analyses of calcium and
phosphorus, by a scanning electron microscope-electron probe microanalysis (SEM
EPMA) method. In a secondary experiment, TBC was implanted into an osteochondral
defect of a femoral condyle, harvested 1-12 weeks postoperatively, and
decalcified to examine the extracellular matrices at the interface. In the bone
marrow in the early phase, TBC had absorbed quantities of fibronectin. Immature
bone (containing both types I and III collagens) in direct apposition to the
ceramic surface had matured (containing type I collagen alone) in the TBC pores.
SEM-EPMA revealed the continuity of high levels of calcium and phosphorus at the
TBC-bone interface. In the secondary experiment, enchondral ossification or
fibrous tissue formation was observed near the articular surface. However, in the
subchondral layer, direct bone formation was observed in the TBC pores. It was
concluded that TBC has excellent bioactivity for inducing maturation of new bone
matrix on porous surfaces.
PMID- 9654555
TI - Role of norepinephrine and excitatory amino acids in edema of the spinal cord
after experimental compression injury in rats.
AB - The role of norepinephrine and excitatory amino acids in edema of the spinal cord
after an acute experimental compression injury was studied in rats. Control rats
received the compression injury only. Intraspinal norepinephrine was depleted in
one rat group by injection of 6-hydroxydopamine (6-OHDA) into the subarachnoid
space to selectively destroy catecholamine neurons and in a third group MK-801
was administered intravenously to block receptors for N-methyl-d-aspartate
(NMDA), an excitatory amino acid. Recovery from motor paralysis and suppression
of edema of the spinal cord were then compared in the three groups. Significant
recovery from motor paralysis was found 12 h after injury in the 6-OHDA-treated
rats, compared with the controls, and 24 h after injury in the MK-801-treated
rats. Edema of the spinal cord was significantly suppressed for up to 24 h after
injury in the 6-OHDA-treated rats. The MK-801-treated rats showed no significant
suppression of the edema until 24 h after the spinal cord injury. It was
concluded that norepinephrine is primarily involved in the formation of vasogenic
edemas, which develop in the early stages after an injury, whereas excitatory
amino acids affect the formation of cytotoxic edemas, which develop at a
relatively later stage.
PMID- 9654556
TI - Site of origin of spinal cerebrospinal fluid pulse wave.
AB - : Since vascular pulsation in the cerebrospinal fluid causes the cerebrospinal
fluid pulse wave (CSFPW), spinal CSFPW may serve as a monitor of spinal cord
blood flow. However, there are two possible sources of spinal CSFPW: brain and
spinal cord pulsation, and it is unclear for which region spinal CSFPW provides
blood flow information. To resolve this question, we analyzed changes in CSFPW
caused by occlusion of the large vessels in mongrel dogs. The thoracic and
abdominal aorta (TA group, n = 13; AA, n = 6), bilateral internal carotid
arteries (ICA, n = 7), and superior and inferior vena cava (SVC, n = 6; IVC, n =
8) were occluded. The CSFPW was measured at the second cervical and sixth lumbar
spine level. To eliminate the influence of hemodynamic changes caused by the
occlusion, CSFPWs were decomposed into component frequencies, harmonic waves
(HWs), and analyzed using the system analysis method. After occlusion, cervical
CSFPW was decreased in groups ICA (change in the first HW, 38%; P < 0.05 by
Wilcoxon signed-ranks test), TA (40%; P < 0.05), and SVC (53%; P < 0.05), while
lumbar CSFPW was decreased in groups TA (71%; P < 0.01), AA (78%; P < 0.05), and
IVC (48%; P < 0.05). These results show that spinal CSFPW provides information on
the blood flow of a relatively localized region, and could be used to monitor
spinal cord blood flow.
PMID- 9654557
TI - Capillaries with fenestrations around regenerating muscle fibers in the soleus
muscle of the dystrophic (dy) mouse.
AB - To investigate the morphological changes in capillaries around regenerating
muscle fibers in the dystrophic (dy) mouse, we examined capillaries in the soleus
muscles of 30-day-old control and dy mice by electron microscopy. In the control
mice, the intramuscular capillaries were continuous. In the dystrophic mice, the
muscles contained degenerative muscle fibers and many small muscle fibers
regenerating after necrosis; these fibers had centrally located nuclei. The
capillaries in the dy mice were mostly continuous, but some had a narrow vascular
lumen around regenerating muscle fibers, possibly indicating newly formed
capillaries. Moreover, about 20% of the capillaries with a narrow vascular lumen
had a small number (less than five) of fenestrae bridged by a single-layered
diaphragm. These findings suggest that capillary networks around muscle fibers
regenerating after necrosis are remodeled by newly formed capillaries, and some
of these capillaries have fenestrae in the endothelium to increase the supply of
nutrients and oxygen to the regenerating muscle fibers.
PMID- 9654558
TI - Treatment of brachial plexus injury.
AB - A brachial plexus injury is the most severe nerve injury of the extremities. To
achieve good results from treatment, correct diagnosis and early nerve repair are
mandatory. The brachial plexus should be explored as early as possible if there
is an incised wound, if clinical findings or diagnostic imaging indicate that at
least one root is avulsed, if there is damage to the subclavian artery, and if
there is total-type injury. With an upper-type injury with no clinical signs of a
preganglionic lesion, the patient should be treated conservatively for 3 months
and if there are no signs of recovery, then the brachial plexus should be
explored. During this exploration, recording of the spinal cord evoked potential
(ESCP) or the somatosensory evoked potential (SEP) is mandatory to determine the
site of injury. Nerve grafting is indicated for a rupture in the root
demonstrating a positive ESCP or SEP potential, in the trunk or in the cord.
Exploration of the brachial plexus should be extended distally as far as possible
to achieve good results after nerve grafting; when this was done more than M3
(MRC grading) power of the infraspinatus, deltoid, and biceps was achieved in
more than 70% of our 32, 30, 33 patients, respectively. Results of nerve grafting
for the forearm muscles have been very poor. Intercostal nerve transfer is
recommended to restore elbow flexion in root avulsion type of injury, with elbow
flexion to more than M3 being regained in 70% of our 221 patients. The best
results of intercostal nerve transfer were achieved in patients younger than 30
years who received the operation within 6 months after injury. Motor recovery of
hand function after intercostal nerve transfer was poor but protective sensation
was restored in fingers innervated by the median nerve. The recommended treatment
for each type of injury is described according to the results achieved.
PMID- 9654559
TI - Management of tumor patients: introduction to the annual musculoskeletal tumor
meeting of the japanese orthopaedic association
PMID- 9654560
TI - Axial alignment of the lower limb in patients with isolated meniscal tear.
AB - Meniscal tears do not always result from trauma. To elucidate other factors
responsible for meniscal tears, we evaluated the axial alignment of the lower
limb in 385 patients (385 menisci) with isolated meniscal tear who were examined
between 1972 and 1994. The patients were aged 50 years or less and had no
ulceration or defect of articular cartilage of the knee when examined
arthroscopically. Of the 385 menisci, 90 were lateral complete discoid; 110,
lateral incomplete discoid; 68, lateral semilunar; and 117, medial semilunar.
Patients in each of these four groups were divided into four subgroups according
to sex and whether there was an obvious history of trauma. The so-called
Mikulicz's mechanical axis of the affected side was utilized to evaluate the
alignment. The axial alignment of the lower limb was normal in the patients with
isolated tears of lateral complete discoid meniscus, lateral incomplete discoid,
or lateral semilunar. It appeared that the axial alignment of the lower limb did
not have a relationship with the occurrence of these tears. Patients with
isolated tears of medial semilunar meniscus without obvious trauma, showed varus
deformity of the knee. This deformity appeared to be closely related to the
presence of medial meniscal tear.
PMID- 9654561
TI - Age-related changes in cortical bone in women: metacarpal bone mass measurement
study.
AB - The mechanism of age-related cortical bone loss was investigated in 229 Japanese
women, 41-94 years of age, by metacarpal bone mass measurement. While no
significant correlation was found between bone width and age, a significant
increase in bone marrow width, and significant decreases in cortical bone density
and total bone mass were observed in association with aging (P < 0.0001). There
was a significant negative correlation between total bone mass and bone marrow
width (r = -0.239; P < 0.0005), and significant positive correlations between
both total bone mass and cortical bone density (r = 0.539; P < 0.0001) and
cortical bone width (r = 0.839; P < 0.0001). The findings suggested that age
related cortical bone loss in middle-aged and elderly women resulted from two
different factors; a decrease in cortical bone density caused by progression of
intracortical porosity, and a decrease in cortical bone width as a result of bone
loss on the endosteal surface. The latter had a greater influence on an age
related cortical bone loss than the former.
PMID- 9654562
TI - Detection of human serum antibody to encapsulated strains of Staphylococcus
aureus by enzyme-linked immunosorbent assay inhibition test.
AB - A specific and rapid enzyme-linked immunosorbent assay (ELISA) inhibition test
was employed for detection of immunoglobulins to Staphylococcus aureus (S.
aureus) capsular polysaccharide in human serum. Cap-sular polysaccharide antigens
obtained from Smith diffuse (capsular type 2), Reynolds (capsular type 5), or
Becker (capsular type 8) strains of S. aureus were added to microplates coated
with these strains. Seventy-four patients with open fractures (31 serum samples
from those with staphylococcal infections, 10 serum samples from those with non
staphylococcal infections, and 33 serum samples from the non-infected group) and
28 serum samples from healthy controls were then added. The plates were incubated
at 37 degreesC for 2 h and the ELISA was performed. The ELISA inhibition assay
showed remarkable inhibition with the capsular type 2, 5, and 8 polysaccharides
in the 33 serum samples from the non-infected group and in the 28 serum samples
from the healthy controls, but low inhibition was observed with the 31 sera with
staphylococcal infections. Positive immunoglobulin (Ig)G and IgM titers showed
marked inhibition with this assay, but IgA titer were not seen in any samples.
These results indicate that the quantitation of human serum antibody against S.
aureus capsular polysaccharide by the ELISA inhibition assay is useful for the
demonstration of protective activities against S. aureus.
PMID- 9654563
TI - Morphological study of mechanoreceptors on the coracoacromial ligament.
AB - We performed gold chloride staining of coracoacromial ligaments removed at
operation, observed the peripheral nerve endings in the ligament, and studied
their distribution and changes with aging in order to clarify the proprioception
of the shoulder joint. The coracoacromial ligament was found to contain four
types of typical nerve endings: Pacinian corpuscles, Ruffini receptors, Golgi
tendon organ-like receptors, and free nerve endings. In addition, non-typical
Pacinian corpuscles and Ruffini receptors with non-typical morphology were
present. There were also unclassifiable nerve endings with a morphology which did
not fit any of the above categories. These typical, non-typical, and
unclassifiable nerve endings were all widely distributed on the surface of the
subacromial side at the insertion into the acromion and around the coracoid
process in the ligament. Free nerve endings were found sporadically on the
surface of the subacromial bursal side in the ligament. The resected
coracoacromial ligaments (23 specimens) were divided into two groups based on the
disorder that required surgery: a fracture group without subacromial impingement
(5 specimens) and a group with subacromial impingement (18 specimens). Age
related changes in the number of nerve endings were compared in each group. The
total number of nerve endings decreased with age in both groups. The number of
Pacinian corpuscles, Ruffini receptors, Golgi tendon organ-like receptors, and
free nerve endings of typical morphology tended to decrease with age. The data
from the fracture and subacromial impingement groups were not analyzed
statistically because of the difference in the number of specimens in each group.
However, the total number of nerve endings was lower in the subacromial
impingement group than in the fracture group at all ages. The typical nerve
endings of the coracoacromial ligament in both groups tended to decrease in the
elderly, suggesting that the proprioception of the shoulder joint may become
impaired with aging.
PMID- 9654564
TI - Role of patellar tendon on the population of muscle fiber types and the
contractile properties of single glycerinated muscle fibers in quadriceps muscles
of rats.
AB - The role of the patellar tendon (PT) in the contractile properties of quadriceps
muscle was investigated. After PT resection (partial or complete), PT
reconstruction, or a sham operation, rats were forced to run on a rodent
treadmill. The histochemical and mechanical characteristics of the vastus
medialis (VM) and vastus lateralis (VL) muscles were examined 2, 4, and 8 weeks
after treatment. There were no significant changes in either fiber type
population or the contractile properties of glycerinated single muscle fibers
from VM and VL 2 and 4 weeks after partial PT resection. Complete PT resection
caused a decrease in the population of type I fibers in VM, while the running
training after PT reconstruction increased the population of type I fibers in VM.
For both the PT resection and PT reconstruction groups, the Hill coefficient, an
indicator of the Ca2+ sensitivity of myofilaments, was calculated from the pCa
tension relationship of glycerinated single muscle fibers. In the PT
reconstruction group, the Hill values for fibers isolated from VM were
significantly decreased by running training, but the Hill values for VL were not.
The effect of running training on the Ca2+ sensitivity of myofilaments in muscle
fibers with PT reconstruction was different from that in muscle fibers without PT
treatment. Both resection and partial resection of the PT in this animal model
had heterogeneous effects on the contractile properties of quadriceps muscles; we
presume that, clinically, we must give careful consideration to PT treatment.
PMID- 9654565
TI - Tuberculous bursitis of the greater trochanter.
AB - A patient with tuberculous bursitis of the greater trochanter is reported. A 37
year-old woman had experienced persistent dull hip pain and noticed diffuse
swelling over the greater trochanteric region. Plain radiograph revealed
unremarkable osteopenic changes in the greater trochanter and faint
mineralization in the vicinity of the trochanter. Computed tomogram showed
erosion of the trochanter and a large soft tissue mass. Magnetic resonance
imaging demonstrated a large multicystic mass. Histology of the cyst wall,
showing chronic granulomatous tissue, and a positive culture of Mycobacterium
tuberculosis confirmed the diagnosis of musculoskeletal tuberculosis. Complete
excision of the lesion, followed by 6 months of antituberculous chemotherapy with
rifampicin and isoniazid, cured the disease. There has been no sign of recurrent
disease in 30 months of follow-up. Correct diagnosis was difficult because of its
rarity, but modern imaging technology, magnetic resonance imaging, in particular,
was extremely useful for showing the extent of the disease. Tuberculous infection
should be considered as a differential diagnosis in patients with persistent hip
pain.
PMID- 9654566
TI - Normalization of the coronal and sagittal profile in idiopathic scoliosis:
options of treatment.
AB - There are many current strategies for normalizing coronal and sagittal profile in
the idiopathic adolescent and adult scoliosis patient. Anterior and posterior
approaches have their advantages and limitations. Many factors have to be
considered in determining the "best" approach, as idiopathic scoliosis presents
with a wide diversity of deformity and curve pattern. Those points are reviewed
in this manuscript.
PMID- 9654567
TI - Nasogastric and nasoenteric feeding tubes.
AB - This article discusses the placement of nasogastric and nasoenteric feeding tubes
using blind, pH, magnetic, sonagraphic, electromyogram, fluoroscopic, and
endoscopic-assisted techniques. Bedside tests to ensure appropriate tube location
are detailed. The complications of inappropriately-located tubes are listed, and
methods to reduce adverse side effects are given.
PMID- 9654568
TI - Percutaneous endoscopic gastrostomy.
AB - Accessing the stomach via a gastrostomy is the preferred method for providing
enteral nutritional support when supplementation is required for more than three
or four weeks. Since its introduction in the early 1980s, percutaneous endoscopic
gastrostomy has become the most popular method for creating a gastrostomy. It is
a quick and cost-effective method and has supplanted open gastrostomy for the
establishment of a gastrocutaneous fistula to provide access to the stomach for
numerous indications. It is associated, however, with serious and potentially
lethal complications which must be completely understood by the endoscopist. In
addition, patient selection and thorough attention to details are paramount to
the performance of a safe percutaneous endoscopic gastrostomy.
PMID- 9654569
TI - Direct percutaneous endoscopic jejunostomy.
AB - Jejunal feeding often is preferable to gastric feeding, particularly in the
following situations: high risk for aspiration; gastric resection (partial or
total); gastric pull-up; gastric outlet obstruction; obstructed or nonfunctioning
gastrojejunostomy; and gastric dysmotility. The technique of placing a thin tube
through a gastrostomy tube and pulling it endoscopically into the proximal
jejunum allows delivery of nutrients into the jejunum. The results of this
technique, however, have been poor. The direct percutaneous endoscopic
jejunostomy technique allows placement of tubes directly in the jejunum with a
success rate of around 85% and a minimal complication rate which is comparable to
that of PEGs.
PMID- 9654570
TI - Surgical and laparoscopic techniques for feeding tube placement.
AB - Surgeons have at their disposal multiple options for providing enteral access in
a myriad of circumstances. This article reviews the techniques for surgical
placement of enteral access as well as the indications, benefits, and
complications for each procedure. The feeding tubes commonly available are
described, and considerations involved in the choice of procedure are discussed.
PMID- 9654571
TI - Enteral feeding solutions.
AB - There has been a widespread proliferation of enteral feeding solutions for
general and specific therapeutic use. This article reviews the nutrient
substrates and physical characteristics of these solutions with consideration to
both psychological and clinically-proven principles pertinent to their
application. The rationale for the composition and efficacy studies of disease
specific solutions also is presented.
PMID- 9654572
TI - Design and production of enteral feeding tubes.
AB - The evolution of enteral feeding via tubes, syringes, and other mechanical
devices probably began in Egypt before the birth of Christ. Today's feeding tubes
are a safe and effective means for providing long-term feeding to patients unable
to maintain sufficient nutrition by oral intake. The needs of enterally-fed
patients are presently being met with feeding tubes that are biocompatible, easy
to use, and relatively inexpensive to manufacture.
PMID- 9654573
TI - Enteral feeding in critical care, gastrointestinal diseases, and cancer.
AB - This article discusses the many advantages and changes that have occurred in the
nutritional management of critically-ill patients, patients with gastrointestinal
diseases, and patients with selected cancers. Mechanical obstruction is the only
absolute contraindication to enteral nutrition. This article reviews the present
aggressive approach to the use of enteral nutrition.
PMID- 9654574
TI - Enteral nutritional support in burn patients.
AB - Early and continued nutritional support has been determined to be an important
component of therapy for seriously burned patients. The hypermetabolic response
to severe injury requires increased calorie and protein intake to blunt the
catabolism and loss of lean muscle mass. Enteral feeding has been found to
directly nourish the gastrointestinal tract and may help reverse the defective
gut barrier which accompanies burn shock. In contrast, intravenous nutritional
support appears to lack effectiveness in burn patients and may actually increase
morbidity and mortality.
PMID- 9654575
TI - Enteral nutrition in the pediatric population.
AB - Enteral feeding, the provision of liquid nutrients into the gastrointestinal
tract, is an important component of pediatric care. For the infant or child with
a functioning or even a partially-functioning GI tract, the use of the enteral
route provides a safe and efficient means of delivering nutrition at a time of
life when requirements are extremely high. In addition to high nutrient
requirements in the early years of life, there are a number of specific pediatric
conditions, such as failure to thrive, short bowel syndrome, and congenital heart
disease, which place further demands on the growing child. These demands can be
met through the careful use of enteral feeds. This article reviews the physiology
and practical application of enteral feeding to the pediatric age group.
PMID- 9654576
TI - Outcome of long-term enteral feeding.
AB - In the past two decades, many technical advances have made tube enteral feeding
much more comfortable and acceptable to patients and their families. This has
greatly expanded the use of this therapy, both in clinical conditions where it
was traditionally prescribed and in many other diagnoses. This expanded use
raises important questions about how much enteral nutrition is being used, the
medical outcome in different clinical conditions, and the quality of life
experienced by long-term therapy users. This article addresses these outcome
issues for patients in the nonhospital setting.
PMID- 9654577
TI - Ethical issues in instituting and discontinuing enteral feeding.
AB - The shift from inpatient care has not lessened the importance of ethical issues
in caring for patients. Dilemmas involving withholding and withdrawing enteral
nutrition require input from the patient, family, and caregivers. Decisions to
forego or discontinue treatment such as home enteral support should never be
distinguished from the responsibility of providing support and compassionate care
throughout life, even during dying.
PMID- 9654578
TI - Cost and cost-benefit of enteral nutrition.
AB - Enteral nutrition is a therapy provided routinely in the hospital, extended care,
and home care settings for patients who are unable to maintain adequate oral
nutrition yet have a functioning gastrointestinal tract. Information about the
cost and effectiveness or benefits of enteral nutrition in the hospital and home
care settings is important to know when making decisions about providing this
therapy. This article discusses the methods used in cost analysis, explains the
difference between cost and charges, and reviews the current information known
about the cost-effectiveness and cost-benefits of enteral nutrition in the acute
care setting and at home.
PMID- 9654579
TI - Techniques, coils, pulse sequences, and contrast enhancement in pediatric
musculoskeletal MR imaging.
AB - The first half of this article emphasizes the basic techniques involved in
performing MR imaging of the pediatric musculoskeletal system. These include
patient preparation, sedation issues, immobilization, coil selection, and pulse
sequences. The second half of this article provides a detailed discussion of the
use of Gadolinium and its enhancement characteristics in the normal developing
musculoskeletal system, and its pathologic states are given.
PMID- 9654580
TI - Growth cartilage: normal appearance, variants and abnormalities.
AB - The cartilaginous structures in the growing ends of the bone have a complex
anatomy. MR imaging allows exquisite depiction of these structures. The normal
anatomy and biochemical features of the zones of cartilage are reviewed. Based on
an analysis of signal characteristics, it is possible to optimize the use of
pulse sequences to study the normal structures and abnormalities of growing bone.
PMID- 9654581
TI - Normal bone marrow: signal characteristics and fatty conversion.
AB - Understanding the dynamic MR appearance of normal bone marrow during childhood is
essential. This article reviews normal bone marrow structure and development,
especially the process of fatty conversion, laying the cornerstone for accurate
interpretation of marrow MR imaging.
PMID- 9654582
TI - Congenital anomalies and vascular birthmarks of the lower extremities.
AB - MR imaging is an invaluable tool for the evaluation of congenital abnormalities
and vascular birthmarks of the extremities in children. These abnormalities of
the immature musculoskeletal system are often underestimated by radiography. MR
imaging is useful for diagnosis, assisting in therapy, showing response to
treatment, and determining prognosis. Localized and generalized abnormalities of
the lower extremities and issues pertinent to their MR imaging are illustrated in
this article.
PMID- 9654583
TI - Musculoskeletal trauma in children.
AB - MR imaging has facilitated the study of pediatric injuries by demonstrating the
extraosseous and cartilaginous component of these lesions. In injuries to the
epiphysis and physis, osteochondral injuries and avulsion injuries, the
cartilaginous component is usually the most important part of the lesion. Stress
fractures and other injuries to the marrow also can be demonstrated with MR
imaging. In the context of musculoskeletal injuries in children, MR imaging is
most valuable in demonstrating the extent of injuries to radiographically occult
areas.
PMID- 9654584
TI - MR imaging of pediatric musculoskeletal inflammatory and infectious disorders.
AB - Inflammatory and infectious disorders of the skeletally immature extraspinal
musculoskeletal system affect the bones, contiguous soft tissues, muscles, and
joints. MR imaging of osteomyelitis, soft tissue infection, inflammatory muscle
disease, and acute and chronic joint disease are discussed in the context of
underlying pathophysiology. Discussion includes imaging optimization,
contribution of MR imaging to overall patient management, and differential
diagnostic considerations for the pediatric patient.
PMID- 9654585
TI - Differential diagnosis of pediatric musculoskeletal masses.
AB - MR imaging plays a major role in the evaluation of children with soft tissue and
bone tumors. While the imaging characteristics of these lesions are often
nonspecific, MR imaging provides valuable information on the extent of disease
and relationship of tumors to the neurovascular bundle and other vital
structures. This article reviews the radiographic and MR imaging appearances and
clinical presentations of a wide range of musculoskeletal masses that occur in
children.
PMID- 9654586
TI - Advances in MR imaging of pediatric musculoskeletal neoplasms.
AB - MR imaging has evolved as the most important diagnostic test for local staging of
primary bone and soft tissue tumors, for monitoring response to chemotherapy, and
for detecting postoperative tumor recurrence. MR imaging provides accurate
preoperative staging of local tumor extent and helps to obtain adequate safety
margins, prerequisites for successful limb-salvage surgery. Postcontrast MR
imaging studies are helpful for evaluating the presence or absence of tumor
necrosis during chemotherapy. Dynamic MR imaging after intravenous bolus
administration of Gd-DTPA or other paramagnetic contrast media is particularly
useful for assessing response to chemotherapy. Diffusion-weighted MR imaging is a
new technique that is potentially capable of detecting and quantitating the
amount of tumor necrosis after chemotherapy or radiation therapy.
PMID- 9654587
TI - Diffuse marrow disorders in children.
AB - This article describes MR imaging findings in neoplastic processes affecting the
marrow of children. Differentiation from non-neoplastic processes, such as edema
and hematopoietic marrow is described.
PMID- 9654588
TI - Disorders of the Hip.
AB - MR imaging has fulfilled many of the dreams of the pediatric radiologist studying
the hip: it has allowed depiction of detailed anatomy, evaluation of vascularity
and perfusion, determination of synovial proliferation activity in chronic
arthritis, and detection of bone marrow changes with great sensitivity. MR
imaging also has brought some disenchantments; it lacks specificity, it is
expensive and long, and it often requires sedation. MR imaging is operator
dependent and hardware and software dependent. Finally, issues of cost
effectiveness and clinical efficacy in comparison with good physical examination
and conventional radiography or ultrasound remain unresolved. Demonstration of
its cost-effectiveness in the clinical setting is clearly the dominant challenge
facing MR imaging today.
PMID- 9654589
TI - The pediatric knee.
AB - MR imaging has become an indispensable tool in the evaluation of knee disorders.
It is now widely relied on by clinicians, especially orthopedic surgeons, for
guiding arthroscopic procedures and for staging tumor prior to resection. MR
imaging has proved so successful that it has largely replaced arthrography in the
evaluation of knee problems.
PMID- 9654590
TI - The pediatric foot and ankle.
AB - MR imaging can be extremely helpful in evaluating congenital and acquired
deformities of the foot and ankle. Knowledge of the normal developmental anatomy
of the foot and ankle is important to accurately identify abnormalities versus
normal variants. The foot and ankle may be abnormal because of trauma, infection,
tumor, or systemic disease. MR imaging can help in the differential diagnosis of
abnormalities as well as in treatment planning and follow-up.
PMID- 9654591
TI - Disorders of the upper extremity in children.
AB - This article presents a brief overview of the indications of MR imaging in a
variety of disorders of the upper extremity of the pediatric patient. This covers
congenital anomalies: Sprengel shoulder, Poland sequence, arthrogryposis;
posttraumatic lesions of cartilage, bone, tendon, muscle and nerve including the
brachial plexus injury; inflammatory arthritis and synovitis; bone and joint
infection; osteochondritis dissecans, bone necrosis and infarcts in sickle cell
anemia and juvenile Gaucher disease, as well as tumors. In this last category,
the authors briefly describe the appearances of cysts and tumors of bones and
soft tissues of the upper extremity. Indications for the intravenous
administration of Gadolinium are given throughout the article with emphasis on
the synovial enhancement seen in active arthritis and synovitis.
PMID- 9654592
TI - Chemotherapy of oesophago-gastric cancer.
AB - Oesophageal and gastric cancers are common tumors that represent a number of
challenges for oncologists, gastroenterologists and surgeons. The prognosis
remains poor with the majority of patients presenting with advanced disease.
Combined chemotherapy and radiotherapy has demonstrated a survival benefit in
patients with loco-regional oesophageal cancer compared to radiotherapy alone. In
an interim analysis we have observed a 62% response rate using a chemoradiation
regimen based on protracted venous infusion of 5-fluorouracil and cisplatin
combined with radiotherapy in patients with inoperable oesophageal cancer.
Improved outcomes with loco-regional disease has rekindled interest in
preoperative therapy. In a trial comparing preoperative chemoradiation to surgery
alone in patients with operable oesophageal adenocarcinoma, survival was improved
with multimodality treatment. In addition, a study including both adeno- and
squamous carcinomas demonstrated a trend towards improved survival. A complete
pathological response to chemoradiation was associated with significantly
improved survival. Gastric cancer is one of the most chemosensitive solid tumors
of the gastrointestinal tract with the majority of patients being suitable for
palliative chemotherapy. The ECF (epirubicin, cisplatin, protracted venous
infusion 5-fluorouracil) regimen was developed in the Gastrointestinal unit of
the Royal Marsden Hospital and first reported in 1991. In a prospective
randomised trial including 274 patients ECF has been compared with the standard
combination of 5-fluorouracil, adriamycin and methotrexate (FAMTX) in patients
with previously untreated gastric cancer. Overall response rate, failure-free and
overall survival were significantly improved with ECE, ECF also demonstrated
improved quality of life and cost effectiveness when compared to the FAMTX
regimen. ECF should now be regarded as the standard treatment for advanced
oesophago-gastric cancer against which new therapies should be compared. In
addition the Medical Research Council are conducting a trial randomising patients
between surgery alone and perioperative chemotherapy using the ECF regimen in
operable gastric cancer.
PMID- 9654593
TI - Drug resistance in ovarian cancer - the role of p53.
AB - The aims were to determine the importance of p53 and bcl-2 expression on the
response to chemotherapy with alkylating agents in patients with ovarian cancer.
We have followed the response to chemotherapy in a series of 59 patients with
ovarian adenocarcinoma designated as p53 and bcl-2 positive or negative by
immunocytochemistry. Of these cases, 50 received either cisplatin + treosulfan or
treosulfan alone. Immunocytochemistry for p53 was positive in 28/59 tumors.
Patients were grouped according to their response to chemotherapy (stable or
progressive disease) assessed at 6, 12, and 18 months. There was increasing
divergence of p53+ and p53- tumors over time. Of those which were p53+, 25%
showed progression at 6 months, 80% at 12 months and 89% progression at 18
months. In contrast, 23%, 50%, and 67% of p53- tumors showed progression at 6, 12
and 18 months respectively. For bcl-2, in 23/55 positive tumors there was
progression in 35%, 78% and 94% compared with 25%, 57% and 59% in bcl-2 negative
tumors at 6,12 and 18 months respectively. Those tumors which were bcl-2 and p53
negative were most likely to progress, while those which were bcl-2 and p53
positive had the best prognosis. These differences did not translate into
increased overall survival with minimum follow-up of 12 months. This data lends
support to our suggestion that despite initially increased susceptibility to
alkylating agents, enhanced genomic instability due to p53 inactivation may
render tumors more likely to develop resistance to chemotherapy over time. This
effect may be altered by bcl-2 function, lack of which will lead to a good
response to chemotherapy as the tumor's ability to undergo apoptosis will not be
compromised.
PMID- 9654594
TI - Cathepsin D immunoreactivity in ovarian cancer: correlation with prognostic
factors.
AB - In view of the somewhat inconclusive nature of the reports of the role of
Cathepsin D (Cath D) in ovarian carcinoma and its relationship with various other
parameters of malignancy the present study was performed to aid in the further
clarification of this role. One hundred freshly resected primary ovarian
carcinomas of various histological types were studied for ER, PR and Cath D
status and the results examined with respect to menopausal status, histology,
size and lymph node invasion. In our series Cath D positivity was more frequent
in serous than in other types of ovarian cancer but this Cath D positivity was
not related to the frequency of lymph node invasion regardless of the size of the
tumor. Nor was any association observed between Cath D positivity and ER or PR
status of the tumors or the menopausal state of the patients. The reported
prognostic value of Cath D, ER and PR is discussed as well as the distinction
between tumor invasion by lymphatic channels and direct interstitial
infiltration. It was concluded that Cath D may not play a role in the former mode
but, as might be expected from its proteolytic properties, in local spread by
means of tissue destruction.
PMID- 9654595
TI - Cytokine sensitivity of metastatic human melanoma cell lines-- simultaneous
inhibition of proliferation and enhancement of gelatinase activity.
AB - The effect of a panel of cytokines on the proliferation and type IV collagenase
production was studied in four melanoma cell lines of different origin,
tumorigenicity and metastatic capacity. TGF-b, TNF-a and to a lesser extent, IL
1a exhibited antiproliferative effect on the cell lines, with some lines showing
varying degree of resistance. The sensitivity did not correlate directly with the
origin or the biological behavior of the tumor lines, suggesting that cytokine
resistance of advanced stage melanoma cells may be relative. IL-2, IL-10 and IL
12 displayed little or no effect on proliferation. The effect of cytokines on
metalloproteinase production showed a cell line dependent pattern. Interestingly,
those cytokines that exhibited the most pronounced antiproliferative activity,
also proved most effective in stimulating collagenase secretion, often
simultaneously, in the same line. The results indicate that pleiotropic cytokines
can have positive and negative effects simultaneously on various steps of tumor
progression.
PMID- 9654596
TI - Role for glucose transporter 1 protein in human breast cancer.
AB - Glycolysis is increased in cancer cells compared with normal cells. It has been
shown that glucose enters cells via a family of five functional glucose
transporters (GLUT). However, GLUT expression appears to be altered in human
breast cancer, which may serve as a selective advantage and facilitate the
metastatic potential of these cells. The relationship of GLUT isoform expression
and breast cancer cell invasiveness has not been adequately addressed. Thus, the
purpose of this study was to investigate whether an association exists between
GLUT expression and human breast cancer cell invasiveness. Invasiveness of the
human breast cancer lines MCF-7, MDA-MB-435 and MDA-MB-231 was measured using an
in vitro assay and compared with cellular GLUT isoform expression, assessed by
Western blot analysis and verified by immunohistochemistry in a poorly
differentiated human ductal breast cancer. Cell surface GLUT-1 expression was
associated with the invasive ability of MCF-7 (2.0 + 0.02%), MDA-MB-435 (6.4 +/-
0.4%), and MDA-MB-231 (19.3 +/- 2.0%). However, GLUT-2 and GLUT-5 were inversely
associated with invasiveness; GLUT-3 expression was variable; and GLUT-4 was
undetected. In a poorly differentiated human ductal breast cancer, in situ GLUT-1
staining was intense. GLUT-1 expression was associated with the in vitro invasive
ability of human breast cancer cells which was validated in situ. If this
relationship is found to exist in a larger number of human breast cancer tissues,
it may be possible to develop diagnostic and therapeutic strategies based on
targeted GLUT isoform expression.
PMID- 9654597
TI - Histidine decarboxylase in peripheral lymphocytes of healthy individuals and
chronic lymphoid leukemia patients.
AB - Histidine decarboxylase (HDC), the only enzyme capable of synthetizing histamine,
has been found in many proliferating cells and tissues suggesting a role of
histamine in cellular proliferation. In this study expression of HDC and the
significance of histamine in the proliferation of peripheral lymphocytes of five
healthy persons and six patients with chronic lymphoid leukemia (CLL) was
examined. Expression of HDC mRNA and the protein was proved by reverse
transcriptase polymerase chain reaction and by immunoblot, respectively. The role
of histamine was studied in proliferation assays in the presence of irreversible
inhibitor of the HDC (alpha-fluoromethylhistidine--aFMH) and also by competing
for the intracellular binding sites of histamine using N,N-diethyl-2, 4
phenylmethyl-phenoxy-ethanamine-HCl (DPPE). By inhibiting the HDC enzyme activity
by FMH and blocking the intracellular action of histamine by DPPE, a significant
decrease in cell proliferation was observed in mitogen stimulated lymphocytes of
healthy donors. In CLL patients the proliferation of leukemic lymphocytes was
significantly inhibited by blocking the binding of histamine to intracellular
binding sites by DPPE but not by FMH inhibiting only the de novo histamine
formation. The observations suggest that HDC has functional relevance in
lymphocytes, since mitogen induced lymphocyte proliferation of healthy donors is
mainly enhanced by de novo synthesis and subsequent action of intracellular
histamine. Alternatively, in constitutively proliferating chronic lymphoid
leukemia cells we suggest that the preformed pool but not the de novo synthesized
intracellular histamine interferes with cellular proliferation.
PMID- 9654598
TI - Lower cancer risk in medium high radon.
AB - Radon exposure was shown to be carcinogenic and suggested as a possible causative
factor for lung cancer in man. A hypothesis is introduced that medium high radon
(between 110 and 165 Bq/m3) causes lower cancer risk among women younger than 61
years, independent of the type of cancer. The presented results verify this
statement with a probability of not less than 98%.
PMID- 9654599
TI - Proliferative epithelial changes in ectopic gastric mucosa of Meckel's
diverticula.
AB - Twenty-one Meckel's diverticula containing an adequate amount of assessable
heterotopic gastric mucosa were investigated for epithelial changes. Marked or
moderate foveolar hyperplasia was present in 52% and 29% of the cases,
respectively. Four cases displayed an excessive epithelial proliferation
indefinite for dysplasia. It is pointed out that reflux type gastritis or
gastropathy, which is the most common lesion in the ectopic gastric mucosa of
Meckel's diverticulum, can be associated with the same confusing epithelial
proliferation as reflux gastritis in the stomach, but these lesions are best
regarded as representing atypia of repair. Distinguishing features from dysplasia
are maturation towards the surface, lack of hyperchromatism and abscence of
atypical mitoses. Negative p53 immunostaining and localization of the Ki-67
positivity to the expanded neck region could be additive clues that can help to
classify lesions indefinite for dysplasia as negative for dysplasia. On the basis
of the similarities of the ectopic and ortotopic gastric mucosa, it is suggested
that these additive clues previously used in other parts of the digestive tract
could also apply for the stomach.
PMID- 9654600
TI - Actin cleavage in various tumor cells is not a critical requirement for executing
apoptosis.
AB - Actin is a major cytoskeletal protein which is involved in many physiological
cellular functions such as motility, cell shape, and adhesion. Recently, actin
has also been reported to be cleaved by apoptotic proteases (i.e., caspases) and
this cleavage is thought to contribute to the apoptotic process. However,
conflicting data also exists as to whether actin represents a true caspase
substrate during apoptosis induction in vivo (i.e., inside the cells). In this
study, we critically examined the actin cleavage patterns during apoptosis of
several tumor cell lines derived from three different species (i.e., mouse, rat,
and human). Our findings demonstrate that: 1) actin cleavage in vivo is not a
common phenomenon since apoptosis caused by multiple inducers in most cell types
examined occurs without evidence of actin degradation; and 2) in certain cell
types (e.g., U937), spontaneous, actin cleavage is observed which is not
prevented by various specific chemical/peptide inhibitors of proteases such as
caspases or serine proteases although apoptosis per se is retarded by some of
these inhibitors. Our results conclude that actin is not a critical substrate for
apoptotic proteases in vivo during apoptosis.
PMID- 9654601
TI - Coccidioidomycosis in Hungary. The first import case.
AB - A case of an isolated subcutaneous coccidioidomycosis in a 61-year-old man is
presented. The patient has lived and worked in Arizona for 3 years previously but
developed no apparent clinical signs of the disease. The painless, cavitating,
tumor-like mass was surgically excised and the diagnosis was established by
histological demonstration of the fungi and confirmed by serum
counterimmunoelectrophoresis. This represents the first imported case of
coccidioidomycosis in Hungary.
PMID- 9654602
TI - Recent advances in molecular genetics of cardiovascular disorders. Implications
for atherosclerosis and diseases of cellular lipid metabolism.
AB - Two developments in molecular genetics will profoundly influence our
understanding and the diagnosis of cardiovascular disorders. First, the
identification of genes responsible for monogenic and polygenic traits by
analysis of e.g. large pedigrees and affected sib pairs provides invaluable data
regarding the role of specific genes in common diseases like arteriosclerosis,
hypertension, diabetes, thrombosis/hemostasis and obesity. Besides the insights
into the underlying pathophysiology, this knowledge will permit to identify
persons at high risk for disease development. These patients can then obtain a
targeted intervention. The second development is related to the availability of
new analytical tools for molecular biology. New methods such as sequencing by
hybridisation (SBH), DNA-array technology or matrix assisted laser
desorption/ionisation-time of flight mass spectroscopy (MALDI-TOF) permit
sequence analysis of complete genes within hours. Automated PCR-technologies with
homogenous amplicon detection formats simplify PCR and permit its use in the
routine laboratory setting. Considering cardiovascular diseases there is a number
of genes involved in lipid metabolism (apolipoproteins, lipoprotein receptors,
lipolytic enzymes), thrombosis/hemostasis (platelet receptors, pro- and
anticoagulant proteins, fibrinogen, PAI's), hypertension (angiotensin converting
enzyme, angiotensinogen) glucose metabolism (glucose transporters, enzymes) and
obesity (hormones, receptors), that are interesting candidates for sophisticated
genetic risk assessment. Furthermore, there are also gene candidates involved in
processes of early atherogenesis and chronic inflammation such as complement
proteins, cell adhesion molecules, and cellular receptors and enzymes. Most of
these gene candidates were derived from pathophysiologic knowledge and subsequent
epidemiological studies. However, it is foreseeable that in the coming years
genes will be identified which were not known so far to be involved in
cardiovascular diseases. Genetic studies will be of prime importance in this
area, as is exemplified by animal models. In the long term, analysis of these
candidate genes before the implementation of therapy will permit a targeted
intervention approach towards high risk patients. This will reduce the overall
costs of health care without reducing the quality.
PMID- 9654603
TI - Endothelial dysfunction in preeclampsia.
AB - Several years ago the hypothesis was advanced that alterations of endothelial
function could explain much of the pathophysiology of preeclampsia. Since that
time, extensive data have been generated to support the hypothesis. Markers of
endothelial activation can be demonstrated in women with overt preeclampsia. More
importantly, many of these markers precede clinically evident disease and
disappear with resolution of the disease. The original postulate was that
materials produced by the poorly perfused placenta, which is characteristic of
preeclampsia, entered the systemic circulation and altered endothelial cell
activity. This was proposed to change vascular sensitivity to circulating
pressors, activate coagulation, and reduce vascular integrity resulting in the
pathophysiological changes of preeclampsia. As data have accumulated it has
become increasingly evident that the insult to the endothelium is neither
toxicity nor nonspecific injury but rather can better be characterized as
endothelial activation. Candidate molecules have been suggested but not
established. It seems likely that the responsible agent(s) will not be unique
molecules but rather usual molecules present in excessive amounts. The hypothesis
has been expanded to invoke involvement of the maternal constitution in the
generation of endothelial injury and injurants. This concept is stimulated by the
observation that reduced placental perfusion per se is not sufficient to generate
the maternal syndrome. Women with growth-restricted fetuses frequently are not
preeclamptic. Placental bed biopsies from not only growth-restricted but also
prematurely born infants demonstrate failure of the physiological remodeling of
decidual vessels responsible for the reduced placental perfusion of preeclampsia.
This has led to the concept that preeclampsia is secondary to an interaction of
reduced placental perfusion and maternal factors. Interestingly these maternal
factors, obesity, insulin resistance, black race, hypertension, and elevated
plasma homocysteine concentration are all risk factors for atherosclerosis in
later life.
PMID- 9654604
TI - Circulating factors as markers and mediators of endothelial cell dysfunction in
preeclampsia.
AB - During the past decade a new hypothesis has been formulated that explains many of
the disparate findings associated with the pregnancy syndrome preeclampsia. With
an increased awareness of the physiological significance of vascular endothelial
cell function, the seemingly unrelated signs of hypertension, proteinuria, edema,
and hypercoagulability have converged to provide clinical evidence of a unifying
pathophysiological mechanism: systemic, maternal endothelial cell dysfunction.
Investigators have attempted to test this hypothesis through two approaches. The
first approach involves the identification of in vivo markers of vascular
endothelial cell injury in women with clinically evident preeclampsia. The second
approach focuses on the ability of circulating factors derived from the serum or
plasma of patients afflicted with preeclampsia to perturb endothelial cell
function in vitro. In this review we summarize the increasingly compelling
evidence that maternal vascular endothelial cells are a critical target for toxic
humoral activities that precipitate the multifaceted preeclampsia syndrome.
PMID- 9654605
TI - Plasma lipids and vascular dysfunction in preeclampsia.
AB - The dominating hypothesis of the preeclampsia syndrome (PES) is that placentally
derived factors are released to the maternal circulation. These factors are
believed to alter endothelial properties resulting in disturbed vasomotor
function, increased endothelial permeability, and activation of thrombogenic
factors. However, the impact of placentally derived factors on the endothelial
cells is influenced by another major variable: the "sensitivity" of the maternal
endothelium to the placental factors. Several maternal factors may play a role in
determining this sensitivity. They include chronic hypertension, diabetes, and
hyperlipidemia. In this article we discuss the possible role of hyperlipidemia
(especially high free fatty acids and hypertriglyceridemia) in the pathogenesis
of preeclampsia, viewed from this perspective. Pregnancy in general, preeclamptic
pregnancy in particular, is associated with a marked hyperlipidemia. We suggest a
parallel to atherosclerotic diseases, wherein hyperlipidemia induces endothelial
dysfunction, probably by promoting oxidative stress in the arterial wall. The
hyperlipidemia of pregnancy may have a similar effect on the endothelial cells.
When placentally derived endothelial disturbing factors, like lipid peroxides and
trophoblastic components, are released into the maternal circulation, their
effects on the endothelium may be enhanced because of hyperlipidemia-mediated
activation or "sensitization" of the endothelial cells. Alternatively,
placentally derived factors like peroxides may combine with lipoproteins, forming
complexes that are more disturbing to cells than the placental factors or
lipoproteins are individually. We also discuss the possible role of maternal
hyperlipidemia in aggravating placental insufficiency caused by poorly
transformed spiral arteries. The hemodynamic flow pattern may be markedly
different in completely and incompletely transformed spiral arteries. By analogy
to the fundamental role of hemodynamic factors in development of atherosclerosis,
we pose the hypothesis that abnormally transformed spiral arteries have an
"atherogenic" blood flow pattern that promotes lipid deposition and "acute
atherosis".
PMID- 9654606
TI - Insulin resistance syndrome in preeclampsia.
AB - Because changes in lipids, lipoprotein, and other metabolic processes, such as
hyperinsulinemia and hyperuricemia, found in preeclampsia resemble the main
features of the insulin resistance syndrome, it has been proposed that insulin
resistance may be the common denominator for such metabolic changes. Several
groups, using euglycemic-hyperinsulinemic clamping or intravenous glucose
tolerance tests (Bergman's minimal model technique), have demonstrated insulin
resistance during late pregnancy. Women with preeclampsia had higher fasting
insulin levels, but also exaggerated hyperinsulinemia, in response to an oral
glucose tolerance test, which is consistent with increased insulin resistance in
preeclampsia. No direct measurement of insulin sensitivity (clamp or minimal
model) has as yet been performed during preeclampsia. Increased insulin
resistance can activate the sympathetic nervous system and lead to an increase in
expression of receptors for endothelin, both of which events lead to increased
blood pressure. Hyperinsulinemia can also induce hypertriglyceridemia, leading to
endothelial dysfunction and reduction of prostacyclin production. This
hyperinsulinemia can persist for as long as 17 years after preeclamptic pregnancy
and may contribute to a woman's increased risk of cardiovascular disease. Insulin
resistance may not be the cause of preeclampsia, but is one of the pathogenic
factors, especially in genetically predisposed women.
PMID- 9654607
TI - Antioxidants and inflammatory cell response in preeclampsia.
AB - There is widespread evidence of inflammatory cell and antioxidant activity in
preeclampsia. However, it is difficult to disentangle the pathological changes
from the normal physiological responses to the pathological process. The site at
which the measurements are taken, and the severity of disease, alter the results.
The interaction between the mother and the fetus needs to be considered
separately, especially when the genetics of preeclampsia is considered. It is
clear that within the placenta, there is an increase in tumor necrosis factor
alpha (TNF-alpha) and lipid peroxide production. These changes are associated
with a reduction in the various placental antioxidants. This suggests there may
be a failure of the normal fetal protection systems. Lipid peroxidation is also
increased in the peripheral blood, as well as IL-6, IL-8, and TNF-alpha, which
are of monocytic origin. Stimulated monocytes produce free radicals, which can
cause oxidative damage. Maternal cells protect themselves with both plasma and
intracellular antioxidants. There is an imbalance between oxidant and antioxidant
activity in preeclampsia. Changes in membrane oxidation can lead to changes in
the membrane stability. Genetic difference in the production of TNF-alpha and
nitric oxide may also modify the disease process, demonstrating the role for
"moderator genes."
PMID- 9654608
TI - The neutrophil and preeclampsia.
AB - Endothelial injury is common to all pathological features of preeclampsia.
Neutrophil activation has been implicated in the pathophysiology of preeclampsia
and requires binding and transmigration of neutrophils through the endothelium.
This occurs via an interaction of endothelial adhesion molecules and surface
receptors on neutrophils. Upon activation, neutrophil granules are released, the
contents of which are capable of mediating vascular damage. In addition,
leukotrienes are synthesized, and superoxide is generated in a respiratory burst.
These products also provoke vascular damage. Neutrophil recruitment to the
endothelium involves express of P-selectin and released of platelet activating
factor from the endothelium. In preeclampsia there is evidence of an increase in
neutrophil activation with up-regulation of neutrophil integrin expression and
increased regulation of the protease elastase. Furthermore, these markers of
neutrophil activation correlate with established markers of disease severity. The
primary mechanism of neutrophil activation is unknown, but neutrophils in
preeclampsia appear to have normal motor activity. Several potential mechanisms
of neutrophil activation have been identified. They include up-regulation of
cellular adhesion molecules on the endothelial surface, increased generation of
tumor necrosis factor-alpha, and endothelial activation from hyperlipidemia. In
additional to activation of neutrophils in preeclampsia, there may be involvement
of the interleukin-6 and endothelin-1 in "priming" neutrophils for subsequent
superoxide production. Activated neutrophils are likely to play a large part in
the arteriopathy and endothelial damage associated with preeclampsia, but it is
unclear whether neutrophil activation is the cause or the consequence of
endothelial damage.
PMID- 9654609
TI - Oxidative stress and altered endothelial cell function in preeclampsia.
AB - Evidence continues to accumulate that oxidative stress is a mediator of
endothelial cell dysfunction and thus contributes to the cardiovascular
complications of preeclampsia. The mechanisms for the interaction of oxidative
stress and endothelial cell function have not been well defined. This review
explores potential vasoactive pathways that may be affected by oxidative stress
and have been reported to be altered in women with preeclampsia. In pathologic
conditions of oxidative stress, increased production of superoxide peroxide
anions and nitric oxide has been recognized to inactivate the nitric oxide as a
vasorelaxant as well as produce peroxynitrite, a potent oxidant. Increase
prostaglandin H (PGH) synthase activity resulting in vasoconstriction
predominates in models of oxidative stress. Peroxynitrite increases PGH synthase
activity in vitro, providing a potential, but as yet untested, link between
oxidative stress, nitric oxide, and PGH synthase pathway, leading to reduced
relaxation and increased constriction in the vasculature of women with
preeclampsia. Other vasoconstrictors (such as isoprostanes and endothelin) that
may be interrelated with oxidative stress and altered endothelial cell function
in preeclampsia are also discussed.
PMID- 9654610
TI - Dyslipidemia, iron, and oxidative stress in preeclampsia: assessment of maternal
and feto-placental interactions.
AB - The etiology and pathogenesis of the pregnancy syndrome preeclampsia remain
poorly understood. There is evidence that oxidative stress (am imbalance between
oxidant and antioxidant forces in favor of oxidants) occurs in preeclampsia, and
it has been hypothesized that reactive oxygen species or their metabolites
ultimately comprise the "defensive" vasodilatory, antiaggregatory, and barrier
functioning of the vascular endothelium. Oxidative stress may be point at which
feto-placental and maternal factors converge, resulting in the protean
manifestations of preeclampsia. This review highlights the evidence for maternal
dyslipidemia and altered iron kinetics in preeclampsia and gives a critical
assessment of their potential impact on disease progression. The theme is
developed that interaction of maternal components, particularly neutrophils and
oxidation-susceptible lipids, with placental cells and placental-derived factors
engenders feed-forward cycles of oxidative stress that ultimately cause
widespread endothelial cell dysfunction and its clinical manifestations.
PMID- 9654611
TI - Maternal-placental interactions of oxidative stress and antioxidants in
preeclampsia.
AB - This review addresses the general hypothesis that the pathogenesis of
preeclampsia is related to an imbalance of increased oxidative stress and lipid
peroxidation coupled to a deficiency of antioxidant protection. Evidence will be
presented that this imbalance is present in both the maternal compartment and the
placental compartment and that interactions between these two compartments result
in the clinical manifestations of this disorder. We suggest the following as a
scenario for the development of preeclampsia: Oxidative stress in the maternal
compartment affects the placenta in such a way as to bring about a decrease in
placental antioxidant enzyme protection. The oxidative stress in the maternal
compartment may be preexisting (e.g., obesity, diabetes, hyperlipidemia) or may
be caused by placental secretion of lipid peroxides. Decreased placental
antioxidant enzyme protection leads to a cascade of events in the placenta of
uncontrolled lipid peroxidation with increased thromboxane production and
increased tumor necrosis factor (TNF-alpha) production. Increased placental
secretion of lipid peroxides and/or TNF-alpha results in activation of leukocytes
as they circulate through the intervillous space. The activated leukocytes serve
as circulating mediators that link the increased oxidative stress of the placenta
with a widespread increase in oxidative stress and endothelial dysfunction in the
mother. In the third trimester, when the placenta is growing rapidly, the
mother's antioxidant capacity is no longer able to compensate, and the clinical
symptoms of preeclampsia appear.
PMID- 9654612
TI - Measuring HIV/AIDS case management.
AB - Studies of HIV/AIDS case management have been limited by their almost exclusive
focus on adults and by the limitations of available methodologies. This study
assesses the use of a time study methodology to measure the case management
activities of 20 case managers in two urban hospital pediatric and adult HIV/
AIDS clinics and in 3 community organizations. Case management activity was
sampled using a beeper case managers carried, which signaled randomly 8 times a
day over 5 consecutive days. When the signal "beeped", case managers checked on a
form the appropriate descriptor of their involvement in case management tasks and
with different clients. The results suggest that the Time Study methodology is a
useful and valid way of measuring case management.
PMID- 9654613
TI - Measuring case management for families with HIV.
AB - Case management has been recognized as a major way for coordinating the multiple
services needs for people with HIV/AIDS. Such coordination is required because of
the progressively debilitating nature of this chronic disease and the fragmented
health care and social services delivery system. One of the major problems with
the study of case management is the difficulty in actually measuring it. Another
major limitation has been the focus almost exclusively on adult models of
HIV/AIDS case management. This study was undertaken to assess the efficacy of a
time study methodology to measure differences in case management activities when
case managers work with families and when they work with individuals. Ten case
managers from two urban hospital pediatric and adult HIV/AIDS clinics and 10 case
managers from 3 community organizations participated. Case management activity
was sampled using a beeper carried by case managers which signaled randomly 8
times a day over 5 consecutive days. When the signal "beeped", case managers
checked off on a 1-page form the appropriate descriptor of their involvement
concerning task initiation, interaction, location, type, function as well as
information about client needs, HIV status, and family history. The results
suggest that the Time Study methodology is a useful and valid way of measuring
case management and of identifying differences in case mix, client need and
background, and case management techniques when case managers work with families
and with individuals.
PMID- 9654614
TI - An off-site orientation program for medical social workers.
AB - The health care system is a complex and demanding environment requiring an
acculturation process for all those who provide services under its aegis. Social
workers new to a medical setting, are faced with difficulties relating to all
aspects of their role: bureaucratic, professional and clinical. In an attempt to
ease their entry into the health care system, five social work administrators,
employed by the largest HMO in Israel, structured and facilitated an off-site
orientation program for new workers. A core group of 22 social workers
participated in the program, and in the final session, the participants evaluated
the course verbally and in an anonymous closed questionnaire. Feedback was mixed
and included the participants dissatisfaction with the reduction of the
experiential component of the sessions.
PMID- 9654615
TI - Family conferences as forums for decision making in hospital settings.
AB - Social workers in hospitals are often involved in family conferences where
patient, family members and hospital personnel meet together to exchange
information about the patient's condition and to plan for the future. In this
paper the complexities of these meetings as decision making arenas are discussed
and an outline of the three phases of family conferences--preparation, the
conference meeting and follow up--is presented. The final section reports on an
exploratory review of recent conferences as perceived by social workers from an
acute and rehabilitation teaching hospital. The social workers' comments indicate
that the conferences achieve the desired outcomes, especially for hospital staff.
In this hospital the conferences are more often used for providing family members
with information, and for collective decision making about the patient's future
care, than for providing information to the patients about their illness and
treatment.
PMID- 9654616
TI - Self-care and psychosocial adjustment of patients following cardiac surgery.
AB - This research examined the role of self-care behavior of 151 patients (aged 40 to
80) on general psychological distress at one year after coronary artery bypass
graft (CABG) surgery. A tested hypothesis was that self-care practices would be
associated with a lower level of distress one year after surgery. The results
supported the beneficial effect of self-care on psychological adjustment, after
controlling for the effects of the number of other chronic illnesses and post
CABG depression. The findings suggest that social work in health care and in-home
care may help promote the psychosocial recovery process following surgery.
PMID- 9654617
TI - Psycho-social aspects of serious renal disease and dialysis: a review of the
literature.
AB - The most severe form of kidney disease is renal failure, a life-threatening
condition known as end-stage renal disease (ESRD). Though social work
intervention is an integral part of the response to serious kidney disease, the
topic has been noticeably absent in the discipline's literature. This article
synthesizes the research on the psycho-social aspects of end-stage renal disease,
with a particular focus on dialysis patients at different stages of the life
cycle. Social work services are particularly important to dialysis patients
because (1) ESRD influences patients' psycho-social environments and (2) the
psycho-social environments in which ESRD sufferers live impact the course of the
disease and physical well-being. Intervention issues are discussed. The review
found that most research on this topic lacks adequate sampling to generalize to
the ESRD population. Future research needs to address this shortcoming and
increase sample sizes to allow for statistical controls.
PMID- 9654618
TI - Phospholipase A2 sensitivity of the dorsal root and dorsal root ganglion.
AB - STUDY DESIGN: This study was designed to characterize the effects of
phospholipase A2 on the neural response of dorsal root and dorsal root ganglion
in the anesthetized New Zealand White rabbit. OBJECTIVES: To examine the effects
of phospholipase A2 on the neural response of somatosensory neurons at the dorsal
root ganglion level. SUMMARY OF BACKGROUND DATA: Phospholipase A2 may be an
irritating component of disc tissue that is present in high concentration in
painful herniated discs, in synovial fluids, and in sera of rheumatoid arthritis
patients. Phospholipase A2 is inflammatory; however, its effects on dorsal roots
and dorsal root ganglion response have never been demonstrated. METHODS:
Surgically isolated dorsal roots and dorsal root ganglia from New Zealand White
rabbits were investigated by electrophysiologic techniques. Phospholipase A2
doses ranging from 100 to 400 U were applied on the mechanically sensitive
segments of the dorsal root ganglia, and responses to varying doses were
evaluated in relation to elapsed time. RESULTS: The application of phospholipase
A2 on the dorsal root ganglion resulted in possible neurotoxicity at doses more
than 375 U, with no significant effect at lower doses except for recruitment of
"silent units" at doses ranging from 200 to 340 U. CONCLUSIONS: Phospholipase A2
doses comparable to serum concentrations in human rheumatoid arthritis appeared
to be neurotoxic when applied to dorsal root ganglia. At lower doses, silent
units become activated that were not active before the phospholipase A2
application. These results suggest that dorsal roots and dorsal root ganglion may
be impaired by phospholipase A2, leading to sciatica and low back pain.
PMID- 9654619
TI - Biomechanical evaluation of translaminar facet joint fixation. A comparative
study of poly-L-lactide pins, screws, and pedicle fixation.
AB - STUDY DESIGN: Nine sheep cadaveric spines were used in this acute postoperative
model. OBJECTIVES: To compare the biomechanical performance of translaminar facet
joint fixation techique with that of cortical screws and bioabsorbable poly-L
lactide pins and with that of rigid pedicle screw fixation in the lumbar spine.
SUMMARY OF BACKGROUND DATA: Among numerous posterior spine fixation techniques,
pedicle screw fixation has been reported to be the most rigid construct and to
provide high fusion rate. Translaminar facet joint screw fixation is an
alternative to pedicle screw fixation and is the lowest profile construct that
achieves stabilization. The authors have developed a new concept involving
application of bioabsorbable poly-L-lactide pins to translaminar facet joint
fixation. Degradation in the stiffness of the implants with time may be
advantageous for fusion mass remodeling. METHODS: A total of nine sheep L2-L6
cadaveric spines were used. Each intact spine was nondestructively tested in
flexion-extension bending (+/- 5-Nm peak bending moment with 100-N axial
compression) on a modified testing machine. Loads were applied for 10-second
periods using sinusoid waveforms. After testing the intact spine, bilateral
fenestration was performed between L4 and L5 and the medial aspect of the facet
capsule was resected. The L4-L5 functional spinal unit was than stabilized by
five methods: translaminar facet joint fixation with smooth poly-L-lactide pins;
translaminar facet joint fixation with cortical screws; pedicle screw fixation
with the Texas Scottish Rite Hospital system; and without instrumentation, in
that order. Linear displacement of L4 inferior and L5 superior articular
processes in the sagittal plain (delta facet) and L4-L5 intervertebral rotation
in the sagittal plain (theta sagittal) were measured by the extensometers mounted
to the spine. Ranges of motion (delta facet and theta sagittal), neutral zones,
linear elastic zone stiffness, and the total energy absorption during the load
unload cycle (hysteresis) were calculated. RESULTS: By resecting the facet joint
capsules and ligamentum flavum, delta facet and theta sagittal were not increased
significantly, whereas the increase of neutral zones and hysteresis were
statistically significant. Compared with the intact spine, delta facet was
significantly reduced to 41% of normal with translaminar facet joint fixation
with poly-L-lactide pins, to 9% with translaminar facet joint fixation with
screws, and to 11% with the Texas Scottish Rite Hospital system. Neutral zones of
delta facet showed a similar pattern, and these differences were significant.
Regarding linear elastic zone stiffness, translaminar facet joint fixation with
screws provided a stiffer construct than did pedicle screw fixation in the
flexion loading mode, whereas pedicle screw fixation yielded higher values for
stiffness in extension loading. Translaminar facet joint fixation with poly-L
lactide pins increased linear elastic zone stiffness in extension loading, but
the increase was less than was achieved with the other constructs. CONCLUSIONS:
The facet joint is the only true articulation in the lumbosacral spine. It is
logical to fix this part directly to achieve spine fixation. Translaminar facet
joint fixation with screws show similar biomechanical performance to pedicle
screw fixation. Translaminar facet joint fixation with poly-L-lactide pins is
significantly less stiff than either type of screw fixation, but it also
restricts the facet joint and intervertebral motions significantly when compared
with the intact spine.
PMID- 9654620
TI - Morphometry of human neck muscles.
AB - STUDY DESIGN: Cadaveric dissections were used to study muscle morphometry.
OBJECTIVE: To describe systematically the musculotendinous lengths, fascicle
lengths, pennation angles, and physiologic cross-sectional areas of neck and
shoulder muscles implicated in head movement. SUMMARY OF BACKGROUND DATA: In
previous studies of neck-muscle anatomy, researchers described only a subset of
muscle features, often using crude or indirect methods. None used microdissected
muscles to correct measured parameters for the presence of multiple fiber
compartments, internal aponeuroses, or variations in fiber or sarcomere length
required for qualitative models of force-generating capabilities. METHODS: Muscle
mass, pennation angle, fascicle length, and sarcomere length were measured in 14
neck muscles from 10 human cadavers. Architecturally complex muscles with
multiple attachments were divided into subvolumes, and each subvolume was
examined from both the superficial and deep surfaces, Internal aponeuroses were
microdissected within muscles to characterize architectural specializations.
Physiologic cross-sectional areas were calculated from the morphometric data.
RESULTS: The neck musculature was architecturally complex. Many muscles crossed
two or more joints and had multiple attachments to different bones. In some, the
presence of tendons and aponeuroses was associated with specializations in
fascicle organization. Considerable interindividual variation was found in the
number and location of tendinous insertions of the scalenes and longissimus
capitis muscles. In addition, rhomboideus showed significant variations in its
size and shape. The cross-sectional areas of neck muscles from large and small
subjects did not scale proportionately with body height and weight, nor did
individual muscles with widely varying cross-sectional areas (0.3-15.3cm2) scale
from on subject to another. CONCLUSIONS: The accuracy of morphometry can be
improved by incorporating measurements made by microdissecting neck muscles. The
presence of aponeurotic attachments can greatly shorten fascicle length; failure
to identify such attachments can lead to underestimates of cross-sectional areas.
Accuracy of a generalized model of the neck is also improved by normalizing
sarcomere lengths in all muscles.
PMID- 9654621
TI - Shen instrumentation for the management of unstable thoracolumbar fractures.
AB - STUDY DESIGN: A retrospective study was carried out using Shen instrumentation,
which is a modified pedicle rod sleeve spinal system, to perform reduction and
fusion in patients with unstable thoracolumbar fracture. OBJECTIVES: To
demonstrate that the simple, locally made pedicle rod sleeve instrumentation is
as effective as conventional systems in the management of thoracolumbar
fractures. The current results are also compared with those reported in the
literature. SUMMARY OF THE BACKGROUND DATA: Many instrumentations, such as
Harrington, Luque, and Dick, have been used for the management of thoracolumbar
fracture in the past 2 decades. Every device has its advantages and disadvantages
based on clinical practice and the biomechanical mechanism of reduction. METHODS:
Between January 1991 and December 1995, 96 consecutive patients who had
experienced unstable thoracolumbar fractures were treated surgically with Shen
instrumentation, which consists of four components: superior pedicle screws,
distraction rods, sleeves, and inferior laminar hooks. Of these 96 patients, 76
were male and 20 were female (age range, 16-68 years; mean, 37 years). Thirty
patients had partial paraplegia and 38 patients had complete paraplegia,
according to the Frankel classification. Injury categories were as follows: 43
burst fractures, 26 flexion-compression fractures, 22 fracture-dislocation
injuries, and 5 flexion-distraction injuries. RESULTS: The average follow-up was
39 months (range, 24-60 months). Kyphotic deformity was corrected from 27.1
degrees before surgery to 4.2 degrees after surgery, translation was reduced from
30.7% to 0%, height of compressed vertebral bodies was restored from 52.3% to
96.5% of the normal height. Computed tomographic evaluation showed that the cross
canal area was restored from 48.1% before to 70.9% after surgery. Improvement of
neurologic function of more than one Frankel grade occurred in 90% of patients.
CONCLUSION: Based on the understanding of biomechanics and the present clinical
results, Shen instrumentation is as efficacious as conventional devices available
today and may serve as a cost-effective option for thoracolumbar injuries,
especially in a developing country.
PMID- 9654622
TI - Video-assisted thoracoscopic surgery versus open thoracotomy for anterior
thoracic spinal fusion. A comparative radiographic, biomechanical, and histologic
analysis in a sheep model.
AB - STUDY DESIGN: In this in vivo investigation, a sheep model was used to compare
the efficacy of a video-assisted thoracoscopic approach and a traditional
thoracotomy in promoting a successful interbody spinal arthrodesis. OBJECTIVES:
To compare the incidence of successful anterior spinal arthrodesis among three
stabilization techniques-iliac crest, Bagby and Kuslich device, and Z-plate-
performed using a video-assisted thoracoscopic approach and conventional open
thoracotomy approaches. SUMMARY OF BACKGROUND DATA: A clinical outcome study on
open versus endoscopic spinal fusion is not yet available. Moreover, no basic
scientific investigations have been conducted to determine whether the success of
an endoscopic arthrodesis is comparable to that of a conventional open procedure.
METHODS: Fourteen Western Crossbred sheep underwent three identical
destabilization procedures at T5-T6, T7-T8, and T9-T10, in which the anterior and
middle osteoligamentous columns of the spine were resected, followed by three
randomized reconstruction procedures using iliac autograft alone, and Z-plate
stabilization with iliac autograft. In seven sheep, the entire destabilization
reconstruction procedure was performed using a video-assisted thoracoscopic
surgical approach. In the remaining seven, the procedure was performed by
conventional open thoracotomy. RESULTS: Histomorphometric and biomechanical
evaluation demonstrated that the video-assisted thoracoscopic approach and open
thoracotomy arthrodesis had comparable bone formation and biomechanical
properties (P > 0.05). However, the Z-plate fusions, as a group, demonstrated
increased flexion-extension stiffness properties and trabecular bone formation
compared with the autograft and Bagby and Kuslich device fusions (P < 0.05).
CONCLUSIONS: Thoracic interbody spinal fusions performed by thoracoscopy have
demonstrated histologic, biomechanical, and radiographic equivalence to those
performed by a thoracotomy approach. However, in the endoscopy group,
intraoperative complications causing longer operative times, higher estimated
blood loss, and increased animal morbidity indicated a substantial learning curve
associated with the adoption of this surgical technique.
PMID- 9654623
TI - The lordotic effect of the OSI frame on operative adolescent idiopathic scoliosis
patients.
AB - STUDY DESIGN: A prospective evaluation of adolescent idiopathic scoliosis
patients undergoing operative treatment on the Orthopedic Systems Incorporated
(OSI; Jackson) frame. OBJECTIVES: To investigate prospectively thoracic,
thoracolumbar, and lumbar sagittal alignments in patients with adolescent
idiopathic scoliosis who undergo an instrumented posterior spinal fusion on the
OSI frame. SUMMARY OF BACKGROUND DATA: In several studies, it has been shown that
patient positioning on various operative frames is an important component of
ultimate lumbar sagittal alignment. However, these studies have all concentrated
on the lumbar spine, and no sagittal plane alignment data in adolescent
idiopathic scoliosis patients have been reported in the thoracic and
thoracolumbar junction as it relates to intraoperative positioning, correction
maneuvers and correlative postoperative results. METHODS: Thirty-nine patients
with operative adolescent idiopathic scoliosis treated with an instrumented
posterior spinal fusion on the OSI frame were prospectively evaluated. Standing
preoperative, intraoperative, and postoperative long-cassette lateral radiographs
were reviewed with regional and segmental Cobb measurements of the thoracic,
thoracolumbar junction, and lumbar spine obtained. RESULTS: Thoracic kyphosis (T1
T12) measured +34 degrees before surgery, +28 degrees during surgery, and +30
degrees after surgery, Thus, a statistically significant decrease was noted in
thoracic kyphosis secondary to prone positioning on the OSI frame ( P < 0.05).
Thoracolumbar spine measurements from T10 to L2 also showed a lordotic trend from
+2 degrees before surgery, to -4 degrees during surgery, to -8 degrees after
surgery, which was also statistically significant (P < 0.05). Total lumbar
lordosis from T12 to S1 remained relatively unchanged from -60 degrees before
surgery, to -59 degrees during surgery, to -60 degrees after surgery. However,
segmental lumbar lordosis measured from T12 to the lowest instrumented vertebra
showed a statistically significant increase in lordosis from -17 degrees before
surgery, to -19 degrees during surgery, to -23 degrees after surgery (P < 0.05).
Those patients in whom lumbar pedicle screws were used (vs. hooks alone) had the
greatest increase in lumbar instrumented lordosis. CONCLUSIONS: Performing
adolescent idiopathic scoliosis correction on the OSI frame tends to decrease
thoracic kyphosis, increase thoracolumbar lordosis, and increase segmental
instrumented lumbar lordosis, while it maintains total lumbar lordosis.
PMID- 9654624
TI - An unusual cause of low back pain? A case report.
AB - STUDY DESIGN: Case report. OBJECTIVE: To highlight the evaluation of a patient
with low back pain after an incidental radiographic finding clouded routine
management. SUMMARY OF BACKGROUND DATA: Greenfield filters have been used for 20
years with good results. Complications have been seen and documented, but the
natural history of filter placement in young patients is not fully appreciated. A
prong from a Greenfield filter embedded within a vertebral body has been reported
once as an incidental finding in a patient undergoing prophylactic monitoring for
recurrence of tumor. METHODS: A 31-year-old woman had a pulmonary embolus after
surgery for a benign adnexal mass. A bleeding complication occurred after
systemic anticoagulation, and a vena caval filter was placed to limit the
possibility of further emboli. The patient was referred to the orthopedic clinic
5 years later with low back pain and an unusual finding on computer tomographic
scan: One prong of the filter was embedded within a vertebral body. RESULTS: A
bone scan was obtained to evaluate the status of bone activity around the prong.
Bone reaction was not evident. Conservative management of her low back pain was
instituted, and after 2 years, the patient remains asymptomatic. CONCLUSION: The
overall use of vena caval filters has produced favorable results, although
numerous complications have been reported. All long-term sequelae have not been
completely identified.
PMID- 9654625
TI - Vertebral remodeling in eosinophilic granuloma of the spine. A long-term follow
up.
AB - STUDY DESIGN: In this study, 14 conservatively treated patients were reviewed who
had eosinophilic granuloma of the spine, which had been diagnosed on the basis of
histologic study of the vertebral lesion or of specimens from other sites in
patients with multiple involvement. The remodeling of the vertebral body was
studied in an average follow-up of 5.6 years. OBJECTIVES: To analyze the
remodeling process of the involved growing vertebral body in Langerhans Cell
Histiocytosis after conservative treatment and to assess the sagittal and frontal
profile of the spine at the end of growth. Fourteen patients, aged between 1.2
and 11.3 years, with spinal involvement of a Langerhans' cell histiocytosis were
treated in the department of orthopedics between 1980 and 1990. All patients had
immobilization of the affected region by a custom-made brace. Six patients with
symptomatic lesions had radiotherapy and four patients with disseminated disease
were treated with chemotherapy. Clinical and radiologic examinations were made at
regular intervals to evaluate the development of the vertebrae during the
remodeling process. SUMMARY OF BACKGROUND DATA: In the 14 patients, both sexes
were affected equally. The disease was located in the cervical spine in two
patients and in thoracic and lumbar vertebrae in seven patients each. Two
patients had two vertebral lesions. METHODS: The radiologic evolution of the 16
vertebral lesions was evaluated using follow-up standardized lateral radiographs.
The reconstitution of the vertebral height in the presence of vertebra plana was
calculated by measuring the ventral distance between the superior and inferior
margins of the vertebral body in relation to the adjacent uninvolved vertebra.
RESULTS: The measurements showed a growth rate of 1.5-6 (average, 3) in vertebrae
with vertebra plana and a growth rate of 1.1-2.7 (average, 1.4) in the unaffected
vertebra. The reconstitution of the vertebral height was between 18.2% and 63.8%
of the adjacent vertebrae before and between 72.2% and 97% after skeletal
maturity. CONCLUSIONS: The results demonstrate that conservative orthopedic
treatment with immobilization in a brace is sufficient to allow for optimal
vertebral remodeling. Partial to nearly complete reconstitution of vertebral
height was seen in all cases. Thus, operative treatment with curettage of the
lesion and bone grafting including multisegmental fusion with instrumentation is
not necessary. In instances with neurologic impairment, rarely seen in adults,
surgical decompression and short fusion of the spine is necessary. Nevertheless,
complete staging and biopsy are mandatory for an accurate diagnosis.
PMID- 9654626
TI - Spinal surgery before and after Paul Harrington.
PMID- 9654627
TI - Research: risks, benefits, and responsibilities. Presidential address.
PMID- 9654628
TI - SRS travelling fellowship.
AB - A 3-week tour of the Far East was coordinated by Dr. Ronald DeWald, senior
travelling fellow appointed by the Scoliosis Research Society. Three junior
fellows appointed by the Education Committee of the Scoliosis Research Society
accompanied him. The purpose of this fellowship was to develop a comaraderie and
exchange ideas, thoughts, and experiences in the field of spinal deformity.
PMID- 9654629
TI - Revision pedicle screws. Bigger, longer shims--what is best?
AB - STUDY DESIGN: To evaluate the effect of change in screw dimensions and hole
augmentation in pedicle screw revisions, the insertional torque was determined,
and results were compared with those in control specimens in an in vitro study
using cadaveric thoracolumbar spines. OBJECTIVES: To determine the best method of
salvage for failed pedicle screws, by evaluating the insertional torque after
placing a larger diameter or longer screw into a stripped hole. Use of a shim and
use of larger and longer screws were also investigated. Finally, the effect on
insertional torque of simply removing and replacing a pedicle screw in its
original hole was investigated. SUMMARY OF BACKGROUND DATA: The effects of using
bigger or longer screws and shims to salvage failed pedicles have been studied.
The interaction between how much larger, how much longer, and inserting with or
without shims, has not been well studied. Optimizing reinsertional torque through
the use of bigger screws risks exceeding the pedicle capacity. Using longer
screws risks violation of the anterior vertebral body, thereby placing the great
vessels and viscera at risk. By knowing the relative contribution of increase in
length and diameter, the surgeon can optimize the risk-benefit ratio. METHODS:
Eight cadaveric spines from T10 to S1 were harvested. The specimens underwent
radiographic screening and bone densitometry. A modified Latin square
randomization was designed to evaluate the screw diameters and lengths. Each
pedicle was its own control. A 35- x 6.5-mm screw was used as a control. Test
screws were placed after pedicle screw hole failure was achieved and documented
by stripping. For the test screws, the diameters were increased by 1 mm and 2 mm,
the lengths were increased by 5 mm and 10 mm. Shims were added randomly. The peak
insertional torque was measured for each control screw and test screw placement.
In addition, during each screw placement, the screw was removed and replaced to
determine the effect. RESULTS: Insertional torque, after the pedicle screw is
removed and replaced in the same hole, was decreased by 34% (P < 0.000005).
Increasing the diameter of the salvage screw by 2 mm caused the insertional
torque to be increased by 8.4% of the original. Increasing the length of the
screw did not improve the salvage screw insertional torque. There was an
interaction effect for the 1-mm increase in diameter and the increase in length.
At this diameter, increasing the length had a significant effect (P = 0.009) on
the salvage torque. Using a shim created no improvement in salvage insertional
torque (P = 0.77). There was a poor linear correlation between torque and bone
mineral density (r = 0.18) in these osteoporotic specimens. CONCLUSIONS: Removing
and replacing a pedicle screw in its original hole substantially decreases its
mechanical fixation. For pedicle salvage, increasing the diameter causes the
greatest restoration of strength. Shims had no effect in pedicle salvage in
osteoporotic specimens.
PMID- 9654630
TI - A logical coronal pattern classification of 2,000 consecutive idiopathic
scoliosis cases based on the scoliosis research society-defined apical vertebra.
AB - STUDY DESIGN: Two thousand consecutive idiopathic scoliosis records and
radiographs were reviewed for coronal pattern typing and categorization, based on
Scoliosis Research Society definitions of the apical vertebra. Apical frequency
was determined for each of the patterns identified, and represents a database
from a large series of cases for the already accepted Scoliosis Research Society
definitions. OBJECTIVES: To identify and numerically pattern-type a large series
of idiopathic coronal curves, for the basic purpose of written and oral
communication. Some pattern types were not described previously. SUMMARY OF
BACKGROUND DATA: Although spinal deformity must be considered three dimensional
for treatment in 1998, no comprehensive, databased, and user friendly coronal or
sagittal classification of idiopathic scoliosis has been reported. METHODS: Two
thousand idiopathic curve patterns from charts and radiographs were reviewed and
the coronal patterns categorized by the apical vertebra. The resulting
classification was tested for inter- and intraobserver reliability by 12 spine
surgeons and 6 orthopedic residents. Apical frequencies were determined for each
pattern type. RESULTS: Twenty-one pattern categories were identified, and all
were right or left mirror image patterns (except for a quadruple pattern) that
permitted separation into 11 types. Incorporating the widely recognized five
numbered King types mad pattern recognition simple. Interobserver reliability
testing was 98.2%. The left single thoracic curve pattern was included in this
classification because only 9 (20.4%) of 44 patients with left thoracic curves
had intraspinal pathology. CONCLUSION: Two thousand consecutive idiopathic
coronal curve patterns separated into eleven readily identifiable types, and
incorporating the widely referenced five King types, makes recognition simple for
purposes of identification and communication. Sagittal and 3D factors excluded
from this classification are equally important in the process of treatment
decisions. Apical frequency data determined in this study lends credence to
Scoliosis Research Society definitions for idiopathic curve patterns.
PMID- 9654631
TI - Somatosensory- and motor-evoked potential monitoring without a wake-up test
during idiopathic scoliosis surgery. An accepted standard of care.
AB - STUDY DESIGN: This was a retrospective study of 500 patients undergoing
corrective surgery between 1987 and 1997 for spinal deformity caused by
idiopathic scoliosis. OBJECTIVES: To report the sensitivity and specificity of
somatosensory-evoked and neurogenic motor-evoked potentials monitoring and the
requirements for an intraoperative wake-up test for all idiopathic scoliosis
surgeries at a single institution. SUMMARY OF BACKGROUND DATA: Intraoperative
monitoring is recommended for use during corrective spinal surgery. Accepted
monitoring standards and requirements for an intraoperative wake-up test are
still debated. METHODS: The study group consisted of 500 patients undergoing
corrective surgery for idiopathic scoliosis between 1987 and 1997. All patients
were monitored using somatosensory-evoked and neurogenic motor-evoked potential
techniques, using a standard protocol developed at this institution. RESULTS: The
false-positive rate (significant data change without postoperative neurologic
deficit) was 0.014% (n = 7). The true-positive rate (degradation of data that met
warning criteria, with a corresponding postoperative neurologic deficit) was
0.004% (n = 2). No false-negative results (normal data during with a
postoperative neurologic deficit) were seen. The sensitivity of combined
somatosensory-evoked and neurogenic motor-evoked potential data in predicting
neurologic status was 98.6%, and the specificity of normal data predicting normal
findings in a neurologic examination was 100%. CONCLUSION: Combined somatosensory
evoked and neurogenic motor-evoked potentials monitoring during idiopathic
scoliosis surgery represents a standard of care that obviates the need for an
intraoperative wake-up test when reliable data are obtained and maintained.
PMID- 9654632
TI - Nutritional depletion in staged spinal reconstructive surgery. The effect of
total parenteral nutrition.
AB - STUDY DESIGN: A prospective randomized study evaluating nutritional depletion in
spine surgery patients. OBJECTIVE: To determine whether use of total parenteral
nutrition (TPN) in patients undergoing staged spinal reconstructive procedures
could affect their nutritional parameters or decrease their complication rates.
SUMMARY OF BACKGROUND DATA: Several studies have shown that nutritional depletion
occurs after major spinal surgery and that patients undergoing staged spinal
surgery may be at particular risk of nutritional loss and its complications.
METHODS: Forty adult patients undergoing staged spinal reconstructive surgery
were randomized as to whether they received TPN postoperatively. Nutritional
parameters, including skin fold measurement and albumin, pre-albumin,
transferrin, and total lymphocyte counts, were obtained pre-operatively and at
regular intervals. RESULTS: Five patients did not complete the study, leaving 35
patients for analysis. There was a significant decrease in incidence of albumin
and pre-albumin depletion for the patients who did not receive TPN compared with
those who did receive TPN (P < 0.025, P < 0.006, respectively). Patients with
depleted albumin or pre-albumin counts were more likely to develop other
postoperative infectious complications such as pneumonia or urinary tract
infections (P < 0.035). There were no statistically significant differences in
wound complications in this small patient study. There were no complications
secondary to use of the TPN. CONCLUSIONS: For complex patients requiring staged
anterior/posterior surgery, TPN appears to significantly lessen the decrease in
nutritional parameters. Because depletion of nutritional parameters appears to
correlate with an increased likelihood of perioperative infectious complications,
use of TPN may result in a decrease of such complications in these patients.
PMID- 9654633
TI - Modified luque instrumentation after myelomeningocele kyphectomy.
AB - STUDY DESIGN: Treatment of congenital kyphosis in myelomeningocele is a difficult
problem. Current thinking supports kyphectomy and postoperative internal
fixation. OBJECTIVES: Since 1989, vertebral resection with modified Luque
fixation has been the procedure of choice for correction of myelomeningocele
kyphotic deformity at the author's institution. The study objective was to
evaluate long-term results with this technique. SUMMARY OF BACKGROUND DATA: Most
investigators agree that kyphotic deformity in myelomeningocele should be treated
with vertebral resection. There is less uniform consensus about postoperative
fixation. Reports in the literature support fixation with modified segmental
instrumentation. METHODS: Sixteen patients, observed for an average of 57.2
months (range, 36-94 months), underwent vertebral resection from the proximal
aspect of the apical vertebra cephalad into the compensatory lordotic curve.
Fixation was segmental instrumentation wired to the thoracic spine and anterior
to the sacrum. RESULTS: The average blood loss was 1121 mL (range, 450-2580 mL).
Kyphotic deformity averaged 111 degrees before surgery (range, 75-157 degrees),
15 degrees after surgery (range, -18-36 degrees) and 20 degrees at latest follow
up (range, -17-83 degrees). Loss of correction was 6 degrees (range, 0-27
degrees). Postoperative immobilization was with a thoracolumbosacral orthosis for
18 months. Complications occurring in 8 of the 16 patients were transient
headache, superficial wound breakdown, supracondylar femur fractures, and one
late infection secondary to skin breakdown that necessitated early rod removal,
resulting in some loss of correction. CONCLUSIONS: Kyphectomy is an excellent
method of correcting rigid kyphotic deformity in the patient with myelodysplasia.
Segmental spinal instrumentation provided three distinct advantages: rigidity of
the construct, greater correction of the deformity and low-profile
instrumentation.
PMID- 9654635
TI - Bracing of patients after fusion for degenerative problems of the lumbar spine-
yes or no?
AB - The majority of spine fusions currently performed are for degenerative
conditions. Controversy exists regarding whether to routinely brace patients
during the postoperative period. The benefits of a rigid orthosis have yet to be
documented in a scientific study, and the cost of a custom-molded orthosis can be
quite high. An extensive literature search reveals few articles dealing with the
subject, and none with an adequate study design to convincingly support or refute
the use of external braces. In addition to the questions of whether an external
brace is effective, the mechanism of action also remains unclear. It has been
difficult to document mechanical effectiveness, so perhaps the effect is
psychologic. In addition, it is possible that some, not all, fusion patients may
benefit from a brace--yet our ability to select such a patient is poor. As a
result, we have solicited the views of two experienced surgeons on the topic. Dr.
Connolly argues that an external orthosis is advisable in many cases; Dr. Grob
feels that the rigidity of internal fixation should be adequate to obviate the
need for external bracing.
PMID- 9654634
TI - Scoliosis in total-body-involvement cerebral palsy. Analysis of surgical
treatment and patient and caregiver satisfaction.
AB - STUDY DESIGN: A nonrandomized descriptive case series. OBJECTIVES: To analyze the
results of spinal fusion in patients with total-body-involvement cerebral palsy
to determine early and late outcomes, including caregiver satisfaction. METHODS:
Data from 79 to 100 patients with total-body-involvement spastic cerebral palsy
who underwent posterior Luque instrumentation, or anterior spinal fusion, or
both, were adequate to be included in the study. Functional status was evaluated
by physical examination, and a personal interview was conducted with the patient,
parents, and primary caregiver. RESULTS: Median follow-up was 4 years (range, 2
14 years). Late progression of scoliosis (> 10 degrees), pelvic obliquity (> 5
degrees), and decompensation (> 4cm ) were noted in more than 30% of the
patients. More than 75% of patients with late progression were skeletally
immature at the time of surgery and underwent a posterior procedure only. Twenty
one percent of the patients required a revision procedure because of disease
progression. Progression was not noted in any patient who underwent anterior
fusion (with or without anterior instrumentation) plus posterior instrumentation
from the upper thoracic spine to the pelvis. Eighty-five percent of parents or
caregivers were very satisfied with the results of surgery and noted a beneficial
impact of the patient's sitting ability, physical appearance, ease of care, and
comfort. CONCLUSIONS: To avoid late progression of trunk deformity in skeletally
immature patients, anterior spinal release and fusion combined with posterior
segmental spinal instrumentation and fusion from the upper thoracic spine to the
pelvis are recommended. Skeletally mature patients with good curve flexibility
can be treated with posterior instrumentation and fusion only. Skeletally mature
patients with large fixed curves benefit from an anterior-posterior procedure for
better correction of the scoliosis and pelvis obliquity. Despite the surgical
complexity and expected complications, the overall good surgical results and high
patient and caregiver satisfaction confirm that corrective spinal surgery is
indicated and is beneficial for most patients with total-body-involvement
cerebral palsy and scoliosis.
PMID- 9654636
TI - The statistics of smoking.
PMID- 9654637
TI - Uncovering the effects of smoking: historical perspective.
AB - Tobacco was introduced into Europe from America at the end of the fifteen
century. At first used primarily for medicinal purposes it came to be burnt in
pipes for pleasure on a large scale nearly 100 years later, at first in England
and subsequently in Europe and throughout the world. Pipe smoking gave way to the
use of tobacco as snuff and, in turn, to cigars and cigarettes at different times
in different countries until cigarette smoking became the dominant form in most
of the developed world between the two world wars. Societies were formed to
discourage smoking at the beginning of the century in several countries, but they
had little success except in Germany where they were officially supported by the
government after the Nazis seized power. In retrospect it can now be seen that
medical evidence of the harm done by smoking has been accumulating for 200 years,
at first in relation to cancers of the lip and mouth, and then in relation to
vascular disease and cancer of the lung. The evidence was generally ignored until
five case-control studies relating smoking to the development of lung cancer were
published in 1950. These stimulated much research, including the conduct of
cohort studies, which, by the late 1950s, were beginning to show that smoking was
associated with the development of many other diseases as well. The
interpretation that smoking caused these various diseases was vigorously debated
for some years but came to be generally accepted in respect of lung cancer by the
late 1950s and of many other diseases in the subsequent two decades. Cigarette
smoking has now been found to be positively associated with nearly 40 diseases or
causes of death and to be negatively associated with eight or nine more. In some
instances the positive associations are largely or wholly due to confounding, but
the great majority have been shown to be causal in character. The few diseases
negatively associated with smoking are for the most part rare or nonfatal and
their impact on disease incidence and mortality as a result of smoking is less
than 1% of the excess of other diseases that are caused by smoking. The most
recent observations show that continued cigarette smoking throughout adult life
doubles age-specific mortality rates, nearly trebling them in late middle age.
All the diseases related to smoking that cause large numbers of deaths should now
have been discovered, but further nonfatal diseases may remain to be revealed by
cohort studies that are able to link individuals' morbidity data with their
personal characteristics.
PMID- 9654638
TI - Lung cancer and passive smoking.
AB - The evidence from epidemiological studies, studies of biochemical markers of
exposure and toxicological studies, confirm that there is a causal association
between the risk of lung cancer and exposure to environmental tobacco smoke.
Nonsmokers can inhale and metabolize carcinogens in tobacco smoke and other
markers of environmental tobacco smoke inhalation (nicotine and cotinine) are
raised in nonsmokers exposed to environmental tobacco smoke. In epidemiological
studies of women who are lifelong nonsmokers, there is a statistically
significant excess risk of lung cancer (24%, 95% confidence interval 13-36%) from
exposure to environmental tobacco smoke from the spouse and this increases with
the number of cigarettes smoked and duration of the marriage. Misclassification
bias (women who smoke but claim to be lifelong nonsmokers) and dietary
confounding are unlikely to explain the association; after adjustment for both,
the risk of lung cancer from environmental tobacco smoke exposure was still
statistically significant. In any event, their effects on the risk of lung cancer
in the epidemiological studies are balanced out by allowing for background
exposure to environmental tobacco smoke (that is, other than from the spouse) in
the reference group; the excess risk after allowing for all three is an estimated
26% (95% confidence interval 7-47%), similar to the adjusted figure of 24%. In
Britain, about one in every six nonsmokers are exposed to tobacco smoke from
smokers in the home. Passive smoking is an avoidable cause of mortality and
morbidity. Prevention strategies to reduce the amount of cigarette smoking in
public places should be part of public health policy.
PMID- 9654639
TI - Difficulties in assessing the relationship between passive smoking and lung
cancer.
AB - Since 1981, numerous epidemiological studies have investigated the relationship
between passive smoking and lung cancer in nonsmokers. The overall evidence,
predominantly relating to women, indicates a weak association with the husband's
smoking and many reviewers have concluded that this demonstrates a causal effect
of exposure to environmental tobacco smoke (ETS). Interpreting weak associations
is notoriously difficult, however, and this paper reviews problems specific to
the ETS-lung cancer relationship. After describing how to select relevant studies
and appropriate data, the methods for combining evidence together ('meta
analysis') are discussed, and the need to investigate sources of heterogeneity is
emphasized. Separate consideration is given to various forms of bias that may
affect overall relative risk estimates, including misclassification of active
smoking status, confounding, systematic case-control differences, recall bias,
diagnostic bias and publication bias. Sections on dose-response, multiple ETS
exposure sources and other issues follow. The problems are illustrated from the
available literature. It is shown there is no significant association of lung
cancer with workplace, childhood or social ETS exposure or with smoking by the
wife. Though statistically significant, the association with husband's smoking is
weak and heterogeneous and varies widely according to various study
characteristics. The association is markedly weakened by the adjustment for
smoking misclassification bias and is likely to be affected by confounding and
other sources of bias. While the precise extent of all the biases remains
unclear, it seems impossible to conclude with any certainty that ETS causes lung
cancer.
PMID- 9654640
TI - Statistical methods in genetic research on smoking.
AB - A growing body of evidence suggests that genetic factors have an important
influence on the onset and course of smoking. Here we review some of the
statistical methods that have been used to test for genetic influences on smoking
behaviour, with a particular focus on studies of large national twin samples. We
show how many of the hypotheses that have been tested using a genetic model
fitting approach have also been reformulated using logistic regression models
that will be more familiar to epidemiologists. Such an approach is more easily
extended to allow for sociocultural, as well as genetic, influences on smoking
behaviour. Using either approach, data are consistent in indicating that
certainly in men, and possibly in women, genetic factors play an important role
in predicting which individuals who become cigarette smokers progress to being
long-term persistent smokers.
PMID- 9654641
TI - Cigarette smoking prevalence, cessation and relapse.
AB - This paper briefly reviews three aspects of cigarette smoking behaviour: recent
British trends in prevalence and cessation, tobacco dependence and the nicotine
withdrawal syndrome, and treatment for smokers using nicotine replacement
therapy. It concludes with a meta-analysis of the effect of relapse in nicotine
replacement trials. For many years, until 1994, smoking prevalence in the UK
declined at a steady rate but since the early 1980s uptake in the young has
remained high. This failure to curb recruitment in the young may be in part
responsible for the recent rise in all-age smoking prevalence. Cessation rates
are very low when compared with the proportion of smokers who wish to stop and
repeatedly try to do so. This disparity can be attributed to the addictiveness of
nicotine and the withdrawal symptoms which confront the would-be quitter. To
date, the most effective adjunctive aid for smokers trying to quit is nicotine
replacement therapy but even when abstinence for several months has been achieved
the risk of relapse remains high.
PMID- 9654642
TI - Steroids, gene expression, and apoptosis: recollections of contributions and
controversies.
PMID- 9654643
TI - Synthesis and stereochemistry of 8,13-diaza-2,3-dimethoxygona-1,3,5(10),9(11)
tetraen-12-one and D-homo derivatives.
AB - From the condensation reaction of O-methylbutyrolactim (2), O-methylvalerolactim
(3), O-methylcaprolactim (4) and O-methyl-4-t-butylcaprolactim (5) with ethyl 6,7
dimethoxy-alpha-[1-(1,2,3,4-tetrahydro-isoquinolyl)] acetate (1), 8,13-diaza-2,3
dimethoxygona-1,3,5(10),9(11)-tetraen-1 2-one (6) D-homo-derivatives (7-9), and
medium-sized ring cyclic diamides (10,11) were obtained. The stereoselective
reduction of compounds 6-9 by Adam's platinum catalyst afforded 8,13-diaza-2,3
dimethoxygona-1,3,5(10)-trien-12-one (12) and its D-homo derivatives (13-15). The
structures of the compounds obtained were established by NMR and X-ray
crystallographic analyses.
PMID- 9654644
TI - Hydroxylation of pregnenolone at the 7 alpha- and 7 beta- positions by mouse
liver microsomes. Effects of cytochrome p450 inhibitors and structure-specific
inhibition by steroid hormones.
AB - Hydroxylations of pregnenolone (PREG) at the 7 alpha-and 7 beta-positions have
been reported in numerous murine tissues and organs, including liver, and the
responsible cytochrome P450 (P450) species await identification. Using thin-layer
chromatography and gas chromatography-mass spectrometry and crystallization to
constant specific activity, we report identification of 7 alpha-hydroxy-PREG and
7 beta-hydroxy-PREG metabolites produced in mouse liver microsomes and kinetic
studies of their production with apparent KM values of 2.45 +/- 0.124 microM and
3.41 +/- 0.236 microM for 7 alpha- and 7 beta-hydroxylation, respectively.
Investigation of P450 inhibitors and of steroid hormone effects on both 7 alpha-
and 7 beta-hydroxylation of PREG showed that 1) different P450 were involved
because metyrapone and antipyrine inhibited solely 7 alpha-and 7 beta
hydroxylation, respectively; 2) P450 1A2, 2D6, 2B1, and 2B11 were not responsible
for 7 alpha and 7 beta-hydroxylation of PREG because respective specific
inhibitors furafylline, quinidine, and chloramphenicol triggered no inhibition;
3) P450 1A1 was responsible for only part of the 7 beta-hydroxylation of PREG
because alpha-naphthoflavone, which inhibits specifically P450 1A1, did not
suppress entirely 7 beta-hydroxylation while ketoconazole, antipyrine, and
metyrapone extensively decreased the 7 beta-hydroxylation; 4) comparison of these
findings with those obtained with brain microsomes suggests that tissue-specific
P450 species are responsible for the 7 alpha-and 7 beta-hydroxylation of PREG;
and 5) 7 alpha-hydroxylation of PREG may be shared with other 3 beta
hydroxysteroids such as isoandrosterone, 5-androstene-3 beta, 17 beta-diol, and
dehydroepiandrosterone, which acted in a competitive manner. Taken together,
these findings will be of use for identification of the P450 species responsible
for 7 alpha- and 7 beta-hydroxylation of PREG and for studies of their activities
in liver and other organs.
PMID- 9654645
TI - Studies on the hydrogenation of the progestagen dienogest in vivo and in vitro in
the female rabbit.
AB - The biotransformation of the progestagen dienogest (17 alpha-cyanomethyl-17 beta
hydroxy-4,9-estradien-3-one) was studied in vivo in female rabbits and in vitro
by liver homogenates from female rabbits and rats. In vivo, in the female rabbit,
3H-dienogest was the subject of an extensive biotransformation. A significant
difference between the composition of the urinary and biliary metabolite patterns
of dienogest was found. While in the urinary metabolite pattern more polar
metabolites dominated, in bile of animals with a bile fistula, a dienogest
metabolite of medium polarity was prevalent. This main metabolite of dienogest
was identified by MS, 1H- and 13C-NMR spectroscopy and CD measurement of an
enzymatic dehydrogenation product as the tetrahydro metabolite 17 alpha
cyanomethyl-5 alpha-estr-9-en-3 beta,17 beta-diol. Thus, in vivo, the 4,9-dien-3
oxo-19-norsteroid dienogest is hydrogenated to a 5 alpha H-9-en metabolite. In
vitro, however, 3H-dienogest was only poorly transformed by liver homogenates
from both species, whereas 3H-levonorgestrel and 3H-3-keto-desogestrel were
converted partially by liver homogenates from female rabbits and completely by
liver homogenates from female rats. The principal biotransformation reactions of
levonorgestrel and 3-ketodesogestrel were the reduction of the 3-oxo group to 3
OH and the 5 beta- and 5 alpha-hydrogenation of the 4-double bond by homogenates
of female rabbit liver and female rat liver, respectively. A dihydro metabolite
of dienogest, in which the 3-oxo group had been reduced to 3-OH, was isolated in
small amounts from the incubation with rabbit liver homogenate. The data indicate
that the enzymatic hydrogenation of the 4-double bond of the 4,9-dien-3-oxo
steroid dienogest is inhibited in vitro. The hindered hydrogenation reaction in
vitro has to be seen in association with the 9-double bond in the steroid
molecule.
PMID- 9654646
TI - Effect of sodium restriction on urinary excretion of cortisol and its metabolites
in humans.
AB - The adrenal gland is involved in the control of urinary sodium excretion mainly
via the secretion of the mineralocorticoid aldosterone. Although under certain
conditions glucocorticoid seem to be also involved in the regulation of sodium
homeostasis, there are contradictory reports on the relationship between cortisol
secretion and sodium intake. Given recent findings linking regulation of
physiological activity of steroids to the activity of specific enzymatic
pathways, we have examined changes in urinary excretion of cortisol and its
metabolites in eight healthy volunteers on a low sodium diet. Urinary steroids
were measured with specific radioimmunoassays after extraction and chromatography
(F and E) or after dilution (THF and THE). Excretion of cortisol (124 +/-41
nmol/day) was significantly lower on Day 2 (86 +/- 27 nmol/day, p < 0.01) and Day
7 (85 +/- 25 nmol/day, p < 0.01) of sodium restriction. On the same samples
calculated ratios of THF/F (55 +/- 15; 61 +/- 22; 68 +/- 21) and E/F (2.5 +/-
0.6; 2.8 +/- 1.4; 3.0 +/- 1.3) reflecting the activity of 5 beta-reductase and 11
beta-hydroxysteroid dehydrogenase, respectively, showed significant increases in
the former on both Days 2 and 7 and for the latter only on Day 7. This study
supports the notion that sodium restriction decreases urinary cortisol excretion
and provides evidence that increased activity of 5 beta-reductase and lowered
metabolism by 11 beta-HSD are presumably the mechanisms of this decrease.
PMID- 9654647
TI - Application of an improved ELISA assay to the analysis of urinary estrogen
metabolites.
AB - Work from Strang and other laboratories has established that the 2-/16 alpha
hydroxyestrone ratio is inversely correlated with the risk for breast and
cervical cancer. In order to measure these metabolites in urine samples, it is
essential to have an assay for these compounds that is both sensitive and
reproducible. The present paper describes such an ELISA assay, which overcomes
problems that existed in prior approaches to measuring these compounds. The new
ELISA procedure supplies greater sensitivity and reproducibility than earlier
assay procedures. The ELISA assay has also been found to correlate well with the
GC-MS procedure of Adlercreutz.
PMID- 9654648
TI - Effect of long-term treatment with aromatase inhibitor on testicular function of
adult male bonnet monkeys (M. radiata).
AB - The role/need for estrogen in regulating testicular function of adult male bonnet
monkeys (M. radiata) has been investigated by dosing orally a group of five
normal males 2.5 mgs of CGP 47645, a long-acting nonsteroidal aromatase inhibitor
(AI), once every 5 days for over 150 days. Such treatment resulted in a 10-fold
increment in nocturnal serum testosterone (T) levels, which were sustained for 85
days of treatment, and a twofold increment in basal serum T levels was present
throughout the 150 days of treatment. Analysis of ejaculated semen showed a
marked reduction (approximately 90%) in sperm counts in four out of five monkeys
between Days 55-85 of treatment. During this period, the motility score also was
markedly reduced from a normal score of 3-5 to 0-2. Flow cytometric analysis of
testicular germ cells obtained from biopsy tissue taken on Days 63 and 120
indicated a marked reduction only in elongating/elongated spermatid population
(compared to Day 0 values), suggesting inhibition in spermiogenic process.
Epididymal sperm maturation also seemed effected as sperm chromatin, on flow
cytometric analysis for decondensability following exposure to 5 mM
dithiotreitol, showed to be in a hypercondensed state. This study thus indicates
that estrogen has an important role in providing normal testicular and sperm
function in the primate.
PMID- 9654649
TI - Ginsenoside Rg1 down-regulates glucocorticoid receptor and displays synergistic
effects with cAMP.
AB - Ginsenoside-Rg1 (G-Rg1) from the roots of Panax ginseng C. A. Meyer has been
shown to bind to the glucocorticoid receptor (GR). To further explore the effect
of G-Rg1 binding to GR, a luciferase reporter gene containing two copies of a
glucocorticoid response element was constructed and transiently transfected into
FTO2B rat hepatoma cells. A dose-dependent induction of the reporter gene was
observed in response to G-Rg1, and the inductive effect was blocked by treatment
with the antiglucocorticoid RU486. In addition, both G-Rg1- and dexamethasone
(Dex)-induced transcription was synergistically enhanced by the treatment of
dibutyryl cAMP (Bt2-cAMP). G-Rg1 treatment also led to the down-regulation of
intracellular GR content, which was similar to the effect of Dex. By showing that
G-Rg1 down-regulates GR and induces GR-mediated transcription synergistically
with cAMP, we conclude that G-Rg1 is a functional GR ligand in FTO2B cells.
PMID- 9654650
TI - Development of potent non-estrogenic estrone sulfatase inhibitors.
AB - Estrogen levels in breast tumors of post-menopausal women are as much as 10 times
higher than estrogen levels in plasma, presumably due to in situ formation of
estrogen. The major source of estrogen in breast cancer cells may be conversion
of estrone sulfate to estrone by the enzyme estrone sulfatase. Thus, inhibitors
of estrone sulfatase have potential for the treatment of estrogen-dependent
breast cancers. Several steroidal agents have been developed that are potent
estrone sulfatase inhibitors, most notably estrone-3-O-sulfamate. These compounds
may have undesired actions, especially estrogenicity. Recently, non-steroidal
estrone sulfatase inhibitors have been designed that avoid the problems
associated with an active steroid nucleus; however, these have not achieved the
potency of estrone-3-O sulfamate. We have designed and synthesized a series of
compounds, 17 beta-(N-alkylcarbamoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (6a-d)
and 17 beta-(N-alkanoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (11a-d) that
combine the structural features of the steroidal estrone sulfatase inhibitors
with a membrane insertion region that should increase the affinity for the
sulfatase enzyme and decrease the estrogenicity of the steroid. We tested the
compounds for estrone sulfatase inhibition by measuring estrone sulfatase
activity in intact cultures of human breast cancer cells (MDA-MB-231). We tested
for estrogenicity by measuring growth of estrogen-dependent MCF-7 human breast
cancer cells. All of the test compounds (10 nM) substantially inhibited estrogen
sulfatase activity of intact MDA-MB-231 cells. Dose-response analysis indicated
an IC50 of approximately 0.5 nM for two of the compounds (6a and 11a). In the
test for estrogenicity, estrone and estrone-3-O-sulfamate significantly
stimulated MCF-7 cell growth. In contrast, neither the 17 beta-(N-alkylcarbamoyl)
estra-1,3,5,(10)-trien-3-O-sulfamates++ + nor the 17 beta-(N)-alkanoyl)-estra
1,3,5,(10)-trien-3-O-sulfamates stimulated growth of MCF-7 cells at a
concentration of 1 microM, indicating that they are not estrogenic at levels 2000
times greater than their IC50 for estrone sulfatase. Our data indicate the
utility of the new compounds for inhibition of breast cancer cell estrone
sulfatase activity. Further, our data support the concept that estrone sulfatase
inhibitors may be useful as therapeutic agents for estrogen-dependent breast
cancers.
PMID- 9654651
TI - Estrogenic effects of the synthetic aminoestrogen 17 beta-(5-hydroxy-1
pentylamino)-1,3,5(10)-estratrien-3-ol (pentolame).
AB - In this study, we investigated the effects of pentolame, a 17 beta-aminoestrogen
derivative, upon coagulation, serum LH, pituitary progestin receptors, uterine
weight, and endometrium morphological changes in the castrated female rat. Groups
of animals were subcutaneously (s.c.) injected with either estradiol (E2) (0.1 up
to 1000 micrograms/animal), pentolame (1 up to 1000 micrograms/animal), or the
vehicle alone daily for 5 consecutive days starting 2 weeks following
ovariectomy. Administration of pentolame (10 to 1000 micrograms/animal) increased
significantly (p < 0.05) the blood clotting time when compared with that obtained
in the group of control animals (EC50 582 micrograms). Pentolame (500 and 1000
micrograms/rat for 5 days) caused a significant inhibition (p < 0.01) of serum LH
levels (IC50 860 micrograms), which remained suppressed until Day 5 post last
injection. In addition, treatment with pentolame was able to restore in the
castrated female rat the presence of specific estrogen-dependent progestin
binding sites at the anterior pituitary level. The affinity constants and the
number of binding sites of pentolame-induced progestin receptors were similar to
those obtained with estradiol at equipotent doses (860 micrograms vs. 1
microgram/animal, respectively). Administration of the 17 beta-aminoestrogen
derivative resulted in a significant increase in uterine weight (EC50 420
micrograms) and endometrial characteristics were indistinguishable from those
observed in the group of rats treated with E2.
PMID- 9654652
TI - A little heart trouble. Mary Lasker and the founding of the National Heart
Institute.
PMID- 9654653
TI - Open hearts. The origins of direct-vision intracardiac surgery.
AB - Only 50 years ago, operating under direct vision within the walls of the living
human heart appeared to be a surgical problem with no great hope of solution.
However, technologic advances soon provided the necessary tools, and a safe,
reliable, and practical technique of performing surgery within the open heart
evolved in a series of stages. First, W.G. Bigelow espoused applied hypothermia
as a means of protecting the vital organs during direct cardiac repair--a
technique that F.J. Lewis then applied in correcting an atrial septal defect
under direct vision. This was followed by C.W. Lillehei's introduction and
application of controlled cross-circulation, which enabled the correction of more
complex cardiac lesions. Finally, the efforts of J.H. Gibbon and J.W. Kirklin led
to the creation of a reliable cardiopulmonary bypass apparatus, which enabled the
many subsequent achievements well recognized in the history of surgery.
PMID- 9654654
TI - New findings on the origin of the blood supply to the atrioventricular node.
Clinical and surgical significance.
AB - The anatomy of the heart's conduction system and of its blood supply have been
research topics for many years. However, several proposals have never been
demonstrated. In this paper, we describe 2 vascular conduits that have never
before been objectively shown to supply the conduction system. Twenty human
hearts from subjects aged between 15 and 65 years--with and without coronary
disease--were dissected after anterograde and retrograde injection with latex
butaclor E-650 by means of a technique developed by the authors. In 40% of these
hearts, Kugel's artery was found to supply the atrioventricular node. The right
descending superior artery supplied the atrioventricular node in 70% of the
hearts dissected. These findings may be of major significance both in clinical
cardiology and in cardiovascular surgery.
PMID- 9654655
TI - Repair of stenotic saphenous vein grafts in infrainguinal arterial
reconstructions.
AB - We describe a technique of repairing autologous vein grafts affected by segmental
stenosis. This technique can be of value both in reoperating on an old saphenous
vein graft implanted for infrainguinal limb revascularization and in harvesting
fresh saphenous vein in which an unexpected short-segment stenosis has been
encountered.
PMID- 9654656
TI - A no-touch technique for calcified ascending aorta during coronary artery
surgery.
AB - Despite improvements in cardiovascular surgery techniques over the years, the
incidence of neurologic complications has not declined, and stroke remains a
possible (and devastating) sequela to coronary artery surgery. In this report, we
describe a moderate hypothermic fibrillatory arrest technique that avoids cross
clamping or otherwise touching the aorta; use of the internal thoracic arteries
and the right gastroepiploic artery provides optimum revascularization and
minimizes the risk of cerebrovascular accident. Over a 1-year period, we used the
technique in 21 patients who had heavy calcifications of the ascending aorta. No
hemodynamic problems, lower-limb ischemia, or neurologic complications were seen.
Only 1 patient underwent reoperation (for bleeding), and another--whose
revascularization was incomplete--had a high postoperative level of myocardial
creatine kinase MB isoenzyme and a new Q wave, but no hemodynamic deterioration.
This technique seems reasonable, because it appears to provide good myocardial
protection and to reduce neurologic complications, without comprising myocardial
revascularization.
PMID- 9654657
TI - Coronary artery bypass grafting in patients with profound ventricular
dysfunction.
AB - Patients with severe ventricular dysfunction make up a special subset of patients
who undergo coronary artery bypass procedures. For these patients, the risk
associated with the bypass procedure is relatively high, but the opportunity-for
survival benefit is also greater. We studied 61 consecutive coronary artery
bypass patients with preoperative ejection fractions < or = 25%, and further
compared several subgroups: Group I (n = 30) ejection fractions ranged from 21%
to 25%; Group II (n = 23) ejection fractions ranged from 16% to 20.9%; and Group
III (n = 8) ejection fractions ranged from 10% to 15.9%. The overall mortality
rate was 8% (5/61), with no deaths in Group III. The 41% (25/61) of patients who
received left internal mammary artery conduits experienced a higher mortality
rate, yet it did not differ significantly from that of patients who received only
saphenous vein conduits. Intraaortic balloon pumps were placed in 48% (29/61) of
the patients, with a progressively higher incidence in patients with poorer
ventricular function (P < 0.05). Most intraaortic balloon pumps (59%) were placed
intraoperatively. Two patients underwent placement of left ventricular assist
devices, and 1 of these survived. Coronary artery bypass grafting in patients
with poor ventricular function carries a substantial, but acceptable, mortality
risk. Use of the left internal mammary artery did not improve perioperative
mortality, and may have a negative impact in the early postoperative period.
Intraaortic balloon pump use was most common in those patients with the worst
ventricular function. Prophylactic intraaortic balloon pump use may be justified
in candidates with ejection fractions < 20%.
PMID- 9654658
TI - Thrombolytics and left-sided prosthetic valve thrombosis. A case report.
AB - Prosthetic valve thrombosis is a well-known condition. Because surgical treatment
of prosthetic valve thrombosis is associated with a high mortality rate, the use
of thrombolysis as therapy for this condition has gained popularity in recent
years. In this article, we discuss the cases of 3 patients who presented to our
institution with left-sided prosthetic valve thrombosis between 1994 and 1997.
All 3 patients presented with New York Heart Association functional class III or
IV symptoms, and all were successfully treated with urokinase. The use of
thrombolytic therapy for left-sided prosthetic valve thrombosis is associated
with low mortality rates, and therefore is an attractive alternative to valve
replacement or thrombectomy. However, the risk of embolic and hemorrhagic
complications precludes the use of thrombolysis in patients with large thrombi
and in those with New York Heart Association functional class I and II symptoms;
for these patients, the risk associated with thrombolysis exceeds surgical
mortality rates.
PMID- 9654659
TI - Mycotic aneurysm of the popliteal artery secondary to tuberculosis. A case report
and review of the literature.
AB - Mycotic aneurysms of the popliteal artery are rare; 33 cases have been reported
in the literature. The treatment of choice is a large excision with extra
anatomic revascularization. In situ revascularization is sometimes possible. To
the best of our knowledge, tuberculosis has never been reported as a causal
factor of mycotic aneurysms of the popliteal artery. We report a case of a
recurrent tuberculous false aneurysm of the popliteal artery. After 2 attempts at
in situ revascularization, the femoral artery was ligated with no distal
ischemia.
PMID- 9654660
TI - Is nitroglycerin detrimental in patients with coronary artery ectasia? A case
report.
AB - During the management of acute myocardial infarction, we observed that clinical
and electrocardiographic indications of myocardial ischemia worsened upon
nitroglycerin infusion and were promptly relieved upon streptokinase infusion.
Subsequent coronary angiography revealed diffuse ectasia with no significant
stenosis. We discuss the possible pathophysiologic mechanisms by which
nitroglycerin might exacerbate ischemia in patients with non-stenotic ectasia,
and we present supporting data from other sources. We also attempt to identify
the characteristics of patients whose acute myocardial ischemia might be worsened
by the administration of nitroglycerin.
PMID- 9654661
TI - Improvement of reversible ischemia in severe post-transplantation coronary artery
disease.
AB - Coronary artery disease is a major cause of morbidity and mortality in patients
who have undergone heart transplantation. Patients are often asymptomatic during
the onset of the disease, and managing the disease is difficult. This report
describes the case of a patient with post-transplantation coronary artery disease
who, despite the severe, progressive appearance of the disease on angiographic
examination, showed evidence of autorevascularization and collateralization.
PMID- 9654662
TI - Spongy left ventricular myocardium in an adult.
AB - "Spongy left ventricular myocardium," or noncompaction of left ventricular
myocardium, is a rare disorder of endomyocardial morphogenesis. It is usually
seen in the pediatric population and is often associated with other congenital
cardiac malformations. We describe an adult with noncompaction of left
ventricular myocardium without associated congenital cardiac anomalies.
PMID- 9654663
TI - Symptomatic lipoma in the right atrial free wall. A case report.
AB - Benign non-myxomatous neoplasms of the heart are rare, and lipomas are among
those least often encountered. We report the case of a 38-year-old man who
presented with palpitations of recent onset, and was found to have a lipoma
attached to the free wall of the right atrium. The successful surgical excision
of the lipoma is described.
PMID- 9654664
TI - Polymorphic regurgitation jets in a flail mitral valve.
PMID- 9654665
TI - Transcatheter alcohol ablation of the septum in hypertrophic cardiomyopathy.
PMID- 9654666
TI - Persistent left superior vena cava.
PMID- 9654667
TI - [Early days and path of thoracic ultrasound].
PMID- 9654669
TI - [Effects of extracorporeal ultrasound shockwaves on the relatively mature embryos
of the teleost Oryzias latipes].
AB - Exposure to low-energy ultrasound shock waves (1000 impulses at a frequency of
2/sec and an energy density of 0.08 mj/mm2; peak positive/negative pressure 16/-7
MPa; pulse duration about 10 musec) led to the following alterations in the cells
and tissues of stage 35 embryos of Oryzias latipes ranked according to their
extent: (1) In various tissues, especially in the trunk musculature, orthodox
mitochondria were transformed into condensed (= low energy) mitochondria. (2)
Nuclear envelopes and sarcoplasmatic reticulum of muscle fibres as well as
endoplasmatic reticulum of epidermal ionocytes were often vesicularly dilated.
(3) Muscle fibres in the trunk musculature began to separate from each other.
Epidermal intercellular spaces were enlarged and increased in number. (4)
Destruction of vessels and haematomas were observed in the circulatory system of
the yolk sac. (5) Necroses up to total disintegration were found in various
organs of the body cavity (intestine, liver, spleen). The less serious
alterations (1 and 2) occurred in organs completely surrounded by other tissues.
Major damages (4 and 5), however, affected only organs with free outer and inner
surfaces, probably explained by cavitation and jet stream phenomena within the
adjacent fluids.
PMID- 9654670
TI - [Ultrasound-controlled interstitial high frequency thermotherapy (HFTT)--in vitro
studies of the bovine liver].
AB - PURPOSE: Sonographically-guided Radio-Frequency Tissue Ablation-applied with a
percutaneously placed needle can be used for the palliative treatment of primary
or secondary liver tumours. In vitro experiments were carried out to establish
the relations of the coagulation zone to histologic findings and sonographic
appearance. METHOD: Fresh bovine livers were obtained and radio-frequency was
applied under ultrasound guidance. The coagulation zone was dissected and
examined by determining its three-dimensional diameters (macroscopically) and the
histologic appearance of the coagulation margin to the surrounding tissue. In our
series of 50 experiments the application time ranged from 30 seconds to 10
minutes. RESULTS: The coagulation zone increased with increasing application time
in a way that can be described as a negative logarithmic function. The largest
volume was 4 x 5 x 5 cm (length, width, depth) approximating 50 ml. It was no
problem to judge the coagulation zone sonographically. The macroscopically and
sonographically determined width and length correlated with coefficients of 0.90
and 0.96. Microscopically the coagulation necrosis showed sharply outlined
margins without any vital cells. CONCLUSION: Radio-Frequency Tissue Ablation
applied under sonographic guidance has certain features which seem to make it a
promising method for the palliative treatment of primary and secondary tumours of
the liver.
PMID- 9654671
TI - [Ultrasound hip joint screening in newborn infants. Is twin pregnancy a risk
factor for dysplasia?].
AB - PURPOSE: This study aimed at investigating whether twin pregnancy is a risk
factor for congenital dysplasia of the hip. METHOD: From 1987 until 1994 the hips
of 3739 (1902 male, 1837 female) newborn were examined by ultrasound (screening)
according to Graf's technique. We compared the results of twins and the other
newborn (non-twins). The examinations were performed by 19 physicians. 73 (2%) of
the newborn were twins (29 male, 44 female). RESULTS: In the group of 3666 non
twins we found the types of hip IIa (alpha < 55 degrees) to IV (Graf's
classification) in 237 (6.5%) newborn: 136 (3.7%) right side/183 (5.0%) left
side. Only 2 (2.7%) of the 73 twins showed these types of hip. We found 4%
(149/3739) breech presentations at birth in the entire group. 3.9% (141/3666) in
the group of non-twins and 11% (8/73) cases in the twin group. 5.2% (190/3666) of
the non-twins and 2.7% (2/73) of the twins required a treatment with abduction
orthosis or Pavlik harness. CONCLUSION: This report shows that the types of hip
IIa (alpha < 55 degrees); IIc; D; IIa, IIb and IV according to Graf and a
required treatment in twins was significantly not more frequent than in the other
newborn (non-twins), although twins showed more often a breech presentation at
birth. The different kind of breech position in twins (hips and knees in flexion,
legs and feet parallel) and non-twins (hips in flexion, knees in extension) could
be one reason for these results. Besides, non-twins assume their breech position
earlier than twins with a consecutively longer period of time of mechanical
stress on the hips.
PMID- 9654672
TI - [Preoperative axilla sonography in breast tumor suspected of malignancy--a
diagnostic advantage?].
AB - PURPOSE: To assess the value of preoperative axillary sonography possibly
malignant for breast tumours. METHOD: We performed preoperative axillary
sonography on 89 patients with suspicious breast tumours. In 78 cases, among
which there were 74 invasive carcinomas, the surgery that followed included an
axillary lymph node dissection and a comparison with the histology was possible.
RESULTS: The sonographic detection of axillary lymph node metastases has a
sensitivity of 90% and a specificity of 91.7% in relation to all tumour stages
and a sensitivity of 100% and specificity of 89.6% in relation to T1 tumours. In
our analysis, therefore, it is vastly superior to a clinical examination of the
axilla. CONCLUSION: Ultrasonography is an accurate imaging method for the
diagnosis of axillary lymph node metastases. Broadening this analysis to include
more patients will validate this conclusion. The results of our preliminary study
suggest that this diagnostic method could help reduce unnecessary radical surgery
in the treatment of breast cancer.
PMID- 9654673
TI - Lung sonographic findings in patients with suspected pulmonary embolism.
AB - PURPOSE: To assess the feasibility and diagnostic performance of lung
transthoracic sonography in patients with suspected pulmonary embolism. METHOD:
In a prospective clinical study we compared sonographic findings of the
peripheral lung with various scintigraphic gradings and D-dimer plasma
concentrations. One hundred and nineteen consecutive patients with clinical signs
of pulmonary embolism were investigated within 24 hours of the onset of symptoms.
RESULTS: Seventy patients with suspected pulmonary embolism (59%) had sonographic
lesions, which were echo poor, homogeneous and rounded or wedge-shaped with a
hyperechoic reflexion in the centre. Of the patients with high-probability
scintigraphic scans 86% had such sonographic lesions as had 79% with
intermediate, 64% with low-probability and 33% with normal scintigraphic scans.
Of the patients with positive sonographic findings and normal or low-probability
scans only a minority (14%) had negative D-dimer tests. CONCLUSION: We found a
high rate of specific sonographic lesions in patients with suspected pulmonary
embolism when investigating the peripheral lung with ultrasound.
PMID- 9654674
TI - [Optimizing antrum planimetry for ultrasound determination of gastric emptying
using emptying function reference lines].
AB - Previous studies have shown high inter- and intraindividual variation
coefficients (Vkinter; Vkintra) of the gastric emptying time t(end) determined by
sonographical antrum planimetry. PURPOSE: Are there new parameters reflecting the
functional process of gastric emptying? METHOD: Gastric emptying of 300 ml water
was studied in 20 healthy volunteers by sonographical antrum planimetry. 10
volunteers were examined a second time on another day. RESULTS: High variation
coefficients Vkinter (42%) and Vkintra (31%) could be demonstrated. Moreover, a
correlation of r = +0.922 between tend and the maximal percentual increase of the
antral area was evident. This relation is introduced as the functional-emptying
line (FEL). CONCLUSION: Using the functional aspects of FEL, gastric emptying can
be studied sonographically under functional aspects.
PMID- 9654675
TI - [Mucinous cystadenoma of the appendix].
AB - A 63-year old female patient was admitted with a unclear abdominal ultrasound
scan. Despite all our diagnostic examinations, the diagnosis--mucinous
cystadenoma--was first established during surgery by intraoperative histological
evaluation. We discuss the diagnostic possibilities and therapeutic approach.
PMID- 9654676
TI - Sonographic appearance of an appendix carcinoma.
AB - Malignant appendix tumours are rare entities. Especially adenocarcinomas, which
only appear in about 10% of appendix tumours, are very seldom. Preoperative
diagnosis is very difficult due to a lack of typical clinical signs and a
clinical appearance mimicking perforated appendicitis. Nevertheless, sonography
is able to show indirect signs and therefore it can provide the surgeon with more
information for a better operative treatment.
PMID- 9654677
TI - [EFSUMB tutorial: thermal and mechanical indices].
PMID- 9654678
TI - HSV molecular biology: general aspects of herpes simplex virus molecular biology.
AB - Comparison of the herpes simplex virus type 1 (HSV-1) DNA sequence with that of
other alpha, beta and gamma-herpesviruses, allied with molecular genetic studies
have greatly increased understanding of the HSV genome and the functions encoded
by individual virus genes and has facilitated the development of rational
antiviral strategies. Here we review the coding content of the HSV-1 genome and
identify: genes encoding structural components of the capsid, tegument or
envelope; genes whose products are essential for growth in tissue culture; and
genes that are conserved between members of the alpha, beta and gamma
herpesvirinae. The HSV lifecycle and the main regulation cascade is discussed and
genes that present targets for antiviral intervention identified. The protein
content of the infectious virion particle is reviewed and compared with that of
two additional non-infectious HSV-related particles species (L-particles and pre
DNA replication particles (PREPs)). The potential of HSV-1 L particles and PREP
particles as DNA-free HSV-1 vaccine candidates and the desirability of deleting
specific gene products from live HSV vaccines is discussed.
PMID- 9654679
TI - Methods for the detection of non-random base substitution in virus genes: models
of synonymous nucleotide substitution in picornavirus genes.
AB - A substantial fraction of phylogenetic divergence between closely related RNA
virus genes is generally accounted for by synonymous (non-amino acid changing)
point mutation. Viral evolution may be a complicated phenomena, governed by many
different processes. However in this study we ask whether there are any
properties in the patterns of synonymous nucleotide substitutions in three
different Picornavirus genes that permit the process of accumulation of
synonymous point mutation in these genes to be distinguished from some of the
simplest most basic evolutionary models. We conclude that while the observed
patterns in the occurrence of synonymous point substitution are consistent with
those predicted by a model in which base mutation is equi-probable along a gene,
and the probability of synonymous substitution determined only by local codon
usage, some patterns in the actual nucleotides exchanged remain to be explained.
PMID- 9654680
TI - Transcription analysis of porcine circovirus (PCV).
AB - This study focuses on gene expression of porcine circovirus (PCV) in order to
identify viral genes and their corresponding mRNA transcripts. By northern blot
analysis, the existence of three mRNAs could be demonstrated. Two mRNAs are
encoded by the viral (-)-strand and one is encoded by the viral (+)-strand. The
(+)-strand encoded mRNA transcript is 990 nucleotides (nt) long and corresponds
to the open reading frame (ORF) 1, as shown by S1 mapping. The start point of
this transcript is located at pos. 1238, as determined by primer extension
analysis and rapid amplification of cDNA ends (RACE). The transcript is spliced
as shown by direct reverse sequencing and RACE. It contains an untranslated
"leader"-sequence 119 nt in size (pos. 1238 to 1120) which is joined to exon 2 of
the ORF 1 transcript at pos. 737. The transcriptional regulatory elements have
been identified functionally by CAT assays. They are located within a 258 base
points (bp) fragment (pos. 1168 to 1425).
PMID- 9654681
TI - The gene 4 of rice yellow stunt rhabdovirus encodes the matrix protein.
AB - The complete nucleotide sequence of the gene 4 of rice yellow stunt rhabdovirus
(RYSV) was determined from cDNAs corresponding to the viral genomic RNA. Gene 4
is 913 nucleotides (nt) long, comprising a 17-nt untranslated 5' region, a 786-nt
open reading frame encoding a polypeptide with a molecular mass of 29,125 Da, and
a 110-nt untranslated 3' region. Western blot analysis of the RYSV proteins using
the antiserum raised against the protein expressed from the cloned gene in
Escherichia coli indicates that gene 4 encodes the M protein of RYSV. Comparisons
of the deduced amino acid sequence of the M protein of RYSV with those of other
rhabdoviruses revealed no significant homologies. However, it shared a similar
basic property and a similar distribution of charges with the other rhabdovirus
matrix proteins and showed a relatively closer relationship to the sonchus yellow
net virus (SYNV) M1 protein.
PMID- 9654682
TI - Biological and genetic differences between lung- and brain-derived isolates of
maedi-visna virus.
AB - During the epidemic caused by maedi-visna virus (MVV) of sheep in Iceland, the
pulmonary affection, maedi, was the predominant clinical manifestation. In some
flocks, however, a central nervous system (CNS) affection, visna, was the main
cause of morbidity and mortality. As there is only one breed of sheep in the
country, host factors did apparently not play an important role in the different
clinical manifestations. To obtain some information on possible viral genetic
determinants of neurotropism and neurovirulence we studied both phenotypic and
genotypic properties of two maedi-visna virus strains; a strain that was
originally isolated from the brain of sheep with encephalitis (visna), and
another strain isolated from the lungs of a sheep suffering from pneumonia
(maedi). The brain isolate was found to grow faster in sheep choroid plexus cells
than the lung isolate, whereas the growth rate in macrophages was similar for the
maedi and visna virus strains. Intracerebral inoculation indicated that the visna
virus isolate induced more severe brain lesions than the maedi isolate. In
addition, a pathogenic molecular clone derived from a visna strain
(KV1772kv72/67) was tested for growth in sheep choroid plexus cells and
macrophages. The molecularly cloned virus retained the fast growth rate in
choroid plexus cells. The nucleotide sequence of the env gene and the U3 of the
LTR was determined for the maedi strain and compared to that of the visna
strains. There was an 11.7% difference in deduced amino acid sequence in the Env
protein and a 6% difference in the LTR. The molecular clone KV1772kv72/67 will be
a useful reagent for characterization of viral determinants of cell tropism in
vitro and possibly neurovirulence in vivo.
PMID- 9654683
TI - Phylogenetic analysis of triple gene block viruses based on the TGB 1 homolog
gene indicates a convergent evolution.
AB - The complete nucleotide sequence of the triple gene block one (TGB 1) of
cymbidium mosaic potexvirus (CymMV) was compared to those from other potex-,
carla-, furo- and hordeiviruses. Seven conserved motifs in the TGB 1, including
the ATP-GTP binding domain (P-Loop) consensus GXXGKTSTS, were found in all four
virus genera. We propose that all TGBV can be classified into phylogenetic
clusters based on their TGB 1 homolog genes. These clusters can be further
delineated to form subgroups. The first cluster comprises the potexviruses which
are further subdivided into three subgroups; BaMV, FMV, PlaMV and PapMV (subgroup
Ia); CymMV, PAMV, NMV, SMYEaV and WC1MV (subgroup Ib) and PVX (subgroup Ic). The
second cluster comprises carlaviruses with a dual subgrouping; CVB, LSV, PVM, PMV
and ASPV (subgroup IIa) and LVX (subgroup IIb). The third cluster carries the
most diverse of TGBV comprising furoviruses PCV, PMTV and BSBV (subgroup IIIa)
and hordeiviruses PSLV, BSMV and LRSV (subgroup IIIb). The phylogenetic
relationships of triple gene block viruses (TGBV) based on the TGB 1 homolog gene
indicates a convergent evolution.
PMID- 9654684
TI - Strawberry vein banding virus--definitive member of the genus Caulimovirus.
AB - The complete DNA sequence (7876 nucleotides) of strawberry vein banding virus
(SVBV) has been determined. Seven open reading frames are detected that
potentially code for proteins of calculated weight 37.8; 18.3; 16.6; 56.0; 81.1;
59.0 and 12.6 kDa, respectively. Their position on the viral genome is the same
as that of the corresponding proteins on the cauliflower mosaic virus (CaMV)
genome. Phylogenetic analysis based on the amino acid sequence of this protein
shows a closer relationship of SVBV with CaMV, figwort mosaic virus and carnation
etched ring virus than with other caulimoviruses.
PMID- 9654685
TI - Molecular characterization of the 3' noncoding region of classical swine fever
virus vaccine strains.
AB - The genomes of classical swine fever virus (CSFV) vaccine strains are poorly
characterized, and the mechanisms for their attenuation remain unknown. The aim
of the present study was to characterize the 3' noncoding region (3' NCR) of a
number of attenuated vaccine strains of CSFV in order to examine changes in the
viral genome after attenuation. The results showed that the 3' NCR:s of Porcivac,
Rovac, Russian LK and original Chinese vaccine strain contain insertions very
similar to that present in the published nucleotide sequence of the C-strain.
Phylogenetic analysis showed that the vaccine strains Porcivac, Rovac and Russian
LK vaccine were closely related to each other, but that these three strains
showed a distant relationship with two tested variants of the Chinese vaccine
strain (C-strain and original Chinese vaccine). The 3' NCR insertion is not
likely to be a marker for attenuation of the virus, since many CSFV vaccine
strains do not contain the insertion. The fact that the insertions occur in
lapinized vaccine strains suggests that these genetic segments were incorporated
during the adaptation of the virus to the rabbit host system.
PMID- 9654686
TI - Characterization of bovine adenovirus type 3 early region 2B.
AB - We have determined the nucleotide sequence of a 6999 base pair region of bovine
adenovirus-3 covering map units 9.0 to 29.17, which contained the adenovirus
homologs of IVa2 protein and the DNA replication proteins, precursor of terminal
protein and DNA polymerase proteins. Analysis of the sequence for cis-acting
elements suggests that transcripts of DNA polymerase and precursor of terminal
protein are 3' co-terminal. In addition, this region also contains major late
promoter sequence. The sequence to the left of IVa2 contains the ORF of pIX with
a potential TATA box immediately upstream and two polyadenylation consensus
signals immediately downstream of the ORF.
PMID- 9654687
TI - Nucleotide sequence of the inter-structural gene region of feline infectious
peritonitis virus.
AB - The sequence of the region located between the S and M glycoprotein genes of the
79-1146 strain of feline infectious peritonitis virus (FIPV) is presented. The
inter-structural gene region encodes 3 open reading frames (ORFs), termed ORFs
3a, 3b and 4, with nucleotide sequences conforming to the minimum conserved
transcription signal upstream of each. An additional ORF, 3x, partially overlaps
the 3' end of ORF 3a. The FIPV interstructural gene region is identical in length
when compared to the Insavc-1 strain of canine coronavirus (CCV) but differs from
various strains of transmissible gastroenteritis virus (TGEV) by the presence of
deletions and insertions. The sizes of ORF 3a and 4 are conserved in FIPV, TGEV
and CCV. However, as with CCV, the FIPV ORF 3b is truncated in comparison with
TGEV.
PMID- 9654688
TI - [Alcoholism--the accepted addiction].
PMID- 9654689
TI - The role of (auto-) immunity in atherogenesis.
AB - Recent data from different laboratories have provided evidence that the first
stages of atherosclerosis are inflammatory in nature. Research in the last
decades on this multifactorial disease has primarily focussed on the role of
lipids, with only a few anecdotal findings suggesting the involvement of the
immune system in atherogenesis. Within the group of antigens that may be
responsible for this immunoactivation during atherogenesis, heat shock protein
(hsp) 65/60 became a serious candidate based on the fact that immunization] of
normocholesterolemic rabbits with hsp65 leads to the development of
arteriosclerotic lesions in the aortic intima and these primary inflammatory
lesions are aggravated by a cholesterol-rich diet, thus completely resembling
human fatty streaks and atherosclerotic plaques. Furthermore, T cells in
atherosclerotic lesions of rabbits have been shown to react specially with
mycobacterial hsp65, suggesting that cell-mediated immune responses to hsp60 are
also involved in the pathogenesis of this disease In a large epidemiological
study we demonstrated that serum antibodies to mycobacterial hsp65 were
significantly increased in clinically healthy subjects with sonographically
demonstrable carotid atherosclerosis. These antibodies crossreact with human
hsp60. Thus further elucidation of the role of the role of the immune system in
atherogenesis could enhance our understanding of the mechanism of this vascular
disorder, and may lead to new therapeutic strategies for atherosclerosis.
PMID- 9654690
TI - [Incidence of alcoholism and problem drinking in Austria].
AB - The prevalence of problem-drinking and alcohol dependence in Austria was assessed
on the basis of two random samples of the general population drawn in 1995
(n=216) and in 1996 (n=531). Measurements were performed using the CAGE
questionnaire (Mayfield et al. 1974). Both cut-off points (> or = 1, > or = 2) of
the CAGE were used. Both samples showed a very similar prevalence of alcoholism.
2.2% (95% confidence interval 1.1-3.9%) of the Austrian adult population could be
regarded as alcohol dependent (four positive CAGE answers). Using a cut-off > or
= 2, 16-24% of the general population were rated as problem drinkers. The ratio
of male to female problem drinking was found to be 3:1; this ratio increased to
4:1 for alcohol dependence. Subjects aged 18 to 59 years were found to be at
greatest risk for problem drinking. Alcohol dependence showed an equal
distribution among all age groups with a peak prevalence of 3.7% among 45 to 59
year-olds. Significant differences in test scores were found for gender in both
samples, and for age in one sample; marital status had no impact on test scores.
The findings reported in this study partly confirm the results of Austrian
alcohol consumption surveys. Although our prevalence estimates rely on self
report and need to be validated by future epidemiological interview studies, the
results indicate that alcoholism and problem drinking pose a major public health
problem.
PMID- 9654691
TI - [Bone lengthening and soft tissue correction using the Ilizarov technique].
AB - From March 1989 to September 1995 at the Department of Orthopedic Surgery at the
Vienna General Hospital 31 limb-lengthenings or corrections of the soft-tissue
(contractions of joints, clubfeet) using the Ilizarov method were performed. 15
patients have already finished growth. All complications were analysed according
to Paley's classification. The tibia-group (n=13) reached an average lengthening
of 3.5 cm (2-5.7 cm) [16% (6-35%) of the initial length] with a healing index of
1.7 mo/cm and a complication rate of 42%. In the femur-group (n=8) a mean
lengthening of 5.4 cm (2.5-9.4 cm) [21% (7-34%) of the initial length] could be
achieved with a healing rate of 1.3 mo/cm and a complication rate of 40%. The
ulna-group (n=3) reached an average lengthening of 2.6 cm (2.2-3.4 cm) [21% (17
24%) or the initial length] with a healing index of 1.4 mo/cm and a complication
rate of 17%. The knee contracture group (n=2) was free of complications. The
Ilizarov technique has been performed successfully in a high percentage although
extensive elongations reported by Ilizarov could not be achieved neither by us
nor by other authors. The above-mentioned method has been proved to be efficient
and successful to correct deformities of the soft-tissue.
PMID- 9654692
TI - [Coping with anger and the premenstrual syndrome].
AB - OBJECTIVE: Investigations in recent years confirm the importance of "anger coping
behaviour" for women suffering from different diseases such as migraine, high
blood pressure and coronary heart disease. The hypothesis for this investigation
was that "anger-in" coping (anger-suppression) is a possible causal factor in the
premenstrual syndrome. METHODS: Data analysis was undertaken on 38 patients
(average age 32 years) fulfilling the inclusion criteria. The Menstrual Distress
Questionnaire (MDQ) was used for measuring the intensity of premenstrual
symptoms. As a result of a cluster analysis of MDQ scores, the 38 patients were
divided into 3 subgroups (group 1: mild symptoms, n = 16; group 2: moderate
symptoms, n = 10; groups 3: severe symptoms, n = 12). The 3 groups were compared
by using different questionnaires regarding the variables anger, attitudes to
menarche and menstrual bleeding, anxiety and depression. Additionally,
sociodemographic data were obtained and a daily record taken for 2 days
premenstrually and 5 day postmenstrually of subjective replies to a standardized
protocol. RESULTS: Contrary to our expectations the results showed no significant
differences for "anger coping" between the 3 subgroups. Increased daily stress
(professional and familial double load) statistically significantly influenced
the intensity of premenstrual symptoms. Additional significant factors were a
general tendency towards somatization disorder, a negative attitude toward
menarche and menstrual bleeding, as well as a tendency to depressive mood in
patients with severe premenstrual symptoms. CONCLUSION: Emotional disorders
(anger, anxiety) showed less influence on the premenstrual syndrome in the
investigated women than daily stress and medical anamnesis.
PMID- 9654693
TI - Adverse events after oral vaccination against cholera with CVD103-HgR.
AB - The goal of the present study was to evaluate the tolerability and acceptability
of an oral cholera vaccine (CVD103HgR) in individuals preparing for travel to
countries endemic for cholera. 2545 Austrian travelers between 6 months and 81.5
years of age received a single dose of CVD103HgR and were asked to complete a
questionnaire for documentation of adverse events during a 7 day period post
immunization. Events were recorded regardless of whether they were caused by
concomitant vaccinations or other factors and thus, a causative relationship was
not necessarily present. Despite this drawback and the possibility of
overreporting this study has proven a low frequency in side effects and the good
tolerability of CVD103HgR. Occasional gastrointestinal side effects (15%
diarrhea, 8.1% nausea, 1.1% vomiting) were seen and were of mild character and
probably a consequence of associated intake of sodium bicarbonate buffer. Other
events (7% skin eruptions, 2.7% fever) were mild and considered as harmless (or
not vaccine related). The results show that the oral cholera vaccine CVD103HgR
was well tolerated and accepted by travelers.
PMID- 9654694
TI - Aldosterone-producing adenoma associated with foci of myelolipoma.
AB - The simultaneous occurrence of adrenal myelolipoma and endocrine disorders is
rare. Myelolipomas have occasionally been found in patients with Cushing's
syndrome, pheochromocytoma and hyperthyroidism. A recently published study
described one well-documented case of adrenal adenoma and myelolipoma in a
patient with Conn's syndrome. In this report the patient had a one-year history
of treated hyperthyroidism and diagnosed aldosterone-producing adenoma. A
disseminated adrenal myelolipoma was found within the adrenocortical adenoma. To
our knowledge this histological finding has not been previously reported in
association with both Conn's syndrome and hyperthyroidism.
PMID- 9654696
TI - [New aspects of the pathophysiology of heart failure].
AB - The progression of heart failure is related to activation of neuroendocrine
hormone systems. On the level of the myocardium, they contribute to hypertrophy,
dilation and remodeling of the ventricles. In addition, vascular alterations with
endothelial dysfunction and alterations of skeletal muscle contribute to clinical
symptoms of heart failure patients. Changes in ventricular geometry during the
progression of cardiac diseases are associated with specific subcellular
alterations on the level of the myocytes. Especially, disturbed intracellular
Ca2+ handling resulting in altered excitation contraction coupling may lead to
impaired systolic and diastolic function. Disturbed Ca2+ homeostasis has been
associated with reduced re-uptake capacity of the sarcoplasmic reticulum for Ca2+
and an enhanced activity of the sarcolemmal Na+/Ca2+ exchange. In consequence,
alterations in force-frequency behavior were attributed to a decline in
intracellular Ca2+ transients at higher stimulation rates. The reduced expression
of myocardial beta-adrenoceptors and alterations on the level of the G-proteins
result in a reduced activity of adenylate cyclase and reduction in intracellular
cAMP content of the myocytes. In consequence, reduced phosphorylation of
intracellular functional proteins in the failing human heart contributes to
altered Ca2+ handling. The Frank-Starling-mechanism seems to be unaltered in
failing isolated human myocardium. Endothelin and angiotensin may contribute to
the regulation of myocardial contractility in the human heart, but their
functional relevance in the regulation of myocardial contractility under clinical
conditions remains to be evaluated.
PMID- 9654697
TI - [Significance of neuroendocrine parameters in heart failure].
AB - Heart failure is defined as a malfunction of the cardiac muscle. The ongoing
interaction between pump failure and the vasculature, however, results in
symptoms due to malperfusion of the pulmonary and systemic circuit. As a
consequence, biologic systems of pressure and volume control are activated. In
the neurohumoral heart failure model the sympathetic nervous system, the renin
system and endothelin all develop their own pathologic contribution to the
disease process. Thereby the role of endothelin seems to be special since its
production is particularly increased in advanced disease. Like angiotensin,
endothelin has major proliferative properties to promote adverse vascular and
myocardial growth. The finding of increasing neurohumoral activation as heart
failure progresses and the role of plasma levels of neurohormones as predictors
of mortality has rearranged the primary goal of therapy to suppress these
deleterious neurohumoral systems as completely as possible. Though angiotensin
converting enzyme inhibitors are currently first line therapy of heart failure,
uncertainties remain concerning their mechanisms of action and - associated to
that - optimal dosing.
PMID- 9654698
TI - [Diagnosis of heart failure].
AB - Heart failure is a clinical syndrome caused by various etiologic factors. The
physician should undertake every effort to identify potentially reversible causes
that lead to heart failure. Therefore one should go through various non-invasive
as well as invasive diagnostic procedures. The diagnostic tests can be helpful in
identifying patients with a poor prognosis.
PMID- 9654699
TI - [Drug therapy of chronic heart failure].
AB - Prevention of disease leading to cardiac dysfunction, improvement of quality of
life and reduction of mortality are the primary objectives in the treatment of
chronic heart failure. The therapeutic possibilities are various, including
general advices, pharmacological therapy and surgical interventions. Standard
medical treatment of systolic cardiac dysfunction contains ACE inhibitors,
diuretics and cardiac glycosides. Beta-blocking agents, oral anticoagulation and
antiarhythmic drugs can be used in addition. A therapeutic management of chronic
heart failure tailored to the individual patient has nowadays become available
due to multiple treatment options.
PMID- 9654700
TI - [Pacemaker therapy in heart failure].
AB - Drug therapy is the standard therapy for heart failure. The current state of the
art does not permit pacemaker therapy as a general recommendation for left
ventricular failure. Numerous controversial reports have been published on the
success of pacemaker therapies for congestive heart failure. Iskandrian reported
on tachycardiac atrial stimulation in 1986. Since 1990 several papers have been
published on DDD-pacemakers with short AV-time. From the data available to us,
congestive heart failure is generally not considered a new pacemaker indication.
In carefully selected patients, however, an improvement in hemodynamics as well
as in NYHA-classification can be expected, both in acute cases and on a long-term
basis. In 16 patients Hochleitner demonstrated a significant increase in left
ventricular ejection fraction, a significant drop in NYHA-classification, heart
size and an increase in systolic and diastolic blood pressure. Using
echocardiography Brecker showed a decrease in mitral regurgitation, an increase
in ventricular filling time and, by means of ergometry, a major increase in
cardiac output. The hypothesis for the working mechanism is that a shorter AV
time optimizes the time needed for AV-contraction, thereby reducing mitral
regurgitation, lengthening ventricular filling time and thus increasing ejection
fraction. Identification of the patients to whom this hypothesis can be applied
is difficult but imperative. The optimal AV-time for each patient must be
established on an individual basis using echocardiography, Doppler sonography and
ergometry and must be finetuned in follow-up controls. Optimization of AV-time in
patients with the classic indications for a pacemaker as well as a combination of
cardioverters and DDD-pacemakers should be aimed for in patients with congestive
heart failure and high NYHA-classification.
PMID- 9654701
TI - [Mechanical circulatory support in heart failure].
AB - Heart transplantation is an established therapy for end-stage cardiac disease.
The number of organ donors is limited, and the mortality on the waiting list is
increasing. To give these patients a chance to survive their waiting time,
chronic mechanical circulatory support, especially left ventricular assist
devices have been clinically established. The results with this therapy are
encouraging. Because of these results trials using these devices as an
alternative for cardiac transplantation are initiated. Due to the further
development and miniaturization of such devices this indication will become more
important. The most interesting patients are the one, in which devices could be
explanted after chronic support, because their myocard has recovered. If we can
find a way to identify such patients a new form of therapy for end-stage heart
disease could be established.
PMID- 9654702
TI - [Guidelines for therapy of chronic pancreatitis. Consensus Conference of the
German Society of Digestive and Metabolic Diseases. Halle 21-23 November 1996].
PMID- 9654704
TI - Experiences with novel techniques for reduction of stent flow in transjugular
intrahepatic portosystemic shunts.
AB - The transjugular intrahepatic portosystemic shunt (TIPS) may deteriorate liver
function and can cause encephalopathy in patients with cirrhosis of the liver.
Then reduction of TIPS flow may be required. We here report several attempts to
reduce shunt flow in TIPS-induced encephalopathy or liver function impairment
with novel techniques. Three patients with cirrhosis of the liver were
investigated: Two with severe recurrent encephalopathy and one with impaired
liver function following TIPS insertion. Insertion of a reducing stent was
ineffective to decrease shunt flow velocity in one patient with severe
coagulopathy. Sufficient reduction of shunt flow was achieved by embolizing the
space around the hourglass waist of the reducing stent with an occlusion
emulsion. Insertion of a conventional stent within the preexisting TIPS with or
without additional embolization reduced TIPS flow in the other patients. After
reduction of shunt flow encephalopathy improved and liver function returned to
the level before TIPS, respectively. During follow-up no occlusion of TIPS was
observed. Thus, reduction of shunt flow velocity can be achieved by insertion of
an additional stent into a curve-shaped TIPS. Embolization can be helpful to
decrease TIPS flow, particularly in patients with severe coagulopathy. Reduction
of TIPS flow can correct TIPS-induced complications.
PMID- 9654703
TI - [Is chronic laryngitis associated with Helicobacter pylori? Results of a
prospective study].
AB - H. pylori is found in the stomach of patients with chronic gastritis. The
infection is usually transmitted by the gastro-oral route and bacteria could be
identified in saliva and dental plaque. An essential cause of chronic laryngitis
is gastroesophageal reflux. The aim of the study was to evaluate if a H.pylori
associated chronic laryngitis exists. 38 patients with chronic laryngitis
underwent gastroscopy. Biopsies were taken from the gastric antrum and body,
lower, middle and upper esophagus. H. pylori was diagnosed by rapid urease test
and histology. 14 of the patients (36.8%) were H.pylori-positive, but the
bacteria could not be identified between stomach and larynx. 24 patients were H.
pylori-negative. Seven patients (18.4%) suffered from esophagitis, six of these
patients were H. pylori-negative. The H. pylori-infected patients received triple
therapy for one week, in case of esophogitis Omeprazole 20 mg BID was prescribed.
Six weeks later a follow-up endoscopy was performed. The eradication rate was
12/14 (85.7%), in all patients with reflux the esophagitis was cured. The
laryngitis was clinically and endoscopically unchanged in ten of the twelve
(83.3%) patients after successful treatment for H. pylori; in the remaining two
patients as well as in the two H. pylori-positive patients the laryngitis was
improved. In six out of the seven patients with esophagitis the laryngitis had
healed completely and was improved in the remaining patient. It may be concluded
that there is no evidence for the existence of H. pylori-associated laryngitis,
suggesting that acid reflux is the underlying etiology.
PMID- 9654706
TI - [Diclofenac-associated acute cholestatis hepatitis].
AB - Diclofenac is an anti-inflammatory analgesic which is widely used in the therapy
of inflammatory joint pain. Diclofenac hepatotoxicity ranges from asymptomatic
elevation of transaminase activity to significant liver disease. 31 cases of
diclofenac-induced hepatitis with five associated deaths have been already
reported in the English, French and Spanish literature. We report the case of a
64-year-old patient who was admitted to the hospital with an icteric hepatitis of
sudden onset. The only drug that was taken before admission was diclofenac in a
daily dose of 150-200 mg because of a spondylodiscitis. Work-up of the patient
included ERCP, laparoscopy and liver biopsy and excluded other reasons of a
cholestatic hepatitis. Discontinuation of diclofenac resulted in normalization of
transaminase activity and bilirubin concentration within four months. The
frequent use of diclofenac and the possibility of fatal liver damage highlights
the need that diclofenac-toxicity should be considered in the differential
diagnosis of acute cholestatic hepatitis.
PMID- 9654705
TI - [Follow-up of benign recurrent intrahepatic cholestasis (Summerskill-Walshe
Tygstrup syndrome) over 46 years].
AB - Benign recurrent intrahepatic cholestasis (BRIC or Summerskill-Walshe-Tygstrup
syndrome) is a rare autosomal recessive form of liver disease, which usually
becomes manifest in childhood. Characteristic are recurrent episodes of jaundice
and itching of different duration. Number and duration of episodic attack and
asymptomatic period develop individually. For diagnosis of BRIC following
criteria are proposed: At least three episodes of severe jaundice and pruritus
with biochemical evidence of cholestasis, normal intra-and extrahepatic bile
ducts on cholangiography, absence of a factor known to produce intrahepatic
cholestasis and symptom-free intervals of several months or years. Often the
diagnosis of BRIC is made very late and patients have to suffer invasive
investigations (explorative laparotomy). Because of the unknown
pathophysiological mechanism there is no specific treatment. We report on a 53
year-old patient with jaundice, severe pruritus, vomiting, loss of hair and
weight, extreme sleeplessness and intractable cough. At the onset of the attack
an increase of serum bilirubin concentration and serum alkaline phosphatase was
observed, whereas aspartate and alanine aminotransferase and gamma
glutamyltransferase were normal. Histological findings of liver biopsy revealed
accumulation of bile plugs in bile canaliculi. The long-term follow-up of our
patient confirms that the prognosis is good.
PMID- 9654707
TI - [Cryoglobulinemia and chronic liver diseases].
AB - Cryoglobulinemia can be associated with several infections, immunoproliferative
tumors, chronic liver, renal and systemic autoimmune diseases. In the first part
of the publication the authors give a review of the main clinical and laboratory
properties of cryoglobulins. In essential mixed cryoglobulinemia syndrome
(purpura, arthralgia, weakness) clinical and laboratory signs of damaged liver
function can often be seen. However, there are mixed cryoglobulins in chronic
liver disease of different etiologies as well. In 30-94% of patients with
hepatitis C virus infection and hepatitis C virus-induced chronic liver diseases
laboratory signs (occasionally clinical symptoms as well) or mixed
cryoglobulinemia can be diagnosed. Serological markers of hepatitis C virus
infection have been found in the cryoprecipitates of patients with mixed
cryoglobulinemia. A high prevalence of mixed cryoglobulins in serum of patients
with chronic hepatitis C virus infection and hepatitis C virus-induced chronic
liver disease suggests that this virus has a significant role in the pathogenesis
of mixed cryoglobulins. Also, an impaired clearance function of the liver in the
uptake of cryo(immuno)complexes may be an important causative factor in the
production of cryoglobulins in chronic liver diseases of different etiologies.
PMID- 9654708
TI - [Prevention and early detection of colorectal carcinoma by endoscopic
examinations].
AB - People at average risk for colorectal cancer (asymptomatic, age > or = 45 years,
no risk factors) are offered fecal occult blood testing each year and
sigmoidoscopy every five years. In case of a positive fecal occult blood test,
examination of the whole colon by colonoscopy should be performed. Colorectal
cancer risk is significantly lowered by endoscopic polypectomy in patients with
adenomas. After complete removal of adenomatous polyps a control colonoscopy is
advised three years after the initial examination. People with a positive family
history of colorectal cancer or adenomatous polyps, of inherited polyposis
syndromes, of a hereditary non-polyposis colorectal cancer, after polypectomy,
after resection of colorectal cancer and with inflammatory bowel disease possess
an increased risk for the development of colorectal cancer. Surveillance
recommendations in these cases are detailed. In order to increase the cost
benefit ratio in surveillance after curative resection of colorectal cancer the
frequency of the surveillance procedures can be reduced. In patients with total
or extensive ulcerative colitis colonoscopy with multiple biopsies should be
performed after a disease duration of eight to ten years, further recommendations
depend on the histopathologic results.
PMID- 9654709
TI - [Laparoscopic resection in comparison with open resection of adenocarcinoma of
the colon].
PMID- 9654710
TI - [Ethical guidelines for performing percutaneous endoscopic gastrostomy (PEG
catheter)].
PMID- 9654711
TI - [Prognostic value of immunohistochemically identifiable tumor cells in lymph
nodes of patients with RO-resected esophageal carcinoma].
PMID- 9654712
TI - [Fetal pulse oximetry].
PMID- 9654713
TI - [Placentation in the human: a transplantation or tumor model?].
AB - In human placentation, anchoring villi develop to attach the placenta to the wall
of the uterus. This attachment is brought about by extensive infiltration of the
maternal tissue by cytotrophoblast cells of fetal origin. As trophoblast cells do
not express classical histocompatibility antigens (HLA antigens), increasing
doubt has been cast upon the "transplantation" model of pregnancy. However, more
recently discovered, previously unknown HLA antigens on the invasive
cytotrophoblast cells could lead to maternal immune responses similar to those
observed following organ transplantation. Nevertheless, the biological behaviour
of the invasive cytotrophoblast cells suggests more parallels with the processes
of invasion and metastasis seen in malignant tumours, although there is
regulation of the timing and extent of cytotrophoblast invasion of the uterus in
normal pregnancy. In this survey, findings relating to the control of
infiltration by the cytotrophoblast are reviewed, with particular reference to
immunology and tumour biology. Possible effects on pregnancy and parturition due
to failure of the regulatory processes involved in placentation are discussed.
PMID- 9654714
TI - [Single intrauterine fetal death in twin pregnancy].
AB - During a 11 year period (1984-1994) we identified and analysed at the Department
of Obstetrics, University Hospital of Zurich, among 541 twin pregnancies 19 with
single intrauterine death (SIUD) in the second and third trimester. The preterm
delivery rate was 68% and much higher compared to singleton pregnancies at the
same institution (17%). The caesarean section rate was 47% and also higher
compared to singleton pregnancies (21%) but lower than in a normal twin
collective (61%). Two of the surviving twins showed malformations. One of them
has in addition of porencephaly, probably due to disruption syndrome. In 12 out
of 19 case a monochorionic placenta was found including 5 with twin-twin
transfusion syndrome. Surprisingly 8 out of 19 dead fetuses had a velamentous
insertion of the umbilical cord. This might suggest a causal relationship to
SIUD. 95% showed the same sex. Maternal blood coagulation disorders are rare.
From our results we conclude that SIUD is associated with an increased preterm
delivery and caesarean section rate. Monochorionic twins and twins with
concordant sex demonstrate the highest risk for SIUD. The twin-twin transfusion
syndrome is the main single cause for SIUD. The pathophysiologic role of
velamentous insertion remains unclear.
PMID- 9654715
TI - [Erythropoietin and obstetric factors--evaluation with special reference to sex
differences].
AB - OBJECTIVE: We evaluated fetal Erythropoietin (EPO) in a clinical obstetrical
environment, aiming to collect more information upon its role in diagnosis of
fetal stress. As it is known that EPO cannot pass the placental barrier, we
restricted to measure the concentration in the umbilical artery (UA) immediately
after delivery. PATIENTS AND METHODS: EPO was correlated to relevant obstetrical
parameters. We looked for each parameter that was tested for differences in fetal
sex. For this purpose, the statistics were performed by means of the Behrens
Fisher-Test (meaning a special application of the Student-T-Test). This device is
an algorithm developed to compare regressions. For significance, a confidence
level of less 5% was accepted. For the rest, we only used descriptive devices.
RESULTS: We found weak but positive correlation to gestational age for both
sexes. No correlation was calculated for the duration of parturition or the birth
weight. Highly significant differences were found for respiratory values of blood
gases, taken from the UA when differentiated for fetal sex: males showed a strong
and negative correlation for pO2 (r(m)= -0.45); the female EPO-level was not
influenced by decreasing O2-level (r(w)= +0.06, p > 0.01). Similar results could
be found for pCO2. (r(m)= +0.36; r(w)= -0.07; p < 0.01. Not significant, but
comparable differences for the EPO-level in fetal blood were found for pH and
base deficit. CONCLUSIONS: If we accept that the EPO-level in fetal blood rises
with relevant oxygen deficiency, then females seems to be better protected
against damage from distress. This observation is congruent with the clinical
experience from the authors who have the subjective impression that female sex is
advantageous in harmful deliveries.
PMID- 9654716
TI - [Kinetocardiotocography--KCTG--during pregnancy in an ambulatory care patient
sample and in hospitalized patients with special reference to tocolysis].
AB - With kinetocardiotocography (KCTG), fetal movements can be registered parallel to
the fetal heart rate. Hewlett Packard equipment of the series 1350 A allows the
movements to be registered an quantified on the CTG paper. In this study,
hospitalized pregnant women > 26 gestational weeks (GW) on i.v. tocolysis, and
out-patients > 34 GW at the out patient department were examined with KCTG and
the results compared. A wide distribution of fetal activity was seen in both
groups. With advancing pregnancy, the number of fetal movements as well as the
duration of activity per time unit decreased, whereas the length of time of
individual movements slightly increased, in both groups. No statistically
significant difference was seen between different gestational ages nor between
the two groups. KCTG is being increasingly used to monitor the fetal condition,
especially for risk pregnancies. It can provide additional information in the
form of a biophysical variable.
PMID- 9654717
TI - [Monstrous fetal lymphangioma of the thoracic wall bilaterally. Case report and
discussion of diagnosis and perinatal management].
AB - Prenatal diagnosis, perinatal management, and surgical treatment of children with
lymphangioma can cause considerable difficulties. This paper presents a case of a
thoracic wall lymphangioma diagnosed in the seventeenth week of pregnancy, with
quickly developed monstrous dimensions. The postnatal phase was complicated by
preterm delivery in the 32nd week or pregnancy, bleeding in the tumor and
mechanical compression of the thorax by the huge masses. Pediatric intensive care
and surgical treatment save the child. Cosmetic result is convenient. By example
of the presented case the literature, problems of diagnosis, perinatal management
and nomenclature of lymphangioma are discussed.
PMID- 9654718
TI - [Wilson disease and pregnancy. Review of the literature and case report].
AB - Wilson's disease is an autosomal recessive disorder of copper metabolism. Since
the introduction of penicillamine treatment successful pregnancies have been
reported. However little is known about the risks of breast feeding in patients
on this medication. We describe the case of a patient suffering from Wilson's
disease, who had two uncomplicated pregnancies and breast fed both children for a
period of three months each. In the 22 year old gravida I para I the diagnosis of
Wilson's disease had been previously made by liver biopsy and penicillamine
therapy had been begun. At the time of her first presentation at our department
she was 8 week pregnant. Her renal and liver function were normal. Neurologic or
psychiatric symptoms were not observed. At 18 weeks the dosage of penicillamine
was reduced from 900 mg/d to 750 mg/d. The course of the pregnancy remained
uneventful. At 38 + 1 weeks a healthy boy of 3100 gm was delivered. 19 months
later the patient presented again in the 16th week of her second pregnancy.
Concerning Wilson's disease no major changes were observed, especially liver and
renal function were not impaired. The dosage of penicillamin was reduced from 900
mg/d to 750 mg/d during the 21st week. The pregnancy again was uncomplicated and
at 38 + 2 weeks resulted in the spontaneous deliver of a healthy boy, weighting
3940 gm. Both children were breast fed over a period of three months and with the
exception of an icterus prolongatus no adverse effects were noted.
PMID- 9654719
TI - [Monozygotic multiple pregnancies with acardiac anomalies].
AB - The acardiac fetus is a rare anomaly of about 1 percent of monozygotic
pregnancies, occurring in approximately 1 in 35,000 pregnancies. The special
hemodynamic circumstances of the normal heart having to pump an excessive amount
of blood for a long period of time will influence the chance of survival of this
fetus. In two case-report with many figures pathologic-anatomical problems and
prospective management to improve the outcome of monozygotic multiple pregnancies
complicated by acardiac malformation were presented. The pathogenesis of
metabolic dysbalance in these pregnancies was discussed.
PMID- 9654720
TI - [An unusual course of fetal gastroschisis].
AB - We report on prenatal diagnosis of gastroschisis at 20th gestational week. In
addition to gastroschisis intraabdominal intestinal stenosis was detected. As a
consequence cesarean section was planned close to term. Control examinations in
the last trimester didn't confirm initial diagnosis so that the recommended mode
of delivery was changed. However postpartum diagnosis again confirmed the early
diagnosis of gastroschisis including spontaneous necrosis of dislocated
intraamniotic intestinal parts. The course demonstrates that even at unambiguous
prenatal diagnosis control examinations are recommended as dynamic changes may
occur in the second and third trimester. Thus mode of delivery may have to be
adapted close to term to reduce maternal risk.
PMID- 9654721
TI - [Don't wait until the press discovers you].
PMID- 9654722
TI - [Myopia or retinal detachment in the obstetric clinic].
PMID- 9654723
TI - [Obstetrical management in enucleated myoma].
PMID- 9654724
TI - [30 years specialist for pediatric and adolescent psychiatry and psychotherapy].
PMID- 9654725
TI - [Incidence of psychiatric symptoms and somatic complaints in 4- to 10-year-old
children in Germany as judged by parents--a comparison of norm-oriented and
criteria-oriented models].
AB - OBJECTIVES: To analyze the frequency of behavioral/emotional problems and somatic
complaints of children aged four to ten as rated by their parents. METHOD: The
analysis is based on the PAK-KID study on behavioural and emotional problems and
psychosocial competencies of children and adolescents in Germany. In a nationally
representative sample of N = 1030 children aged four to ten years the parents
rated their child using the Child Behavior Checklist. RESULTS: The prevalence
rates of the symptoms are presented. Additionally global prevalence rates based
on three different models were calculated and compared. They range from 13.1% to
28.3%. The issues of defining cutoffs necessary for the calculation of prevalence
rates are discussed.
PMID- 9654726
TI - [Variability of inpatient child and adolescent psychiatry--results of a
multicenter documentation].
AB - OBJECTIVE: For the first time in the German-speaking countries a complete
evaluation of all 1236 inpatient treatment episodes within one year of
investigation was carried out. METHOD: Case-related patient documentation at all
of the 13 clinics for child and adolescent psychiatry in Lower Saxony and Bremen
were evaluated. RESULTS: Data from all clinics agreed widely on the following: 1.
the divergent family structures of the young patients compared to those of the
general public, 2. a high degree of individual psychotherapy, and 3. the
inclusion of the patient's social circumstances in the individual psychotherapy.
Nonetheless, results for most of the variables assessed differed strongly.
Inpatient child and adolescent psychiatric care thus seems to vary highly among
clinics within the same epidemiological area. CONCLUSIONS: Hence, even when the
reported number of episodes is high, no general conclusions on inpatient child
and juvenile psychiatric treatment can be drawn on the basis of admissions data
for individual clinics. Interinstitutional comparisons must be made on the
assumption that there is no prototype clinic for child and adolescent psychiatry.
Additional general conclusions include the lack of a disorder-specific approach
to treatment. The entry of a large number of patients into foster or state homes
following inpatient treatment reflects the impact upon them of abnormal
psychosocial circumstances, as well as their decreased psychosocial adaption.
PMID- 9654727
TI - [Comparison of 2 clinics with reference to axis 5 of the MAS: different patient
populations or regional characteristics?].
AB - OBJECTIVE: The university departments of child psychiatry in Cologne and Berlin
were compared to assess whether quantitative differences in reported abnormal
psychosocial situations (Axis 5 MAS of ICD-10) are due to a difference in patient
population or coding practices or to particular regional conditions. METHOD: Data
were analyzed for 593 patients seen in Cologne in 1992/93 and for 685 patients
seen in Berlin in the same period. The broader social situation was described by
sociodemographic data from the respective city. RESULTS: Berlin showed about
twice as many psychosocial stressors per patient as Cologne. Consistent
relationships between axis 5 stress ratings and other parameters indicated the
validity of the data. Only a few points of inconsistency in the data were found.
The sociodemographic data for both cities revealed a greater number of single
parents as well a a higher rate of suicide in Berlin. CONCLUSIONS: Indicators for
the validity of the clinical data analyzed were found. Some special internal
clinical and regional conditions were identified as contributing to the
quantitative differences between the two university departments.
PMID- 9654728
TI - [Effects and significance of specific spelling problems in young adults-
empirical studies in an epidemiologic patient sample].
AB - OBJECTIVE: With reference to an epidemiological sample of adolescents and young
adults the impact of different models on the number of children classified as
having specific spelling problems is investigated. METHOD: Using the same set of
data, the effect of alternative definitions and methodological procedures on the
prevalence of specific spelling retardation is shown. The virtual consequences of
various norm-orientated definitions of cases is discussed with reference to
external empirical criteria. RESULTS: Particularly, obsolete norms lead to a
large overestimation of cases. In the present study case definitions of specific
spelling retardation based on substantial criteria result in prevalence rates
between 6 and 9 percent. Academic achievement is considerably affected by
persisting specific spelling problems and the attendance of secondary schools is
rare, in spite of sufficient nonverbal intelligence. CONCLUSIONS: Because of the
high impact of spelling ability for educational success, dyslexic children need
help by early intervention. Furthermore scholastic promotion is necessary to
enable a school carer appropriate to the intellectual possibilities of the child.
PMID- 9654729
TI - [Differences in the spontaneous organization of auditory verbal learning in brain
damaged adolescents].
AB - OBJECTIVE: Subjective organization (SO) of verbal memory and learning was
investigated for 44 adolescent patients. METHOD: The patients were subdivided
into four clinical groups according to localization of lesion: right hemisphere
(RH), left hemisphere (LH), frontal (FL), and brain stem (SL). RESULTS: As
expected RH patients performed best on this verbal learning task, whereas FL and
SL patients demonstrated very poor SO, indicating their failure in categorize
memory input. LH patients increased SO, following successive trials, which
suggests an active learning strategy. CONCLUSIONS: It is argued that the use SO
analysis in neuropsychology will stimulate the course of further research towards
attaining a better understanding of memory and learning impairments and their
remission in brain-damaged patient.
PMID- 9654730
TI - Renal impairment in hepatic cryotherapy.
AB - Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following
cryotherapy, and its etiology is unknown. The aim of this study was to assess the
impact of hepatic cryotherapy on renal function, and whether this effect is
related to volume of cryotherapy, and to identify any predictors of renal
impairment in patients who undergo cryotherapy. A retrospective analysis of all
patients with primary or secondary hepatic malignancy treated with cryotherapy
from April 1990 to October 1996 was conducted. Ten of 204 patients with renal
impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2
days postprocedure) were identified. One patient has postoperative pancreatitis
with late renal impairment (20 days) and was excluded. The severity of renal
impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19).
Two patients required temporary hemodialysis. Only one patient, who had
significant cardiac disease, had associated pulmonary injury and shock.
Demographic data in both groups were comparable, except for a trend toward more
noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194).
Patients in the renal impairment group had a greater number of lesions than those
of the nonrenal impairment group (3.4 vs 2.1, p < 0.01), as well as larger lesion
diameter (2.9 vs 1.9, p < 0.01), increased freezing time (74.7 vs 44.3, p <
0.01), and a higher aspartate transaminase (AST) (2254 vs 1157, p < 0.01). This
study suggests that renal impairment is more likely to be seen in patients
undergoing more extensive cryotherapy. The number and diameter of lesions
together with AST data link renal injury with magnitude of liver injury--all
renal impairment patients had an AST > 1000, compared with only 28% of patients
who did not.
PMID- 9654731
TI - Cytosolic pH variations in perfused rat liver at 4 degrees C: role of
intracellular buffering power.
AB - The effect of low temperature on cytosolic pH regulation and buffering capacity
was evaluated in the isolated rat liver. The pH changes were followed by
phosphorus-31 nuclear magnetic resonance. Cooling from 37 to 4 degrees C, with
Krebs-Heinseleit perfusion at an external pH of 7.35, induced an alkaline shift
in cytosolic pH (pHcyt) of 0.13 or 0.75 pH units in the presence of bicarbonate,
respectively (dpH cys/dT values were 0.004 and 0.022 unit/degrees C. With 4
degrees C perfusion, in the presence or absence of bicarbonate, acute changes of
external pH (from 7.40 to 5.90) did not affect pHcyt. In contrast, intracellular
loading with isobutyric acid or NH4Cl induced rapid pHcyt variations. The
intrinsic buffering power value (10 to 50 slykes) measured in the absence of
bicarbonate depended on pHcyt. The larger value was observed for pHcyt 7.30, a
value near the pK value of the imidazole group of intracellular proteins at 4
degrees C. The presence of bicarbonate modified the amplitude of the pHcyt change
by increasing the total buffering power. It was demonstrated that during
hypothermia, ionic carriers are inactivated and the charged forms of molecules
are unable to cross the cell membrane; thus, the pHcyt homeostasis depends
essentially on intracellular buffering power.
PMID- 9654733
TI - Membrane permeability characteristics of metaphase II mouse oocytes at various
temperatures in the presence of Me2SO.
AB - In this study, the hydraulic conductivity (Lp), Me2SO permeability (PMe2SO), and
the reflection coefficients (sigma) and their activation energies were determined
for Metaphase II (MII) mouse oocytes by exposing them to 1.5 M Me2SO at
temperatures of 30, 20, 10, 3, 0, and -3 degrees C. These data were then used to
calculate the intracellular concentration of Me2SO at given temperatures.
Individual oocytes were immobilized using a holding pipette in 5 microliters of
an isosmotic PBS solution and perfused with precooled or prewarmed 1.5 M Me2SO
solutions. Oocyte images were video recorded. The cell volume changes were
calculated from the measurement of the diameter of the oocytes, assuming a
spherical shape. The initial volume of the oocytes in the isoosmotic solution was
considered 100%, and relative changes in the volume of the oocytes after exposure
to the Me2SO were plotted against time. Mean (means +/- SEM) Lp values in the
presence of Me2SO were (LpMe2SO) at 30, 20, 10, 3, 0 and -3 degrees C were
determined to be 1.07 +/- 0.03, 0.40 +/- 0.02, 0.18 +/- 0.01, 7.60 x 10(-2) +/-
0.60 x 10(-2), 5.29 x 10(-2) +/- 0.40 x 10(-2), and 3.69 x 10(-2) +/- 0.30 x 10(
2) microns/min/atm, respectively. The PMe2SO values were 3.69 x 10(-3) +/- 0.3 x
10(-3), 1.07 x 10(-3) +/- 0.1 x 10(-3), 2.75 x 10(-4), +/- 0.15 x 10(-4), 7.83 x
10(-5) +/- 0.50 x 10(-5), 5.24 x 10(-5) +/- 0.50 x 10(-5), and 3.69 x 10(-5) +/-
0.40 x 10(-5) cm/min, respectively. The sigma values were 0.70 +/- 0.03, 0.77 +/-
0.04, 0.81 +/- 0.06, 0.91 +/- 0.05, 0.97 +/- 0.03, and 1 +/- 0.04, respectively.
The estimated activation energies (Ea) for LpMe2SO, and PMe2SO, and sigma were
16.39, 23.24, and -1.75 Kcal/mol, respectively. These data may provide the
fundamental basis for the development of more optimal cryopreservation protocols
for MII mouse oocytes.
PMID- 9654735
TI - Temperature threshold and preservation of signaling for mitochondrial membrane
proteins during ischemia in rabbit heart.
AB - Temperature modulates both myocardial energy requirements and production. We have
previously demonstrated that myocardial protection induced by hypothermic
adaptation preserves expression of genes regulating heat shock protein and the
nuclear-encoded mitochondrial proteins, the adenine nucleotide translocator
isoform 1 (ANT1), and the beta subunit of F1-ATPase (beta F1-ATPase). This
preservation is associated with a reduction in ATP depletion similar to that
noted in cardioplegic arrested hearts preserved at a critical temperature (30
degrees C) or below. We tested the hypothesis that expression of these genes may
also be subject to this temperature threshold phenomenon. Isolated perfused
rabbit hearts were subjected to ischemic cardioplegic arrest at 4, 30, or 34
degrees C for 120 min. Cardiac function indices and steady-state mRNA levels for
ANT1, beta F1-ATPase, and HSP70-1 were measured prior to ischemia (B) and after
45 min of reperfusion. Cardiac function was significantly depressed in the 34
degrees C group. Ischemia at 34 degrees C reduced steady-state mRNA levels for
ANT1 and beta F1-ATPase from B, but these levels were similarly preserved at 4
and 30 degrees C. HSP70-1 levels were mildly elevated (fourfold) above B to
similar levels at all three temperatures. These results indicate that mRNA
expression for ANT1 and beta F1-ATPase is specifically preserved in a pattern
consistent with the temperature threshold phenomenon. HSP70-1 expression is not
influenced by ischemic temperature. Preservation of gene expression for these
mitochondrial proteins implies that signaling for mitochondrial biogenesis or
resynthesis is maintained after ischemic insult.
PMID- 9654736
TI - Evolution of repetitive proteins: spider silks from Nephila clavipes
(Tetragnathidae) and Araneus bicentenarius (Araneidae).
AB - Spider silks are highly repetitive proteins, characterized by regions of
polyalanine and glycine-rich repeating units. We have obtained two variants of
the Spidroin 1 (NCF-1) silk gene sequence from Nephila clavipes. One sequence
(1726 bp) was from a cloned cDNA, and the other (1951 bp) was from PCR of genomic
DNA. When these sequences are compared with each other and the previously
published Spidroin 1 sequence, there are differences due to sequence
rearrangements, as well as single base substitutions. These variations are
similar to those that have been reported from other highly repetitive genes, and
probably represent the results of unequal cross-overs. We have also obtained 708
bp of sequence from pCR of genomic DNA from Araneus biocentenarius. This sequence
shows considerable similarity to a dragline sequence (ADF-3) from A. diadematus,
as well as Spidroin 2 (NCF-2) from N. clavipes. Minor but consistent differences
in the repeating unit sequence between A. bicentenarius and A. diadematus suggest
that concerted evolution or gene conversion processes are acting to maintain
similarity among repeat units within a single gene.
PMID- 9654737
TI - Identification of proteins and developmental expression of RNAs encoded by the
65A cuticle protein gene cluster in Drosophila melanogaster.
AB - Proteins of the third instar larval cuticle of Drosophila melanogaster, LCP5
LCP9, were purified and their N-terminal sequences determined. Three of these
proteins (LCP5, 6, and 8) were found to be encoded by two multicopy genes
previously mapped to the gene cluster at 65A 5-6 on the left arm of the third
chromosome. The analysis of the patterns of developmental expression of the 8
distinct genes at this site showed that all but two were expressed during larval
life. The patterns fell into three groups: one where expression was all through
larval life, one where expression was primarily in the third instar, and one only
during the production of the adult cuticle. One duplicated gene was not expressed
in the Canton S strain at any time from the embryo to adult ecdysis. These
findings indicate that there is not a unique set of cuticle proteins in the third
versus the first and second instar larval cuticles and indicates that overlapping
gene sets in several different gene clusters encode the proteins of the cuticle
of different developmental stages.
PMID- 9654738
TI - alpha-Crystallin protein cognates in eggs of the moth, Plodia interpunctella:
possible chaperones for the follicular epithelium yolk protein.
AB - alpha-Crystallin protein cognates were found in germ cells of the Indianmeal
moth, Plodia interpunctella (Shirk and Zimowska, 1997). A cDNA clone of 674 bp
with a single open reading frame was isolated for a 25,000 molecular weight
polypeptide member of this family, alpha CP25, and a single transcript of
approximately 700 bp was found in the ovary of vitellogenic females. Both the DNA
sequence and predicted amino acid sequence showed considerable homology with the
embryonic lethal gene, l(2)efl, in Drosophila melanogaster. In addition to the
sequence for l(2)efl, the predicted amino acid sequence for acp25 also showed
significant sequence similarly with the alpha-crystallin A chain polypeptides
from the lenses of vertebrae eyes. An N-terminal hydrophobic aggregation site and
a C-terminal protective binding site common to alpha-crystallin proteins were
present in the predicted acp25 and l(2)efl amino acid sequences, while only the C
terminal protective binding site was present in the small heat shock protein
sequences from D. melanogaster. This evidence suggests that although the alpha
crystallin protein cognates in P. interpunctella evolved from a gene common with
small heat shock protein genes, the amino acid sequence has converged on a
structure similar to that of alpha-crystallin proteins. Native immunoblot
analysis showed that the alpha-crystallin proteins formed high molecular weight
complexes with the follicular epithelium yolk protein (FEYP) but not vitellin in
yolk. An electroblot binding assay was used to show that the germ-cell alpha
crystallins of P. interpunctella bind specifically with the FEYP and that the
binding was reversible in the presence of ATP or low pH. This evidence in
conjunction with the evidence that the alpha-crystallins and FEYP form a stable
complex that co-purifies from native egg proteins suggests that the alpha
cystallin cognates function as chaperones for the follicular epithelium yolk
proteins in the embryos of P. interpunctella.
PMID- 9654739
TI - Molecular cloning of chitinase cDNAs from the silkworm, Bombyx mori and the fall
webworm, Hyphantria cunea.
AB - cDNAs encoding chitinases were cloned and characterized from Bombyx mori and
Hyphantria cunea, and their gene expression during the metamorphosis was also
studied. The chitinase cDNA from B. mori encodes a protein of 565 amino acids
with a calculated molecular mass of 63.4 kDa and the H. cunea chitinase cDNA
encodes a protein of 553 amino acids with a calculated molecular mass of 62.0
kDa. Amino acid alignment of the two chitinases revealed 75% homology and 77-80%
with M. sexta chitinase. The putative cleavage site of the signal peptide was
between amino acid residues 20 and 21 for both chitinases. There were three
potential N-glycosylation sites in the chitinase of B. mori at the amino acid
residues 86-89, NFTS 304-307, NATG, 398-401, NYTV, whereas two potential N
glycosylation sites were present at the amino acid residues 86-89, NFTA and 304
307, NATG, in that of H. cunea. Southern blot analysis of total genomic DNA
suggested that the B. mori genome has only one chitinase gene detectable by the
cDNA probe and the H. cunea genome has one or two chitinase gene copies. Northern
analysis indicated that gene expression was up-regulated during the molting
process, larval-pupal transformation and pupal-adult transformation, when
enzymatic degradation of cuticle was occurring.
PMID- 9654740
TI - Identification and cDNA cloning of novel juvenile hormone responsive genes from
fat body of the bean bug, Riptortus clavatus by mRNA differential display.
AB - Juvenile hormone (JH) induces termination of diapause and initiation of
reproductive maturation in the adult female bean bug, Riportus clavatus. Applying
PCR-based differential display, we have identified four novel JH-responsive
cDNAS, that is, three repressible (JR-1, 2 and 3) and one inducible (JI-1). These
DNA fragments were partially sequenced and compared with sequences in the data
base. JR-3 was shown to have similarity to the transferrins of other insects,
which have been reported as JH-suppressed genes. JI-1 has similarity to
vitellogenin of Aedes aegypti. On the other hand, JR-1-1 and 2 have no
significant similarity to other known sequences. For JR-1, the full cDNA sequence
was determined: it contained 913 bp, encoding 194 amino acid residues with a
calculated M.W. of 21,531 Da in the mature protein. A total of six JH-responsive
genes or cDNAs (four suppressible and two inducible or stimulated), including the
already isolated JH-responsive cyanoprotein genes (CP-alpha and beta), have been
isolated and are available for further comparative analysis of gene structure and
regulatory mechanisms in the same tissue under the same hormonal conditions.
PMID- 9654741
TI - Characterization and cDNA cloning of a hemoprotein in the salivary glands of the
blood-sucking insect, Rhodnius prolixus.
AB - Three major red hemoproteins, named RpSG I, II (identical with prolixin-S) and
III, in the salivary glands of the blood-sucking insect, Rhonius prolixus, show
homology in N-terminal amino acid (AA) sequences, and are immunologically
related. We focussed on one of these proteins, RpSG-I, in this paper. RpSG-I in
fresh salivary gland extract was separated into two components (Ia and Ib) by
isoelectric focussing gel electrophoresis. Absorption spectra of RpSG-Ia and Ib
showed Soret peaks at 400 nm and 420 nm, respectively, suggesting that they are
nitric oxide (NO)-unbound and -bound hemoproteins and function as NO-carriers.
RpSG-I is stage-specific in appearance, being absent in 3rd and 4th instar
nymphs, appearing and increasing gradually in 5th (last) instar nymphs after
engorgement, and present in the adult stage. We purified RpSG-I from salivary
gland extract by size exclusion and ion exchange HPLCs. It is a single
electrophoretic band with an absorption peak at 400 nm, representing the NO
unbound molecule. Full-size cDNA of RpSG-I was cloned by screening with a
specific polyclonal antibody from a salivary gland cDNA library. Sequence
analysis of RpSG-I cDNA showed an open reading frame encoding a signal peptide
(23 AA) and mature protein (179 AA) of 19,778 daltons. The deduced N-terminal AA
sequence of the RpSG-I was identical with that of the hemoprotein reported as
nitrophorin-3 (Champagne et al., 1995).
PMID- 9654742
TI - Irreversible high pressure inactivation of beta-galactosidase from Kluyveromyces
lactis: comparison with thermal inactivation.
AB - High hydrostatic pressure and high temperature are both shown to induce
inactivation of Kluyveromyces lactis beta-galactosidase in deionised water and
their respective effects are compared. These two physical parameters lead to
similar inactivation kinetics which can be suitably represented by series-type
models. The plot of half-lives as a function of pressure is close to the same
plot towards temperature. Thus, the same inactivation rate constant can be
obtained in two different ways: an increase in pressure at room temperature or an
increase in temperature at atmospheric pressure (e.g. 125 MPa at 25 degrees C or
45 degrees C at 0.1 MPa for a kappa 1 value about 28 x 10(-2) min -1). When beta
galactosidase was prepared in 0.1 M potassium phosphate buffer pH 7.3, its
stability in extreme conditions of pressure as at high temperature was strongly
enhanced. This stabilizing effect of the buffer was essentially attributed to a
pH-effect by comparison with the behaviour of the enzyme in a similar buffer but
with a 10-fold lower ionic strength.
PMID- 9654743
TI - Secretion in Escherichia coli and phage-display of recombinant insulin-like
growth factor binding protein-2.
AB - Insulin-like growth factors (IGFs) promote cell growth and differentiation. Their
actions are regulated by six different, but related, binding proteins (IGFBPs).
To investigate the molecular interactions between IGFs and IGFBPs, an Escherichia
coli based production method and a phage display system has been developed. The
cDNA for bovine IGFBP-2 was inserted between regions coding for the pelB signal
sequence and geneIII product, g3p, of bacteriophage fd in a phagemid vector to
generate pGF14. The coding sequences of IGFBP-2 and g3p were separated by an
amber stop codon and a flexible linker containing the cleavage recognition site
for H64A subtilisin. Using this system in BL21, a non-supE strain lacking ompT,
most product, approximately 4 mg 1(-1) of IGFBP-2, was obtained in the growth
medium. The bacterially derived IGFBP-2 had a correct N-terminal sequence,
molecular mass on SDS-PAGE and the same affinity for IGF-1 and IGF-II as IGFBP-2
from mammalian cells. In a supE strain of E. coli, IGFBP-2 was produced as an IGF
binding fusion to g3p. Procedures for display and approximately 10000 fold
enrichment of IGFBP-2 bearing phage using adsorption to IGF-II coated microtitre
plates were developed. Thus IGFBP-2 can be secreted in E. coli and displayed on
filamentous phage. These can be selectively enriched by binding to immobilised
IGF-II.
PMID- 9654744
TI - Production and characterization of monoclonal anti-idiotypic antibody exhibiting
a catalytic activity similar to carboxypeptidase A.
AB - A new approach for producing catalytic anti-idiotypic antibody was developed. A
monoclonal anti-idiotypic antibody which was induced against carboxypeptidase A
(CPA) showed the catalytic activity similar to the original antigen. The activity
of the catalytic antibody was investigated. Rabbits were immunized by bovine
pancreas carboxypeptidase A. The antiserum was purified and used as antigen to
immunize BALB/c mice to induce monoclonal anti-idiotypic antibodies. Screened for
enzymatic activities, the monoclonal antibody 32C3 showed esterase activity. The
hydrolysis of hippuryl-DL-phenyllactic acid by McAb 32C3 followed the enzymatic
kinetics. In our experimental system, Kcat value was 0.0123 min-1 and Km was
0.04M. The acceleration rate was 1750 times compared to the rate of self
hydrolysis of the substrate. This hydrolysis reaction can be competitively
inhibited by hydrocinnamic acid. This method could be effective to obtain
catalytic antibodies with the characters close to natural enzymes.
PMID- 9654745
TI - In vitro selection of HIV-1 TAR variants by the Tat protein.
AB - Starting from a pool of 10(13) RNA sequences, we isolated a number of TAR RNA
variants after nine rounds of selection by binding to recombinant Tat in vitro
(SELEX procedure). Sequence analysis of part of the selected molecular species
indicated that two TAR variants (clones A and B) were, respectively, represented
five and four times. These two groups of sequences constituted approximately 25%
of the total number of analyzed clones (9/34). As far as the primary and
presumptive secondary structures of the wild-type TAR are concerned, the selected
A and B variants showed an almost complete sequence conservation of the Tat
binding domain, but the configuration of this nucleotide region differed within
the secondary structure. Despite this difference, as verified by gel retardation
and filter binding assays, both the A and B variants bound Tat in vitro with an
affinity that was very close to that of the wild-type TAR. Conversely, neither
variant sustained Tat-mediated trans-activation in vivo when they replaced the
wild-type TAR inside the long terminal repeat of HIV_1. Taken together, our
results suggest that these TAR variants have lost the ability to bind cell
factor(s) in vivo and may therefore represent useful decoys for the inhibition of
HIV-1 replication.
PMID- 9654746
TI - A bienzyme electrode for L-malate based on a novel and general design.
AB - The coimmobilization of a NAD(P) + -dependent dehydrogenase with salicylate
hydroxylase (SHL, EC 1.14.13.1) in front of a Clark-electrode yields a flexible
new design for dehydrogenase based biosensors. The feasibility of the approach
has been tested with malic enzyme (MDH, EC 1.1.1.40) as the dehydrogenase,
resulting in a novel L-malate sensor. It had substantial advantages over the
biosensor approaches reported earlier: effective re-oxidation of NADPH by SHL
yielded an extended linear range from 0.01 to 1.2 mmol 1(-1) L-malate and
strongly reduced NADP+ -requirement (<0.025 mmol 1(-1)), while the working
stability was increased to more than 30 days. The results obtained from six real
samples showed a close correlation with the standard enzymatic method. The
presented scheme with SHL and the Clark-electrode can be employed together with
any NAD(P)+ -dependent dehydrogenase.
PMID- 9654747
TI - Purification and characterization of a highly selective epoxide hydrolase from
Nocardia sp. EH1.
AB - A highly enantioselective, soluble epoxide from Nocardia sp. EH1 was purified to
homogeneity via a four-step procedure: (i) hydrophobic interaction chromatography
on Phenyl Sepharose CL-4B, (ii) anion exchange chromatography on SOURCE 30Q,
followed by (iii) a second hydrophobic interaction chromatography on Phenyl
Sepharose HP, and finally (iv) gel-filtration on Superdex 75 HR 10/30. The pure
protein was shown to be a monomer of integral of 34 kDa possessing an optimum pH
of 8-9. Neither UV-absorbing cofactors nor metal ions were required for activity.
In contrast to whole-cell activity, the partially purified enzyme proved to be
considerably less stable. Stabilization was achieved by addition of non-ionic
detergents such as Tween 80 or Triton X-100, causing a shift of the temperature
optimum from 35 to 40 degrees C. Both effects combined led to an enhancement of
the relative activity of up to approximately 150% of that of the native enzyme.
PMID- 9654748
TI - Recombinant tissue plasminogen activator (rt-PA) in fibrinolytic therapy.
PMID- 9654749
TI - Cinoxacin complexes with divalent metal ions. Spectroscopic characterization.
Crystal structure of a new dinuclear Cd(II) complex having two chelate-bridging
carboxylate groups. Antibacterial studies.
AB - Several cinoxacin (HCx) complexes with divalent metal ions have been prepared and
characterized by spectroscopic techniques. The crystal structure of
[Cd2(Cx)4(H2O)2].10H2O has been determined by X-ray diffraction. The complex is
triclinic, space group P1 with unit-cell dimensions: a = 10.412(2), b =
11.119(2), c = 13.143(6)A, chi== 76.78(4) degrees, beta = 74.59(3) degrees, gamma
= 77.12(3) degrees, V = 1406.0(8) A3. In this complex each cadmium atom is
heptacoordinated: the metal environment is formed by two Oketo and two Ocarbox
atoms from two different cinoxacinate monoanions, two carboxylate oxygen atoms
from a third cinoxacinate ligand and by one water oxygen atom on the seventh
position. Two of the cinoxacinate ions act as tridentate chelate and bridging
ligands and the other one as a bidentate chelate ligand. In the bridging
monoanions the carboxylate group is behaving as a chelate ligand. All the
complexes were screened for their activity against several bacteria, showing
activity similar to that of cinoxacin. Additionally, the number of bacteria
killed after 3 h of incubation with cinoxacin, [Cu(Cx)2].2H2O and
[Co(Cx)3]Na.10H2O complexes was determined against E. coli ATCC 25922; the copper
compound presents paradoxical effect which has been described and related to the
mechanism of action of quinolones.
PMID- 9654750
TI - Interactions of trialkyllead compounds with rat liver mitochondria.
AB - The interactions of two trialkyllead (TAL) compounds, (trimethyl)Pb-Cl and
(tributyl)Pb-Cl, with mitochodria from rat liver have been studied. A stimulation
of the respiratory rate induced by the trialkyllead compounds added at low doses
was observed which was not dependent on the presence of chloride in the medium.
In contrast with the major current view, we propose that trialkyllead compounds
behave as uncouplers of the oxidative phosphorylation and not (or not only) as Cl
/OH- exchangers. In fact the present results suggest that the TAL compounds enter
the mitochondria as (alkyl)3Pb+ cations and are extruded as electroneutral
(alkyl)3 Pb-OH compounds, the overall result being the transport of a proton
through the membrane as in the case of classical uncouplers. The uncoupling
effect could explain the toxicity of the compounds as a result of the decrease in
the energy level of the cell. Furthermore, such a mechanism, in which the uptake
of TAL compounds is supposed to be driven by a negative potential, could explain
their preferential toxicity for neuronal cells, which maintain a higher negative
inside potential than most other cell types.
PMID- 9654751
TI - Binuclear chloro-bridged palladated and platinated complexes derived from p
isopropylbenzaldehyde thiosemicarbazone with cytotoxicity against cisplatin
resistant tumor cell lines.
AB - Two novel dimeric chloro-bridged complexes [Pd (p-is. TSCN) (mu-Cl)]2, 2, and [Pt
(p-is. TSCN)(mu-Cl)]2, 3, where p-is. TSCN = p-isopropylbenzaldehyde
thiosemicarbazone, 1, have been synthesized and characterized by IR and NMR
spectroscopy. The in vitro antitumor activity shown by both compounds against
several human and murine cell lines sensitive and resistant to the clinically
used drug cisplatin (cis-DDP) suggests that compounds 2 and 3 may be endowed with
important anticancer properties. Thus, compounds 2 and 3 not only show IC50
values in the microM range as cis-DDP but also display cytotoxic activity in
tumor cell lines resistant to this drug. The analysis of the interaction of these
binuclear p-is. TSCN compounds with DNA secondary and tertiary structures
indicate that they form DNA interhelical cross-links, a biochemical property that
may be involved in their mechanism of action.
PMID- 9654752
TI - Diorganotin(IV) complexes of pyridoxal thiosemicarbazone: synthesis,
spectroscopic properties and biological activity.
AB - The complexes [SnR2(L)] (R = Me, Et, Bu, Ph; H2L = pyridoxal thiosemicarbazone)
have been prepared and characterized. In the light of the spectral properties of
the complexes in the solid state (IR, mass, Mossbauer) the bideprotonated
thiosemicarbazonato anion is O(phenolic)-, N(3)-, S-bonded to the tin atom which
probably has trigonal bipyramidal coordination with N(3) atom and R groups
occupying equatorial positions. NMR ( 1H, 13C and 119Sn) data in CDCl3 or DMSO-d6
suggest that this coordinative picture remains in these solutions. The ethyl,
butyl and phenyl derivatives suppress proliferation of Friend erithroleukaemia
cells (FLC). Of the pyridoxal thiosemicarbazone complexes so far evaluated.
[SnBu2(L)] and [SnPh2(L)] showed the lowest thresholds for inhibition of FLC
proliferation. The effects of these compounds on DMSO-induced differentiation of
FLC, DNA synthesis and reverse transcriptase were also assayed.
PMID- 9654753
TI - A role for HEM2 in cadmium tolerance.
AB - A Candida glabrata cadmium-sensitive mutant partially defective in glutathione
production and exhibiting a complete absence of phytochelatins was used to clone
a gene required for Cd tolerance. Transformation of the Cd-sensitive mutant with
a genomic library from the wild-type C. glabrata led to the cloning of a gene
that restored Cd tolerance and formation of Cd-glutathione and Cd-phytochelatin
complexes. The cloned gene showed high levels of nucleic acid and protein
sequence homology to the HEM2 genes, encoding porphobilinogen synthases, from
several sources. It was shown that the C, glabrata Cd-sensitive mutant indeed
exhibited a significant reduction in porphobilinogen synthase levels. The cloned
C. glabrata gene complemented a hem2 mutant of Saccharomyces cerevisiae and
restored porphobilinogen synthase activity in the mutant. The Cd sensitive mutant
predictably showed decreased levels of sulfite reductase that requires siroheme,
a metabolite produced in the heme biosynthetic pathway. The addition of cysteine,
but not methionine, increased glutathione levels and Cd tolerance of both the
wild-type and the mutant strain. However, addition of hemin chloride and
methionine together restored Cd tolerance indicating that heme was required for
transsulfuration of homocysteine to cysteine.
PMID- 9654754
TI - The potential of matrix-assisted laser desorption/ionization mass spectrometry in
the quality control of water buffalo mozzarella cheese.
AB - Adulteration by addition of bovine milk to water buffalo milk employed for
mozzarella cheese production is often observed. Water buffalo milk and mozzarella
cheese were analysed by matrix-assisted laser desorption/ionization mass
spectrometry in order to achieve their rapid and accurate characterization and to
evaluate possible fraudulence in mozzarella cheese production.
PMID- 9654755
TI - Hb Sagami [beta 139(H17)Asn-->Thr]: a new hemoglobin variant not detected by
isoelectrofocusing and propan-2-ol test, was detected by electrospray ionization
mass spectrometry.
PMID- 9654756
TI - Measuring individual differences in implicit cognition: the implicit association
test.
AB - An implicit association test (IAT) measures differential association of 2 target
concepts with an attribute. The 2 concepts appear in a 2-choice task (2-choice
task (e.g., flower vs. insect names), and the attribute in a 2nd task (e.g.,
pleasant vs. unpleasant words for an evaluation attribute). When instructions
oblige highly associated categories (e.g., flower + pleasant) to share a response
key, performance is faster than when less associated categories (e.g., insect &
pleasant) share a key. This performance difference implicitly measures
differential association of the 2 concepts with the attribute. In 3 experiments,
the IAT was sensitive to (a) near-universal evaluative differences (e.g., flower
vs. insect), (b) expected individual differences in evaluative associations
(Japanese + pleasant vs. Korean + pleasant for Japanese vs. Korean subjects), and
(c) consciously disavowed evaluative differences (Black + pleasant vs. White +
pleasant for self-described unprejudiced White subjects).
PMID- 9654757
TI - Understanding and assessing the motivations of volunteers: a functional approach.
AB - The authors applied functionalist theory to the question of the motivations
underlying volunteerism, hypothesized 6 functions potentially served by
volunteerism, and designed an instrument to assess these functions (Volunteer
Functions Inventory; VFI). Exploratory and confirmatory factor analyses on
diverse samples yielded factor solutions consistent with functionalist
theorizing; each VFI motivation, loaded on a single factor, possessed substantial
internal consistency and temporal stability and correlated only modestly with
other VFI motivations (Studies 1, 2, and 3). Evidence for predictive validity is
provided by a laboratory study in which VFI motivations predicted the persuasive
appeal of messages better when message and motivation were matched than
mismatched (Study 4), and by field studies in which the extent to which
volunteers' experiences matched their motivations predicted satisfaction (Study
5) and future intentions (Study 6). Theoretical and practical implications are
discussed.
PMID- 9654758
TI - Personality and social change: individual differences, life path, and importance
attributed to the women's movement.
AB - This article identifies antecedent characteristics of individuals who found the
women's movement important and then shows how finding it important was associated
with personality change. Eighty-six women provided personality and life data as
college seniors in 1958 or 1960, prior to the onset of the women's movement, and
in 1981, after the movement gained momentum. A combination of openness, ambition,
and dissatisfaction, as assessed by California Psychological Inventory (CPI; H.
Gough, 1957/1966) in college, and subsequent life path from ages 28 to 43
significantly predicted importance attributed to the women's movement (IWM). On
CPI scales, IWM was associated with significant increases on scales including
Dominance, Self-Acceptance, Empathy, Psychological Mindedness, and Achievement
via Independence. Correlates of IWM with self-reported feelings at ages 33 and 43
and observer-based personality ratings at age 43 supplemented analyses of
personality change. Findings support the utility of examining the impact of
social change on personality.
PMID- 9654759
TI - Heritability of facet-level traits in a cross-cultural twin sample: support for a
hierarchical model of personality.
AB - The common variance among personality traits can be summarized in the factors of
the five-factor model, which are known to be heritable. This study examined
heritability of the residual specific variance in facet-level traits from the
Revised NEO Personality Inventory. Analyses of raw and residual facet scales
across Canadian (183 monozygotic [MZ] and 175 dizogotic [DZ] pairs) and German
(435 MZ and 205 DZ pairs) twin samples showed genetic and environmental
influences of the same type and magnitude across the 2 samples for most facets.
Additive genetic effects accounted for 25% to 65% of the reliable specific
variance. Results provide strong support for hierarchical models of personality
that posit a large number of narrow traits in addition to a few broader trait
factors or domains. Facet-level traits are not simply exemplars of the broad
factors they define; they are discrete constructs with their own heritable and
thus biological basis.
PMID- 9654760
TI - Dysphoria and social interaction: an integration of behavorial confirmation and
interpersonal perspectives.
AB - To investigate the process by which dysphoric persons are rejected by others,
authors integrated behavioral confirmation and interpersonal theories of
depression. The expectations of nondysphoric perceiver participants (college
students) were manipulated, such that half expected to interact with a same-sex
dysphoric target and half expected to interact with a same-sex nondysphoric
target. The targets' actual mood status was consistent or inconsistent with these
expectations. Pre- and postinteraction impressions, as well as postinteraction
acceptance of partners, were solicited from perceivers and targets (N = 240).
Audiotaped verbal behaviors were coded during the 1st and last 3 min of the
interactions. Acceptance of targets and verbal behaviors were an interactive
function of perceivers' expectancies and targets' mood status, such that
dysphoric targets who were expected to be nondysphoric were the least accepted
group and had the most dysfunctional interactions.
PMID- 9654761
TI - A multimodal analysis of personal negativity.
AB - This study examined how unhappiness and self-dissatisfaction are related to
behavior, self-perception, social reputation, and the way one is treated by
others. Varying in personal negativity (PN)--a composite of unhappiness,
dissatisfaction with life, low self-esteem, and nonclinical depression--146
undergraduates (82 women and 64 men) engaged in 3 interactions. Participants'
behavior and the behavior of their interaction partners was coded from
videotapes. Personality ratings were obtained from participants and from 2 close
acquaintances. PN was closely associated with maladaptive social interactions,
negative behavioral responses by others, and a negative social reputation and
self-image. Although women more clearly expressed PN behaviorally, men and women
showed generally similar patterns of correlates. These results suggest that even
subclinical levels of unhappiness and self-dissatisfaction may have important
consequences.
PMID- 9654762
TI - Consequences of self-handicapping: effects on coping, academic performance, and
adjustment.
AB - Self-handicappers erect impediments to performance to protect their self-esteem.
The impediments may interfere with the ability to do well and, as such, may
result in poor adjustment. Using a longitudinal design, the present studies
examined prospective effects of self-handicapping on coping, academic
performance, and several adjustment-related variables (e.g., self-esteem). It was
found that, compared to low self-handicappers, high self-handicappers reported
higher usage of coping strategies implying withdrawal and negative focus. High
self-handicappers performed less well academically, an effect that was mediated
in part by poor study habits. Finally, high self-handicapping resulted in poorer
adjustment over time, and poorer adjustment resulted in higher self-handicapping
over time. These relations are consistent with the idea of a vicious cycle in
which self-handicapping and poor adjustment reinforce one another.
PMID- 9654763
TI - Optimism is associated with mood, coping, and immune change in response to
stress.
AB - This study explored prospectively the effects of dispositional and situational
optimism on mood (N = 90) and immune changes (N = 50) among law students in their
first semester of study. Optimism was associated with better mood, higher numbers
of helper T cells, and higher natural killer cell cytotoxicity. Avoidance coping
partially accounted for the relationship between optimism and mood. Among the
immune parameters, mood partially accounted for the optimism-helper T cell
relationship, and perceived stress partially accounted for the optimism
cytotoxicity relationship. Individual differences in expectancies, appraisal, and
mood may be important in understanding psychological and immune responses to
stress.
PMID- 9654764
TI - Adult attachment styles: their relations to family context and personality.
AB - This study used a sample of 304 adults to examine mean differences in family
climate and personality variables on the basis of individuals' attachment styles.
Also examined was whether mean differences varied by age group. Findings showed
significant main effects of attachment style, but no Attachment Style x Age Group
interactions. Compared with adults with an insecure attachment style, persons
with a secure attachment style described their family of origin and their current
family more positively and scored higher on personality variables indicative of
self-confidence, psychological well-being, and functioning in the social world.
When the family climate and personality variables were included in a discriminant
function analysis, 2 significant functions were obtained. The 1st function
discriminated adults with a positive self-model from those with a negative self
model. The 2nd function contrasted participants with a positive other-model from
those with a negative other-model. Thus, this study provided evidence in support
of the self- and other-models as the fundamental dimensions of adults' attachment
system.
PMID- 9654765
TI - A comparison of coping assessed by ecological momentary assessment and
retrospective recall.
AB - Recent research suggests that retrospective coping assessments may not correspond
well with day-to-day reports. The authors extended this work by examining the
correspondence between short-term (within 48 hr) retrospective coping reports and
momentary reports recorded via a palm-top computer close in time to when the
stressor occurred. There was relatively poor correspondence between the 2
assessments. Some reports of momentary coping were not reported retrospectively,
and some coping reported retrospectively was not reported at the time the
stressor occurred. Cognitive coping was more likely to be underreported
retrospectively; behavior coping was overreported. Participants were consistent
in their discrepancies, but there was no correspondence between discrepancy rates
and demographic or personality variables.
PMID- 9654766
TI - Maladaptive achievement patterns: a test of a diathesis-stress analysis of
helplessness.
AB - The present study tested the assumptions, derived from a diathesis-stress model,
that students' perceptions of autonomy-support in their classroom produce a
relatively intrinsic as opposed to extrinsic motivational approach to academic
tasks and that this approach, in turn, predicts qualitatively different responses
to uncontrollable events. It was further assumed that students' motivational
orientation would be more reliable than attributional style or perceptions of
competence in predicting achievement patterns, including performance level after
failure, use of adaptive attributions, and overall achievement scores. Results
supported these predictions and further demonstrated, in longitudinal analyses,
that motivational orientation may contribute to the formation of perceptions of
competence and attributional style in students.
PMID- 9654767
TI - Dynamics of membrane excitability determine interspike interval variability: a
link between spike generation mechanisms and cortical spike train statistics.
AB - We propose a biophysical mechanism for the high interspike interval variability
observed in cortical spike trains. The key lies in the nonlinear dynamics of
cortical spike generation, which are consistent with type I membranes where
saddle-node dynamics underlie excitability (Rinzel & Ermentrout, 1989). We
present a canonical model for type I membranes, the theta-neuron. The theta
neuron is a phase model whose dynamics reflect salient features of type I
membranes. This model generates spike trains with coefficient of variation (CV)
above 0.6 when brought to firing by noisy inputs. This happens because the timing
of spikes for a type I excitable cell is exquisitely sensitive to the amplitude
of the suprathreshold stimulus pulses. A noisy input current, giving random
amplitude "kicks" to the cell, evokes highly irregular firing across a wide range
of firing rates; an intrinsically oscillating cell gives regular spike trains. We
corroborate the results with simulations of the Morris-Lecar (M-L) neural model
with random synaptic inputs: type I M-L yields high CVs. When this model is
modified to have type II dynamics (periodicity arises via a Hopf bifurcation),
however, it gives regular spike trains (CV below 0.3). Our results suggest that
the high CV values such as those observed in cortical spike trains are an
intrinsic characteristic of type I membranes driven to firing by "random" inputs.
In contrast, neural oscillators or neurons exhibiting type II excitability should
produce regular spike trains.
PMID- 9654768
TI - Category learning through multimodality sensing.
AB - Humans and other animals learn to form complex categories without receiving a
target output, or teaching signal, with each input pattern. In contrast, most
computer algorithms that emulate such performance assume the brain is provided
with the correct output at the neuronal level or require grossly unphysiological
methods of information propagation. Natural environments do not contain explicit
labeling signals, but they do contain important information in the form of
temporal correlations between sensations to different sensory modalities, and
humans are affected by this correlational structure (Howells, 1944; McGurk &
MacDonald, 1976; MacDonald & McGurk, 1978; Zellner & Kautz, 1990; Durgin &
Proffitt, 1996). In this article we describe a simple, unsupervised neural
network algorithm that also uses this natural structure. Using only the co
occurring patterns of lip motion and sound signals from a human speaker, the
network learns separate visual and auditory speech classifiers that perform
comparably to supervised networks.
PMID- 9654769
TI - A hierarchical model of binocular rivalry.
AB - Binocular rivalry is the alternating percept that can result when the two eyes
see different scenes. Recent psychophysical evidence supports the notion that
some aspects of binocular rivalry bear functional similarities to other bistable
percepts. We build a model based on the hypothesis (Logothetis & Schall, 1989;
Leopold & Logothetis, 1996; Logothetis, Leopold & Sheinberg, 1996) that
alternation can be generated by competition between top-down cortical
explanations for the inputs, rather than by direct competition between the
inputs. Recent neurophysiological evidence shows that some binocular neurons are
modulated with the changing percept; others are not, even if they are selective
between the stimuli presented to the eyes. We extend our model to a hierarchy to
address these effects.
PMID- 9654770
TI - Pattern generation by two coupled time-discrete neural networks with synaptic
depression.
AB - Numerous animal behaviors, such as locomotion in vertebrates, are produced by
rhythmic contractions that alternate between two muscle groups. The neuronal
networks generating such alternate rhythmic activity are generally thought to
rely on pacemaker cells or well-designed circuits consisting of inhibitory and
excitatory neurons. However, experiments in organotypic cultures of embryonic rat
spinal cord have shown that neuronal networks with purely excitatory and random
connections may oscillate due to their synaptic depression, even without
pacemaker cells. In this theoretical study, we investigate what happens if two
such networks are symmetrically coupled by a small number of excitatory
connections. We discuss a time-discrete mean-field model describing the average
activity and the average synaptic depression of the two networks. Depending on
the parameter values of the depression, the oscillations will be in phase,
antiphase, quasiperiodic, or phase trapped. We put forward the hypothesis that
pattern generators may rely on activity-dependent tuning of synaptic depression.
PMID- 9654771
TI - Computational studies of lateralization of phoneme sequence generation.
AB - The mechanisms underlying cerebral lateralization of language are poorly
understood. Asymmetries in the size of hemispheric regions and other factors have
been suggested as possible underlying causal factors, and the corpus callosum
(interhemispheric connections) has also been postulated to play a role. To
examine these issues, we created a neural model consisting of paired cerebral
hemispheric regions interacting via the corpus callosum. The model was trained to
generate the correct sequence of phonemes for 50 monosyllabic words (simulated
reading aloud) under a variety of assumptions about hemispheric asymmetries and
callosal effects. After training, the ability of the full model and each
hemisphere acting alone to perform this task was measured. Lateralization
occurred readily toward the side having larger size, higher excitability, or
higher-learning-rate parameter. Lateralization appeared most readily and
intensely with strongly inhibitory callosal connections, supporting past
arguments that the effective functionality of the corpus callosum is inhibitory.
Many of the results are interpretable as the outcome of a "race to learn" between
the model's two hemispheric regions, leading to the concept that asymmetric
hemispheric plasticity is a critical common causative factor in lateralization.
To our knowledge, this is the first computational model to demonstrate
spontaneous lateralization of function, and it suggests that such models can be
useful for understanding the mechanisms of cerebral lateralization.
PMID- 9654772
TI - Debunking the alleged resurrection of the sodium pump hypothesis.
PMID- 9654773
TI - Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl
phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide
generation in human neutrophils.
AB - Human peripheral blood polymorphonuclear leukocytes were preincubated with
lanthionine, S-(2-aminoethyl)-L-cysteine, and some of their derivatives found in
normal human urine and bovine brain. Among these compounds, lanthionine ketimine
and to a lesser extent S-(2-aminoethyl)- L-cysteine ketimine enhanced the N
formyl-methionyl-leucyl-phenylalanine-induced superoxide generation. These
ketimines induced tyrosyl phosphorylation of 45 kDa protein of cells. The tyrosyl
phosphorylation was markedly increased with time, and the phosphorylation process
was dependent on the concentration of both ketimines. However, lanthionine, 1,4
thiomorpholine-3,5-dicarboxylic acid, S-(2-aminoethyl)-L-cysteine and 1,4
thiomorpholine-3-carboxylic acid were without effect both on superoxide
generation and on tyrosyl phosphorylation of 45 kDa protein. Lanthionine ketimine
and S-(2-aminoethyl)-L-cysteine ketimine also enhanced superoxide generation
induced by opsonized zymosan but not the one induced by arachidonic acid and
phorbol 12-myristate 13-acetate. Ketimine-primed superoxide generation and
tyrosyl phoshorylation of 45 kDa protein were inhibited by genistein, an
inhibitor of protein tyrosine kinase, but not by 1-(5-isoquinoline sulfonyl)-2-
methylpiperazine, an inhibitor of protein kinase C.
PMID- 9654774
TI - Electrolyte concentration in skeletal muscles and plasma of rats during and after
exposure to hypokinesia and hyperhydration.
AB - The objective of this investigation was to determine electrolyte concentration in
skeletal muscles and plasma of rats during 90 days of hypokinesia (decreased
motor activity) and 15 days of posthypokinesia. The animals were divided into
three groups: 1) supplemented hypokinetic rats (SHR), i.e., rats subjected to
hypokinesia and taking daily an additional 9 ml water per 100 g body weight plus
6 ml isotonic sodium chloride per 100 g body weight; 2) unsupplemented
hypokinetic rats (UHR), i.e., rats subjected to hypokinesia; 3) vivarium control
rats (VCR), i.e., rats placed under ordinary vivarium conditions. Hypokinesia was
effected by keeping SHR and UHR animals in small individual cages that restricted
their movements in all directions without hindering food and water intake.
Determinations were made of water and electrolyte (sodium potassium, calcium,
magnesium) concentrations in muscle tissue; concentration of electrolytes
(sodium, potassium, calcium, magnesium, phosphorus, chloride) in plasma; body
weight; fluid consumed and eliminated in urine; whole blood, red blood cell and
plasma volumes; hematocrit content and plasma protein concentration. During the
hypokinetic period, electrolytes and water concentration in muscle tissue and
plasma electrolyte concentration changes significantly in the UHR when compared
with SHR and VCR while in comparing the SHR with the VCR these same variables had
no significant changes. Body weight, water balance, volume of blood, red blood
cell and plasma, hematocrit and plasma protein concentration in the UHR were also
significantly different when compared with the VCR. No significant difference was
seen in these parameters when the SHR and VCR were compared. During the initial
seven days of the posthypokinetic period the changes in these same parameters
remained significantly different in the UHR when compared with the SHR and VCR
while changes were insignificant when the SHR and the VCR were compared. It was
concluded that daily hyperhydration may be used to attenuate or normalize water
and electrolyte concentrations in muscles and plasma of rats subjected to
prolonged restriction of motor activity.
PMID- 9654775
TI - Biotransformation of shiromodiol diacetate, myli-4(15)-en-9-one and myliol by
Aspergillus niger.
AB - Microbiol biotransformation of shiromodiol diacetate from Neolitsea serisea
koids, and of myli-4(15)-en-9-one and myliol from the liverwort Mylia taylorii,
were carried out with Aspergillus niger IFO 4407. A. niger hydroxylated the allyl
position (C-2) of shiromodiol diacetate, and one of the geminal dimethyl groups
of myli-4(15)-en-9-one and myliol regioselectively. The structures of these
transformants were elucidated by spectral analysis and confirmed by X-ray
analysis.
PMID- 9654776
TI - Steroidal saponins from the underground parts of Ruscus aculeatus and their
cytostatic activity on HL-60 cells.
AB - Phytochemical examination of the underground parts of Ruscus aculeatus has been
undertaken as part of systematic study of plants of the Liliaceae. Six new
spirostanol saponins and five new furostanol saponins were isolated, and their
structures were assigned on the basis of spectroscopic analysis, including two
dimensional NMR techniques, and hydrolysis. Ruscogenin diglycoside with three
acetyl groups attached to the inner galactosyl moiety and its corresponding 26
glucosyloxyfurostanol saponin showed cytostatic activity on leukemia HL-60 cells.
PMID- 9654777
TI - Alphitol, a phenolic substance from Alphitonia zizyphoides which inhibits
prostaglandin biosynthesis in vitro.
AB - The new phenolic compound, 3,5-dihydroxy-4-methoxy phenethyl alcohol, named
alphitol, and betulinic acid were from the bark of Alphitonia zizyphoides. The
chemical structure of alphitol was determined by mass spectrometry in combination
with one and two dimensional NMR, including HMBC. Both compounds inhibited
prostaglandin biosynthesis in vitro, alphitol with an IC50 value of 0.66mM, which
is of the same magnitude as acetyl salicylic acid.
PMID- 9654778
TI - A hydroxytetradecatrienoic acid from Mycosphaerella rubella.
AB - Investigations on the acidic fractions from extracts of a culture of
Mycosphaerella rubella led to the isolation of a new unsaturated dihydroxy acid,
6,13-dihydroxytetradeca-2,4,8 trienoic acid, and two of its derivatives, which
are probably artifacts. Their structures were determined on the basis of H and C
NMR evidence. The absolute configuration of the chiral centres of the new acid
was elucidated using the modified Mosher's method.
PMID- 9654779
TI - Triterpenoid saponins and sapogenins from Vaccaria segetalis.
AB - Four new triterpenoid saponins, vaccarosides E, F, G and H were isolated from the
seeds of Vaccaria segatalis and were respectively defined to be 3-O-beta-D
galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl] quillaic acid 28-O-beta-D
xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl-(1-
>3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D
glucuronopyranosyl] 3beta,4chi,16chi-trihydroxy-23-norolean-12-en-28-oic acid 28
O-beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L
arabinofuranosyl-(1-->3)]-beta-D-4-O-acetylfucopyranoside; 3-O-[beta-D
galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] gypsogenin 28-O-beta-D
xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2)- [chi-L-arabinofuranosyl (1-
>3)]-beta-D-4-O-acetylfucopyranoside; and 3-O-[beta-D-galactopyranosyl-(1-->2)
beta-D-glucuronopyranosyl] 3beta,4chi-dihydroxy-23norolean-12-en-28-oic acid 28-O
beta-D-xylopyranosyl-(1-->4)-chi-L-rhamnopyranosyl-(1-->2) -chi-L
arabinofuranosyl-(1-->3)]-beta-D-4-O-acetyfucopyranoside. Their structures were
established on the basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC AND
NOESY), FAB-MS and ESI-MS studies as well as chemical strategies and enzymatic
degradation. The new aglycones of two of the saponins have been designated as
segetalic acid and vaccaric acid, respectively.
PMID- 9654780
TI - Three phenylethanoid glycosides and an iridoid glycoside from Picrorhiza
scrophulariiflora.
AB - Three new phenylethanoid glycoside, named scrosides A-C and a new iridoid
glycosides, named picroside IV, have been isolated from the underground parts of
Picrorhiza scrophulariiflora, together with 11 known compounds. Their structures
were elucidated by the means of 2D NMR spectroscopy and chemical methods.
PMID- 9654781
TI - Emergence of collective strategies in a prey-predator game model.
AB - The emergence of collective strategies in a prey-predator system is studied. We
use the term "collective" in the sense of the collective motion of defense or
attack often found in behaviors of animal groups. In our prey-predator system,
both prey and predators move around on a two-dimensional plane, interacting by
playing a game; predators can score by touching the backside of a prey.
Thresholds are assumed for the scores of both prey and predators. The species
with the higher scores can reproduce more, and that with the lower scores will be
diminished. As a result, strategies as collective motions are observed; these
consist of rotating cluster motions, line formations, disordered but one-way
marching, and random swarming. In particular, the strategy of random swarming
encourages symbiosis in the sense that it is associated with a low extinction
probability for the whole system.
PMID- 9654782
TI - An ecology of text: using text retrieval to study alife on the net.
AB - I introduce a new alife model, an ecology based on a corpus of text, and apply it
to the analysis of posts to USENET News. In this corporal ecology posts are
organisms, the newsgroups of NetNews define an environment, and human posters
situated in their wider context make up a scarce resource. I apply latent
semantic indexing (LSI), a text retrieval method based on principal component
analysis, to distill from the corpus those replicating units of text. LSI arrives
at suitable replicators because it discovers word co-occurrences that segregate
and recombine with appreciable frequency. I argue that natural selection is
necessarily in operation because sufficient conditions for its occurrence are
met: replication, mutagenicity, and trait/fitness covariance. I describe a set of
experiments performed on a static corpus of over 10,000 posts. In these
experiments I study average population fitness, a fundamental element of
population ecology. My study of fitness arrives at the unhappy discovery that a
flame-war, centered around an overly prolific poster, is the king of the jungle.
PMID- 9654783
TI - A robot trace maker: modeling the fossil evidence of early invertebrate behavior.
AB - The study of trace fossils, the fossilized remains of animal behavior, reveals
interesting parallels with recent research in behavior-based robotics. This
article reports robot simulations of the meandering foraging trails left by early
invertebrates that demonstrate that such trails can be generated by mechanisms
similar to those used for robot wall-following. We conclude with the suggestion
that the capacity for intelligent behavior shown by many behavior-based robots is
similar to that of animals of the late Precambrian and early Cambrian periods
approximately 530 to 565 million years ago.
PMID- 9654784
TI - EUZONE: simulating the evolution of aquatic ecosystems.
AB - In the spirit of contemporary artificial life research, EUZONE provides a virtual
laboratory for the emergence of complex ecosystems from simple primitives.
However, whereas most alife systems abstract away many real-world environmental
constraints, EUZONE employs detailed physical and chemical models in combination
with evolutionary algorithms to support the emergence of carbon-based aquatic
ecosystems. With an emphasis on plankton-like organisms, this research focuses
upon the self-organization and evolution of (a) lower levels of aquatic food
webs, (b) Gaian interactions between primitive organisms and their physical
environments, and (c) species interactions governed by varying life-history
strategies.
PMID- 9654785
TI - 1997 declaration of the environment leaders of the Eight on children's
environmental health.
AB - On May 5-6, 1997, Administrator Carol M. Browner hosted the Environment Leaders'
Summit of the G7 countries plus Russia, known as "the Eight," in Miami, Florida.
Children's Environmental Health was the centerpiece topic for discussion at the
Summit, which resulted in the 1997 Declaration of the Environment Leaders of the
Eight on Children's Environmental Health and its annexed Implementation Actions
on Protecting Children's Health and Environment Which the Environment Leaders of
the Eight Have Agreed to Promote Within Their Governments and Countries. These
documents provide a framework for domestic, bilateral and international efforts
to improve the protection of children's health from environmental threats and
specify concrete actions that the Eight will undertake to begin the process of
incorporating characteristics of infants and children into environmental science,
risk assessments and protection regimes.
PMID- 9654786
TI - Children are different: environmental contaminants and children's health.
AB - Although the impact of environmental contaminants on human health has been widely
studied, few reports in the Canadian literature have focussed on the specific
vulnerability of children. Because of their rapid growth, physiologic and
metabolic immaturity, the fetus and child are often at increased risk from toxic
substances in their environments. Furthermore, greater air, food and fluid
intakes relative to body weight compared with the adult, increase the child's
potential for excessive exposures. The crawling stage of infancy, the play
patterns and short stature of toddlers also serve to increase their exposure to
dust and heavy and volatile substances which accumulate near the floor. This
article provides an overview of some of the developmental physiologic, anatomic
and behavioural features of the fetus, infant and child which increase their
vulnerability to environmental contaminants in comparison with adults. Specific
examples are given.
PMID- 9654787
TI - The case for child development as a determinant of health.
AB - The complex relationship between life course and social/economic-psychosocial
conditions in a given society has a powerful determining effect on human health.
The socioeconomic gradient emerges from a complex mixture of psychosocial and
material influences operating at various levels of social aggregation and, also,
a series of biological responses whose character and significance vary over the
life course. Biological embedding and the "latency" and "pathways" model
incorporate the notion of a critical period in development; the pathways model
emphasizes the cumulative effect of life events and the ongoing importance of
social/economic-psychosocial conditions throughout the life cycle. The models,
although conceptually complementary, result in ideological conflict and lend
themselves to different policy directions.
PMID- 9654788
TI - Prenatal exposure of Canadian children to polychlorinated biphenyls and mercury.
AB - This article documents the exposure to environmental contaminants within sub
groups of the Canadian population who are considered to be at risk as a result of
the food they eat. We measured the concentrations of polychlorinated biphenyls
(PCBs) and mercury in the blood drawn from the umbilical cords of newborns in
various Aboriginal communities, in a coastal community and in the general
population. Average concentrations of Aroclor 1260 ranged between 0.3 and 2.0
micrograms/L and were clearly highest among the Inuit of Nunavik and Baffin
Island and among the Montagnais of Quebec. In these groups, we found contaminant
levels in the blood of newborns that exceed the threshold beyond which cognitive
impairments are expected to result. Average concentrations of mercury ranged
between 1.0 and 14.2 micrograms/L; the Inuit of Nunavik and the NWT exhibited the
highest exposure levels. A portion of the Nunavik and NWT Inuit had
concentrations beyond the critical threshold for the appearance of neurological
consequences. The variations in exposure levels resulted from the different
nutritional practices of these Canadian sub-groups.
PMID- 9654789
TI - Child health, poverty and the environment: the Canadian context.
AB - In Canada, there has been little research exploring the link between child
poverty and exposure to environmental contaminants. However, children living in
poverty are more likely to grow up in neighbourhoods adjacent to polluting
industries and heavily used transportation corridors. They are also more likely
to live in improperly designed or maintained buildings where levels of
contaminants and toxic residuals may be high, and indoor air quality poor. Risk
factors such as exposure to cigarette smoke and poor nutritional status, together
with the above living conditions during growth and development, create conditions
that make children living in poverty more vulnerable to the effects of
environmental contaminants. In Toronto, the South Riverdale Community Health
Centre is developing grassroots techniques to build awareness and protect
citizens. Given the growing levels of child poverty in Canada and decreasing
environmental protection, the author suggests increased community action and
health research for use in advocating for appropriate policy changes.
PMID- 9654790
TI - Issues in developmental neurotoxicology: interpretation and implications of the
data.
AB - The potential for environmental contaminants to produce neurological, cognitive,
or other behaviour deficits as a result of developmental exposure has received
increasing attention. The focus has shifted from description of frank
neurotoxicity observed in a relatively few individuals to more subtle impairment
in a much greater number of children. With this shift has come the recognition
that subtle deficits such as a small decrease in IQ can have important societal
impact when large numbers of children are affected. For example, the result of a
1 microgram/dL decrease in blood lead concentration in children in the United
States with blood lead concentrations between 10 and 20 micrograms/dL would
translate into a savings of 5-7.5 billion U.S. dollars a year in increased
earning power alone. In addition, behavioural problems such as increased
aggression and poor social adjustment identified early in childhood may escalate
to serious antisocial behaviour such as delinquency as the child approaches
puberty. Exposure to neurotoxic agents during development or over a significant
portion of the lifespan may also result in acceleration of age-related
neurodegenerative diseases. Such changes in the functional abilities of a
significant proportion of a population have potentially serious consequences for
society as well as for affected individuals.
PMID- 9654791
TI - Endocrine disruptors and development of the reproductive system in the fetus and
children: is there cause for concern?
AB - Reports of decreased semen quality and increased rates of developmental
abnormalities of the male reproductive tract along with increasing incidence of
testicular cancer have focused attention on man-made chemicals as potential
causative factors. A biologically plausible hypothesis has been advanced which
suggests that man-made chemicals act as endocrine disruptors through interaction
with the estrogen receptor resulting in altered development of the reproductive
tract. Available evidence suggests that this mechanism may play only a minor role
in the purported adverse effects described to date. Man-made chemicals, however,
may induce adverse health effects through mechanisms independent of the estrogen
receptor. Indeed, man-made chemicals have been shown to induce adverse effects on
thyroid function and androgen-dependent processes in animal studies. Hence the
focus on estrogenic mimics may be too simplistic and alternate mechanisms could
be more relevant due to target gland exposure levels and potency of the toxicant.
Before it can be concluded that man-made chemicals pose little or no risk to the
development of the reproductive tract in the fetus and children it will be
necessary to, at the very least, insure that: 1) exposure scenarios include the
most sensitive developmental stage, 2) all endocrine targets have been evaluated
for potential effects, and 3) the role of environmentally and biologically
relevant levels of chemical mixtures in adverse health outcomes have been
evaluated. Due to potential for exposure, sensitivity of the developing
reproductive tract, suggestive evidence of a possible role of man-made chemicals
in developmental abnormalities of the reproductive tract, and the many
outstanding research questions, it is concluded that there is sufficient cause
for concern.
PMID- 9654792
TI - Air pollution exposures and children's health.
AB - The evidence from a large number of studies indicates that exposures to current
outdoor air pollution increase respiratory morbidity in children. Children with
asthma, and those with asthma-like symptoms but without a diagnosis of asthma,
are considered to be at highest risk of experiencing short-term and/or longer
term adverse health effects. Many outdoor air pollutants readily penetrate
indoors. Indoor air quality can deteriorate quickly when persistent and
uncontrolled emissions occur and the ventilation/air exchange rate is reduced. It
has been estimated that children spend 90% of their time indoors, including in
school buildings, vehicles and public indoor environments. Environmental tobacco
smoke is a well-recognized persistent indoor air contaminant with adverse health
effects in children of all ages. Uncontrolled moisture in the indoor environment
is increasingly recognized to significantly increase the risk of respiratory
morbidity in children. The evidence that air pollutants singly and in combination
with other environmental factors elicit adverse health responses in asthmatic and
non-asthmatic children and adolescents, appears irrefutable.
PMID- 9654793
TI - The impact of PCBs and dioxins on children's health: immunological
considerations.
AB - Environmental contaminants include the potentially toxic metals lead, cadmium and
mercury; the chlorinated pesticides mirex, toxaphene and hexachlorobenzene;
chlorinated dioxins and furans; polyaromatic hydrocarbons; and polychlorinated
biphenyls. While many of these chemicals are resistant to degradation in the
natural environment, they dissolve readily in oils and thus accumulate in the
fatty tissues of fish, birds and mammals. Human exposure is predominantly through
the ingestion of contaminated food. An array of toxic effects including effects
on the immune system have been described in experimental animals and in humans
accidentally exposed to these chemicals. Such studies suggest that the immune
system of the developing fetus and the newborn is particularly vulnerable to the
toxic effects of chemicals. To fully appreciate the magnitude of risk these
chemicals pose to children's health, there is a need for additional carefully
focussed epidemiologic and mechanistic studies.
PMID- 9654794
TI - Childhood cancer and environmental contaminants.
AB - This article reviews the available epidemiologic evidence for relationships
between the development of cancer in childhood and environmental agents,
specifically chemicals, ionizing radiation, low-frequency electromagnetic fields,
and infectious agents. Chemical exposures include medications and other drugs,
components of diet, and second-hand exposure to industrial chemicals and to
environmental carcinogens. Ionizing radiation is the only well-established risk
factor for childhood cancers. Suggestive associations with excess childhood
cancer risk have been found with exposures to paints, petroleum products,
solvents, pesticides and metals. An excess risk of brain tumours has been
reported with ingestion of n-nitroso compounds, and there have been positive
findings relating leukemia risk and infections. Studies of risk of childhood
cancer with parental use of alcohol and with parental smoking have been generally
negative, while the inconsistencies and generally low risks reported in studies
of power-frequency electromagnetic fields do not support a causal relationship.
PMID- 9654795
TI - Role of health professionals in protecting children from environmental risks: a
commentary.
AB - Health professionals are well positioned to protect children from environmental
exposures to toxicants. Doing so may mean mobilizing for precautionary action
well before conclusive evidence of adverse health impacts are documented in the
community. This paper comments on the context within which health professionals
work, and identifies strengths, barriers and guiding principles for action. Roles
and strategies are identified for both medically and community-focussed health
professionals. The prevention--treatment continuum (global action--policy and
regulatory reform--local collective action--health protection--medical treatment)
is explored. While health professionals traditionally deal with the treatment
(downstream) end of the spectrum in addressing environmental health problems,
there are ample opportunities for expanding this role to the prevention
(upstream) end. Applicable strategies are organized into six major roles:
surveillance, hazard assessment, research, education, public awareness, and
advocacy. Advocacy is one of the most important roles since it involves upstream
activities close to the source of the problem. While downstream endeavours have a
legitimate place in the practice of health professionals, expanding this role to
include upstream strategies, such as health promotion and advocacy, is essential
if efforts to protect children's health are to succeed in the long term.
PMID- 9654796
TI - Air pollution: the environmental phoenix.
PMID- 9654797
TI - The effect of the urban ambient air pollution mix on daily mortality rates in 11
Canadian cities.
AB - OBJECTIVE: Determine the risk of premature mortality due to the urban ambient air
pollution mix in Canada. METHODS: The number of daily deaths for non-accidental
causes were obtained in 11 cities from 1980 to 1991 and linked to concentrations
of ambient gaseous air pollutants using relative risk regression models for
longitudinal count data. RESULTS: Nitrogen dioxide had the largest effect on
mortality with a 4.1% increased risk (p < 0.01), followed by ozone at 1.8% (p <
0.01), sulphur dioxide at 1.4% (p < 0.01), and carbon monoxide at 0.9% (p = 0.04)
in multiple pollutant regression models. A 0.4% reduction in premature mortality
was attributed to achieving a sulphur content of gasoline of 30 ppm in five
Canadian cities, a risk reduction 12 times greater than previously reported.
CONCLUSIONS: Ambient air pollution generated from the burning of fossil fuels is
a risk factor for premature mortality in 11 Canadian cities.
PMID- 9654798
TI - Car phones and car crashes: an ecologic analysis.
AB - OBJECTIVE: Some countries have regulations against using a cellular telephone
while driving. We used ecologic analysis to evaluate cellular telephone use and
motor vehicle collisions in a city without such regulations. METHODS: We studied
locations in Toronto, Ontario (n = 75) that were hazardous (total collisions =
3,234) and tested whether increases in collision rates from 1984 to 1993
correlated with increases in telephone usage over the same time interval.
RESULTS: Locations with the largest increases in collision rates tended to have
the smallest increases in estimated cellular telephone usage. Yet extreme
assumptions about potential protective effects from cellular telephones failed to
explain the magnitude observed. CONCLUSIONS: The effects of cellular telephones
on driving ability are small relative to the biases in ecologic analysis. Claims
from industry, which argue that cellular telephones are not dangerous based on
ecologic analysis, can be misleading in the policy debate about whether to
regulate cellular telephone use while driving.
PMID- 9654799
TI - Knowledge, perception and behaviour of the general public concerning the addition
of fluoride in drinking water.
AB - A telephone survey was carried out in 1994, in the Quebec City region, among 1006
people living in two municipalities where tap water is fluoridated and 1003
people living in two municipalities where there is no fluoridation. Knowledge of
the main benefit associated with the use of fluoride (prevention of tooth decay)
in drinking water was not different in fluorated versus non-fluoridated
municipalities (20.4% vs 19.4%, p = 0.57). Knowledge of its main disadvantage
(increase of dental fluorosis) was very low and similar in both groups (3.1% vs
2.0%, p = 0.11). Opposition to fluoridation was slightly higher in fluoridated
areas (22.0% vs 18.3%, p = 0.04), and the use of fluoridated supplements for
children was much less important in fluoridated areas (4.4% vs 12.4%, p = 0.001).
No changes in the measures of association (odds ratios) were found after
adjustment for the different characteristics of the participants (age, family
income, education). Opposition to fluoridation was lower among those who believed
their tap water was fluoridated (even if not): 19.9% vs 34.5%, p < 0.001. This
study demonstrates that there is still need for public health education on the
uses of fluorides.
PMID- 9654800
TI - One year outcome evaluation of an alcohol and drug abuse prevention program in a
Quebec high school.
AB - This article presents the results of a one-year outcome evaluation of a school
based alcohol- and drug-abuse prevention program targeting adolescents in Quebec.
This evaluation concerns the school component of the program and includes the
first seven classroom interventions. The design is a pre- and post-intervention
assessment of both the experimental (n = 145 students) and the control school (n
= 179 students). Results obtained do not reveal any significant effect of the
program on knowledge and beliefs regarding the use of alcohol and drugs, or any
modification in self-efficacy with respect to decision making and ability to
resist external pressure concerning the decision to use marijuana/hashish. The
results do show, however, a decrease among the exposed students in self-efficacy
within the context of alcohol use. Such a result may be a consequence of the
program's capacity to raise the students' level of awareness of their
susceptibility to social influences. It is plausible that in order to have
positive effects, classroom interventions such as the present one need to be
supplemented by additional activities targeting youths' environment.
PMID- 9654801
TI - A cardiovascular health needs assessment of university students living in
residence.
AB - The purpose of this study was to determine the cardiovascular health needs of
university students living in residence. A survey was administered to students
living in residence at a university in Nova Scotia, Canada to identify eating
patterns, physical activity, smoking behaviours and perceived stress. Data were
analyzed using descriptive statistics and chi-square tests of association.
Qualitative data were collected using focus group interviews. Results showed that
fewer than half of the students participated in exercise three or more times per
week, and 82% are less than the recommended amount of fruits and vegetables. As
perceived knowledge of CVD increased so did level of physical activity and
consumption of fruits and vegetables. Fifty-six percent of students rated their
stress as high or very high; exams and course assignments are a major cause of
this stress. Fifteen percent of the university students surveyed were daily
smokers. Barriers to a healthy lifestyle include time constraints and limited
food choices in the residence cafeteria.
PMID- 9654802
TI - [Effectiveness of an educational intervention in improving the self concept of
second to sixth grade students].
AB - This study evaluated the effectiveness of an intervention in improving the
general, academic, physical and social self-concepts of 2nd to 6th grade
students. The activities were carried out by the teachers during the 1992-93
school year. A questionnaire was completed by 271 students of the experimental
school and by 467 students of the control school, both before and after the
intervention. The multiple regression analyses showed important adjusted gains
for self-concepts related to physical appearance, mathematics and relationship
with parents. In all three cases, students with the largest deficit benefitted
most from the intervention. This study shows that it is possible to improve self
concept and to do so through an intervention carried out in the school
environment. This double finding is important to the promotion of psycho-social
adaptation since self-concept is an important determinant and since few
interventions have reached similar objectives.
PMID- 9654803
TI - Gender differences in the prevalence of depression among Canadian adolescents.
PMID- 9654804
TI - [Evaluation and validation of a test of psychological distress in a general
population in french Quebec].
AB - Psychological distress scales used in epidemiologic surveys usually show high
construct validity. The content validation however is less convincing since these
scales rest on lists of psychiatric symptoms which are hypothesized as the very
content of a psychological distress. This study presents the results of the
construct and criterion validation of a new Psychological Distress Manifestations
Measure Scale (PDMMS) founded on an initial list of manifestations derived from
an original content validation in a general population. Twenty-three items are
grouped in four oblique factors with Cronbach's alpha ranging between 0.81 and
0.89. High scores on the scale are correlated with psychoactive drugs
consumption, visits to health professionals and self-evaluations of psychological
health.
PMID- 9654805
TI - Alberta's infant mortality rate: the effect of the registration of live newborns
weighing less than 500 grams.
PMID- 9654806
TI - Diet survey of two cultural groups in a coastal British Columbia community.
AB - OBJECTIVES: As part of a larger study of polychlorinated dibenzodioxin (PCDD) and
dibenzofuran (PCDF) pollution, to describe and compare Aboriginal and non
Aboriginal residents' recalled diets. METHODS: We surveyed a stratified random
sample aged 25 to 64 years: forest products mill employees (n = 84), Aboriginal
reserve residents (n = 78), and other residents (n = 80). We administered a
questionnaire on intake of fish/seafood, wild game and plants, domesticated
animal meat and eggs, dairy products, vegetable oils and cereals; age, gender,
childbearing, lactation, residence and smoking. We measured height and weight.
RESULTS: Reserve residents ate less seafood, but more fish roe, eulachon grease,
smoked salmon, clams and sea urchins, more deer organs, hamburger meat, pork,
fried chicken, and hot-dogs, but less rabbit, beef steaks/roasts, high-fibre
cereals, potato chips, bread, cheese and milk. CONCLUSIONS: We cannot yet
quantify PCDD and PCDF intakes. The wild food consumption data are unique and may
be useful for risk assessments in the target population and similar communities.
PMID- 9654807
TI - Effectiveness of public health interventions in food safety: a systematic review.
AB - PURPOSE: To summarize evidence on the effectiveness of public health
interventions regarding food safety at restaurants, institutions, homes and other
community-based settings. METHOD: This systematic review of published and
unpublished studies involved a comprehensive literature search, screening for
relevance, quality assessment of relevant studies, data extraction and synthesis.
RESULTS: The interventions identified in 15 studies included in this review were
grouped into three categories: inspections, food handler training, and community
based education. The evidence suggests that: routine inspection (at least once
per year) of food service premises is effective in reducing the risk of foodborne
illness; food handler training can improve the knowledge and practices of food
handlers; and selected community-based education programs can increase public
knowledge of food safety. DISCUSSION: There is some evidence for the
effectiveness of multiple public health interventions on food safety. Future
research needs include evaluation of HACCP and community-based education
programs.
PMID- 9654808
TI - Influences on breastfeeding rates in low income communities in Ontario.
AB - The purpose of this paper was to identify factors associated with breastfeeding
among mothers of children born in 1994 in five of the low income communities
participating in the longitudinal prevention initiative "Better Beginnings,
Better Futures." Household income was < or = poverty line for 76%, 63% had
completed high school or beyond, and 29% were born outside of Canada. The
breastfeeding initiation rate was 77% (380 of 493). Of the 270 women who
initiated breastfeeding and were interviewed up to five months postpartum, 63%
continued for at least three months. Women with higher education, married, not
experiencing financial stress and who attended prenatal classes were more likely
to initiate breastfeeding. Continuation of breastfeeding was associated with
older age, higher education, not smoking, and participation in a home visitor
program. Breastfeeding promotion strategies should include ongoing support as
well as education components.
PMID- 9654809
TI - Socioeconomic position. Lifestyle and health among Canadians aged 18 to 64: a
multi-condition approach.
AB - Although a sizeable literature documents the link between socioeconomic position
and health in Britain and the United States, much less work has been conducted in
Canada. Moreover, what work has been done has been limited to single outcomes
such as self-rated health or age-adjusted mortality. Very little has been
conducted using multiple health outcomes, although doing so has been advocated.
Using the 1991 General Social Survey on Health, we extended an earlier analysis
to explore whether or not "condition-specific" relationships exist between
socioeconomic position, lifestyle, and health among working age Canadians. We
distinguished four patterns in terms of education and income adequacy. The
effects of occupation did not fit into any simple pattern. Measures of lifestyle
appear to mediate the relationship between education and morbidity, but not
between income adequacy and morbidity. Findings are discussed in terms of the
theoretical, methodological and policy implications of a condition-specific
approach.
PMID- 9654810
TI - Hope suspended: morality, politics and war in central Africa.
AB - The Great Lakes tragedy from 1994-8 has demonstrated the impact of a new
consensus in favour of conditional relief for the protection and assistance of
disaster victims. This paper attempts to catalogue the failures of the
international humanitarian community, African leaders and donor governments to
act effectively in defence of humanitarian principles throughout the crisis. The
paper places special emphasis on the events in eastern Zaire during 1996-7 that
have, so far, received limited treatment, and, it contends, led to the loss of
hundreds of thousands of lives. The paper argues that the new orthodoxy of
developmental relief, as adopted by UN and NGO humanitarian agencies in the Great
Lakes, has acted more in support of the geopolitical and economic agendas of
Northern governments and African leaders than in defence of disaster victims. The
paper points out that the evidence of the Great Lakes tragedy suggests that the
adoption of these approaches has sanctioned the abandonment of ideas about
universal rights of protection for non-combatants at the moment when they are
most at risk, with catastrophic results for those most vulnerable to abuse.
PMID- 9654811
TI - Cool ground for aid providers: towards better security management in aid
agencies.
AB - Although full statistics are lacking, there is an impression that aid personnel
are increasingly at risk from random, criminal and even at times targeted
violence. The argument here is that the current tendency to reduce an agency's
vulnerability mainly through the use of protective procedures and devices may be
necessary but is insufficient. Better practice in the management of security is
an urgent need. Reducing vulnerability to attack is only one approach; deterring
the threat of violence by counter-threat, or seeking increased acceptance for the
agency's work and presence are two other approaches. Major skill development is
required in the areas of conflict analysis and monitoring, threat assessment and
incident analysis, since together these form the basis for appropriate security
management. Improved analysis can then inform a conscious choice about which
mixture of approaches is most appropriate in a specific context. The paper
explores in some detail the factors that influence acceptance, but not the
methods and basic principles in the use of counter-threat.
PMID- 9654812
TI - Making women visible in disasters: problematising the private domain.
AB - Gender awareness and sensitivity in disaster research and management remains
uncommon and tends to focus on the developing rather than the developed world.
This paper uses a feminist oral geography to present some findings about women's
experiences in two floods in Scotland. It is conceptualised around public and
private (masculinised and feminised) space, problematising the private domain and
presenting it, in the feminist research tradition, as a legitimate object of
research. It shows the ordinary and everyday to be more opaque and complex than
usually imagined and makes recommendations for their recognition and
incorporation into disaster management. While there is a specific focus on the
private domain of the home, this is not intended to reinforce gender stereotypes
but simply to recognise the reality of many of the women interviewed. It
concludes that disaster research generally has yet to advance much beyond the
earliest stages of feminist studies which merely sought to make women visible in
society.
PMID- 9654813
TI - A review of contributions to disasters: 1977-1996.
AB - Since the first issue in 1977. Disasters has been one of the pre-eminent refereed
journals on the study and reporting of disasters. This article reviews 703
articles and reports in the journal through 1996 to provide a snapshot of the
nature of the journal throughout 20 years of publication. The results indicate
the most common contributions: first, were research articles by authors from the
North Atlantic; second, most often dealt with natural disaster relief or impact;
and third, most frequently focused on Africa. These generalisations, however, do
not reflect attention paid to food-related and political disasters and greatly
understate the broad diversity of material presented in the journal. To improve
the topical and geographic coverage of Disasters probably requires a proactive
effort to close gaps in the journal's coverage of disasters.
PMID- 9654814
TI - Through women's eyes: a gendered research agenda for disaster social science.
AB - Gender is a central organising principle in social life and hence in disaster
affected communities, yet gender issues are rarely examined by disaster scholars
or practitioners. Building on findings from emerging and industrial nations,
three key research directions are identified: How is gendered vulnerability to
disaster constructed? How do gender relations shape the practice of disaster
planning and response in households and organisations? How are gender relations
affected over time by the social experience of disaster? The discussion suggests
how analysis of the gendered terrain of disaster both develops disaster theory
and fosters more equitable and effective disaster practice.
PMID- 9654815
TI - The disaster-to-development continuum.
PMID- 9654816
TI - Lung volume reduction surgery.
PMID- 9654817
TI - Clinical presentation of tuberculosis in patients with AIDS: an Indian
experience.
AB - A retrospective series of 25 patients with AIDS and tuberculosis is presented.
Their clinical presentation, absolute lymphocyte count, CD4+ and CD8+ lymphocyte
counts, treatment details and outcome are detailed. Commonest method of acquiring
HIV infection was through heterosexual contact (10 of the 25; 40%) and blood
transfusion (10 of the 25; 40%). More than 50% of the patients (14 of the 25) had
extrapulmonary tuberculosis. Eighteen of the 19 patients for whom values were
available had CD4+ lymphocyte count < 200/mm3. Four of the 18 patients for whom
follow-up details were available died.
PMID- 9654818
TI - Bronchial carcinoid tumours in southern Saudi Arabia.
AB - Clinical presentation, pathology, surgical management and follow-up of ten
bronchial carcinoid tumour (BCT) patients are described. There were five male and
five female patients with age range between 5 to 85 years (mean 39.2 +/- 21.5,
SD). Pathology revealed BCT on the right side in seven and on left side in three
patients. The tumour was an incidental finding in four while the other six had
respiratory symptoms. Cough was present in all of the later group and hemoptysis
was present in four patients. Recurrent chest infections were seen in two
patients. Symptoms ranged from 1 week to 15 years. Successful surgical resection
was done in nine with the longest follow-up of 80 months (mean: 23 months +/-
26.3, SD) without recurrence or metastasis. Histopathological examination of
these tumours revealed classical morphological features in all but one case.
Grimelius stain positivity for argyrophilia confirmed the diagnosis in all the
patients in this study. Electron microscopic examination was done in patient no.
9 which showed atypical morphological features and neurosecretory granules. BCT
may present like pneumonias or bronchial asthma. Although BCTs have low-grade
malignancy, early diagnosis and surgical resection yield curative results almost
in all cases.
PMID- 9654819
TI - Mediastinal bronchogenic cysts.
AB - It was observed from the literature that the incidence, clinical and radiological
features of the mediastinal bronchogenic cysts are different in adults than in
infant population. Five cases of bronchogenic cysts in the middle mediastinum
were studied over a period of 22 years. The cysts were carina-based in four cases
and paratracheal in one case. The airway compression was observed in four cases
due to cysts. In case one the cyst compressed the right pulmonary artery and vein
as well as both mainstem bronchi causing their stenosis and bulged into the left
atrial chamber.
PMID- 9654820
TI - An analysis of effect of common domestic fuels on respiratory function.
AB - Pulmonary function studies were carried out in 3318 healthy, nonsmoking
asymptomatic housewives to evaluate the role of different cooking fuels in
domestic use. The women used four different types of cooking fuels: biomass fuel,
liquified petroleum gas (LPG), kerosene used in stoves, and a combination of two
or more of these (mixed). Four parameters of ventilatory function (FVC, FEV1,
PEFR and MMEF) were evaluated. A positive correlation was observed between all
these parameters except PEFR with that of height, but a negative correlation was
observed between the age, duration of cooking and exposure index. Mixed fuels and
biomass fuels affected FVC values (F = 6.39, p = 0.0003) more adversely. Similar
trend was observed for FEV1 also. Users of biomass fuel had the lowest mean value
for PEFR. Small airways function represented by MMEF was the lowest in users of
kerosene. In users of mixed fuels, there was a decline in FVC, FEV1 and PEFR, as
the exposure increased. Thus, it is concluded that, mixed fuel has more
deleterious effects on pulmonary function than other fuels.
PMID- 9654821
TI - Bilateral miliary pattern in sarcoidosis.
PMID- 9654822
TI - Endobronchial tuberculosis simulating lung cancer.
AB - We describe an atypical presentation of endobronchial tuberculosis in a 45-year
old female who presented to us with a non-resolving pneumonia. Her radiological
examination including contrast enhanced CT-scan suggested a diagnosis of
bronchogenic carcinoma or adenoma. Gross bronchoscopic finding also favoured
malignancy. But her bronchoscopic biopsy revealed caseating granulomatic lesion.
She responded to antitubercular treatment.
PMID- 9654823
TI - Acute isoniazid poisoning: presenting as seizure.
AB - A case of young female who was brought in status epilepticus with history of
isoniazid poisoning is discussed. Early institution of treatment with pyridoxine
saves the patient's life.
PMID- 9654824
TI - Non-Hodgkin's lymphoma masquerading as empyema thoracis.
AB - Non-hodgkin's lymphoma has varied presentations. Malignant lymphoma arising in
chronic pyothorax is very rare and has been reported from Japan. We report a case
of non-hodgkin's lymphoma presenting as empyema thoracis.
PMID- 9654825
TI - Pulmonary alveolar microlithiasis: diagnosed by sputum examination and
transbronchial biopsy.
AB - A case of pulmonary alveolar microlithiasis presenting with uncharacteristic
radiological features who was diagnosed on the basis of sputum examination and
confirmed by transbronchial biopsy, is being reported. Azoospermia resulting in
primary infertility and increased lung volumes by helium dilution test were other
noteworthy features of the case.
PMID- 9654826
TI - Antibiotic use for infective terminal respiratory secretions.
PMID- 9654827
TI - Re: Cancer pain emergencies.
PMID- 9654828
TI - Antiemetic efficacy of subcutaneous 5-HT3 receptor antagonists in terminal cancer
patients.
PMID- 9654829
TI - Thioridazine in the management of cancer-related sweating.
PMID- 9654830
TI - Re: A randomized controlled trial of Intravenous clodronate.
PMID- 9654831
TI - Dextropropoxyphene acts as a noncompetitive N-methyl-D-aspartate antagonist.
AB - In order to elucidate whether opioid analgesics available on the Scandinavian
market also act as noncompetitive N-methyl-D-aspartate (NMDA) antagonists, a
series of commercially available opioids were screened for their affinity in
[3H](RS)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine ([3H]MK
801) binding assays and potential inhibitory actions on responses to NMDA in the
rat cortical wedge preparation. Of the screened compounds (codeine,
dextropropoxyphene, etorphine, fentanyl, and morphine), only dextropropoxyphene,
with an IC50 value in [3H]MK-801 binding of 5 microM, was found to be active.
Further characterization of the interaction of dextropropoxyphene with the NMDA
response in the rat cortical wedge preparation illustrated the noncompetitive
NMDA antagonist activity of dextropropoxyphene. Analysis of the
dextropropoxyphene inhibition curve of NMDA gave an IC50 value of 190 microM and
a Hill slope of 0.8.
PMID- 9654832
TI - Cancer pain survey: patient-centered issues in control.
AB - It is widely believed that patients' reluctance to report pain and adhere to
treatment recommendations are significant barriers to cancer pain control.
However, few investigators have examined barriers to cancer pain management from
the cancer patient's perspective. Ambulatory patients with cancer who had
experienced cancer-related pain in the previous month or were currently taking
analgesics for cancer pain control were asked to participate in this study.
Information regarding (a) pain assessment, (b) pain medication use, (c) concerns
and barriers to compliance, (d) communication patterns regarding pain and pain
control, and (e) demographics were collected during a 10-min structured
interview. Approximately 20% of patients with a current cancer diagnosis who were
approached reported that they had experienced pain or taken analgesic drugs
during the preceding month. Eighty-eight percent of these patients ranked their
pain as five or greater (scale, 0-10), and 81% reported impaired function due to
pain. Major barriers to effective treatment included forgetfulness, the belief
that pain should be tolerated, concerns about side effects, and fear and disdain
of dependence, addiction, and tolerance. One-third of patients felt that their
pain could not be better controlled than it currently was. Patients reported
frequent communication regarding pain and pain control with physicians (52%),
nurses (41%), and pharmacists (17%). The low pain prevalence, coupled with high
pain intensity and associated dysfunction, appears to be a reflection of
patient's unwillingness to report pain of mild to moderate intensity. In addition
to previously recognized factors, stoicism and fatalism represent significant
barriers to cancer pain control.
PMID- 9654833
TI - The prevalence and severity of cancer pain: a study of newly-diagnosed cancer
patients in Taiwan.
AB - Cancer pain is a relatively neglected public health issue in Taiwan. To
characterize the nature of this problem, interviews were conducted on newly
diagnosed cancer patients admitted to the Tri-Service General Hospital during a
period of 18 months. Data were collected on the prevalence and severity of cancer
pain, its treatment, and impact on patients in the week before the interview.
Correlates of prevalence and severity of cancer pain were also examined. The
final analysis included 296 patients who had no history of recent surgery. Most
of the patients (69%) were interviewed within 14 days of their definitive
diagnosis of cancer. Thirty-eight percent (N = 113) of the patients had cancer
related pain. Of these 113 patients, 65% had "significant worst pain" (worst pain
level at or above five on a ten-point scale) and 31% had "significant average
pain" (average pain level at or above five most of the time); 69% received no
pain medication at all or inadequate medication (not "by the ladder"), and 23%
had pain medication that was not administered at a fixed interval (not "by the
clock"). Multivariate analyses showed that cancer pain was more prevalent in non
Mainlanders, those with a lower level of insurance, those with a history of
excellent pain tolerance, those with poor Eastern Cooperative Oncology Group
(ECOG) performance status, and those with distant metastases. Patients who were
at greater risk of "significant worst pain" were those with regional or distant
metastases, those in whom an inadequate analgesic medication had been prescribed
(not "by the ladder"), and those who had received an appropriate analgesic
medication but no fixed schedule dosing ("by the ladder" but not "by the clock").
Patients who were at greater risk of "significant average pain" were those not
undergoing any resection of the tumor lesion and those who received an
appropriate drug but no fixed schedule dosing ("by the ladder" but not "by the
clock").
PMID- 9654834
TI - Development of a short version of the Barriers Questionnaire.
AB - Among the reasons that cancer pain is not controlled adequately are patient
related barriers. Patient beliefs that may contribute to poor outcome have been
measured in previous research with the Barriers Questionnaire (BQ). The purpose
of this study was to examine the internal consistency of a shortened version of
the BQ. A sample of 217 outpatients with cancer completed a 17-item version of
the scale. Factor analysis suggested two subscales, one reflecting beliefs about
communication about pain and the other reflecting beliefs about the use of
analgesics. Both subscales demonstrated adequate internal consistency. Beliefs
did not differ between patients who had and those who had not experienced pain
within the previous two weeks. Findings suggest the shortened BQ provides an
internally consistent measure of two broad patient barriers to pain management.
PMID- 9654835
TI - Drug infusors in palliative medicine: a Swedish inquiry.
AB - The use of drug infusors is common in palliative care. Knowledge about the drugs
being used and the handling of drug mixtures in insufficient and poorly
documented. To clarify this practice, a questionnaire was sent to all departments
of pain/anesthesiology and oncology, and to all home-care teams and palliative
care units/hospices in Sweden (N = 156). The questions concerned specific
qualities of the drug infusors and the different drugs and drug mixtures used by
subcutaneous (s.c.) and intravenous (i.v.) administration. A total of 110 (70%)
of the questionnaires were returned. A majority of the respondents reported the
use of one or more of three different infusors. Morphine was used in 73% of all
single drug infusions. Dosages ranged from 30 mg/24 hr to 5000 mg/24 hr. The most
common drug mixture was morphine/haloperidol (22% of all drug mixtures). As many
as three drugs were used in combination. The most frequent indication to switch
from oral administration to parenteral administration was gastrointestinal
disorders such as swallowing difficulties, nausea, vomiting, or bowel
obstruction. In Sweden, there is extensive clinical experience administering
opioids in infusors, but experience varies for different drug mixtures. There are
few clinical and pharmacological investigations to support this practice and
further studies are needed.
PMID- 9654836
TI - Pain and fear ratings: clinical implications of age and gender differences.
AB - The study investigated the relationships among children's self-report of
anticipatory pain and fear, physiological measures of distress, and previous
medical experience in 62 outpatients during allergy skin testing. Younger (aged 3
7 years) and older (aged 8-12 years) children reported similar amounts of pain
and fear. Girls reported more pain than boys. Older children and boys provided
differential pain and fear ratings compared with younger children and girls.
Younger children's self-report of distress was not related to any physiological
measures, but older children's report of fear was significantly related to blood
pressure. In girls, positive medical experience was correlated with less pain.
The implications of these findings for the clinical measurement and intervention
of children's distress during painful medical procedures are discussed.
PMID- 9654837
TI - Proglumide as a morphine adjunct in cancer pain management.
AB - Proglumide, a cholecystokinin (CCK) antagonist, has been shown to have agonist
effects at extremely low doses on both endogenous and exogenous opioid systems.
To determine the effectiveness and the side effects of proglumide as an opioid
agonist, a double-blind crossover study was conducted in 60 patients with cancer
pain who were treated with opioid analgesics. Forty-three patients completed both
treatment arms: (a) full analgesic dose plus placebo (the patient's usual
analgesic dose, individualized to drug dose and route) and (b) one-half analgesic
dose plus 50 mg of proglumide. An analysis of eight pain descriptors was
performed to determine whether or not these treatments were associated with a
difference in patients' pain perception. The level of patient anxiety differed
between the two arms, but was inconsistent over time. There were no side effects
detected with proglumide, as determined by clinical monitoring and patient
questionnaire. No differences in pain perception were detected between the study
arms. The latter finding is consistent with an augmentation of morphine
analgesia, but without additional controls, the equivalency of the two arms
cannot be determined with certainty. Nonetheless, this study suggests that
proglumide may have use as an opioid adjunct in patients with cancer pain.
PMID- 9654838
TI - Spinal accessory nerve palsy as a cause of pain after whiplash injury: case
report.
AB - Spinal accessory nerve injury is most commonly reported following surgery in and
around the posterior cervical triangle. Pain, impaired ability to raise the
ipsilateral shoulder, and scapular winging on abduction of the arm are the most
frequently noted clinical manifestations. We report the case of a collegiate
swimmer who developed left-sided neck and shoulder pain secondary to a spinal
accessory nerve palsy (SANP) after a "whiplash injury," which we believe to be
the first such reported case in the English language literature. We review the
clinical manifestations, diagnostic pitfalls, and therapeutic approaches to SANP.
A high index of suspicion for SANP following whiplash-type injury will ensure its
earlier detection and treatment and improve the chances of a better functional
outcome.
PMID- 9654839
TI - FDA reform: implications for health economic research and pharmacy practice.
PMID- 9654840
TI - Do we really need quality measures in community pharmacy?
PMID- 9654841
TI - Computerized DUR alerts: boon or bane to pharmaceutical care?
PMID- 9654842
TI - Medical marijuana: not the way the doctor would have ordered it.
PMID- 9654843
TI - Medicinal marijuana: the California experiment.
PMID- 9654844
TI - Integrated pharmacy services: cornerstone of a new model of care at celebration
health.
PMID- 9654845
TI - Pharmacy Practice Activity Classification.
PMID- 9654846
TI - How pharmacists respond to on-line, real-time DUR alerts.
AB - OBJECTIVE: To quantify the type and frequency of drug utilization review (DUR)
alerts sent by one claims processor to pharmacists; identify how pharmacists
respond to these on-line, real-time DUR messages; and quantify the interventions
taken by these pharmacists as a result of these alerts. DESIGN: Retrospective
analysis of Medicaid claims from July 1, 1995, through June 30, 1996. SETTING:
State of Delaware. PARTICIPANTS: 55,000 Medicaid recipients served by 170
participating pharmacies and 2,000 physicians. INTERVENTIONS: All on-line DUR
alerts sent to pharmacists and the pharmacists' responses were categorized by
alert type and analyzed by drug class. MAIN OUTCOME MEASURES: Pharmacists'
response (dispensed prescription, contacted prescriber, talked with patient,
consulted own reference sources) and drug classes. RESULTS: During the study
period, 807,017 claims generated 83,260 DUR alerts involving 73,554 (9.1%)
prescriptions. Prescriptions were not dispensed in 20.9% of cases because of the
DUR message. Prescriptions were dispensed 17.7% of the time after the pharmacist
contacted the prescriber, in 20.6% of cases after the pharmacist talked with the
patient, and 37.2% of the time after reviewing internal resources. Action taken
by pharmacists varied among and within DUR criteria categories. Specific examples
of alerts generated in high-frequency and high-profile areas are reviewed, some
of which generated inconsistent responses. CONCLUSION: Among Delaware Medicaid
providers, drug alerts resulted in pharmacists not dispensing prescriptions in a
surprising percentage of situations. Pharmacists' responses varied according to
the drug class involved and the type of alert received.
PMID- 9654847
TI - New drugs of 1997.
AB - OBJECTIVE: To provide information regarding the most important properties of the
new therapeutic agents marketed in 1997. DATA SOURCES: Published studies, drug
information reference sources, and product labeling. DATA SYNTHESIS: A record
setting number of 45 new therapeutic agents were marketed in 1997. The
indications and information on dosage and administration for each new agent are
reviewed, as are the most important pharmacokinetic properties, adverse events,
drug interactions, and other precautions. Practical considerations for the use of
the new agents are also discussed. Where possible, the properties of the new
drugs are compared with those of older drugs marketed for the same indications.
CONCLUSION: A number of the new therapeutic agents marketed in 1997 have
important advantages over older medications. An understanding of the properties
of these agents is important for the pharmacist to effectively counsel patients
about their use and to serve as a valuable source of information for other health
professionals regarding these drugs.
PMID- 9654848
TI - New OTC drugs and devices 1997: a selective review.
AB - OBJECTIVE: To create a heightened awareness of the proposals for nonprescription
product labeling changes being explored by the Food and Drug Administration and
the Nonprescription Drug Manufacturers Association, and to review selected new
self-care products that are now available in the United States. DATA SOURCES:
Recent clinical and pharmaceutical industry literature. DATA SYNTHESIS: The
debate continues about what constitutes sufficient labeling information for a
nonprescription drug product. However, one fact remains. Numerous nonprescription
drug products, including home diagnostic products and accessories, will continue
to become available on the U.S. market. It is important that the pharmacist
become as knowledgeable as possible about these products, and be capable of
educating consumers on their appropriate use. CONCLUSION: New products cited in
this review article are valuable new additions to the self-care product pool that
provides an increasing array of products for consumer use.
PMID- 9654849
TI - Important features of blood glucose meters.
AB - OBJECTIVE: To provide an overview of several blood glucose meters that will
enhance practicing pharmacists' knowledge and understanding of these devices to
allow education of the patient with diabetes. DATA SOURCES: Original and review
articles, blood glucose meter package inserts and manuals. DATA SYNTHESIS:
Careful blood glucose control is essential to prevent long-term complications of
diabetes. Newer blood glucose meters have a broad variety of features, including
small size, extended memory capacity, blood glucose manipulation techniques, and
computer downloading capabilities. The decision to choose a blood glucose meter
should be based on a number of criteria, including the patient's needs, ease of
use, and affordability. CONCLUSION: Pharmacists must position themselves to
differentiate among the numerous blood glucose meters available on the market and
make appropriate recommendations based on patient-specific needs.
PMID- 9654850
TI - Analysis of the medical use of marijuana and its societal implications.
AB - OBJECTIVE: To review the pharmacology, therapeutics, adverse effects, and
societal implications of the medical use of marijuana. DATA SOURCES: MEDLINE and
manual searches of English-language marijuana literature, supplemented with
interviews of scientists currently conducting cannabinoid research. Search terms
included pain OR palliative care AND cannabis or ALL marijuana; cachexia OR
appetite OR appetite stimulants; muscle spasticity OR spasm; immune system and
cannabis; nausea and vomiting and cancer and cannabis. MEDLINE search terms:
cannabis OR marijuana smoking OR marijuana abuse; all glaucoma; multiple
sclerosis AND cannabis OR marijuana smoking OR marijuana abuse. STUDY SELECTION:
Studies on pharmacology, risks, and medical potential of marijuana. DATA
EXTRACTION: Not applicable. DATA SYNTHESIS: The most prominent effects of
marijuana are mediated by receptors in the brain. Acute intoxication is
characterized by euphoria, loss of short-term memory, stimulation of the senses,
and impaired linear thinking. Depersonalization and panic attacks are adverse
effects. Increased heart rate and reddened conjunctivae are common physical
effects. Chronic, high doses may cause subtle impairment of cognitive abilities
that are appear to be long-term, but of unknown duration. Marijuana may be a risk
factor for individuals with underlying mental illness. It causes dependence, but
compared with cocaine, alcohol, heroin, and nicotine, marijuana has little
addictive power and produces only mild withdrawal symptoms. Marijuana shows
clinical promise for glaucoma, nausea and vomiting, analgesia, spasticity,
multiple sclerosis, and AIDS wasting syndrome. CONCLUSION: As a recreational
drug, marijuana poses dangers, particularly to social and emotional development
during adolescence and young adulthood. As a medical drug, marijuana should be
available for patients who do not adequately respond to currently available
therapies.
PMID- 9654851
TI - Melatonin and sleep: a balanced view.
PMID- 9654852
TI - Pharmacoeconomics of biotechnology drugs (2).
PMID- 9654853
TI - Pharmacists as self-care consultants.
PMID- 9654854
TI - Immunizations after influenza season: focus on pneumococcal disease.
PMID- 9654855
TI - Medical information on the Internet: fool's gold or 24 karat?
PMID- 9654856
TI - Nelfinavir and nevirapine.
PMID- 9654857
TI - Team approach to HIV exposures.
PMID- 9654858
TI - Using protocols in the context of pharmacists' patient care responsibilities.
PMID- 9654859
TI - Creating expectations: a first step toward pharmacist-patient confidentiality.
PMID- 9654860
TI - New schools strive to carve their own niche in pharmacy education.
PMID- 9654861
TI - APhA drug treatment protocols: management of gestational diabetes mellitus and
impaired glucose tolerance during pregnancy. APhA Diabetes Mellitus Panel.
PMID- 9654862
TI - System for exchanging information among pharmacists in different practice
environments.
AB - OBJECTIVES: A system for exchanging patient information among hospital, long-term
care (LTC), and ambulatory care pharmacies is described, and the influence of
that system on pharmacist interventions is reported. METHODS: Study sites
consisted of three ambulatory care pharmacies, one LTC pharmacy, and one hospital
in a small Midwestern city. Meetings were held by clinicians, the investigators,
and hospital administrators to plan the information-exchange system. From January
through June 1996, patients admitted to the hospital were checked to see if they
came from a participating (source) pharmacy; if so, they were randomly assigned
to experimental and control groups. The hospital requested preadmission
information from the source pharmacy for experimental group patients and did not
do so for control patients. After the information arrived, the hospital
pharmacists could use it to identify and document drug therapy problems. When an
experimental group patient was discharged, the hospital sent information to the
appropriate source pharmacy. A total of 156 patients were enrolled in the study.
RESULTS: Complete information transfer occurred for 75% of experimental group
patients. Significantly more experimental group patients than control patients
had at least one in-hospital pharmacist intervention recorded. Similarly, in the
ambulatory care pharmacies (but not the LTC pharmacy) significantly more
interventions per patient were documented for the experimental group. CONCLUSION:
Hospital and ambulatory care pharmacists documented more interventions for
patients about whom information had been supplied than for patients for whom that
information had not been supplied. No difference in intervention rates was
observed for LTC pharmacists, who were already being supplied information by the
LTC facilities about patients discharged from the hospital.
PMID- 9654863
TI - Comparison of targeting a DUR letter intervention at pharmacists separate from
and in addition to physicians.
AB - OBJECTIVE: To examine the impact on dipyridamole prescribing of a letter mailed
to pharmacists and/or physicians. DESIGN: Interrupted time series with control
series. SETTING: State of Wisconsin. PARTICIPANTS: Physicians and pharmacists
caring for patients who were prescribed dipyridamole. INTERVENTIONS: The state of
Wisconsin was divided into four sections, three of which were designated as
experimental regions (letter to physician only, letter to pharmacist only, and
letter to both physician and pharmacist) and one of which served as a control
region. MAIN OUTCOME MEASURES: Cost of drug per patient per month in ambulatory
and long-term care populations. RESULTS: For 763 long-term care and 586
ambulatory Medicaid patients, letters sent to both physicians and pharmacists
resulted in significant reductions in dipyridamole expenditures relative to the
control group. For long-term care patients, interventions directed at both
physicians and pharmacists produced significant reductions in dipyridamole
prescribing relative to interventions directed at physicians alone or pharmacists
alone. CONCLUSION: Future DUR letter interventions designed to change prescribing
habits would be more effective if they targeted both physicians and pharmacists,
particularly in the long-term care setting.
PMID- 9654864
TI - Michigan Medicaid recipients' perceptions of medication counseling as required by
OBRA '90.
AB - OBJECTIVE: To assess pharmacist counseling under OBRA '90 from the Medicaid
recipient's perspective. Specifically, the study was designed to (1) assess
pharmacists' compliance with counseling requirements, (2) assess recipients'
level of satisfaction with the information provided during counseling and whether
the information provided increased their comfort level in taking medication
correctly, and (3) determine relationships between variables associated with
pharmacist counseling and recipient satisfaction and comfort level. DESIGN: Cross
sectional telephone survey of Medicaid recipients. Medicaid recipient or
caregiver was the unit of measure. SETTING: Michigan. PATIENTS: 408 recipients
who received new prescriptions during a one-week period in November 1995.
INTERVENTIONS: Telephone survey. MAIN OUTCOME MEASURE: Recipients' perception of
whether an offer to counsel was made. RESULTS: Only 104 (25.5%) recipients
indicated that someone offered counseling for their new prescription, and only 62
(15.2%) recipients indicated they knew of the requirement; 163 (40.0%) indicated
someone offered counseled them. Counseled recipients were satisfied with the
amount, quality, and way the information was presented, and were more likely to
assign a higher level of importance to pharmacist counseling. The majority of
respondents indicated high levels of comfort in using their medications safely,
with those who were counseled expressing a higher level of comfort. CONCLUSION:
From the perspective of the Medicaid recipient, pharmacies are failing to offer
counseling for most new prescriptions. The results indicate that counseling
improves measures of recipient comfort in using medications safely and enhances
the level of importance patients assign to pharmacist counseling.
PMID- 9654865
TI - Smoking cessation: Part 2--Pharmacologic approaches.
AB - OBJECTIVE: To present the concept of nicotine-replacement therapy (NRT) and the
pharmacologic approaches, nonprescription and prescription, to smoking cessation.
DATA SOURCES: Current clinical literature. DATA SYNTHESIS: NRT can be delivered
through a number of different nicotine-containing dosage forms (e.g., gum, patch,
nasal spray, oral inhaler). The Agency for Health Care Policy and Research
(AHCPR) recommends using the nicotine patches for routine clinical practice and
the American Psychiatric Association (APA) recommends the use of the patches and
gum as initial pharmacotherapies for smoking cessation. There are no comparative
studies indicating the superiority of one form or another at relieving nicotine
withdrawal symptoms. Of the other pharmacologic agents used for smoking
cessation, bupropion hydrochloride demonstrates the most promise. CONCLUSION: The
pharmacist can assist the consumer with the selection of an OTC smoking cessation
product and serve as an informational resource to consumers and physicians
desiring information on prescription drug products for smoking cessation.
PMID- 9654867
TI - Gestational diabetes.
AB - OBJECTIVE: To review the detection, diagnosis, and clinical management of
gestational diabetes. DATA SOURCES: MEDLINE, Gestational Diabetes Guideline
Review, 1968-1998. STUDY SELECTION: By the author. DATA EXTRACTION: By the
author. DATA SYNTHESIS: Gestational diabetes is a common complication of
pregnancy, occurring in 2% to 6% of pregnancies. Uncontrolled gestational
diabetes is associated with increased infant morbidity and mortality, macrosomia,
and cesarean deliveries, and is a strong marker for the future development of
maternal diabetes mellitus. Women with risk factors for gestational diabetes
should be screened for glucose intolerance at 24 to 28 weeks' gestation. If a
screening plasma glucose concentration is 140 mg/dL or greater one hour after a
50 gram oral glucose load, then a diagnostic 100 gram, three-hour oral glucose
tolerance test should be performed. Medical nutrition therapy is the cornerstone
of management and must be designed to meet individual needs. Self-monitoring of
blood glucose should be taught to and performed by all women with gestational
diabetes. Insulin, which does not readily cross the placental barrier, is the
drug therapy of choice in women failing medical nutrition therapy. CONCLUSION:
Pharmacists can optimize overall care by educating, monitoring, and intervening
or assisting the patient in the management of gestational diabetes.
PMID- 9654866
TI - The role of pharmacy in the management of patients with temporomandibular
disorders and orofacial pain.
AB - OBJECTIVE: To provide information regarding the current understanding of the
etiology and treatment, both nonpharmacologic and pharmacologic, of orofacial
pain conditions including temporomandibular disorders (TMDs). This review briefly
discusses the etiology and pathophysiology underlying the development of TMDs,
generally accepted nonpharmacologic methods of treatment, and the most common
current pharmacologic management approaches. DATA SOURCES: Current medical
literature and the authors' clinical experiences. DATA SYNTHESIS: TMDs encompass
a number of diagnostic subgroups that involve the masticatory musculature, the
temporomandibular joint(s), and associated structures. More than 10 million
individuals in the United States are affected by TMDs. Most current pharmacologic
management approaches in the treatment of orofacial pain conditions, including
TMDs, involve the use of antidepressants, anticonvulsants, muscle relaxants,
corticosteroids, and nonsteroidal anti-inflammatory drugs. CONCLUSION: Inclusion
of pharmacists who are knowledgeable in the nonpharmacologic and pharmacologic
treatment approaches on the TMD management team would improve therapeutic
monitoring, follow-up, and outcomes in these patients.
PMID- 9654868
TI - Pharmacist-patient privilege, confidentiality, and legally-mandated counseling: a
legal review.
AB - OBJECTIVE: To indicate the necessity for uniform, privileged status of pharmacist
patient communications. DATA SOURCES: Published cases (LEXIS), literature (NEXIS
and MEDLINE), and abstracts available through November 1997. CASE SELECTION AND
DATA ABSTRACTION: Selected by the authors for inclusion based on objectives,
publication in English, and usefulness of information for practicing pharmacists.
DATA SYNTHESIS: Since pharmacists are now legally required to counsel patients
under federal and state laws, protection of the confidentiality of such
information is of concern. Statutes are largely silent on the issue of pharmacist
patient communications, particularly oral communications. Some states recognize
privilege (protection from subpoenas and court orders), others provide
confidentiality only (information must be divulged only upon subpoena or court
order), and most states specify neither type of protection for pharmacist-patient
communications. An evaluation of case law indicates personal and legal risks, for
both pharmacist and patient, associated with unprivileged communications
occurring within a counseling situation. CONCLUSION: Pharmacist-patient
communications must be granted privileged status, in all states, to protect both
pharmacist and patient if pharmacists are to fulfill their legally-mandated
counseling responsibilities.
PMID- 9654869
TI - New therapeutic monoclonal antibodies target kidney transplant rejection and
cancer.
PMID- 9654870
TI - Susceptible to tetanus and diphtheria? Immunize against both.
PMID- 9654871
TI - On-line learning: trends in continuing education.
PMID- 9654872
TI - A collective review of the world literature on hepatic cryotherapy.
AB - Published results of hepatic cryotherapy are now available for almost 900
patients. Its safety is well established and its clinical role in treating
patients with unresectable hepatoma or liver metastases from colorectal carcinoma
is well supported by tumour marker and survival data; the results in the
treatment of neuroendocrine liver metastases are promising. Its role as an
alternative to liver resection is not yet well supported by long-term data.
Although different adjuvant treatment protocols have been used following the
cryotherapy of colorectal liver metastases, the effect of adjuvant treatment on
recurrence or survival has not been assessed in prospective studies. Laparoscopic
hepatic cryotherapy is feasible in selected patients with suitable tumour
locations. However, the proportion of patients who might be usefully treated with
this technique is not yet well established. The mechanisms of tissue destruction
by freezing are reviewed.
PMID- 9654873
TI - Thrombogenicity of heparin and non-heparin bound arterial prostheses: an in vitro
evaluation.
AB - The effect on graft thrombogenicity of binding heparin to the luminal surface of
prosthetic arterial grafts was investigated. Venous blood was obtained from
healthy volunteers and exposed for 30 minutes to tubular segments of standard
knitted dacron, polytetrafluoroethylene (PTFE) and a recently introduced heparin
bound knitted dacron graft. After this exposure the fibrinogen level of each
sample was measured. The median (range) fibrinogen levels (expressed as a
percentage of that in unexposed blood samples) were: standard dacron 3.5% (0
5.4%); PTFE 95.5% (0-121.1%); and heparin-bound dacron 79.8% (3.8-109.6%).
Fibrinogen levels in the standard dacron group were significantly less than that
of the PTFE and heparin-bound dacron groups (P < 0.05). No significant difference
was found between the fibrinogen levels of the PTFE and heparin-bound dacron
groups (P = 0.35). These findings suggest that heparin binding significantly
reduces fibrinogen consumption and hence may reduce graft thrombogenicity.
PMID- 9654874
TI - Effectiveness of topical non-steroidal anti-inflammatory drugs in the management
of breast pain.
AB - A prospective study of the effectiveness of the topical application of non
steroidal anti-inflammatory drugs (NSAIDs) as a gel preparation was carried out
in 26 women with severe breast pain. The results showed a satisfactory relief of
pain in 81% of the women: 11 of 13 with cyclical pain, eight of 11 with non
cyclical pain, and in two women with severe scar pain after lumpectomy and
radiotherapy. Topical NSAID gel was applied as required; the relief of severe
pain was rapid and no side effects were reported. These factors compare
favourably with established recommended treatments which usually involve months
of continuous treatment, tailoring of drug dosages and a significant incidence of
intolerable side effects. This study has shown that topical NSAID application is
an effective, safe, acceptable and easily administered treatment for severe
cyclical and non-cyclical breast pain.
PMID- 9654875
TI - Surgical lessons learned from the Shigella dysenteriae type I epidemic.
AB - An epidemic of Shigella dysenteriae type I is spreading through Africa. It is a
particularly infectious and virulent form of dysentery which can cause clinical
confusion with other endemic diseases and may present to the surgeon as a result
of its complications. A total of 140 children with Shigella dysenteriae type I
presented to the paediatricians at King Edward VIII Hospital in 1995; 35 were
referred to the surgeons because of abdominal tenderness, distension, peritonitis
or perforation. Ten children underwent laparotomy--four for peritonitis and six
for perforation. Of the four children with peritonitis, three had transmural
colitis. Therefore laparotomy was only performed for objective evidence of
perforation. Of the subsequent non-operated group with the clinical features of
peritonitis, none developed further surgical problems in the acute phase and none
died. It is suggested that surgery in the acute phase should be avoided unless
there is evidence of perforation.
PMID- 9654876
TI - Serum albumin: a prognostic indicator in patients with colorectal cancer.
AB - Various prognostic factors for survival have been identified in patients with
colorectal cancer. However, although it has been suggested that the pre-treatment
serum albumin concentration is a prognostic indicator in certain malignant
diseases (melanoma, prostate cancer, leukaemia), its value in patients with
colorectal cancer remains unclear. This study investigated the prognostic value
of serum albumin in this patient group. A total of 431 patients presenting to the
Professorial Surgical Unit between 1972 and 1985 were analysed in this study.
Using the Cox proportional hazard model, age, tumour stage (Dukes' stage) and
tumour differentiation were shown to be independent prognostic factors for
survival in patients with localized colorectal cancer. In addition, the pre
treatment serum albumin concentration was found to be an independent prognostic
indicator. This is the first such documentation for patients with 'curable'
colorectal cancer.
PMID- 9654877
TI - Total gastrectomy for gastric cancer: the rationale for J-pouch reservoir.
AB - This prospective study examines the results of total gastrectomy in 56
consecutive patients (38 males and 18 females) and compares Hunt-Limo-Basto J
pouch reconstruction (23 patients) with simple oesophago-jejunostomy (33
patients). There was no difference in morbidity and mortality between the two
groups, which are fairly well-matched proportionately in age, concomitant disease
and stage of disease. There was, however, a male predominance in the non-pouch
group. Anastomotic leak occurred in only one patient with gastric reconstruction
while one duodenal stump leak developed in the non-pouch patient. Construction of
the stapled J-pouch extended the operation by a mean time of 14 min. The only
advantage of the J-pouch is that it facilitates introduction of a larger diameter
stapler for oesophago-jejunostomy. The nutritional benefit remains uncertain.
PMID- 9654878
TI - Wounds of Wewak, Papua New Guinea.
AB - Wounds encountered in the outpatients (A&E) department of Wewak General Hospital
in Papua New Guinea were observed during a 3-week visit. A series of 14
accidental wounds and nine resulting from attack were analysed. It was found that
there were predisposing social factors of alcohol, conjugal disputes and
'payback' retribution attacks. Physical factors affecting the outcome were
nutritional status and a high rate of wound infection. Broken bottles and cans
caused some of the injuries. Many aspects of the problem were thus the same as in
the UK, but the resources available to help the patients were much more limited.
PMID- 9654879
TI - Pre-admission clinic in an orthopaedic department: evaluation over a 6-month
period.
AB - A pre-admission clinic for patients undergoing elective orthopaedic surgery has
been used at the Royal Surrey County Hospital, Guildford, for the past 3 years.
This report audits the activities of the clinic over a period of 6 months. Data
regarding the patients who were invited to the pre-admission clinic during the
study period were analysed. In all, 232 patients were asked to attend the clinic
and a total of 221 (95.2%) attended. Of these patients, 10 had their operations
cancelled and three had their operations postponed in the clinic due to various
medical and social reasons. Another 28 operations were cancelled or postponed at
a later stage. All of the postponed procedures were eventually performed within 3
months. Of the 232 patients, 180 (77.5%) underwent their operation on the
arranged day without any complications. The pre-admission clinic in our
orthopaedic department helps us to prevent a significant number of operation
cancellations on the day of admission. It also facilitates an extensive pre
operative assessment of the patients and reduces the ward-based workload of the
junior medical staff. More extensive use of the pre-admission clinic is
recommended.
PMID- 9654880
TI - Prospective study on factors delaying surgery in ruptured abdominal aortic
aneurysms.
AB - Delays between rupture, eventual diagnosis and the repair of abdominal aortic
aneurysms (AAAs) can significantly affect outcome, but the reasons for such
delays in management are not always clear. A prospective study was, therefore,
performed on 30 patients with ruptured AAAs. Twenty-three male and seven female
patients, mean age 71.3 years, were studied. The general practitioner had made
the correct diagnosis in only 38% of cases and the most common misdiagnosis was
renal colic (24%). Non-vascular hospital doctors made the correct diagnosis in
55% of cases, but patients with back pain were the most frequently misdiagnosed
by both types of doctor. The performance of an ultrasound scan significantly
delayed referral to the vascular unit from a median of 0.75 to 2.50 hours and was
of little benefit in aiding the diagnosis. In conclusion, the most striking delay
factors in the management of ruptured AAAs are the high incidence of misdiagnosis
and the lack of benefit of ultrasound scanning.
PMID- 9654881
TI - Trigeminal neuralgia, trophic ulceration and the plastic surgeon.
AB - An 80-year-old woman presented with ulceration to the right alar margin about 20
years after first undergoing treatment for trigeminal neuralgia. This was
reconstructed with a sensory innervated left nasal flap. Two years later she
required an innervated left forehead flap to correct a secondary ectropion of the
right lower eyelid, and the following year required further surgery to repair a
defect on her chin. Cosmesis remains satisfactory with no further ulceration 2
years after the last operation.
PMID- 9654882
TI - What do plastic surgeons do?
AB - The image of plastic surgery as portrayed by the media is of concern to all
plastic surgeons. In order to assess knowledge about the specialty, a
questionnaire was devised and given to five groups of participants: general
practitioners, medical students, nurses, plastic surgical out-patient attendees,
and the general public. The results revealed that general practitioners, nurses
and medical students in the Cambridge area are, on the whole, knowledgeable about
the role of plastic surgery. However, the general public are not so well educated
and 23.7% of them could not think of five conditions treated by plastic surgeons,
and felt that burns and cosmetic problems were the commonest conditions dealt
with. Improved liaison with general practitioners, other specialties and more
teaching of undergraduates, coupled with more effective promotion of the skills
on offer might permit better use to be made of the specialty.
PMID- 9654883
TI - A comparison of conservative, radical and laser palatal surgery for snoring.
AB - Reports of snoring are common among serviceman in the armed forces. Continuous
positive airway pressure (CPAP) is usually an inappropriate modality for
servicemen, but surgery, although requested, is very painful. In an attempt to
reduce the pain, a laser has been used to perform uvulopalatopharyngoplasty and
the more conservative uvulopalatoplasty has also been performed. Before
proceeding to a randomized trial, this retrospective study was performed by
questionnaire comparing these operations with conventional
uvulopalatopharyngoplasty. Fifty-two completed replies from 63 patients were
analysed. The results have to be interpreted with caution because of the small
sample sizes; however, the results in the three groups were similar. The study
suggests that each operation works well, but that any reduction in pain from
performing uvulopalatoplasty or by using a laser is likely to be small. The study
also found that the incidence of dryness as a complication is much higher than
previously estimated.
PMID- 9654884
TI - An unnecessary femoral amputation?
AB - Non-traumatic gas gangrene is extremely rare. It is commonly associated with
perforation of an occult gastro-intestinal cancer. The patient's course is
usually fulminant. We report a case of subcutaneous emphysema and myonecrosis of
the lower extremity due to a perforated carcinoma of the large bowel. The
diagnosis of colonic cancer was suspected but treatment was regrettably delayed
leading to the perforation and subsequent lower extremity gas gangrene. The
patient survived following a femoral amputation.
PMID- 9654885
TI - Candidal urinary tract infection as a cause of pneumaturia.
AB - Colonization of the urinary tract by Candida species occurs particularly in
diabetic or immunocompromised patients. We report the cases of two patients
presenting with pneumaturia and urinary tract infection who were initially
thought to have colovesical fistulae. In both patients a diagnosis of
emphysematous pyelonephritis or cystitis due to candidal infection was
subsequently made. These cases serve as a reminder of this rare presentation of a
not uncommon urinary tract infection.
PMID- 9654886
TI - Splenosis of the mesoappendix: case report and review of the literature.
AB - The development of splenosis is a known consequence of splenic rupture. A case is
presented of acute appendicitis in a patient with a past history of abdominal
trauma who required laparotomy for unknown reasons. During appendicectomy a mass
was found in the mesoappendix which proved to be evidence of splenosis.
PMID- 9654887
TI - Small bowel obstruction caused by a dislodged biliary stent.
AB - Biliary stents are commonly used in the management of obstructive jaundice.
Complications at the time of insertion are not uncommon, but late complications
due to dislodged stents have not been previously reported.
PMID- 9654888
TI - Myxoglobulosis, a rare variant of appendiceal mucocele, occurring secondary to an
occlusive membrane.
AB - A 77-year-old man presented with altered bowel habit and episodic right lower
abdominal discomfort. A barium enema showed a large smooth filling defect in the
caecum and at operation his appendix was seen to be hugely distended.
Pathological examination showed myxoglobulosis, a rare variant of mucocele of the
appendix. The appendiceal orifice was completely occluded by an imperforate
membrane with no communication between the appendix and caecum. This is the first
published report in the English language of appendiceal myxoglobulosis in
association with such an occlusive membrane.
PMID- 9654889
TI - Extracranial giant cell arteritis.
AB - Although giant cell arteritis (GCA) of the extracranial arteries is said to be
relatively frequent, clinical manifestations are rarely recognized. We describe a
case presenting with intestinal perforation who subsequently died with active GCA
of the coronary, mesenteric and temporal vessels.
PMID- 9654890
TI - A mathematical model of growth of population of fish in the larval stage: density
dependence effects.
AB - A mathematical model for the growth of a population of fish in the larval stage
is proposed. The emphasis is put on the first part of the larval stage, when the
larvae are still passive. It is assumed that during this stage, the larvae move
with the phytoplankton on which they feed and share their food equally, leading
to ratio-dependence. The other stages of the life cycle are modeled using simple
demographic mechanisms. A distinguishing feature of the model is that the exit
from the early larval stage as well as from the active one is determined in terms
of a threshold to be reached by the larvae. Simplifying the model further on, the
whole dynamics is reduced to a two dimensional system of state-dependent delay
equations. The model is put in perspective with some of the main hypotheses
proposed in the literature as an explanation to the massive destruction which
occurs between the egg stage and the adult stage.
PMID- 9654892
TI - Food chain dynamics in the chemostat.
AB - The asymptotic behavior of a tri-trophic food chain model in the chemostat is
studied. The Monod-Herbert growth model is used for all trophic levels. The
analysis is carried out numerically, by finding both local and global
bifurcations of equilibria and of limit cycles with respect to two chemostat
control parameters: the dilution rate of the chemostat and the concentration of
input substrate. It is shown that the bifurcation structure of the food chain
model has much in common with the bifurcation structure of a one-dimensional map
with two turning points. This map is used to explain how attractors are created
and destroyed under variation of the bifurcation parameters. It is shown that low
as well as high concentration of input substrate can lead to extinction of the
highest trophic level.
PMID- 9654891
TI - A modified model for projecting age-structured populations in random
environments.
AB - A discrete-time age-structured population model with vital rates linked to a
stochastic environmental process was developed as a generalization of an existing
model by making the explicit link between variability in the vital rates and
variability in the environment more flexible. This modified model uses
biologically relevant probability distributions for the vital rates, and allows
for temporal autocorrelation and an arbitrary covariance structure between vital
rates. Through simulations, the properties of the projected population in the
short-term were investigated and compared to analytical approximations. The
distribution of the total population size did not quickly approach lognormality
under all conditions. Furthermore, the sensitivity of the vital rates to the
environmental process had a strong effect on the variance and distribution of the
projected population size. These results suggest that short-term projections need
to be carried out through simulation methods, as the analytical approximations
technically apply only to the long-run asymptotic behavior. Techniques for
parameter estimation were considered; recommendations depend on the form of the
data available. The approach described allows the empirical calculation of the
probability distribution for predicted population size, a quantity relevant to
the use of formal decision analysis in natural resource management.
PMID- 9654893
TI - A model of multiple tumorigenesis allowing for cell death: quantitative insight
into biological effects of urethane.
AB - This paper considers the utility of a stochastic model of carcinogenesis proposed
by Yakovlev and Polig [Math. Biosci. 132 (1996) 1-33] in the analysis of
experimental data on multiple tumors induced by chemical carcinogens. The model
provides a good description of published data on multiple tumors developing in
the lungs of mice in response to different schedules of urethane. The
distribution of pulmonary tumor counts appears to be negative binomial for each
period of time after exposure to urethane. Our results suggest that the rate of
administration of urethane has little effect both on the mean number of initiated
cells per unit dose and on the rate of formation of lesions responsible for cell
death. As our estimates show, more than 80% of initiated cells die in the course
of tumor promotion. The model is robust to variations in the rate of urethane
excretion given a fixed total dose of the carcinogen. Some prospects for further
development of the model to allow for expansion of promoted cell clones are
discussed.
PMID- 9654894
TI - Statistical certification of eradication of poliomyelitis in the Americas.
AB - The last confirmed case of paralytic poliomyelitis due to indigenous wild
poliovirus in the Americas occurred in Peru in 1991. In 1994 the International
Commission on Polio Eradication of the Pan American Health Organization (PAHO)
deemed eradication of polio from the area to have occurred, based on its
strategic efforts and the observed results. A mathematical model is presented
here which relates the time elapsed since that last detected case of paralytic
poliomyelitis caused by wild poliovirus to the probability that the transmission
of indigenous wild poliovirus has been stopped. The appropriateness of applying
the model to various geographical areas of the Americas is investigated using
data about the occurrence of confirmed cases of polio since 1984, the time of the
eradication initiative adopted by PAHO. The model suggests that if four year have
elapsed since the last reported confirmed case of polio caused by wild
poliovirus, and no other confirmed cases have been identified, the probability of
undetected indigenous wild poliovirus transmission is less than 5%. An important
assumption is that the eradication strategy implemented by PAHO has yielded
steady improvements. A consequence of this approach is that the annual
probabilities of persistence given by the model are conservative, in the sense of
being higher than the true, but unknown a priori probabilities, and more so with
each passing year. It is thus seen that the model results are compatible with the
conclusion reached by PAHO in 1994. The model takes into account the intensity of
surveillance of each country in the region, measured by the corresponding rates
of acute flaccid paralysis (AFP). Because importations of wild poliovirus may
occur from other regions of the world, surveillance efforts are being maintained
in the Americas until global eradication has been achieved.
PMID- 9654895
TI - A plague upon your cattle.
PMID- 9654896
TI - Ischemic stroke syndromes: classification, pathophysiology and clinical features.
PMID- 9654897
TI - The role of correctional facilities in public health: the example of sexually
transmitted diseases.
PMID- 9654898
TI - The economic cost of strict syringe control.
PMID- 9654899
TI - The need for compassionate care: HIV infection among incarcerated women.
PMID- 9654900
TI - The creative clinician: images in medicine.
PMID- 9654901
TI - Health care quality improvements in Rhode Island diabetes mellitus.
PMID- 9654902
TI - AIDS morbidity and mortality in Rhode Island.
PMID- 9654903
TI - Cancer control report card: Rhode Island, 1998.
PMID- 9654904
TI - Queen Elizabeth I's bout with smallpox.
PMID- 9654905
TI - [Dr. Alport and London].
PMID- 9654906
TI - [Effects of doxazosin and hydralazine on insulin sensitivity and sympathetic
function in spontaneously hypertensive rat (SHR)].
AB - Since insulin resistance and/or hyperinsulinemia may contribute to structural
changes of the vascular wall, the influence of antihypertensive agents on insulin
sensitivity could interfere with the long term outcome of blood pressure
reduction. Although it is postulated that increased peripheral circulation due to
vasodilating agents improves insulin sensitivity, reflex sympathetic activation
elicited by blood pressure reduction may influence insulin sensitivity. Thus we
investigated the different effects of an alpha blocker (doxazosin) as well as a
direct vasodilation (hydralazine) on insulin sensitivity and on sympathetic
function in spontaneously hypertensive rats (SHR). Doxazosin and hydralazine
decreased mean arterial pressure to a similar extent. Doxazosin, but not
hydralazine decreased steady state blood glucose. Plasma norepinephrine increased
in doxazosin and hydralazine treated groups as compared to the control group.
Thus, despite their similar effects on blood pressure and plasma norepinephrine,
alpha-1 blocker improved insulin sensitivity while the direct vasodilator failed
to do so, and this difference is probably related to blockade of the alpha-1
receptor rather than to peripheral vasodilation.
PMID- 9654907
TI - [Effects of glucose and TGF-beta 1 on the proliferation of cultured human
peritoneal mesothelial cells].
AB - The exfoliation and decrease is peritoneal mesothelial cells and the presence of
interstitium hyperplasia are often observed in peritoneal membrane dysfunction
caused by long-term peritoneal dialysis. The suppression of peritoneal
mesothelial cell proliferation may be the cause of these phenomena. The objective
of this study is to clarify the mechanism by which highly concentrated glucose of
peritoneal dialysis fluid inhibits mesothelial cell proliferation. We examined
the effect of highly concentrated glucose in the medium on human peritoneal
mesothelial cell proliferation and TGF-beta 1 mRNA expression. The effect of
Ham's F12 media containing various levels of glucose concentration was compared
with that of normal medium. We investigated human peritoneal mesothelial cell
proliferation by [3H] thymidine incorporation assay and TGF-beta 1 mRNA
expression on human mesothelial cells by the RT-PCR method. The suppression
effect of glucose and TGF-beta 1 on human peritoneal mesothelial cell
proliferation was dose-dependent (glucose; 0-5%, TGF-beta 1; 0-1000 pg/ml). TGF
beta 1 mRNA of cells in 4% glucose medium was greater than that in the control
medium. The glucose-induced suppression of human peritoneal mesothelial cell
proliferation was relieved by LAP and TGF-beta neutralizing antibody. In
conclusion, TGF-beta 1 may play a critical role in inhibiting mesothelial cell
proliferation in media with highly concentrated glucose.
PMID- 9654908
TI - [The impact of low calcium dialysate (1.25 mmol/l; LCD) on bone metabolism in
CAPD patients].
AB - The aim of this study was to evaluate the influence of LCD on bone metabolism,
and assess the indication of LCD. Fourteen patients on CAPD (m = 8, f = 6) were
converted to LCD following over 1 year on standard calcium dialysate (1.75
mmol/l; SCD) treatment, and followed for 1 year. The biochemical measurements
included plasma levels of Ca, P, ALP, and i-PTH. The bone mineral density (BMD)
was evaluated using dual energy x-ray absorptiometry. Ca-carbonate and calcitriol
were administered to maintain plasma Ca levels within the normal range. The
patients were divided into three groups on the basis of the i-PTH levels just
before the conversion to LCD. Group 1; n = 5, i-PTH < 65. Group 2; n = 5, 65 < or
= i-PTH < 200. Group 3; n = 4, 200 < or = i-PTH (pg/ml). Mean BMD Z scores
decreased significantly in group 3. Mean serum i-PTH significantly increased in
all groups. These results suggest that LCD is effective for treating adynamic
bone disease, which is seen in high frequency in patients undergoing peritoneal
dialysis. However, these results also pointed to the disadvantage of worsening
the secondary hyperparathyroidism. In conclusion, LCD should be used carefully in
patients whose i-PTH levels are high, because of the possibility of bone mineral
loss.
PMID- 9654909
TI - [The influence of correction of acidosis on plasma level of branched-chain amino
acids in chronic hemodialysis patients].
AB - Seven patients undergoing chronic hemodialysis three times a week and whose
plasma bicarbonate concentration on predialysis was consistently under 18 mmol/l
due to bicarbonate dialysis (BCD), were treated with BCD for 2 weeks, then
switched to acetate-free biofiltration (AFB) for 8 weeks. In both periods, the
same high flux dialyzer (AN69HF) was used. The treatment time, dialysate flow
rate and blood flow rate were kept constant in each patient during both periods.
Plasma bicarbonate concentration (HCO3-), serum urea nitrogen (SUN), serum
creatinine (Cr) and plasma amino acids concentrations (AA) were measured before
dialysis and KT/V was calculated on the 2nd days of the last week in both
periods. HCO3- on AFB was significantly higher than that on BCD (16.4 +/- 0.9 vs
19.9 +/- 1.8 mmol/l; p < 0.05). SUN on AFB was significantly lower than that on
BCD even though the dialysis schedule and dietary content were not changed (84.7
+/- 3.7 vs 76.6 +/- 3.8 mg/dl; p < 0.05). TP, Cr and KT/V were not significantly
different. Plasma total amino acid concentration (TAA) and plasma essential amino
acid concentration (EAA) were not significantly different in both periods. In
contrast, plasma branched-chain amino acid concentrations (BCAA) on AFB were
significantly higher than that on BCD (313.5 +/- 44.3 vs 390.3 +/- 50.7 mumol/l;
p < 0.05). Plasma BCAA concentrations, valine (VAL), leucine (LEU) and isoleucine
(ILE), were significantly higher on AFB than that on BCD, respectively (p <
0.05). These findings suggest that optimal correction of the metabolic acidosis
in chronic hemodialysis patients by AFB leads to a significant increase in plasma
BCAA concentration.
PMID- 9654910
TI - [An electron microscopic study of circumferential mesangial interposition in
various renal diseases].
AB - It has been reported that circumferential mesangial interposition (CMI) is an
important morphological feature suggesting the progression of glomerulosclerosis
in glomerular disease. The relation between CMI and its associated lesions was
investigated in various renal diseases by electron microscopy. In 276 patients,
of whom the glomeruli were observed by electron microscopy, CMI was observed non
specifically in 48 patients with various glomerular diseases (IgA nephropathy,
11; non-IgA glomerulonephritis, 1; membranoproliferative glomerulonephritis, 8;
membranous nephropathy, 5; lupus glomerulonephritis, 12; toxemia of pregnancy, 2;
diabetic nephropathy, 7; mitomycin nephropathy, 1; and Seckel's dwarfism
patients, 1). The glomeruli with CMI showed a marked increase in mesangial
matrix, as well as various grades of mesangial cell proliferation. Mesangiolysis
associated with subendothelial widening was observed in a lesion of CMI in most
cases. This phenomenon appears to be an initial alteration that conducts
proliferated cells to the peripheral portion of a capillary loop. Localized
severe thinning of the glomerular basement membrane was frequently combined with
CMI, particularly in IgA nephropathy patients. Endothelial cells were
occasionally interposed into the widened subendothelial space. Subendothelial
deposits were noticed in the CMI lesion, particularly in MPGN patients. In
conclusion, in the process of glomerulosclerosis progression in various
glomerular diseases, lytic and edematous changes initially occur in the mesangio
subendothelial system (mesangiolysis and subendothelial widening), then
proliferating mesangial cells extend into the widened space (between GBM and
endothelial cells), and reach the peripheral portion of a capillary loop.
PMID- 9654911
TI - [Participation of apoptosis in renal amyloidosis].
AB - Renal amyloidosis shows symptoms of renal dysfunction due to the deposition of
amyloid protein in the kidney. Recently, it was reported that apoptosis plays an
important role in the pathogenesis of type-2 diabetes mellitus and Alzheimer's
disease of which amyloid deposition is seen in the tissue. We investigated
whether or not apoptosis and related factors are observed in renal amyloidosis.
In situ nick end labeling (TUNEL) was performed in seven autopsied renal tissues
with primary and secondary amyloidosis and 10 autopsied renal tissues without
renal disease as the control. The number of TUNEL-positive cells was
significantly increased in both the glomeruli and tubulus of the kidney with
amyloidosis than in the control. Electron microscopic analysis was performed on
one biopsied renal tissue with amyloidosis and six biopsied renal tissues with
minor abnormalities as the control. Typical apoptotic cells were observed only in
the former. Bax product, an inducer of apoptosis, and Bcl-2 protein, an inhibitor
of apoptosis, were examined immunohistochemically in the seven autopsied renal
tissues with amyloidosis and 10 autopsied control tissues. Bax was overexpressed
in the tubulus and glomeruli of subjects with renal amyloidosis, compared to the
normal controls. However, Bcl-2 protein was not detected in the glomeruli in any
of the subjects examined. These results indicate that apoptotic cells are
increased in number in renal amyloidosis and Bax overexpression may play an
important role in this increase.
PMID- 9654912
TI - [A case of systemic AA amyloidosis complicating Crohn's disease].
AB - Although systemic AA amyloidosis complicating Crohn's disease has been found in
0.5 to 6% in America and Europe, it is relatively rare in Japan. We report a case
of systemic AA amyloidosis complicating Crohn's disease. In 1979, a 26-year-old
Japanese man presented with diarrhea, melena and perianal abscesses, and was
diagnosed as having Crohn's disease. He was treated with oral prednisolone,
salazosulfapyridine and diet therapy. However, the gastrointestinal symptoms
recurred and he was hospitalized several times. In 1991, his thyroid gland was
found to be swollen, but with normal thyroid function, and his thyroid gland
became larger subsequently. In October 1995, he showed renal dysfunction (blood
urea nitrogen 33.2 mg/dl; serum creatinine 1.5 mg/dl) with proteinuria. His renal
function had been deteriorating rapidly. On September 13, 1996, he was admitted
to the Tsukuba University Hospital. At the time of admission, his renal function
showed a blood urea nitrogen of 129.5 mg/dl with a creatinine of 5.4 mg/dl. The
urine contained 0.8 g of protein per 24 hours. He presented with diarrhea for
several days before admission and was treated with central venous
hyperalimentation. Despite supportive care, he developed end-stage renal failure,
then hemodialysis was initiated on October 7. His condition was complicated by a
complete auriculoventricular block on October 18. He died of hemoperitoneum on
October 25. On postmortem examination, extensive amyloid deposits were found in
multiple organs including kidneys, intestine, heart, thyroid gland, lungs, liver,
spleen, pancreas, gall bladder, adrenal glands, testis, prostate, bone marrow and
parathyroid glands. Analysis of amyloid protein in the autopsy specimens showed
type AA.
PMID- 9654913
TI - [A case of hepatitis C virus associated membranous glomerulonephritis ameliorated
by corticosteroid therapy].
AB - We report a 50-year-old male patient with hepatitis C virus (HCV)-associated
membranous glomerulonephritis (MN), for which he had been treated with
corticosteroid therapy for one and a half years. This patient received blood
infusion at 38 years of age. He visited our hospital because of liver dysfunction
at 42 years. One year later, proteinuria and microhematuria were pointed out (43
years). Renal biopsy revealed MN with focal fibrocellular crescents. HBsAg,
cryoglobulin, rheumatoid factor were all negative. Prednisolone was administered
at the dose of 30 mg/day for 4 weeks and tapered subsequently. The steroid
treatment was effective (urinary protein excretion: 4.2-->0.3 g/day, serum
albumin: 2.4-->4.0 g/dl, 3 months later), and transaminase slightly elevated (GPT
50-->60-80 IU/l). One and a half years later he proved to be positive for HCV
antibody, and corticosteroid administration was terminated. Subsequently
proteinuria increased, and reached 3.0 g/day 6 years later. However, serological
markers and ultrasonographic study for chronic hepatitis revealed mild changes of
the liver. These findings suggest that corticosteroid therapy is not
contraindicated against HCV-associated MN, and may possibly be used as the
treatment for this condition.
PMID- 9654914
TI - [A case of scleroderma renal crisis with massive pericardial effusion and
positivity on antiphospholipid antibody test].
AB - A 47-year-old woman was admitted to our hospital for evaluation of general
fatigue and dyspnea. She had been diagnosed with progressive systemic sclerosis
(PSS) when she was 39 years of age, on the basis of Raynaud's phenomenon,
proximal sclerosis, and pigmentation of the skin. On admission, her blood
pressure was 206/128 mmHg. Funduscopy revealed grade III (Keith & Wagener)
hypertensive retinopathy. Laboratory data showed positivity for anti-nuclear
antibody and anticardiolipin beta 2 glycoprotein I antibody, and the plasma level
of renin activity (PRA) was abnormally high. Chest X-ray and UCG revealed massive
pericardial effusion. On the second hospital day, she was operated on for
pericardiodiaphragmatic fenestration. The volume of pericardial effusion amounted
to more than 2000 ml. Post operative malignant hypertension persisted. Laboratory
data showed thrombocytopenia, hemolytic anemia, and acute renal failure. We
diagnosed scleroderma renal crisis (SRC) associated with antiphospholipid
syndrome. Following the initiation of angiotensin converting enzyme inhibitor
(ACE-I) combined with calcium antagonist and alpha-one blocker, her blood
pressure and PRA decreased. She also had been treated with aspirin 81 mg daily.
These therapies were effective in recovering the platelet count and stopped the
progression of anemia and renal failure. Although either the finding of large
pericardial effusion or SRC is associated with poor prognosis in PSS, this case
has had a good clinical course. In this case, the findings suggested that anti
phospholipid antibody may have contributed to the pericarditis and SRC.
PMID- 9654915
TI - [Membranoproliferative glomerulonephritis-like lesion with fibrillary deposition
associated with multicentric Castleman's disease].
AB - We report a case of a 65-year-old man presenting with multicentric Castleman's
disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion
with fibrillary deposits. The lesion was characterized by highly organized
ultrastructual deposits that were negative for Congo-red stain and for
immunoglobulin, light chain and C3. Thus, this renal lesion was considered
histologically to be fibrillary glomerulonephritis presenting by light microscopy
as mesangiocapillary glomerulonephritis. To our knowledge, among the limited
number of cases of renal lesion associated with MCD ever reported, this is the
first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6
(IL-6), known as an indicator of MCD activity and as an autocrine growth factor
for mesangial cells, was chronologically measured. Augmentation of urinary IL-6
simultaneously with that of extra renal symptoms of MCD and associated renal
disease may indicate an underlying role of this cytokine in the present case.
Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is
derived from extrarenal lymphonodi, and not to an in situ product of the
glomeruli. However, it may have been related to glomerular injury.
PMID- 9654916
TI - [A case of Bartter's syndrome with chronic renal failure due to chronic
interstitial nephritis].
AB - We report a case of 45-year-old women with Bartter's syndrome and concomitant
renal dysfunction. In 1986, the patient demonstrated muscle weakness and serum
potassium levels as low as 1.1 mEq/l. She was suspected of having Bartter's
syndrome because of hypokalemia, metabolic alkalosis, hyperreninemia,
hyperaldosteronism and normotension. Pretibial edema developed in 1989 for which
she received 40 to 100 mg/week of furosemide intermittently for the next 5 years.
Her serum potassium level ranged from 1.5 to 3.9 mEq/l. In 1991, her serum
creatinine level rose to 2.1 mg/dl, then continued to increase gradually. She was
admitted to our hospital in 1994 for evaluation of the renal dysfunction.
Decreased creatinine clearance (44 ml/min) and a defect in urinary concentrating
capacity (Fishberg's test, 370 mOsm/kg.H2O) were detected. Renal biopsy revealed
juxtaglomerular cell hyperplasia. These findings resulted in the diagnosis of
Bartter's syndrome. The renal biopsy also showed diffuse interstitial fibrosis
and marked tubular atrophy. We postulate in this case that long-term hypokalemia
due to Bartter's syndrome and the administration of furosemide led to chronic
interstitial nephritis and renal dysfunction.
PMID- 9654917
TI - Endoventricular patch plasties with septal exclusion for repair of ischemic left
ventricle: technique, results and indications from a series of 781 cases.
AB - Most cases of left ventricular aneurysms undergo operation through resection of
the exteriorized dyskinetic area with longitudinal suturing of the opening and
this technique has been considered by cardiologists (Froehlich et al) to bring no
improvement to the morphology and performance of the left ventricle. Some
technical modifications have been adopted, such as the septal plicature (Cooley)
or circular suturing of the opening (Jatene). Since 1984 our team has used an
endoventricular patch, sutured over the contractile area and excluding the
akinetic non-resectable scars, bringing a significant and calculable improvement
to the left ventricular function. This technique of left ventricular
reconstruction (LVR), called endoventricular circular patch plasty (EVCPP) has
been already used on more than 750 patients (May 97). Clinical and echographic
data for each case are completed by right catheterisation with measurement of the
cardiac output, pulmonary arterial pressures (PAP) and programmed ventricular
stimulation (PVS), in order to detect eventual ventricular tachycardia (IVT).
During left heart catheterisation, the morphology of the left ventricle (LV) is
studied on right and left anterior oblique incidences and the LV ejection
fraction (EF) is checked globally (GEF) and especially in its contractile portion
(CEF). After surgery, a hemodynamic study associated with a PVS, is carried out
during the first post-operative month, and again after one year. Results were
clinically satisfactory in more than 90% of cases (8.9% of NYHA III-IV), and in
more than 90% of cases with ventricular arrhythmia with the hemodynamic
persistent EF at one year, superior to the pre-operative CEF. Thus we have to
propose the following indications: Elective: This ventricular reconstruction can
be recommended for ventricular aneurysms or akinesias with angina, arrhythmias or
attacks of cardiac insufficiency, when GEF > 30% and CEF > 40%. The operative
mortality rate varies from 1,5 to 3%, which is better than allowing natural
evolution. Mandatory: In emergency, when safe immediate circulatory assistance or
a cardiac transplant is unavailable, LVR can give hope for survival to more than
80% of patients, whereas natural evolution is without hope. Finally the operative
indication is uncertain in two contrasting circumstances: In asymptomatic
patients when hemodynamic and angiographic examinations after myocardial
infarction show left ventricular dyskinesia. If GEF is below 40% and CEF below
50%, it seems wise to propose LVR in order to prevent unfavourable evolution. In
end-stage ischemic cardiomyopathies, if the EF is below 20%, CEF is below 30%,
cardiac output is below 1.5 l, and the mean pulmonary pressure is above 25, then
a cardiac transplant should be considered. EVCPP with septal exclusion is a safe
technique and easily reproduced when associated with coronary revascularization
as far as practicable, then EVCPP improves the ventricular function. When
associated with sub-total endocardectomy, then EVCPP allows excellent control of
VA.
PMID- 9654918
TI - Malignant melanoma of the chest wall with an unknown primary lesion.
AB - We report herein the case of a 66-year-old man who underwent resection and
reconstruction of the chest wall due to the presence of a malignant melanoma
without a detectable primary lesion. The patient was discharged in good condition
after receiving chemotherapy but eventually died of multiple bone metastases 2
years after surgery. Throughout the postoperative course, there were no specific
symptoms or findings suggesting the presence of a primary lesion. It was
considered likely that the primary tumor was resolved by spontaneous regression
after chest wall metastasis had been established.
PMID- 9654919
TI - "Hexatuple" coronary bypass with in situ arterial grafts.
AB - A fifty-seven year old male patient with severe three-vessel coronary artery
disease underwent successful coronary bypass surgery in six vessels utilizing the
in situ left internal thoracic and right gastroepiploic arteries. Each arterial
conduit was anastomosed sequentially to as many as three coronary vessels
respectively. Surgical results were excellent and the patient continues to do
very well. A postoperative angiogram showed well-working arterial conduits
without any anastomotic problems. Multiple sequential anastomoses of the in situ
arterial conduits, although rather technically demanding, can provide better long
term results in patients requiring multiple coronary revascularization. When
sequential anastomoses of the right gastroepiploic artery are being considered,
the length and caliber of the artery should be evaluated by an angiogram since it
varies in size compared to the internal thoracic artery.
PMID- 9654920
TI - Thoracic and cardiovascular surgery in Japan during 1996: annual report by the
Japanese Association for Thoracic Surgery. Committee of science.
PMID- 9654921
TI - [Removal of the endocardial pacemaker leads--experience with 16 leads in 10
patients].
AB - Recent advances in pacemaker leads have contributed to the improvement of their
stability at the anchored sites. However, we sometimes have difficulty in
removing them. We have experienced the removal of 16 leads in 10 patients (male:
7, female: 3) in the last 5 years. The age of patients ranged from 48 to 87
years, and the average was 60. The reasons for the removal were as follows;
pocket infection in 6 cases, sepsis in 1 case, ischemic skin erosion in 1 case,
retained fractured ventricular lead in 1 case, fracture of Accufix atrial lead in
1 case. The methods of removal consisted of using the removal kit, the snare or
the basket snare transvenously, direct surgical approach or a combination of
them. We used the removal kit alone in 12 electrodes (6 atrial, 6 ventricular),
and removal of 5 atrial and 3 ventricular leads were successfully by this method
only. The removal of 4 leads by kits alone failed, so that 2 ventricular leads
were removed transvenously, one atrial and one ventricular lead were removed
surgically, and 1 ventricular lead was left untreated. Finally, we were able to
remove 15 of 16 leads (93.3%) successfully. This experience indicates that these
interventions should be performed as less invasively as possible, yet we should
give an explanation to the patients as to the options we may employ when we have
failed in the intended procedure.
PMID- 9654922
TI - [Early recovery after valvular heart surgery].
AB - There have been published not a few reports concerning the early recovery from
heart surgery. But most of them were restricted in CABG cases. We report our
efforts and its results about the early recovery from valvular heart surgery. To
make a contribution to the early recovery we have made some efforts since 1995,
including normothermic perfusion, low-dose fentanyl and introduction of terminal
warm blood cardioplegia. As the results, the tracheal intubation period was
shortened from 12.6 +/- 5.3 (hour) to 6.7 +/- 4.1. The number of the cases who
had tracheal extubation in the operative day increased from 27% to 84%. The
postoperative cardiac function was satisfactory and there were no abdominal or
neurologic disturbances among the patients those who were entered into the early
recovery protocol. We obtained satisfied early recovery in safe after valvular
heart surgery.
PMID- 9654923
TI - [Evaluation of the growth of a new pulmonary trunk after the reconstruction of
right ventricular outflow tract without using an external conduit].
AB - To evaluate the growth of a pulmonary trunk reconstructed without an extracardiac
conduit, the hemodynamics and diameter of a new pulmonary trunk were measured in
5 patients from the right ventriculogram and MRI at postoperative follow-up
periods. There were tetralogy of Fallot with pulmonary atresia in two patients,
tetralogy of Fallot with single coronary in one, truncus arteriosus type I in one
and transposition of the great arteries with ventricular septal defect and
pulmonary stenosis in one. The age at operation ranged from 26 days to 4.5 years.
The posterior wall continuity of the right ventricle and pulmonary artery was
established by the direct pulmonary-right ventricular anastomosis in three
patients and by the interposition of the left atrial appendage in two.
Postoperative follow-up periods ranged from 2 years and 6 months to 3 years and
10 months (median: 2 years and 11 months). In four of them, the postoperative
right ventricular to aortic or left ventricular systolic pressure ratios were
less than 0.4 without any significant systolic pressure gradients between
pulmonary artery and right ventricle. In these four patients, the diameters of
the reconstructed pulmonary trunks grew from 10-18 mm to 18-21 mm
postoperatively. These diameters were more than 100% of normal values. In the
remaining patient with tetralogy of Fallot and single coronary artery, the
obstruction of the new pulmonary trunk by a bulged left atrial appendage, which
was used as the posterior wall, was observed on the right ventricular outflow
tract reconstruction without an extracardiac conduit has growth potential in the
future.
PMID- 9654924
TI - [Surgical stabilization of multiple rib fractures successfully achieved with the
use of long metalic plates].
AB - Surgical stabilization of multiple rib fractures in 5 male patients was
successfully achieved with the use of orthopedic A-O metalic plates, which are
called reconstruction plates. In each patient, we prevented deformity of the rib
cage and flail chest which frequently occurs after multiple rib fractures. Three
of these patients received emergency operations because of severe
hemopneumothorax and flail chest due to crushing injuries to the chest. They were
treated by the standard thoracotomy, hemostasis of intrapleural bleeding, and
stabilization of fractured ribs with reconstruction plates, in addition two of
the patients underwent a single lobectomy to control the pulmonary hemorrhage.
Another two patients were treated with mechanical ventilation and closed-tube
thoracotomy following the chest trauma because their thoracic bleeding from
drainage tubes was tolerable. But flail chest and respiratory insufficiency did
not improve, in spite of positive controlled ventilation as a mode of internal
pneumatic stabilization. Then surgical stabilization of the fractured ribs with
these plates was carried out ten to twelve days after the accidents in each case.
All patients tolerated the surgical procedures well and were successfully removed
from the respirator, demonstrating complete stability of the chest wall. The long
metal reconstruction plates with many perforations were very useful for the
external fixation of segmentary fractured ribs as an external brace. This was
because they were long enough to cover the whole length of the fractured ribs and
moderately soft enough to be appropriately bent or twisted by hand at the time of
operation. Moreover a number of holes in it allowed the suture to pass through
the plate and rib, avoiding displacement of the prosthesis. This is the first
report which describes the usefulness of orthopedic reconstruction plates for the
stabilization of multiple rib fractures.
PMID- 9654925
TI - [A case of congenital partial pericardial defect and anomaly of phrenic nerve
with cystic bronchiectasis].
AB - Congenital partial pericardial defect is a rare anomaly that causes no symptoms
and is often noticed by chance at autopsy or thoracotomy. During an operation on
a patient with bronchiectasis, a partial pericardial defect and anomaly of left
phrenic nerve were found incidently. A 58-year-old man complaining hemoptysis was
referred to our hospital for surgical treatment of the left cystic
bronchiectasis. During a thoracotomy, a partial pericardial defect was noticed.
Moreover the left phrenic nerve could not be found within the operative field. We
performed left pneumonectomy without repair of pericardial defect, and the
patient had a satisfactory postoperative course. A relationship was suggested
between congenital pericardial defect and the anomaly of the phrenic nerve.
PMID- 9654926
TI - [Primary liposarcoma of the anterior mediastinum--case report and review of
literature].
AB - A 76-year-old male with anterior mediastinal tumor was admitted to our hospital.
He had undergone mediastinal lipoma surgery 3 years earlier. The tumor was
excised surgically. Microscopic sections of the tumor showed liposarcoma composed
of myxoid tissue. Further examination of prior specimens taken from this patient
proved this case to be a recurrence of liposarcoma. Poorly differentiated tumors,
which pathologically tend to be more cellular with less fat per cell component,
are likely to have high CT numbers. But CT number is not sufficient to
distinguish well-differentiated liposarcoma from benign lipoma.
PMID- 9654927
TI - [A case of surgical treatment for Loffler's endomyocarditis].
AB - We performed surgical treatment in a case of loffler's endocarditis. The patient
was a 32-year-old male whose first symptom was easy fatigability. Blood count
showed eosinophilia (eosinocyte count 6720/mm3). Echocardiography and
vetriculography showed thickened bilateral endocardium and extension disturbance.
We diagnosed this case as loffler's endocarditis and performed surgical treatment
because medical treatment was unsuccessful. Removal of the thrombus the bilateral
ventricles, endocardectomy and mitral valve replacement were performed.
Endocardectomy required close attention because the border between thickened
endocardium and normal myocardium was obscure. The patient survived surgery, but
postoperative echocardiography (15 days) revealed slightly thickened endocardium
of the right ventricle. He died of left heart failure 1 month after surgery. At
that time, eosinocyte count was 110,000/mm3.
PMID- 9654928
TI - [An emergency aortic valve replacement for cardiogenic shock patient with severe
aortic stenosis and regurgitation using percutaneous cardiopulmonary support].
AB - The percutaneous cardiopulmonary support system (PCPS) was used in a 64-year-old
woman with cardiogenic shock due to sustained ventricular fibrillation (Vf)
caused by severe aortic stenosis and regurgitation. The Vf attack was resistant
to cardioversion and adrenaline for lack of left ventricular support by PCPS. She
was transported to the operation theater with PCPS in situ and emergency aortic
valve replacement was performed. Although preoperative cardiac resuscitation time
was long (35 minutes), she was discharged from the hospital on foot without any
neurological complications on 84th postoperative day. Because PCPS does not
decrease left ventricular systolic stress in poorly contracting dilated heart,
early surgical treatment is needed in patients with severely damaged heart.
PMID- 9654929
TI - [Myxoid leiomyosarcoma of the esophagus].
AB - A 34-year-old male patient with epigastralgia was found to have an esophageal
submucosal tumor based on an endoscopic evaluation 6 years previously. Because an
unusual appearance composed of a heterogeneous solid area and a cyst area on the
endoscopic ultrasonogram and the increased size of the tumor on esophagograms
over the past 3 years were suggestive of a malignant character, an operation was
thus indicated. The tumor, which measured 3.5 x 2.5 x 2.0 cm in size, was
enucleated using videoassisted thoracic surgery and was diagnosed to be a very
rare myxoid leiomyosarcoma with a thorough pathologic examination. To our
knowledge, this is only the second case of esophageal myxoid leiomyosarcoma
reported in the literature. We thus consider this case, which demonstrated an
unique appearance on an endoscopic ultrasonogram, to possibly be beneficial to
the overall diagnostic analysis of esophageal submucosal tumors.
PMID- 9654930
TI - [A case report of recurrent self inserted needle in heart].
AB - A 17-year-old female who had, on two occasions, inserted a total of 7 needles
into her heart and chest wall, resulting in autolesion on both occasions, was
examined. On the first occasion, because the needle end was recognizably
protruding from the right ventricle, we successfully removed the needle without
using ECC. No complications arose prior to discharge, after which she regularly
visited the psychiatric department for treatment. Two months after discharge, she
again inserted needles into her chest wall and was admitted to hospital. At that
time, five needles were evident in the chest wall. During preparation for removal
of the needles under local anesthetic, she escaped from the room. When found in a
ward several hours later, six needles were embedded in her chest wall, the sixth,
most recently inserted needle was an injection needle. Due to the depth to which
the needle had been inserted in the heart, neither the point nor end were
visible, and thus the needle had to be removed using ECC and fluoroscopy.
PMID- 9654931
TI - [Acute mediastinitis due to esophageal perforation--a case report].
AB - A 55-year-old female consulted her family physician because of pharyngeal
discomfort after eating a fish. She underwent rigid fiberscopy and was pointed
out a fish bone. Family physician failed to extract the bone and the patient was
referred to our hospital. However, there was no fish bone in the esophagus when
she underwent second rigid fiberscopy. After eight days she complained of dyspnea
and was referred to our hospital again. Chest X ray film showed marked
enlargement of the mediastinum and she was diagnosed as acute mediastinitis. She
underwent mediastinal drainage by thoracotomy. So tiny perforation was found in
cervical esophagus by endoscopy that primary suture was not done. After two
months' follow up with intravenous hyperalimentation, there was still esophageal
perforation. She underwent the second operation of primary closure with
reinforcement using sternocleidomastoid muscle. Two weeks after the second
operation esophagogram still showed a fistula. So she received injections of
alprostadil and factor XIII. One month after the injections esophagogram showed a
diverticulum without leakage.
PMID- 9654932
TI - [Spontaneous splenic rupture after mitral valve replacement for infective
endocarditis].
AB - We report a successful treatment of massive bleeding due to spontaneous splenic
rupture after mitral valve replacement. A 61-year-old man was admitted to our
hospital for intermittent high fever. An echocardiogram demonstrated a large
vegetation on the posterior cusp of the mitral valve and mitral regurgitation of
moderate degree. Staphylococcus epidermidis was cultured from his arterial blood.
He underwent a mitral valve replacement after 3 weeks of antimicrobiological
therapy with penicillin G crystalline and minocycline hydrochloeide. The patient
fell into hemorrhagic shock on postoperative day 11 after complaining dull pain
on his left upper abdomen for 3 days. A computed tomography demonstrated a
splenic rupture and massive hematoma in the retroperitoneum. A splenic arterial
embolization was done before splenectomy. The blood and clot of 2800 g were
sucked from peritoneal and retroperitoneal cavities. There were no mycotic
aneurysms nor abscess but the torn capsule on the swelled and partially necrotic
spleen. The patient discharged uneventfully on postoperative day 43. Infective
endocarditis frequently causes splenic infarction but rarely splenic rupture.
Anticoagulation therapy after mitral valve replacement might have emphasized the
bleeding in the patient.
PMID- 9654933
TI - [A case of rupture of the diaphragm caused by the plication for diaphragm
eventration].
AB - A 71-year-old woman, in whom the herniation of right-sided diaphragm was
diagnosed, was admitted to our hospital on ambulance car complaining of
increasing right-sided chest pain and worsening of dyspnea. She was given
emergency laparotomy. The transverse colon and omentum pushed the liver backward.
The tight adhesion between transverse colon and diaphragm was released by using
thoracotomy additionally. In pleural cavity, there was prolapsing transverse
colon which was not covered with peritonium and was caused by the rupture of
right-sided diaphragm. The necrotic transverse colon was resected about 30 cm
length. We considered that the rupture was caused not by external injury but by
inflammation after plication for diaphragm eventration three years and ten months
before.
PMID- 9654934
TI - [A case of the pulmonary thrombosis caused by unilateral pulmonary artery
occulusion test].
AB - A 71-year-old male, diagnosed as lung cancer, underwent unilateral pulmonary
occulusion test. Through the guidewire, 7.5 Fr thermodilution catheter with
occlusion balloon was introduced to the left pulmonary artery from the right
internal jugular vein. Heparinized physiological saline solution was injected
into the distal site of the occulusion. The occulusion time was 15 minutes.
Pulmonary artery pressure and wedge pressure were within normal range. Soon after
the examination, the pulmonary arteriogram (PAG) showed the defect of the branch
to the lingular segment and the lower lobe. We made a diagnosis of pulmonary
thrombosis. Three days after the administration of urokinase and heparin, both
pulmonary perfusion scintigram and PAG exhibited the reperfusion to these areas.
After the thrombolytic therapy was accomplished, antithrombin III and protein C
in the serum showed within normal range. It was possible that the damage on the
intima due to the thermodilution catheter or the guidewire and the following
blood congestion by the pulmonary artery occulusion caused the thrombosis.
PMID- 9654935
TI - [Mediastinoscopic diagnosis and drainage of pericardial diverticulum--a case
report].
AB - A 38-year-old male was suspected of having an enlarged pretracheal lymph node on
chest CT scan. At mediastinoscopy, a cystic lesion was recognized, and showed
repeated dilatation and contraction synchronously with the cardiac beat.
Pneumopericardium was demonstrated by intraoperative pneumocystography. The
cystic lesion was diagnosed as pericardial diverticulum. The diverticular wall
was partially resected for drainage of the pericardial fluid. Mediastinoscopy as
a less invasive procedure may be useful for the differential diagnosis of
adenopathies, and in case of lesion such as a small pericardial diverticulum may
allow treatment.
PMID- 9654936
TI - [Decortication in chronic thoracic empyemas--a report of three cases].
AB - Three cases of chronic thoracic empyema treated by decortication are reported
with special reference to the indications for surgery. The first patient was a 68
year-old man who had right chronic thoracic empyema with a bronchopleural
fistula. He underwent open thoracostomy, and decortication was performed after 8
months. The second patient was a 74-year-old man who had right chronic empyema
without bronchopleural fistula. Open thoracostomy was also performed and
decortication was done after 2 months. Postoperative pulmonary function was
significantly improved in both patients. The third patient was a 66-year-old man
who had left chronic empyema with a bronchopleural fistula. He underwent open
thoracostomy and left lower lobectomy, and then decortication and the omental
pedicle flap method were performed after 4 months. All three patients are still
doing well currently. It is concluded that decortication significantly improves
pulmonary function in properly selected patients, and that computed tomography is
helpful for assessing the re-expansion ability of the collapsed lung.
PMID- 9654937
TI - [Acute ventricular septal perforation in a patient with autoimmune hemolytic
anemia].
AB - A 71-year-old woman with autoimmune hemolytic anemia underwent an emergency
endocardial patch repair for ventricular septal perforation after acute
myocardial infarction. Use of washed red blood cells was effective in averting
hemolytic crisis throughout perioperative period. In spite of improvement of her
hemodynamics, liver dysfunction which had been present preoperatively
deteriorated after the operation. Finally she died of hepatic failure on the 21st
postoperative day. Deterioration of liver function could not be associated with
autoimmune hemolytic anemia. To date, little information is available concerning
the influence of cardiopulmonary bypass on hemolysis in patients with autoimmune
hemolytic anemia. Therefore, prudent management and use of washed red blood cells
transfusion would prevent hemolytic aggravation even in open heart surgery.
PMID- 9654938
TI - [A case report of aortic valve replacement following ruptured aneurysm of the
sinus of Valsalva with bicuspid valve].
AB - Only three cases of the combination of bicuspid aortic valve and ruptured
aneurysm of the sinus of Valsalva, associated with previously repaired
coarctation of aorta, have been reported. A twenty-year-old man with a sudden
onset of CHF due to ruptured aneurysm of the sinus of Valsalva underwent
intracardiac repair by direct closure of the sinus Valsalva in combination with
patch closure of a subarterial VSD. Although, no AR was detected preoperatively,
massive regurgitation occurred after the repair due to subsequent failure of
aortic valve coaptation in the present of the bicuspid aortic valve, which was
not diagnosed preoperatively. Aortic valve replacement with SJM 25 mm was
successfully performed.
PMID- 9654939
TI - [Two cases of coronary artery aneurysm including one case of the left main
coronary artery aneurysm].
AB - We report two cases of coronary artery aneurysm including one case of the left
main coronary artery aneurysm. The coronary angiogram of one patient, a 68-year
old male, having anterior chest pain on exertion, revealed left anterior
descending coronary artery (segment 6) aneurysm of 7 mm in diameter with 90%
stenosis distal to the aneurysm and 75% stenosis in the right coronary artery
(segment 2). The coronary angiogram of another patient, a 69-year-old female,
having chest pain unrelated to exertion, revealed left main coronary artery
aneurysm of 25 mm in diameter and delayed filling of contrast medium into the
left anterior descending coronary artery. We decided to operate by the reason of
not only significant coronary artery stenosis but risks of myocardial infarction
due to embolization into distal coronary arteries and rupture of the aneurysm. We
performed coronary artery bypass graftings using the great saphenous veins and
closure of the coronary arteries running into and out the aneurysm under
cardiopulmonary bypass. It is recommended that ligation of the coronary arteries
connecting to the aneurysm or resection of the aneurysm followed by coronary
artery bypass grafting is performed before developing myocardial infarction or
rupture of aneurysm.
PMID- 9654940
TI - [A study on chemical and immunochemical properties and chemotaxonomy of
lipopolysaccharides of Vibrionaceae, in particular Vibrio cholerae and V.
parahaemolyticus].
PMID- 9654941
TI - [DNA vaccination--current status and future prospect--a new approach for
controlling infectious diseases].
PMID- 9654942
TI - [The front line of the study on human oral spirochetes].
PMID- 9654943
TI - [Dextranase of Streptococcus mutans].
PMID- 9654944
TI - [Phylogenetic classification of plant pathogenic mycoplasma].
PMID- 9654945
TI - Prevention of occupationally acquired infections among heath-care workers.
PMID- 9654946
TI - The long QT syndrome.
AB - The LQTS is no longer the rare "zebra" whose purpose is to ensure that trainees
recall that deafness and sudden cardiac death may be related (Jervell and Lange
Nielsen syndrome). Over the past 10 to 20 years, the number of cases of inherited
LQTS (Romano-Ward syndrome) has increased dramatically. It is doubtful that this
reflects a true increase in incidence of disease due to a greater rate of
sporadic gene mutations occurring in the heart or because of a rising incidence
of consanguinity. Rather, the "incidence" of LQTS has risen because of the
emerging awareness of and respect for this electrical malady in the heart.
Understanding the principal elements of the LQTS, knowing the types of
presentations, and being able to identify its presence electrocardiographically
will allow the astute physician to expose this silent killer.
PMID- 9654947
TI - Macrolides: clarithromycin and azithromycin.
PMID- 9654948
TI - Urticaria.
PMID- 9654949
TI - Case 1 presentation of bizarre behaviors.
PMID- 9654950
TI - Case 2 presentation of increasing pallor, fever and malaise.
PMID- 9654951
TI - Case 3 presentation of facial bruises.
PMID- 9654952
TI - Amniotic bands.
PMID- 9654953
TI - Yersinia enterocolitica.
PMID- 9654954
TI - [Multidrug-resistant tuberculosis in Romania].
PMID- 9654955
TI - [Disability in pulmonary tuberculosis in the city of Bucharest].
AB - The authors analyse the invalidity (new retreated cases) for pulmonary
tuberculosis, in a period of 9 years (1986-1994), comparing the time before and
after the December 1989 Revolution, by making a screening in 2 districts of
Bucharest which, by number of population and incidence of tuberculosis, are
representative for Bucharest. In the analyzed time, in Romania was noticed a
three times increase of tuberculosis invalidity, especially due to pulmonary
tuberculosis. In the two districts of Bucharest, in the 1991-1994 period compared
to the 1986-1990 period, an increase in tuberculosis invalidity was noticed in
men and women, the most affected age group being the one with the greatest work
involvement (age 41 to 50). A great percentage of cavitary tuberculosis was
registered (89%), with an increase of bilateral cavitary lesions frequency from
28% to 36% in the last 4 years. In the same time, the amount of deaths among the
retreated patients increased, with a reduction of number of patients returning to
work. All the data show a worsening in the last period (1991-1994) of the
tuberculosis endemic and invalidity by this disease, probably due to the social
and economical factors.
PMID- 9654956
TI - [Initial experiments with controlled assisted ventilation by nasal mask in
exacerbated chronic respiratory failure in chronic obstructive
bronchopneumopathies].
AB - The authors are presenting the first cases in Romania in which volumetric
ventilators Monnal D type were used for external ventilatory assistance on nasal
mask of the chronic obstructive pulmonary diseases in exacerbation. The paper
reviews the problems issued during the use of ventilators in 5 chronic patients,
with numerous previous admittances in our clinic, as well as the latest news in
the field of modern therapy of COPD.
PMID- 9654957
TI - [The epidemiological profile and current evolutionary trends in tuberculosis in
adolescents (15-19 years old) in the capital].
AB - In Bucharest, the increasing TB incidence in the age group of 15 to 19 years till
100.11/100000 in 1996 has to become a concerning matter. The study of 585 cases
aged 15 to 19 registered in Bucharest between 1991 and 1995 (more than 2/3 of all
the cases in that period) revealed the important proportion of secondary TB
(67.4%), as well as the frequency of pleural involvement (25.6%). The main
discovering methods remain the examination of symptomatic cases (78.6%) and
epidemiological inquiry (10%). The fact that 85% of the bacteriological confirmed
cases had positive sputum specimens in microscopy confirms the idea of
discovering the patients in advanced stages of disease, as well as
epidemiological signification. Almost 50% of the ill teen-agers belong to
families with low living status. At this age group we found an important degree
of recovery after chemotherapy (82% rate of healing in the first year).
PMID- 9654958
TI - [Therapeutic management in a case of pleural empyema complicated by ARDS].
PMID- 9654960
TI - [The management of bronchial asthma in adults].
PMID- 9654959
TI - [Bilateral multifocal pulmonary leiomyomatosis].
AB - A case of diffuse primary pulmonary leiomyomatosis with a 24-years-old
asymptomatic woman having a pulmonary radiological aspect of miliary
dissemination 3 years after a myomectomy for sub-serous uterine fibroma. The
diagnosis was established after a surgical pulmonary biopsy. The case presented
certain peculiar features: a young woman; the inter-relation between pulmonary
leiomyomatosis and the operated sub-serous uterine fibroma; the aggravating
factor--the pregnancy; a confirmed probably hormonal cause (hyperestrogenemia); a
progressive aggravating evolution.
PMID- 9654961
TI - [Delayed-action theophyllines with "once a day" administration--a new therapeutic
tool in asthma and COPD].
PMID- 9654962
TI - [Education for health--smoking. Testing the knowledge and behavior of some socio
professional groups--students, parents and teachers].
PMID- 9654964
TI - [The current epidemiological aspects of osteoarticular tuberculosis].
PMID- 9654965
TI - [The chronology and diagnostic round of patients operated on for bronchopulmonary
cancer].
AB - 37 patients with certified diagnosis, operated for lung cancer (LC) in The
Central Military Hospital Bucharest, during six months period (October 1st 1996
June 1st 1997). It was a retrospective study on the patients medical files. Sex
distribution, postsurgical staging and histological type were studied. We
calculated the following delays: 1. Between the first medical examination and the
first suspicion (chest X-ray): 6 +/- 3 days; 2. Between the first medical
examination and first hospital admission: 14 +/- 11 days; 3. Between the first
hospital admission and the first admission in surgical units: 43 +/- 23 days; 4.
Between the first admission in surgical units and surgery: 59 +/- 26 days; 5. The
delay until bronchoscopy: 23 +/- 16 days; 6. The delay until the CT examination:
26 +/- 16 days; 7. Between the first medical examination and the surgery: 78 +/-
30 days. These delays were correlated with the specialty profile of the services
which referred the patients: pulmonology, internal medicine, oncology or primary
services. CONCLUSION: 1. Most patients come from pulmonology units (22 out of 37
patients); 2. There are significant delays until bronchoscopy and CT scan, the
availability of these services is still limited; 3. The primary care medical
network is still inefficient in early diagnosis of LC; 4. The overcrowding of
thoracic surgery unit (scheduling for surgical intervention). All of these are
arguments for developing more efficient and faster circuits of LC diagnosis,
especially for high risk patients.
PMID- 9654966
TI - [The evaluation parameters of the long-term treatment efficacy of theophylline in
the child with bronchial asthma].
AB - In the past decade the use of theophylline was less extensive because of its
narrow therapeutically index and due to its side effects. The widening of
possibilities of monitoring the treatment by serum level determination, the
introduction of slow release formula, and the demonstration of antiinflammatory
effects made theophylline to become actual again. Theophylline is indicated for
the chronic treatment of asthma in association with other medication. The authors
study the efficacy and serum level of theophylline in 13 children with asthma who
received slow release theophylline in a dosage of 15.2 mg/body weight/24 hours in
average, administered 3 times a day. The efficacy was estimated by a clinical
score and the serum level was determined by isotopic mass spectrometry with 15N
theophylline as internal standard. After a period of at least 2 months of therapy
it was recorded the amelioration of clinical score (with 5.09 points, that
represents 36.3% of the maximum initial score) and the reducing of circadian
variation of peak expiratory flow from 27% to 15%. The serum level of
theophylline was of 8.25 +/- 4.16 micrograms/ml at 4 hours after administration
and of 5.69 +/- 2.6 micrograms/ml at 8 hours after administration of the last
dose. The individual values less than 5 micrograms/ml was found in 3 of 13
children at 4 hours and in 7 of 13 children at 8 hours after the last dose. There
were no patients with toxic serum levels of theophylline (> 20 micrograms/ml).
The correlation between serum level of theophylline and the dosage was weak both
at 4 hours (r = 0.054) and 8 hours (r = 0.229) after the last dose. At the same
dose there were found high interindividual variations. These findings are
arguments for the usefulness of determination of serum levels of theophylline,
that together with clinical and functional parameters allowed the
individualization of the dosage.
PMID- 9654967
TI - [Pulmonary fibrosis and systemic sclerosis].
PMID- 9654968
TI - [Pulmonary alveolar microlithiasis--a clinical case].
AB - A new case of alveolar microlithiasis is reported, demanding for the diagnosis
besides the radio-clinical investigations, complete respiratory function tests,
also the pathologic proof. Authors recall the diagnostic approach and our present
ignorance of the pathogenesis of this curious entity; no valid therapy is
presently able to check the relentless course toward progressive respiratory
failure.
PMID- 9654969
TI - [The pulmonary syndrome produced by hantaviruses].
PMID- 9654970
TI - [The quality-of-life study in oncology with reference to bronchopulmonary
carcinomas].
PMID- 9654972
TI - [Recommendations for bronchoscopic treatment of tracheobronchial occlusions,
stenoses and mural malignant tumors. German Society of Pneumology "Quality
Assurance in Bronchology" Working Group].
PMID- 9654973
TI - [Endobronchial chondroma--bronchoscopic resection or thoracic surgery
intervention?].
AB - Endobronchial chondromas as a rare form of benign tumors of the bronchial tree
lead not only to diagnostic problems because of the unspecific often latent
pattern of symptoms, but also to therapeutic difficulties because of the
macroscopic findings and the poststenotic changes of the bronchial tree and the
lung parenchyma. In case of a 75-year old female patient the various therapeutic
possibilities are discussed. The therapy must be individual and consider the
extent of simultaneous lung changes and the general criteria of operability in
thoracic surgery.
PMID- 9654974
TI - [Successful therapy of pulmonary aspergillosis in a patient with non-Hodgkin
lymphoma].
AB - ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma
developed severe invasive pulmonary aspergillosis during a state of leucopenia
after chemotherapy. INVESTIGATION: The initial manifestation was an infiltration
in the right upper lobe of the lung, identified by lung scintigraphy as a
peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage
extreme high titre of Aspergillus antigen were seen as a laboratory indication of
an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly
isolated from bronchoalveolar lavage and bronchial secretion. THERAPY AND
CLINICAL COURSE: Treatment was started with amphotericin B plus 5-flucytosine
together with repeatedly bronchoscopic instillation of miconazole followed by
thoracosurgical intervention with resection of the right upper lobe of the lung.
Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred
three months later probably due to persistence of aspergillus fungal elements in
the left lung. The aspergillosis relapse was treated at first with liposomal
amphotericin B. After eighteen days of treatment this was changed to a
combination of 5-flucytosine with oral application of itraconazole, and cure was
achieved.
PMID- 9654975
TI - [Epidemiology, clinical aspects and prognosis of severe progressive community
acquired pneumonia].
AB - BACKGROUND: Community-acquired pneumonia can lead to acute lung failure
(parapneumonic ARDS) if the course is very severe. The clinical picture reflects
a rapidly progressive and potentially fatal respiratory failure. Only occasional
cases in which the clinical courses of community-acquired pneumonia lead to acute
respiratory failure have been reported so far. The investigation was based on the
observation that very severe progressive forms of community-acquired pneumonia
are at present one of the most frequent conditions triggering ARDS. PATIENTS AND
METHODS: A total of 66 patients of both sexes with an average age of 34 +/- 11
years were included in the retrospective investigation. The patients had been
secondarily referred to the center for further treatment. After admission, the
further course of the disease was recorded at five defined times (day of
admission, 2nd day, 7th day, 14th day and day of spontaneous breathing or day of
death). The degree of disturbance of pulmonary function was registered with the
scores of Morel and Murray. Further disorders of organ function were evaluated
with the MOF score according to Goris, the "Definition Multiple disorder of Organ
Function (DeMOF)" and the appraisal of the severity of the systemic inflammatory
reaction with the sepsis score according to Elebute & Stoner. RESULTS: The
duration of preclinical disease was 6 +/- 4 days and the duration of the
pretreatment in the referring hospital was 10 +/- 10 days. A potential primary
causative organism (bacteria n = 18, viruses n = 5, "atypical" pathogens n = 6,
Candida species n = 4) could be isolated in 50% of the patients. A pre-existing
underlying disease was found in 48% of cases. With a total lethality of 31%, this
was affected neither by knowledge of the primary causative organism nor by
previous diseases. The patients who died did so with improved lung function in a
complete clinical picture of multiorgan failure. At the time of admission, 91% of
the patients had severe ARDS (Morel III and IV). An improvement of lung function
could be demonstrated between the day of admission and the second day of
treatment both with the score according to Morel and according to Murray (p <
0.05). For the second day of treatment, a difference could be shown between the
patients who survived and those who died (p < 0.05). Owing to the systemic
inflammatory reactions, a multiorgan functional disorder was found in 89% of the
patients. There were the following findings with regard to the prognostic
predictions from the score used: those who died and those who survived could be
correctly differentiated with the DeMOF score from the 7th day of treatment and
the sepsis from the 7th day of treatment and with the score of Goris from the
14th day of treatment after referral. CONCLUSIONS: The investigation proves that
the most severe progressive forms of community-acquired pneumonia also occur both
in patients who have previously appeared to be healthy and in younger patients.
Despite the use of differentiated treatment measures, these illnesses are subject
to a relatively high lethality. The results underscore the need for causal
treatment of systemic inflammatory reaction, which is the most important problem
in treatment of parapneumonic ARDS.
PMID- 9654976
TI - [Molecular biology methods in epidemiology of tuberculosis].
AB - The spread of tuberculosis often remains undetected and development of disease
may occur years after the primary infection. However, tracing chains of
transmission is an important task for prevention of new cases, especially for
multi-drug-resistant tuberculosis. Today, molecular typing methods have become an
important tool for identification and confirmation of epidemiological links
between tuberculosis patients in an outbreak situation. Differentiation between
strains of Mycobacterium tuberculosis also allows to decide between reactivation
because of treatment failure and superinfection. A growing number of typing
methods have been developed that differ mainly in their reproducibility and the
ability to differentiate between isolates closely related at the molecular level.
Based on further standardisation and automation, molecular typing techniques can
provide pertinent information for tuberculosis control.
PMID- 9654977
TI - [Exogenous surfactant administration and partial fluid ventilation. Physiological
and pathological effects].
PMID- 9654978
TI - [A new method for imaging ventilation-distribution with 3Helium in magnetic
resonance tomography].
AB - BACKGROUND: Conventional 1H-MRI of the lung is restricted by susceptibility
effects and low proton density: Recently, imaging of lung ventilation in MRI has
become feasible using hyperpolarised inert gases with a spin of I = 1/2, such as
3He and 129Xe, as inhalative "contrast agents". New technical developments,
preclinical and clinical application of this method are described. MATERIALS AND
METHODS: With optical laser pumping high polarisation rates can be achieved,
resulting in a high signal-to-noise ratio (S/N). A dedicated application system
allows accurate administration of 3He boli at different time points during
inspiration. Thus, dynamic ventilation imaging becomes possible. Prerequisites
for this method include a dedicated coil as well as a spectroscopy option at the
MRI system. Fast sequences and low flip angles are employed to comply with the
relaxation of hyperpolarise 3He in vivo. RESULTS: Overall homogeneous signal
intensity (SI) represents physiological conditions. Obstructive lung disease is
associated with generalised or localised signal inhomogeneity. Different time
constants of specific lung regions are probably responsible for this kind of
inhomogeneous inspiratory distribution of ventilation. Tumours show a clear
ventilation deficit, correlating with non-ventilated lung areas. CONCLUSION: 3He
MRI is a promising new modality for the evaluation of ventilation distribution
under different pathological conditions. This may include obstructive lung
disease and assessment of ventilation distribution before and after thoracic
surgery. Furthermore, evaluation of patients with acute lung failure and
validation of ventilator settings in anaesthesia may be performed.
PMID- 9654979
TI - [Alveolar hemorrhage syndrome in sarcoidosis].
PMID- 9654980
TI - [Cognitive training and strategy behavior: comparative evaluation of 2 cognitive
training programs].
AB - Combining a non-comparative with a comparative evaluation, two modern programs
for fostering inductive reasoning, namely the German version of the "Cognitive
training for children" by Klauer and Phye (1994; Klauer 1989), and the "DenkMit"
by Sydow and Meincke (1994), are compared to each other and to a control program
which intends to enhance aspects of memory instead of inductive reasoning. The
programs were performed with N = 49 children between six and eight years who had
been postponed from regular school because of various reasons or who had been
selected as especially in need for particular interventions from first classes.
Besides the psychometric test often used for assessing inductive reasoning, i.e.
three subtests of the German form of the Culture Fair Test by Cattell (Weiss a.
Osterland 1980), tasks of concept formation were applied for assessing changes in
strategic behavior of children--a type of task which has been used in connection
with inductive reasoning since many years. Counter to expectations, the children
whose memory was trained, showed changes in performance in the psychometric test
in a similar size as the children whose inductive reasoning was trained. These
effects are interpreted in terms of special attention directed to the children
during the intervention situation. Moreover, it was found that despite the
authors claim to the opposite the DenkMit did not cause any changes in visual
perception. In contrast to the author's intentions, the "Cognitive Training for
Children" did cause some substantive changes in the area of visual perception.
The pattern of results with the concept formation tasks, however, overall
indicates that the reasoning programs caused some changes in strategic behaviors
of the children. Although these changes are not very impressive, they cannot be
attributed to extraneous factors such as special attention.
PMID- 9654981
TI - [Course and prognosis of anorexia nervosa: catamnesis of 41 patients].
AB - The purpose of the following study was a multidimensional assessment of the
course of anorexia nervosa. In our follow-up-study we were able to examine 41 out
of 51 patients meeting DMS-111 R criteria for anorexia nervosa in our department
at a mean follow-up of 5.3 years. At the first evaluation the patients were
characterized by an early age of onset (mean 14.2 years), no or very little
previous psychiatric treatment, and restrictive eating habits (72.5%); the mean
age was 15.2 years. At the time of follow-up, the physical outcome was
unfavourable for 50% of the patients; one patient had died. The psychosocial
outcome was less favourable for 60%. Against the background of a neurotic
structure, social and sexual disturbances were found although the patient's
weight was often normal. Depressive symptoms and a "slimness ideal" were found
among a large number of patients, just as much as the fear of gaining weight-
which prove to be a reliable indicator for the continuation of an eating
disorder. A multidimensional evaluation facilitates an assessment of the
determinants of prognosis. Previous psychiatric treatment and low body weight
were associated with an unfavourable, mention of problems/disturbances in the
family environment with a good somatic outcome. Outpatient treatment indicates a
favourable psychosocial outcome.
PMID- 9654982
TI - [Prognosis of dangerousness in adolescent psychiatry expert assessment].
AB - The clinical assessment and prediction of violent behavior are two of the most
important, but also most difficult tasks for child and adolescent psychiatrists
who work in the forensic psychiatric area. The purpose of this article is to give
an overview about the most prominent aspects of this problem. Therefore the
judicial, methodological and methodical basis of the prediction of dangerous
behavior is discussed as well as different methods that are used to predict
dangerous behavior. It is shown that "dangerousness" is in most cases the result
of an interaction between the individual dispositions of a person and a violence
prone situation. Furthermore it is put emphasis on the fact that many
psychiatrists are not aware of their own cognitive processes that lead them to a
conclusion concerning the dangerousness of a person and also do not use the bulk
of the information that is available to them; so many studies showed that
dangerousness is judged in the first line in the light of former delinquency and
much less in the light of other anamnestic data or the actual behavior. Finally
some proposals are made concerning the improvement of the quality of the clinical
prediction of dangerousness.
PMID- 9654983
TI - [Patient dismissal to promote progress: brief discharge as a possible method in
inpatient psychotherapy of adolescent patients].
AB - In dealing with aggressive juveniles in a setting it often is difficult to
sustain the concept of therapy without risking the end of cooperation. A chance
to save the ability to act on the therapist's side, offers the shorttime
dismissal as a therapeutical measure. It works as a remedy in times of stationary
crises' as well as a juncture with the juvenile's original system that is forced
into the process of therapy closing links between the stationary ongoings and the
dynamics of the familiar system outside.
PMID- 9654984
TI - [The unwanted father: psychodynamic aspects of the relationship after separation
and divorce].
AB - Although the importance of the father for the development of the child is well
known and although an increased presence of the father in the family system is
often demanded, processes of active shutting out the father occur. The
deterioration of relation between father and child is not seen as a result of
pathological male personality, but rather as a result of family or couple system.
The special situation for counsellors of such cases is discussed.
PMID- 9654985
TI - [R.E.A.L. classification of non-Hodgkin lymphoma from the clinico-oncologic
viewpoint].
AB - In 1994 the International Lymphoma Study Group (ILSG) published the "Revised
European-American Classification of Lymphoid Neoplasms" (R.E.A.L.
Classification). Lymphomas were classified according to their presumed normal
counterparts, to the extent possible. Within both T- and B-cell categories
differentiation between lymphomas and/or leukemias of "precursor" or "peripheral"
neoplasms are defined arising from antigen independend or antigen reactive cell
proliferation. Lymphomas undoubtedly characterized by currently available
morphologic, immunologic, and genetic technics represent "real" disease entities.
Provisional categories include lymphomas that have been described in some detail,
but without consensus within the ILSG. Proposed names are based predominantly on
established usage. With respect to similar treatment approaches and difficulties
of the ILSG members in subclassifying large cell lymphomas, centroblastic,
immunoblastic and large cell anaplastic lymphomas of B-cell type were "lumped"
together as large B-cell lymphomas. Within a prospective treatment trial overall
survival was significantly better in centroblastic as compared to B-cell
immunoblastic lymphoma diagnosed by optimal histomorphology according the
criteria of the Kiel Classification. Thus the R.E.A.L. Classification fails to
identify patients who may require other than standard treatment. Future studies
will demonstrate whether subclassifying the proposed "peripheral" T-cell
lymphomas, unspecified into T-zone lymphoma, lymphoepitheloid (Lennert's)
lymphoma and pleomorphic, small, medium, and large cell lymphomas according the
Kiel Classification is of clinicopathologic relevance. On the contrary the
subtypes of chronic lymphocytic leukemia of T-cell type form two distinct
entities within the R.E.A.L. Classification separating T-CLL/prolymphocytic
leukemia from large granular lymphocyte leukemia of T- and NK-cell type. Within
the R.E.A.L. Classification the lymphoplasmacytoid immunocytoma of the Kiel
Classification will be subsumed together with the prognostically significantly
better B-cell chronic lymphocytic leukemia. Opposite to the original intention of
the ILSG two proposals are developed on clinical grouping of entities. Clinical
indolent lymphoid neoplasms usually have "low grade" histologic appearances, with
a predominance of small cells subsuming with the exception of the mantle cell
lymphoma all of the low grade lymphomas of the Kiel classification. Aggressive
lymphomas (intermediate risk) are defined as tumors whose survival if untreated
is measured in months, highly or very aggressive lymphomas and/or leukemias will
kill untreated patients within weeks. Unlike the Kiel Classification proposed
categories subsume lymphomas irrespective of cytomorphology, thus grouping
together potentially curable and uncurable diseases. Undoubtedly the R.E.A.L.
Classification forms at present the best compilation of existing knowledge upon
neoplasms of the immune system, enabling cooperation between clinicians and
scientists all over the world. According to the ILSG this proposal should be
considered a starting point for future periodic reevaluations.
PMID- 9654986
TI - [Radiotherapy alone in early stages of low malignancy non-Hodgkin lymphomas].
AB - About 25% of patients with low grade Non-Hodgkin's Lymphomas (NHL) of the B-cell
type present in an early stage. They are candidates for radiotherapy alone.
Thereby a complete remission can be achieved in the majority of stage I and II
patients with centroblastic-centrocytic (cb-cc), centrocytic (cc) and immunocytic
(ic) NHL--at least in cb-cc also a relapse-free survival of 50-60%.
Standardization of the radiotherapeutic technique is essential to reduce the risk
of recurrence. Retrospective analyses of radiotherapeutic studies from the
literature are limited by the lack of homogenous irradiation techniques. Relapses
occur inside as well outside of radiotherapy ports. It is the aim of current
studies to optimize the radiotherapeutic approach with curative intent.
PMID- 9654987
TI - [Systemic therapy of low malignancy non-Hodgkin lymphomas].
AB - Substantial progress has been achieved in eludicating the molecular mechanisms of
malignant transformation, in establishing therapeutic standards and in evaluating
innovative treatment strategies in patients with low grade Non-Hodgkin's
Lymphoma. Correlation of genetic aberrations and immunologic marker profiles to
histopathological entities and the clinical course has lead to a new
transatlantic lymphoma classification. Today, application of 6-8 courses of
moderately intensive induction polychemotherapy induces partial or complete
remissions in 80% of patients in stage III or IV. Longterm maintenance therapy
with interferon alpha significantly prolongs progression free survival. Current
multicenter trials evaluate the curative potential of high-dose chemotherapy with
autologous stem cell transplantation. Recently, several new approaches including
new cytostatic drugs, immunotherapy with monoclonal antibodies and gene therapy
with antisense oligonucleotides have been developed and have achieved remissions
in pretreated patients. In the future, intensification of chemotherapy and the
new treatment options may offer the potential for cure in patients with low
malignant Non-Hodgkins Lymphoma.
PMID- 9654988
TI - [Treatment strategy of high malignancy non-Hodgkin lymphomas].
AB - While radiotherapy is not justified as a single-modality approach in high-grade
non-Hodgkin's lymphoma, standard therapy consists of chemotherapy with the CHOP
regimen, which induces complete remissions in ca. 2/3 of the patients, with or
without additional radiotherapy. Since the majority of these remissions do not
last, dose escalations up to myeloablative ranges using hematopoietic stem cell
support are being evaluated especially in young patients with bad risk factors.
The trials of the German Non-Hodgkin's Lymphoma Consensus Trial group determine
the value of a consolidating high-dose chemotherapy in young patients with high
risk profile, while dose intensifications of the CHOP regimen by two-week
regimens and/or the incorporation of etoposide are being evaluated in all other
treatment groups.
PMID- 9654989
TI - [Infectious spondylodiscitis--an important differential diagnosis in backache].
AB - All cases of spondylodiscitis diagnosed in our hospital between January 93 and
April 96 have been analysed retrospectively. With regard to potentially severe
complications, spondylodiscitis is an important differential diagnosis of back
pain. In our results 50% of the patients had a positive bacterial culture either
from blood or tissue. No complication has been observed. The most relevant
diagnostic procedures are: determination of CRP, magnetic resonance imaging and
eventually computed tomography in combination with biopsy and blood cultures.
Magnetic resonance imaging is a very sensitive method for early stage
osteomyelitis. Antimicrobial therapy should be based on the result of culture and
sensitivity tests. An antibiotic with good penetration into bone is preferred.
PMID- 9654990
TI - [Overweight (obesity) from the psychiatric viewpoint and its relevance for
general practice].
AB - Obesity is of great importance for health and health economy. It often goes along
with immense subjective and objective suffering. It has traditionally been a
topic of general and internal medicine. This article summarizes results derived
from recent psychiatric and psychotherapeutic approaches, that may also be of
interest for the somatic physician as they contribute to the understanding and
therapeutic management of the disease. Common definitions of obesity and
epidemiologic data are presented. Traditional therapeutic approaches such as
reducing diets often turned out to be insufficient. New knowledge, especially on
ponderal and nutritional physiology (set point theory of body weight,
investigations of dietary effects), studies about comorbidity with disturbed
eating habits (particularly binge eating and bulimia) and about psychodynamics
and life quality are expected to contribute to a better understanding of this
phenomenon.
PMID- 9654991
TI - [Intestinal paralysis in long-term diabetes mellitus].
AB - A 74 year old patient with diabetes mellitus was hospitalized because of nausea,
recurrent vomiting and increasing fatigue. Shortly before admittance the patient
had diarrhea. He also reported a recent onset of aversion against meat
consumption. Clinical investigation revealed a possible right-sided paraumbilical
abdominal tumor, normal bowel sounds, a vascular bruit and a normal white blood
count with increased band forms. During hospitalisation the general condition of
the patient deteriorated rapidly with fever and increasing numbers of immature
granulocytes. The patient finally died under the symptoms of a paralytic ileus
with hypotonia and hypoglycemia. Autopsy revealed a fist-sized stenosing tumor in
the cecum with the histology of a mainly well differentiated, cylindrocellular
adenocarcinoma. As immediate cause of death a bilateral paracentral lung embolism
with pulmonary edema was found, the latter probably as immediate consequence of
preterminal heart failure.
PMID- 9654992
TI - [Reversible dementia].
AB - A 65 year old woman, referred for differential diagnosis of dementia, presented
with cognitive and mnestic deficits. Typical signs and symptoms of hypothyroidism
led to the diagnosis of severe autoimmune thyroiditis. After six months of
treatment with thyroid hormone, dementia, myopathy and ataxia had disappeared.
The neurologic and neuropsychologic manifestations of hypothyroidism are
discussed. In dementia the diagnosis of secondary and reversible forms is of
great importance with regard to prognosis and treatment. Hypothyroidism is known
to be a common and treatable cause of pseudodementia. Early diagnosis and
adequate treatment are important to prevent further permanent deterioration of
cerebral function.
PMID- 9654993
TI - [Recurrent bronchitis. Kartagener syndrome].
PMID- 9654994
TI - [Chronic diarrhea and recurrent pulmonary infection. Variable
hypogammaglobulinemia].
PMID- 9654995
TI - [Fibromyalgia (generalized tendomyopathy) in expert assessment].
PMID- 9654996
TI - [Molecular biology and multifunctional aspects of nm23/NDPK].
PMID- 9654997
TI - [Stress response and molecular chaperones].
PMID- 9654998
TI - [Double stranded RNA-activated protein kinase (PKR): the role in signal
transduction and apoptosis].
PMID- 9654999
TI - [Physiological functions of programmed cell death].
PMID- 9655000
TI - [New aspect of neuron-specific proteins, synucleins and PNP 14, in
neurodenerative diseases].
PMID- 9655001
TI - [Autonomic regulation of melatonin synthesis through intrinsic glutaminergic
systems in mammalian pineal glands].
PMID- 9655002
TI - [Identification of organ-specific autoantigen in Sjogren's syndrome].
PMID- 9655003
TI - [Osteoclastogenesis inhibitory factor (OCIF)].
PMID- 9655004
TI - [Incidence of operations in Switzerland related to insurance status].
AB - Several studies reported in the literature show that surgical procedures can be
carried out for other than clinical indications. In Switzerland, no statistics on
the "demography" of surgical procedures are available. But an earlier analysis of
the "Swiss Health Survey 1992/93" gave first indications on differences in rates
of surgical procedures (hysterectomy, appendectomy, tonsillectomy and operation
of the hip and gallbladder) by sex, educational status and region. This study,
based on the same datasource (N = 10792), reveals an additional link with the
health insurance status. The prevalence of surgical procedures is higher in
privately insured than in persons with only basic insurance, independent of age,
sex and region. The highest rates of surgical procedures (except tonsillectomy)
are found among privately insured persons with a low educational status. Among 25
74 year old privately insured women, the lifetime-prevalence of a hysterectomy is
30% with low and 13% with high educational status (p < .001). The corresponding
prevalences of at least one of the mentioned surgical procedures (without
tonsillectomy) are 49% versus 28% (p < .001). As these are lifetime-prevalences,
these rates do not necessarily reflect the actual surgical procedures. However,
an analysis of the period of operation for hysterectomy and for the gallbladder
shows the same pattern as the mentioned lifetime-prevalences. Higher rates among
privately insured are also a frequent finding in the international literature.
These findings should stimulate patients to ask for a "second opinion".
Furthermore, there is an urge for the implementation of general hospital
statistics to verify such findings. In addition, the scientific consensus on the
indication of several surgical procedures should be promoted on the way to more
evidence-based-medicine.
PMID- 9655005
TI - How to do it: aortic and mitral valve replacement through aortotomy.
AB - Combined replacement of the aortic and mitral values is a relatively common
operation. Occasionally it is feasible to replace the mitral value through the
aortic root. This remarkable approach eliminates the need for a second atrial
incision, and in reoperation it avoids extensive dissection and release of
adhesions. Injury to the heart is minimized and the incidence of perioperative
bleeding is reduced. The exposure is excellent and the operation is performed
safely and expeditiously.
PMID- 9655006
TI - [Surgical diagnosis and therapy in patients with mediastinal space-occupying
lesions. A retrospective analysis of 223 intervention with special reference to
long-term course].
AB - The diagnostic and therapeutic approach in patients with mediastinal masses (MM)
treated at our institute between 1983 and 1993 was retrospectively reviewed.
METHODS AND MATERIAL: 193 patients with MM (105 males and 88 females, average age
53, ranging from 16-81) underwent 223 interventions. Staging mediastinoscopies in
lung cancer patients were ruled out. Long-term follow-up data were available in
123 of 162 cases with neoplastic MM (average follow-up time 5.5 years). Of all
223 surgical interventions 143 were diagnostic (53 parasternal mediastinotomies,
78 mediastinoscopies and 8 thoracoscopies) and 80 therapeutic (46 sternotomies
and 34 posterolateral and a second half). The analysed period was splitted up in
a first half (1983-1987) and second half (1988-1993) to study an eventual trend
in the management of MM. RESULTS: The most frequent diagnoses were: thymoma
(21%), malignant lymphoma (18%) and mediastinal sarcoidosis (14%). 43% of the MM
were localized in the anterior, 46% in the middle and 7% in the posterior
mediastinum. Thoracic pain, cough and dyspnoea represented the most common
symptoms, leading to an invasive diagnostic procedure. 25% of the patients had no
symptoms. The mortality and morbidity rate of all interventions was 3.4% and
18.7% respectively and concerned almost nerval injuries and postoperative
respiratory failure. The percentage of direct tumor excisions increased from 21%
during the first half of the period to 40% during the second half of the period,
whereas diagnostic surgical interventions decreased from 57% to 44%. The
percentage of total excisions after previous surgical biopsies decreased from 22%
to 16%. In spite of the introduction of high resolution CT scan and MRI
techniques during this time period no significant change in the use of
presurgical diagnostic procedures was obvious. Fine needle biopsies and
bronchoscopies were performed less frequent in the second half in comparison to
the first half (11%, 7%, 29%, 13% respectively). From 123 patients with
neoplastic disease data were available for long-term results. 35 had benign and
83 malignant histologies, in five cases dignity was unclear. 54% of these
patients were disease-free at follow-up time, 10% had local recurrency or distant
metastasis and 37% died during the observed time period. CONCLUSIONS: Surgical
biopsy seems to remain the most important investigation for a successful
interdisciplinary approach to MM. Overall morbidity and mortality rate of
mediastinal surgery might appear remarkable but has to be related to the favorous
long-term results after different individual treatment modalities in patients
with mediastinal masses.
PMID- 9655007
TI - [Supragenicular bypass: venous in comparison with synthetic prosthesis (PTFE)].
AB - In the time between 1984 and 1991 we have performed 136 infrainguinal arterial
reconstructions to the supragenicular popliteal artery for lower extremity
ischemia. We inserted in 98 cases the greater saphenous vein and in 38 cases a
PTFE-prosthesis. Life-table primary patency rate at 5 years was 88% for the vein
and 60% for the PTFE-grafts. Limb salvage results at 5 years were 92% and 76%. In
our experience patency rates with PTFE are inferior compared with vein grafts
even with distal anastomosis to the supragenicular popliteal artery. If we have
to bypass we preferentially use the greater saphenous vein even in this position.
"We do the best operation first".
PMID- 9655008
TI - [Allo-transfusion saving measures in maxillofacial surgery].
AB - In terms of a prospective clinical study between June 1994 and May 1996, in 204
patients undergoing maxillo-facial surgeries with a expected blood loss of more
than 500 ml a protocol of bloodsaving measures was followed. By means of an
additional retrospective study, the consumption of homologous blood and the
amount of bloodsaving measures between June 1990 and May 1994 was evaluated.
Bloodsaving measures were consisting from acute normovolemic hemodilution,
controlled moderate hypotension, cell saving, preoperative autologous blood
donation, and administration of rh-erythropoetine. The methoda were applied
isolated as well as in combination. Special concerns were given to a stable
intraoperative homeostasis and to the acceptance of a low hematocrit
perioperatively. Aim of the study was to investigate if, following the protocol,
even in major maxillofacial procedures homologous blood transfusions almost
completely can be avoided. Out of the 204 patients in the prospective study, only
30 received homologous blood. For the period June 94 to May 96, the reduction of
the number of patients receiving homologous blood in relation to the period June
90 to May 94 was 83%. The results indicate that in the years 94 to 96 twice as
much patients received bloodsaving measures. These led to a reduction of
homologous blood consumption for 427 units in 1990 to 56 units 1996 (p < 0.001).
If three measures, i.e. normovolemic hemodilution, cell saving, and hypotension
were combined, the need of blood transfusion was at the minimum level. The
effective reduction of homologous blood transfusion by consequent application of
bloodsaving measures can with these data obviously be demonstrated.
PMID- 9655009
TI - [A rare complication of permanent venous access: constriction, fracture and
embolization of the catheter].
AB - The pinch off syndrome due to squeezing of the implanted catheter is a rare
complication of permanent venous access devices (0.1 to 1% of the cases). The
cause is a mechanical catheter's compression in the costo-clavicular space, when
implanted too medially in the subclavian vein. In case of lack of venous reflux
or injection difficulties, sometimes complicated by local pain, a radiological
control must be obtained to demonstrate signs of compression or beginning of
fracture. Significant damage to the system is shown be extravasation of
radioopaque contrast medium. The suspicion of catheter damage justifies early
replacement of the system to avoid right heart or pulmonary artery embolism. The
electron microscopic scanning tends to prove that the catheter's rupture is
caused by a fatigue process.
PMID- 9655010
TI - [Early postoperative nutrition after laparoscopic and open colorectal resection].
AB - BACKGROUND: Discussions concerning postoperative nutrition were brought up again
with laparoscopic colorectal surgery. We are looking whether there is any
difference between open and minimal invasive procedures with respect to the start
of oral intake. METHODS: In a prospective controlled trial 152 patients were
analysed after laparoscopic (n = 85) or open (n = 67) colorectal resections. At
the first postoperative day fluid intake was unlimited and from the second day
regular food was permitted according to the patients desire. RESULTS: No
influence on the beginning of nutrition was by age, diagnoses, type of operation
nor their duration. Wound infection and specially cardiopulmonal decompensation
prolonged lack of appetite, however, not a pneumonia. There was no increase of
anastomotic leak rate. At day 4, a highly significant difference was found
between laparoscopic and open surgery with 90% and 60% of patients having started
regular nutrition (p < 0.001). CONCLUSION: Early postoperative oral nutrition
does not increase complication rate. Patients after laparoscopic procedures start
earlier eating compared with those after conventional surgery. We recommend early
postoperative oral intake after both techniques according to the patients desire.
PMID- 9655011
TI - [Submucous lipoma of the colon--report of 2 cases].
AB - Gastrointestinal lipomas are benign but rare lesions, mainly located in the
colon. Depending on their size they are responsible for obstructive bowel
symptoms. Diagnostic tools are either the endoscopy or computer tomography. It is
recommended to investigate the entire large bowel as other pathologies are often
found. Any lipoma found should be removed. Two cases with symptomatic lipoma are
presented. In both cases the lipoma was removed by open surgery.
PMID- 9655012
TI - Some effects of representational friction, target size, and memory averaging on
memory for vertically moving targets.
AB - Observers viewed an animated ascending or descending target that varied in size
and velocity across trials and appeared either (a) in isolation, (b) to slide
along one side of a single larger stationary object, or (c) to slide between two
larger stationary objects. Targets vanished without warning, and displacements
(i.e., differences between actual and remembered final position) along the axis
of motion and orthogonal axis were measured. Forward displacement (a) decreased
with increases in implied friction, (b) increased with increases in target size
for descending targets, and (c) decreased with increases in target size for
ascending targets. When a larger stationary object was to one side of the target,
orthogonal displacement was toward that object; when no object or objects on both
sides were present, orthogonal displacement was near zero. Results are consistent
with previous findings and speculation on the effects of representational
friction, memory averaging, and target size on memory.
PMID- 9655013
TI - The effect of spatial attention on memory scanning.
AB - Participants responded to probe letters after sets of two, four, and six letters
were memorized (Sternberg, 1966, 1969b). Spatial attention was controlled by
central arrow cues and stimuli were presented in a clear or a visually degraded
from. Overall RT was shorter for attended than for unattended locations, and
shorter for clear than for degraded stimuli. Even though the function relating RT
to memory-set size for stimuli in attended locations had a significantly smaller
zero-intercept than the function for unattended locations, she slope was
unchanged, which suggests that attention did not influence the memory-scanning
stage. Visual quality interacted with attention, which suggests that they
influenced the same stage of processing, presumably the early visual-encoding
stage of processing.
PMID- 9655014
TI - Display duration and stereoscopic depth discrimination.
AB - We investigated the role of display duration in stereoscopic depth perception.
The display consisted of a dynamic random-dot stereogram, with two disparity
defined squares (1.9 degrees x 1.9 degrees), one on the left and one on the right
of a central (Nonius) fixation stimulus. The sign of the disparity (crossed or
uncrossed) was always the same for both squares, and the magnitude of disparity
was 0.25 degree for one square and either 0.125 degree or 0.375 degree for the
other square. Participants indicated which square appeared closer. The display
duration was varied adaptively between 20 and 1000 ms until participants
performed at 75% accuracy. Results confirmed large individual differences in the
display duration required for stereoscopic depth perception. Approximately half
of the 100 naive participants were able to perform the task at 20 ms, while the
remaining participants required up to 1000 ms to perform at criterion. The
present study shows that display duration is a critical variable in explaining
wide differences in reported abilities of individuals to process stereoscopic
depth information.
PMID- 9655015
TI - Host mechanisms in the pathogenesis of periodontal disease.
AB - Periodontal diseases present with a wide range of clinical variability and
severity. Individual susceptibility seems to be of major importance in
determining the manifestation and progression of the disease. A better
understanding of the molecular mechanisms of action of the immune system is of
paramount importance to our ability to prevent and treat occurrence and
recurrence of periodontal diseases. Recent advances in immunobiology are very
promising for the identification of special categories of patients at risk for
periodontal breakdown. This review discusses the most recent studies in this
field and the possible clinical applications of recent advances.
PMID- 9655016
TI - Crevicular fluid biomarkers of oral bone loss.
AB - The lack of predictive value in periodontal disease detection has stimulated
intense research efforts in the development of diagnostic tests. Present
methodology using periodontal probes or radiographs to determine disease
susceptibility fails to allow an accurate periodontal risk assessment. The
analysis of gingival crevicular fluid components offers great potential as a
source of factors that may be involved in active periodontal bone loss. Over the
past decade investigators have begun to identify several molecules associated
with active periodontal tissue destruction. Recent advances in orthopedics and
osteoporosis have provided new biochemical markers of bone resorption, including
oral bone loss. The development of new diagnostic test strategies that target the
analysis of bone-specific markers offers great promise to accurately assess
active disease.
PMID- 9655018
TI - Relationship of diabetes to periodontitis.
AB - Although the relationship between diabetes and periodontal disease has been the
subject of much debate, the consensus of recent studies is that diabetic patients
have an increased risk of periodontal disease, particularly when metabolic
control is poor. This paper reviews recently published studies in this area and
concludes that not only is metabolic control a risk factor in disease
susceptibility but that it may also influence the outcome of periodontal therapy.
PMID- 9655017
TI - Association of the oral flora with important medical diseases.
AB - Recently, there have been case-control and epidemiologic investigations that
strongly associate poor dental health with cardiovascular disease, preterm low
birth weight infants, and early death from any cause. In a 7-year prospective
study, dental disease was a significant predictor of coronary events leading to
death after controlling for known coronary disease risk factors. Missing teeth
displaces smoking as a risk factor for ischemic heart disease in another study.
Periodontal disease was seven times more likely to be associated with a preterm
delivery of a low birth weight infant than mother's age, race, number of live
births, and use of tobacco or alcohol. This review examines the role of
asymptomatic bacteremia as possibly explaining these associations, focusing on
the bacterial load on the teeth as mediated via oral hygiene.
PMID- 9655019
TI - Systemic antibiotic therapy in severe periodontitis.
AB - The main goal in the treatment of periodontitis is to control the subgingival
infection. Systemic periodontal antibiotic therapy aims to reinforce mechanical
debridement procedures and to support the host defense system in overcoming the
infection that remains after conventional mechanical treatment. In particular,
patients with early onset periodontitis and patients with refractory
periodontitis may benefit from systemic antimicrobial therapy. Outside clinical
parameters, the use of microbiologic information can assist in selecting the most
optimal antibiotic regimen based on the presence and levels of selected
periodontal pathogens.
PMID- 9655020
TI - Periodontal pocket irrigation as adjunctive treatment.
AB - The emphasis in periodontal treatment generally has shifted in recent years from
periodontal surgery towards periodontal medicine. Because the major periodontal
disease group is the chronic inflammatory group, and the major direct cause of
chronic inflammation is dental plaque, much of the new research is directed at
more ergonomic and economic means of plaque control that have the efficacy of
traditional methods. As a result, the field of plaque chemotherapy is expanding
concurrent with the modes of application of anti-plaque chemical agents to their
interdental and subgingival sites of intended action. Since the rediscovery of
subgingival irrigation some 15 years ago, the technique has been shown to provide
an efficient means of subgingival application of anti-plaque agents, and it has
also been used to apply anti-inflammatory compounds. It was never intended to
stand alone. It was and is meant to be used as an adjunct to professional
debridement, but one that simplifies home-care oral hygiene for the patient.
This, indeed, is part of the aim of all chemical anti-plaque adjunctive therapy.
It requires the use of appropriate anti-plaque agents in sufficient concentration
and with sufficient periodicity to be clinically effective. It is only
ineffective if dose or periodicity is inadequate, or if mechanical plaque control
is unrealistically good--that is, unlikely to be maintained long term by the
majority of patients. Subgingival irrigation enables the patient for the first
time to deal with bursts of periodontitis activity when professional help is not
readily available. Although irrigation per se may dilute plaque toxins, it is
still clinically inadequate without a suitable chemical adjunct. Subgingival
irrigation with a suitable antimicrobial agent currently constitutes an effective
adjunct to the simplified oral hygiene regimen that does not require unrealistic
levels of interdental or subgingival home-care cleaning by the patient.
PMID- 9655021
TI - Nonsteroidal anti-inflammatory drugs as adjuncts in the management of periodontal
diseases and peri-implantitis.
AB - For the past three decades, prostaglandin E2 and other arachidonic acid
metabolites have been recognized as important proinflammatory mediators in bone
resorption and various forms of periodontal disease. Nonsteroidal anti
inflammatory drugs are chemical compounds that selectively inhibit the synthesis
of metabolites of the cyclooxygenase pathway, thereby blocking the production of
prostaglandins, thromboxane, and prostacyclin. Inhibiting prostaglandin E2
synthesis with nonsteroidal anti-inflammatory drugs has been unequivocally shown
in both animal and human studies to be of primary therapeutic efficacy. Recent
lines of nonsteroidal anti-inflammatory drugs research have focused on the
development of daily topical administration forms such as gels, toothpastes, and
rinses. Furthermore, new studies have implicated prostaglandin E2 in the peri
implantitis process, opening the possibility to manage failing implants with
topical nonsteroidal anti-inflammatory drug delivery systems.
PMID- 9655022
TI - Prevention and treatment considerations in patients with drug-induced gingival
enlargement.
AB - Drug-induced gingival overgrowth is an iatrogenic disease caused by the use of
phenytoin, cyclosporine, nifedipine, and other medications in the susceptible
patient. The gingival overgrowth can be due to three causes: noninflammatory,
hyperplastic reaction to the medication; chronic inflammatory hyperplasia; or a
combined enlargement due to chronic inflammation and drug-induced hyperplasia.
Drug-induced gingival enlargement can be minimized, but not prevented, by
elimination of local irritants, meticulous oral hygiene, and regular periodontal
recall. If gingival enlargement interferes with function, speech, esthetics, or
oral hygiene, tissue reduction can be accomplished by gingivectomy or a flap
procedure. Gingival enlargement may recur, especially in the patient with poor
oral hygiene.
PMID- 9655023
TI - Can surgery be justified for patients with periodontitis?
AB - There is a debate concerning the role that surgical procedures should play in the
treatment of inflammatory periodontal diseases. This review details some of the
situations in which surgery can be of benefit. Benefits include obtaining
shallower probing depths and therefore reducing the areas that are hospitable to
pathogenic bacteria associated with disease. Also, removal of tooth-accumulated
materials such as plaque and calculus in probing depths greater than 5 mm is more
predictable with surgery. In some forms of aggressive periodontitis, elimination
of potentially pathogenic bacteria is found more frequently with surgical
procedures. Regeneration of lost bone and attachment apparatus are predictable
only with surgery.
PMID- 9655024
TI - Long-term prognosis following resectional and regenerative periodontal
procedures.
AB - The ultimate goal of both resective and regenerative periodontal procedures is
the creation of soft- and hard-tissue architecture that is consistent with
periodontal health. Osseous resective procedures predictably produce minimal
clinical probing depth, but sacrifice periodontal support. An alternative method
to treat anatomic defects not easily managed through resection is guided tissue
regeneration (GTR). GTR provides clinicians with the opportunity to reverse the
disease-related loss of periodontal attachment. However, at present, the outcomes
of GTR procedures have not been shown to be predictable. Continued improvements
in techniques and materials, and identification of patient-related factors
significant to the success of the GTR procedures, should enhance the consistency
of the clinical outcomes. An evidence-based approach to the use of both
regenerative and resective therapies will enhance the clinical results achieved
through these procedures.
PMID- 9655025
TI - Clinical regeneration with guided tissue barriers.
AB - This review of the current periodontal literature evaluates clinical regeneration
with guided tissue barriers in infrabony defects and furcations. A meta-analysis
was conducted by calculating weighted means with confidence intervals for each
treatment group. Clinical improvement in infrabony defects was best for
polylactic acid/polyglactin (PLA/PGA) barriers, with a mean pocket reduction of
5.3 mm and a mean gain in clinical probing attachment level of 4.7 mm. For
furcations, special attention was given to the frequency of either complete or
partial (> or = 50%) furcation closure. Complete furcation closure was an
infrequent result of guided tissue regeneration, occurring in only 7% to 19% of
furcations treated with barriers. For the time period reported, the best clinical
results in furcations and infrabony defects occurred with PLA/PGA-type barriers.
However, there were no statistically significant differences among the various
barriers in infrabony defects or furcations.
PMID- 9655026
TI - Case selection and treatment considerations of guided tissue regeneration in deep
intrabony defects.
AB - Evidence reported in the period covered by this review, and here summarized with
a meta-analysis, indicated that guided tissue regeneration (GTR) management of
deep intrabony defects resulted in clinically significant and predictable gains
in tooth support. Controlled randomized clinical trials demonstrated that GTR
therapy was associated with significantly greater improvements in clinical
attachment than access flap procedures alone. A series of recent investigations
have also indicated that the magnitude and possibly the predictability of the
expected outcomes are dependent upon a variety of patient, defect, and procedure
associated factors. Substantial evidence has been provided that clinical
improvements obtained with GTR can be maintained over time.
PMID- 9655027
TI - Suture materials and techniques.
AB - Surgical improvements in periodontics have been achieved because of advances in
basic science, animal and clinical research, and the insight of outstanding
clinicians. Industry continues to develop new surgical materials, improving the
quality of sutures and needles and in turn, supporting advances in all surgical
specialties. The purpose of this article is to review sutures and suturing by
focusing on both materials and methods as they relate to the present practices of
surgical periodontics and dental implants.
PMID- 9655028
TI - An evidence-based approach to clinical practice guidelines in periodontics.
AB - The use of clinical practice guidelines has received considerable attention in
medicine and dentistry for improving clinical decision making and cost-effective
care. Leaders in dentistry are increasingly calling for improved standardization
of treatment through the development of clinical practice guidelines based on
empiric clinical evidence. Guidelines have been shown to minimize treatment
variability and ensure the quality and cost-effectiveness of care. Other
potential applications include educating individuals or groups; development of
quality indicators; improved allocation of resources such as insurance payment
decisions; and reduced risk of liability for negligent care. Recently, a series
of evidence-based clinical algorithms and practice guidelines were developed for
regenerative periodontal treatment. Such guidelines have the potential to improve
outcomes of periodontal care for providers, patients, and other interested
parties. This review discusses the rationale for guideline development and the
role of clinical practice guidelines in the area of periodontal decision making
and provision of care.
PMID- 9655029
TI - Do implant surfaces make a difference?
AB - The synthetic biomaterials commonly used as an interface or surface for soft- and
hard-tissue attachment and integration are commercially pure titanium, titanium
alloy (usually Ti6A14V), and hydroxyapatite. This review attempts to address the
following questions: Do the epithelium and connective tissue attach or adapt to
these synthetic surfaces? Is there a seal or just a cuff in terms of the soft
tissue interface? Is hydroxyapatite, commercially pure titanium, or Ti6A14V more
predictable and retentive? Is one better than the other or are all the same? Is
there an advantage of one surface over the other in terms of bone-to-implant
contact or shear strength when stressed? How about bone density and fixture
length; is one surface better than any other?
PMID- 9655030
TI - Localized bone reconstruction as an adjunct to dental implant placement.
AB - Advances in bone reconstructive techniques, including the potential of barrier
membrane usage for osteogenesis, have increased the indications for implant
placement. This review discusses the critical biologic and clinical criteria
involved in achieving a predictable success with barrier membranes. Experimental
and clinical findings have shown that the type of adjunctive grafting material
used, healing time of the membrane site, type and size of bone defect, and
membrane exposure all influence the end result. Small bony defects like implant
fenestrations and intact extraction sites seem not to depend on the application
of membranes to regenerate bone membranes. Large bone grafts used for ridge
reconstruction purposes might benefit from membranes, because they reduce the
inevitable resorption of bone grafts when used alone. New developments in
material and tissue engineering have introduced the use of resorbable membranes,
xenografts, and osteoinductive proteins, such as recombinant human bone
morphogenic protein, that are likely to play a role in the treatment of localized
ridge deficiencies.
PMID- 9655031
TI - Prosthodontic and periodontal considerations for implant-supported dental
restorations.
AB - In the past two years, many reports concerning the outcome of treatment using
dental implants have included more detailed data which allow insight into
prosthodontic and periodontal considerations that affect success. It has become
evident that unique biomechanical sequelae reflect the screw-joint character of
the dental implant prosthesis. The relative stability of the screw joint and the
biomechanical integrity of the components and prostheses themselves are new
issues to contend with for restorative dentistry. The biologic sequelae of
maintaining the implant-supported prostheses are revealed by bone maintenance and
peri-implant mucosal health. The microbiologic similarity of tooth and implant
associated plaque at inflamed sites suggests that infected teeth are sources of
potentially pathogenic bacteria at implants. However, the pathogenesis of
inflammatory disease at implants is not fully defined. The evaluation and
prognostic criteria of peri-implant inflammation remain controversial topics. The
present aggregate data indicate that the long-term evaluation of implant
supported dental prosthesis must be performed with cautious optimism and
attention to general biomechanical and biologic factors.
PMID- 9655032
TI - Etiology, diagnosis, and treatment considerations in peri-implantitis.
AB - Peri-implantitis is an inflammatory process affecting the tissues around an
osseointegrated implant in function, resulting in loss of supporting bone. A
review of the literature currently available leads to the conclusion that
microorganisms play a major role in this disease. Gram-negative anaerobic
bacteria, particularly fusobacteria, spirochetes, and black-pigmenting organisms
such as Prevotella intermedia are often found in diseased sites. Several
treatment modalities are presently being evaluated. Treatment aimed at a
reduction of the anaerobic bacteria improves clinical conditions. Furthermore,
case reports indicate a possibility for successful treatment with guided tissue
regeneration procedures. However, to date histologic evidence of true
reosseointegration has not been obtained. Incomplete surface decontamination
seems to be the major obstacle for regrowth of bone onto previously exposed
implants. It appears reasonable to attempt interception of destructive peri
implantitis as early as possible and to stop progression by removal of the
bacterial deposits.
PMID- 9655033
TI - Breath malodor.
AB - Breath odor research has recently received increasing attention from
periodontologists. Because a large portion of the adult population suffers from
gingivitis and eventually periodontitis, the etiologic factor in all cases at
risk must be considered. The first patient visit should, therefore,
systematically include examination of the paranasal cavities and throat to avoid
unnecessary time loss and frustration. Metabolic diseases and imaginary malodor
should also be considered. Not only the mere presence of a chairside volatile
sulfide monitor but also of that of an ear, nose, and throat specialist and
eventually a psychiatrist or psychologist who determines whether a breath odor
clinic merits its denomination. Volatile sulfur components are an important cause
of breath malodor but they are not the sole cause. This explains why organoleptic
and gas chromatographic diagnosis scores better than a portable sulfide monitor.
Other than etiologic therapy, masking can be achieved for a number of hours by
toothpastes containing a combination of triclosan and zinc chloride.
PMID- 9655034
TI - Treatment of orofacial pain and temporomandibular disorders.
AB - The treatment of orofacial pain and temporomandibular disorders has evolved into
a multidisciplinary approach using various modes of treatment and other medical
specialties as indicated. An excellent four-part, self-directed learning module
written by Goddard [1.], King [2.], Williams [3.], and Dean [4.] provides an
overview of accepted pain rehabilitation that includes basic science, chronic
pain, myofascial pain, cancer pain, and therapeutic options. An outstanding
review of the anatomy of the human temporomandibular joint is presented by Piette
[5.]. This brief review provides an update for the practitioner concerning recent
advances and research in the area of clinical treatment.
PMID- 9655035
TI - Supportive care of the periodontal patient.
AB - The ultimate goal of supportive periodontal care is to maintain health of the
dental and oral soft tissues. It represents a preventive measure for individuals
who have never experienced periodontal problems. On the other hand, supportive
care is a continuation of therapy for the treated periodontal patient, once
health has been reestablished. It aims at optimizing the results of therapy and
prevent further destruction following active treatment. Attempts are being made
to individualize and tailor supportive periodontal care according to the
patient's profile and needs. Recent trends also show increased use of
antimicrobials as adjuncts to mechanical procedures for controlling the etiologic
agents.
PMID- 9655036
TI - Field cancerisation in the head and neck.
PMID- 9655037
TI - Increased expression of epidermal growth factor receptor in normal epithelium
adjacent to head and neck carcinomas independent of tobacco and alcohol abuse.
AB - OBJECTIVE: In this study we examined if expression of the epidermal growth factor
receptor (EGFR) in normal epithelium adjacent to head and neck squamous cell
carcinomas (HNSCC) is increased and if this increase is due to the use of tobacco
and alcohol. MATERIALS AND METHODS: Cut sections of formalin-fixed and paraffin
embedded material of histologically normal epithelium adjacent to HNSCC from 25
patients who smoke excessively and abuse alcohol, and 17 HNSCC patients who do
not abuse tobacco and alcohol were compared with cut sections of normal
epithelium from 27 control individuals. The sections were immunohistochemically
stained for the EGFR. RESULTS: We show an elevation of the expression of the EGFR
in patients who smoke and drink excessively, that could also be ascertained, to a
lesser extent, in patients that do not have a history of smoking or drinking (P =
0.08). We also find that the closer the epithelium lies to the HNSCC the higher
the expression of the EGFR is. CONCLUSIONS: Expression of the EGFR is increased
in tumour-adjacent epithelium and this is not only due to the use of tobacco
and/or alcohol. We suggest that paracrine effects of the HNSCC and migration of
tumour cells may also play a role in this increased expression.
PMID- 9655038
TI - Bromodeoxyuridine incorporation and Ki 67 expression in oral hairy leukoplakia.
AB - OBJECTIVES: Oral hairy leukoplakia (HL) is an acanthotic, hyperparakeratotic
lesion characterised by the presence of a replicative Epstein-Barr virus (EBV)
infection in the superficial and adjoining layers of the epithelium. EBV or its
gene products are capable of modifying epithelial differentiation. The aim of
this study was to establish whether the presence of EBV was associated with an
alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation
and Ki 67 expression in lesional tissue and control mucosa. METHODS: Biopsies of
HL together with age, site and sex matched controls (n = 7 and 8 respectively)
were incubated in 200 microM BrdU in vitro, fixed in methacarn and processed to
paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were
identified in serial 5 microns sections using a three-stage immunoperoxidase
technique and cell density expressed as the number of positive cells per mm
basement membrane length. RESULTS: Overall, there was no difference in the number
of BrdU positive cells per mm basement membrane length between control and HL
tissue. However, within HL alone, the presence of focal EBV replication was
associated with a significant reduction in the number of basal cells
incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no
significant difference between Ki 67 positive cells in control and HL tissue and
no evidence of a reduction of Ki 67 positive cells in areas associated with EBV
replication. CONCLUSIONS: These results suggest that there is no evidence of a
generalised alteration of the proliferative capacity of basal cells in HL,
although the focal reduction in BrdU incorporation may reflect subtle changes on
cell turnover by EBV infection.
PMID- 9655039
TI - Association of cutaneous and oral diseases in HIV-infected men.
AB - OBJECTIVES: Mucocutaneous diseases are common in patients infected with human
immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV
infected people are at high risk, we sought those that are strongly associated
with specific HIV-related oral lesions and with progression of HIV disease.
DESIGN: A cross-sectional study of HIV-positive outpatients referred to a
university stomatology clinic for diagnosis and treatment of oral diseases. Each
subject underwent both complete oral and cutaneous examinations. RESULTS: Among
55 men, with a median age of 41 years and a median CD4 cell count of
125/microliter (range 0-950/microliter), 93% had active oral diseases or
conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma
(KS), and xerostomia, and 95% had skin conditions, including onychomycosis,
dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum
contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum
were associated with oral HIV-sentinel lesions (oral candidiasis, hairy
leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our
results suggest that xerosis and seborrheic dermatitis may be early harbingers of
HIV disease progression. Their roles as predictors warrant further study, based
on their associations with low CD4 cell counts and AIDS and strong co-prevalence
with one of the most common HIV-related oral lesions, oral candidiasis.
PMID- 9655040
TI - Resource implications for oral care of patients with HIV.
AB - OBJECTIVES: The aim was to investigate the attitudes of people with HIV infection
towards their own dental care provision and the possible implications for future
resource allocation. DESIGN: Sixty-nine HIV positive subjects attending support
groups in London were interviewed. Past and current dental visiting behaviour,
problems encountered in obtaining dental care and preferred site of delivery for
dental care were investigated. RESULTS: Showed that a majority (74%) changed
dentist or stopped attending following diagnosis with HIV, either due to fear of
or actual refusal of treatment, a desire to attend a more sympathetic dentist or
to attend a specialist clinic. Forty-five per cent withheld information about
their status. Subjects expressed a desire to receive regular dental care and had
definite preferences as to the site of delivery, 45% preferring general practice,
48% specialist clinics. CONCLUSIONS: Future resource allocation should be used
for continued support and education of general dental practitioners willing to
treat HIV positive patients, and for accessible specialist referral centres.
Hospital clinics could also provide regular routine care, especially in areas of
large HIV populations. An improved awareness of and access to community dental
clinics appears to be needed, with efforts focused on achieving an informed and
educated patient population through education programmes.
PMID- 9655041
TI - The frequency of fungal infection in biopsies of oral mucosal lesions.
AB - OBJECTIVE: To determine the frequency of fungal infection in biopsies of oral
mucosal lesions. MATERIALS AND METHODS: Histopathology reports issued between
1991-1995 inclusive were reviewed. During this period, a single section of each
mucosal biopsy had been stained using the periodic acid-Schiff (PAS) technique.
RESULTS: A total of 223 (4.7%) biopsies contained PAS-positive fungi: 191
individuals were affected, 124 (64.9%) of whom were male. There was a significant
(P < 0.01) positive association of fungal infection with moderate and severe
epithelial dysplasia, median rhomboid glossitis and squamous papillomas. Where a
subsequent biopsy was available, 21.9% dysplasias which were infected with fungi
worsened in histological severity, as compared with 7.6% of dysplasias which were
not infected at any stage. There was a significant negative association of fungal
infection with benign fibrous overgrowths (P < 0.01), benign hyperkeratoses,
lichenoid reactions and pyogenic granulomas (P < 0.05). The difference in
frequency of infection between the tongue and other sites was also significantly
higher (P < 0.01). CONCLUSIONS: There is a statistically significant association
between histologically-determined fungal infection and epithelial dysplasia, and
we recommend that a PAS stain be performed whenever oral epithelial dysplasia is
diagnosed, especially in male patients. On histological confirmation of
dysplasia, anti-fungal therapy should be considered in the management of these
lesions.
PMID- 9655042
TI - Age, gender, dentures and oral mucosal disorders.
AB - The numbers of participants over 75 years of age in previous studies of oral
health have not been sufficient to permit a full investigation of the influence
of age on the mouth. In this study a disproportionate stratified random sample of
255 independent elders was selected from a list of urban voters to provide
similar numbers of men and women in three age groups. The subjects were
interviewed and examined, and nearly half of them had mucosal disorders. There
was a significant (P < 0.05) association between mucosal lesions and the use of
dentures and tobacco, whereas stomatitis, denture-related hyperplasia and angular
cheilitis in particular were associated significantly with men and with the use
of defective dentures. Logistic regression revealed that neither age alone nor
the quality of dentures predispose to mucosal lesions, but that the odds of
finding stomatitis, denture-related hyperplasia and angular cheilitis in
particular increased about three-fold in denture-users, and almost doubled in
men.
PMID- 9655043
TI - Prevalence of oral lichen planus in diabetes mellitus according to the type of
diabetes.
AB - OBJECTIVE: The purpose of the present study was to determine the prevalence of
oral lichen planus (OLP) in a population of patients with diabetes mellitus (DM)
as compared with a control population. DESIGN: A clinicopathologic study.
SUBJECTS AND METHODS: One hundred and thirty-nine patients with type I DM, 353
patients with type II DM and 274 controls were examined for clinical evidence of
OLP. The clinical evidence of OLP in the diabetic and control patients was
confirmed by histopathological examination. RESULTS: The prevalence of OLP in
type I diabetic patients was 5.76%, in type II 2.83%, and 1.82% in the controls.
The prevalence of OLP was significantly higher in patients with type I DM and
slightly higher in patients with type II DM in comparison to the prevalence in
the control sample. CONCLUSIONS: The above findings and the fact that type I
diabetes and OLP are characterized by autoimmune phenomena and T cell immune
responses respectively, suggest that the immune system may play a critical role
in the appearance of OLP in patients with type I DM.
PMID- 9655044
TI - Surgical emphysema: an unusual complication of punch biopsy.
AB - Punch biopsies are frequently used in the diagnosis of oral disease and are
associated with few complications. We report a case of surgical emphysema
following this procedure.
PMID- 9655045
TI - The role of IL-6 in the pathogenesis of periodontal disease.
AB - The mechanisms underlying periodontal disease involve complex interactions
between bacterial products, host cells and locally produced, biologically active
factors. The umbrella term cytokine has been used to include a variety of such
factors, including the interleukin family. The role of one cytokine, IL-1 beta,
in periodontal disease pathogenesis has been widely reported. More recent studies
have focused on a potential role for IL-6 in driving the destructive processes.
Most of these reports have suggested a pro-inflammatory role for IL-6 alongside
IL-1 and TNF-alpha. This manuscript reviews the biological functions of IL-6,
specifically related to tissue destruction at the periodontal site. We would
suggest that the activity of IL-6 in periodontal disease differs from IL-1 and
TNF-alpha, and may, in part, play a protective role.
PMID- 9655046
TI - EU Working Group on Tobacco and Oral Health Consensus Meeting. Copenhagen, 23-26
October 1997. Abstracts.
PMID- 9655047
TI - Utilization of ceromer inlays/onlays for replacement of amalgam restorations.
AB - Fiber-reinforced Ceromer technology has been recommended for a variety of
restorations, including inlays/onlays, crowns and bridges, and direct
restorations. Ideal restorative dental materials must exhibit adequate physical
properties and fit, as well as ease and predictability of fabrication and repair.
The Ceromer restorative material combines the positive attributes of indirect
composite restorations, feldspathic ceramics, and cast-gold restorations. This
article reviews the material properties and aesthetic characteristics inherent to
Ceromers, as well as the appropriate preparation and adhesive techniques for
inlay/onlay restorations.
PMID- 9655048
TI - Bioaesthetic ceromer restorations for the replacement of existing posterior
amalgam restorations.
PMID- 9655049
TI - Aesthetic guidelines for second-generation indirect inlay and onlay composite
restorations.
AB - Recent innovations in indirect composite technology and adhesive bonding
procedures have resulted in the development of advanced materials particularly
suited for inlay and onlay restorations. Microhybrid composite resins are
characterized by a filler/matrix ratio that is significantly greater than that of
earlier materials. This article reviews the physical properties and clinical
application of these "second-generation" composite resins, with emphasis on a
system that utilizes a heat-curing process in conjunction with nitrogen pressure
to fabricate a material with improved mechanical and aesthetic properties.
PMID- 9655050
TI - Soft tissue punch technique for aesthetic implant dentistry.
PMID- 9655054
TI - Adhesive composite inlays for the restoration of cracked posterior teeth
associated with a tongue bar.
AB - While body piercing has become fashionable in contemporary society, numerous
health risks are directly related to this trend. Tongue piercing in particular
presents several concomitant complications for the attending clinician, including
the possibility of soft tissue infection or damage to the natural dentition or
existing restorations. Clinicians must be proficient in the selection of the
proper materials and techniques utilized to treat affected patients. This article
details a comprehensive clinical protocol for the use of adhesive composite inlay
restorations for cracked posterior teeth.
PMID- 9655055
TI - Pain as a motivator (Part II).
PMID- 9655056
TI - Looks can deceive.
PMID- 9655057
TI - Adhesive crowns and fixed partial dentures fabricated of ceromer/FRC: clinical
and laboratory procedures.
AB - Ceramic optimized polymer and fiber-reinforced composite materials represent a
significant development in prosthetic dentistry. When utilized in conjunction
with adhesive luting techniques, exceptionally conservative crown and bridge
restorations may be achieved. This article discusses utilization of these
materials in inlay and onlay restorations, as well as clinical and laboratory
procedures for fabrication, preparation, and seating of adhesive crown and bridge
restorations. The initial results of restorations utilizing these innovative
materials are presented.
PMID- 9655058
TI - Restoration of a posterior tooth utilizing a single-pontic FRC fixed partial
denture.
PMID- 9655059
TI - Root resorption of dental and traumatic origin: classification based on etiology.
AB - While root resorption is a relatively common complication of dental trauma,
classifications of root resorption are inconsistent and confusing. All
pathological root resorption of dental origin is inflammatory in nature. For root
resorption to occur, the protective superficial layer must be (internally or
externally) damaged or changed and an inflammatory stimulator must be present.
This article attempts to classify root resorption on the basis of etiology, i.e.,
the cause of the protective layer loss and the cause of the inflammatory
response, to facilitate more efficient treatment.
PMID- 9655060
TI - Adhesive dentistry: what's new beyond aesthetics.
PMID- 9655061
TI - Application of composite resin for single-appointment anterior and posterior
diastema closure.
AB - Due to aesthetic and periodontal factors, patients often seek treatment to close
diastemata. This condition may be eliminated by either direct or indirect
techniques. Indirect techniques generally require multiple visits to facilitate
the placement of laminate, crown, or bridge restorations, and involve significant
financial expense. Direct techniques can be economical and successful, although
they present unique challenges in the achievement of satisfactory proximal
contacts and contours. This article describes three clinical techniques that may
be employed to treat anterior and posterior diastemata in a single appointment.
PMID- 9655062
TI - Education and communication: now more than ever.
PMID- 9655063
TI - Principles of proximal cavity preparation and finishing with ultrasonic diamond
tips.
AB - Conventional treatment of proximal cavities can result in significant damage to
the adjacent dentition. This paper describes a recently developed technique of
proximal cavity preparation and finishing by use of selectively diamond-coated,
ultrasonically driven instruments. By using these instruments for composite,
compomer, ceramic, amalgam, and even gold restorations, the inadvertent damage to
neighboring teeth is completely avoided. This article demonstrates the effective
utilization of the diamond-tipped ultrasonic instruments for the preparation of
primary lesions and the replacement of existing restorations.
PMID- 9655064
TI - Mulling microdentistry.
PMID- 9655065
TI - In vitro and in vivo adhesion in operative dentistry: a review and evaluation.
AB - Dentin and enamel bonding agents (DBAs) were introduced in the early 1980s to
prevent volumetric shrinkage of composite resins used as restorative materials,
to ensure dentin and enamel marginal sealing, and to prevent the dislocation of
restorations during occlusal loading of the tooth. Today, DBAs play an important
role in cosmetic and aesthetic dentistry and have radically altered the
performance of operative dentistry. This article identifies the mechanical and
physical properties of DBAs that facilitate the bonding of enamel, dentin, and
various other restorations.
PMID- 9655066
TI - Pain management. Pain as a motivator (Part I).
PMID- 9655069
TI - Flowable composites: properties and applications.
PMID- 9655070
TI - Preparation and restoration of small interproximal carious lesions with sonic
instruments.
AB - Partially diamond-coated oscillating preparation instruments are particularly
suited for cutting minute interproximal cavities. This review presents an
oscillating preparation system with newly designed working tips for cutting and
finishing proximal microcavities. Analysis of the margins of various cavity
designs prepared with this instrumentation exhibited outlines that were
essentially free of defects. The method and instruments presented allow cutting
of minute first intervention cavities of interproximal lesions with defect
related extension. Enhanced margins can be attained without concomitant damage to
adjacent tooth surfaces.
PMID- 9655071
TI - Restoration of the maxillary arch utilizing a composite resin buildup and a fiber
framework.
PMID- 9655072
TI - Treatment options for the radicular lingual groove: a review and discussion.
AB - The radicular lingual groove (RLG) is a developmental anomaly in which an
infolding of the inner enamel epithelium and Hertwig's epithelial root sheath
create a groove that passes from the cingulum of maxillary incisors apically onto
the root. Radicular lingual grooves can create periodontal and pulpal pathology,
but they may be difficult to identify as an etiological factor. This article
identifies the diagnostic and treatment modalities for the various forms of RLGs
and describes the prognosis that can be anticipated with each treatment modality.
PMID- 9655073
TI - The cost of higher education.
PMID- 9655074
TI - Cost of dental education and student debt.
PMID- 9655075
TI - A primer on financial aid.
AB - It is apparent that financial aid is a complicated, ever-changing business. The
information provided in this article is only the tip of the financial aid
iceberg. As student debt levels continue to increase, I encourage deans to work
cooperatively with their financial aid officers. Invite your financial aid
officers to participate in orientation and other pre- and post-admission
activities, help facilitate effective entrance and exist interviews, and
encourage financial aid officers to meet and work with your students on a
frequent basis. I also strongly encourage you to support their participation in
national meetings such as the Professional Development Conference (PDC) for
Health Professionals (which AADS cosponsors with the AAMC) and the National
Association of Student Financial Aid Officers (NASFAA). Participation in annual
conferences is an important way for financial aid officers to network with other
officers and to learn about important new legislation.
PMID- 9655076
TI - Summary of federally funded loan repayment programs.
PMID- 9655077
TI - State-supported forgiveness programs.
PMID- 9655078
TI - Implications of changes in funding for graduate medical education.
PMID- 9655079
TI - The future of U.S. health care and its effect on health care education.
PMID- 9655080
TI - Evaluation of a computer-assisted test engine in oral and maxillofacial
radiography.
PMID- 9655081
TI - The central response to ovarian carcinoma simulates the response to sepsis.
AB - BACKGROUND: Animal models of stress and sepsis demonstrate increased hypophyseal
gene expression of the transcription factor c-fos and the cytokines interleukin-1
and interleukin-6. Chronic central nervous system exposure to interleukin-1
results in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia. We
test the hypothesis that the host response to ovarian carcinoma recapitulates the
host response to sepsis regarding the elaboration of the transcription factors
and cytokines in the central nervous system, liver, and lung. MATERIALS AND
METHODS: Nude mice were seeded intraperitoneally with either ovarian carcinoma
(MA-148) or vehicle. The animal subjects were observed for 5 weeks and sacrificed
for brain, pituitary, lung, and liver mRNA. We studied the mRNA accumulation of
the transcription factors c-fos, c-jun, and C/EBP alpha and the cytokines
interleukin-1 and interleukin-6 using reverse-transcriptase polymerase chain
reaction. RESULTS: Compared with the control, ovarian carcinoma in the mouse
model resulted in the following: (1) Pituitary c-fos and c-jun mRNA increased 3
fold (P = 0.012) and 6-fold (P < 0.001), respectively; (2) pituitary IL-1 and IL
6 mRNA increased 4-fold (P < 0.001) and 8-fold (P = 0.037), respectively; (3)
liver c-fos mRNA increased > 8-fold (P < 0.001); and (4) lung C/EBP alpha mRNA
decreased greater than 10-fold (P < 0.001). CONCLUSIONS: We conclude that the
host response to ovarian carcinoma in this animal model recapitulates many
aspects of the host response to bacterial sepsis especially concerning pituitary
gene expression. These data suggest that, as in sepsis, a hypothalamic
hypophyseal-mediated cytokine response in ovarian carcinoma may result in
hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia.
PMID- 9655082
TI - Clinical experience with cryosurgery for advanced hepatobiliary tumors.
AB - INTRODUCTION: There have been reports that suggest cryosurgical techniques may be
a useful adjunct to surgical resection or even a viable alternative treatment for
hepatobiliary malignancies. Our objective was to evaluate the clinical results
following cryoablation in conjunction with surgical resection for advanced
hepatic tumors. MATERIALS AND METHODS: Thirty-two consecutive procedures in 31
patients with advanced liver tumors treated with cryosurgical ablation were
evaluated. Cryosurgery was applied: (1) to achieve a > 1-cm tumor-free margin
when standard surgical margins were close (2) with or without standard surgical
resection to manage multiple tumors (3) with hepatic arterial portocath placement
to increase tumor response. Cryoablation was applied to 47 of 105 lesions-
independently in 4 patients and in combination with hepatic resection in 28
procedures. RESULTS: Cryoablation was used in 11 procedures because of close
surgical margins. In 21 operations cryosurgery was used for primary ablation. In
17 of these 21 patients both cryosurgery and resection were used for different
lesions; in 4 cryosurgery alone was used. Transient changes in hepatic enzymes,
PT, PTT, and platelets were at maximum on Postoperative Days 1-3. Surgical
mortality and morbidity rates were 6 and 60%, respectively. Coagulation
abnormalities were common: at least 30% reduction in platelets occurred in all
patients and greater than a 50% reduction occurred in 19 of 32 (59%). Twenty
patients had a PT > 15 s and 6 of these 20 also had a platelet count < 50,000.
Associated complications included one wound hematoma, two GI hemorrhages, one
intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site.
The actuarial patient survivals were 90, 59, 33, and 22% at 6, 12, 24, and 36
months, respectively. CONCLUSIONS: This report helps define the risks and results
of cryosurgical ablation as a complement to surgical resection for advanced
hepatobiliary tumors. Management of lesions contiguous to major blood vessels may
include either the Pringle maneuver or total vascular isolation. Since these
procedures can have significant morbidity, we urge cautious application of
cryosurgery for advanced hepatobiliary tumors in selected otherwise unresectable
patients.
PMID- 9655083
TI - Ischemia/reperfusion injury of the pancreas: a new animal model.
AB - BACKGROUND: Ischemia/reperfusion is thought to play an important role in the
development of postimplantation pancreatitis after pancreas transplantation and
also in the transition of edematous pancreatitis into necrotizing pancreatitis.
Previous studies have suggested that impairment of microcirculation and hence
tissue oxygenation and energy metabolism may be critical steps in this process.
MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail
was performed. Morphological alterations, tissue oxygenation, and energy
metabolism were assessed in response to 3 h of global warm ischemia and the
following reperfusion. RESULTS: A rapid onset of morphological alterations
immediately after reperfusion was noted. Oxygen consumption and ATP levels were
markedly decreased, and tissue oxygenation was severely impaired especially
during the first hour after reperfusion. ATP tissue levels and oxygen consumption
10 min after reperfusion correlated significantly with the morphological changes
at the end of the experiment. CONCLUSION: These findings can be explained by a
failure of nutritive capillary perfusion and concomitant shunt perfusion.
Therefore an impaired microcirculation rather than an impaired oxygen utilization
shortly after reperfusion is of major relevance in the development of the
ischemia/reperfusion injury of the pancreas.
PMID- 9655084
TI - Protection by cyclosporine A against normothermic liver ischemia-reperfusion in
pigs.
AB - BACKGROUND: Cyclosporine A (CYA) is primarily utilized as an immunosuppressant,
but its mechanisms of action (including decreased neutrophilic free radical
production and stabilization of mitochondrial and lysosomal membranes) may have
beneficial effects in ischemia and reperfusion (IR) injury. This study was
undertaken to examine the effect of CYA pretreatment on porcine liver
histopathologic changes and enzymatic release caused by ischemia and reperfusion.
MATERIALS AND METHODS: CYA was administered orally for 4 days prior to surgery in
two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs
were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion.
RESULTS: Significant decreases in AST levels compared to controls were seen in
high dose CYA pigs at the end of ischemia and at 30-min intervals during the
reperfusion period. Controls exhibited necrotic hepatocytes and severe
inflammatory cell infiltration, while high dose CYA animals demonstrated mild
inflammatory cell infiltrates. Controls had decreased survival--20% did not
survive reperfusion. CONCLUSIONS: This study indicates that CYA may be useful in
decreasing initial damage resulting from warm hepatic IR injury.
PMID- 9655085
TI - Nitric oxide inhibits peroxide-mediated endothelial toxicity.
AB - BACKGROUND: Oxidant molecules and nitric oxide (NO) have each been implicated as
mediators of endothelial cell damage, but the biologic effect of these molecules
acting in concert is incompletely understood. MATERIALS AND METHODS: We studied
the effects of an NO donor, S-nitroso-acetyl-D,L-penicillamine (SNAP), in
combination with the peroxidants tert-butyl hydroperoxide (TBH) and hydrogen
peroxide (H2O2) on rabbit aortic endothelial cells in culture. Cell viability was
assessed using Alamar blue, a nontoxic dye indicator of cell metabolism. Lipid
peroxidation was assessed using a chemiluminescent single-photon counting
technique. RESULTS: After 90 min exposure to test reagents, there was
concentration-dependent cytotoxicity for both TBH and H2O2. Peroxidant-induced
cytotoxicity was significantly ameliorated by SNAP (10(-4)-10(-3)M). N
Acetylpenicillamine and NO-depleted SNAP failed to demonstrate a cytoprotective
effect against peroxidant cellular injury, thus implicating NO as the agent
responsible for the protective effect. SNAP reduced lipid peroxidation caused by
10(-3) M TBH in a dose-dependent manner. Preincubation of cells with SNAP before
exposure to peroxidants alone had no effect on toxicity. CONCLUSIONS: NO is
cytoprotective to the endothelium in the presence of peroxidants through a
reduction of lipid peroxidation.
PMID- 9655086
TI - Myosin heavy chain expression in skeletal muscle autografts under neural or
aneural conditions.
AB - BACKGROUND: Our purpose was to investigate (1) the heterogeneity of satellite
cells derived from adult fast-twitch and slow-twitch skeletal muscles, (2) the
influence of innervation on muscle regeneration, and (3) the differences between
developmental myoblasts and satellite cells with regard to myosin heavy chain
(MHC) expression. MATERIALS AND METHODS: Autografts under neural (nerve-intact
graft; brief denervation interval) or aneural (aneural graft; prolonged
denervation interval) conditions of the fast-twitch extensor digitorum longus
(EDL) muscle or the slow-twitch soleus muscle were performed in adult rat
hindlimbs. MHC expression during skeletal muscle regeneration was determined
sequentially using immunocytochemistry. RESULTS: After grafting, most muscle
fibers in the EDL and soleus underwent ischemic degeneration and regeneration; at
the periphery of each muscle, a few adult fibers survived. All regenerating
fibers initially expressed embryonic/fetal (developmental) MHC alone, and
subsequently both developmental and fast MHC. During the first week, no
expression of slow MHC was observed in regenerating fibers in either the EDL or
the soleus. In nerve-intact grafts, regenerating fibers expressed slow MHC as
early as the second week; under aneural conditions, no regenerating fibers
expressed slow MHC even 4 weeks after grafting. On the other hand, some
persisting fibers in aneural grafts could maintain expression of slow MHC 4 weeks
after grafting; other fibers underwent MHC transformation induced by denervation.
No significant difference in MHC expression during regeneration was observed for
slow compared with fast muscles, under either neural or aneural condition.
CONCLUSIONS: These data suggest that regenerating adult skeletal muscle fibers,
derived only from satellite cells, cannot express slow MHC without motor
innervation, and that persisting muscle fibers, derived from both myoblasts in
fetal development and satellite cells, may be intrinsically distinct from
regenerating fibers. Satellite cells derived from slow and from fast muscles may
be a single, homogenous population and may be the same population as fetal
(secondary) myoblasts with regard to MHC expression.
PMID- 9655087
TI - Involvement of liver-associated immunity in hepatic metastasis formation.
AB - AIMS: Hepatic metastasis formation and prevention were studied from the viewpoint
of liver-associated immunity. METHODS: RCN-9, a colonic cancer cell line derived
from Fischer rats, and its subclone RCN-H4, in which the cancer is highly
metastatic to the liver, were used. Fischer rats that were inoculated with parent
RCN-9 colonic cancer cells (5 x 10(6)) via the portal vein showed liver
metastasis in less than 60% of the animals. In contrast, all rats (100%) that
received RCN-H4 produced multiple liver metastases. To investigate the difference
of hepatic metastasis formation, we assessed the susceptibility of both cell
lines against hepatic sinusoidal lymphocytes (HSL) by 51Cr-release assay, and the
expression of MHC class I and class II of both cell lines by flow cytometry. In
addition, we examined whether activation of HSL by interleukin-12 (IL-12) can
prevent liver metastasis of highly metastatic clone RCN-H4. RESULTS: The RCN-H4
clone showed decreased susceptibility to lysis by natural cytotoxic cells in HSL.
This decrease in cell susceptibility was attributable to an increase in cell
surface expression of MHC class I antigen. Administration of IL-12, a potent
NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4
clone and prevented liver metastasis of RCN-H4 inoculated into the portal vein.
CONCLUSIONS: Liver metastasis formation is positively correlated with the
strength of the hepatic immune system which mainly consists of ontogenetically
primitive T cells. As these effectors exert their cytotoxicity in a MHC
nonrestricted fashion, tumor cells that highly express MHC class I antigen can
readily avoid hepatic surveillance and apt to cause liver metastasis.
Augmentation of the hepatic immune system, for instance, with IL-12
administration, can prevent liver metastasis even in tumor cells with a high
potential for liver metastasis.
PMID- 9655088
TI - A rabbit model for metabolic studies after burn injury.
AB - BACKGROUND: A rabbit burn model was developed and characterized, which will allow
conduct of repeated, noninvasive and more sophisticated in vivo metabolic studies
to explore the pathophysiology of burn injury, owing to its larger blood volume
and tissue mass than the rat. MATERIALS AND METHODS: A 20% body surface, full
thickness burn was applied to the backs of six anesthetized rabbits by immersion
into a boiling-water bath for 10 s, followed by resuscitation with saline.
Resting energy expenditure (REE) was measured daily in pre- and postburn periods.
Whole body protein kinetics were evaluated using L-[1(-13)C]leucine tracer, on
the preburn and the third postburn day. Fasting plasma glucose was also measured.
RESULTS: A significant elevation of REE began on the second postburn day and
reached 34 +/- 8% above the preburn level (P < 0.05, paired t test) on the third
postburn day. The fasting plasma leucine flux and oxidation were significantly
elevated from their preburn levels (both P < 0.05), indicating an accelerated
proteolysis and a more negative body protein balance (P < 0.05); however, the
rate of whole body protein synthesis did not differ significantly pre- and
postburn injury. Fasting plasma glucose also increased (P < 0.001). on the third
postburn day. The burn scar remained intact during the study, without any sign of
infection. CONCLUSIONS: The metabolic changes observed in this animal model can
be attributed to burn injury per se and they mimic those for flow phase in burn
patients. This rabbit burn model should be suitable for exploring mechanistic
aspects of the burn-induced changes in metabolism and nutrient balance.
PMID- 9655089
TI - Evaluation of laser Doppler flowmetry to assess cyclosporine A-induced impairment
of renal blood flow.
AB - Cyclosporine A (CyA)-induced nephrotoxicity is a well-known complication of this
potent immunosuppressive drug. It is caused by an elevation in renovascular
resistance and impairment of renal blood flow. Currently, one of the principal
experimental settings to assess renal hemodynamics has been using the in vivo
fluorescent videomicroscopy (IVFV) method on hydronephrotic rat kidneys, which is
expensive, time-consuming, not physiological, and not applicable to humans. In
the present paper we have been able to confirm our working hypothesis that laser
Doppler flowmetry (LDF) is a valuable tool for assessing microcirculatory changes
in the rat kidney during CyA administration. Total subcapsular blood flow
decreased to approximately 70% of baseline values (P < 0.05) and mean arterial
pressure (MAP) increased initially to 113% of baseline values (P < 0.05) compared
to only minor changes for cremophor (carrier substance) or no changes for sodium
chloride solution 0.9%. LDF provides an easy and rapid technique and its major
advantage is the potential use in assessing microcirculatory changes after kidney
transplants in humans.
PMID- 9655090
TI - Phospholipase A2 activities are decreased during early but increased during late
phases of sepsis in rat heart.
AB - BACKGROUND: Changes in the activities of secretory phospholipase A2 (sPLA2) and
cytosolic phospholipase A2 (cPLA2) in the rat heart during early hyperdynamic and
late hypodynamic phases of sepsis were studied in an attempt to understand the
pathophysiology of cardiac dysfunction during sepsis. METHODS: Sepsis was induced
by cecal ligation and puncture (CLP). Experiments were divided into three groups:
control, early sepsis, and late sepsis. Early and late sepsis refers to those
animals sacrificed at 9 and 18 h, respectively, after CLP. PLA2 activity was
measured based on the rate of hydrolysis of 1-palmitoyl-2-[1-(14)C]-oleoyl
phosphatidylcholine. RESULTS: The results show that under physiological
conditions, sPLA2 and cPLA2 activities were time and protein dependent. The
optimal Ca2+ concentrations for sPLA2 and cPLA2 activities were 3 mM and 40
microM, respectively. During sepsis, sPLA2 activity was decreased by 25% (P <
0.01) during early phase while it was increased by 49% (P < 0.01) during late
phase of sepsis. Similarly, cPLA2 activity was decreased by 23% (P < 0.01) during
early sepsis while it was increased by 60% (P < 0.01) during late sepsis.
CONCLUSIONS: Since PLA2 functions to maintain cell membrane integrity and
function, a biphasic change in sPLA2 and cPLA2 activities may contribute to the
development of the two cardiodynamically distinct phases during the progression
of sepsis.
PMID- 9655091
TI - Visceral ischemia and neutrophil activation in sepsis and organ dysfunction.
AB - BACKGROUND: It has previously been shown that a rise in intraoperative neutrophil
CD11b expression during supracoeliac cross-clamping is a marker for subsequent
development of postoperative organ dysfunction. Prolonged visceral ischemia and
increased aneurysm extent are associated with higher risks of morbidity and
mortality after TAAA repair. This study investigates the relationship between
visceral ischemia and neutrophil activation in sepsis and organ dysfunction
following visceral reperfusion. METHOD: Fifty-one patients undergoing
supracoeliac cross-clamping, 5 patients undergoing suprarenal clamping, and 8
patients undergoing infrarenal clamping for repair of aortic aneurysms were
studied. Perioperative neutrophil CD11b expression was measured by flow
cytometry. RESULTS: There was significant correlation between visceral clamp time
and intraoperative CD11b expression. More extensive aneurysms resulted in
increased visceral clamp times and CD11b expression. There were no differences
between bypass and non-bypass-assisted surgery with regard to neutrophil
expression. There were increased clamp time in patients who developed severe
sepsis and postoperative organ dysfunction. Differences in preoperative levels of
CD11b expression were observed between groups and high levels of preoperative
CD11b expression were observed in patients who died intraoperatively, in type II
patients who went on to develop severe sepsis and organ failure, and in patients
who developed multiple organ failure rather than single organ failure.
CONCLUSION: Longer periods of visceral ischemia are associated with higher levels
of intraoperative CD11b expression, severe sepsis, and organ failure. High
preoperative levels of CD11b may identify an "at-risk" subset of patients.
PMID- 9655092
TI - Cardiopulmonary bypass primes polymorphonuclear leukocytes.
AB - Polymorphonuclear leukocyte (PMN) superoxide (.O2-) production has been
implicated in the pathogenesis of cardiopulmonary bypass (CPB)-related end organ
injury. PMN "priming" has been described as an event which enhances the release
of .O2- following a second, activating insult. We hypothesized that PMN priming
occurs during CBP and is temporally related to the plasma level of complement
(C3a), interleukin (IL)-6, and IL-8. PMNs were isolated from 10 CPB patients pre
bypass (preCPB), 5 min after protamine administration (PROT), and at 6 and 24 h
post-CPB. PMN .O2- production was measured by a cytochrome c reduction assay in
the presence or absence of either phorbol 12-myristate-13-acetate (PMA, 0.4
microgram/ml) or N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 microM) and
also after priming with 2000 nM platelet-activating factor (PAF) followed by
activation with either PMA or FMLP. Plasma levels of C3a, IL-6, and IL-8 were
determined by enzyme-linked immunosorbent assay. PMA-activated PMN .O2-
production was significantly elevated at 6 h post-CPB compared to pre-CPB levels
(11.04 +/- 0.9 vs 7.62 +/- 0.57, P = 0.009), indicating that CPB is associated
with in vivo PMN priming. When PMNs were primed in vitro with PAF and then
activated with PMA or FMLP, .O2- release at 6 h post-CPB was also significantly
greater than pre-CPB levels (16.04 +/- 0.74 vs 12.2 +/- 0.92, P = 0.038; and
17.33 +/- 1.38 vs 13.33 +/- 1.35, P < 0.05), indicating that CPB acts
synergistically with PAF to prime PMNs. Levels of C3a rose significantly over pre
CPB levels at PROT (P = 0.001), and IL-6 and IL-8 rose over pre-CPB levels at 6 h
post-CPB (P = 0.01 and P = 0.006, respectively). These findings demonstrate that
CPB not only directly primes PMNs, but also potentiates priming of PMNs by PAF.
This "primed" PMN state, which coincided with the increased plasma levels of
inflammatory mediators, may suggest a mechanism of predisposition to organ
dysfunction following CPB.
PMID- 9655093
TI - Hospital-wide educational program decreases red blood cell transfusions.
AB - BACKGROUND: Because of the numerous risks associated with the use of packed red
blood cells (RBCs), it is critical that they be transfused only when appropriate.
A hospital-wide educational program was developed in an attempt to improve the
transfusion practices and provide a framework for blood bank audit at a Veterans
Affairs teaching hospital. MATERIALS AND METHODS: The program required physicians
to fill out an information sheet that listed appropriate criteria for
transfusion. Charts were reviewed to determine if the transfusion met these
criteria. If the transfusion was deemed inappropriate by peer review, the staff
physician was notified by letter. The information sheet was used on a voluntary
basis without chart review in 1989 and on a mandatory basis beginning in 1990.
Transfusion rates and mortality were adjusted to patient days of hospitalization
and evaluated using chi 2 analysis. RESULTS: While voluntary use did not affect
transfusion rate, mandatory implementation resulted in a 26% decline (P < 0.001)
between 1989 and 1990 in the number of RBC units transfused per patient days of
hospitalization. A diminished use of RBCs persisted in the subsequent years.
There was no increase in mortality during this time to suggest a detrimental
effect from the decrease in RBC transfusion. No apparent variation in the
hospital population could account for the changes. CONCLUSION: Use of a unique
and simple transfusion request sheet as an educational tool resulted in improved
transfusion practices at a Veteran Affairs teaching hospital.
PMID- 9655094
TI - Comparative study of solutions for pulmonary preservation using an isolated
rabbit lung model.
AB - At the University of Minnesota, University of Wisconsin (UW), modified Euro
Collins (MEC), and Marshall (M) solutions were compared as agents for pulmonary
preservation in an isolated rabbit lung model. Normal saline (NS) was used as a
control. The heart-lung blocks of donor rabbits were flushed with, and then
preserved in, one of the solutions at 4 degrees C. Five rabbits were studied in
each group. After 8 h of cold ischemia, the left lung was ventilated and
reperfused with fresh venous blood from donor rabbits for 30 min. Pulmonary
function was assessed by serial measurements of oxygen (O2) and carbon dioxide
(CO2) tensions in blood obtained from the left atrial appendage. The ratios of
wet/dry (W/D) weight of the lungs were calculated to assess the extent of
pulmonary edema. After 8 h of preservation followed by 30 min of reperfusion, O2
tension was significantly higher with UW (178.36 + 1.72 mmHg). The calculated P
values were UW vs NS, < 0.0001; UW vs MEC, 0.154; and UW vs M, 0.0001. CO2
tension with UW was also lower than the other solutions: UW, 35.8 +/- 0.698 mmHg;
NS, 48.5 +/- 0.745 mmHg; MEC, 40.69 +/- 0.749 mmHg; and M, 44.68 +/- 0.697 mmHg.
The calculated P value was UW vs NS, 0.0001; UW vs MEC, 0.0003; and UW vs M,
0.0001 using repeated-measures analysis of covariance. The W/D ratio was lower
with UW as well; UW, 6.82 +/- 0.19; NS, 8.01 +/- 0.23; MEC, 7.28 +/- 0.10; and M,
7.34 +/- 0.17. The P value was < 0.001 using post-hoc tests. In this model, UW
solution preserved the lungs better than the other three solutions tested and
therefore warrants further clinical application.
PMID- 9655095
TI - Let's keep our eye on the sparrow.
PMID- 9655096
TI - Epiphyseal-metaphyseal enchondromatosis. A new clinical entity.
AB - We reviewed the cases of eight unrelated children who had an unusual form of
enchondromatosis characterized by unilateral enchondromas arising within the
epiphyseal and metaphyseal regions of the long tubular bones of the lower
extremity. Unlike previously described enchondromas, the lesions developed
extensively within the epiphysis before closure of the growth plate and there was
direct extension across the epiphyseal growth plate into the metaphysis. The
lesions resulted in severe limb-length discrepancy and angular deformity (which
increased in every patient after the time of presentation), asymmetrical
premature physeal arrest, and joint incongruity, all of which necessitated
numerous operative procedures. Seven patients had limb-lengthening and one had a
Boyd amputation without lengthening. Five patients had a second lengthening
procedure. Twenty-seven osteotomies (range, one to five procedures per patient)
were done; six patients had a repeat osteotomy. Four patients had an
epiphyseodesis. We believe that these lesions represent a previously undescribed
clinical entity, which we termed epiphyseal-metaphyseal enchondromatosis.
PMID- 9655097
TI - Distraction osteogenesis of the lower extremity with use of monolateral external
fixation. A study of two hundred and sixty-one femora and tibiae.
AB - We reviewed the results of distraction osteogenesis of 114 femora and 147 tibiae
that had been lengthened to treat a variety of diagnoses. The femora had been
lengthened an average of eleven centimeters (range, 3.5 to 17.0 centimeters), or
48 per cent (range, 8 to 86 per cent) of the original femoral length. The average
total time for the treatment of the femora (use of the fixator and any subsequent
immobilization) was 257 days (range, 105 to 420 days). There were 114
complications related to the femoral lengthenings, which led to eighty-seven
additional operations. The tibiae were lengthened an average of nine centimeters
(range, 3.0 to 15.6 centimeters), or 41 per cent (range, 9 to 100 per cent) of
the original tibial length. The average total time for the treatment of the
tibiae was 268 days (range, 110 to 497 days). There were 196 complications
related to the tibial lengthenings, which led to 219 additional operations. The
Achilles tendon was lengthened during or after seventy-three (50 per cent) of the
tibial lengthenings. The femoral lengthenings that were performed to treat a limb
length discrepancy were associated with significantly higher rates of
complications overall (p = 0.010) and additional operations (p = 0.023) for each
percentage of length gained than those that were performed to treat
achondroplasia or another skeletal dysplasia. The femoral lengthenings that were
performed to treat short stature (of an endocrine or idiopathic etiology) were
also associated with higher rates of complications overall and additional
operations than those performed to treat skeletal dysplasias, but the rates were
lower than those for lengthenings performed to treat limb-length discrepancy. The
rate of complications overall associated with femoral lengthening in patients who
were fourteen years old or more was significantly higher than that associated
with lengthening in patients who were less than fourteen years old (p = 0.047).
Femoral lengthening through the metaphysis was associated with significantly
higher rates of complications overall (p = 0.031) and additional operations (p =
0.042) for each percentage of length gained than femoral lengthening through the
diaphysis. The tibial lengthenings that were performed to treat Turner syndrome
and idiopathic short stature were associated with significantly higher rates of
complications overall (p = 0.026) and additional operations (p = 0.003) for each
percentage of length gained than those performed to treat skeletal dysplasias.
The rate of joint-related problems (p = 0.044) and that of additional operations
(p = 0.053) after tibial lengthening in patients who were fourteen years old or
more were significantly higher than those rates after tibial lengthening in
patients who were less than fourteen years old. The site of the tibial osteotomy
did not affect the rate of complications or additional operations. The femoral
healing indices (in terms of both days per centimeter [p = 0.002] and days for
each percentage of length gained [p = 0.019]) were significantly higher in the
patients who were fourteen years old or more than in those who were less the
fourteen years old. These values could not be used to predict an increase in the
complications because of poor bone formation. The results of the present review
suggest that the use of healing indices to gauge the final outcome of distraction
osteogenesis is questionable; we were unable to discern significance or clinical
importance from appropriately adjusted values.
PMID- 9655098
TI - Radiographic results of arthrodesis with Cotrel-Dubousset instrumentation for the
treatment of adolescent idiopathic scoliosis. A five to ten-year follow-up study.
AB - We evaluated the radiographic results of posterior spinal arthrodesis with use of
Cotrel-Dubousset instrumentation in seventy-six patients who had adolescent
idiopathic scoliosis. At an average of six years (range, five to ten years)
postoperatively, the fusion appeared to be solid in all patients. Comparison of
radiographs that had been made immediately postoperatively with those that had
been made at the time of the latest follow-up showed that no patient had lost any
correction in the coronal plane at the levels with instrumentation and seventy
five had had no change in the thoracic or lumbar sagittal alignment at the levels
with or without instrumentation. In the remaining patient, a kyphosis had
developed at the junction of the segments with instrumentation and those without
instrumentation, necessitating additional operative treatment. Sixty-three
patients completed a questionnaire for assessment of the clinical status. Their
responses were favorable with regard to function, cosmetic appearance, and
general satisfaction with the operative result. Twenty-four (38 per cent) of the
sixty-three patients reported occasional pain in the spine that did not interfere
with work or school activities. Sixty-two patients stated that, given the
hypothetical situation of reverting to the preoperative status, they would have
the operation again.
PMID- 9655099
TI - Percutaneous radiofrequency coagulation of osteoid osteoma compared with
operative treatment.
AB - Osteoid osteoma, a benign bone tumor, has traditionally been treated with
operative excision. A recently developed method for percutaneous ablation of the
tumor has been proposed as an alternative to operative treatment. The relative
outcomes of the two approaches to treatment have not previously been compared, to
our knowledge. The rates of recurrence and of persistent symptoms were compared
in a consecutive series of eighty-seven patients who were managed with operative
excision and thirty-eight patients who were managed with percutaneous ablation
with radiofrequency. Patients who had a spinal lesion were excluded. The minimum
duration of follow-up was two years. There was a recurrence, defined as the need
for subsequent intervention, after operative treatment in six (9 per cent) of
sixty-eight patients who had been managed for a primary lesion and in two of
nineteen who had been managed for a recurrent lesion. The average length of the
hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days
for those who had a recurrent lesion. There was a recurrence after percutaneous
treatment in four (12 per cent) of thirty-three patients who had been managed for
a primary lesion and in none of five who had been managed for a recurrent lesion.
The average length of the hospital stay was 0.2 day for these thirty-eight
patients. With the numbers available, we could detect no significant difference
between the two treatments with regard to the rate of recurrence. The rate of
persistent symptoms (that is, symptoms that did not necessitate additional
treatment) was greater than the rate of recurrence. According to responses to a
questionnaire, eight (30 per cent) of twenty-seven patients had persistent
symptoms after operative treatment and six (23 per cent) of twenty-six patients
had persistent symptoms after percutaneous treatment with radiofrequency. Two
patients had complications after operative excision, necessitating a total of
five additional operations. There were no complications associated with the
percutaneous method. The results of the present study suggest that percutaneous
ablation with radiofrequency is essentially equivalent to operative excision for
the treatment of an osteoid osteoma in an extremity. The percutaneous method is
preferred for the treatment of extraspinal osteoid osteoma because it generally
does not necessitate hospitalization, it has not been associated with
complications, and it is associated with a rapid convalescence.
PMID- 9655100
TI - Interrelationships of clinical outcome, length of resection, and energy cost of
walking after prosthetic knee replacement following resection of a malignant
tumor of the distal aspect of the femur.
AB - The relationships between the functional score according to the system of the
International Society of Limb Salvage, the extent of resection, energy cost of
walking, and gait characteristics were studied in thirty-six patients who had had
segmental knee replacement after resection of a malignant tumor of the distal
aspect of the femur. The mean free-walking velocity was 62.3 meters per minute
(79 per cent of normal), which was a result of decreases in both cadence and
stride length. The mean net energy cost during walking was 35 per cent greater
than that of normal controls and correlated with the percentage of the femur that
had been resected. All patients had decreased single-limb support time on the
affected side compared with the unaffected side. There was a weak correlation
between the asymmetry of the single-limb support time and the percentage of the
femur that had been resected. The mean extensor torque of the affected knee was
30 per cent that of the unaffected knee when one head of the quadriceps muscle
had been excised, 19 per cent when two heads had been excised, 4 per cent when
three heads had been excised, and 1 per cent when four heads had been excised.
The patients who had had an extra-articular resection had lower mean extensor and
flexor torques at the knee compared with those who had had an intra-articular
resection. The asymmetry of the single-limb support time was inversely related to
the residual extensor and flexor torques. The overall score according to the
system of the International Society of Limb Salvage ranged from 17 to 29 points
(mean, 24.6 points; 82 per cent of normal). The net energy cost, percentage of
maximum aerobic capacity, and asymmetry of the single-limb support time had
significant negative correlations with the overall functional score. Multivariate
analysis showed that the overall functional score and the percentage of the femur
that had been resected were the two most important factors that predicted the net
energy cost. To our knowledge, this is the first objective validation of the
functional score according to the system of the International Society of Limb
Salvage. As the net energy cost can be predicted from universally available,
inexpensive measures, investigators can easily use it as a clinical and research
tool to evaluate prosthetic performance and to assess operative outcome.
PMID- 9655101
TI - Arthroscopic repair of full-thickness tears of the rotator cuff.
AB - We present the results of arthroscopic repair of full-thickness tears of the
rotator cuff in seventy-three patients (thirty-nine men and thirty-four women).
The average age of the patients at the time of the operation was 60.7 years
(range, thirty-one to eighty-two years). All of the patients were followed for at
least two years (average, thirty months; range, twenty-four to forty months). The
shoulders were evaluated with the rating scale of the University of California at
Los Angeles, the shoulder index of the American Shoulder and Elbow Surgeons, and
the functional rating scale of Constant and Murley. In addition, the patients
completed the Short-Form 36 Health Survey (SF-36) preoperatively and at the
yearly follow-up evaluations. Eleven tears were small (less than one centimeter
in length), forty-five were medium (one to three centimeters), eleven were large
(more than three to five centimeters), and six were massive (more than five
centimeters). The average length of the tear was twelve millimeters, and the
average width was twenty-seven millimeters. Sixty-nine tendons were repaired
anatomically, and four were repaired an average of three millimeters (range, two
to eight millimeters) medial to the anatomical insertion of the tendon. An
average of 2.3 (range, one to four) suture anchors were used in the repair. Sixty
three glenohumeral joints were normal, and ten had an intra-articular lesion.
Seven patients had a concomitant resection of the acromioclavicular joint. The
average duration of the operation was fifty-six minutes (range, thirty-five to
ninety minutes). The active and passive ranges of motion improved significantly
after the procedure (p = 0.0001). The strength of resisted elevation improved
from 7.5 to 14.0 pounds (3.4 to 6.3 kilograms) (p = 0.0001). The average total
score according to the rating scale of the University of California at Los
Angeles improved from 12.4 to 31.1 points; the average total score according to
the shoulder index of the American Shoulder and Elbow Surgeons, from 30.7 to 87.6
points; and the average absolute score according to the rating system of Constant
and Murley, from 41.7 to 83.6 points (p = 0.0001 for all comparisons). The
average score for the pain component of the rating scale of the University of
California at Los Angeles improved from 2.4 to 8.6 points; fifty-seven (78 per
cent) of the seventy-three patients rated the relief of pain as good or excellent
on the visual-analog scale. The average score for satisfaction improved from 0.4
to 4.6 points; sixty-six patients (90 per cent) rated their satisfaction as good
or excellent at the time of the most recent examination. None of the shoulders
were rated as good or excellent before the operation, whereas sixty-one (84 per
cent) were so rated at the most recent follow-up evaluation after the index
procedure. In addition, significant improvements (p = 0.0015) were noted in the
scales and summary measures of the SF-36. Arthroscopic repair of full-thickness
tears of the rotator cuff produced satisfactory results with regard to
traditional orthopaedic criteria as well as with regard to patient-assessed
criteria such as satisfaction, pain relief, and general health. The arthroscopic
method offers several advantages, including smaller incisions, access to the
glenohumeral joint for the inspection and treatment of intra-articular lesions,
no need for detachment of the deltoid, and less soft-tissue dissection. However,
these advantages must be considered against the technical difficulty of the
method, which limits its application to surgeons who are skilled in both open and
arthroscopic procedures on the shoulder.
PMID- 9655102
TI - Long-term results of the Latarjet procedure for the treatment of anterior
instability of the shoulder.
AB - We performed ninety-five consecutive Latarjet procedures for the treatment of
recurrent anterior instability of the shoulder between 1969 and 1983. In 1993, we
retrospectively reviewed the clinical and radiographic results that were
available for fifty-six patients (fifty-eight shoulders) who had been followed
for an average of 143 years (range, ten to twenty-three years). The purpose of
the study was to determine the prevalence of glenohumeral osteoarthrosis and the
factors related to its development after the Latarjet procedure. The procedure
was performed for the treatment of recurrent anterior dislocation in fifty
shoulders and painful recurrent anterior subluxation in eight. All patients had a
radiographic evaluation (three anteroposterior radiographs, with the humerus in
external, neutral, and internal rotation, and one lateral radiograph) before the
operation and at the latest follow-up examination. At the time of the latest
follow-up, none of the patients had recurrent dislocation, six patients had
apprehension with regard to possible dislocation, and one had occasional
subluxation. According to the system of Rowe et al., fifty-one (88 per cent) of
the fifty-eight shoulders had an excellent or good result; five (9 per cent), a
fair result; and two (3 per cent), a poor result. Twenty-two shoulders had no
glenohumeral osteoarthrosis. Thirty-four shoulders had centered glenohumeral
osteoarthrosis (the humeral head remained in front of the center of the glenoid
cavity), which was grade 1 in twenty-five shoulders, grade 2 in four, grade 3 in
three, and grade 4 in two, and two shoulders had grade-4 eccentric glenohumeral
osteoarthrosis (the humeral head was more proximal than normal in relation to the
center of the glenoid cavity). Postoperative grade-1 glenohumeral osteoarthrosis,
unlike the higher grades, had no effect on the function of the shoulder.
PMID- 9655103
TI - Biomechanical effect of medial advancement of the supraspinatus tendon. A study
in cadavera.
AB - During the repair of some rotator-cuff tears, the torn tendon cannot be freed up
adequately to permit reattachment at its original anatomical site of insertion.
An option is to advance the site of insertion medially and reattach the tendon to
a trough in the sulcus or to the humeral head. The biomechanical effects of such
medial advancement on the moment arm of the supraspinatus muscle during
glenohumeral elevation were studied in ten fresh-frozen shoulders from cadavera.
Medial advancement of the site of insertion of the supraspinatus tendon was
simulated by the placement of suture anchors in the sulcus of the proximal part
of the humerus at points three, ten, and seventeen millimeters medial to the
junction of the supraspinatus tendon and the bone. These distances were chosen
not because they represent clinical options but because the large range allowed
biomechanical study of medial advancement. Nylon lines were attached to the
suture anchors and were passed back through an eyehook at the midpoint of the
supraspinatus muscle. The excursion of each line was measured as the humerus was
elevated, and the moment arm was estimated from the joint angle and excursion
data with use of the principle of virtual work. Three and ten millimeters of
medial advancement of the tendon (attachment in the sulcus) had a minimum (non
significant) effect on the moment arm during elevation compared with the value
determined for the intact condition. However, seventeen millimeters of medial
advancement was found to reduce the moment arm significantly (p < 0.05).
PMID- 9655104
TI - Revision total shoulder arthroplasty for the treatment of glenoid arthrosis.
AB - The development of painful glenoid arthrosis is the most common reason for
reoperation after replacement of the humeral head. We performed twenty-two
revision total shoulder arthroplasties, between 1983 and 1992, for the treatment
of painful glenoid arthrosis in shoulders that had a prosthetic replacement of
the humeral head. Eighteen shoulders (seventeen patients) were included in the
study as their preoperative and operative records were complete and they had been
followed for at least two years (mean, 5.5 years; range, 2.3 to 10.0 years). The
indications for the hemiarthroplasty were trauma (ten shoulders), osteoarthrosis
(four), rheumatoid arthritis (two), and osteonecrosis secondary to the use of
steroids (two). The mean interval between the hemiarthroplasty and the total
shoulder replacement was 4.4 years (range, 0.8 to 12.7 years). The mean score for
pain in the shoulder decreased from 4.3 points before the revision to 2.2 points
after it (p = 0.0001). The mean active abduction increased from 94 degrees before
the revision to 124 degrees after it (p = 0.01), and the mean external rotation
increased from 32 to 58 degrees (p = 0.007). Two shoulders needed another
operation after the revision because of a late infection in one and particulate
synovitis associated with instability in the other. With the numbers available
for study, we did not detect a significant difference in pain relief and range of
motion with respect to gender, diagnosis, subluxation, or the presence of
periprosthetic radiolucency. Our findings indicate that most patients with
painful glenoid arthrosis after a hemiarthroplasty have marked pain relief and
improvement in motion after revision to a total shoulder replacement. However,
seven of the eighteen shoulders that had this procedure had an unsatisfactory
result due to a limited range of motion or the need for a subsequent operation.
Therefore, long-term studies are necessary to evaluate the durability of total
shoulder replacement in this group of patients.
PMID- 9655105
TI - The influence of active shear or compressive motion on fracture-healing.
AB - The effects of interfragmentary sliding (shear) motion, axial motion, and locked
external fixation on the healing of mid-tibial closed fractures were studied in
fifty-six skeletally mature New Zealand White rabbits. The fractures were fixed
with use of a four-pin, double-bar frame and were allowed to heal for either two
or four weeks. Four experimental conditions were evaluated: transverse and
oblique fractures treated with a locked external fixator (Groups 1 and 3,
respectively), transverse fractures treated with an axially telescoping fixator
(Group 2), and oblique fractures treated with a sliding oblique fixator (Group
4). The maximum interfragmentary motion, recorded in vivo with an electronic
motion sensor that was attached to the fixator, was 0.6 millimeter in Group 2
during the first week and then declined rapidly. In contrast, the motion in Group
4 exceeded 1.5 millimeters during the first week. The circumference of the callus
in Group 4 was 11 to 23 per cent greater than that in the other groups at both
two and four weeks (p < or = 0.02). At two weeks, torsional stiffness, strength,
and energy absorption were comparable among Groups 1, 2, and 3. The increase in
healing was most rapid for Group 4; by four weeks, the torsional strength and
energy to failure of the fractures in Group 4 exceeded those in the other groups
(p < or = 0.025) and reached or exceeded those of intact bone. Apparently,
oblique sliding (shear) motion promoted greater cartilage differentiation and
expansion of the peripheral callus than did axial motion or locked external
fixation.
PMID- 9655106
TI - Radioulnar load-sharing in the forearm. A study in cadavera.
AB - Custom-designed miniature load-cells were inserted into the distal end of the
ulna and the proximal end of the radius in ten fresh-frozen forearms from
cadavera. The forces transmitted through the bones at these sites were measured
under 134 newtons of constant axial load that was applied through the metacarpals
as the forearm was rotated from 60 degrees of supination to 60 degrees of
pronation. The simultaneous measurements of these forces allowed the calculation
of radioulnar load-sharing at the wrist and the elbow as well as the calculation
of the amount of force that was transferred from the radius to the ulna through
the interosseous membrane. With the elbow in valgus alignment (that is, with
contact between the radial head and the capitellum), the main pathway for load
transmission through the forearm was direct axial loading of the radius;
measurements from both load-cells were unaffected by the angle of elbow flexion.
When the forearm was in neutral rotation, the mean force in the distal end of the
ulna averaged 2.8 per cent of the load applied to the wrist and the mean force in
the proximal end of the ulna averaged 11.8 per cent; this indicated that only a
small amount of tension developed in the interosseous membrane. With the elbow in
varus alignment (that is, with no contact between the radial head and the
capitellum), load was transmitted through the forearm by a transfer of force from
the radius to the ulna through the interosseous membrane. When the forearm was in
neutral rotation, the force in the distal end of the ulna averaged 7.0 per cent
of the load applied to the wrist and the force in the proximal end of the ulna
averaged 93.0 per cent; the force through the interosseous membrane decreased
with supination of the forearm. Testing with the elbow in valgus alignment and
shortening of the distal end of the radius in two-millimeter increments produced
corresponding increases in force in the distal end of the ulna and decreases in
force in the radial head. The forces through the interosseous membrane remained
low after each amount of radial shortening.
PMID- 9655107
TI - Fracture-dislocation of the humerus with intrathoracic displacement of the
humeral head. A case report.
PMID- 9655108
TI - Early detection of osteochondritis dissecans of the capitellum in young baseball
players. Report of three cases.
PMID- 9655109
TI - Hallux rigidus and osteoarthrosis of the first metatarsophalangeal joint.
PMID- 9655110
TI - The prospective, randomized, double-blind clinical trial in orthopaedic surgery.
PMID- 9655111
TI - A meta-analysis of the efficacy of non-operative treatments for idiopathic
scoliosis.
PMID- 9655112
TI - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
double-blind study.
PMID- 9655113
TI - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
double-blind study.
PMID- 9655114
TI - Resurfacing of the patella in total knee arthroplasty. A prospective, randomized,
double-blind study.
PMID- 9655115
TI - Recruitment curve of the soleus H reflex in patients with neurogenic
claudication.
AB - The diagnosis of neurogenic claudication (NC) remains uncertain when no definite
signs of radicular lesions are found in electrophysiological testing. However,
the functional deficit could be demonstrated during the brief time in which the
patients complain of pain and weakness in the muscles of the lower limbs after
walking. We have used electrophysiological testing of the H reflex and the F wave
to document the transient functional derangement expected to occur at the
radicular level in patients with NC after walking. We examined the recruitment
curve of the soleus H reflex, and the chronodispersion of the posterior tibial
nerve F wave, at rest and after a walking exercise that triggered their symptoms
in 10 patients with NC, with no positive electrophysiological findings of
radicular lesion. The same studies were performed in 5 age-matched healthy
volunteers, used as control subjects, who were asked to walk for 30 min. At rest
before walking, no abnormalities were found in any of the patients. After
walking, the H wave showed a transient increase in its threshold with respect to
that of the M wave in 7 patients (70%). Such abnormality lasted for a mean period
of 7 min. In 2 of these patients there was also an increase in the F-wave
chronodispersion. Our data suggest that nerve conduction is transiently blocked
in large myelinated fibers at a radicular level in patients with NC after
walking. Partial interruption of the H-reflex circuit could be one of the
pathophysiological mechanisms underlying NC.
PMID- 9655116
TI - Alternative dystrophin gene transcripts in golden retriever muscular dystrophy.
AB - Golden retriever muscular dystrophy (GRMD), the canine model of Duchenne muscular
dystrophy (DMD), is caused by a splice site mutation in the dystrophin gene. This
mutation predicts a premature termination codon in exon 8 and a peptide that is
5% the size of normal dystrophin. Western blot analysis of skeletal muscle from
GRMD dogs reveals a slightly truncated 390-kD protein that is approximately 91%
the size of normal dystrophin. This 390-kD dystrophin suggests that GRMD dogs,
like some DMD patients, employ a mechanism to overcome their predicted
frameshift. Reverse-transcriptase polymerase chain reaction on GRMD muscle has
revealed two in-frame dystrophin transcripts which lack either exons 3-9 or exons
5-12. Both transcripts could be translated into a dystrophin protein of
approximately 390 kD. An understanding of how truncated dystrophin is produced in
GRMD may allow this mechanism to be manipulated toward a potential therapy for
DMD.
PMID- 9655117
TI - Median and ulnar nerve conduction studies among workers: normative values.
AB - To determine normative values for nerve conduction studies among workers, we
selected a subset of 326 workers from 955 subjects who participated in medical
surveys in the workplace. The reference cohort was composed exclusively of active
workers, in contrast to the typical convenience samples. Nerve conduction
measures included bilateral median and ulnar sensory amplitude and latency (onset
and peak). Workers with upper extremity symptoms, medical conditions that could
adversely affect peripheral nerve function, low hand temperature, or highly
repetitive jobs were excluded from the "normal" cohort. Linear regression models
explained between 21% and 51% of the variance in nerve function, with covariates
of age, sex, hand temperature, and anthropometric factors. The most robust models
were fitted for sensory amplitudes in the median and ulnar nerves for dominant
and nondominant hands. The median-ulnar difference was least sensitive to
adjustment, indicating it is the best measure to use if corrections are not made
to account for relevant covariates. A key point was that the magnitude of
variance increased with age and anthropometric factors. These findings provide
strong evidence that to improve diagnostic accuracy, electrodiagnostic testing
should control for relevant covariates, particularly age, sex, hand temperature,
and anthropometric factors.
PMID- 9655118
TI - Longitudinal study of skeletal muscle adaptations during immobilization and
rehabilitation.
AB - This study describes the metabolic, morphologic, neurologic, and functional
adaptations observed in the plantar flexors during 8 weeks of lower leg
immobilization and 10 weeks of physical therapy following ankle surgery. A
combination of magnetic resonance imaging and spectroscopy, isokinetic and
isometric muscle testing, and simple functional tests revealed many adaptive
changes due to immobilization, including atrophy, loss of muscle strength,
reduced central activation, increase in fatigue resistance, and an increase in
inorganic phosphate content. After 10 weeks of physical therapy all alterations
were reversed, with the exception of a remaining 5.5% deficit in total muscle
cross-sectional area.
PMID- 9655119
TI - Electrophysiological determination of the site involved in generating abnormal
muscle responses in hemifacial spasm.
AB - In patients with hemifacial spasm (HFS), abnormal muscle responses due to
abnormal cross-transmission are observed in facial muscles. However, the site in
the facial nerve responsible for the cross-transmission remains a matter of
controversy. We have developed a model in which by considering the
electrophysiological parameters involved in producing the abnormal muscle
response, we can determine the site of the abnormal cross-transmission within the
facial nerve. This model was applied to HFS patients with three different
etiologies: idiopathic, post-Bell's palsy, and post-XII-VII anastomosis. Our data
show that: in idiopathic HFS, the cross-transmission may occur in the facial
nerve at the level of the pontocerebellar angle; in post-Bell's palsy, it is
inside the petrous bone; and in XII-VII anastomosis, it must be in the
extracranial part of the facial nerve. The possible mechanisms for this cross
talk are discussed in terms of ephaptic transmission or of a central
hyperexcitability in the facial motor nucleus.
PMID- 9655120
TI - Disruption and reorganization of sodium channels in experimental allergic
neuritis.
AB - The axonal distribution of voltage-dependent Na+ channels was determined during
inflammatory demyelinating disease of the peripheral nervous system. Experimental
allergic neuritis was induced in Lewis rats by active immunization. In diseased
spinal roots Na+ channel immunofluorescence at many nodes of Ranvier changed from
a highly focal ring to a more diffuse pattern and, as the disease progressed,
eventually became undetectable. The loss of nodal channels corresponded closely
with the development of clinical signs. Electrophysiological measurements and
computations showed that a lateral spread of nodal Na+ channels could contribute
significantly to temperature sensitivity and conduction block. During recovery
new clusters of Na+ channels were seen. In fibers with large-scale demyelination,
the new aggregates formed at the edges of adhering Schwann cells and appeared to
fuse to form new nodes. At nodes with demyelination limited to paranodal
retraction, Na+ channels were often found divided into two symmetric highly focal
clusters. These results suggest that reorganization of Na+ channels plays an
important role in the pathogenesis of demyelinating neuropathies.
PMID- 9655121
TI - Facilitation of human first dorsal interosseous muscle responses to transcranial
magnetic stimulation during voluntary contraction of the contralateral homonymous
muscle.
AB - The size of compound motor evoked potentials (cMEPs) to transcranial magnetic
stimulation of the motor cortex was measured in the relaxed first dorsal
interosseous muscle of the nondominant hand (ndFDI) during different levels of
voluntary contraction in the homonymous muscle of the dominant hand (dFDI). cMEP
responses in the ndFDI became larger when the dFDI was contracted to forces
ranging 10-70% of maximum voluntary contraction. Variability in the amplitude of
the cMEP responses in ndFDI decreased when dFDI was contracted. Comparison with
cMEPs to spinal cord stimulation suggested a large component of the facilitation
was occurring at a cortical level. The amplitude of cMEP responses in ndFDI also
increased when the tibialis anterior muscle of the leg on the contralateral side
was contracted. The observed facilitation of motoneurons during contraction of
contralateral muscles might involve a transcallosal pathway modulating the
excitability of one cortex when the other is activated.
PMID- 9655122
TI - The delayed depolarization in rat cutaneous afferent axons is reduced following
nerve transection and ligation, but not crush: implications for injury-induced
axonal Na+ channel reorganization.
AB - Two distinct populations of Na+ channels (kinetically fast and slow) are present
on the cell bodies and axons of cutaneous afferent neurons; the fast current is
increased and the slow current reduced in amplitude following nerve injury. The
present study was undertaken to determine if similar changes occur on the axons
of these neurons following peripheral nerve injury. The compound action
potentials from rat sural nerves were recorded in a sucrose gap chamber.
Following application of 4-aminopyridine, a prominent and well-characterized
depolarization (the delayed depolarization) followed the action potential. This
potential, only present on cutaneous afferent axons, has been correlated with
activation of a slow Na+ current. The delayed depolarization was reduced after
nerve transection. The refractory period of transmission of the action potential
was shortened in the transected nerves, but that of the delayed depolarization
was prolonged. The changes were largest when the sural nerve was cut and ligated
[control: 38.1 +/- 1.7% (n = 5); injury: 24.5 +/- 2.8% (n = 5), P < 0.05], which
prevented reconnection to its peripheral target. When the nerve was crushed and
allowed to reestablish peripheral target connections, the delayed depolarization
was minimally effected. These results indicate that the changes in Na+ channel
organization following peripheral target disconnection observed on cutaneous
afferent cell bodies also occur on their axons.
PMID- 9655123
TI - Functional magnetic stimulation of the respiratory muscles in dogs.
AB - This study assessed the ability of functional magnetic stimulation (FMS) to
activate the respiratory muscles in dogs. With the animal supine, FMS of the
phrenic nerves using a high-speed magnetic stimulator was performed by placing a
round magnetic coil (MC) at the carotid triangle. Following hyperventilation
induced apnea, changes in volume (deltaV) and airway pressure (deltaP) against an
occluded airway were determined. FMS of the phrenic nerves produced substantial
inspired function (deltaV = 373 +/- 20.5 mL and deltaP = -20 +/- 2.0 cm H2O).
After bilateral phrenectomies, maximal inspired deltaV (219 +/- 12.2 mL) and
deltaP (-10 +/- 1.0 cm H2O) were produced when the MC was placed near the C6-C7
spinous processes, while maximal expired deltaV (-199 +/- 22.5 mL) and deltaP (11
+/- 2.3 cm H2O) were produced following stimulation near the T9-T10 spinous
processes. We conclude: (1) FMS of either the phrenic or upper intercostal nerves
results in inspired volume production; (2) FMS of the lower intercostal nerves
generates expired volume production; and (3) FMS of the respiratory muscles may
be a useful noninvasive tool for artificial ventilation and assisted cough in
patients with spinal cord injuries or other neurological disorders.
PMID- 9655124
TI - Polyneural innervation in the psoas muscle of the developing rat.
AB - Polyneural innervation was studied in the psoas muscle in developing rats from P4
till P25 and at adult age, with the combined silver-acetylcholinesterase
technique. Nerve endings were counted, and end-plates were measured. These data
were compared with such data in the human. The end of polyneural innervation in
the rat (around P20) and in the human (around 12 weeks postterm age) in both
cases coincides with a transformation in motor behavior and postural control. The
rat's psoas muscle at early stages is less heavily innervated than this muscle in
the human. Up to three axons per motor end-plate were counted at P4, but in the
human up to five axons at 25 weeks of post menstrual age. This difference might
be related to the lower percentage of type I muscle fibers in the rat.
PMID- 9655125
TI - Myoglobin as a polymerase chain reaction (PCR) inhibitor: a limitation for PCR
from skeletal muscle tissue avoided by the use of Thermus thermophilus
polymerase.
AB - Skeletal muscle tissue contains polymerase chain reaction (PCR) inhibitors that
are coextracted by conventional nucleic acid extraction procedures. Myoglobin, a
heme-containing molecule, was shown to act as a potent Thermus aquaticus DNA
polymerase inhibitor and is likely to be involved in muscle tissue-associated PCR
inhibition. The use of Thermus thermophilus DNA polymerase avoids muscle tissue
associated PCR inhibition, and should be used in case of small amounts or
instability of the targeted nucleic acid.
PMID- 9655126
TI - Walking and fatigue in multiple sclerosis: the role of the corticospinal system.
AB - Transcranial magnetic stimulation was used to study motor evoked potentials
(MEPs) of leg muscles in controls and patients with multiple sclerosis (MS)
before and after walking. In controls, MEP areas were significantly reduced after
walking. A similar or greater reduction was seen in most patients, although there
was a wide range of values. The M waves were unchanged. We conclude that walking
induces functional changes of the corticospinal system and/or connected neurons
contributing to central fatigue, especially in patients with MS.
PMID- 9655127
TI - Macrophage apoptosis in muscle tissue in experimental autoimmune myasthenia
gravis.
AB - Combining in situ tailing and immunocytochemical staining, we demonstrated that
the infiltrating macrophages in muscle tissue sections during early phase of
experimental autoimmune myasthenia gravis (EAMG) in Lewis rats were eliminated by
apoptosis at high frequency. These apoptotic macrophages were colocalized in the
end-plate regions. Apoptosis is a major cause for elimination of infiltrating
macrophages during the early phase of EAMG.
PMID- 9655128
TI - The effect of age and temperature on mdx muscle fatigue.
AB - We have studied the in vitro contractile and fatigue characteristics of extensor
digitorum longus (EDL) muscles from 8- and 62-week-old dystrophin-deficient (mdx)
and control mice at 20 degrees C and 35 degrees C. There were no differences in
fatigability at 20 degrees C, but at 35 degrees C the dystrophin-deficient
muscles demonstrated increased fatigability compared to controls, with the older
mice exhibiting the greatest fatigue. These results suggest a temperature-related
mechanism of myofibrillar fatigue in dystrophin-deficient EDL muscles.
PMID- 9655129
TI - Pseudometabolic expression and phenotypic variability of calpain deficiency in
two siblings.
AB - Two siblings originating from Reunion Island were affected by a limb-girdle
muscular dystrophy (LGMD) type 2A and carried the same two mutations in the
calpain gene: 946-1 AG-->AA, affecting a splice site, and S744G. They
demonstrated the clinical variability possible with calpain-3 mutations. Onset
was around 20 years of age in each of them. The girl's symptoms mimicked a
metabolic myopathy, while her brother, at the same age, presented a classical
phenotype of LGMD in an advanced functional stage.
PMID- 9655130
TI - Diagnostic yield of stimulation and voluntary single-fiber electromyography in
myasthenia gravis.
AB - Voluntary and stimulation single-fiber electromyography were performed in the
extensor digitorum communis muscle of 15 myasthenic patients. The increase in
mean and individual mean consecutive difference as well as the proportion of
blocking in the volitional activation were greater than in the stimulation
method. These differences may be explained in part by the different degree of
alteration in large as compared with small motor units in patients with
myasthenia gravis.
PMID- 9655131
TI - Conduction block in vasculitic neuropathy.
AB - Vasculitis involving peripheral nerves usually presents as an acute asymmetrical
axonal neuropathy. We report a 67-year-old man with a symmetrical subacute
neuropathy in which nerve conduction studies showed prominent conduction block, a
finding indicative of demyelination. Sural nerve biopsy showed a vasculitic
neuropathy with invasion of blood vessel walls by inflammatory cells and a
mixture of nerve fiber loss and demyelination. The demyelination in this case was
presumably a consequence of subinfarctive nerve ischemia.
PMID- 9655132
TI - The effect of temperature on nerve conduction parameters in carpal tunnel
syndrome.
AB - Correction factors exist to allow for the dramatic effect that temperature has on
nerve conduction study parameters. However, these are based on normal nerves in
normal individuals and may not be appropriate in the diseased nerve setting. Our
clinical study showed that in carpal tunnel syndrome, the median nerve reacts
differently to temperature changes compared with normal ulnar controls.
Furthermore, statistically significant differences exist between the rates of
change with increasing temperature in motor and sensory nerves.
PMID- 9655133
TI - Sports and peripheral nerve injuries: report of 190 injuries evaluated in a
single electromyography laboratory.
AB - We retrospectively reviewed electrodiagnostic studies performed on 169 athletes
with 190 sports injuries to nerve fibers. Eighty-eight percent of the injuries
were to the upper extremity. Athletes participated in 27 sports, but over one
third of injuries were sustained playing football. The most common injuries were
burners (n = 38) and cervical radiculopathies (n = 18), followed by median (n =
28), axillary (n = 22), ulnar (n = 19), suprascapular (n = 14), and peroneal (n =
11) mononeuropathies. This is the largest reported series of sports-related nerve
injuries.
PMID- 9655134
TI - Lack of association between outcome measures of nerve regeneration.
AB - Studies of nerve regeneration in rodents utilize at least one of three classes of
outcome measures: electrophysiology, morphometry, and functional tests. The
assumption that these measures are correlated was tested utilizing a data set of
16 variables. Significant correlations (Spearman's rho, P < or = 0.05) were found
within variable classes; however, none were found between classes. The three
commonly utilized outcome measures do not measure the same phenomenon but rather
discrete aspects of nerve regeneration.
PMID- 9655135
TI - The contemporary role of F-wave studies. F-wave studies: clinical utility.
PMID- 9655136
TI - The contemporary role of F-wave studies. F-wave studies: limitations.
PMID- 9655137
TI - Bilateral femoral neuropathy during pregnancy.
PMID- 9655138
TI - Acute isolated ophthalmoplegia as a variant of Miller-Fisher syndrome.
PMID- 9655139
TI - Single-fiber electromyography improvement with 3,4-diaminopyridine in Lambert
Eaton myasthenic syndrome.
PMID- 9655140
TI - Significance of facial and trigeminal nerve involvement in Charcot-Marie-Tooth
disease type 1A: a case report.
PMID- 9655141
TI - Cerebral edema, cell volume regulation, and the role of ion channels in organic
osmolyte transport.
PMID- 9655142
TI - Identification of the volume-sensitive organic osmolyte/anion channel in human
glial cells.
AB - Cellular use of small organic solutes known as organic osmolytes for regulation
of the volume of the cell is a universal biological phenomenon. During swelling,
cells open an anion channel which allows for efflux of these solutes. This
channel is known as the volume-sensitive organic osmolyte/anion channel (VSOAC).
Anion channels with properties identical to VSOAC were found in human brain cells
obtained following pediatric neurosurgical procedures. The tissues examined
included tumors as well as putatively normal gray and white matter astrocytes.
The cells activated an anion conductance when swollen by hypotonic shock.
Baseline currents in these cells were generally small and increased up to 30-fold
within 10 min following the onset of swelling. The anion channel activated by
swelling was outwardly rectified and inactivated by depolarization, both
characteristic of the VSOAC. These observations indicate that human glial cells
and tumor cells activate VSOAC following cellular swelling. This suggests that
organic osmolyte efflux can be modulated during brain swelling by pharmaceuticals
which modulate VSOAC.
PMID- 9655143
TI - Endoscopic washout: a new technique for treating chronic subdural hematomas in
infants.
AB - Chronic hematomas are a common problem during infancy and usually occur as the
consequence of trauma. They tend to enlarge and are often managed successfully
with repeated subdural taps. In patients with collections that fail to respond to
percutaneous drainage, the choice of operative management, including burr hole
evacuation, shunting, or craniotomy, remains controversial. A new technique,
called endoscopic washout, was successfully used in 7 children under the age of 2
years who presented with irritability, vomiting, seizures, and rapid head growth.
Preoperative computerized tomography (CT) scans demonstrated enlarging,
bilateral, chronic subdural collections; these failed to respond to repeated
percutaneous taps over 10 days. With the patient positioned supine, bilateral
linear incisions were made anterior to the coronal suture in the midpupillary
lines and burr holes were placed. After the dura and outer membrane were opened
and coagulated with bipolar cautery, a 4-mm steerable fiberscope was introduced
into the subdural space to visualize the collections, evacuate any residual clot,
and continuously irrigate the space with lactated Ringer's solution warmed to
physiologic temperature. No bridging vessels or synechiae were violated; nitrous
oxide and hyperventilation were discontinued before removing the fiberscope. The
subdural space was irrigated again prior to closure. At follow-up (range 18
months to 8 years), CT scans showed reexpansion of the brain and no
reaccumulation of the hematomas. We conclude that the endoscopic washout is a
safe, uncomplicated treatment for chronic subdural hematomas in infants; is more
effective than treatment with conventional burr holes alone, and eliminates the
need for shunting or craniotomy.
PMID- 9655144
TI - Neoadjuvant chemotherapy for hypervascular malignant brain tumors of childhood.
AB - Some large hypervascular brain tumors pose an exceptional challenge to surgical
resection, particularly in young children with small blood volumes. To limit
blood loss during resection of hypervascular tumors, the authors used upfront
chemotherapy as the primary treatment modality in 2 young children. This produced
a dramatic reduction in tumor size and vascularity and greatly facilitated
definitive surgical removal.
PMID- 9655145
TI - Three-dimensional reconstruction and surgical navigation in pediatric epilepsy
surgery.
AB - We have used MRI-based three-dimensional (3D) reconstruction and a real-time,
frameless, stereotactic navigation device to facilitate the removal of seizure
foci in children suffering from intractable epilepsy. Using this system, the
location of subdural grid and strip electrodes is recorded on the 3D model to
facilitate focus localization and resection. Ten operations were performed,
including 2 girls and 8 boys ranging in age from 3 to 17, during which 3D
reconstruction and surgical instrument tracking navigation was used. In all the
cases, the patients tolerated the procedure well and showed no postoperative
neurological deficits. We believe this to be a valuable tool for a complete and
safe resection of seizure foci, thereby reducing the incidence of postoperative
neurological deficits and significantly improving the overall quality of life of
the patients.
PMID- 9655146
TI - On the surgical treatment of refractory epilepsy in tuberous sclerosis complex.
AB - The role of surgery in the treatment of refractory epilepsy (RE) in tuberous
sclerosis complex (TSC) is poorly defined. Four patients with RE and TSC were
evaluated for epilepsy surgery from 1994 to 1996. Three of four patients
developed infantile spasms within 5 months of birth. These progressed to frequent
complex partial and generalized tonic/myoclonic seizures refractory to
antiepileptic drug therapy. Neuroimaging revealed typical findings of TSC
including calcified lesions consistent with hamartomas. Clinical and EEG evidence
suggested an epileptic focus near a prominent lesion in each child. This was
confirmed using magnetic source imaging in 1 case. All patients underwent
inpatient continuous video-EEG monitoring followed by temporal lobectomy or focal
cortical resection with intraoperative EEG. Age at operation ranged from 5 to 13
years. Three out of 4 patients experienced a greater than 90% decrease in seizure
activity. One patient continues to have rare complex partial seizures, and 1 has
rare simple partial seizures. Tumor DNA analysis revealed mutations in the TSC1
gene in case 1 and the TSC2 gene in case 2; no mutations have been identified yet
in cases 3 and 4. Temporal lobectomy and focal cortical resection can result in
improved seizure control in patients with TSC and RE.
PMID- 9655147
TI - ISG viewing wand-guided endoscopic catheter placement for treatment of posterior
fossa CSF collections.
AB - Six patients presented with either entrapped fourth ventricles or
noncommunicating cerebrospinal fluid collections of the posterior fossa requiring
drainage. These collections were treated with shunt systems whose proximal
catheter was placed into the fourth ventricle via a coronal burr hole using an
endoscope guided by Eleckta's ISG Viewing Wand. The technique and its advantages
are described as are the complications and early outcomes.
PMID- 9655148
TI - Sinus pericranii: neuroradiologic findings and clinical management.
AB - We report an 11-year-old boy with a sinus pericranii. Magnetic resonance images
demonstrated a small hole in the cranium underneath the subcutaneous mass.
Magnetic resonance angiography (MRA) with sequential two-dimensional time-of
flight (2D-TOF) method demonstrated that the venous flow via the sinus pericranii
was directed from the intra- to the extracranial venous system (the drainer
type). This was confirmed by a combination of conventional cerebral angiography
and percutaneous sinography. We advocate that both the correct diagnosis and
classification of sinus pericranii can be established with a combination of
current noninvasive neuroradiologic studies, especially for the pediatric age
group. MRA with the 2D-TOF method is useful in the assessment of this venous
anomaly.
PMID- 9655149
TI - Beta-blockers and ultrafiltration failure.
PMID- 9655150
TI - Creatinine clearance and urea clearance in peritoneal dialysis: what to do in
case of discrepancy.
PMID- 9655151
TI - The role of Na,K-ATPase inhibitors in hypertension and end-stage renal disease.
AB - OBJECTIVE: To review the role of Na,K-ATPase inhibitors in the pathogenesis of
essential hypertension and hypertension associated with end-stage renal disease.
DATA SOURCES: MEDLINE search, 1966 to 1997. RESULTS: There is a suggestive
physiologic and epidemiologic relationship between Na,K-ATPase inhibition and
hypertension. However, clearance data cannot support the hypothesis that
differential metabolism of this family of compounds explains the improved
hypertensive control seen in patients on peritoneal dialysis compared to those on
hemodialysis. CONCLUSIONS: As a result of the complex methodologies involved, it
is unclear whether Na,K-ATPase inhibitors play a significant role in the
hypertension of end-stage renal disease in general and peritoneal dialysis in
particular.
PMID- 9655152
TI - Beta-blockers may cause ultrafiltration failure in peritoneal dialysis patients.
AB - OBJECTIVE: To elucidate mechanisms of ultrafiltration failure (UFF) in patients
on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective
analysis of patients with UFF during CAPD compared with cross-sectionally
selected controls. SETTING: University peritoneal dialysis center. PATIENTS:
Thirteen patients with UFF during CAPD necessitating change to hemodialysis (n =
6) or continuous cycling peritoneal dialysis (n = 1), or causing greatly
increased need for high glucose-containing solutes, were compared with 18 CAPD
patients without such problems. STATISTICS: Fisher's exact test, Student's
independent t-test, univariate and multivariate correlation analyses. MAIN
OUTCOME MEASURES: Data were collected prior to analyses. RESULTS: Systolic blood
pressure and total cholesterol and triglyceride levels were higher in the UFF
patients than in the controls (p = 0.006, p = 0.028, p = 0.013). Beta-blockers
were used by 12 of the UFF patients, but only 2/ 18 controls (p < 0.0001). There
was no intergroup difference in number of women, patient age or weight, incidence
of diabetes or previous peritonitis, duration of PD, serum levels of albumin,
creatinine, iron, or ferritin, or dosage of erythropoietin. Correlation was found
between the daily amount of glucose instilled into the abdomen and serum
triglycerides (r = +0.72, p < 0.001), total cholesterol (r = +0.56, p = 0.008),
and HbA1C (r =-0.41, p = 0.039). Many patients were high absorbers of dialysis
glucose. CONCLUSION: The study indicates that beta-blockers may cause UFF, and
that glucose and lipid metabolism differed between these patients and controls
without UFF.
PMID- 9655153
TI - Effect of bicarbonate-based dialysis solutions on intracellular pH (pHi) and
TNFalpha production by peritoneal macrophages.
AB - OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate
based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha
(TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi).
DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates
collected after overnight dwells in peritonitis-free continuous ambulatory
peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25%
dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate
buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained
lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg,
respectively. In all experiments pCO2 was carefully maintained at a stable level.
The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to
different dialysis solutions or Hank's balanced salt solution. TNFalpha levels
were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated
PMphi after their incubation in different solutions for 15 and 30 minutes.
TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT
PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in
different solutions for 30 minutes. beta-actin mRNA was used as the control.
RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial
drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation
in TB and TBL, respectively. In comparison to the control solution, a fall of 11%
and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30
minutes, respectively, and 15% and 26% after incubation in TBL. Under identical
conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95%
suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was
severely depressed by Dianeal but no detectable inhibition was observed following
incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and
TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not
suppressed by more than 49%, even after 30 minutes incubation. Moreover,
suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at
high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both
bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate
this effect to be responsible for the improved capacity of PMphi to secrete
TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal.
Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the
protective effect of TB and TBL on immune function of PMphi. TBL is as effective
as TB in preventing the deleterious effect of Dianeal on PMphi function.
PMID- 9655154
TI - Calcium concentration in the CAPD dialysate: what is optimal and is there a need
to individualize?
AB - OBJECTIVE: To evaluate risk/benefit of various continuous ambulatory peritoneal
dialysis (CAPD) dialysate calcium concentrations. DATA SOURCES: A review of the
literature on the effects of various CAPD dialysate Ca concentrations on plasma
Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium
carbonate, doses of vitamin D analogs, and requirements of aluminum-containing
phosphate binders. STUDY SELECTION: Eleven studies of nonselected CAPD patients,
and 13 studies of CAPD patients with hypercalcemia were reviewed. RESULTS: In
nonselected CAPD patients, treatment with a reduced dialysate Ca concentration
(1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or
vitamin D metabolites and reduced the need for Al-containing phosphate binders.
When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca
and increase of PTH could easily be reversed with an immediate adjustment of the
treatment. After 3 months, stable plasma Ca and PTH levels could be maintained
using only monthly investigations. In patients with hypercalcemia and elevated
PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied
a considerable risk for the progression of secondary hyperparathyroidism. When
hypercalcemia was present in combination with suppressed PTH levels, a controlled
increase of PTH could be obtained with a temporary discontinuation of vitamin D
and/or a reduction of calcium carbonate treatment in combination with a dialysate
Ca concentration of 1.25 or 1.35 mmol/L. CONCLUSION: Most CAPD patients can be
treated effectively and safely with a reduced dialysate Ca concentration of 1.35
or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L
should not be used. A small fraction of patients with persistent hypocalcemia
need treatment with high dialysate Ca, such as 1.75 mmol/L.
PMID- 9655155
TI - Touch contamination of connection devices in peritoneal dialysis--a quantitative
microbiologic analysis.
AB - OBJECTIVE: To determine the level of bacterial contamination associated with
touch contact of a connector set during peritoneal dialysis (PD). DESIGN: The
experiment utilized a laboratory-based simulation of a bag exchange procedure.
Deliberate touch contamination of the connector set spike was followed by
quantitative recovery of micro-organisms from the connector and, in some cases,
the dialysis bag. SUBJECTS: Patients undergoing PD were used as the "test" group.
Departmental secretarial and laboratory staff served as the comparative control
group. SETTING: The patients were voluntary subjects from a PD outpatients unit
and were tested in their own homes. OUTCOME: The numbers of micro-organisms
contaminating a connector set and entering the dialysis bag during a touch
contamination event were determined. Additionally we identified hand hygiene and,
in particular, the care taken to dry the hands after washing as being highly
relevant to microbial touch-contamination levels. Patient hand disinfection, as
practised in most PD units, effectively reduced touch contamination to low
levels. RESULTS: Touch contamination of a connector set with unprepared hands led
to fewer than 100 micro-organisms translocating from fingers to the spike. If the
hands were washed but not dried before touch contact was made, up to 4500 micro
organisms translocated to the connector set spike. Air-towel drying of washed
hands before touch contact reduced the translocating numbers by 95%-99%. Hand
disinfection, as routinely practiced by PD patients, reduced the bacterial
numbers reaching the peritoneal cavity after touch contamination to <5. The range
of micro-organisms isolated from the fingers of PD patients using hand
disinfectants on a regular basis showed considerably more diversity than the
control group. CONCLUSION: Hand care prior to bag exchange has a major effect on
touch-contamination levels. Accidental touch contact of connecting devices by
unprepared hands using a PD-bag exchange procedure leads to the translocation of
500 micro-organisms or fewer to the connector device. If the hands are wet at the
time of contact the number translocating can be as high as 4500. Hand drying with
an air towel before touch contact reduces the numbers translocating by 95%-99%.
Hand disinfection procedures carried out prior to bag exchange minimizes touch
contamination levels.
PMID- 9655156
TI - Symptomatic ascites after discontinuation of continuous peritoneal dialysis.
AB - OBJECTIVE: To analyze pathogenetic associations, clinical features, management,
and outcome of ascites following discontinuation of continuous peritoneal
dialysis (CPD). DESIGN: Retrospective analysis of symptomatic ascites, defined as
ascites requiring at least one therapeutic paracentesis, developing in patients
who discontinued CPD. SETTING: Dialysis unit of one tertiary care center.
PARTICIPANTS: Twelve patients with 13 episodes of symptomatic ascites diagnosed
soon after (a few days to 2 months) discontinuation of CPD. INTERVENTIONS:
Diagnostic tests to characterize the pathogenesis of ascites; management of
ascites by hemodialysis or CPD. MAIN OUTCOME MEASURES: Evolution of clinical
features and nutritional parameters, survival. RESULTS: Ascites was infectious in
3 episodes (non-tuberculous mycobacterial peritonitis) and noninfectious in the
remaining 10 episodes. Serum-to-ascites albumin concentration gradient (AG) was
6.3 +/- 1.5 g/L in infectious ascites and 17.3 +/- 2.7 g/L ( >11 g/L in every
episode) in noninfectious ascites. Infectious ascites was managed with
hemodialysis, prolonged courses of antimicrobial agents, and repeated
paracentesis. Paracentesis ceased after 3-9 months. The patients were alive after
52 +/- 19 months. Seven episodes of noninfectious ascites were managed by
hemodialysis and repeated paracentesis. Five patients died within 6 months from
cardiac causes or sepsis. The remaining 2 patients died after 14 and 16 months
from cardiac causes. Three episodes of noninfectious ascites in 2 patients were
treated by restarting CPD within 2-5 months. Patients were alive at 16.9 +/- 13.2
months. They were asymptomatic and achieved fluid control. On the same CPD
schedule, peritoneal clearances of urea and creatinine and normalized protein
nitrogen appearance were unchanged between the initial and restarted CPD. Serum
albumin was 33.3 +/- 2.5 g/L at the end of the first CPD period, 23.6 +/- 2.5 g/L
soon after restarting CPD, and 31.3 +/- 5.5 g/L 4 months after restarting CPD.
CONCLUSIONS: Noninfectious ascites after discontinuation of CPD is often
characterized by an AG > 11 g/L, suggesting portal hypertension. Restarting CPD
in noninfectious ascites may be associated with improvement in ascites
symptomatology and nutritional parameters and with satisfactory survival.
PMID- 9655158
TI - Computerized kinetic modeling: a new tool in the quest for adequacy in peritoneal
dialysis.
AB - Until recently, kinetic modeling of peritoneal dialysis (PD) was performed by
engineers, scientists, or nephrologists at major teaching institutions. Now there
are several "user-friendly" computer programs which permit the practicing
nephrologist and dialysis staff to monitor adequacy of the individual PD patient
and to optimize the dialysis prescription. In this brief article, the
capabilities, methods, and data requirements of three programs are reviewed, and
specific recommendations for the selection of a particular program are discussed.
PMID- 9655157
TI - Peritoneal dialysis in children under 5 years of age.
AB - OBJECTIVE: We report our experience with maintenance peritoneal dialysis (PD) in
small children. DESIGN: This is a retrospective analysis of the patient records
of all children under the age of 5 years treated with continuous peritoneal
dialysis (CPD) between 1986 and 1994 in Finland. SETTING: Treatment was started
and the patients were seen at the outpatient clinic at the Hospital for Children
and Adolescents, University of Helsinki, every 3 months. Between these visits,
they had controls at their local hospital every 2-4 weeks. PATIENTS: The most
common primary renal disease in these 34 patients was congenital nephrotic
syndrome of the Finnish type (27 patients). Others were: congenital nephrotic
syndrome (3 patients), polycystic kidney disease (1), urethral valve (1),
neuroblastoma (1), and renal dysplasia (1). RESULTS: Mean age at onset was 1.6
years and median treatment time 9.3 months. Time spent in hospital decreased from
270 days/year in the 1980s to 150 days/year in the 1990s. Two children died
(5.9%). The peritonitis rate on continuous cyclic peritoneal dialysis was 1:11.5
patient-months. Hernias were diagnosed in 29% of the patients. After 3 months
half of the patients were on antihypertensive medication. Pulmonary edema was
diagnosed once in 12 patients and twice in 2 patients. During the first 6 months
on PD the mean height standard deviation score (hSDS) increased from -2.13 to
1.66 (p < 0.0001). The 6-month change in hSDS before initiation and 6 months
after the start of CPD increased from -0.12 +/-0.68 to +0.59 +/- 0.64 (p =
0.0008). CONCLUSIONS: Our results indicate that peritoneal dialysis is feasible
and safe in small children. Mortality was low and growth was good. The major
challenges presented by CPD therapy were maintenance of optimal nutrition,
avoidance of peritonitis, and control of volemia.
PMID- 9655159
TI - Abdominal catastrophe: visceral injury as a cause of peritonitis in patients
treated by peritoneal dialysis.
AB - OBJECTIVE: Peritonitis is considered an acceptable and controllable risk in
patients undergoing chronic peritoneal dialysis (PD). In contrast, peritonitis
due to visceral leakage represents a true "abdominal catastrophe" because of
striking morbidity and mortality. To delineate the incidence, causes, and
outcomes of catastrophic peritonitis, we compared patients who developed
peritonitis due to documented visceral leakage with patients who developed
peritonitis due to enteric organisms without evidence of visceral leakage.
DESIGN: Retrospective chart review. SETTING: PD Unit located in tertiary care
referral center. PATIENTS: 230 patients treated by PD between January 1988 and
June 1996. MAIN OUTCOME MEASURES: All episodes of PD-related peritonitis
occurring over an 8-year period. Hospital course of all patients with or without
renal failure who were treated at University Hospitals of Cleveland for ischemic
bowel disease, cholecystitis, viscus perforation, or diverticulitis. RESULTS:
Anatomically documented visceral injury caused 32.5% of episodes of enteric
bacterial peritonitis in 72 patients between January 1988 and June 1996. The
overall incidence of this "abdominal catastrophe" was 11.3%, or 26 of a total of
230 patients treated by PD. Of the 26 patients, 50% died, 30.7% survived but
switched permanently to hemodialysis, and only 19.2% remained on, or returned to,
PD. Compared to renal failure patients treated by hemodialysis or transplantation
and to non-renal failure patients, the incidence of abdominal catastrophe was 20
60 times greater in patients treated by PD. CONCLUSIONS: Evidence for injury of
an abdominal organ should be sought in all patients treated by PD who develop
peritonitis with enteric organisms. Surgical intervention is definitive for
diagnosis, and if performed early may reduce morbidity and mortality.
PMID- 9655160
TI - Increased endothelin-1 mRNA expression in peripheral blood monocytes of dialysis
patients.
AB - OBJECTIVE: To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in
peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous
ambulatory peritoneal dialysis (CAPD). DESIGN: Endothelin-1 mRNA level in
peripheral blood monocytes and plasma ET-1 level were studied in 30 HD patients,
15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20
normal healthy controls. Hemodialysis patients were dialyzed three times per week
with a bicarbonate dialysate. Different types of dialyzer membrane, viz.,
cellulose triacetate, cuprophane, polysulfone, polyacrylonitrile, and
ethylenevinylalcohol were used in 8, 6, 6, 5, and 5 patients, respectively.
Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily
exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to
2.5%. RESULTS: Higher levels of ET-1 mRNA in monocytes were observed in HD
patients than in CAPD patients (p < 0.01), chronic renal failure patients (p <
0.01), or normal healthy controls (p < 0.001). The level of ET-1 mRNA in
monocytes at the end of HD was not significantly higher than that at the start of
HD. In addition, these mRNA levels in HD patients showed little difference with
different types of dialysis membrane. Plasma ET-1 level in HD patients (10.2 +/-
2.4 pg/mL) was also higher than that in CAPD patients (7.8 +/- 1.6 pg/mL, p <
0.01), in chronic renal failure patients (4.8 +/- 1.2 pg/mL, p < 0.01), or in
normal controls (2.6 +/- 0.8 pg/mL, p < 0.001). CONCLUSION: Dialysis itself did
not significantly affect ET-1 mRNA levels in monocytes. Chronic stimulation of
peripheral blood monocytes may be associated with higher levels of ET-1 mRNA and
plasma ET-1 in HD patients than in CAPD patients.
PMID- 9655162
TI - Pasteurella multocida peritonitis in peritoneal dialysis patients: beware of the
cat.
PMID- 9655161
TI - Serum disaccharides and osmolality in CCPD patients using icodextrin or glucose
as daytime dwell.
AB - OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin-
and glucose-containing dialysis fluid during continuous cycling peritoneal
dialysis (CCPD), patients were treated for 2 years with either icodextrin- or
glucose-containing dialysis fluid for their daytime dwell (14-15 hours). Prior to
entry into the study, all patients used a standard glucose solution (Dianeal
1.36%, 2.27%, or 3.86%, Baxter, Utrecht, The Netherlands). DESIGN: Open,
randomized, prospective, two-center study. SETTING: University hospital and
teaching hospital. PATIENTS: Both established and patients new to CCPD were
included. A life expectancy of more than 2 years, a stable clinical condition,
and written informed consent were necessary before entry. Patients aged under 18,
those with peritonitis in the previous month, and women of childbearing
potential, unless taking adequate contraceptive precautions, were excluded.
Thirty-eight patients entered the study, and 25 (13 glucose, 12 icodextrin) had a
follow-up period of 12 months or longer in December 1996. MAIN OUTCOME MEASURES:
Serum icodextrin metabolites: one to five glucose units (G1-G5), a high molecular
weight fraction (G > 10), and total carbohydrate level, as well as a biochemical
profile were determined every 3 months in combination with all other study
variables. RESULTS: In icodextrin-treated patients, serum disaccharide (maltose)
concentrations increased from 0.05 +/- 0.01 (mean +/- SEM) at baseline, to an
average concentration in the follow-up visits of 1.14 +/- 0.13 mg/mL (p < 0.001).
All icodextrin metabolites increased significantly from baseline, as illustrated
by the serum total carbohydrate minus glucose levels: from 0.42 +/- 0.05 mg/mL to
an average concentration in the follow-up visits of 5.04 +/- 0.49 mg/mL (p <
0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L
to an average concentration in the follow-up visits of 135.4 +/- 0.8 mmol/L (p <
0.05). However, after 12 months the serum sodium concentration increased
nonsignificantly (NS) from baseline to 136.6 +/- 0.9 mmol/L, after an initial
decrease. Serum osmolality increased significantly from baseline in icodextrin
users at 9 and 12 months, but did not differ significantly from glucose users in
any visit. In icodextrin-treated patients, the calculated serum osmolal gap
increased significantly from 4.1 +/- 1.4 mOsm/kg to an average of 11.8 +/- 1.7
mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in
millimoles/liter equaled the increase in osmolal gap. Body weight increased in
icodextrin users (71.9 +/- 2.8 kg to 77.8 +/- 3.0 kg; NS). Clinical adverse
effects did not accompany these findings. Residual renal function remained stable
during follow-up. CONCLUSIONS: The serum icodextrin metabolite levels in the
present study increased markedly and were the same as those found previously in
continuous ambulatory peritoneal dialysis patients treated with icodextrin,
despite the longer dwell time for CCPD patients (14-16 hr versus 8-12 hr). The
initial decrease in serum sodium concentration was followed by an increase to a
concentration not different from baseline at 12 months. The pathophysiology of
this finding is speculated. Calculated osmolal gap in icodextrin patients
increased significantly (p < 0.01) at every follow-up visit, and could be
explained by the serum icodextrin metabolite increase. We encountered no clinical
side effects of the observed levels of icodextrin metabolites.
PMID- 9655164
TI - No risk for peritonitis by sampling with a modified PET.
PMID- 9655163
TI - A simplified laparoscopic salvage technique for malfunctioning chronic peritoneal
dialysis catheters.
PMID- 9655165
TI - Brevibacterium iodinum peritonitis associated with acute urticaria in a CAPD
patient.
PMID- 9655166
TI - Chronic administration of iron dextran into the peritoneal cavity of rats.
PMID- 9655167
TI - Potential problem: delayed detection of peritonitis by patients receiving home
automated peritoneal dialysis (APD)
PMID- 9655168
TI - Vancomycin-resistant enterococci and empirical vancomycin for CAPD peritonitis.
PMID- 9655169
TI - Monoarthritis in a patient with lupus nephritis on peritoneal dialysis.
PMID- 9655170
TI - Peritoneal dialysis case forum. Was CAPD the answer to this patient's complex
problems?
PMID- 9655171
TI - Literature. November-December 1997.
PMID- 9655172
TI - Nursing application: Handwashing and other gripping nursing issues.
PMID- 9655173
TI - Expression and localization of insulin-like growth factor-1 in normal and post
burn hypertrophic scar tissue in human.
AB - The migration of epithelial cells from dermal appendages toward the wound surface
is essential for re-epithelialization of partial thickness burn injuries. This
study provides evidence that these cells in vivo synthesize a mitogenic and
fibrogenic factor, insulin-like growth factor-1 (IGF-1), which may promote the
development of the post-burn fibroproliferative disorder, hypertrophic scarring
(HSc). An evaluation of 7 post-burn hypertrophic scars, 7 normal skin samples
obtained from the same patients and 4 mature scars revealed that IGF-1 expressing
cells from the disrupted sweat glands tend to reform small sweat glands of 4-10
cells/gland in post-burn HSc. The number of these cells increases with time and
the glands become larger in mature scar. Other epithelial cells such as those
found in sebaceous glands and basal and suprabasal keratinocytes, also express
IGF-1 protein and mRNA as detected by Northern and RT-PCR analysis of RNA
obtained from whole skin and separated epidermis and dermis. However, cultured
keratinocytes did not express mRNA for IGF-1. Histological comparisons between
normal and HSc sections show no mature sebaceous glands in dermal fibrotic
tissues but the number of IGF-1 producing cells including infiltrated immune
cells was markedly higher in the dermis of hypertrophic scar tissues relative to
that of the normal control. In these tissues, but not in normal dermis, IGF-1
protein was found associated with the extracellular matrix. By in situ
hybridization, IGF-1 mRNA was localized to both epithelial and infiltrated immune
cells. Collectively, these findings suggest that in normal skin, fibroblasts have
little or no access to diffusible IGF-1 expressed by epithelial cells of the
epidermis, sweat and sebaceous glands; while following dermal injury when these
structures are disrupted, IGF-1 may contribute to the development of fibrosis
through its fibrogenic and mitogenic functions. Reformation of sweat glands
during the later stages of healing may, therefore, limit this accessibility, and
lead to scar maturation.
PMID- 9655174
TI - Inhibition of DNA topoisomerase I activity by heparan sulfate and modulation by
basic fibroblast growth factor.
AB - Eukaryotic DNA topoisomerase I catalyzes changes in the superhelical state of
duplex DNA by transiently breaking single strands thereby allowing relaxation of
both positively and negatively supercoiled DNA. Topoisomerase I is a nuclear
enzyme localized at active sites of transcription, and abnormal levels of the
enzyme have been observed in a variety of neoplasms. Because the enzyme binds
heparin and, given the presence of heparan sulfate within the nuclei of mammalian
cells, we sought to investigate the interaction between topoisomerase I and
sulfated glycosaminoglycans isolated from normal and neoplastic human liver. The
results demonstrated that low concentrations (approximately 100 nM) of heparan
sulfate from normal liver but not from its malignant counterpart effectively
blocked relaxation of supercoiled DNA driven by either purified holoenzyme or
topoisomerase I activity present in nuclear extracts of three malignant cell
lines. Heparin acted at even lower (approximately 10 nM) concentrations.
Moreover, we show that basic fibroblast growth factor could interfere with this
heparan sulfate/heparin-driven inhibition and that both basic fibroblast growth
factor and heparin-binding sites co-localized in the nuclei of U937 leukemic
cells. Our results suggest that DNA topoisomerase I activity may be modulated in
vivo by specific heparan sulfate moieties present in normal cells but markedly
reduced or absent in their transformed counterparts.
PMID- 9655175
TI - Inhibition of neuronal nitric oxide synthase (n-cNOS) reverses the corticotrophin
induced behavioral effects in rats.
AB - The nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (N-NMMA) and
the competitive substrate for NO synthase L-arginine were used to determine the
role of endogenous NO on the behavioral and neuroendocrine responsiveness
following systemic corticotrophin in dexamethasone-suppressed rats.
Corticotrophin (50-200 mU/kg, s.c.) dose-dependently decreased behavioral
activity in the actimeter and produced significant anxiolytic and anti-risk
activity in the plus-maze behavior test, without affecting systolic blood
pressure. Rats given corticotrophin showed significant increased plasma
corticosterone and reduced adrenal ascorbic acid level. These behavioral and
adrenal responses of corticotrophin were dose dependently blocked by metyrapone
(20 and 50 mg/kg, i.p.), an inhibitor of steroid 11beta-hydroxylase in adrenal
and neural tissues that block steroidogenesis. Intracerebroventricular
administration of L-NMMA (20 microg/rat in 10 microl) significantly prevented the
behavioral hypoactivity and anxiolytic-like responses of corticotrophin without
influencing the adrenal responsiveness. The effect of L-NMMA was completely
reversed by preadministration of L-arginine (300 mg/kg, i.p.). These results
suggest that neuronal nitric oxide pathway plays an important modulating role in
the behavioral effects of corticotrophin by mechanisms other than those involving
cardiovascular effects.
PMID- 9655176
TI - Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+
channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin
sensitive G-protein.
AB - In single rabbit aortic smooth muscle cells, and at a concentration known to
induce a maximum sustained increase of intracellular Ca2+ via activation of the
steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10(-7) M) and
insulin (80 microU/ml) were found to induce a sustained increase in cytosolic
free Ca2+ ([Ca]i) levels that was significantly attenuated by pre-treatment with
either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular
Ca2+. However, both PTX and CTX failed to inhibit the sustained depolarization
evoked sustained Ca2+ influx and [Ca]i elevation via activation of the R-type
Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+
influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide
(BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were
completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110
(isradipine). These data suggest that both insulin and ET-1 activate the
nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R
type Ca2+ channels present on rabbit VSMCs and these channels are directly
coupled to PTX and CTX sensitive G protein(s).
PMID- 9655177
TI - Ascorbate-Fe2+ lipid-peroxidation of rat liver microsomes: effect of vitamin E
and cytosolic proteins.
AB - In the present study, we examined the effect of the intraperitoneal
administration of vitamin E (100 mg/kg weight/24 h) on ascorbate (0.4 mM) induced
lipid peroxidation of rat liver microsomes . We also analyzed the effect of
hepatic cytosolic proteins on this process. The results indicate that the
ascorbate induced light emission was 76% lower in microsomes (1 mg protein)
obtained from vitamin E treated animals when compared with controls. In the
presence of cytosolic protein (1 mg) the chemiluminescence of control microsomes
diminished 55.8 and 59.5% when cytosol from controls and treated animals was
used, respectively. The chemiluminescence of vitamin E microsomes diminished
25.03 and 22.08% when both types of cytosol were added to the medium. Dialyzed or
treated at 70 degrees C cytosol was also able to inhibit the lipid peroxidation
of either control or vitamin E rat liver microsomes. By means of gas
chromatography we analyzed the fatty acid composition of native and peroxidated
microsomes from both animal groups. The peroxidation affected principally
arachidonic acid and its diminution was more evident in the control microsomes
than in the microsomes from the vitamin E treated group. By HPLC we analyzed the
vitamin E content in all subcellular fractions employed. In microsomes from the
vitamin E-group, the content of vitamin was 11 times higher than in the control
ones (0.678 +/- 0.1038 vs. 0.062 +/- 0.0045 microg alpha-tocopherol/mg protein,
respectively), while levels in the cytosol from the vitamin E-group were only 2
times higher than in the control cytosol (0.057 +/- 0.0051 vs. 0.025 +/- 0.0015
microg alpha-tocopherol/mg protein, respectively).
PMID- 9655178
TI - Association of myeloperoxidase with heparin: oxidative inactivation of proteins
on the surface of endothelial cells by the bound enzyme.
AB - Chromatography of human myeloperoxidase (MPO) on a heparin-agarose column
demonstrated a tight association of the protein with the resin. The
electrophoretic mobility of mixtures of MPO and heparin in polyacrylamide gels
under nondenaturing conditions was consistent with a strong interaction of the
cationic enzyme with the polyanionic polysaccharide. Purified MPO prebound to
bovine aorta endothelial cells (BAEC) and supplemented with hydrogen peroxide
dose- and time-dependently abrogated the interaction of coagulation factor IX
(FIX) with factor IX-binding protein (FIXBP) on the surface of BAEC reflecting
oxidative modification of the binding protein. This inactivation of FIXBP
required the presence of chloride implicating hypochlorite in the reaction.
Hypochlorite and activated neutrophils exerted a similar effect. The oxidative
modification of FIXBP was only partially dependent on the addition of hydrogen
peroxide and was abolished by exogenous heparin which displaced MPO from the cell
surface, emphasizing the functional differences between cell-bound and free
enzyme.
PMID- 9655179
TI - Possible mechanism of captopril induced endothelium-dependent relaxation in
isolated rabbit aorta.
AB - The mechanism of captopril, an angiotensin converting enzyme (ACE) inhibitor with
sulfhydryl group (SH) in its structure, to produce an endothelium-dependent
vasorelaxation was studied. In rabbit aorta with intact endothelium and
precontracted with phenylephrine, captopril and superoxide dismutase (SOD)
produced dose-dependent relaxation. Lisinopril, an ACE inhibitor without a -SH
group in its structure, did not produce endothelium-dependent relaxation. It was
observed that captopril, like SOD, produced the relaxation by protecting the EDRF
from getting inactivated by superoxide anions as pyrogallol and methylene blue
inhibited both the captopril and SOD-mediated relaxation. The free radical
scavenging action of captopril is further substantiated by the observation that
captopril, but not lisinopril, inhibited FeCl3/ascorbic acid-induced lipid
peroxidation in whole tissue homogenates of rabbit aorta to a level comparable to
that of SOD. These results suggest that endothelium-dependent vasodilation
produced by captopril may be due to its ability to scavenge superoxide anion and
this property may be ascribed to the -SH group present in its structure.
PMID- 9655180
TI - An alpha subunit-deficient form of eukaryotic protein synthesis initiation factor
eIF-2 from rabbit reticulocyte lysate and its activity in ternary complex
formation.
AB - Eukaryotic protein synthesis initiation factor eIF-2 is usually isolated as a
heterotrimer (alphabeta gamma). By use of Sephacryl S-300 fractionation an alpha
subunit-deficient form of eIF-2 was identified in impure preparations from rabbit
reticulocyte lysate and it appeared in these preparations to be still active in
formation of the ternary complex (eIF-2.GTP.Met-tRNAi). Subsequently alpha
subunit-deficient eIF-2 was further purified and this appeared to have retained
ternary complex forming activity. Together with a suggested lack of involvement
of the beta subunit this implies that the alpha subunit was not required for
activity and the gamma subunit bound both GTP and Met-tRNAi in formation of the
ternary complex. The identification and study of alpha subunit-deficient eIF-2
thus elucidated the involvement of the subunits in binding of GTP and Met-tRNAi
to produce the ternary complex in polypeptide chain initiation.
PMID- 9655181
TI - Hyperosmolality-induced abnormal patterns of calcium mobilization in smooth
muscle cells from non-diabetic and diabetic rats.
AB - Hyperglycemia and/or hyperosmolality may disturb calcium homeostasis in vascular
smooth muscle cells (SMCs), leading to altered vascular contractility in
diabetes. To test this hypothesis, the KCl-induced increases in [Ca2+]i in
primarily cultured vascular SMCs exposed to different concentrations of glucose
were examined. With glucose concentration in solutions kept at 5.5 mM, KCl
induced a fast increase in [Ca2+]i which then slowly declined (type 1 response)
in 83% of SMCs from non-diabetic rats. In 9% of non-diabetic SMCs KCl induced a
slow increase in [Ca2+]i (type 2 response). Interestingly, under the same culture
conditions KCl induced type 1 and type 2 responses in 47 and 35% of SMCs from
diabetic rats. When SMCs from non-diabetic or diabetic rats were cultured in 36
mM glucose, KCl induced a fast increase in [Ca2+]i which, however, maintained at
a high level (type 3 response). The sustained level of [Ca2+]i in the presence of
KCl was significantly higher in cells cultured with 36 mM glucose than that in
non-diabetic cells cultured with 5.5 mM glucose. Furthermore, the hyperglycemia
induced alterations in calcium mobilization were similarly observed in cells
cultured in high concentration of mannitol (30.5 mM) or L-glucose, indicating
that hyperosmolality was mainly responsible for the abnormal calcium mobilization
in diabetic SMCs.
PMID- 9655182
TI - Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the
dystrophin-deficient mdx mouse.
AB - The mdx mouse, an animal model of the Duchenne muscular dystrophy, was used for
the investigation of changes in mitochondrial function associated with dystrophin
deficiency. Enzymatic analysis of skeletal muscle showed an approximately 50%
decrease in the activity of all respiratory chain-linked enzymes in musculus
quadriceps of adult mdx mice as compared with controls, while in cardiac muscle
no difference was observed. The activities of cytosolic and mitochondrial matrix
enzymes were not significantly different from the control values in both cardiac
and skeletal muscles. In saponin-permeabilized skeletal muscle fibers of mdx mice
the maximal rates of mitochondrial respiration were about two times lower than
those of controls. These changes were also demonstrated on the level of isolated
mitochondria. Mdx muscle mitochondria had only 60% of maximal respiration
activities of control mice skeletal muscle mitochondria and contained only about
60% of hemoproteins of mitochondrial inner membrane. Similar findings were
observed in a skeletal muscle biopsy of a Duchenne muscular dystrophy patient.
These data strongly suggest that a specific decrease in the amount of all
mitochondrial inner membrane enzymes, most probably as result of Ca2+ overload of
muscle fibers, is the reason for the bioenergetic deficits in dystrophin
deficient skeletal muscle.
PMID- 9655183
TI - The mitogen-activated protein kinase pathway contributes to vanadate toxicity in
vascular smooth muscle cells.
AB - Vanadate has been considered in the treatment of diabetes because of its insulin
like effects. However, it has severe toxic effects in both animal and man. In
cultured cells, vanadate can either cause death or be growth stimulatory,
depending on the cell type and growth conditions. Here, we report that in baboon
aortic smooth muscle cells (SMCs), vanadate induced p42/p44 mitogen-activated
protein kinase (MAPK) activity. This effect was abolished in the presence of the
specific MAPK kinase (MAPKK) inhibitor PD098059. Although activation of
p42/p44MAPK/MAPKK is generally thought to be necessary for proliferation, in
SMCs, vanadate did not promote DNA synthesis and inhibited thymidine
incorporation stimulated by platelet-derived growth factor (PDGF)-BB in a dose
dependent fashion (IC50: 30 microM). Prolonged exposure to vanadate exerted
cytotoxic effects. Cells retracted, rounded up and detached from the substratum.
These vanadate-induced morphological changes were blocked in the presence of
PD098059. The addition of PDGF-BB further activated p42/p44MAPK/MAPKK in the
presence of vanadate and substantially increased vanadate toxicity. We conclude
from these observations that activation of the p42/p44MAPK/MAPKK signalling
module contributes to the cytotoxic effects induced by vanadate.
PMID- 9655184
TI - DNA sequence and muscle-specific expression of human sarcosin transcripts.
AB - We have characterized two abundant human cDNAs which, through Northern
hybridization analysis, are selectively expressed in human sarcomeric muscle. DNA
sequencing was performed and the two cDNAs were found to share sequence identity,
with the exception of a 3' UTR extension present on the longer transcript. Our
data suggest that the two transcripts are generated through alternative use of
two poly(A) addition signals. The cDNAs encode a large open reading frame
encompassing at least 435 codons. Through sequence comparisons, both at the DNA
and predicted amino acid sequence level, we have been unable to find significant
sequence similarity to any other characterized sequence. Consequently, we have
termed this novel human sequence sarcosin. Although novel, Southern hybridization
analysis demonstrated that the sarcosin sequence has been conserved in several
mammalian species.
PMID- 9655185
TI - Tyrosine kinases and calcium dependent activation of endothelial cell
phospholipase D by diperoxovanadate.
AB - Reactive oxygen species (ROS) mediated modulation of signal transduction pathways
represent an important mechanism of cell injury and barrier dysfunction leading
to the development of vascular disorders. Towards understanding the role of ROS
in vascular dysfunction, we investigated the effect of diperoxovanadate (DPV),
derived from mixing hydrogen peroxide and vanadate, on the activation of
phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAECs).
Addition of DPV to BPAECs in the presence of .05% butanol resulted in an
accumulation of [32P] phosphatidylbutanol (PBt) in a dose- and time-dependent
manner. DPV also caused an increase in tyrosine phosphorylation of several
protein bands (Mr 20-200 kD), as determined by Western blot analysis with
antiphosphotyrosine antibodies. The DPV-induced [32P] PBt-accumulation was
inhibited by putative tyrosine kinase inhibitors such as genistein, herbimycin,
tyrphostin and by chelation of Ca2+ with either EGTA or BAPTA, however,
pretreatment of BPAECs with the inhibitor PKC bisindolylmaleimide showed minimal
inhibition. Also down-regulation of PKC alpha and epsilon, the major isotypes of
PKC in BPAECs, by TPA (100 nM, 18 h) did not attenuate the DPV-induced PLD
activation. The effects of putative tyrosine kinase and PKC inhibitors were
specific as determined by comparing [32P] PBt formation between DPV and TPA. In
addition to tyrosine kinase inhibitors, antioxidants such as N-acetylcysteine and
pyrrolidine dithiocarbamate also attenuated DPV-induced protein tyrosine
phosphorylation and PLD stimulation. These results suggest that oxidation,
prevented by reduction with thiol compounds, is involved in DPV-dependent protein
tyrosine phosphorylation and PLD activation.
PMID- 9655186
TI - Physiological consequences of expression of the Na+/H+ antiporter sod2 in
Escherichia coli.
AB - Sod2 is the sodium-proton antiporter on the plasma membrane of the fission yeast
Schizosaccharomyces pombe. It is vitally important for sodium export and pH
homeostasis in this organism. Recently, the sod2 gene has been cloned and
sequenced. However, initial attempts to express sod2 in Escherichia coli using
the T7 promoter failed. In the present work we examined physiological
consequences of expression of sod2 in E. coli. To alleviate problems caused by
expression of sod2 we: (i) used sodium-free media at all steps; (ii) used the
moderate tac promoter for expression and; (iii) used E. coli strain MH1 which has
impaired sodium exchange. The effect of sod2 expression on E. coli varied
depending on the E. coli genotype. When sod2 was expressed in BL21 cells which
have normal Na+/H+ antiporters, the result was a Li+ sensitive phenotype. LiCl
completely arrested or prevented growth of BL21 E. coli transformed with the sod2
gene. The effect on growth was pronounced in media of low external pH. Sod2 was
then expressed in E. coli MH1 which is devoid of endogenous Na+/H+ antiporters.
These cells became more resistant to external LiCl, but only in Na+ containing
media. In the absence of external Na+, the presence of sod2 reduced growth. The
results are explained in a model which demonstrates the physiological
consequences of interference by expression of a foreign electroneutral Na+/H+
antiporter in conjunction with different housekeeping systems of E. coli host
cells.
PMID- 9655187
TI - Role of liposomes in selective proliferation of splenic lymphocytes.
AB - The effects of free and encapsulated allergens of Artemisia scoparia pollen on
lymphocyte proliferation and immunoglobulin production in BALB/c mice were
investigated. Splenic lymphocytes from mice immunized with liposome entrapped
allergen (LEA) elicited a marked proliferative response upon in vitro stimulation
with both free and encapsulated allergen in comparison to mice immunized with
free allergen (FA). The serum immunoglobulin profile of mice administered LEA
revealed a predominance of IgG1 antibodies concomitant with an enhancement of
IgG2a, IgG2b, IgG3 and IgM responses and suppression of IgE responses. However
immunization with FA resulted in significant production of IgE responses and low
levels of IgG antibodies. The differential ability of free and encapsulated
allergens to selectively induce immunoglobulin isotypes suggests that different
presentation and T cell differentiation pathways may be followed by FA and LEA in
the immune system. Proliferation studies involving macrophage depletion
demonstrated that macrophages play an obligatory role in the processing of LEA.
Analysis of cytokine production in sera of immunized mice (FA/LEA) revealed that
LEA induced significant IFN-gamma responses and lower IL-4 responses than mice
immunized with FA. The results of the present study indicate that liposomes
synergise the proliferation by the antigen incorporated in it and polarizes the
response towards Th1 type of cytokine production. The immunoadjuvant and
immunomodulation property of liposomes make it an efficient vehicle for effective
immunotherapy.
PMID- 9655188
TI - In vivo oxidized low density lipoprotein: degree of lipoprotein oxidation does
not correlate with its atherogenic properties.
AB - We have recently demonstrated that lipids, particularly cholesterol, covalently
bound to apolipoprotein B (apoB) are a stable marker of low density lipoprotein
(LDL) oxidation (Tertov et al. 1995). The present study is an attempt to assess
the relationship between the degree of LDL oxidation, evaluated by the content of
apoB-bound cholesterol and the ability of LDL to induce cholesterol accumulation
in cultured human aortic intimal smooth muscle cells, i.e. LDL atherogenicity.
Native LDL was oxidized in vitro by copper ions, 2,2-azobis-(2-aminopropane
hydrochloride), or sodium hypochlorite. Minimum degree of LDL in vitro oxidation
necessary to convert LDL into atherogenic one was accompanied by an increase of
apoB-bound cholesterol to the level much higher than that usually observed in
freshly isolated atherogenic LDL from human blood. Moreover, elimination of LDL
aggregates from in vitro oxidized LDL preparations by gel filtration led to loss
of its atherogenic properties. Thus, the ability to induce cholesterol
accumulation in cells, i.e. the atherogenicity of in vitro oxidized LDL is a
result of LDL aggregation but not oxidation. We also studied the relationship
between LDL atherogenicity and apoB-bound cholesterol content in LDL freshly
isolated from healthy subjects and normo- and hypercholesterolemic patients with
coronary atherosclerosis. The ability of human LDL to induce cholesterol
accumulation in aortic smooth muscle cells did not correlate with the degree of
in vivo LDL oxidation (r = 0.12, n = 90). It is concluded that LDL atherogenicity
does not depend on the degree of lipid peroxidation in LDL particle.
PMID- 9655189
TI - Effects of peroxide on endothelial nitric oxide synthase in coronary arteries.
AB - Reactive oxygen species (ROS) are produced in ischemia and reperfusion. Since
endothelial nitric oxide synthase (eNOS) is key to the endothelium-dependent
vasodilation, we examined the effects of peroxide on this enzyme. We treated
cells cultured from pig coronary artery endothelium with different concentrations
of hydrogen peroxide, washed them, solubilized them and measured NOS activity by
arginine to citrulline conversion. Hydrogen peroxide inhibited the eNOS activity
with an IC50 value of 0.85 +/- 0.39 mM. In another experiment, we perfused
arteries with solutions containing 0 or 1 mM hydrogen peroxide, washed them,
removed the endothelium using a cotton swab, centrifuged and solubilized the
endothelium and monitored its NOS activity. Hydrogen peroxide (1 mM) did not
affect the NOS activity significantly (p > 0.05) in this assay. We conclude that
the inactivation of eNOS by hydrogen peroxide does not play a major role in the
ischemia-reperfusion damage because the peroxide concentrations attained during
ischemia-perfusion are much lower than those affecting the eNOS activity.
PMID- 9655190
TI - Biophysical characterization of rat cardiac Ca2+/Mg2+ ecto-ATPase (myoglein).
AB - Sarcolemmal Ca2+/Mg2+ ecto-ATPase (Myoglein; MW 180 kD) is a membrane bound
enzyme which requires a millimolar concentration of either Ca2+ or Mg2+ for
maximal hydrolysis of ATP. The isoelectric point (pI) of the cardiac ecto-ATPase
was 5.7. The purified Ca2+/Mg2+ ecto-ATPase from the rat heart sarcolemmal
appeared as a single band with MW approximately 90 kD in the SDS-PAGE. In order
to understand the nature of this enzyme, the 90 kD band in the SDS-PAGE was
electroeluted; the analysis of the eluate showed 2 prominent bands with MW
approximately 90 and 85 kD. The presence of 2 bands was further confirmed by
gradient gel (10-20%) electrophoresis in 0.375 M Tris-HCl buffer, pH 8.8.
Analysis of the purified Ca2+/Mg2+ ecto-ATPase as well as the electroeluted
protein in a non-equilibrium linear two dimensional electrophoresis (Ampholyte pI
3.0-10.0) also showed two distinct bands. Mass spectroscopic analysis of the
enzyme using different matrix combinations revealed the presence of multi
components indicating microheterogeneity in the protein structure. Treatment of
the ecto-ATPase with DL-dithiothreitol did not alter the pattern of mass
spectroscopic analysis and this indicated that the microheterogeneity may be due
to some posttranslational modifications. It is concluded that rat cardiac
Ca2+/Mg2+ ecto-ATPase is an acidic protein having two subunits. Furthermore, the
enzyme shows microheterogeneity in its molecular structure.
PMID- 9655191
TI - Effect of polar glycopeptidolipids from Mycobacterium chelonae (GPLp-Mc) on
phagocytosis and superoxide anion production of macrophages from mice. Influence
of physical activity.
AB - It is not clear how macrophages respond to exercise when the immune system is
previously activated. The aim of the present work was to determine the response
of macrophages to exercise in already immunostimulated animals with polar
glycopeptidolipids extracted from Mycobacterium chelonae (GPLp-Mc). Results
showed an increased phagocytosis and O2- production in murine macrophages induced
by the intraperitoneal administration of 25 mg/kg body weight of GPLp-Mc. In
addition exercise stimulated phagocytic activity and decreased the O2- production
of these cells. Unexpectedly, exercise did not potentiate the immunostimulatory
effect of GPLp-Mc. However, we can conclude that the effect of exercise is not
detrimental to immunostimulated animals.
PMID- 9655192
TI - Seasonal variation in haematological parameters in male and female Tinca tinca.
AB - This study was designed to investigate any seasonal (spring, summer, autumn and
winter) changes in haematological parameters in the blood of Tinca tinca
measuring the number of red blood cells (RBC), haematocrit, white blood cells,
and total plasma proteins. The results show significant changes in RBC and
haematocrit in males comparing spring and summer with autumn and winter, whereas
in females the RBC remained constant for all 4 seasons but the haematocrit
decreased in autumn and winter compared to spring and summer. The white blood
cells of male and female animals were significantly lower in spring and winter
compared to summer and autumn. In male fish total protein contents significantly
decreased in autumn and winter compared to spring and summer, whereas in females
protein output significantly decreased in winter compared to the other seasons.
The results indicate marked seasonal variation in the blood of male and female
Tinca tinca. This variation may play a important protective role for the survival
of the animals.
PMID- 9655193
TI - The effect of hexadecylphosphocholine on the degradation of mitochondrial
phospholipids.
AB - Hexadecylphosphocholine (HePC) is known as antitumor agent but the mechanism has
not yet been understood. In rat liver mitochondria its effect on phospholipid
transformation has been studied by quantitative HPTLC and phosphorus
determination. From the results it can be concluded that HePC influences the
activities of phospholipase A2, phospholipase C, phospholipase D, and
lysophospholipase A. The phospholipid transformation as well as the influence of
HePC are affected by exogenous calcium ions. In the presence of calcium HePC has
been found to inhibit enzyme activities, whereas in the absence of exogenous
calcium ions enzymatic phospholipid transformations are activated or inhibited
depending on HePC concentrations.
PMID- 9655194
TI - Stimulation by hexose esters of lactate production by rat erythrocytes:
insensitivity to 3-O-methyl-D-glucose and inhibition by 2-deoxy-D-glucose and its
tetraacetic ester.
AB - Selected esters of D-glucose were recently proposed as tools to provide the sugar
to cells, whilst bypassing the carrier system for hexose transport across the
plasma membrane. In the present study, alpha-D-glucose pentaacetate, beta-D
glucose pentaacetate, alpha-D-mannose pentaacetate and, to a lesser extent, 6-O
acetyl-D-glucose, all tested at a 1.7 mM concentration, were found to increase
lactate production above basal value in rat erythrocytes. Over 90 min incubation,
the increment in lactate production ranged from about 1.2 (alpha-D-glucose
pentaacetate) to 0.6 (6-O-acetyl-D-glucose) micromol/microl of erythrocytes.
Little or no change in lactate production was observed in cells exposed to beta-L
glucose pentaacetate, alpha-D-glucose pentaethylsuccinate, alpha-D-galactose
pentaacetate or beta-D-galactose pentaacetate. The metabolic response to alpha-D
glucose pentaacetate was resistant to 3-O-methyl-D-glucose (10-80 mM) which
suppressed, however, that evoked by D-glucose. D-mannoheptulose (10 mM) virtually
failed to affect the response to D-glucose and its pentaacetate ester. On the
contrary, 2-deoxy-D-glucose (10.6 mM) inhibited to the same relative extent (55%
decrease) lactate production in erythrocytes exposed to either unesterified D
glucose or alpha-D-glucose pentaacetate. The tetraacetic ester of 2-deoxy-D
glucose was more efficient than unesterified 2-deoxy-D-glucose in inhibiting
lactate production from alpha-D-glucose pentaacetate. It is proposed that
selected esters of saccharides represent useful tools to bypass defects in hexose
transport, and to increase their nutritional or therapeutic efficiency.
PMID- 9655195
TI - Ca2+/calmodulin dependent protein kinase from Mycobacterium smegmatis ATCC 607.
AB - A soluble Ca2+/calmodulin dependent protein kinase has been partially purified
(approximately 400 fold) from Mycobacterium smegmatis ATCC 607 using several
purification steps like ammonium sulphate precipitation (30-60%), Sepharose CL-6B
gel filtration, DEAE-cellulose and finally calmodulin-agarose affinity
chromatography. On SDS-PAGE, this enzyme preparation showed a major protein band
of molecular mass 35 kD and its activity was dependent on calcium, calmodulin and
ATP when measured under saturating histone IIs (exogenous substrate)
concentration. Phosphorylation of histone IIs was inhibited by W-7 (calmodulin
inhibitor) and KN-62 (CaM-kinase inhibitor) with IC50 of 1.5 and 0.25 microm
respectively, but was not affected by inhibitors of PKA (Sigma P5015) and PKC (H
7). All these results confirm that purified enzyme is Ca2+/calmodulin dependent
protein kinase of M. smegmatis. The protein kinase of M. smegmatis demonstrated a
narrow substrate specificity for both exogenous as well as endogenous substrates.
These results suggest that purified CaM-kinase must be involved in regulating
specific function(s) in this organism.
PMID- 9655196
TI - Insulin-induced Glut4 recruitment in the fatty Zucker rat heart is not associated
with changes in Glut4 content in the intracellular membrane.
AB - Impaired cardiac glucose metabolism and glucose transport have been shown in the
insulin resistant fatty Zucker rat. The aim of the present study was to examine
the translocation of the insulin-sensitive glucose transporter (Glut4) in the
heart of the fatty Zucker rat under in vivo conditions. Insulin was injected into
both lean (FA/?) and fatty (fa/fa) Zucker rats via the tail vein. The time course
of cardiac Glut4 translocation was studied by determining the subcellular
distribution of Glut4 using a newly developed ELISA quantitation method. Insulin
(10 U/kg) caused a 30% and 37% increase in plasma membrane Glut4 content at 20
min after injection in lean and fatty rats respectively. The plasma membrane
Glut4 contents in the basal and insulin-stimulated states were significantly
lower in the fatty rat when compared to the lean control. The dose effect of
insulin (2.5-10 U/kg) on Glut4 mobilization to the plasma membrane was similar in
both phenotypes. The time course of Glut4 mobilization to the plasma membrane (5
30 min), which was similar in both lean and fatty Zucker rats, showed that
maximal translocation was reached at 5 min post insulin injection and persisted
throughout the remaining 25 min. However, in fatty Zucker rats, Glut4 content in
the intracellular membrane remained unchanged at all insulin doses and all time
points studied. Collectively, these results show that Glut4 recruitment to the
plasma membrane is responsive to insulin in the fatty Zucker rat heart and that
the maximal response was similar to that in lean Zucker rats. However, the
recruitment of Glut4 to the plasma membrane was not associated with changes in
the intracellular membrane Glut4 content.
PMID- 9655197
TI - Phosphorylation of stathmin modulates its function as a microtubule
depolymerizing factor.
AB - Oncoprotein 18 or stathmin was isolated from bovine brain, characterized and
novel features of its function as a microtubule depolymerizing factor were
tested. The effect of phosphorylation of stathmin on its function as a
microtubule depolymerizing factor has been tested in vitro. Five different
protein kinases, protein kinase A, MAP kinase, cdc2 kinase, glycogen synthase
kinase 3 and casein kinase 2, were used to modify stathmin, since it is known
that these kinases could phosphorylate several residues that are modified in vivo
and could have important roles in stathmin function. The residues phosphorylated
in vitro by the different protein kinases were identified and in some cases they
correspond to those modified in vivo. Recombinant unphosphorylated stathmin and
native stathmin, which was previously dephosphorylated with alkaline phosphatase,
showed similar microtubule depolymerizing activity. This activity is higher than
that of stathmin phosphorylated by protein kinase A, MAP kinase or cdc 2 kinase,
whereas phosphorylation of the protein with casein kinase 2 or glycogen synthase
kinase 3 resulted in a slight increase of the depolymerizing activity.
PMID- 9655198
TI - Erythrocytes from healthy smokers bind more bilirubin than the erythrocytes from
healthy non-smokers.
AB - Cigarette smoking is an adverse prognostic factor for health. Its damaging
effects on many enzymatic and cellular activities are well known. The present
study was carried out to evaluate whether there is a difference in the binding of
bilirubin to the erythrocytes from healthy smokers and non-smokers. The results
suggest that the binding of bilirubin to the erythrocytes from healthy smokers as
well as in vitro smoked erythrocytes is significantly higher than that of healthy
non-smokers.
PMID- 9655199
TI - Depletion of endogenous dopamine stores and shift in beta-adrenoceptor subtypes
in cardiac tissue following five weeks of chronic denervation.
AB - Surgical ablation of extrinsic cardiac nerve fibers results in a chronically
denervated state of the left ventricle of the heart. The present study was
performed to elucidate the effect of a period of 5 weeks of chronic denervation
on cardiac catecholamine levels in general and dopamine in particular. Moreover,
the possible effect on cardiac beta-adrenoceptor subtypes was investigated.
Experiments were performed on adult dogs. In addition to adrenaline and
noradrenaline the tissue levels of dopamine were found to be severely depressed.
A significant shift from beta1- to beta2-adrenoceptor subtype was observed, while
the total beta-adrenoceptor density remained unaffected. The present findings
indicate that catecholamine synthesis in chronically denervated hearts is
impaired upstream of dopamine and that a shift in beta-adrenoceptor subtype
occurs already within a relatively short period of five weeks of denervation, and
suggest that the lack of endogenous catecholamines influence the relative
expression levels of the two subtypes of beta-adrenoceptors present in cardiac
tissue.
PMID- 9655200
TI - Postural control in benign paroxysmal positional vertigo before and after
recovery.
AB - Thirty-two patients affected by idiopathic benign paroxysmal positional vertigo
(BPPV) of the posterior semicircular canal were studied before, 3 days and I
month after a resolutive Semont manoeuvre by means of dynamic posturography. The
overall postural control in BPPV patients was shown to be impaired, as
demonstrated by the pathological equilibrium scores. Data obtained before
treatment showed a specific pattern of vestibular involvement and a pathological
composite score. After the liberatory manoeuvre the Sensory Organization Test
indicated a significant improvement in the pathological composite and vestibular
scores. However, significant differences from controls were still detected 3 days
and 1 month after clinical recovery from BPPV. The results clearly show that, in
BPPV patients, there is an impairment of the vestibular system, which seems
unable to maintain a normal postural balance. This deficit can be particularly
detected when dynamic posturography evaluates the vestibular cues. After the
liberatory manoeuvre a consistent improvement in the overall postural control has
been observed but the residual differences from controls seem to suggest that
damage to the otoconial maculae influences postural control, even when there is
significant improvement in the clinical signs.
PMID- 9655201
TI - Intratympanic gentamicin in Meniere's disease.
AB - Ninety-three patients with intractable Meniere's disease were treated with
gentamicin (Garamycin 40 mg/ml) administered in 1 to 4 transtympanic injections.
The patients were tested at frequent intervals and followed up for 2 years.
Before treatment all subjects experienced moderate or severe handicap caused by
Meniere's disease. Two years after the treatment, rotatory vertigo was abolished
in 81% of subjects, Tumarkin attacks were cured in 60%, and work capacity was
severely reduced in 10% and moderately reduced in 17% of subjects. The outcome of
the caloric responses did not correlate with the outcome of the treatment. In
logistic regression analysis poor outcome of treatment correlated with Tumarkin
attacks (odds ratio 5.5), severity of vertigo (odds ratio 3.8) and gait disorders
(odds ratio 2.9). The mean hearing level was significantly affected by the
treatment (before, 59.1 dB HL; after, 67.9 dB HL). Ten treated ears became
deafened. During follow-up 44 subjects were subjected to retreatment, usually
after 6 months. Intratympanic gentamicin treatment is a relatively safe and
effective way to treat Meniere's disease. The authors recommended starting with 2
injections and renewing the injections if relapse occurs.
PMID- 9655202
TI - The subjective visual horizontal after stapedotomy: evidence for an increased
resting activity in otolithic afferents.
AB - The subjective visual horizontal (SVH) was measured by means of a small rotatable
luminous line in darkness in the upright body position and at 10, 20 and 30
degrees of body tilt to the right and left prior to, and during a follow-up
period after, stapedotomy in 12 patients with otosclerosis. In the acute stage
after surgery, SVH in the upright body position was significantly tilted away
from the operated side. In addition, the perception of roll tilt towards the
operated side (Kop) was significantly increased after stapedotomy, while the
perception of roll tilt towards the healthy side (Khe) showed a slight but not
significant reduction. After exclusion of two outliers, a statistically
significant correlation was found between changes in Kop and in Khe. The slope of
the regression line was 1.8:1, probably corresponding to a preference of the
utricle for ipsilateral as opposed to contralateral head tilt. In four patients
there was a weak ( < 1 degrees/s) spontaneous nystagmus, not systematically
related to the side of surgery, while in most cases there were no nystagmus or
subjective vertigo symptoms. These specific changes in the subjective horizontal
show that the otolithic effects on perception can be dissociated from canal
effects. Further, the results are opposite to those for patients with unilateral
loss of vestibular function. The tilt of SVH after stapedotomy indicates an
increase in resting activity of utricular afferents. In addition, based on recent
theories on otolith function, we suggest that an increased activity in saccular
afferents is of major importance for the changes in roll-tilt perception because
of its interaction with the utricle on the central nervous level.
PMID- 9655203
TI - Effect of probe frequency and gender on click-evoked ipsilateral acoustic reflex
thresholds.
AB - This study was designed to evaluate the effects of gender and probe frequency on
the ipsilateral click-evoked acoustic reflex thresholds. Ipsilateral acoustic
reflex thresholds were obtained from the left ear of each subject (12 male and 12
female normal young adults) by presenting clicks at the rate of 180/sec. The
probe tone frequencies were 226, 678 and 1.000 Hz. The results revealed that
acoustic reflex thresholds for the 678 Hz probe were significantly higher than
those obtained with the 226 and 1.000 Hz probes. No gender differences were
apparent. However, the static admittance was significantly correlated with the
acoustic reflex thresholds for the 678 Hz probe in only the female subjects. For
the 226 Hz probe, the elicitation of the reflex resulted in a decrease in static
admittance in all the subjects. For the 678 Hz probe, the admittance decreased in
58% of the subjects and it increased in 42% of the subjects. For the 1,000 Hz
probe, an increase in admittance was apparent in all of the subjects. The results
suggest that either the 226 Hz or the 1,000 Hz probes can be used for the
measurement of click-evoked acoustic reflex thresholds in adults.
PMID- 9655204
TI - Intracochlear factors contributing to psychophysical percepts following cochlear
implantation.
AB - The performance of cochlear implant patients may be related to intracochlear,
histopathological factors. We have performed detailed post-mortem examinations of
five human, implanted cochleas and for each electrode correlated the
psychophysical threshold, comfortable level and dynamic range with spiral
ganglion cell survival, presence of fibrous tissue and/or new bone, and distance
between the centers of the electrode bands and Rosenthal's canal. The
psychophysical parameters were strongly interrelated. Threshold and comfort
levels correlated with the distance between the electrodes and Rosenthal's canal.
Threshold levels also correlated with the presence of intracochlear fibrous
tissue and new bone, especially with the former. The dynamic range showed a
negative correlation with intracochlear pathology, especially with new bone.
Comfort levels and dynamic range were related to spiral ganglion cell survival.
The distance between the electrodes and the modiolus increased with increasing
levels of fibrous tissue and new bone. Spiral ganglion cell survival was
decreased with increasing levels of fibrous tissue and new bone.
PMID- 9655205
TI - Acoustic neuroma/vestibular schwannoma growth: past, present and future.
AB - The growth of vestibular schwannoma (VS) was investigated in a series of 123
patients with 127 tumors in the period 1973 1993. The material was reanalysed and
updated 3 years later in 1996. By termination of the first observation period
(mean 3.4 years), 94 tumors (74%) exhibited measurable growth, 23 tumors (18%) no
measurable growth and 10 tumors (8%) negative growth. By the end of the extended
observation period (mean 3.8 years), tumor growth was observed in 104 tumors
(82%), no tumor growth in 15 tumors (12%) and negative growth in eight tumors
(6%). Several growth patterns were noticed: however, these were not static as the
growth patterns of the tumors changed during the extended observation period.
Accordingly, the expected growth figures by the end of this century (mean
observation period approximately 4 years) will probably be: growth in 111 tumors
(87%), no growth in 10 tumors (8%) and negative growth in six tumors (5%). The
results indicate that neither the present study nor the previously published
studies on tumor growth reflect the natural history of VS, but they only provide
information on tumor growth, growth rates and growth patterns during a given
observation period.
PMID- 9655206
TI - The endolymphatic sac receives antigenetic information from the organs of the
mucosa-associated lymphatic system.
AB - The endolymphatic sac holds the entire arrangement of immunocompetent cells and
functions as an immunological potent control organ for the inner ear. The
evidence of secretory immunoglobulin A and other features of lymphocyte subtypes
characterizes the endolymphatic sac as an organ of the mucosa-associated
lymphatic system (MALT). In this system a permanent recirculation of sensitized
memory lymphocytes from one organ to the other has been demonstrated
experimentally as serving to dispose memory lymphocytes after renewed antigenetic
stimulus. The aim of this study was to prove the possible recirculation of
antigen-sensitized lymphocytes to the endolymphatic sac after antigenic stimulus
of another part of the mucosa-associated lymphatic system. The results are
evidence that the endolymphatic sac is provided with immunocompetent cells which
derive from the lymphatic tissue of the nasopharynx. While the origin of
immunocompetent cells in the endolymphatic sac still remains uncertain, this
study underlines the role of lympho-epithelial tissue of the nasopharynx as a
possible cell source for the endolymphatic sac. The results might explain the
altered or disturbed function of the endolymphatic sac as a possible cause of
certain inner ear diseases.
PMID- 9655207
TI - Effects of transforming growth factor-beta1 and basic fibroblast growth factor on
proliferation of cell cultures derived from human vestibular nerve schwannoma.
AB - The influence of transforming growth factor-beta1 (TGF-beta1) and basic
fibroblast growth factor (bFGF) on growth of cell cultures derived from
unilateral vestibular nerve schwannomas was investigated. Cell cultures were
initiated from 9 schwannomas and characterized immunocytochemically with
antibodies against S-100 and type IV collagen. The effects of TGF-beta1 and bFGF
on DNA synthesis in chemically defined serum-free medium were assessed by
measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA.
Cell proliferation was evaluated with an electronic cell counter. Reverse
transcription polymerase chain reaction (RT-PCR) was performed using
oligonucleotide primers specific for TGF-beta1 and TGF-beta2. TGF-beta1
stimulated DNA synthesis in a dose dependent manner. Maximal stimulation was
observed at a concentration of 1 ng/ml, which induced a nearly 2-fold increase in
DNA content. This effect was not seen when TGF-beta1 was added in the presence of
neutralizing antibodies. In addition, antibodies against TGF-beta1 significantly
reduced DNA synthesis in control cultures without supplemented exogenous growth
factors. bFGF alone had no significant effects on DNA synthesis. In contrast,
when TGF-beta1 and bFGF were added together, the mitogenic response was much
greater than produced by TGF-beta1 alone. RT-PCR showed that the cultured cells
expressed mRNA for both TGF-beta1 and TGF-beta2. We hypothesize that TGF-beta1 is
an autocrine growth factor for human vestibular nerve schwannomas in culture. A
similar mechanism might be involved in the growth of these tumors in situ.
PMID- 9655208
TI - Perikaryal myelination of cultured chick embryo statoacoustic ganglion cells: an
electron microscopic study.
AB - Perikaryal myelin formation on cultured chick embryo statoacoustic ganglion (SAG)
cells was studied using electron microscopy. SAGs were dissected from 13-day
embryos and cultured for 1 to 6 weeks. Myelinated perikarya, which were
completely encircled by two or more layers of loose and/or compact myelin
lamellae like those in vivo in the chick, were first observed in 3-week-cultured
SAGs; myelinated axons appeared in 2-week-cultured SAGs. The perikaryal
myelination progressively increased loose and compact lamellae and the axonal
myelination increased compact lamellae. In 4- to 6-week-cultured SAGs, 11 to 12%
of SAG cells had the myelinated perikaryon of which perikaryal myelin lamellae
terminated at the axon hillock in the same manner as those in vivo in the chick.
The number of layers of myelin lamellae around the myelinated perikaryon in 5- to
6-week-cultured SAGs and around the myelinated axon in 4- to 6-week-cultured SAGs
ranged between 2 and 15, and between 12 and 26, respectively. Since these numbers
were consistent with those in vivo in chicks 3 days after hatching, it is
suggested that the culture provides perikaryal myelin sheaths, which are
equivalent to those in vivo in structure, in more than 10% of SAG cells, while
the myelination process in vitro is carried out much more slowly than that in
vivo.
PMID- 9655209
TI - An in vitro model for acoustic overstimulation.
AB - Although many studies have been performed on the effects of acoustic
overstimulation on the inner ear, our knowledge about the cellular processes
underlying reduced hearing sensitivity and auditory cell death is still limited.
In order to further our understanding of cellular processes occurring in
conjunction with acoustic trauma, we designed an in vitro model to study the
effects of overstimulation directly on sensory hair cells isolated from the low
frequency part of the guinea pig cochlea. The isolated outer hair cells were
subjected to pressure jets delivered by a glass micropipette positioned close to
the cell, in order to mimic the pressure changes occurring in the intact inner
ear during sound stimulation. A second micropipette coupled to a piezoresistive
pressure transducer was used as a probe measuring the pressure at precise
locations at and around the cell. In a previous study, we found that such
stimulation gave rise to increases in the intracellular calcium concentration.
The present study characterizes the stimulus, describes the computer-controlled
setup used for calibration, and gives examples of different modes of
overstimulation at the cellular level. The peak pressure that could be generated
using the pressure jet was around 325 Pa, or 144 dB (re 20 microPa) at 140 Hz.
The pressure jet elicited large mechanical vibrations of the cell bodies of
isolated cells. The vibration mode of the cells often changed over time, implying
that the stimulation caused changes of the cellular stiffness. However, most
cells appeared quite resistant to the high intensity mechanical stimulation.
PMID- 9655210
TI - Experimental study on the effects of gentamicin injection on the guinea-pig:
electrophysiological studies.
AB - The inner ear distortion induced by gentamicin (GM), a type of aminoglycoside
antibiotic, was examined in guinea-pigs. Previous studies which investigated the
function of the eighth cranial nerve and organ of Corti using cochlear
microphonics (CM) and compound action potential (CAP) reported ototoxicity
following experimental exposure to GM. In this report, the effects of GM on the
cochlea and the eighth cranial nerve were investigated systematically by
measuring CM, CAP, summating potentials induced by 90 dB (SPL) tone burst,
endocochlear potential (EP) and K+ ion concentration of the endolymph. Guinea
pigs were treated with a daily intramuscular injection of GM (60 mg in 1.5 cc) at
a dose of 60 mg/kg during different treatment periods. The maximum output voltage
of AP was decreased by injection of GM (60 mg/kg x 24). A decrease in the CM
maximum output voltage and the elevation of CM pseudothreshold were typically
seen after GM injection at a test frequency of 8 kHz and a decrease in CAP was
also observed. Changes in EP during 3 min anoxia were observed, in particular a
decrease in the absolute value of the negative potential. The endolymph K+ ion
concentration remained unchanged. These findings indicate that the diffusion
potentials decreased at the same time as reduction of maximum output voltage in
CM induced by GM injection.
PMID- 9655211
TI - Continuous long-term measurements of the middle ear pressure in subjects without
a history of ear disease.
AB - A new method was used for continuous measurement of the middle ear (ME) pressure
during a 24-h period. In 10 subjects without a history of ear disease a small
perforation was made through the tympanic membrane. A tight rubber stopper
containing a small polyethylene tube was fitted into the external ear canal.
Conventional tubal function tests were performed. The equipment was then carried
by the subjects for 24 h of normal activity to monitor any slow or rapid dynamic
pressure change in the ME. Body position was found to be the most important
factor affecting ME pressure variation, during the 24-h continuous pressure
measurements. A significant pressure rise occurred in the recumbent position in
all but one subject. Few rapid pressure equilibrations were seen during the
recordings, indicating few tubal openings. This implies that the pressure changes
in the ME seen in this study were mainly the result of gas exchange over the
mucosa. The investigation might be a base for reference when investigating
different kinds of pathologic conditions in the ear.
PMID- 9655212
TI - Elevated autoantibodies in sera from otosclerotic patients are related to the
disease duration.
AB - In this study an indirect ELISA with patients' sera was performed using human
collagen type II, double- (dsDNA) and single-stranded DNA (ssDNA), thyroid
microsomal antigen, insulin and lysozyme as antigens. Since many preoperated
otosclerotic patients demonstrated the signs of myringosclerosis (n=7). they were
classified separately and compared with otosclerotic patients without
myringosclerosis (n=28), with healthy controls (n=42) and with patients with
tympanosclerosis (n=5) of other origin. The otosclerotic patients had serum
antibodies to antigens tested similar to normal controls. However, elevated
antibody levels to human collagen type II, dsDNA and ssDNA were observed only in
patients with a disease duration between 3 and 5 years as compared to other
otosclerotic patients. The same duration association was observed in the level of
the total serum alkaline phosphatase activity. These observations would suggest
that the enzymatic bone resorption is the driving force in human otosclerosis.
Elevated serum autoantibodies during tissue reparation in the otosclerotic stage
may be a transient response to sustained excess antigen turnover in the primary
lesion.
PMID- 9655213
TI - Ribotyping of strains of Moraxella (Branhamella) catarrhalis cultured from the
nasopharynx and middle ear of children with otitis media.
AB - Moraxella (Branhaomella) catarrhalis is frequently present in the nasopharyngeal
microflora of small children, especially during episodes of acute otitis media .
By means of ribotyping (restriction endonuclease analysis of chromosomal DNA
combined with rRNA probing), we studied the genetic heterogeneity of 78 cultures
of M. catarrhalis obtained from different localities in the nasopharynx of nine
young children with secretory otitis media. Using HindIII and PstI as
endonucleases, five different ribotypes were recognized, representing at least
five different genotypes of M. catarrhalis. The distribution of these types was
found to be almost identical to the distribution among 16 M. catarrhalis strains
cultured from middle ear exudates of 16 children with acute otitis media.
Ribotype HAPA was found in two-thirds of all the cultures investigated, and 44%
of the children harboured more than one ribotype in the nasopharynx at the same
time. The vast majority of the nasopharyngeal M. catarrhalis cultures were beta
lactamase positive. One child had both a HAPA ribotype, beta-lactamase-negative
strain in the nasopharyngeal secretions, and HAPA ribotype, beta-lactamase
positive strains at the entrance of the eustachian tube, the nasopharyngeal
tonsils, the folds of the nasopharyngeal tonsils and the oropharynx. All except
one of the M. catarrhalis strains cultured from middle ear exudates were beta
lactamase positive.
PMID- 9655214
TI - Different production of interleukin-1alpha, interleukin-1beta and interleukin-8
from cholesteatomatous and normal epithelium.
AB - Cholesteatomatous bone destruction is caused by an increase in collagenase
activity and activation of the osteoclasts. Cytokines. such as interleukins (IL),
are important in intercellular communication in the mechanism of bone
destruction. Middle ear cholesteatomas and external auditory canal skins (EACS)
can be surgically obtained and cultured. The quantities of IL-1alpha, IL-1beta
and IL-8 secretions were measured in the supernatant of each culture series. On
the 2nd day of culture, the level of IL-1alpha was 0.60+/-0.13 (pg/microg of
total protein) in cholesteatoma, and 0.25+/-0.02 in EACS. The levels of IL-1beta
in cholesteatoma and EACS were 0.41+/-0.06 and 0.24+/-0.02, respectively. The
levels of IL-8 in cholesteatoma and EACS were 146.50+/-32.37 and 50.40+/-6.24,
respectively. After 2 days, the levels of IL-1alpha and IL-8 of each tissue
decreased. The value from fibroblasts did not show a significant difference
between cholesteatoma and EACS, and the values did not change as time passed. We
can conclude that the IL-1alpha and IL-8 from the cholesteatomatous epithelium
are responsible for the cholesteatomatous bone destruction and certain substances
from the subepithelial granulation tissue can stimulate the cholesteatoma to
produce IL-1alpha and IL-8.
PMID- 9655215
TI - Late phase response in nasal mucosa closely correlated with immediate phase
reaction and hyperreactivity to histamine.
AB - It has been suggested that the onset of the late phase response (LPR) and
hyperreactivity to non-specific stimuli occurs in the lower airway. However, its
relationship in the nose has not yet been studied. This study was designed to
examine the mechanism of LPR and the relationship between LPR and
hyperreactivity. A total of 25 Japanese cedar pollinosis patients participated in
this study. On the first visit, the frequency of sneezes, weight of nasal
discharge, and the nasal airway resistance (NAR) were time-dependently measured
without antigen challenge. The histamine reactivity was observed after 12 h. The
same protocol was used during the second to fourth visits. The frequency of
sneezes, weight of nasal discharge, and NAR were measured continuously for 12 h
after antigen challenge, and nasal reactivity to histamine was observed. The
percent change of NAR during immediate phase response (IR) and during LPR showed
a significant correlation. The frequency of sneezes and weight of nasal discharge
induced by histamine were both significantly higher in the positive than in the
negative LPR group. These results suggest that the chemical mediators and
inflammatory cells inducing nasal swelling during IR cause, directly or
indirectly, nasal swelling during LPR, and induce hyperreactivity to histamine.
PMID- 9655216
TI - Distribution and quantity of neuroendocrine markers in allergic rhinitis.
AB - Neuroendocrine components exist in the human nasal mucosa. However, the
pathophysiological and neuroimmunological roles of the regulatory peptides in
allergic rhinitis (AR) require further investigation. To analyse the functional
morphology and quantify the tissue concentration of regulatory peptides in the
nasal mucosa of AR subjects, human inferior turbinate mucosa specimens from 25
patients with AR, 20 patients with non-allergic rhinitis and 10 patients without
any nasal diseases were investigated. Using immunohistochemistry and
radioimmunoassays, we detected the presence, distribution and concentrations of
various neuropeptides [vasoactive intestinal peptide (VIP), neuropeptide Y (NPY),
substance P (SP) and calcitonin gene-related peptide (CGRP)] and general
neuroendocrine markers (neuron-specific enolase and chromogranin A). Quantitative
analysis of the stained fibres and cells was performed using a graphic AutoCAD
program. The presence and distribution of NPY, CGRP and SP nerve fibres and
neuroendocrine cells were similar among the three subject groups. AR subjects had
significantly higher tissue concentrations of VIP and SP. AR subjects had
increased numbers of VIP fibres which predominantly innervated vessels. Thus, VIP
and SP play important neuroimmunological roles in the pathogenesis of AR.
PMID- 9655217
TI - Expression of intercellular adhesion molecule-1 on the vascular endothelium in
nasal polyps before, during and after topical glucocorticoid treatment.
AB - Nasal polyposis is a result of a chronic inflammatory disorder in the upper
airways. In vitro studies have revealed that extravasation of leucocytes requires
interactions between several sets of adhesion molecules expressed on the
circulating leucocytes and the vascular endothelium. Therefore, the endothelial
expression of intercellular adhesion molecule-1 (ICAM-1) in biopsies from polyps
and inferior turbinates was investigated by the use of immunohistochemical
staining. Biopsies were obtained from 11 patients suffering from nasal polyposis
before, during and after treatment with 100 microg budesonide (Rhinocort
Turbuhaler) in each nostril twice daily. Before, during and after treatment, ICAM
1 was expressed in the majority of vessels in polyps and mucosa of inferior
turbinates. The intensity of endothelial ICAM-1 expression in polyps was
significantly reduced during topical glucocorticoid treatment compared with the
pretreatment and posttreatment levels (p < 0.005). In biopsies from the inferior
turbinates, the intensity of the endothelial ICAM-1 expression was lower during
treatment than after discontinuation of medical treatment (p < 0.005). In
conclusion, topical budesonide treatment seems to downregulate ICAM-1 expression
on the vascular endothelium in nasal polyps. Such an effect may interfere with
leucocyte extravasation and partially account for the anti-inflammatory effect of
local glucocorticoid treatment in human nasal polyposis.
PMID- 9655218
TI - The vomeronasal (Jacobson's) organ in adult humans: frequency of occurrence and
enzymatic study.
AB - The vomeronasal system in adult humans has commonly been regarded as absent or
vestigial, but recently it was found to be more common than previously reported.
In this study, a search for the frequency of occurrence of the vomeronasal organ
(VNO) was performed by examining the nasal septae of 200 adult patients. The
frequency of occurrence was found to vary according to the method of examination.
By anterior rhinoscopy, large pits and even deep grooves lined by glistening
mucosa were visible in 16% of the people examined. Using nasal endoscopes this
ratio increased to 76%. After receiving informed, written consent, from 13
patients undergoing endonasal surgery under general anaesthesia, one VNO was
dissected out. Specimens were examined histologically and histochemically for
succinic dehydrogenase and alkaline phosphatase enzymes. One specimen was
processed for transmission electron microscopy. Two morphologically distinct cell
types were differentiated. One cell type was previously suggested to have some of
the features associated with nerve cells and could have a sensory function. A
possible function for the VNO is postulated.
PMID- 9655219
TI - Evaluation of the vascular reaction in pharyngeal mucosa.
AB - The patency of the upper airways during inspiration is maintained by reflexogenic
muscular dilation, mediated by afferent nerves. Our hypothesis is that a local
disturbance in these nerves might explain the increased tendency of upper airways
to collapse in patients with obstructive sleep apnea. The vascular reaction in
the mucosal microcirculation is regulated by afferent nerves. To investigate
this, we developed the laser Doppler perfusion monitoring method and electrical
nerve stimulation for investigations of the soft palatal mucosa in non-snoring
subjects. A 12 cm probe with integrated bipolar electrodes and a special probe
holder were designed. The bandwidths 12 and 24 kHz were compared and the latter
was better able to detect a high blood-flow. A dose response relation was found
between the voltage stimulation level and percentage increase in blood-flow.
Three series of stimuli (40 V) in 10 subjects caused reproducible vascular
reactions. In conclusion, this method seems to be safe, tolerable and valuable
for investigations of patients with obstructive sleep apnea or other pharyngeal
disorders, e.g. dysphagia, in the search for local nerve lesions.
PMID- 9655220
TI - The free radical forearm flap: a reliable method for reconstruction of the
laryngohypopharynx after in-continuity resection.
AB - Between 1992 and 1996 14 patients with a squamous cell carcinoma of the
laryngohypopharynx underwent tumour resection and primary reconstruction with the
free volar forearm flap. Tumour resection was performed by a head and neck
surgeon and reconstruction by a plastic surgeon. Preoperative radiotherapy was
given to 13 patients and postoperative radiation to one patient. Thirteen
patients were male and one patient was female, with a mean age of 66 years (range
53-79 years). The flap was harvested from the left forearm in 12 cases and from
the right in two. The mean operation time was 12 h (range 11-20 h), and the mean
intraoperative bleeding volume was 700 ml (range 400-1,000 ml). Twelve of 14
flaps survived. One flap was totally lost 3 weeks postoperatively and another was
partially lost 2 weeks after surgery. Overall revisional surgery was carried out
in six patients. Infections and fistulae at the neck occurred in six of the 14
patients. Six of the 14 patients were alive at follow-up. One patient died of an
acute haemorrhage from an oesophageal ulcer 2 months after surgery, one patient
died of a second primary oesophageal cancer and six patients developed
recurrences. The mean survival time was 26 months (range 2-43 months).
PMID- 9655221
TI - Non-radioactive semiquantitative testing for the expression levels of telomerase
activity in head and neck squamous cell carcinomas may be indicative for
biological tumour behaviour.
AB - Head and neck cancer arises and progresses through specific genetic alterations
which lead to an invasive immortal phenotype. The process of immortalization is
associated with the activation of the enzyme telomerase, a ribonucleoprotein with
reverse transcriptase activity which is capable of synthesizing telomeric repeats
at the end of chromosomes. This enzyme is expressed in nearly all neoplasms and
germline cells and is absent in most normal human somatic cells. Because of this
expression pattern testing for telomerase activity may deliver useful diagnostic
and/or prognostic information about clinical tumour behaviour. Telomerase
activity was therefore analysed in 16 primary lesions of head and neck squamous
cell carcinomas (HNSCC) using the polymerase chain reaction-based telomeric
repeat amplification protocol (TRAP). For a sensitive semiquantitative analysis
of telomerase activity TRAP products were mixed with Pico Green I and the
fluorescence emission intensities were measured. All 16 samples tested positive.
When the Pico Green I data were compared with clinical parameters, it was obvious
that N0 necks revealed significantly (p < 0.05) lower emission intensities (i.e.
telomerase activity) than N + necks. Our results indicate that a high telomerase
activity in HNSCC may facilitate lymph node metastasis and that the estimation of
telomerase activity is a useful diagnostic tool which could influence treatment
modalities.
PMID- 9655222
TI - Correlation of epidermal growth factor receptor and radiosensitivity in human
maxillary carcinoma cell lines.
AB - To determine the relationship between epidermal growth factor receptor (EGFR) and
radiosensitivity, we immunostained cells from three maxillary carcinoma cell
lines with an anti-EGFR antibody. The intensity of staining reactivity,
determined by means of an image analysis system, was expressed as grey value (0
black to 255-white). The mean grey values for cell lines IMC-2, IMC-3, and IMC-4
were 181, 210, and 222, respectively, and differed significantly (p < 0.001).
This indicates that IMC-2 had the highest number of EGFR, followed by IMC-3 and
IMC-4. The cells were then irradiated at 1, 2, 4, or 6 Gy, and cell survival was
assessed by means of a standard colony-forming assay. IMC-2 had the highest
survival rates at 1, 2 and 4 Gy, followed by IMC-3 and IMC-4. Therefore, the
survival rates for IMC-2, IMC-3, and IMC-4 after irradiation increased in
proportion to the amount of EGFR in each cell line. These results support the
findings of previous clinical studies which showed that increased expression of
EGFR was associated with higher recurrence rates of glottic and maxillary sinus
carcinoma in patients treated with radiation therapy. The amount of EGFR in cells
may therefore be associated with their radiosensitivity.
PMID- 9655223
TI - Clinical role of p53 and p21WAF1/CIP1 in squamous cell carcinoma of the pyriform
sinus.
AB - To investigate the clinical significance of p53 and p21WAF1/CIP1 in the advanced
squamous cell carcinoma (SCC) of the pyriform sinus, we performed
immunohistochemical staining of p53 and p21WAF1/CIP1 on the biopsy specimens from
patients with stage III or stage IV SCC of the pyriform sinus. The results were
compared with clinico-pathological features, including age, histological grade,
TNM classification, number of neck lymph node metastases on histopathological
examination (pLN) and prognosis. Specific staining for p53 and p21WAF1/CIP1 was
detected in 36% and 32% of the specimens, respectively. Positive staining of
p21WAF1/CIP1 was observed not only in the p53-negative specimens but also in the
p53-positive specimens. Age (p < 0.05) and pLN (p < 0.001) were regarded as the
significant prognostic factors. The 5-year survival rate of the p53-positive
patients (55%) was significantly higher than that of the p53-negative patients
(26.5%: p < 0.03). However, there is no significant difference between the p53
groups after controlling pLN. Although it was not statistically significant, the
5-year survival rate of the p21WAF1/CIP1-positive patients (58.8%) was higher
than that of the p21WAF1/CIP1-negative patients (26.9%). These results suggest
that expressions of p53 and p21WAF1/CIP1 are independent genetic alterations that
may play different roles in the SCC of the pyriform sinus. Expression of p53
could not be regarded as an independent prognostic factor at this point. Further
studies including the molecular biological analysis should be performed in order
to determine the clinical role of p21WAF1/CIP1.
PMID- 9655224
TI - Different KGF expression in squamous cell carcinomas of the head and neck and in
normal mucosa.
AB - Fibroblast growth factors (FGFs) are major factors mediating epithelial
mesenchymal interactions in the epidermis and mucosa. In this study the
expression of the FGFs keratinocyte growth factor (KGF), acidic FGF (aFGF) and
basic FGF (bFGF) was examined in tumour tissue specimens from 14 patients with
advanced-stage squamous cell carcinoma of the head and neck (SCCHN) and 3 SCC
cell lines by reverse-transcribed polymerase chain reaction (RT-PCR) and
immunohistochemistry. None of the SCC cell lines was positive for KGF mRNA,
whereas all cell lines were highly positive for aFGF and bFGF. In SCCHN tissue
samples the level of KGF mRNA expression was significantly lower than in normal
mucosa. Tumour stroma and the submucosal areas of normal mucosa stained intensely
with anti-KGF antibody in immunohistochemical slides, whereas tumour cell nests
were negative. Exposure of SCC cells to KGF thus differs from normal mucosa both
quantitatively and regarding spatial distribution. This fact and the
overexpression of aFGF and bFGF by tumour cells potentially promote tumour
growth, invasion and metastasis. Since these growth factors and their receptors
are well characterized, these observations could lead to new therapeutic
strategies in SCCHN, for instance by blocking their receptors or antisense
targeting.
PMID- 9655225
TI - Microbiology of cervical lymphadenitis in adults.
AB - The microbiology of needle aspirates from 40 inflamed cervical lymph glands was
studied for aerobic and anaerobic bacteria, fungi and mycobacteria. Forty-two
bacterial, 11 mycobacterial and six fungal isolates were isolated. Aerobic
bacteria only were recovered in 11 (27.5%), anaerobes alone in five (12.5%) and
mixed aerobic and anaerobic bacteria in seven (17.5%). Mycobacterium sp. were
recovered in 11 (27.5%) and fungi in six (15%). The recovery of anaerobes was
associated with dental infection. Eighteen aerobic bacteria were isolated and the
predominant ones were Staphylococcus aureus (eight isolates) and group A
streptococci (four). Twenty-four anaerobic bacteria were recovered and the
predominant ones were: Prevotella sp. (six), Peptostreptococcus sp. (five),
Propionibacterium acnes (four) and Fusobacterium sp. (three). These findings
demonstrate the role of anaerobic organisms in cervical lymphadenitis and the
need to culture aspirated material from the glands for both aerobic and anaerobic
microorganisms.
PMID- 9655226
TI - Effects of pre-cues on voluntary and reflexive saccade generation. I. Anti-cues
for pro-saccades.
AB - Experiments on visual attention have employed both physical cues and verbal
instructions to enable subjects to allocate attention at a location that becomes
relevant within a perceptual or motor task some time later (cue lead time, CLT).
In this study we have used valid visual peripheral cues (CLT between 100 and 700
ms) to indicate the direction and location of the next saccade. A cue is
considered valid or invalid if its meaning with respect to the next saccade is
correct or incorrect. A cue is called an anti- or pro-cue if the side of its
presentation is opposite to or the same as the direction of the saccade required
on a given trial. Correspondingly, a saccade is called an anti- or pro-saccade if
it is directed to the side opposite to or the same as the stimulus presentation.
A condition in which the cue and the stimulus are presented on opposite sides
provides a simple way of dissociating voluntary attention allocation from
automatic orienting. This paper considers the anti-cue pro-saccade task: the
subjects were instructed to use the cue to direct attention to the opposite side,
i.e. the location, where on valid trials the saccade target would occur. In the
companion paper we have used the same physical condition, but we have reversed
the instructions as to saccade direction and we have reversed the meaning of the
cue, i.e. we designed a pro-cue anti-saccade task. In this first paper, the
saccadic reaction times (SRTs) of pro-saccades of five adult subjects were
measured in the gap paradigm (fixation point offset precedes target onset by 200
ms). With a CLT of 100 ms, valid anti-cues reduced the number of express saccades
(i.e. saccades with SRTs in the range 80-120 ms) significantly compared with the
control values (no cues). Valid anti-cues with increasingly long CLTs (100-700
ms) resulted in an increasing incidence of anticipatory saccades and saccades
with longer SRTs (more than 120 ms), while the frequency of express saccades
remained below the control value. When cue and saccade target were dissociated in
location or in both location and direction, the effects of the cueing revealed a
much lower spatial selectivity as compared to the effects that have been
described for voluntary attention allocation by means of central cues. The
results suggest that voluntary allocation of attention and cue-induced automatic
orienting not only have different time courses but also have opposite effects on
the generation of express saccades, and different spatial selectivities. A
possible neuronal basis of these results is discussed considering related
findings from electrophysiological studies in monkeys.
PMID- 9655227
TI - Effects of pre-cues on voluntary and reflexive saccade generation. II. Pro-cues
for anti-saccades.
AB - The reaction times of saccades (SRT) to a suddenly presented visual stimulus (pro
saccade) can be decreased and a separate mode of express saccades can occur when
a gap paradigm is used (i.e. fixation-point offset precedes target onset by 200
ms). A valid peripheral cue, presented briefly (100 ms) before target onset, has
been found to facilitate the generation of saccades to the target, thereby
increasing the frequency of express saccades and decreasing the mean latency.
This facilitation occurs only for cues that correctly indicate the direction of
the subsequent target presentation (valid cues). The present study investigates
the effects of valid cues on SRTs and error rate in the anti-saccade task
(saccades in the direction opposite to the stimulus) by systematically varying
the cue lead time (CLT) and using the gap and overlap conditions, i.e. fixation
point remains on throughout the trial. For a CLT of 100 ms, both reaction times
and error rates were significantly increased. With increasing CLT (200-500 ms),
both the reaction times of the anti-saccades and the error rates returned to
approximately control level, with CLT more than 200 ms in both the gap and the
overlap condition. Additional experiments using non-informative cues in the
overlap task showed that the reaction times of correct anti-saccades and the
error rate were decreased when cue and stimulus appeared at the same side.
Analysis of the erratic pro-saccades revealed that almost all of them were
corrected, i.e. they were followed by a second saccade towards the required
location. It is found that the correction times were usually very short, with
intersaccadic intervals between 0 and 150 ms. We suggest that the orienting
mechanism, elicited by a transient peripheral cue, relates to the command and the
decision to make a pro- rather than an anti-saccade. The cue elicits pro
orienting towards its position when a pro-saccade is required, and anti-orienting
when an anti-saccade is required. The orienting effect is transient and decays
with CLTs of more than 200 ms; this result holds for both anti-saccades and pro
saccades. Since subjects reported that they could not prevent the erratic pro
saccades or were often not aware of them, we conclude that this orienting
mechanism occurs automatically, beyond voluntary control.
PMID- 9655228
TI - Comparison of sympathetic sprouting in sensory ganglia in three animal models of
neuropathic pain.
AB - Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after
peripheral nerve injury. Therefore, one possible contributing factor of
sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting
in the DRG after peripheral nerve injury. The present study compared the extent
of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in
three rat neuropathic pain models: (1) the chronic constriction injury model
(CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the
segmental spinal nerve ligation injury model (SSI). All three methods of
peripheral nerve injury produced behavioral signs of ongoing and evoked pain with
some differences in the magnitude of each pain component. The density of
sympathetic fibers in the DRG was significantly higher at all examined
postoperative times than controls in the SSI model, while it was somewhat higher
than controls only at the last examined postoperative time (20 weeks) in the CCI
and PSI models. Therefore, data suggest that, although sympathetic changes in the
DRG may contribute to neuropathic pain syndromes in the SSI model, other
mechanisms seem to be more important in the CCI and PSI models at early times
following peripheral nerve injury.
PMID- 9655229
TI - Short-term changes in neck muscle and eye movement responses following unilateral
vestibular neurectomy in the cat.
AB - The purpose of this study was to investigate changes in neck muscle and eye
movement responses during the early stages of vestibular compensation (first 3
weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG)
activity from antagonist neck extensor (splenius capitis) and flexor (longus
capitis) muscles and eye movements were recorded during sinusoidal visual and/or
otolith vertical linear stimulations in the 0.05-1 Hz frequency range
(corresponding acceleration range 0.003-1.16 g) in the head-fixed alert cat.
Preoperative EMG activity from the splenius and longus capitis muscles showed a
pattern of alternate activation of the antagonist neck muscles in all the cats.
After UVN, two motor strategies were observed. For three of the seven cats, the
temporal activation of the individual neck muscles was the same as that recorded
before UVN. For the other four cats, UVN resulted in a pattern of coactivation of
the flexor and extensor neck muscles because of a phase change of the splenius
capitis. In both subgroups, the response patterns of the antagonist neck muscles
were consistent for each cat independently of the experimental conditions,
throughout the 3 weeks of testing. Cats displaying alternate activation of
antagonist neck muscles showed an enhanced gain of the visually induced neck
responses, particularly in the high range of stimulus frequency, and a gain
decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz)
only. By contrast, for cats with neck muscle coactivation, the gain of the
visually induced neck responses was basically unaffected relative to preoperative
values, whereas otolith-induced neck responses were considerably decreased in the
whole range of stimulation. As concerns oculomotor responses, results in the two
subgroups of cats were similar. The optokinetic responses were not affected by
the vestibular lesion. On the contrary, otolith-induced eye responses showed a
gain reduction and a phase lead. Deficits and short-term changes after UVN of
otolith- and semicircular canal-evoked collic and ocular responses are compared.
PMID- 9655230
TI - Eye movements evoked by proprioceptive stimulation along the body axis in humans.
AB - Proprioceptive input arising from torsional body movements elicits small
reflexive eye movements. The functional relevance of these eye movements is still
unknown so far. We evaluated their slow components as a function of stimulus
frequency and velocity. The horizontal eye movements of seven adult subjects were
recorded using an infrared device, while horizontal rotations were applied at
three segmental levels of the body [i.e., between head and shoulders (neck
stimulus), shoulders and pelvis (trunk stimulus), and pelvis and feet (leg
stimulus)]. The following results were obtained: (1) Sinusoidal leg stimulation
evoked an eye response with the slow component in the direction of the movement
of the feet, while the response to trunk and neck stimulation was oriented in the
opposite direction (i.e., in that of the head). (2) In contrast, the gain
behavior of all three responses was similar, with very low gain at mid- to high
frequencies (tested up to 0.4 Hz) but increasing gain at low frequencies (down to
0.0125 Hz). We show that this gain behavior is mainly due to a gain nonlinearity
for low angular velocities. (3) The responses were compatible with linear
summation when an interaction series was tested in which the leg stimulus was
combined with a vestibular stimulus. (4) There was good correspondence of the
median gain curves when eye responses were compared with psychophysical responses
(perceived body rotation in space; additionally recorded in the interaction
series). However, correlation of gain values on a single-trial basis was poor.
(5) During transient neck stimulation (smoothed position ramp), the neck response
noticeably consisted of two components -- an initial head-directed eye shift
(phasic component) followed by a shift in the opposite direction (compensatory
tonic component). Both leg and neck responses can be described by one simple,
dynamic model. In the model the proprioceptive input is fed into the gaze network
via two pathways which differ in their dynamics and directional sign. The model
simulates either leg or neck responses by selecting an appropriate weight for the
gain of one of the pathways (phasic component). The interaction results can also
be simulated when a vestibular path is added. This model has similarities to one
we recently proposed for human self-motion perception and postural control. A
major difference, though, is that the proprioceptive input to the gaze
stabilizing network is weak (restricted to low velocities), unlike that used for
perception and postural control. We hold that the former undergoes involution
during ontogenesis, as subjects depend on the functionally more appropriate
vestibulo-ocular reflex. Yet, the weak proprioceptive eye responses that remain
may have some functional relevance. Their tonic component tends to stabilize the
eyes by slowly shifting them toward the primary head position relative to the
body support. This applies solely to the earth-horizontal plane in which the
vestibular signal has no static sensitivity.
PMID- 9655231
TI - Influence of hypoglycemic coma on brain water and osmolality.
AB - To study the effects of pronounced hypoglycemia on brain osmolality and brain
edema formation, fasted rats were rendered hypoglycemic by injection of insulin,
and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by
glucose administration. The change in water content in different brain regions
was measured as a change in specific gravity after 30 min of hypoglycemic coma,
or 30, 60, and 180 min after glucose administration. Plasma and brain tissue
osmolality were measured in separate animals. The results show a significant
decrease in specific gravity (increase in water content) in all structures
measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the
period of coma, as well as after 30 min and 60 min of recovery. At 180 min of
recovery, brain water was normalized. The edema affected all structures to the
same degree regardless of their vulnerability to hypoglycemic damage. Brain
tissue osmolality showed a tendency to decrease with decreasing tissue glucose
content. The decrease was significant (P<0.01) at 30 min of isoelectric coma. In
the recovery phase, normal brain osmolality was restored within 30 min.
Measurements of blood-brain barrier (BBB) permeability after 30 min of
hypoglycemic coma showed no extravasation of Evan's blue, though a small but
significant increase in the permeability for aminoisobutyric acid (AIB) in
caudoputamen and in cerebellum was found. To analyze the importance of tissue
acidosis for formation of edema, hypoglycemic animals were made acidotic by
increasing the CO2 concentration in inspired air to produce an arterial plasma pH
of 6.8-6.9. In these animals the edema was of a similar degree to the normocapnic
animals, and the permeability for AIB was normal. We conclude that osmolytic
mechanisms are not the primary cause of the selective neuronal vulnerability in
hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic
insult.
PMID- 9655232
TI - Consistency of unitary shapes in dual lead recordings from myelinated fibres in
human peripheral nerves: evidence for extracellular single-unit recordings in
microneurography.
AB - Percutaneous microneurography is a powerful technique allowing studies of
activity in single nerve fibres of conscious humans. However, the mechanisms by
which single-unit recordings are achieved with this technique are not fully
understood. To further elucidate these mechanisms, dual-lead recordings, using a
modified concentric needle electrode with two separate recording surfaces at the
tip, were performed in normal subjects. Sixty-two single units supplied by large
myelinated afferents were studied. The majority (90%) of the units were recorded
simultaneously on both surfaces but with different action potential amplitudes.
Four types of unitary waveforms were encountered. The potentials recorded on the
two channels were of the same type, although occasionally some details differed.
Parallel waveform changes of the same units occurred simultaneously on the two
surfaces. A displacement of a single fibre from one recording surface to the
other with or without concomitant waveform-type transitions was observed when the
electrode was slightly repositioned intraneurally. The results provided direct
evidence to confirm that concentric needle electrodes record single-unit activity
extracellularly from myelinated nerve fibres, probably at or close to a node of
Ranvier. All the types of action potentials encountered with conventional
tungsten electrodes were also identified in dual-channel recordings with
concentric electrodes, which casts doubt on the previous explanation that single
unit activity recorded with tungsten electrodes is derived from intracellular
sources. Some biological and technical aspects of the findings are discussed,
especially concerning the applicability of in vivo measurements of the time
course of the action potentials in humans and ways to improve microneurography
towards multichannel recordings.
PMID- 9655233
TI - Coordination of two-joint rectus femoris and hamstrings during the swing phase of
human walking and running.
AB - It has been hypothesized previously that because a strong correlation was found
between the difference in electromyographic activity (EMG) of rectus femoris (RF)
and hamstrings (HA; EMG(RF)-EMG(HA)) and the difference in the resultant moments
at the knee and hip (Mk-Mh) during exertion of external forces on the ground by
the leg, input from skin receptors of the foot may play an important role in the
control of the distribution of the resultant moments between the knee and hip by
modulating activation of the two-joint RF and HA. In the present study, we
examined the coordination of RF and HA during the swing phase of walking and
running at different speeds, where activity of foot mechanoreceptors is not
modulated by an external force. Four subjects walked at speeds of 1.8 m/s and 2.7
m/s and ran at speeds of 2.7 m/s and 3.6 m/s on a motor-driven treadmill. Surface
EMG of RF, semimembranosus (SM), and long head of biceps femoris (BF) and
coordinates of the four leg joints were recorded. An inverse dynamics analysis
was used to calculate the resultant moments at the ankle, knee, and hip during
the swing phase. EMG signals were rectified and low-pass filtered to obtain
linear envelopes and then shifted in time to account for electromechanical delay
between EMG and joint moments. During walking and running at all studied speeds,
mean EMG envelope values of RF were statistically (P<0.05) higher in the first
half of the swing (or at hip flexion/knee extension combinations of joint
moments) than in the second half (or at hip extension/knee flexion combinations
of joint moments). Mean EMG values of BF and SM were higher (P<0.05) in the
second half of the swing than in the first half. EMG and joint moment peaks were
substantially higher (P<0.05) in the swing phase of walking at 2.7 m/s than
during the swing phase of running at the same speed. Correlation coefficients
calculated between the differences (EMG(RF)-EMG(HA)) and (Mk-Mh), taken every 1%
of the swing phase, were higher than 0.90 for all speeds of walking and running.
Since the close relationship between EMG and joint moments was obtained in the
absence of an external force applied to the foot, it was suggested that the
observed coordination of RF and HA can be regulated without a stance-specific
modulation of cutaneous afferent input from the foot. The functional role of the
observed coordination of RF and HA was suggested to reduce muscle fatigue.
PMID- 9655234
TI - Differential effects of load stiffness on matching pinch force, finger span, and
effort.
AB - Disparities in load stiffness were used to differentiate and characterize pinch
force, finger-span, and pinch-effort matching in two experiments. All subjects
squeezed a spring-loaded manipulandum in each hand using three-finger pinch.
Subjects in the first experiment were instructed explicitly to match one of the
three continua. Subjects matching force or span were told to attend carefully to
sensations from the hand or arm and to ignore differences in the effort required
to make the sensations equal. They had to achieve and hold a particular target
force with the reference hand and then match force or span with the opposite
hand, usually against a spring with a different stiffness. These subjects were
given as much time as necessary to make their matches and were told which hand
was serving as the reference in each trial. Effort-matching subjects were told to
ignore peripheral sensations and to match effort or motor commands. These
subjects were not told which hand was the reference and were given only 1 s to
make a match, so they made matches by rapidly squeezing both manipulanda
simultaneously and, presumably, with the same voluntary motor command. The
matching behaviors of the three groups were clearly distinguishable and were
consistent with instructions. Results were similar whether different subjects
were assigned different instructions or the same subjects performed all three
match types. In a second experiment, naive subjects were given purposely
ambiguous instructions without reference to a specific continuum and had no time
or accuracy constraints. Subjects produced the same three sensorimotor behaviors
obtained with explicit instructions, showing that the different behaviors were
not artifacts of strict protocols. Taken together, the results show that force,
span, and effort are distinct sensorimotor continua that can be judged reliably.
PMID- 9655235
TI - Hand trajectories of vertical arm movements in one-G and zero-G environments.
Evidence for a central representation of gravitational force.
AB - The purpose of the present experiment was to study the way in which the central
nervous system (CNS), represents gravitational force during vertical arm pointing
movements. Movements in upward (against gravity) and downward (with gravity)
directions, with two different mass loads (hand empty and with a hand-held 0.5-kg
weight) were executed by eight subjects in a normal gravitational environment.
Movements by two cosmonauts, in the two directions, were also tested in a state
of weightlessness. Analyses focused upon finger trajectories in the sagittal
plane. Subjects in a normal gravitational environment showed curved paths for
both directions and weight conditions. In addition, downward movements showed
significantly smaller curvatures than upward movements. Movement times were
approximately the same for all the experimental conditions. Curvature differences
between upward and downward movements persisted during space flight and
immediately postflight. Movement times from both cosmonauts increased slightly
during flight, but returned to normal immediately on reentry in a one-G
environment. Results from the present study provide evidence that gravity is
centrally represented in an anticipatory fashion as a driving force during
vertical arm movement planning.
PMID- 9655236
TI - Calcium metabolism of focal and penumbral tissues in rats subjected to transient
middle cerebral artery occlusion.
AB - The present experiments were undertaken to define changes in tissue calcium
metabolism in focal and perifocal ("penumbral") tissues following 2 h of
transient middle cerebral artery occlusion (MCAO) in rats, induced with an
intraluminal filament occlusion technique. The extracellular calcium
concentration ([Ca2+]e) was measured with ion-selective microelectrodes in
neocortical focus and penumbra. For measurement of total tissue calcium content,
tissue samples from these areas were collected and analyzed with atomic
absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell
from a normal value of about 1.2 mM to values around 0.1 mM, suggesting
translocation of virtually all extracellular calcium to intracellular fluids.
Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however,
[Ca2+]e never returned to normal but stabilized at about 50% of the control value
for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e
showed the expected transient decreases associated with spreading depression-like
(or ischemic) depolarization waves. Recirculation was followed by return of
[Ca2+]e towards normal values. In the focus, water content increased from about
79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of
recirculation, the edema was aggravated (mean values 81.9% and 81.2%,
respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and
83.8%, respectively). In the penumbra, no significant edema was observed until 6
h and 24 h of recirculation. The total tissue calcium content in the focus
(expressed by unit dry weight) increased at the end of the ischemia period
demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the
content increased two- to threefold, compared with control. Changes in the
penumbra were qualitatively similar but less pronounced, and a significant
increase was not observed until after 6 h of recirculation. The results suggest
that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In
focal areas, cells fail to extrude the calcium that is gradually accumulated
during reperfusion and show massive calcium overload after the first 4-6 h of
recirculation. Penumbral tissues show a similar increase in calcium concentration
after 6 h of recirculation.
PMID- 9655237
TI - Characteristics of target-reaching in cats. III. Lifting and protraction with an
obstacle in the movement path and after its removal.
AB - Three cats were trained to perform target-reaching to a horizontal tube with food
placed at shoulder level, and the kinematic characteristics of the movements were
investigated by recording the trajectory of the wrist. From the very onset of
training, a vertical obstacle was placed in front of the cats. The obstacle
forced the animals to perform movements with an initial phase dominated by limb
lifting to position the wrist above the obstacle, followed by a second phase of
protraction towards the tube; in the sagittal plane, the movement paths were
segmented with an upwards convexity. After a training period of 1 year (about
7000 movements), the obstacle was removed. All cats then quickly (within a few
trials) changed the trajectory so that the main part of protraction now occurred
in parallel with limb-lifting during the first half of the movement. The initial
slope of the sagittal movement path became less steep and the upwards convexity
less pronounced. Such trajectories, which predominated for several experiments
after removal of the obstacle, were only slightly different from those observed
in control cats not trained with an obstacle. The results are discussed in
relation to a previously proposed hypothesis of motor "imprinting" during
extensive training in a particular experimental paradigm.
PMID- 9655238
TI - Activation of the ornithine decarboxylase-polyamine system and induction of c-fos
and p53 expression in relation to excitotoxic neuronal apoptosis in normal and
microencephalic rats.
AB - Microencephalic rats obtained by gestational treatment with the DNA alkylating
agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic
neuropathology caused by systemic injections of the convulsant neurotoxin kainic
acid. Taking advantage of this, we have studied in these rats, as well as in
normal rats, the relationship between the induction of cellular signals
supposedly related to cell death and the neuronal apoptosis consequent to kainic
acid administration. While normal rats responded to the excitatory insult with a
large and relatively long lasting increase of the activity of the enzyme
ornithine decarboxylase and of the concentration of putrescine in some brain
regions, these alterations were much smaller in microencephalic rats. Expression
of c-fos in brain regions sensitive to kainic acid was quicker but lasted a
noticeably shorter time in microencephalic rats as compared to normal animals. A
profusion of apoptotic neurons, labeled by an in situ technique, were observed in
the olfactory cortex, amygdala and hippocampus of normal rats injected with
kainic acid, in particular 48 h and 72 h after drug administration. At
corresponding time intervals and with similar topographic localization, neurons
expressing p53 protein were observed. By contrast, microencephalic rats displayed
only in a few cases and in a small number apoptotic neurons in restricted areas
of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases
small populations of p53-expressing neurons were also present in the same areas.
The present observations clearly show that oncogenes such as c-fos and p53, as
well as ornithine decarboxylase which behaves as an immediate-early gene in the
brain under certain circumstances, undergo noticeably lower and/or shorter
induction in microencephalic rats exposed to excitotoxic stimuli. In these rats,
therefore, the cellular signalling pathways studied here and related to
excitotoxic sensitivity and commitment to cell death are downregulated as a
probable consequence of altered brain wiring.
PMID- 9655239
TI - Sensitivity and density of glutamate receptor subtypes in the hippocampal
formation are altered in pentylenetetrazole-kindled rats.
AB - Kindling induced by 13 intraperitoneal injections of 40 mg/kg pentylenetetrazole
(PTZ) over a period of 4 weeks resulted in a significant long-lasting increase in
both the convulsive susceptibility of animals to the convulsant and the density
of the specific [3H]-L-glutamate binding sites in the hippocampus. The
quisqualate- and kainate-sensitive [3H]-L-glutamate binding sites were increased
24 h after the final PTZ injection, whereas the N-methyl-D-aspartate (NMDA)
sensitive sites had only a tendency to be enhanced. Furthermore, we investigated
[3H]-L-glutamate binding on metabotropic receptors and found a significant
increase in the hippocampus following PTZ kindling. In addition, in hippocampal
tissue of kindled rats (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid
(trans-ACPD)-stimulated inositol phosphate formation is increased. It can be
concluded that the increase in metabotropic glutamate receptor (mGluR) density
may be the expression of a specific enhancement in susceptibility of the
glutamatergic systems to this excitatory amino acid developing in the course of
PTZ-induced kindling.
PMID- 9655240
TI - Hemispheric asymmetries and bimanual asynchrony in left- and right-handers.
AB - It is known that, when both forearms are rotated rhythmically and symmetrically,
the dominant hand leads in time by about 25 ms, irrespective of movement speed.
Positron emission tomography was used to test the hypothesis that the asynchrony
results from a functional hemispheric asymmetry. We found that in normal, adult
right-handers portions of the motor and premotor motor areas are more active in
the left than in the right hemisphere. The converse pattern was observed in left
handers. The results suggest that at least some components of the neural
processing involved in bimanual coordination are carried out only in the
hemisphere contralateral to the dominant hand. In particular, between-hands
asynchrony may reflect the time for dispatching pace-setting commands to the
contralateral hemisphere.
PMID- 9655241
TI - The influence of vision on the automatic postural muscle responses of newly
standing and newly walking infants.
AB - In adults, visual inputs do not appear to contribute significantly to automatic
postural muscle responses (90-100 ms latency) activated by transient support
surface displacements causing threats to standing balance, but are activated
through slow pathways with latencies of more than 200 ms. However, it has been
shown that the postural sway behavior of early walking infants is strongly
influenced by visual flow cues that falsely signal self-movement. To determine
whether there also are significant contributions of vision to automatic postural
muscle responses in this age group, two groups of infants were tested on a
moveable platform; pre-walkers (n=6) and early walkers (n=6). Pre-walkers did not
show any measurable effect of visual condition (vision vs no vision) on muscle
response characteristics. However, the integrated gastrocnemius activity of early
walkers increased significantly in vision versus no vision conditions (P<0.05).
These results show that visual cues contribute to, or modulate, the automatic
postural responses in children who are in the developmental transition to
independent walking.
PMID- 9655242
TI - Cloning, characterization, and mapping of human homolog of mouse T-cell death
associated gene.
AB - To establish immunologic autotolerance, self-reactive immature thymocytes are
eliminated by negative selection during T-cell development in the thymus. Self
reactive clones undergo apoptosis after stimulation via the T-cell receptor
(TCR). The process of cell selection is determined by the dedication of the TCR
for tolerogenic antigen/major histocompatibility complex. We have cloned a novel
human gene that is highly homologous in the transmembrane and G protein-coupling
domains to mouse T-cell death-associated gene 8 (TDAG8). The gene, human TDAG8
(hTDAG8), which belongs to the G protein-couple receptor superfamily, encodes a
protein of 337 amino acids. An expressed sequence tag (EST) corresponding to
hTDAG8 was identified from a human thyroid cDNA library and subsequently used to
isolate a full-length genomic clone. Northern blot analysis revealed that the
hTDAG8 gene is expressed predominantly in lymphoid tissues, including peripheral
blood leukocytes, spleen, lymph nodes, and thymus. Stably transfected mammalian
CHO cells were generated, and heterologous expression of hTDAG8 was confirmed by
Northern blot analysis. Fluorescent in situ hybridization (FISH) revealed that
hTDAG8 maps to human chromosome 14q31-32.1, a region in which abnormalities
associated with human T-cell lymphoma or leukemia are found. Taken together,
these data implicate the hTDAG8 gene in T-cell-associated diseases in humans, but
its actual physiological and pathological role in the human immune system needs
further investigation.
PMID- 9655243
TI - Expression of the gene encoding metallothionein-3 in organs of the reproductive
system.
AB - Metallothionein-3 (MT-3) is a new MT gene-family member that inhibits survival of
rat neurons cultured in presence of brain extracts. Contrary to other MT genes,
which are expressed in most tissues and which are highly inducible by metals, MT
3 expression was reported to be mainly in the brain, and it failed to respond to
metals in vivo. We show here that MT-3 mRNA is present in several organs other
than the brain, as assayed by Northern analyses. In the rat, MT-3 mRNA was
detected in the testis, prostate, epididymis, tongue, ovary, uterus, stomach,
heart, and seminal vesicles. The MT-3 mRNA levels in the testis, epididymis,
prostate, and tongue were 22% of those in brain, while in ovary, uterus, and
stomach, they were 4% of the brain level, and they were lower still in the other
organs. The MT-3 gene was not inducible by CdCl2 or lipopolysaccharide in rat
testis and prostate. In the mouse and the human, relative MT-3 mRNA levels were
lower than those found in the rat when compared with those present in brain.
Testicular MT-3 transcript levels remained quite constant during rat postnatal
development in animals aged from 6 to 43 days. In situ hybridization analyses on
human testis sections showed that MT-3 mRNA was present at different levels in
both the Leydig cells and the seminiferous tubules. In orchiectomized rats,
prostatic MT-3 mRNA was decreased by 75%, and injections of dihydrotestosterone
restored MT-3 mRNA levels to control values. Overall, these results show that MT
3 tissue-specific gene expression is broader than previously reported and provide
new experimental systems to study the function and mechanism of action of the MT
3 protein.
PMID- 9655244
TI - Production of recombinant hydroxylated human type III collagen fragment in
Saccharomyces cerevisiae.
AB - A recombinant hydroxylated fragment of human type III collagen has been produced
in Saccharomyces cerevisiae by coordinated coexpression of a collagen gene
fragment together with both the alpha- and beta-subunit genes for prolyl-4
hydroxylase (EC 1.14.11.2). The collagen fragment consisted of 255 residues of
the helical domain and the complete C-telopeptide and C-propeptide domains. It
was inserted under the control of the ethanol-inducible ADH2 promoter in a
multicopy, TRP1-selectable, yeast expression vector, YEpFlag1. The
prolyihydroxylase subunit genes were cloned on either side of a bidirectional
galactose-inducible promoter in a low-copy minichromosome yeast expression
vector, pYEUra3, which is URA3 selectable. Coordinated expression of the three
different gene products after cotransformation into S. cerevisiae was detected by
immunoblotting. Amino acid analysis of an immunoreactive collagen fraction
demonstrated the presence of hydroxyproline, while the presence of a triple
helical domain in the collagen fragment was demonstrated by its resistance to
pepsin proteolysis.
PMID- 9655245
TI - Identification of scaffold/matrix attachment region in recurrent site of
woodchuck hepatitis virus integration.
AB - Scaffold or matrix attachment regions (S/MARs) are noncoding genomic DNA
sequences displaying in vitro selective binding affinity for nuclear scaffold.
They have been reported to be involved in the physical attachment of genomic DNA
to the nuclear scaffold, and thus in the organization of the chromatin in
functional loops or domains, and in the regulation of gene expression. In this
work, we report the identification of an S/MAR in a woodchuck chromosomal locus,
named b3n, previously described as a recurrent site of woodchuck hepatitis virus
(WHV) DNA integration in woodchuck hepatocellular carcinoma (HCC). The 4.3-kb
sequence of this locus contains several Alu-like repeats and a gag-like coding
region with frameshift mutations. Computer analysis revealed the presence of a
region with unusually high AT content, typical of most S/MARs, and of specific
motifs (A boxes, T boxes, topoisomerase II sites, and unwinding elements)
overlapping or in proximity to the region with high AT content, predicting that
b3n might contain an S/MAR. Fragments of the b3n locus were isolated by
conventional and inverse PCR techniques. In in vitro binding experiments with
both heterologous and autologous scaffold preparations, a 592-bp fragment
spanning the region rich in S/MAR features showed marked scaffold affinity, which
was specific when autologous scaffolds were used. The presence of an S/MAR at the
b3n locus and its nature as a recurrent WHV integration site in HCC suggest the
involvement of S/MAR elements in some of the mechanisms leading to liver
oncogenesis.
PMID- 9655246
TI - Linear amplification mapping of polycyclic aromatic hydrocarbon-reactive
sequences in H-ras gene.
AB - Linear amplification, or primer directed single-strand DNA synthesis, is commonly
used in applications such as cycle sequencing and mapping replication block sites
in DNA. Although linear amplification reactions would be expected to synthesize
full-length single-stranded DNA, the synthesis is often prematurely terminated.
We describe the optimization of a linear amplification protocol for synthesizing
a full-length (985-nt) single-stranded pBR322 segment. The enzyme activities of
five DNA polymerases commonly used in PCR amplification, namely, AmpliTaq,
Stoffel fragment, Tth, Pfu, and Vent, were tested either singly or in
combination. The results indicate that the additive action of small amounts of
proofreading DNA polymerases to a nick-translating polymerase is optimum for
linear amplification. From these results, a linear amplification protocol was
developed to map DNA synthesis-blocking sites generated by the reaction of (+/-)
anti-benzo[a]pyrene-7,8-diol-9,10-epoxide, or anti- or syn-dibenzo[a,l]pyrene
9,10-diol-11,12-epoxide with H-ras DNA surrounding the oncogenic codon 61 region.
The results indicate that the central A of H-ras codon 61 (CAA) reacts with these
polycyclic aromatic hydrocarbons.
PMID- 9655247
TI - Effects of bulky polycyclic aromatic hydrocarbon adducts on DNA replication by
exonuclease-deficient T7 and T4 DNA polymerases.
AB - In vitro DNA replication by exonuclease-deficient T7 DNA polymerase (Sequenase)
and an exonuclease deficient T4 DNA polymerase was examined on a 244-nucleotide
DNA template treated with three electrophilic polycyclic aromatic hydrocarbon
(PAH) metabolites: racemic trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10
tetrahydrobenzo[a]pyrene (BaPDE), trans-2,3-dihydroxy-anti-1,10b-epoxy-10b,1,2,3
tetrahydrofluoranthene (FADE), or 3,4-epoxy-3,4-dihydrocyclopenta[cd]pyrene
(CPPE). The DNA replication terminated opposite template guanines and, to a
lesser extent, at template adenines, as expected, as purines were modified
preferentially by the chemical treatments. Analysis of the products synthesized
on the damaged templates indicated that bypass replication by Sequenase proceeded
in three steps: (1) replication first terminated one base 3' to each adduct; (2)
a nucleotide was then incorporated opposite the PAH-modified base; and (3)
replication continued at some sites to give full bypass of the lesions. The rate
of lesion bypass was affected by the type of chemical adduct, the sequence
context of the adduct, and the concentration of deoxynucleoside triphosphates.
Short DNA repeats appeared to facilitate translesion replication.
PMID- 9655248
TI - Characterization of the human Megalin/LRP-2 promoter in vitro and in primary
parathyroid cells.
AB - The gp330/Megalin/LRP-2 protein belongs to the low-density lipoprotein receptor
gene family and is believed to function as an endocytic receptor for the uptake
of lipoproteins and many other ligands. Other functions of this protein may
include a role in calcium sensing in the parathyroid glands and other tissues. In
order to study the transcriptional regulation of the human LRP-2 gene, a clone
containing the 5'-flanking region was isolated from a genomic DNA library, and a
transient transfection protocol for primary bovine parathyroid cells was
established. RNA mapping techniques located the transcriptional start site 136 bp
upstream of the initiation codon. Transient expression in several cell types,
including primary parathyroid cells, and in vitro transcription in HeLa cell
nuclear extracts showed that sequences between -120 and -35 were important for
activated transcription. This region contains consensus binding sites (GC boxes)
for transcription factor Sp1. Mutation of the GC boxes abolished binding of Sp1
in vitro and resulted in reduced transcription in vitro and in transfected cells.
Furthermore, Sp1 stimulated transcription when tethered to the LRP-2 core
promoter through a heterologous DNA-binding domain. Through site-directed
mutagenesis, we identified a novel atypical TATA element with the sequence
TAGAAAA. Intriguingly, this sequence motif was shown previously not to mediate
transcription in a systematic mutational analysis of the TATA motif. Possible
roles of this novel TATA element in the regulation of transcription initiation
are discussed. The isolation and characterization of the LRP-2 promoter and the
5'-flanking region and the establishment of a transient expression assay in
primary parathyroid cells will facilitate studies on the regulatory mechanisms of
the LRP-2 gene and of other genes expressed in the parathyroid glands.
PMID- 9655249
TI - Structural and functional analysis of mouse Msx1 gene promoter: sequence
conservation with human MSX1 promoter points at potential regulatory elements.
AB - Vertebrate Msx genes are related to one of the most divergent homeobox genes of
Drosophila, the muscle segment homeobox (msh) gene, and are expressed in a well
defined pattern at sites of tissue interactions. This pattern of expression is
conserved in vertebrates as diverse as quail, zebrafish, and mouse in a range of
sites including neural crest, appendages, and craniofacial structures. In the
present work, we performed structural and functional analyses in order to
identify potential cis-acting elements that may be regulating Msx1 gene
expression. To this end, a 4.9-kb segment of the 5'-flanking region was sequenced
and analyzed for transcription-factor binding sites. Four regions showing a high
concentration of these sites were identified. Transfection assays with fragments
of regulatory sequences driving the expression of the bacterial lacZ reporter
gene showed that a region of 4 kb upstream of the transcription start site
contains positive and negative elements responsible for controlling gene
expression. Interestingly, a fragment of 130 bp seems to contain the minimal
elements necessary for gene expression, as its removal completely abolishes gene
expression in cultured cells. These results are reinforced by comparison of this
region with the human Msx1 gene promoter, which shows extensive conservation,
including many consensus binding sites, suggesting a regulatory role for them.
PMID- 9655250
TI - Repression of the telomerase catalytic subunit by a gene on human chromosome 3
that induces cellular senescence.
AB - The cellular senescence program is controlled by multiple genetic pathways, one
of which involves the regulation of telomerase and telomere shortening. The
introduction of a normal human chromosome 3 into the human renal cell carcinoma
cell line RCC23 caused repression of telomerase activity, progressive shortening
of telomeres, and restoration of the cellular senescence program. We attributed
the repression of telomerase activity to the marked downregulation of the gene
encoding the catalytic subunit of telomerase (hEST2/hTRT) but not another protein
component (TP1/TLP1) or the RNA component of telomerase. These results suggest
that a senescence-inducing gene on chromosome 3 controls hEST2/hTRT gene
expression either directly or indirectly and support the notion that hEST2/hTRT
is the major determinant of telomerase enzymatic activity in human cells.
PMID- 9655251
TI - Altered expression of epidermal growth factor receptor ligands in tumor promoter
treated mouse epidermis and in primary mouse skin tumors induced by an initiation
promotion protocol.
AB - Multiple epidermal growth factor receptor (EGFr) ligands have been identified,
including transforming growth factor alpha (TGFalpha), heparin-binding epidermal
growth factor (HB-EGF), amphiregulin (AR), and betacellulin (BTC). Previous work
from our laboratory demonstrated that TGFalpha mRNA and protein are upregulated
in epidermis during tumor-promoter treatment of mouse skin and in skin tumors
produced by initiation-promotion regimens. The purpose of the study described
here was to explore the role of other EGFr ligands in multistage skin
carcinogenesis. A single topical treatment of either 12-O-tetradecanoylphorbol-13
acetate (TPA) or chrysarobin or a single full-thickness wound induced the
expression of HB-EGF and AR in mRNA samples isolated from whole mouse skin.
However, only full-thickness wounding significantly elevated expression of the
BTC transcript. The levels of HB-EGF and AR transcripts were significantly
elevated in skin tumors (both papillomas and squamous cell carcinomas) induced by
initiation-promotion protocols. BTC transcript levels were low and barely
detectable in all skin tumors examined. The level of keratinocyte growth factor
(KGF) mRNA was also examined as a possible mechanism for upregulation of EGFr
ligands. Only full-thickness wounding significantly elevated KGF transcript
levels in whole-skin RNA samples. Furthermore, no evidence for upregulation of
KGF mRNA in skin tumors was obtained. The results are discussed in terms of the
role of EGFr activation in skin carcinogenesis and the mechanisms for altered
regulation of EGFr ligands.
PMID- 9655252
TI - Immunological characterization of cell-surface and soluble forms of membrane type
1 matrix metalloproteinase in human breast cancer cells and in fibroblasts.
AB - Membrane type (MT) 1 matrix metalloproteinase (MMP) activates progelatinase A
(pro-MMP-2), a type IV collagenase, on the cell surface of tumors; however, its
function in breast cancer progression and metastasis is not fully understood. To
examine the expression of MT1-MMP in breast cancer cells and fibroblasts, a
specific rabbit antibody (Ab) directed against a unique synthetic peptide derived
from the human MT1-MMP catalytic domain was produced, purified, and
characterized. This Ab is not likely to cross-react with MT2-, MT3-, or MT4-MMP
or any other MMPs. MT1-MMP expression and pro-MMP-2 activation were stimulated by
concanavalin A in two human breast carcinoma cell lines (BT549 and MDA-MB-231)
and in normal human fetal-lung fibroblasts (HFL-1) and were slightly upregulated
by breast cancer cell-fibroblast interactions. Both pro-MT1-MMP in plasma
membrane (63.4 kDa) and the soluble forms of the enzyme in culture medium (57.6
and 25-30 kDa) were detected by immunoblot analysis, suggesting that cell-surface
MT1-MMP exhibits an active conformation without the removal of its propeptide
domain and that the mature enzyme is shed into the medium. In breast cancer
cells, MT1-MMP and a recombinant catalytic domain of MT1-MMP were unable to
activate pro-matrilysin, indicating that MT1-MMP is not a universal activator of
all MMPs. MT1-MMP may play an important role in the invasive growth and spread of
breast cancer cells by specifically activating pro-MMP-2 to cleave the connective
tissue barrier. Furthermore, use of the specific Ab may aid in the investigation
of the role of MT1-MMP in human tumors.
PMID- 9655253
TI - Enhanced expression of anti-apoptotic proteins in human papillomavirus
immortalized and cigarette smoke condensate-transformed human endocervical cells:
correlation with resistance to apoptosis induced by DNA damage.
AB - Apoptosis plays an important role in various biological processes including
embryogenesis, differentiation, homeostasis, and oncogenesis. We have developed a
system composed of primary human endocervical cells (HEN), HEN immortalized by
human papillomavirus (HPV) type 16, and their counterparts subsequently
malignantly transformed by cigarette smoke condensate (CSC). To understand the
role of apoptosis in the multistep oncogenesis of human cervical cells, we
examined the expression of apoptosis-associated proteins in our in vitro model
system. The results showed no significant difference in the levels of apoptosis
inducing proteins bak and bax among all the cell types examined. On the other
hand, the levels of apoptosis-inhibiting proteins bcl-2, bcl-xL and BAG-1
increased progressively after immortalization and transformation. The p53 protein
level decreased in the HPV16-immortalized HEN and increased in one of two lines
of the CSC-transformed HEN. Further, the increased levels of apoptosis-inhibiting
proteins in the HPV16-immortalized and the CSC-transformed HEN correlated with
progressively increased resistance of these cells to apoptosis induced by
staurosporine or cisplatin. This study provided the first evidence that
overexpression of apoptosis-inhibiting proteins is important for both multistep
oncogenesis and resistance of human endocervical cells to apoptosis induced by
DNA-damaging reagents.
PMID- 9655254
TI - Estrogen upregulation of BRCA1 expression with no effect on localization.
AB - Alterations in the expression of the breast and ovarian cancer susceptibility
gene BRCA1 may contribute to the development of mammary and ovarian neoplasia.
The sex-steroid estrogen modulates cell proliferation of normal and neoplastic
breast and ovarian epithelial cells, but the role of estrogen regulation on the
expression of BRCA1 remains to be defined. In this study, estrogen-regulated
BRCA1 expression was examined in breast and ovarian cancer cells. Estrogen
stimulated the proliferation of estrogen receptor (ER)-positive breast MCF-7, C7
MCF-7, and ovarian BG-1 cells as well as the expression of the estrogen-inducible
pS2 gene. This was concomitant with upregulation of BRCA1 mRNA (2.5- to 5.0-fold)
and a 3- to 10-fold induction of BRCA1 protein (230 kDa). Cell fractionation
studies localized the BRCA1 protein to the nucleus in both unstimulated and
estrogen-stimulated cells. The antiestrogen ICI-182780 inhibited estrogen-induced
cell proliferation, BRCA1 mRNA induction, and BRCA1 protein expression in ER
positive cells. Conversely, estrogen did not influence expression of BRCA1 in HBL
100 cells that lacked the estrogen receptor, although the constitutive levels of
BRCA1 mRNA (but not protein) in these cells were 5- to 30-fold higher than in
other breast and ovarian cancer cells. Secretion of the BRCA1 protein into the
cell medium did not account for the discrepancy between the mRNA and protein
levels in HBL-100 cells. Proliferation of HBL-100 cells was not affected by
either estrogen or ICI-182780. Taken together, these data support a role for the
steroid estrogen and the involvement of the estrogen receptor pathway in the
modulation of expression of BRCA1. We therefore propose that stimulation of cell
proliferation may be a prerequisite for upregulation of BRCA1 in breast and
ovarian cancer cells.
PMID- 9655255
TI - Formation of a stable src-AFAP-110 complex through either an amino-terminal or a
carboxy-terminal SH2-binding motif.
AB - The actin-filament-associated protein (AFAP-1 10) forms a stable complex with
activated variants of the Pp60c-src (Src) non-receptor tyrosine kinase through
SH2 and SH3 interactions. In this report, site-directed mutagenesis and a
transient expression system that permits co-expression of activated pp60c-src
(Src527F) and AFAP-110 in Cos-1 cells were used to identify the SH2-binding motif
in AFAP-110. Four tyrosine residues, two in the amino terminus (Y93 and Y94) and
two in the carboxy terminus (Y451 and Y453), were mutated to phenylalanine,
significantly reducing overall steady-state levels of tyrosine phosphorylation
and preventing Src527F from forming a stable complex with AFAP-110. These data
indicate that the major sites for tyrosine phosphorylation are among these four
tyrosine residues and that one or more of these tyrosines may function as an SH2
binding motif. Mutagenesis of just two tyrosines in either the amino terminus
(Y93/Y94) or in the carboxy terminus (Y451/Y453) to phenylalanine had only a
modest effect on steady-state levels of tyrosine phosphorylation and was not
sufficient to abrogate stable-complex formation. These data suggest that Src527F
can form a stable complex with AFAP-110 through either of two independently
functional SH2-binding motifs. Triple-tyrosine mutation demonstrated that Y93 was
not significantly phosphorylated on tyrosine and would not facilitate stable
complex formation, whereas Y94, Y451, and Y453 could be phosphorylated on
tyrosine and would facilitate stable-complex formation. We hypothesize that
Src527F and AFAP-110 interact through a multistep binding mechanism that may
either extend interactions between Src527F and actin filaments or permit
reorientation of Src527F on AFAP-110, which could facilitate the presentation of
Src527F toward other signaling molecules.
PMID- 9655256
TI - Neoplastic phenotype of gap-junctional intercellular communication-deficient WB
rat liver epithelial cells and its reversal by forced expression of connexin 32.
AB - Gap-junctional intercellular communication (GJIC) is involved in cellular growth
control and is often reduced in neoplastic cells. In this study, four GJIC
deficient rat liver epithelial cell lines (WB-aB1, WB-bA2, WB-cD6, and WB-dA2)
were examined for altered growth and tumorigenicity in comparison with their GJIC
competent parental cell line, WB-F344. WB-aB1 cells were also forced to express
connexin 32 (Cx32) by transduction with a Cx32 cDNA retroviral expression vector
to help determine whether the restoration of GJIC could reverse their neoplastic
phenotype. WB-aB1 and WB-bA2 cells had faster population doubling times (PDTs)
and higher saturation densities (SDs) than did WB-F344 cells. In contrast, the
growth of WB-cD6 and WB-dA2 cells was not significantly different from that of WB
F344 cells. WB-aB1 and WB-bA2 cells formed tumors in male F344 rats, but WB-cD6
and WB-dA2 cells did not. After transduction of WB-aB1 cells with Cx32, four
stable clones (WB-a/32-3, -8, -9, and -10) were isolated that had GJIC levels of
5.2%, 44.5%, 69.8%, and 90.5%, respectively. The growth of poorly coupled clones
3 and 8 was similar to that of parental WB-aB1 cells, but the growth of well
coupled clones 9 and 10 was similar to that of WB-F344 cells. The tumorigenicity
of WB-a/32-9 and WB-a/32-10 cells was also significantly lower than that of WB
aB1 cells. Our results suggest that reduced GJIC contributes to neoplastic
transformation of WB cells, that additional changes are necessary, and that
restoration of GJIC by forced Cx32 protein expression can suppress the neoplastic
phenotype of these cells.
PMID- 9655257
TI - Interaction of retinoblastoma protein and D cyclins during cell-growth inhibition
by hexamethylenebisacetamide in TM2H mouse epithelial cells.
AB - To explore the regulation and function of D-type cyclins in breast cancer cells,
the mouse mammary hyperplastic epithelial cell line TM2H was treated with 5 mM
hexamethylenebisacetamide (HMBA), a polar differentiation factor. The resulting
growth-inhibitory effect of HMBA was completely reversible and was analyzed in
terms of percent cells in G1; association of D-type cyclins with cyclin-dependent
kinase (cdk) 4 and cdk6; G1 kinase activity; association of retinoblastoma
protein (pRb) and phosphorylated pRb with D-type cyclins; and association of
p16INK4a, p15INK4b, and p27Kip1 with cdk4 and cdk6. Synchronized TM2H cells were
examined at 0, 3, 5, 9, 12, and 24 h after exposure to 5 mM HMBA. Inhibition of
DNA synthesis, as measured by thymidine uptake, was first observed at 5 h (40%)
and peaked at 24 h (80%). Flow cytometry at 9 h showed treated cells to be in G1
arrest. Western blot analysis showed weakly detectable cyclin D1 but readily
detectable cyclin D2 and D3 proteins at 0 h; thereafter, cyclin D2 and D3 protein
levels remained higher while cyclin D1 levels declined significantly in treated
versus untreated cells. By 5 h (early G1), HMBA had markedly inhibited cdk4 and
cdk6 kinase activity (67% and 75%, respectively) in treated versus untreated
cells. By 9 and 12 h, pRb levels had increased 3.4-fold in treated versus
untreated cells. At 5 h, cyclin D-associated pRb was totally hypophosphorylated
in treated cells and hyperphosphorylated in untreated cells. The levels of pRb
associated with cyclin D2 and D3 increased 2.89-fold and 4.6-fold, respectively,
in treated versus untreated cells. At 5 h, treated cells showed a fivefold
increase in cdk4-associated p27Kip1 and, at 9 h, a fourfold increase in cdk6
associated p27Kip1 over control levels. In confirmation of these data, HMBA was
found to inhibit the growth of Rb-positive Du/145Rb cells but not their Rb
negative parental Du/145 cells. The data suggest that HMBA-induced growth
inhibition is due to multifactorial mechanisms involving decreases in total
cyclin D1 and inhibition of cdk4 and cdk6 kinase activities through elevation of
levels of cdk4- and cdk6-associated p27Kip1 and concomitant increases in
hypophosphorylated pRb and stable cyclin D2/pRb and cyclin D3/pRb complexes that
help maintain pRb in a functional state.
PMID- 9655258
TI - Expression of vascular endothelial growth factor and its receptors in the rat
ventral prostate and Dunning R3327 PAP adenocarcinoma before and after
castration.
AB - BACKGROUND: Angiogenesis is important for prostate organogenesis and prostate
cancer progression. It is not yet known whether androgens promote part of their
control of prostate structure and function by influencing angiogenesis. The aim
of this study was to explore the possible androgenic regulation of the angiogenic
factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk
1/KDR in the rat ventral prostate (VP) and Dunning R3327 PAP adenocarcinoma.
METHODS: RNA was prepared from VP and tumors of intact and castrated rats. VEGF,
flt-1, and flk-1/KDR mRNA levels were determined using competitive RT-PCR.
RESULTS: VEGF121, VEGF165, and VEGF189 together with flt-1 and flk-1/KDR mRNA
were detected. The VEGF, but not flt-1 mRNA levels were significantly decreased
in the VP after castration. The Dunning tumor expressed high levels of mRNA for
VEGF and its receptors compared to the VP. The flt-1 mRNA level in the tumor
increased after castration, while the VEGF mRNA levels were unchanged.
CONCLUSIONS: Decreased mRNA expression of VEGF, but not flt-1, was found in the
rat VP after castration. However, in the Dunning tumor, castration did not alter
the expression of VEGF mRNA. Moreover, elevated levels of both mRNA for VEGF and
its receptors relative to the VP were observed, indicating that the VEGF system
may be important for Dunning tumor development.
PMID- 9655259
TI - Effect of postnecrotic and alcoholic hepatic cirrhosis on development of benign
prostatic hyperplasia.
AB - BACKGROUND: The object of this study was to investigate the effects of hepatic
cirrhosis on the development of benign prostatic hyperplasia and consequent
effects on prostatic volume, serum prostate-specific antigen (PSA), and
prostatism symptoms. METHODS: Sixty patients with postnecrotic cirrhosis and
alcoholic cirrhosis at age 40 and over, and 20 voluntary subjects in the same age
group with normal hepatic functions, were evaluated with prostatic volume
calculation by transrectal ultrasound, symptom scoring according to American
Urology Association (AUA) criteria, measurement of serum prostate-specific
antigen (PSA), serum total testosterone (TT), free testosterone (FT), estradiol
(E2), and calculation of E2/FT ratios, and the results were analyzed
statistically by the Mann-Whitney U-test. RESULTS: Serum FT and TT levels were
significantly lower in the hepatic cirrhosis group compared to the control group
(P = 0.0000 and P = 0000, respectively). Though mean serum E2 level was a little
higher in cirrhotic patients compared to controls, the difference was not
significant; however, the higher E2/FT ratio in the cirrhotic group was
statistically significant (P = 0.27 and P = 0.0002, respectively). In the
cirrhotic group, the decrease in FT and TT levels was greater, as the disease
advanced. While E2 and E2/FT ratio increase, correlate with poor prognosis, no
statistically significant differences were found. Mean prostatic volume, serum
PSA level, and total symptom score were significantly higher in the control
group, compared to the cirrhotic group (P = 0.0001, P = 0.0006, and P = 0.002,
respectively). Prostatic volume decreased parallel to severity of disease in
cirrhotic patients. CONCLUSIONS: The main reason for the decrease in mean
prostatic volume in cirrhotic patients compared to subjects in the same age group
with normal hepatic functions was the decrease in serum FT and TT levels, and the
secondary cause was the increase in E2/FT ratio, indicating estrogenic
predominance.
PMID- 9655260
TI - Expression of the extracellular matrix signaling molecule Cyr61 is downregulated
in prostate cancer.
AB - BACKGROUND: Prostate cancer (CaP) is one of the most common neoplasms in the USA
and Europe. We used differential display PCR (DD-PCR) to identify genes related
to the development of prostate cancer. METHODS: The RNA of 4 patients with
untreated CaP was analyzed for differentially expressed genes. Using DD-PCR, we
identified a downregulated cDNA-fragment in these prostate cancer cells. This
fragment (N7) was cloned and further analyzed by CMRT-PCR, Northern-blot
analysis, and in situ hybridization. RESULTS: Sequence analysis revealed that N7
is identical to the 3'-untranslated region of the recently described immediate
early gene Cyr61. Comparative multiplex RT-PCR with sequence specific primers
showed that Cyr61 is downregulated in the tumor tissue of 7 out of 13 patients.
By in situ hybridization we could demonstrate that the expression of Cyr61 is
restricted to the epithelium of the prostate. Immunohistochemical analysis showed
that Cyr61 protein could be found in the epithelium of normal prostatic tissue,
whereas prostate cancer tissue showed a marked decrease of Cyr61 protein
expression. CONCLUSIONS: Cyr61 is a member of the emerging family of
extracellular signaling proteins and enhances the effect of bFGF. The changed
pattern of expression Cyr61 might therefore contribute to the altered
interactions between epithelial and stromal cells in prostate carcinoma.
PMID- 9655261
TI - Fas-mediated apoptosis in seven human prostate cancer cell lines: correlation
with tumor stage.
AB - BACKGROUND: Apoptosis, or programmed cell death, can be mediated through an
endogenous signaling pathway that emanates from a cell surface receptor known as
Fas. Although best recognized for its role in the immune system, recent studies
have also suggested a role for Fas in mediating apoptosis in the murine prostate.
Little is known, however, regarding the role of Fas-signaling in the human
prostate, and if this signaling pathway is abrogated in the development of
prostate cancer (PC). METHODS: In the current study, seven human PC cell lines
were evaluated for their sensitivities to Fas-mediated apoptosis, using both
morphologic and flow cytometric methods. Fas expression by each cell line was
quantitated by immunofluorescence, and gene expression of three putative
inhibitory molecules was analyzed. RESULTS: The differential sensitivities of the
cell lines to Fas-mediated apoptosis were found to correlate with the clinical
stage of the parental tumors. Specifically, the three most sensitive cell lines
were all derived from primary tumors, while the four most resistant cell lines
were derived from distant metastases. Immunofluorescent analyses of the PC cell
lines revealed that the observed resistance to apoptosis was not due to reduced
expression of membrane-bound Fas. Likewise, this resistance did not correlate
with increased gene expression of the inhibitory molecules FAP-1, ICE epsilon,
and Ich-1S. CONCLUSIONS: Our results using established PC cell lines support
previous studies with prostatic tissue specimens, and suggest that the normal,
differentiated prostatic epithelium, as well as locally invasive PCs, have the
potential to undergo Fas-mediated apoptosis. Conversely, these studies suggest
that metastatic PCs have a reduced apoptotic potential that is mediated by a
novel mechanism.
PMID- 9655262
TI - Establishment of prostatic cell line "Pro9ad" from a p53-deficient mouse.
AB - BACKGROUND: We demonstrated that p53-deficiency is sufficient for immortalization
of fetal uterine cells. In the present study, we further extended our previous
observations to prostate tissues from a young p53-deficient adult mouse. METHODS:
Cell lines were established from the ventral prostate of a p53-deficient male
mouse and maintained in medium containing 10% heat-inactivated fetal calf serum
supplemented with insulin (10 microg/ml), transferrin (10 microg/ml), cholera
toxin (10 ng/ml), and selenium (10(-8) M). RESULTS: Pro9ad, one of the lines
established, exhibits a typical epithelial morphology in culture. Despite the
possession of androgen receptors, the growth of Pro9ad was not stimulated by
5alpha-dihydrotestosterone. Hepatocyte growth factor (HGF) slightly stimulated
proliferation, whereas fibroblast growth factor-1 (FGF-1), keratinocyte growth
factor (KGF), and platelet-derived growth factor AB (PDGF-AB) had no stimulating
effect on growth. However, FGF-2, epidermal growth factor (EGF), and insulin-like
growth factor-1 (IGF-1) accelerated proliferation in a dose-dependent manner. EGF
and IGF-1 additively stimulated growth. CONCLUSIONS: These results suggest that
Pro9ad shares characteristics in common with primary prostatic epithelial cells
despite p53-deficiency, and that p53-deficiency alone allows establishment of
clonal cell lines of the prostate epithelium. Furthermore, the prostates of p53
deficient mice are useful sources for obtaining cell lines.
PMID- 9655263
TI - Stromal and epithelial cells of the canine prostate express parathyroid hormone
related protein, but not the PTH/PTHrP receptor.
AB - BACKGROUND: Parathyroid hormone-related protein (PTHrP), a principal factor in
the pathogenesis of humoral hypercalcemia of malignancy, is also widely expressed
in many normal tissues, including human prostatic epithelial cells. The role of
PTHrP in the prostate is not known, but may include regulation of cell growth and
differentiation or calcium secretion into prostatic fluid. The dog is a valuable
animal model for human prostatic diseases. The objective was to investigate the
expression of PTHrP and the PTH/PTHrP (type 1) receptor in primary cultures of
canine stromal and epithelial prostatic cells. METHODS: Expression and secretion
of PTHrP and the PTH/PTHrP receptor was measured in homogeneous primary cultures
of canine prostatic stromal and epithelial cells using immunohistochemistry,
Northern blots, radioimmunoassay, RT-PCR, and receptor stimulation assays.
RESULTS: Epithelial and stromal cells expressed and secreted abundant PTHrP, but
PTH/PTHrP receptor expression was not detected in either cell type. CONCLUSIONS:
PTHrP expression by stromal and epithelial prostatic cells and the absence of the
PTH/PTHrP (type I) receptor suggest that some functions previously proposed for
PTHrP in the prostate are unlikely. The separation procedure presented is a
valuable tool for studying the role and regulation of PTHrP in the prostate.
PMID- 9655264
TI - Detection of telomerase activity in prostate needle-biopsy samples.
AB - BACKGROUND: Telomerase in an enzyme ribonucleoprotein responsible for cell
immortality and oncogenesis. Telomerase activity has been detected in most
cancers, including prostate cancer. To verify whether the detection of telomerase
in prostate needle biopsy samples could have diagnostic value, we blindly assayed
telomerase activity in samples from patients who were clinically suspected of
having prostate cancer. METHODS: A total of 183 prostate biopsy samples was
obtained from 63 patients who were suspected of having prostate cancer.
Telomerase activity was determined by polymerase chain reaction (PCR)-based
telomeric repeat amplification protocol (TRAP) assay. An internal telomerase
assay standard (ITAS) was used in this study to distinguish false negatives.
RESULTS: Telomerase activity was detected in 17 of 19 (89.5%) patients with
prostate cancer (chi(2) test, P < 0.005). In 39 of 42 (92.9%) biopsy samples from
these 19 prostate cancer patients, confirmed histologically as prostate cancer,
telomerase activity (chi(2) test, P < 0.005) was detected. Meanwhile, we also
found one false-positive sample. In contrast, all of 44 normal or benign prostate
disease patients (124 biopsy specimens) were telomerase-negative. We also
revealed that poorly differentiated prostate cancer often expresses a high level
of telomerase activity. The area of cancer tissue in biopsy specimens was not
associated with relative telomerase activity. CONCLUSIONS: This study suggests
that determination of telomerase activity in prostate needle-biopsy samples might
be a useful tool for detecting prostate cancer.
PMID- 9655265
TI - Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using
antigen-presenting cells pulsed with prostatic acid phosphatase peptide.
AB - BACKGROUND: Most strategies in cancer immunotherapy are aimed at the induction of
a strong cellular immune response against the tumor. Particularly, CD8+ T
lymphocytes have been proven in multiple animal models to be critical for the
eradication of solid tumors. METHODS: We used a population of peripheral blood
derived antigen-presenting cells (APC), containing dendritic cells (DC), to
generate prostate tumor-specific CD8+ T cells. Selected peptides from prostatic
acid phosphatase (PAP), a prostate tissue-specific antigen, were shown to bind
HLA-A2. A high-affinity peptide was used to generate peptide-specific CD8+
cytolytic T lymphocytes (CTL) from the peripheral blood of healthy donors.
RESULTS: The obtained PAP-peptide-specific CTL lysed peptide-coated target cells,
vaccinia-infected target cells, and HLA-A2-positive prostate-tumor cells in vitro
in an antigen-specific manner. CONCLUSIONS: Our results indicate that CTL
precursors to the PAP gene product exist and could be potentially recruited to
elicit an antitumor response. Thus, PAP is a suitable antigen for inclusion in
prostate cancer vaccines.
PMID- 9655266
TI - Family not Faustian values.
PMID- 9655267
TI - An evaluation of the effects of semirigid cervical collars in patients with
severe closed head injury.
AB - The use of a semirigid cervical collar has been recommended to prevent further
cervical spine injury in the management of trauma patients. These cervical
collars are kept on obtunded patients for prolonged periods. We assessed the
incidence of cervical collar related decubiti in patients with severe closed head
injury (SCHI). We also assessed the utility of fluoroscopy in clearing the
cervical spine of patients with SCHI. A retrospective chart review was performed
on 52 consecutive patients with SCHI at a community hospital-based Level II
trauma center over an 8-month period. Thirteen of 34 patients (38%) who survived
>24 hours after admission developed decubiti related to the cervical collar. The
patients who developed decubiti had a significantly greater duration of cervical
collar placement (21.15 +/- 0.99 days) as compared with patients who did not
develop decubiti (4.42 +/- 0.79 days; P = 0.001). Eight patients had their
cervical spine assessed for ligamentous injury by bedside fluoroscopy. All eight
patients had early collar removal; none of these patients developed decubiti.
Patients with SCHI with semirigid cervical collars kept in place for prolonged
periods of time are at risk for developing decubiti. Fluoroscopy in addition to
standard radiographs may "clear" the cervical spine and allow early removal of
these collars.
PMID- 9655268
TI - Autologous closure of giant abdominal wall defects.
AB - Split-thickness skin graft coverage of exposed and granulating intestines within
large abdominal wall defects provides a life-saving permanent biologic dressing.
The resultant abdominal wall defect often is closed with mesh, which may infect
and fistulize. This report describes bilateral advancement flaps of the external
oblique and recti muscles in 11 patients treated over 3 years. The defects, which
averaged 16 x 24 cm, were due to necrotizing fasciitis subsequent to trauma with
bowel perforation (3 patients), multiple ventral herniorrhaphies (2 patients),
perforated diverticulitis (4 patients), and perforated peptic ulcer (2 patients).
Eight patients were initially treated elsewhere where closure was achieved by
split-thickness skin graft in five patients or mesh in 3 patients; 3 developed
enterocutaneous fistulae and were transferred for closure while receiving long
term antibiotic and total parenteral nutrition therapy. All 11 patients had
successful primary closure. The 8 patients operated on electively had primary
healing; 2 developed seromas. Two of the three patients operated on urgently
developed superficial wound infections; both healed by second intent without
compromise of the primary closure. The following conclusions can be drawn: (1)
the linea alba survives despite necrotizing fasciitis, (2) a tension-free primary
closure is feasible; (3) morbidity is minimal, and (4) the long-term result is
excellent.
PMID- 9655269
TI - The changing face of mesenteric infarction.
AB - Intestinal infarction remains a devastating event despite improvements in
clinical recognition as well as diagnostic and therapeutic modalities. Recent
changes in the etiology of this disease have not been examined. A retrospective
review of 121 consecutive patients over a 6-year period was undertaken. Twenty
three patients died without operation, and mortality in the remaining 98 patients
was 50 per cent. The only significant predictor of mortality was an elevated
serum lactate at the time of diagnosis. Thirty-one patients (26%) developed
infarction while hospitalized for another disease process; excluding patients
with obstruction as the etiology of infarction caused this number to rise to 39
per cent. Nonocclusive mesenteric infarction was the most common disease process.
The increased incidence of nonocclusive mesenteric infarction is likely due to
the development of intestinal ischemia in already systemically ill patients.
Nearly half of all cases of intestinal infarction due to nonobstructive causes
develop in already hospitalized patients. The development of unexplained acidosis
in a postoperative or critically ill patient should prompt a search for a
reversible cause of mesenteric ischemia. Intestinal infarction may represent
another example of the multisystem organ failure syndrome.
PMID- 9655270
TI - Role of prophylactic antibiotics for tube thoracostomy in chest trauma.
AB - The objective of this study was to evaluate the efficacy of antibiotic
prophylaxis in association with tube thoracostomy for chest trauma patients with
Injury Severity Scores of 9 or 10. A double-blind randomized clinical trial of
patients requiring tube thoracostomy was performed at an urban Level 1 trauma
center. All patients included in this series were patients with Injury Severity
Scores of 9 or 10 (hemothorax/pneumothorax) who suffered isolated chest trauma
secondary to blunt or penetrating trauma. Before chest tube placement, 139
patients (34 blunt trauma, 105 penetrating trauma) were blindly randomized to
Group A (71 patients) for which they received 1 g cefazolin intravenously every 8
hours or Group B (68 patients) for which they received a placebo intravenously
every 8 hours. Antibiotic or placebo was administered before chest tube insertion
and continued until the time of chest tube removal. The majority of patients
underwent chest tube placement in the emergency room with a small number of
delayed pneumothoraces (4 patients) treated after admission. In the 71 patients
receiving antibiotic, 7 complications (1 pleural effusion, 2 chest tube
reinsertions, 4 additional chest tubes) occurred, none of which were infectious.
In the 68 patients receiving placebo, 7 complications (2 empyemas, 2 pneumonias
with effusions, 1 pleural effusion, 2 chest tube reinsertions) occurred, 4 of
which were infectious and required antibiotic intervention (P = 0.05, Fisher's
exact test). This study showed that patients receiving antibiotics have a
significantly reduced incidence of infectious complications and suggests that
patients who undergo tube thoracostomy for chest trauma would benefit from
administration of prophylactic antibiotics.
PMID- 9655271
TI - Endoscopic retrograde cholangiopancreatography in a general surgery training
program.
AB - Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most complex
procedures performed by endoscopists. ERCP has been performed primarily by
gastroenterologists. There have been no reports in the literature regarding ERCP
training within the framework of a general surgery residency program. The purpose
of this study was to review ERCPs performed by surgical attendings and resident
staff during a 6-year period and compare the success and complication rates with
those found in published gastroenterological series. There were a total of 193
ERCPs performed on 171 patients for a success rate of 82.4 per cent and a
complication rate of 6.7 per cent. A resident was the primary endoscopist in 51
procedures, with 42 (82.4%) successes and 2 complications (3.9%). There were no
significant differences noted between our series and national complication rates,
and between attending and resident procedures (P < 0.05, Chi-square analysis).
This study has shown that surgical endoscopists can perform ERCP with success
rates over 80 per cent, the currently regarded standard of expertise. The
complication rates for these ERCPs were lower than accepted complication rates
cited in current gastroenterological series. The results of this study support
the hypothesis that ERCPs can be performed safely in a surgical residency.
PMID- 9655272
TI - Laser ablation of complex perianal fistulas preserves continence and is a rectum
sparing alternative in Crohn's disease patients.
AB - A 20-year review of the inflammatory bowel disease surgical database of the
author was analyzed for Crohn's disease (CD) patients who had a surgical approach
to perianal fistula disease (PAD). Of 333 patients with CD operated between July
1977 and February 1997, 51 had procedures for PAD (15.3%), and 7 of these
patients had laser ablation of severe, debilitating complex PAD (13.7%). These
patients have traditionally been treated by diverting ileostomy or proctectomy
with permanent diversion. Others have advocated conservative management with long
term antibiotics, staged operations, and insertion of multiple loose setons to
promote drainage. This technique was adapted from the laser procedure now
advocated for severe hydradenitis suppurativa. The hand-held CO2 laser was used
to unroof all fistulas external to the external sphincter. Fistulas were
identified by probing. Infected granulation tissue was removed by laser ablation
until normal fat or muscle was revealed. Intersphincteric abscesses were
unroofed, and a single seton was placed around the external sphincter for all but
submucous fistulas. Patients were usually operated as outpatients with pain
control effected with oral and transnasal agents. A laparoscopically performed
temporary diverting ileostomy was used in one early patient in the series.
Patients were followed, and progress was documented by physical examination and
photographs. Quality of life was assessed. All patients improved remarkably from
their preoperative state. The 4 patients in the group operated more than 1 year
before this review have all demonstrated complete healing. The three more recent
patients are in various stages of healing. Continence was preserved in 7 of 7
patients. No patient has required rectal excision. Recurrence thought to be
related to associated hydradenitis has occurred in 1 patient. Laser ablation is a
valuable technique in the management of patients with severe, debilitating
complex PAD complicating CD. It effectively eradicates the septic tracks and
pockets while preserving sphincter function. It obviates the need for diversion
with or without proctectomy.
PMID- 9655273
TI - Laparoscopic herniorrhaphy in the geriatric population.
AB - Laparoscopy has brought controversy to herniorrhaphy, particularly in the
elderly. We reviewed our experience with this technique in patients older than 65
years at a single teaching institution. Data include demographics, American
Society of Anesthesiologists (ASA) class, operative time, hernia type, type of
repair, hospital stay, and complications. A telephone questionnaire was used to
assess return to normal activity, recurrence, and reason for choosing the
laparoscopic approach. From March 1992 through March 1996, 110 of 328 patients
were eligible. Mean age was 73 +/- 5.6 years; 34 patients had bilateral and 20
had recurrent hernias; 73 patients (66.4%) were ASA-2, and 22 (20%) were ASA-3.
The extra-abdominal and transabdominal preperitoneal approaches were used in 64
and 46 patients, respectively; mean operative time was 87.9 +/- 34 minutes. The
overall complication rate was 15 per cent, with 71 per cent of these being
urinary retention. Patients were discharged the same day (59%) and at 1 day
(33%). Follow-up was available in 84.5 per cent. Recurrence rate was 9.7 per
cent, which was not significantly influenced by complication rate, hernia repair
type, or ASA class. Median return to normal activity was 7 days. ASA
classification correlated with hospital stay (P = .02), but not with
complications, recurrence, or return to normal activities (P = not significant).
Laparoscopic herniorrhaphy appears safe in the elderly.
PMID- 9655274
TI - Bile duct injuries during laparoscopic cholecystectomy: a community's experience.
AB - Reports of bile duct injuries are from tertiary care institutions and, therefore,
may not report the spectrum of management that these patients receive in the care
of these injuries. From June 14,1990 (the first operation) to June 30, 1995, 2654
laparoscopic cholecystectomies (LCs) were reviewed at this community hospital
medical center to determine risk factors contributing to the etiology of these
injuries, time and symptoms at presentation, duration of illness, and management
of these injuries. None of the 13 general surgeons practicing during this time
period had laparoscopic training in a general surgical residency. There were six
major bile duct injuries (0.25%), of which five were available for further
review. All occurred in women with cholelithiasis and chronic cholecystitis. Two
operations were routine and two were associated with biliary tract anomalies. In
two patients, the injuries were detected at LCs and definitive biliary-enteric
anastomoses were performed immediately. Three patients presented at 2, 15, and 42
days after LC. In two patients, one or more operative procedures were performed
before definitive repair and these patients were referred to tertiary care
centers. One patient was managed with sequential CT-guided drainage catheters
after attempted closure of the defect. The length of illness for these five
patients was 8, 69, 348, 402, and 435 days with a follow-up of 245, 345, 531,
575, and 1088 days. Laparoscopic experience before injury by the operating
surgeon was 3, 26, 35, 77, and 333 operations. Major biliary tract injuries
occurred during routine cholecystectomy, length of illness was substantial for
most patients, and biliary-enteric anastomosis was definitive for four of the
five patients. The operating surgeons' "learning curve" did not seem as important
as in other studies.
PMID- 9655275
TI - The changing face of cholecystectomy.
AB - Previous reports in selected patient populations have noted an increase in the
number of cholecystectomies since the introduction of laparoscopic
cholecystectomy. To assess the impact of laparoscopic cholecystectomy in a more
general population, 6473 consecutive cholecystectomies from 7/1/86 to 6/30/95
were reviewed to assess changes in rate of cholecystectomy, diagnosis leading to
cholecystectomy, and general patient demographics. During the 9-year period, the
number of cholecystectomies increased from 618 to 800 per year (29%; P < 0.002).
Even more striking was the redistribution of cholecystectomies performed for
acalculous disease (P < 0.0001), with the rate of increase more than doubling for
each individual diagnosis (biliary dyskinesia, 348%; acute acalculous
cholecystitis, 139%; chronic acalculous cholecystitis, 138%). When comparing
patient characteristics, there was a significant increase in the number of
cholecystectomies performed on females when compared with males. When compared
with other races, whites underwent cholecystectomy for chronic acalculous
cholecystitis at a higher rate (120%; P < 0.0003). The introduction of
laparoscopic cholecystectomy was followed by a dramatic increase in
cholecystectomies performed for acalculous disease and less so for
cholelithiasis. Accompanying the increase were significant alterations in patient
demographics. The study provides indirect evidence for lowering thresholds and
changing indications with reasons for the increases yet to be determined.
PMID- 9655276
TI - Measuring gastroesophageal reflux disease: relationship between the Health
Related Quality of Life score and physiologic parameters.
AB - The Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL)
scale is a reliable, valid, responsive, and practical measure of symptom severity
in patients with GERD. This type of scale is needed to determine effects of
treatments and their comparison. This study defines the relationship between the
GERD-HRQL score and the physiologic parameters of esophagogastroduodenoscopy,
esophageal manometry, and 24-hour esophageal pH monitoring. Fifty-five patients
referred for surgical evaluation of GERD answered the GERD-HRQL, a nine-item
ordinal-scaled questionnaire. They were evaluated with
esophagogastroduodenoscopy, esophageal manometry, and 24-hour pH monitoring. The
relationships among these results were determined by linear regression analysis.
There were no correlations between lower esophageal sphincter (LES) and any of
the pH monitoring parameters (all r < 0.25, P > 0.2), esophagitis grade (r =
0.21, P = 0.2), nor any individual GERD-HRQL item score nor total score (all r <
0.2, P > 0.11). There were correlations between all the pH monitoring parameters
and esophagitis grade (all r > 0.6, P < 0.001), but not with any of the GERD-HRQL
item scores or total score (r < 0.3, P > 0.15). Six of the nine items scores and
the total GERD-HRQL score correlated with esophagitis grade (all r > 0.4, P <
0.01). LES pressure is a poor indicator of symptom severity, the amount of
reflux, and esophageal mucosal damage. pH monitoring-measured reflux and GERD
HRQL-measured symptom severity correlate well with mucosal damage. If the goals
of GERD treatment are to relieve symptoms and reverse mucosal damage, the GERD
HRQL score and 24-hour pH monitoring are better outcome measures than the LES
pressure. In an era of cost containment, the GERD-HRQL may be an adequate outcome
measure.
PMID- 9655277
TI - A prospective experience with selective cholangiography.
AB - A prospective study of patients with symptomatic cholelithiasis was undertaken to
determine the effectiveness of identifying clinically significant
choledocholithiasis with selective cholangiography. Between 1991 and 1995, 262
patients presented to the senior author (K.W.M.) with acute or chronic
cholecystitis. Sixteen patients had a preoperative endoscopic retrograde
cholangiopancreatography (ERCP) for an elevated alkaline phosphatase or total
bilirubin greater than twice the normal value or an ultrasound finding suspecting
choledocholithiasis. Ten of the ERCP patients had choledocholithiasis, with eight
patients having successful clearance by ERCP. Ninety other patients had
intraoperative cholangiography for abnormal serum liver biochemistries, a history
of jaundice or pancreatitis, or a dilated common bile duct (CBD) (>6 mm) on
ultrasound. Fourteen of the intraoperative cholangiography patients and the two
remaining ERCP patients had choledocholithiasis requiring CBD exploration for
clearance of their stones. There were no false-positive cholangiograms, and there
were no bile duct injuries in this series. With 100 per cent follow-up of at
least 2 years, only one patient required ERCP clearance of a retained CBD stone
13 months after cholecystectomy. The positive predictive value and the negative
predictive value for the selective cholangiography criteria are 23 per cent and
99 per cent, respectively. In conclusion, clinically significant
choledocholithiasis can be found effectively with selective cholangiography.
Also, utilizing selective cholangiography reduces the number of routine
cholangiograms by 60 per cent.
PMID- 9655278
TI - The association of intra-abdominal infection and abdominal wound dehiscence.
AB - Concurrent infection is a risk factor for abdominal wound dehiscence. We reviewed
our experience with fascial dehiscence to determine the incidence and to identify
prognostic factors for associated intra-abdominal infection. Over a 7-year
period, 107 patients with abdominal wound dehiscence were identified. Seventeen
were managed nonoperatively, and 90 underwent exploratory laparotomy, 43 of whom
had no intra-abdominal pathology and 47 of whom had intra-abdominal infections.
Demographic factors, comorbid diseases, and potential indicators of systemic
infection did not distinguish patients with intra-abdominal infection from those
without. Patients with an intra-abdominal infection were more likely to have
undergone an emergency operation (74% vs 48%; P < 0.02), an operation on the
colon (55% vs 25%; P < 0.005), or an operation with a higher wound classification
(P < 0.02). Mortality was higher in patients with intra-abdominal infection than
in those without (44% vs 20%; P < 0.02). Wound dehiscence after emergent
operations, and operations with a higher wound classification, especially those
involving the colon, should raise concern for intra-abdominal infection. Thorough
abdominal exploration should be performed at the time of dehiscence repair.
Before nonoperative management is chosen, intra-abdominal infection should be
excluded.
PMID- 9655279
TI - Gamma-probe-guided resection of the sentinel lymph node in breast cancer.
AB - Regional lymph node metastases in patients with breast cancer have fundamental
staging, prognostic, and treatment implications. Classically, axillary lymph node
sampling requires a dissection under general anesthesia. The concept that a
primary, or sentinel, lymph node is the first node to receive drainage from a
tumor has been established in patients with malignant melanomas using
radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1)
radiolabeled sentinel lymph nodes can be identified in most patients with breast
cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts
axillary lymph node metastases in those patients. Patients with operable breast
cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours
preoperatively. Patients underwent gamma probe identification of sentinel lymph
nodes that were biopsied. All patients underwent axillary lymphadenectomy in
conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90
years underwent lumpectomies with axillary dissections (40 patients) or modified
radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of
50 patients (84%). Eight patients (16%) had metastases to the axillary lymph
nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the
axillary nodes. There was one false negative result. A total of 550 lymph nodes
were resected for an average of 11.2 nodes per patient. Sentinel lymph node
scintigraphy and biopsy accurately predicted the axillary lymph node status in 41
of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large
majority of patients. Sentinel lymph node biopsy is an accurate predictor of
axillary lymphatic metastases.
PMID- 9655280
TI - Can scintimammography reduce "unnecessary" biopsies?
AB - 99Tc-sestamibi prone scintimammography (SMM) is a new, noninvasive method of
imaging breast tumors. A pilot study has suggested that SMM increases the
specificity of mammography, and that SMM could be used as an adjunct to
mammography to reduce the number of mammographically indicated biopsies. The goal
of this study was to further evaluate the efficacy of SMM in diagnosing or
excluding breast carcinoma. This was a prospective case series with each patient
serving as her own control. All subjects who had an abnormal mammogram, a
palpable breast mass, or both were eligible for inclusion. All patients underwent
breast examination, conventional mammography, SMM, and breast biopsy. Of the 81
women originally enrolled, 79 women with 80 lesions completed the study. SMM
produced the following results: a sensitivity of 81 per cent, a specificity of 81
per cent, a positive predictive value of 61 per cent, and a negative predictive
value of 92 per cent. These values were significantly lower than the pilot study
results at a power of 80 per cent and P = 0.05. Our results indicate that SMM
does not increase the specificity of conventional mammography and has a low
negative predictive value. We would not recommend it as a screening technique to
avoid biopsy.
PMID- 9655281
TI - Thyroid reoperations: indications and risks.
AB - Thyroid reoperations can be technically difficult and associated with an
increased risk of complications. To determine the indications for reoperations
and the risk of postoperative complications with these procedures, records of 362
patients undergoing thyroidectomy by a single surgeon (R.A.P.) were reviewed.
Thirty-two patients had a reoperation. The group consists of 21 women and 11 men
with an average age of 55 years (range, 31-79). Twenty-four patients had 1 prior
operation, and 8 patients had 2 or more. We performed 4 of the initial
operations, and 28 were done by surgeons at other centers. Fourteen reoperations
were done for symptomatic multinodular goiter (MNG), and 5 because of a change in
the histologic diagnosis from benign to cancerous. The remainder were for further
treatment of malignancy. The most common operation was completion thyroidectomy
(31). In 3 patients, either unilateral or bilateral modified radical neck
exploration was performed. One patient required median sternotomy. One subtotal
thyroidectomy was also performed. Recurrent laryngeal nerve injury occurred in 2
patients. It resolved in 1 patient but was permanent in another, who had 3
operations for MNG. One of the 2 patients with preoperative unilateral vocal cord
paralysis had return of function after removal of a substernal goiter. The other
had a permanent nerve injury from the original surgery. Three patients had
postoperative hypocalcemia (calcium <8.0 mg/dL). This resolved in all patients
within 1 to 6 months. One patient who had a third operation for MNG had
postoperative hemorrhage necessitating tracheostomy for airway control. Another
patient developed a seroma that resolved within 2 months. We conclude that
reoperations are indicated for both benign and malignant thyroid disease. Because
they carry a higher risk of complications, every effort should be made to avoid
them by performing definitive initial treatment.
PMID- 9655282
TI - Inadequate documentation and resection for gastric cancer in the United States: a
preliminary report.
AB - Patients entered into Southwest Oncology Group gastric adjuvant protocol INT 0016
(SWOG 9008) after a "curative" gastric resection were assessed to determine
practice patterns of more than 300 surgeons nationwide who performed "curative"
gastric resections for 453 gastric cancer patients. The most common gastric
resection performed was distal in 256 patients, proximal in 118, and total in 79.
Extragastric organs resected were omentum (285), spleen (59), pancreas (18), and
bowel (17). The extent of lymphadenectomy as staged by Japanese rules was 246
(54.2%) D0 resections, 173 (38.1%) D1 resections, 28 (6.2%) D2 resections, and 7
(1.5%) D3 resections. Staging of the cancer was poorly documented, with no
statement made regarding the status of the primary cancer in 6 per cent, liver in
10 per cent, lymph nodes in 17 per cent, and omentum in 17 per cent. The greater
the lymph node clearance, the greater the chance of resecting to a level of
negative lymphatics, given that 45 per cent of nodes were involved when 10 or
less were removed, whereas only 17 per cent were positive when more than 40 were
cleared. The lack of adequate clearance of lymph nodes and poor documentation of
tumor stage suggests that a more regimented surgical approach to this uncommon
cancer is required.
PMID- 9655283
TI - Preoperative versus postoperative chemoradiation for patients with resected
pancreatic adenocarcinoma.
AB - Two groups of patients with adenocarcinoma of the pancreas treated with either
preoperative chemoradiation (preop CTRT) or postoperative chemoradiation (postop
CTRT) were retrospectively analyzed for various treatment-related parameters.
Between November 1986 and October 1996, a total of 70 patients with pancreatic
adenocarcinoma were enrolled into preop CTRT protocols at our institution. Twenty
five patients with adenocarcinoma of the head of the pancreas underwent
pancreaticoduodenectomy with curative intent. After the closure of the preop CTRT
protocols, we had the opportunity to perform 23 pancreatic resections without
preop CTRT. After surgery, these patients were advised to undergo CTRT. These two
groups of patients were therefore selected consecutively, dependent only on the
time of referral and no other bias. These two cohorts of patients are compared
for various intraoperative parameters, length of hospital stay, pathologic
findings, time to recurrence, and survival. Mean age was 65 and 66 years in the
preop and postop CTRT groups, respectively. Sex distribution was almost equal.
Treatment breaks resulting in greater than 1 week delay in the radiotherapy
occurred in 2 (8%) of 25 patients in the preop CTRT group (myelotoxicity in 1
case and biliary sepsis in 1 case), whereas no treatment breaks >1 week occurred
in those receiving postop CTRT. Eleven patients in preop CTRT had grade 3 or 4
toxicity, whereas none was noted in those with postop CTRT. There was one
postoperative death in the preop CTRT group and none in the postop CTRT group.
Mean time to the start of CTRT was 45 days (range, 20-66 days) after
pancreaticoduodenectomy. Delay of >60 days to the onset of CTRT occurred in 2
(22%) patients and was attributable to patient delays in time to recover from
surgery or patient noncompliance. Furthermore, 5 of 23 patients (22%) in the
postop CTRT group did not receive treatment for various reasons. Average
estimated operative blood loss was 1933 mL (median 1550) and 1060 mL (median
1000) for preop and postop CTRT groups, respectively. Mean length of operation
was 488 minutes (median 480) and 486 minutes (median 480). Median length of
postoperative stay was 22 and 20 days (ranges, 9-144 and 10-38). Pathological
findings in the resected specimens showed significantly fewer involved nodes in
the preop CTRT group (28 vs 87%; P = 0.0006), whereas similar numbers of
nodes/patient were counted in each group (14 vs 22, P = 0.11). More negative
resection margins were observed in the preop CTRT group (28 vs 56%; P = not
significant). A significantly greater amount of fibrosis replacing the tumor was
observed in the preop CTRT group (70 vs 40%; P = 0.0001). There were no
significant survival differences observed (median 20 months vs 25 months; P =
0.48), in follow-up that ranged from 4 to 76 months (median 44 months for
surviving patients) for the preop group and 4 to 40 months (median 16 months for
surviving patients) for those with postop CTRT. Local failure either alone or as
a component of distant failure occurred in 16 per cent (4 of 25 patients) with
preop CTRT and 16.6 per cent (3 of 18) with postop CTRT. Analysis of differences
between those treated with preoperative and postoperative CTRT demonstrates
similarity in toxicity and effects. However, 22 per cent of patients intended for
postoperative therapy did not receive treatment.
PMID- 9655284
TI - Unilateral parathyroid exploration.
AB - Unilateral neck exploration (UNE) for primary hyperparathyroidism can be done
with the same excellent results as bilateral neck exploration (BNE) with
decreased operative time and postoperative complications with a good preoperative
localization study. One hundred six charts were reviewed retrospectively in
patients operated on between May 1989 and October 1996 with primary
hyperparathyroidism. Seventy-seven of these patients had preoperative ultrasounds
(US) performed by a radiologist interested in parathyroid ultrasonography. UNE
was performed if the operative findings were consistent with the US and a normal
gland was identified on the same side. If a normal gland was not identified on
the initial side or there was a question of hyperplasia a BNE was performed.
Forty-six of the 77 patients had UNE, and 31 had BNE. Sixty-nine of these
patients were found to have accurate US. Based on these results there is a 90 per
cent accuracy rate for US performed by an interested radiologist. Comparing
operative times between patients with UNE and BNE, there was a statistical
difference (P = 0.001). Complications were also recorded in each group. Patients
with UNE had a 22 per cent complication rate, whereas patients with BNE had a 45
per cent complication rate. This difference was statistically significant (P =
0.04) (Fisher's exact test). The majority of complications were asymptomatic and
symptomatic hypocalcemia. Two patients in the BNE group experienced transient
hoarseness. The advantages of UNE include reduced morbidity, decreased operative
time and avoidance of scarring in the contralateral neck. In the total study
population (n = 106), 99 patients (93.4%) had a single adenoma. An accurate,
noninvasive, low-cost preoperative localization study is necessary to practice
UNE for primary hyperparathyroidism. Parathyroid US, done by an interested
radiologist, with a 90 per cent accuracy rate, meets all these criteria.
PMID- 9655285
TI - Clinical pathways for general surgeons: elective colectomy for recurrent acute
diverticulitis.
PMID- 9655286
TI - Progress in endocrine therapy for breast carcinoma.
PMID- 9655287
TI - p53 sequence analysis predicts treatment response and outcome of patients with
esophageal carcinoma.
AB - BACKGROUND: The ability to predict biologic behavior and treatment responsiveness
would be a valuable asset in the multimodality approach to esophageal carcinoma.
The authors examined whether alterations of the p53 gene correlate with
clinicopathologic parameters, response to preoperative chemotherapy/radiotherapy,
and outcome in patients with esophageal carcinoma. METHODS.
Histopathologic/genetic analysis of p53 was performed on formalin fixed, paraffin
embedded tissues. Tissue sections were stained immunohistochemically for p53
protein followed by topographic genotyping comprised of polymerase chain reaction
amplification and direct sequencing of p53 exons 5-8. All patients received
induction chemotherapy (5-fluorouracil, cisplatin, and alpha-interferon) and
concurrent external beam radiotherapy (4500 centigrays) followed by resection.
RESULTS: p53 analysis performed on 42 tumors from patients with potentially
resectable esophageal carcinoma revealed 25 of the 42 tumors (59.5%) to be p53
immunopositive; however, only 17 of the 42 tumors (40.5%) were proven to contain
p53 point mutational damage in exons 8 (n=5), 5 (n=5), 7 (n=4), and 6 (n=3).
Eight cases were weakly immunopositive and had no genotype mutation suggesting
hyperexpression of normal wild-type p53. Genotyping also identified two
immunonegative cases with deletion-type mutations (exons 5 and 6). Tissue samples
collected before and after chemotherapy/radiotherapy exhibited fidelity in p53
mutational genotype in all cases. The presence of a p53 point mutation positively
correlated with pTNM stage (P=0.003) and residual disease in the resected
specimen (P=0.01). Moreover, survival of patients with p53 mutations was
significantly lower than that of patients without mutations (overall survival of
21.6 months vs. 40 months; P=0.0038; and disease free survival of 14.1 months vs.
38 months; P=0.0004). CONCLUSIONS: Histopathologic/genetic analysis is a better
determinant of p53 mutational damage than immunohistochemistry alone and can be
used as a prognostic marker for esophageal carcinoma. p53 genotyping may define a
subset of patients who respond to chemotherapy/radiotherapy and may predict who
potentially benefits from multimodality therapy.
PMID- 9655288
TI - Changes in tumor marker levels as a predictor of chemotherapeutic effect in
patients with gastric carcinoma.
AB - BACKGROUND: Evaluating chemotherapeutic effect in patients with gastric carcinoma
sometimes is difficult. The authors investigated whether changes in the serum
levels of three tumor markers can be used to predict the clinical outcome after
chemotherapy. METHODS: Thirty patients with advanced and recurrent gastric
carcinoma were treated with continuous 5-fluorouracil and low dose cisplatin for
4 weeks. Thirteen patients were treated neoadjuvantly prior to gastrectomy. The
serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl
Tn antigen were measured prior to and after chemotherapy. Responders were defined
as those in whom abnormal serum levels of all three markers decreased to at least
50% of the pretreatment values and remained stable for at least 1 month. RESULTS:
The tumor markers could be evaluated in 27 of 30 patients (90%). The median
duration of survival for the 15 responders and 12 nonresponders was 17 months and
6 months, respectively. There was a significant difference in the median duration
of survival between the responders and nonresponders using the log rank test
(P=0.0005). In the patients who received neoadjuvant therapy, the eight
responders had a significantly longer survival period than did the three
nonresponders (P=0.018). Seven of the eight responders showed evidence of tumor
destruction histologically whereas none of the three nonresponders did.
CONCLUSIONS: Changes in the serum levels of these tumor markers after
chemotherapy may be an excellent prognostic indicator for patients with gastric
carcinoma.
PMID- 9655289
TI - Unique features of gastric carcinoma in the young: a population-based analysis.
AB - BACKGROUND: It is suspected that young patients with adenocarcinoma have a more
aggressive form of disease and therefore a poorer prognosis than older patients.
METHODS: A retrospective cohort study used the population-based tumor registries
of Orange, San Diego, and Imperial Counties. Cases (patients age < or =40 years
with gastric carcinoma) were compared with controls (patients age >40 years with
gastric carcinoma). RESULTS: The overall, age-adjusted incidence rate of gastric
carcinoma was 10.2/100,000. Approximately 5.5% of 3,020 cases occurred in
patients age <41 years. Young patients (especially whites and Latinos) were more
likely to have distant metastases [45% versus 34%; odds ratio (OR)=2.6; 95%
confidence interval (CI), 1.4-4.8; P < 0.001]. The histology of young patients
(especially Latinos and Asians) was more likely to be signet ring cell (28%
versus 15%; OR=2.3; 95% CI, 1.6-3.3; P < 0.001), and the grade of young patients
(especially whites and Latinos) was more likely to be Grade 3 or 4 (according to
the World Health Organization International Classification of Diseases for
Oncology; 68% versus 56%; OR=2.1; 95% CI, 1.4-3.3; P < 0.001). The tumors of
young patients (especially Asians) were less likely to be of the gastroesophageal
junction (16% versus 27%; OR=0.47; 95% CI, 0.31-0.72; P < 0.001) and of the
antrum (17% versus 22%; OR=0.62; 95% CI, 0.41-0.95; P=0.03) than the gastric
body. Younger patients were more likely to receive chemotherapy (50% versus 28%;
OR=2.7; 95% CI, 1.9-3.7; P < 0.001). Only patients age >70 years had an
independent increased risk of dying from all causes in comparison with young
patients (relative risk 1.46; P=0.01). CONCLUSIONS: Young gastric carcinoma
patients have adverse clinical and pathologic features in comparison with older
patients. In this study, young age was not found to be an independent predictor
of overall survival.
PMID- 9655290
TI - GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor
prognosis.
AB - BACKGROUND: Malignant cells exhibit increased glycolytic metabolism, and in many
cases increased glucose transporter gene expression. The authors hypothesized
that GLUT1 glucose transporter expression is increased in colorectal carcinoma,
and that the degree of expression might have prognostic significance. METHODS:
GLUT1 glucose transporter immunostaining was studied in normal colon and benign
colon adenomas and in 112 colorectal carcinomas from patients for whom long term
clinical outcome was known. RESULTS: GLUT1 immunostaining was absent in normal
colorectal epithelium and tubular adenomas, and absent or only weakly apparent in
tubulovillous adenomas. The majority of carcinomas (101 of 112; 90%) had GLUT1
immunostaining. Tumors from 92 patients had low GLUT1 expression (< 50% of cells
were GLUT1 positive) and 19 of these patients (21%) died of disease during follow
up. In contrast, tumors from 20 patients had high GLUT1 expression (> 50% of
cells were GLUT1 positive) and 9 of these patients (45%) died of disease during
follow-up. Disease specific mortality was greater in patients with high GLUT1
tumors (relative risk of 2.4; P=0.02). In a multivariate analysis to assess
whether high GLUT1 staining correlated with increased mortality independently of
Dukes stage, the risk of death from colon carcinoma in the group with high GLUT1
staining was 2.3 times that in the group with low GLUT1 staining, a difference
that approached statistical significance (P=0.07). CONCLUSIONS: GLUT1 glucose
transporter expression is associated strongly with neoplastic progression in the
colon, and assessment of the extent of GLUT1 immunostaining in colorectal
carcinoma identifies patients with a poorer prognosis.
PMID- 9655291
TI - Increased levels of phosphatidylinositol 3-kinase activity in colorectal tumors.
AB - BACKGROUND: Phosphatidylinositol 3-kinase (PI 3-kinase), an enzyme that
phosphorylates inositol phospholipids at the D-3 position of the inositol ring,
has been implicated in the signaling pathways regulating cell growth by virtue of
its activation in response to various mitogenic stimuli. In spite of the
considerable attention PI 3-kinase has received with regard to its possible role
in the mitogenic pathways in hematopoietic malignancies, there are few reports of
investigations into PI 3-kinase activity in solid tumors. METHODS: Colorectal
tumor tissue and normal-appearing colonic mucosa from the same patients were
homogenized and solubilized and adjusted to equal protein levels. PI 3-kinase
then was immunoprecipitated from 200 microg of the solubilized tissue using a
polyclonal antibody to the p85 subunit of PI 3-kinase. PI 3-kinase activity was
assessed using phosphatidylinositol as the substrate and the assay product
analyzed by thin-layer chromatography. Phosphorylation of phosphatidylinositol in
the D-3 position was confirmed by high performance liquid chromatography analysis
of deacylated and deglycerated products. RESULTS: Thirty-two of the 37 tumors
tested (86%) demonstrated increased PI 3-kinase activity compared with normal
appearing mucosa from the same patients (overall mean increase+/-standard error
of the mean=3.8+/-0.6-fold; P < 0.05, Student's t test for paired data). The
frequency and extent of increased PI 3-kinase enzyme activity in tumors did not
correlate with clinical parameters or the presence of oncogenic ras mutations.
CONCLUSIONS: In this study colorectal tumors exhibited enhanced PI 3-kinase
activity compared with normal colonic mucosa, raising the possibility that PI 3
kinase may be a potential target for new strategies for the treatment of
colorectal carcinoma.
PMID- 9655292
TI - Long term results of single session percutaneous ethanol injection in patients
with large hepatocellular carcinoma.
AB - BACKGROUND: The objective of this study was to evaluate the indications for
percutaneous ethanol injection (PEI) performed in a single session under general
anesthesia for treating patients with cirrhosis and large (tumors > 5 cm)
hepatocellular carcinoma (HCC), and relevant survival curves. METHODS: Between
November 1991 and November 1996, 108 patients were treated (a total of 128
procedures). They fell into 3 groups: 24 patients with single, encapsulated HCC
measuring from 5-8.5 cm (Group A); 63 patients with single, infiltrating HCC
measuring from 5-10 cm or multiple HCC (Group B); and 21 patients with advanced
disease, either hepatic (Child's Class C) or neoplastic (symptomatic HCC or with
portal thrombosis) type (Group C). The mean amount of ethanol injected was 62 mL.
The average hospital stay was 3.8 days. The mean follow-up time was 40 months.
RESULTS: The 1-, 2-, 3-, and 4-year survival rates were: 72%, 65%, 57%, and 44%,
respectively, for Group A; 73%, 60%, 42%, and 18%, respectively, for Group B; and
46%, 25%, and 0%, respectively, for Group C. Mortality was 0.7% (bleeding from
esophageal varices in a Child's Class C patient). The rate of major complications
was 4.6% (1 case of peritoneal hemorrhage, 1 case of severe liver failure, 1 case
of transient renal insufficiency, 1 case of peritoneal seeding, and 2 cases of
infarctions of a segment adjacent to the tumor). CONCLUSIONS: Single session PEI
has been proven to be a valid alternative in patients otherwise treated
surgically or with transcatheter arterial chemoembolization who present with
adverse prognostic factors or risks for these therapies, and may be an option for
selected patients with advanced disease previously excluded from any therapy.
Risk conditions are marked portal or pulmonary hypertension or esophageal varices
at risk of bleeding, superficial tumors with severe coagulation disorders,
hyperfibrinolysis, chronic renal insufficiency, and obstructive jaundice.
PMID- 9655293
TI - Natural killer cell activity in patients with hepatocellular carcinoma: a new
prognostic indicator after hepatectomy.
AB - BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is
believed to play an important role in host anticancer defense mechanisms. The aim
of this study was to examine the prognostic significance of NK cell activity
after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell
activity in 210 patients with hepatocellular carcinoma was measured and evaluated
in relation to clinicopathologic variables using univariate and multivariate
analyses. RESULTS: The NK cell activity was decreased significantly in
hepatocellular carcinoma patients compared with the control groups (P < 0.001).
No correlation was observed between NK cell activity and the clinicopathologic
variables. Multivariate analyses indicated that NK cell activity as well as
intrahepatic metastases, platelet count, and serum albumin level were independent
prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK
cell activity will help predict recurrence and prognosis after hepatectomy in
patients with hepatocellular carcinoma.
PMID- 9655295
TI - Quality of life and psychosocial adjustment of young patients after treatment of
bone cancer.
AB - BACKGROUND: The aim of this study was to collect information about the
psychosocial situation of young patients after multimodality therapy for bone
cancer. METHODS: Selection criteria for patients were ages 15-30 years, tumor
localization at the extremities, and an interval of at least 1 year since the end
of treatment. Of 110 patients, 60 were willing to participate. Evaluation of
psychosocial quality of life included assessment of psychosocial adjustment and
age-appropriate achievements as well as identification of problems typical for
this patient group. RESULTS: Approximately 80% of patients revealed, at the very
most, only minor psychosocial problems. They were able to adapt well to their new
living conditions, although strong efforts were necessary for them to deal with
problems such as restricted mobility, catching up with school, or changing jobs
or job orientation. Differences between patients and control subjects emerged in
the areas of marital status, independent living, and parenthood. The most
recently determined levels of education and income were similar. Neither clinical
data nor physical or functional sequelae affected psychosocial adjustment, with
one exception: patients diagnosed in adolescence had significantly more problems,
especially in the area of social well-being, than patients diagnosed in childhood
or early adulthood. CONCLUSIONS: Given the limitations of this study, the
findings suggest that survivors of bone cancer are not necessarily at risk of
developing long term emotional or social problems and are not precluded from
leading active and independent lives.
PMID- 9655294
TI - Technetium-99m methoxyisobutylisonitrile chest imaging of small cell lung
carcinoma: relation to patient prognosis and chemotherapy response--a preliminary
report.
AB - BACKGROUND: The purpose of this preliminary study was to evaluate retrospectively
the relation between chemotherapy response and survival time, using technetium
99m methoxyisobutylisonitrile (Tc-99m MIBI) uptake in small cell lung carcinoma
(SCLC) to detect the expression of multidrug resistance (mdr)-mediated 170-kDa P
glycoprotein (PgP). METHODS: Before the administration of chemotherapy (which
consisted of cisplatin 25 mg and etoposide 125 mg every day per 3-day course), 15
male patients (ages 54-64 years) with SCLC were enrolled in this study to undergo
Tc-99m MIBI chest imaging, including single photon emission computed tomography
(SPECT) and planar imaging, for qualitative and quantitative assessments of PgP
in their SCLC. RESULTS: In 12 of 15 cases (80%), SCLC could be detected by visual
interpretation of the Tc-99m MIBI chest SPECT images. In 13 of 15 cases (87%), Tc
99m MIBI chest SPECT images (either positive SPECT with good response or negative
SPECT with poor response) correctly predicted chemotherapy response. The
correlation between tumor uptake ratios obtained by planar images (total counts
in the region of interest [ROI] of the tumor divided by total counts in the same
size ROI of the contralateral normal lung) and survival days (from the time of
SCLC diagnosis to the time of the patient's death) was both positive and good
(correlation coefficient=0.83). CONCLUSIONS: Tc-99m MIBI chest images have the
potential to demonstrate mdr-PgP expression in SCLC and to predict patient
prognosis and chemotherapy response.
PMID- 9655296
TI - Survival of premenopausal women with breast carcinoma: effects of menstrual
timing of surgery.
AB - BACKGROUND: It is controversial whether the timing of tumor excision relative to
the menstrual cycle influences the survival of patients with breast carcinoma.
METHODS: Premenopausal patients (n=614) who had surgery for invasive,
nonmetastatic breast carcinoma during the period 1978-1988 participated in an
epidemiologic survey, reporting their menstrual cycle length and the date of
their last menses. We ascertained deaths from any cause before 1993. RESULTS:
Using Cox modeling, we found a nonlinear variation in the relative risk (RR) of
death according to the timing of surgery during the menstrual cycle. The curve
was best described by a cosine transformation of a 28-day cycle. For patients who
had breast carcinoma surgery on the estimated day of ovulation, the risk of death
was 0.59 (95% confidence limits [CLI=0.39-0.89, P=0.013) compared with patients
who had surgery at the approximate time of menses. We observed this for patients
treated in 1978-1981 (RR=0.43, 95% CL=0.23-0.83, P=0.011) and 1982-1983 (0.25,
95% CL=0.10-0.63, P=0.003), but not in 1984-1988 (1.48, 95% CL=0.64-3.4). The
difference observed for 1984-1988 was explained by a significant improvement in
the mortality rate (P=0.0004) for women whose surgery took place during menses or
near to the date predicted for the next menses. No such improvement for women who
underwent breast carcinoma surgery around the time of ovulation was observed
during the period 1984-1988. These changes were not explained by the performance
of lumpectomy or the increasing interval between biopsy and tumor excision.
CONCLUSIONS: The shape of the survival curve contradicted the idea that it could
be explained by levels of circulating estradiol or progesterone. Because
observations that surgery was affected by menstrual timing seem not to have
persisted beyond the mid-1980s, this study should not be used to support
recommendations that surgeons perform breast carcinoma surgery on any particular
day of the menstrual cycle.
PMID- 9655297
TI - Modulation of biomarkers in minimal breast carcinoma: a model for human breast
carcinoma progression.
AB - BACKGROUND: The widespread use of diagnostic breast imaging has yielded an
increase in the detection of in situ, microinvasive, and small invasive
carcinomas and has provided opportunities to study the earliest stages of breast
carcinoma development. The authors of this report analyzed the pathobiologic
features of 577 minimal breast carcinomas (MBCs), including in situ carcinomas
and invasive carcinomas < or =1 cm, according to the definition given by Hartmann
in Cancer (1984;53:681-4). METHODS: Estrogen and progesterone receptors (ER and
PR), proliferation index (PI), and p53 and neu expression were studied by
immunohistochemical technique and measured by quantitative image analysis in 99
pure in situ carcinomas (ISCp); in 105 mixed invasive/in situ carcinomas, with a
separate analysis of in situ (ISCm) and invasive (ICm) components; and in 373
invasive carcinomas < or =1 cm (IC). Follow-up data were available for 164
invasive carcinomas. RESULTS: A progressive increase in the levels of hormone
steroid receptors, from the lowest in ISCm to the highest in IC, was observed
(ER, P< 0.001; PR, P=0.005). Levels of PI and p53 expression were higher in ISCm
than in the other categories (PI, P=0.007; p53, P=0.046). Overexpression of neu
was greater in ICm than in IC (P=0.013). Younger women (< or =40 years) with
invasive carcinoma had worse biologic profiles, with lower ER (P < 0.001) and
higher PI (P=0.021), neu (P=0.008), and p53 (P=0.040). It was demonstrated
clinically that PI and neu were the biologic markers with the highest predictive
prognostic values in univariate analysis (PI for recurrence, P < 0.015; neu for
recurrence and overall survival, P < 0.001 and P < 0.007, respectively) and in
multivariate analysis (neu for recurrence and overall survival, P < 0.007 and P <
0.017, respectively). CONCLUSIONS: Biologic phenotypes of MBC can be interpreted
as reflecting a dimension of neoplastic progression capacity that is independent
of tumor size. This study suggests that biologic markers can be integrated with
traditional pathologic indicators for accurate staging of patients.
PMID- 9655298
TI - Body mass predicts the survival of patients with new International Federation of
Gynecology and Obstetrics Stage IB1 and IB2 cervical carcinoma treated with
radical hysterectomy.
AB - BACKGROUND: The authors evaluated the impact of body mass on survival and
morbidity of patients with new International Federation of Gynecology and
Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical
hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2
cervical carcinoma treated with radical hysterectomy were studied in a
multivariate logistic regression analysis. The body mass index (BMI) and the
ponderal index (PI) were used as measures of body mass and were analyzed as
predictors of recurrence, survival, and complications in light of the new staging
system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low
BMI or a high PI were predictive of poor survival. Tumor greatest dimension,
lymph node involvement, BMI, and PI were all independent predictors of survival
(P=0.0006). The only independent predictor of complications was para-aortic lymph
node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low
body mass, as indicated by a low BMI or a high PI, were found to have poor
survival after undergoing radical hysterectomy. Additional predictors of poor
survival included lymph node metastases and increased tumor size. BMI and PI are
more important predictors of survival than the new FIGO Stages IB1 and IB2. Body
mass is not predictive of complications.
PMID- 9655299
TI - Bax protein expression correlates with radiation-induced apoptosis in radiation
therapy for cervical carcinoma.
AB - BACKGROUND: Bax protein serves as a positive regulator of apoptosis by forming
heterodimers with bcl-2 protein, thereby promoting cell survival. It is unclear
whether the regulation of apoptosis reported in many studies is applicable to the
apoptotic phenomenon observed in conventional fractionated radiation therapy for
cervical carcinoma. METHODS: The authors assessed the relation between apoptosis
and the expression of Bax and bcl-2 protein in fractionated radiation therapy for
cervical carcinoma by using in situ nick end labeling (ISEL) and
immunohistochemical methods. RESULTS: Specimens were excised from the cervical
tumors of 20 patients before and after administration of a total irradiation dose
of 9 gray (Gy). The apoptotic cell index (AI) in tumor cells was 0.22% before
irradiation and 1.20% after the administration of the 9 Gy, which represented a
significant increase (P=0.0004). The positive rate of Bax protein increased from
15% (in 3 of 20 patients) before irradiation to 60% (in 12 of 20 patients) after
the 9 Gy was administered, a statistically significant change (P=0.0126). In
addition, there was a significant correlation between Bax protein expression and
apoptosis positivity after the 9 Gy was administered (P=0.018). CONCLUSIONS:
These results suggest that Bax protein is associated with apoptosis induced by
fractionated radiation therapy.
PMID- 9655300
TI - Progesterone therapy for endometrial carcinoma reduces cell proliferation but
does not alter apoptosis.
AB - BACKGROUND: Although the anticancer effects of progesterone therapy for patients
with endometrial carcinoma are widely acknowledged, a detailed assessment of the
resultant morphologic alterations in tumor tissue kinetics has hitherto been
lacking. METHODS: Biopsy and hysterectomy specimens of 14 endometrial carcinomas
(endometrioid-type) before and during progesterone therapy were studied to
clarify changes in apoptosis and cell proliferation and their relation to
morphologic alterations. The extent of squamous differentiation within tumor
lesions was also examined. RESULTS: In the good-response group, tumor cells took
on characteristics of normal endometrial gland cells in the secretory phase. A
positive correlation between reduction in the mitotic index and the degree of
morphologic alterations during hormone therapy was observed, but the frequency of
apoptotic cells did not vary. In both the good-response and poor-response groups,
development or enlargement of squamous areas was observed, in comparison with the
initial biopsy specimens. CONCLUSIONS: These results suggest that prolonged
progesterone administration can suppress cell proliferation in endometrial
carcinomas through tumor cell differentiation without altering apoptosis,
resulting in a shift in tissue kinetics toward a relative predominance of cell
deletion. In addition, increases in the occurrence of squamous areas within
tumors do not always appear to be related to treatment efficacy.
PMID- 9655301
TI - A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive
penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c
rasHa activation in malignant progression.
AB - BACKGROUND: Human papillomaviruses (HPV) have been implicated in the etiology of
anogenital squamous epithelial tumors. Of the 65 HPV strains, subtypes HPV-16 and
HPV-18 frequently are associated with malignant conditions and are capable of
transforming keratinocytes in vitro. However, additional cellular changes are
necessary to confer tumorigenicity to HPV-infected cells. Secondary events
implicated in the progression to malignancy include loss of tumor suppressor
genes such as p53 and/or activation of cellular oncogenes such as c-rasHa.
METHODS: Polymerase chain reaction (PCR) was used to identify HPV-16 or HPV-18
genetic sequence in primary penile squamous cell carcinoma and two inguinal lymph
node metastases. p53 and c-rasHa loci were analyzed by sequencing of PCR
amplified genomic DNA. RESULTS: HPV-18 but not HPV-16 infection was found in the
primary carcinoma and in inguinal metastases occurring 5 and 7 years after the
initial lesion. Sequence analysis did not identify any p53 mutations in the
primary carcinoma or its metastases. However, although the primary lesion and the
5-year metastasis encoded wild-type c-rasHa, the 7-year metastasis had a missense
mutation within c-rasHa codon 61. CONCLUSIONS: To the authors' knowledge, this is
the first report of an activating c-rasHa mutation associated with squamous cell
carcinoma of the penis. The presence of activated c-rasHa in the second
metastasis but not in the first metastasis or the primary lesion suggests that
activation of c-rasHa may be a late event in the malignant progression of HPV-18
associated penile squamous cell carcinoma. Analysis of additional samples from
primary lesions and their resultant metastases is necessary to elucidate the
incidence and significance of c-rasHa activation in penile squamous cell
carcinoma.
PMID- 9655302
TI - Modeling postradiation prostate specific antigen level kinetics: predictors of
rising postnadir slope suggest cure in men who remain biochemically free of
prostate carcinoma.
AB - BACKGROUND: The goals of this study are twofold: 1) to describe the postradiation
kinetics of nonrecurring prostate carcinoma based on prostate specific antigen
(PSA) levels in men who remain biochemically free of disease; and 2) to determine
predictors of all three components of the resulting piecewise exponential model
based on pretreatment and treatment characteristics. METHODS: Between March 1988
and May 1994, 153 patients with T1-T3 nonmetastatic prostate carcinoma were
treated definitively with radiation therapy and at last follow-up had not failed
biochemically (PSA rising on 2 consecutive occasions to a level > 1.0 ng/mL or 3
consecutive elevations). All patients were required to have at least 6
posttreatment PSA determinations and a minimum follow-up of 36 months. The median
follow-up was 53 months (range, 36-94 months). A piecewise exponential model was
used to describe the mean PSA levels because 1) the kinetics of postradiation PSA
levels appear to follow first-order rate processes, and 2) there is evidence that
PSA levels may rise slightly several years after treatment. Nonlinear mixed
effects modeling was used in this situation because of the aforementioned
nonlinearity and because variability between patients and within patients (PSA
variation) must be taken into account. In addition, this methodology allows for
modeling parameters as a function of patient and treatment characteristics.
RESULTS: The random effects model based on the entire patient population
demonstrated that PSA levels do not continue to drop 3 years after treatment, and
that in fact the levels begin to rise slowly between 2-3 years after treatment.
Pretreatment PSA was the only independent predictor of baseline PSA at time zero
(end of radiation therapy). Gleason score was the only independent predictor of
the rate of PSA decline after treatment, in which tumors with Gleason scores 7-10
drop at a slower rate than do tumors with Gleason scores 2-6. Finally,
pretreatment prostate volume was the only independent predictor of the postnadir
rise in PSA level, in which larger volumes translate to a steeper slope.
CONCLUSIONS: The fact that pretreatment PSA level is the only independent
predictor of the baseline PSA at time zero is not surprising. The observation
that patients with tumors with higher Gleason scores have a slower rate of
decline is in agreement with previous reports that these tumors contribute less
PSA per unit volume than do tumors with moderate to well differentiation.
Finally, the fact that no tumor-related characteristic (only pretreatment
prostate volume) was predictive independently of the observed postnadir rise in
PSA level suggests that these patients were cured.
PMID- 9655303
TI - Correlation of color Doppler flow in the prostate with tissue microvascularity.
AB - BACKGROUND: The pathophysiology of increased color Doppler (CD) flow has not
previously been addressed in histologic evaluations of microvascular parameters.
In this study, the authors attempted to define the differences between benign and
malignant biopsy cores found in regions of the prostate with normal and high CD
flow. METHODS: Forty patients were retrospectively chosen for CD histologic
comparison, each of whom had a core from a sextant biopsy with the following
characteristics: malignant tissue with distinct increased CD flow (n=11),
malignant tissue with normal CD flow (n=10), benign tissue with distinctly
increased CD flow (n=9), or benign tissue with normal CD flow (n=10). All biopsy
cores were stained with factor VIII-related antigen to identify microvasculature
and to determine the number of microvessels per square millimeter (mm2) in an
average cross-sectional area of microvessels, the percentage of tissue occupied
by microvasculature, and the Gleason score. RESULTS: In biopsies of benign
tissue, high CD flow was associated with greater numbers (P < 0.025) of vessels
of similar size than in normal flow benign biopsies. Biopsies of malignant tissue
contained significantly greater numbers (P < 0.01) of much smaller vessels (P <
0.0005) than biopsies of benign tissue. In biopsies of malignant tissue, no
significant differences in microvasculature parameters were noted between high
and normal CD flow, yet biopsies with high CD flow had average Gleason score of
6.7 compared with only 5.9 for biopsies with normal CD flow (P < 0.025).
CONCLUSIONS: Increased CD flow in biopsies of benign tissue was correlated with a
greater number of vessels/mm2, yet all biopsies of malignant tissue had more
vessels/mm2 than those of benign tissue. Increased CD flow in biopsies of
malignant tissue cannot be explained by standard microvasculature analysis but
significantly guides biopsies to regions with a greater Gleason score.
PMID- 9655304
TI - Radical cystectomy for elderly patients with bladder carcinoma: an updated
experience with 404 patients.
AB - BACKGROUND: The authors evaluated the experiences at their institution with
radical cystectomy and urinary diversion performed on elderly bladder carcinoma
patients to determine whether age had an impact on the clinical or functional
results for this group of patients. METHODS: Between August 1971 and December
1996, 404 patients age 70 years or older (median age, 74 years) underwent radical
cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were
ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included
the following: perioperative mortality; early (within 90 days after surgery) and
late (more than 90 days after surgery) postoperative complications, related and
unrelated to the urinary diversion; length of hospital stay; pathologic staging;
and clinical outcome. These data were then compared with those for 762 patients
younger than 70 years (median age, 61 years) who underwent the same procedure
during the same time period. RESULTS: The overall mortality rate for patients age
70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80
years or older), compared with 2% for patients younger than 70 years. The early
complication rate for patients age 70 years or older was 32%, compared with 25%
for patients younger than 70 years. Patients age 80 years or older had a similar
early complication rate of 29%. Late postoperative complications occurred in
12.4% of patients age 70 years or older, compared with 22.8% of patients younger
than 70 years. There was no significant difference between the two groups with
regard to pathologic stage or length of hospital stay. The 3-year and 5-year
overall survival rates for patients age 70 years or older were 60% and 53%,
respectively, compared with 68% and 63%, respectively, for patients younger than
70 years (P=0.001). There was no statistical difference between the groups when
rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate
for patients age 70 years or older was 35%, compared with a 5-year recurrence
rate of 31% for patients younger than 70 years. CONCLUSIONS: These data suggest
that an aggressive, curative, radical surgical approach and urinary diversion may
be a viable treatment strategy for properly selected elderly patients who are in
generally good health and require definitive therapy for invasive bladder
carcinoma.
PMID- 9655305
TI - Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using
intralesional bleomycin.
AB - BACKGROUND: Electrochemotherapy (ECT) is performed by locally administering a
chemotherapeutic agent in combination with electric pulses. Previous clinical
studies have demonstrated the effectiveness of ECT. In these initial trials, the
drug was administered intravenously, followed by administration of electric
pulses directly to the tumor. This study was initiated to determine whether an
intralesional injection of the drug in combination with electric pulses could
provide an improved result. A group of 34 patients was studied. METHODS: The dose
of intralesional bleomycin was based on tumor volume. This was followed 10
minutes later by 6 or 8 99-microsec pulses of electricity at an amplitude of 1.3
kV/cm. Both the bleomycin and the electric pulses were administered after 1%
lidocaine with epinephrine solution was injected around the treatment site.
RESULTS: All patients responded to the treatment. Responses were observed in 142
(99%) of 143 metastatic nodules or primary tumors within 12 weeks, with complete
responses observed in 130 (91%) of the nodules. No complete responses were
observed in nodules treated with bleomycin only or electric pulses only. Random
biopsies confirmed the clinical findings. All patients tolerated the procedure
well, and no significant side effects were noted. Muscle contraction was evident
during administration of each electric pulse but promptly subsided after the
pulse. CONCLUSIONS: ECT was shown to be an effective local treatment for
cutaneous malignancies. The results suggest that ECT may have a tissue-sparing
effect and result in minimal scarring. ECT may be a suitable alternative therapy
for the treatment of basal cell carcinoma, local or regional recurrent melanoma,
and other skin cancers.
PMID- 9655306
TI - Cell turnover parameters in small and large cell varieties of primary intestinal
non-Hodgkin's lymphoma.
AB - BACKGROUND: In contrast to primary gastric lymphoma, primary intestinal lymphoma
is an uncommon condition with a poorer outcome, perhaps due to differences in its
pathogenesis. In this study, the authors analyzed the roles of proliferation and
apoptosis in the pathogenesis of intestinal lymphoma. METHODS: Fifty-one cases of
intestinal non-Hodgkin's lymphoma (NHL) (10 small B-cell mucosa-associated
lymphoid tissue [MALT] NHLs, 12 large B-cell MALT NHLs, 18 large B-cell NHLs, 2
small T-cell NHLs, 7 large T-cell NHLs, and 2 mantle cell NHLs) were studied for
the immunohistochemical expression of MIB-1 and the TUNEL assay as well as the
expression of bcl-2 and p53, both of which are regulatory gene products involved
in apoptosis. RESULTS: The median proliferation index (PI) was 37.3%, and the
median apoptotic index (AI) was 1.10%. The respective values of PI and AI were
5.8% and 0.06% in small B-cell MALT lymphoma, 52.8% and 0.24% in large B-cell
MALT lymphoma, 58.85% and 1.36% in large B-cell lymphoma, 30.9% and 1.93% in
mantle cell lymphoma, 18.13% and 1.25% in small T-cell lymphoma, and 43.4% and
1.93% in large T-cell lymphoma. In an analysis of B-cell NHL only (with mantle
cell NHL excluded), proliferative and apoptotic indices were positively
correlated (correlation coefficient=0.563, P < 0.001). Furthermore, high bcl-2
expression was inversely correlated with both PI and AI. Expression of p53 was
observed in 8 cases (1 small cell lymphoma and 7 large cell lymphomas).
CONCLUSIONS: Small cell lymphomas had low AI and PI values, whereas large cell
lymphomas had high AI and PI values. Apoptosis and proliferation were positively
correlated, and higher expression of bcl-2 was associated with lower rates of
apoptosis.
PMID- 9655307
TI - Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and
long term control.
AB - BACKGROUND: The diencephalic syndrome (DS), which is manifested by progressive
emaciation and failure to thrive in an apparently alert, cheerful infant, usually
is due to a low grade hypothalamic glioma. Treatment with aggressive surgery
and/or radiotherapy is variably successful in controlling disease and may result
in severe neurologic sequelae. Chemotherapy recently has been shown to be
effective in patients with low grade gliomas of childhood, but it is used
infrequently in those with DS. METHODS: The authors evaluated the efficacy of a
regimen of carboplatin and vincristine on improving weight, causing tumor
shrinkage, and delaying the need for alternative therapies in seven children
(ages 9-20 months; median age, 11 months) with DS. Five patients weighed less
than the 5th percentile for their age at the start of the study, one weighed
within the 10th percentile, and one weighed within the 25th percentile. RESULTS:
At follow-up (range, 6-54 months; median, 28 months), the patients' weights had
increased by 66-95% (median, 80%). On magnetic resonance imaging, four patients
had a >50% reduction in tumor mass, one had a 25-50% reduction, and two had
stable disease. In those patients with radiographic response to treatment, weight
gain was accomplished with oral feedings in four of five patients, whereas those
with stable disease required nasogastric, nasojejunal, or gastrostomy tube
supplementation to maintain weight. Disease progression occurred at a median of
24 months after initiation of chemotherapy, and two patients remained free of
progressive disease at last follow-up. Five patients were alive a median of 59
months from diagnosis. The need for radiation or other therapies was delayed in
six of seven children. Therapy was tolerated without significant toxicities.
CONCLUSION: The authors conclude that treatment of DS with a carboplatin and
vincristine regimen results in demonstrable weight gain, may result in tumor
shrinkage, and in some cases, significantly delays the need for alternative
therapies.
PMID- 9655308
TI - Quality of life and survival: the role of multidimensional symptom assessment.
AB - BACKGROUND: Recent data from clinical trials suggest that quality-of-life (QOL)
measurements may independently predict survival. The relation between survival
and QOL measurements was tested among 122 inpatients and 96 outpatients with
malignancies at one of four sites (colon, breast, ovary, or prostate) who
participated in a cross-sectional validation study of the Memorial Symptom
Assessment Scale (MSAS), a measure of the frequency of, severity of, and distress
caused by physical symptoms. METHODS: The relation between MSAS summary scores
and survival was evaluated in a multivariate analysis that adjusted concurrently
for other important covariates, such as age, site and extent of disease,
inpatient status, Karnofsky performance status (KPS), and other QOL measurements.
RESULTS: In the multivariate analysis, extent of disease (P < 0.0001), inpatient
status (P=0.014), higher MSAS physical symptom subscale score (P=0.004), and
lower KPS score (P=0.009) independently predicted decreased survival. Other QOL
measurements did not contribute significantly to the model. CONCLUSIONS: The MSAS
physical symptom subscale score significantly predicts survival and adds to the
prognostic information provided by KPS and extent of disease. Patients may be
under-assessed regarding both the number and the severity of symptoms.
Measurements of physical symptoms and related distress offer additional
prognostic information concerning the survival of patients with cancer and may
account for the predictive value of QOL scores.
PMID- 9655309
TI - Undiagnosed malignancy in patients with deep vein thrombosis: incidence, risk
indicators, and diagnosis.
AB - BACKGROUND: The reported incidence of a subsequent diagnosis of malignancy in
patients presenting with deep vein thrombosis (DVT) varies from 2-25%. Risk
indicators and diagnostic procedures to be performed in these patients are
controversial. METHODS: Four hundred consecutive patients with confirmed DVT
included in a randomized clinical trial were followed prospectively for 6 months.
The incidence of a subsequent diagnosis of malignancy was calculated and compared
between patients with unexplained DVT and patients with secondary DVT. Potential
risk indicators for subsequent malignant disease were evaluated. RESULTS: Of the
400 patients, 70 already had been diagnosed with malignancy; another four
patients were lost to follow-up. Of the remaining 326 patients, 10 new
malignancies were diagnosed among 137 patients with unexplained DVT (7.3%) and 3
new malignancies were diagnosed in 189 patients with secondary DVT (1.6%). The
relative risk was 4.6 (95% confidence interval, 1.3-16; P=0.009). Age, gender, or
location of the DVT had no significant effect on the incidence of diagnosis when
adjusted for unexplained DVT. Ten of these 13 patients (77%) had abnormal
clinical findings suggestive of malignancy at the time of presentation with DVT.
CONCLUSIONS: Unexplained DVT is a significant risk indicator of underlying
malignancy. The majority of patients with undiagnosed malignancy have some
clinical abnormality suggestive of underlying malignancy at the time of
presentation with unexplained DVT. A simple clinical evaluation comprised of
medical history, physical examination, routine laboratory tests, and chest X-ray
can detect such patients. Extensive screening of all patients presenting with
unexplained DVT does not appear to be justified.
PMID- 9655310
TI - The Gothenburg breast screening trial: first results on mortality, incidence, and
mode of detection for women ages 39-49 years at randomization.
PMID- 9655311
TI - Acute infectious purpura fulminans: pathogenesis and medical management.
AB - Purpura fulminans (PF) is a potentially disabling and life-threatening disorder
characterized by acute onset of progressive cutaneous hemorrhage and necrosis,
and disseminated intravascular necrosis. Acute infectious PF occurs most commonly
in the setting of meningococcemia due to elaboration of endotoxin. Presence of
purpura, particularly when generalized, is an important predictor of a poor
outcome following meningococcal infection. Histopathologic hallmarks of acute
infectious PF are dermal vascular thrombosis and secondary hemorrhagic necrosis,
findings which are identical to those of the Shwartzman reaction. Acute
infectious PF and the Shwartzman reaction have a common pathogenesis, involving a
disturbance in the balance of anticoagulant and procoagulant activities of
endothelial cells. This disturbance, which is triggered by endotoxin, appears to
be mediated by cytokines, particularly interleukin-12, interferon-gamma, tumor
necrosis factor-alpha, and interleukin-1, leading to the consumption of proteins
C and S and antithrombin III. State-of-the-art therapeutic interventions based on
recent advances in our understanding of the pathogenesis of acute infectious PF
are discussed.
PMID- 9655312
TI - Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis,
and immunopathology in 11 children.
AB - The immunobullous diseases bullous pemphigoid (BP) and epidermolysis bullosa
acquisita (EBA) are very rare in childhood. Although case studies have been
detailed, there are no reports of a large series of patients documenting the
effectiveness of treatment and long-term prognosis. We report the clinical
presentation, immunopathologic features, disease course, and long-term prognosis
of BP and EBA in a series of 11 children. The initial diagnoses based on clinical
features were BP (5), EBA (3), and chronic bullous disease of childhood (CBDC)
(3). These were subsequently revised from BP to EBA (2), CBDC to BP (2), and CBDC
to BP or EBA (1) following the results of direct and indirect immunofluorescence
and immunoblotting. Analysis of IgG subclasses in eight cases showed that the
predominant subclasses were IgG1 (8) and IgG4 (6). The clinical features appeared
to be highly variable, and in patients presenting with inflammatory blistering,
laboratory studies were required in order to differentiate between BP and EBA.
All patients improved on treatment with corticosteroids and/or sulfones, although
treatment regimens showed wide variation. Their diseases tended to remit within 2
years, and their long-term prognosis was good.
PMID- 9655313
TI - Median raphe cysts of the penis: a report of five cases.
AB - Cysts of the median raphe are embryologic developmental anomalies of the male
genitalia. Although generally present since birth, these lesions tend to manifest
in adult life. Histologically the cysts are characterized by a pseudostratified
epithelium in the middle dermis. The early age at consultation is a common
characteristic in four of the five patients reported herein and is probably due
to the growing concern among the general population about skin problems.
PMID- 9655314
TI - S. aureus isolation from the lesions, the hands, and the anterior nares of
patients with atopic dermatitis.
AB - Staphylococcus aureus colonization is common in atopic dermatitis (AD) and can
exacerbate the disease. Additionally, some evidence shows that patients with AD
may act as reservoirs for S. aureus transmission to others. This study compared
S. aureus colonization in AD patients and their caregivers with control patients
and their caregivers. Quantitative cultures were obtained from the lesions,
clinically normal skin, hands, and anterior nares of 100 patients with AD, 100
controls with other cutaneous disorders, and 200 caregivers. AD patients had a
significantly greater carriage of S. aureus from lesional and clinically normal
skin as well as the hand. Significant increases in carriage of S. aureus were
found in the anterior nares and hands of caregivers of AD patients compared with
control caregivers. Topical corticosteroid use did not affect recovery of S.
aureus. There was a significant correlation between recovery of S. aureus from
lesional skin and recovery from the anterior nares (p = .002) and hands (p <
.0001). These findings suggest that the anterior nares and the hands may be
important reservoirs and vectors for transmission of S. aureus to lesional skin
and to close contacts of these patients.
PMID- 9655315
TI - Resolution of xanthomas in Alagille syndrome after liver transplantation.
AB - Alagille syndrome (arteriohepatic dysplasia) is a genetic disorder with autosomal
dominant transmission which has been localized to chromosome 20p. Cutaneous
manifestations include jaundice, pruritus, and widespread xanthomata. We report a
child with severe Alagille syndrome in whom orthotopic liver transplantation
caused rapid resolution of disfiguring xanthomas.
PMID- 9655316
TI - Juvenile xanthogranuloma with hematologic changes in dizygotic twins: report of
two newborn infants.
AB - We describe the first reported instances of juvenile xanthogranuloma (JXG) in
dizygotic twins. They had characteristic skin lesions and subcutaneous nodules as
well as hepatomegaly, anemia, and thrombocytopenia. These extracutaneous symptoms
improved in 5 months, coincident with the resolution of the skin lesions.
Although most patients with JXG have only cutaneous symptoms, some show such
dramatic extracutaneous manifestations that the possibility of malignant disease
is occasionally the principle concern. It is therefore necessary to make a
precise diagnosis based on specific immunohistochemical and ultrastructural
findings, and to evaluate for other organ involvement, including hematologic
abnormalities.
PMID- 9655317
TI - Scleroatrophic syndrome of Huriez in an infant.
AB - We present a 3-year-old boy with scleroatrophic syndrome of Huriez, a rare
autosomal dominant condition with only seven affected families worldwide.
Although assumed to occur from birth, an evolving case has not previously been
documented. Infants do not possess the focal areas of keratoderma on the palms or
soles; these develop in adult life. Of particular interest is the high incidence
of squamous cell carcinomas that arise from the scleroatrophic skin.
PMID- 9655318
TI - Congenital lipoblastomatosis of the lower extremity in a neonate.
AB - Lipoblastomatosis is a benign tumor of embryonic fat that is more common in male
infants. It occurs more frequently in the soft tissues of the extremities. The
diagnosis is made by biopsy, which shows globules of lipocytes and lipoblasts
mixed with spindled and myxoid cells. MRI demonstrates fat infiltrating fascia
and muscle. The infant described had clinical, histologic, and radiologic
findings consistent with this diagnosis. Because of concern that total excision
would compromise function, a debulking procedure is planned.
PMID- 9655319
TI - Congenital erosive and vesicular dermatosis healing with reticulated supple
scarring: report of three new cases and review of the literature.
AB - Congenital erosive and vesicular dermatosis healing with reticulated, supple
scarring is a rare disease with seven reported cases in the literature. This
congenital cutaneous defect of unknown etiology presents with patchy or
generalized erosions and vesicles at birth that heal with striking reticulated
scarring. We report three new cases of this rare disease and review the
literature.
PMID- 9655320
TI - Keratitis, ichthyosis, and deafness (KID) syndrome in half sibs.
AB - The keratitis, ichthyosis, and deafness (KID) syndrome is a rare congenital
disorder of the ectoderm characterized by diffuse hyperkeratotic erythroderma,
keratitis with neovascularization of the cornea, and severe neurosensory hearing
loss. A familial occurrence of this syndrome has been mentioned in four reports
including three of vertical transmission and one of two affected sisters born
from consanguineous, unaffected parents. We report for the first time a familial
case of KID syndrome in two half siblings born to the same unaffected mother.
This new observation allows us to propose various hypotheses about its mode of
inheritance.
PMID- 9655321
TI - Solitary giant molluscum contagiosum of the sole.
AB - Molluscum contagiosum of the sole is extremely rare and only three cases have
been reported in the literature. We report a solitary giant molluscum contagiosum
on the left sole of a 5-year-old boy, which should be clinically differentiated
from plantar wart, eccrine poroma, epidermal cyst, foreign body granuloma,
cryptococcal infection, and pyogenic granuloma.
PMID- 9655322
TI - Itraconazole pulse therapy for tinea capitis: a novel treatment schedule.
AB - Itraconazole 5 mg/kg/day given as pulse therapy, each of 1 week duration, for 1
to 3 pulses appears to be an effective and safe method of treating tinea capitis.
The number of pulses of therapy may depend upon several factors, including the
severity of disease and area of involvement. Controlled studies are needed to
determine the number of pulses of itraconazole required to treat tinea capitis.
PMID- 9655323
TI - Tinea capitis: fluconazole in Trichophyton tonsurans infection.
AB - Tinea capitis is the most common dermatophyte infection in children. Trichophyton
tonsurans is the most common etiologic agent in the United States, and for more
than four decades the standard therapy has been griseofulvin. The availability of
newer, and often more effective, antifungal drugs creates the opportunity for
choice and the ability to optimally tailor treatment for a particular patient.
Fluconazole is an azole antifungal drug available in a pleasant, well-tolerated,
liquid formulation ideal for the pediatric population. It has a good safety
profile and is approved in the United States for use in children, although not
for tinea capitis. We present five patients with tinea capitis successfully
treated with fluconazole.
PMID- 9655324
TI - Pigmented palmar patch in a child.
PMID- 9655325
TI - What syndrome is this? Waardenburg syndrome.
PMID- 9655326
TI - Peripheral nerve blocks for warts: taking the cry out of cryotherapy and laser.
PMID- 9655327
TI - Acropigmentation of Dohi in a 12-year-old boy.
PMID- 9655328
TI - Colocalization of vitiligo and psoriasis in a 9-year-old boy.
PMID- 9655329
TI - The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A
complexed with the enzyme reaction product throws light on its enzymatic
function.
AB - Dihydroorotate dehydrogenases (DHODs) catalyze the oxidation of (S)
dihydroorotate to orotate, the fourth step and only redox reaction in the de novo
biosynthesis of pyrimidine nucleotides. A description is given of the crystal
structure of Lactococcus lactis dihydroorotate dehydrogenase A (DHODA) complexed
with the product of the enzyme reaction orotate. The structure of the complex to
2.0 A resolution has been compared with the structure of the native enzyme. The
active site of DHODA is known to contain a water filled cavity buried beneath a
highly conserved and flexible loop. In the complex the orotate displaces the
water molecules from the active site and stacks above the DHODA flavin
isoalloxazine ring, causing only small movements of the surrounding protein
residues. The orotate is completely buried beneath the protein surface, and the
orotate binding causes a significant reduction in the mobility of the active site
loop. The orotate is bound by four conserved asparagine side chains (Asn 67, Asn
127, Asn 132, and Asn 193), the side chains of Lys 43 and Ser 194, and the main
chain NH groups of Met 69, Gly 70, and Leu 71. Of these the Lys 43 side chain
makes hydrogen bonds to both the flavin isoalloxazine ring and the carboxylate
group of the orotate. Potential interactions with bound dihydroorotate are
considered using the orotate complex as a basis for molecular modeling. The role
of Cys 130 as the active site base is discussed, and the sequence conservation of
the active site residues across the different families of DHODs is reviewed,
along with implications for differences in substrate binding and in the catalytic
mechanisms between these families.
PMID- 9655330
TI - Circular permutation of betaB2-crystallin changes the hierarchy of domain
assembly.
AB - The betagamma-crystallins form a superfamily of eye lens proteins comprised of
multiple Greek motifs that are symmetrically organized into domains and higher
assemblies. In the betaB2-crystallin dimer each polypeptide folds into two
similar domains that are related to monomeric gamma-crystallin by domain
swapping. The crystal structure of the circularly permuted two-domain betaB2
polypeptide shows that permutation converts intermolecular domain pairing into
intramolecular pairing. However, the dimeric permuted protein is, in fact, half a
native tetramer. This result shows how the sequential order of domains in multi
domain proteins can affect quaternary domain assembly.
PMID- 9655331
TI - Crystal structure of cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase from a PCB
degrader at 2.0 A resolution.
AB - cis-Biphenyl-2,3-dihydrodiol-2,3-dehydrogenase (BphB) is involved in the aerobic
biodegradation of polychlorinated biphenyls (PCBs). The crystal structure of the
NAD+-enzyme complex was determined by molecular replacement and refined to an R
value of 17.9% at 2.0 A. As a member of the short-chain alcohol
dehydrogenase/reductase (SDR) family, the overall protein fold and positioning of
the catalytic triad in BphB are very similar to those observed in other SDR
enzymes, although small differences occur in the cofactor binding site. Modeling
studies indicate that the substrate is bound in a deep hydrophobic cleft close to
the nicotinamide moiety of the NAD+ cofactor. These studies further suggest that
Asn143 is a key determinant of substrate specificity. A two-step reaction
mechanism is proposed for cis-dihydrodiol dehydrogenases.
PMID- 9655332
TI - Crystal structure of human cathepsin S.
AB - We have determined the 2.5 A structure (Rcryst = 20.5%, Rfree = 28.5%) of a
complex between human cathepsin S and the potent, irreversible inhibitor 4
morpholinecarbonyl-Phe-hPhe-vinyl sulfone-phenyl. Noncrystallographic symmetry
averaging and other density modification techniques were used to improve electron
density maps which were nonoptimal due to systematically incomplete data. Methods
that reduce the number of parameters were implemented for refinement. The refined
structure shows cathepsin S to be similar to related cysteine proteases such as
papain and cathepsins K and L. As expected, the covalently-bound inhibitor is
attached to the enzyme at Cys 25, and enzyme binding subsites S3-S1' are occupied
by the respective inhibitor substituents. A somewhat larger S2 pocket than what
is found in similar enzymes is consistent with the broader specificity of
cathepsin S at this site, while Lys 61 in the S3 site may offer opportunities for
selective inhibition of this enzyme. The presence of Arg 137 in the S1' pocket,
and proximal to Cys 25 may have implications not only for substrate specificity C
terminal to the scissile bond, but also for catalysis.
PMID- 9655333
TI - Structure of malonic acid-based inhibitors bound to human neutrophil collagenase.
A new binding mode explains apparently anomalous data.
AB - Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, which have
been implicated in various disease processes. Various classes of MMP inhibitors,
including hydroxamic acids, phosphinic acids, and thiols, have been previously
described. Most of these mimic peptides, and most likely bind analogous to the
corresponding peptide substrates. Among the hydroxamic acids, malonic acid
derivatives have been used as MMP inhibitors, although optimization of their
inhibition potency was not successful. Here we report the design of malonic acid
based inhibitors using the X-ray structure of a collagenase/inhibitor complex,
which revealed a nonsubstrate-like binding mode. The proposed beta-type turn-like
conformation for the improved inhibitors was confirmed by X-ray crystallography.
The observation of nonsubstrate-like binding confirms the original strategy for
structure-based modeling of improved malonic acid inhibitors, and explains
kinetic data that are inconsistent with substrate-like binding. Detailed
interactions for the improved inhibitors seen in the crystal structure also
suggest possibilities for further modifications in cycles of structure based drug
design. Indeed, we have designed nonpeptidic inhibitors with approximately 500
fold improved inhibition based on these structures.
PMID- 9655334
TI - Crystal structure of the cyclophilin-like domain from the parasitic nematode
Brugia malayi.
AB - Cyclophilins are a family of proteins that exhibit peptidyl-prolyl cis-trans
isomerase activity and bind the immunosuppressive agent cyclosporin A (CsA).
Brugia malayi is a filarial nematode parasite of humans, for which a cyclophilin
like domain was identified at the N-terminal of a protein containing 843 amino
acid residues. There are two differences in sequence in the highly conserved CsA
binding site: A histidine and a lysine replace a tryptophan and an alanine,
respectively. The crystal structure of this domain has been determined by the
molecular replacement method and refined to an R-factor of 16.9% at 2.15 A
resolution. The overall structure is similar to other cyclophilins; however,
major differences occur in two loops. Comparison of the CsA binding site of this
domain with members of the cyclophilin family shows significant structural
differences, which can account for the reduced sensitivity of the Brugia malayi
protein to inhibition by CsA.
PMID- 9655335
TI - Structural investigation of the A domains of human blood coagulation factor V by
molecular modeling.
AB - Factor V (FV) is a large (2,196 amino acids) nonenzymatic cofactor in the
coagulation cascade with a domain organization (A1-A2-B-A3-C1-C2) similar to the
one of factor VIII (FVIII). FV is activated to factor Va (FVa) by thrombin, which
cleaves away the B domain leaving a heterodimeric structure composed of a heavy
chain (A1-A2) and a light chain (A3-C1-C2). Activated protein C (APC), together
with its cofactor protein S (PS), inhibits the coagulation cascade via limited
proteolysis of FVa and FVIIIa (APC cleaves FVa at residues R306, R506, and R679).
The A domains of FV and FVIII share important sequence identity with the plasma
copper-binding protein ceruloplasmin (CP). The X-ray structure of CP and
theoretical models for FVIII have been recently reported. This information
allowed us to build a theoretical model (994 residues) for the A domains of human
FV/FVa (residues 1-656 and 1546-1883). Structural analysis of the FV model
indicates that: (a) the three A domains are arranged in a triangular fashion as
in the case of CP and the organization of these domains should remain essentially
the same before and after activation; (b) a Type II copper ion is located at the
A1-A3 interface; (c) residues R306 and R506 (cleavage sites for APC) are both
solvent exposed; (d) residues 1667-1765 within the A3 domain, expected to
interact with the membrane, are essentially buried; (e) APC does not bind to FVa
residues 1865-1874. Several other features of factor V/Va, like the R506Q and
A221V mutations; factor Xa (FXa) and human neutrophil elastase (HNE) cleavages;
protein S, prothrombin and FXa binding, are also investigated.
PMID- 9655336
TI - Crystal structure of apo-glycine N-methyltransferase (GNMT).
AB - The crystal structure of the recombinant apo-form of glycine N-methyltransferase
(GNMT) has been determined at 2.5 A resolution. GNMT is a tetrameric enzyme
(monomer Mr = 32,423Da, 292 amino acids) that catalyzes the transfer of a methyl
group from S-adenosylmethionine (AdoMet) to glycine with the formation of S
adenosylhomocysteine (AdoHcy) and sarcosine (N-methylglycine). GNMT is a
regulatory enzyme, which is inhibited by 5-methyltetrahydrofolate pentaglutamate
and believed to control the ratio of AdoMet to AdoHcy in tissues. The crystals
belong to the orthorhombic space group P2(1)2(1)2 (a = 85.39, b = 174.21, c =
44.71 A) and contain one dimer per asymmetric unit. The AdoMet-GNMT structure
served as the starting model. The structure was refined to an R-factor of 21.9%.
Each monomer is a three-domain structure with a large cavity enclosed by the
three domains. The tetramer resembles a square with a central channel about which
N-terminal domains are intertwined. Only localized changes of the residues
involved in the binding pocket are observed for the apo-GNMT structure when
compared to that determined in the presence of substrate and substrate analog.
PMID- 9655337
TI - The three-dimensional structure of a helix-less variant of intestinal fatty acid
binding protein.
AB - Intestinal fatty acid-binding protein (I-FABP) is a cytosolic 15.1-kDa protein
that appears to function in the intracellular transport and metabolic trafficking
of fatty acids. It binds a single molecule of long-chain fatty acid in an
enclosed cavity surrounded by two five-stranded antiparallel beta-sheets and a
helix-turn-helix domain. To investigate the role of the helical domain, we
engineered a variant of I-FABP by deleting 17 contiguous residues and inserting a
Ser-Gly linker (Kim K et al., 1996, Biochemistry 35:7553-7558). This variant,
termed delta17-SG, was remarkably stable, exhibited a high beta-sheet content and
was able to bind fatty acids with some features characteristic of the wild-type
protein. In the present study, we determined the structure of the delta17
SG/palmitate complex at atomic resolution using triple-resonance 3D NMR methods.
Sequence-specific 1H, 13C, and 15N resonance assignments were established at pH
7.2 and 25 degrees C and used to define the consensus 1H/13C chemical shift
derived secondary structure. Subsequently, an iterative protocol was used to
identify 2,544 NOE-derived interproton distance restraints and to calculate its
tertiary structure using a unique distance geometry/simulated annealing
algorithm. In spite of the sizable deletion, the delta17-SG structure exhibits a
backbone conformation that is nearly superimposable with the beta-sheet domain of
the wild-type protein. The selective deletion of the alpha-helical domain creates
a very large opening that connects the interior ligand-binding cavity with
exterior solvent. Unlike wild-type I-FABP, fatty acid dissociation from delta17
SG is structurally and kinetically unimpeded, and a protein conformational
transition is not required. The delta17-SG variant of I-FABP is the only wild
type or engineered member of the intracellular lipid-binding protein family whose
structure lacks alpha-helices. Thus, delta17-SG I-FABP constitutes a unique model
system for investigating the role of the helical domain in ligand-protein
recognition, protein stability and folding, lipid transfer mechanisms, and
cellular function.
PMID- 9655338
TI - Comparative analysis of the noncollagenous NC1 domain of type IV collagen:
identification of structural features important for assembly, function, and
pathogenesis.
AB - Type IV collagen alpha1-alpha6 chains have important roles in the assembly of
basement membranes and are implicated in the pathogenesis of Goodpasture
syndrome, an autoimmune disorder, and Alport syndrome, a hereditary renal
disease. We report comparative sequence analyses and structural predictions of
the noncollagenous C-terminal globular NC1 domain (28 sequences). The inferred
tree verified that type IV collagen sequences fall into two groups, alpha1-like
and alpha2-like, and suggested that vertebrate alpha3/alpha4 sequences evolved
before alpha1/alpha2 and alpha5/alpha6. About one fifth of NC1 residues were
identified to confer either the alpha1 or alpha2 group-specificity. These
residues accumulate opposite charge in subdomain B of alpha1 (positive) and
alpha2 (negative) sequences and may play a role in the stoichiometric chain
selection upon type IV collagen assembly. Neural network secondary structure
prediction on multiple aligned sequences revealed a subdomain core structure
consisting of six hydrophobic beta-strands and one short alpha-helix with a
significant hydrophobic moment. The existence of opposite charges in the alpha
helices may carry implications for intersubdomain interactions. The results
provide a rationale for defining the epitope that binds Goodpasture
autoantibodies and a framework for understanding how certain NC1 mutations may
lead to Alport syndrome. A search algorithm, based entirely on amino acid
properties, yielded a possible similarity of NC1 to tissue inhibitor of
metalloproteinases (TIMP) and prompted an investigation of a possible functional
relationship. The results indicate that NC1 preparations decrease the activity of
matrix metalloproteinases 2 and 3 (MMP-2, MMP-3) toward a peptide substrate,
though not to [14C]-gelatin. We suggest that an ancestral NC1 may have been
incorporated into type IV collagen as an evolutionarily mobile domain carrying
proteinase inhibitor function.
PMID- 9655339
TI - Thermodynamic characterization of an intermediate state of human growth hormone.
AB - The thermal denaturation of recombinant human growth hormone (rhGH) was studied
by differential scanning calorimetry and circular dichroism spectroscopy (CD).
The thermal unfolding is reversible only below pH 3.5, and under these conditions
a single two-state transition was observed between 0 and 100 degrees C. The
magnitudes of the deltaH and deltaCp of this transition indicate that it
corresponds to a partial unfolding of rhGH. This is also supported by CD data,
which show that significant secondary structure remains after the unfolding.
Above pH 3.5 the thermal denaturation is irreversible due to the aggregation of
rhGH upon unfolding. This aggregation is prevented in aqueous solutions of
alcohols such as n-propanol, 2-propanol, or 1,2-propanediol (propylene glycol),
which suggests that the self-association of rhGH is caused by hydrophobic
interactions. In addition, it was found that the native state of rhGH is stable
in relatively high concentrations of propylene glycol (up to 45% v/v at pH 7-8 or
30% at pH 3) and that under these conditions the thermal unfolding is cooperative
and corresponds to a transition from the native state to a partially folded
state, as observed at acidic pH in the absence of alcohols. In higher
concentrations of propylene glycol, the tertiary structure of rhGH is disrupted
and the cooperativity of the unfolding decreases. Moreover, the CD and DSC data
indicate that a partially folded intermediate with essentially native secondary
structure and disordered tertiary structure becomes significantly populated in 70
80% propylene glycol.
PMID- 9655340
TI - Conformational change in the activation of lipase: an analysis in terms of low
frequency normal modes.
AB - The interfacial activation of Rhizomucor miehei lipase (RmL) involves the motion
of an alpha-helical region (residues 82-96) which acts as a "lid" over the active
site of the enzyme, undergoing a displacement from a "closed" to an "open"
conformation upon binding of substrate. Normal mode analyses performed in both
low and high dielectric media reveal that low-frequency vibrational modes
contribute significantly to the conformational transition between the closed and
open conformations. In these modes, the lid displacement is coupled to local
motions of active site loops as well as global breathing motions. Atomic
fluctuations of the first hinge of the lid (residues 83-84) are substantially
larger in the low dielectric medium than in the high dielectric medium. Our
results also suggest that electrostatic interactions of Arg86 play an important
role in terms of both the intrinsic stability of the lid and its displacement,
through enhancement of hinge mobility in a high dielectric medium. Additional
calculations demonstrate that the observed patterns of atomic fluctuations are an
intrinsic feature of the protein structure and not dependent on the nature of
specific energy minima.
PMID- 9655341
TI - Deciphering the structural code for proteins: helical propensities in domain
classes and statistical multiresidue information in alpha-helices.
AB - We made several statistical analyses in a large sample of nearly 4,000 helices
(from 546 redundancy-controlled PDB protein subunits), which give new insights
into the helical properties of globular proteins. In a first experiment, the
amino acid composition of the whole sample was compared with the composition of
two helical sample subgroups (the "mainly-alpha" and the "(alpha/beta)8 barrel"
domain classes); we reached the conclusion that composition-based helical
propensities for secondary structure prediction do not depend on the structural
class. Running a five-residue window through the whole sample, the positional
composition revealed that positive and negative residues are located throughout
the helices and tend to neutralize the macrodipole effect. On this basis, we
analyzed charged triplets using a running five-residue window. The conclusion was
that only mixed charged residues [positive (+) and negative (-)] located at
positions 1-2-5 and 1-4-5 are clearly favored. In these locations the most
abundant are (- -..+) and (-..+ +), and this shows the existence of side chain
microdipoles, which neutralize the large macrodipole of the helix. We made a
systematic statistical analysis of charged, dipolar, and hydrophobic + aromatic
residues, which enabled us to work out rules that should be useful for modeling
and design purposes. Finally, we analyzed the relative abundance of all the
different amphipathic double-arcs that are present in helices formed by
octapeptides (8) and nonapeptides (18). All of the double-arcs that make up
Schiffer and Edmundson's classical helical wheel are found in abundance in the
sample.
PMID- 9655342
TI - Crystal structure of Saccharomyces cerevisiae cytosolic aspartate
aminotransferase.
AB - The crystal structure of Saccharomyces cerevisiae cytoplasmic aspartate
aminotransferase (EC 2.6.1.1) has been determined to 2.05 A resolution in the
presence of the cofactor pyridoxal-5'-phosphate and the competitive inhibitor
maleate. The structure was solved by the method of molecular replacement. The
final value of the crystallographic R-factor after refinement was 23.1% with good
geometry of the final model. The yeast cytoplasmic enzyme is a homodimer with two
identical active sites containing residues from each subunit. It is found in the
"closed" conformation with a bound maleate inhibitor in each active site. It
shares the same three-dimensional fold and active site residues as the aspartate
aminotransferases from Escherichia coli, chicken cytoplasm, and chicken
mitochondria, although it shares less than 50% sequence identity with any of
them. The availability of four similar enzyme structures from distant regions of
the evolutionary tree provides a measure of tolerated changes that can arise
during millions of years of evolution.
PMID- 9655343
TI - Study of a noncovalent trp repressor: DNA operator complex by electrospray
ionization time-of-flight mass spectrometry.
AB - Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS) has been
used to study noncovalent interactions between the trp apo-repressor (TrpR), its
co-repressor tryptophan and its specific operator DNA. In 5 mM ammonium acetate,
TrpR was detected as a partially unfolded monomer. In the presence of a 21-base
pair DNA possessing the two symmetrically arranged CTAG consensus sequences
required for specific TrpR binding, a homodimer-dsDNA complex with a 1:1
stoichiometry was observed. Co-repressor was not needed for the complex to form
under our experimental conditions. Collision induced dissociation (CID-MS)
revealed that this complex was very stable in the gas phase since dissociation
was achieved only at energies that also broke covalent bonds. We saw no evidence
for the presence of the six water molecules that mediate the interaction between
the protein and the DNA in the crystal structure. To check the binding
specificity of the TrpR for its target DNA, a competitive experiment was
undertaken: the protein was mixed with an equimolar amount of three different
DNAs in which the two CTAG sequences were separated by 2, 4, and 6 bp,
respectively. Only the DNA with the correct consensus spacing of 4 bp was able to
form stable interactions with TrpR. This experiment demonstrates the potential of
ESI-MS to test the sequence-specificity of protein-DNA complexes. The
interactions between the TrpR-DNA complex and 5-methyl-, L- and D-tryptophan were
also investigated. Two molecules of 5-methyl- or L-tryptophan were bound with
high affinity to the TrpR-DNA complex. On the other hand, D-tryptophan appeared
to bind to the complex with poor specificity and poor affinity.
PMID- 9655344
TI - Excluded volume in the configurational distribution of a strongly-denatured
protein.
AB - The configurational distribution of phosphoglycerate kinase (PGK) strongly
denatured in 4 M guanidine hydrochloride solution is investigated using small
angle neutron scattering (SANS) and Monte Carlo computer simulation. It is shown
that the experimental scattering profile can be represented by a random flexible
chain of spheres of excess scattering density with excluded volume interactions,
the best agreement being achieved when partial sphere intersection is allowed.
The radius of gyration of the chain increases by a factor of 4 on denaturation,
whereas the average length of segments approximately 5 residues long increases by
only approximately 10%, consistent with a picture in which the large expansion on
denaturation originates primarily from increased long-range flexibility of the
polypeptide chain. The results provide a description of the chain statistics from
which the construction of starting points for simulation studies of folding of
the protein can be envisaged.
PMID- 9655345
TI - From coiled coils to small globular proteins: design of a native-like three-helix
bundle.
AB - A monomolecular native-like three-helix bundle has been designed in an iterative
process, beginning with a peptide that noncooperatively assembled into an
antiparallel three-helix bundle. Three versions of the protein were designed in
which specific interactions were incrementally added. The hydrodynamic and
spectroscopic properties of the proteins were examined by size exclusion
chromatography, sedimentation equilibrium, fluorescence spectroscopy, and NMR.
The thermodynamics of folding were evaluated by monitoring the thermal and
guanidine-induced unfolding transitions using far UV circular dichroism
spectroscopy. The attainment of a unique, native-like state was achieved through
the introduction of: (1) helix capping interactions; (2) electrostatic
interactions between partially exposed charged residues; (3) a diverse collection
of apolar side chains within the hydrophobic core.
PMID- 9655346
TI - Design, total synthesis, and functional overexpression of the Candida rugosa lip1
gene coding for a major industrial lipase.
AB - The dimorphic yeast Candida rugosa has an unusual codon usage that hampers the
functional expression of genes derived from this yeast in a conventional
heterologous host. Commercial samples of C. rugosa lipase (CRL) are widely used
in industry, but contain several different isoforms encoded by the lip gene
family, among which the isoform encoded by the gene lip1 is the most prominent.
In a first laborious attempt, the lip1 gene was systematically modified by site
directed mutagenesis to gain functional expression in Saccharomyces cerevisiae.
As alternative approach, the gene (1647 bp) was completely synthesized with an
optimized nucleotide sequence in terms of heterologous expression in yeast and
simplified genetic manipulation. The synthetic gene was functionally expressed in
both hosts S. cerevisiae and Pichia pastoris, and the effect of heterologous
leader sequences on expression and secretion was investigated. In particular,
using P. pastoris cells, the synthetic gene was functionally overexpressed,
allowing for the first time to produce recombinant Lipl of high purity at a level
of 150 U/mL culture medium. The physicochemical and catalytic properties of the
recombinant lipase were compared with those of a commercial, nonrecombinant C.
rugosa lipase preparation containing lipase isoforms.
PMID- 9655347
TI - Electrospray-ionization mass spectrometry of intact intrinsic membrane proteins.
AB - Membrane proteins drive and mediate many essential cellular processes making them
a vital section of the proteome. However, the amphipathic nature of these
molecules ensures their detailed structural analysis remains challenging. A
versatile procedure for effective electrospray-ionization mass spectrometry (ESI
MS) of intact intrinsic membrane proteins purified using reverse-phase
chromatography in aqueous formic acid/isopropanol is presented. The spectra of
four examples, bacteriorhodopsin and its apoprotein from Halobacterium and the D1
and D2 reaction-center subunits from spinach thylakoids, achieve mass
measurements that are within 0.01% of calculated theoretical values. All of the
spectra reveal lesser quantities of other molecular species that can usually be
equated with covalently modified subpopulations of these proteins. Our analysis
of bovine rhodopsin, the first ESI-MS study of a G-protein coupled receptor,
yielded a complex spectrum indicative of extensive molecular heterogeneity. The
range of masses measured for the native molecule agrees well with the range
calculated based upon variable glycosylation and reveals further heterogeneity
arising from other covalent modifications. The technique described represents the
most precise way to catalogue membrane proteins and their post-translational
modifications. Resolution of the components of protein complexes provides
insights into native protein/protein interactions. The apparent retention of
structure by bacteriorhodopsin during the analysis raises the potential of
obtaining tertiary structure information using more developed ESI-MS experiments.
PMID- 9655348
TI - Fold prediction by a hierarchy of sequence, threading, and modeling methods.
AB - Several fold recognition algorithms are compared to each other in terms of
prediction accuracy and significance. It is shown that on standard benchmarks,
hybrid methods, which combine scoring based on sequence-sequence and sequence
structure matching, surpass both sequence and threading methods in the number of
accurate predictions. However, the sequence similarity contributes most to the
prediction accuracy. This strongly argues that most examples of apparently
nonhomologous proteins with similar folds are actually related by evolution.
While disappointing from the perspective of the fundamental understanding of
protein folding, this adds a new significance to fold recognition methods as a
possible first step in function prediction. Despite hybrid methods being more
accurate at fold prediction than either the sequence or threading methods, each
of the methods is correct in some cases where others have failed. This partly
reflects a different perspective on sequence/structure relationship embedded in
various methods. To combine predictions from different methods, estimates of
significance of predictions are made for all methods. With the help of such
estimates, it is possible to develop a "jury" method, which has accuracy higher
than any of the single methods. Finally, building full three-dimensional models
for all top predictions helps to eliminate possible false positives where
alignments, which are optimal in the one-dimensional sequences, lead to
unsolvable sterical conflicts for the full three-dimensional models.
PMID- 9655349
TI - Formation and properties of mixed disulfides between thioredoxin reductase from
Escherichia coli and thioredoxin: evidence that cysteine-138 functions to
initiate dithiol-disulfide interchange and to accept the reducing equivalent from
reduced flavin.
AB - Mutation of one of the cysteine residues in the redox active disulfide of
thioredoxin reductase from Escherichia coli results in C135S with Cys138
remaining or C138S with Cys135 remaining. The expression system for the genes
encoding thioredoxin reductase, wild-type enzyme, C135S, and C138S has been re
engineered to allow for greater yields of protein. Wild-type enzyme and C135S
were found to be as previously reported, whereas discrepancies were detected in
the characteristics of C138S. It was shown that the original C138S was a
heterogeneous mixture containing C138S and wild-type enzyme and that enzyme
obtained from the new expression system is the correct species. C138S obtained
from the new expression system having 0.1% activity and 7% flavin fluorescence of
wild-type enzyme was used in this study. Reductive titrations show that, as
expected, only 1 mol of sodium dithionite/mol of FAD is required to reduce C138S.
The remaining thiol in C135S and C138S has been reacted with 5,5'-dithiobis-(2
nitrobenzoic acid) to form mixed disulfides. The half time of the reaction was <5
s for Cys138 in C135S and approximately 300 s for Cys135 in C138S showing that
Cys138 is much more reactive. The resulting mixed disulfides have been reacted
with Cys32 in C35S mutant thioredoxin to form stable, covalent adducts C138S-C35S
and C135S-C35S. The half times show that Cys138 is approximately fourfold more
susceptible to attack by the nucleophile. These results suggest that Cys138 may
be the thiol initiating dithiol-disulfide interchange between thioredoxin
reductase and thioredoxin.
PMID- 9655350
TI - In vivo acetylation identified at lysine 70 of human lens alphaA-crystallin.
AB - Posttranslational modification of protein lysyl residues that change the net
charge of the molecule may alter the protein conformation. Such modifications are
of particular significance among lens proteins, because conformational changes
are associated with the development of cataract. A previously unidentified
acetylated form of alphaA-crystallin has been isolated from the water-soluble
portion of human lenses. The alphaA-crystallins were fractionated by anion
exchange HPLC into seven peaks, each containing more than one form of alphaA
crystallin. The previously reported deamidated and phosphorylated forms were
identified by their molecular masses, determined by electrospray ionization mass
spectrometry. In addition to these modifications, approximately 5% of alphaA
crystallin had a modification that decreased the charge by one and increased the
molecular mass by 42 u. This modification, identified as acetylation, was located
uniquely at Lys 70. Like any modification that alters the surface charge,
acetylation may affect protein conformation and intermolecular interactions,
thereby altering the solubility or chaperone properties of alphaA-crystallin.
Acetylation of lysine 70 is potentially significant since it is located in a
region that has been implicated in the chaperone activity of alphaA-crystallin.
PMID- 9655351
TI - Prediction of functional residues in water channels and related proteins.
AB - In this paper, we present an updated classification of the ubiquitous MIP (Major
Intrinsic Protein) family proteins, including 153 fully or partially sequenced
members available in public databases. Presently, about 30 of these proteins have
been functionally characterized, exhibiting essentially two distinct types of
channel properties: (1) specific water transport by the aquaporins, and (2) small
neutral solutes transport, such as glycerol by the glycerol facilitators.
Sequence alignments were used to predict amino acids and motifs discriminant in
channel specificity. The protein sequences were also analyzed using statistical
tools (comparisons of means and correspondence analysis). Five key positions were
clearly identified where the residues are specific for each functional subgroup
and exhibit high dissimilar physico-chemical properties. Moreover, we have found
that the putative channels for small neutral solutes clearly differ from the
aquaporins by the amino acid content and the length of predicted loop regions,
suggesting a substrate filter function for these loops. From these results, we
propose a signature pattern for water transport.
PMID- 9655352
TI - Guanidine hydrochloride unfolding of a transmembrane beta-strand in FepA using
site-directed spin labeling.
AB - We have used the electron spin resonance (ESR) site-directed spin-labeling (SDSL)
technique to examine the guanidine hydrochloride (Gdn-HCl) induced denaturation
of several sites along a transmembrane beta-strand located in the ferric
enterobactin receptor, FepA. In addition, we have continued the characterization
of the beta-strand previously identified by our group (Klug CS et al., 1997,
Biochemistry 36:13027-13033) to extend from the periplasm to the extracellular
surface loop in FepA, an integral membrane protein containing a beta-barrel motif
comprised of a series of antiparallel beta-strands that is responsible for
transport of the iron chelate, ferric enterobactin (FeEnt), across the outer
membrane of Escherichia coli and many related enteric bacteria. We have
previously shown that a large surface loop in FepA containing the FeEnt binding
site denatures independently of the beta-barrel domain (Klug CS et al., 1995,
Biochemistry 34:14230-14236). The SDSL approach allows examination of the
unfolding at individual residues independent of the global unfolding of the
protein. This work shows that sites along the beta-strand that are exposed to the
aqueous lumen of the channel denature more rapidly and with higher cooperativity
than the surface loop, while sites on the hydrophobic side of the beta-strand
undergo a limited degree of noncooperative unfolding and do not fully denature
even at high (e.g., 4 M) Gdn-HCl concentrations. We conclude that, in a
transmembrane beta-strand, the local environment of a given residue plays a
significant role in the loss of structure at each site.
PMID- 9655353
TI - Structure and distribution of pentapeptide repeats in bacteria.
AB - We report the discovery of a novel family of proteins, each member contains
tandem pentapeptide (five residue) repeats, described by the motif A(D/N)LXX.
Members of this family are both membrane bound and cytoplasmic. The function of
these repeats is uncertain, but they may have a targeting or structural function
rather than enzymatic activity. This family is most common in cyanobacteria,
suggesting a function related to cyanobacterial-specific metabolism. Although no
experimental information is available for the structure of this family, it is
predicted that the tandem pentapeptide repeats will form a right-handed beta
helical structure. A structural model of the pentapeptide repeats is presented.
PMID- 9655354
TI - Developmental changes in carbonic anhydrase II in the rat kidney.
AB - We examined the distribution and maturational changes of carbonic anhydrase I
(CAI) and carbonic anhydrase II (CAII) in microdissected nephron segments of
Sprague-Dawley rats. CAI and CAII proteins were measured by enzyme-linked
immunosorbent assay. CAI was not detected in any nephron segment in 7-week-old
rats. CAII was present in the collecting ducts, proximal tubules, and thick
ascending limbs of loop of Henle in 7-week-old rats. CAII contents were
significantly higher in the early proximal tubules (S1) than in second (S2) and
late (S3) portions of the proximal tubules, while the contents in S1 were less
than in cortical collecting ducts (CCD), outer stripe and inner stripes of the
outer medullary collecting ducts (OMCDo and OMCDi). CAII content in each of S1,
CCD, and OMCD of 1-week-old rats was only 14% or less of that of adults, but
increased steeply during the 2nd and 3rd weeks of life, reaching almost 40% at 3
weeks of age and 97% at 7 weeks. Our results indicate that CAII is present
throughout the entire nephron of the rat, and that CAII content in S1, CCD, and
OMCD increases exponentially during the first 7 weeks of life. Our data suggest
that the immature low levels of CAII may explain, at least in part, the limited
capacity of urinary acidification during neonatal life. Further studies are
necessary to establish the role of such changes in CAII content in acid-base
homeostasis during neonatal life.
PMID- 9655355
TI - Chronology of renal scarring in males with Alport syndrome.
AB - We investigated the onset of renal scarring in 62 males (aged 4-26 years) with
Alport syndrome by measuring cortical interstitial volume fraction [Vv
(interstitium/cortex)] and percentage global glomerular sclerosis in kidney
biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as
controls. Creatinine clearance at the time of biopsy was available for 43 Alport
patients. A statistically insignificant correlation between age and Vv
(interstitium/cortex) was observed in normal subjects (r = +0.47, slope = 0.0009,
P = 0.07). In the Alport patients, age was significantly correlated with Vv
(interstitium/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular
sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine
clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated
with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular
sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was
especially strong for Vv (interstitium/cortex) values above the normal range,
i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) <
0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per
1.73 m2 occurred more frequently in patients with Vv (interstitium/cortex) values
> 0.2 (P < 0.0001) and in patients with > 10% globally sclerosed glomeruli (P <
0.001). Patients < or = or > 10 years of age differed in Vv (interstitium/cortex)
[0.13 +/- 0.09 (mean +/- SD) vs. 0.24 +/- 0.026, P < 0.001], the frequency of Vv
(interstitium/cortex) > 0.2 (3/32 vs. 15/31, P < 0.0001), the frequency of > 10%
globally sclerosed glomeruli (3/33 vs. 11/30, P < 0.05), mean creatinine
clearance (113 +/- 7 vs. 84 +/- 10 ml/min per 1.73 m2, P = 0.057), and the
frequency of creatinine clearance < 80 ml/min per 1.73 m2 (1/20 vs. 11/23, P <
0.01). Thus, reduced creatinine clearance in males with Alport syndrome is
associated with Vv (interstitium/cortex) > 0.2 and > 10% globally sclerosed
glomeruli. These are frequently detectable in the 2nd decade. We hypothesize that
most Alport males will require intervention during the 1st decade for optimal
preservation of kidney function.
PMID- 9655356
TI - Urinary excretion substances in patients with cystic fibrosis: risk of
urolithiasis?
AB - Patients with cystic fibrosis (CF) have an increased risk of
urolithiasis/nephrocalcinosis. To determine potential mechanisms responsible, we
studied the urinary excretion of lithogenic and stone-inhibitory substances and
calculated the urinary saturation for calcium-oxalate (CaOx), brushite (CaHPO4),
and uric acid (UA). We examined 24-h urines in 63 patients with CF (34 female, 29
male) aged 5 months to 36 years. Renal ultrasonography was performed at the time
of urine collection. Hyperoxaluria was found in 25 patients (range 0.51-1.71
mmol/1.73 m2 per 24 h). Urinary Ca was increased in 13 patients (4.1-8.22 mg/kg
per 24 h). Hyperuricosuria was found in 16 patients (5.2-18.0 mmol/1.73 m2 per 24
h) and hypocitraturia in 14 patients (0.07-1.14 mmol/1.73 m2 per 24 h). CaOx
saturation was elevated in 26 patients, related to hyperoxaluria in 19 patients.
CaHPO4 saturation was increased in 19 patients and UA saturation in 11 patients.
Urolithiasis in situ was diagnosed in 1 patient; 3 patients previously had renal
stones; 4 patients had present nephrocalcinosis. Elevated excretion of lithogenic
substances and urinary supersaturation might lead to the higher risk of
urolithiasis/nephrocalcinosis in patients with CF.
PMID- 9655357
TI - Renal tubular function in beta-thalassemia.
AB - Studies of the renal involvement in thalassemic syndromes have been varied and
few. This study was designed to define the renal abnormalities associated with
beta-thalassemia and to correlate the renal findings with clinical parameters.
One hundred and four beta-thalassemic children with various disease severity were
studied. The patients were divided into three groups: 48 with severe anemia
[hematocrit (Hct) < 25%], 31 on a hypertransfusion program and desferrioxamine
treatment, and 25 with moderate anemia (Hct > 25%). The results were compared
with 15 normal children. Significantly higher levels of proteinuria and low
molecular weight proteinuria were found in all patients compared with normal
children. Aminoaciduria was detected in one-third of patients. Thalassemic
patients had significantly lower morning urine osmolarity, higher urine N-acetyl
beta-D-glucoseminidase and malondialdehyde (MDA, an indicator of lipid
peroxidation). Patients with severe anemia had significantly higher low-molecular
weight proteinuria and MDA, and lower urine osmolarity than those with moderate
anemia. Our data confirmed the high frequency of renal abnormalities in beta
thalassemia patients and indicated some degree of proximal tubular dysfunction.
Severity of the abnormalities correlated with the degree of anemia and were least
severe in patients on hypertransfusion and desferrioxamine therapy. This
suggested that the damage might be caused by anemia and increased oxidation
induced by excess iron deposits.
PMID- 9655358
TI - Vincristine and focal segmental sclerosis: do we need a multicentre trial?
AB - Over the last 10 years, eight children have received vincristine for the
treatment of steroid- and cyclophosphamide-resistant nephrotic syndrome at Great
Ormond Street Hospital for Children, London. We present our experience of these
eight cases and put forward a case for reassessing the effectiveness of
vincristine in this disorder. In our series, two children treated with
vincristine achieved complete remission with preserved renal function, including
relapses in one. Both had primary steroid- and cyclophosphamide-resistant focal
segmental glomerulo sclerosis (FSGS). Of the other cases, four also had primary
FSGS, one familial FSGS and one mesangioproliferative glomerulonephritis. We
discuss in general the pros and cons of vincristine therapy in nephrotic syndrome
versus the cytotoxic agents that are currently used and the differences in
clinical features among the responders and non-responders in this small group. In
addition, we explore why this may have occurred and summarise the literature over
the last 25 years, where vincristine appeared to have been beneficial, especially
in secondary forms of nephrotic syndrome associated with malignancy. We conclude
that vincristine therapy warrants re-examination as it could be a valuable
alternative therapeutic agent in some cases of FSGS with relatively minor side
effects.
PMID- 9655359
TI - Albumin, IgG, retinol-binding protein, and alpha1-microglobulin excretion in
childhood.
AB - Urine concentrations of two high molecular weight proteins, albumin and IgG, and
two low molecular weight proteins, alpha1-microglobulin (A1M) and retinol-binding
protein (RBP), were measured in 657 healthy children from birth to 18 years of
age. The urinary levels of RBP and A1M suggest an age-dependent decline, whereas
the levels of albumin and IgG show an uneven distribution. Reference values for
albumin, IgG, A1M, and RBP for each group are reported.
PMID- 9655360
TI - Successful renal transplantation in Jeune syndrome type 2.
AB - Jeune syndrome (asphyxiating thoracic dystrophy) is a rare inherited disease
which is fatal in early childhood in 70% of cases. Severe renal involvement may
occur and lead to chronic renal insufficiency in patients who survive respiratory
failure. Therefore the opportunity to perform kidney transplantation is quite
rare. We report a successful cadaver renal transplantation in a 10-year-old boy
with Jeune syndrome type 2.
PMID- 9655361
TI - Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children over 5
years.
AB - We retrospectively evaluated the frequency of renal scintigraphic abnormalities
in children over 5 years admitted with a first symptomatic urinary tract
infection (UTI). Among 261 children investigated, we found only 23 over 5 years
having had technetium-99m-dimercaptosuccinic acid scintigraphy during the acute
phase of a first UTI. Obvious scintigraphic abnormalities were detected in 14
children (15 kidneys): 12 kidneys showed focal cortical defects and 3 were small
and deformed. Ultrasound was normal in 7 of the 15 kidneys with abnormal
scintigraphy and in all the kidneys with normal scintigraphy. Among the 12
kidneys with focal cortical lesions, 8 kidneys returned to normal or improved
considerably 2-12 months after initial work-up. In conclusion, in children over 5
years admitted with a first symptomatic UTI, the frequency of scintigraphic
abnormalities is high and a strategy based only on ultrasound data would miss
about 50% of the abnormal kidneys.
PMID- 9655362
TI - Effect of hyperparathyroidism on response to erythropoietin in children on
dialysis.
AB - The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice
weekly, was studied prospectively in 17 children and adolescents with end-stage
renal disease who were either transfusion dependent or had hematocrits < 25%. For
convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and
subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure,
hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline
phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored
serially. When serum ferritin was < 100 ng/ ml during therapy, 6 patients
received iron supplementation. rHuEPO therapy eliminated frequent transfusions in
all patients; 11 of 17 patients reached the target hematocrit of 30%-33% by week
16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously
reached target at week 6 +/- 1; 6 HD patients treated intravenously reached
target at week 11 +/- 3; 6 additional HD patients never reached target at this
dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher
than those of the other patients (P < 0.005); 3 of 6 later reached a hematocrit
of 30%-33% after the rHuEPO dose was increased to 120-130 units/kg thrice weekly.
We conclude that most pediatric dialysis patients can be treated successfully
with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is
markedly elevated, in which case a higher dose is likely to be needed.
PMID- 9655363
TI - Recombinant human growth hormone treatment of children on hemodialysis. French
Society of Pediatric Nephrology.
AB - Forty-two children, aged 2-21.5 years on hemodialysis with a height below -2.0
standard deviation score (SDS) for age, were selected to receive recombinant
human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36
were prepubertal and 8 were in early puberty (testicular volume between 4 and 8
ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week
by daily subcutaneous injection for 1-5 years. The year before rhGH therapy
served as a control period. During the 1st year of treatment, mean growth
velocity increased from 3.5 to 7.0 cm/year (P < 0.0001) and was always over 2.5
cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither
weight nor the body mass index varied compared with the pretreatment year. No
change was observed in urea, creatinine, or glucose tolerance. The mean increment
in bone age was 0.9 years. The mean growth velocity decreased over subsequent
years (P < 0.0001), but remained higher than the prestudy velocity. A significant
negative correlation was observed during the 1st year between the increase in
growth velocity and the prestudy velocity (P < 0.0001), with the least gain in
patients who had the best spontaneous velocity. Pubertal status had no influence
on response to rhGH. No significant side effects were observed during the 103
treatment-years. Five patients developed secondary hyperparathyroidism and 1
suffered from acute pancreatitis, but the relationship with rhGH therapy remains
uncertain. rhGH therapy appears indicated for children on hemodialysis, even
though the potential benefits appear somewhat lower for those with a spontaneous
growth velocity over 6 cm/year.
PMID- 9655364
TI - Effect of posture on intraperitoneal pressure and peritoneal permeability in
children.
AB - The posture of the patient influences both the intraperitoneal pressure (IPP) and
the peritoneal permeability. We have studied the effects of the supine and the
upright position in six children. Two peritoneal equilibration tests (PET) of 90
min dwell time each were performed consecutively, firstly in the supine position
and then in the upright position. The same amount of dialysate was instilled
(1,000 ml/m2; isotonic 1.36% dextrose) for each PET. Using the same filling
volume, the IPP was significantly higher in the upright position (18.4 +/- 4.8 cm
H2O) than in the supine position (8 +/- 2.4 cm H2O). The mean percentage IPP
increase was 130% +/- 35%. The decline in glucose resorption rate from the
dialysate during the PET was significantly lower in the upright position. Despite
this greater relative loss of osmotic gradient in the upright than the supine
position, no significant difference in net ultrafiltration was noted after 90 min
of dwell. The peritoneal equilibration ratio during the PET was lower in the
upright than the supine position for urea, creatinine, and phosphate. These
results favor performing peritoneal dialysis in a supine position, both to
increase dialysis efficiency and to reduce patient discomfort.
PMID- 9655365
TI - Bartter and related syndromes: the puzzle is almost solved.
AB - It is now evident that the term Bartter syndrome does not represent a unique
entity but encompasses a variety of disorders of renal electrolyte transport.
Application of molecular biology techniques has permitted a better understanding
of these "Bartter-like syndromes," which at present can be divided into three
different genetic and clinical entities. Neonatal Bartter syndrome is observed in
newborn infants and characterized by polyhydramnios, premature delivery, life
threatening episodes of fever and dehydration during the early weeks of life,
growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Two
molecular defects have been identified: either at the gene encoding the renal
bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP
sensitive inwardly rectifying K channel (ROMK). "Classic" Bartter syndrome is
mostly observed during infancy and childhood and is characterized clinically by
polyuria and growth retardation. Nephrocalcinosis is not present. Very recently,
either deletions or mutations at the gene encoding a renal chloride channel (ClC
Kb) have been identified. Gitelman syndrome is observed in older children and
adults presenting with intermittent episodes of muscle weakness and tetany,
hypokalemia, and hypomagnesemia. Mutations at the gene encoding the thiazide
sensitive Na-Cl cotransporter have been identified in the majority of patients
studied. Obviously the validity of this classification must be confirmed in the
near future when all mutations have been described and genotypic-phenotypic
correlations are better defined.
PMID- 9655366
TI - Chronic renal insufficiency in children and adolescents: the 1996 annual report
of NAPRTCS. North American Pediatric Renal Transplant Cooperative Study.
AB - The 1996 annual report of the Chronic Renal Insufficiency Arm of the North
American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes
descriptive data and highlights important features on 1,725 patients from 130
centers. This database contains information on patients with an estimated
glomerular filtration rate (GFR) < or = 75 ml/min per 1.73 m2 as calculated by
the Schwartz formula, who were treated on or after 1 January 1994. Thus this
report reflects 2 years of data entry. Analysis of the data revealed that nearly
two-thirds of patients registered had a structural anomaly. On average, patients
were 1.5 standard deviations below age- and sex-specific norms for height, and
0.6 standard deviations below weight norms. Mean serum creatinine for the entire
group was 2.4 mg/dl and 68% of patients had a baseline GFR of at least 25 ml/min
per 1.73 m2. The mean hematocrit for all children at registration was 33.3 +/-
6.3%, and did not vary among age groups. Overall, 30.9% of patients had a
hematocrit < 30%. Only 12.8% of patients were receiving Epoetin therapy. Although
still in infancy, the Chronic Renal Insufficiency Arm of the NAPRTCS database in
providing important insights into this disorder.
PMID- 9655367
TI - Investigation of girls with urinary tract infection.
PMID- 9655368
TI - Chronic renal insufficiency and recombinant human growth hormone treatment.
PMID- 9655369
TI - Distributions of conjugated linoleic acid (CLA) isomers in tissue lipid classes
of pigs fed a commercial CLA mixture determined by gas chromatography and silver
ion-high-performance liquid chromatography.
AB - Pigs were fed a commercial conjugated linoleic acid (CLA) mixture, prepared by
alkali isomerization of sunflower oil, at 2% of the basal diet, from 61.5 to 106
kg live weight, and were compared to pigs fed the same basal diet with 2% added
sunflower oil. The total lipids from liver, heart, inner back fat, and omental
fat of pigs fed the CLA diet were analyzed for the incorporation of CLA isomers
into all the tissue lipid classes. A total of 10 lipid classes were isolated by
three-directional thin-layer chromatography and analyzed by gas chromatography
(GC) on long capillary columns and by silver-ion high-performance liquid
chromatography (Ag+-HPLC); cholesterol was determined spectrophotometrically.
Only trace amounts (<0.1%; by GC) of the 9,11-18:2 cis/trans and trans,trans
isomers were observed in pigs fed the control diet. Ten and twelve CLA isomers in
the diet and in pig tissue lipids were separated by GC and Ag+- HPLC,
respectively. The relative concentration of all the CLA isomers in the different
lipid classes ranged from 1 to 6% of the total fatty acids. The four major
cis/trans isomers (18.9% 11 cis,13 trans-18:2; 26.3% 10 trans,12 cis-18:2; 20.4%
9 cis,11 trans-18:2; and 16.1% 8 trans, 10 cis-18:2) constituted 82% of the total
CLA isomers in the dietary CLA mixture, and smaller amounts of the corresponding
cis,cis (7.4%) and trans,trans (10.1%) isomers were present. The distribution of
CLA isomers in inner back fat and in omental fat of the pigs was similar to that
found in the diet. The liver triacylglycerols (TAG), free fatty acids (FFA), and
cholesteryl esters showed a similar pattern to that found in the diet. The major
liver phospholipids showed a marked increase of 9 cis,11 trans-18:2, ranging from
36 to 54%, compared to that present in the diet. However, liver
diphosphatidylglycerol (DPG) showed a high incorporation of the 11 cis,13 trans
18:2 isomer (43%). All heart lipid classes, except TAG, showed a high content of
11 cis,13 trans-18:2, which was in marked contrast to results in the liver. The
relative proportion of 11 cis,13 trans-18:2 ranged from 30% in the FFA to 77% in
DPG. The second major isomer in all heart lipids was 9 cis,11 trans-18:2. In both
liver and heart lipids the relative proportions of both 10 trans,12 cis-18:2 and
8 trans, 10 cis-18:2 were significantly lower compared to that found in the diet.
The FFA in liver and heart showed the highest content of trans,trans isomers (31
to 36%) among all the lipid classes. The preferential accumulation of the 11
cis,13 trans-18:2 into cardiac lipids, and in particular the major phospholipid
in the inner mitochondrial membrane, DPG, in both heart and liver, appears unique
and may be of concern. The levels of 11 cis,13 trans-18:2 naturally found in
foods have not been established.
PMID- 9655370
TI - Dietary docosahexaenoic acid and immunocompetence in young healthy men.
AB - The purpose of this study was to examine the effect of dietary docosahexaenoic
acid (DHA), in the absence of eicosapentaenoic acid, on human immune response
(IR). A 120-d study with 11 healthy men was conducted at the Metabolic Research
Unit of the Western Human Nutrition Research Center. Four subjects (control
group) were fed the stabilization or basal diet (15, 30, and 55% energy from
protein, fat, and carbohydrate, respectively) throughout the study; the remaining
seven subjects (DHA group) were fed the basal diet for the first 30 d, followed
by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic
acid; the two diets were comparable in their total fat and all other nutrients.
Both diets were supplemented with 20 mg d-alpha-tocopherol acetate per day.
Indices of IR were examined on study day 22, 30, 78, 85, 106, and 113. Addition
of DHA at moderately high levels did not alter the proliferation of peripheral
blood mononuclear cells cultured with phytohemagglutinin or concanavalin A, or
the delayed hypersensitivity skin response. Also, additional DHA did not alter
the number of T cells producing interleukin 2 (IL2), the ratio between the
helper/suppressor T cells in circulation, or the serum concentrations of
immunoglobulin G, C3, and interleukin 2 receptor (IL2R). DHA supplementation,
however, caused a significant (P = 0.0001) decrease in the number of circulating
white blood cells which was mainly due to a decrease in the number of circulating
granulocytes. The number of lymphocytes in peripheral circulation was not
affected by Dietary DHA enrichment, but the percentage of lymphocytes in white
blood cells increased because of a reduction in granulocyte numbers. None of
these indices was changed in the control group. Our results show that when total
fat intake is low and held constant, DHA consumption does not inhibit many of the
lymphocyte functions which have been reported to be inhibited by fish oil
consumption.
PMID- 9655371
TI - The metabolism and n-6/n-3 ratio of essential fatty acids in rats: effect of
dietary arachidonic acid and a mixture of sesame lignans (sesamin and
episesamin).
AB - In this study, we examined the effect of dietary arachidonic acid (AA) and sesame
lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in
rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum.
For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet
groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil
group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and
AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame
lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3
ratio in the liver were significantly increased in the AO group, despite the
dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA
content and n-6/n-3 ratio to a level similar to the CO and COS groups. These
results suggest that (i) dietary AA considerably affects the hepatic profile and
n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n
6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was
significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was
decreased. On the other hand, the AO diet increased the concentration of TG in
serum by almost twofold as compared to other groups. However, the AOS diet
significantly reduced serum TG level as compared to the AO group. In addition,
the AOS diet significantly increased the acetoacetate level, but reduced the beta
hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame
lignans promote ketogenesis and reduce PUFA esterification into TG. This study
resulted in two findings: (i) sesame lignans inhibited extreme changes of the n
6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic
PUFA content may have occurred because of the effects of sesame lignans on PUFA
degradation (oxidation) and esterification.
PMID- 9655372
TI - Psyllium, not pectin or guar gum, alters lipoprotein and biliary bile acid
composition and fecal sterol excretion in the hamster.
AB - Different soluble dietary fibers known to alter cholesterol metabolism were fed
to golden Syrian hamsters, and their specific impact on lipoproteins, biliary
bile acid profile, and fecal sterol excretion was evaluated. Semipurified diets
containing 20% fat; 0.12% cholesterol; and 8% of psyllium (PSY); high (hePE) and
low (lePE) esterified pectin; or high (hvGG) and low (lvGG) viscous guar gum were
fed for 5 wk. Compared to control, PSY caused a significant reduction in plasma
cholesterol (2.9 +/- 0.5 vs. 5.5 +/- 0.5 mmol/L), whereas hePE, lePE, hvGG, or
lvGG had no apparent effect on plasma lipids. Hepatic total and esterified
cholesterol were substantially decreased with PSY, pectin and guar gum, whereby
PSY produced the most pronounced effect. Distinctive changes existed in the bile
acid profile related to the different fibers. In contrast to pectin and guar gum,
PSY caused a significant increase in the cholate:chenodeoxycholate and the
glycine:taurine conjugation ratio. Pectin and guar gum did not alter daily fecal
neutral sterol excretion while PSY caused a 90% increase due to a higher fecal
output. Daily fecal bile acid excretion and total fecal bile acid concentration
were significantly increased by PSY, whereas hePE, lePE, hvGG, and lvGG revealed
no or only minor effects. Taken together, the disparate hypocholesterolemic
effects of PSY, pectin, and guar gum on cholesterol and bile acid metabolism in
the hamster are possibly related to different physicochemical properties, e.g.,
viscosity and susceptibility to fermentation, affecting the fiber-mediated action
in the intestine.
PMID- 9655374
TI - Protective effect of a vitamin E analog, phosphatidylchromanol, against oxidative
hemolysis of human erythrocytes.
AB - The protective effect of a vitamin E analog, phosphatidylchromanol [1,2-diacyl-sn
glycero-3-phospho-2'-(hydroxyethyl)-2',5',7',8'-tetrameth yl-6'-hydroxychroman;
PCh], against oxidative hemolysis of human erythrocytes was examined and was
compared with those of vitamin E (alpha-tocopherol) and 2,2,5,7,8-pentamethyl-6
chromanol (PMC). These three compounds at 50 microM protected the erythrocytes
from hemolysis, when erythrocyte suspension (10%, vol/vol) was incubated with a
water-soluble radical generator, 2,2'-azobis(2-amidinopropane)-dihydrochloride
(75 mM). When erythrocyte suspension was oxidized after pretreatment with these
compounds (50 microM) for 30 min followed by washing, PCh protected about 54% of
erythrocytes from the hemolysis, while alpha-tocopherol protected only about 16%
of the cells and PMC did not show any protective effect. During preincubation,
alpha-tocopherol, PMC, and PCh were incorporated into the cells at the
concentration of 12.6, 3.7, and 16.3 nmol/mg protein, respectively. Moreover, PCh
was found in the ghost membrane fraction at a 20% higher level than alpha
tocopherol, and no PMC was detected in this fraction. These results indicate that
phosphatidyl group in PCh acts as an excellent carrier of chromanol moiety into
cells as well as an anchor within membranes more efficiently than phytyl group in
alpha-tocopherol. PMC seems to be slightly anchored within membranes because of
the lack of hydrophobic side chain. The excellent antihemolytic activity of PCh
is likely to be caused by its accumulation within erythrocyte membranes.
PMID- 9655373
TI - Dietary cyanidin 3-O-beta-D-glucoside increases ex vivo oxidation resistance of
serum in rats.
AB - The effect of dietary cyanidin 3-O-beta-D-glucoside (C3G), a typical anthocyanin
pigment, on the generation of thiobarbituric acid reactive substances (TBARS)
during serum formation ex vivo and susceptibility of serum to further lipid
peroxidation was studied in rats. Rats were fed a diet containing C3G (2 g/kg)
for 14 d. Feeding C3G resulted in a significant decrease in generation of TBARS
during serum formation. The serum from the C3G-fed group showed a significantly
lower susceptibility to further lipid peroxidation provoked by 2,2'-azobis(2
amidinopropane)hydrochloride or Cu2+ than that of the control group. No
significant differences were observed in serum phospholipid, triglyceride,
esterified cholesterol, and free fatty acid concentrations between the control
and the C3G-fed groups. Concentrations of endogenous antioxidants remaining in
the serum after blood coagulation were not affected by the C3G feeding. These
results demonstrate that feeding C3G increases the ex vivo oxidation resistance
of the serum without affecting serum endogenous antioxidant levels, and reduces
the TBARS generated during serum formation without changing the concentrations of
serum lipids.
PMID- 9655375
TI - Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous
micelles. II. Effect of antioxidants.
AB - We have reported that the peroxyl radicals derived from methyl eicosapentaenoate
(20:5n-3) are more polar than those from methyl linoleate (18:2n-6) since the
former peroxyl radicals have at least two molecules of oxygen in a molecule while
the latter peroxyl radical has one. This lowers the oxidizability for 20:5n-3 in
aqueous Triton X-100 micelles by enhancing the termination reaction rate for
peroxyl radicals and by reducing the rate of propagation since there may be more
polar peroxyl radicals derived from 20:5n-3 at the surface than within the
micelle core. In this study, we measured the effect of three antioxidants, di
tert-butyl-4-methylphenol (BHT), 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2
carboxy-2,5,7,8-tetramethyl-6-chromanol (Trolox), on the oxidation of lipids in
aqueous micelle. Antioxidants give a clear induction period during oxidation of
18:2n-6 initiated with a water-soluble radical initiator, and its induction
length decreases in the order of BHT > PMC > Trolox. This is consistent with the
proposed location of three antioxidants: being in the core of micelle, at the
surface, or in aqueous phase, respectively. However, BHT does not inhibit the
oxidation of 20:5n-3 efficiently, and its rate of oxidation is slower than that
observed in the oxidation of 18:2n-6, supporting the idea that polar peroxyl
radicals derived from 20:5n-3 are preferentially located at the surface of the
micelle. Similar results were obtained when oxidation was initiated with a lipid
soluble radical initiator except antioxidants had lesser effect on the oxidation
rate of 20:5n-3.
PMID- 9655376
TI - Partial purification and characterization of sphingosine N-acyltransferase
(ceramide synthase) from bovine liver mitochondrion-rich fraction.
AB - Sphingosine N-acyltransferase (ceramide synthase, E.C. 2.3.1.24) was solubilized
from bovine liver mitochondrion-rich fraction with n-octyl beta-D-thioglucoside
as the detergent and partially purified by sequential chromatography on columns
of DE-32, shingosine affinity, and Sepharose CL-6B. The partially purified
preparation migrated on SDS-polyacrylamide gel electrophoresis as two major
protein bands of 62 and 72 kDa. The molecular mass of the enzyme estimated by gel
filtration was 240-260 kDa, suggesting that the partially purified enzyme is
present in a subunit form or simply has an aggregative nature. The specific
activity of the final preparation for the condensation of sphingosine with
stearoyl-CoA increased by 98.7-fold compared with the starting material. The
optimal pH value for the ceramide synthesis was 7.5. The partially purified
enzyme had an apparent Km of 146 microM and a Vmax of 11.1 nmol/min/mg protein
for stearoyl-CoA. The Km and Vmax values toward sphingosine were 171 microM and
11.3 nmol/min/mg protein, respectively. Interestingly, sphinganine was also a
good substrate for this enzyme, and the Km and Vmax values were 144 microM and
8.5 nmol/min/mg protein, respectively.
PMID- 9655378
TI - Long-chain alkenes of the haptophytes Isochrysis galbana and Emiliania huxleyi.
AB - The major alkenes of the haptophytes Isochrysis galbana (strain CCAP 927/14) and
Emiliania huxleyi (strains CCAP 920/2 and VAN 556) have been identified by
nuclear magnetic resonance spectroscopy and by mass spectrometric analysis of
their dimethyl disulfide adducts. The dominant alkene in I. galbana is (22Z)-1
,22-hentriacontadiene, with 1,24-hentriacontadiene and 1,24-tritriacontadiene
present in much lower abundance; (22Z)-1,22-hentriacontadiene also occurs in E.
huxleyi (strain CCAP 920/2), together with (2Z,22Z)-2,22-hentriacontadliene (the
major hydrocarbon) and (3Z,22Z)-3,22-hentriacontadiene. Minor abundances of 2,24
hentriacontadiene and 2,24-tritriacontadiene are also present in this strain. In
contrast, the dominant alkene in E. huxleyi (strain VAN 556) is (15 E,22E)
1,16,23-heptatriacontatriene with the related alkatriene 1,15,22
octatriacontatriene also present and (22Z)-1,22-hentriacontadiene occurring as a
minor component. From structural relationships (15E,22E)-1,15,22
heptatriacontatriene is proposed to derive from the same biosynthetic pathway as
that of the characteristic C37 alkenones which occur in both E. huxleyi and I.
galbana. The C31 and C33 dienes likely derive from chain extension and
decarboxylation of (Z)-9-octadecenoic acid or (Z)-7-hexadecenoic acid, using a
pathway analogous to that elucidated previously in the chlorophyte Botryococcus
braunii. Therefore, long-chain dienes and trienes, which can co-occur in
haptophytes, may have distinct biosynthetic pathways.
PMID- 9655377
TI - N-stearoyl-phosphatidylserine: synthesis and role in divalent-cation-induced
aggregation and fusion.
AB - N-Acylphosphatidylserines have been isolated from intact and injured tissues, but
the participation of such acidic phospholipids in membrane aggregation and fusion
has not been demonstrated. We have synthesized N-stearoylphosphatidylserine
(NSPS) and examined divalent-cation-induced aggregation of NSPS-liposomes, which
leads to membrane destabilization and fusion. The purified lipid was
characterized by its chromatographic and spectroscopic (infrared and 1H nuclear
magnetic resonance) properties and by its chemical degradation pattern.
Aggregation of unilamellar NSPS-liposomes was studied as a function of calcium
and magnesium concentration. The ability of calcium and magnesium to induce
vesicle aggregation is higher for phosphatidylserine (PS)-liposomes (threshold
concentration 1.5 mM for calcium and 4.6 mM for magnesium) than for NSPS
liposomes (threshold concentration 2.8 mM for calcium and 6.6 mM for magnesium).
The irreversibility of the aggregation reactions after adding EDTA suggests that
vesicle fusion might occur in the presence of calcium and magnesium. Preliminary
studies, based on mixing of both lipid and internal aqueous contents, show that
fusion rather than aggregation of NSPS-liposomes occurs in the presence of
calcium ions. The tendency of NSPS-liposomes to aggregate at higher cation
concentrations than PS-liposomes suggests that N-acylation of phosphatidylserine
protects the membrane against degenerative damage caused by aggregation and
fusion.
PMID- 9655379
TI - Fatty acid composition of bacteria associated with the toxic dinoflagellate
Ostreopsis lenticularis and with Caribbean Palythoa species.
AB - The fatty acid composition of a Pseudomonas sp. (Alteromonas) and its host, the
dinoflagellate Ostreopsis lenticularis, vectors in ciguatera fish poisoning, has
been studied. The major fatty acids in O. lenticularis were 16:0, 20:5n-3, and
22:6n-3, but 18:2n-6, 18:3n-3, and 18:n-3 were also identified. In contrast to
other dinoflagellates, 1 8:5n-3 was not detected in O. lenticularis. Even-chain
fatty acids such as 9-16:1, 11-18:1, and 13-20:1 predominated in the Pseudomonas
sp. from O. lenticularis, but 1 6-20% of (E)-11-methyl-12-octadecenoic acid was
also identified. The chirality of the latter was confirmed by total synthesis
(28% overall yield) starting from oxacyclotridecan-2-one. The fatty acid
compositions of two other Pseudomonas species, from the palytoxin-producing
zoanthids Palythoa mamillosa and P. caribdea, were also studied and were similar
to that of the Pseudomonas sp. from O. lenticularis. The possibility of using
some of these fatty acids as chemotaxonomic lipids in identifying marine animals
that consume toxic dinoflagellates or zoanthids is discussed.
PMID- 9655380
TI - Epoxidation reactions of unsaturated fatty esters with potassium
peroxomonosulfate.
AB - Epoxidation of the double bond in methyl oleate, octadec-11E-en-9-ynoate,
ricinoleate (12-hydroxy-octadec-9Z-enoate), iso-ricinoleate (9-hydroxy-octadec
12Z-enoate), and 12-oxo-octadec-9Z-enoate with potassium peroxomonosulfate
(oxone, 2 KHSO5.KHSO4.K2SO4) in the presence of trifluoroacetone or methyl
pyruvate gave the corresponding monoepoxy derivatives. Reaction of Oxone with
methyl linoleate and octadeca-9Z,11E-dienoate furnished the corresponding
diepoxystearate derivative. Methyl 9,12-dioxo-octadec-10Z-enoate was obtained
when a C18 furanoid fatty ester (methyl 9,12-epoxy-9,11-octadecadienoate) was
treated with Oxone. The yield of these reactions was very high (85-99%), and the
epoxy derivatives were readily isolated by solvent extraction. The products were
identified by spectroscopic methods.
PMID- 9655381
TI - Callyspongynes A and B: new polyacetylenic lipids from a southern Australian
marine sponge, Callyspongia sp.
PMID- 9655382
TI - Journal prices lead libraries to back less costly initiatives.
PMID- 9655383
TI - Congress remains upbeat on public genome efforts.
PMID- 9655384
TI - South Africa's truth commission reveals bioweapons plot.
PMID- 9655385
TI - New voices displace east/west tensions.
PMID- 9655386
TI - Combinatorial chemistry in the hunt for medicines.
PMID- 9655387
TI - SMAD proteins and mammalian anatomy.
PMID- 9655388
TI - Actin, cofilin and cognition.
PMID- 9655389
TI - Deadly relic of the Great War.
PMID- 9655390
TI - Cnidarian homeoboxes and the zootype.
PMID- 9655391
TI - Nicotine metabolism defect reduces smoking.
PMID- 9655392
TI - Smad2 role in mesoderm formation, left-right patterning and craniofacial
development.
AB - Signalling by the transforming growth factor-beta (TGF-beta) superfamily of
proteins depends on the phosphorylation and activation of SMAD proteins by
heteromeric complexes of ligand-specific type I and type II receptors with
serine/threonine-kinase activity. The vertebrate SMAD family includes at least
nine members, of which Smad2 has been shown to mediate signalling by activin and
TGF-beta. In Xenopus, Smad2 can induce dorsal mesoderm, mimicking Vg-1, activin
and nodal. Here we investigate the function of Smad2 in mammalian development by
generating two independent Smad2 mutant alleles in mice by gene targeting. We
show that homozygous mutant embryos fail to form an organized egg cylinder and
lack mesoderm, like mutant mice lacking nodal or ActRIB, the gene encoding the
activin type-I receptor. About 20 per cent of Smad2 heterozygous embryos have
severe gastrulation defects and lack mandibles or eyes, indicating that the gene
dosage of Smad2 is critical for signalling. Mice trans-heterozygous for both
Smad2 and nodal mutations display a range of phenotypes, including gastrulation
defects, complex craniofacial abnormalities such as cyclopia, and defects in left
right patterning, indicating that Smad2 may mediate nodal signalling in these
developmental processes. Our results show that Smad2 function is essential for
early development and for several patterning processes in mice.
PMID- 9655393
TI - Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not
by PPARgamma activators.
AB - Peroxisome proliferator-activated receptors (PPARs) are key players in lipid and
glucose metabolism and are implicated in metabolic disorders predisposing to
atherosclerosis, such as dyslipidaemia and diabetes. Whereas PPARgamma promotes
lipid storage by regulating adipocyte differentiation, PPARalpha stimulates the
beta-oxidative degradation of fatty acids. PPARalpha-deficient mice show a
prolonged response to inflammatory stimuli, suggesting that PPARalpha is also a
modulator of inflammation. Hypolipidaemic fibrate drugs are PPARalpha ligands
that inhibit the progressive formation of atherosclerotic lesions, which involves
chronic inflammatory processes, even in the absence of their atherogenic
lipoprotein-lowering effect. Here we show that PPARalpha is expressed in human
aortic smooth-muscle cells, which participate in plaque formation and post
angioplasty re-stenosis. In these smooth-muscle cells, we find that PPARalpha
ligands, and not PPARgamma ligands, inhibit interleukin-1-induced production of
interleukin-6 and prostaglandin and expression of cyclooxygenase-2. This
inhibition of cyclooxygenase-2 induction occurs transcriptionally as a result of
PPARalpha repression of NF-kappaB signalling. In hyperlipidaemic patients,
fenofibrate treatment decreases the plasma concentrations of interleukin-6,
fibrinogen and C-reactive protein. We conclude that activators of PPARalpha
inhibit the inflammatory response of aortic smooth-muscle cells and decrease the
concentration of plasma acute-phase proteins, indicating that PPARalpha in the
vascular wall may influence the process of atherosclerosis and re-stenosis.
PMID- 9655394
TI - Modulation of AMPA receptor unitary conductance by synaptic activity.
AB - Activity-dependent alteration in synaptic strength is a fundamental property of
the vertebrate central nervous system and is thought to underlie learning and
memory. The most extensively studied model of activity-dependent synaptic
plasticity is long-term potentiation (LTP) of glutamate-responsive
(glutamatergic) synapses, a widespread phenomenon involving multiple mechanisms.
The best characterized form of LTP occurs in the CA1 region of the hippocampus,
in which LTP is initiated by transient activation of NMDA (N-methyl-D-aspartate)
receptors and is expressed as a persistent increase in synaptic transmission
through AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors.
This increase is due, at least in part, to a postsynaptic modification of AMPA
receptor function; this modification could be caused by an increase in the number
of receptors, their open probability, their kinetics or their single-channel
conductance. Here we show that the induction of LTP in the CA1 region of the
hippocampus is often associated with an increase in single-channel conductance of
AMPA receptors. This shows that elementary channel properties can be rapidly
modified by synaptic activity and provides an insight into one molecular
mechanism by which glutamatergic synapses can alter their strength.
PMID- 9655395
TI - IgD can largely substitute for loss of IgM function in B cells.
AB - The mu and delta heavy chains of IgM and IgD, the first antibody isotypes
expressed during bone-marrow B-cell development, are encoded by a common
transcription unit. Expression of the mu chain on the surface of late pre-B cells
allows their further development to immature B cells. Coexpression of the delta
chain and emigration of the immature B cells to the periphery eventually leads to
the development of naive mature IgM/IgD double-positive cells. Although IgM is
important in driving B-cell development, the contribution of IgD is not clear.
Here we investigate the function of IgD. We generated mice deficient in IgM (IgM
/- mice) by deleting the mu region in embryonic stem cells. IgM-/- mice showed
normal B-cell development and maturation, with IgD replacing membrane-bound and
secretory IgM. Moreover, specific B-cell responses and isotype class switches
occurred during immunization or infection. In contrast to mice deficient in B
cells, IgM-/- mice survived infection with vesicular stomatitis virus by
developing neutralizing immunoglobulins, but they were more susceptible than wild
type controls with delayed specific immunoglobulin responses. These data lead us
to conclude that IgD is largely able to substitute for IgM functions.
PMID- 9655396
TI - Evidence for the shikimate pathway in apicomplexan parasites.
AB - Parasites of the phylum Apicomplexa cause substantial morbidity, mortality and
economic losses, and new medicines to treat them are needed urgently. The
shikimate pathway is an attractive target for herbicides and antimicrobial agents
because it is essential in algae, higher plants, bacteria and fungi, but absent
from mammals. Here we present biochemical, genetic and chemotherapeutic evidence
for the presence of enzymes of the shikimate pathway in apicomplexan parasites.
In vitro growth of Toxoplasma gondii, Plasmodium falciparum (malaria) and
Cryptosporidium parvum was inhibited by the herbicide glyphosate, a well
characterized inhibitor of the shikimate pathway enzyme 5-enolpyruvyl shikimate 3
phosphate synthase. This effect on T. gondii and P. falciparum was reversed by
treatment with p-aminobenzoate, which suggests that the shikimate pathway
supplies folate precursors for their growth. Glyphosate in combination with
pyrimethamine limited T. gondii infection in mice. Four shikimate pathway enzymes
were detected in extracts of T. gondii and glyphosate inhibited 5-enolpyruvyl
shikimate 3-phosphate synthase activity. Genes encoding chorismate synthase, the
final shikimate pathway enzyme, were cloned from T. gondii and P. falciparum.
This discovery of a functional shikimate pathway in apicomplexan parasites
provides several targets for the development of new antiparasite agents.
PMID- 9655397
TI - Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase.
AB - Cell division, cell motility and the formation and maintenance of specialized
structures in differentiated cells depend directly on the regulated dynamics of
the actin cytoskeleton. To understand the mechanisms of these basic cellular
processes, the signalling pathways that link external signals to the regulation
of the actin cytoskeleton need to be characterized. Here we identify a pathway
for the regulation of cofilin, a ubiquitous actin-binding protein that is
essential for effective depolymerization of actin filaments. LIM-kinase 1, also
known as KIZ, is a protein kinase with two amino-terminal LIM motifs that induces
stabilization of F-actin structures in transfected cells. Dominant-negative LIM
kinasel inhibits the accumulation of the F-actin. Phosphorylation experiments in
vivo and in vitro provide evidence that cofilin is a physiological substrate of
LIM-kinase 1. Phosphorylation by LIM-kinase 1 inactivates cofilin, leading to
accumulation of actin filaments. Constitutively active Rac augmented cofilin
phosphorylation and LIM-kinase 1 autophosphorylation whereas phorbol ester
inhibited these processes. Our results define a mechanism for the regulation of
cofilin and hence of actin dynamics in vivo. By modulating the stability of actin
cytoskeletal structures, this pathway should play a central role in regulating
cell motility and morphogenesis.
PMID- 9655398
TI - Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin
reorganization.
AB - Rac is a small GTPase of the Rho family that mediates stimulus-induced actin
cytoskeletal reorganization to generate lamellipodia. Little is known about the
signalling pathways that link Rac activation to changes in actin filament
dynamics. Cofilin is known to be a potent regulator of actin filament dynamics,
and its ability to bind and depolymerize actin is abolished by phosphorylation of
serine residue at 3; however, the kinases responsible for this phosphorylation
have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a
serine/threonine kinase containing LIM and PDZ domains, phosphorylates cofilin at
Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1
induces actin reorganization and reverses cofilin-induced actin depolymerization.
Expression of an inactive form of LIMK-1 suppresses lamellipodium formation
induced by Rac or insulin. Furthermore, insulin and an active form of Rac
increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1
participates in Rac-mediated actin cytoskeletal reorganization, probably by
phosphorylating cofilin.
PMID- 9655399
TI - Structure of a heparin-linked biologically active dimer of fibroblast growth
factor.
AB - The fibroblast growth factors (FGFs) form a large family of structurally related,
multifunctional proteins that regulate various biological responses. They mediate
cellular functions by binding to transmembrane FGF receptors, which are protein
tyrosine kinases. FGF receptors are activated by oligomerization, and both this
activation and FGF-stimulated biological responses require heparin-like molecules
as well as FGF. Heparins are linear anionic polysaccharide chains; they are
typically heterogeneously sulphated on alternating L-iduronic and D-glucosamino
sugars, and are nearly ubiquitous in animal tissues as heparan sulphate
proteoglycans on cell surfaces and in the extracellular matrix. Although several
crystal structures have been described for FGF molecules in complexes with
heparin-like sugars, the nature of a biologically active complex has been unknown
until now. Here we describe the X-ray crystal structure, at 2.9 A resolution, of
a biologically active dimer of human acidic FGF in a complex with a fully
sulphated, homogeneous heparin decassacharide. The dimerization of heparin-linked
acidic FGF observed here is an elegant mechanism for the modulation of signalling
through combinatorial homodimerization and heterodimerization of the 12 known
members of the FGF family.
PMID- 9655400
TI - Endoscopic excision and repair of simulated bilateral cleft lips in fetal lambs.
AB - The use of nonpenetrating clips to accomplish wound closure as an alternative to
suture in the repair of simulated cleft lips in partially exteriorized fetuses
has been described previously. In this study, the fetus is approached
endoscopically, and clipped (n = 8) and sutured (n = 4) intrauterine endoscopic
repairs in six lambs (90- to 95-day gestation) are compared. Also used was a
newly developed harmonic scalpel to create the defects in the fluid environment.
Clipped repairs were nearly 10 times faster than sutured repairs (2.7 +/- 0.5
minutes compared with 24 +/- 4 minutes, respectively). Furthermore, suture
incited foreign body inflammation, recruited monocytic inflammatory cells, and
exhibited notable scarring. The comparison between clipped and sutured repairs
extends the previous observations to the realm of endoscopy and reinforces the
previous conclusions of this group that the nonpenetrating clip is more rapid and
incites less inflammation than suture in fetal wound approximation and repair.
PMID- 9655401
TI - Decreasing the perioperative complications associated with the superior
pharyngeal flap operation.
AB - This outcome study was a continuation of a previously published review. It
examined whether there had been a decrease in the number of acute perioperative
complications surrounding superior pharyngeal flap operations since a patient's
death in 1990. A total of 386 patients were divided into two groups: the early
group (July of 1985 to December of 1990) n = 164, and the later group (January of
1991 to June of 1996) n = 222, which were statistically comparable. The patient
complication rate decreased from 19.5 to 6.3 percent (chi square, p = 0.0001).
Airway obstruction decreased from 11 to 3.2 percent (chi square, p = 0.0012).
Bleeding complications decreased from 7.3 to 1.4 percent (chi square, p =
0.0027). The majority of airway complications (72 percent) and bleeding
complications (80 percent) occurred in the first 24 hours. Predictive factors for
complications included the surgeon involved, patients with associated medical
conditions, having an associated procedure performed concurrently, and leaving
the donor site open (multiple logistic regression). Hospital stay also decreased
from 5.8 +/- 2.5 to 3.8 +/- 1.6 days (Student's t test p = 0.0001). The decrease
in complication rate was due to the increased awareness of all staff involved and
also due to changes in surgical management, including a decrease in the number of
surgeons (from seven to four surgeons), a decrease in the number of associated
procedures (10.4 to 4.5 percent, chi square, p = 0.026), a decrease in the number
of open donor sites (34.8 to 4.5 percent, chi square, p = 0), and an increase in
the use of nasopharyngeal airways (17.1 to 45 percent, chi square, p = 0). The
superior pharyngeal flap operation has become a safer procedure in this hospital.
PMID- 9655402
TI - Periorbital melanocytic lesions: excision and reconstruction in 40 patients.
AB - The treatment of melanoma arising in the periorbital region is a difficult
reconstructive problem. The abundance of vital structures in close proximity to
one another makes the resection and subsequent reconstructive procedures
extremely challenging. Reported here is experience with periorbital melanocytic
lesions in 40 patients with the emphasis on the types of reconstruction
performed. Forty patients with periorbital melanocytic lesions were treated
between 1984 and 1995. The periorbital region was subdivided into five zones.
These zones are the following: zone I, upper eyelid; zone II, lower eyelid; zone
III, medial canthus; zone IV, lateral canthus; and zone V, contiguous structures.
Ocular melanomas were not included in this study. The distribution of the lesions
in our 40 patients was zone I (n = 1), zone II (n = 14), zone III (n = 1), zone
IV (n = 9), and zone V (n = 31). The ages of the patients ranged from 3 to 84
years at the time of reconstruction, with an average age of 57 years. Resection
and reconstruction were performed simultaneously in all patients. Thirty-six of
the patients were reconstructed with one procedure, three patients required two
procedures, and one patient required five procedures. The tumor type was
superficial spreading melanoma in 15 patients, melanoma in situ in 17 patients,
malignant spindle cell neoplasm in 2 patients, desmoplastic melanoma in 2
patients, amelanocytic melanoma in 1 patient, epithelioid melanoma in 1 patient,
and atypical melanocytic nevus in 2 patients in which an early, evolving melanoma
could not be excluded. Elective lymph node dissection was performed in four
patients for intermediate thickness lesions (1.5 to 4.0 mm). The types of
reconstructions performed included full-thickness skin grafts, upper lid
myocutaneous flaps, cheek advancement flaps, cervicofacial flaps, inferiorly
based nasolabial flaps, tarsoconjunctival flaps, frontalis muscle flaps, medial
transposition Z-plasty, and primary closure. The resection of periorbital
melanomas can be difficult because of the number of important anatomic structures
in the region. The challenge to the surgeon in handling head and neck melanomas
in general lies in the need to provide the best functional and aesthetic result
while still resecting the primary lesion with the intent of effecting a cure. We
present our series to demonstrate that the adequacy of margins of resection need
not be compromised to facilitate reconstruction and that excellent results are
obtainable with reconstructive procedures performed after adequate resections.
Several different types of flaps and grafts can be used, with the indications
varying depending on the location of the lesion and the extent of resection. The
major reconstructive options will be reviewed in detail.
PMID- 9655403
TI - Pediatric facial fractures: analysis of differences in subspecialty care.
AB - At the University of Michigan, the pediatric facial fracture call schedule
rotates through the plastic surgery, otolaryngology, and oral surgery services.
This situation provides an opportunity to evaluate differences in the management
of pediatric facial fractures between subspecialty groups. At this hospital, a
retrospective review of all pediatric facial fracture cases within a 5-year
period was undertaken. Sixty patients with 82 facial fractures were studied along
subspecialty lines. Differences in patient groups, practice patterns, and
treatment strategies based on subspecialty assignment were found. Overall
treatment followed traditional lines, with plastic surgeons involved in all types
of pediatric facial fractures, whereas otolaryngology and oral surgeons were more
limited in their operative scope, despite equal call responsibilities. It is
believed that the managed care arena is a competitive environment in which it
will be important to know the strengths and weaknesses of the plastic surgery
specialty, as well as those of competing specialties, as patient contracts are
negotiated. The overlap of plastic surgery, otolaryngology, and oral surgery in
the care of facial trauma could result in plastic surgeons being left off of
managed care participant lists. This study highlights plastic surgeons as
efficient deliverers of quality care for pediatric facial fractures. Although the
treatment of these fractures has fallen into the duties shared by all three
subspecialties, data such as those presented here should strengthen our ability
to succeed in the evolving environment of managed care.
PMID- 9655404
TI - Fever after craniofacial surgery in the infant under 24 months of age.
AB - A retrospective review was undertaken of 126 consecutive craniofacial procedures
involving a transcranial component, performed at the Children's Medical Center at
Dallas, between 1990 and 1994. Standard postoperative axillary temperature
measurements were recorded until discharge. Age at surgery of less than 24 months
correlated very strongly with a postoperative temperature of greater than 38
degrees C (r = -0.92). The incidence of postoperative fever was high in all age
groups, yet there was still a significant difference between the group younger
than 2 years and the group in which surgery was performed after the age of 2
years across all postoperative temperature ranges, from >38 degrees C to >39.5
degrees C (p < 0.001, chi-square test). The white blood cell count was elevated
above the age-related normal in 67 percent of febrile patients. There was no
correlation between type or duration of surgical procedure, length of intensive
care or hospital stay, or the need for blood transfusion and the development of a
significant postoperative fever. There were minor infectious complications in
four patients (3 percent), only one of which was a wound problem related to the
surgery. All infectious complications were easily identifiable clinically. There
was no mortality or serious infections. The development of postoperative fever,
and an elevated white blood cell count, is to be expected in pediatric patients
undergoing craniofacial procedures. The routine laboratory investigation of
postoperative fever in pediatric craniofacial patients under 2 years of age
without procedures involving transgression of the paranasal sinuses is not
warranted unless there are associated clinical indicators.
PMID- 9655405
TI - Comparative study of inferior alveolar disturbance restoration after sagittal
split osteotomy by means of bicortical versus monocortical osteosynthesis.
AB - The comparative study of neurosensory disturbance of the inferior alveolar nerve
after bilateral sagittal split osteotomies was carried out. The 112 patients who
underwent bilateral sagittal split osteotomies were divided into two groups: one
group consisted of 62 patients (124 osteotomy sites) who received bicortical
osteosynthesis using the lag screw principle (bicortical fixation group), and the
other group consisted of 52 patients (104 osteotomy sites) who underwent
monocortical osteosynthesis using miniplates (monocortical fixation group). The
incidence of neurosensory disturbance of the inferior alveolar nerve as well as
its recovery course was compared by patients' interview and Semmes-Weinstein
pressure esthesiometer. Mean follow-up period was 12 months (minimum 3 months,
maximum 36 months). The incidences of sensory disturbance of both groups were not
significantly different at 2 weeks postoperatively. During the period 6 to 12
months postoperatively, the number of patients having light touch sensory
disturbance was significantly less in the monocortical fixation group than in the
bicortical fixation group. Moreover, the number of patients complaining of
numbness during 6 to 18 months postoperatively was significantly less in the
monocortical fixation group. These findings suggested that the monocortical
osteosynthesis had less damage on the inferior alveolar nerve, leading to the
better restoration of neurosensory disturbance in patients in whom the nerve
damage was moderate.
PMID- 9655406
TI - Assessment of clinical outcome after flashlamp pumped pulsed dye laser treatment
of portwine stains: a comprehensive questionnaire.
AB - A generally accepted method to assess the clinical outcome of laser treatment of
portwine stains is not available. This paper describes the development and
evaluation of a comprehensive questionnaire for the assessment of the following
portwine stain characteristics: color (hue and lightness), sharpness of boundary,
pigmentation, size, shape, skin surface-structure, and hypertrophy of underlying
tissue. The questionnaire was applied to photographs of 70 patients with
previously untreated portwine stains in the head/neck area. Photographs were
taken before treatment and after five treatments of the entire portwine stain
with a flashlamp pumped pulsed dye laser. Each photograph was evaluated
separately by a panel of five professionals: the treating physician, two plastic
surgeons, a dermatologist, and a clinical photographer. Treatment results were
assessed by comparing ratings before and after treatment. Agreement among raters
was acceptable for all portwine stain characteristics, as was shown by weighted
kappa analysis. The reliability of the answers was further improved by taking the
average rating of the five panel members. The scores thus obtained were very
reliable, with Cronbach alpha coefficients of 0.8 on average. After five
treatments of the entire portwine stain, the most considerable changes were
measured in the ratings for color (lightening of the stain by 33 percent),
boundary (sharpness reduced by 38 percent), and size (13-percent decrease). Using
the questionnaire can be helpful in the design of comparative clinical trials on
portwine stain treatment and may facilitate comparison of treatment results
between different treatment centers and/or different lasers.
PMID- 9655407
TI - Skin-sparing mastectomy and immediate reconstruction: oncologic risks and
aesthetic results in patients with early-stage breast cancer.
AB - Skin-sparing mastectomy has been advocated as an oncologically safe approach for
the management of patients with early-stage breast cancer that minimizes
deformity and improves cosmesis through preservation of the skin envelope of the
breast. Because chest wall skin is the most frequent site of local failure after
mastectomy, concerns have been raised that inadequate skin excision could result
in an increased risk of local recurrence. Precise borders of the skin resection
have not been well established, and long-term local recurrence rates after skin
sparing mastectomy are not known. The purpose of this study was to evaluate the
oncologic safety and aesthetic results for skin-sparing mastectomy and immediate
breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast
prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal
carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy
and immediate reconstruction with a latissimus flap were studied from 1991
through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as
a 5-mm margin of skin designed around the border of the nipple-areolar complex.
After the mastectomy, biopsies were obtained from the remaining native skin flap
edges. Patients were followed for 44.8 months. Histologic examination of 114
native skin flap biopsy specimens failed to demonstrate breast ducts in the
dermis of any of the 32 consecutive patients studied. One of 26 patients with
ductal carcinoma in situ had metastases to the skin of the lateral chest wall and
back. Four other patients, one with stage I disease and three with stage II-B
disease, had recurrent breast carcinoma. The stage I patient had a local
recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients
suffered axillary relapse, and one had distant metastases to the spine. The
findings of this study support the technique of skin-sparing mastectomy as an
oncologically safe one, based on an absence of breast ductal epithelium at the
margins of the native skin flaps and a local recurrence rate of 2 percent after
45 months of follow-up. Although these results need to be confirmed with greater
numbers of patients and longer follow-up, skin-sparing mastectomy and immediate
breast reconstruction may be considered an excellent alternative treatment to
breast conservation for patients with ductal carcinoma in situ and early-stage
invasive breast cancer.
PMID- 9655408
TI - Aesthetic refinement in breast reconstruction: complete skin-sparing mastectomy
with autogenous tissue transfer.
AB - Aesthetic results in breast reconstruction are often compromised either by
prominent scars or by the presence of an island of skin that differs in color and
texture from the native breast skin. Complete skin-sparing mastectomy is a
technique by which breast scars can be largely eliminated and the need for a
visible skin island avoided. A circumareolar incision is used for mastectomy with
a separate axillary incision if needed. Autogenous tissue is used to fill the
skin envelope, and a disk of skin temporarily replaces the areola. Twenty-eight
patients treated by this method were reviewed retrospectively. Prerequisites
included a favorable biopsy scar location and a suitable tissue donor site. The
mean patient age was 42.5 years, and the majority were reconstructed with TRAM
flaps (92 percent). There was no evidence of increased morbidity or any instance
of local recurrence during a follow-up period, which averaged 25.7 months.
Aesthetic results were judged excellent in 12 patients, good in 11 patients, and
fair in 5 patients. Insufficient tissue volume, shape asymmetry, and areolar
position asymmetry were the most common factors that detracted from the quality
of the results. Advantages of this method, besides the prospect of an ideal
aesthetic result, include easier flap insetting and simplified subsequent
revision procedures. Disadvantages include the requirement of a skilled ablative
surgeon and incompatibility with conventional expander/implant methods of
reconstruction.
PMID- 9655409
TI - Efficient in vitro model for immunotoxicologic assessment of mammary silicone
implants.
AB - In clinical and experimental studies, silicone gel has been assumed to cause
immune alterations that may be related to macrophage activation of silicone
implants. However, it has not been proven that the immunotoxicities are caused by
the direct contact of macrophages and silicone gel because there has not been an
adequate experimental model. In the present study, silicone gel was loaded
directly onto Petri dishes and was distributed uniformly to the bottom by
centrifugation. Peritoneal macrophages and splenic lymphocytes were cultured
either on the silicone-coated plates or on the conventional, normal plates, and
their functions were compared with each other. The experiments were repeated
three times. The cytotoxic activities of peritoneal macrophages on cancer cells
were markedly augmented by cultivation on silicone gel, and the primary T
dependent immunoglobulin M response in which macrophages participated as antigen
presenting cells was also enhanced by incubation on silicone gel. However,
macrophage-unrelated functions mediated by B and T lymphocytes were not affected
by the silicone gel treatment. It was proven that the direct contact of
macrophages with silicone gel was a primary cause of acute immune activation that
was related to foreign body reaction. In addition, the present in vitro model
exhibited similar silicone-induced immunotoxicities in previous animal and
clinical studies.
PMID- 9655410
TI - The survival of human skin stored by refrigeration at 4 degrees C in McCoy's 5A
medium: does oxygenation of the medium improve storage time?
AB - To establish the viable storage time of human skin stored by refrigeration at 4
degrees C in McCoy's 5A medium and to establish whether oxygenating the medium
improves the viable storage time, the following experiment was conducted. Eighty
discs of human split-thickness skin graft, each 3 mm in diameter, were stored in
40 sterile sealable containers under four different conditions: in 0.9% saline,
in McCoy's 5A medium, in oxygenated McCoy's 5A medium, and in carbon dioxide
supplemented McCoy's 5A medium. Skin graft viability was assessed using tissue
culture. Skin stored in saline was viable for only 1 week, whereas skin stored in
McCoy's 5A medium and in oxygenated McCoy's 5A medium was viable for 4 weeks.
Skin stored in carbon dioxide supplemented McCoy's 5A solution did not even
survive the first week. These findings show that McCoy's 5A medium allows at
least 4 weeks of viable human skin storage by refrigeration at 4 degrees C.
Furthermore, oxygenating the medium does not seem to improve the viable storage
time, and carbon dioxide supplementation is detrimental. The advantages of skin
storage by refrigeration and the implications of the above findings are
discussed. A clinical case in which split-thickness skin was stored for
approximately 5 weeks and still resulted in good graft take is quoted as an
example of our experience with the use of McCoy's 5A medium.
PMID- 9655411
TI - Electrically stimulated free-flap graciloplasty for urinary sphincter
reconstruction: a new surgical procedure.
AB - In electrically stimulated (dynamic) graciloplasty for urinary incontinence, the
gracilis muscle is transposed into the pelvis, and the distal part is used to
reconstruct a neosphincter. Clinical outcomes using this technique have been
disappointing due to stricture of the urethra caused by ischemia in the distal
part of the gracilis and limited gracilis length available for neosphincter
construction. Furthermore, the urethra is twisted by the contracting gracilis,
rather than circumferentially squeezed. The purpose of the present study was to
test the anatomical and functional feasibility of a new surgical approach to
reconstruct a urinary sphincter, using the gracilis muscle as a free flap. In 12
human cadavers, the anatomical feasibility for creating a neosphincter by using
the gracilis free flap was determined. In all cases, transfer of the gracilis
muscle into the pelvis as a free flap (with the nerve intact) was feasible, and
ample muscle was available to construct a neosphincter around the bladder neck.
Gracilis neosphincter function was studied in seven dogs. The left gracilis
muscle was subjected to transfer into the pelvis as an innervated free flap to
create a neosphincter around the urethra. The right (control) gracilis muscle was
lifted as a single pedicle flap, remained in situ, and was wrapped around a stent
to mimic the urethra. Function (expressed as peak pressure generation and fatigue
rate) and surface perfusion were determined for all gracilis muscles. In each
dog, both sides were compared using the paired Student's t test for statistical
analysis, and no significant difference was measured for the two groups. In
conclusion, an innervated gracilis free flap can be used to create a neosphincter
around the bladder neck. In an acute study in dogs, function and perfusion of the
innervated gracilis free flap are not compromised.
PMID- 9655412
TI - Distraction osteogenesis in the hand.
AB - Distraction osteogenesis was used to correct congenital hand deformities in 12
digits. The patients' ages at the time of distraction ranged between 2.5 and 7
years. A total of nine patients underwent lengthening of 12 bones. The average
period of distraction was 31.1 +/- 17.6 days. The average length of distraction
was 23.6 +/- 7.3 mm. Seventeen percent of the patients after lengthening had an
angular deformity that required remodeling of the regenerate. No infections were
noted. Distraction osteogenesis provides a useful tool for reliable and
predictable correction of osseous defects with vascular bone in patients with
congenital anomalies of the hand.
PMID- 9655413
TI - "Spaghetti wrist": management and results.
AB - A retrospective review of 60 patients with "spaghetti wrist" lacerations operated
on by the authors between July of 1988 and June of 1996 was completed. Spaghetti
wrist injuries were defined as those occurring between the distal wrist crease
and the flexor musculotendinous junctions involving at least three completely
transected structures, including at least one nerve and often a vessel. A total
of 41 men and 19 women, average age of 29.0 years (range, 5 to 54 years),
sustained spaghetti wrist injuries. The most frequent mechanisms of injury were
accidental glass lacerations (61.0 percent), knife wounds (23.7 percent), and
suicide attempts (8.5 percent). An average of 7.8 structures were injured
including 5.8 tendons, 1.2 nerves, and 0.73 arteries. The most frequently injured
structures were flexor carpi ulnaris (66.7 percent), median nerve (60.0 percent),
flexor digitorum superficialis 2-5 (59.2 percent), ulnar nerve (58.3 percent),
and ulnar artery (56.7 percent). A predilection for injury to the ulnar
structures was observed. The flexor carpi ulnaris was more commonly injured than
the more superficial central and radial palmaris longus (48.3 percent) and flexor
carpi radialis (45.0 percent). The most common pattern of injury involved the
ulnar nerve and artery and flexor carpi ulnaris, or so-called ulnar triad (41.7
percent). Combined median nerve, flexor carpi radialis, and palmaris longus
lacerations occurred in 26.7 percent. Simultaneous lacerations of both median and
ulnar nerves occurred in 23.3 percent. No distinct pattern of injury was noted in
patients with simultaneous injury to both nerves. Simultaneous lacerations of
both ulnar and radial arteries occurred in 6.7 percent; neither artery was
injured in 33.3 percent. In the subset of 19 patients available for follow-up
examination, range of motion was excellent in 12 patients and good in 7 patients.
In 12 patients with sufficient follow-up, intrinsic muscle recovery was good in 7
patients and fair to poor in 5 patients. Sensory return was disappointing: seven
patients recovered only protective sensation and five patients demonstrated
return of two-point discrimination that ranged from 7 to 12 mm in three patients
and from 2 to 6 mm in two patients.
PMID- 9655414
TI - Extensor digitorum brevis muscle flap: new refinements.
AB - Two original operative techniques of raising the extensor digitorum brevis muscle
flap are presented. These methods allow for covering distal foot defects that are
difficult to cover by other reconstructive means. In the first technique, the
flap is based on an extended distal pedicle supplied by the dorsal interosseous
artery of the first intermetatarsal space. In the second technique, the flap
receives its vascular supply from the medial tarsal artery; this procedure may be
valuable when the vascular supply of the dorsalis pedis pedicle has been
disrupted. To confirm the availability of these vascular pedicles, cadaver
dissections were performed and proved that the extended pedicle dissection
enhances the rotation arc of the flap. Four selective clinical cases, in which
the flap was successfully used, are discussed. Advantages of these techniques, in
reconstructing large defects in the distal foot, are delineated.
PMID- 9655415
TI - Limb-salvage in reconstruction of recalcitrant pressure sores using the
inferiorly based rectus abdominis myocutaneous flap.
AB - Pressure sore closure is frequently a reconstructive challenge. This challenge is
particularly evident in cases of multiply recurrent sores. In such settings,
there are often opportunities to manage the recurrent wounds either by repeated
advancement of previous flaps or by design of alternative ones. However, these
interventions are not always feasible, and limb amputation with total thigh flap
closure must be considered. A review of operative experience with seven such
complex pressure sores in seven patients is presented. Each patient had
previously suffered a permanent thoracic-level spinal cord injury. Prior attempts
at wound closure were unsuccessful. Despite consideration of all described
locoregional flaps, no limb-sparing procedure could be designed satisfactorily.
As an alternative to either hip disarticulation and total thigh flap coverage or
distant free-tissue transfer, we reconstructed the debrided ulcer beds with
inferiorly based rectus abdominis myocutaneous flaps. Six of the seven wounds
healed primarily, whereas one required repeated debridement and the addition of a
gracilis muscle flap to achieve complete closure. Postoperative follow-up has
ranged from 6 to 45 months. Each patient has returned to his baseline
preoperative activity level with no clinical compromise of abdominal wall
function. All wounds have healed. Successful application of the inferiorly based
vertical rectus abdominis myocutaneous flap for cases of both recalcitrant
ischial and trochanteric pressure sores is demonstrated and its consideration is
advocated if no reconstructive options short of extremity amputation and total
thigh flap coverage exist for such challenging sores.
PMID- 9655416
TI - Determination of endogenous growth factors in human wound fluid: temporal
presence and profiles of secretion.
AB - Growth factors are important substances in the central control of wound healing
during the exudative phase. Although these peptides have been applied frequently
to chronic wounds in clinical studies, little is known about the naturally
occurring levels at the wound site in correlation to healing in superficial
wounds. We have therefore investigated the presence of these cytokines in partial
thickness wounds. In 16 patients undergoing reconstructive surgery, split
thickness skin wounds were enclosed in cutaneous vinyl chambers filled with 2.5
ml of saline. Chambers placed over unwounded skin served as controls. After 24
hours, the accumulated wound fluid was harvested and replaced by 2.5 ml of saline
until the wounds were healed. Wound fluid was centrifuged, aliquoted, and frozen
at -70 degrees C. Samples were analyzed for protein and growth factors (insulin
like growth factor-1, epidermal growth factor, basic fibroblast growth factor,
platelet-derived growth factor-AB, interleukin-1alpha, and transforming growth
factor-beta1 and -beta2) and insulin-like growth factor-binding proteins 1 and 3
using a monoclonal Sandwich enzyme-linked immunosorbent assay and
radioimmunoassay. All wounds healed in the liquid environment within 7 days
(macroscopically) and 11 days (barrier function), respectively. In wound fluid,
protein concentrations dropped from 5 mg/ml on day 1 to a baseline of 0.1 mg
(unwounded skin), indicating a return of the barrier function. All growth factors
could be measured already after 24 hours postwounding. However, the
concentrations measured varied from 10 to more than 10,000 pg/ml between the
different factors. The highest range was found for insulin-like growth factor-1
(21,000 to 41,000 pg/ml), the lowest for epidermal growth factor (3 to 63 and 3
to 88 pg/ml, respectively). Two different patterns of kinetics were
distinguished: (1) a high initial peak decreasing to baseline values or below
serum levels by the time of healing (insulin-like growth factor-1, insulin-like
growth factor binding protein-1, -3, basic fibroblast growth factor, epidermal
growth factor, platelet-derived growth factor-AB, transforming growth factor
beta1) and (2) a low initial concentration followed by an increase to a maximum
at the time of epithelialization (interleukin-1alpha, transforming growth factor
beta2). Comparing the growth factor levels measured to serum baseline values, it
was found that four of the growth factors appeared in wound fluid at above serum
concentrations (interleukin-1alpha, transforming growth factor-beta2, basic
fibroblast growth factor, epidermal growth factor); the other factors never
reached serum values in wound fluid (insulin-like growth factor, transforming
growth factor-beta1, platelet-derived growth factor-AB). It is concluded that the
different profiles of secretion might reflect different functions of polypeptide
growth factors such as stimulation of epithelialization (epidermal growth factor,
insulin-like growth factor-1), matrix synthesis (transforming growth factor
beta), and inflammatory stimulation (interleukin-1alpha). The concentrations
determined could serve as guidelines for adapted administration of growth factors
once correlations to healing disorders such as overhealing and ulceration are
established.
PMID- 9655417
TI - Human wound contraction: collagen organization, fibroblasts, and myofibroblasts.
AB - The closure of ungrafted sacrococcygeal pilonidal sinus excisional wounds was
studied in 15 patients. Wound punch biopsies were taken on a regular basis, and
histologic sections were made. To document changes, computer-assisted
morphometric image analysis was employed. Initial average wound depth was 37.8 +/
4.6 mm, and complete closure (0 wound depth) was reached by 68 days. Wound
contraction contributed 88 percent to wound closure, whereas the deposition of
scar only contributed 12 percent. Maximum cells density within granulation tissue
was reached by day 18. Myofibroblasts, identified by alpha-smooth muscle actin
immunostaining, first appeared on day 11. Unlike those observed in laboratory
animals, myofibroblasts were a minor cell population of granulation tissue, never
exceeding 10 percent of the cells. The pattern of collagen fiber organization was
documented by polarized light microscopy of Sirius red-stained sections. Early
granulation tissue collagen fibers demonstrated a fine greenish birefringence,
whereas more mature granulation tissue collagen fibers were thicker, displaying
orange-yellowish birefringence. Myofibroblasts were associated exclusively with
thicker collagen fibers, whereas fibroblasts were associated with both fine and
thick collagen fibers. It is proposed that human wound contraction involves a
volume change whereby normal dermal and adipose tissues are pulled into the
defect by forces generated within fibroblasts.
PMID- 9655418
TI - Epidermal regulation of dermal fibroblast activity.
AB - Although the association between delayed burn wound healing and subsequent
hypertrophic scar formation is well-established, the mechanism for this
relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a
possible regulatory role for the epidermis in controlling dermal fibroblast
matrix synthesis. Therefore, we examined the effect of epidermal cells and media
conditioned by epidermal cells on fibroblast collagen synthesis and replication.
Purified fibroblast and keratinocyte cell strains were developed from discarded
normal adult human skin. Conditioned media were created by incubation of cytokine
free and serum-free medium with either confluent fibroblast or keratinocyte
cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed
for 48 hours to graded concentrations of either unconditioned medium (control),
conditioned medium, or varying numbers of keratinocytes. Replication was
quantified by the incorporation of 3H-thymidine. Collagen synthesis was measured
by the incorporation of 3H-proline into collagenase-sensitive protein. Data were
compared using analysis of variance (ANOVA) and linear regression. Keratinocyte
conditioned medium induced a significant increase in replication (n = 3) (p =
0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast,
neither fibroblast conditioned medium nor control medium had an effect on
fibroblast replication or collagen synthesis. Co-culture of fibroblast with a
graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p
< 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a
soluble keratinocyte product. This result suggests a mechanism for the clinical
observation that unhealed burn wounds, which lack the epidermis, demonstrate
excess collagen production and scar. Clinical strategies to decrease hypertrophic
scar should include an attempt at early wound closure with skin grafting or the
application of cultured epithelial autografts.
PMID- 9655419
TI - Ischemic preconditioning improves the survival of skin and myocutaneous flaps in
a rat model.
AB - Inadequate blood supply of pedicle flaps results in partial necrosis, and
prolonged ischemia during free-tissue transfer can result in partial or complete
flap necrosis. Recent research in the field of cardiovascular surgery has shown
that ischemic preconditioning (repeated brief episodes of coronary artery
occlusion followed by reperfusion) improves myocardial muscle survival when the
heart is subsequently subjected to prolonged ischemia. Preconditioning of skin or
myocutaneous flaps as either pedicle or free flap models has never been studied.
The goal of this investigation was to measure the effect of ischemic
preconditioning on myocutaneous and skin flap survival areas and total necrosis
rates after variable periods of global ischemia. In 220 rats, 100 transverse
rectus abdominis myocutaneous flaps and 120 dorsal cutaneous flaps were
randomized into treatment and control groups. The treatment flaps underwent
preconditioning by three cycles of 10 minutes of pedicle clamping followed by 10
minutes of reperfusion for a total preconditioning period of 1 hour. The control
flaps were perfused without clamping for 1 hour. Both control and treatment flaps
then underwent global ischemia for 0, 2, 4, 6, 10, or 14 hours by pedicle
clamping. Flap survival area was measured on the fifth postoperative day.
Statistical analysis was performed with analysis of variance, student's t tests,
and probit analysis. Preconditioning improved survival areas of pedicle
myocutaneous flaps (0-hour group) from 47 +/- 16 percent (mean percent area
surviving +/- SD) to 63 +/- 5 percent. This difference was statistically
significant (t test, p < 0.04). There was no statistically significant
improvement in pedicle skin flap survival. For free flap models (flaps undergoing
global ischemia), preconditioning increased the survival areas of skin and
myocutaneous flaps (analysis of variance, p < 10(-5)). For the skin flap model,
statistical significance of the survival area difference was reached at 6, 10,
and 14 hours of ischemia (t test, p < 10(-4)). The magnitude of this effect was
higher in the myocutaneous flap model and reached statistical significance at 2,
4, 6, and 10 hours of ischemia (p < 10(-3)). Preconditioned flap survival areas
were increased by two to five times that of non-preconditioned flaps at these
ischemia times. Preconditioning lowered total necrosis rates at all ischemia
times for both flap models. The critical ischemia time when 50 percent of skin
flaps became totally necrotic (CIT50) improved from 6.9 to 12.4 hours by
preconditioning. Similarly, preconditioning improved the CIT50 of myocutaneous
flaps from 3.6 to 9.2 hours. For the first time, statistically significant
improvements of partial necrosis areas and total necrosis rates have been
demonstrated through intraoperative ischemic preconditioning of skin and
myocutaneous flaps. In clinical practice, application of this technique may lead
to improved survival during pedicled or free transfer of myocutaneous flaps and
free transfer of skin flaps.
PMID- 9655420
TI - Involvement of neutrophils in ischemia-reperfusion injury of inguinal island skin
flaps in rats.
AB - Increased production of oxygen free radicals and infiltration of neutrophils into
tissue subjected to ischemia-reperfusion have emphasized that neutrophils play a
direct role in the development of injury. The present study was designed to
elucidate the effect of FK506, a new immunosuppressive drug, on 11 hours of
complete ischemia and reperfusion of the inguinal island skin flaps in rats.
Group 1 (n = 10) control animals underwent ischemia and reperfusion and no
treatment. Group 2 (n = 10) animals received FK 506 0.3 mg/kg/day, and group 3 (n
= 9) animals received 0.5 mg/kg/day intramuscularly for 3 days before the
ischemia. The effect of the drug was evaluated by measuring flap survival and
tissue malondialdehyde content and myeloperoxidase activity and also by
histopathologic examination of the skin specimens taken at the 1st and 24th hour
after reperfusion. The survival of flaps controlled for 7 days was found to be
significantly improved in group 2 (65.0 +/- 10.93 percent) and group 3 (93 +/-
6.25 percent) when compared with the control group (14 +/- 10.12 percent) (p <
0.04 and p < 0.0001). The tissue contents of malondialdehyde and activities of
myeloperoxidase were significantly lower in groups 2 and 3 than in the control
group. Three days of pretreatment with FK506 significantly reduced neutrophil
infiltration in groups treated with either of the doses. These results showed
that neutrophils play an important role in island flap survival associated with
ischemia-reperfusion injury. Increased neutrophil infiltration was found related
with increased levels of malondialdehyde and myeloperoxidase. Flap necrosis and
the increase in malondialdehyde, myeloperoxidase, and neutrophil infiltration
were improved by FK506 pretreatment, a neutrophil modulating agent.
PMID- 9655421
TI - Cell transplantation from limb allografts.
AB - A murine model of skeletal tissue transplantation was developed to study the
allograft rejection process in mice for limb allograft transplantation. Muscle,
bone, and skin have been shown to be strong antigenic stimuli in vascularized
allograft models, and cells from these sources were used for transplantation.
Using enzymatic digestion, keratinocytes, myocytes, and osteocytes were harvested
from B10.A mice tissues, dissociated into single cells, and then grown in culture
for 14 to 21 days. Each cell type was marked with an intracellular fluorescent
marker before transplantation of the cells into pockets in the rectus abdominis
muscle of a syngenic host. All cell types remained viable and were detectable 2
weeks following transplantation when examined histologically and observed under a
fluorescent microscope. Transplanted osteocytes were found to produce bone 8
weeks following transplantation. These results demonstrate that individual cells
transplanted into muscle pockets survive and have the ability to produce
extracellular matrix in this mouse model of skeletal tissue transplantation. Use
of this model will allow transplantation of the cellular components comprising
limb allografts to study the relative antigenicities and the rejection of the
separate cells with the advanced immunologic techniques available for mice. A
better understanding of immunologic responses to these individual tissue
components may enable specific donor tissue or host immune modification to
achieve skeletal tissue transplantation without immunosuppression. These findings
are particularly valuable to the field of tissue engineering where allogeneic
cells may be used in cell/polymer constructs for reconstructive procedures.
PMID- 9655422
TI - Replantation of amputated nose by microvascular anastomosis.
PMID- 9655423
TI - Modified chondrocutaneous advancement flap for ear reconstruction.
PMID- 9655424
TI - Endoscopically assisted suspension in facial palsy.
PMID- 9655425
TI - Conversion from tridimensional surface to a plane for measuring expanded skin
area with computer aid.
PMID- 9655426
TI - The pedicled tensor fasciae latae flap as a salvage procedure for an infected
abdominal mesh.
PMID- 9655427
TI - Simultaneous rhytidoplasty and lipoinjection: a comprehensive aesthetic surgical
strategy.
AB - Fat autografting is an accepted technique in the treatment of depressions or
augmenting thin soft tissues. Aging soft tissues become thin, among them the
subcutaneous fat layer, muscles, and fasciae, and these tissues in addition
become flaccid. Therefore, to get better results in rejuvenation plastic surgery,
a good alternative is the combination of lifting the flaccid tissues and
thickening the thin soft tissues with a lack of contour and definition, which
enhances the aspect of the entire face and neck. For 10 years in our practice, we
have been combining rhytidoplasty (which includes systematizing superficial
musculoaponeurotic system and platysma plication) with lipoinjection, placing
thin rolls of autologous fat into the facial and cervical muscles, or at least
under the fasciae. The results reveal a very high success rate with few minor
complications. Proper diagnosis, patient selection, and adequate surgical
technique produce predictable and favorable aesthetic results. A concurrent
retrospective study of 357 consecutive patients who underwent simultaneous
rhytidoplasty and lipoinjection was conducted over a 10-year period (1985 to
1995). The purpose of this article is to show our experience with this method,
including long follow-up observations.
PMID- 9655428
TI - Numerical modeling of facial aging.
AB - Facial aging is a biological phenomenon. Skin properties change with time, and
gravity and facial expressions exert mechanical deformation. Knowledge of these
alterations may suggest ways to reverse them by identifying the corresponding
distortional forces. The aim of this study was to determine a pattern of change
for parameters of the face during the aging process, based on the numerical
fitting of measures from a sample of patients. The first aspect of this study was
to define adequate facial parameters and means of measuring them. Subsequently,
each parameter was defined individually, and these data were analyzed as a set.
The sample for the research was restricted to a group of 40 white female patients
with a history of limited exposure to the sun, with ages ranging from 25 to 65.
The reason for choosing this sample was the availability of frontal pattern
photographs at different ages. The parameters for each patient were measured at
two different ages. A strong correlation was found between age and behavior of
the parameters. This aging model can be verified qualitatively by comparing
photographs of a patient with manipulated photographs simulating aging. The
quantitative verification of the model was done through the comparison of the
measured and the predicted parameters.
PMID- 9655429
TI - Relative maxillary retrusion as a natural consequence of aging: combining
skeletal and soft-tissue changes into an integrated model of midfacial aging.
AB - The contribution of maxillary retrusion to the formation of the nasolabial fold
is evaluated in the present study. Clinical observation of patients from the
craniofacial unit with concomitant maxillary retrusion revealed prominent signs
of midfacial aging: specifically these individuals displayed a prominent
nasolabial fold at an early age. This observation led to the hypothesis that
relative maxillary retrusion occurs as a normal feature of the aging process.
Retrusion of the lower facial skeleton below the soft tissue of the nasolabial
fold causes the nasolabial fold to appear more prominent. To test this
hypothesis, computed tomographic data were assembled retrospectively and included
both males and females, young and old. The age range of the males (n = 14) was 18
to 24 years (young) and 43 to 57 years (old); the age range of the females (n =
14) was 15 to 30 years (young) and 43 to 57 years (old). All individuals had
complete upper dentition and had no bony facial injury. Computed tomographic data
were reconstructed into three-dimensional images, and a technique was developed
to create a standardized lateral view which eliminated rotational variance.
Analysis of anterior-posterior changes showed that there is a tendency for the
lower maxillary skeleton at pyriform to become retrusive with age relative to the
upper face in individuals with complete dentition. Findings were very significant
for both males and females (p = 0.0001 and p = 0.002, respectively). In both
groups, a slight increase in vertical maxillary dimension was noted, consistent
with previous studies. It is suggested that relative maxillary retrusion is a
factor in the development of the nasolabial fold. The skeletal features of normal
midfacial aging can be combined with the soft-tissue features such as ptosis and
atrophy into an integrated model of midfacial aging. A model such as this has
significance regarding both the timing and choice of procedure used to restore
the aging midface.
PMID- 9655430
TI - The tissue effects of ultrasound-assisted lipoplasty.
AB - The objective of our study was to investigate the effects of ultrasonic energy on
tissues, using a porcine model, performed under various instrumental and
procedural parameters. Domestic pigs were anesthetized and prepared for surgery.
An incision was made on the side of the hip randomly assigned to the right or
left side. Tumescence solution was infiltrated via a blunt tip, small diameter
cannula, followed by performance of standard liposuction. On the contralateral
side, a similar incision was made. For ultrasonic liposuction experiments without
the sheath, a percutaneous introducer was inserted into the incision, which was
protected at the entry site from contact with the cannula. Tumescence solution
was infiltrated via a blunt tip, small diameter cannula, and then the site was
treated with ultrasonic energy at maximum output from the machine with
liposuction concurrent through the hollow cannula. The experiments with the
sheath did not require a pretreatment with tumescence solution but consisted of
tumescence solution pumped through the sheath at a low infusion rate, with
concurrent treatment utilizing ultrasonically assisted liposuction through the
central lumen of the cannula. In all cases, the lipoaspirate was preserved for
biochemical analysis. After treatment, the pigs were euthanized, and samples for
histopathology were taken. The pigs were then perfused with a radio-opaque
solution through the left ventricle following preperfusion with saline. The
groups were ultrasound-assisted liposuction with sheath (n = 3), ultrasound
assisted without sheath (n = 4), and tumescence alone (n = 1), with standard
liposuction performed on the contralateral side for all ultrasound-assisted
liposuction animals. The lipoaspirates from the ultrasonically assisted
liposuction with the sheath showed significantly less blood loss (measured as
hemoglobin in the aspirate) than standard liposuction (p = 0.012) at comparable
levels of fat (measured as triglycerides in the aspirate). The lipoaspirates from
ultrasound-assisted liposuction without the sheath showed blood loss comparable
to that experienced with standard liposuction. The ratio of hemoglobin to
triglyceride was lowest in the ultrasound-assisted group with (p = 0.01) and
without (p = 0.06) the sheath when compared to traditional liposuction. In both
of these treated groups, the radiograms of the perfused areas showed
significantly less vascular disruption when compared with suction-assisted
liposuction. Histopathologic examination of specimens taken from various treated
areas showed substantial tissue damage comparable in ultrasound- and suction
assisted liposuction treated groups. This preliminary experimental study showed
that ultrasound-assisted lipoplasty is comparable to traditional suction-assisted
lipoplasty. Treatment with ultrasound provided more significant
hemoglobin/triglyceride ratios, indicative of more lipid aspirated per hemoglobin
lost, and better preservation of vascular tissues as demonstrated by our
perfusion studies. Treatment with the sheath showed a significantly lower
hemoglobin release with a diminished volume infused into the subcutaneous space
during the procedure.
PMID- 9655431
TI - Follicular bisection in hair transplantation surgery: an in vitro model.
AB - The aim of this study was to evaluate, in an in vitro model, the survival and
growth rates of transversely sectioned human hair follicles to assess
experimentally the soundness of this approach as a future possible method for
"duplicating" available donor hair grafts in hair transplantation procedures. A
total of 300 human anagen hair follicles was obtained from 10 healthy male
patients. Follicles were thus randomly assigned to one of the following groups:
group A (control; n = 100 follicles), cultured intact as dissected, and group B
(experimental; n = 200 follicles), transversely transected, parallel to the
epidermal surface and immediately below the bulge area, to obtain 200 lower-half
follicles and 200 upper-half follicles. Isolated hair follicles from both groups
were maintained in culture for 10 days. The length of each follicle was measured
immediately following isolation and at the end of the 10-day culture period. No
statistically significant differences were found between the growth rate of
intact follicles (mean 10-day growth rate = 2.71 mm) and of lower-half follicles
(mean 10-day growth-rate = 2.64 mm), whereas a statistically significant
difference was found between the growth rate of follicles from the two above
mentioned groups and the growth rate of the "upper-half" follicles (mean 10-day
growth rate = 1.07 mm). Histologic analysis demonstrated that both intact and
lower-half follicles maintained a normal histologic appearance, whereas in upper
half follicle sections we invariably detected a region of intense cell
proliferation, reminiscent of a regenerated follicular papilla, surrounding the
lowermost part of the follicle. In our opinion, the reported in vitro survival
rate of transected human hair follicles might represent an interesting starting
point in striving to augment the number of donor hairs available during a hair
transplantation procedure.
PMID- 9655432
TI - Late infection of a breast prosthesis with Enterococcus avium.
PMID- 9655433
TI - Umbilicated nipples eversion after breast augmentation.
PMID- 9655434
TI - Acute median nerve compression associated with tumescent fluid administration.
PMID- 9655435
TI - Calvarial fixation during endoscopic brow lift.
PMID- 9655436
TI - Resorbable screw fixation technique for endoscopic brow and midfacial lifts.
PMID- 9655437
TI - Simple technique to correct the bony septum.
PMID- 9655438
TI - Breast reduction ad absurdum.
PMID- 9655439
TI - Molecular basis for tissue expansion: clinical implications for the surgeon.
AB - A wide variety of tissue expansion techniques have been used for breast
reconstruction, craniofacial surgery, and burn care in plastic reconstructive
surgery. However, the basic mechanism by which skin and surrounding tissue
respond to mechanical expansion remains unclear. Recent studies have revealed the
biomechanical aspects of cells subjected to strain and various factors involved
in the stretch-induced signal transduction pathway. In this regard, we have
reported previously that mechanical force increases keratinocyte growth and
protein synthesis and alters cell morphology. The mechanism by which strain
causes an enhancement of cellular growth appears to be a network of several
integrated cascades, implicating growth factors, cytoskeleton, and the protein
kinase family. Recently, additional evidence has accumulated that mechanical
strain stimulates signal transduction pathways that could trigger a series of
cascades eventually leading to a new skin production. For example, we have
evidence suggesting a key role for protein kinase C (PKC) in mechanosignaling as
PKC is activated and translocated in keratinocytes subjected to strain in an
isoform-specific manner. In this report, molecular mechanisms leading to
enhancement of skin surface area are reviewed, and possible future applications
are discussed.
PMID- 9655440
TI - Maxillomandibular fixation utilizing cortical bone screws.
PMID- 9655441
TI - The box frame fixator: a technique for simultaneous fracture and free-tissue
transfer management.
PMID- 9655442
TI - Arteriovenous shunts.
PMID- 9655443
TI - Primary repair of whole-shaft epispadias with cleft glans penis in a 30-year-old
man.
PMID- 9655444
TI - Should electrodiagnostic studies be done in patients with carpal tunnel syndrome?
PMID- 9655445
TI - Surgical treatment of abdominal pain after mammary reconstruction by pedicled
transverse rectus abdominis muscle (TRAM) flap.
PMID- 9655446
TI - The best of Goldwyn collection.
PMID- 9655447
TI - Venous drainage of the reverse-flow flap.
PMID- 9655448
TI - Lessening the pain of suture removal.
PMID- 9655449
TI - Alternative wound dressings.
PMID- 9655450
TI - The Baker phenol peel formula.
PMID- 9655451
TI - Early orthodontic therapy of cleft lip and/or palate patients.
PMID- 9655452
TI - A new approach for the treatment of recurrent large abdominal hernias: the
overlap approach.
PMID- 9655453
TI - Use of polyfilament suture as a source of microsuture.
PMID- 9655454
TI - Bleeding of silicone gel breast implants.
PMID- 9655455
TI - Muscle flap ischemia secondary to acute arterial desaturation following
extubation.
PMID- 9655456
TI - Safety and efficacy report: external fatty tissue massage.
PMID- 9655457
TI - Reconstruction of a large thoracoabdominal wall defect.
PMID- 9655458
TI - Nevoid hyperkeratosis of the areola.
PMID- 9655459
TI - Mammography of the postreconstruction breast.
PMID- 9655460
TI - Postphlebitic ulcer treated by means of neurocutaneous distally based sural flap.
PMID- 9655461
TI - The posterior interosseous cutaneous flap.
PMID- 9655462
TI - Prenatal counseling for cleft lip and palate.
PMID- 9655463
TI - Triangular flap for a red lip: a simple modification for cleft lip surgery.
PMID- 9655464
TI - How are we to judge?
PMID- 9655465
TI - Long-term possible hazardous effects of ultrasonically assisted lipoplasty.
PMID- 9655466
TI - Ultrasonic surgical aspiration: instrumentation, clinical experience, and safety.
PMID- 9655467
TI - Chemokine receptor expression in cultured glia and rat experimental allergic
encephalomyelitis.
AB - Chemokines are a group of pro-inflammatory peptides that mediate leukocyte
migration and activation. Several members of the chemokine family have been shown
to be synthesized by cells of the central nervous system (CNS). To begin to
address the role of chemokine receptors in CNS physiology, we identified, by
molecular cloning techniques, the rat orthologs of the chemokine receptors, CCR2,
CCR3, CCR5, and CXCR4. CCR2 and CCR5 expression was detected in rat spleen, lung,
kidney, thymus and macrophages; CCR5 mRNA was also detected in rat brain. Primary
cultures of rat microglia expressed CCR5 mRNA that was regulated by IFN-gamma,
while both cultured astrocytes and microglia were found to contain mRNA for CXCR4
and CX3CR1. Induction of experimental allergic encephalomyelitis (EAE) in the rat
was accompanied by increased levels of CCR2, CCR5, CXCR4, and CX3CR1 mRNAs in the
lumbar spinal cords of animals displaying clinical signs of the disease. These
data identify the rat orthologs of chemokine receptors and demonstrate that
brain, spinal cord, and cultured glial cells express chemokine receptors that can
be regulated both in vitro and in vivo.
PMID- 9655468
TI - Linkage and association analysis of genes encoding cytokines and myelin proteins
in multiple sclerosis.
AB - Several genetic factors are likely to play a role in the etiology of multiple
sclerosis (MS). We used a candidate gene strategy in a study of polymorphic
markers within or close to genes encoding cytokines (interferon-gamma (IFN
gamma), interleukin-2 (IL-2), IL-4, IL-4 receptor (IL-4R), IL-10, transforming
growth factor-beta1 and -beta2) and myelin proteins (2',3'-cyclic-nucleotide 3'
phosphohydrolase (CNP:ase), myelin associated glycoprotein, oligodendrocyte
myelin glycoprotein, proteolipid protein) in 34 Swedish multiplex MS families and
in 147 sporadic MS patients and 95 healthy controls. No evidence for linkage was
observed in two-point linkage analysis. However, a slightly positive LOD score of
0.88 (theta = 0.01) for IFN-gamma was found. Affected pedigree member (APM)
analysis indicated a possible linkage with TGF-beta2 (p = 0.008) and IL-4R (p =
0.043). None of the cytokine markers were associated with MS in case-control
analysis. Our results suggest a possible importance of the TGF-beta2, IL-4R and
IFN-gamma genes in MS.
PMID- 9655469
TI - MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an
immunohistochemical and in situ hybridization study.
AB - Chemokines are low molecular weight chemotactic cytokines that have been shown to
play a central role in the perivascular transmigration and accumulation of
specific subsets of leukocytes at sites of tissue damage. Two major families have
been defined depending on the positioning of four conserved cysteines. The CXC
chemokines predominantly attract neutrophils, whereas the CC chemokines
predominantly attract monocytes and other leukocyte cell types. Members of the
monocyte chemotactic protein (MCP)-1 family form a major component of the CC
family of chemokines and are considered the principal chemokines involved in the
recruitment of monocytes/macrophages and activated lymphocytes. In this study we
addressed the expression and distribution of MCP-1, -2 and -3 in multiple
sclerosis (MS) lesions of differing ages and levels of inflammatory activity
using immunohistochemistry and in situ hybridization. In acute and chronic-active
MS lesions immunoreactivity for MCP-1, -2 and -3 was prominent throughout the
lesion center with reactivity diminishing abruptly at the lesion edge.
Hypertrophic astrocytes were strongly reactive and inflammatory cells showed
variable reactivity. Outside of the lesion only hypertrophic astrocytes were
reactive. The results obtained by in situ hybridization for MCP-1 were in
agreement with those obtained by immunostaining. In more chronic lesions
immunoreactivity for MCP-1, -2 and -3 was considerably diminished, and in chronic
silent lesions immunoreactivity was restricted to a few scattered reactive
astrocytes. Normal control brains showed no immunoreactivity for MCP-1, -2 and
3. Although the cellular distribution of all three members of this family was
similar, antibodies to MCP-3 gave prominent staining of the extracellular matrix
that was not noted for MCP-1 and -2. These results support the conclusion that
members of the MCP family of chemokines are involved in the development of MS
lesions in the central nervous system.
PMID- 9655470
TI - Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys
(Callithrix jacchus).
AB - Accessory molecules and cytokines are involved in the immunopathogenesis of
multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in
rodent models, and are potential targets for immunotherapy. Evaluation of such
experimental therapies requires appropriate animal models. Therefore, we analysed
the expression of selected accessory molecules and cytokines in the brain of
marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human
primate model for MS. All animals experienced active disease clinically and
histopathologically with strong resemblance to MS. Perivascular infiltrates of
mononuclear cells showed abundant expression of CD40. CD40 was expressed on
macrophages, indicating that T cell priming and macrophage effector functions may
result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86)
were also expressed, but to a lower extent, while B7-1 (CD80) expression was
limited. Both pro-inflammatory and anti-inflammatory cytokines were produced
within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha,
IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative
levels rather than sequential expression of Th1- and Th2-type cytokines determine
disease activity. These findings demonstrate the value of EAE in marmoset monkeys
as a model to assess the role of accessory molecules and cytokines in multiple
sclerosis, and to evaluate targeted intervention.
PMID- 9655471
TI - Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced
apoptosis and improves survival in a murine glioma model.
AB - We have previously reported that local secretion of either TNF-alpha or TGF beta1
by intracerebral SMA-560 malignant glioma tumor cells can reduce or eliminate
tumor growth in mice. However, the use of TNF-alpha, while improving the overall
survival of tumor bearing animals, was associated with early toxic deaths due to
cerebral edema. In the present study, we demonstrate that TNF-alpha induces
apoptosis of the SMA 560 cell line, as does TGF beta1, and that these two
cytokines act in an additive fashion to enhance apoptosis and thus, to inhibit
SMA 560 cell growth in vitro. Next, we show that the production of TGF beta1 when
added to TNF-alpha production by central nervous system tumors in vivo abrogates
any early deaths seen due to TNF-alpha toxicity and leads to a larger percentage
of animals surviving CNS tumor challenge. Finally, we demonstrate that the
production of TGF beta1 by tumor cells is associated with the abolition of tumor
associated cerebral edema in both TNF-alpha and in non-TNF-alpha producing
tumors. These results are important for the development of effective and less
toxic therapies for brain tumors, as well as for examining the pathogenesis of
tumor-related cerebral edema.
PMID- 9655472
TI - Induction of primary immune responses by allogeneic human myoblasts: dissection
of the cell types required for proliferation, IFNgamma secretion and
cytotoxicity.
AB - Non-professional antigen-presenting cells (APC) have a limited ability to
activate T lymphocytes during normal and auto-immune responses. Myoblasts could
play an important role as APC in the etiology of autoimmune myasthenia gravis and
polymyositis, as well as during muscle graft rejection. We examined the role of
different component cell subsets in the response of human peripheral blood
mononuclear cells (PBMC) to allogeneic myoblasts. Treatment of myoblasts with
TNFalpha or IFNgamma led to the expression of a range of immunostimulatory
molecules including MHC class I and II, and CD95 (Fas), but not B7 family
molecules. Whole PBMC, cultured with allogeneic myoblasts, proliferated, secreted
IFNgamma, and were cytotoxic. Proliferation and IFNgamma secretion were largely
dependent on the presence of CD4+ lymphocytes, but neither CD4+ nor CD8+ T cells
were responsible for cytotoxicity, which was mediated by MHC class II+ non-T
mononuclear cells. However, purified CD4+ lymphocytes co-cultured with allogeneic
myoblasts required co-stimulation with anti-CD28 antibodies for proliferation and
IFNgamma secretion, which only induced a low level of IFNgamma secretion by CD8+
lymphocytes and did not induce cytotoxic function. These results suggest that
human myoblasts can act as antigen-presenting cells for naive T lymphocytes, but
only with additional co-stimulation.
PMID- 9655473
TI - Selective reduction in CD2 expression on CD2bright/CD8+ lymphocytes from
cynomolgus monkeys (Macaca fascicularis) in response to acute stress.
AB - Numerous reports have demonstrated a link between stressful stimuli and immune
suppression. However, the cellular mechanisms by which stress impairs immune
function are largely unknown. We have examined the effects of an acute stressor
on the T cell population, specifically, the number and phenotype of T cells in a
nonhuman primate model. In nonstressed adult monkeys, we found differences in the
level of expression of CD2 on T cells, revealing two distinct subsets of T cells,
CD2dim and CD2bright cells, with CD2bright cells predominately coexpressing CD8.
In response to acute stress, we observed a significant loss in the number and
percent of CD2bright/CD8+ cells, with percent of CD2bright cells returning to pre
stress values within 24 h.
PMID- 9655474
TI - Is IgG anti-GT1a antibody associated with pharyngeal-cervical-brachial weakness
or oropharyngeal palsy in Guillain-Barre syndrome?
AB - The pharyngeal-cervical-brachial variant (PCB) of Guillain-Barre syndrome (GBS)
has clinical features similar to those of botulism and diphtheria. Mizoguchi et
al. (1994) [Mizoguchi, K., Hase, A., Obi, T., Matsuoka, H., Takatsu, M.,
Nishimura, Y., Irie, F., Seyama, Y., Hirabayashi, Y., 1994. Two species of
antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial
variant of Guillain-Barre syndrome. J. Neurol. Neurosurg. Psychiatry 57, 1121
1123] reported a patient with PCB-like symptoms who had serum IgG anti-GT1a
antibodies which did not cross-react with GQ1b. We assumed that PCB is associated
with anti-GT1a antibodies that do not have reactivity to GQ1b and made a
serological study of a PCB patient. We searched for PCB patients prospectively
and found one with PCB. This patient had IgG anti-GT1a antibodies which were not
absorbed with GQ1b in an absorption study, whereas IgG anti-GT1a antibodies from
Fisher's syndrome patients were. The frequency of positive IgG anti-GT1a antibody
did not differ in patients with and without bulbar palsy. Our findings indicate
that IgG anti-GT1a antibodies which do not cross-react with GQ1b are specifically
detectable in PCB and can be used as a diagnostic marker of PCB.
PMID- 9655475
TI - Human lymphocytes express substance P and its receptor.
AB - We present data demonstrating the gene expression of substance P (SP) and its
receptor in human peripheral blood-isolated lymphocytes. Using reverse
transcribed polymerase chain reaction (RT-PCR) assay, preprotachykinin-A
(substance-P) mRNA is detected in human peripheral blood-isolated lymphocytes.
Among the alpha, beta, and gamma transcripts of the SP gene, only the beta and
gamma transcripts are detectable in these cells. These RT-PCR amplified
transcripts are recognized by Southern blot assay using a specific SP probe.
Direct DNA sequence analysis of the RT-PCR products from lymphocytes also
confirmed the structure of these transcripts which are identical to those found
in human neuronal cells. At the protein level, human lymphocytes produced
endogenous SP as determined by an enzyme immunoassay. Capsaicin, a vanillyl fatty
acid amide (ingredient of hot pepper), released preformed SP from lymphocytes. In
addition, using RT/nested-PCR analysis, we identified the presence of mRNA for
neurokinin-1 receptor (the receptor for SP) in human peripheral blood-isolated
lymphocytes, which was confirmed by Southern blot and DNA sequencing analysis.
The demonstration that human lymphocytes express SP and its receptor support the
notion that SP is biologically involved in regulating the functions of these
cells in an autocrine fashion.
PMID- 9655476
TI - Specific binding of a 125I-secretoneurin analogue to a human monocytic cell line.
AB - Secretoneurin (SN) is a novel neuropeptide expressed in the central and
peripheral nervous system as well as in various endocrine tissues. SN inhibits
growth of aortic pulmonary and endothelial cells and is a potent chemoattractant
for endothelial cells, skin fibroblasts and monocytes. We investigated here the
presence of specific high affinity binding sites for SN on a target tissue. SN
was iodinated with the Bolton-Hunter (BH) reagent and purified by isocratic
reversed phase chromatography. Specific binding sites for 125I-BHSN were
identified on human Mono Mac 6 cells, a monocytic cell line. Scatchard analysis
revealed a single class of binding sites with a Kd value of 7.3 nM and a Bmax of
322 (fmol/mg protein). Competition studies demonstrated that the 15 C-terminal
amino acids of SN could displace authentic SN, whereas shorter fragments were
inactive. Other sensory neuropeptides like substance P, calcitonin gene-related
peptide or galanin as well as the chemokine receptor ligand Rantes or the typical
chemoattractant FMLP could not displace SN. Our studies demonstrate specific high
affinity binding sites for SN on a monocytic cell line. Since SN exerts a potent
chemotactic activity towards monocytes and increases cytosolic calcium in these
cells, these binding sites might well represent a putative functional plasma
membrane receptor for SN.
PMID- 9655477
TI - Pathogenesis of acute passive murine encephalomyelitis I. Importance of host
derived cells as determined by kinetic analysis.
AB - Kinetics of entry into the CNS of donor- and host-derived T-cells during the
onset of acute murine EAE induced by the passive transfer of an encephalitogenic
PLP(139-151)-specific T-cell clone was investigated. RT-PCR and spectratypic
analysis of total RNA recovered from recipient mice demonstrated the presence in
the CNS of donor- and host-derived T-cells 24 h post adoptive transfer. Donor
derived T-cells detected in the CNS decreased days 2-6 post transfer while host
derived T-cells persisted during this time. Beginning 3 days before clinical
onset, an increase in the CNS of both T-cell populations was observed which
persisted through disease onset. Similar analysis performed on recipients of an
nonencephalitogenic PLP(139-151)-specific T-clone demonstrated a transient
infiltration of donor- and host-derived T-cells beginning 4 days post transfer
(dpt) and returning to background levels by day 7 post transfer. Results
presented here suggest the importance of host-derived T-cells in the onset of
acute passive murine EAE.
PMID- 9655478
TI - Endotoxin stimulates an endogenous pathway regulating corticotropin-releasing
hormone and vasopressin release involving the generation of nitric oxide and
carbon monoxide.
AB - Although the administration of endotoxin in vivo activates the neuroendocrine
stress axis in the process of crosstalk between the immune and endocrine axes,
the direct application of endotoxin to the hypothalamus in vitro does not
stimulate the release of the hypothalamic peptides controlling the hypothalamo
pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and
vasopressin. The hypothesis has therefore been tested that endotoxin may also
activate inhibitory pathways, specifically those involving the generation of
nitric oxide (NO) and carbon monoxide (CO). Studies were performed on the
isolated rat hypothalamus using endotoxin in the presence or absence of
inhibitors of heme oxygenase (which generates CO) and nitric oxide synthase, and
ferrous hemoglobin. Endotoxin alone decreased both CRH and vasopressin secretion
from the hypothalamus. However, when applied together with a nitric oxide
synthase inhibitor, the inhibitory effect on CRH was lost. Conversely, co
administration with heme oxygenase inhibitors transformed the inhibition of
vasopressin to stimulation, while having no effect on the inhibition of CRH.
Ferrous hemoglobin reversed the inhibition of vasopressin, but did not lead to
stimulation. It is therefore concluded that endotoxin may stimulate endogenous
pathways that lead to the generation of NO, which in turn inhibits CRH. In
addition, it generates CO, which modulates the release of vasopressin. These
gases are thus potential counter-regulatory controls to the activation of the
HPA.
PMID- 9655479
TI - Heat shock proteins come of age: primitive functions acquire new roles in an
adaptive world.
PMID- 9655480
TI - Induction of rapid T cell activation and tolerance by systemic presentation of an
orally administered antigen.
AB - To understand how orally introduced antigen regulates peripheral immune
responses, we fed cytochrome c protein to mice transgenic for the beta chain of a
cytochrome c-specific TCR and followed the antigen-specific T cell responses with
a cyt c/I-Ek tetramer staining reagent. We find that within 6 hr of cytochrome c
administration, antigen-specific systemic T cell activation is induced, and
spleen cells gain the ability to stimulate cytochrome c-specific T cell
responses. Feeding multiple low doses of cytochrome c down-regulates the systemic
immune response, which can be correlated with a reduction of antigen-specific T
cells and not with immune deviation. These results suggest that systemic
distribution of antigen contributes significantly to oral tolerance induction.
PMID- 9655481
TI - Detection of antigen-specific T cells with multivalent soluble class II MHC
covalent peptide complexes.
AB - Multimeric soluble MHC class II molecules stably occupied with covalently
attached peptides bind with appropriate specificity to T cell hybridomas and T
cells from T cell receptor transgenic mice. There is a direct correlation between
soluble T cell receptor affinity for monomeric MHC/peptide and level of binding
of multimeric MHC/peptide to T cells. While binding of the multimeric MHC/peptide
complex is proportional to T cell receptor affinity and expression level, there
is little influence of T cell CD4.
PMID- 9655482
TI - Virus-specific CD8+ T cells in primary and secondary influenza pneumonia.
AB - Virus-specific CD8+ effector T cells (eCTL) are enriched in the lungs of mice
with primary influenza pneumonia, though later detection of memory T cells (mCTL)
in the mediastinal lymph nodes (MLN) or spleen by peptide-based staining
protocols is at the limits of flow cytometric analysis. Respiratory challenge
with an H3N2 virus months after H1N1 priming induces a massive recall response,
which reduces virus titers 2-3 days earlier than in nave controls. Influenza
specific mCTL produce interferon-gamma within 6 hr, but still take 4-5 days to
localize to the infected respiratory tract. The delay reflects that the recall
response develops first in the MLN, which contains relatively few mCTL. The
response to a subdominant epitope is less obvious after secondary challenge.
PMID- 9655483
TI - Association of DAP12 with activating CD94/NKG2C NK cell receptors.
AB - While the inhibitory NK cell receptors for MHC class I express immunoreceptor
tyrosine-based inhibitory motifs that recruit intracellular tyrosine phosphatases
and prevent NK cell effector function, the activating NK cell receptors lack
intrinsic sequences required for cellular stimulation. CD94/NKG2C, an activating
NK cell receptor of the C-type lectin superfamily that binds to HLA-E,
noncovalently associates with DAP12, a membrane receptor containing an
immunoreceptor tyrosine-based activating motif. Efficient expression of
CD94/NKG2C on the cell surface requires the presence of DAP12, and charged
residues in the transmembrane domains of DAP12 and NKG2C are necessary for this
interaction. These results provide a molecular basis for the assembly of NK cell
receptors for MHC class I involved in cellular activation and inhibition.
PMID- 9655484
TI - Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes.
AB - Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal
transduction pathway and serves as a common target for the immunosuppressants
FK506 and cyclosporin A. We report the identification of a novel endogenous
calcineurin binding protein named Cabin 1 that inhibits calcineurin-mediated
signal transduction. The interaction between Cabin 1 and calcineurin is dependent
on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants
inhibits the transcriptional activation of calcineurin-responsive elements in the
interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell
activation. These results suggest a negative regulatory role for Cabin 1 in
calcineurin signaling and provide a possible mechanism of feedback inhibition of
TCR signaling through cross-talk between protein kinases and calcineurin.
PMID- 9655485
TI - T cell receptor gamma gene regulatory sequences prevent the function of a novel
TCRgamma/pTalpha pre-T cell receptor.
AB - Expression of a TCRgamma transgene in RAG-1-/- mice resulted in the development
of a limited number of CD4+CD8+ (DP) thymocytes. In vivo treatments with anti
TCRgamma antibody enhanced the number of DP thymocytes, demonstrating that
TCRgamma chains were expressed on the cell surface in the absence of delta,
alpha, or beta chains. Mutations in pTalpha or CD3epsilon genes abolished
transgene-induced DP cell development, indicating that TCRgamma can associate
with pTalpha and CD3 to form a novel pre-TCR. With a transgene containing
additional regulatory sequences, TCRgamma expression was down-regulated in DP
cells, and little DP cell development occurred. Thus, the function of the
endogenous TCRgamma/pTalpha is limited by the transcriptional down-regulation of
TCRgamma genes that normally accompanies DP cell development.
PMID- 9655486
TI - Membrane compartmentation is required for efficient T cell activation.
AB - The plasma membrane of mammalian cells contains detergent-resistant membrane
rafts enriched in glycosphingolipids and cholesterol. Although several important
signaling molecules have been found in such rafts, evidence documenting a
functional role for their localization has been scarce. Using a fractionation
scheme that preserves tyrosine phosphorylation, we show that T cell activation
leads to a striking compartmentation in the rafts of activated T cell receptor
and associated signal-transducing molecules. Conditions that reversibly disrupt
raft structure either by dispersing their contents or by forcing their
internalization reversibly disrupt the earliest steps of T cell activation. Thus,
raft integrity is a prerequisite for efficient T cell receptor signal
transduction.
PMID- 9655487
TI - Arrest of B lymphocyte terminal differentiation by CD40 signaling: mechanism for
lack of antibody-secreting cells in germinal centers.
AB - Despite extensive research, the role of CD40 signaling in B cell terminal
differentiation remains controversial. Here we show that CD40 engagement arrests
B cell differentiation prior to plasma cell formation. This arrest is manifested
at a molecular level as a reduction in mRNA levels of secretory immunoglobulin
gene products such as mu(s) and J chain as well as the loss of the
transcriptional regulator BLIMP-1. Furthermore, the inhibition of B cell
differentiation by CD40 engagement could not be overcome by either mitogens or
cytokines, but could be reversed by antibodies that interfere with the CD40/gp39
interaction. These data suggest that secretory immunoglobulin is not produced by
B cells that are actively engaged by gp39-expressing T cells.
PMID- 9655488
TI - Reevaluation of 3'Ekappa function in stage- and lineage-specific rearrangement
and somatic hypermutation.
AB - Transgenic studies have led to the conclusion that the 3'Ekappa enhancer
functions to suppress kappa variable region gene assembly in T lineage cells and
in progenitor B cells and have also implicated 3'Ekappa as a critical element in
promoting somatic hypermutation of kappa variable region genes. To assess the
role of the endogenous 3'Ekappa, we assayed these processes in mice homozygous
for mutations in which the 3'Ekappa sequences were deleted by the loxP/Cre method
(3'Ekappa delta/delta mice). In contrast to transgenic findings, we found that
deletion of the endogenous 3'Ekappa did not deregulate kappa gene rearrangement
in T lineage cells or in pro-B cells. Furthermore, immunization of the 3'Ekappa
delta/delta mice led to the generation of specific antibodies with mutation
patterns typical of affinity maturation, showing that there is no absolute
requirement for the 3'Ekappa with respect to somatic mutation of endogenous kappa
genes.
PMID- 9655489
TI - Affinity dependence of the B cell response to antigen: a threshold, a ceiling,
and the importance of off-rate.
AB - Initiation and affinity maturation of the humoral immune response is driven by
antigen interaction with BCR. To study how signaling and antigen presentation
through BCR depend on antigen/BCR affinity, lysozyme-specific B cell
transfectants were challenged with mutated lysozymes differing in their binding
kinetics. For detectable triggering, the antigen/BCR complex needed a Ka > 10(6)
M(-1) (dissociation half-life > approximately 1 s). Mutated lysozymes whose
binding was below this threshold could nevertheless be presented if complexed
with soluble antibody. Above the threshold, the concentration of antigen required
to trigger a response decreased as the affinity (particularly dissociation half
life) increased. However, a plateau was reached at Kas > approximately 10(10) M(
1) (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to
affinity maturation.
PMID- 9655490
TI - In vitro generation of lymphohematopoietic cells from endothelial cells purified
from murine embryos.
AB - We have investigated the lymphohematopoietic potentials of endothelial cells (EC)
and hematopoietic cells (HPC) sorted from embryos. Expression of VE-cadherin,
CD45, and Ter119 was used to distinguish EC (VE-cadherin+CD45-Ter119-) from HPC
(VE-cadherin-CD45+). Thus defined, EC population takes up acetylated LDL and
coexpresses CD31, Flk1, and CD34. In E9.5 embryos, EC from yolk sac (YS) and the
embryo proper generate blood cells, including lymphocytes. Thus,
lymphohematopoietic EC do exist in the embryo, and they are generated both in YS
and the embryo proper. On the other hand, HPC with lymphopoietic potency appear
first in the embryo proper. These findings implicate involvement of multiple
environmental cues for acquiring lymphopoietic competency during differentiation
of HPC.
PMID- 9655491
TI - Innate immune recognition of bacterial lipopolysaccharide: dependence on
interactions with membrane lipids and endocytic movement.
AB - Lipopolysaccharide ([LPS], an endotoxin) from most bacterial species provokes a
strong inflammatory response in naive animals. LPS from Rhodobacter sphaeroides
(RsLPS) has a relatively small hydrophobic region and does not stimulate cells or
animals but instead acts as antagonist of LPS action. Here, we show that the
activity of RsLPS is transformed from antagonist to full agonist by the addition
of chlorpromazine (CPZ) and other cationic membrane-active agents. In addition,
while LPS is rapidly transported from the plasma membrane to an intracellular
site, we find that RsLPS is not transported but instead remains in the cell
periphery. Addition of CPZ also reverses this behavior, causing RsLPS to be
transported to a perinuclear site. The data suggest that the interaction of LPS
with membrane lipids is influenced by membrane-modifying agents such as CPZ, and
these interactions dictate both its intracellular transport and its ability to
stimulate cellular responses.
PMID- 9655492
TI - fMRI of monkey visual cortex.
AB - While functional magnetic resonance imaging (fMRI) is now used widely for
demonstrating neural activity-related signals associated with perceptual, motor,
and cognitive processes in humans, to date this technique has not been developed
for use with nonhuman primates. fMRI in monkeys offers a potentially valuable
experimental approach for investigating brain function, which will complement and
aid existing techniques such as electrophysiology and the behavioral analysis of
the effects of brain lesions. There are, however, a number of significant
technical challenges involved in using fMRI with monkeys. Here, we describe the
procedures by which we have overcome these challenges to carry out successful
fMRI experiments in an alert monkey, and we present the first evidence of
activity-related fMRI signals from monkey cerebral cortex.
PMID- 9655493
TI - Synaptic adhesion: the building blocks of memory?
PMID- 9655494
TI - Null mutations lacking substance: elucidating pain mechanisms by genetic
pharmacology.
PMID- 9655495
TI - Experience-dependent plasticity and the maturation of glutamatergic synapses.
PMID- 9655496
TI - Genes, brain, and mind: the evolution of cognition.
PMID- 9655497
TI - Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed
by dynamic imaging in living zebrafish embryos.
AB - In the vertebrate olfactory system, sensory neurons with common odorant
specificities project to specific glomeruli in the olfactory bulb. How do
olfactory sensory neurons find their glomerular targets? To address this
question, we have visualized the genesis of the peripheral olfactory system in
living zebrafish embryos. Dye labelings reveal that a primordial yet stereotyped
map of glomeruli is apparent during embryogenesis. By labeling a small number of
cells with an ectopically expressed green fluorescent protein reporter, we can
observe the dynamic growth behaviors of individual olfactory neuron growth cones
as they project to their glomeruli. We find that olfactory axons extend directly
to their partner glomeruli, suggesting that these cells' growth cones rely upon
pathfinding cues to reach their targets.
PMID- 9655498
TI - Corticotropin releasing factor receptor 1-deficient mice display decreased
anxiety, impaired stress response, and aberrant neuroendocrine development.
AB - Corticotropin releasing factor (CRF) is a major integrator of adaptive responses
to stress. Two biochemically and pharmacologically distinct CRF receptor subtypes
(CRFR1 and CRFR2) have been described. We have generated mice null for the CRFR1
gene to elucidate the specific developmental and physiological roles of CRF
receptor mediated pathways. Behavioral analyses revealed that mice lacking CRFR1
displayed markedly reduced anxiety. Mutant mice also failed to exhibit the
characteristic hormonal response to stress due to a disruption of the
hypothalamic-pituitary-adrenal (HPA) axis. Homozygous mutant mice derived from
crossing heterozygotes displayed low plasma corticosterone concentrations
resulting from a marked agenesis of the zona fasciculata region of the adrenal
gland. The offspring from homozygote crosses died within 48 hr after birth due to
a pronounced lung dysplasia. The adrenal agenesis in mutant animals was
attributed to insufficient adrenocorticotropic hormone (ACTH) production during
the neonatal period and was rescued by ACTH replacement. These results suggest
that CRFR1 plays an important role both in the development of a functional HPA
axis and in mediating behavioral changes associated with anxiety.
PMID- 9655499
TI - Three period homologs in mammals: differential light responses in the
suprachiasmatic circadian clock and oscillating transcripts outside of brain.
AB - We have cloned and characterized the mouse cDNA of a third mammalian homolog of
the Drosophila period gene and designated it mPer3. The mPER3 protein shows
approximately 37% amino acid identity with mPER1 and mPER2 proteins. The three
mammalian PER proteins share several regions of sequence homology, and each
contains a protein dimerization PAS domain. mPer3 RNA levels oscillate in the
suprachiasmatic nuclei (SCN) and eyes. In the SCN, mPer3 RNA levels are not
acutely altered by light exposure at different times during subjective night.
This contrasts with the acute induction by light of mPer1 and mPer2 RNA levels
during early and late subjective night. mPer3 is widely expressed in tissues
outside of brain. In liver, skeletal muscle, and testis, mPer RNAs exhibit
prominent, synchronous circadian oscillations. The results highlight the
differential light responses among the three mammalian Per genes in the SCN and
raise the possibility of circadian oscillators in mammals outside of brain and
retina.
PMID- 9655500
TI - Subunit composition, protein interactions, and structures of the mammalian brain
sec6/8 complex and septin filaments.
AB - Both the sec6/8 complex and septin filaments have been implicated in directing
vesicles and proteins to sites of active membrane addition in yeast. The rat
brain sec6/8 complex coimmunoprecipitates with a filament composed of four
mammalian septins, suggesting an interaction between these complexes. One of the
septins, CDC10, displays broad subcellular and tissue distributions and is found
in postmitotic neurons as well as dividing cells. Electron microscopic studies
showed that the purified rat brain septins form filaments of 8.25 nm in diameter;
the lengths of the filaments are multiples of 25 nm. Glutaraldehyde-fixed rat
brain sec6/8 complex adopts a conformation resembling the letter "T" or "Y". The
sec6/8 and septin complexes likely play an important role in trafficking vesicles
and organizing proteins at the plasma membrane of neurons.
PMID- 9655501
TI - Real time imaging of calcium-induced localized proteolytic activity after axotomy
and its relation to growth cone formation.
AB - The emergence of a neuronal growth cone from a transected axon is a necessary
step in the sequence of events that leads to successful regeneration. Yet, the
molecular mechanisms underlying its formation after axotomy are unknown. In this
study, we show by real time imaging of the free intracellular Ca2+ concentration,
of proteolytic activity, and of growth cone formation that the activation of
localized and transient Ca2+-dependent proteolysis is a necessary step in the
cascade of events that leads to growth cone formation. Inhibition of this
proteolytic activity by calpeptin, a calpain inhibitor, abolishes growth cone
formation. We suggest that calpain plays a central role in the reorganization of
the axon's cytoskeleton during its transition from a stable differentiated
structure into a dynamically extending growth cone.
PMID- 9655502
TI - Diversity revealed by a novel family of cadherins expressed in neurons at a
synaptic complex.
AB - In mammals, neurons are highly differentiated and play distinctive functions even
in the same brain region. We found a novel cadherin-related neuronal receptor
(Cnr) gene family by studying Fyn-binding activity in mouse brain. CNR1 protein
is located in the synaptic junction and forms a complex with Fyn. Sequence
analysis of eight Cnr products of approximately 20 genes indicates that these
comprise a novel cadherin family of the cadherin superfamily. The expression
patterns of each member of this novel family were grossly similar to each other
but restricted to subpopulations of neurons of the same type. The diversity of
the Cnr family genes suggests that there are molecular mechanisms that govern
highly differentiated neural networks in the mammalian CNS.
PMID- 9655503
TI - Structure-function analysis of cell adhesion by neural (N-) cadherin.
AB - To investigate the possible biological function of the lateral "strand dimer"
observed in crystal structures of a D1 domain extracellular fragment from N
cadherin, we have undertaken site-directed mutagenesis studies of this molecule.
Mutation of most residues important in the strand dimer interface abolish the
ability of N-cadherin to mediate cell adhesion. Mutation of an analogous central
residue (Trp-2) in E-cadherin also abrogates the adhesive capacity of that
molecule. We also determined the crystal structure of a Ca2+-complexed two-domain
fragment from N-cadherin. This structure, like its E-cadherin counterpart, does
not adopt the strand dimer conformation. This suggests the possibility that
classical cadherins might stably exist in both dimeric and monomeric forms. Data
from several laboratories imply that lateral dimerization or clustering of
cadherins may increase their adhesivity. We suggest the possibility that the
strand dimer may play a role in this activation.
PMID- 9655504
TI - A role for the cadherin family of cell adhesion molecules in hippocampal long
term potentiation.
AB - The cadherins are a family of cell-cell adhesion molecules that mediate Ca2+
dependent homophilic interactions between cells and transduce signals by
interacting with cytoplasmic proteins. In the hippocampus, immunostaining
combined with confocal microscopy revealed that both neural- (N-) and epithelial-
(E-) cadherin are present at synaptic sites, implying a role in synaptic
function. Pretreatment of hippocampal slices with antibodies (Abs) raised against
the extracellular domain of either N-cad or E-cad had no effect on basal synaptic
properties but significantly reduced long-term potentiation (LTP). Infusion of
antagonistic peptides containing the His-Ala-Val (HAV) consensus sequence for
cadherin dimerization also attenuated LTP induction without affecting previously
established LTP. Because the intense synaptic stimulation associated with LTP
induction might transiently deplete extracellular Ca2+ and hence potentially
destabilize cadherin-cadherin interactions, we examined whether slices could be
protected from inhibition by N-cad Abs or HAV peptides by raising the
extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+
prevented the block of LTP by these agents. Taken together, these results
indicate that cadherins are involved in synaptic plasticity, and the stability of
cadherin-cadherin bonds may be regulated by synaptic stimulation.
PMID- 9655505
TI - Strength and orientation tuning of the thalamic input to simple cells revealed by
electrically evoked cortical suppression.
AB - Is thalamic input to the visual cortex strong and well tuned for orientation, as
predicted by Hubel and Wiesel's (1962) model of orientation selectivity in simple
cells? We directly measured the size of the thalamic input to single simple cells
intracellularly by combining electrical stimulation of the cortex with a briefly
flashed visual stimulus. In nearby cells, the electrical stimulation evoked a
long-lasting inhibition that prevented them from firing in response to the visual
stimulus. The visually evoked excitatory postsynaptic potentials (EPSPs) recorded
during the period of cortical suppression, therefore, reflected largely the
thalamic input. In 16 neurons that received monosynaptic input from the thalamus,
cortical suppression left 46% of normal visual response on average (12%-86% in
range). In those cells tested, this remaining visual response was as well tuned
for orientation as the normal response to the visual stimulus alone. We conclude
that the thalamic input to cortical simple cells with monosynaptic input from the
thalamus is strong and well tuned in orientation, and that the intracortical
input does not appear to sharpen orientation tuning in these cells.
PMID- 9655506
TI - Attention and perceptual learning modulate contextual influences on visual
perception.
AB - Brightness discrimination thresholds and facilitation by lateral interaction were
measured in five human observers and two monkeys. The subjects judged the
brightness of one of four peripherally seen lines against a reference. This
experiment was performed both when the observer was cued to the position of the
test line (focused attention) and when there was no cue (distributed attention).
Discrimination was better with focused than with distributed attention. When the
test line had a collinear flank, its brightness was enhanced; this enhancement
was four times more prominent with distributed than with focused attention. After
training, thresholds improved and collinear facilitation decreased under
distributed but not under focused attention. The findings show that there are
fewer benefits from contextual interaction once attention is directed toward a
visual location, and that the attentional effects are subject to training.
PMID- 9655507
TI - Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant
mice.
AB - Activation of adenylyl cyclase and the consequent production of cAMP is a process
that has been shown to be central to invertebrate model systems of information
storage. In the vertebrate brain, it has been suggested that a presynaptic
cascade involving Ca influx, cAMP production, and subsequent activation of cAMP
dependent protein kinase is necessary for induction of long-term potentiation
(LTP) at the cerebellar parallel fiber-Purkinje cell synapse. We have used mutant
mice in which the major Ca-sensitive adenylyl cyclase isoform of cerebellar
cortex (type I) is deleted to show that this results in an approximately 65%
reduction in cerebellar Ca-sensitive cyclase activity and a nearly complete
blockade of cerebellar LTP assessed using granule cell-Purkinje cell pairs in
culture. This blockade is not accompanied by alterations in a number of basal
electrophysiological parameters and may be bypassed by application of an
exogenous cAMP analog, suggesting that it results specifically from deletion of
the type I adenylyl cyclase.
PMID- 9655508
TI - Kainate receptor modulation of GABA release involves a metabotropic function.
AB - The mechanism through which kainate receptors downregulate the release of GABA in
the hippocampus is not known. We have found that the action of kainate on the
hippocampal inhibitory postsynaptic current (IPSC) is mediated by a metabotropic
process that is sensitive to Pertussis toxin (PTx) and independent of ion channel
current. The downregulation of GABA IPSCs by kainate was also prevented in a dose
dependent manner by calphostin C, a specific inhibitor of PKC, and the inhibition
of phospholipase C (PLC) drastically reduced the action of kainate. The effect of
kainate was completely occluded by phorbol esters and by increasing extracellular
Ca2+ but remained unaltered after inhibition or activation of protein kinase A
(PKA). These results demonstrate that the activation of kainate receptors
triggers a second messenger cascade, which results in the stimulation of PKC, and
therefore document a metabotropic action of kainate receptors, which results in
the inhibition of GABA release.
PMID- 9655509
TI - Synaptic defects and compensatory regulation of inositol metabolism in inositol
polyphosphate 1-phosphatase mutants.
AB - Phosphoinositides function as important second messengers in a wide range of
cellular processes. Inositol polyphosphate 1-phosphatase (IPP) is an enzyme
essential for the hydrolysis of the 1-phosphate from either Ins(1,4)P2 or
Ins(1,3,4)P3. This enzyme is Li+ sensitive, and is one of the proposed targets of
Li+ therapy in manic-depressive illness. Drosophila ipp mutants accumulate IP2 in
their system and are incapable of metabolizing exogenous Ins(1,4)P2. Notably, ipp
mutants demonstrate compensatory upregulation of an alternative branch in the
inositol-phosphate metabolism tree, thus providing a means of ensuring continued
availability of inositol. We demonstrate that ipp mutants have a defect in
synaptic transmission resulting from a dramatic increase in the probability of
vesicle release at larval neuromuscular junctions. We also show that Li+
phenocopies this effect in wild-type synapses. Together, these results support a
role for phosphoinositides in synaptic vesicle function in vivo and
mechanistically question the "lithium hypothesis."
PMID- 9655510
TI - The nematode degenerin UNC-105 forms ion channels that are activated by
degeneration- or hypercontraction-causing mutations.
AB - Nematode degenerins have been implicated in touch sensitivity and other forms of
mechanosensation. Certain mutations in several degenerin genes cause the
swelling, vacuolation, and death of neurons, and other mutations in the muscle
degenerin gene unc-105 cause hypercontraction. Here, we confirm that unc-105
encodes an ion channel and show that it is constitutively active when mutated.
These mutations disrupt different regions of the channel and have different
effects on its gating. The UNC-105 channels are permeable to small monovalent
cations but show voltage-dependent block by Ca2+ and Mg2+. Amiloride also
produces voltage-dependent block, consistent with a single binding site 65% into
the electric field. Mammalian cells expressing the mutant channels accumulate
membranous whorls and multicompartment vacuoles, hallmarks of degenerin-induced
cell death across species.
PMID- 9655511
TI - Cytosolic Ca2+ acts by two separate pathways to modulate the supply of release
competent vesicles in chromaffin cells.
AB - Recovery from depletion of the readily releasable pool of vesicles (RRP) in
adrenal chromaffin cells was studied at differing basal [Ca2+]i or following
protein kinase C (PKC) activation by phorbol esters. Following depletion, the
pool size was estimated at varied times from cell capacitance jumps in response
to paired depolarizations. The experimentally observed RRP recovery time course
and steady-state size could be predicted from the measured [Ca2+]i signal
assuming a Michaelis-Menten-type regulation of the vesicle supply by Ca2+. An
elevated recruitment activity was observed at increased [Ca2+]i even when protein
kinase C was blocked, but maximum effects could be obtained only after
stimulation of PKC by phorbol esters or by prolonged elevations in [Ca2+]i. We
suggest that, in chromaffin cells, elevated cytosolic Ca2+ modulates exocytotic
plasticity via PKC-dependent and -independent pathways.
PMID- 9655512
TI - Localized secretion of ATP and opioids revealed through single Ca2+ channel
modulation in bovine chromaffin cells.
AB - In bovine chromaffin cells, the Ca2+ channels involved in exocytosis are
effectively inhibited by ATP and opioids that are coreleased with catecholamines
during cell activity. This autocrine loop causes a delay in Ca2+ channel
activation that is quickly removed by preceding depolarizations. Changes in Ca2+
channel gating by secreted products thus make it possible to correlate Ca2+
channel activity to secretory events. Here, using cell-attached patch recordings,
we found a remarkable correlation between delayed Ca2+ channel openings and
neurotransmitter secretion induced by either local or whole-cell Ba2+
stimulation. The action is specific for N- and P/Q-type channels and largely
prevented by PTX and mixtures of purinergic and opioid receptor antagonists.
Overall, our data provide evidence that exocytosis, viewed through the autocrine
inhibition of non-L-type channels, is detectable in membrane patches of
approximately 1 microm2 distributed over 30%-40% of the total cell surface, while
Ca2+ channels and autoreceptors are uniformly distributed over most of the cell
membrane.
PMID- 9655513
TI - The location of the gate in the acetylcholine receptor channel.
AB - The cation-conducting channel of the nicotinic acetylcholine (ACh) receptor is
lined by the first (M1) and second (M2) membrane-spanning segments of each of its
five subunits. Six consecutive residues, alphaS239 to alphaT244, in the alpha
subunit M1-M2 loop and at the intracellular end of M2 were mutated to cysteine.
The accessibility of the substituted cysteines were probed with small, cationic,
sulfhydryl-specific reagents added extracellularly and intracellularly. In the
closed state of the channel, there is a barrier to these reagents added from
either side between alphaG240 and alphaT244. ACh induces the removal of this
barrier, which acts as an activation gate. The residues alphaG240, alphaE241,
alphaK242, and alphaT244 line a narrow part of the channel, in which this gate is
located.
PMID- 9655514
TI - Three transmembrane conformations and sequence-dependent displacement of the S4
domain in shaker K+ channel gating.
AB - We have acquired structural evidence that two components evident previously in
the depolarization-evoked gating currents from voltage-gated Shaker K+ channels
have their origin in sequential, two-step outward movements of the S4 protein
segments. A point mutation greatly destabilizes the "fully retracted" state of S4
transmembrane translocation, causing instead an intermediate state to predominate
at resting potentials. This state is distinguishable topologically and
fluorometrically. That a point mutation effectively excludes half the range of S4
motion from physiological voltages suggests that the diverse sensitivities among
voltage-gated channels might reflect not only differences in S4 valence, but also
displacement. Existence of an intermediate subunit state helps explain why
modeling channel activation has required positing greater than four closed
states.
PMID- 9655515
TI - Spatiotemporal measurement of free radical elimination in the abdomen using an in
vivo ESR-CT imaging system.
AB - Electron spin resonance (ESR) imaging can visualize the distribution of free
radicals in living systems according to their concentrations. However, the
application of ESR imaging to living animals has not been well established. Using
a rapid field scan L-band ESR imaging system, we have successfully obtained two
dimensional ESR projection (xz-plane projection) and three-dimensional ESR-CT
(trans-axial section along the y-axis) images of the abdomen of living mice after
an injection of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl
PROXYL) into the tail vein. The in vivo two-dimensional ESR projection imaging
clearly visualized the carbamoyl-PROXYL distribution and the rapid decay process
in the abdomen. Because among the viscera, the liver is most abundantly
associated with a blood volume, the outline of the image can be composed mainly
of this organ. We therefore attempted to find whether there will be a difference
in spatiotemporal dynamics of carbamoyl-PROXYL in the abdomens between the
control and the mice with liver damage by two-dimensional ESR projection. In the
control mice, carbamoyl-PROXYL was almost completely eliminated from the abdomen
within 5 minutes after administration. On the other hand, in mice with carbon
tetrachloride-damaged livers, the decay of carbamoyl-PROXYL was markedly
prolonged. Even at 5 min after administration, carbamoyl-PROXYL remained clearly
visible in the abdomen. In vivo three-dimensional ESR-CT imaging showed an even
distribution of carbamoyl-PROXYL throughout the whole liver, which corresponded
well with the images of trans-axial sections of the murine abdomen. We have
succeeded in displaying two-dimensional ESR projection and three-dimensional ESR
CT images of carbamoyl-PROXYL distribution and clearance in the abdomen of a
living animal. The ESR-CT imaging technique is considered to be a powerful new
tool for noninvasive investigations of the in vivo spatiotemporal dynamics of
free radical distribution and elimination in the organs.
PMID- 9655516
TI - Total antioxidant capacity of serum increased in early but not late period after
intestinal ischemia in rats.
AB - The ischemia of small intestine was induced in anesthetized Wistar rats by
occluding the superior mesenteric artery for 45 min and then the reperfusion was
set. Serum samples were obtained at the end of the ischemic period and also
during early (1 to 4 h) and late postischemic period (1 to 4 d). The total
antioxidant capacity (TRAP) of serum samples was evaluated using luminol enhanced
chemiluminescence. The increased mobilization of phagocytic cells and the release
of reactive oxygen species into the circulation was observed from the first and
second hour of the postischemic period, respectively. Nevertheless, the activity
of natural antioxidant mechanisms of serum was already elicited at the end of the
ischemic period. Furthermore, the TRAP of serum increased with the increasing
duration of early postischemic period. Among the antioxidants studied, urate and
ascorbate concentrations exerted the highest correlation with TRAP, but 31.6% of
the total antioxidant capacity remained for the activity of an unidentified
antioxidant(s). After being exhausted, the TRAP of serum oscillated around the
preoperation level at days 1-4 of the postischemic period. The increase in total
antioxidant capacity of serum induced by oxidative stress was sufficient to
prevent lipoperoxidation both in serum and intestinal tissue.
PMID- 9655517
TI - Quercetin glucosides interact with the intestinal glucose transport pathway.
AB - Flavonols are efficient antioxidants with the potential to protect biological
macromolecules from oxidative damage in vivo, and if absorbed into the
circulation they may protect against cardiovascular disease. Although flavonol
aglycones are present in foods at low concentrations, their glycosides are
abundant in onions, apples, beans and tea, and are thought to be stable under the
conditions of the human stomach and small bowel. There is, however, recent
evidence to suggest that intact glycosides of quercetin may be absorbed from the
small intestine by a mechanism involving the glucose transport pathway. In the
present study we tested this hypothesis by measuring the effect of quercetin
glycosides on the rate of efflux of galactose from the jejunal mucosa. Everted
sacs of rat jejunum preloaded with 14C-galactose were exposed to quercetin
glycosides isolated from onions. Quercetin mono- and diglucosides were shown to
accelerate the carrier-mediated efflux of galactose via a sodium-dependent
pathway. HPLC analysis confirmed the stability of the glycosides under conditions
simulating those in the upper alimentary tract. These studies suggest that
purified quercetin glucosides are capable of interacting with the sodium
dependent glucose transport receptors in the mucosal epithelium and may therefore
be absorbed by the small intestine in vivo.
PMID- 9655518
TI - Reoxygenation-induced mitochondrial damage is caused by the Ca2+-dependent
mitochondrial inner membrane permeability transition.
AB - Anoxia/reoxygenation injury of isolated rat liver mitochondria was investigated.
During anoxia of up to 60 min, the membrane potential was largely preserved and
mitochondrial swelling was not observed. Reoxygenation of anoxic mitochondria
rapidly caused swelling, cyclosporin A-sensitive Ca2+ efflux, [14C]sucrose
trapping, and loss of the membrane potential along with increased generation of
reactive oxygen intermediates (ROI). Although pretreatment with catalase and
superoxide dismutase completely abolished reoxygenation-induced generation of
ROI, mitochondrial damage was not prevented, as indicated by swelling, loss of
the membrane potential, a decrease of the ATP content, and cyclosporin A
sensitive Ca2+ efflux. However, addition of the immunosuppressant cyclosporin A
or addition of ADP completely prevented the mitochondrial damage induced by
reoxygenation. The same protective effect was noted when Ca2+ cycling was
prevented, either by chelating Ca2+ with EGTA or by inhibiting Ca2+ reuptake with
ruthenium red. These findings indicate that mitochondrial anoxia/reoxygenation
injury is caused by the cyclosporin A-sensitive and Ca2+-dependent membrane
permeability transition. In contrast, reoxygenation injury does not appear to be
triggered by the enhanced production of ROI.
PMID- 9655520
TI - 4-Hydroxynonenal modifies the effects of serum growth factors on the expression
of the c-fos proto-oncogene and the proliferation of HeLa carcinoma cells.
AB - In this study, the effect of 4-hydroxynonenal (HNE), a peroxidation product of
omega-6-poly-unsaturated fatty acids, on the expression of the c-fos proto
oncogene and growth factor-induced proliferation of HeLa carcinoma cells in vitro
was investigated. The Fos protein forms the heterodimer AP-1 with the Jun protein
and regulates the cell cycle by inducing cyclin D1. Agents that are able to
induce c-fos include serum, platelet-derived growth factor (PDGF), and epidermal
growth factor (EGF), all of which were used in this study. The proliferation rate
was determined by cell counting (viable and dead cells according to trypan blue
exclusion) and the BrdU assay. The c-fos mRNA level was monitored by the reverse
transcriptase/polymerase chain reaction. In the absence of HNE, serum-deprived
cells responded to serum stimulation with a more than 10-fold increase of the c
fos mRNA level as well as with an increased rate of DNA synthesis and cell
multiplication. Both EGF and PDGF (applied in combination with insulin) were able
to substitute for FCS and induced rapid growth of the tumor cells preincubated in
serum-deprived medium. In the absence of growth factors a negative correlation
between the HNE concentration (range: 1-250 microM) and the c-fos mRNA level was
observed. We suppose that HNE interferes in this case with the basal activity of
the c-fos promoter. EGF, when applied after the HNE treatment, induced rapid
growth of the tumor cells preincubated in serum-free medium, if HNE was used in a
physiological concentration (1 microM). No difference was observed compared to
the HNE-free control. c-fos mRNA level was nearly unchanged. In contrast, a
cytotoxic concentration of the aldehyde (100 microM) caused a complete inhibition
of proliferation, although a twofold increase of the c-fos mRNA level immediately
after the aldehyde treatment was observed. A similar effect of HNE in cytotoxic
concentration on c-fos expression was observed when cells were grown in presence
of PDGF instead of EGF. Hence, in both cases HNE possibly interferes with the
signal transduction pathway, which is initiated by external growth factors. The
increased c-fos expression might be part of an abortive attempt to overcome the
stressful condition raised by a cytotoxic concentration of HNE.
PMID- 9655519
TI - Chemical analysis of multiple sclerosis lesions by FT-IR microspectroscopy.
AB - Fourier transform infrared microspectroscopy can be used to collect infrared
spectra from microscopic regions of tissue sections. If spectra are collected
along a grid pattern, then maps of chemical functional groups can be produced and
correlated to tissue histopathology. In the present study, white matter from
multiple sclerosis and control brains were examined. Mapping experiments were
designed such that 17 spectra were collected at 200 microm intervals along a line
that was partially or wholly within a multiple sclerosis lesion site or within a
representative white matter region of control tissue. Data analysis was based on
earlier in vitro studies which found that the carbonyl at 1740 cm(-1) increases
when lipids become oxidized (Free Rad. Biol. Med. 16:591-601, 1994), and the
amide I peak at approximately 1660 cm(-1) broadens when proteins become oxidized
(FEBS Let. 362:165-170, 1995). The results indicated that the C=O to CH2 ratio
(1740 cm(-1):1468 cm(-1)) was elevated at several collection points in lesion
sites from multiple sclerosis brains compared to values from white matter of
control brains. Inspection of the amide I peak at 1657 cm(-1) revealed that it
was broadened towards 1652 cm(-1) in multiple sclerosis tissues but not control
tissues. These results suggest that lipids and proteins could be oxidized at
active multiple sclerosis lesion sites. The localization of these products to
lesion sites supports a role for free radicals in the pathogenesis of multiple
sclerosis.
PMID- 9655521
TI - Effect of bile acids on lipid peroxidation: the role of iron.
AB - The toxic effect of hydrophobic bile acids is claimed to be in part mediated by
lipid peroxidation. Conversely, antioxidant properties of tauroursodeoxycholic
acid (TUDC), a hydrophilic bile acid, have been suggested as a possible mechanism
by which TUDC confers its beneficial effect in a variety of diseases. We have
investigated the effect of taurodeoxycholic acid (TDC), a hydrophobic bile acid
and TUDC on lipid peroxidation using a pure lipid system both in the presence and
absence of iron ions. Neither TDC nor TUDC showed any effect on spontaneous lipid
peroxidation of phosphatidylcholine liposomes or sodium arachidonate solution.
This lack of effect excludes the possibility of direct prooxidant or antioxidant
properties for TDC and TUDC. Addition of ferrous ions (0.1 mM) to the lipid
system brought about a linear increase in lipid peroxidation with time. The
presence of TDC caused an increase in the rate and extent of iron-stimulated
lipid peroxidation. The propensity of bile acids to increase iron-induced lipid
peroxidation was related to hydrophobicity of the individual bile acids, with the
highest effect observed with taurolithocholic acid, whereas TUDC did not have any
influence. The TDC-induced increase in the iron-stimulated lipid peroxidation was
concentration dependent. Addition of TUDC (10 mM) completely abolished the effect
of TDC (2 mM) on iron-induced lipid peroxidation. This finding suggests that TUDC
does not function as an antioxidant per se but may prevent lipid peroxidation
caused by TDC. In conclusion, only in the presence of iron ions, hydrophobic bile
acids may enhance lipid peroxidation. TUDC has no antioxidant activity per se but
may counter the TDC-induced increase in iron-stimulated lipid peroxidation.
PMID- 9655522
TI - TNF-induced mitochondrial changes and activation of apoptotic proteases are
inhibited by A20.
AB - A20 zinc finger protein is a product of a cytokine-induced primary response gene.
It functions as a negative regulator of the tumor necrosis factor (TNF)
inhibiting both TNF-mediated apoptosis and activation of transcription factors.
We demonstrated that A20 overexpression blocks early TNF-induced signaling events
including the generation of free radicals, the fall in mitochondrial
transmembrane potential (delta psi(m)), and the activation of caspase-3-like
apoptotic proteases. General inhibitor of caspases, cow pox virus-derived CrmA,
also inhibited TNF-induced mitochondrial changes indicating that early caspase
activation occurs upstream from mitochondrial changes. Interestingly, changes in
mitochondrial function or induction of caspase-3-like activity induced by anti
Fas or doxorubicin were not inhibited by A20. The data show that A20 is a
specific inhibitor of TNF signaling and acts upstream of INF-induced free radical
formation, fall in mitochondrial transmembrane potential (delta psi(m)), and
activation of caspase-3-like proteases.
PMID- 9655523
TI - Does beta-carotene protect membrane lipids from nitrogen dioxide?
AB - Lipid peroxidation in rat liver microsomes, induced by nitrogen dioxide (NO2), a
free radical toxin, was examined in the absence and in the presence of varying
concentrations of beta-carotene. The extent of peroxidation was assayed by
determining the malonaldehyde formed as thiobarbituric acid reactive substances
(TBARS). When the concentration of beta-carotene was 13.8 and 43.1 nmol/mg
protein, no protection was seen, rather an increase of 10% and 30%, respectively,
in TBARS was observed as compared with the normal microsomes containing no beta
carotene. However, at beta-carotene concentrations of 66.5 and 89.4 nmol/mg
protein, only a marginal increase of 9% and 4% in TBARS, respectively, was
observed. The amount of beta-carotene consumed during peroxidation, determined by
following the absorbance at 450 nm, was found to increase linearly with increased
exposure to NO2. The direct reaction of NO2 with beta-carotene was studied in an
inert organic solvent, acetonitrile, by following the absorption spectrum of beta
carotene in the wavelength region 220-600 nm. The rate of loss of beta-carotene
was found to be much faster than that in microsomes. The results suggest that in
in vitro systems, the reaction of secondary lipid-derived radicals with beta
carotene and their relative competition for NO2 plays an important role in the
actual function of beta-carotene as a prooxidant or an antioxidant. Another lipid
soluble antioxidant, alpha-tocopherol (vitamin-E), showed significant protection
against NO2-induced lipid peroxidation at a concentration of 45 nmol/mg protein
under these conditions.
PMID- 9655524
TI - Preparation and EPR studies of lithium phthalocyanine radical as an oxymetric
probe.
AB - The electron paramagnetic resonance (EPR) spectrum of the paramagnetic center in
solid lithium phthalocyanine, LiPc, exhibits a pO2 (partial pressure of oxygen)
dependent line width. The compound is insoluble in water and is not easily
biodegradable and, therefore, is a useful spin probe for quantitative in vivo
oxymetry. Because EPR spectrometry is potentially a useful technique to
quantitatively obtain in vivo tissue pO2, such probes can be used to obtain
physiological information. In this paper, a simple experimental procedure for the
preparation of LiPc using potentiostatic electrochemical methods is described.
The setup was relatively inexpensive and easy to implement. A constant potential
ranging from 0.05 to 0.75 V versus Ag+/AgCl(s) was used for obtaining LiPc. The
EPR spectral studies were carried out using spectrometers operating at X-band and
at radiofrequency (RF) at different pO2 values to characterize the spectral
response of these crystals. The results indicate that, depending on the
electrolysis conditions, the products contain mixtures of crystals exhibiting pO2
sensitive and pO2-insensitive line widths. Electrolysis conditions are reported
whereby the pO2-sensitive LiPc crystals were the predominant product. The
influence of the working surface of the electrode and the electrolysis time on
the yield were also evaluated. The crystals of LiPc were also studied using a
time-domain RF EPR spectrometer. In time-domain EPR, the signals that survive
beyond the spectrometer dead time are mainly the narrow lines corresponding to
the pO2-sensitive crystals, whereas the signals arising from the pO2-insensitive
component of LiPc were found not to survive beyond the spectrometer dead time.
This signal survival makes the time-domain EPR method more sensitive for pO2
measurements using LiPc because the line width becomes very narrow at very low
pO2 and, concomitantly, the relaxation time T2 longer, with no modulation or
power saturation artifacts that are encountered as in the continuous wave (cw)
mode. Further, minimal contributions from object motion in the spectral data
obtained using time-domain methods make it an advantage for in vivo applications.
PMID- 9655525
TI - Oxidative damage in tissues of rats exposed to cigarette smoke.
AB - Cigarette smoke is known to contain high concentrations of free radicals and
oxidants. To examine the oxidative effect of cigarette smoking, we subjected rats
to inhalation of cigarette smoke, and measured cellular free glutathione, the
degree of protein S-thiolation, and 8-oxo-2'-deoxyguanosine (oxo8dG) in DNA.
Inhalation of the cigarette smoke for 30 days, three times a day, resulted in a
significant decrease of the total free glutathione contents in tissues,
especially in the lung. Elevated levels of oxidized glutathione and protein S
thiolation were observed in the lung but not in other tissues. Increased contents
of oxo8dG in DNA were found in all tissues analyzed. When rats were treated with
buthionine sulfoximine (BSO, 80 mg/kg/day) to deplete glutathione, the oxidative
effect of cigarette smoking was greatly potentiated. The effect of glutathione
depletion was most evident in the lung. Cigarette smoking for only 7 days
resulted in extreme depletion of the glutathione both in the lungs and in the
liver of BSO-treated rats. Furthermore, oxo8dG in DNA increased markedly,
especially in lung. The results verified that the lung is a primary target of
cigarette smoke-induced oxidative damage, and cigarette smoke exerts its
oxidative effects on the rest of the entire organs eventually. Our results
indicate that glutathione plays crucial roles in protecting proteins and DNA from
oxidation caused by cigarette smoking.
PMID- 9655526
TI - Prevention of reoxygenation injury by sodium salicylate in isolated-perfused rat
liver.
AB - Sodium salicylate can be used as a chemical trap for hydroxyl radicals, the most
damaging reactive oxygen species. Because reactive oxygen species are involved in
the pathogenesis of hepatic hypoxia/reoxygenation injury, the goal of this study
was to determine if trapping hydroxyl radicals with salicylate would prevent or
at least ameliorate such injury. Isolated rat livers, continuously perfused with
Krebs-Henseleit bicarbonate buffer in the presence or absence of salicylate (2
mM), were exposed, after 30 min of recovery, to 60 min of hypoxia, followed by 30
min of reoxygenation. During reoxygenation, control livers experienced a sharp
increase in the rate of lactic dehydrogenase release, taken as index of cell
injury, protein carbonyl content, and malondialdehyde, taken as index of protein
oxidation and lipid peroxidation, respectively. The presence of salicylate in the
solution perfusion significantly reduced the rate of lactic dehydrogenase
release, protein carbonyl content, and malondialdehyde production during
reoxygenation. Hepatic histology documented a significantly reduced cell injury
in salicylate-perfused livers compared to control livers. These data suggest that
the hydroxyl radical chemical trap sodium salicylate, acting as an antioxidant,
may represents an effective agent to reduce liver injury due to
hypoxia/reoxygenation in a model of isolated-perfused rat liver.
PMID- 9655527
TI - Reactive oxygen species and DNA oxidation in fetal rat tissues.
AB - It is well recognized that reactive oxygen species (ROS) are formed during the
reperfusion of ischemic tissues and ROS may be pathogenic in adult tissues.
Although there is little information on the formation and toxicity of ROS during
prenatal life, a strong association has been made between limb and possibly brain
malformations and uteroplacental ischemia during fetal stages of gestation. It
has been proposed that these malformations result from attack by ROS formed
during the resumption of placental perfusion. Studies reported here examined
formation of ROS in teratogenically sensitive limb and brain and insensitive
heart before and during the period of teratogenic sensitivity. Also examined was
the formation of ROS following hypoxia and reoxygenation in fetal culture and DNA
hydroxylation in sensitive and insensitive fetal tissues during uteroplacental
ischemia and reperfusion in vivo. Rates of formation of superoxide anion radical
and hydrogen peroxide declined with increasing gestational age whereas those for
hydroxyl radical increased. Hydrogen peroxide generation was greatest in
insensitive heart whereas hydroxyl radical formation was significantly lower in
brain than in limb or heart, which had comparable rates. Hydrogen peroxide
generation, which declined significantly in fetuses, but not in membranes with
gestation, failed to respond to reoxygenation in vitro. Finally, there were
significant increases in DNA hydroxylation in fetal hearts and limbs, but not in
brains during uteroplacental ischemia but no further significant change could be
detected after reperfusion.
PMID- 9655528
TI - Impairment of the mitochondrial electron chain transport prevents NF-kappa B
activation by hydrogen peroxide.
AB - A large body of work has been devoted to mechanisms leading to the activation of
the transcription factor NF-kappa B in various cell types. Several studies have
indicated that NF-kappa B activation by numerous stimuli depends on the
intracellular generation of reactive oxygen species (ROS). In this report, we
first demonstrated that inhibition of the electron transport chain by either
rotenone or antimycine A gave rise to dose-dependent inhibition of NF-kappa B
translocation induced by 150 microM of hydrogen peroxide (H2O2). Conversely, the
impairment of the mitochondrial respiratory chain did not affect T lymphocyte
treatment by TNF-alpha (tumor necrosis factor alpha) or pre-B lymphocyte
treatment with LPS (lipopolysaccharide). We also showed that oligomycine which
inhibits ATP synthase and FCCP, which uncouples respiration also led to dose
dependent inhibition of NF-kappa B activation by H2O2. All these inhibitors were
also shown to inhibit mitochondrial respiration in lymphocytes assessed by oxygen
consumption. Although only a transient drop in ATP concentration was observed
when lymphocytes were treated by H2O2, this effect was remarkably reinforced in
the presence of oligomycine demonstrating the crucial role of ATP in the signal
transduction pathway induced by H2O2.
PMID- 9655529
TI - Structure-property relationships of trimetazidine derivatives and model compounds
as potential antioxidants.
AB - Twenty-five compounds (trimetazidine derivatives and other compounds, mostly
having a free phenolic group) were examined for their radical scavenging and
antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl)
as a measure of radical scavenging capacity was assessed by two parameters,
namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z,
a kinetic parameter proposed here and derived from initial second-order rate
constants and antioxidant/DPPH ratios. Antioxidant activities were determined by
the inhibition of lipid peroxidation and albumin oxidation. The most active
compounds were derivatives having a trolox or hydroquinone moiety.
Physicochemical and structural properties were determined by molecular modeling
as lipophilicity (virtual log P calculations) and H-Surf (solvent-accessible
surface of hydroxyl hydrogen) and by quantum mechanical calculations (deltaH(ox)
= oxidation enthalpy; deltaH(abs) = enthalpy of hydrogen abstraction). QSAR
models were derived to identify molecular mechanisms responsible for the
reactivity toward the DPPH radical and for the inhibition of lipid peroxidation.
A useful prediction of antioxidant capacity could be achieved from calculated
molecular properties and the kinetic parameter developed here.
PMID- 9655530
TI - Modification of enzymatic antioxidants in retinal microvascular cells by glucose
or advanced glycation end products.
AB - Oxidative stress is one possible pathogenic mechanism to explain diabetic
microangiopathy. In the present study, we determined the antioxidant enzyme
activities in bovine retinal microvessels and cultured retinal microvascular
cells: endothelial cells (BREC) and pericytes (BRP). We further investigated the
effects of high glucose and advanced glycation end products (AGE) on these enzyme
activities in BREC and BRP. Antioxidant enzyme activities in native retinal
microvessels and BREC were quite similar but differed markedly from the BRP ones.
High glucose decreased Se-GPx activity (about 20%) in BREC compared to mannitol.
High concentrations of mannitol or NaCl increased Se-GPx activity (up to 40%)
compared to control medium, suggesting that hyperosmolarity could regulate Se-GPx
in BREC. No changes in antioxidant enzyme activities were observed when BRP were
cultured with glucose or mannitol at high concentrations. AGE-BSA had no effect
on enzyme activities in BREC, whereas 20 microM AGE-BSA increased catalase (40%)
and superoxide dismutase (60%) activities in BRP. Differences in antioxidant
enzyme activities observed between BREC and BRP, cultured with high
concentrations of glucose or AGE, might help to explain their different behavior
during the pathogenesis of diabetic retinopathy, i.e., early pericyte drop-out
and late endothelial cell proliferation.
PMID- 9655531
TI - Retroviruses, ascorbate, and mutations, in the evolution of Homo sapiens.
AB - Mutations, induced by free radicals, provide a rich molecular palette that other
evolutionary forces can select for or against. A recent hypothesis proposed that
large numbers of free radicals were produced when, millions of years ago,
Anthropoidea lost the ability to produce endogenous ascorbate, increasing the
frequency of mutations and accelerating the evolution of higher primates.
Recognizing that retroviruses have been active throughout the period of primate
evolution, we suggest that an endogenous retrovirus or other retroviral-like
element may have been involved in mutating the gene coding for gulonolactone
oxidase (GLO), the terminal step in ascorbate synthesis, approximately 45 million
years ago. This possibility is supported by the presence of Alu elements (a
common primate retroelement) adjacent to the site of a missing segment of the
nonfunctional GLO gene. Although Homo sapiens and other higher primates produce
other endogenous antioxidants, including superoxide dismutase and uric acid, they
do not quench the same radicals as ascorbate and cannot fully compensate for a
lack of endogenous ascorbate. As a consequence, a retrovirus may have played a
pivotal role in primate and H. sapiens evolution, and the absence of endogenous
ascorbate may be continuing to accelerate the rate of H. sapiens and primate
evolution.
PMID- 9655532
TI - Prospective randomized double blind placebo-controlled evaluation of azithromycin
for treatment of cat-scratch disease.
AB - OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients
with typical cat-scratch disease. DESIGN: Prospective, randomized, double blind,
placebo-controlled clinical trial. SETTING: Large military medical center and its
referring clinics. PATIENTS: Active duty military members and their dependents
with laboratory-confirmed, clinically typical cat-scratch disease. INTERVENTION:
Study participants assigned by randomization to treatment with oral azithromycin
or placebo for 5 days. OUTCOME MEASURES: Lymph node volume was calculated using
three dimensional ultrasonography at entry and at weekly intervals. The
ultrasonographer was blinded to the treatment groups. Endpoint evaluations were
predetermined as time in days to 80% resolution of the initial total lymph node
volume. RESULTS: Demographic and clinical data showed that the azithromycin and
placebo treatment groups were comparable at entry although the placebo group
tended to be older. Eighty percent decrease of initial lymph node volume was
documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo
treated controls during the first 30 days of observation (P = 0.026). After 30
days there was no significant difference in rate or degree of resolution between
the two groups. CONCLUSIONS: Treatment of patients with typical cat-scratch
disease with oral azithromycin for five days affords significant clinical benefit
as measured by total decrease in lymph node volume within the first month of
treatment.
PMID- 9655533
TI - Short course therapy with cefuroxime axetil for group A streptococcal
tonsillopharyngitis in children.
AB - BACKGROUND: Tonsillopharyngitis caused by group A beta-hemolytic streptococci
(GABHS) is common in pediatric clinical practice. Standard penicillin therapy may
be associated with poor compliance, penicillin tolerance in GABHS and microbial
copathogenicity. Alternative treatments are available (e.g. oral cephalosporins),
and data suggest that shorter courses of these agents may be effective.
OBJECTIVE: This open, randomized, multicenter study compared a conventional 10
day course of the broad spectrum oral cephalosporin, cefuroxime axetil, with a
shorter 5-day course. METHODS: Cefuroxime axetil suspension, 10 mg/kg, was given
twice daily to children (ages 3 to 13 years) screened for GABHS
tonsillopharyngitis. Patients were assessed clinically and bacteriologically 4 to
7 days after completing the course and followed up at 21 to 28 days. Among 651
patients recruited 520 had throat cultures positive for GABHS and were randomized
to treatment. RESULTS: In the 406 patients with microbiologically confirmed GABHS
infection, eradication of the initial pathogen was recorded in 177 of 201 (88%)
and 189 of 205 (92%) of patients in the 5- and 10-day groups, respectively, at
posttreatment. At follow-up, 137 of 162 (85%) of patients in the 5-day group and
145 of 167 (87%) in the 10-day group maintained bacteriologic eradication. All
posttreatment isolates of GABHS were susceptible to cefuroxime, and reinfection
with a different serotype of GABHS was rare (< or =2%) in both groups. The rates
of recurrence of the pretreatment serotype were 10 and 7% in the 5- and 10-day
groups, respectively. CONCLUSIONS: Short course therapy with cefuroxime axetil
suspension may offer an effective alternative treatment to conventional regimens,
with potential for better compliance and reduced costs.
PMID- 9655534
TI - Self-reported prescribing of antibiotics for children with undifferentiated acute
respiratory tract infections with cough.
AB - BACKGROUND: Physicians are often called on to manage children with acute
respiratory tract infections with cough when the clinical presentation may not
allow a differentiation between viral and bacterial etiology. To develop
guidelines for appropriate antibiotic use, it is necessary to understand the
present prescribing patterns of physicians who manage children presenting with
such an undifferentiated acute respiratory tract infection with cough (UARTIC).
OBJECTIVES: To determine the variability of self-reported prescribing habits for
antibiotics for children with UARTIC. METHODS: In this cross-sectional survey by
a modified Dillman's Total Design Method, a mail-out questionnaire was
administered to a random sample of 181 primary care family physicians and
pediatricians (Toronto, Ontario, Canada) to assess perceptions of their own
antibiotic-prescribing habit. RESULTS: Completed questionnaires were received
from 136 (75%) eligible physicians; 32% reported that > 10% of their office
visits were for UARTIC. For a 3-day history of UARTIC 24% reported prescribing
antibiotics or antibiotics in reserve (i.e. a prescription to be filled if the
patient's condition does not improve) always or most times. This increased to 45%
when UARTIC had worsened in the 24 h before the office visit (P < 0.001).
CONCLUSION: When a pediatric patient presented with UARTIC, antibiotics or
antibiotics in reserve were prescribed in the absence of clear indicators of
bacterial infection. Research- and evidence-based guidelines are needed to
support rational antibiotic use for UARTIC.
PMID- 9655535
TI - Resistance pattern of middle ear fluid isolates in acute otitis media recently
treated with antibiotics.
AB - BACKGROUND: Little information is available about the effect of antibiotic
treatment on the prevalence and MIC of the subsequently isolated pathogens in
cases of acute otitis media (AOM) failing a course of antibiotic therapy. This
information is important, particularly regarding the effectiveness of the oral
antibiotics used in children failing initial therapy. PATIENTS AND METHODS: One
hundred eighty-one children with culture-positive AOM were prospectively studied
between October, 1995, and July, 1996. Sixty-three (35%) patients received
various antibiotics for variable periods during the 14 days preceding enrollment.
RESULTS: A total of 94 Streptococcus pneumoniae (Pnc) and 113 Haemophilus
influenzae (Hi) were isolated. Thirty-eight Pnc and 35 Hi were isolated in the 63
patients with recently treated AOM. Pnc as a single isolate was more prevalent in
patients recently treated with antibiotics (27 of 63, 43%) than among those not
recently treated (32 of 118, 27%, P = 0.047). The MIC50 values of penicillin,
cefaclor and cefuroxime axetil for Pnc were significantly higher in the
pneumococci isolated from patients recently treated than among those isolated
from patients not recently treated with antibiotics (0.38, 3 and 0.75 microg/ml
vs. 0.094, 0.38 and 0.12 microg/ml, respectively). Seventy-nine percent of Pnc
isolates in the recently treated group had MIC for penicillin of >0.1 microg/ml
vs. only 47% in those not recently treated (P < 0.05). The respective figures for
MIC >0.5 microg/ml of cefaclor were 79% vs. 41% for the recently treated and not
recently treated groups (P < 0.001); cefuroxime MIC >0.5 microg/ml was found in
61 and 25%, respectively (P = 0.001). CONCLUSIONS: Pneumococcus is more prevalent
in AOM after a recent antibiotic treatment, and the MIC of the commonly used beta
lactam drugs for Pnc is considerably higher in this setting. In view of our data,
the use of oral cephalosporins like cefaclor or cefuroxime as second line drugs
in the treatment of unresponsive AOM, particularly in regions where resistant PNC
is prevalent, should be reconsidered.
PMID- 9655536
TI - Erythromycin resistance of Streptococcus pyogenes in Madrid.
AB - BACKGROUND: Erythromycin is considered to be an adequate alternative to
penicillin for patients who are allergic to penicillin. Erythromycin-resistant
Streptococcus pyogenes strains have been reported in some parts of the world.
METHOD: The in vitro activity of erythromycin and other antimicrobial agents was
determined in a total of 1310 clinical Streptococcus pyogenes isolates collected
in the city of Madrid from January, 1993, through December, 1996. RESULTS: All
strains showed susceptibility to penicillin, rifampin, vancomycin and
chloramphenicol. Tetracycline resistance was 8.5%. In 36 of the strains (2.7%)
MIC was 4 microg/ml for ofloxacin. Clindamycin resistance was observed in only 18
strains (1.4%); this resistance was constitutive in 15 and inducible in 3
strains. Resistance to erythromycin was observed in 14.3% of the strains, showing
an increase during the study period (2.0% in 1993 vs. 22.4% in 1996; chi square
for linear trend 68.8, P < 0,0001); >90% of them showed the novel resistance
phenotype described by Seppala et al. and 32 of 32 of these strains showed by PCR
the 1.4-kb fragment of the mefA gene recently described as the novel macrolide
efflux resistance determinant. The erythromycin-resistant strains were isolated
more often in pediatric patients (144 of 872) than in adults (44 of 438) (chi
square 9.9, P = 0.0016). CONCLUSION: The study emphasizes the need to screen for
resistance to macrolides in S. pyogenes and indicates that resistance to
erythromycin in S. pyogenes has increased significantly in Madrid.
PMID- 9655537
TI - Chlamydia pneumoniae in children attending day-care centers in Gavle, Sweden.
AB - BACKGROUND: The epidemiology of Chlamydia pneumoniae in healthy children has not
been established. METHODS: This investigation used polymerase chain reaction
(PCR) to study the epidemiology of C. pneumoniae in presumed healthy children.
Four hundred fifty-three children and 142 personnel at 9 day-care centers were
investigated for carriage of C. pneumoniae. Children found to be positive by PCR
were also investigated with serology, and their family members were tested with
PCR. RESULTS: One hundred and three (22.7%) children had a positive PCR, as had
33 (23.2%) personnel. Fourteen percent of the children younger than 3 years had a
positive PCR test compared with 26% of the older children (P < 0.01). No
correlation was found between respiratory symptoms and carriage of C. pneumoniae.
Mothers were more often positive in the PCR test as compared with fathers
(relative risk, 2.59; 95% confidence interval, 1.16 to 5.78). Antibodies to C.
pneumoniae were found in 27 of 97 PCR-positive children; only 2 of whom were
younger than 3 years. CONCLUSION: C. pneumoniae can be commonly found in young
children attending day care. Most of the youngest children did not develop
specific antibodies. Children may have subclinical infections with C. pneumoniae.
The organism seems to be easily communicable among individuals living in close
proximity.
PMID- 9655538
TI - Cerebrospinal fluid profile in patients with acute Kawasaki disease.
AB - BACKGROUND: Kawasaki disease (KD) is an acute vasculitis of infancy and early
childhood for which there is currently no diagnostic test. The clinical
presentation of KD may initially resemble other infectious diseases, including
bacterial or viral meningitis. For this reason lumbar puncture (LP) is sometimes
performed during the evaluation of these patients. To understand the range of
cerebrospinal fluid (CSF) changes that may be associated with acute KD, a
retrospective review of unselected KD patients from three pediatric centers was
performed. METHODS: Retrospective chart review was performed on KD patients
evaluated during the first 10 days of illness who had an LP performed before the
administration of intravenous gamma-globulin. RESULTS: During the 6.5-year study
period, 46 KD patients underwent LP as part of their clinical evaluation. Of
these patients 18 (39.1%) had CSF pleocytosis, 1 (2.2%) had a CSF glucose <45
mg/dl and 8 (17.4%) had an elevated CSF protein. Of the patients with CSF
pleocytosis, the median white blood cell count was 22.5 cells (range, 7 to 320
cells), with a median of 6.0% neutrophils (range, 0 to 79%) and 91.5% mononuclear
cells (range, 11 to 100%). CONCLUSIONS: In the present series approximately one
third of KD patients who underwent an LP had CSF pleocytosis with a mononuclear
cell predominance. No patient had significant hypoglycorrhachia, and elevation of
the CSF protein was uncommon. CSF abnormalities were similar between US and
Japanese KD patients. The basis for the CSF pleocytosis in acute KD patients
remains unknown.
PMID- 9655539
TI - Prevalence of intestinal infections caused by diarrheagenic Escherichia coli in
Bedouin infants and young children in Southern Israel.
AB - OBJECTIVE: To evaluate the prevalence of different Escherichia coli categories in
symptomatic and asymptomatic infants and children residing in a Bedouin township
in Southern Israel. METHODS: A total of 1613 stool samples were collected from a
cohort of 234 infants and young children followed from birth up to 2 years of
age. E. coli colonies from stool cultures from children during a diarrhea episode
and those from nondiarrhea stools were hybridized with DNA probes specific for
enteropathogenic, enteroinvasive, enterotoxigenic (ETEC), enteroaggregative,
diffuse adherent and enterohemorrhagic strains. RESULTS: There were 1469 of 1613
(91%) samples positive for E. coli. The prevalence of E. coli categories was:
enteroaggregative (25.9%); diffuse adherent (21.8%), ETEC (12.9%);
enteropathogenic (7.3%); enterohemorrhagic (0.5%); and enteroinvasive (0.2%).
ETEC, expressing the heat-stable enterotoxin (ST), was the only category isolated
significantly more often from cases than from controls (P = 0.005). Of the two
heat-stable enterotoxins screened in this study, only ETEC-heat stable
enterotoxin (STh), the form isolated from human pathogenic ETEC, could be
associated with diarrhea, whereas ETEC-STp, produced by ETEC of porcine origin,
was not related to diarrhea. ETEC infections peaked during the warm, dry season.
Prolonged shedding of E. coli postdiarrhea was not found in this population.
CONCLUSION: The present cohort study confirmed that in this semiurban area,
highly endemic for diarrheal disease, ETEC is an important cause of diarrhea in
children.
PMID- 9655540
TI - Serologic and virologic evidence for frequent intrauterine transmission of human
parvovirus B19 with a primary maternal infection during pregnancy.
AB - OBJECTIVE: To define the intrauterine viral transmission rate during primary
maternal parvovirus B19 infection and identify factors that may influence this
rate. METHODS: Forty-three pregnant women at two medical centers were identified
with a primary B19 infection and followed to delivery. At delivery maternal and
infant (umbilical cord) blood was obtained for B19 serologic and virologic PCR
testing. RESULTS: All of the women delivered healthy infants at term and none was
hydropic. Overall 22 (51%) of the 43 infants had some evidence of a congenital
B19 infection. B19-specific IgM was detected in 11 infants at delivery, B19 IgA
was detected in 10 and B19 DNA was detectable by PCR in 11 infants. One infant
was negative at birth but became positive for IgM, IgA and PCR at 6 weeks of age.
No association was found between the likelihood of intrauterine infection and:
maternal age; symptomatic maternal infection; method of delivery; maternal IgG
titer at delivery; maternal IgG avidity at delivery; or maternal viremia at
delivery. Intrauterine infection was associated with maternal IgM positivity at
delivery; this association may have been a result of maternal infection occurring
later in gestation. CONCLUSION: Although the incidence of intrauterine hydrops
and fetal demise after maternal infection is low, there is a high rate of
intrauterine viral infection that occurs throughout gestation and yields newborns
who, although infected in utero, are asymptomatic at birth.
PMID- 9655541
TI - Comparison of two antiretroviral triple combinations including the protease
inhibitor indinavir in children infected with human immunodeficiency virus.
AB - OBJECTIVE: The effects of two antiretroviral triple combinations including the
protease inhibitor indinavir on the surrogate markers, viral load and CD4 cells
were evaluated. METHODS: Fifteen patients with high viral load or disease
progression under their prior antiretroviral therapy were switched to
zidovudine/lamivudine/indinavir (Group A, n = 10) or
stavudine/lamivudine/indinavir (Group B, n = 5). Serial determinations of viral
load and CD4 cells were performed. RESULTS: The median reduction of the viral
load was 0.6 log after 3 months and 0.8 log after 6 months in Group A and 2.5 and
2.4 log after 3 and 6 months in Group B, respectively. After 3 and 6 months 3 of
10 patients in Group A and 3 of 5 patients in Group B had viral load reductions
below the detection limit of the assay. Patients with an additional switch of
nucleoside analogues at start of indinavir therapy (regardless of the specific
reverse transcriptase inhibitor used) had significantly better reductions of the
viral load than patients without such a switch (median 2.3 log vs. 0.2 log after
6 months, P < 0.05). In Group A the median of the relative increase of CD4 cells
was 37% after 3 months and 57% after 6 months (P = 0.002); in Group B the medians
of the relative increase of CD4 cells were 145 and 163% (not significant),
respectively. Two patients from Group A and 1 from Group B developed renal
calculi, which resolved after adequate hydration. One patient was withdrawn
because of intractable vomiting attributed to indinavir. CONCLUSION: In a small
cohort of HIV-infected pediatric patients with extensive prior antiretroviral
treatment, triple therapy including indinavir had a sustained effect on the
decrease of the viral load and the increase of CD4 cells similar to results
obtained in antiretrovirally experienced adults. This effect was significantly
better in patients with an additional switch of a nucleoside analogue at start of
triple therapy with indinavir than in patients without such a change.
PMID- 9655542
TI - Maternal carriage of group B streptococci in developing countries.
AB - BACKGROUND: Group B streptococcus (GBS) is a leading cause of neonatal sepsis in
many industrialized countries, but reports from the developing world infrequently
identify this pathogen among newborns with sepsis. Studies of GBS colonization
among women living in developing countries were reviewed to determine whether
lower colonization rates might account for these findings. METHODS: Literature
was reviewed with the use of Medline Express (1980 to 1996) and Abstracts on
Tropical Agriculture and Rural Development in the Tropics (1975 to 1995). The
methods of each report were considered adequate if specimens were collected from
the vagina and if selective broth media were used. RESULTS: Thirty-four studies
reported results of cultures from 7730 women; overall colonization was 12.7%.
Among only those studies in which methods were adequate, 17.8% (675 of 3801)
women were identified as colonized. Studies with adequate methods found
significantly higher colonization rates (relative risk, 2.3; 95% confidence
interval, 2.0 to 2.6) than those using inadequate methods. When analysis was
restricted to reports with adequate methods, the prevalence of colonization by
region was as follows: Middle East/North Africa, 22%; Asia/Pacific, 19%; Sub
Saharan Africa, 19%; India/Pakistan, 12%; and Americas, 14%. CONCLUSION: Although
there is significant geographic variation in the proportion of women colonized
with GBS, the range of colonization reported from developing countries is similar
to that identified in populations studied in the United States. Specimen
collection and microbiologic methods are important factors in identification of
women colonized with GBS.
PMID- 9655543
TI - Candidemia in a neonatal intensive care unit: trends during fifteen years and
clinical features of 111 cases.
AB - OBJECTIVE: To determine changes in the incidence of candidemia in a neonatal
intensive care unit (NICU) during a 15-year period (1981 to 1995) and to compare
the prevalence and case fatality rates of Candida albicans and Candida
parapsilosis infections. METHODS: A retrospective study was conducted of
candidemia occurring in infants in a NICU between January 1, 1981, and December
31, 1995. Cases were identified through computerized searching of a microbiology
blood culture database. Candidemia was considered contributory to mortality if
death occurred within 3 days of positive blood cultures or if there was autopsy
evidence of disseminated candidiasis. RESULTS: One hundred eleven cases of
candidemia occurred in 107 infants, representing 1% of all NICU patients during
the study period. The rate of candidemia in the NICU increased from 2.5 cases per
1000 admissions in 1981 to 1985, to 4.6 per 1000 admissions in 1986 to 1990 and
to 28.5 per 1000 in 1991 to 1995 (P = 0.001). C. albicans was the predominant
cause of candidemia between 1981 and 1990. C. parapsilosis was the most prevalent
species between 1991 and 1995, causing 53 of 89 cases (60%). The mortality from
C. albicans, 13 of 50 cases (26%), was significantly higher than the mortality
from C. parapsilosis, 2 of 54 (4%) (P = 0.002; relative risk, 7; 95% confidence
interval, 1.7 to 30). CONCLUSIONS: The rate of candidemia in our neonatal
intensive care unit increased >11-fold in the 15 years from 1981 to 1995; the
prevalent Candida species shifted from C. albicans to C. parapsilosis; and
candidemia associated with C. albicans has significantly higher mortality than
with C. parapsilosis.
PMID- 9655544
TI - Multiresistant Pseudomonas aeruginosa outbreak in a pediatric oncology ward
related to bath toys.
AB - BACKGROUND: Nosocomial outbreaks of Pseudomonas aeruginosa in pediatric hospitals
frequently involve neonates and immunosuppressed patients and can cause
significant morbidity and mortality. OBJECTIVE: To describe the investigation of
a multidrug-resistant P. aeruginosa outbreak in a pediatric oncology ward at the
Royal Children's Hospital, Melbourne, Australia. DESIGN AND METHODS: Specimens
were collected from infected patients and the ward environment. Bacterial
isolates were characterized by antibiotic susceptibility patterns and bacterial
DNA fingerprinting performed by pulsed-field gel electrophoresis (PFGE). A case
control study was carried out to assess possible risk factors for infection.
RESULTS: Eight patients had clinical illnesses including bacteremia (n = 5) and
infections of skin (n = 2), central venous catheter site (n = 1) and urinary
tract (n = 1). The environmental ward survey yielded isolates of multiresistant
P. aeruginosa from a toy box containing water-retaining bath toys, as well as
from three of these toys. Pulsed-field gel electrophoresis of bacterial DNA
demonstrated identical band patterns of the isolates from patients, toys and toy
box water. A case-control study involving the 8 cases and 24 disease-matched
controls demonstrated a significant association between P. aeruginosa infection
and use of bath toys (P = 0.004), use of bubble bath (P = 0.014), duration of
stay (P = 0.007) and previous antibiotic exposure (P = 0.026). Cultures from the
bubble bath liquid were negative. CONCLUSION: This is the first description of a
nosocomial outbreak associated with toys. We caution against the use of water
retaining bath toys in wards treating immunocompromised children.
PMID- 9655545
TI - Combination antiretroviral therapy.
PMID- 9655546
TI - Clarithromycin and azithromycin.
PMID- 9655547
TI - Infectious diseases in internationally adopted children: the past five years.
PMID- 9655549
TI - Comparison of oral erythromycin, local administration of streptomycin and placebo
therapy for nonsuppurative Bacillus Calmette-Guerin lymphadenitis.
PMID- 9655548
TI - Central nervous system tuberculosis after resolution of miliary tuberculosis.
PMID- 9655550
TI - Relationship between unsupplemented vitamin A serum concentrations and measles
vaccine response in Jamaican children.
PMID- 9655551
TI - Primary human immunodeficiency virus type 1 infection during pregnancy associated
with transmission of SI/MT-2 cell tropic virus and precipitous loss of CD4 cells
in mother and infant.
PMID- 9655552
TI - Streptococcus pneumoniae-associated hemolytic uremic syndrome.
PMID- 9655553
TI - Infection control for neonatal gram-negative bacterial infections.
PMID- 9655554
TI - Swabbing computers in search of nosocomial bacteria.
PMID- 9655555
TI - Raw beef consumption and improper use of chopsticks as a possible cause of
Escherichia coli O157 infection in Japan.
PMID- 9655557
TI - Otoscopy for the diagnosis of otitis media.
PMID- 9655558
TI - Use of tympanometry in office practice for diagnosis of otitis media.
PMID- 9655559
TI - Acoustic reflectometry: spectral gradient analysis for improved detection of
middle ear effusion in children.
PMID- 9655560
TI - Comparison of spectral gradient acoustic reflectometry and other diagnostic
techniques for detection of middle ear effusion in children with middle ear
disease.
PMID- 9655561
TI - Spectral gradient acoustic reflectometry for the detection of middle ear effusion
by pediatricians and parents.
PMID- 9655562
TI - Implications of pharmacokinetics in making choices for the management of acute
otitis media.
PMID- 9655563
TI - Protecting the therapeutic advantage of antimicrobial agents used for otitis
media.
PMID- 9655564
TI - Treatment of acute otitis media in an era of increasing microbial resistance.
PMID- 9655565
TI - Current recommendations for initial therapy in hypertension: are they still
valid? Introduction.
AB - This symposium will address questions regarding current recommendations for
initial therapy in the management of hypertension: Are we treating too many
hypertensive patients or too few? When do we start treatment with medications and
what medications should we use? Professor Lawrence Ramsay from England will
discuss the concept of absolute versus relative risk and review the long-term
hypertension treatment trials and what they have and have not told us. Dr.
Michael Weber of New York will discuss some newer data on angiotensin converting
enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel
blockers and attempt to answer the question: are these data sufficient to warrant
recommending these agents as initial therapy? Finally, Dr. Henry Black of Chicago
and I will update a new-old concept: is it time to consider low-dose fixed
combination therapy as initial treatment in hypertension?
PMID- 9655566
TI - The role of combination therapy in the treatment of hypertension.
AB - Only approximately 40% to 50% of hypertensive patients will achieve goal blood
pressures of <140/ 90 mm Hg with monotherapy, regardless of the medication used.
Fixed-dose combination therapy with two different classes of antihypertensive
agents will achieve goal pressures in more than 70%. The sixth Joint National
Committee on Detection, Evaluation, and Treatment of High Blood Pressure has
suggested that the use of combination therapy is appropriate as initial
treatment. The advantages of combinations include: 1) greater blood pressure
decrease and response rates than monotherapy; 2) fewer side effects with small
doses of two drugs than with large doses of one agent; 3) improved adherence to
treatment; and 4) possibly lower cost of therapy. Many different combinations of
diuretics and beta-blockers, angiotensin converting enzyme (ACE) inhibitors and
angiotensin II receptor antagonists, as well as ACE inhibitors and calcium
antagonists are available. Two of these, Ziac and Capozide, have been approved as
initial therapy. It is possible that the number of hypertensive individuals
controlled at goal blood pressure levels will be increased if combination therapy
is used as initial treatment.
PMID- 9655567
TI - The rationale for differing national recommendations for the treatment of
hypertension.
AB - This article examines the rationale for the differences in the guidelines for
hypertension management of four national or international bodies: the Joint
National Committee (JNC-V), The World Health Organization/International Society
of Hypertension (WHO-ISH), the British Hypertension Society (BHS), and the New
Zealand guidelines. These guidelines agree on many aspects of management, but
differ on two very important points-the drugs of first choice for hypertension,
and the indications for drug treatment of uncomplicated mild hypertension. JNC-V
recommends treatment routinely of all people with a sustained blood pressure of
140/90 mm Hg, whereas the BHS guidelines advise treatment routinely at 160/100 mm
Hg. Such differences in the threshold for treatment have a major impact on the
proportion of the adult population to be treated, and on the benefit from
treatment. JNC-V was heavily influenced by the Hypertension Detection and Follow
up Program (HDFP), which appeared to show a large benefit from the treatment of
uncomplicated mild hypertension, whereas the BHS guidelines were influenced by
the Medical Research Council (MRC) Trial, which showed a very small benefit.
However, the apparent differences in absolute benefit between these, and other,
randomized controlled trials is related entirely to differences in the absolute
cardiovascular risk of the populations studied. In populations and in individual
patients the benefit from antihypertensive treatment is determined by the
absolute cardiovascular risk. Blood pressure by itself is a very weak predictor
of risk or benefit from treatment. In uncomplicated mild hypertension the need
for drug therapy should be based on the absolute risk of cardiovascular
complications, estimated by considering age, sex, serum cholesterol level,
diabetes mellitus status, and smoking habits, in addition to blood pressure.
Doctors cannot estimate absolute risk accurately informally or intuitively, and
the next generation of guidelines should incorporate a simple but accurate method
for estimating cardiovascular risk, similar to that in the New Zealand
guidelines. The decision to treat, or not treat, uncomplicated mild hypertension
should be based on a formal estimate of absolute cardiovascular risk and not on
an arbitrary blood pressure threshold. As regards drugs of first choice, the
available evidence supports strongly the stance of JNC-V and JNC VI that
diuretics and beta-blockers should be preferred unless they are contraindicated,
or unless there are positive indications for other drug classes.
PMID- 9655568
TI - Translating data on antihypertensive drugs into clinical practice.
AB - Two problems in the treatment of hypertension continue to be largely unsolved.
The first, and more simple, is our inability to adequately control blood pressure
in the majority of hypertensive patients. This not only reflects the difficulty
of retaining patients in effective treatment programs, but also of convincing
physicians to strive for optimal blood pressure levels. There is a continuing
need for new antihypertensive drugs and combinations to help accomplish these
goals. The second major problem is that the major clinical endpoints, including
coronary events and renal failure, have not been adequately reduced by
traditional therapies. Standard regimens, particularly those including diuretics,
have protected against strokes and heart failure. Our improved understanding of
vascular biology in hypertension has directed interest to the mechanisms in
hypertensive patients that might accelerate atherosclerosis and vascular events
in these individuals. This involves addressing the concomitant metabolic risk
factors that comprise the "Hypertension Syndrome," and, perhaps of equal
importance, finding therapies that directly inhibit unwanted types of growth and
proliferative activities within the walls of critical arteries. Many substances
within the endothelium and the vascular wall may participate as initiators or
mediators of pathology, but most information thus far has focused on the renin
angiotensin system. Angiotensin converting enzyme inhibitors (and potentially
angiotensin receptor blockers) have provided coronary and renal protection in
various cardiovascular conditions, though not yet in formal hypertension trials.
Calcium channel blockers have also shown promise, including recent stroke and
cardiovascular benefits in patients with isolated systolic hypertension, but,
again, definitive coronary data in hypertension are awaited. Unless concomitant
conditions mandate the selection of a particular antihypertensive drug class,
physicians currently have a dilemma: should they choose drugs from older classes
that have not provided full protection? Or, should they prescribe newer agents
with exciting potential but with, as yet, unproved endpoint benefits in
hypertension? Until currently ongoing prospective trials of antihypertensive
therapy are completed, physicians must be guided by their own interpretations of
the available data.
PMID- 9655569
TI - Reproductive performance, calf growth, and milk production of first-calf heifers
sired by seven breeds and raised on different levels of nutrition.
AB - We evaluated heifers crossbred from seven breeds of sires (Hereford, Angus,
Belgian Blue, Piedmontese, Brahman, Boran, and Tuli) and three breeds of dams
(Angus, Hereford, and MARC III [four-breed composite]). Heifers were mated to Red
Poll sires to calve at 2 yr of age. Heifers were placed in two treatments from
weaning to breeding and raised on a high nutrition level (15.8 Mcal ME/d) or on
80% of the high nutrition level (12.6 Mcal ME/d). Breeds differed in the age of
the heifers at parturition (P = .03). Birth weights of calves differed by
maternal grandsire (P < .001) but not by heifer treatment (P = .91) or maternal
grandam (P = .19). Heifers differed in their postpartum interval to estrus by
sire breed (P = .001). Calf age at weaning (P = .02), calf ADG (P < .001), and
205-d weight (P < .001) differed between breeds of maternal grandsires. Milk
production from 50 to 200 d of lactation was greatest for heifers of Belgian Blue
(1,070 +/- 30 kg) and Brahman (1,029 +/- 38 kg) sires. Milk production did not
differ with treatment group (P = .84). This study suggests that over a diverse
group of breeds, accelerated rates of gain during the postweaning period within
the ranges of this study do not result in increased production efficiency of the
cows.
PMID- 9655570
TI - Pregnancy rates of postpartum beef cows that were synchronized using Syncro-Mate
B or the Ovsynch protocol.
AB - We compared pregnancy rates of beef cows subjected to the traditional Syncro-Mate
B protocol or the new Ovsynch protocol and timed insemination. Multiparous Angus
cows (n = 436) were stratified by age, postpartum interval, and AI sire and were
randomly divided into two treatment groups for synchronization of
estrus/ovulation. Approximately half of the cows (n = 216) received the
traditional Syncro-Mate-B protocol with 48-h calf removal from the time of
implant removal until breeding. The remaining cows (n = 220) received the Ovsynch
protocol, which consists of an injection of GnRH (100 microg) on d -10, an
injection of PGF2alpha (25 mg) and 48-h calf removal on d -3, another injection
of GnRH and calf return on d -1, and timed insemination 24 h later (d 0). Blood
samples were collected from all cows before treatment to identify anestrous and
cyclic females. Pregnancy rates were higher (P < .025) for Ovsynch-treated cows
(54%) than for Syncro-Mate-B-treated cows (42%). Pregnancy rates of cyclic
Ovsynch-treated cows (59%) were higher (P < .005) than pregnancy rates of cyclic
Syncro-Mate-B-treated cows (38%). Pregnancy rates of anestrous cows also tended
to favor synchronization with the Ovsynch protocol. From these data, we conclude
that the Ovsynch protocol is capable of inducing a fertile ovulation in cyclic
and anestrous beef cows and that pregnancy rates to a timed insemination are
higher than those obtained with synchronization of estrus using Syncro-Mate-B.
PMID- 9655571
TI - Sex effects on breed of sire differences for birth, weaning, and yearling
weights.
AB - Weights of males and females can be considered to be correlated traits with
different averages and variances. This study attempted to determine whether
defining traits as expressed in males or in females would change estimates of
breed of sire differences needed to calculate across-breed factors for adjustment
of within-breed EPD to across-breed EPD. Records from the US Meat Animal Research
Center of progeny of Hereford, Angus, and MARC III composite dams mated to 12
sire breeds that had been used to calculate breed of sire adjustments in 1996
were used. Breeds of sire were Hereford, Angus, Shorthorn, Brahman, Simmental,
Limousin, Charolais, Maine-Anjou, Gelbvieh, Pinzgauer, Tarentaise, and Salers.
Female and male records for birth (BWT), weaning (WWT), and yearling (YWT)
weights were considered to be separate although correlated traits. Heritability
estimates for expression as females and males were as follows: .44 and .47 for
BWT, .25 and .19 for WWT, and .55 and .49 for YWT. Corresponding genetic
correlations between expression in males and females were .85, 1.00, and .92.
Phenotypic standard deviations were slightly larger and coefficients of variation
slightly smaller for males than for females; the largest differences were for
YWT. Breeds ranked similarly for female and male weights; the major exception was
Brahman for BWT. Averages of breed of sire contrasts for expression in females
and males were almost identical to contrasts from analyses of combined male and
female records. Largest differences between averaged and combined breed of sire
contrasts were approximately 1 kg for BWT and WWT and approximately 2 kg for YWT.
The results show that considering male and female weights as separate traits is
not needed in calculation of across-breed adjustment factors from US Meat Animal
Research Center records.
PMID- 9655572
TI - Technical note: Detection of bovine kappa-casein variants A, B, C, and E by means
of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).
AB - We used polymerase chain reaction-single strand conformation polymorphism (PCR
SSCP) analysis to screen the most frequent variants (A, B, C, and E) found in the
bovine kappa-casein gene. The PCR products (453 bp) were heat-denatured, loaded
onto nondenaturing polyacrylamide gels, and silver-stained. Each variant yielded
patterns clearly distinguishable from the others. Optimal conditions for the
simultaneous detection of the four variants were 12% polyacrylamide gels (100:1
acrylamide:bis-acrylamide ratio) with 5% glycerol and a constant running
temperature of 10 degrees C. Eight reference samples initially used for this
purpose and 40 anonymous samples of different cattle breeds diagnosed by PCR-RFLP
and PCR-SSCP showed no discrepancies between the two methods and confirmed
previous results. Because it is cost-effective, sensitive, and fast, PCR-SSCP is
strongly recommended to routinely screen kappa-casein variants for industrial
purposes or in cattle selection schemes.
PMID- 9655573
TI - Additive and nonadditive genetic variability for growth traits in the Turipana
Romosinuano-Zebu multibreed herd.
AB - Intrabreed additive genetic, environmental, and phenotypic variances and
covariances for Romosinuano (R) and Zebu (Z), as well as interbreed nonadditive
genetic variances and covariances (sire x breed-group-of-dam interactions), for
birth weight (BWT), weaning weight (WW), and postweaning gain (GW) were computed
using a Romosinuano-Zebu multibreed data set from the Turipana Experiment Station
in Colombia. Covariances were estimated with a sire-maternal grandsire model,
using a multibreed REML procedure. The computing algorithm was a generalized
expectation-maximization (GEM) algorithm. This algorithm yields no asymptotic
standard errors as part of its computations. Because of the small size of the
data set (2,546 calves), these REML covariance estimates should be viewed with
caution. Estimates of intrabreed heritabilities were similar to the ratios of
interbreed nonadditive to phenotypic variances (interactibilities) for direct and
maternal effects of the growth traits evaluated in this study. Intrabreed
heritability estimates for BWT, WW, and GW direct genetic effects were .16, .09,
and .14, for R and .24, .10, and .14 for Z. Corresponding heritability values for
maternal effects were .18, .09, and .23 for R and .14, .13, and .07 for Z.
Interactibility estimates were .21, .05, and .12, for direct and .26, .04, and
.11, for maternal BWT, WW, and GW. Negative correlations between additive
maternal weaning weight and direct and maternal postweaning gain, as well as
between environmental weaning weight and postweaning gain, suggested that there
was compensatory postweaning gain in this herd. Estimates of genetic variation
and predictions of expected progeny differences showed that Romosinuano animals
competed well against Zebu and RZ crossbred animals under the tropical
environmental conditions at Turipana.
PMID- 9655574
TI - Survival, body weights, feed efficiency, and carcass traits of 7/8 White
Composite and 1/8 Duroc, 1/8 Meishan, 1/8 Fengjing, or 1/8 Minzhu pigs.
AB - Pigs were the progeny of White Composite boars mated to gilts that were either
1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu and the remainder 3/4 White
Composite. One-eighth Meishan and 1/8 Fengjing pigs averaged approximately .5
more nipples than 1/8 Duroc pigs and .2 more nipples than 1/8 Minzhu pigs (P <
.05), respectively. Duroc, Meishan, and Minzhu crosses did not differ (P > .05)
for survival at birth or at 14 and 28 d. Fengjing crosses had a lower survival
rate (P < .05) at all three ages than Duroc and Meishan crosses. Duroc crosses
were heavier (P < .05) than Chinese crosses at birth. At 56 d, Duroc and Meishan
crosses did not differ (P > .05) for BW, but both were heavier (P < .05) than
Minzhu crosses. Body weight at 70 d did not differ significantly (P > .05) among
breed types. Duroc crosses were heavier (P < .05) than any of the Chinese crosses
at 98, 126, and 154 d of age. At 154 d, Fengjing crosses were lighter (P < .05)
than Meishan or Minzhu crosses. The effect of breed type was not detected for
average probe backfat thickness of gilts at 99.7 kg. Duroc crosses consumed the
most feed, and Fengjing crosses consumed the least during each interval and
during the total period (P < .05). Feed consumption of Meishan and Minzhu crosses
was intermediate to and significantly (P < .05) different from that of Duroc and
Fengjing crosses. At 184 d of age, breed types did not differ (P > .16) for
measures of carcass fat thickness, marbling score, color score, and firmness
score. At 184 d of age, weights of all carcass cuts were heavier (P < .05) for
Duroc than for Chinese crosses with the exception of untrimmed loin weight of
Minzhu crosses. There were few significant differences among breed types when
carcass traits were compared at a constant carcass weight, although Duroc crosses
generally were superior. Relative to similar Duroc crosses, these results suggest
that 1/8 Chinese pigs would grow less rapidly (P < .05) and produce less weight
of trimmed lean cuts at a constant carcass weight.
PMID- 9655575
TI - Reproduction of 3/4 White Composite and 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or
1/4 Minzhu gilts and sows.
AB - Females were either 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu, and the
remainder were 3/4 White Composite. A greater percentage of Fengjing crosses
reached puberty than Duroc or Minzhu (P < .05), and Meishan crosses were
intermediate and not different (P > .05) from other breed types. After adjusting
for differences in percentage detected owing to termination of observation for
estrus, breed types ranked Fengjing, Meishan, Minzhu, and Duroc from youngest to
oldest at puberty with approximately 14 d between adjacent breed types. Meishan
and Fengjing crosses had a greater (P < .05) ovulation rate than Minzhu or Duroc
crosses. With the exception of number of fetuses at 100 d and average fetal
weight at 60 d, differences among breed types were not detected (P > .05) for
litter or uterine traits measured on gilts slaughtered at 60 or 100 d of
gestation. Total number of pigs born was greater (P < .05) for 1/4 Fengjing than
for 1/4 Duroc gilts. Gestation length, number born alive, number weaned, litter
birth weight, or litter weaning weight for gilts did not differ (P > .05) among
breed types. Duroc crosses were heavier (P < .01) than Chinese crosses at d 1 and
28 after farrowing, but breed types did not differ (P > .05) for backfat
thickness at those times. Breed types did not differ (P > .05) for the ratio of
litter gain from 0 to 28 d/total Mcal or any of the component traits in the
ratio. Postweaning estrus activity, conception rate, and litter and uterine
traits of sows bred for second parity were not affected (P > .05) by breed type.
These analyses indicate that crossbred gilts containing 1/4 Meishan, 1/4
Fengjing, or 1/4 Minzhu will reach puberty earlier, have larger litters, and
weigh less at first parity than gilts containing 1/4 Duroc, but they do not have
any significant advantage in litter size at second parity.
PMID- 9655576
TI - Heat tolerance in Tuli-, Senepol-, and Brahman-sired F1 Angus heifers in Florida.
AB - We investigated heat tolerance and growth rate in two trials under ambient
conditions in central Florida. Trial 1 (1994) involved 38 Brahman (B), 21 Senepol
(S), 19 B x Angus (A), 20 S x A, and 20 Tuli (T) x A heifers. Trial 2 (1995)
involved 13 A, 35 B, 30 S, 23 B x A, 17 S x A, and 28 T x A heifers. Measurements
were made on three consecutive weeks during the hotter and cooler seasons of each
year and included rectal temperature (RT, degrees C), respiration rate (RR, bpm),
temperament score (TS; 1 = very docile, 5 = very aggressive), blood packed-cell
volume (PCV), and plasma cortisol concentration (CORT). Data for RT were
transformed (log10 [RT - 37]) before analysis. On the hottest date in Trial 1,
log10 RT was not different between B (.39 +/- .011) and B x A (.37 +/- .016) or
between T x A (.35 +/- .015) and B x A, but log10 RT was lower (P < .05) in S x A
(.30 +/- .015) than in either S (.35 +/- .015) or T x A. On all dates in Trial 1,
RR was lower (P < .05 to .001) and PCV was higher (P < .05 to .001) in B than in
B x A. There were few differences in TS except on two dates when B scored higher
(P < .01 to .001) than B x A, and these differences were associated with higher
(P < .05) CORT in B than in B x A. Using initial BW as a covariate, adjusted ADG
(kg) of T x A (.52 +/- .023) was not different from adjusted ADG of B x A (.57 +/
.024) or S x A (.54 +/- .023). On the hottest date in Trial 2, log10 RT and RR
were higher (P < .001) in A (.59 +/- .017, 74 +/- 2.7) than in B (.47 +/- .010,
39 +/- 1.6), S (.42 +/- .011, 50 +/- 1.8), and crossbred heifers (.47 +/- .011,
60 +/- 1.8; .43 +/- .014, 55 +/- 2.4; and .50 +/- .012, 48 +/- 2.0 for T x A, S x
A and B x A, respectively), and RR was higher (P < .001) in B x A than in B. On
the coolest date in Trial 2, RR was slightly lower in B (32 +/- .5) than in A(34
+/- .7, P < .01) and B x A (36 +/- .6, P < .001) and was associated with higher
PCV in B than in A. On both dates, TS and CORT were higher (P < .01) in B than in
A. In Trial 2, adjusted ADG (kg) was higher (P < .01) in B (.43 +/- .017) than in
A (.32 +/- .033), higher (P < .001) in S (.45 +/- .018) than in A, and higher (P
< .001) in crossbreds (B x A [.53 +/- .023] + S x A [.44 +/- .025] + T x A [.46
+/- .019]) than in A. These data indicate that heat tolerance in F1 crosses of
tropically adapted breeds (Tuli, Senepol, Brahman) with a temperate breed (Angus)
is similar to heat tolerance displayed by purebred tropical breeds (Senepol,
Brahman).
PMID- 9655577
TI - Eating barley too frequently or in excess decreases lambs' preference for barley
but sodium bicarbonate and lasalocid attenuate the response.
AB - We conducted experiments to determine whether preference for barley was affected
when lambs ate various amounts of barley and whether lambs ate more barley when
it contained lasalocid and sodium bicarbonate (NaHCO3), both of which attenuate
acidosis. In Exp. 1, lambs were assigned to two treatments (six lambs/treatment).
For 2 d, lambs in two treatments were offered either 400 or 1,200 g of rolled
barley from 0600 to 0700 as a preload meal. A preference ratio [PR = barley
ingested/(total amount of alfalfa + barley ingested)] was calculated based on
lambs' intake when offered a choice of 200 g each of rolled barley and alfalfa
pellets hourly from 0700 to 1100. After the preload meal, lambs in Treatment 1
(400 g preload) showed equal preference for barley (.52) and alfalfa (.48) for 4
h on d 1 (P > .05); their preference for barley was less after the meal of barley
on d 1 (.52) than on d 2 (.72), but their preference for barley declined between
h 3 (.81) and 4 (.55) of d 2 (P = .11). Lambs in Treatment 2 (1,200 g preload)
showed a low preference for barley on d 1 (.29) and 2 (.19) (P < .001). In Exp.
2, lambs were assigned to four treatments (six lambs/treatment): 1) rolled barley
+ NaHCO3 (2%) + lasalocid (33 ppm); 2) rolled barley + NaHCO3 (2%); 3) rolled
barley + lasalocid (33 ppm); or 4) rolled barley. Intake of barley by lambs
offered NaHCO3 + lasalocid (Treatment 1) was greater (P = .07) than that by lambs
offered NaHCO3 (Treatment 2), whereas intake by lambs offered lasalocid
(Treatment 3) was similar (P > .05) to that by controls. We conclude that eating
barley too frequently or in excess caused a decrease in lambs' preference for
barley and that NaHCO3 and lasalocid attenuated the aversion.
PMID- 9655578
TI - Evidence for three adult fast myosin heavy chain isoforms in type II skeletal
muscle fibers in pigs.
AB - Three main fiber types (one slow [type I] and two fast [type IIA and IIB] can be
distinguished using conventional actomyosin ATPase (AM-ATPase) histochemistry
after acidic pretreatment in mature pig skeletal muscle. We report the isolation,
characterization, and identification of four adult 3'-untranslated regions
corresponding to types I, IIA, IIB, and IIX myosin heavy chains (MyHC) from a
cDNA library. Identification of different type II clones was based on sequence
homology, in situ hybridizations (ISH), AM-ATPase histochemistry, and
immunocytochemistry. Enzyme histochemistry, immunocytochemistry, and ISH were
performed on serial transverse sections of longissimus and red portion of
semitendinosus muscle. Results showed that all three fast MyHC transcripts were
expressed in the longissimus, whereas only type IIA and IIX transcripts were
present in deep red semitendinosus muscle. Type I and IIA fibers contained mostly
type I and IIA transcripts, respectively, whereas type IIB fibers contained a
heterogeneous population of transcripts. In longissimus muscle, 18, 31, and 51%
of conventional IIB fibers were pure IIX, hybrid IIX/IIB, and pure IIB fibers,
respectively. Conversely, conventional IIB fibers were actually IIX in deep red
semitendinosus muscle. Expression of the three fast adult MyHC isoforms in
longissimus was spatially regulated around the typical islets of type I fibers
encountered in pig skeletal muscle. Thus, IIA fibers were contiguous to type I
fibers, pure IIX fibers were in the direct vicinity of type I and IIA fibers, and
hybrid IIX/IIB fibers were located mostly within primary fascicles between the
islets of type I fibers; however, pure IIB fibers were located mainly at the
periphery of the rosettes near the edges of primary fascicles. In light of the
present study, conventional IIB fibers, as defined with AM-ATPase staining, are a
heterogeneous population that should be split into pure IIX, hybrid IIX/ IIB, and
pure IIB fibers for a more accurate fiber typing.
PMID- 9655579
TI - Prediction of slaughter cow composition using live animal and carcass traits.
AB - Slaughter cows (n = 120), representing four genotypes (British, continental, Bos
indicus, and dairy) and three body condition classes (thin, moderate, and fat), n
= 10 per subclass, were used to identify practical and accurate prediction
equations for the yield of boneless manufacturing beef of specific fat
percentages. Cows and their carcasses were weighed and evaluated for USDA yield
and quality grade factors and for physical muscle and fat indicators. Carcass
sides were fabricated; total fat percentage (TFP) was calculated as total fat
(trimmed and chemical) divided by side weight, and tissue lean percentage (TLP)
was calculated as boneless fat-free lean divided by soft tissue weight. Data were
analyzed using maximum R2 multiple regression. The best live trait prediction
model for TFP included live preliminary yield grade (LPYG), body condition score
(LCOND), visual live muscle score (LMUSC), and live weight (LWT), R2 = .83. The
best carcass trait TFP prediction model included adjusted preliminary yield grade
(CPYGA); kidney, pelvic, and heart fat adjustment (CKPHADJ); marbling score
(CMARB); and hot carcass weight (HCW), R2 = .92. The best live trait TLP
prediction model included LPYG, LCOND, LMUSC, and LWT, R2 = .82. The best carcass
trait TLP prediction model included CPYGA, CKPHADJ, CMARB, and lean maturity, R2
= .91. These data indicate that TFP and TLP of slaughter cows can be accurately
and practically predicted using live animal and carcass traits.
PMID- 9655580
TI - Relative contributions of subcutaneous and intermuscular fat to yields and
predictability of retail product, fat trim, and bone in beef carcasses.
AB - Carcass data from one side of 610 steers born from 1988 to 1990 in Cycle IV of
the Germ Plasm Evaluation research program were analyzed to develop means for
carcass traits and retail product percentages at two fat trim levels (.76 and .00
cm) by yield grade categories. Weights of subcutaneous (s.c.) fat and
intermuscular (i.e.m.) fat were recorded separately at each trim level. Quadratic
regression curves were plotted for percentages of roast and steak meat (R&S),
retail product (RP), and fat trim components relative to incremental changes in
USDA yield grade. Prediction equations were developed on a randomly chosen half
of the 610 carcasses to predict weights and percentages of R&S, RP, and fat trim
using carcass traits obtained at the time of USDA grading and then tested on the
remaining half of the carcasses. In addition, prediction equations were developed
using s.c. and i.e.m. fat plus carcass traits to evaluate the contribution of
each to carcass fabrication yields. Percentage of RP, trimmed to either .76 cm or
.00 cm of fat, decreased by an average of 3.5% for each full yield grade
increase. Trimming to .00 cm of fat resulted in about 5.3% less RP compared to
trimming to .76 cm. A prediction equation for percentage of RP trimmed to .00 cm
using adjusted fat thickness, carcass weight, longissimus muscle area, and
percentage of kidney knob had an R2 value of .54. The variations in percentage of
R&S and percentage of RP at both trim levels were reduced by removing s.c. fat
trimmed to .76 cm; however, considerable variation still existed. Subcutaneous
fat expressed as a percentage of the sum of i.e.m. and s.c. fat increased as
yield grade increased, but the percentage of i.e.m. fat was higher than the
percentage of s.c. fat for all yield grades. On the basis of partial correlation
coefficients, i.e.m. fat was approximately twice as important as s.c. fat in
accounting for variations in fabrication yields.
PMID- 9655581
TI - Retail yield and fabrication times for veal as influenced by purchasing options
and merchandising styles.
AB - Twenty-nine selected styles of subprimals or sections of veal were obtained from
a commercial facility to assist in the development of a support program for
retailers. They were fabricated into bone-in or boneless retail cuts and
associated components by trained meat cutters. Each style selected (n = 6) was
used to generate mean retail yields and labor requirements, which were calculated
from wholesale and retail weights and processing times. Means and standard errors
for veal ribs consisting of five different styles (n = 30) concluded that style
#2, 7-rib 4 (10 cm) x 4 (10 cm), had the lowest percentage of total retail yield
(P < .05) owing to the greatest percentage of bone. Furthermore, rib style #2
required the longest total processing time (P < .05). Rib styles #3, 7-rib chop
ready, and #5, 6-rib chop ready, yielded the greatest percentage of total retail
yield and also had the shortest total processing time (P < .05). Within veal
loins, style #2, 4 (10 cm) x 4 (10 cm) loin kidney fat in, had the greatest
percentage fat (P < .05). Loin styles #2 and #3, 4 (10 cm) x 4 (10 cm) loin
special trimmed, generated more lean and fat trimmings and bone, resulting in
lower percentage of total retail yields than loin style #1, 0 (0 cm) x 1 (2.5 cm)
loin special trimmed (P < .05). Results indicated that bone-in subprimals and
sections required more processing time if fabricated into a boneless end point.
In addition, as the number of different retail cuts increased, processing times
also increased.
PMID- 9655582
TI - Differences in natural steroid hormone patterns of beef from bulls and steers.
AB - This investigation gives an overview of the concentrations of naturally occurring
androgens, progestogens, corticosteroids, and their precursors and metabolites in
meat from bulls and steers. A recently developed gas chromatography-mass
spectrometry IGC-MS) method with improved sensitivity for steroid analysis was
used. Eighty-two beef samples were analyzed using the GC-MS method. Beef from
bulls contained higher concentrations of testosterone, which is an anabolic
androgen, and its metabolite epitestosterone (P < .01) and the androgen precursor
dehydroepiandrosterone (P < .05) than beef from steers. Beef from steers
contained higher (P < .05) concentrations of the basic hormone precursor
pregnenolone and cortisol, which is a catabolic corticosteroid, than beef from
bulls. A classification of an unknown beef sample to one of the categories (bull
or steer) was possible in most cases (>90%) using a masculinity index (MI) that
was calculated using the concentrations of testosterone, epitestosterone, and
pregnenolone. Because the hormonal status of beef cattle is related to meat
quality characteristics, such as tenderness or fat and protein distribution, the
MI may contribute to meat quality assessment and meat quality control.
PMID- 9655583
TI - Selected lignosulfonate fractions affect growth performance, digestibility, and
cecal and colonic properties in rats.
AB - We determined the effects of lignosulfonate (LS) on nutrient digestibility and on
hindgut fermentation characteristics using 80 adult male Sprague-Dawley rats fed
a control diet or a diet containing 3% (dry matter basis) of seven selected LS
fractions. Lignosulfonate fractions were divided into three categories: two
fractionated whole calcium spent sulfite liquors (CaSSL) and one low-molecular
weight permeate of CaSSL designated as WholeLS 1, 2, and 3, respectively; two
extracted sodium LS (NaLS) fractions denoted as HighLS 1 and 2 (high percentage
of NaLS); and two concentrated sugar solutions designated as LowLS 1 and 2 (low
percentage of NaLS). All diets containing LS were less digestible (P < .001) than
the control diet. Lignosulfonate treatment had a variable effect on short-chain
fatty acid concentration except for LowLS 1, which tended to enhance butyrate
concentration. Cecal organ weights were greater (P < .001) for LS treatments, but
there was no difference in colonic organ weights. All cecal and colonic pH
values, except the cecal pH for HighLS 2, were lower (P < .001) for LS treatment
groups. Colonic Bifidobacterium increased (P < .005) with WholeLS 1 and 3 and
HighLS 2 treatments. Cecal Lactobacillus levels were increased (P < .001) by
WholeLS 1 and 2, LowLS 2, and HighLS 2. Results show that ingestion of selected
LS fractions can modify digestive physiology and gastrointestinal tract
characteristics of rats.
PMID- 9655584
TI - L-ascorbyl-2-polyphosphate as a vitamin C source for segregated and
conventionally weaned pigs.
AB - We conducted two experiments to evaluate the efficacy of a stable source of
vitamin C for improving performance and iron status in early-weaned pigs. A
preparation of L-ascorbyl-2-polyphosphate (Rovimix Stay-C 25, Roche Vitamins,
Ames, IA and Bramus, NJ), which supplies 25% ascorbic acid activity in a stable
form, served as the vitamin C source and was incorporated at dietary vitamin C
levels of 0, 75, or 150 ppm. In Exp. 1, 72 pigs (14 +/- 2 d of age and 4.98 kg
BW) were blocked based on initial BW and penned in groups of three (eight pens
per treatment) in an off-site nursery for 42 d. Phase 1 lasted from d 0 to 14,
Phase 2 from d 14 to 28, and Phase 3 from d 28 to 42 after weaning. Daily gain
and gain:feed ratio (G/F) increased during Phase 1 (quadratic, P < .1 and P <
.05, respectively), Phase 3 (linear, P < .1 and P < .01, respectively), and for
the overall 42-d experiment (linear, P < .05 and P < .1, respectively) in
response to increasing dietary vitamin C. At 14 d after weaning, plasma vitamin C
increased (linear, P < .05) with increasing dietary vitamin C, but plasma iron,
hemoglobin, and hematocrit were not influenced by dietary vitamin C. In Exp. 2,
120 pigs (20 +/- 3 d of age and 7.2 kg BW) were blocked based on initial BW and
penned in groups of five (eight pens per treatment) in a conventional nursery
system for 31 d. Phase 1 consisted of d 0 to 7, Phase 2 from d 7 to 17, and Phase
3 from d 17 to 31 after weaning. During the period from d 0 to 17 after weaning,
ADG and G/F were improved (linear, P < .1) with increasing dietary vitamin C. At
d 17 after weaning, plasma vitamin C and serum iron increased (linear, P < .05),
but unbound iron-binding capacity and total iron-binding capacity decreased
(linear, P < .05 and P < .1, respectively) with increasing dietary vitamin C.
These results suggest that dietary vitamin C is needed during the first 42 d
after weaning when pigs are weaned as early as 12 d of age and reared in an off
site nursery and during the first 17 d after weaning when pigs are weaned as
early as 17 d of age and reared in a conventional nursery system. L-Ascorbyl-2
polyphosphate at a supplemental level of 75 ppm was adequate to meet the dietary
vitamin C requirement of early-weaned pigs. Vitamin C supplementation with a
stable product will improve performance in young pigs during the high-stress
postweaning period and may be particularly beneficial to pigs weaned at a very
early age.
PMID- 9655585
TI - Effect of ergotamine and ergonovine on plasma concentrations of thyroid hormones
and cortisol in cattle.
AB - Plasma samples from two experiments were processed to determine whether ergot
alkaloids associated with endophyte-infected tall fescue altered peripheral
thyroxine (T4), triiodothyronine (T3), or cortisol concentrations in cattle. In
Exp. 1, seven Angus steers (294 kg) received i.v. bolus injections of saline
(SAL), ergonovine maleate (7 mg; EM), or ergotamine tartrate (7 mg; ET) at weekly
intervals, and they received all treatments during the study. Blood was sampled
every 15 min for 5 h, and treatments were given after h 1. Mean ambient
temperature was 34 degrees C. Treatment x time affected plasma concentrations of
T3 (P < .05) and of cortisol (P < .001) but not that of T4 (P > .2). Plasma T3
concentrations were not affected by SAL, whereas concentrations increased (P <
.01) after either EM or ET treatment. Plasma cortisol concentrations were not
altered by SAL or EM, but they were increased (P < .001) by ET treatment. In Exp.
2, six Holstein cows (499 kg) nursing calves received a bolus i.v. injection of
SAL, EM (9.5 mg), or ET (9.5 mg) per estrous cycle, and all treatments were given
over three cycles. Blood was sampled every 20 min for 5 h; treatments were given
after h 1. Mean ambient temperature was 26 degrees C. Treatment x time affected
T3 (P = .08) and cortisol (P < .001) and tended to influence (P = .16) T4
concentrations. Plasma T3, T4, and cortisol concentrations were not influenced by
SAL treatment. Plasma T3 was higher (P < or = .01) after EM or ET treatment
compared with pretreatment concentrations. Concentrations of T4 during the 4 h
after EM and ET were increased (P < .001) compared with pretreatment. Plasma
cortisol concentrations were not altered by EM but were increased (P < .001) by
ET. Ergot alkaloids implicated as contributing agents to fescue toxicosis alter
plasma concentrations of hormones important to metabolic and thermoregulatory
functions in cattle.
PMID- 9655586
TI - Functional activity of antibodies at the bovine beta2-adrenoceptor.
AB - Antibodies that can activate beta2-adrenoceptors (beta2-AR) have the potential to
mimic the anabolic effects of beta-agonist drugs, such as clenbuterol. In this
study, antibodies were raised in rabbits against two peptide analogues of the
human beta2-adrenoceptor (beta2-AR): One peptide corresponded to the complete
second outer loop of the receptor (24 amino acids; H24T), and the second peptide
was a truncated version of the first (13 amino acids; H13C). Following affinity
purification, the antibodies were screened to detect interaction with beta2-AR in
vitro. Membrane proteins from transformed Escherichia coli that express the beta2
AR were separated using SDS PAGE and transferred to nitrocellulose sheets.
Immunoblotting revealed a single protein band (39,000 Da) that was recognized by
the affinity-purified anti-H24T antibodies. However, the anti-H13C antibodies did
not recognize any protein bands in immunoblots. In ligand binding studies, anti
H24T antibodies at a concentration of 50 nM, increased the affinity (KD) of the
radiolabeled antagonist [125I]iodocyanopindolol for the bovine beta2-AR from 31.7
pM to 25.3 pM (P < .05) without changing the receptor number. Anti-H13C
antibodies had no effect on ligand binding. In competitive ligand binding
experiments, there was no effect of antibodies on the affinity of bovine beta2-AR
for the agonist (-)-isoproterenol. However, functional activity of anti-H24T
antibodies was demonstrated in an organ bath study. The presence of antibodies
caused a leftward shift in the concentration-response curve for (-)-isoproterenol
induced relaxation of isolated bovine smooth muscle strips. Values for pD2 (-log
EC50) were reduced in the presence of 10 nM antibody (8.62 +/- .11) compared to
controls (8.30 +/- .08; P < .05). Anti-H13C antibodies had no effect on (-)
isoproterenol-induced smooth muscle relaxation. These studies have demonstrated
recognition, interaction, and functional activity of site-directed antibodies at
the beta2-AR. Further studies will determine whether antibodies that potentiate
activity at the beta2-AR may be evoked by the active immunization of cattle with
the peptide H24T, and if so, whether this will cause the repartitioning of
nutrients in a manner analogous to conventional beta2-agonists and thus provide
an alternative to the use of xenobiotic compounds.
PMID- 9655587
TI - Induced and synchronized estrus in cattle: dose titration of estradiol benzoate
in peripubertal heifers and postpartum cows after treatment with an intravaginal
progesterone-releasing insert and prostaglandin F2alpha.
AB - Peripubertal beef heifers (n = 57) and postpartum multiparous cows (n = 52) were
used to determine the optimal dose of estradiol benzoate (EB) to induce and
synchronize estrus after treatment with intravaginal progesterone inserts (IVP4,
EAZI-BREED CIDR). All females received an IVP4 for 7 d (d 0 = insertion day) with
a 25-mg injection of PGF2alpha (Lutalyse) on d 6. At 24 to 30 h after IVP4
removal, females were randomly assigned to be injected subcutaneously with EB at
the following doses: heifers 0, .2, .38, or .75 mg and cows 0, .25, .5, or 1 mg.
Furthermore, seven heifers and seven cows from each dose group were bled every 4
h for 76 h starting at EB injection. Serum was collected and assayed for LH and
estradiol-17beta (E2). Observations for signs of estrus were made twice daily for
21 d after removal of IVP4, and females were artificially inseminated 8 to 20 h
after detection of estrus. The percentage of females showing estrous behavior was
increased by EB (P < .04); the greatest response was at .38 mg in heifers (86%)
and 1 mg in cows (100%). Dose x time interaction affected (P < .01) E2
concentrations in heifers and cows; the animals that received the higher doses of
EB had greater E2 concentrations in a shorter time than those that received the
smaller doses. The percentage of cows and heifers with an acute preovulatory LH
release (peak LH) was affected by dose, with a linear (P < .01) and a quadratic
(P < .01) response. Highest concentrations of LH during peak LH were affected by
dose with a linear (P < .01) response in heifers and linear (P < .01) and
quadratic (P < .08) responses in cows. Heifers receiving .38 mg and cows
receiving .5 and 1 mg of EB had the highest peak LH. Time to LH peak had a linear
(P < .03) response in heifers and had linear (P < .04) and quadratic (P < .05)
responses in cows. Pregnancy rate was affected (P < .02) in heifers by whether or
not they were anestrous before IVP4 treatment (those with estrous cycles = 52% vs
those that were anestrous = 22%) and in cows by dose of EB (P < .01; 8, 23, 21,
and 67% for 0, .25, .5, and 1 mg, respectively). In conclusion, in females
treated with IVP4 and PGF2alpha to induce and synchronize estrus, an injection of
EB increased concentrations of E2 and LH and increased number of animals showing
estrus. Also, EB increased pregnancy rates in cows. Optimal responses were at .38
mg EB for heifers and at 1 mg EB for cows.
PMID- 9655588
TI - Expression of the angiogenic factors, basic fibroblast growth factor and vascular
endothelial growth factor, in the ovary.
AB - In adult tissues, vascular growth (angiogenesis) occurs normally during tissue
repair, such as in the healing of wounds and fractures. Inappropriate vascular
growth is associated with various pathological conditions. These conditions
include tumor growth, retinopathies, hemangiomas, fibroses, and rheumatoid
arthritis in the case of rampant vascular growth and nonhealing wounds and
fractures in the case of inadequate vascular growth. The female reproductive
organs exhibit dramatic, periodic growth and regression, accompanied by equally
dramatic changes in their rates of blood flow. Thus, it is not surprising that
they are some of the few adult tissues in which angiogenesis occurs as a normal
process. Ovarian follicles and corpora lutea contain and produce angiogenic
factors. These angiogenic factors bind heparin and seem to belong to the
fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF)
families of proteins. Based on our studies of the pattern of expression of FGF
and its major receptors in bovine, ovine, and porcine corpora lutea, we have
suggested that FGF may influence not only luteal cell proliferation but also cell
death, thereby regulating cell turnover in the luteal vascular and nonvascular
compartments. In addition, we recently have shown that luteal expression of VEGF
is greatest during the early luteal phase, coincident with luteal
vascularization. Moreover, VEGF is present exclusively in luteal connective
tissue and perivascular (arteriolar smooth muscle and capillary pericyte) cells.
In fact, the first thecal-derived cells to invade the granulosa-derived regions
immediately after ovulation seem to be VEGF-containing pericytes. We have
therefore hypothesized that ovarian pericytes play a key role in vascularization
of developing follicles and corpora lutea. Further understanding of the specific
physiological roles of these factors in follicular and luteal growth,
development, and function will ultimately lead to improved methods of regulating
fertility.
PMID- 9655589
TI - Influence of season on dietary composition, intake, and digestion by beef steers
grazing mixed-grass prairie in the northern Great Plains.
AB - We used six beef steers (377 +/- 12.7 kg) to evaluate the effect of advancing
season on dietary composition, forage intake, and digestion. Six 10-d sample
collections were conducted from mid-June to mid-December 1995. Diet quality data
demonstrated a linear (P < .01) decline in CP and in vitro OM digestibility
(IVOMD), whereas NDF, ADF, acid detergent-insoluble CP (ADICP; percentage of CP),
and undegradable intake protein (UIP; percentage of CP) increased linearly (P <
.01) with advancing season. Fecal output and ruminal OM fill (percentage of BW)
demonstrated linear and cubic responses (P < .10) across the grazing season.
Intake of OM (percentage of BW) followed quadratic and cubic (P < .10) patterns
across season. Rate (percentage per hour) of in situ NDF disappearance (ISNDFD)
decreased and lag time increased linearly (P < .01) with advancing season.
Likewise, quadratic (P < .07) and cubic (P < .06) responses were observed for
rate and lag time of ISNDFD. The rapidly degraded CP fraction increased (P < .10)
linearly, and the rate of in situ CP disappearance (ISCPD) followed a linear and
quadratic decrease (P < .10) with advancing season. In summary, these data
indicate decreases (P < .10) in dietary CP, IVOMD, ISNDFD, and ISCPD with
advancing season. In addition, seasonal increases (P < .10) in forage NDF, ADF,
ADICP, UIP (percentage of DM) and fecal output were observed and correspond to
the grazing of increasingly mature forage. These data suggest that mixed-grass
range forage consumed by cattle in western North Dakota during November and
December is deficient in degradable intake protein (DIP). Investigation of
protein supplementation (particularly DIP) during these times is warranted.
PMID- 9655590
TI - Performance and digestion by steers grazing tall fescue and supplemented with
energy and protein.
AB - We studied the effects of different levels of protein and energy supplementation
on BW gains and sites of nutrient digestion in steers grazing the primary growth
of endophyte-infected tall fescue (Festuca arundinacea Schreb cv. Kentucky 31).
Angus steers (n = 168; mean BW = 246.8 +/- 15.0 kg) grazed tall fescue without
supplementation (C) or were supplemented with 1.4 kg/d of cracked corn (CC1), 1.4
kg/d of corn gluten feed (CGF1), 2.8 kg/d of CC (CC2), 2.8 kg/d of CGF (CGF2), or
.7 kg/d of cornstarch and .7 kg/d of corn gluten meal (CS-CGM) during an 85-d
period in a randomized complete block design. Supplemented steers (S) had a
higher (P = .03) ADG than the control steers (.64 vs .74 kg/d). There was an
interaction (P = .02) between supplement type and level. Supplementation during
the grazing period had no effect on subsequent feedlot ADG (average 1.3 kg/d). In
a digestion study, Angus x Simmental steers (n = 4; 412 +/- 20.4 kg) fitted with
cannulas in the esophagus, rumen, and duodenum grazed tall fescue (C), C + 3.1
kg/d CGF, C + 3.1 kg/d of cracked corn (CC), or C + 1.4 kg/d CS-CGM over four
experimental periods in a Latin square design. The ruminal ammonia nitrogen
concentration tended to be higher (P < .09) in C than in CGF and in CC (21.9 vs
19.2 mg/dL), but ruminal pH and total VFA concentration did not differ among
treatments. Forage OM intakes were lower (P < .05) in steers supplemented with CC
or CGF (an average of 7,570 g/d) than in C (9,658 g/d). Total OM intakes and
digestibilities did not differ (P > .10) among treatments. Duodenal N flows and
efficiencies of net ruminal microbial protein synthesis were not different (P >
.10) among treatments. Supplementation of steers grazing primary growth of tall
fescue improved animal gain but did not have a great effect on ruminal
fermentation, OM digestion, or net ruminal microbial protein synthesis.
PMID- 9655591
TI - Calculation of the buffering capacity of bicarbonate in the rumen and in vitro.
AB - We describe a model to calculate the buffering capacity of bicarbonate in the
rumen. The addition of NaHCO3 results in the release of CO2 from solution and
eventually from the rumen via eructation. This process directly neutralizes
ruminal acidity. The degree to which the process continues depends on the partial
pressure of CO2 in the gas phase, the pH, and a constant (7.74), according to the
Henderson-Hasselbalch equation: pH = 7.74 + log([HCO3-]/pressure of CO2 in
atmospheres). The addition of NaHCO3 to buffer solutions and ruminal fluid under
high pressure of CO2 increased pH as predicted. The buffering capacity of ruminal
fluid under CO2 was greater at low pH than was previously determined by titration
in air. In contrast, in vitro systems in which CO2 is not permitted to escape may
result in reduced buffering capacity. In vitro systems in which excess CO2 may
escape (under N2 gas pressure) may result in uncontrolled pH elevation. Dilution
of ruminal fluid under constant pressure of CO2 decreased ruminal pH as predicted
by the model. The pH under different pressures at equilibrium and the buffering
capacity are easily calculated for in vitro and in vivo systems.
PMID- 9655592
TI - The effect of teaching approaches on achievement and satisfaction of field
dependent and field-independent learners in animal science.
AB - A senior-level university swine management class of 42 students consisted of
three laboratory sections (containing 22, 12, and 8 students). A counterbalanced
design was used to evaluate three teaching approaches (field-dependent, field
independent, and combination); each weekly laboratory section received each
teaching approach for 3 wk. All students were evaluated and categorized as field
dependent or field-independent learners before the study. All students were
evaluated for achievement and satisfaction at the end of each laboratory period.
Teaching approach x learning style x laboratory section was not significant for
achievement or satisfaction. Teaching approach x laboratory section was
significant for achievement (P = .01) and satisfaction (P = .01). Teaching
approach x learning style was not significant for achievement (P = . 15) or
satisfaction (P = .15). Field-independent learners scored 6% higher on
achievement tests when taught with a field-dependent approach rather than a field
independent approach. Field-dependent learners scored 21.9% higher when taught
with a combination approach rather than a field-dependent approach and 13.8%
higher than when taught with a field-independent approach. Overall student
satisfaction was positive (3.50 on a 5-point scale). Field-independent learners
were most satisfied with a combination approach; however, field-dependent
learners preferred a field-dependent approach. Teaching approach was significant
(P = .03) for achievement with the combination approach and resulted in higher
scores (8.7 to 9.7%). Teaching approach was not significant for satisfaction (P =
.61). Overall, a combination of teaching methods, tailored to both field
dependent and field-independent students, was most effective. Matching
instruction to student learning style is not necessary. The study represents an
example of using animal science students and faculty in research to improve
animal science instruction and heighten awareness of teaching methods.
PMID- 9655593
TI - Rapid communication: A PCR-RFLP marker at the porcine complement factor B gene
locus shows between-population frequency variation.
PMID- 9655594
TI - Rapid communication: a PCR amplified product length polymorphism (APLP) marker at
the porcine glucosephosphate isomerase locus shows between-population frequency
variation.
PMID- 9655595
TI - Rapid communication: Nucleotide sequence of the coding region for the porcine
beta1-adrenergic receptor gene.
PMID- 9655596
TI - Which afferents induce and transmit dorsal root reflex in rats?
AB - The dorsal root reflex (DRR) in single fibers, recorded in the severed L5 dorsal
root central stump, initiated spontaneously or by electric stimulation (St) of
sciatic nerve, was studied in anesthetized rats. The excitation of group II
afferents were the major inputs to induce DRRs which were transmitted mainly in
fibers with conduction velocity below 20 m/s, and its central delay was 3-5 ms.
The firing frequency of both spontaneous and evoked DRRs were increased two to
four times after spinalization (T13). These results suggested that the DRR may
play an important role in the modulation of sensory afferent inputs regulated by
supraspinal structures.
PMID- 9655597
TI - Regional changes of NADPH-diaphorase and neuropeptide Y neurons in the cerebral
cortex of aged Fischer 344 rats.
AB - This study examined the effects of aging on neuropeptide Y (NPY) and NADPH
diaphorase (NADPH-d)-positive neurons of the cerebral cortex in young (3 months)
and aged (24 months) Fischer 344 rats by immunohistochemical and histochemical
methods. In the aged group, the number of NPY-immunoreactive (IR)/NADPH-d
positive neurons was not significantly changed in all regions of the cerebral
cortex compared to the control group. However, the number of NPY-IR/NADPH-d
negative neurons was significantly decreased in frontal association, primary
motor, secondary somatosensory, insular, ectorhinal, perirhinal and auditory
cortex in the aged group. In the aged rats, about 5-10% of NPY-IR/NADPH-d
positive neurons were dystrophic and scattered within the cerebral cortex. These
results suggested that NPY-IR neurons that do not contain NADPH-d are affected by
aging and that aging influences NPY-IR/NADPH-d-negative neurons in a region
specific pattern within the cerebral cortex of rats.
PMID- 9655598
TI - Coexpression of phospholipase A2 isoforms in rat striatal astrocytes.
AB - The expression and activity of phospholipase A2 (PLA2) isoforms were investigated
in primary cultures of striatal astrocytes. The calcium ionophore A23187 together
with the protein kinase C activator phorbol ester was the most potent stimulus in
eliciting [3H]arachidonic acid release in the extracellular medium. Reverse
transcription coupled to polymerase chain reaction (RT-PCR) showed the presence
of the 85 kDa cytosolic PLA2 mRNA and the 14 kDa secretory PLA2 mRNA in untreated
astrocytes. Immunoblot experiments with isoform-specific antibodies showed the
presence of the cytosolic PLA2 in untreated astrocytes, while the secretory PLA2
was detected only in lipopolysaccharide-treated astrocytes. These data suggest
that the two PLA2 isoforms expressed in striatal astrocytes might play different
roles in cellular processes mediated by astrocytes.
PMID- 9655599
TI - Ca2+-H+ antiport activity in synaptic vesicles isolated from sheep brain cortex.
AB - Synaptic vesicles isolated from sheep brain cortex exhibit an ATP-dependent Ca2+
accumulation that is inhibited by the protonophore uncoupler carbonyl cyanide m
chorophenylhydrazone (CCCP) and completely released by the Ca2+ ionophore
ionomycin. This transport activity was sensitive to the V-type ATPase inhibitor,
bafilomycin, but not to the P-type ATPase inhibitor, vanadate. We also observed
that the proton gradient, established across the synaptic vesicle membranes in
the presence of ATP, is partially dissipated by the addition of Ca2+ (100-860
microM) in correlation to an increase of ATP hydrolysis by the H+-pumping ATPase.
In contrast, the activity of the H+-ATPase, measured under uncoupling conditions
(presence of CCCP), appears to be unaltered by the calcium ion. The Ca2+-induced
H+ release visualized by fluorescence quenching of acridine orange correlates
well with the Ca2+ uptake determined isotopically. These results indicate that
synaptic vesicles accumulate Ca2+, via a low affinity Ca2+-H+ antiport system
energized by the protonmotive force originated from the H+-pumping ATPase
activity.
PMID- 9655600
TI - Morphological heterogeneity of cultured spinal and cerebral rat oligodendrocytes.
AB - Oligodendrocytes in different central nervous system regions have dissimilar
morphologies. In order to find out if immature oligodendrocytes develop different
phenotypes spontaneously, neonatal spinal and cerebral rat oligodendrocytes were
cultured in vitro in the absence of neurons. The results show that spinal
oligodendrocytes tend to develop a bipolar structure with few processes, while
cerebral cells tend to become multipolar with many processes. A similar spinal
cerebral difference was seen in oligodendrocyte-enriched cultures. Hence, spinal
and cerebral oligodendrocytes develop partly different morphologies in vitro.
PMID- 9655601
TI - Imidazoline receptor proteins in brains of patients with Alzheimer's disease.
AB - Imidazoline receptors (29/30- and 45-kDa proteins) were quantitated in postmortem
brains of patients with Alzheimer's disease (AD) by using immunoblotting
techniques and a specific antiserum. Increased levels of the 29/30-kDa protein
(30%), 45-kDa protein (36%) and glial fibrillary acidic protein (88%) were found
in the frontal cortex of AD patients. These findings are in line with the
reported higher density of imidazoline receptors labelled by [3H]idazoxan in AD
brains, suggesting that these imidazoline receptor proteins are related to the I2
imidazoline receptor located in mitochondria of glial (astrocyte) cells.
PMID- 9655602
TI - Progressive accumbens degeneration after neonatal striatal 6-hydroxydopamine in
rats.
AB - Parkinson's disease is associated with progressive loss of nigrostriatal dopamine
(DA). Models of the disorder, produced with neurotoxins (N-methyl-4-phenyl
1,2,3,6-tetrahydropyridine or 6-hydroxydopamine) that selectively lesion DA
neurons, are characterized by acute removal and gradual recovery of DA. We report
slowly progressive loss of DA in ipsilateral nucleus accumbens following profound
(>90%) acute unilateral depletion of DA in the caudate-putamen of neonatal rats,
from 50% at age 27 days to 94% by 100 days. Metabolic turnover of DA markedly
increased in ipsilateral accumbens, and may yield tissue-damaging neurotoxic by
products. This paradigm may help in elucidating mechanisms responsible for
gradual degeneration of DA neurons and for screening potential neuroprotective
agents.
PMID- 9655603
TI - Role of calcium in the activation of erp72 and heme oxygenase-1 expression on
depletion of endoplasmic reticulum calcium stores in rat neuronal cell culture.
AB - Endoplasmic reticulum (ER) calcium pool depletion was induced by 30 min exposure
of primary neuronal cells to thapsigargin (Tg), an irreversible inhibitor of ER
Ca2+-ATPase. Twelve hours later, erp72 and heme oxygenase-1 (HO-1) mRNA levels
were quantified by PCR. Protein synthesis was also measured. Transient Tg
exposure of neurons induced a marked rise in mRNA levels (7-fold and a 21-fold
increase in erp72 and HO-1 mRNA levels; P < 0.001). Loading of neurons with the
calcium chelator 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'
tetra(acetoxymethyl)ester (BAPTA-AM) prior to thapsigargin treatment had only a
minor effect on the Tg-induced rise in gene expression. This small inhibitory
effect may result from the severe suppression of protein synthesis caused by
BAPTA-AM. The results suggest that the increase in stress gene expression induced
by exposure of neurons to Tg is triggered by a decrease in ER calcium activity
and not by the corresponding increase in cytoplasmic calcium activity.
PMID- 9655604
TI - Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors
expressed in Xenopus oocytes.
AB - The 5-HT3 receptor (5-HT3R) is part of a superfamily of ligand-gated ion channels
which includes nicotinic acetylcholine receptors (nAChR). cRNA derived from the
long isoform cloned mouse 5-HT3R was used to drive expression of 5-HT3Rs in
Xenopus oocytes. 5-HT-induced currents were monitored using two-electrode voltage
clamp. Eight nicotinic agonists, including ACh and nicotine, but not alpha
anatoxin, were found to antagonize 5-HT-induced currents. With the exception of 3
(2,4)-dimethoxybenzylidene-anabaseine (DMXB-anabaseine; GTS-21) this antagonism
appeared to be competitive since it could be overcome by increasing
concentrations of 5-HT. Potency of 5-HT3 antagonism was comparable to reported
values for nAChR alpha7 activation. These results confirm the notion of families
of receptors and further indicate that strong similarities can exist in some
critical binding domains.
PMID- 9655605
TI - Preparation of cell suspensions for co-transplantation: methodological
considerations.
AB - The purpose of the current study was to determine the optimal strategy for
preparing cell suspensions for co-transplantation. In the first experiment, the
number of Sertoli cell (SC) aggregates and the number of tyrosine hydroxylase
positive neurons were compared over time when cell suspensions of Sertoli or
ventral mesencephalic cells were kept as a co-suspension mixed at 0 h. Cells from
each suspension were dispensed onto glass slides in a manner similar to
transplantation. When dispensed in this manner, the number of SC aggregates and
TH-positive neurons decreased over 4 h. In experiment 2, the cell suspensions
were mixed just prior to injection at each of four timepoints, the number of
aggregates and TH neurons was consistent over time. Clearly this latter strategy
resulted consistent recovery of both cell types for transplants up to 3 h after
suspension preparation.
PMID- 9655606
TI - Dynorphin uses a non-opioid mechanism to potentiate N-methyl-D-aspartate currents
in single rat periaqueductal gray neurons.
AB - The interaction of the endogenous K-opioid, dynorphin, with N-methyl-D-aspartate
(NMDA) receptors was studied in single periaqueductal gray (PAG) cells using the
whole cell patch recording technique. We have found that dynorphin A (1-17)
rapidly and reversibly potentiates NMDA-activated currents in a subpopulation of
PAG cells. The potentiation cannot be blocked by the non-specific opioid
antagonist, naloxone, nor can it be reversed by the specific kappa-opioid
antagonist, nor-BNI. In addition, the non-opioid fragment of dynorphin, dynorphin
A (2-17), is effective in potentiating NMDA currents, while the specific kappa
opioid, U50,488, cannot mimic the action of dynorphin A (1-17). The non-opioid
dynorphin action and the rapid onset and recovery of the potentiation are
consistent with the idea that dynorphin interacts directly with NMDA receptors in
PAG cells.
PMID- 9655607
TI - The effect of excitatory aminoacids on GABA release from mediobasal hypothalamus
of female rats.
AB - The purpose of the present study was to examine the in vitro effect of L
glutamate and its agonists on basal and potassium-evoked GABA release from
incubated mediobasal hypothalamus (MBH) of intact, ovariectomized (OVX) and OVX
estrogenized female rats. L-glutamate (100 microM) decreased evoked GABA release
from MBH of intact female rats in diestrus. NMDA and quisqualate (10 and 100
microM) modified neither basal nor evoked hypothalamic GABA release of intact
rats. However, kainate (10 and 100 microM) decreased hypothalamic basal and
evoked GABA release of intact rats. Kainate induced no changes in basal or in
evoked GABA release from hypothalami of OVX rats, but decreased GABA release in
chronically estrogenized rats. DNQX (6,7-dinitroquinoxaline-2,3-dione), a non
NMDA receptor antagonist, failed to affect GABA release but blocked the
inhibitory effect of kainate. The kainate effect was not Mg2+-sensitive and was
not inhibited by D-AP5 (D(-)-2-amino-5-phosphonopentanoic acid), an NMDA-specific
receptor antagonist. Kainate induced no changes in nitric oxide synthase activity
in MBH of either intact or estrogenized rats. These data indicate that kainate
decreases GABA release from MBH of female rats through a non-NMDA receptor
subtype, and provide evidence to support the view that kainate-mediated decrease
of the hypothalamic GABAergic tone is affected by estrogens.
PMID- 9655608
TI - Malic enzyme isoforms in astrocytes: comparative study on activities in rat brain
tissue and astroglia-rich primary cultures.
AB - Anion exchange chromatography on diethylaminoethyl cellulose was optimized to
separate the cytosolic and mitochondrial isoforms of malic enzyme from rat brain.
Extracts of adult rat brain and of astroglia-rich primary cultures derived from
the brains of newborn rats were analyzed for their content of the two isozymes.
In the case of brain tissue 45% of malic enzyme activity was due to the cytosolic
isoform. In contrast, in extracts from astroglia-rich primary cultures more than
95% of the total activity was associated with the cytosolic isozyme. From these
data it is concluded that the cytosolic rather than the mitochondrial isoform of
malic enzyme has prominent functions in astroglial metabolism.
PMID- 9655609
TI - Removal of GABAergic inhibition in the mediodorsal nucleus of the rat thalamus
leads to increases in heart rate and blood pressure.
AB - The mediodorsal nucleus of the thalamus (MD) has connections with central
autonomic centers involved in cardiovascular control and undergoes severe
degeneration in fatal familial insomnia, a human disease characterized by
progressive dysautonomia. Microinjections of the GABAA antagonist bicuculline
methiodide (BMI) into the medial and central portion of the MD lead to
significant, dose-dependent increases in both heart rate and blood pressure.
Similar injections into surrounding regions elicited little to no change. The
data suggest that the medial and central portion of the MD plays a role in
central cardiovascular regulation. Neurons of the MD may be under tonic GABAergic
inhibition, and disruption of circuits at this level may underlie dysautonomia in
many neurological diseases.
PMID- 9655610
TI - Melatonin restores and enhances the human type B tonsillar lymphocyte subset in
recurrent acute tonsillitis.
AB - Tonsils have a privileged situation in the immune system in that they are in
touch with the environment. Melatonin is a hormone that is influenced by the
circadian environmental variations of dark-light and is a modulator of the immune
system. We have studied a group of thirty five children with recurrent acute
tonsillitis that were submitted for tonsillectomy. Tonsillar lymphocyte subsets
were determined before and after culture through flow cytometry in a tonsillar
mononuclear suspension. After the culture, the lymphocyte subsets of type B
suffered a decrease that was restored in the presence of melatonin or
phytohemaglutinin, and even increased above the values of the control when the
culture was accomplished in the presence of both substances. This process was
specific for B cells, no occurrence for T lymphocytes or natural killer cells.
Melatonin is found in the crossroads of the interaction of the microorganisms,
pollens or inert substances with the tonsillar lymphocytes in the production of
the immune defences. Further study is required on tonsillar pathology to explain
its physiopathology and its possible therapeutic role.
PMID- 9655611
TI - Neurons as well as astrocytes express proteoglycan-type protein tyrosine
phosphatase zeta/RPTPbeta: analysis of mice in which the PTPzeta/RPTPbeta gene
was replaced with the LacZ gene.
AB - PTPzeta/RPTPbeta is a receptor-like protein tyrosine phosphatase expressed as a
chondroitin sulfate proteoglycan. We generated mice in which the PTPzeta gene was
replaced by the LacZ gene by gene targeting. Analysis of heterozygous PTPzeta
targeted mice allowed us to identify PTPzeta-producing cells during development
by examining expression of the LacZ gene. LacZ expression was detected only in
the central nervous system throughout development from embryonic day 8.5. In the
postnatal period, subsets of neurons and astrocytes in the brain, including
pyramidal cells and astrocytes in the hippocampus, expressed LacZ. Primary
cultures of cells from the cerebral cortex of embryonic day 16 mice also
indicated that both neurons and astrocytes were positive for LacZ. These results
indicated that neurons and astrocytes express PTPzeta.
PMID- 9655612
TI - Modulation of glutamate sensitivities by inhibitors of a protein kinase and a
protein phosphatase in cultured rat Purkinje cells.
AB - We examined the effects of inhibitors of calcium-calmodulin-dependent protein
kinase II (CaM kinase II) and protein phosphatases on the glutamate (Glu)
responses in cultured rat cerebellar Purkinje cells. CaM kinase II inhibitors
significantly potentiated Glu responses, and activation of metabotropic Glu
receptors facilitated this potentiation. In contrast, a phosphatase inhibitor
calyculin A significantly reduced Glu responses. It was suggested that the Glu
responsiveness of Purkinje cells may be regulated by the dynamic balance of
phosphorylation and dephosphorylation of receptors or other relevant factors
under basal conditions.
PMID- 9655613
TI - Talipexole protects dopaminergic neurons from methamphetamine toxicity in
C57BL/6N mouse.
AB - The effect of protection of dopaminergic neurons by talipexole, a dopamine (DA)
agonist, is investigated on a methamphetamine (MA)-induced parkinsonism model of
mice (C57BL/6N). The reduction of tyrosine hydroxylase activity in the striatum
72 h after MA (5 mg/kg every 2 h, four times) treatment was attenuated by the
administration of talipexole (0.25 mg/kg or 1.0 mg/kg) prior to the
administration of MA. In an in vitro experiment, talipexole inhibited the
adduction reaction of hydroxyl radicals to salicylate. Taken together, these data
suggest that the protective effect of talipexole on DA neurons is, in part,
caused by the hydroxyl radical-scavenging action of the drug.
PMID- 9655614
TI - Characterization of a plasma membrane zinc transporter in rat brain.
AB - Many studies now show that zinc plays a critical and unique role in central
nervous system development and function. The cellular mechanisms of zinc efflux
and influx are largely unknown and few models exist that describe cellular zinc
transport in the brain. This report provides convincing evidence of a zinc
transporter in plasma membrane vesicles isolated from rat brain. Zinc uptake was
saturable (Km = 15 microM; Vmax = 10 nmol/mg per 30 s), was seen in the absence
of ATP, and was unaffected by gradients for other ions such as Na+ or K+.
Increasing the ionic strength of the extravesicular media with Na+, K+, or
choline+ reduced zinc uptake approximately 50%. Whereas, increasing
extravesicular H+ concentration (pH = 5) resulted in near complete inhibition of
zinc uptake. Intravesicular zinc was rapidly released upon lowering
extravesicular concentrations of zinc with the heavy metal chelator O
phenanthroline (1 mM). The results are consistent with a freely-reversible
transport of zinc across the plasma membrane of neurons.
PMID- 9655615
TI - Spontaneous regeneration of the pyramidal tract after transection in young rats.
AB - Spontaneous regeneration of the pyramidal tract after transection of the
medullary pyramid was examined in young rats by the anterograde tracing method
with wheat germ agglutinin-conjugated horseradish peroxidase. Care was taken to
cut the tract as sharply as possible to minimize traumatic injuries. A very sharp
cut produced edema-free lesions without subsequent formation of either cysts or
scars, whereas a relatively blunt cut produced edema and later scars and/or cysts
in the lesion. Regenerated projections in the latter cases were sparse, short,
dispersed and largely aberrant as described in previous reports. By contrast,
regenerated projections in the former cases were very much similar to normal in
various respects: the amount, extension, path, formation of a compact bundle and
termination. There was, however, a decisive difference from normal, that is, the
additional aberrant projections.
PMID- 9655616
TI - Low and high frequency electroacupuncture at Hoku elicits a distinct mechanism to
activate sympathetic nervous system in anesthetized rats.
AB - To address the effect of electroacupuncture (Ea) on autonomic nerve activity, the
responses of rhythmic micturition contraction (RMC), urine excretion (UE), blood
pressure (BP), renal sympathetic nerve activity (RNA) and pelvic parasympathetic
nerve activity (PNA) to Ea were investigated in urethane-anesthetized rats. The
acupoint Hoku (Li-4) was tested with two different stimulation frequencies (2 Hz
and 20 Hz). Elongation of the RMC cycle and an increase in UE associated with the
elevation of BP and RNA was elicited during Ea at Hoku. However, the pressor
response induced by low frequency Ea (LFEa) was different from that by high
frequency Ea (HFEa), i.e. a tonic effect was elicited by LFEa, while a phasic one
was induced by HFEa. These results imply that: (1) Ea at Hoku may selectively
activate the sympathetic, but not the parasympathetic nervous system, (2) Ea at
Hoku with a different stimulation frequency may elicit a distinct mechanism to
activate the sympathetic nervous system and (3) Ea at Hoku may ameliorate the
hyperactive bladder in clinical therapy.
PMID- 9655617
TI - Colocalization of Bcl-2 and 4-hydroxynonenal modified proteins in microglial
cells and neurons of rat brain following transient focal ischemia.
AB - Bcl-2 has a role in suppressing the production of reactive oxygen species and
lipid peroxidation. To explore the in situ localization of 4-hydroxy-2-nonenal
(HNE)-modified proteins and the Bcl-2 oncoprotein, we used double
immunofluorescence labeling and confocal imaging in the rat brain after 3 h of
middle cerebral artery (MCA) occlusion followed by reperfusion. Immunoreactivity
for HNE or Bcl-2 was not detected at 1 h, but appeared in some intact neurons in
the boundary between the infarcted and non-infarcted zones at 12 h. At 48 h, HNE
positive microglia were colocalized with Bcl-2 in the infarcted area and the
boundary zone. Bcl-2 may play an important role in the antioxidant system
promoting survival of the neurons and activated microglia following reperfusion
injury.
PMID- 9655618
TI - Recoverin and hippocalcin distribution in the lamprey (Lampreta fluviatilis)
retina.
AB - Recoverin is a calcium-sensing protein which is involved in the transduction of
light in vertebrate photoreceptors. It is also detected in other retina cell
types in which its function is not yet elucidated, and is an autoantigen in a
cancer-associated degenerative disease of the retina. Recently, hippocalcin, an
homologous protein of recoverin, belonging to the same family of fatty acylated
EF-hand calcium binding proteins was described in mammals. The
immunohistochemical studies presented in this paper demonstrate, that, in the
retina of the lamprey, an Agnathan considered the living ancestor of actual jawed
vertebrates, recoverin was present in all photoreceptors and, to a lesser extent
in subpopulations of amacrine and ganglion cells whereas hippocalcin was detected
in numerous amacrine and ganglion cells and in the inner segments of long
photoreceptors. The existence of these calcium-binding proteins shows that they
have a high degree of conservation during evolution. Their presence in the same
cells that in jawed vertebrates (photoreceptors and ganglion cells for recoverin;
amacrine and ganglion cells for hippocalcin) suggests that some retinal functions
are well conserved but because they were also found in different cell types than
in other species (amacrine for recoverin; photoreceptors for hippocalcin), they
may have functions more specific to the lamprey retina.
PMID- 9655619
TI - Autoradiographic localisation of muscarinic cholinergic receptor subtypes in
human placenta.
AB - The localisation of M1-M4 muscarinic cholinergic receptor subtypes was
investigated in sections of normal human term placenta by light microscope
autoradiography. Muscarinic cholinergic receptor subtypes were found almost
exclusively in syncytiotrophoblast. Neither other cellular components of
placenta, nor blood vessels were labelled. Quantitative analysis of the density
of silver grains developed in sections incubated with the different protocols for
labelling M1-M4 receptor subtypes, revealed that syncytiotrophoblast expresses
all subtypes of muscarinic cholinergic receptor investigated. A higher density of
binding sites was found in the apical than in the basal portion of
syncytiotrophoblast. The demonstration of muscarinic cholinergic receptors in
syncytiotrophoblast suggests that a cholinergic system may have a role in
regulating transport of compounds from maternal to foetal interface.
PMID- 9655620
TI - Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome.
AB - Ts65Dn (TS), control littermates (CO) and Swiss (SW) male mice were tested in the
elevated plus-maze and in the Morris water maze (MWM) for memory evaluation. In
the plus-maze, each mouse was placed at the end of an open arm and initial
freezing and the time to enter into an enclosed arm (transfer latency) were
measured. SW mice decreased both measures over repeated trials, whereas no
decrease of freezing was observed in CO mice, thus suggesting increased
emotionality in this group. Compared to CO mice, TS mice showed less initial
freezing, shorter transfer latencies, and spent less time in enclosed arms,
suggesting a reduced ability to habituate or to inhibit behaviour. Animals were
also submitted to a learning-set paradigm consisting of reaching a new platform
position each day in the MWM. Two training phases (separated by a resting period
of 6 weeks), each including eight acquisition and four cued sessions, were
performed (each session consisting of four pairs of trials). CO and SW mice
already reached an asymptotic performance by the second day of the first phase
whereas TS mice did not achieve that level until the second training phase. The
progression over trials indicated that CO and SW animals learned the new platform
position between trials 1 and 2 of each session, whereas TS animals failed to do
it and had more difficulties to find the platform when it was placed in the
centre of the pool as compared to the other positions (SW, NE, E). The results
suggest that TS mice show working memory impairments in addition to long-term
memory deficits, although extensive training appeared to facilitate TS mice to
achieve a level of performance similar to their control littermates. This
represents another aspect of the cognitive deficits shown by TS mice: a mouse
model of the human Down syndrome.
PMID- 9655621
TI - Inwardly rectifying K+ currents in intermediate cells in the cochlea of gerbils:
a possible contribution to the endocochlear potential.
AB - The stria vascularis in the cochlea generates the endocochlear potential (EP) and
secretes K+-rich endolymph; both are indispensable for normal sound transduction
by hair cells. K+ conductance in the intermediate cell, one of the several types
of cells constituting the stria vascularis, was investigated by the whole-cell
patch-clamp technique. Inwardly-rectifying K+ (Kir) currents were the major
currents observed. The currents were inhibited dose-dependently by Ba2+, quinine,
verapamil and Cs+, but not by tetraethylammonium (20 mM), 4-aminopyridine (5 mM)
or Cd2+ (1 mM). The similarity between the effect of inhibitors on Kir currents
and on the EP (Takeuchi et al., Hearing Res., 101 (1996) 181-185) suggests a
direct contribution of the Kir conductance to the generation of the EP.
PMID- 9655622
TI - Cholinergic, but not the rod pathway-related glycinergic (All), amacrine cells
contain calretinin in the rat retina.
AB - Double-label immunocytochemistry was carried out on cryostat sections of rat
retina to test for the presence of calretinin in cholinergic starburst and the
rod pathway-related glycinergic (All) amacrine cells. All cholinergic cells
contained calretinin, but calretinin-immunoreactive cells were much more numerous
in both the inner nuclear and ganglion cell layers than the cholinergic cells.
Glycinergic All amacrine cells have been found to contain calretinin in cat,
monkey and rabbit retinas. Since All amacrine cells in rat can be selectively
labeled with antibodies against parvalbumin, in a second experiment we attempted
to colocalize these proteins. We found that calretinin- and parvalbumin
immunoreactive neurons belonged to distinct amacrine cell populations permitting
the conclusion that, in the rat retina, All amacrine cells do not contain
calretinin. The results indicate that even those amacrine cells of the mammalian
retina that are highly conserved with respect to morphology and transmitter
content, may differ with respect to other neurochemical characteristics, such as
their calcium-binding proteins.
PMID- 9655623
TI - Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic
rats is potentiated by simultaneous GABA(B) and adenosine receptor activation.
AB - In rats with abnormally low withdrawal thresholds ('allodynia') in one hindpaw
induced by a photochemical sciatic lesion, an intrathecal catheter was inserted
to the lumber enlargement and an epidural electrode was implanted at T11. I.t.
administration of GABA(B) or adenosine A1 receptor agonists (baclofen, R(-)-N6-(2
phenylisopropyl)adenosine (R-PIA)) suppressed allodynia in a dose-dependent
fashion. When the two agonists were given together, each in an ineffective dose,
there was a normalization of the thresholds. Rats, in which spinal cord
stimulation (SCS) could not suppress the allodynia (non-responders), were
transformed into SCS-responders by injection of baclofen and R-PIA in low,
ineffective doses, combined with SCS. In SCS responding rats, combination of a
selective GABA(B) and an adenosine A1 receptor antagonist (CGP 55845, CPT) in
low, ineffective doses abolished the SCS-induced threshold normalization. These
results indicate that GABAergic and adenosine-dependent mechanisms are involved
in the SCS effect and further suggest a strategy for enhancing the therapeutic
efficacy of SCS.
PMID- 9655624
TI - Does the cerebellum contribute to cognitive aspects of speech production? A
functional magnetic resonance imaging (fMRI) study in humans.
AB - Several positron emission tomography (PET) studies suggest a contribution of the
lateral aspects of the right cerebellar hemisphere to higher-level (cognitive)
aspects of speech production such as controlled verbal response selection. As an
alternative, however, 'inner speech', giving rise to subliminal activity of
orofacial and laryngeal muscles, might account for the observed activation
effects. Eighteen subjects underwent functional magnetic resonance imaging (fMRI)
during continuous silent recitation of the names of the months of the year
('automatic speech'). The right cerebellar hemisphere showed a significantly
increased hemodynamic response concomitant with, among others, an asymmetric
activation pattern towards the left side at the level of the motor strip. Since
highly overlearned word strings, presumably, pose few demands on controlled
response selection and since the projections of the right cerebellar hemisphere
to the left precentral gyrus participate in motor control, the observed
cerebellar activation, thus, seems to be related to the articulatory level of
speech production rather than, as suggested by previous PET studies, to cognitive
operations.
PMID- 9655625
TI - Changes in proton currents in murine microglia induced by cytoskeletal disruptive
agents.
AB - Voltage-gated proton currents (IPR) were investigated in cultured murine
microglia using the whole-cell configuration of the patch clamp technique. At a
gradient of 1.5 between intracellular (pHi = 6.0) and extracellular pH (pHo =
7.5) values, outward IPR were detected at depolarizing potentials, while the
activation threshold of IPR was -40 mV. Time-dependent activation of IPR was
fitted by a single exponential with a time constant of 661 ms at +40 mV. An
increase in the activation time constant of IPR was seen after exposure of
microglia to the cytoskeletal disruptive agents cytochalasin D or colchicine.
Moreover, the current density of IPR was significantly reduced by 49% in cells
treated with cytochalasin D and by 27% in cells treated with colchicine for 24 h.
In contrast, voltage-dependence of steady-state activation of IPR was unchanged
after disruption of the cytoskeleton. Exposure of microglia to the cytoskeletal
stabilizers phalloidin and taxol did not affect IPR of microglia.
PMID- 9655626
TI - Serum levels of macrophage-derived protein MRP-8/14 are elevated in active
multiple sclerosis.
AB - Serum concentrations of two macrophage-derived calcium-binding proteins, MRP-8
and MRP-8/14, were studied in 28 patients with relapsing multiple sclerosis (MS).
Serum levels were determined with a commercially available sandwich ELISA and the
one-tailed Mann-Whitney U test was used for statistical analysis. Median serum
levels of MRP-8/14 were significantly higher in MS patients (5150 ng/ml) compared
to 26 healthy controls (1482 ng/ml) and significantly higher in MS patients
within an acute relapse (6690 ng/ml) compared to MS patients with stable disease
(3050 ng/ml). MRP-8 levels were not elevated in MS patients. These results may
indicate an early activation of macrophages in the formation of demyelinating MS
plaques. In addition, increased serum levels of MRP-8/14 may prove to be a useful
paraclinical disease activity parameter in MS patients.
PMID- 9655627
TI - Cancellation of low-frequency stimulation-induced long-term depression by
docosahexaenoic acid in the rat hippocampus.
AB - The effects of docosahexaenoic acid (DHA) on low-frequency stimulation (LFS)
induced long-term depression (LTD) were investigated in the CA 1 subfield of rat
hippocampal slices. LTD was routinely produced by LFS of 900 pulses at 1 Hz. The
field excitatory postsynaptic potential (fEPSP) 40 min after LFS was 59 +/- 4% (n
= 18) of baseline response. However, in experiments from 18 neurons pretreated
with DHA (50 microM), fEPSP returned to baseline levels within 20 min after LFS
in eight cells and was slightly potentiated in three cells. Only in seven cells
was LTD induced. The effect of DHA on LTD was concentration dependent. The slopes
of fEPSP 40 min after LFS were 67 +/- 4% (n = 6), 72 +/- 7% (n = 7) and 80 +/- 5%
(n = 18) of baseline response, with pretreatment of 1, 10 and 50 microM DHA,
respectively. The blockade of LTD induction suggests that DHA may play a role in
learning and memory.
PMID- 9655628
TI - Comparison of mitochondrial respiratory chain enzyme activities in rodent
astrocytes and neurones and a human astrocytoma cell line.
AB - This study has found that mitochondrial NADH-CoQ1 reductase (complex I) activity
is significantly lower in C57 mice astrocytes compared with Wistar and Sprague
Dawley rat astrocytes, and a human astrocytoma cell line. In addition, complex I
activity is 4-fold greater in Sprague-Dawley neurones when compared to Wistar or
C57 neurones. These findings have important implications for mitochondrial
studies involving rodent or human cell line systems, and in particular, indicate
the importance of choosing an appropriate model when investigating the
mitochondrial respiratory chain.
PMID- 9655629
TI - Motor denervation induces altered muscle fibre type densities and atrophy in a
rat model of neuropathic pain.
AB - Loose ligation of a sciatic nerve in rats (chronic constriction injury; CCI)
provokes sensory, autonomic, and motor disturbances like those observed in humans
with partial peripheral nerve injury. So far, it is unknown whether these motor
disturbances result from (mechanical) allodynia or from damage to the motor
neuron. These considerations prompted us to assess, in CCI rats, the density of
motor axons in both the ligated sciatic nerve and the ipsilateral femoral nerve.
To this end, we determined the number of cholinesterase positive fibres. It has
been demonstrated previously that muscle fibre type density may be used as a
measure of motor denervation and/or hypokinesia. Therefore, the myofibrillar
ATPase reaction was employed to assess fibre type density in biopsies obtained
from the lateral gastrocnemius muscle (innervated by sciatic nerve) and rectus
femoris muscle (innervated by femoral nerve). We observed axonal degeneration of
motor fibres within the loosely ligated sciatic nerve, both at an intermediate
(day 21) and at a late stage (day 90) after nerve injury. The reduction in the
number of motor nerve fibres was more pronounced distal to the site of the
ligatures than proximal. A (less pronounced) reduction of motor fibres was
observed in the ipsilateral (non-ligated) femoral nerve. In line with these
findings, we observed altered fibre type densities in muscle tissue innervated by
the ligated sciatic nerve as well as the non-ligated femoral nerve indicative of
motor denervation rather than hypokinesia. The findings of this study suggest
that the motor disorder induced by partial nerve injury involves degeneration of
motor nerve fibres not only within the primarily affected nerve but also within
adjacent large peripheral nerves. This spread outside the territory of the
primarily affected nerve suggests degeneration of motor neurons at the level of
the central nervous system.
PMID- 9655630
TI - Dysphonia, an uncommon symptom of systemic neurotoxic envenomation by Vipera
aspis bite. Report of two cases.
AB - Two cases of Vipera aspis bites with severe envenomation in which, among other
neurotoxic signs, dysphonia was observed, with alteration of the pitch of the
voice are described. This uncommon symptom has never been reported in
envenomation by European adders. It is pointed out that bites of European vipers
should never be underestimated as severe envenomation may develop.
PMID- 9655631
TI - Gating and permeability of ion channels produced by botulinum toxin types A and E
in PC12 cell membranes.
AB - Botulinum neurotoxin (BoNT) is known to produce cationic channels in artificial
bilayers. This study examined ion channels formed by BoNT in native membranes
from cultured PC12 cells under conditions approximating those thought to occur
during toxin internalization. Membrane patches were excised from PC12 cells using
patch electrodes and exposed to symmetrical solutions containing either 200 mM
CsCl, RbCl or KCl. The patch pipettes also contained 1-5 microg/ml BoNT buffered
to pH 5.3 while the bath solutions were buffered to pH 7.0. In the presence of
toxin, bursts of ion channel openings were observed. These toxin-induced channels
were most active with a negative voltage applied to the same side as the toxin
(cis). The increased activity at negative voltages was due to an increase in mean
open time of e-fold per 120 mV and a decrease in mean closed time between bursts
of e-fold per 110 mV. The shorter mean closed time within a burst was independent
of membrane voltage. While BoNT-induced ion channels started as a single
conductance level of 27 pS (KCl), 34 pS (RbCl) or 46 pS (CsCl) they typically
increased in roughly equal steps to five or more times the original channel
conductance. These higher conductance BoNT 'channels' opened and closed
synchronously and could be distinguished from superposition of multiple
independent channels. Despite differences in putative transmembrane sequences
between BoNT/A and BoNT/E, both serotypes evidenced the same channel conductance
and mean open time.
PMID- 9655632
TI - Enkephalin-processing oligopeptidases in cobra venom: inhibition by thiorphan and
bestatin reveals co-operative actions.
AB - The peptidase inhibitors thiorphan and bestatin were tested for their ability to
inhibit the actions of the oligopeptidases contained in the venom of the Taiwan
cobra (Naja naja atra). With methionine enkephalin (TyrGlyGlyPheMet) as
substrate, thiorphan was an effective inhibitor of cleavage of the GlyPhe peptide
bond while bestatin inhibited cleavage of the TyrGly peptide bond. Thiorphan and
bestatin also inhibited subsequent cleavage of the fragments GlyGlyPheMet and
TyrGlyGly respectively. These inhibitors reveal an interplay between the venom
oligopeptidases in which the enzymes provide additional substrates for each other
following their initial competitive attack on the neuropeptide. A possible
explanation is that the system is intended to ensure a steady release of Tyr,
GlyGly and PheMet over time. Significantly, Tyr is the favoured substrate of the
L-amino acid oxidase present in the venom, which rapidly transforms this aromatic
amino acid into phenolic derivatives. The efficacies of these inhibitors also
suggest that there are similarities between the venom oligopeptidases and the
peptidases associated with the processing of enkephalin in its normal contexts.
PMID- 9655633
TI - A case of intestinal infarction following Vipera aspis bite.
AB - A case of Vipera aspis bite followed by severe envenomation, shock, neurotoxic
symptoms, myoglobinuria and coagulation disorders with thrombosis of the iliac
vessels and intestinal infarction is described. A right hemicolectomy had to be
performed. Treatment is described in detail. European adder bites may cause,
although uncommonly, severe envenoming with unusual symptoms. The attending
doctor must be prepared to face unusual diagnostic and therapeutic problems.
PMID- 9655634
TI - Differential neurotoxicity of etorphine-like opiates: lack of correlation with
their ability to activate opiate receptors.
AB - The present study was undertaken to compare the neurotoxic effects of three
etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of
oripavine) and heroin with their ability to activate opiate receptors in human
neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines.
Neurotoxicity was measured by using [3H]-thymidine incorporation analysis, cell
viability measurement and Cytosensor microphysiometry. It was found that, in
spite of the very similar molecular structures of these opiates, they displayed
significant differences in cytotoxicity, with etorphine and another derivative of
oripavine possessing high potency but dihydroetorphine and heroin little effect.
However, neurotoxic potency of the opiates was not directly correlated to their
ability to activate opioid receptors, as determined by [35S]-guanylyl-5'-O-(gamma
tho)-triphosphate binding assay. These findings provide clear evidence of
differential neurotoxicity of etorphine-like opiates, and suggest that the
neurotoxicity is not closely related to the molecular configuration required as
opioid receptor agonist but is probably associated with the presence of a double
bond in the structure.
PMID- 9655635
TI - Purification from Bothrops lanceolatus (fer de lance) venom of a
fibrino(geno)lytic enzyme with esterolytic activity.
AB - Bothrops lanceolatus venom has high caseinolytic, phospholipasic, esterolytic and
hemorrhagic activities. In spite of having no coagulant effect on plasma, this
venom contains a thrombin-like enzyme. Using gel filtration and ion-exchange
chromatographies, we have purified an esterolytic fraction (F-II-1a) from this
venom with a protein yield of 4% and a 58% recovery in enzyme activity. SDS-PAGE
in the presence of beta-mercaptoethanol showed that the enzyme is a single chain
polypeptide with a MW=38,100. Immunodiffusion and immunoelectrophoresis of
fraction F-II-1a against serum from horses immunized with B. lanceolatus venom
and against rabbit antiserum prepared using fraction F-II-1a both showed a single
immunoprecipitin line. The Km and Vmax values for TAME hydrolysis were 0.85 mM
and 38.6 micromol/min/mg, respectively. The esterolytic activity was completely
inhibited by PMSF (10 mM) but not by EDTA (20 mM). Fraction F-II-1a hydrolyzed
the alpha and beta chains of fibrinogen. Degradation of the alpha chain occurred
within 10 min while that of the beta-chain was slower. The enzyme had no effect
on the gamma-chain even after 4 h of hydrolysis.
PMID- 9655636
TI - Two similar peptides from the venom of the scorpion Pandinus imperator, one
highly effective blocker and the other inactive on K+ channels.
AB - Two novel peptides, named Pi4 and Pi7, were purified from the venom of the
scorpion Pandinus imperator, and their primary structures were determined. These
peptides have 38 amino acids residues, compacted by four disulfide bridges,
instead of the normal three found in most K+-channel specific toxins. Both
peptides contain 25 identical amino acid residues in equivalent positions (about
66% identity), including all eight half-cystines. Despite the fact that their C
terminal sequence comprising amino acid residues 27 to 37 are highly conserved
(10 out of 11 amino acids are identical), Pi4 blocks completely and reversibly
Shaker B K+ -channels (a Kv1.1 sub-family type of channel) at 100nM
concentration, whereas Pi7 is absolutely inactive at this concentration. Similar
effects were observed in binding and displacement experiments to rat brain
synaptosomal membranes using 125I-Noxiustoxin, a well known K+-channel specific
toxin. In this preparation Pi4 displaces the binding of radiolabeled Noxiustoxin
with Ic50 in the order of 10 nM, whereas Pi7 is ineffective at same
concentration. Comparative analysis of Pi4 and Pi7 sequences with those obtained
by site directed mutagenesis of Charybdotoxin, another very well studied K
channel blocking toxin, shows that the substitution of lysine (in Pi4) for
arginine (in Pi7) at position 26, might be one of the important 'point mutations'
responsible for such impressive variation in blocking properties of both toxins,
here described.
PMID- 9655637
TI - Pharmacological aspects of mouse hind-paw oedema induced by Lachesis muta
rhombeata venom.
AB - Pharmacological aspects of mouse hind-paw oedema induced by subplantar injections
of Lachesis muta rhombeata (LMR) venom were investigated. The oedema induced by
subplantar injections of 10 to 50 ng/g of LMR venom is dose dependent, with
onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar
injection of 30 ng/g of Bothrops jararaca (BJ) venom induced oedema that has the
same intensity as 30 ng/g of LMR venom but lasts for more than 4 h suggesting
different time course. Systemic effects or haemorrhage were not observed with
doses less than 50 ng/g. Oedema is not due to the presence of oedematogenic
amines since dialysis did not change the oedema induced by 30 ng/g of LMR venom.
Part of the oedema induced by LMR venom is due to a thermolabile fraction since
pre-heating the venom at 100 degrees C for 15 min induced a significant reduction
(56.19 +/- 6.8%) of the oedematogenic activity. The oedema induced by LMR venom
is possibly induced by release of a pharmacological active substance at the site
of injection. Histamine, arachidonate metabolites, nitric oxide and serotonin may
play important roles in the oedematogenic effect of LMR venom since pre-treatment
of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and methysergide
induced a significant reduction (49.86 +/- 10%; 51.06 +/- 5.9%; 77.66 +/- 3.6%;
73.30 +/- 6.1% and 93.77 +/- 2.8%, respectively) of the oedema formation. The
present results demonstrate that the oedema induced by LMR and BJ venoms may be
triggered and maintained by different pharmacological mechanisms. Since
methysergide and L-NAME were the most active inhibitors of the oedema we can
suggest that a link between serotonin release by the venom and a NO synthase
activation may be an important step in the oedema formation induced by LMR venom.
PMID- 9655638
TI - Purification of haemorrhagic proteinase from the venom of Agkistrodon caliginosus
(Kankoku-Mamushi).
AB - A haemorrhagic proteinase was purified from A. caliginosus venom by ion-exchange
chromatography on CM-Sephadex C-50, DEAE-Sephadex A-50, S-Sepharose Fast Flow and
Q-Sepharose Fast Flow, and gel-filtration on a Sephadex G-100 column. By this
procedure, about 17.6 mg of the enzyme were obtained from 4 g of the venom. The
enzyme showed a single band on polyacrylamide gel electrophoresis at pH 8.3 and
sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme had weak
caseinolytic and potent haemorrhagic activities, and the minimum haemorrhagic
dose of the enzyme was about 0.04 microg. The haemorrhagic activity of the enzyme
was only suppressed by treatment with ethylenediamine tetraacetic acid-disodium
or o-phenanthroline. The enzyme is composed of a single polypeptide chain with a
molecular weight of about 70 kDa and is a glycoprotein. These results indicate
that the enzyme is a metalloproteinase as are haemorrhagic proteinases from other
snake venoms.
PMID- 9655639
TI - Enzyme and biochemical studies of stonefish (Synanceja trachynis) and soldierfish
(Gymnapistes marmoratus) venoms.
AB - Venoms from the scorpaeniformes Synanceja trachynis and Gymnapistes marmoratus
were quantitatively analyzed for enzymic activity. S. trachynis venom displayed
significantly higher hyaluronidase activity than G. marmoratus venom, and G.
marmoratus venom displayed significantly higher levels of esterase, acid
phosphatase, alkaline phosphatase and phosphodiesterase activity. No detectable
quantities of phospholipase A2 activity were found in G. marmoratus venom. SDS
polyacrylamide gel electrophoresis of S. trachynis venom indicated the presence
of 6 protein bands (20 kDa-295 kDa). G. marmoratus venom displayed 8 protein
bands (11 kDa-109 kDa).
PMID- 9655640
TI - Tigloylcholine: a new choline ester toxin from the hypobranchial gland of two
species of muricid gastropods (Thais clavigera and Thais bronni).
AB - Crude extracts from hypobranchial glands of two species of muricid gastropods,
Thais clavigera and Thais bronni, were highly lethal to mice. Regardless of
species, a new choline ester was isolated as the major toxic principle and
elucidated to be tigloylcholine, a structural isomer of senecioylcholine widely
found in gastropod hypobranchial glands, by 1H- and 13C-NMR as well as FAB-MS.
The i.v. LD50 (mouse) of tigloylcholine was estimated to be 0.92 mg/kg.
PMID- 9655641
TI - Paralytic toxins in Taiwanese starfish Astropecten scoparius.
AB - Paralytic toxicity was seasonally detected in every 10 specimens of the starfish
Astropecten scoparius from Pingtung in Taiwan from December 1995 to November
1996. The highest toxicity and the average toxicity of total specimens, expressed
as tetrodotoxin (TTX), were 5,938 and 1,679 mouse unit (MU), respectively. The
highest value of monthly average toxicity in viscera and other parts were 354 and
247 MU/g, respectively. The toxin was partially purified by YM-2 membrane
ultrafiltration and Bio-Gel P-2 column chromatography. HPLC and GC-MS analyses
showed that the starfish toxin was mainly composed of tetrodotoxin (88%), along
with minor gonyautoxin 2-3 and saxitoxin (12%).
PMID- 9655642
TI - Tourniquet ineffectiveness to reduce the severity of envenoming after Crotalus
durissus snake bite in Belo Horizonte, Minas Gerais, Brazil.
AB - Clinical and laboratory data from patients who applied a tourniquet (tourniquet
group, n = 45) and who did not apply it (non-tourniquet group, n = 52) after
being bitten by Crotalus durissus were compared. The patients were treated with
100-200 ml of Crotalus durissus antivenom. The gender, age, time elapsed between
bite and hospital admission, dose of antivenom and the frequency of local
paresthesia, myalgia and palpebral ptosis did not differ between the two groups.
Plasma creatine kinase enzyme activity and partial thromboplastin time, plasma
whole venom and crotoxin concentrations and the frequency of acute renal and
respiratory failure and number of deaths also did not differ between both groups.
Data from this study show the ineffectiveness of tourniquet applied by patients
in the fields to reduce the severity of Crotalus durissus envenoming.
PMID- 9655643
TI - Envenomation of mice by Thai cobra (Naja kaouthia) venom: tolerable venom
concentration and exposure time.
AB - Naja kaouthia venom appeared in circulation rapidly after intramuscular injection
into mice. The venom concentration attained a maximum level with all doses
examined after 20 min. The half value of the maximum level was obtained 1 min
after injection when a dose of 4LD50 was used. A critical venom concentration
endangering mice was assessed from venom concentration in the sera of mice
envenomed with sublethal dose (LD50). A fatal condition was produced within 30
min at a venom concentration of 200-300 ng/ml or within 50 min at a venom
concentration of 100-150 ng/ml.
PMID- 9655644
TI - Influence of gossypol on the secretory function of cultured rat sertoli cells.
AB - Cottonseed gossypol is a potent male contraceptive in several mammalian species
including man. Sertoli cells play a crucial role in spermatogenesis. Therefore,
the antifertility competence of gossypol may reflect a change in Sertoli cell
function. Rat primary cultures were used to examine the effect of gossypol on
cell viability, mitochondrial dehydrogenase function, lactate production and
secretion of the Sertoli cell-specific protein inhibin. Exposure for 24 h to
gossypol (3-6 microM) significantly enhance secretion of lactate but reduce
secretion of inhibin without affecting cell viability. At 9-15 microM, the
observed decrease of both lactate and inhibin accumulation apparently resulted
from Sertoli cell degeneration and death, because viability and mitochondrial
function were also reduced. The results suggest that mitochondria of Sertoli
cells are a possible target for gossypol-induced infertility.
PMID- 9655645
TI - Bibliography of toxinology.
PMID- 9655646
TI - Angiotensin II antagonists: efficacy, duration of action, comparison with other
drugs.
AB - The benefits of anti-hypertensive drug treatment have been established by
clinical trials demonstrating significant reductions in cardiovascular morbidity
and mortality. Thiazide diuretics predominated in these trials but it is
reasonable to conclude that the benefits were attributable to the blood pressure
(BP) reduction per se and not to specific pharmacological characteristics.
Furthermore, it can be calculated that even greater benefits would probably have
accrued if the magnitude of the BP reduction had been greater. On first
principles, therefore, the basic requirement for any anti-hypertensive drug is
confirmation of its ability to reduce BP. The angiotensin II antagonists
constitute an important new class of drug, with a low incidence of adverse
effects, but early studies with the prototype, losartan, have raised some doubts
about its anti-hypertensive 'potency' in the clinical setting. For example, in
several different comparative studies there were consistently lesser BP
reductions with losartan compared to enalapril. This applied to both the trough
and peak BP reductions. Furthermore, dose-response relationships have not always
been clearly defined: for example, in one study diastolic BP reductions (trough)
fell in the range 4.1 to 4.8 mm Hg with 50, 100 and 150 mg losartan. Although the
preliminary results with newer angiotensin II antagonists suggest that they may
have greater efficacy, there is only limited information about the definitive
identification of the clinically relevant dose ranges for many of these drugs.
PMID- 9655647
TI - Molecular and cellular mechanisms of action of angiotensin II (AT1) receptors in
vascular smooth muscle.
AB - Angiotensin is an important regulator of blood pressure and exerts both pressor
actions and influences growth in the cardiovascular system via the AT1 receptor.
This review describes a number of signalling mechanisms involved in
vasoconstriction and growth in response to AT1 receptor activation in vascular
smooth muscle.
PMID- 9655648
TI - The potential role of angiotensin II in the vasculature.
AB - Arterial hypertension is associated with marked changes in the structure of both
resistance and large arteries. The renin-angiotensin system is largely involved
in these alterations; chronic blockade of the renin-angiotensin system prevents
and/or reverses most of the alterations of the vasculature in experimental and
clinical hypertension. In this review we have analysed the differential role of
AT1 and AT2 receptors in the response of the vessels to arterial hypertension. It
emerges that the relative involvement of each receptor depends on cell type, the
studied specie, and experimental condition. Several points must be investigated
in the near future, and especially: (1) the precise role of angiotensin receptors
in different cell types and different stages of differentiation; (2)the
transduction pathway used by the AT2 receptor in different cell types; (3) the
possible interactions between the two receptor subtypes; and finally, (4) a
possible role of (a) new subtype(s) of angiotensin II receptor.
PMID- 9655649
TI - Bioactive angiotensin peptides.
AB - Angiotensin II is recognised as the principle active peptide of the renin
angiotensin system, exerting effects on fluid and electrolyte homeostasis, and
cardiovascular control including neural and long term trophic effects. However,
recent studies indicate that other angiotensin peptides such as angiotensin III,
angiotensin II (1-7) and angiotensin IV, may have specific actions.
Interestingly, recent work involving angiotensin IV demonstrates that this
peptide binds to specific receptors and may be involved in memory retention and
neuronal development. Furthermore, our demonstration that a globin fragment, LVV
haemorphin-7, binds with high affinity to the angiotensin IV binding site and is
abundant in the brain, indicates that this may represent a novel brain
neuropeptide system. It now appears, that the renin-angiotensin system is more
complex than previously thought and capable of generating multiple, active
peptides which elicit numerous diverse actions.
PMID- 9655650
TI - The importance of the renin-angiotensin system in cardiovascular disease.
AB - The renin-angiotensin system is central to the pathophysiology of a number of
cardiovascular disorders. Most obviously this is so with renin secreting tumours,
but the system is of central importance in other disorders such as scleroderma
renal crisis and most cases of malignant hypertension. Activation of the renin
angiotensin system in unilateral renal artery stenosis is pivotal to the
development of hypertension and the disturbances in electrolyte and volume
balance -- most particularly in the hyponatraemic-hypertensive syndrome.
Likewise, stimulation of the renin-angiotensin system is an important
contributor, amongst many other systems, to the pathophysiology of cardiac
failure. In diabetic nephropathy, the renin-angiotensin system is often
suppressed as gauged by circulating levels of renin, yet it appears to make an
important contribution to the progressive decline in renal function. Much less
clear is the role of the renin-angiotensin system in essential hypertension
insofar as it contributes to the level of blood pressure, to the development of
left ventricular hypertrophy, and in the evolution of complications such as
stroke and myocardial infarction. Blockade of the renin-angiotensin system with
angiotensin-converting enzyme inhibitors has contributed to our understanding of
the role of this system in cardiovascular disease. The advent of selective
angiotensin II type-1 receptor blockers will further increase knowledge in this
area.
PMID- 9655651
TI - Angiotensin AT1 receptor antagonism and protection against cardiovascular end
organ damage.
AB - This review describes how angiotensin AT1 receptor antagonists (eg, candesartan
cilexetil, losartan) effectively protect against end-organ damage including
stroke, cardiac hypertrophy, renal dysfunction, glomerulosclerosis, and/or
vascular hypertrophy in the models of stroke-prone spontaneously hypertensive
rats (SHRSP), SHR, DOCA/salt hypertensive rats, Dahl hypertensive rats and/or 5/6
nephrectomised rats. Particularly in SHRSP and DOCA/salt hypertensive rats,
candesartan cilexetil markedly reduced the incidence of stroke and renal injury
even at doses which had no effect on blood pressure (BP), suggesting that the
tissue protective effects of angiotensin AT1 antagonists are not attributable
simply to the normalisation of BP. In the heart, kidney and vascular tissues of
SHRSP and the kidney of DOCA/salt hypertensive rats, the mRNA levels for
transforming growth factor (TGF)-beta1 and extracellular matrix components
(fibronectin, collagen type I, III and IV and laminin) were increased, and the
increases of the gene expression were inhibited by treatment with candesartan
cilexetil. In addition, there are some reports indicating that angiotensin AT1
receptor antagonists inhibit directly hypertrophy or proliferation of cultured
cardiac myocytes and nonmyocytes (fibroblast), cultured mesangial cells and
cultured vascular smooth muscle cells, which were stimulated by angiotensin II.
These in vitro and in vivo findings suggest that local tissue AT1 receptor
stimulation, being accompanied by the increased gene expression of TGF-beta1 and
extracellular matrix components may partially contribute to the pathogenesis of
cardiovascular end-organ damage.
PMID- 9655652
TI - Receptors and their classification: focus on angiotensin II and the AT2 receptor.
AB - Angiotensin II mediates its effects through angiotensin receptors. The use of
specific angiotensin receptor ligands and the cloning of these receptors allows
their classification. So far, the AT1, AT2 and atypical angiotensin II receptors
are recognised. The AT1 receptor is responsible for the classical effects of the
renin-angiotensin system such as vasoconstriction, renal salt and water
retention, central osmo-control and stimulation of cell growth. The function of
the AT2 receptor is far from clear but this receptor appears to be important in
fetal development, cell growth inhibition and differentiation processes. This
review describes the angiotensin receptors and focuses on the possible functions
of the AT2 receptor.
PMID- 9655653
TI - Postmenopausal hormone replacement therapy in hypertensive women: is it time for
a change in attitude?
PMID- 9655654
TI - Transdermal oestrogen reduces daytime blood pressure in hypertensive women [see
comment].
AB - The aim of this study was to investigate the acute effects of transdermally
administered 17-beta-oestradiol on ambulatory blood pressure (BP) in
hypertensive, postmenopausal women. Thirteen postmenopausal women with ongoing
treatment for hypertension were included in this placebo-controlled, double-blind
cross-over study. Ambulatory recordings of BP and heart rate were performed
during 24 h on two occasions, separated by at least 1 week, after application of
a patch containing either 100 microg per 24 h 17-beta-oestradiol or placebo.
Serum oestradiol was increased (P<0.001) during active treatment (139.2 +/- 21.1
pg/ml) compared with the baseline postmenopausal levels recorded during placebo
(40.5 +/- 2.2 pg/ml). No rise in BP was found in office BP or during ambulatory
recordings. Daytime BP pressure was acutely reduced by approximately 3 mm Hg
during the 24 h of treatment with oestrogen (SBP n.s., DBP P<0.05), without any
change in heart rate. Nocturnal dipping in SBP and DBP was present during placebo
conditions, and there were no signs of an increase in dipping during treatment
with 17-beta-oestradiol. This study supports previous evidence that hormone
replacement therapy is safe in hypertensive women. The data in the present study
also imply an acute, but small reduction of daytime BP due to transdermal
oestrogen in hypertensive, postmenopausal women. Furthermore oestrogen did not
blunt or increase the dipping phenomena during the night in these women.
PMID- 9655655
TI - Randomised comparison of percutaneous angioplasty vs continued medical therapy
for hypertensive patients with atheromatous renal artery stenosis. Scottish and
Newcastle Renal Artery Stenosis Collaborative Group.
AB - BACKGROUND: Data from randomised studies are lacking on the value of
interventional procedures in the management of atheromatous renal artery
stenosis. This randomised prospective trial compared the effects on blood
pressure (BP) and renal function of percutaneous transluminal angioplasty vs
medical therapy in hypertensive patients with both unilateral and bilateral
disease. METHODS: A total of 135 eligible patients were identified, of whom 55
(44%) were randomised. Eligible patients had sustained hypertension, with a
minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal
artery stenosis was defined by renal angiography as at least 50% stenosis in the
affected vessel. All patients were observed during an initial 4-week run-in
period on a fixed drug regimen and subsequent changes measured from this 4-week
baseline. RESULTS: Blood pressure fell during the run-in period in all groups. In
patients with bilateral renal artery stenosis randomised to angioplasty, a
statistically significant (P<0.05) fall in BP was observed at latest follow-up
(range 3-54 months). The mean fall in BP at latest follow-up in the angioplasty
group, corrected for the medical group response, was 26/10 mm Hg. In patients
with unilateral renal artery stenosis, no statistically significant or clinically
important differences in outcome were observed between the two groups. No
significant differences or trends in serum creatinine were observed between or
within any group during follow-up. Major outcome events (death, myocardial
infarction, heart failure, stroke, dialysis) were similar in the angioplasty and
medical groups during follow-up. In the 40/135 patients undergoing angioplasty,
serious or potentially serious complications attributable to the procedure were
observed in 11 patients, bleeding at the arterial site (8 patients) being the
most frequent. CONCLUSIONS: In hypertensive patients with atheromatous renal
artery stenosis, percutaneous renal angioplasty results in a modest improvement
in systolic BP compared with medical therapy alone. This benefit was confined to
patients with bilateral disease. No patient was 'cured', renal function did not
improve, and intervention was accompanied by a significant complication rate.
PMID- 9655656
TI - The prevalence of silent myocardial ischaemia in patients with white-coat
hypertension.
AB - The aim of this study was to estimate the incidence of silent myocardial
ischaemia in patients with mild to moderate hypertension, white-coat hypertension
(WCH) and those with normal blood pressure. Ambulatory electrocardiographic (ECG)
monitoring was carried out in 272 cases with normal blood pressure, 164 cases
with mild to moderate hypertension (diastolic blood pressure >95 and <114 mm Hg),
and 106 cases with white-coat hypertension who were diagnosed with ambulatory
blood pressure monitoring. The ages of the patients of all groups were between 42
61 years. There were no differences between the groups according to age, gender
and other parameters. There were no anginal symptoms, and resting ECGs were in
normal limits in all cases. The diagnosis of silent ischaemia was considered to
be present if there was ST depression >2 mm/at least 120 sec in ambulatory ECG
examination without angina or its equivalent cardiac symptoms. The incidence of
silent ischaemia was 6.4%, 18.8%, and 26.2% in cases with normal blood pressure,
WCH, and hypertension, respectively. The differences between groups were
significant. It was concluded that WCH is not a benign condition, but shares some
characteristics with essential hypertension.
PMID- 9655657
TI - Chest radiograph in the evaluation of first time wheezing episodes: review of
current clinical practice and efficacy.
AB - OBJECTIVE: To evaluate the current clinical use and utility of chest radiographs
(CXR) in the workup of pediatric patients with first time wheezing (FTW)
episodes. SETTING: Urban children's hospital. DESIGN: Retrospective review of
medical records of patients seen in the emergency department in 1994 with
disposition diagnoses of asthma or reactive airways disease, bronchiolitis,
pneumonia, congenital heart disease, congestive heart failure, or foreign body
aspiration to identify those patients presenting with FTW episodes. METHODS:
Clinical findings in FTW were compared in patients receiving a CXR (121, 41%) and
those who did not (177, 59%). Comparisons were made between patients with a
clinically significant CXR (CXR-pos) (29, 24%) and those without (92, 76%). CXR
pos was defined as a CXR result which would be expected to alter patient
management. Comparisons between groups were analyzed using the two-tailed
Student's t test for continuous variables and the chi2 statistic for categorical
data. The level of significance was determined at P < 0.05. RESULTS: Two hundred
ninety-eight episodes of FTW were identified of 1984 patient charts reviewed.
Patients receiving CXR differed from those who did not by being of a greater age
(39 vs 20 months, P < 0.01), having lower pulse oximetry (89.7 vs. 92.7%, P <
0.01), being less likely to have a family history of asthma (47.5 vs 63.2%, P <
0.01), or history of atopy (40.6 vs 59.4%, P < 0.01). Those with localized
wheezes (59.4 vs 40.6% P < 0.01), localized rales (59.3 vs 40.7 % P < 0.01), and
localized decreased breath sounds (59.3 vs 40.7%, P = 0.01) were also more likely
to receive a CXR. Among patients receiving CXR, clinical characteristics
associated with CXR-pos were elevated temperature (37.9 vs 37.5 degrees C, P =
0.04), absence of family history of asthma 72.6 vs 27.4%, P < 0.01), and the
presence of localized wheezes (76.0 vs 24.0%, P = 0.02), or localized rales (76.0
vs 24.0%, P < 0.01). CONCLUSIONS: Clinicians in this setting do not routinely
obtain a CXR in patients with FTW episodes. Retrospective examination of
clinician practice revealed several clinical characteristics that were associated
with increased use of CXR in FTW. Increased utility of the CXR was associated
with patients having elevated temperature, an absence of a family history of
asthma, and localized wheezes or rales by ausculatory examination.
PMID- 9655658
TI - Clinical criteria for using radiography for children with acute knee injuries.
AB - OBJECTIVE: To evaluate clinical criteria for selective radiography for knee
injuries in children. DESIGN: Retrospective chart review. SETTING: Emergency
department (ED) of a children's hospital. PARTICIPANTS: All patients evaluated by
radiography for an isolated, acute knee injury during 12 months. Patients were
excluded for injuries: >1 week; isolated to superficial lacerations/abrasions;
with prior knee surgery; being reassessed. RESULTS: Two hundred fifty-four
patients (60% male; 12.7 years median age) were included. Twelve patients (4.7%)
sustained a fracture. Evaluated criteria were point tenderness, inability to bear
weight in the ED, and inability to flex the knee to 90 degrees. Point tenderness
was not statistically associated with fracture, P = 0.7. Inability to bear weight
in the ED (37% fracture rate, P = 0.001) and inability to flex to 90 degrees (52%
fracture rate, P < 0.001) were associated with the presence of fracture.[table in
text] Applying a rule combining nobearwt and noflex90 would decrease the number
of x-rays by 73%, with no missed fractures. CONCLUSIONS: Point tenderness was not
a good predictor of knee fracture in children. Using the clinical criteria to
select patients requiring knee radiography may greatly reduce the number of
unnecessary x-rays.
PMID- 9655659
TI - The childhood air gun: serious injuries and surgical interventions.
AB - OBJECTIVE: Increasingly powerful nonpowder firearms or air guns are frequently
given to children as toys. We undertook the present study to evaluate the
injuries caused by these firearms, based on the concern that they are capable of
inflicting serious trauma. DESIGN: Descriptive, retrospective chart review.
SETTING: Urban level I pediatric trauma center. PARTICIPANTS: The study included
all children with injuries secondary to air guns who were admitted between July
1988 and March 1995. MAIN OUTCOME MEASURES: Type of weapon, circumstances of
injury, anatomic location of injury, injury severity, surgeries performed,
morbidity. INTERVENTIONS: None. RESULTS: There were 42 admissions with a mean
hospital stay of seven days (range 1 to 136 days). The average age was 10 years
(range 1 to 23 years) with a median age of 11 years. There were 35 boys and 7
girls. Twenty-nine of the 42 injuries were caused by a family member or friend
and five were self-inflicted. The mean injury severity score was 8.3. While there
were no fatalities, 21 children (50%) underwent operative procedures for their
injuries. Ten of the injuries were potentially lethal, of which seven were due to
the "pump" action air gun. Sixteen patients had serious long-term disability as a
result of their injuries. CONCLUSION: Air guns can cause a variety of serious
injuries, often requiring operative intervention. The long-term morbidity from
some of these injuries is significant. Both parents and physicians should be
aware that nonpowder guns are not toys, but weapons capable of inflicting serious
trauma. The evaluation and treatment of air gun injuries should be similar to
that currently used for powder weapon injuries. Recommendations for evaluation
and treatment are made.
PMID- 9655660
TI - Use of Emergency Medical Service transport system in medical patients up to 36
months of age.
AB - OBJECTIVES: To determine the frequency of inappropriate transport by Emergency
Medical Service (EMS). DESIGN: A retrospective study. SUBJECTS: Patients up to 36
months of age with medical complaints transported by EMS to an urban pediatric
emergency department (ED). INTERVENTIONS: None. MEASUREMENTS: Arbitrary criteria
for appropriate use of EMS transport system were developed. The age, triage
status, number of previous uses of EMS, health insurance status, time of calls,
chief complaint, and clinical management of patients in the ED were determined.
The frequency of inappropriate use of EMS was determined and also the percentage
of patients up to 36 months of age who used EMS transport system on more than one
occasion. RESULTS: Charts of 341 patients were reviewed of which 126 patients
(37%) could have been transported by nonemergent vehicles according to our
arbitrary criteria. In addition 97 (28%) of these patients had used the EMS
transport system on at least one other occasion. CONCLUSIONS: EMS is utilized for
inappropriate transportation in approximately 37% of our pediatric patients less
than 36 months of age with medical complaints. In addition, 28% of these same
patients utilized the EMS system on more than one occasion. It would appear that
education of care providers in the appropriate use of EMS and use of alternate
means of transportation would make the system more efficient and productive.
PMID- 9655661
TI - Streptococcus pneumoniae bacteremia in children infected with HIV: presentation,
course, and outcome.
AB - OBJECTIVE: To examine the presentation, course, and outcome of pneumococcal
bacteremia in children infected with human immunodeficiency virus (HIV). METHODS:
A retrospective series of HIV-infected children less than 18 years of age with
Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was
evaluated. The main outcome measures included persistent bacteremia, the
development of a focal infection, and death. RESULTS: Seventy-two episodes of
pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes
were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In
patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or =
10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia,
age >3 years old was associated with a lower mean WBC count compared with
episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients
with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.)
were less likely than patients without antibiotic treatment to have persistent
bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient
with occult bacteremia died, progressed to clinical meningitis, or had other
sequelae. Two of fifty-four patients died as a result of their first episode of
invasive pneumococcal disease. Both patients who died had meningitis and appeared
ill on initial presentation. CONCLUSIONS: Neither a WBC count > or = 15,000 nor >
or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected
children. Empiric antibiotics are useful to decrease the risk of persistent
bacteremia. Children infected with HIV who have occult pneumococcal bacteremia
appear to do well with appropriate antibiotics. Patients who are afebrile and
well appearing on reevaluation may be safely treated as outpatients.
PMID- 9655663
TI - Infant with epistaxis and absent femoral pulses.
AB - Coarctation of the aorta is a congenital cardiac abnormality that can lead to
congestive heart failure in early infancy or can go undetected for many years. We
discuss the case of an infant who presented to our emergency department with
epistaxis and was found to have this lesion based on the physical examination.
The identification of this lesion before the onset of symptoms leads to improved
survival in these patients. A cardiac murmur and differential blood pressure
between upper and lower extremities are the most reliable physical findings for
identifying patients with coarctation of the aorta. Absent femoral pulses are a
hallmark of this lesion, but not a dependable finding.
PMID- 9655662
TI - Physicians' attire as perceived by young children and their parents: the myth of
the white coat syndrome.
AB - OBJECTIVE: To determine if young children have a preference regarding whether
physicians do or do not wear a white coat. METHODS: One hundred one children,
ages four to eight years, and their parents were recruited from the outpatient
setting of a pediatric referral center. Two pairs of photographs, the same man
with and without a white coat and the same woman with and without a white coat,
were shown to the children and their parents, and both were asked which of each
pair they would like to have as their or their child's doctor, respectively.
Parents filled out a questionnaire rating the appropriateness of various aspects
of a physician's attire and appearance. RESULTS: The children selected the person
in the white coat 69% of the time. The parents also selected the white coat more
often (66%). On the questionnaire parents identified a name tag as the most
appropriate item of dress followed by a white coat. A groomed mustache and
groomed beard were also rated favorably. Open-toed sandals, clogs, and shorts
were rated negatively, while parents were neutral with respect to hospital
greens, blouse and skirt or dress, and shirt and tie. CONCLUSIONS: Physicians may
wear a white coat without fear that they are negatively affecting their
relationship with their pediatric patients four to eight years of age. The
appropriateness of wearing a name tag is confirmed.
PMID- 9655664
TI - Acute valproate ingestion induces symptomatic methemoglobinemia.
AB - A wide variety of clinical outcomes have been described after acute valproate
ingestion. We report for the first time the development of symptomatic
methemoglobinemia after an acute ingestion of divalproex sodium (Depakote),
resulting in serum concentrations 10 times greater than the therapeutic range.
The methemoglobinemia was readily reversed with the administration of methylene
blue. Valproate elimination was enhanced by the continuous infusion of activated
charcoal. The patient recovered without permanent sequelae.
PMID- 9655665
TI - Magnet-backed earrings: not just for decoration.
PMID- 9655666
TI - Vaginal injury from a water slide in a premenarcheal patient.
AB - BACKGROUND: Water under high pressure can produce vaginal injury. Previous
reports suggest that postmenarcheal maturation and the presence of a vaginal
foreign body contributed to water slide injuries in women. METHODS: A case of a
vaginal injury from a water slide in a premenarcheal patient is presented. A
literature review of water-related vaginal injuries in adults and children
compares the mechanism of injury with that previously reported. RESULTS: The
patient underwent operative repair of her injury. CONCLUSIONS: Vaginal injury in
premenarcheal patients may result from a water slide. The emergency physician
must be aware of this potential injury mechanism and the need for complete
examination under anesthesia when vaginal bleeding is present.
PMID- 9655667
TI - Acute hydrocephalus as a consequence of mumps meningoencephalitis.
AB - Aqueductal stenosis can result from mumps meningoencephalitis. We report a case
of acute hydrocephalus from an aqueductal stenosis developed immediately after a
clinically evident mumps infection. The patient, aged two years, was treated with
an antiedema therapy, and a ventriculoperitoneal shunt was placed. His clinical
conditions rapidly improved. Only mumps virus was found in his cerebrospinal
fluid culture. This case probably represents the earliest hydrocephalus from
mumps, among those reported in the literature.
PMID- 9655668
TI - Rickets presenting as seizures in the emergency department: medico-cultural
implications.
PMID- 9655669
TI - Reflex sympathetic dystrophy in children.
AB - Reflex sympathetic dystrophy is becoming increasingly recognized in the pediatric
population, yet there is very little about the disease in standard pediatric
texts and nothing in the emergency medicine literature. Failure to diagnose
Reflex sympathetic dystrophy in a timely fashion greatly decreases the likelihood
of recovery. The diagnosis is primarily clinical. This report is intended to
increase emergency physicians' awareness of this painful, disabling problem.
PMID- 9655670
TI - Use of restraints in ambulances: a state survey.
AB - PURPOSE: To determine the requirements in all states and the District of Columbia
for use of restraints on patients in ambulances. MATERIALS AND METHODS: A
structured telephone survey was conducted with all state Emergency Medical
Services (EMS) agencies or the agency responsible for the regulation of
ambulances. Questions were asked regarding restraint of patients in ambulances.
The age definition of a pediatric patient was also queried. RESULTS: Ambulances
are regulated in 47% of states by EMS, 14% by law enforcement, 3% by a public
safety agency, and in some states by other agencies such as the Department of
Motor Vehicles. In 27% of the states no agency is responsible for ambulance
regulations. Most states do not require patients of any age to be restrained in
ambulances; however, the drivers and passengers are required to wear seat belts.
Most of the states with laws regulating ambulance restraints for infants and
children were in the northeast. There is great variance in the age that defines a
pediatric patient for EMS. CONCLUSION: A means of safely restraining infants and
children in ambulances is needed. Until new restraints are available, ambulances
should restrain infants and children in car seats and on gurneys. A national age
standard for defining a pediatric patient using EMS is needed.
PMID- 9655671
TI - Toxicology reviews: physostigmine.
PMID- 9655672
TI - Four days of vomiting and diarrhea.
PMID- 9655673
TI - Management problems: what to do and when to do it.
PMID- 9655674
TI - Pediatric emergency medicine--legal briefs.
PMID- 9655675
TI - Just another asthmatic? The many faces of asthma in pediatric transport.
PMID- 9655676
TI - The use of propofol to treat status epilepticus in a nine-month-old female
patient.
PMID- 9655677
TI - G protein-coupled receptors in gastrointestinal physiology. IV. Neural regulation
of gastrointestinal smooth muscle.
AB - G protein-coupled receptors receive many of the neural, hormonal, and paracrine
inputs to gastrointestinal (GI) smooth muscle cells. This article examines the
major G protein-coupled receptors, G proteins, and effectors that mediate
responses to enteric neuromuscular transmitters. Excitatory transmitters
primarily couple through Gq/11 and Gi/Go proteins and elicit responses via
formation of inositol trisphosphate and diacylglycerol and inhibition of adenylyl
cyclase. Several inhibitory transmitters couple through Gs and activation of
adenylyl cyclase. There are interesting examples, however, of inhibitory
transmitters apparently using pathways regulated by Gq/11 to elicit responses by
localized Ca2+ release and activation of Ca2+-dependent ion channels. G protein
coupled receptors may also be differentially expressed by smooth muscle cells and
interstitial cells of Cajal, which may increase the diversity of responses and
allow specialized innervation of GI muscle tissues.
PMID- 9655678
TI - Neural injury, repair, and adaptation in the GI tract. II. The elusive action of
capsaicin on the vagus nerve.
AB - Capsaicin is an excitotoxin for primary afferent neurons, and perivagal
administration of capsaicin is frequently used to ablate afferent fibers from the
vagus nerve in an attempt to elucidate the role of afferent fibers in
gastrointestinal (GI) regulation. However, this method has recently been called
into question by research demonstrating that the molecular target of capsaicin on
spinal and trigeminal afferents, vanilloid receptor subtype 1 (VR1), is absent
from vagal afferents. Although some concerns about selectivity exist, the
available information suggests that perineural capsaicin defunctionalizes
afferent neurons of the vagus nerve by acting on a vanilloid receptor subtype
that is structurally different from VR1.
PMID- 9655679
TI - Changes in methionine adenosyltransferase during liver regeneration in the rat.
AB - Liver-specific and non-liver-specific methionine adenosyltransferase (MAT) are
products of two genes (MAT1A and MAT2A, respectively) that catalyze the formation
of S-adenosylmethionine (SAM), the principal methyl donor. We previously showed
that MAT2A expression was associated with more rapid cell growth. Here we
examined changes in hepatic MAT gene expression and related consequences after
two-thirds partial hepatectomy (PH) in rats. The mRNA levels of both MAT forms
increased from 3 to 6 h, but the MAT1A level then fell below baseline from 12 to
24 h, whereas the MAT2A level remained elevated up to 4 days after PH. The
increase in the MAT2A mRNA level was due to increased gene transcription and mRNA
stabilization. The change in the MAT1A mRNA level was posttranscriptional and did
not require de novo protein synthesis. Changes in MAT activity were consistent
with an increased amount of MAT isozymes. SAM levels, the ratio of SAM to S
adenosylhomocysteine (SAH), and DNA methylation fell from 6 to 24 h, whereas SAH
levels increased slightly at 12 and 24 h after PH. Both increased SAM utilization
and MAT2A gene expression likely contributed to the fall in SAM.
PMID- 9655680
TI - Secretin inhibits gastric acid secretion via a vagal afferent pathway in rats.
AB - Secretin is an enterogastrone that inhibits gastric acid secretion and motility.
Recently, it was reported that secretin inhibited gastric emptying via a
capsaicin (Cap)-sensitive vagal afferent pathway. However, a possible role of the
sensory afferent pathway in secretin-inhibited acid secretion has not been
clarified. We investigated whether or not the acid secretion suppressed by
secretin is modulated by a vagal and/or splanchnic afferent pathway in rats.
Subdiaphragmatic perivagal (PV) or periceliac ganglionic (PCG) application of Cap
(10 mg/ml) or vehicle was performed in both conscious and anesthetized rats 2 wk
before experiments. Bilateral vagotomy was performed in some conscious rats 5
days before studies. Pentagastrin was administered intravenously at 0.6 microg .
kg-1 . h-1. Secretin (20 pmol . kg-1 . h-1 iv) or 0.03 N HCl (4.32 ml/h id) was
infused in conscious rats with gastric cannulas or anesthetized rats with
ligation of the pylorus, respectively. A rabbit antisecretin serum was injected
in some anesthetized rats before duodenal acidification. Secretin significantly
inhibited pentagastrin-stimulated acid secretion by 63% (P < 0.01), which was
abolished by both vagotomy and PV treatment of Cap in conscious rats. In
anesthetized rats, duodenal infusion of 0.03 N HCl suppressed pentagastrin
induced acid secretion by 59.4% (P < 0.01), which was reversed not only by
antisecretin serum but also by PV application of Cap. However, PCG treatment with
Cap did not influence the inhibition by secretin or duodenal acidification in
either awake or anesthetized rats. These results indicate that the inhibition by
secretin of pentagastrin-stimulated acid secretion is mediated by a Cap-sensitive
vagal afferent pathway but not via a splanchnic afferent pathway in rats.
PMID- 9655681
TI - CD4+ T cells mediate superantigen-induced abnormalities in murine jejunal ion
transport.
AB - The immunomodulatory properties of bacterial superantigens (SAgs) have been
defined, yet comparatively little is known of how SAgs may affect enteric
physiology. Staphylococcus aureus enterotoxin B (SEB) was used to examine the
ability of SAgs to alter epithelial ion transport. BALB/c mice, severe combined
immunodeficient (SCID, lack T cells) mice, or SCID mice reconstituted with
lymphocytes or CD4+ T cells received SEB intraperitoneally, and jejunal segments
were examined in Ussing chambers; controls received saline only. Baseline short
circuit current (Isc, indicates net ion transport) and Isc responses evoked by
electrical nerve stimulation, histamine, carbachol, or forskolin were recorded.
Serum levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were
measured. SEB-treated BALB/c mice showed elevated serum IL-2 and IFN-gamma
levels, and jejunal segments displayed a time- and dose-dependent increase in
baseline Isc compared with controls. Conversely, evoked ion secretion was
selectively reduced in jejunum from SEB-treated mice. Elevated cytokine levels
and changes in jejunal Isc were not observed in SEB-treated SCID mice. In
contrast, SCID mice reconstituted with T cells were responsive to SEB challenge
as shown by increased cytokine production and altered jejunal Isc responses that
were similar to those observed in jejunum from SEB-treated BALB/c mice. We
conclude that exposure to a model bacterial SAg causes distinct changes in
epithelial physiology and that these events can be mediated by CD4+ T cells.
PMID- 9655682
TI - LPS receptor CD14 participates in release of TNF-alpha in RAW 264.7 and
peritoneal cells but not in kupffer cells.
AB - Lipopolysaccharide (LPS) is a bacterial polymer that stimulates macrophages to
release tumor necrosis factor-alpha (TNF-alpha). In macrophages (RAW 264.7 and
peritoneal cells), LPS binds to the CD14 surface receptor as the first step
toward signaling. Liver macrophages, Kupffer cells, are the most numerous fixed
tissue macrophage in the body. The presence of CD14 on Kupffer cells and its role
in LPS stimulation of TNF-alpha were examined. TNF-alpha release by Kupffer cells
after LPS stimulation was the same in the presence and absence of serum. RAW
264.7 and peritoneal cells, which utilize the CD14 receptor, released
significantly less TNF-alpha after LPS stimulation in the absence of serum
because of the absence of LPS-binding protein. Phosphatidylinositol-phospholipase
C treatment, which cleaves the CD14 receptor, decreased LPS-stimulated TNF-alpha
release by RAW 264.7 cells but not by Kupffer cells. Deacylated LPS (dLPS)
competes with LPS at the CD14 receptor when incubated in a ratio of 100:1
(dLPS/LPS). Such competition blocked LPS-stimulated TNF-alpha release from RAW
264.7 cells but not from Kupffer cells. Western and fluorescence-activated cell
sorter analysis directly demonstrated the presence of CD14 on RAW 264.7 cells and
murine peritoneal cells but showed only minimal amounts of CD14 in murine Kupffer
cells. LPS stimulation did not increase the amount of CD14 detectable on mouse
Kupffer cells. CD14 expression is very low in Kupffer cells, and LPS-stimulated
TNF-alpha release is independent of CD14 in these cells.
PMID- 9655683
TI - Altered sodium-hydrogen exchange activity is a mechanism for acid-induced
hyperproliferation in Barrett's esophagus.
AB - Acid produces a dynamic effect on the cell phenotype of Barrett's esophagus (BE)
ex vivo. An acid pulse induces hyperproliferation, whereas continuous acid
exposure promotes differentiation. To examine the mechanism for acid pulse
induced hyperproliferation, we studied the Na+/H+ exchanger (NHE), which plays a
role in the control of intracellular pH and cell proliferation. NHE was inhibited
pharmacologically in endoscopic BE biopsies using amiloride analogs. Cell
proliferation was assessed after pulsed or continuous acid exposure using
tritiated thymidine incorporation assays and immunohistochemical analysis of
proliferating cell nuclear antigen expression. The NHE-dependent intracellular pH
response to an acid pulse was examined by pH-sensitive microfluorimetry using a
Barrett's adenocarcinoma cell line TE7. NHE inhibition significantly reduced the
hyperproliferative acid-pulse effect. Furthermore, the acid-pulse activation of
NHE occurred via increased transporter activity (22Na uptake) without any change
in NHE-1 protein levels. Inhibition of protein kinase C (PKC), an NHE activator,
also reduced the hyperproliferative response. The response of TE7 cells to an
acid pulse was similar to that of BE biopsies in terms of cell proliferation and
NHE and PKC dependence. Acid-pulse exposure of TE7 cells resulted in
intracellular acidification followed by reneutralization to an intracellular pH
greater than preacidosis values. We conclude that NHE may mediate the
hyperproliferative response of BE to an acid pulse via changes in intracellular
pH.
PMID- 9655684
TI - Identification of a domain in the carboxy terminus of CCK receptor that affects
its intracellular trafficking.
AB - The carboxy-terminal region of many guanine nucleotide-binding protein (G
protein)-coupled receptors contains important regulatory sequences such as an
NP(x)2-3Y motif, a site of fatty acid acylation, and serine- and threonine-rich
domains. The type A CCK receptor contains all of these, yet their significance
has not been examined. We have, therefore, constructed a series of receptor site
mutants and truncations that interfere with each of these motifs and expressed
each in Chinese hamster ovary cells where they were studied for radioligand
binding, cell signaling, receptor internalization, and intracellular trafficking.
Each construct was synthesized and transported appropriately to the cell surface,
where CCK bound with high affinity, elicited an inositol 1,4, 5-trisphosphate
response, and resulted in internalization and normal trafficking. Thus
modification or elimination of each of these established sequence motifs had no
substantial effect on any of these parameters of receptor and cellular function.
However, an additional construct that truncated the carboxy terminus, eliminating
an additional 15-amino-acid segment devoid of any currently recognized sequence
motifs, resulted in a marked change in receptor trafficking, with all other
parameters of receptor function normal. This mutant receptor construct was
delayed at the stage of early endosomes, delaying its progress to the lysosome
enriched perinuclear compartment from the rapid time course followed by wild-type
receptor and all of the other constructs. It is proposed that this region of the
CCK receptor tail contains a new motif important for intracellular receptor
trafficking.
PMID- 9655685
TI - Mucosal mast cells are involved in CCK disruption of MMC in the rat intestine.
AB - Our aim was to determine if mucosal mast cells could be activated by endogenous
CCK and, as a consequence, mediate CCK actions in the small intestine. Rats were
prepared for electromyography to record electrical activity in the small
intestine. In another group of animals, the duodenum was perfused to measure rat
mast cell protease II (RMCP II) as indicative of mast cell degranulation.
Endogenous CCK release was induced by administration of soybean trypsin inhibitor
(SBTI) in conscious rats or by intraduodenal perfusion of ovalbumin hydrolysate
(OVH) in anesthetized rats. CCK concentration was measured by bioassay on
pancreatic acini. SBTI in control rats disrupted migrating motor complexes (MMC)
for >40 min. In rats treated with the mast cell stabilizer ketotifen, SBTI did
not induce any change in the MMC pattern. RMCP II concentration in the duodenal
perfusate significantly increased after OVH. Perfusate from ketotifen-treated
animals did not show any significant increase in RMCP II values during OVH
perfusion, although CCK plasma concentration was not different from the control
group. Furthermore, infusion of the CCK-B receptor antagonist L-365,260
significantly blocked the increase of RMCP II concentration after OVH. Our
results indicate that mucosal mast cells are degranulated by endogenous CCK
release through stimulation of CCK-B receptors. Therefore mucosal mast cells
participate in CCK intestinal actions.
PMID- 9655686
TI - Substance P receptor expression in intestinal epithelium in clostridium difficile
toxin A enteritis in rats.
AB - We previously reported that the inflammatory effects of Clostridium difficile
toxin A on rat intestine can be significantly inhibited with a specific
neurokinin-1 receptor (NK-1R) antagonist. In this study we investigated the
localization and expression of NK-1R mRNA and protein in rat intestine by in situ
hybridization, Northern blot analysis, and immunohistochemistry, respectively,
after exposure to toxin A. Northern blot analysis showed increased mucosal levels
of NK-1R mRNA starting 30 min after toxin A administration. In situ hybridization
showed that toxin A increased NK-1R mRNA expression in intestinal epithelial
cells after 30, 120, and 180 min. In rats pretreated with the NK-1R antagonist CP
96345 the increase in NK-1R mRNA levels after exposure to toxin A was inhibited,
indicating that NK-1R upregulation is substance P (SP) dependent. One hour after
exposure to toxin A many of the intestinal epithelial cells showed staining for
NK-1R compared with controls. Specific 125I-SP binding to purified epithelial
cell membranes obtained from ileum exposed to toxin A for 15 min was increased
twofold over control and persisted for 4 h. This report provides evidence that NK
1R expression is increased in the intestinal epithelium shortly after exposure to
toxin A and may be important in toxin A-induced inflammation.
PMID- 9655687
TI - Histamine stimulates ion transport by dog pancreatic duct epithelial cells
through H1 receptors.
AB - Histamine affects pancreatic secretion, but its direct action on ion transport by
pancreatic duct epithelial cells (PDEC) has not been defined. We now characterize
the secretory effects of histamine on cultured, well-differentiated, and
nontransformed dog PDEC. Histamine stimulated, in a concentration-dependent
manner (1-100 microM), a cellular 125I- efflux that was inhibited by 500 microM 5
nitro-2-(3-phenylpropylamino)benzoic acid, 2.5 mM diphenylamine-2-carboxylate,
and 500 microM DIDS and thus mediated through Ca2+-activated Cl- channels.
Histamine-stimulated 125I- efflux was 1) inhibited by 100 microM diphenhydramine,
an H1 receptor antagonist, 2) resistant to 1 mM cimetidine, an H2 receptor
antagonist, 3) not reproduced by 1 mM dimaprit, an H2 agonist, and 4) inhibited
by 50 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a Ca2+
chelator, suggesting that it was mediated through H1 receptors acting via
increased cytosolic Ca2+. Histamine also stimulated a 86Rb+ efflux that was
sensitive to 100 nM charybdotoxin and thus mediated through Ca2+-activated K+
channels. When PDEC monolayers were studied in Ussing chambers, a short-circuit
current of 21.7 +/- 3.1 microA/cm2 was stimulated by 100 microM histamine. This
effect was inhibited by diphenhydramine but not cimetidine, was not reproduced
with dimaprit, and was observed only after serosal addition of histamine,
suggesting that it was mediated by basolateral H1 receptors on PDEC. In
conclusion, histamine, acting through basolateral H1 receptors, activates both
Ca2+-activated Cl- and K+ channels; in this manner, it may regulate PDEC
secretion in normal or inflamed pancreas.
PMID- 9655688
TI - Short-chain fatty acids inhibit intestinal trefoil factor gene expression in
colon cancer cells.
AB - Intestinal trefoil factor (ITF) gene expression was detected in five colon cancer
cell lines. ITF was synthesized by mucous cells of LIM 1215 and LIM 1863 lines,
from which it is secreted constitutively. The ITF mRNA transcript was estimated
to be 0.6 kb. In LIM 1215 cells, the expression of ITF was potently and dose
dependently inhibited by short-chain fatty acids (butyrate > propionate >
acetate) within 8 h of application. The inhibitory effect of butyrate was ablated
by actinomycin D and preceded its effects on differentiation of LIM 1215 cells as
indicated by induction of alkaline phosphatase activity and counting of periodic
acid-Schiff-positive cells. The human ITF promoter contained an 11-residue
consensus sequence with high homology to the butyrate response element of the
cyclin D1 gene. Mobility shift assays show specific binding of this response
element to nuclear protein extracts of LIM 1215 cells. We conclude that butyrate
inhibits ITF expression in colon cancer cells and that this effect may be
mediated transcriptionally and independently of its effects on differentiation.
PMID- 9655689
TI - Interaction between neurokinin A, VIP, prostanoids, and enteric nerves in
regulation of duodenal function.
AB - Neurokinin A (NKA) induces duodenal motility and increases mucosal permeability
and bicarbonate secretion in the in situ perfused duodenum in anesthetized rats.
In the present study, the NKA-induced increase in mucosal permeability was
potentiated by luminal perfusion with lidocaine and diminished by vasoactive
intestinal peptide (VIP) but unaltered by elevated intraluminal pressure.
Elevation of intraluminal pressure, however, potentiated the stimulatory effect
of NKA on bicarbonate secretion. In contrast, the tachykinin decreased the rate
of alkalinization in rats subjected to elevated intraluminal pressure and treated
with indomethacin. Similarly, NKA partially inhibited the VIP-stimulated
bicarbonate secretion. Luminal lidocaine did not affect the secretory response to
NKA. The motility induced by NKA was unaffected by VIP or lidocaine but decreased
by elevated intraluminal pressure. It is concluded that the NKA-induced increase
in duodenal mucosal bicarbonate secretion is independent of neurons and possibly
mediated by prostanoids. The increase in mucosal permeability in response to NKA
may be suppressed by mucosal nerves, perhaps utilizing VIP as one of the
transmitters.
PMID- 9655690
TI - Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells.
AB - Extracellular triphosphate nucleotides, such as ATP, may regulate various
cellular functions through specific cell surface receptors. We examine in this
report the different secretory effects of ATP and analogs on nontransformed dog
pancreatic duct epithelial cells (PDEC). We observed that 1) ATP, UTP, adenosine
5'-O-(3-thiotriphosphate), and, to a lesser extent, beta, gamma-methylene-ATP,
but not adenosine, stimulated 125I- efflux from PDEC, suggesting a primary role
for P2Y2 receptors, 2) ATP-stimulated 125I- efflux was inhibited by 5-nitro-2-(3
phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and DIDS, suggesting
mediation through Ca2+-activated Cl- channels, 3) ATP stimulated an 86Rb+ efflux
sensitive to BaCl2 and charybdotoxin, thus likely occurring through Ca2+
activated K+ channels, 4) serosal or luminal addition of UTP activated apical Cl-
conductance and basolateral K+ conductance when nystatin-permeabilized PDEC were
studied in an Ussing chamber, suggesting the expression of P2Y2 receptors on both
sides of the cell, 5) ATP stimulated mucin secretion, and 6) ATP increases
intracellular Ca2+ concentration ([Ca2+]i). In conclusion, ATP and UTP interact
with P2Y2 receptors on nontransformed PDEC to increase [Ca2+]i, stimulate mucin
secretion, and activate ion conductances; these findings have implications for
pancreatic exocrine function in both health and disease, such as cystic fibrosis.
PMID- 9655691
TI - Characterization of rat epimorphin/syntaxin 2 expression suggests a role in crypt
villus morphogenesis.
AB - The rodent intestinal mucosa undergoes a remarkable morphogenesis as the crypt
villus axis is formed. Endoderm-mesenchymal interactions play a critical role in
this process. Epimorphin is a mesenchymal protein postulated to play a role in
lung and skin morphogenesis. The rat homologue, syntaxin 2, belongs to a family
of integral membrane proteins that function in vesicle docking and fusion. To
clarify its role in fetal gut morphogenesis, epimorphin expression was examined
during ontogeny, in an isograft model of ischemic injury and mucosal repair, and
during intestinal adaptation after small bowel resection. Epimorphin/syntaxin 2
mRNA levels were increased in fetal gut during lumen formation and villus
morphogenesis. mRNA levels remained elevated in the first 2 wk after birth and
then declined at weaning. In situ hybridization showed epimorphin/syntaxin 2 mRNA
in gestational day 14 (G14) and G15 intestinal mesenchymal cells and in the
mucosal lamina propria during villus formation. Epimorphin/syntaxin 2 mRNA
expression increased during villus repair in the isograft. In contrast, in the
early stages of intestinal adaptation after small bowel resection,
epimorphin/syntaxin 2 mRNA expression was suppressed in the adapting gut. We
conclude the cell-specific and temporal patterns of epimorphin expression in the
models used in this study suggest a role in the morphogenesis of the crypt-villus
axis.
PMID- 9655692
TI - S-adenosylmethionine deficiency and TNF-alpha in lipopolysaccharide-induced
hepatic injury.
AB - S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline.
Adomet deficiency occurs in certain types of liver injury, and the injury is
attenuated by exogenous Adomet. Tumor necrosis factor-alpha (TNF-alpha) is also a
mediator of these models of hepatotoxicity. We investigated the role of Adomet in
lipopolysaccharide (LPS)-induced liver injury in rats made deficient in both
Adomet and choline. Rats were maintained on either a methionine-restricted and
choline-deficient (MCD) diet or a diet containing sufficient amounts of all
nutrients [methionine and choline sufficient (MCS)] and then administered either
LPS or saline. MCS-LPS rats had normal liver histology and no change in serum
transaminases compared with the MCS-saline control group. MCD-saline rats had
hepatosteatosis but no necrosis, and a five- to sevenfold increase in
transaminases vs. the MCS-saline group. MCD-LPS rats additionally had
hepatonecrosis and a 30- to 50-fold increase in transaminases. Exogenous Adomet
administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not
of choline, prevented necrosis but not steatosis, and attenuated transaminases.
Serum TNF-alpha was sixfold higher in MCD rats even without LPS challenge and 300
fold higher with LPS challenge. Exogenous Adomet attenuated increased serum TNF
alpha in MCD-LPS rats.
PMID- 9655693
TI - Kinetics of particle uptake in the domes of Peyer's patches.
AB - Uptake of particulate antigenic matter, including microorganisms and vaccine
bearing microspheres, by the intestinal mucosa takes place in the domes of the
gut-associated lymphoid tissues and is achieved by membranous (M) cells, which
continuously transport particles from the lumen to the underlying tissue where
some particle components initiate immune reactions. Using yeast as tracer, we
investigated the kinetics of particle uptake in the Peyer's patches of pigs. A
suspension of baker's yeast (Saccharomyces cerevisiae) was injected into the gut
lumen of anesthetized minipigs; the position of yeast cells in the tissue was
determined after 1, 2.5, 4, and 24 h using fluorescence light- and thin-section
electron microscopy. After 1 h, 18.5% of all M cells had taken up or were in
close contact with yeast cells. The intercellular space of the epithelium
contained a maximum of 60.8% of all yeast cells found in the tissue after 2.5 h,
but only 1.3% had been phagocytosed by macrophages. After 4 h most yeast cells
(77.8%) were found beneath the basal lamina, and most of these (89%) were found
in macrophages. No yeast cells were detected in the Peyer's patch domes 24 h
after application. The data show that transcytosis of yeast particles (3.4 +/-
0.8 micron in diameter) by M cells takes <1 h. Without significant phagocytosis
by intraepithelial macrophages, the particles migrate down to and across the
basal lamina within 2.5-4 h, where they quickly get phagocytosed and transported
out of the Peyer's patch domes.
PMID- 9655694
TI - Origin of molecular species of diacylglycerol induced by bombesin in smooth
muscle cells from rabbit rectosigmoid.
AB - The source of early production of sn-1,2-diacylglycerol (DAG) has for a long time
been exclusively linked to hydrolysis of phosphatidylinositol 4,5-diphosphate,
which on receptor activation is hydrolyzed into DAG and inositol 1,4,5
trisphosphate. We have investigated the origin of lipid sources of DAG production
in smooth muscle cells, in response to contraction induced by peptide agonists.
We have performed a quantitative analysis of the molecular species of DAG formed
in relation to the known molecular composition of parent phospholipids. The
molecular species of phospholipids are sufficiently unique that the phospholipid
origin of DAGs and its quantitative contribution to their formation can be
measured by HPLC. Cell suspensions (10-15 x 10(6) cells/ml) from the circular
muscle of rabbit rectosigmoid were incubated in the presence of the contractile
peptide agonist bombesin (BB) at 10(-6) M. Reactions were stopped at different
time intervals from 30 s to 4 min. DAGs were extracted, purified by TLC, and
benzoylated with benzoic anhydride. The benzoylated DAGs were first purified by
TLC and then by normal phase HPLC before they were injected onto a reverse-phase
column and eluted isocratically. Furthermore, phospholipids in the lipid extract
[phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS),
and phosphatidylethanolamine (PE)] were purified by TLC and similarly analyzed
after hydrolysis to DAGs with phospholipase C (PLC). The DAG molecular species
profiles for PI, PC, PS, and PE were all unique. Contraction of cells with BB
gave noticeable increases (17-55%) in newly formed DAGs. The major phospholipid
source of the newly formed DAGs at 30 s was only approximately 30% from PI, and
the remainder was from PC. In contrast, after 4 min of BB stimulation, a decrease
was seen in newly formed DAGs in the peak specific for PI hydrolysis. The data
suggest that BB-induced contraction by activation of PLCs results in hydrolysis
of different phospholipids. The DAGs formed as a result are qualitatively and
quantitatively distinct. This could be the basis for the kinetically different
pattern of sustained contraction observed with BB.
PMID- 9655695
TI - IGF-I stimulates intestinal muscle cell growth by activating distinct PI 3-kinase
and MAP kinase pathways.
AB - Insulin-like growth factor I (IGF-I), acting via its cognate receptor, plays an
autocrine role in the regulation of growth of intestinal muscle cells. In the
present study the signaling pathways mediating the growth effects of IGF-I were
characterized in cultured human intestinal smooth muscle cells. Growth induced by
a maximally effective concentration of IGF-I (100 nM), measured as [3H]thymidine
incorporation, was only partially inhibited by LY-294002 [phosphatidylinositol 3
kinase (PI 3-kinase) inhibitor] or PD-98059 [mitogen-activated protein (MAP)
kinase kinase (MEK) inhibitor] (86 +/- 7% and 35 +/- 6% inhibition, respectively)
alone but was abolished by the two combined (114 +/- 18% inhibition), implying
the participation of both pathways. IGF-I elicited time- and concentration
dependent increases in PI 3-kinase activity. This effect was inhibited only by LY
294002 (89 +/- 12%). IGF-I elicited time- and concentration-dependent
phosphorylation of p44/p42 MAP kinase and increased MAP kinase activity. These
effects were inhibited only by PD-98059 (78 +/- 9% and 98 +/- 7%, respectively).
We conclude that in human intestinal muscle cells IGF-I activates distinct PI 3
kinase and MAP kinase signaling pathways, which act in conjunction to mediate
growth.
PMID- 9655696
TI - Involvement of intracellular Ca2+ stores in inhibitory effects of NO donor SIN-1
and cGMP.
AB - We investigated the role of K+ channels and intracellular Ca2+ stores in the
relaxations induced by the NO donor 3-morpholinosydnonimine (SIN-1) and 8-bromo
cGMP (8-BrcGMP), 8-(4-chlorophenylthio)-cGMP (pCPT-cGMP), and alpha, beta
methylene-ATP in isolated segments of rat ileum. The inhibitory responses to SIN
1 and the cGMP analogs were not influenced by the K+ blockers apamin,
charybdotoxin, iberiotoxin, or glibenclamide, whereas relaxations induced by
alpha,beta-methylene-ATP were abolished by apamin and tetraethylammonium. The NO
donor SIN-1 and the cGMP analogs were able to inhibit contractions induced by
activation of L-type Ca2+ channels (BAY-K-8644), by carbachol (CCh), and by
cyclopiazonic acid (CPA), a blocker of sarcoplasmic Ca2+-ATPase. However, the
inhibition of the combined CPA and CCh response was reduced and the dose-response
curve of SIN-1 shifted to the right. Intracellular Ca2+ stores were emptied by
incubation in Ca2+-free buffer and repetitive stimulation with CCh or BAY-K-8644.
After restoration of extracellular Ca2+, the inhibitory effect of SIN-1 and pCPT
cGMP was only attenuated, whereas in the additional presence of CPA, the
inhibitory effect of SIN-1 was blocked and the effect of 8-BrcGMP reduced. Thus
depleting intracellular Ca2+ stores attenuated the effect of SIN-1 and 8-BrcGMP,
suggesting an involvement of functional Ca2+ stores.
PMID- 9655697
TI - Gastric emptying flow curves separated from carbon-labeled octanoic acid breath
test results.
AB - Recently, we developed the [13/14C]octanoic acid breath test to measure gastric
emptying of solids. Although the method has been validated extensively,
absorption, metabolism, and excretion of the label in the breath need to be
corrected for. In this study a mathematical model was developed that allows for
1) separation of the global CO2 excretion after ingestion of the labeled test
meal into the emptying rate of the labeled test meal from mouth to pylorus and
the postgastric processing of absorption, metabolism, and excretion of the label,
and 2) numerical calculation of the half-emptying time and lag phase of the
emptied meal. The model was applied to the gastric emptying results obtained by
simultaneous scintigraphic and breath test measurements. An excellent correlation
was found between the gastric half-emptying time (r = 0.98) and lag phase (r =
0.85) determined scintigraphically and via breath test. There was also a good
agreement between the two methods [mean values and confidence limits for
differences: t1/2 = 10 min (-20 to 41) and tlag = -3 min (-39 to 34)]. Moreover,
the separated gastric emptying curves, lacking the influence of postgastric
processing of the label, showed real patterns of gastric outflow, which changes
from moment to moment.
PMID- 9655698
TI - Respiratory system mechanics in adult respiratory distress syndrome. Stretching
our understanding.
PMID- 9655699
TI - Acute respiratory distress syndrome caused by pulmonary and extrapulmonary
disease. Different syndromes?
AB - To assess the possible differences in respiratory mechanics between the acute
respiratory distress syndrome (ARDS) originating from pulmonary disease (ARDSp)
and that originating from extrapulmonary disease (ARDSexp) we measured the total
respiratory system (Est,rs), chest wall (Est,w) and lung (Est,L) elastance, the
intra-abdominal pressure (IAP), and the end-expiratory lung volume (EELV) at 0,
5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) in 12 patients with
ARDSp and nine with ARDSexp. At zero end-expiratory pressure (ZEEP), Est,rs and
EELV were similar in both groups of patients. The Est,L, however, was markedly
higher in the ARDSp group than in the ARDSexp group (20.2 +/- 5.4 versus 13.8 +/-
5.0 cm H2O/L, p < 0.05), whereas Est,w was abnormally increased in the ARDSexp
group (12.1 +/- 3.8 versus 5.2 +/- 1.9 cm H2O/L, p < 0.05). The IAP was higher in
ARDSexp than in ARDSp (22.2 +/- 6.0 versus 8.5 +/- 2.9 cm H2O, p < 0.01), and it
significantly correlated with Est,w (p < 0. 01). Increasing PEEP to 15 cm H2O
caused an increase of Est,rs in ARDSp (from 25.4 +/- 6.2 to 31.2 +/- 11.3 cm
H2O/L, p < 0.01) and a decrease in ARDSexp (from 25.9 +/- 5.4 to 21.4 +/- 55.5 cm
H2O/L, p < 0.01). The estimated recruitment at 15 cm H2O PEEP was -0.031 +/-
0.092 versus 0.293 +/- 0.241 L in ARDSp and ARDSexp, respectively (p < 0.01). The
different respiratory mechanics and response to PEEP observed are consistent with
a prevalence of consolidation in ARDSp as opposed to prevalent edema and alveolar
collapse in ARDSexp.
PMID- 9655700
TI - Lavage administration of dilute surfactants after acute lung injury in neonatal
piglets.
AB - Exogenous surfactant therapy is not standard in the acute respiratory distress
syndrome (ARDS) because of a lack of proven benefit. Nonuniform surfactant
distribution after either bolus or aerosol administration may be an important
factor limiting response. In a previous study of acute lung injury, we
demonstrated that lavage administration of Exosurf (13.5 mg phospholipid/ml) was
both effective and distributed uniformly in the lungs. Since the endogenous
surfactant pool is much smaller than the typical dose of exogenous surfactant
administered, we hypothesized that dilute surfactant preparations (4-4.5 mg
phospholipid/ml) administered by lung lavage would be equally effective in
reversing pulmonary dysfunction in a piglet model of acute lung injury. We
compared three dilute surfactants: Infasurf (n = 5), KL4-Surfactant (n = 6), and
Exosurf (n = 5) with controls (n = 6) and undiluted Exosurf (13. 5 mg
phospholipid/ml; n = 6). All dilute surfactant preparations were effective in
improving oxygenation and other parameters of pulmonary function. Surfactant
administered by lavage resulted in uniform lung distribution. We conclude that
dilute surfactants administered by lung lavage are effective in reversing
pulmonary dysfunction after acute lung injury. We speculate that doses in the
range of 20-40 mg phospholipid/kg may be adequate to improve lung function in
ARDS when exogenously administered surfactant is uniformly distributed in the
lung.
PMID- 9655701
TI - Automobile accidents in patients with sleep apnea syndrome. An epidemiological
and mechanistic study.
AB - To investigate the association between sleep apnea syndrome (SAS) and automobile
accidents, and to evaluate potential underlying mechanisms, we prospectively
recruited 60 consecutive patients with SAS (apnea-hypopnea index, 58 +/- 3 h-1)
and 60 healthy control subjects, matched for sex and age. The number of
automobile accidents during the past 3 yr was obtained from participants and
insurance companies. We quantified the degree of daytime sleepiness (Epworth
scale), anxiety and depression (Beck tests), and we assessed the level of
vigilance (PVT 192) and driving performance (Steer-Clear). Patients had more
accidents than control subjects (OR: 2.3; 95% CI: 0.97 to 5.33) and were more
likely to have had more than one accident (OR: 5.2; 95% CI: 1.07 to 25.29, p <
0.05). These differences persisted after stratification for km/yr, age, and
alcohol consumption. Patients were more somnolent, anxious, and depressed than
control subjects (p < 0.01), and they had a lower level of vigilance and poorer
driving performance (p < 0.01). Yet, we did not find any correlation between the
degree of daytime sleepiness, anxiety, depression, the number of respiratory
events, nocturnal hypoxemia, level of vigilance, or driving simulator performance
and the risk of automobile accidents among SAS patients. In conclusion, patients
with SAS have an increased risk of automobile accidents. None of the clinical or
physiological markers commonly used to define disease severity appear able to
discriminate those patients at higher risk of having an automobile accident.
PMID- 9655702
TI - The rise and dwell time for peak expiratory flow in patients with and without
airflow limitation.
AB - The response of peak expiratory flow (PEF) meters may be affected by the
magnitude of PEF, the time taken to get to PEF, and the duration that the peak is
sustained. We undertook a retrospective study to define the 10 to 90% rise time
(RT) and dwell time for flow above 90% (DT90) and 95% (DT95) of PEF. Blows were
analyzed that had been recorded using a pneumotachograph from 912 patients older
than 17 yr of age (556 men) who routinely attended a lung function laboratory.
For each subject, that blow with the largest PEF was used to derive the PEF,
FEV1, FVC, RT, DT90, and DT95. The values for RT, DT90, and DT95 were negatively
skewed with the median values for men of 58, 29, and 19 ms, respectively, being
significantly shorter than those for the women of 67, 49, and 31 ms. From the 912
subjects, there were 277 (153 men) who had all their spirometric indices within
the normal range, and 305 (220 men) had both PEF and FEV1 more than 1. 645 SD
below predicted, indicating airflow limitation. For subjects with airflow
limitation the median RT was significantly smaller than in the normal subjects
(men: 46 versus 72 ms, women: 50 versus 72 ms), and the same was found for DT90
(men: 22 versus 40 ms, women: 27 versus 56 ms) and DT95 (men: 15 versus 26 ms,
women: 18 versus 34 ms). We conclude that the dwell times for PEF are shorter in
men, and the rise and dwell times are shorter in patients with airflow
limitation. Profiles used to test PEF meters should encompass the range of rise
and dwell times found in subjects most likely to be using PEF meters, that is,
those with airflow limitation.
PMID- 9655703
TI - Additivity of protein and nonprotein inhibitors of lung surfactant activity.
AB - This study examined the degree of additivity of several physiologically relevant
protein and nonprotein inhibitors in impairing the surface activity of whole and
extracted calf lung surfactant (LS and CLSE) on a pulsating bubble apparatus at
37 degrees C. Inhibitors investigated were albumin, hemoglobin, C16:0 and C18:1
lysophosphatidylcholine (LPC), oleic acid (OA), palmitoleic acid (PA),
arachidonic acid (AA), and mixed red blood cell membrane lipids (RBCML). In the
absence of inhibitors, LS (0.5 mg/ml) and CLSE (0.75 mg/ml) reached minimum
surface tensions < 1 mN/m within 5 min of bubble pulsation (20 cycles/min, 50%
area compression). Each inhibitor acting alone was able to reduce the surface
activity of LS and CLSE, either raising minimum surface tension or increasing the
time course of surface tension lowering or both. Several combinations of
inhibitors exhibited additivity in impairing LS or CLSE activity at a lower
concentration in mixtures than when present alone (albumin plus either C16:0 LPC,
C18:1 LPC, or RBCML; hemoglobin plus either C16:0 LPC, C18:1 LPC, RBCML, PA, OA,
or AA). The degree of additivity, however, was typically small in terms of the
magnitude of reduction in inhibitor concentration or the rise in minimum surface
tension relative to the effects of the most severe single inhibitor present.
Substantial synergy was not found for any of the combinations of protein and
nonprotein inhibitors investigated. Mixtures of albumin with PA or AA actually
had a reduced inhibitory effect on LS and CLSE activity compared with the free
fatty acids alone, apparently because of albumin binding of these molecules. In
all cases, the detrimental effects of mixed inhibitors on LS and CLSE activity
were reversed at increased surfactant concentration. These results indicate that
surfactant dysfunction in acute respiratory distress syndrome (ARDS) could be
increased in severity by interactions between some inhibitory substances, but
that supplementation with exogenous CLSE would be effective in reversing
inactivation by the mixtures of blood proteins, membrane lipids, and fatty acids
studied.
PMID- 9655704
TI - Epidemiological association of airway inflammation with asthma symptoms and
airway hyperresponsiveness in childhood.
AB - The role of airway inflammation in childhood asthma is not well defined, despite
modern treatment approaches recommending potent anti-inflammatory therapy for an
increasing number of children. In this study, induced sputum analysis was used to
investigate the relationships among sputum inflammatory cells (eosinophils and
mast cells), asthma symptoms, and airway hyperresponsiveness to hypertonic saline
in a cohort of 170 children aged 8-14 years. Children who reported asthma
symptoms in the past 2 wk had a 2. 25-fold (95% to CI, 1.20-4.24) increased odds
of having significant sputum eosinophilia. Hyperresponsiveness to hypertonic
saline was strongly associated with higher levels of sputum eosinophils ([OR] 4.
36, 1.70-11.20), sputum mast cells (OR 7.46, 2.48-22.75), and nasal eosinophils
(OR 4.73, 1.89-11.86). Interestingly, boys were more likely than girls to have
features of airway inflammation (sputum mast cells, OR 3.33, 1.15-9.65; nasal
eosinophils, OR 3.25, 1.72-5. 97), which is consistent with the known increase in
asthma prevalence in boys in this age group. Airway inflammation with eosinophils
and mast cells is likely to be important in the pathogenesis of asthma in
childhood. Induced sputum analysis can be used to evaluate this problem and has
the potential to be a useful tool for monitoring therapy.
PMID- 9655705
TI - Involvement of tachykinin NK3 receptors in citric acid-induced cough and
bronchial responses in guinea pigs.
AB - Aerosolized citric acid induces several pulmonary effects including
bronchoconstriction, airway inflammation, and cough. Evidence from the use of
tachykinin NK1 and NK2 receptor antagonists, as well as chronic treatment with
high doses of capsaicin, have suggested that these effects are mediated through
the release of tachykinins from sensory nerve endings. In the present study, we
have investigated the effects of a tachykinin NK3 receptor antagonist, SR 142801
(osanetant), on cough, bronchoconstriction, and bronchial hyperresponsiveness
induced by aerosolized citric acid (0.4 M) in guinea pigs. SR 142801, at 0.3 and
1 mg . kg-1 by intraperitoneal route, significantly inhibited cough in conscious
guinea pigs by 57 +/- 3 and 62 +/- 10% (n = 8), respectively. In anaesthetized
guinea pigs, it failed to inhibit the bronchoconstriction induced by citric acid
when given alone but abolished it when combined with the tachykinin NK2 receptor
antagonist, SR 48968 (saredutant). In guinea pigs pretreated with thiorphan (1 mg
. kg-1), aerosolized citric acid (0.4 M, 1 h) induced airway hyperresponsiveness
24 h later, displayed by an exaggerated response to the bronchoconstrictor effect
of acetylcholine. A microvascular leakage hypersensitivity also occurred and was
demonstrated by a potentiation of the plasma protein extravasation from bronchial
vessels induced by histamine. When given once intraperitoneally at 1 mg . kg-1 30
min before the citric acid exposure, SR 142801 inhibited both hyperresponsiveness
to acetylcholine and the potentiation of histamine-induced increase in
microvascular permeability. The results suggest that tachykinin NK3 receptors are
involved in citric acid-induced effects on airways.
PMID- 9655706
TI - Survival and FEV1 decline in individuals with severe deficiency of alpha1
antitrypsin. The Alpha-1-Antitrypsin Deficiency Registry Study Group.
AB - Subjects >= 18 yr of age with serum alpha1-antitrypsin (alpha1-AT) levels <= 11
microM or a ZZ genotype were followed for 3.5 to 7 yr with spirometry
measurements every 6 to 12 mo as part of a National Heart, Lung, and Blood
Institute Registry of Patients with Severe Deficiency of Alpha-1-Antitrypsin.
Among all 1,129 enrollees, 5-yr mortality was 19% (95% CI: 16 to 21%). In
multivariate analyses of 1, 048 subjects who had been contacted >= 6 mo after
enrolling, age and baseline FEV1% predicted were significant predictors of
mortality. Results also showed that those subjects receiving augmentation therapy
had decreased mortality (risk ratio [RR] = 0.64, 95% CI: 0. 43 to 0.94, p = 0.02)
as compared with those not receiving therapy. Among 927 subjects with two or more
FEV1 measurements >= 1 yr apart, the mean FEV1 decline was 54 ml/yr, with more
rapid decline in males, those aged 30 to 44 yr, current smokers, those with FEV1
35 to 79% predicted, and those who ever had a bronchodilator response. Among all
subjects, FEV1 decline was not different between augmentation-therapy groups (p =
0.40). However, among subjects with a mean FEV1 35 to 49% predicted, FEV1 decline
was significantly slower for subjects receiving than for those not receiving
augmentation therapy (mean difference = 27 ml/yr, 95% CI: 3 to 51 ml/yr; p =
0.03). Because this was not a randomized trial, we cannot exclude the possibility
that these differences may have been due to other factors for which we could not
control.
PMID- 9655707
TI - Cotinine excretion as a predictor of peak flow variability.
AB - Environmental tobacco smoke (ETS) is suspected to be an important risk factor for
bronchial hyperresponsiveness. In order to test the effect of ETS, we measured
expiratory flow rates and urine cotinine excretion (UCE) within a narrow time
window in two consecutive years. Maternal smoking habits and medical history were
ascertained by standardized questionnaires. The percentage ratio of the amplitude
over the mean (AVAM) of the diurnal peak flow rates of children (complete values
from at least five consecutive days) was calculated as an indicator of bronchial
responsiveness. The association of UCE and log10AVAM was analyzed by multiple
linear regression. Complete data were available for a sample of 417 children. The
median of UCE in children of parents who smoked (3.2 ng/mg and 2.9 ng/mg
creatinine, Surveys 1 and 2, respectively) was higher than the median in children
of nonsmoking parents (0 ng/mg in both surveys). With increasing UCE the
log10AVAM rose in the first and second surveys, as well as in the longitudinal
analysis (p = 0.003). This association, however, showed up only in boys (p =
0.0001) and not in girls (p = 0.31). Our data suggest that there is a need both
for further analysis of the gender difference and for more support of strategies
against passive smoking as far as children are concerned, since airway
hyperresponsiveness is a risk factor for chronic airway impairment.
PMID- 9655708
TI - Evaluation of a new, rapid, and quantitative D-Dimer test in patients with
suspected pulmonary embolism.
AB - Previous studies have suggested the utility of D-Dimer ELISA assays in
eliminating a diagnosis of pulmonary embolism (PE). Our objectives were to
evaluate the performance of a new, rapid, quantitative, and automated Liatest D
Dimer Assay in patients with suspected PE. Three hundred eighty-six consecutive
patients referred to our institution between March 1992 and December 1996 for
clinically suspected PE, with recent clinical signs not exceeding 1 wk, were
included in this study. Diagnosis of PE was based on clinical evaluation,
radionuclide lung imaging, lower limb examination, and, when required, pulmonary
angiography. D-Dimer performances, for both Liatest D-Dimer and standard D-Dimer
ELISA (Asserachrom DDi), assays, were assessed at the end of the study. Among the
386 patients tested, 146 (37.8%) were classified as PE-positive. Liatest D-Dimer
assay had a 100% sensitivity (95% confidence interval, 97 to 100%) and a negative
predictive value of 100% (95% confidence interval, 94 to 100%). A normal result,
below the cutoff of 500 ng/ml, occurred in 83 of the 386 (21%) patients. There
was a strong agreement between Liatest D-Dimer and Asserachrom DDi analyses.
These findings suggest that this rapid, quantitative, and automated D-Dimer assay
provides a useful diagnostic tool for the clinician with regard to exclusion of
PE.
PMID- 9655709
TI - Lung volume reduction surgery has variable effects on blood gases in patients
with emphysema.
AB - Most studies of bilateral lung volume reduction surgery (LVRS) report increases
in arterial oxygenation (PaO2). Some suggest this results from an increased
alveolar ventilation, but others imply that ventilation-perfusion heterogeneity
is reduced. We measured arterial blood gases (ABGs) on air before and 3 mo
following LVRS in 46 patients (61% of eligible patients), estimate the difference
between alveolar and arterial O2 (AaPO2), and correlated the changes observed
with preoperative ABGs, and with pre-and postoperative pulmonary function. The
mean +/- SD change in PaO2 and AaPO2 was +3 +/- 10 mm Hg (p = 0.058) and +1 +/-
11 mm Hg (p = NS), respectively, and the range of change was large (-17 to +29 mm
Hg and -24 to +23 mm Hg, respectively). The mean change in PaCO2 was -3 +/- 5 mm
Hg (p < 0.05) and ranged from -11 to +5 mm Hg. Changes in PaO2 and AaPO2 were
poorly correlated with changes in PaCO2 or with pre- or postoperative pulmonary
function. Although some patients had a marked improvement in ABGs following LVRS,
almost as many deteriorated. On average, only minimal effects were seen. Although
mean alveolar ventilation improved somewhat, the effect of LVRS on PaO2 primarily
resulted from alterations in ventilation-perfusion heterogeneity.
PMID- 9655710
TI - Noninvasive monitoring of cardiac output in critically ill patients using
transesophageal Doppler.
AB - Measurement of cardiac output using thermodilution technique in mechanically
ventilated patients is associated with significant morbidity. The goal of the
present study was to assess the validity of cardiac output measurement using
transesophageal Doppler in critically ill patients. Forty-six patients from three
different intensive care units underwent 136 paired cardiac output measurements
using thermodilution (COTH) and transesophageal Doppler (COTED). In addition,
simultaneous suprasternal Doppler and indirect calorimetry (Fick principle) were
used to measure cardiac output in 26 patients from one center. A good correlation
was found between COTH and COTED (r = 0.95), with a small systematic
underestimation (bias = 0.24 L/min) using transesophageal Doppler. The limits of
agreement between COTH and COTED were +2 L/min and -1.5 L/min. Variations in
cardiac output between two consecutive measures using either transesophageal
Doppler or thermodilution techniques were similar in direction and magnitude
(bias = 0 L/min; limits of agreement = +/-1.7 L/min). Suprasternal Doppler and
indirect calorimetry yielded similar correlations and agreements in the subset of
patients in whom they were used. These results confirm that transesophageal
Doppler can provide a noninvasive, clinically useful estimate of cardiac output
and detect hemodynamic changes in mechanically ventilated, critically ill
patients.
PMID- 9655711
TI - Endobronchial biopsy and bronchoalveolar lavage in stable lung transplant
recipients and chronic rejection.
AB - We have obtained endobronchial biopsies (EBB), bronchoalveolar lavage (BAL), and
transbronchial biopsies (TBB) in 17 stable lung transplant recipients (sLTR), 8
subjects with physiologic evidence of chronic rejection (BOS), and 9 normal
subjects. A striking finding was the marked neutrophilia in BAL samples from
patients with BOS, in the carefully screened absence of infection. A
statistically higher neutrophil count was also present in the sLTR group relative
to the normal group. Median BAL neutrophil count in BOS was 100 x 10(3)/ml, range
13-1,661 10(3)/ml (p < 0.001 relative to normal subjects and sLTR). Median BAL
neutrophil count in sLTR was 7 x 10(3)/ml, range 1-81 10(3)/ml (p < 0.01 relative
to normal subjects). Normal subjects had a median BAL neutrophil count of 3 x
10(3)/ml, range 1-7 10(3)/ml. There was evidence of a predominance of CD8
lymphocytes in BAL from sLTR and BOS with a lower CD4/CD8 ratio in both compared
to normal subjects (p < 0.05). EBB mononuclear cell counts, class II major
histocompatibility complex expression, and T-cell activation markers were normal
in BOS, in contrast to the sLTR group. Our data may be consistent with BOS,
representing a relative resolution of an active mononuclear cell chronic
inflammation, perhaps at the expense of airway fibrosis. The relevance of the BAL
neutrophilia and its role in BOS pathogenesis need further longitudinal
investigation.
PMID- 9655712
TI - Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in
endotoxemic chimpanzees.
AB - Activation and inhibition of coagulation and fibrinolysis was analyzed in
bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged
chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and
interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation
and fibrinolysis was investigated in experiments in which the infusion of
endotoxin was combined with the administration of monoclonal anti-TNF-alpha or
anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in
bronchoalveolar thrombin generation as measured by levels of prothrombin
activation fragment F1+2 and thrombin-antithrombin complexes. Markers for
intrinsic pathway activation were not detectable, suggesting that the thrombin
generation was mediated by the tissue factor-dependent route. Levels of
antithrombin were low before the injection of endotoxin and not detectable
hereafter. The administration of anti-IL-6 antibody completely abolished the
endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment
with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar
fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was
significantly depressed after endotoxin injection, mainly due to a striking
increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin
induced effects on bronchoalveolar fibrinolysis could be blocked by the
simultaneous administration of anti- TNF-alpha antibodies. We conclude that
endotoxemia results in the activation of bronchoalveolar coagulation, which is
apparently mediated by the tissue factor route of coagulation activation and
which may be amplified by consumption of antithrombin III. Bronchoalveolar
fibrinolytic activity is significantly abolished by increased levels of mainly
PAI-2 after the injection of endotoxin. The endotoxin-induced effects on
bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha
seems to be the pivotal mediator of the endotoxin-induced depression of
bronchoalveolar fibrinolysis.
PMID- 9655713
TI - Allergen-induced early and late asthmatic responses are not affected by
inhibition of endogenous nitric oxide.
AB - Endogenous exhaled nitric oxide (NO) is increased during the late response to
inhaled allergen in patients with asthma and may be bronchoprotective in asthma
or have a deleterious effect when generated in excess under inflammatory
conditions. To investigate this, we evaluated the effect of inhibiting endogenous
NO production with nebulized NG-nitro-L-arginine methyl ester (L-NAME), a
nonselective NO synthase (NOS) inhibitor, on early and late asthmatic responses
to inhaled allergen in patients with mild allergic asthma. After a screening
allergen challenge (AC), 22 male patients attended two visits conducted in a
double-blind, randomized, placebo-controlled, crossover manner. Twelve patients
demonstrating an early asthmatic response only (single responders) inhaled either
L-NAME 170 mg or 0.9% saline 20 min before AC, with exhaled NO and FEV1 measured
for 3 h. Ten patients demonstrating both early and late asthmatic responses (dual
responders) were studied in a similar fashion but inhaled two further doses of L
NAME or placebo 3.5 and 7 h after the initial dose, with exhaled NO and FEV1
measured for 10 h. L-NAME reduced exhaled NO levels by 77 +/- 5% (p < 0.01) and
71 +/- 7% (p < 0.01) in single and dual responders, respectively, but had no
significant effect on early or late asthmatic responses. Following AC in single
responders, the mean (+/- SEM) maximum fall in FEV1 after L-NAME and saline was
21.2 +/- 2.9% and 23.8 +/- 3.0%, respectively, and in dual responders, 31.2 +/-
4.5% and 31.8 +/- 5. 8% during the early asthmatic responses, and 27.4 +/- 3.9%
and 30.6 +/- 4.5% during the late asthmatic responses, respectively. Area under
the curve (AUC) did not significantly differ. AUC0-2 h in single responders after
L-NAME and saline was 20.2 +/- 3.9 and 24.9 +/- 4.4 Delta% FEV1/h, and in dual
responders, 37.6 +/- 8.4 and 36.7 +/- 8.4 Delta% FEV1/h, respectively, and 106.2
+/- 18.9 and 117.1 +/- 22.4 Delta% FEV1/h, respectively, for the AUC4-10 h. This
study suggests that in mild allergic asthma, endogenous NO neither protects
against nor contributes to the processes underlying airway responses to inhaled
allergen.
PMID- 9655714
TI - Effects of spontaneous and hypercapnic hyperventilation on inspiratory effort
sensation in normal subjects.
AB - In order to elucidate if the inspiratory effort sensation (IES) associated with
carbon dioxide (CO2) is independent of the concomitant increase in the
ventilation, we studied 23 normal resting volunteers (mean age 34 +/- 11 yr)
during CO2 rebreathing. Our main goal was to compare the IES at the same
ventilation level under hypercapnic and isocapnic conditions. The protocol
included: (1) basal measurements (BASAL); (2) hypercapnic ventilation (HV); (3)
screen copy of ventilatory pattern during hypercapnia (COPY); (4) screen copy at
basal end-tidal (partial) carbon dioxide pressure (PETCO2) (ISO); and (5)
recovery (REC). During HV, PETCO2 increased to 54.8 +/- 0.78 mm Hg (p < 0.001)
and ventilation (VE) from 12.0 +/- 0.50 to 28.1 +/- 1.19 L/min (p < 0.001). Borg
value increased from 0.11 +/- 0.06 to 3.4 +/- 0.23 (p < 0.001). These values were
not different during HV and COPY. During ISO, PETCO2 was 40.2 +/- 0. 59 mm Hg
(not significant [NS] from BASAL), while VE remained unchanged: 29.9 +/- 1.29
L/min (NS from HV and COPY). Interestingly, the Borg value during the ISO
decreased to 1.86 +/- 0.28 (p < 0.001 compared with HV and COPY). The increased
IES induced by hypercapnic ventilation was reduced at the same ventilation level
during isocapnic conditions. We suggest that CO2 generates an IES independent of
the concomitant increase in ventilation.
PMID- 9655715
TI - Analysis of HLA-DPB1 polymorphisms in African-Americans with sarcoidosis.
AB - Several studies have found weak associations between certain human leukocyte
antigen (HLA) alleles and sarcoidosis, but none have been conclusive. Glutamic
acid at position 69 in HLA-DPB1 has been reported to be strongly associated with
chronic beryllium disease. The immunopathologic and clinical similarities between
chronic beryllium disease (CBD) and sarcoidosis suggest that similar immune
response genes may be involved in susceptibility in both diseases. We analyzed
the DNA sequence of HLA-DPB1 exon 2, which contains the hypervariable regions
involved in binding antigens, in blood samples from African-American sarcoidosis
patients and healthy controls. Results indicate that Val36 (odds ratio [OR] =
2.30) and Asp55 (OR = 2.03) are associated with increased risk for sarcoidosis,
but no association with Glu69 was found. These results suggest that although HLA
DPB1 Glu69 is not associated with sarcoidosis, other alleles may make some
contribution to susceptibility to sarcoidosis in African-Americans.
PMID- 9655716
TI - A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy.
AB - To evaluate the effect of a room high-efficiency particulate air (HEPA) cleaner
on cat-induced asthma and rhinitis, 35 cat-allergic subjects who were living with
one or more cats were studied in a double-blind, placebo controlled trial. After
a 1 mo baseline period, subjects' bedrooms were equipped with an active or
placebo air cleaner for the following 3 mo. Evaluations included monthly
measurement of cat-allergen levels, daily morning, afternoon, and nighttime nasal
and chest-symptom scores, twice-daily measurement of peak-flow rates, daily
medication scores, monthly spirometry, and methacholine (MCh) challenge testing
before and after the study. Airborne allergen levels were reduced in the active
filter group as compared with the placebo group (p = 0.045). However, no
differences were detected in settled-dust allergen levels (p = 0.485), morning,
afternoon, or nighttime nasal-symptom scores (p = 0.769, 0.534, and 0.138), chest
symptom scores (p = 0.388, 0.179, and 0.215), sleep disturbance (p = 0.101),
morning or afternoon peak-flow rates (p = 0. 424 and 0.679), or rescue medication
use (nasal, p = 0.164, chest, p = 0.650), respectively. Although the combination
of a HEPA room air cleaner, mattress and pillow covers, and cat exclusion from
the bedroom did reduce airborne cat-allergen levels, no effect on disease
activity was detected for any parameter studied.
PMID- 9655717
TI - Starting with a higher dose of inhaled corticosteroids in primary care asthma
treatment.
AB - New British guidelines on the treatment of asthma (9) advocate starting with a
higher dose of inhaled corticosteroids in newly detected asthma patients. We
investigated whether initiating inhaled steroid treatment with a higher dose is
clinically more effective than a lower dose in steroid naive patients with
asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo
treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice
a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200
microg budesonide once daily for all patients. Forty patients started with 400
microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean
age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline,
and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of
treatment with 400 microg and 100 microg budesonide twice daily mean morning peak
expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53),
respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1
to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests
that starting inhaled corticosteroids at a higher dose is not superior to a lower
dose in the treatment of newly detected asthma.
PMID- 9655718
TI - Inhaled corticosteroids and the prevention of readmission to hospital for asthma.
AB - Despite the proven efficacy of inhaled corticosteroids in reducing airway
inflammation and their increasing use for the treatment of asthma since the mid
1980s, hospitalization for asthma has been increasing in frequency in several
countries. Only few studies, reporting contradictory results, have investigated
the role of inhaled corticosteroids in the prevention of hospitalizations for
asthma. Using a cohort of 2,059 hospitalized asthmatic patients between 5 and 54
yr of age, we estimated the effectiveness of inhaled corticosteroids in
preventing a readmission to hospital for asthma as a function of the duration of
therapy. The cohort was selected from the databases of Saskatchewan Health from
1977 to 1993. The rate ratio (RR) of a readmission for asthma varied with
duration of regular therapy with inhaled corticosteroids. During the first 15 d
of regular therapy, users of inhaled corticosteroids were as likely as nonusers
of these medications to be readmitted for asthma with a RR of 1.2 (95% CI: 0.8
1.8). Subjects treated regularly with inhaled corticosteroids for at least 16 d
and as long as 6 mo were 40% less likely to be readmitted for asthma (RR = 0.6;
95% CI: 0.4-0.9), while after 6 mo of regular treatment the protective effect
disappeared (RR = 1.3; 95% CI: 0.7-2.4). We conclude that regular therapy with
inhaled corticosteroids can substantially reduce the risk of a readmission for
asthma after only 15 d of use. Confounding by severity appears as the most likely
explanation for the disappearance of the beneficial effect after 6 mo of regular
therapy.
PMID- 9655719
TI - Capitation, managed care, and chronic obstructive pulmonary disease.
AB - Expenditure and utilization patterns of aged Medicare beneficiaries with chronic
obstructive respiratory disease (COPD) (n = 42,472) were compared with all
Medicare beneficiaries (n = 1,221,615) using a 5% nationally representative
sample of aged Medicare beneficiaries participating in the fee-for-service
program in 1992. Per capita expenditures for an aged Medicare beneficiary with
COPD were 2.4 times the per capita expenditures for all Medicare beneficiaries.
The most expensive 10% of Medicare beneficiaries with COPD accounted for nearly
half of total expenditures for this population. Higher comorbidity, as measured
by the Deyo-adapted Charlson index, was associated with higher expenditures. For
Medicare Part B claims, internal medicine accounted for the largest portion of
physician expenditures (14%). Per capita expenditures for pulmonologists were 7.5
times higher for beneficiaries with COPD compared with all Medicare
beneficiaries. Results from this study suggest that there is a subgroup of
individuals with COPD who are likely to be very expensive during the year.
Additional analytic studies are needed to more specifically identify
characteristics associated with these individuals. As more Medicare beneficiaries
enroll in managed care and as physicians are increasingly being paid on a
capitated basis this information will be useful to physicians as they monitor the
care provided to patients and assess the financial risks they accept under
capitation.
PMID- 9655720
TI - Influence of pulmonary bacteriology and histology on the yield of diagnostic
procedures in ventilator-acquired pneumonia.
AB - We investigated the influence of pulmonary bacteriology and histology on the
yield of diagnostic procedures in a clinically relevant model of ventilator
acquired pneumonia (VAP). Twenty-seven piglets entered a 4-d protocol of
ventilatory support under general anesthesia. Endotracheal aspirates (EA),
protected specimen brush (PSB), and bronchoalveolar lavage (BAL) were obtained on
Day 4. PSB and BAL were performed under bronchoscopic guidance in dependent and
nondependent lung segments. Immediately thereafter sternotomy allowed bilateral
lung biopsies including the segments studied by bronchoscopic techniques. All
respiratory specimens were then processed for microscopic examination and
quantitative cultures (QC). In this model where many of the confounding factors
often present in human studies were absent, we found that (1) although the local
bacterial burden tended to correlate with the presence and the severity of
histologic lesions, no definite bacteriologic cutoff could differentiate the
histologic presence or absence of pneumonia; (2) histologic lesions of pneumonia
and parenchymal bacterial burden were unevenly distributed through the lungs; (3)
this heterogeneity in bacterial distribution also held true for single bacterial
species; (4) using discriminative values of >= 10(3) cfu/ml, >= 10(4) cfu/ml, and
>= 10(5) cfu/ml to define positive PSB, BAL, and EA cultures, respectively, these
techniques identified the histologic presence of pneumonia with a sensitivity of
69%, 78%, and 100%, respectively; (5) the specificity of these techniques in
recognizing VAP was less than 50%; (6) with these discriminative values, less
than 50% of PSB and BAL specimens correctly identified the causative organisms,
whereas 94% of EA specimens correctly established the microbiologic diagnosis of
pneumonia. We believe that the peculiar histologic and bacteriologic features of
VAP may account for the difficulties of PSB and BAL, which combine QC with the
use of discriminative thresholds, to reliably recognize pneumonia and to identify
the causative organisms. For clinical practice, no technique confidently helps in
recognizing pneumonia in mechanically ventilated patients. With regard to
bacterial diagnosis, use of quantitative cultures of EA seems to be the best
technique to identify the causative organisms in patients suffering VAP.
PMID- 9655721
TI - Effect of continuous positive airway pressure on forced expiratory flows in
infants with tracheomalacia.
AB - Continuous positive airway pressure (CPAP) is used to minimize airway collapse in
infants with tracheomalacia. Forced expiratory flows (FEFs) at functional
residual capacity (FRC) increase with increasing CPAP in infants with
tracheomalacia, and it has been suggested that CPAP prevents airway collapse by
"stenting" the airway open. Since FEF is greater at higher than at lower lung
volumes, we evaluated whether the increase in flow measured at FRC (V FRC) with
CPAP could be explained by the increase in FRC with CPAP. We measured full FEF
volume curves at CPAP levels of 0, 4, and 8 cm H2O in six infants with
tracheomalacia and five healthy control infants. In both groups of infants, FVC
did not change with CPAP; however, inspiratory capacity (IC) decreased and thus
FRC increased with increasing CPAP. FEFs at FRC increased with increasing levels
of CPAP; however, the FEFs at 50% and 75% of expired volume were not different
for the three levels of CPAP for both groups of infants. Our finding that FEFs
measured at the same lung volumes did not differ for the different levels of CPAP
indicates that CPAP affects forced flows primarily by increasing lung volume.
PMID- 9655722
TI - Airway mucosal blood flow in bronchial asthma.
AB - As an inflammatory airway disease, asthma is expected to be associated with an
increase in airway blood flow. We therefore compared airway mucosal blood flow
(Qaw) among normal subjects (n = 11) and patients with stable asthma receiving (n
= 13) or not receiving (n = 10) long-term inhaled glucocorticosteroid (GS)
therapy. Qaw was calculated from the uptake of dimethyl ether in the anatomic
dead space minus the most proximal 50 ml (DS), and expressed as blood flow per ml
DS. Mean (+/- SE) Qaw was 38.5 +/- 5. 3 microl . min-1 . ml-1 in normals, 68.2 +/
7.9 microl . min-1 . ml-1 in GS-naive asthmatics (p < 0.01), and 55.4 +/- 5.3
microl . min-1 . ml-1 in GS-treated asthmatics (p < 0.05). Ten minutes after
administration of 180 microg albuterol by metered dose inhaler, mean Qaw
increased by 83 +/- 26% in normal subjects (p < 0.01), but did not change
significantly in GS-naive (+5 +/- 8%) or GS-treated (+32 +/- 15%) asthmatics.
These results demonstrate that Qaw is increased in stable asthmatics and
resistant to further increase by a standard inhaled dose of a beta-adrenergic
agonist.
PMID- 9655723
TI - Paradoxical worsening of tuberculosis following antiretroviral therapy in
patients with AIDS.
AB - Transient worsening of tuberculous symptomatology and lesions following
antituberculous therapy (paradoxical response) has previously been described as a
rare occurrence. To determine the incidence of paradoxical responses in patients
with AIDS and TB who are treated with antituberculous therapy and subsequently
with combination antiretroviral therapy (ARV), we conducted a prospective study
of 33 HIV-seropositive TB patients treated with anti-TB therapy and
antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients
treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients
treated with anti-TB therapy but not on antiretrovirals (historical control;
Group 3). In Group 1 patients, paradoxical responses were temporally more related
to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD:
15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently
(12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3
(2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical
responses and received tuberculin purified protein derivative (PPD) in Group 1
had their tuberculin skin tests convert from negative to strongly positive after
ARV. These observations suggest that a paradoxical response associated with
enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV
infected TB patients. Furthermore, the skin test conversion after the initiation
of ARV may have important public health implications.
PMID- 9655724
TI - Differences in familial segregation of FEV1 between asthmatic and nonasthmatic
families. Role of a maternal component.
AB - Studies have demonstrated familial aggregation of lung function. This study
employed segregation analysis to investigate the mode of inheritance of FEV1
using regressive models for continuous traits. The study population comprised 309
families (1,163 individuals) enrolled in the Tucson Children's Respiratory Study
who had both parents and at least one child with FEV1 data. Results showed
significant genetic heterogeneity among the 87 families (328 individuals) with at
least one member with asthma and the 222 families (835 individuals) with no
asthmatic members. In families with no asthmatic members, all statistical models
were rejected, indicating the absence of a major gene controlling lung function.
However, a significant familial component indicated a strong
polygenic/multifactorial mode of inheritance. In families with asthmatic
member(s), results suggested polygenic/multifactorial inheritance with weak
evidence for a Mendelian component expressed in a recessive fashion. However,
while both father-offspring and mother-offspring correlations were statistically
significant in families with no asthmatic members, only the mother-offspring
correlation was significant in families with asthmatic members. The data suggest
that lung function is inherited as a polygenic/multifactorial trait, but in
asthmatic families a major element of intergenerational correlation is associated
with a maternal influence, which may be genetically or environmentally mediated.
PMID- 9655725
TI - Environmental tobacco smoke and adult asthma. The impact of changing exposure
status on health outcomes.
AB - The effect of environmental tobacco smoke (ETS) exposure on adults with asthma
has not been well characterized. In a prospective cohort study of 451 nonsmoking
adults with asthma, we evaluated the impact of ETS exposure on asthma severity,
health status, and health care utilization over 18 mo. There were 129 subjects
(29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three
categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline
exposure and new exposure at follow-up (n = 56, 12%), and exposure at both
baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with
baseline ETS exposure had greater severity-of-asthma scores (score difference,
1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score
difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes
Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0)
than unexposed subjects. They also had greater odds of emergency department
visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR =
1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In
longitudinal follow-up, subjects reporting ETS cessation showed improvement in
severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and
physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1).
Environmental tobacco smoke cessation decreased the odds of emergency department
visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04
0.97) after adjustment for covariates. Environmental tobacco smoke initiation was
associated with greater asthma severity only in subjects with high-level (>= 3
h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self
reported ETS exposure is associated with greater asthma severity, worse health
status, and increased health care utilization in adults with asthma.
PMID- 9655726
TI - Parental history and the risk for childhood asthma. Does mother confer more risk
than father?
AB - Although heredity plays a major role in asthma and in other allergic diseases,
mechanisms underlying the inheritance of these disorders are poorly understood,
as is the relative contribution of maternal and paternal conditions to risk of
disease. We investigated doctor-diagnosed maternal and paternal asthma, eczema,
and hay fever as cross-sectional predictors of childhood asthma and allergic
disease in 306 children with a median age of 3.5 yr from families in which at
least one parent had a history of either asthma or other allergic conditions. For
both childhood asthma and eczema, the strongest parental predictors were the same
conditions in the parents. For asthma in particular, maternal asthma was most
strongly associated with asthma in the child over all ages in both univariate (OR
= 3.2, 95% CI = 1.5 to 6.7) and multivariable (OR = 4.1, 95% CI = 1.7 to 10.1)
models. Paternal asthma was weakly associated with childhood asthma in the
univariate model (OR = 1.4, 95% CI = 0.6 to 3.2), but this association increased
in magnitude in the multivariable model (OR = 2.7, 95% CI = 1.0 to 7.2). Among
the children < 5 yr of age, the risk for childhood asthma associated with
maternal asthma (OR = 5.0, 95% CI = 1.7 to 14.9) was greater than the risk
associated with paternal asthma (OR = 1.6, 95% CI = 0. 5 to 5.9), whereas both
maternal asthma and paternal asthma were associated with similar risks among
children >= 5 yr of age (OR = 4. 6, 95% CI = 1.1 to 19.0 and OR = 4.1, 95% CI =
1.0 to 16.0, respectively). The odds of having a child with asthma were three
times greater in families with one asthmatic parent and six times greater in
families with two asthmatic parents than in families where only one parent had
inhalant allergy without asthma; furthermore, inhalant allergy in one parent also
conferred additional risk in the presence of asthma in the other parent. Further
investigation is needed into the relative importance of genetic factors and in
utero and postnatal exposures in determining the differential effects of maternal
and paternal asthma on the development of childhood asthma.
PMID- 9655727
TI - Molecular markers of acute upper airway inflammation in workers exposed to fuel
oil ash.
AB - Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence
and severity of upper airway inflammation. We studied 18 boilermakers overhauling
a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk.
NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We
measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic
cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel
oil ash exposure. In boilermakers, MPO was elevated during boiler work versus
preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk
postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8
levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8
pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p <
0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median
< 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7
versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change
significantly during the study. Utility workers showed no significant change in
any marker during the study period. Particulate matter < 10 micro(m) (PM10)
levels were higher for boilermakers than for utility workers before boiler work
(geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was
more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001).
Ozone levels were low during the study. These data suggest that exposure to fuel
oil ash results in acute upper airway inflammation, potentially mediated by
increased IL-8 levels and the recruitment and activation of polymorphonuclear
leukocytes. These changes were associated with significantly increased PM10
levels and concentrations of upper airway vanadium.
PMID- 9655728
TI - Prognostic value of hypercapnia in patients with chronic respiratory failure
during long-term oxygen therapy.
AB - Hypercapnia observed in patients with chronic respiratory failure may not be an
ominous sign for prognosis when they are receiving long-term oxygen therapy
(LTOT). In this study, we selected 4,552 patients with chronic obstructive
pulmonary disease (COPD) and 3,028 with sequelae of pulmonary tuberculosis (TBsq)
receiving LTOT from 1985 to 1993 throughout Japan and prospectively analyzed
their prognoses. The hypercapnic patients (PaCO2 >= 45 mm Hg) had a better
prognosis than the normocapnic patients (35 <= PaCO2 < 45 mm Hg) for TBsq, but no
difference was found between the two groups with COPD. Furthermore, Cox's
proportional hazards model revealed that in TBsq hypercapnia was an independent
factor for favorable prognosis, and that the relative risk for mortality was 0.76
in patients with 45 <= PaCO2 < 55 mm Hg, 0.64 for those with 55 <= PaCO2 < 65 mm
Hg, and 0. 49 for patients with PaCO2 >= 65 mm Hg against normocapnic patients.
This favorable effect of hypercapnia in TBsq was particularly apparent in the
patients without severe airway obstruction. Even a rise of 5 mm Hg or more in
PaCO2 over the initial 6- to 18-mo follow-up period was not associated with poor
prognosis in TBsq, although it was in COPD. From these findings, we conclude that
hypercapnia should not be generally considered an ominous sign for prognosis in
those patients who receive LTOT.
PMID- 9655729
TI - The pressure-volume curve is greatly modified by recruitment. A mathematical
model of ARDS lungs.
AB - A mathematical model of the ARDS lung, with simulated gravitational superimposed
pressure, evaluated the effect of varying alveolar threshold opening pressures
(TOP), PEEP and peak inspiratory pressure (PIP) on the static pressure-volume
(PV) curve. The lower inflection point (Pflex) was affected by SP and TOP, and
did not accurately indicate PEEP required to prevent end-expiratory collapse.
Reinflation of collapsed lung units (recruitment) continued on the linear portion
of the PV curve, which had a slope at any volume greater than the total
compliance of aerated alveoli. As recruitment diminished, the reduced PV slope
could produce an upper Pflex at 20 to 30 cm H2O pressure. An upper Pflex caused
by alveolar overdistension could be modified or eliminated by recruitment with
high TOP. With constant PIP as PEEP increased, and TOP range of 5 to 60 cm H2O,
PEEP to prevent end-expiratory collapse was indicated by minimum PV slope above
20 cm H2O, minimum hysteresis, and maximum volume at a pressure of 20 cm H2O.
With constant inflation volume as PEEP increased, the effect on PV slope was
unpredictable. Although increased PV slope indicated recruitment, maximum PV
slope usually underestimated PEEP required to prevent end-expiratory collapse.
Therefore, with this model the PV curve did not reliably predict optimal
ventilator settings.
PMID- 9655730
TI - Airway hyperresponsiveness in asthma. Not just a problem of smooth muscle
relaxation with inspiration.
AB - Airway hyperresponsiveness in asthma has been attributed to impaired ability of
deep inspiration (DI) to stretch airway smooth muscle. We have retested this
hypothesis by comparing the responses to methacholine of 10 asthmatic and 10
control subjects. After each dose subjects breathed tidally without deep
inspiration for 4 min, followed by a forced partial expiration from which flow
was measured at a constant volume, 35% baseline VC (Vp 35). This index is
independent of both DI and increases in end-inspiratory lung volume (EILV). EILV
increased significantly more in the asthmatic group than in the control group
(15.0 versus 2.5% of baseline VC, p = 0. 019), a factor that if not taken into
account would tend to mask the difference in the two responses. Comparisons were
made after a cumulative dose of 50 microg methacholine, which was the highest
dose common to all subjects. The asthmatic response was significantly greater
than that seen in the control group, with reductions to 25.9 and 72.1% of
baseline Vp 35, respectively (p = 0. 0007). We conclude that the sensitivity of
asthmatic airways to methacholine is greater than that of normal airways even
when DI is prohibited. Therefore, the hyperresponsiveness of asthmatic airways is
not attributable simply to an inability of DI to stretch airway smooth muscle.
PMID- 9655731
TI - Total sputum nitrate plus nitrite is raised during acute pulmonary infection in
cystic fibrosis.
AB - Nitric oxide (NO) can be detected in exhaled gas in human subjects. It is
produced by nitric oxide synthase (NOS) and is rapidly metabolized to nitrite and
nitrate (NO2/NO3). Exhaled NO is reported to be elevated in patients with asthma,
bronchiectasis, or upper respiratory tract infection. Recent reports have shown
no increase of exhaled NO in stable cystic fibrosis (CF). We hypothesized that
NOS activity is increased in patients with acute pulmonary exacerbation of CF. We
therefore measured exhaled NO and sputum NO2/NO3 in three subject categories:
patients with acute pulmonary exacerbation of CF, patients with stable CF, and
healthy control subjects. Mean +/- SD exhaled NO was significantly higher in
control subjects (8.8 +/- 4.9 ppb) than in both acute (3.8 +/- 3.9 ppb) and
stable (5.0 +/- 2.5 ppb) patients. Sputum NO2/NO3 was significantly higher in
acute patients (774 +/- 307 micromol/L) when compared with both stable patients
(387 +/- 203 micromol/L) and control (421 +/- 261 micromol/L) subjects. Sputum
NO2/NO3 did not return to normal in a subgroup of patients assessed after 2 wk of
intensive antibiotic and glucocorticoid treatment. These results confirm that
exhaled NO is not a useful measure of airway inflammation in CF. Elevated levels
of sputum NO2/NO3 suggest that NOS is activated during acute pulmonary
exacerbations of CF.
PMID- 9655732
TI - Addition of salmeterol versus doubling the dose of beclomethasone in children
with asthma. The Dutch Asthma Study Group.
AB - Studies in adults revealed that addition of salmeterol to a moderate dose of
inhaled corticosteroid resulted in better symptom control and higher PEF compared
with doubling the dose of inhaled corticosteroid. The aim of this three group
study was to compare the effects of a moderate dose of beclomethasone, the same
dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on
lung function and symptoms in children with moderate asthma. A total of 177
children already treated with inhaled corticosteroids, were randomized in a
double-blind parallel study either to salmeterol 50 microg twice daily
(BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo
(BDP400) in addition to beclomethasone 200 microg twice daily. No significant
differences between groups were found in FEV1, PD20 methacholine, symptom scores,
and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in
the first months of treatment. FEV1, and PD20 methacholine significantly improved
in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95%
CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm,
BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95%
CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling
doses. Growth was significantly slower in the BDP800 group. We conclude that no
additional benefit was found of adding either salmeterol or more beclomethasone
to a daily dose of 400 microg beclomethasone in this group of children with
excellent compliance of medication.
PMID- 9655733
TI - Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A
randomized prospective study. Members of the Lung Study Group.
AB - Twenty-six symptomatic subjects with clinical evidence plus either high
resolution computed tomography (HRCT, n = 25) or open-lung biopsy (OLB, n = 1)
patterns typical for idiopathic usual interstitial pneumonia (idiopathic UIP)
were entered into a randomized prospective treatment trial using high-dose
prednisone (n = 12) versus colchicine (n = 14). The minimum dose of prednisone
used was 60 mg/d for 1 mo, tapered to 40 mg/d over the second month, tapered to
40 mg every other day during the third month, with subsequent doses adjusted as
clinically indicated. The dose of colchicine was 0.6-1.2 mg/d, as tolerated. The
presence of a rim of subpleural honeycomb change was present in all of the 25
subjects who had HRCT. Subjects treated with high-dose prednisone alone
experienced a higher incidence of serious side effects and also exhibited a trend
(not statistically significant, p = 0.391) to more rapid decline of pulmonary
function and shortened survival than did those treated with colchicine alone. In
most subjects with typical clinical and HRCT features of idiopathic UIP, neither
prednisone nor colchicine resulted in objective improvement, and the disease
continued to progress in the majority. Colchicine appears to be a safer
alternative to a trial of high-dose prednisone but may be no different than no
therapy.
PMID- 9655734
TI - Antioxidant supplementation and respiratory functions among workers exposed to
high levels of ozone.
AB - Ozone exposure has been related to adverse respiratory effects, in particular to
lung function decrements. Antioxidant vitamins are free-radical scavengers and
could have a protective effect against photo-oxidant exposure. To evaluate
whether acute effects of ozone on lung functions could be attenuated by
antioxidant vitamin supplementation, we conducted a randomized trial using a
double-blind crossover design. Street workers (n = 47) of Mexico City were
randomly assigned to take daily a supplement (75 mg vitamin E, 650 mg vitamin C,
15 mg beta carotene) or a placebo and were followed from March to August 1996.
Pulmonary function tests were done twice a week at the end of the workday. During
the follow-up, the mean 1-h maximum ozone level was 123 ppb (SD = 40). During the
first phase, ozone levels were inversely associated with FVC (beta = -1.60
ml/ppb), FEV1 (beta = -2.11 ml/ppb), and FEF25-75 (beta = -4.92 ml/ppb) (p <
0.05) in the placebo group but not in the supplement group. The difference
between the two groups was significant for FVC, FEV1, and FEF25-75 (p < 0.01).
During the second phase, similar results were observed, but the lung function
decrements in the placebo group were smaller, suggesting that the supplementation
may have had a residual protective effect on the lung. These results need to be
confirmed in larger supplementation studies.
PMID- 9655735
TI - Increased expression of high affinity IgE (FcepsilonRI) receptor-alpha chain mRNA
and protein-bearing eosinophils in human allergen-induced atopic asthma.
AB - FcepsilonRI receptors play an important role in allergen-induced mediator release
and antigen presentation by mast cells, basophils, and monocyte/macrophages in
atopic disorders. The expression of FcepsilonRI by tissue eosinophils in atopic
asthma after allergen challenge has not been established. For this reason we
attempted to identify mRNA and protein product + FcepsilonRIalpha eosinophils in
cytospins made from bronchoalveolar lavage (BAL) from atopic asthmatics (n = 9)
and nonatopic normal subjects (n = 4) 24 h after segmental challenge with
allergen or diluent. Messenger RNA for FcepsilonRIalpha was determined using in
situ hybridization and FcepsilonRIalpha protein expression by immunocytochemistry
using a mouse monoclonal antibody 22E7. Colocalization of FcepsilonRIalpha
receptors to eosinophils was performed using chromotrope 2R. When compared with a
control challenge, segmental challenge with Dermatophagoides pteronyssinus
induced significant BAL eosinophilia (p = 0.007). The total number of BAL
FcepsilonRIalpha mRNA and protein-positive cells also increased in asthmatics,
median values 2 (0.7-7.2) and 11.5 (0.6-65.0) x 10(6) cells (p = 0.02) and 0 (0
0.3 x 10(6)) and 3.1 x 10(6) (0.45 - 162.5 x 10(6)) cells (p = 0.007),
respectively, for mRNA and protein. Net increases in FcepsilonRIalpha+ cells
correlated with the net increases in BAL eosinophils (r = 0.98, p = 0.0001 for
mRNA and r = 0.72, p = 0.02 for protein). Colocalization studies with chromotrope
2R revealed that only 4% of FcepsilonRIalpha+ cells were eosinophils after
control challenge and, in contrast, 85 to 95% of FcepsilonRIalpha+ cells were
eosinophils after allergen. There were no differences in the numbers of
FcepsilonRIalpha+ cells or eosinophils in normal control subjects. Our results
demonstrated that local endobronchial allergen provocation in atopic asthmatics
results in increased synthesis and expression of FcepsilonRIalpha predominantly
on BAL eosinophils.
PMID- 9655736
TI - Effects of rhinovirus infection on hydrogen peroxide- induced alterations of
barrier function in the cultured human tracheal epithelium.
AB - To investigate whether rhinovirus infection impairs epithelial barrier functions,
human rhinovirus 14 (HRV-14) was infected to primary cultures of human tracheal
epithelial cells and experiments were performed on Day 2 after HRV-14 infection.
Hydrogen peroxide (H2O2; 3 x 10(-)4 M) increased electrical conductance (G)
across the epithelial cell sheet measured with Ussing's chamber methods. Exposure
of the epithelial cells to HRV-14 had no effect on H2O2-induced increases in G
and [3H]mannitol flux through the cultured epithelium in the control condition,
but it markedly potentiated H2O2- induced increases in both parameters in IL
1beta (100 U/ml) pretreated condition. However, pretreatment with TNF-alpha (100
U/ml) was without effect. IL-1beta enhanced the intercellular adhesion molecule-1
(ICAM-1) expression assessed by immunohistochemical analysis and susceptibility
of epithelial cells to HRV-14 infection. An antibody to ICAM-1 inhibited HRV-14
infection of epithelial cells and abolished H2O2-induced increases in G and
[3H]mannitol flux in IL-1beta-pretreated epithelial cells with HRV-14 infection.
These results suggest that rhinovirus infection may reduce barrier functions in
the airway epithelium in association with upregulation of ICAM-1 expression.
PMID- 9655737
TI - Computer tomographic assessment of perfluorocarbon and gas distribution during
partial liquid ventilation for acute respiratory failure.
AB - The average in vivo chest computed tomographic (CT) attenuation number (air =
1,000, soft tissue = 0, perflubron = +2,300 Hounsfield units [HU]) of 10
ventrodorsal-oriented lung segments was calculated to assess the distribution of
gas and perflubron in 14 oleic acid lung-injured adult sheep during partial
liquid ventilation (PLV, n = 7) or gas ventilation (GV, n = 7). Partial liquid
ventilation was associated with a significant decrease in shunt fraction (PLV =
40 +/- 12%, GV = 76 +/- 12%, p = 0.004). Computed tomographic attenuation data
during expiration (HUexp) demonstrated minimal gas aeration in GV animals in the
dependent (segments 6-10) lung zones (HUexp = -562 +/- 108 for segments 1-5,
HUexp = -165 +/- 104 for segments 6-10, p = 0.015). During PLV, perflubron was
predominantly distributed to the dependent lung regions (HUexp = 579 +/- 338 for
segments 1-5, HUexp = 790 +/- 149 for segments 6-10, p = 0.04). The ratio of the
inspiratory to expiratory HU (HUinsp/exp) was greater in dependent than
nondependent regions (mean HUinsp/exp segments 1-5 = 0.56, segments 6-10 = 0.81,
p = 0.01), indicating that during inspiration relatively more gas than perflubron
was distributed to the nondependent lung regions. We conclude that during PLV in
this lung injury model, (1) gas exchange is improved when compared with gas
ventilation, (2) perflubron is distributed predominantly to the dependent regions
of the lung, and (3) although gas is distributed throughout the lung with each
inspiration, more gas than perflubron goes to the nondependent lung regions.
PMID- 9655738
TI - Inhibitors of elastase in airway lavage samples from ventilated preterm human
neonates.
AB - Surplus elastase released from neutrophils during lung injury is balanced mainly
by alpha1-protease inhibitor (alpha1-PI) and by two acid-resistant inhibitors.
The latter include mucus protease inhibitor (MPI, also named SLPI, BSI, ALP) and
elastase-specific inhibitor (ESI or Elafin), but their functional role during the
neonatal period has not yet been characterized precisely. The saline airway
lavage samples from neonates intubated for respiratory distress were separated by
centrifugation into a cellular and a soluble, supernatant fraction and then
analyzed. During the first 36 h of life (42 neonates, gestational age 24-40 wk),
elastase activity was confined to the cellular fraction. Thirty percent of the
acid-resistant inhibitors but almost no alpha1-PI, was cell-associated. In the
soluble fraction, about 20-30% of the acid-resistant inhibitors was functionally
active, but only about 10% of alpha1-PI was. In seven infants with a nosocomial
infection and deterioration during mechanical ventilation, only a very modest
increase in elastase activity was observed. However, the functional activity of
the acid-resistant inhibitors was reduced in the soluble fraction, whereas total
mass remained unchanged. A full assessment of protease and protease inhibitors
should include the cellular and the soluble lavage compartments.
PMID- 9655739
TI - Immunization and challenge with toluene diisocyanate decrease tachykinin and
calcitonin gene-related peptide immunoreactivity in guinea pig central airways.
AB - Toluene diisocyanate (TDI) is a potent sensitizer that causes occupational asthma
in a significant proportion of subjects exposed. We used an animal model to
investigate whether neuropeptide changes occur in the airways of immunized and
TDI-challenged guinea pigs. Animals were immunized by weekly intradermal
injections, challenged with TDI (5 to 20 ppb) after the third injection, and
killed 6 h after exposure. Control guinea pigs received injections of saline.
Lung tissue was processed immediately and analyzed for nerves using the
streptavidin-biotin complex peroxidase method with antisera to the neural marker
protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-
related peptide (CGRP). We also quantified the inflammatory infiltrate in the
submucosa of central airways, and we measured the serum level of specific IgG and
IgG1. Specific antibodies against TDI were present only in immunized animals.
Immunized as compared with nonimmunized animals had a significant increase in
eosinophils in the submucosa of central airways, and a further increase was
observed 6 h after TDI challenge. Immunization and TDI challenge did not modify
the number of mononuclear cells in the submucosa of central airways in both
nonimmunized and immunized animals. TDI exposure did not change the overall
innervation in both nonimmunized and immunized animals, but the density of PGP
9.5-positive nerves was significantly different between nonimmunized and
immunized TDI-challenged animals. The density of SP-, and CGRP-immunostained
nerves was significantly lower in immunized TDI-challenged than in nonimmunized
animals. TDI exposure significantly decreased the density of SP-positive nerves
in nonimmunized animals. A negative relationship was found between the presence
of airway inflammation, as indexed by eosinophil cell infiltration, and the
density of PGP 9.5-, SP-, and CGRP-immunostained nerves. In conclusion, TDI
produces airway inflammation and neuropeptides changes in the central airways of
immunized guinea pigs 6 h after TDI challenge. These findings support an
interaction between tachykinins, inflammatory (i.e., eosinophils) and possibly
immune cells.
PMID- 9655740
TI - Effects of rSP-C surfactant on oxygenation and histology in a rat-lung-lavage
model of acute lung injury.
AB - We have tested two surfactant preparations with the same phospholipid (PL)
composition, containing recombinant surfactant protein-C (rSP-C surfactant) and
without SP-C (plain PL surfactant). The effects of rSP-C surfactant were compared
with the bovine-derived surfactant preparations Alveofact, bLES, and Infasurf in
a lung lavage model, with surfactant given 1 h after the last lavage. The effects
of surfactant treatment on histopathologic changes (e.g., hyaline-membrane
formation) and improvement of oxygenation were compared with changes in untreated
controls. The surfactants were given in doses of 25, 50, and 100 mg PL/kg body
weight. At 120 min after treatment, only the protein-containing surfactants
showed a statistically significant increasing dose dependence with respect to
improving oxygenation. The values were 318 +/- 120 mm Hg, 443 +/- 58 mm Hg, and
480 +/- 43 mm Hg (mean +/- SD) for the three doses of rSP-C surfactant and 105 +/
81 mm Hg, 100 +/- 69 mm Hg, and 131 +/- 108 mm Hg for the three doses of PL
surfactant. The respective values for Alveofact were 104 +/- 81 mm Hg, 105 +/- 93
mm Hg, and 260 +/- 143 mm Hg; for bLES 373 +/- 138 mm Hg, 441 +/- 88 mm Hg, and
467 +/- 43 mm Hg; and for Infasurf 146 +/- 96 mm Hg, 284 +/- 178 mm Hg, and 436
+/- 70 mm Hg. The oxygen values of controls remained low, at 74 +/- 46 mm Hg.
Only the protein-containing surfactants dose-dependently inhibited the formation
of hyaline membranes. We conclude that rSP-C surfactant is at least as effective
as bovine-derived surfactants. Furthermore, the data imply that the difference
between plain PL surfactant preparations and bovine-derived surfactant
preparations containing both SP-B and SP-C can be overcome by addition of SP-C.
PMID- 9655741
TI - Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and
message.
AB - During transitional circulation, the pulmonary vascular bed undergoes a rapid and
profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'
Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of
pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is
achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP
specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have
investigated the levels of pulmonary PDE5 enzymatic activity, protein, and
messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We
report that within 1 h following birth, PDE5 activity, protein, and mRNA levels
decrease in both species, in a manner that correlates with known decreases in PVR
in early transition. However, from 4 to 7 d following birth, a secondary increase
in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung,
suggesting a complex regulation of PVR and VSM proliferation in late perinatal
development. Our data imply that PDE5 may be an important mediator in the
regulation of PVR in normal and possibly in pathologic states, and may ultimately
provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.
PMID- 9655742
TI - Long-term particulate and other air pollutants and lung function in nonsmokers.
AB - The associations between lung function measures (spirometry and peak expiratory
flow lability) and estimated 20-yr ambient concentrations of respirable
particles, suspended sulfates, sulfur dioxide, ozone, and indoor particles were
studied in a sample of 1,391 nonsmokers followed since 1977. Differences in air
pollutants across the population were associated with decrements of lung
function. An increase of 54 d/yr when particles < 10 micro(m) in diameter (PM10)
exceeded 100 microg/m3 was associated with a 7.2% decrement in FEV1, as percent
of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay
fever and with increased peak expiratory flow lability of 0.8% for all females
and 0.6% for all males. An increase in mean SO4 concentration of 1.6 microg/m3
was associated with a 1.5% decrement in FEV1, as percent of predicted, in all
males. An increase of 23 ppb of ozone as an 8-h average was associated with a
6.3% decrement in FEV1, as percent of predicted, in males whose parents had
asthma, bronchitis, emphysema, or hay fever.
PMID- 9655743
TI - Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and
hypoxia. Role in acute lung injury.
AB - LPS and selected cytokines upregulate xanthine dehydrogenase/xanthine oxidase
(XDH/XO) in cellular systems. However, the effect of these factors on in vivo
XDH/XO expression, and their contribution to lung injury, are poorly understood.
Rats were exposed to normoxia or hypoxia for 24 h after treatment with LPS (1
mg/kg) and IL-1beta (100 microg/kg) or sterile saline. Lungs were then harvested
for measurement of XDH/XO enzymatic activity and gene expression, and pulmonary
edema was assessed by measurement of the wet/dry lung weight ratio (W/D).
Although treatment with LPS + IL-1beta or hypoxia independently produced a 2-fold
elevation (p < 0. 05 versus exposure to normoxia and treatment with saline) in
lung XDH/XO activity and mRNA, the combination of LPS + IL-1beta and hypoxia
caused a 4- and 3.5-fold increase in these values, respectively. XDH/XO protein
expression was increased 2-fold by hypoxia alone and 1.3-fold by treatment with
LPS + IL-1beta alone or combination treatment. Compared with normoxic lungs, W/D
was significantly increased by exposure to hypoxia, LPS + IL-1beta, or
combination treatment. This increase was prevented by treatment of the animals
with tungsten, which abrogated lung XDH/XO activity. In conclusion, LPS, IL
1beta, and hypoxia significantly upregulate lung XDH/XO expression in vivo. The
present data support a role for this enzyme in the pathogenesis of acute lung
injury.
PMID- 9655744
TI - Partitioning of lung and chest-wall mechanics before and after lung-volume
reduction surgery.
AB - In the study reported here, we partitioned the mechanics of the respiratory
system into lung and chest-wall components, using the rapid occlusion technique
in seven patients with severe emphysema before lung-volume-reduction surgery and
3 mo later. Patients showed improvements in 6-min walk (p < 0.01) and dyspnea (p
< 0.05). The resistances of the respiratory system and chest wall were not
altered by surgery. Ohmic airway resistance did not change, but the component of
lung resistance (DeltaRL) due to viscoelastic behavior (stress relaxation) and
time-constant inhomogeneities (pendelluft) decreased in six patients (p < 0.03).
Dynamic elastance of the lung (Edyn,L) decreased after surgery (p < 0.02),
whereas dynamic elastance of the chest wall did not change. The ratio of dynamic
intrinsic positive end-expiratory pressure (PEEPi) to static PEEPi, which also
reflects viscoelastic properties and time-constant inhomogeneities, increased
after surgery (p < 0.05). The decrease in dyspnea was related to the decrease in
Edyn,L (r = 0.81, p = 0.03), and tended to be related to the decrease in DeltaRL
(r = 0.71, p = 0. 07). In conclusion, lung-volume-reduction surgery decreased
dynamic pressure dissipations caused by stress relaxation and time-constant
inhomogeneities within lung tissue, and it had no effect on the static mechanical
properties of the chest wall.
PMID- 9655745
TI - Increased carbon monoxide in exhaled air of subjects with upper respiratory tract
infections.
AB - Viral infection may induce the expression of heme oxygenase, resulting in
increased carbon monoxide (CO) formation. CO may be produced by various cells of
the upper and lower respiratory tract and may be detected in the exhaled air.
Therefore, exhaled CO concentrations were measured on a CO monitor by vital
capacity maneuver in subjects with upper respiratory tract infections (URTIs) and
in nonsmoking and smoking healthy control subjects. At the time of symptoms of
URTI, exhaled CO concentrations were 5.6 +/- 0.4 ppm and decreased to 1.0 +/- 0.1
ppm during recovery. Recovery values of exhaled CO were similar to those in age
matched nonsmoking healthy control subjects (1.2 +/- 0.3 ppm). Smoking healthy
control subjects had the highest levels of exhaled CO concentration among the
groups (18.5 +/- 2.5 ppm). These findings suggest that symptomatic URTIs increase
the concentration of CO in exhaled air. This may reflect the induction of heme
oxygenase that has an antiviral effect in the airways.
PMID- 9655746
TI - Exhaled nitric oxide (NO) is reduced shortly after bronchoconstriction to direct
and indirect stimuli in asthma.
AB - Exhaled NO is increased in patients with asthma and may reflect disease severity.
We examined whether the level of exhaled NO is related to the degree of airway
obstruction induced by direct and indirect stimuli in asthma. Therefore, we
measured exhaled NO levels before and during recovery from histamine and
hypertonic saline (HS) challenge (Protocol 1) or histamine, adenosine 5'
monophosphate (AMP), and isotonic saline (IS) challenge (Protocol 2) in 11 and in
nine patients with mild to moderate asthma, respectively. The challenges were
randomized with a 2-d interval. Exhaled NO and FEV1 were measured before and at
4, 10, 20, and 30 min after each challenge. NO was measured during a slow VC
maneuver with a constant expiratory flow of (0.05 x FVC)/s against a resistance
of 1 to 2 cm H2O. Baseline exhaled NO levels were not significantly different
between study days in Protocol 1 (mean +/- SD: 4.8 +/- 1.8 ppb [histamine] versus
5.4 +/- 2.1 ppb [HS], p = 0.4) or in Protocol 2 (7.9 +/- 4.7 ppb [histamine], 8.3
+/- 5.2 ppb [AMP], and 7.2 +/- 3.7 ppb [IS], p = 0.7). A significant reduction in
exhaled NO was observed directly after HS (mean +/- SEM: 39.2 +/- 3.9 %fall) and
AMP challenge (32.3 +/- 7.3 %fall) (MANOVA, p < 0.001), respectively, whereas
exhaled NO levels tended to decrease after histamine challenge. Isotonic saline
challenge did not induce changes in exhaled NO (p = 0.7). There was a positive
correlation between %fall in FEV1 and the %fall in exhaled NO after histamine,
HS, and AMP challenge as indicated by the mean slope of the within-subject
regression lines (p <= 0.04). We conclude that acute bronchoconstriction, as
induced by direct and indirect stimuli, is associated with a reduction in exhaled
NO levels in asthmatic subjects. This suggests that airway caliber should be
taken into account when monitoring exhaled NO in asthma.
PMID- 9655747
TI - Update: future directions for research on diseases of the lung. The American
Thoracic Society.
PMID- 9655748
TI - International guidelines for the selection of lung transplant candidates. The
American Society for Transplant Physicians (ASTP)/American Thoracic
Society(ATS)/European Respiratory Society(ERS)/International Society for Heart
and Lung Transplantation(ISHLT).
PMID- 9655749
TI - Fifty years of the Journal of Applied Physiology.
PMID- 9655750
TI - Invited editorial on "Pennes' 1948 paper revisited".
PMID- 9655751
TI - Pennes' 1948 paper revisited.
AB - A paper published by Harry H. Pennes in Volume 1 of the Journal of Applied
Physiology defined the theoretical basis for a considerable body of analysis
performed by many investigators during the ensuing half century. However, during
the past decade, the Pennes' model of heat transfer in perfused tissue has been
criticized for various reasons, one of which is that his own experimental data
seemed to be at variance with the model. More specifically, the shape of the mean
temperature-depth relationship measured by Pennes was distinctly different from
the shape of the theoretical curve. In this paper, I show that Pennes used an
inappropriate procedure to analyze his data and that, when the data are analyzed
in a more rigorous manner, they support his theory. Additional support for
Pennes' theory is provided by the experimental data of H. Barcroft and O. G.
Edholm [J. Physiol. (Lond.) 102: 5-20, 1942 and 104: 366-376, 1946], who had
previously studied cooling of the forearm during immersion in water at various
temperatures.
PMID- 9655752
TI - Wallace Fenn and the Journal of Applied Physiology.
PMID- 9655753
TI - My affair with the JAP.
PMID- 9655754
TI - Functional diameters of alveolar microvessels at high lung volume in zone II.
AB - To estimate the functional diameter of alveolar microvessels, we perfused
isolated rat lungs with fluorescent latex particles (1 diameter/lung) at
inflation, pulmonary arterial, and left atrial pressures of 25, 30, and 0 cmH2O,
respectively. We used confocal microscopy to count latex particles within septal
microvessels and flow cytometry to count particle concentrations in venous
outflow. We found 1-, 2-, and 4-micron-diameter particles within septal vessels
of 45 +/- 12, 31 +/- 12, and 25 +/- 9%, respectively, of examined alveoli.
Particles of 5-micron diameter were absent from septal vessels but were present
within a small percentage of corner vessels. Particle concentrations in the
venous outflow for 1-, 2-, 4-, and 5-micron-diameter particles were 54 +/- 28, 67
+/- 32, 2.2 +/- 0.3, and 0.4 +/- 0.3%, respectively, of the arterial inflow.
Particles with diameters of 6 or 10 micron were absent from venous outflow. Our
results suggest that, under these conditions, the functional diameter of the
septal microvessels is approximately 4 micron and that the diameter of the
adjacent corner vessels is slightly larger but <6 micron.
PMID- 9655755
TI - Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude
cerebral edema.
AB - The mechanism by which hypoxia causes high-altitude cerebral edema (HACE) is
unknown. Tissue hypoxia triggers angiogenesis, initially by expressing vascular
endothelial growth factor (VEGF), which has been shown to increase extracerebral
capillary permeability. This study investigated brain VEGF expression in 32 rats
exposed to progressively severe normobaric hypoxia (9-6% O2) for 0 (control), 3,
6, or 12 h or 1, 2, 3, or 6 days. O2 concentration was adjusted intermittently to
the limit of tolerance by activity and intake, but no attempt was made to detect
HACE. Northern blot analysis demonstrated that two molecular bands of transcribed
VEGF mRNA (approximately 3.9 and 4.7 kb) were upregulated in cortex and
cerebellum after as little as 3 h of hypoxia, with a threefold increase peaking
at 12-24 h. Western blot revealed that VEGF protein was increased after 12 h of
hypoxia, reaching a maximum in approximately 2 days. The expression of flt-1 mRNA
was enhanced after 3 days of hypoxia. We conclude that VEGF production in hypoxia
is consistent with the hypothesis that angiogenesis may be involved in HACE.
PMID- 9655756
TI - E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions.
AB - The objectives of this research were to determine the contribution of excitation
contraction (E-C) coupling failure to the decrement in maximal isometric tetanic
force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric
contractions and to elucidate possible mechanisms. The left anterior crural
muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric
contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture
forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and
intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured
and contralateral control EDL muscles at various times after injury up to 14
days. On the basis of the disproportional reduction in Po (approximately 51%)
compared with caffeine-induced force (approximately 11-21%), we estimate that E-C
coupling failure can explain 57-75% of the Po decrement from 0 to 5 days
postinjury. Comparable reductions in Po and K+-induced force (51%), and minor
reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C
coupling defect site is located at the t tubule-SR interface immediately after
injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was
elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol
induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4
chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased
SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease
in Po during the first several days after injury primarily stems from a failure
in the E-C coupling process.
PMID- 9655757
TI - Reduced leg blood flow during dynamic exercise in older endurance-trained men.
AB - It is currently unclear whether aging alters the perfusion of active muscles
during large-muscle dynamic exercise in humans. To study this issue, direct
measurements of leg blood flow (femoral vein thermodilution) and systemic
arterial pressure during submaximal cycle ergometry (70, 140, and 210 W) were
compared between six younger (Y; 22-30 yr) and six older (O; 55-68 yr)
chronically endurance-trained men. Whole body O2 uptake, ventilation, and
arterial and femoral venous samples for blood-gas, catecholamine, and lactate
determinations were also obtained. Training duration (min/day), estimated leg
muscle mass (dual-energy X-ray absorptiometry; Y, 21.5 +/- 1.2 vs. O, 19.9 +/-
0.9 kg), and blood hemoglobin concentration (Y, 14.9 +/- 0.4 vs. O, 14.7 +/- 0.2
g/dl) did not significantly differ (P > 0.05) between groups. Leg blood flow, leg
vascular conductance, and femoral venous O2 saturation were approximately 20-30%
lower in the older men at each work rate (all P < 0.05), despite similar levels
of whole body O2 uptake. At 210 W, leg norepinephrine spillover rates and femoral
venous lactate concentrations were more than twofold higher in the older men.
Pulmonary ventilation was also higher in the older men at 140 (+24%) and 210
(+39%) W. These results indicate that leg blood flow and vascular conductance
during cycle ergometer exercise are significantly lower in older endurance
trained men in comparison to their younger counterparts. The mechanisms
responsible for this phenomenon and the extent to which they operate in other
groups of older subjects deserve further attention.
PMID- 9655758
TI - Peak power output is maintained in rabbit psoas and rat soleus single muscle
fibers when CTP replaces ATP.
AB - The chemomechanical coupling mechanism in striated muscle contraction was
examined by changing the nucleotide substrate from ATP to CTP. Maximum shortening
velocity [extrapolation to zero force from force-velocity relation (Vmax) and
slope of slack test plots (V0)], maximum isometric force (Po), power, and the
curvature of the force-velocity curve [a/Po (dimensionless parameter inversely
related to the curvature)] were determined during maximum Ca2+-activated isotonic
contractions of fibers from fast rabbit psoas and slow rat soleus muscles by
using 0.2 mM MgATP, 4 mM MgATP, 4 mM MgCTP, or 10 mM MgCTP as the nucleotide
substrate. In addition to a decrease in the maximum Ca2+-activated force in both
fiber types, a change from 4 mM ATP to 10 mM CTP resulted in a decrease in Vmax
in psoas fibers from 3.26 to 1.87 muscle length/s. In soleus fibers, Vmax was
reduced from 1.94 to 0.90 muscle length/s by this change in nucleotide.
Surprisingly, peak power was unaffected in either fiber type by the change in
nucleotide as the result of a three- to fourfold decrease in the curvature of the
force-velocity relationship. The results are interpreted in terms of the Huxley
model of muscle contraction as an increase in f1 and g1 coupled to a decrease in
g2 (where f1 is the rate of cross-bridge attachment and g1 and g2 are rates of
detachment) when CTP replaces ATP. This adequately accounts for the observed
changes in Po, a/Po, and Vmax. However, the two-state Huxley model does not
explicitly reveal the cross-bridge transitions that determine curvature of the
force-velocity relationship. We hypothesize that a nucleotide-sensitive
transition among strong-binding cross-bridge states following Pi release, but
before the release of the nucleotide diphosphate, underlies the alterations in
a/Po reported here.
PMID- 9655759
TI - Thermogenesis in newborn rats after prenatal or postnatal hypoxia.
AB - Oxygen consumption (VO2) was measured in normoxia as ambient temperature (Ta) was
lowered from 40 to 15 degrees C, at the rate of 0.5 degrees C/min
(thermoneutrality approximately 33 degrees C). In 2-day-old rats born in hypoxia
after hypoxic gestation, the Ta-VO2 relationship was as in controls; their
interscapular brown adipose tissue (IBAT) was hypoplastic (less proteins and
DNA), with lower concentration of the mitochondrial uncoupling protein
thermogenin. In 8-day-old rats exposed to hypoxia postnatally (day 2 to day 8),
at any Ta below thermoneutrality VO2 was higher than in controls; also, in this
group IBAT was hypoplastic with decreased thermogenin. Additional measurements
under various experimental conditions indicated that the increased thermogenic
capacity was not explained by the smaller body mass and increased blood oxygen
content or by the eventuality of intermittent cold stimuli during the chronic
hypoxia. On the other hand, chronic hypercapnia (3% CO2 in normoxia, from day 2
to day 8) also resulted in increased normoxic thermogenesis. We conclude that
chronic hypoxia in the perinatal period 1) reduces IBAT mass and thermogenin
concentration and 2) can increase the newborn's thermogenic capacity because of
stress-related mechanisms not specific to hypoxia.
PMID- 9655760
TI - Dissociation between hysteresivity and tension in constricted tracheal and
parenchymal strips.
AB - The object of this study was to investigate how changes in the contractile state
of smooth muscle would modify oscillatory mechanics of tracheal muscle and lung
parenchyma during agonist challenge. Guinea pig tracheal and parenchymal lung
strips were suspended in an organ bath. Measurements of length (L) and tension
(T) were recorded during sinusoidal oscillations under baseline conditions and
after challenge with 1 mM ACh. Measurements were also obtained in strips
pretreated with the calmodulin inhibitor calmidazolium (Cmz) or staurosporine
(Stauro), a protein kinase C inhibitor. Elastance (E) and resistance (R) were
calculated by fitting changes in T, L, and DeltaL/Deltat to the equation of
motion. Hysteresivity (eta) was obtained from the following equation: eta =
(R/E)2pif, where f is frequency. Finally, maximal unloaded shortening velocity
during electrical field stimulation was measured in Cmz-pretreated and control
tracheal strips. In tracheal strips, pretreatment with Cmz caused a significant
decrease in the eta response to ACh challenge and in maximal unloaded shortening
velocity measured during electrical field stimulation; Stauro decreased the T, E,
and R response to ACh. In parenchymal strips, Cmz decreased the eta response,
whereas Stauro had no effect. These results suggest that modifications in the
contractile state of the smooth muscle are reflected in changes in the hysteretic
behavior and that T and eta may be controlled independently. Second, inasmuch as
changes in eta were similar in parenchymal and tracheal strips, the contractile
element is implicated as the structure responsible for constriction-induced
changes in the mechanical behavior of the lung periphery.
PMID- 9655761
TI - Differences in rat skeletal muscles after incline and decline running.
AB - Rats were trained for 5 days by running on either an inclined or declined
treadmill. Three days later, the rats were anesthetized, and angle-torque curves
were plotted for the vastus intermedius muscles. The maximum active torque was
generated at significantly greater muscle lengths for muscles from decline
trained rats compared with incline-trained rats. Sixteen muscles were then fixed
and acid digested, and fiber lengths and sarcomere lengths were measured. The
estimated average number of sarcomeres in series was greater in muscle fibers
from decline-trained animals. Fourteen other muscles underwent a test series of
lengthening contractions, all from the same knee angle. Torque fell less and the
optimum angle shifted less for muscles from decline-trained animals, showing that
the decline-trained muscles were more resistant to changes in mechanical
parameters that indicate damage. These results support but do not prove the
proposal that the lesser damage from a series of eccentric contractions seen in
muscles trained by prior eccentric contractions is due to a greater number of
sarcomeres in series.
PMID- 9655762
TI - Catecholaminergic modulation of respiratory rhythm in an in vitro turtle brain
stem preparation.
AB - An in vitro brain stem preparation from adult turtles was used to determine
effects of dopamine (DA) and norepinephrine (NE) on the pattern of respiratory
motor output recorded from hypoglossal nerve roots (XII). Bath-applied DA (10-200
microM) increased the frequency of respiratory bursts (peaks) from 0.9 +/- 0.2 to
2.4 +/- 0.3 (SE) peaks/min, resulting in a 99 +/- 9% increase in neural minute
activity. R[+]-SCH-23390 (10 microM, D1 antagonist) and eticlopride (20 microM,
D2 antagonist) attenuated the DA-mediated increase in peak frequency by 52 and
59%, respectively. On the other hand, the DA-receptor agonists apomorphine (D1,
D2), quinelorane (D2), and SKF-38393 (D1) had no effect on peak frequency.
Prazosin, an alpha1-adrenergic antagonist (250 nM) abolished the DA-mediated
frequency increase. Although NE (10-200 microM) and phenylephrine (10-200 microM,
alpha1-adrenergic agonist) increased peak frequency from 0.5 +/- 0.1 to 1.2 +/-
0.3 peaks/min and from 0.6 +/- 0.1 to 1. 0 +/- 0.2 peaks/min, respectively, these
effects were not as large as that with DA alone. The data suggest that both
dopaminergic and adrenergic receptor activation in the brain stem increase
respiratory frequency in turtles, but the DA receptor-mediated increase is
dependent on coactivation of alpha1-adrenergic receptors.
PMID- 9655763
TI - Cadaver validation of skeletal muscle measurement by magnetic resonance imaging
and computerized tomography.
AB - Magnetic resonance imaging (MRI) and computerized tomography (CT) are promising
reference methods for quantifying whole body and regional skeletal muscle mass.
Earlier MRI and CT validation studies used data-acquisition techniques and data
analysis procedures now outdated, evaluated anatomic rather than adipose tissue
free skeletal muscle (ATFSM), studied only the relatively large thigh, or found
unduly large estimation errors. The aim of the present study was to compare arm
and leg ATFSM cross-sectional area estimates (cm2) by using standard MRI and CT
acquisition and image-analysis methods with corresponding cadaver estimates. A
second objective was to validate MRI and CT measurements of adipose tissue
embedded within muscle (interstitial adipose tissue) and surrounding muscle
(subcutaneous adipose tissue). ATFSM area (n = 119) by MRI [38.9 +/- 22.3 (SD)
cm2], CT (39.7 +/- 22.8 cm2), and cadaver (39.5 +/- 23.0 cm2) were not different
(P > 0.001), and both MRI and CT estimates of ATFSM were highly correlated with
corresponding cadaver values [MRI: r = 0.99, SE of estimate (SEE) 3.9 cm2, P <
0.001; and CT: r = 0.99, SEE = 3.8 cm2, P < 0.001]. Similarly good results were
observed between MRI- and CT-measured vs. cadaver-measured interstitial and
subcutaneous adipose tissue. For MRI-ATFSM the intraobserver correlation for
duplicate measurements in vivo was 0. 99 [SEE = 8.7 cm2 (2.9%), P < 0.001]. These
findings strongly support the use of MRI and CT as reference methods for
appendicular skeletal muscle, interstitial and subcutaneous adipose tissue
measurement in vivo.
PMID- 9655764
TI - Asymmetry in reflex responses of nasal muscles in anesthetized guinea pigs.
AB - Nasal reflexes elicited by mechanical or electrical stimulation of nasal
afferents were studied in anesthetized guinea pigs. Probing the nasal cavity of
one side evoked a greater activation of the contralateral than the ipsilateral
nasal muscles and, occasionally, sneezing. Similarly, electrical stimulation of
the ethmoidal nerve often caused sneezing, with a greater activation of the nasal
muscles and a greater increase in resistance on the contralateral side.
Asymmetrical activation of the nasal muscles in response to mechanical stimuli
induces asymmetrical airflows, especially during sneezing, between the two sides
of the nasal cavity. Most of the expired air is forcibly blown out through the
ipsilateral nostril, thus improving the elimination of irritants from the nose.
PMID- 9655765
TI - Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat:
putative role of nitric oxide.
AB - In humans, the hypoxic ventilatory response (HVR) is augmented when preceded by a
short hyperoxic exposure (Y. Honda, H. Tani, A. Masuda, T. Kobayashi, T. Nishino,
H. Kimura, S. Masuyama, and T. Kuriyama. J. Appl. Physiol. 81: 1627-1632, 1996).
To examine whether neuronal nitric oxide synthase (nNOS) is involved in such
hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult rats underwent
hypoxic challenges (10% O2-5% CO2-balance N2) preceded either by 10 min of room
air (-O2) or of 100% O2 (+O2). At least 48 h later, similar challenges were
performed after the animals received the selective nNOS inhibitor 7-nitroindazole
(25 mg/kg ip). In -O2 runs, minute ventilation (VE) increased from 121.3 +/- 20.5
(SD) ml/min in room air to 191.7 +/- 23.8 ml/min in hypoxia (P < 0.01). After
+O2, VE increased from 114.1 +/- 19.8 ml/min in room air to 218.4 +/- 47. 0
ml/min in hypoxia (+O2 vs. -O2: P < 0.005, ANOVA). After 7-nitroindazole
administration, HVR was not affected in the -O2 treatment group with VE
increasing from 113.7 +/- 17.8 ml/min in room air to 185.8 +/- 35.0 ml/min in
hypoxia (P < 0.01). However, HVR potentiation in +O2-exposed animals was
abolished (111.8 +/- 18. 0 ml/min in room air to 184.1 +/- 35.6 ml/min in
hypoxia; +O2 vs. -O2: P not significant). We conclude that in the conscious rat
nNOS activation mediates essential components of the HVR potentiation elicited by
a previous short hyperoxic exposure.
PMID- 9655766
TI - Glycogen supercompensation masks the effect of a traininginduced increase in GLUT
4 on muscle glucose transport.
AB - Endurance exercise training induces a rapid increase in the GLUT-4 isoform of the
glucose transporter in muscle. In fasted rats, insulin-stimulated muscle glucose
transport is increased in proportion to the increase in GLUT-4. There is evidence
that high muscle glycogen may decrease insulin-stimulated glucose transport. This
study was undertaken to determine whether glycogen supercompensation interferes
with the increase in glucose transport associated with an exercise-induced
increase in GLUT-4. Rats were trained by means of swimming for 6 h/day for 2
days. Rats fasted overnight after the last exercise bout had an approximately
twofold increase in epitrochlearis muscle GLUT-4 and an associated approximately
twofold increase in maximally insulin-stimulated glucose transport activity.
Epitrochlearis muscles of rats fed rodent chow after exercise were glycogen
supercompensated (86.4 +/- 4.8 micromol/g wet wt) and showed no significant
increase in maximally insulin-stimulated glucose transport above the sedentary
control value despite an approximately twofold increase in GLUT-4. Fasting
resulted in higher basal muscle glucose transport rates in both sedentary and
trained rats but did not significantly increase maximally insulin-stimulated
transport in the sedentary group. We conclude that carbohydrate feeding that
results in muscle glycogen supercompensation prevents the increase in maximally
insulin-stimulated glucose transport associated with an exercise training-induced
increase in muscle GLUT-4.
PMID- 9655767
TI - Spaceflight modulates insulin-like growth factor binding proteins and
glucocorticoid receptor in osteoblasts.
AB - Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission.
After 20-h treatment with 1alpha,25-dihydroxyvitamin D3, conditioned media were
harvested and cellular DNA and/or RNA were fixed on board. The insulin-like
growth factor binding protein (IGF BP)-3 levels in the media were three- and
tenfold higher than in ground controls on the fourth and fifth flight days, as
quantitated by Western ligand blotting and radioimmunoassay, respectively. The
increased IGF BP-3 protein levels correlated with two- to threefold elevation of
IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain
reaction. The IGF BP-5 mRNA levels in flight cultures were 33-69% lower than in
ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than
in ground controls on the fifth day but were not different on the fourth day. The
glucocorticoid receptor mRNA levels in flight cultures were increased by three-
to eightfold on the fourth and fifth days compared with levels in ground
controls. These data suggest potential mechanisms underlying spaceflight-induced
osteopenia.
PMID- 9655768
TI - Human skeletal muscle carnitine palmitoyltransferase I activity determined in
isolated intact mitochondria.
AB - This study was designed to compare the activity of skeletal muscle carnitine
palmitoyltransferase I (CPT I) in trained and inactive men (n = 14) and women (n
= 12). CPT I activity was measured in intact mitochondria, isolated from needle
biopsy vastus lateralis muscle samples ( approximately 60 mg). The variability of
CPT I activity determined on two biopsy samples from the same leg on the same day
was 4.4, whereas it was 7.0% on two biopsy samples from the same leg on different
days. The method was sensitive to the CPT I inhibitor malonyl-CoA (88%
inhibition) and therefore specific for CPT I activity. The mean CPT I activity
for all 26 subjects was 141.1 +/- 10.6 micromol . min-1 . kg wet muscle (wm)-1
and was not different when all men vs. all women (140.5 +/- 15.7 and 142.2 +/-
14.5 micromol . min-1 . kg wm-1, respectively) were compared. However, CPT I
activity was significantly higher in trained vs. inactive subjects for both men
(176.2 +/- 21.1 vs. 104.1 +/- 13.6 micromol . min-1 . kg wm-1) and women (167.6
+/- 14.1 vs. 91.2 +/- 9.5 micromol . min-1 . kg wm-1). CPT I activity was also
significantly correlated with citrate synthase activity (all subjects, r = 0.76)
and maximal oxygen consumption expressed in milliliters per kilogram per minute
(all subjects, r = 0.69). The results of this study suggest that CPT I activity
can be accurately and reliably measured in intact mitochondria isolated from
human muscle biopsy samples. CPT I activity was not affected by gender, and
higher activities in aerobically trained subjects appeared to be the result of
increased mitochondrial content in both men and women.
PMID- 9655769
TI - Effects of caffeine on blood pressure, heart rate, and forearm blood flow during
dynamic leg exercise.
AB - This study examined the acute effects of caffeine on the cardiovascular system
during dynamic leg exercise. Ten trained, caffeine-naive cyclists (7 women and 3
men) were studied at rest and during bicycle ergometry before and after the
ingestion of 6 mg/kg caffeine or 6 mg/kg fructose (placebo) with 250 ml of water.
After consumption of caffeine or placebo, subjects either rested for 100 min
(rest protocol) or rested for 45 min followed by 55 min of cycle ergometry at 65%
of maximal oxygen consumption (exercise protocol). Measurement of mean arterial
pressure (MAP), forearm blood flow (FBF), heart rate, skin temperature, and
rectal temperature and calculation of forearm vascular conductance (FVC) were
made at baseline and at 20-min intervals. Plasma ANG II was measured at baseline
and at 60 min postingestion in the two exercise protocols. Before exercise,
caffeine increased both systolic blood pressure (17%) and MAP (11%) without
affecting FBF or FVC. During dynamic exercise, caffeine attenuated the increase
in FBF (53%) and FVC (50%) and accentuated exercise-induced increases in ANG II
(44%). Systolic blood pressure and MAP were also higher during exercise plus
caffeine; however, these increases were secondary to the effects of caffeine on
resting blood pressure. No significant differences were observed in heart rate,
skin temperature, or rectal temperature. These findings indicate that caffeine
can alter the cardiovascular response to dynamic exercise in a manner that may
modify regional blood flow and conductance.
PMID- 9655770
TI - Effects of posture on cardiovascular responses to lower body positive pressure at
rest and during dynamic exercise.
AB - We tested the hypothesis that cardiovascular responses to lower body positive
pressure (LBPP) would be dependent on the posture of the subject and also on the
background condition (rest or exercise). We measured heart rate (HR), mean
arterial blood pressure (MAP), and cardiac stroke volume in eight subjects at
rest and during cycle ergometer exercise (76 +/- 3 W) with and without LBPP (25,
50, and 75 mmHg) in the supine and upright positions. At rest, the increase in
MAP was proportional to the increase in LBPP and was greater in the supine (6 +/-
2, 15 +/- 3, and 26 +/- 3 mmHg) than in the upright (2 +/- 3, 9 +/- 3, and 17 +/-
3 mmHg) position. During dynamic exercise, the increases in MAP evoked by 25, 50,
and 75 mmHg LBPP were greater in the supine (13 +/- 2, 28 +/- 3, and 40 +/- 3
mmHg) than in the upright (7 +/- 3, 12 +/- 3, and 25 +/- 3 mmHg) position. We
conclude that the systemic pressure response to LBPP is clearly dependent on the
body position, with the larger pressure responses being associated with the
supine position both at rest and during dynamic leg exercise.
PMID- 9655771
TI - Exercise training enhances adrenergic constriction and dilation in the rat
spinotrapezius muscle.
AB - Treadmill training increases functional vasodilation in the rat spinotrapezius
muscle, although there is no acute increase in blood flow and no increase in
oxidative capacity. To assess concurrent changes in vascular reactivity, we
measured arterial diameters in the spinotrapezius muscle of sedentary (Sed) and
treadmill-trained (Tr; 9-10 wk; terminal intensity 30 m/min, 1.5 degrees incline,
for 90 min) rats during iontophoretic application of norepinephrine, epinephrine
(Epi), and H+ (HCl) and during superfusion with adenosine. Terminal-feed arteries
and first-order arterioles in Tr rats constricted more than those in Sed rats at
the higher current doses of norepinephrine and Epi. In contrast, at low-current
doses of Epi, first- and second-order arterioles dilated in Tr but not in Sed
rats. The vascular responses to HCl were highly variable, but second-order
arterioles of Tr rats constricted more than those of Sed rats at intermediate
current doses. There were no significant differences between Sed and Tr rats in
the vascular responses to adenosine. Both adrenergic vasodilation and
vasoconstriction were enhanced in the spinotrapezius muscle of Tr rats, and
enhanced adrenergic vasodilation may contribute to increased functional
vasodilation. These observations further demonstrate vascular adaptations in
"nontrained" skeletal muscle tissues.
PMID- 9655772
TI - Thermoregulatory reflexes and cutaneous active vasodilation during heat stress in
hypertensive humans.
AB - During dynamic exercise in the heat, increases in skin blood flow are attenuated
in hypertensive subjects when compared with normotensive subjects. We studied
responses to passive heat stress (water-perfused suits) in eight hypertensive and
eight normotensive subjects. Forearm blood flow was measured by venous-occlusion
plethysmography, mean arterial pressure (MAP) was measured by Finapres, and
forearm vascular conductance (FVC) was calculated. Bretylium tosylate (BT)
iontophoresis was used to block active vasoconstriction in a small area of skin.
Skin blood flow was indexed by laser-Doppler flowmetry at BT-treated and
untreated sites, and cutaneous vascular conductance was calculated. In
normothermia, FVC was lower in hypertensive than in normotensive subjects (P <
0.01). During heat stress, FVC rose to similar levels in both groups (P > 0.80);
concurrent cutaneous vascular conductance increases were unaffected by BT
treatment (P > 0.60). MAP was greater in hypertensive than in normotensive
subjects during normothermia (P < 0.05, hypertensive vs. normotensive subjects).
During hyperthermia, MAP fell in hypertensive subjects but showed no
statistically significant change in normotensive subjects (P < 0.05, hypertensive
vs. normotensive subjects). The internal temperature at which vasodilation began
did not differ between groups (P > 0.80). FVC is reduced during normothermia in
unmedicated hypertensive subjects; however, they respond to passive heat stress
in a fashion no different from normotensive subjects.
PMID- 9655773
TI - Catecholamine effects on lipolysis and blood flow in human abdominal and femoral
adipose tissue.
AB - With the use of the microdialysis method, the present study, performed on young,
healthy, nonobese subjects of both genders, compares the effects of locally
infused catecholamines on glycerol concentration and blood flow in abdominal
(Abd) and femoral (Fem) adipose tissue. Physiological activation of the
sympathetic nervous system through active tilt was also investigated. In both
genders, extracellular glycerol concentration was higher in Fem than in Abd
adipose tissue. Local blood flow was lower in Fem than in Abd adipose tissue.
Isoproterenol perfusion increased extracellular glycerol levels, but no
differences were found by gender or fat-deposit site. Isoproterenol induced a
greater increase in local blood flow in Fem adipose tissue in both genders.
Epinephrine and norepinephrine perfusion increased extracellular glycerol and
reduced blood flow. No major differences were found according to gender and fat
deposit site. Active tilt increased plasma glycerol, free fatty acid,
norepinephrine levels, and extracellular glycerol concentration to the same
extent whatever the gender and fat deposit. Thus, Fem adipose tissue is
characterized by a higher extracellular glycerol concentration and a lower blood
flow than is Abd tissue in men and women. In these tissues, in situ lipolysis and
local blood flow were similar in response to adrenergic stimulation.
PMID- 9655774
TI - IGF-I and/or growth hormone preserve diaphragm fiber size with moderate
malnutrition.
AB - Resistance to the anabolic effects of growth hormone (GH) occurs with severe
caloric deficit. This study examined whether moderate caloric deficit (50% of
daily intake for 7 days) in the adolescent rat exceeds a critical threshold for
GH action and whether a combination of GH and insulin-like growth factor I (IGF
I) would have enhanced anabolic effects on the diaphragm (Dia). Five groups of
rats (4 wk old) were studied: 1) control (Ctl), 2) nutritionally deprived (ND),
3) ND + GH, 4) ND + IGF-I, and 5) ND + GH + IGF-I. IGF-I was given by continuous
infusion (200 microg/day). GH was injected subcutaneously (250 microg every 12
h). Contractile and fatigue properties of the Dia were determined in vitro.
Quantitative histochemical methods were used to determine Dia fiber type
proportions, cross-sectional areas, and succinate dehydrogenase activities. The
body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas
that of ND rats receiving growth factors was intermediate. Serum IGF-I levels
were reduced 54% in ND animals and maintained with the provision of growth
factors. Dia fatigue resistance was improved in ND animals receiving growth
factors. There were no differences in Dia contractile properties, fiber type
proportions, or succinate dehydrogenase activities across groups. ND resulted in
atrophy/growth arrest of all Dia fibers (20-32%) compared with Ctl.
Administration of IGF-I and/or GH completely prevented atrophy/growth arrest of
all Dia fibers. No additive or synergistic effects were noted. We propose that
these growth factors may provide useful short-term adjunctive nutritional support
in circumstances in which the provision of optimal nutrition may be delayed or
inadequate.
PMID- 9655775
TI - Rib cage muscle interaction in airway pressure generation.
AB - We have previously demonstrated in dogs that the change in airway opening
pressure (DeltaPao) produced by isolated maximum activation of the parasternal
intercostal or triangularis sterni muscle in a single interspace, the
sternomastoids, and the scalenes is proportional to the product of muscle mass
and the fractional change in muscle length per unit volume increase of the
relaxed chest wall. In the present study, we have assessed the interactions
between these muscles by comparing the DeltaPao obtained during simultaneous
activation of a pair of muscles (measured DeltaPao) to the sum of the DeltaPao
values obtained during their separate activation (predicted DeltaPao). Measured
and predicted DeltaPao values were compared for the following pairs of muscles:
the parasternal intercostals in two interspaces, the parasternal intercostals in
one interspace and either the sternomastoids or the scalenes, two segments of the
triangularis sterni, and the interosseous intercostals in two contiguous
interspaces. For all these pairs, the measured DeltaPao was within approximately
10% of the predicted value. We therefore conclude that 1) the pressure changes
generated by the rib cage muscles are essentially additive; and 2) measurements
of the mass of a particular muscle and of its fractional change in length during
passive inflation can be used to estimate the potential pressure-generating
ability of the muscle during coordinated activity as well as during isolated
activation.
PMID- 9655776
TI - Human thermoregulatory responses during serial cold-water immersions.
AB - This study examined whether serial cold-water immersions over a 10-h period would
lead to fatigue of shivering and vasoconstriction. Eight men were immersed (2 h)
in 20 degrees C water three times (0700, 1100, and 1500) in 1 day (Repeat). This
trial was compared with single immersions (Control) conducted at the same times
of day. Before Repeat exposures at 1100 and 1500, rewarming was employed to
standardize initial rectal temperature. The following observations were made in
the Repeat relative to the Control trial: 1) rectal temperature was lower and
heat debt was higher (P < 0.05) at 1100; 2) metabolic heat production was lower
(P < 0.05) at 1100 and 1500; 3) subjects perceived the Repeat trial as warmer at
1100. These data suggest that repeated cold exposures may impair the ability to
maintain normal body temperature because of a blunting of metabolic heat
production, perhaps reflecting a fatigue mechanism. An alternative explanation is
that shivering habituation develops rapidly during serially repeated cold
exposures.
PMID- 9655777
TI - Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity.
AB - Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from
emphysema and chronic obstructive pulmonary disease. This effect may result as a
consequence of the physiological derangements because of the emphysema condition
or, alternatively, as a consequence of the reduced physical activity level in
these patients. To explore this issue, citrate synthase (CS) activity was
measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters
6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase
[emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was
monitored, and no difference between groups was found. Excised lung volume
increased with emphysema (Con, 1.5 +/- 0.3 g; Emp, 3.0 +/- 0.3 g, P < 0.002).
Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 +/-
2.0; Emp, 39.2 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) and vastus
lateralis (Con, 48.5 +/- 1.5; Emp, 44.9 +/- 0.8 micromol . min-1 . g wet wt-1, P
< 0.05) but not in the plantaris (Con, 47.4 +/- 3.9; Emp, 48.0 +/- 2.1 micromol .
min-1 . g wet wt-1, P < 0.05) muscle. In contrast, CS activity increased in the
costal (Con, 61.1 +/- 1.8; Emp, 65.1 +/- 1.5 micromol . min-1 . g wet wt-1, P <
0.05) and crural (Con, 58.5 +/- 2.0; Emp, 65.7 +/- 2.2 micromol . min-1 . g wet
wt-1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per
se can induce decrements in the oxidative capacity of certain nonventilatory
skeletal muscles that may contribute to exercise limitations in the emphysematous
patient.
PMID- 9655778
TI - Long-term effects of clenbuterol on diaphragm morphology and contractile
properties in emphysematous hamsters.
AB - The aim of the present study was to investigate the effect of chronic long-term
clenbuterol treatment (1 mg/kg subcutaneously twice a day for 12 wk) on diaphragm
morphology and function in emphysematous (EH) and normal hamsters (NH).
Clenbuterol increased body weight, diaphragm weight, and skeletal muscle weight
in both EH and NH to a similar extent. In the diaphragm, clenbuterol
significantly increased myosin heavy chain type I, IIa, and IIx muscle fiber
cross-sectional areas by approximately 35-55% in both EH and NH. This response to
clenbuterol treatment was not significantly different between EH and NH
diaphragm. In EH, twitch force (Pt), maximal tetanic force, and force-frequency
curve were significantly reduced compared with NH. In EH, clenbuterol increased
Pt by approximately 10%, restoring Pt to NH level. A similar improvement was
observed in the force-frequency characteristics. Clenbuterol did not alter
contractile properties in NH. In conclusion, long-term clenbuterol treatment
resulted in an increased size of all diaphragm muscle fiber types in both NH and
EH. Clenbuterol completely abolished the reduced force generation induced by
emphysema.
PMID- 9655779
TI - Direct measurement of the energy expenditure of physical activity in preterm
infants.
AB - The energy cost of physical activity (EEA) has been estimated to account for 5
17% of total energy expenditure (TEE) in neonates. To directly measure EEA, a
force plate was developed and validated to measure work outputs ranging from 0.3
to 40 kcal . kg-1 . day-1. By use of this force plate plus indirect calorimetry,
TEE and EEA were measured and correlated with five activity states in 24 infants
with gestational age of 31.6 +/- 0.5 (SE) wk and postnatal age of 24.8 +/- 3.7
days. TEE and EEA were 69.2 +/- 1.5 and 2.4 +/- 0.2 kcal . kg-1 . day-1,
respectively. EEA per state was 0.5 +/- 0.0 (quiet sleep), 2.4 +/- 0.2 (active
sleep), 2.8 +/- 0.4 (quiet awake), 7.5 +/- 0.8 (active awake), and 15.1 +/- 2.3
(crying) kcal . kg-1 . day-1. This provides the first direct measurement of the
contribution of physical activity to TEE in preterm infants and will enable
measurement of caloric expenditure from muscle activity in various disease
conditions and development of nursing strategies to minimize unnecessary energy
losses.
PMID- 9655780
TI - Airway-parenchymal interdependence after airway contraction in rat lung explants.
AB - The constriction of pulmonary airways is limited by the tethering effect exerted
by parenchymal attachments. To characterize this tethering effect at the scale of
intraparenchymal airways, we studied the pattern of parenchymal distortion due to
bronchoconstriction in a rat lung explant system. First, we measured the elastic
modulus under tension for 2% (wt/vol) agarose alone (37.6 +/- 1.5 kPa) and for
agarose-filled lung (5.7 +/- 1.3 kPa). The latter is similar to the elastic
modulus of air-filled lung at total lung capacity (4.5-6 kPa) (S. J. Lai-Fook, T.
A. Wilson, R. E. Hyatt, and J. R. Rodarte. J. Appl. Physiol. 40: 508-513, 1976),
suggesting that explants can be used as a model of lung tissue distortion.
Subsequently, confocal microscopic images of fluorescently labeled 0.5-mm-thick
explants prepared from agarose-filled rat lungs inflated to total lung capacity
(48 ml/kg) were acquired. Images were taken before and after airway constriction
was induced by direct application of 10 mM methacholine, and the pattern of
parenchymal distortion was measured from the displacement of tissue landmarks
identified in each image for 14 explants. The magnitude of the radial component
of tissue displacement was calculated as a function of distance from the airway
wall and characterized by a parameter, b, describing the rate at which tissue
movement decreased with radial distance. The parameter b was 0.994 +/- 0.19 (SE),
which is close to the prediction of b = 1 of micromechanical modeling (T. A.
Wilson. J. Appl. Physiol. 33: 472-478, 1972). There was significant variability
in b, however, which was correlated with the fractional reduction in airway
diameter (r = 0.496). Additionally, parenchymal distortion showed significant
torsion with respect to the radial direction. This torsion was similar in
concentric zones around the airway, suggesting that it originates from
inhomogeneity in the parenchyma rather than inhomogeneous airway constriction.
Our results demonstrate the significance of the nonlinear mechanical properties
of alveolar walls and the anisotropy of the parenchyma in determining the nature
of airway-parenchymal interdependence.
PMID- 9655781
TI - Comparisons of two-, three-, and four-compartment models of body composition
analysis in men and women.
AB - This study compared the traditional two-compartment (fat mass or FM; fat free
mass or FFM) hydrodensitometric method of body composition measurement, which is
based on body density, with three (FM, total body water or TBW, fat free dry
mass)- and four (FM, TBW, bone mineral mass or BMM, residual)-compartment models
in highly trained men (n = 12), sedentary men (n = 12), highly trained women (n =
12), and sedentary women (n = 12). The means and variances for the relative body
fat (%BF) differences between the two- and three-compartment models [2.2 +/- 1.6
(SD) % BF; n = 48] were significantly greater (P = 0.02) than those between the
three- and four-compartment models (0.2 +/- 0.3% BF; n = 48) for all four groups.
The three-compartment model is more valid than the two-compartment
hydrodensitometric model because it controls for biological variability in TBW,
but additional control for interindividual variability in BMM via the four
compartment model achieves little extra accuracy. The combined group (n = 48)
exhibited greater (P < 0.001) FFM densities (1.1075 +/- 0.0049 g/cm3) than the
hydrodensitometric assumption of 1.1000 g/cm3, which is based on analyses of
three male cadavers aged 25, 35, and 46 yr. This was primarily because their FFM
hydration (72.4 +/- 1.1%; n = 48) was lower (P = 0.001) than the
hydrodensitometric assumption of 73.72%.
PMID- 9655782
TI - Developmentally regulated expression of cytochrome-c oxidase isoforms in
regenerating rat skeletal muscle.
AB - The developmental expression of tissue-specific isoforms of cytochrome-c oxidase
(COX) subunit VIII [heart (COX VIII-H) and liver (COX VIII-L)] and the influence
of innervation were examined in regenerating fast [extensor digitorum longus
(EDL)] and slow (soleus) muscles. In adult muscles, COX VIII-H was the
predominant isoform. The COX VIII-L mRNA was expressed 3 days after induction of
regeneration, and it progressively decreased after 7, 10, 14, and 30 days of
regeneration in both muscles. In contrast, the expression of COX VIII-H mRNA
accumulated as myogenesis proceeded to the myotube stage between 7 and 10 days of
regeneration and progressively increased to near control levels by 30 days. The
influence of innervation on the expression of COX VIII and alpha-actin isoforms
was examined in control, innervated, and denervated regenerating muscles at 3 and
10 days. The relative expression of COX VIII-L mRNA in denervated regenerating
EDL muscles was significantly greater, while that of COX VIII-H was significantly
less than in innervated regenerating EDL muscles after 10 days of regeneration.
Similarly, cardiac alpha-actin mRNA levels were elevated in denervated
regenerating EDL muscles after 10 days of regeneration. In conclusion, motor
innervation influences the transition from the COX VIII-L to COX VIII-H isoform
during myogenesis in regenerating muscles.
PMID- 9655783
TI - Mechanical work of breathing during maximal voluntary ventilation.
AB - With the use of the esophageal balloon technique, the working capacity of the
respiratory muscles was assessed in four normal subjects by measuring the work
per breath (W) and respiratory power (W) during maximal voluntary ventilation
with imposed respiratory frequencies (f) ranging from 20 to 273 cycles/min.
Measurements were made in a body plethysmograph to assess the work wasted as a
result of alveolar gas compressibility (Wg'). In line with other types of human
voluntary muscle activity, W decreased with increasing f, whereas W exhibited a
maximum at f of approximately 100 cycles/min. Up to this f value, Wg' was small
relative to W. With further increase in f, the Wg'/W ratio increased
progressively, amounting to 8-22% of W at f of 200 cycles/min.
PMID- 9655784
TI - Long-range correlations of serial FEV1 measurements in emphysematous patients and
normal subjects.
AB - In obstructive lung disease the annual change in lung function is usually
estimated from serial measurements of forced expiratory volume in 1 s (FEV1).
Frequent measurements in each patient may not improve this estimate because data
are not statistically independent; i.e., the measurements are autocorrelated. The
purpose of this study was to describe the correlation structure in time series of
FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency
(phenotype PiZ) and moderate to severe emphysema and two subjects with normal
lungs were followed for several years with daily self-administered spirometry.
FEV1 measurements fulfilling standard criteria were detrended, and the
autocorrelation profile and the power spectrum were calculated. On average the
subjects were followed for >3 yr and performed >1,000 acceptable spirometries.
The autocorrelation of FEV1 measurements in the emphysematous patients was
approximately 0.35 for short intervals and decreased almost exponentially with a
half time of 38 days. Between 3 and 4 mo, the autocorrelation function became
negative. It reached a minimum of -0.1 at approximately 8 mo and then increased
toward zero over the following 12 mo. The autocorrelation function in the two
normal subjects showed a similar pattern, but with a faster decay toward zero. In
the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f
pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We
conclude that serial spirometric measurements show long-range correlations. The
practical implication is that FEV1 need not be measured more often than once
every 3 mo in studies of the long-term trends in lung function.
PMID- 9655785
TI - Meniscus formation during tracheal instillation of surfactant.
AB - The method of surfactant instillation into the lungs for treatment of neonatal
respiratory distress syndrome is an important attribute of delivery, and it may
determine the overall efficacy of treatment. Previous studies primarily focused
on the rate at which the bolus is instilled. These findings show that rapid
injections lead to a more homogenous distribution, whereas slow infusions drain
into the dependent lung with respect to gravity, resulting in a heterogeneous
deposition. These results suggest that it is beneficial to form a meniscus, from
which a more homogenous dispersal can proceed. The objective of the present study
was to develop a functional criterion for meniscus formation during bolus
injection. An in vitro experiment was used to examine the clinical setting of
surfactant instillation. The physical variables examined were the bolus viscosity
(mu) and density (rho), gravity (g), injection rate (Q), orientation of the
trachea with respect to gravity (theta), tracheal size (D), surface tension
(gamma), and catheter size (d). All quantities were varied, except gravity and
catheter size. Experimental results show that a meniscus will form when NSt > 0.
004Re2/3, where NSt is Stokes number and Re is Reynolds number, NSt =
muQ/D4rhogsintheta, a ratio of viscous effects to gravitational effects, and Re =
rhoQD/d2mu, a ratio of inertial effects to viscous effects. Rapid injections,
high viscosity, and small inclination with respect to gravity promote meniscus
formation. These results can be used to refine the guidelines for administration
of surfactant replacement therapy.
PMID- 9655786
TI - Repetitive prenatal glucocorticoid therapy reduces oxidative stress in the lungs
of preterm lambs.
AB - Repetitive courses of maternal prenatal glucocorticoids are often used in high
risk pregnancies with threatening preterm labor to induce lung maturation, but
the effects on the cellular oxidant-antioxidant balance in the fetal lung have
not been evaluated. We investigated the effect of repetitive treatment with
glucocorticoids, beginning early in gestation, on oxidative stress in the preterm
ovine lung. Pregnant ewes were randomized to receive one, two, three, or four
doses of 0.5 mg/kg betamethasone or saline placebo at 7-day intervals on 104,
111, 118, and 124 days gestation (n = 11 for each group). All lambs were
delivered preterm at 125 days gestation, and lung tissue was assayed for
antioxidant enzymes, lipid hydroperoxides, and carbonyl proteins. Lung manganese
superoxide dismutase, catalase, and glutathione peroxidase activity increased
after 1 dose of betamethasone given at 104 days gestation, whereas copper-zinc
superoxide dismutase activity increased after 2 doses given at 104 and 111 days
gestation. The activity of all four antioxidant enzymes further increased with
additional doses and was maximal after four doses of betamethasone. Lung lipid
hydroperoxide levels and carbonyl protein content decreased stepwise after each
dose of betamethasone and were lowest after four doses. Repetitive prenatal
glucocorticoid therapy increases antioxidant enzyme activity and reduces
oxidative stress in the lungs of preterm lambs, and these effects begin early in
gestation and persist for 2-3 wk.
PMID- 9655787
TI - Lack of effect of spaceflight on bone mass and bone formation in group-housed
rats.
AB - As part of an experiment to study the role of corticosteroids in bone changes
during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were
placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs)
aboard the space shuttle Columbia (STS-78). Control rats were group housed in a
similar manner in ground-based AEMs or standard vivarium cages. Adrenal
hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed
a lack of significant changes in bone mass and bone formation in these animals.
Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis
were nearly the same in flight and ground-based rats. Normal levels of cancellous
bone mass and bone formation were also detected in the lumbar vertebrae and
femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation
rate was found to be identical in flight and ground-based rats. The results
indicate that, under conditions of group housing in AEMs, spaceflight has minimal
effects on bone mass and bone formation in rapidly growing rats. These findings
emphasize the need to investigate the importance of rat age, strain, and
especially housing conditions for studies of the skeletal effects of spaceflight.
PMID- 9655788
TI - Hysteresis of the nasal pressure-flow relationship during hyperpnea in normal
subjects.
AB - Hysteresis of the nasal airway pressure-flow relationship (PFR) is seen during
hyperpnea, with lower nasal resistance during increasing inspiratory flow than
during decreasing flow. We hypothesized that the nasal PFR hysteresis arose in
the nasal vestibule airway because of progressive collapse during the
inspiration. We measured the inspiratory transnasal and transvestibular PFR for
one nasal passage in five normal subjects breathing via a nasal mask during
voluntary hyperventilation, both with voluntary nostril flaring and without
flaring. The inspiratory hysteresis (IH) was quantified as the ratio of the areas
under the descending and ascending pressure-flow curves. Flaring reduced the
vestibular IH from 1.96 +/- 0.06 to 1.15 +/- 0.06 and the nasal IH from 2.05 +/-
0.13 to 1.28 +/- 0.06 (both P < 0.01). Our results demonstrate that hysteresis
arises in the compliant vestibule segment of the nasal airway, likely because of
progressive collapse of the nasal vestibule during inspiration. The findings
suggest that hysteresis is prevented by voluntary nostril flaring maintained
throughout inspiration.
PMID- 9655789
TI - Alae nasi activation decreases nasal resistance during hyperoxic hypercapnia.
AB - It has been proposed that decreases in nasal resistance (Rn) during hypercapnia
are entirely due to vasoconstriction in the nasal cavity. We hypothesized that
alae nasi (AN) muscle activity dilates the nasal vestibule and contributes to the
decrease in Rn during hypercapnia. Nine normal subjects were studied during
hyperoxic hypercapnia (HH). Rn and vestibular resistance (Rvest) for one nasal
passage were measured simultaneously with the AN electromyogram before and after
nasal decongestion. HH decreased Rvest from 1.6 +/- 0.6 to 0.8 +/- 0.9 cmH2O . l
1 . s (predecongestant) and from 1.3 +/- 0.8 to 0.6 +/- 0.7 cmH2O . l-1 . s
(postdecongestant; both P < 0. 01). Nasal decongestant decreased Rn but not
Rvest. Significant inverse linear relationships between Rvest and AN
electromyogram were demonstrated for all subjects. We conclude that in normal
subjects during HH 1) decreases in Rvest are predominantly due to increases in AN
activity; and 2) decreases in Rn are due to a combination of mucosal
vasoconstriction and AN activation.
PMID- 9655790
TI - Neuropeptide Y and Y1-receptor agonists increase blood flow through arteriovenous
anastomoses in rat tail.
AB - The purpose of this study was to characterize neuropeptide Y (NPY)-induced
vasodilation in the rat tail. Sterile surgical technique was used (with
pentobarbital sodium anesthesia) to equip rats with a jugular catheter and a
blind-ended thermocouple reentrant tube next to the carotid artery. Tail skin and
core temperature were measured with thermocouples during experiments. Tail skin
blood flow was monitored with a laser Doppler flowmeter, and tail total blood
flow and volume were measured with plethysmography. After baseline data were
collected, saline, NPY (16, 32, 64, and 128 microg/kg), [Leu31 Pro34]NPY (63.25
microg/kg), or NPY[13-36] (44.7 microg/kg) was administered intravenously. Tail
total blood flow, volume, and tail skin temperature increased, whereas tail skin
blood flow and core temperature decreased in response to both NPY- and the Y1
receptor agonist [Leu31 Pro34]NPY but not in response to saline or NPY[13-36].
Studies conducted with the use of color microspheres demonstrated that
arteriovenous anastomoses are involved in this NPY-induced vasodilation.
PMID- 9655791
TI - Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.
AB - Persons with type II diabetes mellitus (DM), even without cardiovascular
complications have a decreased maximal oxygen consumption (VO2 max) and
submaximal oxygen consumption (VO2) during graded exercise compared with healthy
controls. We evaluated the hypothesis that change in the rate of VO2 in response
to the onset of constant-load exercise (measured by VO2-uptake kinetics) was
slowed in persons with type II DM. Ten premenopausal women with uncomplicated
type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had
a VO2 max test. On two separate occasions, subjects performed 7-min bouts of
constant-load bicycle exercise at workloads below and above the lactate threshold
to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of
heart rate rise). VO2 max was reduced in subjects with type II DM compared with
both lean and overweight controls (P < 0.05). Subjects with type II DM had slower
VO2 and heart rate kinetics than did controls at constant workloads below the
lactate threshold. The data suggest a notable abnormality in the cardiopulmonary
response at the onset of exercise in people with type II DM. The findings may
reflect impaired cardiac responses to exercise, although an additional defect in
skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also
possible.
PMID- 9655792
TI - Thermal drive contributes to hyperventilation during exercise in sheep.
AB - The etiology of exercise hypocapnia is unknown. The contributions of exercise
intensity (ExInt), lactic acid, environmental temperature, rectal temperature
(Tre), and physical conditioning to the variance in arterial CO2 tension (PaCO2)
in the exercising sheep were quantified. We hypothesized that thermal drive
contributes to hyperventilation. Four unshorn sheep were exercised at
approximately 30, 50, and 70% of maximal O2 consumption for 30 min, or until
exhaustion, both before and after 5 wk of physical conditioning. In addition, two
of the sheep were shorn and exercised at each intensity in a cold (<15 degrees C)
environment. Tre and O2 consumption were measured continuously. Lactic acid and
PaCO2 were measured at 5- to 10-min intervals. Data were analyzed by multiple
regression on PaCO2. During exercise, Tre rose and PaCO2 fell, except at the
lowest ExInt in the cold environment. Tre explained 77% of the variance in PaCO2,
and ExInt explained 5%. All other variables were insignificant. We conclude that,
in sheep, thermal drive contributes to hyperventilation during exercise.
PMID- 9655793
TI - Red blood cells do not contribute to removal of K+ released from exhaustively
working forearm muscle.
AB - K+ released from exercising muscle via K+ channels needs to be removed from the
interstitium into the blood to maintain high muscle cell membrane potential and
allow normal muscle contractility. Uptake by red blood cells has been discussed
as one mechanism that would also serve to regulate red blood cell volume, which
was found to be constant despite increased plasma osmolality and K+ concentration
([K+pl]). We evaluated exercise-related changes in [K+pl], pH, osmolality, mean
cellular Hb concentration, cell water, and red blood cell K+ concentration during
exhaustive handgrip exercise. Unidirectional 86Rb+ (K+) uptake by red blood cells
was measured in media with elevated extracellular K+, osmolarity, and
catecholamines to simulate particularly those exercise-related changes in plasma
composition that are known to stimulate K+ uptake. During exercise [K+pl]
increased from 4.4 +/- 0.7 to 7.1 +/- 0.5 mmol/l plasma water and red blood cell
K+ concentration increased from 137.2 +/- 6.0 to 144.6 +/- 4.6 mmol/l cell water
(P = 0.05), but the intracellular K+-to-mean cellular Hb concentration ratio
did not change. 86Rb+ uptake by red blood cells was increased by approximately
20% on stimulation, caused by activation of the Na+-K+ pump and Na+-K+-2Cl-
cotransport. Results indicate the K+ content of red blood cells did not change as
cells passed the exhaustively exercising forearm muscle despite the elevated
[K+pl]. The tendency for an increase in intracellular K+ concentration was due to
a slight, although statistically not significant, decrease in red blood cell
volume. K+ uptake, although elevated, was too small to move significant amounts
of K+ into red blood cells. Our results suggest that red blood cells do not
contribute to the removal of K+ released from muscle and do not regulate their
volume by K+ uptake during exhaustive forearm exercise.
PMID- 9655794
TI - A theoretical study of surfactant and liquid delivery into the lung.
AB - A computational study is presented for the transport of liquids and insoluble
surfactant through the lung airways, delivered from a source at the distal end of
the trachea. Four distinct transport regimes are considered: 1) the instilled
bolus may create a liquid plug that occludes the large airways but is forced
peripherally during mechanical ventilation; 2) the bolus creates a deposited film
on the airway walls, either from the liquid plug transport or from direct
coating, that drains under the influence of gravity through the first few airway
generations; 3) in smaller airways, surfactant species form a surface layer that
spreads due to surface-tension gradients, i.e., Marangoni flows; and 4) the
surfactant finally reaches the alveolar compartment where it is cleared according
to first-order kinetics. The time required for a quasi-steady-state transport
process to evolve and for the subsequent delivery of the dose is predicted.
Following fairly rapid transients, on the order of seconds, steady-state
transport develops and is governed by the interaction of Marangoni flow and
alveolar kinetics. Total delivery time is approximately 24 h for a typical first
dose. Numerical solutions show that both transit and delivery times are strongly
influenced by the strength of the preexisting surfactant and the geometric
properties of the airway network. Delivery times for follow-up doses can increase
significantly as the level of preexisting surfactant rises.
PMID- 9655795
TI - Assessment of cutaneous blood flow by using topographical perfusion mapping
techniques.
AB - The ability of laser Doppler scanning to reproduce the spatial pattern of
cutaneous vascular conductance (CVC) in a 6.25-cm2 area of skin was evaluated at
supine rest (28 degrees C), during thermal stress (cold and heat), and during
baroreceptor unloading with -40-mmHg lower body negative pressure (LBNP). The
spatial pattern of resting CVC was similar on 3 different days, varying by 6 +/-
3%. During cold stress, 89 +/- 2% of the skin area showed a decrease in skin
blood flow (37 +/- 2%), whereas heat stress increased CVC in 94 +/- 5% of the
skin area. During LBNP, the pattern of CVC response was not uniform, and
frequency analysis indicated that 47 +/- 5% of the pixels showed a reduction in
CVC (>1 SE), 28 +/- 2% of the skin area were unaffected, and the remaining 26 +/-
5% of the pixels showed some increase in CVC. These data indicate the ability of
topographical perfusion mapping to provide quantitative and reproducible
information about the spatial distribution of CVC. In addition, the site-to-site
variability in reflex control of skin blood flow during LBNP is intriguing and
requires more rigorous evaluation.
PMID- 9655796
TI - Differential inspiratory timing is genetically linked to mouse chromosome 3.
AB - Genetic control of differential inspiratory timing (TI) at baseline has been
previously demonstrated among inbred mouse strains. The inheritance pattern for
TI between C3H/HeJ (C3; 188 +/- 3 ms) and C57BL/6J (B6; 111 +/- 2 ms) progenitors
was consistent with a two-gene model. By using the strain distribution pattern
for recombinant inbred strains derived from C3 and B6 progenitors, 100%
concordance was established between TI phenotypes and DNA markers on mouse
chromosome 3. This genotype-phenotype hypothesis was tested by typing 52 B6C3F2
(F2) progeny by using simple sequence repeat DNA markers (n = 21) polymorphic
between C3 and B6 strains on mouse chromosome 3. Linkage analysis compared marker
genotypes to baseline ventilatory phenotypes by computing log-likelihood values.
A putative quantitative trait locus located in proximity to D3Mit119 was
significantly associated with baseline TI phenotypes. At the peak (log-likelihood
= 3.3), the putative quantitative trait locus determined 25% of the phenotypic
variance in TI among F2 progeny. In conclusion, this genetic model of ventilatory
characteristics demonstrated an important linkage between differential baseline
TI and a candidate genomic region on mouse chromosome 3.
PMID- 9655797
TI - Effect of sleep/wake state on arterial blood pressure in genetically identical
mice.
AB - Genetic determinants may contribute to the large variability in arterial blood
pressure responses to changes in sleep/wake state in humans. In this study, we
developed techniques to examine the relationship between sleep/wake state and
mean arterial pressure (MAP) in unrestrained, genetically identical mice
(C57BL/6J; n = 9). The left common carotid artery was catheterized, and arterial
blood gases were analyzed 24-48 h postsurgery to verify normal respiratory and
metabolic function. The animals were then allowed to cycle naturally through
sleep/wake states over a 3- to 4-h period while continuous polysomnography and
arterial pressure measurements were made. The MAP decreased from quiet
wakefulness to non-rapid-eye-movement sleep (9.8 +/- 1.3 mmHg; P < 0.001) and
further decreased from non-rapid-eye-movement to rapid-eye-movement sleep (9.7 +/
1.8 mmHg; P < 0.001). We conclude that the inbred strain of C57BL/6J mice
exhibits significant and consistent changes in MAP related to sleep/wake state.
Future studies can compare responses in this strain of mice with those in other
inbred or transgenic mice to determine whether specific genes regulate arterial
blood pressure responses to sleep/wake state.
PMID- 9655798
TI - NF-kappaB induction during in vivo hypoxia in dorsocaudal brain stem of rat:
effect of MK-801 and L-NAME.
AB - In the nucleus of the solitary tract, NMDA receptors are critical for the hypoxic
ventilatory response while neuronal nitric oxide synthase (NOS) modulates the
late component of this response. Nuclear factor (NF)-kappaB is a ubiquitous
transcription factor that increases the expression of multiple stress-activated
genes. We sought to examine temporal changes in expression of NF-kappaB within
the dorsocaudal brain stem of conscious rats after exposures to 10% O2. Time
dependent increases in NF-kappaB occurred with hypoxia and peaked at 60 min.
Pretreatment with the N-methyl-D-aspartate (NMDA)-receptor channel antagonist
dizocilpine maleate (MK-801) markedly attenuated NF-kappaB complexes during
hypoxia. In contrast, after NOS inhibition with NG-nitro-L-arginine methyl ester
(L-NAME), although NF-kappaB was diminished in normoxia, increased NF-kappaB
expression still occurred with hypoxia. Increased phosphorylation of the NF
kappaB regulatory unit [inhibitory (I)kappaB] was detected by immunoblotting and
also peaked at 60 min. Phosphorylation of Ikappa-B during hypoxia was attenuated
by MK-801 but not by L-NAME. Thus NMDA-receptor activation in the dorsocaudal
brain stem during hypoxia elicits in NF-kappaB activity marked enhancements that
are unaffected after NOS blockade.
PMID- 9655799
TI - Gli2 is required for induction of floor plate and adjacent cells, but not most
ventral neurons in the mouse central nervous system.
AB - Induction of the floor plate at the ventral midline of the neural tube is one of
the earliest events in the establishment of dorsoventral (d/v) polarity in the
vertebrate central nervous system (CNS). The secreted molecule, Sonic hedgehog,
has been shown to be both necessary and sufficient for this induction. In
vertebrates, several downstream components of this signalling pathway have been
identified, including members of the Gli transcription factor family. In this
study, we have examined d/v patterning of the CNS in Gli2 mouse mutants. We have
found that the floor plate throughout the midbrain, hindbrain and spinal cord
does not form in Gli2 homozygotes. Despite this, motoneurons and ventral
interneurons form in their normal d/v positions at 9.5 to 12.5 days postcoitum
(dpc). However, cells that are generated in the region flanking the floor plate,
including dopaminergic and serotonergic neurons, were greatly reduced in number
or absent in Gli2 homozygous embryos. These results suggest that early signals
derived from the notochord can be sufficient for establishing the basic d/v
domains of cell differentiation in the ventral spinal cord and hindbrain.
Interestingly, the notochord in Gli2 mutants does not regress ventrally after
10.5 dpc, as in normal embryos. Finally, the spinal cord of Gli1/Gli2 zinc-finger
deletion double homozygous mutants appeared similar to Gli2 homozygotes,
indicating that neither gene is required downstream of Shh for the early
development of ventral cell fates outside the ventral midline.
PMID- 9655800
TI - engrailed and polyhomeotic interactions are required to maintain the A/P boundary
of the Drosophila developing wing.
AB - Engrailed is a nuclear regulatory protein with essential roles in embryonic
segmentation and wing morphogenesis. One of its regulatory targets in embryos was
shown to be the Polycomb group gene, polyhomeotic. We show here that
transheterozygous adult flies, mutant for both engrailed and polyhomeotic, show a
gap in the fourth vein. In the corresponding larval imaginal discs, a
polyhomeotic-lacZ enhancer trap is not normally activated in anterior cells
adjacent to the anterior-posterior boundary. This intermediary region corresponds
to the domain of low engrailed expression that appears in the anterior
compartment, during L3. Several arguments show that engrailed is responsible for
the induction of polyhomeotic in these cells. The role of polyhomeotic in this
intermediary region is apparently to maintain the repression of hedgehog in the
anterior cells abutting the anterior-posterior boundary, since these cells
ectopically express hedgehog when polyhomeotic is not activated. This leads to
ectopic expressions first of patched, then of cubitus interruptus and
decapentaplegic in the posterior compartment, except for the dorsoventral border
cells that are not affected. Thus posterior cells express a new set of genes that
are normally characteristic of anterior cells, suggesting a change in the cell
identity. Altogether, our data indicate that engrailed and polyhomeotic
interactions are required to maintain the anterior-posterior boundary and the
posterior cell fate, just prior to the evagination of the wing.
PMID- 9655801
TI - Morphogenesis of the Drosophila fusome and its implications for oocyte
specification.
AB - The Drosophila oocyte develops within a cyst of 16 germline cells interconnected
by ring canals. Polarized, microtubule-based transport of unknown determinants is
required for oocyte formation, but whether polarity is established during or
after cyst formation is not clear. We have analyzed how polarity develops in stem
cells and dividing cysts by following the growth of the fusome, a vesiculated
cytoplasmic organelle. Our studies show that the fusome grows by a regular,
polarized process throughout the stem cell and cyst cell cycles. Each
polarization cycle begins in mitosis, when the fusome segregates to a single
daughter cell of each pair. Following mitosis, a 'plug' of fusomal material forms
in each nascent ring canal and gradually fuses with the pre-existing fusome. In
stem cells, the ring canal is transient and closes down after the fusome is
partitioned through it. In dividing cysts, as the fusome plugs move toward the
pre-existing fusome, their associated ring canals also move, changing the
geometry of the cyst. At the end of each cycle of cyst growth, the fusome remains
asymmetrically distributed within the cyst; one of the two cells with four ring
canals retains a bigger piece of fusome than any other cell, including the other
cell with four ring canals. Based on these observations, we argue that the oocyte
is specified at the first cyst division.
PMID- 9655802
TI - Epithelial-mesenchymal signaling during the regionalization of the chick gut.
AB - The development of the vertebrate gut requires signaling between the endoderm and
mesoderm for establishing its normal anteroposterior (AP) axis and for tissue
specific differentiation. Factors implicated in positional specification of the
AP regions of the gut include endodermally expressed Sonic hedgehog (Shh),
mesodermally expressed Bmp4 and members of the Hox gene family. We have
investigated the roles of these factors during AP regional specification of the
chick embryonic gut. Early in gut development, the endoderm sends inductive
signals to the mesoderm. Shh has been implicated as one of these signals. We find
a differential response to exposure of the inductive influence of Shh along the
AP axis of the gut. Virally mediated misexpression of Shh results in ectopic
upregulation of its receptor Ptc and a cellular proliferation throughout the gut
mesoderm. Although ectopic Shh can induce Bmp4 in the mesoderm of the midgut and
hindgut, Bmp4 is not induced in the stomach region of the foregut. The stomach
region has a thicker layer of mesoderm than the rest of the gut suggesting that
the normal function of Bmp4 could be to limit mesodermal growth in the non
stomach regions of the gut. Ectopic Bmp4 expression in the stomach results in a
reduction of the mesodermal component consistent with this hypothesis. In
addition to the regional restriction on Bmp4 induction, Shh can only induce Hoxd
13 in the mesoderm of the hindgut. These findings suggest that a prepattern
exists in the primitive gut mesoderm prior to expression of Shh in the endoderm.
The gut mesoderm is subsequently responsible for inducing region-specific
differentiation of its overlying endoderm. We tested the role of Hoxd-13,
normally restricted in its mesodermal expression to the most posterior region of
the hindgut (cloaca), in controlling adjacent endodermal differentiation. When
virally mediated Hoxd-13 is misexpressed in the primitive midgut mesoderm, there
is a transformation of the endoderm to the morphology and mucin content of the
hindgut. Thus, the positionally restricted expression of a Hox gene in the gut
mesoderm influences the inductive signaling that leads to regionally specific
differentiation of gut endoderm.
PMID- 9655803
TI - The Shh signalling pathway in tooth development: defects in Gli2 and Gli3
mutants.
AB - The expression of genes involved in the Sonic Hedgehog signalling pathway,
including Shh, Ptc, Smo, Gli1, Gli2 and Gli3, were found to be expressed in
temporal and spatial patterns during early murine tooth development, suggestive
of a role in early tooth germ initiation and subsequent epithelial-mesenchymal
interactions. Of these Ptc, Smo, Gli1, Gli2 and Gli3 were expressed in epithelium
and mesenchyme whereas Shh was only detected in epithelium. This suggests that
Shh is involved in both lateral (epithelial-mesenchymal) and planar (epithelial
epithelial) signalling in early tooth development. Ectopic application of Shh
protein to mandibular mesenchyme induced the expression of Ptc and Gli1. Addition
of exogenous Shh protein directly into early tooth germs and adjacent to tooth
germs, resulted in abnormal epithelial invagination, indicative of a role for Shh
in epithelial cell proliferation. In order to assess the possible role of this
pathway, tooth development in Gli2 and Gli3 mutant embryos was investigated. Gli2
mutants were found to have abnormal development of maxillary incisors, probably
resulting from a mild holoprosencephaly, whereas Gli3 mutants had no major tooth
abnormalities. Gli2/Gli3 double homozygous mutants did not develop any normal
teeth and did not survive beyond embryonic day 14.5; however, Gli2(-/-); Gli3(+/
) did survive until birth and had small molars and mandibular incisors whereas
maxillary incisor development was arrested as a rudimentary epithelial
thickening. These results show an essential role for Shh signalling in tooth
development that involves functional redundancy of downstream Gli genes.
PMID- 9655804
TI - Leafbladeless1 is required for dorsoventrality of lateral organs in maize.
AB - The maize leafbladeless1 (lbl1) mutant displays a variety of leaf and plant
phenotypes. The most extreme manifestation in the leaf is the formation of
radially symmetric, abaxialized leaves due to a complete loss of adaxial cell
types. Less severe phenotypes, resulting from a partial loss of adaxial cell
identity, include the formation of ectopic laminae at the boundary between
abaxialized, mutant sectors on the adaxial leaf surface and the bifurcation of
leaves. Ectopic laminae and bifurcations arise early in leaf development and
result in an altered patterning of the leaf along the proximodistal axis, or in
complete duplication of the developing organ. Leaf-like lateral organs of the
inflorescences and flowers show similar phenotypes. These observations suggest
that Lbl1 is required for the specification of adaxial cell identity within
leaves and leaf-like lateral organs. Lbl1 is also required for the lateral
propagation of leaf founder cell recruitment, and plays a direct or indirect role
in the downregulation of the homeobox gene, knotted1, during leaf development.
Our results suggest that adaxial/abaxial asymmetry of lateral organs is specified
in the shoot apical meristem, and that formation of this axis is essential for
marginal, lateral growth and for the specification of points of proximodistal
growth. Parallels between early patterning events during lateral organ
development in plants and animals are discussed.
PMID- 9655805
TI - Differential regulation of T-box and homeobox transcription factors suggests
roles in controlling chick limb-type identity.
AB - The wing and the leg of the chick, although homologous structures, have
characteristic patterns of skeletal elements, muscles, tendons, featherbuds and
scales. Despite recent advances in understanding the common genetic pathways
patterning the wing and leg, the molecular nature of the specification of limb
type identity has remained elusive. Embryological experiments have indicated the
existence of limb-specific territories in the flank. In the newt, deviation of
nerves from the limb into the flank can induce ectopic limbs to form from this
tissue. In the chick, Fibroblast growth factor (FGF)-soaked beads applied to the
flank can induce ectopic formation of limbs from the surrounding tissue. In both
cases, the type of limb that forms, either a wing/forelimb or leg/hindlimb, is
dependent upon the location to which the limb-inducing signal is applied. We have
isolated and characterised three candidate genes for controlling limb identity in
the chick. Two T-box transcription factors, cTbx4 and cTbx5, are expressed in a
restricted manner in the leg bud and wing buds, respectively. cPtx1, a member of
the Otx-related subclass of paired-type homeodomain proteins, is expressed
exclusively in the leg bud. Using FGF to induce ectopic limb buds of wing, leg
and intermediate identity, we show that early expression of cTbx5, cTbx4 and
cPtx1 in the induced limb buds correlates with later wing- or leg-type identity
of ectopic limbs. We observe a general correlation between the location of an
ectopic outgrowth induced by FGF and the identity of the resulting limb but,
significantly, we report that there is no definitive rostral-caudal level that
divides the ectopic wing and leg territories.
PMID- 9655806
TI - Patterning of the follicle cell epithelium along the anterior-posterior axis
during Drosophila oogenesis.
AB - Gurken signals from the oocyte to the adjacent follicle cells twice during
Drosophila oogenesis; first to induce posterior fate, thereby polarising the
anterior-posterior axis of the future embryo and then to induce dorsal fate and
polarise the dorsal-ventral axis. Here we show that Gurken induces two different
follicle cell fates because the follicle cells at the termini of the egg chamber
differ in their competence to respond to Gurken from the main-body follicle cells
in between. By removing the putative Gurken receptor, Egfr, in clones of cells,
we show that Gurken signals directly to induce posterior fate in about 200 cells,
defining a terminal competence domain that extends 10-11 cell diameters from the
pole. Furthermore, small clones of Egfr mutant cells at the posterior interpret
their position with respect to the pole and differentiate as the appropriate
anterior cell type. Thus, the two terminal follicle cell populations contain a
symmetric prepattern that is independent of Gurken signalling. These results
suggest a three-step model for the anterior-posterior patterning of the
follicular epithelium that subdivides this axis into at least five distinct cell
types. Finally, we show that Notch plays a role in both the specification and
patterning of the terminal follicle cells, providing a possible explanation for
the defect in anterior-posterior axis formation caused by Notch and Delta
mutants.
PMID- 9655807
TI - Basal ganglia precursors found in aggregates following embryonic transplantation
adopt a striatal phenotype in heterotopic locations.
AB - Transplantation of immature CNS-derived cells into the developing brain is a
powerful approach to investigate the factors that regulate neuronal position and
phenotype. CNS progenitor cells dissociated from the embryonic striatum and
implanted into the brain of embryos of the same species generate cells that
reaggregate to form easily recognizable structures that we previously called
clusters and cells that disperse and integrate as single cells into the host
brain. We sought to determine if the neurons in the clusters differentiate
according to their final location or acquire a striatal phenotype in heterotopic
positions. We transplanted dissociated cells from the E14 rat medial and lateral
ganglionic eminences, either combined or in isolation, into the E16 embryonic rat
brain. At all time points, we found clusters of BrdU- and DiI-labelled donor
cells located in the forebrain and hindbrain, without any apparent preference for
striatum. Immunocytochemical analyses revealed that cells in the clusters
expressed DARPP-32 and ARPP-21, two antigens typically co-expressed in striatal
medium-sized spiny neurons. In agreement with observations previously noted by
several groups, isolated cells integrated into heterologous host areas do not
express basal ganglia phenotypes. These data imply that immature striatal
neuronal progenitors exert a community effect on each other that is permissive
and/or instructive for development of a striatal phenotype in heterotopic
locations.
PMID- 9655808
TI - The rough sheath2 gene negatively regulates homeobox gene expression during maize
leaf development.
AB - Leaves of higher plants are produced in a sequential manner through the
differentiation of cells that are derived from the shoot apical meristem. Current
evidence suggests that this transition from meristematic to leaf cell fate
requires the down-regulation of knotted1-like homeobox (knox) gene expression. If
knox gene expression is not repressed, overall leaf shape and cellular
differentiation within the leaf are perturbed. In order to identify genes that
are required for the aquisition of leaf cell fates, we have genetically screened
for recessive mutations that confer phenotypes similar to dominant mutations
(e.g. Knotted1 and Rough sheath1) that result in the ectopic expression of class
I knox genes. Independently derived mutations at the rough sheath2 (rs2) locus
condition a range of pleiotropic leaf, node and internode phenotypes that are
sensitive to genetic background and environment. Phenotypes include dwarfism,
leaf twisting, disorganized differentiation of the blade-sheath boundary,
aberrant vascular patterning and the generation of semi-bladeless leaves. knox
genes are initially repressed in rs2 mutants as leaf founder cells are recruited
in the meristem. However, this repression is often incomplete and is not
maintained as the leaf progresses through developement. Expression studies
indicate that three knox genes are ectopically or over-expressed in developing
primordia and in mature leaves. We therefore propose that the rs2 gene product
acts to repress knox gene expression (either directly or indirectly) and that rs2
gene action is essential for the elaboration of normal leaf morphology.
PMID- 9655809
TI - Opl: a zinc finger protein that regulates neural determination and patterning in
Xenopus.
AB - In order to study the mechanism of neural patterning in Xenopus, we used
subtractive cloning to isolate genes activated early during this process. One
gene isolated was opl, (odd-paired-like) that resembles the Drosophila pair-rule
gene odd-paired and encodes a zinc finger protein that is a member of the Zic
gene family. At the onset of gastrulation, opl is expressed throughout the
presumptive neural plate, indicating that neural determination has begun at this
stage while, by neurula, opl expression is restricted to the dorsal neural tube
and neural crest. opl encodes a transcriptional activator, with a carboxy
terminal regulatory domain, which when removed increases opl activity. opl both
sensitizes animal cap ectoderm to the neural inducer noggin and alters the
spectrum of genes induced by noggin, allowing activation of the midbrain marker
engrailed. Consistent with the later dorsal neural expression of opl, the
activated form of opl is able to induce neural crest and dorsal neural tube
markers both in animal caps and whole embryos. In ventral ectoderm, opl induces
formation of loose cell aggregates that may indicate neural crest precursor
cells. Aggregates do not express an epidermal marker, indicating that opl
suppresses ventral fates. Together, these data suggest that opl may mediate
neural competence and may be involved in activation of midbrain, dorsal neural
and neural crest fates.
PMID- 9655810
TI - Src64 is required for ovarian ring canal morphogenesis during Drosophila
oogenesis.
AB - The Src family of protein tyrosine kinases have been implicated as important
regulators of cellular proliferation, differentiation and function. In order to
understand further the role of Src family kinases, we have generated loss-of
function mutations in Src64, one of two Src family kinases known in Drosophila
melanogaster. Animals with reduced Src64 function develop normally and are fully
viable. However, Src64 female flies have reduced fertility, which is associated
with the incomplete transfer of cytoplasm from nurse cells to the developing
oocyte. Analysis of Src64 egg chambers showed defects in the ring canals that
interconnect the oocyte and its 15 associated nurse cells. Src64 ring canals fail
to accumulate the high levels of tyrosine phosphorylation that are normally
present. Despite the reduced tyrosine phosphorylation, known ring canal
components such as filamentous actin, a ring canal-specific product of the hu-li
tai shao gene, and the kelch protein localize properly. However, Src64 ring
canals are reduced in size and frequently degenerate. These results indicate that
Src64 is required for the proper growth and stability of the ovarian ring canals.
PMID- 9655811
TI - A subset of notch functions during Drosophila eye development require Su(H) and
the E(spl) gene complex.
AB - The Notch signalling pathway is involved in many processes where cell fate is
decided. Previous work showed that Notch is required at successive steps during
R8 specification in the Drosophila eye. Initially, Notch enhances atonal
expression and promotes atonal function. After atonal autoregulation has been
established, Notch signalling represses atonal expression during lateral
specification. In this paper we investigate which known components of the Notch
pathway are involved in each signalling process. Using clonal analysis we show
that a ligand of Notch, Delta, is required along with Notch for both proneural
enhancement and lateral specification, while the downstream components Suppressor
of-Hairless and Enhancer-of-Split are involved only in lateral specification. Our
data point to a distinct signal transduction pathway during proneural enhancement
by Notch. Using misexpression experiments we also show that particular Enhancer
of-split bHLH genes can differ greatly in their contribution to lateral
specification.
PMID- 9655812
TI - A role for glutamate and its receptors in the regulation of oligodendrocyte
development in cerebellar tissue slices.
AB - We tested the hypothesis that the neurotransmitter glutamate would influence
glial proliferation and differentiation in a cytoarchitecturally intact system.
Postnatal day 6 cerebellar slices were maintained in organotypic culture and
treated with glutamate receptor agonists or antagonists. After dissociation,
cells were stained with antibodies for different oligodendrocyte developmentally
regulated antigens. Treatment of the slices with the glutamate receptor agonists
kainate or alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
significantly decreased the percentage of LB1(+), NG2(+) and O4(+) cells, and
their bromodeoxyuridine labeling index. The non-N-methyl-D-aspartate glutamate
receptor antagonist 6,7-dinitroquinoxaline-2,3-dione increased the percentage and
bromodeoxyuridine labeling of LB1(+), NG2(+) and O4(+) cells. In intact slices,
RNA levels of the oligodendrocyte gene for 2',3'-cyclic nucleotide 3'
phosphodiesterase were decreased by kainate and alpha-amino-3-hydroxy-5-methyl-4
isoxazolepropionic acid, and increased by 6,7-dinitroquinoxaline-2,3-dione. The
percentage of astrocytes was not modified by kainate, alpha -amino-3-hydroxy-5
methyl-4-isoxazolepropionic acid or 6, 7-dinitroquinoxaline-2,3-dione. Treatment
with the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoic
acid did not alter the percentage of O4(+) cells, nor their proliferation.
Incubation with the gamma-aminobutyric acid receptor antagonist bicuculline did
not modify the percentage of LB1(+), A2B5(+) and O4(+) cells. In purified
cerebellar oligodendrocyte progenitor cells, glutamate receptor agonists blocked
K+ currents, and inhibited cell proliferation and lineage progression. The K+
channel blocker tetraethylammonium also inhibited oligodendrocyte progenitor cell
proliferation. These findings indicate that in rat cerebellar tissue slices: (i)
glutamate specifically modulates oligodendrocyte but not astrocyte development
through selective activation of alpha -amino-3-hydroxy-5-methyl-4
isoxazolepropionic acid receptors, and (ii) cell depolarization and blockage of
voltage-dependent K+ channels is likely to be the triggering mechanism.
PMID- 9655813
TI - Transgene expression of steel factor in the basal layer of epidermis promotes
survival, proliferation, differentiation and migration of melanocyte precursors.
AB - Mutations at the murine dominant white spotting (KitW) and steel (MgfSl) loci,
encoding c-Kit receptor kinase and its ligand respectively, exert developmental
defects on hematopoietic cells, melanocytes, germ cells and interstitial cells of
Cajal. The expression patterns of steel factor (SLF) observed in the skin and
gonads suggest that SLF mediates a migratory or a chemotactic signal for c-Kit
expressing stem cells (melanocyte precursors and primordial germ cells). By
targeting expression of SLF to epidermal keratinocytes in mice, we observed
extended distribution of melanocytes in a number of sites including oral
epithelium and footpads where neither melanocytes nor their precursors are
normally detected. In addition, enlarged pigmented spots of KitW and other
spotting mutant mice were observed in the presence of the SLF transgene. These
results provide direct evidence that SLF stimulates migration of melanocytes in
vivo. We also present data suggesting that SLF does not simply support survival
and proliferation of melanocytes but also promotes differentiation of these
cells. Unexpectedly, melanocyte stem cells independent of the c-Kit signal were
maintained in the skin of the SLF transgenic mice. After the elimination of c-Kit
dependent melanoblasts by function-blocking anti-c-Kit antibody, these stem cells
continued to proliferate and differentiate into mature melanocytes. These
melanoblasts are able to migrate to cover most of the epidermis after several
months. The SLF transgenic mice described in this report will be useful in the
study of melanocyte biology.
PMID- 9655814
TI - Localized changes in apoplastic and cytoplasmic pH are associated with root hair
development in Arabidopsis thaliana.
AB - Morphogenesis in plants is characterized by highly regulated cell enlargement.
However, the mechanisms controlling and localizing regions of growth remain
essentially unknown. Root hair formation involves the induction of a localized
cell expansion in the lateral wall of a root epidermal cell. This expanded region
then enters a second phase of localized growth called tip growth. Root hair
formation therefore provides a model in which to study the cellular events
involved in regulating localized growth in plants. Confocal ratio imaging of the
pH of the cell wall revealed an acidification at the root hair initiation site.
This acidification was present from the first morphological indications of
localized growth, but not before, and was maintained to the point where the
process of root hair initiation ceased and tip growth began. Preventing the wall
acidification with pH buffers arrested the initiation process but growth resumed
when the wall was returned to an acidic pH. Cytoplasmic pH was found to be
elevated from approximately 7.3 to 7. 7 at the initiation site, and this
elevation coincided with the acidification of the wall. Preventing the localized
increase in cytoplasmic pH with 10 mM butyrate however did not inhibit either the
wall acidification or the initiation process. In contrast, there was no
detectable gradient in pH associated with the apex of tip growing root hairs, but
both elevated apoplastic pH and butyrate treatment irreversibly inhibited the tip
growth process. Thus the processes of tip growth and initiation of root hairs
show differences in their pH requirements. These results highlight the role of
localized control of apoplastic pH in the control of cell architecture and
morphogenesis in plants.
PMID- 9655815
TI - Leaf polarity and meristem formation in Arabidopsis.
AB - Shoot apical meristems (SAMs) of seed plants are small groups of pluripotent
cells responsible for making leaves, stems and flowers. While the primary SAM
forms during embryogenesis, new SAMs, called axillary SAMs, develop later on the
body of the plant and give rise to branches. In Arabidopsis plants, axillary SAMs
develop in close association with the adaxial leaf base at the junction of the
leaf and stem (the leaf axil). We describe the phenotype caused by the
Arabidopsis phabulosa-1d (phb-1d) mutation. phb-1d is a dominant mutation that
causes altered leaf polarity such that adaxial characters develop in place of
abaxial leaf characters. The adaxialized leaves fail to develop leaf blades. This
supports a recently proposed model in which the juxtaposition of ad- and abaxial
cell fates is required for blade outgrowth. In addition to the alteration in leaf
polarity, phb-1d mutants develop ectopic SAMs on the undersides of their leaves.
Also, the phb-1d mutation weakly suppresses the shoot meristemless (stm) mutant
phenotype. These observations indicate an important role for adaxial cell fate in
promoting the development of axiallary SAMs and suggest a cyclical model for
shoot development: SAMs make leaves which in turn are responsible for generating
new SAMs.
PMID- 9655816
TI - shaven and sparkling are mutations in separate enhancers of the Drosophila Pax2
homolog.
AB - We have previously shown that the sparkling gene, which like mammalian Pax2 plays
an important role in eye development, is encoded by the Drosophila homolog of
Pax2. Here we demonstrate that D-Pax2 also encodes the shaven function, which is
crucial during bristle development. Both sv and spa alleles, previously thought
to represent different genes, are mutations in two widely separated enhancers of
D-Pax2. The sv function of D-Pax2 acts in at least two distinct steps of
mechanosensory bristle development: the specification of the alternative fate of
shaft as opposed to socket cell, and later the differentiation of the shaft cell.
PMID- 9655817
TI - Interactions among Delta, Serrate and Fringe modulate Notch activity during
Drosophila wing development.
AB - The Notch signalling pathway plays an important role during the development of
the wing primordium, especially of the wing blade and margin. In these processes,
the activity of Notch is controlled by the activity of the dorsal specific
nuclear protein Apterous, which regulates the expression of the Notch ligand,
Serrate, and the Fringe signalling molecule. The other Notch ligand, Delta, also
plays a role in the development and patterning of the wing. It has been proposed
that Fringe modulates the ability of Serrate and Delta to signal through Notch
and thereby restricts Notch signalling to the dorsoventral boundary of the
developing wing blade. Here we report the results of experiments aimed at
establishing the relationships between Fringe, Serrate and Delta during wing
development. We find that Serrate is not required for the initiation of wing
development but rather for the expansion and early patterning of the wing
primordium. We provide evidence that, at the onset of wing development, Delta is
under the control of apterous and might be the Notch ligand in this process. In
addition, we find that Fringe function requires Su(H). Our results suggest that
Notch signalling during wing development relies on careful balances between
positive and dominant negative interactions between Notch ligands, some of which
are mediated by Fringe.
PMID- 9655818
TI - Neural crest emigration from the neural tube depends on regulated cadherin
expression.
AB - During the emergence of neural crest cells from the neural tube, the expression
of cadherins dynamically changes. In the chicken embryo, the early neural tube
expresses two cadherins, N-cadherin and cadherin-6B (cad6B), in the dorsal-most
region where neural crest cells are generated. The expression of these two
cadherins is, however, downregulated in the neural crest cells migrating from the
neural tube; they instead begin expressing cadherin-7 (cad7). As an attempt to
investigate the role of these changes in cadherin expression, we overexpressed
various cadherin constructs, including N-cadherin, cad7, and a dominant negative
N-cadherin (cN390 ), in neural crest-generating cells. This was achieved by
injecting adenoviral expression vectors encoding these molecules into the lumen
of the closing neural tube of chicken embryos at stage 14. In neural tubes
injected with the viruses, efficient infection was observed at the neural crest
forming area, resulting in the ectopic cadherin expression also in migrating
neural crest cells. Notably, the distribution of neural crest cells with the
ectopic cadherins changed depending on which constructs were expressed. Many
crest cells failed to escape from the neural tube when N-cadherin or cad7 was
overexpressed. Moreover, none of the cells with these ectopic cadherins migrated
along the dorsolateral (melanocyte) pathway. When these samples were stained for
Mitf, an early melanocyte marker, positive cells were found accumulated within
the neural tube, suggesting that the failure of their migration was not due to
differentiation defects. In contrast to these phenomena, cells expressing non
functional cadherins exhibited a normal migration pattern. Thus, the
overexpression of a neuroepithelial cadherin (N-cadherin) and a crest cadherin
(cad7) resulted in the same blocking effect on neural crest segregation from
neuroepithelial cells, especially for melanocyte precursors. These findings
suggest that the regulation of cadherin expression or its activity at the neural
crest-forming area plays a critical role in neural crest emigration from the
neural tube.
PMID- 9655819
TI - Overexpression of the forebrain-specific homeobox gene six3 induces rostral
forebrain enlargement in zebrafish.
AB - The Drosophila homeobox gene sine oculis is expressed in the rostral region of
the embryo in early development and is essential for eye and brain formation. Its
murine homolog, Six3, is expressed in the anterior neural plate and eye anlage,
and may have crucial functions in eye and brain development. In this study, we
describe the cloning and expression of zebrafish six3, the apparent ortholog of
the mouse Six3 gene. Zebrafish six3 transcripts are first seen in hypoblast cells
in early gastrula embryos and are found in the anterior axial mesendoderm through
gastrulation. six3 expression in the head ectoderm begins at late gastrula.
Throughout the segmentation period, six3 is expressed in the rostral region of
the prospective forebrain. Overexpression of six3 in zebrafish embryos induced
enlargement of the rostral forebrain, enhanced expression of pax2 in the optic
stalk and led to a general disorganization of the brain. Disruption of either the
Six domain or the homeodomain abolish these effects, implying that these domains
are essential for six3 gene function. Our results suggest that the vertebrate
Six3 genes are involved in the formation of the rostral forebrain.
PMID- 9655820
TI - Sonic hedgehog is not required for the induction of medial floor plate cells in
the zebrafish.
AB - Sonic hedgehog (Shh) is a secreted protein that is involved in the organization
and patterning of several tissues in vertebrates. We show that the zebrafish
sonic-you (syu) gene, a member of a group of five genes required for somite
patterning, is encoding Shh. Embryos mutant for a deletion of syu display defects
in patterning of the somites, the lateral floor plate cells, the pectoral fins,
the axons of motorneurons and the retinal ganglion cells. In contrast to mouse
embryos lacking Shh activity, syu mutant embryos do form medial floor plate cells
and motorneurons. Since ectopic overexpression of shh in zebrafish embryos does
not induce ectopic medial floor plate cells, we conclude that shh is neither
required nor sufficient to induce this cell type in the zebrafish.
PMID- 9655821
TI - Cytoplasmic polyadenylation of Toll mRNA is required for dorsal-ventral
patterning in Drosophila embryogenesis.
AB - Toll encodes a receptor that is critical for dorsal-ventral patterning in the
early Drosophila embryo. Previous data have suggested that the accumulation of
Toll protein in the embryo temporally correlates with elongation of the poly (A)
tail of the message. Here, we demonstrate that Toll mRNA is translationally
activated by regulated cytoplasmic polyadenylation. We also identify a 192
nucleotide regulatory element in the Toll 3' UTR that is necessary for robust
translational activation of Toll mRNA and also regulates polyadenylation. UV
crosslinking analyses suggest that two proteins bind specifically to the 192
nucleotide element. One or both of these proteins may be factors that are
required for translational regulation or cytoplasmic polyadenylation. These
studies demonstrate that regulated polyadenylation plays a critical role in the
Drosophila dorsal-ventral patterning system.
PMID- 9655823
TI - Conformational changes on substrate binding to methylmalonyl CoA mutase and new
insights into the free radical mechanism.
AB - BACKGROUND: Methylmalonyl CoA mutase catalyses the interconversion of succinyl
CoA and methylmalonyl CoA via a free radical mechanism. The enzyme belongs to a
family of enzymes that catalyse intramolecular rearrangement reactions in which a
group and a hydrogen atom on adjacent carbons are exchanged. These enzymes use
the cofactor adenosylcobalamin (coenzyme B12) which breaks to form an adenosyl
radical, thus initiating the reaction. Determination of the structure of
substrate-free methylmalonyl CoA mutase was initiated to provide further insight
into the mechanism of radical formation. RESULTS: We report here two structures
of methylmalonyl CoA mutase from Propionibacterium shermanii. The first structure
is of the enzyme in a nonproductive complex with CoA at 2.5 A resolution. This
structure serves as a model for the substrate-free conformation of the enzyme, as
it is very similar to the second much poorer 2.7 A resolution structure derived
from a truly substrate-free crystal. The true substrate-free structure also shows
the adenosyl group bound to the cobalt atom. Comparison of this structure with
that of the previously reported complex of the enzyme with a substrate analogue
shows that major conformational changes occur upon substrate binding. The
substrate-binding site of the enzyme is located within a (beta alpha)8 TIM-barrel
domain. In the absence of substrate, this TIM-barrel domain is split apart and
the active site is accessible to solvent. When substrate binds, the barrel closes
up with the substrate along its axis and the active site becomes completely
buried. CONCLUSIONS: The closure of the active-site cavity upon substrate binding
displaces the adenosyl group of the cofactor from the central cobalt atom into
the active-site cavity. This triggers the formation of the free radical that
initiates the rearrangement reaction. The TIM-barrel domain is substantially
different from all others yet reported: in its unliganded form it is broken open,
exposing the small hydrophilic sidechains which fill the centre. The typical
barrel structure is only formed when substrate is bound.
PMID- 9655824
TI - A mixed disulfide bond in bacterial glutathione transferase: functional and
evolutionary implications.
AB - BACKGROUND: Glutathione S-transferases (GSTs) are a multifunctional group of
enzymes, widely distributed in aerobic organisms, that have a critical role in
the cellular detoxification process. Unlike their mammalian counterparts,
bacterial GSTs often catalyze quite specific reactions, suggesting that their
roles in bacteria might be different. The GST from Proteus mirabilis (PmGST B1-1)
is known to bind certain antibiotics tightly and reduce the antimicrobial
activity of beta-lactam drugs. Hence, bacterial GSTs may play a part in bacterial
resistance towards antibiotics and are the subject of intense interest. RESULTS:
Here we present the structure of a bacterial GST, PmGST B1-1, which has been
determined from two different crystal forms. The enzyme adopts the canonical GST
fold although it shares less than 20% sequence identity with GSTs from higher
organisms. The most surprising aspect of the structure is the observation that
the substrate, glutathione, is covalently bound to Cys 10 of the enzyme. In
addition, the highly structurally conserved N-terminal domain is found to have an
additional beta strand. CONCLUSIONS: The crystal structure of PmGST B1-1 has
highlighted the importance of a cysteine residue in the catalytic cycle. Sequence
analyses suggest that a number of other GSTs share this property, leading us to
propose a new class of GSTs - the beta class. The data suggest that the in vivo
role of the beta class GSTs could be as metabolic or redox enzymes rather than
conjugating enzymes. Compelling evidence is presented that the theta class of
GSTs evolved from an ancestral member of the thioredoxin superfamily.
PMID- 9655825
TI - Drug design against a shifting target: a structural basis for resistance to
inhibitors in a variant of influenza virus neuraminidase.
AB - BACKGROUND: Inhibitors of the influenza virus neuraminidase have been shown to be
effective antiviral agents in humans. Several studies have reported the selection
of novel influenza strains when the virus is cultured with neuraminidase
inhibitors in vitro. These resistant viruses have mutations either in the
neuraminidase or in the viral haemagglutinin. Inhibitors in which the glycerol
sidechain at position 6 of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid
(Neu5Ac2en) has been replaced by carboxamide-linked hydrophobic substituents have
recently been reported and shown to select neuraminidase variants. This study
seeks to clarify the structural and functional consequences of replacing the
glycerol sidechain of the inhibitor with other chemical constituents. RESULTS:
The neuraminidase variant Arg292-->Lys is modified in one of three arginine
residues that encircle the carboxylate group of the substrate. The structure of
this variant in complex with the carboxamide inhibitor used for its selection,
and with other Neu5Ac2en analogues, is reported here at high resolution. The
structural consequences of the mutation correlate with altered inhibitory
activity of the compounds compared with wild-type neuraminidase. CONCLUSIONS: The
Arg292-->Lys variant of influenza neuraminidase affects the binding of substrate
by modification of the interaction with the substrate carboxylate. This may be
one of the structural correlates of the reduced enzyme activity of the variant.
Inhibitors that have replacements for the glycerol at position 6 are further
affected in the Arg292-->Lys variant because of structural changes in the binding
site that apparently raise the energy barrier for the conformational change in
the enzyme required to accommodate such inhibitors. These results provide
evidence that a general strategy for drug design when the target has a high
mutation frequency is to design the inhibitor to be as closely related as
possible to the natural ligands of the target.
PMID- 9655826
TI - The structure of a methylated tetraloop in 16S ribosomal RNA.
AB - BACKGROUND: Ribosomal RNAs contain many modified nucleotides. The functions of
these nucleotides are poorly understood and few of them are strongly conserved.
The final stem loop in 16S-like rRNAs is an exception in both regards. In both
prokaryotes and eukaryotes, the tetranucleotide loop that caps the 3'-terminal
stem contains two N6, N6-dimethyladenosine residues. The sequence and pattern of
methylation are conserved within the loop, and there is evidence that these
methylated nucleotides play an important role in subunit association and the
initiation of protein synthesis. Because of the integral role that helix 45 plays
in ribosome function, it is important to know what consequences these methylated
nucleotides have on its structure. RESULTS: We have solved the solution structure
of a 14-nucleotide analog of the terminal stem loop of bacterial 16S rRNA, which
contains N2-methylguanosine as well as two N6,N6-dimethyladenosines. CONCLUSIONS:
The methylation of the 16S rRNA stem loop completely alters its conformation,
which would otherwise be a GNRA tetraloop. It is likely that the conformation of
this loop is crucial for its function, having implications for its interaction
with ribosomal subunits and its role in the initiation of protein synthesis.
PMID- 9655827
TI - Crystal structures of reduced and oxidized DsbA: investigation of domain motion
and thiolate stabilization.
AB - BACKGROUND: The redox proteins that incorporate a thioredoxin fold have diverse
properties and functions. The bacterial protein-folding factor DsbA is the most
oxidizing of the thioredoxin family. DsbA catalyzes disulfide-bond formation
during the folding of secreted proteins. The extremely oxidizing nature of DsbA
has been proposed to result from either domain motion or stabilizing active-site
interactions in the reduced form. In the domain motion model, hinge bending
between the two domains of DsbA occurs as a result of redox-related
conformational changes. RESULTS: We have determined the crystal structures of
reduced and oxidized DsbA in the same crystal form and at the same pH (5.6). The
crystal structure of a lower pH form of oxidized DsbA has also been determined
(pH 5.0). These new crystal structures of DsbA, and the previously determined
structure of oxidized DsbA at pH 6.5, provide the foundation for analysis of
structural changes that occur upon reduction of the active-site disulfide bond.
CONCLUSIONS: The structures of reduced and oxidized DsbA reveal that hinge
bending motions do occur between the two domains. These motions are independent
of redox state, however, and therefore do not contribute to the energetic
differences between the two redox states. Instead, the observed domain motion is
proposed to be a consequence of substrate binding. Furthermore, DsbA's highly
oxidizing nature is a result of hydrogen bond, electrostatic and helix-dipole
interactions that favour the thiolate over the disulfide at the active site.
PMID- 9655828
TI - Validation tools: can they indicate the information content of macromolecular
crystal structures?
AB - The explosive increase in the number of published three-dimensionsal structures
of macromolecules determined by X-ray analysis places a responsibility on
experimentalists, referees and curators of databases to ensure correspondence
between the structure parameters and data. Validation tools will evolve as more
appropriate statistical techniques and new information, such as that from
proteins analysed at atomic resolution, becomes available.
PMID- 9655829
TI - Mapping protein-ligand interactions by footprinting, a radical idea.
PMID- 9655830
TI - Lactate dehydrogenase from the hyperthermophilic bacterium thermotoga maritima:
the crystal structure at 2.1 A resolution reveals strategies for intrinsic
protein stabilization.
AB - BACKGROUND: L(+)-Lactate dehydrogenase (LDH) catalyzes the last step in anaerobic
glycolysis, the conversion of pyruvate to lactate, with the concomitant oxidation
of NADH. Extensive physicochemical and structural investigations of LDHs from
both mesophilic and thermophilic organisms have been undertaken in order to study
the temperature adaptation of proteins. In this study we aimed to determine the
high-resolution structure of LDH from the hyperthermophilic bacterium Thermotoga
maritima (TmLDH), the most thermostable LDH to be isolated so far. It was hoped
that the structure of TmLDH would serve as a model system to reveal strategies of
protein stabilization at temperatures near the boiling point of water. RESULTS:
The crystal structure of the extremely thermostable TmLDH has been determined at
2.1 A resolution as a quaternary complex with the cofactor NADH, the allosteric
activator fructose-1,6-bisphosphate, and the substrate analog oxamate. The
structure of TmLDH was solved by Patterson search methods using a homology-based
model as a search probe. The native tetramer shows perfect 222 symmetry.
Structural comparisons with five LDHs from mesophilic and moderately thermophilic
organisms and with other ultrastable enzymes from T. maritima reveal possible
strategies of protein thermostabilization. CONCLUSIONS: Structural analysis of
TmLDH and comparison of the enzyme to moderately thermophilic and mesophilic
homologs reveals a strong conservation of both the three-dimensional fold and the
catalytic mechanism. Going from lower to higher physiological temperatures a
variety of structural differences can be observed: an increased number of
intrasubunit ion pairs; a decrease of the ratio of hydrophobic to charged surface
area, mainly caused by an increased number of arginine and glutamate sidechains
on the protein surface; an increased secondary structure content including an
additional unique 'thermohelix' (alphaT) in TmLDH; more tightly bound
intersubunit contacts mainly based on hydrophobic interactions; and a decrease in
both the number and the total volume of internal cavities. Similar strategies for
thermal adaptation can be observed in other enzymes from T. maritima.
PMID- 9655831
TI - The structure and function of antiamoebin I, a proline-rich membrane-active
polypeptide.
AB - BACKGROUND: Antiamoebin is a member of the peptaibol family of polypeptides and
has a unique antibiotic activity: it acts as an antiamoebic agent, but does not
effectively haemolyze erythrocytes even though it does exhibit membrane-modifying
activity. RESULTS: The structure of antiamoebin I has been determined by X-ray
crystallography at 1.4 A resolution. The molecule forms a helical structure,
which, as a result of the presence of a number of proline and hydroxyproline
residues, has a deep bend in the middle. Circular dichroism spectroscopy, single
channel conductance studies and fluorescence diffusion studies suggest a mode of
ion transport that is entirely different from that of the other two members of
the peptaibol family (alamethicin and zervamicin) whose structures and functions
have been examined in detail. CONCLUSIONS: The structure of the polypeptide has
been determined and a functional model for its mode of action in membranes is
presented. Although under some conditions antiamoebin may form ion channels,
unlike the closely related alamethicin and zervamicin polypeptides, its major
membrane-modifying activity appears to be as an ion carrier.
PMID- 9655832
TI - The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals
novel features important for integrin recognition.
AB - BACKGROUND: Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is a cell
adhesion molecule that is expressed on the endothelium in mucosa, and guides the
specific homing of lymphocytes into mucosal tissues. MAdCAM-1 belongs to a
subclass of the immunoglobulin superfamily (IgSF), the members of which are
ligands for integrins. Human MAdCAM-1 has a unique dual function compared to
other members in the same subclass in that it binds both the integrin
alpha4beta7, through its two IgSF domains, and a selectin expressed on
leukocytes, via carbohydrate sidechains. The structure determination of the two
IgSF domains and comparison to the N-terminal two-domain structures of vascular
cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecules (ICAM-1
and ICAM-2) allow us to assess the molecular basis of the interactions between
integrins and their preferred ligands. RESULTS: The crystal structure of a
fragment containing the two IgSF domains of human MAdCAM-1 has been determined to
2.2 A resolution. The structure of MAdCAM-1 reveals two separate integrin
recognition motifs. The key integrin-binding residue, Asp42, resides in the CD
loop of domain 1; a buried arginine residue (Arg70) plays a critical role in
maintaining the conformation of this loop. The second binding site is associated
with an unusual long D strand in domain 2. The D and E strands extend beyond the
main body of the domain, forming a negatively charged beta ribbon unique to
MAdCAM-1. This ribbon is located on the same face as the key aspartate residue in
domain 1, consistent with evidence that it is involved in integrin binding.
CONCLUSIONS: The structural comparison of MAdCAM-1 to other members of the same
IgSF subclass reveals some interesting features. Firstly, MAdCAM-1, like VCAM-1,
has the key integrin-binding residue located on the protruding CD loop of domain
1 and binds to an integrin that lacks an I domain. This is in contrast to ICAM-1
and ICAM-2 where the key residue is located at the end of the C strand on a flat
surface and which bind to integrins that contain I domains. Secondly,
architectural differences in the CD loops of MAdCAM-1 and VCAM-1 cause an 8 A
shift in position of the critical aspartate residue, and may partly determine
their binding preference for different integrins. Finally, the unusual charge
distribution of the two-domain fragment of MAdCAM-1 is predicted to orient the
molecule optimally for integrin binding on the top of its long mucin-like stalk.
PMID- 9655833
TI - Functional universality and evolutionary diversity: insights from the structure
of the ribosome.
AB - The structure of the mammalian ribosome, reconstructed at 25 A resolution, has
added a new dimension to our current knowledge, as it manifests the conservation
and universality of the ribosome in respect to its primary tasks in protein
biosynthesis. A combined approach to study of the ribosome, using X-ray
crystallography and electron microscopy, may further improve our understanding of
ribosome function in the future.
PMID- 9655835
TI - Mechanisms of lysophosphatidylcholine-induced increase in intracellular calcium
in rat cardiomyocytes.
AB - Previous reports have demonstrated that lysophosphatidylcholine (LPC) increases
the intracellular concentration of calcium ([Ca++]i) in the heart; however, the
mechanisms responsible for this increase are not clear. We examined the effect of
exogenous LPC on [Ca++]i in freshly isolated cardiomyocytes from adult rats. Our
results showed that LPC elevated the [Ca++]i in a dose-dependent (2.5-10 microM)
manner. The LPC (10 microM)-induced increase in [Ca++]i was augmented upon
increasing the concentration of extracellular Ca++ and was abolished by the
removal of Ca++ from the medium. Preincubation of cardiomyocytes with sarcolemmal
L-type Ca++ channel blocker, verapamil, did not affect the LPC-evoked increase in
[Ca++]i significantly. On the other hand, ouabain, a Na(+)-K+ ATPase inhibitor,
and low concentrations of extracellular Na+ enhanced the LPC response. The LPC
induced increase in [Ca++]i was attenuated significantly by the inhibitors of
Na(+)-Ca++ exchanger such as Ni++ and amiloride. Depletion of the sarcoplasmic
reticulum (SR) Ca++ stores by low micromolar concentrations of ryanodine (a SR
Ca(++)-release channel activator) or by thapsigargin (a SR Ca(++)-pump ATPase
inhibitor) depressed the LPC-mediated increase in [Ca++]i. Combined blockade of
Na(+)-Ca++ exchanger and inhibition of SR Ca(++)-pump or ryanodine receptor had
an additive effect on the LPC response. These observations suggest that the
increase in [Ca++]i induced by LPC depends on both Ca(++)-influx from the
extracellular space and Ca(++)-release from the SR stores. Furthermore, Na(+)
Ca++ exchange plays a critical role in the LPC-mediated entry of Ca++ into
cardiomyocytes.
PMID- 9655836
TI - Ionic mechanism of ibutilide in human atrium: evidence for a drug-induced Na+
current through a nifedipine inhibited inward channel.
AB - This study examined the ionic mechanism of ibutilide, a class III antiarrhythmic
in clinical use, on freshly isolated human atrial cells. Cells had resting
potentials of -71.4 +/- 2.4 mV, action potentials with overshoot of 36.8 +/- 1.8
mV, duration of 265 +/- 89 msec at 90% repolarization and slow repolarization (n
= 16). Ibutilide, at 10(-7) M, markedly increased action potential duration. Four
types of outward currents were detected: Ito, Iso, a delayed rectifier and IK1.
Ibutilide had no inhibitory effect on these outward currents at 10(-7) M (n =
28). In K(+)-free solutions and -40 mV holding potential, mean peak inward
current at 20 mV was -1478 +/- 103 pA (n = 12). Ibutilide increased this current
to -2347 +/- 75 pA at 10(-7) M, with half maximal effect (Kd) of 0.1 to 0.9 nM
between -10 and +40 mV (n = 21). At similar concentrations, the drug increased
APD, with Kd of 0.7 and 0.23 nM at 70 and 90% repolarization, respectively (n =
8). Ibutilide shifted the mid-point of the steady-state inactivation curve from
21 to -12.2 mV (n = 6), and reduced current decline during repetitive
depolarization (n = 5). The drug induced inward current was carried by Na+o
through a nifedipine inhibited inward channel because Na+o removal eliminated the
effect, and nifedipine abolished the inward current and the drug induced APD
prolongation. We propose that a Na+ current through the L-type Ca++ channel
mediates ibutilide's potent clinical class III antiarrhythmic action.
PMID- 9655837
TI - Trimetazidine counteracts the hepatic injury associated with ischemia-reperfusion
by preserving mitochondrial function.
AB - Recent studies suggest a crucial role played by mitochondria in the pathogenesis
of ischemia-reperfusion injury. This study was conducted to clarify the role of
trimetazidine, a cellular anti-ischemic agent, on mitochondria isolated from rat
liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion.
Rats were divided into groups, pretreated with different doses of trimetazidine
(5, 10 and 20 mg/kg/day) or saline and subjected to the ischemia-reperfusion
process; another group served as the sham-operated controls. Alanine
aminotransferase and aspartate aminotransferase activities and hepatocyte ATP
content, bile flow and mitochondrial functions were assessed. Ischemia
reperfusion caused membrane leakage from hepatocytes and a decrease in ATP
content and in bile flow. These effects were well correlated with alterations in
mitochondrial function, namely, decrease in ATP synthesis, NAD(P)H level and
mitochondrial membrane potential and generation of mitochondrial permeability
transition. The pretreatment of rats with trimetazidine prevented these ischemia
reperfusion deleterious effects at both the cellular and mitochondrial level in a
dose-dependent manner. It is concluded that trimetazidine at an optimal dosage of
10 mg/kg/day protects mitochondria against the deleterious effects of ischemia
reperfusion. This protective effect appears to be the key factor through which
this drug exerts its cytoprotective activity.
PMID- 9655838
TI - Pharmacodynamic activities of ciprofloxacin and sparfloxacin in a murine
pneumococcal pneumonia model: relevance for drug efficacy.
AB - We looked for associations between pharmacokinetic (Pk) and pharmacodynamic (Pd)
parameters of ciprofloxacin (CPFX) and sparfloxacin (SPFX) and the in vivo
efficacy of these antimicrobials in an immunocompetent mouse model of severe
Streptococcus pneumoniae pneumonia. Bacterial killing curves recorded in the
lungs during the 24 h after single subcutaneous injections of the
fluoroquinolones (FQs) in doses ranging from 6.25 to 200 mg/kg were compared with
mean Pk/Pd parameters in the serum of the same mice. The impact of the dosing
interval on the antimicrobial dose response was evaluated based on the survival
of mice treated for 3 days with CPFX (25-200 mg/kg) or SPFX (6.25-50 mg/kg)
administered at various intervals from 3 to 24 h. Bacterial killing curves showed
that the maximal bacterial decrease achieved in the lungs was correlated,
similarly for both FQs, with the area under the curve (AUC) above the minimal
inhibitory concentration (MIC) (overall correlation: r = 0.968, P < 10(-4)). CPX
attained higher maximal bactericidal effect values, a steeper killing slope and a
shorter time to maximal bactericidal effect in comparison with SPX for the
highest doses tested. The lower MIC of SPFX compared with CPFX (0.25 vs. 0.75
microgram/ml) and its higher AUC/dose ratio (resulting from a lower serum peak
but a longer half-life) translated into a greater area under the bactericidal
curve. In the dose fractionation experiments, the Pk/Pd parameter most closely
correlated with the survival rate for both FQs was the daily AUC/MIC ratio (r =
0.976, P < 10(-4)). When the AUC/MIC ratio was greater than 160, the probability
of a clinical cure was 100%, independently of the dosage schedule.
PMID- 9655840
TI - Involvement of dopaminergic system in phencyclidine-induced place preference in
mice pretreated with phencyclidine repeatedly.
AB - In the conditioned place preference test, phencyclidine (PCP) produces place
aversion in naive rats, whereas PCP produces place preference in rats treated
with PCP repeatedly. Although the PCP-induced place aversion is thought to
involve the serotonergic system, the mechanisms of the PCP-induced place
preference are unclear. We investigated whether the dopaminergic system is
involved in place preference induced by PCP in mice repeatedly treated with PCP,
because it is well known that the dopaminergic system plays an important role in
the rewarding effect of drugs. PCP (2-8 mg/kg s.c.) induced a dose-dependent
place aversion in naive mice, whereas PCP (2-8 mg/kg s.c.) induced a dose
dependent place preference in mice pretreated with PCP (10 mg/kg/day s.c.) for 28
days. The place preference induced by PCP (8 mg/kg s.c.) was attenuated
significantly by alpha-methyl-rho-tyrosine (100 mg/kg i.p.), a tyrosine
hydroxylase inhibitor, 6-hydroxydopamine (100 micrograms/mouse i.c.v.), a
dopaminergic neurotoxin, and R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
tetrahydro-1H-3-benza zepine (0.5 mg/kg s.c.), a dopamine D1 receptor antagonist.
These agents themselves produced neither the place preference nor aversion. In
contrast to the attenuating effects of these agents, N-(2-chloroethyl)-N-ethyl-2
bromobenzylamine (30 mg/kg i.p.), a noradrenergic neurotoxin, ritanserin (1 mg/kg
i.p.), a serotonin2 receptor antagonist, and (-) sulpiride (50 and 100 mg/kg
i.p.), a dopamine D2 receptor antagonist, failed to affect the PCP-induced place
preference. In mice pretreated with methamphetamine (1 mg/kg/day s.c.) for 14
days, PCP (8 mg/kg s.c.) induced the place preference, but not aversion. These
results demonstrate that the PCP-induced place preference depends on
dopaminergic, but not on serotonergic and noradrenergic, neuronal systems and
suggest a role for D1 receptors in the mediation of the PCP-induced place
preference.
PMID- 9655839
TI - Protein kinase C does not mediate phenylephrine-induced down-regulation of Madin
Darby canine kidney cell alpha-1B adrenoceptors.
AB - We examined the down-regulation of alpha-1B adrenoceptors in Madin-Darby canine
kidney D1 (MDCK) cells with an emphasis on a possible role of protein kinase C.
The alpha-1 adrenoceptor agonist phenylephrine (1-100 microM) concentration
dependently down-regulated alpha-1B adrenoceptors in MDCK cells. Down-regulation
by 100 microM phenylephrine was detectable after 2 hr and maximal after 8 to 24
hr. The receptor down-regulation was accompanied by a decrease in phenylephrine
stimulated inositol phosphate formation but not by an altered expression of
immunodetectable Gq/11 alpha subunits. Even though alpha-1B adrenoceptor and P2
purinergic receptor stimulation promote prostaglandin E2 formation, receptor down
regulation was not prevented by indomethacin (10 microM) treatment but was partly
mimicked by treatment with the purinergic receptor agonists adenosine-5'-O-(3
thio)triphosphate and 2-methylthio-ATP (300 microM each). Phorbol-12-myristate-13
acetate (1-100 nM) concentration-dependently down-regulated MDCK alpha-1B
adrenoceptors to a greater extent than did phenylephrine. Three protein kinase C
inhibitors, H7 (100 microM), staurosporine (100 nM) and KT5926 (1 microM),
markedly attenuated receptor down-regulation promoted by phorbol ester but did
not affect that by phenylephrine. Two inhibitors of Ca++/calmodulin protein
kinase pathways, KT5926 (1 microM) and W-7 (30 microM), also failed to prevent
phenylephrine-induced down-regulation of alpha-1B adrenoceptors. We conclude that
agonist-induced down-regulation of MDCK cell alpha-1B adrenoceptors is mimicked
by a protein kinase C-activating phorbol ester but that the second messenger
kinases protein kinase C and Ca++/calmodulin protein kinase do not mediate
agonist-induced down-regulation of the alpha-1B adrenoceptor.
PMID- 9655841
TI - Relation of cysteine conjugate nephrotoxicity to transport by the basolateral
organic anion transport system in isolated S2 segments of rabbit proximal renal
tubules.
AB - We examined basolateral transport of the radiolabeled zwitterionic nephrotoxic
cysteine S-conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), inhibition of such
transport and the effects of inhibition of transport on the toxicity produced by
DCVC in isolated S2 segments of rabbit proximal tubules. High concentrations of
unlabeled DCVC itself and an unlabeled nontoxic cysteine S-conjugate, S-(2
benzothiazole)-L-cysteine cis-inhibited the basolateral uptake of radiolabeled
DCVC by approximately 80 to 85%. High concentrations of para-aminohippurate, the
prototype substrate for the basolateral organic anion transport system, and
probenecid, a well-known inhibitor of basolateral organic anion transport, cis
inhibited the basolateral uptake of radiolabeled DCVC by approximately 70%,
whereas a high concentration of L-phenylalanine had little effect. High
concentrations of S-(2-benzothiazole)-L-cysteine and para-aminohippurate in the
bathing medium with DCVC inhibited the loss of 86Rb (used as a K+ surrogate to
measure toxicity) from S2 segments produced by DCVC alone to approximately the
same extent as they inhibited uptake of DCVC. Under the same circumstances,
probenecid completely inhibited 86Rb loss. These data indicate that in rabbit
proximal renal S2 tubules basolateral entry of DCVC can occur to a major extent
via the organic anion transport pathway and that inhibition of such entry can
reduce toxicity to approximately the same extent that entry is reduced. They also
suggest that probenecid provides additional protection from DCVC toxicity.
PMID- 9655842
TI - Self-administration of cocaine-heroin combinations by rhesus monkeys: antagonism
by naltrexone.
AB - Low, nonreinforcing doses of heroin have been shown to shift the dose-response
function of cocaine leftward in rhesus monkeys trained under a progressive-ratio
schedule of i.v. drug injection. Our study sought to determine 1) whether a
reciprocal enhancement of heroin self-administration would be observed when
heroin was combined with low, nonreinforcing doses of cocaine, and 2) whether
self-administration of cocaine-heroin combinations could be antagonized by the
opioid antagonist naltrexone. Rhesus monkeys (n = 4) were prepared with i.v.
catheters and trained to self-administer cocaine under a progressive-ratio
schedule. The initial response requirement of this schedule was fixed-ratio 120,
which doubled across the session to a maximum of 1920. Injections were separated
by a 30-min time out. Cocaine dose-response functions (6.4-100
micrograms/kg/injection) for injections/session and breakpoints were monophasic,
i.e., increased with dose until responding reached a maximum. Heroin dose
response functions (1.6-25 micrograms/kg/ injection) either increased to a peak
and then decreased or reached an asymptote. When nonreinforcing doses of cocaine
(3.2-25 micrograms/kg/injection) were combined with heroin, the heroin dose
response function was shifted to the left, without change in maximum
injections/session. Pressession treatments with naltrexone (3.2-1600
micrograms/kg, i.m., 10-min presession) antagonized self-administration of heroin
and heroin + cocaine combinations in a dose-dependent fashion. However,
naltrexone treatment had no effect on cocaine self-administration. Antagonism by
naltrexone of self-administration of heroin and heroin + cocaine was surmounted
by increasing the dose of heroin either alone or in the heroin + cocaine
combination. In vivo apparent pA2 and pKB analyses of these data revealed values
of approximately 8.0, consistent with a role for mu opioid receptors in the self
administration of heroin and cocaine-heroin (i.e., "speedball") combinations.
PMID- 9655843
TI - C-type natriuretic peptide increases myocardial contractility and sinus rate
mediated by guanylyl cyclase-linked natriuretic peptide receptors in isolated,
blood-perfused dog heart preparations.
AB - There are no available data on the direct effect of C-type natriuretic peptide
(CNP) and brain natriuretic peptide (BNP) on the myocardial contractility in
mammalian hearts. Thus we studied the inotropic and chronotropic effects of CNP
22 and BNP-32 compared with those of atrial natriuretic peptide (ANP)-28 using
the isolated, blood-perfused canine right atrial or left ventricular
preparations. CNP increased the atrial contractile force in a dose-dependent
manner with a small increase in sinus rate in isolated atria, whereas neither ANP
nor BNP changed atrial force and rate. CNP but not BNP also increased the
ventricular contractile force in isolated ventricles. Pretreatment with a high
dose (3 nmol) of CNP attenuated the positive inotropic response to CNP at a low
dose (1 nmol) but not to norepinephrine. A guanylyl cyclase-linked natriuretic
peptide receptor antagonist, HS-142-1, inhibited the increases in atrial
contractile force and sinus rate in response to CNP, but it did not affect the
positive cardiac responses to norepinephrine. Propranolol did not block the
positive cardiac responses to CNP. 3-Isobutyl-1-methylxanthine in rates of 0.6 to
1.3 mumol/ min attenuated the CNP-induced positive inotropic responses, when it
potentiated the positive inotropic response to norepinephrine. On the other hand,
parasympathetic nerve stimulation attenuated the positive cardiac responses to
CNP and norepinephrine. These results demonstrate that CNP increases myocardial
contractile force with a small increase in sinus rate mediated by guanylyl
cyclase-linked natriuretic peptide receptors, probably type B receptors in the
dog heart, and suggest that the positive inotropic response to CNP is influenced
by the cyclic adenosine 3',5'-monophosphate-dependent signal transduction.
PMID- 9655844
TI - First evidence of otoprotection against carboplatin-induced hearing loss with a
two-compartment system in patients with central nervous system malignancy using
sodium thiosulfate.
AB - Sodium thiosulfate (STS) provides protection against carboplatin-induced
ototoxicity in an animal model. The purpose of this study was to determine the
STS dose required for otoprotection, in patients with malignant brain tumors
treated with carboplatin in conjunction with osmotic blood-brain barrier
disruption. Twenty-nine patients received STS intravenously 2 hr after
carboplatin. Doses were escalated from 4 g/m2 to 8, 12, 16 and 20 g/m2 on
consecutive months. Audiologic assessment was performed at baseline and monthly.
The audiograms were compared with those of 19 similarly treated historical
control patients who did not receive STS. The incidence of ototoxicity in the
historical control group of patients was 79% (15/19). This group had an average
loss of 20.8 +/- 5.9 dB (n = 19) at 8 kHz after one treatment with carboplatin,
whereas the STS treatment group lost only 3.7 +/- 2 dB (n = 15) after one
treatment. This difference was statistically significant as assessed by Student's
t test (P < .05). Furthermore, patients in the STS treatment group with excellent
base-line hearing showed little change in hearing thresholds at 8 kHz after the
second treatment (8.0 +/- 8.3 dB) (n = 5) compared with the historical control
patients with excellent base-line hearing, (40.5 +/- 8.6 dB) (n = 11). Our data
support that doses of 16 or 20 g/m2 of STS decrease carboplatin-induced hearing
loss without central nervous system entry. Clinical demonstration of an
otoprotective effect with a two-compartment system to prevent drug-induced
hearing loss, while preserving central nervous system cytotoxicity, has not been
reported previously.
PMID- 9655845
TI - Creation of a constitutively activated state of the 5-hydroxytryptamine2A
receptor by site-directed mutagenesis: inverse agonist activity of antipsychotic
drugs.
AB - Single amino acid mutations in the third intracellular loop, as well as other
domains of G protein-coupled receptors, have been shown to confer drastic changes
in receptor properties and have been postulated to be responsible for various
disease states. To determine whether an amino acid mutation can confer dramatic
alterations in the 5-hydroxytryptamine2A (5-HT2A) receptor, we mutated amino acid
322 to lysine (C322K), glutamate (C322E) or arginine (C322R). Transient
expression of the mutant receptors revealed properties associated with
constitutive activity. Radioligand binding studies revealed an increase in 5-HT
affinity from 293 nM (native) to 86 nM (C322E), 25 nM (C322K) and 11 nM (C322R).
5-HT potency for stimulation of inositol phosphate production increased from 152
nM (native) to 61 nM (C322E) and 25 nM (C322K). Basal inositol phosphate levels
in COS-7 cells expressing C322K and C322E mutant receptors were 8-fold and 4-fold
higher, respectively, than cells expressing native 5-HT2A receptors. Basal levels
of inositol phosphate stimulated by C322K receptors represented 48% of total
inositol phosphate production stimulated by native receptors in the presence of
10 microM 5-HT. Antipsychotic drugs (chlorpromazine, clozapine, haloperidol,
loxapine and risperidone) displayed inverse agonist activity by inhibiting C322K
constitutive activation of phosphatidylinositol hydrolysis. These data indicate
that amino acid 322 in the 5-HT2A receptor plays an important role in maintaining
the inactive conformation and provide further evidence that amino acid mutations
can produce profound alterations in G protein-coupled receptor activity.
PMID- 9655846
TI - Muscarinic receptors regulate extracellular glutamate levels in the rat striatum:
an in vivo microdialysis study.
AB - Regulation of extracellular glutamate levels by muscarinic receptors in the
striatum of unanesthetized rats was investigated by microdialysis. Extracellular
glutamate levels were elevated by intrastriatal perfusion of L-trans-pyrrolidine
2,4-dicarboxylic acid (L-trans-PDC), a competitive substrate of plasma membrane
excitatory amino acid transporters. The nonselective muscarinic agonist,
oxotremorine (0.5-54 microM) significantly decreased L-trans-PDC-evoked glutamate
levels in a concentration-dependent manner. Scopolamine (0.1-10 microM), a
nonselective muscarinic receptor antagonist, reversed the effect of oxotremorine,
which confirms that muscarinic receptor activation mediated the reduction of L
trans-PDC-evoked glutamate levels. In addition, scopolamine (10 microM)
significantly elevated basal extracellular glutamate levels, an effect prevented
by oxotremorine, which suggests that acetylcholine tonically regulates
glutamatergic transmission in the striatum. Previous data from this laboratory
have shown that L-trans-PDC-evoked glutamate levels are partially calcium
dependent. The present study demonstrated that attenuation of L-trans-PDC-evoked
glutamate levels by reduced calcium was not altered by oxotremorine. Therefore,
it is likely that muscarinic receptors regulate calcium-dependent glutamate
release evoked by L-trans-PDC.
PMID- 9655847
TI - Extracellular 3',5' cyclic guanosine monophosphate inhibits kainate-activated
responses in cultured mouse cerebellar neurons.
AB - The effects of extracellularly applied 3'-5' cyclic guanosine monophosphate
(cGMP) on kainate responses from cultured cerebellar granule and Purkinje neurons
were investigated using whole-cell and outside-out patch recording modes.
Cerebellar granule cell responses to kainate were not homogeneous, nor were the
effects of cGMP. Therefore, effects of cGMP are described for two groups of
granule cells categorized on the basis of the underlying channel conductance
estimated by variance analysis. Cells with high-noise kainate responses had
average channel conductances of 5 to 7 picoseimens, whereas the average
conductances of low-variance noise responses were 0.3 to 2.0 picoseimens. High
noise kainate responses were inhibited by externally applied cGMP (5-1000 microM)
in a rapidly reversible and dose-dependent manner. IC50 values were estimated at
approximately 150 microM cGMP for 25 microM kainate and approximately 500 microM
cGMP for 100 microM kainate. Evidence that cGMP-mediated inhibition of high-noise
kainate responses occurred by a competitive mechanism included the following: 1)
cGMP-mediated inhibition was overcome by increasing agonist concentration. 2) The
shape of kainate current-voltage (I-V) curves and their reversal potentials were
unchanged in cGMP. 3) Neither the estimated conductance nor the kinetics of the
kainate-activated channels was affected by cGMP. In contrast to the uniform
effects of cGMP on the high-noise kainate responses, the effects on low-noise
kainate responses were variable. Half of the low-noise kainate responses were
inhibited by cGMP to a similar extent as the high-noise responses; however, the
other 50% of cells exhibiting low-noise kainate responses appeared to be less
sensitive to the cyclic nucleotide. Moreover, cGMP coapplication decreased the
estimated conductances for some low-noise kainate responses and altered their
noise kinetics, which suggests either that cGMP-sensitive and -insensitive
kainate receptor channels are coexpressed in these cells or that cGMP-mediated
inhibition is not competitive for this subgroup of glutamate receptor channels.
Overall, these data indicate that there are direct inhibitory effects of
extracellular cGMP on a large group of excitatory synapses in the CNS--effects
that need to be taken into account when investigators utilize membrane-permeable
cGMP analogs. Whether this cGMP-mediated inhibition has a functional role in
brain is unknown.
PMID- 9655848
TI - Relaxing effects of NO donors on guinea pig trachea in vitro are mediated by
calcium-sensitive potassium channels.
AB - The relaxing effects of the nitric oxide (NO) donors 1,2,3,4-oxatriazolium,3-(3
chloro-2-methylphenyl-5-[[(4-methoxyphe nyl) sulfonyl]amino]-,hydroxide inner
salt (GEA 3268) 1,2,3,4-oxatriazolium,3-(3-chloro-2-methyphenyl-5-[methys
ulfonyl)amino]- hydroxide inner salt (GEA 5145), 3-morpholinosydnonimine (SIN-1)
and S-nitroso-N-acetylpenicillamine (SNAP) were inhibited in vitro by iberiotoxin
(IbTX) and charybdotoxin (ChTX), the two selective inhibitors of Ca(++)-activated
K+ channels (KCa) in guinea pig trachea. When studied in cumulative
concentrations in metacholine constriction, the relaxing effects of the NO donors
were inhibited by at least 70% in the presence of the toxins, with the exception
of SIN-1 in the presence of ChTX. The inhibitory effect of ChTX was less marked
than that of IbTX. This suggests that the relaxing effects of the structurally
different NO donors are mediated through KCa channels and that IbTX is more
potent than ChTX. A selective inhibitor of soluble guanylate cyclase, 1H
[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), significantly inhibited the
relaxing effects of GEA 3268 and GEA 5145 on metacholine and KCl constriction and
almost totally inhibited the relaxing effects of SIN-1 and SNAP. The inhibitor of
the delayed rectifier K+ channel current 4-aminopyridine did not influence the
relaxations of the NO donors, and under the experimental conditions of this
study, the ATP-sensitive K+ channel inhibitor glibenclamide had no effect. In
conclusion, the relaxing effects of the structurally different NO-releasing
compounds are mediated via KCa channels. However, the significance of some other
possible mechanisms unrelated to K+ channels cannot be excluded.
PMID- 9655849
TI - Effect of nitric oxide-releasing aspirin derivative on gastric functional and
ulcerogenic responses in rats: comparison with plain aspirin.
AB - The effects of a nitric oxide (NO)-releasing derivative of aspirin, NCX-4016, on
gastric functional and ulcerogenic responses in rat stomachs were examined in
comparison with those of aspirin. Topical application of aspirin (80 mM) to the
stomach markedly decreased transmucosal potential difference and slightly
increased luminal pH (acid back-diffusion) with minimal effect on mucosal blood
flow, whereas NCX-4016 caused a marked increase in mucosal blood flow with no
effect on potential difference and pH. Aspirin itself was ulcerogenic, causing
damage in the mucosa when administered p.o., and it markedly potentiated gastric
ulcerogenic response to hypothermic stress (28 degrees C-30 degrees C) with no
effect on acid secretion when given s.c. NCX-4016, however, was not ulcerogenic
by itself, did not modify the ulcerogenic response to stress and even showed a
dose-dependent protection against HCl/ethanol-induced gastric lesions. When NCX
4016 was given intragastrically to pylorus-ligated rats, a large amount of NO was
detected in both gastric contents and serum. NCX-4016 administered either p.o. or
s.c. produced an equipotent inhibition of mucosal PGE2 generation in the stomach,
as compared with aspirin. In addition, both aspirin and NCX-4016 suppressed
carrageenan-induced rat paw edema. These results suggest that, unlike aspirin,
the NO-releasing derivative of aspirin NCX-4016 neither had a topical irritating
action on the stomach nor exerted a worsening effect on gastric ulcerogenic
response to stress, but rather provided gastric protection against ethanol,
despite inhibiting cyclo-oxygenase activity and showing anti-inflammatory action
much as aspirin does. NCX-4016, probably by releasing NO, exerted protective
effects that counteracted the potential damaging effects of cyclo-oxygenase
inhibition.
PMID- 9655850
TI - Prediction of in vivo nonlinear first-pass hepatic metabolism of YM796 from in
vitro metabolic data.
AB - Recent cumulative evidence suggests the possibility of predicting the in vivo
metabolic clearance and/or hepatic availability (Fh) from in vitro metabolism
data under linear conditions. Under nonlinear conditions, however, it is
essential to consider the rate constant for the absorption (ka) for predicting Fh
after oral administration, because the time profiles for the portal vein
concentration depends on ka. In our study, we numerically solved the dispersion
model under nonlinear conditions to propose a method to predict Fh after oral
administration by taking ka into consideration. As a model compound, (S)-(-)-2,8
dimethyl-3-methylene-1-oxa-8-azaspiro [4,5] decane-L-tartrate monohydrate (YM796)
was used. After oral administration, we found that the dose-normalized AUC
(AUCoral/dose) was markedly increased in rats from 5.0 x 10(-6) to 33 x 10(-6)
hr/ml.kg as the dose increased from 1 to 10 mg/kg, whereas the same value was
relatively constant in dogs (87.7 x 10(-6) to 105 x 10(-6) hr/ml.kg at 1 to 10
mg/kg) and in humans (1260 x 10(-6) to 1768 x 10(-6) hr/ml.kg at 5 to 60
mg/body). Kinetic analysis indicated that AUCoral could be accurately predicted
at each dose if ka value was assumed as 0.07 min-1 for all animal species
examined in our study. These results suggest that it is possible to predict Fh
even if the metabolism is composed of non-linear process by considering the
absorption rate into the portal vein.
PMID- 9655851
TI - Effects of continuous alendronate treatment on bone mass and mechanical
properties in ovariectomized rats: comparison with pamidronate and etidronate in
growing rats.
AB - Alendronate is a potent inhibitor of bone resorption. To investigate the
relationship between antiresorptive activity and bone-related side effects, we
studied the effect of 2 months of daily alendronate (0.04, 0.2, 1.0 or 5.0
mg/kg/day) treatment on the strength of the femoral shaft and neck and on the
bone mass of ovariectomized rats. The p.o. administration regimen began
immediately after ovariectomy at 6 weeks of age, and the results were compared
with pamidronate (0.2, 1.0 or 5.0 mg/kg/day) or etidronate (5.0, 25.0 or 125.0
mg/kg/day) treatment. In the femoral epiphysis and neck, a preventive effect of
alendronate on loss of bone mineral density was observed at the dose of 1.0
mg/kg. The alendronate-treated group did not show significant alteration of the
breaking load or the cross-sectional shape of the femoral midshaft. Similar
results were obtained in the femoral neck strength and femoral neck geometry. In
histomorphometric analysis of tibial metaphyses, alendronate inhibited the ratio
of osteoid volume to tissue volume and the mineral apposition rate at a dose of
0.2 mg/kg compared with the ovariectomized control. In contrast, etidronate
tended to increase osteoid volume/bone volume at 125 mg/kg. From these results,
we conclude that p.o. alendronate-treatment prevented the decrease in bone
mineral density and maintained the mechanical properties of bone after
ovariectomy without impairing of bone mineralization in growing rats.
PMID- 9655852
TI - Dynorphin A as a potential endogenous ligand for four members of the opioid
receptor gene family.
AB - Dynorphin A is an endogenous opioid peptide that activates the kappa opioid
receptor (KOR) with high potency. Some studies also showed that the distribution
and functional activity of dynorphin A are not completely correlated with those
of KOR, suggesting that dynorphin A may interact with other receptors. To
investigate the possibility that dynorphin A may serve as an agonist for other
opioid receptors, we took the advantage of the cloning of the three major types
of opioid receptors, mu (MOR), delta (DOR) and KOR, and examined their affinity
for and their activation by dynorphin A. We used mammalian cells transfected with
each of the cDNA clones for the human receptors hMOR, hDOR, hKOR and showed that
dynorphin A displaced [3H]-diprenorphine binding with Ki values in the nanomolar
range at all three receptors. We also showed that, when hMOR, hDOR or hKOR was
coexpressed with a G protein-activated potassium channel in Xenopus oocytes,
dynorphin A induced a potassium current with EC50 values in the nanomolar range
for all three receptors. Furthermore, we showed that the human hORLI, an opioid
receptor-like receptor that has been identified as a novel member of the opioid
receptor gene family, displayed dynorphin A binding and functional activation.
These results indicate that dynorphin A is capable of binding to and functional
activation of all members of the opioid receptor family, suggesting that, as a
potential endogenous agonist, its activity in humans may involve interaction with
other members of the opioid receptor family in addition to kappa receptors.
PMID- 9655853
TI - Physiological red blood cell kinetic model to explain the apparent discrepancy
between adenosine breakdown inhibition and nucleoside transporter occupancy of
draflazine.
AB - A physiological red blood cell (RBC) kinetic model is proposed for the adenosine
(ADO) transport into erythrocytes and its subsequent intracellular deamination
into inactive inosine (INO) and further breakdown into hypoxanthine (HYPO). The
model and its parameters were based on previous studies investigating the
kinetics of the biochemical mechanism of uptake and metabolism of ADO in human
erythrocytes. Application of the model for simulations of the breakdown of ADO in
a RBC suspension revealed that the predicted adenosine breakdown inhibition (ABI)
of draflazine corresponded well with the ABI measured ex vivo. The model
definitely explained the apparent discrepancy between the ex vivo measured ABI
and the nucleoside transporter occupancy of draflazine. Intracellular deamination
of ADO rather than its transport by the nucleoside transporter is the rate
limiting step in the overall catabolism of ADO. Consequently, at least 90%
occupancy of the transporter by draflazine is required to inhibit adenosine
breakdown ex vivo substantially. Simulations on basis of the validated model were
performed to evaluate the ABI for different experimental conditions and to mimic
the clinical situation. The latter may be very helpful for the design of optimal
dosing schemes of draflazine. It was demonstrated that the short half-life of
released ADO was prolonged substantially in a dose-related manner after a
continuous infusion of draflazine. Finally, the previously found different
sigmoidal Emax relationships between the measured ABI and the concentrations of
draflazine in plasma and whole blood could be explained by the ADO transport and
breakdown RBC kinetic model and the capacity-limited specific RBC binding
characteristics of draflazine.
PMID- 9655854
TI - The role of peripheral mu opioid receptors in the modulation of capsaicin-induced
thermal nociception in rhesus monkeys.
AB - Capsaicin produces burning pain, followed by nociceptive responses, such as
allodynia and hyperalgesia in humans and rodents. In the present study, when
administered subcutaneously into the tail of rhesus monkeys, capsaicin (0.01-0.32
mg) dose-dependently produced thermal allodynia manifested as reduced tail
withdrawal latencies in 46 degrees C water, from a maximum value of 20 sec to
approximately 2 sec. Coadministration of selective mu opioid agonists, fentanyl
(0.003-0.1 mg) and (D-Ala2,N-Me-Phe4, Gly5-ol)-enkephalin (0.001-0.03 mg), dose
dependently inhibited capsaicin-induced allodynia. This local antinociception was
antagonized by small doses of opioid antagonists, quadazocine (0.03 mg) and
quaternary naltrexone (1 mg), applied locally in the tail. However, these doses
of antagonists injected s.c. in the back did not antagonize local fentanyl.
Comparing the relative potency of either agonist or antagonist after local and
systemic administration confirmed that the site of action of locally applied mu
opioid agonists is in the tail. These results provide evidence that activation of
peripheral mu opioid receptors can diminish capsaicin-induced allodynia in
primates. This experimental pain model could be a useful tool for evaluating
peripherally acting antinociceptive agents without central side effects and
enhance new approaches to the treatment of inflammatory pain.
PMID- 9655855
TI - Detailed mapping of ochratoxin A reabsorption along the rat nephron in vivo: the
nephrotoxin can be reabsorbed in all nephron segments by different mechanisms.
AB - Ochratoxin A (OTA) is a widespread nephrotoxin excreted to a substantial degree
via the kidney. Previously we showed that [3H]OTA can be reabsorbed along the rat
nephron in vivo (Zingerle et al., 1997). In this study we investigated in detail
the contribution of different nephron segments to [3H]OTA reabsorption and
determined the possible mechanisms involved by microinfusion and microperfusion
experiments. At pH 6 (approximately 94% of OTA neutral), OTA is reabsorbed in all
nephron segments investigated. The estimated fractional reabsorptions (FR) at a
tubular load of 20 fmol/min are: proximal convoluted tubule (PCT), 14.8%;
proximal straight tubule (PST), 27.4%; ascending limb of Henle's loop (ALH),
13.6%; distal tubule (DT), 11.6%; collecting duct (CD), 24.6%; terminal CD,
22.0%. At pH 8 (approximately 10% of OTA neutral) FR are as follows: PCT, 0%;
PST, 25.9%; ALH, 14.0%; DT, 3.2%; CD, 8.2%. Thus, OTA reabsorption in PST and ALH
in pH-independent. Reabsorption in PST but not in DT or CD was inhibited by
sulfobromophthalein, a substrate of the apical organic anion carrier. L
Phenylalanine did not reduce OTA reabsorption. After intravenous injection of
unlabeled OTA, resulting in a plasma concentration of approximately 10(-5) mol/l,
the FR of [3H]OTA during early proximal microinfusion was reduced slightly. From
our results we conclude: 1) OTA can be reabsorbed in all nephron segments
investigated. 2) Under physiological conditions the predominant sites of
reabsorption are PST, ALH and terminal CD. 3) Reabsorption in PST and ALH is not
pH-dependent. 4) pH-independent reabsorption in PST is mediated by the apical
organic anion transporter (OAT-K1), whereas pH-dependent reabsorption in PCT is
mediated by H(+)-dipeptide cotransporter(s). 5) Reabsorption also takes place
during natural exposure, i.e., when OTA is present in plasma and renal tissue. 6)
The high FR in ALH and CD explains, at least in part, the preferential impairment
of postproximal functions and the accumulation in renal inner medulla and papila.
PMID- 9655856
TI - Sigma ligands stimulate the electrical activity of frog pituitary melanotrope
cells through a G-protein-dependent inhibition of potassium conductances.
AB - We have investigated the effects of sigma ligands [1,3-di(2-tolyl)guanidine (DTG)
and (+)-pentazocine] on the electrical activity of cultured frog pituitary
melanotrope cells by using the patch-clamp technique. DTG and (+)-pentazocine (10
microM each) induced a reversible depolarization associated with an increase in
membrane resistance and action potential firing. In voltage-clamp experiments,
DTG and (+)-pentazocine elicited inward currents whose intensity augmented with
membrane depolarization. The currents vanished or reversed between -90 and -100
mV, at values close to the K+ equilibrium potential (E(K)+ = -102 mV). DTG (2-500
microM) and (+)-pentazocine (0.2-200 microM) reduced the outward delayed
rectifier K+ current [IK (V)] in a dose-dependent manner with EC50 of 64 and 37
microM, respectively. In contrast, naloxone (50 microM) and pirenzepine (10
microM) did not affect the sigma ligand-induced inhibition of IK (V). Addition of
guanosine-5'-O-(3-thiophosphate) in the pipette solution irreversibly sustained
the DTG-induced current whereas guanosine-5'-O-(2-thiodiphosphate) virtually
suppressed the response. Cholera toxin-pretreatment (1 microgram/ml; 18 hr)
abolished the inward current and the inhibition of IK (V) induced by sigma
ligands. In contrast, pretreatment with pertussis toxin (1 microgram/ml; 18 hr)
had no effect. Taken together, these data indicate that DTG and (+)-pentazocine
activate the electrical activity of cultured frog melanotrope cells by reducing
both a tonic K+ current and a voltage-dependent [IK (V)] K+ conductance through
the activation of a cholera toxin-sensitive G-protein.
PMID- 9655857
TI - Citalopram enhances the activity of chloroquine in resistant plasmodium in vitro
and in vivo.
AB - Citalopram, is an extremely potent inhibitor of neuronal serotonin reuptake. It
is structurally unrelated to other antidepressants, but it contains the chemical
features associated with reversal of drug resistance and exhibits minimal
cardiotoxic side effects and fewer of the anticholinergic and adrenolytic side
effects associated with other psychotropic agents. Sensitivity tests to
citalopram alone and in combination with chloroquine were performed against
chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum
and Plasmodium chabaudi. Citalopram alone showed intrinsic activity against the
chloroquine-resistant strains of P. falciparum (IC50 = 1.51 +/- .6 microM) but
only limited activity against the chloroquine-sensitive strain (IC50 = 33.27 +/-
5.87 microM) and no activity in vivo. The interaction of chloroquine and
citalopram in vitro resulted in a synergistic response in the chloroquine
resistant strain but there was no interaction between the drugs in the
chloroquine-sensitive strain--a pattern found with other reversal agents.
Citalopram enhanced chloroquine susceptibility in both strains of P. chabaudi,
however, the potentiating effect was seen at lower doses in the chloroquine
resistant strain. The results of this study suggest that citalopram may have
potential as a chemosensitizer in Plasmodium infections on the basis of the low
toxicity of citalopram at concentrations potentiating chloroquine activity both
in vitro and in vivo.
PMID- 9655858
TI - A new sodium/hydrogen exchange inhibitor, EMD 85131, limits infarct size in dogs
when administered before or after coronary artery occlusion.
AB - Administration of inhibitors of the Na+/H+ exchanger (NHE) have been shown to
produce cardioprotective effects in a number of animal models of ischemia
reperfusion injury; however, controversy still exists as to the efficacy of these
agents when administered just before reperfusion. To address this question, the
efficacy of several doses of a new selective NHE-1 isoform inhibitor (IC50 for
inhibition of 22Na uptake in NHE-1 expressing mouse fibroblast cells = 10.4 +/-
1.0 nM), EMD 85131 (2-methyl-5-methylsulfonyl-1-(1-pyrrollyl)-benzoyl-guanidine),
was tested in a canine infarct model in which the left anterior descending
coronary artery was occluded for 60 min followed by 3 hr of reperfusion. EMD
85131 (0.75 or 3.0 mg/kg) was infused for 15 min before left anterior descending
occlusion or 15 min before reperfusion. Infarct size was determined by use of the
triphenyltetrazolium chloride histochemical stain and was expressed as a percent
of the area at risk. EMD 85131 (0.75 or 3.0 mg/kg) administered before left
anterior descending occlusion produced a marked (*P < .05) and dose-related
reduction in IS/AAR (24.3 +/- 3.6, control; 9.3 +/- 3.4%, EMD 0.75; 6.4 +/- 2.3%,
EMD 3.0). These two doses of EMD also produced significant (*P < .05) reductions
in infarct size/area at risk (12.2 +/- 2.1%, EMD 0.75; 13.0 +/- 2.9%, EMD 3.0)
when administered 15 min before reperfusion. These results suggest that selective
NHE-1 inhibitors are able to markedly reduce infarct size when given before or
during ischemia and also suggest that these compounds may have clinical utility
when administered after the initiation of an ischemic insult.
PMID- 9655859
TI - Synthesis and characterization of diazomethylarachidonyl ketone: an irreversible
inhibitor of N-arachidonylethanolamine amidohydrolase.
AB - N-Arachidonylethanolamine (AEA), a putative endogenous agonist of neuronal (CB1)
cannabinoid receptors, is a substrate for N-arachidonylethanolamine
amidohydrolase (AEA amidohydrolase), a serine amidase present in cell membranes.
Following a strategy that has been used to develop inhibitors that covalently
bind to the active site of serine peptidases, diazomethyl arachidonyl ketone
(DAK) was synthesized and its effects on AEA amidohydrolase were determined. DAK
inhibits the hydrolysis of AEA by rat brain membranes with an IC50 value of 0.5
microM. At low concentrations, DAK reduces the Vmax and increases the K(m) of the
enzyme for its substrate AEA, which suggests that it is both a competitive and
noncompetitive inhibitor. At higher concentrations, DAK inhibition is completely
noncompetitive. DAK inhibition of membrane-associated AEA amidohydrolase is
irreversible because hydrolytic activity is not restored with extensive washing
or dialysis of the membranes. Furthermore, DAK inhibition is not reversible by
anion exchange chromatography of the subsequently solubilized enzyme. In
contrast, DAK inhibition of detergent-solubilized enzyme exhibits competitive
kinetics and is reversible upon ion exchange chromatography. Exposure of C6
glioma cells to DAK results in concentration-related inhibition of AEA
amidohydrolase activity in cellular membranes with an IC50 value of 0.3 microM.
In summary, these studies demonstrate that DAK is an irreversible inhibitor of
AEA amidohydrolase in its native membrane and provides a useful tool with which
to study the role of AEA amidohydrolase in the termination of action of AEA.
PMID- 9655860
TI - Species- and gender-related differences in cyclosporine/prednisolone/sirolimus
interactions in whole blood lymphocyte proliferation assays.
AB - Cyclosporin A (CyA), prednisolone (Pred) and sirolimus (Sir) inhibit lymphocyte
proliferation at the cytokine transcription (CyA and Pred) or signal transduction
(Sir) levels. Their double and triple interactions were studied on lectin-induced
proliferation of whole blood lymphocytes (WBLP) from male and female humans,
rabbits and rats. Isobols along with the Universal Response Surface Approach were
used to describe and quantify the nature and intensity of drug interactions by
determining alpha values. CyA was always less potent than Pred and Sir while
these two compounds were relatively equipotent. Species-related differences were
observed with single drugs. Rabbit WBLP were resistant to Pred action (Imax =
67%) and rats were more sensitive to Pred (IC50 = 9.1 nM in females) and Sir (2.8
nM) actions than humans (32 and 55 nM). Gender differences were observed but were
not consistent across species. All double-drug combinations were synergistic, and
combinations containing Pred were 10 to 100 times more synergistic in rabbits
(alpha Pred/Sir = 213 and alpha CyA/Pred = 147 in males) than in rats (12 and
2.1) or humans (3.7 and 5.7) in relation to the lower efficacy of Pred. Double
combination alpha values were able to describe CyA/Pred/Sir triple combination
effects. These studies indicate that CyA, Pred and Sir act and synergistically
interact in vitro in species- and gender-dependent fashions. Adrenalectomized
rats better resemble humans in these responses. WBLP are useful in various
species in determining immunosuppressive drug action and interactions.
PMID- 9655861
TI - Influence of lubeluzole on voltage-sensitive Ca++ channels in isolated rat
neurons.
AB - Lubeluzole is neuroprotective in a photochemical stroke model, whereas the (R)
enantiomer of the same molecule is not [De Ryck M, Keersmaekers R, Duytschaever
H, Claes C, Clincke G, Janssen M and Van Reet G (1996) J Pharmacol Exp Ther
279:748-758]. We investigated the effects of lubeluzole and the (R)-enantiomer on
voltage-sensitive Ca++ channels of isolated rat dorsal root ganglion cells, using
whole-cell voltage-clamp, with Ba++ as the charge carrier. Both compounds blocked
the low-voltage-activated Ba++ current (iLVA or T current) with an IC50 value of
1.2 microM. Lubeluzole and the (R)-enantiomer also blocked the high-voltage
activated calcium channel current (iHVA), with IC50 values of 2.6 and 3.5 microM,
respectively, and accelerated the apparent inactivation of iHVA. This
acceleration was more pronounced with lubeluzole than with the (R)-enantiomer at
3 and 10 microM. Both compounds produced a clear tonic block of iLVA and iHVA,
even in the absence of previous stimulation. Lubeluzole and the (R)-enantiomer
induced a negative shift of the inactivation curve of iLVA and showed down the
recovery from inactivation. This resulted in a stronger inhibition of iLVA at
more depolarized conditioning potentials and higher stimulation frequencies. The
block of iHVA was voltage and frequency dependent. Lubeluzole and the (R)
enantiomer also blocked iHVA in isolated rat superior cervical ganglion cells and
cerebellar Purkinje cells. The Ca++ channel-blocking properties of lubeluzole may
contribute to its neuroprotective effect. However, the small difference between
the two enantiomers in inhibition of Ca++ channel currents does not explain the
stereospecificity of the neuroprotective properties of lubeluzole in vitro and in
vivo.
PMID- 9655862
TI - Nitric oxide-releasing oxatriazole derivatives inhibit human lymphocyte
proliferation by a cyclic GMP-independent mechanism.
AB - Two novel nitric oxide (NO)-releasing oxatriazole derivatives, GEA 3162 and GEA
3175, and an earlier known NO donor, S-nitroso-N-acetylpenicillamine (SNAP),
inhibited cell proliferation and enhanced cGMP production in a concentration
dependent manner in human lymphocytes activated by lectin mitogen concanavalin A
(ConA). The possible mediator role of cGMP in the antiproliferative action of NO
donors was tested by pharmacological means. An inhibitor of guanylate cyclase, 1H
[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, inhibited NO donor-induced cGMP
production, whereas the antiproliferative action of NO donors remained unaltered.
Phosphodiesterase inhibitors zaprinast and 3-isobutyl-1-methylxanthine
potentiated and prolonged NO donor-induced increase in the concentrations of cGMP
but did not enhance the antiproliferative action of NO donors. In addition, two
analogs of cGMP, 8-bromo-cGMP and a more cell-permeable compound, 8-p
chlorophenylthio-cGMP, did not inhibit ConA-stimulated lymphocyte proliferation
when used in concentrations of up to 300 microM. At millimolar concentrations, 8
bromo-cGMP had a moderate inhibitory action. These results suggest that nitric
oxide-releasing oxatriazole derivatives inhibit proliferative responses in human
lymphocytes by a cGMP-independent manner.
PMID- 9655863
TI - Effects of local anesthetics on acetylcholine-induced desensitization of guinea
pig ileal longitudinal muscle.
AB - We investigated which of the major actions of local anesthetics (i.e., inhibition
of phospholipase A2, interaction with Ca++ channels or blockade of receptor) was
responsible for the inhibition of acetylcholine-induced desensitization in guinea
pig ileal longitudinal muscle. Desensitization was inhibited by amine local
anesthetics and related compounds in the order of potency quinacrine >
chloroquine > tetracaine > procaine. Potent phospholipase A2 inhibitors,
manoalide (1 microM) and p-bromophenacyl bromide (5 microM) had no effect on
desensitization. The rank order of interaction of local anesthetics with Ca++
channels did not agree with the potency order of inhibition of desensitization.
These data indicated that local anesthetics did not inhibit desensitization
through their inhibition of phospholipase A2 or their interaction with Ca++
channels. Quinacrine, chloroquine, tetracaine and procaine inhibited [3H]N
methylscopolamine binding to solubilized membrane with pKi values of 7.03 +/-
0.10, 6.59 +/- 0.02, 5.40 +/- 0.10 and 5.03 +/- 0.04 and reduced receptor
occupancy by agonist from 99.0% (without inhibitor) to 96.8%, 95.1%, 89.4% and
49.8%, respectively, under the conditions where each drug induced half-maximum
inhibition of desensitization, indicating that they (except for procaine) did not
effectively block muscarinic receptors. However, the combined dose-ratio test
showed that some of these drugs (quinacrine and chloroquine) interacted
noncompetitively at muscarinic receptors. Therefore, these drugs could have bound
to an allosteric site on the receptor, modified agonist-receptor interaction and
thus inhibited the pathway specific to the desensitization process.
PMID- 9655864
TI - Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia
in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus
monkeys.
AB - The effects of dopamine receptor agonists on urinary bladder function were
evaluated in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
lesioned parkinsonian cynomolgus monkeys to investigate the therapeutic efficacy
in the treatment of urinary symptoms in Parkinson's disease. Under ketamine
anesthesia, cystometrograms exhibited significant reduction in the volume
threshold for the micturition reflex in MPTP-lesioned parkinsonian monkeys when
compared with those of normal monkeys. The selective dopamine D2 receptor agonist
bromocriptine significantly reduced the bladder volume threshold for the
micturition reflex by 25 to 30% in both normal and MPTP-lesioned animals. The
nonselective D1/D2 receptor agonist pergolide significantly reduced the bladder
volume threshold by 22% in normal monkeys, but increased the volume threshold by
50% in MPTP-lesioned parkinsonian monkeys. Another D1/D2 agonist (5R,8R,10R)-6
methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline maleate (BAM-1110) also increased
the bladder volume threshold (by 80%) in parkinsonian monkeys without significant
effects on the micturition reflex in normal monkeys. The reduction in the volume
threshold by bromocriptine in both normal and MPTP-treated groups and by
pergolide in normal monkeys was suppressed by pretreatment with the selective D2
antagonist sulpiride, whereas the increment in the volume threshold by pergolide
and BAM-1110 in parkinsonian monkeys was antagonized by pretreatment with the
selective D1 antagonist SCH 23390, but not by sulpiride. These findings suggest
that concurrent activation of D1/D2 receptors, rather than selective stimulation
of D2 receptors, might be beneficial for treating urinary symptoms caused by
detrusor hyperreflexia in Parkinson's disease.
PMID- 9655865
TI - M2 muscarinic receptors inhibit forskolin- but not isoproterenol-mediated
relaxation in bovine tracheal smooth muscle.
AB - The ability of the M2 muscarinic receptor to inhibit the relaxant effects of
forskolin and isoproterenol was investigated in bovine trachea. In most
experiments, we measured contractile responses to oxotremorine-M in smooth muscle
isolated from bovine trachea in which a majority of M3 receptors were inactivated
by treatment with N-(2-chloroethyl)-4-piperidinyl diphenylacetate. In the
presence of histamine (20 microM), the histamine H2 antagonist cimetidine (10
microM) and forskolin (4 microM), responses to oxotremorine-M were antagonized by
[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H
pyrido[2,3b][1,4]benzodiazepine-6-one (1 microM) in a manner consistent with
contractions mediated predominantly by M2 receptors. When similar experiments
were conducted in the presence of isoproterenol (0.1 microM) instead of
forskolin, contractions were antagonized in a manner consistent with an M3
receptor-mediated response. In similar experiments, we measured the relaxant
potency of isoproterenol and forskolin against histamine-induced contractions in
N-(2-chloroethyl)-4-piperidinyl diphenylacetate-treated trachea. By itself,
oxotremorine-M (7.5 nM) had no contractile effect; however, it caused a
substantial reduction in the relaxant potency of forskolin although having little
effect on that of isoproterenol. These experiments establish that M2 receptors
inhibit the relaxant effects of forskolin, but not isoproterenol. In untreated
tissues, the relaxant responses to isoproterenol and forskolin were 10.8- and
14.2-fold more potent, respectively, against histamine than against oxotremorine
M-induced contractions of equal magnitude. Similarly, the maximal stimulation of
cAMP accumulation elicited by isoproterenol and forskolin was inhibited 58 and
62%, respectively, in the presence of oxotremorine-M (80 nM) compared to that
measured in the presence of histamine (20 microM). Analysis of the data indicated
that isoproterenol elicited relaxation at concentrations well beyond those that
stimulated maximal levels of cAMP accumulation. Our results indicate that part of
the relaxant response to isoproterenol is mediated through a non-cAMP-dependent
mechanism, and that this mechanism is largely unopposed by the M2 receptor.
PMID- 9655866
TI - Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role
of protein tyrosine phosphorylation and calcineurin.
AB - In the present study, rundown of gamma-aminobutyric acid (GABA)-activated Cl-
channels was studied in recombinant GABAA receptors stably expressed in human
embryonic kidney cells (HEK 293), with conventional whole-cell and amphotericin B
perforated patch recording. When [ATP]i was lowered to 1 mM and resting [Ca++]i
was buffered to a relatively high level, the response of alpha 3 beta 2 gamma 2
GABAA receptors to relatively low [GABA] (up to 50 microM) did not show rundown
in the whole-cell configuration. However, high [GABA] (greater than 200 microM)
induced significant rundown, which was observed by decreases in both the maximum
GABA-induced current and GABA EC50. Rundown was prevented completely with a
solution containing 4 mM Mg(++)-ATP and low resting [Ca++]i, or during perforated
patch recording. The magnitude of rundown was comparable in alpha 1 beta 2 gamma
2 and beta 2 gamma 2 receptors. Neither stimulation nor inhibition of protein
kinase A or protein kinase C had a significant effect on rundown. However, sodium
metavanadate, an inhibitor of protein tyrosine phosphatase, significantly reduced
rundown. In addition, inhibition of protein tyrosine kinase activity by either
genistein or lavendustin A induced rundown of the GABA response. Inhibition of
the Ca++/calmodulin-dependent phosphatase calcineurin with fenvalerate also
prevented rundown of the response to GABA. Our results demonstrate that rundown
of GABAA receptor function is concentration-dependent, due to depletion of ATP
and/or unbuffered [Ca++]i, and does not depend on the presence or subtype of the
alpha subunit. We propose that protein phosphorylation at a tyrosine kinase
dependent site, and a distinct unidentified site, which is dephosphorylated by
calcineurin, maintains the function of GABAA receptors.
PMID- 9655867
TI - Alterations in 8-hydroxy-2-(dipropylamino)tetralin-induced neuroendocrine
responses after 5,7-dihydroxytryptamine-induced denervation of serotonergic
neurons.
AB - In the present study, we examined denervation-induced changes in the sensitivity
of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect
to changes in the dose-dependent elevation in plasma hormones
[adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin,
prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2
(dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular
(i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT)
or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing
doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of
5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93%
reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No
changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and
vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The
dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone
and prolactin levels were shifted to the left in rats treated with 5,7-DHT,
whereas no significant difference in the ACTH dose-response curve was observed
between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the
maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7
DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this
phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or
vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%)
in plasma renin concentration but not in vasopressin levels in rats that received
i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5
HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic
serotonergic nerve terminals produces supersensitivity of some neuroendocrine
responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5
HT1A receptors.
PMID- 9655868
TI - Provisional mapping of quantitative trait loci for chronic ethanol withdrawal
severity in BXD recombinant inbred mice.
AB - Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI)
strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for
72 hr. Mice were selected such that each strain averaged 1.34 to 1.59 mg of
EtOH/ml of blood on withdrawal. Control groups and EtOH-exposed groups were
tested hourly for handling-induced convulsions (HIC) for 10 hr and at hr 24 and
25. Strain withdrawal severity was indexed as the area under the 25-hr HIC curve
for the EtOH group minus that strain's equivalent value for the control group.
Genome-wide quantitative trait locus (QTL) analyses correlating strain means with
allelic status at > 1500 markers identified 10 chromosomal regions at P < .01.
These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2
QTLs), 10, 12, 13, 15 and 18. Multiple regression analysis using the four most
influential QTLs revealed that these loci controlled 86% of the genetic variance.
A QTL mapped to distal chromosome 1 (P < .001) is in the same region as one
previously definitively mapped for acute alcohol withdrawal, as well as one
mapped for acute pentobarbital withdrawal. Several of the QTLs map near potential
candidate genes. These provisional linkages will now be confirmed or rejected
using additional genetically segregating populations.
PMID- 9655869
TI - Effects of full D1 dopamine receptor agonists on firing rates in the globus
pallidus and substantia nigra pars compacta in vivo: tests for D1 receptor
selectivity and comparisons to the partial agonist SKF 38393.
AB - Many studies have used the D1 agonist SKF 38393 to characterize D1 receptor
influences on firing rates in basal ganglia nuclei in vivo. However, SKF 38393 is
a partial agonist and so may not be ideal for delineating D1 receptor effects.
This study characterizes the effects of four full D1 agonists, SKF 82958 (chloro
APB), SKF 81297 (6-chloro-PB), dihydrexidine and A-77636, on the firing rates of
midbrain dopamine and globus pallidus neurons. Recordings were done in fully
anesthetized or paralyzed, locally anesthetized rats, and drugs were given
systemically intravenously. Dihydrexidine, SKF 81297 and A-77636 were free of
rate effects on midbrain dopamine neurons (up to 10.2 mg/kg) and also did not
antagonize the inhibitory effects of quinpirole. In contrast, SKF 82958 strongly
inhibited dopamine cells through activation of D2 autoreceptors (ED50 = 0.70
mg/kg). Of these drugs, SKF 82958 also was the only one to increase pallidal unit
firing rates when given alone (at 5.0 but not 1.0 mg/kg); the other compounds
appeared to be selective for postsynaptic D1 receptors. The results suggest that
SKF 82958 may be more properly classified as a mixed D1/D2 agonist. In addition,
all four agonists strongly potentiated the pallidal response to quinpirole,
demonstrating a D1 receptor potentiation of D2 receptor effects. The results
support the role of D1 receptors in the midbrain and globus pallidus as
previously characterized with SKF 38393. The similar actions of partial and full
D1 agonists in these systems support evidence for a D1 receptor reserve and
possibly an effector system other than adenylate cyclase.
PMID- 9655870
TI - Stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate binding by endogenous
opioids acting at a cloned mu receptor.
AB - The ability of endogenous opioids to activate G proteins was measured in
membranes from C6 rat glioma cells stably expressing a cloned rat mu receptor.
Peptides representing each of the three known families of endogenous opioids
(enkephalins, endorphins and dynorphins) were studied, as well as two recently
discovered endogenous opioids, endomorphin-1 and -2, which are thought to
represent a fourth family of endogenous opioid peptides. Stimulation of guanosine
5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) binding to membranes was used
as a measure of G protein activation. It was possible to differentiate high
efficacy compounds such as Tyr-D-Ala-Gly-(Me)Phe-Gly-ol from lower-efficacy
agonists such as morphine or meperidine. Met- and leu-enkephalin, beta endorphin
and dynorphin A were all found to have high efficacy at the mu receptor, as were
the peptide fragments beta endorphin-1(1-27) and dynorphin A-(1-13). Endomorphin
1 and -2 were found to be partial agonists, capable of both stimulating [35S]GTP
gamma S binding and antagonizing the stimulation produced by the higher-efficacy
agonist Tyr-D-Ala-Gly-(Me)Phe-Gly-ol. Binding affinities for the opioid agonists
at the cloned mu receptor were measured by the displacement of radiolabeled
antagonist. It was found that the Ki values closely matched the EC50 values for
[35S]GTP gamma S binding stimulation, indicating that a large receptor reserve
does not exist for the complete activation of G proteins in this system.
PMID- 9655871
TI - A role for tryptase in the activation of human mast cells: modulation of
histamine release by tryptase and inhibitors of tryptase.
AB - Tryptase, the most abundant protein product of human mast cells is emerging as an
important mediator and target for therapeutic intervention in allergic disease.
We have investigated the potential of tryptase and inhibitors of tryptase to
modulate histamine release from human mast cells. Addition of purified human
tryptase in concentrations ranging from 1 to 100 mU/ml stimulated a concentration
dependent release of histamine from cells dispersed from tonsil, although not
from skin tissue. The reaction dependent on an intact catalytic site being
inhibited by heat inactivation of the enzyme, or by preincubating with the
tryptase inhibitors APC366 or leupeptin or the tryptic substrate N-benzoyl-DL
arginine-p-nitroanilide (BAPNA). Tryptase-induced histamine release took
approximately 6 min to reach completion, appeared to require exogenous calcium
and magnesium, and on the basis of inhibition by antimycin A and 2-deoxy-D
glucose, seemed to be a noncytotoxic process. Pre-incubation of cells with
tryptase at concentrations that were suboptimal for histamine release had little
effect on their responsiveness to anti-immunoglobulin (Ig) E or to calcium
ionophore A23187, but at higher concentrations their subsequent activation was
inhibited. APC366 significantly inhibited histamine release induced by anti-IgE
or calcium ionophore from both tonsil and skin cells, with up to 90% inhibition
being observed at a concentration of 100 microM with skin. IgE-dependent
histamine release was inhibited also by leupeptin, benzamidine and BAPNA.
Tryptase may act as an amplification signal for mast cell activation, and this
could account at least partly for the potent mast cell stabilizing properties of
tryptase inhibitors.
PMID- 9655872
TI - Effects of nitric oxide on adenylyl cyclase stimulation in N18TG2 neuroblastoma
cells.
AB - The addition of nitric oxide (NO), in the form of either donor compounds or
nitric oxide gas, inhibits hormone-stimulated cAMP accumulation in N18TG2 cells.
Hormone receptors and Gs are not targets of NO because forskolin-stimulated cAMP
accumulation is also inhibited. The inhibitory effect of NO is not altered by
pretreatment of cells with pertussis toxin, indicating that Gi is not mediating
the effect of NO. cAMP accumulation in these cells is not altered by cell
incubation with Ca++ ionophore or calmidazolium, indicating that calmodulin is
not the target for NO. Experiments also rule out changes in phosphodiesterase or
cGMP as mediators of the effect of NO. Cell incubation with superoxide dismutase
in the presence or absence of catalase indicate that nitric oxide is the reactive
species. The inhibitory action of nitric oxide is readily reversed, allowing full
recovery of hormone and forskolin stimulation within 20 min of incubation in the
absence of nitric oxide. The sum of the data indicate that NO targets either the
adenylyl cyclase itself, or a regulatory component distinct from G proteins or
calmodulin, to inhibit activation of the enzyme.
PMID- 9655873
TI - Regulation of organic cation transport in IHKE-1 and LLC-PK1 cells. Fluorometric
studies with 4-(4-dimethylaminostyryl)-N-methylpyridinium.
AB - The regulation of transport of the fluorescent organic cation 4-(4
dimethylaminostyryl)-N-methylpyridinium (ASP+) by renal proximal tubular organic
cation transport was studied in IHKE-1 and LLC-PK1 cells with a recently
established fluorometric technique (Stachon et al., 1996, 1997). Stimulation of
Ca++/diacylglycerol-dependent protein kinase by 1,2-dioctanoyl glycerol (DOG;
0.01-1 mumol/l, n = 7), ATP (0.1 mmol/l, n = 9), oxytocin (0.1 mumol/l, n = 6)
and bradykinin (1 mumol/l, n = 7) resulted in an increase of ASP+ accumulation in
IHKE-1 cells by 35 +/- 9% (DOG), 65 +/- 30% (ATP), 66 +/- 14% (bradykinin) and 70
+/- 20% (oxytocin) as compared with basal conditions, whereas ASP+ accumulation
was slightly reduced in LLC-PK1 cells after stimulation with DOG (1 mumol/l, -20
+/- 7%, n = 10) and angiotensin II (0.1 nmol/l, -20 +/- 5%, n = 6). ASP+
accumulation in IHKE-1 cells also was increased by 0.5 mumol/l (20 +/- 8%, n = 8)
and 1 mumol/l forskolin (35 +/- 13%, n = 19), and by 8-bromo-cAMP (1 mumol/l, 125
+/- 25%, n = 9), both activators of the cAMP-dependent protein kinase (PKA).
Activation of the cGMP-dependent protein kinase (PKG) by human atrial natriuretic
peptide (10 nmol/l, n = 10) or 8-bromo-cGMP (0.1 mmol/l, n = 12) resulted in an
increase of 35 +/- 5% and 28 +/- 6%, respectively. Activation of PKA and PKG had
no influence on ASP+ transport in LLC-PK1 cells. Regulation of ASP+ uptake by
these two cell lines may be caused by direct phosphorylation of the organic
cation transporters involved or by regulation of trafficking of the transporters
to the membrane. Differences in the organic cation transporter isoforms or
alternatively, in the trafficking may contribute to the distinct regulation of
ASP+ transport in IHKE-1 and LLC-PK1 cells.
PMID- 9655874
TI - alpha 5 Subunit alters desensitization, pharmacology, Ca++ permeability and Ca++
modulation of human neuronal alpha 3 nicotinic receptors.
AB - Functional effects of human alpha 5 nicotinic ACh receptor (AChR) subunits
coassembled with alpha 3 and beta 2 or with alpha 3 and beta 4 subunits, were
investigated in Xenopus oocytes. The presence of alpha 5 subunits altered some
properties of both alpha 3 AChRs and differentially altered other properties of
alpha 3 beta 2 AChRs vs. alpha 3 beta 4 AChRs. alpha 5 subunits increased
desensitization and Ca++ permeability of all alpha 3 AChRs. The Ca++
permeabilities of both alpha 3 beta 2 alpha 5 and alpha 3 beta 4 alpha 5 AChRs
were comparable to that of alpha 7 AChRs. As we have shown previously, alpha 5
subunits increased the ACh sensitivity of alpha 3 beta 2 AChRs 50-fold but had
little effect on alpha 3 beta 4 AChRs. alpha 5 caused only subtle changes in the
activation potencies of alpha 3 AChRs for nicotine, cytisine and 1,1-dimethyl-4
plenylpiperazinium (DMPP). However, alpha 5 increased the efficacies of nicotine
and DMPP on alpha 3 beta 2 AChRs but decreased them on alpha 3 beta 4 AChRs.
Immunoisolation of cloned human AChRs expressed in oocytes showed that alpha 5
efficiently coassembled with alpha 3 plus beta 2 and/or beta 4 subunits. As
expected, human AChRs immunoisolated from SH-SY5Y neuroblastoma cells showed that
AChRs containing alpha 3 and probably alpha 5 subunits were present, but alpha 4
AChRs were not. In brain, by contrast, alpha 4 beta 2 AChRs were shown to
predominate over alpha 3 AChRs. Some of the brain alpha 4 beta 2 AChRs were found
to contain alpha 5 subunits.
PMID- 9655875
TI - Heterologous expression of various P-glycoproteins in polarized epithelial cells
induces directional transport of small (type 1) and bulky (type 2) cationic
drugs.
AB - We recently showed that absence of mdr1-type P-glycoprotein (P-gp) in mice
resulted in profoundly reduced hepatic and intestinal clearance of type 1 and
type 2 cationic drugs compared with that in wild-type mice. These data strongly
support the concept that mdr1-type P-gps are involved in the disposition of
cationic amphiphilic drugs from the body. We tested the hypothesis that mdr1-type
P-gps are involved in the transmembrane transport of organic cations in
epithelial cells expressing various drug-transporting P-gps. Therefore,
transepithelial transport of the P-gp substrate vinblastine, the steroidal (type
2) cation vecuronium, the relatively small (type 1) cationic compound
azidoprocainamide methoiodide and the aliphatic cation tri-n-butylmethylammonium
were measured. Apical expression of the mdr1a, mdr1b or MDR1 gene in confluently
grown polarized transformed LLC-PK1 cells resulted in highly enhanced apical
directed secretion of all the drugs tested compared with controls. The vectorial
transport of tri-n-butylmethylammonium in the apical direction in the P-gp
(over)expressing cells could be inhibited by vinblastine. The present
observations show that apical secretion of type 1 as well as of type 2 organic
cations is enhanced significantly in the presence of apical expressed mdr1-type P
gp. These findings provide evidence for the involvement of drug-transporting P-gp
in transmembrane transport of various organic cations, including relatively small
molecular weight aromatic and aliphatic compounds.
PMID- 9655876
TI - Modulation of intestinal estrogen receptor by ovariectomy, estrogen and growth
hormone.
AB - Ovarian hormone deficiency decreases and estrogen (E2) and growth hormone (GH)
administrations increase intestinal absorption of calcium (Ca++). However, the
underlying mechanisms are uncertain. To examine whether alterations in the
binding characteristics of intestinal estrogen receptors (ERs) are involved, we
developed and validated methods for simultaneous measurement of intestinal ERs in
cytosolic and nuclear fractions and applied these techniques to four groups of
female rats: sham-operated, ovariectomized (Ovx), Ovx + 5 micrograms E2/kg
b.wt./day and Ovx + 8 mg GH/kg. b.wt./day. All animals were killed on day 21, and
mucosal cells harvested from the duodenum for ER determination. The cytosolic and
nuclear ERs were 117.2 +/- 2.7 fmol/mg protein and 64.9 +/- 1.2 fmol/mg DNA,
respectively, in sham-operated rats and decreased by 16.1% and 17.0% to 98.4 +/-
1.7 fmol/mg protein and 53.8 +/- 1.3 fmol/mg DNA, respectively in Ovx rats (P <
.001). E2 therapy prevented completely the decrease in cytosolic and nuclear ERs
that occurred in Ovx rat (126.1 +/- 2.9 fmol/mg protein and 68.0 +/- 3.0 fmol/mg
DNA, respectively, in the E2-treated group). Similarly, GH administration
prevented the decrease in cytosolic and nuclear ERs that resulted from
ovariectomy (119.2 +/- 3.2 fmol/mg protein and 63.4 +/- 1.3 fmol/mg DNA,
respectively, in the GH-treated group). The Kd of nuclear ER-ligand complex was
2.0 +/- 0.03 nM in sham-operated rats and was slightly modulated by Ovx, E2 and
GH (3.3 +/- 0.02, 2.33 +/- 0.09 and 2.23 +/- 0.04 nM, respectively, P < .001),
but the Kd of cytosolic ER-ligand complex was not altered by Ovx, E2 or GH. Our
findings indicate that E2 deficiency down-regulates, whereas E2 and GH
administrations up-regulate intestinal ERs and prevent ovariectomy-induced
decrease in receptor binding affinity. We conclude that E2 deficiency, E2 and GH
may modulate intestinal Ca++ absorption, in part, by altering the abundance and
binding characteristics of intestinal ERs.
PMID- 9655877
TI - Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non
N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
AB - Previous studies have shown that toluene, which is commonly abused, depresses
neuronal activity and causes behavioral effects in both animals and man similar
to those observed for ethanol. In this study, the oocyte expression system was
used to test the hypothesis that toluene, like ethanol, inhibits the function of
ionotropic glutamate receptors. Oocytes were injected with mRNA for specific N
methyl-D-aspartate (NMDA) or non-NMDA subunits and currents were recorded using
conventional two-electrode voltage clamp. To enhance the low water solubility of
toluene, drug solutions were prepared by mixing toluene with alkamuls
(ethoxylated castor oil) at a 1:1 ratio (v:v) and diluting this mixture to the
appropriate concentration with barium-containing normal frog Ringer solution.
Alkamuls, up to 0.1%, had no significant effects on membrane leak currents or on
NMDA-induced currents. Toluene, up to approximately 9 mM, had only minor effects
on membrane leak currents but dose-dependently inhibited NMDA-mediated currents
in oocytes. The inhibition of NMDA receptor currents by toluene was rapid,
reversible and the potency for toluene's effects was subunit dependent. The
NR1/2B subunit combination was the most sensitive with an IC50 value for toluene
induced inhibition of 0.17 mM. The NR1/2A and NR1/2C receptors were 6- and 12
fold less sensitive with IC50 values of 1.4 and 2.1 mM, respectively. In
contrast, toluene up to approximately 9 mM did not inhibit kainate-induced
currents in oocytes expressing GluR1, GluR1(+)R2 or GluR6 subunits. These results
suggest that some of the effects of toluene on neuronal activity and behavior may
be mediated by inhibition of NMDA receptors.
PMID- 9655878
TI - Parathyroid hormone (1-34) increased total body bone mass in aged female rats.
AB - Daily subcutaneous administration of bovine parathyroid hormone (PTH)(1-34)
stimulates bone formation and increases bone mass in rat tibiae, femora and
lumbar spine. However, the effects of PTH on the whole body bone mineral content
and density determined by dual energy x-ray absortiometry (DEXA) have not been
previously reported in rats. Eighteen-month-old intact female rats were
subcutaneously injected daily with 0, 40, 80 or 160 micrograms/kg/day of bovine
PTH (1-34) for either 15 or 60 days. Whole body DEXA was performed at 1 day
before autopsy, and bone area, bone mineral content (BMC) and bone mineral
density (BMD) of the total body were determined. Total femoral, tibial and lumbar
spine BMD was also determined ex vivo. Cancellous bone histomorphometry was
performed on sections of double-labeled proximal tibial metaphyses. Whole body
bone mineral content and density were significantly increased by 60 days, but not
by 15 days, of PTH treatment at all dose groups compared with vehicle controls.
Lumbar vertebral and total femoral BMD was significantly increased at all doses
of PTH by 15 days of administration and further increased by 60 days. All doses
of PTH increased trabecular bone area in proximal tibial metaphyses by 15 days
and further increased by 60 days. All doses of PTH increased trabecular bone area
in proximal tibial metaphyses by 15 days and further increased by 60 days. In
proximal tibial cancellous bone, dose-dependent increases in percent labeled
perimeter, mineral apposition rate and bone formation rate-bone volume referent
were found between 40 and 160 micrograms/kg of PTH treatment by 15 days, and no
further increases were found by 60 days. Our results showed that in aged female
rats, bovine PTH(1-34) increased bone formation and total body bone mass.
PMID- 9655879
TI - Homologous desensitization of the D1A dopamine receptor: efficacy in causing
desensitization dissociates from both receptor occupancy and functional potency.
AB - The role of drug efficacy in agonist-induced desensitization was studied in C-6
glioma cells transfected with the monkey dopamine D1A (mD1A) receptor. Dopamine
pretreatment for 2 hr produced greater than 80% loss of responsiveness in the
stimulation of cAMP accumulation that was blocked by the D1 antagonist SCH23390.
A series of full and partial D1 agonists from structurally dissimilar classes
were then examined. Three full agonists (dihydrexidine, SKF82958, A77636)
desensitized the receptor to the same extent as dopamine, whereas two other full
agonists (dinapsoline and A68930) and all the partial agonists tested (SKF38393,
pergolide and d-lysergic acid diethylamide tartrate) produced only partial
desensitization (i.e., 50% that of dopamine). Whereas partial agonists (i.e.,
SKF38393, pergolide and d-lysergic acid diethylamide tartrate) caused no
alteration in ligand-accessible mD1A receptors, four of the full agonists
(dopamine, dihydrexidine, dinapsoline, A68930) caused a 30 to 40% reduction in
receptor number. One full agonist, A77636, caused nearly an 80% decrease in
receptor number, despite the fact that the degree of functional desensitization
was similar to the other full agonists. The desensitization of the D1 receptor
was homologous, not affecting beta-2 adrenergic receptors endogenous to C-6
cells. Neither incubation with cAMP analogs, nor inhibition of protein kinase A,
affected dopamine-induced desensitization, suggesting a cAMP-independent
mechanism in this cell line. Together, these data suggest that functional
desensitization of the mD1A receptor expressed in C-6 glioma cells is a cAMP
independent mechanism, cannot be predicted reliably from agonist efficacy for
stimulating adenylate cyclase and can occur in the absence of changes in receptor
number.
PMID- 9655880
TI - Functional characterization of an organic cation transporter (hOCT1) in a
transiently transfected human cell line (HeLa).
AB - Recently, a polyspecific organic cation transporter, hOCT1, was cloned from human
liver. To date, limited studies examining the functional characteristics of the
transporter have been performed. The purpose of the present study was to develop
a mammalian expression system for hOCT1 and to characterize the interactions of
various compounds with the cloned transporter. Lipofection was used to
transiently transfect the hOCT1 plasmid DNA in a human cell line, HeLa. We tested
the interaction of an array of organic cations and other compounds with hOCT1 by
determining Ki values in inhibiting 14C-tetraethylammonium (TEA) transport in the
transfected cells. Transient expression of hOCT1 activity was observed between 24
and 72 hr post-transfection, with maximal expression at approximately 40 hr. TEA
transport was temperature dependent and saturable with Vmax and K(m) values of
2.89 +/- 0.448 nmol/mg protein/30 min and 229 +/- 78.4 microM, respectively. 14C
TEA uptake in hOCT1 plasmid DNA-transfected HeLa cells was trans-stimulated by
unlabeled TEA and 1-methyl-4-phenyl-pyridinium. Organic cations, including
clonidine, quinine, quinidine and verapamil (0.1 mM), significantly inhibited 14C
TEA uptake, whereas the organic anion, p-aminohippuric acid (5 mM), did not. The
neutral compounds, corticosterone (Ki, 7.0 microM) and midazolam (Ki, 3.7 microM)
potently inhibited 14C-TEA uptake. The Ki values of several compounds in
interacting with hOCT1 differed substantially from the corresponding values for
the rat organic cation transporter, rOCT1, and the human kidney-specific organic
cation transporter, hOCT2, determined in previous studies. Transiently
transfected HeLa cells represent a useful tool in studying the interactions and
kinetics of organic cations and other xenobiotics with hOCT1 and in understanding
the molecular events involved in organic cation transport.
PMID- 9655881
TI - Behavioral effects of the delta-selective opioid agonist SNC80 and related
compounds in rhesus monkeys.
AB - The behavioral effects of the nonpeptidic delta opioid agonist SNC80 and a series
of related piperazinyl benzamides derived from the parent compound BW373U86 were
evaluated in rhesus monkeys. SNC80 (0.1-10 mg/kg) decreased response rates
maintained by food-reinforcement in a dose- and time-dependent manner, with
maximal effects occurring within 10 min of intramuscular injection. The potency
of SNC80 and five other piperazinyl benzamides in this assay of schedule
controlled responding correlated with their affinity at cloned human delta opioid
receptors but not with their affinity for cloned human mu receptors. Moreover,
the effects of SNC80 were selectively antagonized by the delta-selective
antagonist naltrindole (1.0 mg/kg), but not by the mu selective antagonist
quadazocine (0.1 mg/kg) or the kappa-selective antagonist norbinaltorphimine (3.2
mg/kg). These findings indicate that SNC80 functions as a systemically active,
delta-selective agonist with a rapid onset of action in rhesus monkeys. The
antinociceptive effects of SNC80 were examined in a warm-water tail-withdrawal
assay of thermal nociception. SNC80 (0.1-10 mg/kg) produced weak but replicable
antinociceptive effects that were antagonized by naltrindole (1.0 mg/kg). SNC80
antinociception was also dose-dependently antagonized by BW373U86 (0.56-1.0
mg/kg), which was inactive in this procedure. These findings suggest that SNC80
may have higher efficacy than BW373U86 at delta opioid receptors. Moreover, SNC80
at doses up to 32 mg/kg did not produce convulsions, which suggests that SNC80
may also be safer than BW373U86. The effects of SNC80 were also examined in
monkeys trained to discriminate cocaine (0.4 mg/kg i.m.) or self-administer
cocaine (0.032 mg/kg/injection,i.v.). In drug discrimination studies, SNC80 (0.1
10 mg/kg) produced a dose-dependent and naltrindole-reversible increase in
cocaine-appropriate responding, and complete substitution for cocaine was
observed in five of seven monkeys tested. However, SNC80 (1.0-100
micrograms/kg/injection) did not maintain responding in monkeys trained to self
administer cocaine. Thus, despite its ability to produce cocaine-like
discriminative stimulus effects, SNC80 may have relatively low abuse potential.
PMID- 9655882
TI - 3H-naloxone benzoylhydrazone binding in MOR-1-transfected Chinese hamster ovary
cells: evidence for G-protein-dependent antagonist binding.
AB - Naloxone benzoylhydrazone (NalBzoH) is a potent mu antagonist in vivo. In a cell
line stably transfected with MOR-1 (CHO/MOR-1), NalBzoH also was an antagonist
when examined in adenylyl cyclase studies. In binding studies, it displayed high
affinity for the mu receptor, confirming its earlier characterization in brain
membranes. In competition studies under equilibrium conditions, NalBzoH and
diprenorphine both retained their potency in the presence of the stable GTP
analog 5'-guanylylimidophosphate, consistent with their mu antagonist properties,
whereas the agonist DAMGO showed more than a 3-fold loss of affinity. The
dissociation of 3H-diprenorphine was monophasic. However, kinetic studies
revealed biphasic dissociations for both 3H-NalBzoH and 3H-DAMGO. The slow
component of 3H-NalBzoH dissociation, corresponding to the higher affinity state,
was dependent on coupling to G-proteins. It is selectively abolished by guanine
nucleotides, leaving only the rapid dissociation phase. Furthermore, the slow
dissociation component is eliminated by treatment of the cells with pertussis
toxin, but not cholera toxin. In conclusion, NalBzoH is an unusual opioid.
Functionally it is an antagonist, a classification consistent with its
equilibrium binding in the presence of guanine nucleotides. Yet, kinetic studies
reveal that it labels a G-protein coupled state of the receptor with high
affinity.
PMID- 9655883
TI - Characterization of G protein and phospholipase C-coupled agonist binding to the
Y1 neuropeptide Y receptor in rat brain: sensitivity to G protein activators and
inhibitors and to inhibitors of phospholipase C.
AB - Binding of a Y1-subtype-selective agonist of neuropeptide Y (NPY) receptor,
(Leu31,Pro34)human peptide YY (LP-PYY), to particulates from four rat brain areas
(parietal cortex area 1, piriform cortex, anterior hypothalamus and hippocampus)
showed a distinct response to LP-PYY and PYY, a uniformly low sensitivity to
ligands selective for the Y2, Y4 and Y5 NPY receptor subtypes and high
sensitivity to a Y1 site-selective antagonist, BIBP-3226. The Y1 binding was
sensitive to guanine nucleotide-binding protein (G protein) agonist and
antagonist nucleotides, with the rank order of guanosine 5'-O-(thiotriphosphate)
(GTP gamma S) > GTP > GDP > guanosine 5'-O-(thiodiphosphate). However, guanine
nucleotides did not affect about one third of the specific Y1 binding. Most of Y1
binding could be inhibited by a G protein nucleotide site/docking site receptor
mimic, mastoparan analog MAS-7. In all areas examined, the Y1 binding of LP-PYY
was little affected by up to 100 microM of the antagonists of K+, Na+ and Ca++
channels, protein kinase C, phospholipase A2, phospholipase D and
phosphatidylinositol 3-kinase, phospholipase substrate phospholipids, steroids or
detergents. However, the binding was potently inhibited by phospholipase C
inhibitors (especially the aminosteroid U-73122), which also dissociated the
bound Y1 ligand in steady-state conditions. U-73122 also displaced the Y1 binding
insensitive to GTP gamma S. Ligand association with the brain Y1 NPY receptor
thus strongly depends on activity of both G proteins and phospholipase C,
implying specific interactions of these transducers/effectors with the receptor
molecule in ligand binding. A portion of brain Y1 sites could be directly coupled
to phospholipase(s) C.
PMID- 9655884
TI - Comparison of tamoxifen effects on the actions of triiodothyronine or growth
hormone in the ovariectomized-hypothyroid rat.
AB - Recent studies have suggested that a subset of estrogen responses arise via
modulation of triiodothyronine (T3) actions, and depend on T3 for expression:
other estrogen responses are not T3-dependent. Moreover, tamoxifen acts as a full
estrogen agonist in T3-dependent responses but behaves as an antiestrogen in T3
independent responses. T3 directly induces a variety of metabolic enzymes and
proteins, and also induces rat growth hormone (GH). Thus, some T3-dependent
tamoxifen effects might reflect modulation of GH rather than T3 actions. To
address this issue, tamoxifen effects on somatotropic and metabolic actions of T3
and GH were compared in ovariectomized rats with methimazole-induced
hypothyroidism. Rats were given T3 (10 micrograms/kg/day) or ovine GH (2
mg/kg/day) with or without tamoxifen (0.5 mg/kg/day) for 30 days. GH was poorly
effective in producing a sustained increase in somatic growth in hypothyroid rats
compared to T3; nonetheless, GH effects to increase body weight, tibia length and
serum insulin-like growth factor I while decreasing fat mass and evoking small
increases in body temperature were not inhibited by tamoxifen. Tamoxifen also did
not inhibit GH trends to increase tibia bone mineral density. T3 increased body
temperature, insulin-like growth factor I levels and all measures of somatic
growth and, unlike GH, increased food intake and tended to decrease tibia bone
mineral density. Tamoxifen inhibited the somatotropic actions of T3 (including
increases in insulin-like growth factor I levels), and produced significant
increases in tibia bone mineral density only in T3-treated rats. Tamoxifen had no
effect on T3 actions to increase food intake or body temperature. T3 alone
increased fat mass and exhibited a tendency to decrease serum triglycerides:
tamoxifen had no effect on these parameters in the absence of T3. However,
coadministration of tamoxifen with T3 produced a marked decrease in fat mass and
increased serum triglycerides. GH had no effect on serum triglycerides in either
the presence or absence of tamoxifen. Serum glucose levels appeared normal in all
groups. The data indicate that multiple tamoxifen effects on growth and
metabolism may reflect modulation of T3 rather than GH actions.
PMID- 9655885
TI - Angiotensin 1-7 induces bradykinin-mediated relaxation in porcine coronary
artery.
AB - Angiotensin 1-7 (Ang 1-7) has been reported to induce relaxation which is
partially blocked by a kinin receptor antagonist. We investigated the
relationship between kinins and angiotensin peptides with use of preconstricted
isolated pig coronary arteries. Ang 1-7 alone (up to 10(-5) M) had no relaxant
effect. Bradykinin (BK) (10(-10)-10(-7) M) induced transient relaxation,
returning to basal tone, although BK remained in the bath. In these BK-stimulated
rings, Ang 1-7 but not BK (both 5 x 10(-6) M) again relaxed the rings by
approximately 50%. This relaxation was blocked by a BK B2 antagonist, a kininase,
and a nitric oxide synthase inhibitor. Ang 1-7 inhibited purified angiotensin
converting enzyme (ACE) by 30 +/- 3.5% (n = 4) at 10(-6) M. However, in BK
pretreated rings, the ACE inhibitor ramiprilat did not induce relaxation, nor did
it affect the relaxant response to Ang 1-7, which suggests that the effect of Ang
1-7 was not caused by ACE inhibition. Ang 1-7-induced vasodilation was reduced by
69.9 +/- 6.2% by an AT2 receptor blocker, PD-123319, and 29.3 +/- 7.3% by an AT1
antagonist, losartan. Neither the nonselective AT1/AT2 receptor antagonist
sarthran nor saralasin inhibited the response to Ang 1-7. Ang II did not elicit
relaxation either alone or in the presence of losartan, which suggests that
activation of AT2 receptors does not cause relaxation. Thus, in the presence of
bradykinin, Ang 1-7 relaxes pig coronary arteries via a PD-123319-sensitive
mechanism involving nitric oxide, kinins and the BK B2 receptor. The kallikrein
kinin and renin-angiotensin systems may be linked through the interaction of Ang
1-7 and BK.
PMID- 9655886
TI - Pharmacological characterization of an FP prostaglandin receptor on rat vascular
smooth muscle cells (A7r5) coupled to phosphoinositide turnover and intracellular
calcium mobilization.
AB - An FP prostaglandin (PG) receptor on the A7r5 rat aorta smooth muscle cell line
has been characterized by assays of phosphoinositide (PI) turnover and
intracellular calcium mobilization stimulated by structurally diverse PGs. In the
PI turnover assay, cloprostenol was the most potent PG tested, with a potency
(EC50) of 0.84 +/- 0.06 nM (mean +/- S.E.M., n = 34), and was a full agonist.
Other known FP receptor agonists tested in this assay had efficacies > or = 85%
of the cloprostenol value and high potencies: 16-phenoxy PGF2 alpha (2.05 +/-
0.19 nM), 17-phenyl PGF2 alpha (2.80 +/- 0.59 nM), fluprostenol (4.45 +/- 0.19
nM), PGF2 alpha (30.9 +/- 2.82 nM) and PhXA85 (43.5 +/- 11.4 nM). Other classes
of PGs evaluated (PGD2, enprostil, 17-phenyl PGE2, PGE2, sulprostone and U-46619)
were less potent and less efficacious than the FP receptor agonists, or were
inactive. For a large group of standard PGs evaluated in the PI turnover assay,
both potencies and efficacies correlated well with those reported for the FP
receptor of Swiss mouse 3T3 fibroblasts. The potencies of fluprostenol and PGF2
alpha as stimuli of intracellular calcium mobilization matched well their
potencies in the PI turnover assay, but fluprostenol had twice the efficacy of
PGF2 alpha. Both signaling responses stimulated by fluprostenol were
significantly inhibited by U73122, a selective inhibitor of phosphoinositide
turnover (IC50 = 1.25 +/- 0.16 microM for PI turnover), and by chelation of
calcium in the medium. Together with the PI turnover data, these studies of
intracellular calcium mobilization linked to activation of the FP receptor,
provide additional characterization of the pharmacological properties of this
receptor.
PMID- 9655887
TI - Novel chemically modified oligonucleotides provide potent inhibition of P
glycoprotein expression.
AB - One major form of multiple drug resistance (MDR) to cancer therapeutic agents is
mediated by overexpression of P-glycoprotein, a membrane ATPase that serves as a
drug efflux pump. In humans, this protein is the product of the MDR1 gene. We
have used chemically modified antisense oligonucleotides to reduce expression of
P-glycoprotein in multidrug-resistant fibroblasts and colon carcinoma cells.
Although several types of oligonucleotides were tested, compounds having a
phosphorothioate backbone and a methoxyethoxy (ME) group at the 2' position of
the ribose ring proved to have the greatest potency. Thus, phosphorothioate 2'-ME
oligonucleotides directed against either the AUG codon region or the stop codon
region of the MDR1 message produced substantial (50-70%) inhibition of P
glycoprotein expression at concentrations of < or = 50 nM. In addition, such
treatment resulted in augmented drug uptake as measured by flow cytometry.
Unmodified phosphorothioate compounds of the same sequence were active only in
the micromolar range. We also tested the ability of several potential delivery
agents to enhance the pharmacological effectiveness of anti-MDR1
oligonucleotides. Both commercial Lipofectin, a well known liposomal transfection
agent, and a liposomal preparation based on a novel "facial amphiphile" were
effective in enhancing their pharmacological effects of antisense
oligonucleotides. A Starburst dendrimer, a type of cationic polymer, was also
effective in oligonucleotide delivery. This report emphasizes that significant
improvements in antisense pharmacology can be made through judicious use of both
chemical modifications of oligonucleotides and appropriate delivery systems.
PMID- 9655888
TI - Blocking of classical complement pathway inhibits endothelial adhesion molecule
expression and preserves ischemic myocardium from reperfusion injury.
AB - Myocardial injury after ischemia (I) and reperfusion (R) is related to leukocyte
activation with subsequent release of cytokines and oxygen-derived free radicals
as well as complement activation. In our study, the cardioprotective effects of
exogenous C1 esterase inhibitor (C1 INH) were examined in a rat model of
myocardial I + R (i.e., 20 min + 24 hr or 48 hr). The C1 INH (10, 50 and 100
U/kg) administered 2 min before reperfusion significantly attenuated myocardial
injury after 24 hr of R compared to vehicle treated rats (P < .001). Further,
cardiac myeloperoxidase activity (i.e., a marker of PMN [polymorphonuclear
leukocyte] accumulation) in the ischemic area was significantly reduced after C1
INH treatment compared to vehicle treated animals (0.81 +/- 0.1, 0.34 +/- 0.13,
0.13 +/- 0.1 vs. 1.44 +/- 0.3 U/100 mg tissue, P < .001). In addition, C1 INH
(100 U/kg) significantly attenuated myocardial injury and neutrophil infiltration
even after 48 hr of reperfusion compared to vehicle treatment.
Immunohistochemical analysis of ischemic-reperfused myocardial tissue
demonstrated activation of classical complement pathway by deposition of C1q on
cardiac myocytes and cardiac vessels. In addition, expression of the endothelial
adhesion molecules P-selectin and intercellular adhesion molecule 1 (ICAM-1) was
observed after reperfusion of the ischemic myocardium. In this regard, C1 INH
administration abolished expression of P-selectin and ICAM-1 on the cardiac
vasculature after myocardial ischemia and reperfusion. Blocking the classical
complement pathway by exogenous C1 INH appears to be an effective means to
preserve ischemic myocardium from injury after 24 and 48 hr of reperfusion. The
mechanisms of this cardioprotective effect appears to be due to blocking of
complement activation and reduced endothelial adhesion molecule expression with
subsequent reduced PMN-endothelium interaction, resulting in diminished cardiac
necrosis.
PMID- 9655889
TI - The carbohydrate sialyl Lewis(x) (sLe(x)) sulfated glycomimetic GM2941 attenuates
glucan-induced pulmonary granulomatous vasculitis in the rat.
AB - We examined the protective effects of GM2941, a sulfated glycomimetic of the
complex carbohydrate sialyl Lewis(x), in a model of pulmonary granuloma
development. This study was based on the rationale that formation of glucan
induced lung granulomas is dependent on neutrophils and that sialyl Lewis(x)
glycomimetic (GM2941) interferes, in vitro, with P-selectin-dependent neutrophil
endothelial adhesive interactions. Infusion of particulate yeast cell wall glucan
into rats results in the rapid (48 hr) formation of monocyte/macrophage-rich
angiocentric pulmonary granulomas. Development of granulomas exhibits a temporal
pattern characterized by the early, transient influx of neutrophils into blood
vessel walls at sites of glucan embolization, followed by accumulation of
monocytes and macrophages that constitute the definitive angiocentric lesions.
Within 1 hr after the infusion of glucan, immunohistochemical analysis revealed
up-regulation of blood vessel wall-associated P-selectin. Previous studies
utilizing neutrophil-depleted animals have revealed that neutrophils, although
not present in definitive lesions, are required for full granuloma development.
The potential of GM2941 to inhibit neutrophil-endothelial cell adhesive
interactions was demonstrated by the ability of the compound to inhibit P
selectin-mediated adhesion to histamine-stimulated HUVECs. Infusion of GM2941
retarded pulmonary granuloma development in a dose-dependent manner. Whole-lung
myeloperoxidase activity, measured at the time of peak neutrophil accumulation,
was significantly reduced in animals pretreated with GM2941 (30 mg/kg, 24
microM/kg), which suggests that this compound affords protection, at least in
part, through impedance of neutrophil recruitment. These data indicate that
GM2941 affords a significant degree of protection against granuloma formation
associated with glucan infusion, probably through the interruption of neutrophil
recruitment.
PMID- 9655890
TI - In vivo distribution and metabolism of a phosphorothioate oligonucleotide within
rat liver after intravenous administration.
AB - In the rat, the liver represents a major site of phosphorothioate
oligodeoxynucleotide deposition after i.v. administration. For this reason, we
examined the intracellular fate of ISIS 1082, a 21-base heterosequence
phosphorothioate oligodeoxynucleotide, isolated from parenchymal and
nonparenchymal cell types after systemic dosing using established perfusion and
separation techniques followed by CGE. Isolated cells were further fractionated
into nuclear, cytosolic and membrane constituents to assess the intracellular
localization, distribution and metabolic profiles as a function of time and dose.
After a 10-mg/kg i.v. bolus, intracellular drug levels where maximal after 8 hr
and diminished significantly thereafter, suggesting an active efflux mechanism or
metabolism. Nonparenchymal (i.e., Kupffer and endothelial) cells contained
approximately 80% of the total organ cellular dose, and this was equivalently
distributed between the two cell types, while the remaining 20% was associated
with hepatocytes. Nonparenchymal cells contained abundant nuclear, cytosolic and
membrane drug levels over a wide dose range. In contrast, at doses of less than
25 mg/kg, hepatocytes contained significantly less drug with no detectable
nuclear-association. Doses at or above 25 mg/kg appeared to saturate
nonparenchymal cell types, whereas hepatocytes continued to accumulate drug in
all cellular compartments, including the nucleus. Our results suggest that
although pharmacokinetic parameters vary as a function of hepatic cell type,
significant intracellular delivery can be readily achieved in the liver after
systemic administration.
PMID- 9655891
TI - Characterization of [125I]sauvagine binding to CRH2 receptors: membrane
homogenate and autoradiographic studies.
AB - We describe the binding of [125I]tyr(o)sauvagine to membranes of corticotropin
releasing hormone (CRH2) receptor expressing HEK293/EBNA (293ECRH2 alpha) cells.
The binding of [125I]tyr(o)sauvagine to CRH2 receptors was temperature, time and
tissue dependent. Equilibrium was reached in 2 hr at 23 degrees C. Saturation
data best fit a two-site model with affinity constants of 44 pM and 4.1 nM for
high and low affinity states, respectively. The high affinity
[125I]tyr(o)sauvagine binding sites were eliminated with 200 microM Gpp (NH) p,
indicating coupling to G proteins. The rank order potency of peptide analogs of
CRH to inhibit [125I]tyr(o)sauvagine binding to CRH2 alpha receptors was:
urotensin > sauvagine = urocortin > alpha-helical CRH9-41 > rh-CRH >> o-CRH. This
was in contrast to the rank order potency of the peptides at inhibiting
[125I]tyr(o)oCRH binding to CRH, receptors: urotensin > urocortin > r/h-CRH > o
CRH = sauvagine > alpha-helical CRH9-41. We show that two recently identified
small molecule CRH antagonists with nanomolar potency at the CRH1 receptor, have
little or no affinity for CRH2 alpha receptors as labeled by
[125I]tyr(o)sauvagine. Two selective CRH1 receptor antagonists enabled us to
examine comparative densities of CRH1 and CRH2 receptors in several brain areas.
We also used [125I]tyr(o)sauvagine in combination with a specific CRH1 antagonist
to examine the anatomic distribution of CRH2 receptors using receptor
autoradiography. With a few notable exceptions the CRH2 receptors demonstrated
autoradiographically in this study match the data obtained by in situ
hybridization studies on the localization of CRH2 mRNA. The anatomic overlap of
the autoradiographic and in situ hybridization data suggest that CRH2 receptors
are postsynaptic. This study demonstrates the utility of using
[125I]tyr(o)sauvagine to study cloned CRH2 receptors expressed in cell lines. In
addition, [125I]tyr(o)sauvagine used in conjunction with saturating
concentrations of a specific CRH1 receptor antagonist allows the study of CRH2
receptors in brain tissues using both in vitro homogenate binding and receptor
autoradiography techniques.
PMID- 9655892
TI - Paracrine endothelin signaling in the control of basal cell proliferation in
guinea pig tracheal epithelium.
AB - Immunofluorescent analyses revealed distinct cellular/subcellular localization of
endothelin (ET) receptors and ET-1 in the epithelial cell layer of guinea pig
trachea. ETA was expressed predominantly in the basal cells. ETB was expressed
predominantly in the ciliated columnar cells and was polarized at the apical side
of the cell body within the cells. Anti-ET-1-immunoreactive cytoplasmic granules
were contained in the secretory cells that were scattered throughout the
epithelial layer. Cell proliferation assays with immersion cultures of
differentially plated cells (basal cell-enriched, non-basal cell-enriched and
mixed cell cultures) indicated the presence of paracrine ET-1 signaling pathways
that transmit both positive and negative effects on the basal cell proliferation.
Direct activation of ETA expressed on the basal cells caused enhancement of their
growth, whereas that of ETB expressed on the ciliated columnar cells caused
suppression of the basal cell growth. The latter effect was transmitted by nitric
oxide whose production was stimulated by ETB activation. Furthermore, blockade of
either ETA or ETB compromised the epithelial cell layer formation under the air
interphase culture, which indicates the dependence of tracheal epithelial
remodeling on a balance between the positive and negative effects of ET-1 on the
basal cell growth.
PMID- 9655893
TI - Alteration in regulation of serotonin release in rat dorsal raphe nucleus after
prolonged exposure to morphine.
AB - Regulation of serotonin (5-HT) release may be altered during the development of
opioid tolerance and dependency. To test this hypothesis, changes in
extracellular 5-HT during prolonged administration of morphine were determined by
microdialysis in the dorsal raphe nucleus (DRN) of freely behaving rats. Morphine
or placebo pellets were implanted s.c. As compared to placebo, morphine pellets
induced a sustained, approximately 50% increase in DRN 5-HT and a significant
elevation in hot plate latency during the 12-hr period after implantation. One
week later DRN 5-HT had returned to control levels, and implanting additional
morphine pellets had no effect on 5-HT or hot plate latency. One day after
removing the pellets from rats exposed to morphine for 2 wk, acute challenge with
morphine (20 mg/kg, s.c.) had a significantly smaller effect on 5-HT in the DRN
as compared to the placebo treatment group. Administration of naltrexone to rats
implanted with morphine pellets for 2 wk induced signs of withdrawal and a
significant decrease in DRN 5-HT. These results suggest that the regulation of 5
HT release is altered during the development of tolerance to morphine. Thus, DRN
5-HT may be one of the factors involved in the changes in physiology and
behavioral state during opioid withdrawal.
PMID- 9655894
TI - Crosstalk between alpha-1A and alpha-1B adrenoceptors in neonatal rat myocardium:
implications in cardiac hypertrophy.
AB - The myocardial effect of alpha-1A adrenoceptor (alpha-1 AR) agonists in neonatal
rats are mediated by alpha-1A AR and not by alpha-1B AR, although both receptor
subtypes are equally expressed; the functions of alpha-1B AR are not known. Here,
we report that alpha-1 B ARs inhibit the activities of alpha-1A ARs in neonatal
rat myocardium so that the inactivation of alpha-1 B ARs by chloroethylclonidine
(CEC) potentiated the effects of nonselective alpha-1 AR agonist phenylephrine
(PE) on myocardial protein synthesis and early gene (c-fos and c-jun) expression.
CEC did not modify the hypertrophic effect of angiotensin II. The potentiation of
the effects of PE by CEC was associated with a translocation of Ca(++)-dependent
protein kinase C (PKC)alpha, which did not occur in the absence of CEC. Alpha-1A
AR-selective agonist A61603 was approximately 1000-fold more potent than PE as a
positive inotropic agent; it caused the translocation of PKC alpha, which was not
affected by CEC. 5-Methylurapidil antagonized the effects of PE and A61603,
suggesting that these were mediated via alpha-1A ARs. Alpha-1D AR antagonist BMY
7378 did not modify PE-induced translocation of PKC. CEC potentiated the effects
of PE on Ca++ transients in Fura 2-AM-loaded dispersed cardiomyocytes, and this
potentiation was prevented by nifedipine. In whole-cell patch-clamp recordings of
cultured cardiomyocytes, CEC potentiated the effect of norepinephrine on Ca++
channel currents, which was blocked by 5-methylurapidil. We conclude that alpha
1A ARs are positively and alpha-1B ARs are negatively coupled to nifedipine
sensitive Ca++ channels, possibly via Gi protein, and this antagonistic
relationship between alpha-A AR and alpha-1B AR in the neonatal heart might be
required physiologically for normal alpha-1 AR-mediated responses and myocardial
development.
PMID- 9655895
TI - The role of dopamine D4 receptor in the induction of behavioral sensitization to
amphetamine and accompanying biochemical and molecular adaptations.
AB - Our studies examined the role of dopamine D4 receptors in the induction of
behavioral sensitization to amphetamine (Amp) and accompanying neurochemical and
molecular adaptive responses using a highly selective D4 antagonist, PNU-101387G.
Behavioral sensitization to an acute challenge of Amp (2 mg/kg, s.c.) was
observed in rats pretreated with five daily doses of Amp (2 mg/kg/d, s.c.)
followed by 7-day withdrawal. Interestingly, coadministration of PNU-101387G with
Amp during pretreatment completely blocked the sensitized response to an acute
Amp challenge. The behavioral sensitization and its blockade by the D4 antagonist
were observed in the absence of significant differences in cerebellar Amp levels
among the various pretreatment groups. Accompanying behavioral sensitization were
two postsynaptic neuroadaptive responses: reduction in the ability of Amp to
induce c-fos gene expression in the infralimbic/ventral prelimbic cortex and NT/N
mRNA in the accumbal shell. However, concurrent blockade of D4 receptors during
Amp pretreatment prevented the refractoriness in c-fos and NT/N responsiveness to
acute Amp. We observed also a presynaptic neuroplastic response associated with
the behavioral sensitization: a significant augmentation in the ability of Amp to
increase extracellular dopamine concentrations in the nucleus accumbens shell. As
with the behavioral sensitization and associated postsynaptic adaptive responses,
concurrent administration of PNU-101387G with Amp during pretreatment blocked the
augmentation in Amp-induced dopamine release. Taken together, these data
demonstrate that dopamine D4 receptors play an important role in the induction of
behavioral sensitization to Amp and accompanying adaptations in pre- and
postsynaptic neural systems associated with the mesolimbocortical dopamine
projections.
PMID- 9655896
TI - Cocaine administered in vitro to brain slices from rats treated with cocaine
chronically in vivo results in a gamma-aminobutyric acid receptor-mediated
hyperpolarization recorded from the dorsolateral septum.
AB - Previous reports of membrane hyperpolarizations, associated with acute
application of cocaine, have been recorded from brain slice preparations
containing aminergic nuclei and have always been attributed to cocaine's ability
to elevate levels of local biogenic amines followed by activation of their
receptors. The majority of these studies were conducted with brain slices
obtained from rats that had not received prior chronic in vivo treatment with
cocaine. We observed that cocaine alone, at 3 microM, could induce a membrane
hyperpolarization (COC-HYP) in 100% of rat dorsolateral septal nucleus (DLSN)
neurons from brain slices of rats treated chronically with cocaine for either 14
or 28 days in vivo. The DLSN is a nucleus absent of biogenic amine cell bodies,
but does contain biogenic amine terminals with GABAergic cell bodies and
terminals. Cocaine applied to brain slices from rats not previously administered
cocaine or administered cocaine for up to seven days in vivo yielded a maximum
incidence of COC-HYPs at only 50%. COC-HYPs recorded from DLSN neurons were not
blocked by previous treatment with amine receptor antagonists or by a TTX and
zero calcium medium. Based on these results, the ability of DLSN neurons to
respond to a cocaine challenge with a COC-HYP did not involve inhibition of amine
reuptake/uptake or action potential release of neuroactive substances. Rather,
the COC-HYP, with an apparent reversal potential of -80 mV, was reduced by the
GABA receptor antagonists-bicuculline and CGP-55845A. Lowering extracellular Na+
or Cl-, lowering of temperature, or previous superfusion with the GABA uptake
blocker NO-711 could block the COC-HYP. In summary, our data suggest that COC
HYPs, after application of a cocaine challenge to brain slices from rats treated
chronically (14-28 days, but not acutely, 7 days) with cocaine are due to cocaine
induced changes in GABA release and/or transporter function. The latter changes
in transporter function may involve the reversal of the GABA transporter with
release of GABA and subsequent activation of postsynaptic GABAA and GABAB
receptors.
PMID- 9655897
TI - Effect of N-acetylcysteine on heat shock protein induction by acetaminophen in
mouse liver.
AB - It was previously shown that a necrogenic dose of acetaminophen (APAP) induced
the 25- and 70-kDa heat shock proteins (hsp25 and hsp70i) in mouse liver, whereas
nonnecrogenic doses failed to alter the level of either hsp. A strong correlation
between the intralobular sites of APAP arylation of protein and hsp induction
suggested that APAP-induced protein denaturation may play a role in triggering
hsp induction. This study was conducted to determine whether APAP arylation of
protein without concurrent toxicity could cause hsp induction. APAP (250 mg/kg
i.p.) hepatotoxicity was eliminated using N-acetylcysteine (NAC, 300 mg/kg i.p.)
or the cytochrome P-450 inhibitor diallyl sulfide (200 mg/kg p.o.). NAC did not
inhibit APAP arylation of protein when administered 1 or 3 hr after the APAP dose
but decreased binding by approximately 50% when administered at the same time as
the APAP dose. Even though APAP hepatotoxicity was blocked by NAC administered 0
or 1 hr after the APAP dose, NAC did not inhibit the induction of hsp25 or
hsp70i, indicating that APAP arylation of protein may play a key role in
triggering hsp induction. Diallyl sulfide blocked APAP arylation of protein,
hepatotoxicity, and induction of both hsps. These data are consistent with the
hypothesis that toxicant adduction of protein triggers hsp induction.
PMID- 9655898
TI - Handling of doxorubicin by the LLC-PK1 kidney epithelial cell line.
AB - The characteristics of doxorubicin handling have been studied in the cultured
kidney epithelial cell line LLC-PK1, which has structure and function similar to
those of renal tubular cells and expresses P-glycoprotein. The uptake of
doxorubicin by LLC-PK1 cells was time dependent, reaching a steady state at about
4 hr, and reduced at low temperature; the initial uptake was saturable. The
efflux of doxorubicin from LLC-PK1 cells was also temperature dependent but, even
at 37 degrees C, a significant percentage of the drug remained associated with
the cells after 180 min, which suggests a strong cellular binding, and the
fluorescence microscopy revealed that the drug was concentrated in intracellular
organelles. Substances that are substrates for P-glycoprotein, such as verapamil,
vinblastine, vincristine and quinidine, significantly increased doxorubicin
concentrations in LLC-PK1 cells. Similar results were obtained with the metabolic
inhibitors sodium metavanadate and 2,4-dinitrophenol. On the other hand, the
uptake was not affected by the classic organic cation transport drugs cimetidine,
decynium 22 or decynium 24, nor by the organic anion drug probenecid. These
results indicate that, in LLC-PK1 cells, doxorubicin enters by passive diffusion,
is trapped in intracellular organelles and then is extruded from cells by a
mechanism that probably involves P-glycoprotein. On the contrary, substances that
interfere with the renal organic cation or anion secretory system have no effect
on doxorubicin net accumulation in these cells.
PMID- 9655899
TI - Long-term beta adrenoceptor-mediated alteration in contractility and expression
of phospholamban and sarcoplasmic reticulum Ca(++)-ATPase in mammalian ventricle.
AB - We studied the influence of prolonged administration of the beta adrenoceptor
agonist isoproterenol on contractile parameters and expression of sarcoplasmic
reticulum (SR) Ca(++)-ATPase and phospholamban, genes important for Ca++ uptake
into the SR. Isoproterenol (Iso), 0.9% NaCl (Ctr), propranolol (Prop) or Iso plus
Prop were administered to rats by subcutaneous infusion with osmotic minipumps
for 1, 2, 3, 4, 8, 13 and 26 days, respectively. The positive inotropic effect of
Iso was impaired in rats pretreated with Iso in vivo. Iso pretreatment shortened
time to peak tension (TPT) by 28%, time of relaxation (RT) by 27% and total
contraction time (TCT) by 27% compared with the appropriate controls (day 2). The
shortening of time-dependent contractile indices started after 1 day of Iso
pretreatment, reached a maximum after 2 days and remained reduced for 4 days.
Longer treatment by Iso failed to affect time parameters, whereas the positive
inotropic effect of Iso added to the isolated muscles persisted. The shortened
contractile time parameters were accompanied by diminished mRNA and protein
expression of phospholamban (PLB) and SR-Ca(++)-ATPase (SERCA). The mRNA levels
for PLB and SERCA were maximally reduced by 31 +/- 1.3% and 41 +/- 1.4% in the
Isopretreated group (2 days) respectively. The reduced mRNA levels were
accompanied by reduced levels of the corresponding proteins. It is concluded that
altered levels of PLB and SERCA probably account for the noted changes in
contractile time parameters in the mammalian heart.
PMID- 9655900
TI - Lithium protects rat cerebellar granule cells against apoptosis induced by
anticonvulsants, phenytoin and carbamazepine.
AB - We have studied the neuroprotective actions of lithium against various insults in
cultured cerebellar granule cells of rats. The anticonvulsants, phenytoin and
carbamazepine, have been shown to induce apoptosis of cerebellar granule cells at
high concentrations. Here we found that co-presence of LiCl (1-10 mM) dose
dependently protected against phenytoin (20 microM)- and carbamazepine (100
microM)-induced neuronal apoptosis as assessed by 3-(4,5-dimethylthiazol-2-yl)
2,5-diphenyl-tetrazolium bromide metabolism, morphological inspection, chromatin
condensation and DNA fragmentation. These neuroprotective effects were not
prevented by inclusion of myoinositol nor mimicked by a potent inositol
monophosphatase inhibitor, suggestive of a mechanism independent of inositol
monophosphatase blockade. Lithium also significantly protected against apoptosis
of cerebellar granule cells induced by aging of the cultures. Additionally,
lithium suppressed death of cerebellar granule cells exposed to a low
concentration of extracellular potassium. In contrast, it had no protective
effect on cell death induced by Ca++ ionophores, a Na+ channel opener, a protein
kinase inhibitor, a nitric oxide donor or H2O2. Thus, lithium has robust
neuroprotective effects against apoptotic cell death induced by multiple insults
with limited selectivity. These actions provide a new avenue to study the
molecular and cellular mechanisms of this drug.
PMID- 9655901
TI - Enhanced endocytosis in cultured human breast carcinoma cells and in vivo
biodistribution in rats of a humanized monoclonal antibody after cationization of
the protein.
AB - For monoclonal antibody therapeutics to access target antigen in extravascular
compartments, an antibody drug delivery technology is required that has the dual
properties of 1) transendothelial migration of the antibody and 2) endocytosis of
the antibody into the target cell. These two objectives may be achieved with
antibody cationization, and the present studies examine the feasibility of
cationizing the humanized 4D5 monoclonal antibody directed against the p185HER2
oncogenic protein. The cationized antibody binds to the p185HER2 extracellular
domain with an ED50 of 35 micrograms/ml and inhibits SK-BR3 cell proliferation
similar to the native antibody. Confocal microscopy showed that although there
was binding of the native 4D5 antibody to the plasma membrane of SK-BR3 cells,
this antibody was confined to the periplasma membrane space with minimal
endocytosis into the cell. In contrast, robust internalization of the cationized
4D5 antibody by the SK-BR3 cells was demonstrated by confocal microscopy. The
systemic volume of distribution of the cationized 4D5 antibody was 11-fold
greater than that of the native antibody. In summary, these studies show that a
humanized monoclonal antibody may be cationized with retention of antibody
affinity for the target antigen and biological activity, yet with a marked
alteration in the cellular distribution and pharmacokinetics in vivo.
PMID- 9655902
TI - Expression of estrogen sulfotransferase in MCF-7 cells by cDNA transfection
suppresses the estrogen response: potential role of the enzyme in regulating
estrogen-dependent growth of breast epithelial cells.
AB - Estrogen sulfotransferase (EST) is a cytosolic enzyme that catalyzes the
sulfonation of estrogens at the 3-hydroxyl position by use of 3'-phosphoadenosine
5'-phosphosulfate as an activated sulfate donor. Although largely known and
studied as a phase II metabolic enzyme with prominent expression in the liver,
the high substrate specificity of EST (with a high Vmax/Km value for estrogen)
suggests that expression of the enzyme in extrahepatic, estrogen target tissues,
such as the breast epithelium, may constitute an effective mechanism for local
estrogen regulation as well. In this study, we have evaluated the physiological
significance of EST expression by cDNA transfection studies with use of the
estrogen-dependent MCF-7 breast cancer cell line as a model system. We show that
expression of EST in MCF-7 cells effectively reduces the cells' response to
physiological concentrations of estradiol (10 nM) by up to 70% as determined in
an estrogen-responsive reporter gene assay. In addition, we demonstrate that
expression of EST similarly inhibits estrogen-stimulated DNA synthesis and cell
proliferation by 21% and 46%, respectively. (The thymidine incorporation rate was
measured 3 days after and the cell numbers were counted 8 days after
transfection.) These results provide direct evidence for the functional
significance of in situ EST expression in the breast epithelium and suggest that
abnormal regulation of the enzyme may have pathological implications in the
development and maintenance of hormone-dependent breast carcinomas.
PMID- 9655903
TI - An investigation of the relationship between estrogen, estrogen metabolites and
blood cholesterol levels in ovariectomized rats.
AB - 17 beta-Estradiol (E2) has long been known for protecting against coronary heart
disease by lowering cholesterol levels in premenopausal women. A recent study in
our laboratory suggested that two hydroxylated metabolites of E2 possess similar
hypocholesterolemic effects in male rats. This effect has been further
investigated with additional estrogen metabolites in ovariectomized rats with a
view toward mimicking the true postmenopausal situation in humans. Their effects
in reproductive tissues were also evaluated histologically. Fundamentally, the
following issues were addressed: (1) Do oxidized metabolites of estradiol lower
total cholesterol levels? (2) Can a hypocholesterolemic effect be achieved
without eliciting estrogenic activities on reproductive tissues? The results of
this investigation showed that a number of oxygenated metabolites of estradiol
can lower cholesterol levels. Among them, 4-hydroxyestradiol (4-OHE2) produced a
striking hypocholesterolemic effect and a substantial uterotropic effect. 2
Hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-meoE2) and 2-methoxyestrone (2
meoE1) produced a significant decrease in cholesterol levels at doses that did
not produce significant uterotropic effects.
PMID- 9655905
TI - Identification of a new metabolite of CPT-11 (irinotecan): pharmacological
properties and activation to SN-38.
AB - Irinotecan, or CPT-11 (7-ethyl-10-[4-(1-piperidino)-1
piperidino]carbonyloxycamptothecine++ +), is a water-soluble derivative of
camptothecine with promising activity against several types of malignancies. In
addition to 7-ethyl-10-hydroxycamptothecine (SN-38), its active metabolite, we
were able to identify several metabolites in the plasma of patients treated with
this drug, especially an oxidative metabolite, 7-ethyl-10[4-N-(5-aminopentanoic
acid)-1-piperidino] carbonyloxy-camptothecine. During our study of the
biosynthesis of 7-ethyl-10[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxy
camptothecine from CPT-11 by human liver microsomes, we were able to detect
another quantitatively important polar metabolite, which was also present in the
plasma and urine of patients treated with CPT-11. On the basis of preliminary
experiments, the structure of this compound was postulated to be 7-ethyl-10-(4
amino-1-piperidino)carbonyloxycamptothecine, and this structure was synthesized
by Rhone-Poulenc Rorer. Urine samples and human liver microsomal extracts were
studied by high-performance liquid chromatography/atmospheric pressure chemical
ionization/tandem mass spectrometry to identify its structure formally. The
identification of the metabolite was supported by identical retention time, mass
to-charge ratio and tandem mass spectrometry fragmentation as a synthetic
standard. Like irinotecan, 7-ethyl-10-(4-amino-1-piperidino)
carbonyloxycamptothecine was a weak inhibitor of cell growth of P388 cells in
culture (IC50 = 3.4 micrograms/ml vs. 2.8 micrograms/ml for irinotecan and 0.001
microgram/ml for SN-38). It was also a poor inducer of topoisomerase I-DNA
cleavable complexes (100-fold less potent than SN-38). However, unlike 7-ethyl
10[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxy-camptothecine, this new
metabolite could be hydrolyzed to SN-38 by human liver microsomes and purified
human liver carboxylesterase, though to a lesser extent than irinotecan. This
compound can therefore contribute to the activity and toxicity profile of
irinotecan in vivo.
PMID- 9655904
TI - In vitro biological characterization and antiangiogenic effects of PD 166866, a
selective inhibitor of the FGF-1 receptor tyrosine kinase.
AB - Through direct synthetic efforts, we discovered a small molecule that is a
nanomolar inhibitor of the human fibroblast growth factor-1 receptor (FGFR)
tyrosine kinase. PD 166866, a member of a new structural class of tyrosine kinase
inhibitors, the 6-aryl-pyrido[2,3-d]pyrimidines, was identified by screening a
compound library with assays that measure protein tyrosine kinase activity. PD
166866 inhibited human full-length FGFR-1 tyrosine kinase with an IC50 value of
52.4 +/- 0.1 nM and was further characterized as an ATP competitive inhibitor of
the FGFR-1. In contrast, PD 166866 had no effect on c-Src, platelet-derived
growth factor receptor-beta, epidermal growth factor receptor or insulin receptor
tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and
CDK4 at concentrations as high as 50 microM. PD 166866 was a potent inhibitor of
basic fibroblast growth factor (bFGF)-mediated receptor autophosphorylation in
NIH 3T3 cells expressing endogenous FGFR-1 and in L6 cells overexpressing the
human FGFR-1 tyrosine kinase, confirming a tyrosine kinase-mediated mechanism. PD
166866 also inhibited bFGF-induced tyrosine phosphorylation of the 44- and 42-kDa
(ERK 1/2) mitogen-activated protein kinase isoforms in L6 cells, presumably via
inhibition of bFGF-stimulated FGFR-1 tyrosine kinase activation. PD 166866 did
not inhibit platelet-derived growth factor, epidermal growth factor or insulin
stimulated receptor autophosphorylation in vascular smooth muscle, A431 or NIHIR
cells, respectively, further supporting its specificity for the FGFR-1. In
addition, daily exposure of PD 166866 to L6 cells at concentrations from 1 to 100
nM resulted in a concentration-related inhibition of bFGF-stimulated cell growth
for 8 consecutive days with an IC50 value of 24 nM. In contrast, PD 166866 had
little effect on platelet-derived growth factor-BB-stimulated growth of L6 cells
or serum-stimulated vascular smooth muscle cell proliferation. Finally, PD 166866
was found to be a potent inhibitor of microvessel outgrowth (angiogenesis) from
cultured artery fragments of human placenta. These results highlight the
discovery of PD 166866, a new nanomolar potent and selective small molecule
inhibitor of the FGFR-1 tyrosine kinase with potential use as
antiproliferative/antiangiogenic agent for such therapeutic targets as tumor
growth and neovascularization of atherosclerotic plaques.
PMID- 9655906
TI - Sixty years of thiamin diphosphate biochemistry.
AB - The mechanism of ThDP enzymes originates in the anionic (ylid) structure of the
coenzyme. On the other hand, no ylid species (as permanently existing structure)
could be detected by 13C2-NMR studies with PDC (yeast), when the cofactor binds
to the active site. Therefore, the rate of ylid formation as the first step of
the catalytic mechanism distinguishes decisively the power (kcat) of all ThDP
enzymes. 2H/1H-exchange experiments with PDC, TK, PDH and POX have shown that
within the active center of ThDP enzymes (under native pH conditions!) the
aminopyrimidine part generates the essential ylid structure by enhancing the
dissociation rate (acidity) of the C2-H bond up to 4-6 orders of magnitude.
Moreover, it could be proved that the mechanism of substrate activation of PDC
(yeast) is also connected directly with the C2-H activation by the
aminopyrimidine part. Experiments with analogs of ThDP or modified apoenzymes
(via site-directed mutagenesis) have shown that this mechanism requires as
essential elements a hydrogen bond between the pyrimidine N1' atom and a
conserved Glu side chain of the different apoenzymes as well as the (evolutionary
conserved) V-conformation. The latter positions the 4'-amino group in direct
(functional) contact to the C2-H bond. A proposal is discussed, how the 4'
positioned amino group in cooperation with the N1' atom could increase the C2-H
dissociation rate.
PMID- 9655907
TI - Transition-state theoretical interpretation of the catalytic power of pyruvate
decarboxylases: the roles of static and dynamical considerations.
AB - The catalytic power of two thiamin diphosphate (ThDP)-dependent enzymes, yeast
pyruvate decarboxylase (the hysteretically regulated enzyme from Saccharomyces
cerevisiae, SCPDC) and bacterial pyruvate decarboxylase (the unregulated enzyme
from Zymomonas mobilis, ZMPDC), are analyzed by thorough-going application of
transition-state theory, i.e. by a static approach that emphasizes the state
function character of the free energy of activation and takes no explicit account
of dynamical considerations. The overall catalytic reaction is resolved into
manifolds for addition (conversion of free enzyme and substrate to the complex of
enzyme with the pyruvate:ThDP adduct), decarboxylation, and elimination
(conversion of the complex of enzyme with the acetaldehyde:ThDP adduct formed by
decarboxylation into free product and free enzyme). For SCPDC, the addition
manifold is most strongly catalyzed (3x1012-fold, corresponding to net transition
state stabilization of 72 kJ/mol, transition-state stabilization of 83 kJ/mol
diminished by reactant-state stabilization of 11 kJ/mol), the decarboxylation
manifold is least strongly catalyzed (5x107-fold, corresponding to net transition
state stabilization of 41 kJ/mol, transition-state stabilization of 68 kJ/mol
diminished by reactant-state stabilization of 27 kJ/mol), and the elimination
manifold is catalyzed to an intermediate degree (2x1010-fold, corresponding to
net transition-state stabilization of 59 kJ/mol, transition-state stabilization
of 76 kJ/mol diminished by reactant-state stabilization of 17 kJ/mol). A similar
situation holds for ZMPDC. There is no need to make an explicit analysis of
dynamical factors in order to describe the catalytic mechanism and catalytic
power of these complex enzymes.
PMID- 9655908
TI - Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast
Saccharomyces cerevisiae: genetic regulation.
AB - The yeast Saccharomyces cerevisiae utilises external thiamin for the production
of thiamin diphosphate (ThDP) or can synthesise the cofactor itself. Prior to
uptake into the cell thiamin phosphates are first hydrolysed and thiamin is taken
up as free vitamin which is then pyrophosphorylated by a pyrophosphokinase.
Synthesis of ThDP starts with the production of hydroxyethylthiazole and
hydroxymethylpyrimidine. Those are linked to yield thiamin phosphate which is
hydrolysed to thiamin and subsequently pyrophosphorylated. The THI genes encoding
the enzymes of these final steps of ThDP production and of thiamin utilisation
have been identified. Their expression is controlled by the level of thiamin and
a number of regulatory proteins involved in regulated expression of the THI genes
are known. However, the molecular details of the regulatory circuits need to be
deciphered. Since the nucleotide sequence of the entire yeast genome is known we
can predict the number of ThDP-dependent enzymes in S. cerevisiae. Eleven such
proteins have been found: pyruvate decarboxylase (Pdc, three isoforms),
acetolactate synthase, a putative alpha-ketoisocaproate decarboxylase with a
regulatory role in ThDP synthesis and two proteins of unknown function form the
group of Pdc related enzymes. In addition there are two isoforms for
transketolase as well as the E1 subunits of pyruvate dehydrogenase and 2
oxoglutarate dehydrogenase. Expression of most of these genes is either induced
or repressed by glucose. Surprisingly, it has been found recently that expression
of one of the genes for Pdc is repressed by thiamin. In addition, the regulatory
protein Pdc2p was shown to be required for high level expression of both the THI
and the PDC genes. Apparently, the production of ThDP and of the enzymes using
this cofactor is coordinately regulated. Future research will focus on the
elucidation of the molecular mechanisms of this novel type of regulation.
PMID- 9655909
TI - Activation of thiamin diphosphate in enzymes.
AB - Activation of the coenzyme ThDP was studied by measuring the kinetics of
deprotonation at the C2 carbon of thiamin diphosphate in the enzymes pyruvate
decarboxylase, transketolase, pyruvate dehydrogenase complex, pyruvate oxidase,
in site-specific mutant enzymes and in enzyme complexes containing coenzyme
analogues by proton/deuterium exchange detected by 1H-NMR spectroscopy. The
respective deprotonation rate constant is above the catalytic constant in all
enzymes investigated. The fast deprotonation requires the presence of an
activator in pyruvate decarboxylase from yeast, showing the allosteric regulation
of this enzyme to be accomplished by an increase in the C2-H dissociation rate of
the enzyme-bound thiamin diphosphate. The data of the thiamin diphosphate
analogues and of the mutant enzymes show the N1' atom and the 4'-NH2 group to be
essential for the activation of the coenzyme and a conserved glutamate involved
in the proton abstraction mechanism of the enzyme-bound thiamin diphosphate.
PMID- 9655910
TI - Structure and expression of an asparaginyl-tRNA synthetase gene located on
chromosome IV of Arabidopsis thaliana and adjacent to a novel gene of 15 exons.
AB - The gene AtNS1 coding for an asparaginyl-tRNA synthetase and located on
chromosome IV of Arabidopsis thaliana has been characterized. AtNS1 is the first
asparaginyl-tRNA synthetase gene described in higher plants. The genomic
environment of AtNS1 has been studied, as well as a partial cDNA of a second
homologous asparaginyl-tRNA synthetase gene, AtNS2. Both AtNS1 and AtNS2 exhibit
the highest similarity with prokaryotic homologues. A large novel gene of 15
exons, named AtG2484-1, is located adjacent to AtNS1. AtG2484-1 shows features
rarely described in plants including large exons and one 3' non-coding exon. PCR
and Northern analyses were carried out to obtain information about the expression
of these genes in various A. thaliana tissues.
PMID- 9655911
TI - Thiamin-dependent enzymes as catalysts in chemoenzymatic syntheses.
AB - Enzymes are increasingly being used to perform regio- and enantioselective
reactions in chemoenzymatic syntheses. To utilize enzymes for unphysiological
reactions and to yield novel products, a broad substrate spectrum is desirable.
Thiamin diphosphate (ThDP)-dependent enzymes vary in their substrate tolerance
from rather strict substrate specificity (phosphoketolases, glyoxylate
carboligase) to more permissive enzymes (transketolase, dihydroxyacetone
synthase, pyruvate decarboxylase) and therefore differ in their potential to be
used as biocatalysts. We give an overview of the known substrate spectra of ThDP
dependent enzymes and present examples of multi-enzyme or chemoenzymatic
approaches which involve ThDP-dependent enzymes as biocatalysts to obtain
pharmaceutical compounds as ephedrine and glycosidase inhibitors, sex pheromones
as exo-brevicomin, 13C-labeled metabolites, and other intermediates as 1
deoxyxylulose 5-phosphate, a precursor of vitamins and isoprenoids.
PMID- 9655912
TI - Expression of murine H1 histone genes during postnatal development.
AB - Murine genes encoding the seven H1 histone isoforms H1.1-H1.5, H1(o) and H1t have
been isolated and sequenced. We have established expression patterns of these
genes in several tissues during postnatal development. For that analysis, RNase
protection assay rather than Northern blot hybridization was used, since the
sequences of these genes are highly similar and would cross-hybridize under
Northern blot conditions. Expression patterns of H1.1 to H1.5 and H1(o) were
determined in tissues of animals at days 5, 9 and 20 after birth and of adult
mice. In addition, RNA was analyzed in three mouse cell lines (NIH3T3, P19, TM4).
Transcription of the subtype genes H1.2 and H1.4 was found in all tissues and
cell lines studied. The most varied expression patterns were obtained with the
H1.1 subtype. H1.1 mRNA was found at high concentrations in thymus and spleen
throughout development and in testis beginning with a low expression in 5-day-old
animals and increasing levels in testis RNA from 9- and 20-day-old and adult
mice. H1(o) mRNA was found primarily in highly differentiated tissues with
concentrations decreasing from 5-day-old to adult animals.
PMID- 9655913
TI - Identification and sequencing of a cytochrome P450 gene cluster from
Bradyrhizobium japonicum.
AB - Sequencing of a region from Bradyrhizobium japonicum previously shown to encode
for cytochromes P450 revealed a cluster of three complete P450 genes (CYP112,
CYP114, and CYP117) plus a partial P450 gene fragment (CYP115P). Present also are
five additional open reading frames. The close positioning of the genes suggests
that they comprise an operon. Although the biochemical function of the gene
products is uncertain, the similarities to other genes suggests an operon
involved in terpenoid synthesis. ORF3 has similarity to a [3Fe-4S] ferredoxin
from Streptomyces griseolus. ORF4 has strong similarity to members of the short
chain alcohol dehydrogenase family, including sterol dehydrogenases from enteric
bacteria and to some plant 3-oxoacyl-(acyl carrier protein) reductases. ORF6 has
strong similarity to prenyl transferases, including dimethylallyltranstransferase
from Escherichia coli. ORF7 bears some similarity to plant genes for ent-kaurene
synthase (a precursor of gibberellins), and to bacterial squalene-hopene
cyclases. ORF8 has some similarity to a Streptomyces gene for synthesis of the
cyclic sesquiterpene pentalenene. The 5' end of the mRNA transcript is 38-39
nucleotides downstream from the center of a motif that bears sequence homology to
bacterial fnr promoters. A gus operon fusion to the promoter was expressed
anaerobically and symbiotically 6-10-fold greater than aerobically.
PMID- 9655914
TI - Theoretical studies on the electronic and energetic properties of the
aminopyrimidine part of thiamin diphosphate.
AB - Ab initio calculations on the HF-SCF 6-31g* level were performed on tautomers as
well as protonated and deprotonated species of thiamin. Aspects of the proton
relay function of the 4'-aminopyrimidine ring in the thiamin catalysis were
studied on model systems. The acidity of the 4'-amino group increases in the N1'
and N3' protonated thiamin systems. Starting from the 4'N deprotonated thiamin,
the calculated reaction coordinate of the ylide formation suggests the
cocatalytic function of the 4'-amino/imino group. Some structural, energetic, and
electronic properties of the model systems are discussed with respect to key
steps in the catalytic mechanism.
PMID- 9655915
TI - Structure-function relationships and flexible tetramer assembly in pyruvate
decarboxylase revealed by analysis of crystal structures.
AB - The crystal structures of pyruvate decarboxylase from the yeast Saccharomyces
uvarum and Saccharomyces cerevisiae have been determined at 2.4 and 2.3 A
resolution, respectively. These structures provide details about the protein fold
and domain assembly within subunits, about subunit assembly to form dimers and
about dimer assembly to form tetramers. They also provide a clear picture of the
active site centered on the thiamin diphosphate cofactor, and have allowed amino
acids critical for catalysis and involved in stabilization of the unusual
cofactor conformation to be identified. The structural information has enabled
identification of the site of allosteric activation to be centered on Cys-221,
and suggests that a six residue segment leading from the regulatory site to the
catalytic site may be involved in transmission of a binding signal. The
importance of several amino acids within this segment in the regulatory process,
as well as some involved in stabilizing and activating the cofactor has been
confirmed by analyzing the behavior of recombinant enzymes with single point
mutations introduced at these sites. Additional structures have been determined
for pyruvate decarboxylase in multiple crystal forms, some of which were obtained
from crystals grown with known allosteric activators present in the media.
Currently four distinct types of tetramers have been observed, with each showing
a different mode of association of dimers to form the tetramers. In some of the
cases involving the presence of allosteric activators drastic changes in the mode
of dimer assembly to form tetramers is seen.
PMID- 9655916
TI - Differential requirements for basic amino acids in transcription factor IIIA-5S
gene interaction.
AB - Basic amino acids Arg, Lys, and His in the Cys2His2 zinc fingers of transcription
factor IIIA (TFIIIA) potentially have important roles in factor binding to the
extended internal control region (ICR) of the 5S ribosomal gene. Conserved and
non-conserved basic residues in the N-terminal fingers I, II, III and the more C
terminal fingers V and IX were analyzed by site-directed mutagenesis and DNase I
protection in order to assess their individual requirement in the DNA-binding
mechanism. In the DNA recognition helix of finger II, the conserved Arg at
position 62 (N-terminal side of the first zinc-coordinating histidine) was
changed to a Leu or Gln. Both the R62L and R62Q mutations inhibited Xenopus
TFIIIA-dependent DNase I footprinting along the entire 5S gene ICR. When His-58
(non-conserved basic residue with DNA-binding potential in the same helical
region) was changed to a Gln, the mutated protein was able to protect the ICR
from DNase I digestion. Therefore, Arg-62 is individually required for TFIIIA
binding over the entire ICR whereas His-58 is not. Fingers V and IX have
conserved Arg residues in positions identical to Arg-62 in finger II (Arg-154 in
finger V and Arg-271 in finger IX). When these residues were changed to Leu and
Ile respectively, TFIIIA-dependent DNase I protection was observed along the
entire 5S gene ICR. These results indicate differing DNA-binding mechanisms by
the N-terminal fingers versus the C-terminal fingers at the level of individual
amino acid-nucleotide interactions. In the N-terminal finger I, the conserved Lys
at position 11 outside the recognition helix and a conserved hydrophobic Trp at
position 28 within the helix were changed to an Ala and Ser respectively. The
K11A change inhibited TFIIIA-dependent DNase I protection to a much greater
extent than the W28S change.
PMID- 9655917
TI - Cloning and sequencing of the cDNA for an RNA-binding protein from the Mexican
axolotl: binding affinity of the in vitro synthesized protein.
AB - A full length cDNA for an RNA-binding protein (axolotl RBP) with consensus
sequence (RNP-CS) from the Mexican axolotl, Ambystoma mexicanum, has been cloned
from a subtraction library. In vitro translation with synthetic mRNA and
subsequent hybrid-arrested translation with a specific antisense oligonucleotide
confirms that the axolotl RBP cDNA encodes an approx. 16 kDa polypeptide.
Computer-assisted analyses revealed amino acid similarities of 58-60% to various
RNA-binding proteins and a 90 amino acid region at the amino-terminal end
constituting the putative RNA-binding domain (RNP-CS) with two highly conserved
motifs, RNP2 and RNP1. Phylogenetic analysis suggests that the putative RNA
binding protein from axolotl is unique. A binding assay with radiolabeled axolotl
RBP showed that this RNA-binding protein bound strongly with poly(A) and to a
lesser degree with poly(U), but not at all with poly(G), poly(C), or DNA.
PMID- 9655918
TI - Subunit structure, function and organisation of pyruvate decarboxylases from
various organisms.
AB - The nature of the environment of macromolecules influences and determines the
state of their overall structure and the extent of binding of specific
(cofactors, substrates) or unspecific ligands. How these interactions between
enzyme molecules and ligands influence their quaternary structures and, in this
way, the realisation of high catalytic activity will be discussed here for the
enzyme pyruvate decarboxylase from various organisms: brewer's yeast, brewer's
yeast strain, recombinant wild type and site-specific mutants of Saccharomyces
cerevisiae, the recombinant wild type of the bacterium Zymomonas mobilis and
germinating seeds of the plant Pisum sativum from a structural point of view
including both high resolution models from crystal structure analysis and low
resolution models from small angle X-ray solution scattering with synchrotron
radiation.
PMID- 9655919
TI - Superinduction of interleukin-6 mRNA in lung epithelial H292 cells depends on
transiently increased C/EBP activity and durable increased mRNA stability.
AB - Restriction of eukaryotic protein synthesis affects the regulation of some
transiently expressed gene transcripts resulting in their superinduction. We
determined the transcriptional and post-transcriptional processes implicated in
IL-6 mRNA superinduction in a human lung-derived epithelial cell line H292, and
their kinetics in the absence and presence of an exogenous stimulus, tumor
necrosis factor-alpha (TNF-alpha). Cycloheximide (CHI) at 10 microg/ml, which
inhibited protein synthesis for 80%, caused a 80-fold induction of IL-6 mRNA
level which was due predominantly to a stabilization of IL-6 mRNA (20-fold) early
on. Employing transient transfection protocols we noted a small positive effect
of CHI on transcription, mediated by the proximal and the distal C/EBP sites of
the IL-6 promoter and paralleled by an increased C/EBP DNA-binding activity,
similar to that found for exposure to TNF-alpha alone. TNF-alpha and CHI
synergized on IL-6 mRNA expression (200-fold increase) which was due to an
increased transcription, corresponding to a further increased C/EBP DNA-binding
activity. However, the effect of CHI on IL-6 gene transcription was transient, in
support of the need for ongoing protein synthesis for C/EBP activity. These
findings indicate that IL-6 mRNA superinduction, at least in H292 cells, is
regulated predominantly by modulating the repressive system that ensures a rapid
degradation of IL-6 mRNA.
PMID- 9655920
TI - 1,25-Dihydroxyvitamin D3 inhibition of col1a1 promoter expression in calvariae
from neonatal transgenic mice.
AB - We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on organ cultures
of transgenic mouse calvariae containing segments of the Col1a1 promoter
extending to -3518, -2297, -1997, -1794, -1763, and -1719 bp upstream of the
transcription start site fused to the chloramphenicol acetyltransferase (CAT)
reporter gene. 1,25(OH)2D3 had a dose-dependent inhibitory effect on the
expression of the -3518 bp promoter construct (ColCAT3.6), with maximal
inhibition of about 50% at 10 nM. This level of inhibition was consistent with
the previously observed effect on the endogenous Col1a1 gene in bone cell models.
All of the shorter constructs were also inhibited by 10 nM 1,25(OH)2D3,
suggesting that the sequences required for 1, 25(OH)2D3 inhibition are downstream
of -1719 bp. The inhibitory effect of 1,25(OH)2D3 on transgene mRNA was
maintained in the presence of the protein synthesis inhibitor cycloheximide,
suggesting that the inhibitory effect on Col1a1 gene transcription does not
require de novo protein synthesis. We also examined the in vivo effect of
1,25(OH)2D3 treatment of transgenic mice on ColCAT activity, and found that 48 h
treatment caused a dose-dependent inhibition of CAT activity in calvariae
comparable to that observed in organ cultures. In conclusion, we demonstrated
that 1,25(OH)2D3 inhibits Col1A1 promoter activity in transgenic mouse calvariae,
both in vivo and in vitro. The results indicate that there is a 1, 25(OH)2D3
responsive element downstream of -1719 bp. The inhibitory effect does not require
new protein synthesis.
PMID- 9655921
TI - Regulation of thiamin diphosphate-dependent 2-oxo acid decarboxylases by
substrate and thiamin diphosphate.Mg(II) - evidence for tertiary and quaternary
interactions.
AB - The regulatory mechanism of substrate activation in yeast pyruvate decarboxylase
is triggered by the interaction of pyruvic acid with C221 located on the beta
domain at >20 A from the thiamin diphosphate (ThDP). To trace the putative
information transfer pathway, substitutions were made at H92 on the alpha domain,
across the domain divide from C221, at E91, next to H92 and hydrogen bonded to
W412, the latter being intimately involved in the coenzyme binding locus.
Additional substitutions were made at D28, E51, H114, H115, I415 and E477, all
near the active center. The pH-dependent steady-state kinetic parameters,
including the Hill coefficient, provide useful insight to this effort. In
addition to C221, the residues H92, E91, E51 and H114 and H115 together appear to
have a critical impact on the Hill coefficient, providing a pathway for
information transfer. To study the activation by ThDP.Mg(II), variants at G231
(of the conserved GDG triplet) and at N258 and C259 (all three being part of the
putative ThDP fold) of the E1 component of the Escherichia coli pyruvate
dehydrogenase multienzyme complex were studied. Kinetic and spectroscopic
evidence suggests that the Mg(II) ligands are very important to activation of the
enzymes by cofactors.
PMID- 9655922
TI - Identification of heavy metal induced changes in the expression patterns of the
translationally controlled tumour protein (TCTP) in the earthworm Lumbricus
rubellus1.
AB - Heavy metal contaminated soils are assessed for specific human health and
ecological risk by governmental regulatory agencies utilizing the abundant soil
invertebrate, the earthworm, in a biomonitoring process. Fingerprinting the
molecular genetic responses resulting from heavy metal exposure facilitates the
identification of biomarkers for assessing the impact of such pollution on
individual organisms. This paper reports the identification of a novel
translationally controlled tumour protein (TCTP) in the earthworm Lumbricus
rubellus. In addition to the standard molecular biological technique of
differential Southern blotting, a fully quantitative approach (fluorescent
microvolume PCR) was performed to assess the specific expression profiles of TCTP
in earthworms exposed to different heavy metal regimes. After normalizing with
actin as an invariant control, the results showed that TCTP was upregulated by at
least a factor of 4 in the population originating from a Pb/Zn/Cd polluted mine,
compared to an unpolluted control population. An even more pronounced increase
was identified in earthworms native to a Cu polluted mine, where TCTP increased
335-fold. TCTP copies in earthworms exposed to artificial soil with a single
stressor (Cd) were 14 times higher than in the appropriate control earthworms
(maintained on artificial soil without Cd). The data presented are novel in two
ways: first, they provide evidence for an upregulation that is induced by heavy
metals (especially copper); second, they show that TCTP can also be under
transcriptional control, therefore upregulation is not limited to translational
modifications as TCTP's nomenclature suggests.
PMID- 9655923
TI - HIV-1 Gag binds specifically to RNA stem-loops in the 5' leader sequence.
AB - GST-Gag(p55) binds specifically to HIV-1 RNA sequences 1-406, in vitro, with a Kd
of about 50 nM. This RNA transcript contains a number of stem loop (SL)
structures. The binding is due to the Gag moiety of the fusion protein, not GST.
There is a high affinity binding site for Gag in an RNA containing nucleotides
325-362. SL4 is predicted by both biochemical studies and computer folding to be
located between nucleotides 335 and 358. An RNA transcript ending at nucleotide
335 does not bind Gag. The deletion of nucleotides 334-358 from HIV-1 RNAs does
not affect Gag binding. Digestions with RNase V1 and T1 show that nucleotides 297
300 in SL2, 310, 312, 313, 315, 317, 318, 325 in SL3, and 342 and 343 in SL4 are
protected in the presence of Gag. The cleavage of nucleotides 348-351 in SL4 by
RNAse V1 is enhanced by Gag binding. At least two Gag binding sites are therefore
located in the leader RNA. Those located 5' of nucleotide 335 require the
presence of additional 3' sequences.
PMID- 9655924
TI - Application of alpha-keto acid decarboxylases in biotransformations.
AB - The advantages of using enzymes in the synthesis of organic compounds relate to
their versatility, high reaction rates, and regio- and stereospecificity and the
relatively mild reaction conditions involved. Stereospecificity is especially
important in the synthesis of bioactive molecules, as only one of the
enantiomeric forms usually manifests bioactivity, whereas the other is often
toxic. Although enzymes which catalyze asymmetric carbon-carbon bond formation
are of great importance in bioorganic chemistry, only a few examples are known
for thiamin diphosphate (ThDP)-dependent enzymes, whereas transformations using
e.g. aldolases, lipases and lyases are well documented already. The present
review surveys recent work on the application of pyruvate decarboxylase and
benzoylformate decarboxylase in organic synthesis. These enzymes catalyze the
synthesis of chiral alpha-hydroxy ketones which are versatile building blocks for
organic and pharmaceutical chemistry. Besides the substrate spectra of both
enzymes amino acid residues relevant for substrate specificity and
enantioselectivity of pyruvate decarboxylase have been investigated by site
directed mutagenesis.
PMID- 9655925
TI - Minimum CAG repeat in the human calmodulin-1 gene 5' untranslated region is
required for full expression.
AB - The human calmodulin-1 gene (hCALM1) contains a (CAG)7 repeat in its 5'
untranslated region (5'-UTR). We found this repeat to be stable and
nonpolymorphic in the human population. To determine whether the repeat region
affects hCALM1 expression and whether repeat expansions to numbers known to be
associated with disease in other genes may alter expression, we tested luciferase
reporter genes driven by the hCALM1 promoter and 5'-UTR containing 0, 7 (wild
type), 20, and 45 CAG repeats in human NT2/D1 teratoma cells. Interestingly, the
repeat deletion, (CAG)0, decreased expression by 45%, while repeat expansions to
(CAG)20 and (CAG)45, or the insertion of a scrambled (C,A,G)7 sequence did not
alter gene expression. These data indicate (1) that the endogenous repeat element
is required for full expression of hCALM1, and (2) that some triplet repeat
expansions in the 5'-UTR of protein-coding genes may be well tolerated and even
optimize gene expression.
PMID- 9655926
TI - Kzf1 - a novel KRAB zinc finger protein encoding gene expressed during rat
spermatogenesis.
AB - Two novel KRAB (Kruppel associated box) type zinc finger protein encoding cDNAs,
named Kzf1 and Kzf2 (Kzf for KRAB zinc finger), were identified by screening of a
rat embryonic brain cDNA library with a human ZNF91 KRAB probe. Kzf1 and Kzf2
encode proteins with an amino-terminal KRAB domain and a carboxy-terminal zinc
finger cluster containing 9 and 13 zinc finger units, respectively. While Kzf2
appears to be ubiquitously expressed, Kzf1 is preferentially expressed in the
testis. Within the testis, Kzf1 mRNA is restricted to germ cells. The Kzf1
protein exhibits DNA binding activity and its KRAB domain can function as a
repressor module in transcription. Using somatic cell hybrid analysis, the Kzf1
gene was mapped to chromosome 6.
PMID- 9655927
TI - Structure and properties of pyruvate decarboxylase and site-directed mutagenesis
of the Zymomonas mobilis enzyme.
AB - Pyruvate decarboxylase (EC 4.1.1.1) is a thiamin diphosphate-dependent enzyme
that catalyzes the penultimate step in alcohol fermentation. The enzyme is widely
distributed in plants and fungi but is rare in prokaryotes and absent in animals.
Here we review its structure and properties with particular emphasis on how site
directed mutagenesis of the enzyme from Zymomonas mobilis has assisted us to
understand the function of critical residues.
PMID- 9655928
TI - Cloning and sequencing of a novel Na+/H+ antiporter gene from Pseudomonas
aeruginosa.
AB - We cloned a gene for Na+/H+ antiporter from chromosomal DNA of Pseudomonas
aeruginosa. Introduction of the gene into host Escherichia coli mutant cells
lacking all of the major Na+/H+ antiporters enabled the cells to grow in the
presence of 0.2 M NaCl, although the original host cells could not. Membrane
vesicles prepared from cells of the transformant possessing the cloned gene
showed Na+/H+ antiport activity. As a result of DNA sequencing, we found one open
reading frame (nhaP). The deduced amino acid sequence suggests that the Na+/H+
antiporter (NhaP) of P. aeruginosa consists of 424 amino acid residues with
molecular mass of 45486 Da, and hydropathy analysis suggested the presence of 12
putative transmembrane domains. We found no bacterial Na+/H+ antiporter which
showed significant sequence similarity with the NhaP in the protein sequence
database. The NhaP showed partial sequence similarity with animal Na+/H+
exchangers. Thus, the NhaP of P. aeruginosa is unique among bacterial
antiporters.
PMID- 9655929
TI - Up-regulated expression of murine Mcl1/EAT, a bcl-2 related gene, in the early
stage of differentiation of murine embryonal carcinoma cells and embryonic stem
cells.
AB - We have cloned a murine homologue of the human Mcl1/EAT gene, a Bcl-2 related
gene. Sequence analysis revealed that murine Mcl1/EAT (mMcl1/EAT) has three Bcl-2
homology domains, two PEST sequences, and immediate response boxes (IRB). The
presence of IRB indicates that mMcl1/EAT is an immediate-early gene. mMcl1/EAT
increases dramatically with exposure to retinoic acid in murine embryonal
carcinoma cell lines (F9 and PCC3) as well as embryonic stem cells, both of which
are models of early embryogenesis.
PMID- 9655930
TI - The pyruvate dehydrogenase complex from thermophilic organisms: thermal stability
and re-association from the enzyme components.
AB - Examples of pyruvate dehydrogenase complexes, and of its probable precursors, the
pyruvate ferredoxin oxidoreductases, both isolated from thermophilic organisms,
are described. The pyruvate ferredoxin oxidoreductases are mostly characterized
from thermophilic archaea like Sulfolobus solfataricus and Pyrococcus furiosus.
They retain their catalytic activity up to 60 and 90 degreesC, respectively.
Characteristic for the thermophilic nature is a biphasic temperature behavior,
reflecting a more stable low temperature and a metastable high temperature form.
Another feature is the strong binding of the cofactor thiamin diphosphate.
Detailed analysis of thermostable pyruvate dehydrogenase complexes so far only
exist for the enzymes from Bacillus stearothermophilus and Thermus flavus. In
most respects, especially in the structural features, the enzyme complex from B.
stearothermophilus resembles its mesophilic counterparts and only an elevated
temperature maximum for the catalytic activity reveals the thermophilic nature.
In contrast to this, the more thermostable enzyme complex from T. flavus shows a
quite distinct behavior. One single protein chain (Mr=100 kDa) instead of an
alpha2beta2 aggregate was found for the pyruvate dehydrogenase (E1) subunits of
this enzyme complex. Its catalytic activity is controlled by allosteric
regulation, while the enzyme complex from B. stearothermophilus shows no such
regulation. Reversible phosphorylation as a regulatory principle of pyruvate
dehydrogenase complexes from higher organisms does not take place in the
thermophilic enzyme complexes. The overall activity of the enzyme complex from B.
stearothermophilus remains stable at 60 degreesC for 50 min while that from T.
flavus is active up to 83 degreesC. Thermophilic pyruvate dehydrogenase complexes
do not spontaneously renature from their separated enzyme components. However,
chaperonins from Thermus thermophilus stimulate the reactivation of the enzyme
complex from T. flavus.
PMID- 9655931
TI - Specific expression of an expansin gene during elongation of cotton fibres.
AB - A differential screening experiment resulted in the isolation of a full-length
cDNA clone encoding an expansin from cotton fibres. Nucleotide and derived amino
acid sequence data showed that pGhEX1 encodes an expansin of 258 amino acids,
with an N-terminal signal peptide. Northern blot analysis showed that the
corresponding transcript is abundant in cotton fibre cells but absent in all
other tissues tested, and that the gene is developmentally regulated during fibre
elongation.
PMID- 9655932
TI - Isolation and characterization of cDNA encoding rat heart type acetyl-CoA
carboxylase.
AB - We isolated and characterized cDNA clones encoding the entire open reading frame
(ORF) of a protein consisting of 2456 amino acids with a molecular mass of 276069
Da from rat heart. As the deduced amino acid sequence showed 85% homology with
that of human type 2 acetyl-CoA carboxylase (ACC2), we concluded that the cDNA
clones encode rat heart type ACC2. Using the identified cDNA fragments and the
reported cDNA fragment of rat type 1 ACC (ACC1), we determined the steady state
transcript levels of ACC1 and ACC2 in various rat tissues quantitatively by
Northern blot analysis. The transcript level of ACC2 was high in heart, skeletal
muscle and brown adipose tissue, which require high energy and mainly metabolize
fatty acids, whereas that of ACC1 was high in white adipose tissue, which stores
fatty acids.
PMID- 9655933
TI - The pyruvate dehydrogenase multi-enzyme complex from Gram-negative bacteria.
AB - Pyruvate dehydrogenase multi-enzyme complexes from Gram-negative bacteria
consists of three enzymes, pyruvate dehydrogenase/decarboxylase (E1p),
dihydrolipoyl acetyltransferase (E2p) and dihydrolipoyl dehydrogenase (E3). The
acetyltransferase harbors all properties required for multi-enzyme catalysis: it
forms a large core of 24 subunits, it contains multiple binding sites for the E1p
and E3 components, the acetyltransferase catalytic site and mobile substrate
carrying lipoyl domains that visit the active sites. Today, the Azotobacter
vinelandii complex is the best understood oxo acid dehydrogenase complex with
respect to structural details. A description of multi-enzyme catalysis starts
with the structural and catalytic properties of the individual components of the
complex. Integration of the individual properties is obtained by a description of
how the many copies of the individual enzymes are arranged in the complex and how
the lipoyl domains couple the activities of the respective active sites by way of
flexible linkers. These latter aspects are the most difficult to study and future
research need to be aimed at these properties.
PMID- 9655934
TI - Sequence analysis and expression of a novel mouse homolog of Escherichia coli
recA gene.
AB - Escherichia coli recA and its yeast homologs RAD51 and DMC1 play crucial roles in
mitotic and/or meiotic recombination and in repair of double-strand DNA breaks.
We have identified a murine novel recA-like gene (MmTRAD). The predicted 329
amino acid protein showed significant homology to mouse Rec2, Rad51, Dmc1 (or
Lim15) and E. coli RecA. Northern blot analysis revealed that MmTRAD was
ubiquitously transcribed in various tissues.
PMID- 9655935
TI - Molecular cloning of a gene encoding phospholipase D from the pathogenic and
dimorphic fungus, Candida albicans.
AB - A phospholipase D gene (CaPLD) has been cloned from the Candida albicans genomic
DNA library. The CaPLD is a member of a highly conserved gene family of PLD and
has the highest homology to Saccharomyces cerevisiae PLD (SPO14) with an overall
homology of 42%. Phylogenetic analysis indicated that fungus PLDs including CaPLD
composed one of the three clusters of PLD genes.
PMID- 9655936
TI - The human noradrenaline transporter gene contains multiple polyadenylation sites
and two alternatively spliced C-terminal exons.
AB - Sequencing downstream of the C-terminal exon 14 of the human noradrenaline
transporter (hNAT) gene reveals 5 consensus polyadenylation signals, several
adenylate/uridylate-rich elements (AREs) and a new C-terminal exon, designated as
exon 15. The tandemly arranged polyadenylation sites are in good conformity with
the 3.6- and 5.8-kb hNAT mRNA transcripts. Expression of the alternatively
spliced C-terminal exon 15 is shown by RT-PCR. This alternative splicing event
proposes additional hNAT mRNA species of 2.4-3 kb in size. Corresponding NAT
transcripts are found by Northern analysis of human SKN and rat PC12 cell RNA.
Sequence comparison of the hNAT gene to two bovine NAT cDNAs shows the
interspecies conservation of this alternative splicing event, the close
relationship of human and bovine NAT genes, and implicates a functional role for
the transporters C-terminal domain.
PMID- 9655937
TI - Gene and subunit organization of bacterial pyruvate dehydrogenase complexes.
AB - Pyruvate dehydrogenase complexes of bacterial origin are compared with respect to
subunit composition, organization of the corresponding genes, and the number and
location of lipoyl domains. Special attention is given to two unusual examples of
pyruvate dehydrogenase complexes, formed by Zymomonas mobilis and Thiobacillus
ferrooxidans.
PMID- 9655938
TI - Molecular cloning and characterisation of a mouse gene encoding an isoform of the
neuronal cyclin-dependent kinase 5 (CDK5) activator.
AB - We have isolated and characterised the mouse gene for the p39 activator,
designated p39is, which encodes a protein of 369 amino acids. The mouse p39
protein exhibits 95% amino acid identity to a previously characterised human p39
cDNA and the novel gene sequence corresponds to a single genomic locus in mouse.
The p39is mRNA is highly expressed in the mouse central nervous system.
PMID- 9655939
TI - Cloning, structure, chromosomal localization and promoter analysis of human 2
oxoglutarate dehydrogenase gene.
AB - Human 2-oxoglutarate dehydrogenase (OGDH) is an E1-component of the OGDH multi
enzyme complex and catalyzes both the ThDP-dependent decarboxylation of 2
oxoglutarate and the subsequent reductive succinylation of the lipoyl moiety
which is covalently bound to the E2 component, dihydrolipoamide
succinyltransferase. The cDNA and genomic DNA encoding human OGDH has been cloned
and sequenced. The cDNA contains a 3006-bp open reading frame encoding a 40-amino
acid leader peptide and a 962-amino acid mature OGDH protein (Mr=108878). The
gene contains 22 exons spanning approximately 85 kb. The putative ThDP-binding
sequence motif is identified in both DNAs. The gene is localized to chromosome 7
at p13-p14 by fluorescence in situ hybridization. With the TATA- and CAAT-less 5'
flanking region (wild type, -3276/+212) of the OGDH gene-luciferase reporter
vector construct and its nested deletion or linker-scanning mutant constructs the
transient reporter expression assays in BHK-21 cells reveal the existence of two
10-bp cis-acting elements (-53/-44 and -33/-24) and two trans-acting elements (
536/-496 and -93/-84). A nuclear factor that binds to the region from -63 to -24
including two cis-acting elements.
PMID- 9655940
TI - cDNA cloning of mouse BLM gene, the homologue to human Bloom's syndrome gene,
which is highly expressed in the testis at the mRNA level.
AB - We cloned a cDNA encoding the mouse homologue to human Bloom's syndrome gene
(BLM). The deduced amino acid sequence of mouse Blm showed 76% identity to the
human sequence with very high homology in seven consecutive domains
characteristic of DNA and RNA helicases. The expression of mBLM mRNA was examined
in various tissues. Extremely high expression was observed in the testis as
compared with other tissues. The mBLM mRNA level in the testis began to increase
12-14 days after birth, corresponding to the appearance of cells in the pachytene
phase.
PMID- 9655941
TI - Alternative splicing and structure of the human erythroid dematin gene.
AB - Human erythroid dematin is a cytoskeletal protein capable of bundling actin
filaments in vitro. The carboxyl terminal domain of dematin is homologous to the
headpiece domain of villin, an actin-binding protein of the brush border
cytoskeleton. Here we report the complete structure of the dematin gene located
on human chromosome 8p21.1, a region frequently deleted in prostate cancer. The
dematin gene is composed of 15 exons spanning approximately 15 kb. We also report
two novel isoforms of dematin derived from alternative splicing of the dematin
gene in the brain.
PMID- 9655942
TI - Cloning, structural organization and tissue-specific expression of the rabbit
transferrin gene.
AB - We cloned the rabbit transferrin (rTf) cDNA and gene, and quantified the
expression of the rTf gene at the RNA level in various organs. The tissue
specific pattern of expression of rTf gene is different to those in other
species, with a high expression in mammary gland and kidney. The exon/intron
structure of the rTf gene (17 exons/16 introns) is similar to those of
transferrins from other species. The sequence of the rTf cDNA already published
is corrected and lengthened in the 5' region, and a likely polymorphism is
documented.
PMID- 9655943
TI - Crystallography and mutagenesis of transketolase: mechanistic implications for
enzymatic thiamin catalysis.
AB - The ThDP dependent enzyme transketolase is a convenient model system to study
enzymatic thiamin catalysis. Crystallographic studies of the enzyme have
identified the ThDP binding fold, the V-conformation of ThDP as the relevant
conformation in enzymatic catalysis and details of enzyme-substrate interactions.
Based on this structural information, the function of various active site
residues in substrate binding and catalysis has been probed by site-directed
mutagenesis.
PMID- 9655944
TI - Cloning and analysis of a transcript derived from two contiguous genes of the
cathelicidin family.
AB - Bac4 is a bovine cathelicidin gene contiguous to another member of this family
named Bac7. Although mutations in the sequence suggested that Bac4 gene might be
non-functional, primers based on Bac4 specific sequences allowed amplification of
a 900 bp cDNA. The transcript comprises the sequences of exons 1, 2 and 3 of
Bac7, and of exons 2, 3 and 4 of Bac4 gene and may result from a weak termination
control of the transcription of the upstream Bac7 gene.
PMID- 9655945
TI - Biochemical and genetic characterization of three molybdenum cofactor
hydroxylases in Arabidopsis thaliana.
AB - Aldehyde oxidases and xanthine dehydrogenases/oxidases belong to the molybdenum
cofactor dependent hydroxylase class of enzymes. Zymograms show that Arabidopsis
thaliana has at least three different aldehyde oxidases and one xanthine oxidase.
Three different cDNA clones encoding putative aldehyde oxidases (AtAO1, 2, 3)
were isolated. An aldehyde oxidase is the last step in abscisic acid (ABA)
biosynthesis. AtAO1 is mainly expressed in seeds and roots which might reflect
that it is involved in ABA biosynthesis.
PMID- 9655947
TI - [Protein phosphatase as a partner of protein kinase].
PMID- 9655946
TI - Biosynthesis of 2-aceto-2-hydroxy acids: acetolactate synthases and
acetohydroxyacid synthases.
AB - Two groups of enzymes are classified as acetolactate synthase (EC 4. 1.3.18).
This review deals chiefly with the FAD-dependent, biosynthetic enzymes which
readily catalyze the formation of acetohydroxybutyrate from pyruvate and 2
oxobutyrate, as well as of acetolactate from two molecules of pyruvate (the
ALS/AHAS group). These enzymes are generally susceptible to inhibition by one or
more of the branched-chain amino acids which are ultimate products of the
acetohydroxyacids, as well as by several classes of herbicides (sulfonylureas,
imidazolinones and others). Some ALS/AHASs also catalyze the (non-physiological)
oxidative decarboxylation of pyruvate, leading to peracetic acid; the possible
relationship of this process to oxygen toxicity is considered. The bacterial
ALS/AHAS which have been well characterized consist of catalytic subunits (around
60 kDa) and smaller regulatory subunits in an alpha2beta2 structure. In the case
of Escherichia coli isozyme III, assembly and dissociation of the holoenzyme has
been studied. The quaternary structure of the eukaryotic enzymes is less clear
and in plants and yeast only catalytic polypeptides (homologous to those of
bacteria) have been clearly identified. The presence of regulatory polypeptides
in these organisms cannot be ruled out, however, and genes which encode putative
ALS/AHAS regulatory subunits have been identified in some cases. A consensus
sequence can be constructed from the 21 sequences which have been shown
experimentally to represent ALS/AHAS catalytic polypeptides. Many other sequences
fit this consensus, but some genes identified as putative 'acetolactate synthase
genes' are almost certainly not ALS/AHAS. The solution of the crystal structures
of several thiamin diphosphate (ThDP)-dependent enzymes which are homologous to
ALS/AHAS, together with the availability of many amino acid sequences for the
latter enzymes, has made it possible for two laboratories to propose similar,
reasonable models for a dimer of catalytic subunits of an ALS/AHAS. A number of
characteristics of these enzymes can now be better understood on the basis of
such models: the nature of the herbicide binding site, the structural role of FAD
and the binding of ThDP-Mg2+. The models are also guides for experimental testing
of ideas concerning structure-function relationships in these enzymes, e.g. the
nature of the substrate recognition site. Among the important remaining questions
is how the enzyme suppresses alternative reactions of the intrinsically reactive
hydroxyethylThDP enamine formed by the decarboxylation of the first substrate
molecule and specifically promotes its condensation with 2-oxobutyrate or
pyruvate.
PMID- 9655948
TI - [Protein serine/threonine phosphatases].
PMID- 9655949
TI - [Structural biology of PP1].
PMID- 9655950
TI - [The structure and regulatory mechanisms of protein phosphatase 2A].
PMID- 9655951
TI - [The structure and regulation of calcineurin].
PMID- 9655952
TI - [Structure and function of mammalian protein phosphatase 2C].
PMID- 9655953
TI - [Neoplastic alterations of protein phosphatases and their significance].
PMID- 9655954
TI - [Role of myosin phosphatase in smooth muscle contraction].
PMID- 9655955
TI - [Control of M-phase progression by protein phosphatases].
PMID- 9655956
TI - [Regulation of functions of intermediate filaments by protein phosphatases].
PMID- 9655957
TI - [Dephosphorylation of cytoskeletal proteins: phosphorylation and
dephosphorylation of microtubule proteins].
PMID- 9655958
TI - [Protein phosphatase 2A in the control of cell function].
PMID- 9655959
TI - [Calcineurin-mediated signal transduction pathways in yeast].
PMID- 9655960
TI - [Possible involvement of protein Ser/Thr phosphatase in leukemic cell
differentiation and proliferation].
PMID- 9655961
TI - [Physiological role of calcineurin in central nervous system].
PMID- 9655962
TI - [The role of calcineurin in the regulation of transcription factors].
PMID- 9655963
TI - [Negative regulation of the stress-activated protein kinase pathway by protein
phosphatases].
PMID- 9655964
TI - [Neuronal plasticity and protein phosphatase].
PMID- 9655965
TI - [Regulatory proteins of type 1 protein phosphatase].
PMID- 9655966
TI - [Total synthesis and conformational analysis of inhibitors].
PMID- 9655967
TI - [Naturally occurring toxins with specific inhibitory activity against protein
serine/threonine phosphatases 1 and 2A].
PMID- 9655968
TI - [Tumor promotion by inhibitors of protein phosphatase 1 and 2A].
PMID- 9655969
TI - [Genomic instability induced by a protein phosphatase inhibitor okadaic acid].
PMID- 9655970
TI - [Multiple actions of tacrolimus and cyclosporin A as specific inhibitors of
calcineurin].
PMID- 9655971
TI - [Structure and function of protein tyrosine phosphatases].
PMID- 9655972
TI - [Role of tyrosine phosphatases in neuronal differentiation].
PMID- 9655973
TI - [The roles of protein tyrosine phosphatases during hematopoietic progenitor cell
development and differentiation].
PMID- 9655974
TI - [Involvement of PTP-U2 in terminal differentiation and apoptosis of leukemia
cells].
PMID- 9655975
TI - [Structure, expression and functions of receptor-type protein tyrosine
phosphatase RPTP-BK in central nervous system].
PMID- 9655976
TI - [Regulation of lymphocyte signal transduction by protein tyrosine phosphatases].
PMID- 9655977
TI - [Protein tyrosine phosphatases in the signal transduction pathways of cell
adhesion].
PMID- 9655978
TI - [Involvement of protein tyrosine phosphatases in cancer development].
PMID- 9655979
TI - [FAP-1: a protein tyrosine phosphatase that is involved in Fas-mediated
apoptosis].
PMID- 9655980
TI - [Roles of protein-tyrosine phosphatases in insulin-mediated signal transduction
system].
PMID- 9655981
TI - [Protein phosphatase studies that I experienced].
PMID- 9655982
TI - [Basic concepts in insurance medicine. Life insurance. Positive and negative
performance picture].
PMID- 9655983
TI - [State control of human existence: being free instead of freedom].
PMID- 9655984
TI - [Possibilities and risks of genetic diagnosis].
AB - In the recent past, cytogenetic and molecular genetic methods led to an enormous
increase in knowledge on genetic information. It reveals a correlation between
the genetic information and the phenotype of an individual. Therefore, new
starting points concerning the origin of diseases arise. A new nosology will
develop. It will force researchers to emphasize more and more on the contribution
of the--disturbed--genetic information system to the development of diseases.
They will routinely carry out genome analyses on the following four already
established levels: 1. phenotype level, 2. biochemical level, 3. chromosomal
level, 4. molecular genetic level. Practicians mustn't close their mind to these
new possibilities and methods: The three classical tasks of medicine--diagnosis,
prevention and therapy--will be supplemented considerably by an earlier
(presymptomatic) and more precise diagnosis that is furthermore independent of
the organ. Moreover, there is the increasing possibility to predict the risk to
develop a disease for descendants in certain partnerships more precisely and, if
necessary, to diagnose prenatally. From the medical point of view, these advances
are predominantly positive and to the patient's benefit. But it is pointed out
that the diagnostic progress also raises new problems which were previously
unknown. The answers will have to be given by society as a whole.
PMID- 9655985
TI - [AIDS and life insurance in Germany. 10 years successful risk management].
AB - The introduction of AIDS specific measures by the German life assurance industry
in 1988 was an important step towards prevention of adverse selection by the well
known risk groups. In retrospect one can state that in the eighties there was a
tendency of risk groups for inappropriately high insurance coverage. This could
be curtailed with the introduction of a question as to a positive HIV test in
each proposal form and a mandatory HIV test for every policy exceeding DM
250,000. These tendencies could very nicely be demonstrated by studies of own
AIDS cases. The claims for death and disability benefits because of AIDS are as
of now compared to the total claims of minor importance.
PMID- 9655986
TI - [MCS, CFS, FMS, SBS and other "modern" illnesses].
AB - Common "environmental illnesses" are outlined with respect to their history and
case definition. As no objective diagnostic criteria are available, these
diagnoses may only be applied after sufficient exclusion of other known diseases.
Profound knowledge regarding the etiology of these conditions is still lacking,
and scientifically based somatic concepts for their therapy do not exist. Thus
there is room for a multitude of unvalidated methods for diagnosis and therapy,
and alleged causes are readily offered. The psychologic and economic consequences
for the affected individuals are sometimes deleterious, the costs are a growing
public concern. Proposals are made for the management of cases of suspected
environmental illness.
PMID- 9655987
TI - [Psychosomatic aspects of sudden deafness].
AB - In a psychosomatic point of view in an overwhelming number of cases sudden
deafness is a "response" to strain, which consciously or unconsciously is not
assessed as tolerable. Special personal or situational circumstances seem to
occur frequently, besides of psychomental strain above all high pressure of
responsibility in situations of care, high sensibility and inhibition to show
overt aggressive behaviour, which is suppressed by guilt feelings. These findings
are used to develop a first idealtypic psychopathogenetic model of sudden
deafness. Detecting and talking about the individual psychosocial strain of the
patient is very important in the management of the disease and the social
medicine assessments, especially in determining duration of disablement and
estimating grade of disability (GdB) in the case of persistent decrease of
hearing and tinnitus.
PMID- 9655988
TI - [Erroneous arguments on remaining risk in medical malpractice].
PMID- 9655989
TI - A gentamicin order form improves its use.
AB - To assess the effects of implementing a standardized order form on the
prescribing and monitoring of gentamicin sulfate at a nonteaching Veterans
Affairs Medical Center, we prospectively evaluated the prescribing and monitoring
of gentamicin for 14 months after the use of such a form was implemented. The
data collected included dosing, initial serum gentamicin concentrations, and
serum creatinine measurements. These data were compared with similar data
obtained during a period of 6 months before the order form was used. A total of
76 patient records were reviewed, 39 before the use of the order form and 47
after the order form was implemented. Gentamicin peak concentrations were
statistically higher in the group treated after the order form was implemented.
No differences were seen in gentamicin trough concentrations. The timely
measurement of serum gentamicin concentrations and serum creatinine levels was
improved in the group for whom the order form was used. The order form was
completed satisfactorily in 44 patients (94%). We conclude that implementing a
standardized order form improved the use of gentamicin.
PMID- 9655990
TI - Preventive health services and access to care for male veterans compared with
their spouses.
AB - The Veterans Health Administration is exploring ways to reform the current
Veterans Affairs (VA) system in accordance with the changing health care
environment of managed care. One proposal is for the VA to enlarge its patient
base by expanding eligibility to include spouses of veterans. To compare reported
preventive health care services received by male veterans and their spouses and
to measure whether spouses would choose to receive their medical care through a
VA medical center, we randomly selected 230 married male veterans and mailed self
administered questionnaires to be completed by them and their spouses; 170 (74%)
eligible subjects completed the questionnaire. The mean age of the veterans and
spouses was 73.6 and 67.4 years, respectively. Veterans reported significantly
higher rates of receipt of recommended preventive services than their spouses in
all 5 areas assessed, including blood pressure measurement; influenza,
pneumococcal, and tetanus vaccinations; and serum cholesterol measurement.
Veterans were significantly more satisfied than their spouses with their current
health care. Finally, 83% (95% confidence interval, 77% to 89%) of spouses
reported that they would choose to receive their medical care at the VA medical
center is allowed to do so. These findings suggest that spouses of male veterans
represent a sizable group that could be incorporated in the VA system, especially
given their strong desire to do so.
PMID- 9655991
TI - Quality of diabetes care for non-English-speaking patients. A comparative study.
AB - To determine the quality of care provided to non-English-speaking patients with
non-insulin-dependent (type 2) diabetes mellitus compared with English-speaking
patients, we did a retrospective cohort study of 622 patients with type 2
diabetes, of whom 93 were non-English-speaking and 529 were English-speaking.
They were patients at primary and specialty care clinics at a university and a
county hospital, and the study was based on clinical and administrative database
records with a 12-month follow-up. Professional interpreters were provided to all
non-English-speaking patients. Patients were identified using interpreter
services records, which reliably included all patients who did not speak English.
After adjusting for demographic differences, significantly more non-English
speaking patients received care that met the American Diabetes Association
guidelines of 2 or more glycohemoglobin tests per year (odds ratio, 1.9; 95%
confidence interval, 1.2-3.0) and 2 or more clinic visits per year (odds ratio,
2.6; 95% confidence interval, 1.2-5.4). More non-English-speaking patients had 1
or more dietary consultations (odds ratio, 2.8; 95% confidence interval, 1.3
6.1). No other significant differences were found in routine laboratory test use
or in the number of ophthalmologic examinations. Outcome variables also did not
differ, including standardized glycohemoglobin and other laboratory results,
complication rates, use of health services, and total charges. At these
institutions, the quality of diabetes care for non-English-speaking patients
appear to be as good as, if not better than, for English-speaking patients.
Physicians may be achieving these results through more frequent visits and
laboratory testing.
PMID- 9655992
TI - Feces, dead horses, and fleas. Evolution of the hostile use of biological agents.
AB - Selected events in the history of biological weapons are highlighted to increase
physicians' awareness of the threat of biological weapons. The hostile use of
biological substances originated in antiquity and pervades the history of human
conflict. Although difficult to verify at times, the use of such weaponry has not
been limited to national militaries. Disgruntled civilians and even physicians
have used biological weapons to promote their interests. Their potency, cost
effectiveness, and the ability to manufacture and deploy them with little
sophistication, or under the semblance of legitimate commercial endeavors, will
ensure that biological weapons remain a constant threat to public health.
PMID- 9655993
TI - Overview of anesthesia for primary care physicians.
AB - Primary care physicians are frequently asked to evaluate patients before elective
surgery. Familiarity with anesthetic technique and physiologic processes can help
primary care physicians identify risk factors for perioperative complications,
optimize patient care, and enhance communication with surgeons and
anesthesiologists. To this end, we review the physiologic processes accompanying
tracheal intubation and general and regional anesthesia. There is no convincing
evidence that regional anesthesia is safer than general anesthesia. In addition
to replacing fluid losses from the surgical field and insensible losses,
intraoperative fluid administration may attenuate the cardiovascular and renal
effects of anesthesia. Therefore, recommendations to limit fluids should be made
with caution and should be tempered with an understanding of intraoperative fluid
requirements. An understanding of the physiologic processes of anesthesia,
combined with preoperative risk stratification strategies, will enhance a primary
care physician's ability to provide meaningful preoperative evaluations.
PMID- 9655994
TI - Mild cobalamin deficiency.
PMID- 9655995
TI - Cardiac troponins in patients with chest pain.
PMID- 9655996
TI - Factors V Leiden and the prothrombin gene mutation: two common genetic defects
associated with thrombosis.
PMID- 9655997
TI - Prostate carcinoma: clarification through clinical insight and molecular
diagnostics.
PMID- 9655998
TI - Finding the iron in the melting pot--practical use of a new genetic assay for
hereditary hemochromatosis.
PMID- 9655999
TI - Homocysteine and vascular disease: emerging connections.
PMID- 9656000
TI - Follow-up testing after cancer treatment: is it indicated?
PMID- 9656001
TI - Noninvasive positive pressure mechanical ventilation.
PMID- 9656002
TI - Treatment of gastroesophageal reflux disease--1998.
PMID- 9656003
TI - Beta-adrenergic blockers in the management of heart failure.
PMID- 9656004
TI - Diabetes in older persons: special considerations.
PMID- 9656005
TI - Measles outbreak at a university without a two-dose immunization requirement.
PMID- 9656006
TI - 'Virtual' factitious disorders and Munchausen by proxy.
PMID- 9656007
TI - Medical marijuana.
AB - Although many clinical studies suggest the medical utility of marijuana for some
conditions, the scientific evidence is weak. Many patients in California are self
medicating with marijuana, and physicians need data to assess the risks and
benefits. The only reasonable solution to this problem is to encourage research
on the medical effects of marijuana. The current regulatory system should be
modified to remove barriers to clinical research with marijuana. The NIH panel
has identified several conditions for which there may be therapeutic benefit from
marijuana use and that merit further research. Marijuana should be held to the
same evaluation standards of safety and efficacy as other drugs (a major flaw in
Proposition 215) but should not have to be proved better than current medications
for its use to be adopted. The therapeutic window for marijuana and THC between
desired effect and unpleasant side effects is narrow and is a major reason for
discontinuing use. Although the inhaled route of administration has the benefit
of allowing patients to self-titrate the dose, the smoking of crude plant
material is problematic. The NIH panel recommended that a high priority be given
to the development of a controlled inhaled form of THC. The presence of a
naturally occurring cannabinoid-receptor system in the brain suggests that
research on selective analogues of THC may be useful to enhance its therapeutic
effects and minimize adverse effects.
PMID- 9656008
TI - Getting the work done.
PMID- 9656009
TI - Beware of what you say...
PMID- 9656010
TI - Prevalence and distribution of anorectal misdiagnoses.
PMID- 9656011
TI - Brucella abortus strain RB51 vaccine: its advantages and risks.
PMID- 9656012
TI - FSIS assessing risk of Salmonella enteritidis in eggs.
PMID- 9656013
TI - Beef quality assurance program may need further implementation.
PMID- 9656014
TI - Debate regarding homeopathic medicine continues.
PMID- 9656015
TI - Viewpoint on vaccination guidelines and alternative modalities.
PMID- 9656016
TI - Solution to pet overpopulation may involve change in perspective.
PMID- 9656017
TI - What is your diagnosis? Fracture of the caudal diaphysis of the left
ceratobranchial bone of the hyoid apparatus in a goose.
PMID- 9656018
TI - What is your neurologic diagnosis? Anomalous development of C3 and C4 resulting
in subluxation and spinal cord compression at C3-4.
PMID- 9656019
TI - Animal behavior case of the month. Stereotypical motor behavior that manifested
when the owner departed or was out of the dog's sight.
PMID- 9656020
TI - Municipal animal control ordinances--some legal issues.
PMID- 9656021
TI - Prevention of antibiotic residues in veal calves fed colostrum.
PMID- 9656022
TI - Adverse events associated with albendazole and other products used for treatment
of giardiasis in dogs.
PMID- 9656023
TI - Prevalence of fecal shedding of Salmonella organisms among captive green iguanas
and potential public health implications.
AB - OBJECTIVE: To determine prevalence of fecal shedding of Salmonella organisms
among captive green iguanas (Iguana iguana). DESIGN: Cohort study. ANIMALS: 12
captive green iguanas. PROCEDURE: Iguanas were isolated in an environmental
chamber, and fecal samples were collected weekly for 10 consecutive weeks.
Samples were incubated aerobically in tetrathionate broth for 18 to 24 hours.
Aliquots were then transferred to Hektoen and Salmonella-Shigella agar plates and
incubated for an additional 18 to 24 hours. Isolated colonies were subcultured on
nutrient agar slants, and Salmonella isolates were serogrouped and serotyped.
RESULTS: All 12 iguanas were found to be shedding Salmonella organisms at least
once during the study, and multiple serotypes were isolated from 7 of the 12.
Salmonella organisms were isolated from 88 of 106 (83%) fecal samples; 21 samples
contained multiple Salmonella serotypes. Overall, 11 Salmonella serotypes were
identified. In 74 of 100 instances, when a particular Salmonella serotype was
isolated from an individual iguana, the same serotype was also isolated from a
subsequent fecal sample from that iguana. CLINICAL IMPLICATIONS: Results
suggested that most iguanas have a stable mixture of Salmonella serotypes in
their intestinal tracts and intermittently or continuously shed Salmonella
organisms in their feces. Veterinarians should advise their clients on
precautions for reducing the risk of acquiring these organisms from their pets.
Public health officials trying to determine whether an iguana is the source of a
specific Salmonella serotype that caused infection in human patients should
submit at least 3 fecal samples collected from the iguana 1 week apart for
bacterial culture.
PMID- 9656024
TI - Association of Reptilian and Amphibian Veterinarians guidelines for reducing risk
of transmission of Salmonella spp from reptiles to humans.
PMID- 9656025
TI - Use of serologic testing to assess immune status of companion animals.
AB - At the November 1997 meeting of the AVMA Council on Biologic and Therapeutic
Agents, the Council recommended that the JAVMA publish an article on the current
status of the use of serologic testing in an effort to assist practitioners who
must make decisions regarding vaccination of companion animals (i.e., dogs, cats,
and horses). It is anticipated that the peer-reviewed article provided here will
be of benefit to veterinarians and will facilitate their attempts to maintain
animal health through the knowledgeable use of vaccines.
PMID- 9656026
TI - Occupational factors and reproductive outcomes among a cohort of female
veterinarians.
AB - OBJECTIVE: To estimate absolute and relative risks of preterm delivery (PTD) and
small-for-gestational-age (SGA) births among a cohort of female veterinarians in
relation to selected occupational factors, including clinical practice type
(CPT). DESIGN: Retrospective cohort survey. SAMPLE POPULATION: 2,997 female
graduates from US veterinary colleges between 1970 and 1980. PROCEDURE: Relevant
health and occupational data were collected through a self-administered mail
questionnaire with telephone follow-up of nonrespondents. Absolute and relative
risks of PTD and SGA births were estimated in relation to maternal CPT at the
time of conception and exposure to 13 occupational factors. Attempts were made to
control confounding by use of multiple logistic regression analyses. RESULTS:
Absolute and relative risks of PTD were highest for veterinarians employed in
exclusively equine clinical practice. Although several increased, none of the CPT
specific relative risk estimates were significantly different from the null value
of 1. Exposure-specific analyses indicated that occupational involvement with
solvents among exclusively small animal practitioners was associated with the
highest relative risk of PTD. A small number of SGA births limited information
that could be obtained from these analyses. Overall absolute risks of PTD and SGA
births among cohort members were much lower in comparison with the general female
population. CLINICAL IMPLICATIONS: Given the large number of women currently
practicing and entering the profession of veterinary medicine, clinical tasks
associated with potential reproductive hazards should be approached with
heightened awareness and increased caution, especially activities that may
involve exposure to solvents.
PMID- 9656027
TI - Serum distemper virus and parvovirus antibody titers among dogs brought to a
veterinary hospital for revaccination.
AB - OBJECTIVE: To determine serum canine distemper virus (CDV) and canine parvovirus
(CPV) antibody titers in healthy dogs brought to a veterinary hospital for
revaccination. DESIGN: Case series. ANIMALS: 122 dogs. PROCEDURE: Serum antibody
titers were measured by means of hemagglutination inhibition (CPV titers) or
serum neutralization (CDV titers) at the time dogs were brought to the hospital
for revaccination. All dogs had been vaccinated between 271 and 1,665 days
previously. Dogs were grouped by age, breed (purebred vs mixed breed), sex, and
weight to determine whether these factors were associated with antibody titers.
Serum CPV titers > or = 1:80 and serum CDV titers > or = 1:96 were considered
protective. RESULTS: Breed, sex, and weight were not significantly associated
with serum CPV and CDV titers. Age was significantly associated with CPV titer,
with younger dogs having higher titers, but was not associated with CDV titer.
Thirty-three of 122 (27%; 95% confidence interval, 19.0 to 34.9%) dogs had a less
than-protective CPV titer. Twenty-five of 117 (21%; 95% confidence interval, 13.6
to 28.4%) dogs had a less-than-protective CDV titer. CLINICAL IMPLICATIONS:
Results suggest that, on the basis of serum antibody titers, the current practice
of annual revaccination of dogs against CPV and CDV infection should be
maintained. Measurement of antibody titers to determine whether revaccination is
truly needed would seem justifiable in those dogs that have previously had an
adverse reaction to vaccination.
PMID- 9656028
TI - Use of infrared thermometry and effect of otitis externa on external ear canal
temperature in dogs.
AB - OBJECTIVE: To compare infrared thermometry with rectal thermometry as a method of
assessing core body temperature in dogs and to assess the effect of otitis
externa on external ear canal temperature (EECT). DESIGN: Prospective study.
ANIMALS: 650 dogs without history or clinical signs of otitis externa and 85 dogs
with recurrent or chronic otitis externa. PROCEDURE: Rectal temperature was
measured, using a mercury thermometer. External ear canal temperature was
measured, using an infrared tympanic thermometer. RESULTS: Measurements of body
temperature at the 2 sites did not agree. Sensitivity and specificity of infrared
thermometry in detecting fever, as determined by rectal thermometry, were 69.7
and 84.6%, respectively. Use of methods to predict rectal temperature from EECT
did not improve the accuracy of infrared thermometry. Otitis externa
significantly influenced EECT. CLINICAL IMPLICATIONS: Use of infrared thermometry
as a replacement for rectal thermometry in assessing core body temperature in
dogs was unsatisfactory. The 2 methods for measuring body temperature were not
interchangeable in dogs.
PMID- 9656029
TI - Preoperative variables affecting long-term outcome of triple pelvic osteotomy for
treatment of naturally developing hip dysplasia in dogs.
AB - OBJECTIVE: To determine whether preoperative radiographic evidence of
degenerative joint disease (DJD), hip joint laxity, or age at surgery is
associated with long-standing DJD or hip function in dogs with hip dysplasia (HD)
that had a triple pelvic osteotomy (TPO). DESIGN: Prospective study. ANIMALS: 34
dogs with HD. PROCEDURE: Dogs that had TPO performed during an 8-year period were
chosen for long-term follow-up evaluation that included physical examinations,
pelvic radiographs, and owner questionnaires. Data on radiographic evidence of
DJD, Norberg angle, and percentage of femoral head coverage were retrieved from
preoperative records and determined from follow-up radiographs. RESULTS:
Approximately 40% of dogs had progression of DJD. Eighty-seven percent of dogs
received excellent or good physical examination scores, and 76% received
excellent or good at-home activity scores. Preoperative and long-standing DJD
were not associated. The risk of DJD was increased with increased age at surgery,
narrower preoperative Norberg angle, and lower percentage of femoral head
coverage, but these variables were not associated with clinical hip function.
CLINICAL IMPLICATIONS: TPO for treatment of HD in dogs may slow, rather than
stop, radiographic progression of DJD; however, clinical outcome is acceptable
for most dogs. Preoperative evidence of DJD may not be a limiting criterion in
selecting dogs as suitable TPO candidates. Dogs with extensive hip joint laxity
before surgery may be predisposed to developing DJD; thus, the risk-to-benefit
ratio for TPO versus salvage procedures should be considered. Younger dogs may
develop less severe DJD after TPO; surgery should be considered at the first sign
of hip joint laxity and pain.
PMID- 9656030
TI - Response to long-term enzyme replacement treatment in dogs with exocrine
pancreatic insufficiency.
AB - OBJECTIVE: To study response to long-term enzyme replacement treatment in dogs
with exocrine pancreatic insufficiency (EPI). DESIGN: Cross-sectional study.
ANIMALS: 76 German Shepherd Dogs or rough-coated Collies with EPI and 145
clinically normal dogs of the same breeds. PROCEDURE: Questionnaires were sent to
owners of dogs with EPI and owners of clinically normal dogs. Dogs with EPI had
been given dietary enzyme supplements for at least 4 months. Relative frequency
distributions of gastrointestinal tract and dermatologic signs, prevalences of
typical signs of EPI (e.g., weight loss, ravenous appetite, yellow and pulpy
feces, high fecal volume), feeding regimens, and dietary intolerances were
compared between dogs with EPI and clinically normal dogs. RESULTS:
Gastrointestinal tract signs considered typical for dogs with EPI were almost
completely controlled with dietary enzyme supplements in half of the dogs with
EPI, and their general health was similar to that of clinically normal dogs. A
poor treatment response was found in a fifth of dogs with EPI that had several
signs that were typical of EPI. Signs most often persisting were high fecal
volume, yellow and pulpy feces, and flatulence. Dermatologic problems were
common, especially in German Shepherd Dogs with EPI. Treatment response was
irrespective of breed. Nonenteric-coated enzyme supplements, powdered enzyme, and
raw chopped pancreas were equally effective in controlling clinical signs.
Although dietary sensitivities were common, use of adjunctive dietary treatment
was minimal. Antibiotics were occasionally administered to half of the dogs with
EPI. CLINICAL IMPLICATIONS: Results of this study indicate that, with basically
similar treatment regimens, response to long-term enzyme treatment in dogs with
EPI varied considerably.
PMID- 9656031
TI - Pneumothorax secondary to Dirofilaria immitis infection in two cats.
AB - Dirofilariasis was diagnosed in 2 cats with spontaneous pneumothorax. One cat had
a 3-week history of a cough, and the other had an 11-month history of vomiting
and tachypnea. Pneumothorax was managed in cats by thoracocentesis and supportive
care. Diagnosis of dirofilariasis was made on the basis of heartworm antigen and
antibody test results and radiographic findings. Clinical signs of heartworm
infection improved after treatment with corticosteroids. Cats had good extended
outcomes. Heartworm disease should be one of the differential diagnoses
considered in cats with spontaneous pneumothorax.
PMID- 9656032
TI - Correlations between ultrasonographic findings and specific hepatic diseases in
cats: 72 cases (1985-1997).
AB - OBJECTIVE: To identify correlations between ultrasonographic findings and
specific hepatic diseases in cats. DESIGN: Retrospective study. SAMPLE
POPULATION: Medical records of 72 cats with a histopathologic diagnosis of
hepatic disease and diagnostic-quality abdominal ultrasonograms between 1985 and
1997. PROCEDURE: Abdominal ultrasonographic findings in 72 cats with
histologically confirmed hepatic disease (hepatic lipidosis excluded) were
reviewed. Rather than attempt to combine individual ultrasonographic findings
with specific hepatic diseases, 2 classification trees were created as models to
correlate certain groups of abnormalities with specific hepatic diseases or with
malignant and benign lesions of the liver. Sensitivity and specificity of
classification trees were calculated. RESULTS: Use of a classification tree
resulted in correct classification of malignant versus benign hepatic lesions in
88.9% of cats that had hepatic disease (sensitivity, 90.7%; specificity, 86.1%).
Use of a classification tree to distinguish individual types of hepatic diseases
resulted in mostly accurate classification of hepatic lymphosarcoma (sensitivity,
70.5%; specificity, 98.2%), cholangitis-cholangiohepatitis syndrome (sensitivity,
87%; specificity, 90%), and benign lesions of the liver (sensitivity, 84.6%;
specificity, 86.4%). Criteria that helped most in differentiating among various
hepatic diseases were abnormalities within other organs (spleen, lymph nodes) and
appearance of the hepatic portal system. A correlation was not found between
focal or multifocal appearance of hepatic lesions and specific hepatic diseases.
CLINICAL IMPLICATIONS: Use of classification trees to distinguish among specific
hepatic diseases or between malignant and benign hepatic lesions provides
potentially useful algorithms for ultrasonographic evaluation of cats with
hepatic disease.
PMID- 9656033
TI - Cycad palm toxicosis in dogs: 60 cases (1987-1997).
AB - OBJECTIVE: To report clinical and epidemiologic information, summarize
characteristic clinical signs and laboratory results, and describe the expected
course of cycad toxicosis in dogs. DESIGN: Retrospective study. ANIMALS: 60 dogs
with evidence of cycad ingestion. PROCEDURE: The National Animal Poison Control
Center's case record database was searched for records of dogs ingesting cycad
plants from January 1987 to November 1997. Data were retrieved on clinical signs,
laboratory test results, exposure history, and physical examination findings.
Cases were assessed as toxicosis, suspected toxicosis, or possible toxicosis.
RESULTS: Records from 60 dogs were retrieved; 89.7% of the dogs were from the
southern United States, 38.7% ingested seeds, 95% developed liver and
gastrointestinal tract problems, and 53.3% had abnormal neurologic signs. High
serum bilirubin concentration and alkaline phosphatase and alanine
aminotransferase activities were the most common serum biochemical abnormalities.
Although clinical signs were observed within 1 day, laboratory values did not
change for 24 to 48 hours after cycad ingestion. Mortality rate was reportedly
32.1%. CLINICAL IMPLICATIONS: 68% of dogs responded well to treatment and
supportive care. Dogs ingesting seeds are likely to develop more serious
problems. Clinical signs can develop within 1 to 3 days and can last for several
days. A tentative diagnosis should be made on the basis of history of ingestion,
clinical signs, and duration of signs. Because of the nature of these toxins,
cycad ingestion is serious and should be treated aggressively.
PMID- 9656034
TI - Paraneoplastic pruritus and alopecia in a horse with diffuse lymphoma.
AB - An 8-year-old castrated male Paint Horse was referred because of generalized
pruritus, alopecia, and intermittent fever. Results of gross evaluation of the
skin and microscopic evaluation of skin scrapings were inconclusive. Histologic
examination of skin biopsy specimens revealed vasculitis. The horse had
persistent hypercalcemia; therefore, lymphosarcoma was considered a possibility.
Ultrasonography revealed hypoechoic nodules within the parenchyma of the spleen
and liver. Results of microscopic evaluation of an aspirate from a splenic nodule
were suggestive of lymphosarcoma. The condition of the horse deteriorated, and it
was subsequently euthanatized. Postmortem examination revealed diffuse lymphoma.
In human beings, generalized pruritus may be an indication of serious internal
disease, including malignancy. Paraneoplastic pruritus is most common in patients
with Hodgkin's lymphoma but can also develop in patients with non-Hodgkin's
lymphoma, leukemia, or a solid neoplasm. Lymphoma should be considered in the
differential diagnoses when examining horses with generalized pruritus for which
another cause cannot be identified.
PMID- 9656035
TI - Clinical appearances, healing patterns, risk factors, and outcomes of horses with
fungal keratitis: 53 cases (1978-1996)
AB - OBJECTIVE: To compare initial clinical appearances, healing mechanisms, risk
factors, and outcomes of horses with fungal keratitis. DESIGN: Retrospective
analysis. ANIMALS: 52 horses (53 eyes) with fungal keratitis. PROCEDURE: Medical
records and clinical photographs of eyes were reviewed. Keratomycoses were
categorized on the basis of clinical appearance at initial examination and
pattern of healing. RESULTS: Five distinct forms of mycotic keratitis were
recognized. Of 53 affected eyes, 34 (64%) retained sight and had varying degrees
of corneal scarring after treatment, 6 (11%) had a cosmetic appearance but were
blind, and 13 (25%) were enucleated. Bacterial-like ulcers were the most frequent
type and the most difficult for predicting outcome. Eyes affected by superficial
fungal keratitis were likely to be chronically infected and to require
debridement and extended treatment but usually healed with minimal scarring.
Keratomycosis with a surrounding furrow resulted in a grave prognosis.
Aspergillus organisms were isolated from 9 of 10 such eyes. Cake-frosting
material was a positive prognostic sign. Fungal corneal stromal abscesses tended
to be caused by yeast. CLINICAL IMPLICATIONS: This information will aid
practitioners in recognizing various forms of fungal keratitis and guide them
when making therapeutic decisions and prognoses for affected horses.
PMID- 9656037
TI - The invisible profession.
PMID- 9656036
TI - Comparison of hypertonic saline-dextran solution and lactated Ringer's solution
for resuscitating severely dehydrated calves with diarrhea.
AB - OBJECTIVE: To determine effectiveness of rapid i.v. administration of hypertonic
saline-dextran (HSD) solution combined with oral administration of isotonic
electrolyte solution for resuscitating severely dehydrated calves and to compare
the resuscitative response with that of a conventional treatment of lactated
Ringer's solution (LRS) i.v. and orally administered isotonic electrolyte
solution. DESIGN: Prospective study. ANIMALS: 15 male dairy calves 3 to 10 days
old. PROCEDURE: Baseline data were obtained. Osmotic diarrhea and severe
dehydration were induced for 48 hours. Calves were then allocated to 3 treatment
groups. The control group (group C) did not receive fluids, a second group (group
H) received hypertonic saline (7.2% NaCl) solution with 6% dextran 70 and
isotonic electrolyte solution, and a third group (group L) received LRS and
isotonic electrolyte solution. Physical examinations were performed every 8
hours. RESULTS: Calves developed diarrhea, lethargy, severe dehydration (mean,
14% of body weight), azotemia, hyperkalemia, and mild acidemia. Group-C calves
remained lethargic and severely dehydrated during the 24-hour treatment phase.
Calves treated with HSD and LRS were effectively resuscitated; however, response
for most variables was more rapid and sustained for the HSD-treated group.
Cardiac output was greater in LRS- than HSD-treated calves 1, 2, and 8 hours
after initiation of treatment because of continued i.v. administration of fluids.
CLINICAL IMPLICATIONS: A combination of HSD and isotonic electrolyte solution was
a rapid and effective method for resuscitation of severely dehydrated calves. It
was similar in effectiveness to conventional treatment in which LRS and isotonic
electrolyte solution were used for resuscitating calves with severe dehydration.
PMID- 9656038
TI - Roles of acute care nurse practitioners, physician assistants, and resident
physicians in acute care settings.
PMID- 9656039
TI - A survey of endotracheal suctioning with instillation of normal saline.
AB - BACKGROUND: Instillation of normal saline before suctioning is a common nursing
intervention although little research supports the practice. OBJECTIVES: To
determine when and how often saline is used during suctioning and to assess the
knowledge of nurses and respiratory therapists of the advantages and dangers of
using saline during endotracheal suctioning. METHODS: A survey of nurses and
respiratory therapists working in adult ICUs was conducted in a large university
teaching hospital. RESULTS: Of the 187 respondents, 96 (51%) rarely instill
saline before suctioning, whereas 61 (33%) frequently use saline. Fifty-five
percent use saline to enhance retrieval of secretions, and 45% use it to
stimulate a cough. Nurses and respiratory therapists differ in their use and
understanding of saline instillation. Most nurses (64%) rarely use saline before
suctioning, whereas most respiratory therapists (71%) frequently use saline.
Respiratory therapists (57%) were more aware than were nurses (37%) of the
benefit of using normal saline to stimulate a cough. Nurses indicated more
adverse effects of instillation of normal saline, specifically oxygen
desaturation and increased risk of pulmonary infections, than did respiratory
therapists. CONCLUSION: The results of the survey helped determine target areas
for educational programs for nurses and respiratory therapists. A protocol is
being developed for use by all who do suctioning.
PMID- 9656040
TI - Instillation of normal saline before suctioning in patients with pulmonary
infections: a prospective randomized controlled trial.
AB - OBJECTIVE: To determine the effect of instillation of normal saline before
suctioning on oxygen saturation, heart rate, and blood pressure in patients with
pulmonary infections. METHODS: A prospective randomized controlled trial was
conducted in the surgical, medical, and burn/trauma ICUs of an academic medical
center. Eighteen men and 11 women (mean age = 60 years) receiving mechanical
ventilation who met the criteria for pulmonary infection were randomly assigned
to 2 groups. One group had instillation of a 5-mL bolus of normal saline before
suctioning; the other did not. Suctioning was done as needed during an 8-to 12
hour period. Oxygen saturation, heart rate, and blood pressure were measured
noninvasively immediately before and after suctioning, at 1-minute intervals for
5 minutes after suctioning, and at 10 minutes after suctioning. RESULTS:
Instillation of normal saline had an adverse effect on oxygen saturation, which
worsened over time. Differences in saturation between the 2 groups were
significant at 4, 5, and 10 minutes after suctioning. Differences in heart rate
and blood pressure were not significant. CONCLUSION: Instillation of normal
saline before suctioning has an adverse effect on oxygen saturation and should
not be used routinely in patients receiving mechanical ventilation who have
pulmonary infection.
PMID- 9656041
TI - Care activities and outcomes of patients cared for by acute care nurse
practitioners, physician assistants, and resident physicians: a comparison.
AB - BACKGROUND: Little information is available on the practice of acute care nurse
practitioners and physician assistants in acute care settings. OBJECTIVES: To
compare the care activities performed by acute care nurse practitioners and
physician assistants and the outcomes of their patients with the care activities
and patients' outcomes of resident physicians. METHODS: Sixteen acute care nurse
practitioners and physician assistants and a matched group of resident physicians
were studied during a 14-month period. Data on the subjects' daily activities and
on patients' outcomes were collected 4 times. RESULTS: Compared with the acute
care nurse practitioners and physician assistants, residents cared for patients
who were older and sicker, cared for more patients, worked more hours, took a
more active role in patient rounds, and spent more time in lectures and
conferences. The nurse practitioners and physician assistants were more likely
than the residents to discuss patients with bedside nurses and to interact with
patients' families. They also spent more time in research and administrative
activities. Few of the acute care nurse practitioners and physician assistants
performed invasive procedures on a regular basis. Outcomes were assessed for 187
patients treated by the acute care nurse practitioners and physician assistants
and for 202 patients treated by the resident physicians. Outcomes did not differ
markedly for patients treated by either group. The acute care nurse practitioners
and physician assistants were more likely than the residents to include patients'
social history in the admission notes. CONCLUSIONS: The tasks and activities
performed by acute care nurse practitioners and physician assistants are similar
to those performed by resident physicians. However, residents treat patients who
are sicker and older than those treated by acute care nurse practitioners and
physician assistants. Patients' outcomes are similar for both groups of subjects.
PMID- 9656042
TI - Patients' outcomes: intrahospital transportation and monitoring of critically ill
patients by a specially trained ICU nursing staff.
AB - BACKGROUND: Intrahospital transportation of critically ill patients can
contribute to patients' morbidity and mortality. OBJECTIVE: To determine adverse
outcomes associated with intrahospital transportation of critically ill patients
by a specially trained nursing transport team. METHODS: Monitoring and
intervention data were collected for 237 instances of transportation of patients
between a hospital's ICUs and radiology suites. These results were compared with
the results of national studies on complication rates associated with
intrahospital transportation of patients. RESULTS: The patients moved by the
specially trained transport team has a 15.5% overall complication rate, with
10.2% minor, 2.5% moderate (compensated for with medications), and 2.8% severe
complications that did not respond to intervention. No medications of therapies
were delayed, and only 2 patients (0.8%) had decompensation that required the
examinations to be aborted. Reported national complication rates for
intrahospital transportation of patients are as high as 75%; the complications
include adverse events such as delayed administration of medications, significant
changes in vital signs, dislodgment of artificial airways and i.v. catheters, and
cardiopulmonary arrest. CONCLUSION: Use of a specially trained ICU transport team
can substantially reduce the rate of adverse outcomes generated by the
transportation of critically ill patients for specialized radiological
procedures.
PMID- 9656043
TI - Effect of a back massage and relaxation intervention on sleep in critically ill
patients.
AB - BACKGROUND: Critically ill patients are deprived of sleep and its potential
healing qualities, although many receive medications to promote sleep. No one has
adequately evaluated holistic nonpharmacological techniques designed to promote
sleep in critical care practice. OBJECTIVES: To determine the effects of (1) a
back massage and (2) combined muscle relaxation, mental imagery, and a music
audiotape on the sleep of older men with a cardiovascular illness who were
hospitalized in a critical care unit. METHODS: Sixty-nine subjects were randomly
assigned to a 6-minute back massage (n=24); a teaching session on relaxation and
a 7.5-minute audiotape at bedtime consisting of muscle relaxation, mental
imagery, and relaxing background music (n=28); or the usual nursing care
(controls, n=17). Polysomnography was used to measure 1 night of sleep for each
patients. Sleep efficiency index was the primary variable of interest. One-way
analysis of variance was used to test for difference in the index among the 3
groups. RESULTS: Descriptive statistics showed improved quality of sleep among
the back-massage group. Initial analysis showed a significant difference among
the 3 groups in sleep efficiency index. Post hoc testing with the Duncan
procedure indicated a significant difference between the back-massage group and
the control group; patients in the back-massage group slept more than 1 hour long
than patients in the control group. However, the variance was significantly
different among the 3 groups, and reanalysis of data with only 17 subjects in
each group revealed no difference among groups (P=.06). CONCLUSIONS: Back massage
is useful for promoting sleep in critically ill older men.
PMID- 9656044
TI - Intra-aortic balloon pump: nursing implications for patients with an iliac artery
approach.
AB - Long-term use of an intra-aortic balloon pump is often necessary for patients
with severe left ventricular dysfunction who are awaiting cardiac
transplantation. Complications caused by prolonged bed rest and immobility can
occur when the traditional femoral approach is used for insertion of the balloon
catheter. Insertion of the intra-aortic balloon catheter through the iliac artery
is an alternative technique that allows patients to sit, stand, and walk while
receiving counterpulsation. This approach is now being used to prevent the
complications of immobility in patients awaiting cardiac transplantation. In this
article, the special considerations, potential complications, and nursing
interventions unique to the iliac artery approach are delineated.
PMID- 9656045
TI - Manual versus mechanical compression for femoral artery hemostasis after cardiac
catheterization.
AB - BACKGROUND: Most cardiac catheterizations are performed via femoral artery
access. Reported rates of both peripheral vascular complications and success
rates for the use of manual and mechanical compression techniques to achieve
femoral artery hemostasis after cardiac catheterization vary. OBJECTIVE: To
determine is use of a mechanical clamp is as effective as standard manual
pressure for femoral artery hemostasis after cardiac catheterization. METHODS:
Subjects consisted of 720 patients from 2 community hospitals who had elective
diagnostic cardiac catheterization via the femoral artery. The control group
(n=343) received manual compression for hemostasis; the study group (n=377)
received mechanical compression. Standard protocols were used for the 2
compression techniques. Pressure was applied for a minimum of 10 minutes for 5F
and 6F sheaths and catheters and for a minimum of 15 minutes for 7F and 8F
sheaths and catheters. Prospective data were collected and analyzed for each
patients, including sheath or catheter size, blood pressure, height, weight, age,
time from administration of local anesthetic to successful cannulation of the
femoral artery, anticoagulation status, total compression time, physician
performing the catheterization procedure, nurse or technician who obtained
hemostasis, and complications. In follow-up, patients were asked site-specific
and functional status questions 1 to 2 days after the catheterization procedure
and again 3 days after the catheterization procedure. RESULTS: Data were analyzed
by using frequency distributions, measures of central tendency, and measures of
variability. Only 1 difference between the 2 groups was significant: manual
compression time was 14.93 +/- minutes, whereas mechanical compression time was
17.13 +/- minutes. CONCLUSION: Mechanical compression is as effective as manual
compression for femoral artery hemostasis after cardiac catheterization.
PMID- 9656046
TI - In-hospital first-responder automated external defibrillation: what critical care
practitioners need to know.
AB - Despite the development and widespread implementation of Basic Life Support and
Advanced Cardiac Life Support, the percentage of patients who survive in-hospital
cardiac arrest has remained stable at approximately 15%. Although survival rates
may approach 90% in coronary care units, survival rates plummet outside of these
units. The lower survival rates for cardiac arrest that occur outside of the
coronary care unit may relate to the time elapsed between the onset of
ventricular fibrillation and first defibrillation. The advent of automated
external defibrillators has made it possible to decrease the time elapsed before
first defibrillation in non-critical care areas of the hospital. First responders
need only recognize that the patient is unresponsive, apneic, and pulseless
before attaching and activating the automated external defibrillator. Our
research shows that, as part of Basic Life Support training, non-critical care
nurses can learn to use the device and can retain the knowledge and skill over
time. Establishing an in-hospital automated external defibrillator program
requires commitment from administration, physicians, and nursing personnel.
Critical care practitioners should be aware of this technology and the literature
that supports its safety and effectiveness when used by non-critical care first
responders. Critical care nurses are in a unique position to effect changes that
will decrease the time between the onset of cardiac arrest and first
defibrillation.
PMID- 9656047
TI - The ECG in cardiac stress testing: a valuable, but unappreciated source of clues.
AB - The ECG exercise stress test is a very potent aid to the clinical diagnosis of
CAD. Thorough knowledge of the ECG abnormalities and clinical features related to
the stress test are required for an accurate diagnosis. The ECG exercise stress
test is not a substitute for clinical acumen. Proper evaluation of the stress
test is a clinical art of the skilled clinician. ECG exercise stress testing can
be done efficiently and effectively by trained emergency department physicians.
As a result, the diagnosis of CAD can be greatly accelerated.
PMID- 9656048
TI - Results of cardiac troponin I.
PMID- 9656049
TI - Integrating technology with compassionate care: withdrawal of ventilation in a
conscious patient with apnea.
PMID- 9656050
TI - Malignant hyperthermia.
PMID- 9656051
TI - All the king's horses and all the king's men. Three forms of curative audience in
the recovery from psychosis.
AB - This essay discusses an overlooked ingredient in the psychotherapy of psychosis
which is termed the "curative audience." Central to the equation of psychological
selfhood is the evocation of a sense of self by experiences that the patient has
with objects in the environment. This essay calls attention to an essential
function of this environment, namely, that it provides an audience that makes it
possible for these "selfobject" transferences, transference interpretations or
new, helpful relational experiences to become significant. In essence, it is
argued that a "private experience" without an internal or external audience is
not therapeutic in the reassembly of self, especially when the power and
intensity to overcome psychotic disintegration is required. The idea that the
psychotic patient recompensates not only with the help of a therapist but under
the auspices of a third entity, has not been previously discussed. Interestingly,
all the schools of psychoanalysis have touched on the role of audience in the
healing of patients with both neurosis and psychosis, yet this thread has not
been followed into its binding together of subjectivity. Three forms of curative
audience can be identified corresponding to the beginning, middle, and end phases
of treatment. The role of audience in the reassembly of the self is taking its
first form in the initial contact or initial relationship with the other and over
time develops into the second form, the therapeutic alliance. In the third form
of the curative audience, the establishment of an external selfobject milieu that
performs the functions of the curative audience is seen as essential to continued
cohesion in the recovery from psychosis. Performative statements exert self
cohering effects and can be seen to have their source in the curative audience.
Two clinical vignettes were presented to illustrate these ideas.
PMID- 9656052
TI - The contributions of self psychology to the treatment of anorexia and bulimia.
AB - This article reviews the contribution of self psychology to the treatment and
understanding of anorexia and bulimia. It tries to show that the unique
conceptualization of self, selfobject relations, and this theory's
conceptualization of resistance and defenses constitutes a therapeutic stance
which especially fits the therapeutic needs of eating-disordered patients.
Clinical vignettes illuminate three main issues exemplifying the opportunities
and dilemmas that this new development in psychoanalytic theory brings to the
fore in the treatment of eating disorders: (1) empathy with deeds and attitudes
of the patient that the therapist finds difficult to empathize with; (2) empathic
understanding "from within" from an experience-near stance vs. experience-distant
interpretation "from without"; (3) self, selfobject relations with food and as a
result of progress in therapy, with human beings.
PMID- 9656053
TI - Responsibilities of the psychotherapy supervisor.
AB - The art and skill of psychotherapy supervision and its teaching have received
relatively little attention compared to their importance in psychiatric
education. Supervision is a complex task, requiring teaching and clinical skills,
as well as an awareness of the numerous responsibilities of the position. We
describe the responsibilities of the supervisor and group them to include those
to the supervise, to the patient, to the training program and profession, and to
the supervisor himself or herself. The core responsibility to supervise is
teaching them how to be psychiatrists, which for supervisors requires a balance
between a hierarchical and collaborative approach. The primary responsibility to
patients is that of assuring satisfactory treatment. Evaluating supervise within
an educational framework is the primary responsibility to the training program
and profession. Finally, the responsibilities to the supervisors themselves
include self-examination during the supervision process and general ongoing
education. Several themes are highlighted. One theme, which is a central
development in the understanding of supervision, is seeing the supervisor as a
participant in the supervisory process, rather than an outside observer of the
therapy process. Another theme is that these responsibilities are at times
competing, requiring the supervisor to establish priorities. Vignettes are used
throughout to illustrate the problems and subtleties of supervision.
PMID- 9656054
TI - Cultural intersections in the psychotherapy of borderline personality disorder.
AB - Psychotherapy can be essentially considered a journey in which two individuals
embark, each carrying a formidable cultural legacy. The psychotherapeutic
enterprise then becomes a succession of stops and intersections as the two
protagonists struggle to identify their culturally determined behaviors, using
culturally determined procedures to take care of them. In this sense, cultural
procedures are not a technical term but the appropriate combination of learned
concepts, experiential modifiers, and common sense indicators of contemporary
realities both at the individual and collective levels. The fascinating and
challenging nature of BPD does have a significant cultural component encompassing
explanatory, interpretive, pathogenic, pathoplastic, diagnostic/nosological, and
service management aspects. It is in the psychotherapeutic arena, however, where
both patient and therapist must face a multitude of culturally determined
situations that may have a significant impact on the outcome of treatment.
Culture can help the therapist to dispose of misleading clinical labels, with
obvious advantages for the patient's well-being. Psychotherapy can correct the
pathogenic elements of the patient's culture, recognize the pathoplastic clothing
of the patient's symptoms, and provide culturally sanctioned and valued success
experiences that may increase self-esteem, strengthen stability and,
particularly, contribute to the patient's achievement of an identity with which
he or she can feel comfortable. Finally, it must be remembered that it is not up
to the therapist to offer infallible explanatory models of the patient's plight,
but only culturally acceptable premises on which to build such explanations. On
the other hand, it is up to the therapist to recognize the "idioms of distress,"
both physical and psychological, that the patient conveys in the
psychotherapeutic context which is, as had been said many times here, totally
immersed in the environment of culture. Two vignettes illustrate several of the
issues under discussion.
PMID- 9656055
TI - Otto F. Kernberg, M.D., F.A.P.A., developer of object relations psychoanalytic
therapy for borderline personality disorder. Interview by Lata K. McGinn.
PMID- 9656056
TI - Treatment of homophobia in a gay male adolescent.
AB - Gay teenagers experience normal adolescent developmental processes, but need
assistance negotiating the effect of homophobia on their development. Homophobia
in the early phase may increase reliance upon the family. This can make it
difficult to extricate oneself from family sufficiently to develop peer
relationships. Supportive individual and interpretative family work can help
modify these problems. Problems in the middle phase are associated with societal
homophobia in the institutions where adolescents develop. High school social
dynamics support homophobia and make opportunities to develop a peer network
difficult. Therapeutic interventions that support a gay teen's efforts through
fantasy and symbolic action are key to success in to this period. Referral to gay
teen support groups are more likely to be successful during this phase. During
the late phase of adolescence, homophobia complicates the quest for an acceptable
social role and the need for more intimate relationships as plans for work and
pairing become the focus. The therapist helps the gay teen overcome stereotypes
and see themselves as individuals and as a members of a group called "gay." This
makes it possible to integrate personal aspects of the self with gay-group
identity.
PMID- 9656057
TI - Reconsidering the transference paradigm in treatment with the bereaved.
AB - What is to be expected of bereaved people years after a loss? How will life be
lived following the conclusion of the mourning process? Answers to questions such
as these are inherent in the use of terms such as recovery following loss or the
resolution of bereavement. From the perspective of the Two-track Model of
Bereavement, it should be clear that the outcome of loss needs to be examined
along the dimension of functioning, where the term recovery might well be
adequate, and along the dimension of the continuing relationship to the deceased,
where resolution would be the more precise term. When one considers the impact of
bereavement upon the individual years following the loss, it is well to keep in
mind that both recovery and resolution range across the continuum, with varying
degrees of adjustment, coping, and continued relationship to the representations
of the deceased neither fixed nor static. In many ways, the continuing
relationship to the deceased is similar to the relationships we have with living
individuals. The more comfort and openness characterize the connection to
memories and thoughts of a particular relationship, the greater the likelihood
that the relationship is not a focus of conflict or difficulty requiring
intervention. Changes in the relationship to the deceased will continue across
the life-cycle. The presence of flexibility and resilience in the internal object
world are important features of the individual's ability to deal with the ebb and
flow of a life course.
PMID- 9656058
TI - An effective analytical psychotherapy in crosscultural context. An East Asian
student in the United States.
AB - An effective analytical psychotherapy of a severe anxiety disorder with panic, in
a crosscultural context of East Asia and the United States, specifically a
Japanese student studying English, is presented. What was crucial in facilitating
the therapeutic process was an introduction of analytical way of looking at life
born of Western culture into an integrative orientation of Asian culture and
mentality.
PMID- 9656059
TI - Time-limited group treatment of children.
PMID- 9656060
TI - [Multiresistant tuberculosis in Spain: threat or fact?].
PMID- 9656061
TI - [Cough variant asthma. Clinical and functional characteristics. Report of 63
cases].
AB - To study the characteristics of our outpatient clinic patients presenting with
chronic cough as the sole symptom of bronchial asthma, and to evaluate the
bronchial hyperreactivity of such patients in comparison with that of classic
asthmatic patients with normal spirometry. For 3 years we studied 193 consecutive
patients with chronic cough as the sole symptom, using the study protocol
specified in the section on patients and methods. Sixty-three patients were
diagnosed of bronchial asthma. Bronchial hyperreactivity was considered to be the
cause of coughing based on reversibility testing or a positive methacholine test,
along with response to specific antiasthmatic therapy. Forty-six (73%) of the 63
patients had unproductive cough and 28 (44%) coughed mainly at night. In 14 (22%)
symptoms began with an upper respiratory tract infection. Wheezing could be heard
in only 4 (6%). Diagnosis was based on reversibility in 11 (17%) and methacholine
testing in 52 (83%). Mean PC20 was higher in patients diagnosed of variant cough.
Unlike classic asthma, persistent and usually unproductive cough caused by asthma
has few or no accompanying symptoms. The diagnostic yield of methacholine testing
is high in such patients.
PMID- 9656062
TI - [Usefulness of transbronchial punction and mediastinoscopy in mediastinal nodal
staging of non-microcytic bronchogenic carcinoma. Preliminary study].
AB - Preliminary study to compare the sensitivity and specificity of transbronchial
needle aspiration (TBNA) and mediastinoscopy/anterior mediastinotomy (MED/AMED)
and/or thoracotomy for staging of mediastinal nodes in non-small cell carcinoma.
To determine the sensitivity and specificity of computerized tomography (CT) as a
screening technique. Thirty-three patients with non-small cell carcinoma but no
remote metastasis and good lung function were evaluated. A chest CT scan was
performed before bronchoscopy in 27 patients and before surgery in the others.
Nodular areas considered diseased based on CT images were staged by TBNA. When CT
images were not available before bronchoscopy. TBNA for staging was performed in
the subcarinal region. Results by TBNA were compared with those obtained by
MED/AMED and/or thoracotomy. The prevalence of metastatic nodular disease was
47%. CT detected enlarged mediastinal nodes in 24 patients; the images were
considered normal in 9 patients. Sensitivity and specificity of CT was 93% and
54%, respectively, with a positive predictive value (PPV) of 68% and negative
predictive value (NPV) of 87.5%. The sensitivity and specificity of MED/AMED were
73% and 100%, respectively; PPV was 100% and NPV was 75%. The sensitivity and
specificity of TBNA were 36% and 92%, respectively; PPV was 83% and NPV was 57%.
The pneumothorax with pleural empyema suffered by one patient after MED could
have been avoided, given that the earlier TBNA was positive. TBNA is a safe,
useful technique for staging nodes in non-small cell carcinoma. Although the
sensitivity of TBNA is lower than that of MED, regions that are difficult to
reach with the latter technique can be sampled by TBNA. Furthermore, MED can be
rendered unnecessary by positive TBNA results. CT imaging of the chest is
sensitive but its specificity is low for detecting ganglial metastasis.
PMID- 9656063
TI - [Symptoms of sleep apnea syndrome in the general population].
AB - The aim of this study was to determine the clinical features of patients with
sleep apnea syndrome (SAS) in the general population. One hundred ten individuals
were selected randomly from the census and given hospital appointments. Case
histories were taken and complete physical examinations were made. Nighttime
respiratory polysomnograms were performed. Twenty-two (20%) of the 110 subjects
presented SAS. In the SAS group, 59.1% were habitual snorers and 22.7% reported
daytime hypersomnolence. The SAS patients has a mean age of 59.6 +/- 8.8 years
and 45.4% showed alterations of the pharynx. No differences in spirometric
variables were observed. Only age and daytime hypersomnolence predicted SAS in
the multivariate analysis. We conclude that the prevalence of snoring, daytime
hypersomnolence, pharyngeal alterations are higher in patients with SAS. The
patients are also older. Only age and daytime hypersomnolence predicted of SAS.
PMID- 9656065
TI - [Molecular biology in the diagnosis and treatment of respiratory diseases].
PMID- 9656064
TI - [Results of surgical treatment of non-microcytic bronchopulmonary carcinoma in
III-A stage].
AB - To analyze results and survival after surgical treatment of various stage III-a
subgroups. We reviewed 748 case histories of patients with non-small cell
bronchopulmonary carcinoma between January 1970 and December 1991, selecting 121
patients who underwent resection of stage III-a tumors, according to the
pathologist's report. Overall survival at 3, 5 and 10 years was 26, 16 and 12%,
respectively. The subgroup with better response to treatment was that of patients
with T-3 tumors (peripheral), N-0, with survival of 21% at five years. If
peribronchial and/or hilar (N-1) nodes were affected, survival was slightly less
(16%). If mediastinal adenopathy (N-2) was present, there were no survivors after
3 years. In this same T-3 group, but with neoplastic invasion of the pericardium,
mediastinal pleura or principal bronchi, survival after 3 years was nil. The
survival rates of peripheral T-3 patients undergoing block resections were 27, 20
and 17% at 3, 5 and 10 years, respectively, 16% at 2 years and 0% at 5, for those
with extrapleural resection. Patients with the poorest response to treatment were
those with mediastinal nodes (N-2), in whom survival was 17, 12 and 8% at 3, 5
and 10 years, respectively. In the 34 patients received postoperative irradiation
of the mediastinum, survival was 16% higher. The survival rates after 5 years
were similar for epidermoid carcinoma (18%) and adenocarcinoma (14%). The results
of surgical treatment are variable and depend on several factors: extension and
extrapulmonary location of lesions, surgical technique used for T-3 tumors and
histological type.
PMID- 9656066
TI - [Pancoast syndrome caused by lung tuberculosis].
AB - Pancoast's syndrome arises from neoplasms in 95% of cases but infection is a rare
cause. We describe a patient with Pancoast's tumor secondary to tuberculosis.
Pain caused by plexopathy and lack of diagnosis by noninvasive means led to the
need for open biopsy.
PMID- 9656067
TI - [Agenesis of the left pulmonary artery in an asymptomatic young woman].
PMID- 9656068
TI - [Askin's+ tumor in childhood. Considerations after a 2-year follow-up].
PMID- 9656069
TI - [Bronchial carcinoid: unusual recurrence as probable endobronchial metastasis].
PMID- 9656070
TI - [Mediastinitis and pleural effusion secondary to parenteral nutrition solution
extravasation].
PMID- 9656071
TI - [Malignant pheochromocytoma: one of the causes of lung metastasis with prolonged
survival].
PMID- 9656072
TI - [Recurrent mediastinal liposarcoma].
PMID- 9656073
TI - [Varices of pulmonary veins: infrequent cause of lung nodules].
PMID- 9656074
TI - [Exacerbation of COPD by Escherichia coli. Antibiotic treatment in exacerbations.
Should we extend the standard?].
PMID- 9656075
TI - [Infection of the low airways caused by Neisseria meningitidis and Streptococcus
pneumoniae in a patient with AIDS].
PMID- 9656076
TI - [Lung sclerosing hemangioma: cytohistologic inconsistency and clinical
implications].
PMID- 9656077
TI - [What is heart failure?].
PMID- 9656078
TI - [Phenotype and reactivity of T-lymphocytes isolated from atheromatous plaque.
Knowledge obtained from a transplant case].
AB - The primary immunologic hypothesis assumes that the initial damage in
atherosclerotic lesions is mediated by T lymphocytes reactive to heat shock
proteins, lipoproteins, bacteria, virus or even donor MHC antigens. A frequent
cause of heart transplant failure is the de novo formation of atheromatous
lesions in the vessels of the transplanted organ despite their absence in the
donor, thus suggesting that new lesions are secondary to a cellular immune
response by the receptor. In this study we determined the phenotype and the
reactivity of T cells from peripheral blood and from endomyocardial and
atherectomy biopsies obtained from the same immunosuppressed patient who
underwent a heart transplant in 1989. A panel of homozygous HLA-typed, Epstein
Barr virus transformed B lymphocytes were used as stimulators in functional
assays. Our results showed an important increase in the percentage of CD4+ cells
in the atheromatous plaque as well as in the endomyocardium, and a considerable
amount of TCR sigma+ lymphocytes in the atheromatous plaque. A considerable loss
of alloreactivity to HLA antigens was also observed. These results suggest that
although there are adequate conditions to mount a cellular immune response a
state of cellular anergy exists towards HLA antigens probably as result of
prolonged immunosuppressive therapy. The presence of obstructive lesions in this
particular patient don't seem to be secondary to HLA alloreactivity but could be
secondary to a switch in the cellular immune response as a consequence of chronic
exposure to some donor antigen, thus explaining the increased proportion of TCR
sigma+T lymphocytes.
PMID- 9656079
TI - [Coronary stent in acute myocardial infarction].
AB - From December 1995 to March 1997 fifty patients with acute myocardial infarction,
had 57 stents implanted. Mean time since the beginning of symptoms to the
procedure was 3.7 +/- 2.9 hours. Twenty-four stents were implanted "de novo", 17
for "sub-optimal" results, 5 for threatened closure and eleven for complex
dissection. The arteries treated with stent were left anterior descending in 42%,
right coronary in 42%, circumflex in 10%, vein grafts in 4%, intermedial branch
in 1% and marginal obtuse branch in 1%. Stent used in most of the cases was AVE
in 67% followed by Palmaz-Schatz, Wiktor, Crown, Gianturco-Roubin and Wallstent.
Before procedure, coronary flow was TIMI 0 in 66% TIMI 1 in 10% and TIMI 2 in
24%. After procedure, TIMI 3 coronary flow was achieved in 92% of the arteries
and other four had "no-reflow" phenomenon. Mean stenosis before procedure was 96%
+/- 3.1 and after stenting was 1.76% +/- 2.6 with a stent/artery diameter rate of
1.01. Technical success was 100% and clinical success was achieved in 96% of the
cases. Two cases were not successfully due to acute thrombotic closure in one
patient and in another one because of cardiogenic shock after two days of a
technical successful implantation of stent in LAD artery. There were not
recurrent ischemic events (CABG, re-infarction or new coronary angioplasty
procedure). Other two patients died for non-cardiac events (acute pancreatitis in
one and by septic shock in other). At the time of discharge 96% of patients were
treated with aspirin and ticlopidine. Major hematoma was evident in only one
case. At a mean follow-up time of 5.6 months +/- 4.2 in 45 patients showed that
73% were in functional class I and none of them had re-infarction, death or
needed a new revascularization. CONCLUSION: Stent implantation in acute
myocardial infarction is feasible and safe procedure with a low rate of ischemic
recurrent events.
PMID- 9656080
TI - [Radiofrequency ablation in the treatment of supraventricular arrhythmias in
pediatrics. Experience with 203 consecutive patients].
AB - We report the results of radiofrequency catheter ablation in 203 patients under
18 years of age with supraventricular tachyarrhythmias between April 1992 and
June 1997. The presence of an accessory pathway caused the tachyarrhythmia in 181
patients (89.1%) with a total of 187 accessory pathways; atrioventricular nodal
reentry caused the arrhythmia in 18 patients (8.8%) and atrial flutter in only 4
patients (1.9%). We eliminated the accessory pathway in 171 patients (91.4%), 23
patients showed recurrence of the tachycardia and we had complications in 4
patients (2.1%). The procedure was successful in the treatment of the
atrioventricular nodal reentry in the 18 cases, with ablation of the slow pathway
in 17 cases and in only one patient of the fast pathway, one patient showed total
A-V block, and recurrence of the arrhythmia in 3 cases (16.6%). Finally the
procedure was successful in the 4 cases of atrial flutter with one recurrence
(25%). In the total of the series, the radiofrequency catheter ablation was
successful in 193 patients (95%), with recurrence of the arrhythmia in 27 cases
(13.3%) and with complications in only 5 patients (2.6%). Radiofrequency catheter
ablation is a safe and effective procedure for the definitive treatment of
supraventricular tachyarrhythmias in children.
PMID- 9656081
TI - [Estimation of cardiac vagal reserve by dynamic exercise in patients with recent
myocardial infarction].
AB - In patients with coronary artery disease, the risk of sudden death is related to
the degree of left ventricular dysfunction and to cardiac parasympathetic
activity. The relation between these two consequences of myocardial infarction is
still the matter of intense controversy. In this investigation, we have estimated
the resting cardiac parasympathetic tone and assessed the left ventricular
systolic function of 25 patients who had suffered an acute myocardial infarction.
The absolute increase in heart rate recorded in the first 10 seconds of a
programmed dynamic exercise, was considered as the resting cardiac
parasympathetic tone or cardiac parasympathetic reserve. Twenty five age and sex
matched normal sedentary subjects were used as controls. Patients showed a
significantly smaller increase in their heart rate (16 +/- 4 lats/min, M +/- DS)
than the controls 32 +/- 5 P < 0.0001), during the first 10 seconds of exercise.
Moreover, the absolute increase in heart rate was inversely related to the degree
of left ventricular dilatation ( r = - 0.71, P < 0.0001) and directly related to
the left ventricular ejection fraction (r = 0.84, P < 0.0001). In other words,
those patients with larger left ventricles and depressed ventricular function had
a more prominent reduction of their resting cardiac parasympathetic tone. These
results indirectly suggest that, left ventricular size and function are indeed
related to cardiac parasympathetic activity.
PMID- 9656082
TI - [Prevalence of carotid atherosclerosis in a cohort of Mexico City].
AB - In order to investigate the prevalence of atherosclerosis in Mexico, high
resolution ultrasound and color Doppler flow imaging of carotid arteries were
carried out in a group of participants in CUPA project, a cohort study started in
1989 among persons 60 years and older living permanently in a high rise in Mexico
City. Imaging studies included identification of 4 atherosclerosis related
abnormalities: 1) intima media thickness; 2) kinkings and tortuousness; 3) non
stenosing plaques; and 4) significant carotid stenosis (> 50%). Analysis of 198
Doppler ultrasonographic studies in 56 males and 142 females showed an overall
prevalence of atherosclerosis related lesions of 65.6%, with increasing frequency
by age groups: 33% in younger than 65 year-old, 71% in 65-74 years, and up to 88%
in the 75 years and older group. The prevalence of high grade stenosis was low
(6%) whereas the overall frequency of non-stenosing plaques and intima-media
thickness was higher than 60%. Intima-media thickness was more common in males
while non-stenosing plaques and high grade stenosis were more frequent in
females. However, there were not significant differences among women and men when
atherosclerotic lesions were analyzed by age groups. This is the first report on
the prevalence of atherosclerosis in a Mexican population using ultrasonography.
Findings of the investigation document the high prevalence of atherosclerosis
among elderly resident in Mexico City.
PMID- 9656083
TI - [Vector electrocardiographic findings in chronic Chagas cardiomyopathy].
AB - Dilated Cardiomyopathy (DCM) is associated with many diseases. By means of
epidemiologic, clinical and invasive diagnostic techniques, the etiology of DCM
is identified almost in 50% of the cases. Chronic infection with Trypanosoma
cruzi is recognized as a cause of DCM in Latin America. A blind study of 40 cases
of DCM explores the electrovectorcardiographic data obtained in chronic chagasic
cardiomyopathy (CCC). Twenty one of 40 patients fulfilled epidemiologic and
seroimmunologic criteria for CCC, 19 had DCM. There were not differences between
these groups in regard to sex or age. Patients suffering DCM had in addition
diabetes mellitus, systemic hypertension or ischemic heart disease. Those with
CCC had not comorbid diseases in 50% of the cases. Arrhythmias and conduction
blocks were equally recognized in both groups, as well as ECG evidence of injury
or necrosis (p > 0.05). However, ECG signs of subepicardial ischemia were a
dominant feature in patients with CCC and normal epicardial coronary arteries (p
< 0.05). Probably this finding is due to a small vessels damage, a pathogenic
mechanism proposed in CCC.
PMID- 9656084
TI - [Preoperative evaluation of severe aortic stenosis by Doppler echocardiography
and hemodynamics].
AB - Several diagnostic tools have been used in the evaluation of the severity
transvalvular gradient and aortic valve area. The advances in cardiac
catheterization and Doppler echocardiographic measure these items accurately. We
designed a retrospective, observational open and transversal survey that included
patients with severe aortic stenosis that required transseptal cardiac
catheterization. Their echocardiographic and hemodynamic studies were reviewed.
From January 1991 to December 1996 we studied 30 patient from a population of
256. All of them with severe aortic stenosis. There were 17 males and 13 females
with an age range from 32 a 71 years. RESULTS: the transvalvular gradient
measured by catheterization vs. Doppler echocardiogram was 98.80 +/- 37.29 mmHg
vs. 96.63 +/- 38.64 mmHg respectively P = 0.84. The valvular area measured by
catheterization vs Doppler echocardiographic 0.63 +/- 0.17 cm2 vs 0.62 +/- 0.15
cm2 respectively P = 0.63. There was not difference in the gradients using these
two methods. We conclude that patients with severe aortic stenosis could be
referred to surgical procedure without the need of cardiac catheterization if no
concurrent coronary disease is suspected.
PMID- 9656085
TI - [Cardiac tamponade in newborn infants with central venous catheter receiving
parenteral nutrition].
AB - OBJECTIVE: To alert about an unusual and poorly informed entity, with high
mortality. That should be considered in critically ill neonates with central
venous catheter and parenteral nutrition, in order to establish early diagnosis
and treatment. CASE REPORT: Two neonates, one born at term and the other
premature, with central venous catheter and parenteral nutrition. They had sudden
unexplained hypotension and signs of decompensation and death secondary to
cardiac tamponade. DISCUSSION: Cardiac tamponade secondary to central venous
catheter is an unusual entity seldom discussed in the literature. The estimated
incidence is 0.3 to 2% with a 74 to 100% mortality. It must be suspected and
diagnosed early in order to decrease the mortality.
PMID- 9656086
TI - Low molecular weight heparins in clinical practice: unsolved or partially solved
problems.
AB - Low molecular weight heparins (LMWH) have been shown, in recent years, to be at
least as effective as standard heparin (SH) in the prophylaxis and treatment of
venous thrombosis. In spite of several studies there are still some unsolved
problems to be dealt with. These may be summarized along the following lines: 1)
Side effect; 2) Use in pregnancy; 3) Role in arterial thrombosis; 4) Use in
severe deep venous thrombosis; 5) Use for home treatment; 6) Effect on cancer
related mortality; 7) Standardization of preparations; 8) Dosage uncertainties;
9) Long term treatment. The two most important aspects are those pertaining to
the potential use in arterial thrombosis and the possibility of home treatment of
selected patients with venous thromboembolism. A few studies now indicate that
LMWH may play an important role in several arterial thrombosis (coronary disease,
ischemic stroke, etc). As far as the indications for home treatment are
concerned, recent studies have given a positive answer. However, rather than home
treatment it would be more appropriate to refer to early discharge from the
hospital. The overall impression is that LMWH may represent an important progress
in the management and prophylaxis of thrombotic disease.
PMID- 9656087
TI - [Methodology in clinical research: its role in medical education].
PMID- 9656089
TI - Computer-administered rating scales for social anxiety in a clinical drug trial.
AB - Computer-administered versions of two clinician-administered symptom rating
scales for social anxiety (the Liebowitz Social Anxiety Scale [LSAS] and the
Brief Social Phobia Scale [BSPS]) and one paper-and-pencil scale (the Fear
Questionnaire) were developed and utilized in a clinical trial for social phobia.
The reliability and validity of the computer versions were examined, as were
their equivalence to the traditional versions. Correlations between the computer
and original versions were high at baseline, and remained high throughout the
study. The internal consistency reliability of the computer scales was also high,
and almost identical to the original versions. Mean score differences between
computer and original versions were not significant at baseline, and no
significant differences were found between computer and traditional versions on
the amount of change detected from baseline to endpoint. Seventy-seven percent of
subjects felt that the computer did not interfere with their visit at baseline
and a plurality (36%) preferred the computer, with 30% preferring the clinician
and 34% having no preference. By the end of the study, the plurality (41%) had no
preference, with 27% preferring the computer and 32% preferring the clinician.
Results support the use of these computer-administered symptom rating scales of
social anxiety as a viable alternative to the clinician-administered versions
with this subset of patients, which should offer researchers and clinicians a
reliable and cost-effective method for evaluating social phobia.
PMID- 9656088
TI - [William Osler and angina pectoris: still prevailing concepts].
PMID- 9656090
TI - Simple phobia as a comorbid anxiety disorder.
AB - This study sought to describe clinical and demographic characteristics
differentiating patients with DSM-III-R simple phobias comorbid with one or more
of five DSM-III-R index anxiety disorders as compared with those with the index
diagnoses alone. From 711 subjects participating in a multicenter, longitudinal,
naturalistic study of anxiety disorders, 115 subjects with comorbid simple
phobias were compared with 596 subjects without simple phobias in terms of
demographic data, comorbidity with other disorders, somatic and psychosocial
treatment received, and quality of life. In addition, episode characteristics,
types of simple phobias found, and course of illness were specified. Subjects
with simple phobias had more additional comorbid anxiety disorders by history
than did those without. Mean length of intake episode was 22.43 years and
severity was typically moderate. Fears of heights and animals were the most
commonly represented simple phobias. Subjects with uncomplicated panic disorder
were less likely to have comorbid simple phobias than were subjects with other
index diagnoses, and subjects with simple phobia were more likely to have
comorbid posttraumatic stress disorder than were these without simple phobia.
Subjects with and without simple phobias did not differ by somatic or
psychosocial treatment received or in terms of quality of life. Simple phobia
appeared in this study to be a chronic illness of moderate severity for which
behavioral treatment methods of recognized efficacy were not being frequently
utilized. Uncomplicated panic disorder may reflect some type of resistance to
phobia development.
PMID- 9656091
TI - Lifetime patterns of social phobia: a retrospective study of the course of social
phobia in a nonclinical population.
AB - This study describes the natural course of social phobia as recalled by a sample
of nonclinical subjects and explores, using qualitative research methods,
perceived risk factors and factors that may cause changes in its course. Thirty
nine respondents with a lifetime diagnosis of social phobia were interviewed
using a semistructured interview schedule based on DSM-IV criteria. Four main
lifetime patterns emerged: a slight worsening of social phobic symptoms over
time, no change, slight improvement and complete remission. Thirty-eight percent
of the sample was in remission at the time of interview. The mean age of onset
was 12.8 +/- 4.1 years. The average duration of illness was 29.0 +/- 12.7 years.
Factors perceived by respondents to precipitate social phobia, using contract
analysis, were family and school environment, onset of adolescence, low self
esteem, temperament and poverty. Factors perceived to improve symptoms were
building self-esteem, exposure, determination, maturity and counseling. Factors
perceived to worsen symptoms were avoidance, exposure to negative attention and
comorbid disorders.
PMID- 9656092
TI - Comparison of sodium lactate-induced panic symptoms between panic disorder and
posttraumatic stress disorder.
PMID- 9656093
TI - Low dose selegiline (L-Deprenyl) in social phobia.
PMID- 9656094
TI - Caffeine use and plasma concentrations in psychiatric outpatients.
PMID- 9656095
TI - Medication treatments for panic disorder and social phobia.
AB - In this Research Review, several recent clinical trials in panic disorder and
social phobia are reviewed. First, two social phobia studies which used the
monoamine oxidase type A inhibitors brofaromine and moclobemide are considered.
Then, three panic disorder studies which used clonazepam, clomipramine or
paroxetine, and citalopram are examined. These studies serve to strengthen the
empirical research base regarding which treatments are useful in these disorders.
PMID- 9656096
TI - Intrusive thought in obsessive-compulsive disorder: appraisal differences.
PMID- 9656097
TI - Working on the railroad: reactions to traumatic and stressful events.
PMID- 9656098
TI - Possible inhibition of family PTSD symptoms by alcohol intoxication.
PMID- 9656099
TI - [Advanced prostate cancer with normal serum prostate-specific antigen values].
AB - Although prostate-specific antigen (PSA) is a valuable marker of prostate cancer,
some untreated patients with advanced prostate cancer have normal PSA values.
Over a period of 5 years, we reviewed pretreatment serum PSA levels in 131
patients with advanced prostate cancer (stages C and D). Ten patients (7.6%) had
normal PSA values. The histological type of prostate cancer associated with
normal PSA values was variable and the prognosis was not so poor. Immunostaining
for PSA was performed on the resected prostate tissue of the 10 patients. PSA
staining was positive in 5 cases, negative in 3 cases, and equivocal in the
remaining 2 cases. In conclusion, PSA is not always useful, especially for
following patients with normal PSA values.
PMID- 9656100
TI - Free-to-total prostate specific antigen ratio in clinical staging of prostate
cancer.
AB - The value of the free-to-total serum prostate-specific antigen (f/t PSA) ratio
was compared with that of the total prostate specific antigen (tPSA) value for
the prediction of clinical stage in patients with prostate cancer. The f/t PSA
ratio was obtained from the frozen sera of 56 untreated patients with
histologically proven BPH and 78 patients with prostate cancer. The clinical
stage was organ-confined in 36, locally advanced in 20 and metastatic in 22
patients. Serum levels of free PSA (fPSA) and tPSA were determined using a
chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing
the fPSA value by the tPSA value and was compared with tPSA and fPSA in the
correlation with clinical stage via the Spearman rank correlation test. Patients
with prostate cancer had a significantly lower f/t PSA ratio than patients with
BPH. The f/t PSA ratio did not differ between patients with clinically localized
and metastatic cancer. tPSA and fPSA reflected the clinical stage and the extent
of bone metastasis more accurately than the f/t PSA ratio. The extent of bone
metastasis had no effect on the PSA ratio. The f/t PSA ratio had no additional
value in clinical staging compared to tPSA. Our study suggests that the f/t PSA
ratio does not reflect tumor load.
PMID- 9656102
TI - [A case of renal cell carcinoma with metastasis in clivus presenting as
diplopia].
AB - We report a rare case of renal cell carcinoma presenting as diplopia which was
caused by a metastasis to the clivus. A 58-year-old man was admitted to our
hospital with the chief complaint of diplopia. Head magnetic resonance imaging
showed a mass in the clivus accompanied by bone destruction. Metastatic tumor to
the skull base was suspected. Further examinations for the primary lesion
revealed left renal cell carcinoma. He was relieved of diplopia by radiotherapy
to the clivus and subsequently underwent left radical nephrectomy.
PMID- 9656101
TI - [High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT)
For advanced testicular cancer].
AB - Five patients with metastatic testicular cancer of advanced extent according to
the Indiana University criteria were enrolled into this study. All tumors were
non-pretreated non-seminomas. Initially all patients were treated with standard
dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two
cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the
five patients showed a good response to VIP and subsequently achieved a
pathological complete response (pCR) following surgical resection of residual
masses after 3 or 5 courses of VIP. However, they suffered from severe
myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT)
following the final course of VIP. The remaining three patients unlikely to be
cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10
g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400
mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial
response (PR) with marker-negative and two PR with marker-positive. Residual
masses were removed in all three patients and viable tumor cells were found in
two. Of the five patients enrolled, four patients (80%) remain disease-free with
minimal follow-up of 20 months, and the remaining one died of cancer 10 months
after PBSCT. No serious side effects or complications were encountered. This
study shows that standard dose induction therapy of VIP followed by early salvage
chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the
treatment of advanced poor-risk testicular cancer.
PMID- 9656103
TI - [Laparoscopic fenestration of lymphocele after renal transplantation: report of
two cases].
AB - Lymphocele after renal transplantation is a complication that often requires
surgical treatment. We performed laparoscopic drainage for the postoperative
lymphocele in two renal transplantation patients. The patients were suffering
from perineal discomfort and urinary frequency due to the lymphocele after the
renal transplantation. Percutaneous catheter drainages and injections of tissue
sclerosing agents such as povidone-iodine solution and tetracycline were not
effective. Then fenestration of the lymphocele by laparoscopic technique was
done. This procedure made the lymphatic fluid free from the lymphocele in the
retroperitoneal space to the peritoneal cavity following creation of a peritoneal
window. There were no apparent complications. The patients were free from
symptoms and had no relapse 10 months after the operation. We report the
procedure and the results of the laparoscopic fenestration.
PMID- 9656104
TI - [Successful treatment with end-to-end ureteral anastomosis for ureteral avulsion
caused by abdominal blunt trauma: a case report].
AB - Avulsion of ureter without renal injury is rarely caused by blunt trauma, only 28
cases having been reported in Japan. A 33-year-old male was admitted to our
hospital 1 month after blunt abdominal trauma at work. He complained of left
flank pain and macroscopic hematuria. Under the suspicion of renal or ureteral
injury, drip infusion urography and abdominal computerized tomography revealed an
extravasation from the left upper ureter and urinoma formation in the
retroperitoneal cavity. In order to reduce the inflammation, the urinoma was
drained. The retrograde pyelogram revealed complete obstruction at the left upper
ureter, 20 cm from the left ureteral orifice. Urinary tract reconstruction, end
to-end ureteral anastomosis, was performed under the diagnosis of left ureteral
avulsion. Drip infusion urography revealed normal ureteral healing without
stricture formation at 2 years after reconstruction.
PMID- 9656105
TI - [Retrovesical leiomyoma: a case report].
AB - A 41-year-old woman was admitted to our hospital with the chief complaint of
difficulty of urination during the previous 2 years. Physical examinations
revealed a smooth round mass of about 6 cm in diameter at the vaginal anterior
wall. DIP and MRI showed a retrovesical tumor which was composed of benign
leiomyoma, according to the transvaginal needle biopsy report. The retrovesical
tumor was excised by the transvaginal approach. The tumor, 7 x 6 x 4 cm in size
and 109 g in weight, was histologically diagnosed as leiomyoma. This is the 21st
case of retrovesical leiomyoma reported in the literature in Japan.
PMID- 9656106
TI - [A case of endometrioid carcinoma of the prostate].
AB - A case of endometrioid carcinoma of the prostate is reported. A 64-year-old man
was admitted to our department with initial macrohematuria and dysuria. The
transrectal ultrasonogram showed remarkable prostatic hypertrophy and the serum
level of both prostatic specific antigen (PSA) and prostatic acid phosphatase
(PAP) ranged within normal limits. Urethrocystographical and cystoscopical
findings indicated prostatic hypertrophy with elongation of prostatic urethra and
mild trabeculation of bladder wall. During transurethral resection of the
prostate, papillary tumor was accidentally found in the left lobe near the
vermontanum. Histopathological examination revealed adenocarcinoma of the
prostatic urethra and the tumor displayed no immunoreactivity for PSA or PAP.
Under diagnosis of prostatic urethral cancer total cystoprostatectomy and
urethrectomy were performed and ileal conduit was constructed for urinary
diversion. As intraductal papillae and complex ramifying glands were
histopathologically confirmed in the specimen and the immunohistochemical
staining showed positivity of PSA and PAP, the tumor was diagnosed as
endometrioid carcinoma of the prostate.
PMID- 9656107
TI - [The impact of rejection episodes during acute tubular necrosis--diagnosis and
allograft outcome after cadaveric renal transplants].
AB - Diagnosis of acute rejection (AR) is difficult during acute tubular necrosis
(ATN), and a delay of rejection treatment could result in negative impacts on the
renal transplant outcome. At our center, 68 cadaveric kidneys were transplanted
during the past 7 years. The 1-, 3- and 5-year graft survival rates were 95.4%,
93.8% and 81.4%, respectively. After the transplants, 16 patients had immediate
graft function (G-I), 51 patients experienced ATN for 12.0 +/- 9.3 days, and one
patient had a non-functioning graft due to diffuse arteriolar thrombosis caused
by DIC in the donor. During ATN, 41 patients had no rejection episodes (G-II) and
10 patients had ARs (G-III). Nine patients were treated with bolus steroid and
one with steroid and OKT-3. Although scintigraphic and sonographic examinations
were routinely employed, only the histopathological findings of needle biopsies
were helpful for the diagnosis of AR during ATN. When the transplant outcome was
compared, the serum creatinene level was highest in G-III and lowest in G-I (1.48
vs 1.06 mg/dl, p < 0.05). The posttransplant ATN period was also longer in G-III
compared to G-II (23.9 vs 9.1 days, p < 0.005). The 5-year graft survival rate
was 85.2% in G-I, 88.0% in G-II and 59.3% in G-III. We conclude that routine
serial renal biopsies should be scheduled when ATN develops after the cadaveric
renal transplant, since only the histopathological diagnosis is reliable during
ATN.
PMID- 9656108
TI - [The treatment and prognosis of acute late rejection after kidney
transplantation].
AB - To examine the acute late rejection episodes (ALR) occurring 4 months after
kidney transplantation, 330 cadaver kidney transplant recipients who were
operated on between 1982 and 1996 and immunosuppressed by cyclosporine or
tacrolimus were analyzed. In 213 recipients who were followed up for 5 years or
longer, the frequency of ALR without an acute early rejection (AER) was 14% and
ALR with AER was 16%, respectively. ALR was the strongest deteriorating factor
for graft survival at the chronic stage. Judging from the renal function 1 month
after an ALR episode, the complete and partial response rates were 22% and 62%
with steroid treatment and 16% and 58% with DSG treatment, respectively. The 5
year graft survival after the treatment was 20% with steroid treatment and 45%
with DSG treatment. Although the intensity of the rejection classified based on
the Banff grading system was the strongest factor affecting the graft survival,
the multivariate analysis by Cox proportional hazard model for non-pathological
factors revealed that urine protein and hypertension 1 month before the episodes
may also be important prognostic factors. The body weight of recipient (> 55 kg)
and donor age (> 55 y.o) were slightly correlated to the graft prognosis. Due to
incomplete immuno-suppressive methods for acute late rejection, the conservative
nephron sparing policy after a rejection episode is inevitable to obtain better
graft survival at the chronic stage.
PMID- 9656109
TI - [Current topics of the rejection pathology in human renal allografts].
AB - The topics of renal allograft pathology; validation of the Banff classification
and a new criterion for chronic rejection are reviewed. Although the clinico
pathologic utility of the Banff classification is remarkably high in acute
rejection, the Banff scheme is still incomplete. The severity of rejection based
on the Banff schema well correlated with the deterioration of graft function and
also with reversibility of the graft function. Grade III acute rejection in the
Banff schema suggested poor graft function, while grade IIb acute rejection could
be cured by rejection therapy in the CyA era. The morphological characteristics
of chronic rejections in renal allografts become milder and less specific in the
CyA era. The differentiation of chronic rejection of immunologic origin from
other conditions leading to renal scarring remains one of the major problems in
renal allograft biopsy interpretation. Chronic CyA nephrotoxicity and/or
glomerulonephritis frequently accompany chronic rejection. Electron microscopic
peritubular capillary basement membrane lesion (MSPTC) was a sensitive indicator
for chronic rejection of immunologic origin as well as glomerular capillary
lesions. The negative MSPTC in the patients with chronic rejection suggest that
the deterioration of the graft function is probably non-immunologic in origin.
PMID- 9656110
TI - [Indication for the steroid therapy for acute rejection].
AB - Between January 1, 1986 and March 31, 1997, 103 kidney transplantations were
performed at our institution. Seventy-nine grafts were from living related
donors; one was from a living unrelated donor; 23 were from cadaveric donors.
Basic immunosuppression consisted of cyclosporin (CYA), azathioprine (AZ) and
methylprednisolone (MP). Twenty of these grafts (14.9%) developed steroid
resistant rejection (SRR). The 5-year graft survival rate of patients with SRR
(57.9%) was lower than that with no rejection (92.9%) and steroid responded
rejection ( 85.6%). (p = 0.002) Treatment methods of SRR were methylprednisolone
pulse (n = 5), plasma exchange (n = 7) and others (n = 8) such as, OKT 3, 15
deoxyspergualin, anti-thymocyte globulin, Tacrolimus rescue and cyclosporin
rescue. No significant differences could be seen on the 5-year graft survival
between the 3 groups. We reviewed 9 episodes of acute rejection, and compared the
Banff classification with the degree of reversibility of rejection. Of the 9
biopsies examined, 5 were classified as borderline change, 2 had mild rejection
(grade I), 2 had moderate rejection (grade II), 1 had severe rejection (grade
III). Complete reversal of rejection by steroids was observed in only 3 patients;
2 were borderline and one was grade II.
PMID- 9656111
TI - [Histopathological findings and clinical effects for acute rejections].
AB - We reviewed 115 cases of acute rejection following renal transplantation. All
cases were diagnosed after graft biopsy, and showed histopathological evidence of
acute rejection. They were treated with administration of OKT3, 15
deoxyspergualin (DSG), anti-lymphocyte globulin (ALG) or methylprednisolone (MP).
All rejections were histopathologically classified according to the Banff working
classification. The clinical effects of each drug were evaluated both at 1 month
and 1 year following the therapy for rejection, by measurement of serum
creatinine level. The effective rate both at 1 month and 1 year was related with
the Banff working classification ( p < 0.0001). At 1 month after treatment, there
were no significant differences between the OKT3, DSG or ALG group and MP group
in cases of borderline change and AR grade I. In cases of grade II and grade III,
a significant difference was observed between the OKT3 or ALG group and MP group
(p < 0.05). The DSG group showed a slightly better outcome than the MP group,
although the difference was not significant. In conclusion, the Banff schema is
shown to be valid for classification of acute renal allograft rejection, and it
is necessary to determine the treatment for acute rejection according to
histopathological classification.
PMID- 9656112
TI - [Is tacrolimus effective for ongoing renal allograft rejection?].
AB - Tacrolimus has already gained a high reputation as an induction-maintenance
immunosuppressive therapy after kidney transplantation. Recently, it is being
used as rescue therapy against rejection, and its effectiveness also appears to
have been established to some extent. In this study, we evaluated the efficacy of
Tacrolimus rescue therapy at 4 institutions in the Kinki District. The subjects
were 19 patients treated with Tacrolimus against rejection observed during
immunosuppressive therapy using cyclosporin. Evaluation was made by classifying
the patients into 6 with acute rejection that occurred within 3 months after
transplantation (AR), 4 with late onset acute rejection that developed more than
3 months after operation (LAR), and 9 patients with chronic rejection (CR). In
the AR group, many patients received combination therapy at the introduction of
Tacrolimus, and the long-term outcome was satisfactory. Tacrolimus was effective
in 2 (50%) of the 4 patients in the LAR group. The trough levels of Tacrolimus at
its introduction were 10-15 ng/ml in the AR and LAR groups. Deterioration of the
transplanted kidney function was prevented in 3 (50%) out of 6 patients in the CR
group observed for less than 1 year, but it deteriorated in all 3 patients
observed for 1 year or longer. The trough levels of tacrolimus at its
introduction were 5-10 ng/ml in many patients in the CR group. The rescue therapy
using Tacrolimus was effective against acute rejection but further follow-up is
considered to be needed to evaluate its efficacy against chronic rejection.
PMID- 9656113
TI - Isolated necrotizing arteritis of the female genital tract: a clinicopathologic
and immunohistochemical study of 11 cases.
AB - Isolated necrotizing arteritis (INA) of the polyarteritis-nodosa type localized
to the female genital tract is rare. Approximately 30 case reports have been
published to date. Eleven additional patients are described here, all with a
favorable follow-up. INA is usually localized in the uterine cervix, but, when
multifocal lesions are present, the latter is almost always involved. Patients
most frequently report menorrhagia or postmenopausal bleeding. With
immunohistochemical studies, immune-complex deposits (IgM, IgG, and C'3) in 7 of
11 patients with INA of the female genital tract were demonstrated for the first
time. The inflammatory cells were composed mainly of T-lymphocytes with
macrophages and scarce B-lymphocytes also present. These results suggest that INA
is primarily an immune complex-mediated disease, implicating humoral and cellular
mediator systems. Possible pathogenetic factors of INA are immune complex
mediated hypersensitivity reactions to drugs, foreign materials (after cone
biopsy or curettage), and cancers, or an autoimmune reaction against constituents
of the vessel walls caused by tissue injury after local surgical intervention
through in situ immune-complex formation.
PMID- 9656114
TI - Do mucin-secreting squamous cell carcinomas of the uterine cervix metastasize
more frequently to pelvic lymph nodes? A case-control study?
AB - Twenty-nine patients with stage IB/IIA squamous cell carcinoma of the uterine
cervix who had positive pelvic nodes were matched with 29 cases of node-negative
squamous cell carcinoma by depth of invasion and lymphovascular space invasion.
By multivariate analysis, these criteria independently predicted pelvic node
metastases. Intracellular mucin, demonstrated by alcian-blue staining at pH 2.5,
was noted in 21 of the 58 patients (36%). The frequency of mucin-positive tumors
was not significantly different between the patients and their controls (38
versus 34%, p = 0.78), nor was the degree of positivity. These results suggest
that, although a substantial proportion of squamous cell carcinomas exhibit mucin
secretion, patients with these tumors are not at increased risk for pelvic node
metastases. We therefore do not recommend routine mucin staining in cervical
squamous cell carcinomas.
PMID- 9656115
TI - Ulex Europaeus lectin and anti-CD31 staining in squamous cell carcinoma of the
uterine cervix: potential prognostic markers.
AB - Seventy-five squamous cell carcinomas of the uterine cervix and 10 controls were
stained for Ulex Europaeus lectin 1 (UEA-1) and anti-CD31, and the results were
analyzed with respect to patient age, clinical stage, tumor grade, and survival
during a follow-up period of 1 to 13 years. The patients' mean age at the time of
diagnosis was 47.8 years (range, 27 to 83). Seventeen patients died of disease, 2
had disease recurrence, and 51 patients remained free of disease; 5 patients were
lost to follow-up. Twenty-eight cases (37.3%) showed focal membranous staining
for UEA-1 and 9 cases (12%) showed a diffuse pattern; 38 cases (50.7%) were UEA-1
negative. Poor survival was related to diffuse membranous UEA-1 immunoreactivity
(p = 0.02), age (p = 0.014), grade (p = 0.02), and stage (p = 0.0002). CD31
positive neoplastic cells displayed a cytoplasmic pattern. Fifteen cases (20%)
had diffuse staining and another 15 (20%) stained focally; 45 cases (60%) were
CD31-negative. The adjacent nonneoplastic epithelium and all 10 controls were
uniformly negative for CD31. Variable staining of the endocervical epithelium and
weak or negative staining of ectocervical epithelium for UEA-1 were observed.
However, the epithelium in all controls was negative for UEA-1. Poor survival was
related to both focal and diffuse staining for CD31 (p = 0.01 and p = 0.03,
respectively). Staining by both UEA-1 and anti-CD31 retained its correlation with
survival after exclusion of stage la tumors.
PMID- 9656116
TI - Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of
a neoplasm with morphology often different from its counterpart in the corpus.
AB - Malignant mullerian mixed tumors (MMMTs) of the uterine cervix are rare; less
than 30 cases have been reported in the literature and only 14 have been
described in detail. As a result, the clinical and pathologic features of these
tumors are not well characterized. The clinicopathologic features of nine
cervical MMMTs (all cases referred because of problems in differential diagnosis)
are reported here and the literature on the previously described cases is
reviewed. The patients ranged in age from 23 to 87 (mean 65) years. The initial
manifestations were mainly vaginal bleeding or spotting or, less commonly, an
abnormal Pap smear. All of the patients had a cervical mass on examination. Of
the eight patients for whom staging information was available, seven were stage
Ib and one was stage II. Treatment in six patients was hysterectomy with
lymphadenectomy in five; postoperative radiation therapy, chemotherapy, or both
were given to two of these patients. The remaining three patients were treated by
local excision (with lymphadenectomy in one) followed by radiation therapy,
chemotherapy, or both in two. Follow-up, available for seven patients, revealed
recurrent pelvic tumor in two patients at 1.6 and 3.0 years, respectively; the
former patient died from tumor at 3.5 years whereas the latter was alive with
tumor at 4.5 years. Another patient was well for II years but died 13 years
postoperatively from colonic adenocarcinoma. Four other patients were alive with
no evidence of tumor at postoperative intervals of less than 2 years. Gross
examination revealed polypoid or pedunculated masses 1.1 to 10.0 cm in maximal
dimension that invaded the cervical wall in 50% of the hysterectomy specimens. On
microscopic examination, three tumors contained a predominant or exclusive
epithelial component of basaloid carcinoma, two contained squamous cell
carcinoma, and four contained adenocarcinoma (endometrioid in three and
nonspecific in one). In seven tumors, the sarcomatous component was homologous,
usually resembling fibrosarcoma or endometrial stromal sarcoma; in four of these
tumors, myxoid change was prominent. Two tumors contained heterologous
sarcomatous elements. In three patients, a pure carcinoma abutted the MMMT: an
adenoid basal carcinoma in two (with a minor component of in situ and invasive
squamous cell carcinoma in each) and an endometrioid endocervical adenocarcinoma
in one. These findings, combined with analysis of the previously reported cases,
indicate that cervical MMMTs, compared to their counterparts in the corpus, are
more commonly confined to the uterus at presentation, may have a better
prognosis, and frequently have a nonglandular epithelial component.
PMID- 9656117
TI - Malignant schwannoma of the uterine cervix: a study of three cases.
AB - Pure sarcomas of the uterine cervix are rare; most of those reported have been
leiomyosarcomas or rhabdomyosarcomas. Minimal data exists on malignant nerve
sheath tumors in this site; only one typical example and one melanocytic example
have been reported. We report three additional examples here in three patients
25, 65, and 73 years of age. The two older patients had vaginal bleeding and
underwent hysterectomy as initial treatment. The youngest patient initially
underwent only polypectomy. The tumors were 1.3, 4.4, and 5.0 cm in greatest
dimension. The tumors were red-grey to white: two were polypoid and the third was
ulcerated. The dominant microscopic appearance was that of cellular fascicles of
spindle cells with hyperchromatic nuclei and eosinophilic cytoplasm. However,
hypocellular areas were striking in each case; the hypocellular areas were
fibromatous in two tumors and two had areas with a myxoid stroma (prominent in
one). One tumor focally had cellular aggregates with a swirling pattern within a
hypocellular background. Epithelioid foci in which tumor cells were rounded with
conspicuous eosinophilic cytoplasm were focally prominent in one case. Mitoses
were readily identified in each case. All three tumors were positive for S-100
protein and vimentin and negative for cytokeratin. HMB-45, and desmin. One case
is recent and one patient had multiple metastases in the abdomen 2 years after
hysterectomy. The patient treated initially by polypectomy underwent repeat local
excision, followed by cone biopsy with positive margins, and then hysterectomy.
She is clinically free of disease 15 months after diagnosis. Although the
diagnosis of malignant schwannoma was suggested by the histologic features of the
tumors, other diagnoses were entertained and immunohistochemistry was crucial in
confirming the diagnosis. These tumors should be distinguished from other
malignant spindle cell tumors of the cervix, such as leiomyosarcoma, endocervical
"stromal sarcoma," and spindle cell melanoma, so their features, behavior, and
optimal therapy can be further delineated.
PMID- 9656118
TI - Leiomyomas of the uterine cervix: a study of frequency.
AB - Leiomyomas of the cervix are said to be uncommon. To establish their frequency,
661 consecutive total hysterectomy specimens were examined macroscopically and
microscopically. Myometrial leiomyomas were present in 427 uteri (64.6%) but
cervical leiomyoma were present in only 4 (0.6%). One of these was 6 mm in
diameter and occurred in a uterus without fibroids elsewhere. Only two could have
been considered clinically significant. An additional six cases showed submucous
fibroids of the body of the uterus protruding as a polyp into the endocervical
canal but these were not considered cervical leiomyomas. The conclusion of the
study is that cervical leiomyomas are extremely uncommon.
PMID- 9656119
TI - Immunohistochemical analysis of cell cycle regulatory gene products in normal
trophoblast and placental site trophoblastic tumor.
AB - Intermediate trophoblast (IT) rarely gives rise to a placental site trophoblastic
tumor (PSTT) To examine the different growth mechanisms present in normal and
neoplastic IT, the expression of cell cycle regulatory molecules was compared at
normal implantation sites and in PSTTs. Normal implantation sites in early
gestation (19 patients) and PSTTs (6 patients) were immunohistochemically studied
using antibodies against cytokeratin, human chorionic gonadotropin, and human
placental lactogen to identify IT, and antibodies against Ki-67, cyclins (A, B,
D1, and E), cyclin-dependent kinases (cdks), and p53 to investigate the
proliferative activity of the trophoblast. Marked proliferative activity was
observed in the trophoblast of the cell columns. Normal IT exhibited a very low
labeling index for Ki-67, with negative expression for cdks and cyclins, except
for cyclins B and E. The tumor cells of PSTT exhibited a high labeling index for
Ki-67 with positive expression for all the cyclins and cdks examined. Expression
of p53 was identified in tumor cells of PSTTs and the distribution of p53
positive cells correlated topographically with that of the cyclin A-positive
cells. The transformed IT of PSTT has high proliferative activity with an
abnormal expression of cell cycle regulatory molecules, which is not observed in
normal IT.
PMID- 9656120
TI - Hepatic (hepatocellular) adenoma of the placenta: a study of four cases.
AB - Hepatic (hepatocellular) adenoma of the placenta is an extremely rare
nontrophoblastic placental lesion of disputed histogenesis, four examples of
which were diagnosed over a 10-year period. The lesions, which were incidental
findings in women 21 to 30 years of age (mean, 25; median, 24.5), ranged from 0.3
to 1.0 cm in greatest dimension. Two were found within the villous parenchyma and
two in subchronic locations. On cross section, two examples were tan to dark red
nodules without necrosis or hemorrhagic foci, whereas two were not visible
grossly. The lesions were composed of semidistinct lobules of cords and nests of
polygonal epithelial cells resembling fetal liver. Extramedullary hematopoiesis
was a constant feature. The lesional cells contained glycogen and were
immunoreactive for cytokeratin, alpha-fetoprotein, alpha-1-antitrypsin, and
carcinoembryonic antigen. Although the histogenesis of these lesions remains
uncertain, an origin from displaced yolk sac elements with hepatocytic
differentiation is the most likely hypothesis. It is important to distinguish
hepatic adenoma of the placenta from placental cell island, heterotopic
adrenocortical nodule, chorangioma, and placental metastasis of maternal and
fetal malignancies.
PMID- 9656121
TI - Primary carcinoma of the fallopian tube: comparative genomic hybridization
reveals high genetic instability and a specific, recurring pattern of chromosomal
aberrations.
AB - Primary fallopian tube carcinoma (PFTC) is a rare and highly aggressive tumor.
Twelve cases of PFTC (stages IA to IV) were analyzed by comparative genomic
hybridization. The most consistent DNA gain was mapped to chromosome arm 3q in 11
of 12 cases. In six cases, the gain of 3q was present as a high level copy number
increase (amplification) with a consensus region mapped to 3q26.2-qter. In the 12
cases, other frequent gains were located on chromosome arms 1q (in 11 cases), 2q
(in 10), 7q (in 9), 8q (in 9), 5p (in 8), 6p (in 7), 12p (in 7), and 14q (in 6).
Frequent copy number losses occurred on chromosome arms 16q (in 8 cases), 22q
(in7), 6q (in 6). 8p (in 6), 18q (in 6), Xq (in 6), 1p (in 5), and 17p (in 5).
All chromosomes were involved in chromosomal aberrations and the average number
of copy alterations per case was 19.7. None of the 12 carcinomas revealed the
presence of human papillomavirus (HPV) genomes. All of the cases exhibited crude
aneuploidy. Strong p53 immunoreactivity could be observed in 10 of 12 cases while
p21/WAF1 expression was low or undetectable. These results indicate that PFTC is
a genomically highly unstable cancer, an observation that is in agreement with
the poor prognosis associated with this tumor. A high frequency of 3q-gains has
also been observed in HPV-related carcinomas of the uterine cervix. However, none
of the PFTC was HPV related, suggesting that the 3q-gain is independent from HPV
DNA.
PMID- 9656122
TI - Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in
ovarian surface epithelial tumors.
AB - Cell survival may be enhanced in tumors by the inhibition of apoptosis, which
allows tumor promotors to exert their effects. The bcl-2 related genes have been
shown to contribute to either the inhibition or induction of apoptosis in a
variety of neoplasms; therefore, it was hypothesized that the expression of these
genes might contribute to malignant transformation in ovarian surface epithelial
tumors. The expression of bcl-2 family proteins was investigated in 28 ovarian
surface epithelial tumors, including serous and mucinous benign, borderline, and
malignant tumors by immunohistochemical staining with antibodies to bcl-2, bax,
bcl-X, and mcl-1 proteins. Staining intensity was scored on a 1+ to 3+ scale and
the benign, borderline, and malignant tumors were compared. Significantly less
immunoreactive bcl-2 and bcl-X proteins were present in malignant serous tumors
compared to their benign counterparts. No difference was seen in immunostaining
for bax or mcl-1 when benign, borderline, or malignant serous tumors were
compared. In the mucinous tumors, no differences were seen in immunostaining for
any of the bcl-2 family proteins between tumor types. The loss of expression of
the antiapoptotic proto-oncogenes bcl-2 or bcl-X in serous carcinomas compared to
benign serous tumors, together with previous demonstrations that the presence of
bcl-2 in ovarian surface epithelial cancers is a favorable prognostic indicator,
suggests that bcl-2 and bcl-X have biological functions in the ovary other than
inducing apoptosis, acting instead as tumor suppressor proteins.
PMID- 9656123
TI - Histopathologic and immunohistochemical study of steroidogenic cells in the
stroma of ovarian tumors.
AB - The presence of steroidogenic or enzymatically active stromal cells in ovarian
tumors can lead to various endocrine manifestations by the overproduction of sex
steroids. We studied the clinicopathologic and immunohistochemical features of
histologically identified steroid-type cells or enzymatically active cells in the
stroma of ovarian lesions. Among 1,249 ovarian tumors or tumorlike lesions,
steroid cells were histologically identified in the stroma in 32 ovarian
neoplasms, of which 29 were mucinous cystadenomas. The cells were Leydig- or
hilus-type cells in 4 of the tumors and were lutein-type cells in the remaining
28. None of the 32 tumors were immuno-reactive for human chorionic gonadotropin
or luteinizing hormone. Lutein-like steroid cells were intermingled with spindle
shaped stromal cells and capillaries, while Leydig-type cells were more often
associated with dilated vessels. The transcription factor of steroidogenesis,
adrenal 4-binding protein (Ad4BP), was present in nearly all steroid-type stromal
cells. However, steroidogenic enzymes, 17 alpha-hydroxylase (C17) and 3 beta
hydroxysteroid dehydrogenase (3 beta SD), were expressed only in 10 of 15 cases
of histologically identified steroid cells. Steroid cells in which Ad4BP but not
C17 or 3 beta HSD were expressed were all lutein-type. Aromatase was rarely
detected in lutein-and Leydig-type cells. The presence of morphologically
identified steroid cells does not necessarily indicate expression within these
cells of steroidogenic enzymes, a finding that merits further attention.
PMID- 9656124
TI - Ovarian endometrioid carcinomas simulating sex cord-stromal tumors: a study using
inhibin and cytokeratin 7.
AB - We have investigated the use of inhibin and cytokeratin-7 (CK-7) in
distinguishing endometrioid ovarian carcinomas (both typical and sex cord-like)
form granulosa cell and Sertoli cell-containing ovarian tumors.
Immunohistochemical staining with inhibin, CK-7, and epithelial membrane antigen
(EMA) was performed on 6 endometrioid carcinomas simulating sex cord-stromal
tumors, 5 typical endometrioid carcinomas, 14 adult granulosa cell tumors
(AGCTs), 3 Sertoli-Leydig cell tumors (SCLTs), and 1 sex cord tumor with annular
tubules (SCTAT). All AGCTs and SLCTs as well as the SCTAT were inhibin-positive.
In contrast, all of the endometrioid carcinomas (both typical and those mimicking
sex cord-stromal tumors) were inhibin-negative. CK-7 expression was not observed
in the granulosa cell tumors and it was noted only in retiform areas in SLCTs.
All 5 typical endometrioid carcinomas and 5 of the 6 sex cord-like endometrioid
carcinomas were CK-7 positive. EMA was positive in all carcinomas but negative in
the SCTAT, AGCTs, and SLCTs. Inhibin can distinguish between sex cord-stromal
tumors (whether granulosa or Sertoli-Leydig type) and endometrioid carcinomas. CK
7 is also helpful in differentiating between AGCTs and most endometrioid
carcinomas, and may also aid in separating SLCTs from sertoliform carcinomas. The
addition of inhibin to an antibody panel is important because it provides a
positively-staining marker for sex cord-derived cells.
PMID- 9656125
TI - Lymphoepitheliomalike carcinoma: an unusual variant of endometrial cancer. A
report of two cases.
AB - Two undifferentiated carcinomas of the endometrium with a prominent inflammatory
reaction that were morphologically similar to nasopharyngeal cancers occurred in
two patients who had postmenopausal bleeding. Tumor cells in both patients were
large with indistinct cytoplasmic borders, vesicular nuclei, and prominent
nucleoli, were arranged in sheets, in groups, or singly, and surrounded by an
intense inflammatory component of lymphocytes, plasma cells, and karyorrhectic
debris. Tumor cells were keratin (AE1/EA3) and epithelial membrane antigen (EMA)
positive and leukocyte common antigen (LCA) negative. All three methods used for
the detection of Epstein Barr virus (EBV) infection were negative. The first
patient (International Federation of Gynecology and Obstetrics [FIGO] stage IVB)
received chemotherapy and is alive and free of disease 9 months after diagnosis.
The second patient (FIGO stage IIIC) received radiation therapy and chemotherapy
6 months after evidence of extensive retroperitoneal disease and died of disease
1 year after diagnosis. Tumors with these histologic features have been
designated as lymphoepitheliomalike carcinomas (LELC) when they occur outside the
nasopharynx. LELC can occur in the endometrium and, in this location, may not be
associated with EBV infection.
PMID- 9656126
TI - Primary extrarenal Wilms' tumor of the uterus presenting as a cervical polyp.
AB - Extrarenal Wilms' tumor is rare in any site, and only three cases arising within
the uterus have been reported. Two of the previous cases were in adolescent
girls, appearing as polypoid vaginal masses, and the third was in a 22-year-old
woman who had menometrorrhagia. An extrarenal Wilms' tumor in an 11-year-old girl
that initially appeared as a 10-cm polyp protruding through the cervix is
described. Triphasic differentiation with mesenchymal stroma showing
rhabdomyoblastic differentiation both morphologically and immunohistochemically
was demonstrated. Epithelial differentiation with focal glomerular
differentiation also was present. Most of the primary tumor and almost the entire
recurrent tumor were composed of blastemal cells. The diagnosis of an extrarenal
Wilms' tumor should be entertained when examining a polypoid tumor of the cervix
or a polypoid mass within the vagina in an adolescent patient.
PMID- 9656127
TI - Recurrent mixed germ cell-sex cord-stromal tumor of the ovary in an adult.
AB - A 32-year-old woman underwent laparotomy and right salpingo-oophorectomy for a
right adnexal mass. Examination of the specimen revealed a 77 g well-encapsulated
tumor that was diagnosed as a mixed germ cell-sex cord-stromal tumor with annular
tubules. Sixty-seven months after an uneventful recovery, a large recurrence was
treated by total abdominal hysterectomy, left salpingo-oophorectomy, removal of
peritoneal implants, lymphadenectomy, omentectomy, and chemotherapy.
Histologically, the neoplasm was identical to the one found in the right ovary.
To our knowledge, no similar case has been previously reported.
PMID- 9656128
TI - Bilateral atypical hyperplasia of the fallopian tube associated with tamoxifen: a
report of two cases.
PMID- 9656129
TI - Error-correction problems in autism: evidence for a monitoring impairment?
AB - With a task involving the launching of missiles at targets, Malenka et al. (1982)
and C. Frith and Done (1989) showed that schizophrenic patients with delusions of
alien control and auditory hallucinations were likely to leave erroneous
responses uncorrected whose outcomes were not visible until the missile hit or
failed to hit the target, while being able to correct visible errors adequately.
This is consistent with an impairment in the central monitoring of action. Using
a similar task, we found that children with autism were more likely than controls
to fail to correct both kinds of error. Data are interpreted in terms of
difficulties with constructing visual schemata for actions.
PMID- 9656130
TI - Using objects of obsession as token reinforcers for children with autism.
AB - We assessed the effectiveness of using objects of obsession as token reinforcers
to increase task performance for children with autism. The use of obsessions as
tokens (e.g., letter "A", a picture of a train) was compared with the use of
typical tokens (e.g., stars, happy faces). A multiple baseline design across
children with a reversal within child was used. Data were collected on percentage
correct of task responses and on the occurrence of inappropriate behaviors during
work sessions. Results indicated that percentage correct on task performance was
higher when objects of obsession were used as tokens as opposed to when typical
tokens were used. Concomitant decreases in inappropriate behaviors during work
sessions were also noted. Results are discussed in terms of primary versus
secondary reinforcement and the effects of saliency and novelty of the
reinforcing stimuli.
PMID- 9656132
TI - Sex as a possible source of group inequivalence in Lovaas (1987)
AB - The possibility of differential sex proportions as a confounding factor in the
Lovaas (1987) study is raised in this paper. It is argued that the chi-square
analysis reported in the original study was inadequate and that the appropriate
comparison should be made not between the experimental group and primary control
group (Control Group 1) utilizing expected cell frequencies estimated from sample
data, but between these two groups using population data to estimate expected
cell frequencies. Implications of this interpretation are discussed.
PMID- 9656131
TI - Timing of social gaze behavior in children with a pervasive developmental
disorder.
AB - The aim of the study was to compare social initiatives and gaze behavior in low
functioning children with a pervasive developmental disorder (PDD), high
functioning children with a PDD, children with a language disorder, and normally
developing children. Behavior of the children was observed while they watched
television and performed a playful task with a parent. Compared to the high
functioning children, the low-functioning children with a PDD showed fewer social
initiatives. The high-functioning children with a PDD did not differ from the non
PDD control children in the number of social initiatives and gazes. However, in
children with PDD, timing of social gaze proved to be different in that they had
lower levels of visual checking before but not after a declarative pointing
gesture. Furthermore, they had lower levels of returning gaze.
PMID- 9656133
TI - Autism and related disorders: epidemiological findings in a Norwegian study using
ICD-10 diagnostic criteria.
AB - Recent studies of the prevalence of autism have suggested higher estimates than
previously described. Various diagnostic criteria for autism and related
disorders have been applied, with variability in case finding methodology and
characteristics of populations as well. In this study, maternal and child health
clinics covering 98% of the population were used for screening pervasive
developmental disorders. Extensive medical investigation was carried out on the
majority of cases. In this Norwegian population of children ages 3-14 years the
minimum prevalence estimate for childhood autism was 4-5 per 10,000 using ICD-10
research criteria, and did not confirm the high estimates suggested more
recently. Medical disorders identified were associated with mental retardation
rather than specifically with autism.
PMID- 9656134
TI - Risperidone for aggression and self-injurious behavior in adults with mental
retardation.
AB - Risperidone has proven efficacy with reduced likelihood of causing extrapyramidal
symptoms in the treatment of schizophrenia. Initial work suggests its utility in
the management of aggression and self injury in patients with mental retardation.
The use of risperidone in eight adult patients with moderate to profound mental
retardation is described. Risperidone in these individuals was associated with
significant reduction in aggression and self injurious behavior. Side effects
were primarily those of sedation and restlessness. These cases illustrate the
possible utility of risperidone in the treatment of aggression and self injury in
adult patients with moderate to profound mental retardation.
PMID- 9656135
TI - Diabetes insipidus and polydipsia in a patient with Asperger's disorder and an
empty sella: a case report.
AB - The paper describes a patient with Asperger disorder, Neurogenic Diabetes
Insipidus (NDI) and Primary Empty Sella (ES). His response to vasopressin
treatment suggested a concomitant presence of primary polydipsia. This is the
first reported case of an autistic spectrum disorder associated with NDI or ES.
The implications of the observed co-occurrence of these relatively rare disorders
are discussed in relation to diagnosis and pathogenesis.
PMID- 9656136
TI - Increasing speech intelligibility in children with autism.
AB - Accumulating studies are documenting specific motivational variables that, when
combined into a naturalistic teaching paradigm, reliably influence the
effectiveness of language teaching interactions for children with autism.
However, the effectiveness of this approach has not yet been assessed with
respect to improving speech intelligibility. The purpose of this study was to
systematically compare two intervention conditions, a Naturalistic approach
(which incorporated motivational variables) vs. an Analog (more traditional,
structured) approach, with developmentally similar speech sounds equated within
and across conditions for each child. Data indicate that although both methods
effectively increased correct production of the target sounds under some
conditions, functional use of the target sounds in conversation occurred only
when the naturalistic procedures were used during intervention. Results are
discussed in terms of pivotal variables that may produce improvements in speech
sounds during conversational speech.
PMID- 9656137
TI - Brief report: a case of chromosome 22 alteration associated with autistic
syndrome.
AB - The author described a male patient, age 13 years and 5 months, with behavioral
profile meeting the criteria of the autistic syndrome by the DSM-III-R (APA,
1989) and DSM-IV (APA, 1995). After clinical and laboratory examinations, it was
found that he had an abnormal karyotype, 46 XY, R(22). The need for clinical and
laboratory case studies of autism is of great importance to develop data for
defining an etiological basis for diagnosis.
PMID- 9656139
TI - Is auditory integration training safe?
PMID- 9656138
TI - Brief report: interpretation of facial expressions, postures and gestures in
children with a pervasive developmental disorder not otherwise specified.
PMID- 9656140
TI - Recently diagnosed with autism, autism or not.
PMID- 9656141
TI - Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic
shock: action mechanisms and role of CNTF receptor alpha.
AB - Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis
factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS
lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of
these activities are abolished in adrenalectomized (ADX) mice. LPS-induced
pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO)
production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone.
sCNTFR alpha did not alter the clearance or tissue distribution of CNTF.
Furthermore, CNTF variants coadministered with sCNTFR alpha protected against LPS
toxicity in a manner related to their affinity for the beta components of CNTFR.
Thus, inhibition of TNF production and protection against LPS lethality by
CNTF/sCNTFR alpha require an intact hypothalamus-pituitary-adrenal axis (HPAA)
and may be mediated by endogenous glucocorticoids. This protective effect is, at
least in part, due to the inhibition of PMN infiltration and NO production, and
appears to be mediated by cells displaying only beta-receptor subtypes.
PMID- 9656142
TI - Distinct inflammatory responses of adherent vascular lung neutrophils to
pulmonary irritants.
AB - The nature and the extent of the damage that occurs in the lung following
exposure to pulmonary irritants vary with the pathogenic agent. In the present
studies we determined if this was due to unique functional responses of adherent
vascular neutrophils to different irritants. Because of their location within the
lung, these cells may be more relevant than circulating neutrophils to the
pathophysiology of irritant-induced lung injury. For our studies we used two
model irritants, ozone and endotoxin, which cause distinct pathologic effects in
the lung. Treatment of rats with ozone resulted in a transient increase (2-fold)
in the number of adherent vascular neutrophils in the lung which was maximum 2 hr
after exposure and returned to control levels by 12 hr. In contrast, following
endotoxin administration, 10-fold greater numbers of adherent neutrophils were
recovered from the lung. Moreover, cell number remained elevated 3-fold for up to
48 hr. Unstimulated neutrophils isolated 2-12 hr after endotoxin treatment of
rats produced 3 times more superoxide anion than cells from ozone-treated rats.
Cells isolated 12-48 hr after endotoxin administration were also sensitized to
produce more nitric oxide than cells from ozone-treated rats and to express
inducible nitric oxide synthase protein. These data demonstrate that endotoxin
and ozone induce distinct patterns of accumulation and functional changes in
adherent vascular neutrophils in the lung which may contribute to different
pathological processes observed following exposure to these pulmonary irritants.
PMID- 9656143
TI - Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated
activation of the HIV-1 LTR in macrophages.
AB - The HIV-1 promoter was used as a model to identify transcription factors involved
in LPS-dependent transcription in RAW 264 murine macrophages. Expression plasmids
for Ets-2 and PU.1 trans-activated the HIV-1 LTR and recombinant PU.1 and an Ets
2 DNA binding domain/GST fusion protein bound to the 5' kappa B site of the HIV-1
enhancer. Ets-2 mRNA was LPS-inducible in RAW 264 cells and LPS stimulated
phosphorylation of threonine 72 residue within the Ets-2 pointed domain.
Induction of Ets-2 and other LPS-responsive transcription factors was also
observed upon addition of plasmid DNA, which complicates interpretation of
transient transfections. The proximal promoter region, containing two Sp1 sites,
was also LPS-responsive. We propose that the kappa B elements and the tandem Sp1
sites act as LPS response elements and that kappa B-mediated LPS action involves
Ets and rel factors.
PMID- 9656144
TI - Zero-crossing derivative spectrophotometry for the determination of haloperidol
in presence of parabens.
AB - First derivative spectrophotometry with a zero-crossing technique of measurement
is used for the quantitative determination of haloperidol in the presence of
methylparaben and propylparaben, which is added as antimicrobial preservatives in
pharmaceuticals. This technique permits the quantification of haloperidol in the
presence of parabens, with closely overlapping spectral bands, and without any
separation step. Linear calibration graphs of first derivative values (at 255.2
nm for haloperidol) versus concentration (in the range 4.0-20.0 micrograms ml-1)
were obtained with negligible intercepts. Relative standard deviation of 0.83%
was obtained for intra-day precision and 1.86% for inter-day precision. The
recovery of haloperidol in synthetic mixtures with parabens and pharmaceutical
dosage forms is also reported.
PMID- 9656145
TI - Assay of effervescent tablets by near-infrared spectroscopy in transmittance and
reflectance mode: acetylsalicylic acid in mono and combination formulations.
AB - Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid
(ASA) in three different effervescent tablet formulations. The nominal ASA
concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4%
in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with
paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was
composed of seven excipients typical of effervescent tablets. All three
formulations were measured as intact tablets in diffuse transmittance and
reflectance and as powdered tablets in diffuse reflectance. Calibration was
carried out by partial least square (PLS) regression of second derivative
spectra. High-performance liquid chromatography (HPLC) was used as the reference
method. The relative standard errors of calibration (RSEC) achieved for the three
NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for
ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in
transmittance mode were comparable with those obtained in reflectance mode, which
is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root
mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR
methods applied are thus suitable for the quantitative determination of ASA in
effervescent tablets and have the advantage over HPLC of being rapid and simply
carried out with little sample preparation; they are nondestructive and do not
require any environmentally harmful reagents.
PMID- 9656146
TI - Determination of relative acidities of some alpha, omega-bis(3-alkyl(aryl)-4,5
dihydro-1H-1,2,4-triazol-5-on-4-yl) alkanes.
AB - The solutions of nine alpha, omega-bis(3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol
5-on-4-yl) alkanes were titrated with tetrabutylammoniumhydroxide (TBAH) in
methanol, using potentiometric methods. The half neutralization potentials values
were found for all cases. Potentiometric titration curves of compounds in
methanol with 0.03 M TBAH are similar to those of weak acids obtained in aqueous
media with strong bases. Methanol is found to be a suitable medium for the weakly
acidic compounds titrated since they are poorly dissolved in other organic
solvents. A comparison among the compounds having the same alkyl chains between
the two ring systems has shown that basicity increases and acidity decreases as
the size of alkyl chains increases. However, the compound with a substituted
phenyl group was found to be the most acidic one among the examined compounds
indicating that phenyl group donates ring electrons less effectively to the
system. This can be attributed to the stability of the benzene ring.
PMID- 9656147
TI - Simultaneous determination of melatonin-pyridoxine combination in tablets by zero
crossing derivative spectrophotometry and spectrofluorimetry.
AB - Two methods have been developed for the analysis of melatonin (M) and pyridoxine
hydrochloride (PH) in combination. The first method depends on first- and second
derivative ultraviolet spectrophotometry, with the zero crossing technique of
measurement. First-derivative amplitudes at 296 nm and second-derivative
amplitudes at 294 and 322 nm are selected for the determination of M and PH,
respectively. The second method is based on the native fluorescence of both M and
PH, in methanol and 0.1 M hydrochloric acid, respectively, after a preliminary
solvent extraction procedure. The relative standard deviation of both methods was
less than 2.0%. The two methods have been successfully applied to the
determination of both drugs in laboratory-prepared mixtures and in tablets.
PMID- 9656148
TI - Separation and determination of sorbitol and xylitol in multi-component
pharmaceutical formulations by capillary isotachophoresis.
AB - Pharmaceutically important polyhydric alcohols sorbitol (SO) and xylitol (XY) are
efficiently separated and determined by analytical capillary isotachophoresis
(ITP) with conductometric detection. The on-column complex-formation equilibria
between the polyols and boric acid are utilized--the terminating borate ion acts
as the complexing agent. The ITP operational system used consists of 10 mM HCl +
20 mM imidazole (LE, pH 7.0) and 20 mM boric acid (TE, pH 8.0). The effective
mobilities of the borated SO and XY are 8.3 x 10(-9) m2 V-1 s-1 and 7.4 x 10(-9)
m2 V-1 s-1, respectively. The ITP analysis is performed with the driving and
detection currents of 50 microA (for 700 s) and 20 microA, respectively. The
calibration graphs are rectilinear in the range 25-250 mg l-1 of SO and 50 to 500
mg l-1 of XY. The method is applied to the simultaneous assay of SO and XY in
three mass-produced multi-component infusion solutions. Favourable values of the
method validation parameters obtained confirm the suitability of the proposed ITP
method for the quality control of pharmaceuticals.
PMID- 9656149
TI - GC-MS analysis of incenses for possible presence of allergenic nitromusks.
AB - A Gas chromatographic method with mass detector was developed to identify and
determine nitromusks in incense sticks of different origin (India, China, Tibet).
The proposed method was found useful to correlate dermatological allergic
reactions with the use and composition of commercial incense sticks. The incense
sticks were powdered, extracted with methanol and after the addition of 1
eicosanol as internal standard, injected into the GC-MS, using 25 m bonded phase
fused capillary column methyl, 5% phenyl silicone (0.32 mm I.D., 0.25 microns
film thickness). Musk ambrette was identified and determined in one kind of
chinese incense together with musk ketone and musk xylene. The latter compound
was also found alone in another kind of chinese incense.
PMID- 9656150
TI - Validation of a liquid chromatographic tandem mass spectrometric method for the
determination of sumatriptan in human biological fluids.
AB - A liquid chromatographic tandem mass spectrometric method for the quantitative
determination of sumatriptan base in human plasma and urine has been developed
and validated over the concentration range 0.2-20 ng base ml-1. Sumatriptan is a
5-HT1 receptor agonist which has found widespread use in the treatment of
migraine. Sumatriptan and its internal standard (D3-sumatriptan) were extracted
from human matrices using C2 solid phase cartridges. The extracts were
chromatographed on a C18 column, ionised using a heated nebuliser assisted
atmospheric pressure ionisation (API) interface and detected by MS/MS in the
multiple reaction monitoring mode. The completed validation demonstrated the
method to be robust, accurate, precise and specific for the direct quantification
of sumatriptan in human fluids. The method was used on a routine basis to
determine the levels of sumatriptan in human volunteers following the oral
administration of a 25 mg dose of sumatriptan succinate.
PMID- 9656151
TI - The control over the new obtaining procedeum of indomethacin.
AB - The synthesis of the indomethacin (1H-indole-3-acetic acid, 1(4-chlorobenzoyl)-5
methoxy-2-methyl) was achieved through a new method, which reduces some stages
from the previous methods. Both the structure of the finished product and the
structures of the intermediaries were investigated by chromatographic methods
(TLC, chromatography on column, GC-MSD) and spectroscopic methods (UV, IR, 1H
NMR, 13C-NMR). The chromatographic and spectroscopic studies proved that these
had a special analytical value and they serve to control synthesis and to
identify the compounds in all the stages of the process.
PMID- 9656152
TI - Stability of adenosine in infusion.
AB - Using liquid chromatography the stability of adenosine in aqueous solution was
investigated at five different temperatures, namely 4, 22, 37, 60 and 72 degrees
C over a period of 6 months. At the three lowest temperatures, the initial
concentration of the product was not altered, at the highest temperatures there
was a significant decrease. From these data the shelf life (t90) at room
temperature was estimated to be at least 5 years.
PMID- 9656153
TI - Reproducibility of 1H-NMR integrals: a collaborative study.
AB - The quantitative use of NMR spectroscopy was investigated by a reproducibility
study of 1H-NMR integrals involving five laboratories. A significant laboratory
effect was found confirming the difficulty to obtain very precise data by
integration of complex signals. The reproducibility of any NMR assay measurement,
which requires a high precision should be validated by an interlaboratory study.
PMID- 9656154
TI - Determination of bisnafide, a novel bis-naphthalimide anticancer agent, in human
plasma by high-performance liquid chromatography with UV detection.
AB - A simple, specific, and sensitive high-performance liquid chromatographic (HPLC)
assay utilizing ultraviolet (UV) detection for the determination of bisnafide in
human plasma was developed, validated, and applied to plasma samples from
patients undergoing cancer therapy. Plasma samples, containing an internal
standard, XE842, were first deproteinized with 2.0 ml acetonitrile, and
subsequently, 1.0 ml and pH 9 boric acid-potassium chloride-sodium hydroxide
buffer (0.1 M) was added. To this mixture, 9.0 ml of ethyl ether was added then
vortex mixed. Following centrifugation, the ether layer was back-extracted into
250 microliters of 0.1 M phosphoric acid, then removed by vacuum aspiration. A
portion of the remaining acid layer was directly injected onto the HPLC.
Bisnafide was quantified using a Shiseido Capcell Pak C8 HPLC column and
ultraviolet detection (274 nm). The lower limit of quantification was 10 ng ml-1
using 1.0 ml plasma. The intraday precision (RSD) ranged from 2.7 to 8.6% over a
concentration range of 10-1000 ng ml-1. The interday precision (RSD) ranged from
5.6 to 11.5%. Overall mean accuracy was +/- 5.2%. The drug was stable in frozen
heparinized human plasma stored at -20 degrees C for at least 1 year and stable
throughout at least two freeze-thaw cycles. This method was successfully utilized
for quantifying plasma concentrations needed to study the clinical
pharmacokinetics of bisnafide in patients undergoing cancer therapy.
PMID- 9656155
TI - Spectrophotometric and high performance liquid chromatographic determination of
cetirizine dihydrochloride in pharmaceutical tablets.
AB - Derivative spectrophotometric, colorimetric and high performance liquid
chromatographic methods, for the determination of the antihistaminic cetirizine
dihydrochloride in tablet form were described. Spectrophotometrically, cetirizine
was determined by the measurement of its first (1D) and second (2D) derivative
amplitudes at 239 (peak) and 243-233 nm (peak-to-trough), respectively. The
aqueous solutions obeyed Beer's law in the concentration ranges of 1.2-10.0 and
0.8-10.0 micrograms ml-1 for 1D and 2D measurements, respectively. The
colorimetric procedure was based on measuring the absorbency of the coloured
chromogen resulted from the reaction between cetirizine sodium salt in polar
solvent (DMF) and chloranil at 556 nm. The relation with concentrations was
linear over 120-250 micrograms ml-1. Optimization of the reaction conditions was
studied. At the same time, investigation of the complex formed was made with
respect to its composition and the associated constant. A simple liquid
chromatographic assay has been developed for the determination of cetirizine
dihydrochloride in the presence of one of its synthesis precursor (hydroxyzine
hydrochloride). A Bondapak-C18 column was used with a mobile phase consisting of
acetonitrile/0.01 M ammonium dihydrogen phosphate (32:68, v/v) containing 0.1%
w/v tetrabutyl ammonium hydrogen sulphate adjusted to pH 3 with phosphoric acid
at a flow rate of 2 ml min-1. With salicylic acid as internal standard,
quantitation was achieved with UV detection at 230 nm based on the peak height
ratios. Beer's law was obeyed in a concentration range of 3-35 micrograms ml-1
and the regression line equation was derived with a correlation coefficient of
0.9999. The validity of the methods was further confirmed using the standard
addition method. The proposed procedures were successfully applied to the
determination of cetirizine in bulk and tablet form, with high percentage of
recovery, good accuracy and precision.
PMID- 9656156
TI - An approach to the evaluation and comparison of reversed-phase high-performance
liquid chromatography stationary phases.
AB - An approach to the evaluation and comparison of reversed-phase high-performance
liquid chromatography stationary phases with particular emphasis on data analysis
and presentation is described. Assessment is based on the peak efficiency,
asymmetry (USP tailing factor) and relative retention properties shown by 24
basic compounds having a wide range of structural and physico-chemical
properties. A novel approach to data normalisation and presentation is described.
This overcomes the problems associated with the quality of the column packing
process, as well as differences in stationary phase selectivity which in
conjunction with extra column band broadening effects can make comparisons
meaningless.
PMID- 9656157
TI - Comparison of LC detection methods in the investigation of non-UV detectable
organic impurities in a drug substance.
AB - HPLC Analysis with different detection methods was shown to be essential in the
separation and identification of unknown organic impurities in a drug substance.
The impurities were found to exhibit very weak or no response to standard
ultraviolet (UV) absorption detection. LC-MS, LC-NMR, indirect, refractive index
and evaporative light-scattering detection were used to quantify and identify the
impurities in this specific case. The drug substance studied was found to be an
ideal analyte for demonstrating the advantages and limitations of several
chromatographic detection systems for impurity profile analysis.
PMID- 9656158
TI - The use of near-infrared spectroscopy in the efficient prediction of a
specification for the residual moisture content of a freeze-dried product.
AB - The purpose of this study is to improve the efficiency in the search for a
suitable specification for the residual moisture content in a freeze-dried
product. A near-infrared spectroscopic (NIRS) method was developed for the
measurement of the residual moisture content. Samples with a wide range of
residual moisture contents were stored for two months at 8, 50, and 60 degrees C.
Because of the non-destructive character of the NIRS method initially the
residual moisture content and, subsequently, the content of the active ingredient
could be measured in the same sample vials after storage. Plots of the residual
moisture content against the content of the active ingredient were made for
storage at 50 and 60 degrees C. For this only 69 samples were needed in the
stability study for the assay determination while traditionally a five-fold of
samples is needed because of the high intra-batch variability of the residual
moisture content. The plots at 50 and 60 degrees C were combined with the
Arrhenius relationship between degradation rate constant and temperature. The
maximal allowable residual moisture content was calculated with product shelf
lives of 2 and 3 years and storage temperatures of 20, 25, and 30 degrees C,
respectively.
PMID- 9656159
TI - Quantitation of amphotericin B in plasma by second-derivative spectrophotometry.
AB - A method is described for determining amphotericin B in plasma using second
derivative spectrophotometry after deproteinization. The assay was based on the
absorbance at 407.5 nm. The second-derivative spectrum recorded between 350 and
450 nm allowed identification of the analyte and showed absence of drug
interference. Only bilirubin interfered at high concentration (> or = 50 mumol l
1. The linear concentration ranges were 0.05 -5.0 mg l-1 (r = 0.999, slope =
2.731, intercept = 0.008). Between-day CV < or = 9.7%, within-day CV < or = 5.5%,
analytical recovery close to 100% were suitable for clinical investigations. This
method provides better specificity than direct absorbance, is simpler and faster
than a high performance liquid chromatography assay and can be used routinely by
any laboratory possessing a spectrophotometer with a derivative accessory.
PMID- 9656160
TI - Determination of 2-hydroxyphenylacetic acid (2HPAA) in urine after oral and
parenteral administration of coumarin by gas-liquid chromatography with flame
ionization detection.
AB - The urinary excretion of 2-hydroxyphenylacetic acid (2HPAA) was studied in human
volunteers after oral and parenteral doses of coumarin. The presence of 2HPAA in
the urine was confirmed by gas chromatography mass spectroscopy (GC MS). Mass
spectra of reference material and samples are presented. The determination of
2HPAA was carried out by GC with flame-ionization detection. Prior to analysis
samples were extracted into ethyl ether and the analytes were derivatized with
trimethlyphenylammonium hydroxide. A calibration range from 0.3 to 150 micrograms
ml-1 was established using 3-hydroxyphenyl acetic acid (3HPAA) as an internal
standard. On average less than 10% of the coumarin administered were excreted
into the urine in the form of 2HPAA.
PMID- 9656161
TI - Evaluation of a novel diffusion cell for in vitro transdermal permeation: effects
of injection height, volume and temperature.
AB - The objective of this study was to evaluate the performance of a new, compact,
dynamic diffusion cell for in vitro transdermal permeation. These so-called
Kelder-cells were developed as an automated alternative to the static Franz
diffusion cells. The new cells were used in combination with the ASPEC-system
(automatic sample preparation with extraction columns) which was initially
designed for the automation of solid-phase extractions. Three variables were
tested to optimize the performance of the new cell system: injection height into
the inlet compartment, volume flowing through the receptor compartment and
temperature. Experiments were performed using the tritium labelled
anticholinergic [3H]dexetimide permeating through an artificial membrane
(Silastic). The injection height of the needle into the inlet compartment of the
cell should be programmed at -34 mm to ensure complete air tightness, thus
forcing the buffer to flow through the cell. The volume of buffer flow through
the receptor compartment is important in maintaining sink conditions: a volume of
117 microliters was chosen to replace the total content of the cell (84
microliters) every 2 min. The temperature was precisely controlled in a
thermostatic cabinet to minimize variations in experimental conditions. For
[3H]dexetimide, an increase in temperature of 20 degrees C reduced the lag time
by a factor of approximately two, however the influence on the flux was
negligible. The data for the Kelder-cells were comparable with static Franz
diffusion cells at a pseudo-steady state, however Kelder-cells have the advantage
of automatic sampling, continuous replacement of the receptor solution, and
unattended operation over at least 24 h.
PMID- 9656162
TI - Spectrophotometric method for the determination of paracetamol and phenacetin.
AB - A rapid, sensitive and simple spectrophotometric method is proposed for the
determination of hydrolysis products of paracetamol (PRL) and phenacetin (PHN)
with sodium 1,2-naphthoquinone-4-sulphonate and cetyltrimethyl ammonium bromide
(CTA) in alkaline medium. The absorbances are measured at 570 and 500 nm and the
molar absorptivities found to be 1.118 x 10(4) and 4.54 x 10(3) l mol-1 cm-1 for
PRL and PHN, respectively. The coloured species conforms to Beer's law over the
range 1-20 micrograms ml-1 for PRL and 2-24 micrograms ml-1 of PHN. The
sensitivity is enhanced by the addition of CTA. The method is successfully
employed for determination of PRL or PHN in various pharmaceutical preparations
and laboratory made tablets and results have been statistically compared with
those obtained by the official method.
PMID- 9656163
TI - Error structure for the HPLC analysis for atenolol, metoprolol and propranolol: a
useful weighting method in parameter estimation.
AB - Three reversed-phase high performance liquid chromatography (HPLC) methods with
UV detection were developed and fully validated for the quantification of three
beta-blockers: atenolol, metoprolol and propranolol. After validation, error
structures for the HPLC analysis were established using a convenient and
practical procedure. The mean percentage of relative standard deviation (RSD) of
the experimental concentrations (C), were less than 4.29% for proportionality and
less than 3.68% for precision for any of the drugs, which allowed the
quantitation of beta-blockers assayed at concentrations in the range 25-0.78
micrograms.ml-1. The error structures for the HPLC analysis were: SD
(micrograms.ml-1) = 5.02 x 10(-2) C for atenolol, SD (micrograms.ml-1) = 4.55 x
10(-2) + 0.63 x 10(-2) C - 7.58 x 10(-6) C3 for metoprolol and SD (micrograms.ml
1) = 2.73 x 10(-2) C - 3.49 x 10(-4) C2 for propranolol. The reciprocal of the
square of the SD of the drug concentrations measured within the calibration curve
could be used as weighting methods in parameter estimation by non-linear
regression.
PMID- 9656164
TI - Determination of piroxicam and its major metabolite 5-hydroxypiroxicam in human
plasma by zero-crossing first-derivative spectrophotometry.
AB - A zero-crossing first-derivative spectrophotometric method for the determination
of piroxicam and its major metabolite 5-hydroxypiroxicam (5-HP) in human plasma
is described. This technique permits the quantification of compounds with closely
overlapping spectral bands without any separation step. The method consists of
direct extraction of the less-ionised forms of piroxicam and 5-hydroxypiroxicam
with pure diethyl ether. First derivative values at 343.5 and 332.5 nm for
piroxicam and 5-HP, respectively, were obtained. The absolute recovery of the
method was found to be 89.4% for piroxicam and 90.3% for 5-HP. Calibration graphs
are linear (r better than 0.9998), with zero-intercept, in the concentration
range 0.5-12.0 micrograms ml-1 for both compounds. The limits of quantification
attained according to the IUPAC definition were 0.29 and 0.27 micrograms ml-1 for
piroxicam and 5-HP, respectively. The results obtained by the proposed method
were in good agreement with those found by the high-performance liquid
chromatographic method (HPLC).
PMID- 9656165
TI - A rapid liquid chromatographic method for the determination of lamotrigine in
plasma.
AB - A rapid sensitive and simple high-performance liquid chromatographic (HPLC)
method for the determination of lamotrigine in plasma is described. The drug was
extracted from 100 microliters of plasma with chloroform:isopropanol (95:5% v/v)
in the presence of 100 microliters of phosphate buffer (10 mM). The extract was
evaporated and the residue was reconstituted with mobile phase and injected onto
the HPLC system. The drug and the internal standard (chloramphenicol) were eluted
from a Symmetry C18 stainless steel column at ambient temperature with a mobile
phase consisting of 0.01 M potassium-acetonitrile-methanol (70.20:10% v/v/v),
adjusted to pH 6.7, at a flow rate of 1.3 ml min-1 and the detector was monitored
at 214 nm. Quantitation was achieved by measurement of the peak-area ratio of the
drug to the internal standard and the lower limit of detection for lamotrigine in
plasma was 20 ng ml-1. The intraday precision ranged from 3.34 to 6.12%
coefficient of variation (CV) and the interday precision ranged from 2.15 to
8.34% CV. The absolute and relative recoveries of lamotrigine ranged from 86.93
to 90.71% and from 95.18 to 107.13%, respectively. The method was applied in
studying the pharmacokinetics of lamotrigine administered orally to rabbits. This
reliable micro-method would have application in pharmacokinetic studies of
lamotrigine where only small sample sizes are available, e.g. paediatric
patients.
PMID- 9656166
TI - Liquid chromatographic determination of a non-steroidal oral contraceptive CDRI
85/287 in rat serum.
AB - A precise and sensitive high performance liquid chromatographic (HPLC) assay
method was developed and validated for the quantitation of 2-[4-(2
piperidinoethoxy) phenyl]-3-phenyl-(2H)-1-benzo(b)pyran (compound CDRI-85/287) in
rat serum. This method, applicable to 0.5 ml volumes of serum, was validated
according to GLP guidelines. It involved double extraction of serum samples with
a mixture of hexane and iso-propanol (98:2 v/v) at alkaline pH and the use of UV
detection at 332 nm. Linearity, precision and accuracy were acceptable (5-200 ng
ml-1. The absolute recovery was more than 75% and the lower limit of quantitation
was 5 ng ml-1. Freeze-thaw stability studies up to four cycles showed no apparent
differences in the calculated spiked concentrations. However, in-process
stability evaluation showed the stability of the processed samples lasted up to
85 h.
PMID- 9656167
TI - Separation and estimation of seven vasodilators using packed column supercritical
fluid chromatography.
AB - This paper reports a method for an isocratic separation and simultaneous
estimation of seven vasodilators: isosorbide mononitrate (ISMN), isosorbide
dinitrate (ISDN), cyclandelate, nimodipine, amlodipine, pentifylline and
pentoxifylline using packed column supercritical fluid chromatography (SFC). An
arbitrary choice of vasodilatory compounds with respect to their chemical
structures was made to examine the viability of this technique for analysis of
drugs and pharmaceuticals. Elution was performed on a RP-C18 column. SFC offers
several degrees of freedom: temperature, pressure and modifier concentration to
attain optimum resolution and sensitivity. The effects of these parameters on
retention time have been studied using methanol modified carbon dioxide. The
analytes were identified and measured by UV-detection. The chromatographic points
of merit have been listed. Detection limits appear to be similar to those found
in liquid chromatography. Modifier concentration does generally make major
changes in retention and selectivity. A full scale validation for the seven
vasodilators has been attempted and the statistical quality evaluated.
PMID- 9656168
TI - Simultaneous detection of cisatracurium, its degradation products and propofol
using positive ion detection followed by negative ion detection in a single LC/MS
run.
PMID- 9656169
TI - Palatal augmentation prosthesis with alternative palatal vaults for speech and
swallowing: a clinical report.
PMID- 9656170
TI - A two-stage resin-bonded fixed partial denture seated in conjunction with
postextraction healing of the alveolar socket: a clinical report.
AB - A patient treatment modality that involved a two-stage resin-bonded FPD was
presented in this clinical report. During recovery of the alveolar socket, a
direct bonded acrylic pontic was seated with an adhesive resin (Super-Bond C&B
Clear). This primary prosthesis provided service for 6 months without trouble and
was effective for maintaining the open space and recovery of oral functions. The
secondarily seated resin-bonded FPD, which was made of silver-palladium-copper
gold alloy and bonded with a primer for noble alloys (V-Primer) and an adhesive
resin (Super-Bond Opaque), has been functioning satisfactorily for more than 5
years. This two-stage procedure is useful in situations that require conservative
or periodontal treatment before seating final prostheses.
PMID- 9656171
TI - Posterior resin-bonded fixed partial denture with a modified retentive design: a
clinical report.
AB - A uncomplicated clinical procedure to enhance the retention of posterior resin
bonded fixed partial dentures was described. This method involves some
modifications to the preparation and casting design and requires slightly more
time and attention at the cementation stage of the prosthetic treatment.
PMID- 9656172
TI - Temperature response in the pulpal chamber during ultrahigh-speed tooth
preparation with diamond burs of different grit.
AB - STATEMENT OF PROBLEM: Ultrahigh-speed tooth preparation can traumatize the hard
dental tissues and the dental pulp. PURPOSE: This in vitro study examined the
relationship between different grits of diamond burs on the temperature response
within a pulpal chamber during tooth preparation with a turbine. MATERIAL AND
METHODS: Newly extracted, undamaged third molars were secured by a rapid
tensioning device mounted on an air-supported slide. NiCrNi thermocouples were
inserted apically and used to determine the temperature within a pulpal chamber.
The grinding tests used cylindrical fine, coarse, and ultracoarse diamond burs.
RESULTS: The maximal temperature elevation within the pulp was 3.2 degrees C, and
the most pronounced rise in temperature occurred with ultracoarse burs.
Temperature increases in the pulpal chambers and grinding times or temperatures
of the cooling water were approximately proportional. Residual dentinal thickness
was inversely proportional to temperature elevation within the pulpal chamber.
CONCLUSIONS: This study demonstrated that coarse diamond burs resulted in more
pronounced temperature increases within the pulpal chamber during tooth
preparation. In addition, the benefit of short intervals between grinding steps
and a cooling water temperature between 30 degrees C and 32 degrees C was
confirmed. A cooling temperature of 38 degrees C to 43 degrees C did not afford
actual cooling.
PMID- 9656173
TI - Effect of enamel and dentin surface wetness on shear bond strength of composites.
AB - PURPOSE: This study investigated the effect of the wetness of human enamel and
dentin surfaces on the shear bond strength of composites. MATERIAL AND METHODS:
Seven dentin bonding systems were used. Three methods of preparing the enamel or
dentin surface before applying primer or bonding agent were adopted as test
conditions: wet (blot dried), semidry (3-second air blast), and dry (15-second
air drying). Shear bond strength was measured with a universal testing machine.
Mean bond strengths were analyzed with analysis of variance and Scheffe's F-test.
Enamel and dentin surfaces were observed by a dissecting microscope after shear
bond testing. RESULTS: Enamel specimens tested by all systems and dentin tested
by two systems did not reveal significant differences in shear bond strengths (p
> 0.05). Among dentin specimens tested by two systems with water-based primers,
the shear bond strength values of the dry technique group were higher than those
of the other two groups (p < 0.05). However, among dentin specimens tested by
systems having acetone-based primers or bonding agents, bond strength values of
the wet or semidry technique groups were higher than those of the dry technique
group (p < 0.05). CONCLUSION: It was concluded that some water might be needed by
dentin surfaces or for primers to obtain high bond strength on the dentin
surface, but that drying methods did not affect bonding strength to enamel
surfaces either before priming or after conditioning.
PMID- 9656174
TI - The effect of tin-electroplating on the bond of four dental alloys to resin
cement: an in vitro study.
AB - STATEMENT OF THE PROBLEM: Nickel-chromium alloys are indicated for the
construction of resin-bonded fixed partial dentures; however, the potential
toxicity of nickel has been a source of concern. Composite cements do not develop
an adequate bond to air abraded noble alloys, which cannot be electrolytically
etched. Tin-electroplating of noble alloys appears to be an alternative treatment
for resin bonding. PURPOSE: This in vitro study investigated the effect of tin
electroplating on the bond of a composite cement to base and noble alloys.
MATERIAL AND METHODS: Tensile tests were made with disks of four alloys that were
cemented to each other with an adhesive composite cement after (1) air abrasion
with 50 microns aluminum oxide and (2) air abrasion plus tin-electroplating.
RESULTS: Tin-electroplating increased the bond strength of metal-ceramic gold
alloy (Au,Pd,Pt) to a level comparable to the nickel-chromium alloy, but had a
harmful effect on type IV gold alloy. CONCLUSIONS: Despite the recommendation for
tin-electroplating of type IV gold alloys, this procedure did not improve bond
strength to composite in this study.
PMID- 9656175
TI - In vitro study of the number of surface defects in monophase and two-phase
addition silicone impressions.
AB - STATEMENT OF PROBLEM: Monophase addition-cured silicone impression materials in
stock trays are considered to be alternatives to two-phase systems used with
custom trays. PURPOSE: This study compared the number of surface defects in
addition-cured silicone impressions recorded with monophase materials in stock
trays and two-phase impressions in custom trays. METHODS: The number of voids
visible on the surface of impressions recorded in vitro were counted. Two
monophase impression materials. (President Monobody system 75, Bayer Cutter) in
stock trays were compared with impressions recorded with two-phase addition
silicone materials (President Plus light-body/regular-body and Zhermack Elite
light-body/medium-body) in custom trays. A total of 200 automixed impressions, 50
with each material, were recorded of 50 dentoform molar teeth prepared for full
veneer crowns. Impressions were examined for surface voids anywhere on the
prepared part of the tooth by a trained examiner. RESULTS: Mean number of voids
observed for the monophase impressions were 3.0 +/- 2.2 for President Monobody
system and 3.4 +/- 2.0 for Bayer Cutter system. Mean number of voids for the two
phase materials were 0.8 +/- 1.0 for President Plus, and 1.0 +/- 1.1 for Zhermack
Elite. No significant differences were observed for number of voids between the
monophase materials or between the two-phase systems (ANOVA and Neuman-Keuls p >
0.05). However, both two-phase materials in custom trays had significantly fewer
surface voids than the two-monophase materials (ANOVA and Neuman-Keuls, p <
0.001) used in stock trays. CONCLUSION: Monophase addition-cured impression
materials in stock trays carries an increased risk of void formation on the
surface of the impression when compared with two-phase addition silicone
materials in custom trays.
PMID- 9656176
TI - Treatment outcomes with mandibular removable partial dentures: a population-based
study of patient satisfaction.
AB - STATEMENT OF PROBLEM: Little is known about the outcomes of treatment with
mandibular removable partial dentures provided by dentists in private dental
practice. PURPOSE: This study examined 15 aspects of patient satisfaction and
explored the factors found to be associated with dissatisfaction. MATERIAL AND
METHODS: A questionnaire was mailed to people whose dental insurance claims
included CPT Code 5214 within the last 5 years. A composite measure of treatment
outcome was created by combining the responses to the 15 satisfaction items, and
10 factors were then tested statistically to determine their relationship to
dissatisfaction. RESULTS: A majority of the respondents were satisfied with the
prosthesis, but a substantial amount of dissatisfaction existed. Dissatisfaction
was greater when there was no previous wearing experience or when there was an
opposing maxillary removable partial denture. Respondents under the age of 60
expressed more dissatisfaction than did those over the age of 60, and subjects
with lower levels of general health also reported less satisfaction. One third of
the respondents believed their prosthesis required adjustment or replacement, and
one fourth said the removable partial denture had caused a problem with the
natural teeth. CONCLUSION: A majority of survey respondents treated with a
mandibular removable partial denture in private dental practice were satisfied
with the prosthesis, but a substantial amount of dissatisfaction existed.
Dissatisfaction was related to age, health, prior experience with a prosthesis,
and the type of opposing dentition.
PMID- 9656177
TI - Evaluation of resilient abutment components on measured strain using dynamic
loading conditions.
AB - STATEMENT OF PROBLEM: Factors that affect transmission of strain from prostheses
to bone may affect the long-term success of loaded implants. Current in vitro
models are theoretically predictive (finite element modeling) or facsimile
(photoelastic) in nature. A more clinically relevant in vitro model for strain
evaluation should be investigated. PURPOSE: This study attempted: (1) to validate
a human cadaver bone model for vitro measurement of cortical bone strain, and (2)
to evaluate the effect on cortical strain measurements of a resilient plastic
component incorporated within a titanium implant in response to variable dynamic
loading. MATERIAL AND METHODS: Two IMZ (Interpore International) abutment
alternatives were used: the titanium Abutment Complete and the polyoxymethylene
Intra-mobile Element. The model system consisted of two implants placed in
unfixed human cadaver ulna bone to simulate an implant bound edentulous region.
Four biaxial rosette strain gauges simultaneously recorded cortical bone strain
immediately mesial and distal to each implant. During experimentation a simulated
prosthetic framework supported by either titanium or polyoxymethylene abutments
was dynamically loaded 6 min from the terminal abutment along a cantilever
extension. Cyclic nominal peak loads were applied with a materials testing
machine at 20-N intervals from 20 to 200 N at a crosshead speed of 5 mm/minute.
The protocol allowed frequency of load application to vary. A Newtonian linear
correlation (r2 > or = 0.98) between load application and strain output was
determined for each gauge position except for the terminal gauge located opposite
the cantilever. RESULTS: Cortical strains recorded were within reported
physiologic ranges involved in bone modeling and remodeling. Further, the
polyoxymethylene abutment components did not result in reduction of peak
microstrain at any gauge position. The Intra-mobile Element abutments, however,
did increase the time required to complete 10 loading cycles when compared with
the titanium Abutment Complete abutments for the crosshead speed and ultimate
loads evaluated. CONCLUSIONS: Results indicate the cadaver bone behaved in an
elastic manner within the load range evaluated, and as such represents a viable
in vitro experimental model. Under these conditions, polyoxymethylene abutment
components do not affect measurable bone strain in response to variable loading
when compared with titanium.
PMID- 9656178
TI - A method for quantifying complete denture quality.
AB - STATEMENT OF PROBLEM: Reproducible and quantitative clinical evaluation of
complete denture prostheses is of great importance for preoperative diagnosis,
treatment planning, and assessment of quality of denture treatment. PURPOSE: This
study attempted (1) to clarify the degree of contribution each clinical factor
made to the general assessment of experienced prosthodontists to complete denture
prostheses, and (2) to develop a method for quantitative assessment of complete
denture quality. METHODS: Sixteen clinical factors with a three-grade scale were
used to evaluate complete denture prostheses in 320 patients. The general
assessment of the dentures was conducted with a 10-point scale. The contribution
of each grade of the 16 factors to the general assessment level was determined by
a multiple regression analysis. RESULTS: Seven factors were highly correlated to
the general assessment. On the basis of these significant contributions, a
complete denture scoring method was established followed by the calculation of
the category scores of these factors and conversion of the total sum of each
category score to an integer number between 0 and 100. The resultant
quantification score was closely correlated with the general assessment of the
denture. CONCLUSION: An evaluation protocol used for scoring of complete dentures
was developed based on the scientifically analyzed knowledge of experienced
prosthodontists.
PMID- 9656179
TI - Alternate framework designs for removable partial dentures.
AB - STATEMENT OF PROBLEM: The removable partial denture is usually less appreciated
than the fixed partial denture by both patients and prosthodontists. This
negative attitude could be due to problems associated with the wearing of a
removable partial denture and concern essentially with comfort, esthetics,
masticatory function, occlusal stability, and maintenance of oral hygiene. Such
problems could be limited if treatment planning is made carefully, according to
simplified and logical principles for framework design, and if oral hygiene and
the fit of the dentures are regularly controlled. PURPOSE: This article reviews
the factors associated with the prognosis of treatment with removable partial
dentures. Furthermore, the article describes framework design applied in
different clinical situations and compares them with more conventional designs.
It seems important to consider a framework design that privileges comfort,
esthetics, and oral hygiene rather than to follow mechanical rules that are
entirely theoretical and have not been confirmed scientifically or clinically.
PMID- 9656180
TI - Pattern of occlusal contacts in lateral positions: canine protection and group
function validity in classifying guidance patterns.
AB - STATEMENT OF PROBLEM: The concept of canine protection and group function lack
consistency in the definitions and examining methods, and a valid system for
evaluating and classifying occlusal contact patterns has not been established.
PURPOSE: This study assessed the use of canine protection and group function in
classifying occlusal guidance in the natural dentition. MATERIAL AND METHODS:
Occlusal contacts of 86 young adults were examined with shim stock in regulated
lateral positions, 0.5,1,2 and 3 mm from the maximum intercuspation. The patterns
of occlusal contacts varying with the lateral position were described. RESULTS:
Focusing on the working-side contact only, most contact patterns belonged to
group function, and a few to canine protection. Focusing on both the working and
nonworking side contacts, nearly half the contact patterns were those other than
canine protection and group function and were classified into balanced occlusion.
CONCLUSION: The validity of the classification system using canine protection and
group function is questionable. A new classification system of occlusal guidance
is desirable.
PMID- 9656181
TI - The effect of pretreatment with an oxalic acid solution on marginal adaptation to
enamel in vivo.
AB - STATEMENT OF PROBLEM: New acids such as oxalic acid have been introduced as a
conditioning agent in the total-etch technique. There is concern about long-term
retention of the acid on enamel in relation to the superficial etch effect.
PURPOSE: This in vivo study evaluated the marginal adaptation to enamel
conditioned with either and oxalic acid solution or a phosphoric acid with SEM
replica technique. MATERIAL AND METHODS: Twenty-four patients received one of
each of three class III restorations. Two cavity preparations were pretreated
with aluminum nitrate/oxalic acid/glycine solution 1 of the Gluma 2000 system.
The first cavity was primed and sealed with Gluma 2000 solution 2, the second
cavity with Gluma 3 and 4. The third cavity was conditioned with phosphoric acid
(Gluma 1) and sealed with the bonding resin Gluma 4. All three cavities were
restored with a hybrid resin composite (Pekafill). At baseline and after 1 year,
replica impressions were made to study the margins with SEM. Semiquantitative
analysis of the enamel interfaces was performed (x200 and x1000 magnifications).
Marginal quality of the three restorative systems were compared and tested
intraindividually. RESULTS: The three restorations exhibited good enamel marginal
adaptation and a high percentage of gap-free margins at baseline, 96% to 97% of
the total length of margins investigated. Marginal quality decreased
significantly after 1 year for all three groups. Gap-free margins were observed
in 81% to 85% of the marginal length. No significant differences were found among
the groups. CONCLUSION: Despite a less pronounced etch pattern created by
conditioning of enamel with the oxalic acid solution, a good enamel marginal
quality was observed at both evaluation times, comparable to the marginal
adaptation of the phosphoric acid conditioned cavities.
PMID- 9656182
TI - Annual review of selected dental literature: report of the Committee on
Scientific Investigation of the American Academy of Restorative Dentistry.
PMID- 9656183
TI - Tooth position index for the fabrication of a mandibular implant-supported
overdenture bar.
AB - This article describes an index for the fabrication of a mandibular implant
supported overdenture bar. The index is a two-piece mold made from an addition
silicone putty material. It is used to record and maintain the relative position
of the morphologic contours of the trial denture to the master cast. The split
mold design permits direct visualization of the amount of space available for the
design of the retentive bar from both the facial and lingual aspects while
ensuring room for an adequate thickness of the denture base resin, without the
need to remove the teeth from the trial denture wax-up.
PMID- 9656184
TI - The new removable denture patient: treatment procedures.
AB - Dentists are beginning to see a new type of patient who requires removable
prosthodontic rehabilitation. These patients are the result of both increases in
longevity and dental treatment that has retained teeth, despite the onslaught of
caries and periodontal disease. The current procedures for transitioning patients
into removable prostheses can be modified for this new group of patients. This
article presents a transition procedure for patients who are receiving removable
prostheses, which dissociates the surgical phase of treatment from the prosthetic
stage. The patient's existing teeth are incorporated into a removable prosthesis
in a way that ensures the exact replication of the tooth position in the oral
cavity. This method addresses many of the inadequacies of current procedures
while at the same time requiring a minimum of chair time. Even with this
procedure, this transition is still difficult for the patient.
PMID- 9656185
TI - 1997 Judson C. Hickey Scientific Writing Awards. An innovative investment method
for the fabrication of a closed hollow obturator prosthesis.
AB - An investment method is described for fabrication of a closed hollow obturator
based on the use of three sections of a denture processing flask. The thickness
of the obturator portion is minimized and all surfaces exposed to the oral cavity
are processed with heat-polymerized acrylic resin. The technique eliminates
additional steps noted in the literature, allowing for the prosthesis to be
processed to completion from the wax trial denture. This technique provides a
lightweight and seamless obturator and can be used for complete or partially
edentulous cases. Clinical and laboratory time are minimized while fabricating a
durable, virtually water-tight prosthesis that can be used alone or in
conjunction with an extraoral prosthesis.
PMID- 9656186
TI - A new approach to fabricating the occlusal surfaces of removable prostheses.
AB - A procedure is introduced to fabricate the occlusal surfaces of removable
prostheses that oppose ceramic restorations or ceramic denture teeth. It involves
the use of a heat-processed glass ceramic material in the form of onlays over the
plastic denture teeth. This procedure provides for more wear compatibility,
improved esthetics, and individualized occlusion.
PMID- 9656187
TI - Cell transformation assay: a surrogate for cancer risk?
PMID- 9656188
TI - Gut transfer and doses from environmental plutonium and americium.
PMID- 9656189
TI - Transformation of C3H 10T1/2 cells by low doses of ionising radiation: a
collaborative study by six European laboratories strongly supporting a linear
dose-response relationship.
AB - For the assessment of radiation risk at low doses, it is presumed that the shape
of the low-dose-response curve in humans for cancer induction is linear.
Epidemiological data alone are unlikely to ever have the statistical power needed
to confirm this assumption. Another approach is to use oncogenic transformation
in vitro as a surrogate for carcinogenesis in vivo. In mid-1990, six European
laboratories initiated such an approach using C3H 10T1/2 mouse cells. Rigid
standardisation procedures were established followed by collaborative
measurements of transformation down to absorbed doses of 0.25 Gy of x-radiation
resulting in a total of 759 transformed foci. The results clearly support a
linear dose-response relationship for cell transformation in vitro with no
evidence for a threshold dose or for an enhanced, supralinear response at doses
approximately 200-300 mGy. For radiological protection this represents a large
dose, and the limitations of this approach are apparent. Only by understanding
the fundamental mechanisms involved in radiation carcinogenesis will further
knowledge concerning the effects of low doses become available. These results
will, however, help validate new biologically based models of radiation cancer
risk thus providing increased confidence in the estimation of cancer risk at low
doses.
PMID- 9656190
TI - Transfer across the human gut of environmental plutonium, americium, cobalt,
caesium and technetium: studies with cockles (Cerastoderma edule) from the Irish
Sea.
AB - Our previous studies have indicated lower values of the gut transfer factor ('f1
values') for plutonium and americium in winkles (Littorina littorea) than adopted
by ICRP. The present study was undertaken primarily to investigate whether this
observation extends to other species. Samples of cockles (Carastoderma edule)
from Ravenglass, Cumbria were eaten by volunteers who provided 24 h samples of
urine and faeces. Urine samples indicated f1 values for cockles which were higher
than for winkles; for plutonium these ranged overall up to 7 x 10(-4) with an
arithmetic mean in the range (2-3) x 10(-4), and for americium up to 2.6 x 10(-4)
with an arithmetic mean of 1.2 x 10(-4). Limited data based on volunteers eating
cockles from the Solway suggest that f1 values for americium may be greater at
distance from Sellafield. The measured values compare with 5 x 10(-4) used by the
ICRP for environmental forms of both elements, which would appear to provide
adequate protection when calculating doses from Cumbrian cockles. Data for other
nuclides were obtained by analysing faecal samples from the volunteers who ate
the Ravenglass cockles. Cobalt-60 showed an f1 value in the region of 0.2, twice
the value currently used by ICRP. For 137Cs, variabilities were indicated in the
range 0.08 to 0.43, within the ICRP value of f1 = 1.0. Technetium-99 gave f1
values up to about 0.6, in reasonable conformity with the ICRP value of 0.5.
PMID- 9656191
TI - Discharges of krypton from Sellafield, 1951-1997, and the resultant doses to
members of the public.
AB - The radionulide 85Kr, which has a half-life of 10.72 years, is produced, almost
exclusively, by reprocessing operations during which the fission product is
released from irradiated nuclear fuel by chemical dissolution. Reprocessing
plants at Sellafield, in Cumbria, have released the noble gas to atmosphere since
operations commenced in 1952. Historically, krypton discharges were classified
for security reasons, although these have been monitored and published by BNFL
for each year since 1977. This paper reviews discharges of 85Kr from Sellafield,
and consequent radiation doses, since its earliest operations. Over the past
three years, discharges of 85Kr have increased due to the operation of the
Thermal Oxide Fuel Reprocessing Plant (Thorp). Nonetheless, the associated annual
committed effective dose to individuals remains low, peaking around 1.5 microSv a
1 to the identified critical groups, which compares with typical annual committed
effective doses from natural sources of radiation of 2200 microSv. Maximum
collective doses predicted from any single year of operations are 0.6 man Sv, 2
man Sv and 42 man Sv to the UK, Europe and the world respectively. Comparison may
be made to natural background committed effective doses, which are of the order
of 130,000 man Sva-1, 750,000 man Sva-1 and 13,000,000 man Sva-1 to the UK, EU
and world populations respectively.
PMID- 9656192
TI - A review of the cost effectiveness of radon mitigation in domestic properties in
Northamptonshire.
AB - The costs of remedial work, and the radon level reduction achieved, have been
studied in a series of domestic properties in Northamptonshire, which is a radon
affected area. The cost-effectiveness of the series is similar to published
theoretical estimates for proposed national remediation programmes, and five
times more effective than our similar analysis for the National Health Service
workplace, if it is assumed that 100% of householders discovering levels above
300 Bq m-3 implement remediation. In practice, in the UK, far fewer of those who
arrange an initial radon test proceed to remediation, but this domestic programme
could be cost effective if more than 5% carry out remediation. Our series
confirms that a considerable number of householders with radon levels in the 200
to 300 Bq m-3 range do not seek or implement remediation work.
PMID- 9656193
TI - Development of revised Ionising Radiations Regulations.
AB - New standards in ICRP60 led to the revision of the 1980 European Basic Safety
Standards Directive, which in turn has created the necessity to revise the
Ionising Radiations Regulations 1985. Proposals from the Health and Safety
Commission (HSC) for revised regulations are currently out for public
consultation in a formal Consultative Document. This article describes some of
the background to the proposals in the Consultative Document, key influences on
the revision process and the methods used to develop the proposal so that they
are broadly acceptable to stakeholders. Some of the changes proposed are
structural in nature, such as integration of the provision of the Outside Workers
Regulations. Others are of a legal nature and include: new proposals for
justification, prior authorisation and risk assessment; two options for the dose
limitation system; and significant changes to the means of recognising the
competence of the Radiation Protection Adviser. Following the current public
consultation, final proposals need to be drawn up, approved by HSC and cleared
through the European Commission under procedures required by the Euratom Treaty.
If all goes according to plan, the revised regulations should be on the Statute
Book about the middle of next year, with most provisions coming into force on 1
January 2000.
PMID- 9656194
TI - The European Directive on health protection of individuals against the dangers of
ionising radiation in relation to medical exposures (97/43/EURATOM).
AB - On 30 June 1997 the Council of Ministers approved the Directive on the Health
Protection of Individuals in relation to Medical Exposures (MED) (97/43/EURATOM).
This MED must be implemented in national law no later than 13 May 2000, repealing
at that time Directive 84/466/EURATOM, the so-called 'Patient Directive'. It
complements the Basic Safety Standards Directive of 1996 (96/29/EURATOM) as
regards medical exposures, which comes into force at the same date. The MED
considerably extends the scope of application from exposures of patients to all
exposures directly or indirectly related to medical uses of ionising radiation.
The MED reaffirms the objectives of the 1984 Directive--to aim at optimum
diagnostic efficacy at reasonable dose to the patient and to reduce the number of
unnecessary and inadequate exposures--but also strengthens most of its
requirements as a result of the experience gained with its implementation and, at
the same time, adds new provisions considered important taking into account
scientific and technical evolution in the radiological field. In particular those
exposures where there is no direct health benefit for the person undergoing the
exposure and exposures at great risk are given special attention. With the aim of
facilitating the implementation of the MED in national legislation the European
Commission, with the help of the group of experts established under article 31 of
the EURATOM Treaty, will produce technical guidelines with further explanation on
some of the requirements of the MED.
PMID- 9656195
TI - Lasers in places of public entertainment.
PMID- 9656196
TI - [Comparison of chemotherapy CHOP vs. CHOP/VIA in the treatment of aggressive non
Hodgkin's lymphoma: a randomized multicenter study of 132 patients. The PETHEMA
group. Program for Study and Therapeutics of malignant hemopathies. Spanish
Association of Hematology and Hemotherapy].
AB - BACKGROUND: To compare standard chemotherapy CHOP (cyclophosphamide, adriamycin,
vincristine and prednisone) with the regimen CHOP/VIA (VP-16, iphosphamide and
cytarabine) in terms of response to therapy, response duration, survival and
toxicity in patients with aggressive lymphoma. PATIENTS AND METHODS: 132 patients
(84 males and 48 females; median age, 55 years) were included from 12 Spanish
Institutions, diagnosed of non-Hodgkin's lymphoma of intermediate or high grade,
in stages II-IV and previously untreated. Patients were randomized to receive
CHOP or CHOP/VIA. RESULTS: After excluding 14 not assessable cases, 62 patients
(52.5%) received CHOP, and 56 (47.5%) CHOP/VIA. No significant differences were
found on main prognostic factors between such groups. Response was assessable in
114 cases (CHOP: 61; CHOP/VIA: 53) 39 patients (64%) receiving CHOP achieved
complete response (CR), and 2 (3%) partial response (PR), whereas in the CHOP/VIA
group CR and PR rates were 63% (34/53), and 7% (4/53), respectively. 14 patients
(36%) treated with CHOP and 12 (35%) treated with CHOP/VIA eventually relapsed,
with an actuarial risk of relapse at 36 months of 43% and 40%, respectively.
Median survival was 37 months. No differences were found between both therapeutic
groups, with an overall survival at 36 months from diagnosis of 53.5% (CI 95%: 40
67) for CHOP and 48% (CI 95%: 34-62) for CHOP/VIA. Finally, toxicity was not
different for both arms. CONCLUSION: In the present study in patients with
aggressive NHL chemotherapy regimens CHOP and CHOP/VIA showed similar results in
terms of response, response duration, survival and toxicity.
PMID- 9656197
TI - [Plasma homocysteine levels in patients with ischemic cerebral infarction].
AB - BACKGROUND: Moderate hyperhomocysteinemia is an independent risk factor for
stroke. The relationship between homocysteinemia and stroke and its related
factors are unknown in Spain. PATIENTS AND METHODS: We determined plasma
homocysteine concentrations in 80 stroke patients and in 48 control subjects
without vascular risk factors. Folate, vitamin B12 and creatinine concentrations
were also measured in stroke patients. RESULTS: Total plasma homocysteine
concentrations were higher in stroke patients compared to controls (11.2 [SD 3.2]
mumol/l versus 8.1 [2.6] mumol/l; p < 0.001). Hyperhomocysteinemia was present in
20% of patients and in 2.2% of controls (odds ratio [OR] = 5.75; 95% CI = 1.24
53.4; p < 0.01). Homocysteine values were related to vitamin B12 (r = 0.28; p <
0.05) and creatinine concentrations (r = 0.24; p < 0.05). Multiple regression
analysis showed that about 15% of the variation in plasma homocysteine
concentrations could be predicted by the values of vitamin B12 (p < 0.001) and
creatinine (p < 0.05). Homocysteine values were unrelated to age, sex, folate
concentrations, atherosclerotic subtype or to the presence of vascular risk
factors. CONCLUSIONS: Moderate hyperhomocysteinemia was present in about 20% of
stroke patients in our series. Homocysteine plasma level was not related with
other stroke risk factors or with the atherosclerotic subtype of stroke, but it
was partially related with the renal function parameters and the serum levels of
vitamin B12.
PMID- 9656198
TI - [Availability, use and cost of antidotes in Catalonia].
AB - BACKGROUND: To know the availability of antidotes in hospital and extra-hospital
emergency services in Catalonia (Spain), their real use, and the cost. PATIENTS
AND METHODS: Availability was studied by means of a transversal questionnaire
carried out in 24 hospitals and 3 extra-hospital emergency services in Catalonia;
the real use of antidotes was investigated using a prospective study carried out
for one year in the same 24 hospitals, and the cost was determined using the data
obtained over 12 months in one large hospital. RESULTS: Average availability was
35 antidotes in hospital and 13 in extra-hospital emergency services. In no
service did the availability coincide exactly with that of another service, nor
with the recommendations made by international institutions (World Health
Organization and International Programme for Chemical Safety) or the Government
of Catalonia. The low incidence of availability of antidotes to cyanide was
notable. Antidotes were used in 12.9% of acute intoxications. In 167 cases
treated with these drugs, only 9 different antidotes were used. The consumption
of these antidotes represents 0.1% of the budget of a pharmacy service in one
large hospital. CONCLUSIONS: The availability of antidotes in Catalonia is
heterogeneous and some services lack antidotes whose use is considered essential.
Antidotes are scarcely used in acute intoxications and their economic cost is
low.
PMID- 9656199
TI - [Treatment of aggressive non-Hodgkin's lymphomas].
PMID- 9656200
TI - [Chaos and medical prediction].
PMID- 9656201
TI - [Molecular cardiology: toward gene therapy].
PMID- 9656202
TI - [A 37-year-old woman with deafness, decrease of visual acuity, dysarthria,
myoclonus and changes in eye movements of a 20-year evolution
(clinicopathological conference)].
PMID- 9656203
TI - [Optic neuritis and the risk of development of multiple sclerosis].
PMID- 9656204
TI - [Hepatic toxicity and amlodipine].
PMID- 9656205
TI - [The miracle of melatonin in Spain].
PMID- 9656206
TI - [Teaching of clinical nutrition in Spain].
PMID- 9656207
TI - [Effects of dietary fat saturation on levels of plasma lipoprotein (a) and
lipids].
AB - BACKGROUND: Lipoprotein (a) (Lp[a]) is a known risk factor for coronary heart
disease. Lp(a) plasma concentration mainly depends on genetic polymorphism. The
aim of this study was evaluate the effect of dietary fat saturation on Lp(a)
plasma concentration. SUBJECTS AND METHODS: Forty two subjects (eighteen women
and twenty four men) were placed in four consecutive 5 weeks diet periods. Energy
intake from proteins, carbohydrates and fats was constant during the study and
there were only changes on fatty acids composition. First period was enriched in
saturated fatty acids (SFA), second period in monounsaturated fatty acids (MUFA)
and third and fourth periods were enriched in polyunsaturated fatty acids (PUFA).
Fourth period was also enriched in PUFA n-3 (blue fish). RESULTS: Changes on
dietary fat saturation had a significant effect on plasma lipids and
lipoproteins. Lp(a) plasma concentration was minimum in SFA phase (6.8 [SD 7.3]
mg/dl), increasing during MUFA phase (8.7 [8.5] mg/dl) and was maximum in PUFA n
6 and PUFA n-3 (11.5 [11.1] and 12.7 [11.9] mg/dl, respectively) (p < 0.0001).
CONCLUSIONS: Changes on dietary fat saturation significantly modify Lp(a) plasma
concentration. These variations went in opposite direction to LDL-cholesterol
modifications and were clinically irrelevant.
PMID- 9656208
TI - [Genetic polymorphism of vitamin D receptor and osteoporosis].
AB - BACKGROUND: Genetic factors condition an important part of bone mass. The role of
vitamin D receptor polymorphism (VDR) as genetic marker of osteoporosis is a
matter of discussion. We have studied the possible influence of VDR on bone
remodelling, calciotropic hormones, on the presence of osteoporosis and
osteoporotic bone fractures. PATIENTS, CONTROL POPULATION AND METHODS: A case
control study. We have studied a total of 127 postmenopausal Canarian women from
Canary Islands, Spain; 66 healthy controls and 61 with the diagnosis of
osteoporosis, which was made by clinical, radiological and densitometric
criteria. 17 osteoporotic women have had a fracture: Colles, hip or vertebral
(spinal deformity index) fracture. VDR were determined by PCR directed to
demonstrate the presence (b) or absence (B) of a restriction target for Bsml in
intron 7. We analyzed some biochemical markers of bone remodelling: serum levels
of alkaline phosphatase, tartrate resistant acid phosphatase and urine ratios of
calcium/creatinine and hydroxyproline/creatinine. We also determined calciotropic
hormones: parathyroid hormone and calcitonin. Bone mass was measured by DEXA and
TC. RESULTS: There were no significant differences in either biochemical bone
remodelling markers or in bone mass between the three genotypes: bb, Bb and BB,
either in controls or in osteoporotic women with the exception of alkaline
phosphatase which had a significative increase compared to control in women with
unfavorable alleles distribution (bB and BB). Distribution of genotypes was
similar between controls and osteoporotic women, with or without fractures.
CONCLUSIONS: In Canarian women, VDR genotype is not associated with changes in
biochemical markers of bone remodelling or in bone mass or with the presence of
osteoporosis or osteoporotic fractures.
PMID- 9656209
TI - [Epidemiological study on the incidence of inflammatory bowel disease in 4
Spanish areas. Spanish Group on the Epidemiological Study of Inflammatory Bowel
Disease].
AB - BACKGROUND: The incidence of inflammatory bowel disease (IBD) shows marked
geographical variations. The aim of this study was to determine and compare the
incidence of IBD in four Spanish areas: Sabadell (Northeast), Vigo (Northwest),
Mallorca island and Motril (South). PATIENTS AND METHODS: Prospective survey
based on inception cohorts over a two-years period (1 October 1991 to September
1993). Subjects were the patients resident in these areas and diagnosed of IBD
according to a standard protocol for case ascertainment and definition. RESULTS:
Altogether 328 cases were identified, of whom 191 were diagnosed as ulcerative
colitis (UC), 135 as Crohn's disease (CD) and 2 as indeterminate colitis. The
overall adjusted incidence rate per 100,000 persons between ages 15-64 years of
UC and CD were respectively 9.8 and 5.2 in Sabadell, 7.7 and 5.0 in Vigo, 7.8 and
5.8 in Mallorca and 4.3 and 6.5 in Motril. The Incidence rate ratio showed no
significant differences for either conditions among these areas. The global
adjusted incidence rate of UC in Spanish areas (8.0; IC 95%: 6.3-9.7) was
significantly lower to that of Northern European countries while that of CD (5.5;
IC 95%: 4.1-6.9) was between that of Northern and Southern Europe with no
significant differences. CONCLUSIONS: The incidence of IBD did not show
differences among the Spanish areas, and rates are between 2 and 6 times higher
than those previously reported. The incidence of UC is significantly lower than
that observed in the North of Europe, while for CD the incidence is between that
of Northern and Southern Europe.
PMID- 9656210
TI - [How many HIV's are there?].
PMID- 9656211
TI - [Detection of human herpesvirus 8 in patients with Kaposi's sarcoma or
Castleman's disease associated with AIDS].
AB - A new herpesvirus provisionally termed as KSHV or HHV-8 has been detected in
lesions from AIDS-based Kaposi's sarcoma (KS) and from other KS clinical forms,
and also in other tumors such as body cavity-based lymphomas or Castleman's
disease (CD). We have assessed the presence of this novel herpesvirus in
specimens from patients diagnosed with either AIDS and KS or AIDS and CD. DNA
samples from skin lesions and peripheral blood obtained from 8 patients diagnosed
with AIDS, seven with KS and one with multicentric CD were analyzed; skin
specimens and peripheral blood samples from volunteer blood donors or from KS and
CD free HIV seronegative patients were used as controls. Detection of the virus
was done by PCR amplification of KS330 region, one of the HHV-8 sequences first
reported. All skin lesions analysed tested positive for KS330; peripheral blood
samples from 5 of the patients, including the one diagnosed with CD, showed also
the virus sequence. All skin specimens and peripheral blood samples from controls
were negative. From our results it can be concluded that the novel herpesvirus
HHV-8 can also be detected in patients with AIDS-associated KS and AIDS
associated CD in Spain.
PMID- 9656212
TI - [The truth and its disclosure to the patient].
PMID- 9656213
TI - [The antioxidant capacity of melatonin: its defensive role against age-related
diseases].
PMID- 9656214
TI - [Markers of hepatitis A and B virus infection in workers of a municipal sanitary
enterprise].
PMID- 9656215
TI - [Why do research?].
PMID- 9656216
TI - [Methicillin-resistant Staphylococcus aureus infection in a geriatric unit for
acutely ill].
PMID- 9656217
TI - [Behcet's disease and relapsing polychondritis (MAGIC syndrome) associated with
antiphospholipid syndrome].
PMID- 9656218
TI - [Sudden decrease of HIV/AIDS mortality in the community of Madrid].
PMID- 9656219
TI - [Genotypes of hepatitis C virus: their relationship with risk factors, the
severity of liver disease, and the serologic response].
AB - BACKGROUND: The objective of our study was to ascertain the prevalence of
different HCV genotypes between the hepatitis C patients in the health area of
Monforte de Lemos, Spain, as well as the possible influence of risk factors on
their distribution and their relation with hepatic disease and with the serologic
response. PATIENTS AND METHODS: We have studied 128 patients with hepatitis C. Of
these, 41 were intravenous drug users (IVDU), 19 had received transfusions, 7
were hemodialyzed and in 61 the risk factors were unknown. Antibodies against HCV
were detected by second-generation enzyme immunoassay (EIA) and confirmed by
immunoblot. RNA-HCV presence was studied by reverse transcription-PCR (RT-PCR),
and a reverse hybridization test of the amplifications was used for the
genotyping. RESULTS: Hepatitis C genotypes 1b (46.1 [8.6%]), 1a (23.4 [7.3%]) and
3a (13.3 [5.9%]) were the most frequently encountered genotype. Genotype 1a (48.8
[15.3%]) was the most prevalent genotypes in IVDU patients, while 1b was the most
frequent in patients of unknown risk factors (62.3 [12.1%]). Alanine
aminotransferase (ALT) was elevated in 66.6 (17.7%) of patients with genotype 1a,
in 87.5 (8.6%) of patients with genotype 1b (p = 0.0367) and in 94.1 (11.2%) of
patients with genotype 3a (p = 0.0347). Subtype 1b was present in 6 of 7 cases of
cirrhosis (85.7%) and in 7 of 12 cases of active chronic hepatitis (58.3%). No
significant statistical differences were observed between the genotypes and the
specific IgM response against core antigen of HCV, neither we observed
differences in the serologic response against C1, C2, NS3 and NS4 peptides.
CONCLUSIONS: Hepatitis C genotypes 1a and 3a were the most prevalent genotypes
between IVDU patients while genotype 1b was the most frequent between non-IVDU
patients. Genotype 1b was associated to severe liver disease. Percentage of
positivity or the reactivity against HCV peptides was independent of the genotype
encountered in the patient.
PMID- 9656220
TI - [Factors associated with mortality and gait impairment in elderly patients with
hip fractures].
AB - BACKGROUND: Hip fractures are a major source of mortality and morbidity among the
elderly. The aim of the present study is to try to identify predictors of death
and of non-deambulation during the period of acute treatment. PATIENTS AND
METHODS: Consecutive prospective study of 459 patients older than 65 years
admitted to our hospital with acute proximal femoral fractures with 12 months
follow-up. RESULTS: The mean length of hospital stay was 26.6 days, it exists a
highly percentage of non-ambulatory patients at discharge from hospital (44.3%),
a low percentage of mortality in the immediate postoperative period (6.1%) and a
larger percentage of mortality at 6 months (26.15%). Factors associated with risk
of death at hospital are male sex (OR = 2.38; 95% CI = 1.04-5.47), deteriorated
mental status (OR = 2.62; 95% CI = 1.01-6.76) and no previous personal
independence (OR = 3.16; 95% CI = 1.19-8.38). Age over 80 years (OR = 2.27; 95%
CI = 1.43-3.60), deteriorated mental status (OR = 7.90; 95% CI = 3.83-16.3), no
walking ability before fracture (OR = 3.72; 95% CI = 2.33-5.91) and type of
fracture (OR = 1.84; 95% CI = 1.15-2.95) are shown as the determinants of gait
capacity. CONCLUSIONS: Mortality in the immediate postoperative period is
associated with sex, dementia and previous personal independence. The hospital
stay is extended and functional recovery at discharge is low, therefore, new
programs for these patients should be considered.
PMID- 9656221
TI - [Relationship of increased body weight, androgens, insulin and family history of
hypertension with blood pressure in premenopausal women].
AB - BACKGROUND: The aim of this study was to evaluate whether the body weight
increased, the androgens, the insulin and the family history of hypertension were
independently associated with hypertension. PATIENTS AND METHODS: Sixty-two
premenopausal women aged 42 y, whose did not have any situation that change the
variables to study: blood pressure, body mass index (BMI) and her increase since
age of 20, waist to hip ratio, family history of hypertension, smoking, alcohol,
exercise, fasting and after oral glucose tolerance test (GTT) glucose and
insulin, sex hormone binding globulin (SHBG), serum and salivary testosterone and
the free testosterone index. Hypertension was defined as blood pressure > or =
140/90 mmHg. Multivariate analysis and prevalence odds ratio was calculated.
RESULTS: Diastolic blood pressure correlated positively with BMI, waist to hip
ratio, increase of BMI, GTT glucose, fasting and GTT insulin, free testosterone
index and negatively with SHBG. Systolic blood pressure was only positively
correlated with GTT glucose. Into a logistic regression model, the increase of
BMI (OR: 1.23; IC: 95%: 1.04-1.5), the family history of hypertension (OR: 7.6;
IC 95%: 1.9-29.9) and the free testosterone index (OR: 1.7; IC 95%: 1.1-2.6) were
the only variables independently associated with hypertension. The prevalence
odds ratio of hypertension according to the presence or not of family history of
hypertension decreased when highest increase of BMI was considered. CONCLUSIONS:
Higher free testosterone levels with body weight increased in adulthood and
family history of hypertension are independent predictors of hypertension in
premenopausal women, whereas fasting insulin levels may be related to family
history of hypertension.
PMID- 9656222
TI - [Creutzfeldt-Jakob disease: an epidemic of the 21st century?].
PMID- 9656223
TI - [Economic evaluation of drugs: practical applications for the different deciding
agents].
PMID- 9656224
TI - [Instrument for the measure of quality of life in cancer patients].
PMID- 9656225
TI - [76 Year-old woman with tumor in the vertebral cervical spine].
PMID- 9656226
TI - [Torsade de pointes secondary to treatment with pentavalent antimonial drugs].
PMID- 9656227
TI - [The use of factorial analysis in the evaluation of transcultural equivalence in
questionnaires].
PMID- 9656228
TI - [Carbon monoxide poisoning].
PMID- 9656229
TI - [Mooren's corneal ulcers associated with hepatitis C].
PMID- 9656230
TI - Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves
scopolamine-induced amnesia in rats during the Morris water maze task.
AB - The effects of single and repeated administrations of ipidacrine (NIK-247, 9
amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride
monohydrate) on scopolamine-induced spatial learning deficit were investigated in
rats using the Morris water maze task. A single oral administration of ipidacrine
(0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in
this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for
5 successive days reduced the increased total latency induced by scopolamine to
the levels of the saline-treated control rats in this task. In this pharmaco
kinetic study, ipidacrine was rapidly taken up into the brain within 5 min.
Moreover, higher drug levels were observed mainly in the cortex and hippocampus,
which both play important roles in learning and memory. Thus, a previous study
together with this investigation indicate that ipidacrine improves amnesia which
consists of the impairment of the working and reference memory in various animal
models, suggesting that ipidacrine is a useful candidate for the therapy of
patients with Alzheimer's disease.
PMID- 9656231
TI - Effects of early postnatal AF64A treatment on passive avoidance response and
radial maze learning in rats.
AB - In order to investigate how the selectively lesioned cholinergic system at the
early postnatal age influences adult learning behavior, the effects of postnatal
administration of ethylcholine mustard aziridinium ion (AF64A), a selective
cholinergic neurotoxin, on the acquisition of 2 kinds of learning tasks were
examined. Rat pups received an intraventricular injection of AF64A (1.0 or 2.0
nmol) or saline on postnatal day 8, and in adulthood (at 3 months of age), they
were tested with the acquisition of passive avoidance response (PAR) and 8-arm
radial maze learning. In PAR testing, a significant impairment was observed in
male AF64A-treated rats. In addition, in the radial maze task, AF64A-treated rats
needed significantly more trials to acquire the task as compared with saline
treated animals. Histological examination after behavioral testings revealed a
marked reduction of acetylcholinesterase-stained fibers in the hippocampus and
dentate gyrus of the AF64A-treated groups, while there were no detectable changes
in the striatum or cerebral cortex. The results suggest that early postnatal
AF64A administration induced learning deficits in adulthood which were associated
with long-lasting cholinergic denervation in hippocampal formation.
PMID- 9656232
TI - [Pharmacokinetics of haloperidol in patients on hemodialysis].
AB - Psychotic symptoms among patients receiving hemolytic dialysis (HD) are quite
common, while studies showing pharmacokinetics and clearances of neuroleptics in
such patients are few. In such instances, previous studies recommended a single
administration of neuroleptics with about 1/3 to 1/2 of the normal dose for
patients without renal failure. We made a study of 4 cases of delirious patients
receiving HD and investigated the relationship between a daily dose of
haloperidol (HP), its blood concentration and changes of delirium symptoms before
and after HD. Oral or intravenous doses of HP (12-24 mg) were required for the
improvement of delirium. Blood concentration increased in proportion to the HP
dosage in all patients, and its average was significantly higher than that of the
control group. Approximately 25% of clearance was found before and after HD.
These studies suggest that the HP dosage for HD patients needs to be larger than
previously assumed. Changes in the pharmacokinetics of HP in HD patients seemed
to be influenced by a variety of factors such as binding rate with blood serum
albumin and HP, metabolic pathway of HP, and sensitivity of HP in the brain.
PMID- 9656233
TI - [Mitochondrial benzodiazepine receptors (MBR) in association with neurological
disorders].
AB - Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor
(PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model
of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50%
higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction
(i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL
mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear
responses similar to those increased in DDY mice after PBR stimulation,
suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice.
In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial
membranes and, possibly as a consequence of this, raised intracellular Ca2+.
Finally, we propose that MBR could be a major target of therapy for various
neurological disorders, so drugs such as "mitochondrial membrane stabilizers"
should be developed.
PMID- 9656234
TI - [Recent advances in Alzheimer's disease research].
AB - Vascular dementia (VD) and Alzheimer's disease (AD) are two main causes of
dementia in the aged. Recent epidemiological studies in Japan indicate that the
incidence of AD is becoming slightly higher than that of VD. Among various
approaches to clarify the etiology of AD, research through the mechanism of
formation of senile plaque and neurofibrillary tangle, which characterize AD
pathology, seems to be the most orthodox as well as fruitful. Genetic studies on
hereditary AD reveal that the etiologies of AD are heterogeneous, but the
deposition of beta amyloid followed by the accumulation of abnormally
phosphorylated tau-protein seems to be the common process specific to AD. In
regards to the clinical problems of AD, development of the diagnostic markers for
early definite diagnosis and effective therapeutic agents is most urgent. The
index of A beta 40/A beta 42 x tau calculated from measurements of A beta and tau
levels in cerebrospinal fluid is the best marker at present. On the other hand,
many antidementia drugs are now on trial. Most of them are acetylcholine
stimulating agents, including tacrine and donepezil, which have been admitted
recently in the USA and some other countries. Such drugs which suppress the
development of AD should be called true antidementia agents, but the present
drugs are not true antidementia drugs.
PMID- 9656235
TI - [Motor and cognitive functions of the basal ganglia].
AB - Basal ganglia have been known as a motor center because their lesions cause motor
disturbances in involuntary movements such as chorea, ballism or akinesia in
Parkinsonism. The different types of involuntary movements are closely related to
the underlying muscle tone. Mechanisms of bradykinesia or akinesia have been
elaborated in physiological studies on Parkinson's disease, and the significance
of sensorimotor processing or attention, arousal has been disclosed as a relevant
factor of bradykinesia. Cognitive functions of the basal ganglia have attracted
attention, particularly in the disorder of Parkinson's disease. Subcortical
dementia, difficulty in formation or changes of concepts, is encountered in
advanced stages of Parkinson's disease. Whether cognitive functions in the
frontostriatal system are primarily related to the motor function of the brain is
an issue for future study.
PMID- 9656236
TI - [Postsurgical adjuvant immunotherapy against primary non-small cell lung cancer].
AB - The prognosis of lung cancer patients is generally poor even when they have
undergone complete resection of primary tumors and systemic lymph node
dissection. This is mainly attributed to micrometastases which have already
developed by the time of surgery and the fact that local therapies cannot
eliminate all cancer cells from the body. We developed a multimodality
combination therapy for primary non-small cell lung cancer consisting of surgery,
chemotherapy, and adoptive immunotherapy using interleukin 2 (IL-2) and
lymphokine-activated killer (LAK) cells. The results of a randomized study
indicated that the survival rate of the IL-2, LAK adoptive immunotherapy group
was significantly higher than that of the control group. In conclusion, IL-2, LAK
adoptive immunotherapy is an effective and promising modality which will
compensate for the deficiencies of other therapies.
PMID- 9656237
TI - [Therapy for non-small cell lung cancer: new concepts based on molecular
biology].
AB - Recent advances in molecular biology have broadened our knowledge of the
biological characteristics of cancer. In the present paper, we review and discuss
new modalities of therapy for non-small cell lung cancer (NSCLC) based on
biological findings. These modalities include: 1) diagnosis of cancer based on
gene abnormalities: 2) decision making on chemo-/radiotherapy based on new
biological findings: 3) gene therapy: and 4) new chemotherapeutic agents.
Mutation of the p53 gene, which occurs most frequently in NSCLC, is a well
documented molecular target in these modalities. The development of polymerase
chain reaction technology has enabled early diagnosis of NSCLC by detection of
p53 gene abnormalities in sputum. Transfer of the wild-type p53 gene using a
retrovirus vector to cancer tissues with mutant p53 gene has already been tested
clinically. Inhibition of tumor neovascularization has been studied extensively
in attempts to develop noveal chemotherapeutic agents. Angiostatin or endostatin,
an inhibitor of tumor neovascularization is in clinical use. Matrix
metalloprotease inhibitions (MMPs) also inhibit neovascularization of tumors.
Marimastat, an oral MMP, is expected to prevent cancer metastasis.
PMID- 9656238
TI - [Does induction therapy followed by surgery improve the survival rate in limited
stage small-cell lung cancer patients?].
AB - Small-cell lung cancer (SCLC) is distinguished from non-small cell lung cancer
(NSCLC) by its rapid tumor doubling time, high growth fraction, and early
development of widespread metastases. Surgery alone offers the best chance for
long-term survival in selected patients with stage I SCLC. Most patients with
limited SCLC (stage I-IIIa) are treated with "comprehensive therapy" combined
with chemotherapy, radiotherapy (thoracic radiotherapy and/or prophylactic
cranial irradiation), and surgery. Although the efficacy of surgery in the
control of local disease is well established, to date no report has shown better
survival rates in patients who receive induction therapy when compared with
patients receiving postoperative chemotherapy. However, studies of induction
therapy include more patients with advanced-stage cancer than do studies of post
operative chemotherapy. Thus the final role of induction therapy followed by
surgery must await the results of future prospective, randomized trials conducted
by large cooperative study groups.
PMID- 9656239
TI - [Surgical treatment for metastatic lung tumors].
AB - Surgical treatment for metastatic lung tumors has been reported to be efficacious
in selected patients by many authors. Most of these reports are retrospective
studies. In our hospital, metastatic lung tumors were resected in 624 patients,
and the 5- and 10-year survival rates after pulmonary metastatectomy were 38.3%
and 26.6%, respectively. There are many long-time survivors without recurrence
after thoracotomy. However, pulmonary metastatectomy seems to offer no survival
benefit in some cancers, e.g., gastric cancer, even if the patients satisfy the
criteria for surgery. Prospective studies for each type of primary cancer are
needed to determine the true efficacy of pulmonary metastatectomy.
PMID- 9656240
TI - [Surgical treatment for multiple bilateral pulmonary metastatic tumors].
AB - To date, 162 patients with metastatic pulmonary tumors have undergone surgical
treatment in our institute (93 carcinomas, 51 sarcomas, 17 germ cell tumors, 1
melanoma). Of these, 57 and 105 had solitary and multiple lesions, respectively,
at their first surgery. Five of 57 patients developed additional lesions later.
The incidence of multiple pulmonary metastases was higher in sarcoma than in
cancer patients, and the prognosis after surgical treatment was found to be
significantly better in cancer than in sarcoma for patients with multiple
lesions. However, no significant difference was observed between the survival of
those with solitary and multiple lesions. The number of lesions found at surgery
was greater than that calculated based on preoperative chest CT scans, and the
discrepancy was greater when lesions exceeded 10 in number. However, the increase
in the number of metastatic lesions found did not affect the surgical results.
There was also no statistical difference in survival between patients with
bilateral and unilateral lesions. In contrast, those who underwent complete had a
significantly better prognosis than those who underwent incomplete resection at
surgery.
PMID- 9656241
TI - [Treatment for thymus-related malignant tumors].
AB - Surgery is the first-line therapy for thymoma. Postoperative radiotherapy should
be given for all invasive thymomas, followed by chemotherapy in some cases. Even
if the resection is not complete, surgery is effective therapy because most
thymomas are local and slow growing. Multidrug chemotherapy including cisplatin
is effective against thymoma. Thymic cancer is histologically varied. Surgery is
only one effective therapy for thymic cancer. Although no definitive chemotherapy
regimen for thymic cancer has yet been established, we feel that the cisplatin,
doxorubicin, cyclophosphamide, vincristine 4-drug combination regimen is
effective in thymic cancer patients. Seminoma out of mediastinal germ cell tumor
(GCT) is expected to have a good prognosis after surgery and radio-/chemotherapy.
Although the prognosis for those with nonseminomatous GCT has recently improved
due to chemotherapy and surgery, it is still poor.
PMID- 9656242
TI - [Treatment of non-thymic malignant tumors of the mediastinum].
AB - Nonthymic malignant tumors of the mediastinum are quite rare. Primary mediastinal
malignant lymphomas, malignant mediastinal neurogenic tumors, and primary
malignant mediastinal mesenchymal tumors are reviewed and discussed in terms of
the problems in their treatment.
PMID- 9656243
TI - [Therapeutic strategy for pleural mesothelioma].
AB - Generally pleural mesothelioma is divided into two histologic types: localized
and diffuse. Most cases of the former are considered to be benign and the latter
malignant. The treatment strategy for these tumors has been investigated,
including various surgical and chemotherapeutic approaches. In spite of these
efforts. no curative method for malignant mesothelioma has been established yet,
although the gene therapy is expected to be the most powerful tool in the near
future.
PMID- 9656244
TI - [Chest wall reconstruction after resection of malignant chest wall tumors].
AB - Full-thickness chest wall resection is performed for complete removal of primary
and secondary malignant chest wall tumors. Large defects of the chest wall after
resection must be repaired to maintain adequate ventilation, to protect important
intrathoracic structures, and to preserve cosmetic integrity. Various materials
have been utilized over the years to replace the rigid chest wall. At present,
Marlex mesh and a composite of Marlex mesh and methylmethacrylate are frequently
used to reconstruct rigid chest wall defects. On the other hand, to replace the
soft part of the chest wall and cover the rigid materials, pedicled muscle flaps,
myocutaneous flaps, or omentum are used. Major pedicled flaps include the
pectoralis major, rectus abdominis and latissimus dorsi muscular, and
musculocutaneous flaps. Techniques are now available to repair any chest wall
site, and to restore chest continuity in patients whose tumors are curatively
resected.
PMID- 9656245
TI - [Functional significance of p53 gene mutation in astrocytic neoplasms].
PMID- 9656246
TI - [p16 tumor suppressor gene alteration in brain tumors].
PMID- 9656247
TI - [Abnormalities of the EGF receptor gene in brain tumors].
PMID- 9656248
TI - [NF2].
PMID- 9656249
TI - [A puzzle with more pieces?: entering an era with a handful of glioma suppressor
genes].
PMID- 9656250
TI - [Vertigo and dizziness related to platelet aggregability].
AB - Platelet aggregates were measured in 82 cases with vertigo and dizziness and 60
cases with additional symptom of headache (so-called cervical vertigo). Results
showed that patients with vertigo and dizziness had increased aggregability and
patients with cervical vertigo were within normal range (p < 0.0001). 53 cases of
these with vertigo and dizziness were administrated platelet aggregation
inhibitors (mainly ticlopidine). After 1 approximately 2 weeks, most of patients
became symptom free, and at this time platelet aggregates of these patients were
suppressed to within normal range. Then patients were followed with chronological
measurements of platelet aggregates. During this time, aggregabilities were
attempted to be kept within the normal range, thus dose of platelet aggregation
inhibitor was controlled depending on the result of aggregability. Also patients
were encouraged to show good drug compliance by being informed of sudden
increasing aggregability. One patient experienced recurrence of vertigo after
ceasing the medicine. This study demonstrates that platelet aggregation may
increase in most of patients with not only vertigo but also dizziness in whom
administration of a platelet aggregation inhibitor is effective. It also stresses
that chronological measurements of platelet aggregations are important to control
the dose of medication.
PMID- 9656251
TI - [Diffusion-weighted MRI detectability of acute cerebral ischemia: comparison with
eventual infarction].
AB - To clarify the clinical significance of diffusion-weighted magnetic resonance
imaging (DWI) hyperintensity in acute cerebral ischemia, 34 patients were
investigated with cerebral ischemia that had lasted no more than 8 hours. Either
a spin echo sequence with navigator echo (n = 21) or an echo planar sequence (n =
13) was used for DWI using 1.5 tesla magnet. The eventual infarction was judged
from T2-weighted image (T2 WI) or CT performed 2-12 days after the onset and was
classified into cortical (n = 24) or perforating artery (n = 10) area. The
eventual infarction was compared in size with the acute DWI finding and expressed
as larger, same or smaller. Thirty patients showed ischemic hyperintensity
lesions on acute DWI (6 patients on T2 WI). In cortical artery areas, the
eventual infarction was same as hyperintensity area of acute DWI in 15 cases,
larger in 8 cases, smaller in 2 cases. In perforating artery areas, the eventual
infarction was same as hyperintensity area of acute DWI in 8 cases, and larger in
2 cases. These results suggest that in the perforating artery areas, the acute
DWI hyperintensity is a good predictor of the eventual infarction and that in
cortical artery areas, dynamic ischemic process may continue for hours before
resulting in the eventual infarction.
PMID- 9656252
TI - [Caregiver burden in dementia: evaluation with a Japanese version of the Zarit
caregiver burden interview].
AB - BACKGROUND AND PURPOSE: Dementia patients need assistance or supervision in their
daily activities. This often places a major burden on their caregivers. The
caregiver burden is reportedly a critical determinant for negative caregiving
outcomes. However, in Japan, no study evaluating the burden experienced by
caregivers for patients with established dementia diagnosis with a standardized
instrument has been carried out. The Zarit Caregiver Burden Interview (ZBI) is a
standardized, validated, reliable tool for assessment of the burden of caregivers
for dementia patients, and has been used in many studies in North America. In
this study, we arranged a Japanese version of the ZBI and applied it to
caregivers who were caring dementia patients. After examining the reliability and
validity of this version, we then studied a relationship between patients'
impairments and caregivers' burden. SUBJECTS AND METHODS: Subjects were 117
dementia patients. Diagnosis of dementia was made through extensive examinations
including MRI and PET/SPECT of the brain and based on appropriate clinical
diagnostic criteria of each disorder, which included Alzheimer's disease (n =
76), frontotemporal dementia (n = 10), vascular dementia (n = 11), progressive
supranuclear palsy (n = 3), corticobasal degeneration (n = 5), dementia with Lewy
bodies (n = 11), and normal pressure hydrocephalus (n = 1). The patients included
80 women and 37 men; the mean age was 72.3 +/- 7.7 (SD) years. Trained nurses
interviewed a principal caregiver of each patient by using the ZBI. The
caregivers included the patients' spouses (n = 62), offsprings (n = 17),
offspring's spouses (n = 37), and sibling (n = 1). Cognitive, functional, and
neuropsychiatric impairments and severity of dementia were assessed with
standardized instruments of the Mini-Mental State Examination (MMSE), Hyogo
Activities of Daily Living Scale (HADLS), Neuropsychiatric Inventory (NPI), and
Clinical Dementia Rating (CDR), respectively. RESULTS: The mean total ZBI score
was 28.6 +/- 15.3 (SD), the Personal strain (PS) score was 17.4 +/- 8.9, and Role
strain (RS) score was 6.5 +/- 5.7. All three scores had high Cronbach's alpha
coefficients (Total: 0.88, PS: 0.78, RS: 0.80) and had high Pearson's correlation
coefficients with a single global rating of burden (Total: 0.69, PS: 0.65, RS:
0.60). All ZBI scores were significantly correlated with MMSE, CDR, HADLS, and
NPI scores. A stepwise regression analysis revealed only the HADLS score and NPI
score as significant predictors of ZBI scores. CONCLUSIONS: This Japanese version
of the ZBI has a sufficient reliability and validity comparable to those reported
for the original version. Our results suggested that the patients' functional and
neuropsychiatric impairments were main patient's factors to increase the
caregiver's burden.
PMID- 9656253
TI - [Visual defect due to chiasmic compression by the A1 portion of the anterior
cerebral artery].
AB - Unilateral nasal hemianopia is highly difficult to notice with bilateral vision
intact, and only a few cases has been reported. There are several reported cases
of quadrantic hemianopsia caused by cerebral lesions, but the defects were found
bilaterally in all cases. There is only one reported case of which an aneurysm
was believed to be the cause. We confronted 3 cases of unilateral nasal
quadrantic hemianopia. In either case no ophthalmologic disorders could be found
but magnetic resonance imaging revealed the compression of the optic chiasma by
the A1 portion of the anterior cerebral artery. All three cases are presently
under conservative therapy and receive routine evaluations. Nerve fibers from the
upper and lower areas of the retina are routed complicatedly in the optic nerve
in the periphery of the optic chiasma. From the presentation of the quadrantic
hemianopia and from the radiological findings, we diagnosed that the visual
defect was caused by vascular compression of the optic chiasma.
PMID- 9656254
TI - [High uptake on 11C methionine PET scan in the pituitary gland of a patient with
cerebral glioma after surgical abortion].
AB - Positron emission tomography (PET) with various tracers provides physiologic and
biochemical information of living organs. Since radiologic examinations are
usually avoided in pregnant women, mainly because of the radiation risk to the
fetus, little is known about the effect of pregnancy on cerebral blood flow and
metabolism. This paper reports findings of a 11C methionine PET scan of the
pituitary gland in a woman after an abortion. The patient was a 31-year-old woman
who suffered a seizure in the 9th week of her second pregnancy. On admission,
computed tomography showed an abnormal mass lesion in the right frontal lobe, and
a brain tumor was suspected. The patient and her family asked that that pregnancy
be terminated. Seven days after a surgical abortion, methionine PET was
performed. The scan showed high methionine uptake in the pituitary gland as well
as in the right frontal lobe tumor. We suspected that another tumor was present
in the pituitary gland. The right frontal tumor was partially resected, and
pathologic examination of the resected specimen showed an astrocytoma (grade 2).
After the operation, the patient received 50 Gy irradiation and chemotherapy. Two
months after the operation, we performed a second methionine PET scan, which
showed high uptake in the residual right frontal tumor but not in the pituitary
gland. Results of other radiologic studies of the pituitary gland were normal.
These findings suggest that the transport of 11C methionine into the pituitary
gland may increase during pregnancy. Moreover, the pituitary gland of pregnancy
should be a part of the differential diagnosis of pituitary adenomas in PET
scanning. The change in physiologic uptake by the female pituitary gland should
be taken into account in the diagnosis of pituitary adenoma with methionine PET.
PMID- 9656255
TI - [A case of hypertrophic cranial pachymeningitis associated with intramedullary
lesion developed seizure marching from right lower extremity].
AB - A case of hypertrophic cranial pachymeningitis associated with intramedullary
lesion was reported. A 57-year-old male presented with the symptoms of Jacksonian
seizure and weakness of right lower extremity. Neurological examination showed
weakness and muscular atrophy of right lower extremity (MMT 1-2) and
hyperreflexia. Superficial sensation and position sense were normal, however
cortical sensory disturbance was recognized in his right lower extremity. MRI
revealed diffuse dural thickening with gadolinium enhancement in the left
convexity and hyperintense lesion in the bilateral (left dominant) frontal to
parietal lobe on T2 weighted image. Magnetic resonance angiography (MRA) and
digital subtraction angiography (DSA) showed occlusion of the superior sagittal
sinus. Histological examination revealed extensive fibrous tissue with
lymphocytes infiltration around the vessels. The cause of the intramedullary
lesion in this patient may have been related to the occlusion of superior
sagittal sinus, due to thickening dura mater and influence of inflammation.
PMID- 9656256
TI - Translation trouble.
PMID- 9656257
TI - Kava: an herbal sedative.
PMID- 9656258
TI - Pharmacologic management of depression in the elderly.
AB - Depression, the most common geriatric psychiatric disorder, is a disabling mood
disorder that impairs one's well-being and may even threaten a sufferer's life.
Severely depressed elderly persons are more likely to kill themselves than
individuals in any other age group. However, geriatric depression is, for the
most part, a treatable and manageable illness. Antidepressant medication can be
very effective in treating major depressive disorder (MDD). Because age-related
physical changes in the elderly produce pharmacokinetics that are often different
than that experienced by younger adults, different doses are often necessary.
This article summarizes recommendations for selecting and initiating appropriate
antidepressant therapy in elderly persons suffering from MDD. The benefits and
drawbacks of tricyclic antidepressant agents, and other atypical antidepressant
agents are discussed. Phases of treatment, drug selection, dosing, and
educational tips for pharmacotherapy are presented.
PMID- 9656259
TI - Focus groups reveal perils and promises of managed care for nurse practitioners.
AB - Decades of practice and research suggest that nurse practitioners (NPs) provide
cost-effective and high-quality care. Managed care's emphasis on prevention and
cost savings led some policy makers to view NPs as a way to meet the need for
primary care providers. However, access to and utilization of NPs has
increasingly been controlled by managed care organizations (MCOs) through their
selection of providers for primary care panels. This study employed qualitative
methodology to examine NPs' experiences with MCOs. Three focus groups, comprising
27 NPs in New York and Connecticut, revealed NPs' mixed reactions to managed care
and a range of sentiments regarding NPs' efforts to be listed as primary care
providers. The results reflected NPs' concerns about their perceived
"invisibility," as well as their sense of "invincibility" in the ways in which
NPs are responding to the barriers posed by MCOs. They identified barriers to, as
well as ways to facilitate, being listed by MCOs, and described the importance of
NPs working individually and collectively in negotiating with MCOs.
PMID- 9656260
TI - Diagnosis and management of gastroesophageal reflux in infants and children.
AB - Use of histamine blockers, proton pump inhibitors, and prokinetic drugs, along
with traditional antacids, has become standard therapy for gastroesophageal
reflux (GER) in symptomatic adults. Response to this therapy is assessed to
confirm the diagnosis of GER, and is often advocated as the best way to establish
the causes and effects of the disease. It is well documented that reflux occurs
throughout the life span. However, the incidence in children is difficult to
estimate, requiring interpretation of behavior and symptoms in nonverbal and
atypical presentations. Unfortunately, the diagnosis of GER in children is often
made after the development of complications such as aspiration pneumonia,
esophagitis, or ulcers. Early recognition and intervention by primary care
providers is necessary to prevent such serious complications of untreated GER.
This article presents the pathophysiology and clinical manifestations of GER.
Diagnosis in children is discussed, and recommendations for empiric therapy,
including conservative measures and drug therapies, are presented.
PMID- 9656261
TI - Promoting breast-feeding by managing common lactation problems.
AB - Breast milk is nutritionally and immunologically superior to any known
substitute. Morbidity and mortality are lower in breast-fed infants and their
mothers, resulting in better health and lower health care costs. Despite the
overwhelming evidence of health benefits and consequent endorsements from
professional groups, many health care providers do not actively promote breast
feeding initiation. They may actually undermine breast-feeding duration by
providing incorrect advice when problems develop. This article provides
recommendations for promoting breast-feeding and discusses diagnosis and
management options for common maternal lactation problems, including sore
nipples, eczema, candidal infection, and mastitis.
PMID- 9656262
TI - Primary care management of otitis externa.
AB - Otitis externa (OE) is an acute, painful inflammatory condition of the external
auditory canal that affects all age groups and accounts for about half of all
patients presenting with ear pain. Common causes are gram-negative bacteria,
Staphylococcus aureus, fungi, and dermatologic conditions such as eczema,
seborrhea, and psoriasis. Risk increases with prolonged exposure to heat and
moisture, especially in those who swim frequently or live in a tropical climate.
Treatment involves cleaning the canal thoroughly and instilling ototopical broad
spectrum antibiotics. Although OE is relatively benign and easy to treat in the
primary care setting, it can have life-threatening complications, especially in
diabetic and immunocompromised patients. This article reviews the differential
diagnosis, outlines treatment, and discusses preventive measures. A patient
education sheet is provided.
PMID- 9656263
TI - Common oral manifestations seen in patients with HIV/AIDS.
PMID- 9656264
TI - Effects of the Five-step Strategy with videotape modeling on performance of the
tennis serve.
AB - This study was designed to compare two methods of instructing Singer's Five-step
Strategy and their effect on the learning and performance of a tennis serve. 63
university students classified as recreational tennis players were stratified by
sex and then randomly assigned to one of three groups: Five-step Strategy with
videotaped modeling, audiotape Five-step Strategy plus written transcript, or no
strategy. Players performed seven blocks of 10 service attempts per block of
serves. Points accumulated with each service attempt as well as the number of
errors were the dependent measures. Separate 2-way analyses of variance were
conducted for each phase of the study. No significant pretreatment differences
were noted among groups. Further, all groups improved significantly across time
on both dependent measures and maintained this improved performance on a
subsequent retention test.
PMID- 9656265
TI - Golf clubs: hidden home hazard for children.
AB - Different accident patterns for golf equipment were noted for adults and
children. Children are more likely than adults to be hit by a golf club as
bystanders who entered the swing zone of a golf club. Previous publications
investigating accidents involving golf clubs and over 2000 incidents involving
emergency room treatment of children injured by golf clubs were reviewed. Most
injuries occurred when unsupervised children played with golf clubs at home. When
studies limit their focus to accident victims, who are currently being treated in
the emergency room, hospital, or outpatient facility, no deaths are reported. A
separate analysis of death certificates of children between the ages of 4 and 14
years also identified death as a possible consequence as 19 deaths have been
reported to the National Injury Information Clearinghouse. Based on these three
sources of data, golf clubs should not be used by children unsupervised given the
potential for serious and permanent head injury and death. Recommendations for
parents and manufactures regarding the safety of golf clubs are provided.
PMID- 9656266
TI - Relation between electrodermal- and visual-orienting responses and processing
resource allocation.
PMID- 9656267
TI - Competing personal goals and exercise behaviour.
AB - Research on the determinants of exercise behaviour has not assessed the role of
personal goals which may be in conflict with exercising. A cross-sectional study
showed that 312 nonexercisers, 466 people who exercised once or twice a week, and
202 people who exercised at the norm of at least three times a week differed
significantly with respect to the number of important personal goals expected to
be hampered by exercising at the norm. To be specific, the number of competing
activities in the home was higher for the sedentary group than for those who
exercised. Further, those who exercised at the norm reported fewer competing
social activities than all other subjects and fewer competing self-developmental
activities than the non-exercisers. Scores on the scale for activities outside
the home did not differ significantly among the three groups. It is argued that
any theoretical model of exercise behaviour should take into account the
influence of competing personal goals on the initiation and continuation of
exercise during leisure time.
PMID- 9656268
TI - Cognitive strategies and recall of pace by long-distance runners.
AB - The purpose of this study was to examine whether long-distance runners with high
or low performance of recalling running pace differed in their use of cognitive
strategies in a race. Recalling pace means the accuracy which runners have to
approach their self-set target pace in a race. 60 male competitive runners who
participated in a 20-km intercollegiate race were categorized as either runners
with high recall of pace (accurate) or the runners with low recall of pace
(inaccurate) on the basis of the discrepancy between a self-set target time and
actual time. Analysis showed that the 30 accurate recallers used the attention
strategies more frequently for recalling running pace, used the strategy of
following other runners less frequently, and set a more appropriate finish time
in accordance with their running ability than the 30 inaccurate recallers. The
accurate recallers, who monitored their running pace and fatigue by using
attention strategies, would reproduce more accurate self-set target times in
accordance with their running ability.
PMID- 9656269
TI - Cognitive, perceptual, and motor abilities in skilled basketball performance.
AB - The differences among athletes of differing skill should assist successful
identification and selection of the best athletes in a specific sport. For the
purpose of this study, a laboratory study was conducted with a group of 13 men on
the elite male national team of basketball players, 22 to 23 years of age, and a
control group of 15 men of equal age (physical education class) to assess
differences in their scores on cognitive skills (memory-retention, memory
grouping analytic ability), perceptual skills (speed of perception, prediction,
selective attention, response selection), and motor skills (dynamic balance,
whole body coordination, wrist-finger dexterity, rhythmic ability). Analysis
showed that elite male basketball players scored higher on hand coordination and
lower on dynamic balance given their anthropometric measurements. Elite players
were better on memory-retention, selective attention, and on prediction measures
than the control group. The above skills are important in basketball performance.
Researchers may examine whether other factors contribute more in the development
of perceptual and cognitive skills.
PMID- 9656270
TI - Auditory processing skills and hearing aid satisfaction in a sample of older
adults.
AB - The present study investigated the relationship between central auditory
processing skills and satisfaction with hearing aids in a hearing-impaired
geriatric sample of 58 adult wearers of hearing aids who were between the ages of
65 and 91 years. Analysis suggests the importance of adding central auditory
tasks such as compressed speech or dichotic listening tasks to the evaluation of
candidacy for hearing aids. This could lead to the better understanding of
satisfaction with amplification by the geriatric population.
PMID- 9656271
TI - Internal consistency of scores on Matching Familiar Figures Test-20 and
correlation of scores with age.
AB - Internal consistency of scores on the Matching Familiar Figures Test-20 and
patterns of latencies and errors were estimated for 337 boys and 287 girls
between the ages of 6 and 11 years, in the first five grades of primary school.
The Matching Familiar Figures Test-20 presented moderate coefficients of internal
consistency (.77) for errors and high coefficients (.94) for latencies. The
correlation between latencies and errors was moderate and significant (-.50).
PMID- 9656272
TI - Effects of magnetic stimulation through VLF-sferics on reaction time.
PMID- 9656273
TI - Effects of conditioning on physical fitness and club head speed in mature
golfers.
AB - The purpose of this study was to evaluate the effects of an 8-wk. conditioning
program on selected measures of physical fitness and golf performance for 12 male
and 5 female recreational golfers (M age = 52.4 yr., SD = 6.7 yr.). Measurements
were made at baseline and following the intervention. The twice-per-week program
consisted of strength training, flexibility, and plyometric exercises. Analysis
of the pre- and posttest scores showed that conditioning was associated with
significant increases in muscular strength, flexibility, and club head speed.
Without a control group, the data suggest conditioning may be a worthwhile
activity for mature golfers.
PMID- 9656274
TI - Sex, sport, situation, and competitive state anxiety.
AB - Within a multivariate design, the relationship between sex, sport, and
competitive situation with state anxiety was examined. The Competitive State
Anxiety Inventory-2 was administered to selected intramural basketball and
volleyball teams (ns = 266 and 226) prior to round-robin and play-off
competition. Multivariate analysis of variance yielded a significant interaction
of sport by sex and a significant main effect for sport. Follow-up tests
indicated that basketball players scored higher somatic and cognitive state
anxiety than volleyball players. Women scored higher on somatic and cognitive
state anxiety than men prior to play-off games. Results are discussed in terms of
importance of a multivariate approach to studying competitive anxiety.
PMID- 9656275
TI - Clothing preferences of older consumers.
AB - The study focused on identifying the apparel needs of older men and women in a
midwestern county. A survey technique was used to collect data on older peoples'
preferences for apparel including accessories, most preferred items, identified
similarity with previous apparel choices, and identification of buyer of the
apparel. Descriptive statistics were used to analyze the data. Implications of
the findings for future research and possibility of use by apparel designers,
manufacturers, and retailers are discussed.
PMID- 9656276
TI - Variation among nonclinical subjects on a line-bisection task.
AB - Absence of leftward bias in a line-bisection task is often used as a clinical
hemispheric indicator, but the effect is not uniform in a normal population. Sex,
handedness, and strategy variables affect the strength and direction of any bias.
PMID- 9656277
TI - Key components of the Mozart effect.
AB - The results of studies intended to replicate the enhancement of spatial-temporal
reasoning following exposure to 10 min. of Mozart's Sonata for Two Pianos in D
Major (K.448) have been varied. While some studies have replicated the effect,
others have not. We suggest that researchers' diverse choice of dependent
measures may account for these varied results. This paper provides a
neurophysiological context for the enhancement and considers theoretical and
experimental factors, including the choice of dependent measures, the
presentation order of the conditions, the selection of the musical composition,
and the inclusion of a distractor task, that may contribute to the various
findings. More work is needed before practical applications can be derived.
PMID- 9656278
TI - Body-type stereotyping in therapeutic judgments.
AB - 23 professional psychotherapists and 25 graduate student trainees rated line
drawings of three clients' body types on 21 clinically relevant personal
characteristics. Professionals and students alike rated ectomorphic and
endomorphic clients less favorably than mesomorphic clients.
PMID- 9656279
TI - Stimulus-response compatibility and position of the hands: nonadditive effects.
AB - An experiment was conducted using a two-choice stimulus-response compatibility
task factorially combined with position of the hands. Subjects responded to a
visual target word (Left or Right) by pressing on the left or the right key
depending on the compatible or incompatible assignment and performed the task
with the hands uncrossed or crossed. The effects of Stimulus-response
compatibility and Position of hands were not additive. Moreover, no effect of
compatibility occurred in the crossed-hand condition. These findings are
consistent with the predictions derived from a recent hypothesis assuming that in
some particular experimental conditions the presentation of the stimulus will
activate two automatic responses. The two stimulus-response compatibility
mappings related to these two automatic responses have been shown to be
positively or negatively correlated depending on the factorial combination of
Stimulus-Response Compatibility and Position of Hands. As a consequence the
effects of the two factors theoretically cannot be additive. This assumption
accounts for the present results.
PMID- 9656280
TI - Hallucinations.
AB - Hallucinations, sensory perceptions without environmental stimuli, occur as
simple experiences of auditory, gustatory, olfactory, tactile, or visual
phenomena as well as mixed- or complex experiences of more than one simple
phenomenon. The nature of the hallucination assists localization, differential
diagnosis, and treatment planning. In particular, the presence of persistent
visual hallucinations of persons with Parkinson's disease predicts dementia,
rapid deterioration, permanent nursing home placement, and death. Hallucinations
in persons with Alzheimer's disease are often associated with serious behavioral
problems and predict a rapid cognitive decline. Theories of the etiology of
hallucinations include (1) stimulation, e.g., neurochemical, electrical, seizure,
and ephaptic, and (2) inhibition, e.g., destruction of normally inhibitory
functions, resulting in disinhibition as in the Charles Bonnet and phantom limb
syndromes. Functional neuroimaging procedures suggest anatomical associations for
hallucinations. While hallucinations may be a symptom of medical, neurologic, and
psychiatric disorders, they may also occur in a wide range of human experiences.
PMID- 9656281
TI - Tobacco use and sport fandom.
PMID- 9656282
TI - Fatal alcohol-related traffic crashes increase subsequent to changes to and from
daylight savings time.
AB - On the hypothesis that sleepiness and alcohol interact to increase the risk of
alcohol-related traffic fatalities, the percentages of alcohol-related fatal
traffic crashes were assessed for the entire state of New Mexico for the years
1989-1992, for each of the seven days that preceded the changes to and from
Daylight Savings Time and for each of the 14 days which followed the changes to
and from Daylight Savings Time. Consistent with our hypothesis the percentage of
alcohol-related fatal crashes increased significantly during the first seven days
after these changes in Daylight Savings Time.
PMID- 9656283
TI - Feeding method and motor activity in 3-month-old human infants.
AB - It is currently acknowledged that breast-fed and formula-fed infants exhibit
different rates of physical growth. Little is known, however, about behavioral
differences that may be attributable to early feeding method. In the present
investigation, activity level in 3-mo.-old infants was examined by measuring
motoric output in 40 breast-fed and 40 formula-fed infants. Maternal ratings of
temperament did not differ across the two groups, but scores derived from the
actometer in a laboratory setting showed breast-fed infants to be more active.
Upper limb activity appeared to be particularly sensitive to feeding regimen.
Possible explanations for this effect as well as implications of these results
are discussed.
PMID- 9656284
TI - Additional developments regarding manifest dream structure and function.
AB - Detailed observation of manifest dream sequences indicated self-advocating
occurrences facilitating the dreamer's self interests, opposed by self
adversarial interferences. Further examination of manifest dream syntactical
structure additionally suggested a recurrent, four-step, algorithm for personal
problem-solving within an interpersonal matrix consisting of the following cycle:
(1) an opening scene setting the stage, (2) for the emergence of a self-concern,
(3) which evokes a strategy to deal with dreamer's self-concern, (4) that
eventuates in a consequence of the strategy. These steps repeat until the dream
ends. Observing these manifest dream structural features, attributable to
broadening past theorizing with "bottom-up" approaches, clarifies the dream's
problem-solving process by providing an empirical, observable framework for dream
interpretation and by contributing to their consensual validation.
PMID- 9656285
TI - Differences in several perceptual abilities between experts and novices in
basketball, volleyball and water-polo.
AB - The aim of this study was to examine differences between experts and novices in a
number of perceptual abilities. Three groups of elite athletes, 44 members of
Greek national teams in basketball (n = 12), volleyball (n = 13), and water-polo
(n = 19) were selected. Two groups of physical education students (ns = 18 and
21) were novices. The measured abilities were selected as the most important for
an elite athlete by expert coaches in the three sports. The four most frequently
selected abilities for each sport, according to the coaches' opinions, were
finally assessed. Analysis showed that differences were fewer than expected.
Basketball experts were better on prediction and selective attention. Volleyball
experts performed better on perceptual speed, focused attention, prediction, and
estimation of speed and direction of a moving object. Water-polo players had
significantly better scores than the novices on decision-making, visual reaction
time, and spatial orientation. It seems that the nature of each sport strongly
influences the way perceptual abilities differentiate elite athletes from
novices.
PMID- 9656286
TI - Effect sizes of mountains and molehills.
AB - Decisions about environmental aesthetics require valid, understandable
measurements of visual impacts. This study reports well known scientific
measurements (standardized mean contrasts) for well known images (mountains and
molehills). The scientific measurements of visual preferences for mountains and
molehills were 1.17 and -0.05, respectively.
PMID- 9656287
TI - Video-assisted cycling alters perception of effort and increases self-selected
exercise intensity.
AB - Two studies were conducted to assess whether indoor video-assisted cycling
influenced a person's quality of exercise (subjectively and quantitatively),
compared to indoor cycling alone. In the first study 12 recreationally active
subjects completed an initial test of VO2max, and three randomized trials of
cycling at 70% VO2max (35 min.) watching a commercial cycling tape (cycle video),
a test pattern displayed on the ergometer screen (blank video), or no video.
Subjects' ratings of perceived exertion (RPE) and Affect were recorded, and heart
rate and oxygen consumption (VO2) were measured during testing. The second study
required 12 different subjects first to complete an assessment of VO2max and then
two randomized trials (cycle video and no video) on a cycle ergometer where they
freely set the intensity of their own exercise. Measurements of VO2, heart rate,
blood lactate, power output, RPE, and Affect were recorded during testing.
Results of Exp. 1 indicated that subjects' perceived effort equally between the
two conditions, yet reported significantly (p < .05) higher affect at 25 and 35
min. of cycling during the cycle video condition than no video condition. Results
of Exp. 2 indicated that despite similar levels of blood lactate, subjects
exercised at a significantly higher intensity during the cycle video condition
compared to no video condition, with a higher VO2 and heart rate. The data
support the use of indoor exercise videos to improve the exercise experience and
also to increase the physiological demands of indoor exercise.
PMID- 9656289
TI - Subjective organisation in the recall of abstract body movements.
AB - Subjective organisation is a well known characteristic of verbal free recall in
that items are recalled in groupings known as "chunks" or "clusters." This
organisation is indicative of a memory strategy and has been used to derive the
cognitive structure of particular areas of knowledge. Clustering might also occur
in the free recall of body movements. Subjects attempted to learn unfamiliar
abstract body movements over five learning and recall trials. Analysis showed
that subjective organisation occurred and increased with additional recall
trials. This extends the clustering effect to the free recall of body movements.
It is suggested that this effect can be used to probe the cognitive structure of
motor memory.
PMID- 9656290
TI - Bulimia and perceived voice disorders: a preliminary study.
PMID- 9656291
TI - Implicit memory for odors: a possible method for observation.
AB - In an experiment 143 subjects were instructed to assign odors to contexts which
were displayed in a slide session. The slides depicted contexts from three areas
of everyday life which partly contained visual cues related to a presented odor.
After rating the fit of each odor to a context, the subjects rated the odors for
pleasantness. Analysis showed a strong influence of the visual cue on the rating
of fit for the contexts containing an odor-related visual element. In contexts
without a visual cue, rating of fit showed an influence of implicitly learned
memories of odor. The rating was not affected by the pleasantness of the odors.
The 1995 work of Schab and Crowder is critically reviewed, and results are
discussed within the framework of new, more ecologically oriented research on
memory for odor.
PMID- 9656292
TI - Some aspects of self-reported hand preference.
AB - The aim of the present study was to compare self-reported handedness with the
directly tested hand preference using a 10-item battery in sample of 1223
students. The question assessing self-reported handedness was whether you are a
left- or a right-hander or you use both hands equally. Responses indicate that
self-reported handedness is a crude but possible method of measurement. Female
right-handers showed the best agreement.
PMID- 9656294
TI - Body mass indexes and historical ratings of U.S. presidents: 1948-1984.
PMID- 9656293
TI - Fractionated premotor, motor, and ankle dorsiflexion reaction times in
hemiplegia.
AB - Ten hemiplegic subjects completed 20 rapid dorsiflexions of their afflicted and
nonafflicted limbs. Electrodes were attached to the tibialis anterior and the
gastrocnemius muscles and electromyograms were recorded for their premotor time,
motor time, and simple reaction time during ankle dorsiflexion and plantar
flexion of their lower limbs. The fractionated components of reaction time,
namely, premotor time and motor time, of both legs were statistically compared.
It was found that the premotor time of the subject's stroke-affected limb was
significantly slower than the premotor time of the nonaffected limb (control),
with no differences between their associated mean motor times. These results
supported the hypothesis that a stroke has a deleterious affect upon the central,
premotor time processing centers and has no disruptive influence upon the
peripheral motor time. Comparing the fractionated components of reaction time
(premotor time and motor time), with simple reaction time, the former provided a
more sensitive and valid method to detect possible injurious side effects of a
stroke upon the brain's neuromotor transmission centers and subcenters, and their
peripheral, stimulus, response network.
PMID- 9656295
TI - Influence of spatial mapping on manual aiming asymmetries.
AB - Two experiments were conducted to examine manual asymmetries in a one-dimensional
aiming task. In Exp. 1, 10 right-handed adults slid a computer mouse 13 cm on a
graphics tablet with both the right and left hands to targets of 3 different
diameters. Under these conditions, the movement time for the right hand was
significantly faster as expected. In Exp. 2, subjects performed similar movements
to move a cursor 13 cm on a computer monitor. Thus the study was identical except
the stimulus-response mapping was indirect. In this situation, there were no
significant difference for either movement time or movement error between hands
despite these performance measures indicating the target aiming was more
difficult in Exp. 2. Because increases in task difficulty generally result in a
greater advantage for the right hand, as indicated by Todor & Smiley, 1985, the
present studies suggest that superiority of the right hand in aiming tasks may be
diminished when spatial translation is required. Perhaps the spatial translation
requires greater involvement of the right hemisphere, a process associated with
manual advantage for the left hand, previously suggested by Roy and MacKenzie.
PMID- 9656296
TI - Benefits of providing cognitive performance strategies to novice performers
learning a complex motor skill.
AB - Verbal reports were collected from experienced performers during acquisition
trials of a novel throwing task and summarized as cognitive performance
strategies. These strategies were incorporated in the practice regimen of 8
novices with no sport experience who learned the same task. A control group of 8
novices practiced the task without the experts' cognitive performance strategies.
The performance of the novices who used the strategies was similar to that of the
experts and significantly better than the performance of the control novices.
PMID- 9656297
TI - Patterns of adaptation to conflict in bulimia and temporo-mandibular joint
disorder.
AB - Two age- and education-matched groups of 45 women, respectively, with the
diagnoses of Bulimia and of Temporo-mandibular Joint Disorder, were administered
the Serial Color-Word Test, to assess differences in the pattern of adaptation to
conflict (the latter being represented by the Stroop task). Three types of norms
(clinical, nonclinical and based on reading times) and the functions derived from
a previous cluster analysis were employed. Comparisons utilizing clinical norms
and cluster analytical functions did not significantly differentiate between
groups. According to both nonclinical norms and norms based on reading times, the
two clinical groups were significantly different concerning the distribution of
adaptation patterns. Bulimic patients resorted more often to the Dissociative
pattern (high nonlinear change of reading times), while temporomandibular
patients were characterized by the Cumulative pattern (high linear change) and,
secondarily, by the Cumulative-Dissociative pattern (high linear and nonlinear
change). Intergroup differences were more marked when employing the new norms
based on reading times.
PMID- 9656298
TI - Individual differences in the performance of highly learned skill.
AB - Examination of individual differences (intertrial correlations) of highly skilled
performance by professional golfers demonstrated that individuals respond to
conditions in dissimilar ways, despite having strong central tendency. Behavioral
scientists may benefit extraordinarily by heeding the advice of Cronbach and
Jones to combine differential and experimental techniques.
PMID- 9656299
TI - Assessment of memory in multiple sclerosis patients using the Memory Assessment
Scale.
AB - Previous assessment of memory function in multiple sclerosis patients has yielded
mixed findings regarding the type and severity of memory deficits, which may be
due to (1) differential selection of scales for memory assessment; (2) limited,
inconsistent or weak reliability and validity data for the memory scales
employed; (3) poor standardization techniques; (4) lack of theoretical foundation
for the measure; and (5) limited control of confounding variables, e.g.,
education, age and the use of nonverbal memory tests. The purpose of the present
study was to assess memory function in multiple sclerosis subjects using the
verbal subtests of the Memory Assessment Scale, a relatively new measure designed
to overcome many of the aforementioned problems. Participants included 57
patients diagnosed as relapsing-remitting, 47 diagnosed as chronic progressive
(two generally recognized types of multiple sclerosis), and 132 control
participants. A multivariate analysis controlling for age and verbal IQ was
significant (Wilks = 5.64, p < .001). One way follow-up tests showed both groups
with multiple sclerosis had significantly diminished performance across all
memory variables when compared with controls, with the exception of List
Clustering Acquisition. This indicated that the patients used clustering
(mentally grouping similar words together) as often as controls did. These
findings provide support for the presence of significant and consistent verbal
memory impairment in multiple sclerosis patients and the particular importance of
using psychometrically sound measures in the assessment of this population.
PMID- 9656300
TI - An attempt to distinguish between two reversal processing strategies for learning
modeled motor skill.
AB - The first purpose was to examine the effects of reversal processing strategy of
visual information on recognition and acquisition of a sequential gross movement
task. The second purpose was to examine the relationship between a measure of
reversal processing strategy and movements during eye fixation. 24 undergraduates
were assigned into one of three conditions, a Reversal-emphasized condition in
which subjects were instructed to recognize the movement correctly from a
reversed angle, a Recognition-emphasized condition in which subjects were
instructed to recognize the movement correctly, and a Recall-emphasized condition
in which subjects were instructed to reproduce the movement correctly. Subjects
observed stimuli with the model facing them. Following observation, the subjects'
recognition of stimuli was tested with model facing towards (Facing Angle) and
facing away (Rear Angle). Recall tests were carried out after the two recognition
tests. Analysis indicated that accuracy and response time on recognition tests
improved under each condition, but there were no other effects. The Reversal
emphasized condition showed significantly greater modeling effect than the other
conditions. Movements during eye fixation were very similar among conditions.
PMID- 9656301
TI - Comparing spatial abilities of collegiate athletes in different sports.
AB - Researchers indicated that androgen enhances spatial ability in women but
inhibits it in men. Since studies also indicate that athletes have higher than
normal levels of androgen, whether spatial perception scores differed for men and
women in different sports was examined. Spatial tests (visualization and
orientation) were given to 150 men and 150 women collegiate athletes in different
varsity sports. Analysis showed the women scored significantly higher than the
men. In basketball, a sport common to both sexes, women did significantly better
but this was not found in the other mixed-sex sports (baseball, swimming, and
track).
PMID- 9656302
TI - Interference as measured by the Stroop Color-Word Test and the Direction-Word
Test with varied comparison stimuli.
AB - The current investigation explored the influence of irrelevant stimuli on the
standard Stroop color-word effect. Also investigated is the effectiveness of a
new direction-related test which, unlike previous direction-related Stroop-like
measures, exactly parallels format of the original Stroop in administration. This
Direction-Word Test uses arrowheads at the ends of each target word to depict
direction, e.g., left, right, and middle. 92 undergraduate students volunteered
to participate. Analysis indicated that interference is found on the Color-Word
Test, even with noncolor words as stimuli. Interference also occurred on the new
Direction-Word Test. The correlation between the two forms of the Stroop effect
was low, although significant, perhaps indicating there are different systems
involved in response interference.
PMID- 9656303
TI - Public school speech-language pathologists' knowledge of sickle cell disease.
PMID- 9656304
TI - Combined effects of goal setting and performance feedback on performance and
physiological response on a maximum effort task.
AB - A laboratory experiment was conducted (N = 40 subjects) to examine whether goal
setting would be associated with reduced heart rate on an endurance task.
Participants performed an endurance task on an ergometer bicycle. One week later
when participants performed the task again half of them set a specific personal
goal for an increase in performance. Analysis indicated that subjects who set a
goal showed significant improvement in comparison with the control group.
Moreover, subjects in the goal group had a significantly lower mean heart rate
during the test and had a higher mean heart rate at the end of the test than on
the first trial. Results are discussed in terms of combining cognitive and
physiological explanations for the beneficial effects of goal setting on
performance.
PMID- 9656305
TI - Role of auditory temporal processing for reading and spelling disability.
AB - The role of auditory temporal processing in reading and spelling was investigated
in a sample of 30 children and one of 31 adults, using a gap-detection task with
nonspeech stimuli. There was no evidence for a relationship between reading and
spelling disability (dyslexia) and the gap-detection threshold. The results were
discussed regarding the relevance for the popular hypothesis of an auditory
temporal processing deficit underlying dyslexia.
PMID- 9656306
TI - Emotion and style in 30-second television advertisements targeted at men, women,
boys, and girls.
AB - A program for objective textual analysis which incorporated measures of style,
word emotionality, and word imagery, was used to score the verbal portion of 152
30-sec. television advertisements. This analysis indicated that advertisements
directed at children were more active, longer, and less negative than those
directed at adults. A comparison of advertisements directed at males and females
regardless of age showed greater linguistic complexity (more words, fewer common
words) when their text was directed at women and girls. Each of the 13 stylistic
and emotional measures used to describe advertisements produced at least one
significant difference associated with the age or the sex of the target
population or their interaction.
PMID- 9656307
TI - Some relationships among affection, aggression and alcohol abuse in the family
setting.
AB - Three questionnaire studies involving 101, 270, and 144 college students examined
the relationship between affectionate behaviors and aggressive behaviors in the
family environment as rated by the college students. Measures of affection and
aggression were significantly negatively associated in nearly all analyses.
Participants' ratings of parental alcohol abuse were positively associated with
measures of parental aggression and negatively correlated with measures of
parental affection.
PMID- 9656308
TI - Seasonal variations in melatonin may modulate glycemic response to exercise.
PMID- 9656309
TI - Replicated factor analysis of the Italian Version of the Body Image Avoidance
Questionnaire.
AB - A multisample factor analysis identified two different solutions, a 3-factor
solution from the high school sample of 439 subjects and a 4-factor solution from
both the university sample of 200 subjects and an obese sample of 142 subjects.
However, in the first sample Factor 1 included the same items which formed Factor
2 and Factor 4 in both the second and the third samples. This suggests that the
structure of the questionnaire can be adequately described by four different
factors. The analysis of the factor loading also indicated that six items should
be removed (Items 2, 3, 10, 11, 17, 19) from the Italian version.
PMID- 9656310
TI - Factor structure of the Italian version of the Body Satisfaction Scale: a
multisample analysis.
AB - The paper describes the factorial structure of the Italian version of the Body
Satisfaction Scale, a simple self-report questionnaire designed to assess
satisfaction with 16 body parts. The results suggest that the structure of the
questionnaire can be adequately represented by three different factors. Even if
this solution is different from the one obtained in the original English samples,
this interpretation was confirmed by a cross-validation on 806 subjects, a
clinical sample and two normal samples. This result may be useful for the
screening of subjects at risk for eating-disorders because it makes possible
prediction of targeted areas of dissatisfaction which is not generally possible
with other inventories. The analysis of the factor loadings also suggested that
three items should be removed (teeth, eyes, and ears) from the Italian version.
PMID- 9656311
TI - Prenatal alcohol exposure and communication, behavior, and nonverbal intelligence
of 3 school-age children.
AB - Associations of prenatal alcohol exposure in speech, language, behavioral, and
intellectual development were investigated in three school-aged children
diagnosed with Fetal Alcohol Syndrome, accompanied by Attention Deficit
Hyperactivity Disorder. Each child showed similar patterns of moderate-to-severe
dysfunctional behavior; however, their scores on speech, language and nonverbal
intellectual measures were highly variable.
PMID- 9656312
TI - The physioacoustic method and the creative process.
AB - This study investigated the physioacoustic chair's, i.e., an application of low
frequency sound waves, possible psychological effects with respect to deductive
thinking and creativity as well as its possible effect on heart rate. Subjects,
21 men and 21 women, were randomly assigned in equal numbers to three groups: a
control group, a placebo group, i.e., a group who believed that they underwent a
physioacoustic treatment program which they however did not undergo, and a
physioacoustic treatment group. After manipulation, subjects were required to
take three psychological tests (measuring fluency and originality, preconscious
thinking, and deductive thinking) in random order. During the entire experiment,
subjects' heart rates were registered every minute. Analysis showed no
significant differences among the groups with respect to psychological effects or
to heart rate. The results were interpreted to mean that the physioacoustic chair
provides a form of relaxation which does not produce effects on the creative
process.
PMID- 9656313
TI - Exercise dependence among competitive power lifters.
AB - Scores on exercise dependence examined among a sample of 14 competitive power
lifters showed higher exercise dependence among lifters than those previously
reported for endurance athletes.
PMID- 9656314
TI - Interferon beta 1-b in verbal memory functioning of patients with relapsing
remitting multiple sclerosis.
AB - The effects of interferon Beta 1-b (Betaseron) on verbal memory functioning was
examined in 167 patients with relapsing-remitting multiple sclerosis and 112
matched normal controls. Subjects were administered 10 verbal memory tests from
the Memory Assessment Scales and the Verbal subtests from the Wechsler Adult
Intelligence Scale. Analysis showed subjects treated with Betaseron (n = 73) did
not perform significantly better on measures of verbal memory or verbal ability
than subjects not receiving the drug (n = 94), although the mean performance of
treated subjects was higher across all verbal memory tests. Both groups of
patients performed significantly worse on verbal memory subtests measuring list
acquisition, delayed list recall, delayed cued recall, and the immediate and
delayed recall of names and faces than control subjects. Although patients had
lower performance scores across all memory tests than the control subjects, their
scores were not within the impaired range. These results do not permit a clear
conclusion about the effects of Betaseron on verbal memory for any effect is
probably obscured by the relatively preserved cognitive functioning of this
outpatient sample.
PMID- 9656315
TI - Connection between synchronization of oscillatory activities at early stages and
a final stage in the visual system.
AB - Singer's group and we found synchronized oscillatory responses at early stages
and at a final stage in visual processing, respectively. However, the former
occurs on a millisecond time scale and the latter on a second time scale. We have
considered that this results from a difference in scale of something which takes
part in the oscillations. From this viewpoint, here we first find suppression
effects on both figure and ground of a pattern and on only the ground in a
binocular-rivalry situation and then examine, using the effects of two steps,
what oscillates and synchronizes at the last stage for form. Finally, we conclude
that the synchronous neuronal oscillations depend on firing patterns of neurons
at early stages in the visual system and the psychophysical ones on
configurations of the spread effect of strength of pattern involved closely in
whole processing of the visual system and the latter originates in the former.
PMID- 9656316
TI - Licensure of adapted physical education teachers and undergraduates' attitudes
toward students with disabilities.
AB - This study compared attitudes of 816 undergraduates toward students with
disabilities by whether the state licensed teachers for adapted physical
education. Analysis indicated mean attitude scores in states with such licensure
were significantly more positive than in states working toward licensure and
those with none.
PMID- 9656317
TI - Multiple streams of time consciousness: a new model of retrospective timing.
AB - This note suggests a new hypothesis for retrospective timing, that, when one
experiences a period of time in which plural contexts progress simultaneously, a
stream of time consciousness is formed for each context and a temporal judgment
to the period is made for each of the streams. In the experiment, 17 subjects
observed an event in which plural contexts progressed simultaneously and
estimated the time a certain thing occurred during the event. Subjects' estimated
times varied with the number of changes in the context which the subjects were
required to judge. The hypothesis was supported.
PMID- 9656318
TI - Gene-environment interactions in the pathogenesis of type 2 diabetes mellitus:
lessons learned from the Pima Indians.
AB - The comprehensive longitudinal studies of diabetes conducted in the Pima Indians
of Arizona over the last 30 years indicate that both genetic and environmental
factors play a critical role in the pathogenesis of the disease. Pre- and
postnatal exposures as well as diet and physical activity in adulthood markedly
affect risk of developing NIDDM in this population. In addition, the high
prevalence of diabetes in the Pimas relative to other populations and the
familiality of the disease and its precursors, strongly suggest a substantial
genetic basis. Interactions between genes and the environment are obviously
important in the pathogenesis of NIDDM, but it remains unclear exactly how these
interactions occur and how to adequately account for these effects when searching
for genes contributing to diabetes. The realization that gene-environment
interactions are significant, and may be the dominant mechanism increasing
susceptibility to NIDDM, should encourage further investigations. Future progress
in studying the genetics of NIDDM and other complex diseases will come not only
from technical advances currently in development, but also from advances in
understanding the pathophysiology of the disease and the role of gene-environment
interactions, and a renewed emphasis on careful clinical characterization of
subjects participating in these studies.
PMID- 9656319
TI - Diet and cancer prevention: the concerted action polyp prevention (CAPP) studies.
PMID- 9656320
TI - Genetics, calcium intake and osteoporosis.
AB - Genetic factors explain a high proportion of the age-specific differences in bone
density, size and turnover. The potential for interaction between hormonal, diet
and lifestyle factors is likely to be important. Common allelic variation in the
VDR is an example of normal gene variants altering Ca homoeostasis, with effects
on body and bone size as well as bone density. The VDR findings suggesting
interactions between genetic and nutritional factors are an important target for
future research. These studies are complicated by the potential for effects of
gene-gene interactions and of undefined environmental factors. These problems
notwithstanding, considerations of environmental and nutritional contributions,
such as Ca intake and vitamin D status, will be critical in interpreting these
genetic pathways and in 'personalizing' nutritional recommendations.
PMID- 9656321
TI - Nutritional and hormonal regulation of hair follicle growth and development.
PMID- 9656322
TI - Nutritional and hormonal control of skeletal-muscle cell growth and
differentiation.
PMID- 9656323
TI - Nutrient regulation of intestinal proliferation and apoptosis.
PMID- 9656324
TI - Some aspects of the metabolic response to surgical trauma.
PMID- 9656325
TI - The role of nutrition and diet in rheumatoid arthritis.
AB - Given the lack of understanding of the nutritional requirements in RA, plus the
variability in its clinical course, it is difficult to produce specific dietary
recommendations for RA. In general, sufferers should consume as varied a diet as
possible, based on current Department of Health (1991) guidelines. Dietary
counselling is important to help patients achieve this. Self-imposed elimination
diets should be avoided and suspected food intolerance tested under strict
clinical supervision. Nutrient megadosing is inadvisable, although dietary
supplementation with Ca, vitamin D, folic acid or multivitamins and minerals
should be recommended where necessary.
PMID- 9656326
TI - The effect of prenatal diet and glucocorticoids on growth and systolic blood
pressure in the rat.
PMID- 9656327
TI - Nutrition, immunity and the fetal and infant origins of disease hypothesis in
developing countries.
PMID- 9656328
TI - Molecular biological approaches to nutrient-gene interactions.
PMID- 9656329
TI - Response of placental amino acid transport to gestational age and intrauterine
growth retardation.
PMID- 9656330
TI - Regulation of liver gene expression by glucose.
PMID- 9656331
TI - Modulation of immune function by dietary fatty acids.
PMID- 9656332
TI - Post-translational events in the intracellular transit of apolipoprotein-B:
modulation by dietary lipids.
PMID- 9656333
TI - Antioxidant micronutrients and gene expression.
PMID- 9656334
TI - A role of zinc in the regulation of gene expression.
AB - Zn, without question, has important functions related to gene expression. Newer
technologies applied to address these functions are providing answers relating to
the importance of this micronutrient in human and animal health.
PMID- 9656335
TI - Measuring food intake in farm and laboratory animals.
PMID- 9656336
TI - Measuring food intake in wild animals: primates.
PMID- 9656337
TI - Measuring intake in free-living human subjects: a question of bias.
PMID- 9656338
TI - The role of technology transfer in parasite control in developing countries.
PMID- 9656339
TI - Current status of food-borne parasitic zoonoses in South Africa and Namibia.
AB - Epidemiological data on food-borne parasitic zoonoses in countries of southern
Africa are sporadic. In a study of toxoplasmosis in South Africa, there was an
overall prevalence of 21% (2, 147/10,228). Prevalences vary between the different
cultural groups and from one geographical region to another. The prevalence rate
for the San (Bushmen) people of Namibia and Botswana was 9% (65/725) compared to
the 30% (190/635) found in the Indian and Black communities of Kwazulu-Natal
province, South Africa. These variations are probably linked to the dietary
habits of the different cultural communities. Cysticercosis appears to be most
prevalent in the Eastern Cape Province (former Transkei), where pigs roam freely
and sanitation facilities are inadequate or non-existent. Segments of tapeworms
often feature as an ingredient of concoctions prepared by traditional healers and
are suspected sources of many of the cases of cysticercosis in South Africa.
Trichinella nelsoni has been identified in wild game in South Africa: so far no
cases of infection in humans have been recorded. Cases of Sarcocystis have been
identified in some instances but infection is probably underdiagnosed in the
country.
PMID- 9656340
TI - Current status of gnathostomiasis dorolesi in Miyazaki Prefecture, Japan.
AB - Gnathostomiasis is an important food-borne parasitic zoonosis caused mainly by
ingesting uncooked or undercooked flesh of freshwater fishes. Although four
distinct species of the genus Gnathostoma were identified as the causative agents
for human gnathostomiasis, human infections with G. doloresi have been found only
in Japan, concentrated in Miyazaki Prefecture. So far we have found 25 cases in
Miyazaki Prefecture. Although most of these patients were of cutaneous
gnathostomiasis, two patients presented to the hospital with unusual clinical
manifestations; one case was a pulmonary gnathostomiasis diagnosed by
immunoserological methods, and the other was an ileus caused by migration of the
late 3rd stage larva in the colonic tissue, which was found by post-operative
histopathological examination. Although cutaneous lesions such as creeping
eruption or mobile erythema are the common clinical features of gnathostomiasis,
caution should be paid to the presence of such unusual cases.
PMID- 9656341
TI - Trichinella in arctic, subarctic and temperate regions: Greenland, the
Scandinavian countries and the Baltic States.
AB - The transmission and occurrence of Trichinella spp according to the zoogeography
of different climatic conditions, socioeconomy and human activity are discussed.
Comparing arctic, subarctic and temperate regions, it appears that the species of
Trichinella present, the composition of the fauna and the human activity are all
very important interacting factors affecting epidemiology. In Greenland, where
only sylvatic trichinellosis is present, the high prevalence in wildlife appears
closely connected with polar bear hunting. In the Scandinavian countries, the
prevalence of both sylvatic and domestic trichinellosis differ widely. Denmark is
regarded as Trichinella-free in the case of domestic trichinellosis and sylvatic
trichinellosis is very rare. In Sweden and Norway, Trichinella is found in
wildlife but domestic trichinellosis is rare. In Finland, both domestic and
sylvatic trichinellosis have increased dramatically during the last decade. Among
the Scandinavian countries, Finland also has the largest populations of
carnivorous mammals. In the Baltic states, Trichinella is frequently found in
wildlife and domestic trichinellosis is increasingly diagnosed. The high
prevalence in the widespread wildlife populations may have epidemiological
importance in relation to the recent changes in production and infrastructure in
these former Soviet states.
PMID- 9656342
TI - Tapeworm infection resulting from pork eaten at a wedding banquet.
AB - Forty-five people who had attended a wedding banquet were examined by means of
both Avidin-Biotin Peroxidase Complex-ELISA (ABC-ELISA) and Kato stool thick
smear technic. The results revealed that the positive rates with ABC-ELISA were
15.56% (7/45) and Kato Katz 0.62% (1/161). There was a significant difference
between the two positive rates (p < 0.005). Six people at the wedding had
taeniasis and 4 of them also had cysticercosis. Local people have no habit of
eating uncooked pork, but at this banquet the meat from an infected cysticerci
pig was used for preparing dishes for the wedding feast and the cold dishes were
contaminated by the bladder worms as the result of using the same chopping block.
PMID- 9656343
TI - A survey report--July 1993: cysticercosis in the Grand Dani Valley, Jayawijaya
District, Irian Jaya Province, Indonesia.
AB - A community survey was conducted in Gran Dani Valley, Jayawijaya District, Irian
Jaya Province, Indonesia. A total of 537 adults were asked whether they
experienced epilepsy, and were physically examined for cysticercosis cysts. Forty
eight percent experienced at least one attack of epilepsy. Men had attacks 2.5
times more often than woman. Cysticercosis cysts were found in 26.5% men having
4.6 times more cysts than women. The cysts were mostly found in the pectoral
region. The survey showed a raise cysticercosis in the Highlands of Irian Jaya
and is considered a public health problem. Treatment was not available, but
improvement of personal and environmental hygiene would be important. Mass de
worming activity should be a part of routine public health service in the
district.
PMID- 9656344
TI - Epidemiology of echinococcosis in Nepal.
AB - Echinococcosis and hydatidosis is a parasitic zoonotic disease of human and
animals. This disease has created public health and environment problems in all
urban areas of Nepal. Based on the three year study (1993-1995) it has been
revealed that the epidemiological cycle (indigenous) of Echinococcus granulosus
parasite is dog-pig-dog cycle and human acquire infection accidentally through
infected dog stool. However, this study has proved also the epidemiological cycle
like dog-sheep-dog, dog-goat-dog and dog-buffalo-dog. This study was supported by
International Development Research Centre (IDRC), Ottawa, Canada.
PMID- 9656345
TI - Epidemiology of paragonimiasis in Korea.
AB - In Korea, soybean-sauce soaked freshwater crabs (kejang) have been a favorite
delicacy when eating a bowl of rice. This traditional food has been a main source
of human paragonimiasis. Until the late 1960s, human paragonimiasis had been
prevalent; at least two million people had contracted the infection as determined
by intradermal tests. About 40% of these were egg positive. In the turmoil of the
green revolution and industrialization in the 1970s/1980s, ecological damage
occurred widely. In many streams, populations of snail and crustacean hosts were
reduced to levels almost of extinction. Population reduction of the intermediate
hosts was followed by lowered endemicity. Attitudes of people, changed during the
period, also reduced chances of paragonimiasis. Survey data in the 1990s
indicated that prevalence of human paragonimiasis has lowered to about one 100th
of that in the early 1970s. In a referral system, however, about one hundred
clinical cases have been diagnosed annually by antibody test (ELISA), undertaken
for clinical differentiation from tuberculosis. At least 10% of freshwater crabs
sold in local markets are infected with the metacercariae. Paragonimiasis control
has benefited in Korea mainly by the untoward effects of water pollution. To
place P. westermani infections as enzootic, health education and surveillance
systems should have a priority.
PMID- 9656346
TI - Pulmonary paragonimiasis and tuberculosis in Sorsogon, Philippines.
AB - The clinical epidemiology of pulmonary paragonimiasis and tuberculosis was
investigated in a known endemic municipality of Sorsogon, Philippines. Records of
diagnosed tuberculosis patients on treatment and follow up at the local Rural
Health Unit over a two year period from 1993 to 1994 were reviewed to provide an
overview of pulmonary tuberculosis in the area, specifically to describe the
population at risk, the basis for diagnosis and the proportion of case
notification who were sputum negative. Patients from the same group of
individuals as well as undiagnosed tuberculosis patients with productive cough,
fever with chest and/or back pain, or hemoptysis were examined to look into
clinical manifestations, duration of symptoms, history of crab-eating and sputum
examination results for acid-fast bacilli and Paragonimus. There was difficulty
in determining the number of non-responders as the records did not have any
provision for the recording of such. Annual tuberculosis case notification rates
for the two years (374 and 401 per 100,000 population) were higher than the
national figure in 1991 (325 per 100,000 population) indicating that tuberculosis
is still a major health problem in the area and tuberculosis control efforts may
have to be more aggressive to better contain the disease. Twenty-six out of 160
individuals surveyed were sputum smear positive for Paragonimus. Paragonimiasis
rates were not significantly different in the two groups (15.6% vs 16.9%,
respectively) indicating that there is a need for routine sputum examination for
Paragonimus which is not available at present. Only six patients surveyed were
sputum smear positive for acid-fast bacilli. A high index of suspicion is
necessary to diagnose paragonimiasis and to be able to differentiate it from
tuberculosis. The diagnosis may be suggested by a patient's place of origin being
a known endemic area, a long period of chronic cough and the habit of eating raw
or insufficiently cooked crabs or crayfish. Laboratories in endemic areas should
have the capacity to differentiate between the two infections by being able to
provide the routine laboratory procedures necessary for definitive diagnosis and
treatment.
PMID- 9656347
TI - Paragonimiasis in Sin Ho District, Lai Chau Province, Viet Nam.
AB - Forty-four cases of pulmonary paragonimiasis, two also with evidence of cerebral
infection, were found in Sin Ho District in Northern Viet Nam. There were 30
males and 14 females, 2-30 years of age. The diagnosis was made by sputum
examination. Pet dogs and wild dogs in the area were also found infected and the
people often eat roasted crabs.
PMID- 9656348
TI - Epidemiology and control of clonorchiasis in Korea.
PMID- 9656349
TI - Epidemiological survey on clonorchiasis sinensis in Yangxin County of Hubei
Province of PR China.
AB - An epidemiological survey of clonorchiasis was conducted at Panqiao township of
Yangxin County of Hubei Province from June to November, 1993. The positive rate
of cercaria in the body of intermediate hosts, Parafossarulus stratulus and
Alocinma longicornis was 12.25% and 3.84% respectively. Positive rates of
metacercariae in the bodies of Pseudonaphona parva was 48.15%, Ctenopharyngodon
idellus 17.24% and Hypophthalmichthys nobilis 18.18%. Positive rate of eggs in
the feces of cats was 36.36% and pigs 16.67%. It has been confirmed that there is
a natural focus of clonorchiasis sinensis at Yangxin County of Hubei Province. A
total population of 6,865 in 20 sites of 10 production brigades of Panqiao
township was surveyed for infection with Clonorchis sinensis. The average
infection rate in the local residents was 5.80%. Male had a higher infection rate
than female. The infected persons were mainly peasants and school girls and boys.
Most of the infected persons had light infections (I0) without a serious clinical
manifestations.
PMID- 9656350
TI - Epidemiological aspects of aquaculture in relation to fish borne trematodiasis in
Malaysia.
AB - Epidemiological studies have been conducted to determine the association between
fish and disease. The fish were obtained from rivers, streams, ponds and lakes
but few from aquaculture farms. While no defined studies have been carried out in
Malaysia, baseline data show that fish obtained from aquaculture farms (mixed
farming) contributed to cases of opisthorchiasis and clonorchiasis.
PMID- 9656351
TI - Fish- and shellfish--borne trematode infections in Canada.
AB - Food-borne trematode infections are endemic in various parts of the world,
particularly Southeast Asia. Despite the high prevalence, morbidity and total
costs of these infections, they remain poorly recognized by public health
authorities and consumers. Factors such as poor sanitation and traditional
methods of food preparation hasten the spread of food-borne trematode infections
in endemic regions and must be carefully examined in order to develop effective
control strategies. There is also a growing risk to consumers in non-endemic
countries as a result of international trade. A considerable quantity of
freshwater fish and shellfish is imported into Canada from endemic countries in
Southeast Asia. Some of these products are imported fresh or processed in such a
way that the infective metacercariae may not be destroyed. Further, current
inspection procedures in Canada may not detect the presence of all parasites in
imported fish products. Therefore, there may be a risk of infection if the fish
or shellfish is consumed raw or lightly cooked. Many of the cases of infection in
Canada involve recent immigrants from endemic regions who have become infected
either before arriving or through the consumption of traditional or ethnic dishes
prepared from imported products. International travel and the increasing
availability and interest in ethnic foods also contribute to the risk of
infection in all Canadians. In addition to these imported trematodes, a number of
species are found in freshwater fishes and shellfish in North America and have
also caused illness in humans. Although the prevalence of infection remains
relatively low in Canada, the need for an increased general awareness of food
borne trematode infections and their causes is indicated.
PMID- 9656352
TI - Application of hazard analysis critical control point (HACCP) as a possible
control measure for Opisthorchis viverrini infection in cultured carp (Puntius
gonionotus).
AB - Opisthorchiasis due to Opisthorchis viverrini and transmitted through infected
freshwater cyprinoid fish (carps) affects more than 8 million people in Thailand,
People's Democratic Republic of Lao, and Vietnam. The Hazard Analysis Critical
Control Point (HACCP)-concept has been recommended by FAO and WHO to be included
in programs to control foodborne trematode infections (FBT). HACCP is a
multifactorial approach to control food hazards through surveillance of diseases,
foods, and operations and education. This study describes the first attempt to
apply HACCP to the prevention and control of Opisthorchis viverrini in pond
culture carp (Puntius gonionotus). The experiment was designed and carried out by
a multidisciplinary "HACCP team" including experts in the field of public health,
parasitology, epidemiology, aquaculture, fisheries extension and fish inspection.
The investigation was performed in two fish ponds in the District of Sun Pa Tong,
Chiang Mai, Thailand. In the experimental pond, fish was cultured according to
HACCP principles and compared with the control pond, which followed conventional
aquaculture practices. Water supply to the pond, fish fry, fish feed and pond
conditions during the growing period were identified as critical control points
(CCPs). Hazards were identified and analyzed, as well as control measures,
critical limits, monitoring procedures, corrective actions, and record keeping
developed for each one of the above CCPs. Complete pond preparation, particularly
aiming to eliminate contamination of pond water with O. viverrini eggs, fish
infected with parasite meacercariae and the first intermediate host (Bithynia
spp), was conducted. After the pond was filled with water, O. viverrini
metacercaria-free fry were released into the pond. The preliminary results
obtained indicate that HACCP-based principles applied to carp pond culture could
be used as a strategy to prevent and control O. viverrini. Further studies should
be undertaken aiming to confirm these preliminary results.
PMID- 9656353
TI - Common culture practices for cyprinids in Asia.
AB - Cyprinids are the largest group of cultured freshwater fish and thus the most
important from the aspect of fish-borne parasitic zoonoses. The common practices
employed in the culture of this group are described to provide background
information which may be used in the formulation of strategies for the control of
these zoonoses. Only the common carp is cultured in monoculture: all the rest of
the carp species are usually cultured in polyculture systems incorporating
several species. Polyculture of cyprinids may be carried out in ponds, cages or
in free range culture in natural or man-made water bodies, Polyculture of
cyprinids is often integrated with agriculture, such as livestock, poultry or
crop farming, utilizing byproducts of the agriculture activity, especially
manure, as a source of nutrient for the fish pond. If precautions are not taken,
this practice may provide an avenue for the transmission of fish borne parasites
to man.
PMID- 9656354
TI - Microbiological status of live eel and processed fish products for export to
Japan.
AB - Live eels and processed fish products from Malaysia are routinely checked for
microbial pathogens before export to Japan. The eels and water from the ponds are
screened for Vibrio cholerae and Salmonella spp, whereas the processed fish
products are tested for microbial contamination (aerobic plate count), coliforms,
E. coil and Vibrio cholerae. Results showed that live eels and water samples were
negative for Vibrio cholerae but Salmonella spp were isolated occasionally.
Various types of processed fish products had counts below 1.0 x 10(5) whilst
coliforms, E. coli and Vibrio cholerae were absent. Records available showed that
procedures involved in the production and transportation of live eel, preparation
and processing of fish products have resulted in relatively safe food products.
PMID- 9656355
TI - Cancer genes and cholangiocarcinoma.
AB - Genes involved in cancer development include oncogenes and tumor suppressor
genes. Ras oncogene and mutations in p53 tumor suppressor gene are commonly found
in many types of cancer. In Thai patients with cholangiocarcinoma ras oncogenes
occur less frequently than in other ethnic groups and furthermore, p53 mutations
also occur with lower incidence when compared with Japanese subjects. It is
unclear at this time the basis for these differences.
PMID- 9656356
TI - Place of surgery in opisthorchiasis associated cholangiocarcinoma.
PMID- 9656357
TI - A brief update on the diagnosis of trichinellosis.
AB - The latest immunological and molecular methods for the diagnosis of swine and
human trichinellosis are briefly reviewed. The following topics are discussed in
more detail: isolation of specific antigens by continuous elution-isoelectric
focusing methods, production of recombinant antigens, nature of immunodominant
antigens, potential use of heat shock proteins (HSPs) as diagnostic antigens,
roles of specific IgE and circulating antigens (CA). The immunodominant antigens
were found to be highly heat resistant. The specificity and sensitivity of
colorimetric sandwich ELISA, microfluorescence (ELFA), enhanced chemiluminescence
(ECIA) and dissociated enhanced lanthanide fluoroimmunoassay (DELFIA) in
detecting CA were compared. The last method is the most sensitive, detecting as
little as 1 ng of antigens/ml of serum. CA was detected as early as 7 days
postinfection of mice. The serum from a patient suspected to have acute
trichinellosis in Hong Kong was also tested positive for CA.
PMID- 9656358
TI - Production specific antigens from Trichinella spiralis using a continuous elution
method and isoelectric focusing.
AB - Immunodominant antigens of 45-53 kDa (one band per fraction) were obtained from
excretory/secretory (E/S) and somatic products of infective-larvae of Trichinella
spiralis using a continuous-elution method. They were further resolved by
isoelectric focusing into different isoforms (45 kDa: pI4.47, 5.09, 5.47 and
5.86; 47 kDa: pI4.72 and 4.97; 53 kDa: pI4.86, 5.11, 5.44 and 5.78). In
immunoblotting, the isoforms of pI 5.09, 5.86, 4.97, 5.44 and 5.78 did not cross
react with antisera against Trichuris suis, Metastrongylus apri, Gnathostoma
hispidum and Stephanurus dentatus. Hence, they have the potential to serve as
specific antigens for the serodiagnosis of trichinellosis.
PMID- 9656359
TI - Serological investigation on human trichinellosis spiralis in Hubei Province of
PR China.
AB - PVC-ELISA for detection of human trichinellosis and its value of field
application was explored during 1988-1994. Sera of 56 cases of clinically
confirmed trichinellosis were tested for serum Trichinella antibodies by way of
PVC-ELISA, and the positive rate was 100%. When the sera of 80 cases of healthy
persons from non-endemic areas were tested for trichinellosis, they were all
negative. For the purpose of exploring the cross-reaction of PVC-ELISA used for
detection of trichinellosis, sera from 144 cases of other parasitoses were
tested. Among them, the sera of 80 cases of schistosomiasis japonica for
trichinellosis were negative; 30 cases of paragonimiasis and 30 cases of
clonorchiasis were also negative. Among sera of 4 cases of cysticercosis, there
was only one positive. The results showed that PVC-ELISA for trichinellosis had a
high sensitivity and specificity. For field application, a population of 800 from
endemic areas were examined by PVC-ELISA, 85 (10.63%) were positive. The infected
persons were mainly in Xiangfan region of Hubei Province. The percentage of the
positive of trichinellosis in Xiangfan region was 64.71% (55/85). The positive
rate of males and females was 13.41% (57/425) and 7.47% (28/375), respectively.
There was a difference among the age groups, with the highest in those > or = 20
years. The findings of this field investigation suggested that the infection rate
of trichinellosis spiralis was high in this province, especially in the Xiangfan
region; and that PVC-ELISA was suitable for field application. The emphasis of
trichinellosis control and research of this province should be in the Xiangfan
region.
PMID- 9656360
TI - Molecular genetic variation in Echinococcus and Taenia: an update.
AB - An update on our understanding of molecular variation in Echinococcus and Taenia
is provided. Genetic variation within certain species of Echinococcus is now a
well accepted phenomenon and a number of intraspecific variants or strains of E.
granulosus, in particular, have been characterized hitherto using a range of
procedures. Newly acquired molecular information has now been used in
epidemiological studies with E. granulosus and in phylogenetic analysis of the
genus Echinococcus. Similarly, DNA approaches have been applied for taxonomic
characterization of the recently recognized Asian Taenia, a third form of human
Taenia, which occurs in Southeast Asia, and which is distinguishable from, but
closely related to, Taenia saginata.
PMID- 9656361
TI - Serodiagnosis of alveolar echinococcosis: detection of antibody against EM18 in
patients and rodents.
AB - An international collaborative study on echinococcosis has been carried out for
the establishment of a simple means for differential serodiagnosis of alveolar
echinococcosis (AE) from other parasitic diseases including cystic echinococcosis
(CE). The main candidate epitope is Em18 (previously undescribed epitope of a low
molecular weight protein of 18.5 kDa). Evaluation of the usefulness of Em18 is
introduced in this review paper. Serum samples showing antibody response against
Em18 are exclusively from AE. The predominant IgG subclass recognizing Em18 is
IgG4 or IgG1 or IgG4 + IgG1 but never IgG2. There are good correlations between
(1) the antibody response against Em18 and the presence of active lesions and (2)
the antibody response against Em18 and the Em2-ELISA values. Em18 is, therefore,
expected to be reasonably reliable and useful for differentiation of active AE
from inactive AE. A new ELISA system using a partially purified Em18 enriched
fraction (PP-Em 18/16-ELISA) has been evaluated for serodiagnosis of AE compared
with Em2plus-ELISA. A total of 194 serum samples were examined: 127 sera from AE
(79) and CE (48) in China where both AE and CE are endemic, 21 sera from CE in
Australia where CE only exists, 28 sera from cysticercosis (21), paragonimiasis
(5) or sparganasis (2) in Korea where no indigenous AE nor CE exists and 11
normal sera. Antibody levels by PP-Em18/16-ELISA were much higher in AE than in
CE and it was also true for commercially available Em2plus-ELISA. Some of CE from
China showed exceptionally higher levels of antibody in comparison with those of
CE from Australia. It is suggested that these strongly positive cases of CE from
China may have been exposed to both species of Echinococcus. Although most of
sera from paragonimiasis showed high antibody levels by Emplus-ELISA, they were
negative by PP-Em18/16-ELISA. Therefore, PP-Em18/16-ELISA is expected to be more
reliable for differentiation of AE from CE and others especially in Asian
countries where paragonimiasis is still not rare. Antibody responses in rodents
naturally infected with E. multilocularis: Serum samples from the wild vole,
Clethrionomys rufocanus bedfordiae, infected with E. multilocularis showed
similar antibody responses as in AE patients, whereas those from Norway rats,
Rattus norvegicus, showed almost none. The latter rodents were simultaneously
infected with Taenia taeniaeformis but showed no antibody response against T.
taeniaeformis either. Therefore, we speculate that Norway rats may only be
infected with E. multilocularis under some immunosuppressed conditions or genetic
unresponsiveness. It is stressed that Em18 is highly specific to E.
multilocularis, and antibody response against Em18 is reasonably reliable for
differentiation of AE from other helminthic infections by Western blot and ELISA
in humans and may be useful for detection of domestic animals contaminated with
E. multilocularis in the endemic area.
PMID- 9656362
TI - A study on the culture medium antigens of Cystcercus cellulosae for detecting
antibodies of cysticercosis by means of ABC-ELISA.
AB - Two antigens of Cysticercus cellulosae, cystic fluid antigen (CFA) and the
culture medium antigen (CMA), were used in Avidin-Biotin Peroxdase Complex-ELISA
(ABC-ELISA) to detect IgG antibodies in 45 cases of cysticercosis treated with
praziquantel. The results revealed the total positive rates as 51.11% with CMA
and 82.22% with CFA. The positive rates in the cases treated within 2 courses of
treatment were 79.17% for CMA and 87.50% for CFA, and only 19.05% for CMA and
71.43% for CFA in the cases treated for more then 3 courses. The fact that the
positive rates decreased as the courses of treatment increased showed that the
sensitivity of CMA might be related to the vital conditions of the worms in the
body, whether alive or dead. It is, therefore, recommended that CMA has the
potential to be employed in ABC-ELISA both as an indicator for diagnosing
cysticercosis and as a reference for the evaluation of the treatment.
PMID- 9656363
TI - Development and characterization of monoclonal antibodies against excretory
secretory antigens of Fasciola gigantica.
AB - Monoclonal antibodies (MAbs) directed against Fasciola gigantica excretory
secretory (ES) antigens were developed from BALB/c mice. Four were selected for
further study, from the panel of hybridomas. The antigen specificities of these
MAbs were characterized and localized by enzyme-linked immunoeletrotransfer blot
(EITB) and immunoperoxidase technique. The target epitopes of these MAbs are 66
kDa protein (MAb 2D10), 66 and 27-26 kDa proteins (MAbs 5D10 and 4F5) and 27-26
kDa protein (MAb 2D9). MAb 2D9 reacted to the antigenic components of the luminal
content and epithelial cell lining the cecum, whereas MAb 2D10 reacted
specifically to the antigens of the tegument and surface membrane. It was found
that all MAbs cross-reacted to various degrees with the antigens extracted from
Schistosoma mansoni, S. mekongi, S. spindale and Paramphistomum spp. However,
when MAbs were diluted to 1:100 or 1:400 significant reduction of their cross
reactivities was observed.
PMID- 9656364
TI - Recent advances in diagnosis of paragonimiasis.
AB - Paragonimiasis in endemic areas can be diagnosed by clinical symptoms. However,
the diagnosis should always be confirmed by microscopic examination of the sputum
or stool in order to find Paragonimus eggs. Within recent years marked advances
in diagnosis of paragonimiasis have been made. Two new approaches comprising a
genetic probe and immunological tests have been developed with claims to be as
good or better than microscopic examinations. This report reviews these two
areas, especially in paragonimiasis caused by Paragonimus heterotremus and P.
westermani. In addition, problem areas in assay development are discussed.
PMID- 9656365
TI - Detection of circulating antigens of Parastrongylus cantonensis in human sera by
sandwich ELISA with specific monoclonal antibody.
AB - A specific monoclonal antibody (AW-3C2) as revealed by ELISA was produced against
the adult worm antigens of Parastrongylus cantonensis and used in a sandwich
ELISA for the detection of circulating antigens in the sera of parastrongyliasis
patients and those with other parasitic diseases. A total of 60 sera was used in
this study. Of these, 10 each were from patients with parastrongyliasis
filariasis, gnathostomiasis, malaria and toxocariasis. The control group
consisted of 53 serum samples from normal healthy Thais and Malaysians. The mean
+/- optical density (OD) values for the normal Thai and Malaysian groups were
0.126 +/- 0.028 and 0.124 +/- 0.029, respectively. Mean OD values of
parastrongyliasis patient group differed significantly from that of the normal
groups as well as those of other parasitic infections. Using a cut-off point of
mean OD +/- 3SD of the normal control groups as indicating a positive reading,
the specificity of the assay with this monoclonal antibody was 100% while the
sensitivity was 50%.
PMID- 9656366
TI - Detection of Angiostrongylus malaysiensis circulating antigen using monoclonal
antibody-based enzyme-linked immunosorbent assay (MAb-ELISA).
AB - Three MAbs 1C4.2D8, 1C4.2C4 and 1C4.1F5 were produced using sonicated adult worm
antigens of Angiostrongylus malaysiensis and they were found to be secreters of
IgG1. The MAbs 1C4.2C4 and 1C4.2D8 were found to react with antigens of A.
malaysiensis and cross-react with the closely related A. cantonensis but not with
other helminths. A total of 108 human sera collected from Orang Asli (aborigenes)
from Grik, in the State of Perak were tested for A. malaysiensis infection using
the MAb-ELISA. MAb 1C4.1F5 and 25 (23%) were positive. Twenty of these positive
samples were tested with the MAb 1C4.2D8 and none was found to be positive.
PMID- 9656367
TI - Vaccine development against Theileria parasite.
AB - Bovine piroplasmosis caused by Theileria sergenti is a major cause of economical
loss in grazing cattle in Japan. We found that parasite stocks and isolates
consist of genetically and antigenically mixed population. To differentiate
parasite populations bearing 2 allelic forms of p32, an immunodominant piroplasm
surface protein, 2 sets of oligonucleotide primers were designed to amplify
either of the 2 alleles by polymerase chain reaction (PCR). By using this allele
specific PCR, we found that the majority of T. sergenti-infected calves in Japan
harbored mixed parasite populations with C and I type parasites. Amino acid
sequence of p32 contains Lys-Glu-Lys (KEK) motif which is one of tripeptide
necessary for malaria parasite to invade erythrocytes. We produced 2 vaccine
candidates, recombinant baculovirus p32 and synthetic peptide containing KEK
motif. Immunization of either recombinant p32 or synthetic peptide containing a
KEK sequence with adjuvant resulted in low parasitemia and reduced the clinical
symptoms compared to control calves. Interestingly, parasites with a p32 allelic
form corresponding to one used as the immunogen were suppressed. Therefore, a
cocktail vaccine containing KEK peptides derived from C and I type parasites is
desired for control Theileria parasite infection in Japan.
PMID- 9656368
TI - Observations on the effects of cysticercosis immune sera on cysticercosis by
scanning electronmicroscopy.
AB - Two antigens of Taenia solium cysticercus, cystic fluid antigen (CFA) and the
culture medium antigen (CMA), were used respectively to immunize rabbits in order
to obtain immunosera. The CMA immunoserum added to culture medium with cysticerci
limited the activities of the bladder worms. By using the scanning
electronmicroscope, we could observe particulate deposits on the surface of the
scolices, suckers and necks of the worms. The CFA immunoserum group showed
similar changes but the deposit was less than that on the worms in the former
group and appeared mainly on the cystic wall. After adding complement to the two
groups mentioned above, we found that the microcilia on the surface of the worms
were swollen and were seriously damaged. The worms treated with praziquantel were
damaged over large area of their surfaces and were affected deep into their
tissues. The damaged parts of the worms were quite different between the two
groups. CMA is secreted by the living worms and therefore the serum antibodies
are more effective than CFA in anti-parasite activity.
PMID- 9656369
TI - Ensuring hygienic quality of food of animal origin by irradiation processing.
PMID- 9656370
TI - Irradiation as a cold pasteurization process of fish and seafood.
PMID- 9656371
TI - Incidence of ascaridoid larvae in Kuwaiti food fishes.
AB - Three hundred and six fish of 83 species were carefully examined in Kuwait during
the period from October 1992 to September 1995 for ascaridoid larvae. Thirty-nine
fishes (12.7%) belonging to 23 species were infected with 9 types of ascaridoid
third-stage larvae: Anisakis simplex, Terranva spp, Contracaecum spp and 6
different types of Hysterothylacium spp (KA-KF). Hysterothylacium larvae
(including all types) were found in all the infected fish except one (94.6%);
Terranova larvae were found in 12 fishes (10 species, 56.1%); Anisakis simplex
larvae occurred in 2 fishes (2 species, 8.6%) and Contracaecum spp larvae in one
fish only.
PMID- 9656372
TI - A survey of bovine, bubaline and swine sarcocystosis in the Philippines.
AB - In a survey conducted from January to December, 1994, muscle tissues in 12 out of
22 slaughtered carabaos ages 8-17 years old and obtained from the Food Terminal
Inc, Abbatoir in Laguna showed numerous white and creamy elliptic-shaped soft
bodied macrocysts in the throat muscles. Microscopic examination of the throat
and cardiac muscle tissues revealed the presence of fusiform-shaped microcysts.
Our observations are consistent with previous reports incriminating Sarcocystis
fusiformis as the most important etiologic agent of bubaline sarcocystosis in the
country. In a survey of bovine sarcocystosis in muscle tissues of imported
Australian cattle (Brahman Breed) and native cattle obtained from various
slaughter houses in Manila and suburbs, prevalence rates of 17% (98/577) and 3%
(1/31) were noted, respectively. Sarcocysts were predominant in skeletal muscles
and to a lesser extent in cardiac, esophageal and diaphragm muscle tissues. Light
microscopic examination of sarcocysts morphology suggests Sarcocystis cruzi (=
Sarcocystis bovis), and Sarcocystis hominis (= Sarcocystis bovihominis) or
Sarcocystis hirsuta (= Sarcocystis bovifelis) as the likely etiologic agents of
bovine sarcocystosis in the country. Of the 225 swines examined, only muscle
tissues from a 6-month old swine revealed very young sarcocysts (= metrocytes). A
review of available documented studies on sarcocystosis suggests that to date,
our findings may represent the first data on the prevalence of bovine and swine
sarcocystosis in the Philippines.
PMID- 9656373
TI - A survey of helminth infection in rats (Rattus spp) from Chiang Mai Moat.
AB - An investigation of helminths in the Norway (brown) rat, Rattus norvegicus, and
roof rat, Rattus rattus, from Chiang Mai Moat during May to August 1995, was
done. Thirty-three out of thirty-eight trapped rats were infected (86.84%); 16 R.
norvegicus (100%) and 17/22 R. rattus (77.27%). The rat was infected with 10
helminth species: 4 trematodes, Centrocestus sp (2.63%), Echinostoma ilocanum
(10.52%), Echinostoma malayanum (10.52%) and Quinqueseralis quinqueseralis
(39.47%); 2 cestodes, Raillietina sp (36.64%) and Taenia sp (cysticercus)
(7.89%); and 4 nematodes, Angiostrongylus cantonensis (42.10%). Nippostrongylus
sp (34.21%), Rictularia sp (52.63%) and egg of Capillaria hepatica (7.89%). The
helminths were found in the small intestine (84.21%), large intestine (42.10%),
lung (36.64%), stomach (28.94%), heart (23.94%), and liver (15.78%). The female
Norway rats were infected with 10 species of helminths and the males with 6
species. In the roof rat, 7 species of helminths were found in females and 6
species in males.
PMID- 9656374
TI - Helminths in house lizards (Reptilia: Gekkonidae).
AB - A survey of helminths in house lizards captured in Amphoe Maung, Chiang Mai
Prouince revealed that the prevalence of helminthic infections in Cosymbotus
platyurus was 94.4% and in Hemidactylus frenatus was 100%. Six species of
helminths were found from C. platyurus: two species of trematodes,
Posterochigenes sp (16.7%), Paradistomoides gregarium (41.1%); one species of
cestode, Oochoristic sp (3.3%); two types of acanthocephalan cystacant, Type I
(4.4%), type II (3.3%); and one species of nematode, Pharyngodon sp (83.3%). The
cystacant Type II was not found in H. frenatus lizard, but the other five worms
were found with higher prevalence. Pharyngodon was the common species in both
lizards with the highest intensity range. So far, these worms have not been
reported in human beings.
PMID- 9656375
TI - Angiostrongylus infections in rats and snails in northeast Thailand.
AB - A survey of Angiostrongylus infections in rats and snails was carried out in the
provinces of Ubon Ratchathani, Udon Thani. Kalasin, Chaiyaphum and Khon Kaen in
northeast Thailand. Only two Rattus norvegicus (3.8%) and one Bandicota indica
(1.4%) out of 151 R. rattus, 52 R. norvegicus and 69 B. indica examined were
infected with adult lung worms. All worms recovered were A. cantonensis.
Prevalence of infection in 423 Pila polita was 0.9% while all of 77 P. ampullacea
were negative for larvae. In contrast to this 36.4% of 500 Achatina fulica
harbored L3 of Angiostrongylus (with variations of between 29% and 46% in the
five provinces). The average infection intensity in A. fulica was 13.6 L3 (1 to
441). Experimental infection of Wistar rats with L3 (isolated from A. fulica
resulted in a recovery rate of 48.3% of adult worms of which 91.7% and 8.3% were
identified as A. cantonensis and A. malaysiensis, respectively. This is the first
proven finding of A. malaysiensis in northeast Thailand.
PMID- 9656376
TI - An outbreak of ascariasis with marked eosinophilia in the southern part of Kyushu
District, Japan, caused by infection with swine ascaris.
AB - Ascariasis has been a representative soil-transmitted intestinal parasitic
disease in warm climates. In Japan, this disease was a major and serious public
health problem only a few decades ago. However, the incidence of the disease
nowadays is reportedly less than 0.01%. Recently in 1994 through 1995, we
experienced a total of 14 cases who were suspected as having ascariasis. They
were characterized by peripheral blood eosinophilia (30-70%), high serum titers
against Ascaris antigen, and most notably, they were absolutely negative for
Ascaris eggs in repeated fecal examinations. Specific antibody titers against
Ascaris antigen correlated well with the degree of eosinophilia. All patients
were living in narrow areas of Kyushu, Japan, where a lot of porcine farms were
located. Most of the patients were asymptomatic and pointed out to have
eosinophilia during follow-up studies of chronic diseases or in regular check-up.
Only one patient had a clear sign of Loffler's syndrome and another had
subcutaneous eosinophilic granuloma. However, laboratory examinations revealed
moderate liver dysfunction in 7 patients and pulmonary infiltrations in 5
patients. Based on circumstantial and serological evidence, these patients were
diagnosed as having been infected with Ascaris lumbricoides suum, a swine
Ascaris.
PMID- 9656377
TI - Newly recognized causative larval nematode (Suborder :Spirurina) of creeping
eruption.
PMID- 9656379
TI - Natural infection of trematodes in Lymnaea (Radix) auricularia rubiginosa in
water reservoirs in Amphoe Muang, Khon Kaen Province.
AB - Lymnaea (Radix) auricularia rubiginosa (Michelin, 1831) was surveyed in 54
reservoirs of 18 districts in Amphoe Muang, Khon Kaen Province during February to
May 1994. Lymnaeid snails were found in the water of 20 reservoirs, of which 16
reservoirs contained clear water and 4 turbid water. Two of the four turbid water
reservoirs received drainage water from Khon Kaen Town. Two thousand four hundred
and eight L. auricularia rubiginosa were collected and examined by shedding and
crushing. Trematode infection occurred in 163 (6.77%) of 2,408 L. auricularia
rubiginosa and some snails were infected with more than one cercarial species.
Ninety-nine snails (4.11%) were infected with echinostomes, while mixed infection
of echinostomes with Fasciola gigantica and with schistosomes was found in 5
snails (0.21%) and 2 snails (0.08%), respectively. Only 1 snail (0.04%), 19
snails (0.79%) and 37 snails (1.54%) were infected with F. gigantica,
schistosomes and unidentified species, respectively. The mean size of infected
snails was 6.89 +/- 2.02 mm (6.20-22.36) while the mean of sampled snails was
13.46 +/- 3.64 mm (4.00-26.55). The water plants which were found in reservoirs
and presented with snails, were creeping water primose (Jusstaea repens), water
lily (Nymphaea sp), water hyacinths (Eichornia crassipes) and grass.
PMID- 9656378
TI - Planorbid snails as potential molluscan intermediate host of a human intestinal
fluke, Neodiplostomum seoulensis (Trematoda : Diplostomatidae) in Korea.
AB - Three species of the pulmonate snails of the family Planorbidae have been
reported from Korea; Gyraulus convexiusculus, Hippeutis (Helicorbis) cantori and
Segmentina (Polypylis) hemisphaerula. Of these 3 species, only H. cantori is
reported as the molluscan intermediate host of Neodiplostomum seoulensis, one of
the important snail-borne human intestinal trematodes in Korea. However, S.
hemisphaerula was also found to be an intermediate host for N. seoulensis. In
field-collected snails, H. cantori and S. hemisphaerula were found shedding
bifurcated cercariae of N. seoulensis, whereas no G. convexiusculus was found
shedding cercariae. In experiments with laboratory-bred snails, only S.
hemisphaerula was susceptible to miracidia of N. seoulensis. Tadpoles of Rana
nigromaculata and R. rugosa were exposed to cercariae shed from field-collected
and laboratory-bred S. hemisphaerula. All tadpoles of R. nigromaculata were found
to be massively infected, but none of the tadpoles of R. rugosa were infected
with larvae of N. seoulensis. Metacercariae from tadpoles of R. nigromaculata and
the snake Rhabdophis tigrinus tigrinus were fed to rats, and eggs of N.
seoulensis were detected in the rat feces one-week later. These rats were killed
and adult N. seoulensis recovered from the small intestines. This is the first
report of S. hemisphaerula as a molluscan intermediate host for N. seoulensis in
Korea.
PMID- 9656380
TI - Light and scanning electron microscopy of Stellantchasmus sp (Trematoda :
Heterophyidae).
AB - Light and scanning electron microscopy of heterophyid fluke, Stellantchasmus sp
were studied. The adults were obtained from Rattus norvegicus, 7 days after
experimental infections with the metacercariae from the body cavity of Dermogenus
pusillus. Living specimens and stained flukes were examined by light microscope.
The present worm differed from S. batillans having a single testis while testes
of S. gallinte were tandam. It is closed to S. falcatus and S. aspinosus but can
not be identified to species because of acetabular spines. The tegumental surface
by SEM was investigated on encysted metacercariae and adults. It was nearly
smooth with one end shallow wide groove of the metacercarial surface. The entire
surface of adult worms were almost covered with scale-like spines, pectinate, 7-9
teeth. The size of scale was largest in the middle of body and decreased both
anterior and posterior. No spines were around the excretory pore but has a
wrinkled surface appearance. The dorsal surface appeared to have scale-like
spines and pectination on the ventral surface. The papillae consisted of a single
club-like cilium, solitary or grouped on the anterior part of the body especially
anterior of oral sucker. Acetabulum located slightly right of the middle and
invagination.
PMID- 9656381
TI - Annual economic loss caused by Taenia saginata asiatica taeniasis in three
endemic areas of east Asia.
AB - The Taenia saginata-like tapeworm in East Asia has been designed as a separate
subspecies of T. saginata. It was named as T. saginata asiatica and the classical
T. saginata as T. saginata saginata. In the course of conducting experimental
infections and morphological studies, a large number of adult worms of T.
saginata asiatica was collected. It is possible to estimate the annual economic
loss caused by this infection, since the worm load and the weight of worm habored
by each infected person were determined from the collection. In the mountainous
areas of Taiwan, the infection rate of T. saginata asiatica taeniasis was 11.0%,
the worm load was 1.6 worms/case, and the average weight of an adult worm was
20.5 g. The annual economic loss was estimated to be US$ 11,327,423. On Cheju
Island of Korea, the infection rate was 6.0%, the worm load was 2 worms/case, and
the average weight of an adult worm was 19.3 g. The annual economic loss was
estimated to be US$ 13,641,021. On Samosir Island of Indonesia, the infection
rate was 21%, the worm load was 1.8 worms/case, and the average weight of an
adult worm was 22 g. The annual economic loss was estimated to be US$ 2,425,500.
These figures indicate that taeniasis is not only a significant public health
problem but also an important economic problem in East Asia.
PMID- 9656382
TI - Metacercariae in fishes of Sun Moon lake which is an endemic area for Clonorchis
sinensis in Taiwan.
AB - The Sun Moon lake in Central Taiwan is a known endemic area for clonorchiasis. Of
the 45 fresh water fish, Hemiculter leucisculus, from the lake that were examined
by artificial gastric juice digestion in October 1995, all were found to harbor
metacercariae in their muscle. The number of metacercariae isolated from each
fish ranged from 2 to 2,185, with an average of 254. A total of 11,443
metacercariae was collected from the 45 fish. Of the 4,223 metacercaria that were
examined under light microscope, 4,064 (96.23%) were found to belong to
Haplorchis taichui, 90(2.13%) to H. pumilio, 2(0.05%) to C. sinensis and 67
(1.59%) to unknown species due to the metacercariae being not yet developed or
immature. The 2 C. sinensis metacercariae were obtained from 2 out of 45 fish
examined. Our results contrast with reports of a decade ago which stated that all
the fish of the Sun Moon lake examined were positive for C. sinensis. Possible
reasons for the decrease of C. sinensis metacercariae are the disappearance of
pig farms around the lake, increased awareness of the trematode by the lakeside
inhabitants and probably the exclusive use of mammals as its definitive host by
C. sinensis. In contrast, besides mammals, Haplorchis spp also use birds as their
definitive hosts.
PMID- 9656383
TI - Metacercariae isolated from cyprinoid fishes in Khon Kaen District by digestion
technic.
AB - Several kinds of fresh-water fishes collected from natural water resources in
Khon Kaen District were digested with 0.25% pepsin A to obtain the infective
stage or metacercariae of fish-borne trematodes. Most of them harbored at least 3
species of trematodes. Two families of medical trematodes, i.e., Family
heterophyidae and Family Opisthorchiidae, were isolated. The heterophyid flukes
consisted of Haplorchis taichui, H. pumilio and Centrocestus formosanus.
Opisthorchis viverrini was the only parasite of the Family Opisthorchiidae found
in these fish. Among these four species, H. taichui was predominant and found in
all kinds of fish examined, especially Hampala dispar.
PMID- 9656384
TI - Playing with fire.
PMID- 9656385
TI - Does hepatitis G virus cause significant clinical liver disease?
AB - Regarding the newly discovered hepatitis G virus (HGV), little is known about its
relation to the cause and clinical significance of acute and chronic liver
disease and hepatocellular carcinoma. Lacking a reliable serum immunoassay, the
only method available for detecting the viral RNA in patients consists of the
rather costly and time consuming RT-PCR. HGV has a worldwide distribution with up
to 5% voluntary and 12.9% commercial blood donors infected, yet it appears to be
asymptomatic. Moreover, HGV is frequently found as a coinfection with HCV or, to
a lesser extent, HBV with symptoms tending to follow the patterns known for HCV
or HBV infection, respectively. Being a blood-borne virus, it is most prevalent
among members of high risk groups, such as IVDUs, patients on hemodialysis,
recipients of blood and blood products and patients infected with HCV, HBV, or
HIV, HGV can be parenterally, vertically, or sexually transmitted and after
prolonged exposure, the virus may be eliminated by the patient's immune response.
As yet, no unambiguous evidence exists regarding HGV's role in causing acute or
chronic liver disease and, apart from a few isolated reports to the contrary, the
infections appear rather mild. Therefore, more studies are required before a
decision can be made whether to routinely screen blood donors for the presence of
HGV RNA.
PMID- 9656386
TI - Hepatitis B and C virus infection prevalence among women in Manila, the
Philippines.
AB - A seroepidemiological survey of HBsAg, HBeAg, anti-HBs, anti-HBc, anti-HBe and
anti-HCV positivities was conducted in 1997 in Manila, The Philippines. Adult
women (21 to 59 years of age) were invited to donate peripheral blood for the
study, and 50 people volunteered. They were nonsmokers, nonhabitual drinkers, and
mostly married; none of them was a professional blood donor. The serum assay
showed that all subjects were negative for HBsAg and HBeAg. Overall, a half (50%)
of the study subjects were positive for any one of the HBV infection markers
(i.e. HBV+). The older group (25 women at 36-59 years of age) showed
significantly higher prevalence than the younger group (25 women at 21-35 years
of age) of positivity to all three HBV antibody markers and therefore HBV
positivity also. None of the study subjects was positive for anti-HCV. Comparison
of the present findings with the results reported in the literature for the 1980s
suggests that the risk of HBV infection and most probably that of HCV infection
also has decreased in this 10-year period in the Philippines.
PMID- 9656387
TI - Maternal and viral factors in vertical transmission of HIV-1 subtype E.
AB - Vertical transmission of HIV-1 is caused by multifactorial factors. To access the
relationship of viral factors involving in perinatal transmission of HIV-1
subtype E, which is the predominant type in Thailand, plasma viral load, blood
CD4+ lymphocyte level, heteroduplex mobility, and V3 sequence of the HIV-1
envelope gene were studied in 32 transmitting and 25 non-transmitting mothers. We
found that HIV-1 subtype E vertical transmission was strongly associated with
high maternal plasma viral RNA (> 4 x 10(4) copies/ml) and high genetic diversity
of envelope gene determined by heteroduplex mobility (< 0.9). The variation of
nucleotide sequences in envelope gene of subtype E vertical transmission could
not determine in V3 region. Hence, plasma viral load and heteroduplex mobility
can be used as prediction factors in vertical transmission of HIV-1 subtype E.
PMID- 9656388
TI - Prevalence of transfusion associated infections in multitransfused children in
relation to mandatory screening of HIV in donated blood.
AB - Any change in risk behavior related to acquisition of human immunodeficiency
virus (HIV) infection is likely to reduce simultaneously the risk for other
agents transmitted through identical routes. A study carried out in the city of
Delhi, India on the load of transfusion associated infections among
multitransfused (MT) children in relation to mandatory screening of HIV infection
in donated blood indicated unchanged prevalence of hepatitis B virus (HBV),
hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among the group of
MT children transfused after the implementation of mandatory screening of HIV
infections in blood banks, i.e. post-implementation period (prevalence of HBV,
HCV and HDV being 32.8%, 31.3% and 1.6% respectively) compared to a group of MT
children transfused over a similar duration before the implementation of
mandatory screening i.e. pre-implementation period (prevalence of HBV, HCV and
HDV being 28.1%, 26.6% and 1.6% respectively). However, reduction could be
recorded in the prevalence of IgM and IgG classes of antibodies to both CMV and
HSV-2 infections among MT children receiving transfusion during the post
implementation period (prevalence of 3.1% and 37.1% for CMV IgM and CMV IgG
respectively; prevalence of 3.1% and 25% for HSV-2 IgM and HSV-2 IgG,
respectively) compared to the group of MT children transfused in the pre
implementation period (prevalence of 15.6% and 56.3% for CMV IgM and CMV IgG
respectively; prevalence of 18.8% and 45.2% for HSV-2 IgM and HSV-2 IgG,
respectively). These reductions were statistically significant (p values < 0.02
and < 0.05 for CMV IgM and CMV IgG; p values < 0.01 and < 0.02 for HSV-2 IgM and
HSV-2 IgG respectively). These observations were in accordance with the recorded
reduction in the prevalence of CMV and HSV-2 infections and unaltered prevalence
of HBV, HCV and HDV infections in the group of donors donating blood during the
post-implementation period compared to those donating in the pre-implementation
period. Study of epidemiological risk factors among blood donors showed a change
in behavior towards safer sex practice with only 13.0% of donors in the post
implementation period having history of sex with one or more female commercial
sex workers during their donation periods compared to 41.5% of donors in the pre
implementation period having similar history (p < 0.001). However no change could
be recorded in the proportion of donors donating at frequency higher than the
permissible guidelines among the two groups. The present study points out
nosocomial transmission as well as limitations in the existing guidelines for
screening of infectious agents in blood banks as possible incriminating factors
towards acquisition of hepatitis virus infections in blood donors as well as in
MT children.
PMID- 9656389
TI - Detection and typing of human papilloma virus DNAs in normal cervix,
intraepithelial neoplasia and cervical cancer in Bangkok.
AB - We detected and typed HPV-DNA by polymerase chain reaction (PCR) in cervico
vaginal lavages of 102 women with normal cervical cytology, 57 patients with
cervical intraepithelial neoplasia (CIN), and 23 cervical cancer patients. HPV
DNA detection and typing by in situ hybridization were also performed in cervical
biopsies from CIN lesions and cancers. Five percent of women with normal cervical
cytology, 46% of CIN, and 61% of cervical cancer were positive for HPV-DNA. Of
CIN cases with positive HPV-DNA, 69, 15, 8, 4 and 4% were HPV-16, -33, -18, -11
and -16/33 respectively. Of cervical cancer cases with positive HPV-DNA, 86% were
HPV-16, 7% were HPV-16/33, 7% were HPV-18/31. HPV typing was performed in
biopsies from 37 CIN and 18 cervical cancers by in situ hybridization. By this
method, 38% of CIN were HPV-DNA positive, of which 71% were HPV-16 and 7% were
each of HPV-11, -18, -31 and -33. Thirty-nine percent of cervical cancers were
positive, of which 71% and 29% were HPV-16 and HPV-16/18 respectively.
PMID- 9656390
TI - The cost of dengue hemorrhagic fever in Thailand.
AB - The economic burden of DHF patients and of the Thai government in providing
treatment and prevention and control of dengue hemorrhagic fever were assessed.
Patient burden was reported by caretakers who stayed with the patients when they
were admitted to three hospitals: Children's Hospital in Bangkok; Suphan Buri
Provincial Hospital and Don Chedi Community Hospital, Don Chedi District in
Suphan Buri Province. The hospital costs--medicine and laboratory costs--were
collected from the treatment forms and the routine service cost was estimated by
the staff of the hospitals. Cost of prevention and control were compiled from the
budget report of Departments of the Ministry of Public Health and the Ministry of
Interior. Based on 184 DHF patients admitted at the three hospitals, the direct
patient costs--treatment cost and the costs of travel, food and lodging--was
66.99 US$ and 61.02 US$ per patient for one episode of DHF in Bangkok and Suphan
Buri, respectively. The total patient costs--direct patient costs and opportunity
costs were 118.29 US$ for a child patient and 161.49 US$ for an adult patient in
Bangkok, 102.82 US$ for a child patient and 138.02 US$ for an adult patient in
Suphan Buri. The net hospital cost in providing treatment for each DHF patient
was 54.6 US$ and 38.65 US$ in Bangkok and Suphan Buri, respectively. The total
cost of prevention and control of DHF in Thailand from government agencies in
1994 was 4.8724 million US$. Based on these findings, the whole expenditure of
Thailand for DHF in 1994, would be at least 12.596 million US$, of which 54.8%
was from the government budget, the rest, 45.2%, was the expenses paid by 51,688
patients and their families. The study concluded that in recording the economic
loss of DHF both the expenditures of the government and also the patient costs-
direct and indirect--should be taken into account.
PMID- 9656391
TI - The effect of nonionic detergent on dengue and Japanese encephalitis virus
antigens in antigen detection ELISA and IgM-capture ELISA.
AB - In order to simplify dengue and Japanese encephalitis (JE) IgM-ELISA, we have
been trying to produce antigens as infected C6/36 cell culture fluid. In this
study, we examined the effect of nonionic detergents, which were used to
inactivate viral infectivity, on dengue and JE antigen titers as well as the
results in an IgM-capture ELISA. In the antigen detection ELISA, antigen titers
were not significantly reduced after treatment with nonionic detergents (Nonidet
P-40 or Triton X-100, at 0.01 to 0.1% final concentration). In contrast, in the
IgM-capture ELISA, the color development was significantly reduced when the
antigens were pretreated with nonionic detergents. The results suggest that
certain epitopes which react with anti-viral IgM antibodies, but not IgG
antibodies, have been destroyed by treatment with nonionic detergents. The
results indicate that we cannot use nonionic detergents to inactivate the
infectivity of assay antigens.
PMID- 9656392
TI - The ICT Malaria Pf: a simple, rapid dipstick test for the diagnosis of Plasmodium
falciparum malaria at the Thai-Myanmar border.
AB - The ICT Malaria Pf test for the detection of Plasmodium falciparum infection was
evaluated in the diagnosis of 305 patients with fever who were admitted to a
hospital located on the Thai-Myanmar border. All patients were admitted for at
least one week to exclude reinfection. The test was performed using admission
blood samples collected into ethylenediaminetetraacetic acid. The sensitivity,
specificity and accuracy of the test were 92.7%, 95.1% and 94.7% respectively,
compared to standard microscopic diagnosis. The ICT Malaria Pf test is an
accurate method for the diagnosis of P. falciparum infection. Its simplicity and
rapidity make it particularly appropriate for use in remote areas where
microscopic examination of blood films is unavailable.
PMID- 9656393
TI - Two doses of artemether/mefloquine or artesunate/mefloquine combination for
multidrug resistant falciparum Malaria.
AB - Plasmodium falciparum in Southeast Asia is highly resistant to chloroquine,
sulfadoxine/ pyrimethamine, quinine and even mefloquine. The use of two doses of
short course artemether/mefloquine combination has been shown to be effective in
a recent study. In the present study, we have assessed the efficacy of short
course treatment with artesunate/mefloquine, in comparison with
artemether/mefloquine in patients with multidrug resistant falciparum malaria.
Ninety-nine Thai male patients who sought consultation at Makham Malaria Clinic,
Chantaburi (eastern part of Thailand), were randomized to receive either the
combination of artemether (150 and 100 mg; group A) or artesunate (150 and 100
mg; group B) with mefloquine (750 and 500 mg) at 24 hours apart. The follow-up
was on days 1, 2, 7, 14, 21, 28, 35 and 42. Patients in both groups showed a
rapid initial response to treatment; fever and parasite were cleared within 48
hours in 100 and 100% vs 91.8 and 96%, for group A vs B, respectively. All
patients in group A had completed the 42 day-follow up; however, two patients in
group B did not finish the 42-day follow-up. The cure rate was 100% in either
group. No serious adverse effects were found. Artemether or artesunate with
mefloquine given two doses at 24 hours apart can be used as effective alternative
treatment regimens for multidrug resistant falciparum malaria.
PMID- 9656394
TI - Pharmacokinetics and ex vivo anti-malarial activity of sera following a single
oral dose of dihydroartemisinin in healthy Thai males.
AB - The pharmacokinetics of dihydroartemisinin (DHA) was studied in eight healthy
male Thai subjects after a single oral dose of 300 mg. Absorption of oral DHA was
rapid, Cmax of 679 (307-1000) ng/ml was observed at 1.5 (1-2.5) hours after
dosing [median (range)]. Plasma concentrations declined monoexponentially and at
12 hours after administration, the levels were below the detection limit (3
ng/ml). A large variation in the AUC (approximately) 50% was observed. The median
(range) AUC was 2010 (636-4079) ng h/ml. The lag time and absorption half-life
(t1/2a) were 0.169 (0.111-0.277) hours and 0.709 (0.367-1.118) hours
respectively. t1/2z was 1.25 (0.79-1.89) hours Vz/f and CL/f were 5.9 (3.5-8.2)
l/kg and 45.3 (28.6-122.8) ml/min/kg, respectively. The pattern of its ex vivo
serum activity coincided with the plasma concentrations of DHA.
PMID- 9656395
TI - Artemether in moderate to severe malaria: a multicenter trial in India.
AB - 154 patients suffering from acute attack of moderate to severe malaria caused by
Plasmodium falciparum were treated with 480 mg artemether, administered
intramuscularly (i.m.) in six equally divided doses at 12 hour intervals. Results
showed a rapid parasite clearance. Mean parasite clearance time (PCT) was found
to be 23.65 +/- 1.57 hours. Mean fever clearance time (FCT) was 35.28 +/- 1.7
hours. Adverse drug events (ADE) were mild and self-limiting. Recrudescence rate
(RR) among the patients followed up was 4.55%. We conclude that artemether is a
safe and effective anti-malarial agent for the treatment of moderate and severe
cases of P. falciparum malaria.
PMID- 9656396
TI - Transplacental passage of Plasmodium falciparum and seroevaluation of newborns in
northern Nigeria.
AB - The findings of a prospective study of 656 near-term pregnant; women, and of the
cord and peripheral blood of newborns of positive mothers are reported. 292
(44.51%) of the pregnant women were infected with Plasmodium falciparum. Further
microscopic screening of the cord blood of newborns of the 292 positive cases at
delivery showed a parasite rate of 10.95%. Transplacental passage of P.
falciparum was confirmed by detection of parasitemia in the peripheral blood of
2.82% of newborns within 7 days of birth. Serological investigation of sera of
284 newborns by indirect fluorescent technic (IFA) with P. falciparum IgM
specific conjugate indicated that 72 (24.66%) had IgM antibodies of P. falciparum
in their blood. The average birthweight of seropositive newborns was 400 g less
than seronegative ones. There was no significant difference in the rate of
neonatal infection regardless of whether or not the mothers had taken chloroquine
prophylaxis.
PMID- 9656397
TI - Plasmodium ovale in Lao PDR.
PMID- 9656398
TI - Immune response against the non-repeat region (293-310) of the circumsporozoite
protein of Plasmodium vivax.
AB - Immunization by peptides based on the repeat sequences of Plasmodium falciparum
or P. vivax antigen(s) have shown inconsistent results during clinical trials in
humans. This could be attributed to the lack of T-cell help or antigenic
polymorphism. Thus, attention has been focused towards the more conserved non
repeat regions. The present study was undertaken to map the antigenic determinant
in the vicinity of region II (outside the repeat) of CS protein of P. vivax. The
immunogenicity of the peptide was studied alone and after linking with
polytuftsin (PT), using alum and Freund's adjuvant, in inbred strains of mice
with different genetic backgrounds. The humoral response and antigen induced T
cell proliferation assays clearly demonstrated the immunomodulatory activity of
PT. Comparable results were observed with antigen(s) administered either in alum
or Freund's adjuvant. The induction of IgG2a and IgG2b antibody isotypes by both,
peptide as well as the conjugate, may indicate that the T-helper response
involved is of Th1 type. Further the immunofluorescence studies have shown that
antibodies recognized the air dried sporozoites of P. cynomolgi. The results thus
show that the above sequence has overlapping B and T-cell determinants and that
alum can be substituted for Freund's adjuvant in generating an effective immune
response.
PMID- 9656399
TI - Granulocyte-macrophage colony-stimulating factor production by T lymphocytes in
Plasmodium berghei-infected mice.
AB - The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by
lymphocytes was examined in murine malaria. When spleen cells or lymph node cells
from P. berghei-infected mice were cultured in vitro with malaria antigen, the GM
CSF production correlated with the incubation time up to 72 hours. When
lymphocytes obtained at various days after infection were cultured with the
antigen, GM-CSF became detectable as early as 2 days after infection, reached a
peak at day 9 and then rapidly decreased. Production of GM-CSF was antigen
specific, and related to the dose of antigen. Treatment of lymphocytes with anti
Thy-1.2 antibody and complement resulted in almost complete loss of GM-CSF
producing activity, while treatment with either anti-CD4 or anti-CD8 antibody and
complement resulted in partial loss of GM-CSF-producing activity, indicating that
both CD4+ and CD8+ T cells are involved in GM-CSF production in malaria. GM-CSF
exhibits glycoprotein nature, and has an apparent molecular weight of 36,000. The
molecular properties of this T-cell derived GM-CSF were compared with those of
known lymphokine GM-CSF.
PMID- 9656400
TI - Immune response profile in patients with active tuberculosis in a BCG vaccinated
area.
AB - Tuberculosis patients with pulmonary (N = 95) or lymph node disease (N = 23) were
assessed for Th1 responses (PPD skin test and lymphocyte blastogenic and
interferon gamma) and Th2 responses (polyclonal and antigen specific IgE). Skin
test responses to PPD and lymphocyte proliferative responses to crude
mycobacterial antigens (PPD, culture filtrate and sonicate) and recall antigens
(tetanus toxoid and streptolysin O) were significantly suppressed (p < 0.001) in
patients with pulmonary disease compared to endemic controls. However, mitogen
(phytohemagglutinin)-stimulated responses were comparable in patients and
controls. Polyclonal and antigen specific (M. tuberculosis culture filtrate) IgE
responses which are considered to be surrogate markers for Th2 responses were
significantly higher in patients with pulmonary disease compared to healthy
endemic controls (Mann Whitney analysis p < 0.01). Patients with lymph node
disease showed strong Th1 responses but did not show significant responses for
either polyclonal or antigen specific IgE. Thus overall suppression of T cell
memory response was observed only in patients with pulmonary disease but not in
patients with lymph node disease suggesting that sequestration of antigen in
different compartments leads to differential activation of Th1 and Th2 responses.
PPD skin test responses were highly positive in endemic controls (47% positive)
and household contacts (86% positive). Furthermore, PPD positivity decreased with
disease severity. Therefore PPD positivity in a BCG vaccinated TB endemic area
cannot be used as a diagnostic marker for active tuberculosis particularly in
advanced disease.
PMID- 9656401
TI - Demographic data on Salmonella enteritidis infection in Thailand, 1990-1995.
AB - The data for the comprehensive analysis of Salmonella enteritidis infection was
based on the information recorded in the request form submitted for Salmonella
typing and the results of serotyping at the WHO National Salmonella and Shigella
Center, Department of Medical Sciences, Ministry of Public Health, Thailand
during 1990-1995. Fifty-one cases of S. enteritidis (SE) infection were confirmed
in 1990. The morbidity being markedly increased each year from 1991 to 1995, with
105, 307, 471, 659 and 877 cases being identified, respectively. Among the
isolates of Salmonella spp, SE was the most common serotype during 1993-1995. The
cases were mostly predominant in Bangkok and then in southern, northeastern,
central and northern regions, respectively. The morbidity rates per 100,000
population per year of SE infection in 1990-1995 were 0.09, 0.18, 0.53, 0.8, 1.11
and 1.47, respectively. Analysis of the infection rate by sex and age
demonstrated that the incidence in males was higher than in females. Adult
patients were more frequently found than adolescent patients. The organism was
found in feces, blood, pus, urine, cerebrospinal fluid and sputum, accounting for
41.7, 35.8, 5.5, 2.5, 1.7 and 0.4%, respectively. The average extraintestinal
isolation index was 0.52.
PMID- 9656402
TI - Specific binding of Burkholderia pseudomallei cells and their cell-surface acid
phosphatase to gangliotetraosylceramide (asialo GM1) and gangliotriaosylceramide
(asialo GM2).
AB - Specific binding between bacterial cells and host tissue is an early step of the
pathogenesis of infection. Burkholderia pseudomallei cells, the causative micro
organisms of melioidosis, were demonstrated to bind specifically to tissue
glycolipids (asialo GM1 and asialo GM2) by solid phase binding assay on thin
layer chromatograms. The detection limit was around 400 pmol of the glycolipids.
Acid phosphatase purified from the culture filtrate of B. pseudomallei was tested
for such binding properties, and the same results were obtained. According to our
previous studies, the enzyme is a glycoprotein located on the cell surface, and
hydrolysed tyrosine phosphate most actively among the substrates so far tested.
The mode of binding between the enzyme and the glycolipids was analyzed by
comparison of binding levels among three samples different in protein content,
sugar content and specific phosphatase activities per protein and sugar residue.
The results suggested the possibility of a receptor-ligand relationship between
the bacterial enzyme and the host-cell glycolipids (asialo GM).
PMID- 9656403
TI - An assessment and evaluation of methods for diagnosis of chlamydial and
gonococcal infections.
AB - Chlamydia trachomatis and Neisseria gonorrhoeae were studied in 350 females and
140 males attending the sexually transmitted disease clinic and AIDS Center, Khon
Kaen zone 6 and the Division of Obstetrics and Gynecology, Khon Kaen Hospital.
Chlamydia trachomatis infection was diagnosed by cell culture (CC), enzyme
immunoassay (EIA) (Bioquest, NSW, Australia) and nucleic acid hybridization
(PACE2 system: Gen-Probe, San Diego, Calif). It was found that the sensitivity,
specificity and positive and negative predictive values in females were 95.7,
100.0, 100.0, 99.7% by the cell culture; 91.3, 99.1, 87.5, 99.4% by the EIA; and
78.3, 99.7, 94.7, 98.5% by the PACE2 respectively. Values of the same parameters
in males were 83.3, 100.0, 100.0, 98.5% by the cell culture; 75.0, 99.2, 90.0,
97.7% by the EIA and 91.7, 100.0, 100.0, 99.2% by PACE2 respectively. The methods
for detection of Neisseria gonorrhoeae infection were conventional culture, PACE2
test and the direct examination (Gram's stain). In females, the sensitivity,
specificity and positive and negative predictive values of the conventional
culture were 85.7, 100.0, 100.0, 99.7% and those of the PACE2 were 85.7, 99.1,
66.7, 99.7% respectively. In males, the values of the same parameters were 81.8,
100.0, 100.0, 100.0% by the conventional culture, 95.5, 100.0, 100.0 and 99.2% by
the PACE2. The prevalence of chlamydial infection in females was 6.6% (23/350)
and that in males was 8.6% (12/140). The prevalence of gonococcal infection in
females was 2.0% (7/350) and in males was 15.7% (22/140). The co-infection of
Chlamydia trachomatis and Neisseria gonorrhoeae in females was 0.9% (3/350) and
no co-infection was found in males. It is concluded that cell culture is an
appropriate method for detection of Chlamydia trachomatis in both genders,
particularly in females. PACE 2 test is the best method for such detection in
symptomatic males while EIA is a good method in females, particularly in
symptomatic females. For gonococcal detection, PACE2 test is a sensitive,
specific and alternative method to the conventional culture. It can be
appropriately applied for the diagnosis of gonococcal infection, particularly in
males.
PMID- 9656404
TI - Retrospective study of empyema cases in National Pediatric Hospital, Cambodia.
AB - Majority of empyema cases admitted into the National Pediatric Hospital (NPH),
Cambodia were of bacterial origin (EB: 95%), the rest were caused by tuberculosis
bacilli (ETB: 5%). The morbidity of overall empyema, empyema of bacterial origin
and empyema of TB origin between boys and girls was the same, even though boys
were more likely to be exposed than girls. The mean age of patients with ETB was
significantly greater than those of EB, 84.7 +/- 46 months versus 52.5 +/- 37
months. Since NPH is located in Phnom Penh, most of our cases were from Kandal,
Phnom Penh, and provinces nearby. On average all of the patients stayed in the
hospital for 23.26 +/- 14.9 days (rank 1-91 days), and the mean duration of
hospitalization of the ETB patients was significantly longer than that of EB
patients, 32 +/- 19 days versus 22 +/- 14 days respectirely. The yearly incidence
of empyema cases in 1990-1993 had the trend of slightly increased frequency
during March to May. The overall EB case fatality rate was 3%, contributed to by
delayed referral of cases.
PMID- 9656405
TI - Ofloxacin containing combined drug regimens in the treatment of multibacillary
leprosy.
AB - The results of ofloxacin containing combined drug regimens in the treatment of 60
multibacillary leprosy cases from January 1989 to June 1995 are reported. The
objective of the trial is to compare the antileprotic property of ofloxacin and
rifampicin in multibacillary leprosy patients and to study the killing rate of M.
leprae by ofloxacin and rifampicin before mass treatment can be recommended. The
complications and side-effects of ofloxacin and rifampicin were of a mild nature
and both drugs were well tolerated. Moderate to marked clinical improvement was
noticed in a short period with ofloxacin containing regimens in multibacillary
leprosy patients. No persisters were detected in any of the 33 specimens (of
mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if
added to the currently used WHO recommended MB-MDT regimen may shorten the
duration of treatment. Ofloxacin, therefore, may be considered as a suitable
alternative in suspected/proven rifampicin resistant cases and where rifampicin
is contraindicated. The results were evaluated on the basis of the clinical
conditions, mycobactericidal effectiveness, signs of drug toxicity and side
effects.
PMID- 9656406
TI - Socio-environmental predictors of soil-transmitted helminthiasis in a rural
community in Malaysia.
AB - Soil-transmitted helminthiasis is a common problem in communities with poor socio
environmental conditions. This study was undertaken to identify important socio
environmental predictors of soil-transmitted helminthiasis in Bachok, a rural
community in Kelantan for the development and implementation of an effective
prevention and control program. Of 363 children randomly sampled, 38.8% were
infected with soil-transmitted helminthiasis. Risk predictors of soil-transmitted
helminthiasis found to be significant after adjustment included poor household
hygiene score and large household size. The probability of being infected was
0.58 amongst children with both of these risk factors.
PMID- 9656407
TI - The impact of primary health care intervention on reinfection of soil-transmitted
helminths in the community.
AB - A study to evaluate the impact of primary healthy (PCH)care practices on the
prevention of reinfection of soil-transmitted helminths (STH) was carried out in
Nakhon Si Thammarat Province, southern Thailand. Fecal samples from the
inhabitants of Ban Paruhas, the implementing village, and Ban Pungsing, the
control village, were examined following mass treatment with a three-day regimen
of albendazole (400 mg). Training of health volunteers, implementation of a
health education program through village broadcasting system and improvements in
sanitation including increasing the number of latrines were carried out at Ban
Paruhas village. After one year of implementation, prevalence and intensity of
STH in both villages were determined using Kato-Katz's method. Pre- and post
intervention stool examination results were compared. The overall prevalence of
STH at post-intervention decreased significantly in both villages, with a greater
degree of reduction appearing in ascariosis and hookworm infections in the
village where PHC was implemented.
PMID- 9656408
TI - Scanning electron microscopic study of microfilaria and the third stage larva of
Wuchereria bancrofti.
AB - The surface structures of microfilaria and of the third stage larva of Wuchereria
bancrofti were studied by scanning electron microscopy. Distinct features were
observed that could be used for differentiating species of this parasite.
Specifically, the sheath of microfilariae of W. bancrofti projected beyond the
head. The head region of the microfilaria was composed of a cephalic cap with
hook, mouth and amphidial opening, and its cuticle showed annulation. Spines were
absent at the first transverse annulation, and the tail end showed a slight
constriction. In the infective stage larva, characters which are used for
differentiating species, such as the two bubble-like ventro-lateral papillae and
one dorso-terminal papilla were rather similar to each other in size, but the
grooves seen around the base were absent. A previously unreported feature of the
third stage larva of W. bancrofti that was discovered in this study is a
papilliform process on the left side of the posterior region, between the anus
and the tail end.
PMID- 9656409
TI - Estimation of ASO titer as an indicator of streptococcal infection precipitating
acute adenolymphangitis in brugian lymphatic filariasis.
AB - Recurrent episodes of acute adenolymphangitis (ADL) are important clinical
manifestations of lymphatic filariasis which contribute significantly to the
progression of lymphedema. It is increasingly being recognized that secondary
bacterial infections play an important role in the etiology of ADL. We examined
the role of streptococcal infection as a precipitating factor of ADL in brugian
filariasis, by determining the anti-streptolysin O (ASO) titers and by isolating
the causative organism wherever possible. The study population consisted of 30
patients with filariasis related ADL (Group A), 30 patients with chronic filarial
edema (Group B) and 60 age and sex matched healthy adults (Group C). ASO titer
was estimated by the latex agglutination method at the time of entry into the
study, at the 15th day and at 3, 6 and 12 months. ASO titers were persistently
elevated in 90% of patients in Group A and a portal of entry for bacterial
infection was detected in all of these patients. In Group B only six patients had
persistently elevated ASO titers. These patients had grade III lymphedema and
three of them had monilial infections in the affected limb. In the control group
none had persistently elevated ASO titers. The elevated ASO titers and the
detection of a site of entry for bacteria in patients with ADL supports a
streptococcal etiology for this condition.
PMID- 9656410
TI - Human infection of Centrocestus caninus in Thailand.
AB - Examination of fecal samples, collected after treatment with praziquantel, of the
persons positive with opisthorchioid eggs residing in the northern provinces of
Thailand, was carried out. Five adults Centrocestus were recovered in one sample
from Doi Saket, Chiang Mai and one adult was found in another fecal sample from
Wiang Pa Pao, Chiang Rai. The worms had 26-30 spines arranging in two rows around
the oral sucker which agreed with the character of C. caninus. This is the first
record of natural human infection with Centrocestus in Thailand.
PMID- 9656411
TI - Visceral leishmaniasis with cutaneous ulcer or cutaneous leishmaniasis in Nepal.
PMID- 9656412
TI - Features of Schistosoma mansoni infection in SCID mice.
AB - Features of Schistosoma mansoni infection in SCID mice, which lack functional T-
and B-lymphocytes, were investigated. The retarded development of parasites as
well as reduction of liver egg recovery in SCID mice was significantly lower than
those in congenic counterpart C.B-17 mice. Furthermore, the rate of parasite
recovery from SCID mice with primary infection was always lower than that from
C.B-17 mice by 20%, showing the innate resistance to S. mansoni infection. SCID
mice vaccinated with UV-attenuated S. mansoni cercariae did not show protective
immunity against a homologous challenge infection. The present innate resistance
exhibited in SCID mice is discussed in relation to cell mediated immunity of
macrophage activation by IFN-gamma which would not involve T-lymphocytes but is
initiated by IL-12 and TNF-alpha cytokines. SCID mice may provide novel
information on the host-parasite relationship in schistosome infections.
PMID- 9656413
TI - Breeding habitats of Aedes aegypti (L) and Aedes. albopictus (Skuse) in villages
of Barru, South Sulawesi, Indonesia.
AB - The breeding habitats of the dengue vector, Aedes aegypti and Aedes albopictus,
were studied using larval collection method inside and outside houses in 6
villages of Barru, South Sulawesi, Indonesia from July 1994 to August 1995. Aedes
aegypti was the dominant species, being abundant indoors especially in the
coastal areas. Aedes albopictus was breeding primarily in outdoor containers in
the hill and mountain areas. Earthen jar was the most common breeding habitat of
Aedes aegypti in all villages surveyed. Drum can was the most common outdoor
breeding habitat of Aedes albopictus in the hill and mountain areas. The high
Breteau indices of Aedes aegypti and Aedes albopictus suggests that these species
may play an important role in the transmission of dengue hemorrhagic fever in
Barru where epidemics of the fever occur occasionally.
PMID- 9656414
TI - A field trial with etofenprox (OMS 3002) as a residual insecticide against
malaria vectors, in Tanjung Bunga district, east Flores, Indonesia.
AB - An operational trial of Vectron (Etofenprox, OMS 3002) was conducted in East
Flores Regency, Nusa Tenggara Timur Province. The compound (Etofenprox 10EW) was
applied as indoor residual spray and as an impregnation treatment for bednets in
two separate areas. Dosage in both cases was 0.2 g/m2. A third area, designated
as control, was untreated. In bioassay tests, bamboo surfaces gave 100% mortality
for 150-160 days post spray, while wooden surfaces and treated bednets both gave
complete mortality for at least 120 days. Malaria cases monitored by successive
malariometric surveys showed steady declines in positivity rates, particularly in
children.
PMID- 9656415
TI - Laboratory evaluation of the biocontrol potential of Mesocyclops
thermocyclopoides (Copepoda: Cyclopidae) against mosquito larvae.
AB - Biocontrol potential of Mesocyclops thermocyclopoides against first instar larvae
of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus was studied
under laboratory conditions. It was found that M. thermocyclopoides had the
highest predation efficacy against Ae. aegypti followed by An. stephensi and Cx.
quinquefasciatus. There was a significant reduction in the predation efficacy of
M. thermocyclopoides against Cx. quinquefasciatus in the presence of alternate
food (p < 0.01). The cage simulation trial indicated that M. themocyclopoides has
the potential to control Ae. aegypti breeding effectively in a container type of
habitat.
PMID- 9656416
TI - Shelf-life of pre-cooked rice oral rehydration salt packets.
AB - The shelf-life of pre-cooked rice oral rehydration salts (ORS) at the household
level was studied in urban Dhaka. To prepare the packets, cooked rice was dried
and ground to fine powder and the salt ingredients were mixed according to the
World Health Organization formulation. For each half liter packet, 10 g glucose
was replaced by 25 g of instant cooked rice powder. The packets were kept in
different environments for three months among 30 households of varying
socioeconomic status. At monthly intervals, two packets from each family were
collected for laboratory tests. Physical characteristics of ORS such as color and
dispersibility remained the same throughout the three month study period.
However, in the third month flavor changed slightly. The electrolyte
concentration of the prepared solution remained the same at the end of the first,
second and third months. However, progressive but minimal increase in moisture
content of the packets was noted over the allotted time period. This increase in
moisture was less when the mixture was packed in double thin layer polythene bags
as opposed to the single layer bags. In conclusion, the shelf-life of pre-cooked
rice ORS remains stable at least up to three months when stored at the household
level. Therefore, pre-cooked rice ORS can be kept at households for future use in
the event of diarrheal episodes.
PMID- 9656417
TI - Health behavior, perceptions, practices, and decision making: sub-national and
socio-demographic differentials in Bangladesh, 1995.
AB - The study examines health behavior, perceptions, practices, and decision making
using data from the 1995 Health and Demographic Survey conducted by the
Bangladesh Bureau of Statistics. Knowledge about causes of diarrhea and food
contamination were higher than knowledge about causes of nightblindness and worm
infestation but this knowledge is inadequate. The household's economic condition
and the respondent's education were found to be positively associated with
disease knowledge and food contamination; the same is also true for health
behavior and practices. Sub-national variation in disease knowledge and food
contamination exists but did not correspond always with the health behavior and
practices. Decisions regarding treatment of disease were made by the husband and
wife together in two-thirds of the cases, however, it was not uniform across
socio-demographic and sub-national categories.
PMID- 9656418
TI - The relationship between maternal weight gain in pregnancy, hemoglobin level,
stature, antenatal attendance and low birth weight.
AB - Low birth weight (birth weight less 2,500 g) remains a major public health
problem in many communities. Five hundred and twenty-eight (528) consecutive
singleton maternities delivered at the Armed Forces Hospital Tabuk, northwest
Saudi Arabia were studied to identify the relationship between prenatal weight
gain, maternal hemoglobin at delivery, maternal stature, antenatal clinic
attendance and low birth weight (LBW). Of the total number, 9.5% (50/528) babies
were of low birth weight, 56% of which were preterm while 44% were term and small
for gestational age, resembling the pattern observed in developed countries
rather than developing countries. Mothers who delivered LBW babies gained
significantly less weight in the 3rd trimester and last 4 weeks of term pregnancy
when compared with controls who had normal weight babies (NW > or = 2,500 g) who
were delivered in the study period (t = 4.06, p < 0.0001, t = 3.7, p < 0.001).
There was no significant difference in the prenatal weight gain in the second
trimester for the two groups of mothers (p = 0.53). Mothers with LBW babies also
had significantly lower Body Mass Index (BMI) at onset of pregnancy (t = 3.8, p =
0.001) and were shorter in height (t = 2.12, p < 0.03). Mothers who delivered
preterm LBW babies had significantly lower hemoglobin levels at delivery when
compared with those who had NW deliveries (p < 0.002). There was no difference in
hemoglobin levels of mothers who had LBW babies at term and those with NW at term
(p = 0.72). For this community, it is suggested that to reduce the LBW baby rate
and improve birth weight, anemia must be prevented in pregnancy; attention needs
to be paid to weight gained in the third trimester and the last 4 weeks of
pregnancy encouraging antenatal clinic attendance, and improving the nutritional
status of female children so that optimal height is achieved by the age of
reproduction.
PMID- 9656419
TI - Zinc and copper status of thalassemic children.
AB - We investigated the amount of both zinc and copper in plasma, erythrocytes and
hair in 11 patients with hemoglobin H disease, 59 patients with beta
thalassemia/HbE disease and 20 patients with homozygous beta-thalassemia. Plasma
and hair zinc levels were found to be much lower, but erythrocyte zinc levels
were higher, in thalassemic patients than in controls. The levels of copper in
both plasma and erythrocytes were higher in the patients than in the controls.
The mechanism with respect to the increase of the amount of both zinc and copper
in erythrocytes was not clear; this result may reflect the impairment of zinc and
copper utilization in tissues in the pathogenesis of these thalassemic patients.
PMID- 9656420
TI - Risk factors for traffic accidents in Bangkok Metropolis: a case-reference study.
AB - It was aimed to study injures from road traffic accidents in Bangkok Metropolis
and identify patients' characteristics as well as to search for risk factors for
traffic accidents leading to hospitalization. The study included 346 in-patient
cases suffering injuries from road traffic accidents in Bangkok Metropolis. The
patients were recruited during a period of 4 months of the year 1992 from five
hospitals in various areas of Bangkok which were judged to be representative for
Bangkok Metropolis. Using the method of case-reference, relative risk could be
estimated for various exposure factors. Most of the patients drove a motorcycle,
had their license for only a short period, and drove more than 5 hours a day.
About one third of the patients were under the influence of alcohol. The traffic
accident characteristics were that they occurred mainly at night time with the
peak between 21.00 and 24.00 hours. About 90% of all traffic accidents occurred
during the rainy season and most of them occurred near to road junctions.
Reference data was available for some variables and the following risk group
could be identified: RR (male-age 20-24) = 17.06 (8.8-33.9), RR (single-marital
status) = 2.25 (1.7-3.1), RR (primary-education) = 6.2 (2.9-12.6), RR (unskilled
labourer-occupation) = 3.91 (2.7-5.9), RR (salesperson-occupation) = 3.34 (2.2
5.0).
PMID- 9656421
TI - Immunologic function in horses after non-specific immunostimulant administration.
AB - Inactivated Propionibacterium acnes is a biologic response modifier for treatment
of non-specific respiratory disease in horses. The objectives of this
investigation were to determine alterations in phagocytic activity, phenotypic
expression of lymphocyte subpopulations and lymphokine-activated killing cell
response in healthy young horses. Samples were collected on day 0, 7 and 14 of
the investigation. Blood samples were obtained via jugular venipuncture and
pulmonary leukocytes were recovered via bronchoalveolar lavage (BAL).
Commercially available P. acnes (Eqstim) was administered intravenously on days
7, 9 and 11 of the investigation. Fever was observed on days 8 and 10, indicating
immune reaction. Total peripheral blood white cell count was increased (P < 0.05)
on day 14 after P. acnes administration compared to values on days 0 and 7. Total
BAL fluid cell count decreased (P < 0.01) on day 14 compared to values on days 0
and 7, which was characterized by a decrease in total lymphocyte (P < 0.01) and
macrophage (P < 0.01) counts. The proportion of lymphocytes in BAL fluid
decreased (P < 0.005) on day 14 compared to values on days 0 and 7, and the
proportion of macrophages increased (P < 0.005) on day 14 compared to values on
days 0 and 7. P. acnes administration increased the total (P < 0.05) and
proportional (P < 0.05) counts of CD4+ T lymphocytes in peripheral blood.
Bronchoalveolar lavage fluid proportion of CD4+ (P < 0.05), CD5+ (P < 0.001) and
MHC II (P < 0.05) lymphocytes increased on day 14 after P. acnes administration
compared to values on days 0 and 7. Nonopsonized phagocytic activity in
peripheral blood increased (P < 0.0005) on day 14 after P. acnes administration
compared to values on days 0 and 7. Lymphokine-activated killing cell activity in
peripheral blood and BAL fluid leukocytes was enhanced (P < 0.005) on day 14
after P. acnes administration compared to values on days 0 and 7. Serum IgG and
IgM concentrations were within laboratory reference values and were not altered
by administration of P. acnes. This investigation demonstrated immunostimulant
and immunomodulatory properties of P. acnes, characterized by increased CD4+ T
lymphocyte expression and LAK activity in peripheral blood and BAL fluid,
increased nonopsonized phagocytosis in peripheral blood leukocytes and decreased
pulmonary cellularity.
PMID- 9656422
TI - Analyses of leucocytes in blood and lymphoid tissues from mink infected with
Aleutian mink disease parvovirus (AMDV).
AB - Mink were infected with Aleutian Mink Disease Parvovirus (AMDV) and sacrificed at
monthly intervals after infection. During this time humoral immune responses and
leucocyte numbers in blood, mesenteric lymph node, spleen and thymus were
monitored. Serum hypergammaglobulinaemia was observed together with elevated
antibody responses to AMDV NS1 and VP1/2 proteins. In blood, a highly significant
increase in CD8+ lymphocytes was observed. However, (presumed)CD4+ cells defined
as CD3+CD8- cells, and B lymphocytes remained relatively constant throughout the
study. The (presumed)CD4+/CD8+ ratio decreased significantly from greater than 2
to less than 0.5 and MHC-II+ blood leucocytes increased significantly during
infection, a large proportion of these being CD8+. Similar changes were observed
in the mesenteric lymph node and spleen. Immunohistology of lymph nodes showed a
massive expansion of the paracortical area due to increased numbers of CD8+
cells. The staining intensity of B lymphocytes in lymph nodes with a CD79a
reactive monoclonal antibody was decreased in the late infection, indicating a
possible greater number of plasma cells. Thymic involution was observed during
the AMDV infection, although relative increases in CD3high (presumed)CD4+ and
CD3highCD8+ single positive cells were observed. These increases were countered
by a corresponding reduction in the CD3low(presumed)CD4+CD8+ double positive cell
population. Immunohistology of the thymus in normal mink showed that most of the
matured CD3+ T cells were present in the inner medulla, while only few CD3+ cells
could be found in the outer cortex. In severely infected mink the thymic
structural organisation vanished, and CD3+ cells were found throughout the organ.
PMID- 9656423
TI - Thymic alterations in feline GM1 gangliosidosis.
AB - GM1 gangliosidosis is an inherited metabolic disease characterized by progressive
neurological deterioration with premature death seen in children and numerous
animals, including cats. We have observed that thymuses from affected cats
greater than seven months of age (GM1 mutant cats) show marked thymic reduction
compared to age-matched normal cats. The studies reported here were done to
describe alterations in the thymus prior to (less then 90 days of age) and during
the development of mild (90 to 210 days of age) to severe (greater than 210 days
of age) progressive neurologic disease and to explore the pathogenesis of the
thymic abnormality. Although histologic examination of the thymus from GM1
affected cats less than 210 days of age showed no significant differences from
age-matched control cats, thymuses from GM1 mutant cats greater than 210 days of
age were significantly reduced in size (approximately 3-fold). Histologic
sections of lymph nodes, adrenal glands, and spleens from GM1 gangliosidosis
affected cats showed no significant differences. Flow cytometric analyses showed
a marked decrease in the percentage of immature CD4+CD8+ thymocytes (p < 0.001)
and significantly increased CD4-CD8+ cells (p < 0.01) in GM1 mutant cats greater
than 210 days of age when compared to normal age matched cats. Co-labelling with
CD4, CD8, and CD5 indicated an increase in the percentage of GM1 mutant cat
thymocytes at this age which were CD5high, suggesting the presence of more mature
cells. Cytometric analyses of subpopulations of peripheral lymphocytes indicated
an increase in CD4-CD8+ cells (p < 0.05) with concurrent decreases in CD4+CD8-
and CD4-CD8- cells (which were not significant). Similar analyses of thymocyte
and lymphocyte subpopulations from cats < 210 days of age showed no significant
differences between GM1 mutant and normal cells. GM1 mutant cats at all ages had
increased surface binding of Cholera toxin B on thymocytes, indicating increased
surface GM1 ganglioside expression. Increases were highly significant in GM1
mutant cats greater than 210 days of age. In situ labelling for apoptosis was
increased in GM1 mutant cats between 90 to 200 days of age when thymic masses
were within normal limits. In GM1 mutant cats over 200 days of age, decreased
labelling was observed when thymic mass was reduced and the CD4+CD8+
subpopulation, known to be very susceptible to apoptosis, was significantly
decreased. These data describe premature thymic involution in feline GM1
gangliosidosis and suggest that increased surface GM1 gangliosides alters
thymocyte development in these cats.
PMID- 9656424
TI - Role of the humoral immune system in Salmonella enteritidis phage type four
infection in chickens.
AB - The role of avian humoral immunity in the clearance of S. enteritidis was
evaluated through bursectomy. After oral inoculation of bursectomized and sham
treated chickens with S. enteritidis, faecal excretion of S. enteritidis was
examined. Organs were collected weekly until six weeks post-inoculation (pi) for
bacteriological enumeration. Antibody isotypes in serum and bile were quantified
by ELISA. Faecal excretion of S. enteritidis was significantly lower in controls
from 13 days pi. Numbers of S. enteritidis in caeca from controls were
significantly decreased from three weeks pi. Numbers of S. enteritidis were
significantly decreased at two weeks pi in the spleen and the liver and at six
weeks pi in the liver. Antibodies to S. enteritidis peaked at two weeks pi in
controls and were absent in bursectomized chickens. These findings indicate that
elimination of S. enteritidis partly depends on humoral immunity. The intestinal
humoral response appeared more effective than the systemic humoral response for
elimination of S. enteritidis.
PMID- 9656425
TI - Isolation of rainbow trout neutrophils with an anti-granulocyte monoclonal
antibody.
AB - A magnetic cell sorting system has been optimised for the purification of rainbow
trout neutrophils using a monoclonal antibody (E3D9) raised against Atlantic
salmon neutrophils. The purified neutrophils have good viability (85%) and purity
(approximately 92%), and were functional in respiratory burst and migration
assays. The isolated neutrophils responded rapidly to PMA stimulation, producing
levels of superoxide anion (4.85 nmols superoxide min-1/10(6) cells)
approximately twice as high as macrophages from the same species. In the
migration assay, there was a four-fold increase in migrating cells using the
purified neutrophils compared with unfractionated blood leucocytes, and a
relatively high neutrophil migratory activity was seen in the absence of serum.
PMID- 9656426
TI - Cloning and sequencing of cDNA encoding bovine macrophage colony-stimulating
factor (bM-CSF) and expression of recombinant bM-CSF using baculovirus.
AB - The cDNAs encoding bovine macrophage colony-stimulating factors alpha and beta (M
CSF alpha and M-CSF beta) were cloned and recombinant bovine M-CSF alpha (rbM-CSF
beta) in its dimeric form was expressed by using a recombinant baculovirus/insect
cell system. The predicted amino acid sequence of rbM-CSF alpha and rbM-CSF beta
shared 83.3 and 75.9% (alpha), 75.3 and 65.9% (beta) similarity with the sequence
for human and murine M-CSFs, respectively. The biological activity of rbM-CSF
beta was confirmed by the colony-forming assay using mouse bone marrow cells. SDS
PAGE under a reducing condition showed that the molecular weight of rbM-CSF beta
was approximately 34 kDa. On the other hand, Western blot analysis under a non
reducing condition revealed that this rbM-CSF beta was secreted in dimeric form
into the cell supernatant.
PMID- 9656427
TI - Analysis of the immunological cross reactivities of 213 well characterized
monoclonal antibodies with specificities against various leucocyte surface
antigens of human and 11 animal species.
AB - 213 Monoclonal antibodies (mAbs) raised against leucocyte surface antigens from
human and 11 animal species were analyzed for reactivities against leucocytes
from human and 15 different animal species. We found 77 mAbs (36%) to cross
react. Altogether, 217 cross reactions were registered out of 3195 possible
combinations (7%). Most of the cross reacting mAbs had integrin or MHC class II
specificities. This study defined cross reactions on the following markers: CD1a,
1c, 2, 4, 5, 8, 9, 11a, 11b, 14, 18, 20, 21, 23, 29, 31, 41, 43, 44, 45, 45R, 46,
49, 61, 62L, TCR gamma/delta, BCR, Thy-1, MHC class I and MHC class II, Swine-WC7
and Cattle-WC1. In order to characterize the molecular weight (MW) of the
corresponding cross reacting antigens, selected mAbs were used to
immunoprecipitate the antigens. The MW's of the analyzed precipitated antigens
were in good agreement with the MWs of the homologous antigens. The followed
strategy was found to be efficient and economical in defining new leucocyte
antigen reactive mAbs.
PMID- 9656428
TI - Characterization of two dog IgE-specific antibodies elicited by different
recombinant fragments of the epsilon chain in hens.
AB - Two recombinant [His]6-tagged fragments of the canine immunoglobulin E (IgE)
heavy chain (second domain: IgEf2 and third and fourth domains: IgEf3/4) were
cloned, expressed in Escherichia coli (E. coli) as [His]6-tagged proteins, and
affinity-purified over nickel-nitrilotriacetic acid columns. The recombinant
proteins were used to immunize hens. The raised and affinity-purified chicken
antibodies (Ab) isolated from egg yolk exhibited specific binding to the
respective recombinant canine IgE fragment (IgEf) on immunoblots and displayed
high titers against the IgEf in ELISA. Immunoblotting of canine serum separated
by PAGE under native conditions with the IgEf2- and IgEf3/4-specific Ab resulted
in staining of a protein of approximately 180 kilodaltons (kD). The IgEf3/4
specific Ab further recognized an 80 kD protein in IgEf3/4-specific Ab affinity
enriched dog serum separated under denaturing conditions. In an ELISA for the
detection of antigen-specific IgE in dog serum, reduced binding of the IgEf
specific Ab was observed after heat treatment of the dog serum. The reactivity of
both of the raised chicken Ab was only present in postimmune reagents and could
only be inhibited by preincubation with the IgEf used for immunization and not
with dog immunoglobulin G, E. coli extract, or with a nonrelevant recombinant
[His]6-tagged protein. In immunohistochemistry, the IgEf3/4-specific Ab
specifically recognized cells in paraffin-embedded tissue sections of lymph
nodes. Furthermore, both of the IgEf-specific Ab elicited positive immediate type
1 skin reactions in dogs. Semiquantitative assessment of total serum IgE in dogs
was developed using IgEf2-specific Ab as coating reagent and the biotinylated
IgEf3/4-specific Ab as developing Ab in ELISA. In conclusion, both IgEf-specific
Ab recognize native dog IgE with the advantages that they are directed against
different and known constant domains of the IgE molecule, and that they can be
used for immunohistochemistry on paraffin-embedded tissue. The two dog IgE
specific Ab could initiate clinical research on the involvement of immediate-type
hypersensitivity reactions in dogs.
PMID- 9656429
TI - Apoptotic fraction in lymphoid tissue of FIV-infected SPF cats.
AB - In the present study the apoptotic fraction has been investigated in peripheral
blood mononuclear cells (PBMCs) and in lymphoid tissue of six clinically
asymptomatic serologically positive specific pathogen free (SPF) FIV-infected
cats with a decline in peripheral blood CD4+ lymphocytes, compared to five FIV-
SPF controls. Apoptosis in PBMCs was scored in relation to cell cycle phases
judged by the integrating cytometric measure of DNA content with 3H-thymidine and
3H-leucine incorporation. Apoptosis in lymphoid tissue was revealed with the
ApopTag-peroxidase kit, quantified by image analysis and expressed as apoptotic
index (number of apoptosis per 100 cells). The high percentage of apoptotic death
in lymphocytes from FIV+ cats was chronologically related to the entrance of
cells in the S phase of the cell cycle (p < 0.0001). No difference in the
apoptotic index was revealed comparing the follicular, cortical + paracortical
and medullary compartments in lymph nodes of FIV+ and FIV- cats. In each group of
cats a similar pattern of apoptosis expression was revealed in lymph nodes:
significantly higher in follicular vs. both cortical + paracortical and medullary
compartments (p < 0.001). In the thymus a significant increase in apoptotic index
was revealed in the cortical compartment of the FIV+ cats compared to FIV- (p <
0.001), while in the spleen both the red and white pulp expressed a higher value
in FIV+ cats compared to FIV-(p < 0.05) and the former showed a pattern of
expression as follows: in the red pulp significantly higher than in the white
pulp (p < 0.001). This investigation suggests that the priming signals for
apoptosis in FIV infection parallels the S phase of the cell cycle and peripheral
blood changes could follow both thymic and splenic modifications in apoptotic
expression.
PMID- 9656430
TI - Modulation of interleukin production by ascorbic acid.
AB - We studied the influence of ascorbate (vitamin C) on peripheral blood mononuclear
cells (PBMC) of pigs with hereditary deficiency in ascorbate synthesis. Groups of
animals were depleted of, or supplemented with dietary ascorbate for up to 5
weeks. B lymphocytes and T lymphocyte subsets differed in the two experimental
groups only marginally and transiently as determined by analysis of cell surface
markers. The proliferative response of PBMC to B and T lymphocyte mitogens was
lower in depleted as compared to supplemented animals. Interleukin (IL)-2 and IL
6 were determined by bioassays and were secreted within few hours after mitogenic
activation of PBMC which contained normal physiological concentrations of
ascorbate. IL-2 production peaked at about 24 h of in vitro culture after Con A
activation, but it lasted for 2-3 days after PWM activation. The production of IL
2 and IL-6 were compared during systemic depletion and supplementation with
ascorbate. Depleted PBMC produced IL-2 which accumulated in cultures instead of
being rapidly consumed by IL-2 dependent cell growth. This suggests that cellular
ascorbate influences the production of IL-2. Secretion of IL-6 by mitogen
activated PBMC was also affected by prolonged dietary ascorbate depletion. The
results suggest that ascorbate levels exert an early effect on immune homeostasis
via reactive oxygen intermediates (ROI)-dependent expression of interleukin
genes, since the transcription factor NF-kappa B is sensitive to ROI and
regulates the expression of interleukin genes.
PMID- 9656431
TI - Influence of the sequence of administration of beta-glucans and a Vibrio damsela
vaccine on the immune response of turbot (Scophthalmus maximus L.).
AB - Yeast (Saccharomyces cerevisae) beta-1,3 glucans were used as adjuvant in a
Vibrio damsela vaccine for turbot (Scophthalmus maximus L.). Turbot were injected
with the adjuvant prior, at the same time and after the vaccine. Several immune
parameters (index and rate of phagocytosis, passive haemolytic plaque numbers,
and agglutinating antibody titers) were determined at different times
postinoculation. The highest activity of all the immune parameters was obtained
when glucans were injected after the bacterin. It is concluded that the sequence
of glucan administration is critical when used as a vaccine adjuvant.
PMID- 9656432
TI - Benzo[a]pyrene-induced hypocellularity of the pronephros in tilapia (Oreochromis
niloticus) is accompanied by alterations in stromal and parenchymal cells and by
enhanced immune cell apoptosis.
AB - Numerous reports indicate that carcinogenic polycyclic aromatic hydrocarbons
(PAH) are mammalian immunotoxicants. These environmental contaminants are widely
distributed in both freshwater and costal marine ecosystems where they have been
found to bioaccumulate in aquatic species, yet limited information exists
regarding potential adverse effects of specific PAH on fish immune function. In
the present report, Oreochromis niloticus fish (tilapia) were exposed by
intraperitoneal injection to 5, 25, or 50 mg/kg of the PAH, benzo[a]pyrene
(B[a]P). Histopathologic evaluation of the primary hematopoietic compartment of
fish, the pronephros, demonstrated increased vacuolation of both stromal and
parenchymal cells, reduction of lymphoid elements, and immune cell apoptosis.
Total pronephros cell counts were diminished in a dose-dependent manner by the
chemical exposure. The oxidative metabolic burst in phorbol myristate acetate
(PMA)-simulated macrophages isolated from the pronephros was significantly
inhibited by B[a]P, but only at the highest dose level employed. The phagocytic
capacity of pronephros macrophages was not altered by the chemical treatment.
PMID- 9656433
TI - Fluorescein isothiocyanate staining and characterization of avian heterophils.
AB - Fluorescein isothiocyanate (FITC) was found to stain cytoplasmic granules of
avian heterophilgranulocytes. In tissue sections, the fluorescent granulocytes
were predominantly distributed adjacent to trabecular bones. The fluorescein
stained granulocytes were abundant in synovial fluids of chickens with synovitis.
A significant correlation was observed in the percent of fluorescein labeled
granulocytes in blood smears and the percent of heterophils determined using an
automated counting method, in unstained blood from normal and Escherichia coli
infected turkeys. The fluorescein-binding heterophils purified from chickens
showed a time dependent increases in the oxidation of 2',7'-dichlorofluorescin
diacetate (DCF-DA) and the reduction of nitroblue tetrazolium (NBT) which were
indicative of changes in oxidative burst in response to phorbol 12-myristate 13
acetate (PMA), Salmonella typhimurium lipopolysaccharide (LPS), and zymosan A
(ZA). These heterophil-activating agents, also, caused significant degranulation
at 16 h post-treatment, as indicated by the loss fluorescence. There were
microscopically visible alterations in the cell shapes and a decrease in the
density of granules due to treatment with LPS, PMA or ZA. In addition, these
cells also showed phagocytic response which was evident at 30 min of incubation
with fluorescent latex particles. Both chicken and turkey heterophils produced
interleukin-6 in vitro at 24 h in response to LPS but not to PMA, FMLP or ZA. The
chicken heterophils showed spontaneous production of matrix metalloproteinases
(MMP) which was significantly enhanced by treatment with LPS, PMA, and ZA;
however, LPS appeared to be most effective in inducing MMP production. These
results demonstrate that the functions of heterophils can be differentially
regulated by different activating agents and the fluorescein binding property of
these cells may be useful for their histochemical identification.
PMID- 9656434
TI - Proceedings of the First International Symposium on Cytokines and the Type I,
Type II Paradigm. Cairns, Australia, Oct. 25-30, 1996.
PMID- 9656435
TI - Comparison of the unique characteristics of the immune system in different
species of mammals.
AB - The current interpretation of how cytokines regulate immune responses is based
largely on studies conducted in humans and rodents. As summarized here,
comparative studies have revealed significant differences in the composition of
the immune system in other species. The difference noted emphasize that it will
not be possible to fully understand the role of cytokines in immune regulation
without comparative studies that include analysis of cytokine function in
additional species.
PMID- 9656436
TI - CD40 ligand-dependent signaling of bovine B lymphocyte development and
differentiation.
AB - The role of IFN-gamma in B cell differentiation in cattle has not been completely
elucidated. We have previously investigated the role of IFN- in the control of
antibody production by bovine B cells using anti-bovine IgM antibody in the solid
phase as a source of costimulation. Using this mimic of a T1-2 antigen, we
demonstrated that IFN-gamma can enhance the production of IgG2 but not IgG1 from
sIgM+ cells. The positive effects of IFN-gamma were enhanced by co-addition to
cultures of rboIL-2. Under these activation conditions, the frequency of cells
expressing mRNA for the IgG2 heavy chain also increased at least two-fold. In
these studies, we investigated the role of IFN-gamma in antibody expression under
T-dependent (TD) activation conditions using mouse fibroblasts transfected with
boCD40L as a surrogate T cell. Under TD conditions, IFN-gamma had less dramatic
effects on the production of IgG2 with IgM predominating in the cultures.
Interestingly, the production of IgA was modestly enhanced with little effect on
the production of IgG1 above baseline levels obtained with medium alone. In
comparison to results with T1-2 conditions of activation, IL-2 did not increase
total amounts of antibody above two-fold. Our results suggest that TH1 cells in
cattle may be limited in their ability to provide B cell help to levels
obtainable in a TH2 cytokine microenvironment due to the effects of IFN-gamma on
bovine B cells co-activated via CD40.
PMID- 9656437
TI - Regulation of bovine interleukin-1 receptors.
AB - Interleukin-1 is a key player in inflammation and the immune response. The
interleukin-1 family consists of three ligands (IL-1 alpha, IL-1 beta, and the IL
1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies
suggest a dynamic relationship among these receptors and ligands that regulates
the magnitude and extent of IL-1 mediated activities. Our laboratory has cloned
and sequenced the bovine type I and II interleukin-1 receptors, and has begun to
investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI
and IL-1RII mRNA levels were upregulated in vitro by various mediators, including
dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNF alpha. Conversely, IL-1RI mRNA
levels were down-regulated by IFN-gamma. An in vivo study indicated that IL-1RII
mRNA levels increased earlier than IL-1RI mRNA levels in dexamethasone-treated
cattle. These findings suggest that early upregulation of IL-1RII, which is a
decoy receptor, may be part of the anti-inflammatory action of glucocorticoids.
Our investigations suggest that anti-inflammatory agents increase expression of
the biologically inactive IL-1RII, as compared with the biologically active IL
1RI, in bovine leukocytes.
PMID- 9656438
TI - Mechanisms of cytokine signal transduction: IL-2, IL-4 and prolactin as
hematopoietin receptor models.
AB - Cytokines, hormones and hematopoietic growth factors transduce biological signals
across the cell membrane via a highly conserved family of single membrane
spanning receptors. The intracellular signal transducing machinery responsible
for mediating these responses has remained largely unknown. However, recent
identification of a homologous class of tyrosine kinases, Janus Kinases (JAKs),
and a related family of transcription factors, signal transducers and activators
of transcription (STATs), has shed new light on the molecular mechanisms
responsible for mediating hematopoietin signaling and immune response. Current
research efforts within the field of cytokine signaling have now shifted to
understanding how these molecules are activated by hematopoietic receptors,
positively and negatively regulated by kinases and phosphatases, and how they
impact on gene transcription to ultimately coordinate cell homeostasis,
proliferation and differentiation. This article will review some of our results
identifying the involvement of JAKs, STATs, and secondary effector molecules
activated following engagement of hematopoietic receptors for IL-2, IL-4, and
prolactin. Here, we provide evidence for the ingenious ability of cytokine
receptors to selectively recruit and activate these proteins among a repertoire
of possible alternative biochemical messengers as a means to affect unique and
general cell responses.
PMID- 9656439
TI - Helper T cell subsets: heterogeneity, functions and development.
AB - The discovery that the nature of cytokine production by CD4+ T lymphocytes could
drastically alter an immune response led to the categorization of distinct helper
T cell subsets, most notably Th1 and Th2. Recent evidence suggests that such
helper responses are actually quite heterogeneous and ultimately, the course of
an immune response depends upon the predominance of particular cytokines. While
the factors leading to the production of individual cytokines are not completely
defined, it is clear that the nature and dose of antigen, location of antigen
challenge, and genetic composition of the individual all play a role in the
process. Elucidating the cellular and molecular pathways responsible for helper T
cell differentiation will ultimately permit the manipulation of immune responses
to pathogens, as well as the development of novel vaccine strategies.
PMID- 9656440
TI - Bovine type 1 and type 2 responses.
AB - The Th1/Th2 paradigm has provided a useful framework for understanding the
observed bias in immune responses that are often dominated by either cell
mediated or humoral responses, and for devising therapeutic strategies to
stimulate T cell- or antibody-mediated immunity. However this paradigm is an
oversimplification of a much more complex immunoregulatory network. Studies with
bovine Th cell clones and immunoregulatory cytokines support this viewpoint. This
paper highlights the progress that has been made in defining type 1 and type 2
responses in cattle. Evidence is presented for the presence of different subtypes
of antigen-specific Th cell clones of cattle which constitute a spectrum of cell
phenotypes, and for cytokine-mediated regulation of Th cell responses that
differs from that observed in mice. The majority of over 60 parasite antigen
specific Th cell clones coexpress IL-4 and IFN-gamma, and polarized cytokine
profiles were rarely observed. Furthermore, IL-2 and IL-10 expression was not
restricted to IFN-gamma or IL-4-producing cells, respectively. This lack of
coordinate regulation of "Th1" and "Th2" cytokines strengthens the emerging
viewpoint that Th1 and Th2 responses, per se, do not typify the immune response
to most pathogens. In addition, we provide evidence that major regulatory
cytokines, IL-4, IL-10, and IL-12, do not selectively exert their negative (IL-4
and IL-10) or positive (IL-12) effects on Th1-like cells.
PMID- 9656442
TI - Influence of IL-12 on interferon-gamma production by bovine leucocyte subsets in
response to bovine respiratory syncytial virus.
AB - The cytokine IL-12 is a key molecule in the regulation of CD4+ T cell development
and specifically potentiates the development of T helper 1 responses in mouse and
man. However the biological effects mediated by bovine IL-12 have not been
defined in cattle. To produce the expression of the two mature proteins a
polyprotein approach was used. This system is employed by positive strand viruses
and encodes both products from a single open reading frame (ORF). The 2A region
of foot-and-mouth disease virus (FMDV) encodes a site that appears to undergo
auto-cleavage. Here the 2A was flanked by sequences encoding the p35 and p40
polypeptides of the heterodimeric cytokine to mediate their cleavage. Formation
of the correct heterodimeric structure is an absolute requirement for IL-12
biologic activity. Using bovine respiratory syncytial virus (BRSV) and ovalbumin
(OVA) we studied the effects of IL-12 on the responses of peripheral blood
mononuclear cells (PBMC) to these antigens, in vitro. The presence of IL-12
markedly influenced the level of IFNg secreted by these cells, and although IL-12
induced IFNg production in the absence of antigenic stimulation, IFNg production
was accelerated and augmented in response to IL-12 and antigen. Analysis of the T
cell subsets by flow cytometry showed that CD4+ T cells comprised the largest
contributors to IFNg production. The WC1 + gd T cells did not appear to
contribute to the production of IFNg.
PMID- 9656441
TI - Interleukin-12 enhances the virus-specific interferon gamma response of pigs to
an inactivated pseudorabies virus vaccine.
AB - Cell-mediated immunity is a major component of the host defense system against
viral infections. Since interleukin (IL)-12 has been shown to be a potent
stimulus for the in vivo generation of interferon-gamma (IFN-gamma)-producing T
cells (i.e. Th-1 cells) in laboratory animals, we evaluated the effect of IL-12
on the cellular immune response of pigs to vaccination against pseudorabies virus
(PrV), a herpesvirus of swine. The magnitude of the cellular immune response was
measured by IFN-gamma ELISPOT analysis of peripheral blood mononuclear cells
(PBMC) from pigs which had been immunized twice, at 2-week intervals, with
either, modified live virus (MLV) alone or with a commercial inactivated PrV
vaccine with or without the coadministration of human recombinant IL-12 (HrIL
12). No significant differences in the titer of virus-neutralizing antibodies or
in the intensity of the virus-specific lymphoproliferative response among the
different treatment groups was observed. However, the number of virus-specific
IFN-gamma-producing cells among PBMC isolated from animals receiving the MLV
vaccine was on average 3.5 times more than animals immunized with the inactivated
vaccine (P = 0.01). Administration of the inactivated vaccine and IL-12 induced a
two-fold higher frequency of virus-specific IFN-gamma-producing cells from that
induced by the inactivated vaccine alone (P < 0.05). Despite this enhancement,
the level of protection from lethal PrV challenge provided by the inactivated
vaccine in combination with IL-12 was the same as that induced by the inactivated
vaccine alone. Both of these vaccination regimes provided significantly lower
levels of protection than those afforded by the MLV vaccine. This study
demonstrates that an inactivated PrV vaccine is a poor inducer of virus-specific
IFN-gamma-producing cells and that this response can be enhanced by
administration of exogenous IL-12. The data provides evidence of a dichotomy in
the humoral and cellular immune responses of pigs to a viral antigen and implies
the existence of a Th-1/Th-2 type regulation of the anti-viral immune response in
pigs.
PMID- 9656443
TI - Measurement of feline cytokine gene expression by quantitative-competitive RT
PCR.
AB - We have developed a method to quantitate feline cytokine gene expression using
competitive RT-PCR. Feline cytokine specific primers were developed that
encompass an intron, thus allowing differentiation of cDNA vs. genomic DNA
amplification products. The PCR products of the primers were verified by
sequencing and Southern blot analysis. For quantitation, a non-homologous RNA
competitor was created for each cytokine of interest. The competitor was designed
to yield an RT-PCR product 10-20% larger than the native sequence, thereby
allowing differentiation of the two products by electrophoresis on an agarose
gel. Both competitor and native sequences used the same primer sequences for RT
(oligo dT) and PCR (cytokine specific). The amplification efficiency of the
competitor and native sequence was shown to be identical which allowed comparison
at any point during the amplification, including the plateau phase. The quantity
of starting cytokine mRNA was determined by interpolation from a standard curve.
As little as 1 microgram of total cellular RNA was required per cytokine
determination. The assay can routinely quantify as few as 1000 copies of template
and spans a range of up to 4 log.
PMID- 9656444
TI - Listeria monocytogenes and Serratia marcescens infections as models for Th1/Th2
immunity in laboratory cats.
AB - Five species of bacteria known to be naturally-occurring pathogens of cats were
screened for their ability to grow in feline macrophages in vitro, and to induce
antibodies and delayed type hypersensitivity (DTH) responses in vivo. Two of
these organisms, L. monocytogenes and S. marcescens, were selected for further
study based on clear-cut differences in their in vitro and in vivo behavior.
Listeria was macrophage tropic, induced DTH, and evoked poor antibody responses
post-recovery, whereas Serratia remained extracellular, did not induce a DTH
reaction, and produced high titer of antibodies. Young specific pathogen free
cats were then inoculated subcutaneously into the drainage areas of the right and
left popliteal and auricular lymph nodes with either L. monocytogenes or S.
marcescens. Each of the four lymph nodes were then removed in sequence over a two
week period, weighed, cultured for viable bacteria, and RNA extracted for Th1/Th2
cytokine mRNA quantitation. Antibody responses and delayed type hypersensitivity
responses were also measured. Identical to pilot studies, cats infected with
Serratia developed very high levels of antibody compared to Listeria infected
cats but no DTH, while Listeria infected cats produced negligible or low titers
of antibodies and strong DTH. Immunity to Listeria occurred around 168 h post
infection as evidenced by the disappearance of living bacteria from the nodes,
while immunity to Serratia took over 264 h. Pronounced lymph node hyperplasia
occurred in both infections, but persisted longer for Serratia. Enlargement of
Serratia infected nodes was associated with marked follicular, primary and
secondary germinal center and medullary hyperplasia. Germinal center formation in
Listeria stimulated nodes was much less intense and dense accumulations of
macrophages dissected between follicles downward from the subcapsular sinuses.
Although functional and histologic studies showed a clear-cut cell-mediated vs.
humoral response in the respective Listeria and Serratia infections, preferential
cytokine mRNA upregulation was observed for only two of the five major Th1/Th2
cytokines measured. Interferon-gamma, a Th1 cytokine, was much more elevated in
the Listeria stimulated nodes, but TNF-alpha (also a Th1 cytokine) was more
elevated in Serratia infected nodes. Interleukin-12, an important Th1 cytokine,
was elevated to equal levels in both infections as were the Th2 cytokines IL-4
and IL-10.
PMID- 9656445
TI - Type 1 and type 2 cytokines in antiviral defense.
AB - Ectromelia virus (EV) is a natural mouse pathogen that causes a generalized
infection termed mousepox, which, in the genetically resistant C57BL/6 (B6)
mouse, is an inapparent disease. In contrast, BALB/c and A strain mice are highly
susceptible; one infectious virus particle can result in 100% mortality. The
contribution of cytokines in the induction of protective immune responses and
recovery from infection with EV in B6, BALB/c and A strain mice have been. In the
spleen and lymph node (LN) of resistant B6 mice, IL-2, IFN-gamma and TNF-alpha
were induced rapidly with large numbers of cells producing these cytokines. All
three cytokines were virtually absent in BALB/c and A strain mice. No significant
differences were found in the numbers of IL-4 producing cells in the spleen or LN
of both resistant and susceptible mice. IFN-gamma-producing cells were detected
in the spleen but not in the lymph node whereas IL-2-producing cells were
detected only in the lymph node of B6 mice. Despite significant increases in the
IFN-gamma mRNA levels in the LN of B6 mice, no protein was detected by
immunocytochemistry. The mRNA levels of IL-2, TNF-alpha and IL-12 were also
rapidly upregulated in LN of B6 mice. The rapid induction of type I cytokines
strongly correlated with a potent antiviral CTL response in B6 mice. The absence
of these cytokines also correlated with a complete absence or delayed induction
of CTL responses to EV in both the BALB/c and A strain mice. IFN-gamma gene knock
out mice on a B6 background were as susceptible to EV as the BALB/c and A strain
mice.
PMID- 9656446
TI - Effect of GM-CSF on HIV-1 replication in monocytes/macrophages in vivo and in
vitro: a review.
AB - Cells of macrophage lineage constitute the main cellular target of Human
Immunodeficiency Virus type 1 (HIV-1). Replication of HIV-1 in
monocyte/macrophages is generally augmented by factors promoting their
differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a
key regular of the differentiation of cells of macrophage lineage. The effects of
GM-CSF on HIV-1 replication in vitro are still controversial. Most of the
published studies suggest that GM-CSF upregulates HIV-1 expression in both
primary cultured macrophages and promonocytic cell lines. There have also been
reports demonstrating that GM-CSF does not affect HIV-1 replication in cells of
macrophage lineage or that GM-CSF can actually suppress HIV-1 expression. In
vivo, GM-CSF administrated to HIV-positive patients at any stage of disease,
without any antiretroviral therapy, appears to increase HIV-1 activity. The
possible mechanism by which GM-CSF might affect HIV-1 replication in macrophages
remains unclear.
PMID- 9656447
TI - Bystander stimulation of T cells in vivo by cytokines.
AB - Immune responses to infectious agents, especially viruses, are often associated
with extensive proliferation of T cells and transient enlargement of the lymphoid
tissues. Since the precursor frequency of T cells for specific antigen is low,
the bulk of the T cells proliferating in the primary response are presumably
stimulated via non-antigen-specific mechanisms, e.g. via cytokines elicited by
the infectious agent concerned. Such 'bystander' stimulation of T cells occurs in
mice injected with agents that elicit production of type I interferon (IFN I).
Induction of IFN I in vivo causes marked stimulation of the CD44hi subset of CD8+
T cells and is prominent after injection of live viruses or products of bacteria
such as lipopolysaccharide. Cytokines elicited by infectious agents may act as
adjuvants during the primary response and could serve to boost the survival of
long-lived memory cells.
PMID- 9656448
TI - Cytokine adjuvants: lessons from the past--guidelines for the future?
AB - Formulation of vaccines has for the most part relied on simple adjuvants which
are able to enhance the immune response to the immunogen. Cytokines are an
attractive alternative to conventional preparations, and have been tested in a
number of different systems. However, experience has indicated that there are a
number of guidelines that must be followed. The dose of cytokine administered is
critical for optimal effect. Too little will have no effect, and too much will
have undesirable side effects. For instance, at high doses IL-2 can induce
autoimmune disease and interferon gamma can have a suppressive effect. Cytokines
may also have to be administered at the same site or even to the same cell as the
antigen for optimal effect. Conjugation or molecular chimerization of antigens
and cytokines can achieve this effect efficiently. Formulation of cytokine with
antigen may overcome any detrimental effect that the antigen may have. Should the
antigen have any suppressive epitopes or have a direct effect on essential
intracellular mechanisms, cytokines may be used to overcome these effects. In
some cases, Th1 or Th2 cytokines have been used to enhance a protective Th1 or
Th2 response. However, the paradigm does not always hold, and Th1 cytokines can
enhance Th2 responses, or have no overall effect on phenotype. Further, in some
host species, there is evidence that there may be no Th1/Th2 dichotomy. The most
important aspect of using cytokines as adjuvants is in ensuring that there is a
balanced response.
PMID- 9656449
TI - Pathogen interactions with cytokines and host defence: an overview.
AB - This review summarises some of the immune evasion tactics adopted by pathogens.
They include the antagonism of immune function through the use of homologues of
cytokine receptors, expression of viral proteins which interact with cytokine
signal transduction and expression of cytokine mimics and host proteins that
influence the Type I or II cytokine responses. Some of the viral defense
molecules that interfere with the functions of cytokines include the EBV protein
BCRF1 (viral IL-10) which blocks synthesis of cytokines such as IFN-gamma, viral
IL-17 and IL-8 receptor encoded by the herpesvirus saimiri genome and chemokine
receptor homologues of Epstein-Barr virus, herpesvirus saimiri and
cytomegalovirus. These immunomodulatory tactics function to protect the host from
the lethal inflammatory effects as well as inhibit the local inflammatory
response elicited to kill the foreign pathogen. Other strategies include the
alterations in cytokine expression such as demonstrated with the hepatitis B
virus (HBV) core protein and terminal protein which can inhibit interferon-beta
gene expression, the interactions of the hepatitis C virus core protein to
lymphotoxin-beta receptor and the effects of the interferon signal transduction
pathway by adenovirus EIA oncogene and HBV by reducing levels or activity of the
cytosolic latent transcriptional factors (STATS). Immune evasive strategies of
helminth parasites related to cytokine activities will also be briefly discussed.
PMID- 9656450
TI - Poxvirus interference with the host cytokine response.
AB - Poxviruses have evolved successfully to survive and replicate in a variety of
species in the presence of an active host immune and inflammatory response. They
manage this, at least in part, by the acquisition and modification of host immune
and inflammatory response modulating genes. A proportion of these virulence genes
encode homologues of host cytokines and cytokine receptors. These include soluble
interferon, IL-1 beta, and TNF-alpha receptor homologues, that block the host
cytokines. Other virulence gene products interfere with interferon signalling
within cells and prevent the cleavage of biologically active IL-1 beta from its
precursor protein. The parapoxvirus orf virus encodes a homologue of ovine IL-10
and a novel GM-CSF-binding protein. By studying poxvirus virulence proteins that
interfere with host cytokine effector responses, important and novel aspects of
the host immune and inflammatory response to infection have been revealed.
PMID- 9656451
TI - Differential migration of Th1 and Th2 cells--implications for vaccine and
infection studies.
AB - Most lymphocytes migrate continuously between the blood and lymphatic system.
This migration does not occur randomly and shows some bias for specific tissue
compartments. In particular, CD4+ memory T cells have been shown to
preferentially migrate to either peripheral or mucosal lymph nodes depending on
their site of origin. The selective migration of lymphocytes into lymph nodes is
facilitated by the differential expression of adhesion molecules on the
lymphocyte surface interacting with their respective ligands on endothelial cells
lining the capillary vessels. The acquisition of these 'mucosal' or 'peripheral'
homing receptors was thought to be dictated by the particular tissue site in
which lymphocyte were activated. A large amount of recent experimentation has
shown that memory T cells generated against infectious agents can have different
functional phenotypes as determined by their cytokine secretion patterns. Two of
these distinct functional phenotypes. Th1 and Th2 cells, are differentially
induced in peripheral and mucosal lymph nodes and recent data has suggested that
the observed tissue-specific migration of memory T cells may be determined by
this functional phenotype rather than the site of activation. Data in support of
this new hypothesis are presented in this paper. In addition, as both the
functional and surface phenotype of lymphocytes is dependent on local hormonal
and cytokine environments, lymphocyte migration patterns may be manipulated by
vaccination and infection.
PMID- 9656452
TI - Antibody and cytokine responses in efferent lymph following vaccination with
different adjuvants.
AB - The cannulated efferent lymph node in sheep was used to examine the effect of
different adjuvants on the antibody and cytokine responses following sub
cutaneous vaccination with a recombinant Taenia ovis antigen (45 W). Vaccination
with Quil A elicited relatively higher levels of IgM than did IFA or Al(OH)3. In
general, 45 W specific IgG1 and IgG2 titres were higher and maintained for longer
periods of time in lymph from sheep vaccinated with IFA and lower and shorter
lived in animals which received the Al(OH)3 based vaccine. Interferon-gamma was
present within one day in efferent lymph from all sheep which received the Quil A
formulation and in only one of the three sheep that received the IFA formulation.
GM-CSF was only detected in lymph from sheep vaccinated with the IFA formulation.
IL-8 was present in lymph prior to vaccination and only animals which received
the Quil A formulation had increased levels of IL-8 after vaccination. Neither of
the inflammatory cytokines IL-1 beta and TNF alpha were detected in efferent
lymph from any animals in this study. This paper highlights the potential of the
lymphatic cannulation model for investigations of the in vivo action of
adjuvants.
PMID- 9656453
TI - Oxidised mannan antigen conjugates preferentially stimulate T1 type immune
responses.
AB - It is desirable to be able to produce either T1 or T2 responses and we have found
that, in mice, mannose--coupled antigens stimulated T2 type responses antibodies
and CTLs, whereas if oxidized, mannose--coupled antigens stimulated T1 responses
little antibody and a potent CTL response. In addition, the cytokine profiles
support the T1rT2 differentiation with these immunizations, in that oxidized
mannan antigen gives IFNg, IL-2 and IL-12 production, whereas in the absence of
oxidization, IL-4 and not the other cytokines is produced. A number of antigens
have been examined--particularly Mucin 1 and the delivery method using mannose
may be applicable to the other antigens.
PMID- 9656454
TI - Potential use of cytokine therapy in poultry.
AB - Newly hatched chickens are highly susceptible to infection during the first 2
weeks of life. The utilisation of cytokines as therapeutic agents in livestock
animals, in particular poultry, has become more feasible with the recent cloning
of cytokine genes and the progression of new technologies such as live vectors.
We have constructed a live recombinant fowlpox virus (FPV) that expresses chicken
myelomonocytic growth factor (fp/cMGF). Administration of fp/cMGF to chicks
resulted in a marked and sustained increase in the number of circulating blood
monocytes as well as an increase in their state of activation, as measured by
enhanced phagocytic activity and elevated production of nitric oxide. We have
recently cloned the gene for chicken interferon-gamma (ChIFN-gamma). Recombinant
ChIFN-gamma was capable of protecting chick fibroblasts from undergoing virus
mediated lysis and induced nitrite secretion from chicken macrophages in vitro.
Preliminary vaccination trials have indicated that co-administration of ChIFN
gamma with antigen (sheep red blood cells) resulted in enhanced secondary (IgG)
antibody responses and allowed a 10-fold lower dose of antigen to be used.
Furthermore, administration of ChIFN-gamma resulted in enhanced weight gain in
chicks and improved their resistance to disease challenge. The ability of
cytokines to combat infection and enhance vaccine efficacy makes them excellent
candidates as a therapeutic agents and adjuvants.
PMID- 9656455
TI - Rapid assessment of antigen induced cytokine expression in memory T cells by flow
cytometry.
AB - Methods for analysis of T cell responses to specific antigen have traditionally
relied on measurements of proliferation or cytokine expression in bulk cultures
of PBMC in long term incubations with putative antigen. These techniques suffer
from the drawback that they do not enable analysis of single cell responses in
the context of unselected cellular backgrounds. It is increasingly important to
not only identify cells on the basis of expression of unique surface antigens but
also to determine functional and molecular parameters of individual cells in
response to a variety of stimuli. We have recently developed methodologies to
rapidly assess T-cell subset responses to polyclonal activators and specific
antigen in whole blood. These procedures determine the percentages of activated
cells and the identification of leucocyte subsets capable of expressing various
cytokines and cell surface antigens. Multiparameter analysis of CD69+ /cytokine +
expression in T cells in response to specific antigen (e.g. CMV, mumps)
demonstrated a range of frequencies from 0.05% to 5.0% within 6 h. Frequencies of
responding T cells were consistent but varied depending upon the antigen. Antigen
specific T cell responses were host specific and both positively and negatively
regulated by antibodies to co-receptors involved in APC-T cell interactions.
These technologies will be discussed in terms of application to problems of
measuring immune function parameters in disease. The modified technique described
in this report is compatible with simple and rapid analysis of clinical samples
and provides a means to directly examine the effects of in vivo drug
concentrations on T cell immunity. Studies are in progress to examine the
sensitivity of this cellular assay to drugs and other therapeutic modalities in
clinical samples.
PMID- 9656456
TI - Increase in CD5+ B cells and depression of immune responses in sheep infected
with Trypanosoma evansi.
AB - The effects of Trypanosoma evansi on the cellular and humoral immune responses of
sheep to Pasteurella haemolytica vaccine were studied. Peripheral blood
lymphocytes (PBLs) from the sheep were analysed using single and double-colour
indirect immunofluorescence staining and flow cytometry to monitor changes in
circulating B and T cell subsets. Serum antibody responses were assayed using the
enzyme-linked immunosorbent assay technique (ELISA), in addition to measuring
local skin reactions at the site of vaccine administration. Results showed
significant increases in circulating B cells in all sheep after the primary (p <
0.01) and secondary (p < 0.001) vaccinations although the increases were much
more dramatic in the T. evansi-infected sheep. In addition, infection induced
significant increases (p < 0.004) both in proportions and numbers of CD5+ B cells
with more than 70% of circulating B cells expressing the CD5 antigen and showed
significant differences (p < 0.01) from those of control sheep in which
vaccination alone failed to induce similar increases. Also, infection resulted in
significant decreases in CD5+ (p < 0.003), CD4+ (p < 0.03) and CD8+ (p < 0.03) T
cell subsets in contrast to their increases in all control animals after
vaccination. Moreover, there were significant suppression of both local skin
reaction (p < 0.005) and serum Ig and IgG1 (p < 0.001) antibody responses to the
vaccine antigen.
PMID- 9656457
TI - Production and characterisation of polyclonal antisera against feline IgE.
AB - Cats, naturally or experimentally infected with Toxocara cati were immunised with
dinitrophenylated ascaris antigen (DNP-Asc). All cats developed immediate skin
reactivity to DNP coupled to bovine serum albumin (DNP-BSA) and the sera of the
nine cats had a heat labile homocytotropic antibody detectable by homologous
Prausnitz-Kustner (PK) tests. Reagin-rich fractions were prepared from these sera
and used for the preparation of polyclonal antisera in rabbits. Resultant
antisera were passed through a immunoabsorbent column of Sepharose 4B coupled to
heated normal cat serum. An immunoabsorbent column prepared with the resultant
antisera removed the PK reactivity from the cat sera, and the activity was
recovered following acid elution. The antiserum failed to detect any recognised
immunoglobulin in cat sera, but precipitated with a heat labile protein with
gamma-1 electrophoretic mobility in the sera of parasited cats. These findings
support the contention that the antisera are specific for feline IgE.
PMID- 9656458
TI - Feline immunoglobulin E: induction of antigen-specific antibody in normal cats
and levels in spontaneously allergic cats.
AB - Sera from 10 cats with symptoms consistent with atopy, from 15 normal household
cats and from 11 laboratory maintained cats were assessed for allergen-specific
IgE and IgG to Dermatophagoides farinae (DF) by enzyme-linked immunosorbent assay
(ELISA). In addition, 10 normal cats were immunised with DF and intradermal skin
tests (IDST) were performed weekly. Sera from the latter were also assessed for
DF-specific IgE by ELISA and using Prausnitz-Kustner (PK) tests. Although DF
specific IgE was detectable in all the atopic cats, there was no significant
difference between the levels in this group and in the clinically normal
household cats. However levels in both these groups were significantly higher
than those in the laboratory maintained cats. Detectable DF-specific IgE was
induced in all of the 10 cats, but the levels were not correlated with the
development of positive IDSTs, nor with the level of IgE as assessed by PK tests.
These findings are consistent with a possible heterogeneity of IgE antibody in
cats.
PMID- 9656459
TI - Adjuvant effects of fluoride on oral immunization of chickens.
AB - The present study was conducted to examine the antibody responses of chickens
after oral immunization and the influence of sodium fluoride (NaF) on their
immunological states. Bovine serum albumin (BSA) was used as an antigen, and the
response was measured by enzyme-linked immunosorbent assays of serum samples,
bile samples, and lachrymal fluids. Oral immunization of chickens with antigen
alone hardly induced antibody responses in sera, bile samples or lachrymal
fluids. Moreover, compared to control chickens, these orally immunized chickens
exhibited a lower serum IgG response to subsequent parenteral immunization,
suggesting that oral immunization induced immunological tolerance in chickens. A
mucosal adjuvant, NaF, could abrogate oral tolerance and elicit an increase in
antibody responses. Chickens, which received oral administration of antigen and
NaF simultaneously, showed a significant rise in serum IgG antibody. Although
there were variations among individual chickens and the titers were low, IgA
antibodies were detected in bile samples and lachrymal fluids.
PMID- 9656460
TI - Early immunopathological events in experimental ovine paratuberculosis.
AB - An experimental oral infection of neonatal (< 2 weeks old) lambs with a cervine
isolate of Mycobacterium avium subspecies paratuberculosis (M.a.
paratuberculosis), the causal agent of ruminant paratuberculosis (Johne's
disease) was used to investigate bacteriological, histopathological and
immunological changes during the early (up to 8 weeks) post-infection phase. In
vitro culture for mycobacteria was positive in one faecal and three mesenteric
lymph node (MLN) samples from the eight infected lambs. All mycobacterial
isolates from MLN were identified as M.a. paratuberculosis by polymerase chain
reaction (PCR). Small-to-medium sized focal granulomata were observed in jejunal
(JPP) and ileal Peyer's patches (IPP) from four of the eight infected lambs.
Compared with controls, JPP from all infected lambs had significantly (p < 0.05)
higher proportions of CD8+ and CD2+ lymphocytes, and there were significantly (p
< 0.05) fewer cells expressing B lymphocyte-associated markers in IPP and MLN.
The T/B cell ratio was significantly (p < 0.05) increased in both JPP and MLN
from infected lambs. The expression of a range of genes for cytokines was
examined using specific reverse transcriptase PCR (RT-PCR) amplification of
messenger RNA (mRNA) template isolated from MLN, JPP and IPP from both groups of
animals. Densitometric analyses indicated that, in infected animals, MLN
expressed significantly (p < 0.05) more mRNA for TNF-alpha: JPP had significantly
increased (p < 0.05) mRNA for GM-CSF and significantly decreased (p < 0.05) mRNA
for IL-4 and IFN-gamma. Infected lambs had significantly (p < 0.05) decreased
titres of both circulating IgG and gut mycobacteria-associated IgG antibody.
Infection was not associated with any consistent changes in lymphocyte reactivity
to specific mycobacterial antigens, IFN-gamma release into supernatants from in
vitro intestinal lymphocyte cultures or gut IgA antibody levels.
PMID- 9656461
TI - Low density blood granulocytic cells induced during classical swine fever are
targets for virus infection.
AB - Classical swine fever virus infection of pigs causes a severe leukopenia and
immunosuppression. In the present study, the kinetics of virus infection, and
identification of target cells for the virus in peripheral blood were analysed.
Virus infection was often not detectable before 5-7 days p.i. A minority of
animals yielded detectable infected cells at 3 days p.i., but < 5% PBMC. It was
not until 10 days p.i. that this figure increased-to 35-70% PBMC depending on the
animal. Detailed analysis of Ficoll-Hypaque-purified PBMC identified the major
population to be SWC3+SWC8+CD14+MHCII- granulocytic cells. Microscopic
observations determined that these low density granulocytic cells in the PBMC
from CSFV infected animals were indeed immature cells. Both the low density
granulocytic cells and monocytes were major targets for CSFV infection in the
peripheral blood. This is the first demonstration that low density granulocytic
cells dominate the blood leukocyte population during CSF, and that such cells are
targets for virus infection. The present work also demonstrates that the
leukocyte population changes, such as B lymphocyte depletion and the relative
dominance of myeloid cells in the blood during CSF, occur before virus infection
of the affected cells. Thus, the pathological mechanism therein is not a direct
consequence of virus infection.
PMID- 9656462
TI - Does Mycobacterium paratuberculosis survive current pasteurization conditions?
PMID- 9656463
TI - Evidence for a genetic variation in the mitochondrial genome affecting traits in
White Leghorn chickens.
AB - A mitochondrial Mspl RFLP which was coselected with Marek's disease (MD)
resistance in White Leghorn chickens was mapped to the NADH subunit IV. The RFLP
was due to a transition, resulting in the change of the low-usage threonine
triplet ACT (Mspl- allele) to the high usage triplet ACC (Mspl+ allele). Trait
association studies within an unselected strain revealed that the Mspl- allele
whose frequency was reduced in MD resistant strains was associated with high body
weight and high egg specific gravity (a measure of eggshell thickness). Analysis
at three different time points indicated a significant interaction between the
mitochondrial genotype and the growth hormone genotype in early but not in late
adulthood. The analysis indicates that mitochondrial variants may contribute to
phenotypic variation in chickens and that such contributions may be dependent on
the genetic background.
PMID- 9656464
TI - Tracking the evolution of the elusive Andean mountain cat (Oreailurus jacobita)
from mitochondrial DNA.
AB - Rarely observed in the wild, the existence of the Andean mountain cat (Oreailurus
jacobita) has been established based on only 3 skulls and 14 museum skins. The
Andean mountain cat's evolutionary relationship to other felids based on
morphological characters is largely contradictory, with evidence aligning it with
South American small spotted cats (ocelot lineage) or alternatively with
pantherine lineage felids. Here we describe the phylogenetic distinctiveness and
placement of the Andean mountain cat using DNA extracted from pieces of nine
independent pelt specimens, including one confiscated from a trapper in 1995. A
phylogenetic analysis of DNA sequences from three rapidly evolving mitochondrial
genes (16S rRNA, NADH-5, and ATP-8) indicate that the Andean mountain cat is a
distinct species belonging to the ocelot lineage. Our findings suggest that the
Andean mountain cat diverged from a common ancestor with the ocelot (Leopardus
paradalis) and margay (L. wiedii) and exhibits moderate levels of genetic
variation.
PMID- 9656465
TI - Heritability estimates of behaviors associated with hunting in dogs.
AB - Heritabilities of traits related to game-bird hunting, measured in the natural
ability test of the North American Versatile Hunting Dog Association (NAVHDA),
were calculated using midparent offspring regressions for five breeds of
continental hunting dogs. Heritabilities of use of nose, search, and waterwork
were moderate (0.25-0.39). Heritability of pointing was high (> 0.40) in one
breed but only moderate in the combined dataset. Desire, cooperation, and
tracking were not significantly correlated between midparent average and
offspring. One of the breeds, large munsterlander, was analyzed for improvement
over the past 15 years. The NAVHDA testing system is used to select breeding
stock in the large munsterlander and improvement in scores was significant.
PMID- 9656466
TI - Distortion of allele frequency distributions provides a test for recent
population bottlenecks.
AB - We use population genetics theory and computer simulations to demonstrate that
population bottlenecks cause a characteristic mode-shift distortion in the
distribution of allele frequencies at selectively neutral loci. Bottlenecks cause
alleles at low frequency (< 0.1) to become less abundant than alleles in one or
more intermediate allele frequency class (e.g., 0.1-0.2). This distortion is
transient and likely to be detectable for only a few dozen generations.
Consequently only recent bottlenecks are likely to be detected by tests for
distortions in distributions of allele frequencies. We illustrate and evaluate a
qualitative graphical method for detecting a bottleneck-induced distortion of
allele frequency distributions. The simple novel method requires no information
on historical population sizes or levels of genetic variation; it requires only
samples of 5 to 20 polymorphic loci and approximately 30 individuals. The
graphical method often differentiates between empirical datasets from
bottlenecked and nonbottlenecked natural populations. Computer simulations show
that the graphical method is likely (P > .80) to detect an allele frequency
distortion after a bottleneck of < or = 20 breeding individuals when 8 to 10
polymorphic microsatellite loci are analyzed.
PMID- 9656467
TI - Juvenile bare: a new hair loss mutation on chromosome 7 of the mouse.
AB - We describe a new juvenile hair loss mutant in the mouse in which the hair
follicle follows irregular pathways to the surface and generally becomes
dystrophic when the mouse is about 23 days of age. Skin from mutant mice older
than 1 month of age is histologically normal, although adult mutant mice show a
slightly more sparse coat than normal. Grafts of mutant littermates skin to SCID
hosts indicate that the condition is probably a systemic response rather than one
of the follicle per se. The hair loss is caused by a recessive mutation, which we
have named juvenile bare (jb), located on proximal chromosome 7.
PMID- 9656468
TI - Shorn (shn): a new mutation causing hypotrichosis in the Norway rat.
AB - We report the identification of an autosomal recessive mutation in the Norway rat
that causes an almost complete absence of normal hair. The mutation, named shorn
(gene symbol shn), is distinct from fuzzy, hairless, and Rowett nude, and is not
closely linked with any of these markers or with albino.
PMID- 9656469
TI - Developmental stability in different genetic stocks of white rock chickens.
AB - Asymmetries were determined for several bilateral traits in females from a line
of chickens selected for 39 generations for low 56 day body weight (LWS) and in a
subline of LWS where selection had been relaxed for four generations (LWR).
Because of reduced food intake under ad libitum feeding, some LWS females do not
commence egg production, a condition that can be overcome by relaxing selection
for a generation or two. Bilateral traits, measured at 240 days of age in LWS non
layers, LWS layers, and LWR layers, were shank length and diameter, distance
between the auditory canal and the posterior junction of the upper and lower
mandible, and weight and length of the first primary wing feather. Other traits
measured were body weights at 56, 168, and 240 days of age and age at first egg.
Fluctuating asymmetry, a good overall measure of developmental stability, was
lower in the relaxed than selected line. Means of relative asymmetries were also
lower for LWR females than LWS layers and nonlayers which were similar.
PMID- 9656470
TI - Chromosome number of Severtzov's sheep (Ovis ammon severtzovi): G-banded
karyotype comparisons within ovis.
AB - Severtzov's sheep (Ovis ammon severtzovi; Nasonov 1914) has a 2n = 56 diploid
chromosome number and a karyotype consisting of two pairs of biarmed and 25 pairs
of acrocentric autosomes, a large acrocentric X, and a minute biarmed Y. The G
banding patterns of the largest pair of biarmed chromosomes were identical to
those of the largest biarmed chromosomes in all wild and domestic sheep of the
genus Ovis. The banding patterns of the second pair of biarmed chromosomes were
identical to the third pair of biarmed chromosomes in all sheep of the genus Ovis
with 2n = 54 and to the third largest pair of chromosomes in the 2n = 52
karyotype of the Siberian snow sheep (O. nivicola). The G-banded karyotype of
Severtzov's sheep is consistent with all subspecies of argali (O. ammon spp.)
that have been karyotyped. Numerical ascription of acrocentric chromosome
equivalents based upon the fundamental karyotype of Ovis that gave rise to the
biarmed chromosomes of severtzovi are 1 and 3, and 5 and 11 for the largest and
second largest biarmed chromosomes, respectively. Based upon diploid chromosome
number and G bands, Severtzov's sheep should be considered a subspecies of argali
and not a urial.
PMID- 9656471
TI - Locations of human genes for alpha 1A, alpha 1B, and alpha 1E calcium channels
determined by radiation hybrid mapping.
AB - To determine more detailed locations of human P/Q-type (alpha 1A), N-type (alpha
1B), and R-type (alpha 1E) calcium channel genes, we have mapped CACNL1A4 (alpha
1A), CACNL1A5 (alpha 1B), and CACNL1A6 (alpha 1E) loci using a radiation hybrid
panel. Locations of these loci are as follows: WI-4669-5.1 cR3000-CACNL1A4-4.1
cR3000-CHLC.GATA27C12 on chromosome 19; D9S158-2.0 cR3000-CACNL1A5-4.3 cR3000-WI
14048 on chromosome 9; D1S215-4.4 cR3000-CACNL1A6-4.5 cR3000-D1S240 on chromosome
1.
PMID- 9656472
TI - Estimation of the proportion of triploids in populations with diploid and
triploid individuals.
AB - Populations with diploid and triploid individuals co-occur in various plant and
animal species, but detecting their relative frequencies is problematic.
Microsatellite markers can be used to detect triploids that have three distinct
alleles at a given locus, but cannot identify triploids that are partially or
fully homozygous (i.e., possessing two or three copies of the same allele).
Detection of partially homozygous triploids is sometimes possible with allozymes
if no dosage compensation occurs. However, the inference of triploidy from uneven
band intensities is not always reliable, making it difficult to estimate the
actual proportion of triploids in a population. We present an iterative
mathematical procedure for estimating the overall proportion of triploids from
allozyme and microsatellite data. This method also estimates corrected allele
frequencies by accounting for potentially hidden cases of homozygosity occurring
in triploid individuals with multiple copies of an allele.
PMID- 9656473
TI - Intrinsic two-dimensional features as textons.
AB - We suggest that intrinsic two-dimensional (i2D) features, computationally defined
as the outputs of nonlinear operators that model the activity of end-stopped
neurons, play a role in preattentive texture discrimination. We first show that
for discriminable textures with identical power spectra the predictions of
traditional models depend on the type of nonlinearity and fail for energy
measures. We then argue that the concept of intrinsic dimensionality, and the
existence of end-stopped neurons, can help us to understand the role of the
nonlinearities. Furthermore, we show examples in which models without strong i2D
selectivity fail to predict the correct ranking order of perceptual segregation.
Our arguments regarding the importance of i2D features resemble the arguments of
Julesz and co-workers regarding textons such as terminators and crossings.
However, we provide a computational framework that identifies textons with the
outputs of nonlinear operators that are selective to i2D features.
PMID- 9656474
TI - Apparent contrast and spatial frequency of local texture elements.
AB - We measured the apparent contrast and spatial frequency of a parafoveal Gabor
signal located at the center of an array of Gabor signals as a function of both
element density and the direction of contrast and spatial frequency of the
surrounding elements. The target Gabor appeared lower in contrast and higher in
spatial frequency when the elements were in close proximity, regardless of the
direction of contrast and spatial frequency of the surrounding elements. Overall,
the evidence suggests that the appearance of a parafoveal target is strongly
affected by its visual context. These findings provide additional support for the
existence of spatial interactions among neurons implicated in textural
processing.
PMID- 9656475
TI - Functional division of the retina and binocular correspondence.
AB - Spatial vision relies on a spatial coding of object directions sensed by the
retinal photoreceptors. An empirically measured constant error in this coding of
perceived space is described classically as a barrel distortion involving long
horizontal lines. A Cartesian retinal coordinate system is constructed to
describe the transformation from object space to perceived space. This system
establishes a subjective horizontal and vertical (isoelevation and isoazimuth)
grid for each eye. The retinal entities that mediate subjective sense of constant
elevation (horizontal) and constant azimuth (vertical) constitute the functional
division of the retina, and they are described by a model with a single parameter
zp, which determines the curvatures of a set of hyperbolic isopters. Empirical
isoelevation positions were measured, which were described by this model. The
best-fitting zp values appeared to be independent of viewing distance, similar
for the two eyes of the same observer but differing significantly among
observers. The functional-retinal-division model and horizontal retinal shear, as
described by Helmholtz, were used to predict the spatial distributions of
binocular corresponding points. The disparity field on a frontoparallel plane at
a finite viewing distance showed marked asymmetry between the upper and the lower
visual fields. The hyperbolic isoelevation and isoazimuth curves dramatically
exaggerated this asymmetry. This theoretical disparity field provides a guideline
for experiments that attempt to show the effect of binocular disparity in the
periphery.
PMID- 9656476
TI - Color-luminance interaction: data produced by oblique cross masking.
AB - Threshold-elevation (TE-) versus-mask-spatial-frequency (SF) curves and TE-versus
mask-contrast curves, produced by the oblique-masking technique, were reported
for uncrossed stimuli (color-test-on-color-mask and luminance-test-on-luminance
mask) [Invest. Ophthalmol. Visual Sci. Suppl. 34, 751 (1993) and Vision. Res. 23,
873 (1983)]. The technique minimizes the artifacts that are due to spatial phase
effects, spatial beats, spatial probability summation, and local cues. My goal
was to measure these curves for crossed stimuli (color-test-on-luminance-mask and
luminance-test-on-color-mask) by this oblique-masking technique and to compare
the curves with those reported in previous studies. For this purpose threshold
contrasts were measured by a yes-no procedure with randomized double staircases.
Test targets were vertical spatially localized (D6) patterns, and masks were
oblique sinusoidal patterns; both the test and the mask were presented
simultaneously, for 2 s (Gaussian window), on a color monitor interfaced with an
ATVista system and a Powell achromatizing lens. The test SF's were 0.125, 0.5, 2,
4, and 8 cycles per degree (cpd); mask SF's were 0.031-16 cpd; and mask contrasts
were 6.25%-50%. Furthermore, the Red-Green channel was defined by the minimum
flicker and the hue cancellation techniques. Results show mostly masking effect
(TE > 1) at contrasts above threshold; sometimes, separability (TE = 1) and above
threshold facilitation (TE < 1) effects were also observed, depending on the test
SF, the mask SF, the mask contrast, and the subject. In general, the magnitudes
of TE's are smaller and the TE-versus-mask-SF curves are slightly narrower for
the oblique-cross-masking conditions than those for the respective oblique
uncross masking. In addition, the TE-versus-mask-contrast curves for the crossed
conditions are mostly shallower than those for the respective uncrossed
conditions. Furthermore, mostly the color-luminance asymmetry (color masks
luminance more than luminance masks color) is found, in mild form, for SF's > or
= 0.5 cpd. For the lower SF of 0.125 cpd, there is either a lack of asymmetry or
a very mild asymmetry of the opposite kind (luminance masks color slightly more
than color masks luminance) seems to prevail. In general, the oblique-masking
data shows mild asymmetry and reduced facilitation; both are consistent with
reduced local cues, similar to those shown by randomized phase data, thus making
the data suitable for SF analysis; moreover, at high contrast, the masking data
are consistent with those reported in previous studies.
PMID- 9656477
TI - Identification of illuminant and object colors: heuristic-based algorithms.
AB - In everyday scenes, from perceived colors of objects and terrains, observers can
simultaneously identify objects across illuminants and identify the nature of the
light, e.g., as sunlight or cloudy. As a formal problem, identifying objects and
illuminants from the color information provided by sensor responses is
underdetermined. It is shown how the problem can be simplified considerably by
the empirical result that chromaticities of sets of objects under one illuminant
are approximately affine transformations of the chromaticities under spectrally
different illuminants. Algorithms that use the affine nature of the correlation
as a heuristic can identify objects of identical spectral reflectance across
scenes lit simultaneously or successively by different illuminants. The relative
chromaticities of the illuminants are estimated as part of the computation.
Because information about objects and illuminants is useful in many different
tasks, it would be more advantageous for the visual system to use such algorithms
to extract both sorts of information from retinal signals than to discount either
automatically at an early neural stage.
PMID- 9656478
TI - Range estimation by optical differentiation.
AB - We describe a novel formulation of the range recovery problem based on
computation of the differential variation in image intensities with respect to
changes in camera position. This method uses a single stationary camera and a
pair of calibrated optical masks to measure this differential quantity directly.
We also describe a variant based on changes in aperture size. The subsequent
computation of the range image involves simple arithmetic operations and is
suitable for real-time implementation. We present the theory of this technique
and show results from a prototype camera that we have constructed.
PMID- 9656479
TI - Measurement of smoothed Wigner phase-space distributions for small-angle
scattering in a turbid medium.
AB - We study Wigner phase-space distributions W (x, p) in position (x) and momentum
(p) for light undergoing multiple small-angle scattering in a turbid medium.
Smoothed Wigner phase-space distributions are measured by using a heterodyne
technique that achieves position and momentum resolution determined by the width
and the diffraction angle of the local oscillator beam. The sample consists of
5.7-micron-radius polystyrene spheres suspended in a water-glycerol mixture. The
momentum distribution of the transmitted light is found to contain a ballistic
peak, a narrow diffractive pedestal, and a broad background. The narrow
diffractive pedestal is found to decay more slowly than the ballistic peak as the
concentration of scatterers is increased. The data are in excellent agreement
with a simple theoretical model that explains the behavior of the narrow pedestal
by including multiple diffractive scattering and treating large-angle scattering
as a loss.
PMID- 9656480
TI - The mosaic nature of the eukaryotic nucleus.
AB - The phylogenies for each of the protein-coding genes from the Methanococcus
jannaschii genome were surveyed to determine the history of the major groups of
life. For each gene, homologous sequences from other archaea, eucarya, and Gram
positive and Gram-negative bacteria were collected and aligned, and a phylogeny
was reconstructed with a maximum-likelihood algorithm. The majority of
significant phylogenies favor the eucarya and the archaca as sister groups. A
smaller, but still substantial, portion of these significant phylogenies favor an
eucarya/Gram-negative clade. These results indicate that support for the early
history of life is not unequivocal. A chimeric origin of eukaryotes or an
ancient, massive horizontal transfer of genes from Gram-negative bacteria to
eucarya can explain many of the observed phylogenies.
PMID- 9656481
TI - Repeated evolution of an acetate-crossfeeding polymorphism in long-term
populations of Escherichia coli.
AB - Six out of 12 independent replicate populations of Escherichia coli maintained in
long-term glucose-limited continuous culture for up to approximately 1,750
generations evolve polymorphisms maintained by acetate crossfeeding. In all
cases, the acetate-crossfeeding phenotype is associated with semiconstitutive
overexpression of acetyl CoA synthetase, which allows for the enhanced uptake of
low levels of exogenous acetate. Mutations in the 5' regulatory region of the
acetyl CoA synthetase locus are responsible for all the acetate crossfeeding
phenotypes found. These changes were either transposable-element insertions or a
single T-->A nucleotide substitution at position -93 relative to the acs gene
translation start site.
PMID- 9656482
TI - Phylogenetic relationships and developmental expression of three sea urchin Wnt
genes.
AB - The Wnt genes comprise a family of secreted glycoproteins involved in cell-cell
signaling and pattern formation during the development of a variety of organisms.
We have begun to examine Wnt gene expression in sea urchins that exhibit
alternative modes of larval development but produce similar adults. Here we
describe the isolation of five Wnt sequences from indirect- and direct-developing
sea urchin species using a PCR-based strategy and library screening. Phylogenetic
and distance analyses indicate that the five sequences represent sea urchin Wnt
1, -4, and -5 orthologs. Wnt-5 sequences were isolated from three sea urchin
species and show a significantly faster rate of evolution than do their
counterparts in jawed vertebrates. The genomic structure of the Wnt-5 locus was
also examined, and its organization is similar to that of Wnt genes from insects
and vertebrates. The temporal expression of all three sea urchin Wnt orthologs
during sea urchin development was examined by RNA gel blots or RNase protection
assays. Transcripts from all three sea urchin Wnts are detected at various
developmental stages of both indirect- and direct-developing species. These data
support the view that sea urchin Wnt genes exhibit many conserved aspects and at
least three orthologs are developmentally regulated in both indirect- and direct
developing sea urchin embryos.
PMID- 9656483
TI - Long-range base pairing in Drosophila and human mRNA sequences.
AB - The potential for long-range base pairing between the 5' and 3' ends of mRNA
molecules was examined for 134 Drosophila and 204 human sequences collected from
the GenBank database. Each sequence was divided into two parts, a 5' sequence
taken from the start of the protein-encoding region and a 3' sequence taken from
the end of the transcript. The strongest RNA pairing stem between each pair of 5'
and 3' sequences was identified and scored using an alignment program modified to
incorporate RNA base pairing. The observed pairing scores were then compared with
a random distribution of scores generated by aligning each 5' sequence to random
permutations of its corresponding 3' sequence. For both the Drosophila and the
human mRNAs, the observed pairing scores were significantly biased toward the
upper tail of the random distributions, with 61% of the Drosophila sequences and
64% of the human sequences falling within the upper half of the random
distributions. This suggests that a pattern of long-range base pairing may be a
common feature of eukaryotic mRNAs. We have also analyzed a subset of Drosophila
and human mRNAs which show the greatest potential for long-range pairing. The
human pairings appear to be stronger and localized to more specific regions near
the ends of the mRNA sequence than those of Drosophila.
PMID- 9656484
TI - The evolutionary analysis of the Tnt1 retrotransposon in Nicotiana species
reveals the high variability of its regulatory sequences.
AB - We studied the evolution of the tobacco Tnt1 retrotransposon by analyzing Tnt1
partial sequences containing both coding domains and U3 regulatory sequences
obtained from a number of Nicotiana species. We detected three different
subfamilies of Tnt1 elements, Tnt1A, Tnt1B, and Tnt1C, that differ completely in
their U3 regions but share conserved flanking coding and LTR regions. U3
divergence between the three subfamilies is found in the region that contains the
regulatory sequences that control the expression of the well-characterized Tnt1
94 element. This suggests that expression of the three Tnt1 subfamilies might be
differently regulated. The three Tnt1 subfamilies were present in the Nicotiana
genome at the time of species divergence, but have evolved independently since
then in the different genomes. Each Tnt1 subfamily seems to have conserved its
ability to transpose in a limited and different number of Nicotiana species. Our
results illustrate the high variability of Tnt1 regulatory sequences. We propose
that this high sequence variability could allow these elements to evolve
regulatory mechanisms in order to optimize their coexistence with their host
genome.
PMID- 9656485
TI - Structural, genomic, and phylogenetic analysis of Lian, a novel family of non-LTR
retrotransposons in the yellow fever mosquito, Aedes aegypti.
AB - A retrotransposon named Lian-Aa1 was discovered in an intron of an AaHR3-1 gene
of the yellow fever mosquito, Aedes aegypti. This retrotransposon contained a
long open reading frame with 1,219 amino acids that included endonuclease,
reverse transcriptase, and RNase H domains. It was shown that in the Rock strain
of Ae. aegypti, there were up to 1,380 copies of Lian elements, equivalent to
0.8% of the entire genome. Five additional copies of Lian elements were isolated,
mapped by restriction digestion, and partially sequenced. The 5' and 3' ends of
the Lian family were determined by comparing the terminal sequences of the six
copies and were subsequently confirmed by the identification of putative target
duplications flanking Lian-Aa1 and Lian-Aa2. The Lian family is likely a novel
family of non-long-terminal-repeat (non-LTR) retrotransposons that terminate in a
repeat of (CTGA-TAC)2. On average, the six copies of Lian elements showed only
0.6% sequence divergence at the nucleotide level in both a 735-bp region at the
5' end and a 1,124-bp coding region. Genomic Southern blots also revealed a very
high degree of similarity among hundreds of Lian elements, suggesting very recent
activity of Lian. Furthermore, all six analyzed Lian elements were closely
associated with one or more different families of repetitive elements. It is
possible that these associations could reflect the complex relationship between
Lian elements and the rest of the Ae. aegypti genome. Phylogenetic analyses based
on the reverse transcriptase, domains of 36 non-LTR retrotransposons including
Lian-Aa1 identified five major subgroups that were supported by bootstrap
replications. In contrast to the majority of non-LTR retrotransposons, Lian-Aa1
has an RNase H domain that is similar to a few other non-LTR retrotransposons and
some retroviruses, which is consistent with the previously proposed independent
assortment of different domains during the evolution of retroelements.
PMID- 9656486
TI - Phylogenetic tests of the hypothesis of block duplication of homologous genes on
human chromosomes 6, 9, and 1.
AB - There are 10 gene families that have members on both human chromosome 6 (6p21.3,
the location of the human major histocompatibility complex [MHC]) and human
chromosome 9 (mostly 9q33-34). Six of these families also have members on mouse
chromosome 17 (the mouse MHC chromosome) and mouse chromosome 2. In addition,
four of these families have members on human chromosome 1 (1q21-25 and 1p13), and
two of these have members on mouse chromosome 1. One hypothesis to explain these
patterns is that members of the 10 gene families of human chromosomes 6 and 9
were duplicated simultaneously as a result of polyploidization or duplication of
a chromosome segment ("block duplication"). A subsequent block duplication has
been proposed to account for the presence of representatives of four of these
families on human chromosome 1. Phylogenetic analyses of the 9 gene families for
which data were available decisively rejected the hypothesis of block duplication
as an overall explanation of these patterns. Three to five of the genes on human
chromosomes 6 and 9 probably duplicated simultaneously early in vertebrate
history, prior to the divergence of jawed and jawless vertebrates, and shortly
after that, all four of the genes on chromosomes 1 and 9 probably duplicated as a
block. However, the other genes duplicated at different times scattered over at
least 1.6 billion years. Since the occurrence of these clusters of related genes
cannot be explained by block duplication, one alternative explanation is that
they cluster together because of shared functional characteristics relating to
expression patterns.
PMID- 9656487
TI - Inferring pattern and process: maximum-likelihood implementation of a
nonhomogeneous model of DNA sequence evolution for phylogenetic analysis.
AB - A nonhomogeneous, nonstationary stochastic model of DNA sequence evolution
allowing varying equilibrium G + C contents among lineages is devised in order to
deal with sequences of unequal base compositions. A maximum-likelihood
implementation of this model for phylogenetic analyses allows handling of a
reasonable number of sequences. The relevance of the model and the accuracy of
parameter estimates are theoretically and empirically assessed, using real or
simulated data sets. Overall, a significant amount of information about past
evolutionary modes can be extracted from DNA sequences, suggesting that process
(rates of distinct kinds of nucleotide substitutions) and pattern (the
evolutionary tree) can be simultaneously inferred. G + C contents at ancestral
nodes are quite accurately estimated. The new method appears to be useful for
phylogenetic reconstruction when base composition varies among compared
sequences. It may also be suitable for molecular evolution studies.
PMID- 9656488
TI - Nuclear gene trees and the phylogenetic relationships of the mangabeys (Primates:
Papionini).
AB - Phylogenetic relationships of mangabeys within the Old World monkey tribe
Papionini are inferred from analyses of nuclear DNA sequences from five unlinked
loci. The following conclusions are strongly supported, based on congruence among
trees derived for the five separate gene regions: (1) mangabeys are polyphyletic
within the Papionini; (2) Cercocebus is the sister taxon to the genus Mandrillus;
and (3) Lophocebus belongs to a clade with Papio and Theropithecus, with Papio as
its most likely sister taxon. Morphologically based phylogenies positing mangabey
monophyly were evaluated by mapping the sequences for each locus on these trees.
The data seem to fit these trees poorly in both maximum-parsimony and likelihood
analyses. Incongruence among nuclear gene trees occurred in the
interrelationships among Lophocebus, Papio, and Theropithecus. Several factors
that may account for this incongruence are discussed, including sampling error,
random lineage sorting, and introgression.
PMID- 9656489
TI - Sex-related genes, directional sexual selection, and speciation.
AB - Reproductive isolation and speciation can result from the establishment of either
premating or postmating barriers that restrict gene flow between populations.
Recent studies of speciation have been dominated by a molecular approach to
dissect the genetic basis of hybrid male sterility, a specific form of postmating
reproductive isolation. However, relatively little attention has been paid to the
evolution of genes involved in premating isolation and genes generally involved
in other sex-related functions (e.g., mating behavior, fertilization,
spermatogenesis, sex determination). We have assembled DNA sequences from 51
nuclear genes and classified them based on their functional characteristics. The
proportion of nonsynonymous to synonymous nucleotide substitutions were compared
between Drosophila melanogaster, Drosophila simulans, and Drosophila
pseudoobscura, as well as between Caenorhabditis elegans and Caenorhabditis
briggsae. We found a high ratio of nonsynonymous to synonymous substitutions for
sex-related genes (i.e., genes involved in mating behavior, fertilization,
spermatogenesis, or sex determination). The results suggest that directional
sexual selection has shaped the evolution of sex-related genes and that these
changes have more likely occurred during the early stages of speciation. It is
possible that directional selection becomes relaxed after reproductive isolation
has been completed between more distantly related species (e.g., D. melanogaster
and D. pseudoobscura). However, a saturation in the number of nucleotide
substitutions since the time of species separation may mask any sign of
directional selection between more distantly related species.
PMID- 9656490
TI - Evolutionary distances for protein-coding sequences: modeling site-specific
residue frequencies.
AB - Estimation of evolutionary distances from coding sequences must take into account
protein-level selection to avoid relative underestimation of longer evolutionary
distances. Current modeling of selection via site-to-site rate heterogeneity
generally neglects another aspect of selection, namely position-specific amino
acid frequencies. These frequencies determine the maximum dissimilarity expected
for highly diverged but functionally and structurally conserved sequences, and
hence are crucial for estimating long distances. We introduce a codon-level model
of coding sequence evolution in which position-specific amino acid frequencies
are free parameters. In our implementation, these are estimated from an alignment
using methods described previously. We use simulations to demonstrate the
importance and feasibility of modeling such behavior; our model produces linear
distance estimates over a wide range of distances, while several alternative
models underestimate long distances relative to short distances. Site-to-site
differences in rates, as well as synonymous/nonsynonymous and first/second/third
codon-position differences, arise as a natural consequence of the site-to-site
differences in amino acid frequencies.
PMID- 9656491
TI - A degenerate group II intron in the intronless mitochondrial genome of
Chlamydomonas reinhardtii: evolutionary implications.
PMID- 9656492
TI - A SINE that acquired a role in signal transduction during evolution.
PMID- 9656493
TI - The most ancient DNA recovered from an amber-preserved specimen may not be as
ancient as it seems.
PMID- 9656494
TI - The boiling point.
PMID- 9656495
TI - Cheers for eloquent 'right man syndrome' editorial.
PMID- 9656496
TI - Polypharmacy is not an example of scientific-based medicine, either.
PMID- 9656497
TI - Another look at 'the evil eye'.
PMID- 9656498
TI - Collaborators in care: the New England Center for Integrative Health blends
naturopathy and conventional medicine.
PMID- 9656499
TI - The psychosomatic network: foundations of mind-body medicine.
AB - Research in the 1980s uncovered ubiquitous neuropeptide-receptor distribution in
brain structures associated with emotional processing, and throughout many organ
systems. This finding supported neuropeptides as biochemical substrates of
emotion, and the neuropeptide-receptor network as a parasynaptic system crossing
traditional brain-body boundaries. The medical relevance of these findings was
affirmed by psychoneuroimmunology research: neuropeptides help to regulate
immunocyte trafficking, there is bidirectional communication between nervous and
immune system components, immunocytes produce neuropeptides, and nerve cells
produce immune-associated cytokines. In the past decade, the concept of a unified
psychosomatic network has been strengthened by animal and human research
demonstrating relationships between behavior and neuropeptide-mediated regulation
of immune functions. Research on emotional expression or disclosure in healthy
human subjects as well as in cancer and HIV-positive patients has shown
significant positive correlations with clinically relevant immune functions
and/or positive health outcomes. Psychosocial interventions emphasizing emotional
expression or active coping have evidenced survival benefits in breast cancer and
melanoma. These findings suggest that emotional expression generates balance in
the neuropeptide-receptor network and a functional healing system. Emotional
expression is also a marker for psychospiritual vitalization, and further
research should evaluate links between energy-based models of health and
neuropeptide-receptor-based models under the rubric of an informational paradigm.
PMID- 9656500
TI - The use of complementary medicine for healthy aging.
AB - By the year 2020, twenty percent of the US population will be aged 65 years or
older. The greatest growth in numbers will be among those aged 85 years or older.
If the healthcare demands of this group match those of their parents, it will
place an extraordinary burden on funding for medical services. By promoting
healthy aging, complementary medicine practitioners can improve the cost
effectiveness of healthcare delivery. A scientifically based complementary
medicine program to promote healthy aging includes (1) diet and nutritional
tailoring, (2) nutrient enhancement to meet specific individual needs, (3)
exercise training, (4) stress management, (5) promotion of structural integrity,
(6) environmental adjustment, (7) counseling on purposeful living, and (8)
normalizing intercellular communication. The program described in this article
incorporates these features and focuses on the following modifiable factors of
unhealthy aging: altered mitochondrial function and oxidative stress, increased
protein glycation, chronic inflammation, defects in methylation, reduced
detoxification ability, and altered immunity.
PMID- 9656501
TI - Psychological aspects of mind-body medicine: promises and pitfalls from research
with cancer patients.
AB - Research in psychosocial oncology has grown considerably. In this article,
psychological interventions for cancer patients are reviewed. The following four
areas are examined: (1) adjustment and quality of life, (2) symptom control, (3)
immune function, and (4) disease progression. In each area, psychosocial
dimensions of risk and resilience, the efficacy of current interventions, and the
trajectory of future developments are considered.
PMID- 9656502
TI - A multimethod research study on the use of complementary therapies among patients
with inflammatory bowel disease.
AB - CONTEXT: The purpose of this study was to gain a better understanding of the use
of complementary therapies among patients with inflammatory bowel disease.
OBJECTIVE: To examine factors influencing the use of complementary therapies, to
explore patient-physician communication concerning those therapies, and to assess
the effect of combining qualitative with quantitative research. DESIGN: In-depth
qualitative interviews. PARTICIPANTS: Fourteen patients were selected from a
quantitative study in which the use of complementary therapies among patients
with inflammatory bowel disease was assessed. RESULTS: Patients reported using
complementary therapies because of the serious side effects of medical treatment,
because they felt conventional treatments did not help, and because complementary
therapies were thought to be safe. Psychological and social factors for using
complementary therapies must be considered and understood. Patients cited many
reasons for not discussing the use of complementary therapies with their doctors.
Adding qualitative data to quantitative research greatly increased the authors'
understanding of factors that contribute to complementary therapy use.
CONCLUSIONS: Multiple factors contribute to the decision to use complementary
therapies among those with inflammatory bowel disease. Identifying these factors
is important for educating physicians regarding their patients' use of
complementary therapies and may contribute to improved patient-physician
communication.
PMID- 9656503
TI - A birth intervention: the therapeutic effects of Doula support versus Lamaze
preparation on first-time mothers' working models of caregiving.
AB - CONTEXT: A working model of caregiving has been defined as an internalized schema
of caregiving that guides a mother's behavior with her infant. This schema is
strongly influenced by the mother's first attachment relationship with her own
mother, which frequently operates outside her conscious awareness. OBJECTIVE: To
examine doula support at birth as an intervention that might correct distortions
of a mother's unconscious schema of caregiving, promoting more secure caregiving
following childbirth. DESIGN: The effects of doula support versus Lamaze birth
preparation on the working models of caregiving of 35 first-time pregnant mothers
were compared. INTERVENTIONS: An interview was used to assess the mothers'
working models in the third trimester of pregnancy and again 4 months after the
mothers gave birth. Mood state and self-esteem were measured at these times. A
post hoc analysis was performed on the mothers' birth experiences, the quality of
their postpartum support, and their evaluations of their infants' temperaments.
RESULTS: The prebirth to postbirth rating analysis of the interviews revealed
that the mothers in the doula group were significantly less rejecting and
helpless in their working models of caregiving than were the mothers in the
Lamaze group. The mothers in the doula group also showed greater security than
did mothers in the Lamaze group, a difference that approached but did not reach
significance. In addition, the women in the doula group were less emotionally
distressed and had higher self-esteem than did the women in the Lamaze group, and
the women in the doula group rated their infants as significantly less fussy than
the mothers in the Lamaze group rated their infants. CONCLUSIONS: When viewed in
the context of working models of caregiving, mothers who used a doula were
significantly less rejecting and helpless, and approached significantly higher
scores on the secure scale, than did mothers who used Lamaze birth preparation.
Mothers rated as secure showed significantly less mood disturbance and higher
prebirth and postbirth self-esteem than did mothers rated as insecure, providing
construct validity for the caregiving interviews.
PMID- 9656505
TI - Healing the practice of surgery.
PMID- 9656504
TI - Marilyn Schlitz, PhD. On consciousness, causation, and evolution. Interview by
Bonnie Horrigan.
AB - Marilyn Schlitz is an anthropologist and director of research for the Institute
of Noetic Sciences, where she develops and oversees research in three areas:
emerging worldviews, inner mechanisms of the healing response, and extended human
abilities. Before working for the Institute of Noetic Sciences, she was director
of the Esalen Center for the Theory and Research Working Group on Direct Mental
and Healing Interactions on Living Systems; a research associate in the
Department of Sociology and Anthropology at Trinity University in Texas; an
assistant research scientist at the Agricultural Research Station and Department
of Rural Sociology at Texas A & M University; and a research associate and
project director for the Mind Science Foundation. Dr Schlitz also has worked as a
research consultant for the Stanford Research Institute and as a research fellow
for the Foundation for Research on the Nature of Man at the Institute for
Parapsychology. She has taught at many universities and colleges, including work
as a lecturer in the Department of Psychology at Stanford, and as an instructor
in the Department of Sociology and Anthropology at Trinity University. In 1994
she received the Thomas Welton Stanford Psychical Research Fellowship. She
received her doctoral degree in anthropology from the University of Texas in 1992
and her master's degree in behavioral and social sciences in 1986, also from the
University of Texas. Dr Schlitz has published numerous papers and book chapters
on the topic of parapsychology. She speaks nationally and is involved with many
research projects exploring the relationship between consciousness and the outer
world.
PMID- 9656506
TI - [Physical activity and diabetes mellitus].
PMID- 9656507
TI - [Usual physical activity level, glycemic control, and cardiovascular risk factors
profile. Spanish Diabetes Society Working Group for the study of Nutrition].
AB - OBJECTIVES: To know the relation between the usual physical activity pattern and
metabolic control and cardiovascular risk factors of people with diabetes
mellitus. RESEARCH DESIGN AND METHODS: 144 type 1 (insulin dependent) diabetic
subjects (M/F, 70/74) and 193 type 2 (non insulin dependent) diabetic patients
8M/F, 81/112) fron DNCT study (Diabetes Nutrition and Complications Trial) were
included in the study from May 1993 to December 1994. Physical activity index was
assessed by means of the weekly caloric expenditure based upon previously
published questionnaire. RESULTS: At least 60% of diabetic patients had a regular
exercise more than 3 times per week. Unexpected, level of HbA1c, but not other
parameters, was related to the level of physical activity, in that the higher the
activity the higher HbA1c level in both type 1 and type 2 diabetic patients.
CONCLUSIONS: In the DNCT study the higher physical activity level was associated
a worsening in the HbA1c level. These un expected date there are take into
account when recommending physical activity to people with diabetes mellitus with
no good metabolic control.
PMID- 9656508
TI - [Prevalence of latent toxoplasma infection in HIV infection patients].
AB - BACKGROUND: To know the prevalence of Toxoplasma gondii latent infection in HIV-1
infected patients and to compare it with the prevalence in a group of parenteral
drug users, non-infected by HIV. METHODS: We study 255 HIV-1 patients revised in
our hospital in the last 6 years. The control group were 116 drug addicts non
infected by HIV followed in an educational program of deshabituation. We tested
IgG anti-toxoplasma by enzymatic inmunoessay (MEIA). An IgG plasma value of
6UI/ML or more was an indicative of toxoplasma previous infection. We used Chi
Square and Yatchts correction tests for the statistical analysis, settling down a
significance point of 95%. RESULTS: We founded 36.7% positive IgG anti-toxoplasma
in the group on HIV-1 infected patients, non drugs addicts, against 30.9% in the
group of HIV-1 drug addicts patients. (OR 0.77; 0.35 < OR < 1.66). The control
group showed a Toxoplasma seroprevalence of 26.7%, without statistically
significant against the drug addicts HIV group (OR = 1.55; 0.93 < OREGON < 2.59).
CONCLUSIONS: The seroprevalence of Toxoplasma gondii latent infection in our
study was similar to the european results. We didn't found a higher prevalence in
HIV-1 patients than in patients non infected by HIV-1.
PMID- 9656509
TI - [Visceral leishmaniasis in immunocompromised patients].
AB - OBJECTIVE: Most patients who developed visceral leishmaniasis (VL) in our country
are immunocompromised (IC) host, frequently HIV-infected patients. One objective
was to know if there were differences about the clinical manifestations,
diagnostic tests or prognosis in IC patients who were infected or not with HIV
(HIV+ and HIV-, respectively). Also we wonder if some features were associated
with death during the initial episodes of VL. METHOD: We studied 16 IC patients
with VL, 9 were VIH+ and 7 were VIH-. Most frequently observed findings were
fever (94%), splenomegaly (81%), hepatomegaly (69%), and constitutional syndrome
(50%). HIV+ patients had symptoms during a lapse of time (70 +/- 78 days) larger
than the VIH- cases had (17 +/- 12 days, p < 0.05). RESULTS: We performed a
serology to Leishmania sp in 15 cases (94%) and were positive in 13 patients (77%
in HIV+ and 100% in VIH patients). Seven patients (44%, 4 VIH- and 3 VIH+) died
during the initial episode of VL. Nine patients (66%) who survived to it were
followed-up during 68 +/- 49 months. Seven patients (4 VIH+ and 3 VIH-) showed
several relapses (2.5 +/- 1.6 relapses/patient) through the follow-up. The
patients who died during the initial episode had more frequently (p < 0.05)
concentrations of albumin below 3 g/dl or of globulins below 4 g/dl, than the
survivors had. The CD4+ lymphocyte counts in HIV+ patients were lower in patients
who died during the initial episode of VL (19 +/- 15/mm) than in survivors (108
+/- 67/mm3, p = 0.07).
PMID- 9656510
TI - [Decisions regarding cholesterol-lowering therapy in the elderly: the experience
in a lipid clinic and a review of the literature].
AB - BACKGROUND: Therapy for hypercholesterolemia is long known one of the
interventions with higher benefit on coronary heart disease secondary prevention
and on primary prevention in middle-age high-risk people. Data about elderly
persons are more scarce. The aim of this work is to study elderly patients sent
to a Lipid Clinic, focusing on Serum Lp (a) levels and criteria to prescript
cholesterol-lowering drugs. We have reviewed current knowledge to discuss and to
clarify these criteria. METHOD: Observational study. Review of the medical charts
from the patients sent to the Lipid Clinic. Elderly patients were compared with
middle-aged persons attended to the same Clinic. RESULTS: From 348 total Lipid
Clinic cohort 72 (20.7%) patients were more than 65 years old (31 male). A 3
months or longer follow-up was available in 49/72 and 36/49 were taking
cholesterol-lowering drugs. Among these 36, 21 had coronary disease; the other 15
had, at least, another risk factor, besides dyslipidemia. Serum Lp (a) level were
higher in older group (38.7 +/- 36.9 mg/dl, median 29, vs 26.3 +/- 24.2, median
18 mg/dl, p < 0.01). Considering the accepted cardiovascular risk threshold (Lp
(a) > 30 mg/dl), difference were found only in women. Coronary disease was
present in 79 patients followed 3 months or longer and 24/79 were more than 65
years old. Twenty-one of them were taking cholesterol-lowering drugs, vs 50 from
the 55 younger (pNS). The reasons for no drug-therapy were similar in both
groups. CONCLUSIONS: Coronary heart disease or cardiovascular risk factors
association were the criteria used for starting cholesterol-lowering drug
therapy. Published evidence supporting this therapeutic approach is reviewed.
There were not found age related differences for cholesterol-lowering drugs
prescriptions in patients suffering coronary disease. Serum Lp (a) level were
higher in elderly sample because of the increase in older women; it could be
linked to the postmenopausal hormonal state.
PMID- 9656511
TI - [Vasculitis affecting the kidney: analysis of 18 patients].
AB - OBJECTIVE: Eighteen patients who were judged to have systemic vasculitis (1990
American College of Reumathology criteria) affecting the kidney, from January
1988 to August 1996, were reviewed. METHOD: We analyzed characteristics of
clinical, biochemical, histopathological features, the interval between the onset
of the symptoms to a diagnosis of disease, treatment and overall outcome.
RESULTS: The principal mode of presentation of the vasculitis is general, renal
and pulmonary symptoms. The discovery of ANCA has improved the diagnostic
procedure in patients with these diseases. Renal biopsy facilitates early
diagnosis, prognosis and treatment. The renal lesion typically shows a segmental
necrotizing glomerulonephritis and extracapillary proliferation forming crescent.
CONCLUSIONS: The systemic vasculitis with renal involvement carries a poor
prognosis and high mortality. A variety of treatment has been employed, but their
precise role in the management of these vasculitis is still being elucidated.
PMID- 9656512
TI - [Massive hepatic amyloidosis: a case of hepatic failure and haemorrhagic
pancreatitis of fatal evolution].
AB - Hepatic involvement is frequently in systemic amyloidosis but major clinical
symptoms due to portal hypertension or liver failure are rare. To date all
treatment modalities proven in these patients have failed. Thus, prognosis is
dismal with progressive deterioration in liver function. We describe a patient
with massive liver involvement by primary amyloidosis, manifested by severe
intrahepatic cholestasis. Up to now 25 similar case have been reported in the
English literature. In this subset of patients the most frequently recorded cause
of death was renal failure accelerated by hyperbilirrubunemia. In our patient a
downhill course was characterized by fatal renal hepatic failure after an
hemoperitoneum, probably as a delayed complication of liver biopsy. Although not
all authors agree, an added risk of bleeding after liver biopsy have been pointed
out in hepatic amyloidosis. This kind of problem recommends the use of tissue
other than liver, or a transjugular hepatic biopsy for diagnostic purposes. Also,
of interest in the present cause is the autopsy findings of pancreatitis
associated to pancreatic amyloidosis, a complication which have been described in
previous reports.
PMID- 9656513
TI - [Primary tracheobronchial amyloidosis. Report of a case].
AB - We present a patient with primary tracheobronquial amiloidosis diffuse,
presenting with asthma-like dysnea. The diagnosis was made through the
broncoscopy and biopsy of infiltrated bronchial mucosa.
PMID- 9656514
TI - [T-gamma lymphocytosis associated with two solid neoplasms in a patient with
rheumatoid arthritis].
AB - T gamma lymphocytosis is an infrequent entity, generally benign and distinct of
the spectrum of the T cell chronic lymphoproliferative syndromes, that it not
need or need short therapy, with a prolongated survival. T gamma lymphocytosis is
expressive in the most of the occasions of a monoclonal lymphocytic proliferation
and it is frequently associated to Rheumatoid Arthritis. We present the case of a
patient with T gamma lymphocytosis, developed after several years of evolution of
Rheumatoid Arthritis and that it was coincident with two solid neoplasms, an
infiltrate carcinoma of the larynx and recurrent urothelial carcinoma, without
previous chemotherapy. The death in this patients, is generally due a progressive
lymphoproliferation and sepsis relationed with the neutropenia.
PMID- 9656515
TI - [Acute pancreatitis complicating primary HIV-1 infection].
AB - Primary HIV infection is usually paucisymptomatic, although 30-40% of patients
show a mononucleosic syndrome of variable intensity and different manifestations.
An increasing number of heterosexual HIV infection in Spain, and the fact of more
severe manifestations in this subset of patients make necessary a deeper
understanding of this complex clinical picture. We report a case of heterosexual
primary HIV infection in a female patient without any known risk factor. This
care evolued in an exceptionally severe form with meningitis and pancreatitis, to
the best of our knowledge, this is the first reported care of pancreatitis
complicating primary HIV-1 infection.
PMID- 9656516
TI - [Coeliac disease in the adult].
AB - Coeliac disease can by defined as a chronic disease characterized by a typical
mucosal lesion of the small intestine and an impaired nutrient absorption which
improves on withdrawal of gluten from the diet. The prevalence rate has increased
over the last decades and just 1/3 of cases are diagnosed in childhood. There is
a striking association with class II histocompatibility antigens, HLA-DR3 and HLA
DQ2. Cellular immune response mediated by intraepithelial and lamina propria
lymphocytes is the primary event in the small intestine damage. Up to 50% of
adult coeliac patients don't present intestinal symptoms being more frequent
subclinic forms. The immunological markers of coeliac disease are antigliadin,
antireticulin and antiendomysial antibodies, being the last one the most
specific. Mortality of coeliac patient is increased mainly for malignancies,
being the most frequent the intestinal T lymphoma.
PMID- 9656517
TI - [Value of rationalization in the clinical use of antibiotics].
PMID- 9656518
TI - [Varicella pneumonia in healthy adults. Apropos of 7 cases].
PMID- 9656519
TI - [Tuberculous pancreatitis in HIV infection].
PMID- 9656520
TI - [Autoimmune thrombocytopenia from low molecular weight heparin].
PMID- 9656521
TI - [Multiple cutaneous tumors as the first manifestation of lung adenocarcinoma].
PMID- 9656522
TI - [Tuberculosis in HIV infected patients].
PMID- 9656523
TI - [Severe hemolytic anemia secondary to cytomegalovirus infection in an
immunocompetent adult].
PMID- 9656524
TI - [Tuberculosis in the elderly].
PMID- 9656525
TI - [Adverse reactions to insulin].
PMID- 9656526
TI - [Gastric carcinoma in patients younger than 35 years of age].
PMID- 9656528
TI - [Septic shock and multiple organ failure from Mycobacterium tuberculosis].
PMID- 9656527
TI - [Norwegian scabies and sepsis from Escherichia coli in a HIV infected patient].
PMID- 9656529
TI - [Norwegian scabies in patients with AIDS. Primary prophylaxis in a possible
hospital outbreak].
PMID- 9656530
TI - [Treatment of chronic viral hepatitis].
PMID- 9656531
TI - [Antiretroviral treatment of HIV infection in children].
PMID- 9656532
TI - [Diagnostic value of reactive C protein in suspected acute appendicitis in
children].
AB - OBJECTIVE: The aim of this study was to evaluate the accuracy of C-reactive
protein (CRP) measurements in the diagnosis of suspected acute appendicitis (AA)
during childhood. PATIENTS AND METHODS: A prospective study of 195 consecutive
children, aged between 2 and 14 years and suspected of having AA, that attended a
pediatric emergency room was carried out. We obtained a careful patient history,
physical signs, blood test results, final diagnosis and the histological findings
in the cases who underwent appendectomy (classified as normal appendix, simple
appendicitis (SA) or gangrenous appendicitis (GA). RESULTS: The final diagnoses
and their frequencies were: AA (94), non-specific abdominal pain (80), mesenteric
lymphadenitis (6) and others (15). Appendectomies were performed in 103 cases
with 94 cases being AA (91.3%) and of these 51 SA and 43 GA. The average values
of CRP (mg/l) were: AA: 30, SA: 16, GA: 67, non-specific abdominal pain: 15, and
mesenteric lymphadenitis: 44 (p < 0.01). The values of AG were statistically
higher than those of SA (p = 0.0000). The ROC curve of these data determined the
best cut-off levels for AA to be 30 (sensitivity: 0.43, specificity: 0.92,
predictive value of a positive result: 0.87 and predictive value of a negative
result: 0.58). CONCLUSIONS: 1) The value of CRP in AA is higher than in other
abdominal pain etiologies. Nevertheless, this value should not be used to deny
surgery since it is often normal in SA. 2) When a CRP value > 40 mg/L is found in
a suspected AA, one should think about GA and therefore, initiate prophylactic
antibiotics and perform surgery immediately.
PMID- 9656533
TI - [Eyberg inventory of child behavior. Standardization of the Spanish version and
its usefulness in ambulatory pediatrics].
AB - OBJECTIVE: Taking into account the high prevalence of behavioral problems in the
pediatric outpatient clinic, a need for a useful and easy to administer tool for
the evaluation of this problem arises. The psychometric characteristics of the
Spanish version of the Eyberg Behavioral Child Inventory (EBCI), [in Spanish
Inventario de Eyberg para el Comportamiento de Nino (IECN)], a 36-item
questionnaire were established. PATIENTS AND METHODS: The ECBI
inventory/questionnaire was translated into Spanish. The basis of the ECBI is the
evaluation of the child's behavior through the parents' answers to the
questionnaire. Healthy children between 2 and 12 years of age were included and
were taken from pediatric outpatient clinics from urban and suburban areas of
Barcelona and from our hospital's own ambulatory clinic. RESULTS: The final
sample included 518 subjects. The mean score on the intensity scale was 96.8 and
on the problem scale 3.9. Internal consistency (Cronbach's alpha) was 0.73 and
the test-retest had an r of 0.89 (p < 0.001) for the intensity scale and r = 0.93
(p < 0.001) for the problem scale. Interrater reliability for the intensity scale
was r = 0.58 (p < 0.001) and r = 0.32 (p < 0.001) for the problem scale.
Concurrent validity between both scales was r = 0.343 (p < 0.001). CONCLUSIONS:
The IECN is a useful and easy tool to apply in the pediatrician's office as a
method for early detection of behavior problems.
PMID- 9656534
TI - [Ophthalmoplegia-ataxia-areflexia in pediatrics. Three new patients and review of
the literature].
AB - OBJECTIVE: The objective of this study was to investigate if pediatric patients
with benign brainstem encephalitis (Bickerstaff Syndrome) or with Miller-Fisher
Syndrome are the extremes of the same nosological entity which, in adults, has
been named ophalmoplegia-ataxia-areflexia syndrome. PATIENTS AND METHODS: The
subjects included in the study were three patients of our institution and 24
patients found in the revision of the English and Spanish pediatric literature
who fulfilled the diagnostic criteria of ophtalmoplegia-ataxia-areflexia
syndrome. The topographical location of the lesion in the nervous system was
based on previously established criteria by using clinical and complementary
studies. RESULTS: Of the 27 patients included in the study we were able to reach
an accurate topographical diagnosis in 9. None had an exclusive involvement of
the peripheral nervous system, (6) had exclusively central nervous system
involvement and 2 showed involvement of both system. In 12, the topographical
location of the lesion could be only ascertained as probable; 3 of them in the
peripheral nervous system, 2 in the central nervous system and mixed involvement
in 7. In the remaining 7 patients there were insufficient clinical data to allow
topographical classification. CONCLUSIONS: The ophtalmoplegia-ataxia-areflexia
syndrome can also be found in pediatric patients. The lesion in the majority of
patients in this age group is located in the central nervous system, either alone
or combined with peripheral nervous system involvement.
PMID- 9656535
TI - [Juvenile spondyloarthropathies: descriptive study of 40 patients].
AB - OBJECTIVE: The objective of this study was to describe the clinical
characteristics of children with spondyloarthropathies diagnosed in our unit.
PATIENTS AND METHODS: We analyzed the patients with SEA syndrome,
undifferentiated spondyloarthropathy, psoriatic arthritis, arthritis associated
with inflammatory bowel disease and reactive arthritis with onset symptoms before
the age of 16. RESULTS: Forty patients were diagnoses as suffering from
spondyloarthropathy (29 boys and 11 girls). Eight presented a SEA syndrome, 8
undifferentiated spondyloarthropathy, 8 psoriatic arthritis, 6 arthritis
associated with inflammatory bowel disease and 10 with reactive arthritis. No
patient met ankylosing spondylitis criteria. In ten children the initial
diagnosis was chronic juvenile arthritis. The articular disease had a relapsing
and remitting course in one third of the patients. Almost 50% had only one
episode and 7 patients had one prolonged course. In general, the functional
outcome was good. CONCLUSIONS: Juvenile spondyloarthropathies are a group of
rheumatic diseases with common clinical characteristics and differ from chronic
juvenile arthritis. Their early recognition is important with regard to treatment
and prognosis.
PMID- 9656536
TI - [Bacterial meningitis in pediatrics. Study of 166 cases].
AB - OBJECTIVE: The purpose of this study was to evaluate the clinical and
epidemiological characteristics of meningitis in our environment. PATIENTS AND
METHODS: A retrospective study of 166 cases of meningitis diagnosed in our
hospital during a 10 year period (1986-1995) was performed. The patients were
between 1 month and 14 years of age. RESULTS: Sixty-six percent of the patients
were male and 34% female. Eleven cases were younger than 2 months (6.6%), 122
cases (73.5%) were between 3 months and 5 years of age and 33 cases (19.9%) were
older than 5 years. The most frequent symptoms and signs were fever (96%),
vomiting (60%), impairment of consciousness (24%) and meningeal signs (49%). CSF
cultures were positive in 52% and blood cultures in 32%. The pathogen isolated
was N. meningitidis in 53 cases (32%), H. influenzae in 38 (23%), S. pneumoniae
in 9 patients (5%) and others in 3 children (2%). Meningitis due to H. influenzae
increased each year. No microorganism was isolated in blood and CSF in 63 cases
(38%). Meningitis in children between 3 months and 5 years of age was due to N.
meningitidis in 40 children (33%) and H. influenzae in 36 (29%). The mortality
rate was 3%. The most frequent complications were sepsis (36%) and seizures
(16%). CONCLUSIONS: The most frequently isolated agent in our study was N.
meningitis. Meningitis due to H. influenzae is increasing such that H. influenzae
and N. meningitis currently show similar frequency in children between 3 months
and 5 years of age.
PMID- 9656537
TI - [Frequency and current clinical diversity of cerebral cortical dysgenesis].
AB - OBJECTIVE: The extended use of MRI has increased the number of patients diagnosed
of cortical dysgenesis and has changed the clinical spectrum usually associated
with this disorder. The aim of this study was to know the frequency and clinical
variety of cortical dysgenesis in our current patient population. PATIENTS AND
METHODS: All patients with dysgenesis of the neocortex or of the hippocampus,
according to radiological or pathological features, were selected from the total
number of patients attended during 1996 at an outpatient hospital-based
neuropediatric clinic. Malformations of cerebellar cortex and neurocutaneous
syndrome were excluded. RESULTS: Twenty-one patients (1.3% of all patients
attended at the clinic) studied by MRI showed polymicrogyria (43%) which was of
perisilvian localization in three patients, heterotopias (33%), dysplasia of the
hippocampus (24%), agyria-pachygria (14%) and hemimegaencephalia (5%). Three
patients underwent surgical interventions. Epilepsy was present in 90%, mental
retardation in 68%, cerebral palsy 47%, infantile spasms 40%, microcephally 25%,
autism 10%, hyperkinesis 5% and learning disabilities in 33% of those school age
children free of mental retardation. CONCLUSIONS: The actual prevalence of
cortical dysgenesis at our clinic is similar to that of neurodevelopmental
impairments following birth-asphyxia (1.2%), amounting to two thirds of those
following prematurity and to half of those following a brain injury of late
prenatal onset. Except for the almost constant presence of epilepsy, especially
infantile spasms, clinical symptomatology is diverse and occurs in a similar
percentages in brain lesions acquired during labour or during late pregnancy.
Hyperkinesis and autism have a similar prevalence to that seen in the total
number of patients attended at the clinic during 1996.
PMID- 9656538
TI - [Secondary effects of prostaglandin E1 on the management of hypoplastic left
heart syndrome while waiting for heart transplantation].
AB - OBJECTIVE: Newborns with hypoplastic left heart syndrome (HLHS) included in the
heart transplant program depend on continuous prostaglandin E1 (PGE1) perfusion
for a prolonged period of time, which can result in various side effects. The
objective of this study was to analyze the side effects derived from the use of
PGE1 in newborns with HLHS who are awaiting heart transplantation. PATIENTS AND
METHODS: Fifteen newborns with HLHS included in a cardiac transplant program
between January 1993 and August 1996 were studied. All received continuous
endovenous perfusion of PGE1 from the time of diagnosis of the cardiopathy.
RESULTS: Thirteen patients were transplanted, with 6 dying in the operating room.
Seven survived. Two patients died while waiting for a transplant. All presented
short term side effects derived from the continuous perfusion of PGE1, including
a slight fever and irritability. However, none of them presented apnea pauses.
Cortical hyperostosis and anthral hyperplasia were observed in 13 (83.3%) and 12
(80%) cases, respectively, but in all transplanted cases regression of the
anthral hyperplasia was seen after 6 months and regression of the cortical
hyperostosis was seen after 12 months. CONCLUSIONS: PGE1 was effective in
maintaining the permeability of the ductus arteriosus. The side effects derived
from the treatment were well tolerated. The appearance of cortical hyperostosis
and anthral hyperplasia is related to the duration of the perfusion and these
disappear in the weeks following the suspension of PGE1 treatment.
PMID- 9656539
TI - [Jarcho-Levin and Casamassima syndromes: differential diagnosis and frequency in
Spain].
AB - OBJECTIVE: Jarcho-Levin syndrome is characterized by the presence of only costal
vertebral defects. However, this diagnosis has been used in any case presenting
with costovertebral defects, whether associated to other congenital defects or
not. Recently, it has been demonstrated that costovertebral defects constitute a
developmental field defect and, because of this, they can be observed in
different clinical and etiological patterns. On the other hand, Casamassima
syndrome is characterized by the presence of costovertebral defects, genito
urinary anomalies and anal atresia, which make it easily distinguishable from
Jarcho-Levin syndrome. PATIENTS AND METHODS: We present the cases with Jarcho
Levin and Casamassima syndromes identified among 1,405,374 liveborn (LB) infants
registered by the Spanish Collaborative Study of Congenital Malformations
(ECEMC). RESULTS: Frequencies of these two syndromes in the ECEMC are 0.2 per
100,000 LB for Jarcho-Levin syndrome and 0.3 per 100,000 LB for Casamassima
syndrome. We present the clinical manifestations and other characteristics of all
the cases registered with these syndromes in the ECEMC. CONCLUSIONS: Jarcho-Levin
syndrome is defined by the presence of costoveriebral defects without any other
congenital defect. However, given that the alterations of the axial skeleton are
a developmental field defect, they can be observed in different clinical
etiological patterns that should not be considered as Jarcho-Levin syndrome.
Among these, Cassamassima syndrome can be clearly distinguished, being autosomal
recessive as is Jarcho-Levin syndrome.
PMID- 9656540
TI - [Absorptive pattern of individual fatty acids and total fat in full term babies.
Its stability in the absence of lactose].
AB - OBJECTIVE: Lactose absence implies a decrease in calcium absorption. If not
absorbed, calcium soaps can be produced with the intestinal fatty acids.
Absorption and retention of total fat, individual fatty acids, calcium, magnesium
and phosphate have been compared between two groups of children, one fed with
lactose free formula and higher levels of calcium (FSL) and the other with
standard starting formula (FI). None of them had additional arachidonic or
docosahexaenoic acids. PATIENTS AND METHODS: A randomized prospective study was
made on 19 term newborn babies by means of metabolic balance measurement during
an 8 day period (four days of a stabilization period on the formula, 3 days of
the balance period and the final day for feces collection). Both groups were
selected following the same criteria for gestational age, balance age, and weight
and length at both time periods. Aliquos from the formula were collected daily,
as well as all feces and urine during the balance period. Calcium and magnesium
quantification of the corresponding ashed products was performed by means of
atomic absorption, while Pi was with a colorimetric assay. Total fat was
extracted by organic solvents and quantified by gravimetry. Lipid phase fatty
acids were methylated, extracted and quantified by means of gas chromatography
with a detector of flame ionization. RESULTS: Total fat content and the
percentages of each fatty acid did not differ, only calcium concentration in FSL
was slightly higher (64.9 +/- 6.9 vs 58.9 +/- 7.0 mg/100 g). No differences were
found between groups in relation to ingestion, excretion and retention. The
percentages of calcium and total fat retention, however, were slightly superior
in the FI in relation to the FSL group. Ca: 68 +/- 22 mg/kg/d, 49 +/- 14% vs 56
+/- 23 mg/kg/d, 48 +/- 17% and total fat: 6.6 +/- 1.2 g/kg/d, 92 +/- 8% vs 6.8 +/
1.5 g/kg/d, 90 +/- 9%. Absorption of MC fatty acids was 99% for C8. Linoleic and
alfalinolenic acid showed an absorption of around 90% despite the big differences
in their intake (10/1). Net retention of linoleic acid was 933 +/- 168 mg/kg/d
(FI) and 963 +/- 190 mg/kg/d (FSL) and the amount of alpha-linolenic acid was 95
+/- 16 (FI) and 100 +/- 22 mg/kg/d (FSL). No correlation could be found between
the amount of excreted calcium and the total amount of fat in feces or with any
of the fatty acids studied. This was true for each group studied separately or
when considered as a single group. CONCLUSIONS: The absorptive pattern of fatty
acids in full term babies, when quantified did not show any conspicous
alterations in relation to the accepted values of other ages. The absence of
lactose (FSL) in a formula does not make any change in the absorption of total
fat and the individual fatty acids when compared to lactose containing formula
(FI), when these are present in the same proportions. Supplemented calcium in the
formula without lactose could compensate for its lower absorbtion. The absorptive
pattern of fatty acid in full term babies did not show any conspicuos alterations
in relationship to the accepted values of other ages.
PMID- 9656541
TI - [Syringomyelia, Chiari's malformation and scoliosis in a patient with type 1
neurofibromatosis].
PMID- 9656542
TI - [Multidisciplinary treatment without major plastic surgery of complicated
neonatal postoperative mediastinitis].
PMID- 9656543
TI - [Mounier Kuhn syndrome: clinical course of a case in childhood].
PMID- 9656544
TI - [Congenital cutis marmorata telangiectatica. Report of a new case].
PMID- 9656545
TI - [Electric burns of the mouth. Their impact in childhood].
PMID- 9656546
TI - [Hypertransaminasemia as first manifestation of celiac disease].
PMID- 9656547
TI - [Subcutaneous nodules in a newborn child].
PMID- 9656548
TI - [Acute pain, analgesia, and sedation in children (IIIb): pharmacokinetics and
pharmacodynamics of sedatives].
PMID- 9656549
TI - [Study of pediatric massage].
PMID- 9656550
TI - [Research training in the postgraduate period].
PMID- 9656551
TI - [Kinetics of in vitro clonal growth of the murine MB-49 bladder tumor cell line].
AB - OBJECTIVE: To analyze the in vitro growth kinetics of the MB-49 murine bladder
tumor cell line. METHODS: Cell proliferation and duplication time (DT) were
determined by 595 nm absorbance analysis and hemocytometry with and without fetal
calf serum (FCS). RESULTS: The 595 nm absorbance and the hemocytometer cell count
correlated according to the linear equation of cell number = 595 nm absorbance x
334.110-8.795 (r = 0.98). Cell proliferation was significantly higher in cultures
with FCS (p < 0.001). However, a significant increase in the cell count (p <
0.01) was observed after 24 hours in cultures with and without FCS. DT was 21 and
50 hours for cultures with and without FCS, respectively. CONCLUSION: This
experiment confirms the nature of the tumor cells and permits establishing the
precise growth conditions of the MB-49 cells in this laboratory.
PMID- 9656552
TI - [Reduction of hospital stay, because of the early removal of the bladder catheter
in transurethral resection of the prostate].
AB - OBJECTIVE: To analyze the effects of removal of the bladder catheter 48 hours
following transurethral resection of the prostate for benign prostatic
hyperplasia in relation to the length of hospital stay and the incidence of
important postoperative complications. METHODS: A study was conducted on 117
patients who had undergone TURP at our hospital over a period of one year. They
were divided into two groups: group I comprised 55 patients in whom the bladder
catheter had been systematically removed 48 hours following the procedure and had
been discharged from hospital once they had attained a satisfactory micturition;
group II comprised 62 patients in whom the bladder catheter was removed following
conventional practice. RESULTS: The mean length of hospital stay for the early
catheter removal group was 2.02 days versus 3.85 days for group II. The
postoperative complication rate was similar for both groups. CONCLUSIONS: Early
removal of the bladder catheter following TURP does not increase the complication
rate. It shortens the length of hospital stay and reduces the cost of the
procedure.
PMID- 9656553
TI - [Mumps orchitis; review of 8 cases].
AB - OBJECTIVE: To determine the incidence of mumps orchitis in young males in the
area of El Bierzo (Ponferrada, Spain) and the complications arising from this
condition. METHODS: The cases of mumps orchitis referred by the primary care
services to the emergency services of Hospital del Bierzo referral center were
reviewed. We analyzed patient age, unilateral or bilateral testicular
involvement, whether the patients had been vaccinated against mumps and the
changes observed in the semen analysis. RESULTS: The diagnosis of mumps orchitis
was confirmed in 8 patients, aged 15 to 19 years. Two patients had bilateral
testicular involvement. Seven patients had not been vaccinated against
parotiditis. Three patients had oligoasthenospermia and are currently being
followed at the Urology services. CONCLUSIONS: The utility of large scale
vaccination against mumps is emphasized. Long-term follow-up is recommended for
all patients with abnormal semen analysis, particularly those with bilateral
testicular involvement, since they may develop oligoasthernospermia several years
after the infection or improve with item. A high incidence of mumps orchitis was
found for this 12-month study period.
PMID- 9656554
TI - [Ureteral bladder augmentation. Report of 5 cases].
AB - OBJECTIVES: To describe 5 cases of ureteral bladder augmentation. METHODS: From
may 1995 to september 1997, ureterocystoplasty was performed on 5 patients (3
males and 2 females), aged 2 to 18 years (mean 9.8). The mean follow-up was 16.6
months (range 4-28). RESULTS/CONCLUSION: Augmentation ureterocystoplasty has the
beneficial effects of enterocystoplasty without the complications that may arise
from the use of bowel segments. It is a simple surgical technique whose outcome
depends entirely on careful patient selection.
PMID- 9656555
TI - [Abdominal pain in patients undergoing radical cystectomy for bladder cancer].
AB - OBJECTIVE: To analyze the incidence and causes of emergency admission for
abdominal pain in patients submitted to radical cystectomy for bladder cancer.
METHODS: A retrospective study was conducted on 176 patients who had undergone
radical cystectomy for bladder cancer. The preoperative treatment, urinary
diversion procedure, postoperative tumor stage, complications and adjuvant
treatment required were analyzed. The patients had a follow-up of 43.7-58.3
months (mean 51). RESULTS: 18 patients required admission for abdominal pain; 7
for complete bowel obstruction, 5 for partial obstruction of the intestine and 6
for intestinal fistula (4 to the neobladder, 1 to the urethra, and 1 to the
vagina). In 6 patients abdominal pain was caused by recurrence of a pelvic tumor.
Seven patients required emergency surgery and 5 elective surgery. CONCLUSIONS:
10.5% of the patients who had undergone radical cystectomy for bladder cancer had
at least one episode of abdominal pain requiring admission to hospital. During
the first 6 months postoperatively, partial obstruction of the intestine was the
most common cause of abdominal pain, and thereafter, complete bowel obstruction
and intestinal fistula to the neobladder. Abdominal pain was caused by recurrence
of a pelvic tumor in 33% of the patients and by a benign condition in the
remaining patients. We found no risk factors related with the preoperative
treatment, tumor, urinary diversion procedure or early complications that may
predispose to episodes of abdominal pain.
PMID- 9656556
TI - [Incidence and risk factors for calculi formation in patients treated with
augmentation cystoplasty or intestinal substitution].
AB - OBJECTIVE: Bladder stones have been observed more frequently in patients
undergoing bladder augmentation or substitution than in the normal population. We
analyzed the etiological factors influencing bladder stone formation in patients
submitted to the foregoing procedures. METHODS: Between December 1986 and October
1994, 12 augmentation cystoplasties with detubularized ileum or colon (group I)
and 24 substitution ileocystoplasties (group II) were performed. None of the
patients were known to have urinary stone formation. The possible causes of
bladder stone formation were analyzed in both patients groups. The patients were
evaluated for urinary infection, post micturition bladder residue, urinary pH,
and stone forming metabolic alterations in blood or urine. The latter consisted
in determining the blood levels of creatinine, calcium, uric acid and phosphorus
and the 24-hr urine levels of calcium uric acid, phosphorus, creatinine, urea,
oxalic acidi citric acid and magnesium. The statistical analysis consisted of an
unweighted logistic regression test and a chi square test between each of the
above variables and the existence of bladder stones. RESULTS: In group I, 10
patients revealed recurrent urinary infections, 0 showed a significant post
micturition bladder residue, a pathologically alkaline pH was observed in 2 and
the metabolic study of blood and urine revealed alterations in 9 patients. In
group II, 18 patients revealed recurrent urinary infection, 13 patients had post
micturition bladder residue, a pathologically alkaline pH was observed in 1, and
the metabolic study of blood and urine revealed alterations in 13 patients. The
statistical analysis using the unweighted logistic regression test showed no
significant relation between any of the parameters and the presence of stones,
for the substitution group pr augmentation group. However, the chi-square test to
determine the relation between the different varikables and the existence of
stones, showed a statistically significant relation between an elevated urinary
pH, recurrent urinary infection, post-micturition bladder residue and bladder
stone formation for groups I. Concerning the type of suture employed, some degree
of relation between the use of non-resorbable suture and stone formation was
found, although it was not statistically significant. CONCLUSION: We can
therefore conclude that urinary pH, recurrent urinary infection annd post
micturition bladder residue, and probably use of nonreabsorbable suture, are
among the etiological factors that we should avoid and treat in order to prevent
the formation of bladder stones in patients undergoing augmentation or
substitution cystoplasty.
PMID- 9656557
TI - [Which treatment should children with recurrent urinary infections, without
anatomical anomalies, receive?].
AB - OBJECTIVE: To determine the best treatment for children with recurrent infection
of the lower urinary tract and without anatomical abnormalities. METHODS: A
clinical study was conducted on 150 children (30 boys and 120 girls), aged 4 to
36 months (mean 16), with recurrent urinary tract infections (UTI) and no
radiological evidence of anatomical abnormalities. They were divided into three
groups: group I was treated with a single nightly prophylactic dose of an
antibiotic; group II received a single nightly dose of oxybutinin, or divided in
2-4 doses; group III received a single nightly prophylactic dose of an antibiotic
and oxybutinin as in group II. RESULTS: There were more episodes of UTI in group
I (44/50), more hospitalizations and problems of malnutrition, and a longer
period of treatment was required. In group II, 14/50 children had episodes of
UTI, their nutritional status improved and there were less hospitalizations. In
group III, 3/50 children had episodes of UTI; they were the best responders and
required a shorter duration of treatment. CONCLUSIONS: Prophylactic therapy
requires a longer period of treatment. The use of oxybutinin is an alternative
modality in the treatment of these children. Combination therapy with a single
nightly dose of an antibiotic and anticholinergic (oxybutinin) appears to be the
best therapeutic modality for children with recurrent UTI and no anatomical
abnormality.
PMID- 9656558
TI - [Double J ureteral catheter. Clinical complications].
AB - OBJECTIVE: To analyze the clinical complications of double-J ureteral catheters.
METHODS: The most relevant studies published in the literature since the self
retaining indwelling catheter was first described in 1967 are reviewed. RESULTS:
The experience and results reported in the most relevant studies are presented.
CONCLUSIONS: The double-J ureteral stent has become an integral part of the
urological armamentarium. It allows good urinary drainage from the kidney to the
bladder and is generally safe and well-tolerated. However, different
complications may occur with short- or long-term use of indwelling stents. These
complications vary from minor side effects such as hematuria, dysuria, frequency,
flank and suprapubic pain, to major complications such as vesico-ureteric reflux,
stent migration, encrustation, urinary infection, stent fracture, necrosis and
ureteral fistula. Most of these complications require removal of the catheter.
PMID- 9656559
TI - [Urologic iatrogenic disease].
AB - OBJECTIVE: The purpose of this paper is to emphasize that despite the undeniable
advantages of urological instrumentation (insertion of a ureteral catheter,
double-J catheter; percutaneous nephrostomy, etc.), it also carries some risks
and complications. METHODS: We report three cases of iatrogenic urological
complications due to use of endoscopic and percutaneous material.
RESULTS/CONCLUSION: Urologists, and particularly the residents, are reminded that
iatrogenic complications may occur even in the easiest and routine procedures of
the medical activity.
PMID- 9656560
TI - [Adrenal gland myelolipoma: review of the bibliography regarding a case].
AB - OBJECTIVE: To describe an additional case of this rare disease entity, with
special reference to its diagnosis and treatment, and to briefly review the
literature. METHODS: We report on an 82-year-old male with adrenal myelolipoma
that had been incidentally discovered during evaluation for another condition. A
left adrenalectomy was performed due to the large size of the tumor and in order
to determine its benign or malignant nature. RESULTS: The histopathological
findings disclosed an andrenal myelolipoma. CONCLUSIONS: Adrenal myelolipoma is
an uncommon tumor type. CT is the most effective diagnostic method. Surgery is
advocated in symptomatic cases and in asymptomatic cases with a large tumor mass.
PMID- 9656561
TI - [Condylomata acuminata in childhood: report of a case].
AB - OBJECTIVE: To report an additional case of condylomata acuminata in a child,
review the literature and discuss the medicolegal implications due to the
possibility of sexual abuse. METHODS/RESULTS: The diagnosis, treatment and
clinical course of the lesions are discussed. Psychological evaluation of the
child discarded infection by sexual transmission. CONCLUSION: Condylomata
acuminata in children represent a diagnostic difficulty due to the possibility of
infection by sexual transmission, although it should be taken into account that
non sexual transmission of this sexually transmissible disease is very frequent
in childhood.
PMID- 9656562
TI - [Pyelocaliceal urothelial carcinoma associated with pelvis lithiasis].
AB - OBJECTIVE: Epithelial neoplasms of the upper collecting system account for less
than 5 percent of all urothelial tumors and they are not histologically unlike
those of the bladder. We report a case of pelviocaliceal urothelial carcinoma
associated with a calculus in the renal pelvis. METHODS: A 75-year-old man who
presented with hematuria, fever and flank pain is described. The US and CT
findings disclosed a calculus in the left renal pelvis and hydronephrosis
nephrectomy was performed. RESULTS: The pathological analysis revealed a
pelviocaliceal urothelial carcinoma on an underlying stone and overexpression of
the p53 protein. CONCLUSION: Diagnostic imaging techniques may fail to detect
tumors of the renal pelvis with a large underlying stone. The overexpression of
the p53 protein may be involved in the malignant transformation of the urothelial
cells.
PMID- 9656563
TI - [Conservative treatment of microcytic carcinoma of the bladder; report of a new
case].
AB - OBJECTIVE: To report an additional case of small cell carcinoma treated
conservatively. METHODS: Herein we describe a case of small cell carcinoma of the
bladder that had been treated conservatively because of the age of the patient.
The specific characteristics of the case are described and the clinical and
pathological aspects of the disease are briefly reviewed. RESULTS/CONCLUSION:
Although treatment of this disease is primarily by cystectomy followed by chemo
and radiotherapy, organ-sparing neoadjuvant chemo and radiotherapy as an
alternative to surgery could be attempted to obtain complete remission in
selected patients.
PMID- 9656564
TI - [Extra-adrenal retroperitoneal paraganglioma].
AB - OBJECTIVE: To report a case of paraganglioma localized in the organ of
Zuckerkandl and to discuss its diagnosis, treatment and outcome. METHODS/RESULTS:
A 37-year-old female presented with a periumbilical mass and pain that radiated
to the lumbar region for the past three months. Abdominal US and CT disclosed a
well vascularized mass lying adjacent to the aorta, 1 cm from its bifurcation. At
laparotomy, an 8 x 10 cm tumor was discovered at the aortic bifurcation that
displaced the left ureter and included the inferior mesenteric artery.
Pathological analysis of the surgical specimen revealed a paraganglioma.
CONCLUSION: Extra-adrenal paraganglioma should be taken into account in the
differential diagnosis of retroperitoneal masses, particularly those adjoining
the abdominal aorta.
PMID- 9656565
TI - [Hematuria, dysuria, pollakiuria and general malaise, in a patient treated with
BCG instillations].
AB - OBJECTIVE: To report a case of granulomatous cystitis in a patient receiving
bacillus Calmette-Guerin intravesical therapy for urothelial carcinoma in situ.
METHODS: A 58-year-old man undergoing BCG intravesical therapy for urothelial
carcinoma in situ presented symptoms of intense cystitis. Cystoscopy was
performed and several bladder cold biopsies were obtained. RESULTS:
Histopathological analysis demonstrated epithelioid granulomas. CONCLUSION:
Cystitis arising from BCG therapy is defined as drug-induced or BCG-induced
cystitis. Intense cystitis and malaise are a serious complication since it is not
possible to distinguish patients with a simple uncomplicated local reaction from
those who will develop progressive systemic infection. Cystoscopy and biopsy can
be helpful in determining the nature of the condition and are recommended.
PMID- 9656566
TI - [Re: Testicular infarction, simulating a neoplasm].
PMID- 9656567
TI - The role of in vitro chemosensitivity tests to predict the clinical efficacy of
antineoplastic agents in genito-urinary tumors.
AB - OBJECTIVE: To develop an in vitro screening system to predict the response to
treatment of common malignancies of the genito-urinary tract. MATERIAL AND
METHODS: Flow cytometric analysis and cytotoxicity assays (trypan blue and lactic
dehydrogenase colorimetric tests) were performed on hormone resistant prostate
cancer cell line PC-3 and primary transitional cell carcinoma samples treated
with different antineoplastic agents and their combinations. Apoptosis induced by
different agents was also investigated by previously established criteria.
RESULTS: There were 9 bladder tumors (47.4%) in the study group that displayed
drug resistance to at least one antineoplastic agent. When the drugs were
examined individually, there was resistance to cis-platinum in 3 patients
(15.8%), methotrexate in 6 (31.6%), vinblastine in 7 (36.8%), epirubicin in 2 and
adriamycin in 2 patients (10.5%). Stratification of patients according to the
stage of the tumor revealed statistically significant difference between the
superficial and invasive tumors in terms of drug resistance (p < 0.05). In
prostate cancer cell line vinblastine treatment resulted in a significant
increase in S phase fraction. Percent cytotoxicity by trypan blue exclusion test
was 26.1% and was significantly higher than the control group (8.7%, p < 0.002).
Also, an increase in apoptotic index after the treatment was observed (44.4% and
12.1%, respectively; p < 0.0001). CONCLUSION: Both toxicity assays showed a very
good correlation (p < 0.005) and can be used to evaluate the effects of different
antineoplastic agents on individual tumors.
PMID- 9656568
TI - [Recent research for the development of anti-allergic agents--an approach for the
regulation of allergic functional molecule].
PMID- 9656569
TI - [Progress in cell biology on eosinophils].
PMID- 9656570
TI - [Analysis of inspiratory flow-volume curve].
AB - Inhaled antiasthmatic agents can be effective, but their efficacy depends on the
delivery system and on inhalation technique, especially in metered-dose inhalers
(MDI). To find out whether inhalation therapy for asthmatics had been performed
correctly, we studied inspiratory flow in the slow matter in healthy subjects and
bronchial asthma patients. About half of 30 patients studied inspired more than 1
L/sec inspiratory flow rate, especially in male. Inspiratory flow in the fast
matter (peak inspiratory flow; PIF) is important in the use of dry powder
inhaler, so we studied the correlationship between PIF and expiratory flow and
volume parameters. PIF correlated with PEFR, FEV1 and FEV1% in female, FVC and
%FVC in male, respectively. In summary, we must recognize slow inspiratory flow
can not be gotten easily, and asthmatic patients always have to use MDI carefully
in inspiratory flow. Some expiratory parameters of spirometry can accurately
predict PIF. The analysis of inspiratory flow-volume curve gives us beneficial
data in inhalation therapy.
PMID- 9656571
TI - [A new device for allergen skin testing].
AB - We have made a new device for allergen skin testing, which can be used easily. It
consists of two parts. One, several gears are fixed on a board in a row, and when
one gear goes round, other gears also go round simultaneously. A disposable
needle is attached to each gear. A semi-spherical hole is made in the lower
surface of a disposable needle, and a sharp needle is fixed in, but not at the
centre of the hole. The other, small tanks are arranged in a row at the same
distance as the gears. When the disposable needles are inserted to the tanks
filled with allergen extract, it is hold in a semi-spherical hole by surface
tension. The allergen extracts go intradermally, when the needles move semi
circular on a human skin. We performed skin tests to 23 patients with this
device, and got satisfactory results as screening tests.
PMID- 9656572
TI - [Isoproterenol continuous nebulization for childhood status asthmaticus. I.
Efficacy and side effects of high-dose method].
AB - We investigated the efficacy and the side effects of "high-dose isoproterenol
continuous nebulization" for childhood status asthmaticus. Subjects were 34
children who were hospitalized and underwent the nebulization therapy. The 50 ml
solution of 0.5% dl-isoproterenol was diluted in 500 ml of normal saline and
nebulized through an ultrasound nebulizer. The period of continuous nebulization
was 25.5 +/- 16.0 hours. The Wood's clinical score clearly decreased in 32 cases,
the average score changing from 7.7 +/- 0.8 to 2.9 +/- 1.3. Heart rate was
elevated significantly during the first 3 hours (156 +/- 25/min at the start of
the nebulization, 180 +/- 20/min at 1 hour, 171 +/- 23 at 3 hours), and then it
decreased gradually to 122 +/- 25/min at the cessation of the nebulization. Serum
GOT, LDH, CPK, and potassium were elevated after the nebulization compared with
the values before the treatment, though the changes were not statistically
significant. CPK-MB fraction after the nebulization was higher than normal range
in 12 of 13 subjects. Of 34 subjects, 11 (32%) complained nausea or vomited, 2
showed arrhythmia on ECG (ventricular premature conduction), 1 developed
myocardiac infarction, and 1 developed possible heart failure, some of which
might be attributable to the pharmacological side effects of isoproterenol
nebulization. We conclude that "high-dose isoproterenol continuous nebulization"
is an effective method for childhood status asthmaticus, but there is some risk
of serious side effects. This method was originally developed as a method
indicated for the case of respiratory failure or threatened respiratory failure
following status asthmaticus, and we should not extend the indication of this
method thoughness.
PMID- 9656573
TI - [Allergen-induced cytokine messenger RNA expression of peripheral blood
mononuclear cells in active and remission of food allergy].
AB - Substantial part of patients who suffer from food allergy outgrow their allergic
reaction. Moreover the mechanisms of this phenomenon are poorly understood. We
studied cytokine mRNA expression in peripheral blood mononuclear cells (PBMC)
from children with egg allergy, nine patients on active stage and eight were
outgrown, and four healthy controls, by use of reverse transcription polymerase
chain reaction. Following ovalbumin (OVA) stimulation in vitro, active patients
demonstrated increasing IL-5 mRNA. In comparison, no increasing expression of IL
5 mRNA was observed in outgrown and healthy children. IL-4 and IFN-gamma mRNA
expression has no tendency either to increase or to decrease in all three groups.
There was no difference of proliferative responses for OVA among these groups
suggesting that outgrown patients' PBMC did not fall into anergy or clonal
deletion. These data suggested the change in balance of cytokine production of
PBMC which were stimulated by allergen is a trigger for "outgrow" of food
allergy.
PMID- 9656574
TI - [Theophylline reduces serum levels of ECP in vitro].
AB - Measurement of serum levels of ECP has been widely used for monitoring airway
inflammation in bronchial asthma and recently been applied to measure anti
inflammatory effect of theophylline. However, reduced levels of ECP in
theophylline-administered patients may express not only in vivo effect of
theophylline but also in vitro effect after sampling because serum ECP measures
released ECP during coagulation and theophylline has been reported to inhibit
eosinophil degranulation in vitro. In order to answer the question, we tested
whether theophylline added to blood after sampling reduces measured levels of
serum ECP. Various concentrations of theophylline were added to SST tube, to
which venous blood from atopic patients was drawn. Serum was, then, obtained by
centrifugation after 15 min to 6 hours of incubation at room temperature.
Theophylline significantly reduced serum ECP in a concentration-dependent manner.
Percent reduction of ECP levels at 1 hour of incubation were 11.9%, 18.7%, 22.8%,
and 51.7% at theophylline levels of 5, 12.5, 22.5, and 120 micrograms/ml,
respectively. Kinetics of serum ECP release was also inhibited in the presence of
theophylline. These results suggest that in vitro effect of theophylline on serum
ECP levels should be considered when data of serum ECP in patients who take
theophylline are interpreted.
PMID- 9656575
TI - [Effects of institutional therapy and factors which influence the prognosis].
AB - We examined the effect of institutional therapy on asthmatic children and
evaluating the factors influencing the prognosis. We analyzed the questionnaires
and laboratory findings obtained form the 565 children who had been treated with
the therapy in National Higashi-Saitama Hospital from April 1978 to March 1997.
The institutional therapy seems to be effective in the following 3 aspects. 1)
Pulmonary function test such as FEV1.0, and bronchial hypersensitivity test such
as acetylcholine inhalation test were improved. 2) Exercise abilities such as
free running were improved. 3) More than 40% of the patients had no asthma attack
or only a few mild asthma attacks requiring no medication. When compared the
group whose symptoms were not improved with the remission group, who had no
asthma attack, significant differences were seen in the following points, 1) The
dose and the number of the medicines at the end of the hospitalization, 2) the
bronchial hypersensitivity test, 3) the age of onset, 4) the age of the symptoms
become perennial and 5) the term from the symptoms become perennial to the
hospitalization were significantly different. The therapy principles including
the recipes for exercise training were not different between the two groups. It
is concluded that we should consider institutional therapy or, a combination of
physical training and environmental control as one of the most important
therepeutic methods when asthmatic symptoms become perennial in spite of the
conventional medication.
PMID- 9656576
TI - [BCG-induced T cell anergy and its activation by IL-4].
AB - In response to stimulation with immobilized anti-CD3 antibody, splenocytes from
C57BL/6 and BALB/c mice principally produced INF-gamma and IL-4, respectively.
However, both splenocytes equally proliferated in response to ConA. We compared
the changes after inoculation with BCG (1 mg/mouse) in their capacity to produce
IL-4 or IFN-gamma in response to anti-CD3 antibody and to proliferate in response
to ConA. Splenocytes from C57BL/6 and BALB/c mice, that had been inoculated with
BCG 4 weeks before, produced IFN-gamma with diminished IL-4 production in
response to anti-CD3 antibody. Furthermore these splenocytes became anergic to
ConA stimulation and died due to cell apoptosis in stead of proliferation.
However, we observed the strain difference at 12 weeks after BCG-infection. BCG
primed C57BL/6 splenocytes, that continuously produced IFN-gamma in response to
anti-CD3 antibody, failed to proliferate in response to ConA. In contrast, BCG
primed BALB/c splenocytes, that increased IL-4 production but decreased IFN-gamma
production when stimulated with anti-CD3 antibody, could proliferate well in
response to ConA. Since the splenocytes of BALB/c mice became ConA responsive
along with their shifting from Th1 dominant immune response at 4 weeks to Th2
dominant immune response at 12 weeks after BCG-inoculation, IL-4 was assumed to
play a crucial role in activation of anergic T cells. Therefore, we stimulated
splenocytes from both strains of mice infected with BCG 4 weeks before with ConA
in the presence or absence of IL-4. Splenocytes from BCG-infected BALB/c mice
showed marked proliferation, while those from BCG-infected C57BL/6 mice failed.
We found that IL-4 protected against ConA-induced cell apoptosis in BALB/c
splenocytes but not C57BL/6 splenocytes.
PMID- 9656578
TI - [Bioethics in primary care: questions of confidentiality].
PMID- 9656577
TI - [A comparison of a 3 day course with a 2 week course of oral prednisolone in
patients with chronic asthma].
AB - To investigate an appropriate duration of short course of a oral prednisolone
(PSL), we compare the results of a 3 day course of PSL (3D) with those of a 2
week course of PSL (2W) in 20 patients with chronic asthma. All subjects had been
inhaling beclomethasone dipropionate (BDP, mean daily dose: 1325 micrograms), and
had been self-monitoring their peak expiratory flow rate (PEF) for at least 6
months. Mean +/- SE of the best PSL-induced PEF in 2W (2W-best) was not different
from that in 3D (397 +/- 29 and 356 +/- 23 L/min, respectively, p = 0.26). Mean
weekly morning PEF/2W-best before and 1, 2, 3 and 4 weeks after PSL was 60, 76,
80, 76 and 76% in 2W, and 63, 73, 67, 67 and 65% in 3D, respectively. Both
changes over the course of time were significant. The frequency of emergency room
visits and/or unscheduled hospital visits was not significantly different between
2W and 3D. However, both the frequency of use of inhaled beta 2 agonists and the
symptom score significantly decreased only in 2W. Seven patients (35%) did not
need additional oral PSL during the 4-week period after initiating 3D, and among
these patients, emergency room visits and/or unscheduled hospital visits were
completely controlled. In conclusion, although the effect of 3D was inferior than
that of 2W, it was a sufficient duration in 35% of the patients, and thus, may be
appropriate as a initial duration of rescue course of oral steroids.
PMID- 9656579
TI - [Factors involved in the non-compliance of the pharmacologic treatment of
dyslipidemia].
AB - OBJECTIVES: To find how much non-compliance with lipid-lowering drug treatment
there is, its causes and to describe the profile of non-compliant patients.
DESIGN: Prospective study. SETTING: Primary Care Centres in the province of
Alicante. PATIENTS: 107 patients under drugs treatment for lipaemic disorders and
belonging to live General Medical practices. MEASUREMENTS AND MAIN RESULTS: To
evaluate compliance, the method of a surprise count of pills in the patient's
home was used. Compliant patients were defined as those with between 80 and 110%
compliance. 46.7% were non-compliant (C.I. 37.3-56.2), with 42% under-compliant
and 4.7% over. Forgetfulness and unawareness accounted for 68% of the reasons for
non-compliance. Associated factors were: moderate to high cardiovascular risk (p
= 0.03), stating that the drug treatment was followed badly (p = 0.01), less than
a year in regular treatment (p = 0.006), monitoring lipaemia poorly (p = 0.003).
CONCLUSIONS: Non-compliance with pharmacological treatment in patients with
lipaemia is high. Its causes are known, as are several factors associated to non
compliance which could be used to identify the non-complier.
PMID- 9656580
TI - [The chronically ill at home and the impact in main caregivers].
AB - OBJECTIVE: To analyse the repercussions that caring for chronically sick patients
at home can have on the health of the main carers. DESIGN: A descriptive
crossover study. SETTING: "Raval Nord" Health District, Barcelona. PATIENTS AND
OTHER PARTICIPANTS: All the 336 chronically sick at home recorded in the home
care programme during January to March 1996. All the 236 carers identified during
the same period. MEASUREMENTS AND MAIN RESULTS: 75% of the patients and 72% of
those considered the main carers answered a home questionnaire. Most of the
chronically ill at home were women (67%), with an average age of 81 (SD, 11). 18%
presented severe disorders in the Short Portable Mental Status Questionnaire
(SPMSQ), test which showed a significant relationship (p < 0.0001) with less
autonomy according to the Katz index. 36% of carers remarked physical problems
such as repeated back-aches and lumbago. CONCLUSIONS: The most important
disorders affecting the autonomy and mental health of chronic patients at home
lead to increased psychological malaise in the career, especially if he/she is a
family member.
PMID- 9656581
TI - [Frequency, characteristics and consequences of falls in a cohort of
institutionalized elderly patients].
AB - OBJECTIVE: Falls in the elderly are a major problem because of their high
morbility and mortality rates and health expenditures. However, there are few
studies about this problem in our country. The purpose of the present study was
to know the frequency, features and consequences of falling among
institutionalized elders. METHODS: We carried out a prospective cohort study
using a sample of 190 persons aged 65 years and older living in two nursing
homes. All subjects underwent a comprehensive evaluation at the onset of the
study. During a mean follow-up period of 310 days, all falls were recorded.
RESULTS: There were a total of 121 falls in 72 (37.9%) subjects, twenty five of
whom (34.7%) experienced two or more falls. The fall incidence per person-year
was 0.75. As compared with males, females had a density ratio (DR) of 2 (1.2-3.2;
95% confidence interval-CI). Falling was more frequent in the bedrooms and living
rooms (43.8%). DISCUSSION: This results agree with others studies about the high
fall incidence in the elderly and bring out new features about circumstances and
consequences of falls.
PMID- 9656582
TI - [Effect of the presentation of results from clinical trials on the intention to
prescribing: relativity of the relative risk].
AB - OBJECTIVE: To determine if the methods of reporting results of clinical trials
affects the physician views on prescribing. DESIGN: Analysis of responses, from a
convenience sample of primary care physicians, of one teaching exercise on
prescribing intention which showed 5 different methods of reporting results:
relative risk reduction (RRR), absolute risk reduction, the percent of event free
patients, the number needed to treat (NNT) and RRR and mortality. SETTING: Curses
of clinical management in Valencia and Barcelona. RESULTS: The willingness to
prescribe was significantly influenced by the way in which data were presented,
being major when they were showed as RRR and minor when mortality was added.
CONCLUSIONS: The method of reporting trial results has an important influence on
the prescribing intention. The reporting of clinical trial results, and their
abstracts or citations, should be include the NNT and negative results, for
avoiding a subjective bias of treatment effect magnification.
PMID- 9656583
TI - [Antibiotic consumption (1993-1996) in primary care in a health area with a high
rate of bacterial resistance].
AB - OBJECTIVE: To analyse the consumption of antibiotics and the consumption trend
for 1993 to 1996 in Primary Care in a health area with high rates of bacterial
resistance. DESIGN: Comparative retrospective analysis. SETTING: Costa de Ponent
Primary Care area, with a census of 1,158,098 inhabitants. PATIENTS: Those
belonging to the health area who took antibiotics during the study period.
INTERVENTIONS: Data were obtained from the records of the Catalan Health Service.
As a measurement of consumption of various antibiotics, the daily defined dose
(DDD)/1000 inhabitants/day (DID). RESULTS: The DID total was very high, 17,048, a
light increase from 1993 to 1996 (+2.4%). The groups which increased were
cephalosporins by 42.8% and macrolides by 12.2%. CONCLUSIONS: The total
consumption of antibiotics was very high and consonant with the high rate of
bacterial resistance detected in our area in recent years. The progressive
consumption of the most recently introduced antibiotics was not accompanied by a
proportionate decrease in the consumption of others. The rationalisation of
antibiotic use and the formation of Antibiotic Policy Committees in the Primary
Care field should be a priority public health objective.
PMID- 9656584
TI - [Follow up programs for children in primary care: failures to keep the
appointments].
PMID- 9656585
TI - [Assessment of an interventional study on iodine deficiency in Burkina Faso, 1990
1993. Direction de la Sante de la Famille (Burkina Faso)].
AB - OBJECTIVES: To find how the urinary parameters of iodine excretion evolved in a
community with deficiencies, after administering iodine orally and IM in two
provinces in Burkina Faso; to recommend a national strategy to tackle iodine
deficits. Design. A longitudinal survey before and after the iodine was given (12
months). Descriptive analysis of the data. SETTING: Provinces of Namentenga and
Passore in Burkina Faso. PARTICIPANTS: The general population of the two
provinces who satisfied age-sex criteria: males from 0 to 25, females from 0-45.
Randomised two-stage sampling. 423 people in all took part (210 in Namentenga and
213 in Passore). INTERVENTIONS: The administration of 1 ml of iodised oil
(Lipiodol) orally in Namentenga and IM in Passore. MEASUREMENTS AND MAIN RESULTS:
The urinary parameters of micrograms of iodine per gr. of Creatinine, and
micrograms of iodine per dl of urine, were used. Figures for normalisation of the
urinary parameters 12 months after iodisation was significantly higher in Passore
province, where iodine was administered IM. CONCLUSIONS: The intramuscular
pathway has more longlasting effects, but the characteristics of Burkina Faso's
health system and the feasibility of a medium or long-term intervention make it
advisable that iodine supplements be administered orally.
PMID- 9656586
TI - [Sexual harassment: assessment and follow-up].
PMID- 9656587
TI - [Consensus document on the detection and treatment guidelines for diabetic
nephropathy in Spain. Spanish Societies of Diabetes, Endocrinology, Family and
Community Medicine, and Nephrology].
PMID- 9656588
TI - [Generic pharmaceutical specialties: bioequivalent and interchangeable
medications].
PMID- 9656589
TI - [Self-management in primary care. Working Group semFYC-SEMERGEN 1996].
PMID- 9656590
TI - [Bureaucratic activity in the consultation of the primary care physician.
Proposals for a debureaucratization. Working Group semFYC-SEMERGEN 1996].
PMID- 9656591
TI - [Anticoagulation/antiaggregation treatment in patients with non-rheumatoid atrial
fibrillation].
PMID- 9656592
TI - [Anticoagulation in atrial fibrillation: implications in primary care].
PMID- 9656593
TI - [Postcoital treatment in primary care].
PMID- 9656594
TI - [Vaccination against A-C meningococcal meningitis: ethics and management].
PMID- 9656595
TI - [The place of surgery in the treatment of locally advanced rectal cancer].
AB - We considered as local advanced rectal cancer (LARC) tumours invading the serosa
or adherent to neighbouring organs, tumoral fistulas, histopathologically proved
invasion of regional lymph nodes, peritoneal carcinomatosis with or without
neoplastic ascites. Out of 146 rectal cancers submitted to surgery between 1984
1996, 47 had LARC (19 man and 28 women aged of 19 to 88 years) developed in the
inferior 2/3 of rectum. We performed in these cases 11 Miles operations, 12
posterior pelvectomies, 3 Dixon resections, 16 colostomies and 5 exploratory
laparotomies. To these were associated 4 partial cystectomies, 4 anexectomies, 4
partial enterectomies and 2 excisions of hepatic metastasis. In 27 patients
adjuvant or neoadjuvant therapy was associated. We registered 3 deaths, 6
parietal infections and 1 stercoral fistula. Postoperative survival was 3-6
months for 12 patients, 6-12 months for 13 patients, 1-2 years for 6 patients.
After the complex treatment 6 patients were alive at 5 years. Surgery is the
essential therapeutic act of LARC. Chemo/radiotherapy association increases the
survival, but not significantly.
PMID- 9656596
TI - [Repeat hepatic resections].
AB - Five cases of iterative liver resections are presented, out of a total of 150
hepatectomies performed between 1.01.1995-1.01.1998. The resections were carried
out for recurrent adenoma (one case), cholangiocarcinoma (two cases),
hepatocellular carcinoma (one case), colo-rectal cancer metastasis (one case).
Only cases with at least one major hepatic resection were included. Re-resections
were more difficult than the primary resection due, first of all, to the modified
vascular anatomy. Intraoperative ultrasound permitted localization of
intrahepatic recurrences. Iterative liver resection appears to be the best
therapeutical choice for patients with recurrent liver tumors.
PMID- 9656597
TI - [Late histopathological changes at the level of the residual pancreatic stump
after cephalic duodenopancreatectomy].
AB - In this paper the authors present a histopathological study concerning the
restant pancreas after cephalic duodenopancreatectomy for 3 cases that had a
lethal outcome. In this 3 cases was performed hte cephalic duodenopancreatectomy
with Child montage. This study showed that at the level of the restant pancreas
it develops a progressive atrophy of the exocrine pancreatic tissue.
PMID- 9656598
TI - [Intraoperative exploratory endoscopy in surgery of the digestive tract].
AB - The intraoperative endoscopy as a way of the range of the surgical exploration of
the abdomen is a valuable procedure combining surgical and endoscopical
maneuvers. It proved useful in following conditions: A. delicate surgical
approach of the anatomical segment; B. equivocal findings of the conventional
endoscopy; C. as a way of achieving therapeutical goals. In 56% of the cases a
transperitoneal approach was used and in the rest of the cases a conventional
technique. Sterilization was performed using glutaldehide 2%, 20 minutes before
the intervention. The methods was used in 50 cases, concerning reinterventions,
as well as primary diseases of unclear origin. Some were high-risk patients.
Therapeutically benefit was proven in all cases.
PMID- 9656599
TI - [A ureteral endoscopic approach--a minimally invasive method complementary to
nephroureterectomy].
AB - Nephroureterectomy with ureteral stump excision and perimeatal cystectomy is the
"golden standard surgical approach" for urothelial upper urinary tract cancer.
Nephroureterectomy is also necessary in renoureteral tuberculosis, with
compromised renal unit. Since June 1995 we performed the endoscopic distal
ureteral approach in 11 cases (9 cases with upper urinary tract cancer and 2
cases with renal tuberculosis and concomitant ureteral distal lesions). In 7
cases we performed ureteral stripping after nephrectomy and in 4 cases we
performed endoscopic disconnection of the intramural ureter followed by
nephroureterectomy (in one operative step). Ureteral stripping was realized in
two ways: perimeatal resection of the ureter and 12 o'clock incision. There was
only one intraoperative complication which consisted in the dislodgement of the
ureteral catheter who needs conversion to open surgery. Mean follow-up period was
12 months (range 2 to 28). The evolution of the patients was satisfactory, with
significant reduction of the hospitalization. According to our experience the
endoscopic distal ureteral approach is a safer complementary proceeding to the
one step nephroureterectomy, being performed faster and easier than open
ureterectomy.
PMID- 9656600
TI - [Antroduodenoplasty (an original method) in the surgical treatment of a
perforated duodenal ulcer].
AB - It's present an original method in the treatment of perforated duodenal ulcer
(antro-duodenoplasty or antro duodenal aposition). To a group of 256 patients
with gastro-duodenal ulcer operated in the period 1985-1995, it is fancy an apply
these method to 56 patients (21%). These method applied is simple and performed
in any surgical service and it't not necessary a special technical organization.
The evolution of 56 patients there is no incidents. The originality consist in
your simplicity, but and in the fact that these method it's not communicated in
the surgical literature of Romania or anywhere in the latest ten years.
PMID- 9656601
TI - [Liver transplantation. II.A rapid technic for taking a liver graft in the
context of taking multiple organs from a donor in a state of brain death].
PMID- 9656602
TI - [Nosocomial infections in the Clinica Chirurgie CFR, Craiova].
AB - The authors present Craiova CFR General Surgery Clinic experience on hospital
infections from 1991 through 1996. This study shows that the frequency of
hospital infections in our clinic is greater than all the other postoperative
complications. Over the investigated period of time we witnessed an increase in
the incidence of the postoperative septic complications in addition to those
directly linked to the operated interventions (e.g. wound infections,
postoperative peritonitis) such as: pulmonary infections: urinary tract
infections, catheter sepsis etc. Finally, the authors pointed to the consequences
of the hospital infections such as: mortality and late morbidity rates, economic
implications. Thus, it is worth mentioning that 30 deaths (75%) out of our clinic
total of 40 over the studied period of time were due to a postoperative
infections and treatments.
PMID- 9656603
TI - ["Combined treatment" in the liver metastases of colorectal cancer].
AB - Patients with liver metastasis after colo-rectal cancers are, from the point of
une of their disease evolution in the final stadium (the IV th. stadium). Hence,
we consider the attempt for liver metastasis treatment, as being desperate
experiments to extend the patient's life, taking high risks and having chances of
immediate failure. Since 1995 me've started a study about patients operated for
colo-rectal cancers that will stand transarterial chemoembolization of their
hepatic metastasis, 2-4 weeks before the surgical intervention for hepatectomy.
We expose 17 cases to which we performed such a combined therapy, between 1995
1997. We had to postoperative death after major hepatectomies. The other patients
are survived by our clinics.
PMID- 9656604
TI - Normative data for a brief neuropsychological battery administered to English-
and Spanish-speaking community-dwelling elders.
AB - The use of neuropsychological tests in non-English-speaking populations and among
those with less education has been limited because most tests have been
standardized for English-speaking populations with relatively high levels of
education. In effort to establish norms, a battery of neuropsychological tests
was administered, in either English or Spanish, to 995 normal elders with a wide
range of educational attainment, residing in the community of Washington Heights
Inwood in northern Manhattan. Results indicate that age, education, and language
all influence test performance and should be considered when evaluating
neuropsychological measures.
PMID- 9656605
TI - Verbal learning and memory in alcohol abusers and polysubstance abusers with
concurrent alcohol abuse.
AB - To define the combined effects of drug and alcohol abuse on verbal learning and
memory, 70 alcoholic and 80 polysubstance abuse (PSA) individuals with concurrent
alcohol abuse were compared on a list learning task, the California Verbal
Learning Test (CVLT). Despite demonstrating similar learning strategies, response
styles, and error patterns, the PSA group nontheless exhibited significantly
greater recall deficits than the alcoholic group on the CVLT. These deficits were
particularly evident in those who were heaviest abusers of cocaine. PSA
participants did not, however, evidence greater recognition memory deficits. This
pattern of greater deficits on recall than on recognition memory, as well as poor
consolidation, is consistent with the initiation-retrieval difficulties of
patient groups with subcortical dysfunction. It is concluded that the combined
use of alcohol and drugs, cocaine in particular, may compound memory difficulties
beyond what is typically observed in alcoholic individuals.
PMID- 9656606
TI - Information processing and antiretroviral therapy in HIV-1 infection.
AB - Computerized reaction time (RT) tasks are sensitive measures of subclinical HIV
related mental slowing. We previously reported that nondemented HIV-seropositive
patients on antiretroviral therapy at the time of testing had faster choice RTs
compared to matched untreated seropositive participants. In the present study, we
evaluated the performance of 163 nondemented HIV-seropositive participants on a
reaction time version of the Stroop task as a function of antiretroviral status.
Persons on antiretroviral therapy at the time of testing had significantly faster
reaction times than untreated individuals, although treated asymptomatic
participants showed significantly less Stroop interference than treated
symptomatic participants. These effects could not be attributed to differences in
demographic variables, disease status, substance abuse, or psychological
distress. These data indicate that central information processing is faster for
patients treated with antiretroviral compounds compared to untreated patients,
and suggest that reaction time tasks may have significant potential utility in
clinical trials of neuroprotective compounds.
PMID- 9656607
TI - Long-lived picture priming in normal elderly persons and demented patients.
AB - Normal elderly control participants showed short-term (10-min delay) and long
term (12 months delay) priming on the Gollin Figures Test. Nearly all patients
with Alzheimer's disease or vascular dementia showed short-term priming, but the
magnitude of their priming was less than that of controls. Significant long-term
priming was not observed for the dementia groups. Differences between controls
and dementia patients on the short-term priming test may depend upon structural
perceptual processes that are intact in dementia patients and controls and
explicit memory functions available only to controls. The same model could
account for differences between normal elderly and dementia patients on the long
term priming test, but several other explanations are also plausible.
PMID- 9656608
TI - Comparative effects of schizophrenia and temporal lobe epilepsy on memory.
AB - The goal of this study was to further characterize episodic memory functioning in
schizophrenia. This study compared verbal and visual learning and memory
performance in (1) patients with schizophrenia (N = 35), (2) patients with
temporal lobe epilepsy (TLE; N = 30), and (3) normal controls (N = 25). Results
indicated significant memory impairments in patients with schizophrenia and TLE.
"Savings" score measures of memory decay showed that the loss of information in
schizophrenia and TLE was approximately equal, and quantitatively mild compared
to that found in most neurologic groups with memory disorders. The severe
difficulty shown by the schizophrenia group on a task of incidental recall
suggested that the absence of instructional set added to a vulnerability to
memory deficit. In contrast, relatively mildly impaired performance on paired
associate learning suggested that patients with schizophrenia benefited from
retrieval cues, multiple trials, and short (nonsupraspan) informational loads.
Because patients with schizophrenia consisted of a relatively nonchronic sample
with a mean IQ of 99.7, their memory disorder could not be attributed to
schizophrenic dementia, nor was it accounted for by other potential confounds.
Patients with schizophrenia, even those relatively early in the course of
illness, have a mild episodic memory disorder.
PMID- 9656609
TI - A comparison of clustering solutions for cognitive heterogeneity in
schizophrenia.
AB - A cluster analytic solution based upon a battery of tests consisting of the
Halstead Category and Tactual Performance Tests, the Trail Making Test, and the
Wisconsin Card Sorting Test was compared with a solution based on the subtests of
the Wechsler intelligence scales, utilizing a sample of 221 schizophrenic
patients. Both analyses permitted four-cluster solutions, and we found a weak but
significant degree of association between solutions. Examination of external
validity of the two solutions revealed stronger associations with clinical
variables for the Wechsler-scale-based solution. The major conclusions were that
the existence of cognitive heterogeneity in schizophrenia exists across a broad
range of abilities, and appears to reflect a combination of continuity of ability
level and existence of possible subtypes requiring further neuropsychological and
neurobiological verification.
PMID- 9656610
TI - Neuropsychological comparisons of Spanish-speaking participants from the U.S.
Mexico border region versus Spain.
AB - Two samples of participants from the U.S.-Mexico Borderland (N = 185) versus
Spain (N = 205) were compared on 16 Spanish-language neuropsychological measures.
In most measures the two samples obtained similar results. There were some
significant main effects of place of birth and some significant interactions
between education and place of birth. Differences between the samples diminished
with increasing levels of education. Within the Borderland sample, percent of
life span spent in the U.S. and bilingual status were correlated with performance
in some tests. Increased percent of life span spent in the U.S. was negatively
correlated with performance on a Spanish word-generation task, and positively
correlated with performance on the Wisconsin Card Sorting Test. Bilingual
Borderland participants performed significantly better than monolingual speakers
in learning a list of words. We suggest that the most likely causes for the
observed interaction effects are documented regional differences in early SES
related nutrition, medical care, quality of educational experiences, and general
socioeconomic conditions.
PMID- 9656611
TI - Characteristics of impaired awareness after traumatic brain injury.
AB - Impaired awareness of the effects of brain injury is a commonly observed and
poorly understood finding in traumatic brain injury survivors. Nonetheless,
impaired awareness has been identified as a major factor in determining outcome
for traumatic brain injury survivors. Review of previous studies of impaired
awareness in this patient population revealed a number of preliminary findings
regarding the nature of this phenomenon. The present paper presents the results
of 2 new studies with a total of 111 traumatic brain injury patients conducted to
bring further clarity to this area. Findings confirmed and extended many results
of previous investigations. Specific findings included patient overestimation of
functioning as compared to family member ratings, patient report of greater
physical than nonphysical impairment, greater patient-family agreement on
specific ratings of patient functioning than on general ratings, greater
agreement of family and clinician ratings of patient functioning with each other
than with patient self-ratings, and partial disagreement of different methods of
measuring impaired awareness.
PMID- 9656612
TI - Primary progressive semantic aphasia: a case study.
AB - A longitudinal case study of a patient with a progressive loss of meaning of
objects with preserved phonology and syntax is presented. Repeated measures of
language, praxis, visual cognition, and semantic processing were carried out. The
patient still has preserved conversational speech, social skills, and orientation
in her 8th year of her illness, but shows severe anomia and comprehension deficit
in all modalities of stimulus presentation. In addition to standardized tests of
language, cognition, and memory, specific experiments of categorization,
modalities of word access, item consistency, category specificity, and definition
of words were carried out. Results indicate a frequency dependent loss of meaning
that was consistent in all modalities and throughout all object categories.
However, the relative preservation of visual categorization of all categories
tested and the language based categorization of animals suggested some
fractionation of semantic memory. Relative preservation of autobiographical and
personal memories versus semantic memory was a striking observation. Evidence for
selective impairment of central semantic processing was obtained from experiments
indicating item consistency of loss and the lack of semantic cuing. Neuroimaging
evidence of left temporal lobe atrophy and the classical picture is compatible
with similar cases published under the term semantic dementia or "transcortical
sensory aphasia with visual agnosia" and suggest the diagnosis of Pick's disease.
PMID- 9656613
TI - External cueing systems in the rehabilitation of executive impairments of action.
AB - The use of a mnemonic cueing system (NeuroPage) and a paper and pencil checklist
in the rehabilitation of executive problems in a 50-year-old woman are described.
Following a CVA 7 years earlier, the patient, despite intact general intellectual
and memory functioning, had specific executive impairments of attention,
planning, realizing intended actions, and also exhibited behavioral routines
similar in form to obsessive-compulsive rituals. In a series of ABAB single-case
experimental designs, the efficacy of 2 external cueing systems in prompting
appropriately timed action is demonstrated. It is argued that the combination of
external control and increased sustained attention to action were critical to the
success of NeuroPage with this patient. Furthermore it is hypothesized that the
checklist was effective in facilitating the patient's ability to foresee and
recognize the consequences of her actions, which in turn had an impact on the
probability of her changing those same actions.
PMID- 9656614
TI - Addressing a continuum of recovery after acquired brain injury.
PMID- 9656615
TI - "A golden decade" for kidney medicine. Gene therapy is expected to result in a
new break through.
PMID- 9656616
TI - [A currently developed method of measurement. A discovery of specific nerve
fibers explains the way of itching through the body].
PMID- 9656617
TI - [Positive results after open thoracic surgery among the elderly].
PMID- 9656618
TI - [Confusing guidelines for psychotherapy].
PMID- 9656619
TI - [We appeal for the change of the circumcision rite].
PMID- 9656620
TI - [Double messages to persons with problems due to amalgam and computer screens].
PMID- 9656621
TI - [More stringent directives are necessary when it comes to non-prescription
drugs].
PMID- 9656622
TI - [Klinefelter syndrome affects mostly boys. An underdiagnosed chromosome
abnormality].
AB - Although Klinefelter's syndrome is the most common sex chromosome anomaly,
affecting one in 5-800 boys, our knowledge of the syndrome is still poor. This is
reflected in the paucity of published literature as compared, for example, with
the vastly greater number of publications on Turner's syndrome with its lower
incidence of 1/2,500 girls. Klinefelter's syndrome is manifestly underdiagnosed.
Existing knowledge mainly derives from cases characterised by prominent
symptomatology. Early diagnosis is important if additional support and resources
are to be made available to the patient and his family. Testosterone replacement
therapy should be initiated as soon as clinical and laboratory evidence becomes
available. In selected cases, testosterone treatment can be started already
during adolescence. At present, there is no established treatment for the
infertility which almost always accompanies the condition.
PMID- 9656623
TI - [Ticks--a medical topic of current interest which sticks].
PMID- 9656624
TI - [Good results of concentration on the care of heart failure in Malmo. Emergency
admissions to hospital were reduced by 24 per cent].
PMID- 9656625
TI - [National psychiatric guidelines compiled].
PMID- 9656626
TI - [A forgotten fraudulent bean--a case of favism. Fava bean may cause life
threatening hemolysis in predisposed persons].
PMID- 9656627
TI - [Reduced drug costs with the reference cost system].
PMID- 9656628
TI - [Three cases of nerve injury in connection with orthopedic laparoscopic surgery].
PMID- 9656629
TI - [A conflict between physicians and nurses about the drug lists. Please, do not
disturb--the drug documentation is going on].
PMID- 9656630
TI - [Better and cheaper care in heart failure. Efficient care programs save
resources].
PMID- 9656631
TI - [A new series: coronary vessels. Good strategy saves more patients with acute
coronary syndrome].
PMID- 9656632
TI - [Unbiased neutral handling is wanted for the inspection of hospital departments].
PMID- 9656633
TI - [Occupational environment of interns may be improved with the help of special
ombudsmen].
PMID- 9656634
TI - [Insinuating negative quotation on veterinary medicine].
PMID- 9656635
TI - [On the blessings of acupuncture].
PMID- 9656636
TI - [Emergency coronary care--successful, but unequaly distributed].
AB - The need of acute coronary care is increasing because of an increase in the
incidence of severe angina pectoris, and despite a reduction in that of acute
myocardial infarction. Patients with acute myocardial infarction are
characterised by continuously increasing age, lower mortality, and shorter
hospitalisation. The improvement in acute care is related to increased use of
expensive drugs, new diagnostic methods, and an increasing coronary
revascularisation rate. However, there is still inequality in the utilisation of
cardiac care, and in order to further enhance its quality and equality of
utilisation, there is an emphatic need of common registries.
PMID- 9656637
TI - [The man behind Paget's syndrome. He gave name to diseases of the skeleton,
breast and vulva].
PMID- 9656638
TI - [Pharmacological pain analysis as diagnostic and therapeutic help].
PMID- 9656639
TI - [Heart failure is expensive! Correct drug utilization can reduce the number of of
expensive days in hospital].
PMID- 9656640
TI - [New drugs against insulin resistance].
AB - Insulin resistance is an important mechanism in the development of the insulin
resistance syndrome and type 2 diabetes. Although treatment has hitherto been
confined to metformin or non-pharmacological measures, efforts are now being made
to discover new drugs active against insulin resistance, so-called insulin
sensitisers, for instance among the thiazolidinedione group. These are beginning
to be tested in larger clinical trials where they have manifested effects not
only on glucose metabolism but also on other cardiovascular risk factors such as
hyperlipidaemia, defective fibrinolysis, and hypertension. However, adverse
reactions to one of these drugs, troglitazone, include severe hepatic effects in
certain cases. Accordingly, registration of the product has been stopped for use
in Europe, but not in the USA and Japan. It is likely to take some time before
thiazolidinediones will be introduced for clinical use in this country, though
research and development continue.
PMID- 9656641
TI - [Postoperative laryngospasm may induce pulmonary edema. An unusual or overlooked
complication?].
AB - Young and healthy patients in whom laryngospasm secondary to postoperative
extubation is encountered run a risk of developing pulmonary edema. The mechanism
behind the edema is thought to be a strongly negative intrathoracic pressure
generated by the patient's forced inspiration against a closed glottis. A net
flow of fluid occurs to the interstitial space and further to the alveoli.
Unusually the pulmonary edema can be noticed within a few minutes after relief of
the obstruction, but occasionally it is delayed for several hours. The condition
is potentially life-threatening, but usually responds favourably to positive
pressure ventilation and diuretics. In anaesthesia and intensive care, it is
important to be aware of the complication in order to be ready for adequate
therapy when needed. We present three cases from the Central Hospital in Vaxjo,
where pulmonary edema occurred directly following postoperative extubation.
PMID- 9656642
TI - [Surgery and/or talk. Dialogue is as important as diagnosis-based measures].
PMID- 9656643
TI - [Tooth injuries in connection with intubation anesthesia: severity of the disease
and dental status].
PMID- 9656644
TI - [The king of Bavaria, creator of the fabulous castle, killed his psychiatrist].
PMID- 9656645
TI - Estimation of variance components based on diallel model.
AB - The problem of estimation of variance components based on diallel model for
unbalanced data has been addressed. The least squares approach to quadratic
estimation has been adopted in obtaining the explicit solutions for the design
and genetic components of variance.
PMID- 9656646
TI - Some perspectives on modeling leukemia.
AB - A diffusion model of leukemia is presented. The space-occupying effects of
leukemic cells during leukemic expansion is investigated. The analyses and
simulations of the model suggest that acute leukemia is a state in which
positions inhabited by colonies of normal cells are invaded by emerging colonies
of abnormal cells. Normal cells are then driven to a state of extinction as
leukemic cells evolve toward high and dominant steady state levels.
PMID- 9656647
TI - Analysis of a dengue disease transmission model.
AB - A model for the transmission of dengue fever in a constant human population and
variable vector population is discussed. A complete global analysis is given,
which uses the results of the theory of competitive systems and stability of
periodic orbits, to establish the global stability of the endemic equilibrium.
The control measures of the vector population are discussed in terms of the
threshold condition, which governs the existence and stability of the endemic
equilibrium.
PMID- 9656648
TI - The deterministic limit of infectious disease models with dynamic partners.
AB - This paper analyzes the large population dynamics of an infectious disease model
with contacts that occur during partnerships. The model allows for concurrent
partnerships following a very broad class of dynamic laws. Previous work, with a
stochastic version of the model, computed the reproductive number, the initial
growth rate, and the final size. In the present paper, the deterministic system
that is the limit for large populations is constructed. The construction is
unusual in requiring two different scaling factors. Next, the approximation used
by Watts and May for a related model is compared with the exact solution. This
approximation is most accurate at the beginning of the epidemic and when
partnerships are short. Lastly, the model is generalized to allow dependencies
among partnerships. This generalization permits proportional mixing with an
arbitrary distribution on the number of partners.
PMID- 9656649
TI - Existence and uniqueness of endemic states for the age-structured S-I-R epidemic
model.
AB - The existence and uniqueness of positive steady states for the age structured S-I
R epidemic model with intercohort transmission is considered. Threshold results
for the existence of endemic states are established for most cases. Uniqueness is
shown in each case. Threshold used are explicitly computable in terms of
demographic and epidemiological parameters of the model.
PMID- 9656650
TI - Utilizing data systems to develop and monitor occupational health programs in a
large Canadian hospital.
AB - With rapid change in health care requiring greater emphasis on productivity and
quality management, occupational health hazards in hospitals have been receiving
increasing recognition, now not only focusing on controlling infection, but also
on chemical, physical, mechanical as well as psychosocial hazards. Reducing
costly time loss from musculoskeletal injuries is a particular imperative. The
Department of Occupational and Environmental Medicine at Winnipeg's Health
Sciences Centre, developed databases to help priorize, monitor and improve
occupational health programs for its 6,000 employees. Risk assessment/risk
management models were adopted to identify hazards, quantify risks and priorize
intervention. Using the databases permitted the targeting of groups requiring
immunization, resulting in increased coverage. New safety products were
introduced and found to be cost-beneficial. A return-to-work post-injury program
was particularly cost-beneficial. Over the five years following the
implementation of occupational health programs, workers' compensation assessment
reductions resulted in savings of more than half-a-million dollars annually. The
databases were invaluable in affecting these changes.
PMID- 9656651
TI - HRA model for hypercholesterolemia based on a longitudinal health database.
AB - To evaluate the risk factors for hypercholesterolemia, we examined 4,371 subjects
(3,207 males and 1,164 females) who received medical checkups more than twice at
an AMHTS in Tokyo during the period from 1976 through 1991; and whose serum total
cholesterol was under 250 mg/dl. The mean follow-up duration was 6.6 years. A
self-registering questionnaire was administered at the time of the health
checkup. The endpoint of this study was the onset of hypercholesterolemia when
the level of serum total cholesterol was 250 mg/dl and over. We compared two
prognosis groups (normal and hypercholesterol) in terms of age, examination
findings and lifestyle. After assessing each variable, we employed Cox's
proportional hazards model analysis to determine the factors related to the
occurrence of hypercholesterolemia. According to proportional hazards model
analysis, total cholesterol, triglyceride and smoking at the beginning, and
hypertension during the observation period were selected in males; and total
cholesterol at the beginning and age were selected in females to determine the
factors related to the occurrence of hypercholesterolemia.
PMID- 9656652
TI - A health condition survey of Japanese people in the prime of life, based on
national MHTS and human dry dock statistics.
AB - A health condition survey was made of Japanese persons in the prime of life
regarding six abnormalities (obesity, impaired glucose tolerance, hypertension,
hypercholesterolemia, hypertriglyceridemia, liver dysfunction) occurring with
high frequency. It was demonstrated that impaired liver function and elevation in
blood cholesterol are the main causes of health deterioration in persons in the
prime of life. The survey results suggest that the deterioration of their health
is associated with their lifestyle.
PMID- 9656653
TI - Elimination of inter-institutional discrepancies in health check-up results:
standardization of diagnostic decision level and uniformity of examination data.
AB - In Japan, more people are taking AMHTS and the number of medical institutions
where it is provided is also increasing. AMHTS is expected to continue to expand
in scope and importance from now on. People do not necessarily take AMHTS at the
same medical institutions year after year. For AMHTS to be truly useful from the
viewpoint of preventive medicine and be able to continue its development, it is
imperative that the level of diagnosis be standardized and the compatibility of
examination data be established among different institutions. The Japan Society
of MHTS is conducting pilot studies of reversed quality control (RQC) as part of
its activities with the aim of clearly understanding inter-institution gaps
regarding AMHTS and to establish uniformity in examination data.
PMID- 9656654
TI - Health risk appraisal in the UK--some preliminary results.
AB - Information about a subject's lifestyle, personal past history and family history
of disease is obtained from a 70-item questionnaire. This information is then
used to compute the subject's risk of dying from certain diseases, relative to
the average risk for a person of the same age and sex.
PMID- 9656655
TI - Dietary balance chart for an on-line computerized graphical support system in
MHTS.
AB - Dietary habits are believed to play an important role in the etiology of adult
disease. For this reason, it is necessary to include effective dietary guidance
in multiphasic health testing and services (MHTS) programmes for primary disease
prevention. We have developed such a programme of simple dietary advice, using a
computer system for the MHTS. Examinees' dietary habits are checked using optical
character record (OCR) questionnaire forms, and the results are displayed on the
screen of a colour display terminal. They are required to prepare a menu of their
usual daily dietary intake in terms of quantity and type of food. Thus the data
collected relate to the nutritional composition of the examinee's usual diet.
Nutritional requirements of the Japanese according to sex, height, and level of
physical activity, in accordance with criteria set by the Japanese Ministry of
Health and Welfare, are fed into the computer in advance. For each examinee,
these criteria and the results of the assessment of the diet are displayed
together on the screen in the form of colour graphs for comparison.
PMID- 9656656
TI - Prevalence and conditions of urinary incontinence among the elderly.
AB - In Japan, elderly disorders and diseases have markedly increased in recent years,
because of rapid aging and an increasing number of older persons. The situation
is creating serious social and community problems. These disorders, particularly
dysuria and urinary incontinence (UI), disturb the quality of life (QOL) in
latelife. Few reports on UI have been published, but precise investigation into
the community level remains to be made. Our presentation is the development,
implementation and evaluation of elderly UI in Kumamoto Prefecture. This study
includes 2,304 people (male: 856, female: 1,448), over 65 years of age, living in
two different communities; one is an urban (K) and the other is a typical rural
area (S). The rate of UI was in homebound elderly persons, male: 4.7%, female:
11.3%, and in nursing home residents, male: 16.2%, female: 23.2%. The condition
of UI was: almost Urinary Urgency in male (61.5%), and Stress Incontinence (such
as, caused by coughing, sneezing, and exercise) in female (46.3%). The influence
of UI on the activity of daily life was investigated. Most of the male cases were
giving concerns for family and community. In contrast, females hesitated to
participate in group excursions and outdoor exercise, and had a tendency to live
alone or indoors. However, most persons (81.5%) with UI did not visit a
physician. From this investigation, we conclude that a community health care
program and public support system are essential for proper understanding and
solution of the elderly UI problem.
PMID- 9656657
TI - Total quality in information systems management: issues for the health care
industry.
AB - Faced with rising costs, growing demand and declining funding, hospitals and
others must either cut services or improve the efficiency and effectiveness of
what they do. Neither solution can be implemented without adequate relevant
information. Without understanding which services are providing the most value to
its customers, sensible cutbacks will be difficult to make. Improving efficiency
requires a knowledge of where there are inefficiencies, and improving
effectiveness requires an understanding of what the outcomes of health care are.
The solution, as many have documented, is to create, as a first step, a database
containing detailed health care patient data. In this paper, we present
continuous improvement techniques as a requirement for the design and development
of this much needed database.
PMID- 9656658
TI - The SNOMED model: a knowledge source for the controlled terminology of the
computerized patient record.
AB - This article will present a description of the semi-implicit semantic properties
of the Systematized Nomenclature of Human and Veterinary Medicine, also called
SNOMED International. It will focus on the formalism of SNOMED and its
computational properties using the disease definition as an example. Additional
information will be provided in order to convert semi-implicit links found
between SNOMED concepts into explicit computational semantic links.
PMID- 9656659
TI - Informatics in the service of health, a look to the future.
AB - The paper attempts a balanced look at the directions of health informatics
required in the future. In a high level review of impediments to health and
health care a number of issues are identified that may be amenable to improvement
by contributions from health informatics. Attention is drawn to the improvement
of the collection and dissemination of knowledge in addition to the analysis of
morbid conditions as a focus for health informatics. On this basis a review of
the current state of health information systems is undertaken. The importance of
adaptable user interfaces for end users and systems personnel, privacy and
confidentiality protection, and linkage among clinical support systems and
knowledge repositories is stressed. These improvements hinge on advancements in
medical concept representation. Canadian contributions to these developments,
particularly the instigation of Evidence Based Medicine (EBM) are briefly
reviewed.
PMID- 9656660
TI - Tailoring communications for primary care settings.
AB - In more and more medical settings, physicians have less and less time to be
effective communicators. To be effective, they need accurate, current information
about their patients. Tailored health communications can facilitate positive
patient-provider communications and foster behavioral changes conducive to
health. Tailored communications (TCs) are produced for an individual based on
information about that person. The focus of this report is on tailored print
communications (TPCs). TPCs also enhance the process of evaluation, because they
require a database and the collection of patient-specific information. We present
a Tailoring Model for Primary Care that describes the steps involved in creating
TPCs. We also provide examples from three ongoing studies in which TPCs are being
used in order to illustrate the kinds of variables used for tailoring the
products that are developed and how evaluation is conducted. TPCs offer
opportunities to expand the reach of health professionals and to give
personalized, individualized massages in an era of shrinking professional contact
time.
PMID- 9656661
TI - Informatics methodologies for evaluation research in the practice setting.
AB - A continuing challenge in health informatics and health evaluation is to enable
access to the practice of health care so that the determinants of successful care
and good health outcomes can be measured, evaluated and analysed. Furthermore the
results of the analysis should be available to the health care practitioner or to
the patient as might be appropriate, so that he or she can use this information
for continual improvement of practice and optimisation of outcomes. In this paper
we review two experiences, one in primary care, the FAMUS project, and the other
in hospital care, the Autocontrol project. Each project demonstrates an
informatics approach for evaluation research in the clinical setting and
indicates ways in which useful information can be obtained which with appropriate
feed-back and education can be used towards the achievement of better health.
Emphasis is given to data collection methods compatible with practice and to high
quality information feedback, particularly in the team context, to enable the
formulation of strategies for practice improvement.
PMID- 9656662
TI - Periodical multiphasic screening and lung cancer prevention.
AB - The purpose of this work is to evaluate the utilization of information gathered
by multiphasic screening with respect to lung cancer detection and smoking
cessation techniques. A cohort (follow-up) study is reported in which cancer
incidence and factors affecting its occurrence are evaluated in a group of about
20,000 presumably healthy adults along a period of approximately 10 years
following comprehensive multiphasic health examinations. Lung cancer occurrence
is primarily related to smoking. The risk is higher in smokers and is dose
dependent; OR = 0.21, (CI = 0.08, .53) in never smokers, OR = 1.53 (CI = 0.8,
3.2) in past and current moderate smokers, OR = 4.92 (CI = 2.18, 11.11) in
current heavy smokers. Moreover, smokers with compromised pulmonary function
(FEVI/FVC < 75%) are at an even higher risk of developing lung cancer OR = 4.22
(CI = 2.2, 8.2) for past and current moderate smokers; and OR = 10.7 (CI-2.5,
38.6) in current heavy smokers. Information gathered in periodical multiphasic
health examinations could be utilized by health professionals to encourage
smoking cessation and smoking prevention in the appropriate screenees. Various
elements of the multiphasic test results could contribute to such prevention
efforts. While every smoker should receive appropriate evaluation and
consultation regarding nicotine dependence, smokers with reduced pulmonary
function represent an extra high risk group to which special attention should be
given.
PMID- 9656663
TI - Obstruction of valid race/ethnicity data acquisition by current data collection
instruments.
AB - Methods of collecting race/ethnicity data affect the validity of conclusions
based on them as do other factors such as lack of consensus and inadequate
definitions for terminology; and misclassification or miscounting of patients.
Current data collection instruments do not identify mixed heritage. We propose
improving data measurement and collection by including a quantified
multiracial/multiethnic heritage category for persons of mixed heritage; a don't
know category; and a refuse to reveal category. The resulting problems affect all
uses of racial and ethnic data, including health care provision, research, and
health planning. More precise race/ethnicity categories should be encouraged by
such means as a 16-category checklist (with instructions to check all which
apply) currently in development. The Methods section of all clinical,
epidemiologic, and pharmacologic reports should include descriptions of racial
measurement and reasons for including or excluding clearly defined populations.
PMID- 9656664
TI - Evaluation of complication rates after coronary artery bypass surgery using
administrative data.
AB - Our objectives were (1) to determine if studying hospital complication rates
after coronary artery bypass graft (CABG) surgery provides information not
available when only mortality is studied, and (2) to reexplore the utility of ICD
9-CM administrative data for CABG outcomes assessment. Using data from
Massachusetts, we identified CABG cohorts from 1990 and 1992 to respectively
develop and validate multivariate risk adjustment models predicting in-hospital
mortality and complications. The resulting models had good discrimination and
calibration. In 1992, adjusted hospital complication rates ranged widely from
13.0% to 57.6%, while mortality rates ranged from 1.4% to 6.1%. Hospitals with
high complication rates tended to have high mortality (r = 0.74, p = 0.006), but
2 of the 12 hospitals studied ranked quite differently when judged by
complications rather than mortality. We conclude that (1) complications after
CABG occur frequently and may provide information about hospital quality beyond
that obtained from hospital mortality rates, and that (2) administrative data
continue to be a promising resource for outcomes research.
PMID- 9656665
TI - Interactive video assists in clinical decision making.
AB - The Hawaii Quality and Cost Consortium began a project in 1993 to implement and
evaluate interactive videodisk programs to assist in clinical decision-making for
breast cancer. Communication problems between physicians and patients,
limitations of available outcomes data and varying preferences of individual
patients can result in treatment outcomes that are less than satisfactory. Shared
Decision-making Programs (SDPs) were developed by the Foundation for Informed
Medical Decision Making (FIMDM) in Hanover, New Hampshire, to assist in the
treatment decision-making process. Utilizing interactive videodisks, the programs
provide patients with clear, unbiased information about available treatment
options. With this information, patients can become more active participants in
making treatment decisions. The SDPs for breast cancer were implemented at two
sites in Hawaii. Evaluation data from 103 patients overwhelmingly indicate that
patients find the programs clear, balanced and very good or excellent in terms of
the amount of information presented and overall rating.
PMID- 9656666
TI - [Regulation and pathophysiology of airway secretion].
AB - Although excessive production of sputum is one of the characteristic features of
acute and chronic respiratory infections, bronchiectasis, diffuse
panbronchiolitis, chronic bronchitis and asthma, pathophysiological mechanisms
underlying airway hypersecretion remain uncertain. The increase in intraluminal
mucus may lead to impairment of airway mucociliary clearance and deterioration of
bronchial obstruction. Airway surface fluid is composed of mucus glycoprotein
released from submucosal glands and goblet cells and water from airway epithelial
cells, and the secretory function can be regulated by autonomic nervous system
and a variety of chemical mediators. It is thus important to select
mucoregulating drugs after understanding the mechanisms of hypersecretion and
impaired mucociliary transport under individual conditions.
PMID- 9656667
TI - [A guide for the timing of peripheral blood stem cell harvest in patients with
lung cancer].
AB - Harvest of peripheral blood stem cells (PBSC) was performed 57 times in 17 lung
cancer patients after standard-dose chemotherapy (cisplatin, etoposide)
supplemented with granulocyte-colony stimulating factor (G-CSF). In every case,
more than 1.5 x 10(6)/kg CD 34+ cells were collected by 2-5 apheresis.
Statistical significance was noted between peripheral leukocyte counts (WBC) and
collected CD 34+ cell counts (p = 0.0298), between peripheral platelet counts and
collected CD 34+ cell counts (p = 0.0009), and between the peripheral immature
granulocyte ratio and collected CD 34+ cell counts (p < 0.0001). Because of the
remarkable relationship between collected CD 34+ cell counts and peripheral WBC
counts, peripheral platelet counts and the peripheral immature granulocyte ratio,
these parameters were useful for determining the correct timing of PBSC harvest.
PMID- 9656669
TI - [Clinicopathological study of six cases of primary pulmonary lymphoma diagnosed
by gene rearrangement analysis].
AB - We report six cases of primary pulmonary lymphoma in which a gene-rearranged band
was shown by Southern blot analysis of transbronchial or surgical biopsy
specimens. The cases were 3 mens and 4 women with an average age of 59.6, who had
abnormal pulmonary shadows on chest X-ray. Two cases had Sjogren's syndrome and
one case had monoclonal gammopathy (IgM-lambda type). Histopathologic and
immunologic examination revealed diffuse infiltration of small lymphocytes (B
cell type) in all cases, and histological features of lymphoepithelial lesion or
lympho-cytic interstitial pneumonia (LIP) in three cases. CT revealed an ill
defined margin, air-space consolidation, and air-bronchogram in all cases. A CT
angiogram sign was apparent in 2 cases. In all cases, Southern blot analysis of
the tissue obtained from transbronchial or surgical biopsy revealed a gene re
arranged band, supporting the diagnosis of primary pulmonary lymphoma. We infer
that an ill-defined margin, air-bronchogram and air space consolidation on CT
were associated with the histopathological features of primary pulmonary
lymphoma.
PMID- 9656668
TI - [Effect of adenosine and its analogues on microvascular leakage in the rat
trachea].
AB - We examined the effects of adenosine and its analogues on vascular permeability
in rat trachea using Evans blue dye as a marker for plasma leakage. Inhalation of
N6-2-(4-aminophenyl) ethyladenosine (APNEA), a specific A 3 receptor agonist,
increased microvascular leakage in a dose-dependent manner, but adenosine, [R]-N6
(1-Methyl-2-phenylethyl) adenosine (R-PIA), aspecific A 1 receptor agonist, and
5'-(N-ethyl-carboxamide) adenosine (NECA), a specific A 2 receptor agonist, had
no effect. Inhalation of capsaicin increased vascular permeability in a dose
dependent manner. Pretreatment with NECA (10-1000 nmol/kg, i.v.) but not
adenosine (100 nmol/kg i.v.), R-PIA (100 nmol/kg, i.v.) or APNEA (100 nmol/kg,
i.v.) inhibited microvascular leakage produced by capsaicin aerosol (3 x 10(-5)
M) in a dose-dependent manner. However, NECA (10-100 nmol/kg, i.v.) failed to
inhibit substance P aerosol (10(-4) M)-induced extravasation of the dye. These
findings suggest that stimulation of adenosine A 3 receptors produces airway
vascular permeability, and that A 2 receptors inhibit neurogenic plasma
extravasation, presumably by inhibiting the release of tachykinins from sensory
nerves.
PMID- 9656670
TI - [Determinant factors of pulmonary function and respiratory muscle strength on
exertional dyspnea in patients with chronic obstructive pulmonary disease
(COPD)].
AB - The effects of pulmonary function and respiratory muscle strength on exertional
dyspnea in patients with chronic obstructive pulmonary disease (COPD) have not
been fully elucidated. We examined the relationships between pulmonary function,
static respiratory pressure, and dyspneic sensation during exercise in 48
patients with COPD. Dyspneic sensation during exercise was quantitated by a Borg
scale slope (BSS, BS/VO2) and the threshold load of dyspnea (TLD). BSS was
negatively correlated with VC, FEV1, V 25, RV/TLC (%). DLCO and PImax, whereas
TLD was positively correlated with VC, FEV1, V 25, FRC and RV/TLC. Linear
regression analysis revealed that FEV 1 and FRC were independent predictors for
TLD, and that RV/TLC (%) was an independent predictor for BSS. These results
suggest that an increase of air trapping as indicated by RV/TLC may be a major
factor contributing to both decreased TLD and increased BSS, resulting in an
increased sensation of dyspnea during exercise in patients with COPD.
PMID- 9656671
TI - [Metastasis of small cell lung cancer to the parotid gland as the initial
clinical manifestation, followed by metastases to the pituitary gland and lumber
spinal cord].
AB - The patient was a 48-year-old woman. In January 1995, she noted swelling in the
left parotid gland, and saw an otorhinolaryngologist. Needle biopsy showed small
cell carcinoma, and she was subsequently admitted to our hospital. Chest
radiography revealed a tumor shadow in the hilus of the right lung. Bronchial
biopsy revealed small cell carcinoma of the lung (T 4 N 3 M 1, stage IV).
Chemotherapy, with a CDDP-VP-16 regimen, achieved no response. She later
developed bitemporal hemianopsia and abducens nerve palsy. Brain MRI revealed
metastasis in the pituitary gland. Chemotherapy and radiotherapy were efficacious
for only a few months. She also developed pain and numbness in the left leg,
attributable to intramedullary metastasis (L 1/2, L 4/5) shown on MRI. It is
extremely rare for a metastasis to the parotid gland to be the initial clinical
manifestation of a small cell lung cancer which later develops widespread
metastases to the pituitary gland and lumbar spinal cord.
PMID- 9656672
TI - [Two cases of severe adult varicella pneumonia].
AB - Varicella pneumonia is the most common complication of adult varicella. Symptoms
may be severe and the mortality rate high in patients who are immunodeficient or
pregnant. Symptoms may be mild and progression more favorable in adults
previously in good health. We report two cases of varicella infection complicated
by severe pulmonary involvement in adult patients who were previously healthy.
Case 1 was a 36-year-old male who 6 days after developing varicella was
clinically observed to have dyspnea and hemopytsis. He died of acute respiratory
failure on the following day. Case 2 was a 28-year-old male whose respiratory
symptoms started the third day after developing varicella. These symptoms were
relieved by treatment with acyclovir and gammaglobulin. Careful observation is
and an early treatment of varicella should be undertaken not only for patients
with suppressed cellular immunity, but also for healthy adults, to prevent severe
complications.
PMID- 9656673
TI - [A case of Wegener's granulomatosis which showed early spontaneous remission].
AB - An 80-year-old woman presented at our hospital on October 1995 with fever,
hemoptysis and a cavitary shadow on chest X-ray. Blood examination revealed an
accelerated erythrocyte sedimentation ratio and elevated CRP. Pulmonary
cryptococcosis was suspected, but serological tests and bronchoscopic examination
for cryptococcus were both negative. There was also no evidence of the
tuberculosis or malignancy. She was treated with the antibiotic cefpirome sulfate
intravenously for thirteen days. Her chest X-ray and abnormal blood test findings
became almost completely normal following the i.v. antibiotic treatment. In
February 1996 (2 months after her first admission), she had severe right cheek
pain, and Coldwell Luc's operation was performed after right maxillary sinusitis
was diagnosed. A high fever (39 degrees C) continued after surgery, and multiple
cavitary shadows were seen on chest X-ray. Blood examination revealed an
accelerated ESR, elevated CRP and slightly elevated c-ANCA. She was treated with
i.v. infusion of antibiotics and antifungal drug's, but did not improve.
Wegener's granulomatosis was diagnosed after transcutaneous lung biopsy and
histopathological examination of the maxillary sinus. Dramatic improvement was
seen following treatment with oral cyclophosphamide and prednisolone. Whether her
first remission was due to antibiotic treatment or spontaneous is an interesting
question.
PMID- 9656675
TI - [Non-small cell lung cancer metastatic to the stomach and the jejunum causing
intussusception: a case report].
AB - We report a case of lung cancer metastatic to the stomach and the jejunum.
Adenocarcinoma of the lingula (T 4 N 2 M 0) was diagnosed in a 45-year-old man,
who then underwent chemoradiotherapy. Bowel obstruction later developed due to
jejunal metastasis. Another metastasis was detected in the stomach. Laparotomy
revealed jejuno-jejuno-jejunal intussusception caused by the two lesions. The
jejunal and gastric lesions were identified as metastatic large cell carcinoma
arising from the lung. One month postoperatively, the patient died due to
disease. The literature has demonstrated that large cell carcinoma of the lung
tends to metastasizes. However, the complex bowel invagination and gastric
metastasis seen in our case are rare.
PMID- 9656674
TI - [A case of pleuritis caused by strongyloides in a carrier of T-cell lymphoma
virus type I (HTLV-I)].
AB - A 73-year-old woman was admitted to our hospital complaining of dyspnea, fever
and general edema. Chest roentgenogram showed bilateral pleural effusion and
cardiomegaly. Cardiovascular examination demonstrated atrial tachycardia and left
ventricle dysfunction, suggesting congestive heart failure. She was sero-positive
for human T-cell lymphoma virus I (HTLV-I). The dyspnea and general edema
improved after therapy for heart failure. Because the pleural effusion persisted
after therapy, thoracentesis was performed. The pleural effusion was an exudate,
and Strongyloides sterocoralis was detected by microscopy. Two courses of
thiabendazole (1,500 mg/day, 3 days) were given orally. After this therapy, the
pleural effusion improved markedly. This case suggests that Strongyloides
stercoralis may be a causative agent of pleuritis in HTLV-I endemic areas.
PMID- 9656676
TI - [A case of idiopathic interstitial pneumonia with marked increase of CA19-9 in
serum and BALF].
AB - A 84-year-old man was admitted with dyspnea. Chest X-ray and CT showed
honeycombing in the dorso-basal segments of the lung bilaterally. Idiopathic
interstitial pneumonia (IIP: chronic, typical type) was diagnosed in accordance
with the clinical criteria proposed by the Japanese Ministry of Health and
Welfare. An extensive examination revealed no malignancy. However, the CA 19-9
level in bronchoalveolar lavage fluid (BALF) was very high (5,700 U/ml). An
immunohistochemical test of lung tissue obtained by transbronchial lung biopsy
was positive for CA 19-9 in bronchiolar epithelial and goblet cells. This case
suggests that CA 19-9 is occasionally produced on a large scale in the lung of
patients with IIP.
PMID- 9656677
TI - [Legionella pneumonia caused by aspiration of hot spring water after sarin
exposure].
AB - A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March
20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache
and weakness of the lower limbs and oropharyngeal muscles. Despite these
symptoms, he visited a hot spring on the same day with his family. On March 25
th, his muscle weakness progressed, and a low grade fever appeared. His muscle
weakness disappeared 8 days after exposure to sarin, but respiratory failure
rapidly developed, necessitating artificial ventilation within four day after
hospitalization on March 28th. Chemotherapy with erythromycin,
imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of
sputum collected by bronchofiberscopy were positive for Legionella pneumophila,
serogroup I. His respiratory state improved, but subsequent infection with
Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata
caused his death 71 days after admission. Oropharyngeal muscle weakness caused by
sarin-mediated cholinesterase inhibition was strongly suspected as the cause of
hot spring water aspiration. Transbronchial lung biopsy revealed organizing
pneumonia with fibrosis. Bronchoscopic findings included redness, edema and
fragility of all visible areas of the airway, which was thought to be due to
bronchitis caused by Legionellosis.
PMID- 9656678
TI - [Pulmonary emphysematous changes associated with Pneumocystis carinii pneumonia
in an AIDS patient].
AB - A 60-year-old man was admitted to our hospital complaining of non-productive
cough. He had worked in Africa and received a blood transfusion after a traffic
accident in 1985. On admission, the patient had remarkable hypoxemia and a
decreased CD4+ lymphocyte count. A serological test for human immuno-deficiency
virus (HIV)-1 was positive. His chest radiographs showed diffuse reticular and
linear opacities, and broncoalveolar lavage findings established a diagnosis of
Pneumocystis carinii pneumonia (PCP). A high-resolution CT of the chest revealed
peripheral infiltrates and low attenuation areas (LAA) consistent with severe
emphysematous alterations. We administered high-dose methylprednisolone and
trimethoprim-sulphamethoxazole (TMP-SMX). Because of marked eosinophilia, TMP-SMX
was discontinued, and the patient was given inhaled pentamidine isothiocyanate.
Although there was a striking clinical improvement, the emphysema-like lesion on
chest CT remained unaltered. LAA on CT had been modest in 1994, but had markedly
enlarged during the three years thereafter, leading us to speculate that most of
the LAA lesions recognized on admission might have developed in association with
PCP. Pulmonary function tests showed an obstructive ventilatory defect and
impaired diffusing capacity. Although PCP classically presents with diffuse
ground-glass or fine granular opacities, thin-walled cavities or other atypical
findings have recently been reported, especially in AIDS patients. There have
been several reports about emphysema-like lesions associated with PCP. It was
suggested that these lesions might be due to lung parenchyma destruction induced
by HIV itself or increased elastase release from HIV-infected macrophages. This
is the first report of PCP with pulmonary emphysematous lesions in Japan.
PMID- 9656679
TI - [Invasive thymoma successfully treated with high-dose chemotherapy followed by
peripheral blood stem cell transplantation(PBSCT)].
AB - A 42-year-old man was admitted with chest pain. A large mass in the anterior
mediastinum was seen on a chest X-ray film and confirmed by CT. Surgery was
performed, but the tumor was nonresectable because it had invaded the aorta and
pulmonary artery, and had disseminated to the pericardium. Invasive thymoma
(stage IVa) was diagnosed He initially received two courses of ADOC (50 mg/m2 of
cisplatin, 40 mg/m2 of doxorubicin, 0.6 mg/m2 of vincristine, and 700 mg/m2 of
cyclophosphamide) at 3-week intervals. Four weeks after the 2 causes of ADOC, he
was given 300 mg/m2 of etoposide for five days followed by G-CSF subcutaneously
for peripheral blood stem cell collection. After the two courses of ADOC, he
received high-dose ICE (1.5 g/m2 of ifosfamide for four days, 400 mg/m2 of
carboplatin for three days, and 200 mg/m2 of etoposide for five days) followed by
peripheral blood stem cell transplantation (PBSCT). He was given G-CSF after
PBSCT, with subsequent rapid neutrophil and platelet recovery. The tumor
diminished remarkably in size and complete remission was confirmed pathologically
at subsequent thoractomy. Postoperatively, 50 Gy of irradiation was given. These
observations suggest that high-dose ICE followed by PBSCT in combination with an
ADOC regimen, surgery, and radiotherapy is highly effective and well tolerated in
patients with advanced nonresectable thymoma.
PMID- 9656680
TI - [A case of secondary invasive pulmonary aspergillosis originating from an
aspergilloma, successfully treated with itraconazole].
AB - A 65-year-old man was admitted to our division with of productive cough and
hemosputum. Chest radiographs and chest CT on admission showed old inflammatory
shadows in both upper lung fields and a fungus ball in the left upper lung field.
Despite antibiotic treatment, the patient's sputum volume increased and
Aspergillus niger was repeatedly cultured from his sputum. Chest radiographs
showed deterioration around the intracavitary fungus ball and a test for serum
aspergillus antigen was positive. Secondary invasive pulmonary aspergillosis
originating from aspergilloma was diagnosed based on his clinical symptoms,
radiographic features and laboratory data. Administration of fluconazole failed
to improve his clinical course and amphotericin B was discontinued because of
hypokalemia. Oral administration of itraconazole was a successful treatment.
PMID- 9656681
TI - [Cytokines produced by cells in bronchoalveolar lavage fluid from a patient with
primary pulmonary cryptococcosis].
AB - Cytokines in the culture supernatant of concanavalin A-stimulated
macrophages/lymphocytes isolated from bronchoalveolar lavage (BAL) fluid in a 29
year-old patient with primary pulmonary cryptococcosis were evaluated to study
the immune reaction against Cryptococcus neoformans in the lung. Before
fungicidal therapy, levels of interferon-gamma and interleukin-10 were markedly
elevated, and declined after therapy. There were no changes in interleukin-2 or
interleukin-4 throughout the clinical course. This result suggests that IFN-gamma
and IL-10 may be involved in the immune reaction against pulmonary
cryptococcosis.
PMID- 9656682
TI - [A case of sea water and sand aspiration during near drowning].
AB - A 46-year-old man who had been pulled under water by a tidal wave when an
earthquake occurred on July 12, 1993 was carried to our hospital the next day. He
soon needed endotracheal intubation and mechanical ventilation because he
expectorated sputa with sand and because arterial bloodgas analysis revealed
severe hypoxemia. Chest X-ray on admission showed diffuse small nodules and areas
of consolidation. Chest CT obtained on July 16 showed centrilobular small nodules
bilaterally and alveolar opacities in the peribronchial region. After therapy
with antibiotics and frequent bronchial lavages, sputum with sand disappeared on
the 14 th hospital day and chest X-ray film and laboratory data showed marked
improvement. He was discharged on October 1. A chest CT scan obtained on February
17, 1994 showed improvement of the small nodules. The areas of consolidation had
also improved, but remained as linear and nodular opacities, which were
considered to be organized lesions. There are few reports concerning radiographic
findings particularly CT findings, after aspiration of sea water and sand during
near drowning.
PMID- 9656683
TI - [Nodular bronchioloalveolar carcinoma with multiple small air spaces caused by
bronchiolectasis].
AB - A 67-year-old man was admitted to our hospital with a faint abnormal shadow in
the right S2 on January 1995. Chest CT showed a faint abnormal shadow about 3 cm
in diameter with multiple small air spaces. He was admitted again 18 months later
for surgical treatment because the shadow on chest X-ray had grown. Right upper
lobectomy was performed in June 1996 and pathohistological examination revealed
bronchioloalveolar carcinoma. Tumor cells along the walls of the alveolus were
recognized only in the periphery of the lesion. The center of the lesion was
fibrotic and multiple small air spaces ranging from 0.5 mm to 10 mm in diameter
were present. One cause of these air spaces was considered to be the "check
valve" mechanism, but the majority of the air spaces were derived from ectatic
bronchioli. These results suggested that bronchiolectasis had developed with
central fibrosis only in the tumor. Central fibrosis in this case had played a
significant role in determining the radiographic appearance of the lesion.
PMID- 9656684
TI - [Thresholding algorithms in automated static perimeter].
PMID- 9656685
TI - [Evaluation of the Swedish Interactive Thresholding Algorithm, a new thresholding
algorithm, of the Humphrey field analyzer in normal subjects].
AB - The Swedish Interactive Thresholding Algorithm (SITA) is a new thresholding
algorithm that aims to obtain the same quality of visual fields in a shorter
examination time than with the conventional up-and-down method. We investigated
the correlation between thresholds measured with the SITA algorithm and those
with the conventional up-and-down method in 47 eyes of 47 normal subjects. In
each test point, thresholds with the SITA accurate and with the SITA fast showed
significant correlation with those of the conventional method (r = 0.693, p <
0.0001 and r = 0.689, p < 0.0001, respectively). The mean deviation (MD) in the
conventional method and the difference between MD values of the conventional
method and SITA accurate and SITA fast were significantly correlated (r = -0.442,
p < 0.006 and r = -0.509, p < 0.00092, respectively). The examination times of
the SITA accurate and SITA fast were 48% and 27% of the conventional method.
Although the new thresholding algorithm enables us to perform perimetric
examination with relatively high accuracy, further investigations should be
conducted before we apply it to glaucoma cases.
PMID- 9656686
TI - [Influences of trabeculectomy combined with the use of mitomycin C on corneal
endothelial cells].
AB - We used a specular microscope to evaluate the corneal endothelial cells in 119
eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The
endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/-
standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a
decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of
variation increased by 1.9, and the average cell area increased by 6.82%. There
were no statistical differences as a whole in these values. Decrease in
hexagonality was more frequent in eyes with prior intraocular or glaucoma
surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial
cell density, an increase in coefficient of variation and an increase in
hexagonality. Eyes with postoperative flat anterior chamber showed significant
changes in each parameter. The findings show that trabeculectomy with topical
mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3
weeks after surgery.
PMID- 9656687
TI - [Choroidal venous dilatation in serous retinal detachment].
AB - We studied the correlation between choroidal venous dilatation, intrachoroidal
leakage of dye, and subretinal leakage from the choroid in patients with serous
retinal detachment unaccompanied by choroidal neovascularization. We reviewed 13
eyes with anamnesis of serous retinal detachment, 23 eyes without anamnesis, and
one eye of unknown status of a total of 37 eyes. Regarding the relationship
between subretinal dye leakage from the choroid in fluorescein angiography (FAG)
and choroidal venous dilatation in indocyanine green angiography (ICG), the point
of subretinal leakage (31 points) was on and/or in the neighborhood of the site
of choroidal venous dilatation in 87.1% of the 27 eyes, except for eyes of
unknown site of leakage in FAG. The point of subretinal leakage was within and/or
in the neighborhood of the intrachoroidal leakage of dye in ICG in 92% of the
eyes. In serous retinal detachment without choroidal neovascular membranes,
serous retinal detachment may be caused by breakdown of the outer retinal barrier
due to choroidal venous congestion and intrachoroidal diffusion.
PMID- 9656688
TI - [Use of a scanning laser tomograph to evaluate the optic disc of the normal
eyes].
AB - We evaluated the optic disc in 77 eyes of 77 normal volunteers using a scanning
laser tomograph (Heidelberg Retina Tomograph: HRT, version 1.11). Particular
attention was paid to age, refractive error, and disc size. The topographic
parameters included: cup area, C/D area ratio, rim area, cup volume, rim volume,
mean cup depth, maximum cup depth, cup shape measure, height variation contour,
mean RNFL thickness, and RNFL cross section area. There was a significant decline
in mean RNFL thickness and RNFL cross section area with increase in age (p <
0.05). The mean and maximum cup depths were significantly deeper in myopic eyes
(p < 0.05). Large discs had large values of cup area, C/D area ratio, rim area,
cup volume, mean cup depth, cup shape measure (p < 0.01), and maximum cup depth
(p < 0.05). Large discs had small values of mean RNFL thickness and RNFL cross
section area. Rim volume was independent of age, refractive error, or disc area.
PMID- 9656689
TI - [Relationship between age and thickness of the retinal nerve fiber layer in
normal subjects].
AB - We measured the thickness of retinal never fiber layer (RNFLT) in the
peripapillary area in 120 eyes of 60 normal subjects. We used a scanning laser
polarimeter, or Never Fiver Analyzer (NFA) by Laser Diagnostic Technologies, USA.
Measurements were made along the peripapillary ring with the diameter of 1.75
disc diameter (DD) and another one 0.8 mm away from the disc margin. The RNFLT
was not significantly correlated with age along The two rings. The RNFLT ratio of
total/nasal area significantly decreased with increase in age. There was an
increase in the difference of RNFLT between both eyes with increase in age in
spite of considerable interindividual variations. The RNFLT values along both
rings thus showed age-related changes in normal subjects.
PMID- 9656690
TI - [Surgical indications and results of primary pars plana vitrectomy for
rhegmatogenous retinal detachments].
AB - To evaluate the efficasy of primary vitrectomy for uncomplicated rhegmatogenous
retinal detachment associated with posterior hyaloid separation, a series of 63
eyes were reviewed retrospectively. The criteria for vitrectomy included not only
eyes with posterior retinal breaks but also those with multiple peripheral
retinal breaks. The reattachment rate was 92.1% (58 eyes) after the initial
surgery, and finally this increased to 100%. Of the 46 eyes with macular
detachment, good visual rehabilitation, i.e., visual acuity improved by 5 or more
lines, was obtained in 71.8% (33 eyes) one month postoperatively. There was no
statistically significant difference in the reattachment rate whether an
encircling procedure was also done or not. In eyes with lens opacity, cataract
surgery was also done and intraocular lenses were implanted uneventfully in all
but one myopic case. No serious complications such as proliferative
vitreoretinopathy were found throughout the follow-up period except for the high
incidence (53.8%) of cataractous progression. The results indicate that
vitrectomy, removing the peripheral vitreo-retinal traction directly, is an
effective procedure for primary rhegmatogenous retinal detachment. Vitrectomy
combined with cataract surgery is also proposed as a valuable strategy in
selected cases to maintain visual rehabilitation.
PMID- 9656691
TI - [A case of corneal abscess with impetigo contagiosa].
AB - Impetigo contagiosa often occurs on the face of children. Although the eyelid and
conjunctiva are frequently affected, no corneal involvement has been reported in
Japan. We encountered a case of impetigo contagiosa with corneal abscess. The
patient, an 8-year-old boy, complained of pain and presented with corneal abscess
and iritis in the right eye as well as eruptions in the inferior eyelid and
around the anterior nostrils. He was diagnosed as having impetigo contagiosa with
corneal abscess. Because the corneal abscess and eruptions occurred at the same
time and coagulase-positive Staphylococcus with identical drug sensitivity was
isolated from both lesions, we considered the corneal lesion as a part of the
impetigo contagiosa. When impetigo contagiosa occurs around the eye, especially
on the eyelids, a careful examination of the anterior segment of the eye is
needed.
PMID- 9656692
TI - [Indocyanine green video angiographic findings of frosted branch angitis in a
child].
AB - A 10-year-old boy presented with typical fundus findings of frosted branch
angitis in both eyes. Fluorescein angiography showed late-phase hyperfluorescence
in some active areas of vascular lesions. Indo-cyanine green (ICG) angiography
showed similar but less extensive hyperfluorescence along the frosted vessels and
in the disc. ICG angiography also showed filling delay in the choriocapillaris.
These findings suggest that frosted branch angitis is a manifestation of
inflammation in the retina and the choroid. Laboratory studies showed increase in
the toxoplasma titer at 1:10,240 and in the serum levels of alpha 1 and alpha 2
globulin. Frosted branch angitis in this case seemed to be the consequence of
local allergic reaction, or immune complex deposition, presumably due to
toxoplasma infections.
PMID- 9656693
TI - [Medial collateral ligament of the knee and its surroundings: MRI findings of
normal and abnormal structures].
AB - Normal and abnormal structures of the medial corner of the knee were evaluated
with coronal and axial MR images. MRI revealed 35 medial collateral ligament
(MCL) tears and 61 medial meniscus (MM) tears in 200 consecutive examinations.
Just under the MCL, little or no fluid retention was identified between the
superficial and deep layers of the MCL or between the MM and MCL in normal knees
and in cases of MM tears. At the anterior aspect of the MCL, the deep layer
merges with the capsule of the suprapatellar bursa, potentially leaving space for
fluid retention. Fluid collection posterior to the MCL was demonstrated in a few
cases. Fluid retention with edematous swelling just under the MCL was noted in
the cases of MCL tears. MM-MCL distances in the cases of normal structure, MM
tears and MCL tears were 2.1 mm, 2.7 mm and 4.7 mm, respectively. The deep layer
of the MCL, which was enhanced by the presence of joint fluid, was identified in
71% of cases.
PMID- 9656694
TI - [Clinical study of transcatheter arterial embolization for pulmonary
arteriovenous fistula].
AB - PURPOSE: To evaluate the efficacy of transcatheter arterial embolization for
pulmonary arteriovenous fistula (PAVF). MATERIALS AND METHODS: Eight patients
with 14 PAVFs were treated by TAE for feeding arteries. In 5 of 8 cases,
detachable balloons were used, and, in 3 of 8 cases, metalic coils were used for
embolization of the feeding arterial branch. Detachable balloons or a series of
metalic coils were placed at the feeding artery proximal to the fistula. The
diameter of detachable balloons was twice the diameter of the feeding arterial
branch. The diameter of metalic coils was 1 mm larger than the diameter of the
feeding artery. RESULTS: No complications were apparent in our cases. All PAVFs
were completely occuluded by the embolization of a feeding branch. One month
after the procedures, the arterial oxygen pressure increased to normal values in
all cases and clinical symptoms disappeared. On postcontrast CT, the fistulas
treated by the embolization of a feeding arterial branch were not enhanced.
CONCLUSION: The embolization of a feeding branch provided a radical cure for
PAVFs.
PMID- 9656695
TI - [Endoscopic findings of esophagitis in concurrent chemo-radiotherapy for lung
cancer].
AB - We performed esophageal endoscopy with concurrent chemo-radiotherapy for lung
cancer in 19 patients. Endoscopical examination proved that seven patients
(36.8%) had esophageal erosion or coating (grade 2), four patients (21.1%) had
ulcer or bleeding (grade 3) confined to the radiation field, and only one patient
(5.3%) had severe symptoms (WHO grade 3). There was a discrepancy between
patients' symptoms and endoscopical findings. Endoscopically proven esophagitis,
that is, erosion or coating (grade 2), and ulcer or bleeding (grade 3), was more
frequent in the daily low-dose chemotherapy group (5/5) than in the full dose
chemotherapy group (5/14) (p < 0.05). One patient with grade 3 endoscopial damage
showed less recovery in spite of three months medication. In concurrent
radiochemotherapy in which the radiation field includes the esophagus, careful
attention should be given to radiation esophagitis, which may be underestimated
when assessed on the basis of subjective symptoms alone. Therefore, endoscopy is
recommended even if patients have few complaints, and once the esophageal ulcer
is proven (grade 3), it should be closely followed up using endoscopy.
PMID- 9656696
TI - [Evaluation of 99mTc-DTPA-HSA abdominal imaging of protein-losing
gastroenteropathy].
AB - Abdominal images were obtained after the intravenous injection of 99mTc-HSA-D in
8 patients with protein-losing gastroenteropathy (PLG). Six neck images and 7
abdominal images were obtained in 11 patients with ischemic heart disease as a
control study. We evaluated all the images with respect to visualization, initial
appearance time, and movement of abnormal radioactivity. In 7 of 8 patients with
PLG, abnormal radioactivity in the intestine appeared from 10 min to 4 hours
after injection, and moved 6 hours after injection. In 6 of 7 abdominal images of
control cases, slight activity was observed in the alimentary tract 6 hours or 24
hours after injection. The thyroid was not visualized in any of the 6 cases. In
conclusion, if radioactivity in the alimentary tract was first observed 6 hours
or later after injection, the diagnosis of PLG may be difficult by this method
alone. It still may be necessary to perform the alpha 1-antitrypsin test for the
correct diagnosis of PLG.
PMID- 9656697
TI - [Radiobiological considerations for stereotactic irradiation].
AB - Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a
single high dose) was initially developed by Leksell for non-malignant brain
lesions, but there has been increasing interest in using it to treat small
primary brain tumors or metastases. In more recent years, stereotactic
radiotherapy (SRT: fractionated STI) has been developed, but radiobiological
factors have not been sufficiently evaluated in relation to these techniques.
Larson classified potential STI targets into four categories according to whether
the target tissue is early- or late-responding and whether it is embedded within
or only surrounded by normal tissue. We have actually calculated biologically
effective doses for these categories to determine the indications for SRS and
SRT, and to be able to choose suitable SRT schedules. Based on our calculations,
theoretically SRS would be recommended for AVMs and benign tumors having distinct
margins separating them from surrounding normal tissue and SRT would be
recommended for low or high grade astrocytomas without clearly defined boundaries
and metastasis. Recommended SRT schedules would be 49 Gy/7 fractions, 52 Gy/8
fractions or 54.9 Gy/9 fractions completed within 2 weeks. However, clinically,
these indications and SRT schedules should be modified according to the many
other factors involved in individual cases, such as tumor size, presence of tumor
necrosis, the patient's general condition, prognosis, and so on.
PMID- 9656698
TI - [3D-CT cystography with perspective volume-rendering].
AB - We evaluated the clinical utility of 3D-CT cystography using the perspective
volume rendering technique in 5 patients with disorders of the urinary bladder
and prostate. Unlike the conventional orthostatic volume-rendering technique, the
capability of optional visual point settlement in the urinary bladder precluded
cutting a subset of acquired data for luminal inspection, and permitted
observation closer to lesions. Consequently, the technique enabled the evaluation
of the accurate size, shape, and relation to adjoining mucosa and the region
shaded by bulky tumor. 3D-CT cystography using the perspective volume-rendering
technique facilitated 3-D inspection of the bladder lumen.
PMID- 9656699
TI - [Clinical usefulness of ultrasound (US) database and reporting system].
AB - Our US database and reporting system is a relational database designed for US
image-management and navigation through volumes of US images, ACR code, text and
diagnostic reports. This program, running on a network of Unix servers and
Macintosh clients, supports jukebox 5 inch optical disks for data storage. With
simple keywords for ACR code, we can make a cross-reference and categorize US
images of teaching files.
PMID- 9656701
TI - [A trial to reduce cardiac motion artifact on HR-CT images of the lung with the
use of subsecond scan and special cine reconstruction algorithm].
AB - We describe our trial to reduce cardiac motion artifacts on HR-CT images caused
by cardiac pulsation by combining use of subsecond CT (scan time 0.8 s) and a
special cine reconstruction algorithm (cine reconstruction algorithm with 180
degree helical interpolation). Eleven to 51 HR-CT images were reconstructed with
the special cine reconstruction algorithm at the pitch of 0.1 (0.08 s) from the
data obtained by two to six contagious rotation scans at the same level. Images
with the fewest cardiac motion artifacts were selected for evaluation. These
images were compared with those reconstructed with a conventional cine
reconstruction algorithm and step-by-step scan. In spite of its increased
radiation exposure, technical complexity and slight degradation of spatial
resolution, our method was useful in reducing cardiac motion artifacts on HR-CT
images in regions adjacent to the heart.
PMID- 9656700
TI - [Normal sternal bone marrow MRI using STIR].
AB - The MR signal of sternal bone marrow was examined in 21 normal volunteers using a
sagittal STIR sequence. Craniocaudal phase-encoding with a hand-made positioning
device effectively eliminated artifacts due to cardiac pulsation. The sternal
bone marrow signal could be classified into three patterns based on the signal
distribution. The superior segment of the manubrium showed characteristic age
related changes. This method provided high spatial resolution and excellent bone
marrow imaging. Knowledge of a normal marrow signal pattern may be useful for the
evaluation of hematological disorders.
PMID- 9656702
TI - [Vascular endothelial cell injury in allergic vasculitis].
PMID- 9656703
TI - [Usefulness of magnetite as an MRI contrasting agent in an experimental cerebral
ischemic model. Evaluation of lesion detecting time].
AB - Gd-DTPA has a T1 shortening effect that enhances the contrast in MRI and is
widely used for the clinical evaluation of CNS diseases, though it is not
suitable for the detection of cerebral ischemic regions during the superacute
stage. Superparamagnetic iron oxide particles have a T2 shortening effect on
relaxation time, reducing signal intensity on T2-weighted MRI in normal cerebral
tissue. From this perspective we tested the feasibility of detecting ischemic
lesions during the superacute stage using superparamagnetic iron oxide particles
enhanced MRI. Male Sprague-Dawley rats were anesthetized using pentobarbital and
the left middle cerebral artery was permanently occluded (lt.-PMCAO) using a
modified version of the Koizumi method. After lt.-PMCAO, 100 mumoles Fe/kg, 1
ml/kg magnetite, superparamagnetic iron oxide particles, (magnetite-injected
group, n = 9) or physiological saline (vehicle-injected group, n = 9) was
injected into the femoral vein. T2-weighted MR images were performed at
designated time points immediately after injection of magnetite or vehicle on a
6.34 T MR unit. Additionally, in separate animals coronal sections of the brain
were stained with 4% 2, 3, 5 triphenyl-tetrazolium-chloride (TTC) to confirm the
infarct region. In the magnetite-injected group, a high signal area at the region
of lt.-MCA was visible within-20 to 30 min following lt.-PMCAO, whereas in the
vehicle-injected group no high signal ischemic area could be confirmed until 3 h
after lt.-PMCAO. Infarction was noticed in the TTC staining 3 h following lt.
PMCAO. In this study magnetite injection allowed the detection of ischemia in the
occluded MCA area on T2-weighted MRI during the superacute stage. These results
suggest that ischemia during the superacute stage can be evaluated using
magnetite enhanced MRI.
PMID- 9656704
TI - [Remote effect in patients with thalamic stroke. A study using positron emission
tomography].
AB - The purpose of this study was to investigate the functional relation between the
thalamus and other cortical regions in patients with thalamic stroke from the
view of cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen
(CMRO2) using positron emission tomography (PET). Twenty patients with thalamic
stroke (right lesion = 8, left lesion = 12) and 7 normal controls were studied.
Five patients were diagnosed as having thalamic infarction, and 15 (patients were
diagnosed) as having thalamic hemorrhage by X-CT and/or MRI scan. Regional
cerebral blood flow and cerebral metabolic rate of oxygen were measured by PET
using C15O2 and 15O2 steady state inhalation technique. In the left thalamic
stroke group, CMRO2 was significantly decreased in the left cingulate, superior
frontal, superior temporal, middle temporal, medial occipital, and thalamic
regions, compared with the normal control group. In the right thalamic stroke
group, CMRO2 was decreased in the left cingulate, medial occipital, right
hippocampal, thalamic, and the bilateral cerebellar regions, compared with the
normal control group. In the left thalamic stroke group. CBF was decreased
significantly in the left cingulate, middle temporal, hippocampal, thalamic, and
right cerebellar regions, compared with the normal control group. In the right
thalamic stroke group, CBF was significantly decreased in the right hippocampal,
thalamic and left cerebellar regions compared with the normal control group.
These results indicate that CBF and CMRO2 decrease in some distant regions from
thalamic lesions, perhaps due to a disconnection of neuronal fiber. Especially in
the left thalamic stroke group, CMRO2 was decreased in the ipsilateral temporal
regions. This result suggests that there are more intimate functional fiber
connections between the thalamus and temporal cortex in the left hemisphere than
in the right hemisphere.
PMID- 9656705
TI - [Assessment of regional cerebral blood flow in subcortical infarction with
aphasia].
AB - We assessed the regional cerebral blood flow (rCBF) in 8 patients with
subcortical aphasia and 8 patients with subcortical infarction without aphasia
using the N-isopropyl-P-[123I]-iodoamphetamine autoradiography (123I-IMP ARG)
method. In this study, we evaluated vermis to left cortex ratio of CBF. In cases
of Broca's aphasia (N = 2), CBF was lower in the posterior frontal regions
including Broca's area, and more hypoperfused in the posterior frontal and in the
posterior temporal regions, including Wernicke's area of total aphasia (N = 2).
But, it was not significantly hypoperfused in those regions in the cases of
Wernicke's (N = 2) and amnestic aphasia (N = 2). In the subcortical aphasia,
global CBF in the left cerebral cortex was lower than that in the right cerebral
cortex. However, in the subcortical infarction group without aphasia there was no
difference between CBF in the left cerebral cortex and the right cerebral cortex.
We conclude that hypoperfusion in the left cerebral cortex was greater than that
in the right cerebral cortex and it was probably due to dysfunction of the left
cerebral cortex when subcortical infarction occurred with aphasia. Though some
types of aphasia were not relative to the dysfunction of the left cerebral
cortex.
PMID- 9656706
TI - [A biomechanical study of anterior cruciate ligaments reconstructed with patella
tendons augmented by absorbable artificial materials. A biomechanical study in
rabbits].
AB - The purpose of this study was to investigate the biomechanical properties of
anterior cruciate ligament (ACL) reconstruction using an absorbable artificial
material in rabbits. Experimental studies were carried out on 58 New Zealand
white rabbits. After total resection of ACL, 22 knees were reconstructed with
patella tendons alone (non-augmented group) and 27 knees with patella tendons
augmented by polyglactin 910 mesh (augmented group). The animals were sacrificed
for biomechanical testing at 0, 2, 4, 6, 8, 12 and 24 weeks, respectively, after
the operation. The stiffness of reconstructed ACL in the augmented group showed a
mean of 26.58 +/- 5.78 N/mm at 8 weeks, and that of the non-augmented group 16.47
+/- 11.34 N/mm. There were significant differences between the augmented and non
augmented groups (p < 0.05). The ultimate load and energy of the reconstructed
ACL were also significantly higher in the augmented group than in the non
augmented group at 8 weeks. The mean elastic module was higher in the augmented
than in the non-augmented group, but the differences were not significant. The
mean tan delta of both groups was significantly higher than that of the normal
ACL at 24 weeks. These results suggests that polyglactin 910 mesh induces earlier
maturation of transplanted patella tendons biomechanically, and may be a useful
material for ACL reconstruction.
PMID- 9656707
TI - [A morphological study to elucidate the differences in visceral pleura in young
and old mice].
AB - The pleura is not only a mechanical envelope for the lung but also represents a
crossroad for the exchange of cells and fluids. We studied ultrastructural
differences in the visceral pleura of male mice in a young age group (aged 1 day,
1 week (wk), 2 wks) and an old age group (10 months (mos), 16 mos, 18 mos, 28
mos, and 30 mos), by both scanning and transmission electron microscopy. Surface
microvilli (SMV) of mesothelial cells appeared to be sparse at day 1, then
gradually increased in density and reached a plateau at approximately 10 mos. The
length of the SMV changed in parallel with density which was confirmed by a
morphometric study. After 28 mos, the SMV was partially loose, with an irregular
and thin appearance. The morphological properties of pleural connective tissues,
including collagen, elastin, and fibroblasts, changed in morphology with the
changes in mesothelial cells; the elastic layer beneath mesothelial cells formed
at 2wks and was maintained until 28 mos; collagen bundles increased in volume
density throughout life, whereas cellular components including mesothelial cells,
fibroblasts, and alveolar epithelial cells became atrophic with aging. From these
observations, we concluded that although SMV do not have any known functions in
the pleura, they change with age in a manner that likely corresponds to the
changes in pleural connective tissue as well as structural changes in lung
parenchyma.
PMID- 9656708
TI - [Hypoparathyroidism in maintenance dialysis patients (Pts)--a clinical study].
AB - With the recent development of measurement in intact PTH, increases of
hypoparathyroidism and adynamic bone disease have been reported in patients on
chronic maintenance dialysis. To clarify the frequency of hypoparathyroidism in
maintenance dialysis patients, the present study investigates the relationship
between the occurrence of hypoparathyroidism and clinical background, several
bone metabolic markers and the bone mineral density. We divided 298 maintenance
dialysis patients (HD 270, CAPD 28) without parathyroidectomy into 4 groups based
on intact PTH. Group A was absolutely hypo (intact PTH < 60 pg/ml), group B was
relatively hypo (60 < or = intact PTH < 160), group C was normal (160 < or =
intact PTH < 300), and group D was hyperparathyroidic (300 < or = intact PTH).
Groups A and B together accounted for 71.8% of the patients. The mean age in
groups A and B was higher than in group D (p < 0.05), and the dialysis duration
was shorter (p < 0.01). The concentration of 1, 25 (OH)2D was significantly
higher in groups A and B than in group D (p < 0.01), and remarkably higher in
group A than in group C. The level of Ca, i-P did not differ among the groups. In
our investigation of bone metabolic markers, group D was found to have
significantly higher Al-p, intact-BGP, and P 1 PC compared with the other 3
groups (p < 0.01), and the concentration of intact BGP was lower in group A than
in groups B and C (p < 0.01). The bone mineral density measured by DEXA did not
differ among the groups. The results suggest that, due to multiple factors, the
actual occurrence of hypoparathyroidism in maintenance dialysis patients is
higher than the predicted occurrence.
PMID- 9656709
TI - [An autopsy case of Hansen's disease (LLp) with numerous M. leprae].
PMID- 9656710
TI - [Diagnosis and treatment of joint injuries for athletes].
PMID- 9656711
TI - [Experience of intravascular malignant lymphomatosis with urinary incontinence
and gait disturbance].
PMID- 9656712
TI - On the role of G protein-coupled gating parameters in the human heart muscarinic
atrial potassium channel.
PMID- 9656713
TI - [A study of colonic mucins in two kinds of experimental colitis model in rat].
AB - We investigated the quantitative changes in colonic mucins of rats with colitis.
Male Wistar rats were treated with dextran sodium sulfate (DSS) or N
ethylmaleimide (NEM) to induce colitis. Both DSS and NEM caused depletion of
goblet cells, infiltration of inflammatory cells and erosion at the colonic
mucosa around the anus. Though the goblet cells decreased, colonic mucins
increased in the distal colon. These phenomena may explain the clinical features
of human ulcerative colitis, namely the goblet cell depletion and the mucous
stool. The increase of colonic mucins may be a compensatory function of the colon
tissue in response to the localized decrease of mucin production.
PMID- 9656714
TI - [Long-term clinical course and prognosis of patients with Crohn's disease].
AB - The aim of the present study is to clarify long-term clinical course, prognosis
and factors influencing prognosis of patients with Crohn's disease suffering for
more than 10 years. Sixty-eight patients (47 males, 21 females) with Crohn's
disease in whom the clinical course could observed well at our hospital for more
than 10 years were studied. We classified these patients into three groups (good,
fair, bad) according to their changes of IOIBD assessment score. And we compaired
some clinical factors in these groups to clarify factors influencing prognosis.
The results were as follows: 1) Twelve patients (18%) were in good prognosis
group, and 24 patients (35%) in fair one, and 32 patients (47%) in bad one. 2)
IOIBD assessment score at the time of diagnosis, site of leision, and
radiographic findings at the time of diagnosis showed significant difference
between bad prognosis group and the other two groups. Although there have been
many reports that Crohn's disease is generally progressive, our results indicated
that more than half of the patients showed favorable prognosis during the follow
up period for more than ten years.
PMID- 9656715
TI - [A case of cholerae O-139].
PMID- 9656717
TI - [A case of the primary abscess of the greater omentum].
PMID- 9656716
TI - [Five cases of colorectal cancer complicated with ulcerative colitis].
PMID- 9656718
TI - [A case of Cronkhite-Canada syndrome with multiple adenomas and a carcinoma of
rectum detected after improvement of polyposis due to steroid treatment--an
analysis of expression of p53 protein in polyps].
PMID- 9656719
TI - [A case of autoimmune hepatitis with anti-phospholipid syndrome].
PMID- 9656720
TI - [Heptocellular carcinoma (HCC) fed from cystic artery--report of a case and
review of the literature].
PMID- 9656721
TI - [Genetic hemochromatosis complicated with Schonlein-Henoch purpura showing
various gastro-intestinal disorders].
PMID- 9656722
TI - [A case of non-icteric middle-lower common bile duct cancer with intraductal
superficial spread to the gall bladder].
PMID- 9656723
TI - [An autopsy case of subcutaneous nodular fat necrosis associated with chronic
pancreatitis].
PMID- 9656724
TI - [A case of abdominal tuberculous lymphadenitis diagnosed by percutaneous US
guided needle biopsy].
PMID- 9656725
TI - Refusal to eat in the elderly.
AB - Refusal to eat by the elderly, and subsequent malnutrition, occurs in both
institutional and community settings. Causes include physiologic changes
associated with aging, mental disorders such as dementia and depression, and
medical, social, and environmental factors. Treatment approaches call for
management of these causes while considering the roles that medicine, ethics, and
culture play in the process.
PMID- 9656726
TI - Orexins: a newly discovered family of hypothalamic regulators of food intake.
AB - A family of neuropeptides from the hypothalamus, named orexins, was recently
discovered and characterized. Orexins stimulate appetite and food consumption.
Their genes are expressed bilaterally and symmetrically in the lateral
hypothalamus, which was earlier determined to be the "feeding center" of the
hypothalamus. In contrast, the so-called satiety center is expressed in the
ventromedial hypothalamus and is dominated by the leptin-regulated neuropeptide
network.
PMID- 9656727
TI - Interaction of chromium with insulin: a progress report.
PMID- 9656728
TI - Fish consumption and risk of sudden cardiac death.
AB - Studies show conflicting results regarding the protective effect of dietary fish
and fish oil on certain types of cardiovascular disease. A recent epidemiologic
study supports the hypothesis that moderate consumption (1-2 meals/week) of fish
lowers the risk of sudden cardiac death in humans.
PMID- 9656729
TI - Underreporting of energy intake, socioeconomic status, and expression of nutrient
intake.
AB - The relationship between socioeconomic status and nutrient intake was examined in
a recent study. The investigators used three different expressions of nutrient
intake in an attempt to overcome the confounding effect of underreporting on
interpretation of dietary intake data. Biologic validation attempts were
inconclusive as to which expression yielded the most accurate results.
PMID- 9656730
TI - High-fat meals and endothelial function.
AB - Two recent studies on the effects of single high-fat meals on endothelial
function have postulated an additional mechanism by which dietary lipids can
impact atherosclerosis. These studies found that dietary lipids decrease the
ability of blood vessels to dilate and that this modification of endothelial
function was protected by dietary antioxidants. Although this research presents
an interesting hypothesis, much more research is necessary to determine the
importance of dietary factors on vasoactivity.
PMID- 9656731
TI - Uncoupling proteins: beyond brown adipose tissue.
AB - Uncoupling protein, originally described in the inner mitochondrial membrane of
brown adipose tissue, permits the oxidation of fuels without the generation of
adenosine triphosphate (ATP). Closely related proteins have now been found in
many other tissues and shown to be regulated by thyroid hormones and dietary
factors. These uncoupling proteins may play a significant role in energy
expenditure, with implications for the development of human obesity.
PMID- 9656732
TI - "The German standpoint concerning science and education".
PMID- 9656733
TI - [Genesis and political background of "Sonderaktion Krakau" 6 XI 1939].
AB - The decision to imprison Cracow's University professors on November 6, 1939 was
made in connection with the establishment of the so-called General Government, as
a second stage of German security police action in nazi-occupied Poland to ensure
German rule also over Central and Southern Poland. By this way Sonderaktion
Krakau (Special Action Cracow)--as continuation of politische Flurbereinigung
(political cleaning up) started in German occupied Western Poland in September
1939--was a part of a second wave of persecution directed against the Polish
societies' social classes indicated by Nazi leaders and chiefs of German security
police as Poland's leadership, a wave of persecution now, since the end of
October 1939, enlarged on Central and Southern Poland. The imprisonment of the
Cracow Professors subsequently marked the perspective, that Poland's scientific
and academic institutions as a whole would be destroyed, so that in future no
Polish scientists, intellectuals and university people even would have the
possibility to do scientific work and to have subsistence from doing this kind of
work. As a consequence, Poland's intellectuals and university-trained people as a
social class in future would disappear indefinitely, and the people of Poland,
deprived of intellectual leadership, would be transformed into a mass of
dependend lower-class working people, so that the Nazi leaders mournfull future
scenario for their rule in German occupied Central and Eastern Europe would
become reality. By this way the imprisonment of the Cracow Professors on November
6, 1939 was the first step to realize Nazi future plans concerning Central and
Eastern Europe.
PMID- 9656734
TI - [The role of world opinion in rescuing Krakow scientists involved in the
"Sonderaktion Krakau"].
AB - The Author, participant and victim of the "Sonderaktion Krakau", remembers
circumstances of insidious imprisonment of Krakow professors performed on
November 6, 1939 by SS Operation Group under command of SS-Stumbannfuhrer Bruno
Muller. Based on archival research and relations of the participants of this
action, he reconstructs fate of the imprisoned scientists and he analyses
activities of political, governmental and diplomatic centers in Poland and
particularly abroad towards liberation of the prisoners. A significant role in
this international action was played by foreign scientific centers and
universities as well as world press agencies. Due to this multinational
solidarity, only 20 person out of 183 scientists imprisoned in the Sachsenhausen
and Dachau Nazi camps lost their lives. The article is supplemented by a list of
publications on the "Sonderaktion Krakau" written by ex-prisoners.
PMID- 9656735
TI - ["May we not waste their deaths..." Memories of a participant in the
"Sonderaktion Krakau"].
AB - The Author analyses the "Sonderaktion Krakau" from historical and cultural point
of view. Striking Polish science and national intellectual elite with an
insidious blow, the invader reached historical experiences. In the second part
the Author reconstructs fate of imprisoned professors and quotes many personal
observations from the period of his stay in the Sachsenhausen and Dachau Nazi
camps.
PMID- 9656736
TI - [Between hope and despair].
PMID- 9656737
TI - [Brain changes in dysraphic syndromes occurring in cases of meningomyelocele].
AB - Neural tube defects are the most common anomalies of the CNS in the group of
dysraphic syndromes. They occur on both encephalic and spinal levels. According
to the title of this article we discuss some characteristic examples of
intracranial, encephalic changes occurring in cases of meningomyeloceles. The
special position has to be attributed to Arnold-Chiari or Chiari malformation,
being currently under a nosological discussion. It is often restricted to its
most typical form-Chiari II syndrome. This is characterized by the neural tube
defect and the posterior fossa and brain-stem-cerebellum malformation with a
displacement into the foramen magnum. The compression of the fourth ventricle and
even secondary necrotic changes are also seen. Clinical symptoms depend on the
topography of pathological changes. Chiari II malformation coincides in the
majority of cases with meningomyeloceles and sometime with other spinal cord
malformations. Meningomyeloceles coincide often with anomalies within cerebral
hemispheres. Among them hydrocephalus deserves particular attention, occurring in
the majority of Chiari II cases and not being rare in cases of myeloceles. The
anomalies and/or secondary lesions of encephalic structures, particularly of the
cortical mantle are observed, depending upon the severity of hydrocephalus and
the onset of its development. Meningomyeloceles can also be accompanied by
cerebral hemispheres anomalies arising in the other pathomechanism and
developmental period than dysraphic syndromes. The midline malformations and
anomalies of commissural system are not rare among them. In conclusion we
emphasize that each case of CNS malformations is unique. The observed anomalies
have to be assessed whether they form a part of a leading syndrome or occur
together with dysraphic changes.
PMID- 9656738
TI - [Congenital defects of the spinal part of the neural tube].
AB - The abnormal closure of the neural tube results in defects of the nervous system
development, which are referred to as dysraphism. Considering successive steps of
the development of the human foetus, it can be estimated that spinal cord
malformations arise from pathologies of early foetal development between 17th and
28th day gestational age. This time period comprises a development of the neural
plate and subsequently neural tube. The development is completed with a closure
of a posterior aperture of the neural tube (caudal neuropore). Congenital
malformations are often caused by defective closure of the caudal neuropore. The
neural plate develops about 17th day gestational age, the cerebral vesicle
appears about 21st day and the neural tube forms between 17th and 20th day. The
rostral neuropore closes on the day 25th as does the caudal neuropore on the day
28th. The embryo is 2.5 mm long at the time. Noxious factors acting during that
period can affect normal closure of the caudal neuropore and distort the process
of spinal cord canalization. The resultant defect is called spina bifida. This is
the most severe form of dysraphism-rachischisis. Meninges are also affected in
this defect. They cannot cover the neural canal and on the margins of the lesion
are replaced by epithelium. In milder types of the defect lack of a complete bony
framework is concealed by soft tissues, forming a sac of variable size over the
lesion. Spina bifida can be subdivided according to the sac structure:
meningocoele, meningocysticoele, meningomyelocoele, meningomyelocystocoele.
Central canal pathologies constitute another form of spinal cord malformations
presenting as hydromyelia. Abnormal closure of the neural tube may affect
development of the vertebral column and spinal cord along their entire length or
only at a certain portion. Malformations are seen most frequently in the lumbo
sacral and then cervical regions.
PMID- 9656739
TI - [Open neural tube defects in prenatal diagnosis].
AB - The problem of open neural tube defects (ontd) is discussed in the light of
results of prenatal tests performed in the district of Warsaw. These results seem
to bear some epidemiological significance allowing estimation of approximate
frequency of ontd as well as recurrence risk for the purpose of genetic
counselling. Prenatal diagnosis of ontd is very important for individual families
-particularly those with increased risk. However, in view of very small number of
prenatal tests and the fact that maternal serum screening and ultrasonografic
screening are practically not available the demographic impact of prenatal
diagnosis in Poland on the frequency of ontd (and other genetic diseases) in
Poland must be negligible.
PMID- 9656740
TI - [Neural tube defects (NTD)--assessment from the perspective of 25 years of
studies].
AB - The present paper illustrates the authors 25-year experience in step by step
approach to the definition of environmental and genetic background of neural tube
defects. Based on the birth defects registry, a complete ascertainment of all
deliveries was performed in Southern Poland during two period: 1970-1972, and
1979-1981. The birth prevalence of neural tube defects (NTD), as well as other
CNS malformations was determined. The empiric recurrence risk was calculated as
3.2% +/- 1.6. Based on this figure, the relative risk (RR = 37.6 p < 0.001) and
heritability (h2 = 74.7 +/- 6.7) were estimated. Our own modification of Morton's
complex segregation analysis was applied. Three Mendelian (dominant, additive and
recessive) and one multifactorial model were tested. The results did not provide
a clear cut discrimination between different models; however the lowest 2 value
was obtained for additive inheritance with 61% of penetrance and the frequency of
sporadic cases equaled 55%. A search for genetic markers did not support the
hypothesis that HLA-A,B,C loci are equivalents of T/t like locus in mice. The
results of the study on transcobalamine levels in amniotic fluid may suggests
that different transcobalamine metabolism reflects phenotypic expression of
genetic susceptibility to NTD development. Current research and future
perspectives on genetic and environmental background of NTD are also presented.
PMID- 9656741
TI - [Congenital defects of the spinal cord and canal in neuroimaging].
AB - Authors present the clinical classification of spinal dysraphisms and discuss all
imaging modalities useful in the diagnosis: conventional X-rays, myelography,
computed tomography, myelo-CT and magnetic resonance imaging. They precise the
place of ultrasound in the prenatal and postnatal imaging of spinal dysraphisms.
PMID- 9656742
TI - [Prevention of neural tube defects. An important health and social problem].
AB - Central neural system congenital malformations in the form of neural tube defects
(ntd) belong to the most common diseases leading to very serious childrens'
disability and mortality. As it has been calculated, the number of children
affected with ntd, delivered in Poland every year is in the range of 800-1150.
Children with encephalocele participate in this number in app. 50%. As it has
been found, morbidity and mortality caused by the ntd remain high and stable in
Poland for the last 20 years. In the view of very limited possibilities of the
treatment offered by health services, prophylactic measures remain the best
methods for limitation of the problem. The primary prevention of ntd was
discovered in late seventies. It has been found that folic acid added to the diet
of women in the reproductive age reduced number of children born with ntd by 70%.
Authors present the Programme of Primary Prevention of ntd in Poland. This
Programme has been incorporated in the National Programme of Health for the
Nation 1996-2005.
PMID- 9656743
TI - [Psychologic and neuropsychologic evaluation of psychomotor development in
children with neurological diseases].
AB - Psychological and neuropsychological assessment of children is focused on
behavioral disorders of various dimensions (e.g., abilities and limits of
perceptual, expressive, cognitive and emotional functions). Additionally
neuropsychological diagnosis attempts to explain relationship between behavioral
and brain states. The purpose of diagnosis formulated in this way requires
careful selection of test procedures and overall integration of different kinds
of data. Especially, severally handicapped cases need this kind of diagnostical
approach. Limits of valid diagnostic conclusions are determined by many factors
that affect coherent interpretation of the test scores (e.g. the lack of a
consistently employed neurologic model of brain development to relate to
behavioral functions, significant impairment with coexisting sensory and motor
deficits, the different effects of brain lesion depending on age of onset, the
interference of maturational and experimental variables with manifestation of
brain damage).
PMID- 9656744
TI - [Liquidation of barriers: realization issues and legislative aspects].
AB - Designing for the handicapped persons, aiming at the liquidation of the barriers
is actually an essential part of the architects activity. It results from the
fact that the handicapped persons issue became the interdisciplinary one. The
architect, being responsible for the living space and environment creation, is to
design the friendly environment for the handicapped persons. The space favourable
for the handicapped is favourable for all. There are many aspects of the
designing for the handicapped; legislative or execution issues are the examples.
The legislative aspect is presented in this paper on the base of the contemporary
legal rules of the Polish Republic, whereas the execution aspect is introduced
and discussed on the basis of the two projects designed by the Design Bureau in
Cracow and being currently in realization. These are: housing & service unit
(Boruty-Spiechowicza Str., Cracow) and the Faculty of Philosophy complex at the
Jesuits College (Kopernika Str., Cracow).
PMID- 9656745
TI - [Directions and complex rehabilitation in children with neural tube defects].
AB - A child with spina bifida is born with a potential disability. These children
demand a long treatment and constant care of a specialist team which consists of:
a pediatrician, pediatric surgeon, neurologist, nephrologist, specialist in
rehabilitation and psychologist. In the treatment of the children with spina
bifida, rehabilitating treatment is the basic and main one, which is started in
the first days of life. The most difficult and trouble-some problem in the
treatment of the children with spina bifida is the dysfunction of urinary bladder
and anus sphincters which causes urine and fecal incontinence. These impairments
often cause infections of the urinary tract, nephrolithiasis and in the later
period, renal failure. The most vital factor influencing the effect of
rehabilitation in children with spina bifida, the one which causes a real
handicap, is the dysfunction of urinary bladder and anus sphincters, and not
paresis or paralysis of the extremities.
PMID- 9656746
TI - [Lower extremity deformities as an obstacle in rehabilitation of meningomyelocele
patients--pathogenesis and principles of treatment].
AB - The fate of 89 patients with meningomyelocele operated at the Institute of
Orthopedics and Rehabilitation in Poznan between 1970 and 1989 due to paretic
deformities of lower extremities has been traced by the authors. Deformities
prevented nursing, standing or ambulating; their type and results of treatment
have been related to the level of neurosegmental lesion. Modified Sharrard's
classification served to group the patients. The level of lesion established
during lower extremities muscles testing has been verified after neurological
examination supplemented with electrophysiological tests: sensory response within
L3-S2 dermatomes, afferent conduction velocity of the peroneal nerve and selected
muscles of lower extremity electromyogram. Deformities due to inadequate nursing
(hip and knee contractures and equinus foot) were the main obstacle in the
rehabilitation in patients with spinal Th12-L2 lesion. In patients with L3-L5
lesion hip contractures were accompanied by dislocation or subluxation of the hip
due to muscular imbalance. Knee contracture was less frequent in this group and
foot deformities were diverse. Surgical correction of paretic deformity of the
hip was the last stage of management designed to promote rehabilitation,
following previous foot and knee surgery. In patients with Th12-L2 lesion
recurrence of contractures made standing and walking impossible. In patients with
L3-L5 neurosegmental lesion surgery for paretic dislocation or subluxation of the
hip inclusive of open reduction, varus-derotation osteotomy of the proximal
femur, transiliac osteotomy and iliopsoas transfer to the greater trochanter
according to Mustard resulted in stable hip. Seventy percent of patients with L3
L4 lesion and all patients with L5 lesion profited from hip surgery with reduced
orthotic use and effective gait.
PMID- 9656747
TI - [Psychological consequences of neurologic motor impairment from a developmental
perspective].
AB - Human development is a process that continues throughout an individuals life. Any
change of structure of function, not only of a progressive type, is a
developmental change. Developmental defects of the neural tube, such an various
form of myelomeningocele, which manifest themselves during the early stages of
the intrauterine life, have an impact on the individuals further development. Its
intensity depends on the extend of the defect itself, the feasibility of its
correction (usually by surgical means) and a number of external, environmental
factors which have an indirect influence on a child's development. The
psychological consequences of such defects take the form of various disturbances
in the development of cognitive processes: mainly the perception of the outside
world and the formation of the cognitive structures involved in self-image
formation. At every stage of his and her development, an individual of with a
neural-tube defects is subject to many forms of social influence. These may
either stimulate or hamper development. It is possible that mental development
deficiencies observed in some individuals at a later stage result not so much
from the defect itself as from the lack of appropriate social stimuli. The
specific problems of children and adolescents (aged 13 to 17) with sacro-lumbar
myelomeningocele have been discussed on the basic of a pilot study conducted at
the hospital in Radziszow in the years 1996-1998.
PMID- 9656749
TI - [Neurosurgical treatment of spinal dysraphism in children].
AB - A tethered cord syndrome includes in its meaning all types of dysraphism in
children. The syndrome is described in regard to its etiology, pathophysiology
and clinical outcome. Next, the most prevalent types of dysraphism in children
are presented. A surgical approach in myelocele--the most frequent defect--is
discussed in detail. Reasons for taking a difficult decision not to operate are
considered. The most important operative problems are also reviewed. It is
reminded that myelocele often coexists with Arnold-Chiari malformation type II
and hydrocephalus. Problems in selecting an appropriate surgical approach in this
syndrome are shortly discussed. A rare syndrome of sacral agenesis, poorly
amenable to surgical intervention, is presented. There are also some less
frequent syndromes described, including:-sinus dermalis, potentially life
threatening in the case of recurrent meningitis;-lipomyelocele, needing early
identification and prophylactic surgical treatment;-diastematomyelia, in half of
the cases requiring surgery due to a bony spur;-retethered cord syndrome, an
iatrogenic complication of neurosurgical interventions done on the spinal cord.
PMID- 9656748
TI - [Therapy through architecture].
AB - The paper contains in its introductory part a short analysis of the problem of
disability giving the proposal of the strategy for solving the problem of opening
the built environment to the disabled people in Poland in the light of
experiences of the countries with accessibility legislation. Promoting the idea
that all people have only one thing in common--that they are different. To the
present time, in the world and in Poland, the amenities provided to disabled
persons could be regarded as being minimal in nature, satisfying basic needs. The
necessity of disabled persons on the dependence on others, and the lack of
independence has created a problem, whereby the disabled persons is unable to
fully participate in social and public life, as well as partake of cultural
amenities. Universal design is the architectural design philosophy in which the
needs of all environment users irrespective of their physical abilities, are
recognized in the natural way. At the end of this paper some interesting examples
of the German designs for disabled people are presented. The main focus of the E.
Feddersen & W. Herder Office is on the social aspect of architecture, especially
on the designing of tenements, schools, kindergartens, hospitals and homes for
the disabled, retarded and elderly people.
PMID- 9656750
TI - [Urologic aspects of myelodysplasias in children].
AB - At least 25% of the clinical problems seen in pediatric urology are the result of
neurologic lesions that affect lower urinary tract function. The advent of clean
intermittent catheterization and refinements in techniques of urodynamic studies
in children dramatically changed the way this pediatric population was
traditionally managed. Along with this change came a greater understanding of the
pathophysiology of the many diseases that primarily affect children. The
applicability of urodynamic testing has expanded to the point where most
pediatric urologic centers now believe that functional assessment of the lower
urinary tract is an essential element in the evaluation process and is as
important as x-ray visualization in characterising and managing these abnormal
conditions. The natural outcome of early functional investigation has been the
advocacy of proactive or early aggressive management of children who are now
considered at risk of urinary tract deterioration based on specific hostile
urodynamic parameters. This paper first defines the testing process as it applies
to children and second, conservative and surgery methods to prevent upper urinary
tract deterioration and to correct continence.
PMID- 9656752
TI - Early results of laparoscopic resection of colorectal cancer.
AB - OBJECTIVE: To study the immediate and early postoperative results obtained in
patients subjected to laparoscopic resection of colorectal cancer. PATIENTS AND
METHOD: A prospective, observational cohort study was initiated in January 1993,
involving 50 patients subjected to laparoscopic resection for colorectal
adenocarcinoma (rectal amputation in 10 cases, lower rectal resection in 13,
recto-sigmoidectomy in 18, and miscellaneous colectomies in 9 cases). Seventy
percent of the tumors were in IUCC stages II and III. Mean follow-up was 21
months. RESULTS: Conversion to open surgery was required in 18 cases (36%).
Intraoperative problems were limited to a single urethral lesion, while
postoperative complications were recorded in 11 patients (22%), and were managed
conservatively: a urinary fistula secondary to the aforementioned urethral
lesion; subclinical dehiscence of the anastomosis (2 cases); phlebitis (1 case);
infection of the surgical wound (4 cases), and urinary and pulmonary infection (1
case each). There were no differences between converted surgery (i.e.,
conventional laparotomy) and those operations completed endoscopically (with a
final assisted or combined minilaparotomy) in terms of the length of the surgical
resection piece, the length of the distal margin of the specimen or the number of
lymph nodes. Global hospital stay ranged from 9-12 days, versus 5-7 in the group
without complications. Global survival is 78% at 42 months, with a disease-free
interval of 53% at this time. CONCLUSIONS: Laparoscopic colorectal resection
presents an incidence of intra- and postoperative complications characteristic of
major surgery, with no differences in surgical specimen size with respect to
those operations converted to laparotomy. Global survival is similar to that
reported in the literature for open surgery.
PMID- 9656751
TI - [Possibilities of ambulation in children with myelodysplasia].
AB - The authors discuss the possibility of ambulation of children with
myelodysplasia, employing different types of orthopedic devices. According to the
personal experience of 23 myelodysplastic patients, the indications and results
of using reciprocal gait orthoses have been described. The paper emphasizes the
significance of interdisciplinary team in the treatment of this disease.
PMID- 9656754
TI - Histomorphometric changes after small bowel transplantation.
AB - AIM: Rejection results in destruction of the intestinal mucosa. This is the major
cause of morbidity and morbility in human allografts. The aim of this study was
to investigate histomorphometric changes in both the graft and recipient
intestinal mucosa after experimental orthotopic small bowel transplantation.
EXPERIMENTAL DESIGN: Using the pig model, 21 large-white pigs underwent:
laparotomy (n = 7) (control group); orthotopic small bowel transplantation
without immunosuppression (n = 7); and orthotopic small bowel transplantation
with cyclosporine A (n = 7). RESULTS: 1) Significant reduction of total mucosal
thickness (villi plus crypt) (p < 0.05) in both the graft and recipient mucosa;
2) Attenuation of this effect by administration of cyclosporine A, which reduced
the loss of mucosal thickness mainly at the expense of crypt hipertrophy.
CONCLUSIONS: These findings suggest that villi and crypt length measurements may
be a reliable method for monitoring rejection after small bowel transplantation.
PMID- 9656753
TI - Stromal tumors of the digestive tract. Prognostic value of mitotic index.
AB - OBJECTIVE: We analyzed the prognostic factors and evaluated the usefulness of
mitotic index to predict the behavior of gastrointestinal stromal tumors (GIST).
PATIENTS AND METHODS: Fifty three patients operated on for stromal tumors of the
digestive tract were studied retrospectively. Mean follow-up was 6 years. The
number of mitosis/10 high power fields was the definitive criterion for
classification, regardless of their inmunohistologic differentiation. Twelve
tumors had 0 mitoses, 34 from 1 to 9 mitoses, and 7 had > or = 10 mitoses. The
survival rate was analyzed and the morphological characteristics and evolution
were correlated according to mitotic index. RESULTS: The incidence of advanced
illness was related to the number of mitoses: 29% in the group with 1 to 9
mitoses, and 86% when there were > or = 10 mitoses. The recurrence intervals were
44 and 8 months respectively. No tumor with 0 mitoses evolved aggressively. The
survival rate was significantly related (p < 0.001), to the mitotic index. The
group with 0 mitoses had a survival rate of 100% after 10 years, those with 1 to
9 mitoses 69% and those with > or = 10 mitoses 14%. The other factors which
influenced the prognosis (location, size, local invasion and resection) depended,
as well, on the mitotic index. CONCLUSION: The classification of digestive tract
stromal tumors by mitotic index is an efficient method because it distinguishes 3
entities with different biological behavior in the long term.
PMID- 9656755
TI - Growth hormone reduces bacterial translocation in radiation enteritis in the rat.
AB - BACKGROUND: Radiotherapy may be considered as one of the most effective
treatments for digestive tumours. This procedure has major side effects,
especially in fast growing tissues like intestinal mucosa. The administration of
drugs that reduce or avoid radiation injury of the intestinal mucosa may be
clinically advantageous. Growth hormone is a peptide suitable for this purpose by
modifying cell proliferation within the intestinal crypt. MATERIAL AND METHOD:
Adult male Wistar rats were used in a model of abdominal irradiation. Each
irradiated animal received 1200 cGy under anaesthesia and was sacrificed four and
seven days later. The animals were treated with either saline or growth hormone
(1 mg/kg/day) beginning immediately after the irradiation treatment. On the day
of sacrifice, intestinal samples were taken for morphometric measurements and
mesenteric lymph nodes for bacterial translocation. RESULTS: Mortality was of 50%
approximately and was not affected by growth hormone treatment in irradiated
animals. Bacterial translocation increased (p < 0.05) in irradiated animals
whereas no significant increase was observed in rats treated with growth hormone.
Growth hormone promotes an earlier growth of intestinal villi in irradiated
animals (p < 0.05). CONCLUSIONS: Growth hormone promotes the morphologic
adaptation of intestinal mucosa after abdominal irradiation, reducing bacterial
translocation in rat.
PMID- 9656756
TI - [Therapeutic use of albumin: a discussion on its efficacy].
AB - The aim of our study is to discuss the current recommendations for the use of
intravenous albumin in hypoalbuminemic patients obtained from a literature
review. Some data available lead us to the belief that its use does not influence
the clinical outcome of the patients, in most of the cases in which it is
employed. Therefore its use should be limited to a certain number of clinical
situations, in which its efficiency has been clearly shown, as in new-born in
whom plasma expansion with small volume is necessary, in cases in which synthetic
colloids cannot be employed, in massive paracentesis in cirrhotic patients, in
selected cases of edema unresponsive to diuretics or other colloids in
plasmapheresis, in kidney and liver transplant surgery.
PMID- 9656757
TI - [Helicobacter pylori and gastric lymphoma].
PMID- 9656758
TI - [Perforated jejunal tuberculosis in a patient with HIV-infection].
AB - Patients with AIDS are particularly susceptible to tuberculosis infection with a
high incidence of extrapulmonary disease and surgical complications. Authors
describe a 38-year-old male infected with the human immunodeficiency virus who
presented intestinal perforation due to mycobacterium tuberculosis. A resection
of jejunum was performed with primary anastomosis. The postoperative course was
further compromised by hepatic failure and the patient died 16 days after the
initial surgery.
PMID- 9656759
TI - [Primary torsion of the omentum: preoperative diagnosis with abdominal
ultrasonography].
PMID- 9656760
TI - [Complications in biliary surgery with laparoscopy: lithiasis of the residual
cystic stump].
PMID- 9656761
TI - [Acute cholestatic hepatitis secondary to flutamide].
PMID- 9656762
TI - [Diagnosis of the supraelevator abscess].
PMID- 9656763
TI - [Cholestatic hepatitis caused by captopril].
PMID- 9656764
TI - Automatic classifiers for the interpretation of electrocardiograms.
AB - The morphological diagnosis of ECGs is a pattern recognition procedure. The way
the clinician does this is not clearly elucidated. Nevertheless, several models
aimed at achieving identical results by automatic means are empleyed. While in
the doctor's case this is not exactly so, the computer task for ECG
interpretation comprises two distinct and sequential phases: feature extraction
and classification. A set of signal measurements containing information for the
characterization of the waveform is first obtained. These waveform descriptors
are then used to allocate the ECG to one or more diagnostic classes in the
classification phase. The classifier can embody rules-of-thumb used by the
clinician to decide between conflicting ECG diagnosis and formal or fuzzy logic
as a reasoning tool (heuristic classifiers). On the other hand, it can use
complex and even abstract signal features as waveform descriptors and different
discriminant function models for class allocation (statistical classifiers). More
recently, artificial neural network techniques have also been used for signal
classification. The authors review feature selection techniques and
classification strategies, problems and methods of performance evaluation and
results obtained by different classification approaches. A brief discussion of
the relative merits of the two main types of ECG classifiers, logical and
statistical, is included.
PMID- 9656765
TI - [Thrombolysis in Portugal. Influencing the national reality].
PMID- 9656766
TI - [Clinical manifestations and therapeutic of isolated infective endocarditis of
the tricuspid valve].
AB - We reviewed the records of patients admitted to our centre with the diagnosis of
isolated tricuspid valve infective endocarditis and analysed the clinical
presentation, etiopathogenic agent, echocardiographic features and therapeutic
approach, namely the indication for cardiac surgery. Between 1988 and 1996, 11
cases of confirmed tricuspid valve endocarditis were identified, corresponding to
5% of the cases of endocarditis admitted to our centre in the same period. A
predisposing factor was found in ten of the patients, half of them intravenous
drug addicts and Staphylococcus aureus was the most frequent agent isolated.
Fever and pleuro-pulmonary manifestations were predominant clinical features.
Transthoracic echocardiography had a crucial role in the diagnosis and
transesophageal echocardiography was important to characterize vegetations. Four
patients underwent cardiac surgery, for persistent infection. In two cases,
excision of the vegetations and ring annuloplasty was performed. In two patients
not addicted to drugs, the tricuspid valve was replaced with a bioprosthesis,
since the extension of the damage to the valve did not allow repair. One patient,
with early endocarditis of a tricuspid bioprosthesis died before surgery was
attempted.
PMID- 9656767
TI - [Conn's syndrome. Primary hyperaldosteronism caused by adrenal gland adenoma].
PMID- 9656768
TI - [Rationale for the pharmacologic treatment of cardiovascular diseases].
AB - In what concerns the appropriate usage of drugs in the treatment of
cardiovascular diseases, this paper provides a set of concepts and guidelines to
aid the clinician in the choice of drug, the appropriate dose, the form of
administration and the assessment of results. Therefore, the concepts of
pharmacokinetics and pharmacodynamics which condition the administration regimen
are also presented, as well as the notions of bioavailability, halflife and
clearance in the light of the theory of the two compartments, quoting examples in
the various pharmacologic groups currently used in cardiology. The main forms of
administration and the respective indications are analysed and the concepts of
tolerance, hypersensitivity and intolerance to a drug are also discussed. The
importance of the major clinical trials in the assessment of the effects of drugs
is supported, which consubstantiates the clinical decision based on scientific
evidence. The notions of the efficacy and benefit of a treatment are presented,
with examples of some recent clinical trials. The paper ends with a reference to
the drug surveillance and cost-benefit studies.
PMID- 9656769
TI - [Coronary angiography in the assessment of the probability of coronary artery
disease].
PMID- 9656770
TI - Cardiopulmonary exercise testing identifies low risk patients with heart failure
and severely impaired exercise capacity considered for heart transplantation.
PMID- 9656771
TI - [Impossibility to foresee ischemic recurrences after myocardial infarction].
PMID- 9656772
TI - [Diastolic left ventricular dysfunction related with exercise in heart failure].
PMID- 9656773
TI - [Chronic granulocytic leukemia (Ph+): among yesterday's myeloproliferative
syndromes, today's chronic myeloid leukemias, and tomorrow's mature-element
monocellular myelopathies].
PMID- 9656774
TI - [The Philadelphia chromosome: from the gene to therapeutic methods].
PMID- 9656775
TI - [Interferon alpha in the treatment of chronic myeloid leukemia. Promises,
realities, and perspectives].
PMID- 9656776
TI - [Allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia].
PMID- 9656777
TI - [Autologous hematopoietic stem cell transplantation in chronic myeloid leukemia].
PMID- 9656779
TI - [Advancing lung diseases--an epidemic which needs more alertness].
PMID- 9656778
TI - [Cellular immunotherapy in chronic myeloid leukemia].
PMID- 9656780
TI - [Stop treatment when the brain is dead].
PMID- 9656781
TI - [Poliomyelitis--the beginning of the end].
PMID- 9656782
TI - [The usefulness of clinical pulmonary examination in the diagnosis of bronchial
obstruction].
AB - In order to evaluate the usefulness of physical examination of the chest in
diagnosing bronchial obstruction, 11 doctors recorded their findings in 692 adult
chest patients. Spirometry was carried out after the physical examination. Two
categories of patients were selected; patients with known or suspected pulmonary
disease (n = 209) and patients who had consulted their doctors for other reasons
(n = 483). Bronchial obstruction defined as either FEV1 < 70% predicted or FEV1 <
70% of FVC, was found in 74 of the "pulmonary patients" and 55 of the "non
pulmonary" patients. In the group of patients with bronchial obstruction, a
pathological or less certain sign of chest disorder was found in 91% of the
"pulmonary" patients, and in 42% of the "non-pulmonary" patients (p < 0.000001).
Strenuous respiration was registered in 41% of the "pulmonary" patients with
bronchial obstruction, whereas sensitivity was only 2% in the other group. Where
there were two or more pathological chest findings, the risk of bronchial
obstruction occurring was 66% among the "pulmonary" patients, as opposed to 37%
in the "non-pulmonary" group. Physical examination of the chest appeared to be
very useful in the detection of bronchial obstruction in patients with pulmonary
symptoms, but of limited value in screening for bronchial obstruction.
PMID- 9656784
TI - [Urinary incontinence in women in a geriatric ward].
AB - 101 elderly female patients participated in a multidisciplinary programme for the
diagnosis and management of urinary incontinence. Their median age was 81 years.
83 patients had been incontinent for more than 12 months. In only 23 patients was
incontinence recognised as a problem prior to admission, and 69 patients claimed
that they had never received any treatment for their disability. Urge and mixed
incontinence were found to be the most prevalent forms, based on symptoms and
simple measurements. After assessment, one to six measures were implemented for
each patient in order to counteract internal and external causes of incontinence.
The patients were reviewed after 6-8 weeks. 60 patients claimed there was an
improvement, including 20 who described themselves as "much improved", and seven
who had become continent. It is suggested that a hospital stay may provide a
suitable opportunity to undertake primary assessment and treatment of
incontinence in elderly women.
PMID- 9656783
TI - [Medication practice and personal knowledge of the disease among patients with
obstructive lung disease].
AB - 250 patients with obstructive lung disease who had attended an out-patient clinic
were assessed after reporting on individual medication practices and their
personal knowledge of the disease. 56% of the patients reported using two types
of asthma medicine. The use of three, four, and five or more antasthmatica was
reported by 26%, 9% and 5%, respectively. 90% had been prescribed an inhalation
corticosteroid. Of these, one in five reported using it only when required,
whereas in the age group 18-34 years the corresponding figure was one in three
(34%). Regardless of what medication the patients were using, 20% reported that
they often forgot to take it, 20% that they stopped taking it when their asthma
improved, and 38% that they did not think about what time of the day they took
their medicine. These practices of taking medication occurred more frequently in
the young than in older patients. Practices did not vary with either a person's
sex, duration of disease, or the patient's personal assessment of the seriousness
of the disease. Patients with a higher level of education seemed to have greater
knowledge of their disease than those with only secondary education, as was also
the case with nonsmokers compared to smokers.
PMID- 9656785
TI - [The effect of pelvic floor exercise on stress urinary incontinence].
AB - Several randomised controlled trials have shown that pelvic floor muscle exercise
has resulted in a 60-70% improvement or cure rate from stress incontinence. The
aim of the present study was to assess whether these methods could be put into
general use in a physiotherapy clinic in primary health care. 36 women, all with
a diagnoses of stress urinary incontinence, mean age 49 (range 25-67 years),
participated in the study. Before treatment they underwent vaginal examination to
ensure there was proper pelvic floor muscle contraction. Pelvic floor muscle
strength was assessed by vaginal pressure measurement. Urinary leakage was
registered on a 13-item "leakage index", using a 5-point graded scale (1 = never
leakage to 5 = always leakage). The women attended a six-month pelvic floor
muscle exercise programme, training in groups led by a physiotherapist, and
exercising at home with three series of 8-12 contractions a day. 12 patients
reported to be cured, and 12 reported a significant improvement (67% in all).
Five patients achieved some improvement, whereas in another five there was no
change. None became worse. It is concluded that pelvic floor muscle exercises,
under the guidance of trained physiotherapists, may be just as effective in
clinical practice as in randomised controlled trials.
PMID- 9656786
TI - [Penis fracture].
AB - Fracture of the penis is a rare condition caused by blunt trauma to the erect
penis resulting in tearing of the tunica albuginea. The injury occurs mainly
during sexual intercourse or as a result of forceful manipulation. Two cases are
described. Diagnosis is based on the patient's narrative and the clinical
findings. One patient was treated by immediate surgery, while the other was
treated by corrective surgery for his disabling posttraumatic penile deformity.
Based on available literature and our own observations we recommend immediate
surgical repair in order to avoid serious complications.
PMID- 9656787
TI - [Measurement of exhaled nitric oxide. A new lung function test?].
AB - Nitric oxide (NO) is a gas molecule produced endogenously in the lungs. It can be
detected in the exhaled air of animals and humans. Nitric oxide can be generated
in the air passages by a synthase which is induced in several cell types by
exposure to proinflammatory cytokines. Its induction is blocked by
glucocorticoids. An increased concentration of nitric oxide can be found in the
exhaled air of patients with asthma and other inflammatory lung disorders. Gas
analysers for measuring nitric oxide in exhaled air have recently been made
commercially available. The test is non-invasive, simple to perform, and can also
be used in patients with reduced lung function. The method seems to provide a
unique non-invasive means of diagnosing and monitoring inflammation of the air
passages, and in the future the test may become a useful tool in a clinical
setting. Preliminary recommendations for measurements and technical
standardization have recently been proposed by the European Respiratory Society.
PMID- 9656788
TI - [Reflexes in brain-dead patients].
AB - We report on a patient who suffered an acute, extensive intracerebral
haemorrhage, leading to symptoms of cerebral herniation within a few hours. The
clinical diagnosis of brain death was made based on a neurological examination,
and an apnoea test eight hours after the haemorrhage. A few hours later the
diagnosis was changed, as several reflexes reappeared. After six days mechanical
ventilation was withdrawn, as the brain damage was considered so serious as to
render further therapy futile. It was considered unethical to sustain therapy for
a possible organ donation at a later date. A review of relevant the literature,
however, shows that brain-dead patients may exhibit such varying degrees of
autonomic and spinal reflexes as to cause confusion, thus delaying the physician
in making a diagnosis. Often, an opportunity for organ donation is lost. Based on
this review, we believe that our patient was indeed brain dead when the first
diagnosis was made, and that a cerebral angiography should have been performed.
Because organ donation is an important issue, the diagnosis of brain death must
be definitive.
PMID- 9656789
TI - [Adverse effects of zopiclone].
AB - In 1994 zopiclone (Imovane), a cyclopyrrolon, was introduced in Norway as a new
kind of hypnotic. In 1996 zopiclone had a 26% share of the hypnotic market. This
review of relevant literature has revealed a lack of documentation on the adverse
effects of zopiclone. The similarities between zopiclone and benzodiazepine
hypnotics are more striking than the differences. The bulk of comparative
research has been carried out with triazolam, a drug taken off the Norwegian
market in 1991. With zopiclone there is less inhibition of psychomotor function
the day after intake than with flunitrazepam. Zopiclone causes less subjective
"hangover" than nitrazepam, but there is a similar inhibition of psychomotor
function the day after intake, and in some cases greater addictive potential.
PMID- 9656790
TI - [DNA repair enzymes and their genes].
AB - DNA repair is of fundamental importance for protection of the genetic material
against mutations in an interplay with mechanisms that regulate the cell cycle,
gene expression, and programmed cell death. Defects in DNA repair, or in
processes in tegrated with DNA repair, may give cells a hyper mutable phenotype
that increases the likelihood of mutations in genes controlling cell growth. Two
principally different DNA repair mechanisms are known; (a) direct repair of a
damaged base by a single enzyme without using information from the complementary
strand, and (b) excision repair, in which DNA containing the damage is removed
and replaced by new DNA using DNA repair synthesis. Mechanisms for excision
repair are complex and comprise base excision repair (BER), nucleotide excision
repair (NER), mismatch repair (MMR), and recombination repair. In addition, the
cell has mechanisms for repair of strand breaks. It has recently become clear
that defective MMR is the cause of hereditary nonpolyposis colon cancer (HNPCC),
and probably some 15% of the cases of sporadic colon cancer. There is also
evidence that defective repair may be a primary cause of certain other forms of
cancer.
PMID- 9656791
TI - [Telomeres, telomerase and development of cancer].
AB - The chromosome ends, telomeres, shorten during each cell division due to the
inability of DNA polymerase to replicate the ends of linear chromosomes. The
telomere length serves as a clock determining the remaining replicative capacity
of the cell. After 50-100 doublings, the cell becomes senescent. Rarely, a cell
overcomes the senescence blockade, and eventually becomes immortal. Cellular
immortalisation is almost always accompanied by the expression of the enzyme
telomerase, which synthesises telomeric DNA. Telomerase is present in
approximately 85% of malignancies. The detection of telomerase activity in cancer
cells represents a possible cancer diagnostic and prognostic tool, and telomerase
inhibition may become a novel therapeutic strategy in cancer patients.
PMID- 9656792
TI - [Is it justifiable to put the destiny of scholarship recipients into the hands of
their supervisors?].
PMID- 9656793
TI - [Is treatment of lung cancer characterized by nihilism?].
PMID- 9656795
TI - [Traditional and modern medicine in Ngami].
PMID- 9656794
TI - [Mix-up of drugs].
PMID- 9656796
TI - [Transcendental mediatation, stress reduction and hypertension].
PMID- 9656798
TI - [Increased danger for accidental nuclear war].
PMID- 9656797
TI - [Do house mites eat plastics--or what?].
PMID- 9656799
TI - [Do physicians have better sight than others?].
PMID- 9656802
TI - [The tobacco industry--major enemy of health care].
PMID- 9656803
TI - [Research results and discoveries--who owns what?].
PMID- 9656804
TI - [Quality assurance of back surgery].
PMID- 9656805
TI - [Quality assurance of back surgery. A follow-up of 350 patients treated for
sciatica by means of survival analysis].
AB - 350 patients underwent a follow-up 2-16 years after back surgery. The aim was to
find quality indicators, such as frequency of complications, recurrences and
reoperation, in addition to establishing postoperative status and patient
satisfaction. The complication rate was 9.7%. Most complications were not
serious, and there was no mortality. We found a cumulative recurrency rate of 18%
and a cumulative reoperation rate of 12%. Women had significantly better long
term results than men, psychosocial problems being a strong negative predictor.
Questionnaires revealed that 76% of the patients were satisfied, whereas 22% were
not. Postoperatively, 59% reported a persistent, but usually slight back problem.
PMID- 9656806
TI - [Paresis of the superior oblique eye muscle].
AB - Congenital or acquired palsy of the superior oblique eye muscle presents a
clinical picture which is consistent and recognizable. The diagnosis is based
upon two clinical findings: hypertropia of the affected eye with a greater than
normal vertical deviation in adduction, and an increase of the hypertropia when
tilting the head towards the affected side (positive Bielschowsky test). In the
majority of cases the dominant feature of the clinical picture is overreaction of
the ipsilateral inferior oblique. We have retrospectively examined 22 patients
with superior oblique palsy who underwent surgery. Median follow-up time was
three months. 20 (91%) of the patients were operated primarily by performing a
recession of the ipsilateral inferior oblique muscle. Additional surgery had to
be performed on five patients. The final postoperative examination showed the
result to be a success in 19 (86%) of the patients, judged on relief of symptoms
and objective measurements. We conclude that in the majority of cases surgical
treatment of superior oblique palsy by recession of the ipsilateral inferior
oblique gives good results.
PMID- 9656807
TI - [Use of antipsychotic drugs in a long-term care institution. Experiences with
implementing clinical guidelines].
AB - Anti-psychotic drugs (neuroleptics) are useful for treating psychoses. However,
non-psychotic patients, particularly patients with a deviant behaviour pattern,
are often also treated with anti-psychotic drugs. The drugs may induce serious
side-effects and should only be used on strict indications and at the lowest
possible dosage. In a nursing home for deaf people with additional handicaps we
introduced clinical guidelines for the use of anti-psychotic drugs and recorded
their use during a two-year period. We found there was a reduction in the number
of patients taking anti-psychotic drugs (from 32/54 to 26/54, p = 0.03), as well
as a decrease in dosage per user (from median 2.4 mg to 1.7 mg equivalents of
haloperidol, p = 0.05). Both the number of patients who were given depot
injections and the number of different anti-psychotic drugs per patient were
reduced. We conclude that it is possible to reduce the use of anti-psychotic
drugs in institutions where long-term care is provided for disabled people.
PMID- 9656808
TI - [Forensic psychiatric examinations of the mentally retarded].
AB - 3,343 forensic psychiatric examinations were recorded in Norway from 1980 to
1996. 294 patients were diagnosed as mentally retarded. The annual number of
mentally retarded persons increased during the observation period, but the
relative percentage remained stable. The majority of the retarded persons being
discussed had been charged with sexual felony, and some with arson. About half
had previous convictions. Few had problems with alcohol or other intoxicants.
Every fourth retarded person examined was considered not only to be mentally
retarded, but also to suffer from other psychiatric disorders. We discuss to what
extent deinstitutionalization of retarded persons and the accompanying social
isolation they experience could contribute to the increase in maladaption and
criminal behaviour. It is stressed that many of the sexual felonies may be
explained by the fact that the mentally retarded are mentally immature.
PMID- 9656809
TI - [Depression and Down syndrome].
AB - Emotional and behavioural disorders are frequent complications of mental
retardation that often go unrecognised or untreated. We describe a 13-year old
girl with Down's syndrome and depressive illness who responded well to paroxetin.
The importance of organizing comprehensive health provision for children with
mental retardation in a way that focuses both psychiatric and physical illness is
emphasised.
PMID- 9656810
TI - [Venous thromboembolism in connection with physical restraint].
AB - A 29-year old man was admitted to an emergency psychiatric ward because of
exacerbation of a chronic paranoid schizophrenia. He was restrained after
arrival, and seven days later a deep venous thrombosis and a pulmonary embolism
were diagnosed. No haematological predisposing factors (coagulation inhibitor
deficiency, activated protein C resistance, or antiphospholipid antibodies) were
identified, except for a questionable borderline increase of the fibrinolysis
inhibitor PAI-1, and combined type II hyperlipidaemia. During the last 15-20
years, there has been a considerable reduction in the use of restraint and
seclusion in Norway. The use of seclusion and restraint may be effective in
preventing injury and reducing agitation, but these procedures may also have
harmful physical, and in particular psychological side-effects. To our knowledge,
this is the first report to demonstrate an association between venous
thromboembolism and physical restraint. Immobilisation is a well-known risk
factor for thrombophlebitis, and special attention should be paid to this problem
on psychiatric wards. However, until more is known about thrombosis in relation
to restraint, it is not advisable to recommend prophylactic treatment of
thrombosis.
PMID- 9656811
TI - [Children and adolescents with ulcerative colitis and Crohn disease].
AB - The diagnosis and treatment of children and young people with ulcerative colitis
and Crohn's disease follows the same guidelines as for adults, but several
important and unique problems related to the diseases in young age groups deserve
attention. Since ulcerative colitis and Crohn's disease are relatively rare at a
young age, there is often a lack of awareness among people in general, parents
and general practitioners. There is therefore often an unnecessarily long delay
before the young patient is seen by a general practitioner and then referred to a
specialist centre where the diseases can be properly diagnosed, evaluated and
treated. Chronic gastrointestinal symptoms caused by inflammatory bowel disease
at an age where physical and mental growth are at a peak could result in serious
negative effects not only on young patients' physical and mental development, but
also on their self-esteem. The diseases adversely affect the quality of life of
many young patients and their families and are a source of anxiety, emotional,
behavioural, and psychological morbidity. Patients' organisations can help by
providing additional information and support through special groups for young
patients with inflammatory bowel disease.
PMID- 9656812
TI - [Can we rely on self-reported smoking habits?].
AB - The reliability of self-reporting on smoking habits has been evaluated by
comparing the reported smoking habits with the concentration of serum
thiocyanate, which is higher in smokers than in non-smokers and increases with
increasing cigarette consumption. When a smoker stops smoking, the level of serum
thiocyanate decreases and falls to the level observed in non-smokers after about
one month. When the questions asked about smoking were neutral, the reported
smoking habits were generally reliable. However, in cases where the questions
asked and the interview situation could be regarded as unpleasant, the reported
smoking habits were not always correct. Some smokers underreported the number of
cigarettes they smoked on a daily basis and some of them denied smoking
altogether.
PMID- 9656813
TI - [Who gives up smoking? Results from the health surveys in Finnmark in 1977/78 and
1987/88].
AB - In order to develop effective smoking cessation programmes, it is important to
understand why people stop smoking. This study is based on data from two
population-based health surveys carried out in the northernmost county of Norway
in 1977-78 and 1987-88. 6,254 men and 6,404 women smokers participated in the
survey. For both surveys questionnaires were used to collect information on
smoking habits, sociodemographic variables, various diseases, symptoms, health
related behaviours, and social network. Ten years later 19.3% of the men and
16.0% of the women had stopped smoking. The primary factors for giving up were: a
short history of smoking, older age, having non-smoking family and friends, and
acquiring a smoking related disease during the period. Health promoting
behaviours, such as low consumption of coffee, alcohol, butter and margarine,
also increased the chances of giving up smoking. Developing smoking related
symptoms, such as a morning cough, or coughing up mucus in the mornings,
predicted continuous smoking. Future health promotion programmes should be
targeted at young smokers and persons with smoking related diseases; and efforts
should probably be directed towards lifestyle with the aim of modifying general
attitudes to health.
PMID- 9656814
TI - [The use of tobacco and smoking habits--is Norway lagging behind?].
AB - A comparative analysis of smoking habits, based on data from three different
sources, shows that the present level of tobacco consumption in Norway is at a
mid-Nordic level, but lower in a European perspective. There has been a 25%
decline in per capita consumption of tobacco since the mid-1970s, and the
decrease has been most pronounced during the 1990s. The current rate of decline
is the same as in the other Nordic countries. The prevalence of smoking among men
is at present lower in Norway than in most European countries outside the Nordic
ones. Since the mid-1950s, the prevalence of daily smoking among Norwegian men
has decreased from approximately 70% to 35% in 1997. However, within the last ten
years the decline has levelled out and smoking among men has been stable in
recent years. Smoking among women is more widespread in Norway than in most
European countries. The number of female smokers reached a peak around 1970.
Since the 1970s, the prevalence of smoking among women has been stable. The
prevalence of daily smoking in the age-group 16-24 years is currently at a mid
European level. However, the decline observed during the late 1970s and the first
half of the 1980s does seem to have levelled out during the 1990s.
PMID- 9656815
TI - [Passive smoking and risk of cancer].
AB - During the last two decades there have been frequent discussions as to whether
passive smoking causes cancer, or not. It is difficult to carry out satisfactory
studies on this issue, partially because any increased risk of cancer seems
modest. The tobacco industry has not only attempted to make the public aware of
studies which conclude that passive smoking is harmless, but it has also tried to
keep alive the discussion as to whether exposure to passive smoking is harmful,
or not. A large number of studies has been carried out on the possible impact
passive smoking may have on the risk of lung cancer, and it seems justifiable to
conclude that passive smoking does increase the risk of this type of cancer. For
other types of cancer too few studies have been performed to draw any firm
conclusions.
PMID- 9656816
TI - [Molecular biology diagnosis of sarcoma].
AB - Sarcomas are a heterogeneous group of malignant tumours, primarily in connective
and supportive tissues, that can be difficult to distinguish from other tumour
types. Recent knowledge of gene rearrangements resulting from specific
translocations in several groups of sarcomas now enables the molecular diagnosis
of these subtypes. Increasing knowledge of molecular defects that may be of
importance to therapy response and prognosis may in the future become important
tools in the clinic, although these tumours are relatively rare, making it
difficult to investigate large numbers of comparable groups of patients.
PMID- 9656817
TI - [Diagnostic molecular biology in prostatic cancer].
AB - Studies of molecular genetic changes in prostate carcinomas are slowly improving
our understanding of the biological process which leads to a normal prostate
epithelial cell becoming an adenocarcinoma cell with invasive and metastatic
properties. Carriers of germ-line mutations in still unidentified prostate cancer
susceptibility genes, one of which has been localised to chromosome arm lq, seem
to be particularly prone to develop the disease. The susceptibility genes have to
be identified and the effects of carrier detection evaluated before genetic
testing for prostate cancer predisposition can be performed in a clinical
setting. The identification of specific molecular genetic changes in prostate
carcinomas may become clinically useful diagnostic and prognostic tools. An
improved understanding of the molecular genetic mechanisms underlying the
development of prostate cancer may eventually yield novel therapeutic strategies,
attacking specific genetic changes in the prostate carcinomas.
PMID- 9656818
TI - [Diagnostic molecular biology in solid tumors--thyroid gland].
AB - Thyroid cancer is not a common disease. It includes tumour types of great
diversity in clinical course and molecular basis. Mutations of TSH-receptor,
rearrangements of ret proto-oncogene, and altered expression of other tyrosine
kinase growth factor receptors are characteristics of the follicular neoplasias
and papillary carcinomas, while undifferentiated tumours harbour p53 mutations.
Knowledge acquired to date has led to an increased understanding of thyroid
growth and tumour development, but it has had no significant impact on diagnostic
and treatment measures. On the other hand, the C-cell derived medullary
carcinomas include familial cases where identification of germ-line ret mutations
provides the basis for prophylactic thyroidectomy in affected individuals.
PMID- 9656819
TI - [The psychiatric record].
PMID- 9656820
TI - [Aimed health check-ups can be justified].
PMID- 9656821
TI - [California Proposition 99--an example to follow?].
PMID- 9656822
TI - [Estrogen replacement is better than alendronate].
PMID- 9656823
TI - [Causes of social inequality in relation to health].
PMID- 9656824
TI - [Self perception of the elderly].
PMID- 9656825
TI - [New Danish and international rules on research ethics].
PMID- 9656826
TI - [Treatment of pain via a cervical epidural catheter].
AB - Cervical epidural anaesthesia (CEA) is a method suitable for regional anaesthesia
of the upper extremity. CEA seems useful for postoperative pain relief after
surgery in the shoulder region or both upper extremities, especially when the
postoperative pain relief must be long lasting (days), and when it is desirable
that the patient be able to actively move his affected joints during
rehabilitation. Potential side effects of the method are respiratory- and
haemodynamic changes. Thus, CEA is inappropriate for patients with severe
respiratory disease, and in patients for whom extensive sympathetic block may
prove disastrous (e.g. congestive heart failure, hypovolaemia).
PMID- 9656827
TI - [New techniques in neurosurgery].
AB - Society demands for exactness and low complication rates of surgical treatment
are high. Surgical training in the apprentice manner has been significantly
reduced in Denmark since 1981 and e.g. the ability to visualize in three
dimensions among younger neurosurgeons has diminished. Computer technology now
makes it possible to create 3-D images that with incorporation of functionality
leads to a faster and better understanding of neuroanatomy. In addition--for the
sake of precision--true robotic instrumentation and navigational instruments have
been introduced. The technological investments are compensated by reduced costs
due to operative complications. A prerequisite for these developments are a close
collaboration between medical doctors and engineers, keeping the respect for
humanity intact. A survey of developmental areas in the neurosurgical techniques
of today is given.
PMID- 9656828
TI - [Juvenile neuronal ceroid lipofuscinosis].
AB - Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are
characterized by an abnormal accumulation of lipopigment in neuronal and
extraneuronal cells. The diseases can be differentiated into several subgroups
according to age of onset, the clinical picture, neurophysiological and
neuropathological abnormalities and ultrastructural studies documenting different
profiles of the lipopigment. Several eponyms have been used in the designation of
the diseases. Latest, an international designation abbreviated CLN has been
recommended, with the addition of figures according to the subtypes. The most
common type in Denmark is CLN3, also called Spielmeyer-Vogt's disease. The
incidence is 1.6 per 100,000. It is characterized by slowly progressing
behavioral and visual symptoms that start when the child is about four to nine
years old. During the second decade of life, the disease is accompanied by
seizures and severe psychomotor deterioration. Most patients die before the age
of 30 years. Recently, it has been shown that this type of CLN disease is due to
a mutation in a gene located on chromosome 16 (16p 12.1). A brief description of
the other subtypes of CLN is given.
PMID- 9656829
TI - [Enzyme substitution in Gauscher disease].
AB - Gaucher's disease is the most frequent inherited lysosomal storage disorder,
displaying hepato-splenomegaly, thrombocytopenia, anaemia, and bone pain as
characteristic features. Substitution with the modified enzyme alglucerase has
revolutionized the treatment and prognosis of Gaucher's disease. Treatment in
general and current trends in enzyme substitution therapy in particular are
discussed.
PMID- 9656830
TI - [Sequelae after polio--a review].
AB - Poliomyelitis has almost been eradicated world-wide, but during the last decades
polio survivors have noted new problems: late effects of polio and post-polio. In
Denmark, 7-8000 polio survivors are disabled by poliomyelitis. Late effects of
polio, defined as onset of new symptoms decades after the acute poliomyelitis,
include fatigue and overuse muskuloskeletal problems. Post-polio is a sub
category of the late effects of polio and related to impaired neuro-muscular
function with unexpected onset, which is not caused by the patient's age. Post
polio is a clinical diagnosis and cannot be verified by a definitive test. The
dysfunction of the muscles is caused by loss of motor neurones and reduced
neuromuscular reserve capacity, in combination with a disturbed balance between
the ongoing reinnervation and denervation at the expense of the reinnervation.
Many polio survivors suffering from late effects of polio have a need for
multidisciplinary rehabilitation, physiotherapy, reconstruction of orthosis,
social counselling, modifications to the home and individual aids.
PMID- 9656831
TI - [Neurosurgical treatment of trigeminal neuralgia. A comparative study of alcohol
block, neurectomy and electrocoagulation].
AB - The objective was to assess the present condition of patients previously treated
with neurosurgical procedures for trigeminal neuralgia (TN). Between 1976 and
1991, 383 patients were treated for TN at the Department of Neurosurgery,
Hvidovre Hospital. The latest surgical intervention performed was radiofrequency
coagulation (64%), neurectomy (18%), alcohol block (16%), trigeminal tractotomy
(1%), and microvascular decompression (1%). Questionnaires were sent to 316
patients treated neurosurgically for trigeminal neuralgia during the 16 year
period. After radiofrequency coagulation, neurectomy and alcohol block, 83, 51
and 42% respectively experienced a pain free postoperative period. At present 49,
17 and 18% were without pain and 33, 21 and 36% had less pain compared with the
preoperative state. Sequelae were described in 65, 57 and 49% of the patients.
The four most common sequelae were hypaesthesia, paraesthesia, eye complaints,
and dysaesthesia. If relevant pharmacotherapy has been tried without benefit,
radiofrequency coagulation may still be considered as a treatment of trigeminal
neuralgia.
PMID- 9656832
TI - [Prolapsed cervical intervertebral disk in professional drivers in Denmark 1981
1990].
AB - The aim of this study was to estimate the risk of being hospitalized due to
prolapsed cervical interverteral disc among male professional drivers in Denmark.
A cohort consisting of all economically active persons in Denmark, identified
January 1981, gives information on the most important occupation during 1980. The
cohort was followed for ten years. Additional data on occupational exposures were
extracted from a national survey. Occupational groups such as bus and taxi-cab
drivers were found to have an increased risk, of cervical prolapse as did the
group of professional drivers as a whole.
PMID- 9656833
TI - [The prognostic value of thrombocytosis in patients with primary lung cancer].
AB - The prognostic information provided by platelet counts was studied in 1115
patients with primary lung cancer and in 550 control patients with benign lung
disorders. Patient records were retrospectively reviewed regarding histological
tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of
thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was
32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage
(p < 0.0001). Patients with thrombocytosis had a shorter survival than patients
with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short
survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001).
The platelet count and the frequency of thrombocytosis declined after tumour
resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism.
In conclusion, thrombocytosis is a clinically significant prognostic indicator
regarding survival in patients with primary lung cancer.
PMID- 9656834
TI - [Surgery for phimosis with Plastibell. A follow-up study].
AB - Fifty-three boys were interviewed 11 years (9-14 years) after an operation for
phimosis using the Plastibell technique. The interview concentrated on the
cosmetic result, sexual function and late complications. Seventeen patients (31%)
experienced cosmetic complications, and 11 patients (21%) claimed to have
experienced psycho-social problems due to the appearance of the penis after the
operation. Nonetheless an overall of 44 patients (83%) were fully
satisfied/satisfied with the cosmetic result. Four patients (8%) claimed to have
pain or discomfort on erection or intercourse. One patient (2%) was re-operated
three years after the primary operation because of a recurrence of the symptoms.
Overall 48 patients (91%) were fully satisfied or satisfied with the result after
the operation. In conclusion we find the Plastibell procedure to be a safe and
reliable method in treating phimosis. There are some minor technical pitfalls
that have to be addressed in learning the technique, but performed in trained
hands, the technique offers a very high satisfaction rate at long term follow-up.
PMID- 9656835
TI - [Indications for cataract surgery in Denmark in 1980 and 1992. Results from the
Danish Cataract Surgery Outcomes Study].
AB - In Denmark the number of cataract extractions has increased to 350% from 1980 to
1991. During the same period the elderly population at risk has only increased to
117%, and thus cannot account for the large increase in the number of
extractions. In order to investigate whether more comprehensive clinical
indications could be a possible explanation, we compared pre-operative visual
acuity and visual impairment in two consecutive samples of Danish cataract
surgery patients obtained in 1980 (n = 73) and in 1992 (n = 270). Criteria for
inclusion were similar and both samples were representative for the whole
country. During the period mean pre-operative visual acuity increased from 0.04
to 0.16 in the eye enlisted for surgery (p < 0.001). Visual functional impairment
could be compared by using the same questionnaire for patient interview in 1992
as was used in 1980. In 1992, the degree of impairment was significantly less for
reading, outdoor orientation and self care activities. A change in surgical
threshold or clinical indications for surgery appears to be a major contributing
factor to the large increase in surgical rates.
PMID- 9656836
TI - [Gaucher disease type 1--therapeutic results of enzyme substitution].
AB - Gaucher's disease is the most common inherited lysosomal storage disorder,
displaying hepato-splenomegaly, thrombocytopenia, anaemia and bone pain as
characteristic features. Substitution therapy with a modified enzyme alglucerase
has revolutionized the treatment and prognosis of Gaucher's disease. The first
Danish patients treated with alglucerase are reported.
PMID- 9656837
TI - [Angiotensin-converting enzyme inhibitor dosage in chronic heart insufficiency].
PMID- 9656838
TI - [The possibility of driving under influence among traffic offenders. II].
PMID- 9656839
TI - [Serotonin antagonists in the treatment of postoperative nausea and vomiting].
PMID- 9656841
TI - Occlusal vertical dimension: what is the controversy?
PMID- 9656840
TI - An esthetic alternative to conventional porcelain-fused-to-metal crowns.
PMID- 9656842
TI - Occlusal vertical dimension: alteration concerns.
AB - This article exposes common myths supported by restorative dentists that serve to
limit our potential for achieving more favorable results. The need to alter
occlusal vertical dimension (OVD) signifies a number of concerns that include:
bite force measurements, rest vertical dimension, effect on temporomandibular
joint loading, effect on tooth loading, and neuromuscular adaptation/stability.
There appears to be sufficient scientific support to conclude that alteration of
OVD can provide a biologically compatible adjunct to treatment. These alterations
can improve dentofacial esthetics, create improved visual proportions in facial
height, and provide an important treatment modality for force management of the
masticatory system.
PMID- 9656843
TI - Facially generated occlusal vertical dimension.
AB - Facial height has a profound effect on attractiveness. Occlusal vertical
dimension (OVD) determines facial proportion at maximum intercuspation and
influences facial dimension at rest. Deficient facial height visibly compromises
optimal facial beauty. This article explores the dependent relationships between
the OVD and facial esthetics, and discusses the role of facial analysis in
determining an optimal OVD.
PMID- 9656844
TI - Vertical facial skeletal dysplasias: the oral surgical connection.
AB - Oral surgery can open new vistas of treatment for patients with vertical
abnormalities of the face, jaw, and teeth. An interdisciplinary approach is
critical, however, incorporating the insights and skills of restorative,
orthodontic, periodontal and surgical practitioners working together as a team. A
complete diagnosis is the key to any successful treatment plan. Because surgery
is instantaneous and relatively irreversible, the treatment team needs to be
aware of the impact of surgical repositioning of the maxilla and mandible on the
other treatment modalities, so the ultimate prosthetic objectives for the patient
may be facilitated and not hindered. The craniofacial complex is more adaptable
to vertical changes than is often realized. When a correct "palate" of therapies
is chosen, the desired results can be achieved despite the complexities of
symptoms and treatment. A desirable result must include optimum function,
stability, and facial harmony.
PMID- 9656845
TI - Are speech-based techniques for determination of occlusal vertical dimension
reliable?
AB - This article describes the most common techniques used for clinical assessment of
occlusal vertical dimension (OVD), and includes a discussion of recently
published data which strongly suggest that techniques based on sibilant sounds
are not as reliable as they are generally regarded to be for the evaluation of
OVD. Assessment and establishment of OVD are sometimes difficult in edentulous
patients, as well as for dentate patients with multiple missing posterior teeth
and/or extensive wear. Techniques based on the use of interocclusal distance and
facial soft-tissue contours, along with techniques based on sibilant sounds, are
discussed. Although absolute scientific support for any technique is lacking, the
careful use of the techniques described in this article, in combination, will
usually result in the establishment of a clinically acceptable OVD for most
patients.
PMID- 9656846
TI - Esthetics and vertical tooth position: orthodontic possibilities.
AB - Throughout the 1990s, esthetic dentistry has become a prominent part of the
treatment protocol of most dentists. Patients have become more conscious of the
benefits of a beautiful smile and are willing to invest time and money to improve
the appearance of their teeth. Many of these patients can be treated with routine
restorative procedures (crowns, composites, laminates) to achieve the desired
results. However, some patients have problems with tooth position that create
significant discrepancies in gingival levels which can compromise the esthetic
result of restorative dentistry. Prerestorative orthodontic therapy can often
resolve these tooth position problems and enhance the esthetic restoration. This
article describes the indication, methods, and results achieved when orthodontics
preceded restorative dentistry in the treatment of various esthetic challenges.
PMID- 9656848
TI - Leadership makes a difference.
PMID- 9656847
TI - The effect of sodium lauryl sulfate on recurrent aphthous ulcers: a clinical
study.
AB - This study measured the incidence of recurrent aphthous ulcers during the use of
dentifrices with and without sodium lauryl sulfate (SLS). A single-blind,
crossover design was used. A statistically significant reduction in recurrent
aphthous ulcers was observed during 2 months' use of SLS-free dentifrice compared
to 2 months' use of the SLS-containing dentifrice. These results support the
results of an earlier independent study, and suggest that use of an SLS-free
dentifrice should be considered for individuals suffering from recurrent aphthous
ulcers.
PMID- 9656849
TI - Clinical evaluation of two carbamide peroxide tooth-whitening agents.
AB - A blinded study was conducted to evaluate the efficacy and safety of a dentist
prescribed, accelerated carbamide peroxide tooth-whitening system. Fifty-one
patients with discolored teeth completed a clinical trial using an overnight
bleaching regimen. One group used an experimental bleaching (whitening) regimen
with 10% carbamide peroxide bleaching paste, and another group used the Colgate
Platinum Professional Overnight Whitening System. The study included an initial 1
week control/compliance phase using a placebo gel, followed by a 1-week active
phase using the assigned bleaching agent. The shade of each participant's
maxillary anterior teeth was evaluated by 2 trained and calibrated evaluators at
the start of the control/compliance phase, the beginning of the active phase, and
days 3, 5, and 7 of the active phase. A value-oriented Vita shade guide with 16
rankings was used to measure color changes, and the number of shade guide units
of change (delta sgu) was calculated. Potential side effects, such as tooth
hypersensitivity and gingival irritation, also were assessed at each recall
examination, as well as recorded by the patients in their daily diaries. At the
end of the 7-day active phase, the mean delta sgu for the group using the
experimental bleaching agent was 7.1 +/- 2.4, and for the Colgate Platinum
Overnight group, the delta sgu was 7.5 +/- 2.2. There were no statistically
significant (p > or = 0.05) differences between the results of both groups at the
0-, 3-, 5-, and 7-day evaluations. After 7 days, the change in shade guide units
for both groups ranged from 3 to 13 units, far exceeding the minimum required
change by the American Dental Association Guidelines (delta sgu = 2 units) for
demonstrating efficacy. There was no statistical difference in the whitening
achieved at day 5 vs. day 7 for either tooth-whitening group. There were no
notable changes in any gingival, bleeding, or plaque indexes for the 50 patients
completing the active phase. The number of days of mild tooth sensitivity during
the active phase was 0.9 +/- 1.3 days for the experimental agent group and 1.1 +/
1.5 days for the Colgate Platinum group.
PMID- 9656850
TI - Principles of speech and their application to dental reconstruction.
PMID- 9656851
TI - Shade selection: problems and solutions.
AB - This article introduces shade selection as an act of communication rather than a
quasi-science that has failed for generations. The use of three simple items: the
Pensler Shield, the Kodak Color Viewing Light Selector Card (P3-180), and a
patient-oriented prescription form solve the major problems in shade selection.
Shade selection must be taught with an understanding of the psychology of vision
and a communication of what you think you see.
PMID- 9656852
TI - Revised endocarditis prophylaxis guidelines: signal of a new era? American Heart
Association.
PMID- 9656853
TI - Dentoalveolar surgical sequelae.
AB - Most general dental practitioners perform dentoalveolar surgery as part of their
practice. Postoperative sequelae can cause great concern for patients and undue
stress for the general practitioner. This article explains the importance of
patient education with regard to these sequelae and discusses standard treatment
modalities the practitioner can employ if they should arise.
PMID- 9656854
TI - The prevention and management of the broken curet.
AB - With repeated sharpening or improper technique, a curet tip may break inside a
periodontal pocket. This creates a problem for the clinician because the tip
usually cannot be seen or felt. This article offers suggestions that can prevent
such breakage. The include instrument selection and application, appropriate use
of force, and proper sharpening. The article also describes a pair of magnetic
instruments that can remove a loose fragment when curet fracture occurs and
explains how the instruments are used.
PMID- 9656855
TI - To tame the pain?
AB - Pain is still one of the most common reasons given by patients for avoiding
dental care. Dental pain was identified as one of the most common pain complaints
a national survey of pain in the US population. Although pain associated with
dentistry encompasses intraoperative pain and pathologic pain as a result of
dental neglect, it is likely that some of the aversion toward dentistry is a
result of pain that occurs in the postoperative period.
PMID- 9656856
TI - An evaluation of the iatrosedative process for treating dental fear.
AB - The iatrosedative process is an interpersonal-cognitive technique by which
fearful patients are calmed by the behavior, attitude, and communicative stance
of the dentist. The process consists of an iatrosedative interview and a clinical
encounter. In our study, 58 fearful dental patients were assigned to 1 of 3
treatment groups. The Corah Dental Anxiety Scale was administered at admission to
the clinic, immediately after the iatrosedative interview or standard interview,
and again after the first and second clinical encounters. Participants who
received the iatrosedative interview had a significantly greater reduction in
dental anxiety after the interview than those who received the standard
interview. After the two clinical encounters, however, the difference in anxiety
reduction between the two groups was not significant. In addition, there was no
significant difference in anxiety reduction between iatrosedative participants
who had the same dentist for both the interview and the clinical encounter and
participants who had different dentists for each part of the study. It is
concluded that an iatrosedative interview is more effective than a standard
dental interview in decreasing anxiety.
PMID- 9656857
TI - Soft-tissue considerations in esthetic reconstruction.
PMID- 9656858
TI - A morphometric analysis of the furcation region of mandibular molars.
AB - This study examined furcation dimensions and morphology in first and second
mandibular molar teeth. One hundred thirty-four extracted human mandibular molars
with divergent roots were selected. Teeth were viewed at 7X magnification on a
dissecting microscope interfaced with a computer equipped with a state-of-the-art
histomorphometry software program. Various aspects of furcation anatomy were
measured and recorded. Data were examined by using analysis of variance for all
paired comparisons. For nonparametric data, the Kruskal Wallis test was used.
Results indicated that 61.94% of buccal and 50.75% of lingual molar surfaces
presented with cervical enamel projections (CEPs), with the highest frequency
noted in second molars. CEPs ranged from 0.98 mm to 1.33 mm, whereas root trunk
heights varied between 2.23 mm and 2.93 mm. Generally, lingual molar surfaces had
longer root trunks when compared to buccal surfaces. Root separation increased by
approximately 0.5 mm at each 1-mm increment apical to the furcal roof. This study
provides new information regarding the furcal anatomy of mandibular molar teeth
and supplements previous reports that suggest the CEP is a common problem which
must be addressed by clinicians when treating molar teeth.
PMID- 9656859
TI - The importance of dentistry in the differential diagnosis of a medical disorder.
AB - This is a case report of a patient presenting to our clinic with a chief
complaint of occlusal changes, but no clear-cut diagnosis of local origin could
be found. The patient later was diagnosed with acromegaly. This rare systemic
disease, caused by a slow-developing tumor of the pituitary gland, induces
changes in various vital organs. Among them is a change in occlusion that can
bring the patient to the dentist first. Dental professionals may be the first
health care providers to see the signs and symptoms of acromegaly, and thus have
the first opportunity to correctly diagnose this serious disease. This case
demonstrates the importance of taking a thorough medical history and making a
careful diagnosis before any dental treatment is recommended or undertaken.
PMID- 9656860
TI - Direct reimbursement.
PMID- 9656861
TI - Using a precision-metered injection system to minimize dental injection anxiety.
AB - In this study, 90% of dental patients reported being at least mildly anxious
about receiving dental injections. A new precision-metered injection system has
been developed that can greatly increase the probability of painless injections
of local anesthetic. Surveys were administered to patients to quantify their
fears of dental injections and to measure the desensitization effect of using the
new injection system. According to survey results, fear levels decreased
significantly when the new technology was used.
PMID- 9656862
TI - Management of the gingival sulcus in fixed prosthodontics: a literature review
and treatment protocol.
AB - This review of the fixed prosthodontics and periodontology literature illustrates
the influence of various factors on the health of the periodontium during and
after fixed prosthodontic treatment. This article describes four categories of
marginal finish lines for fixed prosthodontic restorations relative to the
gingival margin and the epithelial attachment. The management of each category
from both the periodontal and prosthodontic prespectives is also discussed.
PMID- 9656863
TI - The effect of dental rehabilitation on the body weight of children with failure
to thrive: case reports.
AB - Four case reports of children with nursing caries and failure to thrive are
presented. Without regard to the condition of the dentition, the various cases
could be classified as organic, mixed, or nonorganic in etiology. After dental
rehabilitation, all patients exhibited an acceleration of weight velocity that
resulted in weights above the 5th percentile. During the period of observation,
the weight velocity continued to increase with time, consistent with the "catch
up" phenomenon of growth that is observed in nutritionally deprived children.
PMID- 9656864
TI - Root coverage: combined surgical procedures.
AB - A number of surgical procedures have therapeutic goals to restore the gingival
tissue to the level of the cementoenamel junction with attachment of soft tissue
to the previously exposed root surfaces. These procedures are indicated where
esthetic needs, root sensitivity, or shallow carious lesions involve the root
surfaces. Surgical innovations over the past decade have enabled the periodontist
to correct these problems. Case reports of root coverage by combined surgical
procedures are described and presented. These reports illustrate greater
predictability and improved esthetics compared to other surgical possibilities.
PMID- 9656865
TI - Searching for information on the World Wide Web--a guide for dental health
professionals: Part 2.
PMID- 9656866
TI - Comparative clinical evaluation of removable partial dentures made from
impressions with different materials.
AB - Impressions for removable partial dentures (RPDs) should provide an accurate and
detailed record of the teeth and soft tissues. Removable partial denture casts
should be exact replicas of the mouth to ensure that RPD frameworks fit
accurately and are fully adjusted to oral structures. A comparative clinical
evaluation was performed on the oral fit of RPDs made from impressions with
either irreversible hydrocolloid (alginate) or condensation silicone. The
difference between the two groups was found to be statistically significant.
PMID- 9656867
TI - Two new schemes for classifying propagating cracks in human tooth structure.
AB - Currently, the dental profession has no comprehensive classification method or
scheme to identify the many types of propagating cracks in human tooth structure.
This article presents two new and practical classification systems that encompass
numerous types of cracks. The first is the more simplified--the Surface and
Position Classification System. The second and more comprehensive system is the
Directional Crack Propagation System.
PMID- 9656868
TI - Thermology and facial telethermography. Part I: History and technical review.
AB - This paper is a review of historical trends and technical advances in measurement
of skin temperature. Most biochemical processes generate heat which must be
dissipated. Skin is the major route for heat dissipation using blood as the heat
exchange fluid. Skin temperature is an indicator of aberrations in metabolism,
hemodynamics or in neuronal thermoregulatory processes. Since most of the heat
dissipation of skin is by infrared blackbody emission, skin temperature should be
measured without contact by monitoring the emitted infrared radiation. This has
been the basis of telethermography. Recent advances in computing technology
combined with advanced infrared sensor technology has led to the development of
dynamic area telethermometry (DAT) which promises to be as an important new
quantitative method to analyse the pathophysiology of thermoregulatory processes.
PMID- 9656869
TI - Thermology and facial telethermography: Part II. Current and future clinical
applications in dentistry.
AB - Selected clinical applications using thermal imaging as an aid in dentistry are
reviewed. Facial skin temperature can easily be measured in a clinical setting,
without direct skin contact, by monitoring the emitted infrared radiation. This
is the basis of static area telethermography (SAT) and dynamic area
telethermography (DAT). SAT has recently been shown to be of help to the dentist
in (1) the diagnosis of chronic orofacial pain, (2) as a unique tool in
assessment of TMJ disorders, (3) as an aid in assessment of inferior alveolar
nerve deficit, and (4) as a promising research tool. DAT, recently made possible
by advances in computing technology combined with advanced infrared sensor
technology, extracts quantitative information about hemodynamic processes from
hundreds to thousands of digital thermal images of the affected facial areas,
measured and collected within less than 3 min. DAT has promise of offering a
better insight into aberrations of the neuronal control of facial skin perfusion
and aiding our understanding of the correlation between orofacial pain and facial
thermal abnormalities. This promising new insight may help in the management of
orofacial pain.
PMID- 9656870
TI - The influence of radiographic exposure factors on the diagnosis of occlusal
caries.
AB - OBJECTIVES: To assess the impact of variations in radiographic density on
occlusal caries diagnosis and observers' diagnostic strategy. METHODS: Three
series of radiographs of 60 extracted molars were examined by nine dental
students and caries diagnosed using a five point confidence-rating scale. Film
density in each series was varied by varying exposure time: 1 s (high density),
0.4 s (medium density) and 0.067 s (low density). The 'true' diagnoses were
obtained by stereomicroscopy. Diagnostic quality was measured with ROC analysis
as Az. RESULTS: The difference in Az, values between the low and medium density
series was statistically significant. The sensitivity and the specificity values
for students' diagnoses in outer third of dentine were 85% and 50% for the high
density series, 76% and 56% for the medium density series and 42% and 77% for the
light series. CONCLUSIONS: Occlusal caries was diagnosed best from the darkest
radiographs. Specificity was higher with light radiographs but sensitivity
increased with density. Therefore underdiagnosis is more frequent with light
radiographs, while overdiagnosis occurs more often with dark. The awareness of
these effects could be an important guideline in adjusting the density of digital
images.
PMID- 9656871
TI - The effects of restorative material and location on the detection of simulated
recurrent caries. A comparison of dental film, direct digital radiography and
tuned aperture computed tomography.
AB - OBJECTIVES: To explore the effects of restorative material and lesion location on
the detection of recurrent caries using intra-oral film, direct digital
radiography and unprocessed and iteratively restored tuned aperture computed
tomography (TACT) images. METHODS: An in vitro model with simulated lesions in
half the surfaces studied was used. Lesions of varying sizes were created at
either the intersection of the facial or lingual wall and the gingival floor or
on the gingival floor midway between the facial and lingual walls in the proximal
boxes of 24 molar teeth with MOD inlay preparations that had been restored with
amalgam, radiopaque composite or radiolucent composite. RESULTS: Sensitivity and
specificity values based on restoration were: amalgam: 59 and 87%; radiopaque
composite: 68 and 78%; radiolucent composite: 36 and 93%; based on lesion
location, mid-cervical floor region: 51 and 97%; point angle region: 44 and 90%;
based on imaging modality, film: 40 and 85%; digital: 44 and 76%; unprocessed
TACT slices: 50 and 87%, iteratively restored TACT images: 83 and 96%.
Iteratively restored TACT images had the best intra- and inter-reader agreement.
CONCLUSIONS: The use of restorative materials with a density approximating that
of enamel is more effective for the detection of recurrent caries. Lesions
located at the buccal point angle or mid-gingival floor are more easily detected
than at the lingual point angle region. The sensitivity and specificity of TACT
and iteratively restored TACT images were superior to those of film and direct
digital images.
PMID- 9656872
TI - Panoramic radiographic patterns of the infraorbital canal and anterior superior
dental plexus.
AB - OBJECTIVE: To describe and classify the presentations of the infra-orbital
canal/groove (IOC/G) complex and anterior superior dental plexus (ASDP) on
panoramic radiographs. METHODS: The frequency of occurrence and variations in
appearance of the IOC/G were determined on 246 random panoramic radiographs. A
classification system consisting of Types I, II and III was developed to describe
the radiographic patterns of the IOC/G. RESULTS: Two hundred radiographs (81.3%)
demonstrated evidence of the IOG/C. The most frequent appearance of the IOC was
Type III (44.75%) closely followed by Type I (42%) and Type II (13.25%), with
only minor differences in prevalence between right and left sides. Sixty one
percent were bilateral. Radiologic evidence of the ASDP was noted in 29% of
radiographs demonstrating an IOG/C with 12% of cases being bilateral. Three
distinct radiographic patterns of the anterior superior dental plexus (ASDP) were
also observed. CONCLUSION: A classification of the appearance of the IOC/G and
ASDP on panoramic radiographs has been presented.
PMID- 9656873
TI - Reduction in size of digital images: does it lead to less detectability or loss
of diagnostic information? .
AB - OBJECTIVES: To analyse the effect of reduction in size of digital images on
diagnostic outcome. METHODS: A series of 100 Visualix III (Gendex Dental Systems,
Milano, Italy; Dentsply, Des Plaines, IL, USA) images was made of size 10 and 15
endodontic files in upper and lower (pre)molars. Three forms of image were
created: (a) the original images, (b) reduced to one-half (containing one-quarter
of the information of the original, and (c) zoomed-in, half-size images
(magnification 2:1; original image size but with only one-quarter of the original
information). Seven radiologists were asked to rate the position of the tip of
the file, using a five-point confidence scale. ROC data were analysed by means of
MANOVA statistics. RESULTS: A significant difference was found between the three
image modalities for both size 10 (P < 0.005), and size 15 (P < 0.021) files.
CONCLUSIONS: Reduction in size of digital images may cause less detectability as
well as loss of diagnostic information.
PMID- 9656874
TI - An evaluation of periapical radiography with a charge-coupled device.
AB - OBJECTIVES: To compare the standards of periapical radiography with a CCD-image
receptor with film. METHODS: Three radiography technicians exposed a total of
fifty teeth from all areas of the jaws using either size 1 or size 2 film and the
Sidexis (Siemens, Bensheim, Germany) direct digital dental radiography system
with the appropriate film holders. Image quality was assessed by two dental
radiologists for nine individual criteria and overall, on a three-point scale.
RESULTS: There was a significant difference between film and sensor exposures (P
< 0.014). Six per cent of dental films required retakes compared with 28% with
the sensor. CONCLUSION: Periapical radiography with a CCD sensor leads to more
errors and thus more retakes than conventional film.
PMID- 9656875
TI - Densitometric evaluation of four radiographic processing solutions.
AB - OBJECTIVE: To determine the performance of different processing solutions using
an automatic processor for dental radiography. STUDY DESIGN: One brand of dental
X-ray film (Minimax, Chicago, IL, USA) was developed in an automatic processor
using four different brands of processing solution: Megasan (MGS, Megasan,
Ankara, Turkey), (HAC, Ankara, Turkey), Fuji (Fuji Medical, Hacettepe Cedex,
France) and RP X-Omat (Eastman Kodak, Rochester, NY, USA) at a range of
temperatures. Performance was evaluated with respect to base plug fog density,
relative speed and contrast. RESULTS: All solutions produced acceptable base plus
fog values. MGS produced significantly greater densities (P < 0.05) than the
other three solutions. Contrast obtained with Kodak and Fuji solutions was less
than with MGS and HAC. Developing temperature recommended by the manufacturer of
the processor were found to be higher than that needed to achieve a clinically
acceptable film. CONCLUSIONS: Depending on the processor and processing solutions
used, exposure time and processing temperature can be modified while maintaining
image quality. The cheapest processing solution (MGS) gave the same results as
the more expensive.
PMID- 9656876
TI - Comparison of arthroscopy and radiography in patients with temporomandibular
joint symptoms and generalized arthritis.
AB - OBJECTIVE: To compare arthroscopy with radiography in patients with
temporomandibular joint (TMJ) symptoms and generalized joint disease. METHODS:
Twenty patients with generalized osteoarthritis (GOA) and TMJ symptoms and 21
patients with rheumatoid arthritis (RA) and TMJ symptoms were examined with
arthroscopy and radiography (individualized oblique lateral transcranial
projections and sagittal and frontal tomography). RESULTS: In the GOA group there
was a significant correlation between pronounced degenerative changes at
arthroscopy and flattening of the eminence and reduced joint space superiorly and
posteriorly on radiographs and between moderate to pronounced bone or disk
remodelling and reduced joint space superiorly and posteriorly. In the RA group
there was a significant correlation between moderate to pronounced degenerative
changes at arthroscopy and radiographically extensive erosions in the condyle and
between moderate to pronounced fibrosis and reduced translation. CONCLUSION:
Compared with conventional tomography, arthroscopy revealed TMJ pathology earlier
and more frequently. It may therefore in individual cases be the first choice
examination, particularly as treatment can be given simultaneously.
PMID- 9656877
TI - Chondrosarcoma of the maxilla: panoramic radiographic and computed tomographic
with multiplanar reconstruction findings.
AB - Chondrosarcomas are extremely rare tumors of which approximately 10% are found in
the maxillofacial region. In this report, we present the imaging findings of a
maxillary chondrosarcoma on a panoramic radiograph of the jaws and computed
tomography with multiplanar reconstructions. We recommend the latter as an
excellent way to image evolving or suspected lesions of the maxilla, particularly
for surgical treatment planning.
PMID- 9656878
TI - Aesthetics for the next millennium.
AB - The approach of a new millenium provides us, as rhinoplasty surgeons, the
opportunity to reflect on where we are and where we are going. Aesthetically,
there are several trends that are evident today. The first is the desire for a
natural, unoperated appearance to the final rhinoplasty result. Second, is that
our patient population continues to be more racially diverse; Caucasian normative
standards of facial analysis are no longer sufficient. What is required is a
broader understanding of ethnically specific facial features. Third, the standard
values of facial and nasal analysis are derived from population means. If we
desire to create beauty, these standards may not be adequate. Beauty is an ill
defined concept that is obvious to the observer and recognized cross-culturally,
however, it is difficult to quantify. To consistently achieve beautiful
rhinoplasty results, we must start with an understanding of what our aesthetic
ideals should be. This has yet to be satisfactorily defined for all racial groups
and remains a challenge for the future.
PMID- 9656879
TI - Anatomy of a rhinoplasty: emphasis on the middle third of the nose.
AB - The nose is an organ that serves many functions. These functions are intimately
involved in an organ that occupies a very aesthetically prominent position on the
face. A thorough knowledge of the anatomy is of the utmost importance for
surgeons attempting to preserve or improve the functional capability and the
aesthetic appearance of the nose. Nasal anatomy is extremely complex with a
myriad of different three-dimensional variances. The middle third of the nose has
largely been overlooked in its importance. The components of this portions of the
nose consist of the paired upper lateral cartilages, the dorsal aspect of the
septum, and the scroll of the upper lateral cartilages upon the lower lateral
cartilages. This area is of key importance to the nasal valve area and can have a
major impact on the functional capabilities of the nose. A description of the
confluence of the flare of the septum to the upper lateral cartilages is
necessary for an understanding of changes that may occur during rhinoplastic
operations. A knowledge of the anatomy of the middle third of the nose may
prevent nasal valve collapse, a pinched appearance of this portion of the nose,
or an aesthetically unappealing appearance.
PMID- 9656880
TI - Surgery of the nasal tip.
AB - One of the most challenging aspects of cosmetic rhinoplasty is nasal tip
refinement. In efforts to control tip rotation, projection and architecture,
surgeons face constant tradeoffs between tip position and dorsal reduction. Open
structure rhinoplasty allows direct visualization of bony-cartilaginous
deformities, preservation of nasal structural integrity and precise nasal tip
alteration. The open rhinoplasty technique involves, control of tip projection
and rotation, reshaping of nasal tip cartilage, minimal resection of the nasal
dorsum and lower lateral cartilage and preservation or reinforcement of major tip
supports. The advantage of open structure rhinoplasty includes preservation of
inherent nasal supporting elements and precise nasal reshaping which are
essential for aesthetically pleasing and predictable postoperative results.
PMID- 9656881
TI - Structural grafting in rhinoplasty.
AB - The need for structural grafting in rhinoplasty arises when the nasal skeletal
framework is weakened, malpositioned, or both. This review will be limited to
structural grafting of the cartilaginous nasal skeleton. Current techniques will
be reviewed and a technique introduced that addresses the common deformity of a
superiorly rotated and deprojected nasal tip complex while simultaneously
correcting nasal valve collapse. This technique is referred to as the Dynamic
Adjustable Rotational Tip (DART) technique. The operative technique of the DART,
as well as the basic philosophy regarding the tensile nature of the cartilaginous
nasal skeleton will be described.
PMID- 9656882
TI - Implants in rhinoplasty.
AB - A variety of materials have been employed in rhinoplasty for augmentation and
reconstruction. While autogenous tissue remains the mainstay of nasal implants
and are the clear choice for structural and augmentation grafting of the nasal
tip, limited availability and unpredictable resorption or remodeling have made
homologous and synthetic implants important considerations for dorsal
augmentation grafting. This section discusses categories of graft materials,
their physical properties, harvesting and preparation technique, and advantages
and disadvantages. An algorithm for nasal implants for specific indications in
support and augmentation is presented.
PMID- 9656883
TI - Powered instrumentation for dorsal reduction.
AB - We describe the use of powered instrumentation for precise modification of the
bony nasal dorsum. Specific modifications were made to design a drill
specifically for the bony nasal dorsum. This drill has a protective sheath that
covers all but the active part of the drill, protecting the skin-soft tissue
envelope, and it also has suction at the resection site. In some cases an
osteotome is used to reduce the hump and the drill is used to achieve additional
reduction and to smooth the exposed edges under direct vision. In other cases the
entire bony hump is reduced using the drill. The nasal dorsum drill offers a
precise alternative to the rasp. The precision of the drill is highlighted in
cases in which limited reduction is needed, as in cases of a single or several
spicules requiring reduction and smoothing after osteotomy, or a single 4 mm
raised area requiring limited reduction. The design of rasps makes it difficult
to work on these focal areas without unnecessarily rasping surrounding areas,
whereas the drill may be used to reduce the entire hump, to smooth the edges
after osteotomy, or in a more precise and limited fashion when indicated. The
drill may be less traumatic to the skin-soft tissue envelope because it does not
rely on the potentially bruising back and forth motion typical of rasping. The
nasal dorsum drill may decrease the incidence of bony dorsal irregularities after
rhinoplasty.
PMID- 9656884
TI - Revision rhinoplasty for monographs in facial plastic surgery contemporary
rhinoplasty.
AB - Revision rhinoplasty represents the amalgamation of years of knowledge, judgment,
technique, communication, self-critique, and patient selection. The surgeon's
ego, economics, or personality should not persuade or dissuade him or her from
undertaking revision rhinoplasty. This decision should be made after critical
evaluation of his/her skills at technical execution, and communicating with the
patient, as well as the patient's perception and expectations. If any concern
exists, delay. Re-evaluation and referral become prudent. These patients may
already be angry. They are obviously dissatisfied with their results and have
frequently had attempts at revision by the previous surgeon. All these factors
complicate the psychological aspects of an already difficult task. One other
realization is the fact that this now becomes your result if it is the revision
of a colleague's surgery. When comfortable with all of these factors, revision
rhinoplasty can then be undertaken. The need for revision may be subtle or
grotesque and can result from a multitude of factors: unrecognized deformities at
the primary surgery; misunderstood consequences of technique; poor technique;
unfavorable healing; postsurgical injury; the inevitable need for revision
surgery in a difficult nose; and poor aesthetic judgment. Revision of one's own
results is emotionally more difficult, but functionally and technically easier. A
complete understanding of the primary surgery, access to the initial photographs,
and a rapport with a patient who is willing to return are all helpful in
achieving a satisfactory result. In approaching the correction of postoperative
deformities, it is important to have an understanding of the anatomic abnormality
as well as the aesthetic deformity. Recognizing the anatomic cause of the
postsurgical deformity is more relevant to their avoidance and to the maturation
of the surgeon than to their correction and the desired aesthetic result except
when functional abnormalities exist and need correction. Ultimately it is the
deformity that needs to be corrected, and this may or may not require the
restoration of anatomic normalcy.
PMID- 9656885
TI - Reconstructive rhinoplasty.
AB - Reconstructive rhinoplasty for larger nasal defects requires a three-dimensional
perspective using many of the aesthetic and functional techniques commonly
employed in rhinoplasty. There are numerous ways of addressing a deficiency of
the internal lining and each technique is detailed. Structural grafting is
imperative in order to resist the contracture and collapse of the reconstructive
nose. These grafts are also used to enhance contour and definition. Resurfacing
of large cutaneous defects is frequently achieved through the midline forehead
flap. There are many subtle maneuvers which can significantly impact the final
aesthetic outcome and these are discussed below. This article highlights the
three-layered approach to subtotal and total reconstructive rhinoplasty.
PMID- 9656886
TI - Photo documentation in rhinoplasty.
AB - Taking good clinical photographs can be simple and fast if a few basic principles
are followed. An overview of basic photography with an emphasis on germane
principles is followed by brief discussions of equipment, lighting, positioning,
and common mistakes. The simplest way to take good photographs is presented. More
advanced techniques are also discussed. Finally, attention to details in
examining pre- and postoperative photographs is stressed.
PMID- 9656887
TI - Substance P-associated increase of intra-articular temperature and pain threshold
in the arthritic TMJ.
AB - Neuropeptides are considered mediators and modulators of inflammatory joint
disease. Substance P (SP) has been proposed as a mediator of pain, and its
vasoactive properties are well documented. In this study, the presence of SP-like
immunoreactivity in the synovial fluid was correlated to intra-articular
temperature (IAT) and pain from the arthritic temporomandibular joint (TMJ) 3 to
5 weeks after one intra-articular injection of glucocorticosteroids. Eighteen
TMJs were investigated for IAT and the presence of SP-like immunoreactivity in
the synovial fluid in 12 patients with systemic inflammatory joint disease. After
arthrocentesis, the aspirates were analyzed for SP-like immunoreactivity by means
of competitive radio immunoassay. A visual analogue scale and an algometer
determining the pressure pain threshold and tolerance level assessed arthritic
pain and hyperalgesia in the TMJ. Our results indicate that SP-like
immunoreactivity is associated with IAT and that increased concentrations of
joint fluid SP-like immunoreactivity correspond to increased pain threshold and
tolerance and a concomitantly decreased visual analogue scale. These findings
suggest that SP is implicated in the vascular and nociceptive response of the
arthritic joint and that SP, possibly assisted by the antinociceptive effect of
local corticosteroids, has a modulatory role in arthritic pain and hyperalgesia.
PMID- 9656888
TI - Capsaicin application to the temporomandibular joint alters calcitonin gene
related peptide levels in the trigeminal ganglion of the rat.
AB - The aim of this investigation was to determine the temporal effect of an intra
articular injection of capsaicin to the temporomandibular joint on the levels of
calcitonin gene-related peptide-like immunoreactivity (CGRP-ir) in the trigeminal
ganglion of the rat. The temporomandibular joints of 26 adult female rats were
injected on one side with capsaicin and contralaterally with a control vehicle.
Another 8 animals served as an untreated control group and received no
injections. Animals were sacrificed at time intervals of 4 hours, 48 hours, 10
days, and 21 days following treatment. The trigeminal ganglia were extirpated,
and CGRP-ir levels were quantified using a radioimmunoassay. Results demonstrated
that when the capsaicin-treated side and the vehicle-treated side were compared,
CGRP-ir levels decreased initially at 4 hours and increased at 48 hours. At 10
days, CGRP-ir levels had again dropped below control levels, followed by an
increase at 21 days. CGRP-ir levels for the first two time periods investigated,
which simulate an acute inflammatory state, mimic results observed in studies
using limb joints, while the other time periods, which represent an intermediate
and a chronic condition, respectively, suggest a more complex interaction with
capsaicin-sensitive primary afferents.
PMID- 9656889
TI - Triazolam improves sleep but fails to alter pain in TMD patients.
AB - Patients with chronic orofacial pain often report disturbances in sleep, leading
to the hypothesis that nocturnal motor hyperactivity of the muscles of
mastication may contribute to the nociceptive process. This hypothesis was tested
in a controlled study to evaluate the relationship between sleep stages, patient
self-report of pain in the orofacial region, and nocturnal masticatory muscle
activity. Twenty subjects participating in a two-period, within-subject,
crossover study received triazolam or placebo for 4 nights. Sleep, pain, and
mandibular range of motion were assessed at baseline, following the first period,
and again following the second period; a 3-day washout period separated the two
treatments. Subjective report of sleep quality was significantly improved
following triazolam in comparison to placebo as measured by category scales for
sleep quality, restfulness, and sleep compared to usual. The amount of time spent
in stage-2 sleep was also significantly increased by triazolam. No improvement
was seen in pain as measured by palpation with an algometer, in scales for
sensory intensity and the affective component of pain, or in daily pain diaries.
Mean facial muscle electromyographic activity for 30-second epochs averaged over
the entire period of sleep did not reveal any differences in muscle activity
across the three conditions. These data indicate that improvements in sleep
quality and alterations in sleep architecture do not affect nocturnal facial
muscle activity or subsequent pain report in temporomandibular patients, thereby
failing to support the hypothesized relationship between sleep disturbances and
chronic orofacial pain.
PMID- 9656890
TI - Physical therapy for patients with TMD: a descriptive study of treatment,
disability, and health status.
AB - The purposes of this study were to compare disabilities and health status
associated with temporomandibular disorders (TMD) to other musculoskeletal
disorders, to describe the types of physical therapy administered to patients
with TMD, and to evaluate health-related quality of life (HRQOL) as an index of
clinical change following physical therapy treatment. Outcomes for 56 patients
(mean age 40 years, SD 13 years; 89% female) were evaluated from a large database
generated by the Focus on Therapeutic Outcomes network. A generic assessment of
HRQOL--the Medical Outcomes Study (MOS) 17--was used to evaluate the physical and
mental aspects of disability associated with TMD, and the results were compared
descriptively to three groups of patients with different cervical pain syndromes.
The results showed that patients with TMD had limitations in social function,
emotional well-being, and energy level similar to patients with cervical
disorders. Physical function (i.e., walking, carrying loads, or lifting),
however, was much more limited in cervical disorder patients and bodily pain
interfered more with daily work. Large positive effect sizes (> 0.80) in the
areas of social function and bodily pain indicated clinical improvement for
patients with TMD at the completion of physical therapy. The results suggest that
the MOS-17 may be useful as one measure of clinical change for patients with TMD
who receive physical therapy.
PMID- 9656891
TI - Somatic complaints, psychologic distress, and treatment outcome in two groups of
TMD patients, one previously subjected to whiplash injury.
AB - The aim of this study was to compare somatic complaints and psychologic distress
in a group of whiplash patients with temporomandibular disorders (TMD) and a
group of patients with TMD only, and to assess the outcome after conservative TMD
treatment consisting of counseling, muscle exercises, and a stabilization splint.
Each group consisted of 16 patients (12 women and 4 men) with a mean age of 42
years. The duration of the symptoms was from 1 to 3 years. In addition to a
functional clinical examination and a recording of headache frequency and
intensity, the patients answered three questionnaires: a Somatic Complaints
Questionnaire (SCQ); the trait portion of Spielberger's State-Trait Anxiety
Inventory; and the Symptom Checklist-90-Revised (SCL-90-R). The whiplash patients
had higher scores than the TMD patients on the SCQ muscle score and on the
following subscores of SCL-90-R: obsession, somatization, depression, and
anger/hostility. The treatment outcome as assessed by the change of self-reported
frequency of headache, number of tender muscles upon palpation, and change of
values on a visual analogue scale for headache intensity showed that the whiplash
patients obtained only a decrease in the proportion of tender muscles, while
those in the TMD only group showed improvement on all treatment criteria.
PMID- 9656892
TI - Effect of parafunctional clenching on TMD pain.
AB - Parafunctional activities are assumed to play an important role in
temporomandibular disorders (TMD), but experimental data in support of this
hypothesis are lacking. This study examined the role of parafunctional clenching
on various measures of TMD pain. Five subjects participated in daily 17-minute
electromyogram biofeedback training sessions structured in three phases. Subjects
were instructed to maintain temporalis and masseter muscle activity below 2
microV in the first (decrease) phase of training (10 sessions), above 10 microV
in the second (increase) phase (1 to 8 sessions), and below 2 microV in the third
(decrease) phase (10 to 15 sessions). Preliminary screening examinations showed
that none of the subjects had TMD. Two subjects reported intolerable pain during
increase training, and both were diagnosed with a TMD during this phase. No
subject was diagnosed with TMD pain during either decrease training phase. The
authors conclude that chronic, low-level parafunctional clenching may be a factor
in the cause of TMD pain.
PMID- 9656893
TI - Evaluation of shear stress of the human temporomandibular joint disc.
AB - The aim of this study was to determine the shear stress of the human postmortem
temporomandibular joint (TMJ) disc. Correlation of shear stress with age or with
the region of the disc was determined. Nine discs were removed unilaterally from
postmortem humans, ages 36 to 76 years. Discs were sectioned into lateral
(eight), central (eight), and medial (eight) specimens. Each specimen was
attached by cyanoacrylate adhesive to a servohydraulic test system apparatus
within 48 hours of retrieval. Shear properties were measured under quasistatic
conditions with a linear increase of displacement until the specimen failed to
maintain maximum resistance to the applied force. The shear moduli were analyzed
by means of the Wilcoxon's signed ranks test. The results showed that values of
shear moduli on peripheral portions (lateral and medial) were significantly
higher than on central portions (P = 0.0013). The correlation between the shear
moduli of TMJ discs and age showed a regression slope for shear moduli of -0.326
+ 0.031 x age (r = 0.769; P < 0.01). Peripheral portions (lateral and medial)
have a higher shear moduli and are stiffer than the central portions of discs and
shear moduli or stiffness of TMJ discs increase with age.
PMID- 9656894
TI - Muscle pain modulates mastication: an experimental study in humans.
AB - In this study, pain was induced in the masseter muscle by tonic infusion of
hypertonic saline (5%) for up to 800 seconds in 12 healthy men. Subjects
continuously scored the pain intensity on a 10-cm visual analogue scale.
Mastication ipsilateral and contralateral to the infusion side was quantitatively
assessed with the use of jaw-tracking and electromyograph recordings of jaw
closing muscles before, during, and after periods of constant muscle pain
intensity. The maximum voluntary occlusal force (MVOF) during short static
contractions also was monitored. Jaw movements and electromyographic data were
divided into single masticatory cycles and analyzed on a cycle-by-cycle basis to
account for intercycle variability. In all subjects, tonic infusion caused a deep
localized pain at a clinically relevant intensity (mean VAS +/- SE, 4.6 +/- .3
cm). MVOF was significantly affected by muscle pain (P < .0005), with
significantly lower MVOF during pain compared to prepain and postpain (P < .05).
In a significant number of masticatory cycles, the averaged electromyograph
activity of all jaw-closing muscles during their agonist function was decreased
for both ipsilateral and contralateral painful mastication (P < .05). These
electromyographic changes are probably a reflection of the natural bilateral
recruitment pattern of jaw-closing muscles during mastication. Significant
changes in jaw movements during painful mastication could not be detected with
the present jaw-tracking device, but further studies with more accurate and
sensitive devices are needed.
PMID- 9656895
TI - The reproducibility of muscle and joint tenderness detection methods and maximum
mandibular movement measurement for the temporomandibular system.
AB - The purpose of this study was (1) to evaluate the reproducibility of two
masticatory muscle and joint tenderness detection methods; (2) to evaluate the
reproducibility of maximum mandibular movement measurements; and (3) to
investigate factors influencing examiner agreement. The tenderness assessment
procedures involved application of a standard pressure for 2 seconds over four
anatomically defined masticatory muscle sites, one control forehead site, and two
temporomandibular joint sites on each side of the face. One technique utilized a
pressure algometer (PAP), while the other technique required that a trained
examiner apply pressure with the index fingertip (FPP). Seventy-two subjects (36
patients and 36 controls) were evaluated in a single-blind study design. Control
subjects were matched for age, gender, and race with temporomandibular disorder
subjects. Each subject was examined twice with each of the described methods in a
randomized, fully balanced sequence by calibrated examiners. Tenderness levels
were determined by the subject via self-report of pain upon pressure using a
standard set of verbal descriptors. Maximum pain-free, active, and passive
opening, and maximum active right and left lateral movements were measured using
a millimeter ruler. Intraclass correlation coefficients (ICC) for the tenderness
assessment methods ranged from 0.220 to 0.739 for the FPP method and from 0.391
to 0.880 for the PAP method. ICCs for mandibular movement measurement were much
less variable, ranging from 0.59 to 0.68 for lateral movement and from 0.78 to
0.93 for opening movement. These results indicate good to excellent agreement
between calibrated examiners for mandibular movement measurement and for
tenderness assessment methods at two masseter (i.e., superficial and deep) and
the anterior temporalis sites. Only fair agreement was found for the middle
temporalis and lateral TMJ capsule sites using these methods.
PMID- 9656896
TI - Pain threshold responses to two different modes of sensory stimulation in
patients with orofacial muscular pain: psychologic considerations.
AB - This study focuses on the influence of trait anxiety and mood variables on
changes in tooth pain threshold following two similar methods of somatic afferent
stimulation, one familiar (manual acupuncture) and one unfamiliar (low-frequency
transcutaneous electrical nerve stimulation [low-TENS]). Twenty-one acupuncture
responders, treated for long-lasting orofacial muscular pain but naive to low
TENS, were selected for the study. In an experimental session, acupuncture and
low-TENS were randomly given during two periods separated by a rest interval.
Tooth pain thresholds (PT) were measured before and after stimulation with a
computerized electrical pulp tester. Trait anxiety and depression were assessed
with psychometric forms before the experimental session in all patients, whereas
momentary mood was assessed in 10 randomly selected patients with visual analogue
scales during and after the two types of stimulation. Following acupuncture, the
group average PT increased significantly, whereas no significant change was
observed following low-TENS. Higher scores on trait anxiety correlated
significantly with a low PT increase following low-TENS, and higher ratings of
stress correlated significantly with a low PT increase following acupuncture.
This indicates that the magnitude of analgesia induced by these methods may be
modified by psychologic factors like anxiety and stress.
PMID- 9656897
TI - Comparison of clinical and psychologic features of fibromyalgia and masticatory
myofascial pain.
AB - The aim of this study was to investigate common symptoms and divergent features
in fibromyalgia (FS) and masticatory myofascial pain (MFP) in patients affected
by craniomandibular disorders. Twenty-three women with MFP and 23 women with FS
were studied. All patients were examined by a dentist and by a rheumatologist.
Craniomandibular disorders were assessed with a subjective symptoms
questionnaire, detailed history interview, joint function examination, and manual
palpation of masticatory and cervical muscles. The Middlesex Hospital
Questionnaire was used to obtain personality profiles of the patients. The
craniomandibular disorders questionnaire revealed various similarities in the two
groups, the most striking of which were pain during mandibular function,
articular noises, and headache. Both groups had muscle pain upon palpation; the
mean scores (on a 0 to 4 scale) did not differ significantly between the two
groups and ranged between 1.39 (SD 1.2) and 2.86 (SD 0.75). The mean value of
active mouth opening was 40.9 mm (SD 9.1) in MFP patients and 44.6 mm (SD 7.2) in
FS patients, while the mean value of passive opening was 49.6 mm (SD 6.0) in MFP
patients and 49.8 mm (SD 3.5) in FS patients. These values did not differ
significantly between the two groups, but did differ from the normal population,
similar to the trend of the psychologic profile. The authors conclude that the
physician should be alert to the need to conduct interdisciplinary evaluations in
the diagnosis and management of FS and of MFP.
PMID- 9656898
TI - Temporomandibular disorders in children and adolescents: reliability of a
questionnaire, clinical examination, and diagnosis.
AB - Recently developed Research Diagnostic Criteria for Temporomandibular Disorders
(RDC/TMD) have been shown to be reliable for diagnosing and assessing TMD in U.S.
and Swedish adult populations; however, few studies have focused on clinical
examination methods and diagnostic criteria for use with children and
adolescents. The present study used a sample of 50 Swedish children and
adolescents, aged 12 to 18 years, to evaluate usefulness and reliability of
existing and specially developed measures and methods for assessing and
diagnosing TMD in youth. Subjects underwent repeated clinical exams by two
calibrated examiners to assess signs and symptoms per the RDC/TMD, and they
responded to a specially developed self-administered questionnaire that addressed
location and frequency of TMD-related pain and symptoms, jaw function, effect of
pain on daily activities, and use of pain medications. Interexaminer and
intraexaminer reliability was assessed for clinical examination, questionnaire
items, and diagnosis. Reliability values ranged from acceptable to excellent for
the RDC/TMD clinical exam and questionnaire, and from good to excellent
reliability for measuring virtually all modified clinical parameters of TMD
assessed in these young patients.
PMID- 9656899
TI - Pain preceding recurrent head and neck cancer.
AB - Over a 7-year period, 12 patients experienced recurrence of primary head and neck
cancers preceded by severe orofacial pain. Pain began within 6 months following
treatment in 10 of 12 patients and was progressive in 11 of 12 patients. Six
patients died from recurrence, five within 2 years following onset of pain. No
clear indication of malignant disease was evident despite clinical examination,
plain radiography, magnetic resonance imaging, and computed tomography. Pain was
often mistaken for denture irritation. Frequently, no area of irritation was
apparent.
PMID- 9656900
TI - Treatment-seeking patterns of facial pain patients: many possibilities, limited
satisfaction.
AB - Knowledge about the different kinds of treatment provided to patients with
nonmalignant musculoskeletal facial pain is limited. The present study was based
on 206 consecutive patients who were referred to a university-based tertiary care
clinic for the diagnosis and management of persistent facial pain. Its purpose
was to get information about the number and specialty of providers consulted by
patients prior to their referral, and to follow the underlying treatment-seeking
patterns. The results showed that on average 4.88 providers from 44 different
categories were consulted. A general dentist or a dental specialist was seen by
about 70% of patients. For patients whose first provider was a dentist, the most
likely subsequent provider was another dentist. Conversely, if the first provider
was a physician, chances were greater that the subsequent provider was a
physician rather than a dentist. Among the nondental therapies patients received,
physical therapy was chosen most frequently (42.2%). More than 60% of patients
had at least one nondental treatment; however, the majority of these patients
experienced two or more different types of such therapy (e.g., chiropractic,
osteopathic, relaxation training). Patients' satisfaction with care and treatment
was moderate, since only 18.5% of the patients were very satisfied, while 27.7%
were dissatisfied or very dissatisfied. The present findings, which corroborate a
recent study from the Kansas City, Missouri, region, indicate that patients with
persistent facial pain see a large number of different providers, and that
nonmedical/nondental treatment approaches are common. The moderate satisfaction
experienced with any of the therapies points out that much needs to be done
before this patient population is served satisfactorily.
PMID- 9656901
TI - TMD treatment need in relation to age, gender, stress, and diagnostic subgroup.
AB - Associations between treatment need for temporomandibular disorders (TMD) and
age, gender, stress, and diagnostic subgroup were analyzed in an adult Finnish
population sample of 506 subjects. When analyzed separately, the association
between TMD treatment need and all the studied factors was statistically
significant. This finding is in accordance with earlier results. When the studied
factors were included into an explanatory model, however, the picture changed.
The logistic regression analysis revealed that diagnostic subgroup was the
strongest predictor for the TMD treatment need. Total stress score significantly
added to the explanatory power of the model, but age and gender did not. The
commonplace observation that women show more signs and symptoms of TMD seems to
be explainable by their higher stress scores and by the type of symptoms.
PMID- 9656902
TI - The long-term effect of occlusal therapy on self-administered treatment outcomes
of TMD.
AB - Because of a lack of substantial scientific data, the efficacy of occlusal
therapy for the management of temporomandibular disorders (TMD) is still
controversial. Of a total of 1405 consecutive TMD patients examined over the last
10 years, 369 (26.3%) were determined to have completed treatment at least 1 year
before the present survey. A sample questionnaire was mailed to each patient in
this sample population. The questionnaire failed to reach 46 patients; of the 323
patients who received the questionnaire, 260 (80.5%) responded. The mean duration
of time between their last visit and this survey was 3.7 years. The questionnaire
elicited information on treatment outcomes, present treatment needs, and current
signs and symptoms. Participants were divided into two treatment groups: (a)
those who underwent some occlusal therapies (Phase II) following successful
reversible therapies (Phase I) (20 men and 114 women); and (b) those who
underwent reversible therapy only (33 men and 93 women). Participants were
further differentially diagnosed into five diagnostic subgroups of TMD, based on
the clinical examination at the initial visit, tomography, and, for some
patients, magnetic resonance imaging. The subgroups included myalgia, arthralgia,
anterior disc displacement with an without reduction, and
osteoarthritis/osteoarthrosis. Only 12.3% of the total population surveyed
reported lack of improvement to an acceptable level and further need for
treatment. The remaining patients reported satisfactory results in the reduction
of TMD symptomatology and no further need for treatment, because their symptoms
had either disappeared or improved to an acceptable level. Regardless of
treatment groups and diagnostic subgroups, the current subjective signs and
symptoms were negligible in most patients, and mean mouth openings were in the
normal range. No particular diagnostic subgroups seemed to have significantly
better outcome following Phase II occlusal therapy. These results suggest that
the majority of TMD signs and symptoms improve to an acceptable level with only
reversible therapy, and the long-term value of additional occlusal therapy
following reversible therapy is minimal. Therefore, permanent occlusion-changing
therapies apparently are not generally needed to maintain TMD symptom reduction
over time.
PMID- 9656903
TI - Pain descriptors characteristic of persistent facial pain.
AB - The McGill Pain Questionnaire is an instrument that is widely used to assess the
multidimensional experience of pain. Although it was introduced more than 20
years ago, limited information is available about its use in patients suffering
from persistent facial pain. The aim of this study was to investigate the
response patterns of persistent facial pain patients to the McGill Pain
Questionnaire, to correlate these patterns with patients' beliefs about the
seriousness of the condition, and to compare the findings with data reported from
other painful conditions. The study sample consisted of 200 consecutive female
patients referred to a tertiary care facial pain clinic. The Pain Rating Index
scores of the McGill Pain Questionnaire subscales and the total number of words
chosen by these patients closely matched the summary scores reported by Wilkie et
al, who pooled data from seven pain conditions (cancer, chronic back, mixed
chronic, acute/postoperative, labor/gynecological, dental, and experimentally
induced) in their meta-analysis. On the other hand, when the data collected in
this study were compared with those from specific clinical subsets, such as
cancer patients, chronic back pain patients, or dental patients, differences in
McGill Pain Questionnaire scores could be identified. Differences were also found
in the choice of specific pain descriptors. More than 20% of the facial pain
patients selected "radiating" and "pressing"; this was not the case for those
suffering from other pain conditions. Facial pain patients who felt that their
condition was more serious or different from what the treatment providers had
told them had a greater likelihood of choosing specific word categories of the
McGill Pain Questionnaire.
PMID- 9656904
TI - The effects of tongue position on mandibular muscle activity.
AB - The purpose of this study was to determine the relationship between tongue
position and mandibular muscle activity. Thirty-three subjects (28 women) between
the ages of 18 and 34 years (mean = 22.1 years) with no prior injury to or pain
in the jaw, mouth, or tongue participated in the study. Subjects were asked to
rest quietly while baseline electromyographic recordings were made from the
temporalis, masseter, and suprahyoid muscle regions. Afterwards, subjects were
randomly assigned to conditions requiring them to position the tongue either
"against the anterior palate" or "on the floor of the mouth, making sure the tip
does not press against any part of the mouth." The results indicated that right
temporalis activity was higher when the tongue was positioned against the roof of
the mouth than when it was either at baseline or resting on the floor of the
mouth (P < .03). A similar pattern of results was observed for the suprahyoid
muscle group (P < .01). There were no significant differences in masseter muscle
activity as a function of tongue position (Ps > .20). These findings suggest
caution in labeling the "rest" position of the tongue and indicate that further
study of the relationship between tongue position and orofacial pains in needed.
PMID- 9656905
TI - Waking and sleeping temporalis EMG levels in tension-type headache patients.
AB - Temporalis muscle activity in tension-type headache subjects (n = 36) and in
matched nonheadache controls (n = 36) was evaluated in this study. Subjects'
cumulative temporalis muscle activity was recorded every 30 minutes for 3 days
and night using an electromyographic recorder. Analysis of variance showed that
neither the waking nor the sleeping overall muscle activity levels for these two
groups were statistically different. When the waking EMG data were dichotomized
into function and nonfunction activities, a significant difference was found
between groups during jaw function (i.e., chewing and talking). These data
suggest that headache subjects are using their temporalis muscles with less
efficiency than nonheadache subjects during function. This elevated EMG is more
likely a consequence of pain (via protective splinting or guarding) rather than a
cause in tension-type headache sufferers.
PMID- 9656906
TI - The efficacy of dry needling and procaine in the treatment of myofascial pain in
the jaw muscles.
AB - In patients with myofascial pain, painful trigger points are often treated using
dry needling and local anesthetic injections. However, the therapeutic effect of
these treatments has been poorly quantified, and the mechanism underlying the
effect is poorly understood. In a randomized, double-blind, double-placebo
clinical trial, a pressure algometer was used to measure pain-pressure thresholds
in the masseter and temporalis muscles of 30 subjects aged 23 to 53 years with
myofascial pain in the jaws, before and after a series of dry needling
treatments, local anesthetic injections, and simulated dry needling and local
anesthetic treatments (treatment group A: Procaine + simulated dry needling;
treatment group B: dry needling + simulated local anesthetic; control group C:
simulated local anesthetic + simulated dry needling). Subjects rated pain
intensity and unpleasantness using visual analogue scales, and the data were
analyzed using analysis of variance. Pain pressure thresholds increased slightly
after treatment, irrespective of the treatment modality. Pain intensity and
unpleasantness scores decreased significantly at the end of treatment in all
groups. There were no statistically significant between-group differences in pain
pressure thresholds and visual analogue scale scores at the end of treatment. The
findings suggest that the general improvement in pain symptoms was the result of
nonspecific, placebo-related factors rather than a true treatment effect. Thus,
the therapeutic value of dry needling and Procaine in the management of
myofascial pain in the jaw muscles is questionable.
PMID- 9656907
TI - The natural course of nonreducing disc displacement of the TMJ: relationship of
clinical findings at initial visit to outcome after 12 months without treatment.
AB - The natural course of untreated nonreducing disc displacement of the
temporomandibular joint was evaluated in 52 patients (total of 57 affected
temporomandibular joints). The association between the clinical findings at the
initial visit and the outcome at 12 months for the age, range of motion for
maximum mouth opening, intercuspal-occlusal relationship, morphology of the
mandibular fossa and the articular eminence, and the locking duration was
evaluated. Good resolution was seen in 59.6% of the patients. The patients with
good resolution were significantly younger than those with poor resolution (P <
.05, two-tailed t test); however, there were no differences in any other factors
between the patients with good resolution and those with poor resolution. Natural
resolution of clinical signs and symptoms was suggested for the majority of
patients with nonreducing disc displacement of the TMJ, and a younger age at the
initial visit appears to be a positive factor in the prognosis.
PMID- 9656908
TI - Adolescent TMJ tomography and magnetic resonance imaging: a comparative analysis.
AB - The predictive value of radiographic tomography was assessed using magnetic
resonance imaging as a definitive test of TMJ soft-tissue status in a
predominantly asymptomatic adolescent sample. Eighty-two TMJs in 41 subjects
(mean age = 12.5 years, range = 10 to 17 years) were independently evaluated
using axially corrected tomography and magnetic resonance imaging. Tests of
comparison and correlation were performed. Correspondence of tomographic
classification to magnetic resonance imaging classification of nondisplacement
(55%), reducing internal derangement (35%), or nonreducing internal derangement
(10%) showed a significant relationship (P < .05). Tomography as a diagnostic
test of abnormal disc position had a sensitivity of 0.43, a specificity of 0.80,
a positive predictive value of 0.64, and a negative predictive value of 0.63.
Tomography is inappropriate as a diagnostic test for TMJ internal derangement.
PMID- 9656909
TI - Bilateral condylar movement patterns in adult subjects.
AB - The purpose of this study was to determine if there was a difference between the
temporomandibular condylar movement patterns of a symptomatic adult population
and those of an asymptomatic adult population. Thirty-five volunteers who were
not seeking treatment for TMD underwent two different assessments for TMD signs
and symptoms: (1) a self-administered questionnaire and (2) a clinical
examination. Based on the information obtained from the questionnaires, subjects
were divided into "reported-symptomatic" and "reported-asymptomatic" groups.
Based on the investigator's clinically evaluation of the same subjects, subjects
were divided into "clinically symptomatic" and "clinically asymptomatic" groups.
To compare condylar movement patterns, both groups of subjects then had their
mandibular border condylar movements measured bilaterally using a sagittal
recording device during maximum opening, maximum protrusion, and maximum left and
right excursion movements. The patterns were separated into two broad groups,
"symmetric" and "asymmetric." Symmetric gliding movements were defined as
uninterrupted bilaterally mirror-like patterns of each condyle with a difference
between left and right total length excursion not exceeding 2 mm during opening
in the sagittal plane or horizontal plane. Our results show that 63% of the
subjects who reported clinically asymptomatic for TMD demonstrated asymmetric
condylar movements. However, 100% of the patients (n = 5) who reported clinically
symptomatic for TMD exhibited asymmetric condylar movements. This finding
suggests that, while a very high percentage of TMD subjects will have asymmetric
condylar movements, condylar movements alone are not necessarily diagnostic of
TMD, and the sagittal recording device may alert the clinician to abnormal
movements.
PMID- 9656910
TI - A comparison of TMD patients with or without prior motor vehicle accident
involvement: treatment and outcomes.
AB - The influence of previous trauma in the management of patients with
temporomandibular disorders (TMD) is controversial. The objectives of this study
were to compare treatment regimens and outcomes in motor vehicle accident trauma
related versus nontrauma-related TMD patients. Files of 50 trauma and 50 matched
nontrauma TMD patients were reviewed. Information concerning treatment received,
progress of symptoms with treatment, and findings from the final examination were
recorded. As a whole group, posttraumatic TMD patients tended to receive more
types of treatment (P < .0001), have more medications prescribed (including
analgesics, P < .001; nonsteroidal anti-inflammatory drugs, P = .001; muscle
relaxants, P = .001; and tricyclic antidepressants, P < .001), have more oral
medicine clinic visits (P = .07) over a longer period of time (P = .06), and have
a poorer treatment outcome (P < .001) as compared to the nontrauma group. When
the patients were separated into TMD diagnostic classification subsets, only some
of these differences between trauma and nontrauma patients were seen, but the
subset group sizes were small and only a few of the groups could be compared.
There did not seem to be a significant effect from settling insurance claims
prior to the last clinic visit. Trauma may be an important prognostic factor in
the management of some TMD patients.
PMID- 9656911
TI - Topical clonidine for orofacial pain: a pilot study.
AB - An open-label trial of clonidine, an alpha 2-adrenergic agonist, was prescribed
for patients with a clinical diagnosis of oral neuropathic pain or neuralgia
involving the oral cavity. Clonidine (0.2 mg/g) was prepared in a cream base and
applied four times daily to the site of pain. Seventeen patients were assessed:
10 were diagnosed with neuropathic pain, and 7 with neuralgia. Two of the 17
patients had complaints overlapping both neuropathic and neuralgic pain. In the
patients with neuropathic pain, an overall mean reduction in severity of burning
of 36% (on a 10-point visual analogue scale) was reported. Half of these patients
reported clinical improvement; however, no patients reported complete resolution
of symptoms. Of the patients with characteristics of neuralgia, 57% improved; and
in those who reported improvement, a mean reduction of approximately 54% was
reported. In the 4 patients with neuralgia who responded, a 94% reduction in pain
was reported, with complete resolution of pain in 2 patients. This open-label
clinical trial suggests that topical clonidine may be effective in the management
of some patients with oral neuralgia-like pain, but may have a more limited
effect in those patients with oral neuropathic pain. Besides type of pain, no
other variables predicted which of the patients would achieve pain reduction with
topical clonidine. Although confirmation of clinical efficacy requires double
blind clinical studies, this initial trial suggests that further study is
warranted.
PMID- 9656912
TI - Effect of systemic versus topical nonsteroidal anti-inflammatory drugs on
postexercise jaw-muscle soreness: a placebo-controlled study.
AB - Certain types of jaw-muscle pain may be managed with pharmacologic treatment.
This study evaluated the effect of topical and systemic nonsteroidal anti
inflammatory drugs on acute postexercise jaw-muscle soreness. Ten men without
temporomandibular disorders performed six 5-minute bouts of submaximal eccentric
jaw exercise. The outcome variables were pressure pain thresholds and pain
tolerance thresholds at the masseter muscles, and maximum voluntary occlusal
force. Surface electromyography from the masseter muscles was used to assess the
development of muscle fatigue during the exercise period. Three treatment
modalities were tested in a placebo-controlled, double-blind approach: (A)
placebo gel and placebo tablets; (B) nonsteroidal anti-inflammatory drug gel (2
g, 5% ibuprofen) and placebo tablets; and (C) placebo gel and nonsteroidal anti
inflammatory drug tablets (400 mg ibuprofen). The subjects used their medication
3 times a day for 3 days in the postexercise period. In the exercise period, the
mean power frequency of the electromyography signal, pressure pain threshold,
pain tolerance threshold, and maximum voluntary occlusal force decreased
significantly (analysis of variance, P < .01). In the postexercise period, the
effect of treatment on pressure pain thresholds was significant (F[2,9] = 4.41, P
= .02). On day 3, treatment with topical nonsteroidal anti-inflammatory drugs was
associated with significantly higher pressure pain thresholds as compared to
treatment with systemic nonsteroidal anti-inflammatory drugs (P < .05) and
placebo (P < .05). Treatment effects on pain tolerance thresholds and on maximum
voluntary occlusal force were nonsignificant. The results demonstrated that
repeated eccentric jaw exercise caused muscle fatigue and low levels of
postexercise pain and soreness. Topical nonsteroidal anti-inflammatory drugs seem
to have some advantages over systemic nonsteroidal anti-inflammatory drugs for
management of exercise-induced jaw-muscle pain.
PMID- 9656914
TI - Strategically replenishing your capital assets.
PMID- 9656913
TI - Guarding against the decline of dental practice value.
PMID- 9656915
TI - Advantages and procedures using air abrasion.
PMID- 9656917
TI - A new paradigm for a new age.
PMID- 9656916
TI - Air abrasions and caries detection dyes. The new standard of care.
PMID- 9656918
TI - The Internet: so you want to get connected.
PMID- 9656919
TI - Writing an expert report.
AB - Anna was flustered. It had been three months since her patient had asked for a
report about the accident. Anna had been procrastinating and now her patient was
threatening to report her to the college if it wasn't ready by Monday. As Anna
sat down at the computer, she did not know where to begin. Should she outline the
history of the accident given by her patient or would any discrepancies between
this history and her patient's version cause problems at the hearing? How much
detail should be included about the assessment and the treatment? Anna felt
uncomfortable expressing an opinion about her patient's prognosis, particularly
since she had not assessed the patient in six months. Anna also wondered how much
to charge for the report and whether she could insist upon payment before
releasing the report. How did she ever get herself into this situation?
PMID- 9656920
TI - Early fracture resistance of amalgapin-retained complex amalgam restorations.
AB - Amalgapins are susceptible to early fracture during matrix removal and carving.
The purpose of this study was to examine the early fracture resistance of
amalgapin-retained restorations using a spherical amalgam alloy, an admixed
amalgam alloy, a combination of admixed alloy over the spherical alloy, and a
recently introduced modified spherical amalgam alloy. Four amalgapin channels
with a diameter of 1.4 mm and depth of 2 mm were prepared in cylinders of Macor,
a machinable ceramic material. The amalgapins were hand condensed, and the bulk
of the restoration was mechanically condensed. In the group using the combination
of alloys, 800 mg of spherical alloy was condensed into the amalgapins and over
the floor of the preparation. The admixed alloy was then condensed over the
spherical alloy to build up the bulk of the restoration. Using an Instron
Universal Testing Machine, the restorations were tested to shear failure at an
average of 15.8 +/- 1.3 minutes after the initiation of trituration of the
amalgam alloy. A metal ring was placed around the restoration and pulled 90
degrees to the long axis to simulate matrix band removal. Data were analyzed
using Kruskal-Wallis procedures. The fracture resistance of the spherical alloy
group and the spherical/admixed group were significantly higher than admixed or
Tytin FC. All fractures occurred in amalgam at the entrance to the amalgapin
channel. The combination of spherical and admixed amalgam alloys in a restoration
may reduce the potential for early dislodgment while allowing additional time for
carving.
PMID- 9656921
TI - Effects of lining materials on shear bond strength of amalgam and gallium alloy
restorations.
AB - In this in vitro study, where alloys were condensed into unset paste lining
materials, shear bond strengths were significantly greater than with the unlined
controls. The use of varnish or Paama 2 linings did not significantly increase
the shear bond strength of amalgam or gallium alloy restorations. The use of
Vitrabond, Vitremer, or Resinomer liners significantly increased the shear bond
strength compared to unlined restorations. Permite C restorations lined with
Resinomer all showed cohesive failure within the mixed alloy/ liner. Of the
unlined restorations, Permite C had significantly higher shear bond strength than
Lojic Plus. The experimental method used in the present study proved to be
suitable for quantitative comparison of the shear bond strength of different
dental materials.
PMID- 9656922
TI - Shear bond strength of immediately repaired light-cured composite resin
restorations.
AB - The goal of this study was to examine the extent to which the state of the
surface of newly placed restorations made of one of two commercial formulations
of composite resin (Pertac-Hybrid and Z-100) affects the interfacial bond
strength when such restorations are immediately repaired with the same resin.
Three groups of specimens for each material were prepared: one group in which
there was an air-inhibited film on the surface of the initial layer of the
restoration, another in which that film was prevented from being formed, and a
third in which that surface was abraded prior to placement of the repair layer.
All specimens were stored for 6 weeks in water at 23 degrees C before being
loaded to fracture in shear at a rate of 5 mm/min. The shear bond strength
results were treated using the three-parameter Weibull equation and a clearly
defined index of performance (I), which is a measure of both the magnitude and
variability of the shear bond strength. It was found that, for two states of the
surface of the initial layer, I for Pertac-Hybrid specimens is about the same as
that for Z-100 specimens. For specimens made of either material, there was a
demonstrable difference in I between specimens with or without an air-inhibited
film on the initial layer, while abrading the surface of that layer severely
degraded I.
PMID- 9656923
TI - Using double-poured alginate impressions to fabricate bleaching trays.
AB - Esthetic and diagnostic treatment often requires two casts of one arch, one for
baseline and one for alterations (diagnostic wax-up, bleaching tray, occlusal
analysis). The purpose of this study was to compare the accuracy of stone casts
generated from a second pour of a properly handled alginate impression with first
poured casts. A maxillary dentoform was indexed with six reference spaces (#8-15,
9-2, 2-15, and incisal-to-gingival of #3, 9, 14). Irreversible hydrocolloid
(Jeltrate) impressions were made in perforated steel trays by a single
investigator. Impression material was spatulated for 1 minute. The seated
impression and dentoform were wrapped in a damp paper towel to simulate intraoral
conditions, and allowed to set for 2 minutes. Upon separation, the impression was
stored in a damp towel for 5 minutes. The impression was poured in cast stone
(Microstone) according to the manufacturer's instructions. The stone-filled
impression was immediately rewrapped in a damp paper towel and allowed to set for
45 minutes at room temperature. Upon removal of the stone, the impression was
rinsed with cold water, shaken dry, and repoured in the same manner. Ten
impressions were made: the first five impressions were poured to make casts for
Group A, then repoured as described above for casts for Group B. The remaining
five impressions were poured once to make casts for Group C. The six spaces of
each cast were measured three times in random order using a dial caliper and the
space average calculated for the cast. At each space, analysis of variance showed
no significant difference among Groups A, B, or C (P < 0.05). When alginate
impressions that have been poured with cast stone are kept moist during stone
setting and repoured within 45 minutes, two casts can be generated from one
impression with the same degree of accuracy as two casts made from taking two
separate impressions, providing the alginate does not tear during first cast
removal.
PMID- 9656924
TI - Weight change of various light-cured restorative materials after water immersion.
AB - This study investigated weight changes of various light-cured glass-ionomer
cements and other restorative materials during water immersion and compared
findings with those of conventional glass-ionomer cement and light-cured resin
composites. Three light-cured glass-ionomer cements, two polyacid-modified
composite resins, one conventional glass-ionomer cement, and one light-cured
composite resin were evaluated in this study. The weight changes of these
specimens after water immersion were measured using an electronic analytical
balance and adjusted according to water solubility measured at the same time
weight change was measured. The results were analyzed by one-way ANOVA and
Scheffe's F test at P < 0.05. The weight change of Photac-Fil Aplicap was the
largest, and there were significant differences among the materials (P < 0.05).
Weight change after 6 weeks' water immersion was noted in the following order:
Fuji Ionomer Type II LC, Vitremer, Fuji Ionomer Type II, VariGlass VLC, Geristore
V, and Clearfil AP-X. It is suggested that the amount of water sorption of light
cured glass-ionomer cements is greater than that of polyacid-modified composite
resins.
PMID- 9656925
TI - Temperature and humidity effects on bond strength of a dentinal adhesive.
AB - Dentin specimens from 46 extracted human molar teeth were used in a matched-pair
design examining the factors of temperature/humidity on shear bond strength of a
dentinal adhesive to dentin. For one tooth-half, all procedures using restorative
materials were accomplished in a controlled temperature and humidity chamber
(humidity 95.0 +/- 2.0%, temperature 37.0 +/- 0.3 degrees C). For the other
matched tooth-half all procedures were performed at ambient room conditions
(humidity 52%, temperature 23.3 degrees C/74 degrees F). Oil-free air and water
were used in all restorative procedures. Application of Scotchbond Multi-Purpose
Adhesive System was followed by placement of Z100 Restorative Resin, and
thermocycling 1000 cycles from 5 to 55 degrees C. Each matched specimen was
tested 24 hours later in an Instron Testing Machine. A paired t-test was
performed for comparison of bond strength set values, since they were obtained
from matching halves of the same teeth. Paired t-test comparison showed that the
average humidity/temperature chamber mean of 7.14 +/- 3.12 MPa was significantly
less than the ambient conditions mean of 14.29 +/- 5.07 (P = 0.0000). Bond
strength testing under simulated oral conditions may produce significantly
different findings than customary bench-top laboratory experiments.
PMID- 9656926
TI - Resin-modified glass ionomers: dentin bond strength versus time.
AB - Most dentin bond strength tests of resin-modified glass-ionomer cements have been
conducted after at least 24 hours' storage in water. In a clinical situation,
debonding might occur soon after the restoration was placed if subjected to
stress. The purpose of this study was to investigate the rate of development of
shear bond strength of resin-modified glass-ionomer cements, two Type IIs of
which, Fuji II LC and Vitremer, were used. A conventional glass-ionomer cement,
Fuji II, and a resin composite, Herculite XRV/OptiBond system, were also employed
as controls. Bovine incisors were mounted in self-curing resin, and the facial
surfaces wet ground with 600-grit SiC paper to expose dentin. Materials were
condensed into a vinyl mold and bonded following the manufacturers' instructions.
The shear bond strengths of 10 specimens per group were measured at a crosshead
speed of 1.0 mm/minute after 1, 5, 10, 30, and 60 minutes' and 2, 5, and 24
hours' storage in water at 37 degrees C. One-way ANOVAs followed by the Dunnet
test (P < 0.05) were used to test for significant differences between the mean
bond strength at 1 minute and each of the other test periods. The test period
when there was a significant increase in bond strength was defined as the
"initial increasing time." The dentin bond strengths of all the materials tested
increased with prolonged storage time. The initial increasing times were 10
minutes for Fuji II LC and OptiBond, 20 minutes for Fuji II, and 60 minutes for
Vitremer. The differences in the initial increasing time might have clinical
implications if the restoration is subjected to significant stress immediately
after placement.
PMID- 9656928
TI - How to present a claim for disability insurance.
PMID- 9656929
TI - Speed temporaries, anterior and posterior.
PMID- 9656927
TI - Effect of various infection-control methods for light-cure units on the cure of
composite resins.
AB - This study (1) compared the curing-light intensity with various barrier infection
control methods used to prevent cross contamination, (2) compared the Knoop
hardness value of cured composite resin when various barrier control methods were
used, and (3) correlated the hardness of the composite resin with the light
intensity output when different infection-control methods were used. The light
cure unit tips were covered with barriers, such as cellophane wrap, plastic
gloves, Steri-shields, and finger cots. The control group had no barrier.
Composite resins were then cured for each of the five groups, and their Knoop
hardness values recorded. The results showed that there was significant
statistical difference in the light-intensity output among the five groups.
However, there was no significant statistical difference in the Knoop hardness
values among any of the groups. There was also no correlation between the Knoop
hardness value of the composite resin with the light-intensity output and the
different infection-control methods. Therefore, any of the five infection-control
methods could be used as barriers for preventing cross-contamination of the light
cure unit tip, for the light-intensity output for all five groups exceeded the
recommended value of 300 W/m2. However, to allow a greater margin of error in
clinical situations, the authors recommend that the plastic glove or the
cellophane wrap be used to wrap the light-cure tip, since these barriers allowed
the highest light-intensity output.
PMID- 9656930
TI - New paradigms for anterior tooth preparation. Rationale and technique.
AB - A biologic and esthetic rationale has been presented along with a simplified
controlled technique to achieve predictable results (Figures 13A and 13B). The
clinician is constantly faced with the challenge of developing room for esthetic
material while preserving the biologic objectives. Using the three essential
anterior tooth preparation keys (incisal edge, reduction requirements, and the
biologic zone) enhances predictability. Developing the incisal edge relative to
the dynamics of facial esthetics provides the initial starting point of tooth
preparation. The reduction requirements are designed to satisfy the mechanical
principles, address the pulpal concerns, and preserve the structural requirements
of the tooth. The biologic zone can be developed by using the total dentogingival
complex measurements and will clinically aid in the determination of cervical
limitations to providing intracrevicular margin location.
PMID- 9656931
TI - The Tenax Dental Implant System. Rationalized implant treatment using
conventional prosthodontics.
PMID- 9656932
TI - Choosing the right clinical camera. Part I.
AB - Our recommendation is a 90-105 mm macro lens focusing from 1:1 to infinity and a
minimum aperture of f/32. A reputable brand should be preferred: Nikon, Canon,
Minolta, Sigma etc.... A 105 mm macro lens allows for adequate working distance
(approx. 130 mm for a straight view at 1:1 magnification). A 105 mm macro lens
induces insignificant perspective distortion and has a large range of aperture.
Lastly, it provides for a magnification scale ranging from 1:1 to infinity and is
optically excellent. The working distance of current camera systems extends
approximately from 4 4/8" or 114 mm, to 7" or 180 mm, at 1:1 magnification. Again
these differences are mainly due to lens design and mounted components, (filters,
bracket, lighting systems). A minimum of 5" or 125 mm of working distance is
desirable for physical access of your camera and proper illumination of the
photographed object. However, adequate lighting also depends upon the type and
location of your lighting system especially for higher magnification photographs.
Part II will examine the different lighting systems on the market and try to
decide which is most adapted to your needs. It will answer your questions about
the use of the operatory light while focusing, the red eye problem and the use of
polarizing filters to decrease the amount of reflection from the flash.
PMID- 9656933
TI - A five year study. Fluoride release of four reinforced composite resins.
AB - PURPOSE: The purpose of this study was to record the fluoride released measured
in parts per million of four fluoride composite resins for five years. MATERIALS
AND METHODS: Four fluoridated composites were separated into four groups. Two
composite resins with high viscosity were core materials, Ti-Core with titanium
(group 1) and Ti-Core Natural (group 2) and the other two resins studied were low
viscosity post cements Flexi-Flow cement with titanium (group 3) and Flexi-Flow
Natural (group 4). The fluoride release was studied under four experimental
conditions. Three replications were studied in each condition. Fluoride release
was measured for 260 weeks (5 years). STATISTICAL METHODS: A one-way analysis of
variance (ANOVA) was used to compare the average weekly release followed by a
Student-Newman-Keuls (SNK) pairwise multiple comparison test. All results were
considered statistically significant if p < 0.05. RESULTS: The ANOVA analysis
released a significant statistical interaction between group and week (p <
0.0001). Further analysis showed that the average weekly release for Ti-Core with
titanium did not differ from Ti-Core Natural, and that Ti-Core with titanium and
Ti-Core Natural differed from both Flexi-Flow Natural and Flexi-Flow with
titanium, which were not different from one another. CONCLUSIONS: Ti-Core with
titanium (Group 1) and Ti-Core Natural (Group 2) released a greater amount of
fluoride than Flexi-Flow with titanium (Group 3) and Flexi-Flow Natural (Group
4). The fluoride released from these fluoridated resin composites are similar to
reported ranges of other fluoride releasing dental restoration materials.
PMID- 9656934
TI - Profiting from restorative dentistry.
PMID- 9656935
TI - Infectious diseases: their impact on dentistry.
PMID- 9656936
TI - The MGDS examination: a systematic approach. 2. Part II of the examination: log
diary presentation, patient selection and assessment.
AB - This paper is the second in a series of four which present a systematic approach
to colleagues who are preparing for and sitting the examination for the Diploma
of Membership in General Dental Surgery (MGDS) of The Royal College of Surgeons
of England. Although some details may differ, the general principles set out in
the four papers apply equally to the MGDS examinations of the other Royal
Surgical Colleges.
PMID- 9656937
TI - The correlation between selected factors which influence dental aesthetics.
AB - This study evaluated the inter-relationship between five aesthetic factors: the
form of the face, tooth and arch, maxillary anterior tooth arrangement and
palatal contour. An assessment was made to determine if correlation was
sufficient to recommend their use as reliable aesthetic factors for the selection
of suitable tooth moulds for edentulous and partially edentulous patients. This
would enable the clinician to select a tooth mould at the chairside, based on an
evaluation of the individual's aesthetic factors where, for example, the
maxillary incisors should have the same outline shape as the individual's face. A
computer program was developed incorporating images of the factors taken from 50
Caucasian adults aged 20-31 years and assessment of correlation made by outline
superimposition and classification. The objectives were to design a computer
program to analyse, classify and evaluate correlation between the five factors in
each case by superimposition and classification. Correlation by superimposition
recorded some concurrence between forms. The findings of this study suggest that
there was insufficient correlation to support Nelson's 'Aesthetic Triangle', or
Williams' face form/tooth theory. The incidence of correlation by classification
between anterior tooth arrangement and arch form was sufficiently high to suggest
their value as an aesthetic aid.
PMID- 9656938
TI - Transverse expansion in the upper arch.
AB - The decision as to when to refer patients with transverse problems and when to
undertake expansion can be confusing. This paper explains the situations when
expansion should be undertaken and also covers the methods of treatment currently
available.
PMID- 9656939
TI - Biocompatibility of dentine-bonding agents. 2. Pulpal considerations.
AB - The paper reviews the literature concerning the biocompatibility of dentine
bonding agents. The literature review indicates that two main hypotheses are
presented to explain pulpal inflammation following the placement of materials
such as dentine-bonding agents, namely material toxicity and bacterial infection.
The paper discusses the role of such factors as microbial microleakage, remaining
dentine thickness and the smear layer as factors in determining material toxicity
and summarises the reported biocompatibility studies. From this it is concluded
that most bonding agents contain constituents which have a potential irritant or
toxic effect on the pulpo-dentinal complex. The irritant effect may be due to
constituents of the bonding agents, or to poor or lost bonding, or to a
combination of all these factors. The recently favoured total-etch technique may
cause an increase in dentine permeability by removal of the smear layer and
thereby increase the irritant effect of some materials.
PMID- 9656940
TI - The impact of computers in dental education.
AB - Computer technology is increasingly influencing many aspects of our lives and
will continue to do so in the future. This paper discusses the impact of
computers in dentistry; how their use is radically changing the way practices are
run and the way under/postgraduate dental education is evolving, by incorporating
computer-aided learning (CAL) material as an efficient and convenient educational
tool. Greater computer literacy may result in a future where there is a shift
away from traditional centres of learning to computer conferencing and distance
learning.
PMID- 9656941
TI - Evaluation of chest pain in low-risk patients presenting to the emergency
department: the role of immediate exercise testing.
AB - STUDY OBJECTIVES: To determine the safety and utility of immediate exercise
testing in the evaluation of low-risk patients presenting to the emergency
department with chest pain and its applicability to a heterogeneous population of
men and women. METHODS: We conducted a prospective study of the safety and
utility of immediate exercise testing in low-risk patients, as indicated by
clinical and ECG criteria. The study group was large, heterogeneous, and included
patients with a history of coronary artery disease. The patients were treated at
a large, university medical center. Exercise testing (immediate exercise
treadmill testing) was performed by internists, and cardiac serum enzyme levels
were not measured before the exercise test. RESULTS: A total of 212 patients (121
men, 91 women) underwent exercise testing with no adverse effects. Twenty-eight
(13%) patients had positive results on exercise ECGs. Twenty-three of the latter
had further evaluation that revealed evidence of coronary artery disease in 13
(57%). Fifty-nine percent (125/212) of patients had negative exercise test
results and 28% (59/212) had nondiagnostic tests. All patients with negative test
results and 93% with nondiagnostic test results were discharged directly from the
ED. Thirty-day follow-up was achieved in 201 (95%) patients and revealed no
mortality in any of the patients in the three groups. One patient with a positive
exercise test result returned to the ED within 30 days with mild congestive heart
failure. CONCLUSION: Our results in this patient population support the safety
and utility of immediate exercise testing of low-risk patients who present to the
ED.
PMID- 9656942
TI - Multicenter comparison of two clinical decision rules for the use of radiography
in acute, high-risk knee injuries.
AB - STUDY OBJECTIVE: Two separate clinical decision rules, one developed in Ottawa
and the other in Pittsburgh, for the use of radiography in acute knee injuries
have been previously validated and published. In this study, the rules were
prospectively validated and compared in a new set of patients. METHODS: A
prospective, blinded, multicenter trial was conducted in the emergency
departments of three urban teaching hospitals. A convenience sample of 934
patients with knee pain requiring radiographs was enrolled. A standardized data
form was completed for each patient, comprising the 10 clinical variables
included in the two rules. Standard knee radiographs were then taken in each
patient. The rules were interpreted by the primary investigator on the basis of
the data sheet and the final radiologist radiograph reading. RESULTS: In the 745
patients in whom the Pittsburgh rules could be applied there were 91 fractures
(12.2%). The use of the Pittsburgh rule missed one fracture, yielding a
sensitivity of 99% (95% confidence interval [CI], 94% to 100%); the specificity
was 60% (95% CI, 56% to 64%). The Ottawa inclusion criteria were met by 750
patients, with 87 fractures (11.6%). The Ottawa rule missed three fractures, for
a sensitivity of 97% (95% CI, 90% to 99%); specificity was 27% (95% CI, 23% to
30%). CONCLUSION: Prospective validation and comparison found the Pittsburgh rule
for knee radiographs to be more specific without loss of sensitivity compared
with the Ottawa rule.
PMID- 9656943
TI - Validation of the Ottawa ankle rules in France: a study in the surgical emergency
department of a teaching hospital.
AB - STUDY OBJECTIVE: To validate the Ottawa ankle rules to predict fractures in a
French clinical setting when they are used by physicians not involved in their
development. METHODS: We used a prospective patient survey by emergency
physicians in a surgical emergency department of a university teaching hospital
of the Assistance Publique-Hopitaux de Paris. The study group consisted of 416
consecutive patients aged 18 years and older who presented with acute ankle or
midfoot injuries in the surgical ED during a 4-month period. Radiography was
performed in each patient after clinical evaluation findings were recorded.
RESULTS: Forty-nine ankle and 22 midfoot fractures were diagnosed. The decision
rules had a sensitivity of .98, a specificity of .45, and a negative predictive
value of .99 in detecting ankle fractures, a sensitivity of 1.0, a specificity of
.29, and a negative predictive value of 1.0 in detecting midfoot fractures. The
rules failed to predict one avulsion fracture in the ankle group. Application of
these rules by emergency physicians would have reduced ankle or midfoot
radiography requests by 33%. CONCLUSION: Use of the Ottawa ankle rules by French
emergency physicians not involved in the rules' development resulted in 99%
sensitivity and had a potential of reducing radiography requests by 33%.
PMID- 9656944
TI - Factors influencing hospital transport of patients in continuing cardiac arrest.
AB - STUDY OBJECTIVE: Prior research has established the futility of continued
resuscitation efforts for patients in cardiac arrest who fail to respond to out
of-hospital advanced cardiac life support. Determination of both medical and
nonmedical factors resulting in the transport of patients in continuing cardiac
arrest to the hospital may encourage the development of new systems or strategies
to increase the appropriateness of these transports. METHODS: The attending
paramedic completed a prospective survey after unsuccessful resuscitation efforts
in our urban, hospital-based, two-tier emergency medical services (EMS) system.
All nontraumatic adult arrests were included unless they were clearly noncardiac
in nature. RESULTS: Paramedics responded to 259 cardiac arrests between September
12, 1996, and April 31, 1997. Seventy-nine patients were pronounced dead without
resuscitation efforts. Of the remaining 180 patients, 44 had return of
spontaneous circulation and were transported to the hospital, 68 were pronounced
dead in the field, and 68 were transported to the hospital in continuing cardiac
arrest. The 68 patients transported while in cardiac arrest are the focus of this
study. Rare problems with field termination were identified. Reasons for
transport of the 68 patients in continuing cardiac arrest included arrest in
ambulance or going to ambulance (n = 6), arrest in a public place (n = 17),
environmental factors (n = 6), road hazard to paramedics (n = 1), possible
reversible cause (n = 4), persistent ventricular dysrhythmia (n = 5), no
intravenous access (n = 5), airway difficulties (n = 5), family unable to accept
field termination (n = 3), cultural or language barrier (n = 1), EMS physician
ordered transport (n = 1), and obesity (n = 1). A protocol allowing pronouncement
of death in the ambulance and transport of the body to a designated area could
have prevented lights-and-siren transport to the emergency department in 24 of
the 68 cases. CONCLUSION: Factors other than medical ones often influence the
decision to transport patients in continuing cardiac arrest. In our urban system,
physician, medical examiner, and paramedic education and protocols were needed to
aid decision-making in this situation.
PMID- 9656945
TI - Prehospital oral endotracheal intubation by rural basic emergency medical
technicians.
AB - STUDY OBJECTIVE: To determine whether basic emergency medical technicians (EMT-B)
can perform prehospital oral endotracheal intubation with success rates
comparable to those of paramedics. METHODS: This was a nonrandomized, controlled
trial using historical controls. Seven basic life support emergency medical
services systems in six counties and their corresponding emergency departments in
rural Indiana participated. Eighty-seven full-time EMTs with no prior or
concurrent paramedic training volunteered for intubation training. Apneic
prehospital patients aged 16 years or older without an active gag reflex or
massive facial trauma were eligible for intubation and study enrollment. The EMTs
completed a 9-hour didactic and airway manikin training course in direct
laryngoscopic endotracheal intubation. The course was adapted from the national
paramedic curriculum. RESULTS: Thirty-four (39%) of the EMT-Bs attempted to
intubate 57 eligible patients. In 49.1% of these patients, successful
endotracheal tube placement was confirmed by the receiving physician (95%
confidence interval, 36.4% to 61.9%); in contrast, the prehospital intubation
success rates from three previous studies of manikin-trained paramedics ranged
from 76.9% to 90.6% (P < .001). Complications included five (9%) inadvertent
extubations, two endotracheal tube cuff ruptures, two prolonged intubation
attempts, and one mainstem bronchus intubation. There were no unrecognized
esophageal intubations. Two of the seven EMS agencies did not report any
intubation data. CONCLUSION: Rural EMTs with didactic and airway manikin training
failed to achieve prehospital intubation success rates comparable to those of
paramedic controls. Possible explanations include training deficiencies, poor
skill transference from manikin to human intubation, infrequent intubation
experiences, and inconsistent supervision.
PMID- 9656946
TI - Prospective field study of violence in emergency medical services calls.
AB - STUDY OBJECTIVE: To investigate the nature and frequency of violence encountered
by EMS personnel. DESIGN: We conducted a prospective, observational case-series
study of a city-county EMS system serving a population of 500,000. RESULTS: We
analyzed 297 EMS runs over 737 hours of observation. The Overt Aggression Scale
(OAS) was used to assess each violent episode. There were 239 (81%) nonviolent
runs, 16 (5%) violent runs, and 42 (14%) violent runs that occurred after a
violent episode had taken place (postviolent runs). This was a frequency of one
violent episode for every four 12-hour shifts, or for every 19 runs. The violent
behaviors included verbal aggression solely in 50% (n = 8), physical aggression
solely in 13% (n = 2), and both verbal and physical aggression in 38% (n = 6).
One episode involved an unsecured weapon. CONCLUSION: These data indicate that
violent situations occur in 5% of calls in this EMS system. The fact that an
additional 14% of calls are precipitated by the results of violence may influence
perceptions by EMS personnel of danger and frequency of exposure to unstable
situations. Exposure to violence is underreported in our EMS documentation.
PMID- 9656947
TI - Trends in firearm-related injuries in Washington State, 1989-1995.
AB - STUDY OBJECTIVES: To describe the incidence and outcome of firearm-related
injuries and to describe trends over time. DESIGN: Information about firearm
related injuries in Washington state was extracted from computerized death
certificate and hospital discharge files for the period 1989 through 1995. Cases
seen only in emergency departments were estimated using initial results from a
statewide firearm injury surveillance system. RESULTS: An estimated 9,995 persons
were shot during the 7-year period (incidence 28.0/100,000 person-years); 2,944
persons (29%) required ED care only, 2,864 persons (29%) were hospitalized and
survived, and 4,187 persons (42%) died. Survival was lowest for suicide attempts
(11%), intermediate for assaults (68%), and greatest for unintentional shootings
(96%). Most deaths (91%) occurred before hospital admission. From 1989 to 1995,
the incidence of firearm-related injuries showed little change: an increase of
4.5%. However, suicidal shootings among persons younger than 35 years increased
by 31.3%, and the incidence of firearm-related assaults rose by 53.7% among
persons of all ages. Survival among all persons who were shot and among
hospitalized shooting victims showed little change over time. CONCLUSION: Firearm
related suicides among the young and assault-related shootings among all persons
increased. The estimated proportion of shooting victims who survived did not
change over time.
PMID- 9656948
TI - Criminal activity and assault-type handguns: a study of young adults.
AB - STUDY OBJECTIVE: We studied a population of young adults who legally purchased
handguns to determine whether an association exists between the purchase of an
assault-type handgun and prior or subsequent criminal activity. METHODS: We
conducted a longitudinal study of 5,360 legally authorized purchasers of handguns
in California in 1988 who were younger than 25 years at the time of purchase. Our
main outcome measures were (1) adjusted relative risk (RR) for the purchase of an
assault-type handgun for subjects with a criminal history compared with subjects
without such a history and (2) adjusted RR for new criminal activity during the 3
years after handgun purchase for purchasers of assault-type handguns compared
with purchasers of other handguns. RRs were adjusted for sex and race/ethnicity.
RESULTS: Handgun purchasers with a criminal history were more likely than those
with no criminal history to purchase assault-type handguns (4.6% and 2.0%,
respectively; RR = 2.0; 95% confidence interval [CI] 1.5 to 2.8). Among handgun
purchasers who had a criminal history, purchasers of assault-type handguns were
more likely than purchasers of other handguns to be charged with new offenses (RR
= 1.5; 95% CI, 1.3 to 1.9), including offenses involving firearms of violence (RR
= 1.7; 95% CI, 1.3 to 2.20. Among those who had previously been charged with
Violent Crime Index offenses (murder, rape, robbery, aggravated assault), those
who purchased assault-type handguns were more than twice as likely as purchasers
of other handguns to be charged with a new offense (RR = 2.3; 95% CI, 1.5 to 3.4)
and three times as likely to be charged with a new offense involving firearms or
violence (RR = 3.0, 95% CI, 1.9 to 4.6). CONCLUSION: In this population, the
purchase of an assault-type handgun was associated with both prior and subsequent
criminal activity.
PMID- 9656949
TI - Trends in nonfatal and fatal firearm-related injury rates in the United States,
1985-1995.
AB - STUDY OBJECTIVE: To characterize trends in annual estimates of nonfatal firearm
related injuries treated in US hospital emergency departments and to compare
trends in quarterly rates of such injuries with those of firearm-related
fatalities in the US population. METHODS: Data on nonfatal firearm-related
injuries were obtained from the National Electronic Injury Surveillance System
(NEISS) by review of medical records for June 1, 1992, through May 31, 1995. Data
on firearm-related fatalities were obtained from the National Vital Statistics
System for January 1, 1985, through December 31, 1995. NEISS comprises 91
hospitals that represent a stratified probability sample of all hospitals in the
United States and its territories that have at least six beds and provide 24-hour
emergency service. The main outcome measures were numbers, percentages, and
quarterly population rates for nonfatal and fatal firearm-related injuries.
RESULTS: An estimated 288,538 nonfatal firearm-related injuries (95% confidence
interval [CI], 169,776 to 407,300) were treated in EDs during the 3-year study
period. The annual number of non-fatal firearm-related injuries increased from
99,025 for June 1992 through May 1993 (95% CI, 58,266 to 139,784) to 101,669 for
June 1993 through May 1994 (95% CI, 59,822 to 143,516), then decreased to 87,844
for June 1994 through May 1995 (95% CI, 51,687 to 124,001). Before the third
quarter of 1993, quarterly nonfatal and fatal firearm-related injury rates in the
total US population and quarterly nonfatal firearm assaultive injury and firearm
homicide rates for males aged 15 to 24 years were observed to be on the rise.
Since then, these rates have significantly declined. CONCLUSION: Analysis of
national trends indicates that non-fatal and fatal firearm-related injuries are
declining in the United States, although the rate of firearm-related deaths
remains high, especially among males aged 15 to 24 years, in relation to other
leading causes of injury death. An assessment of factors responsible for the
decline in firearm-related injuries is needed to design further prevention
efforts.
PMID- 9656950
TI - Handgun purchase trends, Washington state: differences by age of buyer.
AB - STUDY OBJECTIVES: To examine trends in legal handgun purchases from federally
licensed dealers and specifically to describe recent changes in age and gender of
purchaser and caliber of handguns purchased. METHODS: A cohort study was
performed of the adult population of Washington state from 1950 through 1992
using a state dealer record of handgun sales database. The purchase of handguns
from licensed dealers was expressed as the number purchased per 100,000
population per year. RESULTS: The handgun purchase rate increased for the total
population between 1950 and 1992, from 169 to 2,076 per 100,000 persons. Between
1983 and 1992, the purchase rate among men aged 21 to 24 years increased 184%;
among women of this age group, the rate increased 127%. Among men aged 21 to 24
years, the rate of 9 mm handgun purchases increased 1,682% between 1983 and 1992,
the greatest increase for any age-caliber category. CONCLUSION: The greatest
increase in rate of legal handgun purchases in Washington state from 1983 through
1992 was among the youngest purchasers. Sales of 9 mm handguns increased most
rapidly, especially among the youngest buyers.
PMID- 9656951
TI - The next-generation emergency department.
AB - The greatest advances in medicine over the next two decades will result from
application of the tools and principles of informatics to the problems of
clinical medicine. New developments in medical informatics will drive advances in
clinical care administration, research, and education. Information flow in the
emergency department a decade hence will be characterized by a transformation
from a "hunter-gatherer" information model to a "publisher-subscriber" model in
which the right information will always be available at the right time. In large
part, information will be gathered automatically rather than manually. Computers
will be ubiquitous and almost invisible. Invasive and attached monitoring and
testing will yield to new remote and noninvasive technologies. Information will
be shared and modified as needed, rather than recreated and reentered by each
caregiver. Eventually, the use of information technologies in the emergency
medicine workplace will enhance our traditional role as hands-on providers of
direct patient care.
PMID- 9656952
TI - EM3M: envisioning the future of emergency medicine.
PMID- 9656953
TI - Preventing firearm injuries.
PMID- 9656954
TI - ACEP endorsement of the EAST position paper on firearms violence.
PMID- 9656955
TI - Emergency medicine in Hong Kong.
AB - Emergency medicine in Hong Kong is a relatively new specialty. Substantial
progress toward recognition of emergency medicine in the territory has occurred
during the past 2 years, and the Hong Kong College of Emergency Medicine is now
formally recognized by the Royal College of Surgeons in the United Kingdom. With
the transfer of the territory to chinese rule, the emergency medical system in
Hong Kong may serve as a model for the development of emergency medicine in
mainland China.
PMID- 9656956
TI - United States physician assistance in development of emergency medicine in
Hangzhou, China.
AB - Emergency medicine is growing rapidly as a specialty and is beginning to be
recognized as an essential component of medicine in China. Traditional Chinese
medicine and modern technology exist together. A description of the US authors'
experience as consultants at a new emergency department and in establishing an
emergency medicine residency program in Hangzhou, China is provided. A total of 7
months were spent in the observation, identification, and development of a basic
framework of emergency care at a new hospital. The practice of emergency medicine
in China was researched by direct observation at several Chinese cities and by
literature review. China is taking the parts of the Western system it can use and
implementing its own methods in the overall practice of emergency medicine.
PMID- 9656957
TI - Emergency medicine in Thailand.
AB - Typical of developing countries, Thailand, located in Southeast Asia, is only
beginning to consider the importance of emergency medicine and prehospital care.
Medical emergencies in Thailand have traditionally had relatively high rates of
occurrence and are currently increasing in the context of rapid economic
development and urbanization, yet no formal emergency care training for
physicians or prehospital care workers exists.
PMID- 9656958
TI - Acute right lower quadrant pain in a patient with leukemia.
AB - Typhlitis or neutropenic enterocolitis is a life-threatening, necrotizing process
of the cecum whose incidence is increasing. It is usually encountered in patients
with leukemia who have recently undergone chemotherapy. Neutropenic enterocolitis
presents as fever, abdominal pain, and diarrhea in neutropenic patients. As the
incidence of neutropenic enterocolitis increases, emergency physicians must be
aware of this rapidly progressive and potentially fatal disease.
PMID- 9656959
TI - Dexfenfluramine overdose.
AB - Dexfenfluramine (Redux), the dextro-rotatory (+) steroisomer of fenfluramine, was
previously approved for the treatment of weight control in the United States. We
report a case of acute dexfenfluramine ingestion characterized by coma, clonus,
and respiratory failure.
PMID- 9656960
TI - Hyperkalemic ascending paralysis.
AB - Hyperkalemia is a life-threatening electrolyte disturbance. The clinical
presentation is most commonly related to its effects on cardiac conductivity and
contractility, although weakness and respiratory compromise may occur. We
describe what we believe to be the first reported case of life-threatening
hyperkalemia presenting as an ascending paralysis which was associated with
standard-dose trimethoprim-sulfamethoxazole therapy. The patient had mild,
underlying renal disease which predisposed him to develop hyperkalemia. This case
underscores the need to use caution in prescribing trimethoprim to such patients.
PMID- 9656961
TI - Update: human ehrlichiosis--Maryland and Wisconsin, 1994.
PMID- 9656962
TI - Universal health care: associated factors.
PMID- 9656963
TI - Guidelines for care of the elderly.
PMID- 9656964
TI - Guidelines for care of the elderly.
PMID- 9656965
TI - Guidelines for care of the elderly.
PMID- 9656966
TI - Positional asphyxia.
PMID- 9656967
TI - Bull-riding injuries.
PMID- 9656968
TI - Clinical management of early progressive renal failure.
AB - In the era of managed health care, the primary physician will be required to play
an active role in the management of patients with early renal failure. This
section provides a comprehensive and practical approach to the management of such
patients. Early recognition of renal failure and monitoring its progression
require an understanding of the pitfalls of commonly used diagnostic tests. Tight
control of hypertension, angiotensin-converting enzyme inhibition, and dietary
protein restriction play important roles in delaying the progression of renal
disease. Avoidance of additional renal insults such as nephrotoxic drugs and
radiographic contrast prevents acceleration of renal demise. A variety of
clinical manifestations, including dyselectrolytemias, hypertension,
malnutrition, secondary hyperparathyroidism, and anemia may develop in patients
with early renal failure. Timely referral to a nephrologist will facilitate
planning for renal replacement therapy and may favorably affect eventual
outcomes.
PMID- 9656969
TI - Nephrolithiasis: acute management and prevention.
AB - The primary care physician has a responsibility not only to recognize and treat
acute stone passage but to ensure that the patient with recurrent stones has
metabolic evaluation and appropriate preventive care. Renal colic is typically
severe, radiates to the groin, is associated with hematuria, and may cause ileus.
About 90% of stones that cause renal colic pass spontaneously. The patient with
acute renal colic should be treated with fluids and analgesics and should strain
the urine to recover stone for analysis. Highgrade obstruction or failure of oral
analgesics to relieve pain may require hospitalization; a urinary tract infection
in the setting of an obstruction is a urologic emergency requiring immediate
drainage, usually with a ureteral stent. Several approaches are available when
stones do not pass spontaneously, including extracorporeal shock wave
lithotripsy, percutaneous lithotripsy, and ureteroscopic laser lithotripsy.
Calcium stone disease has a lifetime prevalence of 10% in men and causes
significant morbidity. Renal failure is unusual. Stone types include calcium
oxalate, uric acid, struvite, and cystine. Stone analysis is particularly
important when a noncalcareous constituent is identified. The majority of
patients with nephrolithiasis will have recurrence, so prevention is a high
priority. High fluid intake is a mainstay of prevention. Metabolic evaluation
will indicate other appropriate preventive measures, which may include dietary
salt and protein restriction, and use of thiazide diuretics, neutral phosphate,
potassium citrate, allopurinol, and magnesium salts. Dietary calcium restriction
may worsen oxaluria and negative calcium balance (osteoporosis).
PMID- 9656970
TI - Diabetic nephropathy.
AB - Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD)
and accounts for 35% of the ESRD population in the United States. It results in
considerable morbidity, mortality, and expense. The average cost of managing one
diabetic patient with ESRD is approximately $50,000 a year. Over the last decade,
several advances in the management of diabetic nephropathy have allowed
physicians to intervene and retard the progression of renal failure in patients
with diabetic nephropathy. Stalling the progression of renal failure allows
patients to maintain a superior quality of life and saves society millions of
dollars that can be allocated to other aspects of health care. The prevalence of
diabetes mellitus continues to increase. With the continued advances in medical
technology and care, persons with this disease will live longer, and the
incidence of diabetic nephropathy will increase. Primary care physicians will
have the most frequent contact with these patients and therefore will have the
greatest potential to favorably affect their clinical course. This review focuses
on the therapeutic interventions available to delay the progression of diabetic
nephropathy. Clinicians should strive to secure euglycemia and obtain optimal
blood pressure control in their patients. The unique renal-protective effects of
angiotensin-converting enzyme inhibitors will be reviewed, as will the salutary
effects of a low-protein diet, normalizing serum cholesterol, and the cessation
of smoking. The optimal timing of dialysis access placement and the initiation of
dialysis and transplantation will also be discussed.
PMID- 9656971
TI - PET imaging studies in drug abuse.
AB - In spite of the massive public health problem associated with drug abuse,
effective treatments remain elusive. This is due in part to a relatively poor
understanding of the neurochemical changes which drugs of abuse produce in the
human brain and the relationship of these changes to the behavioral and addictive
properties of drugs. With the development of modern imaging methods and a variety
of labeled drugs and radiotracers, it has now become possible to track many
aspects of drug pharmacokinetics and pharmacodynamics directly in the human brain
and to relate these parameters to the behavioral and toxic properties of drugs.
REVIEW: In this article, we will highlight some examples of the use of Positron
Emission Tomography to measure drug pharmacokinetics and pharmacodynamics and
their relationship to addiction and to toxicity.
PMID- 9656972
TI - Prognostic factors in patients with methanol poisoning.
AB - OBJECTIVE: To identify prognostic factors in methanol poisoning and determine the
effect of medical interventions on clinical outcome. METHODS: Retrospective
review of all patients treated for methanol poisoning from 1982 through 1992 at
The Toronto Hospital. Presenting history, physical examination, results of
laboratory tests, medical interventions, and final outcomes after hemodialysis
were abstracted. RESULTS: Of 50 patients treated for methanol poisoning, 18 (36%)
died, 32 (64%) survived. Seven of the 32 survivors sustained visual sequelae
(22%), the remaining 25 (78%) recovered completely. Patients presenting with coma
or seizure had 84% (16/19) mortality compared to 6% (2/31) in those without (p <
0.001). Initial arterial pH < 7 was also associated with significantly higher
mortality (17/19, 89% vs 1/31, 3%, p < 0.001). There were no differences in time
from presentation to dialysis between survivors and fatalities (8.4 +/- 3.6 vs
7.6 +/- 3.5 hours, p = 0.47). The deceased patients had higher mean methanol
concentration than the survivors (83 +/- 53 vs 41 +/- 25 mmol/L, p = 0.004).
Subgroup analysis of 19 patients presenting with visual symptoms who survived
showed prolonged acidosis (5.4 +/- 2.3 vs 3.0 +/- 2.1 hours, p = 0.06) in those
with persistent visual sequelae. CONCLUSIONS: Coma or seizure on presentation and
severe metabolic acidosis, in particular initial arterial pH < 7, are poor
prognostic indicators in methanol poisoning. Survivors presented with lower
methanol concentrations. Patients with residual visual sequelae had more
prolonged acidosis than those with complete recovery. Future studies will be
needed to confirm the effect of correction of acidosis on final clinical outcome.
PMID- 9656973
TI - A preliminary study of immunologic and hematologic profiles of peripheral blood
from Nebraska farmers who apply pesticides to their fields.
AB - OBJECTIVE: Laboratory studies have documented a wide range of pesticide-induced
changes in the hematopoietic and lymphoreticular systems. Some of these are
expressed as altered serum values, blood cell counts, and leucocyte functions.
The goal of the present study was to determine whether these alterations were
evident in peripheral blood of Nebraska farmers who applied pesticides to their
fields. METHODS: An invitation to participate was mailed to 100 residents (70
farmers; 30 controls) of Butler County, Nebraska. All respondents (51 farmers and
21 controls) were enrolled and surveyed by written questionnaire for health
status and pesticide use. Our analysis included 45 farmers and 18 controls. The
farmers were divided into a high (n = 23) and a low (n = 22) pesticide use group.
Statistical correlations of ten blood values with both pesticide use and age were
evaluated, since pesticide use correlated with age. RESULTS: Four of the ten
blood values correlated with pesticide use and age (Spearman Rho). In a multiple
regression model, pesticide use (not age) proved to be a predictor of red blood
cell count and hematocrit. In the same model, pesticide use was not a predictor
of mean red cell volume or candida antigen-induced T-lymphocyte proliferation.
Serum complement activity did not correlate with pesticide use among the farmers
(n = 45) but was significantly reduced (ANOVA) in the high pesticide use group,
compared to controls. CONCLUSIONS: A preliminary study of blood values in a small
cohort of Nebraska farmers found no pesticide-associated effects on 1) leucocyte
count, 2) antigen- and mitogen-stimulated T-cell proliferation, 3) mitogen
stimulated B-cell proliferation, and 4) concentrations of serum IgG and IgM. The
study found small but statistically significant pesticide-associated effects on
red blood cells and serum complement.
PMID- 9656974
TI - Zolpidem-associated hallucinations and serotonin reuptake inhibition: a possible
interaction.
AB - BACKGROUND: Zolpidem (Ambien) is a sedative believed to act exclusively at the
benzodiazepine omega 1 receptor. Sporadic case reports of zolpidem-associated
hallucinations have appeared over the past 5 years, and over the past 2 years,
the Washington Poison Center received five reports of prolonged visual
hallucinations associated with zolpidem. CASE REPORTS: All five patients reported
experiencing visual hallucinations lasting from 1-7 hours soon after taking
zolpidem. Most had been taking zolpidem for less than a week and all five were
concurrently taking an antidepressant: sertraline, desipramine, fluoxetine,
bupropion, or venlafaxine; two sought assistance at a hospital. DISCUSSION: The
precise mechanism of zolpidem-associated hallucinations remains unknown. In some
previously published cases, the zolpidem-associated hallucinations have been
short in duration, lasting at most 30 minutes. In contrast, the five patients in
our series and in five previously reported cases, the hallucinations were more
persistent, lasting up to 7 hours. Of these ten cases with persistent symptoms,
nine were concurrently taking antidepressants that inhibit serotonin-reuptake,
despite the fact that zolpidem has no known serotonin-mediated mechanisms.
CONCLUSIONS: These cases, plus prior case reports, suggest that a pharmacodynamic
interaction between serotonin reuptake inhibition and zolpidem may lead to
prolonged zolpidem-associated hallucinations in susceptible individuals.
PMID- 9656975
TI - Poisoning severity score. Grading of acute poisoning.
AB - BACKGROUND: A standardized and generally applicable scheme for grading the
severity of poisoning allows a qualitative evaluation of morbidity and
facilitates comparability of data. Working from a simple grading scale proposed
by the European Association of Poisons Centres and Clinical Toxicologists, a
Poisoning Severity Score has been developed jointly with the International
Programme on Chemical Safety and the European Commission. METHODS: The Poisoning
Severity Score has been elaborated, tested, and gradually revised during a
project running 1991-1994. Fourteen poisons centers from various countries have
participated. Each center independently graded 371 cases of acute poisoning by
ten different toxic agents. The data were then analyzed and compared. RESULTS:
The concordance in grading the severity increased during the study period, and in
the last phase there was an acceptable concordance among centers in 80% or more
of the cases. Given the condition and quality of the original case records, this
result was considered satisfactory and agreement was reached on the scoring
scheme presented here. The Poisoning Severity Score grades severity as (0) none,
(1) minor, (2) moderate, (3) severe, and (4) fatal poisoning. It is intended to
be an overall evaluation of the case, taking into account the most severe
clinical features. Use of the Poisoning Severity Score normally requires a follow
up of all cases, but may be used on admission or other times during the course of
poisoning if this is clearly stated when data are presented. CONCLUSIONS: A
Poisoning Severity Score has been developed and found applicable for grading the
severity of poisoning. It is foreseen that the Poisoning Severity Score will meet
the expectations and be used in practice, but its future use and evaluation may
result in some further revision and refinement.
PMID- 9656976
TI - The prospective value of the IPCS/EC/EAPCCT poisoning severity score in cases of
poisoning.
AB - INTRODUCTION: The poisoning severity score is a four-point severity
classification scale, developed by the International Programme on Chemical
Safety, the Commission of the European Union, and the European Association of
Poison Centres and Clinical Toxicologists (IPCS/EC/EAPCCT), for the retrospective
assessment of cases of poisoning reported to poisons information centers.
OBJECTIVES: The aims of this study were to test the validity of using the
poisoning severity score obtained at initial referral to assess clinical severity
and the likelihood of subsequent deterioration, to select cases for follow-up,
and also to determine the need for referral to a clinical toxicologist. METHODS:
The poisoning severity score was determined at the time of initial inquiry.
Follow-up was then undertaken until either the patient was discharged from
medical attention or died. A second poisoning severity score was then calculated
taking note of the most severe features present after the initial inquiry.
RESULTS: Of 718 consecutive telephone inquiries, 397 were given an initial
poisoning severity score of 0 (no signs and symptoms), 225 a score of 1 (mild
symptoms), 71 a score of 2 (moderate symptoms), and 25 a score of 3 (severe
symptoms). Follow-up data are available only in 638 cases because the patient or
referring doctor could not be traced in 80 instances. Of the 638 cases, 41
deteriorated; 31 of these were graded initially as poisoning severity score 0,
four as 1, and six as 2. Five patients died (two with an initial score of 2 and
three with an initial score of 3). CONCLUSIONS: This study demonstrates that it
is useful to score telephone inquiries to a poisons information service at
initial referral with the poisoning severity score. First, the poisoning severity
score is helpful in assessing accurately the clinical severity and the likelihood
of further deterioration. Second, the poisoning severity score is useful in
determining the need for referral of the inquiry to a clinical toxicologist, thus
ensuring that more serious and complicated cases of poisoning receive expert
medical advice on management. Third, the poisoning severity score is helpful in
selecting those cases which warrant follow-up for medical and epidemiological
reasons.
PMID- 9656977
TI - Is the yew really poisonous to you?
AB - BACKGROUND: Taxus species, commonly referred to as yew plants, have the
reputation of being inordinately toxic. Case reports which chronicle human near
fatal yew berry ingestions and countless fatalities in livestock present a sober
profile to the treating toxicologist. Very often, a limited number of adverse
reports influence decisions on all exposures to that potential poison. The
objective of this investigation was to profile the toxicity of exposures to Taxus
spp and determine what percentage of exposures were associated with significant
morbidity. METHODS: The individual computerized files of all exposures to Taxus
spp were retrieved from American Association of Poison Control Centers (AAPCC)
Toxic Exposure Surveillance System (TESS) and placed in a relational database.
Reports from 1985-1994 were analyzed. The cases were examined to determine
patient demographics, the outcome of exposures, the ultimate disposition of the
patients, treatment, and symptoms. AAPCC TESS definitions were used to assess
outcomes. RESULTS: The number of exposures identified from the 10-year subset was
11,197. Children less than 12 years of age were involved in 96.4% (< 6 years
92.7%; 6-12 years, 3.7%) of the exposures. When the final outcome of the exposure
was documented (n = 7269), no adverse effects occurred in 92.5% and minor effects
were experienced in 7.0%. Moderate (more pronounced, but not life-threatening)
effects were experienced by 30 individuals and major (life-threatening) effects
occurred in 4 people. There were no fatalities. Decontamination therapy, when
compared to no therapy, had no impact on patient outcome. 6.3% were admitted for
psychiatric or medical care. When symptoms were related to Taxus spp exposures,
the most frequent symptoms were gastrointestinal (65.5%), followed by dermal
(8.3%), neurological (6.0%), and cardiovascular (6.0%). DISCUSSION: There are
limitations to the interpretation of AAPCC TESS data which may lead to bias in
favor of positive outcomes. However, the large sample size may minimize the
limitations. CONCLUSION: Taxus spp exposures result only rarely in significant
morbidity. Consistent with published case reports, the most common symptoms were
gastrointestinal. Decontamination had no impact on patient outcome.
PMID- 9656978
TI - Poison centers and plants: more pollyanna data?
PMID- 9656979
TI - Pediatric benzodiazepine ingestion resulting in hospitalization.
AB - OBJECTIVE: To characterize the clinical findings in children hospitalized for
benzodiazepine ingestion. METHOD: Retrospective case series in two urban
children's hospitals, with no intervention. Suicide attempts and polypharmacy
ingestions were excluded. RESULTS: Forty-six children (67% male) with a mean age
of 36 months (range 14-127 months) were hospitalized from January 1987 through
September 1994. Lorazepam was most frequently ingested (13/41 identified drugs,
32%). The most prevalent symptoms were ataxia (87%), lethargy (57%), coma
(Glasgow coma score < 15, 35%; Reed coma score > 0, 22%), and respiratory
depression (9%). Duration of symptoms was less than 24 hours in 88% of patients.
Isolated ataxia occurred in eight patients; in five of these patients,
benzodiazepine ingestion was unsuspected by the physicians. Three parents
intentionally administered the benzodiazepine to their child. Only 50% of 32
toxicology screens were positive for benzodiazepines. One child required
endotracheal intubation. Flumazenil administration preceded clinical improvement
in two other children. The remaining patients received activated charcoal
administration and supportive care. CONCLUSION: Children hospitalized for
benzodiazepine overdose occasionally had life-threatening symptoms. Ataxia was
the most common clinical finding following benzodiazepine ingestion in this
series. Flumazenil appeared beneficial for the treatment of severe benzodiazepine
toxicity in only two patients. Most children recovered from their overdose
uneventfully after receiving activated charcoal and supportive care.
PMID- 9656980
TI - Peripheral polyneuropathy due to chronic use of topical ammoniated mercury.
AB - BACKGROUND: Despite their potentially disastrous side effects, topical mercury
salts can still be found as ingredients in some over-the-counter preparations or
local remedies. CASE REPORT: Peripheral polyneuropathy as a result of chronic
ammoniated mercury poisoning was studied and followed over 2 years. A 36-year-old
man developed peripheral polyneuropathy following chronic perianal use of an
ammoniated mercury ointment. Highly elevated blood and urine mercury levels were
found. Sural nerve biopsy showed mixed axonal degeneration-demyelination. There
was progressive improvement of his symptoms over 2 years but neurophysiological
examination revealed incomplete recovery. CONCLUSION: The availability of safer
drugs should result in a complete ban of these dangerous compounds.
PMID- 9656981
TI - Massive sulfasalazine and paracetamol ingestion causing acidosis, hyperglycemia,
coagulopathy, and methemoglobinemia.
AB - CASE REPORTS: Reports of acute toxicity following sulfasalazine ingestion are
rare. A case of an acute ingestion of sulfasalazine 50 g and paracetamol 50 g
resulting in severe lactic acidosis, seizures, coagulopathy, hyperglycemia,
ketosis, and methemoglobinemia is reported. Despite the ingestion of a large
amount of paracetamol with serum paracetamol 5486 nmol/L (844 mg/L), significant
hepatotoxicity did not occur. The patient recovered fully following
administration of intravenous N-acetylcysteine, methylene blue, sodium
bicarbonate, and supportive therapy.
PMID- 9656982
TI - Fatality resulting from intraventricular vincristine administration.
AB - BACKGROUND: Inadvertent intrathecal administration of vincristine has been
reported and is uniformly fatal except in two of three cases treated with spinal
fluid exchange. We report a case of inadvertent direct intraventricular
vincristine administration. CASE REPORT: A 59-year-old woman developed acute
lymphocytic leukemia with meningeal involvement and was being treated with
intraventricular cytarabine (beta-cytosine arabinoside, Ara-C) injected via an
Ommaya reservoir, intravenous (i.v.) vincristine, prednisone, and i.v.
daunorubicin. The vincristine (2 mg in 10 mL diluent) was inadvertently injected
into her Ommaya reservoir. Within 10 minutes, the error was realized. Despite
optimal care, nausea and vomiting developed the first night, followed
sequentially by coarse tremor, disorientation, horizontal nystagmus, and stupor.
Her mental status waxed and waned until day 9, at which time she became
responsive only to noxious stimuli. By day 11, she was deeply comatose and on day
40 she died without regaining any neurological function. CONCLUSION: Despite
aggressive and immediate therapy, intraventricular vincristine infusion produced
neurologic toxicity, with progressive loss of mental function, followed by coma
and death. Systems need to be developed to prevent inadvertent central nervous
system administrations.
PMID- 9656983
TI - ECG changes and plasma concentrations of propafenone and its metabolites in a
case of severe poisoning.
AB - CASE REPORT: Propafenone is a class IC antiarrhythmic agent metabolized into two
major metabolites, 5-hydroxypropafenone and N-depropylpropafenone. The potency of
5-hydroxypropafenone to block fast sodium channels is comparable to that of its
parent. We report the positive correlation between plasma concentrations and
electrocardiographic changes in a patient with severe oral self-poisoning. Serial
ECG changes were measured and plasma concentrations were determined by high
performance liquid chromatography. The initial plasma concentrations of
propafenone were in the toxic range and correlated with the widening of the QRS
complex. The slow decline in concentration during this first phase might relate
to saturation of the isoenzyme CYP2D6. The half-life of propafenone, calculated
from the second phase, was approximately 3 hours, defining the patient as a fast
metabolizer. The initial concentrations of the metabolite N-depropylpropafenone
were surprisingly higher than those of 5-hydroxypropafenone which may also be due
to saturation of CYP2D6.
PMID- 9656984
TI - Acute cerebral gas embolism from hydrogen peroxide ingestion successfully treated
with hyperbaric oxygen.
AB - CASE REPORT: We present a case of an adult who suffered an apparent stroke
shortly after an accidental ingestion of concentrated hydrogen peroxide. Complete
neurologic recovery occurred quickly with hyperbaric therapy. Hydrogen peroxide
can produce acute gas embolism. Hyperbaric therapy is the definitive treatment
for gas embolism from hydrogen peroxide ingestion as it is for all other causes
of acute gas embolism. This is the first case reported in the literature of
hyperbaric therapy used successfully to treat cerebral gas embolism caused by
hydrogen peroxide.
PMID- 9656985
TI - Possible serotonin syndrome from paroxetine and clonazepam.
PMID- 9656986
TI - Getting to the root (Acorus calamus) of the problem.
PMID- 9656987
TI - Liver injury after contrast-enhanced, computed tomography with iopromide.
PMID- 9656988
TI - Regulatory and safety issues regarding special nutritional products.
PMID- 9656989
TI - Nuclear import and export of viruses and virus genomes.
AB - Many viruses replicate in the nucleus of their animal and plant host cells.
Nuclear import, export, and nucleo-cytoplasmic shuttling play a central role in
their replication cycle. Although the trafficking of individual virus proteins
into and out of the nucleus has been well studied for some virus systems, the
nuclear transport of larger entities such as viral genomes and capsids has only
recently become a subject of molecular analysis. In this review, the general
concepts emerging are discussed and a survey is provided of current information
on both plant and animal viruses. Summarizing the main findings in this emerging
field, it is evident that most viruses that enter or exit the nucleus take
advantage of the cell's nuclear import and export machinery. With a few
exceptions, viruses seem to cross the nuclear envelope through the nuclear pore
complexes, making use of cellular nuclear import and export signals, receptors,
and transport factors. In many cases, they capitalize on subtle control systems
such as phosphorylation that regulate traffic of cellular components into and out
of the nucleus. The large size of viral capsids and their composition (they
contain large RNA and DNA molecules for which there are few precedents in normal
nuclear transport) make the processes unique and complicated. Prior capsid
disassembly (or deformation) is required before entry of viral genomes and
accessory proteins can occur through nuclear pores. Capsids of different virus
families display diverse uncoating programs which culminate in genome transfer
through the nuclear pores.
PMID- 9656990
TI - Suppression of antigen-specific T cell proliferation by measles virus infection:
role of a soluble factor in suppression.
AB - Measles virus infection causes a profound immunosuppression. The basis for this
immunosuppression is not known. This immunosuppression could be due to virus
acting directly on lymphoid cells, the production of an immunosuppressive viral
product, or a lymphoid product. We have developed an antigen-specific T cell
system to study measles virus-T-cell interactions. We demonstrate that as few as
five infectious viral particles added to 1000 T cells results in profound
inhibition of antigen-specific T cell proliferation. Supernates taken from
measles virus-infected T cells suppress the proliferation of uninfected T cells.
Measles-virus-infected HeLa or Vero cells do not produce the factor. The
antiproliferative effects of the supernates cannot be attributed to infectious
virus, IL-10 or TGF-beta. The soluble factor appears to be larger than 100 kDa,
yet retains antiproliferative activity following trypsin digestion with a size
less than 10 kDa. Loss of activity is seen following heat treatment at 56 degrees
C. The factor is lymphoid cell specific and exhibits cytokine-like behavior yet
appears not to be a known cytokine. This soluble factor may be responsible for
the overt clinical immunosuppression seen in man and a previously undescribed
cytokine induced by measles virus infection of human lymphocytes.
PMID- 9656991
TI - The 105-kDa polyprotein of southern bean mosaic virus is translated by scanning
ribosomes.
AB - The cowpea strain of southern bean mosaic virus (SBMV-C) is a positive-sense RNA
virus. Three open reading frames (ORF-1, ORF2, and ORF3) are expressed from the
genomic RNA. The ORF1 and ORF2 initiation codons are located at nucleotide (nt)
positions 49 and 570, respectively. ORF1 is expressed by a 5' end-dependent
scanning mechanism, but it is not known how ribosomes gain access to the ORF2
initiation codon. In experiments described here, it was demonstrated that the
translation of ORF2 was sensitive to cap analog in a cell-free extract. In vitro
and in vivo studies showed that the addition of one or more AUG codons between
the 5' end of the SBMV-C RNA and the ORF2 initiation codon reduced ORF2
expression and that elimination of the ORF1 initiation codon increased ORF2
expression. Altering the sequence context of the ORF1 initiation codon to one
more favorable for translation initiation also reduced ORF2 expression in vivo.
Nucleotide deletions and insertions between SBMV-C nt 218-520 did not abolish
ORF2 expression. In most cases, these mutations resulted in reduced expression of
both ORF1 and ORF2. These results are consistent with translation of ORF2 by
leaky scanning.
PMID- 9656992
TI - Nef proteins of distinct HIV-1 or -2 isolates differ in their binding properties
for HCK: isolation of a novel Nef binding factor with characteristics of an
adaptor protein.
AB - The Nef gene of the human and simian immunodeficiency viruses HIV and SIV has
been implicated in pathogenicity; however, the mechanism by which Nef induces
disease is still unknown. An impact on signal transduction in cells has been
suggested by the interaction of Nef from an HIV-1 strain and tyrosine kinases
like HCK and LCK as well as serine/threonine kinases. We have confirmed the
binding of HCK to HIV-1 subtype B Nef and demonstrated an equally strong
interaction with a subtype E Nef protein but weaker binding to Nef of HIV-2
subtype A (HIV-2D194). No binding, however, was observed to HIV-2 subtype B Nef
(HIV-2D205). Instead, this protein bound to a novel cellular protein, Nefin 1,
with characteristics of an adaptor protein and strong expression in all human
hematopoietic tissues. Nefin 1 binds through an amino-terminal domain, which is
related to SH3 domains. For interaction of Nef with Nefin 1, the PxxP motif and
the three-dimensional conformation of the molecule appear necessary. In
conclusion, this study demonstrates that Nef proteins of divergent strains of HIV
1 and HIV-2 may use different elements of signal transduction pathways for the
induction of pathogenicity in vivo.
PMID- 9656993
TI - Shared antigenic epitopes on the V3 loop of HIV-1 gp120 and proteins on activated
human T cells.
AB - Proliferation of HIV-1 in the infected host is characterized by a progressive
loss of CD4+ T lymphocytes and consequent dysregulation of the immune system.
Both direct and indirect mechanisms have been proposed. We show here that
proteins with molecular weights 35, 48, and 110 kDa on stimulated primary human T
cells are recognized by neutralizing antibodies against the V3 loop of HIV-1
gp120. Recognition is specific since it can be blocked by a recombinant HIV-1
gp120. Furthermore, these V3 monoclonal antibodies, as well as sera from AIDS
patients that recognized these V3-like proteins, induced killing of HIV-1
infected as well as uninfected T cells. This killing was also inhibited by HIV-1
gp120 V3 peptides. These results indicate that the V3 loop shares epitopes with
proteins on stimulated T cells. This may be an additional autoimmune mechanism
contributing to CD4+ T cell disappearance in AIDS. V3 antibodies have been
proposed as potential prophylactic agents. However, if such vaccines were based
on certain epitopes, they might induce cross-reacting immune responses with
cellular proteins. Vaccine candidates should be evaluated for such potential
effects.
PMID- 9656994
TI - The structural gene module in Streptococcus thermophilus bacteriophage phi Sfi11
shows a hierarchy of relatedness to Siphoviridae from a wide range of bacterial
hosts.
AB - The structural gene cluster and the lysis module from lytic group II
Streptococcus thermophilus bacteriophage phi Sfi11 was compared to the
corresponding region from other Siphoviridae. The analysis revealed a hierarchy
of relatedness. phi Sfi11 differed from the temperate S. thermophilus
bacteriophage phi O1205 by about 10% at the nucleotide level. The majority of the
changes were point mutations, mainly at the third base position. Only a single
gene (orf 695) differed substantially between the two phages. Over the putative
minor tail and lysis genes, phi Sfi11 and the lytic group 1 S. thermophilus phi
Sfi19 shared regions with variable degrees of similarity. Orf 1291 from phi Sfi19
was replaced by four genes in phi Sfi11, two of which (orf 1000 and orf 695)
showed a complicated pattern of similarity and nonsimilarity compared with phi
Sfi19. The predicted orf 695 gp resembles the receptor-recognizing protein of T
even coliphages in its organization, but not its sequence. No sequence similarity
was detected between phi Sfi11 and phi Sfi19 in the region covering the major
head and tail genes. Comparison of the structural gene map of phi Sfi11 with that
of Siphoviridae from gram-positive and -negative bacterial hosts revealed a
common genomic organization. Sequence similarity was only found between phi Sfi11
and Siphoviridae from gram-positive hosts and correlated with the evolutionary
distance between the bacterial hosts. Our data are compatible with the hypothesis
that the structural gene operon from Siphoviridae of the low G + C group of gram
positive bacteria is derived from a common ancestor.
PMID- 9656995
TI - Proteolytic processing of rubella virus nonstructural proteins.
AB - The genomic RNA of rubella virus contains two long open reading frames (ORF), a
5'-proximal ORF that codes for the nonstructural proteins and a 3'-proximal ORF
that encodes the structural proteins. The cDNA encoding the nonstructural protein
ORF of the wild-type M33 strain of rubella virus has been obtained and sequenced.
Comparison between the nonstructural proteins of the M33 and Therien strains of
rubella virus revealed a 98% homology in nucleotide sequence and 98.1% in deduced
amino acid sequence. To examine the processing of rubella virus nonstructural
protein, the complete nonstructural protein ORF was expressed in BHK cells using
a pSFV expression vector. Three nonstructural protein products (p200, p150, and
p90) with molecular weights of 200, 150, and 90 kDa were identified using
antisera raised against synthetic peptides corresponding to regions of the
nonstructural proteins. p200 is the polyprotein precursor, while p150 and p90 are
the cleavage products. Site-directed mutagenesis of the Cys-1151 residue (one of
the catalytic dyad residues of the viral protease) and of the Gly-1300 residue
(the viral protease cleavage site) abrogated protease activity and p200 precursor
cleavage, respectively. Coexpression of mutant constructs in BHK cells indicated
that rubella virus protease can function both in cis and in trans.
PMID- 9656996
TI - Membrane-anchored incorporation of a foreign protein in recombinant influenza
virions.
AB - The RNA polymerase I system for in vivo synthesis of recombinant influenza vRNA
molecules was used for the expression of a chimeric protein, consisting of the
341-amino-acid ectodomain of the glycoprotein E2 of classical swine fever virus
and the 37-amino-acid C-terminal membrane anchor of the influenza virus
hemagglutinin (HA). During infection with an influenza A helper virus the
amplified pseudo-viral RNA was packaged into progeny virions together with
influenza vRNA segments. The foreign fusion protein E2-HA was shown to be
physically incorporated into the viral envelope. Incorporation of a third major
glycoprotein into the envelope did not affect biological functions of HA and
neuraminidase that are required for the generation of infectious virus particles.
Based on mutational analyses of the cytoplasmic tail of E2-HA fusion proteins
three modes of interaction during virus budding have been observed: nonspecific
low-level incorporation (truncated tails), specific full-level incorporation
(wild-type amino acid sequence or minor variations of it), and exclusion from
incorporation (elongated tails).
PMID- 9656997
TI - The interaction of neuraminidase and hemagglutinin mutations in influenza virus
in resistance to 4-guanidino-Neu5Ac2en.
AB - We have previously described a 4-guanidino-Neu5Ac2en (zanamivir)-resistant
neuraminidase (NA) variant G70C4-G, with an active site mutation Glu 119 to Gly.
This variant has been found to also harbor a hemagglutinin (HA) mutation in the
receptor binding site, Ser 186 to Phe. Examination of early passages of the G70C4
G virus revealed that this HA mutation had arisen by the first passage. From a
subsequent passage two transient variants were isolated which had each acquired a
different second HA mutation, Ser 165 to Asn and Lys 222 to Thr. Both were highly
drug resistant and drug dependent and their ability to adsorb to and penetrate
cells was decreased. Comparison of drug sensitivities between the variant, with
the additional HA mutation at Ser 165, and viruses with either mutation alone
revealed that these two HA mutations acted synergistically to increase
resistance. To determine the contribution to resistance of each of the NA and HA
mutations in G70C4-G, the NA mutation was separated from the HA mutation by
reassorting. The NA mutation and the HA mutation each conferred low-level
resistance to zanamivir, while the two mutations interacted synergistically in
the double mutant to give higher resistance in vitro. Infectivity was not
adversely affected in the double mutant and while there was a small decrease in
sensitivity to zanamivir in the mouse model, there was no detectable resistance
to zanamivir in the ferret model.
PMID- 9656998
TI - Critical point mutations for hepatitis C virus NS3 proteinase.
AB - The hepatitis C virus NS3 proteinase plays an essential role in processing of HCV
nonstructural precursor polyprotein. To detect its processing activity, we
developed a simple trans-cleavage assay. Two recombinant plasmids expressing the
NS3 proteinase region and a chimeric substrate polyprotein containing the NS5A/5B
cleavage site between maltose binding protein and protein A were co-introduced
into Escherichia coli cells. The proteinase processed the substrate at the single
site during their polyprotein expression. Deletion analysis indicated that the
functionally minimal domain of the NS3 proteinase was composed of 146 amino
acids, 1059 to 1204. We isolated several cDNA clones encoding the functional
domain of the NS3 proteinase from the sera of patients chronically infected with
HCV and determined their proteinase activity by this trans-cleavage assay. Both
active and inactive clones existed in the same patients. Comparative sequence
analyses of these clones suggested that certain point mutations seemed to be
related to the loss of proteolytic activity. This was confirmed by back mutation
experiments. Among the critical mutations, Pro-1168 to Thr and Arg-1135 to Gly
were intriguing. These amino acids, which are situated near the oxyanion hole,
seem to be essential for maintaining the conformation of the active center of the
NS3 proteinase.
PMID- 9656999
TI - Primary SIVsm isolates use the CCR5 coreceptor from sooty mangabeys naturally
infected in west Africa: a comparison of coreceptor usage of primary SIVsm, HIV
2, and SIVmac.
AB - Genetically divergent strains of simian immunodeficiency virus (SIV) from
macaques (mac), chimpanzees, and sooty mangabeys (SM) efficiently used rhesus and
human CCR5 (R5), but not CXCR4 (xR4), for cell entry. Thus far, however, no
studies have characterized primary SIVsm strains for their use of coreceptors
derived from their own natural host. Coreceptor usage of two primary, blood
derived SIVsm isolates, SIVsmSL92b and SIVsmFNS from naturally infected sooty
mangabeys, was determined. Primary SIVsm efficiently used SM-CCR5 expressed on
HOS.CD4 and U87.CD4 cells. Sequence polymorphisms in CCR5 found in four sooty
mangabeys did not alter viral entry. Unlike primary rhesus blood-derived R5
tropic SIVmac251, primary SM blood-derived R5-tropic SIVsm was strongly CD4
dependent. The SM-CXCR4 gene was fully functional for xR4-tropic primate
lentiviruses, but was not used by primary SIVsm. Therefore, the lack of xR4
tropism among naturally occurring SIVsm strains was not due to CxCR4 gene defects
in the natural host. SIVmac derived from four macaques with AIDS also did not use
macaque- or SM-derived CXCR4, showing that xR4 tropism did not develop during
progression to disease as for humans infected with HIV-1. Three of four primary
HIV-2 strains used CCR5 from human, sooty mangabey, and macaque. The fourth, HIV
27924A, obtained from a patient with AIDS, was xR4-tropic. Because SIVmac is most
closely related to HIV-2, SIVmac might be expected to rnimic tropisms of HIV-2
infections. However, the correlation between xR4 tropism and AIDS may be a
species-specific phenomenon limited to humans. The R5-tropic primary SIVsm and
HIV-2 strains grew in CCR5-negative human PBMC, consistent with their use of non
CCR5 coreceptors. However, primary SIVsmSL92b did not use non-CCR5 coreceptors
efficiently. The two primary SIVsm isolates replicated poorly in CEMx174 cells,
which do not express CCR5, compared to CCR5-positive PM1 cells. SIVmac grew
equally well in both cell lines. The findings show that SM-chemokine receptors
are fully functional for virus entry and that multicoreceptor tropism is a common
property of primary lentiviruses within the SIVsm/HIV-2 subfamily.
PMID- 9657000
TI - Characterization of Toscana virus-defective interfering particles generated in
vivo.
AB - Toscana (TOS) virus stocks strongly interfering with standard virus replication
were obtained by sequential passages of virus in suckling mouse brain.
Characterization of viral RNAs in these stocks showed the presence of a
heterogeneous population of defective RNA molecules derived from the L genomic
segment, in both nucleocapsid (NC) and messenger RNAs, suggesting that these
molecules could be replicated, assembled, and transcribed. Subgenomic RNAs from
the L segment but not from the S or M segments were found in cells infected with
these stocks. Defective RNA molecules interfered with virus replication and
retained 5' and 3' genomic termini. Nucleotide sequence analysis of some cloned
defective interfering (DI) RNAs revealed they contained one or more internal
deletions reducing their length to 7-13% of the full-length L segment. An
identical sequence motif, of variable length, was found at both terminal sites of
the RNA junction on standard L sequences. This motif was retained only in one
copy in the subgenomic RNA. These results are consistent with the generation of
TOS virus DI particles in vivo and suggest that the defective genomic RNAs could
be generated by polymerase jumping from a sequence to an identical one spatially
closed because of the RNA structure.
PMID- 9657001
TI - DNA vaccines expressing either the GP or NP genes of Ebola virus protect mice
from lethal challenge.
AB - DNA vaccines expressing the envelope glycoprotein (GP) or nucleocapsid protein
(NP) genes of Ebola virus were evaluated in adult, immunocompetent mice. The
vaccines were delivered into the skin by particle bombardment of DNA-coated gold
beads with the Powderject-XR gene gun. Both vaccines elicited antibody responses
as measured by ELISA and elicited cytotoxic T cell responses as measured by
chromium release assays. From one to four vaccinations with 0.5 microgram of the
GP DNA vaccine resulted in a dose-dependent protection from Ebola virus
challenge. Maximal protection (78% survival) was achieved after four
vaccinations. Mice were completely protected with a priming dose of 0.5 microgram
of GP DNA followed by three or four subsequent vaccinations with 1.5 micrograms
of DNA. Partial protection could be observed for at least 9 months after three
immunizations with 0.5 microgram of the GP DNA vaccine. Comparing the GP and NP
vaccines indicated that approximately the same level of protection could be
achieved with either vaccine.
PMID- 9657002
TI - Functional modules important for activated expression of early genes of herpes
simplex virus type 1 are clustered upstream of the TATA box.
AB - Functional analysis of two promoters controlling early herpes simplex virus type
1 (HSV-1) transcripts encoding the UL37 and UL50 (dUTPase) proteins are described
in this report. Transcripts expressed under the control of these promoters were
found to be expressed early regardless of the position of the transcription unit
within the viral genome. Despite this, wt dUTPase mRNA was 6-10 times more
abundant than the UL37 transcript both in wt and recombinant viruses. This same
difference in transcript abundance was seen when a reporter gene (beta
galactosidase) was controlled by the two promoters in recombinant viruses in the
heterologous glycoprotein C (gC) locus. Thus, both the kinetics and relative
abundance of UL50 and UL37 transcripts are a direct function of their respective
promoter regulatory elements. Characterization of mutated UL37 and UL50 promoters
in recombinant viruses showed that the functional modules important for
expression from these promoters are concentrated upstream of the transcription
start site; however the extent and composition of these modules in terms of the
cis-acting elements they contain was different for each. For the UL37 promoter,
both a HiNF-P factor binding site (-53 to -58 bp) and the TATA homology (-22 to
27) were required for any detectable expression, while an Sp1 binding site at
123 augmented this but was not absolutely required. In contrast, the only
functional elements crucial for expression from the UL50 promoter were the TATA
box (-25 to -31) and an Sp1 binding site at -117 bp relative to the cap site.
Despite differences in detail, when the functional architecture of these two
early promoters were compared to the extensively characterized HSV-1 thymidine
kinase (UL23) promoter, class-specific similarities are clearly apparent.
PMID- 9657003
TI - Evolutionary relationships among putative RNA-dependent RNA polymerases encoded
by a mitochondrial virus-like RNA in the Dutch elm disease fungus, Ophiostoma
novo-ulmi, by other viruses and virus-like RNAs and by the Arabidopsis
mitochondrial genome.
AB - The nucleotide sequence (2617 nucleotides) of virus-like double-stranded (ds) RNA
3a in a diseased isolate, Log1/3-8d2 (Ld), of the ascomycete fungus Ophiostoma
novo-ulmi has been determined. One strand of the dsRNA contains an open reading
frame (ORF) with the potential to encode a protein of 718 amino acids, and the
complementary strand contains two smaller ORFs with the potential to encode
proteins of 178 and 182 amino acids, respectively. The large ORF contains 12 UGA
codons which code for tryptophan in ascomycete mitochondria and has a codon bias
typical of mitochondrial genes, consistent with the localization of Ld dsRNAs
within the mitochondria. The amino acid sequence contains motifs characteristic
of RNA-dependent RNA polymerases (RdRps). This putative RdRp was shown to be
related to putative RdRps of mitochondrial dsRNAs of another ascomycete and a
basidiomycete fungus and also to a putative RdRp encoded by the mitochondrial
genome of Arabidopsis thaliana. In multiple sequence alignments, the fungal
mitochondrial dsRNA-encoded RdRp-like proteins formed a cluster, ancestrally
related to the RdRps of the yeast 20S and 23S RNA replicons and of the positive
stranded RNA bacteriophages of the Leviviridae family, but distinct from RdRps of
other families and genera of fungal RNA viruses and related plant and animal RNA
viruses. Northern blot analysis with RNA 3a strand-specific probes indicated that
nucleic acid extracts of Ld contain more single-stranded (positive-stranded) RNA
than dsRNA, consistent with an evolutionary relationship between RNA 3a and
positive-stranded RNA phages.
PMID- 9657004
TI - Transfer RNA mimicry in a new group of positive-strand RNA plant viruses, the
furoviruses: differential aminoacylation between the RNA components of one
genome.
AB - Recent sequencing of the genomes of several furoviruses--fungus-transmitted rod
shaped positive-strand plant viruses--has suggested the presence of tRNA-like
structures (TLSs) at the 3' ends of the genomic RNAs. We show here that the
genomic RNAs of soil-borne wheat mosaic virus (SBWMV), beet soil-borne virus
(BSBV), potato mop-top virus (PMTV), peanut clump virus (PCV), and Indian peanut
clump virus (IPCV) all possess functional TLSs that are capable of high
efficiency valylation. While the SBWMV, BSBV, and PMTV TLSs are similar to those
found in tymoviruses, the PCV and IPCV TLSs harbor an insertion of about 40
nucleotides between the two halves of the TLS. The valylated SBWMV and BSBV RNAs
formed tight complexes with wheat germ EF-1 alpha.GTP (Kd = 2 to 11 nM), whereas
valylated PMTV, PCV, and IPCV RNAs bound EF-1 alpha.GTP weakly (Kd > or = 50 nM).
The TLS of PCV RNA2 differs from PCV RNA1 in lacking the major valine identity
nucleotide in the anticodon and consequently is capable of only very inefficient
valylation. This is the first case of differential aminoacylation between the RNA
components of one genome.
PMID- 9657005
TI - A cell surface protein with herpesvirus entry activity (HveB) confers
susceptibility to infection by mutants of herpes simplex virus type 1, herpes
simplex virus type 2, and pseudorabies virus.
AB - Certain mutant strains of herpes simplex virus type 1 (HSV-1) are unable to
infect cells in which entry is dependent on HVEM, the previously described
herpesvirus entry mediator designated here as herpesvirus entry protein A (HveA).
These mutant viruses can infect other cells where entry is apparently dependent
on other co-receptors. The mutant virus HSV-1(KOS)Rid1 was used to screen a human
cDNA expression library for ability of transfected plasmids to convert resistant
Chinese hamster ovary cells to susceptibility to virus entry. A plasmid
expressing the previously described poliovirus receptor-related protein 2 (Prr2)
was isolated on the basis of this activity. This protein, designated here as
HveB, was shown to mediate the entry of three mutant HSV-1 strains that cannot
use HVEM as co-receptor, but not wild-type HSV-1 strains. HveB also mediated the
entry of HSV-2 and pseudorabies virus but not bovine herpesvirus type 1. HveB was
expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes,
and primary activated T lymphocytes. Antibodies specific for HveB blocked
infection of HveB-expressing CHO cells and a human fibroblastic cell strain
HEL299. Differences in ability of HSV-1 and HSV-2 strains to use HveB for entry
should influence the types of cells that can be infected and thereby account in
part for serotype and strain differences in tissue tropism and pathogenicity.
PMID- 9657006
TI - Nucleotide sequence of Bombyx mori cytoplasmic polyhedrosis virus segment 8.
AB - The segments 8 (S8) of the 10 double-stranded RNA genomes from Bombyx mori
cytoplasmic polyhedrosis virus (BmCPV) strains I and H were converted into cDNAs,
amplified by PCR, and cloned. The nucleotide sequence analysis of the two full
length S8 cDNAs showed that the segments consist of 1328 nucleotides encoding
putative proteins (p44) of 390 amino acids with molecular masses of about 44 kDa,
which have glutamic acid-rich and proline-rich domains in their central regions.
They had quite high identity with each other: about 98% in nucleotide and amino
acid sequences. The recombinant p44 expressed in BmN4 cells using the baculovirus
vector was detected by immunoblot analysis. p44 was also confirmed with the same
antiserum to be present in BmCPV-infected midgut cells, but not in polyhedra,
virus virions and uninfected midgut cells, indicating that p44 is expressed as a
nonstructural protein of BmCPV.
PMID- 9657007
TI - Genetic alterations in early stage adenocarcinoma of the lung.
PMID- 9657008
TI - Analysis of loss of heterozygosity in small adenocarcinomas of the lung.
AB - BACKGROUND: Despite the many studies of genetic alterations in advanced lung
carcinomas, few reports have analyzed early stage adenocarcinoma of the lung.
METHODS: We focused on small pulmonary adenocarcinomas, classified according to
recently proposed histological criteria (Noguchi M., et al. Cancer 1995;75:2844
52) which divided adenocarcinomas 2 cm or less in diameter into two groups; one
showing replacing growth of the pulmonary alveolar structure [A, localized
bronchioloalveolar carcinoma (LBAC); B, LBAC with alveolar collapse; C, LBAC with
active fibroblastic proliferation] and the other showing non-replacing growth (D,
poorly differentiated adenocarcinoma). Ninety-four small pulmonary
adenocarcinomas, including 40 of type A and B, 30 of type C and 24 of type D,
were examined for loss of heterozygosity (LOH) using microsatellite markers.
RESULTS: The frequencies of LOH were 19.8% in types A and B, 26.8% in type C and
32.7% in type D tumors. There were no significant differences in the frequency of
LOH on chromosomes 2p, 3p, 9p and 17q among tumor types. However, on 17p, the
frequency of LOH was significantly lower for types A and B than for type C or D.
Three out of six type C tumors which were positive for LOH at several loci showed
different LOH patterns in two areas (central and peripheral regions).
CONCLUSIONS: Allelic losses were detected in very early adenocarcinomas and the
frequency of LOHs on chromosome 17p increased during malignant progression of the
tumor. Heterogeneous genetic alterations were demonstrated even in small
pulmonary adenocarcinomas.
PMID- 9657009
TI - Diagnosis and treatment of malignant lymphoma of the parotid gland.
AB - BACKGROUND: To correlate the imaging and pathological features and to discuss
therapeutic modalities and the prognosis of malignant lymphoma originating in the
parotid gland, which is relatively rare. METHODS: The subjects were five patients
with malignant lymphoma originating in the parotid gland. Three and two patients
were stage I and stage II, respectively. CT examination was applied to all,
whereas only one case was examined by MRI. All were treated with radiotherapy
following surgery or chemotherapy. Three patients underwent combination
chemotherapy, such as with MACOP-P or VEPA, following surgery. RESULTS: Although
malignant lymphoma originating in the parotid gland is histologically described
as low-grade non-Hodgkin's lymphoma, two and one of the cases were classified as
intermediate and high grade in the present series, respectively. These three
exhibited a tendency for infiltration into the adjacent tissue and tumor
inhomogeneity in the imaging findings, suggesting a correlation with
histologically intermediate or high-grade non-Hodgkin's lymphoma. It was
successfully controlled by radiotherapy, with dosages ranging from 40 to 44 Gy.
The patients were followed for 2-8 years. No relapse was found in the three
patients with stage I. However, both stage II patients had relapses and were
subjected to additional radiotherapy combined with chemotherapy. Since then, no
tumor relapse has been noted at either this or other sites. CONCLUSIONS:
Malignant lymphoma including intermediate or high grade originating in the
parotid gland indicated satisfactory prognosis following radiotherapy and
chemotherapy.
PMID- 9657010
TI - Cyclophosphamide, adriamycin, 5-fluorouracil and high-dose toremifene for
patients with advanced/recurrent breast cancer. The Japan Toremifene Cooperative
Study Group.
AB - BACKGROUND: Multi-combination chemotherapy consisting of anthracyclines has been
effective but has not invariably prolonged the survival period in
advanced/recurrent breast cancer. The possibility has been discussed that
chemoendocrine therapy combined with endocrine agents is more effective. METHODS:
In order to evaluate the toxicity and efficacy of a new endocrine therapy for
advanced/recurrent breast cancer, we ran a pilot study during the period from
July 1994 to July 1996. RESULTS: Twenty-two patients with advanced/recurrent
breast cancer were treated with chemoendocrine therapy consisting of
cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m2)
i.v. and 5-fluorouracil (500 mg/body) i.v. on day 1 (repeated every 3 weeks for 9
weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20
evaluable patients, two showed complete response (10%), eight partial response
(40%), six no change (30%) and four progressive disease (20%). The overall
response rate was 50%, and the median duration of response was 69.5 days (28-133+
days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity
and hematological toxicity, but these were clinically well tolerated. No serious
cardiac, liver or renal symptom was seen. CONCLUSIONS: Based on these results, we
consider the addition of high-dose toremifene to the CAF therapy to be useful in
the treatment of advanced and recurrent breast cancer.
PMID- 9657011
TI - Nonfunctioning islet cell tumors of the pancreas: clinical, imaging and
pathological aspects in 16 patients.
AB - BACKGROUND: Nonfunctioning islet cell tumors (NFICTs) usually reach a large size
prior to detection, at which stage patients have some symptoms or signs.
Recently, NFICTs have been discovered in asymptomatic patients with increasing
frequency owing to advances in diagnostic imaging techniques. This study
investigated clinical, imaging and pathological features in recent cases of
NFICT. METHODS: The medical records, radiographs and pathological specimens of 16
patients with NFICT who were evaluated between April 1991 and March 1996 were
reviewed. RESULTS: Tumor sizes ranged from 0.8 to 17 cm (average, 5.2 cm). Five
patients (31%) had some symptoms or signs at the time of diagnosis; however, the
other 11 (69%) had no symptoms. Of 10 patients with a tumor of size 5 cm or less,
nine were asymptomatic and all tumors were histologically benign. In contrast, in
six patients with a tumor larger than 5 cm, four had some symptoms and five
tumors were malignant. The detection rates of pancreatic tumor mass on
ultrasonography and computed tomography were 94% (15/16) each. All 14 patients in
whom the tumor was completely resected survived without recurrence; however, the
remaining two patients with liver metastases died following recurrence.
CONCLUSIONS: US and CT are useful in detecting NFICTs even if the tumor is small
and the patient is asymptomatic. The detection of NFICTs of small size and their
complete removal are essential for a successful cure.
PMID- 9657012
TI - Adjunctive value of cell proliferation but not of apoptosis to interpret
pathologic effects on prostatic cancer after neoadjuvant endocrine therapy.
AB - BACKGROUND: The current histological evaluation of the effects of endocrine
therapy has difficulty in distinguishing pathologic degeneration caused by
androgen ablation from residual poorly differentiated tumor. Therefore, we
examined the changes in cell proliferation and apoptosis before and after
endocrine therapy and analyzed whether they correlated with pathologic effects
and histological differentiation. METHODS: Between January 1986 and December
1995, 52 patients with clinical stage B2 and C prostate cancer underwent radical
prostatectomy after neoadjuvant endocrine therapy (median duration 3.8 months).
Proliferative and apoptotic activities of pretreatment biopsy specimens and
radical prostatectomy specimens were analyzed with MIB-1 monoclonal antibody and
in situ end-labeling of fragmented DNA. RESULTS: The mean proliferative index
(PI) of radical prostatectomy specimens was significantly lower than that of
biopsy specimens (P = 0.000003) and the decrease in PI after endocrine therapy
was significantly related to histological differentiation (P = 0.014). There was
a weak relationship between the decrease in PI after endocrine therapy and
pathologic effects (P = 0.054), while in pathologically effective cases (Grades 2
and 3), three out of 16 (19%) showed a < 50% decrease in PI after endocrine
therapy, and may be regarded as having poorly differentiated tumors. The mean
apoptotic index (AI) of prostatectomy specimens tended to be higher than that of
biopsy specimens (P = 0.054). The increase in AI after endocrine therapy was not
related to histological differentiation and pathologic effects. CONCLUSION:
Pathologic effects caused by endocrine therapy may be in part misled by routine
histopathologic staining and the change in PI may help in recognizing the
pathologic effects of endocrine therapy and have adjunctive value for the
interpretation of the effects of endocrine therapy.
PMID- 9657013
TI - Splenic irradiation for prolymphocytic leukemia: is it preferable as an initial
treatment or not?
AB - We describe a case of B-cell prolymphocytic leukemia (PLL) successfully treated
with splenic irradiation (SI). A 69-year-old woman was admitted to our hospital
because of massive splenomegaly and leukocytosis. Peripheral blood showed
hemoglobin (Hb) 7.4 g/dl, platelets 48 x 10(9)/l and white blood cells (WBC) 50.3
x 10(9)/l with 90% prolymphocytes. Bone marrow was hypercellular with 60%
prolymphocytes. Surface marker analysis revealed that prolymphocytes were
positive for CD20, CD22, FMC7, HLA-DR and surface immunoglobulin (mu, delta and
lambda), but negative for CD5 and mouse erythrocyte rosette. A diagnosis of B
cell PLL was made. SI (1.5 Gy x 4/week, total dose 19.5 Gy) was chosen for the
treatment and a remarkable response was achieved immediately after the first
irradiation. Finally, a single course of SI induced complete remission without
any significant side effect. One year after the SI, she showed no splenomegaly
and almost normal peripheral blood cell count (Hb 11.2 g/dl, platelets 100 x
10(9)/l, WBC 3.6 x 10(9)/l with 71% neutrophils and no prolymphocyte). She has
been well for more than 24 months. This case showed that SI may remain valuable
for an initial course of PLL treatment.
PMID- 9657014
TI - Successful treatment by radiation and hormone therapy of isolated local
recurrence of breast cancer 24 years after mastectomy accompanied by immune
thrombocytopenia: a case report.
AB - We report a case of isolated local recurrence of breast cancer, which was
accompanied by idiopathic thrombocytopenic purpura (ITP) and benign monoclonal
gammopathy that presented 24 years after the patient underwent mastectomy. A 72
year-old female patient with a chest wall tumor was referred to our hospital in
November 1994. Twenty-four years previously she had surgically treated breast
cancer, of which the pathology was scirrhous carcinoma. Needle biopsy of the
tumor revealed tubular carcinoma, which is compatible with local recurrence of
breast cancer. She had no evidence of regional lymph node involvement or distant
metastasis. Hematological and serological examination revealed a low platelet
count accompanied by M-proteinemia (IgG, kappa-type) and a mild increase in
platelet-associated IgG. She was initially treated with extensive-field chest
wall radiation (60 Gy), followed by systemic administration of tamoxifen.
Complete local control of isolated local recurrence (LR) was achieved after
radiation therapy (RT) and the patient has been progression-free for more than 2
years. Platelet count recovered gradually to a normal level after achievement of
complete remission induced by radiation and tamoxifen. This may be the first case
suggestive of a paraneoplastic syndrome of immune thrombocytopenia accompanied by
local recurrence of breast cancer.
PMID- 9657015
TI - Malignant phyllodes tumor of the breast with hypoglycemia: report of a case.
AB - A surgically resected case of giant malignant phyllodes tumor of the breast
associated with a hypoglycemic attack is reported. A 54-year-old woman was
referred to our hospital with loss of consciousness and a huge chest wall tumor.
She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and
underwent palliative simple mastectomy because lung metastasis was detected on
computed tomography and by other imaging modalities on admission. The
preoperative laboratory data revealed a very low fasting blood sugar level of 37
mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90
100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly
decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and
the majority of atypical cells stained positively for IGF-II
immunohistochemically. These findings suggested that the patient's hypoglycemia
was associated with IGF-II produced by a giant malignant phyllodes tumor that
consumed glucose.
PMID- 9657016
TI - Spontaneous regression of primary mediastinal germ cell tumor.
AB - A case of primary mediastinal germ cell tumor, which demonstrated spontaneous
regression, is presented. The serum human chorionic gonadotropin level was
elevated on admission and then decreased to the normal range with decrease in the
size of the anterior mediastinal mass. Thoracotomy was performed with artificial
replacement by grafts between the bilateral brachiocephalic veins and the right
atrium. Histological diagnosis of combined teratoma with seminoma was made. After
subsequent chemotherapy, the patient has remained alive without recurrence for
over 10 years.
PMID- 9657017
TI - Primary liposarcoma of the stomach: a case report and a review of the literature.
AB - Primary liposarcoma of the stomach is rare and only seven cases have been
described in the English literature. Here we report the eighth case, which
occurred in a 68-year-old woman who presented with repeated tarry stools and
hematemesis. Endoscopic examination revealed a large ulcerated submucosal mass at
the gastric angle. The patient was treated by total gastrectomy. On microscopic
examination, the tumor showed the features of a well differentiated sclerosing
liposarcoma. Immunohistochemically, many spindle to stellate tumor cells were
diffusely positive for vimentin and CD34. Positivity for S-100 protein was found
in the adipocytic component, including lipoblasts, in addition to some spindle
shaped tumor cells. On ultrastructural examination, the spindle to stellate cells
had features characteristic of fibroblasts. No recurrence or metastasis was seen
during 13 months. Liposarcoma of the stomach has to be considered in the
differential diagnosis with other submucosal lesions, such as gastric lipoma and
gastrointestinal stromal tumor.
PMID- 9657019
TI - [Postanesthesia allergic complications].
PMID- 9657018
TI - Hereditary nonpolyposis colorectal cancer associated with duodenal carcinoma: a
case report.
AB - Hereditary nonpolyposis colorectal cancer is an autosomal, dominantly inherited
disease, characterized by an early age of onset, right colon predominance and an
association with various extracolorectal malignancies. We present a case of a 47
year-old woman who met the clinical criteria for the diagnosis of hereditary
nonpolyposis colorectal cancer from her past and family histories. She had
undergone operations for uterine cancer (histology not confirmed) at age 35 and
for advanced cancer of the ascending colon at age 45. Gastroendoscopy revealed a
flat elevated lesion, 20 mm in size, with a protrusion (type IIa + Is) in the
second portion of the duodenum in March 1996. Additionally, colonoscopy showed a
flat elevated lesion, 30 mm in size, with an irregular and nodular surface (type
IIa, laterally spreading tumor) in the descending colon. After the operation, the
resected specimen of the duodenum histologically showed a well-differentiated
adenocarcinoma associated with a tubulo-villous adenoma which had invaded the
submucosal layer. The tumor of the colon was histologically confirmed to be a
moderately-differentiated adenocarcinoma with submucosal invasion. A high
frequency of replication error positivity (4/5 loci) was detected in both of the
tumors. Reports of early cancer of the duodenum, associated with extracolorectal
malignancies in hereditary nonpolyposis colorectal cancer, are very rare in the
literature. Although it is difficult to determine which extracolorectal tumor
sites should be taken into consideration by screening programs, we believe that
careful observation by upper gastrointestinal endoscopy, which includes the
duodenum, is necessary for patients with hereditary nonpolyposis colorectal
cancer.
PMID- 9657020
TI - [The beginning of anesthesia].
AB - On October 16, 1846, the first public demonstration of etherization, at the
Massachusetts General Hospital, Boston, illustrated the rise of Inhalational
Anaesthesia. Pioneers were: Hickman, Wells, Morton, Davy and Long. Anaesthesia
was considered an American invention. Thereafter, the development of new
molecules (cocaine, hexobarbital) which can be administered by others ways
(spinal puncture, intravenous injections) allowed new methods of anaesthesia to
be achieved. Thus, three successive periods have illustrated the Story of
Anaesthesia: Inhalational Anaesthesia (1844), Local Anaesthesia (1860),
Intravenous Anaesthesia (1932).
PMID- 9657021
TI - [Mechanism of severe, immediate reactions to iodinated contrast material].
AB - Immediate reactions to iodinated contrast material are usually supposed to be due
to complement activation. Histamine has not been proved responsible for signs.
However the results described in the literature are controversial: they have been
obtained from non-reacting patients or during minor or moderate reactions. We
suggest to study mediator release during unexpected severe reactions and to
perform skin tests and IgE measurements in patients with proved liberation of
mediators.
PMID- 9657022
TI - [Postoperative allergic complications: the role of the anesthetist in conducting
the immuno-allergic investigation].
AB - When peri-anaesthesia anaphylactic and/or anaphylactoid reactions occur,
anaesthetist is the first investigator: the quality of immuno-allergological
investigations depends on these initial investigational procedures. We have used
sample kits for several years in order to make easier the immediate
investigation. From retrospective analysis of the allergic complications which
happened in 1997, the importance of these sample kits as well as the
anaesthetist's part in the immuno-allergological management are examined. Nine
observations were itemized (0.047%): 3 generalized erythema observations (grade
I), in which atracurium was incriminated twice, and propacetamol once; 2
observations of grade II, in which vecuronium (elevated tryptase) and atracurium
were incriminated; 4 anaphylactic shocks, in which three neuromuscular blocking
drugs (suxamethonium, vecuronium and pancuronium), and one antibiotic
(cloxacilline) were incriminated. The use of sample kits allowed an early
diagnosis approach, confirmed by skin tests. Diagnosis should be thought closely
between anaesthetists and immunologists for investigations.
PMID- 9657023
TI - [Propacetamol and new occupational contact dermatitis].
AB - We describe the cases of three hospital nurses who presented eczematous lesions
on the hands and eyelids. They worked in surgery department or in post
anaesthesia recovery room, all preparing syringes of Pro-Dafalgan (propacetamol:
parenteral paracetamol form). They were not sensitive to oral paracetamol or
occupational products and latex. During week-end or holidays when they stopped
handling Pro-Dafalgan, the eczema recovered but relapsed on working. A few cases
are described in the literature so precautions begin to be preconized for
healthcare workers but they are not usually in practice. Test performed with
solvent, paracetamol, latex, formol and other hospital allergen tests were
negative. The only allergen would be propacetamol because all tests performed
with it were strongly positive. Following the official evaluation method in
pharmacovigilance, based on chronologic and semiologic criterias, considering the
positivity of rechallenge and specific tests, propacetamol imputability was
probable in all our cases. It is preconized to declare cases to Regional
Pharmacovigilance Centers to complete information about handling risks of this
very usual analgesic.
PMID- 9657024
TI - Nasal allergen challenge and immunotherapy control.
AB - Nasal allergen challenges, despite not reproducing exactly natural allergen
exposure, are a very useful method to understand the complex cellular kinetics
and cellular interactions that occur in allergic rhinitis. Cell-specific soluble
mediator measurements can give useful diagnosis information as well as
complementary information regarding the monitoring of specific immunotherapy. In
this article we present data concerning eosinophil cationic protein and tryptase
measurements after nasal allergen and the influence of specific immunotherapy on
nasal peak flow before and 1, 2 and 3 years after starting immunotherapy.
PMID- 9657025
TI - [Systemic contact dermatitis].
AB - The field of systemic contact dermatitis is particularly interesting for an
allergist. To think of an allergen with cross-reaction and monosensilization
should be the first reflex when an enquiry into a skin problem involves an
allergic symptom. The three examples quoted involve Peruvian balm as the
sensitizing agent. The causal triggering medicines are all vegetal extracts.
PMID- 9657026
TI - [Cancer of the kidney in adults. Apropos of 60 cases].
AB - The authors report a series of 60 cases of renal cancer observed over a 10-year
period. Patients consisted of 35 women (58%) and 25 men (42%), with a mean age of
52 years (range: 21-72 years). The clinical features were polymorphic, dominated
by loin pain (76%), haematuria (75%), a lumbar mass (46%), alteration of the
general state (30%). The diagnosis was established by ultrasonography in 58
patients and CT scan in 38 patients. The mean tumour diameter was 11.5 cm (5-25
cm) and two cases presented bilateral tumours. The tumour was located in the
upper pole in 40% of cases and was mid-renal in 30% of cases. The time to
diagnosis ranged from 2 months to 3 years. Staging reflected the advanced stage
of the cancer. Treatment was surgical for 53 patients (88%). A lumbar incision
was generally performed (83%). The surgical procedure consisted of nephrectomy
and regional or hilar lymph node dissection. Nephrectomy was simple for 27% of
patients, radical for 69% of patients and partial for 4% of patients. The
postoperative course was marked by one death due to pulmonary embolism, and a
stercoral fistula in 2 patients. Histological examination of the specimen showed
clear cell adenocarcinoma in 92% of cases. The tumour weight was often
considerable, with a maximum of 3.750 kg. The lymph nodes removed were invaded in
50% of cases. The mean follow-up was 46 months (12 to 120 months). Follow-up was
normal at 3 years for 23 patients (43%) and at 10 years for 4 patients (8%).
Tumour recurrence in the renal compartment was observed in 3 patients after 3
years. Asynchronous metastases occurred in 10 patients (23%). The mean interval
to metastases was 20 months (4 to 36 months).
PMID- 9657027
TI - [Renal angiomyolipoma. Apropos of 11 cases].
AB - The authors report their experience of 11 cases of renal angiomyolipoma over an
interval of 20 years, observed in 10 women (90.9%) and one man (9.1%) with a mean
age of 46 years (range: 21 to 63). Clinical symptoms were dominated by loin pain
(100%), haematuria (45.4%), lumbar mass (72.7%), fever (18%). In one woman, AML
was associated with "tuberous sclerosis". Preoperatively, the diagnosis was
established by ultrasound and CT scan in 45.4% of patients. The size of the
tumour varied from 7 to 14 cm in 10 patients and in one patient was only about
3.6 cm. Two women had bilateral tumours. Treatment consisted of total nephrectomy
in 7 patients, partial nephrectomy in 3 patients and tumourectomy in one patient.
The purpose of this study is to analyse the epidemiologic, diagnostic and
therapeutic aspects of this disease.
PMID- 9657028
TI - [Discovery of a renal chromophobe cell carcinoma in a pregnant woman. Apropos of
a case].
AB - We report the case of a young pregnant woman with a malignant tumour of the
kidney suggestive of oncocytoma. Because of the pregnancy, preoperative staging
consisted of abdominal ultrasound and magnetic resonance imaging. Caesarean
section was performed. Several days later, surgical exploration of the kidney was
performed with tumourectomy and frozen section analysis: radical nephrectomy was
finally performed. The definitive histology was chromophobe renal cell carcinoma.
This is a rare tumour of the kidney, with its own characteristics allowing
histopathological diagnosis and with a better prognosis than renal cell
carcinoma. In the literature, pregnancy, a situation of immune depression, does
not increase the prevalence of malignant neoplasms.
PMID- 9657029
TI - [A triple association: renal malacoplakia, bilateral vulvar hypertrophy, upper
limb algodystrophy].
AB - The authors report a case of malakoplakia of the left renal parenchyma, an
uncommon site for an inflammatory disease first described in the bladder by
Michaelis and Guttmann in 1902 and Von Hansmann in 1903. This case was observed
in a 24-year-old girl with no urological history, presenting with bilateral
vulval hypertrophy and reflex sympathetic dystrophy of the upper limbs, in whom
malakoplakia of the left kidney was discovered incidentally. Intravenous
urography showed two large kidneys with a stretched appearance of the renal
pelvis. Pathological examination of the partial nephrectomy specimen revealed the
diagnosis of malakoplakia, an inflammatory diseases of the renal parenchyma. The
pathogenesis has been only partially elucidated, but probably involves a disorder
of macrophage function.
PMID- 9657030
TI - [Laparoscopic adrenalectomy. A general review of a current technic].
AB - The anatomical situation of the adrenal gland explains the diversity of the
surgical incisions used for adrenalectomy. Laparoscopic adrenalectomy was first
performed in 1992. It allows eradication of small adrenal lesions, which are
often incidental findings. There are two routes of laparoscopic access to the
adrenal gland: transperitoneal and retroperitoneal. Laparoscopy allows excellent
operative exposure, reduction of postoperative pain and hospital stay and rapid
convalescence. Retroperitoneoscopy, by allowing direct access to the
retroperitoneum, is more rapid than the transperitoneal route.
PMID- 9657031
TI - [Percutaneous endopyelotomy. Apropos of 27 cases].
AB - 27 percutaneous endopyelotomies were performed in 27 patients from February 1989
to January 1996 to treat 20 cases of congenital hydronephrosis and 7 cases of
acquired stenosis. Strictures of uretero-pelvic junction were treated by
electrocautery with postoperative drainage using a double J stent in 11 cases, or
Redon drain in 16 cases. The evaluable results for 25 patients with a mean follow
up of 11 months showed an overall success rate of 80%. This technique is the
treatment of choice for acquired stenosis and stage I and II congenital
hydronephrosis (Cendron).
PMID- 9657032
TI - Aetiopathogenesis and treatment of idiopathic retroperitoneal fibrosis.
AB - Idiopathic retroperitoneal fibrosis (IRF) is a rare urological disease, for which
many pathogenic theories have been proposed. The authors report a series of 13
cases of IRF in order to evaluate the clinical, diagnostic, laboratory,
therapeutic and prognostic aspects. They also report a rare case (the ninth case
reported in the literature) of multifocal fibrosclerosis. A possible genetic
predisposition was studied by testing for the presence of immunophenotype HLA
B27; this test was positive in 44% of cases. A study of the immunological profile
and lymphocyte populations revealed the typical features of chronic immune
disease. Experience with medical and surgical treatment is reported, comparing
various procedures: ureterolysis followed by application of a vascularized
omental flap over the ureter (without subsequent corticosteroid therapy) gave the
best results, with complete resolution of the symptoms and long-term successful
alleviation of ureteric obstruction in 100% of patients, with a mean follow-up of
58 months.
PMID- 9657033
TI - [Vestigial retrorectal dermoid cyst. Apropos of a case].
AB - A case of recto-rectal congenital development cyst is described in 35-year-old
man. This cyst presented in the form of voiding symptoms. Computed tomography
revealed the relation and components of the development cyst. Treatment consisted
of complete surgical excision via a transabdominal approach.
PMID- 9657034
TI - [Tumors of the bladder in women. Epidemiologic and therapeutic aspects. Apropos
of 40 cases].
AB - Bladder tumours in women. Epidemiological aspects and treatments, based on a
series of 48 cases. Bladder tumours are more frequent in men than in women, in
whom they present certain epidemiological, clinical and therapeutic
characteristics. The authors report a retrospective study of 48 cases of bladder
tumour in women, observed in the urology department over a 20-year period. These
tumours represented 4.2% of all bladder tumours. The patients had a mean age of
59 years (range: 29 to 77). Only one patient was a smoker (2%). Haematuria was
present in 93% of cases, and signs of bladder irritation were present in 60% of
cases. All tumours were transitional cell carcinomas. The tumour was classified
as stage 0 in 10 cases (20.9%), stage A in 15 patients (31.2%), stage B in 22
patients (45.8%) and stage C in 1 case (2.1%); no patients (0%) were classified
as stage D. Our therapeutic protocol was established as a function of the stage
of tumour invasion. For example, superficial tumours were treated conservatively
by transurethral resection, either alone or combined with intravesical
instillation. Radical surgery was performed whenever possible for invasive
tumours. External urinary diversion was performed in 11 cases,
ureterosigmoidostomy in 3 cases and enterocystoplasty in 5 cases. The clinical
course of the 15 superficial tumours was marked by recurrence in 5 cases, while
that of the 23 invasive tumours was marked by local recurrence (3 cases), renal
failure (1 case) and 3 deaths.
PMID- 9657035
TI - [Paratesticular malignant mesothelioma. Presentation of a case].
AB - We report a case of malignant mesothelioma of tunica vaginalis in a 65-year-old
man. The clinical course was marked by local relapse and distant metastases.
Based on a review of the literature, the authors discuss the clinical,
epidemiological and therapeutic aspects.
PMID- 9657036
TI - Basic studies on N''-ursodeoxycholyldiethylenetriamine-N,N,N'-triacetic acid for
the dissolution of calcified gallstones.
AB - A novel calcium-chelating agent, N"-ursodeoxycholyldiethylenetriamine-N,N,N'
triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve
calcified gallstones. The chelating activity of the compound was demonstrated by
dissolving calcium carbonate in vitro at a high dissolution rate. In the presence
of the agent, sliced human gallstone with a composition of more than 50% calcium
bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was
dissolved from the gallstone. The ability to dissolve calcium was comparable to
that of EDTA. However, the laminar structure of the sliced gallstone did not
disappear in the presence of EDTA, whereas the structure disappeared in the
presence of UDCA-DTTA. All these results indicate that UDCA-DTTA is an
interesting compound as a parent substance for developing a prodrug for an oral
or intravenous agent to dissolve calcium-containing gallstones.
PMID- 9657037
TI - Effect of replacing a high linoleate oil with a low linoleate, high alpha
linolenate oil, as compared with supplementing EPA or DHA, on reducing lipid
mediator production in rat polymorphonuclear leukocytes.
AB - The fatty acid composition of rat polymorphonuclear leukocytes (PMN) was modified
by diets supplemented with a high linoleate (LA) safflower oil (76% LA), mixtures
of eicosapentaenoate (EPA) and safflower oil (EPA(20) containing 20% EPA and 61%
LA, EPA(40) containing 40% EPA and 46% LA), mixtures of docosahexaenoate (DHA)
and safflower oil (DHA(20) containing 20% DHA and 61% LA, DHA(40) containing 40%
DHA and 46% LA) or a high alpha-linolenate (alpha-LNA) perilla oil (57% alpha-LNA
and 13% LA), and then lipid mediator production in casein-induced peritoneal PMN
were compared. EPA and DHA were relatively ineffective in reducing platelet
activating factor (PAF) production; a statistically significant reduction was
observed only in the DHA(40) group. In contrast, perilla oil reduced PAF
production by 50% as compared with safflower oil. Arachidonate (AA) in the PAF
precursor, 1-alkyl-2-acyl-glycerophosphocholine, was roughly correlated with PAF
production, but EPA and DHA in the precursor lipid were relatively unrelated. On
the other hand, both PGE2 and LTB4 production correlated positively with AA and
negatively with EPA and DHA in PMN phospholipids; EPA tended to be somewhat more
effective than DHA in reducing PGE2 and LTB4 formation; the activity of perilla
oil was no less than EPA(20). Thus, replacing safflower oil with perilla oil was
no less effective than supplementing safflower oil with EPA or DHA (at 40% of
total fatty acids) in reducing lipid mediator production in rat PMN.
PMID- 9657038
TI - Determining specific gravity, specific heat, and surface area of rabbits for a
possible thermodynamic approach to body temperature change.
AB - In order to investigate the mechanisms of body temperature change from a
thermodynamic aspect, we investigated the specific gravity, specific heat and
surface area of rabbit in situ. We obtained the following results. 1. The
specific gravity of normal, shorn and ecdysed rabbits is 0.94, 0.95 and 0.97,
respectively. 2. The specific heat of normal, shorn and ecdysed rabbits is 0.95,
0.89 and 0.69 cal/g.K, [corrected] respectively. 3. The surface area of the
rabbit was also measured by using the weight of aluminum foil which covered the
surface.
PMID- 9657039
TI - Mechanisms for 5-fluorouracil resistance in human colon cancer DLD-1 cells.
AB - A 5-fluorouracil (5-FU)-resistant subline, DLD-1/5-FU, was established by
repeated 5-d exposures of human colon cancer DLD-1 cells to 5-FU. DLD-1/5-FU
cells were 41- and more than 75-fold resistant to 96-h and 1-h exposures to 5-FU,
respectively. When exposed to 5-FU, DLD-1/5-FU cells exhibited marked resistance
to in situ thymidylate synthase (TS) inhibition by 5-FU as compared to DLD-1
cells, and incorporation of 5-FU into cellular RNA in DLD-1/5-FU cells decreased
to 25% of that in DLD-1 cells. As causes of resistance to DNA and RNA-directed
actions of 5-FU, remarkable reduction of intracellular levels of both 5
fluorouridine 5'-triphosphate (FUTP) and 5-fluoro-2'-deoxyuridine 5'
monophosphate (FdUMP) in DLD-1/5-FU cells was confirmed. It was found that
activities of uridine kinase, orotate phosphoribosyltransferase and thymidine
kinase of DLD-1/5-FU cells were significantly lower than those of the parent
cells. Intracellular levels of TS were similar between the two cell lines. These
results indicated that the mechanism of resistance to 5-FU in DLD-1/5-FU cells
involves reduced enzymatic activation of 5-FU.
PMID- 9657040
TI - Separation of phospholipase A2 in Habu snake venom by glycyrrhizin (GL)-affinity
column chromatography and identification of a GL-sensitive enzyme.
AB - By means of glycyrrhizin (GL)-affinity and Mono S column chromatographies (HPLC),
at least four GL-binding proteins (p25, p17, p15-1 and p15-2) in the two Superdex
fractions (P-II and P-III fractions) from Habu snake venom were selectively
purified. By determination of their N-terminal partial amino acid sequences, a
metalloprotease (p25) and three GL-binding phospholipases A2 (gbPLA2s) [PA2Y
(p17), PA21 (p15-1) and PA2B (p15-2)] were identified. PA2B (lysine-49 PLA2) was
found to be the most sensitive to GL because (i) it strongly bound to a GL
affinity column; and (ii) its enzyme activity was selectively inhibited by low
dose (ID50 = approx. 1.5 microM) of GL, but not by GA. Furthermore, these three
gbPLA2s were phosphorylated by casein kinase II (CK-II) in vitro and GL inhibited
the CK-II-mediated stimulation of their enzyme activities in vitro.
PMID- 9657041
TI - Enhancement of the DNA damaging activity of N-nitrosodimethylamine by di-(2
ethylhexyl)phthalate in somatic cells in vivo of Drosophila melanogaster.
AB - The co-genotoxic effect of di-(2-ethylhexyl)phthalate (DEHP) was studied in an in
vivo Drosophila genotoxicity test. DEHP is categorized as a non-genotoxic
carcinogen. In this study, DEHP also did not show genotoxicity in Drosophila.
When larvae were simultaneously treated with DEHP and N-nitrosodimethylamine
(NDMA), the DNA damaging activity of NDMA was increased in the Drosophila DNA
repair test. Furthermore, DNA double strand breaks were increased by the same
treatment of Drosophila. These results suggest that DNA double strand breaks
cause the co-genotoxic effect of DEHP in Drosophila.
PMID- 9657042
TI - Formation of reactive oxygen intermediates might be involved in the trypanocidal
activity of gallic acid.
AB - We investigated the mechanism of the trypanocidal activity of gallic acid (GA).
GA-induced trypanocidal activity was significantly reduced by pretreatment with
superoxide dismutase (SOD) and/or catalase. The ESR technique with 5,5-dimethyl-1
pyrroline N-oxide (DMPO) as a spin trapping agent revealed that a DMPO-OH adduct
was detected in culture medium containing GA. The intensity of ESR signals of the
DMPO-OH adduct was increased in a time dependent manner. SOD also inhibited the
formation of GA-induced DMPO-OH adducts. Furthermore, GA enhanced DNA single
strand breaks induced by Fenton reagent. These results suggest the possibility
that GA acts as pro-oxidant for trypanocidal activity.
PMID- 9657043
TI - Metabolism and pharmacokinetics of orally administered saikosaponin b1 in
conventional, germ-free and Eubacterium sp. A-44-infected gnotobiote rats.
AB - The metabolic fate of saikosaponin b1 (1) was investigated using conventional,
germ-free and Eubacterium sp. A-44-infected gnotobiote rats. After the oral
administration of 1 to germ-free rats at a dose of 50 mg/kg, no metabolite was
detected in the plasma, the cecal contents or the cumulative feces through the
experiment. On the other hand, when 1 was orally given to the Eubacterium sp. A
44-infected gnotobiote rats, considerable amounts of its metabolites,
prosaikogenin A (2) and saikogenin A (3), were detected in the rat plasma with
the respective AUC0-10 h values of 17,424 and 22,260 pmol.min/ml, similar to the
case of its oral administration to conventional rats (AUC0-10 h values of 9,936
and 12,414 pmol.min/ml for 2 and 3, respectively). Furthermore, significant
amounts of both metabolites were detected in the cecal contents and the
cumulative feces of the gnotobiote and conventional rats, but not in those of the
germ-free rats, within 10 h after the administration. Fecal and cecal activities
of hydrolyzing 1 and 2 were found in the gnotobiote and conventional rats, though
there were no detectable activities in the germ-free rats. Accordingly, both
hydrolyzing activities in the intestinal bacteria, such as Eubacterium sp. A-44,
are essential for the appearance of 2 and 3 in the rat plasma and cumulative
feces, since orally administered 1 was poorly absorbed from the gastrointestinal
tract.
PMID- 9657044
TI - Antiosteoporotic activity of the stems of Sambucus sieboldiana.
AB - We previously found that a methanolic extract of the stems of Sambucus
sieboldiana inhibited bone resorption in organ culture. In this study, we further
fractionated the methanol extract guided by the activity towards bone resorption
stimulated by parathyroid hormone (PTH) in vitro. The ethyl acetate fraction
(EtOAc Fr.) of the methanolic extract inhibited PTH-stimulated bone resorption of
neonatal mouse bones, and the inhibitory activity was more potent than those of
other fractions. Oral administration of the EtOAc Fr. (50 and 100 mg/kg/d) to
ovariectomized (OVX) rat prevented the decrease in bone mineral density (BMD) of
the lumbar (L2-4) vertebra, indicating that the EtOAc Fr. is effective in vivo.
Furthermore, the EtOAc Fr. (50, 100 and 150 mg/kg/d) decreased the serum calcium
level elevated in low calcium dietary rats. The phenolic constituents of the
EtOAc fraction were examined for their inhibitory effect on bone resorption
stimulated by PTH in neonatal mouse bone. Among them, vanillic acid, vanillin and
coniferyl alcohol showed significant inhibitory effects on bone resorption. Of
the compounds examined, vanillic acid was found to have a significant inhibitory
effect on the decrease of BMD in OVX mice. Therefore, the EtOAc Fr. of S.
sieboldiana showed a suppressive effect on bone resorption in vitro and in vivo.
In addition, the inhibitory effects of the EtOAc Fr. on bone resorption may be at
least partly due to the inhibitory action of vanillic acid.
PMID- 9657045
TI - Enhanced in vitro percutaneous penetration of salicylate by ion pair formation
with alkylamines.
AB - The apparent octanol/water partition coefficient (APC) of salicylate (SA)
increased as the concentration of alkylamine (amyl, hexyl, heptyl, octyl and
nonylamine) in aqueous phase increased, presumably through intermolecular ion
pair formation between the negatively charged SA moiety and the alkylamine
cation. The true partition coefficient (TPC) and the formation constant (Kf) of
the ion pair were calculated from the partition data. The skin permeability of SA
increased as the APC of SA increased, when 20-fold molar excess of alkylamine was
added to the donor compartment. Permeability of ion pairs (PAB) from the aqueous
phase to a shed snake skin was estimated from the permeability data assuming 1:1
ion pair. The methylene group contribution to the free energy of transfer of ion
pairs from water to the shed snake skin was less than the reported value for
nonionized drugs. This suggests that the ion pair is more polar by nature than
nonionized molecules, even if ionic characteristics are masked to some extent by
ion pair formation.
PMID- 9657046
TI - Dose dependency in the gastrointestinal absorption of cefatrizine: correlation
between in vivo and in situ.
AB - We evaluated the dose-dependent (saturable) gastrointestinal absorption of
cefatrizine, an aminocephalosporin transported by peptide carriers, in rats by a
physiological mechanism-based approach to clarify its absorption characteristics
and to examine the in vitro (in situ)-in vivo correlation in intestinal
transport. With an increase in oral dose (mumol/5 ml/kg) from 5 (low) to 50
(high), the intestinal absorption rate constant (ka), which was estimated by
analysis of gastrointestinal disposition, decreased markedly, from 0.301 to 0.056
min-1. This decrease was ascribable to the saturability of intestinal membrane
transport, of which the concentration dependency in the perfused intestine was
similar in extent to the dose dependency in ka. However, the apparent absorption
rate constant (ka'), which was estimated by analysis of plasma concentrations
after oral administration, decreased only modestly from 0.037 to 0.023 min-1.
This was associated with the result that, at the low dose, ka' was far smaller
than ka and comparable with k(g) (gastric emptying rate constant), suggesting
gastric emptying-limited absorption. At the high dose, where intestinal
cefatrizine absorption was less efficient, ka' was closer to ka than k(g). It was
also observed that the bioavailability was close to unity, independent of dose,
suggesting that the intestinal transit time is long enough to achieve complete
absorption, even at the high dose, where intestinal cefatrizine absorption is
less efficient. Thus, it was found that the effect of saturability in the
intestinal transport of cefatrizine is apparently attenuated in its overall
gastrointestinal absorption because of the involvement of gastric emptying and
intestinal transit time as additional physiological factors to define absorption.
It was also found that a scaling factor is required to correlate the intestinal
membrane transport between in vitro (in situ) and in vivo, though this remains to
be verified to be utilized for developing oral drug delivery strategies and
optimizing oral drug therapy.
PMID- 9657047
TI - Hepatic extraction of tacrolimus in rats with experimental liver diseases.
AB - Tacrolimus, an immunosuppressive agent, is metabolized mainly in the liver and
has shown large intra- and interindividual pharmacokinetic variability. We
investigated the effect of liver dysfunctions on the pharmacokinetics of
tacrolimus in rats with experimental liver diseases. Experimental hepatic failure
was induced by CCl4-treatment or bile duct ligation. Tacrolimus (1 or 0.3 mg/kg)
was administered intravenously or intraportally to the rats (n = 5-6 per group),
and blood samples were collected over a 240-min period. The tacrolimus
concentrations in the blood were then measured by a high-performance liquid
chromatography-enzyme immunoassay. In the normal rats, the hepatic extraction
ratio of tacrolimus (EH) was dose-independent, ranging from 0.556-0.598 at 0.3
and 1.0 mg/kg doses. The EH were dose-dependent in the CCl4-treated rats and in
the bile duct-ligated rats: the EH at 1.0 mg/kg dose were 0.158-0.170 and those
at 0.3 mg/kg dose were 0.329-0.394. The intermediate EH of tacrolimus suggested
that the clearance of tacrolimus depends not only on hepatic intrinsic clearance
but also on hepatic blood flow. The present pharmacokinetic study also suggested
that the decrease of EH and the dose-dependence of EH contribute to the elevation
of blood tacrolimus concentrations and to the large variability in the
pharmacokinetics of tacrolimus after oral administration in hepatic dysfunctions.
PMID- 9657048
TI - Effectiveness and toxicity screening of various absorption enhancers using Caco-2
cell monolayers.
AB - We studied the enhancing and toxic effects of five different absorption enhancers
on the transport of FITC-dextran with an average molecular weight of 4000 (FD-4)
across Caco-2 cell monolayers, and their enhancing effects were also compared
with those in rat intestine. The enhancing and cytotoxic properties of these
enhancers were characterized using the following tests: measurement of the
permeability coefficients of FD-4 and the transepithelial electrical resistance
(TEER) in Caco-2, the release of cytosolic lactate dehydrogenase (LDH) and
intracellular mitochondrial dehydrogenase (MDH) activity. All the absorption
enhancers increased the permeability of FD-4 across Caco-2 cell monolayers and a
good relationship was observed between the enhancement and their toxic effects.
However, EDTA and Na-Cap were effective for improving the transport of FD-4
across Caco-2 cells without serious cytotoxicity. At concentrations with low
cytotoxicity, various absorption enhancers exihibited reversible effects on the
TEER values in Caco-2 cell monolayers, except for 50 mM sodium salicylate (Na
Sal). Moreover, we obtained a good correlation between the enhancement of these
enhancers in Caco-2 cell monolayers and in rat large intestine. This finding
indicated that the effectiveness of absorption enhancers in the Caco-2 monolayer
system was similar to an in vivo rat system. Therefore, the screening system
using Caco-2 cell monolayers is useful for examining the effectiveness and
toxicity of absorption enhancers.
PMID- 9657049
TI - Virus inactivation in superoxide dismutase preparations by ultraviolet light
irradiation.
AB - Viral inactivation in superoxide dismutase (SOD) derived from human red cells was
carried out by ultraviolet light C (UVC) irradiation. With 400 J/m2 UVC
irradiation, the titer of canine parvovirus (CPV, a nonenveloped virus), M13
bacteriophage (M13, a nonenveloped phage) and vesicular stomatitis virus (VSV, an
enveloped virus), which were spiked into SOD solution, were reduced by > 4.6
log10 (detection limit), 7.0 log10 and 6.2 log10, respectively. The SOD activity
was maintained and the band pattern of SOD on an electrophoresis gel was not
changed even by 1000 J/m2 UVC irradiation. These results indicate that UVC
irradiation is a promising method for the inactivation of both enveloped and
nonenveloped viruses in SOD preparations while maintaining its activity.
PMID- 9657050
TI - Formation of adenosine 3'-monophosphate in rat liver mitochondria.
AB - An unknown adenine-related compound (UKC) in rat liver mitochondria was
characterized. Based on the sensitivity to periodate oxidation, nuclease P1
digestion, property of fluorescence derivatization, elution behavior on different
separation modes of HPLC columns and the mass spectrum of purified UKC, the UKC
was identified as adenosine 3'-monophosphate (3'-AMP), an intracellular P-site
inhibitor of adenylate cyclase. 3'-AMP may be enzymatically produced from RNA in
rat liver mitochondria in temperature- and time-dependent manners. A partial
characterization of 3'-AMP forming enzyme is included.
PMID- 9657051
TI - Metabolism of puerarin and daidzin by human intestinal bacteria and their
relation to in vitro cytotoxicity.
AB - When puerarin or daidzin were incubated for 24 h with human intestinal bacteria,
two metabolites, daidzein and calycosin, were produced from them, respectively.
The metabolic time course of puerarin was as follows: at an early time, puerarin
was converted to daidzin, and then calycosin. The metabolic time course of
daidzin by human intestinal bacteria was also similar to that of puerarin. The in
vitro cytotoxicities of these metabolites, calycosin and daidzein, were superior
to those of puerarin and daidzein.
PMID- 9657052
TI - Effect of over-expressed hsp26 on cell growth of yeast.
AB - Mammalian small heat shock protein (s-hsp) has been suggested to participate not
only in stress tolerance but also in the growth regulation and differentiation of
cells. To confirm the role of s-hsp in cell growth, we investigated the
relationship between the expression of hsp26 and yeast cell growth. Cells lacking
constitutive hsp70, ssa1ssa2, have been known to have a poor growth rate and to
over-express hsp26 and some other hsps. We obtained several cell clones of
ssa1ssa2 whose doubling times were different from one another. The amount of
hsp26 was closely linked to the doubling time of ssa1ssa2 cells. This result
suggests that the expression of hsp26 modulates the growth rate of yeast cells
lacking constitutive hsp70, similarly to mammalian cells.
PMID- 9657053
TI - A protease sensitive region of plant and animal ribonucleases belonging to the
RNase T2 family.
AB - Recombinant RNase LE from tomato and squid liver RNase Tp, typical plant/animal
type RNases belonging to the RNase T2 family, were subjected to limited digestion
with several proteases, and the cleavage sites were analyzed by Edman
degradation. Recombinant RNase LE was cleaved specifically at the 24th Lys by
lysylendopeptidase and trypsin, and RNase Tp was cleaved at the 21st Glu by V8
protease. These cleavage sites are located very close to those where the cleavage
during preparation of several animal RNase T2 family enzymes was observed. From
this finding, it was concluded that the short segment around the 20th amino acid
residue in plant/animal RNases is located on the surface of the molecules and
forms loops, and is thus very sensitive to proteases.
PMID- 9657054
TI - Thalidomide promotes the release of tumor necrosis factor-alpha (TNF-alpha) and
lethality by lipopolysaccharide in mice.
AB - We investigated the in vivo effects of thalidomide on the production of tumor
necrosis factor-alpha (TNF-alpha). An in vivo systemic release of TNF-alpha
occurred after the injection of lipopolysaccharide (LPS) in male ddY mice, and
the TNF-alpha serum levels reached 652.2 +/- 75.7 pg/ml 90 min after the
injection of LPS (0.3 mg/kg, i. p.). When thalidomide (1, 3, or 6 mg/kg) was
administered intraperitoneally 3 h before the injection of LPS (0.3 mg/kg, i.
p.), thalidomide markedly enhanced LPS-induced TNF-alpha release in a dose
dependent manner. The TNF-alpha serum levels at 90 min were 640 +/- 58.6, 1985 +/
132.6, and 2795 +/- 203.5 pg/ml, respectively, compared to 628.6 +/- 64.4 pg/ml
in mice treated with LPS-alone. Pretreatment with a single injection of
thalidomide (1, 3, or 6 mg/kg, i. p.) dose-dependently increased the subsequent
mortality caused by a challenge with LPS (15 mg/kg, i. p.), a dose that caused
death in 10% of the control mice. We conclude that thalidomide enhances in vivo
TNF-alpha secretion and the lethality of LPS in mice.
PMID- 9657055
TI - Anthraquinones from Neonauclea calycina and their inhibitory activity against DNA
topoisomerase II.
AB - In a series of searches for DNA topoisomerase II inhibitors from naturally
occurring compounds, a wood extract of Neonauclea calycina MERR. (Rubiaceae)
showed a moderate effect in vitro. Purification of the extract resulted in the
isolation of seven known anthraquinones. The structures were characterized as
damnacanthal, rubiadin 1-methyl ether, nordamnacanthal, morindone, damnacanthol,
lucidin 3-O-primeveroside and morindone 6-O-primeveroside by spectral analysis,
respectively. Damnacanthal and morindone showed an intensive inhibitory effect
against topoisomerase II (IC50: 20 micrograms/ml and 21 micrograms/ml).
PMID- 9657056
TI - Trypanocidal effects of curcumin in vitro.
AB - During the course of study searching for the antiparasitic agents from natural
compounds, we found that curcumin showed cytotoxicity against African
trypanosomes in vitro. The LD50 values of curcumin were 4.77 +/- 0.91 microM for
bloodstream forms and 46.52 +/- 4.94 microM for procyclic forms of Trypanosoma
brucei brucei (GUTat 3.1 clone).
PMID- 9657057
TI - Effect of guarana on exercise in normal and epinephrine-induced glycogenolytic
mice.
AB - The tonic action of water Guarana extract, (Paullinia cupana MART.), was
investigated in normal, exercised, and epinephrine-induced glycogenolytic mice. A
water extract of Guarana (GW) (500 mg/kg) increased the blood glucose level (p <
0.001) and decreased the liver glycogen contents of mice 60 min after oral
maltose administration (p < 0.05). GW also significantly suppressed exercise
induced hypoglycemia (60 min: p < 0.05). However, GW did not affect the blood
glucose in epinephrine-induced glycogenolytic and exercise mice. These findings
indicate that the suppressive mechanism of hypoglycemia might be due to the
promotion of glycogen resolution.
PMID- 9657058
TI - The pragmatics of "madness": performance analysis of a Bangladeshi woman's
"aberrant" lament.
AB - A fine-grained analysis of the transcript of a Bangladeshi woman's lament is used
to argue for an anthropology of "madness" that attends closely to performance and
performativity. The emergent, interactive production of wept speech, together
with the conflicting use to which it is put by the performer and her relatives,
is linked problematically to performance genres and to ethnopsychiatric indexes
of madness. Tuneful weeping is taken by relatives to be performative of madness,
in a sense something like Austin's. Yet, exploration of the divergent linguistic
ideologies which are brought to bear on the lament not only enables more nuanced
ethnographic treatment but also has reflexive ramifications for medical and
psychological anthropology. This leads to a critique of the referentialism in our
own treatment of language. The role played by transparent reference is
overshadowed by indexicality and by dialogical processes of proposing and
resisting labels for speech genres attributed to the "mad."
PMID- 9657059
TI - Complexity and human health: the case for a transdisciplinary paradigm.
AB - Transdisciplinary thinking is an emerging philosophy underpinning health social
science. We advance a definition of transdisciplinary thinking and link it with
complexity theory. Complexity theory's concern with non-linear relationships,
interactive causality and emergent properties of systems compels researchers to
adopt a transdisciplinary perspective. We construct a generic framework for
analyzing health processes from diverse disciplines and apply it to coronary
heart disease in the Australian Coalfields. Insights from this analysis support
our argument that transdisciplinary thinking maximizes understanding of the
complexity of human health.
PMID- 9657060
TI - Symptoms of depression in elderly Korean immigrants: narration and the healing
process.
AB - This paper explores ways in which depressive symptoms are expressed by elderly
Korean immigrants in the USA. Depressed elderly Korean immigrants in the
Washington DC area were interviewed in depth to explore their conceptualizations
of depression in terms of explanatory models and semantic networks. The
expressions of depressive symptoms were influenced by linguistic and psycho-socio
cultural factors, therapeutic behaviors, and efficacy of treatment. The data were
interpreted in terms of traditional Korean medical principles, cosmological,
socio-cultural, and religious influences, and an individual's family structural
changes and acculturation. Findings indicate the construction of somatization
among Korean elders is more complex than is generally reported: in most cases, a
dynamic, holistic blend of processes appears to operate simultaneously, instead
of as somatization in isolation. Informants placed different degrees of emphasis
on psychologization or somatization, or the two combined. The roles of
personality, value orientation, intellect, emotion, economic status, degree of
acculturation, degree of dependence on children, living situation (with or not
with children), and self-will or self-confidence are important influences on the
depression symptoms in the psychologization-somatization continuum. The more self
directed the informants are, the more they psychologize; the more other-directed,
the more they seem to somatize. Names and symptoms of depression (a Western
concept) and popular illnesses (traditional Korean concepts) were used
interchangeably by the informants. When informants were asked to explain the
signs and symptoms of depression and sadness, some described symptoms similar to
the criteria of major depression in DSM-III (American Psychiatric Association),
while others gave different symptoms and ways of expressing them. Some informants
believed that symptoms and signs of depression can be concealed from others if
one chooses to do so. Many felt that manifestations of depression can be
controlled by willpower, personality, and self-care.
PMID- 9657061
TI - Cultural formulation of psychiatric diagnosis. Psychotic depression and
alcoholism in an American Indian man.
PMID- 9657063
TI - High-frequency FSH and LH pulses in obese menopausal women.
AB - We studied the pulsatile luteinizing hormone (LH) and follicle-stimulating
hormone (FSH) secretory patterns, at early or intermediate years of menopause in
seven normal women with different degrees of obesity, taking blood samples every
minute for 40 min to 2 h. The hormones were assayed with an immunoradiometric
assay (IRMA) system, analyzing with the cluster pulse algorithm. All women showed
hormone pulses every 8-10 min. In five of them were found periods of discrete
pulses with oscillations of high amplitude alternating with periods of pulses of
low amplitude. In two cases, the high-frequency oscillatory pattern with low
amplitude was found around low mean levels of 22.8 and 25.7 IU/L. The LH
oscillatory pattern also had a high frequency, but at a lower level, giving a
high FSH/LH ratio. The coincidence index of FSH with LH peaks was 76.6%. We
concluded that at menopause, the frequency of FSH and LH secretion increases with
a high FSH/LH ratio. Obese menopausal women may have the same high-frequency
oscillatory patterns, but at low levels.
PMID- 9657062
TI - Growth hormone. A paracrine growth factor?
AB - A number of tissues, including the brain, pituitary, immune system, placenta,
mammary gland, and testis, may be self-contained units of GH regulation,
production, and action. The production of GH and GH-releasing factors outside the
hypothalamo-pituitary axis complements, rather than replaces, the traditional
endocrine interactions between GH-releasing factors, GH, and its target tissues.
PMID- 9657064
TI - Identification of endothelin receptor subtypes in sheep choroid plexus.
AB - Endothelin (ET) and its G-protein-coupled receptors are distributed in a wide
variety of tissues, including the brain. In this study, we have identified and
characterized the endothelin receptor subtypes in sheep choroid plexus.
Competitive binding experiments using [125I]ET-1 and the receptor subtype
selective ligands, ET-1, ET-3, BQ-123, Sarafotoxin 6c, and [Ala1,3,11,15] ET-1
demonstrated the presence of both ETA and ETB receptor subtypes in the ratio of
30:70. In addition, a small fraction of the total binding sites exhibited
affinities for ET-1 in the subpicomolar range. Chemical crosslinking of [125I]ET
1 with bis(sulfosuccinimidyl)-suberate (BS3) to choroid plexus membranes revealed
the presence of two bands, with apparent molecular masses of 89 and 45 kDa,
corresponding to the ETA receptor, and three bands, with apparent molecular
masses of 75, 58, and 33 kDa, corresponding to the ETB receptor. Of considerable
interest was the finding that dimers of the [125I]ET-1-occupied ETA receptor
could be identified by crosslinking, as could apparent dimers and tetramers of
[125I]ET-1, but only when bound to receptor. In addition to mapping the
distribution of ET receptors in sheep choroid plexus, our results strongly
suggest that ET-1 binding to the ETA receptor leads to dimer formation.
PMID- 9657065
TI - Differential effects of tumor necrosis factor-alpha and interleukin-1 on 3 beta
hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase expression in mouse
Leydig cells.
AB - Immune-endocrine interactions are important to the regulation of Leydig cell
steroidogenesis. We have shown previously that both tumor necrosis factor-alpha
(TNF-alpha) and interleukin-1 beta (IL-1-beta) inhibit 8-bromo-cAMP-(8-Br-cAMP)
stimulated steroidogenesis in mouse Leydig cells. TNF and IL-1 both inhibit cAMP
stimulated testosterone production as well as mRNA and protein levels of
cholesterol side chain cleavage enzyme (P450scc) and 17 alpha-hydroxylase/C17,20
lyase (P450c17) in mouse Leydig cells. Neither TNF nor IL-1 affects basal levels
of P450scc mRNA and protein. In the present study, we tested the effects of TNF
and IL-1 on basal testosterone production and 8-Br-cAMP-stimulated 3 beta
hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase (3 beta HSD) expression
in Leydig cells. Purified and macrophage-depleted Leydig cells were cultured for
5 d with daily changes of media, and then treated with increasing concentrations
of recombinant mouse TNF or IL-1 in the presence or absence of 8-Br-cAMP (50
microM) for 24 h. The media were collected for testosterone RIA and RNA and
protein were extracted from cells. Basal testosterone production was inhibited by
TNF, but not IL-1. Treatment of Leydig cells with 8-Br-cAMP alone caused a marked
increase in 3 beta HSD mRNA, and protein levels. Both TNF and IL-1 inhibited cAMP
stimulated 3 beta HSD mRNA and protein levels, but only TNF inhibited basal 3
beta HSD expression. These results demonstrate that TNF and IL-1 have different
effects on basal steroidogenesis in Leydig cells and suggest that TNF-mediated
inhibition of basal testosterone production may be owing to the inhibition of
basal 3 beta-HSD expression in Leydig cells.
PMID- 9657066
TI - Regulation of the glucocorticoid receptor gene by the AP-1 transcription factor.
AB - The glucocorticoid receptor (GR) is a ligand-activated nuclear transcription
factor, and AP- 1 (Fos/Jun or Jun/Jun) is a transcription factor whose components
are nuclear proteins encoded by c-fos and c-jun protooncogenes. Serum stimulation
of serum-starved NIH 3T3 cells resulted in an approx 188-fold induction of c-fos
mRNA at 30 min and an approximately ninefold induction of c-jun mRNA at 1 h,
followed by an increase in GR mRNA levels at 3-12 hour (twofold). Sequential
induction of cFos, cJun, and GR protein levels also occurred. Overexpression of
the cFos protein in NIH 3T3 cells (NIH 3T3 [cFos 3] and NIH 3T3 [cFos 10]) caused
an increase in the endogenous GR protein. Previous and present studies showed
that a putative AP-1 site within the GR promoter binds AP-1 proteins (both Jun
and Fos family members). To address the molecular mechanism involved in
transcriptional activation of the GR gene, we investigated the relevance of AP-1
binding complexes in this activation and in overall regulation of GR gene
transcription. Transient transfection with a full length GR promoter linked to a
luciferase gene into both NIH 3T3 (cFos 3) and NIH 3T3 (cFos 10) cells gave rise
to an induction of luciferase activity. This induction was abolished following
mutation or deletion of the GR AP-1 site from the promoter. These findings
suggest that cFos is responsible for the induction of GR expression in serum
stimulated NIH 3T3 cells, and serum growth factors may stimulate GR transcription
by a cFos-dependent mechanism at the putative AP-1 site. These studies support a
role for the AP-1 transcription factor in regulating GR gene expression.
PMID- 9657067
TI - Stimulation of insulin and somatostatin release by two meglitinide analogs.
AB - Several meglitinide analogs are currently under investigation as potential
insulinotropic tools for the treatment of noninsulin-dependent diabetes. The
present study aimed to further insight into the effect of these agents on the
secretion of insulin, glucagon, and somatostatin by the isolated perfused
pancreas. Both repaglinide (0.01 microM) and A-4166 (1.0 microM) stimulated
insulin and somatostatin release, but failed to affect glucagon output, from
pancreases exposed to 5.6 mM D-glucose. The secretory response of the B- and D
cells to the hypoglycemic agents was much less marked than that caused by a rise
in hexose concentration from 5.6-16.7 mM. Although repaglinide was tested at a
concentration a hundred times lower than that of A-4166, the drug-induced
increase in both insulin and somatostatin secretion persisted for a longer time
after exposure to repaglinide, than to A-4166. The relevance of these findings to
the use of meglitinide analogs as antidiabetic agents is double. First, they
document that these drugs, although enhancing both insulin and somatostatin
release, do not provoke an undesirable stimulation of glucagon secretion. Second,
they indicate that even at a very low concentration, repaglinide provokes a
protracted insulinotropic action, thus suggesting that the reversibility of the
secretory response to this or other meglitinide analogs represents an intrinsic
molecular attribute, unrelated to either their biological potency or the relative
extent of B-cell stimulation.
PMID- 9657068
TI - Depriving neonatal rats of milk from early lactation has long-term consequences
on mammotrope development.
AB - The sudden appearance of prolactin-releasing cells during the early postnatal
period of the rat is initiated by a small milk-borne peptide. Depriving newborn
rats of this early milk factor severely retards mammotrope differentiation during
the neonatal period. In the present work, we extend our study of early milk
deprivation to the adult. To this end, newborn litters were crossfostered onto
mothers that had given birth the same day or one week earlier in order to deprive
pups in the latter group of early milk. At 5, 15, and 30 d of age, rats deprived
of such milk had decreased percentages of mammotropes (as measured by reverse
hemolytic plaque assay, RHPA) when compared to nondeprived animals (P < 0.05). By
45 d, the percentage of mammotropes was similar for the two crossfostered groups
(P > 0.1) and this persisted through d 60. Subsequently, we assessed the
secretory capacity of mammotropes from 60-d old rats to secretagogues and found
that early milk deprivation had no effect on basal prolactin release (P > 0.1),
but that it augmented hormone secretion evoked by thyrotropin-releasing hormone
(TRH, 100 nM; P < 0.01). The inhibitory response to dopamine (DA; 1 microM) and
the stimulatory response to angiotensin II (AGII; 100 nM) were not altered by
early milk deprivation (P > 0.1). Taken together, these results demonstrate that
factors in milk from early lactation are required for normal mammotrope
differentiation, and that the delay induced by early milk deprivation leads to
altered secretory function of mammotropes in adult animals.
PMID- 9657069
TI - Leukemia inhibitory factor (LIF) modulates pro-opiomelanocortin (POMC) gene
regulation in stably transfected AtT-20 cells overexpressing LIF.
AB - Leukemia inhibitory factor (LIF) levels are elevated in sepsis and correlate with
shock and poor prognosis. We have previously shown that lipopolysaccharide (LPS)
administration induces hypothalamic and pituitary LIF expression in vivo, which
is associated with the acute rise in circulating adrenocorticotrophic hormone
(ACTH) levels. As AtT-20 cells respond to LIF, we established murine LIF (mLIF)
stably transfected AtT-20 cell lines to study LIF regulation of pro
opiomelanocortin (POMC) expression and ACTH secretion. Our results show that mLIF
transfectants accumulated mLIF (up to 15.6 +/- 3.2 ng/mL after 24 h) as well as
increased ACTH secretion (up to 2.4-fold above control cells) in conditioned
medium. The magnitude of ACTH induction correlated with mLIF concentrations in
different transfectants (r = 0.75-0.88, p < 0.05). Moreover, mLIF transfectants
showed a higher sensitivity to CRH stimulation with an increased ACTH production
within 8 h (p < 0.05), whereas control cells were responsive to CRH at 24 h.
Additionally, mLIF transfectants exhibited a maximum threefold ACTH induction,
compared to 1.7-fold in control cells. Furthermore, mLIF transfectants have a
blunted dexamethasone-mediated inhibition of ACTH (35% inhibition in control
cells vs no inhibition in mLIF-transfected cells at 24 h). These findings support
and extend the previous observations of LIF acting at the pituitary level, and
indicate that mLIF stably-transfected AtT-20 cells are a useful model for
studying mLIF-mediated gene regulation in pituicytes.
PMID- 9657070
TI - Regulation of the 11 beta-hydroxysteroid dehydrogenase in the rat adrenal.
Decrease enzymatic activity induced by ACTH.
AB - Patients with ectopic ACTH syndrome often develop hypertension and hypokalemic
alkalosis with an abnormal increase in the ratio of plasma cortisol to cortisone,
indicating that 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activity is
inhibited. Inhibition of 11 beta HSD allows access of cortisol or corticosterone
to the mineralocorticoid receptor where it act as a mineralocorticoid. Two
isozymes, 11 beta HSD-1 and 11 beta HSD-2, have been cloned and characterized.
The rat adrenal expresses the mRNAs for 11 beta HSD-2 and, in lesser amounts, 11
beta HSD-1. We investigated the effect of ACTH on the 11 11 beta HSD-2 activity
in the rat adrenal. Rat adrenal cells zone fasciculata (ZF) were dispersed and
incubated separately with increasing concentrations of ACTH for 90 min, and
secretion of corticosterone (B) and 11-dehydrocorticosterone (A) in the media was
measured by enzyme-linked immunoabsorbent assays (ELISA). The conversion of [3H]B
to [3H]A in the presence of 0.5 mM NAD+ was evaluated in microsomes prepared from
dispersed cells preincubated for 30 min with cyanoketone and metyrapone followed
by incubation for 30 min with the same inhibitors, with and without 10 nM ACTH.
The dispersed cells of the ZF produced significant amounts of A which increased
with ACTH. The basal B/A ratio was 0.97 +/- 0.05. ACTH caused a concentration
dependent increase in the ratio of B/A with a maximum ratio of 9.58 +/- 0.20.
ACTH also inhibited the conversion of [3H]B to [3H]A in microsomes in which
endogenous B production was inhibited by cyanoketone and metyrapone. ACTH did not
change the K(m) for B conversion, but the Vmax was reduced significantly (1.73 +/
0.43 pmol/min. mg protein), indicating that ACTH suppressed the 11 beta HSD-2 in
a noncompetitive fashion. Dibutyryl cyclic AMP (dcAMP) also produced a
concentration-dependent increase in the B/A ratio, but various concentrations of
calcium did not affect the enzyme activity. In summary, adrenal cells treated
with ACTH results in a significant increase in the ratio of B/A in the ZF owing a
noncompetitive inhibition of the 11 beta HSD-2 via the ACTH receptor.
PMID- 9657071
TI - Neonatal exposure to coumestrol, a phytoestrogen, does not alter spermatogenic
potential in rats.
AB - The objective of this study was to determine the effects of neonatal exposure to
phytoestrogens on male reproductive function as adults. Male rats were injected
either with 100 micrograms coumestrol or DMSO (controls) daily during their first
5 d of life. Pituitary gland, testes, sex accessory organs, and blood were
collected on d 60 of life. Serum testosterone, LH, and FSH levels were determined
by RIA. Levels of steady-state mRNA for gonadotrophin subunits (LH beta and FSH
beta were determined by Northern blot analysis and quantified by a scanning
densitometer. Coumestrol had no effect on weights of testes and sex accessory
organs, or sperm count. Similarly, there were no significant differences among
serum concentrations of testosterone, LH beta and FSH of coumestrol-treated rats
and those of controls. Whereas steady state levels of LH beta mRNA in coumestrol
treated rats did not differ from those of controls, steady state levels of FSH
beta mRNA increased (37%) in treated animals. However, the augmented FSH beta
mRNA expression in coumestrol-treated rats did not negatively affect reproductive
potential in male rats. We conclude that neonatal exposure to coumestrol does not
alter reproductive organ structure or spermatogenic potential in male rats.
PMID- 9657072
TI - Relationships between dopamine-induced changes in cytosolic free calcium
concentration ([Ca2+]i) and rate of prolactin secretion. Elevated [Ca2+]i does
not indicate prolactin release.
AB - This study was undertaken to investigate the relationship between dopamine (DA)
induced changes in the cytosolic calcium concentration ([Ca2+]i) and the rate of
prolactin secretion using GH4ZR7, a rat pituitary cell line, which express only
one subtype of D2 receptor. GH4ZR7 cells were loaded with Fluo-3, a fluorescent
Ca2+ indicator, and then perifused with two different doses of DA (10(-7) mol/L
and 5 x 10(-4) mol/L). We monitored changes in [Ca2+]i and rate of prolactin
release simultaneously by attaching a spectrofluorometer to a dynamic perifusion
system. DA has stimulatory and inhibitory effect on prolactin secretion in GH4ZR7
cells; 10(-7) mol/LDA slightly increased [Ca2+]i and stimulated prolactin
release, whereas 5 x 10(-4) mol/LDA decreased [Ca2+]i and inhibited prolactin
secretion. When the cells were pretreated with pertussis toxin (PTX), 10(-7)
mol/L DA had no significant change in [Ca2+]i while stimulating prolactin
release, and 5 x 10(-4) mol/L DA reduced [Ca2+]i without having any significant
effect on the rate of prolactin secretion. The results of this study demonstrate
that changes in [Ca2+]i do not always correlate with the rate of prolactin
release from lactotrophs. The dissociation between [Ca2+]i and prolactin release
is somewhat expected considering the diverse role of [Ca2+]i and post-[Ca2+]i
events, which can change the rate of prolactin release.
PMID- 9657073
TI - The effect of GH therapy on the immunoreactive forms and distribution of IGFBP-3,
IGF-I, the acid-labile subunit, and growth rate in GH-deficient children.
AB - We have previously shown that the major correlates of growth following growth
hormone (GH) therapy in growth hormone-deficient (GHD) children are changes in
circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP
3), suggesting a synergistic interaction between IGF-I and IGFBP-3 (1). The first
aim of this project was to examine the molecular forms of IGFBP-3 and the acid
labile subunit (ALS), and to assess the changes in these molecular forms during
GH administration to GHD children. Plasma samples from prepubertal GHD patients,
prior to therapy and during the first year of GH treatment, were subjected to
Western ligand and immunoblot analysis. Densitometric analysis of Western ligand
blotting (WLB) showed a 76% increase in IGFBP-3 (p = 0.02), but a 56% decrease in
36-kDa IGFBP-2 (p = 0.03) during GH therapy. Western immunoblot (WIB) analysis of
IGFBP-3 revealed the presence of intact (40- to 45-kDa doublet) as well as a
proteolyzed (28-kDa) form of IGFBP-3 in the serum of GHD and healthy children.
Both immunoreactive forms of IGFBP-3 increased by 64% during GH therapy (intact p
= 0.003; proteolyzed p = 0.0001). WIB analysis of the ALS showed an 84-to 86-kDa
doublet, which increased by 41% with GH therapy (p = 0.01). The response to GH
therapy, as measured by the height velocity standard deviation score (SDS)
adjusted for bone age, correlated with the percent change in total IGFBP-3 (r =
0.772, p = 0.002 by WIB), intact IGFBP-3 (r = 0.845, p = 0.0005 by WLB; r =
0.541, p = 0.05 by WIB), and proteolyzed IGFBP-3 (r = 0.703, p = 0.007), as well
as with the percent change in ALS (r = 0.813, p = 0.014). The second aim of this
project was to assess the changes in distribution of the immunoreactive forms of
IGFBP-3 and IGF-I among the ternary (ALS/IGFBP-3/IGF) complex, the binary (IGFBP
3/IGF) complex, and uncomplexed IGF during the first year of GH therapy, and to
explore further the correlation with growth response to GH. Plasma samples, prior
to therapy and after the first year of GH treatment, were separated by neutral
size-exclusion chromatography and then subjected to IGFBP-3 immunoradiometric
assay (IRMA), IGFBP-3 WIB, and IGF-I IRMA analysis. IGFBP-3 increased in both the
ternary (p < 0.0001) and binary (p = 0.01) complexes, but there was a shift in
the percentage of IGFBP-3 from the binary to the ternary complex during GH
therapy. Both intact and proteolyzed forms of IGFBP-3 were found in both the
ternary and binary complexes, but the shift occurred primarily for the
proteolyzed (28-kDa) form (p = 0.001). There was a significant increase in IGF-I
in the ternary (p = 0.001) and binary (p = 0.005) complexes, but not in
uncomplexed IGF-I. The percentage of IGF-I in the ternary complex increased (p =
0.006), whereas the percentage of uncomplexed IGF-I decreased (p = 0.02), during
GH therapy. Growth rate, assessed by the height velocity SDS for bone age,
correlated best with the changes in ternary complex IGFBP-3 (r = 0.72, p = 0.01)
and ternary complex IGF-I (r = 0.56, p = 0.10). In conclusion, GH treatment of
GHD children results in significant increases of intact, proteolyzed, and total
IGFBP-3, as well as an increase in ALS, which all correlate with the growth
response to GH therapy. In addition, GH treatment results in increases in ternary
complex IGFBP-3 and IGF-I, which also correlate with the response to therapy. We
suggest that the formation of the ternary complex may be a determining factor in
the somatic growth response.
PMID- 9657074
TI - Thapsigargin shifts the Ca set point of parathyroid cells to lower extracellular
[Ca].
AB - The hypothesis that cytosolic calcium concentration ([Ca2+cyt]) is the primary
regulator of parathyroid hormone (PTH) secretion is supported by a number of
studies that show an inverse relationship between them. One agent shown to
inhibit PTH secretion is thapsigargin, a sesquiterpene lactone that raises
[Ca2+cyt] by inhibiting the Ca-ATPase that pumps Ca2+ from the cytosol into the
lumen of the endoplasmic reticulum. Thapsigargin may act on the parathyroid cell
other than to inhibit the Ca-ATPase, however, in ways that might also affect PTH
secretion. We have tested its effects on functional parameters, such as protein
synthesis, the exocytic machinery, and the ability of parathyroid cells to
respond to different concentrations of extracellular Ca2+ ([Ca2+ex]). In
particular, we have determined whether the inhibition of PTH secretion by
thapsigargin is independent of or is modulated by changes in [Ca2+ex]. The
results revealed no effects of thapsigargin on protein synthesis or the exocytic
mechanisms within 2 h of treatment, and showed that [Ca2+ex] can modulate PTH
secretion in the presence of thapsigargin. Its inhibition of PTH secretion,
therefore, appears to rest on its ability to shift [Ca2+cyt] to higher levels,
but the possibility that it interacts with the Ca receptor has not been
eliminated. The results support the hypothesis that the primary regulator of
steady-state PTH secretion is [Ca2+cyt].
PMID- 9657075
TI - Quantitative measurement of islet glucagon response to hypoglycemia by confocal
fluorescence imaging in diabetic rats: effects of phlorizin treatment.
AB - We have shown that the glucagon irresponsiveness to hypoglycemia in diabetic rats
is markedly improved by correction of hyperglycemia independent of insulin. In
contrast, normalization of glycemia by insulin did not improve this response. To
find out whether these glucagon responses reflect changes in islet glucagon, we
directly quantified glucagon area and content in each pancreatic islet by using
fluorescent immunostaining and computerized image analysis with confocal laser
scanning microscopy (CLSM). The pancreases were analyzed in four groups of rats.
1. Normal controls (NC, n = 4), streptozotocin (65 mg/kg) diabetic rats. 2.
Diabetic untreated (DU, n = 4). 3. Diabetic Phlorizin-treated, (0.4 g/kg), twice
daily for 4 d (DP, n = 4). 4. Diabetic insulin-treated, using sustained release
(2-3 U/d) insulin implant for 5 d (DI, n = 4). Basal plasma glucose was 7.4 +/-
0.3 mM in NC, increased to 14.5 +/- 2.2 mM in DU, which was normalized in DP (5.5
+/- 0.5) and DI (6.7 +/- 0.8). Acute hypoglycemia (H) was induced by i.v. insulin
injection. The rats were sacrificed 2 h after insulin injection and the pancreas
was removed. By imaging with CLSM, we quantified: 1. Percent of glucagon
containing A-cell area/islet area, 2. Fluorescence intensity per islet area,
which indicated glucagon content in the islet. 3. Fluorescence intensity per
glucagon area indicating glucagon concentration in A-cells. In NC, glucagon
containing A cell area was 21 +/- 2% of the islet area, and glucagon intensity
and concentration was 11 +/- 1 U and 36 +/- 3.0 U, respectively, in basal (O)
state and did not change in (H). In DU, glucagon area increased 183% (O) and 166%
(H), and islet glucagon intensity increased by 235% (O) (p < 0.05), but decreased
to 135% in H. Glucagon area in DP and DI did not differ significantly from DU.
However, hypoglycemia in DP increased glucagon intensity in islet further to 306%
of normal control (p < 0.05), suggesting marked increase in glucagon content
indicating increased synthesis. In contrast, DI compared to DP showed a decrease
in glucagon intensity in islet (46 +/- 3, DP to 22 +/- 2 DI; p < 0.05) in (H)
state. Glucagon concentration followed the same pattern as its intensity.
CONCLUSION: 1. Increase in islet glucagon content in diabetic rats was associated
with increase in glucagon containing A-cell area per islet. 2. Phlorizin-induced
insulin independent correction of hyperglycemia increased glucagon content per
islet in hypoglycemic state. This, in part, probably contributed to improved
glucagon response to hypoglycemia observed earlier 3. Normalization of glycemia
with insulin reduced glucagon content of each islet during hypoglycemia. This may
explain, in part, unresponsiveness of glucagon to hypoglycemia often observed in
insulin-dependent diabetes mellitus (IDDM) with intensive insulin therapy.
PMID- 9657076
TI - Hormonal modulation of apoptosis in the rat adrenal gland in vitro is dependent
on structural integrity.
AB - The intact rat adrenal gland in short-term (3-h) organ culture may be amenable
for the identification of factors involved in regulating adrenal cell apoptosis
under defined conditions. In this model, culturing in the absence of trophic
support (basal; control) triggered apoptosis in the intact rat adrenal gland;
oligonucleosome formation, a measure of apoptosis, was 56.4-fold greater than
that of glands snap-frozen at the start of incubation. Angiotensin II (Ang II)
(100 nM) enhanced apoptosis by 67% over control. By contrast, adrenocorticotropin
(ACTH) (100 nM) attenuated basal apoptosis by 59% and antagonized the enhanced
apoptosis induced by Ang II back to the control level. Quartering of the glands
enhanced basal oligonucleosome formation 182.2% greater than that of intact
glands. Interestingly, quartering of the glands abolished the influences of Ang
II and ACTH on apoptotic DNA fragmentation, but did not alter ACTH-induced
corticosterone secretion. These data suggest that some level of gross adrenal
structural information or compartmentalization, sufficiently disrupted by
quartering, is required for the hormonal modulation of adrenal cell survival.
PMID- 9657077
TI - Role of advanced glycation end products in aging collagen. A scanning force
microscope study.
AB - The collagen structure of young and old rats was examined using a scanning force
microscope (SFM). Rat tail tendons of 8- and 24-month-old Wistar rats were frayed
by two blades and examined using a Nanoscope III SFM. In the same tendons, the
pentosidine concentrations, a marker of the Maillard reaction, were determined by
HPLC. The SFM inspection of native fibrils produces images of collagen bundles,
with parallel fibrils. The diameters of old rat collagen fibrils were large in
comparison to the young ones. Moreover, fibrils obtained from old rats exhibited
the same band interval, while the depth of the gap between two overlap zones
showed a higher mean value with respect to young collagen. The pentosidine
concentration was also higher in the old than in the young tendons. In
conclusion, in the presence of an increased concentration of advanced glycation
end products, significant structural alterations have been observed in old
fibrils.
PMID- 9657078
TI - Influence of age on oxidative bursts (chemiluminescence) of polymorphonuclear
neutrophil leukocytes.
AB - The release of reactive oxygen species (ROS) during neutrophil oxidative bursts
is the last of a sequence of different steps leading to the neutralization of
pathogen microorganisms. Using luminol-amplified chemiluminescence (LACL), the
oxidative burst activity of neutrophils in elderly people (> or = 75 years) was
compared with that in younger controls (39 years on average) after activation
with both particulate (Candida albicans) and soluble (formyl-methionyl-leucyl
phenylalanine; fMLP) stimulants. After Candida stimulation, a reduction in LACL
was observed in the elderly subjects in comparison with the controls, but the
difference did not reach statistical significance. After fMLP stimulation, the
reduction in LACL was significant, thus suggesting that the Candida pathway of
chemiluminescence production seems to be less affected than the fMLP pathway.
This finding raises questions concerning the complex differences in the pathways
of cell killing and ROS generation, and their efficacy in the elderly. Various
possible explanations are discussed, all of which need further investigation.
PMID- 9657079
TI - Age-related changes in gastric mucosal repair and proliferative activities in
rats exposed acutely to aspirin.
AB - The present study was designed to determine whether there are any age-related
changes in the repair of acute gastric mucosal injury induced by aspirin in
Fischer 344 rats. We have also examined the influence of aging on gastric mucosal
proliferative activities, a major component of gastric mucosal defense and repair
mechanisms. Our data demonstrated that aging was associated with significant
delays in both resolution of gross mucosal injury and regeneration of the injured
gastric mucosa. However, there were no correlations between the regeneration of
the injured gastric mucosa and gastric mucosal expression of proliferating cell
nuclear antigen and transforming growth factor-alpha immunoreactivities.
PMID- 9657080
TI - Total knee arthroplasty in the elderly: patients' self-appraisal 6 and 12 months
postoperatively.
AB - The objective of this work was to study patients' self-appraisal of total knee
arthroplasty (TKA) 6 and 12 months postoperatively, and to establish which
factors determine dissatisfaction from surgery. The study group consisted of 79
patients subjected to TKA who underwent rehabilitation in a specialized
institution from which they were discharged home after becoming independently
ambulatory and capable of independent home care. Data were collected by
interviews and physical examinations which were conducted upon admission to the
rehabilitation program and at the patients' homes 6 and 12 months
postoperatively. Descriptive statistics and logistic regression were applied for
data analysis. Results of the 1-year follow-up indicated a decrease in the
prevalence of pain in the postoperated knee and improvement in ambulatory
capacities. The frequency of reliance on a walking aid and the prevalence of pain
in the nonoperated knee were not substantially changed, however. In 27% of the
subjects pain in the nonoperated knee had worsened at 1 year. One third of the
respondents expressed dissatisfaction from the operation. Outcomes of the
logistic regression analysis pointed to pain in both the ipsi- and contralateral
knee and to the limitations in using stairs as the variables which significantly
affected the levels of dissatisfaction 1 year postoperatively. Dissatisfaction
could have resulted from inappropriate expectations from either
misinterpretations or limited prior knowledge of the likely results of the
operation.
PMID- 9657081
TI - Peripheral serotonin levels in women: role of aging and ethnicity.
AB - Serotonin has been implicated to play an important role in regulating emotions
and behavior, and it is well accepted that the platelet serotonergic system
mirrors the presynaptic central serotonergic system. Since prevalence of
psychiatric problems increases with age and women are known to be more vulnerable
than men, the present investigation was carried out to study the relationship
between serotonin activity and age in women. Levels of serotonin (5
hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA)
were measured in platelets and plasma in women (n = 49) aged 40-84 years (30
women aged 40-60 years and 19 women aged 61-84 years). There was a significant
age difference between the two groups (mean: 47.6 +/- 5.91 years in the younger
and 73.0 +/- 6.83 years in the older women, respectively, p < 0.00001). Platelet
5-HT as well as 5-HIAA levels were significantly higher in older women as
compared to those in the younger women (89.41 +/- 21.95 ng/10(8) platelets in
younger vs. 112.9 +/- 36.07 in older women, p < 0.02, and 1.20 +/- 1.10 in
younger vs. 2.19 +/- 1.88 ng/10(8) platelets in older women, p < 0.05,
respectively). Pearson correlation coefficients determined in the combined group
(n = 49) showed a significant positive correlation between platelet 5-HT and age
(r = 0.31, p < 0.03). Plasma 5-HT levels on the other hand were lower in older
women compared to those in the younger women (4.50 +/- 3.20 in younger vs. 1.04
+/- 1.28 ng/ml plasma in older women, p < 0.0001) and a significant negative
correlation was observed between plasma 5-HT and age (r = -0.44, p < 0.002).
Plasma 5-HIAA concentration did not differ between the two groups. Platelet 5-HT
levels in the younger group were independent of ethnicity. Since high serotonin
activity has also been associated with psychiatric problems, our results of
increased concentration of platelet 5-HT as well as 5-HIAA with age may have
implications in predisposing aging women to behavioral/psychiatric problems.
PMID- 9657082
TI - Effects of central nervous system polypharmacy on falls liability in community
dwelling elderly.
AB - BACKGROUND: While central nervous system (CNS) active medications such as
psychotropics and narcotic analgesics have been implicated in contributing to
falls in older adults, the combined effect of multiple CNS-active medications has
not been investigated. The purpose of this study was to examine the influence, in
community-dwelling elderly, of (1) taking multiple CNS-active medications on fall
liability and (2) individual classes of CNS-active medications (using discrete
drug classification) on the risk of falls after controlling for important
confounders--age, mobility, cognition and depression. METHODS: 305 community
dwelling male veterans (age: 70-104) were screened at study entry for mobility,
cognition and depression. CNS-active medications were categorized as
benzodiazepines, other sedative-hypnotics, neuroleptics, tricyclic
antidepressants, and opioid analgesics. Subjects were prospectively followed for
6 months to monitor falls; at the end of this time period, subjects were
classified as fallers (at least one fall) or nonfallers. The relationship between
CNS-active drug use and falls was examined using multivariable analyses. RESULTS:
The risk of falls was significantly greater in CNS-active medication users as
compared with nonusers. Adjusted odds ratio for one CNS-active drug was 1.54 (95%
confidence interval 1.07-2.22) and for two or more agents 2.37 (95% confidence
interval 1.14-4.94). CONCLUSIONS: In community-dwelling elderly, the use of
multiple CNS-active medications is associated with enhanced falls liability, over
and above the use of one CNS-active drug alone. This apparent dose-response
relationship provides support for causality.
PMID- 9657083
TI - Effects of age on gastric alkaline and nonparietal fluid secretion in humans.
AB - Little is known about the effect of age on gastric alkaline and nonparietal
secretion. Using a previously validated technique, we prospectively measured
gastric HCO3- and nonparietal volume secretion, as well as secretion of H+, Na+,
K+, and Cl-, in 114 healthy human beings over a wide age range (18-82 years).
Each subject had normal oxyntic mucosal histology, was on no medication known to
affect gastric secretion, and was studied under both basal (fasting) conditions
and following stimulation of gastric H+ secretion by pentagastrin. There was a
significant (p < 0.05) decline in gastric HCO3-, Na+, and nonparietal fluid
secretion with advancing age, but not in H+, K+, Cl- or parietal fluid secretion.
As a consequence of reduced gastric HCO3- and nonparietal fluid secretion, mean
H+ concentrations in gastric juice increased significantly with advancing age.
Thus, in healthy subjects with normal gastric histology, advancing age was
associated with a significant decline in gastric HCO3-, Na+, and nonparietal
fluid secretion, resulting in an increase in gastric acidity (H+ concentration).
PMID- 9657084
TI - Effect of short-term recombinant growth hormone administration on plasma
lipoproteins in elderly adults.
AB - To characterize the effects of recombinant human growth hormone (rhGH) on plasma
lipids and lipoproteins, rhGH was administered daily at a dose of 40
micrograms.kg-1 (Genentech) for 14 days in 7 healthy elderly male (67.4 +/- 1.9
years, 75.8 +/- 2.6 kg) adults. Six other healthy males (63.9 +/- 0.7 years, 77.8
+/- 3.8 kg) served as concurrent controls. Total plasma cholesterol (TC),
triglycerides (TG), very-low-density lipoprotein-cholesterol, low-density
lipoprotein-cholesterol, high-density lipoprotein-cholesterol, very-low-density
lipoprotein-TG (VLDL-TG) and apolipoprotein AI and apolipoprotein B were
determined after an overnight fast before and after the 14-day period of rhGH
administration. Subcutaneous rhGH administration was physiologically effective,
as shown by a threefold increase in insulin-like growth factor-I (from 110.8 +/-
8.2 to 355.5 +/- 41.6 ng.ml-1; p < 0.05). Plasma fasting insulin also increased
from 38.0 +/- 6.5 to 129.9 +/- 43.8 mumol.l-1 (p < 0.05) at the end of the 14
days of rhGH treatment. With respect to plasma lipid/lipoprotein changes, rhGH
administration increased plasma TG levels (from 1.5 +/- 0.3 to 2.2 +/- 0.4 mmol.l
1; p < 0.05) and VLDL-TG (from 1.1 +/- 0.3 to 1.8 +/- 0.4 mmol.l-1; p < 0.05),
but did not change TC (from 5.0 +/- 0.4 to 5.2 +/- 0.3 mmol.l-1) or any other
lipid/lipoprotein variables measured. No significant lipid changes were noted in
the control group over the 14-day period. These data suggest that short-term rhGH
treatment significantly alters plasma variables of TG profile, perhaps by
altering metabolic parameters (i.e. synthesis and/or clearance rates) of VLDL
metabolism.
PMID- 9657085
TI - Risk factors for major injurious falls among the home-dwelling elderly by
functional abilities. A prospective population-based study.
AB - BACKGROUND: In order to identify the risk factors essential for preventing major
injurious falls, the associations between injurious falls and certain factors
were assessed among disabled and independent elderly, respectively, who had
fallen during a 2-year period. METHODS: A prospective population-based study was
conducted in five rural northern Finnish municipalities. The series consisted of
all inhabitants aged 70 years or over, initially 979 persons. During a 2-year
follow-up period, all injurious falls were recorded on the basis of telephone
contacts, diary reporting and a review of the medical records of the
participants. RESULTS: Thirty percent of the subjects having fallen sustained a
major injury. The multivariate model applied to the disabled elderly showed the
following variables to be related to a high risk for major injurious falls:
divorced, widowed or unmarried marital status (odds ratio = 2.2), a low body mass
index (odds ratio = 3.1), incomplete step continuity (odds ratio = 2.2), poor
distant visual acuity (odds ratio = 2.3) and the use of long-acting
benzodiazepines (odds ratio = 2.4). Among the independent elderly, the risk of a
fall resulting in major injury was high among the subjects who had peripheral
neuropathy (odds ratio = 2.5) or were suffering from insomnia (odds ratio = 4.1).
CONCLUSIONS: The risk factors for major injuries in fall occurrences differ
between the disabled and independent elderly. Preventive measures should be
targeted according to the disabilities of the population.
PMID- 9657086
TI - Effects of low-impact, moderate-intensity exercise training with and without
wrist weights on functional capacities and mood states in older adults.
AB - This study examined the effects of low-impact, moderate-intensity exercise
training with and without wrist weights (0.68 kg.wrist-1) on functional
capacities and mood states in older adults (age 68.6 +/- 5.6, mean +/- SD).
Twenty-three senior citizens residing in the community were randomly assigned to
wrist weight (WW; n = 12) and no-wrist weight (NW; n = 11) exercise groups while
11 matched subjects served as non-exercise controls (NE). Exercise training was
performed for 10 weeks, 3 days/week, for 60 min/session and consisted of low
impact aerobic dance (50-70% of maximal heart rate) combined with exercises to
promote muscular fitness, flexibility, and balance. Before and after the
intervention, each participant's aerobic fitness, muscular strength, flexibility,
static and dynamic balance, skinfold thickness, and psychological mood states
were assessed under standardized testing conditions. Exercise training resulted
in significant improvements in peak oxygen uptake, lower extremity muscle
strength, and psychological vigor (p < 0.05) but did not affect other fitness
components (p > 0.05). There were no differences between the WW and NW exercise
groups for any of the same variables studied (p > 0.05). No significant pre- to
post-test changes were found for the NE control group (p > 0.05). It is concluded
that 10 weeks of low-impact, moderate-intensity exercise training of the type
that can be considered well-rounded in nature provides a sufficient stimulus to
augment aerobic fitness, beneficially affects leg strength, and increases
feelings of vigor in older adults. The present observations indicate that the use
of light wrist weights has no beneficial or adverse effects on the measured
training outcomes.
PMID- 9657087
TI - Deficiency of the growth hormone-insulin-like growth factor-I axis potentially
involved in age-related alterations in body composition.
PMID- 9657088
TI - Hepatocyte death in hepatocarcinogenesis.
PMID- 9657089
TI - Chronic cholestasis in rats induces anhedonia and a loss of social interest.
AB - Central fatigue commonly occurs in patients with primary biliary cirrhosis (PBC)
and correlates closely with depression, and cholestatic rats exhibit central
fatigue. Therefore, we undertook a series of experiments in both rats with
cholestasis caused by bile duct resection (BDR) and sham-resected controls (15
days after surgery) to determine if experimental cholestasis is associated with
symptoms of depression that can be modeled in rats, namely anhedonia (loss of
pleasure) and the loss of social interest. BDR rats exhibited significant
anhedonia compared with sham controls as indicated by a loss in their preference
for consuming a saccharin solution, a highly desirable drink for rats.
Furthermore, social interest was examined by determining the time BDR or sham
rats spent investigating a juvenile rat in an open-field apparatus compared with
the time spent on nonsocial behaviors. BDR rats exhibited significantly reduced
time spent in social investigation and significantly more time in nonsocial
behaviors than did sham rats. Major depression in humans is often associated with
elevated circulating glucocorticoid levels and impaired glucocorticoid feedback.
Therefore, we measured these parameters in BDR and sham rats and found a striking
elevation in circulating glucocorticoid levels in BDR compared with sham animals.
However, elevated circulating glucocorticoid levels in BDR rats suppressed
normally in response to exogenous dexamethasone, indicating intact glucocorticoid
feedback control at the pituitary level in BDR rats. In summary, we have
identified behaviors in cholestatic rats that are consistent with those seen in
depression.
PMID- 9657090
TI - Hepatic bile versus gallbladder bile: a comparison of protein and lipid
concentration and composition in cholesterol gallstone patients.
AB - Many studies have demonstrated that gallbladder bile (but not hepatic bile) of
animals or patients with cholesterol gallstones contains higher protein
concentrations than does gallbladder bile of control patients without stones or
with pigment stones. The underlying defect has not been elucidated. To establish
whether there is net production or net absorption/degradation of protein by
gallbladder epithelium for different classes of protein, paired samples of
hepatic and gallbladder bile were obtained from fourteen patients with
cholesterol gallstones during elective cholecystectomy. In these paired samples,
lipid and protein composition were determined. To obtain the concentration ratio
(CR) of protein and lipid, its concentration in the gallbladder was divided by
the concentration determined in the paired hepatic bile sample. The CR of bile
salts was used as a parameter for water absorption in the gallbladder. Of the
biliary proteins that were determined only mucin, albumin, immunoglobulin (Ig) G,
and aminopeptidase N appeared to increase in the gallbladder from another cause
than water absorption. A strong correlation was found between mucin, albumin, and
IgG. Haptoglobin, alpha1-acid glycoprotein, IgM, and IgA appeared to be absorbed
by gallbladder epithelium in the majority of patients. In cholesterol gallstone
patients, total protein concentration in gallbladder bile of cholesterol
gallstone patients is increased when compared with hepatic bile. The increase in
protein concentration cannot be explained for all bile samples solely by water
absorption. In this study we show that the defect is largely caused by a
selective increase in albumin, mucin, and IgG. All other proteins which were
investigated are taken up by the gallbladder.
PMID- 9657091
TI - The diagnostic and predictive value of ascites nitric oxide levels in patients
with spontaneous bacterial peritonitis.
AB - Nitric oxide (NO) is a messenger molecule involved in pathogen suppression.
Cirrhosis is characterized by an increased risk for infections, including
spontaneous bacterial peritonitis (SBP). The role of NO in the infections that
develop in cirrhosis has not been clearly established. The aim of this study was
to investigate the utility of measuring ascites NO in the diagnosis of SBP and/or
in determining the predisposition of cirrhotic patients to develop this
infection. Nitric oxide metabolites (nitrites + nitrates [NOx]) were measured by
chemiluminescence in 105 ascites samples obtained from 87 cirrhotic patients and
in 87 simultaneously obtained serum samples. Ascites NO levels were not
significantly different among ascites from patients with SBP (n = 39; median, 48
micromol/L), patients with sterile ascites (n = 54; median, 42 micromol/L), and
samples obtained after patients with SBP had been treated (n = 12; median, 62
micromol/L). No differences in ascites NO levels were observed between culture
positive and culture-negative peritonitis. Among 50 patients with sterile ascites
on initial paracentesis, 7 patients developed peritonitis during follow-up; no
differences in baseline NO levels were observed between patients who developed
peritonitis (median, 46 micromol/L) and those who did not (median, 41
micromol/L). Among patients with SBP, mortality was significantly higher in those
with NO levels >60 micromol/L. A very significant direct correlation was found
between ascites and serum NO levels (r2 = .86). In conclusion, ascites NO levels
in cirrhotic patients are not useful either to diagnose or to determine
predisposition to SBP. Rather, ascites NO levels reflect serum levels, are higher
in cirrhotic patients with more severe liver disease, and may be a useful
prognostic marker.
PMID- 9657092
TI - Development of pseudointima and stenosis after transjugular intrahepatic
portasystemic shunts: characterization of cell phenotype and function.
AB - The clinical utility of transjugular intrahepatic portasystemic shunts (TIPS) is
frequently complicated by the ingrowth of tissue into the stent lumen, causing
stent stenosis. These studies were undertaken to define the cellular and matrix
components of the pseudointima, define the phenotype and function of the
mesenchymal cells in the pseudointima and maintain them in culture, and to study
the differences between stenotic and nonstenosed stents. A total of 35 stents
were evaluated. TIPS pseudointima were examined histologically, by
immunohistochemistry and in situ hybridization to determine the cellular and
connective tissue constituents. Mesenchymal cells were grown from tissue within
the TIPS and around it, and their phenotype was studied and compared with control
smooth muscle cells and fibroblasts. Masson's trichrome staining of histological
sections demonstrated that TIPS tissue was composed of collagen and palisades of
mesenchymal cells and was lined by an endothelium. Immunostaining demonstrated
strong and uniform alpha-smooth muscle staining in TIPS mesenchymal cells and
peri-TIPS cells. Type I procollagen mRNA expression was demonstrated in
mesenchymal cells in and around the stent by in situ hybridization. TIPS
mesenchymal cells secreted less radiolabeled fibronectin, and far more type III,
relative to type I, collagen compared with peri-TIPS cells. TIPS cells also
expressed high levels of type III procollagen mRNA compared with peri-TIPS cells.
There was no difference between stenotic stents and nonstenosed stents with
respect to clinical features, time from stenting, gross morphology, histology,
presence of bile fistulae, and cell phenotype. However, smooth muscle cells (SMC)
from stenotic stents demonstrated both greater cell proliferation and collagen I
and III secretion compared with those from nonstenosed stents. These data
demonstrate that TIPS stenosis results from an accumulation of collagen and
proliferation of SMC within the stent lumen.
PMID- 9657093
TI - Optimal timing of liver transplantation for primary biliary cirrhosis.
AB - In 1989, we reported on the efficacy of liver transplantation in primary biliary
cirrhosis (PBC) by demonstrating that the actual patient survival following
transplantation was significantly better than without transplantation as
predicted by a mathematical survival model ("Mayo natural history model"). Our
aim in this investigation was to determine an optimal time to perform liver
transplantation in PBC. One hundred forty-three patients with PBC undergoing
liver transplantation were followed prospectively. Disease severity was measured
immediately before transplantation by a summary score ("risk score") used in the
Mayo natural history model, namely age, bilirubin, albumin, prothrombin time, and
the presence or absence of edema. Proportional hazards analyses were performed
assessing patient survival following transplantation. The influence of disease
severity immediately pretransplantation on resource utilization for liver
transplantation was assessed. Compared with our report in 1989, liver
transplantation was performed at an earlier stage of disease (e.g., median risk
score: 7.5 vs. 8.3; P < .01). Following transplantation, patient survival
probabilities at 1, 2, and 5 years were 93%, 90%, and 88%, respectively. In the
proportional hazards analysis, the risk of death following transplantation
remained low until reaching a risk score of 7.8. In contrast, risk scores greater
than 7.8 were associated with a progressively increased mortality. Resource
utilization measured by the days in the intensive care unit (ICU) and hospital
and the requirement for intraoperative blood transfusions was significantly
greater in recipients who had higher risk scores before transplantation. Our data
suggest that an optimal timing for liver transplantation, as determined by
patient survival and resource utilization, appears to be at a risk score around
7.8 in patients with PBC.
PMID- 9657094
TI - Increased cerebrovascular resistance in cirrhotic patients with ascites.
AB - Studies assessing regional hemodynamics in patients with cirrhosis and ascites
have shown vasodilation in the splanchnic circulation and vasoconstriction in the
renal circulation and in the brachial and femoral artery vascular territories.
The aim of this study was to assess the cerebral vascular resistance in cirrhotic
patients with ascites. The resistive index in the middle cerebral artery (an
index of the cerebral vascular resistance) and in a renal interlobar artery were
measured by Doppler ultrasonography in 7 healthy subjects: 13 patients with
compensated cirrhosis and 24 patients with ascites (13 with renal failure). The
arterial blood pressure and the activity of the renin-angiotensin and sympathetic
nervous systems, as estimated by plasma renin activity and plasma norepinephrine
concentration, respectively, were also measured. The resistive index in the
middle cerebral artery was significantly increased in patients with ascites (0.68
+/- 0.05, mean +/- SD) as compared with patients without ascites (0.60 +/- 0.01,
P < .05) and with healthy patients (0.52 +/- 0.01, P < .01). Renal resistive
index was also increased in patients with ascites (0.77 +/- 0.01) compared with
the other two groups (0.68 +/- 0.02 and 0.62 +/- 0.00, respectively; P < .001).
The resistive index in the middle cerebral artery showed a direct correlation
with renal resistive index (r = .73, P < .01), plasma renin activity (r = .61, P
< .01), and norepinephrine (r = .53, P < .01). The resistive index in the middle
cerebral artery showed an inverse correlation with mean arterial pressure (r =
.45, P < .01). These results indicate that in patients with cirrhosis and ascites
there is a cerebral vasoconstriction which is probably related with the arterial
hypotension and the overactivity of vasoconstrictor systems.
PMID- 9657095
TI - Subclinical hepatic encephalopathy impairs daily functioning.
AB - Subclinical hepatic encephalopathy (SHE) is assumed to have a negative effect on
patients' daily functioning; therefore, treatment is recommended. However, no
studies have been performed that document the clinical relevance of SHE. We
performed a study in which the prevalence of SHE was determined in 179
outpatients with cirrhosis using two psychometric tests (Number Connection Test
Part A [NCT-A] and the Digit Symbol Test [DGT]) and automated analysis of the
electroencephalogram (EEG). SHE was defined by the presence of at least one
abnormal psychometric test and/or abnormal slowing of the EEG. The influence of
cirrhosis and SHE on patients' daily functioning was assessed using the Sickness
Impact Profile (SIP) questionnaire. The distribution of SIP scores of the
patients with cirrhosis differed from the reference scores of the general
population. Patients with cirrhosis and SHE (n = 48) reported significantly more
impairment in all 12 scales of the SIP, in the psychosocial subscore, the
physical subscore, as well as in the total SIP score, compared with cirrhotic
patients without SHE (n = 131). Multivariate analysis taking into account
severity of liver disease (Child-Pugh score), presence of varices, and alcoholic
etiology, showed that SHE independently was related to a diminished total SIP
score. The reproducibility of the SIP was high when the test was repeated after a
3-month period. We conclude that SHE implies impaired daily functioning and
warrants attempts at treatment.
PMID- 9657096
TI - Sorbitol as a test substance for measurement of liver plasma flow in humans.
AB - The objective of this study was to evaluate whole-body removal kinetics of
sorbitol, the use of extrarenal sorbitol clearance to estimate hepatic plasma
flow in humans, and to compare measurements of liver flow by Fick's principle
using either indocyanine green (ICG) or sorbitol. A sorbitol bolus (5 mmol/kg)
was given intravenously to 6 controls for determination of sorbitol elimination
capacity (SEC) and distribution volume, V(sorb)d. Sorbitol infusion (287
micromol/ min) was given to 17 liver patients and 11 controls. Extrarenal
sorbitol clearance (V(sorb)x was calculated as infusion rate (corrected for renal
excretion and accumulation in V(sorb)d) divided by arterial concentration. Liver
flow (Q(ICG)) was calculated from the ICG infusion and arterial and hepatic
venous ICG concentrations by Fick's principle. Average SEC was 73
micromol/min/kg, V(sorb)d was 0.16 L plasma per kilogram, and in vivo V(sorb)d
was 3 mmol/L. Renal sorbitol excretion rate was 0.03 to 0.31 of infusion rate.
Extrahepatic extrarenal removal was not significantly different from zero but
varied considerably. Hepatic extraction fraction of sorbitol, (E(sorb)), measured
by liver vein catheterization, was 0.35 to 1.04 (median, 0.86) in cirrhotic
patients and 0.90 to 0.98 (0.86) in controls. The requirements for using
Cl(sorb)x as an estimate of Q(ICG) was not violated by the data in controls,
Cl(sorb)x/Q(ICG) 0.70 to 1.55 [median, 1.08]), whereas there was a systematic
underestimation in cirrhotic patients (0.72-1.08 [0.85]). Liver flow calculated
by Fick's principle using either sorbitol or ICG agreed well. E(sorb) > E(ICG) in
each individual except one. Curvilinear relationship between E(sorb) and E(ICG)
was in agreement with different kinetic parameters for sorbitol and ICG, and did
not require additional assumption of intrahepatic shunts.
PMID- 9657097
TI - A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in
vivo growth of murine and human hepatoma: implication for immunotherapy of human
hepatocellular carcinoma.
AB - Although treatment for hepatocellular carcinoma (HCC) has recently improved, most
patients still relapse and die from this disease. The development of new
therapeutic and preventive strategies for HCC is, therefore, required. A novel
mutant protein (mutein) of human tumor necrosis factor alfa (TNF-alpha mutein
F4614, 1SSSRGDSD... 29V ... 155L) was developed to decrease several adverse
effects of TNF-alpha. F4614 is known to lack hypotensive effects of human TNF
alpha without losing its anti-tumor effect in mice transplanted with Meth-A
sarcoma. Our study investigated the anti-tumor effects of F4614 against hepatoma
cells in vitro and in vivo. F4614 significantly inhibited growth of all four
tumor cells in vitro. A murine hepatoma cell line, MH134, when incubated in the
presence of F4614, exhibited upregulation of surface major histocompatibility
complex (MHC) class-I, intercellular adhesion molecule-1 (ICAM-1) and B7-1
molecules, and a decreased proportion of cells in the G2/M phase of the cell
cycle. In addition, F4614 induced apoptosis in a significant number of MH134
cells. TNF-alpha and F4614 (5 microg/mouse daily for 5 days) showed similar anti
tumor activities in syngeneic MH134-bearing mice and heterogeneic PLC/PRF/5
bearing athymic nude mice. Intratumoral injection of F4614 or TNF-alpha was more
effective than intravenous injection. Immunohistochemical analysis of the tumors
treated by F4614 revealed that tumors were surrounded with a large number of Mac
1+ cells and a small number of CD4+ and CD8+ T cells; that suggests that
intratumoral injection of F4614 elicited host immunoreactions. Thus, F4614 may be
a new strategy for immunotherapy of HCC.
PMID- 9657098
TI - Expression of vascular endothelial growth factor in human hepatocellular
carcinoma.
AB - Vascular endothelial growth factor (VEGF) is thought to take an important role in
tumor angiogenesis. The present study examined VEGF expression
immunohistochemically in hepatocellular carcinomas (HCCs) in various histological
grades and sizes. In HCCs that were composed of cancerous tissues of single
histological grade, VEGF expression was the highest in well-differentiated HCCs,
followed by moderately differentiated HCCs, and then poorly differentiated HCCs.
VEGF positivity gradually decreased with the increase in tumor size. In the
nodules larger than 3.0 cm, 36.8% were VEGF-negative. In HCCs consisting of
cancerous tissues of two different histological grades, the expression was less
intensive in the higher-grade HCC component. VEGF was not expressed in
sarcomatous areas, while VEGF was expressed in the surrounding HCC tissues. The
expression was also remarkable in the noncancerous tissues in which inflammatory
cell infiltration was apparent. VEGF expression was also examined in six HCC cell
lines. In reverse-transcription polymerase chain reaction (RT-PCR) analysis,
expressions of the two secretion types (VEGF121 and VEGF165) were the highest.
Thus, VEGF protein in culture supernatant was measured by using enzyme-linked
immunosorbent assay (ELISA) with or without inflammatory cytokines, i.e.,
interleukin (IL)-1beta, interferon (IFN)-alpha, IFN-gamma, and tumor necrosis
factor (TNF)-alpha; and growth factors, i.e., epidermal growth factor (EGF),
platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor (bFGF),
and transforming growth factor (TGF)-alpha. As a result, secretion of VEGF from
the cell lines was upregulated at various degrees. Based on these findings, VEGF
expression in HCC tissues was thought to be related to the histological grade.
The findings also indicate that various cytokines and growth factors could
cooperatively act to enhance VEGF expressions in HCC.
PMID- 9657099
TI - Genomic fluidity is a necessary event preceding the acquisition of tumorigenicity
during spontaneous neoplastic transformation of WB-F344 rat liver epithelial
cells.
AB - The genomic evolution of a cohort of WB-F344 rat liver epithelial cell lineages
undergoing spontaneous neoplastic transformation was followed to define the
mechanistic relationship between genomic instability and progression to the
neoplastic phenotype. Eighteen independent populations of WB-F344 cells
(initiated from a single diploid-founding population) were subjected to 12 cycles
of selective growth at confluent cell density, and cellular DNA contents were
measured after each selection cycle. Flow cytometry demonstrated significant
gains in the amount of G1 DNA after selection cycles 3, 6, and 7 in 44% (8 of
18), 89% (16 of 18), and 39% (7 of 18) of the cell populations, respectively. All
populations subsequently lost DNA and returned to a diploid or pseudo-diploid DNA
content within 1 to 2 selection cycles after the appearance of an increased DNA
content. Additionally, appearance and subsequent disappearance of aneuploid or
tetraploid subpopulations was observed in 11% (2 of 18) and 83% (15 of 18) of the
experimental lineages, respectively. Although perturbations of G1 DNA content
were apparent as early as selection cycle 3, at least 8 cycles of selective
growth were required for the acquisition of tumorigenicity. While the independent
lineages demonstrated significant fluctuations in G1 DNA content between
selection cycles 3 and 8, the majority (11 of 13) of the populations contained a
diploid or pseudo-diploid DNA content at the time tumorigenicity was expressed.
Genomic instability preceded the acquisition of tumorigenic potential in rat
liver epithelial cells subjected to selective growth conditions of maintenance at
confluence, and may be required for its expression.
PMID- 9657100
TI - Allelic imbalance of insulin-like growth factor II gene expression in cancerous
and precancerous lesions of the liver.
AB - Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression
is often seen in hepatocellular carcinoma (HCC). To investigate the role of
allelic imbalance in hepatocarcinogenesis, we have studied allelic expression
status of the IGF II gene in dysplastic nodules, which are precancerous lesions
of HCC, as well as in HCCs of different histological grade, and the influence of
the allelic imbalance on IGF II gene expression has also been examined. Allelic
imbalance was observed in 3 of 7 dysplastic nodules, in 7 of 9 well
differentiated HCCs, and in 8 of 9 moderately differentiated HCCs. IGF II gene
expression level, which was studied by a semiquantitative reverse-transcriptase
polymerase chain reaction (RT-PCR), was significantly higher (3.6-fold) in the
dysplastic nodules than the control livers, but a significant increase in the IGF
II gene expression was not observed in well- and moderately differentiated HCCs
as compared with the control livers. These results demonstrate that the allelic
imbalance of the IGF II gene expression is seen in the early stage (precancerous
lesions) of hepatocarcinogenesis. Association of the allelic imbalance with an
increased expression of the IGF II gene in the precancerous lesions might suggest
a possible involvement of an IGF II autocrine loop in the pathogenesis of these
lesions.
PMID- 9657101
TI - Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene
loci occurs during hepatic carcinogenesis.
AB - DNA mismatch repair is an important mechanism involved in maintaining the
fidelity of genomic DNA. Defective DNA mismatch repair is implicated in a variety
of gastrointestinal and other tumors; however, its role in hepatocellular
carcinoma (HCC) has not been assessed. Formalin-fixed, paraffin-embedded archival
pathology tissues from 46 primary liver tumors were studied by microdissection
and microsatellite analysis of extracted DNA to assess the degree of
microsatellite instability, a marker of defective mismatch repair, and to
determine the extent and timing of allelic loss of two DNA mismatch repair genes,
human Mut S homologue-2 (hMSH2) and human Mut L homologue-1 (hMLH1), and the
tumor suppressor genes adenomatous polyposis coli gene (APC), p53, and DPC4.
Microsatellite instability was detected in 16 of the tumors (34.8%). Loss of
heterozygosity at microsatellites linked to the DNA mismatch repair genes, hMSH2
and/or hMLH1, was found in 9 cases (19.6%), usually in association with
microsatellite instability. Importantly, the pattern of allelic loss was uniform
in 8 of these 9 tumors, suggesting that clonal loss had occurred. Moreover, loss
at these loci also occurred in nonmalignant tissue adjacent to 4 of these tumors,
where it was associated with marked allelic heterogeneity. There was relatively
infrequent loss of APC, p53, or DPC4 loci that appeared unrelated to loss of
hMSH2 or hMLH1 gene loci. Loss of heterozygosity at hMSH2 and/or hMLH1 gene loci,
and the associated microsatellite instability in premalignant hepatic tissues
suggests a possible causal role in hepatic carcinogenesis in a subset of
hepatomas.
PMID- 9657102
TI - Collagen XVIII is localized in sinusoids and basement membrane zones and
expressed by hepatocytes and activated stellate cells in fibrotic human liver.
AB - Type XVIII collagen is a recently discovered nonfibrillar collagen associated
with basement membranes in mice and expressed at high levels in human liver. We
studied the origin, distribution, and RNA levels of type XVIII collagen in normal
and fibrotic human livers by in situ hybridization, immunohistochemistry, and
Northern and dot blots and compared procollagen alpha1(XVIII) RNA levels with
those of procollagen alpha1(IV) and laminin gamma1, the two major components of
liver basement membranes. In normal liver, type XVIII collagen was heavily
deposited in perisinusoidal spaces and basement membrane zones. The major source
of type XVIII collagen was hepatocytes and, to a lesser extent, endothelial,
biliary epithelial, and vascular smooth muscle cells and peripheral nerves. In
cirrhosis, type XVIII collagen formed a thick deposit along capillarized
sinusoids. Grain counts after in situ hybridization showed myofibroblasts to
increase their expression 13-fold in active and twofold in quiescent fibrosis,
whereas hepatocytes increased their expression only twofold in both active and
quiescent fibrosis. Activated stellate cells in vitro expressed type XVIII
collagen at high levels. These data indicate that type XVIII collagen is a
component of the perisinusoidal space and is associated with basement membrane
remodeling. Hepatocytes and activated stellate cells are important sources of
type XVIII collagen in normal and fibrotic liver respectively, which suggests
tissue-specific regulation of its expression.
PMID- 9657103
TI - Interleukin-8 and hIRH (SDF1-alpha/PBSF) mRNA expression and histological
activity index in patients with chronic hepatitis C.
AB - Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell-derived
factor 1 (SDF1-alpha)/pre-B-cell growth-stimulating factor (PBSF), a new
chemokine, exhibits an in vitro chemotaxis to neutrophils and a mixed in vivo
chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat
intradermal injection model. We have investigated the messenger RNA (mRNA)
expression of interleukin-8 (IL-8) and hIRH, in chronic hepatitis C of differing
severity. Levels of expression of IL-8 and hIRH mRNA obtained from 37 human liver
biopsy samples were measured by reverse-transcription and semiquantitative
polymerase chain reaction (RT-PCR) amplification. We examined the correlation
between mRNA expression and components of the histological activity index (HAI).
Patients with HAI > or = 8 had a significantly higher corrected IL-8 mRNA
expression ratio (0.24 +/- 0.13 [mean +/- SD]; n = 20) than those with HAI < or =
7 (0.05 < or = 0.03; n = 17; P < .0001). Additionally, IL-8 mRNA expression was
strongly associated with the severity of portal inflammation (PI) (high PI vs.
low PI, 0.22 +/- 0.14 vs. 0.05 +/- 0.04; P < .0001) and with the presence of bile
duct lesions (0.29 +/- 0.15 vs. 0.11 +/- 0.1; P < .01). In contrast, hIRH mRNA
expression was not associated with the total HAI, any components of the HAI, or
bile duct inflammation or injury. These results suggest that hIRH, although
having the -CXC-, alpha chemokine motif, and exhibiting in vivo and in vitro
inflammatory activity as does IL-8, plays a different role from IL-8 in hepatic
inflammation and injury. IL-8 expression is directly associated with inflammation
in patients with chronic hepatitis C, while hIRH expression does not correlate
with histopathological severity of inflammation.
PMID- 9657104
TI - Protein phosphatase inhibition in normal and keratin 8/18 assembly-incompetent
mouse strains supports a functional role of keratin intermediate filaments in
preserving hepatocyte integrity.
AB - The function and regulation of keratin 8 (K8) and 18 (K18), intermediate filament
(IF) proteins of the liver, are not fully understood. We employed the liver
damage induced by microcystin-LR (MC-LR), a liver-specific inhibitor of type-1
and type-2A protein phosphatases, in normal and in keratin assembly-incompetent
mouse strains as a model to elucidate the roles of IF phosphorylation in situ.
The mouse strains used were wild-type (wt) mice and mice with abnormal filament
assembly, caused by a targeted null mutation of the K8 gene or caused by
expression of a point-mutated dominant negative human K18. In vivo 32P-labeled wt
mice, subsequently injected with a lethal dose of MC-LR, showed
hyperphosphorylation, disassembly, and reorganization of K8/K18, in particular
K18, indicating high phosphate turnover on liver keratins in situ. At lethal
doses, the keratin assembly-incompetent mice displayed liver lesions faster than
wt mice, as indicated histopathologically and by liver-specific plasma enzyme
elevations. The histological changes included centrilobular hemorrhage in all
mouse strains. The assembly-incompetent mice showed a marked vacuolization of
periportal hepatocytes. Indistinguishable MC-LR-induced reorganization of
microfilaments was observed in all mice, indicating that this effect on
microfilaments is not dependent on the presence of functional K8/K18 networks. At
sublethal doses of MC-LR, all animals had the same potential to recover from the
liver damage. Our study shows that K8/K18 filament assembly is regulated in vivo
by serine phosphorylation. The absence or occurrence of defective K8/K18
filaments render animals more prone to liver damage, which supports the
previously suggested roles of keratin IFs in maintenance of structural integrity.
PMID- 9657105
TI - Effects of diosgenin, a plant-derived steroid, on bile secretion and
hepatocellular cholestasis induced by estrogens in the rat.
AB - Increased biliary secretion of cholesterol and lipid vesicles (unilamellae and
multilamellae) induced by diosgenin (D), a plant-derived steroid, has
cytoprotective effects in the rat liver subjected to obstructive cholestasis. In
this study, our aims were to investigate the following: 1) the effects of D on
the bile secretory process and on the cholestasis induced by estradiol-17beta
(beta-D-glucuronide) (E17G) or 17 alpha-ethynylestradiol (E) administration; 2)
whether the potentially protective effects of D are related to D-induced increase
of biliary cholesterol and lipid lamellae; and 3) whether D has other effects
capable of modifying specific bile secretory processes or preventing the
cholestatic effects of estrogens. Rats were fed a standard ground chow (control
group) or chow containing D for 6 days. E17G was administered i.v. to control and
D-fed rats and bile flow, bile salt output, and alkaline phosphatase excretion
were examined. 17alpha-E was administered from days 4 to 6 to rats fed standard
chow or chow plus D for 6 days and different functional parameters of the bile
secretory process as well as the ultrastructure of hepatocytes and histochemistry
of alkaline phosphatase and Mg2+-adenosine triphosphatase (ATPase) were examined.
D-treatment markedly increased cholesterol and lamellar structures in bile and
attenuated the acute cholestatic effects of E17G. D-feeding prevented the
decrease of taurocholate maximum secretory rate and the increase of biliary
alkaline phosphatase and Ca2+,Mg2+-EctoATPase (EctoATPase) excretion, as well as
the increase of cholesterol/ phospholipids ratio, alkaline phosphatase activity,
and EctoATPase content in canalicular plasma membranes induced by E. D-feeding
did not prevent E-induced decrease of basal bile flow, bile salt, cholesterol,
and phospholipid secretory rates nor the decrease of Na+,K+-ATPase activity and
Na+-taurocholate cotransporting polypeptide (Ntcp) content in isolated sinusoidal
membranes. Cholestatic alterations of canalicular domain were apparent in E
treated rats. D administration was also associated with changes of ultrastructure
and histochemistry of hepatocytes. E-induced alterations in ultrastructure and
acinar distribution and intensity of histochemical reaction of both enzymes were
partially prevented by D-feeding. We conclude that D administration, in addition
to inducing a marked increase of biliary cholesterol and lipid lamellar
structures output, was associated to changes in hepatocyte morphology and plasma
membrane composition, enzymes activity, and histochemistry. D-feeding attenuated
the acute cholestatic effects of E17G. D-induced increase of bile cholesterol and
lipid lamellae content was not apparent when D-fed rats received E. Despite this
fact, D administration prevented some cholestatic effects of E, probably through
different metabolic effects and/or direct membrane effects, not related to
increased lipid lamellae excretion.
PMID- 9657106
TI - Insulin resistance in cirrhosis: prolonged reduction of hyperinsulinemia
normalizes insulin sensitivity.
AB - Insulin resistance is present in nearly all patients with cirrhosis, but its
etiology remains unknown. Chronic hyperinsulinemia has been suspected as a
potential candidate, and we therefore tested the hypothesis that, in cirrhosis,
prolonged reduction of the hyperinsulinemia restores insulin sensitivity. Whole
body insulin sensitivity (euglycemic insulin-clamp technique), glucose turnover
(6,6-2H2-glucose isotope dilution), glucose oxidation (indirect calorimetry), non
oxidative glucose disposal, and fractional glycogen synthase activity in muscle
(biopsies) were measured in eight clinically stable patients with cirrhosis
before and at the end of a 4-day continuous subcutaneous infusion of the
somatostatin-analogue octreotide (200 microg/24 h) designed to continuously
reduce plasma insulin levels. Baseline data were compared with results obtained
in healthy individuals matched for sex, age, and weight (n = 8). During the
baseline (pre-octreotide) study, patients demonstrated a significant decrease in
insulin-mediated glucose uptake compared with controls (5.75 +/- 0.21 vs. 7.98 +/
0.84 mg/kg/min; P < .03), which was entirely accounted for by an impairment in
non-oxidative glucose disposal (P < .04). Four-day infusion of octreotide to
cirrhotic patients: 1) reduced postabsorptive and meal-stimulated plasma insulin
levels by approximately 35% to 45% without significantly affecting glucose
tolerance; 2) did not significantly alter plasma free fatty acids (FFA), growth
hormone, and glucagon levels in the postabsorptive state and during the meal
test; 3) normalized insulin-mediated whole-body glucose disposal (7.63 +/- 0.72
mg/kg/min post-octreotide; P = not significant vs. control). Restoration of
insulin-mediated glucose utilization was entirely caused by normalization of non
oxidative glucose disposal; 4) was associated with a considerably more pronounced
stimulation by insulin of the fractional glycogen synthase in muscle compared
with pre-octreotide results (increment above baseline pre: 0.035 +/- 0.010 vs.
post: 0.060 +/- 0.023 nmol/min/mg protein; P < .04). Fractional glycogen activity
significantly correlated with non-oxidative glucose disposal during insulin
infusion (r = .69; P < .03). Prolonged reduction of hyperinsulinemia for 96 hours
in cirrhotic patients normalizes insulin-mediated glucose uptake and glycogen
synthesis in muscle. We conclude that chronic hyperinsulinemia causes insulin
resistance in cirrhosis.
PMID- 9657107
TI - Initial heme uptake from albumin by short-term cultured rat hepatocytes is
mediated by a transport mechanism differing from that of other organic anions.
AB - Although it is known that circulating heme accumulates in liver cells, the
process by which heme enters hepatocytes is only partly understood. Hemopexin and
a putative hemopexin receptor on hepatocyte membranes may mediate the uptake
process. However, whether there are sufficient hemopexin receptors on rat
hepatocytes to account for the bulk of heme entering cells is unknown. It is
likely that heme may be transferred directly from albumin with the help of a
plasma membrane heme transporter. To clarify the transport mechanism of heme into
liver cells, we studied the uptake by short-term cultured rat hepatocytes of 55Fe
heme incubated with rat serum albumin. In these cells, the initial uptake of 55Fe
heme at 37 degrees C was five- to eightfold higher than that at 4 degrees C,
linear for at least 5 minutes, and saturable. The Km of heme uptake was 0.95 +/-
0.27 micromol/L, and the Vmax was 0.12 +/- 0.01 pmol/min/mg protein (n = 3).
Neither isosmotic substitution of sucrose for NaCl in the medium nor adenosine
triphosphate (ATP) depletion, perturbations that are known to reduce uptake of
bilirubin, sulfobromophthalein (BSP), and taurocholate, had any influence on 55Fe
heme uptake. In addition, heme uptake was not reduced in the presence of a
greater than 500-fold molar excess of BSP. These results indicate that
hepatocytes take up heme by a process that is distinct from that of these other
organic anions.
PMID- 9657109
TI - The polarized hepatic human/rat hybrid WIF 12-1 and WIF-B cells communicate
efficiently in vitro via connexin 32-constituted gap junctions.
AB - Gap junction intercellular communication (GJIC) plays an essential role in the
control of growth, differentiation, and functions of different tissues. The
expression of connexins (Cxs), the structural proteins of gap junctions, is
developmentally regulated and tissue-specific. In vivo hepatocytes express Cx32
and Cx26. Most currently available in vitro hepatic cell systems express Cx43
instead of the expected Cxs. This work analyzes the GJIC competence and Cx
expression of the highly differentiated and polarized hepatoma-derived hybrid
cell lines, WIF 12-1 and WIF-B. It shows (using two dye transfer assays) that
both lines communicate efficiently and that the acquisition of GJIC competence
precedes the formation of bile canaliculi. Interestingly, these cells communicate
via Cx32 expression, whereas Cx26 and Cx43 are not expressed, as demonstrated by
Western and Northern blotting, immunocytochemistry, and confocal microscopy. The
human fibroblast W138 parent communicates via Cx43, whereas the rat hepatoma
parent Fao and the subclone WIF 12-1 TGdelta, that has lost the human X
chromosome, do not communicate, the expression of Cx32 being restricted to the
mRNA in these two lines. The GJIC competence of WIF cells could thus result from
the activation of the human X chromosome-linked Cx32 gene.
PMID- 9657108
TI - Expression of cytosolic beta-glucosidase in guinea pig liver cells.
AB - The cytosolic beta-glucosidase of mammalian liver has been implicated in the
metabolic transformation of plant glycosides, such as vicine and amygdalin, which
are associated with the development of toxic syndromes. We investigated which
cell types express cytosolic beta-glucosidase in guinea pig liver, and
characterized the contribution of this enzyme to the hydrolysis of aromatic
glucosides in cultured cells and in tissue slices. Cytosolic beta-glucosidase was
expressed in hepatocytes and not in Kupffer or endothelial cells as determined by
enzyme-specific activity and Western blots of liver cell extracts. Intracellular
beta-glucosidase activity was visualized using the fluorescent beta-glucosidase
substrate, resorufin beta-D-glucoside, and shown to be caused by the cytosolic
beta-glucosidase using the inhibitors, conduritol beta-epoxide and dinitrophenol
2-deoxy-2-fluoro-beta-D-glucopyranoside (DNP2FGlc). Staining of fresh liver
slices with resorufin beta-glucoside revealed that cytosolic beta-glucosidase is
expressed in all hepatocytes, with no significant portal-central gradient. These
data indicate that cytosolic beta-glucosidase is a hepatocyte-specific enzyme,
and support the hypothesis that cytosolic beta-glucosidase in the liver functions
to hydrolyze small glucosides absorbed by the intestine. Furthermore, toxic
injury to cultured hepatocytes by CCl4 resulted in release of cytosolic beta
glucosidase in parallel with the hepatocyte marker enzymes alanine transaminase
and lactate dehydrogenase. This suggests that acute increases in serum levels of
cytosolic beta-glucosidase in animal models of liver injury may reflect direct
injury of hepatocytes.
PMID- 9657110
TI - Lack of coordinate control of ferritin and transferrin receptor expression during
rat liver regeneration.
AB - Transferrin receptor (TfR) and ferritin, key proteins of cellular iron
metabolism, are coordinately and divergently controlled by cytoplasmic proteins
(iron regulatory proteins, IRP-1 and IRP-2) that bind to conserved mRNA motifs
called iron-responsive elements (IRE). IRP, in response to specific stimuli (low
iron levels, growth and stress signals) are activated and prevent TfR mRNA
degradation and ferritin mRNA translation by hindering ferritin mRNA binding to
polysomes. We previously found that, in regenerating liver, IRP activation was
accompanied by increased TfR mRNA levels, but not by reduced ferritin expression.
The basis for this unexpected behavior was investigated in the present study.
Liver regeneration triggered by carbon tetrachloride (CCl4) stimulated by four-
to fivefold the synthesis of both L and H ferritin chains. This increase was
accompanied with a transcriptionally regulated twofold rise in the amount of
ferritin mRNAs. Moreover, polysome-associated ferritin transcripts were fourfold
higher in CCl4-treated animals than in control animals. Because RNA bandshift
assays showed a fourfold increase in IRP-2 binding activity after CCl4
administration, activated IRP in regenerating liver seemed unable to prevent
ferritin mRNAs binding to polysomes. This was confirmed by direct demonstration
in the wheat germ translation system that the efficiency of IRP as a
translational repressor of a mRNA bearing an IRE motif in front of a reporter
transcript is impaired in CCl4-treated rats in spite of an enhanced IRE-binding
capacity. In conclusion, we show for the first time that the paradigm of
coordinate and opposite control of ferritin and TfR by IRP is contradicted in
liver regeneration. Under these circumstances, growth-dependent signals may
activate ferritin gene transcription and at the same time hamper the ability of
activated IRP-2 to repress translation of ferritin mRNAs, thus preserving for
growing liver cells an essential iron-storage compartment.
PMID- 9657111
TI - Antiviral activity and toxicity of fialuridine in the woodchuck model of
hepatitis B virus infection.
AB - Woodchucks were used to study the antiviral activity and toxicity of fialuridine
(FIAU; 1,-2'deoxy-2'fluoro-1-beta-D-arabinofuranosyl-5-iodo-uracil). In an
initial experiment, groups of six chronic woodchuck hepatitis virus (WHV) carrier
woodchucks received daily doses of FIAU by intraperitoneal injection for 4 weeks.
At 0.3 mg/kg/d, the antiviral effect was equivocal, but at 1.5 mg/kg/d, FIAU had
significant antiviral activity. No evidence of drug toxicity was observed during
the 4-week period of treatment or during posttreatment follow-up. In a second
experiment, groups of nine WHV carriers or uninfected woodchucks were given 1.5
mg/kg/d of FIAU orally for 12 weeks, and the results compared with placebo
treated controls. After 4 weeks, the serum WHV-DNA concentration in the FIAU
treated carrier group was two to three logs lower than that in the placebo
treated group. After 12 weeks of FIAU treatment, serum WHV DNA was not detectable
by conventional dot-blot analysis, hepatic WHV-DNA replicative intermediates (RI)
had decreased 100-fold, and hepatic expression of WHV core antigen was remarkably
decreased. No evidence of toxicity was observed after 4 weeks, but, after 6 to 7
weeks, food intake decreased and, after 8 weeks, the mean body weights of
woodchucks treated with FIAU were significantly lower than controls. Anorexia,
weight loss, muscle wasting, and lethargy became progressively severe, and all
FIAU-treated woodchucks died or were euthanized 78 to 111 days after treatment
began. Hepatic insufficiency (hyperbilirubinemia, decreased serum fibrinogen,
elevated prothrombin time), lactic acidosis, and hepatic steatosis were
characteristic findings in the final stages of FIAU toxicity in woodchucks. The
syndrome of delayed toxicity in woodchucks was similar to that observed
previously in humans treated with FIAU, suggesting that the woodchuck should be
valuable in future investigations of the molecular mechanisms of FIAU toxicity in
vivo and for preclinical toxicological evaluation of other nucleoside analogs
before use in patients.
PMID- 9657112
TI - Continuous human cell lines inducibly expressing hepatitis C virus structural and
nonstructural proteins.
AB - Investigation of the hepatitis C virus (HCV) life cycle and the evaluation of
novel antiviral strategies are limited by the lack of an efficient cell culture
system. Therefore, continuous human cell lines inducibly expressing the entire
HCV open reading frame were generated with use of a tetracycline-regulated gene
expression system. HCV transgenes were found to be chromosomally integrated in a
head-to-tail configuration. Northern blot analyses revealed a tightly regulated
unspliced transcript of approximately 9 kilobases (kb). HCV structural and
nonstructural proteins were faithfully processed, indicating that the cellular
and viral proteolytic machineries and posttranslational modification pathways are
fully functional in these cell lines. Steady state expression levels could be
regulated over a broad range by the concentration of tetracycline present in the
culture medium. Kinetic analyses revealed a half-life of less than 1 hour for the
HCV RNA whereas a half-life of approximately 9.5, 12, 11, and 10 hours was found
for core, NS3, NS4A, and NS5A proteins, respectively. Viral proteins were found
to colocalize in the cytoplasm in a pattern characteristic of the endoplasmic
reticulum. High-level expression of HCV proteins in the fully induced state was
toxic to the cells. These cell lines provide a unique in vitro system to analyze
structural and functional properties of HCV proteins, their interactions with
cellular proteins and pathways, and the requirements for HCV morphogenesis. In
addition, they should prove useful for the evaluation of novel antiviral
strategies against hepatitis C in a well-defined and reproducible cellular
context.
PMID- 9657113
TI - Cytokine and hepatitis B virus DNA co-immunizations enhance cellular and humoral
immune responses to the middle but not to the large hepatitis B virus surface
antigen in mice.
AB - Genetic immunization is a potentially useful strategy to prevent or treat
hepatitis B virus (HBV) infection. We have previously shown that HBV envelope
proteins are highly immunogenic using this technique. The large envelope protein
(LHBs), however, induced significantly weaker humoral and cellular immune
responses when compared with the middle envelope protein (MHBs). We studied the
effect of co-immunizations with cytokine DNA expression constructs encoding for
interleukin (IL)-2 and (GM-CSF) on the immunogenicity of LHBs at the B-and T-cell
level. Co-immunizations of mice with plasmids encoding for MHBs and IL-2 or GM
CSF increased anti-HBs responses, helper T-cell proliferative activity, and
cytotoxic T lymphocyte (CTL) killing. In contrast, co-immunizations of plasmids
encoding for LHBs and IL-2 or GM-CSF had no effect on humoral and cellular immune
responses. LHBs did not inhibit the production or secretion of IL-2 and GM-CSF.
In addition, IL-2, tumor necrosis factor alfa (TNF-alpha), and interferon gamma
(IFN-gamma) had no suppressive effect on HBV envelope protein expression in
vitro. Based on these data, MHBs, but not LHBs, genetic immunization can be
augmented by IL-2 or GM-CSF cytokines.
PMID- 9657114
TI - Hepatitis C virus persistence in human hematopoietic cells injected into SCID
mice.
AB - The issue of infection of peripheral blood mononuclear cells (PBMC) by the
hepatitis C virus (HCV) has potentially important implications, but is still
debated. We have used the severe combined immunodeficiency (SCID) mouse model to
test for the persistence of HCV in PBMC. Hematopoietic cells isolated from 14
subjects infected by HCV were inoculated intraperitoneally into SCID mice. Serum
and blood cell samples from these mice were obtained with a mean follow-up of 8
weeks. As controls, human fibroblasts and sheep PBMC, preincubated with a human
HCV-positive serum, were inoculated concomitantly into mice and analyzed. HCV-RNA
positive strands were detected in 7 of 26 serum samples and 8 of 26 cell
fractions from SCID mice inoculated with HCV-positive PBMC, after 8 weeks of
follow-up. In contrast, no HCV RNA was detectable in the 10 control mice. HCV-RNA
negative strands were detected in only 2 of 10 tested samples from 2 mice, and
both positive mice had been inoculated with PBMC from HCV-positive subjects with
malignant hematopoietic syndrome. Our study offers strong evidence for the
persistence of HCV infection in mononuclear cells. Our results are also
consistent with a low rate of HCV multiplication. This SCID mouse model might
therefore be useful in analyzing the mechanisms of HCV persistence in mononuclear
cells.
PMID- 9657115
TI - Human and murine antibody recognition is focused on the ATPase/helicase, but not
the protease domain of the hepatitis C virus nonstructural 3 protein.
AB - The hepatitis C virus (HCV) nonstructural (NS) 3 protein has been shown to
possess at least two enzymatic domains. The amino terminal third contains a
serine-protease domain, whereas the carboxy terminal two thirds is comprised of
an adenosine triphosphatase (ATPase)/helicase domain. These domains are essential
for the maturation of the carboxy-terminal portion of the HCV polyprotein and
catalyze the cap synthesis of the RNA genome. In this report, human and murine
antibody responses induced by NS3 were characterized using a recombinant full
length NS3 (NS3-FL) protein, or the isolated protease or ATPase/ helicase
domains, expressed and purified from Escherichia coli. Sera from 40 patients with
chronic HCV infection were assayed in enzyme-linked immunoassays (EIAs) for
antibody binding to the panel of NS3 proteins. Virtually all patient sera
contained antibodies specific for NS3-FL and the ATPase/helicase domain, whereas
only 10% of sera reacted with the protease domain of NS3. Human antibodies
reactive with NS3-FL were highly restricted to the immunoglobulin G1 (IgG1)
isotype and were inhibited by soluble ATPase/helicase, but not by the protease
domain. The anti-NS3 (ATPase/helicase) reactivity decreased on denaturation by
sodium dodecyl sulfate (SDS) and beta-mercaptoethanol (2ME), suggesting the
recognition of nonlinear or conformational B-cell determinants. Similar to
infected humans, mice immunized with NS3-FL developed high-titered primary
antibody responses to the NS3 ATPase/ helicase domain, whereas an anti-NS3
protease response was not observed after primary or secondary immunizations.
Thus, the human and murine humoral immune responses to the HCV NS3 protein are
focused on the ATPase/helicase domain, are restricted to the IgG1 isotype in
humans, and are conformationally dependent. Unexpectedly, in both species, the
NS3 protease domain, present in the context of the full-length NS3, appears to
possess low intrinsic immunogenicity in terms of antibody production.
PMID- 9657116
TI - Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and
response to interferon alfa therapy in chronic hepatitis C.
AB - Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) have been shown to
play a role in host defense and pathogenesis of chronic HCV infection. Our aim
was to test the hypothesis that intrahepatic HCV-specific CTL activity may impact
subsequent response to interferon alfa (IFN-alpha) therapy. Of the 37 patients
that we have prospectively evaluated for HCV-specific CTL activity in liver, 21
received IFN therapy, and 19 completed a 6-month course and attended 6 to 18
months of follow-up. Intrahepatic CD8+ cells were isolated from liver biopsy
tissue and tested against target cells expressing HCV antigens to determine
intrahepatic CTL activity. The relationship between treatment response and HCV
specific CTL activity and other factors known to associate with response
(genotype, viremia, histology) was analyzed. HCV-specific CTL activity was
detected in 9 of 21 patients (and 9 of 19 who completed therapy). After 6 months
of IFN therapy, 8 of 19 (42%) patients had normal serum alanine transaminase
(ALT) (complete responders). After 18 months of follow-up, only 3 patients (16%)
had a sustained biochemical response. Of the 9 patients with detectable HCV
specific CTL activity in their liver before treatment, 7 (78%) developed a
complete response. In contrast, only 1 of the 10 patients with no detectable HCV
specific CTL activity developed a complete response to IFN (P < .01). In 6 of 8
patients with a complete response, including the 3 sustained responders, the CTL
response appeared to be directed predominately to the HCV core region. These data
suggest that the host immune response, particularly that mediated by CD8+ CTL,
may be important in determining the outcome of IFN therapy for chronic HCV
infection. Further understanding of the mechanism of action of IFN should impact
the design of better therapeutic strategies against chronic HCV infection.
PMID- 9657117
TI - Sero-clearance of hepatitis B surface antigen in chronic carriers does not
necessarily imply a good prognosis.
AB - The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the
natural history of chronic hepatitis B virus (HBV)-infected patients was low.
Previous studies regarding the prognosis in such patients were controversial.
Among 1,355 chronic carriers from 1985 to 1997, spontaneous HBsAg clearance was
observed in 55 patients. During a mean follow-up period of 23 months, 18 (32.7%;
all were male subjects) developed serious complications, including 11 with
hepatocellular carcinoma (HCC) (9 of them underwent surgical resection), 6 with
cirrhosis, and 1 with subfulminant liver failure. The overall cumulative
probability of complications was 29.8% at 4 years, and it was higher in males (P
= .044) and patients aged 45 years or more (P = .006); the latter carried an 8.6
fold increased risk (95% CI: 1.2-64.6; P = .037) of adverse events. Histories of
acute or chronic infection by hepatitis A virus, C virus (HCV), or D virus (HDV)
were present in 42% of patients. Patients seropositive for antibodies against HCV
(anti-HCV) or HDV (anti-HDV) had higher alanine transaminase (ALT) levels (>40
U/L; P = .008) after sero-clearance. HBV DNA was detectable in 31% of 51
subjects, in 20% of 20 with antibodies against HBsAg, in 40% of 20 with anti-HCV
or anti-HDV, and also in an HCC patient's serum and tumor. Staining of liver
HBsAg was positive in 30% of 10 HCC patients. In conclusion, our results
demonstrated that hepatitis B viremia may persist, and adverse complications were
not rare in HBsAg-clearance patients. All such patients should be closely
monitored, which may allow for earlier detection of HCC.
PMID- 9657118
TI - Modulation of immune responses to hepatitis C virus envelope E2 protein following
injection of plasmid DNA using single or combined delivery routes.
AB - Different delivery routes of plasmid DNA may result in the induction of
differential humoral and cellular immunity. We have studied the influence of two
main routes of plasmid injection, performed intramuscularly and intraepidermally
using a gene gun, for the induction of immune responses specific to hepatitis C
virus (HCV) envelope protein E2. Three plasmids expressing different immunogenic
domains of E2 (amino acids [aa] 384443, aa 504-555, and aa 384-746) were injected
into BALB/c mice according to five different protocols using various combinations
of intramuscular (i.m.) or intraepidermal (i.e.) primary and booster injections.
Seroconversion rates, antibody titers and isotypes, epitope recognition, and T
helper (Th) release cytokine profiles were analyzed. Antibody titers and epitope
recognition were linked to either or both the nature of the immunogen expressed
and the delivery route chosen. In all cases, the lowest antibody titers were
obtained using single i.m.-based protocols. Independently of the antibody titers
generated, only some specific i.e.-combined delivery routes induced antibodies
able to recognize determinants located in the N-terminal of E2 (aa 384411 and aa
411437) and mimicked by synthetic peptides. By contrast, the antibody isotypes
and the splenic cytokine production identified were independent of the plasmids
used and the delivery route implemented. All conditions resulted in Th-1 like
responses suggested by the exclusive detection of IgG2a and 2b antibodies and the
production of interferon gamma (INF-gamma) but no interleukin-4 (IL-4). Overall,
our results suggest that the combination of i.m. and i.e. delivery routes
provides the most efficient way to induce a broad immune response against HCV-E2.
PMID- 9657119
TI - Hepatitis C virus dynamics in vivo: effect of ribavirin and interferon alfa on
viral turnover.
AB - Treatment of patients with chronic hepatitis C with recombinant interferon alfa
(rIFN-alpha) can cause a decrease of serum transaminases and hepatitis C virus
(HCV) RNA. Recent trials evaluating combination therapy of IFN-alpha and
ribavirin suggested a potential synergistic effect. From serial measurements of
serum HCV RNA concentrations following treatment-induced perturbation of the
balance between virus production and clearance, we compared the antiviral
efficacy of both IFN-alpha alone and IFN-alpha in combination with ribavirin.
Chronically HCV-infected patients were treated with either 3 x 3 MU or 3 x 6 MU
rIFN-alpha per week or 3 x 6 MU rIFN-alpha plus 14 mg/kg of body weight ribavirin
per day. The time-dependent HCV RNA concentrations during antiviral treatment
were analyzed by iterative least-squares regression. After initiation of
antiviral therapy, HCV RNA declined exponentially below the detection limit of
the reverse-transcription polymerase chain reaction assay (1,000 HCV RNA
molecules per milliliter) in 10 of 26 (39%), 10 of 19 (53%), and 10 of 18
patients (56%) treated with 3 x 3 MU, 3 x 6 MU rIFN-alpha without and with
ribavirin, respectively. Viral clearance from serum was faster in patients
treated with 3 x 6 MU rIFN-alpha (t1/2 = 0.23 +/- 0.15) compared with patients
treated with 3 x 3 MU rIFN-alpha per week (0.67 +/- 0.36 days) (P < .004).
However, half-lives of viral clearance were similar in patients treated with rIFN
alpha or rIFN-alpha plus ribavirin. For virus release from infected hepatocytes,
absence and presence of ribavirin yielded half-lives of t1/2 = 2.54 +/- 2.10 and
t1/2 = 1.99 +/- 1.70, respectively, indicating that ribavirin does not
significantly inhibit HCV production. In conclusion, the data of the present
study indicate that higher rIFN-alpha doses accelerate viral clearance from
serum. Ribavirin (14 mg/kg/d), however, lacks synergistic antiviral effects in
the treatment of chronic hepatitis C with 3 x 6 MU rIFN-alpha per week.
PMID- 9657120
TI - Clinicopathology conferences: inflammation-induced cholestasis.
PMID- 9657121
TI - Does the hepatitis C virus replicate in cells of the hematopoietic lineage?
PMID- 9657122
TI - Chronic carriers of hepatitis B virus who clear hepatitis B surface antigen: are
they really "off the hook"?
PMID- 9657123
TI - Mouse genetics at work: a new model of chronic hepadnavirus infection.
PMID- 9657124
TI - Without victory there is no survival: transarterial lipiodol chemoembolization
and hepatocellular carcinoma.
PMID- 9657125
TI - Hepatitis B virus vaccines: some cryptic issues.
PMID- 9657126
TI - Detection of hepatocellular carcinoma in cirrhotic livers with lipiodol-CT.
PMID- 9657127
TI - Chronic leukemias.
PMID- 9657128
TI - The real CD34+ events: simplicity or complexity?
PMID- 9657129
TI - Expansion of the nonadherent myeloid cell population by monoclonal antibodies
against tenascin-C in murine long-term bone marrow cultures.
AB - Tenascin-C, a predominantly mesenchymal extracellular matrix protein, has a
restricted distribution in adult tissues. It has previously been shown that this
protein is expressed in the bone marrow. In this paper we show that murine
myeloid and lymphoid long-term bone marrow cultures differ in their expression of
tenascin-C splice variants. In the adherent stromal layer of myeloid cultures,
the 260-kDa polypeptide encoded by the 8-kb mRNA was the major splice variant,
whereas in the stromal layer of lymphoid cultures both the shorter 210-kDa
polypeptide encoded by the 6-kb mRNA and the 260-kDa polypeptide were abundantly
expressed. However, in both culture systems the larger 260-kDa tenascin-C
polypeptide was the major isoform secreted in the culture supernatant. This
finding is in agreement with previous reports indicating that the smaller 210-kDa
isoform is preferentially deposited in the stroma, whereas the alternatively
spliced segment in the 260-kDa tenascin-C may contain anti-adhesive domains.
Glucocorticoids in myeloid long-term bone marrow cultures and in the MC3T3-G2/PA6
cell line downregulated the expression of tenascin-C. In the present study we
observed that this was due primarily to downregulation of the 8-kb major splice
variant of the tenascin-C mRNA. We also studied the possible role of tenascin-C
in the bone marrow by using antibodies against tenascin-C in long-term bone
marrow cultures. We found that three monoclonal antibodies against the
carboxyterminal type III fibronectin repeats of tenascin-C (TNCfn 7-8) increased
the number of the non-adherent myeloid cells in myeloid long-term bone marrow
cultures. It has recently been suggested that the TNCfn 6-8 domain of tenascin-C
binds to the alpha8beta1 integrin. Using Northern blotting, we found that the
integrin alpha8 subunit was expressed in adherent cells in bone marrow cultures,
raising the possibility that tenascin-C acts in bone marrow cultures by binding
to the alpha8beta1 integrin.
PMID- 9657130
TI - Assessment of proliferative and colony-forming capacity after successive in vitro
divisions of single human CD34+ cells initially isolated in G0.
AB - Exit of primitive hematopoietic progenitor cells (HPCs) from the G0 phase of the
cell cycle in response to in vitro cytokine stimulation is a limiting step in
successful ex vivo expansion. Simultaneous DNA/RNA staining with Hoechst 33342
and pyronin Y was used to separate human bone marrow CD34+ cells residing in G0
(G0CD34+) from those cycling in G1 and S/G2+M. Compared with CD34+ cells isolated
in G1, G0CD34+ cells were characterized by a delayed response to cytokine
stimulation and were enriched for long-term hematopoietic culture-initiating
cells. We next compared the activation kinetics of individually sorted G0CD34+
cells stimulated with stem cell factor (SCF), flt3-ligand (FL), or interleukin-3
(IL-3) as single factors. In a novel clonal proliferation assay, the functional
status of cells that had remained quiescent after an initial 7-day period and of
those that had completed successive division cycles under each of these three
factors was evaluated by assessment of subsequent proliferative capacity and
maintenance of colony-forming cell precursor (pre-CFC) activity. All three
cytokines were equally able to support the survival of primitive HPCs in the
absence of cell division. Cells that did not respond to any cytokine stimulation
for 7 days retained higher proliferative and pre-CFC activities than dividing
cells. The hematopoietic function of cells that divided in response to SCF, FL,
or IL-3 decreased after each division cycle. However, G0CD34+ cells displayed a
heterogeneous response pattern to cytokine stimulation whereby SCF appeared to
have a superior ability to promote the cycling of cells with high proliferative
and pre-CFC activities. These results indicate that HPCs reside in opposing
hierarchies of hematopoietic potential and responsiveness to cytokine
stimulation. The data also begin to indicate relationships between cellular
division in response to different stimuli and maintenance of hematopoietic
function.
PMID- 9657131
TI - Effect of interleukin-12 on antitumor activity of human umbilical cord blood and
bone marrow cytotoxic cells.
AB - Interleukin (IL)-12, a natural killer (NK) cell stimulatory factor, is a
heterodimeric cytokine that is known to be a potent activator of non-major
histocompatibility complex-restricted cytotoxicity by peripheral blood-derived NK
cells. NK cells (CD3-CD16+/CD56+) represent approximately 15% of human umbilical
cord blood mononuclear cells (HUCB MNCs) and are known to be highly sensitive to
activation by IL-2. In the present study, we monitored the effect of IL-12 on the
cytotoxic activity, proliferation, and phenotypic expression of HUCB-derived
resting and IL-2-activated cytotoxic cells and compared these parameters with
those of bone marrow (BM)-derived cells. Lymphocytes were separated from HUCB by
3% gelatin sedimentation and incubated with IL-12 and/or IL-2 for 18 hours. At
effector:target ratios of 40:1 and 20:1, IL-12 (50 U/mL) significantly increased
both resting and IL-2-activated NK cell-mediated cytotoxicity in a standard 51Cr
release assay against both NK-sensitive (K562) and NK-resistant (Colo-205) cell
lines. In addition, resting and IL-2-activated cytotoxic cells derived from HUCB
exhibited superior cytolytic ability compared with BM-derived cells. This
increase was observed in resting cells as well as in those that were preincubated
with IL-12. Moreover, HUCB-derived cells were found to be more sensitive to IL-12
activation than cytotoxic cells from BM. To evaluate the involvement of accessory
cells, NK cells were purified from HUCB using immunomagnetic beads, and these
cells were found to have a lower response to treatment with IL-12 than unpurified
populations. HUCB MNCs exhibited a nonsignificant increase in proliferation after
IL-12 treatment and were better able to respond to IL-12 activation than BM MNCs.
Following an 18-hour incubation, IL-12 was able to cause upregulation of CD25 and
CD69 activation antigens, whereas no significant change in expression of CD16 and
CD56 NK cell surface antigens, CD3 on T cells, or IL-12 receptor was observed.
Similarly, IL-12 did not affect NK cell:target cell conjugation as assessed by
fluorescence-activated cell sorting. Our results indicate that HUCB-derived NK
mediated cytotoxic capabilities can be increased by IL-12, a finding that may
have clinical relevance.
PMID- 9657132
TI - Enhanced lymphoid cell recovery after bone marrow transplantation: correlation
with the presence of costimulatory antibodies in serum.
AB - We describe a patient with T cell deficiency who underwent bone marrow
transplantation (BMT) from an HLA-identical brother. The patient's white blood
cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it
rose sharply to 98x10(9) cells/L, 76% of which were mononuclear leukocytes. It
then decreased, and a second peak was observed 250 days post-BMT. Lymphocytes
from both peaks displayed a phenotype of mature T cells together with
characteristics of a constitutively activated state; that is, they 1) exhibited
high levels of tyrosine-phosphorylated T cell receptor (TCR) zeta chain, 2)
spontaneously secreted IL-2, 3) expressed activation specific cell surface
markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts
in both peaks correlated with the presence of anti-lymphocytic antibodies in the
patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from
the donor and from unrelated individuals. These antibodies were present before
BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed
that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding
could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the
appearance of the second WBC peak during that period. The patient's anti
lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro
proliferation of normal T cells suboptimally activated via the TCR. The unique
characteristics of these antibodies could explain the enhanced T cell recovery
observed post-BMT as well as the constitutive activation state of these cells.
Furthermore, such antibodies may eventually facilitate development of a
therapeutic method for inducing enhanced post-BMT recovery.
PMID- 9657133
TI - Characterization of CD34+ thymic stromal cells located in the subcapsular cortex
of the human thymus.
AB - In this paper we report that suspensions of human fetal thymocytes contain cells
that express high levels of CD34 and Thy-1. These cells were characterized with
regard to location within the thymus, phenotype, and function. Confocal laser
scan analysis of frozen sections of fetal thymus with anti-CD34 and Thy-1
antibodies revealed that the double-labeled cells were located in the
pericortical area. In addition, it was found that the CD34+Thy-1+ cells lacked
CD45 and CD50, indicating that these cells are not of hematopoietic origin; this
was confirmed by the finding that these cells could be cultured as adherent cells
in a medium with cholera toxin and dexamethasone, but failed to grow in mixtures
of hematopoietic growth factors. Further analysis indicated that most cultured
CD34+Thy-1+ cells expressed cytokeratin (CK) 14 but lacked CK 13, suggesting that
these cells are immature epithelial cells. Cultured CD34+Thy-1+ cells were able
to induce differentiation of CD1-CD34+CD3-CD4-CD8- thymic precursors into
CD4+CD8+ cells in a reaggregate culture in the absence of exogenous cytokines.
The CD4+CD8+ cells that developed in these cultures did not express CD3,
indicating that CD34+Thy-1+ thymic stromal cells are not capable of completing
full T cell differentiation of thymic hematopoietic progenitor cells.
PMID- 9657134
TI - The bone marrow stromal environment is a major factor in myeloma cell resistance
to dexamethasone.
AB - Dexamethasone (Dex), which is often used for the treatment of multiple myeloma,
produces rapid reductions in tumor mass and improvement in disease symptoms;
however, it is not curative, and drug-resistant cells eventually emerge. To
elucidate this apparent paradox, we tested the effect of the bone marrow
environment on myeloma cell response to this drug. To determine whether bone
marrow stroma provides sufficient amounts of interleukin (IL)-6 to protect
myeloma cells against the effects of Dex, we compared the production of IL-6 by
marrow stromal cells from four myeloma patients before, during, and after
exposure to 10(-7) M Dex, and found that even in the presence of this drug,
stromal cells continued to produce IL-6, albeit in reduced concentrations. We
tested the ability of stromal cells to protect myeloma cells, purified from the
bone marrow of seven patients by cell sorting on the basis of CD38 and CD45
expression, and two light-scatter parameters, from Dex-induced apoptosis. In
contrast to mature CD38+CD45- cells, which were not protected, coculture with
stroma very effectively protected immature CD38+CD45+ myeloma cells from Dex.
These data may explain the palliative efficacy of Dex treatment and provide a
rationale for combining IL-6 antagonists with Dex to overcome the IL-6-mediated
resistance of immature tumor cells.
PMID- 9657135
TI - Addition of a bone marrow "facilitating cell" population increases stem cell
derived cobblestone area formation in impaired long-term bone marrow culture
stroma.
AB - Treatment of mouse bone marrow (BM) with rabbit anti-mouse brain serum (RAMBS)
plus complement (C') depletes several cell types, including T cells and
facilitating cells (FCs), that is, cells that facilitate engraftment of sorted
allogeneic stem cells (SCs) in vivo. In the present study, treatment of BM with
RAMBS+C' resulted in the depletion of approximately half of the late cobblestone
area (CA)-forming stem cells as assayed on irradiated long-term bone marrow
culture (LTBMC) stroma. In addition, LTBMC of RAMBS+C'-treated BM produced
functionally impaired stroma with reduced ability to support CA formation by
nontreated exogenous SCs. This stromal impairment was not due to depletion of
TCRalphabeta T cells in the BM, because BM cultures from TCR alpha-chain knockout
mice supported normal numbers of exogenous CAs. Because CD8+/TCR- cells are
enriched for FCs, we tested the effect of adding these cells back to the treated
BM prior to culture. The sorted FCs alone did not produce CAs, but did improve
the ability of the impaired stroma to support late CA formation by sorted SCs.
These studies provide a new model for dissecting the roles of different cellular
components of BM in producing functional stroma that supports CA formation by
SCs, and show that the number of CAs formed depends on the "quality" of the
stroma as well as the number of SCs seeded. These findings further suggest that
CD8+/TCR- BM cells may be important for the establishment of functional stroma.
PMID- 9657136
TI - The murine stromal cell line AFT024 acts specifically on human CD34+CD38-
progenitors to maintain primitive function and immunophenotype in vitro.
AB - A stromal cell line derived from murine fetal liver (AFT024) has been
demonstrated to maintain long-term repopulating murine stem cells for up to 7
weeks in vitro. We evaluated the ability of AFT024 to maintain the
immunophenotype and function of primitive human progenitors in vitro by comparing
the cocultivation of CD34+CD38 cells on AFT024 with that on primary human stroma
(HS). We have previously reported that within the CD34+CD38- population of bone
marrow and cord blood, a highly primitive progenitor subpopulation can be
identified functionally by its ability to generate colony forming unit-cells (CFU
Cs) in extended long-term culture (ELTC), that is, beyond 60 days of stromal
cocultivation. Cocultivation of bone marrow and cord blood CD34+CD38-cells on
AFT024 produced significantly greater cell expansion (p=0.0002) and CFU-C output
(p=0.0007) during the ELTC period compared with culturing on HS. CFU-C production
continued up to 9 weeks longer on AFT024 stroma. After 3 to 4 weeks of bulk
culture on either AFT024 or HS, cells were replated in a limiting dilution to
measure the number of cobblestone area-forming cells (CAFCs) maintained on each
stroma. AFT024 maintained significantly more CAFCs than did HS (n=3, p=0.002).
Fluorescence-activated cell sorter analysis of AFT024 and HS cocultures showed
that both the frequency (p=0.018) and absolute number (p=0.027) of CD34+CD38-
cells were significantly higher in cultures on AFT024 than in those on HS (n=9).
The effects of AFT024 on preservation of primitive progenitors were not seen in
transwell (noncontact) cultures. Thus, AFT024 acts by direct contact to maintain
the phenotype and function of the most primitive and quiescent human progenitors
currently identifiable by in vitro assays.
PMID- 9657137
TI - Role of plasma and platelet von Willebrand factor in arterial thrombogenesis and
hemostasis in the pig.
AB - To evaluate the relative role of plasma and platelet von Willebrand factor (vWF)
pools in hemostasis and arterial thrombogenesis, pigs with vW disease (vWD) were
injected with vWF concentrate and/or grafted with bone marrow from a normal pig.
Hemostasis was assessed by measurement of ear immersion bleeding time, factor
VIII (FVIII) activity, and plasma and platelet vWF antigen levels. The thrombotic
process was explored at 650 s(-1) and 1600 s(-1) in an ex vivo cylindrical
perfusion chamber. Pigs with vWD exhibited a prolonged bleeding time (>30
minutes) compared with normal pigs (<5 minutes); in addition, they showed normal
platelet adhesion and thrombus formation at 650 s(-1) but profoundly reduced
platelet adhesion and thrombus formation at 1600 s(-1). Each experiment was
performed before and 3 and 24 hours after injection of vWF concentrate. In our
bleeding time study, only plasma vWF restoration induced a partial but delayed
correction (24 hours postinjection), which was correlated with the highest
measured level of FVIII activity. In the perfusion chamber model, restoration of
plasma or platelet vWF pools resulted in similar partial correction of platelet
adhesion and average thrombus size. In the perfused pigs, the maximum correction
occurred 3 hours postinjection. Platelet deposition reached normal values after
vWF concentrate was injected into a grafted pig. The present results suggest that
when both plasma and platelet vWF levels are restored in vWD pigs, bleeding time
and the thrombotic process are normalized according to different kinetics and
with differing degrees of effectiveness.
PMID- 9657138
TI - Serial bone marrow sampling for long-term follow up of human hematopoiesis in
NOD/SCID mice.
AB - The study of long-term human hematopoiesis in immunodeficient mice is greatly
facilitated by sequential bone marrow (BM) sampling in individual animals. Until
now, however, the only way to obtain these samples was by sacrificing the mice.
In this paper we describe a novel technique for obtaining BM cells by aspiration
from the femur of living mice. The technique is simple and efficient and does not
disable the animals. On average 1.6+/-1x10(6) nucleated cells can be collected
from one femur at a time, which is sufficient for flow cytometry analysis,
cytospin preparations, and polymerase chain reaction assays. The cellular
composition of the samples obtained by puncture is identical to that of BM
harvested by flushing the femur after sacrificing the animals. We present the
results of 81 punctures of the femur in Hu-NOD/SCID chimeras engrafted with
Ficoll-separated or CD34bright purified cells from human umbilical cord blood.
PMID- 9657139
TI - Yeast retrotransposons: finding a nice quiet neighborhood.
PMID- 9657140
TI - Memory and the brain: what's right and what's left?
PMID- 9657141
TI - The cadherin superfamily at the synapse: more members, more missions.
PMID- 9657142
TI - Hair today, gone tomorrow: transgenic mice with human repair deficient hair
disease.
PMID- 9657143
TI - Regulation of Drosophila neurogenesis by RNA:RNA duplexes?
PMID- 9657144
TI - A 9 A resolution X-ray crystallographic map of the large ribosomal subunit.
AB - The 50S subunit of the ribosome catalyzes the peptidyl-transferase reaction of
protein synthesis. We have generated X-ray crystallographic electron density maps
of the large ribosomal subunit from Haloarcula marismortui at various resolutions
up to 9 A using data from crystals that diffract to 3 A. Positioning a 20 A
resolution EM image of these particles in the crystal lattice produced phases
accurate enough to locate the bound heavy atoms in three derivatives using
difference Fourier maps, thus demonstrating the correctness of the EM model and
its placement in the unit cell. At 20 A resolution, the X-ray map is similar to
the EM map; however, at 9 A it reveals long, continuous, but branched features
whose shape, diameter, and right-handed twist are consistent with segments of
double-helical RNA that crisscross the subunit.
PMID- 9657145
TI - F1-ATPase is a highly efficient molecular motor that rotates with discrete 120
degree steps.
AB - A single molecule of F1-ATPase, a portion of ATP synthase, is by itself a rotary
motor in which a central gamma subunit rotates against a surrounding cylinder
made of alpha3beta3 subunits. Driven by three catalytic betas, each fueled with
ATP, gamma makes discrete 120 degree steps, occasionally stepping backward. The
work done in each step is constant over a broad range of imposed load and is
close to the free energy of hydrolysis of one ATP molecule.
PMID- 9657146
TI - LMA1 binds to vacuoles at Sec18p (NSF), transfers upon ATP hydrolysis to a t
SNARE (Vam3p) complex, and is released during fusion.
AB - Vacuole fusion requires Sec18p (NSF), Sec17p (alpha-SNAP), Ypt7p (GTP binding
protein), Vam3p (t-SNARE), Nyv1p (v-SNARE), and LMA1 (low Mr activity 1, a
heterodimer of thioredoxin and I(B)2). LMA1 requires Sec18p for saturable, high
affinity binding to vacuoles, and Sec18p "priming" ATPase requires both Sec17p
and LMA1. Either the sec18-1 mutation and deletion of I(B)2, or deletion of both
I(B)2 and p13 (an I(B)2 homolog) causes a striking synthetic vacuole
fragmentation phenotype. Upon Sec18p ATP hydrolysis, LMA1 transfers to (and
stabilizes) a Vam3p complex. LMA1 is released from vacuoles in a phosphatase
regulated reaction. This LMA1 cycle explains how priming by Sec18p is coupled to
t-SNARE stabilization and to fusion.
PMID- 9657147
TI - Developmental regulation of invariant chain proteolysis controls MHC class II
trafficking in mouse dendritic cells.
AB - Dendritic cells (DCs) developmentally regulate their capacity for antigen
presentation by controlling the transport and surface expression of MHC class II
molecules. These events reflect a developmental regulation of invariant (Ii)
chain cleavage, most likely by the cysteine protease cathepsin S. In immature
DCs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the
transport of class II-Ii chain complexes to lysosomes, while in mature DCs,
elevated cathepsin S activity results in efficient delivery of class II alphabeta
dimers to the plasma membrane. Cathepsin S is not controlled transcriptionally
but by a novel mechanism involving alterations in the expression and localization
of an endogenous cathepsin S inhibitor cystatin C. Thus, the ratio of cystatin C
to cathepsin S in developing DCs helps to determine the fate of newly synthesized
MHC class II molecules.
PMID- 9657148
TI - Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in
abnormal perinuclear clustering of mitochondria.
AB - Mouse kif5B gene was disrupted by homologous recombination. kif5B-/- mice were
embryonic lethal with a severe growth retardation at 9.5-11.5 days postcoitum. To
analyze the significance of this conventional kinesin heavy chain in organelle
transport, we studied the distribution of major organelles in the extraembryonic
cells. The null mutant cells impaired lysosomal dispersion, while brefeldin A
could normally induce the breakdown of their Golgi apparatus. More prominently,
their mitochondria abnormally clustered in the perinuclear region. This
mitochondrial phenotype was reversed by an exogenous expression of KIF5B, and a
subcellular fractionation revealed that KIF5B is associated with mitochondria.
These data collectively indicate that kinesin is essential for mitochondrial and
lysosomal dispersion rather than for the Golgi-to-ER traffic in these cells.
PMID- 9657149
TI - Thrombospondin-1 is a major activator of TGF-beta1 in vivo.
AB - The activity of TGF-beta1 is regulated primarily extracellularly where the
secreted latent form must be modified to expose the active molecule. Here we show
that thrombospondin-1 is responsible for a significant proportion of the
activation of TGF-beta1 in vivo. Histological abnormalities in young TGF-beta1
null and thrombospondin-1 null mice were strikingly similar in nine organ
systems. Lung and pancreas pathologies similar to those observed in TGF-beta1
null animals could be induced in wild-type pups by systemic treatment with a
peptide that blocked the activation of TGF-beta1 by thrombospondin-1. Although
these organs produced little active TGF-beta1 in thrombospondin null mice, when
pups were treated with a peptide derived from thrombospondin-1 that could
activate TGF-beta1, active cytokine was detected in situ, and the lung and
pancreatic abnormalities reverted toward wild type.
PMID- 9657150
TI - Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during
retinal development.
AB - We find that inactivation of a Drosophila homolog of the tumor suppressor APC (D
APC) causes retinal neuronal degeneration and pigment cell hypertrophy, a
phenotype remarkably similar to that found in humans with germline APC mutations.
Retinal degeneration in the D-APC mutant results from apoptotic cell death, which
accompanies a defect in neuronal differentiation. Reduction in the Drosophila
beta-catenin, Armadillo (Arm), rescues the differentiation defect and prevents
apoptosis in the D-APC mutant, while Arm overexpression mimics D-APC
inactivation. A mutation in dTCF, the DNA-binding protein required in Arm
mediated signal transduction, can eliminate the cell death without rescuing the
differentiation defect in D-APC mutants. Uncoupling of these two Arm-induced
processes suggests a novel role for the Arm/dTCF complex in the activation of
apoptosis.
PMID- 9657151
TI - Coordination of growth and cell division in the Drosophila wing.
AB - In most tissues, cell division is coordinated with increases in mass (i.e.,
growth). To understand this coordination, we altered rates of division in cell
clones or compartments of the Drosophila wing and measured the effects on growth.
Constitutive overproduction of the transcriptional regulator dE2F increased
expression of the S- and M-phase initiators Cyclin E and String (Cdc25), thereby
accelerating cell proliferation. Loss of dE2F or overproduction of its
corepressor, RBF, retarded cell proliferation. These manipulations altered cell
numbers over a 4- to 5-fold range but had little effect on clone or compartment
sizes. Instead, changes in cell division rates were offset by changes in cell
size. We infer that dE2F and RBF function specifically in cell cycle control, and
that cell cycle acceleration is insufficient to stimulate growth. Variations in
dE2F activity could be used to coordinate cell division with growth.
PMID- 9657152
TI - Arabidopsis LEAFY COTYLEDON1 is sufficient to induce embryo development in
vegetative cells.
AB - The Arabidopsis LEAFY COTYLEDON1 (LEC1) gene is required for the specification of
cotyledon identity and the completion of embryo maturation. We isolated the LEC1
gene and showed that it functions at an early developmental stage to maintain
embryonic cell fate. The LEC1 gene encodes a transcription factor homolog, the
CCAAT box-binding factor HAP3 subunit. LEC1 RNA accumulates only during seed
development in embryo cell types and in endosperm tissue. Ectopic postembryonic
expression of the LEC1 gene in vegetative cells induces the expression of embryo
specific genes and initiates formation of embryo-like structures. Our results
suggest that LEC1 is an important regulator of embryo development that activates
the transcription of genes required for both embryo morphogenesis and cellular
differentiation.
PMID- 9657153
TI - Constitutive expression of the CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene disrupts
circadian rhythms and suppresses its own expression.
AB - The CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene encodes a MYB-related transcription
factor involved in the phytochrome induction of a light-harvesting chlorophyll
a/b-protein (Lhcb) gene. Expression of the CCA1 gene is transiently induced by
phytochrome and oscillates with a circadian rhythm. Constitutive expression of
CCA1 protein in transgenic plants abolished the circadian rhythm of several genes
with dramatically different phases. These plants also had longer hypocotyls and
delayed flowering, developmental processes regulated by light and the circadian
clock. Furthermore, the expression of both endogenous CCA1 and the related LHY
gene was suppressed. Our results suggest that CCA1 is a part of a feedback loop
that is closely associated with the circadian clock in Arabidopsis.
PMID- 9657154
TI - The late elongated hypocotyl mutation of Arabidopsis disrupts circadian rhythms
and the photoperiodic control of flowering.
AB - The dominant late elongated hypocotyl (lhy) mutation of Arabidopsis disrupted
circadian clock regulation of gene expression and leaf movements and caused
flowering to occur independently of photoperiod. LHY was shown to encode a MYB
DNA-binding protein. In wild-type plants, the LHY mRNA showed a circadian pattern
of expression with a peak around dawn but in the mutant was expressed constantly
at high levels. Increased LHY expression from a transgene caused the endogenous
gene to be expressed at a constant level, suggesting that LHY was part of a
feedback circuit that regulated its own expression. Thus, constant expression of
LHY disrupts several distinct circadian rhythms in Arabidopsis, and LHY may be
closely associated with the central oscillator of the circadian clock.
PMID- 9657155
TI - Complementation cloning of NEMO, a component of the IkappaB kinase complex
essential for NF-kappaB activation.
AB - We have characterized a flat cellular variant of HTLV-1 Tax-transformed rat
fibroblasts, 5R, which is unresponsive to all tested NF-kappaB activating
stimuli, and we report here its genetic complementation. The recovered full
length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which
contains a putative leucine zipper motif. This protein is absent from 5R cells,
is part of the high molecular weight IkappaB kinase complex, and is required for
its formation. In vitro, NEMO can homodimerize and directly interacts with IKK-2.
The NEMO cDNA was also able to complement another NF-kappaB-unresponsive cell
line, 1.3E2, in which the protein is also absent, allowing us to demonstrate that
this factor is required not only for Tax but also for LPS, PMA, and IL-1
stimulation of NF-kappaB activity.
PMID- 9657156
TI - A critical role for amino-terminal glutamine/asparagine repeats in the formation
and propagation of a yeast prion.
AB - The yeast [PSI+] factor propagates by a prion-like mechanism involving self
replicating Sup35p amyloids. We identified multiple Sup35p mutants that either
are poorly recruited into, or cause curing of, wildtype amyloids in vivo. In
vitro, these mutants showed markedly decreased rates of amyloid formation,
strongly supporting the protein-only prion hypothesis. Kinetic analysis suggests
that the prion state replicates by accelerating slow conformational changes
rather than by providing stable nuclei. Strikingly, our mutations map exclusively
within a short glutamine/asparagine-rich region of Sup35p, and all but one occur
at polar residues. Even after replacement of this region with polyglutamine,
Sup35p retains its ability to form amyloids. These and other considerations
suggest similarities between the prion-like propagation of [PSI+] and
polyglutamine-mediated pathogenesis of several neurodegenerative diseases.
PMID- 9657157
TI - Ceruminolytic agents.
PMID- 9657158
TI - Endogenous lipid (cholesterol) pneumonia associated with bronchogenic carcinoma
in a cat.
AB - An 11-year-old, female domestic longhair was presented for dyspnea, vomiting, and
left forelimb lameness. A mass in the left caudal lung lobe was seen on thoracic
radiographs. The mass was resected during thoracotomy, and histopathology
confirmed a diagnosis of endogenous lipid pneumonia. The cat recovered slowly
from surgery and was euthanized 11 days following discharge because of persistent
respiratory difficulties. Necropsy findings included lipid pneumonia and
bronchogenic carcinoma, with probable tumor metastasis to the small intestine,
spleen, kidney, and left triceps muscle.
PMID- 9657159
TI - Cutaneous mast cell tumors in cats: 32 cases (1991-1994).
AB - Case records of 32 cats with cutaneous mast cell tumors (CMCTs) were reviewed.
Using the Patnaik system for grading canine mast cell tumors, the relationships
between histopathological grade and patient survival time and tumor recurrence
were examined. Tumor histopathological grade had no prognostic significance. One
, two-, and three-year tumor recurrence rates following surgical excision were
16%, 19%, and 13%, respectively. Incomplete excision was not associated with a
higher rate of tumor recurrence.
PMID- 9657160
TI - Gastrointestinal adenocarcinomas metastatic to the testes and associated
structures in three dogs.
AB - Primary testicular neoplasms are common in dogs, but metastases to the testes are
rare. Three dogs had enlargement of the testes and associated structures. Upon
histological examination, the enlargements were due to metastatic
adenocarcinomas. Further examination identified the gastrointestinal tract as the
primary site of the metastatic neoplasms in all three cases. The testicular
metastases reflected widespread metastatic disease. When metastatic
adenocarcinoma is found in the testes and associated structures in dogs, the
gastrointestinal tract should be examined closely for a primary tumor site.
PMID- 9657161
TI - Infantile desmoid-type fibromatosis in an Akita puppy.
AB - A 10-week-old Akita puppy was evaluated for a reported umbilical hernia. Repair
of the hernia had been attempted three times prior to referral. A defect in the
ventral abdominal wall with an associated soft-tissue mass was identified on
abdominal radiographs. Exploratory surgery was performed; the mass was resected
and the abdominal wall defect was repaired. Histopathological evaluation of the
mass was consistent with infantile desmoid-type fibromatosis.
PMID- 9657162
TI - Malignant mesenchymoma associated with an unusual vasoinvasive metastasis in a
dog.
AB - A case of a malignant mesenchymoma with an unusual, vasoinvasive, metastatic
behavior in a three-year-old, intact female basset hound is presented. Malignant
mesenchymomas are rare neoplasms in humans and in dogs. No previous reports of a
malignant mesenchymoma with vasoinvasive metastasis in the dog were found in the
literature. The constituent neoplasms are discussed in relation to reports in the
human and veterinary literature, and a potential etiology for this unique
presentation is hypothesized.
PMID- 9657163
TI - Lymphangiosarcoma in a dog presenting with massive head and neck swelling.
AB - A three-year-old, neutered male Chesapeake Bay retriever was presented for acute
onset of severe, progressive swelling of the head, neck, and cranial trunk.
Diffuse lymphangiosarcoma involving the superficial and deep dermis and
subcutaneous tissue was observed on skin biopsies. Lymphangiosarcoma is a rarely
reported tumor of the lymphatic system in dogs and cats. The importance of
obtaining skin biopsies in animals with acute edema of unknown etiology is
emphasized. Additionally, neoplasia should be considered as a potential diagnosis
in a dog with an acute onset of edema.
PMID- 9657164
TI - Spinal epidural empyema in two dogs.
AB - Extensive, diffuse, epidural spinal cord compression was visualized
myelographically in two dogs presented for rapid development of nonambulatory
tetraparesis and paraplegia, respectively. Purulent fluid containing bacterial
organisms was aspirated percutaneously under fluoroscopic guidance from the
epidural space of each dog. One dog responded poorly to aggressive medical
therapy, which included installation of an epidural lavage and drainage system.
Both dogs were euthanized due to the severe nature of their disorder and the poor
prognosis. Spinal epidural empyema (i.e., abscess) is a rare condition in humans
and has not been reported previously in the veterinary literature. Spinal
epidural empyema should be considered as a differential diagnosis in dogs
presenting with painful myelopathies, especially when accompanied by fever.
PMID- 9657166
TI - Uroperitoneum in cats: 26 cases (1986-1995).
AB - Uroperitoneum (UP) was diagnosed in 26 cats. Trauma was the most common cause
(84.6%), including blunt abdominal trauma (59.1%), urethral catheterization
(31.8%), and bladder expression (9.1%). The bladder was the most frequent site of
urine leakage following blunt abdominal trauma (84.6%), while the urethra was the
most common site following catheterization (71.4%). Common historical complaints
were anuria (53.8%) and vomiting (50%). On physical examination, the bladders
were palpable in nine (69%) of 13 cases; four of the nine had ruptured bladders.
The ability to urinate did not exclude a diagnosis of UP since four
noncatheterized cases reportedly urinated. Twenty-five cases were azotemic on
presentation. The creatinine or potassium (K+) concentration in the serum
compared to that in the peritoneal effusion (mean ratio, 1:2 and 1:1.9,
respectively) was a useful indicator for UP. When performed, positive contrast
radiography was diagnostic. Drainage of urine from the peritoneal cavity appeared
to improve patient stabilization. Morbidity and mortality depended largely on the
severity of associated injuries.
PMID- 9657165
TI - Surgical and chemotherapeutic treatment of alveolar echinococcosis in a dog.
AB - Surgical removal of macroscopically detectable metacestode tissue followed by
postoperative chemotherapy according to established human protocols resulted in
complete clinical remission and immediate normalization of hyperglobulinemia in a
dog with alveolar echinococcosis (AE). The disease is caused by the metacestode
stage of the cestode, Echinococcus multilocularis. In endemic areas, AE should be
included in the differential diagnosis of polycystic liver masses, especially if
concomitant hyperglobulinemia is present. However, the importance of AE is not
only the disease of the single dog itself but also the potential risk of
infection for humans in an endemic area.
PMID- 9657167
TI - Morbidity and mortality associated with anesthetic management in small animal
veterinary practice in Ontario.
AB - During 1993, 66 small animal practices participated in a prospective study to
evaluate the incidence and details of anesthetic-related morbidity and mortality.
Considering a total of 8,087 dogs and 8,702 cats undergoing anesthesia, the
incidences of complications were 2.1% and 1.3%, respectively. Death occurred in
0.11% and 0.1% of cases, respectively. Logistic regression models were developed
and showed that a significant odds ratio (OR) of complications in dogs was
associated with xylazine (OR, 91.5); heart rate monitoring (OR, 3.2); American
Society of Anesthesiologists (ASA) 3, 4, or 5 classification (OR, 2.5);
isoflurane (OR, 2.4); butorphanol (OR, 0.35); technician presence (OR, 0.26);
acepromazine (OR, 0.24); ketamine (OR, 0.21); and mask induction (OR, 0.2).
Complications in cats were associated with ASA 3, 4, or 5 classification (OR,
5.3); diazepam (OR, 4.1); intubation (OR, 1.7); butorphanol (OR, 0.45); and
ketamine (OR, 0.17). Cardiac arrest in dogs was associated with xylazine (OR,
43.6) and ASA 3, 4, or 5 classification (OR, 7.1). Cardiac arrest in cats was
associated with ASA 3, 4, or 5 classification (OR, 21.6) and technician presence
(OR, 0.19). This paper reports the incidences of complications and cardiac arrest
in small animal practice and identifies common complications and factors that may
influence anesthetic morbidity and mortality. This information may be useful in
comparing anesthetic management practices.
PMID- 9657168
TI - Early detection of canine hip dysplasia: comparison of two palpation and five
radiographic methods.
AB - Hip joint laxity was evaluated in four breeds (i.e., greyhound, Labrador
retriever, Irish setter, hound mixed-breed) of puppies (n=32) by Ortolani's and
Bardens' maneuvers, by subjective assessment of radiographs (Orthopedic
Foundation for Animals [OFA] method), and by four radiographic measurement
indices. Puppies were studied at four, six-to-10, 16-to-18, and 52 weeks of age.
The purpose of this study was to compare palpation and radiographic methods of
hip laxity detection in puppies for predicting the development of degenerative
joint disease (DJD) by one year of age. Twenty-seven (42%) hips developed DJD.
Ortolani's method was not a reliable predictor of hip dysplasia at six-to-10
weeks; it was significantly predictive at 16-to-18 weeks but had a high incidence
of false negatives. Bardens' and subjective (OFA) assessment methods were not
reliable at six-to-10 or 16-to-18 weeks. Radiographic measurements taken with
femurs in a neutral position and hips distracted (distraction index [DI] and
Norberg angle) and measurements taken with femurs extended in OFA position
(Norberg angle) of six- to 10-week-old puppies accurately predicted DJD
occurrence by one year of age (p less than 0.01). Distraction index measurement
(PennHIP method) was the most accurate in predicting the development of DJD (p
less than 0.001). Distraction index radiography in puppies six-to-10 and 16-to-18
weeks of age was the most reliable predictor of hip dysplasia. Norberg angle
measurement was more reliable during hip distraction than when hips were measured
in the OFA position in 16- to 18-week-old puppies, but had similar reliability in
six- to 10-week-old puppies.
PMID- 9657169
TI - The effects of stains and investigators on assessment of morphology of canine
spermatozoa.
AB - Percentage and types of morphological abnormalities found in canine spermatozoa
were evaluated by three investigators using three stains (Giemsa-Wright stain
[Diff-Quik], eosin Y/nigrosin [Hancock], and eosin B/nigrosin [Society for
Theriogenology morphology stain] with conventional light microscopy, compared to
phase contrast microscopy on unstained samples. The percentage of spermatozoa
with abnormal heads, midpieces, and tails varied by technique and by
investigator. Average percentages of morphologically normal spermatozoa were
significantly higher in samples stained with Diff-Quik and samples examined by
phase contrast microscopy than in samples stained with Hancock or Society for
Theriogenology morphology stains. No effect of investigator on the percentage of
morphologically normal spermatozoa was assessed. Results suggest that staining or
preparation technique may alter the morphology of canine spermatozoa
artifactually.
PMID- 9657170
TI - Urinary stress incontinence: surgical treatment.
PMID- 9657171
TI - A possible link between stress urinary incontinence and detrusor instability in
the female--urodynamic (pressure/flow) data and speculative considerations.
AB - The aim of the present investigation was to check voiding mechanics in women with
stress urinary incontinence (SUI) for differences between patients with stable
bladders and those with detrusor instability (DI). There were 70 females, 35 with
stable and 35 with unstable bladders, who had urodynamically proven SUI. All
underwent medium-fill water cystometry and pressure/flow studies. A relatively
enhanced detrusor contractility, mirrored by higher values of maximum external
voiding power and shortening velocity, could be found in the unstable patients.
Of these, 27 were reassessed urodynamically following surgical cure of the SUI.
After the operative treatment 17 of the 27 showed stable bladders and a reduced
detrusor contractility, but no reduced contractility was found in the other 10,
whose bladders remained unstable. The data reported may suggest that the factor
responsible for 'idiopathic' DI in SUI patients would also be able to yield
enhanced bladder mechanical capability. It was tentatively assumed that this
factor involves an increased urethral sensitivity, possibly secondary to
incompetence of the urethral closure mechanism, and persisting at times even
should SUI be surgically relieved.
PMID- 9657172
TI - Ultrasonographic estimation of postpartum postvoid residual bladder volume: a
comparison between transabdominal and transvaginal ultrasonography.
AB - Postvoid residual bladder volume (PVRBV) was estimated in 89 patients with
postpartum urinary retention using two ultrasonographic volume estimation
methods. The PVRBV estimated by transabdominal and transvaginal ultrasonography
are compared using the plot of difference against mean and the paired t-test.
Neither showed any significant difference between the two methods (paired sample
t-test, P > 0.05). The two methods have high correlation coefficient of 0.903
(Spearman's correlation, P < 0.0001). Either ultrasonographic volume estimation
method gives reasonable bladder volume assessment in postpartum patients and
could be used interchangeably as the clinical situation requires.
PMID- 9657173
TI - Transurethral collagen injection for female stress incontinence.
AB - Periurethral collagen injections have been used to treat female urinary
incontinence secondary to intrinsic sphincteric deficiency (ISD). As an
alternative, a transurethral submucosal collagen injection was used in 33
consecutive women suffering from stress incontinence secondary to ISD at Tulane
University Medical Center. Prior to the procedure, careful clinical examination
with a videofluorourodynamic study was performed for each case. The procedure was
carried out under local anesthesia assisted with monitored anesthesia care (MAC).
The collagen was injected transurethrally by the long collagen needle (C. R.
Bard). In the first 11 cases the average cumulative collagen injected per patient
was 6.1 ml, whereas in the last 22 cases the average was 3.5 ml. As a result of
the injection 16 patients were dry (48.5%) and 11 were improved (33.3%), with an
overall success rate of 81.8%. The injection failed in 6 patients (18.1%). The
mean follow-up was 18.8 months, with a range of 2-33 months. In the successful
group there was a significant decrease in pretreatment frequency, from an average
of 8 to 4.9 (P = 0.005) and in nocturia from an average of 2.14 to 0.76 (P =
0.001). Also, there was a significant decrease in the number of pads, from an
average of 3.7 to 1.1 (P = 0.001). The stress leak-point pressure showed a
significant increase, from an average of 68.1 to 93.5 cm H2O (P = 0.03). There
was no relation between grade of incontinence and the success of the injection.
Two cases suffered from temporary urinary retention. This study revealed that the
transurethral submucosal collagen injection is an effective method for treating
cases of intrinsic sphincteric deficiency. The volume of collagen required to
produce the seal effect is small and it may decrease the reinjection rate. As
experience is gained, the procedure time is typically 15 minutes. This makes it a
reliable, cost-effective and well-controlled method. However, it has a learning
curve and the cystoscope instruments require minor adaptation for its use.
PMID- 9657174
TI - Development of generic models for ambulatory vaginal surgery--a preliminary
report.
AB - Generic guidelines are applied to reconstructive vaginal operations, so as to
convert them to ambulatory procedures. Prototype operations are described and
analyzed. These included conceptualizing vaginal prolapse as a type of
intussusception caused by vaginal and ligamentous laxity in the middle or
posterior parts of the vagina; the avoidance of vaginal excision, excessive
tension, and refashioning excess vaginal tissue from width to length or into a
partial double-layered repair; the creation of artificial neoligaments; the
prevention of urinary retention by avoiding tightness in the bladder neck area;
local anesthetic infiltration; and buttressing vaginal tissue during wound
healing. A total of 108 patients underwent vaginal surgery on an ambulatory or
overnight stay basis, 72 under local anesthesia/midazolam. Minimal postoperative
pain and the absence of catheterization reduced hospital stay from a statewide
mean of 8 days to 1 day, and return to normal activities from 6 weeks to 7-10
days. Cure rates (18 months) were: uterovaginal prolapse 22/22, infracoccygeal
sacropexy 21/23, rectocele 36/38, cystocele/anterior vaginal wall prolapse 21/25.
Applied as prototypes to reconstructive vaginal surgery, the operations appear to
be as effective as traditional techniques but far less invasive. They have the
potential to assist working mothers, the old and infirm, and save the community
up to $5,500 per patient. It is hoped that the generic models presented may act
as a basis for the future development of ambulatory vaginal surgical techniques.
PMID- 9657175
TI - A new concept of the anatomy of the anal sphincter mechanism and the physiology
of defecation: mass contraction of the pelvic floor muscles.
AB - We have previously demonstrated both anatomically and physiologically that the
external anal (EAS) and urethral (EUS) sphincters and the bulbocavernosus muscle
(BC) originate from the puborectalis muscle (PR). It is hypothesized that
stimulation of any of these muscles would lead to contraction of all the others.
Because the levator ani (pubococcygeus) muscle (LA) also has the same innervation
as the above-mentioned muscles, it is further suggested that it, too, contracts
reflexly upon stimulation of any of those muscles. The purpose of this study was
to test this hypothesis. The study comprised 18 healthy volunteers (mean age 36.6
+/- 8.4 years; 10 men, 8 women). The EAS was stimulated and the response of the
EUS, PR, LA and BC was determined. Each muscle was thereafter stimulated
separately and the response of the other pelvic floor muscles registered.
Stimulation of any of the pelvic floor muscles effected an increased EMG activity
of the rest of the muscles. The muscle contraction was instantaneous with no
latency in all the muscles except the LA EMG activity, which showed a mean
latency of 21.3 +/- 6.6 ms. The pelvic floor muscles' response seems to be
attributable to muscle stimulation both directly and indirectly through
activation of pudendal nerve fibers in the muscles. The study demonstrated that
the pelvic floor muscles behave as one muscle: they contract or relax en masse.
This 'mass contraction' might explain some of the physiologic phenomena that
occur during pelvic organ evacuation. However, besides this mass contraction, a
voluntary 'selective' individual muscle activity exists by which each individual
muscle acts independently of the others.
PMID- 9657176
TI - Uroflow in women: an overview and suggestions for the future.
AB - The literature on uroflowmetry in women is presented and evaluated. Uroflowmeters
are described and found generally sufficiently accurate, although the errors
arising from electronic evaluation may invalidate the test. Six flow curve
patterns are proposed in accordance with described pathological conditions. From
the literature it is summarized that the normal Qmax is 20-36 ml/s. Qmax is
linearly correlated to the voided volume, increasing by 5.6 ml/s/100 ml.
Pregnancy, age and menstrual cycle do not influence Qmax. Several pathological
conditions have been associated with specific flow curve patterns. These
conditions are described and associations with the proposed flow definitions
made.
PMID- 9657177
TI - Techniques of rectocele repair and their effects on bowel function.
AB - Gynecologists have traditionally evaluated rectocele repair by its effect on
vaginal function; coloproctologists have traditionally evaluated its effect on
bowel function. Hence different operative criteria and surgical techniques have
arisen, but with very little prospective, objective evaluation. The purpose of
this review is to describe the surgical techniques used to repair the rectocele
and the most common investigations used during its evaluation. Anorectal
investigations identify concomitant pathology, may explain pathophysiology,
provide objective outcome criteria and attempt to predict the patients that will
most benefit from surgery. However, because of the complex neuromuscular,
physiological and mechanical interactions that contribute to impaired rectal
emptying, their usefulness in improving functional outcome has been limited. Many
patients experience improvement, but still are left with some symptoms of
impaired defecation despite anatomic correction.
PMID- 9657178
TI - The defunctionalized bladder.
AB - Supravesical urinary diversion without cystectomy is a common procedure performed
to manage a variety of lower urinary tract pathologies. The purpose of this
article is to review the complications associated with the bladder left in situ
and to relate this to the female patient. Complications related to the
defunctionalized bladder include pyocystis, hemorrhage, pain/spasm and neoplastic
transformation. The defunctionalized bladder also has implications for sexual
function, pregnancy and undiversion. The risk factors for complications are
chronic infection, inadequate drainage, interstitial cystitis and previous
irradiation. The incidence of neoplastic change in the defunctionalized bladder
is low, but long-term follow-up is advised, as carcinoma could develop many
decades after diversion. Sexual function following urinary diversion is better
preserved when the bladder is retained.
PMID- 9657179
TI - Preoperative contrast ultrasonographic diagnosis of patent urachal sinus.
AB - A patent urachal sinus, as well as other congenital urachal anomalies, may be at
risk of injury during laparoscopy. Leakage of fluid at the midline site of trocar
entry is the usual postoperative sign of injury to a patent urachal sinus. Pre
operative diagnosis of this anomaly can prevent injury during laparoscopy. We
describe a contrast ultrasound technique for diagnosis of patent urachal sinus.
PMID- 9657180
TI - Total genitourinary reconstruction in adult female epispadias: a report of 2
cases and literature review.
AB - Female incontinent episadias is a very rare congenital anomaly presenting in
childhood. We report 2 cases of adults presenting with this anomaly. These were
treated by total genitourinary reconstruction in a single stage using a combined
perineal abdominal approach, with satisfactory results. We recommend this
technique as the procedure of choice in adults presenting with this rare anomaly.
PMID- 9657181
TI - Recurrence of stress incontinence after vault suspension: can it be prevented?
AB - Management of vault prolapse in a patient who has previously undergone successful
colposuspension has not been considered in the literature. The two cases
presented highlight the risk of incontinence and illustrate measures that should
help to reduce it. The approach aims to reveal potential stress incontinence and
to prevent excessive stretching of the upper anterior vaginal wall during
surgical correction. Potential stress incontinence is revealed by a cough stress
test while reducing the prolapse without a speculum, a 'pessary test' for a few
days, and urodynamics both with and without a pessary. Patients with potential
incontinence undergo perineal ultrasound to assess bladder neck position. If
sacrospinous fixation is used, epidural anesthesia is recommended so as to allow
the patient to cough during the procedure to ensure accurate suture placement.
When sacrocolpopexy is done, preoperative assessment of the degree of 'safe
elevation' ensures accurate suture placement.
PMID- 9657182
TI - Microvascular decompression of the left lateral medulla oblongata for severe
refractory neurogenic hypertension.
AB - OBJECTIVE: To demonstrate that microvascular decompression of the left medulla
oblongata is a safe and effective modality for treating elevated blood pressure
in patients with severe medically refractory "essential" hypertension (HTN).
METHODS: Twelve patients with medically intractable HTN with or without autonomic
dysreflexia underwent microvascular decompression of the left rostral
ventrolateral medulla oblongata. Causes such as pheochromocytoma, carcinoid
syndrome, and renal disease were ruled out before surgery. Indications for
surgery included systolic blood pressures greater than 180 mm Hg refractory to
three or more medications, severe blood pressure lability, or medically resistant
HTN at systolic pressures greater than 160 mm Hg associated with autonomic
dysreflexia and/or magnetic resonance images demonstrating left medullary
compression. The median age and follow-up duration were 51 years and 4.1 years,
respectively. RESULTS: Ten of 12 patients experienced reductions in systolic
blood pressure greater than 20 mm Hg. Of these 10 patients, pressure reductions
were temporary (6 mo) in two. Seven of eight patients experienced improvement in
blood pressure lability and/or autonomic dysreflexia, with five patients showing
sustained improvements. CONCLUSION: Microvascular decompression of the left
rostral ventrolateral medulla oblongata may be an effective treatment modality
for patients suffering from severe HTN and/or autonomic dysreflexia refractory to
medical management.
PMID- 9657183
TI - Hypothermic circulatory arrest in neurovascular surgery: evolving indications and
predictors of patient outcome.
AB - OBJECTIVE: One of the largest contemporary neurosurgical experiences with
hypothermic circulatory arrest was analyzed for trends in patient selection and
clinical variables affecting outcome. METHODS: During a 12-year period, 60
patients underwent 62 circulatory arrest procedures: 54 had posterior circulation
aneurysms, 4 had anterior circulation aneurysms, and 2 had other lesions
(hemangioblastoma and vertebral artery atherosclerosis). RESULTS: The surgical
morbidity and mortality rates associated with hypothermic circulatory arrest were
13.3 and 8.3%, respectively. At late follow-up, 76% of the patients had good
outcomes (Glasgow Outcome Scale scores of 1 and 2), 5% had poor outcomes (Glasgow
Outcome Scale scores of 3 and 4), and 18% had died. After 1992, circulatory
arrest was limited to posterior circulation aneurysms and included increasing
numbers of basilar trunk aneurysms. Patient outcome correlated with preoperative
neurological condition (admission Glasgow Coma Scale score, P < 0.001; Hunt and
Hess grade, P = 0.037; and age, P = 0.007). Preservation of perforating arteries
was paramount to achieving a good outcome (P = 0.005); duration of circulatory
arrest was not. CONCLUSION: Current indications for hypothermic circulatory
arrest include only giant and complex posterior circulation aneurysms that cannot
be treated using conventional techniques or that recur after endovascular
coiling. Surgical morbidity and mortality rates reflect the increasing complexity
of the aneurysms treated but are still more favorable than the natural history of
these lesions. This experience demonstrates that management in specialized
neurovascular centers can minimize the morbidity associated with circulatory
arrest so that it remains a viable treatment option for complex posterior
circulation aneurysms.
PMID- 9657184
TI - Risk factors for multiple intracranial aneurysms.
AB - OBJECTIVE: Risk factors that predispose to the formation of multiple intracranial
aneurysms, which are present in up to 34% of patients with intracranial
aneurysms, are not well defined. In this study, we examined the association
between known risk factors for cerebrovascular disease and presence of multiple
intracranial aneurysms. METHODS: We reviewed the medical records and results of
conventional angiography in all patients with a diagnosis of intracranial
aneurysms admitted to the Johns Hopkins University hospital between January 1990
and June 1997. We determined the independent association between various
cerebrovascular risk factors and the presence of multiple aneurysms using
logistic regression analysis. RESULTS: Of 419 patients admitted with intracranial
aneurysms (298 ruptured and 121 unruptured), 127 (30%) had multiple intracranial
aneurysms. In univariate analysis, female gender (odds ratio [OR] = 1.9; 95%
confidence interval [CI], 1.1-3.3) and cigarette smoking at any time (OR = 1.8;
95% CI, 1.1-3.0) were significantly associated with presence of multiple
aneurysms. In the multivariate analysis, cigarette smoking at any time (OR = 1.7;
95% CI, 1.1-2.8) and female gender (OR = 2.1; 95% CI 1.2-3.5) remained
significantly associated with multiple aneurysms. Hypertension, diabetes
mellitus, and alcohol and illicit drug use were not significantly associated with
presence of multiple aneurysms. CONCLUSION: Cigarette smoking and female gender
seem to increase the risk for multiple aneurysms in patients predisposed to
intracranial aneurysm formation. Further studies are required to investigate the
mechanism underlying the association between cigarette smoking and intracranial
aneurysm formation.
PMID- 9657185
TI - Treatment of hemangioblastomas in von Hippel-Lindau disease with linear
accelerator-based radiosurgery.
AB - OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat
hemangioblastomas, particularly those that are in surgically inaccessible
locations or that are multiple, as is common in von Hippel-Lindau disease. The
purpose of this study was to retrospectively evaluate the effectiveness of
radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996,
29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated
with linear accelerator-based radiosurgery. The mean patient age was 40 years
(range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy
(range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3).
Tumor response was evaluated in serial, contrast-enhanced, computed tomographic
and magnetic resonance imaging scans. The mean follow-up period was 43 months
(range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas
progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%)
remained unchanged in size. Five of nine patients with symptoms referable to
treated hemangioblastomas experienced symptomatic improvement. During the follow
up period, one patient died as a result of progression of untreated
hemangioblastomas in the cervical spine. Three patients developed radiation
necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring
is limited, stereotactic radiosurgery provides a high likelihood of local control
of hemangioblastomas and is an attractive alternative to multiple surgical
procedures for patients with von Hippel-Lindau disease.
PMID- 9657186
TI - Somatosensory evoked potential monitoring during positioning of the patient for
posterior fossa surgery in the semisitting position.
AB - OBJECTIVE: Midcervical flexion myelopathy is a rare but well-known complication
of posterior fossa surgery. To reduce the risk, we routinely used somatosensory
evoked potential (SSEP) monitoring during positioning of the patient. METHODS:
Fifty-five consecutive patients were operated on for posterior fossa lesions in
the semisitting position via a median (5 patients) or a lateral (50 patients)
suboccipital approach. During positioning, monitoring of SSEPs by stimulation of
the tibial nerve (T-SSEP) as well as by stimulation of the median nerve (M-SSEP)
was established. In the case of pronounced SSEP changes, the head was
repositioned. Surgery was started after SSEP recordings were unchanged as
compared to the baseline investigation. RESULTS: Effective monitoring was
possible in all cases. Whereas M-SSEP recordings showed no changes while placing
patients in the sitting position, T-SSEP recordings were altered in 14 cases
(25%). In cases using the midline approach, SSEP changes were never so pronounced
to require repositioning of the head. Head flexion and rotation resulted in
significant changes of T-SSEP recordings in eight patients (14.5%), requiring
repositioning. In two cases, an amplitude loss was noted. In only two of these
eight patients were M-SSEP recordings markedly changed. SSEP recordings after
repositioning disclosed recovery of spinal cord function. In no patient were
clinical signs of myelopathy observed postoperatively. CONCLUSION: We observed a
high incidence of pronounced changes of T-SSEP recordings when the patient's head
was flexed and rotated for lateral suboccipital craniotomy in the semisitting
position. Despite the low specificity monitoring of T-SSEPs during positioning of
the patient for posterior fossa surgery, the semisitting position is strongly
recommended.
PMID- 9657187
TI - Cervical spondylotic myelopathy: surgical results and factors affecting
prognosis.
AB - OBJECTIVE: A variety of factors may affect surgical outcome in patients with
cervical spondylotic myelopathy. The aim of this study is to determine these
factors on the basis of preoperative radiological and clinical data. METHODS: To
assess the factors affecting postoperative outcome after surgery for cervical
spondylotic myelopathy, the clinical and radiological data of 27 patients with
cervical spondylotic myelopathy were reviewed. Functional and neurological
statuses were assessed using the Japanese Orthopaedic Association (JOA) scale
modified by Benzel. In all patients, the effect of age, symptom duration,
cervical curvature, presence or absence of preoperative high signal intensity
within the spinal cord as revealed by T2-weighted magnetic resonance imaging, and
diameters of the spinal canal and vertebral body on pre- and postoperative
neurological statuses were investigated. Plain radiographs were obtained for all
patients, magnetic resonance images for 21 patients (77.8%), computed tomographic
scans for 13 patients (48.1%), myelograms for 6 patients (22.2%), and computed
tomographic myelograms for 4 patients (14.8%). There were five patients with a
JOA score of 10, six patients with a JOA score of 11, six patients with a JOA
score of 12, four patients with a JOA score of 13, four patients with a JOA score
of 14, one patient with a JOA score of 15, and one patient with a JOA score of
16. All patients underwent cervical laminectomies. The mean follow-up period was
54.1 months. The final neurological examinations revealed improvement in the JOA
scores of 85.1 % of the patients. RESULTS: Statistical analysis of all patients
revealed mean JOA scores of 12.185 +/- 1.618 and 14.370 +/- 2.15 before surgery
and at final examination, respectively. The difference between the preoperative
JOA score and the final JOA score was determined to be statistically significant
(P < 0.0001). Statistical analyses also showed better neurological improvement in
patients younger than 60 years and in patients with normal preoperative cervical
lordosis. Although patients without preoperative high signal intensity of the
spinal cord showed a better improvement rate than did patients with preoperative
high signal intensity, the determined difference was statistically insignificant.
CONCLUSION: It can be concluded that age and abnormal cervical curvature predict
less postoperative neurological improvement. The presence of preoperative high
signal intensity within the spinal cord may also reflect less neurological
improvement.
PMID- 9657188
TI - A prospective randomized study of anterior single-level cervical disc operations
with long-term follow-up: surgical fusion is unnecessary.
AB - OBJECTIVE: After 40 years of experience with anterior cervical operations,
whether to fuse is still controversial. This study seeks to answer this question.
METHODS: In this prospective randomized study, we operated on 91 patients with
single-level cervical root compression using three different methods: 1)
discectomy without fusion, 2) fusion with autologous bone graft, and 3) fusion
with autologous bone graft plus plating. RESULTS: After 4 years of follow-up, the
radiological results indicated that complete bony union was achieved in almost
all cases. A slight kyphosis developed in 62.5% of the patients who had undergone
discectomy, 40% of the patients who had undergone fusion, and 44% of the patients
who had undergone fusion plus plating (not significant). The clinical outcomes
were good for 76% of the patients who had undergone discectomy, 82% who had
undergone fusion, and 73% who had undergone fusion plus plating. The outcomes
were poor in 0, 4, and 4%, respectively (not significant). CONCLUSION: According
to this study, satisfactory results can be achieved by performing simple
discectomy to treat single-level cervical root compressive disease.
PMID- 9657189
TI - Neurogenic sarcomas: experience at the University of Toronto.
AB - OBJECTIVE: Elucidation of the natural history and optimal management of
neurogenic sarcomas is not straightforward, because of diagnostic difficulties
and the low incidence of this disease. The majority of neurogenic sarcomas are
categorized and treated as soft tissue sarcomas, and only a few centers have
sufficient experience to add to our understanding of these malignant tumors. This
article proposes an algorithm for the management of these tumors. METHODS: A
cohort of 18 cases of neurogenic sarcoma (overall mean follow-up period after
oncological diagnosis, 33.7 mo), representing approximately 3% of all soft tissue
sarcomas treated at the University of Toronto Musculoskeletal Oncology Unit
(Toronto, Canada) between 1989 and 1995, were reviewed. The clinical and
pathological criteria used to establish the diagnosis of neurogenic sarcoma, the
presenting symptoms, the tumor size and grade, the ability to obtain tumor-free
margins during en bloc resection, the time to recurrence, and the overall
survival rates were noted. A centralized pathological review of the biopsy was
undertaken in all cases. RESULTS: A metastatic survey demonstrated localized
disease for 16 of the 18 patients. The overall management strategy for these 16
neurogenic sarcomas with localized disease was to obtain local control by en bloc
resection. Tumor size, tumor grade, and, most importantly, the ability to obtain
tumor-free margins were all relevant prognostic factors for survival. Tumor-free
surgical margins were obtained for 11 of 16 patients, with 9 of these 11 patients
remaining disease-free. In contrast, all patients for whom tumor-free margins
could not ultimately be achieved died as a result of their disease. CONCLUSION:
Based on our experience, we propose an algorithm for the management of these rare
tumors, for both optimal patient care and oncological research.
PMID- 9657190
TI - Postcontrast magnetic resonance imaging to predict progression of traumatic
epidural and subdural hematomas in the acute stage.
AB - OBJECTIVE: We investigated the possibility of predicting the progression of
traumatic epidural hematomas (EDHs) and subdural hematomas (SDHs), in the acute
stage, by using postcontrast magnetic resonance imaging (MRI) with gadolinium
diethylenetriaminepentaacetic acid. METHODS: From January 1990 through December
1996, 41 patients with 43 hematomas (21 EDHs and 22 SDHs) underwent postcontrast
MRI within 24 hours after injury. T1-weighted MRI was performed by using the spin
echo method, after the administration of 0.1 mmol/kg gadolinium
diethylenetriaminepentaacetic acid, immediately after computed tomographic
scanning. RESULTS: All of the enhanced hematomas were enlarged, whereas
nonenhanced hematomas, except for two SDHs with bleeding tendencies, remained
unchanged or decreased in volume. The prediction rates for enlargement with this
method were 100% (21 of 21) for EDHs and 91.0% (20 of 22) for SDHs. The
sensitivity of this test in predicting enlargement was 100% (15 of 15) for EDHs
and 81.8% (9 of 11) for SDHs. The specificity was 100% for both types of
hematomas. The enlargement rates for diffusely enhanced hematomas were
statistically greater than those for nonenhanced hematomas. All of the patients
with diffusely enhanced hematomas, which were found during surgery to exhibit
active bleeding points, experienced consciousness deterioration. CONCLUSION: We
conclude that diffuse enhancement indicates extravasation from broken vessels
that continue to bleed and that diffusely enhancing hematomas will be rapidly
enlarged. We think that postcontrast MRI can be very useful for predicting the
progression of acute EDHs and SDHs.
PMID- 9657191
TI - Untreated growing cranial fractures detected in late stage.
AB - OBJECTIVE: Because the great majority of published cases of treated growing
cranial fractures (GCFs) involved infants and children, the natural evolution of
untreated GCFs is not well known. The question of whether untreated GCFs may
cause progressive neurological deficits is controversial. METHODS: This
retrospective study is of GCFs treated between 1989 and 1997. Nine patients
(eight male patients and one female patient; median age, 20.5 yr) with GCFs who
underwent surgical intervention during the late stage are presented. The dural
and cranial defects were repaired, and additional decompressive surgical
procedures (cyst fenestration, n = 6; cyst excision, n = 1; cyst excision with
cystoperitoneal shunting, n = 2) were performed for all patients. This is the
largest of the published series. RESULTS: All of the patients had histories of
severe head trauma that occurred during childhood. The average age at the time of
the onset of symptoms was approximately 13.1 years, and the interval between head
injury and first symptom ranged from 8 to 13 years. All of the patients had lytic
lesions in the cranium. Headache was the most common symptom, and of eight
patients, seven improved completely and one improved partially. One of four
epileptic patients was seizure-free postoperatively. None of the paresis
improved, except in one patient. CONCLUSION: We conclude that untreated GCFs may
cause delayed onset neurological manifestations in addition to cranial growth
asymmetry. GCFs, discovered incidentally in adolescence or adulthood without any
neurological deficits, should be operated on as soon as feasible to prevent
further brain destruction. Cranioplasty with dural repair, in addition to cyst
fenestration, should be considered as the essential procedure for the treatment
of these lesions.
PMID- 9657192
TI - Resection and graft repair for localized hypertrophic neuropathy.
AB - OBJECTIVES: Formulation of surgical management recommendations for localized
hypertrophic mononeuropathy has been difficult because of the infrequency of the
lesion, lack of precise pathological diagnosis, and uncertainties regarding its
cause. The purpose of this retrospective review of the Louisiana State University
(LSU) experience with this unusual neuropathy was to evaluate the efficacy of
lesion resection and interposition grafting in its management. METHODS: The
charts of 15 patients operated on at LSU during a 15-year period with a
pathological diagnosis of localized hypertrophic neuropathy were reviewed.
RESULTS: Hypertrophic lesions were located on major named peripheral nerves of
the extremities, distributed equally to the upper and lower extremities. Family
history was negative for all patients, and entrapment or trauma, other than
previous surgery, were unlikely by symptom location or history. Weakness was the
most common presentation. The mean length of symptoms was 76 months. Atrophy,
sensory loss, Tinel's sign, focal tenderness, and a mass were found in the
majority of patients. Preoperative electrophysiological studies showed chronic
denervational changes in all patients. At surgery, if no action potential or one
of low amplitude was recorded across the lesion, the lesion was resected and an
autologous nerve graft measuring from 3.5 to 8.5 cm in length was interposed.
During follow-up periods of 1 or more years, seven of nine patients with
localized hypertrophic mononeuropathy treated with graft repairs were either
unchanged or improved. CONCLUSION: Localized hypertrophic mononeuropathy is a
progressive process associated with pathological nerve changes that correlate
with eventual severe functional loss. If intraoperative histological examination
shows onion bulb neuropathy and intraoperative nerve action potentials confirm a
nonfunctioning or poorly functioning segment, lesion resection with interposition
graft repair provides the possibility of some degree of recovery.
PMID- 9657193
TI - The anterior subtemporal, medial transpetrosal approach to the upper basilar
artery and ponto-mesencephalic junction.
AB - OBJECTIVE: To describe and anatomically analyze the amount of exposure provided
by an anterior subtemporal, medial transpetrosal approach to access the upper
third of the basilar artery, ventral mesencephalon, pons, and posterior cavernous
sinus. PATIENTS AND METHODS: The outcomes of six patients who underwent surgical
treatment via the anterior subtemporal, medial transpetrosal approach at our
institution during the past 2 years were reviewed. The series included three
patients with subarachnoid hemorrhage from low-lying basilar apex aneurysms, one
patient with intraparenchymal hemorrhage from a pontine cavernous malformation,
and two patients with slowly progressive cranial neuropathies secondary to
petroclival tumors. Thirty dry temporal bone specimens were also measured to
quantify the height of petrous bone resection and added proximal basilar artery
exposure. RESULTS: The surgical exposure was greatly enhanced in each instance,
allowing each lesion to be treated in a straightforward manner with minimal added
morbidity (one trochlear nerve palsy, one worsening of a preexistent oculomotor
nerve palsy). Our subsequent morphometric analysis indicates that an additional 1
to 1.5 cm of basilar artery, clivus, and pons exposure over that of a standard
anterior subtemporal approach is provided by this technique. CONCLUSION: This
approach combines the wide view of the subtemporal approach with the more
proximal exposure afforded by a medial petrosectomy. The widened visualization of
the ventral pons and mesencephalon minimizes cranial nerve morbidity, greatly
facilitates dissection of low-lying aneurysms, and provides proximal basilar
artery control that would otherwise be obscured by the petrous ridge.
PMID- 9657194
TI - Influence of isoflurane on myogenic motor evoked potentials to single and
multiple transcranial stimuli during nitrous oxide/opioid anesthesia.
AB - OBJECTIVE: Transcranial motor evoked potentials (tc-MEPs) are used to monitor the
spinal cord intraoperatively. Volatile anesthetics considerably depress
amplitudes of tc-MEPs. This study was undertaken to determine whether multipulse
stimulation might overcome this depressant effect. METHODS: In 10 patients
undergoing spinal surgery, incremental doses of isoflurane were added to a
nitrous oxide/opioid anesthetic regimen and maintained constant at 0.2, 0.4, and
0.6% end tidal for at least 15 minutes. tc-MEP responses to single-pulse and
trains of three and five (interstimulus interval, 2 ms) transcranial electrical
stimuli were recorded from the tibialis anterior muscles. RESULTS: Before the
addition of isoflurane, tc-MEPs were recordable in all patients, even with single
pulse stimuli (median amplitude, 428 microV). With 0.2% end-tidal isoflurane, tc
MEPs were recordable in eight patients with single-pulse stimulation and in all
patients with three and five successive stimuli. At 0.4% isoflurane, responses
were recordable in only one patient using single-pulse stimuli and in all
patients using three and five stimuli. With 0.6% isoflurane, tc-MEPs to trains of
three and five stimuli were recordable in all patients except one. The amplitude
of the responses obtained with 0.2, 0.4, and 0.6% end-tidal isoflurane was
significantly smaller than that of control responses (P < 0.05). CONCLUSION:
These data suggest that despite the powerful depressant effects of isoflurane on
myogenic motor responses, tc-MEP monitoring during isoflurane anesthesia may be
feasible, provided that multipulse stimulation paradigms are used and the
concentration of isoflurane does not exceed 1 minimal anesthetic concentration
unit.
PMID- 9657195
TI - Hemodynamic changes in arterial feeders and draining veins during embolotherapy
of arteriovenous malformations: an experimental study in a swine model.
AB - OBJECTIVE: Transcatheter assessment of changes in draining vein (DV) flow
velocity has been proposed recently as a potentially useful procedure for
hemodynamic monitoring of the progression of embolotherapy in cerebral
arteriovenous malformations (AVMs). We compared and contrasted changes in
hemodynamic parameters of arterial feeders (AFs) and DVs during experimental AVM
embolotherapy. METHODS: Carotid-jugular fistula-type AVM models were surgically
created in eight swine. Pre- and postembolization transcatheter mean AF and DV
pressures, DV-time average spectral peak velocity, and AF and DV pulsatility
indices were assessed. An expression, the peak systolic velocity minus end
diastolic velocity (Vs - Ved), was also used in evaluating the transvenous
Doppler spectra. Pre- and postembolization hemodynamic parameters were compared
statistically. RESULTS: Pre-embolization DV flow was pulsatile (Vs - Ved, 12 +/-
4.8 cm/s), with a mean DV velocity of 39.3 +/- 11.4 cm per second.
Postembolization, this changed to a less/nonpulsatile pattern (Vs - Ved, 5.4 +/-
2.7 cm/s; P = 0.0035) with a lower mean DV-average spectral peak velocity of 7.0
+/- 3.1 cm per second (P = 0.0001). The mean DV pressure was also reduced from
52.0 +/- 8.2 to 45.5 +/- 8.7 mm Hg (P = 0.0023). The mean AF pressure increased
from a mean of 79.5 +/- 15.5 to 96.8 +/- 16.2 mm Hg (P = 0.0004). The DV
pulsatility index values also increased from a mean of 0.3 +/- 0.2 to 1.1 +/- 0.5
(P = 0.0003). Periembolization objective hemodynamic changes were detected in the
DVs earlier than were the visually subjective angiographic changes observed
within the nidus. CONCLUSION: This preliminary study indicates that transvenous
assessment of average spectral peak velocity and wave pattern (Vs - Ved) may be
useful in the hemodynamic evaluation of AVM shunting. The convergence of these
two parameters to a range less than 10 cm per second after nidus embolization may
afford a theoretical advantage over AF pressure measurements when used for
objective and quantitative monitoring of endovascular embolotherapy.
PMID- 9657196
TI - Specific inhibition of apoptosis after cold-induced brain injury by moderate
postinjury hypothermia.
AB - OBJECTIVE: Apoptosis of neuronal cells plays a key role in many developmental and
pathological processes of the central nervous system. Deoxyribonucleic acid (DNA)
of cells undergoing apoptosis is cleaved by an endonuclease into oligonucleosoma
sized fragments. These fragments can be labeled using in situ terminal
deoxynucleotidyl transferase so that the apoptotic cells can be visualized by in
situ apoptotic staining. The model of cold-induced rat brain edema was used to
further examine this hypothesis. The protective effect of hypothermia was also
studied in this model of cold-induced brain injury. METHODS: Using a terminal
deoxynucleotidyl transferase-mediated deoxyuridine 5'-triphosphate-biotin nick
end labeling technique, the neuronal cells with DNA fragmentation in different
regions of the brains of rats subjected to cold-induced brain injury were
detected. The internucleosomal fragments of DNA in apoptotic cells were examined
using agarose gel electrophoresis. The animals were randomly divided into three
groups: 1) sham (n = 8); 2) cold-induced brain injury, killed at 12, 24, 48, 72,
and 168 hours after cold lesion (n = 10 for each time point); 3) hypothermia,
both mean temporalis and rectal temperatures were reduced by surface cooling to
32 degrees C (standard deviation, 0.1 degrees C) for 3, 6, and 12 hours (n = 10
for each time point) beginning 1 hour after cold-induced brain injury. RESULTS:
The apoptotic cells were detectable for up to 72 hours after the initial brain
injury and reached a peak at approximately 24 to 48 hours, with a mean peak value
of 24.29 +/- 5.26, 15.37 +/- 4.10, 15.81 +/- 3.56, 13.94 +/- 2.48, 10.46 +/-
2.23, and 7.68 +/- 2.48% in the cortex, subcortex, white matter, CA1, CA3, and
dentate gyrus, respectively, and had a significant increase, compared with the
control value (mean +/- standard error, P < 0.01). Agarose gel electrophoresis of
DNA extracted from cortex and hippocampus containing apoptotic cells revealed a
"DNA ladder" at 180- to 200-base pair intervals. In animals subjected to the same
brain injury that underwent 32 degrees C hypothermia, the numbers of apoptotic
cells were reduced evidently and DNA fragmentation was inhibited. CONCLUSION: The
data suggest that apoptosis occurs after cold-induced brain injury and that DNA
fragmentation may be associated with apoptotic cell death. Moderate hypothermia
shows specific effect on inhibition of apoptotic cell death and cellular DNA
fragmentation after cold-induced brain injury in rats.
PMID- 9657197
TI - Tamoxifen inhibits GH3 cell growth in culture via enhancement of apoptosis.
AB - OBJECTIVE: To investigate the antitumor effects of tamoxifen on pituitary tumor
GH3 cells, which lack receptors for dopamine. METHODS: GH3 cells were treated
with tamoxifen (10(-7) mol/L), bromocriptine (10(-8) mol/L), or a combination of
tamoxifen and bromocriptine in serum-free media. The cell number,
bromodeoxyuridine (BrdU) labeling ratio, and apoptotic ratio were assessed.
Prolactin (PRL) expression was examined using immunocytochemistry and Western
blot analysis. RESULTS: After tamoxifen treatment for 4 days, the cell number
decreased to 53.0% of that of untreated control cells. The percentage of PRL
immunoreactive GH3 cells decreased to 2.9%, versus 8.6% of untreated control
cells, which was compatible with the results of Western blot analysis for PRL.
Apoptosis increased to approximately three times that of untreated control cells
at Day 2 of treatment, whereas no significant change was shown in BrdU
incorporation. These effects by tamoxifen were not observed in the simultaneous
treatment with 17beta-estradiol. Bromocriptine did not change the cell number,
BrdU incorporation, the apoptotic ratio, or the percentage of PRL-positive cells,
and it was also shown that tamoxifen did not change the sensitivity of GH3 cells
to bromocriptine treatment. CONCLUSION: Tamoxifen, an antiestrogen, exerts its
antitumor effect on GH3 cells in two ways: by suppression of cell growth and by
causing a decrease in PRL. Apoptosis seems to contribute to the inhibition of GH3
cell growth.
PMID- 9657198
TI - Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking
malignant glioma growth.
AB - OBJECTIVE: Preliminary studies have demonstrated that the Ras family and related
guanosine 5'-triphosphate-dependent proteins (G-proteins) are overactivated in
malignant gliomas and may function as indirect mediators of glial transformation
initiated by deregulated upstream signaling elements. We postulated that
inhibiting the activation of such proteins might represent a promising strategy
for blocking the aberrant proliferation of these tumors. METHODS AND RESULTS:
Accordingly, we examined the therapeutic efficacy against malignant glioma cells
in vitro of a series of selective peptidomimetic inhibitors of farnesylation (FTI
277) and geranylgeranylation (GGTI-286 and GGTI-298), which are critical steps in
the post-translational processing (prenylation) of these proteins. We first
defined concentration-response relationships for each of these agents, using MTS
based cell proliferation assays in the established malignant glioma cell lines U
87 and LN-Z308 and the low-passage malignant glioma cell line SG-388. FTI-277,
GGTI-286, and GGTI-298 each produced a striking concentration-dependent
antiproliferative effect on the glioma cell lines, with the median effective dose
ranging from 2.5 to 15.5 micromol/L. We then assessed the effect of prenylation
inhibition on cell viability using clonogenic growth assays. This demonstrated a
steady drop in the number of colonies with increasing drug concentrations for all
three inhibitors. Third, we examined whether the cytotoxic effects of one of
these inhibitors (GGTI-298) were associated with the induction of apoptosis using
a terminal transferase-catalyzed in situ end-labeling technique. This approach
showed a time-dependent increase in apoptotic cell numbers, which correlated with
a progressive decrease in the percentage of cells that were viable as assessed by
trypan blue exclusion. CONCLUSION: Our studies demonstrated that FTI-277, GGTI
286, and GGTI-298 each yielded significant antiproliferative effects in human
malignant glioma cells in vitro at low micromolar concentrations, which have been
achievable in vivo without major systemic toxicity. Extended periods of drug
treatment produced cytotoxicity in the tumor cells, which correlated with the
induction of apoptosis. We conclude that inhibition of Ras and related G-proteins
offers a promising approach for blocking glioma proliferation that justifies
further investigation in vivo.
PMID- 9657199
TI - Neurosurgery at the University of Virginia.
AB - Before 1937, members of the Department of Surgery and Gynecology practiced
emergency neurosurgery at the University of Virginia in the same fashion as in
other hospitals in the United States. In 1937, Claude C. Coleman, Chairman of the
Department of Neurosurgery at the Medical College of Virginia in Richmond,
organized a Division of Neurosurgery as part of the Department of Surgery and
Gynecology at the University of Virginia. He designated one of his staff members,
John M. Meredith, as Neurosurgeon-in-charge. Dr. Coleman served as Clinical
Professor of Neurological Surgery at the University of Virginia from 1937 to
1941, while also working in Richmond. This arrangement attracted increasing
numbers of patients, leading to the formation of a separate department, under the
direction of William Gayle Crutchfield, in 1941. In conjunction with Juan de Dios
Martinez-Galindo, who joined the faculty in 1943, Dr. Crutchfield built and
directed the neurosurgical training program until his retirement. In 1969, John
A. Jane, Sr., became Professor and Chairman of the Department of Neurosurgery.
Pursuing the Jeffersonian intent of attracting "... those of due degree of
science and of talents for instruction," the Department has been enhanced by the
arrival of Neal F. Kassell in 1984, Ladislau Steiner in 1987, Edward R. Laws,
Jr., in 1992, Dheerendra Prasad in 1995, Gregory Helm in 1996, and Mark Shaffrey
in 1997. Resident training has been a priority of the Department of Neurosurgery;
many academic neurosurgeons were trained and practiced their specialty in the
Department early in their careers. Sixty years after its foundation, the
Department of Neurosurgery continues its commitment to patient care, research,
and the "... instruction of those who come after us."
PMID- 9657200
TI - Perspectives on neurosurgical practice: neurosurgery in Jordan.
AB - Neurosurgery as a specialty medical field is new in Jordan. This article
documents the history, current status, and projected future of neurosurgery in
Jordan. Resident training is also highlighted, and challenges for the future of
the profession are presented.
PMID- 9657201
TI - Granulomatous hypophysitis caused by a ruptured intrasellar Rathke's cleft cyst:
report of a case and review of the literature.
AB - OBJECTIVE AND IMPORTANCE: Ruptured Rathke's cleft cyst is a rare cause of giant
cell granulomatous hypophysitis. Chronic inflammatory reaction is caused by
extravased cyst content into the adjacent gland. We provide a demonstration that
mucins produced by cells lining the cyst wall caused the granulomatous giant cell
reaction. CLINICAL PRESENTATION: A 37-year-old nonpregnant woman presented with a
3-year-history of headache and amenorrhea. She had experienced normal sexual
maturation, and her medical history was unremarkable. Radiologically, the lesion
appeared as an intrasellar mass with a cystic component indistinguishable from a
pituitary adenoma with cystic degeneration. TECHNIQUE: The patient underwent a
transsphenoidal approach. Because no demarcation between normal and affected
tissue was evident at surgery, the lesion and residual pituitary were radically
removed. Tissue was studied using routine hematoxylin and eosin and histochemical
stainings for mucins and immunocytochemical techniques. CONCLUSION: This study
demonstrates that mucins that had spilled out from the cyst caused the
granulomatous reaction. Using computed tomography, magnetic resonance imaging,
and gross inspection, distinction between granulomatous hypophysitis and
pituitary adenoma was virtually impossible. Nevertheless, a granulomatous
reaction of the pituitary gland should be suspected in a case of a sellar mass
having a cystic area. In such cases, intraoperatory diagnosis on frozen sections
is mandatory because adoption of a conservative treatment allows preservation of
the gland.
PMID- 9657202
TI - Spontaneous shrinkage of lumbosacral lipoma in conjunction with a general
decrease in body fat: case report.
AB - OBJECTIVE AND IMPORTANCE: We describe a rare case of a lumbosacral lipoma that
shrank spontaneously in parallel to a general loss of body fat. Although early
prophylactic surgery is generally recommended for lumbosacral lipomas, the
observation made in this case may provide an important implication regarding the
conservative management of this disorder. CLINICAL PRESENTATION: A 9-year-old
male patient with a subcutaneous lipoma at the sacral level was found to have a
lumbosacral lipoma in the spinal canal and tethered spinal cord, as revealed by
magnetic resonance imaging. The patient showed no neurological or urological
deficits, except for a mild pes cavus deformity. INTERVENTION: Follow-up magnetic
resonance imaging performed 4 years later revealed a significant decrease in the
size of the lumbosacral lipoma. The patient became very thin and showed no
neurological deterioration during the follow-up period. The shrinkage of the
lipoma was considered to be in association with the general loss of body fat.
CONCLUSION: The control of body weight may be an important factor in the
conservative management of patients with lumbosacral spinal lipomas.
PMID- 9657203
TI - Delayed posttraumatic middle cerebral artery vasospasm demonstrated by magnetic
resonance angiography: case report.
AB - OBJECTIVE AND IMPORTANCE: Magnetic resonance (MR) angiographic diagnosis is a
noninvasive method having high sensitivity and specificity in the detection of
various cerebrovascular disorders. This is the first report of MR angiographic
detection of delayed posttraumatic middle cerebral artery vasospasm, the
occurrence of which has been rarely described. CLINICAL PRESENTATION: A 42-year
old man sustained head trauma in a traffic accident, which caused a right
subdural hematoma. Even though the hematoma was irrigated through one burr hole
on Day 10, the patient subsequently developed left hemiparesis in association
with dysarthria 4 days after surgery. MR angiography demonstrated decreased flow
signal in the right M1 and M2 portions, suggestive of vasospasm. INTERVENTION:
The patient underwent intravascular volume expansion/ hemodilution therapy for 3
days. CONCLUSION: After the therapy, the ischemic symptoms completely
disappeared. Follow-up study confirmed resolution of the flow signal in the right
middle cerebral artery. It is suggested that MR angiography is a useful
noninvasive method in the evaluation of posttraumatic cerebrovascular disorders,
which constitute important secondary insults in head trauma.
PMID- 9657204
TI - Diagnosis and monitoring of cerebral hyperfusion after carotid endarterectomy
with single photon emission computed tomography: case report.
AB - OBJECTIVE AND IMPORTANCE: Focal neurological deficits after carotid
endarterectomy may result from ischemia or hyperperfusion. The usefulness of
single photon emission computed tomography (SPECT) for differentiating between
these two mechanisms has not been previously emphasized. CLINICAL PRESENTATION:
An 83-year-old man experienced dysarthria and left-sided weakness immediately
after undergoing endarterectomy of the right internal carotid artery. The results
of computed tomography of the head were normal, and transcranial Doppler
sonography showed symmetrically elevated velocities in both middle cerebral
arteries. On the 1st postoperative day, the patient's deficits worsened in
parallel with spontaneous increases in blood pressure, and blood pressure
reduction with labetalol resulted in clinical improvement. INTERVENTION: On the
2nd postoperative day, technetium-99-hexametazime SPECT demonstrated markedly
increased flow in the right basal ganglia and inferior frontal cortex, confirming
the diagnosis of cerebral hyperperfusion. The patient's deficits continued to
improve with antihypertensive therapy, and SPECT performed 7 and 48 days after
surgery showed gradual normalization of the focal hyperemia. CONCLUSION: SPECT
can be used to diagnose and monitor cerebral hyperperfusion after carotid
endarterectomy and may be of particular value for differentiating hyperperfusion
from ischemia when characteristic computed tomographic and transcranial Doppler
sonographic findings are absent.
PMID- 9657205
TI - Nontraumatic atlanto-occipital and atlantoaxial rotatory subluxation: case
report.
AB - OBJECTIVE AND IMPORTANCE: Concomitant atlantoaxial and atlanto-occipital
subluxation resulting from any cause is extremely rare. We have found only five
previously reported cases and describe another, suggesting a treatment plan.
CLINICAL PRESENTATION: A 13-year-old female patient presented with a 3-month
history of neck pain and decreased neck movements. All symptoms started after a
localized neck infection had been treated successfully with antibiotics. There
was no history of trauma. A diagnosis of postinfective atlanto-occipital and
atlantoaxial rotatory subluxation was made based on a plain roentgenogram and was
confirmed based on a computed tomographic scan. INTERVENTION: The atlantoaxial
and atlanto-occipital subluxation was reduced during surgery. A posterior C1-C2
fixation was performed, and the atlanto-occipital joint was stabilized by means
of a halo body jacket for 3 months. One year after removal of the jacket, all
subluxation remained reduced and the patient retained significant neck movement.
CONCLUSION: Disruption of the occipito-atlanto-axial complex can result from
relatively minor head and neck infections and should be suspected in children
with persisting neck pain and decreased neck movements. It may not be necessary
to perform an occipitoaxial fusion to treat these patients, and a more limited
fusion may be successful.
PMID- 9657206
TI - Distal posterior cerebral artery revascularization in multimodality management of
complex peripheral posterior cerebral artery aneurysms: technical case report.
AB - OBJECTIVES AND IMPORTANCE: Although controversial, revascularization of the
distal posterior cerebral artery (PCA) may become necessary in treating complex
PCA aneurysms before proximal parent vessel sacrifice. The revascularization of
the distal PCA territories of two patients with peripheral PCA aneurysms is
presented. CLINICAL PRESENTATIONS: One patient had an aneurysm of the P2-P3
segment and failed a selective P2 balloon occlusion test by developing homonymous
hemianopia before planned parent vessel sacrifice. The other patient with a giant
P2 segment aneurysm presented with visual field deficits. TECHNIQUE: The distal
segment of PCA was revascularized before the aneurysms were trapped by surgical
clipping or coil occlusion of the distal P2 segment, proximal to the aneurysms.
In both cases, the occipital artery was used as the "donor" vessel. Temporary
occlusion times were 22 and 20 minutes, respectively. Both grafts were patent on
postoperative angiography, and both patients had full visual fields at the time
of their follow-up examinations. CONCLUSION: De novo distal P2 sacrifice,
advocated for treating peripheral PCA aneurysms, leads to visual field deficits
in some patients. Revascularization of the distal segment of the PCA, less
technically demanding than bypass to other PCA segments, preserves blood flow,
thus sparing vision in this subset of patients.
PMID- 9657207
TI - Surgical removal of a choroid plexus adenoma using the argon beam coagulator:
technical case report.
AB - OBJECTIVE AND IMPORTANCE: Choroid plexus tumors may be extremely vascular,
limiting surgical resection. A case of a choroid plexus adenoma is presented in
which the argon beam coagulator (System 6500; ConMed Corp., Utica, NY) was used
as a surgical adjunct. CLINICAL PRESENTATION: A 12-year-old male patient with a
giant tumor of the lateral ventricle presented with visual loss and was found to
have a large intraventricular tumor. At surgery, the tumor was extremely
vascular, and the pathological finding was consistent with a choroid plexus
adenoma. TECHNIQUE: Because of its vascularity, the tumor was resected in stages
with the aid of the argon beam coagulator. CONCLUSION: We conclude that this
device may have application in selected neurosurgical operations.
PMID- 9657208
TI - Stereotactic ventriculoperitoneal shunt for idiopathic intracranial hypertension:
technical note.
AB - OBJECTIVE: Lumboperitoneal shunting is the bastion of neurosurgical management
for idiopathic intracranial hypertension (IIH). However, recent studies document
a high failure rate for this procedure. The present study was designed to explore
the feasibility of placing ventriculoperitoneal shunts under stereotactic control
into patients with IIH as an alternative to lumboperitoneal shunting. METHODS:
Seven patients with IIH for whom medical management had failed underwent
stereotactic implantation of ventriculoperitoneal shunts. RESULTS: Shunt
placement was successful and uncomplicated in each case. Five of seven patients
experienced complete resolution of papilledema. The remaining two patients showed
resolving papilledema. Six of seven patients experienced resolution of headache.
The remaining patient continued to have headaches despite a radionuclide study
demonstrating normal shunt function. CONCLUSION: Our results suggest that
stereotactic ventriculoperitoneal shunting may be a reasonable alternative to
lumboperitoneal shunting in those patients with IIH who require surgical
intervention.
PMID- 9657209
TI - Library: historical perspective. John Farquhar Fulton.
PMID- 9657210
TI - John Farquhar Fulton.
PMID- 9657211
TI - Intramedullary pressure in syringomyelia: clinical and pathophysiological
correlates of syrinx distension.
PMID- 9657212
TI - Risk factors for neurosurgical site infections after craniotomy: a prospective
multicenter study of 2944 patients.
PMID- 9657213
TI - Profiling of the eye aqueous humor in exfoliation syndrome by high-performance
liquid chromatographic analysis of hyaluronan and galactosaminoglycans.
AB - The concentrations of hyaluronan and galactosaminoglycans -- i.e., chondroitin
sulfate and dermatan sulfate -- were measured in the aqueous humor of the eye
from patients with exfoliation syndrome and from healthy persons. The
glycosaminoglycans/proteoglycans were almost completely precipitated (>97%) with
ethanol in the presence of dextran as carrier and, following enzymic digestion,
hyaluronan and galactosaminoglycans, were quantitatively converted to delta4,5
disaccharides. Non-degraded heparan sulfate and proteins/glycoproteins were
removed by ultrafiltration using a Centricon 3 membrane. Separation and
determination of hyaluronan- and galactosaminoglycan-derived delta-disaccharides
were performed by ion-suppression HPLC. For an accurate analysis in triplicate,
as little as 50 microl of aqueous humor is required. Application of this method
to the analysis of samples from six patients with exfoliation syndrome and three
healthy persons showed that hyaluronan levels in patients (6.65-16.15 microg ml(
1)) were significantly higher (3-8 times) than in healthy persons (2.0-2.24
microg ml(-1)). There was no significant alteration in the galactosaminoglycan
concentration. The obtained data open a new area in the deeper understanding of
the exfoliation syndrome pathophysiology and in establishing a highly sensitivity
and accurate HPLC method for its diagnosis and patient's follow-up.
PMID- 9657214
TI - Quantitative detection method of triglycerides in serum lipoproteins and serum
free glycerol by high-performance liquid chromatography.
AB - We have developed a simple and reliable method for quantitative detection of
triglycerides (TG) in serum lipoproteins and serum-free glycerol (FG) by high
performance liquid chromatography (HPLC). After separation of serum constituents
using a new gel-permeation column (TSK gel Lipopropak XL, Tosoh) and a new eluent
(TSK eluent LP-2, Tosoh), TG and FG were detected by on-line reaction using a
modified reagent which contained glycerol kinase, glycerol-3-phosphate oxidase
and lipoprotein lipase. HPLC patterns showed five peaks corresponding to
chylomicrons, very-low-density, low-density, high-density lipoproteins and FG.
Absolute concentrations of TG in each lipoprotein fraction and serum FG were
calculated from the corresponding peak areas using standard FG as a calibrator.
Due to its very high sensitivity of peak detection, this method has become
desirable for the analyses of lipoproteins of very low concentrations such as in
cell culture systems. This technique will contribute to a better understanding of
lipoprotein TG and serum FG distribution in human and nonhuman subjects.
PMID- 9657215
TI - Salt-independent binding of antibodies from human serum to thiophilic
heterocyclic ligands.
AB - Several thiophilic adsorbents with mercaptoheterocyclic ligands have been
analyzed for their ability to bind human serum proteins in a salt-independent
way. In contrast to 2-mercaptopyrimidine, 2-mercaptopyridine derived ligands show
a group-selective binding of immunoglobulins and alpha2-macroglobulin, not only
in the presence of high concentrations of sodium sulphate but in buffers with low
ionic strength. The binding is restricted to thiophilic gels obtained by coupling
2-mercaptopyridine to a vinylsulphone-activated matrix and is not achieved on
epichlorohydrin-activated gels. A novel thiophilic ligand based on
mercaptonicotinic acid, containing a carboxylic group together with the
thiophilic pattern of thioaromatic adsorbents, is demonstrated to be useful as an
alternative purification scheme for antibodies.
PMID- 9657216
TI - Validation procedures of sedimentation field-flow fractionation techniques for
biological applications.
AB - Sedimentation field-flow fractionation (SdFFF) offers great potential for the
separation of submicrometer and micrometer-sized species. The availability of
commercial instrumentation and the versatility of this method originated its
success. At this stage of development, SdFFF techniques are mature enough for use
in analytical research, development and even routine work. However, prior to
their use, these techniques like any other methodologies, have to be validated.
As the application of SdFFF techniques to cell separation is being constantly
developed, we have investigated separation performance according to validation
rules classically defined for separation methods (chromatography) in the case of
cellular materials.
PMID- 9657217
TI - Identification of a flunixin metabolite in camel by gas chromatography-mass
spectrometry.
AB - A flunixin metabolite, a hydroxylated product, has been identified in camel urine
and plasma samples using gas chromatography-mass spectrometry (GC-MS) and GC-MS
MS in the electron impact and chemical ionization modes. Its major fragmentation
pattern has been verified by GC-MS-MS in daughter ion and parent ion scan modes.
The method could detect flunixin and its metabolite in camel urine after a single
intravenous dose of 2.2 mg of flunixin/kg body weight for 96 and 48 h,
respectively, which increases the reliability of antidoping control analysis.
PMID- 9657218
TI - Effect of temperature and some common metals on the stability of volatile
anaesthetic-Entonox mixtures.
AB - Thermal stability of pressurised ready-to-use volatile liquid anaesthetic
mixtures (halothane, isoflurane and enflurane) in Entonox (commercially available
premixed 50% N2O, 50% O2 mixture) were investigated at temperatures of 20, 258,
400, 503 and 602 degrees C on glass, stainless steel, copper and aluminium by gas
chromatography and GC-MS. It was found that most of the decomposition products
formed were halogenated compounds and the observed thermal stabilities in glass,
stainless steel and copper allowed a thermal treatment up to 250 degrees C
without any decomposition problem. Aluminium was found to be the most effective
metal at causing decomposition of the anaesthetic mixtures even at lower
temperatures.
PMID- 9657219
TI - Simple analysis of local anaesthetics in human blood using headspace solid-phase
microextraction and gas chromatography-mass spectrometry-electron impact
ionization selected ion monitoring.
AB - A simple method for analysis of five local anaesthetics in blood was developed
using headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass
spectrometry-electron impact ionization selected ion monitoring (GC-MS-EI-SIM).
Deuterated lidocaine (d10-lidocaine) was synthesized and used as a desirable
internal standard (I.S.). A vial containing a blood sample, 5 M sodium hydroxide
and d10-lidocaine (I.S.) was heated at 120 degrees C. The extraction fiber of the
SPME system was exposed for 45 min in the headspace of the vial. The compounds
adsorbed on the fiber were desorbed by exposing the fiber in the injection port
of a GC-MS system. The calibration curves showed linearity in the range of 0.1-20
microg/g for lidocaine and mepivacaine, 0.5-20 microg/g for bupivacaine and 1-20
microg/g for prilocaine in blood. No interfering substances were found, and the
time for analysis was 65 min for one sample. In addition, this proposed method
was applied to a medico-legal case where the cause of death was suspected to be
acute local anaesthetics poisoning. Mepivacaine was detected in the left and
right heart blood samples of the victim at concentrations of 18.6 and 15.8
microg/g, respectively.
PMID- 9657220
TI - Gas chromatography-mass spectrometric method for quantitative determination in
human urine of dicarboxylic (dioic) acids produced in the body as a consequence
of cholesterol biosynthesis inhibition.
AB - A capillary gas chromatography-mass spectrometric (GC-MS) method in human urine
has been developed and validated for the quantitative determination of
dicarboxylic acids (dioic acids) which are produced in the body as a consequence
of the administration of an inhibitor of the enzyme squalene synthase, which is
involved in the biosynthesis of cholesterol. The standards and quality control
(QC) samples were prepared by adding dioic acids into human urine. Internal
standard (sebacic acid) was added to each urine sample (0.1 ml) and then dried by
evaporation under nitrogen. The dried sample was reacted with pentafluorobenzyl
(PFB) bromide under conditions that maximized the formation of the di-PFB ester
(at the expense of the mono-PFB ester) of the dioic acids. After drying by
evaporation, each sample residue was reconstituted in mesitylene and injected
into a capillary GC-MS system via a splitless injection. The detection was by
negative ion chemical ionization mass spectrometry with selected ion monitoring
(SIM) of the [M-PFB]- of the analytes and the internal standard.
PMID- 9657221
TI - Use of generic fast gradient liquid chromatography-tandem mass spectroscopy in
quantitative bioanalysis.
AB - Short narrow analytical HPLC columns have been used successfully with high linear
flow-rates and combined with mass spectrometric detection to produce a generic
approach to quantitative bioanalysis. The approach has been used to validate
several assays in the low ng/ml region and an example is given in this paper.
When combined with a simple solid-phase extraction process the need for
complicated, time consuming method development has been removed for the majority
of pharmaceutical compounds. The approach takes advantage of not only the extra
selectivity of the MS-MS detector but the excellent resolution and peak shape
produced by gradient elution.
PMID- 9657222
TI - Quantitation of psilocin in human plasma by high-performance liquid
chromatography and electrochemical detection: comparison of liquid-liquid
extraction with automated on-line solid-phase extraction.
AB - Two modifications of the HPLC-ED method with respect to extraction procedure used
have been developed for psilocin, the active metabolite of psilocybin, in human
plasma using either liquid-liquid extraction (LLE) or automated on-line solid
phase extraction (on-line SPE). Each type of the sample preparation required a
different HPLC system followed by electrochemical detection at 650 to 675 mV. The
limit of quantitation of both modifications was 10 ng/ml psilocin. There was no
significant difference observable between the LLE and the on-line SPE in terms of
method standard deviation (LLE 1.82%, on-line SPE 1.13%) and the analytical
results. However, the advantages of on-line SPE in addition to different
selectivity were less manual effort, smaller plasma volumes of 400 microl (LLE 2
ml) and a recovery of psilocin in human plasma of nearly 100% (LLE 88%). In
contrast to a previous procedure both methods were rapid, simple and reliable and
yielded high plasma recoveries. They were used successfully in the quantitation
of psilocin in plasma samples obtained from healthy volunteers after p.o.
administration of 0.2 mg psilocybin per kg body mass. Plasma concentration curves
and pharmacokinetic parameters were calculated.
PMID- 9657223
TI - Achiral and chiral high-performance liquid chromatographic methods for
clinafloxacin, a fluoroquinolone antibacterial, in human plasma.
AB - Achiral and chiral HPLC methods were developed for clinafloxacin, a quinolone
antimicrobial agent. For achiral assay, analytes were isolated from plasma by
precipitating plasma proteins. Separation was achieved on a C18 column using an
isocratic eluent of ion pairing solution-acetonitrile (80:20, v/v) at 1.0 ml/min
with UV detection at 340 nm. The ion pairing solution was 0.05 M citric acid,
1.15 mM tetrabutylammonium hydroxide and 0.1% ammonium perchlorate. Inter-assay
accuracy was within 4.9% with an inter-assay precision of 3.7% over a
quantitation range of 0.025 to 10.0 microg/ml. For chiral assay, analytes were
isolated from plasma by solid-phase extraction. Separation was achieved on a
Crownpak CR(+) column using an isocratic eluent of water-methanol (88:12, v/v)
containing 0.1 mM decylamine at 1.0 ml/min with UV detection at 340 nm.
Perchloric acid was added to adjust pH to 2. Inter-assay accuracy was within 3.5%
with a inter-assay precision of 5.4% over a quantitation range of 0.040 to 2.5
microg/ml.
PMID- 9657224
TI - Simultaneous determination of albendazole sulfoxide enantiomers and albendazole
sulfone in plasma.
AB - A high-performance liquid chromatographic method has been developed for the
simultaneous determination of albendazole sulfoxide (ABZSO) enantiomers and
albendazole sulfone (ABZSO2) in human plasma. The resolution of ABZSO enantiomers
and ABZSO2 was obtained on a Chiralpak AD column using hexane-isopropanol-ethanol
(81:14.25:4.75, v/v/v) as the mobile phase. The drugs were detected by
fluorescence (lambda(exc) = 280 nm, lambda(em) = 320 nm). The drugs were
extracted from 500 microl plasma with ethyl acetate, and after solvent
evaporation, the residues were dissolved in the mobile phase and chromatographed.
The method was precise and accurate for the three compounds, as judged by the
coefficients of variation and relative errors observed. Linear standard curves
were obtained in the concentration range of 5-2500 ng/ml for ABZSO enantiomers
and 1-500 ng/ml for ABZSO2. A typical plasma concentration-time profile is
presented for one patient under treatment for neurocysticercosis.
PMID- 9657225
TI - Assay of paclitaxel (Taxol) in plasma and urine by high-performance liquid
chromatography.
AB - A new, rapid and sensitive high-performance liquid chromatographic method for the
analysis of paclitaxel (Taxol) in human plasma and urine was developed and
validated. After addition of an internal standard, paclitaxel was extracted from
plasma or urine by a liquid-liquid extraction using diethyl ether. Extraction
efficiency averaged 90%. Chromatography was performed isocratically on a reversed
phase column monitored at 227 nm. Retention times were 7.7 and 6.7 min for
paclitaxel and docetaxel, respectively, and the assay was linear in the range 25
1000 ng/ml. The limits of quantification for paclitaxel were 25 and 40 ng/ml in
plasma and urine, respectively. The assay was shown to be suitable for
pharmacokinetic studies of children involved in a phase I clinical trial.
PMID- 9657226
TI - Simultaneous high-performance liquid chromatographic determination of a
glucuronyl prodrug of doxorubicin, doxorubicin and its metabolites in human lung
tissue.
AB - A rapid and sensitive method was developed for the simultaneous determination of
the new doxorubicin glucuronide prodrug HMR 1826, the parent drug doxorubicin and
its metabolites in human lung tissue samples. Homogenization of frozen tissue
samples with the micro-dismembrator was followed by a silver nitrate
precipitation step. By removing the exceeding silver ions with sodium chloride
further purification steps could be omitted. Compounds were separated by
isocratic high-performance liquid chromatography on a LiChrospher 100 RP18 column
and a mobile phase consisting of citric acid buffer-acetonitrile-methanol
tetrahydrofuran within 30 min and quantified with fluorescence detection. The
method showed good recoveries for all compounds (86-99%) and a linear calibration
range of 20 ng/g-80 microg/g for doxorubicin and 1-600 microg/g for HMR 1826.
PMID- 9657227
TI - Determination of polyamines in human prostate by high-performance liquid
chromatography with fluorescence detection.
AB - A high-performance liquid chromatographic method for the determination of
polyamines in human prostate has been developed. This method is based on pre
column derivatization with dansyl chloride (Dns-Cl). The derivatives were
separated on a muBondapak C18 column (250x4.6 mm I.D.; 10 microm), and eluted
with methanol and distilled water using a one-step linear gradient. The column
eluate was monitored by fluorescence detection (excitation, 370 nm; emission, 506
nm). The within-assay precision of the study (C.V.) was as follows: putrescine
(PUT) 2.88%, spermidine (SPD) 2.94% and spermine (SP) 1.17%. The between-assay
precision (C.V.) was: PUT 2.66%, SPD 3.06%, SP 2.79%. The recovery was greater
than 97%. The detection limit for PUT, SPD and SP were 0.05, 0.08 and 0.06
nmol/ml, respectively. In contrast to other studies, sample or polyamine
derivatives did not require extraction with an organic solvent such as ethanol,
evaporation under vacuum or other condensation procedures. This is a simple,
rapid and sensitive method that can be applied to the determination of polyamines
in nearly all biological tissues and body fluids, such as urine and serum.
PMID- 9657228
TI - One-step purification of proteins from chicken egg white using counter-current
chromatography.
AB - Proteins present in chicken egg white are separated by counter-current
chromatography (CCC) in one step using a cross-axis coil planet centrifuge (X
axis CPC). The separation was performed with an aqueous polymer two-phase system
composed of 16% (w/w) poly(ethylene glycol) 1000 and 12.5% (w/w) dibasic
potassium phosphate by eluting the lower phase at a flow-rate of 1.0 ml/min. From
about 20 g of the crude egg white solution, lysozyme, ovalbumin, and
ovotransferrin were resolved within 5.5 h. Each component was identified by 12%
SDS gel electrophoresis with Coomassie brilliant blue staining.
PMID- 9657229
TI - In situ evaluation of esterase stereoselectivity in two-dimensional
electropherograms and tissue sections.
AB - Staining with both enantiomers of an alpha-naphthyl ester plus a diazonium salt
and comparing the color intensities given by the two enantiomers is a convenient
method to evaluate the esterase stereoselectivity for that ester in two
dimensional electropherograms and tissue sections. Application of this method for
rat liver has shown that (1) several esterases, e.g., one of pI 6.4 and Mr 118
kDa, are moderately stereoselective against alpha-naphthyl (R)-N-acetylalaninate
and (R)-N-methoxycarbonylalaninate but strictly stereoselective against alpha
naphthyl (S)-N-methoxycarbonylvalinate, implying that esterase stereoselectivity
may be inverted by changing the ester structure; and (2) these esterases are
mainly contained in the hepatocytes around central veins.
PMID- 9657230
TI - Determination of indomethacin residues in poultry by high-performance liquid
chromatography.
AB - A HPLC method using a C18 column and UV detection (254 nm) is described for the
determination of indomethacin residues in chicken tissues (liver, muscle and
fat). Drug extraction from tissue homogenate in phosphate buffer (pH 3.5) was
performed with dichloromethane. Mobile phase was acetonitrile-acetic acid (0.5%
in water) (50:50). Indomethacin detection limit was 20 ng/g for the studied
tissues. After administration of an oral dose of indomethacin (2 mg/kg), only
three of the eight poultry studied showed drug tissue levels, in those cases the
levels were below 50 ng/g.
PMID- 9657231
TI - Improved high-performance liquid chromatographic analysis of teniposide in human
plasma.
AB - A simple and practical high-performance liquid chromatographic analysis has been
developed for measuring teniposide (VM26) in human plasma. The present analytical
method has improved extraction efficiency from human plasma, therefore allowing
determination of VM26 in a clinical setting using ultraviolet detection alone.
Furthermore, sample preparation was simplified and shortened through use of a one
step extraction procedure. VM26 and internal standard (ibuprofen) were extracted
from human plasma (0.5 ml) with ethyl acetate. A phenyl muBondapak column eluted
with a mobile phase, consisting of acetonitrile-distilled water-acetic acid
(30:68:2, v/v/v) was used for separation, and quantitation was achieved with a UV
monitor set at 240 nm. Average extraction efficiency was 96.8+/-6.6% for VM26
between 1 and 25 microg/ml, and 91.4+/-4.3% for internal standard, with both
intra- and inter-day coefficients of variation being less than 10%. The detection
limit with a 100-microl injection was estimated at 0.2 microg/ml with a signal-to
noise ratio of 3 for VM26 in human plasma. The stability data of VM26 in plasma,
standard and stock solutions were also obtained. The present method was found to
be an alternative to the previously reported method with an electrochemical
detection, and can be easily applied to routine clinical pharmacokinetic studies
of VM26.
PMID- 9657232
TI - Selection of internal standard for quantitative analysis of enantiomers following
precolumn chiral derivatization.
PMID- 9657233
TI - Borna or not?
PMID- 9657234
TI - A viro-psycho-immunological disease-model of a subtype affective disorder.
AB - Borna Disease Virus (BDV) infections are widespread in animal species. This
neurotropic, negative and single-stranded enveloped RNA virus spreads via axonal
and transsynaptic pathways quite specifically into olfactoric and limbic
structures. The symptoms in BDV-infected animals range from unapparent or subtle
clinical manifestations to fatal neurological disorders. The severe and fulminant
course of the infection, which is often accompanied by neurobehavioral and
"emotional" disturbances, occurs sporadically and, at least in experimentally
infected animals (rats), is thought to be mediated by immunopathology. Increases
in serum-BDV antibodies have also been detected in neuropsychiatric patients. In
addition, viral antigen and viral RNA have been observed in acutely ill major
depressive patients, leading to the conclusion that BDV was causally related to
psychiatric disorders, in particular to affective disorders. A number of studies
have meanwhile furnished evidence of abnormal immune functions in mentally ill
patients. In addition, stress has been shown to decrease immune responses to
viral infections. On the basis of these findings it is hypothesized that human
BDV infection represents a co-factor in the development or course of psychiatric
diseases. Stress may cause immunosuppression and thus induce activation of
persisting BDV in the limbic system, resulting in an inflammatory reaction of
these structures. These neuropathological changes might influence the
serotonergic or dopaminergic neurotransmitter systems. In addition, a specific
affinity of BDV structural elements for aspartate and glutamate receptors in the
hippocampal formation might directly induce an imbalance of these transmitter
system interactions, causing affective and behavioral disturbances. The possible
interactions between stress-induced immunosuppression, BDV infection and
affective disorders in humans, and the theoretical and clinical aspects of this
concept are discussed.
PMID- 9657235
TI - The symmetry of symptom patterns in pre-post treatment designs.
AB - This article proposes a new nonparametric method for statistical evaluation of
clinical pre-post treatment designs. In clinical research, models of marginal
symmetry typically are estimated from log-linear models of axial and quasi
symmetry. As such, they provide overall goodness-of-fit information concerning
change in probabilities of categories of one variable that was observed twice.
This paper proposes the following three extensions: (1) using models of marginal
symmetry for changes in patterns of two or more variables, and (2) following up
global marginal symmetry tests using Lehmacher's sign tests. (3) To protect the
experiment-wise alpha, a modified Bonferroni-Holm procedure is proposed. The new
approach allows researchers to make statements about treatment effects at the
level of single symptoms. Examples illustrate application of all three symmetry
models and the follow-up test using data from pharmaco-psychiatry. The discussion
relates Lehmacher's tests to two-sample Configural Frequency Analysis of multi
discrimination types. Strategies of statistical significance testing are
presented and the importance of the proposed methodological approach for
psychiatric research is discussed.
PMID- 9657236
TI - Paroxetine: a review of clinical experience.
AB - The selective serotonin reuptake inhibitor paroxetine has been extensively
studied and is now an established therapy for the treatment of depressive
disorders. Paroxetine has demonstrated efficacy in major depression in both young
and elderly patients, with an improved tolerability profile over conventional
antidepressants. Paroxetine is effective across a continuum of anxiety and
depressive disorders, including severe depression, depression with anxiety,
comorbid depression and obsessive-compulsive disorder. The first agent of its
class licensed for use in panic disorder, paroxetine has been shown to be
effective in reducing the number of panic attacks and preventing relapse. A
worldwide clinical database has established that paroxetine has a benign adverse
event profile. Paroxetine therefore offers an effective and well tolerated
treatment for a broad spectrum of psychiatric disorders.
PMID- 9657237
TI - Plasma concentrations of risperidone and its 9-hydroxy metabolite and their
relationship to dose in schizophrenic patients: simultaneous determination by a
high performance liquid chromatography with electrochemical detection.
AB - A simple, sensitive and accurate method for the simultaneous determination of
risperidone (RSP) and its 9-hydroxy metabolite (9-OH-RSP) in human plasma is
described. The relationship between dose of RSP and the plasma concentration of
RSP and 9-OH-RSP in a clinical situation is discussed. Both compounds were
isolated from plasma by a simple one-step liquid-liquid extraction with 15%
methylene chloride in pentane. High-performance liquid chromatography separations
were made on a cyano column and the compounds were detected by electrochemical
detector. The method had sufficient sensitivity to determine RSP and 9-OH-RSP
accurately at concentrations as low as 0.25 ng/ml when 1 ml of plasma is used for
the analysis. The assay determinations were accurate, precise and consistent with
a coefficient of variation less than 15%. Commonly co-administered drugs and
other antipsychotics did not interfere with the analysis of either RSP or 9-OH
RSP There were large variations in inter- and intra-individual values of plasma
concentrations of RSP and 9-OH-RSP. The 9-OH-RSP appears to be the major
circulating active moiety and its plasma concentrations were, on the average 22
fold higher than that of RSP in schizophrenic patients treated with RSP. The
ratio of RSP/9-OH-RSP concentrations suggested that three of the patients may
have deficiency in cytochrome P450 enzyme CYP 2D6. The plasma concentrations of
RSP showed a weak relationship with the administered daily oral dose (r = 0.4684,
p = 0.01, n = 215). However, there was a good relationship between the daily dose
of RSP and the plasma concentration of 9-OH-RSP (r = 0.6654, p = 0.01, n = 280)
or the total active moiety, sum of RSP and 9-OH-RSP concentrations (r = 0.7041, p
= 0.0005, n = 280). The measurement of the total active moiety in plasma of
schizophrenic patients may be useful for assessing the relationship between dose
and plasma concentration and dose and clinical outcome of patients rather than
measuring RSP alone.
PMID- 9657238
TI - Lack of psychotomimetic or impairing effects on psychomotor performance of
acamprosate.
AB - The possible effects on psychomotor performance, concentration, attention, and
mood of acamprosate (calciumacetylhomotaurinate) were assessed using a
randomized, double-blind, cross-over, placebo-controlled design involving 12
healthy male volunteers. Acamprosate 2 g daily per os or placebo was administered
for seven days and separated by washout intervals of at least 21 days. Objective
tests evaluated psychomotor functions (simple reaction time measurement, binary
choice reaction test, computerized visual searching task, sustained attention
test). Mood was assessed using the Beck Depression Inventory and the Beschwerde
Liste to assess subjective physical impairment. Additionally, a visual 3-D
illusion paradigm was applied to measure the psychotomimetic effect. A dose of
acamprosate of 2 g/day for seven days was free of any significant effects on
mood, concentration, attention, psychomotor performance and did not produce any
subjective sedation, excitation or psychotomimetic effects.
PMID- 9657239
TI - Gastrointestinal side-effects after switch to generic valproic acid.
PMID- 9657240
TI - Abdominal Takayasu's aortitis, the middle aortic syndrome and atherosclerosis. A
critical review.
AB - To review the current status of clinical, pathological and arteriographic aspects
of abdominal Takayasu's aortitis (TA). Personal experience with 86 patients with
TA and review of the literature is the basis of this report. The diagnostic
significance of primary versus secondary atherosclerosis is described in this
communication and the arteriographic differential diagnostic guidelines are
provided to separate abdominal TA from abdominal atherosclerosis.
PMID- 9657241
TI - Intraoperative assessment of cerebral ischaemia during carotid surgery.
AB - BACKGROUND: This study aimed to evaluate the reliability of somatosensory evoked
potentials (SEPs) in identifying clamping ischaemia during carotid surgery under
general anaesthesia. METHODS: We reviewed the records of 196 consecutive carotid
endarterectomies (CEA) performed under general anaesthesia, out of 1550 patients
operated on between 1975 and 1993. SEPs were monitored after contralateral median
nerve stimulation at the wrist in all patients. Moreover they received an
intravenous bolus of 2500 IU of heparin and the stump pressure was measured. A
completion angiography was performed in all patients. An intraluminal shunt was
inserted when the amplitude of the N20-P25 SEPs complex decreased by more than
50% of pre-clamping value (pathologic SEPs) or when a preoperative CT-scan showed
an ischaemic area in the contralateral hemisphere. In some patients the shunt was
not inserted because of technical difficulties or because the pathological SEP
complex decrease developed when the suture of the arteriotomy was almost
complete. RESULTS AND CONCLUSIONS: As the preclamping amplitude (Ab) of N20-P25
was extremely variable, ranging from 0.9 and 7.5 microV, we adopted the ratio:
deltaA=(At-Ab)/Ab (At=amplitude measured during clamping every 2 min at time t).
Mean decrease of deltaA measured in the whole group ranged between 15% and 20%,
but mean deltaA values in patients with pathological SEPs were around 60%. Even
patients with positive CT-scans or with a back-pressure lower than 50 mmHg
developed a mean deltaA decrease of about 20%. A pathological SEP was present in
50 patients, but developed in only 12 during the clamping trial. An intraluminal
shunt was inserted in 22 cases; the other patients received pharmacological
treatment with anaesthetic or vasoactive drugs. Among the patients with
pathological SEPs, 3 presented postoperative symptoms related to carotid cross
clamping; only 1 of these was shunted but without SEPs normalisation. No patients
with normal SEPs developed a postoperative neurological deficit, giving a
reliability of 86.7%, a sensitivity of 100% and a specificity of 86.5%.
PMID- 9657242
TI - Carotid atherosclerosis in subjects with different hyperlipidaemia phenotypes.
AB - OBJECTIVE: To evaluate the presence of carotid plaque and/or stenosis in patients
with different phenotype of hyperlipidaemia. EXPERIMENTAL DESIGN: Case-control
study. SETTING: Outpatients metabolic clinic. PATIENTS: Sixty type IIa, 50 type
IIb and 40 type IV hyperlipidaemic subjects were compared with 50 normolipidaemic
controls, matched for sex and age. INTERVENTIONS: Blood lipid analysis for
phenotype classification was performed after two months of diet. Blood pressure
was measured by a zero-random sphygmomanometer. CHD risk factors, smoking habit,
previous and ongoing drug therapy were assessed by a self-administered
questionnaire. Echo-Doppler examination of the extracranial arteries (common,
internal and external carotid artery and bulb) was done by a Multigon Angioview
600 provided with a 7.5 MHz probe for B-mode and 5 MHz for pulsed Doppler.
Subjects were classified as having carotid atherosclerosis when a plaque and/or a
stenosis was found in at least one of the examined segments and as normal when no
atherosclerotic lesions were detected. RESULTS: There were more hypertensives
among type IV subjects whereas the prevalence of smokers and diabetics was
similar in all four groups. The prevalence of carotid atherosclerosis was higher
in type IIb and IIa subjects than in controls (58% and 38% respectively vs 14%,
p<0.01) while in type IV subjects it was comparable to that of controls (25%).
CONCLUSIONS: The present findings show that hypercholesterolaemia and mixed
hyperlipidaemia are frequently associated with carotid atherosclerosis, whereas
hypertriglyceridaemia is not. The role of hypertriglyceridaemia in the
development of atherosclerosis seems mediated by mechanisms other than plaque
formation.
PMID- 9657243
TI - Prevalence of morphological alterations in cervical vessels: a colour duplex
ultrasonographic study in a series of 3300 subjects.
AB - BACKGROUND: In order to define the morphological variants involved in carotid
elongation in terms of their clinical implications, we have analysed the
prevalence of morphological alterations in patients routinely subjected to
carotid colour duplex ultrasonography evaluation. METHODS: From January 1, 1993
to June 30, 1996, 3300 subjects were examined for central nervous system symptoms
(41% of cases) or for screening related to ischaemic heart disease, lower limb
arterial disease, hypertension or major dyslipidaemia (59% of cases). The chi(2)
test was used for statistical analysis. RESULTS: Morphological alterations
increased with age. While kinking was more prevalent in females (female:male
ratio 58% vs 42%), sharp kinking was significantly more frequent in males (39% vs
15%, p<0.001). Atheromatous plaques predominated in males (79% vs 46%, p<0.001),
as well as cases with haemodynamically significant involvement (16% vs 7%,
p<0.001). In patients with kinking there was a prevalence of haemodynamically
significant lesions (chi(2)=52.7, p<0.001). A possible link between
conformational abnormalities and hypertension appeared highly significant owing
to a very different prevalence of high blood pressure in the group of subjects
with kinking (chi(2)=239, p<0.001). We did not find a significant association
between major neurological symptoms and the presence of kinking (chi(2)=0.215,
p=0.643), but we found an association with transient ischaemic attacks
(chi(2)=6.9, p<0.01). CONCLUSIONS: Conformational abnormalities like kinking,
seem much more prevalent in subjects suffering from arterial hypertension. Even
though high blood pressure is an important risk factor for transient ischaemic
attacks, it is possible that the prevalence of atheromatous lesions and the flow
turbulence linked to kinking may also play a role in their pathophysiology.
PMID- 9657244
TI - Outcome after early treatment of popliteal artery aneurysms.
AB - BACKGROUND: Aneurysms of the popliteal artery are rare events with an estimated
incidence of 0.1-2.8%. Their clinical importance depends on their propensity to
cause thromboembolic complications or to rupture (18 to 31% of cases). This study
was designed to assess the advantages of elective treatment of asymptomatic
popliteal artery aneurysms so as to avoid the severe clinical manifestations that
eventually arise if they remain untreated. METHODS: From 1980 to 1995, in our
department we treated 28 popliteal aneurysms in 23 patients (19 elective
operations and 6 emergencies). Three of the aneurysms proved amenable to
fibrinolytic therapy alone. Follow-up lasted a mean 48 months (range 3 months to
15 years) in 20 patients (23 revascularizations). RESULTS: Global patency was
91.3%. Two thrombosed bypasses were treated by thrombolysis; in one case it did
not resolve the ischaemia and the leg was amputated. In one case only, a graft
became infected but this responded to conservative therapy with drainage and
antibiotics. CONCLUSIONS: These findings suggest that popliteal aneurysms with
good distal run-off should be repaired electively. Completely thrombosed
aneurysms with coexistent limb-threatening ischaemia should be treated initially
by thrombolysis. This will usually restore run-off and in some cases offers a
valid alternative to emergency surgery for limb salvage.
PMID- 9657245
TI - Factor G pathway reactive activity (GPRA) after surgery for abdominal aortic
aneurysm.
AB - BACKGROUND: Following major surgery, detection of endotoxaemia using the
Toxicolor (Limulus) test has been reported. In addition to endotoxins, this test
detects a reactant from human tissue, factor G pathway reactive activity (GPRA).
We measured endotoxin and GPRA in 10 patients during and after elective surgery
for abdominal aortic aneurysm. Additionally, we measured phosphokinase (CPK) and
GPRA levels in the muscle of 10 patients during abdominal aortic aneurysm surgery
and 6 during open laparotomy for other causes. METHODS: Samples were taken from
the arterial lines prior to surgery, before cross-clamping of the aorta,
immediately after and 1, 3, 6, and 18 hours after declamping. Muscle specimens
were taken from the rectus abdominus and homogenized in many levels. Endotoxin
concentrations were measured with the Endotoxin-Specific test. GPRA
concentrations were determined by subtracting the values from the Endotoxin
Specific test from those given by the Toxicolor test (Limulus assay with
achromogenic substrate). CPK was also measured. RESULTS: Endotoxin did not
significantly increase during or after surgery, but GPRA was elevated. GPRA in
muscle correlated significantly with CPK in muscle. CONCLUSIONS: We conclude that
GPRA was elevated after surgery, while endotoxin did not increase significantly.
The GPRA probably originated from human muscle tissue.
PMID- 9657246
TI - Decrease of platelet intracellular pH and adhesion by ticlopidine in patients
with vascular disease.
AB - BACKGROUND: Ticlopidine inhibits platelet aggregation by preventing the binding
of fibrinogen to its platelet receptor. We examined whether this inhibition
involved platelet transduction system such as Na+/H+ pump and platelet
intracellular calcium. METHODS: Platelet adhesion in 13 patients with peripheral
vascular disease treated with ticlopidine, 250 mg b.i.d for 30 days, was measured
in culture microplates before and after therapy. The microplate wells were coated
with human plasma, fibrinogen or collagen, and platelet adhesion was studied in
the resting condition and after stimulation with 1 and 10 microM ADP. At the same
time, platelet intracellular calcium and ADP-induced calcium increases were
measured with the fluorescent indicator Fura 2. In addition, intracellular pH and
thrombin-induced pH variations were measured with the fluorescent probe BCECF.
RESULTS: Platelet adhesion to plasma and fibrinogen was significantly reduced
(about 50%) after treatment with ticlopidine, while adhesion to collagen was not
modified. Basal calcium and ADP-induced calcium increase were not significantly
different before and after ticlopidine. Platelet basal intracellular pH was
reduced (from 7.44+/-0.009 to 7.41+/-0.017, p<0.05), but agonist-induced
alkalinisation was not significantly different. Early acidification, not
dependent on Na+/H+ exchange, was also reduced (p<0.05). CONCLUSIONS: These data
do not seem to support the hypothesis that ticlopidine-induced reduction of
platelet adhesion depends on alteration of the mechanisms determining signal
transduction, at least as far as basal and post-stimulation intracellular calcium
is concerned. On the contrary, the possibility that ticlopidine inhibits the
Na+/H+ antiport remains open to consideration.
PMID- 9657247
TI - Power-based colour coded duplex sonography for evaluation of calf veins.
AB - BACKGROUND: Power-based colour coded duplex sonography (PD) has been described to
display lower flow velocities compared to frequency-based colour coded duplex
sonography (CD). This study was undertaken to study the clinical usefulness of PD
in the evaluation of calf veins in suspected deep vein thrombosis. METHODS:
EXPERIMENTAL DESIGN: A prospective, comparative study. SETTING: University
hospital, Switzerland. PATIENTS AND MEASURES: CD of the complete deep venous
system and complementary PD of paired calf veins were performed in 50 consecutive
patients with clinically suspected DVT. All except three patients, with failed
vein puncture at the dorsum of the foot, had a venography used as reference test
for confirmatory diagnosis of DVT. RESULTS: Complete identification of calf veins
increased from 80.5% using CD to 97.9% using complementary PD (p=0.007). Overall
accuracy to detect an acute calf DVT was 96% (95% Ci, 85-99%) and 95% (95% CI, 83
99%), respectively. Accuracy was 95% (95% CI, 83-99%) using CD vs 94% (95% CI, 82
98%) using PD in posterior tibial, 87% (95% CI, 74-95%) vs 85% (95% CI, 71-94%)
in anterior tibial, and 95% (95% CI, 83-99%) vs 96% (95% CI, 85-99%) in peroneal
veins. Chronic post-thrombotic changes (10.6%) were more reliably recognized
using CD (accuracy 83% [95% CI, 72-94%]) compared to PD (accuracy 66% [95% CI, 59
85%]) due to tissue motion artifacts and inability to discriminate the direction
of blood flow. CONCLUSIONS: PD used complementary with CD is capable of
significantly improving identification of paired calf veins without loss of
diagnostic accuracy in the diagnosis of acute DVT.
PMID- 9657248
TI - Levels of the inhibitor of PMN-elastase in venous blood reflowing from
chronically affected veins: the role of venous stasis.
AB - BACKGROUND: Attention has recently been paid to the cell and biochemical
disorders involved in chronic venous insufficiency (CVI) and to their possible
relationship to the endothelium. METHODS: In the present study, carried out in 14
patients with CVI, we evaluated the levels of the inhibitor of elastase (I-EL)
generated by polymorphonucleate cells in the blood reflowing from affected
superficial veins of legs both at rest and after prolonged venous stasis (1 hour
in standing position). RESULTS: We evaluated the I-EL both as percentage of
activity (baseline 82.3+/-24.5%; after stasis 100.7+/-37.8%) and as absolute
values (0.67+/-0.26 U/ml; after stasis 0.79+/-0.39 U/ml). In blood samples taken
after venous stasis we found a tendency toward a trapping of white blood cells
and an increase of the haematocrit over baseline. The difference in the
percentages of activity of I-EL was statistically significant, but only a trend
was observed for the absolute values. CONCLUSIONS: We believe that the typical
haemodynamic disorders of patient with CVI increased by prolonged venous stasis
can modify the function of white blood cells, which are closely linked with
venous hypertension, thus playing an important role in the pathogenesis of skin
ulcers.
PMID- 9657249
TI - Importance of cutaneous postural reflex vasoconstriction in patients with
atherosclerotic occlusive disease of the lower extremities.
AB - OBJECTIVE: The present study was designed to measure the cutaneous postural
vasoconstrictive reflex (PVR) in normal controls and patients with
atherosclerotic occlusive disease of the lower extremities, and to determine its
diagnostic and prognostic relevance. EXPERIMENTAL DESIGN: The postural
vasoconstrictive reflex was recorded in 34 patients with atherosclerotic
occlusive disease of the lower limbs and 27 normal controls, using laser-Doppler
flowmetry. Patients also had ankle and toe pressure measurements and
transcutaneous oximetry (TcPO2). SETTING: University hospital. RESULTS: The PVR
on the pulp of the big toe was 20+/-7 arbitrary perfusion units in normal
controls, 9.4+/-12 in patients with claudication, and -19 +/- 5 in patients with
rest pain and/or gangrene, who differed from the claudicant and control groups
(p=0.001 and 0.0001 respectively). The sensitivity of negative PVR in the big toe
was 89% for the diagnosis of rest pain and/or gangrene, and its specificity, 83%.
The severity of foot ischaemia and PVR values exhibited a significant inverse
correlation (r=-0.56, p<0.0001). All patients with a poor outcome, ie. death
and/or major amputation within 100 days of follow-up, had a negative PVR, and all
patients with a positive PVR had a good 100-day prognosis without even a minor
amputation. CONCLUSIONS: Laser-Doppler provides useful additional information in
the assessment of foot ischaemia severity by showing that postural
vasoconstriction is impaired in patients with severe atherosclerotic occlusive
disease of the lower limbs, resulting in increased skin microcirculatory flow
during leg dependency.
PMID- 9657250
TI - Hyperselective renal artery embolisation in the treatment of post-traumatic
iatrogenic haematuria: report of two cases.
AB - Angiography and selective renal artery embolisation were performed in two
patients with post-traumatic iatrogenic kidney lesions and intractable
haematuria. One patient presented after a nephrolithotomy with rupture of a
segmental branch of the renal artery well demonstrated on selective angiography
which showed intraparenchymal extravasion of contrast medium. The other presented
after a renal biopsy with severe haematuria. Angiography performed 10 days later
demonstrated an arteriovenous fistula at the site of the puncture. Hyperselective
embolisation achieved immediate control of the haematuria in both patients, with
maximal preservation of the renal parenchyma and maintenance of good renal
function. At follow-up 12 months later, there had been no recurrence of the
haematuria. These results suggest that transcatheter embolisation should be
considered the method of first choice in renal trauma accompanied by intractable
haematuria before any surgery is attempted.
PMID- 9657251
TI - Anplag, a selective 5-HT2 receptor antagonist, reduces stenosis induced by
balloon injury in hypercholesterolaemic rabbit.
PMID- 9657252
TI - The inflammatory basis of trauma/shock-associated multiple organ failure.
AB - Multiple alterations in inflammatory and immunologic function have been
demonstrated in clinical and experimental situations after trauma and hemorrhage,
in particular the activation of various humoral (e.g. complement, coagulation)
and cellular systems (neutrophils, endothelial cells, macrophages). As a
consequence of this activation process there is synthesis, expression and release
of numerous mediators (toxic oxygen species, proteolytic enzymes, adherence
molecules, cytokines), which may produce a generalized inflammation and tissue
damage in the body. Mediators are responsible for ongoing interactions of
different cell types and for amplification effects through their networks and
feedback cycles, finally leading to a sustained inflammation and multiple organ
damage in the body. In the setting of trauma/shock, many activators including
bacterial as well as non-bacterial factors may be present that will induce local
and systemic inflammatory responses. Although the potential role of
bacteria/endotoxin translocation and its clinical relevance remains
controversial, many lines of evidence support the concept that the gut may be the
reservoir for systemic sepsis and subsequent MOF in a number of pathophysiologic
states.
PMID- 9657253
TI - The role of histamine in platelet aggregation by physiological and immunological
stimuli.
AB - BACKGROUND: Platelets participate in allergic and inflammatory processes beside
their role in haemostasis and thrombosis. This paper reports the level, the
uptake, the metabolism and the release of histamine in human platelets. The
effects of exogenous histamine, as well as the receptor and signal transduction
of these effects, are also described. METHODS: Purified suspensions of platelets,
prepared from healthy volunteers and from atopic patients, were exposed in vitro
to physiological and immunological stimuli. Platelet aggregation was measured by
the increase in light transmission; histamine content and release, as well as
cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet
histamine forming capacity, and the uptake of exogenous histamine, were measured
with a radioisotopic method. RESULTS: Human platelets contain 72.5 +/- 9.6pmoles
of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/-
3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine
(10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human
platelets take up the preformed amine by a calcium and energy-dependent process,
and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist,
and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of
intracellular histamine receptors. Histamine is also metabolized by human
platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a
progressive aggregation, associated with histamine release. The same is observed
in platelets isolated from atopic patients exposed to anti-IgE antibodies.
Exogenous histamine dose-dependently potentiates the aggregation induced by
physiological and immunological stimuli. In resting platelets cytosolic calcium
level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by
anti-IgE; this effect is potentiated by 10(-5) M histamine. CONCLUSIONS: The
synergistic effect between histamine and other monoamines on platelet aggregation
may explain some aspects of allergic vasculitis in which platelet aggregation is
present.
PMID- 9657254
TI - Regulation of interleukin-6, and macrophage colony-stimulating factor mRNA levels
by histamine in stromal cell line (MC3T3-G2/PA6).
AB - OBJECTIVE: The aim of this study was to examine the role of histamine in
regulation of IL-6 and M-CSF gene expression in bone marrow stromal cells. Total
cellular synthesis was also estimated for IL-6. MATERIALS: The effects of the
amine were evaluated using the stromal cell line, MC3T3-G2/PA6 (PA6). RESULTS:
Histamine caused a distinct accumulation of IL-6 mRNA in the cells, whereas it
decreased M-CSF transcripts. Both pyridylethylamine, a H1 agonist, and dimaprit,
a H2 agonist, caused a large increase in the level of IL-6 mRNA in PA6 cells. The
histamine-induced expression of IL-6 mRNA was associated with enhanced secretion
of IL-6, as determined by ELISA. CONCLUSIONS: These results, together with the
results of our previous studies, suggest that histamine produced by stromal
macrophages differentially regulates the production of IL-6 and M-CSF in other
kinds of stromal cells and hence promotes differentiation and/or proliferation of
hematopoietic progenitor cells.
PMID- 9657255
TI - Effects of the cyclooxygenase-2 inhibitor NS-398 on thromboxane and leukotriene
synthesis in rat peritoneal cells.
AB - OBJECTIVE: Inhibition of inducible cyclooxygenase (COX)-2 has been suggested to
offer therapeutic advantages without some side effects associated with the
inhibition of constitutive COX activity. These side effects encompass asthmatic
responses that can be induced by analgesic/ antiphlogistic drugs and are possibly
related to increased leukotriene (LT) biosynthesis. We have therefore
investigated whether or not the selective COX-2 inhibitor NS-398, similar to
indomethacin, stimulates leukotriene (LT) biosynthesis in rat peritoneal cells.
METHODS: Three hours after rats had received intraperitoneal injections of
bacterial lipopolysaccharide (LPS) or saline, cells were obtained by peritoneal
lavage. Northern blot analysis confirmed induction of COX-2 mRNA by LPS
treatment. For determination of eicosanoid biosynthesis, peritoneal cells were
incubated in the presence of various concentrations of test compounds for 60 min.
The supernatants were used for radioimmunological determination of immunoreactive
eicosanoids. RESULTS: In cells from LPS treated rats, but not in controls, NS-398
(10-300nM) reduced the amount of TXB2-like immunoreactivity (IR) in the
supernatants, the maximum effect being a 25% inhibition. At these concentrations,
there was no detectable effect of NS-398 on the amount of LTB4-IR or LTC4-IR in
the supernatants. At higher concentrations (1-10 microM), NS-398 caused further
inhibition of TXB2 synthesis, an effect that was observed also in non-LPS treated
preparations. A significant increase of LTB4-IR was caused by 3-10 microM NS-398.
Indomethacin (3-100 nM) reduced the amount of TXB2-IR, and at >10 nM increased
the amount of LTB4- and LTC4-IR in the supernatant. CONCLUSIONS: The results show
that concentrations of NS-398 that selectively inhibited COX-2 activity, produced
no detectable increase in LT biosynthesis, thus raising the possibility that COX
2 inhibitors are less likely than non-selective COX inhibitors to produce LT-
related side effects.
PMID- 9657256
TI - Bradykinin increases intracellular calcium levels in a human bronchial epithelial
cell line via the B2 receptor subtype.
AB - OBJECTIVE: To determine which types of kinin receptor are present in human
bronchial epithelial cells we studied the capability of bradykinin to mobilize
intracellular Ca2+ ([Ca2+]i) in a human bronchial epithelial cell line (16HBE
cells). MATERIAL: Human bronchial epithelial cell line transformed with an
original defective simian virus 40 (SV40). TREATMENT: Bradykinin (0.1 pM to 0.1
microM), des-Arg9 bradykinin (1 microM), des-Arg10) kallidin (1 microM),
indomethacin (1 microM), phosphoramidon (1 microM), captopril (1 microM), des
Arg9-[Leu8]bradykinin (1 microM), HOE 140 (DArg-[Hyp3, Thi5, DTic , Oic8]
bradykinin) (1 microM), and NPC 16731 (DArg-[Hyp3, Thi5, DTic7, Tic8]-bradykinin)
(1 microM). METHODS: The mobilization of [Ca2+]i was determined by the fura-2
method. Two sample Wilcoxon rank-sum (Mann-Whitney) test was used for statistical
calculations. RESULTS: Bradykinin, but not the selective agonists for kinin B1
receptor des-Arg9 bradykinin and des-Arg10 kallidin, increased the mobilization
of [Ca2+]i (EC50, 0.079+/-0.009nM) in 16HBE cells in a concentration-dependent
manner. Pretreatment with the cyclooxygenase inhibitor indomethacin (1 microM) or
the peptidase inhibitors, phosphoramidon (1 microM) or captopril (1 microM), did
not affect the response to bradykinin. The kinin B1 receptor antagonist, des-Arg9
[Leu8]bradykinin (1 microM), was inactive. HOE 140 and NPC 16731, two selective
antagonists of the kinin B2 receptor abolished the response to bradykinin (IC50
of HOE 140 and NPC 16731 were 0.52+/-0.037nM and 1.67 +/- 0.41 nM, respectively).
CONCLUSIONS: The present data indicate the presence of kinin B2 receptors in the
16HBE cells.
PMID- 9657257
TI - Surrogate thrombopoietin.
AB - The extracellular domain of human c-Mpl, the receptor for thrombopoietin (TPO),
was expressed as a chimeric protein with the interleukin-2 receptor alpha chain
on the surface of murine B cell-line B300-19. BALB/c mice were immunized with
cells expressing the chimeric protein. The IgG purified from the resulting immune
serum immunoprecipitated human c-Mpl. The immune IgG supported proliferation of
both stable transfectant Ba/F3 cells expressing whole c-Mpl molecules (c-Mpl
Ba/F3 No. 9) and UT7/TPO cells bearing naturally occurring c-Mpl, whereas it did
not support the growth of the untransfected parental Ba/F3 cells. Cell growth was
induced using 3 to 100 microg/ml of immune IgG in a dose-dependent manner, but
this induction was decreased at doses higher than 100 microg/ml. Non-immune IgG
did not affect cell growth of c-Mpl-Ba/F3 No. 9 cells. Although the Fab fragment
of immune IgG also immunoprecipitated c-Mpl, it did not support cell growth at
concentrations as high as 180 microg/ml, implying that the bivalent binding of
receptors by antibodies is essential for cell proliferation. These results
suggest that antibodies against human c-Mpl stimulate the proliferation and
differentiation of megakaryocytes by their bivalent binding to receptors like
TPO.
PMID- 9657258
TI - Effect of Pseudomonas aeruginosa exotoxin A on CD3-induced human T-cell
activation.
AB - The effect of Pseudomonas aeruginosa (PA) exotoxin A (P-ExA) on CD3-induced T
cell activation was studied on the level of T-cells (proliferation, synthesis of
interleukin (IL)-2, expression of IL-2R complex, ICAM-1,2 and LFA-1 molecules),
and on the level of monocytes (expression of ICAM-1,2, LFA-1 molecules, as well
as FcRI and CD14 receptors). We found that: (1) P-ExA blocked T-cell
proliferation and this effect was totally reversed by intact monocytes, and
partially by IL-2 or TPA but not by costimulatory cytokines (IL-1alpha, IL-1beta,
TNF-alpha or IL-6); (2) P-ExA transiently, in short-term cultures (48 h),
inhibited synthesis of IL-2; (3) prolonged stimulation (96 h) of peripheral blood
mononuclear cells (PBMC) or CD4 + T-cells with P-ExA in high or low doses (100
and 10 ng/ml, respectively), enhanced the level of IL-2 in the cultures; (4) P
ExA at low dose, combined with IL-1beta, TNF-alpha or IL-6, up-regulated
synthesis of IL-2; and (5) stimulation of T-cells with anti-CD3 monoclonal
antibody (mAb) and P-ExA at high dose diminished the expression of the p55 chain
but not of the p75 chain of IL-2R complex and slightly affected the expression of
CD3 complex, ICAM-1,2 and LFA-1 molecules. Hence, P-ExA can regulate the level of
IL-2 in cultures of CD3-induced T-cells either by inhibition of IL-2 consumption
(when P-ExA is applied in high dose), or by induction of IL-2 production (a
costimulatory effect exerted by P-ExA in low dose in combination with monokines).
Action of P-ExA on monocytes resulted in: (1) inhibition of the expression of
ICAM-1,2 molecules and their ligand LFA-1 molecule; (2) low expression of FcRI
receptor (a ligand for Fc part of CD3 mAb); and (3) inhibition (over 90%) of the
expression of CD14 molecule. In conclusion, P-ExA-induced anergy of T-cells
depends on: (a) decrease in the affinity of IL-2R complex on activated T-cells;
and (b) inhibition of the accessory activities of monocytes.
PMID- 9657259
TI - Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic
cardiomyopathy.
AB - Cardiotrophin-1 (CT-1), a cytokine with structural similarities to interleukin-6,
has been shown to signal through gp130-dependent pathways. In vitro, CT-1
promotes the survival and induces hypertrophy of neonatal cardiomyocytes. Since
acute Chagas' disease involves an inflammatory response followed by chamber
dilation, with subsequent compensatory hypertrophy, we hypothesized CT-1 and
gp130 may participate in this disease process. Thus, we investigated expression
and localization of these moieties during acute Chagasic cardiomyopathy. Lewis
rats (n = 6/group) were either inoculated with cell culture-derived T. cruzi
trypomastigotes or saline, and sacrificed 15 days later. Hearts were collected
for histology, immunohistochemistry (IHC), mRNA, and protein analyses. Histology
showed dense myocardial infection with amastigotes and diffuse mononuclear cell
infiltrate. Northern blot analysis showed low level expression of CT-1 mRNA in
controls, which was markedly elevated in infected animals (2.5-fold; P < 0.001).
Similarly, Western blotting showed a twofold elevation of CT-1 protein in
infected animals (P < 0.025). Likewise, levels of both gp130 mRNA and protein
were low in controls, but were approximately threefold higher in infected
animals. IHC showed weak and diffuse staining for CT-1 in control myocardium,
while intense staining especially localized to the cytoplasmic region of
cardiomyocytes, was found in infected animals. Although gp130 immunoreactivity
was observed in both normal and infected myocardium, more intense staining was
found in infected animals. Unlike CT-1, gp130 staining was granular, and was
present in both the cytoplasm as well as in the perinuclear region. These data
suggest that there is substantial overexpression of both CT-1 and gp130 in the
heart during acute Chagasic carditis. Their overexpression may provide a
mechanism for myocyte protection, and for development of compensatory cardiac
hypertrophy following myocardial damage in this form of cardiomyopathy.
PMID- 9657260
TI - MHC class II/T-cell receptor interactions potentiate secretion of IgG but not IgM
in response to T-dependent antigens.
AB - We have examined whether the interaction of peptide-loaded MHC molecules on the
surface of B-cells with antigen-specific T-cell receptors (TCRs) enhances Ig
secretion in the presence of other antigen-independent interactions in vitro. B
cells specific for region 25-40 of beta-lactoglobulin (beta-LG) were stimulated
in a T-cell dependent manner using plasma membranes (PM) derived from two
different T-helper (Th) clones, culture supernatants of activated Th2 cells and
beta-LG as a specific antigen. PM were obtained from either the beta-LG-specific
T-cell clone H1.1 which can mediate specific TCR/MHC class II interactions as
well as antigen-independent ones or from the D10 clone which bears a TCR of an
irrelevant specificity and thus, can only mediate antigen-independent
interactions. IgG, but not IgM, secretion was specifically enhanced by H1.1 PM,
but not D10 PM in the presence of beta-LG. Furthermore, a blockade of TCR/MHC
class II interactions using either anti-T-cell receptor, beta or anti-CD4
monoclonal antibodies inhibited this enhanced IgG secretion in response to beta
LG. The results show that while antigen-independent interactions between T- and B
cells can enhance secretion of IgM antibodies, specific interactions between TCRs
and peptide:MHC complexes stimulate B-cells to enhance secretion of IgG but not
IgM antibodies. This mechanism may contribute to antibody secretion only from B
cells activated through cognate interaction in vivo.
PMID- 9657261
TI - Roles of protein phosphatase 2A in IL-6 signal transduction in Hep3B cells.
AB - IL-6 is a pleiotropic cytokine that modulates the diverse functions of
hepatocytes such as acute phase responses and inflammation. When human hepatoma
cells, Hep3B cells, were treated with IL-6, p140 was phosphorylated rapidly and
reached its maximal rate at 1 min after treatment. Okadaic acid, an inhibitor of
protein phosphatase 1 and 2A, affected IL-6-induced p140 phosphorylation.
Interferon regulatory factor-1 (IRF-1) is a transcription factor on the enhancer
of type I interferons, and its gene expression is induced by IL-6. When IRF-1
promoter-luciferase construct was transfected into Hep3B cells, okadaic acid
increased IL-6- induced IRF-1 promoter activity. In addition, co-transfection of
protein phosphatase 2A (PP2A) antisense constructs further increased IL-6-induced
IRF-1 promoter activity, suggesting that PP2A is involved in IL-6 signaling. In
addition, IL-6 directly induced the PP2A phosphorylation. PP2A phosphorylation
was maximal at 1 min after IL-6 stimulation, but it was not induced by other
inflammatory cytokines such as TNF-alpha or TGF-beta. Furthermore, IL-6 activated
PP2A activity simultaneously. Taken together, these data indicate that IL-6
modulates the functions of PP2A which is involved in downstream events of IL-6
signaling in Hep3B.
PMID- 9657262
TI - LAG-3 does not define a specific mode of natural killing in human.
AB - LAG-3 is a gene localized on the band p13 of human chromosome 12, close to the NK
gene complex (NKC), expressed on activated NK cells and encoding a receptor for
MHC class II molecules. Recently, LAG-3 has been proposed to define a specific
mode of natural killing in mice. The putative role of LAG-3 on human natural
killer cytotoxicity has been examined with specific monoclonal antibodies and a
recombinant soluble form of LAG-3. Neither the antibodies, which are able to
block the interaction with the ligand, nor the recombinant product, which has
retained its binding capacity for MHC class II, had an effect on the natural
killing of various target cells. Furthermore, in redirected killing assays, none
of these antibodies were able to modulate either positively or negatively the
cytotoxicity. Taken together, these data show that LAG-3 has no transducing
activity involved in NK cytotoxicity, ruling out the existence of a specific mode
of natural killing defined by this molecule in humans.
PMID- 9657263
TI - Humoral immune response to a 200-kDa glycoprotein antigen of Saccharomyces
cerevisiae is common in man.
AB - According to Heelan et al. patients suffering from Crohn's disease (CD) produce
antibodies against a cell wall associated glycoprotein antigen gp200 of the yeast
Saccharomyces cerevisiae, while healthy people do not. Here the authors show,
that antibodies against this glycoprotein gp200 can also be detected in the sera
of healthy humans. The intensity of the antibody titer which is measured by
immunoblot experiments is independent from the state of health. The Saccharomyces
cerevisiae specific gp200 is a highly glycosylated protein localized not only in
the cell wall but also accumulated in the culture medium. Some of the tested sera
from CD patients, as well as from healthy adults, also reacted with a 120-kDa
glycoprotein which is to be found in preparations containing secreted proteins.
Because the binding of antibodies is greatly reduced by periodate treatment of
gp200 and by the 120-kDa polypeptide, it is very likely that their carbohydrate
moieties are the antigenic determinants against which the specific human
antibodies are directed. The human humoral immune response applies only to
Saccharomyces cerevisiae antigens, because no analogous immune responses could be
detected against antigens derived from the yeast Arxula adeninivorans.
PMID- 9657264
TI - Anti-Lewis X antibody and Lewis X-anti-Lewis X immune complexes in Helicobacter
pylori infection.
AB - A molecular similarity of Lewis antigens expressed by Helicobacter pylori
bacteria and those present in human gastric mucosa has been recognised as a cause
of autoimmunity involved in the pathogenesis of chronic type B gastritis and
gastric and duodenal ulcers. In this study, the expression of Lewis X
determinants was found on 56% of H. pylori strains isolated from patients with
chronic gastritis/gastroduodenitis. Anti-Lewis X IgG as well as Lewis X-anti
Lewis X IgG complexes were detected in the sera from patients and even more
frequently in the sera from healthy blood donors producing antibodies against
surface antigens of H. pylori. It suggested that the initial H. pylori-induced
lesions were independent of anti-Lewis X antibody production. When H. pylori
bacteria expressing Lewis X antigen were treated with anti-Lewis X monoclonal
antibody (mAb) of IgM isotype, they were more susceptible to ingestion by
polymorphonuclear leukocytes (PMN) than untreated bacteria. This fact may lead us
to believe that anti-Lewis X antibody limits the growth of H. pylori on gastric
mucosa.
PMID- 9657265
TI - Accumulation of IL-12-activated antitumor effector cells into lymph nodes of
tumor-bearing mice.
AB - Simultaneous administration of high dose of IL-12 into tumor-inoculated mice
resulted in a marked reduction of tumor growth in parallel with the augmented
generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma
producing Th cells. We found that these IL-12-activated antitumor effector cells
preferentially accumulated in peripheral lymph nodes concomitantly with
lymphadenopathy. However, IL-12 rather induced disappearance of antitumor
effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of
inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing
mice showed a marked IFN-gamma production in response to not only IL-2, IL-12,
anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0
melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL
12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site.
Thus, IL-12 appeared to have a capability of stimulating selective migration of
antitumor cells into lymph nodes and tumor local sites.
PMID- 9657266
TI - Inhibition of B-cell receptor-antigen complex internalization by FcgammaRIIB1
signals.
AB - Membrane-expressed immunoglobulins are B-cell receptors (BCR) for specific
antigens (Ag). Upon Ag engagement of the BCR, B-cells are activated to
internalize Ag-BCR complexes, process Ag and subsequently present Ag-peptides
loaded in class II MHC. Due to the specific nature of the BCR, the cognate
interaction between T-cells expressing Ag-specific T-cell receptor and these Ag
presenting B-cells occur in a highly regulated and precise manner. Accordingly,
efficient control of T-cell activation may be achieved through regulation of Ag
presenting B-cells. A potent form of regulation of lymphocyte responses is
mediated by Ig end-product and anti-idiotypic antibodies via Fc-dependent
mechanisms. In this communication, the authors present data that an anti-idiotype
(anti-Id) Ab inhibits BCR-mediated internalization of specific Ag. Coupling of
BCR to the cytoskeleton was also abortive in anti-Id Ab-treated B-cells.
Inhibition by anti-Id Ab was dependent upon the presence of FcgammaRIIB1 on B
cells. As a result of anti-Id Ab suppression, B-cells were unable to initiate
Ca2+ responses in Ag-specific T-cells. The results suggest that co-crosslinking
of FcgammaRIIB1 and BCR inhibits cytoskeletal coupling and internalization of the
Ag-BCR complex thereby preventing specific Ag presentation by B-cells. Anti-Id Ab
may mediate a negative regulatory mechanism that suppresses B-cell-mediated Ag
specific T-cell activation.
PMID- 9657267
TI - Modulation of NK-target cell interaction by a monoclonal antibody to K562 cells.
AB - In order to identify the target cell recognition molecules involved in the
interaction between natural killer (NK) cells and target cells, we have generated
monoclonal antibodies to K562, NK-sensitive target cells. After screening by
FACScan for the reactivity to K562, one monoclonal antibody (mAb), 4A60, was
selected. MAb 4A60 was found to inhibit the proliferation of NK cells induced by
IL-2 and K562 cells. However, this monoclonal antibody could not significantly
block the conjugate formation between NK and target cells. Moreover, mAb 4A60
only slightly inhibited the cytotoxicity of NK cells induced by IL-2. Protein
analysis showed that mAb 4A60 recognized a 53-kDa protein of K562 cells. Taken
together, these data suggest that mAb 4A60 inhibits the proliferation of NK cells
induced by IL-2 and target cells, and the 53-kDa protein, a tentative ligand of
this mAb of K562, may be involved in this process.
PMID- 9657268
TI - Variable gene segment-specific N-insertions at the signal joint of T-cell
receptor Vbeta-Dbeta recombinations.
AB - The V(D)J recombination of immunoglobulin and a T-cell receptor generates two
species of DNA junctions, a coding joint and a signal joint. Non-templated
nucleotides (N-nucleotides) are inserted in these DNA junctions. We analyzed the
N-insertion at signal joints generated by the Vbeta-Dbeta recombinations. N
insertions were detected at signal joints of Vbeta2, Vbeta3, Vbeta10, Vbeta18 and
Vbeta14 but not in Vbeta8 and Vbeta7. These data show that the N-insertion at
signal joints is dependent on the Vbeta locus used for the recombination. We
suggest that the regional chromosomal configuration may differ in recombinase
accessibility.
PMID- 9657269
TI - Cytofluorometric detection of mitochondrial alterations in early CD95/Fas/APO-1
triggered apoptosis of Jurkat T lymphoma cells. Comparison of seven mitochondrion
specific fluorochromes.
AB - It is commonly accepted that mitochondria undergo major changes early during the
apoptotic process and that these alterations are critical for the death/life
decision. Here we report that Jurkat T cell leukemia cells exhibit a perturbed
incorporation of potential-sensitive fluorochromes. After 6 h of CD95/Fas/APO-1
crosslinking, a significant fraction of still normal-sized Jurkat cells exhibit a
decreased incorporation of three different cationic lipophilic dyes commonly used
for the quantitation of the mitochondrial transmembrane potential (deltapsi(m)):
DiOC6(3), chloromethyl-X-rosamine, and tetramethylrhodaminemethylester. In
contrast, upon induction of apoptosis, cells tend to exhibit an increase in the
fluorescence obtained with rhodamine 123. The increased rhodamine 123
fluorescence into cells undergoing apoptosis is not affected by labeling in the
presence of the protonophore m-chlorophenylhydrazone and thus cannot be
attributed to a change in the deltapsi(m). Six hours after CD95 ligation no
changes are found among normal-sized cells in the incorporation of mitotracker
green and nonylacridine orange, which both measure mitochondrial mass. However, a
fraction of cells exhibit an increased staining with the Apo2.7 antibody which
detects a mitochondrial antigen generated during apoptosis. These findings
underline the importance of using adequate fluorochromes for the quantitation of
mitochondrial changes occurring during early apoptosis. Moreover, they cast
doubts on those studies that, using rhodamine 123, hypothesized that apoptosis
would be associated with a stable or increased deltapsi(m).
PMID- 9657270
TI - Mouse NK1.1+ cytotoxic T cells can be generated by IL-2 exposure from lymphocytes
which express an intermediate level of T cell receptor.
AB - NK-like T cells which express the NK1.1 molecule and CD3 (or TCR) of intermediate
level (CD3int or TCRint cells) were recently demonstrated to be present in
various immune organs, and to have NK-like cytotoxic activity against NK target
cells. In this study, we investigated whether NK1.1- T cells could express NK1.1.
We found that NK1.1+ TCRint cells were much more abundant in the liver (20%) than
in the spleen (2%). When hepatic and splenic mononuclear cells (MNCs) were
cultured either in the absence of IL-2 or in the presence of CD3/TCR cross
linking, the original NK1.1+ TCRint cells disappeared. However, when they were
cultured in the presence of a high dose of IL-2 for 4 days, a new type of NK1.1+
T cell was formed to the extent of approximately 15-20%, and the liver and spleen
contained similar percentages of this new type of NK1.1+ T cells. The phenotypes
of the original and the new type of NK1.1+ T cells were clearly distinct. The
freshly obtained NK1.1+ TCRint cells consisted of double-negative (DN) CD4-CD8-
cells and single-positive (SP) CD4+ cells, whereas the new type of NK1.1+ T cells
predominantly consisted of DN CD4-CD8- cells and SP CD8+ cells and expressed a
high level of CD3 (CD3high or TCRhigh cells). When NK1.1- cells or IL-2 receptor
beta-chain (IL-2Rbeta)- cells were isolated from the liver and spleen, and
cultured in the presence of IL-2 for 4 days, NK1.1+ T cells were generated from
NK1.1- cells, but not from IL-2Rbeta- cells. Our results suggested that the NK1.1
cells, but not IL-2Rbeta- cells, contained the precursor of IL-2-stimulated
NK1.1+ TCRhigh cells. When purified NK1.1- IL-2Rbeta+ TCRint cells were cultured
in the presence of IL-2 for 4 days, approximately 10% of the cells became NK1.1+
TCRhigh cells. Approximately 60% of the purified NK1.1+ TCRint cells lost NK1.1
expression. The IL-2-stimulated NK1.1+ TCRhigh cells that had arisen from NK1.1-
TCRint cells exerted an NK cell-like cytotoxic activity similar to that of the
original NK1.1+ T cells. Thus, NK1.1- TCRint cells could express NK1.1 and exert
NK-like cytotoxic activity regardless of their origin. It appears that NK1.1+
TCRhigh cells can only be induced through an IL-2-stimulation pathway but not via
CD3/TCR cross-linking.
PMID- 9657271
TI - Alkaline phosphatase activity is expressed in murine splenic B-lymphocytes
sensitized in vivo with Tetanus toxoid.
AB - Alkaline phosphatase (APase) activity and proliferative response to Tetanus
toxoid (TT) were measured in murine splenic lymphocytes immunized in vivo with
TT. APase activity was enhanced in TT-stimulated B-lymphocytes concomitant with
an increase in the proliferative response in a dose-dependent manner.
Cytochemical staining for APase using beta-naphthyl phosphate also showed an
increase in APase positive cells in TT-stimulated lymphocyte population. The
results suggest that membrane APase expression is a physiological phenomenon
occurring in antigen-stimulated B-lymphocytes.
PMID- 9657272
TI - Protein kinase C: a potential pathway of macrophage activation with cisplatin.
AB - Cisplatin (CP) has been reported to activate murine macrophages to tumoricidal
state, however, its mechanism of action is not known. In the present study it is
reported that the production of: (a) interleukin-1 (IL-1); (b) tumor necrosis
factor (TNF); (c) nitric oxide (NO); and (d) macrophage-mediated cytotoxicity by
cisplatin-treated bone marrow-derived macrophages were inhibited by PKC
inhibitors H-7 and chelerythrine chloride. Also, it was observed that treatment
of macrophages with CP resulted in the translocation of PKC from the cytosol to
the membrane fraction. These findings suggest the involvement of PKC in the
activation of bone marrow-derived macrophages with cisplatin.
PMID- 9657273
TI - Requirement of the CD8+ or CD4+ T lymphocyte subsets for the rejection of
lymphoma and fibrosarcoma grafts studied in gene knockout hosts.
AB - Rejections of the retrovirus induced lymphomas (ALC and RBL-5) and the
methylcholanthrene (MCA) induced fibrosarcoma (MC57X) grafts were tested in
syngeneic CD8 and CD4 single and double knockout C57BL/6 mice. The results with
the lymphomas showed that the CD8+ T cell deficiency prevented the development of
rejection response induced by immunization. Deficiency of the CD4+ T subset
abrogated also the rejection of ALC. Immunity against the fibrosarcoma cells
developed in both type of single knockout mice, but not in the ones which lacked
both CD4+ and CD8+ T cells. Thus CD8+ T cells were required for rejection of the
lymphoma cells, while the CD4+ T cells only mediated a weak response. In absence
of CD8+ T cells, CD4+ T cells were sufficient to reject the fibrosarcoma cells.
PMID- 9657274
TI - Phospholipid-binding activity of human mannan-binding lectin.
AB - Some C-type lectins possess phospholipid-binding ability, which may be of
physiological importance. Human mannan-binding lectin (MBL) was found to bind
specifically to solid-phase phosphatidylserine (PS), phosphatidylinositol (PI)
and phosphatidylcholine (PC), but not cardiolipin (CL), in a concentration
dependent manner. This property was inhibited by EDTA and by monosaccharides, and
exhibited a similar pH dependence to the carbohydrate (mannan)-binding activity
of MBL. These findings may be of immunological relevance.
PMID- 9657275
TI - Imbalanced distribution of IgM and IgG antibodies against Plasmodium falciparum
antigens and merozoite surface protein-1 (MSP1) in pregnancy.
AB - In malaria endemic areas, pregnancy is assumed to be associated with a specific
reduction in immunity to Plasmodium falciparum malaria. To understand some of the
mechanisms which underlie such a poor immunity, we have attempted to examine the
frequency and distribution of IgM and IgG antibodies to a crude antigenic extract
of parasitized erythrocytes and to the merozoite surface protein-1 (MSP1), in a
population of mothers compared to control non-pregnant women, all living in Dakar
and suburbs. Specifically, this work describes: (i) the responses of mothers and
control women; (ii) the balance between IgM and IgG responses; and (iii)
responses to malarial antigen and to MSP1. An unexpected balance between P.
falciparum-specific IgM and IgG is shown, associated with a substantial increase
in anti-MSP1 IgM, and a decrease in anti-MSP1 IgG in parturients.
PMID- 9657276
TI - Differential induction of immunoglobulin G subclasses by immunization with DNA
vectors containing or lacking a signal sequence.
AB - The route and method used to immunize mice with antigen-expressing DNA plasmids
have an impact on the resulting T-helper cell response and IgG subclass
distribution. Previous findings further indicate that the intracellular targeting
of expressed antigens influences the differentiation of naive T-cells into either
a Th1 or a Th2 type of response. In the present study, we analyzed the levels of
IgG1 and IgG2a antibodies, as correlates of Th2 and Th1 responses, respectively,
after intramuscular injection of mice with plasmids encoding a chimeric protein
containing a Plasmodium falciparum blood stage antigen expressed in two different
forms. One plasmid expresses the antigen in a secreted form as it is preceded by
a signal sequence while expression from the other plasmid, lacking this sequence,
results in cytoplasmic localization of the antigen. Mice immunized with the
plasmid encoding secreted antigen responded with predominantly IgG1 antibodies.
In contrast, sera from mice immunized with the plasmid expressing cytosolic
protein displayed a mixed IgG1/IgG2a profile. In line with previous findings, our
results suggest that the intracellular targeting of proteins expressed by DNA
plasmids is an important factor for the differentiation of Th cells and the
resulting subclass pattern of IgG responses.
PMID- 9657277
TI - Frequency of the delta ccr5 deletion allele in the urban Brazilian population.
AB - Studies on screening genes conferring resistance to HIV-1 and AIDS onset have
shown a direct relationship between a 32 base pair (bp) deletion in the CCR5 beta
chemokine receptor gene (delta ccr5 mutant allele) and long survival of HIV-1
infected individuals bearing this mutation. These findings led to an interest in
studies of delta ccr5 allele distribution in human populations. In the present
study, polymerase chain reactions (PCR) in genomic DNA samples, using specific
CCR5 oligonucleotide primers surrounding the breakpoint deletion, detected a 193
bp product from the normal CCR5 allele and a 161-bp product from the 32-bp
deletion allele. In an investigation of the urban Brazilian population we
detected a 93% frequency of normal CCR5/CCR5 homozygous individuals and a 7%
frequency of CCR5/delta ccr5 heterozygous individuals. The frequency of the delta
ccr5 mutant allele in this population is 0.035; however, no homozygous delta ccr5
individual has been detected thus far. This is the first evidence for the
contribution of the delta ccr5 allele to the genetic background of the urban
Brazilian population, which is characterized by intense ethnic admixture. These
findings open perspectives for further studies on the relationship between delta
ccr5 allele frequency and AIDS onset in high-risk HIV-1 exposures individuals.
PMID- 9657278
TI - The use of dogs as second species in regulatory testing of pesticides. I.
Interspecies comparison.
AB - The relevance of studies in dogs on regulatory testing of pesticides was examined
retrospectively using data of 216 pesticides (acaricides, fungicides, growth
regulators and hormones, herbicides, insecticides, molluscicides, nematicides,
rodenticides, synergists for insecticides) submitted for regulatory purposes
during the past 40 years to the Federal Institute of Health Protection of
Consumers and Veterinary Medicine (BgVV), the competent national authority in
Germany. At first the relevance of the no-observed-effect levels (NOEL) for
safety assessment was evaluated for each chemical in 4-week (subacute), 13-week
(subchronic) and 52/104-week (chronic) toxicity studies carried out on dogs, rats
and mice. After subchronic and chronic application of fungicides the sensitivity
of rats and dogs to the toxic chemicals was quite similar. However, the dog was
generally a more sensitive species to toxic effects of insecticides than rat and
mouse. On the other hand the NOEL was lower in the rat than the dog in chronic
studies on herbicides. When the lowest-observed-effect level (LOEL) was evaluated
in animal species, the dog was the most sensitive in approximately 15% of the
studies. Mice were found to be the most sensitive species only in approximately
1% of the studies on 216 pesticides. Comparison of organ specific toxicity at the
LOEL in subacute studies on fungicides and herbicides revealed a poor correlation
of target-specific organ toxicity across species. However, in the subchronic and
chronic studies (13 and 52/104 weeks) no significant differences in species
specific organ toxicity were observed in the three species rat, mouse and dog.
The only exception were haematoxic effects in chronic studies on herbicides,
which were more frequent in dogs (40%) than in rats and mice (20%). The results
support the established concept that studies on dogs and rats are important for
the safety assessment of pesticides, while studies on mice do not provide further
information, except for detection of an oncogenic potential which is a further
controversial issue. Further analysis of subacute, subchronic and chronic studies
in dogs should reveal if all of the studies are essential for safety assessment
of pesticides.
PMID- 9657279
TI - Application of the queueing theory with Monte Carlo simulation to inhalation
toxicology.
AB - Various models have been developed in modelling of inhalation toxicology. The
deterministic approach, which has been used to date in most of the models, needs
to consider numerous factors, e.g. anatomical structure, breathing frequency,
humidity, metabolism rate, partition coefficients, pulmonary ventilation,
perfusion rates, unidirectional/cyclic air flow, non-steady-state, steady-state,
etc. In the present study, a stochastic approach was used in the modelling of
inhalation toxicology, because there is a phenomenological analogy between the
queueing system and respiratory system dealing with inhaled toxicants. Using the
queueing theory, the amounts of toxicants in the respiratory system, the time
needed to remove the accumulated amounts of toxicants from the respiratory
system, etc. can be estimated. The Monte Carlo simulation of queueing process was
performed to analyse cigarette smoking, and shows the potential use of the
queueing theory in inhalation toxicology.
PMID- 9657280
TI - Induction of CYP2A5 by pyrazole and its derivatives in mouse primary hepatocytes.
AB - Mouse liver CYP2A5 is induced by several structurally unrelated compounds. In
intact mouse liver, pyrazole (PYR) and 4-hydroxypyrazole (4-OH) induce
selectively the expression of CYP2A5 while expression of other CYPs is decreased.
In this study we exposed mouse primary hepatocytes to PYR, 4-OH, 4-methylpyrazole
(4Me; 0.1-20 mM) and 4-iodopyrazole (4-I; 0.1-5.0 mM). PYR and its derivatives
increased coumarin 7-hydroxylase activity, with 4-1 and 4-OH being the strongest
inducers, by 114-fold and 41-fold, respectively. However, only 4-1 treatment
increased markedly the CYP2A5 protein content. CYP2B9/10-mediated
pentoxyresorufin O-deethylase activity (PROD) was decreased by 80% by 4-Me and 4
1, and by 50% by 4-OH while PYR had no marked effect. PYR and 4-Me increased 2-
to 3-fold the CYPA1/2-mediated ethoxyresorufin O-deethylase activity (EROD) while
4-OH and 4-1 had no marked effect on this enzyme. The time of exposure markedly
affected the inducibility of 4-OH such that induction was 7-fold stronger when it
was added to the incubation medium 24 h after the isolation of hepatocytes
compared to exposure 3 h after their isolation. Cimetidine prevented the
induction of coumarin 7-hydroxylase activity by PYR and 4-OH by 46 and 74%,
respectively indicating that their effects on the expression of CYP2A5 are, at
least partly, mediated via their metabolites. The data demonstrate that the
regulation of CYP2A5 is different from other monooxygenases and that the effects
of pyrazole and its derivatives are different in vivo and in vitro. Also, the
timing of exposure markedly affects the inducibility of 4-OH in hepatocytes.
PMID- 9657281
TI - Mutagenic properties of 1,2,3,4-tetrahydronaphthaline-1-hydroperoxide, a model
compound for organic peroxides in Diesel exhaust.
AB - The genotoxicity of the organic peroxide 1,2,3,4-tetrahydronaphthaline-1
hydroperoxide (or tetraline-1-hydroperoxide, THP) was investigated in the Ames
assay without a metabolic activating system using Salmonella typhimurium strains
TA 98, TA 100, and TA 102. THP served as a model compound for higher organic
peroxides, which can arise from autoxidation of hydrocarbons, e.g. in Diesel
exhaust. While THP induced no mutagenic response in S. typhimurium TA 98, it was
directly mutagenic in strains TA 100 and TA 102. These data, along with findings
on mutagenic properties of other alkyl hydroperoxides, suggest that such
compounds deserve further investigation regarding their genotoxic potential and
occurrence in the environment.
PMID- 9657282
TI - The nephrotoxicity and hepatotoxicity of 1,1,2,2-tetrafluoroethyl-L-cysteine in
the rat.
AB - Recent studies have shown that tetrafluoroethylene is a renal and hepatic
carcinogen in the rat. In this study, we have examined the ability of a single
i.p. dose of 1,1,2,2-tetrafluoroethyl-L-cysteine (TFEC), a major metabolite of
tetrafluoroethylene, to produce hepatic and renal injury in male and female rats.
We have also examined the effect of blocking the renal organic anion transport
system with probenecid and of inhibiting the activity of cysteine conjugate beta
lyase with aminooxyacetic acid on the extent of renal injury produced by TFEC.
Doses of > or = 12.5 mg/kg TFEC produced renal tubular necrosis to the pars recta
of the proximal tubules within 24 h in both male and female rats. This was
associated with an increased kidney to body weight ratio and plasma urea at doses
of > or = 25 mg/kg. No consistent evidence of liver injury was seen at doses up
to 50 mg/kg TFEC in rats of either sex, although occasional vacuolation of
hepatocytes and a small dose-related increase in liver to body weight ratio was
observed. Prior treatment of female rats with probenecid completely prevented the
renal injury produced by either 25 or 50 mg/kg TFEC as judged by plasma urea and
histopathology. However, prior treatment of female rats with aminooxyacetic acid
afforded no protection against the nephrotoxicity produced by either TFEC or the
cysteine conjugate of hexachloro-1,3-butadiene. Thus no major sex difference in
nephrotoxicity in the rat was seen with TFEC, while accumulation of TFEC, or its
N-acetyl derived metabolite, into renal proximal tubular cells via a probenecid
sensitive transport system appears to be a key event in the mechanism of
nephrotoxicity. The lack of protection observed with the cysteine conjugate beta
lyase inhibitor, aminooxyacetic acid, may reflect the inability to completely
inhibit the mitochondrial form of this enzyme and thereby prevent the formation
of the reactive metabolite. Our acute studies provide no insight concerning the
liver carcinogenicity of tetrafluoroethylene.
PMID- 9657283
TI - Stimulation of liver heme oxygenase in hexachlorobenzene-induced hepatic
porphyria.
AB - We have measured liver heme oxygenase, a heat shock protein known to be increased
under conditions of oxidative stress, to obtain additional evidence for an
oxidative stress mechanism in hepatic uroporphyria induced by hexachlorobenzene
(HCB). We have studied heme oxygenase at different times during HCB treatment and
in two strains of rats (Agus and Wistar strains), which are known to differ in
their sensitivity to the porphyria-inducing properties of HCB, in order to
ascertain whether the same time course and genetic differences known to exist for
the induction of porphyria also apply to hepatic oxidative stress. HCB induced
heme oxygenase and accumulation of porphyrins in the liver of rats of both
strains; no significant difference was found between the two strains in the HCB
induced heme oxygenase activity. The increased activity of the enzyme was first
detected during the early phases of treatment, when a modest increase in liver
porphyrins was observed; heme oxygenase remained at induced levels for several
weeks during HCB treatment, and was still raised when an increase in total liver
iron content and the onset of marked porphyria were also found. In contrast to
the effects of HCB, phenobarbitone sodium (given in the drinking water for up to
4 weeks) produced similar elevations of total liver cytochrome P450 as HCB, but
did not stimulate heme oxygenase or increase the total liver content of either
iron or porphyrins. These results are compatible with an oxidative stress
mechanism in HCB-induced liver toxicity and porphyria, but also suggest the
existence of successive stages in the induction of hepatic porphyria, with more
than one mechanism contributing to the marked accumulation of uroporphyrin.
PMID- 9657284
TI - Elucidation of mitochondrial effects by tetrahydroaminoacridine (tacrine) in rat,
dog, monkey and human hepatic parenchymal cells.
AB - Tetrahydroaminoacridine (tacrine) causes morphological and functional changes in
the endoplasmic reticulum, ribosomes, and mitochondria in the liver of humans and
animals. In order to investigate species differences as well as to understand the
morphological changes, we examined the effects of tacrine on respiration and
electron transport in mitochondria isolated from rat, dog, monkey, and human
liver. Tacrine produced significantly decreased respiratory control ratios (RCR)
in all species at concentrations ranging from 5 to 25 microg/ml. Human
mitochondria were more sensitive to tacrine effects with RCR decreased 24% at 5
microg/ml while other species were unaffected at this concentration. The tacrine
effects were characterized by increased hepatic mitochondrial State 4 respiration
in rats and decreased State 3 respiration in humans. Mitochondria from aged rats
were more sensitive to the effects of tacrine than mitochondria from young
animals, with significantly decreased RCR at 10 microg/ml in aged rats while
mitochondria from young rats were unaffected at this concentration. Concomitant
with the respiratory changes, mitochondrial DNA synthesis was impaired. Since
tacrine undergoes extensive biotransformation, we also explored the possibility
that metabolites could exert detrimental effects. The ranking order of potency
for decreasing RCR caused by monohydroxylated metabolites was: tacrine > 4-OH and
7-OH > 2-OH, 1-OH, and velnacrine with the latter group of metabolites having no
effect on mitochondrial respiration at concentrations up to 50 microg/ml. In vivo
administration of 20 mg/kg tacrine to rats for up to 20 days caused a paradoxical
increase in RCR and P/O on Day 1 and decreased RCR on Days 9 and 20, the later
findings being consistent with in vitro data. From these data we propose that
tacrine does not necessarily have to be metabolized to exert effects on
mitochondria at different sites in the electron transport chain that differ among
species. These effects are exacerbated in mitochondria from older animals and
humans appear to be more sensitive than the laboratory animals studied.
PMID- 9657285
TI - Evaluation of toxicity indicators in rat primary astrocytes, C6 glioma and human
1321N1 astrocytoma cells: can gliotoxicity be distinguished from cytotoxicity?
AB - A comparison was made of rat primary astrocytes, C6 glioma cells pre-treated with
dibutyryl cyclic AMP, and the human astrocyte 132N1 cell line using a range of 40
compounds and the neutral red (NR) assay. The 40 chemicals included substances
known to be toxic to astrocytes or neurons, to be generally cytotoxic or not
thought to be toxic to nervous tissue. For those compounds which were toxic,
changes in glial fibrillary acidic protein (GFAP) levels were measured in the
primary and C6 cultures, and changes in vimentin and S-100 measured in the C6
cells. The number of compounds with EC50 values < 2000 microg/ml for the NR assay
for the different cell cultures were as follows: primary astrocytes, 19; C6
cells, 15; and 1321N1 cells, 11. The log of the EC50 values for the NR assay for
the test compounds between the three cell types was not significantly different
at the 5% level by paired Student's t-test. For the toxic substances the
correlation coefficients of the EC50 values between primary cells and the C6 or
1321N1 cells were r > 0.5, and between the C6 and 1321N1 cells r > 0.9. For GFAP
there was a similar degree of correlation in EC50 values between the different
cell types. The GFAP, vimentin and S-100 levels showed similar EC50 values for
the toxicants, but were not as sensitive as the NR assay. The toxic substances
caused altered morphology in the primary, C6 and 1321N1 cells, with increased
branching of cell processes. The combined astrocyte systems identified 8 out of 9
substances reported to be toxic to astrocytes in vivo, together with substances
which have general cytotoxic properties. A number of substances (including the 1
out of 9 reported gliotoxic substances), which may primarily affect neurons,
which may affect nervous tissue after long-term exposure, or which are not
thought to be toxic to nervous tissue, were not detected. The astrocyte systems
positively identify gliotoxic and cytotoxic substances and will allow detailed
mechanistic studies to be made on the different underlying mechanisms.
PMID- 9657286
TI - Effects of vitamin A pretreatment on nickel-induced lipid peroxidation and
concentration of essential metals in liver, kidney and lung of mice.
AB - In the present study we report the effects of pretreatment with large doses of
vitamin A (Vit A, retinol) on hepatic, renal and pulmonary lipid peroxidation,
and Ni and essential metal (Fe, Cu, Zn and Ca) concentrations in mice acutely
exposed to nickel. Vitamin A (250,000 IU/kg per day) was administered by oral
gavage to ICR mice for 7 days. On the 8th day, NiCl2 (5 mg Ni/kg body wt.) was
injected i.p. to Vit A- or vehicle-pretreated mice. Vitamin A pretreatment alone
did not alter lipid peroxidation in liver, kidney and lung. Lipid peroxidation in
liver, kidney and lung was increased after treatment with NiCl2 alone. The extent
of lipid peroxidation levels in Vit A + Ni treated mice was enhanced in liver,
but reduced in kidney and lung. The Ni concentration in these three organs was
below the detection limit (0.09 microg/g) in control and Vit A-pretreated mice.
The accumulation of Ni in Vit A + Ni treated mice was increased in liver, but
decreased in kidney and lung compared to Ni-treated mice. The concentrations of
Fe, Cu, Zn and Ca in these organs were significantly increased in Ni-treated
mice. In Vit A + Ni treated mice, compared to Ni-treated mice, hepatic Fe was
significantly increased while Cu, Zn and Ca levels were reduced, but still higher
than those of control and Vit A-treated mice. In the kidney of Vit A + Ni treated
mice, the increase of Cu, Fe, and Zn but not Ca, was reduced and not
significantly different from control and Vit A-treated mice. Pretreatment with
Vit A reduced the increased Fe, Cu, Zn and Ca concentration in the lung caused by
Ni injection. We therefore conclude that the effect of Vit A pretreatment on Ni
toxicity is organ-dependent.
PMID- 9657287
TI - Albert Einstein and his mentor Max Talmey. The seventh Charles B. Snyder Lecture.
AB - While he was a student at the Munich medical school, Max Talmey strongly
influenced the education of Albert Einstein. Their association occurred during
five years of Einstein's second decade. They lost contact for many years after
each left Munich. Talmey emigrated to the United States and practiced medicine,
mainly ophthalmology, in New York City. He made significant contributions to
medicine, to the popularization of Einstein's work, and to the development of
international languages. The relationship of Talmey and Einstein was rekindled
when Einstein visited and later moved to the United States.
PMID- 9657288
TI - Wooden eyeglass cases.
PMID- 9657289
TI - Changing trends in the etiologic diagnosis of uveitis.
AB - Just as different fads that seize the imagination of the general public are often
carried to excess, so diagnostic or therapeutic fads may take over in the
practice of medicine. Analysis of 33 surveys of the causes of uveitis reported by
ophthalmologists over the course of 120 years shows how some diagnoses such as
syphilis and tuberculosis fell from favor because tests ruled out these diseases,
whereas others such as toxoplasmosis became popular because of the finding of the
organism in a few cases by a famous ophthalmic pathologist. Yet others (pars
planitis, sarcoidosis) were not even causes of disease, but rather merely
descriptive, or the ocular component of a systemic disease whose etiology and
pathogenesis remain unknown. We will examine the waxing and waning of these
diagnostic categories and the impressive confidence of some clinicians in their
own diagnostic acumen as they made diagnoses often unsupported by objective
evidence.
PMID- 9657290
TI - Stephen Girard (1750-1831): a one-eyed American patriot.
AB - Stephen Girard trader, banker, millionaire, and patriot lived 81 full and
exciting years. Apparently born with a blind or amblyopic right eye, he emigrated
from Bordeaux, France, via Santa Domingo to the United States, and finally
settled in Philadelphia, where he developed a successful maritime trade.
Ultimately, Girard became the first multimillionaire in the United States.
Extremely generous, he often walked from his home in the center of Philadelphia
to his farm in what is now South Philadelphia distributing shoes to needy
children. Probably Girard's most heroic gestures were his gallant fight against
the yellow fever epidemic in 1793 and his loan to the U.S. government during the
War of 1812, which allowed the bankrupt country to continue the conflict and
ultimately to win the war.
PMID- 9657291
TI - Notes on Voltaire's 'The elements of Sir Isaac Newton's Philosophy'.
PMID- 9657292
TI - Little known aspects of Jules Gonin's life.
PMID- 9657293
TI - The history of the evil eye and its influence on ophthalmology, medicine and
social customs.
AB - Belief in the evil eye is one of the oldest and most widespread superstitions in
the world. The concept of the evil eye has influenced present day ophthalmology,
medicine, and social customs. Oculus sinister (OS), the serpent and the staff of
Asclepius, the symbol of RX, and many social customs are historically related to
the evil eye.
PMID- 9657295
TI - The great mind of Thomas Young (1773-1829).
PMID- 9657294
TI - The Origin of Species, Man's Place in Nature and the naming of the calcarine
sulcus.
AB - In The Origin of Species by Means of Natural Selection of 1859, Charles Darwin
provided a detailed, coherent proposal: species changed into new ones by the
action over time of natural forces in the environment acting continuously on the
variations always present within species. Readers immediately extrapolated
Darwin's argument concerning lower animals to the implications for humans, and
its denial of a special creation of humans. In opposition to Darwin's theory,
Britain's preeminent paleontologist and comparative anatomist, Richard Owen,
argued that man was unique among all creation in the possession of a particular
structure within the brain, the 'Hippocampus minor'. Darwin's great defender,
Thomas Huxley, demonstrated that this structure also existed in monkeys and apes,
and that it was simply a manifestation of a 'particular sulcus' in the posterior
cerebral cortex, which he named as the 'calcarine' sulcus. The home of the visual
striate cortex was thus named as part of the controversy surrounding the birth of
evolutionary theory, soon to be accepted as the great unifying concept in all of
biology.
PMID- 9657296
TI - Ophthalmic injuries and civil war medicine.
PMID- 9657297
TI - Evolution of the British ophthalmoscope.
PMID- 9657298
TI - Unknown ancient Greek ophthalmological instruments and equipment.
AB - Discoveries of some ancient medical instruments and equipment found in the
Hellenic world have been published in magazines of general interest and in a rare
Greek medical journal, yet none caught the attention of ophthalmologists. Among
these instruments are two forms of the famous 'Kenteterion', dating from the
Hellenistic period, used for the couching of cataract. These were found on the
island of Milos in the last century. Two magnifying lenses of the Archaic period
from the recent Cretan excavations gave us the opportunity to discuss the problem
of their medical use. The two drop-bottles from the excavations on Cyprus and at
Tanagra, which are also described, seem to be of medical, and possible
ophthalmological, use.
PMID- 9657299
TI - C.S. O'Brien: founder of the Department of Ophthalmology, the University of Iowa.
AB - Cecil Starling O'Brien, M.D. (1889-1977), was the founder (1927) of the
Department of Ophthalmology at the University of Iowa, and he is credited with
the establishment of a strong department that has made many important
contributions to ophthalmology. The surviving O'Brien residents were interviewed
on videotape, and this article is a composite of their memories together with a
brief biographical sketch of Dr. O'Brien.
PMID- 9657300
TI - Cornelius Rea Agnew, M.D., and the code of ethics of the Medical Society of the
State of New York.
PMID- 9657301
TI - The effect of forskolin on the sound-evoked potentials in the guinea pig cochlea.
AB - The effect of forskolin (FSK) on cochlear sound-evoked potentials was examined in
the guinea pig. The perfusion of the scala vestibuli (SV) with FSK (2 x 10(-4) M)
produced a significant increase in the amplitude of negative summating potential
(- SP) with no change in cochlear microphonics (CM) amplitude, and a significant
decrease in the amplitude of compound action potential (CAP) with a significant
prolongation of N1 latency and a 20 dB CAP threshold elevation. The results lead
us to speculate that FSK-induced changes may be involved in the transient
formation of endolymphatic hydrops.
PMID- 9657302
TI - Failure of forskolin to elevate the endocochlear potential in experimental
endolymphatic hydrops of the guinea pig.
AB - The effect of forskolin (FSK) on the endocochlear potential (EP) in scala media
(SM) was examined in experimental endolymphatic hydrops of the guinea pig. Two
weeks after obliteration of the endolymphatic sac the EP of hydroptic ears and
that of the contralateral control ears were measured by means of microelectrodes.
The perfusion of scala vestibuli (SV) with FSK (200 microM) produced EP elevation
in the contralateral control ears but failed to do so in the experimental
hydroptic ears. Histological examination of experimental endolymphatic hydrops
showed mild hydrops with intact appearance of outer and inner hair cells, and the
stria vascularis. The mechanism underlying the failure of FSK to elevate the EP
in experimental endolymphatic hydrops is discussed.
PMID- 9657303
TI - Effect of acetazolamide on cation concentration in the endolymph of the
endolymphatic sac.
AB - Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been reported to
decrease the endolymphatic sac (ES) DC potential (ESP) in the guinea pig. To
assess the involvement of cation transport in the ESP change by ACTZ we examined
the effect of ACTZ upon the K+ and Na+ activities of the ES endolymph in the
guinea pig using ion-sensitive microelectrode. ACTZ (10 mg/kg), a dose that
produces the ESP maximum reduction, produced a significant increase in Na+
activity of the ES endolymph with no change in K+ activity. The results suggest
that Na+ transport may be directly or indirectly involved in ESP reduction by
ACTZ, and that a Na(+)-H+ exchanger may be involved in Na+ influx pathway from
endolymph to the ES epithelial cells.
PMID- 9657304
TI - Effect of intravenous vasopressin on endocochlear potential and systemic blood
pressure in the guinea pig.
AB - The effects of intravenous arginine-vasopressin (AVP) on the endocochlear
potential (EP) and systemic blood pressure (BP) were examined in the guinea pig.
Intravenous AVP (10(-7) M) elevated BP significantly but did not change EP. AVP
(10(-8) M) produced a significant decrease in the amplitude of EP but did not
change mean blood pressure significantly. AVP at 10(-9) M did not affect EP or
BP. These results suggest that intravenous AVP might have an inhibitory effect on
EP.
PMID- 9657305
TI - Selective expression of mercurial-insensitive water channel (AQP-4) gene in
Hensen and Claudius cells in the rat cochlea.
AB - We investigated the cellular localization of mercurial-insensitive water channel
(MIWC) mRNA in the rat cochlea. MIWC gene expression was detected in the
supporting cells in Corti's organ. The function of these supporting cells is not
clear, but the results suggest that they reabsorb water and play a role in
maintaining the ionic balance of inner ear fluids.
PMID- 9657306
TI - The neurosteroid pregnenolone sulfate excites medial vestibular nucleus neurons.
AB - To examine the relationship between neurosteroids and vertigo we performed
electrophysiological studies to determine whether pregnenolone sulfate (PS)
affects the activity of medial vestibular nucleus (MVN) neurons in alpha
chloralose-anesthetized cats. Single neuronal activities in the MVN were recorded
extracellularly using a glass-insulated silver wire microelectrode attached along
a seven-barreled micropipette. 3 mM PS, 1 M glutamate and 3 mM NaCl were applied
microiontophoretically in the immediate vicinity of the target neurons. The
effects of these drugs were then examined on type I and type II neurons,
identified by their responses to horizontal and sinusoidal rotations. The
iontophoretic application of PS dose-dependently increased the spontaneous firing
of both type I and type II neurons. The larger increase in firing was observed in
type I neurons as compared with type II neurons following the PS application.
These results suggest that PS excites types I and II neurons differentially,
presumably resulting in a disturbance of harmony of the vestibulo-ocular reflex
with ensuing development of vertigo.
PMID- 9657307
TI - Vestibular neuronal function of cats following unilateral vertebral artery
occlusion.
AB - Since vertigo is known to be caused by vertebrobasilar arterial occlusive disease
(ex. vertebrobasilar insufficiency; VBI), an electrophysiological study was
performed to examine the effects of a unilateral vertebral artery (VA) occlusion
on the neuronal activities of the medial vestibular nucleus (MVN) and vestibular
ganglion (VG) in alpha-chloralose-anesthetized cats. Single neuronal activity in
the MVN and VG was recorded extracellularly with a glass-insulated silver wire
microelectrode. When the unilateral VA was occluded for 5 min. the spontaneous
firing rate in the MVN was altered as follows. The type A pattern exhibited a
transient increase, followed by a decrease. The type B pattern showed a gradual
decrease, and no further changes after the onset of occlusion. Type A and B
patterns were observed respectively in MVN ipsi- and contra-lateral to the VA
occlusion. In contrast, the VG neuronal firing rate was not affected by the
occlusion. These results seem to support the clinical suggestion that the vertigo
in VBI is produced by a difference in the function between the bilateral
vestibular nuclei. rather than by the peripheral vestibular nerve.
PMID- 9657308
TI - Hemodynamics of a simulation of the vertebrobasilar system using silicone tube.
AB - We investigated the hemodynamics of the vertebrobasilar system (VBS) using a
simulation model tube made of silicone which had different diameters between the
bilateral vertebral artery (VA) ducts (stenotic and normal VA ducts). Using the
ultrasonic Doppler method. the laterality index (L.I.) of the flow velocity in
the VA duct was 32.88%. The flow volume of the anterior inferior cerebellar
artery duct and the posterior inferior cerebellar artery duct also had
significant laterality. By investigating the effects of the rotatory pulse rate
and fluid viscosity, a maximal decrease to below 40-50% of the flow volume of the
branches, and to below 71.93% in the mean flow velocity of the basilar artery
(BA) duct (BA duct) were observed. and the maximum L.I. increased to 43.15%. When
the unilateral stenotic VA duct was occluded by clamping (clamping occlusion),
the flow volume profiles of the branches were the same as without clamping
occlusion. The L.I. showed no significant changes and the maximal decrease in the
mean flow velocity of the BA duct was 68.61%. Using the laser Doppler method, the
flow velocity distribution of the BA duct was shifted towards the side of the
stenotic VA duct. These results suggest that the rheological dynamics in the main
vessels can certainly reflect the posterior circulatory dynamics, and that
modulating factors also aggravate the hemodynamics of the VBS with this disorder.
PMID- 9657309
TI - Inner ear blood flow in the rat after unilateral arterial occlusion in the
vertebrobasilar arterial system.
AB - It is generally accepted that certain kinds of vertigo and hearing disturbances
are caused by blood flow insufficiency in the vertebrobasilar arterial system.
Using the microsphere method we investigated whether unilateral vertebral artery
or unilateral posterior inferior cerebellar artery occlusion could cause an
imbalance between right and left inner ear blood flow in rats. We also studied
the differential vulnerability between blood flow in the cochlea and in the
ampullae of the three semicircular canals. We counted the numbers of microspheres
distributed to the cochlea (CO) and microspheres distributed to three ampullae of
semicircular canals (SC) under a microscope with the surface preparation method.
The results were as follows: i) no imbalances were observed between bilateral CO
or SC even in animals with arterial occlusion, and ii) the CO/SCs of animals with
arterial occlusion were not significantly different from that of the control
animals. These findings suggest that total inner ear blood flow over a certain
period of time was even between the ears bilaterally even in animals with
arterial occlusion. The blood flow in the ampullae of the three semicircular
canals was not more or less affected by arterial occlusion than the blood flow in
the cochlea.
PMID- 9657310
TI - Influence of hyperlipidemia and smoking on age-related changes in caloric
response and pure-tone hearing.
AB - To examine the influence of hyperlipidemia and smoking on age-related changes in
caloric response and pure-tone hearing, a caloric test and pure-tone audiometry
were performed in 14 healthy volunteers and in 78 tinnitus patients without
subjective hearing loss. The patients were from 24 to 84 years of age, and were
divided into 4 groups: the no-risk group (N group), the smoking alone group (S
group), the hyperlipidemia alone group (L group), and the smoking plus
hyperlipidemia group (S-L group). Slow phase eye velocity of the caloric
nystagmus (SPEV) and average hearing level at high frequencies were compared
between the N groups and the other groups. There was a significant difference in
SPEV only between the N and S-L groups, but not in the hearing level. This
suggests that age-related changes in the caloric response be promoted by
atherosclerosis, unlike presbycusis.
PMID- 9657311
TI - Four cases of vertebrobasilar insufficiency.
AB - Four cases of vertebrobasilar insufficiency are reported. Case 1 was a 38-year
old man who felt a sudden onset of dizziness when he turned his head to the back.
An abnormal positional nystagmus was observed when he rotated his head to the
left. A magnetic resonance angiogram (MRA) demonstrated total occlusion of the
left vertebral artery (VA). Case 2 was a 31-year-old woman who had a total
occlusion of her left VA as observed in the MRA. Case 3 was a 68-year-old man who
noted dizziness. The systolic blood pressure change on his Schellong test was 28
mmHg. On his MRA, severe displacement of the basilar and the vertebral arteries
was visible. Case 4 was a 76-year-old woman who noted a blackout-like sensation.
Optokinetic nystagmus was noted with a hyponystagmus pattern, and an eye tracking
test showed a saccadic pattern. On her MRA, the vertebrobasilar system was
narrowed. The arterial architecture and any stenosis of the blood vessels could
be detected non-invasively by MRA.
PMID- 9657312
TI - MR-angiographic findings of patients with central vestibular disorders.
AB - Magnetic resonance angiography (MRA) is a new, noninvasive, and useful method to
estimate the posterior circulation in patients with vertigo. From June 1995 to
May 1997, 180 patients were examined by magnetic resonance imaging (MRI) and MRA
in our department. One hundred and forty-seven patients were vertiginous
patients. We measured the displacement angle of the basilar artery with MRA, and
examined the relationship between the findings from some neurological
examinations and MRA findings in patients with vertigo and dizziness. One hundred
and forty-seven patients with vertigo or dizziness were examined by MRI and MRA.
They were diagnosed with MRI images in addition to several neurological
examinations. MRA was not used for the diagnosis but rather for measuring the
displacement angle of the basilar artery. Eighty-six cases with central
vestibular disorders, 11 cases with vertebrobasilar insufficiency, and 26 cases
with autonomic nerve disorders were recognized. In the cases of central
vestibular disorders, the incidences of hyperlipidemia and hypotension were
higher than the incidence of anemia. The average displacement angle of the
basilar artery (n = 180) was 153.4 degrees +/- 39.4 degrees (mean +/- S.D.). MRA
findings were classified into five categories. Ten patients were classified as
category III, which represented unilateral partial vertebral artery stenosis. The
detection rate for category III and IV abnormalities by neurological examination
was higher than that for the other categories. MRI and MRA are important methods
to examine patients with central nervous disorders. Distal vertebral artery
stenosis may carry a higher risk of a stroke than brainstem infarction.
PMID- 9657313
TI - Magnetic resonance imaging (MRI) test in hemodynamic vertebro-basilar
insufficiency.
AB - We investigated the efficiency of analysis by magnetic resonance imaging (MRI) in
cases of hemodynamic vertebro-basilar insufficiency (VBI). We enrolled 76 cases
of hemodynamic VBI who had visited our clinic in the Department of
Otolaryngology, Nara Medical University, from 1994 to 1996. The evaluation of MRI
was classified according to the degree of ventricular dilatation, callosal
degeneration, and lacunar infarction, and the evaluation of MR angiography (MRA)
was classified according to the degree of pathological change of the blood
vessels. There was a significant difference in lacunar infarction on the MRI
findings between VBI cases and normal controls, and there were also significant
differences in side differences in the vertebral artery between VBI cases and
peripheral vertigo and normal control patients. We propose an etiology for
hemodynamic VBI: a functional cerebral circulation disorder causes ischemia of
the basal ganglia and leads to lacunar infarctions; furthermore, the side
difference between the two vertebral arteries causes a circulation disorder in
the vertebrobasilar system.
PMID- 9657314
TI - Radiation-induced cancers of the head and neck region.
AB - A total of 65 patients with radiation-induced cancers of the head and neck region
were treated and evaluated. The primary disease for which the radiotherapy had
been applied was benign disease in 48 patients (including tuberculous
lymphadenitis in 39 patients), and malignant tumors in 17 patients (including 9
laryngeal cancers and 5 thyroid cancers). The radiation-induced cancers included
35 cases of hypopharyngeal cancer, 15 of thyroid cancer, and 13 of cervical
esophageal cancer. The mean duration from radiotherapy until the diagnosis of
cancer was 12.8 years in the patients with malignant primary tumor and 32.9 years
in those with benign primary diseases. Most of the patients underwent surgery for
their cancer. The clinical course was poor and the outcome extremely poor,
especially in those patients with field carcinogenesis. It is emphasized that
excessively high dosage and wide radiation field should be avoided, and that
radiotherapy for young patients with malignancies requires extremely careful
management.
PMID- 9657315
TI - Structure of the O-specific polysaccharide of Proteus penneri strain 41 from a
new proposed serogroup O62.
AB - O-specific polysaccharide of Proteus penneri strain 41 was studied using 1H- and
13C-NMR spectroscopy, including two-dimensional COSY, heteronuclear 13C,1H
correlation (HETCOR) and one-dimensional NOE spectroscopy, and the following
structure of a non-stoichiometrically O-acetylated hexasaccharide repeating unit
was established:[structure: see text] where RGlcNAc is 2-acetamido-4-O-[(S)-1
carboxyethyl]-2-deoxyglucose. Cross-reactivity of anti-P. penneri 41 O-serum with
other P. penneri strains is discussed, and a new, separate O62 serogroup is
proposed which is the next Proteus O-serogroup containing P. penneri strains
only.
PMID- 9657316
TI - Rhodococcus equi infection of monocytes/macrophages from human immunodeficiency
virus (HIV)-infected patients and healthy individuals: evaluation of
intracellular killing and nitric oxide production.
AB - Monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients
had a defect in their ability to kill Rhodococeus equi in vitro, as compared with
healthy HIV-seronegative individuals. Virulent and avirulent R. equi strains
isolated from humans and horses showed no significant intracellular replicative
differences within both HIV-positive and -negative monocytes/macrophages.
Infection with R. equi induced the production of nitric oxide (NO) by
monocytes/macrophages from healthy individuals, but not by cells from HIV
positive patients. The NO formation was significantly inhibited by L-NG
monomethyl arginine and arginase. However. neither competitive inhibition of NO
synthesis from L-arginine with L-NMMA nor depletion of arginine with arginase
altered the killing activity of human monocytes/macrophages against R. equi, thus
suggesting that L-arginine:NO pathway is not required for the intracellular
antirhodococcal mechanisms of human monocytes/macrophages.
PMID- 9657318
TI - Evaluation of the antimicrobial effect of lactoferrin on Porphyromonas
gingivalis, Prevotella intermedia and Prevotella nigrescens.
AB - The antimicrobial effect of lactoferrin (apoLf) on the oral, black-pigmented
anaerobes Porphyromonas gingivalis, Prevotella intermedia and P. nitrescens has
been studied. ApoLf did not kill any of these species but it did inhibit the
growth of P. gingivalis, while iron-saturated Lf (FeLf) had no effect. The other
two species were unaffected by apoLf. This growth inhibitory effect of apoLf
could not be explained on the basis of chelation of inorganic iron, since growth
of P. gingivalis occurred in the presence of ethylenediamine di-o
hydroxyphenylacetic acid provided haemin was added. Both apoLf and FeLf reduced
haemin uptake by all three species and caused the release of cell-bound haemin in
a dose-dependent manner. In addition, haemin reduced the binding of both apoLf
and FeLf to P. intermedia and P. nigrescens but stimulated the binding of Lf by
P. gingivalis. These data suggest that Lf forms complexes with haemin in solution
and competes for the binding of haemin to certain cell receptors, possibly
lipopolysaccharides, but this is not sufficient to inhibit growth of the
bacteria. P. gingivalis appears to bind Lf-haemin complexes, as well as haemin
alone, which may facilitate access of the Lf to the outer and cytoplasmic
membranes of P. gingivalis, so disrupting function.
PMID- 9657317
TI - Protective efficacy of mycobacterial 71-kDa cell wall associated protein using
poly (DL-lactide-co-glycolide) microparticles as carrier vehicles.
AB - Microparticles composed of poly (DL-lactide-co-glycolide) (DL-PLG) were used as
delivery vehicles for evaluating the immunoreactive and immunoprotective
properties of 71-kDa cell wall associated protein of Mycobacterium tuberculosis
H37Ra. Mice immunized with 71-kDa microparticles entrapped in DL-PLG (PLG-MPs)
exhibited significantly higher T-cell stimulation and cytokine release in
comparison to 71-kDa emulsified in Freund's incomplete adjuvant (FIA) as well as
a BCG vaccinated group throughout the post-immunization (p.im.) period. Further,
the protective efficacy of 71-kDa was evaluated on the basis of survival rates
and viable bacilli load in different organs at 30 days post challenge (p.c.),
with the median lethal dose (LD50) of M. tuberculosis H37Rv at weeks 8 and 16
p.im. Both 71-kDa-PLG and 71-kDa-FIA immunized groups exhibited a comparable
protection (90%) which was significantly higher (P < 0.5) than in the BCG group
(70%) at week 8 p.im. and it was consistent with the decreased bacterial load in
the target organs. However, on increasing the interval of challenge to 16 weeks
p.im., the protective efficacy of 71-kDa-PLG was sustained (85%) while that of 71
kDa-FIA began to wane (70%). Further. the 71-kDa-PLG immunized group exhibited a
significantly higher (P < 0.001) clearance of bacterial load from the lungs and
livers in comparison to the 71-kDa-FIA immunized group. The results suggest the
long-term protective potential of a PLG-microparticle based antigen delivery
system for tuberculosis.
PMID- 9657319
TI - Altered expression of constitutive type and inducible type heat shock proteins in
response of D-galactosamine-sensitized mice to lipopolysaccharide as an
experimental endotoxic shock model.
AB - The expression of heat shock proteins (HSPs) as stress-induced proteins was
studied in mice injected with D-galactosamine (D-GalN) and lipopolysaccharide
(LPS) as an experimental endotoxic shock model. The expression of constitutive
type heat shock protein 70 (HSC70) was significantly reduced in livers of mice
injected with D-galactosamine and lipopolysaccharide, while its expression was
unaffected in livers of mice injected with D-galactosamine or lipopolysaccharide
alone. The expression of other constitutive type heat shock proteins, namely
HSP60, HSP32 and HSP25 was also reduced in mice injected with D-galactosamine and
lipopolysaccharide. On the other hand, inducible type HSP70 was detected in
livers from mice injected with D-galactosamine and lipopolysaccharide, but not in
livers from mice injected with D-galactosamine or lipopolysaccharide alone.
Simultaneous injection of anti-tumor necrosis factor (TNF)-alpha antibody
prevented the liver from reduced expression of constitutive type HSC70, and lead
to marked expression of inducible type HSP70 in the liver. Reduced expression of
constitutive type HSC70 was also found when D-galactosamine and recombinant TNF
alpha was injected. Therefore, TNF-alpha was suggested to play a critical role on
altered expression of constitutive HSC70 and inducible type HSP70 in response of
D-galactosamine-sensitized mice to lipopolysaccharide.
PMID- 9657320
TI - Rare, suppurative pulmonary infection caused by Nocardiopsis dassonvillei
recognized by glycolipid markers.
AB - An opportunistic actinomycete was isolated as the only etiological agent of a
severe, suppurative pulmonary infection. The strain was rapidly recognised as
Nocardiopsis by the taxonomically important and immunologically active glycolipid
markers (G1 and G2). Identification of the clinical isolate, from a group of
actinomycetes mainly known as soil habitants, was definitely proved by
chemotaxonomic studies (cell wall/sugar, phospholipid and fatty acid types) as
well as by genomic data (GC content, DNA-DNA reassociation). The level of DNA-DNA
homology of the clinical actinomycete, in comparison with other reference members
of this genus, revealed the highest (88%) relatedness to Nocardiopsis
dassonvillei. The results confirmed the value and generic specificity of
glycolipid markers from Nocardiopsis, the first time used for rapid recognition
of a clinical strain causing a nocardiosis-like disease.
PMID- 9657321
TI - Phospholipid molecular species distribution of oral Prevotella corporis clinical
isolates.
AB - The aim of this study was to determine the distribution of phospholipid molecular
species within Prevotella corporis of oral origin. Phospholipids of fresh
clinical isolates were extracted and analysed by fast atom bombardment mass
spectrometry (FAB-MS) in negative-ion mode. The major monocarboxylate anion
peaks, with putative identification, observed for Prevotella corporis were m/z
241, C(15:0); 255, C(16:0); 269, C(17:1); 277, C(18:3); 279, C(18:2); 281,
C(18:1). In the high mass region, major anion peaks putatively identified as
individual phospholipid (PL) molecular species of Prevotella corporis were of m/z
677, PG(29:1); 691, PG(30:1); 705, PG(31:1); 706, first isotope peak of PG(31:1);
and 707, PG(31:0). Related species have a different distribution of PL analogues.
Separation of extracted lipid families by TLC confirmed that
phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) are the major polar
lipids (PLs) in Prevotella corporis. Thus Prevotella corporis has a unique
combination of phospholipid analogues of chemosystematic significance.
PMID- 9657322
TI - Psoriasis patients have T-cells with reduced responsiveness to common
mycobacterial antigens.
AB - Heparinised blood samples were obtained from 20 patients with chronic plaque
psoriasis and from 13 age-matched healthy controls. After preliminary titration,
mononuclear cells separated over Ficoll-Tryoson were cultured for 5 days with 10
microg ml(-1) of 15 mycobacterial preparations, or with pokeweed mitogen and
concanavalin A. Stimulation indices were determined for each reagent and means
were determined for patients and controls. Results for patients showed a striking
reduction of responsiveness to mycobacteria, apparently due to loss of responses
to group i, common mycobacterial antigens, and no differences in responses to
mitogens. These observations relate psoriasis to certain other diseases, notably
mycobacterial infections, rheumatoid arthritis, Chagas' disease and human
immunodeficiency virus infection. The observations may be relevant to the
aetiology of psoriasis, and to potential immunotherapy for the disease.
PMID- 9657323
TI - Immunotherapy with Mycobacterium vaccae in the treatment of psoriasis.
AB - A placebo-controlled study of immunotherapy with Mycobacterium vaccae for chronic
plaque psoriasis showed improvement in the psoriasis area severity index in 19 of
21 immunotherapy recipients (P<0.005). Minor improvement, not reaching
statistical significance for the group, occurred in nine of 14 placebo
recipients. There were losses to follow-up and the placebo used, tetanus toxoid,
was not ideal. Clinical improvement after immunotherapy persisted for 6 months
and another injection of the immunotherapeutic given to a few volunteers from
either group resulted in benefits lasting a year. Lymphoproliferative tests were
carried out at each clinic visit, and on 50 matched controls. Starting with
reduced responses to mycobacterial antigens and concanavalin A, both treatment
groups showed a fall after 3 months, and diverged at 6 months with M. vaccae
recipients rising to values similar to those of healthy controls, whereas placebo
recipients continued to fall. Conclusions reached were that immunotherapy with M.
vaccae gave long-lasting clinical benefit to most patients, with minimal side
effects. This accompanied a return towards normal cellular immune responsiveness
to mycobacterial antigens, which did not follow the use of the placebo.
PMID- 9657324
TI - Effect of O-antigenic polysaccharide of Escherichia coli on endotoxin
neutralizing activity of lysozyme.
AB - Endotoxemia is considered to be associated with the high mortality of gram
negative septic patients. Increasing evidence shows that beta-lactam antibiotics
have a propensity to induce endotoxin release from the bacterial outer membrane
while killing bacteria. We have recently found that egg white lysozyme (EW-LZM)
shows strong inhibition of beta-lactam induced bacteriolysis and
lipopolysaccharide (LPS) release from Escherichia coli O111, resulting in
reduction of the LPS-initiated inflammatory response. In this study, we compared
the effect of EW-LZM on E. coli J5, which possesses rough-type LPS (RaLPS), in
order to demonstrate the effect of O-antigenic polysaccharide on endotoxin
neutralizing activity of EW-LZM and on inhibition of beta-lactam induced lysis by
LZM. Both of the beta-lactam induced bacterial lysis and subsequent LPS release
were almost completely inhibited by EW-LZM. The effect was more potent than that
of wild-type LPS as assessed by released LPS concentration and LPS induced
cytokine syntheses. In addition, EW-LZM was effective against lethal infection of
E. coli J5 in cyclophosphamide induced leukopenic mice. These facts strongly
suggested that O-antigenic polysaccharide negatively modulates LPS neutralizing
activity of EW-LZM.
PMID- 9657325
TI - Isolation, characterization and disruption of the casein kinase II alpha subunit
gene of Leishmania chagasi.
AB - To elucidate the role played by casein kinase II in Leishmania survival, we have
isolated and characterized the Leishmania chagasi casein kinase II alpha subunit
cDNA, (L.c CKIIalpha). The 1083 bp coding region is flanked by 148 bp of 5' UTR
and 1155 bp of 3' UTR. L.c CKIIalpha shows a remarkable degree of similarity with
other isolated casein kinase II alpha subunit sequences. L.c CKIIalpha protein is
encoded by a single copy gene that transcribes a mRNA of 2.4 kb. The 41.2 kDa L.c
CKIIalpha protein expressed in vitro has been shown to be catalytically active. A
single allele disruption of the L.c CKIIalpha gene that removes 94 bp from the
coding region which contains one of the 15 conserved amino acids closest to the
carboxy-terminus of the protein has been generated. This mutant is viable and
results in a reduction of L.c CKIIalpha transcript levels over 14-fold and that
of an iron superoxide dismutase mRNA by 5-fold. As well, the kinase activity of
the single allele disrupted cells showed a 3-fold reduction as compared to the
wild type cells suggesting a decrease in activity of the L.c CkIIalpha enzyme.
PMID- 9657326
TI - Nuclear antigens in Trichinella spiralis infected muscle cells: nuclear
extraction, compartmentalization and complex formation.
AB - Infection of mammalian skeletal muscle cells by Trichinella spiralis induces a
series of changes that include: reentry of the terminally differentiated host
cell into the cell cycle; suspension of infected cells in apparent G2/M; and
transcriptional inactivation of the differentiated skeletal muscle gene program.
Cell cycle repositioning and genetic reprogramming are chronic characteristics of
host cells that can remain infected for years. Nuclear antigens (NA, 79, 86 and
97 kDa) that localize to host cell nuclei have been detected with antibodies
against T. spiralis proteins. Since NA may play a role in regulating the infected
cell phenotype, their origin, nuclear compartmentalization, and biochemical
properties were investigated. We show that a monoclonal antibody to a defined
epitope of T. spiralis glycans binds these NA, which indicates the parasite
origin of these proteins. NA were not extracted under conditions that solubilized
chromatin from infected cell nuclei. In contrast, NA were coextracted with B
lamins (nuclear envelope) by 4 M urea. Urea extraction was pH dependent (8.0),
suggesting ionic interaction of NA in protein complexes. Nevertheless, confocal
microscopy demonstrated colocalization of NA with host chromatin, and not B
lamins. Nuclear protein complexes containing NA were observed under non-reducing
conditions, and NA were readily cross-linked in isolated nuclei by succinimidyl
protein conjugating reagents. The results establish methods to extract NA from
infected cell nuclei for further biochemical analysis, establish the existence of
nuclear protein complexes containing NA and demonstrate colocalization of NA with
host chromatin. Collectively, the results provide a foundation from which to
investigate the role of NA in regulating the T. spiralis infected skeletal muscle
cell phenotype.
PMID- 9657327
TI - Relation between variation in copy number of ribosomal RNA encoding genes and
size of harbouring chromosomes in Leishmania of subgenus Viannia.
AB - Chromosomal size polymorphism in Leishmania of subgenus Viannia has been
correlated with eco-geography. The sizes of chromosomes bearing rDNA genes were
determined in 69 isolates. A considerable size-variation was observed, ranging
from 1100 to 1500 kb. Chromosomes of L.(V.). braziliensis, L.(V.)guyanensis and
L.(V.) peruviana from northern Peru were significantly larger (200 kb) than those
of L.(V.) peruviana from southern Peru. In addition, 31 out of 69 isolates
presented each two different-sized homologues of the rDNA chromosome. Long range
restriction mapping of three different-sized rDNA chromosomes from
L.(V.)braziliensis M2903 and L.(V.)peruviana HB31 (north) and LC106 (south) each
revealed three fragments delimited by PmeI restriction sites: two constant in
size (the centre and one extremity of the chromosome) and one variable (the other
extremity, containing a single cluster of rDNA genes). Further analysis of the
M2903 rDNA chromosome allowed the localization of its 140 kb rDNA cluster at 85
kb from the telomeric end. Two arguments indicated that size-variation of the
rDNA chromosome is partially due to amplification/deletion of the clustered rDNA
genes: (i) size-variation of the cluster-containing fragment was proportional to
the size-variation of the whole chromosome, and (ii) hybridization signal
intensity of the rDNA chromosome with a small subunit rDNA probe strongly
correlated with chromosomal size. Nevertheless, DNA sequences present between the
rDNA cluster and the telomere might also play a role in chromosomal size
polymorphism. In addition, our data suggest that rDNA gene copy number (20-40
copies cell(-1) under a diploid hypothesis) in subgenus Viannia is lower than
reported previously.
PMID- 9657328
TI - Upstream elements required for expression of nucleoside triphosphate hydrolase
genes of Toxoplasma gondii.
AB - Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate
protozoan parasite Toxoplasma gondii. The protein has apyrase activity, degrading
ATP to the di- and mono-phosphate forms. Because T. gondii is incapable of de
novo synthesis of purines, it is postulated that NTPase may be used by the
parasite to salvage purines from the host cell for survival and replication. To
elucidate the molecular mechanisms of NTP gene expression, we isolated from the
virulent RH strain of T. gondii the putative promoter region of three tandemly
repeated NTP genes (NTP1, 2, 3). Using deletion constructs linked to the
chloramphenicol acetyl transferase (CAT) reporter gene, we defined an active
promoter within the first 220 bp. Sequence analysis of this region reveals the
lack of a TATA box, but the promoter region is associated with a sequence which
resembles an initiator element (Inr) in the NTP1 and NTP3 genes. This sequence
which is similar to other Inrs known to regulate the expression of a wide variety
of RNA polymerase II genes, is required for NTP expression. The NTP3 promoter
contains sufficient information for developmentally regulated expression of CAT
activity when the actively replicating stage tachyzoite differentiates into the
dormant bradyzoite form.
PMID- 9657329
TI - Predicted and observed alleles of Plasmodium falciparum merozoite surface protein
1 (MSP-1), a potential malaria vaccine antigen.
AB - The 19-kDa antigenic domain of Plasmodium falciparum merozoite surface protein
(MSP)-1 is a potential malaria vaccine candidate. Based on the amino acid
substitution, four known alleles, E-TSR (PNG-MAD20 type), E-KNG (Uganda-PA type),
Q-KNG (Wellcome type), and Q-TSR (Indo type) of this domain have been identified.
Using single or double crossover recombinational events, we predicted the
existence of additional alleles of this antigen. The presence of the predicted
alleles was determined in parasite isolates from western Kenya, by undertaking a
cross-sectional and a longitudinal study. Of the ten predicted alleles, we have
revealed the presence of three new alleles: E-KSG-L (Kenya-1 type); E-KSR-L
(Kenya-2 type); and E-KNG-F (Kenya-3 type). The results of this study suggest
that it may be possible to predict the complexity of the genetic makeup of
natural parasite populations.
PMID- 9657330
TI - A phylogenetic analysis of the Trypanosoma cruzi genome project CL Brener
reference strain by multilocus enzyme electrophoresis and multiprimer random
amplified polymorphic DNA fingerprinting.
AB - We have assessed the phylogenetic status of the Trypanosoma cruzi Genome Project
CL Brener reference strain by multilocus enzyme electrophoresis (MLEE) and
multiprimer random amplified polymorphic DNA (RAPD) including a set of cloned
stocks representative of the whole genetic diversity of T. cruzi. MLEE and RAPD
data gave congruent phylogenetic results. The CL Brener reference strain fell
into the second major phylogenetic subdivision of T. cruzi, and was genetically
very close to the Tulahuen reference strain. No reliable RAPD character and only
one MLEE character permitted us to distinguish between the CL Brener and Tulahuen
reference strains. In contrast, many RAPD and MLEE characters were able to
distinguish between the CL Brener reference strain and the other T. cruzi
genotypes analyzed here, in particular the formerly described principal zymodemes
I, II and III. It is suspected that both CL Brener and Tulahuen are hybrid
genotypes, a fact that should be taken into account when interpreting sequence
data. Moreover, our study confirms that the species T. cruzi is genetically very
heterogeneous. We recommend future comparison of sequencing data from the CL
Brener reference strain with those of at least one radically distinct T. cruzi
genotype, belonging to the other major phylogenetic subdivision of this species.
PMID- 9657331
TI - Sequence variations in the Plasmodium vivax dihydrofolate reductase-thymidylate
synthase gene and their relationship with pyrimethamine resistance.
AB - The gene encoding dihydrofolate reductase-thymidylate synthase of the human
malaria parasite, Plasmodium vivax, was isolated by polymerase chain reaction
from genomic DNA and cloned. The sequences of the dihydrofolate reductase domain
of 30 clinical isolates originating from various geographic areas were compared.
Interstrain analysis revealed several genotypic variations, including short
tandem repeat arrays which produced length polymorphism between different
parasite isolates and point mutations in the putative dihydrofolate reductase
active site cavity corresponding to those associated with pyrimethamine
resistance in P. falciparum and rodent malaria parasites. Amino acid
substitutions Ser-->Asn-117 and Ser-->Arg-58 were associated with decreased level
of in vitro pyrimethamine sensitivity. These findings suggest that the P. vivax
dihydrofolate reductase domain is characterized by polymorphism that has not been
observed in P. falciparum and may explain the resistance of some P. vivax
isolates to pyrimethamine. Nucleotide sequence data reported in this paper are
available in the EMBL, GenBank and DDJB databases under the accession numbers
X98123 (isolate ARI/Pakistan), AJ003050 (isolate CNC/Thailand), AJ003051 (isolate
COU/unknown geographic origin), AJ003052 (isolate DUF/French Guiana), AJ003053
(isolate GRO/Madagascar), AJ003054 (isolate HRT/Comoros Islands), AJ003071
(isolate LFT/Cambodia), AJ003072 (isolate LGF/'India), AJ003073 (isolate
MAN/Comoros Islands), AJ003074 (isolate MAT/Surinam), AJ003075 (isolate
PHI/Djibouti), AJ003076 (isolate PIT/Madagascar), AJ003077 (isolate
YTZ/Indonesia), AJ222630 (isolate Burma-1), AJ222631 (isolate Burma-151),
AJ222632 (isolate Burma-5), AJ222633 (isolate Burma-6), AJ222634 (isolate Burma
98).
PMID- 9657332
TI - Characterisation of Tc-cpl-1, a cathepsin L-like cysteine protease from Toxocara
canis infective larvae.
AB - Cysteine proteases play vital biological roles in both intracellular and
extracellular environments. A cysteine protease migrating at 30 kDa was
identified in somatic extracts of Toxocara canis larvae (TEX), by its binding to
the biotinylated inhibitor Phe-Ala-CH2F. TEX proteases readily cleaved the
cathepsin L- and B-specific peptide substrate Z-Phe-Arg-AMC and to a lesser
extent, the cathepsin B-specific peptide Z-Arg-Arg-AMC. Excretory/secretory (TES)
products of T. canis larvae did not cleave either substrate. Partial sequence
encoding the 5' end of a cysteine protease cDNA from infective T. canis larvae
was then obtained from an expressed sequence tag (EST) project. The entire cDNA
(termed Tc-cpl-1) was subsequently sequenced and found to encode a preproenzyme
similar to cathepsin L-like proteases (identities between 36 and 69%), the
closest homologues being two predicted proteins from Caenorhabditis elegans
cosmids, a cathepsin L-like enzyme from Brugia pahangi and a range of parasite
and plant papain-like proteases. Sequence alignment with homologues of known
secondary structure indicated several charged residues in the S1 and S2 subsites
involved in determining substrate specificity. Some of these are shared with
human cathepsin B, including Glu 205 (papain numbering), known to permit cleavage
of Arg-Arg peptide bonds. The recombinant protease (rTc-CPL-1) was expressed in
bacteria for immunisation of mice and the subsequent antiserum shown to
specifically react with the 30 kDa native protease in TEX. Sera from mice
infected with the parasite also contained antibodies to rTc-CPL-1 as did sera
from nine patients with proven toxocariasis; control sera did not. Larger scale
studies are underway to investigate the efficacy of rTc-CPL-1 as a diagnostic
antigen for human toxocariasis, the current test for which relies on whole
excretory/secretory antigens of cultured parasites.
PMID- 9657333
TI - Targeted disruption of the bradyzoite-specific gene BAG1 does not prevent tissue
cyst formation in Toxoplasma gondii.
AB - Expression of the 30 kDa small heat shock protein BAG1 is restricted to the
latent bradyzoite 'tissue cyst' form of Toxoplasma gondii, first appearing
approximately 2-3 days after the initiation of bradyzoite differentiation.
Although developmental expression of small heat shock proteins has been described
for many species, their precise function is unclear. In order to examine the
function of BAG1 in T. gondii bradyzoites and its role during parasite
differentiation, we have used homologous recombination to produce a knock-out
mutant in the cyst-forming strain P(LK), a clonal derivative of ME49. Under
tissue culture conditions that stimulate bradyzoite differentiation (alkaline
pH), the mutant was found to express several bradyzoite-specific markers with the
same kinetics and frequency as the parental strain. Neither enhanced nor
decreased susceptibility to stress was observed for the BAG1-deficient mutant. In
vivo studies revealed that tachyzoites of the bag1 knock-out mutant were fully
able to establish a chronic infection in C57BL/6 mice, producing brain cysts of a
size, morphology and frequency indistinguishable from cysts formed by the
parental control strain. Brain cysts of the bag1 knock-out mutant contained
viable parasites capable of establishing an acute infection after oral
administration, demonstrating that conversion of bradyzoites to tachyzoites is
also unimpaired. We conclude that BAG1 is not essential for normal function of
bradyzoite containing tissue cysts, at least in intermediate host species. This
clone of P(LK) was found to be unable to produce oocysts and is therefore
unsuitable for studies in cats.
PMID- 9657334
TI - A mutation scanning approach for the identification of hookworm species and
analysis of population variation.
AB - To overcome limitations in the morphological identification of different
developmental stages of hookworms to species, we have established a polymerase
chain reaction-linked single strand conformation polymorphism technique (PCR
SSCP) utilizing the internal transcribed spacers (ITS) of ribosomal (r)DNA. These
spacers were specifically chosen because they provide reliable species markers
for strongylid nematodes. ITS spacers were amplified by PCR from DNA derived from
individual parasites of seven species of hookworm, then denatured and subjected
to electrophoresis in a mutation detection enhancement (MDE) (non-denaturing) gel
matrix. PCR SSCP analysis showed that the single-strand ITS patterns produced
allowed the unequivocal identification of all species. The method also allowed
the direct display of sequence variation within some species where multiple
individual worms were examined. These findings demonstrate the usefulness of the
SSCP approach for hookworm identification, the detection of population variation
and the direct display of sequence variation in rDNA.
PMID- 9657335
TI - Control mechanisms of the H2A genes expression in Trypanosoma cruzi.
AB - In a previous report we have described that the T. cruzi histone H2A gene is
encoded in two independent gene clusters located in a single chromosome. In the
present paper we show that both gene cluster are actively transcribed as two
sized classes of polyadenylated mRNAs demonstrating, moreover, the existence of
alternative splicing sites and microheterogeneities at the polyadenylation site.
We also describe that while the expression of the H2A genes in the non
replicative trypomastigote forms is only residual, in the replicative forms there
is constitutive transcription of these genes and that the transcription is not
associated to DNA replication. The data show, moreover, that in the replicative
forms the steady state levels of the H2A mRNAs are controlled at a post
transcriptional level which is associated to DNA replication.
PMID- 9657336
TI - Expression, selection, and organellar targeting of the green fluorescent protein
in Toxoplasma gondii.
AB - We have engineered a mutant version of the green fluorescent protein GFP (Cormack
et al. Selected for bright fluorescence in E. coli. Gene 1996;173:33-38) for
expression in the protozoan parasite Toxoplasma gondii. Although intact GFP was
not expressed at any detectable level, GFP fusion proteins could be detected by
fluorescence microscopy, flow cytometry (FACS), and immunoblotting. Both
extracellular tachyzoites and T. gondii-infected host cells could readily be
sorted by FACS, which should facilitate a variety of selection strategies.
Several selectable markers were tested for their ability to produce stable green
transgenic parasites. Fluorescence intensity was directly correlated with gene
copy number and protein expression level. Weak selectable markers such as
chloramphenicol acetyl transferase (CAT) driven by the SAG1 promoter, which yield
multicopy insertions, are therefore most effective for selecting green
fluorescent parasites-particularly when coupled to constructs which employ a
strong promoter to drive GFP expression. Transformation vectors developed in the
course of this work should be of general utility for the overexpression of
heterologous transgenes in Toxoplasma. CAT-GFP fusion proteins were expressed in
the parasite cytoplasm. GFP fusions to the P30 major surface antigen (linked on
the same plasmid to a CAT selectable marker under control of various promoters)
could be detected in dense granules within living cells, and were efficiently
secreted into the parasitophorous vacuole. GFP fusions to the rhoptry protein
ROP1 were targeted to rhoptries (specialized secretory organelles at the apical
end of the parasite).
PMID- 9657337
TI - Ecto-protein tyrosine phosphatase activity in Trypanosoma cruzi infective stages.
AB - Live T. cruzi trypomastigotes and amastigotes possess ecto-protein tyrosine
phosphatase activity as indicated by the ability of intact cells to catalyze
dephosphorylation of tyrosine phosphorylated myelin basic protein,
[32P]TyrRaytide, phosphotyrosine, or the phosphotyrosine analog p
nitrophenylphosphate (p-NPP). The dephosphorylation of myelin basic protein (MBP)
and p-NPP was inhibited by sodium o-vanadate, zinc chloride and NaF, while
dephosphorylation of [32P]TyrRaytide was insensitive to zinc chloride but
sensitive to o-vanadate and NaF. In contrast, live cells were not able to
dephosphorylate serine or threonine phosphorylated peptides ([32P]Kemptide) or
proteins ([32P]RCM-lysozyme and [32P]MBP).
PMID- 9657338
TI - Variation in the thrombospondin-related adhesive protein (TRAP) gene of
Plasmodium falciparum from Thai field isolates.
PMID- 9657339
TI - Cloning and expression of the Entamoeba histolytica ERD2 gene.
PMID- 9657340
TI - Active site mutants of a cyclosporin A-insensitive cyclophilin from Brugia
malayi: effect on catalysis and drug binding.
PMID- 9657341
TI - Immunolocalization of Trypanosoma brucei hypoxanthine-guanine
phosphoribosyltransferase to the glycosome.
PMID- 9657342
TI - Follicle stimulating hormone international standards and reference preparations
for the calibration of immunoassays and bioassays.
AB - Follicle stimulating hormone is a dimeric glycoprotein hormone which is used
widely in reproductive and developmental medicine both as a diagnostic analyte
and as a therapeutic product. It is therefore a good example of a clinically
important heterogeneous material for which a number of different assay
methodologies have been developed. Immunoassays for follicle stimulating hormone
(FSH) are used in the diagnosis of disorders of reproduction and development,
whereas in vivo bioassays are used for calibration of therapeutic preparations.
Different immunoassay systems, based on different formats, exhibit variability in
their estimates of activity of FSH which arises from different specificities of
antibodies for different forms of FSH which are encountered. In order to minimise
between assay variation and to enable better between laboratory comparisons the
World Health Organisation (WHO) has issued a series of ampouled preparations of
FSH. The availability of these materials has been reviewed previously but on the
completion of a recent collaborative study to evaluate candidate standards for
rDNA-derived FSH and highly purified urinary FSH (urofollitropin) it is now
appropriate to review the current status of these standards and to discuss the
future of standardisation for FSH in particular and where appropriate to make
reference to other materials.
PMID- 9657343
TI - Qualitative bedside assay of increased human serum myoglobin by sandwich dot
immunogold filtration for the diagnosis of acute myocardial infarction.
AB - We isolated and purified myoglobin (MYO) from human fresh skeletal muscle and
prepared monoclonal and polyclonal antibody from it. A sandwich dot-immunogold
filtration assay (DIGFA) for the detection of MYO was developed by using affinity
purified sheep anti-MYO antibody as the first antibody for coating nitrocellulose
membranes (NCMs; the support) and colloidal gold labelled monoclonal antibody
(H3) as the second antibody (an indicator). The test can be completed in 3 min
without incubation or any equipment. A reddish dot, indicating positivity, is
obvious to the naked eye. No interferences from bilirubin, hemoglobin, rheumatoid
factors and lipid were found. In order to use undiluted serum, the detection
limit was set at 100 microg of MYO/l. Concentrations up to 30,000 microg/l can be
measured without getting a "hook" effect. Serum MYO levels in 53 patients with
acute myocardial infarction (AMI), 100 healthy individuals, seven patients with
chest pain but without myocardial ischemia and in 39 patients with renal
insufficiency were measured simultaneously by DIGFA and enzyme-linked
immunosorbent assay (ELISA). All serum samples from patients had MYO
concentrations above 100 microg/l by ELISA and were positive by DIGFA. Serum
creatinine values were related to MYO test results. Healthy individuals had MYO
levels below 85 microg/l by ELISA and were negative by DIGFA.
PMID- 9657344
TI - Specific determination of germ cell alkaline phosphatase for early diagnosis and
monitoring of seminoma: performance and limitations of different analytical
techniques.
AB - Two-dimensional electrophoresis, ion-exchange chromatography and immunoassay were
evaluated in order to improve the diagnostic specificity of the germ cell
specific isoenzyme of alkaline phosphatase (GCAP) for the detection of seminoma.
Assessment of GCAP is hampered by its structural heterogeneity and low serum
concentration. The structural heterogeneity of GCAP from seminoma tissue could be
clearly visualized by two-dimensional electrophoresis. We inferred that it
depended on allelic amino acid substitutions, varying sialylation and
differential cleavage of the membrane anchor. The allelic variability of GCAP
affects the accuracy of immunological measurements. However, immunoassay was
found to be the only technique sensitive enough to assess GCAP in serum. The
elevated GCAP levels in 15% of healthy blood donors were shown to be correlated
with smoking. Further studies clarifying how to interpret the values measured in
smokers are prerequisite for the introduction of GCAP as a serum marker for
seminoma. In the future, GCAP might be utilized for the detection of carcinoma in
situ (CIS) cells in ejaculate. Assessment of the enhanced expression of cellular
GCAP by CIS cells exfoliated into ejaculate could be a means for noninvasive,
early diagnosis that presumably will not be hampered by the patient's smoking
habits.
PMID- 9657345
TI - A non ouabain-like inhibitor of the sodium pump in uremic plasma ultrafiltrates
and urine from healthy subjects.
AB - A non ouabain-like inhibitor of the sodium pump was separated from uremic plasma
ultrafiltrates and normal urine. Under the same chromatographic conditions (C18
column and a gradient of acetonitrile as eluant), ouabain was eluted in a
fraction different from the inhibitor. Affinity chromatography based on the
formation of a complex between Na,K-ATPase and the inhibitor achieved the
differentiation ouabain. Without magnesium and sodium phosphate, ouabain could
not bind to enzyme whereas the inhibitor did. A study of Na,K-ATPase enzyme
kinetics showed the inhibitor was not competitive for K+, which further
differentiates it from ouabain. It was uncompetitive for ATP and seemed
competitive for Na+. These results indicate that the inhibitor acts inside the
cell, unlike ouabain, and thus its action mechanism appears to be original.
PMID- 9657346
TI - Metabolic studies in a patient with severe carnitine palmitoyltransferase type II
deficiency.
AB - Here we report on a patient with severe ("non-classic") carnitine
palmitoyltransferase type II (CPT II) deficiency. Hypoglycemia prompted by an
infectious episode and associated with non-ketotic dicarboxylic aciduria
orientated diagnosis towards beta-oxidation deficiency disorders. Blood carnitine
levels revealed a secondary carnitine deficiency that was responsive to oral L
carnitine supplementation. Blood acylcarnitine profiles were abnormal and
included acetyl (C2:0), butyryl/isobutyryl (C4:0), isovaleryl/2-methylbutyryl
(C5:0), hexanoyl (C6:0), myristoyl (C14:0), palmitoyl (C16:0), hexadecenoyl
(C16:1), oleyl (C18:1) and stearoyl (C18:0) carnitine. In urine, excess excretion
of dicarboxylylcarnitines, mainly dodecanedioylcarnitine, was noticed. Upon
carnitine supplementation, C8 to C12 fatty acylcarnitines, with decanoylcarnitine
as well as C10 to C14 dicarboxylylcarnitines being prominent, were observed in
urine. Biochemical measurements disclosed a severe reduction of mitochondrial CPT
II activity (7% of normal values). Correlations of metabolic findings in the
patient and physiological roles of CPT II are briefly discussed.
PMID- 9657347
TI - Improved fluorometric enzymatic sorbitol assay in human blood.
AB - Samples for use in the fluorometric enzymatic assay of sorbitol in erythrocytes
are normally prepared using HClO4 and K2CO3. We have replaced these reagents with
NaOH and ZnSO4. Human whole blood, erythrocyte and plasma samples prepared with
NaOH and ZnSO4 are colorless and clear, while erythrocyte samples prepared with
HClO4 and K2CO3 are a pale yellow-brown color. The sorbitol dehydrogenase
reaction in the supernatant of the mixture of NaOH and ZnSO4 is inhibited, but
ethylenediaminetetraacetate completely eliminates this effect. The sorbitol assay
in erythrocytes prepared with NaOH and ZnSO4 shows higher sensitivity and
reproducibility than did that with HClO4 and K2CO3. Recovery of sorbitol added to
erythrocytes is similar in both assay methods. Concentrations of whole blood and
erythrocyte sorbitol assayed by the present method are significantly higher in
diabetics than in normals. Poorly controlled diabetics had higher whole blood and
erythrocyte sorbitol than well-controlled diabetics. Whole blood sorbitol
concentrations differed more between diabetic and normal subjects than did
erythrocyte sorbitol concentrations.
PMID- 9657348
TI - Human pancreatic reg protein immunoenzymatic assay and molecular form in serum.
AB - A direct sandwich immunoassay was developed to quantify the human reg protein, a
non enzymatic pancreatic acinar protein the biological function of which remains
elusive. Polystyrene balls were coated with specific IgG fraction as the first
antibody and horseradish peroxidase labelled IgG was used as a second antibody.
The linearity of the assay was good over a concentration range of 1.25-100 ng/ml
and the good parallelism obtained between the standard and the assay dilution
curves in serum and pancreatic juice indicates the absence of non-specific
interfering reactions. Gel filtration of serum showed that the reg protein was
eluted in the fractions corresponding to the proteins of around 25 kDa and that
the chromatographic behaviour of the serum protein was identical to that of the
purified pancreatic protein when added to serum. This assay was simple, specific,
sensitive and reproducible and may permit the determination of low levels of reg
protein in different biological fluids.
PMID- 9657349
TI - Blood glutamate levels in patients with motor neuron disease.
AB - This study was undertaken to evaluate the role of excitatory amino acid glutamate
(Glu) in the pathophysiology of motor neuron disease (MND). It was observed that
blood Glu levels were significantly higher in MND patients with respect to
healthy controls. The data indicate that Glu homeostasis is altered in the
patients with MND.
PMID- 9657350
TI - Lipid profile in various phases of menstrual cycle and its relationship with
percentage plasma volume changes.
PMID- 9657351
TI - Sialic acid content of von Willebrand factor subunit. A simple method for
quantitative estimation.
PMID- 9657352
TI - Sensory CGRP depletion by capsaicin exacerbates hypoxia-induced pulmonary
hypertension in rats.
AB - Pulmonary hypertension is a debilitating disease that occurs among infants and
adults. One of many etiologies is airway hypoxia. We previously demonstrated a
role of endogenous calcitonin gene-related peptide (CGRP), a potent vasodilator,
in ameliorating the pulmonary vascular pressor response to chronic hypoxia and
related changes in the lungs and heart. This study evaluates the role of
endogenous sensory CGRP in hypoxic pulmonary hypertension and examines the
intrinsic neural microcircuitry. Rats were pretreated with capsaicin i.p. to
deplete pulmonary sensory C-fiber stores of CGRP and substance P and placed in
hypobaric hypoxia (10% O2, 16 days) or normoxia together with sham controls.
Hypoxia increased pulmonary artery pressure, right-ventricular weight, arterial
medial thickness, elasticized capillaries, endothelial cell density, lung water
and hematocrit in control rats. Capsaicin augmented pulmonary artery pressure and
right-ventricular hypertrophy in hypoxia, and medial thickness and endothelial
cell density both in normoxia and hypoxia. Because of the limited effects on
these parameters by substance P and other capsaicin-sensitive lung agents, our
results suggest that sensory CGRP deficit severely exacerbates pathological signs
of hypoxic pulmonary hypertension. A neural microcircuitry consistent with an
axon reflex pathway is outlined histochemically. We conclude that endogenous CGRP
modulates pulmonary vascular tone in hypoxic pulmonary hypertension which
requires intact primary sensory fibers.
PMID- 9657353
TI - Effect of continuous infusion of vasopressin on glomerular growth response in
spontaneously hypertensive rats.
AB - Vasopressin (VP) is thought to play an important role in the pressor and
proliferative responses of renal glomeruli. We have utilized the spontaneously
hypertensive rat (SHR) model to determine if glomerular proliferation is induced
by chronic infusion of exogenous VP. SHR were continuously infused with 0.1
ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control
group) for fifteen days using osmotic minipumps, and the histological alterations
and level of expression of platelet-derived growth factor B-chain (PDGF-B) and
transforming growth factor (TGF)-beta1 mRNA were determined. We observed no
significant differences in systolic blood pressure, heart rate, serum
electrolytes, protein and creatinine among the three groups of rats, but urine
volume was found to be significantly decreased, and urine osmolality
significantly increased, in the H-VP group. Kidney weight was significantly
higher in the H-VP and L-VP groups than in the control group, and glomerular
diameter was higher in the H-VP group. When we measured mesangial injury score
and cellularity in the glomeruli of these animals, we observed VP dose-dependent
proliferative changes. In the immunofluorescence study, although we did not find
an obvious difference in depositions of collagen types III, IV and VI, alpha
smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF
beta1 increased in several glomeruli in the H-VP group. Reverse transcription
polymerase chain reaction (RT-PCR) revealed no significant differences in the
glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of
expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups
than in the control group. These findings suggest that VP may contribute to
glomerular proliferation, and that VP may exert its effects in part through the
induction of TGF-beta1 expression. These results also raise the possibility that
blockade of VP receptors may be useful in the treatment of some forms of
glomerular disease.
PMID- 9657354
TI - Sympathetic pathways mediate GLP-1 actions in the gastrointestinal tract of the
rat.
AB - The aim of this study was to establish the actions of GLP-1 (7-37) on
gastrointestinal motility in rats. We prepared anaesthetized Sprague-Dawley rats
with strain-gauges in the antrum, duodenum and the proximal jejunum and a
catheter in the aorta close to the coeliac artery for close infusion of
substances. Intraarterial GLP-1 infusions (3 x 10(-10) and 3 x 10(-9) moles/kg
per 10 min) (n = 8) induced inhibition of spontaneous motor activity in the
antrum, duodenum and proximal jejunum. Inhibition induced by GLP-1 was reversed
by i.v. infusion of GLP-1 receptor antagonist, Exendin (9-39) (3 x 10(-8)
moles/kg per 10 min) (n = 6). Neither the presence of L-NNA (10(-5) moles/kg) (n
= 9) nor the VIP receptor antagonist [4-Cl-D-Phe6, Leu17]-VIP (3 x 10(-8)
moles/kg per 10 min) (n = 8) modified responses to GLP-1. However, a combination
of the adrenergic blockers phentolamine and propranolol (1 mg/kg each) (n = 8)
completely blocked motor actions of GLP-1 in all the organs studied. Moreover,
inhibition of gastrointestinal motor activity by GLP-1 was blocked by previous
infusion of hexamethonium (10 mg/kg) (n = 4). This study demonstrates that GLP-1
inhibits gastrointestinal motor activity of the rat acting on specific GLP-1
receptors and via stimulation of adrenergic pathways.
PMID- 9657355
TI - Stimulation of ACTH and GH release by angiotensin II in normal men is mediated by
the AT1 receptor subtype.
AB - This study was performed in order to determine whether the stimulatory effect of
plasma angiotensin II (ANG II) on Adrenocorticotropic hormone (ACTH) and growth
hormone (GH) secretion in humans is mediated by AT1 subtype receptors. For this
purpose, the effects of the administration of the AT1 receptor antagonist,
losartan (50 mg p.o.) or a placebo on the ACTH and GH responses to ANG II (i.v.
infusion for 60 min of successively increasing doses (4, 8 and 16 ng/kg/min);
each dose for 20 min) were evaluated in eight normal men. ANG II infusion induced
significant increases in both serum ACTH and GH levels (mean peaks were 1.6- and
four-times higher than baseline, respectively). The ACTH response to ANG II was
completely abolished by pretreatment with losartan. Also, the ANG II-induced GH
rise was reduced by administration of losartan, but the GH response was still
significantly higher than the basal value (mean peak was twice as high as the
baseline). These data provide evidence of AT1 receptor involvement in mediation
of the ANG-II stimulating effect on ACTH and GH secretion.
PMID- 9657356
TI - Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and
hepatocellular carcinoma.
AB - Cholesterol is used by cells for biosynthetic processes and for steroid
synthesis. Although the role of cholesterol in tumorigenesis is not clear it is
known that steroids are important factors in human carcinogenesis. A polypeptide,
diazepam binding inhibitor (DBI), which is an endogenous ligand for peripheral
benzodiazepine receptors enhances steroidigenesis by promoting cholesterol
delivery to the inner mitochondrial membrane which represents the rate-limiting
step of steroid biosynthesis. We have assayed the total cholesterol (TC) and the
DBI plasma concentrations in patients with liver cirrhosis complicated by
hepatocellular carcinoma (HCC) in comparison with those of uncomplicated liver
cirrhosis. TC and DBI levels have been studied in 73 cirrhotic patients and in 23
patients with HCC. Both TC and DBI levels were higher in HCC patients when
compared with age, sex and Child-Pugh class matched cirrhotic controls. The
values (mean+/-S.D.) in patients in Child-Pugh class B and C with and without HCC
were respectively 128+/-30 mg/dl vs. 106+/-27 mg/dl (P < 0.01) and 2.05+/-0.78
pmol/ml vs. 0.78+/-0.84 pmol/ml (P < 0.0001). The data may be the result of the
metabolic influence of tumors that enhances steroid biosynthesis during tumor
proliferation.
PMID- 9657357
TI - Effects of long term treatment with corticotropin releasing factor on
corticotropic tumor cells in vitro.
AB - hCRF inhibits proliferation of corticotropic tumor cells cultivated in serum
reduced medium via interaction with CRF-receptors. This effect was attenuated by
the specific antagonist hCRF (9-41), but not by a variety of substances which are
inhibitors of cAMP production or cAMP-dependent kinases, suggesting that the
effect was not mediated via cAMP. The growth inhibiting effect of hCRH was
developed after 4 h incubation, a longer hCRF treatment did not change the effect
observed after 4 h. Simultaneously, after hCRF treatment for 4 days the cells
were insensitive for ACTH release by hCRF stimulation despite of an increase in
the number of secretory granules. The results show that the inhibition of
proliferation of pituitary tumor cells by hCRF seems to be a rapid receptor
mediated process connected with morphological changes, but not mediated via
activation of adenylate cyclase.
PMID- 9657358
TI - Effect of bombesin at low doses on the secretion of the exocrine pancreas and on
plasma gastrin concentration in the conscious pig.
AB - We investigated the role of low-doses of bombesin in the regulation of exocrine
secretion in the pancreas of the conscious pig. In ten growing castrated male
Large White pigs, bombesin was infused intravenously for 1 h at doses of 0 to 500
pmol/kg/h under a stimulation of secretin (36 pmol/kg/h). In six pigs, bombesin
(50 pmol/kg/h) was administered alone for 2 h and its effect on pancreatic
secretion was compared to that of an infusion of secretin. The pancreatic juice
and the blood were collected at 15-min intervals for use in assays of protein in
the juice and gastrin in the plasma. When bombesin was infused alone or in
combination with secretin, the volume secreted was not altered. The protein
output was not altered by secretin, but was increased by the infusion of
bombesin, in a dose-dependent manner, reaching a plateau at 250 pmol/kg/h. The
plasma gastrin levels were increased by bombesin, starting with the 50 pmol/kg/h
dose. This effect was maximal at a dose of 100 pmol/kg/h. The levels remained
below those measured after a standard meal, demonstrating that the effect of
bombesin on the studied parameters is of physiological significance.
PMID- 9657359
TI - Receptor mechanisms of bradykinin-mediated activation of prenodal lymphatic
smooth muscle.
AB - We have previously shown that several endogenous vasoactive agents constrict
prenodal lymph vessels in the canine forelimb. In this study, we assessed the
receptor mechanisms by which bradykinin activates lymphatic smooth muscle.
Intralymphatic (i.l.) infusion of bradykinin at concentrations of 3.82 x 10(-6),
3.82 x 10(-5) and 3.82 x 10(-4) molar significantly increased lymphatic perfusion
pressure. To determine the potential role of lymphatic alpha-receptors in this
response, we infused bradykinin at a concentration of 3.82 x 10(-4) molar i.l.
before and during intra-arterial (i.a.) phentolamine administration. Prior to
phentolamine, bradykinin resulted in a doubling of the lymphatic perfusion
pressure. Phentolamine alone had no effect on the resting lymphatic pressure, but
significantly reduced forelimb arterial pressures. When the infusion of
bradykinin was repeated during phentolamine administration, there was no
significant change in the lymphatic perfusion pressure. To determine the subclass
of alpha-adrenergic receptors involved in this response, we infused bradykinin
and the alpha1-receptor agonist phenylephrine i.l. before and during
administration of i.a. prazosin, a specific alpha1-receptor antagonist, i.a.
Prior to prazosin, both phenylephrine and bradykinin significantly increased
lymphatic perfusion pressure. During prazosin administration, neither
phenylephrine nor bradykinin significantly altered the lymphatic perfusion
pressure. These data indicate that bradykinin-mediated increases in prenodal
lymphatic smooth muscle tone are mediated by lymphatic alpha1-adrenergic
receptors.
PMID- 9657360
TI - Inhibition of gastric acid secretion by galanin in rats. Relation to endogenous
histamine release.
AB - Inhibitory effect of galanin on basal and secretagogs-stimulated gastric acid
secretion was investigated in urethane-anesthetized rats. A rat stomach was
mounted in an ex-vivo chamber, perfused with saline, and either gastric acid or
alkaline secretion was determined by titrating the perfusate. Gastric mucosal
blood flow (GMBF) was measured by a laser Doppler flowmeter. Intravenous infusion
of galanin dose-dependently inhibited the increase of acid secretion induced by
pentagastrin and carbachol but not by histamine, without any influence on the
GMBF response. Galanin also reduced basal acid secretion while increasing GMBF,
but did not evoke any change in basal gastric alkaline secretion. M15, which is a
galanin receptor antagonist in the central nervous system but acts as a full
agonist in the gastrointestinal smooth muscle, also suppressed pentagastrin
induced acid secretion, similar to galanin. In addition, pentagastrin increased
the release of histamine into the gastric lumen, and this response was
significantly inhibited by galanin. These results suggest that the inhibitory
effect of galanin on acid secretion is mediated by suppression of endogenous
histamine release from enterochromaffin-like cells and that the process may be
related to the activation of the same subtype of galanin receptors as in the
central nervous system and pancreatic beta-cells.
PMID- 9657361
TI - An aminoisobutyric acid-containing analogue of the cockroach tachykinin-related
peptide, LemTRP-1, with potent bioactivity and resistance to an insect
angiotensin-converting enzyme.
AB - Nine tachykinin-related peptides (TRPs), designated LemTRP-1-9, were recently
isolated from the cockroach, Leucopheae maderae. To obtain a LemTRP resistant to
endo- and exoprotease-mediated hydrolysis, we synthesized a peptide with one of
the carboxy terminus residues substituted for a sterically hindered
aminoisobutyric acid (Aib) and with the amino terminus blocked with a
pyroglutamate. The Aib-containing analogue of the nonapeptide LemTRP-1 (Aib
LemTRP-1) thus has the sequence pGlu-Ala-Pro-Ser-Gly-Phe-Leu-Aib-Val-Arg-NH2.
This analogue was shown to be resistant to hydrolysis by recombinant angiotensin
converting enzyme (ACE), from Drosophila melanogaster. Endogenous LemTRP-1 on the
other hand was rapidly hydrolysed by ACE at the Gly7-Val8 bond, resulting in a
single heptapeptide. The Aib-LemTRP-1 has about the same potency as LemTRP-I in
inducing contractions of the L. maderae hindgut muscle. It was also tested in
intracellular recordings for ability to induce firing of action potentials in
dorsal unpaired median (DUM) neurons in the metathoracic ganglion of the locust
Locusta migratoria. The Aib-containing analogue was nearly as active as LemTRP-1
and the natural ligand locustatachykinin I. LemTRP-1 and Aib-LemTRP-1 had the
same transient time course of action on the cockroach hindgut. This suggests that
peptide degradation is not likely to be the cause of the transient action of
TRPs.
PMID- 9657362
TI - Fat metabolism during exercise: a review. Part I: fatty acid mobilization and
muscle metabolism.
AB - This is the first part in a series of three articles about fat metabolism during
exercise. In this part the mobilization of fatty acids and their metabolism will
be discussed as well as the possible limiting steps of fat oxidation. It is known
for a long time that fatty acids are an important fuel for contracting muscle.
After lipolysis, fatty acids from adipose tissue have to be transported through
the blood to the muscle. Fatty acids derived from circulating TG may also be used
as a fuel but are believed to be less important during exercise. In the muscle
the IMTG stores may also provide fatty acids for oxidation after stimulation of
hormone sensitive lipase. In the muscle cell, fatty acids will be transported by
carrier proteins (FABP), and after activation, fatty acyl CoA have to cross the
mitochondrial membrane through the carnitine palmytoyl transferase system, after
which the acyl CoA will be degraded to acetyl CoA for oxidation. The two steps
that are most likely to limit fat oxidation are fatty acid mobilization from
adipose tissue and transport of fatty acids into the mitochondria along with
mitochondrial density and the muscles capacity to oxidize fatty acids.
PMID- 9657363
TI - Detraining effects on bone mass in young male rats.
AB - The effects of exercise training and detraining on bone mass were assessed in
young male Wistar rats. The rats were divided randomly into sedentary control (C)
and exercise training (T) groups. The T rats were trained for 10 weeks followed
by a 10-week detraining period. Training consisted of running exercise on a
rodent treadmill at 35 m/min, +5-degree inclination, 60 min/day, 5 days/week.
Training induced significant gain in fat-free dry weight and length of bones
(femur, tibia, humerus and coxa) and bone mineral content (femur, tibia and
humerus). Histological analysis at the tibial mid-shaft revealed a significant
increase in total and cortical areas without a significant change in marrow area
in the T group. Bone mass acquired through running exercise was retained for 10
weeks after cessation of training. These results indicate that running exercise
leads to increased cortical bone associated with enhanced periosteal bone
formation which is also maintained even after stopping exercise training, and
suggest that training effects on the skeleton in bone mass level do not diminish
immediately after cessation of training.
PMID- 9657364
TI - Endurance training and its effect upon the activity of the GH-IGFs system in the
elderly.
AB - There is an age-associated decline in the activity of the GH-IGFs system.
However, so far, it has not been studied, whether this decline in somatotrophic
activity might be preventable by intensive exercising. We studied 11 elderly male
(50-78 years) marathon runners and 10 age-matched male (52-73 years) sedentary
controls to evaluate plasma concentrations of GH, total and free IGF-I and IGF-II
and of IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3 and insulin. When
comparing the two groups (runners vs controls) no differences were found in GH
(1.0 +/- 1.2 vs 1.3 +/- 1.3 microg/l [mean +/- SD]), IGF-1 (115 +/- 23 vs 113 +/-
21 microg/l), IGF-II (961 +/- 192 vs 864 +/- 125 microg/l), free IGF-1 (227 +/-
80 vs 318 +/- 146 ng/l), free IGF-II (563 +/- 249 vs 492 +/- 108 ng/l), IGFBP-3
(2403 +/- 515 vs 2307 +/- 326 microg/l) or insulin (26 +/- 13 vs 27 +/- 18 mU/l).
However, IGFBP-1 (4.44 +/- 2.61 vs 2.28 +/- 0.93 microg/l) and IGFBP-2 (493 +/-
143 vs 340 +/- 186 microg/l) were found to be significantly increased in marathon
runners. In conclusion, our findings do not support the hypothesis that the age
associated decline in GH, IGF-1 and IGFBP-3 may be preventable by intensive
endurance training. However, marathon running affects the regulation of the GH
IGFs system activity at the level of IGFBP-1 and -BP-2.
PMID- 9657365
TI - Visual and brainstem auditory evoked potentials and maximal aerobic exercise:
does the influence of exercise persist after body temperature recovery?
AB - Transversal studies have shown a strong correlation between specific evoked
potential (EP) values and specific physical activities, as well as between EP
values and the amount of training. Prior to longitudinal studies investigating
the effect of training in EPs, it is mandatory to determine whether a recent
training session could interfere with regular EP recording. Exercise-induced
hyperthermia is known to modify EP values. The purpose of the study was to
determine whether an acute exercise can induce EP modification persisting after
body temperature recovery. We measured two sets of visual evoked potentials
(VEPs) and brainstem auditory evoked potentials (BAEPs) in 16 males (8 cyclists
and 8 sedentary peers), one before and the other after a maximal cycloergometric
graded exercise test. The second test was performed immediately after body
temperature recovery. We chose to test cyclists, as their specific training
corresponded to the exercise test we performed on a cycloergometer. The repeated
measures before and after the exercise test showed no significant differences,
neither in VEPs nor in BAEPs, for any subject of the study. Recording VEPs and
BAEPs in cyclists, we observed no difference related to this particular sport
training. This study showed that VEP and BAEP values were similar to those
measured before a maximal exercise when body temperature returned to pre-exercise
value. This original work demonstrated that VEP and BAEP recordings can be
reliably performed after a recent training session, provided body temperature has
returned to basal level.
PMID- 9657366
TI - Endurance training in females: changes in beta-endorphin and ACTH.
AB - Previous results from endurance training in women have been discrepant in regard
to influences on basal and maximum adrenocorticotropin (ACTH) and beta-endorphin
(beta-EP) concentrations before and after exhaustive exercise. A group of 23
untrained young women ran 3 times a week for 30 min at an individual specific
intensity corresponding to their respective anaerobic threshold, derived from the
lactate performance curve obtained from prior treadmill testing. ACTH and beta-EP
were measured at rest, as well as 5 and 30 min after exhaustive progressive
spiroergometric treadmill running, both before and after the 8 week endurance
training program. Basal beta-EP did not change after training, but less elevated
concentrations were measured both 5 (p < 0.05) and 30 min (p < 0.05) after
exercise, after the training program. In contrast, the resting concentration of
ACTH increased significantly; the respective maximum concentration was less
elevated after 5 min and much less elevated 30 min after the exercise (p < 0.05).
Positive correlations were found after the exhaustive exercise between beta-EP
and ACTH, as well as between maximum lactate and ACTH. Training was associated
with significant changes in maximum running speed (p < 0.01), maximum oxygen
uptake (p < 0.01) and the running speed at the anaerobic threshold (p < 0.05).
Maximum lactate and the level of perceived exertion remained unchanged, showing a
similar level of exhaustion. Our results indicate that endurance training
modulates the hormonal responses of beta-EP and ACTH to comparable workloads of
high intensity. After the training program the maximum concentrations are
significantly lower during the recovery period. The tendency to elevated basal
ACTH, and thus elevated cortisol, might be a new factor to consider in evaluation
of endurance training induced hormonal disturbances in women.
PMID- 9657367
TI - Comparison of muscle cross-sectional areas between weight lifters and wrestlers.
AB - The purpose of this study was to investigate the difference in the magnitude of
muscular development between Olympic weight lifters and wrestlers through the
measurements of fat-free mass (FFM) and limb muscle cross-sectional area (CSA).
Subjects were college Olympic weight lifters (N = 34, age = 20.0 +/- 1.3 years,
stature = 1.67 +/- 0.07 m, body mass = 70.1 +/- 10.2 kg, X +/- SD) and wrestlers
(N = 33,20.3 +/- 1.2 years, 1.69 +/- 0.06 m, 71.0 +/- 1.8 kg) who had identical
range of body mass. Body density and the CSAs of reciprocal muscle groups in the
forearm, upper arm, lower leg and thigh were measured by underwater weighing and
B-mode ultrasound methods, respectively. No significant difference was found in
body density between the weight lifters (1.077 +/- 0.007 g x ml(-3)) and
wrestlers (1.076 +/- 0.008 g x ml(-3)). Moreover, FFM and the CSA values of all
muscle groups tested were similar in the two groups of weight-classified
athletes, with an exception that the wrist flexor CSA was significantly larger in
wrestlers than in weight lifters, and the knee extensor and thigh (extensors +
flexors) CSAs were larger in weight lifters than in wrestlers. The total muscle
CSA of every site was significantly correlated to FFM2/3 in the separate groups;
r = 0.714 to 0.815 (p < 0.05) in weight lifters and r = 0.769 to 0.919 (p < 0.05)
in wrestlers. While the CSA-to-FFM2/3 ratios of the upper arm and wrist flexor
muscles were significantly higher in wrestlers than in weight lifters, those of
the thigh and knee extensor muscles were higher in weight lifters than in
wrestlers. Thus, the present results suggest that an event-related difference
exists in the magnitude of limb muscle CSA between competitive weight lifters and
wrestlers of similar FFM.
PMID- 9657368
TI - Effect of recovery duration on the force-velocity relationship.
AB - The aim of this study was to investigate the effect of different Recovery
Duration (RD) between each sprint (30 s, 1 min, 3 min, 5 min, 10 min and 24 h)
during the force-velocity test and to analyse associated anaerobic parameters
such as maximal anaerobic power and blood lactate concentrations. Twelve male
physical education students aged from 18 to 26 years took part in this study.
Maximal anaerobic power (Pmax) was not statistically different whatever the
recovery duration (from 885 to 938 watts, for RD 30 s to RD 24 h, respectively).
This was associated with a tendency during the longer RD tests for optimal
velocity to decrease (p = ns) while optimal force increased (p < 0.05). Blood
lactate concentrations were regularly increased from 1.7 to a 9 mmol x l(-1)
plateau at sprint 4 for RD tests < 10 min and were quite stable from the second
sprint with an associated value from 2.2 to 4.7 mmol x l(-1) for RD 10 min and RD
24 h. In spite of statistically different values for [L]s between the tests, the
power developed for each sprint remained unchanged. These data indicate that the
attainment of maximal power seems independent from the recovery duration (> 10 s)
and the pre-blood lactate values observed between each sprint during the force
velocity test. The way to reach Pmax was different between the tests. Different
partition of energetic pathways are suggested. In conclusion, the force-velocity
test could be performed with a shorter and the arbitrary five minutes recovery
duration.
PMID- 9657369
TI - Aerobic and anaerobic energy expenditure during exhaustive ramp exercise.
AB - Ramp tests are often manipulated so that oxygen uptake is able to interpret
energy expenditure in its entirety. We hypothesized that oxygen deficits during
ramp exercise to exhaustion would be significant, providing a more complete
description of the types of energy expenditure available for this mode of
testing. Oxygen deficits were obtained during a slow ramp (681 +/- 71 s) and a
fast ramp (275 +/- 33 s) to exhaustion. Twelve healthy men (age 35 +/- 3 yrs;
VO2max 51 +/- 10 ml x kg(-1) x min(-1)) performed several 10 min submaximal bike
rides (at or below ventilatory threshold) to determine work rate -O2 uptake
demands. Estimated O2 demands were compared to measured O2 uptake during each
ramp test, the difference representing an oxygen deficit. Work levels were
controlled and measurements collected with a commercially available electrically
braked bike ergometer and metabolic testing system (MedGraphics, Minn., MN). Data
were collected and averaged in 30 s time periods, power in watts (W), energy
expenditure in cumulative O2 (L). Using a paired t-test, cumulative O2 uptakes
were significantly lower (p = 0.0001) when measured O2 uptakes (26.0 L +/- 4.5
for slow ramp; 10.8 L +/- 2.8 for fast ramp) were compared to estimated O2
demands (29.0 L +/- 3.7 for slow ramp; 14.1 L +/- 3.5 for fast ramp). Anaerobic
energy expenditures (oxygen deficits) represented 10.8% and 23.4% of total energy
expenditure for slow ramps and fast ramps, respectively. Comparisons of the
slopes for each test condition revealed significant differences (steady state >
slow ramp > fast ramp; p = 0.0001,ANOVA). We conclude that the oxygen deficit
during ramp testing represents a significant part of total energy expenditure.
PMID- 9657370
TI - Erythropoietin (rHuEPO) doping: effects of exercise on anaerobic metabolism in
rats.
AB - The purpose of this study was to investigate the effects of recombinant human
erythropoietin (rHuEPO) administration on energy metabolism during exercise.
Specifically, the contribution of anaerobic (glycogen) metabolism during exercise
was evaluated. Sprague-Dawley rats were randomly assigned to an experimental
[rHuEPO] (600 U x kg(-1) of Eprex, every 3 days) or control (equivalent volume of
saline) group. After 15 days of treatment, animals from both groups were randomly
subjected to either a 30-minute exercise (swimming with 5% body weight added) or
resting period. They were sacrificed at the end of the exercise period. Their
liver and muscles were quickly removed and frozen in liquid nitrogen. Blood was
also sampled. rHuEPO administration resulted in a significant (P < 0.05) increase
of hematocrit (from 42 +/- 2 to 54 +/- 7 L/L). In the rHuEPO group, both muscle
glycogen and free fatty acids were higher whereas lactate was lower at the
conclusion of the exercise period (P < 0.05). These results suggest that energy
substrate utilization during exercise is affected by enhanced oxygen
availability. Finally, a lower overall contribution to energy production from
anaerobic metabolism during exercise followed rHuEPO administration.
PMID- 9657371
TI - Detection of human chorionic gonadotrophin misuse in sports.
AB - The peptide hormone human chorionic gonadotrophin (hCG) was measured in the urine
of 5663 male athletes collected for doping analysis in Flanders during the period
1993-1996. Using the Abbott IMx hCG procedure, the free and whole molecule
associated beta-subunit of human chorionic gonadotrophin was determined.
Statistical evaluation of the data results in a far outside value of 2.28 mIU/ml.
The decision limit, i.e. the concentration at which a sportsman will be
considered positive, is set at 5 mIU/ml to ensure with the greatest possible
degree of certainty that no false positive results are reported.
PMID- 9657372
TI - Mode of receptor binding and activation by plasminogen-related growth factors.
AB - Hepatocyte growth factor/scatter factor (HGF/SF) and macrophage stimulating
protein (MSP) are plasminogen-related kringle proteins that lost serine protease
domain enzymatic activity and became ligands for cell surface tyrosine kinase
receptors. They are activated by cleavage to disulfide-linked alphabeta chains.
Surprisingly, despite structural similarities, the high affinity receptor binding
regions of the two proteins are different: alpha chain for HGF, and beta chain
for MSP. We propose that after cleavage exposes a beta chain binding site (high
affinity for MSP, low affinity for HGF), monomeric ligand induces receptor
dimerization and activation via alpha and beta chain binding sites of different
affinity.
PMID- 9657373
TI - Secondary structure of some elements of 18S rRNA suggests that strongylid and a
part of rhabditid nematodes are monophyletic.
AB - Analysis of the secondary structure of 18S rRNA molecules in nematodes revealed
some new traits in the secondary structure peculiar to their hairpin 17. Some of
them are characteristic of all the nematodes, whereas others are characteristic
exclusively of the order Rhabditida. The loss of a nucleotide pair in the highly
conservative region of hairpin 17 distinguishes 18S rRNA of the Strongylida and
some species of the Rhabditida from other nematodes and, moreover, from all other
organisms. Hence, it is possible to regard the Strongylida and a part of the
Rhabditida including Caenorhabditis elegans as a new monophyletic taxon.
PMID- 9657374
TI - An NMR-based identification of peptide fragments mimicking the interactions of
the cathepsin B propeptide.
AB - Selected fragments of the 62-residue proregion (or residues 1p-62p) of the
cysteine protease cathepsin B were synthesized and their interactions with
cathepsin B studied by use of proton NMR spectroscopy. Peptide fragments 16p-51p
and 26p-51p exhibited differential perturbations of their proton resonances in
the presence of cathepsin B. These resonance perturbations were lost for the
further truncated 36p-51p fragment, but remained in the 26p-43p and 28p-43p
peptide fragments. Residues 23p-26p or TWQ25A in the N-terminal 1p-29p fragment
did not show cathepsin B-induced resonance perturbations although the same
residues had strongly perturbed proton resonances within the 16p-51p peptide.
Both the 1p-29p and 36p-51p fragments lack a common set of hydrophobic residues
30p-35p or F30YNVDI35 from the proregion. The presence of residues F30YNVDI35
appears to confer a conformational preference in peptide fragments 16p-51p, 26p
51p, 28p-43p and 26p-43p, but the same residues induce the aggregation of
peptides 16p-36p and 1p-36p. The peptide fragment 26p-43p binds to the active
site, as indicated by its inhibition of the catalytic activity of cathepsin B.
The cathepsin B prosegment can therefore be reduced into smaller, but functional
subunits 28p-43p or 26p-43p that retain specific binding interactions with
cathepsin B. These results also suggest that residues F30YNVDI35 may constitute
an essential element for the selective inhibition of cathepsin B by the full
length cathepsin B proregion.
PMID- 9657375
TI - Overexpression of hMTH1 mRNA: a molecular marker of oxidative stress in lung
cancer cells.
AB - Human MutT homologue (hMTH1) mRNA was overexpressed in SV-40-transformed non
tumorigenic human bronchial epithelial cells (BEAS-2B cells) and in 11 out of 12
human lung cancer cell lines relative to normal human bronchial epithelial cells.
Expression levels of hMTH1 mRNA were inversely proportional to cellular levels of
8-oxo-deoxyguanosine. Together, these results suggest that hMTH1 gene expression
may represent a molecular marker of oxidative stress that could ultimately be
used to elucidate the temporal relationships between oxidative stress, genomic
instability and the development of lung cancer.
PMID- 9657376
TI - Structural and dynamic helix geometry alterations induced by mismatch base pairs
in double-helical RNA.
AB - A ribooligonucleotide microhelix derived from the acceptor stem of Escherichia
coli tRNA(Ala) having a C3-A70 mismatch in place of the G3-U70 wobble pair in the
wild-type tRNA(Ala), and a sequence variant with a regular U3-A70 base pair have
been investigated by NMR. In vivo, suppressor tRNA(Ala) variants with C3-A70 (as
well as several other) mismatch pairs are substrates for alanyl-tRNA synthetase
(ARS), supporting the hypothesis of an 'indirect' recognition of the identity
element 3-70 mismatch pair via structural modifications caused by the mispair in
comparison to canonical A-RNA helices. It is demonstrated that the C-A mismatch
likewise induces helix geometry alterations, in particular with respect to base
stacking in the vicinity of the mismatch. However, with reference to the 'wild
type' G3-U70 microhelix, destacking in the C3-A70 acceptor stem duplex occurs in
the opposite direction from the mismatch pair. Therefore it is concluded that the
locally enhanced conformational flexibility or dynamics associated with the
structural changes induced by the mismatch pairs could be an essential
prerequisite for optimal adaptation of the tRNA(Ala) acceptor stem to the contact
region of the ARS.
PMID- 9657377
TI - The carboxy-terminal domain of the receptor-associated protein binds to the
Vps10p domain of sortilin.
AB - Binding of the receptor-associated protein (RAP) to the newly identified putative
sorting receptor, sortilin, was analyzed by surface plasmon resonance analysis of
recombinant RAP and sortilin domains and compared with binding to megalin and low
density lipoprotein receptor-related protein (LRP). The data show that the RAP
binding site in sortilin is localized in the cysteine-rich lumenal part
homologous to yeast vacuolar protein-sorting 10 protein (Vps10p), and the
sortilin-binding site in RAP is localized in the carboxy-terminal domain III of
the three homologous domains in RAP. Whereas sortilin bound only RAP domain III,
megalin and LRP bound all RAP domains with the functional affinity order: domain
III >domain I > domain II.
PMID- 9657378
TI - Total chemical synthesis of bovine pancreatic trypsin inhibitor by native
chemical ligation.
AB - Bovine pancreatic trypsin inhibitor (BPTI) is an important model for the study of
protein folding. Herein we describe a robust approach to the total chemical
synthesis of BPTI using native chemical ligation of unprotected peptide segments
in aqueous solution. After refolding and oxidative formation of disulfides, the
target protein was purified by affinity chromatography. The synthetic BPTI was
characterized by mass spectrometry, inhibition assay, thermal denaturation and 2D
NMR spectroscopy, and was shown to be structurally and functionally identical to
natural BPTI. The synthetic strategy presented in this paper has enabled us to
establish rapid access to novel analogues of BPTI.
PMID- 9657379
TI - Identification of a structural requirement for thyroid Na+/I- symporter (NIS)
function from analysis of a mutation that causes human congenital hypothyroidism.
AB - Patients with congenital lack of I transport do not accumulate I in their
thyroids, often resulting in severe hypothyroidism. A single amino acid
substitution in the thyroid Na+/I- symporter (NIS), proline replacing threonine
at position 354 (T354P), was recently identified as the cause of this condition
in two independent patients. Here we report that the lack of I- transport
activity in T354P NIS generated by site-directed mutagenesis, is not due to a
structural change induced by proline, but rather to the absence of a hydroxyl
group at the beta-carbon of the amino acid residue at position 354. Hence, this
hydroxyl group is essential for NIS function.
PMID- 9657380
TI - A new opioid peptide predicted from cloned cDNAs from skin of Pachymedusa
dacnicolor and Agalychnis annae.
AB - We have isolated a cDNA encoding a precursor of dermorphin from the skin of
Pachymedusa dacnicolor. Besides four copies of this opioid peptide, the deduced
sequence also contains the genetic information for a novel peptide Tyr-Ile-Phe
His-Leu-Met-Asp-NH2. This differs from Met-deltorphin by the presence of Ile at
position 2. In a related precursor from the skin of Agalychnis annae, the
sequence of this peptide is in the 3'-untranslated region of the cloned cDNA.
From earlier results we predict that in skin peptides the second residue is D
allo-Ile. We have synthesized this and related peptides with different D-amino
acids, and determined their delta agonist activity. The peptide with D-nor-Leu
binds with high affinity to delta receptors, while that with D-allo-Ile is about
100 times less active.
PMID- 9657381
TI - A calcium pump at the higher plant nuclear envelope?
AB - Evidence for a Ca2+-pump at the nuclear envelope (NE) in plant cells has been
obtained using confocal and electron microscope immunocytochemistry and
antibodies raised to a plant homologue of the mammalian SERCA pump. This is the
first evidence suggesting an NE Ca2+-pump in plants. In addition to being
localised with the NE in interphase, the antigen was localised to membrane
derived from the NE and associated ER during mitosis, correlating with known Ca2+
pools. The work suggests that a SERCA pump is present at the NE of plant as well
as animal cells.
PMID- 9657382
TI - On the origin of the '35-mus kinetics' of P680(+.) reduction in photosystem II
with an intact water oxidising complex.
AB - The origin of the '35-micros kinetics' of P680(+.) reduction in photosystem II
(PS II) with an intact water oxidising complex has been analysed by comparative
measurements of laser flash induced changes of the 830-nm absorption and the
relative quantum yield of chlorophyll (Chl) fluorescence. The latter parameter
was monitored at a time resolution of 500 ns by using newly developed home built
equipment [Reifarth, F., Christen, G. and Renger, G. (1997) Photosynth. Res. 51,
231-2421. It was found that: (i) the amplitudes of the unresolved ns-kinetics of
both 830-nm absorption changes and the rise of fluorescence yield exhibit
virtually the same period four oscillation pattern when dark adapted samples are
excited with a train of saturating laser flashes; (ii) the corresponding
oscillation patterns of the normalised extent of the 35-micros kinetics under
identical excitation conditions are strikingly different with maxima after the
3rd and 5th flash for the 830-nm absorption changes vs. pronounced maxima after
the 4th and 8th flash for the rise of the fluorescence yield. The period four
oscillations unambiguously show that the '35-micros kinetics' of P680(+.)
reduction are characteristic for reactions in PS II entities with an intact water
oxidising complex. However, the disparity of the oscillation patterns of (ii)
indicates that in contrast to the ns components of P680(+.) reduction the 35
micros kinetics do not reflect exclusively an electron transfer from Y(Z) to
P680(+.). It is inferred that a more complex reaction takes place which comprises
at least two processes: (a) P680(+.) reduction by Y(Z) and (b) coupled and/or
competing reaction(s) which give rise to additional changes of the chlorophyll
fluorescence yield.
PMID- 9657383
TI - Cloning and characterization of the gene encoding the human peroxisomal assembly
protein Pex3p.
AB - Proteins essential for the assembly of functional peroxisomes are designated
peroxins and are encoded by PEX genes. In yeast, Pex3p was previously identified
as a peroxisomal integral membrane protein indispensable for peroxisome
biogenesis and integrity. Here we report the cloning of the orthologous human
PEX3 gene. It encodes a polypeptide of 373 amino acids (42 kDa) and is expressed
in all tissues examined. As shown by transfection of epitope tagged constructs
and immunofluorescence analysis, human Pex3p is localized at the peroxisome. The
N-terminal 40 amino acids were revealed to be sufficient to target a GFP reporter
protein to the peroxisome. A positively charged five amino acid sequence within
this N-terminal region is highly conserved from yeast to human Pex3p.
Overexpression of human Pex3p leads to proliferation of ER membranes in COS7
cells. Since disruption of human peroxins has been shown to result in peroxisomal
biogenesis disorders, PEX3 is another candidate gene being involved in this
disease group.
PMID- 9657384
TI - Structure and mRNA expression of a bovine trp homologue related to mammalian trp2
transcripts.
AB - Mammalian homologues of the transient receptor potential (trp) gene product from
Drosophila melanogaster function as Ca2+-selective or non-selective cation
channels. Complementary DNA was isolated from a bovine testis cDNA library which
encodes bovine trp2 (btrp2), a protein of 432 amino acid residues comprising four
predicted transmembrane segments. Btrp2 mRNA is expressed in bovine testis,
spleen and liver but not in brain, heart, adrenal gland or retina. In bovine
testis expression of btrp2 mRNA is restricted to spermatocytes but is not present
in spermatogonia, Leydig or Sertoli cells suggesting that btrp2 may contribute to
the formation of ion channels in sperm cells.
PMID- 9657385
TI - Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand
expression in microglial cells.
AB - Apoptosis plays an important role in neurodegeneration, although the mechanisms
and mediators in the brain are largely unknown. Because microglial cells have
been suggested to contribute to apoptosis in neurological disorders, we
investigated the expression of the death ligand CD95L in this cell type. We found
that, compared to classical mediators of microglial activation, the most potent
inducer of CD95L was oxidative stress. Exposure of microglial cells to H2O2 or
paraquat rapidly triggered CD95L mRNA and protein expression, associated with the
activation of transcription factor NF-kappaB. Enhanced expression of CD95L was
further found following exposure of cells to hypoxia and subsequent
reoxygenation. Our results indicate a potential role of CD95L in oxidative stress
mediated cell death, ischemia/reperfusion and other diseases with a disturbed
redox balance.
PMID- 9657386
TI - Substrate-dependent activation requirements and kinetic properties of protein
kinase C.
AB - Protein kinase C (PKC) requires basic amino acids around the phosphorylated Ser
or Thr. Previous studies of the effector requirements of PKCs alpha, beta and
gamma with two commonly used substrates, MBP3-14 (AQKRPSQRSKYL) and peptide
epsilon (ERMRPRKRQGSVRRRV), revealed that MBP3-14 phosphorylation required Ca2+,
phosphatidylserine and diacylglycerol, while peptide epsilon supported high
levels of phosphatidylserine-dependent activity in the absence of Ca2+ or
diacylglycerol. Since the Arg versus Lys content is much larger in peptide
epsilon than in MBP3-14, we examined the role of these amino acids in conferring
substrate-dependent effector requirements for PKC activation. We substituted Lys
for Arg in peptide epsilon (peptide epsilon[R-->K]) and Arg for Lys in MBP3-14
(MBP3-14[K-->R]) and analyzed the effector requirements and kinetic properties of
PKCs alpha, beta and gamma with the parent and modified peptides. In general,
significant Ca2+ and diacylglycerol dependence was observed with peptide
epsilon[R-->K] as compared to peptide epsilon. On the other hand, the effector
requirements with MBP3-14[K-->R] were the same as with MBP3-14, presumably due to
a subthreshold Arg content. Both Km and Vmax determined in the presence of Ca2+,
phosphatidylserine and diacylglycerol were increased by the peptide epsilon
modification for all three isoenzymes, while the only effect of MBP3-14
modification was a decrease in Km for PKCbeta. Km and Vmax values for peptide
epsilon and peptide epsilon[R-->K] phosphorylation by PKCalpha were also
determined in the absence of Ca2+ or diacylglycerol. While diacylglycerol had no
effect, Ca2+ decreased the Km for both substrates to a similar extent. Overall,
the degree of effector dependence did not correlate with absolute Km values. The
mechanism of PKC activation by Arg-rich substrates, therefore, does not involve
their ability to bind to the active site.
PMID- 9657387
TI - Structural stabilization of botulinum neurotoxins by tyrosine phosphorylation.
AB - Tyrosine phosphorylation of botulinum neurotoxins augments their proteolytic
activity and thermal stability, suggesting a substantial modification of the
global protein conformation. We used Fourier-transform infrared (FTIR)
spectroscopy to study changes of secondary structure and thermostability of
tyrosine phosphorylated botulinum neurotoxins A (BoNT A) and E (BoNT E). Changes
in the conformationally-sensitive amide I band upon phosphorylation indicated an
increase of the alpha-helical content with a concomitant decrease of less ordered
structures such as turns and random coils, and without changes in beta-sheet
content. These changes in secondary structure were accompanied by an increase in
the residual amide II absorbance band remaining upon H-D exchange, consistent
with a tighter packing of the phosphorylated proteins. FTIR and differential
scanning calorimetry (DSC) analyses of the denaturation process show that
phosphorylated neurotoxins denature at temperatures higher than those required by
non-phosphorylated species. These findings indicate that tyrosine phosphorylation
induced a transition to higher order and that the more compact structure
presumably imparts to the phosphorylated neurotoxins the higher catalytic
activity and thermostability.
PMID- 9657388
TI - The mating factor response pathway regulates transcription of TEC1, a gene
involved in pseudohyphal differentiation of Saccharomyces cerevisiae.
AB - The transcription factor Tec1 is involved in pseudohyphal differentiation and
agar-invasive growth of Saccharomyces cerevisiae cells. The sole element in the
TEC1 promoter that has thus far been shown to control Tec1 function is the
filament response element. We find that the TEC1 promoter also contains several
pheromone response element sequences which are likely to be functional: TEC1
transcription is induced by mating factor, cell cycle regulated and dependent on
the Ste4, Ste18 and Ste5 components of the mating factor signal transduction
pathway. Using alleles of the transcription factor Ste12 that are defective in
DNA binding, transcriptional induction or cooperativity with other transcription
factors, we find little correlation between TEC1 transcript levels and agar
invasive growth.
PMID- 9657389
TI - Adhesion-related glycocalyx study: quantitative approach with imaging-spectrum in
the energy filtering transmission electron microscope (EFTEM).
AB - Large polysaccharide molecules composing the glycocalyx have been shown to
prevent cell adhesion. However, this process was not observed microscopically.
Terbium labeling, combined with a new quantitative imaging method based on
electron energy loss spectroscopy, allowed specific glycocalyx staining with
excellent contrast. Image analysis enabled us to compare glycocalyx structure in
free membrane areas and contacts between monocytic cells and bound erythrocytes.
Apparent glycocalyx thickness, in contact areas, was half of the sum of
glycocalyx thicknesses in free areas without label density increase.
Ultrastructural immunogold localization of CD43 molecules, a major component of
glycocalyx, was also demonstrated to be excluded from contact areas during
adhesion. Thus, both approaches strongly suggest that some glycocalyx elements
must exit from contact to allow binding of adhesion molecules.
PMID- 9657390
TI - Binding of a native titin fragment to actin is regulated by PIP2.
AB - Titin is a giant protein which extends from Z-line to M-line in striated muscles.
We report here the purification of a 150-kDa titin fragment, obtained after V8
protease treatment of myofibrils. This polypeptide was located at the N1-line
level, in a titin part known to exhibit stiff properties correlated to an
association with actin. By solid or liquid phase binding assays and
cosedimentation, we have clearly demonstrated a direct, saturable and relative
high affinity binding of the native titin fragment to F-actin. The 150-kDa titin
fragment was also shown to accelerate actin polymerization. Furthermore, the
actin-titin interaction was found to be inhibited by phosphoinositides.
PMID- 9657391
TI - Intrahelical side chain interactions in alpha-helices: poor correlation between
energetics and frequency.
AB - Polypeptide sequences in proteins may increase their tendency to adopt helical
conformations in several ways. One is the recruiting of amino acid residues with
high helical propensity. Another is the appropriate distribution of residues
along the helix to establish stabilising side chain interactions. The first
strategy is known to be followed by natural proteins because amino acids with
high helical propensity are more frequent in alpha-helices. If proteins also
followed the second strategy, stabilising amino acid pairs should be more
frequent than others. To test this possibility we compared empirical energies of
side chain interactions in alpha-helices with statistical energies calculated
from a data base of proteins with low homology. We find some correlation between
the stability afforded by the pairs and their relative abundance in alpha-helices
but the realisation of energetic preferences into statistical preferences is very
low. This indicates that natural alpha-helices do not regularly use intrahelical
side chain interactions to increase their stability.
PMID- 9657392
TI - Recombinant expression, purification and characterization of Kch, a putative
Escherichia coli potassium channel protein.
AB - The Escherichia coli gene kch, similar in primary structure to eukaryotic voltage
gated potassium channels, was cloned and overexpressed in E. coli. The protein
was solubilized from the plasma membrane with dodecylmaltopyranoside,
lauryldimethylamine oxide or N-laurylsarcosine and was purified in milligram
amounts by imidazole elution from a nickel-chelate column. The molecular mass of
the purified protein in a number of detergents with 12 carbon atom chains
suggests that rKch forms primarily tetramers of the 50 kDa monomers. CD
spectroscopy of the purified protein indicates a significant alpha-helical
content that is preserved upon addition of SDS.
PMID- 9657393
TI - The cloning and developmental regulation of murine diacylglycerol kinase zeta.
AB - Diacylglycerol kinases (DGKs) regulate the key signaling intermediates
diacylglycerol (DAG) and phosphatidic acid (PA). We isolated cDNA clones of mouse
diacylglycerol kinase zeta (mDGKzeta) and found that it shares 88% identity at
the nucleic acid level and 95.5% identity at the amino acid level with human
DGKzeta (hDGKzeta). Murine DGKzeta protein rose gradually during embryonic
development, and was abundant in newborn and adult brains. By RNA whole-mount in
situ hybridization, mDGKzeta was shown to be expressed in spinal ganglia and limb
buds at low level in E11.5 embryos and at higher level in E12.5 embryos. In E13.5
embryos, DGKzeta mRNA was highly expressed in vibrissa follicles, in spinal
ganglia, and in the interdigital regions of the developing limbs. Northern
blotting showed that DGKzeta expression was limited to specific anatomical
regions of the brain. Thus, the expression of DGKzeta is regulated temporally and
spatially during mammalian development and correlates with the development of
sensory neurons and regions undergoing apoptosis.
PMID- 9657394
TI - The chloroplast Ndh complex mediates the dark reduction of the plastoquinone pool
in response to heat stress in tobacco leaves.
AB - We have examined the effects of heat stress on electron transfer in the thylakoid
membrane of an engineered plastid ndh deletion mutant, delta1, incapable of
performing the Ndh-mediated reduction of the plastoquinone pool in the
chloroplast. Upon heat stress in the dark, the rate of PSII-independent reduction
of PSI after subsequent illumination by far-red light is dramatically enhanced in
both delta1 and a wild-type control plant (WT). In contrast, in the dark, only
the WT shows an increase in the reduction state of the plastoquinone pool. We
conclude that the heat stress-induced reduction of the intersystem electron
transport chain can be mediated by Ndh-independent pathways in the light but that
in the dark the dominant pathway for reduction of the plastoquinone pool is
catalysed by the Ndh complex. Our results therefore demonstrate a functional role
for the Ndh complex in the dark.
PMID- 9657395
TI - Restoration of phytanic acid oxidation in Refsum disease fibroblasts from
patients with mutations in the phytanoyl-CoA hydroxylase gene.
AB - Refsum disease (RD) is biochemically characterized by the excessive accumulation
of phytanic acid in tissues and body fluids due to deficiency of phytanoyl-CoA
hydroxylase (PAHX). In this study, we screened three RD patients and identified a
novel deletion (88 amino acids), and a missense mutation (Arg275Trp) in the
previously reported PAHX cDNA (Jansen et al., 1997; Mihalik et al., 1997).
Moreover, transfection of skin fibroblasts from two RD patients with wild-type
PAHX gene restored the activity for alpha-oxidation of phytanic acid. Southern
analysis on a somatic cell hybrid panel detected the PAHX gene on chromosome 10,
corroborating radiation hybrid and homozygosity mapping data (Mihalik et al.,
1997; Nadal et al., 1995).
PMID- 9657396
TI - Role of two conserved glycine residues in the beta-propeller domain of the
integrin alpha4 subunit in VLA-4 conformation and function.
AB - The N-terminal region of the alpha integrin subunits is predicted to fold into a
beta-propeller domain. Using K562 alpha4 transfectants we show that mutations at
alpha4 subunit residues Gly130 and Gly190 affect the conformation of this domain
causing a reduction in the recognition of alpha4 by anti-alpha4 antibodies which
map to the beta-propeller. The improper alpha4 conformation also led to an
altered association with the beta1 subunit, and to a lack of alpha4beta1 adhesion
to VCAM-1 and CS-1/fibronectin, as well as an abolishment of anti-alpha4- and
anti-beta1-dependent homotypic aggregation. The total conservation of Gly130 and
Gly190 among integrin alpha subunits suggests their importance in the correct
folding of their respective beta-propeller domains, and thus, in the adhesive
activity of the integrins.
PMID- 9657397
TI - Accreditation of echocardiography laboratories.
PMID- 9657398
TI - Safety of dobutamine stress echocardiography supervised by registered nurse
sonographers.
AB - Dobutamine stress echocardiography (DSE) is widely used for the diagnosis and
evaluation of coronary artery disease. Studies examining the safety of this
technique typically have involved DSE supervised by physicians. At the Mayo
Clinic, experienced registered nurse (RN) sonographers were trained to perform
DSE under the direct supervision of a physician. To prove that the safety of DSE
was not compromised with the change in supervision, we examined data from 1035
consecutive outpatient studies: 516 patients were monitored by cardiologists or
cardiology fellows (group 1) and 519 were monitored by trained RN sonographers
(group 2). Risk factors, history of coronary artery disease, stress parameters,
and complication rates were similar in both groups. In group 1, one patient
experienced sustained ventricular tachycardia requiring treatment. In group 2,
one patient experienced ventricular fibrillation during recovery and was
successfully resuscitated. Outpatient DSE is safe when supervised by RN
sonographers.
PMID- 9657399
TI - Prognostic implications of a normal dobutamine-atropine stress echocardiogram in
patients with chest pain.
AB - To assess the prognostic significance of a normal dobutamine-atropine stress
echocardiogram in relation to the pretest probability of coronary artery disease
(CAD), 200 consecutive patients (86 men and 114 women, mean [SD] age 59 [13]
years) with a stable chest pain syndrome and a normal dobutamine-atropine stress
echocardiogram were followed-up for 21 +/- 16 months. Outcome events were cardiac
death, non-fatal myocardial infarction, and coronary revascularization
procedures. Low (<10%), intermediate (10% to 80%), and high (>80%) pretest
probabilities of CAD were present in 27 (14%), 108 (54%), and 65 (33%) patients,
respectively. During follow-up, 2 patients (annual event rate 0.6%) had cardiac
death, none had nonfatal myocardial infarction, and 4 patients (annual event rate
1.1%) underwent a coronary revascularization procedure. All patients with cardiac
events had high pretest probabilities of CAD. Patients with cardiac death (but
unproven significant CAD) had maximal tests without angina or ischemic
electrocardiographic changes. In contrast, all patients with subsequent coronary
revascularization had dobutamine-induced angina or ischemic electrocardiographic
changes, and all except one study were submaximal. We conclude that patients with
a stable chest pain syndrome and normal findings on dobutamine-atropine stress
echocardiograms have an excellent cardiac prognosis. However, patients with
typical angina, high pre-test probabilities of CAD, and stress-induced angina or
ischemic electrocardiographic changes, and in particular those with submaximal
stress, still appear to be at risk for functionally important CAD despite a
normal dobutamine-atropine stress echocardiogram.
PMID- 9657400
TI - Assessment of coronary flow reserve by transesophageal echocardiography in
cardiac transplant recipients.
AB - This study investigated the feasibility of dipyridamole Doppler transesophageal
echocardiography to assess coronary flow reserve in 26 patients with orthotopic
heart transplantation and compared it with positron emission tomography. We found
an 85% success rate in obtaining Doppler flow signals in the proximal left
anterior descending coronary artery. Our data also showed that the correlation
between transesophageal echocardiography and dipyridamole N-13 ammonia positron
emission tomography increases when respective resting rate-pressure products are
taken into account. However, comparison between the two methods should be made
with caution because coronary flow reserve derived from transesophageal
echocardiography tends to be higher than that obtained with positron emission
tomography.
PMID- 9657401
TI - Left ventricular ejection fraction in patients with normal and distorted left
ventricular shape by three-dimensional echocardiographic methods: a comparison
with radionuclide angiography.
AB - BACKGROUND: Serial evaluation of left ventricular (LV) ejection fraction (EF) is
important for the management and follow-up of cardiac patients. Our aim was to
compare LVEF calculated from two three-dimensional echocardiographic (3DE)
methods with multigated radionuclide angiography (RNA), in patients with normal
and abnormally shaped ventricles. METHODS AND RESULTS: Forty-one consecutive
patients referred for RNA underwent precordial rotational 3DE acquisition of 90
cut-planes. From the volumetric data set, LVEF was calculated by (a) Simpson's
rule (3DS) through manual endocardial tracing of LV short-axis series at 3 mm
slice distance and (b) apical biplane modified Simpson's method ( MS) in 29
patients by manual endocardial tracing of the apical four-chamber view and its
computer-derived orthogonal view. Patients included three groups: A, 17 patients
with LV segmental wall motion abnormalities; B, 13 patients with LV global
hypokinesis; and C, 11 patients with normal LV wall motion. For all the 41
patients, there was excellent correlation, close limits of agreement, and
nonsignificant difference between 3DS and RNA for LVEF calculation (r = 0.99, [
6.7, +6.9] and p = 0.9), respectively. For the 29 patients, excellent correlation
and nonsignificant differences between LVEF calculated by both 3DS and BMS and
values obtained by RNA were found (r = 0.99 and 0.97, p = 0.7 and p = 0.5,
respectively). In addition, no significant difference existed between values of
LVEF obtained from RNA, 3DS, and BMS by the analysis of variance (p = 0.6). The
limits of agreement tended to be closer between 3DS and RNA (-6.8, +7.2) than
between BMS and RNA (-8.3, +9.7). The intraobserver and inter-observer
variability of RNA, 3DS, and BMS for calculating LVEF(%) were (0.8, 1.5), (1.3,
1.8), and (1.6, 2.6), respectively. There were closer limits of agreement between
3DS and RNA for LVEF calculation in A, B, and C patient subgroups [(-3.5, +5), (
8.4, +5.6), and (-7.8, +8.6)] than that between BMS and RNA [(-8.1, +10.7), (
11.9, +9.3), and (-9.1, +11.3)], respectively. CONCLUSIONS: No significant
difference existed between RNA, 3DS, and BMS for LVEF calculation. 3DS has better
correlation and closer limits of agreement than BMS with RNA for LVEF
calculation, particularly in patients with segmental wall motion abnormalities
and global hypokinesis. 3DS has a comparable observer variability with RNA.
Therefore the use of 3DS for serial accurate LVEF calculation in cardiac patients
is recommended.
PMID- 9657402
TI - Rates of left ventricular isovolumic pressure rise and fall from the aortic
regurgitation velocity signal: description of the method and validation in human
beings.
AB - BACKGROUND: Aortic regurgitation results from a pressure gradient across the
aortic valve during left ventricular (LV) isovolumic relaxation, LV filling, and
isovolumic contraction periods. Assuming the applicability of the simplified
Bernoulli equation to this pressure-flow relation and constancy of aortic
pressure during LV isovolumic relaxation and contraction periods, one can
theoretically obtain estimates of the rates of LV isovolumic pressure fall and
rise (deltaP/delta t) from the aortic regurgitation (AR) velocity signal. METHODS
AND RESULTS: Mitral regurgitation (MR) and AR signals were recorded by using the
continuous wave Doppler technique in 26 patients with combined mitral and aortic
regurgitant lesions. The LV negative deltaP/delta t was obtained by dividing the
time taken for the AR velocity to rise from 1 m/sec to 2.5 m/sec into 21 mm Hg,
which is the estimated LV pressure drop between these points. In a similar
fashion, the LV positive deltaP/delta t was obtained between 2.5 m/sec and 1
m/sec of the fast decelerating portion of the AR signal. The LV negative
deltaP/delta t by the AR method ranged from 420 to 3500 mm Hg/sec and correlated
well with that obtained by the MR method obtained in a blinded fashion (r = 0.95,
p < 0.0001). The mean (SD) difference between the two methods was 30 (129) mm
Hg/sec. Similarly, the LV positive deltaP/delta t by the AR method (range 420 to
2625 mm Hg/sec) correlated closely with that obtained by the MR method (r = 0.93,
p < 0.0001), with the mean (SD) difference between the two methods being 38 (138)
mm Hg/sec. CONCLUSIONS: Preliminary data presented in this study indicate the
feasibility of obtaining a reliable estimate of LV positive and negative
deltaP/delta t from the AR velocity profile. Thus the examination of the AR
signal may give valuable insights into both LV systolic and diastolic functions.
PMID- 9657403
TI - Role of intraoperative transesophageal echocardiography in determining aortic
annulus diameter in homograft insertion.
AB - The sizing of aortic valve (AV) homografts for optimum function requires an
accurate measurement of the aortic annulus. Typically, this measurement is
obtained directly with sizers in the open aorta. We describe the use of
intraoperative transesophageal echocardiography (IOTEE) to measure the aortic
annulus and select the appropriate AV homograft before cardiopulmonary bypass and
aortic cross-clamping. Thirty-two patients underwent AV homograft insertion
between March 1993 and March 1996 and had IOTEE. There were 13 women and 19 men.
Mean age was 58 +/- 14 years. IOTEE measurements were satisfactory in sizing in
all patients, and no extraordinary surgical measures were necessary to insert the
AV homografts. Early postoperative follow-up showed trivial or mild regurgitation
of all homografts. Prebypass IOTEE is reliable in guiding the selection of
optimal AV homografts.
PMID- 9657404
TI - Quantification of mitral regurgitation by the automated cardiac output method: an
in vitro and in vivo study.
AB - BACKGROUND: Recently, the automated cardiac output method (ACM) was introduced
for the calculation of blood flow at the left ventricular outflow tract (LVOT).
This study was performed to examine the possibility of using ACM for flow
calculation at the level of the mitral valve and for the quantification of mitral
regurgitation (MR) in vitro and in vivo. METHODS AND RESULTS: In a computer
controlled in vitro model of the human heart, aortic and mitral normal
bioprosthetic valves were inserted. ACM and electromagnetic probe flow
measurements correlated well at the LVOT and at the mitral level (r2 = 0.79 and
0.77, respectively). For stroke volumes ranging from 30 to 100 ml/beat, there was
no statistically significant bias between ACM and electromagnetic flow probe (
1.5 and 1.3 ml for LVOT and mitral level, respectively). Limits of agreement were
[-14; +11] ml and [-18; +16] ml, respectively. We evaluated 68 patients in our in
vivo study. They were divided into three groups according to the results of
"standard" echocardiographic Doppler methods for the semiquantification of MR:
echocardiographic color Doppler cartography, intensity of the continuous wave
Doppler spectra, and in some patients, pulmonary venous flow, conventional
Doppler, and proximal isovelocity surface area quantitative data. Group 1
consisted of 35 patients without MR or a physiologic one; the 17 patients in
group 2 had a mild MR (1-2/4) and in group 3, 16 patients with MR 3-4/4 were
included. Regurgitant volume (RV) was calculated as the difference between ACM
mitral flow and ACM aortic flow, and regurgitant fraction (RF) was defined as the
ratio between RV and ACM mitral flow. When mitral flow was measured only from the
four-chamber view, we found in group 1, RV = -0.57 (0.67) L/min and RF = -16%
(19%); in group 2, RV = -0.31 (1.06) L/min and RF = -8% (19%); and in group 3, RV
= 1.53 (0.94) L/min and RF = 23% (13%). RV and RF were statistically higher in
group 3 compared with group 2 or group 1 (p < 0.0005), but no significant
difference was found between groups 1 and 2. When mitral flow was measured by the
mean value of ACM four-chamber and two-chamber views, this resulted in group 1,
RV = -0.26 (0.63) L/min and RF = -8% (15%); in group 2, RV = 0.01 (1.04) L/min
and RF = -2% (18%); and in group 3, RV = 2.07 (1.21) L/min and RF = 34% (19%). RV
and RF were again significantly higher in group 3 (p < 0.0001). There was no
significant difference between group 1 and group 2, but in group 1 RF was no
longer statistically different from 0%. CONCLUSIONS: (1) In our in vitro setting,
ACM is reliable both at the LVOT and at the mitral valve. (2) In the in vivo
situation, some overlapping does exist between the three groups of MR. However,
ACM is a very easy, rapid, and objective method to differentiate hemodynamic
nonsignificant (<3/4) from significant (> or =3/4) MR. Together with other well
known methods for the quantification of MR, it should facilitate the gradation of
MR in the clinical setting. The absence of significant differences between group
1 and group 2 proves that the accuracy of ACM measurements at the mitral valve
needs to be ameliorated before ACM can be used as a gold standard for the
noninvasive measurement of RV and RF.
PMID- 9657405
TI - Evaluation of tricuspid regurgitation severity: echocardiographic and clinical
correlation.
AB - The correlation between 19 echocardiographic markers of tricuspid regurgitation
(TR) severity and findings on physical examination was studied in 66 consecutive
patients (age 63 +/- 12 years) with moderate or severe TR. Clinical TR was
defined by two or more of the following: prominent jugular venous pulse V waves,
pulsating liver, and sea-saw parasternal movement. Thirty-eight patients (57.6%)
had clinical TR, whereas 28 patients (42.4%) did not. In a univariate analysis,
the most powerful predictors of clinical TR (p < 0.01) were jet area > or =9 cm2,
right atrial area > or =30 cm2, jet width at origin > or =0.8 cm, systolic flow
reversal in the hepatic veins, paradoxical septal movement, diastolic septal
flattening, inferior vena cava diameter > or =2.1 cm, and lack of inferior vena
cava respiratory variation. Regurgitant index was a weaker predictor.
Multivariate analysis showed that the only independent echocardiographic
predictor of clinical TR was systolic flow reversal (positive and negative
predictive values 91.2% and 78.1%, respectively). Significant echocardiographic
TR can be subclinical in a substantial number of patients.
PMID- 9657406
TI - Visualization of clear echocardiographic images with near field noise reduction
technique: experimental study and clinical experience.
AB - BACKGROUND: With transthoracic echocardiography, it is sometimes difficult to
obtain a clear image of the apical portion of the heart because of noise near the
transducer. To reduce this artifact, we have developed a new technique (near
field noise reduction, NFNR) based on the digital filtering by using
radiofrequency signals. This technique may be useful for the accurate measurement
of the wall thickness of the myocardium in the near field. The objectives of
these studies were (1) to determine the accuracy of this new technique for the
measurement of wall thickness in the experimental study and (2) to determine
whether the improvement in the image quality in the apical portion can be
obtained in the clinical setting by using the NFNR technique. EXPERIMENTAL STUDY:
By using the NFNR technique, we measured wall thickness of three kinds of
phantoms (wall thickness 9.0, 14.0, and 21.0 mm) moving at various velocities (5
to 80 mm/sec) in the water bath with artifact produced by a single probe. It was
difficult to obtain clear echocardiographic images of the phantom and measure its
wall thickness because of the artifact. By using the NFNR technique, on the other
hand, the same phantom was clearly imaged. It was possible to measure the wall
thickness of each phantom at each moving velocity with the NFNR technique. Mean
differences between the echocardiographic measurement and actual value of wall
thickness in each phantom model (9.0, 14.0, and 21.0 mm) were 0.04 +/- 0.58 mm,
0.09 +/- 0.58 mm, and -0.02 +/- 0.24 mm, respectively. CLINICAL STUDY: We studied
25 initial patients in whom the near field was not clearly imaged in apical views
by conventional echocardiography because of near field noise. Apical four-chamber
or two-chamber views were obtained with and without the NFNR technique. Two
observers independently graded endocardial visualization for the 50 segments by
using a three-point scale (0 = endocardium not seen, 1 = seen in part but not all
of the segment, 2 = endocardium seen along entire segment). The mean segment
score in the imaging with the NFNR technique was significantly higher than that
without the NFNR technique (observer 1: 1.8 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01;
observer 2: 1.6 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01). CONCLUSIONS: The newly
developed NFNR technique provides clear echocardiographic images and accurate
wall thickness measurement in the experimental model even when it is difficult to
obtain clear images because of the artifact. This new technique will be useful in
the reduction of near field noise in the clinical setting.
PMID- 9657407
TI - Multiplane transesophageal echocardiography in diagnosis of anomalous origin of
the left coronary artery from the pulmonary artery: a case report.
AB - Anomalous origin of the left coronary artery from the pulmonary artery in adults
is difficult to identify reliably by transthoracic echocardiography (TTE). We
describe a 32-year-old woman with this coronary anomaly mimicking a coronary
artery fistula on conventional TTE study. This anomaly was suggested by
multiplane transesophageal echocardiography (TEE) and subsequently confirmed by
coronary angiography. Multiplane TEE thus may serve as a first-line diagnostic
tool for detecting anomalous origin of coronary arteries.
PMID- 9657408
TI - Anterior mitral valve aneurysm: evaluation by three-dimensional echocardiography.
AB - Three-dimensional reconstruction of cardiac structures is becoming increasingly
important. Complete spatial visualization of cardiac structures and their
relation to each other enable better understanding of both morphologic and
functional lesions.
PMID- 9657409
TI - Myxoma of the left atrial appendage mimicking thrombus during aortic valve
replacement.
AB - Echocardiographic characterization of cardiac masses involving the left atrium
are defined by morphologic shape and appearance, site of attachment, type of
margins, and presence or absence in the left atrial appendage. Most reports use
location in the LAA as strong supportive evidence of thrombus, especially if
associated with other suggestive findings (i.e., atrial fibrillation, spontaneous
echo contrast, or both). Other reported masses (non-thrombi) in the left atrial
appendage are considered extremely rare. We report a case of a patient with
coexisting aortic stenosis and atrial fibrillation diagnosed intraoperatively by
transesophageal echocardiography with myxoma of the left atrial appendage.
PMID- 9657410
TI - A case of hepatic hernia with echocardiographic findings simulating right atrial
tumor.
AB - A patient with hepatic hernia was found to have echocardiographic findings
resembling a right atrial tumor. Magnetic resonance imaging was useful in
establishing a definitive diagnosis of hepatic hernia. Hepatic hernias should be
ruled out when a right atrial tumor is suspected on the basis of transthoracic
echocardiographic findings.
PMID- 9657411
TI - Antisocial behavior: its relation to selected sociodemographic variables and
alcohol and drug use among Mexican students.
AB - This study is part of the National School Survey on drug use by high school
students in Mexico. The validity, reliability, and results of the Antisocial Acts
Scale in Mexico City (n = 3,501) are discussed. Using factorial analyses of the
Antisocial Acts Scale, two major sources of variability were observed. The first
one is related to antisocial acts with severe social consequences, in which
violence and drug selling are included, and the second one is related to thefts.
Significant differences were found in the number of offenses among groups of
different gender, age, and occupation during the previous year. More antisocial
acts were perpetrated by alcohol and drug users than by nonusers. In a logistic
regression model, it was found that the main risk factors for perpetrating
antisocial acts were being male, using alcohol, and using other drugs.
PMID- 9657412
TI - Children in the streets of Brazil: drug use, crime, violence, and HIV risks.
AB - The presence of vast numbers of unsupervised and unprotected children is a
phenomenon that is common throughout Latin America, and in few places are the
street children more visible, and reviled, than in Brazil. Estimates of their
numbers in Brazil have ranged from 7 to 17 million, but more informed assessments
suggest that between 7 and 8 million children, ages 5 to 18, live and/or work on
the streets of urban Brazil. Accounts of drug misuse among street youths in
Brazil are commonplace. Numerous scientific studies and media stories have
reported the widespread use of inhalants, marijuana and cocaine, and Valium among
street children. Also common is the use of coca paste and Rohypnol. Risk of
exposure to HIV is rapidly becoming an area of concern because of the large
number of street youths engaging in unprotected sexual acts, both renumerated and
nonrenumerated. Moreover, Brazil's street children are targets of fear. Because
of their drug use, predatory crimes, and general unacceptability on urban
thoroughfares, they are frequently the targets of local vigilante groups, drug
gangs, and police "death squads." Although there have been many proposals and
programs for addressing the problems of Brazilian street youth, it would appear
that only minimal headway has been achieved.
PMID- 9657413
TI - Psychosocial, substance use, and delinquency differences among Anglo, Hispanic
White, and African-American male youths entering a juvenile assessment center.
AB - Using data collected on nearly 4,000 Anglo, Hispanic White, and African-American
male youths processed at the Hillsborough County Juvenile Assessment Center, we
examine their psychosocial, substance use, and other delinquent behavior
differences. In extending the results of previous research in a manner consistent
with the concept of relative deviance, significant differences in these variables
are found across the three groups. Implications of the findings for theory,
service delivery, and policy are also considered.
PMID- 9657414
TI - Nurturing for careers in drug use and crime: conduct norms for children and
juveniles in crack-using households.
AB - A very sizable proportion of juvenile delinquents and adult criminals come from
backgrounds and family kin systems having deviant parents or kin. This paper
provides a focus upon the child-rearing practices directly observed by trained
ethnographer during a case study of one highly criminal, drug-using household/kin
network. The concrete expectations (and actual practices--called conduct norms-
with which the household adults respond to (or "nurture") children and juveniles
are delineated. While children are taught to "pay attention" to what adults do,
adults typically model various deviant activities and rarely engage in
conventional behaviors. Drug-using, and especially crack-using, men and women are
expected not to raise (or financially support) children born to them; other kin
expect to raise children of such unions. Children are not expected, nor able, to
develop strong affective bonds with any household adults, and receive little or
no psychological parenting. Adults do not take strong measures to protect
children/juveniles from harm, and often adults are a major source of harm. In
many ways the conduct norms in such crack-using households are well designed to
"nurture" those persons who will be antisocial as children, delinquents as
juveniles, and become criminals, drug misusers, and prostitutes in adulthood--and
who have very few chances to become conventional adults.
PMID- 9657415
TI - Using hair analysis, urinalysis, and self-reports to estimate drug use in a
sample of detained juveniles.
AB - This paper reports select findings of a research project designed to estimate
drug use prevalence in a youthful offender population using hair analysis as well
as urine testing and interviewing. The project was carried out in Cleveland,
Ohio, and Pinellas County, Florida. The findings are consistent with earlier
reports on prevalence estimations utilizing a bioassay component. Generally,
respondents report drug use infrequently and test positive by assays at rates
greater than self-reported use. Urinalysis indicates more drug prevalence than
does interview. Hair assays, which have a greater retrospective time window, show
even more prevalence than does urine testing. The project affirms results
reported in 1994 by Feucht, Stephens, and Walker.
PMID- 9657416
TI - HLA antigens in childhood onset schizophrenia.
AB - Evidence of immune system abnormalities in adult schizophrenia has prompted
examination of the human leukocyte antigen (HLA) system. Childhood onset
schizophrenia offers a unique opportunity to test neurodevelopmental hypotheses
of schizophrenia, including those which implicate components of the immune
system. In the present study, class I and II HLA antigens were typed using
sequence-specific primers and the polymerase chain reaction in 28 childhood onset
schizophrenics and 51 ethnically matched healthy subjects. Groups were compared
for frequencies of HLA antigens reported to be associated with schizophrenia
and/or autoimmune disorders. We hypothesized that antigen frequencies would
differ between schizophrenic and healthy children, suggesting that some dimension
of the neurodevelopmental disturbance experienced by these children may be
mediated by subtle abnormalities of immune function. There were no significant
differences between schizophrenic and healthy subjects in the frequency of any
antigen tested. These findings do not support HLA-associated pathology in
childhood onset schizophrenia.
PMID- 9657417
TI - Congenital dermatoglyphic malformations in severe bipolar disorder.
AB - Dermatoglyphic alterations may be the result of early prenatal disturbances
thought to be implicated in the aetiology of psychiatric illness. In order to
test this hypothesis in the particular case of bipolar disorder, we assessed two
congenital dermatoglyphic malformations (ridge dissociation (RD) and abnormal
features (AF)) and two metric dermatoglyphic traits (total finger ridge count
(TFRC) and total a-b ridge count (TABRC)) in a sample of 118 patients with
chronic DSM-III-R bipolar illness, and 216 healthy controls. Bipolar cases showed
a significant excess of RD and AF (OR = 2.80; 95% CI: 2.31-3.38) when compared
with controls. In the cases, the presence of anomalies was associated with
earlier age of onset. No differences were found for TFRC and TABRC. No
associations were found with sex or familial morbid risk of psychiatric
disorders. Our findings add further weight to the suggestion that early
developmental disruption is a risk factor for later bipolar disorder.
PMID- 9657418
TI - Cerebrospinal fluid prostaglandins and corticotropin releasing factor in
schizophrenics and controls: relationship to sleep architecture.
AB - Sleep abnormalities have been consistently observed in patients with
schizophrenia. Elevated levels of corticotropin releasing factor (CRF) and
prostaglandins (PGs) in the cerebrospinal fluid (CSF) of patients with
schizophrenia have been reported, and these neurochemical substances, known to
modulate sleep in experimental animals, may play a role in these sleep
abnormalities. In this study, we measured PGD2, PGE2, PGF2alpha and CRF levels in
the CSF of 14 unmedicated schizophrenic patients and 14 age- and sex-matched
control subjects. Polysomnographic recordings were also carried out for each
subject. As expected, the sleep of the schizophrenic subjects significantly
differed from that of the controls; schizophrenic subjects had a longer sleep
onset latency, slept less, spent fewer minutes in stage 2 sleep and had a lower
sleep efficiency. We could not, however, detect any differences in CSF CRF and PG
levels between normal and schizophrenic subjects, nor could we find any
correlation between CSF variables and sleep parameters in the schizophrenic
subjects and the non-psychiatric controls. These results do not favor the
hypothesis of a role for CRF or PGs in the pathophysiology of sleep disturbances
in schizophrenia.
PMID- 9657419
TI - Serotonin-immune interactions in detoxified chronic alcoholic patients without
apparent liver disease: activation of the inflammatory response system and lower
plasma total tryptophan.
AB - The aims of the present study were to examine (1) the inflammatory response
system (IRS), through measurements of serum interleukin-6 (IL-6), soluble IL-6
receptor (sIL-6R), sgp130 (the soluble form of the IL-6 transducer signal
protein), CC16 (Clara Cell protein; an endogenous anti-cytokine), IL-1R
antagonist (IL-1RA), IL-8 and sCD14; and (2) the availability of plasma total
tryptophan to the brain in chronic alcoholic patients without apparent liver
disease (AWLD). Detoxified AWLD patients had significantly lower plasma
tryptophan and serum CC16 and significantly higher serum IL-1RA and IL-8
concentrations than normal volunteers. There were significant correlations
between the availability of tryptophan to the brain and serum IL-6, IL-8 and IL
1RA (all negative) and CC16 (positive). The results suggest that (1) there is, in
detoxified AWLD patients, an activation of the monocytic arm of cell-mediated
immunity and a lowered anti-inflammatory capacity of the serum; and that (2)
lower availability of plasma tryptophan to the brain in detoxified AWLD patients
is related to activation of the IRS. Lower CC16 may be one factor predisposing
chronic alcoholic patients toward infectious disorders.
PMID- 9657420
TI - Platelet serotonergic functions and light therapy in seasonal affective disorder.
AB - We investigated platelet 14C-serotonin uptake and platelet [3H]LSD and
[3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD).
Patients were reinvestigated after light therapy, applied at 07.00-09.00 h for 10
consecutive days. The degree of depression was rated before and after light
therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline
data in patients were compared with data from a control group consisting of 11
age- and sex-matched healthy volunteers. Seven patients responded to light
therapy with a > 50% reduction in CPRS scores. In non-responders, the reduction
in CPRS was 24.7 +/- 5.5%. There was a significant inverse correlation (P =
0.014) between Km for platelet 14C-serotonin uptake and CPRS scores. Patients had
significantly higher Bmax for platelet [3H]LSD binding (P = 0.04) and
significantly lower Bmax for platelet [3H]paroxetine binding (P = 0.016). There
was a strong, multiple correlation between Bmax for [3H]LSD, as the dependent
variable, and Km, Vmax and Bmax for [3H]paroxetine binding in patients (P <
0.0001) but not in controls. Responders to light therapy had significantly higher
Km (P = 0.023) and significantly lower Bmax for [3H]paroxetine binding (P =
0.028) than non-responders. Bmax for [3H]paroxetine binding increased
significantly to normal levels after light therapy. The results indicate that SAD
is associated with aberrations in the serotonin uptake mechanism. The enhanced 5
HT2-receptor density may reflect a consequential up-regulation.
PMID- 9657421
TI - Platelet MAO activity in patients with dysthymic disorder.
AB - The aim of the present study was to examine possible associations between
platelet monoamine oxidase (MAO) activity and primary dysthymic disorder. For
that purpose we estimated the enzyme activity in 58 patients (15 males and 43
females) selected according to DSM-III-R criteria and in 61 healthy controls (30
males and 31 females). Platelet MAO activities were found significantly lower in
the female patients compared to female controls. Moreover, the enzyme activities
were found to be even lower in the female patients who had attempted suicide.
These differences did not exist in the male population. We could not find any
associations of MAO activity to the age of the patients, the age of onset, the
duration of dysthymia, or HAM-D and SCL-90R scores. Our findings are consistent
with the hypothesis that platelet MAO activity is a trait-dependent indicator of
vulnerability to dysthymic disorder and suicidality in our female population.
PMID- 9657422
TI - Premorbid personality traits of patients with organic (ICD-10 F0), schizophrenic
(F2), mood (F3), and neurotic (F4) disorders according to the five-factor model
of personality.
AB - The present article aims to examine premorbid personality traits of psychiatric
patients with various diagnoses by asking their close relatives to
retrospectively rate the patients' usual self with a questionnaire designed for
the five-factor model of personality, a rapidly emerging comprehensive theory of
personality structure. Data for 140 patients and 84 controls were analyzed.
Although psychiatric patients as a group were characterized by high neuroticism
and low conscientiousness when compared with the healthy controls, there were
only a few traits that distinguished a particular diagnostic group from either
the normal control or from the rest of the patients: neurotic disorder patients
had higher neuroticism scores than the normal controls; unipolar depressives had
a higher conscientiousness score than the rest of the patient group. No salient
premorbid trait was noted for patients with organic mental disorders,
schizophrenic disorders or bipolar disorders.
PMID- 9657423
TI - Factors that affect social cue recognition in schizophrenia.
AB - Earlier research (Corrigan and Green, Am. J. Psychiatry, 150 (1993) 589-594)
showed fairly symptomatic persons with schizophrenia give more false-positive
responses when answering questions about abstract cues in a social situation
(i.e. affect, rules, and goals inferred about an interpersonal situation) than
concrete cues (i.e. actions and dialogue observed in a situation). It is unclear,
however, whether differential cue recognition is due to schizophrenia per se, or
some aspect of the illness commensurate with significant symptoms and in-patient
care. Moreover, the abstract and concrete dimension in the earlier study had not
been independently validated. In this study, the 288 items of the Social Cue
Recognition Test (SCRT) were divided into three sets based on abstraction ratings
provided by 38 college students. The SCRT was then completed by 48 participants
with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder.
Participants with schizophrenia were divided into low and high symptom groups
using scores from the Brief Psychiatric Rating Scale. Results showed both low
symptom and high symptom groups exhibited a differential deficit in cue
recognition. False positives were greater for items rated as more abstract.
Implications for understanding the social cognitive deficits of persons with
schizophrenia are discussed.
PMID- 9657424
TI - Evaluation of problem solving and communication skills of persons with
schizophrenia.
AB - Although much research has shown positive outcomes of teaching problem solving
and communication skills to persons with schizophrenia, the amount of research on
the assessment of these two sets of skills has been modest. The current study
demonstrates an effective model for their assessment and includes a previously
neglected procedure to determine if subjects attended to the skill prompts. It
replicates and expands prior findings on problem solving and communication
skills. Results indicated that persons with schizophrenia were generally deficit
in problem solving skills. Persons without schizophrenia seemed to use more
behavioral information when deciding if a problem existed and they were better
able to differentiate between appropriate and inappropriate solutions to
problems. Persons with schizophrenia were found to be deficit in communication
skills that facilitate interaction and showed a style that subordinated their
wants to those of others.
PMID- 9657425
TI - Reliability of the 35% carbon dioxide panic provocation challenge.
AB - The objective of this study was to determine the test-retest reliability of the
35% carbon dioxide (CO2) panic provocation challenge. Thirty patients with panic
disorder were included in this study. Twenty-four patients were challenged twice,
with 1 week between the two challenges. Six patients dropped out after the first
test. The 35% CO2 challenge appeared to have a good test-retest reliability; both
on induced subjective anxiety, measured on a Visual Analogue Scale for Anxiety
(VAS-A), and induced panic symptoms, measured with a Panic Symptom List.
Assessing the state of anxiety immediately after the challenge gave the most
reliable results. Calculating increase in anxiety from the pre- and post-scores
on the VAS-A rendered less reliable scores. This study completes a series of
studies in which the criteria for an ideal model of panic are tested for the 35%
CO2 challenge. Apart from an absolute specificity for panic disorder, the
challenge meets these criteria.
PMID- 9657426
TI - Post-translational modifications required for coagulation factor secretion and
function.
PMID- 9657427
TI - Circulating ICAM-1 and VCAM-1 in peripheral artery disease and
hypercholesterolaemia: relationship to the location of atherosclerotic disease,
smoking, and in the prediction of adverse events.
AB - We examined the relationship of soluble intercellular adhesion molecule-1 (sICAM
1) and vascular cell adhesion molecule-1 (sVCAM-1) with smoking and
hypercholesterolaemia in peripheral artery disease (PAD). Serum samples were
obtained from 119 patients with objectively-proven PAD, 39 patients with
hypercholesterolaemia but asymptomatic for PAD, and 132 age and sex matched
asymptomatic controls. Using ELISAs, we found increased sICAM-1 and sVCAM-1 (both
p <0.01) in the patients with PAD relative to the controls, but no significant
change in patients with hypercholesterolaemia. However, the effect for sVCAM-1
was lost when smoking was entered as a covariate. Only sICAM-1 was higher in
patients with PAD in the femoral/iliac arteries compared to the carotid arteries
(p <0.05). In a 39-month follow-up of 112 patients with PAD, increased ICAM-1
weakly (univariate p <0.05) predicted those 57 whose disease progressed (i.e. to
end points such as myocardial infarction and arterial surgery). However, high
fibrinogen was a much better (univariate p = 0.001, multivariate p <0.05)
predictor of disease progression. We suggest (i) that increased levels of sVCAM-1
in atherosclerosis are due to smoking, (ii) that increased sICAM-1 is independent
of this risk factor, (iii) that both these changes are independent of
hypercholesterolaemia, and (iv) that increased sICAM-1 is a weak predictor of
disease progression in peripheral atherosclerosis.
PMID- 9657428
TI - A novel mutation in intron K of the PROS1 gene causes aberrant RNA splicing and
is a common cause of protein S deficiency in a UK thrombophilia cohort.
AB - In the course of investigating the molecular basis of protein S deficiency in 31
index cases with thrombophilia, we identified seven kindred where the underlying
defect was a novel A to G transition 9 bp upstream of exon 12 in intron K of the
PROS1 gene. In all but one case, the mutation caused type I deficiency. One
individual had type III deficiency. While ectopic transcript analysis using the
BstXI dimorphism in exon 15 failed to detect a transcript from the mutated
allele, analysis of transcripts spanning exons 11 and 12 revealed a minor mRNA
species. Sequencing confirmed the mutation created a new RNA acceptor site
introducing 8 nucleotides of intronic sequence into the mature mRNA. Haplotype
analysis of the defective PROS1 alleles in six families revealed the same
haplotype in all affected individuals suggesting the presence of a common
ancestor. Six of the fourteen relatives with the mutation experienced at least
one venous thrombotic event strongly supporting the association of the mutation
with venous thrombosis.
PMID- 9657429
TI - Predictive value of plasma thrombomodulin in preeclampsia and gestational
hypertension.
AB - In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia
were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin
(pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after
delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or
gestational hypertension (n = 12) between weeks 32 and 39 of gestation and in 25
(age-matched) primigravidae who had uneventful pregnancies. pTM elevations were
not observed until week 32 in uneventful pregnancies, but were present by week 24
(p = 0.002) in patients who later developed hypertensive complications. A net
individual pTM increase > or = 4.2 ng/ml between weeks 12 and 24 (more than 8
times that of normotensive primigravidae) and/or pTM level > or = 47.5 ng/ml at
week 32 predicted the development of hypertensive complications with 80%
accuracy. Serial pTM determinations can be useful to select pregnancies who may
benefit from early pharmacological intervention.
PMID- 9657430
TI - Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease.
AB - Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial
aneurysms and myocardial infarction in young children. Prominent thrombocytosis
with increased megakaryocytes develops during the convalescent period. To clarify
the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO)
and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106
age-matched controls using ELISA. TPO values in the controls were 1.94 +/- 0.69
fmol/ml (mean +/- SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In
the first week of KD, platelet counts were normal but TPO values increased
(approximately 15.5 fmol/ml). TPO levels peaked on day 6 +/- 2 at 5.94 +/- 2.64
fmol/ml and then fell gradually. When platelet counts peaked in the second to
third weeks, TPO levels were still high or comparable with the controls. TPO
levels in KD patients with normal platelet counts were significantly higher than
control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL
11 nor leukemia inhibitory factor was detectable. These results suggest that TPO
contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production
may be enhanced during the acute phase.
PMID- 9657431
TI - The diagnostic value of thrombopoietin level measurements in thrombocytopenia.
AB - It has been reported that blood trombopoietin (TPO) levels can discriminate
between thrombocytopenia due to increased platelet destruction and decreased
platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a
large group of patients in detail and could confirm and amplify the above notion
in detail. TPO levels were determined in plasma from 178 clinically and
serologically well-defined thrombocytopenic patients: 72 patients with idiopathic
autoimmune thrombocytopenia (AITP), 29 patients with secondary AITP, 5 patients
with amegakaryocytic thrombocytopenia and 72 patients who suffered from various
diseases (46 in whom megakaryocyte deficiency was not and 26 in whom it was
expected). In addition, we measured the level of glycocalicin as a marker of
total body mass of platelets. In all patients with primary AITP and secondary
AITP, TPO levels were within the normal range or in some (n = 7) cases only
slightly increased. The level of glycocalicin was not significantly different
from that of the controls (n = 95). The patients with amegakaryocytic
thrombocytopenia had strongly elevated TPO levels and significantly decreased
glycocalicin levels. Similarly, among the 72 thrombocytopenic patients with
various disorders, elevated TPO levels were only found in patients in whom
platelet production was depressed. The mean level of glycocalicin in these
patients was decreased compared to that in controls and patients with AITP, but
was not as low as in patients with amegakaryocytic thrombocytopenia. In
conclusion, all patients with depressed platelet production had elevated levels
of circulating TPO, whereas the TPO levels in patients with an immune-mediated
thrombocytopenia were mostly within the normal range. Therefore, measurement of
plasma TPO levels provides valuable diagnostic information for the analysis of
thrombocytopenia in general. Moreover, treatment with TPO may be an option in
AITP.
PMID- 9657432
TI - Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous
measurement of reticulated platelets of whole blood and serum thrombopoietin
concentrations.
AB - To evaluate thrombopoiesis in thrombocytopenic disorders, we simultaneously
determined reticulated platelet counts in whole blood by FACScan flow cytometry
and serum thrombopoietin (TPO) concentrations by a sensitive sandwich ELISA. The
subjects were 40 healthy volunteers and 45 thrombocytopenic patients. In
idiopathic thrombocytopenic purpura (ITP), the percentage of reticulated
platelets was significantly elevated (5.61 +/- 2.02%: mean +/- SD) relative to
normal controls (2.17 +/- 0.90%), but serum TPO concentrations (1.91 +/- 1.27
fmol/l) did not differ significantly from the normal range (1.43 +/- 0.62
fmol/l). The patients with aplastic anemia (AA) had decreased reticulated
platelet counts and markedly increased serum TPO concentrations (13.65 +/- 10.64
fmol/l). In thrombocytopenic patients with liver cirrhosis (LC), the absolute
number of reticulated platelets (1.65 +/- 1.11 x 10(9)/l) decreased similarly
that in AA. However, serum TPO concentrations (1.38 +/- 0.50 fmol/l) did not
increase in contrast to AA. Our findings suggested a possible dual mechanism of
thrombocytopenia in LC; that is, thrombocytopenia in LC results from the
decreased TPO production primarily in the liver adding to an increase in platelet
sequestration in the spleen.
PMID- 9657433
TI - Significant correlations between tissue factor and thrombin markers in trauma and
septic patients with disseminated intravascular coagulation.
AB - To determine the role of plasma tissue factor on disseminated intravascular
coagulation (DIC) in trauma and septic patients, and also to investigate the
relationships between tissue factor and various thrombin markers, we made a
prospective cohort study. Forty trauma patients and 20 patients with sepsis were
classified into subgroups according to the complication of DIC. Plasma tissue
factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2),
thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were
measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after
admission. The levels of plasma tissue factor in the DIC group were more elevated
than those of the non-DIC group in both the trauma and the septic patients. In
patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC
group showed markedly higher values than those in the control patients (135 +/- 8
pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D
dimer were observed in the DIC patients, however, no such correlations were found
in the non-DIC patients. These results suggest that elevated plasma tissue factor
in patients with trauma and sepsis gives rise to thrombin generation, followed by
intravascular coagulation.
PMID- 9657434
TI - Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin.
AB - BACKGROUND: Patients receiving long-term warfarin frequently develop asymptomatic
excessive prolongation of their international normalized ratio (INR) results. The
most appropriate management strategy in these patients is unknown. This
prospective cohort study was designed to address whether 1 mg of oral vitamin K
effectively reduces the INR value of such patients. METHODS: A prospective cohort
study was performed in two tertiary care teaching hospitals, in which 62 patients
receiving warfarin who had INR values between 4.5 and 10.0 received 1 mg of oral
vitamin K. All patients had daily INR values and clinical assessments performed.
RESULTS: The mean INR value at presentation was 5.79 (95% confidence interval
(CI) 5.48 to 6.09, range 4.5 to 9.5). Sixteen hours after receiving the 1 mg of
oral vitamin K, the mean INR was 2.86 (95% CI 2.50 to 3.23). On the second and
third days after vitamin K, the mean INR values were 2.20 (1.93 to 2.47) and 2.14
(1.85 to 2.44), respectively. No adverse events or bleeding complications were
observed. In three patients (6%) the INR value rose between the time of vitamin K
administration and the next INR determination; two patients received a further 2
mg dose of subcutaneous vitamin K. CONCLUSIONS: In patients receiving warfarin
who have asymptomatic excessive prolongations in their INR results, 1 mg of oral
vitamin K reliably reduces the INR to the therapeutic range within 24 h. This
therapy is more convenient, less expensive, and might be safer than parenteral
vitamin K. Thus, it should be considered in all non-bleeding patients receiving
warfarin, who present with INR results of 4.5 to 9.5.
PMID- 9657435
TI - Increased potency and decreased elimination of lamifiban, a GPIIb-IIIa
antagonist, in patients with severe renal dysfunction.
AB - Activation of the platelet membrane receptor glycoprotein (GP) IIb-IIIa is
essential for thrombus formation. The novel nonpeptide GPIIb-IIIa antagonist,
lamifiban, represents a promising approach for antiplatelet therapy in patients
with cardiovascular disease. Since renal impairment frequently occurs in these
patients, we designed a phase I study to assess the tolerability,
pharmacodynamics and pharmacokinetics of lamifiban in patients with renal
impairment. Four healthy volunteers (Group 1) with creatinine clearance (CLCR)
>75 ml/min, eight patients (Group 2) with mild to moderately impaired renal
function (CLCR 30-74 ml/min) and eight patients (Group 3) with severe renal
impairment (CLCR 10-29 ml/min) were studied. They received stepwise increased
doses of lamifiban intravenously (i.v.). There was a linear relationship between
the systemic clearance of the drug and renal function (R2 = 0.86). The mean
plasma concentration required for half-maximal inhibition of thrombin-receptor
agonist peptide (TRAP) induced platelet aggregation (EC50) ex vivo was 21, 28 and
11 ng/ml in Groups 1, 2 and 3. The patients in Group 3 were sensitized to the
antiplatelet effect allowing an 18-fold dosage reduction without compromising the
pharmacodynamics. In conclusion, the decreased clearance of lamifiban may act in
concert with increased potency of the drug in patients with severe renal
impairment, and the drug dosage should be reduced accordingly.
PMID- 9657436
TI - Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary
stenosis.
AB - Based on genetic variability, structural differences in the glycoprotein IIb/IIIa
platelet receptor for adhesive proteins result in individual differences in the
thrombogenicity of platelets. Recent studies suggest a controversial association
between a genetic polymorphism of the glycoprotein IIIa gene (PlA2) and the risk
of coronary artery disease. In our study, the prevalence of the PlA2 allele in a
group of patients undergoing percutaneous coronary revascularization was 37%, a
value significantly higher than in controls [13%, odds ratio (OR) = 3.93, 95% CI,
1.84 to 8.53] suggesting a significant association between this polymorphism and
documented coronary stenosis, which is strongest among <60 years old patients (OR
= 12.30, 95% CI, 2.98 to 70.93). This polymorphism represents an inherited risk
factor for severe cardiovascular disease due to coronary occlusion.
PMID- 9657438
TI - Characterization of a factor VII molecule carrying a mutation in the second
epidermal growth factor-like domain.
AB - A missense mutation at codon 100 in the second epidermal growth factor-like
domain, resulting in Gln100-->Arg, was detected in 19 out of 21 available
severely factor VII (FVII) deficient patients in Norway. Seventeen patients were
homozygous, and the two remaining were compound heterozygotes. In the homozygous
patients, FVII antigen was measured to 10-28%, and activity to 0.6-6.5% of that
in normal pooled plasma. Recombinant FVII containing the mutation was expressed
transiently in CHO cells to a mean antigen level of 57% of the wild type FVII
protein, and with a specific activity of 6% of wild type. The mutant protein had
a 14-fold reduction in affinity for tissue factor (TF), whereas binding of FX
seemed unaffected. In line with the experimental data, molecular modelling of the
mutation based on the coordinates of the tissue factor/FVIIa complex showed that
substituting arginine for glutamine disrupts the interface between the catalytic
and second epidermal growth factor-like domains.
PMID- 9657437
TI - Comparison of a synthetic antithrombin III-binding pentasaccharide and standard
heparin as an adjunct to coronary thrombolysis.
AB - The effects on alteplase-induced thrombolysis of the synthetic ATIII-binding
pentasaccharide SR90107A/ORG 31540 (synthetic pentasaccharide, SP) and of
standard heparin (SH) were compared in a copper coil model of coronary artery
thrombosis in 6 groups of 10 dogs. After 1 h of occlusion, all animals received
intravenously alteplase and aspirin, and were randomly assigned to a 2 h infusion
of either saline, or one of two doses of SH (100 IU/kg bolus plus 50 IU/kg/h
infusion, or 200 IU/kg bolus plus 100 IU/kg/h infusion), or one of three doses of
SP (100 nmol/kg bolus plus 50 nmol/kg/h infusion, 200 nmol/kg bolus plus 100
nmol/kg/h infusion, or 400 nmol/kg bolus plus 200 nmol/kg/h infusion). Coronary
angiography was performed every 10 min for 4 h. Appropriate doses of SP and SH
enhanced alteplase-induced thrombolysis to a similar extent. In contrast, SP was
devoid of any anti-IIa activity or aPTT prolongation.
PMID- 9657439
TI - Identification of a glucocorticoid response element in the human gamma chain
fibrinogen promoter.
AB - The effect of the synthetic glucocorticoid hormone dexamethasone on human gamma
chain fibrinogen gene expression was examined. The whole promoter region of 3.8
kb of this gene and progressive 5'-deletions were inserted into a promoterless
expression vector, upstream of the luciferase gene and transiently transfected
into the human hepatoma HepG2 cells, in the presence or in the absence of
dexamethasone stimulation. Deletion analysis allowed to identify a region located
between -1359 and -954 bp upstream from the transcription start site, involved in
hormone inducibility. On the basis of a computer-assisted analysis, a putative
GRE was found in this region at bases -1116 to -1102. Specific point mutations
eliminating this putative GRE led to complete loss of glucocorticoid
inducibility, thus indicating its functional role. Binding of the rat
glucocorticoid receptor to this site was demonstrated by mobility-shift assays.
PMID- 9657440
TI - New splicing mutations in the human factor XIIIA gene, each producing multiple
mutant transcripts of varying abundance.
AB - Coagulation factor XIII, a transglutaminase which stabilises blood clots by
covalently cross-linking fibrin, is essential for normal haemostasis. FXIII
deficiency results in a life-long bleeding disorder with added complications in
wound healing and tissue repair. Sequence changes in the human FXIIIA gene,
largely missense mutations, are primarily responsible for inherited FXIII
deficiency. We have carried out molecular analysis of the FXIIIA gene in two
unrelated FXIII deficient individuals and identified three splice site mutations;
a g-->a at the exon 6 acceptor splice site, a g-->a at the exon 7 donor splice
site and a coding sequence T-->G at the exon 8 donor splice site. We have also
examined the FXIIIA mRNA in these patients and find that each mutation gives rise
to multiple transcripts which vary in their relative abundance. The precise
molecular mechanisms which result in these variant transcripts, and their
relative abundance in our FXIII deficient patients, are discussed.
PMID- 9657441
TI - Inhibition of thrombin-catalyzed factor V activation by bothrojaracin.
AB - We have previously identified and characterized a potent and specific thrombin
inhibitor, isolated from Bothrops jararaca, named bothrojaracin. Bothrojaracin
interacts with the two positively charged recognition sites of thrombin referred
to as exosite 1 and exosite 2, whereas it does not interact with the thrombin
active site. Consequently, bothrojaracin inhibits thrombin-induced fibrinogen to
fibrin conversion and platelet activation, without inhibition of thrombin
catalyzed cleavage of small synthetic substrates. In the present study, we show
that bothrojaracin exerts an anticoagulant effect in plasma, illustrated by the
prolongation of the aPTT. Using purified proteins, we observed that the
anticoagulant effect of bothrojaracin was not only due to the inhibition of
fibrinogen to fibrin conversion, but in addition to the inhibition of factor V
activation by thrombin. Bothrojaracin decreased the rate of thrombin-catalyzed
proteolysis of factor V and concurrently the generation of factor Va cofactor
activity measured in a prothrombinase assay. We compared the effect of
bothrojaracin with that of ligands binding specifically exosite 1 (hirudin C
terminal peptide SH54-65) or exosite 2 (heparin, prothrombin fragment 2). SH54-65
delayed thrombin catalyzed factor V activation whereas heparin or prothrombin
fragment 2 did not. The thrombin derivatives beta- and gamma-thrombin, which are
defective in their exosite 1, but present with a normally exposed exosite 2, had
a reduced capacity to activate factor V, which was not further impaired by the
exosite 2 ligands, bothrojaracin, heparin or prothrombin fragment 2. Altogether,
our results provide further insight into the anticoagulant effect of
bothrojaracin showing that it is a potent inhibitor of the feedback activation of
factor V by thrombin, and thus of the up-regulation of its own production by
thrombin. Inhibition of thrombin-catalyzed factor V activation by bothrojaracin
is mainly mediated through the interaction of the inhibitor with thrombin exosite
1, whereas contribution of the interaction with exosite 2 does not appear to play
a direct role in factor V recognition by thrombin.
PMID- 9657442
TI - Aging and venous thromboembolism influence the pharmacodynamics of the anti
factor Xa and anti-thrombin activities of a low molecular weight heparin
(nadroparin).
AB - Venous thromboembolism may be efficiently treated by one single daily
administration of a high dose of low molecular weight heparin (LMWH). The present
study investigates if the physiological deterioration of renal function
associated with normal aging or the presence of an acute venous thromboembolism
influences the pharmacodynamic pattern of the anti-factor Xa and anti-thrombin
activities. Three groups of 12 subjects were investigated. The first 2 groups
were composed of healthy volunteers differing by age (25 +/- 4 and 65 +/- 3 yrs)
and creatinine clearance (114 +/- 15 and 62 +/- 6 ml x min(-1)). The third group
was composed of patients hospitalized for deep vein thrombosis, having a mean age
of 65 +/- 11 yrs and creatinine clearance of 76 +/- 8 ml x min(-1). Nadroparin
was administered subcutaneously once daily at the dose of 180 anti-factor Xa
IU.kg(-1) for 6 to 10 days. Serial sampling on day 1 and on the last day of
administration (day n) allowed the pharmacodynamic parameters of the anti-factor
Xa and anti-thrombin activities to be compared at the beginning and at the end of
the treatment. The main findings were the following: (1) After repeated
administration, a significant accumulation of the anti-factor Xa activity was
observed in the healthy elderly and in the patients but not in the healthy young
subjects (accumulation factor: 1.3). There was no evidence of accumulation of
anti-thrombin activity; (2) There were significant correlations between the
clearance of creatinine and the clearance of the anti-factor Xa activity but not
with that of the anti-thrombin activity; (3) In the patients, the clearance of
the anti-factor Xa and of the anti-thrombin activities were 1.4 and 2 times
higher respectively than those calculated in the healthy elderly; (4) The mean
ratio of the of anti-factor Xa and anti-thrombin clearances was close to 2 in the
healthy subjects but equal to 5.4 in the patients. These results suggest that the
mechanisms involved in the clearance of polysaccharide chains which support the
anti-thrombin activity are different from those of the anti-factor Xa activity
and that the enhanced binding properties of plasma proteins to unfractionated
heparin reported in patients presenting an acute venous thromboembolism also
exists for LMWH, predominantly for the anti-thrombin activity.
PMID- 9657443
TI - Activated protein C sensitivity, protein C, protein S and coagulation in normal
pregnancy.
AB - A prospective study of activated protein C sensitivity, protein C, protein S, and
other coagulation factors in 239 women during normal pregnancy was carried out.
Protein C activity appeared unaffected by gestation, although an elevation of
protein C activity was observed in the early puerperium. A fall in total and free
protein S with increasing gestation was observed. Activated protein C sensitivity
ratio (APC:SR) showed a progressive fall through pregnancy. This fall correlated
with changes in factor VIIIc, factor Vc and protein S. 38% of subjects, with no
evidence of Factor V Leiden or anticardiolipin antibodies, showed a low APC:SR
(APC:SR <2.6) in the third trimester of pregnancy. Aside from a significant
reduction in birth weight, no difference in pregnancy outcome was observed
between these subjects and those with a normal APC:SR. Activated protein C
sensitivity ratio, modified by pre-dilution of patient samples with factor V
depleted plasma, showed no consistent trend with gestation.
PMID- 9657444
TI - Regulation of gelatinase activity in mice with targeted inactivation of
components of the plasminogen/plasmin system.
AB - To investigate a potential physiological role of the plasminogen/plasmin system
in activation of the matrix metalloproteinase (MMP) system, the distribution of
latent and active MMP-2 (gelatinase A) or MMP-9 (gelatinase B) was monitored in
aorta extracts and in serum-free conditioned cell culture medium obtained from
wild-type (WT) mice and from mice with deficiency of tissue-type plasminogen
activator (t-PA(-/-)), urokinase-type plasminogen activator (u-PA(-/-)),
plasminogen activator inhibitor-1 (PAI-1(-/-)) or plasminogen (Plg(-/-)). In
aorta extracts, the contribution of active MMP-2 to the total MMP-2 level ranged
between 7 and 16% for the different genotypes, whereas active MMP-9 was not
detected. The contribution of active 58 kDa MMP-2 to the total MMP-2 level
(active plus latent) ranged between 14 and 29% (mean of 3 experiments) for
fibroblasts of the different genotypes, and between 18 and 32% for smooth muscle
cells, and was relatively constant in time (7-72 h). The contribution of active
83 kDa MMP-9 to the total MMP-9 level ranged between 15 and 29% for fibroblasts
of the different genotypes and was relatively constant in time (24-72 h);
corresponding values were 17 to 57% for smooth muscle cells, with the exception
of Plg(-/-) smooth muscle cells which had undetectable levels of active MMP-9.
Addition of plasmin(ogen) to the cell culture medium of fibroblasts did not
significantly affect the distribution of active and latent MMP-2, but resulted in
an approximately two-fold enhancement of the contribution of active MMP-9. In
macrophages of Plg(-/-) mice, active MMP-9 was detected only when the cells were
cultured in the presence of plasminogen. These data indicate that activation of
proMMP-2 occurs independently of the physiological plasminogen activators and of
plasmin(ogen) in all the cell types evaluated. Activation of proMMP-9 was
enhanced in the presence of plasmin(ogen), but active MMP-9 was also detected in
fibroblasts of Plg(-/-) mice, indicating that in vivo activation may occur via
plasmin(ogen)-independent mechanisms.
PMID- 9657445
TI - Neutrophils rolling on immobilised platelets migrate into homotypic aggregates
after activation.
AB - Interactions between platelets and leucocytes are implicated in the pathology of
thrombotic vascular disease. Using a flow-based adhesion assay we have
investigated a novel route for the formation of neutrophil aggregates on the
surface of immobilised activated platelets. Neutrophils perfused over a platelet
monolayer formed numerous rolling attachments but rapidly stopped and spread
after the superfusion of N-formyl-methionyl-leucyl-phenylalanine or platelet
activating factor (both at 10(-7) M). Subsequent integrin-mediated migration
across the platelet monolayer enabled formation of homotypic neutrophil
aggregates, which was significant within 2.5 min of receipt of either stimulus.
Aggregates increased in size with time and had an average projected area of
approximately 500 microm2 after 10 min. Increasing size was correlated with an
increasing tendency for movement downstream and large aggregates sometimes
tumbled in that direction. The formation and stability of homotypic aggregates
was dependent on several adhesive mechanisms. Antibody blockade demonstrated that
interactions involving CD11a/CD18 and ICAM-3, between alpha(v)beta3-integrin and
CD31 and between L-selectin and an unidentified counter-ligand were all required
for the complete aggregatory response. Furthermore, blockade of L-selectin
allowed initial aggregation which then reversed, suggesting that this receptor
might regulate the interactions between other adhesion molecules that directly
supported cell-cell adhesion. We propose that this novel route for leucocyte
aggregation could promote vascular occlusion in thrombotic vessels or at distal
sites in the event of embolisation.
PMID- 9657447
TI - On the mechanism of plasmin-induced aggregation of human platelets: implication
of secreted von Willebrand factor.
AB - Plasmin triggers a strong metabolic activation in human platelets, leading to
shape change and granule exocytosis. However, its capacity to induce cell
aggregation remains discussed and, when observed, this aggregation is preceded by
a remarkable lag phase. We have thus investigated the effect of plasmin on the
adhesive proteins which can be secreted by isolated platelets and mediate cell-to
cell interactions, but are also substrates for the enzyme. Immunoblot analysis of
fibrinogen (Fg), thrombospondin-1 (TSP-1), fibronectin (Fn) and von Willebrand
factor (vWf) was performed on extracts of platelets exposed under stirring to
increasing concentrations of plasmin for up to 10 min at 37 degrees C. Under
conditions leading to formation of large aggregates, Fg, Fn and TSP-1 are
extensively degraded concomitantly with their secretion, and readily lost from
the surface of aggregated cells. Part of the monomers in the platelet vWf are
cleaved during secretion into two main fragments with Mr approximately 180,000
and approximately 145,000. However, multimer distribution analysis shows only a
slight decrease in the very high molecular weight multimers, and most of the
fragmented as well as intact vWf remains associated with the platelet surface
when aggregation is maximal. That indeed vWf largely supports plasmin-induced
aggregation is suggested by the observation that platelets from a patient with
type 3 von Willebrand's disease, who totally lacks vWf, show little aggregation
in response to the enzyme. Finally, plasmin-induced aggregation can be totally
inhibited by antagonists of the alpha(IIb)beta3 integrin. The present study thus
indicates a major role for secreted vWf in platelet aggregation induced by
plasmin, through its likely interaction with the multifunctional receptor
alpha(IIb)beta3.
PMID- 9657446
TI - Difference of (Ca2+)i movements in platelets stimulated by thrombin and TRAP: the
involvement of alpha(IIb)beta3-mediated TXA2 synthesis.
AB - This study investigated the difference of [Ca2+]i movement in platelets in
response to thrombin and TRAP. The involvement of alpha(IIb)beta3 in this
signaling was also studied. Stimulation of platelets with thrombin at 0.03 U/ml
caused platelet aggregation and a two-peak increase in [Ca2+]i. The second peak
of [Ca2+]i, but not the first peak was abolished by the inhibition of platelet
aggregation with alpha(IIb)beta3 antagonists or by scavenging endogenous ADP with
apyrase. A cyclooxygenase inhibitor, aspirin, and a TXA2 receptor antagonist, BM
13505, also abolished the second peak of [Ca2+]i but not the first peak, although
these regents did not inhibit aggregation. Under the same assay conditions,
measurement of TXB2 demonstrated that alpha(IIb)beta3 antagonists and aspirin
almost completely inhibited the production of TXB2. In contrast to thrombin
stimulation, TRAP caused only a single peak of [Ca2+]i even in the presence of
platelet aggregation, and a high level of [Ca2+]i increase was needed for the
induction of platelet aggregation. The inhibition of aggregation with
alpha(IIb)beta3 antagonists had no effect on [Ca2+]i change and TXB2 production
induced by TRAP. Inhibition studies using anti-GPIb antibodies suggested that
GPIb may be involved in the thrombin response, but not in the TRAP. Our findings
suggest that low dose thrombin causes a different [Ca2+]i response and TXA2
producing signal from TRAP. Endogenous ADP release and fibrinogen binding to
alpha(IIb)beta3 are responsible for the synthesis of TXA2 which results in the
induction of the second peak of [Ca2+]i in low thrombin- but not TRAP-stimulated
platelets.
PMID- 9657448
TI - The cDNA cloning and molecular characterization of a snake venom platelet
glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii
venom.
AB - The entire cDNA sequences of a novel snake venom platelet glycoprotein (GP) Ib
binding protein (BP) composed of an alpha/beta heterodimeric structure, termed
mamushigin, from Agkistrodon halys blomhoffii were determined, that include the
leader peptides (21/23 amino acid residues) and mature subunits (136/123 amino
acid residues). The mature subunits of mamushigin are 37.5% identical, and showed
a high degree of similarity (37.7-67.5% identity) with the respective subunits of
group VII C-type lectins (19). The sequences of the leader peptides of the
mamusigin subunits showed the highest similarity (alpha-73.9/beta-82.6%) with
those of factor IX/X-BP from Trimeresurus flavoviridis, and the cleavage site
residue in both proteins was the same Ala(-1). The GPIb-binding specificity of
mamushigin is strongly supported by several lines of evidence, but mamushigin can
directly aggregate normal platelets, similar to alboaggregin-B (AL-B) (1). This
differs from other GPIb-BP's. In mamushigin-treated platelets, serotonin was not
released, and flow cytometric analysis using a monoclonal antibody PAC-1 totally
excluded platelet GPIIb/IIIa activation. Mamushigin enhanced platelet aggregation
at low-shear stress, and this effect totally disappeared in the presence of GPIb
receptor blockers specific for von Willebrand factor binding, but not by
GPIIb/IIIa-receptor blockers. At high-shear stress, mamushigin blocked platelet
aggregation in a dose-dependent manner, as seen with other GPIb-BP's. This paper,
therefore, describes the cDNA cloning and molecular characterization of
mamushigin which has a different effect on platelet aggregation under different
shear stress.
PMID- 9657449
TI - Nitric oxide and prostacyclin are involved in antithrombotic action of captopril
in venous thrombosis in rats.
AB - The long-term administration of captopril to patients with a left ventricular
dysfunction after myocardial infarction reduces the rate of recurrent coronary
thrombosis. Thus, in the present study we investigated the influence of
angiotensin-converting enzyme inhibitors (ACE-Is) on experimental venous
thrombosis in normotensive rats and the involvement of NO and PGI2 in this
effect. Animals were treated with captopril (1.5, 5 or 25 mg/kg twice daily,
CAP), enalapril (15 mg/kg once daily, ENA) or distilled water for 10 days, per
os. After ligation of the vena cava the thrombus weight decreased in both CAP and
ENA treated rats. The effect was most pronounced in animals given the highest
dose of CAP (p<0.0001 vs. control) and was significantly stronger than observed
in ENA treated animals (CAP vs. ENA p<0.01). The mean blood pressure measured by
the "tail cuff" method and platelet aggregation were not altered by either of the
ACE-Is. The antithrombotic activity of CAP was reduced by indomethacin (2.5
mg/kg, s.c.) and independently by the NO-synthase inhibitor N(G)-nitro L-arginine
methyl ester (3 mg/kg i.v. bolus + 3 mg/kg/h i.v. infusion, L-NAME). In the
latter case CAP regained its antithrombotic properties in rats pretreated with L
Arginine (300 mg/kg i.v. + 300 mg/kg/h i.v.) before administration of L-NAME
(p<0.05 vs. control). Moreover, the concomitant administration of indomethacin
and L-NAME failed to completely abolish the antithrombotic action of captopril.
Similar effects were observed in respect to the incidence of venous thrombosis.
Our study documents a novel and important effect of ACE-Is on the vein thrombotic
process and demonstrates the involvement of NO and PGI2 in this phenomenon.
PMID- 9657450
TI - Platelet dysfunction as the cause of spontaneous bleeding in two haemophilic
patients taking HIV protease inhibitors.
PMID- 9657451
TI - Prothrombin 20210A polymorphism and third generation oral contraceptives--a case
report of coeliac axis thrombosis and splenic infarction.
PMID- 9657452
TI - Protein C gene polymorphism and hypertensive cerebrovascular disease in Japanese.
PMID- 9657453
TI - On the release of von Willebrand factor from endothelial cells after venous
occlusion.
PMID- 9657454
TI - SimpliRED D-dimer assay: comparability of capillary and citrated venous whole
blood, between-assay variability, and performance of the test for exclusion of
deep vein thrombosis in symptomatic outpatients.
PMID- 9657455
TI - Monocyte tissue factor (CD142) and Mac-1 (CD11b) are increased in septic
patients.
PMID- 9657456
TI - Validation of predicted total body water and extracellular water by multi
frequency impedance in young Indonesian adults.
AB - To investigate the validity of the prediction of body water compartments by multi
frequency impedance in Indonesians, 42 adults (19 males and 23 females) were
recruited in Jakarta, the capital of Indonesia. Extracellular water (ECW) and
total body water (TBW) were measured with dilution techniques and predicted from
body impedance at 1 and 100 kHz, respectively, using prediction formulas
developed in a Dutch population. Furthermore, body weight, body height and body
density were measured and as a measure of body build TBW/height and ECW/height
were calculated. Percent ECW of body weight in both males (26 +/- 3%) and females
(23 +/- 2%) was higher compared to the Dutch reference population, and also the
body water distribution (ECW/TBW) was higher (0.46 +/- 0.04) compared to the
reference population. TBW/height and ECW/height appeared to be considerably lower
in the Indonesian group compared to the reference group, indicating a more
slender body shape. TBW was overestimated by 1.8 +/- 2.4 and 2.5 +/- 1.3 kg in
males and females, respectively. ECW was underestimated in males by 0.1 +/- 1.2
kg and slightly overestimated in females (0.1 +/- 1.0 kg). After corrections for
differences in body build and body water distribution the bias of the predicted
TBW was markedly reduced from 2.2 +/- 1.9 to 1.3 +/- 1.8 kg (males and females
combined). For ECW the bias after correction for body water distribution and body
build was 0.3 +/- 0.6 kg (males and females combined). It is concluded that multi
frequency impedance is suitable for the prediction of body water compartments at
the population level but, due to differences in body build and body water
distribution, validation in a larger group of Indonesian subjects is needed to
avoid systematic prediction errors.
PMID- 9657457
TI - Study design of a total reference diet for a population in Northern Italy.
AB - A market based of 91 food items was purchased in Northern Italy, based on a list
taken from a food survey previously conducted in the same area. The food items
from the survey were grouped into 14 categories. Food samples were collected,
homogenized, and frozen for the analysis of both the nutrient content and the
levels of mineral contaminants. The study design and decision processes behind
the choice of type and quantity of each food are explained. The relative
quantities of each food group were compared with those from two similar studies.
Finally, energy, nutrients, and mineral contaminants obtained by direct analysis
were compared with the calculations given on the food composition tables. The
comparison between the analyzed and calculated data only showed marked
differences in phosphorus, sodium, potassium, and copper intakes.
PMID- 9657458
TI - Fat sources in the Belgian diet.
AB - Food consumption data from the Belgian Interuniversity Research on Nutrition and
Health study (n = 11,302) were analyzed with regard to fat intake. Intakes of
macronutrients were compared between several subgroups in the population. The
major objective was to quantify the contribution of food groups and individual
food items to the intake of total fat, polyunsaturated (PUFA), monounsaturated
(MUFA) and saturated (SFA) fat in the Belgian diet. These results are compared to
nutritional guidelines and Italian, US and Dutch data. Major sources of fat are
butter (16% of the total intake) and baking margarine (8%). Major sources of SFA
are butter (24%) and cheese (8%), of MUFA butter (13%) and baking margarine (9%),
and of PUFA diet margarine (23%) and mayonnaise (11%).
PMID- 9657459
TI - Fatty acid composition of the Belgian diet: estimates derived from the Belgian
Interuniversity Research on Nutrition and Health.
AB - The major objective of this study was to determine the fatty acid composition of
the Belgian diet. Food consumption data from a large representative sample (n =
11,302) of the Belgian population between 25 and 74 years of age (BIRNH study)
were analyzed with regard to the intake of fatty acids. The fatty acid
composition of the major fat sources in the Belgian diet was determined and used
to calculate average intakes for fatty acids from C4 to C22. In addition, results
are compared to other studies and to guidelines for n-3 and n-6 fatty acids.
Saturated fatty acids provide 17% of the energy intake in the Belgian diet,
polyunsaturated fatty acids 7%, and monounsaturated fatty acids 14%. The intake
of total n-6 fatty acids is very high (6 en%), particularly of linoleic acid. The
intake of n-3 fatty acids is low, only 0.8 en%, which results in a low ratio of n
3 to n-6 (0.15). The most important sources of n-6 and n-3 fatty acids are
margarine and meat, respectively.
PMID- 9657460
TI - Olive oil supplementation in healthy adults: effects in cell membrane fatty acid
composition and platelet function.
AB - Ten healthy volunteers were given a daily supplement of 30 g olive oil for 6
weeks in order to evaluate how it would affect cell membrane composition and
ultimately platelet function. Fasting blood and cheek cell samples were taken
before commencing the study, after 21 and 42 days of supplementation and also at
30 days after finishing the supplement (washout). C18:1n-9 was significantly
increased (p < 0.01) in platelet and cheek cell phospholipids. Erythrocytes were
not good markers for C18:1n-9 intake and no significant change was found in this
tissue. There was a small nonsignificant decrease in platelet phospholipid 20:4n
6 after the supplementation, in accordance with previously published results.
C18:1n-9 did not persist in platelet membranes after the volunteers stopped
consuming the olive oil supplement, but in erythrocytes a significant increase (p
< 0.05) was found after the washout period. None of these changes in fatty acid
composition in the different tissues were related to significant changes in serum
cholesterol-related variables or in clotting factors or adenosine diphosphate
induced platelet aggregation.
PMID- 9657461
TI - Influence of different fat emulsions with 10 or 20% MCT/LCT or LCT on
lipoproteins in plasma of patients after abdominal surgery.
AB - In patients after elective abdominal surgery, different fat emulsions were used
to compare their efficacy in total parenteral nutrition and in normalizing plasma
lipoprotein levels. In five different groups with 5 patients each, half of the
nonprotein calories were given as medium-chain triglycerides/long-chain
triglycerides (1:1) or as long-chain triglycerides alone in 10 or 20% fat
emulsions or as glucose alone in a control group for 7 days. After surgery, an
initial decrease of all plasma lipoprotein components was followed by a different
behavior of glyceride-glycerol, cholesterol, phospholipids, and apolipoproteins.
Glyceride-glycerol in very-low-density lipoproteins and high-density lipoproteins
is increasing during infusion of fat emulsions and decreasing during overnight
interruption of infusions. After the 7-day infusion period, there was no
significant difference in very-low-density lipoprotein glyceride-glycerol as
compared with the values before different infusions. Low-density lipoprotein
cholesterol is reaching and exceeding preoperative concentrations between the 4th
and the 7th day, most during infusion of 10% fat emulsion and especially due to
an increase of free cholesterol. High-density lipoprotein cholesterol and
apolipoprotein A-I reach preoperative levels during infusion of fat emulsions but
not with glucose alone. Higher than preoperative values are reached in
phospholipids with all fat infusions already on day 4. Abnormal lipoprotein X
occurred least with the medium-chain/long-chain triglyceride 20% fat-infusion.
This fat emulsion is suggested as having the best normalizing effect on plasma
lipoproteins and best tolerance in patients after surgery.
PMID- 9657462
TI - Hepatic glycogen and lactate handling in dietary obese rats.
AB - Hepatic balances for glucose and its precursor, lactate, were calculated by
measuring hepatic blood flows and the arteriovenous differences of these
metabolites in 2 groups of overweight rats: cafeteria diet-fed rats and post
cafeteria rats. Obese rats show abnormal hepatic glycogen handling, since they do
not mobilize all hepatic glycogen stores after 24-hour starvation, in a situation
in which a lower rate of hepatic glucose output and a higher capacity for lactate
uptake are attained. The important decrease (about 50%) in the hepatic blood
flows observed in post-cafeteria rats versus control rats was similar to that
caused by 24-hour starvation in control animals, suggesting that after withdrawal
of the cafeteria diet, the liver blood flow of the post-cafeteria rats was
adapted to the low-food intake in order to make better use of the energy
consumed. The results also suggest an increased efficiency of hepatic lactate
uptake in post-cafeteria rats.
PMID- 9657463
TI - Chronic disease: infectious cause?
PMID- 9657464
TI - Primary stenting in acute myocardial infarction: the promise and the proof.
PMID- 9657465
TI - Heparin responsiveness in vitro as a prognostic tool for vascular graft stenosis:
a tale of two cell types?
PMID- 9657466
TI - Dispersion of ventricular repolarization: reality? Illusion? Significance?
PMID- 9657467
TI - Reduced endothelial nitric oxide synthase expression and production in human
atherosclerosis.
AB - BACKGROUND: NO regulates vascular tone and structure, platelets, and monocytes.
NO is synthesized by endothelial NO synthase (eNOS). Endothelial dysfunction
occurs in atherosclerosis. METHODS AND RESULTS: With a porphyrinic microsensor,
NO release was measured in atherosclerotic human carotid arteries and normal
mammary arteries obtained during surgery. eNOS protein expression was analyzed by
immunohistochemistry. In normal arteries, the initial rate of NO release after
stimulation with calcium ionophore A23187 (10 micromol/L) was 0.42+/-0.05
(micromol/L)/s (n=10). In contrast, the initial rate of NO release was markedly
reduced in atherosclerotic segments, to 0.08+/-0.04 (micromol/L)/s (n=10,
P<0.0001). NO peak concentration in normal arteries was 0.9+/-0.09 micromol/L
(n=10) and in atherosclerotic segments, 0.1+/-0.03 micromol/L (n=10, P<0.0001).
Reduced NO release in atherosclerotic segments was accompanied by marked
reduction of immunoreactive eNOS in luminal endothelial cells, although specific
endothelial cell markers (CD31) were present (n=13). Endothelial cells of vasa
vasorum of atherosclerotic segments, however, remained positive for eNOS, as was
the endothelium of normal arteries. CONCLUSIONS: In clinically relevant human
atherosclerosis, eNOS protein expression and NO release are markedly reduced.
This may be involved in the progression of atherosclerosis.
PMID- 9657468
TI - Effects of tumor necrosis factor gene polymorphisms on patients with congestive
heart failure. VEST Investigators for TNF Genotype Analysis. Vesnarinone Survival
Trial.
AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known to be elevated in
patients with congestive heart failure (CHF). Two biallelic polymorphisms have
been identified in the TNF gene locus: one in the promoter region of TNF-alpha
(TNFA1/2), and the other in the first intron of TNF-beta (TNFB1/2). Both TNFA2
and TNFB2 alleles are associated with high TNF-alpha production in vitro and
susceptibility to inflammatory diseases. Given the importance of TNF-alpha in the
pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF
patients and the correlation of genotypes to in vivo TNF-alpha levels. METHODS
AND RESULTS: TNFA and TNFB genotypes were determined by the polymerase chain
reaction-restriction fragment length polymorphism technique. There were no
differences in the TNF allele frequencies between CHF (n=229; TNFA1/2=0.84/0.16,
TNFB1/2=0.33/0.67) and control subjects (n=139; TNFA1/2=0.84/0.16,
TNFB1/2=0.32/0.68). In 211 patients with CHF, circulating levels of TNF-alpha and
the soluble receptors type I and type II were measured by ELISA: 6.18+/-3.59
pg/mL, 1768+/-761 pg/mL, and 4484+/-1750 pg/mL, respectively. There were no
correlations between TNFA or TNFB genotypes and circulating levels of TNF-alpha
or its soluble receptors in the CHF patients. CONCLUSIONS: Despite their
association with other inflammatory diseases, neither TNFA nor TNFB polymorphisms
are related to the presence of CHF or the elevation of circulating TNF-alpha.
Thus, other factors may be more important in determining the circulating levels
of TNF-alpha in CHF.
PMID- 9657469
TI - Randomized comparison of coronary stenting with balloon angioplasty in selected
patients with acute myocardial infarction.
AB - BACKGROUND: Although the benefits of primary angioplasty in acute myocardial
infarction have been demonstrated, several areas for improvement remain.
Therefore, a prospective randomized trial comparing primary stenting with balloon
angioplasty in patients with acute myocardial infarction was conducted. METHODS
AND RESULTS: Patients with acute myocardial infarction were randomly assigned to
undergo either primary stenting (n=112) or balloon angioplasty (n=115). The
clinical end points were death, recurrent infarction, subsequent bypass surgery,
or repeat angioplasty of the infarct-related vessel. The overall mortality rate
at 6 months was 2%. Recurrent infarction occurred in 8 patients (7%) after
balloon angioplasty and in 1 (1%) after stenting (P=0.036). Subsequent target
vessel revascularization was necessary in 19 (17%) and 4 (4%) patients,
respectively (P=0.0016). The cardiac event-free survival rate in the stent group
was significantly higher than in the balloon angioplasty group (95% versus 80%;
P=0.012). CONCLUSIONS: In selected patients with acute myocardial infarction,
primary stenting can be applied safely and effectively, resulting in a lower
incidence of recurrent infarction and a significant reduction in the need for
subsequent target-vessel revascularization compared with balloon angioplasty.
PMID- 9657470
TI - Vein graft stenosis and the heparin responsiveness of human vascular smooth
muscle cells.
AB - BACKGROUND: Vascular smooth muscle cell (VMSC) proliferation is an essential
component of myointimal hyperplasia, which is implicated in the failure of 30% to
50% of vascular interventions, such as coronary angioplasty and peripheral vein
grafting. We have shown that cells derived from stenotic lesions in infrainguinal
vein grafts were significantly more resistant than controls to growth inhibition
by heparin. METHODS AND RESULTS: In a prospective study, we correlated
antiproliferative responses to heparin in vitro with graft patency after 1 year.
Sixty-two patients with infrainguinal vein grafts were entered into a graft
surveillance program for > or = 1 year. At operation, saphenous vein segments
were explanted for VSMC culture. Cell proliferation in response to fetal calf
serum was later determined in the presence and absence of heparin. In 35 cell
cultures, including 13 from the above-mentioned patients, [3H]heparin binding was
also estimated. VSMCs from patients with patent grafts were significantly more
sensitive to growth inhibition by heparin than cells from patients with stenoses
(median, 54% versus 20.9%, P<0.001), and [3H]heparin binding was strongly
correlated with inhibition of proliferation (r=0.81). CONCLUSIONS: Responsiveness
to heparin in cultured VSMCs is a strong predictor of outcome for infrainguinal
vein grafts, and reduced sensitivity to heparin is correlated with decreased
heparin binding. Relative resistance to the antiproliferative action of heparin
may be a marker for aberrant regulation of VSMC growth.
PMID- 9657471
TI - Lower expression of neutrophil adhesion molecule indicates less vessel wall
injury and might explain lower restenosis rate after cutting balloon angioplasty.
AB - BACKGROUND: The Cutting Balloon is a novel dilatation catheter for coronary
angioplasty (InterVentional Technologies Inc). It produces longitudinal,
microsurgical incisions in the vessel wall before the actual dilatation. It is
assumed that these controlled surgical incisions relieve hoop stress and reduce
vessel wall injury and eventually restenosis. However, no clinical indicator to
support the theory of reduced injury has been described. Certain clusters of
differentiation (eg, CD11, CD18 on the leukocytes) are implicated in leukocyte
adhesion, increased permeability, and opsonization. Therefore, they might serve
as clinical indicators of the injury level of the vessels after angioplasty.
METHODS AND RESULTS: We randomly selected 64 patients with isolated left anterior
descending coronary artery disease for either Cutting Balloon angioplasty or
conventional balloon angioplasty. The expression of CD18 and CD11b on the surface
of neutrophils was determined by flow cytometric analysis. Serum levels of
soluble intercellular adhesion molecule-1 (sICAM-1) were also measured. The
expression of both the CD18 and CD11b in the coronary sinus blood gradually
increased and reached its maximum at 48 hours after angioplasty. The sICAM-1
levels in the coronary sinus serum also increased after angioplasty. Percentage
increases of CD18 and CD11b expression and the increase of the sICAM-1 levels at
48 hours after angioplasty (as ratios to baseline values before angioplasty) were
less in the Cutting Balloon angioplasty group than in the conventional balloon
angioplasty group (CD18, 1.10+/-0.05 versus 1.31+/-0.05, P<0.05; CD11b, 1.23+/
0.06 versus 1.72+/-0.10, P<0.001; sICAM-1, 1.12+/-0.05 versus 1.25+/-0.02,
P<0.05). In all patients, the late lumen loss at follow-up angiogram positively
correlated with the increased levels of CD11b (R=0.59, P<0.001) and sICAM-1
(R=0.38, P<0.05) at 48 hours after angioplasty. CONCLUSIONS: Balloon angioplasty
upregulated Mac-1 (CD11b/CD18) on the surface of the neutrophils and increased
sICAM-1 levels in association with late loss increase. These changes were
significantly smaller in the Cutting Balloon angioplasty group than in the
conventional balloon angioplasty group. This suggests that Cutting Balloon
angioplasty may produce less vessel wall injury and, consequently, less
neutrophil activation, which may account for the lower rate of restenosis.
PMID- 9657472
TI - Association of remnant lipoprotein levels with impairment of endothelium
dependent vasomotor function in human coronary arteries.
AB - BACKGROUND: It remains undetermined whether triglyceride-rich lipoproteins are an
independent risk factor for atherosclerosis. METHODS AND RESULTS: The correlation
of responses of coronary arterial diameter (quantitative coronary angiography)
and coronary blood flow (intracoronary flow wire technique) to intracoronary
infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors
including remnant lipoprotein levels was statistically analyzed in 106
consecutive subjects with normal coronary angiograms. Remnant lipoproteins were
isolated from fasting blood with an immunoaffinity mixed gel containing anti
apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate
stepwise regression analysis, remnant lipoprotein levels had the most significant
correlation with abnormal epicardial coronary vasomotor responses to
acetylcholine infusion, reflected by impaired dilation or constriction of the
epicardial coronary arteries, and the levels also had an inverse and independent
correlation with the coronary blood flow increase in response to acetylcholine.
In a subgroup of 53 consecutive subjects, constrictor responses of epicardial
coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50
micromol/min for 4 minutes) at baseline, reflecting the presence of coronary
nitric oxide bioactivity, had an inverse and independent correlation with remnant
lipoprotein levels by use of multivariate analysis. CONCLUSIONS: Remnant
lipoprotein levels were independently associated with abnormal endothelium
dependent vasomotor function in large and resistance coronary arteries in humans,
indicating that remnant lipoproteins may impair endothelial vasomotor function in
human coronary arteries. The decrease in coronary nitric oxide bioactivity may be
responsible in part for the inhibitory effects of remnant lipoproteins.
PMID- 9657473
TI - Marked reduction in internal atrial defibrillation thresholds with dual-current
pathways and sequential shocks in humans.
AB - BACKGROUND: This study tested the ability of sequential shocks delivered through
dual-current pathways to lower the atrial defibrillation threshold (ADFT)
compared with a biphasic shock through a standard single-current pathway. METHODS
AND RESULTS: Electrodes were positioned in the right atrial appendage (RA), left
subclavian vein (LSV), proximal coronary sinus (CSos), and distal coronary sinus
(DCS) in 14 patients with chronic atrial fibrillation (170+/-185 days). Using a
step-up protocol, we compared ADFTs for a single-current pathway (RA-->DCS) that
used a single 7.5/2.5-ms biphasic shock from a 150-microF capacitor with those
for a dual-current pathway system (RA-->DCS followed by CSos-->LSV) using
sequential 7.5/2.5-ms biphasic shocks with capacitor discharge waveforms for 150
microF and 600-microF capacitors. Both dual-current pathway configurations (2.0+/
0.4 J for 150-microF capacitance, 2.4+/-0.5 J for 600-microF capacitance) had a
significantly lower ADFT than the single-current pathway (5.1+/-1.8 J). Whereas
the dual-current pathway with 150-microF capacitor shocks had a significantly
lower energy threshold, there was no statistical difference in terms of leading
edge voltage compared with the dual-current pathway with 600-microF capacitance
shocks. There were no ventricular arrhythmias induced with appropriately
synchronized shocks. CONCLUSIONS: For internal atrial defibrillation in humans,
sequential biphasic waveforms delivered over dual-current pathways resulted in a
markedly reduced (>50% reduction) ADFT compared with a single shock over a single
current pathway.
PMID- 9657474
TI - 31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients
with hypertrophic cardiomyopathy.
AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected
death in adolescents and young adults. Alterations in myocardial metabolism are
considered to be causes for contractile dysfunction. We examined the question of
whether metabolic abnormalities antedate the manifestation of symptoms in
patients with HCM. METHODS AND RESULTS: Proton-decoupled 31P NMR spectroscopy of
the anterior left ventricular wall of the heart of 14 young, asymptomatic
patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the
phosphate metabolites were compared with those of normal control subjects. The
patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine
(PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11
normal control subjects. In addition, the group of patients with severe
hypertrophy of the interventricular septum (n=8) showed a significantly increased
(P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in
control subjects. Both abnormalities are similar to those found in ischemic
myocardium. This view is also supported by a significantly increased (P<0.01)
phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared
with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism.
CONCLUSIONS: 31P NMR spectroscopy detects alterations of myocardial metabolism in
asymptomatic patients with HCM. These alterations may contribute to the
understanding of the pathophysiology and natural history of the disease.
PMID- 9657475
TI - Assessment of QT dispersion for prediction of mortality or arrhythmic events
after myocardial infarction: results of a prospective, long-term follow-up study.
AB - BACKGROUND: Risk stratification by means of analysis of QT dispersion (QTD) in
the 12-lead surface ECG is under intense investigation in various patient
populations. The aim of the present prospective study was to evaluate the
prognostic value of QTD and other ECG variables reflecting dispersion of
ventricular repolarization in comparison with established risk stratifiers during
long-term follow-up in a large cohort of post-myocardial infarction patients
treated according to contemporary therapeutic guidelines. METHODS AND RESULTS: In
280 consecutive infarct survivors, the 12-lead ECG was optically scanned and
digitized for analysis of QTD (QTmax-QTmin) and 25 other repolarization
variables, including recently developed and validated parameters such as the T
peak-to-T end interval and the area under the T wave. In addition, a variety of
established risk stratifiers were assessed. After a mean follow-up period of 32+/
10 months, 30 patients reached one of the prospectively defined study end points
(death, ventricular tachycardia, or resuscitated ventricular fibrillation).
Comparisons between event and nonevent patients by means of Kaplan-Meier event
probability analyses revealed that none of the ECG dispersion variables were of
discriminative value. In contrast, variables such as left ventricular ejection
fraction (P=0.007), mean 24-hour heart rate (P=0.022), or heart rate variability
(P=0.007) proved to be potentially useful risk stratifiers in this patient
population. On multivariate analysis, only LVEF, heart rate variability, and a
history of thrombolysis were independent predictors of outcome. CONCLUSIONS:
Determination of QTD from the surface ECG even when performed with the best
available methodology failed to predict subsequent risk in this large series of
infarct survivors.
PMID- 9657476
TI - Selective ET(A) receptor antagonism reduces neointimal hyperplasia in a porcine
coronary stent model.
AB - BACKGROUND: As endothelin binds to ET(A) receptors, it stimulates vascular smooth
muscle cell proliferation and may thus be pivotally involved in the pathogenesis
of restenosis. This study assessed the ability of a potent and selective ET(A)
antagonist to reduce neointimal hyperplasia in a porcine coronary artery stented
injury model. METHODS AND RESULTS: Fifty-five pigs were randomized to receive
placebo or the oral ET(A)-selective antagonist ABT147627 twice daily for 28 days
in one of three doses: 0.75 mg/kg (low), 3.75 mg/kg (mid), and 10.0 mg/kg (high).
Each underwent oversized stent deployment in two randomly assigned major
epicardial coronary arteries. Three animals (5.5%) died as a consequence of stent
thrombosis within 24 hours of the procedure. The remaining 52 animals (13 pigs
per group) survived without complication until predetermined euthanasia at 28
days. In the placebo group, mean injury score was 1.73+/-0.80, with a mean
neointimal response of 0.45+/-0.24 mm. By comparison, the low-dose group had a
similar mean injury score of 1.79+/-0.75 with reduced neointimal response, 0.36+/
0.22 mm (P<0.01). Mean injury score in the mid-dose animals was significantly
greater than in the placebo group (1.94+/-0.92; P<0.05). The neointimal
hyperplasia associated with this injury was less than with placebo, although the
difference did not reach statistical significance (0.40+/-0.25 mm; P=0.05). In
the high-dose pigs, mean injury score was also significantly greater than in the
placebo arm (1.93+/-0.73; P<0.05). Despite this, neointimal response was also
significantly less (0.37+/-0.37 mm; P<0.01). CONCLUSIONS: Oral, selective ET(A)
receptor antagonism significantly reduced neointimal hyperplasia forming over
porcine coronary stented injuries in the first 28 days. This strategy may have
clinical potential for the limitation and treatment of coronary restenosis after
percutaneous revascularization.
PMID- 9657477
TI - 99mTc-HL91: "hot spot" detection of ischemic myocardium in vivo by gamma camera
imaging.
AB - BACKGROUND: 99mTc-HL91 is a new hypoxia imaging agent that demonstrates increased
uptake and retention in globally hypoxic myocardium in vitro. The purpose of this
study was to determine whether 99mTc-HL91 could detect regional ischemia in vivo
by gamma camera imaging. METHODS AND RESULTS: Eight open-chest dogs with left
circumflex (LCx) stenoses were studied. Injection of 5 mCi of 99mTc-HL91 and
microspheres was followed by imaging over 4 hours. Heart slices were imaged, then
stained with triphenyltetrazolium chloride (TTC), and tissues were well-counted.
TTC staining demonstrated no injury. Mean LCx blood flow was 0.32+/-0.04 mL x
min(-1) x g(-1), and mean left anterior descending coronary artery (LAD) flow was
0.96+/-0.02 mL x min(-1) x g(-1) (ratio, 0.33). "Hot spots" were detected in 8 of
8 experiments in vivo within 60 minutes and improved over 4 hours. Region of
interest analysis of LCx/LAD activity ratios demonstrated significant increases
within 30 minutes (final ratio, 3.0; P<0.05). LCx and LAD washout curves
demonstrated significant differences within 15 minutes. Washout curves were
biexponential over 1 hour, followed by linear retention from 1 to 4 hours. Four
hour fractional retention was 0.12 for LAD and 0.44 for LCx (P<0.01). Myocardial
flow versus tracer uptake demonstrated 2 phases: phase 1 (flow, 0.05 to 0.7 mL x
min(-1) x g(-1)) had an inverse linear correlation (r= -0.80); phase 2, (flow,
>0.7 mL x min(-1) x g(-1)) had no correlation. Ischemic heart/liver ratios
remained near 1.0 for 4 hours. CONCLUSIONS: 99mTc-HL91 positively identifies
regional myocardial ischemia in a canine model using 99mTc imaging. Quantitative
techniques allowed identification of ischemic myocardium within 15 minutes of
tracer administration.
PMID- 9657478
TI - Postrepolarization refractoriness versus conduction slowing caused by class I
antiarrhythmic drugs: antiarrhythmic and proarrhythmic effects.
AB - BACKGROUND: Conduction block may be both antiarrhythmic and proarrhythmic. Drug
induced postrepolarization refractoriness (PRR) may prevent premature excitation
and tachyarrhythmia induction. The effects of propafenone and procainamide on
these parameters, and their antiarrhythmic or proarrhythmic consequences, were
investigated. METHODS AND RESULTS: In 11 isolated Langendorff-perfused rabbit
hearts, monophasic action potentials (MAPs) were recorded simultaneously from six
to seven different right and left ventricular sites, along with a volume
conducted ECG. All recordings were used to discern ventricular tachycardia (VT)
or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5)
or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of
procainamide (20 micromol/L) or propafenone (1 micromol/L) to the perfusate. MAPs
were analyzed for action potential duration at 90% repolarization (APD90),
conduction times (CT) between the pacing site and the other MAPs, and PRR
(effective refractory period-APD90=PRR) and related to the induction of VT or VF.
During steady-state pacing, procainamide and propafenone prolonged APD90 by 12%
and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing,
whereas propafenone slowed mean CT by up to 400% (P<0.001 versus baseline and
procainamide). Wavelength was not changed significantly by procainamide but was
shortened fourfold by propafenone at S5. Both drugs produced PRR, which was
associated with a 70% decrease in VF inducibility with procainamide and
elimination of VF with propafenone. Despite this protection from VF, monomorphic
VT was induced with propafenone in 57% of burst stimulations. CONCLUSIONS: Drug
induced PRR protects against VF induction. Propafenone promotes slow monomorphic
VT, probably by use-dependent conduction slowing and wavelength shortening.
PMID- 9657479
TI - Images in cardiovascular medicine. Simultaneous morphological and functional
assessment of a renal artery stent intervention with intravascular ultrasound.
PMID- 9657480
TI - Images in cardiovascular medicine. Metabolic imaging identifies non-Hodgkin's
lymphoma infiltrating heart.
PMID- 9657481
TI - Diagnosing essential fatty acid deficiency.
PMID- 9657482
TI - Predictive value of EBCT scanning.
PMID- 9657483
TI - Testing the efficacy of lipid-lowering therapy versus revascularization: the time
has come, or is it past due?
PMID- 9657484
TI - Coronary calcium, subsequent events, and selection bias.
PMID- 9657485
TI - Lipoprotein lipase gene variants and coronary risk.
PMID- 9657486
TI - Symptomatic lumbar spinal stenosis.
PMID- 9657487
TI - Anterior lumbosacral dislocation: case report and review of the literature.
AB - BACKGROUND: Anterior lumbosacral dislocation is a rare traumatic anterior
spondylolisthesis. METHODS: We report a new case surgically treated and review
the eight cases previously reported. RESULTS: The mechanism of injury is
hyperflexion-distraction. Neurological signs are inconsistent. Indirect
radiological signs such as bilateral multiple transverse process fractures are
strongly suggestive of the diagnosis. This complete soft tissue injury induces a
definitive instability and requires an open reduction with posterior fixation.
CONCLUSIONS: Suspicion of lumbosacral dislocation requires a computed tomography
scan exploration with multiplanar reconstructions. Early reduction is associated
with neurologic recovery. However, prognosis is correlated with the initial
neurologic status and the severity of other associated injuries.
PMID- 9657488
TI - Pain and the spine.
PMID- 9657489
TI - Neuropsychological results of craniopharyngioma surgery in adults: a prospective
study.
AB - BACKGROUND: The optimal management of craniopharyngiomas is a topic of ongoing
debate. Supporters of limited surgery for craniopharyngiomas claim that more
radical approaches are afflicted with adverse neuropsychological sequelae. Since
prospective studies on this issue have not yet been performed, we assessed
neuropsychological functioning in adults before and after craniopharyngioma
surgery. METHODS: Thirteen adults with an age range of 17-76 years (mean, 45
years) were included in the study. Surgery included a transcranial procedure in
10 patients. The bifrontal interhemispheric approach predominated (n = 7).
Neuropsychological evaluation was performed before and 3 months after surgery.
The test battery was adjusted to evaluate function related to structures in the
operative trajectory and at the tumor site. RESULTS: A complete tumor removal was
accomplished in eight patients and subtotal removal in three patients. IQ scores
for verbal intelligence were in the normal range and not affected by surgery
(mean IQ score preoperative: 106.8; postoperative 107.4). In 12 of 13 patients,
immediate recall, delayed recall and recognition memory were not impaired after
surgery. Postoperative results for abstract thinking were in the normal or above
normal range. Cognitive speed was impaired in three patients preoperatively and
in two patients postoperatively. Overall results were significantly better after
surgery. Word fluency was not affected by surgery. Quality of life for the
category "sleep" was impaired preoperatively, and this improved after surgery.
Otherwise, quality of life was normal both before and after surgery. CONCLUSIONS:
Neuropsychological performance and quality of life are generally not impaired
after surgical removal of craniopharyngiomas. The findings support the attitude
that the initial therapy of craniopharyngiomas should be an attempt at total
removal.
PMID- 9657490
TI - Large and invasive silent corticotroph-cell adenoma with elevated serum ACTH: a
case report.
AB - BACKGROUND: A silent corticotroph-cell adenoma (SCCA) is defined as evidence of
immunoreactive ACTH in tumor cells of a pituitary adenoma that is not associated
with symptoms of Cushing's disease. Most previous reports have discussed the
etiology of this unique entity; however, the precise mechanisms of its "silence"
are not clear yet. We discuss the pitfalls of endocrinological diagnosis and
surgical management of SCCA. METHODS: A 63-year-old man, without the symptoms of
Cushing's disease, demonstrated elevated serum levels of ACTH, but normal levels
of cortisol. ACTH was measured by newly developed immunoradiometric assays (RMA),
which are more specific for biologically active ACTH than conventional
radioimmunoassay (RIA). The tumor was more than 3 cm in diameter and invaded both
the cavernous sinus and the sphenoid sinus. RESULTS: Two different types of IRMAs
revealed elevated serum ACTH levels. The tumor was removed successfully by staged
operations. The high levels of serum ACTH were normalized after the second
operation. CONCLUSION: The cause of the silence of SCCA is not clear yet. The
elevated serum ACTH levels in the present case were not attributable to "Big
ACTH." We suggest one possibility: the cause of the silence might be a minor
variant of ACTH, detected by IRMA, leading to less biological activity of ACTH.
This type of adenoma is invasive in nature and can potentially grow large because
it is free of endocrinological symptoms. We emphasize the appropriate surgical
strategy to normalize the serum levels of ACTH in case of SCCA.
PMID- 9657491
TI - High-power diode laser in neurosurgery: clinical experience in 30 cases.
AB - BACKGROUND: High-power semiconductor diode lasers were recently introduced and
have been tested in ophthalmology and general surgery. These lasers are
attractive from the practical and economical standpoint, and have enough power to
perform most surgical procedures. They could replace other surgical lasers such
as CO2, argon, 1.06 microm, and 1.32 microm Nd-YAG lasers for many applications
in neurosurgery. We report our initial experience with the first available 0.805
microm surgical diode laser, the Diomed 25 (Diomed, Ltd, Cambridge, U.K.) in a
series of 30 patients. METHODS: The diode laser was evaluated during surgical
resection of various types of central nervous system tumors in 30 patients. It
was used free-hand in 27 patients in contact and non-contact, continuous wave
(cw) and pulsed modes, and during ventricular endoscopy in three patients.
Average time of laser use during a procedure was 248 seconds. Output power ranged
from 1 to 25 watts, with an average power per patient of 2.64 to 15.5 watts
(mean, 8.78 watts). Total energy delivered ranged from 65 to 11,051 joules per
patient. RESULTS: Using 600- or 400-microm non-contact optic fiber, well
pigmented tumor tissue hemostasis was obtained at cw 3 to 10 watts with a
defocused beam, whereas vaporization required 10-25 cw or pulsed watts with a
focused beam. Soft and tough tissue section could be obtained using a sculpted
cone-shaped (600-300 microm tip) contact fiber at 7-10 cw watts after fiber tip
charring. Because of the deeper penetration of 0.805-microm light in non
pigmented tissues, non-contact mode is not recommended for white matter or poorly
vascularized tumors. The contact mode was not efficient on very soft tissues such
as edematous brain parenchyma. The contact fibers proved to be very fragile
because of heat generation. CONCLUSIONS: The high power diode laser proved to be
efficient for hemostasis, section and vaporization, using contact and non-contact
modes, at different output powers. Economical and ergonomical advantages of this
new generation of surgical lasers may cause them to replace other surgical lasers
such as argon, CO2, and Nd-YAG lasers, mostly for tumor surgery.
PMID- 9657492
TI - Development of a fluorescein operative microscope for use during malignant glioma
surgery: a technical note and preliminary report.
AB - BACKGROUND: Fluorescein has been used in the field of neurosurgery; however,
fluorescein enhancement or contrast proved to be inadequate because of a lack of
appropriate light sources or filters. A new operative microscope system, in which
the microscope itself is equipped with excitation and barrier filters, and the
application of this system to surgery for malignant glioma are reported. METHODS:
BP 450-490, a glass interference filter used as the excitation filter for the
light source optical system, and a Kodak Wratten No. 12 filter used as the
barrier filter for the microscope optical system, were incorporated in the
operative microscope. A switching apparatus was devised so that filters could be
inserted instantly when fluorescence was to be observed. Ten cases in which the
location of malignant glioma was enhanced by computed tomography (CT) or magnetic
resonance imaging (MRI) were selected for this study. After incision of the dura
mater, 8 mg/Kg body weight of fluorescein Na was injected intravenously. Tumor
removal was begun some 20 min after the injection with the aid of this newly
developed fluorescein operative microscope system. RESULTS: Fluorescence
enhancement and contrast were remarkable when this system was used. It enabled
surgical maneuvering while viewing the fluorescent image of objects. The
boundaries between the tumor areas enhanced by CT or MRI and the surrounding
brain could be clearly distinguished in the fluorescent image; the tumor was
totally removed, except for deep lesions, without any neurological deterioration.
When the tumor was relatively hard, the area surrounding the tumor was aspirated
with a cavitron ultrasonic surgical aspirator; as a result, the tumor could be
removed en bloc; otherwise, the fluorescent tumor was removed piece by piece.
CONCLUSIONS: This system provides adequate fluorescent enhancement and contrast
and is useful for observing intravenously injected fluorescein during an
operation. Though long-term follow-up of such cases is needed, the conditions of
our patients immediately after surgery for malignant glioma were satisfactory.
These results suggest that our fluorescein operative microscope system is highly
effective in surgery for malignant glioma.
PMID- 9657493
TI - Spiral CT scanning in the detection and evaluation of aneurysms of the Circle of
Willis.
AB - PURPOSE: To assess the utility of spiral computed tomography (CT) with three
dimensional reconstruction in defining aneurysms of the Circle of Willis.
METHODS: Eighty-one patients with angiographic or surgical correlation were
studied between 1993 and 1995, with surface rendered reconstructions of the
arteries of the Circle of Willis. RESULTS: Spiral CT was useful in six clinical
situations: further assessment in cases with CT suspicion of an aneurysm, follow
up of known untreated aneurysms or aneurysm remnants, subarachnoid hemorrhage
(SAH) with negative angiography, a past or family history of aneurysms, and
improved definition of aneurysm anatomy. Ten of fifteen patients with previous
surgery had no significant artifacts on the spiral study. In 66 other patients
studied in search of aneurysms, the sensitivity of detection was 95% and
specificity 74%. Seventeen of nineteen aneurysms 3 mm or less in size and 38 of
39 larger were detected by spiral CT. Four of thirteen patients with SAH and
previous negative angiography had aneurysms identified, which were confirmed at
surgery. CONCLUSIONS: There is great promise in the use of spiral CT in
demonstrating aneurysms of the Circle of Willis, including very small ones.
Careful detailing of scan protocols and meticulous examination of multiplanar
images are needed for maximum accuracy.
PMID- 9657494
TI - Magnetic resonance angiographic source images for depicting topography and
surgical planning for middle cerebral artery aneurysms: technique application.
AB - PURPOSE: To evaluate the usefulness of magnetic resonance (MR) angiographic
source images for determining the feasibility of M1 segment control via the
distal approach in pterional craniotomy for middle cerebral artery (MCA)
aneurysms. METHODS: MR angiographic source and conventional angiographic source
images were obtained in 40 patients with MCA aneurysms. Each aneurysm was treated
surgically using a pterional craniotomy. We initially approached the aneurysm
distally. When this was judged inappropriate, the approach was altered to
proximally. We compared the topography based on these angiograms to that
confirmed during surgery. RESULTS: MR angiographic source images visualized the
aneurysm, the M1 and M2 segments of the MCA, the insula, and the frontal and
temporal opercula in all 40 patients. In 22 (55%) of them, the distal portion of
the M1 segment was recognized from the posterolateral perspective between the
aneurysmal neck and the insular surface. These aneurysms were successfully
clipped via the distal approach after definite proximal control of the MCA was
obtained. CONCLUSIONS: It was concluded that MR angiographic source images have a
distinguishing feature in defining cerebral tissue-vascular relationships and
that they are useful in the surgical planning for MCA aneurysms.
PMID- 9657495
TI - Nuclear multiparameter flow cytometric DNA analysis of human brain tumors:
correlation of DNA content with tumor histology and clinical behavior.
AB - BACKGROUND: Using fresh surgical specimens of brain tumors to investigate
cellular DNA content is uncommon. The aim of this study is to elucidate the
relationship among cellular nuclear DNA content, tumor histology, and tumor
clinical behavior of various tumors of the central nervous system. METHODS:
Multiparameter flow cytometry (FACStar, Becton-Dickinson, San Jose, CA) was
randomly applied to analyze 40 fresh surgical specimens from brain tumors.
Histologically, there were 19 cases of benign tumors and 21 cases of malignant
tumors. RESULTS: DNA distribution profiles in the benign tumors revealed 15 cases
of diploidy and four cases of aneuploidy, while the malignant tumors had eight
cases of diploidy and 13 cases of aneuploidy (p < 0.01). The mean DNA index (DI)
in benign tumors was 1.13 +/- 0.27 and in malignant tumors 1.43 +/- 0.48 (p <
0.05). The mean proliferative index (PI) in benign tumors was 10.27 +/- 5.46% and
18.44 +/- 8.98% in malignant tumors (p < 0.05). Clinically, 10 patients had
postoperative recurrence. The PI in recurrent and nonrecurrent tumors was 17.83
+/- 11.13% and 13.20 +/- 7.19%, respectively (p < 0.05). The 1-year cumulative
survival rate in benign tumors was 78.9%, and 57.1% in malignant tumors (p <
0.05). CONCLUSIONS: Malignant tumors had a significantly higher incidence of
aneuploid DNA histograms, a higher DNA index, and a higher proliferative index.
Tumors with a high PI had a higher incidence of recurrence and a lower survival
rate. Multiparameter DNA analysis by flow cytometry provides a valuable
diagnostic aid for the histopathologic differentiation of human brain tumors.
PMID- 9657496
TI - Surgical treatment of benign intracranial hypertension--subtemporal decompression
revisited.
AB - BACKGROUND: Subtemporal decompression, first advocated by Dandy for the treatment
of benign intracranial hypertension or pseudotumor cerebri, has been replaced as
a treatment mainstay by medical management using diuretics, steroids, and lumbar
puncture. Failure of these forms of treatment has frequently led to insertion of
cerebrospinal fluid shunts. METHODS: We have retrospectively reviewed the long
term outcome of eight patients who were treated by subtemporal decompression
(STD) for classical presentations of refractory benign intracranial hypertension.
The follow-up period ranged from 8 to 26 years. RESULTS: Within 1 month of STD,
deterioration in visual fields and acuity resolved in all eight patients. Five of
eight patients required CSF diversion procedures after subtemporal decompression
to control headaches. No patient experienced recurrent permanent visual
deterioration after STD. CONCLUSION: STD may be the most effective treatment in
both long and short term follow-up to provide lasting relief and prevention of
visual morbidity caused by refractory benign intracranial hypertension.
PMID- 9657497
TI - Continuous external CSF drainage--a perpetual problem in neurosurgery.
AB - BACKGROUND: Continuous external CSF drainage represents a well established
procedure which has been improved by many technical contributions. We present our
experience in a prospective study of 212 needle trephinations in 165 consecutive
patients with a new screw fixation device. METHODS: The entire procedure is
performed at the bedside under local anesthesia with a twist drill. The
trephination needle is inserted into the self-tapping cannulated screw fixed to
the skull. RESULTS: The mean operation time was 6 min, and the duration of
ventricular drainage ranged from 2 h to 44 days. Ninety-one percent (N = 193) of
ventricular needles in our series were placed at the first targeting attempt. ICP
monitoring and -therapy (88%) were the main indications for needle trephination
in our study. During the study period we observed needle associated
complications, such as intracerebral hemorrhages (N = 2, 1%) and infections (N =
17, 8%). CONCLUSIONS: Concerning infection, primary insufficient fixation, and
general surgical handling, we found a clear learning curve during the course of
our study. In spite of the initial problems at the time of introduction we have
to emphasize the outstanding advantages of the new ventriculostomy device: It is
a time-saving bedside procedure equipped with an optimum fixation device and it
enables uncomplicated exchange of the needle in case of obstruction.
PMID- 9657498
TI - Neurosurgery of the peripheral nervous system: cubital tunnel syndrome.
PMID- 9657499
TI - Differentiating external hydrocephalus from chronic subdural hematoma.
PMID- 9657500
TI - Advice to young neurosurgeons.
PMID- 9657501
TI - What kind of business is medicine--from a business perspective?
PMID- 9657502
TI - Strategic planning for neurosurgeons.
PMID- 9657503
TI - Tuberculosis: where do we stand?
PMID- 9657504
TI - An investigation into the interaction between drug efficacy and drug price of
praziquantel in determining the cost-effectiveness of school-targeted treatment
for Schistosoma mansoni using a population dynamic model.
AB - A population dynamic model of schistosome transmission was used to investigate
the interaction between drug efficacy and drug price of different brands of
praziquantel in determining the cost-effectiveness of school-targeted treatment
for Schistosoma mansoni. In this analysis, costs were affected by coverage, drug
price and distance travelled, and effectiveness by coverage and drug efficacy.
Four effectiveness measures were assessed: the number of infection case-years
prevented, heavy infection case-years prevented, hepatomegaly case-years
prevented and fibrosis case-years prevented. The interactions between drug
efficacy and drug price were complex. In particular, there was a highly nonlinear
relationship between drug efficacy and cost-effectiveness, with drugs of low
efficacy producing high and variable cost-effectiveness ratios, particularly when
other programme costs related to distance travelled were high. The results
suggest that given the current price range of praziquantel, a drug with less than
a 50% chance of killing the worms is not to be recommended. This has important
practical implications for the widespread use of praziquantel, since most
international agencies procure praziquantel purely on the basis of price. There
is clearly a need for studies which evaluate the efficacy of new brands of
praziquantel, and more credence should be given to the use of high efficacy
brands, not only in terms of maximizing the cost-effectiveness of the
intervention programme, but also in delaying the onset of drug resistance.
PMID- 9657505
TI - Verbal autopsies for adult deaths: their development and validation in a
multicentre study.
AB - BACKGROUND: Verbal autopsy (VA) has been widely used to ascertain causes of child
deaths, but little is known about the usefulness of VA for adult deaths. This
paper describes the process used to develop a VA tool for adult deaths and the
results of a multicentre validation of this tool. METHODS: A mortality
classification was developed by including causes of death that might be arrived
at by VAs and causes that are responsive to public health interventions. An
algorithm was designed for each cause in the classification, based on classifying
symptoms into essential, supportive and differential. A structured questionnaire
designed to elicit information on these symptoms was developed in English
translated into the local languages. The tool was validated on deaths occurring
at hospitals in Tanzania (315 deaths), Ethiopia (249) and Ghana (232). Hospital
records of all adult deaths occurring at the study hospitals from June 1993 to
April 1995 were collected prospectively. Non-medical interviewers with at least
12 years of formal education conducted VA interviews. Causes of death were
diagnosed by a panel of physicians and by a computerized algorithm. The validity
of the VA was assessed by comparing the VA diagnoses with hospital diagnoses.
RESULTS: Specificity of VAs by physicians fell below 95% only for acute febrile
illness (AFI) and TB/AIDS. Sensitivity and positive predictive value (PPV),
however, varied widely both across the sites and between causes. Sensitivity was
> 75% for tetanus, rabies, direct maternal causes, injuries and TB/AIDS and
ranged between 60% and 74% for diarrhoea, acute abdominal conditions and AFI. The
PPV was > 75% for tetanus, rabies, hepatitis and injuries and ranged between 60
and 74% for meningitis, AFI, TB/AIDS and direct maternal causes. When the
communicable diseases were combined in a single group, the sensitivity was 82%,
specificity 78% and PPV 85%. For the group of noncommunicable diseases the
corresponding sensitivity, specificity and PPV were 71%, 87% and 67%,
respectively. Use of an algorithm resulted in lower sensitivity, specificity and
PPV than the VAs by physician. CONCLUSION: VAs by a panel of physicians performed
better than an opinion-based algorithm. The validity of VA diagnosis was highest
for AFI, direct maternal causes, TB/AIDS, tetanus, rabies and injuries.
PMID- 9657506
TI - Maternal anthropometry-based screening and pregnancy outcome: a decision
analysis.
AB - OBJECTIVE: To assess the impact of screening and intervention based on maternal
height, prepregnancy weight and weight during weeks 16-19 or 24-27 in reducing
adverse pregnancy outcomes (IUGR, preterm birth and assisted delivery) in
developing country settings. METHODS: Decision analysis based on a recent
multicentre WHO collaborative study of maternal anthropometry and pregnancy
outcomes and meta-analyses of controlled clinical trials of balanced
energy/protein supplementation (for IUGR and preterm birth) and support from
caregivers during labour (for assisted delivery). Subjects for the analysis
comprised pregnant women from Cali, Colombia (1989, n = 4598); urban and rural
Pune, India (1990, n = 4307); and urban and rural Myanmar (1981-82, n = 3542)
followed until delivery. RESULTS: Seven to 45% of pregnant women had positive
screens, with preventive fractions (PFs) ranging from 0.034 to 0.109 for IUGR,
0.027-0.082 for preterm birth and 0.011-0.105 for assisted delivery. Screening
prevention ratios (SPRs = ratios of the number of women treated to the number of
cases of adverse outcome prevented) are high in all three study settings for
preterm birth and assisted delivery (range 22.8-115.7) and low in settings with a
high prevalence of the adverse outcome and high specificity of the anthropometric
measure (India for IUGR, range 7.0-8.0). Sensitivity analyses demonstrate a
marked linear fall in PF and an exponential rise in the SPR as the relative risk
associated with intervention increases (i.e. as the protective benefit of
intervention decreases) from 0.60 to 0.95. CONCLUSIONS: A maternal anthropometry
based 'risk approach' is unlikely to result in a major reduction in adverse
pregnancy outcomes in developing country settings. For risk-free and inexpensive
interventions (e.g. caregiver support during labour), a better strategy would be
to forego screening and instead treat all pregnant women.
PMID- 9657507
TI - Financing changes of schistosomiasis control programmes in China 1980-1995: a
case study in Songzi county.
AB - To assess the financing changes of schistosomiasis control programmes in China
and estimate the impact of these changes on patients' treatment-seeking behaviour
and control of schistosomiasis, a survey was conducted in five schistosomiasis
endemic areas of the lake regions, Hubei province, in 1996. This paper reports
financing changes and their impact on the incidence and prevalence of
schistosomiasis from one of the five areas as a case study. By examining the
surveillance and financial data from 1980 to 1995, and through focus group
discussions we found that the schistosomiasis control programmes in People's
Republic of China have gone through dramatic financing changes from 1980 to 1995,
when the transitions of China's social, economic, and political systems happened.
The proportions of funding to schistosomiasis control programmes from high level
governmental agencies, county budgets, and services revenue changed from 60%,
23%, and 17%, respectively, in 1980-1987 to 0.7%, 22.3%, and 72% in 1995. The
percentages of expenditure of schistosomiasis control activities, salaries and
bonuses, and other activities unrelated to schistosomiasis control, were 53.5%,
14.4, and 17.2% in 1980. These percentages changed to 7.7%, 33.3%, and 53.3%,
respectively, in 1995. The preponderant role of the state in organizing,
financing, and delivery of the services was replaced with the new system which is
more influenced by the market economy. The incidence and the prevalence of
schistosomiasis in the study area have increased year by year from 1980 to 1990,
although there has been a tendency to decrease after 1991 but not to the low
pre1980 levels. The collapse of the community-based medical system in rural areas
and the dramatic financing changes of schistosomiasis control programmes have
created major difficulties for schistosomiasis control in China.
PMID- 9657508
TI - Albendazole plus praziquantel versus albendazole alone as a pre-operative
treatment in intra-abdominal hydatisosis caused by Echinococcus granulosus.
AB - OBJECTIVE: To compare the effects of a combined medication of albendazole (10
mg/kg/day) plus praziquantel (25 mg/kg/day) to those of albendazole alone at
different doses (10 and 20 mg/kg/day). METHOD: The protoscoleces' viability was
studied in a consecutive series of patients affected by intra-abdominal
hydatidosis caused by Echinococcus granulosus. In all cases the drugs were given
during the month prior to surgery. RESULTS: A significant increase of patients
with nonviable protoscoleces was observed in the group treated with the
scolicides combination compared to those treated with albendazole alone, both at
a dose of 10 mg/kg/day (P = 0.004) and at a dose of 20 mg/kg/day (P = 0.03).
Albendazole sulphoxide levels in serum and in cyst fluid were higher in patients
given the combined therapy than in those who received only albendazole (10
mg/kg/day: P = 0.016; 20 mg/kg/day: P = 0.034). Levels in the cysts were not
significantly different probably due to the sample size; nevertheless a lineal
relation between the values obtained in serum and inside the cysts could be
discerned in the patients treated with the combined medication. CONCLUSION:
Albendazole plus praziquantel is more effective than monotherapy with albendazole
in the preoperative treatment of intra-abdominal hydatidosis.
PMID- 9657509
TI - Filarial elephantiasis among Haitian women: social context and behavioural
factors in treatment.
AB - Few studies have addressed the social and behavioural aspects of lymphatic
filariasis. The research reported here investigated the ethnographic context of
filarial elephantiasis among women in Leogane, Haiti, and focused on explanatory
models of the illness, the impact of the disease on women's lives, and the
difficulties patients experienced in following a therapeutic regimen provided at
a local hospital. Qualitative data were collected through focus group and
individual interviews and direct observation of patients enrolled in the
treatment programme. Results indicate that traditional understanding and
treatment for the disease are prevalent in the community, although biomedical
explanations are gaining credence as a consequence of long-term filariasis
control activities in this area. Women's lives are substantially burdened both
socially and economically by the physical impairment of elephantiasis, most
notably in the loss of income due to restrictions on mobility. The degree of
social discrimination encountered varies by the timing of onset of symptoms in
the life course. Difficulties encountered with the physical therapy regimen
included maintenance of the compressive bandage and availability of suitable foot
wear. Similarities between these findings and those reported for other parts of
the world are noted. Recommendations from the study cite the need for community
education and peer support activities to provide a knowledge base and support
structure for current and future intervention programmes.
PMID- 9657510
TI - Key indicators for the monitoring and evaluation of control programmes of human
African trypanosomiasis due to Trypanosoma brucei gambiense.
AB - Very little research has been devoted to the design of epidemiological tools for
the monitoring and evaluation of National Human African Trypanosomiasis (HAT)
Control Programmes and daily management decisions are made in the absence of
accurate knowledge of the situation. This paper identifies key indicators
necessary to make decisions in the field and constantly adjust control activities
to changing situations. Examples are derived from the Medecins Sans Frontieres
(MSF) HAT Control Programme in Adjumani, Uganda. Based on the principles of
quality assurance, the focus is placed on process indicators. A conceptual
framework derived from a system view/planning cycle perspective is also described
for the construction of indicators. Finally, some specific challenging aspects of
the epidemiology of HAT are presented and the limitations of the interpretation
of the indicators discussed.
PMID- 9657511
TI - Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian
subjects and in patients with falciparum malaria.
AB - OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with
and without malaria. METHOD: Quinine-dihydrochloride was administered
intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple
doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma
quinine concentrations were measured by high-performance liquid chromatography
RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination
halftime is shorter in the accumulation phase than in the elimination phase; in
malaria patients the maximal quinine concentration was reached in half the time
calculated on the basis of the elimination phase after the last quinine infusion.
Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels
quickly. In malaria patients the highest plasma concentrations during or at the
end of the infusions were positively correlated with body weight. There was no
correlation between body weight and the volume of distribution of quinine as
calculated during the elimination phase. Hearing loss was audiometrically
documented in 9 healthy subjects at a mean maximal plasma quinine concentration
of only 2 mg/l. All malaria patients suffered serious cochlear hearing
impairment. The ototoxic effects in both healthy subjects and patients appeared
to be reversible. No electrographic changes were noted in the healthy subjects,
whereas a clinically insignificant mean lengthening of the corrected QT interval
was seen in the malaria patients. CONCLUSION: Intravenous quinine
pharmacokinetics in healthy Caucasians were similar to those reported for
Nigerian or Thai subjects. At effective doses quinine causes considerable but
reversible cochlear hearing losses in both healthy persons and in patients. Our
findings do support the need for a loading dose. The fact that in malaria
patients there was no correlation between body weight and quinine VD as
calculated during the elimination phase renders questionable the usefulness of
dosing quinine according to body weight.
PMID- 9657512
TI - Distinction of recrudescences from new infections by PCR-RFLP analysis in a
comparative trial of CGP 56 697 and chloroquine in Tanzanian children.
AB - OBJECTIVE: To test the efficacy of a new compound drug (CGP 56697) against acute,
uncomplicated falciparum malaria. METHOD: Reappearing parasites were analysed by
PCR-RFLP within a randomized controlled trial. 130 patients received chloroquine
and 130 patients were treated with CGP 56697. Samples from 96 patients with
parasitological failure were tested by PCR-RFLP for MSP2 of Plasmodium
falciparum. Seven days after treatment 32 patients of the chloroquine control
group with reappearing parasites were tested by PCR and one infection was
unequivocally determined as a new infection. After 7 days, in the CGP 56697
group, 6 samples were tested in which one new infection was identified. Similar
observations were made one and three weeks later in both groups. RESULTS:
Although a high multiplicity of infections on admission was observed, there was
no significant correlation between multiplicity and either recrudescence or new
infection. Patients in both treatment groups with subsequent recrudescent
parasites had higher initial mean parasite densities than patients who cleared.
Those of the patients with recrudescent parasites who were treated with CGP 56697
had higher initial parasite densities than those treated with chloroquine. The
rate of re-infection increased with time as expected in holoendemic areas and
appeared to be higher in chloroquine patients. Generally, CGP 56697 showed a
superior clearance rate, successfully cleared higher parasite densities and
suppressed new infections over a longer period of time. CONCLUSION: The PCR
analysis confirmed that reinfections beyond day 7 are significant in areas highly
endemic for malaria and showed the necessity of excluding these when estimating
14 day clearance rates. Provided new infections are excluded, the 28-day
clearance rate can also be used to determine the efficacy of antimalarial drugs
in highly endemic areas, and adds to our knowledge of drug resistance and
dynamics of infections in people living in such areas.
PMID- 9657513
TI - Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with
chloroquine to treat acute falciparum malaria in Tanzanian children aged 1-5
years.
AB - A randomized, open trial involving 260 Tanzanian children, aged 1-5 years, with
acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the
combination antimalarial CGP 56697 (artemether and benflumetol), and to compare
it with chloroquine, the standard drug used for malaria treatment in the
Kilombero area. Children who had received rescue medication within the first 48 h
or had a negative slide at the same time were excluded. Seven-day parasitological
cure rates were 94% (95% CI 88-97.5) for CGP 56697 and 35.4% (95% CI 25.9-45.8)
for chloroquine. Using the same definition, the 14-day parasitological cure rates
were 86.4% (95% CI 78.5-92.2) for CGP 56697 and 10.3% (95% CI 5.1-18.1) for
chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by
chloroquine. There were no major adverse events with either drug. CGP 56697 is
highly efficacious against P. falciparum in this area of Tanzania. The study
contributes to the discussion on treatment strategies, particularly whether
chloroquine may still fulfil its role as first-line drug in an area of high
malaria transmission and very high levels of chloroquine resistance.
PMID- 9657514
TI - Human occult loiasis: field evaluation of a nested polymerase chain reaction
assay for the detection of occult infection.
AB - A nested polymerase chain reaction (nested PCR) assay, targeted on the repeat 3
region (15r3) of the gene coding for a Loa loa 15 kD polyprotein, was developed
to detect L. loa infection. The assay has a sensitivity of 95% and is 100%
specific with regard to sympatric filarial parasites: Mansonella perstans,
Onchocerca volvulus and Wuchereria bancrofti. In this field study in a mixed
filarial (L. loa and M. perstans) endemic region of Gabon, 157 L. loa
amicrofilaraemic blood samples (AMF; diagnosed by leucoconcentration followed by
standard microscopic examination) from the residents from four villages were
screened by the 15r3-nested PCR assay. The assay detected 106 occult infected
subjects among the 157 AMF individuals (68%), including 59 of 87 adults (68%) and
47 of 70 children (67%). In each village the prevalence of occult infection was,
respectively, 38%, 52%, 79% and 80% for Moyabi, Djoutou, N'djokaye and Okoumbi.
The annual transmission potential (ATP) of loiasis has been estimated to be 250
infective larvae (L 3) per man per year for Moyabi and Djoutou, 1800 for
N'djokaye and 433000 L3/man/year for Okoumbi. This implies a correlation between
occult infection of loiasis and the intensity of transmission. By contrast, the
prevalence of L. loa microfilariae was 21% for Okoumbi, 22%, for N'djokaye and
19% for Djoutou and Moyabi. These results show that the prevalence of loiasis in
this region of Gabon is higher than previously described by standard microscopic
examination and that the application of this assay will be significant in the
development of control strategies for loiasis.
PMID- 9657515
TI - Towards new partnerships for health development in developing countries: the
contractual approach as a policy tool.
AB - What roles for government but also for society's groups in the advancement of
public health in developing countries? This paper focuses on the need to adopt
the contractual approach as a powerful policy tool and sketches the contours of a
policy framework for good contracting. A short historical review of health system
changes leads up to a discussion of the current emergence of a multitude of
actors, the forging of alliances between the various partners, examples on how
significant health policy benefits might be secured through contracting, and the
implications of building alliances, such as defining and assigning accountability
to the contracting partners.
PMID- 9657516
TI - A bill of responsibilities for whistleblowers in science.
PMID- 9657517
TI - A new look at thin filament regulation in vertebrate skeletal muscle.
AB - It is 30 years since Ebashi and colleagues showed that Ca2+ ions directly affect
regulation of the myosin-actin interaction in muscle through the action of
tropomyosin and troponin on muscle thin filaments. It is more than 20 years since
the idea was put forward that tropomyosin might act, at least in part, by
changing its position on actin, thus uncovering or modifying the myosin binding
site on actin when troponin molecules take up Ca2+. Since that time, a great deal
of evidence for and against this steric blocking mechanism has been published: a
structure for actin filaments at close to atomic resolution has been proposed,
and the whole regulation story has become both more complicated and more subtle.
Here we review structural and biochemical aspects of regulation in vertebrate
skeletal muscle. We show that some basic ideas of the steric blocking mechanism
remain valid. We also show that additional factors, such as troponin movements
and structural changes within the actin monomers themselves, may be crucial. A
number of the resulting regulation scenarios need to be distinguished.
PMID- 9657518
TI - Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS
I and NOS III).
AB - Nitric oxide synthase (NOS) exists in three established isoforms. NOS I (NOS1,
ncNOS) was originally discovered in neurons. This enzyme and splice variants
thereof have since been found in many other cells and tissues. NOS II (NOS2,
iNOS) was first identified in murine macrophages, but can also be induced in many
other cell types. NOS III (NOS3, ecNOS) is expressed mainly in endothelial cells.
Whereas NOS II is a transcriptionally regulated enzyme, NOS I and NOS III are
considered constitutively expressed proteins. However, evidence generated in
recent years indicates that these two isoforms are also subject to expressional
regulation. In view of the important biological functions of these isoforms,
changes in their expression may have physiological and pathophysiological
consequences. This review recapitulates compounds and conditions that modulate
the expression of NOS I and NOS III, summarizes transcriptional and
posttranscriptional effects that underlie these changes, and-where known
describes the molecular mechanisms leading to changes in transcription, RNA
stability, or translation of these enzymes.
PMID- 9657519
TI - Proteins that specifically recognize cisplatin-damaged DNA: a clue to anticancer
activity of cisplatin.
AB - Cisplatin, but not its trans geometric isomer, is a potent anticancer drug whose
biological activity is a consequence of the formation of covalent adducts between
the platinum compound and certain bases in DNA. Two classes of proteins have
recently been identified that bind preferentially to damaged sites: proteins that
specifically recognize those sites as a first step in their repair, and those
that bind to such sites by virtue of structural similarity between the modified
DNA and their own natural binding sites. Both classes of proteins may be
involved, perhaps in opposing ways, in the cytotoxic effect of the drug.
PMID- 9657520
TI - Antisense telomerase treatment: induction of two distinct pathways, apoptosis and
differentiation.
AB - Telomerase, the enzyme that elongates telomeric DNA (TTAGGG)n, may be involved in
cellular immortality and oncogenesis. To investigate the effect of inhibition of
telomerase on tumor cells, we transfected the antisense vector against the human
telomerase RNA into human malignant glioma cells exhibiting telomerase activity.
After 30 doublings, some subpopulations of transfectants expressed a high level
of interleukin-1beta-converting enzyme (ICE) protein and underwent apoptosis. In
contrast, other subpopulations also showed enhanced ICE protein but escaped from
apoptotic crisis and continued to grow, although their DNA synthesis, invasive
ability, and tumorigenicity in nude mice were significantly reduced. Surviving
cells demonstrated increased expression of glial fibrillary acidic protein and
decreased motility, consistent with a more differentiated state. These cells also
contained enhanced expression of the cyclin-dependent kinase inhibitors (CDKIs)
p21 and p27. Treatment of surviving nonapoptotic cells with antisense
oligonucleotides against p27, but not p21, induced apoptotic cell death,
suggesting that p27 may have protected differentiating glioma cells from
apoptosis. These data show that treatment with antisense telomerase inhibits
telomerase activity and subsequently induces either apoptosis or differentiation.
Regulation of these two distinct pathways may be dependent on the expression of
ICE or CDKIs.
PMID- 9657522
TI - Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation
mechanism.
AB - Human low density lipoprotein (LDL) is prepared in the presence of antioxidants
and is oxidized to different levels (measured by thiobarbituric acid reactive
substance) with copper ion. The effects of unoxidized LDL and oxidized LDL (ox
LDL) on stress fiber formation, cell membrane ruffling, and pinocytosis (measured
by [14C]sucrose uptake) in cultured human umbilical cord vein endothelial cells
(EC) are compared. We show that at a concentration range of 100 to 200 microg
cholesterol/ml, both unoxidized LDL and ox-LDL promote EC elongation and stress
fiber formation, but the effect by the latter is more prominent when compared at
the same dose range. In addition, ox-LDL also induces EC membrane ruffling and
promotes pinocytosis. These effects are positively correlated with the extent of
LDL oxidation and depend on the dose of ox-LDL. Ox-LDL-promoted membrane ruffling
and pinocytosis are effectively blocked by brief preexposure of the cells to
antioxidants. In contrast, stress fiber formation is not affected by antioxidant
pretreatment. Although unoxidized LDL also promotes [14C]sucrose uptake, it is
less potent than ox-LDL and significantly higher concentrations are required to
produce a detectable effect. Unlike ox-LDL, unoxidized LDL-enhanced pinocytosis
is not accompanied by the appearance of membrane ruffling; therefore, they may
act via different mechanisms. Elevated pinocytosis may increase transcytotic
activity of the endothelium, leading to an increased influx of plasma components
such as LDL into the subendothelial space.
PMID- 9657521
TI - The unimportance of being (protein kinase C) epsilon.
AB - The purpose of our study was to determine the mechanism through which phorbol
esters and smooth muscle myosin phosphatase inhibitors can induce contraction of
smooth muscle in the absence of Ca2+. Protein kinase C-epsilon (PKC-epsilon) was
previously implicated in this process based largely on its supposed absence in
the ferret portal vein, and a correlation was drawn between the presence of this
isoform and the ability of smooth muscle to contract independently of Ca2+ and
phosphorylation of the 20 kDa regulatory light chains of myosin (MLC20). We
demonstrate here, with two antibodies, one to the NH2 terminus and the other to
the COOH terminus of PKC-epsilon, that epsilon is present in both ferret portal
vein and rabbit portal vein smooth muscle, neither of which exhibits phorbol
ester-induced contraction in the absence of Ca2+. However, in the presence of
clamped submaximal Ca2+, phorbol es ter increased MLC20 phosphorylation from
17.7+/-1.7% to 46.4+/-3.6% in ferret portal vein smooth muscle and evoked an
increase in force. Prolonged (48 h) incubation of ferret portal vein with phorbol
esters completely down-regulated PKC-epsilon, as shown by Western blots, and
abolished the phorbol ester-evoked contraction at submaximal Ca2+, but not Ca2+
independent, contractions induced by the phosphatase inhibitor microcystin.
Contractions induced by microcystin in Ca2+-free solution were associated with
increased phosphorylation of myosin light chain kinase (MLCK). Activation of MLCK
by autophosphorylation in the absence of Ca2+ occurs in vitro (1). We conclude
that PKC-epsilon is neither necessary nor sufficient for Ca2+-independent
regulation of myosin II in smooth muscle, but contractions induced by agents that
inhibit smooth muscle myosin phosphatase in the absence of Ca2+ may be mediated
by MLCK autophosphorylated or activated by another Ca2+-independent kinase.
PMID- 9657523
TI - Localization, quantification, and activation of platelet-activating factor
receptor in human endometrium during the menstrual cycle: PAF stimulates NO,
VEGF, and FAKpp125.
AB - Implantation is characterized by an inflammatory-like response with expansion of
extracellular fluid volume, increased vascular permeability, and vasodilatation.
These effects are believed to be mediated at the paracrine level by prostaglandin
E2 and platelet-activating factor (PAF), but the cellular mechanism (or
mechanisms) remains largely unknown. We demonstrate that PAF receptor (PAF-R)
immunoreactivity and mRNA are detected in proliferative and secretory endometrial
glands, however, the responsiveness of endometrium to physiological
concentrations of PAF is confined predominantly to the secretory endometrium.
Semiquantitative reverse transcription-polymerase chain reaction revealed that
PAF-R transcript levels were highest in the mid-late proliferative and late
secretory phases of the cycle. Interaction of PAF with its receptor resulted in
the rapid release of nitric oxide (NO), increased expression of vascular
endothelial growth factor (VEGF), and activation of FAKpp125, a focal adhesion
kinase, demonstrating that the PAF-R is functionally active. Inhibition of NO
synthesis by NG-monomethyl-L-arginine produced dose-dependent attenuation of PAF
evoked NO release, indicating NOS activation; the dependency of PAF-evoked NO
release on PKC and extracellular Ca2+ was confirmed by PKC inhibitor Ro 31-8220
and by the removal of extracellular Ca2+. PAF up-regulated VEGF gene expression
in a concentration- and time-dependent fashion in human endometrial epithelial
cell lysates. Transcription of VEGF was rapidly followed by secretion of the
protein. These data support our premise that this autocoid acts as an angiogenic
mediator in the regeneration of the endometrium after menses and as a vasodilator
to promote blastocyst attachment during the implantation process.
PMID- 9657524
TI - TR1, a new member of the tumor necrosis factor receptor superfamily, induces
fibroblast proliferation and inhibits osteoclastogenesis and bone resorption.
AB - A newly identified member of the tumor necrosis factor receptor (TNFR)
superfamily shows activities associated with osteoclastogenesis inhibition and
fibroblast proliferation. This new member, called TR1, was identified from a
search of an expressed sequence tag database, and encodes 401 amino acids with a
21-residue signal sequence. Unlike other members of TNFR, TR1 does not contain a
transmembrane domain and is secreted as a 62 kDa glycoprotein. TR1 gene maps to
chromosome 8q23-24.1 and its mRNA is abundantly expressed on primary osteoblasts,
osteogenic sarcoma cell lines, and primary fibroblasts. The receptors for TR1
were detected on a monocytic cell line (THP-1) and in human fibroblasts.
Scatchard analyses indicated two classes of high and medium-high affinity
receptors with a kD of approximately 45 and 320 pM, respectively. Recombinant TR1
induced proliferation of human foreskin fibroblasts and potentiated TNF-induced
proliferation in these cells. In a coculture system of osteoblasts and bone
marrow cells, recombinant TR1 completely inhibited the differentiation of
osteoclast-like multinucleated cell formation in the presence of several bone
resorbing factors. TR1 also strongly inhibited bone-resorbing function on dentine
slices by mature osteoclasts and decreased 45Ca release in fetal long-bone organ
cultures. Anti-TR1 monoclonal antibody promoted the formation of osteoclasts in
mouse marrow culture assays. These results indicate that TR1 has broad biological
activities in fibroblast growth and in osteoclast differentiation and its
functions.
PMID- 9657525
TI - Protein kinase A type I antagonist restores immune responses of T cells from HIV
infected patients.
AB - Cyclic AMP-dependent protein kinase A (PKA) type I has been established as an
acute inhibitor of T cell activation. For this reason, we investigated the
possible role of PKA type I in HIV-induced T cell dysfunction. T cells from HIV
infected patients have increased levels of cAMP and are more sensitive to
inhibition by cAMP analog than are normal T cells. A PKA type I-selective
antagonist increases the impaired proliferation of T cells from HIV-infected
patients to normal or subnormal levels (up to 2.8-fold). Follow-up of patients
after initiation of highly active antiretroviral treatment revealed that a
majority of patients have a persistent T cell dysfunction that is normalized by
incubation of T cells with Rp-8-Br-cAMPS. These observations imply that increased
activation of PKA type I may contribute to the progressive T cell dysfunction in
HIV infection and that PKA type I may be a potential target for immunomodulating
therapy.
PMID- 9657526
TI - Redox priming of the insulin receptor beta-chain associated with altered tyrosine
kinase activity and insulin responsiveness in the absence of tyrosine
autophosphorylation.
AB - Induction of tyrosine kinase activity of the insulin receptor (IR) beta-chain is
believed to require its autophosphorylation at Tyr1162, Tyr1163, and Tyr1158.
However, the mechanism of the initial phosphorylation is poorly understood. We
show that treatment of IR-transfected Chinese hamster ovary cells with
antioxidants inhibits insulin responsiveness. Conversely, partial inhibition of
glutathione biosynthesis by buthionine sulfoximine (BSO) and glutathione
reductase by 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), i.e., procedures that
intracellularly induce mildly oxidative conditions, caused a decrease in IR beta
chain sulfhydryl groups and enhanced synergistically the induction of IR tyrosine
phosphorylation by insulin. The IR beta-chain from cells treated with BSO/BCNU in
the absence of insulin was not detectably tyrosine phosphorylated, but
nevertheless was functionally altered, as demonstrated in vitro by a moderate
kinase activity at lowATP concentrations (5 nM) and a strong kinase activity at
25 microM ATP. This activity was found to be specific for tyrosine (not for
serine or threonine), and tryptic peptide maps indicated that it is more
selective than that induced by insulin. Moreover, the kinase activity from
BSO/BCNU-treated cells showed a spontaneous decay that was not prevented by the
phosphatase inhibitor vanadate. Together, these results suggest that optimal
insulin responsiveness may require a process of 'redox priming' of the IR beta
chain that involves structural and functional changes in the absence of
detectable tyrosine phosphorylation of the beta-chain.
PMID- 9657527
TI - Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF
kappaB activation in response to tumor necrosis factor alpha.
AB - Skeletal muscle atrophy and weakness are thought to be stimulated by tumor
necrosis factor alpha (TNF-alpha) in a variety of chronic diseases. However,
little is known about the direct effects of TNF-alpha on differentiated skeletal
muscle cells or the signaling mechanisms involved. We have tested the effects of
TNF-alpha on the mouse-derived C2C12 muscle cell line and on primary cultures
from rat skeletal muscle. TNF-alpha treatment of differentiated myotubes
stimulated time- and concentration-dependent reductions in total protein content
and loss of adult myosin heavy chain (MHCf) content; these changes were evident
at low TNF-alpha concentrations (1-3 ng/ml) that did not alter muscle DNA content
and were not associated with a decrease in MHCf synthesis. TNF-alpha activated
binding of nuclear factor kappaB (NF-kappaB) to its targeted DNA sequence and
stimulated degradation of I-kappaBalpha, an NF-kappaB inhibitory protein. TNF
alpha stimulated total ubiquitin conjugation whereas a 26S proteasome inhibitor
(MG132 10-40 microM) blocked TNF-alpha activation of NF-kappaB. Catalase 1 kU/ml
inhibited NF-kappaB activation by TNF-alpha; exogenous hydrogen peroxide 200
microM activated NF-kappaB and stimulated I-kappaBalpha degradation. These data
demonstrate that TNF-alpha directly induces skeletal muscle protein loss, that NF
kappaB is rapidly activated by TNF-alpha in differentiated skeletal muscle cells,
and that TNF-alpha/NF-kappaB signaling in skeletal muscle is regulated by
endogenous reactive oxygen species.
PMID- 9657528
TI - Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients
and retrovirus-infected macaques.
AB - This study investigated the sources of quinolinic acid, a neurotoxic tryptophan
kynurenine pathway metabolite, in the brain and blood of HIV-infected patients
and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV
infected patients were elevated by > 300-fold to concentrations that exceeded
cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations
between elevated serum quinolinic acid levels with those in CSF and brain
parenchyma. Because nonretrovirus-induced encephalitis confounds the
interpretation of human postmortem data, rhesus macaques infected with retrovirus
were used to examine the mechanisms of increased quinolinic acid accumulations
and determine the relationships of quinolinic acid to encephalitits and systemic
responses. The largest kynurenine pathway responses in brain were associated with
encephalitis and were independent of systemic responses. CSF quinolinic acid
levels were also elevated in all infected macaques, but particularly those with
retrovirus-induced encephalitis. In contrast to the brain changes, there was no
difference in any systemic measure between macaques with encephalitis vs. those
without. Direct measures of the amount of quinolinic acid in brain derived from
blood in a macaque with encephalitis showed that almost all quinolinic acid
(>98%) was synthesized locally within the brain. These results demonstrate a role
for induction of indoleamine-2,3dioxygenase in accelerating the local formation
of quinolinic acid within the brain tissue, particularly in areas of
encephalitis, rather than entry of quinolinic acid into the brain from the
meninges or blood. Strategies to reduce QUIN production, targeted at
intracerebral sites, are potential approaches to therapy.
PMID- 9657529
TI - Apolipoprotein A-I production by chicken granulosa cells.
AB - In avian species such as the chicken, development of the oocyte is associated
with massive deposition of yolk in this cell. Oocytes grow within the follicle, a
compartment consisting of a very specialized set of cells and acellular
structures. The oocyte is surrounded by the perivitelline layer and granulosa
cells, which are separated from the thecae by a pronounced basement membrane. In
addition to the production of yolk precursors in the liver, we have long implied
that cells within the follicle make a direct contribution to the growth of the
oocyte. Here we show that chicken granulosa cells express and actively secrete
apolipoprotein A-I (apoA-I) as a part of particles with very high density. The
granulosa cell-derived, apoA-I-containing material is different from the small
portion of yolk high density lipoprotein that arises via transfer from the
peripheral circulation. We propose that the ApoA-I-containing particles secreted
by granulosa cells 1) support the growth of the rapidly growing germ cell,
possibly by direct lipid transfer to the plasma membrane of the oocyte, and/or 2)
deliver cholesteryl esters to the steroid-producing cells of the theca layer.
These findings are discussed with respect to the proposed functions of apoE (an
apolipoprotein not found in chicken) within the mammalian follicle.
PMID- 9657530
TI - Neuroprotection by bromocriptine against 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine-induced neurotoxicity in mice.
AB - Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30
mg/kg i.p. twice, 16 h apart). This resulted in changes in motor performance and
toxic insult of nigral neurons as evidenced by dopamine depletion in nucleus
caudatus putamen. In vitro and in vivo treatment of MPTP caused the generation of
hydroxyl radicals (.OH) as measured by a sensitive salicylate hydroxylation
procedure. A dopamine agonist, bromocriptine (10 microM and 10 mg/kg i.p.),
blocked .OH formation caused by MPTP in vitro (20 microM) and in vivo (30 mg/kg
i.p.). An MPTP-induced increase in the activity of catalase and superoxide
dismutase in substantia nigra on the seventh day was reduced by bromocriptine
pretreatment. Bromocriptine blocked MPTP-induced behavioral dysfunction as well
as glutathione and dopamine depletion, indicating its potent neuroprotective
action. This study suggests that bromocriptine stimulates antioxidant mechanisms
in the brain and acts as a free radical scavenger in addition to its action at
dopamine receptors, thus indicating its strength as a valuable neuroprotectant.
PMID- 9657532
TI - The renin-angiotensin system: the centenary jubilee.
PMID- 9657531
TI - The renin-angiotensin system--a century of progress.
PMID- 9657533
TI - Normotensive offspring with non-dipper hypertensive parents have abnormal sleep
pattern.
AB - The objective of this study was to determine whether abnormal microstructure of
sleep in non-dipper hypertensive patients was present in their offspring.
Subjects included 11 normotensive offspring of non-dipper hypertensive parents
(FH + ND), 6 of dipper hypertensive parents (FH + D) and 5 of normotensive
parents (Controls). We measured blood pressure beat-to-beat by Finapres and all
stages of sleep by polysomnographically recording simultaneously during
spontaneous nocturnal sleep. We analysed blood pressure pattern for 4-min long
random periods while the subjects were awake and during all stages of sleep;
sleep efficiency (SE), sleep latency (SL), delta-sleep latency (delta-SL), REM
sleep latency (REM-SL), Stage 1, Stage 2, Stage 3, Stage 4 and REM duration and
percentage values, and microstructural aspects of sleep (arousal and microarousal
temporization and features). FH + D and controls showed a fall in blood pressure
greater than 10% in all stages of NREM sleep and in the FH + ND blood pressure
fall in less than 10% of waking values in all NREM stages. REM sleep and heart
rate were similar in the three groups during all stages of sleep. FH + ND showed
the same number of arousals but more microarousals than FH + D and controls (p <
0.0001). Microarousals induced several stage shifts through lighter sleep. For
this reason, FH + ND spent more time in stage 2 than FH + D and controls. In
conclusion, offspring of non-dipper hypertension parents showed a greater number
of microarousals than the other two groups.
PMID- 9657534
TI - Prognosis during five years of follow-up among patients admitted to the emergency
department with acute chest pain in relation to a history of hypertension.
AB - AIM: To describe the mortality, mode and place of death and risk indicators of
death during 5 years of follow-up among patients admitted to the emergency
department (ED) with acute chest pain or other symptoms raising a suspicion of
acute myocardial infarction (AMI) in relation to a history of hypertension.
METHODS: All the patients admitted to the ED at Sahlgrenska University Hospital
during a period of 21 months with acute chest pain or other symptoms raising a
suspicion of AMI were followed up prospectively for 5 years. RESULTS: Of 5,355
patients fulfilling the inclusion criteria, 22% had a history of hypertension.
Hypertensive patients differed from non-hypertensive patients in that there were
more females, they were older and had a higher prevalence of previous
cardiovascular disease. Patients with a history of hypertension had a 5-year
mortality rate of 37.4% as compared with 22.2% among non-hypertensive patients (p
< 0.001). The difference in mortality appeared to be more marked among patients
without a history of cardiovascular disease. A history of hypertension was an
independent predictor of death. Risk indicators of death appeared to be
relatively similar among patients with and without a history of hypertension. Of
the patients who died, those with a history of hypertension were more frequently
judged to have suffered a cardiac death and died more frequently in association
with an AMI. CONCLUSION: Among patients admitted to the ED with acute chest pain
and with a history of hypertension, 37% died during the following 5 years. A
history of hypertension was an independent predictor of death.
PMID- 9657535
TI - Insulin-like growth factor binding protein-1 as a marker of the metabolic
syndrome--a study in borderline hypertension.
AB - AIM: To evaluate insulin-like growth factor I (IGF-I) and insulin-like growth
factor binding protein-1 (IGFBP-1) in borderline hypertension (BHT) in relation
to plasma lipoprotein and insulin levels, anthropometric variables and 24-h
ambulatory blood pressure (BP). Seventy-five BHT men diastolic BP (DBP) 85-94
mmHg) and 75 age-matched normotensive controls (NT, DBP < or = 80 mmHg) were
recruited from a population-based screening program. RESULTS: There was no
difference in IGF-I or IGFBP-1 between BHT and NT men. However, subjects with
insulin resistance (IR) had decreased levels of IGF-1 (145 +/- 36 vs 153 +/- 28
microg/L, p < 0.05) and IGFBP-1 (41 +/- 15 vs 52 +/- 20 microg/L, p < 0.01)
compared to those without IR. IGF-I correlated inversely to BP levels in the BHT
group (r = -0.24 to -0.28, p < 0.05). IGFBP-1 correlated inversely with BMI,
lipoprotein and insulin levels (r = -0.29 to -0.48, p < 0.01), independent of IR.
CONCLUSION: While there are no differences between BHT and NT men in IGF-I and
IGFBP-1, both are significantly decreased in IR subjects. IGFBP-1 exhibits a
close correlation to metabolic factors. Decreased IGFBP-1 could thus be suggested
as a variable marking the "metabolic syndrome" of hypertension.
PMID- 9657536
TI - Effects of isolated systolic hypertension and essential hypertension on large and
middle-sized artery compliance.
AB - BACKGROUND: Systolic hypertension of the elderly is characterized by a reduction
in arterial compliance. Whether and to what extent this involves arteries of
various structure and size is not well known. OBJECTIVE: To study carotid and
radial artery compliance in systolic hypertension of the elderly, compared to
essential hypertension and normotension. METHODS: We investigated 28 elderly
patients with systolic hypertension (age 68.6 +/- 1.4 years, mean +/- SE;
systolic blood pressure > 160 mmHg and diastolic blood pressure < 90 mmHg) plus
17 age-matched patients with essential hypertension and 15 age-matched healthy
normotensive subjects. Radial and carotid artery compliance were evaluated using
echotracking techniques. In both arteries compliance was assessed statistically
and dynamically, i.e. as compliance values throughout the diasto-systolic
pressure range. Measurements included intima-media wall thickness of the radial
artery. RESULTS: Compared to normotensive subjects, carotid artery compliance was
reduced in essential hypertension and more so in systolic hypertension. However,
although in both groups radial artery wall thickness was markedly greater than in
the normotensive group, radial artery compliance was markedly reduced in systolic
hypertension, but unchanged in essential hypertension. CONCLUSIONS: In systolic
hypertension of the elderly the reduction of arterial compliance is marked in
both muscular and large elastic arteries, while in elderly essential
hypertensives changes in arterial compliance are more heterogeneous, i.e. only
carotid artery compliance is reduced. The different effects of these two types of
hypertension on arterial mechanics are visible throughout the physiological range
of blood pressure and probably accounted for by different alterations in vessel
wall structure.
PMID- 9657537
TI - The diurnal variation in blood pressure should be calculated from individually
defined day and night times.
AB - The aim of this study was to compare the nocturnal fall in BP parameters
calculated from individually defined periods of day and night to values computed
from collectively fixed day/night definitions. Day and night periods were defined
according to 3 different methods: (i) the individually defined time of getting up
and going to bed obtained from participant diaries (MethodIND); (ii) the mean
time of rising and retiring in the group (MethodMEAN); and (iii) a daytime period
from 07.00-22.00 h as recommended by The Scientific Committee (Method722). The
ambulatory BP was recorded every 30 min over 24 h. One hundred and eighty-seven
persons aged 40-66 years participated. With MethodIND, the BP load, systolic,
diastolic and mean BPs were higher in the daytime and lower in the night-time
compared to the results using Method722 and MethodMEAN. The nocturnal BP fall
using MethodIND was larger than the fall calculated from every possible fixed
division in the period from 3 h before till 3 h after the group mean time of
getting up and going to bed (p < 0.001). The lowest frequency of non-dipping,
defined as a nightly fall in systolic and diastolic BP below 10%, was observed
using MethodIND (10%). Compared to MethodIND, 11% were misclassified as non
dippers by Method722 and 8% by MethodMEAN. We conclude that the diurnal blood
pressure variation based on individually defined periods of day and night is
larger than the variation based on any collectively fixed day/night definition.
It is recommended that assessment of the nocturnal change in BP be based on
individually defined periods of day and night.
PMID- 9657538
TI - Effects of amlodipine and lisinopril on left ventricular mass and diastolic
function in previously untreated patients with mild to moderate diastolic
hypertension.
AB - The aim of the study was to compare the effects of two long-acting
antihypertensive agents, the calcium-antagonist amlodipine and the ACE inhibitor
lisinopril, on left ventricular mass and diastolic filling in patients with mild
to moderate diastolic hypertension from primary care centres. It is a 1-year
prospective, double-blind, randomized, parallel group, comparative study.
Patients between 25 and 75 years of age with untreated hypertension with elevated
diastolic blood pressure (> or = 95 mmHg) on three occasions (twice on the first
visit and once only on the second and third visits) were recruited from a
population survey. After 4 weeks placebo run-in 71 patients were randomized to
dosages of amlodipine 5-10 mg or lisinopril 10-20 mg, which were titrated on the
basis of the effects on blood pressure. Fifty-nine patients completed the study
period. Primary endpoints were left ventricular mass index and early to atrial
peak filling velocity. Office and ambulatory blood pressure and other
echocardiographic measurements were considered secondary. Decrease in blood
pressure was equal for both treatment regimens. A statistically significant
decrease in left ventricular mass index in both treatment groups was observed:
11.0 g/m2 (95% CI: -6.0, -16.1) in the amlodipine group and -12.6 g/m2 (95% CI:
8.2, -17.0) in the lisinopril group. The higher the baseline value of left
ventricular mass before treatment, the more the decrease after treatment. Early
to atrial peak filling velocity did not change significantly within the treatment
groups: +0.07 (95% CI: -0.01, +0.15) in the amlodipine group and +0.01 (95% CI:
0.06, +0.08) in the lisinopril group. However, analysis of time measurements of
the early peak showed significant changes for both treatment groups. No
significant differences in primary and secondary endpoints between treatment
groups were found. Twelve patients did not complete the study, seven in
amlodipine and five in lisinopril, basically due to adverse events. The effects
of amlodipine and lisinopril on left ventricular mass and early to atrial filling
peak velocity after 1 year of treatment in patients with previously untreated
mild to moderate hypertension are similar. Further studies are recommended,
particularly with a larger sample size and a follow-up of longer duration.
PMID- 9657539
TI - Regression of left ventricular wall thickness during ACE-inhibitor treatment of
essential hypertension is associated with an increase in insulin mediated
skeletal muscle blood flow.
AB - Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a
condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE
inhibitors have been reported to be superior to most other antihypertensive drugs
in inducing a regression of LVH. In a double-blind study with parallel groups, 50
patients with essential hypertension were randomized to treatment with either
fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle
wall thickness (LVWT, defined as the sum of interventricular septum and posterior
wall), diastolic function (represented by the ratio between the E-wave and the A
wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated
using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h
of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in
FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in
ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol,
ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for
difference in treatment effect). However, only fosinopril treatment resulted in a
significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of
reduction in LVWT was related to the increase in FBF in the fosinopril group (r =
-0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive
relationship between the change in E/A ratio and the change in femoral artery
stroke volume (r = 0.80, p < 0.01). CONCLUSION: Impaired insulin-induced
stimulation of leg blood flow was related to an increased LVWT. Furthermore,
during fosinopril treatment, regression of LVWT was associated with enhanced
skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired
peripheral blood flow (and thereby increased afterload) may be a possible
mechanism explaining the previously found association between insulin resistance
and cardiovascular hypertrophy.
PMID- 9657540
TI - Video-assisted thoracoscopic excision of herniated thoracic disc: description of
technique and preliminary experience in the first 29 cases.
AB - This study evaluates the technique and results of video-assisted thoracoscopic
surgery (VATS) for the treatment of symptomatic thoracic disc herniation. Results
were compared with a literature review of open surgical techniques of thoracic
disc excision with regard to efficacy, safety, and surgical outcomes. VATS has
recently been described for thoracic surgery as having the advantage of decreased
postoperative pain and morbidity, faster patient recovery, and shortened
intensive care unit (ICU) hospitalization. Twenty-nine consecutive patients
underwent VATS for symptomatic thoracic disc herniation. Herniations ranging from
T5-6 to T12-L1 were successfully approached by using a three- or four-portal
strategy. Postoperative magnetic resonance imaging (MRI) scans were evaluated.
Pre- and postoperative Oswestry Disability Questionnaires and Linear Analog Pain
Scale data were obtained. Patients were grouped according to presenting symptoms.
The minimal follow-up was 1 year (range, 12-24 months). Mean operative time was
175 min for 29 patients. Significant improvement (p < 0.01, paired t test) was
recorded in Oswestry Disability Questionnaires and Linear Analog Scale Tests. Of
the patients, 75.8% (22) were satisfied, 3.4% (one) unsatisfied, with 20.1% (six)
unchanged. Narcotic use was significantly eliminated or reduced. Mean return to
work was 5 weeks (private insurance) and 21 weeks (workers compensation). The
surgical and postoperative complication rate was 13.8%. VATS appears to be a safe
and efficacious method of excising herniated thoracic discs. Follow-up results at
1 year resulted in high patient satisfaction. VATS advantages include decreased
length of hospitalization as well as improved patient comfort.
PMID- 9657541
TI - Neurologic deterioration after cervical spinal cord injury.
AB - Neurologic deterioration after cervical spinal cord injury (SCI) at a regional
spinal cord center was examined. This study examined the incidence of neurologic
deterioration as well as associated risk factors in our patient population. Up to
5.8% of cervical SCI patients have been noted to deteriorate neurologically after
admission. Risk factors have been early surgery, halo application, traction, and
Stryker frame rotation. All cervical SCI patients admitted between 1978 and 1993
who had neurologic deterioration were studied for characteristics of their event,
operative status, risk factors, mortality, and neurologic return at 1 year
postinjury. Patients were divided into minor and major groups based on the degree
of neurologic loss. Nineteen of 1,031 patients were identified as neurologically
deteriorated (1.84%). There were 8 major and 11 minor group patients. The average
time from injury to deterioration was 3.95 days. Of 10 patients undergoing
surgery at < or =5 days, 8 deteriorated postoperatively. Potential risk factors
were ankylosing spondylitis (three patients), sepsis (four patients), and
intubation (four patients). Neurologic recovery at 1 year showed that 11 of 12
patients were improved. Neurologic deterioration occurred in 1.84% of our
patients. Deteriorations were associated with surgery at <5 days after injury,
ankylosing spondylitis, sepsis, and intubation.
PMID- 9657542
TI - Accuracy of SPECT scanning in diagnosing pseudoarthrosis: a prospective study.
AB - The present study attempted to analyze the efficacy of single photon emission
computed tomography (SPECT) in diagnosing pseudoarthrosis after fusion using
surgical exploration as the gold standard. This study examined the SPECT scans of
38 patients before they underwent surgical exploration of their fusion mass for
suspected pseudoarthrosis or in conjunction with instrumentation removal.
Surgical findings were compared with the radiologists' findings to determine the
efficacy of SPECT in diagnosing pseudoarthrosis. Radiographic determination of
pseudoarthrosis has been difficult after attempted fusion of the spine. Multiple
radiographic modalities have been touted as accurate depicters of the failure of
spinal fusion. However, no method has been found to be highly accurate in the
clinical setting. Thirty-eight patients (mean age = 42.8, 21 males/17 females, 35
of 38 with instrumentation) underwent SPECT scans before surgical exploration of
their fusion mass for suspected pseudoarthrosis or in conjunction with
instrumentation removal as part of this prospective study. The average interval
from their fusion procedure until their SPECT scan was 23.9 months (range, 9-120
months). All surgical findings were recorded with regard to solidity of the
fusion and the level of the possible pseudoarthrosis. All SPECT scans were read
at a time after surgery by an independent nuclear radiologist who had not read
their SPECT scans before surgery and who did not know the results of exploration.
Results of the radiologist's reading were then compared with surgical exploration
findings, and sensitivity and specificity was calculated. There were 24 solid
fusions and 14 pseudoarthroses. SPECT scans correctly identified 7 of the 14
pseudoarthroses and 14 of the 24 solid fusions. This represents a sensitivity of
0.50 and a specificity of 0.58. SPECT scanning correctly diagnosed the one solid
fusion and two pseudoarthrosis patients in the three patients who had no
instrumentation. This study demonstrates that SPECT scanning alone is inaccurate
in diagnosing pseudoarthrosis when using surgical exploration as the gold
standard. Given recent pressures for cost containment, we cannot recommend SPECT
scanning as a routine modality for use in the diagnosis of pseudoarthrosis. We
cannot define the accuracy of SPECT scanning used together with computed
tomography scans, plain films, or other radiographic modalities in the diagnosis
of pseudoarthrosis.
PMID- 9657543
TI - Circumferential surgery for the management of cervical ossification of the
posterior longitudinal ligament.
AB - Can simultaneous anterior and posterior (circumferential) surgery in patients
with cervical ossification of the posterior longitudinal ligament
(OPLL)/stenosis, achieving both decompression and stabilization, be accomplished
with acceptable risk? Between 1989 and 1996, 22 circumferential procedures were
performed, including an average 2.5-level anterior corpectomy with 5-level
posterior wiring and fusion. These patients were severely myelopathic (average
Nurick grade 3.5) and were followed for a mean interval of 22 months (range 4-52
months). Circumferential procedures required an average of 9.8 h and 3.5 U of
blood transfused. Postoperatively, patients improved approximately +3.0 Nurick
grades. Simultaneous circumferential surgery for OPLL/stenosis may be
successfully performed in <10 h with limited blood loss.
PMID- 9657544
TI - Circumferential surgery for the management of cervical ossification of the
posterior longitudinal ligament.
PMID- 9657545
TI - Evaluation of computed tomographic methods to measure vertebral rotation in
adolescent idiopathic scoliosis: an intraobserver and interobserver analysis.
AB - The purpose of this study was to compare three computed tomography (CT)
measurement methods that have been described by Aaro-Dahlborn, Ho, and Krismer et
al. The methods were based on clinical, intraobserver, and interobserver
analysis. Twenty-five patients with adolescent idiopathic scoliosis were studied
for clinical reliability of these methods. There was a significant correlation
between Aaro-Dahlborn and Ho's methods (p < 0.02), and there was no correlation
between Krismer's method and the other two (p > 0.05). Intraobserver analysis was
performed by one observer at 20 different times, and interobserver analysis was
performed by 20 orthopedic surgeons on the same CT scan. Intraobserver and
interobserver analysis has shown that the method described by Ho is the most
reliable one. Consequently, Ho's method is the most reliable and clinically the
most useful method for measuring the vertebral rotation in adolescent idiopathic
scoliosis.
PMID- 9657546
TI - Biomechanical study of lumbar pedicle screws: does convergence affect axial
pullout strength?
AB - We tested the hypothesis that two pedicle screws placed in convergence offer more
resistance to axial pullout than do two pedicle screws placed in parallel. Eight
fresh cadaveric lumbar spines, L2-L5, were harvested. Individual vertebra were
then paired for testing. Into each L2 and L3 vertebra, a pair of pedicle screws
were inserted. The screws were placed parallel (i.e., at 0 degrees convergence)
in L2 and at 30 degrees convergence in L3, in the first pair. In the second pair
of L2 and L3, this order was reversed. Alternating the convergence angle was
carried out on each successive pair of L2 and L3. A section of standard
longitudinal rod was attached to each pedicle screw by using top-loading three
point shear clamp fixation with tangential lock screws. Transverse connectors
were attached superiorly and inferiorly to the longitudinal rods. As in L2 and
L3, each L4 and L5 received a pair of screws placed at either 0 or 30 degrees
convergence, with the angle of convergence alternated on each successive pair.
Each pair of screws in each vertebra was tested in axial pullout at 1 mm/s.
Fourteen pairs of vertebra were tested and two findings emerged: paired pedicle
screws at 30 degrees of convergence offered more resistance to axial pullout
(28.6% on average) and sustained higher loads at the clinical threshold of
loosening (101% on average) than paired pedicle screws placed in parallel. Thus
there seems to be an advantage to screws placed in 30 degrees of convergence as
compared with screws in parallel.
PMID- 9657547
TI - Effects of cross-linkage on fatigue life and failure modes of stainless steel
posterior spinal constructs.
AB - This study tested the effects of cross-linkage on the fatigue performance of
posterior spinal constructs (i.e., AcroMed stainless steel Isola systems). The
failure modes encountered during fatigue were also examined. The results of this
study confirmed earlier findings that the use of cross-linkage does not
significantly affect the stability of posterior constructs during axial loading.
Their influence in torsion loading is much more pronounced. During the fatigue
tests, posterior stainless steel spinal implants instrumented without cross
linkage reached 1 million cycles at 500- and 750-N loads. When the load was
increased to 1,000 N, the number of cycles to failure dropped by two-thirds.
These findings demonstrate that the endurance limit was between 750 N and 1,000 N
for spinal constructs without cross-linkage, with the limit being closer to 750
N. Devices equipped with one or two cross-linkages reached 1 million cycles at
500 N. The number of cycles to failure dropped dramatically as the load was
increased to 750 and 1,000 N. It appears that the endurance limits for spinal
devices using cross-linkage should be 500 and 750 N, with the limit closer to the
500-N load. All rod fractures occurred near the junction between the longitudinal
and transverse rods. Stress concentration was greatly in the vicinity of that
contact point. These results should provide a basis for future improvement in
endurance limits of spinal implants equipped with cross-linkage. Higher endurance
limits will reduce the toxic effects encountered during fracture modes. The
implants will also be better able to withstand the high physiologic loads
experienced by obese individuals.
PMID- 9657548
TI - Capsular ligament stretches during in vitro whiplash simulations.
AB - Clinical symptoms of whiplash are presently not well understood. Injuries to
capsular and other spinal ligaments of the cervical spine during trauma are a
possible pathomechanism that could explain some aspects of the whiplash symptom
complex. This study quantified the elongations of capsular ligaments (CLs) at all
cervical spinal levels during whiplash simulation using an in vitro model. Seven
fresh human cadaveric specimens (occiput-C7 or T1) were carefully dissected,
preserving the osteoligamentous structures. Spinal ligament transducers were
attached across the CLs from C2-C3 to C6-C7 in each specimen, alternating the two
sides. Physiological elongations of the CLs were measured with a standard
flexibility test using 1 Nm of pure moments. Next, the specimen was fitted with a
surrogate head representing 50th percentile human head. The specimen was mounted
on a sled designed to simulate whiplash and subjected to 2.5, 4.5, 6.5, 8.5, and
10.5 g (1 g = 9.81 m/s2) horizontal accelerations sequentially. The dynamic
elongations of the CLs were continuously recorded during the entire trauma and
were later converted to strains. There were modest increases in capsular ligament
strains during the trauma over the maximum physiological values. The two largest
peak strains of 29.5 and 35.4% were seen at C6-C7 during the 6.5- and 10.5-g
accelerations. We did not find strong correlation between the strain during the
trauma and the trauma sled acceleration.
PMID- 9657549
TI - Anatomic considerations of the vertebral artery: implications for anterior
decompression of the cervical spine.
AB - Anatomic dissection and measurements of the vertebral artery relative to the
medial margin of the longus colli and the anterior margin of the vertebral body
from C6 to C3 were performed in this study. The average angle of the vertebral
artery relative to the midline was 4.3 +/- 2.6 degrees overall. The average
distance between the medial margin of the longus colli and medial margin of the
vertebral artery gradually decreased from the C6 level (11.5 +/- 1.0 mm) to the
C3 level (9.0 +/- 1.3 mm). The average distance between anterior margin of the
vertebral body and anterior margin of the vertebral artery gradually increased
from the C6 level (7.2 +/- 1.9 mm) to the C3 level (9.6 +/- 2.1 mm). The distance
between medial borders of the longus colli muscles gradually decreased from the
C6 level (13.8 +/- 2.2 mm) to the C3 level (7.9 +/- 2.2 mm). Relative to the
medial margin of the longus colli muscle and the anterior margin of the vertebral
body, the vertebral artery is more lateral and anterior at the C6 level but more
medial and posterior at C3 level. This knowledge may facilitate effective
decompression of the lateral cervical canal and improve the margin of safety of
the surgeon.
PMID- 9657550
TI - Modified Magerl technique of lateral mass screw placement in the lower cervical
spine: an anatomic study.
AB - Twelve adult embalmed cadaveric cervical spines were used to modify the
traditional Magerl technique for screw placement in the lower cervical spine. The
starting point for the drill bit was 2 mm inferior to the inferiormost edge of
the superior facet and 1-2 mm medial to the posterior midline of the lateral
mass. The orientation of the drill bit was parallel to the superior facet in the
sagittal plane, and 25-30 degrees lateral in the transverse plane. After
drilling, we made direct measurements of the screw path length between the dorsal
and ventral cortexes of the lateral mass and screw-path angles in both the
sagittal and transverse planes. The results showed the mean screw-path length for
all levels ranged from 11 to 15 mm with the smallest value at C7. The mean
sagittal and transverse angles of the screw path ranged from 41 to 43 degrees and
from 26 to 28 degrees. Penetration of the superior facet was found in three
(2.5%) cases. Possible spinal nerve violation was seen in 13 (10.8%) cases if the
drill bit was excessively overpenetrated. This study suggested that our modified
Magerl technique for lateral mass screw placement be as high as possible without
impinging on the facet joint, and drilling be as cranial and lateral as possible
to leave the superior articular process as high and lateral as possible. This may
further decrease the incidence of spinal nerve injury. Careful drilling and
tapping technique is recommended to avoid overpenetration.
PMID- 9657551
TI - Finite element analysis of the lower lumbar neural arch under facet loading.
AB - To evaluate the mechanical effect of the direction of facet load on the isthmus
stresses of the lower lumbar neural arch, stress analyses were performed by using
three-dimensional finite element models of isolated L4 and L5 vertebrae with
particular emphasis on accurate discretization of the posterior elements. The
bilateral symmetric or unilateral facet loads, with a constant magnitude, were
applied within the sagittal and transverse planes. The largest maximal principal
stress in the neural arch (the largest sigma(max)) tended to be qualitatively
similar in L4 and L5. At the physiologic range, the largest sigma(max), observed
on the anterior surface of the isthmus, was relatively insensitive to the
sagittal plane loadings but sensitive to the transverse plane loadings. The
values of the largest sigma(max) of L4 and L5 were low at the more frontally
directed facet load. The magnitude and direction of the largest sigma(max)
depended upon the facet loadings mainly on the ipsilateral side and partly on the
opposite side. The results suggest that the direction of facet load, which may be
characterized by the facet orientation, can have mechanical effects on the
occurrence and direction of isthmic crack.
PMID- 9657552
TI - Nitric oxide: a possible etiologic factor in spinal cord cavitation.
AB - To determine whether nitric oxide (NO) is related to spinal cord cavitation, we
treated mice that underwent spinal cord injury with NG-mono-methyl-L-arginine (N
MMA). Spinal cord specimens were subjected to glial fibrillary acidic protein
(GFAP) immunostaining, which is selective for astrocytes. Spinal cord cavities
and GFAP-positive glial cells appeared simultaneously at 3 days after spinal cord
injury, and the cavities enlarged at 7 days. In mice receiving N-MMA, the
cavities were significantly smaller than those in the mice that underwent spinal
cord injury only. However, the numbers of GFAP-positive cells showed no
difference between these two groups. These experimental findings suggest that
cavitation of the spinal cord is caused mainly by NO released from activated
glial cells.
PMID- 9657553
TI - Proteoglycans in the nucleus pulposus of canine intervertebral discs after
chondroitinase ABC treatment.
AB - Experimental chemonucleolysis of the canine intervertebral disc with
chondroitinase ABC and chymopapain was compared during a 52-week period.
Roentgenograms and magnetic resonance imaging were used to examine changes in
disc space and water content, respectively. Disc space narrowing and reductions
in disc water content after chondroitinase ABC treatment were less than that
after chymopapain. High-performance liquid chromatography was performed to
measure changes in proteoglycans. Similarly to chymopapain, chondroitinase ABC
degrades proteoglycans in the nucleus pulposus and decreases their quantity.
However, large differences in the molecular weight and acidity of the
resynthesized proteoglycans and in the chain length of the resynthesized
glycosaminoglycans were observed between the two enzymes. The difference in disc
space narrowing and the changes in disc water content between the two enzymes
might result from differences in the characteristics of the resynthesized
proteoglycans.
PMID- 9657554
TI - Mechanical modulation of intervertebral disc thickness in growing rat tails.
AB - Progression of scoliosis deformity during growth is thought to be caused by
asymmetrical loading, resulting in asymmetrical growth with vertebral and disc
wedging in a "vicious cycle." The purpose of this study was to quantify the
changes in disc thickness during growth in rat tails subjected to compression or
distraction loading for 6 or 9 weeks, to investigate the hypothesis that disc
growth is mechanically modulated. Six-week-old Sprague-Dawley rats were studied
with compression loading (13 animals) or distraction loading (15 animals) applied
to their tails, and there were 8 sham animals. Loading was applied to tail
segments by means of an external ring fixator. Radiographic measurements of disc
thickness were made at biweekly intervals. From the initial to final radiograph,
compressed discs had reduced thickness averaging (+/-SD) 0.50 +/- 0.28 mm,
distraction discs had average increased thickness of 0.20 +/- 0.42 mm, and sham
discs lost an average of 0.21 +/- 0.18 mm of thickness (analysis of variance p <
0.001). There was an "initial change" in disc thickness averaging 0.18 +/- 0.32
mm in nonloaded discs, which was similar in magnitude to the elastic deformation
and was attributed to disc swelling under anesthesia. These results indicate that
growth in disc thickness is mechanically modulated by axial loading in growing
rats.
PMID- 9657555
TI - Cervical spondylitic myelopathy: plates in anterior recompression and
reconstruction.
PMID- 9657556
TI - Direct amplification of Mycobacterium tuberculosis deoxyribonucleic acid in
paucibacillary tuberculosis.
PMID- 9657557
TI - Pulmonary fibrosis: cytokines in the balance.
AB - Pulmonary fibrosis can complicate diverse pulmonary and systemic pathologies. In
many cases the underlying cause remains unidentified. Mortality from the disease
is increasing steadily in the UK and USA. The clinical features are well
described, but patients frequently present at an advanced stage, and current
treatments have not improved the poor prognosis. There is a compelling need to
identify the fibrotic process earlier and to develop new therapeutic agents.
Increased collagen deposition is central to the pathology and interest over the
last decade has focused on the role of cytokines in this process. These
polypeptide mediators are believed to be released from both circulating
inflammatory and resident lung cells in response to endothelial and epithelial
injury. Key cytokines currently implicated in the fibrotic process are
transforming growth factor-beta, tumour necrosis factor-alpha and endothelin-1.
This article outlines the evidence implicating these mediators in the
pathogenesis of pulmonary fibrosis and also considers the possible role of
cytokines with antifibrotic effects, such as interferon-gamma. The "balance" of
positively and negatively regulating cytokines is discussed, and the potential
for interaction with other factors including viruses, hormones and altered
antioxidant status is also considered. Finally, potential novel therapeutic
approaches are discussed, together with suggestions for future studies and
clinical trials. As the outcomes of different avenues of research over the last
ten years are brought together, it is clear that there is now a hitherto
unrivalled opportunity to begin to tackle the treatment of this devastating
disease.
PMID- 9657558
TI - Clinical utility of the polymerase chain reaction in the diagnosis of
extrapulmonary tuberculosis.
AB - This study examines the diagnostic utility of the polymerase chain reaction (PCR)
in 156 patients (five human immunodeficiency virus (HIV) seropositive) suspected
of extrapulmonary tuberculosis. The results of PCR in 226 samples from 11
different sites were compared with the results of microscopy and culture.
Positive culture results were predicted in 86% of samples by PCR but in only 31%
by microscopy. Specificity of PCR was 92%. In cases with culture-proven
tuberculosis, PCR identified all 11 microscopy positive cases and 19 of 24 (79%)
of the microscopy-negative cases. In four patients, PCR excluded the diagnosis of
tuberculosis in microscopy-positive samples, which were later shown to contain
mycobacteria other than Mycobacterium tuberculosis or laboratory contaminants. In
20 patients (microscopy, PCR and culture negative) a trial of antituberculous
drugs was given, but patients showed no improvement and treatment was stopped. In
17 patients, all culture negative (in nine PCR was positive, three of whom also
had positive microscopy) the diagnosis was probable tuberculosis based on
clinical findings and response to treatment. This polymerase chain reaction has a
much higher sensitivity than microscopy and can facilitate therapeutic decisions
for those with suspected extrapulmonary tuberculosis.
PMID- 9657559
TI - Analysis of BAL fluid in M. avium-intracellulare infection in individuals without
predisposing lung disease.
AB - The purpose of this study was to investigate the characteristics of pulmonary
inflammation caused by Mycobacterium avium-intracellulare (MAI) in individuals
with neither predisposing lung disease nor immunodeficiency. We reviewed the
records of 20 patients with pulmonary MAI infection (including 19 female
patients) whose past history and previous chest radiographs revealed no
predisposing lung disease. We analysed the bronchoalveolar lavage fluid (BALF)
from these 20 patients and from six normal female controls. The BALF was
recovered directly from the relevant segment that was identified with chest
computed tomography. The BALF cell profiles showed significantly elevated counts
for total cells, lymphocytes and neutrophils, but the macrophage cell count was
not elevated. The CD4+ lymphocyte count and CD4+/CD8+ ratio were significantly
increased compared with those in the controls. The lymphocytes demonstrated
phenotypical evidence of activation, with increased expression of human leukocyte
antigen-D-related antigen (HLA-DR). The tumour necrosis factor-alpha, interleukin
(IL)-1beta, IL-6 and IL-8 concentrations were significantly increased. The
neutrophil elastase concentration was also increased, and it was significantly
correlated with the neutrophil cell count in the BALF. These findings suggest
that the increased counts of activated CD4+ lymphocytes and neutrophils and the
elevated concentrations of proinflammatory cytokines and neutrophil elastase
appear to be common characteristics in Mycobacterium avium-intracellulare
infection.
PMID- 9657560
TI - Montelukast, a potent leukotriene receptor antagonist, causes dose-related
improvements in chronic asthma. Montelukast Asthma Study Group.
AB - The leukotrienes are known to be important mediators of bronchial asthma. The
ability of montelukast, a potent and selective CysLT1 leukotriene receptor
antagonist, to cause a dose-related improvement in chronic asthma was
investigated in a placebo-controlled, multicentre, parallel-group study. After a
two week placebo run-in period, chronic asthmatic patients with a forced
expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase
(absolute value) after beta2-agonist were randomly assigned to one of four
treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the
evening) for a three week, double-blind treatment period. For patient-reported
end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma
specific quality of life) and frequency of asthma exacerbations, montelukast 10
and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05;
linear trend test) different from placebo. All three doses caused improvements in
FEV1 and morning and evening peak expiratory flow rate (PEFR) that were
significantly (p<0.05) different from placebo. Differences (least square mean)
between the pooled 10 and 50 mg montelukast treatment groups and placebo were:
7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in
daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use
(puff x day(-1)). The incidence of adverse experiences was neither dose-related
nor different between montelukast and placebo treatments. We conclude that
montelukast causes a dose-related improvement in patient-reported asthma end
points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic
patients by improving asthma control end-points.
PMID- 9657561
TI - Effect of low-dose beclomethasone dipropionate on asthma control and airway
inflammation.
AB - The effects of usual or low doses of inhaled corticosteroids on airway mucosal
inflammation have not yet been examined. We therefore, compared the effects of
inhaled beclomethasone dipropionate (BDP) 336 microg x day(-1) on asthma control
outcomes and markers of airway inflammation. Twenty-four adult subjects with mild
and moderate asthma were randomized to receive either BDP or placebo for four
weeks; then subjects entered a single blind four week placebo run-in period. We
found that the BDP group had significantly greater improvements in forced
expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol
use than the placebo-treated group. The improvement in FEV1 largely reversed one
week after treatment was stopped. The decrease in the median percentage of
eosinophils in induced sputum in the BDP group from 3.8% to 3.4% was not
significant, but because eosinophils increased from 8.4% to 12.7% in the placebo
group, there was a significant difference between treatment groups (p=0.03).
There was no significant difference between groups during treatment in the levels
of eosinophil cationic protein (ECP), tryptase mucin-like glycoprotein, or
fibrinogen in induced sputum. The change in FEV1 in the BDP group did not
correlate significantly with the change in eosinophil percentage or ECP levels.
We concluded that four weeks of treatment with inhaled beclomethasone
dipropionate 336 microg x day(-1) was associated with significant improvements in
peak flow, forced expiratory volume in one second, and rescue salbutamol use in
asthmatic subjects but was not associated with large reductions in markers of
eosinophilic inflammation, bronchovascular permeability, or mucus hypersecretion.
PMID- 9657562
TI - Novel adaptation of a method to assess responsiveness of bronchial segments in
vitro.
AB - In vivo agonist delivery to the lungs is characterized by absorption through the
mucosal layer followed by access to the smooth muscle. When agonists are applied
to perfused bronchial segments, a difference in potency to agonists applied to
the serosal (outside) or mucosal (inside) surface can be demonstrated. In order
to elucidate this effect in canine bronchial segments, we adapted a method to
assess responsiveness of agonists applied to the inside or outside surface of
canine bronchial segments. A 2 cm "fluid-tight" length of bronchus was cannulated
and mounted in a perfusion chamber. Auxotonic contraction of the bronchus
displaced fluid inside the segment up a column and the change in height of fluid
within the column (afterload) was measured as a change in hydrostatic pressure
(volumetric). We assessed the optimal conditions for measuring bronchial
responsiveness to acetylcholine. Neither stretching segments lengthways from 100
to 140% of resting length, nor altering the transmural pressure from 3 to 21
cmH2O had a significant effect on the potency of acetylcholine applied to the
outside surface. Both acetylcholine (n=7) and methacholine (n=4) were
approximately 10-fold more potent when applied to the outside surface than the
inside surface of bronchial segments (p<0.0001). Furthermore, mechanical removal
of the epithelium (n=6) led to a 67-fold increase in potency of acetylcholine
applied to the inside surface compared with segments with epithelium. The
advantages that this system has over previously reported methods include: 1)
agonists can be injected at a low flow rate so as to minimize epithelial stress;
2) changes in luminal volume are measured under conditions of no flow; 3) after
load can be varied such that contraction is either practically isotonic or
auxotonic; and 4) a "barrier effect" of the epithelium of canine bronchial
segments can be demonstrated. This new adapted method will provide us with the
means to assess the relationship between in vitro and in vivo responsiveness in
human bronchi.
PMID- 9657563
TI - Upper airway cooling reduces upper airway resistance in anaesthetized young
guinea-pigs.
AB - In adults, the upper airway (UA) contains a variety of receptors including cold
receptors, which evoke reflex effects on ventilation and UA dilator muscle
activity, which may be important in the regulation of UA patency. However, very
little is known about UA receptors in young animals, and the effects of UA
cooling on UA dilator muscle activity and resistance have not been studied. A
constant flow of warm or cool air was applied to the isolated UA in
anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a
low-cervical tracheostomy while ventilation, UA resistance and geniohyoid muscle
electromyographic activity were recorded. Cooling caused an inhibition of
breathing, a reduction in UA resistance and an excitation of geniohyoid muscle
activity. Topical anaesthesia of the UA or sealing the nose and cutting the
superior laryngeal and glossopharyngeal nerves abolished the ventilatory and
geniohyoid muscle responses but not the fall in UA resistance. It is concluded
that upper airway cooling reflexly inhibits breathing and excites geniohyoid
muscle activity. Cooling also reduces upper airway resistance by an effect which
is not of reflex origin, possibly by reducing upper airway mucosal blood flow.
PMID- 9657564
TI - Specific immunotherapy downregulates peripheral blood CD4 and CD8 T-lymphocyte
activation in grass pollen-sensitive asthma.
AB - Several lines of evidence indicate that specific immunotherapy may act by
modifying the immune responses of T-lymphocytes to the antigen. To evaluate the
effect of specific immunotherapy on the activation of T-lymphocytes by cluster of
differentiation cells (CD4+ and CD8+) in peripheral blood, the expression of two
surface activation markers, the p55 interleukin-2 receptor (CD25) and human
leucocyte antigen (HLA)-DR, was studied prospectively on circulating CD4+ and
CD8+ T-cell subsets in subjects with grass-pollen sensitive asthma before and
after 1 yr of treatment with specific immunotherapy. Twenty five asthmatic
patients with pollen sensitivity other than grass, studied out of their pollen
season, served as the control group. Specific immunotherapy improved clinical
indices of disease activity including symptom scores and medication use during
the pollen season of the treatment year. It had a marked effect in reducing the
expression of the two activation markers, CD25 and HLA-DR, in both CD4+ (p=0.002
and p=0.005, respectively) and CD8+ (p=0.01 and p=0.01, respectively) T-cell
subsets, in parallel with a significant decrease in CD23 expression on B-cells
(p=0.008) and in grass-specific immunoglobulin E levels (p=0.01) in the
peripheral blood of subjects with grass pollen-sensitive asthma. The decreased T
lymphocyte activation observed in immunotherapy-treated subjects after the
treatment year was significant (p=0.05) in comparison with the control group.
These data add to the view that the efficacy of specific immunotherapy may be
attributed to the downregulation of T-cell responses.
PMID- 9657565
TI - Effects of orally inhaled budesonide in seasonal allergic rhinitis.
AB - It has previously been demonstrated that topical nasal treatment with
glucocorticosteroids has significant effects on the bronchial airways. Less is
known about effects on nasal disease by topical bronchial treatment with these
drugs. The present study examined effects on nasal allergic disease of inhaled
budesonide (avoiding nasal deposition of the drug). Patients with seasonal
allergic rhinitis, but without asthma, were thus given inhalations of budesonide
(600 microg b.i.d.) or placebo. The aim of the design was to allow the study of
eosinophilic airway disease in a part of the airway other than the directly
treated locus. Moderate to high birch pollen levels were recorded during the
study season, and nasal symptoms were significantly increased in both treatment
groups, although they were milder in patients receiving budesonide than in the
placebo group (p<0.05). Nasal brush eosinophils and nasal lavage fluid levels of
eosinophil cationic protein as well as blood eosinophils were increased during
the season (p<0.05), but these increases were prevented by the inhaled
budesonide. Nasal lavage fluid levels of alpha2-macroglobulin were particularly
elevated in the placebo group but did not differ between patients receiving
placebo and budesonide. Budesonide prevented the seasonal development of
increased bronchoconstrictor responses to methacholine challenge (p<0.05). In
conclusion, budesonide reduced the seasonal eosinophilia both in the circulation
and in the nose along with an attenuation of seasonal nasal symptoms. Hence, at a
daily dose of 600 microg b.i.d., known to cause no, or minimal, adverse effects,
inhaled budesonide produces clinically significant anti-inflammatory effects in
the entire airways, including the nasal mucosa, which is not exposed topically to
the drug. We suggest that nasal and systemic anti-eosinophil actions are produced
at commonly employed dose levels of orally inhaled budesonide.
PMID- 9657566
TI - Detection of immunoglobulins G and A to Aspergillus fumigatus by immunoblot
analysis for monitoring Aspergillus-induced lung diseases.
AB - The aim of the study was to investigate whether patients with Aspergillus-induced
lung disease can be monitored by immunoblot analysis to detect antibodies to
Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57
longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted
with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel
electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled
antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2
as substrate. The immunoblot patterns were related to the patients' clinical
status and time. Each patient had a characteristic immunoblot pattern that varied
with time. There was a relationship between disease activity or clinical response
and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA
antibodies was seen in sera collected during active disease, compared with before
active disease, and a significant decline in anti-Af IgG and IgA was demonstrated
in sera collected during recovery, compared with during active disease. Only in
the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies
against Af antigens of <20,000 Da demonstrated. Immunoblot analysis can be used
to monitor the disease activity and the responses to treatment of patients with
Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be
more informative than specific immunoglobulin G.
PMID- 9657567
TI - Role of interleukin-2 in the development and persistence of lymphocytic
alveolitis in farmer's lung.
AB - Farmer's lung (FL) is characterized by an intense lymphocytic alveolitis which
persists after an acute episode with continuous exposure to the offending
antigens. This study aimed to examine the role of interleukin-2 (IL-2) in the
development and persistence of this lymphocytic alveolitis. Three groups of dairy
farmers were studied: acute FL, ex-FL (past history of FL but no clinical
evidence of active disease) and asymptomatic farmers (no lung disease). IL-2 was
measured by enzyme immunosorbent assay and T-cell proliferation was evaluated by
3H-thymidine incorporation. Acute and ex-FL patients had more lymphocytes
(p<0.01) and higher levels of IL-2 (p<0.05) in their bronchoalveolar lavage (BAL)
than asymptomatic farmers. BAL T-lymphocytes from acute and ex-FL patients
released considerable amounts of IL-2 after stimulation with concanavalin A and
showed dose-dependent proliferative responses to IL-2. IL-2 production was
decreased after treatment with prednisone. Acute FL patients, but not ex-FL, had
higher levels of soluble CD25 in their serum than asymptomatics (p=0.009). These
results suggest that interleukin-2 may play a role in farmer's lung by providing
a stimulus not only for the accumulation of lymphocytes but also for their
persistence at the site of hypersensitivity reaction, and that the lung is a
likely source of this cytokine in vivo.
PMID- 9657568
TI - Six year longitudinal study of respiratory function in dairy farmers in the Doubs
province.
AB - A previous study, carried out in 1986 in France, showed the prevalence of
respiratory symptoms and of respiratory function impairment to be higher in dairy
farmers than in a control group of nonexposed subjects living in a rural zone. In
order to confirm the harmful effect of dairy farming, the two groups were re
studied 6 yrs later at the same period of the year. One hundred and ninety-four
(77.6%) farmers and 155 (62%) control subjects were available for re-examination.
Non-re-evaluated subjects were comparable to re-evaluated subjects for age, sex,
smoking and respiratory symptoms and function at initial evaluation. Dairy
farmers consistently had more respiratory symptoms and lower levels of
respiratory function than did control subjects. In the study populations as a
whole, the mean annual decline in vital capacity (VC) and forced expiratory
volume in one second (FEV1) was slightly, but nonsignificantly, higher in farmers
than in control subjects: in mL x yr(-1) (SD), -43.1 (68.2) versus -37.9 (60.2)
for VC and -32.8 (56.7) versus -30 (47.2) for FEV1. There was a positive
interaction between farming and age (i.e. duration of exposure in this cohort) on
respiratory function decline, and in male subjects aged > or = 45 yrs, dairy
farming was associated with an accelerated loss in VC (p<0.05) and FEV1 (p<0.05)
after controlling for age, smoking, height and geographic location in a multiple
linear regression model. Initial values of respiratory function, age and pack
years smoked (only for VC) were the other variables found to be significant
determinants of decline in lung function. In conclusion, this study mainly
suggests that dairy farming is associated to a very moderate accelerated loss in
respiratory function that increases with duration of exposure and is significant
in older male subjects.
PMID- 9657570
TI - Acid fog and hospital visits for asthma: an epidemiological study.
AB - The aim of this study was to elucidate the adverse respiratory effects of
naturally occurring acid fog. In total, 102 adult asthmatic patients (44
nonatopic and 58 atopic) were studied for a 2 yr period (January 1992 to December
1993) in Kushiro, a city with only a small industrial area, located in the
northern-most island in Japan. Fog occurred on 378 out of 731 days, and the
acidity of the fog ranged from pH 3.32 to 6.91 (mean pH 4.95). The association
between hospital visits for asthma and meteorological factors or air pollutants
was investigated. In nonatopic patients, fog, high ozone and water vapour
pressure, low day-to-day temperature differences, low concentrations of
atmospheric NO and NO2 contributed significantly (p<0.05) to increasing hospital
visits. In atopic subjects, fog, high water vapour pressure, low levels of
atmospheric NO2 and SO2 contributed significantly to hospital visits (p<0.05). In
Poisson regression analysis the remaining factors of significance (p<0.01) for
nonatopic asthma were fog and low NO and for atopic asthma were high water vapour
pressure and low SO2 (p<0.05). A weak but significant correlation was observed
between the number of hospital visits and the mean pH of the foggy day (r=-0.38,
p<0.05) in nonatopic asthmatic patients, not in atopic asthma. On foggy days,
gaseous air pollutant levels were significantly (p<0.01) lower than on fog-free
days. It was concluded that, naturally occurring acid fog may have a weak
bronchoconstrictive effect which appears to be more influential in nonatopic
asthmatic subjects than in atopic subjects.
PMID- 9657569
TI - Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage
fluid and bronchial mucosa of healthy subjects.
AB - Short-term exposure to ozone at peak ambient levels induces neutrophil influx and
impairs lung function in healthy humans. In order to investigate the mechanisms
contributing to neutrophil recruitment and to examine the role of T-cells in the
acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per
million (ppm) of ozone and filtered air on two separate occasions for 2 h with
intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)).
Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total
protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth
related oncogene-alpha (Gro-alpha) were measured and total and differential cell
counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was
performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and
gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets
(CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell
numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion
molecules including P-selectin, E-selectin, intercellular adhesion molecule
(ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial
biopsies. Paired samples were available from nine subjects. Following ozone
exposure there was a threefold increase in the proportion of polymorphonuclear
neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was
accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and
total protein (p=0.058). A significant positive correlation was demonstrated
between the two chemokines and proportion of PMNs in BAL fluid. After ozone
exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the
proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no
significant changes were demonstrable in any of the inflammatory markers studied
in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a
neutrophil influx in peripheral airways at 6 h post exposure, but no apparent
inflammatory response in proximal airways. This response seems to be mediated at
least in part by interleukin-8 and growth-related oncogene-alpha.
PMID- 9657571
TI - Association between PM10 and decrements in peak expiratory flow rates in
children: reanalysis of data from five panel studies.
AB - Panel studies have found 1-3% increases in reports of acute respiratory symptoms
associated with each 10 microg x m(-3) increase in ambient concentrations of
particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10).
Statistically significant decrements in population mean peak expiratory flow
(PEF) have also been observed but their magnitude is only about 0.1% for the same
exposure. This study evaluated whether this difference is due to the different
measurement scales used for the expression of the effects of air pollution on PEF
and respiratory symptoms. The association between the prevalence of large
decrements in PEF (more than 10% or 20% below the median) and PM10 concentrations
was analysed using data from five recent panel studies. The effect estimates were
compared to the effect estimates from original studies based on the population
mean PEF. The decrement in the population mean PEF for an increase of 10 microg x
m(-3) of the same-day PM10 concentration was 0.07%, averaged over all panels. A
significant relative increase of 2.7% (95% confidence interval 1.6-3.8) in the
prevalence of PEF decrements greater than 10% was associated with the same
exposure. In conclusion, defining the peak expiratory flow response by the
prevalence of large decrements provides effect estimates of a comparable
magnitude to effect estimates for the prevalence of reports of acute lower
respiratory symptoms.
PMID- 9657572
TI - Effects of air quality on chronic respiratory symptoms adjusted for allergy among
preadolescent children.
AB - The aim of this study was to assess the respiratory effects of outdoor air
pollution after correcting for allergy and indoor air quality. The respiratory
health survey targeted 1,129 schoolchildren, 9 yrs of age, attending schools in
Krakow located in city areas differing in outdoor air pollution levels. Chronic
phlegm as a unique symptom was related neither to allergy nor to indoor
variables, but was associated with the outdoor air pollution level (odds ratio
(OR): 4.2; 95% confidence interval (CI): 1.1-16.9). The same relationship has
been confirmed for the self-reported local sources of industrial air pollution in
the area of residence (OR: 4.2; 95% CI: 1.5-11.7). Hay fever appeared to be
related to outdoor air pollution level (OR: 1.43; 95% CI: 1.1-2.0) and self
reported heavy traffic (OR: 1.3; 95% CI: 1.0-1.7). In the total sample, wheezing
was connected exclusively to allergy and parental atopy, while attacks of
dyspnoea with wheezing and asthma diagnosed by physician only were associated
with allergy. Since the effect of outdoor pollutants on chronic cough and
wheezing (odds ratio: 1.85; 95% confidence interval: 1.03-3.33) was only shown to
be significant in the subsample of children without allergy and parental atopy,
it may be postulated that either allergy is predisposing to respiratory
reactions, or outdoor air pollution is coinvolved in an allergization process of
the preadolescent children. Consequently, allergy should be considered as an
important confound in epidemiological studies on the respiratory effects of air
pollution.
PMID- 9657573
TI - Effect of environmental tobacco smoke on cough in children with a history of
tonsillectomy or adenoidectomy.
AB - We examined the possible impact of tonsillectomy or adenoidectomy (T/A) on the
relationship between environmental tobacco smoke (ETS) exposure and respiratory
outcomes. This study was conducted in Humboldt, Saskatchewan, in 1993. The target
population included all residents aged 6-17 yrs. Of the 1,019 eligible subjects,
892 participated (88%). Estimates of ETS exposure were based on the reported
smoking habits of the children's household members. We defined current cough as a
positive response to the question: "Does this child usually have a cough?".
Information also included morning cough, night cough and a history of T/A. For
children with no history of T/A, the prevalence of current cough was 8.9%, 12.2%
and 14.5% for those living in families with 0, 1, and 2+ smokers respectively.
The corresponding prevalence was 7.0%, 30.2% and 36.8% for children with history
of T/A. Similar effects of ETS exposure were observed on morning cough and night
cough. The results did not change significantly when we used various ETS measures
and controlled for confounding factors. Compared to children living in nonsmoking
families and without history of T/A, the adjusted odds ratio for children with a
history of T/A was 7.19 (p<0.001) if they were living in families smoking >20
cigarettes x day(-1) at home. The corresponding odds ratio was only 1.64 (p=0.11)
for children without a history of T/A. We concluded that children living in
smoking family were more likely to cough than those living in nonsmoking families
and tonsillectomy or adenoidectomy increased the apparent influence of
environmental tobacco exposure on cough.
PMID- 9657574
TI - Increasing prevalence of wheeze and asthma in Nottingham primary schoolchildren
1988-1995.
AB - The prevalence of asthma in children has increased substantially in many
countries in recent decades, but it is not clear how much this trend has
continued into the 1990s. This study aimed to estimate the current prevalence of
asthma and wheeze in British primary schoolchildren and to determine whether
there has been any increase in the prevalence of these conditions since 1988. The
prevalence of self-reported wheeze and asthma was measured by parental
questionnaire in 22,968 children aged 4-11 yrs attending primary schools in the
Nottingham area of England in 1995, and these estimates were compared with data
from a subsample of the same schools in 1988. In 1995, wheezing ever was reported
in 24.0% of children, wheezing in the past year in 15.1% and diagnosed asthma
symptomatic in the past year in 8.8%. All measures have increased in prevalence
since 1988, in absolute terms by 7.7% for wheeze ever, by 2.6% for wheeze in the
past year and by 2.7% for asthma. The increases were greater in females than
males, but did not vary with age. In conclusion, the prevalence of asthma has
continued to rise in British schoolchildren since the late 1980s, particularly in
females, and across all ages.
PMID- 9657575
TI - Expression of insulin-like growth factors and their binding proteins by
bronchoalveolar cells from children with and without interstitial lung disease.
AB - The involvement of the insulin-like growth factor (IGF) system in lung growth and
repair following injury is sustained by a number of studies. Based on this
knowledge, the aim of the present work was to document the expression of the IGFs
and their binding proteins by alveolar cells obtained by bronchoalveolar lavage
(BAL). Two groups were investigated: a control group of five children and a group
of 11 children referred to the department for exploration of interstitial lung
disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and
IGF-binding proteins (IGFBP). Expression of these factors was analysed at the
level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse
transcription polymerase chain reaction techniques), and of protein for the
IGFBPs. In addition, expression of two major cytokines associated with the
inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming
growth factor-beta (TGF-beta), was also documented. In children without
parenchymal disease, the growth factor expressed was IGF-I, in association with
the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression
of IGF-I was observed in nine patients and of IGF-II in three patients, and the
presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins).
Evaluation of IGFBP-2 expression indicated an increase in the group of children
with ILD. Interestingly, a significant association was observed between the
increase in IGFBP-2 expression and TGF-beta expression. The present data
emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL
of all patients, and suggest that this protein may be an important factor of the
injury/repair processes during the progression of alveolar inflammation.
PMID- 9657576
TI - Effects of formoterol, salmeterol or oxitropium bromide on airway responses to
salbutamol in COPD.
AB - We examined whether a pretreatment with formoterol, oxitropium bromide, or
salmeterol might modify the dose-response curves to inhaled salbutamol in
patients with stable and partially reversible chronic obstructive pulmonary
disease (COPD). Sixteen outpatients with partially reversible, stable COPD
received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium
bromide, or placebo on four non-consecutive days. Spirometric testing was
performed immediately before inhalation of treatment and after 2 h. A dose
response curve to inhaled salbutamol was then constructed using doses of 100,
100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg.
Dose increments were given at 20 min intervals with measurements being made 15
min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a
significant increase in forced expiratory volume in one second (FEV1) compared
with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol
0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean
values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and
800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41,
1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27,
1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences
in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy
with formoterol, salmeterol, or oxitropium bromide compared with placebo. This
study clearly shows that a pretreatment with a conventional dose of formoterol,
salmeterol, or oxitropium bromide does not preclude the possibility of inducing a
further bronchodilation with salbutamol in patients suffering from partially
reversible chronic obstructive pulmonary disease.
PMID- 9657577
TI - Deposition and clearance of inhaled 18FDG powder in patients with chronic
obstructive pulmonary disease.
AB - As freon is limited in its use as a generator for aerosol inhalation, powder
particles are used as an alternative for inhalation therapy. The pulmonary
deposition and clearance of inhaled powder particles was studied by positron
emission tomography (PET) in ten patients with chronic obstructive pulmonary
disease (COPD) and in five normal controls. The powder, 5 microm in mean
diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose
(18FDG). Powder inhalation was done with single deep inspiration from residual
volume to total lung capacity. The initial deposition ratio in the right or left
lung field to total inhaled dose, measured by an anteroposterior rectilinear
scan, did not differ between normals and COPD patients. Ratios of radioactivity
detected within the central and peripheral regions (the central to peripheral
ratio) measured by the PET scan was not significantly different between COPD
patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the
regional powder deposition in peripheral lung fields measured by the PET scan was
significantly more uneven in COPD patients than in normal patients. The clearance
rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially
deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi
or peripheral lung fields measured by tomographic scan showed a wider variation
in COPD patients than in normals. To conclude, inhaled powder tended to be
deposited more centrally and was distributed more unevenly in the peripheral lung
in chronic obstructive pulmonary disease patients than in normals. This could be
a limitation of powder inhalation used for therapy in chronic obstructive
pulmonary disease patients.
PMID- 9657578
TI - Noninvasive pressure support ventilation in COPD patients with postextubation
hypercapnic respiratory insufficiency.
AB - Patients with chronic obstructive pulmonary disease (COPD) who have been
intubated and mechanically ventilated may prove difficult to wean. Noninvasive
ventilation may be used in an attempt to avoid new endotracheal intubation. The
efficacy of administration of noninvasive pressure support ventilation was
evaluated in 30 COPD patients with postextubation hypercapnic respiratory
insufficiency, compared with 30 historically matched control patients who were
treated conventionally. Patients were included in the study if, within 72 h
postextubation, they presented with respiratory distress, defined as the
combination of a respiratory frequency >25 breaths x min(-1), an increase in the
arterial carbon dioxide tension (Pa,CO2) of at least 20% compared with the value
measured after extubation, and a pH <7.35. Noninvasive pressure support
ventilation was effective in correcting gas exchange abnormalities. The use of
noninvasive ventilation significantly reduced the need for endotracheal
intubation: 20 of the 30 patients (67%) in the control group required
endotracheal intubation, compared with only six of the 30 patients (20%) in the
noninvasive-ventilation group (p<0.001). In-hospital mortality was not
significantly different between the two groups, but the mean duration of
ventilatory assistance for the treatment of the postextubation distress, and the
length of intensive care unit stay related to this event, were both significantly
shortened by noninvasive ventilation (p<0.01). In conclusion, noninvasive
ventilation may be used in the management of patients with chronic obstructive
pulmonary disease and postextubation hypercapnic respiratory insufficiency.
PMID- 9657579
TI - References values for forced spirometry. Group of the European Community
Respiratory Health Survey.
AB - The European Coal and Steel Community (ECSC) prediction equations exemplify a
significant effort carried out approximately 15 yrs ago to provide uniform
standards for lung function testing, but this set of equations has not been
properly validated as yet. The present study evaluates the ECSC reference values
and four other sets of prediction equations, using spirometric data collected in
12,900 nonasthmatic subjects (43% lifetime nonsmokers and 36% active smokers)
aged 20-44 yrs from the European Community Respiratory Health Survey (ECRHS).
Standardized spirometric measurements were obtained using a common protocol in 34
centres in 14 countries. For each prediction equation, the prediction deviations
(i.e. observed minus predicted value) for forced vital capacity (FVC) and forced
expiratory volume in one second (FEV1) were examined for the whole study
population and for each centre. For the age range included, the errors about the
ECSC equations showed the most prominent underestimation of both predicted FVC
(+355 and +360 mL on average in males and females, respectively) and predicted
FEV1 (+211 and +200 mL, respectively) among the five studies examined. As
expected, FVC and FEV1 in active smokers from the ECRHS were significantly lower
than in lifetime nonsmokers (each p<0.01). We conclude that the present European
recommendations on lung function reference values should be reconsidered, but
further data for nonsymptomatic subjects above the age of 44 yrs are needed.
PMID- 9657580
TI - Respiratory symptoms, lung function and use of health services among unemployed
young adults in Spain. Spanish Group of the European Community Respiratory Health
Survey.
AB - The association of respiratory symptoms, lung function and use of health services
with employment status was examined in Spain, a country with a high rate of
unemployment. A population sample comprising 179 unemployed and 1,868 employed
subjects aged 20-44 yrs in 1993, was randomly selected from a base population of
about 170,000 people in five urban and rural areas of Spain. Subjects completed a
questionnaire on respiratory symptoms, sociodemographic and lifestyle factors,
occupational exposure and use of health services, and performed a forced
spirometry, a methacholine challenge test and blood tests. Unemployed subjects
had a higher risk of simple chronic bronchitis (odds ratio=2.06, 95% confidence
interval 1.30-3.24) and of bronchitis-type symptoms, than those who were
employed. These risks were, in part, due to the higher prevalence of smoking,
poorer housing and prior occupational exposures among unemployed than among
employed people. Smaller differences were found between employed and unemployed
subjects for asthma-type symptoms, atopia and lung function tests. Use of health
services among subjects with respiratory symptoms was similar among employed and
unemployed subjects, except that the latter consistently reported less frequent
contact with specialized practitioners. Unemployed subjects had a higher risk of
bronchitis-type symptoms than employed subjects. In Spain's national, free-access
healthcare system, the differential use of specialized health services by
employment status is likely to imply differences in the characteristics of the
healthcare provided.
PMID- 9657581
TI - Relationship between external resistances, lung function changes and maximal
exercise capacity.
AB - In upper airway obstruction (UAO) the relationship between the degree of
obstruction, exercise limitation and lung function indices is not well
established. Therefore, we investigated in nine healthy subjects (age 36+/-9 yrs)
the effects of two added resistances at the mouth (R1 = added resistance with 7.8
mm diameter; R2 = 5.7 mm) on forced expiratory volume in one second (FEV1), peak
expiratory flow (PEF), airway resistance (Raw) and maximal breathing capacity
(measured during 15 s = measured maximum breathing capacity (MBCm); calculated as
FEV1x37.5 = calculated maximum breathing capacity (MBCc)) on the one hand, and
maximum exercise capacity (W'max), minute ventilation (V'E) and CO2 elimination
(V'CO2) on the other. We found that R1 had almost no influence on FEV1 but
decreased PEF by approximately 35% and increased Raw by almost 300%; it decreased
W'max by merely approximately 10% while maximal exercise ventilation (V'Emax) was
only 65% of control and only reached approximately 40% MBCc and approximately 70%
MBCm; yet V'E and V'CO2 were significantly reduced at high exercise levels
indicating hypoventilation. With R2, FEV1 was reduced by 25% and PEF by 55%, and
Raw was increased by 600%; W'max was approximately 60% of control, V'Emax was
only 35% of control and reached approximately 30% MBCc and approximately 60%
MBCm, V'E was already reduced at moderate exercise levels. We conclude that: 1)
an upper airway obstruction of 6 mm diameter (but not of 8 mm) had a marked
influence on maximum exercise capacity due to hypoventilation; 2) calculated
maximum breathing capacity markedly overestimated measured maximum breathing
capacity because the forced expiratory volume in one second is an insensitive
index of upper airway obstruction and because it does not take inspiratory flow
limitation into account; and 3) a 10% decrease in maximum exercise capacity was
linearly related with a 7% decrease in the forced expiratory volume in one second
and a 150% increase in airway resistance. A 10% decrease in maximal exercise
ventilation was related to a 8.5% decrease in peak expiratory flow and 9%
decrease in measured maximum breathing capacity.
PMID- 9657582
TI - The effect of octreotide on breathing and the ventilatory response to CO2 in
conscious dogs.
AB - It has been reported that injection of somatostatin into the brain-stem will lead
to apnoea in animals. The aim of this study was to determine whether peripheral
administration of octreotide, an analogue of somatostatin, could influence the
control of breathing. We measured the tidal volume, respiratory rate and
ventilatory response to CO2, before and after the intravenous injection of two
dose levels of octreotide (0.1 mg and 0.5 mg) or saline in four conscious adult
dogs. Injection of octreotide altered the breathing pattern with a mean decrease
in the respiratory frequency of 23% (p<0.05) and an increase in the tidal volume
by 16% (p<0.05), resulting in no net change in ventilation. The normal value of
the ventilatory response to CO2 ranged between 1.0-3.2 L x min(-1) x mmHg(-1),
with a minor variance within each dog but a significant difference amongst the
four dogs (p<0.05). No significant change in the ventilatory response to CO2 was
observed after octreotide. We conclude that intravenous octreotide alters the
pattern of breathing but preserves minute ventilation; peripheral administration
of octreotide does not influence the ventilatory response to CO2.
PMID- 9657583
TI - Expiratory valves used for home devices: experimental and clinical comparison.
AB - A bench study followed by a clinical trial were performed to evaluate the
mechanical characteristics of five (commercially available) expiratory valves
used for home ventilators, as well as the potential clinical impact of
differences between these valves. In the in vitro study, expiratory valve
resistance was evaluated under unvarying conditions, whereas dynamic behaviour
was evaluated by calculating the imposed expiratory work of breathing during a
simulated breath generated by a lung model. Differences in resistance and imposed
expiratory work of up to twofold and 150%, respectively, were found across
valves. We then conducted a randomized crossover clinical study to compare the
effects of the least resistive (Bennett) and most resistive expiratory valves
(Peters) in 10 intubated patients receiving pressure support ventilation. There
were no significant differences regarding blood gases or respiratory parameters
except for the oesophageal pressure-time product (PTPoes), which was
significantly increased by the Peters valve (236+/-113 cmH2O x s x min(-1) versus
194+/-90 cmH2O x s x min(-1)). An analysis of individual responses found that the
Peters valve induced substantial increases in intrinsic positive end-expiratory
pressure (PEEP), PTPoes, and expiratory activity in those patients with the
greatest ventilatory demand. In conclusion, differences between home expiratory
valve resistances may have a clinically relevant impact on the respiratory effort
of patients with a high ventilatory demand.
PMID- 9657584
TI - Airway response of children with primary ciliary dyskinesia to exercise and beta2
agonist challenge.
AB - In primary ciliary dyskinesia (PCD), chest physiotherapy for airway clearance is
essential. Exercise and inhaled beta2-agonists can produce bronchodilation
thereby augmenting physiotherapy. However, both can also cause
bronchoconstriction, and the effects of these stimuli in PCD are not known. In a
preliminary study, the mean coefficients of variation for forced expiratory
volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow
rate (PEFR) in children with PCD were determined. They were 5.4%, 4.4% and 8.4%,
respectively. Twelve children with PCD and 12 normal children performed pulmonary
functions under resting conditions; during and after a validated treadmill
exercise test; and before and 15 min after 200 microg of inhaled salbutamol. At
baseline, FEV1, FVC, forced mid-expiratory flow (FEF25-75%) and PEFR were
significantly reduced in the PCD group compared with the control group. Exercise
produced a significant increase in PEFR in the PCD group. There was no
significant difference between the groups in response to salbutamol. Within the
PCD group, exercise produced a significantly greater increase in PEFR than beta2
agonist therapy. In conclusion, in children with primary ciliary dyskinesia there
is evidence of obstructive pulmonary disease. In these children, exercise is a
more potent stimulus for bronchodilation than by inhaled beta2-agonists.
Enhancement of airway clearance may best be achieved by encouraging patients to
exercise before physiotherapy rather than by inhaling beta2-agonists, but the
effects of each should be assessed for each individual before instigating
treatment.
PMID- 9657585
TI - Magnetic resonance (MR) imaging of the chest: state-of-the-art.
AB - To date, magnetic resonance (MR) is established as an imaging modality in the
diagnosis of chest diseases. Because of its excellent distinction of vessels and
soft tissue, MR can be performed as the primary imaging procedure before computed
tomography in patients with suspected vascular lesions, mediastinal masses, hilar
lesions, and pathological changes of the pleura and the chest wall. In these
cases, MR is able to provide all the necessary diagnostic information. In other
patients, a limited number of MR images may be helpful in cases of equivocal or
confusing CT or clinical findings. More detailed information can be obtained,
using surface coils or special imaging sequences, i.e. high resolution MR images
of the pleura or angiographic images of mediastinal and pulmonary vasculature.
From a clinical viewpoint, the most important task for thoracic magnetic
resonance nowadays is the pretherapeutic evaluation of intrathoracic masses, the
differential diagnosis of benign versus malignant lesions, and the accurate
documentation of tumour extent in malignancies including three-dimensional
display to improve surgical or radiation planning. Future directions in thoracic
magnetic resonance will be predominantly influenced by postprocessing approaches,
specialized imaging techniques, and magnetic resonance-guided interventional
applications.
PMID- 9657586
TI - Serial sputum cell counts in the management of chronic airflow limitation.
AB - This case study illustrates the usefulness of serial induced sputum cell counts
from cytospins to investigate the nature of airway inflammation in a patient
presumed to have prednisone-dependent asthma for 30 yrs. She had bronchiectasis
and chronic airflow limitation. Exacerbations of breathlessness were associated
with an increase in chronic airflow limitation with little or no sputum. Induced
sputum showed elevated total cell and neutrophil counts at each exacerbation with
no increase in the proportion of eosinophils. Pathogenic bacteria were cultured
at each flare-up. The dose of prednisone was reduced progressively and each
exacerbation was treated with an appropriate antibiotic without increasing the
dose of prednisone, as was the case previously. The infections were associated
with bronchiectasis of the right upper lobe which was removed. Examination of the
specimen confirmed neutrophilic infiltration and did not show the usual airway
structural changes of asthma. These results provide further evidence of the value
of sputum cell counts in practice, in this case to prevent overtreatment with
prednisone in a patient with recurrent deteriorations in airflow which were due
to recurrent infections.
PMID- 9657587
TI - Lung abscess complicating chondromas in Carney's syndrome.
AB - Carney's syndrome consists of a combination of three rare tumours: gastric
leiomyosarcoma, pulmonary chondroma and catecholamine-secreting paraganglioma. We
describe a young woman with Carney's syndrome, who developed a lung abscess, due
to obstruction of a bronchus by a chondroma, 11 yrs after having had a partial
gastrectomy for a leiomyosarcoma.
PMID- 9657588
TI - Interstitial lung disease more than 40 years after a 5 year occupational exposure
to talc.
AB - A 62 yr old woman was initially diagnosed with sarcoidosis until a thoracoscopic
biopsy revealed the presence of numerous birefringent particles in fibrotic areas
of the centrilobular lung zones. These particles were examined by electron
microscopy and X-ray spectrometry and characterized as impure talc. Further
inquiry into her occupational history revealed that she had worked from the age
of 14-18 yrs in a factory making rubber hoses, where she had had an intense
exposure to talc. There was no evidence of silicosis or asbestosis, and other
significant causes of interstitial lung disease were excluded. This case
emphasizes the importance of a thorough occupational history, which may reveal a
remote and forgotten exposure to a significant cause of interstitial lung
disease. Although this presentation of talcosis is unusual, this case suggests
that even a relatively short, but presumably intense exposure to talc more than
40 yrs previously may be a cause of progressive lung fibrosis.
PMID- 9657589
TI - Guidelines for mineral fibre analyses in biological samples: report of the ERS
Working Group. European Respiratory Society.
AB - Microscopic techniques for analysing asbestos fibres in lung tissue and
bronchoalveolar lavage have provided major information in the understanding of
asbestos-related diseases. These analyses are increasingly applied for clinical
work and medicolegal problems. Differences in sampling, preparation and counting
techniques, definitions of reference populations and expression of results have
caused major difficulties in comparing results from different laboratories.
Therefore it appeared necessary to set a goal to harmonize these analyses between
the European laboratories active in this field. This article summarizes the work
of a European Respiratory Society working group with participation from nine
European laboratories. The five main issues touched upon are: 1) definitions of
control populations and reference levels; 2) sampling, preparation and analytical
techniques; 3) asbestos fibres in lung tissues in different pathologies; 4)
asbestos bodies in lung tissue, bronchoalveolar lavage and sputum; and 5) basis
for the interpretation of fibres and asbestos bodies in biological samples. These
guidelines indicate the crucial importance of several factors for the
interpretation of the results; namely, adequate sampling, comparable analytical
procedures and expression of the results, the use of well-defined reference
populations, and a comprehensive understanding of the factors affecting the fibre
retention and the dose-responses associated with the different asbestos-related
diseases.
PMID- 9657590
TI - Asbestos, ergot drugs and the pleura.
PMID- 9657591
TI - Macrolide antibiotics in diffuse panbronchiolitis and in cystic fibrosis.
PMID- 9657593
TI - Analysis of blood chemistry and hearing levels in a sample of older persons.
AB - OBJECTIVE: As part of an ongoing study of presbyacusis, the relationship between
blood chemistry levels and hearing levels was investigated. Previous reports
often used small sets of blood chemistry measures, and results were inconclusive.
This experiment examined hearing levels and 27 measures of blood chemistry using
various univariate and multivariate statistical procedures. DESIGN: Blood from 89
female and 128 male human subjects was collected. Subjects' ages ranged from 60
to 82 yr, and hearing levels ranged from normal to moderate/severe. Subjects with
a history of middle ear disease were excluded. Electrolyte panel (Na, K, Cl, CO2,
Ca, urea nitrogen, glucose, creatinine, and Mg), hematology panel (WBC, RBC, Hgb,
hematocrit, platelet, etc.), serum lipids (total cholesterol, low-density
lipoprotein [LDL], and high-density lipoprotein [HDL]), immunoglobulins (IgG,
IgA, IgM, and IgE), and thyroxine were analyzed using univariate and multivariate
statistical procedures. RESULTS: Blood chemistry levels of most subjects were
within normal ranges as defined by our laboratory. Correlation between blood
chemistry measures and pure-tone averages (PTAs) ranged from minimal to low.
Results of factor analysis, discriminant analysis, and canonical analysis showed
that combining blood chemistry measures from the same panel still could not
predict PTA effectively. One exception to this was a gender-specific effect of
cholesterol. Hearing levels of women with high LDL/HDL ratios were 5 dB better
than those of women with low LDL/HDL ratios. The comparable difference in men was
only 1 dB. CONCLUSION: Results suggest that blood chemistry measures that are
primarily within the normal range have very little value in predicting pure-tone
thresholds in older subjects.
PMID- 9657592
TI - Transient deafness due to temperature-sensitive auditory neuropathy.
AB - OBJECTIVE: To define mechanisms accounting for transient deafness in three
children (two siblings, ages 3 and 6, and an unrelated child, age 15) when they
become febrile. DESIGN: Audiometric tests (pure-tone audiometry, speech and
sentence comprehension), tympanometry, middle ear muscle reflex thresholds,
otoacoustic emissions (OAEs), and electrophysiological methods (auditory brain
stem responses [ABRs], sensory evoked potentials, peripheral nerve conduction
velocities) were used to test the children when they were afebrile and febrile.
RESULTS: ABRs, when afebrile, were abnormal with a profound delay of the IV-V and
absence of waves I-III. The ABR in one of the children, tested when febrile,
showed no ABR components. Measures of cochlear receptor function using OAEs were
normal in both febrile and afebrile states. Cochlear microphonic potentials were
present in the three children, and a summating potential was likely present in
two. When afebrile, there was a mild threshold elevation for all frequencies in
the 15-yr-old and a mild elevation of thresholds for just low frequencies in the
two siblings. Speech comprehension in quiet was normal but impaired in noise. One
of the siblings tested when febrile had a profound elevation (>80 dB) of pure
tone thresholds and speech comprehension was absent. Acoustic reflexes subserving
middle ear muscles and olivocochlear bundle were absent when febrile and when
afebrile. No other peripheral or cranial nerve abnormalities were found in any of
the children. Sensory nerve action potentials from median nerve in one of the
children showed no abnormalities on warming of the hand to 39 degrees C.
CONCLUSION: These children have an auditory neuropathy manifested by a disorder
of auditory nerve function in the presence of normal cochlear outer hair cell
functions. They develop a conduction block of the auditory nerves when their core
body temperature rises due, most likely, to a demyelinating disorder of the
auditory nerve. The auditory neuropathy in the two affected siblings is likely to
be inherited as a recessive disorder.
PMID- 9657594
TI - Psychological change over 54 months of cochlear implant use.
AB - OBJECTIVE: To determine the long-term psychological outcome of postlingually
deafened adults who received multichannel cochlear implants and to relate the
psychological outcome to audiological outcome. DESIGN: Thirty-seven recipients of
multichannel cochlear implants who participated in a prospective clinical trial
completed psychological assessments before implantation and at regularly
scheduled follow-ups through 54 mo of implant use. Standardized measures of
affect, social function, and personality were used, and scores on these measures
were correlated with asymptotic scores on several audiological measures. RESULTS:
Evidence of significant improvement on measures of loneliness, social anxiety,
and distress were obtained within a year after implantation and throughout the
duration of the follow-up period. For measures of assertiveness and marital
satisfaction, improvement was apparent only after long-term implant use. Although
favorable changes on the Minnesota Multiphasic Personality Inventory (MMPI)
Depression Scale were evidenced only in the initial follow-up period,
improvements on the MMPI Paranoia and Social Introversion Scales persisted
throughout the 54 mo follow-up. CONCLUSION: Multichannel cochlear implant use is
associated with long-term psychological benefit. Correlations between
audiological outcome and psychological outcome, however, suggested that the
relation between audiological benefit and psychological benefit is not simple.
PMID- 9657595
TI - Experiments with classroom FM amplification.
AB - OBJECTIVES: 1) To quantify the benefits of FM amplification for persons with
severe and profound hearing loss; 2) to compare a body-worn and a behind-the-ear
FM system; 3) to measure the effects of reducing FM microphone sensitivity
relative to hearing aid sensitivity. DESIGN: Recognition of phonemes in lists of
consonant-vowel-consonant words was measured in 13 teenage students with severe
and profound hearing loss. Presentation was by live voice at 10 feet from the
listeners and 12 inches from the FM microphone/transmitter. Students listened: a)
via a body-worn and a behind-the-ear system; b) with the FM
microphone/transmitter on and off; c) in noise and in quiet. Systems were
adjusted so that sinusoidal inputs of 65 dB SPL gave equal gains via the FM and
hearing aid microphones. In a follow-up study, the gain via the FM microphone was
reduced so that a sinusoidal input of 65 dB SPL into the hearing aid microphone
produced the same output as a sinusoidal input of 80 dB into the FM microphone
(as recommended in American Speech-Language-Hearing Association, 1994). RESULTS:
1) Addition of the FM microphone signal to that available from the hearing aid
microphone was equivalent, on average, to doubling the number of independent
channels of information available to the listeners. 2) FM benefit was present in
both quiet and noise but was somewhat greater in noise. 3) Contrary to
prediction, however, noise interfered with phoneme recognition even under the
aid+FM condition. 4) Differences between the body-worn and behind-the-ear systems
were small, but there was a measurable advantage for the body-worn system under
the aid+FM condition. 5) Reducing FM microphone sensitivity by 15 dB virtually
eliminated the FM benefit. 6) Forty-four percent of the variance in phoneme
recognition (averaged across listening conditions) could be explained by better
ear, three-frequency average pure-tone threshold. 7) Vowels were recognized more
easily than consonants, and initial consonants were recognized more easily than
final consonants, but the FM benefit was present for all three phonemes.
CONCLUSIONS: The findings confirm the value of FM amplification for persons with
severe and profound hearing loss, in both quiet and noise. The negative effects
of noise were not completely eliminated, however, under the aid+FM condition.
This finding can be attributed to a reduction of gain in the FM channel, when
speech input was used, because of compression limiting in the microphone
transmitter. The superiority of the body-worn system under the aid+FM condition
suggests a need for higher saturation sound pressure level in the behind-the-ear
system when used with persons having severe and profound hearing loss. The
findings do not support use of an "equal output" criterion for adjusting relative
gains via the FM and hearing aid microphones--at least for persons with very
severe and profound hearing loss operating under the conditions tested in this
study.
PMID- 9657596
TI - The effects of broadband noise masking on cortical event-related potentials to
speech sounds /ba/ and /da/.
AB - OBJECTIVE: To systematically investigate in normal-hearing listeners the effects
of decreased audibility produced by broadband noise masking on the cortical event
related potentials (ERPs) N1, N2, and P3 to the speech sounds /ba/ and /da/.
DESIGN: Ten normal-hearing adult listeners actively (button-press response)
discriminated the speech sounds /ba/ and /da/ presented in quiet (no masking) or
with broadband masking noise (BBN), using an ERP oddball paradigm. The BBN was
presented at 50, 60, and 70 dB SPL when speech sounds were presented at 65 dB ppe
SPL and at 60, 70 and, 80 dB SPL when speech sounds were presented at 80 dB ppe
SPL. RESULTS: On average, the 50, 60, 70, and 80 dB SPL BBN maskers produced
behavioral threshold elevations of 18, 25, 35, and 48 dB (average for 250 to 4000
Hz), respectively. The BBN maskers produced significant decreases (relative to
quiet condition) in ERP amplitudes and behavioral discriminability. These
decreases did not occur, however, until the noise masker intensity (in dB SPL)
was equal to or greater than the speech stimulus intensity (in dB ppe SPL), that
is, until speech to noise ratios (SNRs) were < or = 0 dB. N1 remained present
even after N2, P3, and behavioral discriminability were absent. In contrast to
amplitudes, ERP and behavioral latencies showed significant decreases at higher
(better) SNRs. Significant latency increases occurred when the noise maskers were
within 10 to 20 dB of the stimuli (i.e., SNR < or = 20 dB). The effects of
masking were greater for responses to /da/ compared with /ba/. Latency increases
occurred with less masking for N1 than for P3 or behavioral reaction time, with
N2 falling in between. CONCLUSIONS: These results indicate that decreased
audibility as a result of masking affects the various ERP peaks in a differential
manner and that latencies are more sensitive indicators of these masking effects
than are amplitudes.
PMID- 9657597
TI - Binaural masking level difference in human binaural interaction components.
AB - OBJECTIVE: The purpose of this study was to compare the effects of monaural and
binaural broadband masking noise on binaural interaction components (BICs) of the
human auditory brain stem evoked potentials (ABEPs). DESIGN: The BICs of the
human ABEPs were studied by subtracting the potentials to binaural clicks from
the algebraic sum of monaurally evoked potentials to clicks alone or to clicks
with ipsilateral monaural or binaural broadband masking noise. Alternating
polarity, 11/sec clicks were presented at 65 dB nHL, and noise was presented at
45 dB nHL. Analysis included peak-to-prestimulus baseline amplitudes and
latencies of BICs' peaks and troughs from the vertex-mastoid (A) and vertex-neck
(Z) channels. In addition, 3-channel Lissajous' trajectory (3-CLT) analysis,
estimating the single, centrally located dipole equivalent of surface activity,
was performed on data recorded from three orthogonally positioned electrode
pairs. 3-CLT measures included apex latency, amplitude, and orientation, as well
as planar segment duration, size, shape, and orientation. RESULTS: All BICs 3
CLTs included five main components (labeled BdI, BdII, BdIII, BeI, and BeII). In
general, apex latencies were longer with masking noise. However, BdII and BeI
apex latencies were shorter with binaural than with ipsilateral monaural masking
noise. Apex amplitude and planar segment size of component BeI, as well as P1
peak amplitude in BICs of the Z-channel records, were larger with binaural than
with monaural noise. No significant difference between the monaural and binaural
noise conditions was found in durations, shapes, and orientations of planar
segments of BICs 3-CLT, nor in peak latency of BICs in the A- and Z-channel
records. CONCLUSIONS: We suggest that these effects on the latency and amplitude
of BICs reflect binaural processing in the human brain stem. In particular, the
larger amplitudes and shorter latencies of P1 and BeI with binaural than with
ipsilateral monaural masking may be associated with the psychophysical effect of
binaural masking level difference.
PMID- 9657598
TI - Clinical applicability of the sweep frequency measuring apparatus for diagnosis
of middle ear diseases.
AB - OBJECTIVE: To develop a measuring apparatus that has the ability to sweep both
frequency and external auditory meatus static pressure and can display
measurement results in a three-dimensional expression. To measure the middle ear
dynamic characteristics of normal-hearing subjects and of patients with this
apparatus. DESIGN: Investigate 275 ears of 153 normal-hearing subjects and 72
ears with middle ear diseases. RESULTS: The measurement results show fairly
distinctive patterns depending on the middle ear conditions, i.e., normal,
ossicular chain separation, ossicular chain fixation, secretory otitis media,
tympanic membrane perforation, and tympanic membrane atelectasis. The evaluation
of patients with ossicular diseases revealed that the rate of correct diagnosis
of ossicular chain separation is 84% and that of ossicular chain fixation is 74%.
These diagnoses were confirmed by surgery. CONCLUSION: Displaying the measurement
results in a three-dimensional expression is helpful to make correct diagnosis in
clinical practice. It is especially easy to make a distinction between the
ossicular chain separation and ossicular chain fixation. Therefore, it is
concluded that this apparatus has a high degree of clinical applicability to the
diagnosis of these diseases.
PMID- 9657599
TI - A deterministic model for the economic evaluation of broiler production systems.
AB - A deterministic model for the economic evaluation of broiler production and the
derivation of economic values in broiler breeding was developed and tested. The
model distinguishes four production stages: multiplier breeder, hatchery,
commercial grower, and processor. The processor is included to determine
relationships for the price per kilogram of live weight and the quality of the
carcass, either on a "whole sale" or "further processed" base. Quantity of
product output for the system is fixed by a predetermined amount of kilogram
carcass of final product broilers finished by the commercial grower.
Profitability of production and cost prices per unit product for subsequent
stages can be calculated. Exogenous parameters are easily changeable in order to
calculate profitability and cost prices for different production levels or
production circumstances. Economic values can be derived considering influences
of changes in genetic merit for performance traits on profitability or cost
price, for integrated and nonintegrated production systems. By changing exogenous
parameters, the model can also be used to analyze profitability or derive
economic values for other meat-type poultry, such as turkey.
PMID- 9657600
TI - Economic values in broiler breeding.
AB - The objectives of this study were to derive economic values in broiler breeding
and to determine their relationship with production circumstances. Economic
values were derived using a deterministic economic model based on profit
equations with a fixed amount of broiler meat output of the production system.
Nonintegrated and the integrated broiler production systems were studied. The
difference between these originates from different definitions of cost components
and scaling aspects. For each stage of an nonintegrated system, the model
calculated the profit margin; for an integrated system, (total) cost prices per
unit of product at each stage were calculated. The Dutch broiler performance data
and prices were input into the model as the representative situation. For all
traits, in the nonintegrated system, economic values were derived, expressed as
Dutch guilders (Dfl) per unit of product, where the unit of product depends on
the stage of the production system and equals an egg for the multiplier breeder,
a day-old chick for the hatchery, and a marketable broiler for the commercial
grower and processor. Resulting levels of economic values were illustrated by
showing underlying cost or profit changes in the production system. For the
integrated system, economic values were expressed as Dfl x marketable broiler(-1)
x unit(-1). Economic values of traits in the integrated system were also derived
for situations where technical parameters or prices of productive factors were
changed (20% increase or decrease). A general conclusion from these sensitivity
analyses is that the economic values are sensitive to production levels, product
prices and feed prices; there are both linear and nonlinear relationships between
economic values and production circumstances.
PMID- 9657601
TI - Heterogeneity of staphylococci and other bacteria isolated from six-week-old
broiler chickens.
AB - In broiler operations, various health problems develop during the final 2 wk of
the growing period, resulting in increased mortality and condemnation losses. At
this stage, sickly birds were found to be systemically infected by various
bacteria regardless of varied clinical signs, and the purpose of this study was
to carry out thorough microbiological investigations on this problem. Thirty-one
6-wk-old broilers showing signs of illness were obtained from three farms, and
bacterial isolations were carried out from the blood, liver, and hock joint.
Bacteria were isolated from 87, 90, and 71% of the blood, liver, and hock joint
samples, respectively. Mean bacterial counts in log10 of the blood (per
milliliter) and liver (per gram) were 2.15 and 2.93, respectively. Among 132
bacterial isolates, major species were Staphylococcus (60%), Corynebacterium
(18%), Escherichia coli (5%), and Stomatococcus (4%). Among 79 Staphylococcus
isolates, 77 were coagulase-negative. Major species of staphylococci were S.
lentus (19%), S. simulans (18%), S. cohnii (13%), S. gallinarum (10%), and S.
captis (7%). In addition, six species of gram-positive and five species of gram
negative organisms were isolated. Thus, the apparent systemic infections were not
caused by predominant pathogenic bacterial species, and adequately described as
mixed infections. There were some significant relationships between isolated
bacterial species and sampling sites, suggesting that certain organisms were
abundant in the environment of a particular poultry house. These results indicate
that systemic infections in market age broilers are caused by mixed bacterial
species and suggest that they are caused by suppressed host antibacterial systems
rather than pathogenic factors of microorganisms.
PMID- 9657602
TI - Intervention decision model to prevent spiking mortality of turkeys.
AB - Based on the daily records on turkeys' mortalities for the series of flocks
placed on different farms in a relatively compact geographical area for the
period of approximately 2 yr and other relevant explanatory variables, the goal
of the research was to design a decision model to determine whether or not to use
the fluorquinolone antibiotic, sarafloxacin, to prevent spiking mortality of
turkeys. The core of the designed decision model is the forecasting model that
attempts to ex-ante predict the cumulative flock mortality for the period between
8 and 28 d of age. Forecasts were generated with the parameters of the linear
regression model where continuous values of daily mortalities served as a
dependent variable. The decision variable is a binary (yes/no) choice variable,
where "yes" means "go ahead with treatment" and "no" means "do nothing". If the
predicted cumulative mortality for the period between 8 and 28 d of age exceeds
9% of the total initial placement, the model generates a "yes" signal. If the
predicted cumulative mortality for the same period is below 9% of the total
initial placement, the model generates a "no" signal. The results indicate a
reasonable accuracy of the prediction model where the number of correct
prediction increases and the number of incorrect predictions falls very fast as
the forecasting window shortens. The intervention decision model could help
veterinarians in making decisions on whether or not to treat the suspect flocks.
PMID- 9657603
TI - Humoral immune response impairment following excess vitamin E nutrition in the
chick and turkey.
AB - The effect of high dietary intakes of vitamin E on antibody production was
investigated in chicks and turkeys. Chicks were fed four diets with 0, 10, 30,
and 150 mg/kg added vitamin E and turkeys were fed three diets with 0, 50, and
150 mg/kg added vitamin E. Antibodies produced in response to naturally occurring
Escherichia coli and to Newcastle disease virus and turkey pox vaccines were
determined. In chicks, antibody production in response to E. coli and Newcastle
disease was affected by vitamin E nutrition: significantly higher responses were
measured in chicks that received 0 and 10 mg/kg added vitamin E, whereas in
chicks receiving 30 and 150 mg/kg, antibody production was significantly lower.
In turkeys, concentrations of circulating antibodies to Newcastle disease virus
and to turkey pox were also influenced by dietary vitamin E: antibody titers to
Newcastle disease and turkey pox vaccines were highest in groups receiving 0
mg/kg added vitamin E, whereas titer in groups receiving 150 mg/kg were
significantly lower. Responses of groups receiving 50 mg/kg added vitamin E were
slightly lower than groups receiving 0 mg/kg, though not significantly so in most
cases. These results indicate that humoral immune responses are directly effected
by vitamin E, and that excessive vitamin E intake has a detrimental effect on
antibody production in chickens and turkeys.
PMID- 9657605
TI - Lymphokine-augmented activation of avian heterophils.
AB - Heterophils are important mediators of innate resistance in poultry, especially
in young birds that have not yet developed an acquired immune response. Invasion
of the intestinal mucosa by Salmonella spp. initiates the recruitment of large
numbers of heterophils to the lamina propria. Thus, the heterophilic response can
control, but not eliminate, bacterial numbers in the bird until development of
acquired immunity. Unfortunately, chicks and turkey poults are highly susceptible
to Salmonella infections during the first 4 d posthatch due to the functional
immaturity of both the innate and acquired immune systems. We have previously
shown that the administration of Salmonella enteritidis (SE)-immune lymphokines
(ILK) into either 18-d-old developing embryos or day-of-hatch chicks and poults
conferred increased resistance to SE organ invasion. In this review, we present
evidence that the protection induced by ILK is mediated by vigorous recruitment
and activation of heterophils. These activated heterophils migrate rapidly to the
site of bacterial invasion where they phagocytize and kill the SE. Specifically,
in vitro studies demonstrate an enhancement of functional activities of the
heterophils including chemotaxis, adherence, phagocytosis, and bacterial killing.
In addition, during the activation process, membrane expression of adhesion
molecules rapidly changes from L-selectins to beta2 integrins (CB11b/CD18) on the
cells that become activated. These results further demonstrate the validity of
preventive activation in poultry to induce the migration of large numbers of
activated phagocytic cells to the site of infection by a pathogenic organism.
Importantly, this immunopotentiation of the inflammatory response by ILK, as
described here, induces the functional maturation of heterophils during the first
4 d posthatch.
PMID- 9657606
TI - Avian heterophils in inflammation and disease resistance.
AB - Heterophils are the predominate granulated leukocyte in the acute inflammatory
response in gallinaceous birds. Heterophils are highly phagocytic and are capable
of a broad spectrum of antimicrobial activity. They accumulate in inflamed
tissue, causing tissue damage and forming heterophil granulomas that are
morphologically similar to inflammatory lesions in reptiles. The avian heterophil
lacks myeloperoxidase and depends primarily on nonoxidative mechanisms for
antimicrobial activity. The beta-defensins found in heterophil granules can kill
a wide variety of bacterial pathogens and are a major component of the heterophil
antimicrobial arsenal. Heterophils form the first line of cellular defense
against invading microbial pathogens in the lungs and air sacs where resident
macrophages are lacking.
PMID- 9657607
TI - Role of macrophages in avian health and disease.
PMID- 9657608
TI - Avian macrophages: regulators of local and systemic immune responses.
AB - Macrophages are key regulatory cells of the immune system involved in initiating
and directing the innate and specific immune responses, the systemic acute phase
response, tissue repair, and tissue remodeling. In the early stages of a
challenge from invading microorganisms or from tissue injury, macrophages defend
local and systemic homeostasis by initiating a complex series of cellular,
biochemical, and behavioral events. These pathophysiological adjustments are
mediated by an extensive variety of communication molecules, including:
cytokines, cytokine inhibitors, endocrine hormones, eicosanoids,
neurotransmitters, and reactive oxygen intermediates. The cytokines produced by
macrophages (monokines) are not well characterized relative to their mammalian
counterparts, but a variety of chemokine, pro-inflammatory, and colony
stimulating factor activities have been described. Although the sequence
homology, and thus species cross-reactivity, between avian and mammalian
cytokines is typically low, the functional characteristics appear to be generally
similar. The pro-inflammatory cytokines are important initiators and regulators
of the local immune response. They are also released in sufficient quantities
during some infections to coordinate a systemic acute phase response that impacts
the growth, reproduction, and well-being of poultry. An understanding of the
mechanisms and molecules used by macrophages to regulate immune and inflammatory
responses may permit the development of products, diets, or husbandry techniques
to modulate immunity for the enhancement of the productivity of poultry.
PMID- 9657609
TI - Avian macrophage metabolism.
AB - This review considers the role of avian macrophages as a source of immune
effector and immunoregulatory metabolites. Although considerable attention has
been given to the importance of leukocytic cytokines, particularly the monokines
such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha
(TNF-alpha), and transforming growth factor-beta (TGF-beta), metabolites produced
by macrophages appear to be of equal importance in determining the progression of
immune responses. The three metabolite categories that have received the greatest
attention are the reactive oxygen species (ROS), the reactive nitrogen
intermediates (RNI), and the eicosanoids. Additionally, the xenobiotic
metabolites produced via cytochrome P450 activity mediate some immune
environmental interactions. Each of these four metabolite categories is subject
to different requirements for metabolite production, and each has distinct
effector functions. An understanding of macrophage metabolite regulation could
allow improvements in avian health management and production via the effective
control of metabolite production. The present review considers prior and recent
information on the production of the metabolites by avian macrophages.
Additionally, the potential ramifications of metabolite production and regulation
are discussed.
PMID- 9657610
TI - Threonine requirements of laying hens.
AB - In order to determine the Thr requirement of laying hens, two experiments were
conducted using laying performance and plasma Thr concentration as parameters. At
29 and 39 wk of age, 100 and 600 laying hens in Experiments 1 and 2,
respectively, with average BW and high egg production rate, were randomized,
housed in individual cages, and given free access to water and experimental diets
with five graded levels of Thr: 0.31, 0.39, 0.46, 0.54, and 0.61% for 21 d in
Experiment 1 and diets with 0.31, 0.36, 0.41, 0.46 and 0.51% Thr for 58 d in
Experiment 2. On the last day of the experiment, blood samples were taken for
determination of plasma amino acid concentration. Feed intake and daily egg mass
increased and then decreased linearly as dietary Thr increased. Plasma Thr
increased slowly, then sharply with increasing dietary Thr levels. Using the
broken-line model, the Thr requirements were estimated to be 0.425, 0.428, and
0.430% or 453, 456, and 458 mg/hen per d in Experiment 1 and 0.395, 0.404, and
0.400%, or 457, 467, and 462 mg/hen per d, in Experiment 2, for egg mass, feed
efficiency, and plasma Thr concentration, respectively. These results indicate
that the Thr requirements expressed as milligrams per hen per day as determined
by plasma Thr concentration agree with those of laying performance.
PMID- 9657611
TI - Bioavailability of the digestible lysine and total sulfur amino acids in meat and
bone meals varying in protein quality.
AB - Experiments were conducted to determine whether the digestible Lys, Met, and TSAA
in a high and low quality meat and bone meal (MBM) were totally bioavailable for
protein synthesis in chicks. True digestibility of amino acids (AA) in the two
MBM was determined by the precision-fed cecectomized rooster assay.
Bioavailability of the digestible AA was then assessed in three slope-ratio chick
growth assays using Lys-, Met-, or TSAA-deficient crystalline AA basal diets that
were supplemented with varying levels of the test AA, high or low quality MBM, or
AA mixtures simulating the mean digestible AA composition of the high and low
quality MBM. Response parameters were weight gain, feed efficiency, body N gain,
and body Lys gain in the Lys assay and weight gain and feed efficiency in the Met
and TSAA assays. Bioavailability values for the digestible Lys, Met, and TSAA in
the MBM and AA mixtures simulating MBM varied depending on response parameter,
with values based on feed efficiency generally being highest. No consistent
differences in bioavailability of the digestible AA were observed between the two
MBM when all AA were considered; however, the bioavailability of the digestible
Lys in the low quality MBM was lower than that in the high quality MBM for two of
four performance criteria. When considering all response parameters and the AA
mixture results, bioavailability of the digestible Lys and Met in the two MBM was
generally 90% or greater, whereas bioavailability of the digestible TSAA was only
80% or less. The results of this study indicated that essentially all of the
digestible Lys and Met in MBM were bioavailable for protein synthesis and
metabolism but suggested that a significant amount of the TSAA, particularly Cys,
was not bioavailable.
PMID- 9657612
TI - Dietary formulation with meat and bone meal on a total versus a digestible or
bioavailable amino acid basis.
AB - The digestibility and bioavailability of amino acids (AA) in meat and bone meals
(MBM) may vary greatly due to different processing conditions. In the present
study, two experiments were conducted to evaluate formulation of diets containing
high or low quality MBM on a total AA basis vs a digestible or bioavailable AA
basis compared to a corn-soybean meal control diet. Lysine, methionine, and
cystine digestibilities (precision-fed cecectomized rooster assay) were 92, 91,
and 71%, respectively, for high quality MBM and were 71, 83, and 31%,
respectively, for the low quality MBM. Bioavailability values (slope-ratio chick
growth assay) for TSAA in the two MBM were approximately 15 percentage units
lower than the digestibility values. Male crossbred chicks were fed a 20% CP corn
SBM diet or corn-SBM diets containing 10 or 20% high or low quality MBM that were
formulated to be equal in total, digestible, or bioavailable AA to the corn-SBM
diet. All diets contained 3,200 kcal of TMEn/kg, 1.4% Ca, and 0.7% nonphytate P
and were fed to chicks from 8 to 22 d posthatching. Growth performance of chicks
fed 10 or 20% high or low quality MBM on a total AA basis was lower (P < 0.05)
than that of chicks fed the corn-SBM diet. Growth of chicks fed 10% low quality
MBM or 10 or 20% high quality MBM on a digestible or bioavailable basis was
equivalent to that of chicks fed the corn-SBM diet; however, dietary inclusion of
20% low quality MBM depressed growth (P < 0.05) even on a digestible or
bioavailable AA basis. Further supplementation of the latter diet with additional
AA yielded growth that was similar to the corn-SBM control diet. The results
indicated that formulation of diets containing MBM on a digestible or
bioavailable AA basis is superior to formulation on a total AA basis. However,
feeding high levels of a low quality MBM may require additional AA
supplementation to obtain maximum chick growth.
PMID- 9657613
TI - Availability of amino acids in high-oil corn.
AB - True digestibility of amino acids, bioavailability of Lys, and TMEn in three
types of high-oil corn (HOC) and one conventional corn (CC) were determined. The
CC, HOC1, HOC2, and HOC3 contained 4.3, 5.9, 6.6, and 9.5% ether extract,
respectively, on a DM basis. True digestibility of amino acids was determined
using the precision-fed cecectomized rooster assay in which each corn sample was
tube-fed (30 g) to nine roosters and excreta were collected for 48 h. True
digestibility of most amino acids in HOC2 and HOC3 were significantly higher (P <
or = 0.05) than those in CC and HOC1. Mean digestibility of 15 amino acids in
HOC2 and HOC3 was 91% compared to 80% for CC and HOC1. The TMEn values
(kilocalories per gram DM) of CC, HOC1, HOC2, and HOC3 were 3.883, 4.024, 4.038,
and 4.140, respectively. Lysine bioavailability was assessed using a slope-ratio
chick growth assay in which a Lys-deficient crystalline amino acid diet was
supplemented with 0, 0.1, or 0.2% L-Lys from L-Lys x HC1 to provide a standard
curve. Six additional dietary treatments consisted of supplementing the basal
diet with 28 or 56% of CC, HOC2, or HOC3. The nine diets were fed to four
replicate groups of six chicks from 8 to 18 d posthatching. Lysine
bioavailability was calculated using multiple regression slope-ratio methodology
where Y was weight gain and X was intake of Lys from the L-Lys x HC1 or a corn.
Supplementation of the basal diet with L-Lys x HC1, CC, HOC2, or HOC3 yielded
linear (P < or = 0.001) growth responses. Bioavailability values (percentage) for
the Lys in CC, HOC2, and HOC3 relative to the Lys in L-Lys x HC1 were 65 +/- 10,
72 +/- 10, and 91 +/- 8, respectively. The results of this study indicated that
digestibility of amino acids and bioavailability of Lys in HOC are equal to or
greater than those in CC.
PMID- 9657614
TI - An evaluation of threonine requirements of young turkeys.
AB - Two experiments were conducted to evaluate the Thr requirements of male Large
White turkeys from 3 to 6 and 6 to 9 wk of age. One group of turkeys was fed to 3
wk using nutritionally adequate diets and fed test diets from 3 to 6 wk; another
group of turkeys was fed to 6 wk using nutritionally adequate diets and fed test
diets from 6 to 9 wk. Test diets were composed of peanut meal, soybean meal,
corn, and grain sorghum as intact protein sources and were supplemented with
amino acids. Peak performance of turkeys fed the test diets was equivalent to
that of turkeys fed conventional corn-soybean meal diets formulated to meet NRC
(1994) standards. Estimates of Thr requirements for weight gain were 0.92 and
0.86% for 3 to 6 and 6 to 9 wk, respectively. For feed conversion, estimates of
Thr requirements were 0.87% and 0.84% for 3 to 6 and 6 to 9 wk, respectively. The
results of the two experiments reported herein would suggest that the Thr
requirements suggested by NRC (1994) for turkeys up to 9 wk of age are safe
estimates; they may slightly overestimate the requirements but not by a large
margin.
PMID- 9657615
TI - Effects of dietary taurine on egg weight.
AB - Two experiments were conducted to determine whether taurine supplementation to
laying hens would influence laying performance. In Experiment 1, a total of 120
White Leghorn hens were fed diets supplemented with 0, 0.25, or 0.5% taurine for
5 wk. Egg weight was reduced significantly by supplementing 0.25 and 0.5%
taurine; however, taurine did not affect other laying performance variables. In
Experiment 2, a total of 240 White Leghorn hens were fed diets supplemented with
0 or 0.5% taurine and 0 or 0.1% methionine for 7 wk. Egg weight was decreased due
to supplementing taurine in the diets; however, dietary methionine did not affect
egg weight, and there was no interaction between dietary taurine and methionine.
These results suggest that dietary taurine has the potential to decrease egg
weight without affecting egg production, feed conversion, or body weight.
PMID- 9657616
TI - Locus-specific diagnostic tests for endogenous avian leukosis-type viral loci in
chickens.
AB - The genome of the chicken, Gallus gallus, contains endogenous proviral elements
(ALVE elements or ev genes) that display a high degree of similarity to the Avian
Leukosis class of retroviruses. The ALVE proviruses are known to modulate
physiological processes of the host birds. Different ALVE elements retain
variable portions of the complete, prototype viral genome, and each provirus
resides in its own specific location within the host genome. Thus, each ALVE
element has its own particular potential to modulate host physiology depending on
the nature of its integration site, the completeness of the proviral genome, and
the level of expression of the locus. It is important, therefore, to be able to
establish the ALVE element profiles of chickens quickly and accurately, both in
the laboratory and in a commercial setting. The current method of choice for
simple, quick, and accurate typing is the polymerase chain reaction (PCR). This
paper reviews the present status of PCR typing of ALVE proviruses and lists the
assay protocols for 19 different elements. In addition, it compares the insertion
sites of these elements in an effort to identify common motifs at ALVE
integration sites.
PMID- 9657617
TI - Characterization of turkey spermiophages with regard to traits common to
macrophages.
AB - Turkey peritoneal exudate cells (PEC) and spermiophages (SMO) were assayed for
characteristics of macrophages. The PEC elicited by i.p. injection of 3% Sephadex
and SMO isolated from semen using Percoll were cultured in Dulbecco's Modified
Eagle Medium supplemented with 20% bovine calf serum (DMEM-20) for 24 h at 41 C
in 5% CO2 to provide adherent cells for assays. Most PEC and SMO showed esterase
activity (99.3 +/- 0.6 and 98.8 +/- 0.9%, respectively), and exhibited
nonspecific phagocytosis of carbon (89.5 +/- 3.6 and 95.3 +/- 0.6%,
respectively), zymosan (26.5 +/- 7.6 and 24.3 +/- 2.5%, respectively), bacteria
(11.3 +/- 0.8 and 9.3 +/- 0.3%, respectively), and opsonized and nonopsonized
SRBC. Maximum uptake of SRBC was seen by 2 h for PEC but not until 4 h for SMO.
At time of maximum uptake, SRBC were noted in 35 to 40% of PEC but only in 15 to
20% of SMO. Turkey IgG-FITC bound to both PEC and SMO, but goat anti-turkey IgG
FITC bound only to SMO. Increased nitrite was found in turkey semen after 24 h
storage, with highest levels in samples in which SMO were added. Nitrite
production was demonstrated using adhered PEC, but SMO could not be tested due to
low cell numbers. This research clearly identifies SMO as having macrophage-like
activities. Accordingly, these cells may possess the ability to process and
present antigen via histocompatibility receptors. Such activity could lead to
immune directed responses, including antibody production or activation of
cytotoxic T-lymphocytes.
PMID- 9657618
TI - Echocardiographic evaluation of cardiac structure and function in broiler and
Leghorn chickens.
AB - This study was conducted to validate echocardiography in chickens, and to compare
cardiac structure and function between broiler and Leghorn chickens. Diameters of
the right and left ventricles, and thicknesses of the left ventricular free wall
and the interventricular septum were measured echocardiographically in 5- and 7
wk-old chickens from both lines. Images were obtained from minimally restrained,
standing birds using a 7.5 MHz probe placed in a parasternal position. End
systolic and end-diastolic echocardiographic measurements were compared with post
mortem measurements of the same variables. Comparisons resulted in correlation
coefficients greater than 0.70 between in vivo (echocardiographic) and post
mortem measurements of the same variables, with post-mortem measurements more
closely resembling end-diastolic echocardiographic measurements. After being
normalized to body weight, post-mortem myocardial thicknesses, aortic and left
ventricular diameters, heart weight at 5 wk of age, and left ventricular weight
at 7 wk of age were smaller in broiler than in Leghorn chickens.
Echocardiographic parameters, including ventricular wall thicknesses, ventricular
diameters, and left ventricular fractional shortening, were also smaller in the
broiler chicken. Right ventricular fractional shortening did not differ between
the chicken lines. These results indicate that echocardiography is a useful
noninvasive technique for in vivo evaluation of cardiac structure and function in
the chicken, and that broiler chickens have a relatively smaller structural and
functional heart than Leghorn chickens.
PMID- 9657619
TI - Effects of varying aeration treatment on fertilizing capacity of semen diluted
with perfluorochemical emulsion and stored for twenty-four hours.
AB - The effects of perfluorochemical (PFC) oxygen carriers in turkey semen diluents
on fertility and hatchability was measured for a 10-wk period. Semen was diluted
(1:1) with Beltsville Poultry Semen Extender (BPSE) or BPSE:FC-75, an emulsified
mixture of BPSE and perfluorobutyltetrahydrofuran (technical grade) (FC-75) and
stored for 24 h at 5 C with agitation (150 rpm) and aeration with either air,
nitrogen (100%), or oxygen (100%). Sperm concentration and percentage of dead
sperm were determined prior to and after storage. Sperm concentration (8.35 to
9.21 x 10(9) per milliliter) was not significantly affected by the type of
diluent or aeration gas, and only stored semen diluted with BPSE: FC-75 and
aerated with nitrogen had increased percentage of dead sperm. Diluent type did
not affect the percentage of fertilized eggs; however, fertility and hatchability
for both diluent treatments with nitrogen aeration was significantly lower (P <
or = 0.05) than for the semen treatments with air or oxygen aeration.
Hatchability for semen diluted with BPSE:FC-75 and aerated with oxygen (63.7%)
was significantly higher (P < or = 0.05) than that for BPSE-diluted semen aerated
with oxygen (43.2%). Although use of oxygen carrying fluorocarbon emulsified with
BPSE did not further improve fertility when the semen was stored for 24 h while
oxygenated and mechanically agitated, a beneficial effect was noted for
hatchability. The fact that nitrogen severely depressed fertility confirms that
the beneficial effects of agitation are due to oxygenation of the spermatozoa.
Therefore, further studies of oxygen carriers in semen are warranted.
PMID- 9657620
TI - Dietary methionine intake effects on egg component yield, composition,
functionality, and texture profile analysis.
AB - The influence of supplemental Met levels ranging from 413 to 556 mg per hen per d
(mg/HD) on liquid egg component yield, composition, and functionality was
examined in mature layers (29 wk of age). Egg weight, component yield, solids,
and CP content of albumen and yolk were determined. Texture profile analysis,
feed ingredient functionality testing, and PAGE were conducted to determine
whether increased egg total solids and CP content resulted in altered egg
component functionality or electrophoretic protein banding pattern. Albumen
component yield increased significantly on a mass basis at 507 and 556 mg/HD Met
compared to 413 mg/HD Met. Yolk mass yield was significantly increased at 556
mg/HD Met compared to 413 mg/HD Met. Consumption above 413 mg/HD Met resulted in
significantly increased albumen total solids and protein. Yolk solids were not
significantly different; however, yolk CP was significantly increased at 507 and
556 mg/HD Met compared to 413 mg/HD Met. Albumen and yolk functionality at 413
and 507 g/HD Met were not significantly different in relation to cake volume or
height. Emulsion separation at 120 min was significantly increased for 556 mg/HD
Met compared to 413 and 507 g/HD Met. There were no significant differences in
hardness or springiness of albumen and yolk gel plugs and electrophoretic protein
banding patterns. Increased understanding of the influence of Met on liquid egg
yield and composition may provide the egg producer with an effective and
advantageous management technique for shell egg production specifically managed
to maximize liquid egg product.
PMID- 9657621
TI - Time course of complete normalization of left ventricular hypertrophy during long
term antihypertensive therapy with angiotensin converting enzyme inhibitors.
AB - Metaanalyses have indicated that ACE inhibitors are more effective than other
first-line therapies in reducing left ventricular hypertrophy (LVH). The average
treatment period, however, was only approximately 6 months. The aim of the
present study, therefore, was to clarify the time course and degree of reversal,
and primarily to find out in how many patients a complete normalization of LVH
can be achieved. Secondly, we sought to determine whether atrial enlargement can
be reduced. Previously untreated hypertensive patients (mean age 46.3 +/- 9
years, eight women, 15 men) with echocardiographically confirmed LVH (left
ventricular mass index ([LVMI] > 125 g/m2 for men; > 110 g/m2 for women) were
prospectively treated over a 3-year treatment period with quinapril. Nine
patients received 10 mg quinapril, 12 received 20 mg of quinapril daily, and five
patients additionally received 25 mg hydrochlorothiazide. The time course of
changes in LVMI, relative wall thickness, left atrial size, fractional
shortening, and diastolic function was evaluated and ambulatory blood pressure
monitoring (ABPM) and an exercise test were performed every 6 months. After a
mean treatment period of only 7.5 months, there was a significant (P < .001),
17.5% decrease in LVMI with a further continuous and significant (P < .001)
decrease of 38.6% after 38.3 +/- 3 months of therapy. In 90.5% of the patients a
complete reversal of LVH was achieved. Fractional shortening increased
significantly, the maximum being 14.6% after 38.3 +/- 3 months. The peak
early/atrial velocity (E/A) ratio increased significantly (P < .01) after just
7.5 +/- 3.1 months with no further changes during follow-up. There seemed to be a
parallel change with the decrease in left atrial dimension, where the most
important decrease occurred after only 7.5 +/- 3.1 months (P < .01), with a
further continuous reduction. Our study clearly shows that maximum reversal of
LVH is a time-consuming process and that an essential goal of antihypertensive
therapy should be not only a reduction in LVH but also a normalization in LV
mass, left atrial size, and in diastolic dysfunction.
PMID- 9657622
TI - Comparison of spirapril, isradipine, or combination in hypertensive patients with
left ventricular hypertrophy: effects on LVH regression and arrhythmogenic
propensity.
AB - This study was designed to evaluate in 45 hypertensive patients with left
ventricular hypertrophy (LVH) the effects of a 6-month course with one of three
different antihypertensive regimens (the calcium channel blocker isradipine, the
angiotensin converting enzyme inhibitor spirapril in monotherapy, or a
combination of the two drugs, n = 15 per group) on blood pressure, LVH
regression, and various functional correlates of LVH. All three treatment
modalities decreased significantly LV mass index by an average of 10%, although
the combination had the greatest blood pressure-lowering effect and spirapril had
the least, as assessed by office resting pressures, ambulatory monitoring, and
isometric grip testing. There was no correlation between magnitude of blood
pressure lowering and degree of LVH regression. The effects of treatment on
pressor hormone profiles differed among groups, as spirapril tended to suppress
angiotensin II and norepinephrine, whereas isradipine had opposite effects.
Exercise tolerance was prolonged by all three regimens, but significantly more by
the combination. All three regimens decreased significantly the double product by
10% to 15%. Indices of electrophysiologic stability calculated from analysis of
ambulatory electrocardiogram exhibited significant improvement in several
parameters such as QRS duration, presence of late potentials, and measures of
heart rate variability, resulting in fewer episodes of simple or complex
ventricular arrhythmia. We conclude that all three regimens produce significant
LVH regression associated with improved functional capacity and electrical
stability. These results reflect the sum of the differential hemodynamic and
hormonal effects exerted by each treatment modality.
PMID- 9657623
TI - Vagal cardiac activity in essential hypertension: the effects of metoprolol and
ramipril.
AB - Cardiovascular parasympathetic activity is attenuated in essential hypertension.
Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors
have been reported to increase vagal modulation of heart rate and baroreflex
sensitivity, but the relations between the antihypertensive and vagal cardiac
effects of these drugs have remained unclear in essential hypertension. In the
present study we evaluated the effects of a 4-week crossover monotherapy with
metoprolol and ramipril on spectrum analysis indices of heart rate variability in
the supine rest and head-up tilted positions, baroreflex sensitivity
(phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly
untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment
values, both drugs decreased BP similarly and significantly. However, the drugs
showed different effects on cardiac vagal activity: metoprolol increased
significantly mean R-R interval, R-R interval total, and high-frequency
variability at supine rest and baroreflex sensitivity, but ramipril did not
significantly affect these variables. The metoprolol-induced decrease in
ambulatory BP correlated with the prolongation of the R-R interval and the
increase of high-frequency variability at supine rest. The present data show that
4-week treatment with metoprolol increases tonic and reflex vagal cardiac
activity, whereas ramipril does not affect vagal cardiac control in essential
hypertension. Increase in vagal activity may contribute to the BP-lowering effect
of metoprolol in hypertensive patients.
PMID- 9657624
TI - Acute cardiovascular effect of 1,25-dihydroxycholecalciferol in essential
hypertension.
AB - A role for vitamin D in the pathophysiology of essential hypertension has
frequently been suggested, but acute direct effects on blood pressure, cardiac
output, renal hemodynamics, or hormones have not previously been demonstrated.
The rapid effects of 1,25-dihydroxycholecalciferol (1,25-D) were assessed over
120 min after a bolus injection (0.02 microg/kg body weight) in eight men with
essential hypertension and in nine healthy men. A placebo group of 10 healthy men
was also included. Ionized calcium was monitored closely during the study, and
was kept constant with a clamping technique. In the hypertensive patients, a
transient increase in blood pressure and a reciprocal fall in cardiac output
measured by a CO2 rebreathing technique (-15%, P < .05) were observed after 1,25
D injection. In the control group, both blood pressure and cardiac output
remained unchanged. The glomerular filtration rate, effective renal plasma flow,
and urinary sodium and water excretions were unchanged in both groups. Plasma
levels of atrial natriuretic peptide at baseline were higher in the hypertensive
patients than in the control subjects (P < .02); plasma levels of renin,
aldosterone, norepinephrine, endothelin, and parathyroid hormone(1-84) were
similar in the two groups. None of these hormones was affected during the
observation time after the injection of 1,25-D. In conclusion, acute
administration of 1,25-D caused a fast and likely nongenomic-mediated decrease in
cardiac output in patients with essential hypertension, which together with a
transient BP increase implies a 1,25-D-induced increase in total peripheral
resistance. These data suggest an enhanced cardiovascular responsiveness to 1,25
D in hypertensive compared to healthy normotensive subjects.
PMID- 9657625
TI - Endogenous digoxin-like immunoactivity in subjects with diabetes mellitus and
hypertension.
AB - The serum concentrations of digoxin-like immunoactivity (DLIA) were measured in
99 patients: 20 healthy volunteers (HV), 15 patients with insulin-dependent
diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes
mellitus without hypertension taking oral hypoglycemic (OHA) agents (NIDDM/-HT),
11 patients with NIDDM without hypertension taking insulin (NIDDM/-HT+INS), 12
NIDDM patients with hypertension taking OHA (NIDDM/+HT), nine NIDDM patients with
hypertension taking insulin (NIDDM/+HT/+INS), 10 patients with essential
hypertension with normal insulin levels (HT/-HI), and in eight patients with
essential hypertension with hyperinsulinemia (HT/+HI). The numbers (%) of
subjects with DLIA levels above the detection limit of the assay used (> 0.1
nmol/L) were, in the NIDDM/-HT group, 12/14 (85.7%) and in the NIDDM/+HT group,
9/12 (75%), significantly higher (P < .05) than in the HV (7/20; 35%), IDDM
(3/15; 20%), and HT/-HI groups (2/10; 20%). The number and percentage of subjects
with DLIA levels above the detection limit in the HT/+HI group was six of eight
(75%), significantly (P < .05) higher than in the IDDM and HT/-HI groups, and
tended to be higher than in the HV group (P < .055). Means and SD of serum DLIA
levels (nmol/L) in the NIDDM/-EH (0.18/0.09) and NIDDM/+EH (0.19/0.15) groups
were significantly higher (P < .05) than in the HV (0.09/0.07), IDDM (0.05/0.05),
and EH/-HI (0.06/0.06) groups. DLIA levels in the HT/+HI group (0.15/0.12) were
significantly higher (P < .05) than in the IDDM and HT/-HI groups. The percentage
of DLIA levels above the detection limit, as well as the mean and SD of DLIA in
the NIDDM group taking OHA, did not differ from those in subjects taking insulin.
In all subjects studied (n = 99), DLIA correlated with C-peptide (r = 0.30; P <
.01) and glomerular filtration (GF) (r = -0.21; P < .05). After exclusion of
insulin-treated patients, DLIA correlated significantly with plasma glucose (PG;
r = 0.25; P < .05), immunoreactive insulin (IRI; r = 0.41; P < .001), C-peptide
(r = 0.27; P < .05), and GF (r = -0.26; P < .05) (n = 64). Correlation of DLIA
with IRI (r = 0.33; P < .05; n = 38) also persisted after exclusion of patients
taking insulin and those with DLIA levels below the detection limit. Similarly,
DLIA also correlated with C-peptide (r = 0.64; P < .05) and IRI (r = 0.70; P <
.05) in the subgroup of 10 patients with the highest levels of DLIA (> 0.25
nmol/L). None of the sera (n = 15) with different DLIA concentrations (0.0-0.38
nmol/L) exhibited K-pNPPase (Na+-K+-ATPase) inhibitory activity. In conclusion,
this work demonstrated elevated serum DLIA in NIDDM and HT/+HI patients, and its
correlation with IRI and GF. However, due to the fact that the chemical nature
and biologic properties of DLIA are still a matter of debate, it is too early to
speculate whether the elevation of DLIA is just a secondary result associated
with HI and reduced GF, or whether it also has pathophysiologic consequences.
Nevertheless, in both cases the elevated concentrations of substances with DLIA
and their interference with antidigoxin antibodies may affect therapeutic
monitoring of digitalization in NIDDM and HT/+HI patients. Also, the elevated
DLIA could subclassify these patients. The significance of such
subclassifications (pathophysiologic, therapeutic, or prognostic), however, will
need further investigation.
PMID- 9657626
TI - Acute effects of cigarette smoking on platelet function and plasma catecholamines
in hypertensive and normotensive men.
AB - In this randomized controlled crossover study essential hypertensive men (n = 13)
and matched normotensive controls (n = 18) were examined before and during
cigarette and sham smoking to assess the acute effects of smoking on platelets
and plasma catecholamines. Platelet activity in vivo was determined by
measurements of the released alpha-granule constituent beta-thromboglobulin (beta
TG) in plasma and in urine. Urinary high molecular weight beta-TG and venous
plasma epinephrine increased significantly during smoking in the hypertensive
group, but not among the normotensive men. Thus, cigarette smoking induces a mild
platelet release reaction and also elicits a significantly higher epinephrine
response in hypertensive men compared to normotensive controls.
PMID- 9657627
TI - Effects of an ACE inhibitor and a calcium channel blocker on cardiovascular
autonomic nervous system and carotid distensibility in patients with mild to
moderate hypertension.
AB - We investigated the relationship between cardiovascular autonomic nervous system
function and carotid arterial distensibility during treatment with an angiotensin
converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine)
for hypertension. In 37 patients with hypertension, autonomic function was
assessed by heart rate variability and baroreceptor sensitivity using
phenylephrine injection. Left ventricular mass index and carotid arterial
distensibility were assessed by ultrasound examinations. Before the medication,
both baroreceptor sensitivity and heart rate variability correlated with carotid
arterial distensibility, but not with left ventricular mass index by multiple
regression analysis. Subsequently, patients were randomly allocated into two
groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the
study, the change in baroreceptor sensitivity correlated with change in carotid
arterial distensibility (r = 0.41, P < .05), but not with change in left
ventricular mass index. Although derapril and manidipine decreased blood pressure
and left ventricular mass index to the same extent, the former improved heart
rate variability, baroreceptor sensitivity (5.0 +/- 1.9 --> 5.6 +/- 2.0 msec/mm
Hg), and carotid arterial distensibility (2.1 +/- 0.8 --> 2.5 +/- 1.0 %kPa), but
the latter did not improve them at all. Thus, impairment of the autonomic balance
was related to the impairment of carotid arterial distensibility in hypertension;
derapril, but not manidipine, significantly improved these abnormalities.
PMID- 9657628
TI - Effect of amlodipine versus felodipine extended release on 24-hour ambulatory
blood pressure in hypertension.
AB - Amlodipine and felodipine are calcium antagonists of the dihydropyridine type.
The elimination half-life of amlodipine is longer than that of felodipine. To
study whether the different elimination rates of the drugs were reflected in
different duration of blood pressure (BP) control, we compared amlodipine and
felodipine extended release (ER) by both conventional clinic BP 24 h after drug
intake and 24 h ambulatory BP monitoring (ABPM), with special reference to
nighttime and morning blood pressure. Two hundred and sixteen patients with
primary hypertension (supine diastolic BP, 95 to 115 mm Hg) were randomized to
receive amlodipine or felodipine ER in a multicenter study. The starting dose of
both drugs was 5 mg. If the target clinic diastolic BP (90 mm Hg) had not been
achieved after 4 weeks the dose was increased to 10 mg. Twenty-four-hour ABPM was
performed with the subjects taking placebo medication before randomization and
after 4 and 8 weeks undergoing active treatment. Significantly more patients
responded after 4 weeks of treatment with amlodipine (50%) as compared with
felodipine (33%) (P = .013). ABPM during daytime (07:00 to 23:00) was similar
during both treatments, but nighttime systolic (P = .026) and diastolic (P =
.019) BP was more effectively reduced by amlodipine than by felodipine. After 8
weeks 82% achieved the target pressure with amlodipine and 69% with felodipine (P
= .036 for the difference). Amlodipine seems to be more effective than felodipine
when the drugs are compared in the same dose, with regard to the effect on clinic
BP 24 h after dosing and to ambulatory BP during the night. The longer
elimination half-life of amlodipine as compared to felodipine is the probable
reason for this finding.
PMID- 9657629
TI - Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy
induced in rats by prolonged inhibition of nitric oxide synthesis.
AB - We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor
imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate,
to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with
hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats
were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME)
500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50
mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine
samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and
histologically examined the kidney and heart. L-NAME markedly reduced the levels
of NO metabolites in serum and urine while increasing the tail-cuff blood
pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g
in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/-
1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were
documented histologically. The plasma renin activity was significantly higher in
rats treated with L-NAME than in the control rats. The concomitant administration
of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure,
the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the
histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced
effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in
rats produced nephrosclerosis and LVH that were effectively prevented by giving
imidapril at a dose lower than that of amlodipine. We conclude that ACE
inhibitors can prevent nephrosclerosis and LVH even in the presence of a
reduction in NO production, implying that in rats the inhibition of the renin
angiotensin system is more effective than the blockade of calcium channels in
preventing hypertensive tissue injury.
PMID- 9657630
TI - Role of nitric oxide in cocaine-induced acute hypertension.
AB - Cocaine causes acute hypertension by blocking catecholamine reuptake. There is
evidence that it also impairs the peripheral endothelial nitric oxide system,
which is normally vasodilatory. We further explored the role of nitric oxide in
cocaine-induced vasoconstriction in anesthetized rats, and in vitro by using
isolated carotid artery segments. Cocaine administered intravenously in rats
increased mean arterial pressure by 30 to 40 mm Hg within 1 min. This effect was
dose dependent and the maximum effect was observed at a dose of 1.25 mg/kg. The
prototype catecholamine norepinephrine induced a similar increase in blood
pressure. When rats were pretreated with NG-monomethyl-L-arginine (L-NMMA, a
blocker of nitric oxide) and challenged with cocaine, the increase in blood
pressure was blocked by 80%, whereas pretreatment with L-NMMA did not block
norepinephrine-induced vasoconstriction. Both cocaine and norepinephrine also
induced an immediate vasoconstriction in isolated carotid artery preparations.
The in vitro vasoconstriction induced by cocaine was blocked by pretreatment with
L-NMMA, whereas L-NMMA did not block the norepinephrine-induced vasoconstriction
in vitro. Furthermore, carotid artery stripped of endothelium responded to
norepinephrine but failed to respond to L-NMMA or cocaine. S-nitroso-N-acetyl-D,L
penicillamine (SNAP)-a precursor of nitric oxide- stimulated nitric oxide
production in control coronary artery fragments. When these fragments were
incubated with cocaine there was a 20% reduction in the production of nitrite
oxide. These results suggest that cocaine exerts its peripheral vasoconstriction
at least in part by inhibiting local vasodilator nitric oxide.
PMID- 9657631
TI - Tissue-specific regulation of growth factors and clusterin by angiotensin II.
AB - Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic
responses of the heart and kidney to systemic hypertension. To determine whether
these actions of ANG II are related to tissue-specific stimulation of growth
factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low
dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or
low-dose ANG II were normotensive with normal plasma aldosterone concentration,
whereas rats receiving high-dose ANG II were hypertensive with increased plasma
aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA
(mRNA) for transforming growth factor-beta1 (TGF-beta1) and prepro-epidermal
growth factor (EGF) was measured in liver, heart, and renal glomeruli and
tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed
in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF
beta1 expression in glomeruli, tubules, and heart, but not in liver, and
increased EGF expression in renal tubules only. High-dose ANG II decreased
clusterin expression in liver only. Fibrosis was induced by low- and high-dose
ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively
stimulates TGF-beta1 mRNA in the heart and kidney, which may contribute to
cardiac and renal interstitial fibrosis resulting from activation of the renin
angiotensin system independent of hypertension. By stimulating cellular
proliferation, selective stimulation by ANG II of EGF in renal tubules may
amplify the effects of TGF-beta1. Suppression of clusterin expression in the
liver of hypertensive rats may represent a specific response to high levels of
circulating ANG II or a response to hypertensive injury.
PMID- 9657632
TI - A limited renal injury may cause a permanent form of neurogenic hypertension.
AB - Previously, we have shown that an acute injury to the kidney produced by an
intrarenal injection of phenol causes an immediate increase in blood pressure and
in norepinephrine (NE) secretion from the posterior hypothalamus. The studies
suggest that in this model afferent impulses from the kidney to central
integrative structures in the brain may be responsible for the increase in blood
pressure. To further evaluate whether a renal injury caused by the intrarenal
injection of phenol leads to a permanent elevation of blood pressure and whether
this is mediated by increased sympathetic nervous system activity, we examined
the chronic effects (4 weeks) of an intrarenal injection of 50 microL of 10%
phenol on blood pressure and NE secretion from the posterior hypothalamus.
Systolic blood pressure increased from 128 +/- 2.1 to 176 +/- 1.5 mm Hg (P < .01)
4 weeks after receiving the intrarenal injection of phenol, but it did not change
in rats that received the vehicle (128 +/- 2.4 and 135 +/- 1.7 mm Hg) and in rats
that were subjected to renal denervation (127 +/- 3.4 and 124 +/- 1.0 mm Hg). The
secretion of NE from the posterior hypothalamic nuclei was greater (P < .01) in
rats that received phenol (253 +/- 9.6 pg/mL) than in controls (158 +/- 8.6
pg/mL) and denervated rats (170 +/- 2.1 pg/mL). These studies have shown that a
limited injury to one kidney may cause a permanent elevation of blood pressure
and this is associated with increased sympathetic nervous system activity.
PMID- 9657633
TI - Human leukocyte antigens and malignant essential hypertension.
AB - The purpose of this study was to investigate an association between human
leukocyte antigens (HLA) and the susceptibility to malignant hypertension. The
presence of HLA-A, -B, -DR, and -DQ was determined in 33 white and in 23 mulatto
Brazilian patients with malignant essential hypertension. No statistically
significant differences were detected between patients and control subjects. It
is nevertheless important to note that we have observed an increased frequency of
DR3 in the mulatto patients (34.8% v 21.4%). We consider that this finding
supports the existence of an HLA-DR3 association with hypertension in the black
population, as has been claimed by other authors.
PMID- 9657634
TI - Association between left atrial enlargement and target organ damage in essential
hypertension.
PMID- 9657635
TI - Is sexual dysfunction in hypertensive women uncommon or understudied?
PMID- 9657636
TI - Who manages hypertensive patients? The primary care-hospital interface.
AB - The term hypertension is used loosely to cover the right-hand skew of the blood
pressure frequency distribution. It embraces almost 20% of the population, of
which the major part will fare as well with or without treatment, and a much
smaller group of true patients in whom underlying causes are or will be found,
the causes being mainly genetic. The role of the primary care physicians is in
the initial detection of patients in both groups, and in the reduction of
attributable risk by collectively pushing the blood pressure distribution to the
left. The role of the specialists is effective diagnosis, prognosis, and
management of the more narrowly defined hypertensive patients, to reverse their
high relative risk of complications, ideally at a stage before they become at
high absolute risk.
PMID- 9657637
TI - Detection and control of hypertension in the population: the United States
experience.
AB - Trends in prevalence, awareness, treatment, and control of hypertension in the
adult US population are reported. The data are from the National Health and
Nutrition Examination Surveys (NHANES), carried out in four separate surveys, the
last being NHANES III, 1988-1991. The age-adjusted prevalence of hypertension at
> or = 160/95 mm Hg declined from 20% to 14%, and at > 140/90 mm Hg it declined
from 36.3% to 20.4% in NHANES III. Hypertension awareness increased significantly
to as high as 89% for those with blood pressures > or = 160/95 mm Hg. For all
people with blood pressure > or = 160/95 mm Hg, nearly 64% have it controlled
below that level, but only 29% have their blood pressure controlled below 140/90
mm Hg. Although the data from these surveys are encouraging, there are still too
many people in the United States with uncontrolled hypertension.
PMID- 9657638
TI - Treatment of raised blood pressure in the population: the Canadian experience.
AB - The Canadian Heart Health Survey, in which all 10 Canadian provinces participated
using a standardized protocol, provides data from 23,129 randomly selected
participants. The hypertension component of this survey indicates a prevalence of
22%; among these hypertensives, 59% were aware of their elevated blood pressure
status. The breakdown of aware hypertensives indicates that 16% of those were
treated and controlled, 24% were treated but not controlled, and 19% were neither
treated nor controlled. In terms of drug prescription pattern, angiotensin
converting enzyme inhibitors, including angiotensin II antagonists, command the
maximum market share of 27.7% ($36 million), followed by diuretics, calcium
channel blockers, beta3-blockers, and others. Although hypertension awareness and
control have improved in the past 25 years, sustained efforts are warranted to
control hypertension in Canada.
PMID- 9657639
TI - Treatment of high blood pressure in Germany.
AB - The reunification of Germany has made it possible to compare the health care in
two independently developed social structures. The prevalence of hypertension was
considerably greater in East German men and women, compared with West German men
and women, although salt intake was lower in East Germany than in West Germany.
Cardiovascular mortality was correspondingly greater. A centralized public health
effort was used in East Germany, whereas in West Germany, the activities were
decentralized and to a large extent dependent on private philanthropists. In the
last two decades, cardiovascular mortality declined in West German men and women,
whereas the same was not true for East German men and women. Hypertension
incidence, awareness, treatment, and control have improved slightly in Germany,
but not enough to explain the improved morbidity figures. Twenty percent of men
and women remain unaware of their hypertension, 40% are aware but not treated,
and only half are aware and controlled. Complacency is unjustified in Germany and
much needs to be done.
PMID- 9657640
TI - Hypertension: the United Kingdom experience.
PMID- 9657641
TI - Hypertension: the East European experience.
AB - Some differences (and similarities) between Eastern Europe and the rest of the
Continent are presented regarding the treatment of hypertension. Based on data
from the WHO Monitoring Trends and Determinants in Cardiovascular Diseases
(MONICA) study, the prevalence of hypertension, and the proportion of
uncontrolled hypertension, is clearly higher in Eastern Europe. According to one
local long-term observer, a trend for further increases in prevalence is
discernable. Comparative drug consumption studies are desirable. Regarding
national experiences with hypertension and health care in general, there are also
some important sociocultural differences; anecdotal observations are reported
that support this assertion.
PMID- 9657642
TI - Prevalence, treatment, and control of hypertension in the French population: data
from a survey on high blood pressure in general practice, 1994.
AB - A survey was conducted in a cohort of 235 general practitioners (GP) selected by
Sofres Medical who were representative of the French medical population, to
measure the percentage of patients with hypertension, treated hypertensives and
patients with controlled hypertension. Data were collected over 1 week of office
consultation. Practitioners were initially instructed to use the same type of
mercury sphygmomanometer, equipped with pneumatic cuffs of different sizes. Three
consecutive blood pressure (BP) measurements were made and the last two were
recorded. Practitioners had to carry out their own survey over a period of 1 week
on all patients > 18 years of age who visited their offices. Patients were
considered as hypertensive (HP) if the mean of the two recorded BP measurements
was > or = 140/90 mm Hg or if they were taking antihypertensive drug treatment.
Three cutoff points were used to define controlled hypertension: < 140/90 mm Hg
(overall population of HP), < 160/95 mm Hg (HP < 65 years of age), and < 160/90
mm Hg (HP > or = 65 years of age). Among 12,351 patients (mean age, 48.6 years;
women, 58%), 5020 were HP, (41%) of whom 2035 were without treatment (41%) and
2985 were receiving antihypertensive drug treatment (59%). Two hundred-thirty
patients (4.6%) remained at high risk with moderate or severe hypertension (BP >
or = 180 [systolic] or 105 [diastolic] mm Hg), ie, 1 patient/week/GP. The study
confirms the high prevalence of hypertension in general practice and shows that 7
of 10 patients have an acceptable control of their BP (< 160/95 or < 160/90 mm Hg
according to age) but only 24% of treated HP achieved the target of a BP level <
140/90 mm Hg, representing 28% of the 18 to 64 year old group and 21% of the
elderly group. French GP did not choose an optimal control, and the medical
community is waiting for answers to crucial questions, ie, does optimal BP
control significantly improve the absolute cardiovascular risk? How far should
blood pressure be lowered?
PMID- 9657643
TI - Actions implemented to improve hypertension control in Spain.
AB - Hypertension prevalence is estimated at approximately 30% of the adult population
in Spain, using the 140/90 mm Hg cutoff. This represents a heavy public health
burden when compared with other European countries, although the direct cost per
person is one of the lowest in Europe. The programs implemented regionally since
1985 are presented here. As a result of them, a decade later the number of
hypertensives with controlled blood pressure has increased from 10% in 1986 to
13% in 1995, and cerebrovascular mortality has steadily decreased.
PMID- 9657644
TI - Change in cerebral glucose metabolism during limbic seizures elicited from
lateral septal nucleus.
AB - The roles of the amygdala and hippocampus have been extensively studied in limbic
seizures. Although the septal nuclei have a close connection to the hippocampus
and affect emotional behavior, the effect on limbic seizures is still unclear. We
have reported that characteristic sham-rage seizures were observed in cats, by
administering a local injection of kainic acid (KA) into the lateral septal
nucleus (LSN). This study investigated the electrophysiological features of KA
induced septal seizures in rats and analyzed the process in relation to the
cerebral glucose metabolism using [14C]deoxyglucose autoradiography. On EEG,
epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus
and the amygdala. Behavioral change was similar to that in limbic seizures
induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats.
However, the local cerebral glucose metabolism during the seizures increased not
only in the limbic structures including the LSN but also in the hypothalamus and
periaqueductal grey matter of the midbrain. The findings were distinctive of
septal seizures as compared with amygdaloid seizures. The results suggested that
sham-rage seizures in cats might be caused by a secondary epileptogenic
excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The
septal nuclei may play an important role in emotional behavior associated with
limbic seizures even if there is a species difference in its function.
PMID- 9657645
TI - Intracortical functional heterogeneity in area striate during penicillin-induced
spikes in rabbits.
AB - The generation and spread of epileptiform activity within the cortex depend on
the functional and anatomical relationships between the focus and its surrounding
area. These processes are not completely understood. Thus intracortical current
source-density analysis (CSD) was performed in six rabbits in order to
investigate this functional relationship. Electric potential was measured
perpendicular to the cortical surface by means of two 16-channel probes, and CSD
was calculated within the focus and at various distances of up to 5 mm. The
cortical areas surrounding the focus could be subdivided into three regions. The
region up to 3 mm from the focus showed similar activity but beyond 4.5 mm no
characteristic functional relationship was found with regard to the epileptiform
events within the focus. Within the region 3.5-4.5 mm, however, mainly
supragranular cells seem to contribute to the electric potential measured at the
cortical surface and within the extracellular space. They were activated
simultaneously with the initiation of focal spike generation. Taking into account
the distribution of the electric potential and the results of CSD analysis, these
cells seem mainly involved in the inhibition of the horizontal spread of spike
activity.
PMID- 9657646
TI - Histaminergic mechanisms in amygdaloid-kindled seizures in rats.
AB - The present study was undertaken to clarify the role of histaminergic neuron
system on amygdaloid kindled seizures in rats. A significant decrease in
histamine contents in the amygdala was observed after development of amygdaloid
kindling. Histidine and metoprine inhibited amygdaloid kindled seizures at doses
causing an increase in histamine contents of the brain. H1-antagonists
(diphenhydramine and chlorpheniramine) attenuated histidine-induced inhibition of
amygdaloid kindled seizures, however no significant antagonism was observed with
H2-antagonists (zolantidine and ranitidine). The development of amygdaloid
kindling was retarded by repeated administration of histidine. These findings
suggest that histaminergic mechanisms play a suppressive role in amygdaloid
kindled seizures through histamine H1-receptors.
PMID- 9657647
TI - Evaluation of the anticonvulsant profile of progesterone in male amygdala-kindled
rats.
AB - While there is clinical evidence that progesterone has anticonvulsant activity in
women with complex partial seizures, previous studies on the anticonvulsant
effect of progesterone in experimental animal models are inconclusive. Moreover,
the effect of progesterone on seizure parameters in fully amygdala-kindled rats
which best resemble complex partial seizures has not been evaluated. Therefore,
in the present work the anticonvulsant effect of progesterone at doses of 10, 30,
60 and 75 mg/kg in fully amygdala-kindled male rats was studied. Only at the high
and sedative dose of 75 mg/kg, progesterone suppressed behavioral seizures and
afterdischarges elicited 10 min after intraperitoneal (i.p.) administration.
Pretreatment with the progesterone antagonist, 17beta-hydroxy-11beta-(4
dimethylaminophenyl)-17alpha-(prop- 1-ynyl)-estra-4,9-dien-3-one (RU 38486) at
the dose of 3 mg/kg did not inhibit the anticonvulsant activity of progesterone,
while pretreatment with the GABA(A) receptor antagonist, bicuculline (2 mg/kg)
blocked the anticonvulsant effect of progesterone. Neither RU 38486 nor
bicuculline had any effect on the seizure parameters. These findings suggest that
only at large and sedative doses, progesterone has some anticonvulsant activity
in male amygdala-kindled rats which may be partly mediated via the GABA(A)
receptor complex interaction.
PMID- 9657648
TI - Acute heat stress model of seizures in weanling rats: influence of prototypic
anti-seizure compounds.
AB - The present study tested the therapeutic potential for prototype anti-epilepsy
drugs using an animal model of infantile febrile seizures. The model consisted of
immersion of weanling rats (21 days old) in a 45 degrees C water bath for a
maximum of 4 min (four exposures over a 2 week period) and observing for the
progression to stage-5 seizures. All compounds were administered orally at the
respective ED50 for prevention of seizures in the maximal electroshock (MES)
test. Clonazepam effectively lowered the score for seizure grade, shortened the
duration of seizures, as well as reduced the number of animals experiencing
seizures during three of the four testing periods. MK801 reduced both the maximum
seizure grade, and the number of animals experiencing seizures during sessions
two and three. However, the dose of MK801 caused behavioral side effects.
Valproate actively decreased seizure grade, while it modestly acted to attenuate
seizure duration, extended the time to seizure onset, and reduced the number of
animals experiencing seizures on testing day 1. Remacemide hydrochloride and
phenobarbital were not effective. The method appears useful for evaluating the
potential of agents to prevent acute febrile seizures.
PMID- 9657649
TI - Frontal versus transcorneal stimulation to induce maximal electroshock seizures
or kindling in mice and rats.
AB - Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on
the skin of the intact frontal skull of mice or rats, may represent a more humane
alternative to the widely used transcorneal stimulation to induce electroshock
seizures. The aim of this work was to directly compare transcorneal and frontal
stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and
the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus
produced seizures. In addition, we stimulated mice and rats repeatedly via
transcorneal and frontal electrodes to see whether kindling is produced by this
procedure. Two electroshock tests were used in mice, i.e. maximal electroshock
seizure threshold (MEST) test and MES generated by supramaximal stimulation (50
mA). Frontal stimulation resulted in lower convulsive threshold than in the case
of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in
seizure threshold for both sites of stimulation, i.e. transcorneal and frontal.
As regards type of electrodes, higher doses of PHT were required to increase
seizure threshold in the case of frontal than transcorneal stimulation.
Supramaximal stimulation (50 mA) yielded comparable ED50 values regardless of the
site of stimulation. Furthermore, once-daily stimulation of mice, regardless of
the placement of electrodes, did not induce any changes in convulsive threshold.
We also attempted to kindle mice and rats via corneal and frontal electrodes by
repetitive electrical stimulation using currents which initially did not produce
generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA
(corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice
daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With
corneal stimulation in rats there was a clear progression of kindling development
which was not the same in nature when compared with corneally-stimulated mice.
Frontal stimulation did not produce kindling. Moreover, corneal stimulation was
better tolerated by rats, while in mice high mortality was seen after either
method of current delivery. Our data indicate that frontal electrodes can be used
as an alternative to transcorneal stimulation to produce MES by supramaximal or
threshold current intensities as screening procedures in antiepileptic drug (AED)
development. Nevertheless, this type of stimulation cannot be used to produce
minimal electroshock seizures and seems not to be useful to produce kindling in
rats and mice.
PMID- 9657650
TI - The relationship between seizure frequency, seizure type and quality of life:
findings from three European countries.
AB - Understanding the relationship between seizure frequency, seizure type and scores
obtained from quality of life (QOL) measures is important if the incorporation of
QOL measures into epilepsy clinical trials is to become standard practice. There
is also a need to consider cross-cultural differences obtained from QOL measures,
particularly in the context of multicentre international trials. In this study,
300 patients recruited from UK, Germany and France completed the Functional
Status Questionnaire (FSQ); information about patients' clinical and demographic
status was also collected. Results from the study highlighted that seizure type
and seizure frequency, as well as country of origin, were significant predictors
of scores on the FSQ. It is important to measure the effect of seizure type, not
just seizure frequency, on QOL when testing for differences between antiepileptic
therapies in the context of clinical trials.
PMID- 9657651
TI - Hyponatremia induced by oxcarbazepine in children.
AB - We report the case of a 12-year-old girl with severe clinically relevant
hyponatremia (118 mmol/l) and hypochloremia (81 mmol/l) during treatment with
oxcarbazepine (OCBZ). The adverse effects were rapidly reversible after
discontinuation of OCBZ and did not occur when exposed to carbamazepine. We
reviewed the charts of 48 patients who received OCBZ as in-patients in our
epilepsy centre and found hyponatremia in nine and hypochloremia in four. The
mean sodium level of all patients was 139 mmol/l (range 118-150 mmol/l). We did
not see any correlation between sodium or chloride levels and dose of OCBZ or
blood serum level of the active metabolite 10-OH-carbazepine. We emphasize that
children are at risk of developing electrolyte disturbances during treatment with
OCBZ and thus the level of at least sodium should be monitored in those patients.
PMID- 9657652
TI - High incidence of epilepsy related to onchocerciasis in West Uganda.
AB - The incidence of epilepsy was assessed in an onchocerciasis endemic area in West
Uganda over a period of 4 years. A high overall crude incidence rate of 215 per
100000 person-years was found (age-adjusted: 156 per 100000 person-years) and the
incidence in zones of high onchocerciasis endemicity was significantly higher
than in low endemic zones (age adjusted rates: 232 per 100000 person-years versus
77 per 100000 person-years; Yates corrected chi2: P < 0.01). The data constitute
a baseline for an ongoing intervention study on the effects of onchocerciasis
control on epilepsy incidence in the study area. If a causal relationship between
onchocerciasis and epilepsy can be confirmed, this would have significant
implications for the concept of morbidity due to onchocerciasis and for the
prevention of epilepsy in the endemic areas.
PMID- 9657653
TI - Central sleep apnoea and heart failure (part II).
AB - Central sleep apnoea (CSA) in congestive heart failure is sleep state dependent
and occurs typically in stages I and II of non-REM sleep. The pre-requisites are
hypocapnia and some prolongation of the circulation time. It is not certain
whether abnormalities in after-discharge activity in the brainstem are also
important. The presence of CSA in patients with left ventricular dysfunction is a
poor prognostic sign and associated with a higher mortality in that group
compared to age, sex and ejection fraction matched patients with congestive
cardiac failure alone. It is reasonable to speculate that the CSA causes an
increase in sympathetic nervous system activity which would maintain afterload at
a high level or tend to increase it with time. The application of a high
afterload to an impaired left ventricle leads over time to a further reduction in
ejection fraction. From other studies, particularly ACE inhibitor studies, it is
known that ejection fraction and prognosis are almost linearly related. It could
therefore be said that once CSA has developed it may lead to a vicious circle of
increasing afterload and further reduction in ejection fraction, causing
worsening CSA and further increases in afterload. A number of treatments have
been shown to be of benefit: supplemental nocturnal oxygen therapy, acetazolamide
and nasal CPAP therapy have all been shown to reduce CSA. In addition nasal
continuous positive airways pressure (CPAP) has been shown by two groups in
Canada to also improve ejection fraction. The beneficial effects on ejection
fraction in particular, persist after the treatment has been withdrawn, which
suggests either remodelling of the left ventricular musculature or a resetting of
the baseline sympathetic nervous system activity. The impressive increase in
ejection fraction due to three months nasal CPAP therapy in one study (an average
35% increase) is both dramatic and exciting for the future. It is reasonable to
expect improvement in prognosis for patients with CCF whose ejection fraction
rises with CPAP treatment. Finally, only a limited number of studies have been
published. Unfortunately the impressive results from Canada have not yet been
reproduced in other centres around the world.
PMID- 9657654
TI - The effect of inhaled budesonide on the diurnal variation in airway mechanics,
airway responsiveness and serum neutrophil chemotactic activity in Asian patients
with predominant nocturnal asthma.
AB - The effectiveness of inhaled corticosteroids in the control of daytime symptoms
in asthma is well established, but the specific use against nocturnal asthma has
not been systematically studied in Asian patients. This study examined the effect
of treatment with inhaled budesonide on the nocturnal variation in measurements
of airway calibre, bronchial hyperresponsiveness to inhaled histamine and
circulating neutrophil chemotactic activity in Asian patients with nocturnal
asthma. Thirty patients, with nocturnal asthma, were randomized into a 2-month,
double-blind, parallel group study. Twice as many subjects were allocated to the
group who received two consecutive months of inhaled budesonide 1600 microg daily
as to the group who received placebo followed by budesonide. Spirometry, lung
mechanics, bronchial hyperresponsiveness and serum neutrophil chemotactic factor
(NCA) were measured at 16.00 h, 22.00 h and at 04.00 h on 3 days and nights, 4
weeks apart before and after either placebo or budesonide. The combined
measurements for the two groups at 04.00 h before and after treatment with
budesonide were: forced expiratory volume in 1 s (FEV1) mean (SEM) litres 1.34
(0.17) before, 2.00 (0.19) after; thoracic gas volume (TGV) litres 3.05 (0.32)
before, 2.25 (0.14) after; specific airway conductance (sGaw) (cmH20.0 sec)(-1)
0.39 (0.07) before, 1.16 (0.17) after; PD20 microg geometric mean 1.16 before,
44.74 after; neutrophil chemotactic activity (NCA) in units of graduations of
migration 98.8 (4.2) before, 101 (14.2) after. The data showed that short and
intermediate term high dose inhaled budesonide is an effective specific treatment
for nocturnal asthma in Asian patients, resulting in marked improvements in
symptoms and in lung mechanics, and reductions in the diurnal variations in
bronchial hyperresponsiveness, before any change could be demonstrated in a
circulating marker of airway inflammation.
PMID- 9657655
TI - Simultaneous continuous 13C, 12C analysis of expired gas in the 13C breath test.
AB - The 13C breath test is a method of clarifying the metabolism of loaded substances
by administering 13C-labelled materials and calculating the 13CO2 and 12CO2 ratio
(13C/12C isotope ratio) in the expired gas. The materials are metabolized and
expelled in the expired gas. Because simultaneous continuous measurement of 13CO2
and 12CO2 in expired gas has been difficult up to the present, respective expired
gases, including dead space before and after administration, have been sampled to
separate sampling bags and 13C/12C has been measured in the bags and changed
fraction of 13C/12C after administration (delta) has been used to judge the
metabolic process. This method is affected by the contamination of the dead space
gas. In the present study, in order to exclude the dead space effect,
simultaneous continuous analysis of 12CO2 and 13CO2 of expired gas identifying
alveolar gas was applied to the 13C-urea breath test in addition to the
conventional sampling bag method. Both isotope detectors were attached to a mass
spectrometer. Fifty-six cases receiving stomach health check-ups for Helicobacter
pylori were examined. Delta was calculated in the bag or in phase III of
continuous gas measurement. Because the bag contains dead space, delta was
reduced and sensitivity and specificity with reference to gastric fluoroscopy or
Helicobacter pylori IgG antibody were reduced. Decreasing the dead space
contamination is important in reducing the measurement error in the 13C breath
test and simultaneous continuous measurement is a good tool for this purpose.
PMID- 9657656
TI - Reversible airway obstruction in rheumatic mitral valve disease.
AB - Lung function was studied in 24 patients with advanced mitral stenosis scheduled
for mitral valve replacement (MVR), and revealed an obstructive ventilatory
pattern. Forty per cent of the patients had a forced expiratory volume in 1 s
(FEV1)<60% of that predicted in the preoperative period. Twenty-five per cent of
those operated upon showed a similar pattern up to 110 weeks postoperatively. A
blind study of the effect of placebo and beta2 agonist (salbutamol) inhalation
was performed preoperatively and 6 months postoperatively, to evaluate the
reversibility of airflow obstruction in these patients, flow volume curve and
body plethysmographic measurement of airway resistance (Rex) and intrathoracic
gas volume (VTG). Patients in the pre and postoperative period showed a
significant difference between the placebo and the beta2 agonist responses for
FEV1, FEV1 as percentage of FVC (FEV1% FVC), peak expiratory flow rate (PEFR),
flow rate of 50% of expiratory vital capacity (Vmax50), Rex and VTG (P<0.001). We
conclude that salbutamol inhalation improves obstructive impairment in patients
with MVR pre- and postoperatively.
PMID- 9657657
TI - Computed tomographic findings of environmental asbestos-related malignant pleural
mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is not an infrequent fatal neoplasm. It is
endemically present in some regions of Turkey due to its aetiological
relationship to exposure to environmental fibrous minerals. The aim of this study
was to determine the thorax computed tomographic (CT) features of environmental
asbestos-related MPM. In this study, we examined retrospectively the CT scans of
46 untreated patients with pathological diagnosis of environmental asbestos
related MPM among 151 patients with malignant pleural mesothelioma in the Izmir
Chest Disease and Surgery Hospital. The CT scans were interpreted by consultation
of four observers. Malignant pleural mesothelioma was unilateral in 45 (97.2%) of
the patients. Pleural effusions were found in 42 (91%) of the patients, pleural
calcifications in 12 (26%), contracted hemithorax in 14 (30%), interlobar fissure
involvement in 25 (54%) and mediastinal pleural involvement in 26 (57%). A
contracted hemithorax was significantly correlated with pleural rind
configuration. Pleural thickenings were found in 45 (99%) of the patients.
Pleural thickenings were in the form of nodularity in 10 (22%) cases, regular in
12 (27%) cases, as a focal mass in 3 (7%) cases and as a pleural rind in 20 (44%)
cases. Pleural thickening was greater than 1 cm in 32 (71%) cases. The most
common CT findings in our series were unilateral circumferential pleural
thickening, nodular pleural thickening, pleural thickening greater than 1 cm and
mediastinal pleural involvement. Generally, pleural effusion was accompanied by
this. There was interlobar fissure involvement in half of the patients. There was
no pathognomonic CT finding in environmental asbestos-related MPM. But CT was
useful in suggesting the diagnosis of malignant pleural disease in the cases with
MPM.
PMID- 9657658
TI - Angiotensin converting enzyme inhibitor cough: lessons from heart-lung
transplantation.
AB - Coughing is a frequent side-effect of angiotensin converting enzyme (ACE)
inhibitors. Its pathogenesis is thought to be related to the local accumulation
of tachykinins although the role of extrinsic cholinergic pathways is unclear.
The development of an ACE inhibitor induced cough in two patients who have
undergone heart-lung transplantation and in whom cholinergic pathways remain
denervated supports the hypothesis of a 'local' mechanism.
PMID- 9657659
TI - Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia.
AB - A 31-year-old male was diagnosed as having chronic myelogenous leukaemia and has
been treated with hydroxyurea and interferon-alpha since February 1995. After 16
months, he complained of low-grade fever and a cough. Bilateral hilar lymph node
enlargement was detected on the chest X-ray film and multiple subcutaneous
erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid
granuloma. Two months after the cessation of interferon therapy, the subcutaneous
nodules and the hilar lymph node enlargement resolved. It is possible that
continuous interferon administration can promote granuloma formation in
sarcoidosis by activating T cells and macrophages.
PMID- 9657660
TI - Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting
enzyme inhibitor-induced cough.
AB - The role of genetic factors was reviewed with respect to the pathophysiology of
bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme
(ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked
to atopy but is associated with serum IgE levels. The beta2-adrenergic receptor
gene on 5q32-33 was found to have polymorphism by Ban I and to be related to
beta2-receptor function; a defect of a 2.3 kb allele is related to lowered
sensitivity to beta2-agonists. This defect is also related to higher prevalence
on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to
Gly) of beta2-receptors was lower and Gln27 to Glu mutation is extremely rare in
the Japanese population compared with Caucasians. There is polymorphism of ACE
genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The
genotype is a significant determinant of serum ACE activity and may determine the
prognosis of sarcoid patients. Genotype II has a higher incidence of coughing
induced by ACE inhibitors.
PMID- 9657661
TI - Management of non-small cell lung cancer according to staging--an update.
AB - The treatment of non-small cell lung cancer (NSCLC) depends on staging based on
tumour (T), nodal (N) and metastasis (M) descriptors. Stages I and II tumours are
potentially curable with surgery alone. Stage IIIA T3 tumours are also
potentially operable. Preoperative chemotherapy appears promising in downstaging
stage IIIA disease to enable surgical resection. Recent meta-analyses did not
support the use of postoperative chemotherapy for stages I, II and IIIA diseases,
but were supportive of the use of cisplatin-based chemotherapy in stage IIIA N2
disease (+ radiotherapy), stage IIIB disease (+ radiotherapy) and in metastatic
stage IV disease in improving survival. New chemotherapy agents available over
the past few years would further improve the efficacy of chemotherapy in NSCLC.
PMID- 9657662
TI - Tumour-infiltrating lymphocytes in non-small cell lung cancer are activated T
lymphocytes.
AB - This study was carried out in order to investigate the local immune reaction of
tumour-infiltrating lymphocytes (TILs) in the primary tumours of non-small cell
lung carcinomas. Thirty non-small cell lung cancer (NSCLC) patients were
included. The tumour tissue was taken at thoracotomy and monocellular suspension
of the tumour was obtained by mechanical disaggregation. Dual-coloured flow
cytometric analysis of TILs and their corresponding peripheral blood lymphocytes
(PBLs) was performed. Tumour-infiltrating lymphocytes contained significantly
higher proportions of CD3(+) T lymphocytes and CD8(+) T lymphocytes than the
corresponding PBLs (82.0%+/-13.9% vs 66.3%+/-10.6% for CD3, P<0.001; 39.0%+/
18.4% vs 26.4%+/-5.2% for CD8, P<0.001). Tumour-infiltrating lymphocytes
contained significantly higher proportions of activated memory lymphocytes than
PBLs did (9.8%+/-8.6% vs 1.3%+/-1.5% for CD25, P<0.001; 40.5%+/-30.2% vs 10.2%+/
14.8% for CD71, P<0.001; 75.5%+/-11.9% vs 28.6%+/-9.8% for HLA-DR, P<0.001).
These findings were also found in both CD4(+) TILs and CD8(+) TILs. The TILs of
NSCLC contained higher proportions of T lymphocytes and CD8(+) lymphocytes than
their corresponding peripheral bloods. The proportions of activated memory
lymphocytes were also significantly higher in the TILs, both in CD4(+) TILs and
CD8(+) TILs, than the corresponding PBLs.
PMID- 9657663
TI - Postnatal development of urea synthesis capacity in preterm infants with
intrauterine growth retardation.
AB - The postnatal development of the urea-synthesizing capacity was studied in 21
preterm infants with intrauterine growth retardation (IUGR) and compared with
results found in 12 infants without IUGR as controls. The urea-synthesizing
capacity was estimated by the ratio Q of 15N abundance of ammonia and urea in 6
hour urine samples collected after enteral administration of 3 mg [15N]H4Cl/kg
body weight. The measurements were performed on the first day when a protein
intake of 3.0-3.5 g/kg/day and an energy intake of 120 kcal/kg/day were tolerated
(study day 1: postnatal 14-21 days) and on the day of discharge from the hospital
(study day 2: postnatal age 39-56 days). The group of infants with IUGR was
subdivided in one group of infants who developed catch-up growth (n = 12) and one
group who did not demonstrate catch-up growth (n = 9). On study day 1, the Q
values of the IUGR infants without catch-up growth were significantly higher than
those of the IUGR infants with catch-up growth (13.4 +/- 2.3 vs. 9.2 +/- 2.2) or
of the control infants without IUGR. During the time period from study day 1 to
study day 2 the Q values of the IUGR infants with catch-up growth decreased
significantly (9.2 +/- 2.2 vs. 4.8 +/- 2.0; p < 0.001) and were in the range of
the control infants without IUGR. In contrast, the Q values of the IUGR infants
without catch-up growth did not significantly change during the study period
(13.4 +/- 2.3 vs. 11.3 +/- 2.8; p = 0.097). On both study days there was a
significant correlation between the Q values and the degree of IUGR (study day 1:
r = 0.652, p < 0.01; study day 2: r = 0.842, p < 0.001). The data indicate that
the urea-synthesizing capacity of preterm infants increases during early
postnatal life and that severe IUGR may impair this development. Metabolic
investigations using urea as marker for evaluation of optimal quantity or quality
of dietary proteins should carefully be interpreted when infants with severe IUGR
are studied.
PMID- 9657664
TI - Epidemiology of neonatal acute respiratory disorders. A multicenter study on
incidence and fatality rates of neonatal acute respiratory disorders according to
gestational age, maternal age, pregnancy complications and type of delivery.
Italian Group of Neonatal Pneumology.
AB - A prospective 3-month survey of neonatal respiratory disorders in 17,192 Italian
infants born in 65 hospitals, located in 17 Italian regions representative of
northern, central and southern Italy, was performed to evaluate the incidence of
neonatal acute respiratory disorders and their risk factors. The prematurity rate
was 7.3%, while the extremely low birth weight (< 1,000 g) and very low birth
weight (< 1,500 g) rates were 0.58% and 0.99%, respectively. Four hundred and
ninety-one infants (2.8%) developed respiratory signs. Lethality or specific
fatality rate (SFR) for acute respiratory disorders with regard to the overall
study population was 0.45%. The male/female ratio of affected infants was 1.3:1.
Among affected newborns the case fatality rate (CFR) for respiratory disorders
was 15.88% (78/491) and was higher in males than in females (2:1), in infants
with a gestational age of < or = 28 weeks (60%) and birth weights of < 1,000 g
(50%). Moreover, the SFR was higher (p < 0.05) in the infants of mothers older
than 34 years. SFR was 3.0% in intrauterine growth-retarded infants, 3.6% in the
first twin and 3.2% in the second twin. An Apgar score of < or = 3 at 5 min was
strongly related to the incidence of respiratory disorders (47.1%). The antenatal
prevention of neonatal respiratory distress syndrome with maternal corticosteroid
treatment was performed in 84% of newborns (< 32 weeks) with respiratory problems
in northern Italy, and about 25% and 38% in central and southern Italy,
respectively. The CFR was double in southern Italy as compared with northern and
central Italy. Prematurity, low birth weight and a low Apgar score (< or = 3) at
1 and 5 min as well as a maternal age of > 34 years are risk factors for acute
respiratory disorders.
PMID- 9657665
TI - Different patterns of sighs in neonates and young infants.
AB - To examine the prevalence and clinical assessment of sighs in neonates, we
observed three different patterns of sighs: (A) sighs in the absence of apneic
pause; (B) sighs with instantly following apneic pause >2 s, and (C) sighs with
apneic pause >2 s following 1-3 normal breaths. We investigated preterm and term
infants with 12 h nocturnal polygraphic recording. Sighs were more frequent in
preterm than in term infants and more so during REM sleep than non-REM sleep. The
part of sighs B of total number of sighs increased with gestational age. During
REM sleep sighs without apnea were predominant, whereas apnea-associated sighs
were mainly found during non-REM sleep.
PMID- 9657666
TI - Nitric oxide modulates premature renal circulation in hypoxic newborn piglets.
AB - We studied the role of nitric oxide (NO) on the regulation of blood flow in the
immature kidney during hypoxia, resuscitation and the recovery period using the
NO inhibitor N(omega)-nitro-L-arginine (L-NNA) in a newborn piglet model, and the
possibility of urinary cGMP as an index of renal function. After administration
of L-NNA, the blood flow in both the cortex and medulla significantly decreased,
indicating that NO is constantly released to maintain renal circulation. During
hypoxia, the renal blood flow fell remarkably, and there were no differences
between the control and L-NNA groups. During the post-resuscitation period, the
recovery of renal blood flow was significantly suppressed in L-NNA
administration, and it was speculated that NO might be an important factor for
recovery of circulation from vasoconstriction due to hypoxemia. Urinary cGMP/cr
was significantly increased on recovery from hypoxemia and was suppressed by L
NNA administration. This result suggested that the change in cGMP/cr represents
renal blood flow change. We conclude that NO may play an important role in
maintaining basal hemodynamics, and may also be a crucial factor for recovery
from post-hypoxic vasoconstriction in premature kidneys. Urinary cGMP/cr might
serve as one of the indices for assessment of premature renal circulation.
PMID- 9657667
TI - Effect of dietary n-3 fatty acids on hypoxia-induced necrotizing enterocolitis in
young mice. n-3 fatty acids alter platelet-activating factor and leukotriene B4
production in the intestine.
AB - Necrotizing entercolitis (NEC) is an important neonatal disease with a high
mortality rate. Inflammatory mediators, such as mainly platelet-activating factor
(PAF), leukotrienes (LT) and tumor necrosis factor play an important role in the
genesis of NEC. Diets in omega-3 (n-3) fatty acids appear to have an
antiinflammatory effect, which is thought to be due to decreased active
prostaglandins and leukotrienes production after incorporation of these fatty
acids into cell membrane phospholipids. We investigated the protective effect of
fish oil (source of n-3 fatty acids) on hypoxia-induced model of NEC. Young mice
were divided into three groups; group 1 mice were fed standard chow (n-3 fatty
acids-free), group 2 was fed a chow supplemented by 10% fish oil for 4 weeks.
Group 3 mice served as control. We examined the intestinal lesions by light
microscopy and measured intestinal tissue PAF and LB4 levels in hypoxia-induced
model of NEC. Significantly increased intestinal PAF and LTB4 levels were found
in group 1 mice when compared to group 2 and group 3 mice. The histopathology of
the intestinal lesions in group 1 animals was characteristic of ischemic injury.
In the n-3 fatty acids-supplemented animals these lesions were milder. The
present study shows that endogenously released PAF and LTB4 play an important
role in mediating hypoxia-induced intestinal necrosis. The present study also
suggests that dietary supplementation with n-3 fatty acids suppress intestinal
PAF and LTB4 generation in hypoxia-induced bowel necrosis. The intestinal
protective effect of n-3 fatty acids in an experimental model of NEC may open new
insight into the treatment and prevention of NEC in neonates.
PMID- 9657668
TI - Pharmacodynamic effects and pharmacokinetic profile of continuous infusion
fentanyl in newborn piglets.
AB - The objective of this study was to determine hemodynamic effects and
pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old
newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl
at 30 microg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10
microg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus
and infusion of 5% dextrose. Blood samples were obtained serially from systemic
circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and
blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion
both in the systemic (202.7 +/- 39.1 ng/ml) and sagittal sinus vein (136.7 +/-
20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h.
Heart rate was significantly elevated at 30 min and 6 h during infusion but
systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and
sagittal sinus vein PO2 were significantly decreased from 2 through 6 h of
infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in
sagittal sinus vein O2 content at 30 min of infusion, an effect which lasted up
to 6 h (47%, p < 0.01). Fractional O2 extraction by the brain increased
significantly at 30 min (26%, p < 0.01) and remained elevated throughout the
infusion time (22%, p < 0.05 at 6 h). Brain fractional O2 extraction increased as
a function of brain fractional fentanyl extraction (r2 = 0.40, p < 0.001). Mean
clearance was estimated as 56.2 +/- 13.7 ml/kg/h (range 43.5-76.9 ml/kg/h), mean
volume of distribution at steady state was 1.29 +/- 0.6 liters/kg (range 0.78
2.15 liters/kg) and the mean half-life was 15.7 +/- 5.7 h (range 9.4-22.5 h).
These data suggest that increased systemic oxygen may be necessary to maintain
normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.
PMID- 9657669
TI - Responses to stress and novelty in adult rats born vaginally, by cesarean section
or by cesarean section with acute anoxia.
AB - The aim of this study was to test the hypothesis that alterations in birth
conditions, specifically vaginal birth vs. birth by Cesarean section (C-section)
vs. birth by C-section with an added period of acute global anoxia, produces long
term differences in behavioral responses to stress or novelty in the rat at
adulthood. In comparison to animals born by rapid C-section alone, animals born
by C-section with 10 or 15 min of added anoxia were significantly more immobile
during forced swim stress administered for 6 trials over several weeks. In a step
down passive avoidance task, there were no group differences in acquisition or
retention of the avoidance response. However, when initially placed in the
passive avoidance apparatus before delivery of shock, animals born by C-section
with 15 min of anoxia required significantly more pretrials to step down from the
wooden platform, than did vaginally born or C-sectioned animals. No group
differences were observed on measures of exploratory behavior in an elevated plus
maze or of approach behavior either to food or to a novel object in an open
field. These findings suggest that birth conditions which include a degree of
perinatal hypoxia can contribute to variability in selective responses to stress
and novelty in the adult rat.
PMID- 9657670
TI - Developmental changes in the calcium sensitivity of rabbit cranial arteries.
AB - The present experiments examine developmental changes in cerebrovascular Ca2+
sensitivity. Common carotid (COM), basilar (BAS) and femoral (FA) arteries from
adult (n = 16), 8- to 9-day-old (n = 15) and 24- to 25-day-old rabbits (n = 12)
were denuded of the endothelium and permeabilized with beta-escin. Bath calcium
concentrations were controlled via EGTA-Ca2+ buffer solutions. Adult pCa-force
relations were right-shifted relative to those of 8- to 9-day-old rabbits but
were similar to those of 24- to 25-day-olds. Adult pD2 (-log ED50) values for
Ca2+ averaged 6.36 +/- 0.03 (COM), 6.77 +/- 0.04 (BAS) and 6.40 +/- 0.04 (FA).
Corresponding 8- to 9-day-old values were 6.85 +/- 0.03, 7.08 +/- 0.08 and 6.76
+/- 0.05. In all arteries studied, the addition of 5-hydroxytryptamine (5-HT)
subsequent to contraction by a constant submaximal (EC30) concentration of Ca2+
produced a dose-dependent and GDP3S-sensitive increase in tension attributable to
an increase in Ca2+ sensitivity. The magnitudes of 5-HT-induced increases in Ca2+
sensitivity were significantly greatest in 8- to 9-day-old rabbits, intermediate
in 24- to 25-day-old rabbits, and least in adults. GTPgammaS mimicked the effects
of 5-HT and prevented further increases in Ca2+ sensitivity induced by 5-HT in
all arteries from all age groups. GDPbetaS completely reversed all effects of 5
HT on Ca2+ sensitivity. From these data we conclude that baseline Ca2+
sensitivity is elevated in newborn relative to adult rabbits, at least in
femoral, common carotid and basilar arteries. In these arteries, 5-HT can
increase Ca2+ sensitivity via a G-protein-dependent mechanism which is more
effective in neonatal than adult arteries. These effects of maturation on
vascular Ca2+ sensitivity may play an important role in developmental changes in
vascular reactivity.
PMID- 9657671
TI - Biotin plasma levels of the human fetus.
AB - Biotin is an important vitamin for cellular function and growth and, therefore,
essential for fetal development. The fetus is exclusively dependent on maternal
biotin supply. Since biotin is not produced within the body, maternal biotin
levels depend on dietary intake. In order to investigate the biotin status of the
human fetus, we measured the plasma biotin levels in 15 pregnant women and their
fetuses who underwent amniocentesis and fetal blood sampling at 18-24 weeks of
gestation for prenatal diagnosis of thalassemia. Maternal biotin was found to be
131 +/- (SD) 102 ng/l and fetal biotin 784 +/- 327 ng/l (p < 0.0001). Our
findings are indicative of an active transport mechanism of biotin through the
placenta in favor of the fetus.
PMID- 9657672
TI - Deoxyribose phosphate excision by the N-terminal domain of the polymerase beta:
the mechanism revisited.
AB - DNA polymerase beta (Pol beta) is one of the key enzymes in the base excision
repair pathway. The amino-terminal 8 kDa domain of Pol beta has an activity for
excising a 5'-deoxyribose phosphate (dRP) group from preincised
apurine/apyrimidine (AP) sites. Recent biochemical studies have identified the
catalytic center of the 8 kDa domain and provided new insight into the mechanism
of DNA repair by DNA polymerase beta. By incorporating both structural and
biochemical data, we present here a reaction mechanism for the 5'-dRP excision
activity of the 8 kDa domain. This mechanism focuses on a catalytic groove near
the helix-hairpin-helix (HhH) motif of the 8 kDa domain. Our model shows that the
dRP group of the AP site can be stabilized in the catalytic groove through
extensive interactions with the residues of the groove and be positioned close to
the active center, Lys72, which catalyzes a beta-elimination reaction by forming
a Schiff base with the C1' of the dRP group.
PMID- 9657673
TI - Cocrystal structure of protein farnesyltransferase complexed with a farnesyl
diphosphate substrate.
AB - Protein farnesyltransferase (FTase) catalyzes the transfer of the hydrophobic
farnesyl group from farnesyl diphosphate (FPP) to cellular proteins such as Ras
at a cysteine residue near their carboxy-terminus. This process is necessary for
the subcellular localization of these proteins to the plasma membrane and is
required for the transforming activity of oncogenic variants of Ras, making FTase
a prime target for anticancer therapeutics. The high-resolution crystal structure
of rat FTase was recently determined, and we present here the X-ray crystal
structure of the first complex of FTase with a FPP substrate bound at the active
site. The isoprenoid moiety of FPP binds in an extended conformation in a
hydrophobic cavity of the beta subunit of the FTase enzyme, and the diphosphate
moiety binds to a positively charged cleft at the top of this cavity near the
subunit interface. The observed location of the FPP molecule is consistent with
mutagenesis data. This binary complex of FTase with FPP leads us to suggest a
"molecular ruler" hypothesis for isoprenoid substrate specificity, where the
depth of the hydrophobic binding cavity acts as a ruler discriminating between
isoprenoids of differing lengths. Although other length isoprenoids may bind in
the cavity, only the 15-carbon farnesyl moiety binds with its C1 atom in register
with a catalytic zinc ion as required for efficient transfer to the Ras
substrate.
PMID- 9657674
TI - Solution structure of the B-Myb DNA-binding domain: a possible role for
conformational instability of the protein in DNA binding and control of gene
expression.
AB - Double- and triple-resonance heteronuclear NMR spectroscopy have been used to
determine the high-resolution solution structure of the minimal B-Myb DNA-binding
domain (B-MybR2R3) and to characterize the specific complex formed with a
synthetic DNA fragment corresponding to the Myb target site on the Myb-regulated
gene tom-1. B-MybR2R3 is shown to consist of two independent protein domains (R2
and R3) joined by a short linker, which have strikingly different tertiary
structures despite significant sequence similarities. In addition, the C-terminal
region of B-Myb R2 is confirmed to have a poorly defined structure, reflecting
the existence of multiple conformations in slow to intermediate exchange. This
contrasts with the tertiary structure reported for c-MybR2R3, in which both R2
and R3 have the same fold and the C-terminal region of R2 forms a stable, well
defined helix [Ogata, K., et al. (1995) Nat. Struct. Biol. 2, 309-320]. The NMR
data suggest there are extensive contacts between B-MybR2R3 and its DNA target
site in the complex and are consistent with a significant conformational change
in the protein on binding to DNA, with one possibility being the formation of a
stable helix in the C-terminal region of R2. In addition, conformational
heterogeneity identified in R2 of B-MybR2R3 bound to the tom-1-A target site may
play an important role in the control of gene expression by Myb proteins.
PMID- 9657675
TI - Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of
human immunodeficiency virus type-1 reverse transcriptase is compensated by Met
to Val substitution within the same motif.
AB - Tyr183 is a constituent of the highly conserved YXDD motif common to all
retroviral reverse transcriptases. The two aspartates in this motif are the
crucial members of the catalytic carboxylate triad while residue X, which in the
case of HIV-1 RT is Met184, is implicated in dNTP substrate recognition and
fidelity of DNA synthesis. In an attempt to understand the function of Tyr183 in
the catalytic mechanism, we generated mutants of this residue (Y183F and Y183A)
and subjected them to in-depth analysis. The efficiency of reverse transcription
of natural U5-PBS HIV-1 RNA template was severely impaired by both the
conservative and nonconservative substitutions. The major defect identified was
at the level of dNTP binding as determined by a 20-80-fold increase in the Km for
the dNTP substrate on both homopolymeric and heteropolymeric RNA and DNA
templates. A significant reduction in processivity of DNA synthesis by these
mutants was also noted. However, the fidelity of DNA synthesis by the Y183F and
Y183A mutants was increased significantly compared to the wild-type enzyme.
Interestingly, the reduction in the polymerase activity due to single
substitution of Tyr to Phe in the YMDD motif is compensated by a second
substitution of Met to Val in the same motif, herein referred to as the FVDD. The
loss of dNTP binding as well as decreased processivity of DNA synthesis exhibited
by the Y183F mutant was also compensated by mutation at the second site.
Curiously, the double mutant did not exhibit any synergistic effect in regard to
fidelity of DNA synthesis as might be expected since both the single mutations
(Y183F, M184V) exhibited enhanced fidelity compared to the wild-type enzyme.
These data implicate Tyr183 and Met184 as important constituents of the dNTP
binding pocket. We propose a model which suggests that subtle structural changes
due to mutation in the flexible beta9-beta10 loop region at the active site of
the molecule influence the enzyme activity and substrate recognition.
PMID- 9657676
TI - Solution structure of thermostable cytochrome c-552 from Hydrogenobacter
thermophilus determined by 1H-NMR spectroscopy.
AB - The solution structure of a thermostable cytochrome c-552 from a thermophilic
hydrogen oxidizing bacterium Hydrogenobacter thermophilus was determined by
proton nuclear magnetic resonance spectroscopy. Twenty structures were calculated
by the X-PLOR program on the basis of 902 interproton distances, 21 hydrogen
bonds, and 13 torsion angle constraints. The pairwise average root-mean-square
deviation for the main chain heavy atoms was 0.91 +/- 0.11 A. The main chain
folding of the cytochrome c-552 was almost the same as that of Pseudomonas
aeruginosa cytochrome c-551 that has 59% sequence identity to the cytochrome c
552 but is less thermostable. We found several differences in local structures
between the cytochromes c-552 and c-551. In the cytochrome c-552, aromatic-amino
interactions were uniquely formed between Arg 35 and Tyr 32 and/or Tyr 41, the
latter also having hydrophobic contacts with the side chains of Tyr 32, Ala 38,
and Leu 42. Small hydrophobic cores were more tightly packed in the cytochrome c
552 because of the occupancies of Ala 5, Met 11, and Ile 76, each substituted by
Phe 7, Val 13, and Val 78, respectively, in the cytochrome c-551. Some of these
structural differences may contribute to the higher thermostability of the
cytochrome c-552.
PMID- 9657677
TI - TIMP-1 contact sites and perturbations of stromelysin 1 mapped by NMR and a
paramagnetic surface probe.
AB - Surfaces of the 173 residue catalytic domain of human matrix metalloproteinase 3
(MMP-3(DeltaC)) affected by binding of the N-terminal, 126 residue inhibitory
domain of human TIMP-1 (N-TIMP-1) have been investigated using an amide-directed,
NMR-based approach. The interface was mapped by a novel method that compares
amide proton line broadening by paramagnetic Gd-EDTA in the presence and absence
of the binding partner. The results are consistent with the X-ray model of the
complex of MMP-3(DeltaC) with TIMP-1 (Gomis-Ruth et al. (1997) Nature 389, 77
81). Residues Tyr155, Asn162, Val163, Leu164, His166, Ala167, Ala169, and Phe210
of MMP-3(DeltaC) are protected from broadening by the Gd-EDTA probe by binding to
N-TIMP-1. N-TIMP-1-induced exposure of backbone amides of Asp238, Asn240, Gly241,
and Ser244 of helix C of MMP-3(DeltaC) to Gd-EDTA confirms that the displacement
of the N-terminus of MMP-3(DeltaC) occurs not only in the crystal but also in
solution. These results validate comparative paramagnetic surface probing as a
means of mapping protein-protein interfaces. Novel N-TIMP-1-dependent changes in
hydrogen bonding near the active site of MMP-3(DeltaC) are reported. N-TIMP-1
binding causes the amide of Tyr223 of MMP-3(DeltaC) bound by N-TIMP-1 to exchange
with water rapidly, implying a lack of the hydrogen bond observed in the crystal
structure. The backbone amide proton of Asn162 becomes protected from rapid
exchange upon forming a complex with N-TIMP-1 and could form a hydrogen bond to N
TIMP-1. N-TIMP-1 binding dramatically increases the rate of amide hydrogen
exchange of Asp177 of the fifth beta strand of MMP-3(DeltaC), disrupting its
otherwise stable hydrogen bond.
PMID- 9657678
TI - Identification of a residue involved in transition-state stabilization in the
ATPase reaction of DNA gyrase.
AB - Examination of the X-ray crystal structure of the 43 kDa N-terminal domain of the
DNA gyrase B protein (GyrB) shows that the majority of the interactions with
bound ATP are made with subdomain 1 (residues 2-220). However, two residues from
subdomain 2, Gln335 and Lys337, interact with the gamma-phosphate of ATP. The
proposed roles for these residues include nucleotide binding, transition-state
stabilization, and triggering protein conformational changes. We have used site
directed mutagenesis to convert Gln335 to Asn and Ala and Lys337 to Gln and Ala
in the N-terminal domain of GyrB. Two of the resultant mutant proteins,
GyrB43(Q335A) and GyrB43(K337Q), were shown to be correctly folded, and their
interactions with ATP have been analyzed in detail. The Q335A protein is
apparently unchanged with regard to nucleotide binding and hydrolysis, whereas
the K337Q protein shows a modest decrease in nucleotide binding and a drastic
reduction in ATPase activity. This is manifested by a approximately 10(3)-fold
decrease in kcat. When the two mutations were moved into full-length GyrB, the
Q335A mutation again showed little or no effect on activity, whereas the K337Q
mutation had undetectable supercoiling and ATPase activities. We conclude that
Gln335 is dispensable for ATP binding and hydrolysis by the gyrase B protein,
whereas Lys337 has a critical role in the ATPase reaction and is likely to be a
key residue in transition-state stabilization.
PMID- 9657679
TI - Role of methionine 56 in the control of the oxidation-reduction potentials of the
Clostridium beijerinckii flavodoxin: effects of substitutions by aliphatic amino
acids and evidence for a role of sulfur-flavin interactions.
AB - Flavodoxins are small electron transferases that participate in low-potential
electron transfer pathways. The flavodoxin protein is able to separate the two
redox couples of the noncovalently bound flavin mononucleotide (FMN) cofactor
through the differential thermodynamic stabilization or destabilization of each
of its redox states. In the flavodoxin from Clostridium beijerinckii, the sulfur
atom of methionine 56 is in direct contact with the re or inner face of the
isoalloxazine ring of the FMN cofactor. In this study, evidence was sought for a
possible role for sulfur-aromatic (flavin) interactions in the regulation of one
electron reduction potentials in flavoproteins. Met56 was systematically replaced
with all the naturally occurring aliphatic amino acids by site-directed
mutagenesis. Replacement of Met56 with alanine or glycine increased the midpoint
potentials at pH 7 for the oxidized-semiquinone couple by up to 20 mV compared to
that of the wild type, while replacement by the longer chain aliphatic residues
decreased the midpoint potential by >30 mV. The midpoint potential for the
semiquinone-hydroquinone couple was less negative than that for the wild type for
all the mutants, increasing by as much as 90 mV for the M56I mutant. For the M56A
mutant, the loss of approximately 0.5 kcal/mol in the binding energy for oxidized
FMN and an increase of 1. 6 kcal/mol for the flavin hydroquinone, relative to
that of the wild type, are responsible for the observed changes in the midpoint
potentials. The stability of the semiquinone complex of this mutant was not
affected. The one-election reduction potentials for the M56L, M56I, and M56V
mutants are also influenced by the differential stabilization of the three redox
states; however, the semiquinone complex was significantly less stable in these
proteins. These differences are likely the consequence of the introduction of
additional steric factors and an apparent structural preference for a smaller or
more flexible side chain at this position in the semiquinone complex. While the
other factors may contribute, it is argued that the results obtained for the
entire group of mutants are consistent with the elimination of important sulfur
flavin interactions that contribute in part to the stabilization of the oxidized
and destabilization of the hydroquinone states of the cofactor in this
flavodoxin. The results of this study also demonstrate unequivocally the
functional importance of this methionine residue and that it is unique among the
aliphatic amino acids in its capacity to generate the physiologically relevant
low reduction potential exhibited by the C. beijerinckii flavodoxin.
PMID- 9657681
TI - Temperature-controlled activity of DnaK-DnaJ-GrpE chaperones: protein-folding
arrest and recovery during and after heat shock depends on the substrate protein
and the GrpE concentration.
AB - Heat-shock proteins DnaK, DnaJ, and GrpE (KJE) from Escherichia coli constitute a
three-component chaperone system that prevents aggregation of denatured proteins
and assists the refolding of proteins in an ATP-dependent manner. We found that
the rate of KJE-mediated refolding of heat- and chemically denatured proteins is
decreased at high temperatures. The efficiency and reversibility of protein
folding arrest during and after heat shock depended on the stability of the
complex between KJE and the denatured proteins. Whereas a thermostable protein
was released and partially refolded during heat shock, a thermolabile protein
remained bound to the chaperone. The apparent affinity of GrpE and DnaJ for DnaK
was decreased at high temperatures, thereby decreasing futile consumption of ATP
during folding arrest. The coupling of ATP hydrolysis and protein folding was
restored after the stress. This strongly indicates that KJE chaperones are heat
regulated heat-shock proteins which can specifically arrest the folding of
aggregation-prone proteins during stress and preferentially resume refolding
under conditions that allow individual proteins to reach and maintain a stable
native conformation.
PMID- 9657680
TI - Kinetic characterization of myosin head fragments with long-lived myosin.ATP
states.
AB - We have separately expressed the Dictyosteliumdiscoideum myosin II nonhydrolyzer
point mutations E459V and E476K [Ruppel, K. M., and Spudich, J. A. (1996) Mol.
Biol. Cell 7, 1123-1136] in the soluble myosin head fragment M761-1R [Anson et
al. (1996) EMBO J. 15, 6069-6074] and performed transient kinetic analyses to
characterize the ATPase cycles of the mutant proteins. While the mutations cause
some changes in mantATP [2'(3')-O-(N-methylanthraniloyl)-ATP] and mantADP
binding, the most dramatic effect is on the hydrolysis step of the ATPase cycle,
which is reduced by 4 (E476K) and 6 (E459V) orders of magnitude. Thus, both
mutant myosin constructs do in fact catalyze ATP hydrolysis but have very long
lived myosin.ATP states. The E459V mutation allowed for a direct measurement of
the ATP off rate constant from myosin, which was found to be 2 x 10(-)5 s-1.
Actin accelerated ATP release from this E459V construct by at least 100-fold.
Additionally, we found that the affinity of the E476K construct for actin is
significantly weaker than for the wild-type construct, while the E459V mutant
interacts with actin normally. Their functional properties and the fact that they
can be produced and purified in large amounts make the E476K and E459V constructs
ideal tools to elucidate key structural features of the myosin ATPase cycle.
These constructs should allow us to address important questions, including how
binding of ATP to myosin heads results in a >3 order of magnitude reduction in
actin affinity.
PMID- 9657682
TI - Engineering steroid 5 beta-reductase activity into rat liver 3 alpha
hydroxysteroid dehydrogenase.
AB - Delta 4-3-Ketosteroid-5 beta-reductase (5 beta-reductase) precedes 3 alpha
hydroxysteroid dehydrogenase (3 alpha-HSD) in steroid hormone metabolism. Both
enzymes are members of the aldo-keto reductase (AKR) superfamily and possess
catalytic tetrads differing by a single amino acid. In 3 alpha-HSD, the tetrad
consists of Tyr55, Lys84, Asp50, and His117, but a glutamic acid replaces His117
in 5 beta-reductase. By introducing the H117E point mutation into 3 alpha-HSD, we
engineered 5 beta-reductase activity into the dehydrogenase. Homogeneous H117E 3
alpha-HSD reduced the double bond in testosterone to form 5 beta
dihydrotestosterone with kcat = 0.25 min-1 and Km = 19.0 microM and reduced the
double bond in progesterone to generate 5 beta-dihydroprogesterone with kcat =
0.97 min-1 and Km = 33.0 microM. These kinetic parameters were similar to those
reported for homogeneous rat liver 5 beta-reductase [Okuda, A., and Okuda, R.
(1984) J. Biol. Chem. 259, 7519-7524]. The H117E mutant also reduced 5beta
dihydrosteroids to 5 beta, 3 alpha-tetrahydrosteroids with a 600-1000-fold
decrease in kcat/Km versus wild-type 3 alpha-HSD. The ratio of 5 beta-reductase:3
alpha-HSD activity in the H117E mutant was approximately 1:1. Although the H117A
mutant reduced Delta 4-3-ketosteroids, the 3 alpha-HSD activity predominated
because the 5 beta-dihydrosteroids were rapidly converted to the 5 beta,3 alpha
tetrahydrosteroids. The pH-rate profiles for carbon-carbon double-bond and ketone
reduction catalyzed by the H117E mutant were superimposable, suggesting a common
titratable group (pKb = 6.3) for both reactions. In wild-type 3 alpha-HSD, the
titratable group responsible for 3-ketosteroid reduction has a pKb = 6.9 and is
assignable to Tyr55. The pH-rate profiles for 3-ketosteroid reduction by the
H117A mutant were pH-independent. Our data indicate that Tyr55 functions as a
general acid for both 3 alpha-HSD and 5 beta-reductase activities. We suggest
that a protonated Glu117 increases the acidity of Tyr55 to promote acid-catalyzed
enolization of the Delta 4-3-ketosteroid substrate. Further, the identity of
amino acid 117 determines whether an AKR can function as a 5 beta-reductase by
reorienting the substrate relative to the nicotinamide cofactor. This study
provides functional evidence that utilization of modified catalytic residues on
an identical protein scaffold is important for evolution of enzymatic activities
within the same metabolic pathway.
PMID- 9657683
TI - Structural and enzymatic studies of a new analogue of coenzyme B12 with an alpha
adenosyl upper axial ligand.
AB - A new analogue of coenzyme B12 (5'-deoxyadenosylcobalamin, AdoCbl), in which the
configuration of the N-glycosidic bond in the Ado ligand is inverted [(alpha
ribo)AdoCbl], has been synthesized and its crystal structure determined by X-ray
diffraction [MoKalpha, lambda = 0.71073 A, monoclinic P212121, a = 16.132(12) A,
b = 21. 684(15) A, c = 27.30(3) A, 9611 independent reflections, R1 = 0. 0708].
As suggested by molecular mechanics modeling before the structure was known, the
Ado ligand lies over the southern quadrant of the molecule, as is the case for
AdoCbl. The most striking feature of the structure is disorder in the orientation
of the adenine (Ade) moiety relative to the ribose of the Ado ligand. This was
resolved with a two-state model in which in the major (0.57 occupancy) conformer
the A16(O)-A11-A9(N)-A8 dihedral angle is 1.9 degrees and the Ade is virtually
perpendicular to the corrin ring; in the minor conformer, the Ade is tilted down,
and this dihedral is -48.7 degrees. The Co-C and axial Co-N bond lengths and the
Co-C-C bond angle are quite similar to those in AdoCbl. The corrin ring is
considerably flatter than that of AdoCbl, with a fold angle of 11.7 degrees. The
molecule was successfully modeled by molecular mechanics (MM), and rotation of
the Ado ligand relative to the corrin gave rise to four locally minimum
structures with the Ado in the southern, eastern, northern, or western quadrant,
with the southern conformation as the global minimum, as is the case with AdoCbl
itself. Nuclear Overhauser effects (nOe's) observed by two-dimensional (2D) NMR
were incorporated as restraints in molecular dynamics (MD) and simulated
annealing (SA) calculations. A MD simulation at 300 K showed that only the
southern conformation is populated with the Ado ligand confined to an arc from
over C15 to over C12, while the Ade ring oscillates from perpendicular to
parallel to the corrin ring. Twenty-seven structures were collected by MD-SA.
Most of these annealed into the southern conformation, but examples of the other
conformations were also found. The new analogue is a partially active coenzyme
for the ribonucleotide reductase from Lactobacillus leichmanii with maximal
activity that is 9.7% of that of AdoCbl itself, and a very high Km value (245
microM compared to 0.54 microM for AdoCbl). In addition, the rate constant for
enzyme-induced carbon-cobalt bond cleavage of (alpha-ribo)AdoCbl is 160-fold
smaller than that for AdoCbl, and only 1/3 as much cob(II)alamin is produced at
the active site.
PMID- 9657684
TI - Proposed steady-state kinetic mechanism for Corynebacterium ammoniagenes FAD
synthetase produced by Escherichia coli.
AB - The bifunctional enzyme, FAD synthetase (FS), from Corynebacterium ammoniagenes
was overproduced in Escherichia coli and purified, and its steady-state kinetic
properties were investigated. Although FMN is an intermediate product in the
conversion of riboflavin to FAD, FMN must be released after formation, and then
rebind for adenylylation. It was shown that adenylylation of FMN is reversible;
FAD and pyrophosphate can be converted to FMN and ATP by the enzyme. In contrast,
under the conditions studied, phosphorylation of riboflavin is irreversible. A
method is described for analysis of two catalytic cycles, occurring on one
enzyme, which have a substrate and/or product in common. The binding order for
the phosphorylation cycle of FS was established as riboflavin(in), ATP(in),
ADP(out), and FMN(out). The order for the adenylylation cycle was ATP(in),
FMN(in), pyrophosphate(out), and FAD(out). A set of steady-state constants was
determined, and without additional optimization, these constants were sufficient
to describe experimental progress curves for conversion of riboflavin to FAD. In
independent studies, it was demonstrated that FMN binds to apo-FS with a
dissociation constant of 6-7 microM, which is 2 orders of magnitude higher than
the KD value for riboflavin. For the steady-state kinetic analysis, this
represents reversible binding of FMN(out) in the phosphorylation cycle (cycle I),
which effectively inhibits catalysis in the adenylylation cycle (cycle II).
PMID- 9657686
TI - High-efficiency incorporation in vivo of tyrosine analogues with altered hydroxyl
acidity in place of the catalytic tyrosine-14 of Delta 5-3-ketosteroid isomerase
of Comamonas (Pseudomonas) testosteroni: effects of the modifications on
isomerase kinetics.
AB - Versions of the Y55F/Y88F modified form of Delta 5-3-ketosteroid isomerase in
which the active-site tyrosine-14 is replaced by 2-fluorotyrosine, 3
fluorotyrosine, and 2,3-difluorotyrosine, amino acids having progressively
greater acidity of their phenolic hydroxyls, have been expressed in an
Escherichia coli host and purified to high homogeneity. The steady-state kinetic
properties of Y55F/Y88F KSI and its fluorotyrosine modified forms have been
determined. The mechanistic implications of the results are presented and
discussed.
PMID- 9657685
TI - Effects of changes in three catalytic residues on the relative stabilities of
some of the intermediates and transition states in the citrate synthase reaction.
AB - This work reports the relative importance of the interactions provided by three
catalytic residues to individual steps in the mechanism of citrate synthase. When
the side chains of any of the residues (H320, D375, and H274) are mutated, the
data indicate that they are involved in the stabilization of one or more of the
transition/intermediate states in the multistep citrate synthase reaction. H320
forms a hydrogen bond with the carbonyl of oxaloacetate and the alcohols of the
citryl-coenzyme A and citrate products. Enzymes substituted at H320 (Q, G, N, and
R) have reaction profiles for which the condensation reaction is cleanly rate
determining. None of these mutants can activate the carbonyl of oxaloacetate by
polarization. All these mutants catalyze the necessary proton transfer from the
methyl group of acetyl-coenzyme A only poorly, a process which occurs in a
structurally separate site. Furthermore, all H320 mutants hydrolyze the citryl
coenzyme A intermediate significantly more slowly than does the wild-type. D375
is the base removing the proton of acetyl-coenzyme A. D375E and D375G have
greatly diminished ability to catalyze proton transfer from acetyl-CoA. The D375
mutants polarize the oxaloacetate carbonyl as well as wild-type. For D375E, the
hydrolysis of citryl-CoA is rate determining. D375G, having no side chain capable
of acid-base chemistry in either the condensation or hydrolysis reactions is
nearly completely devoid of activity in any of the reactions catalyzed by the
wild-type. H274 hydrogen bonds to the carbonyl of acetyl-coenzyme A but also
forms the back wall of the oxaloacetate-binding site. H274G cannot properly
activate either oxaloacetate or acetyl-coenzyme A, and the condensation reaction
is overwhelmingly rate determining. Nonetheless, hydrolysis of the intermediate
is impaired. All the enzymes except H320R and H274G show kinetic cooperativity
with CitCoA as substrate, indicating changes in the subunit interactions with
these latter two mutants. The energetics of citrate synthase are surprisingly
tightly coupled. All changes affect more than one step in the catalytic cycle.
Within the condensation reaction, the intermediate of proton transfer must occupy
a shallow well between transition states close in free energy so that
perturbations of one have substantial effects on that of the other.
PMID- 9657687
TI - Reaction paths of iron oxidation and hydrolysis in horse spleen and recombinant
human ferritins.
AB - UV-visible spectroscopy, electrode oximetry, and pH stat were used to study
Fe(II) oxidation and hydrolysis in horse spleen ferritin (HoSF) and recombinant
human H-chain and L-chain ferritins (HuHF and HuLF). Appropriate test reactions
and electrode responses were measured, establishing the reliability of oxygen
electrode/pH stat for kinetics studies of iron uptake by ferritin. Stoichiometric
ratios, Fe(II)/O2 and H+/Fe(II), and rates of oxygen uptake and proton production
were simultaneously measured as a function of iron loading of the protein. The
data show a clear distinction between the diiron ferroxidase site and mineral
surface catalyzed oxidation of Fe(II). The oxidation/hydrolysis reaction
attributed to the ferroxidase site has been determined for the first time and is
given by 2Fe2+ + O2 + 3H2O --> [Fe2O(OH)2]2+ + H2O2 + 2H+ where [Fe2O(OH)2]2+
represents the hydrolyzed dinuclear iron(III) center postulated to be a mu-oxo
bridged species from UV spectrometric titration data and absorption band maxima.
The transfer of iron from the ferroxidase site to the mineral core has been now
established to be [Fe2O(OH)2]2+ + H2O --> 2FeOOH(core) + 2H+. Regeneration of
protein ferroxidase activity with time is observed for both HoSF and HuHF,
consistent with their having enzymatic properties, and is facilitated by higher
pH (7.0) and temperature (37 degreesC) and by the presence of L-subunit and is
complete within 10 min. In accord with previous studies, the mineral surface
reaction is given by 4Fe2+ + O2 + 6H2O --> 4FeOOH(core) + 8H+. As the protein
progressively acquires iron, oxidation/hydrolysis increasingly shifts from a
ferroxidase site to a mineral surface based mechanism, decreasing the production
of H2O2.
PMID- 9657688
TI - Q-band resonance Raman spectra of oxidized and reduced mitochondrial bc1
complexes.
AB - Recently published crystallographic studies of mitochondrial bc1 complexes have
stimulated renewed interest in the active site architecture of these important
integral membrane proteins. We present resonance Raman spectra obtained via
variable excitation within the heme Q-band from samples poised in several
different net redox states. Appropriate subtraction and polarization analysis
allows the vibrational behavior of the individual heme bL,bH, and c1 sites to be
assessed. The spectra of the b hemes are particularly noteworthy. They exhibit
evidence for a protonation equilibrium involving heme axial ligands and reveal a
marked structural heterogeneity at the heme bH site that most likely involves
nonplanar distortions of the macrocycle. The possible implications of these
findings for heme functionality are discussed.
PMID- 9657689
TI - The PsaE subunit is required for complex formation between photosystem I and
flavodoxin from the cyanobacterium Synechocystis sp. PCC 6803.
AB - The photoreduction of the oxidized and the semiquinone form of flavodoxin by
photosystem I particles (PSI) from the wild type and a psaE deletion strain from
the cyanobacterium Synechocystis sp. PCC 6803 was analyzed by flash-absorption
spectroscopy to investigate a possible involvement of the PsaE subunit in this
photoreduction process. The kinetics of the reduction of oxidized flavodoxin
display a single-exponential component for both PSI preparations. Limiting
electron transfer rates kobs of approximately 500 and approximately 900 s -1 are
deduced for the wild type and PSI from the psaE-less mutant, respectively,
indicating that the PsaE subunit is not important for this photoreduction
process. In the case of wild-type PSI, the reduction of flavodoxin semiquinone is
a biphasic process, displaying a fast first-order phase with a t1/2 of
approximately 13 micro(s) which is then followed by a slower, concentration
dependent phase, for which a second-order rate constant k2 of 2.2 x 10(8) M-1 cm
1 is calculated. In contrast, photoreduction of the semiquinone by PSI from the
psaE-less mutant is monoexponential, displaying only one second-order component
with a second-order rate constant similar to those observed for wild-type PSI (k2
= 1.5 x 10(8) M-1 cm-1). The fast first-order component which is interpreted as
an electron transfer process within a preformed complex between flavodoxin
semiquinone and PSI is almost completely absent in the reduction of flavodoxin by
the PsaE-less PSI. A similar loss of the fast phase is also observed for the
photoreduction of flavodoxin semiquinone by PSI from a Synechococcus elongatus
psaE-less mutant. Upon reconstitution of isolated PsaE to the PsaE-less PSI in
vitro, approximately 80% of the fast first-order kinetic component is recovered,
indicating that PsaE is required for high-affinity binding of the flavodoxin
semiquinone to PSI. In addition, chemical cross-linking assays show that
flavodoxin can no longer be cross-linked to PSI in detectable amounts when PsaE
is missing on the reaction center. Taken together, these experiments indicate
that the PsaE subunit is required for complex formation between PSI and
flavodoxin but is not required for an efficient forward electron transfer from
photosystem I to both forms of flavodoxin.
PMID- 9657690
TI - Incorrect folding of steroidogenic acute regulatory protein (StAR) in congenital
lipoid adrenal hyperplasia.
AB - Steroidogenic acute regulatory protein (StAR) rapidly stimulates the movement of
cholesterol into adrenal and gonadal mitochondria to mediate the acute
steroidogenic response; StAR mutations cause potentially lethal congenital lipoid
adrenal hyperplasia (lipoid CAH). Bacterially expressed wild-type StAR and four
amino acid replacement/deletion mutants that cause lipoid CAH were purified to
apparent homogeneity. Sedimentation equilibrium ultracentrifugation showed that
all five proteins were monomeric and fit a globular protein model of the correct
molecular mass. Circular dichroism (CD) spectra of both the wild-type and mutants
showed minima near 208 and 222 nm, confirming the presence of substantial alpha
helical structure. However, subtle differences in the CD signals of the wild-type
and mutants in the far-UV and stronger differences in near-UV indicated
differences in protein folding. The amide I and II bands in the 1400-1700 cm-1
region of Fourier transform infrared spectra showed that the proteins fell into
two groups. The wild-type and a partially active conservative mutant were
predominantly alpha-helical with some intramolecular beta-sheet. By contrast,
three mutants that lost charged residues retained much of their alpha-helical
structure, but also tended to form intermolecular beta-sheets. Urea at 2.0 or 4.0
M had less effect on the CD spectrum of the wild-type than of the mutants,
particularly those having lost a charged residue; 50 mM guanidinium hydrochloride
did not alter the CD spectrum of the wild-type, but elicited dramatic changes to
the secondary structure in all four mutants. Despite this, thermal melting curves
of the mutant proteins in 50 mM guanidinium hydrochloride showed surprising
stability, even exceeding that of the wild-type protein. These data suggest that
the StAR amino acid replacement mutants that cause lipoid CAH are inactive
because of fairly gross errors in protein folding, probably due to the loss of
salt bridges that stabilize the tertiary structure.
PMID- 9657691
TI - Phosphatidylinositol 3,4,5-trisphosphate triggers platelet aggregation by
activating Ca2+ influx.
AB - Exogenous phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] stimulates
the aggregation of washed rabbit platelets in a Ca2+- and dose-dependent manner.
This aggregation is reversible at low PtdIns(3,4,5)P3 levels, but becomes
irreversible when the concentration exceeds a threshold of about 20 microM. Other
D-3 and D-4 phosphoinositides examined, including phosphatidylinositol 3, 4
bisphosphate [PtdIns(3,4)P2], phosphatidylinositol 4, 5-bisphosphate
[PtdIns(4,5)P2], and phosphatidylinositol 3-monophosphate [PtdIns(3)P], fail to
exert appreciable platelet activation at comparable concentrations. In addition,
PtdIns(3,4, 5)P3 can reverse the inhibitory effect of wortmannin on thrombin
induced platelet aggregation. Taken together with the observation that
PtdIns(3,4,5)P3 is readily incorporated into cell membranes, these findings
reaffirm the second messenger role of PtdIns(3,4,5)P3 in thrombin receptor
activation. The existence of a PtdIns(3,4,5)P3-dependent Ca2+ entry system on
platelet membranes is supported by the partial inhibition of thrombin-induced
Ca2+ influx by wortmannin. Evidence suggests that this system differs from
receptor-operated nonselective Ca2+ channels. However, the mechanism by which
PtdIns(3,4,5)P3 facilitates Ca2+ entry remains unclear. Although PtdIns(3,4,5)P3
has been known to stimulate phospholipase C-gamma (PLC-gamma), internal Ca2+
mobilization does not play a significant role in the cytosolic Ca2+ increase in
response to PtdIns(3,4,5)P3 stimulation. Collectively, these data provide a
putative link between PtdIns(3,4,5)P3 and Ca2+ signaling, which may, in part,
account for the regulatory function of PtdIns(3,4,5)P3 during platelet
aggregation. Moreover, this study bears out the notion that individual PI 3
kinase lipid products play distinct roles in the regulation of cellular
functions.
PMID- 9657692
TI - Core domain mutation (S86Y) selectively inactivates polyubiquitin chain synthesis
catalyzed by E2-25K.
AB - The mammalian ubiquitin conjugating enzyme known as E2-25K catalyzes the
synthesis of polyubiquitin chains linked exclusively through K48-G76 isopeptide
bonds. The properties of truncated and chimeric forms of E2-25K suggest that the
polyubiquitin chain synthesis activity of this E2 depends on specific
interactions between its conserved 150-residue core domain and its unique 50
residue tail domain [Haldeman, M. T., Xia, G., Kasperek, E. M., and Pickart, C.
M. (1997) Biochemistry 36, 10526-10537]. In the present study, we provide strong
support for this model by showing that a point mutation in the core domain (S86Y)
mimics the effect of deleting the entire tail domain: the ability to form an E2
approximately ubiquitin thiol ester is intact, while conjugation activity is
severely inhibited (>/=100-fold reduction in kcat/Km). The properties of E2-25K
enzymes carrying the S86Y mutation indicate that this mutation strengthens the
interaction between the core and tail domains: both free and ubiquitin-bound
forms of S86Y-25K are completely resistant to tryptic cleavage at K164 in the
tail domain, whereas wild-type enzyme is rapidly cleaved at this site. Other
properties of S86Y-26K suggest that the active site of this mutant enzyme is more
occluded than the active site of the wild-type enzyme. (1) Free S86Y-25K is
alkylated by iodoacetamide 2-fold more slowly than the wild-type enzyme. (2) In
assays of E2 approximately ubiquitin thiol ester formation, S86Y-25K shows a 4
fold reduced affinity for E1. (3) The ubiquitin thiol ester adduct of S86Y-25K
undergoes (uncatalyzed) reaction with dithiothreitol 3-fold more slowly than the
wild-type thiol ester adduct. One model to accommodate these findings postulates
that an enhanced interaction between the core and tail domains, induced by the
S86Y mutation, causes a steric blockade at the active site which prevents access
of the incoming ubiquitin acceptor to the thiol ester bond. Consistent with this
model, the S86Y mutation inhibits ubiquitin transfer to macromolecular acceptors
(ubiquitin and polylysine) more strongly than transfer to small-molecule
acceptors (free lysine and short peptides). These results suggest that unique
residues proximal to E2 active sites may influence specific function by mediating
intramolecular interactions.
PMID- 9657693
TI - Human cytomegalovirus protease complexes its substrate recognition sequences in
an extended peptide conformation.
AB - Substrate hydrolysis by human cytomegalovirus (HCMV) protease is essential to
viral capsid assembly. The interaction of HCMV protease and the N-terminal
cleavage products of the hydrolysis of R- and M-site oligopeptide substrate
mimics (R and M, respectively, which span the P9-P1 positions) was studied by NMR
methods. Protease-induced differential line broadening indicated that ligand
binding is mediated by the P4-P1 amino acid residues of the peptides. A well
defined extended conformation of R from P1 through P4 when complexed to HCMV
protease was evidenced by numerous transferred nuclear Overhauser effect (NOE)
correlations for the peptide upon addition of the enzyme. NOE cross-peaks between
the P4 and P5 side chains placing these two groups in proximity indicated a
deviation from the extended conformation starting at P5. Similar studies carried
out for the M peptide also indicated an extended peptide structure very similar
to that of R, although the conformation of the P5 glycine could not be
established. No obvious variation in structure between bound R and M (notably at
P4, where the tyrosine of the R-site has been suggested to play a key role in
ligand binding) could be discerned that might explain the observed differences in
processing rates between R- and M-sequences. Kinetic studies, utilizing R- and M
site peptide substrates for which the P5 and P4 residues were separately
exchanged, revealed that these positions had essentially no influence on the
specificity constants (kcat/KM). In sharp contrast, substitution of the P2
residue of an M-site peptide changed its specificity constant to that of an R
site peptide substrate, and vice versa.
PMID- 9657694
TI - Quantitative hydroxyl radical footprinting reveals cooperative interactions
between DNA-binding subdomains of PU.1 and IRF4.
AB - Quantitative hydroxyl radical footprinting and fluorescence polarization
measurements have been used to determine the dissociation constants (Kd) of
complexes between the ets domain of the murine transcription factor PU.1 and
three different DNA fragments. Two natural PU.1 binding sites, the SV40 enhancer
site and the lambdaB motif of Iglambda2-4 enhancer, were used as well as the PU.1
binding site present in the crystallized PU.1-DNA complex. With the use of
quantitative hydroxyl radical footprinting we obtained binding isotherms for
individual protected nucleotides and contact sites on both strands of the DNA. Kd
values of (1.53 +/- 0. 12) x 10(-)8 M were found for the lambdaB element, (3.60
+/- 0.65) x 10(-)8 M for the SV40 enhancer site, and (2.28 +/- 0.27) x 10(-)8 M
for the sequence used in the crystal structure. In addition, the binding of a
second protein, the DNA binding domain of IRF4, to the lambdaB site by itself and
in the presence of PU.1 was analyzed. The IRF4 DBD shows three footprints on the
TTCC strand and one footprint on the GGAA strand of the lambdaB element. The
dissociation constant for the binary IRF4 DBD-lambdaB complex equals (5.59 +/-
0.60) x 10(-)7 M. The Kd value of the IRF4-lambdaB interaction is reduced by a
factor of 5 in the presence of two different DNA-bound PU.1 protein constructs,
PU.1 DBD and a PU.1 construct containing the PEST domain (PU.1-PEST). A similar
decrease of the Kd value was observed for the binding of PU.1-PEST in the
presence of DNA-bound IRF4 DBD demonstrating a cooperative interaction between
the PU. 1-PEST and IRF4 DBD. On the basis of the hydroxyl radical footprints in
the ternary PU.1/IRF4/lambdaB complex, a model for the interactions between the
two proteins and the lambdaB site was developed. The DNA binding domains of both
proteins bind the DNA in the major groove with potential protein-protein
interactions near the intervening minor groove.
PMID- 9657695
TI - Solution structure of the oxidized Fe7S8 ferredoxin from the thermophilic
bacterium Bacillus schlegelii by 1H NMR spectroscopy.
AB - The solution structure of the paramagnetic seven-iron ferredoxin from Bacillus
schlegelii in its oxidized form has been determined by 1H NMR. The protein, which
contains 77 amino acids, is thermostable. Seventy-two residues and 79% of all
theoretically expected proton resonances have been assigned. The structure has
been determined through torsion angle dynamics calculations with the program
DYANA, using 966 meaningful NOEs (from a total of 1305), hydrogen bond
constraints, and NMR derived dihedral angle constraints for the cluster ligating
cysteines, and by using crystallographic information to build up the two
clusters. Afterwards, restrained energy minimization and restrained molecular
dynamics were applied to each conformer of the family. The final family of 20
structures has RMSD values from the mean structure of 0.68 A for the backbone
atoms and of 1.16 A for all heavy atoms. The contributions to the thermal
stability of the B. schlegelii ferredoxin are discussed by comparing the present
structure to that of the less stable Azotobacter vinelandii ferredoxin I which is
the only other available structure of a bacterial seven-iron ferredoxin. It is
proposed that the hydrophobic interactions and the hydrogen bond network linking
the N-terminus and the C-terminus together and a high number of salt bridges
contribute to the stability.
PMID- 9657696
TI - Implication of DNA-dependent protein kinase in an early, essential, local
phosphorylation event during end-joining of DNA double-strand breaks in vitro.
AB - Previous work with Xenopus egg extracts suggested that a wortmannin-sensitive
protein phosphorylation event precedes both the removal of modified termini from
DNA double-strand break ends and the joining of unmodified ends. To assess the
possible role of DNA-dependent protein kinase in effecting this phosphorylation,
both DNA end-joining and DNA-stimulated phosphorylation were examined in the
presence of various inhibitors. Linear but not supercoiled DNA stimulated the
phosphorylation of several endogenous proteins in the extracts, including species
of approximately 48, 87, and 96 kDa. This phosphorylation was selectively
suppressed by the kinase inhibitors wortmannin, dimethylaminopurine, and
LY294002, with a dose response that in each case paralleled the inhibition of DNA
end-joining. If wortmannin was added while the end-joining reaction was in
progress, end-joining of DNA already present in the reaction continued for some
time, but newly added DNA was not joined or processed at all. Ends with 3'
hydroxyl termini were joined much faster than those with 3'-phosphoglycolate
termini, although both were equally effective in stimulating protein
phosphorylation. The results support a role for DNA-dependent protein kinase in
regulating end-joining in vitro, and suggest that at least one of the necessary
phosphorylations involves a protein bound at or near the DNA end to be joined. In
contrast, nuclear extracts from human cells joined double-strand breaks with
normal but not modified termini, and the joining was unaffected by kinase
inhibitors, suggesting that the dominant mechanism of end-joining in these
extracts did not involve DNA-PK.
PMID- 9657697
TI - The terminal adenosine of tRNA(Gln) mediates tRNA-dependent amino acid
recognition by glutaminyl-tRNA synthetase.
AB - Sequence-specific interactions between Escherichia coli glutaminyl-tRNA
synthetase and tRNA(Gln) have been shown to determine the apparent affinity of
the enzyme for its cognate amino acid glutamine during aminoacylation.
Specifically, structural and biochemical studies suggested that residues Asp66,
Tyr211, and Phe233 in glutaminyl-tRNA synthetase could potentially facilitate
cognate amino recognition through their specific interactions with both A76 of
tRNA(Gln)++ and glutamine. These residues were randomly mutated and the resulting
glutaminyl-tRNA synthetase variants were screened in vivo for changes in their
ability to recognize noncognate tRNAs and retention of tRNA-glutaminylation
activity. When the variants selected in this way were characterized in vitro,
they all showed dramatic decreases in apparent affinity (KM) for glutamine but
little or no change in cognate tRNA affinity. Conservative replacements such as
Y211F, F233L, and D66E resulted in 60-, 19-, and 18-fold increases compared to
wild-type in the KM for glutamine, respectively, but had little effect on the
turnover number (kcat). Nonconservative replacements affected both KM for
glutamine and kcat; Y211S, F233D, and D66F displayed 1700, 3700, and 1200-fold
decreases in kcat/KM for glutamine compared to wild-type. Double mutant cycle
analysis indicated that Tyr211, and Phe233 interact strongly to enhance glutamine
binding. These data now show that Asp66, Tyr211 and Phe233 mediate tRNA-dependent
cognate amino acid recognition via the invariant 3'-terminal adenosine of
tRNA(Gln).
PMID- 9657698
TI - Specific isoprenyl group linked to transducin gamma-subunit is a determinant of
its unique signaling properties among G-proteins.
AB - Among 11 subtypes of heterotrimeric G-protein gamma-subunit, gamma1 (rod), gamma8
(cone) and gamma11 are modified with farnesyl while the others are modified with
geranylgeranyl at the C-terminus. To understand the role of specific
isoprenylation (farnesylation) of retinal transducin, we examined how and to what
extent the type of isoprenyl group affects transducin-beta gamma (beta1 gamma1)
functions such as interactions with membranes, Galpha/receptor, and effectors. To
this end, the C-terminal farnesylation signal sequence (CVIS) of gamma1 was
replaced by a geranylgeranylation signal (CVIL), and the resultant mutant (S74L)
or wild-type (WT) gamma1 was coexpressed with beta1 in the baculovirus-Tn5 insect
cell system. Both gamma1WT and gamma1S74L expressed as a beta gamma complex were
mixtures modified with farnesyl and geranylgeranyl groups. The ratio of farnesyl
to geranylgeranyl in preparations of beta1 gamma1WT and beta1 gamma1S74L purified
from the Tn5 cell membrane fraction was about 1:2 and 1:6, respectively. These
two forms of recombinant beta1 gamma1 and retinal beta1 gamma1 were different in
their abilities to associate with rod outer segment membranes with the following
rank order: beta1 gamma1S74L > beta1 gamma1WT > retinal beta1 gamma1.
Functionally, beta1 gamma1S74L was the most potent to promote pertussis toxin
catalyzed ADP ribosylation of transducin-alpha (Talpha), to stimulate
metarhodopsin II-catalyzed GTPgammaS-binding reaction to Talpha and to modulate
adenylyl cyclase and phospholipase C activities. All of the beta1 gamma1
functions absolutely required the isoprenylation of the gamma-subunit. As for the
interaction with Goalpha and adenylyl cyclase, predominantly geranylgeranylated
beta1 gamma1S74L was less effective than geranylgeranylated beta1 gamma2 purified
from bovine brain. These results demonstrate that the properties of Gbeta gamma
are strongly affected by the type of functionally indispensable isoprenylation in
addition to the amino acid sequence of Ggamma. The relative contribution of the
two factors depends on proteins with which Gbeta gamma interacts.
PMID- 9657699
TI - Roles of individual disulfide bonds in the stability and folding of an omega
conotoxin.
AB - Although it contains only 25 amino acid residues, omega-conotoxin MVIIA folds
into a well-defined three-dimensional structure that is stabilized by 3 disulfide
bonds. To assess the contributions of the disulfides to folding and stability,
three analogues, each with one pair of disulfide-bonded Cys residues replaced
with Ala, were prepared and characterized. The analogues also contained a C
terminal Gly residue that is believed to be present when the peptide folds in
vivo and has been shown previously to stabilize the native structure. Circular
dichroism spectra and biological assays of the analogues indicated that removing
any one of the disulfides greatly destabilized the native conformation. The two
disulfides in each analogue were also reduced much more rapidly than in the
native form with three disulfides. When the analogues were fully reduced and
allowed to form disulfides in the presence of oxidized and reduced glutathione,
the native disulfides were not formed in preference to non-native disulfides,
further indicating that the forms with two-native disulfides are not
significantly stabilized by noncovalent interactions. However, the measured
equilibrium constants for disulfide formation indicate that forming any two of
the three native disulfides leads to an effective concentration of approximately
25-50 M for the two remaining thiols. The two-disulfide analogues thus appear to
represent a stage of folding in which the polypeptide is constrained to a
distribution of relatively compact conformations that greatly favor formation of
the third disulfide and the final folded structure.
PMID- 9657701
TI - Retroviral envelope glycoprotein processing: structural investigation of the
cleavage site
PMID- 9657702
TI - Elsewhere in biology
PMID- 9657700
TI - Probing the nucleotide binding sites of axonemal dynein with the fluorescent
nucleotide analogue 2'(3')-O-(-N-Methylanthraniloyl)-adenosine 5'-triphosphate.
AB - MantATP [2'(3')-O-(-N-methylanthraniloyl)-adenosine 5'-triphosphate] was employed
as a fluorescence probe of the nucleotide-binding sites of dynein from sea urchin
sperm flagella. MantATP binds specifically with enhanced fluorescence
(approximately 2.2-fold), homogeneous lifetime (8.4 ns), and high anisotropy (r
approximately 0.38) to dynein and can be displaced by ATP and ADP added to the
medium. The association constants of mantATP complexed with dynein were
determined from anisotropy titration data. Using a multiple stepwise equilibrium
model, the average values of the first two association constants are K1 = 2.7 x
10(5) M-1 and K2 = 1.8 x 10(4) M-1. This value of K1 is 7-8 times higher than
that found previously for unsubstituted ATP, whereas K2 is little changed [Mocz
and Gibbons (1996) Biochemistry 35, 9204-9211]. The lower-affinity binding sites,
K3 and K4, observed previously could not be studied with mantATP within the
available protein concentrations. The alpha and beta heavy chain subfractions
have binding parameters similar to those of intact dynein. Formation of the
stable ternary complex of mantATP with dynein and monomeric vanadate is
accompanied by only a moderate increase in the binding affinities. Oligomeric
vanadate reduces the binding affinities by approximately 50%. Addition of TritonX
100, methanol, or various salts changes the binding affinities by up to 50%,
suggesting that the microenvironment of the nucleotide-binding sites involves
significant contributions from both polar and apolar interactions. The distinct
affinities of the individual binding sites are consistent with a physiological
role in regulating nucleotide binding.
PMID- 9657703
TI - Downstream in America.
PMID- 9657704
TI - MCS: a sensitive issue.
PMID- 9657705
TI - Trial and error: should pregnant women be research subjects?
PMID- 9657706
TI - Rock 'n' Roll Refrigerator.
PMID- 9657707
TI - Comparative activity of human carcinogens and NTP rodent carcinogens in the mouse
bone marrow micronucleus assay: an integrative approach to genetic toxicity data
assessment.
AB - The mouse bone marrow micronucleus (MN) assay holds a key position in all schemes
for detecting potential human carcinogens and mutagens. It was therefore of
concern when Shelby et al. reported that only 5 of 25 rodent carcinogens defined
by the U.S. NTP were positive in the assay. Further, each of these positive
responses was weak and indistinguishable from the 4 positive responses observed
among the 24 NTP noncarcinogens tested. To focus these findings, the activity in
the MN assay of 26 human carcinogens, 6 reference rodent genotoxins, and the 9
NTP chemicals positive in the MN assay have been displayed in a common format.
This involved plotting the minimum positive dose level (expressed as
mumole/kilogram) and the maximum fold-increase in micronucleated polychromatic
erythrocytes frequency observed at any dose level. By displaying the high
sensitivity of the micronucleus assay to the reference human and rodent
genotoxins, this analysis emphasizes the weakness in the MN assay responses given
by the NTP carcinogens reported by Shelby et al. This, in turn, poses questions
about the intrinsic hazard of this selection of NTP rodent carcinogens. Using
fotemustine and vitamin C as models of a toxic and a nontoxic chemical known to
be active in the MN assay, this analysis describes a method by which their
relative potential human hazard can be distinguished (a synthetic, as opposed to
an analytical approach to data assessment). The possibility that some weak
responses observed in the MN assay at elevated dose levels may be stress induced
is considered.
PMID- 9657708
TI - A biomarker approach to assessing xenobiotic exposure in Atlantic tomcod from the
North American Atlantic coast.
AB - We determined levels of hepatic cytochrome P4501A (CYP1A) mRNA, hepatic DNA
adducts, and fluorescent aromatic compounds (FACs) in bile, a measure of exposure
to polyaromatic hydrocarbons, in Atlantic tomcod from six river systems ranging
from highly polluted to relatively pristine on the northeast North American coast
(the Hudson River, New York; the St. Lawrence River, Quebec; the Miramichi River,
New Brunswick; the Saco and Royal rivers, Maine; and the Margaree River, Nova
Scotia). Hudson River tomcod showed the greatest response for all parameters, and
tomcod from the Margaree River exhibited the least response. Tomcod from the
Miramichi River exhibited marked induction of CYP1A mRNA but low levels of
hepatic DNA adducts and biliary FACs, whereas fish from the St. Lawrence River
showed no induction of CYP1A mRNA and moderately elevated levels of DNA adducts
and biliary FACs. In tomcod from the Hudson and Miramichi rivers, the levels of
CYP1A mRNA were 28 times and 14 times, respectively, as great as the levels in
fish from the St. Lawrence, Saco/Royal, and Margaree rivers. Mean levels of DNA
adducts varied from 120 nmol adducts/mol bases in Hudson River tomcod to < 3 nmol
adducts/mol bases in fish from the Miramichi and Margaree rivers. Concentrations
of FACs in the bile of tomcod from the Hudson and St. Lawrence rivers were 8 and
1.8 times, respectively, as great as the concentrations in tomcod from the
Miramichi River and Margaree River. In tomcod from the Hudson River, all three
biomarkers were markedly elevated; in the St. Lawrence River two biomarkers were
elevated, in the Miramichi River one was elevated, but no biomarker was
substantially elevated in fish from the Saco/Royal and Margaree rivers. Elevated
levels of hepatic DNA adducts and biliary FACs in tomcod from the Hudson River
suggest increased exposure to PAHs, consistent with previous studies.
PMID- 9657709
TI - High levels of mercury contamination in multiple media of the Carson River
drainage basin of Nevada: implications for risk assessment.
AB - Approximately 5.5 x 109 g (4.0 x 105) of mercury was discharged into the Carson
River Drainage Basin of west-central Nevada during processing of the gold- and
silver-rich Comstock ore in the late 1800s. For the past 13 decades, mercury has
been redistributed throughout 500 km2 of the basin, and concentrations are some
of the highest reported values in North America. This article documents the
concentrations of mercury in the air, water, and substrate at both contaminated
and noncontaminated sites within the basin and discusses the implications for
risk assessment. At contaminated areas, the range of mercury concentrations are
as follows: mill tailings, 3-1610 micrograms/g; unfiltered reservoir water, 53
591 ng/l; atmospheric vapor, 2-294 ng/m3. These values are three to five orders
of magnitude greater than natural background. In all media at contaminated sites,
concentrations are spatially variable, and air and water mercury concentrations
vary temporally. The study are in situated in a natural mercuriferous belt, and
regional background mercury concentrations in all environmental media are higher
than values typically cited for natural background. As a mercury-contaminated
site in North America, the Carson River Drainage Basin is unusual for a number of
reasons, including its location in a natural mercuriferous belt, high and
sustained levels of anthropogenic mercury inputs, long exposure time, aridity of
the climate, and the riparian setting in an arid landscape, where biological
activity is concentrated in the same areas that contain high levels of mercury in
multiple media.
PMID- 9657710
TI - PCBs as environmental estrogens: turtle sex determination as a biomarker of
environmental contamination.
AB - Polychlorinated biphenyls (PCBs) are widespread, low-level environmental
pollutants associated with adverse health effects such as immune suppression and
teratogenicity. There is increasing evidence that some PCB compounds are capable
of disrupting reproductive and endocrine function in fish, birds, and mammals,
including humans, particularly during development. Research on the mechanism
through which these compounds act to alter reproductive function indicates
estrogenic activity, whereby the compounds may be altering sexual
differentiation. Here we demonstrate the estrogenic effect of some PCBs by
reversing gonadal sex in a reptile species that exhibits temperature-dependent
sex determination.
PMID- 9657711
TI - Major bacterial contribution to marine dissolved organic nitrogen
AB - Next to N2 gas, the largest pool of reduced nitrogen in the ocean resides in the
enormous reservoir of dissolved organic nitrogen (DON). The chemical identity of
most of this material, and the mechanisms by which it is cycled, remain
fundamental questions in contemporary oceanography. Amino acid enantiomeric
ratios in the high molecular weight fraction of DON from surface and deep water
in three ocean basins show substantial enrichment in D enantiomers of four amino
acids. The magnitude and pattern of these D/L enrichments indicate that
peptidoglycan remnants derived from bacterial cell walls constitute a major
source of DON throughout the sea. These observations suggest that structural
properties of specific bacterial biopolymers, and the mechanisms for their
accumulation, are among the central controls on long-term cycling of dissolved
organic nitrogen in the sea.
PMID- 9657712
TI - The CO2 balance of unproductive aquatic ecosystems
AB - Community respiration (R) rates are scaled as the two-thirds power of the gross
primary production (P) rates of aquatic ecosystems, indicating that the role of
aquatic biota as carbon dioxide sources or sinks depends on its productivity.
Unproductive aquatic ecosystems support a disproportionately higher respiration
rate than that of productive aquatic ecosystems, tend to be heterotrophic (R >
P), and act as carbon dioxide sources. The average P required for aquatic
ecosystems to become autotrophic (P > R) is over an order of magnitude greater
for marshes than for the open sea. Although four-fifths of the upper ocean is
expected to be net heterotrophic, this carbon demand can be balanced by the
excess production over the remaining one-fifth of the ocean.
PMID- 9657713
TI - Primary production of the biosphere: integrating terrestrial and oceanic
components
AB - Integrating conceptually similar models of the growth of marine and terrestrial
primary producers yielded an estimated global net primary production (NPP) of
104.9 petagrams of carbon per year, with roughly equal contributions from land
and oceans. Approaches based on satellite indices of absorbed solar radiation
indicate marked heterogeneity in NPP for both land and oceans, reflecting the
influence of physical and ecological processes. The spatial and temporal
distributions of ocean NPP are consistent with primary limitation by light,
nutrients, and temperature. On land, water limitation imposes additional
constraints. On land and ocean, progressive changes in NPP can result in altered
carbon storage, although contrasts in mechanisms of carbon storage and rates of
organic matter turnover result in a range of relations between carbon storage and
changes in NPP.
PMID- 9657714
TI - Abrupt shift in subsurface temperatures in the tropical pacific associated with
changes in El Nino
AB - Radiocarbon (14C) content of surface waters inferred from a coral record from the
Galapagos Islands increased abruptly during the upwelling season (July through
September) after the El Nino event of 1976. Sea-surface temperatures (SSTs)
associated with the upwelling season also shifted after 1976. The synchroneity of
the shift in both 14C and SST implies that the vertical thermal structure of the
eastern tropical Pacific changed in 1976. This change may be responsible for the
increase in frequency and intensity of El Nino events since 1976.
PMID- 9657715
TI - Solidus of Earth's deep mantle
AB - The solidus of a pyrolite-like composition, approximating that of the lower
mantle, was measured up to 59 gigapascals by using CO2 laser heating in a diamond
anvil cell. The solidus temperatures are at least 700 kelvin below the melting
temperatures of magnesiowustite, which in the deep mantle has the lowest melting
temperatures of the three major components-magnesiowustite, Mg-Si-perovskite, and
Ca-Si-perovskite. The solidus in the deep mantle is more than 1500 kelvin above
the average present-day geotherm, but at the core-mantle boundary it is near the
core temperature. Thus, partial melting of the mantle is possible at the core
mantle boundary.
PMID- 9657716
TI - A reduction-pyrolysis-catalysis synthesis of diamond
AB - Diamond powder was synthesized through a metallic reduction-pyrolysis-catalysis
route with the reaction of carbon tetrachloride and sodium at 700 degreesC, in
which the sodium was used as reductant and flux. This temperature is much lower
than that of traditional methods. The x-ray powder diffraction patterns showed
three strong peaks of diamond. The Raman spectrum showed a sharp peak at 1332
inverse centimeters, which is characteristic of diamond. Although the yield was
only 2 percent, this method is a simple means of forming diamond.
PMID- 9657717
TI - MR imaging contrast enhancement based on intermolecular zero quantum coherences.
AB - A new method for magnetic resonance imaging (MRI) based on the detection of
relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is
reported. Such a signal would not be observable in the conventional framework of
magnetic resonance; it originates in long-range dipolar couplings (10 micrometers
to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where
image contrast is based on variations in spin density and relaxation times (often
with injected contrast agents), contrast with iZQC images comes from variations
in the susceptibility over a distance dictated by gradient strength. Phantom and
in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This
contrast might be useful in the detection of small tumors, in that susceptibility
correlates with oxygen concentration and in functional MRI.
PMID- 9657718
TI - Evidence for the use of fire at zhoukoudian, china
AB - Zhoukoudian is widely regarded as having the oldest reliable evidence for the
controlled use of fire by humans. A reexamination of the evidence in Layer 10,
the earliest archaeological horizon in the site, shows that burned and unburned
bones are present in the same layer with stone tools. However, no ash or charcoal
remnants could be detected. Hence, although indirect evidence for burning is
present, there is no direct evidence for in situ burning.
PMID- 9657719
TI - Design of a 20-amino acid, three-stranded beta-sheet protein.
AB - A 20-residue protein (named Betanova) forming a monomeric, three-stranded,
antiparallel beta sheet was designed using a structural backbone template and an
iterative hierarchical approach. Structural and physicochemical characterization
show that the beta-sheet conformation is stabilized by specific tertiary
interactions and that the protein exhibits a cooperative two-state folding
unfolding transition, which is a hallmark of natural proteins. The Betanova
molecule constitutes a tractable model system to aid in the understanding of beta
sheet formation, including beta-sheet aggregation and amyloid fibril formation.
PMID- 9657720
TI - A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor [see
commetns].
AB - A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony
stimulating factor (G-CSF) signal transduction pathways, was identified in a high
throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine
phosphorylation of multiple signaling proteins and stimulated primary murine bone
marrow cells to form granulocytic colonies in vitro. It also elevated peripheral
blood neutrophil counts in mice. The extracellular domain of the murine G-CSF
receptor was required for the activity of SB 247464, suggesting that the compound
acts by oligomerizing receptor chains. The results indicate that a small molecule
can activate a receptor that normally binds a relatively large protein ligand.
PMID- 9657721
TI - Infrared MALDI mass spectrometry of large nucleic acids.
AB - Mass spectrometry has become an increasingly important tool of high accuracy,
efficiency, and speed for the routine analysis of nucleic acids. To make it
useful for large-scale sequencing of genomic material as required for example in
genotyping and clinical diagnosis, it is necessary to find approaches that allow
the analysis of sequences much larger than the 100 nucleotides currently
possible. Matrix-assisted laser desorption/ionization (MALDI) mass spectra of
synthetic DNA, restriction enzyme fragments of plasmid DNA, and RNA transcripts
up to a size of 2180 nucleotides are reported. The demonstrated mass accuracy of
1 percent or better and the sample requirement of a few femtomoles or less
surpass all currently available techniques for the analysis of large nucleic
acids. DNA and RNA can be analyzed with only a limited investment in sample
purification.
PMID- 9657722
TI - Structure of the Escherichia coli RNA polymerase alpha subunit amino-terminal
domain.
AB - The 2.5 angstrom resolution x-ray crystal structure of the Escherichia coli RNA
polymerase (RNAP) alpha subunit amino-terminal domain (alphaNTD), which is
necessary and sufficient to dimerize and assemble the other RNAP subunits into a
transcriptionally active enzyme and contains all of the sequence elements
conserved among eukaryotic alpha homologs, has been determined. The alphaNTD
monomer comprises two distinct, flexibly linked domains, only one of which
participates in the dimer interface. In the alphaNTD dimer, a pair of helices
from one monomer interact with the cognate helices of the other to form an
extensive hydrophobic core. All of the determinants for interactions with the
other RNAP subunits lie on one face of the alphaNTD dimer. Sequence alignments,
combined with secondary-structure predictions, support proposals that a
heterodimer of the eukaryotic RNAP subunits related to Saccharomyces cerevisiae
Rpb3 and Rpb11 plays the role of the alphaNTD dimer in prokaryotic RNAP.
PMID- 9657723
TI - Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to antiretroviral
agents.
AB - Expression of human immunodeficiency virus-type 1 (HIV-1) Vpr after productive
infection of T cells induces cell cycle arrest in the G2 phase of the cell cycle.
In the absence of de novo expression, HIV-1 Vpr packaged into virions still
induced cell cycle arrest. Naturally noninfectious virus or virus rendered
defective for infection by reverse transcriptase or protease inhibitors were
capable of inducing Vpr-mediated cell cycle arrest. These results suggest a model
whereby both infectious and noninfectious virions in vivo, such as those
surrounding follicular dendritic cells, participate in immune suppression.
PMID- 9657724
TI - Specific covalent labeling of recombinant protein molecules inside live cells.
AB - Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5
positions of an alpha helix were fluorescently labeled in living cells by
extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein.
This designed small ligand is membrane-permeant and nonfluorescent until it binds
with high affinity and specificity to the tetracysteine domain. Such in situ
labeling adds much less mass than does green fluorescent protein and offers
greater versatility in attachment sites as well as potential spectroscopic and
chemical properties. This system provides a recipe for slightly modifying a
target protein so that it can be singled out from the many other proteins inside
live cells and fluorescently stained by small nonfluorescent dye molecules added
from outside the cells.
PMID- 9657726
TI - Growth factors and hematopoietic cell fate. A new feature: controversies in
hematology
PMID- 9657725
TI - Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage
checkpoint.
AB - The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints
that prevent cell division in cells with damaged or incompletely replicated DNA.
The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated
Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain
of Rad53. Inactivation of this domain abolished DNA damage-dependent Rad53
phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription
but did not affect replication inhibition-dependent Rad53 phosphorylation. Thus,
Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The
hitherto uncharacterized FHA domain appears to be a modular protein-binding
domain.
PMID- 9657727
TI - Lineage commitment and maturation in hematopoietic cells: the case for extrinsic
regulation.
PMID- 9657729
TI - Rebuttal to enver, heyworth, and dexter
PMID- 9657728
TI - Do stem cells play dice?
PMID- 9657730
TI - Rebuttal to metcalf
PMID- 9657731
TI - Specific signals generated by the cytoplasmic domain of the granulocyte colony
stimulating factor (G-CSF) receptor are not required for G-CSF-dependent
granulocytic differentiation.
AB - Granulocyte colony-stimulating factor (G-CSF) is the principal growth factor
regulating the production of neutrophils, yet its role in lineage commitment and
terminal differentiation of hematopoietic progenitor cells is controversial. In
this study, we describe a system to study the role of G-CSF receptor (G-CSFR)
signals in granulocytic differentiation using retroviral transduction of G-CSFR
deficient, primary hematopoietic progenitor cells. We show that ectopic
expression of wild-type G-CSFR in hematopoietic progenitor cells supports G-CSF
dependent differentiation of these cells into mature granulocytes, macrophages,
megakaryocytes, and erythroid cells. Furthermore, we show that two mutant G-CSFR
proteins, a truncation mutant that deletes the carboxy-terminal 96 amino acids
and a chimeric receptor containing the extracellular and transmembrane domains of
the G-CSFR fused to the cytoplasmic domain of the erythropoietin receptor, are
able to support the production of morphologically mature, chloroacetate esterase
positive, Gr-1/Mac-1-positive neutrophils in response to G-CSF. These results
demonstrate that ectopic expression of the G-CSFR in hematopoietic progenitor
cells allows for multilineage differentiation and suggest that unique signals
generated by the cytoplasmic domain of the G-CSFR are not required for G-CSF
dependent granulocytic differentiation.
PMID- 9657733
TI - Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia.
AB - T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia
associated with chromosomal rearrangements implicating MTCP1 or TCL1 genes. These
genes encode two homologous proteins, p13(MTCP1) and p14(TCL1), which share no
similarity with other known protein. To determine the oncogenic role of MTCP1,
mice transgenic for MTCP1 under the control of CD2 regulatory regions (CD2-p13
mice) were generated. No abnormality was detected during the first year after
birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13
mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid
hemopathies, occurring in the three transgenic lines, were characterized by
lymphoid cells with an irregular nucleus, a unique and prominent nucleolus,
condensed chromatin, a basophilic cytoplasm devoid of granules, and an
immunophenotype of mature T cells. The molecular characterization of Tcrb
rearrangements demonstrated the monoclonal origin of these populations.
Histopathological analysis of the cohort demonstrated early splenic and hepatic
infiltrations, whereas lymphocytosis and medullar infiltrations were found
infrequently. The engraftment of these proliferations in H2-matched animals
demonstrated their malignant nature. Cumulative incidence of the disease at 20
months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in
the control group. The level of expression of the transgene, as estimated by
Western blotting in the transgenic lines correlated with the tumoral incidence,
with the highest expression of p13(MTCP1) being found in F3 mice. CD2-p13
transgenic mice developed an hemopathy similar to human T-PLL. These data
demonstrate that p13(MTCP1) is an oncoprotein and that CD2-p13 transgenic mice
represent the first animal model for mature T-PLL.
PMID- 9657732
TI - Evidence for circulating bone marrow-derived endothelial cells.
AB - It has been proposed that hematopoietic and endothelial cells are derived from a
common cell, the hemangioblast. In this study, we demonstrate that a subset of
CD34(+) cells have the capacity to differentiate into endothelial cells in vitro
in the presence of basic fibroblast growth factor, insulin-like growth factor-1,
and vascular endothelial growth factor. These differentiated endothelial cells
are CD34(+), stain for von Willebrand factor (vWF), and incorporate acetylated
low-density lipoprotein (LDL). This suggests the possible existence of a bone
marrow-derived precursor endothelial cell. To demonstrate this phenomenon in
vivo, we used a canine bone marrow transplantation model, in which the marrow
cells from the donor and recipient are genetically distinct. Between 6 to 8
months after transplantation, a Dacron graft, made impervious to prevent
capillary ingrowth from the surrounding perigraft tissue, was implanted in the
descending thoracic aorta. After 12 weeks, the graft was retrieved, and cells
with endothelial morphology were identified by silver nitrate staining. Using the
di(CA)n and tetranucleotide (GAAA)n repeat polymorphisms to distinguish between
the donor and recipient DNA, we observed that only donor alleles were detected in
DNA from positively stained cells on the impervious Dacron graft. These results
strongly suggest that a subset of CD34+ cells localized in the bone marrow can be
mobilized to the peripheral circulation and can colonize endothelial flow
surfaces of vascular prostheses.
PMID- 9657734
TI - Mutations in the E-domain of RAR portion of the PML/RAR chimeric gene may confer
clinical resistance to all-trans retinoic acid in acute promyelocytic leukemia.
AB - The binding of all-trans retinoic acid (ATRA) to the ligand-binding region in the
E-domain of retinoic acid receptor-alpha modifies the transcriptional activity of
RARalpha protein. ATRA probably induces differentiation of acute promyelocytic
leukemia (APL) cells by binding to the E-domain of the RARalpha portion (RARalpha
/E-domain) of PML/RARalpha chimeric protein. Therefore, molecular alteration in
the RARalpha /E-domain of the chimeric gene is one mechanism by which patients
with APL may acquire resistance to ATRA therapy. In this study using reverse
transcription-polymerase chain reaction and single-strand conformation
polymorphism, DNA segments amplified from the RARalpha /E-domain in fresh APL
cells of 23 APL patients (8 males and 15 females from 4 to 76 years of age) were
screened for mutations. Of those patients, 3 patients (1 with de novo and 2 with
relapse) had clinical resistance to ATRA therapy. We found mutations in the
RARalpha /E-domain of PML/RARalpha chimeric gene exclusively in the 2 patients
who exhibited ATRA-resistance at relapse, whereas the mutations were not detected
at their initial onset. Interestingly, these patients received a prolonged or
intermittent administration of ATRA before relapse with ATRA-resistance. The
mutations lead to the change of amino acid in the ligand-binding region of
RARalpha /E-domain, Arg272Gln, or Met297Leu according to the amino acid sequence
of RARalpha, respectively. Further study demonstrated that the in vitro ligand
dependent transcriptional activity of the mutant PML/RARalpha protein was
significantly decreased as compared with that of wild-type PML/RARalpha. These
findings suggest that mutations in the RARalpha /E-domain of the PML/RARalpha
chimeric gene may confer clinical resistance to ATRA therapy in patients with
APL.
PMID- 9657735
TI - Loss of function of the homeobox gene Hoxa-9 perturbs early T-cell development
and induces apoptosis in primitive thymocytes.
AB - Hox homeobox genes play a crucial role in specifying the embryonic body pattern.
However, a role for Hox genes in T-cell development has not been explored. The
Hoxa-9 gene is expressed in normal adult and fetal thymuses. Fetal thymuses of
mice homozygous for an interruption of the Hoxa-9 gene are one eighth normal size
and have a 25-fold decrease in the number of primitive thymocytes expressing the
interleukin-2 receptor (IL-2R, CD25). Progression to the double positive
(CD4+CD8+) stage is dramatically retarded in fetal thymic organ cultures. This
aberrant development is associated with decreased amounts of intracellular CD3
and T-cell receptor beta (TCRbeta) and reduced surface expression of IL-7R and E
cadherin. Mutant thymocytes show a significant increase in apoptotic cell death
and premature downregulation of bcl-2 expression. A similar phenotype is seen in
primitive thymocytes from adult Hoxa-9-/- mice and from mice transplanted with
Hoxa-9-/- marrow. Hoxa-9 appears to play a previously unsuspected role in T-cell
ontogeny by modulating cell survival of early thymocytes and by regulating their
subsequent differentiation.
PMID- 9657736
TI - Association between pretransplant interferon-alpha and outcome after unrelated
donor marrow transplantation for chronic myelogenous leukemia in chronic phase.
AB - Treatment options for patients diagnosed with chronic myelogenous leukemia (CML)
in chronic phase (CP) who lack a suitable related donor for marrow
transplantation include hydroxyurea, interferon-alpha (IFN-alpha), or
transplantation from an unrelated donor (URD). Most studies support the view that
treatment with IFN-alpha results in prolonged survival compared with hydroxyurea
therapy. Some patients are offered URD transplantation as a second-line
treatment; however, the impact of pretransplant IFN-alpha on the outcome of URD
transplantation is uncertain. To address this question, we evaluated the effect
of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation
for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN
alpha, whereas 22, 23, and 25 patients received IFN-alpha for, respectively, 1 to
5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha
therapy administered for > or = 6 months was associated with an increased risk of
severe (grades III-IV) acute graft-versus-host disease (GVHD; relative risk [RR],
3.0; 95% confidence interval [CI], 1.4 to 6.2; P = .004) and mortality (RR, 2. 1;
95% CI, 1.3 to 3.5; P = .003) relative to less than 6 months or no IFN-alpha
therapy. Increased mortality occurred between 100 and 365 days after transplant
(P = .005), was limited to patients with severe acute GVHD, and was due to
chronic GVHD refractory to immunosuppressive therapy. Other variables associated
with mortality included HLA-DRB1 or DQB1 (but not HLA-A or B) mismatched donors,
age greater than 50 years, weight > or = 110% of ideal body weight, and the
absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with
IFN-alpha for less than 6 months before transplant, who were < or = 50 years of
age, received a HLA-A, B, DRB1, and DQB1 matched URD transplant, and received CMV
and fungal prophylaxis after transplant (n = 48), survival was 87% +/- 5% at 5
years. These data provide a rationale for immediate transplantation in preference
to extended treatment with IFN-alpha when the patient is < or = 50 years of age
and has an HLA-compatible unrelated volunteer donor.
PMID- 9657737
TI - Blood dendritic cells from myeloma patients are not infected with Kaposi's
sarcoma-associated herpesvirus (KSHV/HHV-8).
AB - In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus
(KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of
patients with multiple myeloma (MM). A concern was raised whether there is an
causal association between the viral infection and development of these tumors.
In the present study, we have examined DC generated from blood adherent cells
from 8 Swedish MM patients at different clinical stages and 2 patients with
monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell
lines and bone marrow cells from 2 MM patients were also studied. By polymerase
chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the
patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no
antibody against KSHV was found in the serum of these 10 patients. Thus, our
results indicate that blood-derived DC of MM patients in Sweden usually are not
infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not
regularly associated with MM and consequently does not play a primary role in the
pathogenesis of these tumors.
PMID- 9657738
TI - A risk model for thrombocytopenia requiring platelet transfusion after cytotoxic
chemotherapy.
AB - Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic
chemotherapy for which risk factors are not well known. Our objective was to
delineate a risk model for chemotherapy-induced thrombocytopenia requiring
platelet transfusions in cancer patients. Univariate and multivariate analysis of
risk factors for chemotherapy-induced thrombocytopenia requiring platelet
transfusions were performed on the cohort of the 1,051 patients (CLB 1996)
treated with chemotherapy in the Department of Medicine of the Centre Leon Berard
(CLB) in 1996. In univariate analysis, performance status (PS) greater than 1,
platelet count less than 150, 000/microL at day 1 (d1) before the initiation of
chemotherapy, d1 lymphocyte count < or = 700/microL, d1 polymorphonuclear
leukocyte count less than 1,500/microL, and the type of chemotherapy (high risk v
others) were significantly associated (P < .01) with an increased risk of severe
thrombocytopenia requiring platelet transfusions. Using logistic regression, d1
platelet count less than 150,000/microL (odds ratio [OR], 4.3; 95% confidence
interval [CI], 1.9 to 9.6), d1 lymphocyte counts < or = 700/microL (OR, 3.37; 95%
CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and
PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent
risk factors for platelet transfusions. The observed incidences of platelet
transfusions were 45%, 13%, 7%, and 1.5% for patients with > or = 3, 2, 1, or 0
risk factors, respectively. This model was then tested in 3 groups of patients
treated with chemotherapy used as validation samples: (1) the series of 340
patients treated in the CLB in the first 6 months of 1997, (2) the prospective
multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of
149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective
phase III trials (1987 to 1995). In these 3 groups, the observed incidences of
platelet transfusions in the above-defined risk groups did not differ
significantly (P > .1) from those calculated in the model. This risk index could
be useful to identify patients at high risk for chemotherapy-induced
thrombocytopenia requiring platelet transfusions.
PMID- 9657739
TI - Early intensification of intrathecal chemotherapy virtually eliminates central
nervous system relapse in children with acute lymphoblastic leukemia.
AB - Central nervous system (CNS) relapse has been an obstacle to uniformly successful
treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We
therefore intensified intrathecal chemotherapy (simultaneously administered
methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with
newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to
August 1994. The 64 patients (39%) who had 1 or more blast cells in
cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without
associated higher-risk features, received additional doses of intrathecal
chemotherapy during remission induction and the first year of continuation
treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid
findings, also received additional doses of intrathecal chemotherapy during the
first year of continuation treatment. Cranial irradiation was reserved for
patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk
of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence
interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0. 4% to 6.0%).
The probability of surviving for 5 years without an adverse event of any type was
80.2% +/- 9.2% (SE). Our results suggest that early intensification of
intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level
in children with ALL, securing a higher event-free survival rate overall.
PMID- 9657740
TI - Granulocyte-macrophage colony-stimulating factor rescues TF-1 leukemia cells from
ionizing radiation-induced apoptosis through a pathway mediated by protein kinase
Calpha.
AB - Protein kinase C (PKC) activity has a recognized role in mediating apoptosis.
However, the role of individual PKC isoforms in apoptosis is poorly defined.
Therefore, we investigated the translocation of individual PKC isoforms during
radiation-induced apoptosis with and without rescue from apoptosis by granulocyte
macrophage colony-stimulating factor (GM-CSF) in the human erythroleukemia cell
line TF-1. PKCalpha was translocated from the particulate to cytosolic fraction
of TF-1 cells within 5 minutes of treatment with apoptosis-inducing levels of
ionizing radiation. However, this postirradiation translocation did not occur
when cells were rescued from apoptosis by GM-CSF. Furthermore, treatment of cells
with Go 6976, an inhibitor of classical PKC isoforms, abrogated the rescue effect
of GM-CSF. The calcium-independent novel PKC isoform, PKCalpha appeared to be
degraded in both the particulate and cytosolic fractions of TF-1 cells after
treatment with apoptosis-inducing levels of ionizing radiation in either the
presence or absence of GM-CSF rescue. Levels of ceramide, a lipid mediator of
apoptosis, were measured at 2, 4, 8, 10, and 60 minutes after treatment with
ionizing radiation and were substantially reduced in TF-1 cells rescued from
apoptosis by GM-CSF compared with apoptotic TF-1 cells. The largest decrease in
ceramide production seen was at 4 minutes postirradiation, with a 46% reduction
in ceramide levels in TF-1 cells rescued from apoptosis by GM-CSF compared with
those in apoptotic TF-1 cells. Because ceramide has been shown to affect PKCalpha
subcellular distribution, these data implicate a role for ceramide in mediating
the rapid postirradiation translocation and inhibition of PKCalpha in TF-1 cells
not rescued from apoptosis by GM-CSF. Expression of the antiapoptotic protein Bcl
2 doubled in TF-1 cells rescued from apoptosis by GM-CSF, but did not increase in
unrescued cells. Our findings suggest that activated PKCalpha and increased
expression of Bcl-2 after gamma irradiation determine survival in TF-1 cells
rescued from apoptosis with GM-CSF and that PKCalpha plays a role in mediating
signals involved in sensing cellular damage and/or regulation of cell damage
repair.
PMID- 9657741
TI - The hyperresponsiveness of cells expressing truncated erythropoietin receptors is
contingent on insulin-like growth factor-1 in fetal calf serum.
AB - We demonstrate herein that the well documented hyperresponsiveness to
erythropoietin (Epo) of Ba/F3 cells expressing C-terminal truncated
erythropoietin receptors (EpoRs) is contingent on these cells being in fetal calf
serum (FCS). In the absence of FCS, their Epo-induced proliferation is far poorer
than Ba/F3 cells expressing wild-type (WT) EpoRs. This hyporesponsiveness in the
absence of serum is also seen in DA-3 cells expressing these truncated EpoRs. In
fact, long-term proliferation studies performed in the absence of serum show that
even at saturating concentrations of Epo, Ba/F3 cells expressing these truncated
receptors die via apoptosis, while cells bearing WT EpoRs do not, and this
programmed cell death correlates with an inability of Epo-stimulated Ba/F3 cells
expressing truncated EpoRs to induce the tyrosine phosphorylation of MAPK and the
activation of p70(S6K). Using neutralizing antibodies to insulin-like growth
factor (IGF)-1, we show that a major non-Epo factor in FCS that contributes to
the hyperresponsive phenotype of Ba/F3 cells expressing truncated EpoRs is IGF-1.
Our results suggest that the Epo-hypersensitivity of truncated EpoR expressing
Ba/F3 cells is due to the combined effects of these EpoRs not possessing a
binding site for the negative regulator, SHP-1, and the triggering of
proliferation-inducing/apoptosis-inhibiting cascades, lost through EpoR
truncation, by IGF-1.
PMID- 9657742
TI - Role of GATA-1 in proliferation and differentiation of definitive erythroid and
megakaryocytic cells in vivo.
AB - To elucidate the contributions of GATA-1 to definitive hematopoiesis in vivo, we
have examined adult mice that were rendered genetically defective in GATA-1
synthesis (Takahashi et al, J Biol Chem 272:12611, 1997). Because the GATA-1 gene
is located on the X chromosome, which is randomly inactivated in every cell,
heterozygous females can bear either an active wild-type or mutant (referred to
as GATA-1.05) GATA-1 allele, consequently leading to variable anemic severity.
These heterozygous mutant mice usually developed normally, but they began to die
after 5 months. These affected animals displayed marked splenomegaly, anemia, and
thrombocytopenia. Proerythroblasts and megakaryocytes massively accumulated in
the spleens of the heterozygotes, and we showed that the neomycin resistance gene
(which is the positive selection marker in ES cells) was expressed profusely in
the abnormally abundant cells generated in the GATA-1.05 mutant females. We also
observed hematopoiesis outside of the bone marrow in the affected mutant mice.
These data suggest that a small number of GATA-1.05 mutant hematopoietic
progenitor cells begin to proliferate vigorously during early adulthood, but
because the cells are unable to terminally differentiate, this leads to
progenitor proliferation in the spleen and consequently death. Thus, GATA-1 plays
important in vivo roles for directing definitive hematopoietic progenitors to
differentiate along both the erythroid and megakaryocytic pathways. The GATA-1
heterozygous mutant mouse shows a phenotype that is analogous to human
myelodysplastic syndrome and thus may serve as a useful model for this disorder.
PMID- 9657743
TI - Erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and STAT5B in
primary cultured human erythroid precursors.
AB - We examined signaling by erythropoietin in highly purified human colony forming
unit-erythroid cells, generated in vitro from CD34(+) cells. We found that
erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and STAT5B.
Tyrosine phosphorylation of Jak2 reaches a peak around 10 minutes after
stimulation and is maximum at 5 U/mL of erythropoietin. Tyrosine phosphorylation
of STAT5 is accompanied by the translocation of activated STAT5 to the nucleus as
shown by electrophoretic mobility shift assay (EMSA) using 32Pi-labeled STAT5
binding site in the beta-casein promoter. Tyrosine phosphorylation STAT1 or STAT3
was not detected in human erythroid precursors after stimulation with
erythropoietin. Crkl, an SH2/SH3 adapter protein, becomes coimmunoprecipitated
specifically with STAT5 from erythropoietin-stimulated erythroid cells; although
it was shown to become associated with c-Cbl in the studies using cell lines.
Thus, human erythroid precursors can be expanded in vitro in sufficient numbers
and purity to allow its usage in signal transduction studies. This report sets a
basis for further studies on signaling in primary cultured human erythroid
precursors, which in turn contribute to our better understanding in the
differentiation processes of erythrocytes and their precursors.
PMID- 9657744
TI - Thrombopoietin promotes the survival of murine hematopoietic long-term
reconstituting cells: comparison with the effects of FLT3/FLK-2 ligand and
interleukin-6.
AB - The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and
interleukin-6 (IL-6) on the survival of murine hematopoietic long-term
reconstituting cells (LTRC) were studied by using lineage-negative, Sca-1
positive, c-kit-positive (Lin-Sca-1(+)c-kit+) marrow cells from 5-fluorouracil
treated mice. We tested the ability of these cytokines to maintain the viability
of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic
mice together with compromised marrow cells. As a single agent, only TPO could
maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted
synergistically to maintain the LTRC. We examined whether the maintenance of LTRC
by these cytokines was due to the survival of stem cells or was the result of
active cell divisions and self-renewal. To monitor cell division, we used
membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated
in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7,
PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo
reconstituting abilities were tested by transplantation into lethally irradiated
Ly-5 congenic mice together with compromised marrow cells. PKH26(high)
populations cultured with both TPO alone and the combination of IL-6 and FL
showed greater reconstitution activity than that of PKH26(low) populations. These
data indicate that TPO alone and the combination of IL-6 and FL can support the
survival of stem cells without stimulating their active cell proliferation.
PMID- 9657745
TI - A novel function of Stat1 and Stat3 proteins in erythropoietin-induced erythroid
differentiation of a human leukemia cell line.
AB - We recently determined that erythropoietin (EPO) activates 3 members of the
signal transducer and activator of transcription (STAT) family, Stat1alpha,
Stat3, and Stat5, in the human EPO-dependent cell lines, UT-7 and UT-7/EPO
(Kirito et al, J Biol Chem 272:16507, 1997). In addition, we have shown that
Stat1alpha, but not Stat3, is involved in EPO-induced cellular proliferation. In
this study, we examined the roles of Stat1alpha and Stat3 in EPO-induced
erythroid differentiation. UT-7/GM was used as a model system, because this cell
line can differentiate into erythroid-lineage cells with EPO treatment (Komatsu
et al, Blood 89:4021, 1997). We found that EPO did not activate Stat1alpha or
Stat3 in UT-7/GM cells. Transfection experiments showed that both Stat1alpha and
Stat3 inhibited the induction by EPO of gamma-globin and erythroid-specific 5
aminolevulinate synthetase transcripts, resulting in a reduction of the
percentage of hemoglobin-positive cells. Dominant negative forms of Stat1alpha or
Stat3 promoted the EPO-induced erythroid differentiation of UT-7/GM cells, even
in the presence of granulocyte-macrophage colony-stimulating factor, although
this cytokine never induced erythroid differentiation of the parent UT-7/GM cells
with or without EPO. A cell cycle analysis showed that the constitutive
activation of Stat1alpha, but not Stat3, shortened the period of G0/G1
prolongation caused by EPO stimulation. Taken together, our data suggest that
Stat1alpha and Stat3 act as negative regulators in EPO-induced erythroid
differentiation. Specifically, Stat1alpha may activate a cell cycle-associated
gene(s), leading to the entry of cells into the cell cycle.
PMID- 9657746
TI - The induction of megakaryocyte differentiation is accompanied by selective Ser133
phosphorylation of the transcription factor CREB in both HEL cell line and
primary CD34+ cells.
AB - The addition of thrombopoietin (TPO) to HEL cells, cultured in a chemically
defined serum-free medium, induced a rapid and dose-dependent phosphorylation of
the transcription factor CREB on serine133 (PSer133), as detected by Western blot
analysis. TPO also significantly increased the transactivation of CRE-dependent
promoter, as determined in transient transfection experiments. On the other hand,
neither erythropoietin (Epo; 1 to 10 U) nor hemin (10 (-7) mol/L) were able to
significantly stimulate CREB-PSer133 or to activate CRE-promoter in HEL cells.
Although pharmacological inhibitors of protein kinase C (chelerytrine and BIM)
and protein kinase A (H-89) failed to block the TPO-mediated CREB
phosphorylation, a specific inhibitor of the mitogen-activated protein kinases
(PD98059) completely blocked the ability of TPO to stimulate CREB-PSer133.
Moreover, PD98059 significantly decreased the ability of TPO to upregulate the
surface expression of the alphaIIIbbeta3 megakaryocytic marker in HEL cells. In
parallel, primary CD34+ hematopoietic cells were seeded in liquid cultures
supplemented with 100 ng/mL of TPO and examined by immunofluorescence for the
coexpression of alphaIIIbbeta3 and CREB-PSer133 at various time points. High
levels of nuclear CREB-PSer133 were unequivocally demonstrated in alphaIIIbbeta3+
cells, including morphologically recognizable megakaryocytes. Taken together,
these data suggest that CREB plays a role in modulating the expression of genes
critical for megakaryocyte differentiation and that the TPO-mediated CREB
phosphorylation seems to be regulated via mitogen-activated protein kinases.
PMID- 9657747
TI - A novel Asn344 deletion in the core domain of coagulation factor XIII A subunit:
its effects on protein structure and function.
AB - In this study a previously undescribed 3 bp deletion, AAT1030-1032, in the factor
XIII A subunit gene, has been detected in a Thai patient. The inframe deletion
results in the translation of a factor XIII A subunit that lacks Asn344. This is
the first inframe deletion to be identified in the factor XIII A subunit gene
because six previously reported deletions have all caused frameshifts. The
deletion has been introduced into a factor XIII A subunit cDNA and the deleted
polypeptide expressed in yeast. The mRNA encoding the mutant enzyme appears to
have normal stability but the translated protein is subject to premature
degradation. In addition, the mutated enzyme exhibited very little
transglutaminase activity compared with the wild-type enzyme. Structural modeling
of the deleted enzyme suggests that the absence of Asn344 would have a potent
impact on the catalytic activity by reorienting the residues associated with the
catalytic center. Thus, the Asn344 deletion strongly confirms the significance of
the residues surrounding the catalytic center of the factor XIII A subunit.
PMID- 9657748
TI - In vivo expression of murine platelet glycoprotein Ibalpha.
AB - We have performed a systematic in vivo evaluation of gene expression for the
glycoprotein (GP) Ibalpha subunit of the murine platelet adhesion receptor, GP Ib
IX-V. This study is warranted by in vitro observations of human GP Ibalpha
expression in cells of nonhematopoietic lineage and reports of regulation of the
GP Ibalpha gene by cytokines. However, an in vivo role for a GP Ib-IX-V receptor
has not been established beyond that described for normal megakaryocyte/platelet
physiology and hemostasis. Our Northern analysis of mouse organs showed high
levels of GP Ibalpha mRNA in bone marrow with a similar expression pattern
recapitulated in mice containing a luciferase transgene under the control of the
murine GP Ibalpha promoter. Consistently high levels of luciferase activity were
observed in the two hematopoietic organs of mice, bone marrow (1,400 relative
light units/microg of protein [RLUs]) and spleen (500 RLUs). Reproducible, but
low-levels of luciferase activity were observed in heart, aorta, and lung (30 to
60 RLUs). Among circulating blood cells, the luciferase activity was exclusively
localized in platelets. No increase in GP Ibalpha mRNA or luciferase activity was
observed after treatment of mice with lipopolysaccharides (LPS) or tumor necrosis
factor-alpha (TNF-alpha). We conclude the murine GP Ibalpha promoter supports a
high level of gene expression in megakaryocytes and can express heterologous
proteins allowing an in vivo manipulation of platelet-specific proteins in the
unique environment of a blood platelet.
PMID- 9657749
TI - Mechanism and kinetics of factor VIII inactivation: study with an IgG4 monoclonal
antibody derived from a hemophilia A patient with inhibitor.
AB - The development of an immune response towards factor VIII (fVIII) remains a major
complication for hemophilia A patients receiving fVIII infusions. The design of a
specific therapy to restore unresponsiveness to fVIII has been hampered by the
diversity of the anti-fVIII antibody. Molecular analysis of the specific immune
response is therefore required. To this end, we have characterized an fVIII
specific human IgG4kappa monoclonal antibody (BO2C11) produced by a cell line
derived from the memory B-cell repertoire of a hemophilia A patient with
inhibitor. BO2C11 recognizes the C2 domain of fVIII and inhibits its binding to
both von Willebrand factor (vWF) and phospholipids. It completely inhibits the
procoagulant activity of native and activated fVIII, with a specific activity of
approximately 7,000 Bethesda units/mg. vWF reduces the rate of fVIII inactivation
by BO2C11. The antibody-fVIII association rate constant (kass approximately 7.4 x
10(5) M-1 s-1) is eightfold lower than that for vWF-fVIII association, whereas
its dissociation rate constant (kdiss < or = 1 x 10(-5) s-1) is 100-fold lower
than that for the vWF-fVIII complex, which suggests that BO2C11 almost
irreversibly neutralizes fVIII after its dissociation from vWF. BO2C11 is the
first human monoclonal anti-fVIII IgG antibody that has been isolated and allows
the study of fVIII inactivation at the molecular level.
PMID- 9657750
TI - Platelet-endothelial cell interactions during ischemia/reperfusion: the role of P
selectin.
AB - Growing evidence supports a pathophysiological role for platelets during the
manifestation of postischemic reperfusion injury; in the current study, we
investigated the nature and the molecular determinants of platelet-endothelial
cell interactions induced by ischemia/reperfusion (I/R). Platelet-endothelium and
leukocyte-endothelium interactions after 1 hour of ischemia were monitored in
vivo within mouse small intestine. By intravital fluorescence microscopy, we
observed that platelets, like leukocytes, roll along or firmly adhere to
postischemic microvascular endothelial cells. In contrast, few leukocyte
endothelial cell interactions were detected in sham-operated controls. Monoclonal
antibodies against P-selectin significantly attenuated platelet rolling and
adherence in response to I/R. To identify whether platelet or endothelial P
selectin plays the major role in mediating postischemic platelet-endothelial cell
interactions, P-selectin-deficient or wild-type platelets were transfused into
wild-type or P-selectin-deficient mice, respectively. Whereas platelets lacking P
selectin rolled along or adhered to postischemic wild-type endothelium,
interactions between wild-type platelets with mutant endothelium were nearly
absent, indicating that I/R-induced platelet-endothelium interactions are
dependent on the expression of P-selectin by endothelial cells. Concomitantly, P
selectin expression in the intestinal microvasculature was enhanced in response
to I/R, whereas no upregulation of P-selectin was observed on circulating
platelets. In summary, we provide first in vivo evidence that platelets
accumulate in the postischemic microvasculature early after reperfusion via P
selectin-ligand interactions. Platelet recruitment and subsequent activation
might play an important role in the pathogenesis of I/R injury.
PMID- 9657751
TI - High prevalence of serum cryoglobulins in multitransfused hemophilic patients
with chronic hepatitis C.
AB - The prevalence, clinical relevance, and risk factors of serum cryoglobulins in
hemophilic patients with chronic hepatitis C virus (HCV) infection are unknown.
We studied 135 consecutive hemophilic patients (median age, 31 years; range, 10
to 69 years) with chronic hepatitis C, exposed to the virus for 10 to 41 years. A
total of 67 patients were coinfected with the human immunodeficiency virus (HIV),
and 3 (2%) had signs of cirrhosis. Serum samples were tested for the presence of
cryoglobulins, hepatitis B virus (HBV) markers, including HBV-DNA by
hybridization assay, and antibody to HCV by enzyme immunoassay (EIA). Serum HCV
RNA was tested by polymerase chain reaction and typed with a hybridization
technique. Samples were also tested for antitissue antibodies, immunoglobulins,
rheumatoid factor, and C3 and C4 proteins of complement. Forty-two hemophiliacs
(31%) circulated cryoglobulins (median levels, 166 mg/L; range, 66 to 480)
predominantly type III (62%; and 29% type II). None of the patients had clinical
signs or symptoms of systemic vasculitis. Cryoglobulinemic patients had more
often serum HCV-RNA (95% v 80%, P < .05), rheumatoid factor (20% v 6%, P < .05),
higher levels of IgG (2,354 +/- 682 mg/dL v 1,928 +/- 557 mg/dL, P < .0005) and
IgM (323 +/- 226 mg/dL v 244 +/- 243 mg/dL, P < .05), and lower levels of serum
C4 (19 +/- 8 mg/dL v 24 +/- 8 mg/dL, P < .05) than patients without
cryoglobulins. The risk of producing cryoglobulins was greater for 114 patients
circulating HCV-RNA than for 21 nonviremic patients (odds ratio [OR] = 4.9, 95%
confidence interval [CI] = 1.1 to 22.0) and for the 31 patients with longer
exposure to HCV (more than 26 years) than for the 24 patients with shorter (17
years or less) exposure (OR = 4.4 95% CI = 1.1 to 18.0). In conclusion a large
number of multitransfused hemophiliacs with chronic HCV infection circulated
serum cryoglobulins but none had clinical signs or symptoms of vasculitis. The
risk of developing cryoglobulins parallels the duration of exposure to HCV.
PMID- 9657752
TI - Expression of P-selectin on hepatic endothelia and platelets promoting neutrophil
removal by liver macrophages.
AB - The role of P-selectin on polymorphonuclear leukocyte (PMN) adhesion-induced PMN
elimination in the liver is unclear. Our objectives were to show the expression
and distribution of P-selectin in rat liver, as well as to evaluate the changes
in the modulation of the expression of P-selectin and its role in the
accumulation and sequestration of PMNs. The intravenous administration of
endotoxin markedly increased the expression of P-selectin on the venous and
sinusoidal endothelial cells, as well as on the platelets trapped in the liver.
Its expression peaked at 6 hours postinjection and was associated with a rapid
increase in the aggregation and elimination of PMNs in the hepatic sinusoids.
Combined treatment with an antibody to P-selectin or with low molecular weight
heparin, a P-selectin antagonist, blocked the P-selectin, significantly reduced
the arrest of PMNs, and delayed their removal in the liver. Pretreatment with
gadolinium chloride inhibited phagocytosis of PMNs by the Kupffer cells,
decreased the expression of P-selectin, and limited the hepatic accumulation of
PMNs. Thus, P-selectin played a role in accumulation and elimination of PMNs from
the liver. Results also suggest that activated Kupffer cells can modulate the
expression of P-selectin in the liver and influence the homeostasis of PMNs in
the circulation during acute inflammation.
PMID- 9657753
TI - Binding of factor VIII to von willebrand factor is enabled by cleavage of the von
Willebrand factor propeptide and enhanced by formation of disulfide-linked
multimers.
AB - von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor
VIII binding site/subunit. Prior reports suggest that posttranslational
modifications of vWF, including formation of N-terminal intersubunit disulfide
bonds and subsequent cleavage of the propeptide, influence availability and/or
affinity of factor VIII binding sites. We found that deletion of the vWF
propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit
disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold
lower affinity than multimeric vWF in an equilibrium flow cytometry assay
(approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF
with the vWF propeptide in trans yielded multimeric vWF that displayed increased
affinity for factor VIII. Insertion of an alanine residue at the N-terminus of
the mature vWF subunit destroyed binding to factor VIII, indicating that the
native mature N-terminus is required for factor VIII binding. The requirement for
vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide
cleavage site yielding pro-vWF that was defective in factor VIII binding and (2)
correlation between efficiency of intracellular propeptide cleavage and factor
VIII binding. Furthermore, in a cell-free system, addition of the propeptide
cleaving enzyme PACE/furin enabled factor VIII binding in parallel with
propeptide cleavage. Our results indicate that high-affinity factor VIII binding
sites are located on N-terminal disulfide-linked vWF subunits from which the
propeptide has been cleaved.
PMID- 9657754
TI - Ig receptor binding protein 1 (alpha4) is associated with a rapamycin-sensitive
signal transduction in lymphocytes through direct binding to the catalytic
subunit of protein phosphatase 2A.
AB - Rapamycin is an immunosuppressant that effectively controls various immune
responses; however, its action in the signal transduction of lymphocytes has
remained largely unknown. We show here that a phosphoprotein encoded by mouse
alpha4 (malpha4) gene transmitting a signal through B-cell antigen receptor (BCR)
is associated with the catalytic subunit of protein phosphatase 2A (PP2Ac). The
middle region of alph4, consisting of 109 amino acids (94-202), associates
directly with PP2Ac, irrespective of any other accessory molecule. Rapamycin
treatment disrupts the association of PP2Ac/alpha4 in parallel with the
inhibitory effect of lymphoid cell proliferation. The effect of rapamycin was
inhibited with an excess amount of FK506 that potentially completes the binding
to FKBP. Rapamycin treatment also suppresses the phosphatase activity of cells
measured by in vitro phosphatase assay. Introduction of the malpha4 cDNA into
Jurkat cells or the increased association of PP2Ac/alpha4 by the culture with low
serum concentration confers cells with rapamycin resistance. Moreover,
glutathione S-transferase (GST)-alpha4 augments the PP2A activity upon myelin
basic protein (MBP) and histone in the in vitro assay. These results suggest that
alpha4 acts as a positive regulator of PP2A and as a new target of rapamycin in
the activation of lymphocytes.
PMID- 9657755
TI - Role for tyrosine phosphorylation and Lyn tyrosine kinase in fas receptor
mediated apoptosis in eosinophils.
AB - Fas ligand/Fas receptor molecular interactions have been implicated as having an
important function for the regulation of eosinophil apoptosis. The purpose of the
present study was to investigate biochemical events triggered by the engagement
of the Fas receptor in freshly isolated human and mouse eosinophils. Activation
of the Fas receptor on eosinophils with the agonistic anti-Fas monoclonal
antibody (MoAb) resulted in increased tyrosine phosphorylation of several
intracellular proteins. The tyrosine kinase inhibitors lavendustin A and
genistein inhibited Fas receptor-induced cell death in both human and mouse
eosinophils in vitro and prevented, at least partially, Fas receptor-mediated
resolution of eosinophilic inflammation in a mouse in vivo model of lung
eosinophilia. In addition, in freshly purified human eosinophils, lavendustin A
prevented anti-Fas MoAb-induced proteolytic cleavage of lamin B, suggesting that
tyrosine kinases may amplify the proteolytic signaling cascade within interleukin
1beta converting enzyme (ICE) family proteases. Moreover, the tyrosine kinase Lyn
was identified as being involved in Fas receptor-mediated cell death.
Collectively, these results demonstrate that tyrosine phosphorylation is an
important step in the generation of the Fas receptor-linked transmembrane death
signal in eosinophils and that Lyn participates in this pathway.
PMID- 9657756
TI - Shiga toxin type 1 activates tumor necrosis factor-alpha gene transcription and
nuclear translocation of the transcriptional activators nuclear factor-kappaB and
activator protein-1.
AB - Shiga toxins (Stxs) produced by Shigella dysenteriae 1 and Escherichia coli have
been implicated in the pathogenesis of bloody diarrhea, acute renal failure, and
neurologic abnormalities. The pathologic hallmark of Stx-mediated tissue damage
is the development of vascular lesions in which endothelial cells are swollen and
detached from underlying basement membranes. However, in vitro studies using
human vascular endothelial cells demonstrated minimal Stx-induced cytopathic
effects, unless the target cells were also incubated with the proinflammatory
cytokines tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1bta).
These cytokines have been shown to upregulate the expression of the Stx-binding
membrane glycolipid globotriaosylceramide (Gb3). We show here that purified Stx1
induces TNF secretion by a human monocytic cell line, THP-1, in a dose- and time
dependent manner. Treatment of cells with both lipopolysaccharides (LPS) and Stx1
results in augmented TNF production. Treatment with the nontoxic Gb3-binding
subunit of Stx1 or with an anti-Gb3 monoclonal antibody did not trigger TNF
production. Northern blot analyses show that Stx1 causes increased TNF-alpha
production through transcriptional activation. Increased levels of TNF-alpha mRNA
are preceded by the nuclear translocation of the transcriptional activators NF
kappaB and AP-1 and the loss of cytoplasmic IkappaB-alpha. These data are the
first to show that, in addition to direct cytotoxicity, Stxs possess cellular
signaling capabilities sufficient to induce the synthesis of cytokines that may
be necessary for target cell sensitization and the development of vascular
lesions.
PMID- 9657757
TI - Telomerase activity in Hodgkin's disease.
AB - Telomere maintenance executed by the action of telomerase seems to be a
prerequisite for immortalization. Telomerase is found in most cell lines and
malignant tumors. A telomerase-independent mechanism for telomere maintenance in
Hodgkin's disease has been proposed in the absence of detectable telomerase
activity. In this study, telomerase activity was detected in 31 of 77 Hodgkin's
disease samples and a strong correlation between eosinophilia and absence of
detectable telomerase activity was found. Purified eosinophils and specifically
eosinophil-derived neurotoxin and eosinophilic cationic protein, both
ribonucleases, were found to degrade telomerase. Purified neutrophils also
exhibited weak telomerase degradative activity. Reanalysis of previously
telomerase-negative Hodgkin's disease samples with eosinophilia using
ribonuclease inhibitors resulted in the detection of telomerase activity.
Ribonuclease-containing cells in vivo thus have a considerable impact on the
detectability of telomerase. In Hodgkin's disease samples without eosinophilia,
24 of 27 exhibited telomerase activity at decreased levels compared with non
Hodgkin's lymphomas and at increased levels compared with reactive nodes
indicative of a telomerase positive tumor component in Hodgkin's disease.
Telomerase positivity of the Hodgkin's and Reed-Sternberg cells in vivo was also
supported by high levels of telomerase expression in Hodgkin's disease cell
lines. Based on our data, Hodgkin's lymphomas are potential targets for
antitelomerase therapy.
PMID- 9657758
TI - Multiplex reverse transcription-polymerase chain reaction for simultaneous
screening of 29 translocations and chromosomal aberrations in acute leukemia.
AB - We have developed a multiplex reverse transcription-polymerase chain reaction (RT
PCR) reaction, which enables us to detect 29 translocations/chromosomal
aberrations in patients with acute lymphoid leukemia (ALL) and acute myeloid
leukemia (AML). Through the construction and optimization of specific primers for
each translocation, we have been able to reduce the set-up to 8 parallel
multiplex PCR reactions, thus greatly decreasing the amount of work and reagents.
We show the value of our set-up in a retrospective analysis on cryopreserved
material from 102 AML and 62 ALL patients. The multiplex RT-PCR detected a hybrid
mRNA resulting from a structural chromosomal aberration in 45 of 102 (44%) of the
AML and in 28 of 62 (45%) of the pediatric ALL cases. Importantly, in 33% of AML
and in 47% of the ALL cases with cytogenetic data, submicroscopic chromosomal
aberrations or masked translocations were shown that were not detected in the
cytogenetic analysis either for structural reasons or because of an insufficient
number of metaphases obtained. This multiplex RT-PCR system, which can handle up
to 10 patients with a response time of 2 working days, is thus an important tool
that complements cytogenetic analysis in the up-front screening of acute leukemia
patients and should provide a rapid and efficient characterization of leukemia
cells, even in situations with sparse patient material.
PMID- 9657759
TI - Malignant progenitors from patients with acute myelogenous leukemia are sensitive
to a diphtheria toxin-granulocyte-macrophage colony-stimulating factor fusion
protein.
AB - We have previously demonstrated that human granulocyte-macrophage colony
stimulating factor (GM-CSF) fused to a truncated diphtheria toxin (DT388-GMCSF)
kills acute myelogenous leukemia (AML) cell lines bearing the GM-CSF receptor. We
now report that exposure of malignant cells from 50 different patients with AML
for 48 hours in culture to DT388-GMCSF reduces by a median of 1.6 logs (range, 0
to 3.7 logs) the number of leukemic cells capable of forming colonies in
semisolid media (leukemic colony-forming cells [CFU-L]) with a median IC50 of 3 x
10(-12) mol/L (range, 5 to >4,000 x 10(-12) mol/L). Furthermore, the cell kill is
dependent on the presence of high-affinity GM-CSF receptors on leukemic blasts,
because CFU-L from 27 of 28 AML samples expressing > or = 35 GM-CSF receptors per
cell were inhibited by the toxin, whereas the colony growth from all 4 leukemic
samples (2 AML, 1 acute lymphoblastic leukemia [ALL], and 1 prolymphocytic
leukemia [PLL]) that had less than 35 receptors per cell was unaffected by the
drug. Sensitivity of CFU-L to DT388-GMCSF was seen regardless of the clinical
responsiveness of the patient's leukemia to standard chemotherapy agents. In
contrast, clonogenic cells from normal bone marrow formed colonies at near
control numbers after exposure to much higher toxin concentrations (4 x 10(-9)
mol/L) than those required to kill CFU-L from most patients. Thus, leukemic
progenitors isolated directly from the peripheral blood of most AML patients show
the same sensitivity to DT388-GMCSF as previously demonstrated for AML cell
lines. Under the same conditions of exposure, normal hematopoietic progenitors
are relatively unaffected by DT388-GMCSF, suggesting its potential as a
therapeutic agent in AML.
PMID- 9657760
TI - The reliability and specificity of c-kit for the diagnosis of acute myeloid
leukemias and undifferentiated leukemias. The European Group for the
Immunological Classification of Leukemias (EGIL).
AB - We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de
novo acute leukemia cases, diagnosed in five single European centers. All cases
were well characterized as to the morphologic, cytochemical, and immunologic
features, according to the European Group for the Immunological Classification of
Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819
acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4
undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of
the French-American-British (FAB) subtype, one third of BAL, all four AUL, but
only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified
as: T-cell lineage (two thirds), mainly pro-T-ALL or T-I, and B lineage (one
third); cells from 62% of these ALL cases coexpressed other myeloid markers
(CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML
or ALL cases according to age being similar in the adult and pediatric groups.
Our findings demonstrate that c-kit is a reliable and specific marker to detect
leukemia cells committed to the myeloid lineage, and therefore should be included
in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid
commitment of the blasts. c-kit expression should score higher, at least one
point, in the system currently applied to the diagnosis of BAL, as its myeloid
specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c
kit identifies a subgroup of cases, which may correspond to leukemias either
arising from early prothymocytes and/or early hematopoietic cells, both able to
differentiate to the lymphoid and myeloid pathways.
PMID- 9657761
TI - Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the
EBNA-1 gene.
AB - We have described 5 major subtypes of Epstein-Barr virus (EBV) based on
variations in EBNA-1 sequences. These include P-ala (identical to the prototype
B95.8 virus), P-thr, V-pro, V-leu, and V-val. Normal individuals often carry
multiple EBV subtypes, the most common being P-ala, whereas EBV-associated tumors
examined to date always contain a single subtype, which only on rare occasion is
P-ala. The primary hypotheses that these observations generate are as follows:
(1) Each of these EBV subtypes are naturally occurring, and in normal individuals
the multiplicity of subtypes results from multiple infections. (2) EBV subtypes
in normal individuals are generated in vivo from a single infecting virus subtype
by mutations in EBNA-1. The second hypothesis essentially excludes the
possibilities that the nonrandom association of certain subtypes with lymphomas
is secondary to the geographic distribution of EBV subtypes and, if proven
correct, could provide strong support for a direct role of EBV in tumorigenesis.
In this report, we provide evidence for the latter hypothesis. We show that the P
ala EBV subtype present in most nasal lymphomas undergoes and accumulates
multiple mutations consistent with the generation of variant species of EBNA-1 in
vivo. This phenomenon is similar to the generation of quasispecies in RNA viruses
and is the first description of in vivo generation of subtypes in DNA viruses. In
RNA-based viruses, including human immunodeficiency virus and hepatitis C virus,
the emergence of quasispecies is linked to replication infidelity and
significantly influences disease processes through its effect on viral tropism,
the emergence of viruses resistant to the host defenses or to therapy, and
pathogenicity. The present data thus raise important questions relating to the
mechanisms whereby these mutations are generated in EBV and their relevance to
the pathogenicity of EBV-associated lymphomas.
PMID- 9657762
TI - Impaired granulocytic differentiation in vitro in hematopoietic cells lacking
retinoic acid receptors alpha1 and gamma.
AB - Transcripts for the retinoic acid receptors (RARs) alpha1, alpha2, gamma1, and
gamma2 were found in the granulocytic lineage (Gr-1+ cells) through
semiquantitative polymerase chain reaction (PCR) analysis. The screening of
single cell cDNA libraries derived from hematopoietic progenitors also showed the
presence of RARalpha and, to a lesser extent, RARgamma transcripts in committed
granulocyte (colony-forming unit-granulocyte [CFU-G]) or granulocyte-macrophage
(CFU-GM) colony-forming cells. The contribution of RARalpha1 and gamma to
hematopoietic cell differentiation was therefore investigated in mice bearing
targeted disruption of either one or both of these loci. Because RARgamma and
RARalpha1gamma compound null mutants die shortly after birth, bone marrow cells
were collected from fetuses at 18.5 days postcoitum (dpc) and evaluated for
growth and differentiation in culture in the presence of Steel factor (SF),
interleukin-3 (IL-3), and erythropoietin (Epo). The frequency of colony-forming
cells from bone marrow populations derived from RARalpha1/gamma double null mice
was not significantly different from that of RARgamma or RARalpha1 single nulls
or from wild-type controls. In addition, the distribution of erythroid,
granulocyte, and macrophage colonies was comparable between hematopoietic cells
from all groups, suggesting that lineage commitment was not affected by the lack
of RARalpha1 and/or RARgamma. Colony cells were then harvested individually and
evaluated by morphologic criteria. While terminal granulocyte differentiation was
evident in wild-type cells and colonies from either single null mutant, colonies
derived from RARalpha1-/-gamma-/- bone marrow populations were blocked at the
myelocyte and, to a lesser extent, at the metamyelocyte stages, whereas erythroid
and macrophage differentiation was not affected. Together, these results indicate
that both RARalpha1 and gamma are required for terminal maturation in the
granulocytic lineage in vitro, but appear to be dispensable for the early stages
of hematopoietic cell development. Our results raise the possibility that in
acute promyelocytic leukemia (APL), the RARalpha fusion proteins cause
differentiation arrest at a stage when further maturation requires not only
RARalpha, but also RARgamma. Finally, bone marrow cells appear to differentiate
normally in vivo, suggesting an effective compensation mechanism in the
RARalpha1/gamma double null mice.
PMID- 9657763
TI - Lack of clinically significant contact system activation during platelet
concentrate filtration by leukocyte removal filters.
AB - When blood (plasma) contacts certain foreign surfaces, factor XII can activate
and trigger a series of reactions leading to cleavage of kininogens with
subsequent release of bradykinin. In this study, we investigated two different
widely used leukocyte removal filters, Pall PXL8K (A) and Asahi PLS-5A (B), to
test whether clinically significant contact activation occurred during
leukodepletion of platelet-rich plasma (PRP). Kininogens were measured by
particle concentration fluorescence immunoassay (PCFIA), which can detect
cleavage of high and low molecular weight kininogens (HK and LK), the parent
molecules of bradykinin, to determine if contact activation had occurred. A
slight, nonsignificant decrease in HK and LK was observed with filter A after the
first 5 mL was filtered that returned to prefiltration levels by the end of the
filtration. Specific TotK (the combined measurement of HK and LK heavy chains
divided by plasma protein concentration) showed a small, significant decrease
with filter A after the first 5 mL of platelet concentrates was filtered that
returned to prefiltration levels by the end of the filtration. There were no
significant increases or decreases in the cleaved kininogen index (CKI), an index
of HK proteolytic activation or HK and LK destruction (with release of
bradykinin). These data suggest that small amounts of both HK and LK initially
adsorb to filter A and then desorb, primarily intact. These data also indicate
that no significant contact activation, as measured by PCFIA, occurs during
leukodepletion of platelet concentrates with either filter A or B.
PMID- 9657764
TI - Regulation and processing of a precursor form of eosinophil granule major basic
protein (ProMBP) in differentiating eosinophils.
AB - The cDNA for eosinophil granule major basic protein (MBP) encodes a
prepromolecule with a total length of 222 amino acids (preproMBP). PreproMBP
includes a secretory leader of 15 amino acids, an acidic propiece of 90 amino
acids, and a basic MBP portion of 117 amino acids. The function of the propiece,
which has a predicted pI of 3.9, is unknown, but it gives proMBP an overall
acidic charge. Because proMBP is not found in mature eosinophils, we analyzed
eosinophil differentiation in interleukin-5 (IL-5)-stimulated umbilical cord stem
cells cultured for 24 days. By immunofluorescence, proMBP appeared by day 6 and
peaked on day 18, whereas MBP was prominent at days 12 to 24. By day 6, Western
blots detected heterogeneous glycosylated 33-kD proMBP; its peak expression
occurred on day 12. Western blots showed sequential processing of 33-kD proMBP to
an 18-kD intermediate form and finally to 14-kD MBP. By dual label immunoelectron
microscopy, proMBP was localized primarily to large uncondensed eosinophil
granules, whereas MBP was localized to granules containing a condensed central
area. Thus, proMBP is likely expressed and processed as the granule condenses in
a multistep process to 14-kD MBP in differentiating eosinophils.
PMID- 9657765
TI - The iron chelator L1 potentiates oxidative DNA damage in iron-loaded liver cells.
AB - Iron-mediated carcinogenesis is thought to occur through the generation of oxygen
radicals. Iron chelators are used in attempts to prevent the long term
consequences of iron overload. In particular, 1,2-dimethyl-3-hydroxypyrid-4-one
(L1), has shown promise as an effective chelator. Using an established
hepatocellular model of iron overload, we studied the generation of iron
catalyzed oxidative DNA damage and the influence of iron chelators, including L1,
on such damage. Iron loading of HepG2 cells was found to greatly exacerbate
hydrogen peroxide-mediated DNA damage. Desferrithiocin was protective against
iron/hydrogen peroxide-induced DNA damage; deferoxamine had no effect. In
contrast, L1 exposure markedly potentiated hydrogen peroxide-mediated oxidative
DNA damage in iron-loaded liver cells. However, when exposure to L1 was
maintained during incubation with hydrogen peroxide, L1 exerted a protective
effect. We interpret this as indicating that L1's potential toxicity is highly
dependent on the L1:iron ratio. In vitro studies examining iron-mediated
ascorbate oxidation in the presence of L1 showed that an L1:iron ratio must be at
least 3 to 1 for L1 to inhibit the generation of free radicals; at lower
concentrations of L1 increased oxygen radical generation occurs. In the clinical
setting, such potentiation of iron-catalyzed oxidative DNA damage at low L1:iron
ratios may lead to long-term toxicities that might preclude administration of L1
as an iron chelator. Whether this implication in fact extends to the in vivo
situation will have to be verified in animal studies.
PMID- 9657766
TI - Molecular defects of the RHCE gene in Rh-deficient individuals of the amorph
type.
AB - The deficiency of Rh proteins on the red blood cells from individuals of the
Rhnull amorph type may be the result of homozygosity for a silent allele at the
RH locus. This phenotype is also associated with the lack or reduced expression
of glycoproteins (Rh50, CD47, LW, and glycophorin B), which interact with Rh
polypeptides to form the multisubunit Rh membrane complex. In this study, we
describe two molecular alterations affecting the RHCE gene in two unrelated
Rhnull amorph individuals bearing Rh50 and CD47 normal transcripts. The first
type of mutation, located at the donor splice-site in intron 4, induced the
activation of two cryptic splice-sites within this intron and one such site in
exon 4 that all generated aberrant transcripts. The second type of mutation
affected the coding region and introduced a frameshift and a premature stop codon
resulting in a shorter predicted protein (398 v 417 residues), including a
completely different C-terminus of 76 amino acids. This suggests that protein
folding and/or protein-protein interaction mediated by the C-terminal domain of
the Rh proteins may play a role in the routing and/or stability of the Rh
membrane complex.
PMID- 9657767
TI - Six previously undescribed pyruvate kinase mutations causing enzyme deficiency.
AB - Erythrocyte pyruvate kinase deficiency is the most common cause of hereditary
nonspherocytic hemolytic anemia. We present 6 previously undescribed mutations of
the PKLR gene associated with enzyme deficiency located at cDNA nt 476 G-->T
(159Gly-->Val), 884 C-->T (295Ala-->Val), 943 G-->A (315Glu-->Lys), 1022 G-->A
(341Gly-->Asp), 1511 G-->T (504Arg-->Leu), and 1528 C-->T (510Arg-->Ter). Two of
these mutations are near the substrate binding site: the 315Glu-->Lys (943A)
mutation may be involved in Mg2+ binding and 159Gly-->Val (476T) mutation has a
possible effect on ADP binding. Four of six mutations produce deduced changes in
the shape of the molecule. Two of these mutations, 504Arg-->Leu (1511T) and
510Arg-->Ter (1528T), are located at the interface of domains A and C. One of
them (510Arg-->Ter) is a deletion of the C-terminal residues affecting the
integrity of the protein. The 504Arg-->Leu mutation eliminates a stabilizing
interaction between domains A and C. Changes in amino acid 341(nt 1022) from Gly
to Asp cause local perturbations. The mutation 295Ala-->Val (884T) might affect
the way pyruvate kinase interacts with other molecules. We review previously
described mutations and conclude that there is not yet sufficient data to allow
us to draw conclusions regarding genotype/phenotype relationship.
PMID- 9657768
TI - Full activity from human beta-globin locus control region transgenes requires
5'HS1, distal beta-globin promoter, and 3' beta-globin sequences.
AB - The locus control region (LCR) activates high-level human beta-globin transgene
expression. LCR cassettes composed of 5'HS2-4 linked to the 815 bp beta-globin
proximal promoter do not express fully. Here, we show that LCR (5'HS2-4) beta
globin transgenes that also contain either 5'HS1 or the distal promoter fail to
express fully in single- and low-copy transgenic mice. In contrast, full
expression is obtained in the presence of both 5'HS1 and the distal promoter.
Nine factor binding sites were identified in 5'HS1, using in vitro DNaseI
footprint and gel retardation assays, and these include a strong Sp1/Sp3 site,
four GATA-1 sites, and two sites that encompass an ACTAAC motif. LCR (5'HS1-4)
beta-globin transgene constructs with the distal promoter deleted or replaced by
spacer DNA show that specific distal promoter sequences are required for full
expression. An LCR (5'HS1-4) transgene construct with truncated downstream beta
globin gene sequences indicates that 3' sequences also play an important role.
These results show that full expression of the beta-globin gene directed by the
LCR requires 5'HS1, the distal beta-globin promoter, and 3' sequences, and has
implications for gene therapy construct design and models of LCR activation.
PMID- 9657769
TI - Rhnull disease: the amorph type results from a novel double mutation in RhCe gene
on D-negative background.
AB - Rhnull disease, which includes the amorph and regulator types, is a rare genetic
disorder characterized by stomatocytosis and chronic hemolytic anemia. We studied
here a German family transmitting a putative amorph Rhnull disease gene and
identified a rare mutation causing the loss-of-function phenotype. We analyzed
the genomic and transcript structure of RH30, RH50, and CD47, the three loci
thought to be most critical for expression of the Rh complex in the red blood
cell membrane. We showed that in this family the Rh50 and CD47 transcripts were
normal in primary sequence. However, the RH30 locus contained an unusual double
mutation in exon 7 of the RhCe gene, in addition to a deletion of the RhD gene.
The mutation targeted two adjacent codons in multiple arrangements probably via
the mechanism of microgene conversion. One scheme entails a noncontiguous
deletion of two nucleotides, [ATT(Ile322)-->AT] and [CAC(His323)-->CC], whereas
the other involves a T-->C transition [ATT(Ile322)--> ATC] and a dinucleotide
deletion [CAC(His323)-->C]. They caused the same shift in open reading frame
predicted to encode a shortened protein with 398 amino acids. The loss of two
transmembrane domains and gain of a new C-terminal sequence are likely to alter
the protein conformation and impair the Rh complex assembly. Our findings
establish the molecular identity of an amorph Rhnull disease gene, showing that
Rh30 and Rh50 are both essential for the functioning of the Rh structures as a
multisubunit complex in the plasma membrane.
PMID- 9657770
TI - Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce
breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a
potential purging method for autologous transplantation.
AB - Ad.CMV-CD is a replication incompetent adenoviral vector carrying a
cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD)
gene. The CD transcription unit in this vector catalyzes the deamination of the
nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic
drug 5-fluorouracil (5-FU). This adenoviral vector prodrug activation system has
been proposed for use in selectively sensitizing breast cancer cells, which may
contaminate collections of autologous stem cells products from breast cancer
patients, to the toxic effects of 5-FC, without damaging the reconstitutive
capability of the normal hematopoietic cells. This system could conceivably kill
even the nondividing breast cancer cells, because the levels of 5-FU generated by
this system are 10 to 30 times that associated with systemic administration of 5
FU. The incorporation of 5-FU into mRNA at these high levels is sufficient to
disrupt mRNA processing and protein synthesis so that even nondividing cells die
of protein starvation. To test if the CD adenoviral vector sensitizes breast
cancer cells to 5-FC, we exposed primary explants of normal human mammary
epithelial cells (HMECs) and the established breast cancer cell (BCC) lines MCF-7
and MDA-MB-453 to the Ad.CMV-CD for 90 minutes. This produced a 100-fold
sensitization of these epithelial cells to the effects of 48 hours of exposure to
5-FC. We next tested the selectivity of this system for BCC. When peripheral
blood mononuclear cells (PBMCs), collected from cancer patients during the
recovery phase from conventional dose chemotherapy-induced myelosuppression, were
exposed to the Ad.CMV-CD for 90 minutes in serum-free conditions, little or no
detectable conversion of 5-FC into 5-FU was seen even after 48 hours of exposure
to high doses of 5-FC. In contrast, 70% of 5-FC was converted into the cytotoxic
agent 5-FU when MCF-7 breast cancer cells (BCCs) were exposed to the same Ad.CMV
CD vector followed by 5-FC for 48 hours. All of the BCC lines tested were shown
to be sensitive to infection by adenoviral vectors when exposed to a recombinant
adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV
betagal). In contrast, less than 1% of the CD34-selected cells and their more
immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were
positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence
activated cell sorting (FACS) analysis, when exposed to the adenoviral vector
under conditions that did not commit the early hematopoietic precursor cells to
maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed
for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater
than 1 million fold reduction in the number of BCCs, as measured by colony
limiting dilution assays, was observed. To test if the conditions were damaging
for the hematopoietic reconstituting cells, marrow cells collected from 5-FU
treated male donor mice were incubated with the cytosine deaminase adenoviral
vector and then exposed to 5-FC either for 4 days in vitro before transplantation
or for 14 days immediately after transplantation in vivo. There was no
significant decrease in the reconstituting capability of the male marrow cells,
as measured by their persistence in female irradiated recipients for up to 6
months after transplantation. These observations suggest that adenovirus-mediated
gene transfer of the Escherichia coli cytosine deaminase gene followed by
exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively
reduce the level of contaminating BCCs in collections of hematopoietic cells used
for autografts in breast cancer patients.
PMID- 9657771
TI - Detection of microchimerism after allogeneic blood transfusion using nested
polymerase chain reaction amplification with sequence-specific primers (PCR-SSP):
a cautionary tale.
AB - In bone marrow transplantation, the detection of chimerism is an important
adjunct to the repertoire of tests available for determining acceptance of the
graft. In solid organ transplantation, there is currently intense interest in the
role that chimerism plays in both short- and long-term host reactivity to the
graft. Allogeneic blood transfusion has been associated with a subtle
immunosuppressive effect in renal transplantation and chimerism is implicated as
a possible mechanism for this effect. To assess the survival of allogeneic cells
after blood transfusion or transplantation, we have developed a technique based
on molecular typing for HLA class II alleles, which enables the detection of
donor-derived cells in patients receiving blood transfusions. While developing
this technology, we investigated why we and others observe false amplification.
Sequencing of false products has shown that they arise from amplification of both
pseudogenes and non-pseudogenes present in the DNA under test. Elucidation of
this phenomenon allows the amplification of these false products to be predicted
in any given combination and hence avoided by the judicious selection of primers.
Validation has been achieved by following donor alleles after transfusion of
blood containing defined numbers of leukocytes expressing selected mismatched
antigens.
PMID- 9657772
TI - Role of class-II major histocompatibility complex (MHC)-antigen-positive donor
leukocytes in transfusion-induced alloimmunization to donor class-I MHC antigens.
AB - It has been shown that peripheral-blood mononuclear leukocytes (MNL) are
responsible for transfusion-induced alloimmunization to donor major
histocompatability complex (MHC) antigens. However, it is not known which subset
of MNL is responsible for this immune response. Because elimination of class-II
MHC antigen-positive passenger leukocytes effectively prolongs the survival of
allografts, it has been hypothesized that class-II positive MNL are responsible
for immunizing transfusion recipients to donor MHC antigens. To test this
hypothesis, two different approaches were used. First, we compared the
alloantigenicity of BALB/c mice (H-2(d)) peripheral blood MNL before and after
depletion of class-II positive cells. CBA mice (H-2(k)) were used as transfusion
recipients. Antibody development to donor class-I H-2 antigens was determined by
flow cytometry and enzyme-linked immunoassay. After four weekly transfusions of
MNL depleted for class-II positive cells, only 25% of recipient mice developed
antibodies to donor H-2(d) antigens. In contrast, all mice transfused with
control MNL became immunized. Second, we studied the alloantigenicity of
peripheral MNL from C57BL/6 mice (H-2(b)) with homozygous deficiency of class-II
MHC molecules in H-2 disparate recipient mice. After transfusions with class-II
MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and 25% of CBA-recipient
mice developed antibodies to donor H-2(b) antigen. All control recipient mice
were immunized. The antibody activities of the controls were also higher than
those in the treatment group who became immunized. Thus, our study shows that
class-II MHC antigen-positive MNL play a significant role in transfusion-induced
alloimmunization to donor class-I MHC antigens. The results also support the
hypothesis that direct antigen presentation by donor class-II positive MNL to the
immune system of transfusion recipients is critical for the initiation of humoral
immune response to donor MHC antigens.
PMID- 9657773
TI - Prognostic value of cytogenetics and multidrug resistance (MDR1) in elderly
patients with acute myeloid leukemia.
PMID- 9657774
TI - Biological features of acute myeloid leukemia in the elderly.
PMID- 9657775
TI - A case of Wiskott-Aldrich syndrome with dual mutations in exon 10 of the WASP
gene: an additional de novo one-base insertion, which restores frame shift due to
an inherent one-base deletion, detected in the major population of the patient's
peripheral blood lymphocytes.
PMID- 9657776
TI - c-kit activating mutations and mast cell proliferation in human leukemia.
PMID- 9657777
TI - The role of factor XII in contact system activation.
PMID- 9657778
TI - The prothrombin G20210A mutation and factor V Leiden mutation in patients with
cerebrovascular disease.
PMID- 9657779
TI - Pulmonary embolism. Hospitals should develop their own strategies for diagnosis
and management.
PMID- 9657780
TI - Vitamin B-6: food or medicine? The rules--and the politics--are different.
PMID- 9657781
TI - Improving the management of soft tissue sarcoma. Diagnosis and treatment should
be given in specialist centres.
PMID- 9657782
TI - Bournewood: an indefensible gap in mental health law. Capacity is set to become a
major clinicolegal issue.
PMID- 9657783
TI - Quality to the fore in health policy--at last. But the NHS mustn't encourage
quality improvement with punitive approaches.
PMID- 9657784
TI - Randomised controlled trial of laparoscopic versus open mesh repair for inguinal
hernia: outcome and cost.
AB - OBJECTIVE: To compare tension-free open mesh hernioplasty under local anaesthetic
with transabdominal preperitoneal laparoscopic hernia repair under general
anaesthetic. DESIGN: A randomised controlled trial of 403 patients with inguinal
hernias. SETTING: Two acute general hospitals in London between May 1995 and
December 1996. SUBJECTS: 400 patients with a diagnosis of groin hernia, 200 in
each group. MAIN OUTCOME MEASURES: Time until discharge, postoperative pain, and
complications; patients' perceived health (SF-36), duration of convalescence, and
patients' satisfaction with surgery; and health service costs. RESULTS: More
patients in the open group (96%) than in the laparoscopic group (89%) were
discharged on the same day as the operation (chi2 = 6.7; 1 df; P=0.01). Although
pain scores were lower in the open group while the effect of the local
anaesthetic persisted (proportional odds ratio at 2 hours 3.5 (2.3 to 5.1)),
scores after open repair were significantly higher for each day of the first week
(0.5 (0.3 to 0.7) on day 7) and during the second week (0.7 (0.5 to 0.9)). At 1
month there was a greater improvement (or less deterioration) in mean SF-36
scores over baseline in the laparoscopic group compared with the open group on
seven of eight dimensions, reaching significance on five. For every activity
considered the median time until return to normal was significantly shorter for
the laparoscopic group. Patients randomised to laparoscopic repair were more
satisfied with surgery at 1 month and 3 months after surgery. The mean cost per
patient of laparoscopic repair was 335 pounds (95% confidence interval 228 pounds
to 441 pounds) more than the cost of open repair. CONCLUSION: This study confirms
that laparoscopic hernia repair has considerable short term clinical advantages
after discharge compared with open mesh hernioplasty, although it was more
expensive.
PMID- 9657785
TI - Demographic and epidemiological determinants of healthcare costs in Netherlands:
cost of illness study.
AB - OBJECTIVES: To determine the demands on healthcare resources caused by different
types of illnesses and variation with age and sex. DESIGN: Information on
healthcare use was obtained from all 22 healthcare sectors in the Netherlands.
Most important sectors (hospitals, nursing homes, inpatient psychiatric care,
institutions for mentally disabled people) have national registries. Total
expenditures for each sector were subdivided into 21 age groups, sex, and 34
diagnostic groups. SETTING: Netherlands, 1994. MAIN OUTCOME MEASURES: Proportion
of healthcare budget spent on each category of disease and cost of health care
per person at various ages. RESULTS: After the first year of life, costs per
person for children were lowest. Costs rose slowly throughout adult life and
increased exponentially from age 50 onwards till the oldest age group (> or =
95). The top five areas of healthcare costs were mental retardation,
musculoskeletal disease (predominantly joint disease and dorsopathy), dementia, a
heterogeneous group of other mental disorders, and ill defined conditions.
Stroke, all cancers combined, and coronary heart disease ranked 7, 8, and 10,
respectively. CONCLUSIONS: The main determinants of healthcare use in the
Netherlands are old age and disabling conditions, particularly mental disability.
A large share of the healthcare budget is spent on long term nursing care, and
this cost will inevitably increase further in an ageing population. Non-specific
cost containment measures may endanger the quality of care for old and mentally
disabled people.
PMID- 9657786
TI - Poverty, unemployment, and common mental disorders: population based cohort
study.
AB - OBJECTIVE: To determine whether poverty and unemployment increase the likelihood
of or delay recovery from common mental disorders, and whether these associations
could be explained by subjective financial strain. DESIGN: Prospective cohort
study. SETTING: England, Wales, and Scotland. SUBJECTS: 7726 adults aged 16-75
living in private households. MAIN OUTCOME MEASURES: Common mental disorders were
assessed using the general health questionnaire, a self assessed measure of
psychiatric morbidity. RESULTS: Poverty and unemployment (odds ratio 1.86, 95%
confidence interval 1.18 to 2.94) were associated with the maintenance but not
onset of episodes of common mental disorders. Associations between poverty and
employment and maintenance of common mental disorders, however, were much smaller
than those of cross sectional studies. Financial strain at baseline was
independently associated with both onset (1.57, 1.19 to 2.07) and maintenance
(1.86, 1.36 to 2.53) even after adjusting for objective indices of standard of
living. CONCLUSIONS: Poverty and unemployment increased the duration of episodes
of common mental disorders but not the likelihood of their onset. Financial
strain was a better predictor of future psychiatric morbidity than either of
these more objective risk factors though the nature of this risk factor and its
relation with poverty and unemployment remain unclear.
PMID- 9657787
TI - Underreporting of suspected adverse drug reactions to newly marketed ("black
triangle") drugs in general practice: observational study.
PMID- 9657789
TI - Alternative definitions
PMID- 9657790
TI - Words that count
PMID- 9657788
TI - Neglect of growth and development in the clinical monitoring of children and
teenagers with inflammatory bowel disease: review of case records.
PMID- 9657791
TI - From collaboration to commissioning: developing relationships between primary
health and social services.
PMID- 9657792
TI - Primary care: core values developing primary care: gatekeeping, commissioning,
and managed care.
PMID- 9657794
TI - The new NHS: national health service Act
PMID- 9657793
TI - Sexually transmitted infections.
PMID- 9657795
TI - Deliberate self harm in Sri Lanka: an overlooked tragedy in the developing world.
PMID- 9657796
TI - Managing demand for secondary care services: the changing context.
PMID- 9657797
TI - Getting research findings into practice. When to act on the evidence.
PMID- 9657799
TI - Golden age of surgery
PMID- 9657798
TI - Today's dogma may be tomorrow's joke
PMID- 9657800
TI - Impact of surgery for stress incontinence on morbidity. Effects of confounding
variables on outcomes of incontinence surgery must be considered.
PMID- 9657801
TI - Risk factors for winter outbreak of acute diarrhoea in France. Winter outbreaks
of diarrhoea occur in United Kingdom too.
PMID- 9657802
TI - Physical dependence on zopiclone. Prescribing this drug to addicts may give rise
to iatrogenic drug misuse.
PMID- 9657803
TI - Doctors need to know more about advance directives.
PMID- 9657804
TI - Rescue thrombolysis may work even though primary thrombolysis has failed.
PMID- 9657805
TI - Quality of life assessments may help some patients.
PMID- 9657806
TI - Integrated care pathways increase use of guidelines.
PMID- 9657807
TI - Lumbar puncture should not be delayed in subarachnoid haemorrhage.
PMID- 9657808
TI - Doctors must understand terminology used to describe psychological therapies.
PMID- 9657809
TI - Improving management of diabetes in residential and nursing homes. "Home clinic"
facilitates communication with carers.
PMID- 9657810
TI - Discrimination against gay and lesbian doctors goes against GMC's guidance.
PMID- 9657811
TI - Levonorgestrel intrauterine device can be left in place for five years.
PMID- 9657812
TI - Trevor lloyd davies
PMID- 9657813
TI - Shadow health team calls for GP ballot
PMID- 9657814
TI - Catastrophic cat care
PMID- 9657815
TI - Plus ca change..
PMID- 9657816
TI - Ceremonial haemoglobinuria
PMID- 9657818
TI - Most of healthcare budget is spent on care not cure
PMID- 9657817
TI - Recovery is quicker after laparoscopic hernia repairbut there is a cost
PMID- 9657820
TI - GPs tend to report only serious reactions to new drugs
PMID- 9657819
TI - Financial strain has a major impact on mental health
PMID- 9657822
TI - Collaboration between primary care and social services can be improved
PMID- 9657821
TI - Children with inflammatory bowel disease fail to have their growth or sexual
development recorded
PMID- 9657823
TI - Prediction of partitioning properties for benzaldehydes by various molecular
descriptors.
PMID- 9657824
TI - Development of an analytical method for the determination of congener specific
PCBs in selected polymeric packaging materials.
PMID- 9657825
TI - Optimization of enzymatic chlorine removal from Kraft pulp.
PMID- 9657826
TI - Changes in selected indicators of liver impairment after repeated administration
of mono- and polybromobenzenes in mice.
PMID- 9657827
TI - Cadmium chloride prevents the rise in rat brown adipose tissue mitochondrial
respiration in response to acute cold stress.
PMID- 9657828
TI - Growth responses of Indian mustard [Brassica juncea (L.) Czern.] and its
phytoextraction of lead from a contaminated soil.
PMID- 9657829
TI - Growth responses of radish plants to soil cadmium and lead contamination.
PMID- 9657830
TI - Sex specific interactions between Cd and Zn in three beetle species (Insecta,
Coleoptera).
PMID- 9657831
TI - Geochemistry of mercury in sediments of a sub-tropical coastal lagoon, Sepetiba
Bay, southeastern Brazil.
PMID- 9657832
TI - Copper bioaccumulation and depuration by red swamp crayfish, Procambarus clarkii.
PMID- 9657833
TI - Hydrocarbon contamination in the Canary Islands. II. Intertidal limpet Patella
ulyssiponensis aspera.
PMID- 9657834
TI - Hydrocarbon and organochlorine residue concentrations in sediments from Bay of
Chetumal, Mexico.
PMID- 9657835
TI - Effects of exposure to contaminated sediments on the parasite fauna of American
plaice (Hippoglossoides platessoides).
PMID- 9657836
TI - Effects on tropical fish of soil sediments from Kafue river, Zambia.
PMID- 9657837
TI - Sensitivity of ten aquatic species to long-term crude oil exposure.
PMID- 9657838
TI - Effect of pentachlorophenol pollution towards microalgae and microbial activities
in soil from a former timber processing facility.
PMID- 9657839
TI - Acute toxicity of ammonia to Ceriodaphnia dubia and a procedure to improve
control survival.
PMID- 9657840
TI - Acute and chronic effects of indium chloride (InCl3) on tilapia (Oreochromis
mossambicus) larvae.
PMID- 9657841
TI - Acute and chronic effects of antimony chloride (SbCl3) on tilapia (Oreochromis
mossambicus) larvae.
PMID- 9657842
TI - Effect of methyl parathion-treated prey (Brachionus calyciflorus) on the
population growth of the predator Asplanchna sieboldi (Rotifera).
PMID- 9657843
TI - Prions and the prion disorders.
AB - One of us remembers sitting in a high school biology class in 1977 being taught
about scrapie, a naturally occurring disorder of sheep. The teacher had no
particular interest in agriculture, but was pointing out some peculiar
characteristics of this disease as a biological curiosity on a wet Friday
afternoon. The prion disorders captured the imagination of a range of biologists
(including that teacher) well before the epidemic of bovine spongiform
encephalopathy (BSE) and the appearance of a new variant of the human prion
disease, Creutzfeldt Jakob disease (CJD), in the UK, because of their
extraordinary biology and the unique properties of the infectious agent. We
review the results of studies leading to a convergence of evidence that the
causative infectious agent, the 'prion', is devoid of nucleic acid and is
composed of an abnormal isoform of a host-encoded protein, the prion protein
(PrP).
PMID- 9657844
TI - Genetic dissection of testicular weight in the mouse with the BXD recombinant
inbred strains.
AB - Testicular weights were studied in the mouse BXD recombinant inbred (RI) strains.
These strains were derived from DBA/2J and C57BL/6J progenitors that differ
significantly in their testicular weights (0.224 g +/- 0.015 vs. 0.161 g +/-
0.03, P < 0.0001). The heritability of testicular weights was calculated to be
0.53, and the minimum number of responsible effective factors was estimated to be
5.7. The total genome scanning of the BXD RI strains with over 1000 markers
revealed a quantitative trait locus (QTL) on mouse Chromosome (Chr) 13 near the
D13Mit3 marker (LOD score 6.9). This QTL region was designated Twq1 and
associated with over 75% of genetic variability.
PMID- 9657845
TI - Genetics of obesity in KK mouse and effects of A(y) allele on quantitative
regulation.
AB - KK mouse is known as a polygenic model for noninsulin-dependent diabetes mellitus
with moderate obesity. To identify the quantitative trait loci (QTLs) responsible
for the body weight in KK, linkage analysis with 97 microsatellite markers was
carried out into 192 F2 progeny, comprising 93 mice with a/a genotype at agouti
locus and 99 mice with A(y)/a genotype, of a cross between C57BL/6J female and KK
A(y) (A(y) congenic) male, thereby the influence of A(y) allele on the
quantitative regulation of body weight was also examined. In F2 a/a mice, we
identified a QTL on Chromosome (Chr) 4, and two loci with suggestive linkage on
Chrs 15 and 18. In F2 A(y)/a mice, a QTL was identified on Chr 6, and two loci
with suggestive linkage were identified on Chrs 4 and 16. That the QTL on Chr 4
was held in common between F2 a/a and F2 A(y)/a progenies implies that this locus
may be a primary component regulating body weight in KK and KK-A(y). These
results suggest that the body weight in KK is controlled by multiple genes, and
the different combination of loci is involved in the presence of A(y) allele. The
QTL on Chr 6 seemed to determine the body weight by controlling fat deposition,
because the linkage was identified on body weight and adiposity, and is suggested
to be a component involved in the metabolic pathway in obesity caused by the A(y)
allele.
PMID- 9657846
TI - High-resolution mapping and recombination interval analysis of mouse chromosome
17.
AB - Analysis of homologous recombination in eukaryotes has shown that some meiotic
crossing-over occurs preferentially at specific genomic sites of limited physical
distance called recombinational hotspots. In the mouse, recombinational hotspots
have only been defined in the major histocompatibility complex (MHC) on
chromosome (Chr) 17. In an attempt to examine whether hotspots are unique to the
MHC or are present throughout the genome, high-resolution linkage maps of Chr 17
based on five backcrosses involving different inbred strains have been generated.
These maps separate many markers that were previously shown at the same map
position and allow a detailed analysis of recombination patterns across Chr 17.
Corresponding recombination intervals in these maps have been compared for the
identification of intervals with very little or no recombination in certain
genetic crosses and considerable recombination in other genetic crosses. This
approach has been termed Recombination Interval Analysis. Possible haplotype
dependent non-MHC hotspots, as well as previously identified MHC hotspots, have
been detected by interval analysis.
PMID- 9657848
TI - An integrated genetic linkage map of the laboratory rat.
AB - The laboratory rat, Rattus novegicus, is a major model system for physiological
and pathophysiological studies, and since 1966 more than 422,000 publications
describe biological studies on the rat (NCBI/Medline). The rat is becoming an
increasingly important genetic model for the study of specific diseases, as well
as retaining its role as a major preclinical model system for pharmaceutical
development. The initial genetic linkage map of the rat contained 432 genetic
markers (Jacob et al. 1995) out of 1171 developed due to the relatively low
polymorphism rate of the mapping cross used (SHR x BN) when compared to the
interspecific crosses in the mouse. While the rat genome project continues to
localize additional markers on the linkage map, and as of 11/97 more than 3,200
loci have been mapped. Current map construction is using two different crosses
(SHRSP x BN and FHH x ACI) rather than the initial mapping cross. Consequently
there is a need to provide integration among the different maps. We set out to
develop an integrated map, as well as increase the number of markers on the rat
genetic map. The crosses available for this analysis included the original
mapping cross SHR x BN reciprocal F2 intercross (448 markers), a GH x BN
intercross (205 markers), a SS/Mcw x BN intercross (235 markers), and a FHH/Eur x
ACI/Hsd intercross (276 markers), which is also one of the new mapping crosses.
Forty-six animals from each cross were genotyped with markers polymorphic for
that cross. The maps appear to cover the vast majority of the rat genome. The
availability of these additional markers should facilitate more complete whole
genome scans in a greater number of strains and provide additional markers in
specific genomic regions of interest.
PMID- 9657847
TI - An improved linkage map of rat chromosome 3 with three mapping panels.
AB - Our purposes were to develop an improved linkage map for rat Chromosome 3 and to
develop new markers polymorphic between Dahl salt-sensitive (S) and Dahl salt
resistant (R) rats. The linkage mapping panel consisted of three F2 populations
totaling 359 rats. Twenty-five new markers were developed and placed on the
linkage map. About half of these markers (13) were polymorphic between S and R
rats. The final map spans 124.7 centiMorgans (cM) and includes 64 markers. The
average distance between adjacent markers is 1.9 cM, and the largest separation
is 10.5 cM.
PMID- 9657849
TI - Construction of a rat genetic map by using randomly amplified microsatellite
polymorphism (RAMP) markers.
AB - Many rat strains have been employed in the genetic study of quantitative traits
such as blood pressure. In such genetic studies, it is essential to prepare rat
genetic maps fine enough to identify the genes regulating quantitative traits.
However, it is not an easy task to isolate a sufficient number of genetic markers
polymorphic between a particular pair of rat strains. In this study, we applied
the randomly amplified microsatellite polymorphism (RAMP) method, a simple method
to identify co-dominant markers (Wu et al. Nucleic Acids Res 22, 3257, 1994), to
isolate markers polymorphic between the stroke-prone spontaneously hypertensive
rat and the Wistar-Kyoto rat, a genetically hypertensive strain and its
normotensive control strain, which share a common genetic background. We
successfully identified 111 RAMP markers distributed throughout the rat genome
after screening 3046 sets of primers. We also showed that we could isolate
ordinary simple-sequence-length-polymorphism markers by cloning RAMP markers. The
RAMP method is a simple and efficient way to identify co-dominant genetic markers
on mammalian genomes.
PMID- 9657850
TI - Structural and functional analysis of the porcine secretory carrier membrane
protein 1 gene (SCAMP1).
AB - The secretory carrier membrane proteins (SCAMPs) are highly conserved integral
vesicle membrane components of the post-Golgi secretory and endocytic pathways.
We have isolated and characterized the porcine SCAMP1 cDNA and gene coding for a
variant of the SCAMP family. The SCAMP1 cDNA has a length of 3827 bp including a
133-bp 5' and 2701-bp 3' untranslated region. The mRNA has an open reading frame
of 1014 nt coding for a protein of 338 amino acids with a calculated molecular
mass of 37.9 kDa and a pI of 7.9. The porcine SCAMP1 is 97.04% identical with the
human and rat paralogs, respectively. The SCAMP1 gene consists of nine exons with
sizes ranging from 78 to 2842 bp and spans at least 70 kb of genomic DNA on
porcine Chromosome (Chr) 2q21-q22. The promoter of the SCAMP1 gene is TATA-box
less, and transcription starts at a G-nucleotide 133 nt upstream the start codon.
PMID- 9657851
TI - A QTL with major effect on milk yield and composition maps to bovine chromosome
14.
AB - A whole genome scan was undertaken in a granddaughter design comprising 1158
progeny-tested bulls in order to map QTL influencing milk yield and composition.
In this paper we report the identification of a locus on the centromeric end of
bovine Chromosome (Chr) 14, with major effect on fat and protein percentage as
well as milk yield. The genuine nature of this QTL was verified using the grand2
daughter design, that is, by tracing the segregating QTL alleles from
heterozygous grandsires to their maternal grandsons and confirming the predicted
QTL allele substitution effect.
PMID- 9657852
TI - Comparative analysis of 82 expressed sequence tags from a cattle ovary cDNA
library.
AB - In total, 82 ESTs were generated from 51 unique clones randomly selected from a
cattle ovary cDNA library. Among these clones, 22 (42.1%) had 5' and/or 3' ends
that matched with known human or other mammalian coding sequences, 18 (35.3%)
matched human or other ESTs, and 11 (21.6%) represented novel transcripts with no
significant match to any sequence in the databases. The relatively high frequency
of ESTs with no matches in GenBank or dbEST indicates that bovine ovary may be a
source of novel candidate genes for loci affecting cattle reproduction traits.
Primers were designed for 11 ESTs that had human orthologs in GenBank. These ESTs
were mapped to 10 bovine autosomes by PCR screening of a somatic cell hybrid
panel. Among these 11 ESTs, 4 corresponded to genes previously mapped in humans
and had chromosome assignments on the bovine map that were consistent with
available comparative mapping data. Although the human orthologs of the remaining
7 mapped bovine ESTs have not been mapped, the human map location could be
predicted on the basis of existing comparative mapping data. Because of the
general utility of our approach for comparative genome analysis, we have termed
it comparative mapping by annotation and sequence similarity (COMPASS). With the
cost of large-scale EST sequencing becoming more affordable, and the rapid
expansion of DNA databases, it is likely that COMPASS will be a preferred
strategy for high throughput comparative mapping.
PMID- 9657853
TI - A SINE species from hippopotamus and its distribution among animal species.
AB - Thirty sequences of a short interspersed repetitive element (SINE) were isolated
from genomic DNA of Hippopotamus amphibius (hippopotamus). RNA polymerase III
split promoter sequence was observed in all of the 30 sequences; and poly(A)-like
structure at 3'-end, as well as direct repeat flanking to the repetitive sequence
in many of the 30 sequences. A comparison of the consensus sequence of the 30
sequences with sequences in a DNA database (DDBJ/GENBANK/EMBL) revealed 93%
homology to the consensus sequence of a whale SINE, CHR-2, and 73% homology to
mouse glutamic acid tRNA. Phylogenetic analysis of tRNA-related regions of the
sequences with all of the mouse tRNAs revealed that glutamic acid tRNA was
genetically closest to the hippopotamus SINE. In addition, the tRNA-related
region of the consensus sequence was folded into a cloverleaf structure as with
mouse glutamic acid tRNA. These findings led us to conclude that the SINE of
hippopotamus was genetically related to a whale SINE, CHR-2 [the hippopotamus
SINE was named CHR-2(hippo)] and was a retroposon derived from glutamic acid
tRNA. Hipo53 and hipo95, which were the genetically most separated CHR-2(hippo)
sequences in the present study, were used as a probe for dot-blot hybridization
to examine the distribution of their homologous sequences among animal species.
Although the distribution spectra of hipo53 and hipo95 homologous sequences in
animal species differed to some extent, large amounts of both sequences were
found in Hippopotamus amphibius and Globicephala macrorhynchus (whale); and small
amounts in most of the animal species in Artiodactyla examined. These findings
indicated that the hippopotamus and whale had more recently branched off from the
clade that includes chevrotain and pecorans than the other animal species in the
clade. The 30 CHR-2(hippo) sequences were aligned, and the substitution rates
among the sequences were calculated with a different substitution rate model for
transition and for transversion. The calculation combined with the mutation rate
of the pseudogenes (r = 4.6 x 10(9)) indicated that CHR-2(hippo) sequences
diversified at least 132 million years ago (Myr).
PMID- 9657854
TI - Chromosomal localization and characterization of the stannin (Snn) gene.
AB - Stannin is a protein that has been localized to trimethyltin-sensitive cell
populations, and evidence suggests it plays a role in the toxic effects of
organotins. In this study, we have isolated a mouse stannin genomic clone and
have characterized the gene's intron-exon organization, promoter region, and
chromosomal location. We have also isolated a partial human stannin cDNA clone
and analyzed the open reading frame. The mouse genomic clone spans approximately
19 kb and consists of one intron and two exons. The splice site consensus
sequence was maintained at all intron-exon junctions. Promoter analysis suggests
that two putative promoter sites exist, each containing multiple regulatory
elements and transcription factor-binding sites. Fluorescence in situ
hybridization analysis localized stannin to mouse Chromosome (Chr) 16 at band A2.
This region is homologous to the proximal region of human Chr 16 (16p13) to which
stannin has been previously mapped. Sequence analysis revealed that the 264-bp
open reading frame was identical between rat and mouse. The human sequence was
98% identical, with two amino acid substitutions near the c-terminal end of the
peptide. These data suggest that stannin is highly conserved between species, and
its unusual pattern of cellular expression may, in part, be explained via cell
specific promoters.
PMID- 9657855
TI - Gene structure and map location of the murine homolog of the Huntington
associated protein, Hap1.
AB - Huntington's Disease (HD) is an inherited progressive neurodegenerative disorder
associated with a mutation in a gene expressed in both affected and non-affected
tissues. The selective neuropathology in HD is thought to be mediated in part
through interactions with other proteins including the Huntington Associated
Protein, HAP-1, which is predominantly expressed in the brain. We have mapped its
murine homolog, Hap1, to mouse Chr 11 (band D), which shares extensive synteny
with human Chr 17 including the region 17q21-q22, where the gene for
'frontotemporal dementia and parkinsonism linked to chromosome 17' has bee
mapped. In addition, we have sequenced a 21,984 base pair (bp) genomic clone
encompassing the entire Hap1 gene. It is organized as 11 exons and flanked by
exons from potentially one or more novel genes. At least three Hap1 transcripts
(Hap1-A; Hap1-B; Hap1-C) can be formed by alternative splicing at the 3' end of
the gene leading to protein isoforms with novel C-termini.
PMID- 9657856
TI - Genomic structure and chromosome location of the murine PDE1B phosphodiesterase
gene.
AB - Cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and
cGMP, thereby participating in regulation of the intracellular concentrations of
these second messengers. The PDE1 family is defined by regulation of activity by
calcium and calmodulin. We have cloned and characterized the mouse PDE1B gene,
which encodes the 63-kDa calcium/calmodulin-dependent PDE (CaM-PDE), an isozyme
that is expressed in the CNS in the olfactory tract, dentate gyrus, and striatum
and may participate in learning, memory, and regulation of phosphorylation of
DARPP-32 in dopaminergic neurons. We screened an I-129/SvJ mouse genomic library
and identified exons 2-13 of the PDE1B gene that span 8.4 kb of genomic DNA.
Exons range from 67 to 205 nucleotides and introns from 91 to 2250 nucleotides in
length. Exon 1 was not present in the 3 kb of genomic DNA 5' to exon 2 in our
clones. The mouse PDE1B gene shares many similar or identical exon boundaries as
well as considerable sequence identity with the rat PDE4B and PDE4D genes and the
Drosophila dunce cAMP-specific PDE gene dnc, suggesting that these genes all
arose from a common ancestor. Using fluorescence in situ hybridization, we
localized the PDE1B gene to the distal tip of mouse Chromosome (Chr) 15.
PMID- 9657857
TI - Traced orthologous amplified sequence tags (TOASTs) and mammalian comparative
maps.
AB - Progress on mammalian comparative maps could be significantly accelerated by
developing reagents defining orthologous landmarks in the genome of many
mammalian species. Using the large databases of gene sequences, we designed 225
orthologous gene-specific primer pairs corresponding to 146 functional genes. Of
these 225 primer pairs, 155 (68.9%), 182 (80.9%), 126 (56.0%), and 82 (36.4%)
produced a single PCR product when tested against human, pig, dog, and hamster
genomic DNA, respectively. In addition to the general rules of primer designing,
particular factors must be taken into consideration when choosing gene-specific
universal primers--for instance, preference for single-exon regions or highly
conserved segments among species, avoidance of GC-rich regions. Sequencing all
the canine PCR products traced by these primers demonstrated that of 123 traced
canine fragments with readable and reliable sequences, 121 (98.4%) were found to
match the GenBank orthologous sequences used for designing the primers, after a
BLAST search. Comparative characterization of PCR fragments among human, pig,
dog, and hamster revealed that the length of a single exon was much conserved
among species, with few exceptions. As the fragments were traced with
amplification by orthologous gene-specific primers, we suggest they be termed
Traced Orthologous Amplified Sequence Tags (TOASTs).
PMID- 9657858
TI - The dominant mouse mutations fused toes (Ft) and oligosyndactylism (Os) are not
allelic.
PMID- 9657859
TI - Male sex determination in the spiny rat Tokudaia osimensis (Rodentia: Muridae) is
not Sry dependent.
PMID- 9657860
TI - Localization of the genes encoding the type I diabetes autoantigens, protein
tyrosine phosphatases IA2 and IAR.
PMID- 9657861
TI - Characterization of murine BCAT genes: Bcat1, a c-Myc target, and its homolog,
Bcat2.
PMID- 9657862
TI - Genetic mapping of the Na(+)-taurocholate cotransporting polypeptide to mouse
chromosome 12.
PMID- 9657865
TI - Volume 247, Number 1 (1997), in Article No. AB972008, "High-Performance Liquid
Chromatographic Determination of Nitric Oxide Synthase-Related Arginine
Derivatives in Vitro and in Vivo," by Jens Meyer, Nadja Richter, and Markus
Hecker, pages 11-16:
AB - Copyright
PMID- 9657863
TI - Assignment of the growth hormone receptor gene to band q17 of the homeologous
sheep 16 and cattle 20 chromosomes.
PMID- 9657866
TI - Volume 255, Number 1 (1998), in Article No. AB972457, "Three-Minute G+A Specific
Reaction for DNA Sequencing," by Song-Tao Liu and Guo-Fan Hong, pages 158-159:
AB - Copyright
PMID- 9657867
TI - Characterization of proteins utilized in the desulfurization of petroleum
products by matrix-assisted laser desorption ionization time-of-flight mass
spectrometry.
AB - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
(MALDI/TOF/MS) with delayed extraction is utilized in linear, reflected-ion and
post-source decay (PSD) modes to directly characterize enzymes being developed
for use in a petroleum desulfurization process. The DNA sequence for the genes
isolated from Rhodococcus sp. strain IGTS8 that produce three of the four enzymes
under study had been previously reported with a discrepancy in residue
assignments for one of the enzymes, dsz-C. The use of proteolytic digests
followed by MALDI/TOF/MS with delayed extraction in the reflected-ion mode
provided sequence-specific information with mass accuracies exceeding 40 ppm over
a range of masses and signal-to-noise values. Peptide mapping of >80% of the
residues was accomplished for all four proteins. The use of PSD established the
true sequence for dsz-C, resolving the discrepancy in the literature. A
posttranslational loss of N-terminal methionine was observed for each of the four
proteins in linear MALDI/MS and was reconfirmed by peptide mapping for three of
the proteins.
PMID- 9657868
TI - A quantitative mannose 6-phosphate receptor-based in vitro assay for recombinant
human N-acetylgalactosamine-4-sulfatase.
AB - An assay was developed, using two similar formats, to simultaneously measure both
the lysosomal targeting receptor binding and enzyme activity of the recombinant
human enzyme N-acetylgalactosamine-4-sulfatase. This assay also has potential
application for all phosphorylated lysosomal enzymes that contain mannose-6
phosphate residues. The receptor was either purified from fetal bovine sera then
adsorbed, or produced in situ by growing and fixing diploid human fibroblast-like
cells, to a solid phase. The enzyme substrate was 4-methylumbelliferyl sulfate
which fluoresces after cleavage of the sulfate moiety. Both the precursor and
mature forms of the recombinant enzyme were used to demonstrate the specificity
and usefulness of the assay. The assay is rapid and sensitive and has a wide
dynamic range. Association between the receptor and the mannose-6-phosphate
residues was abrogated in the presence of a competitive inhibitor, mannose 6
phosphate. However, partial activity was still measured when the mature enzyme
was incubated in the presence of mannose 6-phosphate when using the fixed
fibroblast format. This would indicate that the recombinant enzymes contain at
least one terminal sugar moiety other than mannose 6-phosphate which can
recognize receptors on the surface of human fibroblast-like cells. Other possible
applications of this assay are also discussed.
PMID- 9657869
TI - Reconstituting ubiquitination reactions with affinity-purified components and 32P
ubiquitin.
AB - The discovery of protein ubiquitination in a broad range of organisms and
experimental settings has raised the need for a straightforward way to
characterize the mechanism of substrate targeting, using purified components. The
mechanism of ubiquitin conjugation to proteins has been extensively studied and
is mediated by a family of evolutionarily conserved proteins. We have used
previously described expression systems to purify the relevant targeting
components of the ubiquitin system. These methods yielded substantial amounts of
highly purified and catalytically active enzymes that permitted their use in
reconstituting protein ubiquitination. We monitored ubiquitination reactions with
32P-ubiquitin rather than 125I-ubiquitin. This advance makes the procedure
accessible to a broader range of experimentalists, since it eliminates the
additional concerns involved in handling 125I-isotope. Furthermore, the
strategies described here can be used to investigate the effects of specific
mutations introduced into ubiquitin or the targeting components (E1, Ubc/E2, and
E3) of this pathway.
PMID- 9657870
TI - Detection of the hereditary hemochromatosis gene mutation by real-time
fluorescence polymerase chain reaction and peptide nucleic acid clamping.
AB - Hereditary hemochromatosis (HH), an iron overload disease, is the most common
known inheritable disease. The most prevalent form of HH is believed to be the
result of a single base-pair mutation. We describe a rapid homogeneous mutation
analysis method that does not require post-polymerase chain reaction (PCR)
manipulations. This method is a marriage of three emerging technologies: rapid
cycling PCR thermal cyclers, peptide nucleic acid (PNA) probes, and a new double
stranded DNA-selective fluorescent dye, Sybr Green I. The LightCycler is a rapid
thermal cycler that fluorometrically monitors real-time formation of amplicon
with Sybr Green I. PNAs are DNA mimics that are more sensitive to mismatches than
DNA probes, and will not serve as primers for DNA polymerases. PNA probes were
designed to compete with PCR primers hybridizing to the HH mutation site. Fully
complemented PNA probes at an 18:1 ratio over DNA primers with a mismatch result
in suppression of amplicon formation. Conversely, PNA probes with a mismatch will
not impair the binding of a complementary primer, culminating in amplicon
formation. A LightCycler-based rapid genetic assay has been developed to
distinguish HH patients from HH carriers and normal individuals using PNA
clamping technology.
PMID- 9657871
TI - Adaptor ligation-based polymerase chain reaction-mediated walking.
AB - An improved method of adaptor ligation PCR was developed for isolation of unknown
sequences flanking a known DNA sequence. It was determined that the specificity
of the adaptor ligation-based walking technique could be significantly enhanced
by using uniquely blocked adaptors along with removal of unligated genomic DNA by
exonuclease III digestion. This technique was utilized to isolate three novel
promoter regions from three different Zea mays (maize) peroxidase genes.
Sequences encoding a putative maize 6-phosphogluconate dehydrogenase gene were
also isolated and confirmed by sequence analysis. The described improvements
could be applied to other existing adaptor ligation-based PCR walking techniques.
PMID- 9657873
TI - In vitro measurement of beta-lactamase-catalyzed ampicillin hydrolysis by
recombinant Escherichia coli extracts using quantitative high-performance liquid
chromatography.
AB - We report a rapid and simple protocol for measuring the beta-lactamase activity
from recombinant Escherichia coli cells transformed with any of the common
plasmid vectors that provide ampicillin resistance through constitutive
expression and periplasmic localization of the beta-lactamase TEM-1. The
hydrolytic enzyme was extracted from the E. coli periplasm and the beta-lactamase
activity determined by measuring conversion of ampicillin to aminobenzyl
penicilloic acid using quantitative high-performance liquid chromatography. Under
saturating conditions the in vitro assay was linear as a function of both
incubation time and enzyme concentration. Application of this assay to
investigate TEM-1 expression, from two different protein expression vector
systems, demonstrated the potential importance of this assay in studies of
recombinant protein expression and translocation.
PMID- 9657872
TI - High-performance capillary electrophoretic characterization of different types of
oligo- and polysialic acid chains.
AB - We have carried out comparative structural analysis of novel oligo- and
polysialic acid chains from diverse sources. Controlled acid hydrolysates of (a)
colominic acid, alpha2-->8-linked homopolymer of N-acetylneuraminic acid
(Neu5Ac), (b) alpha2-->8-linked oligo/polyNeu5Gc chains present in rainbow trout
egg polysialoglycoprotein, and (c) alpha2-->8-linked oligomers of
deaminoneuraminic acid (KDN) residues of KDN-rich glycoprotein derived from
rainbow trout vitelline envelope were analyzed by high-performance capillary
electrophoresis (HPCE). The results showed that three different types of alpha2-
>8-linked oligosialic acids having same degree of polymerization can be separated
by HPCE. A partial hydrolysate of colominic acid with mild acid was shown by CE
to form intramolecular esters during the controlled hydrolysis and the subsequent
workup procedure. In contrast, lactonization of (-->5-Oglycolyl-Neu5Gcalpha2-
>)n, alpha2-->5-Oglycolyl-linked homopolymer of N-glycolylneuraminic acid
(Neu5Gc) present in the egg jelly coat of sea urchin, did not take place as
readily as in (-->8Neu5Acalpha2-->)n.
PMID- 9657874
TI - Single-molecule analysis of restriction DNA fragments using fluorescence
correlation spectroscopy.
AB - The cleavage of fluorescence-labeled M13DNA (7250 bp) using HaeIII, HgaI, BsmAI,
and BspMI was analyzed by fluorescence correlation spectroscopy (FCS) in a small
volume (1.5 x 10(-15) liters). The digestion process can be monitored by the
decrease in amplitude of the fluorescence correlation function while the original
DNA molecule is divided into several fragments by the enzymes. To analyze this
reaction by FCS, we derived a practical equation for estimating the number of
molecules in the FCS measurements. Under standard enzymatic conditions, HaeIII
and BsmAI digested fluorescence-labeled DNA to completion in the range of 8 h,
whereas HgaI and BspMI digested the DNA after 40 h. The comparison of recognition
sequences suggested that some tagged nucleotides could be inserted between the
recognition site and the cleavage site of the slow enzyme group. The decrease in
amplitude in the fluorescence correlation function quantitatively monitors the
hydrolysis of DNA during the digestion process.
PMID- 9657875
TI - Enzyme-complemented activatorsorbent assay (ECASA): genetic engineering for
enzyme-linked immunosorbent assay-type mercuric ion detection.
AB - The sensor component of bacterial mercury resistance systems is the
metalloregulatory protein MerR, which has nanomolar sensitivity and high
selectivity for Hg(II). A fusion protein of MerR and the alpha-peptide part of
beta-galactosidase (LacZalpha) was constructed by fusing the relevant genes. The
protein exhibited both MerR functions and alpha-complementing activity to the
inactive LacZDeltaM15 (M15) protein. The bifunctional character of the
appropriate MerR-LacZalpha-complemented M15 protein (MerR-LacZalpha:M15 protein
complex) was used to develop a Hg(II)-specific enzyme-complemented
activatorsorbent assay. Hg(II) was immobilized and presented on a matrix taking
advantage of the high affinity of Hg(II) to SH residues. The immobilized Hg(II)
could be specifically detected down to the parts-per-billion level by quantifying
the beta-galactosidase activity of the bound fusion protein complex.
PMID- 9657876
TI - High-yield deblocking of amino termini of recombinant immunoglobulins with
pyroglutamate aminopeptidase.
AB - For larger proteins, efficient deblocking prior to Edman sequencing is especially
important to obtain quality, extended sequencing data which is limited by the
stepwise accumulation of background from the random acid hydrolysis of the
protein. Therefore, any portion that remains blocked contributes to the
undesirable background. We report an optimized procedure for the removal of
pyroglutamate (pGlu) by pyroglutamate aminopeptidase (PGAP) and demonstrate its
use for the quantitative deblocking of several humanized recombinant antibodies
(rIgGs). The rIgGs with blocked heavy chain provided an advantageous system in
which removal of pGlu from the heavy chain was determined as a ratio of the
deblocked heavy chain to the light chain in the first cycle of sequencing; i.e.,
the light chain was used as an internal standard. The reaction temperature,
reaction time, enzyme-to-substrate ratio, denaturation, and
reduction/carboxymethylation prior to digestion, and different commercial enzymes
were evaluated. The optimized procedure involves reduction/carboxymethylation in
guanidine buffer, buffer exchange by gel-permeation chromatography, and overnight
PGAP digestion at 37 degrees C. Five different rIgGs, including one with blocked
heavy and light chains, were deblocked in nearly quantitative yields using this
procedure.
PMID- 9657877
TI - Nonradioactive phosphopeptide assay by matrix-assisted laser desorption
ionization time-of-flight mass spectrometry: application to calcium/calmodulin
dependent protein kinase II.
AB - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
(MALDI-TOF) was used to quantify the phosphopeptide produced by
calcium/calmodulin-dependent protein kinase II (CaMK II). MALDI-TOF measurements
were performed in a linear and positive ion mode with delayed extraction excited
at various laser powers and at different sampling positions, i.e., different loci
of laser illumination. We find that the ratio of the peak area of the substrate
(S) to that of its monophosphorylated form (SP) for a given mixture is constant,
independent of the laser powers and/or of the sample loci illuminated by the
laser. We also find that the fraction of phosphorylation determined by MALDI-TOF,
or fMALDI-TOF, is proportionally smaller than that determined by HPLC, or fHPLC;
the ratio fMALDI-TOF/fHPLC was 0.797 +/- 0.0229 (99% confidence limit, n = 7) for
a 30-mer peptide substrate used in this study. A low mass gate, which turns off
the detector temporarily, improved the ratio fMALDI-TOF/fHPLC to 0.917 +/- 0.0184
(99% confidence limit, n = 7). Our interpretation of this result is that the
reduction of the phosphopeptide peak in the MALDI-TOF measurement is likely to be
caused by a temporal loss of detector function rather than by a lower efficiency
of ionization for the phosphopeptide compared with its parent species. In these
measurements the experimental errors, up to the 50% phosphorylation state, were
less than 5%. After an adjustment made based on the fMALDI-TOF/fHPLC ratio of
0.917, MALDI-TOF gave an accurate measurement for the kinetics of the CaMK II
phosphorylation reaction. Since only a small volume of the reaction mixture,
typically containing 3 to 50 pmol of substrate, is required for the MALDI-TOF
measurement, this method can be adapted to a nonradioactive microscale assay for
CaMK II and also for other protein kinases.
PMID- 9657878
TI - Ethanol biosensors and electrochemical oxidation of NADH.
AB - Comparative studies of the electrochemical oxidation of reduced nicotinamide
coenzyme (NADH) at the surfaces of chemically modified graphite paste electrodes
(CMEs) are reported. Three different electroactive materials,
tetracyanoquinodimethane (TCNQ), tetrathiafulvalene (TTF), and dimethyl ferrocene
(dmFc), were used to construct three different chemically modified paste
electrodes. The oxidation of NADH was examined on the basis of cyclic
voltammetric measurements. The results show that all three mediators (TCNQ, TTF,
and dmFc) behave as efficient mediators of the oxidation of NADH. The typical
response curves of NADH at the CMEs surfaces are reported. Incorporating alcohol
dehydrogenase and electroactive materials (TCNQ, TTF, and dmFc) within the
graphite paste electrodes has led to the development of ethanol biosensors.
Typical response curves for the ethanol analysis are reported. Comparative
studies on the mediated electrochemical responses of the biosensors to ethanol
are discussed.
PMID- 9657879
TI - Distinguishing small molecular mass differences of proteins by mass spectrometry.
AB - Electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR)
mass spectrometry allows for high-resolution, accurate mass analysis of multiply
charged ions of proteins. In the work described here, the ability of ESI-FTICR to
distinguish small differences in molecular mass is evaluated. Ubiquitin was used
as an internal mass calibration standard to measure the molecular mass of
cytochrome c, myoglobin, and several carbonic anhydrase isoforms. Mass
calibration was based on the tallest isotopic peak of each ubiquitin charge
state. Ubiquitin performed well as an internal standard because its charge states
covered the appropriate mass range, interference was minimal, and the tallest
peak was easily identified. The peak masses of cytochrome c (12.5 kDa) and
myoglobin (17 kDa) were measured to an accuracy of about 0.02 Da (<2ppm).
However, errors of 1.0 Da were observed for some individual determinations
because of the difficulty in identifying the tallest peak. When the technique was
applied to bovine carbonic anhydrase II, even combining data from several charge
states did not yield an unequivocal assignment of the tallest peak, resulting in
a mass assignment of 29,023.7 or 29,024.7. Similarly, measurements of two
isoforms with a mass difference of 1 Da, human carbonic anhydrase I, pI 6.0 and
6.6, yielded overlapping values for the mass of the tallest peak. However, these
two isoforms were clearly distinguished by (a) identification of the tallest peak
using a measurement of average mass as a guide and (b) comparison of the isotopic
peak intensity patterns.
PMID- 9657880
TI - A binding shift assay for the zinc-bound and zinc-free HIV-1 nucleocapsid protein
by capillary electrophoresis.
AB - Affinity capillary electrophoresis was used to detect a shift in mobility when a
zinc ion binds to the highly basic nucleocapsid protein (NCp7) of HIV-1. NCp7
contains two Cys-X2- Cys-X4-His-X4-Cys zinc fingers. With constant concentrations
of NCp7 as a receptor and various concentrations of zinc as a ligand in the
sample buffer and the electrophoresis buffer, we observed changes in
electrophoretic mobilities of NCp7 protein when complexes were formed with zinc.
Scatchard analysis of the mobility indicates the presence of at least two types
of binding sites for zinc. At pH 6.0, one site is shown to bind zinc strongly
with a binding constant Kb = 3.25 x 10(5) M-1 and the second site has a Kb = 1.8
x 10(5) M-1. The binding of zinc to the first zinc finger decreased the affinity
of zinc for the second zinc finger approximately twofold. The Hill coefficient
for this negative cooperativity is 0.9. A series of NCp7 mutants were also
examined in the assay to determine their ability to bind zinc. This assay affords
a quick method to observe a zinc ion binding to NCp7 and to calculate binding
constants.
PMID- 9657881
TI - Methodological aspects of measuring human skeletal muscle electrolyte content and
ouabain binding capacity.
AB - The aim of the study was to evaluate the use of freeze-dried and dissected small
muscle biopsy specimens ("dry") for the determination of human muscle electrolyte
content and ouabain binding capacity, compared with an easier method, without
this freeze-drying step ("wet"). Freeze-drying and dissection of muscle biopsy
specimens reduced the variation in the determination of muscle potassium and
magnesium content. The total coefficient of variation was 8.6% in the dry
determination of muscle potassium content and 13.5% in the wet determination (P <
0.05). In the determination of muscle magnesium content, the total coefficient of
variation was 7.4% in the dry determination and 13.7% when determined wet (P <
0.005). Muscle sodium content had a very large coefficient of variation,
independent of the method used. The content of dry solids was too high in
biopsies which were incubated in Tris-vanadate buffer (31.9%), compared to
biopsies which were not incubated in Tris-vanadate buffer (24.9%, P < 0.001).
Hereby, the measured ouabain binding capacity became too high when measured wet.
In conclusion, muscle electrolyte content and ouabain binding capacity should be
determined after drying and microdissection of the biopsies, because this method
confers the least variation and the highest accuracy.
PMID- 9657882
TI - Spontaneous hydrolysis and dehydration of dehydroascorbic acid in aqueous
solution.
AB - The interaction of water with dehydroascorbic acid was examined by incubating
dehydroascorbic acid and ascorbic acid in 18O-labeled water for various amounts
of time and then oxidizing the products with hydrogen peroxide or reducing the
products with mercaptoethanol, with analysis by gas chromatography mass
spectrometry. Based on mass changes, dehydroascorbic acid readily exchanged three
oxygen atoms with H218O. When mercaptoethanol was used to reduce dehydroascorbic
acid (which had been incubated in H218O) to ascorbic acid, the newly formed
ascorbic acid also contained three labeled oxygen atoms. However, ascorbic acid
incubated in H218O for the same amount of time under identical conditions
exchanged only two labeled oxygen atoms. Electron impact mass spectrometry of
derivatized ascorbic acid created a decarboxylation product which had only two
labeled oxygen atoms, regardless if 3-oxygen-labeled or 2-oxygen-labeled ascorbic
acid was the parent compound, isolating the extra oxygen addition to carbon 1.
These data suggest that dehydroascorbic acid spontaneously hydrolyzes and
dehydrates in aqueous solution and that the hydrolytic-hydroxyl oxygen is
accepted by carbon 1. Ascorbic acid, on the other hand, does not show this same
tendency to hydrolyze.
PMID- 9657883
TI - Inactivation of alpha1-proteinase inhibitor as a broad screen for detecting
proteolytic activities in unknown samples.
AB - The need for a quick, simple screening method for the detection of general
proteolytic activity prompted us to determine whether cleavage within the
reactive site loop region (RSL) of alpha1-proteinase inhibitor (alpha1-PI), a
well-characterized member of the serpin family known to be susceptible to
proteolytic inactivation, can be utilized for this purpose. Inactivation of
alpha1-PI in the RSL region can be measured by loss of residual inhibitory
capacity of alpha1-PI against its target proteinase. While we originally utilized
this assay to detect a new proteinase from culture supernatants of Porphyromonas
gingivalis, the feasibility of extending this assay to scan for proteolytic
activity from other systems was also assessed. As an example, we found that the
serine proteinase from Staphylococcus aureus (SSP) had virtually the same
catalytic efficiency in inactivating alpha1-PI in our assay as it did in the
hydrolysis of the synthetic substrate Z-Phe-Leu-Glu-pNA (kcat/Km value of 2 x
10(4) M-1 s-1 vs 2.6 x 10(4) M-1 s-1, respectively). Additionally, in both assays
activity could be readily detected in less than a 1 h incubation at SSP
concentrations in the picomolar range. This assay is unique in that proteinases
which hydrolyze peptide bonds within the RSL of alpha1-PI can readily be detected
as measured by loss of alpha1-PI inhibitory activity.
PMID- 9657884
TI - Quantitation and characterization of cytochrome c oxidase in complex systems.
AB - Quantitation of cytochrome c oxidase in complex systems such as tissue
homogenates is often hampered by the presence of other hemoproteins. Cyanide can
bind to reduced cytochrome c oxidase from diverse sources with a dissociation
constant in the range of 0.1-0.5 mM and induces a characteristic optical change.
This contrasts with the very weak binding of cyanide to reduced forms of many
other hemoproteins, including hemoglobin and myoglobin. Hence, difference spectra
of cyanide binding to reduced samples can provide an improved method to resolve
and quantitate cytochrome c oxidase. In addition, the cyanide compound of
cytochrome c oxidase is photolabile. This property can be exploited to further
enhance the sensitivity of detection and analysis of cytochrome c oxidase.
PMID- 9657885
TI - Measurements of serotonin and related indoles using capillary electrophoresis
with multiphoton-induced hyperluminescence.
AB - We report the use of multiphoton-excited photochemistry to generate highly
fluorescent products from hydroxyindoles fractionated in submicron capillary
electrophoresis channels. In this approach, the near-infrared (750 nm) output
from a modelocked titanium:sapphire laser is focused at the outlet of a 0.6
micron i.d. capillary, producing pulse intensities of approximately 10(12) W cm-2
within a femtoliter focal volume. Hydroxyindole molecules migrating through the
outlet aperture of the capillary intersect the beam focus, where absorption of
three to four photons (approximately 1.65 eV photon-1) initiates a photobleaching
reaction. The resultant hydroxyindole photoproducts produce broadband visible
emission (lambdamax approximately 500 nm) when excited with two additional near
IR photons and appear substantially more resistant to photobleaching than the
parent hydroxyindoles. This multiphoton-induced conversion of analytes to
hyperluminescent derivatives thus offers a more sensitive approach than UV
fluorescence for detecting extremely small quantities of material. Mixtures of
the hydroxyindoles serotonin (5-hydroxytryptamine), 5-hydroxytryptophan, and 5
hydroxyindole acetic acid are reliably characterized (relative error
approximately 10%) in 100 s, with detection limits as low as approximately 70
zmol (approximately 42,000 molecules). The sensitivity of this measurement
strategy improves on the best previously reported results for capillary
separations of indoles by more than one order of magnitude.
PMID- 9657886
TI - Manually operated freeze-clamping press.
PMID- 9657887
TI - A simple latex agglutination format for DNA probe-based tests.
PMID- 9657888
TI - Colorimetric determination of chitosan.
PMID- 9657890
TI - Call for papers: adolescents and risk-taking
AB - Copyright 1998 The Association for Professionals in Services for Adolescents.
PMID- 9657889
TI - Two fluorometric approaches to the measurement of dextranase activity.
PMID- 9657891
TI - Childhood stress, behavioural symptoms and mother-daughter pubertal development.
AB - Belsky, Steinberg and Draper (Child Development 1991, 62, 647-670) predicted that
early childhood stress or conflict in the family environment would be associated
with childhood behavioural symptoms, early puberty and early, less discriminate
sexual behaviour. Their theory was tested in a retrospective self-report survey
in 28 daughters (aged 12 to 15) and 21 mothers. In daughters, earlier menarche
correlated with more family stress in a late childhood (age 7 to 11); more
conflict with mother in early childhood (birth to age 6); more rejection from and
less closeness to mother throughout childhood (birth to age 11); more anxiousness
and internalizing symptoms (anxiousness/depression) in late childhood (age 7 to
11); earlier age at dating boys; and more boyfriends. An alternative
interpretation is considered based on genetic transmission of maternal
characteristics.
PMID- 9657892
TI - Familial backgrounds and risk behaviors of youth with thrownaway experiences.
AB - Many homeless youth may also be considered "thrownaway" in that they have
specifically been told to leave home. In this study, thrownaway experiences among
homeless youth are examined in two national samples: (a) a nationally
representative sample of youth residing in youth shelters, and (b) a purposive
sample of street youth in 10 cities. Prevalence of thrownaway experiences for the
total samples and for demographic subgroups is provided, along with comparisons
of the familial backgrounds and high-risk behaviors of youth with and without
such experiences. In both samples, youth with thrownaway experiences (who
constituted nearly half of each sample) were more likely than youth without such
experiences to report (a) that they had attempted suicide, used marijuana and
other drugs (excluding cocaine), and had been involved in the drug trade and
carried hidden weapons; (b) that other family members had used illicit drugs
during the 30 days before the youth left home; and (c) that they had spent at
least 1 night away from home due to physical and/or emotional abuse or neglect,
familial conflict, and familial substance use. Thrownaway youth constitute a
particularly vulnerable subpopulation of homeless youth. A greater recognition
and understanding of such youth will facilitate design of services that better
address their needs.
PMID- 9657893
TI - The effects of work and relational mental incongruity on identity formation and
well-being.
AB - By combining concepts of Tazelaar's mental incongruity theory (1983) and Marcia's
identity model (1993) we tried to uncover some theoretical mechanisms that may
underlie progressive developmental trends in identity status. Mental incongruity
is what people experience when there is a discrepancy between how they think a
situation should be (the standard) and how they experience the actual situation
or their own behaviour (the cognition). In both the work and relational domain,
the influence of adolescents' standards and mental incongruity on the development
of their identity was studied. By means of structural equation modelling, we
tested hypotheses on a representative sample of Dutch working adolescents, aged
16 to 24 (n=706). As expected, a higher standard in the relational or work domain
was related to more exploration and commitment in that domain - and thus to a
more developed identity. Work and relational identity were positively related to
well-being. Furthermore, positive relations were found between a standard and the
mental incongruity in a domain. Finally, mental incongruities were negatively
related to identity and only relational incongruity was negatively related to
well-being.
PMID- 9657894
TI - The acquisition, development and maintenance of lottery and scratchcard gambling
in adolescence.
AB - The U.K. National Lottery and instant scratchcards are now well established yet
there is still little empirical research on the players. This study was an
exploratory investigation of the psychosocial effects of these forms of gambling
among adolescents (n=1195; aged 11- to 15-years-old). Using a questionnaire, it
was shown that large numbers of adolescents were taking part in these activities.
There was a significant link between parental and child gambling with most
lottery tickets and scratchcards being bought for the adolescents by their
parents. Results showed that many adolescents thought they would win lots of
money on these activities and that these activities were in general not perceived
to be forms of gambling. Six per cent of adolescents fulfiled the DSM-IV-J
criteria for pathological gambling, the majority of which were males.
PMID- 9657895
TI - Adolescents' and children's knowledge about rights: some evidence for how young
people view rights in their own lives.
AB - The present study examined the development of knowledge about rights from
childhood to adolescence. One hundred and sixty-nine 8-16-year-olds participated
in individual semi-structured interviews assessing knowledge and importance of
rights both generally and in children's and adolescents' lives. Detailed content
analyses indicated that a global stage account may not capture key features of
the development of young people's knowledge about rights. Even the oldest
adolescents consistently "defined" rights in concrete rather than abstract terms.
In contrast, by 10 years of age the majority of subjects were aware of the
universal nature of rights. These results suggest that what adolescents and
children think about rights appears to be influenced by how they view rights in
their own lives. The findings are discussed in terms of developmental theory and
in relation to practical implications for children's rights.
PMID- 9657896
TI - The relationship between early maltreatment and teenage parenthood.
AB - In a longitudinal study of the effects of early childhood maltreatment, 92
adolescents who had become parents while under 20 years of age were compared to
297 adolescents who had not become parents during their teenage years. Preschool
and school-age physical abuse alone and in combination with neglect were found to
have significant relationships with teenage parenthood. Low self-esteem, as
evaluated by elementary school teachers, was related to both early maltreatment
and teenage parenthood. Sexual abuse, based on retrospective reports of the
adolescents, had a significant but weaker relationship to teenage parenthood. The
implications of these findings and the findings that high school dropout,
assaultive behavior, and drug use are also related to teenage parenthood are
discussed.
PMID- 9657897
TI - Adolescents' perceptions of communication with parents relative to specific
aspects of relationships with parents and personal development.
AB - Adolescents' views of communication with their parents are examined in relation
to measures of family satisfaction, adolescent decision-making and disagreement
with parents (Study I), and to measures of self-esteem, well-being and coping
(Study II). The results provide some support for the psychometric qualities of
the Parent-Adolescent Communication Scale (PACS) and suggest that good family
communication is associated with satisfaction with the family and with lack of
disagreement between adolescents and parents. They also indicate a positive
association between family communication and adolescent self-esteem, certain
aspects of adolescent well-being and type of coping strategy employed.
PMID- 9657898
TI - Identity status and empathic response patterns: a multidimensional investigation.
AB - This study examined the multidimensional empathic response patterns of late
adolescent undergraduate students according to their identity status. Subjects
were 153 undergraduates at seven New York City area colleges. Subjects completed
self-report measures of empathic response style and identity development.
Empathic concern showed a statistically significant positive linear relationship
with the identity status hierarchy. Cognitive empathy had a statistically
significant positive relationship, and empathic distress had a statistically
significant negative relationship with identity exploration. Findings are
discussed in the context of developmental and social-cognitive models of identity
status.
PMID- 9657900
TI - Reviewers
AB - Copyright 1998 The Association for Professionals in Services for Adolescents.
PMID- 9657899
TI - Brief report: the temperamental characteristics of the Chinese adolescents in
Taiwan.
AB - A Chinese Adolescent Temperament Self rating questionnaire was completed by 1165
Chinese adolescents from high schools in or near Taipei City, Taiwan. Statistical
analysis revealed the following results: (a) boys tended to show higher activity
level, higher task orientation, higher intensity of reaction, higher tactile
threshold and lower adaptability than girls; (b) junior graders tended to have
lower rhythmicity, less initial approaching reaction toward new stimuli and lower
adaptability than senior graders; (c) the eldest child tended to have higher
adaptability, higher task orientation and higher rhythmicity than younger
siblings in the family; and (d) those with a better educated father tended to
have more positive mood, higher task orientation, higher adaptability, higher
rhythmicity and more initial approaching reaction.
PMID- 9657901
TI - The effect of ascorbic acid and ferric ammonium citrate on iron uptake and
storage in lens epithelial cells.
AB - Ferritin is the major intracellular iron storage protein which has been shown to
protect cells against oxidative damage. Recent reports that an inherited
abnormality in human ferritin synthesis is associated with early bilateral
cataracts underscore the importance of understanding ferritin synthesis and iron
storage in lens epithelial cells. We previously demonstrated that ascorbic acid
greatly increases de novo synthesis of ferritin in lens epithelial cells. The
objectives of the present study were to determine: (1) the effects of ascorbic
acid and ferric ammonium citrate on iron uptake by canine lens epithelial cells
from iron bound to transferrin and from ferric chloride and (2) the incorporation
of this element into ferritin. Iron uptake by lens epithelial cells from 59ferric
chloride was 20 times higher than from 59iron-transferrin and iron deposition
into ferritin was 8-fold higher when 59ferric chloride was the source. Ascorbic
acid had a stimulatory effect on iron uptake from transferrin and on
incorporation of this element into ferritin. The ascorbic acid-induced increase
of iron uptake required de novo protein synthesis but not specifically de novo
ferritin biosynthesis. Although ferritin is not directly involved in iron uptake,
the level of ferritin protein could control the pool of intracellular iron. The
present results indicate that iron homeostasis in lens epithelial cells is
affected mainly by changes in apoferritin synthesis, which is greatly stimulated
by ascorbic acid, rather than by altering the rate of protein degradation, which
is very slow in these cells under all circumstances. Ferric ammonium citrate
activates iron uptake from transferrin in a wide range of cell lines by
generation of free radicals. Ferric ammonium citrate also increased iron uptake
from Tf in lens epithelial cells. Ferric ammonium citrate treated cells
incorporated 5 times more iron and deposited 2 times more iron into ferritin than
control cells. Increased incorporation of iron into ferritin was due to ferric
ammonium citrate-induced stimulation of de novo ferritin synthesis rather than an
increased rate of iron deposition into pre-existing ferritin. Ferric ammonium
citrate had a different effect on iron uptake from ferric chloride; total iron
uptake was not significantly increased while deposition into ferritin was
significantly decreased. These results demonstrate that iron homeostasis in lens
epithelial cells is regulated by ascorbic acid and by changes in the rate of de
novo ferritin synthesis. In addition, the differences in iron uptake from
transferrin and ferric chloride and its subsequent incorporation into ferritin
suggests that the mechanisms by which iron is incorporated into ferritin are
source dependent.
PMID- 9657902
TI - ETA receptor mediated inhibition of intracellular pH regulation in cultured
bovine corneal epithelial cells.
AB - The contributions were determined in primary cultures of bovine corneal
epithelial cells (BCEC) of Na:H exchange (NHE) and vacuolar H+-ATPase (i.e. V
type) activity to the regulation of intracellular pH (pHi). Furthermore, we
characterized the effects on pHi regulation of exposure to 1 microM ET-1 under
control and acid loaded conditions. With the pH sensitive dye, 2',7' Bis
(carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM), the control
pHi was 7.1 in NaCl (nominally HCO3-free) Ringers. Inhibition of NHE with 100
microM dimethylamiloride (DMA) rapidly decreased pHi by 0.37 units. Similarly,
selective inhibition of V-type H+-ATPase with 10 microM bafilomycin A1 decreased
pHi by 0.22 units. Following acid loading in NaCl Ringers with a 20 mm NH4Cl
prepulse, pHi recovery was partially inhibited by exposure to either Na-free
(NMGCl) Ringers, 100 microM DMA or 20 microM bafilomycin A1. Based on decreases
in H+ efflux resulting from selective inhibition of NHE and V-type H+ pump
activity, NHE activity accounts for 76% of the pHi recovery following acid
loading. Under control conditions, ET-1 (1 microM) had no effect on pHi whereas
ET-1 completely suppressed pHi recovery following acid loading in NaCl or NMGCl
Ringers. This inhibitory effect was largely due to stimulation of ETA because in
the presence of BQ-123 (10 microM), a selective ETA receptor antagonist, pHi
recovery was completely restored. Suppression of pHi recovery also occurred
following stimulation of protein kinase C (PKC) with 10(-7) m phorbol myristate
(PMA) whereas 10(-7) m 4 alpha phorbol 12,13 didecanoate (PDD) had no effect. ET
1 failed to suppress pHi recovery after inhibition of PKC with 0.5 microM
calphostin C suggesting that the inhibition of pHi recovery by ET-1 is a
consequence of PKC stimulation. Similarly, inhibition of Ca2+-dependent
calmodulin stimulated CaM II kinase with KN-62 (10 microM) reversed the
suppression of pHi recovery by ET-1. Preinhibition of either protein phosphatase
(PP), PP-1, PP-2A or PP-2B activity with 1 microM phenylarsine oxide, 10 nm
okadaic acid, 10 microM cyclosporin A1 or 20 microM BAPTA, also obviated the
suppression of pHi recovery by ET-1. Therefore ETA receptor mediated inhibition
of pHi regulation following acid loading could be a consequence of either PKC or
CaMII kinase stimulation. Each one of these kinases may in turn phosphorylate and
thereby stimulate the activities of PP-1, PP-2A or PP-2B. An increase in the
activity of any one of these protein phosphatases could lead to dephosphorylation
of the NHE and V-type H+ pump. This alteration may prevent them from becoming
adequately stimulated to elicit pHi recovery in response to acid loading.
PMID- 9657903
TI - Hyalocyte-like cells are more numerous in the posterior chamber than they are in
the vitreous of the rabbit eye.
AB - The distribution and concentration of free cells inside the eye chambers of
rabbits were investigated using semi-quantitative analysis of histological
paraffin sections. Studies using light (methacrylate sections) as well as
transmission and scanning electron microscopy were undertaken for the
morphological characterization of the free cells. Immunocytochemistry and
autoradiography were employed in an attempt to find out their nature and their
origin, respectively. It was observed that cells morphologically similar to the
vitreous hyalocytes were more numerous inside the posterior chamber than were the
hyalocytes in the cortical vitreous. Neither the hyalocytes nor the posterior
chamber cells reacted with an antibody to rabbit macrophages. The finding of
labeled free cells after an intravitreal injection of 3H-thymidine indicates that
these cells can renew themselves and that their number does not depend
exclusively on monocytes migrating from the blood stream to the eye chambers, as
is believed to occur. In conclusion, hyalocytes or hyalocyte-like cells are more
concentrated in the posterior chamber than they are in the vitreous. Both the
hyalocytes and the posterior-chamber cells could not be characterized as fully
developed macrophages.
PMID- 9657904
TI - Changes in the pupillary light reflex of pigmented royal college of surgeons rats
with Age.
AB - We studied the latency and amplitude of the pupillary light reflex response of
the Royal College of Surgeons rat from 10 to 52 weeks of age. The responses of
these dystrophic rats were diminished compared to those of normal, non-dystrophic
rats at all ages examined. This was most marked at the dimmest light intensity
studied here and for the latency of dystrophic animals' responses. The latency
deteriorated over the course of 52 weeks, although there was some evidence of
improvement beyond 36 weeks of age. The amplitude of the dystrophic animals'
responses also suggested some deterioration occurring up to 36 weeks of age, but
with a substantial improvement beyond this time. In addition to these parameters,
we also observed a break in the constriction phase of the pupillary light reflex
that was unique to the dystrophic animals' responses. The frequency with which
the anomaly occurred decreased in a light-dependent manner with age. The
improvement of the pupillary light reflex at older ages, even when very few
photoreceptors remain, may reflect compensatory events occurring in the inner
retinal layers and/or in the central connections of the pupillary light reflex
pathway. We suggest that the break in the constriction phase is a reflection of
dual inputs driving the response, one of which is affected more by the
degenerative events. This study provides baseline data on the effect of
degeneration on function over time which can be used to evaluate the efficacy of
repair strategies such as transplantation.
PMID- 9657905
TI - The effect of dexamethasone on integrin and laminin expression in cultured human
trabecular meshwork cells.
AB - Glucocorticoid treatment in vivo can produce a glaucoma similar in many ways to
POAG. Treatment of trabecular meshwork cells in culture with dexamethasone allows
the study of biochemical aspects of this disease process. The effects of
dexamethasone on the expression of integrins and laminin in both normal and
glaucomatous cultured human trabecular meshwork cells were evaluated. Human
trabecular meshwork cell lines were cultured for 18 days in the presence or
absence of 10(-7) m dexamethasone. Radioimmunoprecipitation was used to determine
the relative expression of five alphaintegrin subunits. Laminin expression was
evaluated with Western blots. Laminin was increased in all cell lines following
dexamethasone treatment. alpha2, alpha5 and alphaV integrin chains showed
consistent dexamethasone-induced changes in expression, while alpha3 and alpha4
subunits did not. There were no differences in the expression patterns for any of
these integrin subunits between normal and glaucomatous cell lines. Increased
laminin deposition as seen in this study with dexamethasone treatment may be
partially responsible for the decreased outflow facility seen in both steroid
induced glaucoma and in POAG.
PMID- 9657906
TI - Transforming growth factor-beta induced protein, betaIG-H3, is present in
degraded form and altered localization in lattice corneal dystrophy type I.
AB - Lattice corneal dystrophy type I (LCDI) is an inherited autosomal dominant local
amyloidosis, restricted to the corneal stroma. Comparison of electrophoretic
profiles of normal and dystrophic corneas revealed a 42 kD protein, which was
present only in dystrophic corneas. The N-terminal sequence of this protein
showed identity to transforming growth factor-beta induced gene product (betaIG
H3). A polyclonal antiserum was raised in chicken against a synthetic peptide
identical to the N-terminal portion of betaIG-H3. On immunoblots, the antiserum
stained the 42 kD band, and also a 68 kD band corresponding to the reported
molecular weight of the intact betaIG-H3. In normal corneas, only the 68 kD band
was present. Immunohistologically, the antiserum stained corneal subepithelial
regions, including subepithelial deposits, in dystrophic corneas. In normal
corneas, the staining was observed only in the epithelium. These results may
reflect the role of betaIG-H3 in extracellular matrix construction and/or amyloid
formation.
PMID- 9657908
TI - Recovery of corneal nerve morphology following laser in situ keratomileusis.
AB - Morphological changes in the corneal nerves after laser in situ keratomileusis
(LASIK) were investigated and the changes were compared with those observed after
creation of the keratectomy flap without subsequent photoablation. After creating
the hinged flap, a multizone excimer laser photoablation (myopic correction from
6.00 to 6.66 D; diameter 6 mm) was performed on 27 rabbit corneas. Seven of these
27 rabbits received an automated keratectomy without laser photoablation on the
fellow eye. A histochemical acetylcholinesterase reaction was used to demonstrate
the changes in the morphology of the corneal nerves 3 days, 2.5 and 5 months
after the operations. In all specimens the deepest stromal nerve bundles showed
normal morphology. Cut nerve trunks were found at the wound margins and at the
level of the flap interphase in the stromal bed. At 3 days, both epithelial and
basal epithelial/subepithelial nerves were found at the hinge of the flap but the
rest of the flap showed a major loss of epithelial, basal
epithelial/subepithelial and superficial stromal nerves. A few new regenerating
thin nerve fibers were found to emerge from the cut stromal nerve trunks. They
appeared to pass the wound margin into the flap area below the epithelium. At 2.5
and 5 months an increasing number of regenerating nerve leashes were observed to
emerge from the cut stromal nerve trunks. They appeared to send anastomosing
fibers among the neighboring stromal nerves. By this time the epithelial, basal
epithelial/subepithelial and anterior stromal innervation had gained an almost
normal nerve density and architecture. In the corneas with the flap only, the
epithelial innervation was slightly better spared in the center of the flap, and
the stromal changes were somewhat less prominent compared with the LASIK corneas.
PMID- 9657907
TI - Ciliary muscle capillaries have blood-tissue barrier characteristics.
AB - It was determined whether the capillaries in the ciliary muscle are of the blood
tissue barrier or of the permeable non-barrier type. Ciliary body and iris of
normal human and animal eyes were examined by electron microscopy and by
immunohistochemical staining with a panel of antibodies recognizing endothelial
blood-brain barrier markers. In addition, horseradish peroxidase (HRP) tracer
studies of the anterior segment were carried out in rabbits. Our results
demonstrated that the capillary endothelium in human and rabbit ciliary muscle
has few luminal pinocytotic vesicles and a morphological aspect suggesting the
presence of tight junctions. Ciliary muscle and iris capillaries stained positive
for the blood-brain barrier markers Glucose-Transporter-1 and P-Glycoprotein,
while staining for the PAL-E antigen and the transferrin receptor was absent. In
the rabbit ciliary muscle, vascular leakage of exogenous HRP tracer was absent.
It was concluded that this functional barrier and the observed phenotype of
ciliary muscle capillaries are consistent with a blood-tissue barrier function
similar to that of the iris microvasculature.
PMID- 9657909
TI - Expression of sialylated Lewisx gangliosides in cultured lens epithelial cells
from rhesus monkey.
AB - Monkey and human lenses contain essentially the same glycosphingolipids, and
Lewisx and sialylated Lewisx epitopes are expressed on the terminal structure of
neolactotetraosylceramide. However, monolayer cultures of lens epithelial cells
from rhesus monkey expressed gangliosides GM3, GD3 and a small amount of GM1, but
not sialylated Lewisx epitopes. Eight-week-old cultures on various extracellular
matrices resulted in morphological changes in lens epithelial cells. Monolayer of
cells cultured on vitronectin or polylysine assembled into aggregates after 4
weeks of culture. Cells cultured on vitronectin expressed sialyl-Lewisx
gangliosides and did not exhibit GD3. On collagens, fibronectin and laminin
elongated cells were observed in cells cultured for 8 weeks. Thus, the
interaction between cells and extracellular matrices influenced morphology and
glycosphingolipid composition in lens epithelial cells.
PMID- 9657910
TI - The relationship between osmotic stress and calcium elevation: in vitro and in
vivo rat lens models.
AB - Both in vivo and in vitro models were employed in the present study to assess the
relative contribution of osmotic stress and increasing calcium levels to the
development of sugar cataracts. In galactose cataract obtained from galactosemic
weanling rats, the concentration of total calcium increased by nearly 10% at the
first sign of visible opacification observed on the fourth day post-galactose
feeding. After 7 days of galactose feeding, calcium levels continued to rise, to
0.8 mM. During the first 10 days, loss of lens transparency and calcium elevation
was gradual and steady, with precipitous changes occurring on days 11 and 12. In
groups of rats where galactose feeding was stopped after 7 days, cataract
reversal was followed during the next 5 weeks. During the initial first week of
recovery, calcium influx and elevation in the lens continued but began to decline
steadily thereafter. After 3 weeks of recovery, lens transparency had returned to
almost normal. Calcium levels continued to decline and reached normal levels
between day 34 and 42, nearly 4 weeks after removal of the galactose diet. The
relationship between osmotic stress and calcium elevation was investigated more
directly by culturing normal rat lenses in hypoosmotic medium (280 mOsm) to
create osmotic gradients similar to that in galactosemic lenses. The results
showed that during the first day of culture (12 hr), osmotically stressed lenses
gained 3 mg of water, became opaque and gained excess calcium (7 mM compared to
0.7 mM). Microscopic vacuoles appeared to accompany the process of opacification
and contributed to increased light scattering and the loss of lens transparency.
Additional experiments were designed to further distinguish between the effects
of osmotic stress and calcium elevation on the opacification process. Thus,
lenses were incubated in control and high-calcium medium (20 mM) at 300 mOsm.
Within 12 hr of incubation, calcium elevation progressed to 1.37 mM, nearly
doubling the normal value. Although opacification was observed in these lenses,
no sign of vacuoles was evident. Collectively, the findings from this study
support the premise that an early influx of calcium is brought about by osmotic
stress and is responsible for the observed loss in transparency in osmotic
(sugar) cataract.
PMID- 9657911
TI - Temperature-sensitive interactions between RPE and rod outer segment surface
proteins.
AB - Phagocytosis of rod outer segments by the retinal pigment epithelium is
distinguished by the two distinct temperature-dependent steps of binding and
ingestion. This study was designed to see if retinal pigment epithelial (RPE)
plasma membrane proteins interact with ROS plasma membrane proteins at
temperatures favoring either binding or ingestion. A modified blot overlay assay
was used whereby Western blots of RPE plasma membrane proteins were overlaid with
biotinylated ROS plasma membrane proteins. RPE/ROS interactions were detected by
streptavidin-HRP and the ECL method at 25 degrees C (ingestion), 15 degrees C
(binding), and 4 degrees C (little or no binding or ingestion). Unlabeled ROS
proteins served as the negative control. Competition with excess unlabeled ROS
proteins were used to test the specificity of the protein interactions. Some
protein interactions were somewhat temperature dependent. For example, two RPE
plasma membrane proteins (200 kDa and 173 kDa) interacted with ROS plasma
membrane proteins at both 25 degrees C and 15 degrees C, but not at 4 degrees C.
A strongly labeled protein at 50 kDA protein was present at 25 degrees C but
weakly labeled at 15 degrees C and at 4 degrees C. Other protein interaction were
more clearly temperature dependent. For example, a 110 kDa RPE protein interacted
with ROS proteins only at 25 degrees C. Another RPE protein (55 kDa) interacted
only at 15 degrees C. These latter data provide correlations between binding
events in the assay and previously described stages of phagocytosis.
PMID- 9657912
TI - Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF.
AB - We employed a morphological assay of outer segment collapse to determine if
growth factors or other supplements directly affect dissociated rod
photoreceptors in vitro. The morphological changes in outer segments were
correlated with the light responsiveness of rods. Time-lapse video microscopy was
used to observe the collapse of rod outer segments from isolated single cells and
small clumps of cells. A consistent pattern of outer segment collapse into the
inner segment was observed, yielding a convenient assay of the effects of
neurotrophic factors on photoreceptor functional maintenance. The functional
state of rods, defined as light-responsiveness, was measured with suction
electrode recordings and matched with the various stages of outer segment
collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived
neurotrophic factor (GDNF) at a high concentration, yielded statistically
significant improvements in rat outer segment survival times. Basic fibroblast
growth factor (bFGF), which rescues photoreceptors in several rodent models of
retinal degeneration, produced a significant increase in survival time in the
presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF
also yielded a significant increase in survival times. When brain-derived
neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times
did not change. Outer segments collapsed more quickly when either pigment
epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal)
were present. Our results show that rod photoreceptors can respond to bFGF, GDNF
and CNTF in vitro and provide evidence for a direct effect of these neurotrophic
factors on rods. The rapid collapse of isolated photoreceptors in this model
provides a convenient means for testing various neurotrophic agents and the
induced cellular responses.
PMID- 9657913
TI - Serum-free media for culturing and serial-passaging of adult human retinal
pigment epithelium.
AB - The ability of a chemically-defined serum-free culture medium to support the
attachment, growth and serial passaging of primary adult human retinal pigment
epithelial (RPE) cells was studied. Primary cultures of adult human RPE were
established in a chemically-defined serum-free culture medium on both bare or
bovine corneal endothelial extracellular matrix-coated tissue-culture plastic.
Confluent cells were serially passaged in chemically-defined serum-free culture
medium three times by trypsinization, and trypsin activity was quenched with
aprotinin. First passage RPE cells were plated onto tissue-culture plastic
precoated with bovine corneal endothelial extracellular matrix or uncoated tissue
culture plastic in 24 well plates at a density of 50 viable cells mm-2. Cells
were maintained either in chemically-defined serum-free culture medium, DMEM
without serum, or DMEM with 15% fetal bovine serum. For each medium plating,
efficiencies were determined 24 hours after plating, and growth rates were
determined on the first, third and seventh days after plating. Morphometric image
analysis was performed on cells cultured for up to 6 weeks and three serial
passages. Seeding efficiency on bovine corneal endothelial extracellular matrix
coated tissue-culture plastic and treated tissue-culture plastic were higher for
chemically-defined serum-free culture medium (88.9+/-2.7% and 47.1+/-4.1%,
respectively) and DMEM with serum (87.2+/-5.6% and 52.9+/-10.5%, respectively)
than DMEM without serum (59.2+/-5.6% and 33.1+/-6.9%, respectively; P<0.01). The
RPE proliferation rate in chemically-defined serum-free culture medium was
comparable to DMEM with serum on both substrates within the first 3 days,
although cells in DMEM with serum had a higher proliferation rate on day 7. Cells
cultured in DMEM without serum, eventually decreased in number. RPE maintained in
chemically-defined serum-free culture medium maintained a consistent
proliferation rate, reached confluence, and retained an epitheloid morphology on
either extracellular matrix or tissue-culture plastic for up to 6 weeks and three
serial passages. Primary RPE reached confluence at 12+/-3 days on bovine corneal
endothelial extracellular matrix-coated tissue-culture plastic and 21+/-5 days on
treated tissue-culture plastic. Confluent cultures were composed of small
hexagonal cells with epitheloid morphology on both substrates. We concluded that
primary adult human RPE can be cultured in this chemically-defined serum-free
culture medium. RPE will proliferate, reach confluence, retain their epitheloid
morphology and can be serially passaged in the absence of serum.
PMID- 9657914
TI - Light stimulates tyrosine phosphorylation of rat rod outer segments In vivo.
PMID- 9657915
TI - Announcements
PMID- 9657916
TI - Index
PMID- 9657918
TI - 10th International Congress of Immunology.
AB - Copyright
PMID- 9657917
TI - Retractions.
PMID- 9657919
TI - Multifunctional cytokine expression by human coronary endothelium and regulation
by monokines and glucocorticoids.
AB - Human endothelium is capable of expressing a variety of molecules, including
cytokines and growth factors, critical to inflammation. This aspect of coronary
endothelium has not been studied in detail. In this study, we report, for the
first time, expression of multifunctional cytokines by human coronary artery
endothelial cells (HCAEC) and their regulation by inflammatory cytokines and
glucocorticoids. We also compared expression of cytokine transcripts in two
additional cell lines derived from pulmonary artery (HPAEC) and umbilical vein
(HUVEC) endothelium. HCAEC expressed transcripts for interleukin 5 (IL-5), IL-6,
IL-8, and monocyte chemotactic protein-1 (MCP-1) constitutively. Induction of IL
1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and MCP
1 was seen following treatment with TNFalpha. We found no expression of IL-1RA,
IL-2, IL-4, IL-13, TNF-alpha, or IFN-gamma in HCAEC. IL-1beta and TNF-alpha
synergistically induced IL-6 and GM-CSF and additively induced IL-8 and MCP-1
production, while IL-2, IL-10, IFN-alpha, and IFN-gamma had little or no
additional effects. Interestingly, no IL-1alpha or IL-5 protein product was found
even after maximal stimulation of HCAEC. No significant differences were seen in
the profile of cytokine genes expressed by HCAEC, HPAEC, or HUVEC.
Glucocorticoids inhibited IL-8 production from all three cell lines. This study
demonstrates that human coronary endothelial cells are capable of expressing a
wide variety of multifunctional cytokines which may be of relevance to vascular
inflammation.
PMID- 9657920
TI - A novel assay of angiogenesis in the quail chorioallantoic membrane: stimulation
by bFGF and inhibition by angiostatin according to fractal dimension and grid
intersection.
AB - In a novel assay of angiogenesis in the quail chorioallantoic membrane (CAM), we
measured vascular pattern and angiogenic rate after homogeneous exposure of the
entire vascular tree to recognized modulators of vessel growth. In comparison to
phosphate-buffered saline (PBS)-treated controls, the vascular stimulator, basic
fibroblast growth factor (bFGF or FGF-2), increased the rate of angiogenesis by a
maximum of 72%, whereas a recently discovered angiogenic inhibitor, angiostatin,
decreased the rate of vascular growth by a maximum of 68%. The perturbants were
applied in PBS to the CAM of 7-day-old embryos (E7) cultured in petri dishes, and
the embryos were cultured further until fixation at E8 or E9. For morphometry of
the quasi-two-dimensional CAM vasculature, digital images of arterial endpoints
from the middle region of the CAM were acquired in grayscale at a magnification
of 10x, binarized to black/white, and skeletonized. The pattern of vessel
branching was assessed by measurement of the fractal dimension (Df), and vessel
density (rhov), with the method of grid intersection. Correlations between these
two statistical techniques were linear (r2 ranged from 0.967 to 0.985). For
skeletonized images at E9, Df and rhov of bFGF-treated samples were 1.55 +/- 0.01
and 782 +/- 26/cm2, respectively (relative to 1.49 +/- 0.02 and 583 +/- 60/cm2
for controls), and of angiostatin-treated samples, 1.43 +/- 0.02 and 424 +/-
74/cm2 (relative to 1.50 +/- 0.02 and 616 +/- 59/cm2 for controls). To establish
normalization values for rates of angiogenesis, we analyzed untreated CAMs of E6
to E12. From E7 to E10 in skeletonized images, Df increased linearly from 1.37 +/
0.01 to 1.54 +/- 0.01 and rhov from 311 +/- 67 to 746 +/- 124/cm2 (in both
cases, r2 = 1.000). Thus, the rates of normal angiogenic growth as measured by Df
and rhov were 0.06/day and 138/cm2-day, respectively. From E10 to E12, Df and
rhov declined slightly. Differences between the vasculature of untreated and PBS
treated CAMs were statistically insignificant. In conclusion, vascular branching
pattern and density in the quail CAM were stimulated by bFGF and inhibited by
angiostatin. We quantified these changes with statistical significance by Df and
rhov, which are expressed relative to the rates of normal developmental
angiogenesis measured for the two parameters in untreated quail embryos.
PMID- 9657921
TI - Ultrastructural study on the venous sphincter in the sublobular vein of the
canine liver.
AB - Although the existence of venous sphincters has been demonstrated in the
sublobular veins of the canine liver, the role it plays in the regulation of
liver blood flow is still uncertain. In the present study, I examined the fine
structures of the venous sphincters treated with four kinds of drugs
(epinephrine, histamine, isoproterenol, and histamine releaser) by conventional
electron microscopy and by scanning electron microscopy using microvascular
corrosion casts. Intravenous administration of epinephrine, histamine, and
histamine releaser (compound 48/80) resulted in a strong constriction at the
small branches (100-400 micron in caliber) of the sublobular veins, while the
treatment with isoproterenol showed dilatation in the same branches. When treated
with compound 48/80, both the endothelial-specific granules (Weibel-Palade
granules) and the mast cell's granules of the sublobular veins showed swelling
and became transparent reducing electron density. In contrast, the shape and
electron density of the granules did not change when the veins were dilated. The
results suggest that the small branches of the sublobular veins have extremely
important functions for the regulation of the liver blood flow under normal
conditions and that the component parts in the Weibel-Palade granules and/or mast
cell's granules may be involved in the constriction of the sphincter muscles.
PMID- 9657922
TI - Direct in vivo measurement of gastric microvascular pressures in the rat.
AB - There are no direct data available on micropressures in the gastric
microcirculation in spite of its pivotal role in the development of acute gastric
mucosal lesions. Our goal was to develop an in vivo method to directly measure
intravascular pressure and vessel diameter in various gastric microvessels. This
paper describes methods and procedural details of our novel preparation of the
exteriorized rat stomach for vascular micropuncture studies. The stomach of the
anesthetized rat was fixed with minimal surgery in a temperature-controlled
gastric chamber. Two preparations were used, both from the serosal side: a
seromuscular preparation to study the circulation of superficial outer muscular
layers and a submucosal preparation-following careful dissection of the
seromuscular layer-to study the submucosal and deeper mucosal microcirculations.
Intravascular hydrostatic pressure was measured with a servo-null micropressure
measuring system, while vessel diameter was evaluated on the television screen
with videometry. Data (average +/- SE) were obtained from muscular arterioles
(20.8 +/- 0.93 micron; 29.8 +/- 1. 32 mmHg), venules (23.4 +/- 1.61 micron; 18.1
+/- 0.61 mmHg), submucosal arterioles (50.9 +/- 3.55 micron; 55.4 +/- 2.78 mmHg),
venules (53.7 +/- 2.06 micron; 21.4 +/- 0.73 mmHg), and deeper mucosal arterioles
(20.2 +/- 1.06 micron; 33.8 +/- 0.81 mmHg), venules (29.9 +/- 1.17 micron; 25.8
+/- 0.47 mmHg), at a systemic arterial pressure of 110 +/- 2.4 mmHg (n = 10 each
from 14 animals). Further experiments demonstrated the applicability of this
method to examine the effects of systemic blood pressure reduction and local
application of vasoactive agents on the gastric microcirculation. This method is
useful for analyzing the microcirculation of the stomach in vivo under different
experimental conditions.
PMID- 9657924
TI - Can low density lipoprotein influence microvascular caliber?
AB - The intracellular free calcium concentration ([Ca2+]i) plays an important role in
the regulation of vascular tone. In vascular smooth muscle cells (VSMCs) LDL
causes changes in vascular tone by increasing [Ca2+]i. Pericytes are regarded as
the microvascular counterpart of VSMCs and implicated in the regulation of
microvascular cell biology under normal and pathological conditions (e.g.,
diabetes mellitus, arterial hypertension, arteriosclerosis). For this reason
pericytes and VSMCs were compared in their ability to increase [Ca2+]i after
stimulation with LDL. Single VSMCs and pericytes were loaded with 2 microM of the
Ca2+-sensitive dye Indo-1/AM. Fluorescence was recorded at 405 nm (Ca2+-bound)
and 485 nm (Ca2+-free). Cells in suspension were loaded with 2 microM of the
calcium ionophore FURA-2 AM (excitation wavelengths: 340 and 380 nm, emission 505
nm). Basal [Ca2+]i levels were significantly higher in single pericytes (165 +/-
38 nmol/L, n = 41) than in VSMCs (150 +/- 39 nmol/L, n = 40, P = 0.0038). In cell
suspensions the following values were obtained: Pericytes (113 +/- 27 nmol/L, n =
36) and VSMCs (109 +/- 26 nmol/L, n = 28), which are statistically not
significant. For all concentrations of LDL used (except at 1 microg/ml n-LDL),
the increase above basal values was significant and both cell types showed a
clear dose-dependent reaction pattern. This study shows for the first time that
pericytes and VSMCs increase their [Ca2+]i in a similar way after LDL
stimulation. In analogy to aortic smooth muscle cells, our results indicate that
LDL mediated [Ca2+]i changes in pericytes in the microvascular bed may cause
vasoconstriction leading to impairment of blood flow in the microvasculature.
PMID- 9657923
TI - In vivo neutralization of P-selectin inhibits leukocyte-endothelial interactions
in retinal microcirculation during ocular inflammation.
AB - P-selectin is one of the adhesion molecules involved in leukocyte rolling during
an inflammatory reaction. The aim of this study was to examine the role of P
selectin in leukocyte-endothelial interactions in retinal microcirculation during
ocular inflammation, known as endotoxin-induced uveitis (EIU), in vivo. EIU was
induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). At the
time of LPS treatment or 12 h later, anti-rat P-selectin mAb (ARP) was injected
intravenously, and its effect on leukocyte behavior in the retina was studied
after intravital staining with acridine orange using a scanning laser
ophthalmoscope. P-selectin gene expression in the retina was also studied by a
semiquantitative polymerase chain reaction (PCR) method. Administration of ARP at
the time of LPS treatment significantly reduced the number of rolling leukocytes
at 6 and 12 h by 68% (P < 0.05) and 83% (P < 0.01), respectively, and the number
of cells infiltrating the vitreous at 48 h by 61% (P < 0.05). Interestingly, ARP
significantly inhibited the vasodilation observed during EIU. In contrast,
delayed administration of ARP blocked neither cellular infiltration nor
vasodilation. P-selectin gene expression was upregulated during the course of
EIU. In conclusion, P-selectin may significantly contribute to the development of
inflammation in the early stage of endotoxin-induced ocular inflammation.
PMID- 9657925
TI - A comparison of the microcirculation in the rat spinotrapezius and diaphragm
muscles.
AB - Of all skeletal muscles examined in the rat, the spinotrapezius (S) and diaphragm
(D) have the closest fiber-type composition. However, their oxidative capacities
differ by two- to threefold. We have developed an intravital microscopy
preparation to study diaphragm microcirculation in vivo. Using this preparation
and the standard spinotrapezius model first described by S. D. Gray (1973,
Microvasc. Res. 5, 395-400), we tested the hypothesis that pronounced
microcirculatory differences would exist between these two muscles as a function
of their disparate oxidative capacities. The lineal density of all capillaries in
the spinotrapezius was 33.6 +/- 1.5 compared to 65.1 +/- 3.3 capillaries/mm in
the diaphragm (P < 0.001). In the diaphragm compared with the spinotrapezius
muscle, a significantly (P < 0.05) greater proportion of capillary countercurrent
flow (D, 29 +/- 6% vs 8 +/- 6%) existed. Within both muscles, there was a similar
proportion of capillaries supporting red blood cell (RBC) flow (S, 89 +/- 7% vs
D, 92 +/- 2%). However, the diaphragm supported significantly (P < 0.001) greater
intracapillary RBC velocities (D, 302 +/- 11 vs S, 226 +/- 9 micron/s) and fluxes
(D, 33.4 +/- 1.1 vs S, 19.2 +/- 2.1 cells/s) compared with the spinotrapezius.
Capillary "tube" hematocrit was greater (P = 0.01) in the diaphragm (0.32 +/-
0.02) than in the spinotrapezius (0.22 +/- 0.03) muscle. These data demonstrate
that microcirculatory flow characteristics in resting muscle can be regulated
independent of muscle fiber-type composition and may be related to muscle
oxidative capacity.
PMID- 9657926
TI - Growth factors reverse the impaired sprouting of microvessels from aged mice.
AB - Aging is accompanied by impaired angiogenesis and deficient expression of several
angiogenic growth factors. To test the hypothesis that replacement of these
factors would improve angiogenesis in aged animals, we cultured microvessels
derived from the epididymal fat pad of aged and young mice ("aged" and "young"
microvessels) in three-dimensional collagen gels for 2 weeks and measured their
sprouting (formation of branch points) in response to fetal bovine serum (FBS),
endothelial cell growth supplement (ECGS), and the specific growth factors
transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor
(VEGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor
(bFGF). In the presence of culture medium with 1% FBS (Minimal medium), sprouting
of aged microvessels was significantly less than sprouting of young microvessels.
The addition of high levels of FBS and ECGS to Minimal medium enhanced the
sprouting of microvessels from aged mice to a greater degree than that of young
mice, such that the difference between the two age groups was no longer
significant. Formation of branch points by aged microvessels was also
significantly increased by Minimal medium supplemented with TGF-beta1, bFGF, IGF
1, or VEGF (listed in order of highest to lowest stimulation). Sprouts generated
in the presence of VEGF possessed a particularly high percentage of endothelial
cells. Mitomycin C did not diminish the degree of sprouting induced by TGF-beta1,
VEGF, or IGF-1, a result indicating that early stages of angiogenesis, including
formation of branch points, do not require cell division. From our findings in
vitro, we propose that age-related deficiencies in angiogenesis in vivo are
likely to be due, in part, to a decrease in angiogenic growth factors in the
extracellular milieu.
PMID- 9657927
TI - Factor V Leiden, mild hyperhomocyst(e)inemia and Buerger's disease.
PMID- 9657929
TI - Initiation of DNA replication in phages and plasmids-a workshop summary.
AB - Recent progress in understanding initiation mechanisms of DNA replication was
discussed by some 30 speakers from Europe and U.S.A. in a workshop funded
entirely by the Juan March Foundation of Madrid. Several speakers were
postdoctoral associates and were selected from poster presenters. This was
probably the first meeting at which phage and plasmid systems were given top
billing together. The confluence was highly successful because of considerable
overlap in strategies employed by the two systems. Mechanistic studies on DNA
replication started with phage and the lessons learned have guided the thinking
on eukaryotic DNA replication (Stillman, J. Biol. Chem. (1994) 269, 7047). The
research on bacterial plasmids has also been pioneering in defining the
principles of initiation control and has unraveled novel biological regulatory
mechanisms such as antisense control.
PMID- 9657930
TI - Genetic elements of Bacteroides species: a moving story.
PMID- 9657931
TI - Kinetics of conjugative transfer: a study of the plasmid pXO16 from Bacillus
thuringiensis subsp. israelensis.
AB - The aggregation-mediated conjugation system of Bacillus thuringiensis subsp.
israelensis, encoded by the 200-kb plasmid pXO16, is highly potent in
transferring itself and efficient in mobilizing other nonconjugative plasmids.
The present study reveals some salient features of this conjugation system. Our
observations can be summarized as follows: (i) The conjugative transfer takes
about 3(1/2) to 4 min. For a 200-kb plasmid this corresponds to about 1 kb per
second. (ii) The ability to transfer the plasmid seems to be evenly distributed
among the donors. (iii) Functionally, the mating complex was found to consist of
one donor and one recipient cell, even though aggregates comprising thousands of
interconnected cells are formed. (iv) Having donated the plasmid, the donor needs
a "period of recovery" of about 10 min before it can redonate the plasmid. (v)
Secondary transfer, i.e., transfer from newly formed transconjugants, is delayed
about 40 min. This maturation time exceeds the generation time, and it may
indicate that to display donor activity, a surface protein (the aggregation
substance) has to be uniformly incorporated into the cell wall. Lastly, we found
that when the experiments were sufficiently short and when the recipient cells
were in excess compared with the donors, the process of conjugation could be
reasonably described by a kinetic model analogous to the Michaelis-Menten model
for enzyme catalysis. This allowed us to estimate (vi) the maximal conjugation
rate to be about 0.05 transconjugant per donor per minute, and (vii) the Km
value, i.e., the concentration of recipient that results in half of the maximal
conjugation rate, to be about 4 x 10(6) recipients/ml.
PMID- 9657932
TI - Characterization of a novel insertion sequence, IS1194, in Streptococcus
thermophilus.
AB - A novel insertion sequence, IS1194, has been identified in the lactic acid
bacterium Streptococcus thermophilus CNRZ368. This 1200-bp element has 16-bp
imperfect terminal inverted repeats. The single large open reading frame of this
element encodes a 332-amino-acid protein that displays similarities with
transposases encoded by bacterial insertion sequences belonging to the IS5 group
of the IS4 family. A single copy of IS1194 was detected by hybridization in only
2 of the 19 S. thermophilus strains tested and in 4 of the 13 Lactococcus lactis
strains investigated. This suggests that this IS element was acquired by
horizontal transfer. The unique IS1194 copy of S. thermophilus CNRZ368 is located
in a region of at least 12 kb that was probably acquired by horizontal transfer
from L. lactis. Furthermore, the IS1194 right end is identical to sequences found
in a broad-host-range conjugative plasmid from Streptococcus pyogenes, pSM19035.
PMID- 9657933
TI - Sequence analysis of plasmid pTF5, a 19.8-kb geographically widespread member of
the Thiobacillus ferrooxidans pTFI91-like plasmid family.
AB - The most important features of plasmid pTF5, a 19,793-bp plasmid that was
isolated from Thiobacillus ferrooxidans ATCC33020, are presented. The plasmid
contained at least 14 complete open reading frames (ORFs), most of which had
clear amino acid sequence similarity to previously identified proteins. The
majority of ORFs were related to proteins commonly found on plasmids such as
replication-, partition-, and stability-associated proteins or on transposons
such as transposases, an invertase, and a resolvase. Products of three of the
ORFs were related to redox-active proteins and possibly constitute an electron
transport system. Plasmids with restriction endonuclease maps identical to that
of pTF5 have been widely reported among T. ferrooxidans strains, and in this
study, pTF5 was itself shown to be a member of the widely distributed pTFI91 T.
ferrooxidans plasmid family. A comparison of restriction endonuclease maps
indicated that a pTFI91-like plasmid (9.8 kb) appeared to be contained entirely
within pTF5.
PMID- 9657934
TI - Identification of linear DNA plasmids of the yeast Pichia pastoris.
AB - Two DNA plasmids, approximately 11 and 8 kb in size, have been identified in a
strain of the yeast Pichia pastoris (Northern Regional Research Laboratories No.
Y4290). The plasmids are resistant to RNase A and lambda exonuclease, but are
sensitive to digestion by DNase I, suggesting that they are linear and double
stranded DNA with 5'-protected ends. A restriction map has been constructed for
the 11-kb plasmid, confirming that it is linear.
PMID- 9657935
TI - Structural and functional properties of the hsp16.4-bearing plasmid pER341 in
Streptococcus thermophilus.
AB - The plasmid pER341 (2798 bp) of Streptococcus thermophilus ST134 was sequenced
and its open reading frame (ORF) regions were characterized. Analysis of
nucleotide sequences showed the putative translation product of ORF1 (rep)
sharing a high level of homology with replication proteins of several small
plasmids present in lactic acid bacteria and staphylococci. This and homology of
regions of plus-strand (ORI) and minus-strand (ssoA) origin of replication with
pC194-class plasmids indicated that pER341 replicates by the rolling-circle
mechanism. ORF2 corresponded to a putative hsp gene that apparently encodes
Hsp16.4, a 142-amino-acid heat stress protein. Hsp16.4 shared significant
identity with other small, 18-kDa-class heat stress proteins from prokaryotic and
eukaryotic sources. Hsp16.4 is apparently the first plasmidborne low-molecular
weight heat stress protein reported in dairy fermentation bacteria with a
potential role in temperature-regulated functions in S. thermophilus.
PMID- 9657936
TI - Involvement of a 120-MDa plasmid of Azospirillum brasilense Sp245 in the
production of lipopolysaccharides.
AB - Using Omegon-Km mutagenesis, six Azospirillum brasilense Sp245 mutant derivatives
lacking the capability to synthesize either one of the two major O-specific
polysaccharides (O-PSs) were constructed in vivo. In all of the Lps mutants
obtained, single Omegon-Km insertions were shown to be located on an indigenous
plasmid DNA with molecular weight 120 MDa (p120). Physical and immunochemical
analyses revealed two p120 loci coding for O-PSI and two p120 loci involved in
the production of O-PSII. One of the lps loci from both groups was also shown to
act in the production of Calcofluor-binding polysaccharides. It was demonstrated
that two Sp245 plasmid bands with apparent molecular weights of 120 and 130 MDa
(as visualized by analytical gel electrophoreses) seem to be the two topological
forms of the same plasmid species (p120). Transfer properties of p120 were also
examined.
PMID- 9657937
TI - A plasmid family containing two different expression cassettes suitable for
immunomodulation and genetic immunization.
AB - We have developed an improved eukaryotic expression vector that consists of two
distinct, complete, and differentially regulated transcription units. The
peculiarities of this prototype vector, named pRC110, are represented by two
different strong promoter/enhancer sequences, cytomegalovirus and Rous sarcoma
virus, that independently drive transcription of two recombinant cDNAs, which may
be easily cloned into specific rare restriction sites. Moreover, we describe a
simple way to introduce an optimal translational start site context 5' to any
peptide to be cloned in our vectors, thus allowing the correct and efficient
expression of even a single part of a larger gene or a short synthetic peptide
lacking its own AUG and neighboring regions. We demonstrate the in vivo
expression efficacy of pRC110 for use in genetic vaccination through direct
intramuscular gene transfer: specific antibodies are raised against one of the
encoded peptides 3 weeks after muscle injection, and efficient transcription of
the other syngeneic cDNA, mouse interleukin-2, is shown. The development of a
"family" of vectors directly deriving from pRC110 is also described, with the
common property that one of the encoded proteins may modulate the effects of the
other. We recommend the use of pRC110 for genetic immunization and immunological
response studies, when the concomitant local production of an immunogenic peptide
and of a syngeneic immunomodulating cytokine is required.
PMID- 9657938
TI - Retroviral matrix proteins: a structural perspective.
PMID- 9657939
TI - Characterization of the thermosensitive ts453 reovirus mutant: increased dsRNA
binding of sigma 3 protein correlates with interferon resistance.
AB - The mutation harbored by the reovirus ts453 thermosensitive mutant has been
assigned to the S4 gene encoding the major outer capsid protein sigma 3. Previous
gene sequencing has identified a nonconservative amino acid substitution located
near the zinc finger of sigma 3 protein in the mutant. Coexpression in COS cells
of the sigma 3 protein presenting this amino acid substitution (N16K), together
with the other major capsid protein mu 1, has also revealed an altered
interaction between the two proteins; this altered interaction prevents the sigma
3-dependent cleavage of mu 1 to mu 1C. This could explain the lack of outer
capsid assembly observed during ts453 virus infection at nonpermissive
temperature. In the present study, we pursued the characterization of this mutant
sigma 3 protein. Although the N16K mutation is located close to the zinc finger
region, it did not affect the ability of the protein to bind zinc. In contrast,
this mutation, as well as mutations within the zinc finger motif itself, can
increase the binding of the protein to double-stranded RNA (dsRNA). It also
appears that the N16K mutant protein is more efficiently transported to the
nucleus than the wild-type protein, an observation consistent with the postulated
role of dsRNA binding in sigma 3 nuclear presence. The lack of association with
mu 1, and/or the increased dsRNA-binding activity of sigma 3, could be
responsible for a partial resistance of the ts453 virus to interferon treatment
and this could have important consequences in the context of protein synthesis
regulation during natural reovirus infection.
PMID- 9657940
TI - Sulfatide inhibits HIV-1 entry into CD4-/CXCR4+ cells.
AB - Sulfatide (3'sulfogalactosylceramide) is the natural sulfated derivative of
galactosylceramide (GalCer), a glycosphingolipid receptor allowing HIV-1
infection of CD4-negative cells from neural and intestinal tissues. The
incorporation of exogenous sulfatide into the plasma membrane of HT-29 (a CD4
/GalCer+/CXCR4+ human intestinal cell line) or RD (CD4-/GalCer-/ CXCR4+ human
rhabdomyosarcoma) resulted in a dose-dependent inhibition of HIV-1 infection.
Experiments with luciferase reporter viruses pseudotyped with HIV-1 or
amphotropic murine leukemia virus envelopes demonstrated that sulfatide acts at
the level of viral entry. Paradoxically, the transfer of sulfatide in the plasma
membrane of various CD4- cells resulted in increased binding of HIV-1. Surface
pressure measurements were conducted to study the interaction of gp120 with
glycosphingolipid monolayers. The data showed that gp120 could penetrate into a
monomolecular film of GalCer, confirming the role of this glycosphingolipid as a
functional receptor for HIV-1. In contrast, the insertion of gp120 into a
monolayer of sulfatide was very limited. Moreover, the incorporation of sulfatide
in a monomolecular film of GalCer specifically inhibited the penetration of
gp120. In conclusion, these data show that sulfatide mediates gp120 binding but,
in marked contrast with GalCer, is not able to initiate the fusion event.
PMID- 9657941
TI - Characterization of cucumber mosaic virus. V. Cell-to-cell movement requires
capsid protein but not virions.
AB - To ascertain the importance of amino-terminal proximal capsid protein (CP)
sequences in cel-to-cell movement, virion formation, and stabilization, two CP
mutants of cucumber mosaic virus (CMV) were generated by deletion of sequences
encoding CP amino acids 15-40 (delta Sal-Nru) or 26-40 (delta Sac-Nru). Wildtype
CMV and CMV containing delta Sac-Nru could infect systemically four host species,
although symptoms induced by the two viruses usually were different CMV
containing delta Sal-Nru could only infect Nicotiana benthamiana and N.
clevelandii systemically, but only slowly, suggesting phloem-independent long
distance movement. A variant mutant designated delta Sal-Nru* could systemically
infect N. tabacum as well as the above two Nicotiana species, rapidly, but could
not systemically infect Cucurbita pepo. Virus particles could not be detected in
plants infected by delta Sal-Nru, while delta Sal-Nru* and delta Sac-Nru formed
particles of lower stabilities than for wildtype virus. The CPs of delta Sal-Nru
and delta Sal-Nru* could bind RNA in vitro, although less strongly than delta Sac
Nru or wildtype CMV. These data indicate that amino-terminal proximal sequences
of the CMV CP interact with viral RNA and are required for the formation of
stable virions. Moreover, while the CP is necessary for cell-to-cell movement,
the ability to form virions is not a prerequisite for cell-to-cell movement.
PMID- 9657942
TI - Impaired activation and binding of the erythropoietin receptor by a mutant gp55
of Friend spleen focus-forming virus, which has a cytoplasmic domain.
AB - A murine erythroleukemogenic retrovirus, Friend spleen focus-forming virus,
encodes an envelope protein-like membrane glycoprotein (gp55) in its defective
env gene which is responsible for activation of the erythropoietin receptor
(EpoR) and the abnormally rapid proliferation of erythroid precursor cells. The
S34 mutant gp55, which possesses an additional cytoplasmic domain, is
nonpathogenic and its processing to the cell surface is severely reduced compared
to that of the wild-type gp55. In this study, we found that the S34 mutant gp55
neither binds to nor activates the EpoR. The S34 mutant gp55 formed disulfide
bonded homodimers in the rough endoplasmic reticulum (RER) membrane much less
efficiently than the wild-type gp55, which is consistent with the proposal that
homodimer formation is a prerequisite for gp55 to be exported from the RER. We
found that the wild-type gp55 that is bound to EpoR in the RER consists of a
large number of monomers and a small number of dimers, suggesting that monomers
of the S34 mutant gp55 have lost the ability to bind to the EpoR. The 1-bp
insertion present in the wild-type gp55 gene, causing a loss of the cytoplasmic
domain, is essential for pathogenicity in that it renders the encoded protein
capable of both binding to the EpoR and transport to the cell surface.
PMID- 9657943
TI - The polyvalent staphylococcal phage phi 812: its host-range mutants and related
phages.
AB - Ninety-five percent of 782 culture collection strains, as well as hospital
strains of Staphylococcus aureus subsp. aureus of different provenance and 43% of
89 culture collection strains of different coagulase-negative species of the
genus Staphylococcus, were found to be sensitive to the polyvalent phage phi 812
or to at least one of its host-range mutants or to the polyvalent phages SK311,
phi 131, and U16. Thus sensitivity to the polyvalent staphylococcal phages seems
to be one of the common features of S. aureus subsp. aureus strains. The
adsorption kinetics and one-step growth characteristics of the phages phi 812 and
SK311 were estimated. Restriction genomic maps of the phages phi 812 (146.5 kb)
and SK311 (141.1 kb) were constructed by use of the restriction endonucleases
AvaII, PstI, KpnI, SacI, SmaI, and XhoI. The host-range mutations of the phage
phi 812 were localized on this map. Comparison of restriction patterns of the
phages phi 812 and SK311 with those of the polyvalent phages U16 and phi 131
suggests that all these phages are closely related. Their genomes differ from
each other mostly by some deletions, insertions (1-3 kb), or inversions. Evidence
was given that the phage phi 812 together with SK311, phi 131, and U16 belongs in
the phage species Twort, the description of which is substantially supplemented
with the data on the phage phi 812 reported in this paper.
PMID- 9657944
TI - Evidence that the RNA methylation and poly(A) polymerase stimulatory activities
of vaccinia virus protein VP39 do not impinge upon one another.
AB - Vaccinia protein VP39 has two RNA modifying activities. In monomeric form, it
acts as an mRNA cap-specific 2'-O-methyltransferase, specifically modifying the
ribose moiety of the first transcribed nucleotide of m7G-capped mRNA. In
association with VP55, the catalytic subunit of the vaccinia poly(A) polymerase,
VP39 facilitates the rapid elongation of poly(A) tails that are already greater
than approximately 35 nt in length. Introducing new assays, we provide evidence
that substrates for each of VP39's two activities do not detectably modulate the
converse reaction and that VP39's 2'-O-methyltransferase activity is not
significantly affected by its association with VP55. In an electrophoretic
mobility shift assay, VP39 interacted with a short (5 nucleotide) RNA only when
the latter was m7G-capped. Complexes with longer (22 nucleotide) RNAs were more
stable (i.e., cap-independent) but were further stabilized by the presence of an
m7G cap. An additional complex was observed at elevated RNA:protein molar ratios,
indicating the presence of two RNA binding sites per VP39 molecule. Interaction
at one of these sites was stabilized by the cap structure. Additional experiments
indicated that RNA molecules undergoing poly(A) tail elongation by the VP55-VP39
heterodimer are not favored as cap-methylation substrates.
PMID- 9657945
TI - Pleiotropic effects of HIV-1 protein R (Vpr) on morphogenesis and cell survival
in fission yeast and antagonism by pentoxifylline.
AB - Expression of HIV-1 Vpr causes cell cycle G2 arrest, change in cell shape, and
cell death over a large evolutionary distance ranging from human to yeast cells.
As a step toward understanding these highly conserved Vpr functions, we have
examined the effect of Vpr on cytoskeletal elements and the viability of fission
yeast. We demonstrate that the changes in cell morphology induced by Vpr in
fission yeast are caused by several underlying cellular abnormalities, including
increased biosynthesis of chitin in the cell wall, disruption of the actin
cytoskeleton, and altered polarity for cell growth. The extent of these cellular
alterations and cell survival correlates with the level of vpr expression.
Accompanying cell death, Vpr induces aberrant nuclear morphologies in fission
yeast which are similar to those found during the apoptosis induced by Vpr in
mammalian cells. The Vpr-induced cytopathic effects and cell death can be
suppressed by treatment with pentoxifylline, a compound that inhibits HIV-1 viral
replication and suppresses Vpr-induced cell cycle G2 arrest in human and fission
yeast cells. The results presented here suggest that pentoxifylline suppresses
the effects of Vpr by blocking interactions of Vpr with cellular proteins. Given
that pentoxifylline has potential therapeutic value in blocking the effects of
Vpr in HIV-infected patients, understanding the molecular mechanisms by which
pentoxifylline antagonizes Vpr may have general implications for HIV therapy.
PMID- 9657946
TI - Two new human T-lymphotropic virus type I phylogenetic subtypes in
seroindeterminates, a Mbuti pygmy and a Gabonese, have closest relatives among
African STLV-I strains.
AB - Six new HTLV-I strains from seroindeterminate individuals were analyzed: four
from Gabon, one from a Mbuti Efe pygmy in Congo (formerly Zaire), and one from a
Congolese patient residing in Belgium. The LTR and env regions were sequenced and
phylogenetic analyses were performed to characterize the new strains. Nucleotide
divergence and phylogeny results showed that four of the new strains belong to
the HTLV-Ib Central African subtype. The other two strains, one from the Efe
pygmy and one from Gabon, lie on distinct branches of the LTR and env trees with
respect to the four major HTLV-I subtypes. Despite the low bootstrap values,
likelihood mapping analyses proved that these strains can be considered two new
HTLV-I molecular subtypes, putatively named HTLV-Ie and HTLV-If. A relation
exists in the phylogenetic trees and in the likelihood maps between the new
subtypes and African STLV-I strains from Papio spp. and Cercopithecus spp.,
suggesting one or more interspecies transmission events in the past. This study
demonstrates that the phylogenetic subtyping of HTLV-I in the African continent
is far from being completed and that samples presenting an indeterminate serology
can potentially belong to new subtypes in humans. In addition, present day
serological tests do not reliably type strains within the HTLV-Ib Central African
subtype.
PMID- 9657947
TI - Proteolytic mapping of the coronavirus infectious bronchitis virus 1b
polyprotein: evidence for the presence of four cleavage sites of the 3C-like
proteinase and identification of two novel cleavage products.
AB - We have previously reported that the 3C-like proteinase of the coronavirus
infectious bronchitis virus (IBV) is responsible for processing of the 1a and
1a/1b polyproteins to three mature products of 24, 10, and 100 kDa (Liu et al.,
1994, 1997; Ng and Liu, 1998). The C-terminal cleavage site of the 100-kDa
protein was defined to be the Q891(1b)-S892(1b) dipeptide bond encoded by
nucleotides 15,129 to 15,134 (Liu and Brown, 1995). In this report, other
cleavage sites of the 3C-like proteinase in the polyprotein encoded by the ORF 1b
region were mapped by coexpression, deletion, and site-directed mutagenesis
studies. Using two ORF 1b-specific antisera, V58 and V17, three more Q-S(G)
dipeptide bonds, encoded by nucleotides 16,929 to 16,934, 18,492 to 18,497, and
19,506 to 19,511, respectively, were demonstrated to be the cleavage sites of the
3C-like proteinase. Cleavage at these four positions would result in the release
of four mature products with molecular masses of approximately 68, 58, 39, and 35
kDa. Among them, the 39- and 35-kDa proteins were specifically identified in IBV
infected cells. Taken together with the 100-kDa protein previously identified,
these results suggest that the ORF 1b region of IBV mRNA1 may be able to encode
five mature products.
PMID- 9657948
TI - Mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene
can confer altered drug sensitivities.
AB - Two herpes simplex virus mutants containing mutated residues within the conserved
Exo III motif of the polymerase gene were previously shown to be defective in 3'
5' exonuclease activity and exhibited extremely high mutation frequencies. In
this study, we have shown that these mutants also exhibited higher resistance to
phosphonoacetic acid and sensitivity to aphidicolin and all nucleoside analogs
tested, including acyclovir and gangciclovir, compared to wild-type virus. Marker
transfer experiments and sequencing analyses demonstrated that these altered
phenotypes were the result of mutations within the Exo III motif. The data
indicate that, aside from leading to exonuclease deficiency, mutations in the Exo
III motif may also affect interaction of nucleoside triphosphates with the
catalytic sites of polymerase activity.
PMID- 9657949
TI - Varicella-zoster virus ORF61 deletion mutants replicate in cell culture, but a
mutant with stop codons in ORF61 reverts to wild-type virus.
AB - Varicella-zoster virus (VZV) ORF61 encodes a phosphoprotein that transactivates
VZV promoters. Transfection of cells with cosmid DNAs, including a cosmid with a
large deletion in ORF61, resulted in a VZV ORF61 deletion mutant that was
impaired for growth in vitro and could be partially complemented by growth in
neuroblastoma or osteosarcoma cell lines. Cells infected with the VZV ORF61
deletion mutant expressed normal levels of an immediate-early VZV protein, but
had reduced levels of a late protein and showed abnormal syncytia. Carboxy
terminal truncation mutants of VZV ORF61 protein have a transrepressing phenotype
and inhibit the infectivity of cotransfected wild-type viral DNA. Transfection of
cells with cosmid DNAs, including a cosmid with stop codons that should result in
an ORF61 truncation mutant expressing a transrepressing protein that retains the
RING finger domain, resulted in a viral genome which reverted back to the wild
type sequence. BAL-31 exonuclease was used to produce deletions at the site of
the stop codons in ORF61 of the cosmid, resulting in loss of the RING finger
domain. Transfection of tissue culture cells with the ORF61 BAL-31 deletion
mutants and other cosmid DNAs yielded viable viruses. Thus, while deletion
mutants lacking the RING finger domain of ORF61 replicate in cell culture, a
mutant with stop codons that retains this domain could not be propagated and
reverted to wild-type virus.
PMID- 9657950
TI - Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus,
Jamaica.
AB - Although dengue (DEN) virus is the etiologic agent of dengue fever, the most
prevalent vector-borne viral disease in the world, precise information on the
antigenic structure of the dengue virion is limited. We have prepared a set of
murine monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of
DEN 2 virus and used these antibodies in a comprehensive biological and
biochemical analysis to identify 16 epitopes. Following domain nomenclature
developed for the related flavivirus, tick-borne encephalitis, three functional
domains were identified. Five epitopes associated with domain A were arranged in
three spatially independent regions. These A-domain epitopes were destroyed by
reduction, and antibodies reactive with these epitopes were able to block virus
hemagglutination, neutralize virus infectivity, and block virus-mediated cell
membrane fusion. Domain-A epitopes were present on the full-length E
glycoprotein, a 45-kDa tryptic peptide representing its first 400 amino acids
(aa) and a 22-kDa tryptic peptide representing at least aa 1-120. Four epitopes
mapped into domain B, as determined by their partial resistance to reduction and
the localization of these epitopes on a 9-kDa tryptic or chymotryptic peptide
fragment (aa 300-400). One domain-B-reactive MAb was also capable of binding to a
DEN 2 synthetic peptide corresponding to aa 333-351 of the E glycoprotein,
confirming the location of this domain. Domain-B epitopes elicited MAbs that were
potent neutralizers of virus infectivity and blocked hemagglutination, but they
did not block virus-mediated cell-membrane fusion. Domains A and B were spatially
associated. As with tick-borne encephalitis virus, determination of domain C was
more problematic; however, at least four epitopes had biochemical characteristics
consistent with C-domain epitopes.
PMID- 9657951
TI - Genes and regulatory sites of the "host-takeover module" in the terminal
redundancy of Bacillus subtilis bacteriophage SPO1.
AB - Early in infection of Bacillus subtilis by bacteriophage SPO1, the synthesis of
most host-specific macromolecules is replaced by the corresponding phage-specific
biosyntheses. It is believed that this subversion of the host biosynthetic
machinery is accomplished primarily by a cluster of early genes in the SPO1
terminal redundancy. Here we analyze the nucleotide sequence of this 11.5-kb
"host-takeover module," which appears to be designed for particularly efficient
expression. Promoters, ribosome-binding sites, and codon usage statistics all
show characteristics known to be associated with efficient function in B.
subtilis. The promoters and ribosome-binding sites have additional conserved
features which are not characteristic of their host counterparts and which may be
important for competition with host genes for the cellular biosynthetic
machinery. The module includes 24 genes, tightly packed into 12 operons driven by
the previously identified early promoters PE1 to PE12. The genes are smaller than
average, with half of them having fewer than 100 codons. Most of their inferred
products show little similarity to known proteins, although zinc finger, trans
membrane, and RNA polymerase-binding domains were identified. Transcription
termination and RNase III cleavage sites were found at appropriate locations.
PMID- 9657952
TI - The Maastricht strain and England strain of rat cytomegalovirus represent
different betaherpesvirus species rather than strains.
AB - The major immediate early (MIE) locus of the Maastricht strain of rat
cytomegalovirus (RCMV) was found to comprise five exons of which the first is
noncoding. The first three exons are spliced to either exon 4, generating IE1, or
exon 5, generating IE2. An additional splicing event unique to RCMV (Maastricht)
was identified in exon 5, resulting in a 466-bp deletion. IE1 transcripts were
detected exclusively during the IE phase of infection in vitro, whereas IE2
transcripts were detected during both the IE and late phase of infection. The
similarities between amino acid sequences derived from the MIE gene of RCMV
(Maastricht) and murine cytomegalovirus are low (22 and 37% for IE1 and IE2,
respectively). Surprisingly, the similarities between the MIE proteins of RCMV
(Maastricht) and the England strain of RCMV are also low (23 and 32% for IE1 and
IE2, respectively). This suggests that these RCMV strains represent different
betaherpesvirus species rather than strains. This is underscored by the
difference between both viruses in genome size as well as growth characteristics.
The existence of two different RCMV-like species might have important
implications for the use of these viruses as models for human cytomegalovirus.
PMID- 9657953
TI - Genome instability in BVDV: an examination of the sequence and structural
influences on RNA recombination.
AB - The cytopathogenic biotype of the pestivirus, bovine viral diarrhea virus, is
frequently a product of nonhomologous recombination in the region of the genome
encoding the viral NS2-NS3 proteins. The possibility that sequences or structures
in this region contributed to a hotspot for RNA recombination was examined. A PCR
based strategy was used to examine viral genomic RNA isolated from tissue samples
of cattle persistently infected with the noncytopathogenic biotype of the virus.
Analysis of two different regions of the viral genome revealed that recombination
was not restricted to particular sequences. Alignment of the genomic sequences
undergoing recombination and examination of the predicted secondary structures of
the participating RNAs revealed that the dissociation of partial, newly
synthesized negative strand RNAs from the positive strand template occurred at
many different sites on the molecule. Similarly, it appeared that the
reassociation of the RNA polymerase complex with a second positive strand
template was frequently influenced by short regions of homology between the
nascent RNA strand and open secondary structures in the template molecule.
PMID- 9657954
TI - Infectious bursal disease virus changes the potassium current properties of
chicken embryo fibroblasts.
AB - Infectious bursal disease virus (IBDV) is the causative agent of an economically
significant poultry disease. IBDV infection leads to apoptosis in chicken embryos
and cell cultures. Since changes in cellular ion fluxes during apoptosis have
been reported, we investigated the membrane ion currents of chicken embryo
fibroblasts (CEFs) inoculated with the Cu-1 strain of IBDV using the patch-clamp
recording technique. Incubation of CEFs with IBDV led to marked changes in their
K+ outward current properties, with respect to both the kinetics of activation
and inactivation and the Ca2+ dependence of the activation. The changes occurred
in a time-dependent manner and were complete after 8 h. UV-treated noninfectious
virions induced the same K+ current changes as live IBDV. When CEFs were
inoculated with IBDV after pretreatment with a neutralizing antibody, about 30%
of the cells showed a normal K+ current, whereas the rest exhibited K+ current
properties identical to or closely resembling those of IBDV-infected cells.
Incubation of CEFs with culture supernatant from IBDV-infected cells from which
the virus particles were removed had no influence on the K+ current. Our data
strongly suggest that the K+ current changes induced by IBDV are not due to virus
replication, but are the result of attachment and/or membrane penetration.
Possibly, the altered K+ current may delay the apoptotic process in CEFs after
IBDV infection.
PMID- 9657955
TI - Mechanisms of resistance of HIV-1 primary isolates to complement-mediated lysis.
AB - Previous studies suggested that HIV-1 primary isolates (PI) were resistant to
complement-mediated lysis (CML), while virus produced in certain T cell lines and
virus taken directly from the plasma of HIV+ persons were both susceptible to
CML. The purpose of this study was to investigate the mechanism(s) of PI
resistance. PI were resistant to CML using pooled seropositive serum as an
antibody source. Additionally, PI obtained from two patients at several times
over 2 years were resistant to CML using autologous antibody. PI were also
resistant to CML induced by monoclonal antibodies which neutralize a broad range
of PI. Resistance to CML was associated with low binding of antibody to PI but
was not due to low gp120 levels. Cell-line-derived virus and PI were equally
sensitive to CML induced by antibody to host-cell proteins, suggesting that PBMC
do not contribute properties to virions which make them more physically resistant
to CML in general but that PI resistance is restricted to CML induced by
antiviral antibody. These studies show that PI are resistant to CML mediated by
various antiviral antibodies and indicate that low binding of antibody to virus
is an important factor contributing to resistance.
PMID- 9657956
TI - A baculovirus mutant defective in PKIP, a protein which interacts with a virus
encoded protein kinase.
AB - We have found that a temperature-sensitive mutant of the baculovirus AcMNPV,
tsB97, is defective in PKIP, the product of ORF24 which was previously found to
interact with and stimulate the activity of a virus-encoded protein kinase, PK-1.
The mutant lacks the ability to form plaques and occlusion bodies at the
nonpermissive temperature. The mutant displays several properties which suggest a
defect in the latter half of the late phase of infection; these properties
include a delay in the shutoff of host protein synthesis, the presence of
aberrant electron-dense bodies associated with the virogenic stroma, and the
production of few, if any, progeny budded virus. A study of the expression of
selected late genes showed no difference in the timing or level of transcription
or translation of most late genes. However, elevated levels of the late 6.9K
protein, a protamine-like protein, were observed in mutant-infected cells at 24 h
postinfection, suggesting a defect in the regulation of this protein. Two
polypeptides, 40 and 6 kDa, exhibited considerably higher levels of steady-state
phosphorylation in wt-infected cells versus tsB97-infected cells at 24 h p.i. and
could be candidates for PK-1/PKIP-mediated phosphorylation. The tsB97 mutant also
displayed a severe defect in very late gene transcription which accounts for its
inability to form occlusion bodies. The effect of PKIP on very late gene
transcription may be a secondary effect of the block in the late phase of
infection. PKIP showed no ability to transactivate expression from a very late
promoter in transient expression assays.
PMID- 9657957
TI - Three closely related herpesviruses are associated with fibropapillomatosis in
marine turtles.
AB - Green turtle fibropapillomatosis is a neoplastic disease of increasingly
significant threat to the survivability of this species. Degenerate PCR primers
that target highly conserved regions of genes encoding herpesvirus DNA
polymerases were used to amplify a DNA sequence from fibropapillomas and fibromas
from Hawaiian and Florida green turtles. All of the tumors tested (n = 23) were
found to harbor viral DNA, whereas no viral DNA was detected in skin biopsies
from tumor-negative turtles. The tissue distribution of the green turtle
herpesvirus appears to be generally limited to tumors where viral DNA was found
to accumulate at approximately two to five copies per cell and is occasionally
detected, only by PCR, in some tissues normally associated with tumor
development. In addition, herpesviral DNA was detected in fibropapillomas from
two loggerhead and four olive ridley turtles. Nucleotide sequencing of a 483-bp
fragment of the turtle herpesvirus DNA polymerase gene determined that the
Florida green turtle and loggerhead turtle sequences are identical and differ
from the Hawaiian green turtle sequence by five nucleotide changes, which results
in two amino acid substitutions. The olive ridley sequence differs from the
Florida and Hawaiian green turtle sequences by 15 and 16 nucleotide changes,
respectively, resulting in four amino acid substitutions, three of which are
unique to the olive ridley sequence. Our data suggest that these closely related
turtle herpesviruses are intimately involved in the genesis of
fibropapillomatosis.
PMID- 9657958
TI - The acidic domain of pUL37x1 and gpUL37 plays a key role in transactivation of
HCMV DNA replication gene promoter constructions.
AB - Transient complementation of human cytomegalovirus (HCMV) oriLyt DNA replication
in permissive human diploid cells expressing replication genes under native
promoters requires its UL36-38 gene products. Two of the immediate early (IE)
proteins encoded by this locus, pUL37x1 and, to a lesser extent, gpUL37,
activated expression of HCMV early gene promoter constructions. The other IE
protein encoded by the UL36-38 locus, pUL36, and the early product, pUL38, did
not transactivate the HCMV early promoter constructions under similar conditions.
The acidic domain, common to both pUL37x1 and gpUL37, is required for activation
of HCMV early promoter constructions. Conversely, gpUL37 sequences downstream of
amino acid 199 are not required for transactivation of viral early promoters.
Taken together, these results suggest that the requirement for UL36-38 products
for HCMV DNA replication results, at least in part, from the requirement of the
transactivation of HCMV early DNA replication promoters by pUL37x1 and, to a
lesser extent, by gpUL37 and that the acidic domain is critical for this
activity.
PMID- 9657959
TI - Recombinant dengue virus type 1 NS3 protein exhibits specific viral RNA binding
and NTPase activity regulated by the NS5 protein.
AB - The full-length dengue virus NS3 protein has been successfully expressed as a 94
kDa GST fusion protein in Escherichia coli. Treatment of the purified fusion
protein with thrombin released a 68-kDa protein which is the expected molecular
mass for the DEN1 NS3 protein. The identity of this protein was confirmed by
Western blotting using dengue virus antisera. Two related activities of the
recombinant NS3 protein were characterized, which were the binding of the protein
to the 3'-noncoding region of the dengue virus RNA genome and NTPase activity. We
demonstrated using a band shift assay that the DEN1 NS3 protein could form a
complex with the stem-loop structure in the 3'-noncoding region (3'-NCR),
although sites outside the stem-loop may also participate in binding. Using
various unlabeled homopolymeric and heteropolymeric RNAs as competitors for
binding, it was further shown that the DEN1 NS3 protein exhibits preferential
binding to a 94-nt RNA transcript from the 3'-NCR of the dengue virus. The NTPase
activity of the recombinant DEN1 NS3 protein was characterized using a thin-layer
chromatography assay. We found that the DEN1 NS3 protein possesses some aspects
of NTPase activity, which are distinct from those found in other flaviviruses.
Although the NS3 protein was able to utilize all four ribonucleoside
triphosphates as its substrates, the NS3 protein showed a distinct preference for
purine triphosphates (i.e., ATP and GTP). The addition of poly(U) did not
stimulate NTPase activity in DEN1 NS3 protein, which contrasts with the reports
for other flaviviral NS3 proteins. However, NTPase activity was specifically
stimulated by the viral NS5 protein, which was manifested by a more than twofold
increase in the rate of ATP hydrolysis and a 25% increase in the yield of ADP at
the end of a 120-min reaction. These data suggest that the NTPase activity of the
NS3 protein may be regulated by the viral NS5 protein during virus replication.
PMID- 9657960
TI - Chaperonins.
AB - The molecular chaperones are a diverse set of protein families required for the
correct folding, transport and degradation of other proteins in vivo. There has
been great progress in understanding the structure and mechanism of action of the
chaperonin family, exemplified by Escherichia coli GroEL. The chaperonins are
large, double-ring oligomeric proteins that act as containers for the folding of
other protein subunits. Together with its co-protein GroES, GroEL binds non
native polypeptides and facilitates their refolding in an ATP-dependent manner.
The action of the ATPase cycle causes the substrate-binding surface of GroEL to
alternate in character between hydrophobic (binding/unfolding) and hydrophilic
(release/folding). ATP binding initiates a series of dramatic conformational
changes that bury the substrate-binding sites, lowering the affinity for non
native polypeptide. In the presence of ATP, GroES binds to GroEL, forming a large
chamber that encapsulates substrate proteins for folding. For proteins whose
folding is absolutely dependent on the full GroE system, ATP binding (but not
hydrolysis) in the encapsulating ring is needed to initiate protein folding.
Similarly, ATP binding, but not hydrolysis, in the opposite GroEL ring is needed
to release GroES, thus opening the chamber. If the released substrate protein is
still not correctly folded, it will go through another round of interaction with
GroEL.
PMID- 9657961
TI - A 211-bp enhancer of the rat uncoupling protein-1 (UCP-1) gene controls specific
and regulated expression in brown adipose tissue.
AB - The uncoupling protein-1 gene is uniquely expressed in brown adipose tissue (BAT)
and is positively regulated by cold exposure of animals and the sympathetic
nervous system. To analyse the importance of a previously identified 211-bp
enhancer [Cassard-Doulcier, Gelly, Fox, Schrementi, Raimbault, Klaus, Forest,
Bouillaud and Ricquier (1993) Mol. Endocrinol. 7, 497-506] in the tissue-specific
expression of this gene, transgenic mice were generated using the chloramphenicol
acetyltransferase (CAT) gene as a reporter gene. One out of fourteen lines of the
control transgenic mice bearing the Herpes simplex thymidine kinase (TK) promoter
expressed weakly the CAT reporter gene in several tissues, whereas the other
lines did not express CAT. Eight founders bearing the 211-bp enhancer-TK
transgene were obtained. In six lines, no expression of CAT was detected. In one
line, the expression of CAT was restricted to BAT. In another line, the
expression of CAT was found in BAT and, to a lesser extent, in testis. Moreover,
in these lines a marked and specific increase in the expression of the reporter
gene in BAT was observed either after exposure of mice to the cold or by treating
them with a beta-adrenoceptor agonist drug. These results demonstrate that the
211-bp enhancer alone is sufficient to both direct and restrict expression to
BAT. This enhancer also mediates the transcriptional response of the gene to beta
adrenergic stimulation, although it does not contain conserved cAMP response
element.
PMID- 9657962
TI - Identification of a human homologue of the vesicle-associated membrane protein
(VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that
binds to VAMP.
AB - We report the identification of a human homologue of the vesicle-associated
membrane protein (VAMP)-associated protein (hVAP-33) that has been implicated in
neuronal exocytosis in Aplysia californica. This hVAP-33 shared 50% amino acid
identity with the A. californica form and had similar length, structural
organization and VAMP-binding abilities. However, in contrast with the neuron
specific expression seen in A. californica, hVAP-33 was broadly expressed,
suggesting possible roles in vesicle fusion in both neuronal and non-neuronal
cells.
PMID- 9657963
TI - Loss of the hepatic glycogen-binding subunit (GL) of protein phosphatase 1
underlies deficient glycogen synthesis in insulin-dependent diabetic rats and in
adrenalectomized starved rats.
AB - Hepatic glycogen synthesis is impaired in insulin-dependent diabetic rats and in
adrenalectomized starved rats, and although this is known to be due to defective
activation of glycogen synthase by glycogen synthase phosphatase, the underlying
molecular mechanism has not been delineated. Glycogen synthase phosphatase
comprises the catalytic subunit of protein phosphatase 1 (PP1) complexed with the
hepatic glycogen-binding subunit, termed GL. In liver extracts of insulin
dependent diabetic and adrenalectomized starved rats, the level of GL was shown
by immunoblotting to be substantially reduced compared with that in control
extracts, whereas the level of PP1 catalytic subunit was not affected by these
treatments. Insulin administration to diabetic rats restored the level of GL and
prolonged administration raised it above the control levels, whereas re-feeding
partially restored the GL level in adrenalectomized starved rats. The regulation
of GL protein levels by insulin and starvation/feeding was shown to correlate
with changes in the level of the GL mRNA, indicating that the long-term
regulation of the hepatic glycogen-associated form of PP1 by insulin, and hence
the activity of hepatic glycogen synthase, is predominantly mediated through
changes in the level of the GL mRNA.
PMID- 9657964
TI - DNA triple-helix formation on nucleosome-bound poly(dA).poly(dT) tracts.
AB - We have used DNase I and hydroxyl-radical footprinting to examine the formation
of intermolecular DNA triple helices on nucleosome-bound DNA fragments containing
An.Tn tracts. We found that it is possible to form triplexes on these nucleosome
bound DNAs, but the stability of the complexes depends on the orientation of the
A tract with respect to the protein surface. Hydroxyl-radical cleavage of these
complexes suggests that the DNA fragments are still associated with the
nucleosome. However, the phased cleavage pattern is lost in the vicinity of the
triplex, suggesting that the DNA has locally moved away from the protein surface.
PMID- 9657965
TI - Interplay between cytoplasmic Ca2+ and the ATP/ADP ratio: a feedback control
mechanism in mouse pancreatic islets.
AB - In pancreatic beta cells, the increase in the ATP/ADP ratio that follows a
stimulation by glucose is thought to play an important role in the Ca2+-dependent
increase in insulin secretion. Here we have investigated the possible
interactions between Ca2+ and adenine nucleotides in mouse islets. Measurements
of both parameters in the same single islet showed that the rise in the ATP/ADP
ratio precedes any rise in the cytoplasmic free-Ca2+ concentration ([Ca2+]i) and
is already present during the initial transient lowering of [Ca2+]i produced by
the sugar. Blockade of Ca2+ influx with nimodipine did not prevent the
concentration-dependent increase in the ATP/ADP ratio produced by glucose and
even augmented the ratio at all glucose concentrations which normally stimulate
Ca2+ influx. In contrast, stimulation of Ca2+ influx by 30 mM K+ or 100 microM
tolbutamide lowered the ATP/ADP ratio. This lowering was of rapid onset and
reversibility, sustained and prevented by nimodipine or omission of extracellular
Ca2+. It was, however, not attenuated after blockade of secretion by activation
of alpha2-adrenoceptors. The difference in islet ATP/ADP ratio during blockade
and stimulation of Ca2+ influx was similar to that observed between threshold and
submaximal glucose concentrations. The results suggest that the following
feedback loop could control the oscillations of membrane potential and [Ca2+]i in
beta cells. Glucose metabolism increases the ATP/ADP ratio in a Ca2+-independent
manner, which leads to closure of ATP-sensitive K+ channels, depolarization and
stimulation of Ca2+ influx. The resulting increase in [Ca2+]i causes a larger
consumption than production of ATP, which induces reopening of ATP-sensitive K+
channels and arrest of Ca2+ influx. Upon lowering of [Ca2+]i the ATP/ADP ratio
increases again and a new cycle may start.
PMID- 9657966
TI - Insight into naphthoquinone metabolism: beta-glucosidase-catalysed hydrolysis of
hydrojuglone beta-D-glucopyranoside.
AB - In plants, the naphthoquinone juglone is known to be involved in pathogenic
defence mechanisms, but it may also take part in plant developmental processes.
This naphthoquinone can accumulate in a glycosylated form, namely hydrojuglone
beta-d-glucopyranoside. The structural configuration of this compound was shown
to be 1, 5-dihydroxy-4-naphthalenyl-beta-d-glucopyranoside by means of MS, NMR
and nuclear Overhauser effect spectroscopy analyses. A hydrojuglone beta-d
glucopyranoside beta-glucosidase (EC 3.2.1.21) was purified to homogeneity from
Juglans regia L. The enzyme catalysed the release of juglone from hydrojuglone
beta-d-glucopyranoside with high specificity and showed Michaelis-Menten kinetics
with Km=0.62 mM and Vmax=14.5 microkat/mg of protein. This enzyme also showed a
higher activity towards beta-d-fucosyl than beta-d-glucosyl bonds. The purified
enzyme had an apparent Mr of 64000 by SDS/PAGE and a pI 8.9 by isoelectrofocusing
PAGE. The purified enzyme was inhibited by several bivalent cations, such as
Cu2+, Fe2+, Hg2+, and by d-glucono-1,5-lactone, showing non-competitive
inhibition of the mixed type.
PMID- 9657967
TI - Identification and purification of the reconstitutively active glutamine carrier
from rat kidney mitochondria.
AB - The glutamine carrier from rat kidney mitochondria, solubilized in dodecyl
octaoxyethylene ether (C12E8) and partly purified on hydroxyapatite, was
identified and completely purified by Celite chromatography. On SDS/PAGE, the
purified glutamine carrier consisted of a single protein band with an apparent
molecular mass of 41.5 kDa. When reconstituted into liposomes, the glutamine
carrier catalysed both the unidirectional flux of glutamine and the
glutamine/glutamine countertransport, which were completely inhibitable by a
mixture of pyridoxal 5'-phosphate and N-ethylmaleimide. The carrier protein was
purified 474-fold with a recovery of 58% and a protein yield of 0.12% with
respect to the mitochondrial extract. The glutamine carrier-mediated transport is
quite specific for l-glutamine. l-Asparagine is the only other amino acid that is
efficiently transported by the reconstituted carrier protein. d-Glutamine, l
glutamate and l-aspartate are very poor substrates. The transport activity was
inhibited by several thiol-group and amino-group reagents.
PMID- 9657968
TI - The cellular response to oxidative stress: influences of mitogen-activated
protein kinase signalling pathways on cell survival.
AB - The mammalian response to stress is complex, often involving multiple signalling
pathways that act in concert to influence cell fate. To examine potential
interactions between the signalling cascades, we have focused on the effects of a
model oxidant stress in a single cell type through an examination of the relative
influences of mitogen-activated protein kinases (MAPKs) as well as two proposed
apoptosis regulators, nuclear factor kappaB (NF-kappaB) and Bcl-2, in determining
cell survival. Treatment of HeLa cells with H2O2 resulted in a time- and dose
dependent induction of apoptosis accompanied by sustained activation of all three
MAPK subfamilies: extracellular signal-regulated protein kinase (ERK), c-Jun N
terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. This H2O2
induced apoptosis was markedly enhanced when ERK2 activation was selectively
inhibited by PD098059. Apoptosis decreased when JNK/SAPK activation was inhibited
by expression of a dominant negative mutant form of SAPK/ERK kinase 1. Inhibition
of the p38 kinase activity with p38-specific inhibitors SB202190 and SB203580 had
no effect on cell survival. Because NF-kappaB activation by H2O2 is potentially
related to both the ERK and JNK/SAPK signalling pathways, we examined the effects
of inhibiting the activation of NF-kappaB; this interference had no effect on the
cellular response to H2O2. Overexpression of the anti-apoptotic protein Bcl-2
significantly decreased the apoptosis seen after treatment with H2O2 without
altering ERK or JNK/SAPK activities. Our results suggest that ERK and JNK/SAPK
act in opposition to influence cell survival in response to oxidative stress,
whereas neither p38 nor NF-kappaB affects the outcome. Bcl-2 acts independently
and downstream of ERK and JNK/SAPK to enhance the survival of H2O2-treated cells.
PMID- 9657969
TI - Acute desensitization of phospholipase C-coupled muscarinic M3 receptors but not
gonadotropin-releasing hormone receptors co-expressed in alphaT3-1 cells:
implications for mechanisms of rapid desensitization.
AB - In the present study we have expressed the muscarinic M3 receptor in an
immortalized mouse pituitary cell line (alphaT3-1), which expresses an endogenous
gonadotropin-releasing hormone (GnRH) receptor, to examine potential differences
in acute receptor regulation. Both of these receptors couple to the activation of
phosphoinositide-specific phospholipase C (PLC) in these cells and we demonstrate
that, despite expression in the same cell background, acute desensitization is a
feature of muscarinic M3 receptors but not of GnRH receptors. We show that, when
the concentrations of GnRH and methacholine are matched to give approximately
equivalent maximal elevations of Ins(1,4,5)P3, the GnRH receptor is able to
sustain PLC activity at the initial rate, whereas the muscarinic M3 receptor
cannot. Thus PLC-activating G-protein-coupled receptors are able to undergo rapid
desensitization in this cell line, indicating that the desensitization profile is
receptor-specific rather than cell-specific. This argues strongly that post
receptor regulatory features do not have a prominent role in mediating rapid
desensitization in these cells. Furthermore GnRH receptor-mediated PLC activity
is sustained despite a marked and persistent depletion in the steady-state level
of PtdIns(4,5)P2. In contrast, activation of muscarinic receptors is not
sustained despite only a transient decrease in PtdIns(4,5)P2 concentration. Thus,
whereas the contribution of PtdIns(4,5)P2 depletion to the temporal profile of
receptor-mediated PLC signalling has been difficult to assess, the present
results demonstrate that this is unlikely to be of importance in these cells. We
suggest that unique structural features of the GnRH receptor result in a lack of
appropriate regulatory phospho-acceptor sites and that the absence of agonist
dependent phosphorylation might underlie the lack of acute regulation.
PMID- 9657970
TI - Developmental effect of polyamine depletion in Caenorhabditis elegans.
AB - Ornithine decarboxylase (ODC) catalyses the conversion of ornithine to
putrescine, an obligate precursor to the polyamines spermidine and spermine. We
reported previously that homozygous odc-1 (pc13) worms have no detectable ODC
activity. Despite their inability to make polyamines, these mutant worms appear
normal, but with a slight reduction in total brood size, when grown in complex
medium that presumably contains polyamines. We now show that when ODC-deficient
worms are transferred to polyamine-free medium, they show a strong phenotype. odc
1 worms have two different fates, depending upon the developmental stage at which
polyamines are removed. If the polyamines are removed at the L1 larval stage, the
mutant animals develop into adult hermaphrodites that produce very few or no
eggs. In contrast, if mutant larvae at the later L4 stage of development are
transferred to polyamine-deficient medium, they develop and lay eggs normally.
However, approx. 90% of the eggs yield embryos that, although well
differentiated, arrest at early stage 3. Either maternal or zygotic expression of
ODC provides partial rescue of embryonic lethality. Supplementing deficient
medium with the polyamine spermidine allows ODC-deficient worms to develop as on
complex medium. Together, these findings suggest that ODC activity is most
critically required during oogenesis and embryogenesis and, furthermore, that
exogenous polyamines can override the requirement for ODC activity.
PMID- 9657971
TI - Sequence, catalytic properties and expression of chicken glutathione-dependent
prostaglandin D2 synthase, a novel class Sigma glutathione S-transferase.
AB - The Expressed Sequence Tag database has been screened for cDNA clones encoding
prostaglandin D2 synthases (PGDSs) by using a BLAST search with the N-terminal
amino acid sequence of rat GSH-dependent PGDS, a class Sigma glutathione S
transferase (GST). This resulted in the identification of a cDNA from chicken
spleen containing an insert of approx. 950 bp that encodes a protein of 199 amino
acid residues with a predicted molecular mass of 22732 Da. The deduced primary
structure of the chicken protein was not only found to possess 70% sequence
identity with rat PGDS but it also demonstrated more than 35% identity with class
Sigma GSTs from a range of invertebrates. The open reading frame of the chicken
cDNA was expressed in Escherichia coli and the purified protein was found to
display high PGDS activity. It also catalysed the conjugation of glutathione with
a wide range of aryl halides, organic isothiocyanates and alpha,beta-unsaturated
carbonyls, and exhibited glutathione peroxidase activity towards cumene
hydroperoxide. Like other GSTs, chicken PGDS was found to be inhibited by non
substrate ligands such as Cibacron Blue, haematin and organotin compounds.
Western blotting experiments showed that among the organs studied, the expression
of PGDS in the female chicken is highest in liver, kidney and intestine, with
only small amounts of the enzyme being found in chicken spleen; in contrast, the
rat has highest levels of PGDS in the spleen. Collectively, these results show
that the structure and function, but not the expression, of the GSH-requiring
PGDS is conserved between chicken and rat.
PMID- 9657972
TI - Chemical mechanism of the endogenous argininosuccinate lyase activity of duck
lens delta2-crystallin.
AB - The endogenous argininosuccinate lyase activity of duck delta2-crystallin was
specifically inactivated by the histidine-specific reagent, diethyl
pyrocarbonate. The protein was protected by l-citrulline or l-arginine from the
diethyl pyrocarbonate inactivation. To characterize further the chemical
mechanism of the delta2-crystallin-catalysed reaction, deuterium-labelled
argininosuccinate was enzymically synthesized from fumarate and l-arginine with
delta2-crystallin in 2H2O. The argininosuccinate synthesized contained about 19%
of the anhydride form; however, the deuterium was clearly demonstrated to be
incorporated enantioselectively. Only the pro-HR atom at C-9 of the succinate
moiety was labelled in the [2H]argininosuccinate-9-d synthesized, which indicates
an anti-elimination mechanism for the endogenous argininosuccinate lyase activity
of delta2-crystallin. The enzymic activity of duck lens delta2-crystallin in the
pH range 5.5-8.5 was investigated using both protium- and deuterium-labelled
argininosuccinate as the substrate. From the logkcat versus pH plot, two
molecular pKa values of 6.18+/-0.02 and 8.75+/-0.03 were detected in the delta2
crystallin-argininosuccinate binary complex. The former must be dehydronated and
the latter hydronated to achieve an optimum reaction rate. The logkcat/Km versus
pH plot suggested two molecular pKa values of 5.96+/-0.09 and 8.29+/-0.10 for the
free delta2-crystallin to be involved in the substrate binding. Small kinetic
isotope effects of 1.17+/-0.02 and 1.05+/-0.09 were found for kcat and kcat/Km
respectively. Combining results from labelling and kinetic analysis indicates
that the endogenous argininosuccinate lyase activity of duck delta2-crystallin is
compatible with a stepwise E1cB mechanism, the rate-limiting step probably at the
C-N bond-cleavage step.
PMID- 9657973
TI - Intestinal absorption of bile acids: paradoxical behaviour of the 14 kDa ileal
lipid-binding protein in differential photoaffinity labelling.
AB - Photoaffinity labelling of brush border membrane vesicles from rabbit ileum with
radiolabelled 3,3-azo and 7,7-azo derivatives of taurocholate identified integral
membrane proteins of molecular masses 93 and 46 kDa, as well as a 14 kDa
peripheral membrane protein, as components of the ileal Na+/bile acid transport
system [Kramer, Girbig, Gutjahr, Kowalewski, Jouvenal, Muller, Tripier and Wess
(1993) J. Biol. Chem. 268, 18035-18046]. Differential photoaffinity labelling in
the presence of non-radiolabelled bile acid derivatives led, as expected, to a
concentration-dependent decrease in the extent of labelling of the 93 and 46 kDa
transmembrane proteins, which are the monomeric and dimeric forms of the ileal
bile acid transporter protein. The extent of labelling of the 14 kDa ileal lipid
binding protein (ILBP), however, increased on the addition of unlabelled bile
acids, the increase being dependent on the structure of the bile acid added. The
possibility of artifacts was excluded by photoaffinity labelling experiments in
the frozen state as well as by model calculations. The experimental results
suggest that the binding of bile acids to ILBP can increase the affinity of ILBP
for bile acids. These results would be in accordance with a substrate-load
modification of transport activity and a positive-feedback regulation mechanism
for active uptake of bile acid in the ileum.
PMID- 9657974
TI - Induction of stress-activated protein kinases/c-Jun N-terminal kinases by the p55
tumour necrosis factor receptor does not require sphingomyelinases.
AB - Ceramide has been implicated in the activation of stress-activated protein
kinases/c-Jun N-terminal kinases (SAPK/JNK). Binding of tumour necrosis factor
(TNF) to its 55 kDa receptor (TR55) leads to the generation of ceramide through
activation of either acid or neutral sphingomyelinase (A/N-SMase) as well as to
potent activation of SAPK/JNK. We have examined a putative role of both N- and A
SMase in the TR55-dependent activation of SAPK/JNK. The analysis of TR55 deletion
mutants expressed in 70Z/3 pre-B cells revealed that activation of SAPK/JNK
occurs independently of N-SMase. Although both SAPK/JNK and A-SMase are activated
by the death domain of TR55, pharmacological prevention of the TR55-dependent
activation of A-SMase, or proteolytic degradation of A-SMase in 70Z/3 cells, did
not impair SAPK/JNK activation, indicating that SAPK/JNK are not secondary to A
SMase. In addition, proteolytic degradation of A-SMase also did not affect
SAPK/JNK activation by ultraviolet (UV-C) irradiation, arguing against a general
role of A-SMase in stress-mediated responses. Furthermore, fibroblasts from
Niemann-Pick A patients deficient in A-SMase did not show altered activation of
SAPK/JNK in response to either TNF or UV-C. These results suggest that TR55 can
activate SAPK/JNK without direct participation of sphingomyelinases or ceramide.
PMID- 9657975
TI - Multidrug resistance transporter P-glycoprotein has distinct but interacting
binding sites for cytotoxic drugs and reversing agents.
AB - P-Glycoprotein, the plasma membrane protein responsible for the multidrug
resistance of some tumour cells, is an active transporter of a number of
structurally unrelated hydrophobic drugs. We have characterized the modulation of
its ATPase activity by a multidrug-resistance-related cytotoxic drug,
vinblastine, and different multidrug-resistance-reversing agents, verapamil and
the dihydropyridines nicardipine, nimodipine, nitrendipine, nifedipine and
azidopine. P-Glycoprotein ATPase activity was measured by using native membrane
vesicles containing large amounts of P-glycoprotein, prepared from the highly
multidrug-resistant lung fibroblasts DC-3F/ADX. P-Glycoprotein ATPase is
activated by verapamil and by nicardipine but not by vinblastine. Among the five
dihydropyridines tested, the higher the hydrophobicity, the higher was the
activation factor with respect to the basal activity and the lower was the half
maximal activating concentration. The vinblastine-specific binding on P
glycoprotein is reported by the inhibitions of the verapamil- and the nicardipine
stimulated ATPase. These inhibitions are purely competitive, which means that the
bindings of vinblastine and verapamil, or vinblastine and nicardipine, on P
glycoprotein are mutually exclusive. In contrast, verapamil and nicardipine
display mutually non-competitive interactions. This demonstrates the existence of
two distinct specific sites for these two P-glycoprotein modulators on which they
can bind simultaneously and separately to the vinblastine site. The nicardipine
stimulated ATPase activity in the presence of the other dihydropyridines shows
mixed-type inhibitions. These dihydropyridines have thus different binding sites
that interact mutually to decrease their respective, separately determined
affinities. This could be due to steric constraints between sites close to each
other. This is supported by the observation that vinblastine binding is not
mutually exclusive with nifedipine or nitrendipine binding, whereas it is
mutually exclusive with nicardipine. Moreover, verapamil binding also interacts
with the five dihydropyridines by mixed inhibitions, with different
destabilization factors. On the whole our enzymic data show that P-glycoprotein
has distinct but interacting binding sites for various modulators of its ATPase
function.
PMID- 9657976
TI - Human mitochondrial phosphoenolpyruvate carboxykinase 2 gene. Structure,
chromosomal localization and tissue-specific expression.
AB - The mitochodrial (mt) phosphoenolpyruvate carboxykinase 2 (PCK2) gene was
isolated by screening a human genomic library with a rat cytosolic (cy) PCK1 cDNA
probe comprising sequences from exons 2-9 and by PCR amplification of human
genomic DNA spanning consecutive exons with known primer pairs from mtPCK2 cDNA
containing sequences from two putative neighbouring exons. The mtPCK2 gene spans
approx. 10 kb and consists of ten exons and nine introns. All exon-intron
junction sequences match the classical GT/AG rule. Northern blot analysis of
poly(A)+ and total RNA from various tissues revealed one mRNA species of approx.
2.4 kb. The gene is expressed in a variety of human tissues, mainly in liver,
kidney, pancreas, intestine and fibroblasts. In contrast with the cytosolic
isoenzyme, the mitochondrial form might not have a purely gluconeogenic function.
The mtPCK2 gene maps to chromosome 14q11.2-q12, in contrast with the cyPCK1 gene
located on 20q13.2-q13.31.
PMID- 9657977
TI - Critical role of arg433 in rat transketolase activity as probed by site-directed
mutagenesis.
AB - It has been shown that one arginine per monomer at an unknown position is
essential for enzyme activity of the homodimeric transketolase (TK) [Kremer, Egan
and Sable (1980) J. Biol. Chem. 255, 2405-2410]. To identify the critical
arginine, four highly conserved arginine residues of rat TK (Arg102, Arg350,
Arg433 and Arg506) were replaced with alanine by site-directed mutagenesis. Wild
type and mutant TK proteins were produced in Escherichia coli and characterized.
The Arg102-->Ala mutant exhibited similar catalytic activity to the wild-type
enzyme, whereas Arg350-->Ala, Arg506-->Ala and Arg433-->Ala mutants exhibited
36.7, 37.0 and 6.1% of the wild-type activity respectively. Three recombinant
proteins (wild-type, Arg350-->Ala and Arg433-->Ala) were purified to apparent
homogeneity using Ni2+-affinity chromatography and further characterized. All
these proteins were able to form homodimers (148 kDa), as shown by immunoblot
analysis subsequent to non-denaturing gel electrophoresis. The Arg433-->Ala
mutant protein was less stable than the wild-type and Arg350-->Ala proteins at 55
degrees C. Kinetic analyses revealed that both Vmax and Km values were markedly
affected in the Arg433-->Ala mutant. The Km values for two substrates xylulose 5
phosphate and ribose 5-phosphate were 11.5- and 24.3-fold higher respectively.
The kcat/Km values of the Arg433-->Ala mutant for the two substrates were less
than 1% of those of the wild-type protein. Molecular modelling of the rat TK
revealed that Arg433 of one monomer has three potential hydrogen-bond
interactions with the catalytically important highly conserved loop of the other
monomer. Thus, our biochemical analyses and modelling data suggest the critical
role of the previously uncharacterized Arg433 in TK activity.
PMID- 9657978
TI - Active Lyn protein tyrosine kinase is selectively enriched within membrane
microdomains of resting platelets.
AB - Circulating platelets are primed to respond very rapidly to thrombogenic stimuli,
but most platelets complete their lifespan without ever becoming activated.
Platelet activation is accompanied by waves of sequential tyrosine
phosphorylation thought to involve members of the Src family of protein tyrosine
kinases (PTKs). We show here that resting platelets contain highly active
pp53/56(Lyn) PTK within membrane microdomains (rafts) isolated biochemically with
or without the use of detergent. This fraction is also greatly enriched in the
transmembrane glycoprotein CD36, known to associate with Lyn PTK, but in
transfection studies we could find no evidence to suggest that CD36 affects the
distribution or function of Lyn. Upon platelet activation Lyn activity remains
constant or diminishes and pp60(c-src) PTK within this fraction becomes highly
activated, indicating the dynamic nature of the membrane microdomains. It is
suggested that the function of active Lyn PTK in the resting platelet is to allow
prolonged survival of this anucleate cell.
PMID- 9657979
TI - Distribution of the mevalonate and glyceraldehyde phosphate/pyruvate pathways for
isoprenoid biosynthesis in unicellular algae and the cyanobacterium Synechocystis
PCC 6714.
AB - Isopentenyl diphosphate, the universal isoprenoid precursor, can be produced by
two different biosynthetic routes: either via the acetate/mevalonate (MVA)
pathway, or via the more recently identified MVA-independent glyceraldehyde
phosphate/pyruvate pathway. These two pathways are easily differentiated by
incorporation of [1-13C]glucose and analysis of the resulting labelling patterns
found in the isoprenoids. This method was successfully applied to several
unicellular algae raised under heterotrophic growth conditions and allowed for
the identification of the pathways that were utilized for isoprenoid
biosynthesis. All isoprenoids examined (sterols, phytol, carotenoids) of the
green algae Chlorella fusca and Chlamydomonas reinhardtii were synthesized via
the GAP/pyruvate pathway, as in another previously investigated green alga,
Scenedesmus obliquus, which was also shown in this study to synthesize ubiquinone
by the same MVA-independent route. In the red alga Cyanidium caldarium and in the
Chrysophyte Ochromonas danica a clear dichotomy was observed: as in higher
plants, sterols were formed via the MVA route, whereas chloroplast isoprenoids
(phytol in Cy. caldarium and O. danica and beta-carotene in O. danica) were
synthesized via the GAP/pyruvate route. In contrast, the Euglenophyte Euglena
gracilis synthesized ergosterol, as well as phytol, via the acetate/MVA route.
Similar feeding experiments were performed with the cyanobacterium Synechocystis
PCC 6714 using [1-13C]- and [6-13C]-glucose. The two isoprenoids examined, phytol
and beta-carotene, were shown to have the typical labelling pattern derived from
the GAP/pyruvate route.
PMID- 9657980
TI - Cloning of subunits of convulxin, a collagen-like platelet-aggregating protein
from Crotalus durissus terrificus venom.
AB - Convulxin (CVX) is a potent platelet-aggregating glycoprotein from the venom of
the snake Crotalus durissus terrificus. It consists of two subunits, alpha and
beta, joined by disulphide bridges in a hexameric structure. A cDNA library from
venom gland was constructed in the vector pT3T7. The cloned cDNAs encoding the
two chains of CVX were sequenced. Both are preceded by an identical 23-amino acid
peptide signal sequence and encode sequences of 135 amino acids for the alpha
chain and 125 amino acids for the beta chain. These polypeptides include a
carbohydrate-recognition domain (CRD) in which some of the specific amino acids
required for binding Ca2+ and galactose or mannose are absent. The presence of
such a domain means that CVX can be included in the family of C-type lectins
along with other snake venom proteins, although it is not a true lectin. Assuming
that the localization of intracatenary disulphide bridges of each CVX chain is
similar to that of the CRD and that an intercatenary bridge between the alpha and
beta chains is similar to that of the C-type lectin botrocetin, we postulate the
existence of an additional intercatenary bridge, which explains the tridimeric
structure (alphabeta)3 of CVX.
PMID- 9657981
TI - Refolding of urea-denatured adenylate kinase.
AB - The refolding of urea-denatured adenylate kinase (EC 2.7.4.3) has been followed
by formation of the secondary structure, change of surface hydrophobicity and
recovery of catalytic activity. During refolding of adenylate kinase with a 20-80
fold dilution of 4 M urea-denatured enzyme at 10 degrees C, the formation of the
secondary structure is a fast process with a rate constant of >0.16 s-1.
Transient enhancement of the 8-anilino-1-naphthalenesulphonate (ANS) fluorescence
intensity is followed by a fluorescence decrease to the level equal to the value
characteristic of native enzyme. The desorption of ANS binding fluorescence is
relatively slow and can be fitted to a first order reaction with a rate constant
of 0.004 s-1 when the ANS is present in the dilution buffer. The desorption of
ANS-binding fluorescence is accelerated in the presence of nucleotide substrates.
The rate constants are increased to 0.049, 0. 029, 0.028 and 0.029 s-1 in the
presence of 1 mM AMP, MgATP, ATP and ADP respectively. The refolding rate
constant calculated from the initial fluorescence intensity after mixing ANS with
protein at different refolding intervals is 0.016 s-1, which is faster than those
obtained when ANS is present throughout the refolding process, indicating that
the binding of ANS with a partially folded intermediate retards its further
refolding to its native structure. The reactivation rate is even faster than the
rates of refolding monitored in the absence of substrates, showing that the
refolding is accelerated in the presence of the substrates. A possible refolding
pathway and the accelerating effect of substrates are discussed.
PMID- 9657982
TI - Protection from oxidative inactivation of the 20S proteasome by heat-shock
protein 90.
AB - Heat-shock protein 90 (Hsp 90) has been implicated in both protection against
oxidative inactivation and inhibition of the multicatalytic proteinase (MCP, also
known as 20 S proteasome). We report here that the protective and inhibitory
effects of Hsp 90 depend on the activation state of the proteasome. Hsp 90 (and
also alpha-crystallin) inhibits the N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activity
(Cbz=benzyloxycarbonyl; MCA=7-amido-4-methylcoumarin) when the rat liver MCP is
in its latent form, but no inhibitory effects are observed when the MCP is in its
active form. Metal-catalysed oxidation of the active MCP inactivates the Ala-Ala
Phe-MCA-hydrolysing (chymotrypsin-like), N-Boc-Leu-Ser-Thr-Arg-MCA-hydrolysing
(trypsin-like; Boc=t-butyloxycarbonyl), N-Cbz-Leu-Leu-Glu-beta-naphthylamine
hydrolysing (peptidylglutamyl-peptide hydrolase) and N-Cbz-Leu-Leu-Leu-MCA
hydrolysing activities, whereas these activities are actually increased when the
MCP is in its latent form. Hsp 90 protects against oxidative inactivation of the
trypsin-like and N-Cbz-Leu-Leu-Leu-MCA-hydrolysing activities of the MCP active
form, and alpha-crystallin protects the trypsin-like activity. The specificity of
the Hsp 90-mediated protection was assessed by a quantitative analysis of the two
dimensional electrophoretic pattern of MCP subunits before and after oxidation of
the MCP, in the presence or absence of Hsp 90. Treatment of the FAO hepatoma cell
line with iron and ascorbate was found to inactivate the MCP. Hsp 90
overexpression obtained by challenging the cells with iron was associated with a
decreased susceptibility to oxidative inactivation of the MCP trypsin-like
activity. Depletion of Hsp 90 by using antisense oligonucleotides resulted in an
increased susceptibility to oxidative inactivation of the MCP trypsin-like
activity, providing evidence for the physiological relevance of Hsp 90-mediated
protection of the MCP.
PMID- 9657983
TI - Cloning of the gene and cDNA for hamster chymase 2, and expression of chymase 1,
chymase 2 and angiotensin-converting enzyme in the terminal stage of
cardiomyopathic hearts.
AB - Chymase is responsible for the formation of angiotensin II, which plays crucial
roles in the pathogenesis of cardiovascular diseases. In the present study we
determined the gene organization of a novel hamster chymase (hamster chymase 2)
and analysed the expression of chymase 1, chymase 2 and angiotensin-converting
enzyme (ACE) in hamster hearts at the terminal stage of cardiomyopathy. The gene
encoding hamster chymase 2 is 3.2 kb in length and has five exons and four
intervening sequences. The overall organization of this gene is similar to that
of several other serine proteases. The deduced amino acid sequence revealed the
existence of a preproenzyme composed of a signal peptide with 19 amino acids, a
propeptide with two amino acids and a catalytic domain with 226 amino acids. The
predicted full sequence of the catalytic domain was revealed to be very similar
to the sequences of mouse mast-cell protease 5 (86%), rat mast-cell protease III
(85%) and human chymase (70%) and less similar to hamster chymase 1 (56%). The
expression of chymase 1 in heart was higher than that of chymase 2. The cardiac
chymase-like activity, as well as the mRNA levels of chymase 1 and 2 of BIO 14.6
cardiomyopathic hamsters at the age of 60 weeks were increased 3.4-, 2.8- and 5.1
fold respectively compared with age-matched BIO F1B control hamsters. The cardiac
ACE activity and the ACE mRNA level of cardiomyopathic hamsters were also
increased 4.1- and 2.4-fold compared with those of age-matched controls. These
results suggest that up-regulation of both ACE and chymases participates in the
pathophysiology of the terminal stage of cardiomyopathy.
PMID- 9657984
TI - Cloning and thermostability of TaqI endonuclease isoschizomers from Thermus
species SM32 and Thermus filiformis Tok6A1.
AB - Two TaqI endonuclease (hereafter referred to as TaqI) isoschizomer genes, tsp32IR
from Thermus species SM32 of Azores and tfiTok6A1I from T. filiformis Tok6A1 of
New Zealand, were cloned in Escherichia coli. The overexpressed enzymes were
partly purified and their thermostability was determined. In the medium-salt
buffer, Tsp32IR, TfiTok6A1I and one previously cloned TaqI isoschizomer (TthHB8I)
were more thermostable than TaqI. Tsp32IR remained partly active up to 90
degreesC in the low-salt buffer. Six amino acid residues that are identical in
the three high thermostability isoschizomers (Tsp32IR, TfiTok6A1I and TthHB8I)
but differ in TaqI might provide added rigidity for thermostabilization. These
include four proline residues located in or near loop regions, and one alanine
and one arginine located at helix regions in the predicted TaqI endonuclease
secondary structure. The possible role of these residues in thermostabilization
was evaluated by mutagenizing the TaqI enzyme. Mutants generated at these six
positions were less thermostable than wild-type TaqI. The results suggest that
the surrounding sequence or structural context might be as important as the
mutation itself.
PMID- 9657985
TI - Identification of a domain in apolipoprotein B-100 that inhibits the procoagulant
activity of tissue factor.
AB - The ability of low-density lipoprotein (LDL) to inhibit the procoagulant activity
of tissue factor is mediated by a direct protein-protein interaction involving
apolipoprotein (apo) B-100. A lysine-rich sequence within apo B-100 (residues
3121-3217), which we have termed lysine-rich apo B-100-derived (KRAD)-98 peptide,
may be responsible for its activity. Within this region, residues 3147-3160 (KRAD
14) contain an exceptionally high proportion of positive amino acids. Both
recombinant KRAD-98 and KRAD-14 peptides inhibited the procoagulant activity of
tissue factor by preventing the activation of factor VII. KRAD-14 also inhibited
the prothrombinase components, factors Xa and V. In comparison with the parent
protein (apo B-100), KRAD-14 peptide displayed a 20-fold enhancement in the rate
of inhibition, whereas KRAD-98 peptide exhibited a rate closer to that of apo B
100. Mutational analysis of KRAD-14 peptide revealed three adjacent amino acids,
alteration of which greatly reduced the inhibitory potential of this peptide. A
peptide derived from tissue factor (residues 58-66) was found to act co
operatively with tissue factor itself, but also augmented the inhibition of
tissue-factor activity by apo B-100. In conclusion, LDL may be a physiological
regulator of haemostatic mechanisms through the interactions of lysine-rich
domains of apo B-100 with tissue factor.
PMID- 9657986
TI - Recombinant human endothelin-converting enzyme ECE-1b is located in an
intracellular compartment when expressed in polarized Madin-Darby canine kidney
cells.
AB - Endothelin-converting enzyme (ECE) is a phosphoramidon-sensitive membrane-bound
metalloprotease responsible for the conversion of big-endothelins into
endothelins [Yanagisawa, Kurihara, Kimura, Tomobe, Kobayashi, Mitsui, Yazaki,
Goto and Masaki (1988) Nature (London) 332, 411-415]. Several distinct isoforms
of ECE have been cloned and identified. ECE-1a, b and c have the same ectodomain
and differ only by their cytosolic tails [Schweizer, Valdenaire, Nelbock,
Deuschle, Edwards, Stumpf and Loffler (1997) Biochem. J. 328, 871-877]. The
ectodomain common to ECE-1 a, b and c shares extensive sequence similarities with
neprilysin, a major kidney brush border metallopeptidase. To study the sorting of
ECE in polarized cells, ECE-1bcDNA was expressed by transfection in polarized
Madin-Darby canine kidney (MDCK) cells. Cell-surface biotinylation and
immunofluorescence studies showed that ECE-1b is not expressed on the cell
surface but was rather located in intracellular compartments that could also be
labelled with anti-Rab-5 and Rab-7 antibodies and was thus tentatively identified
as early and late endosomes. Similar results were also obtained when ECE-1b was
expressed in non-polarized Chinese hamster ovary cells for comparison purposes.
When MDCK or Chinese hamster ovary transfected cells were pre-treated with the
ECE inhibitor phosphoramidon, a 3-fold increase in the level of ECE-1b was
observed both by Western blotting and by enzymic activity. However, no change in
the level of neprilysin or the beta-chain of meprin, two apical membrane
metallopeptidases, was observed in MDCK cells transfected under similar
conditions. Northern blotting showed that the increase in the level of ECE-1b was
not owing to changes in the ECEmRNA transcription rate or stability. Rather,
pulse-chase experiments followed by immunoprecipitation showed a decrease in the
rate of degradation of ECE-1b in phosphoramidon-treated cells. Half-lives were
determined to be 2.8 and 7.5 h for non-treated and phosphoramidon-treated cells,
respectively. Confocal microscopy showed accumulation of ECE-1b immunoreactive
material in the lysosomes of phosphoramidon-treated cells. Taken together, these
results suggest that ECE-1b turns over very rapidly between endosomal and
lysosomal compartments and that lysosomal degradation of the enzyme is slowed
down by phosphoramidon.
PMID- 9657987
TI - Biosynthesis of mucins in bovine trachea: identification of the major
radiolabelled species.
AB - Bovine trachea in organ culture secretes mucus containing a 'high-density' (1.46
g/ml) and a 'low-density' (1.37 g/ml) mucin similar to those identified
previously in bovine respiratory secretions [Hovenberg, Carlstedt and Davies
(1997) Biochem. J. 321, 117-123]. After pulse-labelling, autoradiography showed
uptake of [35S]sulphate by both epithelial goblet cells and submucosal glands,
while [3H]proline was mainly incorporated into the ciliated surface epithelial
cells. After 24 h of radiolabelling, neither the high- nor the low-density mucin
in the secreted mucus gel was heavily radiolabelled with the precursors. In
contrast, a population of molecules banding at 1.50 g/ml was heavily
radiolabelled with [35S]sulphate. This component was smaller than the high
density mucin from the mucus gel and was insensitive to reduction or digestion
with chondroitin ABC lyase or heparan sulphate lyase. The molecules yielded two
populations of high-Mr glycopeptides upon trypsin digestion, were sensitive to
keratanase and endo-beta-galactosidase digestion and contained O-linked glycans.
Extracts of the surface epithelium and submucosal tissue after radiolabelling
showed that the high- and low-density mucins in the tissue were also poorly
radiolabelled. Thus, under these conditions, the radiolabelled precursors were
not effectively incorporated into the large oligomeric mucins but into a high-Mr
monomeric species. This study suggests that data obtained in investigations where
mucins are radiolabelled and studied without further separation into distinct
components may rather reflect the turnover of this 'novel' monomeric species than
the large oligomeric mucins.
PMID- 9657988
TI - What's for dinner?: Entner-Doudoroff metabolism in Escherichia coli.
PMID- 9657989
TI - Characterization of the maleylacetate reductase MacA of Rhodococcus opacus 1CP
and evidence for the presence of an isofunctional enzyme.
AB - Maleylacetate reductases (EC 1.3.1.32) have been shown to contribute not only to
the bacterial catabolism of some usual aromatic compounds like quinol or
resorcinol but also to the degradation of aromatic compounds carrying unusual
substituents, such as halogen atoms or nitro groups. Genes coding for
maleylacetate reductases so far have been analyzed mainly in chloroaromatic
compound-utilizing proteobacteria, in which they were found to belong to
specialized gene clusters for the turnover of chlorocatechols or 5
chlorohydroxyquinol. We have now cloned the gene macA, which codes for one of
apparently (at least) two maleylacetate reductases in the gram-positive,
chlorophenol-degrading strain Rhodococcus opacus 1CP. Sequencing of macA showed
the gene product to be relatively distantly related to its proteobacterial
counterparts (ca. 42 to 44% identical positions). Nevertheless, like the known
enzymes from proteobacteria, the cloned Rhodococcus maleylacetate reductase was
able to convert 2-chloromaleylacetate, an intermediate in the degradation of
dichloroaromatic compounds, relatively fast and with reductive dehalogenation to
maleylacetate. Among the genes ca. 3 kb up- and downstream of macA, none was
found to code for an intradiol dioxygenase, a cycloisomerase, or a dienelactone
hydrolase. Instead, the only gene which is likely to be cotranscribed with macA
encodes a protein of the short-chain dehydrogenase/reductase family. Thus, the R.
opacus maleylacetate reductase gene macA clearly is not part of a specialized
chlorocatechol gene cluster.
PMID- 9657990
TI - The glycyl radical enzyme TdcE can replace pyruvate formate-lyase in glucose
fermentation.
AB - Mutants of Escherichia coli unable to synthesize a functional pyruvate formate
lyase (PFL) are severely impaired in their capacity to grow by glucose
fermentation. In a functional complementation assay designed to isolate the pfl
gene from Clostridium butyricum, we fortuitously identified a gene that did not
encode a PFL but nonetheless was able to complement the phenotypic defects caused
by an E. coli pfl mutation. The clostridial gene encoded a basic 14. 5-kDa
protein (TcbC) which, based on amino acid similarity and analysis of immediately
adjacent DNA sequences, was part of a transposase exhibiting extensive similarity
to the product of the site-specific transposon Tn554 from Staphylococcus aureus.
Our studies revealed that the clostridial TcbC protein activated the
transcription of the E. coli tdcABCDEFG operon, which encodes an anaerobic L
threonine-degradative pathway. Normally, anaerobic synthesis of the pathway is
optimal when E. coli grows in the absence of catabolite-repressing sugars and in
the presence of L-threonine. Although anaerobic control of pathway synthesis was
maintained, TcbC alleviated glucose repression. One of the products encoded by
the tdc operon, TdcE, has recently been shown to be a 2-keto acid formate-lyase
(C. Hesslinger, S. A. Fairhurst, and G. Sawers, Mol. Microbiol. 27:477-492, 1998)
that can accept pyruvate as an enzyme substrate. Here we show that TdcE is
directly responsible for the restoration of fermentative growth to pfl mutants.
PMID- 9657991
TI - The apeE gene of Salmonella typhimurium encodes an outer membrane esterase not
present in Escherichia coli.
AB - Salmonella typhimurium apeR mutations lead to overproduction of an outer membrane
associated N-acetyl phenylalanine beta-naphthyl ester-cleaving esterase that is
encoded by the apeE gene (P. Collin-Osdoby and C. G. Miller, Mol. Gen. Genet.
243:674-680, 1994). This paper reports the cloning and nucleotide sequencing of
the S. typhimurium apeE gene as well as some properties of the esterase that it
encodes. The predicted product of apeE is a 69.9-kDa protein which is processed
to a 67-kDa species by removal of a signal peptide. The predicted amino acid
sequence of ApeE indicates that it is a member of the GDSL family of serine
esterases/lipases. It is most similar to a lipase excreted by the
entomopathogenic bacterium Photorhabdus luminescens. The Salmonella esterase
catalyzes the hydrolysis of a variety of fatty acid naphthyl esters and of C6 to
C16 fatty acid p-nitrophenyl esters but will not hydrolyze peptide bonds. A rapid
diagnostic test reported to be useful in distinguishing Salmonella spp. from
related organisms makes use of the ability of Salmonella to hydrolyze the
chromogenic ester substrate methyl umbelliferyl caprylate. We report that the
apeE gene product is the enzyme in Salmonella uniquely responsible for the
hydrolysis of this substrate. Southern blot analysis indicates that Escherichia
coli K-12 does not contain a close analog of apeE, and it appears that the apeE
gene is contained in a region of DNA present in Salmonella but not in E. coli.
PMID- 9657992
TI - Identification of cpxR as a positive regulator essential for expression of the
Shigella sonnei virF gene.
AB - virF is the master regulator which activates the virulence determinant genes of
Shigella spp. such as ipaBCD and virG. We previously reported that expression of
virF itself is regulated in a pH-dependent manner and that cpxA, a sensor of a
two-component regulatory system, is involved in this regulation (S. Nakayama and
H. Watanabe, J. Bacteriol. 177:5062-5069, 1995). Disruption of cpxR, which has
been thought to be the cognate response regulator of cpxA (J. Dong, S. Iuchi, H.
S. Kwan, Z. Lue, and E. C. C. Lin, Gene 136:227-230, 1993), abolished virF
expression almost completely. Purified CpxR bound directly to the upstream region
of virF. Binding capacity was enhanced when CpxR was phosphorylated by
coincubation with acetyl phosphate in vitro. Furthermore, we observed that
phosphorylated CpxR could activate virF transcription in vitro. These results
clearly indicated that CpxR was an essential activator for virF expression and
strongly suggested that the binding of phosphorylated CpxR to the target site
upstream of the virF gene induced a direct activation of virF transcription.
PMID- 9657993
TI - Regulation of biosynthesis of individual cellulases in Thermomonospora fusca.
AB - Regulation of the biosynthesis of the six cellulases comprising the cellulolytic
system of the thermophilic soil bacterium Thermomonospora fusca ER1 was studied.
The levels of the individual enzymes produced on different noninducing and
inducing carbon sources were determined. The lowest level of cellulase synthesis
(3 nM) was observed with xylose as a carbon source, and the highest level (247 to
1,670 nM for different enzymes) was found in cultures grown on microcrystalline
cellulose. Endocellulases and exocellulases showed distinctly different
regulation patterns. Differences in the regulation of individual enzymes appear
to be determined by the specific structural organization of the upstream
regulatory sequences of their genes.
PMID- 9657994
TI - Regulation of expression of GLT1, the gene encoding glutamate synthase in
Saccharomyces cerevisiae.
AB - Saccharomyces cerevisiae glutamate synthase (GOGAT) is an oligomeric enzyme
composed of three 199-kDa identical subunits encoded by GLT1. In this work, we
analyzed GLT1 transcriptional regulation. GLT1-lacZ fusions were prepared and
GLT1 expression was determined in a GDH1 wild-type strain and in a gdh1 mutant
derivative grown in the presence of various nitrogen sources. Null mutants
impaired in GCN4, GLN3, GAT1/NIL1, or UGA43/DAL80 were transformed with a GLT1
lacZ fusion to determine whether the above-mentioned transcriptional factors had
a role in GLT1 expression. A collection of increasingly larger 5' deletion
derivatives of the GLT1 promoter was constructed to identify DNA sequences that
could be involved in GLT1 transcriptional regulation. The effect of the lack of
GCN4, GLN3, or GAT1/NIL1 was also tested in the pertinent 5' deletion
derivatives. Our results indicate that (i) GLT1 expression is negatively
modulated by glutamate-mediated repression and positively regulated by Gln3p- and
Gcn4p-dependent transcriptional activation; (ii) two cis-acting elements, a
CGGN15CCG palindrome and an imperfect poly(dA-dT), are present and could play a
role in GLT1 transcriptional activation; and (iii) GLT1 expression is moderately
regulated by GCN4 under amino acid deprivation. Our results suggest that in a
wild-type strain grown on ammonium, GOGAT constitutes an ancillary pathway for
glutamate biosynthesis.
PMID- 9657995
TI - Expression of a gene for a porin-like protein of the OmpA family from
Mycobacterium tuberculosis H37Rv.
AB - An open reading frame in the genomic database of Mycobacterium tuberculosis H37Rv
was identified as having homology with an outer membrane protein. We found that
the gene specified a protein belonging to the OmpA family, which includes some
porins of gram-negative organisms. The gene was amplified by PCR and cloned into
Escherichia coli. Overexpression of the gene was toxic to the host, but limited
amounts could be purified from cells before growth ceased. A truncated gene
devoid of the code for a presumed signal sequence was well expressed, but the
protein had no pore-forming activity in the liposome swelling assay. However, the
intact protein, OmpATb, behaved as a porin of low specific activity, with a pore
diameter of 1.4 to 1.8 nm, and was also active in planar lipid bilayers, showing
a single-channel conductance of 700 pS. The protein had a molecular mass of about
38 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A polyclonal
rabbit antiserum raised to the truncated protein recognized a protein of similar
molecular mass in detergent extracts of broken M. tuberculosis cells. Reverse
transcription-PCR confirmed that the gene for OmpATb was expressed in M.
tuberculosis cells growing in culture. Comparison of the purified protein with
that in the detergent-extracted preparation using liposomes and planar lipid
bilayers showed that the two materials had similar pore-forming properties.
OmpATb is different from either of the mycobacterial porins described so far.
This is the first report of a porin-like molecule from M. tuberculosis; the porin
is likely to be important in controlling the access of hydrophilic molecules to
the bacterial cell.
PMID- 9657996
TI - Dual promoters are responsible for transcription initiation of the fla/che operon
in Bacillus subtilis.
AB - The fla/che region contains more than 30 genes required for flagellar synthesis
and chemotaxis in Bacillus subtilis, including the gene for the flagellum
specific sigmaD factor, sigD. Sequence and primer extension data demonstrate that
a PA promoter immediately upstream of flgB, henceforth referred to as the fla/che
PA, and the PD-3 promoter are active in vivo. Transcription from the PD-3 element
is dependent on sigmaD activity and is regulated by the flagellum-specific
negative regulator, FlgM. In a strain containing a deletion of fla/che PA
(PADelta), sigmaD protein was not detected, demonstrating that the fla/che PA is
necessary for wild-type expression of the sigD gene. Thus, sigD is part of the
>26-kb fla/che operon. Consistent with a lack of detectable sigmaD protein, the
PADelta strain grows as long filaments and does not express a sigmaD-dependent
hag::lacZ reporter construct. These phenotypes are indicative of a lack of sigD
expression or complete inhibition of sigmaD activity by FlgM. However, sigmaD
activity is found in a double mutant containing the PADelta and a null mutation
in flgM. The double mutant no longer grows as long filaments, and expression of
hag::lacZ is partially restored. These data demonstrate that a low level of
sigmaD activity does exist in the PADelta mutant but can be detected only in the
presence of a null mutation in flgM. Therefore, normal expression of sigD may
also involve another promoter(s) within the fla/che operon.
PMID- 9657997
TI - Roles of the carboxy-terminal half of Pseudomonas aeruginosa major outer membrane
protein OprF in cell shape, growth in low-osmolarity medium, and peptidoglycan
association.
AB - OprF, the major outer membrane protein of Pseudomonas aeruginosa, is
multifunctional in that it can act as a nonspecific porin, plays a role in the
maintenance of cell shape, and is required for growth in a low-osmolarity
environment. The latter two structural roles of OprF, and OprF's association with
the peptidoglycan, have been proposed to be localized in the carboxy terminus of
the protein, based on this region's similarity to members of the OmpA family of
proteins. To determine if this is correct, we constructed a series of C
terminally truncated OprF derivatives and examined their effects on P. aeruginosa
cell length and growth in low-osmolarity medium. While the C terminus of OprF was
required for wild-type cell length and growth in low-osmolarity medium,
expression of the N terminus (first 163 amino acids [aa]) also influenced these
phenotypes (compared with OprF deficiency). The first 154 to 164 aa of OprF
seemed required for stable protein expression, consistent with the existence of a
beta-barrel domain in the N terminus of OprF. Greater than 215 aa of the protein
were required for strong peptidoglycan association, confirming that residues in
the C-terminal end of OprF are required for peptidoglycan binding. OprF
deficiency did not affect the in vivo growth of an OprF-deficient strain in a
mouse chamber model. Collectively, these data suggest that the C terminus of OprF
plays a role in cell length, growth of P. aeruginosa in low-osmolarity media (but
not in vivo), and peptidoglycan association, while the N terminus has an
influence on the first two characteristics and is additionally important for
stable protein expression.
PMID- 9657998
TI - Proposed signal transduction role for conserved CheY residue Thr87, a member of
the response regulator active-site quintet.
AB - CheY serves as a structural prototype for the response regulator proteins of two
component regulatory systems. Functional roles have previously been defined for
four of the five highly conserved residues that form the response regulator
active site, the exception being the hydroxy amino acid which corresponds to
Thr87 in CheY. To investigate the contribution of Thr87 to signaling, we
characterized, genetically and biochemically, several cheY mutants with amino
acid substitutions at this position. The hydroxyl group appears to be necessary
for effective chemotaxis, as a Thr-->Ser substitution was the only one of six
tested which retained a Che+ swarm phenotype. Although nonchemotactic, cheY
mutants with amino acid substitutions T87A and T87C could generate clockwise
flagellar rotation either in the absence of CheZ, a protein that stimulates
dephosphorylation of CheY, or when paired with a second site-activating mutation,
Asp13-->Lys, demonstrating that a hydroxy amino acid at position 87 is not
essential for activation of the flagellar switch. All purified mutant proteins
examined phosphorylated efficiently from the CheA kinase in vitro but were
impaired in autodephosphorylation. Thus, the mutant CheY proteins are
phosphorylated to a greater degree than wild-type CheY yet support less clockwise
flagellar rotation. The data imply that Thr87 is important for generating and/or
stabilizing the phosphorylation-induced conformational change in CheY.
Furthermore, the various position 87 substitutions differentially affected
several properties of the mutant proteins. The chemotaxis and
autodephosphorylation defects were tightly linked, suggesting common structural
elements, whereas the effects on self-catalyzed and CheZ-mediated
dephosphorylation of CheY were uncorrelated, suggesting different structural
requirements for the two dephosphorylation reactions.
PMID- 9657999
TI - The D-xylose-binding protein, XylF, from Thermoanaerobacter ethanolicus 39E:
cloning, molecular analysis, and expression of the structural gene.
AB - Immediately downstream from the Thermoanaerobacter ethanolicus xylAB operon,
comprising genes that encode D-xylose isomerase and D-xylulose kinase, lies a
1,101-bp open reading frame that exhibits 61% amino acid sequence identity to the
Escherichia coli D-xylose binding periplasmic receptor, XylF, a component of the
high-affinity binding-protein-dependent D-xylose transport. The 25-residue N
terminal fragment of the deduced T. ethanolicus XylF has typical features of
bacterial leader peptides. The C-terminal portion of this leader sequence matches
the cleavage consensus for lipoproteins and is followed by a 22-residue putative
linker sequence rich in serine, threonine, and asparagine. The putative mature
341-amino-acid-residue XylF (calculated molecular mass of 37,069 Da) appears to
be a lipoprotein attached to the cell membrane via a lipid anchor covalently
linked to the N-terminal cysteine, as demonstrated by metabolic labelling of the
recombinant XylF with [14C]palmitate. The induced E. coli avidly bound D
[14C]xylose, yielding additional evidence that T. ethanolicus XylF is the D
xylose-binding protein. On the basis of sequence comparison of XylFs to other
monosaccharide-binding proteins, we propose that the sequence signature of
binding proteins specific for hexoses and pentoses be refined as
(KDQ)(LIVFAG)3IX3(DN)(SGP)X3(GS)X(LIVA) 2X2A. Transcription of the monocistronic
1.3-kb xylF mRNA is inducible by xylose and unaffected by glucose. Primer
extension analysis indicated that xylF transcription initiates from two +1 sites,
both situated within the xylAB operon. Unlike in similar transport systems in
other bacteria, the genes specifying the membrane components (e.g., ATP-binding
protein and permease) of the high-affinity D-xylose uptake system are not located
in the vicinity of xylF in T. ethanolicus. This is the first report of a gene
encoding a xylose-binding protein in a gram-positive or thermophilic bacterium.
PMID- 9658000
TI - A region in the Bacillus subtilis transcription factor Spo0A that is important
for spoIIG promoter activation.
AB - Spo0A is a DNA binding protein in Bacillus subtilis required for the activation
of spoIIG and other promoters at the onset of endospore formation. Activation of
some of these promoters may involve interaction of Spo0A and the sigmaA subunit
of RNA polymerase. Previous studies identified two single-amino-acid
substitutions in sigmaA, K356E and H359R, that specifically impaired Spo0A
dependent transcription in vivo. Here we report the identification of an amino
acid substitution in Spo0A (S231F) that suppressed the sporulation deficiency due
to the H359R substitution in sigmaA. We also found that the S231F substitution
partially restored use of the spoIIG promoter by the sigmaA H359R RNA polymerase
in vitro. Alanine substitutions in the 231 region of Spo0A revealed an additional
amino acid residue important for spoIIG promoter activation, I229. This amino
acid substitution in Spo0A did not affect repression of abrB transcription,
indicating that the alanine-substituted Spo0A was not defective in DNA binding.
Moreover, the alanine-substituted Spo0A protein activated the spoIIA promoter;
therefore, this region of Spo0A is probably not required for Spo0A-dependent,
sigmaH-directed transcription. These and other results suggest that the region of
Spo0A near position 229 is involved in sigmaA-dependent promoter activation.
PMID- 9658001
TI - Spo0A mutants of Bacillus subtilis with sigma factor-specific defects in
transcription activation.
AB - The transcription factor Spo0A of Bacillus subtilis has the unique ability to
activate transcription from promoters that require different forms of RNA
polymerase holoenzyme. One class of Spo0A-activated promoter, which includes
spoIIEp, is recognized by RNA polymerase associated with the primary sigma
factor, sigma A (sigmaA); the second, which includes spoIIAp, is recognized by
RNA polymerase associated with an early-sporulation sigma factor, sigma H
(sigmaH). Evidence suggests that Spo0A probably interacts directly with RNA
polymerase to activate transcription from these promoters. To identify residues
of Spo0A that may be involved in transcriptional activation, we used PCR
mutagenesis of the entire spo0A gene and designed a screen using two
distinguishable reporter fusions, spoIIE-gus and spoIIA-lacZ. Here we report the
identification and characterization of five mutants of Spo0A that are
specifically defective in activation of sigmaA-dependent promoters while
maintaining activation of sigmaH-dependent promoters. These five mutants identify
a 14-amino-acid segment of Spo0A, from residue 227 to residue 240, that is
required for transcriptional activation of sigmaA-dependent promoters. This
region may define a surface or domain of Spo0A that makes direct contacts with
sigmaA-associated holoenzyme.
PMID- 9658002
TI - Identification of a gene product induced by hard-surface contact of
Colletotrichum gloeosporioides conidia as a ubiquitin-conjugating enzyme by yeast
complementation.
AB - The germinating conidia of many phytopathogenic fungi on hosts must differentiate
into an infection structure called the appressorium in order to penetrate their
hosts. Chemical signals, such as the host's surface wax or fruit ripening
hormone, ethylene, trigger germination and appressorium formation of the avocado
pathogen Colletotrichum gloeosporioides only after the conidia are in contact
with a hard surface. What role this contact plays is unknown. Here, we describe
isolation of genes expressed during the early stage of hard-surface treatment by
a differential-display method and report characterization of one of these cloned
genes, chip1 (Colletotrichum hard-surface induced protein 1 gene), which encodes
a ubiquitin-conjugating enzyme. RNA blots clearly showed that it is induced by
hard-surface contact and that ethylene treatment enhanced this induction. The
predicted open reading frame (ubc1Cg) would encode a 16.2-kDa ubiquitin
conjugating enzyme, which shows 82% identity to the Saccharomyces cerevisiae UBC4
UBC5 E2 enzyme, comprising a major part of total ubiquitin-conjugating activity
in stressed yeast cells. UBC1Cg can complement the proteolysis deficiency of the
S. cerevisiae ubc4 ubc5 mutant, indicating that ubiquitin-dependent protein
degradation is involved in conidial germination and appressorial differentiation.
PMID- 9658003
TI - Circadian rhythm of nitrogenase gene expression in the diazotrophic filamentous
nonheterocystous cyanobacterium Trichodesmium sp. strain IMS 101.
AB - Recent studies suggested that the daily cycle of nitrogen fixation activity in
the marine filamentous nonheterocystous cyanobacterium Trichodesmium sp. is
controlled by a circadian rhythm. In this study, we evaluated the rhythm of
nitrogen fixation in Trichodesmium sp. strain IMS 101 by using the three criteria
for an endogenous rhythm. Nitrogenase transcript abundance oscillated with a
period of approximately 24 h, and the cycle was maintained even under constant
light conditions. The cyclic pattern of transcript abundance was maintained when
the culture was grown at 24 and 28.5 degrees C, although the period was slightly
longer (26 h) at the higher temperature. The cycle of gene expression could be
entrained with light-dark cues. Results of inhibitor experiments indicated that
transcript abundance was regulated primarily by transcription initiation, rather
than by degradation. The circadian rhythm, the first conclusively demonstrated
endogenous rhythm in a filamentous cyanobacterium, was also reflected in
nitrogenase MoFe protein abundance and patterns of Fe protein posttranslational
modification-demodification.
PMID- 9658004
TI - Copper-binding compounds from Methylosinus trichosporium OB3b.
AB - Two copper-binding compounds/cofactors (CBCs) were isolated from the spent media
of both the wild type and a constitutive soluble methane monooxygenase (sMMOC)
mutant, PP319 (P. A. Phelps et al., Appl. Environ. Microbiol. 58:3701-3708,
1992), of Methylosinus trichosporium OB3b. Both CBCs are small polypeptides with
molecular masses of 1,218 and 779 Da for CBC-L1 and CBC-L2, respectively. The
amino acid sequence of CBC-L1 is S?MYPGS?M, and that of CBC-L2 is SPMP?S. Copper
free CBCs showed absorption maxima at 204, 275, 333, and 356 with shoulders at
222 and 400 nm. Copper-containing CBCs showed a broad absorption maximum at 245
nm. The low-temperature electron paramagnetic resonance (EPR) spectra of copper
containing CBC-L1 showed the presence of a copper center with an EPR splitting
constant between those of type 1 and type 2 copper centers (g = 2.087, g = 2.42
G, A = 128 G). The EPR spectrum of CBC-L2 was more complex and showed two
spectrally distinct copper centers. One signal can be attributed to a type 2 Cu2+
center (g = 2.073, g = 2.324 G, A = 144 G) which could be saturated at higher
powers, while the second shows a broad, nearly isotropic signal near g = 2.063.
In wild-type strains, the concentrations of CBCs in the spent media were highest
in cells expressing the pMMO and stressed for copper. In contrast to wild-type
strains, high concentrations of CBCs were observed in the extracellular fraction
of the sMMOC mutants PP319 and PP359 regardless of the copper concentration in
the culture medium.
PMID- 9658005
TI - Lack of S-adenosylmethionine results in a cell division defect in Escherichia
coli.
AB - The enzyme S-adenosylmethionine (SAM) synthetase, the Escherichia coli metK gene
product, produces SAM, the cell's major methyl donor. We show here that SAM
synthetase activity is induced by leucine and repressed by Lrp, the leucine
responsive regulatory protein. When SAM synthetase activity falls below a certain
critical threshold, the cells produce long filaments with regularly distributed
nucleoids. Expression of a plasmid-carried metK gene prevents filamentation and
restores normal growth to the metK mutant. This indicates that lack of SAM
results in a division defect.
PMID- 9658006
TI - Differential regulation of Rhizobium etli rpoN2 gene expression during symbiosis
and free-living growth.
AB - The Rhizobium etli rpoN1 gene, encoding the alternative sigma factor sigma54
(RpoN), was recently characterized and shown to be involved in the assimilation
of several nitrogen and carbon sources during free-living aerobic growth (J.
Michiels, T. Van Soom, I. D'hooghe, B. Dombrecht, T. Benhassine, P. de Wilde, and
J. Vanderleyden, J. Bacteriol. 180:1729-1740, 1998). We identified a second rpoN
gene copy in R. etli, rpoN2, encoding a 54.0-kDa protein which displays 59% amino
acid identity with the R. etli RpoN1 protein. The rpoN2 gene is cotranscribed
with a short open reading frame, orf180, which codes for a protein with a size of
20.1 kDa that is homologous to several prokaryotic and eukaryotic proteins of
similar size. In contrast to the R. etli rpoN1 mutant strain, inactivation of the
rpoN2 gene did not produce any phenotypic defects during free-living growth.
However, symbiotic nitrogen fixation was reduced by approximately 90% in the
rpoN2 mutant, whereas wild-type levels of nitrogen fixation were observed in the
rpoN1 mutant strain. Nitrogen fixation was completely abolished in the rpoN1
rpoN2 double mutant. Expression of rpoN1 was negatively autoregulated during
aerobic growth and was reduced during microaerobiosis and symbiosis. In contrast,
rpoN2-gusA and orf180-gusA fusions were not expressed aerobically but were
strongly induced at low oxygen tensions or in bacteroids. Expression of rpoN2 and
orf180 was abolished in R. etli rpoN1 rpoN2 and nifA mutants under all conditions
tested. Under free-living microaerobic conditions, transcription of rpoN2 and
orf180 required the RpoN1 protein. In symbiosis, expression of rpoN2 and orf180
occurred independently of the rpoN1 gene, suggesting the existence of an
alternative symbiosis-specific mechanism of transcription activation.
PMID- 9658007
TI - RpoS (sigma-S) controls expression of rsmA, a global regulator of secondary
metabolites, harpin, and extracellular proteins in Erwinia carotovora.
AB - RpoS (sigma-S or sigma-38) controls a large array of genes that are expressed
during stationary phase and under various stress conditions in Escherichia coli
and other bacteria. We document here that plant pathogenic and epiphytic Erwinia
species, such as E. amylovora; E. carotovora subsp. atroseptica, betavasculorum,
and carotovora; E. chrysanthemi; E. herbicola; E. rhapontici; and E. stewartii,
possess rpoS genes and produce the alternate sigma factor. We show that rpoS
transcription in E. carotovora subsp. carotovora is driven from a major promoter
which resides within the nlpD gene located upstream of rpoS as in E. coli. RpoS-
E. carotovora subsp. carotovoa strain AC5061, constructed by marker exchange, is
more sensitive to hydrogen peroxide, carbon starvation, and acidic pH than its
RpoS+ parent strain, AC5006. The basal levels of extracellular pectate lyase,
polygalacturonase, and cellulase as well as those of transcripts of E. carotovora
subsp. carotovora hrpN (hrpNEcc), the gene for the elicitor of the hypersensitive
reaction, are higher in the RpoS- strain than in the RpoS+ parent. Likewise,
compared to AC5006, AC5061 causes more extensive maceration of celery petioles.
Our findings with the RpoS- mutant and strains carrying multiple copies rpoS+ DNA
reveal that rpoS positively controls rsmA expression. We also present evidence
that supports the hypothesis that the RpoS effect on extracellular enzyme levels,
hrpNEcc expression, and virulence manifests itself by the modulation of rsmA
expression.
PMID- 9658008
TI - Molecular characterization and postsplicing fate of three introns within the
single rRNA operon of the hyperthermophilic archaeon Aeropyrum pernix K1.
AB - The single rRNA operon (arnS-arnL) of the hyperthermophilic archaeon Aeropyrum
pernix K1 was sequenced. The DNA sequence data and detailed RNA analyses
disclosed an unusual feature: the presence of three introns at hitherto
undescribed insertion positions within the rRNA genes. The 699-nucleotide (nt)
intron Ialpha was located at position 908 (Escherichia coli numbering [H. F.
Noller, Annu. Rev. Biochem. 53:119-162, 1984]) of the 16S rRNA, while the 202-nt
intron Ibeta and 575-nt intron Igamma were located at positions 1085 and 1927 (E.
coli numbering), respectively, of the 23S rRNA. They were located within highly
conserved sites which have been implicated as crucial for rRNA function in E.
coli. All three introns were remarkably AT rich (41.5 to 43.1 mol% G+C) compared
with the mature rRNAs (67.7 and 69.2 mol% G+C for 16S and 23S rRNAs,
respectively). No obvious primary sequence similarities were detected among them.
After splicing from rRNA transcripts in vivo, a large quantity of intronic RNAs
were stably retained in the linear monomeric form, whereas a trace of
topoisomeric RNA molecules also appeared, as characterized by their behavior in
two-dimensional gel electrophoresis. Secondary structural models of the Ialpha-,
Ibeta-, and Igamma-containing rRNA precursors agree with the bulge-helix-bulge
motif. Two of the introns, Ialpha and Igamma, contained open reading frames whose
protein translation exhibited no overall similarity with proteins reported so
far. However, both share a LAGLI-DADG motif characteristic of homing
endonucleases.
PMID- 9658009
TI - Evidence of two oxidative reaction steps initiating anaerobic degradation of
resorcinol (1,3-dihydroxybenzene) by the denitrifying bacterium Azoarcus
anaerobius.
AB - The denitrifying bacterium Azoarcus anaerobius LuFRes1 grows anaerobically with
resorcinol (1,3-dihydroxybenzene) as the sole source of carbon and energy. The
anaerobic degradation of this compound was investigated in cell extracts.
Resorcinol reductase, the key enzyme for resorcinol catabolism in fermenting
bacteria, was not present in this organism. Instead, resorcinol was hydroxylated
to hydroxyhydroquinone (HHQ; 1,2,4-trihydroxybenzene) with nitrate or K3Fe(CN)6
as the electron acceptor. HHQ was further oxidized with nitrate to 2-hydroxy-1,4
benzoquinone as identified by high-pressure liquid chromatography, UV/visible
light spectroscopy, and mass spectroscopy. Average specific activities were 60 mU
mg of protein-1 for resorcinol hydroxylation and 150 mU mg of protein-1 for HHQ
dehydrogenation. Both activities were found nearly exclusively in the membrane
fraction and were only barely detectable in extracts of cells grown with
benzoate, indicating that both reactions were specific for resorcinol
degradation. These findings suggest a new strategy of anaerobic degradation of
aromatic compounds involving oxidative steps for destabilization of the aromatic
ring, different from the reductive dearomatization mechanisms described so far.
PMID- 9658010
TI - General stress transcription factor sigmaB and its role in acid tolerance and
virulence of Listeria monocytogenes.
AB - The gene encoding the general stress transcription factor sigmaB in the gram
positive bacterium Listeria monocytogenes was isolated with degenerate PCR
primers followed by inverse PCR amplification. Evidence for gene identification
includes the following: (i) phylogenetic analyses of reported amino acid
sequences for sigmaB and the closely related sigmaF proteins grouped L.
monocytogenes sigmaB in the same cluster with the sigmaB proteins from Bacillus
subtilis and Staphylococcus aureus, (ii) the gene order in the 2, 668-bp portion
of the L. monocytogenes sigB operon is rsbU-rsbV-rsbW-sigB-rsbX and is therefore
identical to the order of the last five genes of the B. subtilis sigB operon, and
(iii) an L. monocytogenes sigmaB mutant had reduced resistance to acid stress in
comparison with its isogenic parent strain. The sigB mutant was further
characterized in mouse models of listeriosis by determining recovery rates of the
wild-type and mutant strains from livers and spleens following intragastric or
intraperitoneal infection. Our results suggest that sigmaB-directed genes do not
appear to be essential for the spread of L. monocytogenes to mouse liver or
spleen at 2 and 4 days following intragastric or intraperitoneal infection.
PMID- 9658011
TI - Tca1, the retrotransposon-like element of Candida albicans, is a degenerate and
inactive element.
AB - Candida albicans is an asexual fungus and as such must rely on mechanisms other
than sexual recombination to generate genetic diversity. Retrotransposons are
ubiquitous genetic elements known to generate multiple types of genomic
alterations. We have further investigated the nature of the retrotransposon-like
element Tca1 in C. albicans. Tca1 is present at two loci in strain SC5314. Both
loci have now been cloned, and one element was sequenced in its entirety. This
element was flanked by alpha elements, or long terminal repeats (LTRs), and
contained an intervening region of 5,614 bp. The intervening region was highly
degenerate and contained no extended open reading frames, indicating that Tca1 is
not a functional element. Partial sequence determination demonstrated that the
elements from the two loci were nearly identical. Genetic manipulation of the
elements showed that both loci were heterozygous for Tca1, that both were
transcriptionally active, and that deletion of both had no effect on growth rate
or germ tube formation. Thus, it is unclear why this nonfunctional, highly
degenerate element has been maintained in many clinical isolates.
PMID- 9658012
TI - ftsE(Ts) affects translocation of K+-pump proteins into the cytoplasmic membrane
of Escherichia coli.
AB - The ftsE(Ts) mutation of Escherichia coli causes defects in cell division and
cell growth. We expressed alkaline phosphatase (PhoA) fusion proteins of KdpA,
Kup, and TrkH, all of which proved functional in vivo as K+ ion pumps, in the
mutant cells. During growth at 41 degrees C, these proteins were progressively
lost from the membrane fraction. The reduction in the abundance of these proteins
inversely correlated with cell growth, but the preformed proteins in the membrane
were stable at 41 degrees C, indicating that the molecules synthesized at the
permissive temperature were diluted in a growth-dependent manner at a high
temperature. Pulse-chase experiments showed that KdpA-PhoA was synthesized, but
the synthesized protein did not translocate into the membrane of the ftsE(Ts)
cells at 41 degrees C and degraded very rapidly. The loss of KdpA-PhoA from the
membrane fractions of ftsE(Ts) cells was suppressed by a multicopy plasmid
carrying the ftsE+ gene. While cell growth stopped when the abundance of these
proteins decreased 15-fold, the addition of a high concentration of K+ ions
specifically alleviated the growth defect of ftsE(Ts) cells but not cell
division, and the cells elongated more than 100-fold. We conclude that one of the
causes of growth cessation in the ftsE(Ts) mutants is a defect in the
translocation of K+-pump proteins into the cytoplasmic membrane.
PMID- 9658013
TI - Isolation and characterization of Bacillus subtilis sigB operon mutations that
suppress the loss of the negative regulator RsbX.
AB - sigmaB, a transcription factor that controls the Bacillus subtilis general stress
response regulon, is activated by either a drop in intracellular ATP or exposure
to environmental stress. RsbX, one of seven sigmaB regulators (Rsb proteins)
whose genes are cotranscribed with sigmaB, is a negative regulator in the stress
dependent activation pathway. To better define the interactions that take place
among the Rsb proteins, we analyzed sigB operon mutations which suppress the high
level sigmaB activity that normally accompanies the loss of RsbX. Each of these
mutations was in one of three genes (rsbT, -U, and -V) which encode positive
regulators of sigmaB, and they all defined amino acid changes which either
compromised the activities of the mutant Rsbs or affected their ability to
accumulate. sigmaB activity remained inducible by ethanol in several of the RsbX-
suppressor strains. This finding supports the notion that RsbX is not needed as
the target for sigmaB activation by at least some stresses. sigmaB activity in
several RsbX- strains with suppressor mutations in rsbT or -U was high during
growth and underwent a continued, rather than a transient, increase following
stress. Thus, RsbX is likely responsible for maintaining low sigmaB activity
during balanced growth and for reestablishing sigmaB activity at prestress levels
following induction. Although RsbX likely participates in limiting the sigmaB
induction response, a second mechanism for curtailing unrestricted sigmaB
activation was suggested by the sigmaB induction profile in two suppressor
strains with mutations in rsbV. sigmaB activity in these mutants was stress
inducible but transient, even in the absence of RsbX.
PMID- 9658014
TI - Low ubiquinone content in Escherichia coli causes thiol hypersensitivity.
AB - Thiol hypersensitivity in a mutant of Escherichia coli (IS16) was reversed by
complementation with a plasmid that carried the ubiX gene. The mutant had low
ubiquinone content. Complementation elevated the ubiquinone level and eliminated
thiol hypersensitivity. Analysis of chromosomal ubiX genes indicated that both
parent and mutant strains were ubiX mutants. The low ubiquinone content of IS16
was possibly caused by a ubiD ubiX genotype. A ubiA mutant also exhibited thiol
hypersensitivity. Neither IS16 nor the ubiA mutant strain could produce alkaline
phosphatase (in contrast to their parent strains) after 2 h of induction, thus
showing Dsb- phenotypes. The phenomena of thiol hypersensitivity and low
ubiquinone content may be linked by their connections to the periplasmic
disulfide bond redox machinery.
PMID- 9658015
TI - A periplasmic and extracellular c-type cytochrome of Geobacter sulfurreducens
acts as a ferric iron reductase and as an electron carrier to other acceptors or
to partner bacteria.
AB - An extracellular electron carrier excreted into the growth medium by cells of
Geobacter sulfurreducens was identified as a c-type cytochrome. The cytochrome
was found to be distributed in about equal amounts in the membrane fraction, the
periplasmic space, and the surrounding medium during all phases of growth with
acetate plus fumarate. It was isolated from periplasmic preparations and purified
to homogeneity by cation-exchange chromatography, gel filtration, and hydrophobic
interaction chromatography. The electrophoretically homogeneous cytochrome had a
molecular mass of 9.57 +/- 0.02 kDa and exhibited in its reduced state absorption
maxima at wavelengths of 552, 522, and 419 nm. The midpoint redox potential
determined by redox titration was -0.167 V. With respect to molecular mass, redox
properties, and molecular features, this cytochrome exhibited its highest
similarity to the cytochromes c of Desulfovibrio salexigens and Desulfuromonas
acetoxidans. The G. sulfurreducens cytochrome c reduced ferrihydrite (Fe(OH)3),
Fe(III) nitrilotriacetic acid, Fe(III) citrate, and manganese dioxide at high
rates. Elemental sulfur, anthraquinone disulfonate, and humic acids were reduced
more slowly. G. sulfurreducens reduced the cytochrome with acetate as an electron
donor and oxidized it with fumarate. Wolinella succinogenes was able to reduce
externally provided cytochrome c of G. sulfurreducens with molecular hydrogen or
formate as an electron donor and oxidized it with fumarate or nitrate as an
electron acceptor. A coculture could be established in which G. sulfurreducens
reduced the cytochrome with acetate, and the reduced cytochrome was reoxidized by
W. succinogenes in the presence of nitrate. We conclude that this cytochrome can
act as iron(III) reductase for electron transfer to insoluble iron hydroxides or
to sulfur, manganese dioxide, or other oxidized compounds, and it can transfer
electrons to partner bacteria.
PMID- 9658016
TI - Isolation and characterization of toluene-sensitive mutants from the toluene
resistant bacterium Pseudomonas putida GM73.
AB - To understand the mechanism underlying toluene resistance of a toluene-tolerant
bacterium, Pseudomonas putida GM73, we carried out Tn5 mutagenesis and isolated
eight toluene-sensitive mutants. None of the mutants grew in the presence of 20%
(vol/vol) toluene in growth medium but exhibited differential sensitivity to
toluene. When wild-type cells were treated with toluene (1% [vol/vol]) for 5 min,
about 2% of the cells could form colonies. In the mutants Ttg1, Ttg2, Ttg3, and
Ttg8, the same treatment killed more than 99.9999% of cells (survival rate, <10(
6)). In Ttg4, Ttg5, Ttg6, and Ttg7, about 0.02% of cells formed colonies. We
cloned the Tn5-inserted genes, and the DNA sequence flanking Tn5 was determined.
From comparison with a sequence database, putative protein products encoded by
ttg genes were identified as follows. Ttg1 and Ttg2 are ATP binding cassette
(ABC) transporter homologs; Ttg3 is a periplasmic linker protein of a toluene
efflux pump; both Ttg4 and Ttg7 are pyruvate dehydrogenase; Ttg5 is a
dihydrolipoamide acetyltransferase; and Ttg7 is the negative regulator of the
phosphate regulon. The sequences deduced from ttg8 did not show a significant
similarity to any DNA or proteins in sequence databases. Characterization of
these mutants and identification of mutant genes suggested that active efflux
mechanism and efficient repair of damaged membranes were important in toluene
resistance.
PMID- 9658017
TI - Molecular cloning and nucleotide sequence of the superoxide dismutase gene and
characterization of its product from Bacillus subtilis.
AB - Bacillus subtilis was found to possess one detectable superoxide dismutase (Sod)
in both vegetative cells and spores. The Sod activity in vegetative cells was
maximal at stationary phase. Manganese was necessary to sustain Sod activity at
stationary phase, but paraquat, a superoxide generator, did not induce the
expression of Sod. The specific activity of purified Sod was approximately 2, 600
U/mg of protein, and the enzyme was a homodimer protein with a molecular mass of
approximately 25,000 per monomer. The gene encoding Sod, designated sodA, was
cloned by the combination of several PCR methods and the Southern hybridization
method. DNA sequence analysis revealed the presence of one open reading frame
consisting of 606 bp. Several putative promoter sites were located in the
upstream region of sodA. The deduced amino acid sequence showed high homology
with other bacterial manganese Sods. Conserved regions in bacterial manganese Sod
could also be seen. The phenotype of double mutant Escherichia coli sodA sodB,
which could not grow in minimal medium without supplemental amino acids, was
complemented by the expression of B. subtilis sodA.
PMID- 9658018
TI - Sequence analysis of the GntII (subsidiary) system for gluconate metabolism
reveals a novel pathway for L-idonic acid catabolism in Escherichia coli.
AB - The presence of two systems in Escherichia coli for gluconate transport and
phosphorylation is puzzling. The main system, GntI, is well characterized, while
the subsidiary system, GntII, is poorly understood. Genomic sequence analysis of
the region known to contain genes of the GntII system led to a hypothesis which
was tested biochemically and confirmed: the GntII system encodes a pathway for
catabolism of L-idonic acid in which D-gluconate is an intermediate. The genes
have been named accordingly: the idnK gene, encoding a thermosensitive gluconate
kinase, is monocistronic and transcribed divergently from the idnD-idnO-idnT-idnR
operon, which encodes L-idonate 5-dehydrogenase, 5-keto-D-gluconate 5-reductase,
an L-idonate transporter, and an L-idonate regulatory protein, respectively. The
metabolic sequence is as follows: IdnT allows uptake of L-idonate; IdnD catalyzes
a reversible oxidation of L-idonate to form 5-ketogluconate; IdnO catalyzes a
reversible reduction of 5-ketogluconate to form D-gluconate; IdnK catalyzes an
ATP-dependent phosphorylation of D-gluconate to form 6-phosphogluconate, which is
metabolized further via the Entner-Doudoroff pathway; and IdnR appears to act as
a positive regulator of the IdnR regulon, with L-idonate or 5-ketogluconate
serving as the true inducer of the pathway. The L-idonate 5-dehydrogenase and 5
keto-D-gluconate 5-reductase reactions were characterized both chemically and
biochemically by using crude cell extracts, and it was firmly established that
these two enzymes allow for the redox-coupled interconversion of L-idonate and D
gluconate via the intermediate 5-ketogluconate. E. coli K-12 strains are able to
utilize L-idonate as the sole carbon and energy source, and as predicted, the
ability of idnD, idnK, idnR, and edd mutants to grow on L-idonate is altered.
PMID- 9658019
TI - The central, surface-exposed region of the flagellar hook protein FlgE of
Campylobacter jejuni shows hypervariability among strains.
AB - In a previous study, we observed that monoclonal antibodies raised against the
hook protein FlgE of Campylobacter jejuni LIO 36, isolate 5226, bound exclusively
to this strain. The aim of this study was to elucidate the molecular basis for
these binding specificities. The hook protein-encoding gene flgE of C. jejuni was
cloned in Escherichia coli and sequenced. The flgE genes of four additional C.
jejuni strains were amplified by PCR and also sequenced. Comparison of the
deduced amino acid sequences revealed a high degree of variability in the central
parts of the FlgE proteins among the strains, including variable and
hypervariable domains. These findings may indicate a selective pressure of C.
jejuni hosts, forcing the bacteria to generate variations in surface-exposed
antigenic determinants.
PMID- 9658020
TI - Temperature regulation of heat-labile enterotoxin (LT) synthesis in Escherichia
coli is mediated by an interaction of H-NS protein with the LT A-subunit DNA.
AB - Protein and mRNA levels of heat-labile enterotoxin (LT) of Escherichia coli are
highest at 37 degrees C, and they decrease gradually as temperature is decreased.
This temperature effect is eliminated in an Hns- mutant. Deletion of portions of
DNA coding for the LT A subunit also results in an increase in LT expression at
low temperatures, suggesting that the H-NS protein causes inhibition of
transcription at low temperatures by interacting with the LT A-subunit DNA. The
region that interacts with H-NS is referred to as the downstream regulatory
element (DRE). Plasmids in an hns strain from which the DRE has been deleted
still produce elevated levels of LT at 18 degrees C, suggesting that intact DRE
is not required for transcription from the LT promoter.
PMID- 9658021
TI - Diversity of cytochrome bc complexes: example of the Rieske protein in green
sulfur bacteria.
AB - The Rieske 2Fe2S cluster of Chlorobium limicola forma thiosulfatophilum strain
tassajara was studied by electron paramagnetic resonance spectroscopy. Two
distinct orientations of its g tensor were observed in oriented samples
corresponding to differing conformations of the protein. Only one of the two
conformations persisted after treatment with 2,5-dibromo-3-methyl-6-isopropyl-p
benzoquinone. A redox midpoint potential (Em) of +160 mV in the pH range of 6 to
7.7 and a decreasing Em (-60 to -80 mV/pH unit) above pH 7.7 were found. The
implications of the existence of differing conformational states of the Rieske
protein, as well as of the shape of its Em-versus-pH curve, in green sulfur
bacteria are discussed.
PMID- 9658022
TI - Opposing roles of the Staphylococcus aureus virulence regulators, Agr and Sar, in
Triton X-100- and penicillin-induced autolysis.
AB - The regulation of murein hydrolases is a critical aspect of peptidoglycan growth
and metabolism. In the present study, we demonstrate that mutations within the
Staphylococcus aureus virulence factor regulatory genes, agr and sar, affect
autolysis, resulting in decreased and increased autolysis rates, respectively.
Zymographic analyses of these mutant strains suggest that agr and sar exert their
effects on autolysis, in part, by modulating murein hydrolase expression and/or
activity.
PMID- 9658023
TI - A minisatellite sequence within the propeptide region of the vacuolar
carboxypeptidase Y gene of Schizosaccharomyces pombe.
AB - We describe the presence of a minisatellite sequence that displays length
polymorphisms in the fission yeast Schizosaccharomyces pombe. The minisatellite
sequence was found to reside within the propeptide region of the vacuolar
carboxypeptidase Y gene. The minisatellite sequence, which was found only at a
single locus, was mitotically stable and displayed length polymorphisms between
the two varieties of S. pombe (S. pombe var. pombe and S. pombe var.
malidevorans). The minisatellite sequence, however, appeared to be species
specific and was absent in other members of the Schizosaccharomyces genus. This
report constitutes the first experimental demonstration of the presence of such
sequences in yeasts.
PMID- 9658024
TI - General stress transcription factor sigmaB and sporulation transcription factor
sigmaH each contribute to survival of Bacillus subtilis under extreme growth
conditions.
AB - The general stress response of the bacterium Bacillus subtilis is controlled by
the sigmaB transcription factor. Here we show that loss of sigmaB reduces
stationary-phase viability 10-fold in either alkaline or acidic media and reduces
cell yield in media containing ethanol. We further show that loss of the
developmental transcription factor sigmaH also has a marked effect on stationary
phase viability under these conditions and that this effect is independent from
the simple loss of sporulation ability.
PMID- 9658025
TI - Predictive reward signal of dopamine neurons.
AB - The effects of lesions, receptor blocking, electrical self-stimulation, and drugs
of abuse suggest that midbrain dopamine systems are involved in processing reward
information and learning approach behavior. Most dopamine neurons show phasic
activations after primary liquid and food rewards and conditioned, reward
predicting visual and auditory stimuli. They show biphasic, activation-depression
responses after stimuli that resemble reward-predicting stimuli or are novel or
particularly salient. However, only few phasic activations follow aversive
stimuli. Thus dopamine neurons label environmental stimuli with appetitive value,
predict and detect rewards and signal alerting and motivating events. By failing
to discriminate between different rewards, dopamine neurons appear to emit an
alerting message about the surprising presence or absence of rewards. All
responses to rewards and reward-predicting stimuli depend on event
predictability. Dopamine neurons are activated by rewarding events that are
better than predicted, remain uninfluenced by events that are as good as
predicted, and are depressed by events that are worse than predicted. By
signaling rewards according to a prediction error, dopamine responses have the
formal characteristics of a teaching signal postulated by reinforcement learning
theories. Dopamine responses transfer during learning from primary rewards to
reward-predicting stimuli. This may contribute to neuronal mechanisms underlying
the retrograde action of rewards, one of the main puzzles in reinforcement
learning. The impulse response releases a short pulse of dopamine onto many
dendrites, thus broadcasting a rather global reinforcement signal to postsynaptic
neurons. This signal may improve approach behavior by providing advance reward
information before the behavior occurs, and may contribute to learning by
modifying synaptic transmission. The dopamine reward signal is supplemented by
activity in neurons in striatum, frontal cortex, and amygdala, which process
specific reward information but do not emit a global reward prediction error
signal. A cooperation between the different reward signals may assure the use of
specific rewards for selectively reinforcing behaviors. Among the other
projection systems, noradrenaline neurons predominantly serve attentional
mechanisms and nucleus basalis neurons code rewards heterogeneously. Cerebellar
climbing fibers signal errors in motor performance or errors in the prediction of
aversive events to cerebellar Purkinje cells. Most deficits following dopamine
depleting lesions are not easily explained by a defective reward signal but may
reflect the absence of a general enabling function of tonic levels of
extracellular dopamine. Thus dopamine systems may have two functions, the phasic
transmission of reward information and the tonic enabling of postsynaptic
neurons.
PMID- 9658026
TI - Neuronal responses related to smooth pursuit eye movements in the periarcuate
cortical area of monkeys.
AB - To examine how the periarcuate area is involved in the control of smooth pursuit
eye movements, we recorded 177 single neurons while monkeys pursued a moving
target in the dark. The majority (52%, 92/177) of task-related neurons responded
to pursuit but had little or no response to saccades. Histological
reconstructions showed that these neurons were located mainly in the posterior
bank of the arcuate sulcus near the sulcal spur. Twenty-seven percent (48/177)
changed their activity at the onset of saccades. Of these, 36 (75%) showed
presaccadic burst activity with strong preference for contraversive saccades.
Eighteen (10%, 18/177) were classified as eye-position-related neurons, and 11%
(19/177) were related to other aspects of the stimuli or response. Among the 92
neurons that responded to pursuit, 85 (92%) were strongly directional with
uniformly distributed preferred directions. Further analyses were performed in
these directionally sensitive pursuit-related neurons. For 59 neurons that showed
distinct changes in activity around the initiation of pursuit, the median latency
from target motion was 96 ms and that preceding pursuit was -12 ms, indicating
that these neuron can influence the initiation of pursuit. We tested some neurons
by briefly extinguishing the tracking target (n = 39) or controlling its movement
with the eye position signal (n = 24). The distribution of the change in pursuit
related activity was similar to previous data for the dorsomedial part of the
medial superior temporal neurons (, indicating that pursuit-related neurons in
the periarcuate area also carry extraretinal signals. For 22 neurons, we examined
the responses when the animals reversed pursuit direction to distinguish the
effects of eye acceleration in the preferred direction from oppositely directed
eye velocity. Almost all neurons discharged before eye velocity reached zero,
however, only nine neurons discharged before the eyes were accelerated in the
preferred direction. The delay in neuronal responses relative to the onset of eye
acceleration in these trials might be caused by suppression from oppositely
directed pursuit velocity. The results suggest that the periarcuate neurons do
not participate in the earliest stage of eye acceleration during the change in
pursuit direction, although most of them may participate in the early stages of
pursuit initiation in the ordinary step-ramp pursuit trials. Some neurons changed
their activity when the animals fixated a stationary target, and this activity
could be distinguished easily from the strong pursuit-related responses. Our
results suggest that the periarcuate pursuit area carries extraretinal signals
and affects the premotor circuitry for smooth pursuit.
PMID- 9658027
TI - Modulation of the inspiratory-related activity of hypoglossal premotor neurons
during ingestion and rejection in the decerebrate cat.
AB - Single-unit activities of the bulbar reticular inspiratory neurons directly
projecting to hypoglossal motoneurons were studied during fictive ingestion
(e.g., swallowing) and rejection elicited by repetitive stimulation of the
superior laryngeal nerve and by application of water to the pharynx in
immobilized decerebrated cats. The single-unit activity was recorded during 113
episodes of fictive ingestion from 25 inspiratory neurons directly projecting to
hypoglossal motoneurons (single projection neurons) and 7 inspiratory neurons
directly projecting to both hypoglossal and phrenic motoneurons (dual projection
neurons) in the regions ventrolateral to the nucleus tractus solitarii and
dorsomedial to the nucleus ambiguus. All of single projection neurons ceased
inspiratory-related rhythmical discharges coincidentally with the onset of
repetitive stimulation of the superior laryngeal nerve. The majority of them
(19/25, 76%, type A) showed a spike burst during ingestion, whereas the minority
(6/25, 24%, type B) kept silent until the end of repetitive stimulation of the
superior laryngeal nerve. During fictive ingestion elicited by application of
water to the pharynx, the type-A neurons showed a spike burst activity, whereas
the type-B neurons kept silent. All dual projection neurons (7/7, 100%, type C)
ceased inspiratory-related rhythmical discharges at the onset of repetitive
stimulation of the superior laryngeal nerve and showed no activity during fictive
ingestion. Likewise, the type-C neurons kept silent during fictive ingestion
elicited by application of water to the pharynx. A spike burst was induced during
33 episodes of fictive rejection in all of 5 tested type-A, 3 tested type-B, and
6 tested type-C neurons. It is concluded that the premotor neurons involved in
the respiratory-related rhythmical activity of hypoglossal motoneurons is
responsible for switching from respiration to ingestion and rejection.
PMID- 9658028
TI - Primate red nucleus discharge encodes the dynamics of limb muscle activity.
AB - We studied the dynamical relationship between magnocellular red nucleus (RNm)
discharge and electromyographic (EMG) activity of 10-15 limb muscles in two
monkeys during voluntary limb movement. Recordings were made from 158 neurons
during two different kinds of limb movement tasks. One was a tracking task in
which the subjects were required to acquire targets displayed on an oscilloscope
by rotating one of six different single degree of freedom manipulanda. During
this task, we recorded the angular position of the manipulandum. The monkeys also
were trained in several free-form food-retrieval tasks that were much less
constrained mechanically. There was generally significantly greater neuronal
discharge during the free-form tasks than during the tracking task. During both
types of tasks, cross-correlation and impulse response functions calculated
between RNm and EMG were predominantly pulse-shaped, indicating that the dynamics
of the RNm discharge were very similar to those of the muscle activity. There was
no evidence during either task for a substantial dynamical transformation (e.g.,
integration) between the two signals as had been previously suggested. In only
15% of the cases, did these correlations have step or pulse-step dynamics. There
was a relatively broad, unimodal distribution of lag times between RNm and EMG,
based on the time of occurrence of the peak correlation. During tracking, the
mode of this distribution was approximately 50 ms, with 80% of the lags falling
between -100 and 200 ms. During the free-form task, the mode was between 0 and 20
ms, with 65% of the lags between -100 and 200 ms. A positive lag indicates that
RNm discharge preceded EMG. The shape and timing of both the cross-correlation
and the impulse response functions were consistent with a model in which many RNm
neurons contribute mutually correlated signals which are simply summed within the
spinal cord to produce a muscle activation signal.
PMID- 9658029
TI - GABAergic and glycinergic inhibition sharpens tuning for frequency modulations in
the inferior colliculus of the big brown bat.
AB - Discrimination of amplitude and frequency modulated sounds is an important task
of auditory processing. Experiments have shown that tuning of neurons to
sinusoidally frequency- and amplitude-modulated (SFM and SAM, respectively)
sounds becomes successively narrower going from lower to higher auditory brain
stem nuclei. In the inferior colliculus (IC), many neurons are sharply tuned to
the modulation frequency of SFM sounds. The purpose of this study was to
determine whether GABAergic or glycinergic inhibition is involved in shaping the
tuning for the modulation frequency of SFM sounds in IC neurons of the big brown
bat (Eptesicus fuscus). We recorded the response of 56 single units in the
central nucleus of the IC to SFM stimuli before and during the application of the
gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline or the glycine
receptor antagonist strychnine. To evaluate tuning to the modulation frequency,
the normalized spike count (normalized according to the maximal response for each
condition tested) was plotted versus the modulation frequency and the upper and
lower 50% cutoff points were determined. Bicuculline increased the upper cutoff
in 46% of the neurons by >/=25%. The lower cutoff decreased in 48% of the neurons
tested. In some neurons (approximately 30%), a sharpening of the tuning by
bicuculline was observed. Strychnine induced an increase of the upper cutoff in
almost half of the neurons. Compared with bicuculline these changes were smaller.
The lower cutoff decreased in 50% of the neurons with strychnine. The
synchronization coefficient (SC) was calculated and compared for three modulation
frequencies (50, 100, and 200 Hz) between predrug and drug condition. For all
neurons, synchronization decreased (n = 36) or did not change (n = 26) during
drug application. This was mainly an effect of the prolonged discharge in
response to each cycle. Under predrug conditions, many neurons exhibited
selectivity to the direction of the FM, hence they only responded once to each
cycle. In a minority of neurons, direction selectivity was abolished by drug
application. The main finding was that neuronal inhibition sharpens tuning to the
modulation frequency in the majority of neurons. In general, changes induced by
bicuculline or strychnine were comparable.
PMID- 9658030
TI - Full weight-bearing hindlimb standing following stand training in the adult
spinal cat.
AB - Behavioral and physiological characteristics of standing were studied in
nontrained spinal cats and in spinal cats that received daily stand training of
the hindlimbs for 12 wk. Training consisted of assisting the cats to stand with
full weight support either on both hindlimbs or on one hindlimb (30 min/day, 5
days/wk). Extensor muscle electromyographic (EMG) amplitude and extension at the
knee and ankle joints during full weight bearing recovered to prespinal levels in
both stand-trained and nontrained spinal cats. However, full weight bearing of
the hindquarters was sustained for up to approximately 20 min in the spinal cats
that received bilateral stand training compared with approximately 4 min in cats
that were not trained to stand. Unilateral stand training selectively improved
weight bearing on the trained limb based on ground reaction forces and extensor
muscle EMG activity levels measured during bilateral standing. These results
suggest that the capacity of the adult lumbar spinal cord to generate full weight
bearing standing can be improved by as much as fivefold by the repetitive
activation of selected neural pathways in the spinal cord after supraspinal
connectivity has been eliminated. Given that stepping is improved in response to
step training, it appears that the recovery of standing provides another example
of training-specific motor learning in the spinal cord, i.e., the spinal cord
learns to perform hindlimb standing by practicing that specific task.
PMID- 9658031
TI - Characterization of neuronal migration disorders in neocortical structures. II.
Intracellular in vitro recordings.
AB - Neuronal migration disorders (NMD) are involved in a variety of different
developmental disturbances and in therapy-resistant epilepsy. The cellular
mechanisms underlying the pronounced hyperexcitability in dysplastic cortex are
not well understood and demand further clinical and experimental analyses. We
used a focal freeze-lesion model in cerebral cortex of newborn rats to study the
functional consequences of NMD. Intracellular recordings from supragranular
regular spiking cells in cortical slices from adult sham-operated rats revealed
normal passive and active intrinsic membrane properties and normal stimulus
evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs,
respectively). Regular spiking neurons recorded in rat dysplastic cortex showed
on average a significantly smaller action potential amplitude, a slower spike
rise, and a less steep primary frequency-current relationship. Stimulus-elicited
EPSPs in NMD-affected cortex consisted of multiphasic burst discharges, which
coincided with extracellular field potentials and lasted 150-800 ms. These
epileptiform responses could be recorded at membrane potentials between -50 and
110 mV and were blocked by -2-amino-5-phosphonovaleric acid (APV), indicating the
involvement of N-methyl--aspartate (NMDA) receptors. Isolated NMDA-mediated and
APV-sensitive EPSPs could be recorded at membrane potentials negative to -70 mV,
suggesting that NMDA receptors are activated at relatively negative membrane
potentials. In comparison with the controls, polysynaptic IPSPs mediated by the
gamma-aminobutyric acid (GABA) type A and B receptor were either absent or
reduced in peak conductance in microgyric cortex by 27% (P < 0.05) and 17%,
respectively. However, monosynaptic IPSPs recorded in the presence of ionotropic
glutamate receptor antagonists revealed a similar efficacy in NMD and control
cortex, indicating that GABAergic neurons in microgyric cortex get a weaker
excitatory input. Our data indicate that the expression of epileptiform activity
in NMD-affected cortex rather results from an imbalance between excitatory and
inhibitory synaptic transmission than from alterations in the intrinsic membrane
properties. This imbalance is caused by an increase in NMDA-receptor-mediated
excitation in pyramidal neurons and a concurrent decrease of glutamatergic input
onto inhibitory interneurons.
PMID- 9658032
TI - Differential effects of the reticulospinal system on locomotion in lamprey.
AB - Specific effects of stimulating different parts of the reticulospinal (RS) system
on the spinal locomotor pattern are described in lamprey. In the in vitro brain
stem and spinal cord preparation, microstimulation in different areas of the
reticular formation was performed by ejecting a small amount of -glutamate from a
micropipette. These areas were distributed over the four reticular nuclei of the
brain stem: the mesencephalic reticular nucleus (MRN) and the anterior, middle
and posterior rhombencephalic reticular nuclei (ARRN, MRRN, and PRRN,
respectively). To prevent synaptic spread of excitation within the brain stem,
the synaptic transmission was blocked by using a low Ca2+, high Mn2+
physiological saline in the brain stem pool. "Fictive" locomotion was evoked by
applying N-methyl--aspartate (NMDA) to the spinal cord. Rhythmical discharges of
motoneurons were recorded bilaterally in the midbody area, from the ventral roots
that had been subdivided in dorsal and ventral branches, supplying the dorsal and
ventral part of the myotome, respectively. Two major effects of brain stem
stimulation were elicited: a change in the frequency of the locomotory rhythm and
an induction of asymmetry (left/right, dorsal/ventral) in the segmental motor
output. Approximately 50% of the stimulated sites evoked a change in locomotor
frequency. In the PRRN almost all effective sites evoked an increase in frequency
(10-50%). In the other nuclei, increase and decrease (10-30%) were observed
equally frequently. Most of the stimulated sites (50-80%) in any reticular
nucleus evoked asymmetry in the segmental motor output. Distortion of the
segmental output symmetry was classified into eight categories by comparing the
intensity of locomotor bursts in the dorsal and ventral branches of the two
ventral roots, ipsilateral and contralateral to the stimulated side. These
categories differed in the direction of the body flexion, which would be evoked
during normal swimming: ipsilateral (I), contralateral (C), dorsal (D), ventral
(V), ipsilateral and dorsal (ID), ipsilateral and ventral (IV), contralateral and
dorsal (CD), and contralateral and ventral (CV). The different categories were
not equally represented in each nucleus and across the nuclei. The most
pronounced categories for each nucleus were as follow. In MRN: I (33%); ARRN: C
(44%); MRRN: rostral part, I (36%) and caudal part, CV (42%); and PRRN: rostral
part, I (40%) and caudal part, IV (35%). Other categories were also present but
less common in each nucleus. To examine if the effects of brain stem stimulation
were uniform along the spinal cord, recordings were performed from distal parts
of the cord. Stimulation of a given point in the brain stem produced similar
pattern of effects in 59% of cases and different patterns in 41% of cases. The
main conclusion of the present study is that the proportion of RS neurons with
different influences on the spinal locomotor network differs significantly among
different parts of the reticular formation of the lamprey. The specificity of RS
influences may represent a basis for modifications of the segmental locomotor
output necessary for the control of equilibrium and steering during locomotion.
PMID- 9658033
TI - Substance P enhances NMDA channel function in hippocampal dentate gyrus granule
cells.
AB - Substance P (SP)-containing afferents and the NK-1 tachykinin receptor to which
SP binds are present in the dentate gyrus of the rat; however, direct actions of
SP on principal cells have not been demonstrated in this brain region. We have
examined the effect of SP on N-methyl--aspartate (NMDA) channels from acutely
isolated dentate gyrus granule cells of adult rat hippocampus to assess the
ability of SP to regulate glutamatergic input. SP produces a robust enhancement
of single NMDA channel function that is mimicked by the NK-1-selective agonist
Sar9, Met(O2)11-SP. The SP-induced prolongation of NMDA channel openings is
prevented by the selective NK-1 receptor antagonist (+)-(2S, 3S)-3-(2
methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Calcium influx or activation
of protein kinase C were not required for the SP-induced increase in NMDA channel
open durations. The dramatic enhancement of excitatory amino acid-mediated
excitability by SP places this neuropeptide in a key position to gate activation
of hippocampal network activity.
PMID- 9658034
TI - Control of size and excitability of mechanosensory receptive fields in dorsal
column nuclei by homolateral dorsal horn neurons.
AB - Both accidental and experimental lesions of the spinal cord suggest that neuronal
processes occurring in the spinal cord modify the relay of information through
the dorsal column-lemniscal pathway. How such interactions might occur has not
been adequately explained. To address this issue, the receptive fields of
mechanosensory neurons of the dorsal column nuclei were studied before and after
manipulation of the spinal dorsal horn. After either a cervical or lumbar
laminectomy and exposure of the dorsal column nuclei in anesthetized cats, the
representation of the hindlimb or of the forelimb was defined by multiunit
recordings in both the dorsal column nuclei and in the ipsilateral spinal cord.
Next, a single cell was isolated in the dorsal column nuclei, and its receptive
field carefully defined. Each cell could be activated by light mechanical stimuli
from a well-defined cutaneous receptive field. Generally the adequate stimulus
was movement of a few hairs or rapid skin indentation. Subsequently a pipette
containing either lidocaine or cobalt chloride was lowered into the ipsilateral
dorsal horn at the site in the somatosensory representation in the spinal cord
corresponding to the receptive field of the neuron isolated in the dorsal column
nuclei. Injection of several hundred nanoliters of either lidocaine or cobalt
chloride into the dorsal horn produced an enlargement of the receptive field of
the neuron being studied in the dorsal column nuclei. The experiment was repeated
16 times, and receptive field enlargements of 147-563% were observed in 15 cases.
These data suggest that the dorsal horn exerts a tonic inhibitory control on the
mechanosensory signals relayed through the dorsal column-lemniscal pathway.
Because published data from other laboratories have shown that receptive field
size is controlled by signals arising from the skin, we infer that the control of
neuronal excitability, receptive field size and location for lemniscal neurons is
determined by tonic afferent activity that is relayed through a synapse in the
dorsal horn. This influence of dorsal horn neurons on the relay of mechanosensory
information through the lemniscal pathways must modify our traditional views
concerning the relative independence of these two systems.
PMID- 9658035
TI - Physiological signs of the activation of bag2 and chain intrafusal muscle fibers
of gastrocnemius muscle spindles in the cat.
AB - A method is described for identifying the effect of single gamma static
(gamma(s)) axons on bag2 or chain intrafusal fibers using random (Poisson
distributed) stimuli. The cross-correlogram of the stimuli with the firing of
spindle primary afferents took one of three forms. A large, simple, brief
response was taken to indicate pure chain fiber activation and a small, prolonged
response to indicate pure bag2 activation. A compound response with brief and
prolonged components was taken to be a sign of mixed innervation. The correlogram
components could be well fitted with lognormal curves. They could also be
transformed into curves of gain as a function of frequency, which were convenient
for estimating the strength of the effects. In 68 effects of gammas axons on Ia
afferents, 16 were pure chain, 17 pure bag2, and 35 mixed. This distribution was
significantly different (P < 0. 05) from that expected from chance nonspecific
innervation of chain and bag2 fibers. Making use of the estimates of the strength
of chain and bag2 effects derived from the gain curves, the classification was
modified by treating mixed responses that had one effect more than five times
stronger than the other as belonging to the dominant type. The distribution was
then as follows: chain 16, bag2 28, and mixed 24. This differed very
significantly from the prediction of chance distribution (P < 0.001). This
evidence for some degree of specific innervation of chain and bag2 fibers is
discussed in relation to previous work and with regard to the ways in which the
two fiber types might be used in natural movements.
PMID- 9658036
TI - Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor
function at the developing corticothalamic synapse.
AB - The development of receptor function at corticothalamic synapses during the first
20 days of postnatal development is described. Whole cell excitatory postsynaptic
currents (EPSCs) were evoked in relay neurons of the ventral posterior nucleus
(VP) by stimulation of corticothalamic fibers in in vitro slices of mouse brain
from postnatal day 1 (P1). During P1-P12, excitatory postsynaptic conductances
showed strong voltage dependence at peak current and at 100 ms after the stimulus
and were almost completely antagonized by -2-amino-5-phosphonopentoic acid (APV),
indicating that N-methyl--aspartate (NMDA) receptor-mediated currents dominate
corticothalamic EPSCs at this time. After P12, in 42% of cells, excitatory
postsynaptic conductances showed no voltage-dependence at peak current but still
showed voltage-dependence 100-ms poststimulus. This voltage-dependent conductance
was antagonized by APV. The nonvoltage-dependent component was APV resistant,
showed fast decay, and was antagonized by the nonNMDA antagonist, 6-cyano-7
nitroquinoxaline-2,3-dione (CNQX). In the remaining 58% of cells after P12,
excitatory postsynaptic conductances showed moderate voltage dependence at peak
conductance and strong voltage dependence 100 ms after the stimulus. Analysis of
EPSCs before and after APV showed a significant increase in the relative
contribution of the non-NMDA conductance after the second postnatal week. From P1
to P16, there was a significant decrease in the time constant of decay of the
NMDA EPSC but no change in the voltage dependence of the NMDA response. After P8,
slow EPSPs, 1.5-30 s in duration and mediated by metabotropic glutamate receptors
(mGluRs), could be evoked by high-frequency stimulation of corticothalamic fibers
in the presence of APV and CNQX. Similar slow depolarizations could be evoked by
local application of the mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3
dicarboxylic acid (t-ACPD) but from P0. Both conductances were blocked by the
mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine. Hence functional
mGluR receptors are present on VP cells from birth, but their synaptic activation
at corticothalamic synapses can only be detected after P8. In voltage clamp, the
extrapolated reversal potential of the t-ACPD current, with potassium gluconate
based internal solution, was +12 +/- 10 (SE) mV, and the measured reversal
potential with cesium gluconate-based internal solution was 1.5 +/- 9.9 mV,
suggesting that the mGluR-mediated depolarization was mediated by a nonselective
cation current. Replacement of NaCl in the external solution caused the reversal
potential of the current to shift to -18 +/- 2 mV, indicating that Na+ is a
charge carrier in the current. The current amplitude was not reduced by
application of Cs+, Ba2+, and Cd2+, indicating that the t-ACPD current was
distinct from the hyperpolarization-activated cation current (IH) and distinct
from certain other previously characterized mGluR-activated, nonselective cation
conductances.
PMID- 9658037
TI - Limbic gamma rhythms. I. Phase-locked oscillations in hippocampal CA1 and
subiculum.
AB - Gamma oscillations (approximately 40 Hz) were induced in transverse hippocampal
slices by tetanic stimulation of CA1 and/or subiculum. Tetanic stimulation of
each site elicited population gamma oscillations in the surrounding tissue <400
micro(m) away. Stimulation of CA1 alone could evoke activity at both CA1 and
subiculum. Subicular stimulation, however, did not transmit to CA1. When the
rostral end of CA1 was stimulated, gamma oscillations transmitted across <1.5 mm
of silent CA1 before reappearing in the subiculum. Tetanic stimulation of CA1
increased [K+]o to 8.2 +/- 1.5 mM (mean +/- SE). The location of the peak
increase corresponded to the site of local gamma generation. Silent areas of CA1
experienced smaller [K+]o increases, to 4.9 +/- 0.7 mM. The subiculum, which
generated gamma, remained at the baseline 3.0 mM. Although fluctuations in [K+]o
may have an impact on the generation of gamma rhythms, they are not necessary for
them. Gamma oscillations had similar frequencies in CA1 and subiculum (40.4 +/-
2.9 and 43.9 +/- 3.1 Hz, respectively). When present in both, the oscillations
typically were phase locked with the subiculum lagging by 5.4 +/- 1.8 ms. When
both CA1 and subiculum were stimulated the lag decreased by 28%. These delays
approximate those expected for the conduction velocity of axons between the two
regions, here estimated at 0.52 +/- 0.07 m/s. Transmission of gamma oscillations
from CA1 to subiculum was blocked by the focal addition of the alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionic acid-receptor antagonist, 6-nitro-7
sulfamoylbenzo[f]quinoxaline-2,3-dione, to the subiculum. Oscillations induced in
CA1 by local tetanic stimulation were blocked by focal application of the gamma
aminobutyric acid-A (GABAA) receptor antagonist, bicuculline, to CA1. Focal
application of bicuculline to the subiculum blocked gamma due to subicular
stimulation but not that due to CA1 stimulation. Bath-applied bicuculline
disrupted subicular gamma evoked by subicular stimulation and led to a transient
period of epileptiform responses before completely blocking responses. The
further addition of the GABAB receptor antagonist, CGP 55845A, reversed this
block, restoring the epileptic discharges evoked by tetanic stimulation. This
suggests that the subiculum differs from hippocampal CA3 and neocortex, in having
a powerful GABAB receptor-dependent mechanism to prevent epileptic discharges.
The subiculum generates gamma rhythms both in response to local stimulation and
to gamma rhythms evoked in CA1. Subicular gamma differs from that in CA1 in the
presence of population spike doublets rather than singlets on many cycles. In
both areas, generation of gamma by local stimulation depends on GABAA receptors,
suggesting that the subiculum shares the interneuronal network mechanism we
proposed for CA1.
PMID- 9658038
TI - Limbic gamma rhythms. II. Synaptic and intrinsic mechanisms underlying spike
doublets in oscillating subicular neurons.
AB - Gamma oscillations were evoked in the subiculum in rat transverse hippocampal
slices by tetanic stimulation (200 ms/100 Hz) of either CA1 or subiculum. Gamma
oscillations in the subiculum differed from those in CA1 in containing population
spike doublets as well as singlets. The present study addresses the origin of
this more complex form of gamma oscillation in the subiculum. Intracellular
recordings from subicular neurons revealed that 63% of them fired double action
potentials on cycles of the gamma oscillation that generated population spike
doublets after tetanic stimulation of either CA1 or subiculum. The remaining
cells produced excitatory postsynaptic potentials (EPSPs), and occasional single
spikes, on each cycle. Neurons that fired occasional single action potentials
during gamma rhythms were "regular spiking" cells. They did not produce burst
discharges during depolarizing steps, had minimal membrane potential sags on
hyperpolarizing steps, and responded to single afferent volleys with a single
action potential on an EPSP followed by a large inhibitory postsynaptic potential
complex. Fast spiking cells were observed too infrequently to be studied in
detail. Neurons that fired doublets during gamma rhythms were "intrinsic burst"
(IB) cells. They generated bursts of action potentials on step membrane
depolarizations, had significant membrane potential sags on step
hyperpolarizations with an anodal break potential on return to rest, and fired
multiple action potentials in response to high-intensity single afferent volleys.
IB neurons did not fire action potential doublets during 1-s membrane
depolarizations. Double action potentials, however, were evoked in these cells by
depolarizing pulses at 40 Hz from hyperpolarized membrane potentials (-100 mV).
Computer simulations suggest that the hyperpolarization between the
depolarizations was essential for action potential doublets. The results in this
and the previous paper suggest the following: either CA1 or subiculum alone can
generate gamma oscillations gated by local networks of interneurons, oscillations
in CA1 project through pyramidal cell axons to subiculum with a time lag expected
from axon conduction delays, and oscillating sequences of EPSPs and intrinsic
and/or synaptic hyperpolarizing potentials in IB subicular neurons generate gamma
frequency spike doublets, which depend on both the intrinsic properties of these
neurons and their temporally patterned synaptic input. This phenomenon could
amplify gamma output from CA1 and modify its coupling to gamma oscillations in
the wider limbic system.
PMID- 9658039
TI - GABAergic inhibition influences auditory motion-direction sensitivity in barn
owls.
AB - Many neurons in the barn owl's inferior colliculus (IC) exhibit auditory motion
direction sensitivity (MDS), i.e., they respond more to motion of a sound source
in one direction than to motion in the opposite direction. We investigated the
cellular mechanisms underlying the phenomenon of auditory MDS by
microiontophoretically applying gamma-aminobutyric acid (GABA) or the GABA
antagonist bicuculline methiodide (BMI) while recording from neurons in the owl's
midbrain. In most cases GABA reduced the overall firing rate, whereas BMI
increased it. In addition, 29% of the motion-direction-sensitive cells completely
lost their selectivity for the direction of auditory movement during
administration of BMI. It had been proposed that auditory MDS in the owl is due
to inhibition. The present results show that GABAergic inhibition plays a role in
the strengthening of MDS. We discuss the data within the framework of the
acoustic motion detector and with respect to microiontophoretic studies on visual
motion detection and on inhibitory mechanisms in the inferior colliculus.
PMID- 9658040
TI - Effects of mitochondrion on calcium transients at intact presynaptic terminals
depend on frequency of nerve firing.
AB - The rate and the total amount of Ca2+ elevation in the presynaptic terminals of
bullfrog sympathetic ganglia depend on the firing frequency of the terminals.
Carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, was
used for testing whether mitochondrial Ca2+ uptake is one of the mechanisms that
underlie this frequency dependence. Fura-2 fluorimetry was used for measurement
of intraterminal Ca2+. When stimulations of different durations (30 and 1.5 s)
and frequencies (4 and 20 Hz) evoked Ca2+ transients with similar peak amplitudes
(264 +/- 22 nM vs. 251 +/- 18 nM, means +/- SE), CCCP augmented the responses to
the 4-Hz stimulation 8.9 times more strongly than it did the responses to the 20
Hz stimulation (249.7 +/- 81.5% vs. 25.3 +/- 10.2%). When stimulations delivered
at the two frequencies had the same durations (1.5, 3, 6, 10, 20, and 30 s), CCCP
enlarged the responses to the 4-Hz stimulations up to 4.2 times more than it did
the responses to the 20-Hz stimulations. When the same number of stimuli (120)
was delivered at the two frequencies, the effects of CCCP on the responses evoked
by the 4-Hz train were again 6.8 times stronger than its effects on the responses
to the 20-Hz stimulation. Therefore neither the peak amplitudes of the responses
nor the durations of the stimulations dictated the extent to which the
mitochondria modulated the peak [Ca2+]i. Instead, the extent of the modulation
was governed by the frequency of stimulation. Specifically, the less frequent the
Ca2+ influx, the stronger the mitochondrial modulation. Also, during nerve firing
Ca2+ release from the ryanodine-sensitive store had a higher potential to
influence the [Ca2+]i transients than did Ca2+ removal by the mitochondria for
the first 6 s of the responses. On cessation of stimulation, CCCP reduced the
initial rapid rate of Ca2+ decay. Thus uptake by the mitochondria was an
important mechanism for Ca2+ removal after repetitive firing at the presynaptic
terminals.
PMID- 9658041
TI - Endogenous NMDA-receptor activation regulates glutamate release in cultured
spinal neurons.
AB - N-methyl--aspartate (NMDA) receptor activation plays a fundamental role in the
genesis of electrical activity of immature neurons and may participate in
activity-dependent aspects of CNS development. A recent study has suggested that
NMDA-receptor-mediated glutamatergic neurotransmission might occur in the
developing spinal cord via activation of nonsynaptic receptors, but the details
of NMDA-receptor activation in the developing CNS are not yet well understood. We
describe here a model of cultured spinal neurons that display ongoing alpha-amino
3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity
characterized by spontaneous excitatory postsynaptic currents (EPSCs), with NMDA
receptor activity detectable only as single channel events. -2-amino-5
phosphonovaleric acid (100 microM) and tetrodotoxin (TTX) 100 nM each reduced the
occurrence of spontaneous AMPA EPSCs; quantal analysis showed a decrease in the
number of released quanta but no changes in quantal size, indicating that NMDA
receptor activation and Na+ channel activity affect the generation of spontaneous
AMPA EPSCs, at least in part, via mechanisms that impinge on the presynaptic
terminal. Once the Mg2+-block was released, activity of NMDA receptors
dramatically increased the release of quantal and multiquantal amounts of
glutamate, indicating that the NMDA receptors are physiologically coupled to
glutamate release. In Mg2+-free solution, TTX application elicited an increase in
the number of quantal AMPA EPSCs and a reduction in the number of multiquantal
EPSCs, consistent with an effect of NMDA-receptor activation on presynaptic
terminals. Our results suggest that endogenous activity at a small number of NMDA
receptors can regulate the release of neurotransmitters at developing AMPA
synapses.
PMID- 9658042
TI - Metabotropic glutamate receptor activation modulates sound level processing in
the cochlear nucleus.
AB - The principal role of ionotropic glutamate receptors in the transmission and
processing of information in the auditory pathway has been investigated
extensively. In contrast, little is known about the functional contribution of
the G-protein-coupled metabotropic glutamate receptors (mGluRs), although their
anatomic location suggests that they exercise a significant influence on auditory
processing. To investigate this issue, sound-evoked responses were obtained from
single auditory neurons in the cochlear nuclear complex of anesthetized cats and
gerbils, and metabotropic ligands were administered locally through
microionophoretic pipettes. In general, microionophoresis of the mGluR agonists,
(1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S, 2'S)-2
(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous
and sound-evoked discharge rates. However, activation and recovery times were
significantly longer than those observed for ionotropic agonists, such as N
methyl--aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,
consistent with the recruitment of a second-messenger system. The efficacy of
mGluR agonists was diminished after administration of the mGluR antagonist, (+)
alpha-methyl-4-carboxyphenylglycine, consistent with a selective action at
metabotropic recognition sites. In contrast, two distinct changes were observed
after the mGluR agonist had been discontinued for several minutes. Approximately
50% of neurons exhibited a chronic depression of sound-evoked discharge rate
reminiscent of long-term depression, a cellular property observed in other
systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the
sound-evoked response similar to the cellular phenomenon of long-term
potentiation. These findings suggest that mGluR activation has a profound
influence on the gain of primary afferent driven activity in the caudal cochlear
nucleus.
PMID- 9658043
TI - Substance P-induced inward current in identified auditory efferent neurons in rat
brain stem slices.
AB - The effects of substance P (SP) on whole cell currents were studied in neurons of
the medial olivocochlear efferent system (MOCS) in the ventral nucleus of the
trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was
identified by retrograde labeling with Fast Blue injected into the cochlea. Bath
application of SP (0.1-10 microM) reversibly induced an apparent inward current
in 49 of 63 labeled neurons when voltage clamped at near resting voltages. This
apparent inward current was consistent with the SP-induced membrane
depolarization observed in current-clamp mode. The SP-induced change in current
was dose dependent with a half-maximal response dose of 200 nM. It was mimicked
by [Cys3,6, Tyr8, Pro9]-SP, a neurokinin (NK1) receptor selective agonist,
whereas [Succinyl-Asp6, MePhe8]-SP 6-11 (Senktide), a NK3 receptor agonist, had
no detectable effect. The SP effect was not blocked by 10(-6) M tetrodotoxin
(TTX) and persisted when the perfusate contained 30 mM tetraethylammonium (TEA)
or 100 microM Cd2+ or was in a 0-Ca solution. In a TTX-containing solution, SP
caused a voltage-dependent decrease of membrane conductance, and the SP-evoked
current reversed at a potential at around -105 mV. The predicted K+ equilibrium
potential was -93.8 mV under the experimental conditions. The SP-induced inward
current was attenuated by 66% when the perfusate contained 3 mM Cs+. We conclude
that the apparent inward current is partly caused by SP decreasing an outward
current normally maintained by the inward rectifier K+ channels in these cells.
In the presence of Cs solution in the recording pipette and with a perfusate
containing 3 mM Cs+, 0.1 mM Cd2+ and 10(-6) M TTX, a residual SP-induced inward
current was observed at test voltages ranging from -120 to 40 mV. This
subcomponent reversed its polarity at approximately 20 mV. This inward current
was reduced substantially (but not abolished) when all NaCl in the external
solution was replaced by TEA-Cl. The results indicate that SP also opens an
unknown cation channel, which the available data suggests may be relatively
nonselective. The results suggest that MOCS neurons are subject to modulation by
SP, which depolarizes the cell membrane by decreasing the activity of inward
rectifier K+ channels as well as concurrently activating a separate cation
conductance. It also was found that in MOCS neurons responsive to both SP and
norepinephrine, the norepinephrine effect was abolished by TTX, suggesting that
an interneuronal population excited by norepinephrine converges selectively onto
SP-sensitive MOCS neurons in the VNTB.
PMID- 9658044
TI - Responses of deep entorhinal cortex are epileptiform in an electrogenic rat model
of chronic temporal lobe epilepsy.
AB - We investigated whether entorhinal cortex (EC) layer IV neurons are
hyperexcitable in the post-selfsustaining limbic status epilepticus (post-SSLSE)
animal model of temporal lobe epilepsy. We studied naive rats (n = 44), epileptic
rats that had experienced SSLSE resulting in spontaneous seizures (n = 45), and
electrode controls (n = 7). There were no differences between electrode control
and naive groups, which were pooled into a single control group. Intracellular
and extracellular recordings were made from deep layers of EC, targeting layer
IV, which was activated by stimulation of the superficial layers of EC or the
angular bundle. There were no differences between epileptic and control neurons
in basic cellular characteristics, and all neurons were quiescent under resting
conditions. In control tissue, 77% of evoked intracellular responses consisted of
a short-duration [8.6 +/- 1.3 (SE) ms] excitatory postsynaptic potential and a
single action potential followed by gamma-aminobutyric acid-A (GABAA) and GABAB
inhibitory post synaptic potentials (IPSPs). Ten percent of controls did not
contain IPSPs. In chronically epileptic tissue, evoked intracellular responses
demonstrated prolonged depolarizing potentials (256 +/- 39 ms), multiple action
potentials (13 +/- 4), and no IPSPs. Ten percent of epileptic responses were
followed by rhythmic "clonic" depolarizations. Epileptic responses exhibited an
all-or-none response to progressive increases in stimulus intensity and required
less stimulation to elicit action potentials. In both epileptic and control
animals, intracellular responses correlated precisely in morphology and duration
with extracellular field potentials. Severing the hippocampus from the EC did not
alter the responses. Duration of intracellular epileptic responses was reduced
22% by the N-methyl--aspartate (NMDA) antagonist (-)-2-amino-5-phosphonovaleric
acid (APV), but they did not return to normal and IPSPs were not restored.
Epileptic and control responses were abolished by the non-NMDA antagonist 6, 7
dinitroquinoxaline-2-3-dione (DNQX). A monosynaptic IPSP protocol was used to
test connectivity of inhibitory interneurons to primary cells by direct
activation of interneurons with a stimulating electrode placed near the recording
electrode in the presence of APV and DNQX. Using this protocol, IPSPs similar to
control (P > 0.05) were seen in epileptic cells. The findings demonstrate that
deep layer EC cells are hyperexcitable or "epileptiform" in this model.
Hyperexcitability is not due to interactions with the hippocampus. It is due
partially to augmented NMDA-mediated excitation. The lack of IPSPs in epileptic
neurons may suggest inhibition is impaired, but we found evidence that inhibitory
interneurons are connected to their target cells and are capable of inducing
IPSPs.
PMID- 9658045
TI - Distribution of effective synaptic currents in cat triceps surae motoneurons. VI.
Contralateral pyramidal tract.
AB - We measured the effective synaptic currents (IN) produced by stimulating the
contralateral pyramidal tract (PT) in triceps surae motoneurons of the cat. This
is an oligosynaptic pathway in the cat that generates both excitation and
inhibition in hindlimb motoneurons. We also determined the effect of the PT
synaptic input on the discharge rate of some of the motoneurons by inducing
repetitive firing with long, injected current pulses during which the PT
stimulation was repeated. At resting potential, all but one triceps motoneuron
received a net depolarizing effective synaptic current from the PT stimulation.
The effective synaptic currents (IN) were much larger in putative type F
motoneurons than in putative type S motoneurons [+4.6 +/- 2.9 (SD) nA for type F
vs. 0.9 +/- 2.4 nA for putative type S]. When the values of IN at the threshold
for repetitive firing were estimated, the distribution was markedly altered. More
than 60% of the putative type S motoneurons received a net hyperpolarizing
effective synaptic current from the pyramidal tract stimulation as did 33% of the
putative type F motoneurons. This distribution pattern is very similar to that
observed previously for the effective synaptic currents produced by stimulating
the contralateral red nucleus. As would be expected from the wide range of IN
values at threshold (-4.8 to +8.7 nA), the PT stimulation produced dramatically
different effects on the discharge of different triceps motoneurons. The
discharge rates of those motoneurons that received depolarizing effective
synaptic currents at threshold were accelerated by PT stimulation (+1 to +8
imp/s), whereas the discharge rates of cells that received hyperpolarizing
currents were retarded by the PT input (-2 to -7 imp/s). The change in firing
rates produced by the PT stimulation was generally approximated by the product of
the effective synaptic currents and the slopes of the motoneurons' frequency
current relations. Our findings indicate that the contralateral pyramidal tract
may provide a powerful source of synaptic drive to some high-threshold
motoneurons while concurrently inhibiting low-threshold cells. Thus this input
system, like that from the contralateral red nucleus, can potentially alter the
gain of the input-output function of the motoneuron pool as well as disrupt the
normal hierarchy of recruitment thresholds.
PMID- 9658046
TI - Comparison of static fusimotor innervation in cat peroneus tertius and longus
muscles.
AB - Static fusimotor innervation was compared in cat peroneus longus and tertius
muscles because the gamma to spindle ratio is considerably higher in the longus
(approximately 60 gamma axons for 17 spindles) than in the tertius (approximately
24 gamma axons for 14 spindles). Single gamma axons were identified as static
(gamma(s)) by their typical effects on the response of primary ending to ramp
stretch. The intrafusal muscle fibers that single gamma(s) axons activated in the
spindles they supplied were identified by the features of cross-correlograms
between Ia impulses and stimuli, at 100 Hz, and by those of primary ending
responses during stimulation at 30 Hz. In each experiment, a large proportion of
the gamma population was tested on about nine spindles. A statistical analysis
was used to estimate the number of spindles supplied by single gamma(s) axons and
the proportion of gamma(s) axons that supply only one spindle among those the
stimulation of which had activated either bag2 or chain fibers alone in a single
spindle. In peroneus longus, nearly all gamma(s) axons supply one or two
spindles, whereas in peroneus tertius, the majority of gamma(s) axons supply from
three to six spindles. The proportion of nonspecifically distributed gamma(s)
axons, i.e., of axons that supply both bag2 fibers and chain fibers either in the
same or in different spindles, is much lower (56%) in the longus than in the
tertius (83%) as previously observed on a population of gammas axons that
supplied from three to six spindles. Correspondingly, the proportion of specific
axons is much higher in the longus (44%) than in the tertius (17%). In none of
the two muscles was a strict relationship observed between the conduction
velocity of gamma(s) axons and their intrafusal distribution (specific bag2,
specific chain fibers, nonspecific). However, gamma(s) supplying bag2 fibers
either specifically or in combination with chain fibers tended to have faster
conduction velocities, which suggests that, in various motor acts, the proportion
of activated bag2 and chain fibers may be related to the proportions of activated
fast and slow gamma(s) axons.
PMID- 9658047
TI - Analysis of rapid stopping during human walking.
AB - The mechanisms involved in rapidly terminating human gait were studied. Subjects
were asked to walk at a comfortable speed and to stop walking as soon as they
felt an electrical stimulus to the superficial peroneal nerve. This simulated
hitting an obstacle with the top of the foot. Stimuli were presented repeatedly
at random during a 20-min period of walking. Electromyograms and joint angular
movements of the right leg and forces under both feet were recorded. The step
cycle was divided into 16 parts, and the responses to stimuli in each part were
analyzed separately. Subjects generally stopped with the right foot in front of
the left or vice-versa, depending on when the stimulus was applied in the step
cycle. There was also a transition region in which subjects would rise up on
their toes and either back down or take one more quick, short forward step. Three
different mechanisms were used to produce a stop. 1) An extension synergy in the
swing leg was initiated just before this leg hit the ground to brake the forward
momentum of the body. 2) The push-off phase of the stance leg was inhibited to
reduce the forward thrust and maintain the stance leg on the ground behind the
body. 3) If these mechanisms were insufficient, the body rose up onto the toes of
the extended forward leg and thereby converted more kinetic energy to potential
energy. A decision to take an additional step depends on whether the momentum of
the body is sufficient to carry the center of mass in front of its support on the
forward leg. If so, an additional step is taken. Despite the complexity of the
decisions that must be made, changes in electromyographic activity are seen
throughout the legs and trunk in 150-200 ms.
PMID- 9658048
TI - Noise from voltage-gated ion channels may influence neuronal dynamics in the
entorhinal cortex.
AB - Neurons of the superficial medial entorhinal cortex (MEC), which deliver
neocortical input to the hippocampus, exhibit intrinsic, subthreshold
oscillations with slow dynamics. These intrinsic oscillations, driven by a
persistent Na+ current and a slow outward current, may help to generate the theta
rhythm, a slow rhythm that plays an important role in spatial and declarative
learning. Here we show that the number of persistent Na+ channels underlying
subthreshold oscillations is relatively small (<10(4)) and use a physiologically
based stochastic model to argue that the random behavior of these channels may
contribute crucially to cellular-level responses. In acutely isolated MEC neurons
under voltage clamp, the mean and variance of the persistent Na+ current were
used to estimate the single channel conductance and voltage-dependent probability
of opening. A hybrid stochastic-deterministic model was built by using voltage
clamp descriptions of the persistent and fast-inactivating Na+ conductances,
along with the fast and slow K+ conductances. All voltage-dependent conductances
were represented with nonlinear ordinary differential equations, with the
exception of the persistent Na+ conductance, which was represented as a
population of stochastic ion channels. The model predicts that the probabilistic
nature of Na+ channels increases the cell's repertoire of qualitative behaviors;
although deterministic models at a particular point in parameter space can
generate either subthreshold oscillations or phase-locked spikes (but rarely
both), models with an appropriate level of channel noise can replicate
physiological behavior by generating both patterns of electrical activity for a
single set of parameters. Channel noise may contribute to higher order interspike
interval statistics seen in vitro with DC current stimulation. Models with
channel noise show evidence of spike clustering seen in brain slice experiments,
although the effect is apparently not as prominent as seen in experimental
results. Channel noise may contribute to cellular responses in vivo as well; the
stochastic system has enhanced sensitivity to small periodic stimuli in a form of
stochastic resonance that is novel (in that the relevant noise source is
intrinsic and voltage-dependent) and potentially physiologically relevant.
Although based on a simple model that does not include all known membrane
mechanisms of MEC stellate cells, these results nevertheless imply that the
stochastic nature of small collections of molecules may have important effects at
the cellular and network levels.
PMID- 9658050
TI - Response to motion in extrastriate area MSTl: center-surround interactions.
AB - The medial superior temporal area of the macaque monkey extrastriate visual
cortex can be divided into a dorsal medial (MSTd) and a lateral ventral (MSTl)
region. The functions of the two regions may not be identical: MSTd may process
optic flow information that results from the movement of the observer, whereas
MSTl may be related more closely to processing visual motion related specifically
to the motion of objects. If MSTl were related to such object motion, one would
expect to see mechanisms for the segregation of objects from their surround. We
investigated one of these mechanisms in MSTl neurons: the effect of stimuli
falling in the region surrounding the receptive field center on the response to
stimuli falling in the field center. We found the effects of the surround
stimulation to be modulatory with little response to the surround stimulus itself
but a clear effect on the response to the stimulus falling on the receptive field
center. The response to motion in the center in the direction preferred for the
neuron usually increased when the surround motion was in the opposite direction
to that in the center and decreased when surround motion was in the same
direction as that in the center. Fifty-seven percent of the neurons showed a
ratio of response for center motion with a surround moving in the opposite
direction to that in the center for center motion alone that was >1. The response
to motion in the center also increased when the surround stimulus was stationary,
and this increase was sometimes larger than that with a moving surround. Nearly
70% of the neurons showed a ratio of response to center motion with a stationary
surround to center motion alone that was >1. This is in contrast to the minimal
effect of stationary surrounds in middle temporal area neurons. When the stimulus
presentation was reversed so that the stimulus in the center was stationary and
the surround moved, some MSTl neurons responded when the direction of motion in
the surround was in the direction opposite to the preferred direction of motion
in the center of the receptive field. Stimulation of the surround thus had a
profound effect on the response of MSTl neurons, and this pronounced effect of
the surround is consistent with a role in the segmentation of objects using
motion.
PMID- 9658049
TI - Carrier-mediated GABA release activates GABA receptors on hippocampal neurons.
AB - gamma-Aminobutyric acid (GABA) transporters are electrogenic and sodium-dependent
and can operate in reverse when cells are depolarized or when there is reversal
of the inward sodium gradient. However, the functional relevance of this
phenomenon is unclear. We have examined whether depolarization induced by a
physiologically relevant increase in extracellular [K+] leads to sufficient
amounts of carrier-mediated GABA release to activate GABAA receptors on neurons.
Patch-clamp recordings were made from rat hippocampal neurons in culture with
solutions designed to isolate chloride currents in the recorded neuron. Pressure
microejection was used to increase extracellular [K+] from 3 to 12 mM. After
blockade of vesicular GABA release by removal of extracellular calcium, this
stimulus induced a large conductance increase in hippocampal neurons [18.9 +/-
6.8 (SD) nS; n = 16]. This was blocked by the GABAA receptor antagonists
picrotoxin and bicuculline and had a reversal potential that followed the Nernst
potential for chloride, indicating that it was mediated by GABAA receptor
activation. Similar responses occurred after block of vesicular neurotransmitter
release by tetanus toxin. GABAA receptors also were activated when an increase in
extracellular [K+] (from 3 to 13 mM) was combined with a reduction in
extracellular [Na+] or when cells were exposed to a decrease in extracellular
[Na+] alone. These results indicate that depolarization and/or reversal of the
Na+ gradient activated GABA receptors via release of GABA from neighboring cells.
We found that the GABA transporter antagonists 1-(4, 4-diphenyl-3-butenyl)-3
piperidinecarboxylic acid hydrochloride (SKF89976A; 20-100 microM) and 1-(2
([(diphenylmethylene)amino]oxy)ethyl) -1, 2, 5, 6 - tetrahydro - 3 - pyridine -
carboxylic acid hydrochloride (NO-711; 10 microM) both decreased the responses,
indicating that the release of GABA resulted from reversal of the GABA
transporter. We propose that carrier-mediated GABA release occurs in vivo during
high-frequency neuronal firing and seizures, and dynamically modulates inhibitory
tone.
PMID- 9658051
TI - Distinct GABAB actions via synaptic and extrasynaptic receptors in rat
hippocampus in vitro.
AB - Intracellular recordings were obtained from pyramidal cells to examine gamma
aminobutyric acid-B (GABAB)-mediated synaptic mechanisms in the CA1 region of rat
hippocampal slices. To investigate if heterogeneous ionic mechanisms linked to
GABAB receptors originate from distinct sets of inhibitory fibers, GABAB-mediated
monosynaptic late inhibitory postsynaptic potentials (IPSPs) were elicited in the
presence of antagonists of ionotropic glutamate and GABAA receptors and of an
inhibitor of GABA uptake and were compared after direct stimulation of inhibitory
fibers in three different CA1 layers: stratum oriens, radiatum, and lacunosum
moleculare. No significant differences were found in mean amplitude, rise time,
or time to decay to half-amplitude of IPSPs evoked from the three layers. Mean
equilibrium potential (Erev) of late IPSPs was similar for all groups and close
to the equilibrium potential of K+. Bath application of the GABAB antagonist
CGP55845A blocked all monosynaptic late IPSPs. During recordings with
micropipettes containing guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS), the
mean amplitude of all GABAB IPSPs gradually was reduced. Bath application of Ba2+
completely eliminated monosynaptic late IPSPs evoked from any of the stimulation
sites. Late IPSPs were blocked completely during Ba2+ applications that reduced
the GABAB-mediated hyperpolarizations elicited by local application of exogenous
GABA only by approximately 50%. These results indicate that heterogenous K+
conductances activated by GABAB receptors do not originate from separate sets of
inhibitory fibers in these layers. To examine if synchronous release of GABA from
a larger number of inhibitory fibers could activate heterogeneous GABAB
mechanisms, giant GABAB IPSPs were induced by 4-aminopyridine (4-AP) in the
presence of antagonists of ionotropic glutamate and GABAA receptors. The
amplitude and time course 4-AP-induced late IPSPs were approximately double that
of evoked monosynaptic late IPSPs, but their voltage sensitivity, Erev, and
antagonism by the GABAB antagonist CGP55845A and intracellular GTPgammaS were
similar. Ba2+ completely abolished 4-AP-induced late IPSPs, whereas responses
elicited by exogenous GABA were only reduced by approximately 50% in the same
cells. These results indicate that synchronous activation of large numbers of
inhibitory fibers, as induced by 4-AP, may not activate heterogenous GABAB
mediated conductances. Similarly, Ba2+ almost completely blocked late inhibitory
postsynaptic currents evoked by stimulus trains. Overall, our results show that
exogenous GABA can activate heterogenous K+ conductances via GABAB receptors, but
that GABA released synaptically, either by electrical stimulation or 4-AP
application, can only activate K+ conductances homogeneously sensitive to Ba2+.
Thus GABAB receptors located at synaptic and extrasynaptic sites on hippocampal
pyramidal cells may be linked to distinct K+ conductances.
PMID- 9658052
TI - Decorrelating actions of Renshaw interneurons on the firing of spinal motoneurons
within a motor nucleus: a simulation study.
AB - A simulation of spinal motoneurons and Renshaw cells was constructed to examine
possible functions of recurrent inhibition. Recurrent inhibitory feedback via
Renshaw cells is known to be weak. In our model, consistent with this, motoneuron
firing was only reduced by a few pulses per second. Our initial hypothesis was
that Renshaw cells would suppress synchronous firings of motoneurons caused by
shared, dynamic inputs. Each motoneuron received an identical pattern of noise in
its input. Synchrony coefficients were defined as the average motoneuron
population firing relative to the activity of selected reference motoneurons;
positive coefficients resulted if the motoneuron population was particularly
active at the same time the reference motoneuron was active. With or without
recurrent inhibition, the motoneuron pools tended to show little if any
synchronization. Recurrent inhibition was expected to reduce the synchrony even
further. Instead, it reduced the variance of the synchrony coefficients, without
a comparable effect on the average. This suggests-surprisingly-that both positive
and negative correlations between motoneurons are suppressed by recurrent
inhibition. In short, recurrent inhibition may operate as a negative feedback
mechanism to decorrelate motoneurons linked by common inputs. A consequence of
this decorrelation is the suppression of spectral activity that apparently arises
from correlated motoneuron firings due to common excitatory drive. Without
recurrent inhibition, the power spectrum of the total motoneuron pool firings
showed a peak at a frequency corresponding to the largest measured firing rates
of motoneurons in the pool. Recurrent inhibition either reduced or abolished this
peak, presumably by minimizing the likelihood of correlated firing among pool
elements. Renshaw cells may act to diminish physiological tremor, by removing
oscillatory components from aggregate motoneuron activity. Recurrent inhibition
also improved coherence between the aggregate motoneuron output and the common
drive, at frequencies above the frequency of the "synchronous" peak. Sensitivity
analyses demonstrated that the spectral effect became stronger as the duration of
inhibitory synaptic conductance was shortened with either the magnitude or the
spatial extent of the inhibitory conductances increased to maintain constant net
inhibition. Overall, Renshaw inhibition appears to be a powerful way to adjust
the dynamic behavior of a neuron population with minimal impact on its static
gain.
PMID- 9658053
TI - Effects of shape-discrimination training on the selectivity of inferotemporal
cells in adult monkeys.
AB - Through extensive training, humans can become "visual experts, " able to visually
distinguish subtle differences among similar objects with greater ease than those
who are untrained. To understand the neural mechanisms behind this acquired
discrimination ability, adult monkeys were fully trained to discriminate 28
moderately complex shapes. The training effects on the stimulus selectivity of
cells in area TE of the inferotemporal cortex were then examined in anesthetized
preparations. Area TE represents a later stage of the ventral visual cortical
pathway that is known to mediate visual object discrimination and recognition.
The recordings from the trained monkeys and untrained controls showed that the
proportion of TE cells responsive to some member of the 28 stimuli was
significantly greater in the trained monkeys than that in the control monkeys.
Cell responses recorded from the trained monkeys were not sharply tuned to single
training stimuli, but rather broadly covered several training stimuli. The
distances among the training stimuli in the response space spanned by responses
of the recorded TE cells were significantly greater in the trained monkeys than
those in the control monkeys. The subset of training stimuli to which individual
cells responded differed from cell to cell with only partial overlaps, suggesting
that the cells responded to features common to several stimuli. These results are
consistent with a model in which visual expertise is acquired through the
development of differential responses by inferotemporal cells to the images of
relevant objects.
PMID- 9658054
TI - Physiological properties of neurons in the optic layer of the rat's superior
colliculus.
AB - We made intracellular recordings from 74 neurons in the optic layer of the rat
superior colliculus (SC). Resting membrane potentials were -62.3 +/- 6.2 (SD) mV,
and input resistances were 37.9 +/- 10.1 MOmega. Optic layer neurons had large
sodium spikes (74.2 +/- 12.3 mV) with an overshoot of 12 mV and a half-amplitude
duration of 0.75 +/- 0.2 ms. Each sodium spike was followed by two
afterhyperpolarizations (AHPs), one of short duration and one of longer duration,
which were mediated by tetraethylammonium (TEA)-sensitive (IC) or apamin
sensitive (IAHP) calcium-activated potassium currents, respectively. Sodium
spikes were also followed by an afterdepolarization (ADP), which was only
revealed when the AHPs were blocked by TEA or apamin. In response to
hyperpolarizing current pulses, optic layer neurons showed an inward
rectification mediated by H channels. At the break of the current pulse, there
was a rebound low-threshold spike (LTS) with a short duration of <25 ms. The LTS
usually induced two sodium spikes (doublet). Most optic layer neurons (84%)
behaved as intrinsically bursting cells. They responded to suprathreshold
depolarization with an initial burst (or doublet) followed by a train of regular
single spikes. The remaining 16% of cells acted as chattering cells with high
frequency gamma (20-80 Hz) rhythmic burst firing within a narrow range of
depolarized potentials. The interburst frequency was voltage dependent and also
time dependent, i.e., showed frequency adaptation. Unmasking the ADP with either
TEA or apamin converted all of the tested intrinsically bursting cells into
chattering cells, indicating that the ADP played a crucial role in the generation
of rhythmic burst firing. Optic layer neurons receive direct retinal excitation
mediated by both N-methyl--aspartate (NMDA) and non-NMDA receptors. Optic tract
(OT) stimulation also led to gamma-aminobutyric acid-A (GABAA) receptor-mediated
inhibition, the main effect of which was to curtail the excitatory response to
retinal inputs by shunting the excitatory postsynaptic current. Intracellular
staining with biocytin showed that the optic layer neurons that we recorded from
were mostly either wide-field vertical neurons or other cells with predominately
superficially projecting dendrites. These cells were similar to calbindin
immunoreactive cells seen in the optic layer. The characteristics of these optic
layer neurons, such as prominent AHPs, strong shunting effect of inhibition, and
short-lasting LTS, suggest that they respond transiently to retinal inputs. This
is consistent with a function for these cells as the first relay station in the
extrageniculate visual pathway.
PMID- 9658055
TI - Inhibitory synapses among interneurons in the glomerular layer of rat and frog
olfactory bulbs.
AB - The patch-clamp technique was applied to periglomerular (PG) cells from slices of
frog and rat olfactory bulbs to characterize whole cell and single-channel
properties of inhibitory synaptic currents. Spontaneous and electrically driven
bicuculline-sensitive synaptic events were recorded under ionic conditions that
excluded any possible interference of excitatory synapses. The peak amplitude
distribution of spontaneous events could be fitted by several Gaussians having
the same interpeak distance. Spontaneous currents reversed polarity at the
chloride equilibrium potential and were suppressed by 2 mM Co2+; the decay phase
could be fitted with a single exponential having a time constant of approximately
10 ms at 0 mV. Bicuculline-sensitive monosynaptic responses could be evoked in PG
cells by electrical stimulations delivered at the distance of several glomeruli
within the glomerular layer. Finally, in excised outside-out patches, single
channel analysis revealed the presence of typical gamma-aminobutyric acid-A
receptor channels, with a single-channel conductance of 28 pS in symmetrical
chloride and mean open times of 3-4 ms. The simplest explanation of these data,
effectively supported by pristine anatomic findings, is that there could be
inhibitory contacts among interneurons in the glomerular layer.
PMID- 9658056
TI - Increased calcium buffering in basal forebrain neurons during aging.
AB - Increased calcium buffering in basal forebrain neurons during aging. J.
Neurophysiol. 80: 350-364, 1998. Alterations of neuronal calcium (Ca2+)
homeostasis are thought to underlie many age-related changes in the nervous
system. Basal forebrain neurons are susceptible to changes associated with aging
and to related dysfunctions such as Alzheimer's disease. It recently was shown
that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of
aged (24-27 mo) F344 rats have an increased current influx through voltage-gated
Ca2+ channels (VGCCs) relative to those of young (1-4. 5 mo) rats. Possible age
related changes in Ca2+ buffering in these neurons have been investigated using
conventional whole cell and perforated-patch voltage clamp combined with fura-2
microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i),
Ca2+ influx, Ca2+ transients (Delta[Ca2+]i), and time course of Delta[Ca2+]i were
quantitated, and rapid Ca2+ buffering values were calculated in MS/nDB neurons
from young and aged rats. The involvement of the smooth endoplasmic reticulum
(SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related
increase in rapid Ca2+ buffering and Delta[Ca2+]i time course was observed,
although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible
buffering mechanisms were found to have roles in Ca2+ buffering, but they did not
mediate the age-related changes. These findings suggest a model in which some
aging central neurons could compensate for increased Ca2+ influx with greater
Ca2+ buffering.
PMID- 9658057
TI - Spontaneous electromyographic activity in adult rat soleus muscle.
AB - Single-motor-unit and gross electromyograms (EMG) were recorded from the soleus
muscle in six unrestrained rats. The median firing frequencies of nine motor
units were in the 16-25 Hz range, in agreement with previous studies. One
additional motor unit had a median firing frequency of 47 Hz. This unit and one
of the lower-frequency units regularly fired doublets. Motor-unit firing
frequency was well correlated to whole-muscle EMG during locomotion. Integrated
rectified gross EMG revealed periods of continuous modulation, phasic high
amplitude events, and tonic low-amplitude segments. The tonic segments typically
were caused by a small number of motor units firing at stable high frequencies
(20-30 Hz) for extended periods of time without detectable activity in other
units. This long-lasting firing in single motor units typically was initiated by
transient mass activity, which recruited many units. However, only one or a few
units continued firing at a stable high frequency. The tonic firing terminated
spontaneously or in conjunction with an episode of mass activity. Different units
were active in different tonic segments. Thus there was an apparent dissociation
between activity in different single motor units and consequently between single
motor-unit activity and whole-muscle EMG. It is proposed that the maintained
tonic motor-unit activity is caused by intrinsic motoneuron properties in the
form of depolarizing plateau potentials.
PMID- 9658058
TI - Multiple second-messenger system modulation of voltage-activated calcium currents
in teleost retinal horizontal cells.
AB - Two voltage-activated calcium currents, a transient T-type and a PL-sustained
type, have been measured in isolated, cultured white bass horizontal cells. These
two voltage-activated calcium currents were found to be modulated by two
independent second-messenger systems. Furthermore, activation of either second
messenger system led to similar changes in calcium current activity. Activation
of the cyclic AMP second-messenger pathway or the sn-1,2-diacylglycerol (DAG)
second-messenger system resulted in a significant decrease in the amplitude of
the transient current and a simultaneous large increase in the amplitude of the
sustained current. Both second-messenger systems achieved their effects through
protein phosphorylation. The cyclic AMP pathway resulted in the activation of
protein kinase A (PKA) and the DAG pathway worked to activate protein kinase C
(PKC). Two protein kinase inhibitors were analyzed in this study for their
ability to inhibit second-messenger activated protein kinase activity and
separate the two pathways. The peptide cyclic AMP-dependent protein kinase
inhibitor and staurosporine were found to be nonspecific at high concentrations
and inhibited both second-messenger pathways. At low concentrations however,
staurosporine specifically inhibited only PKC, whereas adenosine 3',5'-cyclic
monophosphate (cAMP)-dependent protein kinase inhibitor was selective for PKA.
Both second-messenger systems were activated by the neuromodulator, dopamine.
Thus one agonist can initiate multiple second-messenger systems leading to
similar changes in voltage-activated calcium current activity. The modulatory
action on calcium currents produced by one second-messenger system added to the
modulatory action resulting from activation of the other second-messenger system.
The effect is to alter the magnitude of the horizontal cell calcium currents.
PMID- 9658059
TI - Corticoreticular pathways in the cat. I. Projection patterns and collaterization.
AB - This paper summarizes and compares the projection patterns and the receptive
fields of cortical neurons in areas 4 and 6 that project to the pontomedullary
reticular formation (PMRF). A total of 326 neurons were recorded in area 4 and
129 in area 6 in four awake, unrestrained cats that were chronically implanted
with arrays of electrodes in the PMRF and the pyramidal tract (PT). In area 4,
47% of the neurons projected to the caudal PT but not to the PMRF (PTNs); 19%
were activated only from the PMRF [corticoreticular neurons (CRNs)], whereas 27%
were activated from both the PT and the PMRF (PTN/CRNs). More PTN/CRNs conducted
at velocities >20 m/s (82%) than did CRNs (23%). In area 6, only 19% of the
neurons were identified as PTNs, 12% were PTN/CRNs and 31% were CRNs; a further
38% could not be activated from either structure. Collateral branches within the
PMRF conducted at maximum velocities of 20 m/s (average = 6.5 m/s). No
significant differences in the conduction velocities of the collateral branches
were found either between fast and slow PTNs or between area 4 and area 6
neurons. A large proportion of neurons in area 4 (85/173, 49%) were activated by
passive manipulation of the more distal, contralateral forelimb, with
approximately equal numbers being classed as PTNs, PTN/CRNs and CRNs. Most
neurons in area 6 for which a receptive field could be found were excited by
lightly touching or tapping the face and neck; a receptive field could not be
determined for 39% of the area 6 neurons compared with only 5% of those in area
4. Finally, there was evidence that neurons in quite widespread areas of the
pericruciate cortex, including both areas 4 and 6 projected onto similar,
restricted regions of the PMRF. The fact that the cortical projection from area 4
to the PMRF includes a high percentage of fast PTNs with a receptive field on the
distal forelimb is consistent with the view that this projection may serve to
integrate movement and the dynamic postural adjustments that accompany them. The
fact that the cortical projection from area 6 to the PMRF is primarily from slow
PTNs with receptive fields on the face, neck and back is consistent with a role
for this cortical area in adjusting the general posture of the animal on which
movements are superimposed.
PMID- 9658060
TI - Corticoreticular pathways in the cat. II. Discharge activity of neurons in area 4
during voluntary gait modifications.
AB - We propose that the descending command from area 4 that is responsible, in part,
for the change in limb trajectory required to step over an obstacle in one's path
also plays a role in triggering the anticipatory postural modifications that
accompany this movement. To test this hypothesis, we recorded the discharge
characteristics of identified classes of corticofugal neurons in area 4 of the
cat. Neurons were identified either as: pryamidal tract neurons (PTNs) if their
axon projected to the caudal pyramidal tract (PT) but not to the pontomedullary
reticular formation (PMRF); as corticoreticular neurons (CRNs) if their axon
projected to the PMRF but not to the PT; and as PTN/CRNs if their axon projected
to both structures. Altogether, the discharge properties of 212 corticofugal
neurons (109 PTNs, 66 PTN/CRNs, and 37 CRNs) within area 4 were recorded during
voluntary gait modifications. Neurons in all three classes showed increases in
their discharge frequency during locomotion and included groups that increased
their discharge either during the swing phase of the modified step, during the
subsequent stance phase, or in the stance phase of the cycle preceding the step
over the obstacle. A slightly higher percentage of CRNs (39%) discharged in the
stance phase prior to the gait modification than did the PTNs or PTN/CRNs (20%
and 17% respectively). In 37 electrode penetrations, we were able to record
clusters of 3 or more neurons within 500 micro(m) of each other. In most cases,
PTN/CRNs recorded in close proximity to PTNs had similar receptive fields and
discharged in a similar, but not identical, manner during the gait modifications.
Compared with adjacent PTNs, CRNs normally showed a more variable pattern of
activity and frequently discharged earlier in the step cycle than did the PTNs or
PTN/CRNs. We interpret the results as providing support for the original
hypothesis. We suggest that the collateral branches to the PMRF from corticofugal
neurons with axons that continue at least as far as the caudal PT provide a
signal that could be used to trigger dynamic postural responses that are
appropriately organized and scaled for the movements that are being undertaken.
We suggest that the more variable and earlier discharge activity observed in CRNs
might be used to modify the postural support on which the movements and the
dynamic postural adjustments are superimposed.
PMID- 9658061
TI - Interactions between idiothetic cues and external landmarks in the control of
place cells and head direction cells.
AB - Two types of neurons in the rat brain have been proposed to participate in
spatial learning and navigation: place cells, which fire selectively in specific
locations of an environment and which may constitute key elements of cognitive
maps, and head direction cells, which fire selectively when the rat's head is
pointed in a specific direction and which may serve as an internal compass to
orient the cognitive map. The spatially and directionally selective properties of
these cells arise from a complex interaction between input from external
landmarks and from idiothetic cues; however, the exact nature of this interaction
is poorly understood. To address this issue, directional information from visual
landmarks was placed in direct conflict with directional information from
idiothetic cues. When the mismatch between the two sources of information was
small (45 degrees), the visual landmarks had robust control over the firing
properties of place cells; when the mismatch was larger, however, the firing
fields of the place cells were altered radically, and the hippocampus formed a
new representation of the environment. Similarly, the visual cues had control
over the firing properties of head direction cells when the mismatch was small
(45 degrees), but the idiothetic input usually predominated over the visual
landmarks when the mismatch was larger. Under some conditions, when the visual
landmarks predominated after a large mismatch, there was always a delay before
the visual cues exerted their control over head direction cells. These results
support recent models proposing that prewired intrinsic connections enable
idiothetic cues to serve as the primary drive on place cells and head direction
cells, whereas modifiable extrinsic connections mediate a learned, secondary
influence of visual landmarks.
PMID- 9658062
TI - Spatiotemporal patterns at the retinal output.
AB - Edge enhancement in the retina is thought to be mediated by classical center
surround antagonism, first encountered as the interactions between horizontal
cells and cones. But in the salamander retina these interactions do little to
enhance edges. Instead, a robust dynamic interaction between amacrine and bipolar
cells appears to be responsible for a sharp edge enhancement. To demonstrate this
we recorded extracellularly from a single ganglion cell and moved a flashed
square, 300 micro(m) on a side, over a 1.5 x 1.0 mm2 grid at 25-micro(m)
increments. Playing back all of these recordings simultaneously simulated the
pattern of responses that would have been measured from an array of ganglion
cells. The emerging pattern of ganglion cell activity first faithfully
represented the flashed square, but after approximately 60 ms the center of the
representation collapsed, leaving a representation of only the edges. We inferred
that the feedback synapse from amacrine to bipolar cells at gamma-aminobutyric
acid-C (GABAC) receptors mediated this effect: bicuculline and strychnine were
ineffective in altering the response pattern, but in picrotoxin the center of the
representation did not collapse. The GABAergic amacrine cells thought to mediate
this effect have quite narrow spread of processes, so the existence of this edge
enhancing effect suggests a mechanism quite different from classical lateral
inhibition, namely the delayed inhibition of a spatially expanding input pattern.
PMID- 9658063
TI - Cell-permeable scavengers of superoxide prevent long-term potentiation in
hippocampal area CA1.
AB - Long-term potentiation (LTP) in hippocampal area CA1 is generally dependent on N
methyl--aspartate (NMDA) receptor activation. Reactive oxygen species (ROS),
including superoxide, are produced in response to NMDA receptor activation in a
number of brain regions, including the hipppocampus. In this study, two cell
permeable manganese porphyrin compounds that mimic superoxide dismutase (SOD)
were used to determine whether production of superoxide is required for the
induction of LTP in area CA1 of rat hippocampal slices. Incubation of hippocampal
slices with either Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or
Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP) prevented the induction
of LTP. Incubation of slices with either light-inactivated MnTBAP or light
inactivated MnTMPyP had no effect on induction of LTP. Neither MnTBAP nor MnTMPyP
was able to reverse preestablished LTP. These observations suggest that
production of superoxide occurs in response to LTP-inducing stimulation and that
superoxide is necessary for the induction of LTP.
PMID- 9658064
TI - Deficits in smooth-pursuit eye movements after muscimol inactivation within the
primate's frontal eye field.
AB - To evaluate smooth-pursuit (SP) function in the primate frontal eye field (FEF),
microinjections of muscimol, a gamma-aminobutyric acid (GABA) agonist, were used
to reversibly deactivate physiologically characterized sites in FEF. SP was
severely impaired by deactivation at sites in the FEF's smooth eye movement
region (FEFsem) located in the fundus and posterior bank of the macaque monkey's
arcuate sulcus. These SP deficits were apparent immediately after the muscimol
injection and persisted for several hours but recovered by the next day. SP was
most drastically and consistently impaired for directions similar to the injected
site's elicited smooth eye movement direction or to the optimal SP direction for
its neuronal responses. Targets moving in these directions, usually ipsilateral
to the injected hemisphere, were tracked primarily with saccades after the
muscimol injection, the peak SP velocity being only 10-30% of preinjection
velocity. SP in other directions, including contralateral, was less strongly
affected. Initial SP acceleration in response to target motion onset was also
significantly diminished, generally by approximately the same proportion as peak
SP velocity. In contrast, saccades were largely unaffected by muscimol injections
in FEFsem; nor was there an immediate effect on SP when control sites in the
saccadic region of FEF (FEFsac) were deactivated, although a SP deficit often
appeared 30-60 min after FEFsac injections, possibly reflecting diffusion of
muscimol into neighboring FEFsem. These reversible SP deficits produced by
muscimol inactivation within FEFsem are similar to permanent deficits caused by
large aspiration lesions of FEF and indicate that inclusion of FEFsem is the
critical factor determining whether FEF lesions impair SP. The severity of the
reversible deficits found here indicates how extremely critical FEFsem is for
normal highgain SP.
PMID- 9658065
TI - Role of the Fas/Fas ligand apoptotic pathway in human immunodeficiency virus type
1 disease.
PMID- 9658066
TI - Attenuation of influenza A virus mRNA levels by promoter mutations.
AB - We have engineered influenza A/WSN/33 viruses which have viral RNA (vRNA)
segments with altered base pairs in the conserved double-stranded region of their
vRNA promoters. The mutations were introduced into the segment coding for the
neuraminidase (NA) by using a reverse genetics system. Two of the rescued viruses
which share a C-G-->A-U double mutation at positions 11 and 12' at the 3' and 5'
ends of the NA-specific vRNA, respectively, showed approximately a 10-fold
reduction of NA levels. The mutations did not dramatically affect the NA-specific
vRNA levels found in virions or the NA-specific vRNA and cRNA levels in infected
cells. In contrast, there was a significant decrease in the steady-state levels
of NA-specific mRNAs in infected cells. Transcription studies in vitro with
ribonucleoprotein complexes isolated from the two transfectant viruses indicated
that transcription initiation of the NA-specific segment was not affected.
However, the majority of NA-specific transcripts lacked poly(A) tails, suggesting
that mutations in the double-stranded region of the influenza virus vRNA promoter
can attenuate polyadenylation of mRNA molecules. This is the first time that a
promoter mutation in an engineered influenza virus has shown a differential
effect on influenza virus RNA transcription and replication.
PMID- 9658067
TI - The herpesvirus transactivator VP16 mimics a human basic domain leucine zipper
protein, luman, in its interaction with HCF.
AB - In human cells infected with herpes simplex virus (HSV), viral gene expression is
initiated by the virion protein VP16. VP16 does not bind DNA directly but forms a
multiprotein complex on the viral immediate-early gene promoters with two
cellular proteins: the POU domain protein Oct-1 and host cell factor (HCF; also
called C1, VCAF, and CFF). Despite its apparent role in stabilizing the VP16
induced transcription complex, the natural biological role of HCF is unclear.
Only recently HCF has been implicated in control of the cell cycle. To determine
the role of HCF in cells and answer why HSV has evolved an HCF-dependent
mechanism for the initiation of the lytic cycle, we identified the first human
ligand for HCF (R. Lu et al., Mol. Cell. Biol. 17:5117-5126, 1997). This protein,
Luman, is a member of the CREB/ATF family of transcription factors that can
activate transcription from promoters containing cyclic AMP response elements
(CRE). Here we provide evidence that Luman and VP16 share two important
structural features: an acidic activation domain and a common mechanism for
binding HCF. We found that Luman, its homolog in Drosophila, dCREB-A (also known
as BBF-2), and VP16 bind to HCF by a motif, (D/E)HXY(S/A), present in all three
proteins. In addition, a mutation (P134S) in HCF that prevents VP16 binding also
abolishes its binding to Luman and dCREB-A. We also show that while interaction
with HCF is not required for the ability of Luman to activate transcription when
tethered to the GAL4 promoter, it appears to be essential for Luman to activate
transcription through CRE sites. These data suggest that the HCF-Luman
interaction may represent a conserved mechanism for transcriptional regulation in
metazoans, and HSV mimics this interaction with HCF to monitor the physiological
state of the host cell.
PMID- 9658068
TI - A subset of porcine reproductive and respiratory syndrome virus GP3 glycoprotein
is released into the culture medium of cells as a non-virion-associated and
membrane-free (soluble) form.
AB - The GP3 protein of the IAF-Klop strain of porcine reproductive and respiratory
syndrome virus (PRRSV) was expressed in 293 cells by a recombinant human type 5
adenovirus carrying the open reading frame 3 gene. The protein exhibited a
molecular mass of 42 kDa and comigrated with GP3 expressed in PRRSV-infected MARC
145 cells. Removal of N-linked glycans from GP3 resulted in a 27-kDa protein
(P3), confirming its highly glycosylated nature. Pulse-chase experiments carried
out either in the context of PRRSV infection or upon individual expression of GP3
in 293 cells showed that the protein remains completely endo-beta-N
acetylglucosaminidase H-sensitive even after 4 h of synthesis. Thus, the
transport of GP3 was restricted to the premedial Golgi compartment, presumably
the endoplasmic reticulum (ER). However, a minor fraction of GP3 was found to be
secreted in the culture medium as a soluble membrane-free form. This released
protein (sGP3) was readily identified upon individual expression of GP3 in 293
cells as well as in the context of PRRSV infection, albeit at lower levels. The
sGP3 migrated as a smear and displayed a molecular mass ranging from 43 to 53
kDa. The unglycosylated form of sGP3 comigrated with its intracellular
deglycosylated counterpart, suggesting that the release from the cell of a subset
of GP3 did not result from cleavage of a putative membrane-anchor sequence.
Strikingly, unlike GP3, the sGP3 acquired Golgi-specific modifications of its
carbohydrate side chains and folded into a disulfide-linked homodimer. Brefeldin
A treatment completely abolished the release of sGP3, suggesting that the ER-to
Golgi compartment is an obligatory step in cellular secretion of sGP3. In
contrast, 10 mM monensin did not prevent sGP3 release but inhibited the terminal
glycosylation that confers on the protein its diffuse pattern. Since GP3 was
found to be nonstructural in the case of the North American strain, secretion of
a minor fraction of GP3 might be an explanation for its high degree of
immunogenicity in infected pigs. Furthermore, this secreted protein might be
relevant as a model for further studies on the cellular subcompartments involved
in the sorting of proteins to the extracellular milieu.
PMID- 9658069
TI - Characterization of a cis-acting sequence in the Pol region required to transfer
human foamy virus vectors.
AB - To identify cis-acting elements in the foamy virus (FV) RNA pregenome, we
developed a transient-vector-production system based on cotransfection of
indicator gene-bearing vector and gag-pol and env expression plasmids. Two
elements which were critical for vector transfer were found and mapped
approximately. The first element was located in the RU5 leader and the 5' gag
region (approximately up to position 650 of the viral RNA). The second element
was located in an approximately 2-kb sequence in the 3' pol region. Although
small 5' and 3' deletions, as well as internal deletions of the latter element,
were tolerated, both elements were found to be absolutely required for vector
transfer. The functional characterization of the pol region-located cis-acting
element revealed that it is essential for efficient incorporation or the
stability of particle-associated virion RNA. Furthermore, virions derived from a
vector lacking this sequence were found to be deficient in the cleavage of the
Gag protein by the Pol precursor protease. Our results suggest that during the
formation of infectious virions, complex interactions between FV Gag and Pol and
the viral RNA take place.
PMID- 9658070
TI - Inhibition of simian immunodeficiency virus (SIV) replication by CD8(+) T
lymphocytes from macaques immunized with live attenuated SIV.
AB - Characterization of immune responses induced by live attenuated simian
immunodeficiency virus (SIV) strains may yield clues to the nature of protective
immunity induced by this vaccine approach. We investigated the ability of CD8(+)
T lymphocytes from rhesus macaques immunized with the live, attenuated SIV strain
SIVmac239Deltanef or SIVmac239Delta3 to inhibit SIV replication. CD8(+) T
lymphocytes from immunized animals were able to potently suppress SIV replication
in autologous SIV-infected CD4(+) T cells. Suppression of SIV replication by
unstimulated CD8(+) T cells required direct contact and was major
histocompatibility complex (MHC) restricted. However, CD3-stimulated CD8(+) T
cells produced soluble factors that inhibited SIV replication in an MHC
unrestricted fashion as much as 30-fold. Supernatants from stimulated CD8(+) T
cells were also able to inhibit replication of both CCR5- and CXCR4-dependent
human immunodeficiency virus type 1 (HIV-1) strains. Stimulation of CD8(+) cells
with cognate cytotoxic T-lymphocyte epitopes also induced secretion of soluble
factors able to inhibit SIV replication. Production of RANTES, macrophage
inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T
cells of vaccinated animals was almost 10-fold higher than that from stimulated
CD8(+) T cells of control animals. However, addition of antibodies that
neutralize these beta-chemokines, either alone or in combination, only partly
blocked inhibition of SIV and HIV replication by soluble factors produced by
stimulated CD8(+) T cells. Our results indicate that inhibition of SIV
replication by CD8(+) T cells from animals immunized with live attenuated SIV
strains involves both MHC-restricted and -unrestricted mechanisms and that MHC
unrestricted inhibition of SIV replication is due principally to soluble factors
other than RANTES, MIP-1alpha, and MIP-1beta.
PMID- 9658071
TI - Mouse adenovirus type 1 early region 1A is dispensable for growth in cultured
fibroblasts.
AB - Mouse adenovirus type 1 (MAV-1) mutants with deletions of conserved regions of
early region 1A (E1A) or with point mutations that eliminate translation of E1A
were used to determine the role of E1A in MAV-1 replication. MAV-1 E1A mutants
expressing no E1A protein grew to titers comparable to wild-type MAV-1 titers on
mouse fibroblasts (3T6 fibroblasts and fibroblasts derived from Rb+/+, Rb+/-, and
Rb-/- transgenic embryos). To test the hypothesis that E1A could induce a
quiescent cell to reenter the cell cycle, fibroblasts were serum starved to stop
DNA replication and cellular replication and then infected with the E1A mutant
and wild-type viruses. All grew to equivalent titers. Steady-state levels of MAV
1 early mRNAs (E1A, E1B, E2, E3, and E4) from 3T6 cells infected with wild-type
or E1A mutant virus were examined by Northern analysis. Steady-state levels of
mRNAs from the mutant-infected cells were comparable to or greater than the
levels found in wild-type virus infections for most of the early regions and for
two late genes. The E2 mRNA levels were slightly reduced in all mutant infections
relative to wild-type infections. E1A mRNA was not detected from infections with
the MAV-1 E1A null mutant, pmE109, or from infections with similar MAV-1 E1A null
mutants, pmE112 and pmE113. The implications for the lack of a requirement of E1A
in cell culture are discussed.
PMID- 9658072
TI - Determinants of human immunodeficiency virus type 1 envelope glycoprotein
activation by soluble CD4 and monoclonal antibodies.
AB - Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is
enhanced by the binding of subneutralizing concentrations of soluble receptor,
soluble CD4 (sCD4), or monoclonal antibodies directed against the viral envelope
glycoproteins. In this work, we studied the abilities of different antibodies to
mediate activation of the envelope glycoproteins of a primary HIV-1 isolate, YU2,
and identified the regions of gp120 envelope glycoprotein contributing to
activation. Binding of antibodies to a variety of epitopes on gp120, including
the CD4 binding site, the third variable (V3) loop, and CD4-induced epitopes,
enhanced the entry of viruses containing YU2 envelope glycoproteins. Fab
fragments of antibodies directed against either the CD4 binding site or V3 loop
also activated YU2 virus infection. The activation phenotype was conferred on the
envelope glycoproteins of a laboratory-adapted HIV-1 isolate (HXBc2) by replacing
the gp120 V3 loop or V1/V2 and V3 loops with those of the YU2 virus. Infection by
the YU2 virus in the presence of activating antibodies remained inhibitable by
macrophage inhibitory protein 1beta, indicating dependence on the CCR5 coreceptor
on the target cells. Thus, antibody enhancement of YU2 entry involves neither Fc
receptor binding nor envelope glycoprotein cross-linking, is determined by the
same variable loops that dictate enhancement by sCD4, and probably proceeds by a
process fundamentally similar to the receptor-activated virus entry pathway.
PMID- 9658073
TI - Cellular components interact with adenovirus type 5 minimal DNA packaging
domains.
AB - Adenovirus type 5 DNA packaging is initiated from the left end of the viral
genome and depends on the presence of a cis-acting packaging domain located
between nucleotides 194 and 380. Multiple redundant packaging elements (termed A
repeats I through VII [AI through AVII]) are contained within this domain and
display differential abilities to support DNA packaging in vivo. The functionally
most important repeats, AI, AII, AV, and AVI, follow a bipartite consensus motif
exhibiting AT-rich and CG-rich core sequences. Results from previous mutational
analyses defined a fragment containing AV, AVI, and AVII as a minimal packaging
domain in vivo, which supports a functional independence of the respective cis
acting sequences. Here we describe multimeric versions of individual packaging
elements as minimal packaging domains that can confer viability and packaging
activity to viruses carrying gross truncations within their left end. These
mutant viruses directly rate the functional role that different packaging
elements play relative to each other. The A repeats are likely to be binding
sites for limiting, trans-acting packaging factors of cellular and/or viral
origin. We report here the characterization of two cellular binding activities
interacting with all of the minimal packaging domains in vitro, an unknown
binding activity termed P-complex, and the transcription factor chicken ovalbumin
upstream promoter transcription factor. The binding of both activities is
dependent on the integrity of the AT-rich, but not the CG-rich, consensus half
site. In the case of P-complex, binding affinity for different minimal packaging
domains in vitro correlates well with their abilities to support DNA packaging in
vivo. Interestingly, P-complex interacts not only with packaging elements but
also with the left terminus of the viral genome, the core origin of replication.
Our data implicate cellular factors as components of the viral packaging
machinery. The dual binding specificity of P-complex for packaging and
replication sequences may further suggest a direct involvement of left-end
replication sequences in viral DNA encapsidation.
PMID- 9658074
TI - Phosphorylation of p53: a novel pathway for p53 inactivation in human T-cell
lymphotropic virus type 1-transformed cells.
AB - Inhibition of p53 function, through either mutation or interaction with viral or
cellular transforming proteins, correlates strongly with the oncogenic potential.
Only a small percentage of human T-cell lymphotropic virus type 1 (HTLV-1)
transformed cells carry p53 mutations, and mutated p53 genes have been found in
only one-fourth of adult T-cell leukemia cases. In previous studies, we
demonstrated that wild-type p53 is stabilized and transcriptionally inactive in
HTLV-1-transformed cells. Further, the viral transcriptional activator Tax plays
a role in both the stabilization and inactivation of p53 through a mechanism
involving the first 52 amino acids of p53. Here we show for the first time that
phosphorylation of p53 inactivates p53 by blocking its interaction with basal
transcription factors. Using two-dimensional peptide mapping, we demonstrate that
peptides corresponding to amino acids 1 to 19 and 387 to 393 are
hyperphosphorylated in HTLV-1-transformed cells. Moreover, using antibodies
specific for phosphorylated Ser15 and Ser392, we demonstrate increased
phosphorylation of these amino acids. Since HTLV-1 p53 binds DNA in a sequence
specific manner but fails to interact with TFIID, we tested whether
phosphorylation of the N terminus of p53 affected p53-TFIID interaction. Using
biotinylated peptides, we show that phosphorylation of Ser15 alone inhibits p53
TFIID interaction. In contrast, phosphorylation at Ser15 and -37 restores TFIID
binding and blocks MDM2 binding. Our studies provide evidence that HTLV-1
utilizes the posttranslational modification of p53 in vivo to inactivate function
of the tumor suppressor protein.
PMID- 9658075
TI - In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an
infectious form by the addition of the vesicular stomatitis virus surrogate
envelope G protein.
AB - In the absence of envelope gene expression, retrovirus packaging cell lines
expressing Moloney murine leukemia virus (MLV) gag and pol genes produce large
amounts of noninfectious virus-like particles that contain reverse transcriptase,
processed Gag protein, and viral RNA (gag-pol RNA particles). We demonstrate that
these particles can be made infectious in an in vitro, cell-free system by the
addition of a surrogate envelope protein, the G spike glycoprotein of vesicular
stomatitis virus (VSV-G). The appearance of infectivity is accompanied by
physical association of the G protein with the immature, noninfectious virus
particles. Similarly, exposure in vitro of wild-type VSV-G to a fusion-defective
pseudotyped virus containing a mutant VSV-G markedly increases the infectivity of
the virus to titers similar to those of conventional VSV-G pseudotyped viruses.
Furthermore, similar treatment of an amphotropic murine leukemia virus
significantly allows infection of BHK cells not otherwise susceptible to
infection with native amphotropic virus. The partially cell-free virus maturation
system reported here should be useful for studies aimed at the preparation of
tissue-targeted retrovirus vectors and will also aid in studies of nucleocapsid
envelope interactions during budding and of virus assembly and virus-receptor
interactions during virus uptake into infected cells. It may also represent a
potentially useful step toward the eventual development of a completely cell-free
retrovirus assembly system.
PMID- 9658076
TI - Multiple virulence determinants of foot-and-mouth disease virus in cell culture.
AB - Hypervirulent variants of foot-and-mouth disease virus (FMDV) of serotype C arise
upon serial cytolytic or persistent infections in cell culture. A specific
mutation in the internal ribosome entry site of persistent FMDV was previously
associated with enhanced translation initiation activity that could contribute to
the hypervirulent phenotype for BHK-21 cells. Here we report that several
hypervirulent FMDV variants arising upon serial cytolytic passage show an
invariant internal ribosome entry site but have a number of mutations affecting
structural and nonstructural viral proteins. The construction of chimeric type O
type C infectious transcripts has allowed the mapping of a major determinant of
hypervirulence to the viral capsid. Tissue culture-adapted FMDV displayed
enhanced affinity for heparin, but binding to cell surface heparan sulfate
moieties was not required for expression of the hypervirulent phenotype in
Chinese hamster ovary (CHO) cells. Virulence was identical or even higher for
glycosaminoglycan-deficient CHO cells than for wild-type CHO cells. FMDV variants
with decreased affinity for heparin were selected from a high-binding parental
population and analyzed. Substitutions associated with decreased heparin binding
were located at positions 173 of capsid protein VP3 and 144 of capsid protein
VP1. These substitutions had a moderate effect on virulence for BHK-21 cells but
completely abrogated infection of CHO cells. The comparative results with several
FMDV isolates show that (i) increased affinity for heparin and alterations in
cell tropism may be mediated by a number of independent sites on the viral capsid
and (ii) the same capsid modifications may have different effects on different
cell types.
PMID- 9658077
TI - Molecular mechanisms of serum resistance of human influenza H3N2 virus and their
involvement in virus adaptation in a new host.
AB - H3N2 human influenza viruses that are resistant to horse, pig, or rabbit serum
possess unique amino acid mutations in their hemagglutinin (HA) protein. To
determine the molecular mechanisms of this resistance, we characterized the
receptor-binding properties of these mutants by measuring their affinity for
total serum protein inhibitors and for soluble receptor analogs. Pig serum
resistant variants displayed a markedly decreased affinity for total pig serum
sialylglycoproteins (which contain predominantly 2-6 linkage between sialic acid
and galactose residues) and for the sialyloligosaccharide 6'-sialyl(N
acetyllactosamine). These properties correlated with the substitution 186S-->I in
HA1. The major inhibitory activity in rabbit serum was found to be a beta
inhibitor with characteristics of mannose-binding lectins. Rabbit serum-resistant
variants exhibited decreased sensitivity to this inhibitor due to the loss of a
glycosylation sequon at positions 246 to 248 of the HA. In addition to a somewhat
reduced affinity for 6'-sialyl(N-acetyllactosamine)-containing receptors, horse
serum-resistant variants lost the ability to bind the viral neuraminidase
resistant 4-O-acetylated sialic acid moieties of equine alpha2-macroglobulin
because of the mutation 145N-->K/D in their HA1. These results indicate that
influenza viruses become resistant to serum inhibitors because their affinity for
these inhibitors is reduced. To determine whether natural inhibitors play a role
in viral evolution during interspecies transmission, we compared the receptor
binding properties of H3N8 avian and equine viruses, including two strains
isolated during the 1989 to 1990 equine influenza outbreak, which was caused by
an avian virus in China. Avian strains bound 4-O-acetylated sialic acid residues
of equine alpha2-macroglobulin, whereas equine strains did not. The earliest
avian-like isolate from a horse influenza outbreak bound to this sialic acid with
an affinity similar to that of avian viruses; a later isolate, however, displayed
binding properties more similar to those of classical equine strains. These data
suggest that the neuraminidase-resistant sialylglycoconjugates present in horses
exert selective pressure on the receptor-binding properties of avian virus HA
after its introduction into this host.
PMID- 9658078
TI - Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to
the bicyclam AMD3100.
AB - The bicyclam AMD3100 is a potent and selective inhibitor of the replication of
human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2). It was recently
demonstrated that the compound inhibited HIV entry through CXCR4 but not through
CCR5. Selectivity of AMD3100 for CXCR4 was further indicated by its lack of
effect on HIV-1 and HIV-2 infection mediated by the CCR5, CCR3, Bonzo, BOB, and
US28, coreceptors. AMD3100 completely blocked HIV-1 infection mediated by a
mutant CXCR4 bearing a deletion of most of the amino-terminal extracellular
domain. In contrast, relative resistance to AMD3100 was conferred by different
single amino acid substitutions in the second extracellular loop (ECL2) or in the
adjacent membrane-spanning domain, TM4. Only substitutions of a neutral residue
for aspartic acid and of a nonaromatic residue for phenylalanine (Phe) were
associated with drug resistance. This suggests a direct interaction of AMD3100
with these amino acids rather than indirect effects of their mutation on the
CXCR4 structure. The interaction of aspartic acids of ECL2 and TM4 with AMD3100
is consistent with the positive charge of bicyclams, which might block HIV-1
entry by preventing electrostatic interactions between CXCR4 and the HIV-1
envelope protein gp120. Other features of AMD3100 must account for its high
antiviral activity, in particular the presence of an aromatic linker between the
cyclam units. This aromatic group might engage in hydrophobic interactions with
the Phe-X-Phe motifs of ECL2 or TM4. These results confirm the importance of ECL2
for the HIV coreceptor activity of CXCR4.
PMID- 9658079
TI - The cytomegalovirus-encoded chemokine receptor US28 can enhance cell-cell fusion
mediated by different viral proteins.
AB - The human cytomegalovirus (CMV) US28 gene encodes a functional CC chemokine
receptor. However, this activity was observed in cells transfected to express
US28 and might not correspond to the actual role of the protein in the CMV life
cycle. Expression of US28 allows human immunodeficiency virus type 1 (HIV-1)
entry into certain CD4(+) cells and their fusion with cells expressing HIV-1
envelope (Env) proteins. Such properties were initially reported for the cellular
chemokine receptors CCR5 and CXCR4, which behave as CD4-associated HIV-1
coreceptors. We found that coexpression of US28 and either CXCR4 or CCR5 in
CD4(+) cells resulted in enhanced synctium formation with HIV-1 Env+ cells. This
positive effect of US28 on cell fusion seems to be distinct from its HIV-1
coreceptor activity. Indeed, enhancement of cell fusion was also observed when
US28 was expressed on the HIV-1 Env+ cells instead of an CD4(+) target cells.
Furthermore, US28 could enhance cell fusion mediated by other viral proteins, in
particular, the G protein of vesicular stomatitis virus (VSV-G). The HIV-1
coreceptor and fusion-enhancing activities could be affected by mutations in
different domains of US28. The fusion-enhancing activity of US28 seems to be cell
type dependent. Indeed, cells coexpressing VSV-G and US28 fused more efficiently
with human, simian, or feline target cells, while US28 had no apparent effect on
fusion with the three mouse or rat cell lines tested. The positive effect of US28
on cell fusion might therefore require its interaction with a cell-specific
factor. We discuss a possible role for US28 in the fusion of the CMV envelope
with target cells and CMV entry.
PMID- 9658080
TI - Analysis of rotavirus nonstructural protein NSP5 phosphorylation.
AB - The rotavirus nonstructural phosphoprotein NSP5 is encoded by a gene in RNA
segment 11. Immunofluorescence analysis of fixed cells showed that NSP5
polypeptides remained confined to viroplasms even at a late stage when provirions
migrated from these structures. When NSP5 was expressed in COS-7 cells in the
absence of other viral proteins, it was uniformly distributed in the cytoplasm.
Under these conditions, the 26-kDa polypeptide predominated. In the presence of
the protein phosphatase inhibitor okadaic acid, the highly phosphorylated 28- and
32- to 35-kDa polypeptides were formed. Also, the fully phosphorylated protein
had a homogeneous cytoplasmic distribution in transfected cells. In rotavirus
SA11-infected cells, NSP5 synthesis was detectable at 2 h postinfection. However,
the newly formed 26-kDa NSP5 was not converted to the 28- to 35-kDa forms until
approximately 2 h later. Also, the protein kinase activity of isolated NSP5 was
not detectable until the 28- and 30- to 35-kDa NSP5 forms had been formed. NSP5
immunoprecipitated from extracts of transfected COS-7 cells was active in
autophosphorylation in vitro, demonstrating that other viral proteins were not
required for this function. Treatment of NSP5-expressing cells with
staurosporine, a broad-range protein kinase inhibitor, had only a limited
negative effect on the phosphorylation of the viral polypeptide. Staurosporine
did not inhibit autophosphorylation of NSP5 in vitro. Together, the data support
the idea that NSP5 has an autophosphorylation activity that is positively
regulated by addition of phosphate residues at some positions.
PMID- 9658082
TI - cis Elements required for high-level expression of unspliced Gag-containing
message in Moloney murine leukemia virus.
AB - The 441-nucleotide (nt) region (nt 5325 to 5766) around the splice acceptor (SA)
site (nt 5491) was found to be necessary for high-level expression of gag
containing unspliced RNA of Moloney murine leukemia virus (M. Oshima, T. Odawara,
T. Matano, H. Sakahira, K. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol.
70:2286-2295, 1996). Detailed genetic dissection of the 441-nt region revealed
that the 5'-end 64 nt (nt 5325 to 5389) were necessary for high-level expression
of the unspliced RNA when the spliced RNA was not produced, while the 3'-side 301
nt (nt 5466 to 5766) containing the SA site were necessary for producing spliced
RNA. When the spliced RNA was produced, the unspliced RNA could be expressed at a
high level even when the 5'-end 64 nt were absent. Probably the virus sequence
ensuring the splicing could produce an RNA structure able to compensate for the
function of the 5'-end 64-nt region responsible for the expression of the
unspliced RNA.
PMID- 9658081
TI - Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors
differentially regulates expression of inflammatory genes and activates the
MEK/ERK signaling pathway.
AB - We have previously shown that binding of human immunodeficiency virus type 1 (HIV
1) virions to CD4 receptors stimulates association of Lck with Raf-1 and results
in the activation of Raf-1 kinase in a Ras-independent manner. In the present
study, we demonstrate that HIV-1 envelope glycoproteins of both T-cell-tropic and
macrophagetropic strains rapidly activate the ERK/mitogen-activated protein (MAP)
kinase pathway and the binding of nuclear transcription factors (AP-1, NF-kappaB,
and C/EBP) and stimulate expression of cytokine and chemokine genes. The
activation of this signaling pathway requires functional CD4 receptors and is
independent of binding to CXCR4. Binding of the natural ligand stromal cell
derived factor 1 (SDF-1) to CXCR4, which inhibits entry of T-cell-tropic HIV-1,
activates also the ERK/MAP kinase pathway. However, SDF-1 did not affect the CD4
mediated expression of cytokine and chemokine genes. These results provide firm
molecular evidence that binding of HIV-1 envelope glycoproteins to CD4 receptor
initiates a signaling pathway(s) independent of the binding to the chemokine
receptor that leads to the aberrant expression of inflammatory genes and may
contribute significantly to HIV-1 replication as well as to deregulation of the
immune system.
PMID- 9658083
TI - Intestinal intraepithelial lymphocytes are primed for gamma interferon and MIP
1beta expression and display antiviral cytotoxic activity despite severe CD4(+) T
cell depletion in primary simian immunodeficiency virus infection.
AB - Intraepithelial lymphocytes (IEL) are a critical effector component of the gut
associated lymphoid tissue (GALT) and play an important role in mucosal immunity
as well as in the maintenance of the epithelial cell integrity and barrier
function. The objective of this study was to determine whether simian
immunodeficiency virus (SIV) infection of rhesus macaques would cause alterations
in the immunophenotypic profiles of IEL and their mitogen-specific cytokine
(gamma interferon [IFN-gamma] and MIP-1beta) responses (by flow cytometry) and
virus-specific cytotoxic T-cell (CTL) activity (by the chromium release assay).
Virally infected IEL were detected through the entire course of SIV infection by
in situ hybridization. Severe depletion of CD4(+) single-positive and
CD4(+)CD8(+) double-positive T cells occurred early in primary SIV infection,
which was coincident with an increased prevalence of CD8(+) T cells. This was in
contrast to a gradual depletion of CD4(+) T cells in peripheral blood. The CD8(+)
IEL were the primary producers of IFN-gamma and MIP-1beta and were found to
retain their potential to produce both IFN-gamma and MIP-1beta through the entire
course of SIV infection. SIV-specific CTL activity was detected in primary IEL at
1, 2, and 4 weeks post-SIV infection. These results demonstrated that IEL may be
involved in generating antiviral immune responses early in SIV infection and in
suppressing viral infection thereafter. Alterations in homeostasis in epithelia
due to severe CD4(+) T-cell depletion accompanied by changes in the cytokine and
chemokine production by IEL may play a role in the enteropathogenesis of SIV
infection.
PMID- 9658084
TI - Human immunodeficiency virus type 1 replication is modulated by host cyclophilin
A expression levels.
AB - Human immunodeficiency virus type 1 (HIV-1) Gag and the cellular protein
cyclophilin A form an essential complex in the virion core: virions produced by
proviruses encoding Gag mutants with decreased cyclophilin A affinity exhibit
attenuated infectivity, as do virions produced in the presence of the competitive
inhibitor cyclosporine. The A224E Gag mutant has no effect on cyclophilin A
affinity but renders HIV-1 replication cyclosporine resistant in Jurkat T cells.
In contrast, A224E mutant virus is dead in H9 T cells, although replication is
rescued by cyclosporine or by expression in cis of a Gag mutant that decreases
cyclophilin A-affinity. The observation that disruption of the Gag-cyclophilin A
interaction rescues A224E mutant replication in H9 cells prompted experiments
which revealed that, relative to Jurkat cells, H9 cells express greater
quantities of cyclophilin A. The resulting larger quantity of cyclophilin A shown
to be packaged into virions produced by H9 cells is presumably disruptive to the
A224E mutant virion core. Further evidence that increased cyclophilin A
expression in H9 cells is of functional relevance was provided by the finding
that Gag mutants with decreased cyclophilin A affinity are dead in Jurkat cells
but capable of replication in H9 cells. Similarly, cyclosporine concentrations
which inhibit wild-type HIV-1 replication in Jurkat cells stimulate HIV-1
replication in H9 cells. These results suggest that HIV-1 virion infectivity
imposes narrow constraints upon cyclophilin A stoichiometry in virions and that
infectivity is finely tuned by host cyclophilin A expression levels.
PMID- 9658085
TI - Transfectant influenza A viruses with long deletions in the NS1 protein grow
efficiently in Vero cells.
AB - We established a reverse genetics system for the nonstructural (NS) gene segment
of influenza A virus. This system is based on the use of the temperature
sensitive (ts) reassortant virus 25A-1. The 25A-1 virus contains the NS gene from
influenza A/Leningrad/134/57 virus and the remaining gene segments from A/Puerto
Rico (PR)/8/34 virus. This particular gene constellation was found to be
responsible for the ts phenotype. For reverse genetics of the NS gene, a plasmid
derived NS gene from influenza A/PR/8/34 virus was ribonucleoprotein transfected
into cells that were previously infected with the 25A-1 virus. Two subsequent
passages of the transfection supernatant at 40 degreesC selected viruses
containing the transfected NS gene derived from A/PR/8/34 virus. The high
efficiency of the selection process permitted the rescue of transfectant viruses
with large deletions of the C-terminal part of the NS1 protein. Viable
transfectant viruses containing the N-terminal 124, 80, or 38 amino acids of the
NS1 protein were obtained. Whereas all deletion mutants grew to high titers in
Vero cells, growth on Madin-Darby canine kidney (MDCK) cells and replication in
mice decreased with increasing length of the deletions. In Vero cells expression
levels of viral proteins of the deletion mutants were similar to those of the
wild type. In contrast, in MDCK cells the level of the M1 protein was
significantly reduced for the deletion mutants.
PMID- 9658086
TI - Biochemical analysis of the secreted and virion glycoproteins of Ebola virus.
AB - The glycoproteins expressed by a Zaire species of Ebola virus were analyzed for
cleavage, oligomerization, and other structural properties to better define their
functions. The 50- to 70-kDa secreted and 150-kDa virion/structural glycoproteins
(SGP and GP, respectively), which share the 295 N-terminal residues, are cleaved
near the N terminus by signalase. A second cleavage event, occurring in GP at a
multibasic site (RRTRR downward arrow) that is likely mediated by furin, results
in two glycoproteins (GP1 and GP2) linked by disulfide bonding. This furin
cleavage site is present in the same position in the GPs of all Ebola viruses
(R[R/K]X[R/K]R downward arrow), and one is predicted for Marburg viruses
(R[R/K]KR downward arrow), although in a different location. Based on the results
of cross-linking studies, we were able to determine that Ebola virion peplomers
are composed of trimers of GP1-GP2 heterodimers and that aspects of their
structure are similar to those of retroviruses, paramyxoviruses, and influenza
viruses. We also determined that SGP is secreted from infected cells almost
exclusively in the form of a homodimer that is joined by disulfide bonding.
PMID- 9658087
TI - Herpes simplex virus type 1 tegument protein VP22 induces the stabilization and
hyperacetylation of microtubules.
AB - The role of the herpes simplex virus type 1 tegument protein VP22 during
infection is as yet undefined. We have previously shown that VP22 has the unusual
property of efficient intercellular transport, such that the protein spreads from
single expressing cells into large numbers of surrounding cells. We also noted
that in cells expressing VP22 by transient transfection, the protein localizes in
a distinctive cytoplasmic filamentous pattern. Here we show that this pattern
represents a colocalization between VP22 and cellular microtubules. Moreover, we
show that VP22 reorganizes microtubules into thick bundles which are easily
distinguishable from nonbundled microtubules. These bundles are highly resistant
to microtubule-depolymerizing agents such as nocodazole and incubation at 4
degreesC, suggesting that VP22 has the capacity to stabilize the microtubule
network. In addition, we show that the microtubules contained in these bundles
are modified by acetylation, a marker for microtubule stability. Analysis of
infected cells by both immunofluorescence and measurement of microtubule
acetylation further showed that colocalization between VP22 and microtubules, and
induction of microtubule acetylation, also occurs during infection. Taken
together, these results suggest that VP22 exhibits the properties of a classical
microtubule-associated protein (MAP) during both transfection and infection. This
is the first demonstration of a MAP encoded by an animal virus.
PMID- 9658088
TI - Brefeldin A inhibits cell-free, de novo synthesis of poliovirus.
AB - Brefeldin A (BFA), an inhibitor of intracellular vesicle-dependent secretory
transport, is a potent inhibitor of poliovirus RNA replication in infected cells.
We have determined that the unknown mechanism of BFA inhibition of replication is
reproduced in the cell-free poliovirus translation, replication, and
encapsidation system. Furthermore, we provide evidence suggesting that the
cellular mechanism targeted by BFA, the GTP-dependent synthesis of secretory
transport vesicles, may be involved in viral RNA replication in the system via a
soluble cellular GTP-binding and -hydrolyzing activity. This activity is related
to the ARF (ADP-ribosylation factor) family of GTP-binding proteins. ARFs are
required for the formation of several classes of secretory vesicles, and some
family members are indirectly inactivated by BFA. Peptides that function as
competitive inhibitors of ARF activity in cell-free transport systems also
inhibit poliovirus RNA replication, and this inhibitory effect can be countered
by the addition of exogenous ARF. We suggest that BFA inhibition of replication
is diagnostic of a requirement for ARF activity in the cell-free system.
PMID- 9658089
TI - Naturally occurring human immunodeficiency virus type 1 long terminal repeats
have a frequently observed duplication that binds RBF-2 and represses
transcription.
AB - Approximately 38% of human immunodeficiency virus type 1 (HIV-1)-infected
patients within the Vancouver Lymphadenopathy-AIDS Study have proviruses bearing
partial 15- to 34-nucleotide duplications upstream of the NF-kappaB binding sites
within the 5' long terminal repeat (LTR). This most frequent naturally occurring
length polymorphism (MFNLP) of the HIV-1 5' LTR encompasses potential binding
sites for several candidate transcription factors, including TCF-1alpha/hLEF, c
Ets, AP-4, and Ras-responsive binding factor 2 (RBF-2) (M. C. Estable et al., J.
Virol. 70:4053-4062, 1996). RBF-2 and an apparently related factor, RBF-1, bind
to at least four cis elements within the LTR which are required for full
transcriptional responsiveness to protein-tyrosine kinases and v-Ras (B. Bell and
I. Sadowski, Oncogene 13:2687-2697, 1996). Here we demonstrate that
representative MFNLPs from two patients specifically bind RBF-2. In both cases,
deletion of the MFNLP caused elevated LTR-directed transcription in cells
expressing RBF-2 but not in cells with undetectable RBF-2. RBF-1, but not RBF-2,
appears to contain the Ets transcription factor family member
GABPalpha/GABPbeta1. Taken together with the fact that every MFNLP from a
comparative study of over 500 LTR sequences from 42 patients contains a predicted
binding site for RBF-2, our data suggest that the MFNLP is selected in vivo
because it provides a duplicated RBF-2 cis element, which may limit transcription
in monocytes and activated T cells.
PMID- 9658090
TI - The second extracellular loop of CXCR4 determines its function as a receptor for
feline immunodeficiency virus.
AB - The feline homolog of the alpha-chemokine receptor CXCR4 has recently been shown
to support cell-cell fusion mediated by CXCR4-dependent strains of human
immunodeficiency virus (HIV) and strains of feline immunodeficiency virus (FIV)
that have been selected for growth in the Crandell feline kidney (CrFK) cell
line. In this report we demonstrate that expression of CXCR4 alone is sufficient
to render cells from diverse species permissive for fusion with FIV-infected
cells, suggesting that CXCR4 is the sole receptor for CrFK-tropic strains of FIV,
analogous to CD4-independent strains of HIV-2. To identify the regions of CXCR4
involved in fusion mediated by FIV, we screened panels of chimeric CXCR4
molecules for the ability to support fusion with FIV-infected cells. Human CXCR4
supported fusion more efficiently than feline CXCR4 and feline/human CXCR4
chimeras, suggesting that the second and third extracellular loops of human CXCR4
contain a critical determinant for receptor function. Rat/human CXCR4 chimeras
suggested that the second extracellular loop contained the principal determinant
for receptor function; however, chimeras constructed between human CXCR2 and
CXCR4 revealed that the first and third loops of CXCR4 contribute to the FIV Env
binding site, as replacement of these domains with the corresponding domains of
CXCR2 rendered the molecule nonfunctional in fusion assays. Mutation of the DRY
motif and the C-terminal cytoplasmic tail of CXCR4 did not affect the ability of
the molecule to support fusion, suggesting that neither signalling via G proteins
nor receptor internalization was required for fusion mediated by FIV; similarly,
truncation of the N terminus of CXCR4 did not affect the function of the molecule
as a receptor for FIV. CXCR4-transfected feline cells were rendered permissive
for infection with both the CrFK-tropic PET isolate of FIV and the CXCR4
dependent RF strain of HIV-1, and susceptibility to infection correlated well
with ability to support fusion. The data suggest that the second extracellular
loop of CXCR4 is the major determinant of CXCR4 usage by FIV.
PMID- 9658091
TI - Viral genetic evolution in macaques infected with molecularly cloned simian
immunodeficiency virus correlates with the extent of persistent viremia.
AB - Genetic evolution of the simian immunodeficiency virus (SIV) envelope
glycoprotein was evaluated in a group of six macaques (Macaca nemestrina)
infected with the molecularly cloned, moderately pathogenic SIVsm62d. The extent
of envelope evolution was subsequently evaluated within the context of the
individual pattern of viremia and disease outcome. Two macaques in this cohort
developed AIDS by 1.5 years postinoculation (progressors), whereas the remaining
four macaques remained asymptomatic (nonprogressors). Compared with the
nonprogressor macaques, the two progressor macaques exhibited higher persistent
plasma viremia, higher homologous neutralizing antibody titers, and more
extensive mutation and evolution in the V1 region of envelope. Although clearly
distinct in each of these parameters from the progressors, the four
nonprogressors exhibited more individual variability with respect to the extent
of persistent viremia and genetic evolution of the V1 region of envelope. The
extent of V1 envelope varied from no apparent V1 evolution in a macaque with good
viral containment to extensive evolution in one macaque with persistent viremia.
This study underscores the critical role of persistent replication in the genetic
evolution of SIV.
PMID- 9658092
TI - In vivo Ty1 reverse transcription can generate replication intermediates with
untidy ends.
AB - Ty1 retrotransposition, like retroviral replication, is a complex series of
events requiring reverse transcription of an RNA intermediate, RNA-primed minus-
and plus-strand DNA synthesis, multiple strand transfers, and precise cleavages
of the template and primers by RNase H. In this report, we examine the structure
of in vivo Ty1 replication intermediates, specifically with regard to the
behavior of reverse transcriptase upon reaching template ends and to the
precision with which RNase H might generate these ends. While the expected 3'
termini were always identified, terminal nontemplated bases were also observed at
all of the RNA and DNA template ends examined. Nontemplated A residues were most
common at all 3' ends, although C residues were preferentially added to minus
strand termini paused at the 5' end of capped Ty1 RNA. In addition, we observed
that RNase H removal of the tRNA primer and of the polypurine tract was not
always precise or efficient. Finally, we noted numerous instances of Ty1 reverse
transcriptase transferring from normal Ty1 template ends to various tRNA
templates, with continued synthesis to specific modified bases. A similar pattern
was obtained for Ty2, indicating that template ends offer unique opportunities
for these two related reverse transcriptases to generate errors.
PMID- 9658093
TI - Human T-cell leukemia virus type 1 reverse transcriptase (RT) originates from the
pro and pol open reading frames and requires the presence of RT-RNase H (RH) and
RT-RH-integrase proteins for its activity.
AB - The first description of an active form of a recombinant human T-cell leukemia
virus type 1 (HTLV-1) reverse transcriptase (RT) and subsequent predictions of
its amino acid sequence and quaternary structure are reported here. By using
amino acid alignment methods, the NH2 and COOH termini of the RT, RNase H (RH),
and integrase (IN) domains of the Pol polyprotein were determined. The HTLV-1 RT
seems to be unique since its NH2 terminus is probably encoded by the pro open
reading frame (ORF) fused downstream, via a transframe peptide, to the
polypeptide encoded by the pol ORF. The HTLV-1 Pol amino acid sequence was
revealed to be highly similar to that of Rous sarcoma virus (RSV), particularly
at the RT-RH hinge region. These two domains remain linked for RSV; this may also
be the case for HTLV-1. In light of these results, RT, RT-RH, and RT-RH-IN genes
were constructed and introduced into His-tagged protein expression vectors. The
corresponding proteins were synthesized in vitro, and the DNA polymerase
activities of different protein combinations were tested. Solely the RT-RH-RT-RH
IN combination was found to have a significant activity level. Velocity
sedimentation analysis suggested that the HTLV-1 RT-RH and RT-RH-IN monomers are
likely associated in an oligomeric structure, probably of the alpha3/beta type.
PMID- 9658094
TI - Involvement of aminopeptidase N (CD13) in infection of human neural cells by
human coronavirus 229E.
AB - Attachment to a cell surface receptor can be a major determinant of virus
tropism. Previous studies have shown that human respiratory coronavirus HCV-229E
uses human aminopeptidase N (hAPN [CD13]) as its cellular receptor for infection
of lung fibroblasts. Although human coronaviruses are recognized respiratory
pathogens, occasional reports have suggested their possible neurotropism. We have
previously shown that human neural cells, including glial cells in primary
cultures, are susceptible to human coronavirus infection in vitro (A. Bonavia, N.
Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). However, the
only reported expression of hAPN in the nervous system is at the level of nerve
synapses. Therefore, we asked whether hAPN is utilized as a cellular receptor for
infection of these human neural cell lines. Using flow cytometry, we were able to
show the expression of hAPN on the surfaces of various human neuronal and glial
cell lines that are susceptible to HCV-229E infection. An hAPN-specific
monoclonal antibody (WM15), but not control antibody, inhibited the attachment of
radiolabeled HCV-229E to astrocytic, neuronal, and oligodendrocytic cell lines. A
correlation between the apparent amount of cell surface hAPN and the level of
virus attachment was observed. Furthermore, the presence of WM15 inhibited virus
infection of these cell lines, as detected by indirect immunofluorescence. These
results indicate that hAPN (CD13) is expressed on neuronal and glial cell lines
in vitro and serves as the receptor for infection by HCV-229E. This further
strengthens the neurotropic potential of this human respiratory virus.
PMID- 9658095
TI - In vivo pathogenesis of a human immunodeficiency virus type 1 reporter virus.
AB - Our understanding of human immunodeficiency virus type 1 (HIV-1)-induced
pathogenesis is hampered by the inability to detect HIV-1 gene expression in
infected viable cells. In this report, we describe two HIV-1 reporter constructs
that are replication competent and cytopathic in vivo. These constructs contain
DNA regions of two different lengths that bear the cDNA for the murine heat
stable antigen in the vpr region of a CXCR4-tropic virus. We used the SCID-hu
mouse model and these reporter viruses to perform detailed kinetic studies of HIV
1 infection of human thymocytes in vivo. We document that the CD4(+)/CD8(+)
thymocytes are the first to express virus and that this subset demonstrates the
most rapid and extensive HIV-1-induced cell depletion. Following depletion of
this subset, subsequent virus expression occurs predominantly in phenotypically
CD4(-) cells, suggesting that CD4 down-regulation occurs in HIV-1-infected
thymocytes in vivo. These results demonstrate the utility of these HIV-1 reporter
constructs to monitor HIV pathogenesis in vitro and in vivo.
PMID- 9658096
TI - Identification of a human immunodeficiency virus type 2 (HIV-2) encapsidation
determinant and transduction of nondividing human cells by HIV-2-based lentivirus
vectors.
AB - Although previous lentivirus vector systems have used human immunodeficiency
virus type 1 (HIV-1), HIV-2 is less pathogenic in humans and is amenable to
pathogenicity testing in a primate model. In this study, an HIV-2 molecular clone
that is infectious but apathogenic in macaques was used to first define cis
acting regions that can be deleted to prevent HIV-2 genomic encapsidation and
replication without inhibiting viral gene expression. Lentivirus encapsidation
determinants are complex and incompletely defined; for HIV-2, some deletions
between the major 5' splice donor and the gag open reading frame have been shown
to minimally affect encapsidation and replication. We find that a larger deletion
(61 to 75 nucleotides) abrogates encapsidation and replication but does not
diminish mRNA expression. This deletion was incorporated into a replication
defective, envelope-pseudotyped, three-plasmid HIV-2 lentivirus vector system
that supplies HIV-2 Gag/Pol and accessory proteins in trans from an HIV-2
packaging plasmid. The HIV-2 vectors efficiently transduced marker genes into
human T and monocytoid cell lines and, in contrast to a murine leukemia virus
based vector, into growth-arrested HeLa cells and terminally differentiated human
macrophages and NTN2 neurons. Vector DNA could be detected in HIV-2 vector
transduced nondividing CD34(+) CD38(-) human hematopoietic progenitor cells but
not in those cells transduced with murine vectors. However, stable integration
and expression of the reporter gene could not be detected in these hematopoietic
progenitors, leaving open the question of the accessibility of these cells to
stable lentivirus transduction.
PMID- 9658097
TI - Moloney murine leukemia virus envelope protein subunits, gp70 and Pr15E, form a
stable disulfide-linked complex.
AB - The nature and stability of the interactions between the gp70 and Pr15E/p15E
molecules of murine leukemia virus (MLV) have been disputed extensively. To
resolve this controversy, we have performed quantitative biochemical analyses on
gp70-Pr15E complexes formed after independent expression of the amphotropic and
ecotropic Moloney MLV env genes in BHK-21 cells. We found that all cell
associated gp70 molecules are disulfide linked to Pr15E whereas only a small
amount of free gp70 is released by the cells. The complexes were resistant to
treatment with reducing agents in vivo, indicating that the presence and
stability of the disulfide interaction between gp70 and Pr15E are not dependent
on the cellular redox state. However, disulfide-bonded Env complexes were
disrupted in lysates of nonalkylated cells in a time-, temperature-, and pH
dependent fashion. Disruption seemed not to be caused by a cellular factor but is
probably due to a thiol-disulfide exchange reaction occurring within the Env
complex after solubilization. The possibility that alkylating agents induce the
formation of the intersubunit disulfide linkage was excluded by showing that
disulfide-linked gp70-Pr15E complexes exist in freshly made lysates of
nonalkylated cells and that disruption of the complexes can be prevented by
lowering the pH. Together, these data establish that gp70 and Pr15E form a stable
disulfide-linked complex in vivo.
PMID- 9658098
TI - Template-dependent initiation of Sindbis virus RNA replication in vitro.
AB - Recent insights into the early events in Sindbis virus RNA replication suggest a
requirement for either the P123 or P23 polyprotein, as well as mature nsP4, the
RNA-dependent RNA polymerase, for initiation of minus-strand RNA synthesis. Based
on this observation, we have succeeded in reconstituting an in vitro system for
template-dependent initiation of SIN RNA replication. Extracts were isolated from
cells infected with vaccinia virus recombinants expressing various SIN proteins
and assayed by the addition of exogenous template RNAs. Extracts from cells
expressing P123C>S, a protease-defective P123 polyprotein, and nsP4 synthesized a
genome-length minus-sense RNA product. Replicase activity was dependent upon
addition of exogenous RNA and was specific for alphavirus plus-strand RNA
templates. RNA synthesis was also obtained by coexpression of nsP1, P23C>S, and
nsP4. However, extracts from cells expressing nsP4 and P123, a cleavage-competent
P123 polyprotein, had much less replicase activity. In addition, a P123
polyprotein containing a mutation in the nsP2 protease which increased the
efficiency of processing exhibited very little, if any, replicase activity. These
results provide further evidence that processing of the polyprotein inactivates
the minus-strand initiation complex. Finally, RNA synthesis was detected when
soluble nsP4 was added to a membrane fraction containing P123C>S, thus providing
a functional assay for purification of the nsP4 RNA polymerase.
PMID- 9658099
TI - Characterization of a live-attenuated retroviral vaccine demonstrates protection
via immune mechanisms.
AB - Live-attenuated retroviruses have been shown to be effective retroviral vaccines,
but currently little is known regarding the mechanisms of protection. In the
present studies, we used Friend virus as a model to analyze characteristics of a
live-attenuated vaccine in protection against virus-induced disease. Highly
susceptible mice were immunized with nonpathogenic Friend murine leukemia helper
virus (F-MuLV), which replicates poorly in adult mice. Further attenuation of the
vaccine virus was achieved by crossing the Fv-1 genetic resistance barrier. The
minimum dose of vaccine virus required to protect 100% of the mice against
challenge with pathogenic Friend virus complex was determined to be 10(3) focus
forming units of attenuated virus. Live vaccine virus was necessary for induction
of immunity, since inactivated F-MuLV did not induce protection. To determine
whether immune cells mediated protection, spleen cells from vaccinated donor mice
were adoptively transferred into syngeneic recipients. The results indicated that
immune mechanisms rather than viral interference mediated protection.
PMID- 9658100
TI - Critical role for CD4(+) T cells in controlling retrovirus replication and spread
in persistently infected mice.
AB - Reactivations of persistent viral infections pose a significant medical problem
in immunocompromised cancer, transplant, and AIDS patients, yet little is known
about how persistent viral infections are immunologically controlled. Here we
describe a mouse model for investigating the role of the immune response in
controlling a persistent retroviral infection. We demonstrate that, following
recovery from acute Friend virus infection, a small number of B cells evade
immunological destruction and harbor persistent virus. In vivo depletions of T
cell subsets in persistently infected mice revealed a critical role for CD4(+) T
cells in controlling virus replication, spread to the erythroid lineage, and
induction of erythroleukemia. The CD4(+) T-cell effect was independent of CD8(+)
T cells and in some cases was also independent of virus-neutralizing antibody
responses. Thus, the CD4(+) T cells may have had a direct antiviral effect. These
results may have relevance for human immunodeficiency virus (HIV) infections
where loss of CD4(+) T cells is associated with an increase in HIV replication,
reactivation of persistent viruses, and a high incidence of virus-associated
cancers.
PMID- 9658101
TI - Changing the site of initiation of plus-strand DNA synthesis inhibits the
subsequent template switch during replication of a hepadnavirus.
AB - Unique to hepadnavirus reverse transcription is the process of primer
translocation, in which the RNA primer for the initiation of plus-strand DNA
synthesis is generated at one site on its template, DR1, and is moved to a new
site, DR2. For duck hepatitis B virus (DHBV), DR2 is located within 50
nucleotides of the 5' end of the minus-strand DNA template. When the synthesis of
plus-strand DNA proceeds to the 5' terminus of the minus strand, the 3' end of
the minus strand becomes the template for DNA synthesis. This switch in templates
circularizes the nascent genome and is required for the genesis of the relaxed
circular form of the DNA and the mature capsid. Maturation of the capsid is a
prerequisite for virus egress. We have analyzed a series of DHBV variants in
which plus-strand DNA synthesis was initiated from a new position relative to the
5' end of the template. For these variants, the subsequent circularization was
inhibited. We found that when the number of nucleotides between the site of
initiation of plus-strand DNA synthesis and the 5' end of its template was
restored to 54 nucleotides, circularization was substantially restored. These
results mean that the process of circularization is influenced by the earlier
steps in DNA replication. This sensitivity is consistent with the notion that
this region of the nascent genome is in a dynamic structure that is crucial for
successful DNA replication.
PMID- 9658102
TI - Apoptosis induction by the binding of the carboxyl terminus of human
immunodeficiency virus type 1 gp160 to calmodulin.
AB - The role of calmodulin (CaM) in apoptosis induced by gp160 of human
immunodeficiency virus type 1 was investigated with cells undergoing single-cell
killing. These cells were found to express, under the control of an inducible
promoter, wild-type gp160 or mutant gp160 devoid of various lengths of the
carboxyl terminus. Immunoprecipitation accompanied by immunoblotting revealed
binding of CaM to wild-type gp160 but not to mutant gp160 bearing a carboxyl
terminus with a deletion spanning more than five amino acid residues. A
significant coenzyme activity was detected in the CaM bound to gp160 even in the
presence of a Ca2+ chelater, EGTA. The cells forming this gp160-CaM complex
exhibited an elevated intracellular Ca2+ level followed by DNA fragmentation,
which is a hallmark of apoptosis, and finally cell killing, while the cells not
forming this complex did not show any significant elevation in Ca2+ level or DNA
fragmentation. These results thus indicated that CaM plays a key role in gp160
induced apoptosis.
PMID- 9658103
TI - The disruption of ND10 during herpes simplex virus infection correlates with the
Vmw110- and proteasome-dependent loss of several PML isoforms.
AB - The small nuclear structures known as ND10 or PML nuclear bodies have been
implicated in a variety of cellular processes including response to stress and
interferons, oncogenesis, and viral infection, but little is known about their
biochemical properties. Recently, a ubiquitin-specific protease enzyme (named
HAUSP) and a ubiquitin-homology family protein (PIC1) have been found associated
with ND10. HAUSP binds strongly to Vmw110, a herpesvirus regulatory protein which
has the ability to disrupt ND10, while PIC1 was identified as a protein which
interacts with PML, the prototype ND10 protein. We have investigated the role of
ubiquitin-related pathways in the mechanism of ND10 disruption by Vmw110 and the
effect of virus infection on PML stability. The results show that the disruption
of ND10 during virus infection correlates with the loss of several PML isoforms
and this process is dependent on active proteasomes. The PML isoforms that are
most sensitive to virus infection correspond closely to those which have recently
been identified as being covalently conjugated to PIC1. In addition, a large
number of PIC1-protein conjugates can be detected following transfection of a
PIC1 expression plasmid, and many of these are also eliminated in a Vmw110
dependent manner during virus infection. These observations provide a biochemical
mechanism to explain the observed effects of Vmw110 on ND10 and suggest a simple
yet powerful mechanism by which Vmw110 might function during virus infection.
PMID- 9658104
TI - Role of the transcription start site core region and transcription factor YY1 in
Rous sarcoma virus long terminal repeat promoter activity.
AB - The Rous sarcoma virus (RSV) long terminal repeat (LTR) contains a
transcriptionally potent enhancer and promoter that functions in a variety of
cell types. Previous studies have identified the viral sequences required for
enhancer activity, and characterization of these elements has provided insight
into the mechanism of RSV transcriptional activity. The objective of this study
was to better define the RSV LTR promoter by examining the transcription start
site core (TSSC) region. Deletion of the TSSC resulted in complete loss of
transcriptional activity despite the presence of a functional TATA box,
suggesting that the TSSC is required for viral expression. Homologies within the
TSSC to the DNA binding motif of YY1 suggested that it might regulate promoter
activity. YY1 has been shown to regulate transcription in some cellular genes and
viral promoters by binding to sites overlapping the transcription start site. Gel
shift assays using YY1 antibody identified YY1 as one of three complexes that
bound to the TSSC. Mutation of the YY1 binding site reduced RSV transcriptional
activity by more than 50%, suggesting that YY1, in addition to other TSSC-binding
factors, regulates RSV transcription. Furthermore, in vitro transcription assays
performed with Drosophila embryo extract (devoid of YY1 activity) showed
decreased levels of RSV transcription, while transient transfection experiments
overexpressing YY1 demonstrated that YY1 could transactivate the RSV LTR
approximately 6- to 7-fold. We propose that the TSSC plays a vital role in RSV
transcription and that this function is partially carried out by the
transcription factor YY1.
PMID- 9658105
TI - Involvement of human CRM1 (exportin 1) in the export and multimerization of the
Rex protein of human T-cell leukemia virus type 1.
AB - We investigated the role of human CRM1 (hCRM1) (exportin 1) in the function of
Rex protein encoded by human T-cell leukemia virus type 1. hCRM1 promoted the
export of Rex protein from the nucleus to the cytoplasm. A Rex protein with a
mutation in the activation domain, RexM90, lost both the ability to bind to hCRM1
and the ability to multimerize. The overexpression of hCRM1 complemented the
functional defects of RexM64, which contains a mutation in the multimerization
domain of Rex. A dominant-negative mutant of Rex which sequesters cofactors of
Rex abrogated multimerization as well as the activity of the wild-type Rex
protein. These two functions were simultaneously restored by the overexpression
of hCRM1. Taken together, these results suggest that hCRM1 plays important roles
in the multimerization and export of Rex protein.
PMID- 9658106
TI - In vivo effects of mutations in woodchuck hepatitis virus enhancer II.
AB - Woodchuck hepatitis virus (WHV) enhancer II (EnII) is located upstream of the
major pregenomic RNA promoter and is thought to play an important role in the
insertional activation of the N-myc2 gene during WHV hepatocarcinogenesis. WHV
EnII is recognized by at least three host transcription factors: HNF-1, HNF-4,
and Oct-1. Here, the roles of these EnII-binding factors in viral transcription
and replication have been further examined. In HepG2 cells transiently
transfected with a chloramphenicol acetyltransferase (CAT) gene whose expression
is dependent upon EnII, mutations in either the HNF-1 or the HNF-4 site strongly
reduced CAT activity, while ablation of the Oct-1 site decreased CAT expression
only twofold. Mutations in more than one site completely abolished reporter
expression. These same mutations were also tested in an overlength WHV genome for
their impact on viral replication and gene expression. In transfected HepG2
cells, lesions in the HNF-1 site inactivated pregenomic RNA expression and viral
reverse transcription, with only minimal effects on the expression of other viral
mRNAs. By contrast, Oct-1 site lesions had no effect on either viral RNA
synthesis or DNA replication, and HNF-4 site lesions produced a modest reduction
of pregenomic RNA but had no impact on viral DNA synthesis. Testing of the
mutants in susceptible woodchucks revealed that, as expected, viruses with
lesions in the HNF-1 site were nearly noninfectious, while mutants with lesions
at the Oct-1 site were fully replication competent. HNF-4 site mutants were
replication competent but may display reduced levels of replication in the intact
animal host. We conclude that (i) EnII is primarily devoted to the regulation of
pregenomic RNA in WHV, (ii) HNF-1 is essential for EnII function in vivo, and
(iii) HNF-4 plays a demonstrable but adjunctive role in EnII function.
PMID- 9658107
TI - Identification of a cytotoxic T-lymphocyte response to the novel BARF0 protein of
Epstein-Barr virus: a critical role for antigen expression.
AB - The Epstein-Barr virus (EBV)-encoded BARF0 open reading frame gene products are
consistently expressed in EBV-positive Burkitt's lymphoma (BL) cell lines,
nasopharyngeal carcinoma cell lines, and lymphoblastoid cell lines (LCLs). Here
we show that the BARF0 sequence includes an HLA A*0201-restricted cytotoxic T
lymphocyte (CTL) epitope. By using theoretically predicted HLA A2 binding motifs
and peptide-loaded antigen presentation-deficient T2 cells, polyclonal BARF0
specific CD8(+) CTLs were isolated from four different healthy EBV-seropositive
donors but not from two seronegative donors. These CTL lines recognized the
peptide epitope LLWAARPRL, which was found to be conserved in 33 of 34 virus
strains originating from Caucasian, African, and Asian individuals. The BARF0
specific CTL lines could lyse EBV-negative BL cells stably transfected with the
BARF0 gene but did not kill HLA A2-matched EBV-positive BL cells and LCLs in a
standard 51Cr release assay. Reverse transcriptase PCR analysis demonstrated that
these EBV-positive cell lines expressed significantly lower levels of BARF0 mRNA
than transfected cells. This data indicated that the BARF0 epitope could be
endogenously processed; however, antigen levels in the target cell were a
limiting factor for the effective interaction between BARF0-expressing cells and
CTLs. The limited expression of BARF0 antigen in EBV-infected BL cells and LCLs
might contribute to the escape of immune recognition from virus-specific CTLs
present in the host.
PMID- 9658108
TI - The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor.
AB - The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA was isolated from a cDNA
expression library of African green monkey kidney (AGMK) cells by using
protective monoclonal antibody (MAb) 190/4, which blocks the binding of hepatitis
A virus (HAV) to AGMK cells. The HAVcr-1 cDNA codes for havcr-1, a 451-amino-acid
class I integral-membrane mucin-like glycoprotein of unknown natural function. To
determine the existence of a human homolog(s) of HAVcr-1 (huHAVcr-1), we used
HAVcr-1-specific primers to amplify cDNAs from human liver and kidney mRNA by
reverse transcription-PCR. Nucleotide sequence analysis revealed that the
amplified liver and kidney huHAVcr-1 cDNAs were identical and that they coded for
a 359-amino-acid glycoprotein, termed huhavcr-1, which was approximately 79%
identical to havcr-1. The six Cys residues of the extracellular domain of havcr-1
and its first N-glycosylation site were conserved in huhavcr-1. However, the
number of hexameric repeats of the mucin-like region was reduced from 27 in havcr
1 to 13 in huhavcr-1. In addition, 12 C-terminal amino acids in the cytoplasmic
domain of huhavcr-1 were deleted. Northern blot analysis of poly(A) RNA showed
that huhavcr-1 is expressed in every organ analyzed, including the liver, small
intestine, colon, and spleen, and that it is expressed at higher levels in the
kidney and testis. Although dog cells transfected with the huHAVcr-1 cDNA did not
express the protective 190/4 epitope, they bound hepatitis A virus (HAV) and
gained limited susceptibility to HAV infection. Treatment with MAb 190/4 did not
protect AGMK cell transfectants expressing huhavcr-1 against HAV, suggesting that
HAV infected these cells via the huhavcr-1 receptor and not the endogenously
expressed havcr-1, which was blocked by MAb 190/4. Our data demonstrate that
huhavcr-1 is a binding receptor for HAV and suggest that it is also a functional
receptor for HAV.
PMID- 9658109
TI - Compensatory point mutations in the human immunodeficiency virus type 1 Gag
region that are distal from deletion mutations in the dimerization initiation
site can restore viral replication.
AB - The dimerization initiation site (DIS), downstream of the long terminal repeat
within the human immunodeficiency virus type 1 (HIV-1) genome, can form a stem
loop structure (SL1) that has been shown to be involved in the packaging of viral
RNA. In order to further determine the role of this region in the virus life
cycle, we deleted the 16 nucleotides (nt) at positions +238 to +253 within SL1 to
generate a construct termed BH10-LD3 and showed that this virus was impaired in
viral RNA packaging, viral gene expression, and viral replication. Long-term
culture of these mutated viruses in MT-2 cells, i.e., 18 passages, yielded
revertant viruses that possessed infectivities similar to that of the wild type.
Cloning and sequencing showed that these viruses retained the original 16-nt
deletion but possessed two additional point mutations, which were located within
the p2 and NC regions of the Gag coding region, respectively, and which were
therefore named MP2 and MNC. Site-directed mutagenesis studies revealed that both
of these point mutations were necessary to compensate for the 16-nt deletion in
BH10-LD3. A construct with both the 16-nt deletion and the MP2 mutation, i.e.,
LD3-MP2, produced approximately five times more viral protein than BH10-LD3,
while the MNC mutation, i.e., construct LD3-MNC, reversed the defects in viral
RNA packaging. We also deleted nt +261 to +274 within the 3' end of SL1 and
showed that the diminished infectivity of the mutated virus, termed BH10-LD4,
could also be restored by the MP2 and MNC point mutations. Therefore,
compensatory mutations within the p2 and NC proteins, distal from deletions
within the DIS region of the HIV genome, can restore HIV replication, viral gene
expression, and viral RNA packaging to control levels.
PMID- 9658110
TI - Protective role of gamma interferon during the recall response to influenza
virus.
AB - During secondary immune responses to influenza virus, virus-specific T memory
cells are a major source of gamma interferon (IFN-gamma). We assessed the
contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1)
virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68
(H3N2) virus. The IFN-gamma-/- mice displayed significantly reduced survival
rates subsequent to a challenge with various doses of the A/WSN/33 virus. This
was associated with an impaired ability of the IFN-gamma-/- mice to completely
clear the pulmonary virus by day 7 after the challenge, although significant
reduction of the virus titers was noted. However, the IFN-gamma-/- mice developed
type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to
the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution
assay for the estimation of CTL precursor frequency. The pulmonary recruitment of
T cells in IFN-gamma-/- mice was not dramatically affected, and the percentage of
CD4(+) and CD8(+) T cells was similar to that of wild-type mice. The T cells from
IFN-gamma-/- mice did not display a significant switch toward a Th2 profile.
Furthermore, the IFN-gamma-/- mice retained the ability to mount significant
titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies.
Together, these results are consistent with a protective role of IFN-gamma during
the heterologous response against influenza virus independently of the generation
and local recruitment of cross-reactive CTLs.
PMID- 9658111
TI - Gastrointestinal T lymphocytes retain high potential for cytokine responses but
have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency
virus infection compared to peripheral lymphocytes.
AB - Gastrointestinal complications in human immunodeficiency virus (HIV) infection
are indicative of impaired intestinal mucosal immune system. We used simian
immunodeficiency virus (SIV)-infected rhesus macaques as an animal model for HIV
to determine pathogenic effects of SIV on intestinal T lymphocytes. Intestinal
CD4(+) T-cell depletion and the potential for cytokine responses were examined
during SIV infection and compared with results for lymphocytes from lymph nodes
and blood. Flow cytometric analysis demonstrated severe depletion of CD4(+)CD8(-)
single-positive T cells and CD4(+)CD8(+) double-positive T cells in intestinal
lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) during
primary SIV infection which persisted through the entire course of SIV infection.
In contrast, CD4(+) T-cell depletion was gradual in peripheral lymph nodes and
blood. Flow cytometric analysis of intracellular gamma interferon (IFN-gamma) and
interleukin-4 (IL-4) production following short-term mitogenic activation
revealed that LPL retained same or higher capacity for IFN-gamma production in
all stages of SIV infection compared to uninfected controls, whereas peripheral
blood mononuclear cells displayed a gradual decline. The CD8(+) T cells were the
major producers of IFN-gamma. There was no detectable change in the frequency of
IL-4-producing cells in both LPL and peripheral blood mononuclear cells. Thus,
severe depletion of CD4(+) LPL and IEL in primary SIV infection accompanied by
altered cytokine responses may reflect altered T-cell homeostasis in intestinal
mucosa. This could be a mechanism of SIV-associated enteropathy and viral
pathogenesis. Dynamic changes in intestinal T lymphocytes were not adequately
represented in peripheral lymph nodes or blood.
PMID- 9658113
TI - T-Cell-independent immunoglobulin G responses in vivo are elicited by live-virus
infection but not by immunization with viral proteins or virus-like particles.
AB - Immunoglobulin G (IgG) responses to viruses are generally assumed to be T-cell
dependent (TD). Recently, however, polyomavirus (PyV) infection of T-cell
deficient (T-cell receptor beta chain [TCR-beta] -/- or TCR-betaxdelta -/-) mice
was shown to elicit a protective, T-cell-independent (TI) antiviral IgM and IgG
response. A repetitive, highly organized antigenic structure common to many TI
antigens is postulated to be important in the induction of antibody responses in
the absence of helper T cells. To test whether the repetitive structure of viral
antigens is essential and/or sufficient for the induction of TI antibodies, we
compared the abilities of three forms of PyV antigens to induce IgM and IgG
responses in T-cell-deficient mice: soluble capsid antigens (VP1), repetitive
virus-like particles (VLPs), and live PyV. Immunization with each of the viral
antigens resulted in IgM production. VLPs and PyV elicited 10-fold-higher IgM
titers than VP1, indicating that the highly organized, repetitive antigens are
more efficient in IgM induction. Antigen-specific TI IgG responses, however, were
detected only in mice infected with live PyV, not in VP1- or VLP-immunized mice.
These results suggest that the highly organized, repetitive nature of the viral
antigens is insufficient to account for their ability to elicit TI IgG response
and that signals generated by live-virus infection may be essential for the
switch to IgG production in the absence of T cells. Germinal centers were not
observed in T-cell-deficient PyV-infected mice, indicating that the germinal
center pathway of B-cell differentiation is TD even in the context of a virus
infection.
PMID- 9658112
TI - Steady-state plasma membrane expression of human cytomegalovirus gB is determined
by the phosphorylation state of Ser900.
AB - Human cytomegalovirus (HCMV) infection of an astrocytoma cell line (U373) or
human fibroblast (HF) cells results in a differential cell distribution of the
major envelope glycoprotein gB (UL55). This 906-amino-acid type I glycoprotein
contains an extracellular domain with a signal sequence, a transmembrane domain,
and a 135-amino-acid cytoplasmic tail with a consensus casein kinase II (CKII)
site located at Ser900. Since phosphorylation of proteins in the secretory
pathway is an important determinant of intracellular trafficking, the state of gB
phosphorylation in U373 and HF cells was examined. Analysis of cells expressing
wild-type gB and gB with site-specific mutations indicated that the glycoprotein
was equally phosphorylated at a single site, Ser900, in both U373 and HF cells.
To assess the effect of charge on gB surface expression in U373 cells, Ser900 was
replaced with an aspartate (Asp) or alanine (Ala) residue to mimic the
phosphorylated and nonphosphorylated states, respectively. Expression of the Asp
but not the Ala gB mutation resulted in an increase in the steady-state
expression of gB at the plasma membrane (PM) in U373 cells. In addition,
treatment of U373 cells with the phosphatase inhibitor tautomycin resulted in the
accumulation of gB at the PM. Interestingly, the addition of a charge at Ser900
trapped gB in a low-level cycling pathway at the PM, preventing trafficking of
the protein to the trans-Golgi network or other intracellular compartments.
Therefore, these results suggest that a tautomycin-sensitive phosphatase
regulates cell-specific PM retrieval of gB to intracellular compartments.
PMID- 9658114
TI - Dendritic cells transmit human immunodeficiency virus type 1 to monocytes and
monocyte-derived macrophages.
AB - Previous studies have shown that human immunodeficiency virus type 1 (HIV-1)
exploits dendritic cells (DC) to replicate and spread among CD4(+) T cells. To
explain the predominance of non-syncytium-inducing (NSI) over syncytium-inducing
(SI) strains during the initial viremia of HIV, we investigated the ability of
blood monocyte (Mo)-derived DC to transmit HIV-1 to CD4(+) cells of the
monocytoid lineage. First, we demonstrate that in our system, DC are able to
transmit NSI strains, but not SI strains, of HIV-1 to fresh blood Mo and to Mo
derived macrophages (MDM). To establish a productive infection, a 10-fold-lower
amount of virus was necessary for DC-mediated transmission of HIV-1 to Mo than in
case of cell-free infection. Second, immature CD83(-) DC (imDC) transmit virus to
Mo and MDM with higher efficacy compared to mature CD83(+) DC (maDC); this
finding is in contrast to data previously obtained with CD4(+) T cells. Third,
maturation from imDC to maDC efficiently silenced expression of beta2-integrins
CD11b, CD11c, and CD18 by maDC. Moreover, monoclonal antibody against CD18
inhibited transmission of HIV-1 from imDC to Mo. We propose that the adhesion
molecules of the CD11/CD18 family, involved in cell-cell interactions of DC with
the microenvironment, may play a major role in imDC-mediated HIV-1 infection of
Mo and MDM.
PMID- 9658115
TI - Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and
chickens from Hong Kong.
AB - Genes of an influenza A (H5N1) virus from a human in Hong Kong isolated in May
1997 were sequenced and found to be all avian-like (K. Subbarao et al., Science
279:393-395, 1998). Gene sequences of this human isolate were compared to those
of a highly pathogenic chicken H5N1 influenza virus isolated from Hong Kong in
April 1997. Sequence comparisons of all eight RNA segments from the two viruses
show greater than 99% sequence identity between them. However, neither isolate's
gene sequence was closely (>95% sequence identity) related to any other gene
sequences found in the GenBank database. Phylogenetic analysis demonstrated that
the nucleotide sequences of at least four of the eight RNA segments clustered
with Eurasian origin avian influenza viruses. The hemagglutinin gene phylogenetic
analysis also included the sequences from an additional three human and two
chicken H5N1 virus isolates from Hong Kong, and the isolates separated into two
closely related groups. However, no single amino acid change separated the
chicken origin and human origin isolates, but they all contained multiple basic
amino acids at the hemagglutinin cleavage site, which is associated with a highly
pathogenic phenotype in poultry. In experimental intravenous inoculation studies
with chickens, all seven viruses were highly pathogenic, killing most birds
within 24 h. All infected chickens had virtually identical pathologic lesions,
including moderate to severe diffuse edema and interstitial pneumonitis. Viral
nucleoprotein was most frequently demonstrated in vascular endothelium,
macrophages, heterophils, and cardiac myocytes. Asphyxiation from pulmonary edema
and generalized cardiovascular collapse were the most likely pathogenic
mechanisms responsible for illness and death. In summary, a small number of
changes in hemagglutinin gene sequences defined two closely related subgroups,
with both subgroups having human and chicken members, among the seven viruses
examined from Hong Kong, and all seven viruses were highly pathogenic in chickens
and caused similar lesions in experimental inoculations.
PMID- 9658116
TI - ORF1a-encoded replicase subunits are involved in the membrane association of the
arterivirus replication complex.
AB - Among the functions of the replicase of equine arteritis virus (EAV; family
Arteriviridae, order Nidovirales) are important viral enzyme activities such as
proteases and the putative RNA polymerase and RNA helicase functions. The
replicase is expressed in the form of two polyproteins (open reading frame 1a
[ORF1a] and ORF1ab), which are processed into 12 nonstructural proteins by three
viral proteases. In immunofluorescence assays, the majority of these cleavage
products localized to the perinuclear region of the cell. A dense granular and
vesicular staining was observed, which strongly suggested membrane association.
By using confocal microscopy and double-label immunofluorescence, the
distribution of the EAV replicase was shown to overlap with that of PDI, a
resident protein of the endoplasmic reticulum and intermediate compartment. An in
situ labeling of nascent viral RNA with bromo-UTP demonstrated that the membrane
bound complex in which the replicase subunits accumulate is indeed the site of
viral RNA synthesis. A number of ORF1a-encoded hydrophobic domains were
postulated to be involved in the membrane association of the arterivirus
replication complex. By using various biochemical methods (Triton X-114
extraction, membrane purification, and sodium carbonate treatment), replicase
subunits containing these domains were shown to behave as integral membrane
proteins and to be membrane associated in infected cells. Thus, contribution to
the formation of a membrane-bound scaffold for the viral replication
transcription complex appears to be an important novel function for the
arterivirus ORF1a replicase polyprotein.
PMID- 9658117
TI - Viral ribonucleoprotein complex formation and nucleolar-cytoplasmic
relocalization of nucleolin in poliovirus-infected cells.
AB - The poliovirus 3' noncoding region (3'NCR) is involved in the efficient synthesis
of viral negative-stranded RNA molecules. A strong interaction between a 105-kDa
host protein and the wild-type 3'NCR, but not with a replication-defective mutant
3'NCR, was detected. This 105-kDa protein was identified as nucleolin which
predominantly resides in the nucleolus and has been proposed to function in the
folding of rRNA precursor molecules. A functional role for nucleolin in viral
genome amplification was examined in a cell-free extract which has been shown to
support the assembly of infectious virus from virion RNA. At early times of viral
gene expression, extracts depleted of nucleolin produced less infectious virus
than extracts depleted of fibrillarin, another resident of the nucleolus,
indicating a functional role of nucleolin in the early stages of the viral life
cycle in this in vitro system. Immunofluorescence analysis of uninfected and
infected cells showed a nucleocytoplasmic relocalization of nucleolin, but not of
fibrillarin, in poliovirus-infected cells. Relocalization of nucleolin was not
simply a consequence of virally induced inhibition of translation or
transcription, because inhibitors of translation or transcription did not induce
nucleolar-cytoplasmic relocalization of nucleolin. These findings suggest a novel
virus-induced mechanism by which certain nucleolar proteins are selectively
redistributed in infected cells.
PMID- 9658118
TI - Human thymidine kinase can functionally replace herpes simplex virus type 1
thymidine kinase for viral replication in mouse sensory ganglia and reactivation
from latency upon explant.
AB - Herpes simplex virus type 1 thymidine kinase exhibits a strikingly broad
substrate specificity. It is capable of phosphorylating deoxythymidine and
deoxyuridine as does human thymidine kinase, deoxycytidine as does human
deoxycytidine kinase, the cytosolic kinase whose amino acid sequence it most
closely resembles, and thymidylate as does human thymidylate kinase. Following
peripheral inoculation of mice, viral thymidine kinase is ordinarily required for
viral replication in ganglia and for reactivation from latency following
ganglionic explant. To determine which activity of the viral kinase is important
for replication and reactivation in mouse ganglia, recombinant viruses lacking
viral thymidine kinase but expressing individual human kinases were constructed.
Each recombinant virus expressed the appropriate kinase activity with early
kinetics following infection of cultured cells. The virus expressing human
thymidine kinase exhibited thymidine phosphorylation activity equivalent to
approximately 5% of that of wild-type virus in a quantitative plaque
autoradiography assay. Nevertheless, it was competent for ganglionic replication
and reactivation following corneal inoculation of mice. The virus expressing
human thymidylate kinase was partially competent for these activities despite
failing to express detectable thymidine kinase activity. The virus expressing
human deoxycytidine kinase failed to replicate acutely in neurons or to
reactivate from latency. Therefore, it appears that low levels of thymidine
phosphorylation suffice to fulfill the role of the viral enzyme in ganglia and
that this role can be partially fulfilled by thymidylate kinase activity alone.
PMID- 9658119
TI - Actinomycin D inhibits human immunodeficiency virus type 1 minus-strand transfer
in in vitro and endogenous reverse transcriptase assays.
AB - In this report we demonstrate that human immunodeficiency virus type 1 (HIV-1)
minus-strand transfer, assayed in vitro and in endogenous reactions, is greatly
inhibited by actinomycin D. Previously we showed that HIV-1 nucleocapsid (NC)
protein (a nucleic acid chaperone catalyzing nucleic acid rearrangements which
lead to more thermodynamically stable conformations) dramatically stimulates HIV
1 minus-strand transfer by preventing TAR-dependent self-priming from minus
strand strong-stop DNA [(-) SSDNA]. Despite this potent activity, the addition of
NC to in vitro reactions with actinomycin D results in only a modest increase in
the 50% inhibitory concentration (IC50) for the drug. PCR analysis of HIV-1
endogenous reactions indicates that minus-strand transfer is inhibited by the
drug with an IC50 similar to that observed when NC is present in the in vitro
system. Taken together, these results demonstrate that NC cannot overcome the
inhibitory effect of actinomycin D on minus-strand transfer. Other experiments
reveal that at actinomycin D concentrations which severely curtail minus-strand
transfer, neither the synthesis of (-) SSDNA nor RNase H degradation of donor RNA
is affected; however, the annealing of (-) SSDNA to acceptor RNA is significantly
reduced. Thus, inhibition of the annealing reaction is responsible for
actinomycin D-mediated inhibition of strand transfer. Since NC (but not reverse
transcriptase) is required for efficient annealing, we conclude that actinomycin
D inhibits minus-strand transfer by blocking the nucleic acid chaperone activity
of NC. Our findings also suggest that actinomycin D, already approved for
treatment of certain tumors, might be useful in combination therapy for AIDS.
PMID- 9658120
TI - The immunogenic glycoprotein gp35-37 of human herpesvirus 8 is encoded by open
reading frame K8.1.
AB - Human herpesvirus 8 (HHV-8) is likely to be involved in the pathogenesis of
Kaposi's sarcoma (KS) and body cavity-based lymphomas (BCBLs). The HHV-8 genome
is primarily in a latent state in BCBL-derived cell lines like BCBL-1, but lytic
replication can be induced by phorbol esters (R. Renne, W. Zhang, B. Herndier, M.
McGrath, N. Abbey, D. Kedes, and D. E. Ganem, Nat. Med. 2:342-346, 1996). A 35-
to 37-kDa glycoprotein (gp35-37) is the polypeptide most frequently and
intensively recognized by KS patient sera on Western blots with induced BCBL-1
cells. Its apparent molecular mass is reduced to 30 kDa by digestion with peptide
N-glycosidase F. By searching the known HHV-8 genomic sequence for open reading
frames (ORF) with the potential to encode such a glycoprotein, an additional, HHV
8-specific reading frame was identified adjacently to ORF K8. This ORF, termed
K8.1, was found to be transcribed primarily into a spliced mRNA encoding a
glycoprotein of 228 amino acids. Recombinant K8.1 was regularly recognized by KS
patient sera in Western blots, and immunoaffinity-purified antibodies to
recombinant K8.1 reacted with gp35-37. This shows that the immunogenic gp35-37 is
encoded by HHV-8 reading frame K8.1, which will be a useful tool for studies of
HHV-8 epidemiology and pathogenesis.
PMID- 9658121
TI - Complete protein linkage map of poliovirus P3 proteins: interaction of polymerase
3Dpol with VPg and with genetic variants of 3AB.
AB - Poliovirus has evolved to maximize its genomic information by producing
multifunctional viral proteins. The P3 nonstructural proteins harbor various
activities when paired with different binding partners. These viral polypeptides
regulate host cell macromolecular synthesis and function as proteinases, as RNA
binding proteins, or as RNA-dependent RNA polymerase. A cleavage product of the
P3 region is the genome-linked protein VPg that is essential in the initiation of
RNA synthesis. We have used an inducible yeast two-hybrid system to analyze
directly protein-protein interactions among P3 proteins. Sixteen signals of homo-
or heterodimer interactions have been observed and have been divided into three
groups. Of interest is the newly discovered affinity of VPg to 3Dpol that
suggests direct interaction between these molecules in genome replication. A
battery of 3AB variants (eight clustered-charge-to-alanine changes and five
single-amino-acid mutations) has been used to map the binding determinants of 3AB
3AB interaction which were found to differ from the amino acids critical for the
3AB-3Dpol interaction. The viral proteinase 3Cpro was not found to interact with
other 3Cpro molecules or with any other P3 polypeptide in yeast cells, a result
confirmed by glutaraldehyde cross-linking. The weak apparent interaction between
3AB and 3CDpro scored in the yeast two-hybrid system was in contrast to a strong
signal by far-Western blotting. The results elucidate, in part, previous results
of biochemical and genetic analyses. The role of the interactions in RNA
replication is addressed.
PMID- 9658122
TI - Fowlpox virus encodes nonessential homologs of cellular alpha-SNAP, PC-1, and an
orphan human homolog of a secreted nematode protein.
AB - The genome of fowlpox virus (FWPV), type species of the Avipoxviridae, is
considerably rearranged compared with that of vaccinia virus (the prototypic
poxvirus and type species of the Orthopoxviridae) and is 30% larger. It is likely
that the genome of FWPV contains genes in addition to those found in vaccinia
virus, probably involved with its replication and survival in the chicken. A
7,470-bp segment of the FWPV genome has five open reading frames (ORFs), two of
which encode ankyrin repeat proteins, many examples of which have been found in
poxviruses. The remaining ORFs encode homologs of cellular genes not reported in
any other virus. ORF-2 encodes a homolog of the yeast Sec17p and mammalian SNAP
proteins, crucial to vesicular transport in the exocytic pathway. ORF-3 encodes a
homolog of an orphan human protein, R31240_2, encoded on 19p13.2. ORF-3 is also
homologous to three proteins (YLS2, YMV6, and C07B5.5) from the free-living
nematode Caenorhabditis elegans and to a 43-kDa antigen from the parasitic
nematode Trichinella spiralis. ORF-5 encodes a homolog of the mammalian plasma
cell antigen PC-1, a type II glycoprotein with exophosphodiesterase activity. The
ORFs are present in the virulent precursor, HP1, of the sequenced attenuated
virus (FP9) and are conserved in other strains of FWPV. They were shown, by
deletion mutagenesis, to be nonessential to virus replication in tissue culture.
RNA encoding the viral homolog of PC-1 is expressed strongly early and late in
infection, but RNAs encoding the homologs of SNAP and R31240_2 are expressed
weakly and late.
PMID- 9658123
TI - The high mobility group protein 1 is a coactivator of herpes simplex virus ICP4
in vitro.
AB - ICP4 is an activator of herpes simplex virus early and late gene transcription
during infection and in vitro can efficiently activate the transcription of a
core promoter template containing only a TATA box and an initiator element. In
this study, we noted that the extent of activation by ICP4 in vitro was highly
dependent on the purity of TFIID when recombinant TFIIB, TFIIE, and TFIIF were
used as sources of these factors. ICP4 efficiently activated transcription with a
crude TFIID fraction. However, when immunoaffinity-purified TFIID was used in
place of the less pure TFIID, ICP4 activated transcription to a significantly
lesser extent. This finding indicated that the crude TFIID fraction may contain
additional factors that serve as coactivators of ICP4. To test this hypothesis,
the crude TFIID preparation was further fractionated by gel filtration
chromatography. The TFIID that eluted from the column lacked the hypothesized
coactivator activity. A fraction well separated from TFIID contained an activity
that when added with the TFIID fraction resulted in higher levels of
transcription in the presence ICP4. Further purification of the coactivator
containing fraction resulted in the isolation of a single 30-kDa polypeptide
(p30). p30 was also shown to serve as a coactivator of ICP4 with immunoaffinity
purified TFIID; however, p30 had no effect on basal transcription. Amino acid
sequence analysis revealed that p30 was the high mobility group protein 1, which
has been shown to facilitate the formation of higher-order DNA-protein complexes.
PMID- 9658124
TI - Multiple enzymatic activities associated with recombinant NS3 protein of
hepatitis C virus.
AB - The hepatitis C virus (HCV) nonstructural 3 protein (NS3) contains at least two
domains associated with multiple enzymatic activities; a serine protease activity
resides in the N-terminal one-third of the protein, whereas RNA helicase activity
and RNA-stimulated nucleoside triphosphatase activity are associated with the C
terminal portion. To study the possible mutual influence of these enzymatic
activities, a full-length NS3 polypeptide of 67 kDa was expressed as a nonfusion
protein in Escherichia coli, purified to homogeneity, and shown to retain all
three enzymatic activities. The protease activity of the full-length NS3 was
strongly dependent on the activation by a synthetic peptide spanning the central
hydrophobic core of the NS4A cofactor. Once complexed with the NS4A-derived
peptide, the full-length NS3 protein and the isolated N-terminal protease domain
cleaved synthetic peptide substrates with comparable efficiency. We show that, as
in the case of the isolated protease domain, the protease activity of full-length
NS3 undergoes inhibition by the N-terminal cleavage products of substrate
peptides corresponding to the NS4A-NS4B and NS5A-NS5B. We have also characterized
and quantified the NS3 ATPase, RNA helicase, and RNA-binding activities under
optimized reaction conditions. Compared with the isolated N-terminal and C
terminal domains, recombinant full-length NS3 did not show significant
differences in the three enzymatic activities analyzed in independent in vitro
assays. We have further explored the possible interdependence of the NS3 N
terminal and C-terminal domains by analyzing the effect of polynucleotides on the
modulation of all NS3 enzymatic functions. Our results demonstrated that the
observed inhibition of the NS3 proteolytic activity by single-stranded RNA is
mediated by direct interaction with the protease domain rather than with the
helicase RNA-binding domain.
PMID- 9658125
TI - A role for herpesvirus saimiri orf14 in transformation and persistent infection.
AB - The product of open reading frame 14 (orf14) of herpesvirus saimiri (HVS)
exhibits significant homology with mouse mammary tumor virus superantigen. orf14
encodes a 50-kDa secreted glycoprotein, as shown previously (Z. Yao, E.
Maraskovsky, M. K. Spriggs, J. I. Cohen, R. J. Armitage, and M. R. Alderson, J.
Immunol. 156:3260-3266, 1996). orf14 expressed from recombinant baculovirus
powerfully induces proliferation of CD4-positive cells originating from several
different species. To study the role of orf14 in transformation, a mutant form of
HVS (HVS Deltaorf14) was constructed with a deletion in the orf14 gene. The
transforming potential of HVS Deltaorf14 was tested in cell culture and in common
marmosets. Parental HVS subgroup C strain 488 immortalized common marmoset T
lymphocytes in vitro to interleukin-2-independent growth, while the HVS
Deltaorf14 mutant did not produce such a growth transformation. In addition, HVS
Deltaorf14 was nononcogenic in common marmosets. In contrast to other
nononcogenic HVS mutant viruses which were repeatedly isolated from peripheral
blood mononuclear cells of infected marmosets for more than 5 months, HVS
Deltaorf14 did not persist at a high level in vivo. These results demonstrate
that orf14 of HVS is not required for replication but is required for
transformation and for high-level persistence in vivo.
PMID- 9658127
TI - Naturally occurring mutations define a novel function of the hepatitis B virus
core promoter in core protein expression.
AB - Functional analysis of naturally occurring hepatitis B virus (HBV) mutations is
crucial in understanding their impact on disease. We have recently identified two
mutations in the HBV core promoter of an HBV strain associated with fulminant
hepatitis leading to highly (15-fold) enhanced replication as a result of
increased viral encapsidation of pregenomic RNA into the core particles (T. F.
Baumert et al., J. Clin. Invest. 98:2268-2276, 1996). Functional studies in an
encapsidation assay had demonstrated that the increase in encapsidation was
largely independent of pregenomic RNA transcription. In this study, we define the
molecular mechanism whereby the two core promoter mutations (C to T at nucleotide
[nt] 1768 and T to A at nt 1770) result in enhanced viral encapsidation and
replication. The effect of these mutations leading to increased encapsidation is
mediated through enhanced core protein synthesis (15-fold) by the mutant virus.
The marked increase in core protein synthesis is largely a result of
posttranscriptional or translational effect of the mutations because the
mutations resulted in only a twofold increase in pregenomic RNA transcription. In
addition, this effect appears to be selective for core expression since reverse
transcriptase-polymerase expression was increased only twofold. trans
complementation analyses of HBV replication demonstrated that enhanced
replication occurred only when the mutations were provided together with the core
protein in trans, confirming the functional association of the core promoter
mutations and core protein expression. In addition, the effect of the mutations
appears to be quantitatively dependent on the strain background to which the
mutations were introduced. Our study suggests that the HBV core promoter
regulates core protein expression at both transcriptional and posttranscriptional
levels.
PMID- 9658126
TI - Cytoplasmic forms of human T-cell leukemia virus type 1 Tax induce NF-kappaB
activation.
AB - Human T-cell leukemia virus type 1 (HTLV-1) Tax targets I-kappaB alpha and I
kappaB beta for phosphorylation, ubiquitination, and proteasome-mediated
degradation, causing the nuclear translocation of NF-kappaB/Rel proteins and
transcription induction of many cellular genes. The mechanism by which a nuclear
protein such as Tax stimulates I-kappaB phosphorylation and degradation remains
unclear. Here, we describe two cytoplasmic mutants of Tax, designated TaxDeltaN81
and TaxDeltaN109, from which the domains important for cyclic AMP response
element binding factor (CREB) and serum response factor (SRF) binding and nuclear
transport have been removed. These mutants were unable to trans activate from the
HTLV-1 21-bp repeats or the serum response element in the c-fos promoter. In
contrast, they activated NF-kappaB reporters, suggesting that activation of NF
kappaB by Tax occurs in the cytoplasm. Incorporation of the nuclear localization
signal (NLS) of the simian virus 40 large T antigen into TaxDeltaN81 and
TaxDeltaN109 redirected both proteins predominantly to the nucleus yet did not
restore trans activation via CREB or SRF. The NLS fusion had little effect on
TaxDeltaN81 but reduced NF-kappaB trans activation by TaxDeltaN109, possibly
because of its proximity to the NF-kappaB-activating domain of Tax. In contrast
to wild-type Tax, the cytoplasmic TaxDeltaN mutants are not cytotoxic. Stable
expression of TaxDeltaN109 in HeLa cells resulted in a significant reduction in
the intracellular level of I-kappaB alpha, with the constitutive presence of NF
kappaB in the nucleus and concomitant activation of the NF-kappaB enhancer. These
results are suggestive of a potential application of the TaxDeltaN109-like
mutants in targeting I-kappaB degradation and NF-kappaB activation.
Interestingly, a Tax species with a molecular mass similar to that of
TaxDeltaN109 was identified in many HTLV-1-transformed T cells, suggesting that
TaxDeltaN109-like species might play a role in HTLV-1-induced leukemogenesis.
PMID- 9658128
TI - Priming with tat-deleted caprine arthritis encephalitis virus (CAEV) proviral DNA
or live virus protects goats from challenge with pathogenic CAEV.
AB - We previously reported that infection of goats with caprine arthritis
encephalitis virus (CAEV) tat- proviral DNA or virus results in persistent
infection, since the animals seroconverted and direct virus isolation from
cultures of blood-derived macrophages was positive. In this study we wanted to
determine whether goats injected with CAEV tat- proviral DNA or virus were
protected against challenge with the pathogenic homologous virus and to
investigate whether CAEV tat- was still pathogenic. All animals injected with
CAEV tat- became infected as indicated by seroconversion and virus isolation.
Challenge at 8 or 9 months postinfection demonstrated protection in four of four
animals injected with CAEV tat- but did not in three of three mock-inoculated
challenged goats. Challenge virus was undetectable in the blood macrophages of
protected animals during a period of 6 or 10 months postchallenge. In two of four
protected animals, however, we were able to detect the challenge wild-type virus
by reverse transcriptase PCR on RNA directly extracted from synovial membrane
cells surrounding the inoculation site. This result suggests that protection was
achieved without complete sterilizing immunity. Animals injected with CAEV tat-
and mock challenged developed inflammatory lesions in the joints, although these
lesions were not as severe as those in CAEV wild-type-injected goats. These
results confirm the dispensable role of Tat in CAEV replication in vivo for the
establishment of infection and pathogenesis and demonstrate in another lentivirus
infection model the efficacy of live attenuated viruses to induce resistance to
superinfection.
PMID- 9658129
TI - Sequence requirements for removal of tRNA by an isolated human immunodeficiency
virus type 1 RNase H domain.
AB - Retroviral reverse transcriptase-associated RNase H enzymes are responsible for
degradation of viral RNA, including removal of the tRNA primer after plus-strand
strong-stop synthesis and cleavage of the polypurine tract primer. These
activities are required for the complex viral replication and result in
generation of the long terminal repeats. The human immunodeficiency virus type 1
(HIV-1) RNase H domain has been expressed independently of the polymerase domain
and possesses Mn2+-dependent activity with a hexahistidine tag. The isolated
domain maintains the ability to specifically remove a tRNA primer mimic. In this
study, the substrate determinants for recognition of the cognate tRNA3Lys are
defined. Model substrates were constructed which mimic the RNA-DNA hybrid
obtained from plus-strand strong-stop synthesis. Deletion substrates containing
only 12, 9, or 6 positions of the tRNA primer were capable of being cleaved by
the isolated RNase H domain. Mismatch and bromodeoxyuridine mutagenesis analysis
indicated that positions 2, 3, 4, and 6, when mutated, affected the specificity
of RNase H activity. Substitution substrates indicated that positions 4 and 6
within the RNA primer were important for recognition and cleavage by the HIV-1
isolated RNase H domain. Moloney murine leukemia virus-HIV-1 hybrid substrates
were constructed which demonstrated that changes to HIV-1 sequences at positions
4 and 6 were sufficient but not optimal for regaining cleavage by the isolated
HIV-1 RNase H domain. Optimal site-specific cleavage between the terminal
ribonucleotide A and ribonucleotide C requires additional sequences beyond the
first six positions but less than nine.
PMID- 9658130
TI - Overexpression of an alternatively spliced form of c-Myb results in increases in
transactivation and transforms avian myelomonoblasts.
AB - An alternatively spliced form of c-myb exists that encodes an additional 120
amino acids in chicken and 121 amino acids in human and mouse. These amino acids
are encoded by an additional exon, termed exon 9A. This exon is not present in v
myb, and proteins containing these amino acids have never been tested for
oncogenic transformation. A series of myb constructs was therefore created in
order to compare the functions of Myb proteins on the basis of their inclusion or
exclusion of the amino acids encoded by exon 9A (E9A). We found that the presence
of E9A resulted in a robust increase in transactivation for full-length c-Myb
(CCC), as well as the singly truncated derivatives dCC and CCd, while doubly
truncated Myb proteins v-Myb (dVd) and dCd did not exhibit any differences in
transactivation. The increase in transactivation requires the Myb DNA-binding
domain. When the leukemic transformation by the Myb proteins was tested, it was
found that cells transformed by dVd resembled monoblasts, while cells transformed
by CCC and its derivatives, dCd, dCC, and CCd, resembled myelomonoblasts. Despite
differences in the morphology of the hematopoietic cells, the cell surface
phenotypes and cell cycle profiles of transformed cells did not change for each
pair of Myb proteins in the presence or absence of E9A. Thus, there was no direct
correlation between the level of transcriptional activation and the strength of
leukemic transformation.
PMID- 9658131
TI - p53 protein is a suppressor of papillomavirus DNA amplificational replication.
AB - p53 protein was able to block human and bovine papillomavirus DNA amplificational
replication while not interfering with Epstein-Barr virus oriP once-per-cell
cycle replication. Oligomerization, intact DNA-binding, replication protein A
binding, and proline-rich domains of the p53 protein were essential for efficient
inhibition, while the N-terminal transcriptional activation and C-terminal
regulatory domains were dispensable for the suppressor activity of the p53
protein. The inhibition of replication was caused neither by the downregulation
of expression of the E1 and E2 proteins nor by cell cycle block or apoptosis. Our
data suggest that the intrinsic activity of p53 to suppress amplificational
replication of the papillomavirus origin may have an important role in the virus
life cycle and in virus-cell interactions.
PMID- 9658132
TI - Localization of varicella-zoster virus gene 21 protein in virus-infected cells in
culture.
AB - Although four varicella-zoster virus (VZV) genes have been shown to be
transcribed in latently infected human ganglia, their role in the development and
maintenance of latency is unknown. To study these VZV transcripts, we decided
first to localize their expression products in productively infected cells. We
began with VZV gene 21, whose open reading frame (ORF) is 3,113 bp. We cloned the
5' and 3' ends and the predicted antigenic segments of the ORF as 1292-, 1280-,
and 880-bp DNA fragments, respectively, into the prokaryotic expression vector
pGEX-2T. The three VZV 21 ORFs were expressed as approximately 75-, 73-, and 59
kDa glutathione S-transferase fusion proteins in Escherichia coli. To prepare
polyclonal antibodies that would recognize all potential epitopes on the VZV gene
21 protein, rabbits were inoculated with a mixture of the three fusion proteins,
and antisera were obtained and affinity purified. Immunohistochemical and
immunoelectron microscopic analyses using these antibodies revealed VZV ORF 21
protein in both the nucleus and cytoplasm of VZV-infected cells. When these
antibodies were applied to purified VZV nucleocapsids, intense staining was seen
in their central cores.
PMID- 9658133
TI - Coronavirus particle assembly: primary structure requirements of the membrane
protein.
AB - Coronavirus-like particles morphologically similar to normal virions are
assembled when genes encoding the viral membrane proteins M and E are coexpressed
in eukaryotic cells. Using this envelope assembly assay, we have studied the
primary sequence requirements for particle formation of the mouse hepatitis virus
(MHV) M protein, the major protein of the coronavirion membrane. Our results show
that each of the different domains of the protein is important. Mutations
(deletions, insertions, point mutations) in the luminal domain, the transmembrane
domains, the amphiphilic domain, or the carboxy-terminal domain had effects on
the assembly of M into enveloped particles. Strikingly, the extreme carboxy
terminal residue is crucial. Deletion of this single residue abolished particle
assembly almost completely; most substitutions were strongly inhibitory. Site
directed mutations in the carboxy terminus of M were also incorporated into the
MHV genome by targeted recombination. The results supported a critical role for
this domain of M in viral assembly, although the M carboxy terminus was more
tolerant of alteration in the complete virion than in virus-like particles,
likely because of the stabilization of virions by additional intermolecular
interactions. Interestingly, glycosylation of M appeared not essential for
assembly. Mutations in the luminal domain that abolished the normal O
glycosylation of the protein or created an N-glycosylated form had no effect.
Mutant M proteins unable to form virus-like particles were found to inhibit the
budding of assembly-competent M in a concentration-dependent manner. However,
assembly-competent M was able to rescue assembly-incompetent M when the latter
was present in low amounts. These observations support the existence of
interactions between M molecules that are thought to be the driving force in
coronavirus envelope assembly.
PMID- 9658134
TI - Kinetics of antiviral activity by human immunodeficiency virus type 1-specific
cytotoxic T lymphocytes (CTL) and rapid selection of CTL escape virus in vitro.
AB - The antiviral activity of a CD8(+) cytotoxic T-lymphocyte (CTL) clone (TCC108)
directed against a newly identified HLA-B14-restricted epitope, human
immunodeficiency virus type 1 (HIV-1) Rev(67-75) SAEPVPLQL, was analyzed with
respect to its kinetics of target cell lysis and inhibition of HIV-1 production.
Addition of TCC108 cells or CD8(+) reverse transcriptase-specific CTLs to HLA
matched CD4(+) T cells at different times after infection with HIV-1 IIIB showed
that infected cells became susceptible to CTL-mediated lysis before peak virus
production but after the onset of progeny virus release. When either of these
CTLs were added to part of the infected cells immediately after infection, p55
expression and virus production were significantly suppressed. These data support
a model in which CTLs, apart from exerting cytolytic activity which may prevent
continued virus release, can interfere with viral protein expression during the
eclipse phase via noncytolytic mechanisms. TCC108-mediated inhibition of virus
replication in peripheral blood mononuclear cells caused rapid selection of a
virus with a mutation (69E-->K) in the Rev(67-75) CTL epitope which abolished
recognition by TCC108 cells. Taken together, these data suggest that both
cytolytic and noncytolytic antiviral mechanisms of CTLs can be specifically
targeted to HIV-1-infected cells.
PMID- 9658135
TI - CXCR4 is required by a nonprimate lentivirus: heterologous expression of feline
immunodeficiency virus in human, rodent, and feline cells.
AB - A heterologous feline immunodeficiency virus (FIV) expression system permitted
high-level expression of FIV proteins and efficient production of infectious FIV
in human cells. These results identify the FIV U3 element as the sole restriction
to the productive phase of replication in nonfeline cells. Heterologous FIV
expression in a variety of human cell lines resulted in profuse syncytial lysis
that was FIV env specific, CD4 independent, and restricted to cells that express
CXCR4, the coreceptor for T-cell-line-adapted strains of human immunodeficiency
virus. Stable expression of human CXCR4 in CXCR4-negative human and rodent cell
lines resulted in extensive FIV Env-mediated, CXCR4-dependent cell fusion and
infection. In feline cells, stable overexpression of human CXCR4 resulted in
increased FIV infectivity and marked syncytium formation during FIV replication
or after infection with FIV Env-expressing vectors. The use of CXCR4 is a
fundamental feature of lentivirus biology independent of CD4 and a shared
cellular link to infection and cytopathicity for distantly related lentiviruses
that cause AIDS. Their conserved use implicates chemokine receptors as primordial
lentivirus receptors.
PMID- 9658137
TI - Circumvention of immunity to the adenovirus major coat protein hexon.
AB - Immunity to adenoviruses is an important hurdle to be overcome for successful
gene therapy. The presence of antibodies to the capsid proteins prevents
efficacious adenovirus vector administration in vivo. We tested whether immunity
to a particular serotype of adenovirus (Ad5) may be overcome with a vector that
encodes the hexon sequences from a different adenovirus serotype (Ad12). We
successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon
which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The
vector was also capable of transducing the livers of C57BL/6 mice previously
immunized with Ad5.
PMID- 9658136
TI - Infectious laryngotracheitis herpesvirus expresses a related pair of unique
nuclear proteins which are encoded by split genes located at the right end of the
UL genome region.
AB - Avian infectious laryngotracheitis virus (ILTV) possesses an alphaherpesvirus
type D DNA genome of ca. 155 kbp. Completion of our previous sequence analyses
(W. Fuchs and T. C. Mettenleiter, J. Gen. Virol. 77:2221-2229, 1996) of the right
end of the unique long (UL) genome region revealed the presence of two adjacent,
presumably ILTV-specific genes, which were named UL0 and UL[-1] because of their
location upstream of the conserved UL1 (glycoprotein L) gene. Transcriptional
analyses showed that both genes are abundantly expressed during the late phase of
the viral replication cycle and that both mRNAs are spliced by the removal of
short introns close to their 5' ends. Furthermore, the deduced gene products
exhibit a moderate but significant homology of 28% to each other. The newly
identified ILTV genes encode proteins of 63 kDa (UL0) and 73 kDa (UL[-1]), which
both are predominantly localized in the nuclei of virus infected chicken cells.
In summary, our results indicate that duplication of a spliced ILTV-specific gene
encoding a nuclear protein has occurred during evolution of ILTV.
PMID- 9658138
TI - A new vaccinia virus intermediate transcription factor.
AB - Transcription of the vaccinia virus genome is mediated by a virus-encoded
multisubunit DNA-dependent RNA polymerase in conjunction with early-,
intermediate-, and late-stage-specific factors. Previous studies indicated that
two virus-encoded proteins (capping enzyme and VITF-1) and one unidentified
cellular protein (VITF-2) are required for specific transcription of an
intermediate promoter template in vitro. We have now extensively purified an
additional virus-induced intermediate transcription factor with a native mass of
approximately 100 kDa.
PMID- 9658139
TI - Increased susceptibility of diabetic mice to influenza virus infection:
compromise of collectin-mediated host defense of the lung by glucose?
AB - The influence of diabetes on susceptibility to influenza virus infection was
examined in a mouse model in which RIP-Kb transgenic mice and their nontransgenic
littermates were used as the diabetic and nondiabetic hosts, respectively.
Influenza virus A/Phil/82 (H3N2) grew to significantly higher titers in the lungs
of diabetic than nondiabetic mice. The extent of viral replication in the lungs
was proportional to blood glucose levels in the mice at the time of infection,
and the enhanced susceptibility of diabetic mice was reversed with insulin.
Growth of A/HKx31 (H3N2) virus was also enhanced in diabetic mice, whereas the
highly virulent strain A/PR/8/34 (H1N1) showed no difference in virus yields in
diabetic and nondiabetic mice, even with low inocula. A/Phil/82 and A/HKx31 are
sensitive to neutralization in vitro by the pulmonary collectin surfactant
protein D (SP-D), whereas A/PR/8/34 is essentially resistant. Glucose is a ligand
for SP-D, and neutralization of A/Phil/82 virus by SP-D was abolished in the
presence of glucose at levels commonly found in diabetic mice. These findings
suggest that in mice, and perhaps in humans, diabetes predisposes to influenza
virus infection through compromise of collectin-mediated host defense of the lung
by glucose.
PMID- 9658140
TI - The probability of in vivo reactivation of herpes simplex virus type 1 increases
with the number of latently infected neurons in the ganglia.
AB - The purpose of this study was to define the relationship between herpes simplex
virus (HSV) latency and in vivo ganglionic reactivation. Groups of mice with
numbers of latently infected neurons ranging from 1.9 to 24% were generated by
varying the input titer of wild-type HSV type 1 strain 17syn+. Reactivation of
the virus in mice from each group was induced by hyperthermic stress. The number
of animals that exhibited virus reactivation was positively correlated with the
number of latently infected neurons in the ganglia over the entire range examined
(r = 0.9852, P < 0. 0001 [Pearson correlation]).
PMID- 9658141
TI - The papillomavirus E1 protein forms a DNA-dependent hexameric complex with ATPase
and DNA helicase activities.
AB - The E1 protein from bovine papillomavirus has site-specific DNA binding activity,
DNA helicase activity, and DNA-dependent ATPase activity consistent with the
properties of an initiator protein. Here we have identified and characterized a
novel oligomeric form of E1 that is associated with the ATPase and DNA helicase
activities and whose formation is strongly stimulated by single-stranded DNA.
This oligomeric form corresponds to a hexamer of E1.
PMID- 9658142
TI - Binding of murine leukemia virus Gag polyproteins to KIF4, a microtubule-based
motor protein.
AB - A cDNA clone encoding a cellular protein that interacts with murine leukemia
virus (MuLV) Gag proteins was isolated from a T-cell lymphoma library. The
sequence of the clone is identical to the C terminus of a cellular protein, KIF4,
a microtubule-associated motor protein that belongs to the kinesin superfamily.
KIF4-MuLV Gag associations have been detected in vitro and in vivo in mammalian
cells. We suggest that KIF4 could be involved in Gag polyprotein translocation
from the cytoplasm to the cell membrane.
PMID- 9658143
TI - Differential expression of Nur77 family members in human T-lymphotropic virus
type 1-infected cells: transactivation of the TR3/nur77 gene by Tax protein.
AB - We analyzed the differential expression and regulation of three members of the
Nur77 transcription factor family by the human T-lymphotropic virus type 1 (HTLV
1) Tax protein. We have demonstrated that in both HTLV-1-infected cells and Tax
expressing JPX-9 cells, TR3/nur77 is highly expressed, whereas neither NOR-1 nor
NOT expression is detectable. Transient transfection analysis further confirmed
the Tax transactivation of the TR3/nur77 promoter but not the NOR-1 promoter in
different cell types. Furthermore, expression of a luciferase reporter gene
driven by the NGFI-B (rat homolog of TR3/Nur77) response element (NBRE) provided
evidence that Tax-mediated transactivation resulted in the induction of a
functional protein. Cotransfection assays with the TR3/nur77 promoter sequence or
the NBRE binding motif together with a series of Tax mutants have shown that Tax
induced TR3/nur77 expression is mediated by CREB/ATF-related transcription
factors.
PMID- 9658144
TI - Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a
malaria parasite or of influenza virus elicit protection against the
corresponding pathogen in mice.
AB - Subcutaneous administration in mice of recombinant Sindbis viruses expressing a
class I major histocompatibility complex-restricted 9-mer epitope of the
Plasmodium yoelii circumsporozoite protein or the nucleoprotein of influenza
virus induces a large epitope-specific CD8(+) T-cell response. This immunization
also elicits a high degree of protection against infection with malaria or
influenza A virus.
PMID- 9658145
TI - Human immunodeficiency virus type 1 genome activation induced by human T-cell
leukemia virus type 1 Tax protein is through cooperation of NF-kappaB and Tat.
AB - For productive replication of human immunodeficiency virus type 1 (HIV-1) in host
cells, the viral genome-encoded transactivator Tat and several cellular
transcription factors are required for efficient viral gene transcription.
However, it remains unclear how the viral genome initiates transcription before
Tat is transcribed or when Tat is at suboptimal levels. Here, we utilized the
human T-cell leukemia type 1 Tax protein as a molecular tool to investigate the
mechanism of viral gene transcription that initiates the early phase of infection
of HIV-1. Tax alone does not significantly increase the activity of HIV-1 long
terminal repeat (LTR) in T lymphocytes, but it markedly enhanced the replication
of an infectious HIV-1 provirus with a truncated nef gene. This enhancement is
preferentially mediated by the cooperation of Tax and Tat which is dependent on
TAR and duplicated kappaB cis elements of the HIV-1 LTR as well as the NF-kappaB
activation domain of Tax. Furthermore, phorbol myristate acetate and membrane
targeted HIV-1 Nef also enhanced the LTR activity in the presence of Tat in the
TAR- and kappaB cis element-dependent manner. These data suggest that activated
NF-kappaB can functionally interact with a suboptimal amount of Tat and the HIV-1
LTR for efficient initiation of viral gene transcription.
PMID- 9658146
TI - Interleukin-12 p40 mRNA expression in bovine leukemia virus-infected animals:
increase in alymphocytosis but decrease in persistent lymphocytosis.
AB - Interleukin-12 (IL-12), a key cytokine in immune regulation, has an important
role in activating the cell-mediated immune response in infectious diseases.
Recently, a dichotomy between IL-12 and IL-10 regarding progression of a variety
diseases has emerged. IL-12 activates type 1 cytokine production and has an
antagonistic effect on type 2 cytokines. Here, by using quantitative competitive
PCR, we show that peripheral blood mononuclear cells from bovine leukemia virus
infected animals in the alymphocytotic stage of disease express an increased
amount of IL-12 p40 mRNA. In contrast, IL-12 p40 mRNA expression by cells from
animals with late-stage disease, termed persistent lymphocytosis, was
significantly decreased compared to that by normal and alymphocytotic animals.
Interestingly, IL-12 p40 mRNA was also detected in tumor-bearing animals. IL-12
p40 expression occurred only in monocytes/macrophages, not B or T lymphocytes.
The present study combined with previous findings suggest that IL-12 in bovine
leukemia virus-infected animals may regulate production of other cytokines such
as gamma interferon and IL-10 and the progression of bovine leukosis in animals
that develop more advanced disease such as a persistent lymphocytosis of B cells
or B-cell lymphosarcoma.
PMID- 9658147
TI - Antigenic structure of human respiratory syncytial virus fusion glycoprotein.
AB - New series of escape mutants of human respiratory syncytial virus were prepared
with monoclonal antibodies specific for the fusion (F) protein. Sequence changes
selected in the escape mutants identified two new antigenic sites (V and VI)
recognized by neutralizing antibodies and a group-specific site (I) in the F1
chain of the F molecule. The new epitopes, and previously identified antigenic
sites, were incorporated into a refined prediction of secondary-structure motifs
to generate a detailed antigenic map of the F glycoprotein.
PMID- 9658148
TI - Viral determinants of rotavirus pathogenicity in pigs: evidence that the fourth
gene of a porcine rotavirus confers diarrhea in the homologous host.
AB - A porcine rotavirus (prv) monoreassortant, S-F4, which carries RNA segment 4 of
the pig-pathogenic variant prv 4F in the genetic background of the pig
apathogenic variant prv 4S (G. I. Tauscher and U. Desselberger, J. Virol. 71:853
857, 1997), was found to be pathogenic in gnotobiotic piglets. This indicates
that RNA segment 4 of the pig-pathogenic variant prv 4F is a major determinant of
pathogenicity in its homologous host.
PMID- 9658149
TI - Apoptosis in feline panleukopenia virus-infected lymphocytes.
AB - Feline panleukopenia virus (FPLV) was shown to induce apoptosis to feline
lymphoid cells and to reduce the expression of interleukin-2 receptor alpha on
the cells. FPLV-induced apoptosis might be a key element in the pathophysiology
of atrophy of lymphoid tissues associated with feline panleukopenia caused by
FPLV.
PMID- 9658150
TI - Maintenance of an intact human immunodeficiency virus type 1 vpr gene following
mother-to-infant transmission.
AB - The vpr sequences from six human immunodeficiency virus type 1 (HIV-1)-infected
mother-infant pairs following perinatal transmission were analyzed. We found that
153 of the 166 clones analyzed from uncultured peripheral blood mononuclear cell
DNA samples showed a 92.17% frequency of intact vpr open reading frames. There
was a low degree of heterogeneity of vpr genes within mothers, within infants,
and between epidemiologically linked mother-infant pairs. The distances between
vpr sequences were greater in epidemiologically unlinked individuals than in
epidemiologically linked mother-infant pairs. Moreover, the infants' sequences
displayed patterns similar to those seen in their mothers. The functional domains
essential for Vpr activity, including virion incorporation, nuclear import, and
cell cycle arrest and differentiation were highly conserved in most of the
sequences. Phylogenetic analyses of 166 mother-infant pairs and 195 other
available vpr sequences from HIV databases formed distinct clusters for each
mother-infant pair and for other vpr sequences and grouped the six mother-infant
pairs' sequences with subtype B sequences. A high degree of conservation of
intact and functional vpr supports the notion that vpr plays an important role in
HIV-1 infection and replication in mother-infant isolates that are involved in
perinatal transmission.
PMID- 9658151
TI - Binding of the human immunodeficiency virus type 1 Gag protein to the viral RNA
encapsidation signal in the yeast three-hybrid system.
AB - We have used the yeast three-hybrid system (D. J. SenGupta, B. Zhang, B. Kraemer,
P. Pochart, S. Fields, and M. Wickens, Proc. Natl. Acad. Sci. USA 93:8496-8501,
1996) to study binding of the human immunodeficiency virus type 1 (HIV-1) Gag
protein to the HIV-1 RNA encapsidation signal (HIVPsi). Interaction of these
elements results in the activation of a reporter gene in the yeast Saccharomyces
cerevisiae. Using this system, we have shown that the HIV-1 Gag protein binds
specifically to a 139-nucleotide fragment of the HIVPsi signal containing four
stem-loop structures. Mutations in either the Gag protein or the encapsidation
signal that have been shown previously to impair this interaction reduced the
activation of the reporter gene. Interestingly, the nucleocapsid portion of Gag
retained the RNA binding activity but lost its specificity compared to the full
length Gag. These results demonstrate the utility of this system and suggest that
a variety of genetic analyses could be performed to study Gag-encapsidation
signal interactions.
PMID- 9658152
TI - Neutralizing antibodies in sera from macaques immunized with attenuated simian
immunodeficiency virus.
AB - Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques
has been shown to raise antibodies capable of neutralizing an animal challenge
stock of primary SIVmac251 in CEMx174 cells that correlate with resistance to
infection after experimental challenge with this virulent virus (M. S. Wyand, K.
H. Manson, M. Garcia-Moll, D. C. Montefiori, and R. C. Desrosiers, J. Virol.
70:3724-3733, 1996). Here we show that these neutralizing antibodies are not
detected in human and rhesus peripheral blood mononuclear cells (PBMC). In
addition, neutralization of primary SIVmac251 in human and rhesus PBMC was rarely
detected with plasma samples from a similar group of animals that had been
infected either with SIVmac239Deltanef for 1.5 years or with SIVmac239Delta3 for
3.2 years, although low-level neutralization was detected in CEMx174 cells.
Potent neutralization was detected in CEMx174 cells when the latter plasma
samples were assessed with laboratory-adapted SIVmac251. In contrast to primary
SIVmac251, laboratory-adapted SIVmac251 did not replicate in human and rhesus
PBMC despite its ability to utilize CCR5, Bonzo/STRL33, and BOB/gpr15 as
coreceptors for virus entry. These results illustrate the importance of virus
passage history and the choice of indicator cells for making assessments of
neutralizing antibodies to lentiviruses such as SIV. They also demonstrate that
primary SIVmac251 is less sensitive to neutralization in human and rhesus PBMC
than it is in established cell lines. Results obtained in PBMC did not support a
role for neutralizing antibodies as a mechanism of protection in animals
immunized with attenuated SIV and challenged with primary SIVmac251.
PMID- 9658153
TI - Ilarviruses encode a Cucumovirus-like 2b gene that is absent in other genera
within the Bromoviridae.
AB - We found that RNA 2 of the four ilarviruses sequenced to date encodes an
additional conserved open reading frame (ORF), 2b, that overlaps the 3' end of
the previously known ORF, 2a. A novel RNA species of 851 nucleotides was found to
accumulate to high levels in plants infected with spinach latent virus (SpLV).
Further analysis showed that RNA 4A is a subgenomic RNA of RNA 2 and encodes all
of ORF 2b. Moreover, a protein species of the size expected for SpLV ORF 2b was
translated in vitro from the RNA 4A-containing virion RNAs. The data support the
suggestion that the SpLV 2b protein is translated in vivo. The 2b gene of
ilarviruses, which is not encoded by alfamoviruses and bromoviruses, shares
several features with the previously reported cucumovirus 2b gene; however, their
encoded proteins share no detectable sequence similarities. The evolutionary
origin of the 2b gene is discussed.
PMID- 9658155
TI - Microtubule dynamics in mitotic spindle displayed by polarized light microscopy.
PMID- 9658154
TI - Production of uninfectious human immunodeficiency virus type 1 containing viral
protein R fused to a single-chain antibody against viral integrase.
AB - A single-chain antibody (scAb) against human immunodeficiency virus type 1 (HIV
1) integrase was expressed as a fusion protein of scAb and HIV-1 viral protein R
(Vpr), together with the HIV-1 genome, in human 293T cells. The expression did
not affect virion production much but markedly reduced the infectivity of progeny
virions. The fusion protein was found to be incorporated into the virions. The
incorporation appears to account for the reduced infectivity.
PMID- 9658156
TI - Imaging of echinoderm fertilization.
PMID- 9658157
TI - Self-centering in cytoplasmic fragments of melanophores.
PMID- 9658158
TI - Golgi membrane dynamics.
PMID- 9658159
TI - Nuclear and spindle dynamics in budding yeast.
PMID- 9658160
TI - Formation and turnover of NSF- and SNAP-containing "fusion" complexes occur on
undocked, clathrin-coated vesicle-derived membranes.
AB - Specificity of vesicular transport is determined by pair-wise interaction between
receptors (SNAP receptors or SNAREs) associated with a transport vesicle and its
target membrane. Two additional factors, N-ethylmaleimide-sensitive fusion
protein (NSF) and soluble NSF attachment protein (SNAP) are ubiquitous components
of vesicular transport pathways. However, the precise role they play is not
known. On the basis that NSF and SNAP can be recruited to preformed SNARE
complexes, it has been proposed that NSF- and SNAP-containing complexes are
formed after SNARE-dependent docking of transport vesicles. This would enable
ATPase-dependent complex disassembly to be coupled directly to membrane fusion.
Alternatively, binding and release of NSF/SNAP may occur before vesicle docking,
and perhaps be involved in the activation of SNAREs. To gain more information
about the point at which so-called 20S complexes form during the transport
vesicle cycle, we have examined NSF/SNAP/SNARE complex turnover on clathrin
coated vesicle-derived membranes in situ. This has been achieved under conditions
in which the extent of membrane docking can be precisely monitored. We
demonstrate by UV-dependent cross-linking experiments, coupled to laser light
scattering analysis of membranes, that complexes containing NSF, SNAP, and SNAREs
will form and dissociate on the surface of undocked transport vesicles.
PMID- 9658161
TI - A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a
mitochondrial targeting signal.
AB - Screening of a library derived from primary human endothelial cells revealed a
novel human isoform of vesicle-associated membrane protein-1 (VAMP-1), a protein
involved in the targeting and/or fusion of transport vesicles to their target
membrane. We have termed this novel isoform VAMP-1B and designated the previously
described isoform VAMP-1A. VAMP-1B appears to be an alternatively spliced form of
VAMP-1. A similar rat splice variant of VAMP-1 (also termed VAMP-1B) has recently
been reported. Five different cultured cell lines, from different lineages, all
contained VAMP-1B but little or no detectable VAMP-1A mRNA, as assessed by PCR.
In contrast, brain mRNA contained VAMP-1A but no VAMP-1B. The VAMP-1B sequence
encodes a protein identical to VAMP-1A except for the carboxy-terminal five amino
acids. VAMP-1 is anchored in the vesicle membrane by a carboxy-terminal
hydrophobic sequence. In VAMP-1A the hydrophobic anchor is followed by a single
threonine, which is the carboxy-terminal amino acid. In VAMP-1B the predicted
hydrophobic membrane anchor is shortened by four amino acids, and the hydrophobic
sequence is immediately followed by three charged amino acids, arginine-arginine
aspartic acid. Transfection of human endothelial cells with epitope-tagged VAMP
1B demonstrated that VAMP-1B was targeted to mitochondria whereas VAMP-1A was
localized to the plasma membrane and endosome-like structures. Analysis of C
terminal mutations of VAMP-1B demonstrated that mitochondrial targeting depends
both on the addition of positive charge at the C terminus and a shortened
hydrophobic membrane anchor. These data suggest that mitochondria may be
integrated, at least at a mechanistic level, to the vesicular trafficking
pathways that govern protein movement between other organelles of the cell.
PMID- 9658162
TI - Tyrosine phosphorylation of selected secretory carrier membrane proteins, SCAMP1
and SCAMP3, and association with the EGF receptor.
AB - Secretory carrier membrane proteins (SCAMPs) are ubiquitously expressed proteins
of post-Golgi vesicles. In the presence of the tyrosine phosphatase inhibitor
vanadate, or after overexpression in Chinese hamster ovary (CHO) cells, SCAMP1
and SCAMP3 are phosphorylated selectively on tyrosine residue(s). Phosphorylation
is reversible after vanadate washout in situ or when isolated SCAMP3 is incubated
with the recombinant tyrosine phosphatase PTP1B. Vanadate also causes the partial
accumulation of SCAMP3, but not SCAMP1, in "patches" at or near the cell surface.
A search for SCAMP kinase activities has shown that SCAMPs 1 and 3, but not
SCAMP2, are tyrosine phosphorylated in EGF-stimulated murine fibroblasts
overexpressing the EGF receptor (EGFR). EGF catalyzes the progressive
phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance
colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces
SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation
of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that
phosphorylation of SCAMPs, either directly or indirectly, may be functionally
linked to the internalization/down-regulation of the EGFR.
PMID- 9658163
TI - Expression of the recessive glomerulosclerosis gene Mpv17 regulates MMP-2
expression in fibroblasts, the kidney, and the inner ear of mice.
AB - The recessive mouse mutant Mpv17 is characterized by the development of early
onset glomerulosclerosis, concomitant hypertension, and structural alterations of
the inner ear. The primary cause of the disease is the loss of function of the
Mpv17 protein, a peroxisomal gene product involved in reactive oxygen metabolism.
In our search of a common mediator exerting effects on several aspects of the
phenotype, we discovered that the absence of the Mpv17 gene product causes a
strong increase in matrix metalloproteinase 2 (MMP-2) expression. This was seen
in the kidney and cochlea of Mpv17-negative mice as well as in tissue culture
cells derived from these animals. When these cells were transfected with the
human Mpv17 homolog, an inverse causal relationship between Mpv17 and MMP-2
expression was established. These results indicate that the Mpv17 protein plays a
crucial role in the regulation of MMP-2 and suggest that enhanced MMP-2
expression might mediate the mechanisms leading to glomerulosclerosis, inner ear
disease, and hypertension in this model.
PMID- 9658164
TI - An atypical sorting determinant in the cytoplasmic domain of P-selectin mediates
endosomal sorting.
AB - We previously identified the 11 amino acid C1 region of the cytoplasmic domain of
P-selectin as essential for an endosomal sorting event that confers rapid
turnover on P-selectin. The amino acid sequence of this region has no obvious
similarity to other known sorting motifs. We have analyzed the sequence
requirements for endosomal sorting by measuring the effects of site-specific
mutations on the turnover of P-selectin and of the chimeric protein LLP,
containing the lumenal and transmembrane domains of the low density lipoprotein
receptor and the cytoplasmic domain of P-selectin. Endosomal sorting activity was
remarkably tolerant of alanine substitutions within the C1 region. The activity
was eliminated by alanine substitution of only one amino acid residue, leucine
768, where substitution with several other large side chains, hydrophobic and
polar, maintained the sorting activity. The results indicate that the endosomal
sorting determinant is not structurally related to previously reported sorting
determinants. Rather, the results suggest that the structure of the sorting
determinant is dependent on the tertiary structure of the cytoplasmic domain.
PMID- 9658165
TI - A general RNA-binding protein complex that includes the cytoskeleton-associated
protein MAP 1A.
AB - Association of mRNA with the cytoskeleton represents a fundamental aspect of RNA
physiology likely involved in mRNA transport, anchoring, translation, and
turnover. We report the initial characterization of a protein complex that binds
RNA in a sequence-independent but size-dependent manner in vitro. The complex
includes a approximately 160-kDa protein that is bound directly to mRNA and that
appears to be either identical or highly related to a approximately 1600-kDa
protein that binds directly to mRNA in vivo. In addition, the microtubule
associated protein, MAP 1A, a cytoskeletal associated protein is a component of
this complex. We suggest that the general attachment of mRNA to the cytoskeleton
may be mediated, in part, through the formation of this ribonucleoprotein
complex.
PMID- 9658166
TI - Complex proteolytic processing acts on Delta, a transmembrane ligand for Notch,
during Drosophila development.
AB - Delta functions as a cell nonautonomous membrane-bound ligand that binds to
Notch, a cell-autonomous receptor, during cell fate specification. Interaction
between Delta and Notch leads to signal transduction and elicitation of cellular
responses. During our investigations to further understand the biochemical
mechanism by which Delta signaling is regulated, we have identified four Delta
isoforms in Drosophila embryonic and larval extracts. We have demonstrated that
at least one of the smaller isoforms, Delta S, results from proteolysis. Using
antibodies to the Delta extracellular and intracellular domains in colocalization
experiments, we have found that at least three Delta isoforms exist in vivo,
providing the first evidence that multiple forms of Delta exist during
development. Finally, we demonstrate that Delta is a transmembrane ligand that
can be taken up by Notch-expressing Drosophila cultured cells. Cell culture
experiments imply that full-length Delta is taken up by Notch-expressing cells.
We present evidence that suggests this uptake occurs by a nonphagocytic
mechanism.
PMID- 9658167
TI - Dominant negative alleles of SEC10 reveal distinct domains involved in secretion
and morphogenesis in yeast.
AB - The accurate targeting of secretory vesicles to distinct sites on the plasma
membrane is necessary to achieve polarized growth and to establish specialized
domains at the surface of eukaryotic cells. Members of a protein complex required
for exocytosis, the exocyst, have been localized to regions of active secretion
in the budding yeast Saccharomyces cerevisiae where they may function to specify
sites on the plasma membrane for vesicle docking and fusion. In this study we
have addressed the function of one member of the exocyst complex, Sec10p. We have
identified two functional domains of Sec10p that act in a dominant-negative
manner to inhibit cell growth upon overexpression. Phenotypic and biochemical
analysis of the dominant-negative mutants points to a bifunctional role for
Sec10p. One domain, consisting of the amino-terminal two-thirds of Sec10p
directly interacts with Sec15p, another exocyst component. Overexpression of this
domain displaces the full-length Sec10 from the exocyst complex, resulting in a
block in exocytosis and an accumulation of secretory vesicles. The carboxy
terminal domain of Sec10p does not interact with other members of the exocyst
complex and expression of this domain does not cause a secretory defect. Rather,
this mutant results in the formation of elongated cells, suggesting that the
second domain of Sec10p is required for morphogenesis, perhaps regulating the
reorientation of the secretory pathway from the tip of the emerging daughter cell
toward the mother-daughter connection during cell cycle progression.
PMID- 9658168
TI - The yeast dynactin complex is involved in partitioning the mitotic spindle
between mother and daughter cells during anaphase B.
AB - Although vertebrate cytoplasmic dynein can move to the minus ends of microtubules
in vitro, its ability to translocate purified vesicles on microtubules depends on
the presence of an accessory complex known as dynactin. We have cloned and
characterized a novel gene, NIP100, which encodes the yeast homologue of the
vertebrate dynactin complex protein p150(glued). Like strains lacking the
cytoplasmic dynein heavy chain Dyn1p or the centractin homologue Act5p,
nip100Delta strains are viable but undergo a significant number of failed mitoses
in which the mitotic spindle does not properly partition into the daughter cell.
Analysis of spindle dynamics by time-lapse digital microscopy indicates that the
precise role of Nip100p during anaphase is to promote the translocation of the
partially elongated mitotic spindle through the bud neck. Consistent with the
presence of a true dynactin complex in yeast, Nip100p exists in a stable complex
with Act5p as well as Jnm1p, another protein required for proper spindle
partitioning during anaphase. Moreover, genetic depletion experiments indicate
that the binding of Nip100p to Act5p is dependent on the presence of Jnm1p.
Finally, we find that a fusion of Nip100p to the green fluorescent protein
localizes to the spindle poles throughout the cell cycle. Taken together, these
results suggest that the yeast dynactin complex and cytoplasmic dynein together
define a physiological pathway that is responsible for spindle translocation late
in anaphase.
PMID- 9658169
TI - Identification of novel temperature-sensitive lethal alleles in essential beta
tubulin and nonessential alpha 2-tubulin genes as fission yeast polarity mutants.
AB - We have screened for temperature-sensitive (ts) fission yeast mutants with
altered polarity (alp1-15). Genetic analysis indicates that alp2 is allelic to
atb2 (one of two alpha-tubulin genes) and alp12 to nda3 (the single beta-tubulin
gene). atb2(+) is nonessential, and the ts atb2 mutations we have isolated are
dominant as expected. We sequenced two alleles of ts atb2 and one allele of ts
nda3. In the ts atb2 mutants, the mutated residues (G246D and C356Y) are found at
the longitudinal interface between alpha/beta-heterodimers, whereas in ts nda3
the mutated residue (Y422H) is situated in the domain located on the outer
surface of the microtubule. The ts nda3 mutant is highly sensitive to altered
gene dosage of atb2(+); overexpression of atb2(+) lowers the restrictive
temperature, and, conversely, deletion rescues ts. Phenotypic analysis shows that
contrary to undergoing mitotic arrest with high viability via the spindle
assembly checkpoint as expected, ts nda3 mutants execute cytokinesis and
septation and lose viability. Therefore, it appears that the ts nda3 mutant
becomes temperature lethal because of irreversible progression through the cell
cycle in the absence of activating the spindle assembly checkpoint pathway.
PMID- 9658170
TI - Localization of autocrine motility factor receptor to caveolae and clathrin
independent internalization of its ligand to smooth endoplasmic reticulum.
AB - Autocrine motility factor receptor (AMF-R) is a cell surface receptor that is
also localized to a smooth subdomain of the endoplasmic reticulum, the AMF-R
tubule. By postembedding immunoelectron microscopy, AMF-R concentrates within
smooth plasmalemmal vesicles or caveolae in both NIH-3T3 fibroblasts and HeLa
cells. By confocal microscopy, cell surface AMF-R labeled by the addition of anti
AMF-R antibody to viable cells at 4 degreesC exhibits partial colocalization with
caveolin, confirming the localization of cell surface AMF-R to caveolae. Labeling
of cell surface AMF-R by either anti-AMF-R antibody or biotinylated AMF (bAMF)
exhibits extensive colocalization and after a pulse of 1-2 h at 37 degreesC, bAMF
accumulates in densely labeled perinuclear structures as well as fainter tubular
structures that colocalize with AMF-R tubules. After a subsequent 2- to 4-h
chase, bAMF is localized predominantly to AMF-R tubules. Cytoplasmic
acidification, blocking clathrin-mediated endocytosis, results in the essentially
exclusive distribution of internalized bAMF to AMF-R tubules. By confocal
microscopy, the tubular structures labeled by internalized bAMF show complete
colocalization with AMF-R tubules. bAMF internalized in the presence of a 10-fold
excess of unlabeled AMF labels perinuclear punctate structures, which are
therefore the product of fluid phase endocytosis, but does not label AMF-R
tubules, demonstrating that bAMF targeting to AMF-R tubules occurs via a receptor
mediated pathway. By electron microscopy, bAMF internalized for 10 min is located
to cell surface caveolae and after 30 min is present within smooth and rough
endoplasmic reticulum tubules. AMF-R is therefore internalized via a receptor
mediated clathrin-independent pathway to smooth ER. The steady state localization
of AMF-R to caveolae implicates these cell surface invaginations in AMF-R
endocytosis.
PMID- 9658171
TI - Role of tyrosine phosphorylation in ligand-induced regulation of transcytosis of
the polymeric Ig receptor.
AB - The polymeric Ig receptor (pIgR) transcytoses its ligand, dimeric IgA (dIgA),
from the basolateral to the apical surface of epithelial cells. Although the pIgR
is constitutively transcytosed in the absence of ligand, binding of dIgA
stimulates transcytosis of the pIgR. We recently reported that dIgA binding to
the pIgR induces translocation of protein kinase C, production of inositol
triphosphate, and elevation of intracellular free calcium. We now report that
dIgA binding causes rapid, transient tyrosine phosphorylation of several
proteins, including phosphatidyl inositol-specific phospholipase C-gammal.
Protein tyrosine kinase inhibitors or deletion of the last 30 amino acids of pIgR
cytoplasmic tail prevents IgA-stimulated protein tyrosine kinase activation,
tyrosine phosphorylation of phospholipase C-gammal, production of inositol
triphosphate, and the stimulation of transcytosis by dIgA. Analysis of pIgR
deletion mutants reveals that the same discrete portion of the cytoplasmic
domain, residues 727-736 (but not the Tyr734), controls both the ability of pIgR
to cause dIgA-induced tyrosine phosphorylation of the phospholipase C-gammal and
to undergo dIgA-stimulated transcytosis. In addition, dIgA transcytosis can be
strongly stimulated by mimicking phospholipase C-gammal activation. In
combination with our previous results, we conclude that the protein tyrosine
kinase(s) and phospholipase C-gammal that are activated upon dIgA binding to the
pIgR control dIgA-stimulated pIgR transcytosis.
PMID- 9658172
TI - Serine and threonine phosphorylation of the paxillin LIM domains regulates
paxillin focal adhesion localization and cell adhesion to fibronectin.
AB - We have previously shown that the LIM domains of paxillin operate as the focal
adhesion (FA)-targeting motif of this protein. In the current study, we have
identified the capacity of paxillin LIM2 and LIM3 to serve as binding sites for,
and substrates of serine/threonine kinases. The activities of the LIM2- and LIM3
associated kinases were stimulated after adhesion of CHO.K1 cells to fibronectin;
consequently, a role for LIM domain phosphorylation in regulating the subcellular
localization of paxillin after adhesion to fibronectin was investigated. An avian
paxillin-CHO.K1 model system was used to explore the role of paxillin
phosphorylation in paxillin localization to FAs. We found that mutations of
paxillin that mimicked LIM domain phosphorylation accelerated fibronectin-induced
localization of paxillin to focal contacts. Further, blocking phosphorylation of
the LIM domains reduced cell adhesion to fibronectin, whereas constitutive LIM
domain phosphorylation significantly increased the capacity of cells to adhere to
fibronectin. The potentiation of FA targeting and cell adhesion to fibronectin
was specific to LIM domain phosphorylation as mutation of the amino-terminal
tyrosine and serine residues of paxillin that are phosphorylated in response to
fibronectin adhesion had no effect on the rate of FA localization or cell
adhesion. This represents the first demonstration of the regulation of protein
localization through LIM domain phosphorylation and suggests a novel mechanism of
regulating LIM domain function. Additionally, these results provide the first
evidence that paxillin contributes to "inside-out" integrin-mediated signal
transduction.
PMID- 9658173
TI - Regulation of the cyclin B degradation system by an inhibitor of mitotic
proteolysis.
AB - The initiation of anaphase and exit from mitosis depend on the anaphase-promoting
complex (APC), which mediates the ubiquitin-dependent proteolysis of anaphase
inhibiting proteins and mitotic cyclins. We have analyzed whether protein
phosphatases are required for mitotic APC activation. In Xenopus egg extracts APC
activation occurs normally in the presence of protein phosphatase 1 inhibitors,
suggesting that the anaphase defects caused by protein phosphatase 1 mutation in
several organisms are not due to a failure to activate the APC. Contrary to this,
the initiation of mitotic cyclin B proteolysis is prevented by inhibitors of
protein phosphatase 2A such as okadaic acid. Okadaic acid induces an activity
that inhibits cyclin B ubiquitination. We refer to this activity as inhibitor of
mitotic proteolysis because it also prevents the degradation of other APC
substrates. A similar activity exists in extracts of Xenopus eggs that are
arrested at the second meiotic metaphase by the cytostatic factor activity of the
protein kinase mos. In Xenopus eggs, the initiation of anaphase II may therefore
be prevented by an inhibitor of APC-dependent ubiquitination.
PMID- 9658174
TI - Multiple domains of fission yeast Cdc19p (MCM2) are required for its association
with the core MCM complex.
AB - The members of the MCM protein family are essential eukaryotic DNA replication
factors that form a six-member protein complex. In this study, we use antibodies
to four MCM proteins to investigate the structure of and requirements for the
formation of fission yeast MCM complexes in vivo, with particular regard to
Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are
unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we
find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another
in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with
the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p
containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants,
we find that multiple domains of Cdc19p are required for MCM binding. These
studies indicate that MCM complexes in fission yeast have distinct substructures,
which may be relevant for function.
PMID- 9658175
TI - Katanin is responsible for the M-phase microtubule-severing activity in Xenopus
eggs.
AB - Microtubules are dynamic structures whose proper rearrangement during the cell
cycle is essential for the positioning of membranes during interphase and for
chromosome segregation during mitosis. The previous discovery of a cyclin B/cdc2
activated microtubule-severing activity in M-phase Xenopus egg extracts suggested
that a microtubule-severing protein might play an important role in cell cycle
dependent changes in microtubule dynamics and organization. However, the
isolation of three different microtubule-severing proteins, p56, EF1alpha, and
katanin, has only confused the issue because none of these proteins is directly
activated by cyclin B/cdc2. Here we use immunodepletion with antibodies specific
for a vertebrate katanin homologue to demonstrate that katanin is responsible for
the majority of M-phase severing activity in Xenopus eggs. This result suggests
that katanin is responsible for changes in microtubules occurring at mitosis.
Immunofluorescence analysis demonstrated that katanin is concentrated at a
microtubule-dependent structure at mitotic spindle poles in Xenopus A6 cells and
in human fibroblasts, suggesting a specific role in microtubule disassembly at
spindle poles. Surprisingly, katanin was also found in adult mouse brain,
indicating that katanin may have other functions distinct from its mitotic role.
PMID- 9658176
TI - Activation of Rac and Cdc42 by integrins mediates cell spreading.
AB - Adhesion to ECM is required for many cell functions including cytoskeletal
organization, migration, and proliferation. We observed that when cells first
adhere to extracellular matrix, they spread rapidly by extending filopodia-like
projections and lamellipodia. These structures are similar to the Rac- and Cdc42
dependent structures observed in growth factor-stimulated cells. We therefore
investigated the involvement of Rac and Cdc42 in adhesion and spreading on the
ECM protein fibronectin. We found that integrin-dependent adhesion led to the
rapid activation of p21-activated kinase, a downstream effector of Cdc42 and Rac,
suggesting that integrins activate at least one of these GTPases. Dominant
negative mutants of Rac and Cdc42 inhibit cell spreading in such a way as to
suggest that integrins activate Cdc42, which leads to the subsequent activation
of Rac; both GTPases then contribute to cell spreading. These results demonstrate
that initial integrin-dependent activation of Rac and Cdc42 mediates cell
spreading.
PMID- 9658177
TI - Multiple functions for actin during filamentous growth of Saccharomyces
cerevisiae.
AB - Saccharomyces cerevisiae is dimorphic and switches from a yeast form to a
pseudohyphal (PH) form when starved for nitrogen. PH cells are elongated, bud in
a unipolar manner, and invade the agar substrate. We assessed the requirements
for actin in mediating the dramatic morphogenetic events that accompany the
transition to PH growth. Twelve "alanine scan" alleles of the single yeast actin
gene (ACT1) were tested for effects on filamentation, unipolar budding, agar
invasion, and cell elongation. Some act1 mutations affect all phenotypes, whereas
others affect only one or two aspects of PH growth. Tests of intragenic
complementation among specific act1 mutations support the phenotypic evidence for
multiple actin functions in filamentous growth. We present evidence that
interaction between actin and the actin-binding protein fimbrin is important for
PH growth and suggest that association of different actin-binding proteins with
actin mediates the multiple functions of actin in filamentous growth.
Furthermore, characterization of cytoskeletal structure in wild type and
act1/act1 mutants indicates that PH cell morphogenesis requires the maintenance
of a highly polarized actin cytoskeleton. Collectively, this work demonstrates
that actin plays a central role in fungal dimorphism.
PMID- 9658178
TI - RhoA GTPase and serum response factor control selectively the expression of MyoD
without affecting Myf5 in mouse myoblasts.
AB - MyoD and Myf5 belong to the family of basic helix-loop-helix transcription
factors that are key operators in skeletal muscle differentiation. MyoD and Myf5
genes are selectively activated during development in a time and region-specific
manner and in response to different stimuli. However, molecules that specifically
regulate the expression of these two genes and the pathways involved remain to be
determined. We have recently shown that the serum response factor (SRF), a
transcription factor involved in activation of both mitogenic response and muscle
differentiation, is required for MyoD gene expression. We have investigated here
whether SRF is also involved in the control of Myf5 gene expression, and the
potential role of upstream regulators of SRF activity, the Rho family G-proteins
including Rho, Rac, and CDC42, in the regulation of MyoD and Myf5. We show that
inactivation of SRF does not alter Myf5 gene expression, whereas it causes a
rapid extinction of MyoD gene expression. Furthermore, we show that RhoA, but not
Rac or CDC42, is also required for the expression of MyoD. Indeed, blocking the
activity of G-proteins using the general inhibitor lovastatin, or more specific
antagonists of Rho proteins such as C3-transferase or dominant negative RhoA
protein, resulted in a dramatic decrease of MyoD protein levels and promoter
activity without any effects on Myf5 expression. We further show that RhoA
dependent transcriptional activation required functional SRF in C2 muscle cells.
These data illustrate that MyoD and Myf5 are regulated by different upstream
activation pathways in which MyoD expression is specifically modulated by a
RhoA/SRF signaling cascade. In addition, our results establish the first link
between RhoA protein activity and the expression of a key muscle regulator.
PMID- 9658179
TI - Osteoblastic responses to TGF-beta during bone remodeling.
AB - Bone remodeling depends on the spatial and temporal coupling of bone formation by
osteoblasts and bone resorption by osteoclasts; however, the molecular basis of
these inductive interactions is unknown. We have previously shown that
osteoblastic overexpression of TGF-beta2 in transgenic mice deregulates bone
remodeling and leads to an age-dependent loss of bone mass that resembles high
turnover osteoporosis in humans. This phenotype implicates TGF-beta2 as a
physiological regulator of bone remodeling and raises the question of how this
single secreted factor regulates the functions of osteoblasts and osteoclasts and
coordinates their opposing activities in vivo. To gain insight into the
physiological role of TGF-beta in bone remodeling, we have now characterized the
responses of osteoblasts to TGF-beta in these transgenic mice. We took advantage
of the ability of alendronate to specifically inhibit bone resorption, the lack
of osteoclast activity in c-fos-/- mice, and a new transgenic mouse line that
expresses a dominant-negative form of the type II TGF-beta receptor in
osteoblasts. Our results show that TGF-beta directly increases the steady-state
rate of osteoblastic differentiation from osteoprogenitor cell to terminally
differentiated osteocyte and thereby increases the final density of osteocytes
embedded within bone matrix. Mice overexpressing TGF-beta2 also have increased
rates of bone matrix formation; however, this activity does not result from a
direct effect of TGF-beta on osteoblasts, but is more likely a homeostatic
response to the increase in bone resorption caused by TGF-beta. Lastly, we find
that osteoclastic activity contributes to the TGF-beta-induced increase in
osteoblast differentiation at sites of bone resorption. These results suggest
that TGF-beta is a physiological regulator of osteoblast differentiation and acts
as a central component of the coupling of bone formation to resorption during
bone remodeling.
PMID- 9658180
TI - Isolation and contraction of the stress fiber.
AB - Stress fibers were isolated from cultured human foreskin fibroblasts and bovine
endothelial cells, and their contraction was demonstrated in vitro. Cells in
culture dishes were first treated with a low-ionic-strength extraction solution
and then further extracted using detergents. With gentle washes by pipetting, the
nucleus and the apical part of cells were removed. The material on the culture
dish was scraped, and the freed material was forced through a hypodermic needle
and fractionated by sucrose gradient centrifugation. Isolated, free-floating
stress fibers stained brightly with fluorescently labeled phalloidin. When
stained with anti-alpha-actinin or anti-myosin, isolated stress fibers showed
banded staining patterns. By electron microscopy, they consisted of bundles of
microfilaments, and electron-dense areas were associated with them in a
semiperiodic manner. By negative staining, isolated stress fibers often exhibited
gentle twisting of microfilament bundles. Focal adhesion-associated proteins were
also detected in the isolated stress fiber by both immunocytochemical and
biochemical means. In the presence of Mg-ATP, isolated stress fibers shortened,
on the average, to 23% of the initial length. The maximum velocity of shortening
was several micrometers per second. Polystyrene beads on shortening isolated
stress fibers rotated, indicating spiral contraction of stress fibers. Myosin
regulatory light chain phosphorylation was detected in contracting stress fibers,
and a myosin light chain kinase inhibitor, KT5926, inhibited isolated stress
fiber contraction. Our study demonstrates that stress fibers can be isolated with
no apparent loss of morphological features and that they are truly contractile
organelle.
PMID- 9658182
TI - Editorial
PMID- 9658181
TI - Actin filaments and microtubules are involved in different membrane traffic
pathways that transport sphingolipids to the apical surface of polarized HepG2
cells.
AB - In polarized HepG2 hepatoma cells, sphingolipids are transported to the apical,
bile canalicular membrane by two different transport routes, as revealed with
fluorescently tagged sphingolipid analogs. One route involves direct,
transcytosis-independent transport of Golgi-derived glucosylceramide and
sphingomyelin, whereas the other involves basolateral to apical transcytosis of
both sphingolipids. We show that these distinct routes display a different
sensitivity toward nocodazole and cytochalasin D, implying a specific transport
dependence on either microtubules or actin filaments, respectively. Thus,
nocodazole strongly inhibited the direct route, whereas sphingolipid transport by
transcytosis was hardly affected. Moreover, nocodazole blocked
"hyperpolarization," i.e., the enlargement of the apical membrane surface, which
is induced by treating cells with dibutyryl-cAMP. By contrast, the transcytotic
route but not the direct route was inhibited by cytochalasin D. The actin
dependent step during transcytotic lipid transport probably occurs at an early
endocytic event at the basolateral plasma membrane, because total lipid uptake
and fluid phase endocytosis of horseradish peroxidase from this membrane were
inhibited by cytochalasin D as well. In summary, the results show that the two
sphingolipid transport pathways to the apical membrane must have a different
requirement for cytoskeletal elements.
PMID- 9658183
TI - J-104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in
vivo in a farnesyl pyrophosphate-competitive manner.
AB - Farnesylation of the activated ras oncogene product by protein
farnesyltransferase (FTase) is a critical step for its oncogenic function.
Because squalene synthase and FTase recruit farnesyl pyrophosphate as a common
substrate, we modified squalene synthase (SS) inhibitors to develop FTase
inhibitors. Among the compounds tested, a novel FTase inhibitor termed J-104,871
inhibited rat brain FTase with an IC50 of 3.9 nM in the presence of 0.6 microM
farnesyl pyrophosphate (FPP), whereas it scarcely inhibited rat brain protein
geranylgeranyltransferase-I or SS. The in vitro inhibition of rat brain FTase by
J-104,871 depends on the FPP concentration but not on the concentration of Ras
peptide. Thus, in vitro studies strongly suggest that J-series compounds have an
FPP-competitive nature. J-104,871 also inhibited Ras processing in activated H
ras-transformed NIH3T3 cells with an IC50 value of 3.1 microM. We tested the
effects of lovastatin and zaragozic acid A, which modify cellular FPP levels, on
Ras processing of J-104,871. Lovastatin, a hepatic hydroxymenthyl coenzyme A
reductase inhibitor that reduced the cellular FPP pool, increased the activity of
J-104,871, whereas 3 microM zaragozic acid A, an SS inhibitor that raised the FPP
level, completely abrogated the activity of J-104,871 even at 100 microM. These
results suggest that J-104,871 inhibits FTase in an FPP-competitive manner in
whole cells as well as in the in vitro system. Furthermore, J-104,871 suppressed
tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3
cells.
PMID- 9658184
TI - Yeast expressed cytochrome P450 2D6 (CYP2D6) exposed on the external face of
plasma membrane is functionally competent.
AB - CYP2D6, a xenobiotic metabolizing cytochrome P450 (P450), was found to be present
in significant amount on the outer face of cell plasma membrane in addition to
the regular microsomal location. Present work demonstrates that this external
P450 is catalytically competent and that activity is supported by NADPH-P450
reductase present on the inner face of plasma membrane. Purified plasma membranes
from yeast expressing CYP2D6 sustained NADPH- and cumene hydroperoxide-dependent
dextromethorphan demethylation and NADPH-cytochrome c activity confirming
previous observations in human hepatocytes. CYP2D6 found on the outside of plasma
membrane (by differential immuno-inhibition and acidic shift assays on
transformed spheroplasts) was catalytically competent at the cell surface for
NADPH-supported activities. Anti-yeast P450-reductase antibodies inhibited
neither CYP2D6 nor P450-reductase activities upon incubation with intact
spheroplasts. In contrast, both activities were inhibited on isolated plasma
membrane fragments. This highly suggested a cytosolic-orientation of the plasma
membrane P450-reductase. This finding was confirmed by immunostaining in confocal
microscopy. Finally, gene deletion of P450-reductase caused a complete loss of
plasma membrane NADPH-supported CYP2D6 activity, which suggests that the
reductase participates to some degree in the transmembrane electron transfer
chain. This work illustrates that the outside-exposed plasma membrane CYP2D6 is
active and may play an important metabolic role.
PMID- 9658185
TI - Protein kinase C-mediated down-regulation of beta1-adrenergic receptor gene
expression in rat C6 glioma cells.
AB - In the current study, we investigated the mechanism by which protein kinase C
(PKC) regulates the expression of beta1-adrenergic receptor (beta1AR) mRNA in rat
C6 glioma cells. Exposure of the cells to 4beta-phorbol-12-myristate-13-acetate
(PMA), an activator PKC, resulted in a down-regulation of both beta1AR binding
sites and mRNA levels in a time- and concentration-dependent manner. This effect
was not observed with phorbol esters that do not activate PKC and was blocked by
bisindolylmaleimide, a specific PKC inhibitor. Activation of PKC did not reduce
the half-life of beta1AR mRNA but significantly decreased the activity of the
beta1AR promoter, as determined by reporter analysis. A putative response
element, with partial homology to a consensus cAMP response element, was
identified by mutation analysis of the promoter at positions -343 to -336,
relative to the translational start site. Mutation of this putative regulatory
element, referred to as a beta1AR-PKC response element, completely blocked the
PKC-mediated down-regulation of beta1AR promoter activity. Gel mobility shift
analysis detected two specific bands when C6 cell extracts were incubated with a
labeled DNA probe containing the beta1AR-PKC response element sequence. Formation
of one of these bands was inhibited by an oligonucleotide probe containing a
consensus CRE and disrupted by an antibody for cAMP response element binding
protein. Based on these studies, we propose that the PKC-induced down-regulation
of beta1AR gene transcription in C6 cells is mediated in part by a cAMP response
element binding protein-dependent mechanism acting on a novel response element.
PMID- 9658186
TI - Isoquinolines as antagonists of the P2X7 nucleotide receptor: high selectivity
for the human versus rat receptor homologues.
AB - 1-[N, O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN
62) and N-[1-[N-methyl-p-(5 isoquinolinesulfonyl)benzyl]-2-(4
phenylpiperazine)ethyl]-5-isoquinolinesulfonamide (KN-04) potently inhibit the
human lymphocyte P2Z receptor, an ATP-gated cation channel [Br J Pharmacol
120:1483-1490 (1997)]. Although the molecular identity of the lymphocyte P2Z
receptor has not been established, it shares many functional characteristics with
the cloned P2X7 nucleotide receptor. We have tested whether these isoquinolines
inhibit P2X receptor function in human embryonic kidney 293 cells that stably
express the human or rat recombinant P2X7 receptors. ATP activation of cation
currents and uptake of the organic dye ethidium were potently inhibited by KN-62
and KN-04 in human embryonic kidney cells expressing the human P2X7R but not the
rat P2X7R, even though these species homologues share 80% amino acid identity.
Introduction of the first 335 amino acids of the human P2X7R sequence conferred
KN-62 sensitivity to the rat P2X7R; this suggests that isoquinolines interact
with residues in the amino-terminal half (containing the large extracellular
loop) of the human P2X7R. KN-62 and KN-04 also potently inhibited ATP-gated Ca2+
influx and ethidium uptake in several leukocyte cell lines (THP-1, BAC1.2f5, and
BW5147) that natively express the human or murine P2X7R mRNA. The ability of
isoquinoline sulfonamides to potently inhibit human and murine P2X7R signaling
will be a useful tool for identifying P2Z/P2X7 functional responses in other cell
types. The substantial differences in pharmacological sensitivity between rat and
human P2X7R may also indicate structural domains important in channel/pore
activation.
PMID- 9658187
TI - Photoaffinity labeling of the benzodiazepine binding site of alpha1beta3gamma2
gamma-aminobutyric acidA receptors with flunitrazepam identifies a subset of
ligands that interact directly with His102 of the alpha subunit and predicts
orientation of these within the benzodiazepine pharmacophore.
AB - Photoincorporation of ligands into the benzodiazepine site of native gamma
aminobutyric acidA (GABAA) receptors provides useful information about the nature
of the benzodiazepine (BZ) binding site. Photoincorporation of flunitrazepam into
a single population of GABAA receptors, recombinant human alpha1beta3gamma2, was
investigated to probe further the mechanism and orientation of flunitrazepam and
other ligands in the BZ binding site. It was concluded that the receptor is
primarily derivatized with the entire, unfragmented, flunitrazepam molecule,
which undergoes a conformational change during photolysis and largely vacates the
benzodiazepine binding site. Investigation of the BZ site after
photoincorporation of [3H]flunitrazepam confirmed that binding of other
radioligands was unaffected by incorporation of flunitrazepam. This did not
correlate with their efficacy but depended on the presence of particular
structural features in the molecule. It was observed that affected compounds have
a pendant phenyl moiety, analogous to the 5-phenyl group of flunitrazepam, which
are proposed to overlap and interact with the same residue or residues in the BZ
binding site. Because the major site of flunitrazepam photoincorporation has been
shown to be His102, we propose that this group of compounds interacts directly
with His 102, whereas compounds of other structural types have no direct
interaction with this amino acid. The orientation of ligands within the BZ
binding site and their specific interaction with identified amino acids are not
well understood. The data in the current study indicate that His102 interacts
directly with the pendant phenyl group of diazepam, and further implications for
the pharmacophore of the BZ binding site are discussed.
PMID- 9658188
TI - Phosphorylation and functional desensitization of the alpha2A-adrenergic receptor
by protein kinase C.
AB - We have investigated the potential for protein kinase C (PKC) to phosphorylate
and desensitize the alpha2A-adrenergic receptor (alpha2AAR). In whole-cell
phosphorylation studies, recombinantly expressed human alpha2AAR displayed an
increase in phosphorylation after short-term exposure to 100 nM phorbol 12
myristate-13-acetate (PMA) that was blocked by preincubation with a PKC
inhibitor. This increase in receptor phosphorylation over basal amounted to 172
+/- 40% in COS-7 cells and 201 +/- 40% in Chinese hamster ovary cells. In
permanently transfected Chinese hamster fibroblast cells, PKC activation by brief
exposure of the cells to PMA resulted in a marked desensitization of alpha2AAR
function, amounting to a 68 +/- 4% decrease in the maximal agonist (UK14304)
stimulated intracellular calcium release. Such desensitization was blocked by the
PKC inhibitor bisindolylmaleimide I and was not evoked by an inactive phorbol
ester. The desensitization of this agonist response was not caused by PKC
mediated augmentation of G protein-coupled receptor kinase activity, because PMA
promoted desensitization of a mutated alpha2AAR that lacked G protein-coupled
receptor kinase phosphorylation sites was identical to that of wild-type
alpha2AAR. To test whether PKC phosphorylation is a mechanism by which alpha2AAR
can be regulated by other receptors, the alpha1bAR was co-expressed with the
alpha2AAR in Chinese hamster ovary cells. Upon selective activation of alpha1bAR,
the function of alpha2AAR underwent a 53 +/- 5% desensitization. Thus, cellular
events that result in PKC activation promote phosphorylation of the alpha2AAR and
lead to substantial desensitization of receptor function. This heterologous
regulation also represents a mechanism by which rapid crosstalk between the
alpha2AAR and other receptors can occur.
PMID- 9658189
TI - Protein-linked DNA strand breaks induced by NSC 314622, a novel noncamptothecin
topoisomerase I poison.
AB - NSC 314622 was found to have a cytotoxicity profile comparable to the
topoisomerase I (top1) inhibitors camptothecin (CPT) and saintopin in the
National Cancer Institute In Vitro Anticancer Drug Discovery Screen using the
COMPARE analysis. In vitro data showed that NSC 314622 induced DNA cleavage in
the presence of top1 at micromolar concentrations. Cleavage specificity was
different from CPT in that NSC 314622 did not cleave all sites induced by CPT
whereas some sites were unique to the NSC 314622 treatment. Top1-induced DNA
cleavage was also more stable than cleavage induced by CPT. NSC 314622 did not
induce DNA cleavage in the presence of human topoisomerase II. High
concentrations of NSC 314622 did not produce detectable DNA unwinding, which
suggests that NSC 314622 is not a DNA intercalator. DNA damage analyzed in human
breast carcinoma MCF7 cells by alkaline elution showed that NSC 314622 induced
protein-linked DNA single-strand breaks that reversed more slowly than CPT
induced strand breaks. CEM/C2, a CPT-resistant cell line because of a top1 point
mutation [Cancer Res 55:1339-1346 (1995)], was cross-resistant to NSC 314622.
These results demonstrate that NSC 314622 is a novel top1-targeted drug with a
unique chemical structure.
PMID- 9658190
TI - A crucial role for the mitogen-activated protein kinase pathway in nicotinic
cholinergic signaling to secretory protein transcription in pheochromocytoma
cells.
AB - The mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in
intracellular signaling, and this cascade may impinge on cAMP response elements
(CREs) of target genes. Both the MAPK pathway and chromogranin A expression may
be activated by cytosolic calcium influx, and calcium-dependent signals map onto
the chromogranin A promoter proximal CRE. We therefore probed the role of the
MAPK pathway in chromogranin A biosynthesis after secretory stimulation of PC12
pheochromocytoma cells by the nicotinic cholinergic pathway, the physiological
secretory trigger. Chemical inhibition of either MAPK or MAPK kinase blocked the
response of a transfected chromogranin A promoter to nicotine or protein kinase C
activation [by phorbol-12-myristate-13-acetate (PMA)], although nicotine-evoked
catecholamine secretion was unaffected. Activation of the MAP kinase cascade
(Ras, Raf, MAPK, or CREB kinase) by cotransfection of pathway components
stimulated the chromogranin A promoter. Cotransfection of MAPK pathway dominant
negative mutants (for Raf, MAPK, or CREB kinase) blocked nicotinic or PMA
activation of chromogranin A, although a dominant negative Ras mutant was without
effect. MAPK pathway enzymatic activity was stimulated by both nicotine and PMA.
Point mutations of the chromogranin A CRE suggested that this element was
necessary in cis for stimulation by nicotine, PMA, or chemical activation of the
MAPK pathway. Transfer of the CRE to a heterologous promoter conferred
inducibility by not only nicotine or cAMP but also MAPK activation. Expression of
the CREB antagonist KCREB blocked the response of the chromogranin A promoter to
nicotine, cAMP, or MAPK pathway activation by either chemical stimulation or
cotransfection of active cascade components. Chromogranin A mRNA responded to
MAPK pathway manipulation in a fashion similar to the transfected chromogranin A
promoter, in both direction and magnitude. We conclude that the MAPK pathway is a
necessary intermediate in signaling from the nicotinic receptor to secretory
protein transcription, although not to catecholamine secretion. In trans, this
response seems to involve the following signal cascade: protein kinase C --> Raf
-> MAPK kinase --> MAPK --> CREB kinase --> CREB. In cis, activation by the
cascade maps onto the chromogranin A promoter proximal CRE, which is both
necessary and sufficient to confer the response.
PMID- 9658191
TI - Sphingosine kinase mediates cyclic AMP suppression of apoptosis in rat periosteal
cells.
AB - Prostaglandin E stimulates bone formation in humans and animals, and increases
intracellular cAMP in osteoblastic cells. We found that cAMP inhibits apoptosis
in osteoblastic cells, and examined the mechanism of this effect. We report that
the cAMP elevating agent, forskolin, increases cell number in the rat periosteal
cell line (RP-11), by suppressing apoptosis in a cell type-specific manner. In RP
11, forskolin transiently up-regulates extracellular signal-regulated kinase
activity, a known suppressor of apoptosis. PD98059, a selective inhibitor of the
extracellular signal-regulated kinase pathway, only partially reverses the
antiapoptotic effect of forskolin, which suggests an additional mechanism for
cAMP action. We found that forskolin stimulates cytosolic sphingosine kinase
(SPK) activity in these cells; in two other osteoblastic cell lines, however,
forskolin does not suppress apoptosis. In contrast to the partial opposing effect
of PD98059 to forskolin action, N, N-dimethylsphingosine, a specific inhibitor of
SPK, completely reverses the antiapoptotic effect of forskolin, and has no effect
on apoptosis in the absence of forskolin. These findings show for the first time
that cAMP activates SPK in a cell-type-specific manner, and suggest that cAMP
suppression of apoptosis in RP-11 periosteal cells is mediated by its stimulation
of SPK.
PMID- 9658192
TI - Etoposide targets topoisomerase IIalpha and IIbeta in leukemic cells: isoform
specific cleavable complexes visualized and quantified in situ by a novel
immunofluorescence technique.
AB - We have shown that both DNA topoisomerase (topo) IIalpha and beta are in vivo
targets for etoposide using a new assay which directly measures topo IIalpha and
beta cleavable complexes in individual cells after treatment with topo II
targeting drugs. CCRF-CEM human leukemic cells were exposed to etoposide for 2
hr, then embedded in agarose on microscope slides before cell lysis. DNA from
each cell remained trapped in the agarose and covalently bound topo II molecules
from drug-stabilized cleavable complexes remained associated with the DNA. The
covalently bound topo II was detected in situ by immunofluorescence. Isoform
specific covalent complexes were detected with antisera specific for either the
alpha or beta isoform of topo II followed by a fluorescein isothiocyanate
conjugated second antibody. DNA was detected using the fluorescent stain Hoechst
33258. A cooled slow scan charged coupled device camera was used to capture
images. A dose-dependent increase in green immunofluorescence was observed when
using antisera to either the alpha or beta isoforms of topo II, indicating that
both isoforms are targets for etoposide. We have called this the TARDIS method,
for trapped in agarose DNA immunostaining. Two key advantages of the TARDIS
method are that it is isoform-specific and that it requires small numbers of
cells, making it suitable for analysis of samples from patients being treated
with topo II-targeting drugs. The isoform specificity will enable us to extend
our understanding of the mechanism of interaction between topo II-targeting
agents and their target, the two human isoforms.
PMID- 9658193
TI - Point mutation in intron sequence causes altered carboxyl-terminal structure in
the aryl hydrocarbon receptor of the most 2,3,7,8-tetrachlorodibenzo-p-dioxin
resistant rat strain.
AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent dioxin. There are
exceptionally wide inter- and intraspecies differences in sensitivity to TCDD
toxicity with Han/Wistar (H/W) (Kuopio) rats being the most resistant mammals
tested. A peculiar feature of H/W rats is that despite their unresponsiveness to
the acute lethality of TCDD, their sensitivity to other biological impacts of
TCDD (e.g., CYP1A1 induction) is preserved. The biological effects of TCDD are
mediated by the aryl hydrocarbon receptor (AhR). We recently found that the AhR
of H/W rats (about 98 kDa) is smaller than the receptor in other rat strains (106
kDa). In the present study, molecular cloning and sequencing of the H/W rat AhR
revealed that the reason for its smaller size is a deletion/insertion-type change
at the 3' end of exon 10 in the receptor cDNA. This change emanates from a single
point mutation at the first nucleotide of intron 10, resulting in altered mRNA
splicing. At the protein level, the mutation leads to a total loss of either 43
or 38 amino acids (with altered sequence for the last seven amino acids in the
latter case) toward the carboxyl-terminal end in the trans-activation domain of
the AhR. H/W rats also harbor a point mutation in exon 10 that will cause a Val
to-Ala substitution in codon 497, but this occurs in a variable region of the
AhR. These findings suggest that there is a relatively small region in the AhR
trans-activation domain that may be capable of providing selectivity to its
function.
PMID- 9658194
TI - Effector pathway-dependent relative efficacy at serotonin type 2A and 2C
receptors: evidence for agonist-directed trafficking of receptor stimulus.
AB - There are many examples of a single receptor coupling directly to more than one
cellular signal transduction pathway. Although traditional receptor theory allows
for activation of multiple cellular effectors by agonists, it predicts that the
relative degree of activation of each effector pathway by an agonist (relative
efficacy) must be the same. In the current experiments, we demonstrate that
agonists at the human serotonin2A (5-HT2A) and 5-HT2C receptors activate
differentially two signal transduction pathways independently coupled to the
receptors [phospholipase C (PLC)-mediated inositol phosphate (IP) accumulation
and phospholipase A2 (PLA2)-mediated arachidonic acid (AA) release]. The relative
efficacies of agonists differed depending on which signal transduction pathway
was measured. Moreover, relative to 5-HT, some 5-HT2C agonists (e.g., 3
trifluoromethylphenyl-piperazine) preferentially activated the PLC-IP pathway,
whereas others (e.g., lysergic acid diethylamide) favored the PLA2-AA pathway. In
contrast, when two dependent responses were measured (IP accumulation and calcium
mobilization), agonist relative efficacies were not different. These data
strongly support the hypothesis termed "agonist-directed trafficking of receptor
stimulus" recently proposed by Kenakin [Trends Pharmacol Sci 16:232-238 (1995)].
Concentration-response curves to 5-HT2C agonists were fit well by a three-state
model of receptor activation, suggesting that two active receptor states may be
sufficient to explain pathway-dependent agonist efficacy. Rational drug design
that optimizes preferential effector activity within a group of receptor
selective drugs holds the promise of increased selectivity in clinically useful
agents.
PMID- 9658195
TI - Differential response of estrogen receptor alpha and estrogen receptor beta to
partial estrogen agonists/antagonists.
AB - The existence of two rather than one estrogen receptor, today characterized as
estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), indicates
that the mechanism of action of 17beta-estradiol and related synthetic drugs is
more complex than previously thought. Because the homology of amino acid residues
in the ligand-binding domain (LBD) of ERbeta is high compared with those amino
acid residues in ERalpha LBD, previously shown to line the ligand binding cavity
or to make direct contacts with ligands, it is not surprising that many ligands
have a similar affinity for both receptor subtypes. We report that 17alpha
ethynyl, 17beta-estradiol, for example, has an ERalpha-selective agonist potency
and that 16beta,17alpha-epiestriol has an ERbeta-selective agonist potency. We
also report that genistein has an ERbeta-selective affinity and potency but an
ERalpha-selective efficacy. Furthermore, we show that tamoxifen, 4-OH-tamoxifen,
raloxifene, and ICI 164,384 have an ERalpha-selective partial agonist/antagonist
function but a pure antagonist effect through ERbeta. In addition, raloxifene
displayed an ERalpha-selective antagonist potency, in agreement with its ERalpha
selective affinity. However, although ICI 164,384 showed an ERbeta-selective
affinity, it had a similar potency to antagonize the effect of 17beta-estradiol
in the ERalpha- and ERbeta-specific reporter cell lines, respectively. In
conclusion, our data indicate that the ligand binding cavity of ERbeta is
probably more different from that of ERalpha than can be anticipated from the
primary sequences of the two ER subtypes and that it will be possible to develop
receptor-specific ligands that may form the basis of novel pharmaceuticals with
better in vivo efficacy and side effect profile than current available drugs.
PMID- 9658196
TI - Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by
the H1 receptor blocker cetirizine compared with other second-generation
antihistamines.
AB - In the current study, the potential blocking ability of K+ channels encoded by
the human ether-a-go-go related gene (HERG) by the piperazine H1 receptor
antagonist cetirizine has been examined and compared with that of other second
generation antihistamines (astemizole, terfenadine, and loratadine). Cetirizine
was completely devoid of any inhibitory action on HERG K+ channels heterologously
expressed in Xenopus laevis oocytes in concentrations up to 30 microM. On the
other hand, terfenadine and astemizole effectively blocked HERG K+ channels with
nanomolar affinities (the estimated IC50 values were 330 and 480 nM,
respectively), whereas loratadine was approximately 300-fold less potent (IC50
approximately 100 microM). In addition, in contrast to terfenadine, cetirizine
did not show use-dependent blockade. In SH-SY5Y cells, a human neuroblastoma
clone that constitutively expresses K+ currents carried by HERG channels (IHERG),
as well as in human embryonic kidney 293 cells stably transfected with HERG cDNA,
extracellular perfusion with 3 microM cetirizine did not exert any inhibitory
action on IHERG. Astemizole (3 microM), on the other hand, was highly effective.
Terfenadine (3 microM) caused a marked (approximately 80%) inhibition of IHERG in
SH-SY5Y cells, whereas loratadine, at the same concentration, caused a 40%
blockade. Furthermore, the application of cetirizine (3 microM) on the
intracellular side of the membrane of HERG-transfected human embryonic kidney 293
cells did not affect IHERG, whereas the same intracellular concentration of
astemizole caused a complete block. The results of the current study suggest that
second-generation antihistamines display marked differences in their ability to
block HERG K+ channels. Cetirizine in particular, which possesses more polar and
smaller substituent groups attached to the tertiary amine compared with other
antihistamines, lacks HERG-blocking properties, possibly explaining the absence
of torsade de pointes ventricular arrhythmias associated with its therapeutical
use.
PMID- 9658197
TI - Regulation of adenylyl cyclase type V/VI in smooth muscle: interplay of
inhibitory G protein and Ca2+ influx.
AB - The characteristics of inhibitory regulation of adenylyl cyclase V/VI by Ca2+ and
G proteins were examined in dispersed gastric smooth muscle cells. The mechanisms
were evoked separately, sequentially, or concurrently using ligand-gated and G
protein-coupled receptor agonists and receptor-independent probes (e. g,
thapsigargin). During the initial phase of agonist stimulation, alpha,beta
methylene-ATP, UTP, and ATP inhibited forskolin-stimulated cAMP formation in a
concentration-dependent fashion. Inhibition by alpha,beta-methylene-ATP, which
activates ligand-gated P2X receptors, was abolished by zero Ca2+, whereas
inhibition by UTP, which activates P2Y2 receptors coupled to Gq/11 and Gi3, was
not affected by zero Ca2+ but was abolished by pertussis toxin (PTX). Inhibition
by ATP, which activates both P2X and P2Y2 receptors, was not affected by zero
Ca2+ alone; but after inhibition mediated by Galphai3 was blocked with PTX,
inhibition by Ca2+ influx was unmasked and was abolished by zero Ca2+. Inhibition
by cholecystokinin-8 was observed only during the phase of capacitative Ca2+
influx and was blocked by zero Ca2+. Inhibition by UTP during this phase was not
affected by zero Ca2+ alone; but after inhibition mediated by Galphai3 was
blocked with PTX, inhibition by Ca2+ influx was unmasked and was abolished by
zero Ca2+. Inhibition of adenylyl cyclase V/VI activity in smooth muscle can be
mediated independently by inhibitory G proteins and Ca2+ influx but is
exclusively mediated by inhibitory G proteins when both mechanisms are triggered.
PMID- 9658198
TI - Ligand specificity of the genetic variants of human alpha1-acid glycoprotein:
generation of a three-dimensional quantitative structure-activity relationship
model for drug binding to the A variant.
AB - Human alpha1-acid glycoprotein (AAG) is a mixture of at least two genetic
variants: the A variant and the F1 and/or S variant or variants, which are
encoded by two different genes. In a continuation of previous studies indicating
specific drug transport roles for each AAG variant according to its separate
genetic origin, this work was designed to (1) determine the affinities of the two
main gene products of AAG (i.e., the A variant and a mixture of the F1 and S
variants) for 35 chemically diverse drugs and (2) to obtain meaningful 3D-QSARs
for each binding site. Affinities were obtained by displacement experiments,
leading to qualitative indications about binding site characteristics. In
particular, drugs binding selectively to the A variant displayed some common
structural features, but this was not seen for the F1*S variants. Three
dimensional QSAR analyses using the CoMFA method yielded a steric model for
binding to the A variant, from which a simplified haptophoric model was derived.
In contrast, no statistically sound model was found for the F1*S variants,
possibly due (among other reasons) to an insufficient number of high affinity
ligands in the set.
PMID- 9658199
TI - Identification of a [3H]Ligand for the common allosteric site of muscarinic
acetylcholine M2 receptors.
AB - Muscarinic acetylcholine receptors bind allosteric modulators at a site apart
from the orthosteric site used by conventional ligands. We tested in cardiac
tissue whether modulator binding to ligand-occupied muscarinic M2 receptors is a
preferential event that can be detected using a radioactive allosteric agent. The
newly synthesized dimethyl-W84 (N,N'-bis[3-(1,3-dihydro-1, 3-dioxo-4-methyl-2H
isoindol-2-yl)propyl]-N,N,N',N'-tetramethyl-1, 6-hexanediaminium diiodide) has a
particular high potency at M2 receptors occupied by the conventional antagonist N
methylscopolamine (NMS); dissociation of [3H]NMS is half-maximally retarded at an
EC50,diss value of 3 nM. Using obidoxime as an "allosteric antagonist," evidence
was found that dimethyl-W84 interacts with the postulated common allosteric site.
Binding of [3H]dimethyl-W84 (0.3 nM; specific activity, 168 Ci/mmol) was measured
in porcine heart homogenates (4 mM Na2HPO4, 1 mM KH2PO4, pH 7.4, 23 degrees) in
the presence of 1 microM NMS. Homologous competition experiments revealed two
components of saturable radioligand binding: one with a high affinity (KD = 2 nM)
and small capacity ( approximately 30% of total saturable binding) and the other
with a 20,000-fold lower affinity. The Bmax value of the high affinity sites (68
fmol/mg protein) matched muscarinic receptor density as determined by [3H]NMS (79
fmol/mg). Prototype allosteric agents, alcuronium, W84 (the parent compound of
the radioligand), and gallamine, displaced high affinity [3H]dimethyl-W84 binding
concentration-dependently (pKi values = 8.62, 7.83, and 6.72, respectively). The
binding affinities of the modulators were in excellent correlation with their
potencies to allosterically stabilize NMS/receptor complexes (EC50,diss = 8.40,
7.72, and 6.74, respectively). We conclude that high affinity binding of
[3H]dimethyl-W84 reflects occupation of the common allosteric site of M2
receptors.
PMID- 9658200
TI - Mutations at lipid-exposed residues of the acetylcholine receptor affect its
gating kinetics.
AB - The firmest candidate among the transmembrane portions of the nicotinic
acetylcholine receptor (AChR) to be in contact with the lipid bilayer is the
fourth segment, M4. To explore the contribution of alphaM4 amino acid residues of
mouse AChR to channel gating, we combined site-directed mutagenesis with single
channel recordings. Two residues in alphaM4, Cys418 and Thr422, were found to
significantly affect gating kinetics when replaced by alanine. AChRs containing
alphaC418A and alphaT422A subunits form channels characterized by a 3- and 5-fold
reduction in the mean open time, respectively, suggesting an increase in the
closing rate due to the mutations. The calculated changes in the energy barrier
for the channel closing process show unequal and coupled contributions of both
positions to channel gating. Single-channel recordings of hybrid wild-type
alpha/alphaT422A AChR show that the closing rate depends on the number of alpha
subunits mutated. Each substitution of threonine to alanine changes the energy
barrier of the closing process by approximately 0.5 kcal/mol. Recordings of
channels activated by high agonist concentration suggest that these mutations
also impair channel opening. Both Cys418 and Thr422 have been postulated to be in
contact with the lipid milieu and are highly conserved among species and
subunits. Our results support the involvement of lipid-exposed residues in
alphaM4 in AChR channel gating mechanism.
PMID- 9658201
TI - Chimeric melanocortin MC1 and MC3 receptors: identification of domains
participating in binding of melanocyte-stimulating hormone peptides.
AB - The melanocortin receptors MC1 and MC3 are G protein-coupled receptors that have
substantial structural similarities and bind melanocyte peptides but with
different affinity profiles. We constructed a series of chimeric MC1/MC3
receptors to identify the epitopes that determine their selectivities for natural
melanocyte peptides and synthetic analogues. The chimeric constructs were made by
a polymerase chain reaction that used identical regions in or just outside
transmembranes (TM) 1, 4, and 6 and divided the receptors into four segments.
Saturation and competition studies on the expressed chimeric proteins indicate
that TM1, TM2, TM3, and TM7 are involved in the subtype-specific binding of
melanocyte peptides to these receptors. The results support the hypothesis that
TM4 and TM5 may not contribute to the ligand-binding specificity of the MC
receptors. This is the first report to describe the subtype-specific hormone
binding domains of the melanocortin receptor family.
PMID- 9658202
TI - Structural determinants of potency and stereoselective block of hKv1.5 channels
induced by local anesthetics.
AB - Block of hKv1.5 channels by bupivacaine is stereoselective, with (R)-(+)
bupivacaine being 7-fold more potent than (S)-(-)-bupivacaine. The study of the
effects of chemically related enantiomers on these channels may help to elucidate
the structural determinants of stereoselective hKv1.5 channels block by local
anesthetics. In this study, we analyzed the effects of (R)-(+)-ropivacaine, (R)
(+)-mepivacaine, and (S)-(-)-mepivacaine on hKv1.5 channels stably expressed in
Ltk- cells. (R)-(+)-Ropivacaine inhibited hKv1.5 current and induced a fast
initial decline superimposed to the slow inactivation during the application of
depolarizing pulses, which reached steady state at the end of 250-msec
depolarizing pulses. The concentration-dependence block induced by (R)-(+)
ropivacaine yielded a KD value of 32 +/- 1 microM [i.e., 2.5-fold more potent
than (S)-(-)-ropivacaine]. (R)-(+)-Ropivacaine block also was voltage dependent,
with a fractional electrical distance (delta) of 0.156 +/- 0.003 (n = 14)
referred to the inner surface. Both (S)-(-)- and (R)-(+)-mepivacaine blocked
hKv1.5 channels, with KD values of 286.8 +/- 34.1 and 379.0 +/- 56.0 microM,
respectively [i.e., block was not stereoselective (p > 0.05)]. (S)-(-)
Mepivacaine and (R)-(+)-mepivacaine block displayed no apparent time-dependence
due to a very fast dissociation rate constant. However, block by mepivacaine
enantiomers was voltage dependent, with delta values of 0.154 +/- 0.015 and 0.160
+/- 0.008 for the (S)-(-)- and (R)-(+)-enantiomers, respectively. We conclude
that (1) (R)-(+)-ropivacaine and mepivacaine enantiomers block the open state of
hKv1.5 channels and (2) the length of their alkyl substituent at position 1
determines the potency and the degree of stereoselectivity.
PMID- 9658203
TI - Access to hematin: the basis of chloroquine resistance.
AB - The saturable uptake of chloroquine by parasites of Plasmodium falciparum has
been attributed to specific carrier-mediated transport of chloroquine. It is
suggested that chloroquine is transported in exchange for protons by the parasite
membrane Na+/H+ exchanger [J Biol Chem 272:2652-2658 (1997)]. Once inside the
parasite, it is proposed that chloroquine inhibits the polymerization of hematin,
allowing this toxic hemoglobin metabolite to accumulate and kill the cell
[Pharmacol Ther 57:203-235 (1993)]. To date, the contribution of these proposed
mechanisms to the uptake and antimalarial activity of chloroquine has not been
assessed. Using sodium-free medium, we demonstrate that chloroquine is not
directly exchanged for protons by the plasmodial Na+/H+ exchanger. Furthermore,
we show that saturable chloroquine uptake at equilibrium is due solely to the
binding of chloroquine to hematin rather than active uptake: using Ro 40-4388, a
potent and specific inhibitor of hemoglobin digestion and, by implication,
hematin release, we demonstrate a concentration-dependent reduction in the number
of chloroquine binding sites. An equal number of chloroquine binding sites are
found in both resistant and susceptible clones, but the apparent affinity of
chloroquine binding is found to correlate with drug activity (r2 = 0.93, p <
0.0001). This completely accounts for both the reduced drug accumulation and
activity observed in resistant clones and the "reversal" of resistance produced
by verapamil. The data presented here reconcile most of the available biochemical
data from studies of the mode of action of chloroquine and the mechanism of
chloroquine resistance. We show that the activity of chloroquine and amodiaquine
is directly dependent on the saturable binding of the drugs to hematin and that
the inhibition of hematin polymerization may be secondary to this binding. The
chloroquine-resistance mechanism regulates the access of chloroquine to hematin.
Our model is consistent with a resistance mechanism that acts specifically at the
food vacuole to alter the binding of chloroquine to hematin rather than changing
the active transport of chloroquine across the parasite plasma membrane.
PMID- 9658204
TI - Human platelets and polymorphonuclear leukocytes synthesize oxygenated
derivatives of arachidonylethanolamide (anandamide): their affinities for
cannabinoid receptors and pathways of inactivation.
AB - Arachidonylethanolamide (AEA), the putative endogenous ligand of the cannabinoid
receptor, has been shown to be a substrate for lipoxygenase enzymes in vitro. One
goal of this study was to determine whether lipoxygenase-rich cells metabolize
AEA. [14C]AEA was converted by human polymorphonuclear leukocytes (PMNs) to two
major metabolites that comigrated with synthetic 12(S)- and 15(S)-hydroxy
arachidonylethanolamide (HAEA). Human platelets convert [14C]AEA to 12(S)-HAEA.
12(S)-HAEA binds to both CB1 and CB2 receptors with approximately the same
affinity as AEA. 12(R)-HAEA, which is not produced by PMNs, has 2-fold lower
affinity for the CB1 receptor and 10-fold lower affinity for the CB2 receptor
than 12(S)-HAEA. 15-HAEA has a lower affinity than AEA for both receptors, with
Ki values of 738 and >1000 nM for CB1 and CB2 receptors, respectively. The
addition of a hydroxyl group at C20 of AEA resulted in a ligand with the same
affinity for the CB1 receptor but a 4-fold lower affinity for the CB2 receptor
than AEA. 12(S)-HAEA and 15-HAEA are poor substrates for AEA amidohydrolase and
do not bind to the AEA uptake carrier. In conclusion, the addition of a hydroxyl
group at C12 of the arachidonate backbone of AEA does not affect binding to CB
receptors but is likely to increase its half-life. The addition of hydroxyl
groups at other positions affects ligand affinity for CB receptors; both the
position of the hydroxyl group and the configuration of the remaining double
bonds are determinants of affinity.
PMID- 9658205
TI - Molecular basis for differential inhibition of glutamate transporter subtypes by
zinc ions.
AB - Zinc ions (Zn2+) are stored in synaptic vesicles with glutamate in a number of
regions of the brain. When released into the synapse, Zn2+ modulates the activity
of various receptors and ion channels. Excitatory amino acid transporters (EAATs)
maintain extracellular glutamate concentrations below toxic levels and regulate
the kinetics of glutamate receptor activation. We have investigated the actions
of Zn2+ on two of the most abundant human excitatory amino acid transporters,
EAAT1 and EAAT2. Zn2+ is a noncompetitive, partial inhibitor of glutamate
transport by EAAT1 with an IC50 value of 9.9 +/- 2.3 microM and has no effect on
glutamate transport by EAAT2 at concentrations up to 300 microM. Glutamate and
aspartate transport by EAAT1 are associated with an uncoupled chloride
conductance, but Zn2+ selectively inhibits transport and increases the relative
chloride flux through the transporter. We have investigated the molecular basis
for differential inhibition of EAAT1 and EAAT2 by Zn2+ using site-directed
mutagenesis and demonstrate that histidine residues of EAAT1 at positions 146 and
156 form part of the Zn2+ binding site. EAAT2 contains a histidine residue at the
position corresponding to histidine 146 of EAAT1, but at the position
corresponding to histidine 156 of EAAT1, EAAT2 has a glycine residue. Mutation of
this glycine residue in EAAT2 to histidine generates a Zn2+ sensitive
transporter, further confirming the role of this residue in conferring
differential Zn2+ sensitivity.
PMID- 9658206
TI - The biophysical and pharmacological characteristics of skeletal muscle ATP
sensitive K+ channels are modified in K+-depleted rat, an animal model of
hypokalemic periodic paralysis.
AB - We evaluated the involvement of the sarcolemmal ATP-sensitive K+ channel in the
depolarization of skeletal muscle fibers occurring in an animal model of human
hypokalemic periodic paralysis, the K+-depleted rat. After 23-36 days of
treatment with a K+-free diet, an hypokalemia was observed in the rats. No
difference in the fasting insulinemia and glycemia was found between normokalemic
and hypokalemic rats. The fibers of the hypokalemic rats were depolarized. In
these fibers, the current of sarcolemmal ATP-sensitive K+ channels measured by
the patch-clamp technique was abnormally reduced. Cromakalim, a K+ channel
opener, enhanced the current and repolarized the fibers. At channel level, two
open conductance states blocked by ATP and stimulated by cromakalim were found in
the hypokalemic rats. The two states could be distinguished on the basis of their
slope conductance and open probability and were never detected on muscle fibers
of normokalemic rats. It is known that insulin in humans affected by hypokalemic
periodic paralysis leads to fiber depolarization and provokes paralysis. We
therefore examined the effects of insulin at macroscopic and single-channel level
on hypokalemic rats. In normokalemic animals, insulin applied in vitro to the
muscles induced a glybenclamide-sensitive hyperpolarization of the fibers and
also stimulated the sarcolemmal ATP-sensitive K+ channels. In contrast, in
hypokalemic rats, insulin caused a pronounced fiber depolarization and reduced
the residual currents. Our data indicated that in hypokalemic rats, an abnormally
low activity of ATP-sensitive K+ channel is responsible for the fiber
depolarization that is aggravated by insulin.
PMID- 9658207
TI - Activation of soluble guanylyl cyclase by the nitrovasodilator 3
morpholinosydnonimine involves formation of S-nitrosoglutathione.
AB - Soluble guanylyl cyclase (sGC) is the major physiological target of sydnonimine
based vasodilators such as molsidomine. Decomposition of sydnonimines results in
the stoichiometric formation of nitric oxide (NO) and superoxide (O2-), which
rapidly react to form peroxynitrite. Inasmuch as sGC is activated by NO but not
by peroxynitrite, we investigated the mechanisms underlying sGC activation by 3
morpholinosydnonimine (SIN-1). Stimulation of purified bovine lung sGC by SIN-1
was found to be strongly dependent on glutathione (GSH). By contrast, GSH did not
affect sGC activation by NO released from 2,2-diethyl-1-nitroso-oxyhydrazine,
indicating that NO/O2- released from SIN-1 converted GSH to an activator of sGC.
High performance liquid chromatography identified this product as the thionitrite
S-nitrosoglutathione. Further, the reaction product decomposed to release NO upon
addition of Cu(NO3)2 in the presence of GSH. Activation of sGC was antagonized by
the Cu(I)-specific chelator neocuproine, whereas the Cu(II)-selective drug
cuprizone was less potent. Carbon dioxide (delivered as NaHCO3) antagonized S
nitrosation by peroxynitrite but not by SIN-1. Thus, NO/O2- released from SIN-1
mediates a CO2-insensitive conversion of GSH to S-nitrosoglutathione, a
thionitrite that activates sGC via trace metal-catalyzed release of NO. These
results may provide novel insights into the molecular mechanism underlying the
nitrovasodilator action of SIN-1.
PMID- 9658208
TI - Sensitivity to cisplatin and platinum-containing compounds of Schizosaccharomyces
pombe rad mutants.
AB - The role of genes that affect response to radiation in determining sensitivity to
platinum-containing compounds was studied using a panel of 23 strains of the
yeast Schizosaccharomyces pombe. The radiation-hypersensitive mutants all had the
same genetic background and most of them contained mutations that disabled either
cell cycle checkpoints or DNA repair. The tested platinum compounds included
cisplatin and two complexes containing diaminocyclohexane (oxaliplatin and
tetraplatin), two ammine/cyclohexylamine complexes with different orientation of
the leaving groups (JM216 and JM335) and a multinuclear platinum complex (BBR
3464). The cytotoxic effect of the selected platinum complexes was evaluated by
using a microtiter growth inhibition assay with a 48 hr exposure to drug. The
mutants fell into three groups with respect to sensitivity to cisplatin: four
mutants (rad2, -7, -11, -15) exhibited minimal change in sensitivity; fifteen
mutants (rad4-6, -8-10, -12-14, -16-17, -19-21, and -22) were 5.1-21.7-fold
hypersensitive; only rad1 and -3 mutants, defective in checkpoints, and rad18,
defective in repair, displayed a marked hypersensitivity. None of the mutants
demonstrated appreciable change in sensitivity to JM216 presumably as a
consequence of a lack of resistance of the wild-type strain, whereas a moderate
increase in sensitivity to JM335 was observed for most of the mutants, and
hypersensitivity to BBR3464 was observed only in rad1 and -3. No relevant changes
in sensitivity to tetraplatin were observed. Most of the mutants, with the
exception of rad2, -7, and -15, were hypersensitive to oxaliplatin. These
findings demonstrate that specific mutations have disparate effects on the
profile of sensitivity to different members of the same class of cytotoxic
agents, which provides genetic evidence that different mechanisms are involved in
differential cytotoxicity induced by Pt compounds. The results also demonstrate
the utility of such a panel of mutants, constructed on the same genetic
background, for detecting specific cellular response; presumably, this reflects
the recognition or processing of specific DNA adducts. In conclusion, because the
rad1 and rad3 gene products are determinants of cellular response to a large
number of platinum-containing compounds, the present results support a critical
role of genes involved in cell cycle control in cellular sensitivity to these
agents.
PMID- 9658210
TI - Confidentiality in the editorial process
PMID- 9658209
TI - A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents.
AB - The slowly activating delayed rectifier K+ current, IKs, is an important
modulator of cardiac action potential repolarization. Here, we describe a novel
benzodiazepine, [L-364,373 [(3-R)-1, 3-dihydro-5-(2-fluorophenyl)-3-(1H-indol-3
ylmethyl)-1-methyl-2H- 1,4-benzodiazepin-2-one] (R-L3), that activates IKs and
shortens action potentials in guinea pig cardiac myocytes. These effects were
additive to isoproterenol, indicating that channel activation by R-L3 was
independent of beta-adrenergic receptor stimulation. The increase of IKs by R-L3
was stereospecific; the S-enantiomer, S-L3, blocked IKs at all concentrations
examined. The increase in IKs by R-L3 was greatest at voltages near the threshold
for normal channel activation, caused by a shift in the voltage dependence of IKs
activation. R-L3 slowed the rate of IKs deactivation and shifted the half-point
of the isochronal (7.5 sec) activation curve for IKs by -16 mV at 0.1 microM and
24 mV at 1 microM. R-L3 had similar effects on cloned KvLQT1 channels expressed
in Xenopus laevis oocytes but did not affect channels formed by coassembly of
KvLQT1 and hminK subunits. These findings indicate that the association of minK
with KvLQT1 interferes with the binding of R-L3 or prevents its action once bound
to KvLQT1 subunits.
PMID- 9658211
TI - Drug surveillance: topics for discussion and prospects
AB - Drug surveillance can be grouped into two areas. The first includes registration
and inspection, activities that are more familiar to society at large. The second
involves research and monitoring of adverse effects. Brazilian legislation has
regulated this subject since 1970. A recent directive also provides for a
national pharmaceutical surveillance system. This current article provides an
overview of the history, definitions, pharmacological concepts, classification,
and diagnosis of the adverse effects of drugs. An analysis is presented of the
goals and sources of information for drug monitoring as well as some Brazilian
experience in this field.
PMID- 9658212
TI - Domestic water use in a rural village in minas gerais, brazil, with an enphasis
on spatial patterns, sharing of water, and factors in water use
AB - This paper examines the relationship between domestic water use and
socioeconomic, environmental, and spatial parameters at the household level in a
small rural village in northern Minas Gerais State. Five methods are used -
direct observation, household interviews, self-reporting by households,
regression analysis, and statistical mapping. Results show that water use is
characterized by 1) generally low but widely fluctuating values per person per
day, 2) sharing of water sources between households, 3) the use of multiple
sources by individual households, 4) avoidance of heavily contaminated stream
sites, and 5) predominance of socioeconomic factors in water use. Households
owning their own water supply used, on average, 25.3 liters per person/day and
those without a supply 9. 0 l, with higher use of the local streams among the
latter. Water use varied spatially. The socioeconomic factors house quality,
latrine ownership, type of watersource, and a utility index were significantly
correlated with water use. Implications of this simple household water sources
and the more deficient sanitary facilities for potential water-borne disease
transmission are briefly discussed and suggestions made for further improvements.
This study confirms the appropriateness of the application of direct observation,
interview, and microgeographical methods for quantitative water use studies.
PMID- 9658214
TI - Emergency care costs for victims of violence treated at two hospitals in rio de
janeiro
AB - The following is a cost analysis of one month of emergency room treatment
provided for different types of injuries at two public hospitals in Rio de
Janeiro. The study focused on the following: 1) costs at each hospital for
treatment of different injuries (annual and monthly estimates); 2) mean cost of
each injury; 3) detailed itemized costs of care (materials and drugs, surgery,
standard procedures, tests, professional fees, and meals). The items were
investigated at the respective hospitals and included services, materials, and
resources employed in treating the 1,053 patients included in the sample (498 in
the Miguel Couto Municipal Hospital - MCMH - and 555 in the Salgado Filho
Municipal Hospital - SFMH). Traffic accidents (run-over pedestrians, motor
vehicle collisions, and transportation accidents) accounted for 74.3% of costs at
MCMH and 48.4% at SFMH. Injuries due to aggression were also considered relevant
in the cost profile, mainly at SFMH (49% of costs due to violence) as compared to
24.9% of the total care costs at MCMH. Mean treatment costs for pedestrians run
over by motor vehicles varied from R$77.76 (SFMH) to R$237.77 (MCMH). Mean
treatment costs for victims of aggression varied from R$107.35 (SFMH) to R$84.19
(MCMH). The study suggests public health measures to deal with and prevent
violence.
PMID- 9658215
TI - From complaints to impunity: a morbidity and mortality profile of children
suffering violence
AB - This article analyzes complaints of violence against children and the procedures
subsequent to their filing. The methodology, largely qualitative, was two
pronged, involving an analysis of data from the year 1990 from the police
precincts in Program Areas 1 and 5 in the city of Rio de Janeiro and a discussion
on the follow-up of complaints five years after the events. The conclusion was
that motor vehicle accidents are the most common cause of violence against
children. Almost no information had been recorded about the circumstances in
which the violent events occurred. Further, nothing had been done to elucidate
the perpetrators' liability.
PMID- 9658216
TI - Premature birth and its repercussions on growth and development in guadalajara,
jalisco, Mexico
AB - This study focuses on the repercussions of prematurity for the growth and
development of newborns from hospitals in Guadalajara, Jalisco, Mexico, typical
of the health care system in Mexico. Infants were assessed every six months as to
nutritional status and the Denver Selective Test. In analyzing the results,
social groups were considered determinant categories for studying prematurity as
the dependent variable. The results shows that both prematurity and social group
are risk factors to be considered by the public health field when designing
health care programs.
PMID- 9658217
TI - Prevalence of vibrio cholerae O(1) infection in manacapuru, amazonas state,
brazil (1992)
AB - This study focused on the prevalence of V. cholerae O(1) infection in 1,196
individuals living in Manacapuru, Amazonas State, through microtitering of
vibriocidal antibody and somatic agglutination test. The role of living
conditions and individual characteristics as possible risk factors for infection
was also assessed. Vibriocidal titers >/= 1: 40 and/or agglutinating titers >/=
1: 80 were considered indicators of V. cholerae O(1) infection. Infection
prevalence was 25.7%. There was no significant statistical difference (p=0.05)
when analyzed against housing patterns, sanitary facilities, source and treatment
of water, destination of domestic waste, sex, or profession. Household location,
number of occupants/household, age, and schooling showed significant statistical
differences in infection prevalence (p=0.05).
PMID- 9658218
TI - The relationship between family violence and teenage aggressiveness
AB - The following is an exploratory study on family violence in two different
schools, public and the other private, Porto Alegre, Rio Grande do Sul. Seventy
six families were interviewed, 36 with adolescents classified as aggressive by
teachers and 40 with non-aggressive adolescents. Total number of subjects was
213. Physical and severe violence, frequent or occasional, was present in more
than half of the sample: 41 reports - 53.9%. A third of the cases occurred in the
private school (37%), with twice as many in the public school (63%). However,
rates of severe or frequent episodes were similar in both schools. The
relationship between violent behavior by teenagers and physical punishment by
parents was significant. That is, aggressive adolescents were punished more than
non-aggressive ones (odds ratio = 4.3). Prevalence of physical abuse was higher
in the older, male teenager group, in the presence of sibling aggression, and in
low-income and dysfunctional families. The study shows that physical abuse is
more present in society than we would like to imagine.
PMID- 9658219
TI - A statistical model for defining priority geographic areas for the control of
neonatal tetanus
AB - We applied factor analysis to indicators of health and living conditions from
Brazilian states in order to define geographic areas at potential risk for
neonatal tetanus. Two factors, namely 'health profile in the rural area' and
'proportional mortality on neonatal tetanus' were selected and plotted against
each other. A cluster composed of States from the Northeast plus Para and Amapa
was found to include most neonatal tetanus risk areas and a low case-reporting
rate. Another cluster included States from the Southeast and South and displayed
a neonatal tetanus reporting rate that was compatible with that for other
indicators. Espirito Santo, however, was found to be a silent productive area.
The Federal District appeared alone, showing the best health conditions. Finally,
the States of the Middle West and Roraima constituted the last cluster,
characterized by intermediate health status and high neonatal tetanus case
reporting rate. Our results were consistent with the overall Brazilian health
profile, distinguishing the North and Northeast from the South and Southeast,
with the Middle West in an intermediate position.
PMID- 9658220
TI - Restructuring of production and workers' health: a case study
AB - We performed a case study on a company focusing on the form of management and the
shop floor workers, in order to identify the possible effects of participant work
strategies on workers' health. Data on the company included its history, type of
management, and organization of both production and the work process. Data on
shop floor workers included age, schooling, perceptions of work, family life,
recreation, and self-reported disease history. We concluded that the
characteristics of the management model adopted by the company originated from
ideas imported from Japan, including flexibilization of production, outsourcing,
performance of multiple tasks, and participation in the work process. Workers
referred to participation in the work process in an ambiguous tone. Some reported
positive effects, like greater freedom and respect, with positive effects on life
both inside and outside the workplace. For part of the group studied, the
characteristics of the work organization model practiced in the company had
negative effects on health, leading them to complain of insomnia, nervousness,
work-related dreams, and headaches.
PMID- 9658221
TI - Citizenship, people's participation, and health: beneficiaries of the public
health services network have their say
AB - This paper deals with issues of citizenship and people's participation in health
services, based on an analysis of concepts displayed by a specific group, i.e.,
users of Primary Care Clinics in Program Area 3.1 in the city of Rio de Janeiro,
Brazil. The paper analyzes health care users' ideas as the ones most heavily
influencing the chapter on health in the Brazilian Constitution. The historical
context is the discussion underway on the role of patients in the relationship to
professional health care providers, who in turn face the challenge of building a
'health and hygiene mentality' among the people. Data were gathered through a
field study using a qualitative social research methodology and identify salient
points among the ideas of people receiving care. There was a gap (or distortion)
in their concept of citizenship alongside aspects which, if analyzed according to
the subjective plane of these social agents, show that they expect channels to be
created by which they can express their opinions, particularly at the practical
level. The analysis thus points to the strategic role of day-to-day relationships
in the social change process and the acquisition of rights, meanwhile seeking to
shed light on the feasibility of this process in view of the subjectivity of the
agents giving it life.
PMID- 9658222
TI - Birth profile for the city of rio de janeiro: a spatial analysis
AB - This article analyzes the birth profile by neighborhood in the city of Rio de
Janeiro, using data for 1994 from the Data Base on Live Births. Pattern maps were
employed in addition to the Moran I statistical test to detect spatial
clustering. Proportions of live newborns with an Apgar score of 8-10, cesareans,
mothers with greater than a secondary school education, and teenage mothers
displayed visually identifiable spatial patterns and significant spatial self
correlation. Low birth weight displayed a random pattern, indicating that on this
scale of analysis, this indicator does not distinguish risk groups, despite its
unquestionable predictive value for child morbidity/mortality at the individual
level. The Apgar score, despite the high number of non-responses in some
neighborhoods, showed a pattern more consistent with the distribution of the
neighborhoods and should thus be used more extensively. The methodology expanded
the available knowledge on the birth profile in the city, showing potential for
orienting measures devoted to specific geographic areas.
PMID- 9658223
TI - Evaluation of the level of knowledge about visceral leishmaniasis in endemic
areas of Maranhao, brazil
AB - A prospective study was performed to identify knowledge concerning visceral
leishmaniasis (VL) in endemic areas of Maranhao, amongst the rural population of
the Codo township and in a peripheral urban area (an old settlement, Maracana, on
the outskirts of the city of Sao Luis, and Vila Nova/Bom Viver, Paco do Lumiar
township). A total of 283 persons were interviewed, including 53 from Maracana,
103 from Vila Nova/Bom Viver, and 127 from Codo. The sites presented favorable
conditions for the development and maintenance of VL. Some 93.8% of those
interviewed had heard of kala-azar. In Maracana, 50.9% referred to sandflies as
responsible for the transmission of VL, while 87.2% knew that dogs are the main
link in the epidemiological cycle of the disease. Some 77.8% of those interviewed
did not know how to control the disease. As regards manifestations of the
disease, they largely associated it with fever, anemia, weight loss, and an
enlarged abdomen. Only five individuals knew that Glucantimeis used to treat VL.
We conclude that knowledge is poor with regard to all aspects of VL in both the
rural and peripheral urban area.
PMID- 9658224
TI - An epidemiological profile of drug abuse among elementary and high school
students in the Cuiaba public school system, brazil, 1995
AB - A cross-sectional survey was conducted on a sample of 1,061 students to determine
the epidemiological profile of drug abuse among elementary and high school
students in the State public school system in Greater Metropolitan Cuiaba, Mato
Grosso, Brazil, in 1995. Results showed drug abuse among both male and female
students (27. 2% and 24.1%, respectively). Drug abuse was more common in students
over 18 years of age (27.1%), with grade/age discrepancies (70.7%), with higher
classroom absenteeism (44.6%), and with higher social economic levels
(A+B=34.5%). The most frequently abused drugs among male students were alcohol
(81.8%), solvents (18.6%), and marijuana (6.0%). Early alcohol abuse was also
common (12.1 +/-3.6 years). In addition to alcohol (78.6%) and tobacco (29.0%),
the substances most commonly consumed by students were solvents (14.9%),
anxiolytics (6. 0%), and amphetamines (4.8%). The 1995 epidemiological profile of
drug abuse among elementary and high school students in the State public school
system in Cuiaba was similar data from nationwide surveys conducted in 1987,
1989, and 1993.
PMID- 9658225
TI - Blastocystosis in preschool children from bolivar city, venezuela
AB - To evaluate the prevalence of Blastocystis hominis and its clinical relevance,
169 preschool children from the 'Los Coquitos' nursery school living in Bolivar
City, Venezuela, were studied. Stool samples were obtained and examined by direct
microscopic examination, and the Faust and Willis concentration techniques. Some
72 of the children had intestinal parasites, of whom 32 (29.09%) had B. hominis.
Prevalence for the latter was 18.93 % +/- 5.93 %. No differences were observed by
sex or age (X(2) = 1.84 DF= 3; p > 0. 05). In the majority (53.13%) of the
children, B. hominis was the only parasite. Giardia lamblia was the parasite most
frequently identified with B. hominis (39.13%). In 1994, in 12% of the cases more
than five microorganisms per microscopic field were observed. Clinical
manifestations were observed in 70.58% of the preschool children. Presence of
parasites was not correlated with symptomatology, but only with severity. Proper
clinical and parasitological response to treatment was observed in 80% and 90% of
patients, respectively. The conclusion was that B. hominis is a relatively
frequent intestinal parasite among the preschool children evaluated.
PMID- 9658226
TI - Epidemiological control of tuberculosis in pelotas, rio grande do sul, brazil:
treatment compliance
AB - This study assesses risk factors for treatment noncompliance by patients
registered with the Tuberculosis Control Program who live in the urban area of
Pelotas, Rio Grande do Sul State. The study lasted from June 1994 to December
1995. All new cases diagnosed as pulmonary tuberculosis in the 20-80-year age
bracket were monitored by the Tuberculosis Unit, hub of the tuberculosis control
program in Pelotas. All patients was monitored from time of diagnosis through end
of treatment, six months later. Patients answered a standard questionnaire. From
June 1994 to June 1995, 152 cases were recorded, with some 20% treatment
noncompliance. We observed no significant association between noncompliance and
employment status for head-of-family, age, gender, alcoholism, or presence of
symptoms, while the only risk factor significantly associated with noncompliance
was non-white skin color, probably due to the study's weak power as a function of
sample size.
PMID- 9658228
TI - Self-inflicted violence: a sociological concern and a public health problem
AB - This paper has two objectives. The first is to reflect on the meaning of suicide
as a sociological issue, commenting on an article by E.D. Nunes (1988) on the
famous work by Durkheim. The second is to discuss the same issue within the field
of public health, analyzing the contributions by the father of sociology and
approaches by the fields of epidemiology, psychology, psychiatry, and
psychoanalysis, highlighting the work of Brazilian authors. The paper presents
information on the Brazilian epidemiological context and concludes by
demonstrating that only from an analytical point of view can violent causes as a
whole can be studied separately. Thus, they constantly require epistemological
and epidemiological surveillance to construct indicators capable of contributing
to change. This is all the more true because data on current violence need to be
viewed within the context of the social crisis and changes Brazil is undergoing.
PMID- 9658229
TI - The socio-cultural impact of the family health program: an evaluation proposal
AB - This paper develops a critical analysis of the implications of defining the
family as an object of intervention in health, taking as reference case the
Family Health Program and proposing an evaluation of its socio-cultural impact.
As a strategic space for manifestation, confrontation, and therefore observation
of the health-illness process, the family requires a multidisciplinary approach
to its structure, dynamics, and behavior in the face of health-related problems,
determinants, and actions. We present a proposal for assessment of the Family
Health Program based on the premise that problems and practices in the health
field are socio-culturally determined.
PMID- 9658230
TI - Child and adolescent labor: factors, legal aspects, and social repercussions
AB - Children and youth are currently one of the population segments most heavily
jeopardized by the worsening of social, economic, and cultural problems in
Brazil. Factors such as lack of government support for a sound, universally
accessible school system, income concentration, low wages, unemployment, and
family dysfunction have direct impacts on the life histories of children and
adolescents, forcing them to join the labor market early, where their rights as
'citizens with special developmental conditions' are routinely ignored. This
article aims to provide support for the eradication of child labor and the
adaptation of adolescent labor to the terms of the pertinent Brazilian
legislation. To this end, the article reviews the Federal Constitution,
Consolidated Labor Laws, and Statute for Children and Adolescents to analyze
situations in which work activities may or may not be allowed for children and
adolescents, settling possible points of disagreement between the three legal
texts and analyzing their social aspects.
PMID- 9658231
TI - Investigation of a food-borne outbreak in belo horizonte, brasil
PMID- 9658232
TI - On durkheim, dolly, and others dinosaurs: the museum of grand novelties. A
contribution to the debate on the article by everardo duarte nunes
PMID- 9658233
TI - Hepatitis B associated with an alternative therapy centre: look back is extended
to include hepatitis C.
PMID- 9658234
TI - Hepatitis B and C in the second issue of Communicable Disease and Public Health.
PMID- 9658235
TI - [Activity: indicator of quality of health].
PMID- 9658236
TI - [Strain-gauge plethysmography in angiopathies caused by vibrant tools].
AB - The authors compare the results obtained from the strain gauge plethysmography on
79 patients affected by vibrating machines angiopathology with a group of 20
others non exposed to vibrations. The results, analyzed according to the
microcirculation vision, lead the authors to suppose that the damage caused by
vibrating instruments is revealed at the capillary bed trophic exchange level.
PMID- 9658237
TI - Work and chronic health effects among fishermen in Chioggia, Italy.
AB - OBJECTIVES: To evaluate whether there is an association between deep-sea fishing
and common chronic disease. METHODS: The study was cross-sectional,
simultaneously considering groups of fishermen and non-fishermen. Information on
life-style and work was collected by means of questionnaires, and clinical data
were collected by specialists in: Internal Medicine (general clinical
examination), Cardiology (ECG, measurement of arterial pressure), Pneumology
(measurement of spirometric volumes), ENT (clinical examination of the ear, nose
and throat, including audiometry), Ophthalmology (examination of lens). Beside
the common statistical methods, the logistic stepwise regression analysis was
used in order to find the risk factors of the diseases, and to correct the risk
estimates for the confounding variables. RESULTS: Fisherman had prolonged hours
of continuous work, which were found to be correlated with high cigarette and
alcohol consumption. Significant associations were found between, on the one
hand, work accidents, noise-induced hearing loss, solar keratosis, cataracts,
obstructive bronchitis, rhino-sinusitis, otitis media with tympanic perforation,
ECG alterations, and, on the other hand, various aspects of fisherman occupation,
mainly fishing in high sea and work duration as fisherman. CONCLUSION: Deep-sea
fishing is a stressful and risky work; a reduction in the number of years at sea
with reduced exposure to noise, poor weather conditions and sun, and a lower
consumption of cigarettes and alcohol might result in fewer skin, eye respiratory
and cardiovascular diseases, and injuries.
PMID- 9658238
TI - The influence of amalgam fillings on urinary mercury excretion in subjects from
Apulia (southern Italy).
AB - The purpose of this study was to assess the role of dental amalgams and diet upon
urinary mercury (U-Hg) excretion. 98 subjects (50 men and 48 women) not exposed
to inorganic mercury, for either occupational or environmental reasons, and
living in coastal and inland districts of Apulia (Southern Italy) were
considered. All the subjects were administered a questionnaire with questions
concerning life style, medical history, and occupational activity. Dental
amalgams were evaluated with respect to their number and their surface areas.
Urinary mercury was measured by the cold vapour atomic absorption technique.
Expressed in terms of arithmetic mean, U-Hg excretion was found to amount to 1.03
micrograms/g creatinine (5th and 95th percentile: 0.31 and 2.40; range 0.30
3.25). Multiple linear regression analysis showed that, of the several tested
independent variables (dental amalgams, age, body mass index, consumption of
tuna, bass, swordfish, etc.), only the number of amalgam fillings (T = 5.25; p =
0.025) and the number of restored surfaces (T = 2.33; p = 0.020) were found
liable to affect urinary mercury excretion in a significant manner. In
conclusion, the results of this study confirm the primary role of amalgam
fillings in affecting urinary mercury excretion in those subjects who are not
occupationally exposed to inorganic mercury, The resulting urinary mercury levels
can no doubt be taken as the reference values for the population of Apulia.
PMID- 9658239
TI - [Use of the Total Quality strategy in the educational process of the occupational
medicine specialist].
AB - The formative process of the Occupational physician: a Total Quality approach.
There is a growing interest in applying the concepts of Total Quality Management
to the fields of health care and medical education. This paper analyses the field
of occupational medicine education to explore the relationships of teaching and
delivering a product or a service. Issues such as defining teaching customers,
addressing customer's needs, teaching processes, assessing and improving quality
teaching are described. The occupational physician is requested to act according
to particular competencies. This implies the need to meet specific requirements.
To assure the achievement of these goals, the implementation of a teaching
process must include: (i) targeting the learning objectives (knowledge, skills
and attitudes the specialist should have), (ii) planning the evaluation system
(ability of the course to assure the objective achievement), (iii) evaluating the
curriculum (compliance of the acquired competencies to the needs).
PMID- 9658240
TI - [Ergonomic evaluation of the physical tasks in "precision fusion" operations].
AB - In the present paper we performed an "on-site" ergonomic analysis of the work
tasks in in-plant industrial workers. Specific work cycles have been identified
and analysed. We measured spatial and temporal parameters of the different
actions performed by the workers, and we then defined the related risk levels
according to the internationally accepted guide-lines. The results obtained
indicate the need of an ergonomic intervention with the aim of providing
structural changes in the work station.
PMID- 9658241
TI - [Benzene pollution in the city of Bari].
AB - The Authors reported data of benzene concentrations obtained in Bari during
period of time between 1990 and 1995; the measured levels of benzene
concentrations are not in accord with referent values prescribed by the law,
mostly always they are exceeded. Present study also discuss problems related to
gasoline consumption and the number of cars in circulation.
PMID- 9658242
TI - [Results of motor rehabilitation of patients with pseudobulbar syndrome].
AB - The aim of this study was to determine whether rehabilitation treatment has a
real effect on the functional capacity of patients with pseudobulbar syndrome
(SP), and whether there is any difference in efficacy between rehabilitation
treatment initiated as early as possible following stroke, compared to treatment
initiated some months after the last occurrence. We studied 50 SP patients
divided into three groups according to time passed since the last stroke: group
1, 20 patients, less than 180 days after stroke; group 2, 30 patients, more than
180 days after stroke, At the end of the rehabilitation treatment, there was an
improvement in motility (p < 0.005), functional capacity (p < 0.001) and
reduction in disability (p < 0.001) only in group 1. We attribute this result to
the specific pathological substrate of the syndrome and its chronic-progressive
course, which would seem to hinder the action of compensatory mechanisms involved
in late recovery.
PMID- 9658243
TI - [Technical note: proposal of a routine method of accurate measurement of urinary
trans,trans-muconic acid].
AB - A method for routine measurement of urinary trans,trans-muconic acid. A method is
proposed which allows the accurate determination of urinary trans,trans-muconic
acid (Ma) by HPLC with UV detection. Sample pretreatment consists of a first
purification on strong anionic exchange (SAX) cartridges followed by extraction
on "end capped" reversed-phase (C18-EC) ones. Purified samples are directly
injected onto a chromatographic column (C18, 150 x 4.6 mm I.D., 3 microns) which
is eluted with water: methanol: acetic acid (97:2:1, v/v) mixture followed by a
"spike" of acetonitrile. The retention time of MA is 15 min, the coefficient of
variation is lower than 3%, the limit of detection is 7 micrograms/l. The method
seems suitable for accurate biological monitoring of subjects exposed to benzene.
PMID- 9658244
TI - Immunizations for international travel.
AB - Immunization recommendations for international travelers is a complex subject
that takes into consideration the geographic destination, planned activities
during travel, health conditions at destination, length of trip, and underlying
health status of the traveler. The final immunization program is also determined
by how much time is available before departure and the worldwide availability of
vaccines and their cost. In some cases, preventive behaviors and chemoprophylaxis
may protect against the risk of infection when immunizations are unavailable or
unobtainable.
PMID- 9658245
TI - Malaria in travelers. Epidemiology, disease, and prevention.
AB - The combination of increases in international travel and escalating drug
resistance has resulted in a growing number of travelers contracting malaria.
Preventing malaria-associated morbidity and mortality will require improved
health information for travelers about the risk of malaria and appropriate
preventive measures, improved recognition of infection by physicians, rapid and
accurate laboratory diagnosis, and prompt initiation of effective therapy.
PMID- 9658246
TI - Travelers' diarrhea. Epidemiology, prevention, and self-treatment.
AB - Risk factors for travelers' diarrhea include adventurous behavior, consumption of
unclean water or food, and special hosts like those taking long acting H2
blockers. Approaches to prevention include education about risk factors, which
often fails to lead to modification of risky behavior, and chemoprophylaxis with
bismuth subsalicylate-containing compounds or antimicrobial agents.
Chemoprophylaxis is generally discouraged except in special circumstances and in
high-risk hosts. Self-treatment of travelers' diarrhea is successful in limiting
the course of diarrhea and minimizing losses of vacation and business time.
Current therapeutic options, in order of increasing effectiveness, include
attapulgite, BSS-containing compounds, loperamide, antimicrobial agents such as
the fluoroquinolones, and the combination of loperamide and an antimicrobial
agent. Under study are a nonabsorbed antimicrobial agent, rifaximin, and a novel
calmodulin inhibitor, zaldaride. Development and evaluation of vaccines against
enterotoxigenic Escherichia coli and Shigella are proceeding apace but are not
yet available for routine use.
PMID- 9658247
TI - Prevention of common travel ailments.
AB - An understanding of the subjects covered in this article is significant in
keeping travelers healthy and comfortable. Each section covers a range of
problems and suggestions for their prevention. The areas that are reviewed are:
1) fitness to fly; 2) problems in transit; 3) altitude sickness; 4) marine and
swimming hazards; 5) insect precautions; 6) pre- and posttravel care; and 7)
illness abroad. An effort has been made to provide practical recommendations as
in many cases there is little data and no rules, thus the travel health advisor,
with the patients' input, will need to determine the best course of action for
each individual and itinerary.
PMID- 9658249
TI - Travel with infants and children.
AB - The risks faced by children traveling internationally may be minimized by
providing and applying advice about comfort, safety, skin protection, and food
and water hygiene. Prior to travel, children should be current on standard
immunizations and may receive several specialized vaccines. Antibiotics for the
presumptive treatment of travelers' diarrhea are usually indicated, and malaria
chemoprophylaxis may be safely administered even to young children. Evaluation
and care following prolonged stays in foreign countries can decrease the burden
of imported disease.
PMID- 9658248
TI - The pregnant traveler.
AB - The care of the pregnant traveler is both challenging and rewarding. It requires
clinical information and skills that are derived from many disciplines. This
article reviews preparatory guidelines for safe travel by the pregnant mother and
her most important travel companion, the developing fetus. Issues considered are
pretravel risk assessment, immunizations, and prevention of travelers' diarrhea
and hepatitis. The safety and efficacy of malaria chemoprophylaxis in the present
context of widespread multidrug-resistant malaria is discussed, and guidelines
are offered for both prevention and treatment. A safety profile of commonly used
travel medications, antibiotics, and antiparasitic drugs is reviewed.
PMID- 9658250
TI - The compromised traveler.
AB - Compromised travelers represent a diverse and challenging group of individuals.
They include HIV-infected patients who are at risk for potentially adverse
reactions to immunizations, and new exposures to enteric water-borne
opportunistic pathogens associated with chronic infections. Such travelers may
encounter unfamiliar opportunistic fungi and classical tropical infections, such
as leishmaniasis, whose pathogenesis can be enhanced by the presence of prior HIV
infection. Other immunocompromised groups include those who are functionally or
anatomically asplenic, and patients who are iatrogenically immunosuppressed from
medications utilized for solid organ transplantation, chemotherapy, or treatment
of malignancies. This population of travelers also includes those with diabetes
mellitus who may require adjustments in their dosing, administration, and
possibly even the types of insulin used on their trips. These patients are also
at greater risk for acquisition of tuberculosis, severe community-acquired
pneumonia, urinary tract infections, and pyomyositis. Older travelers present
both the infectious disease and travel medicine specialist with issues such
events, malignancy-related infections, myocardial infarction, and other forms of
cardiopulmonary compromise, which the authors address in this article.
PMID- 9658251
TI - The sexual health of travelers.
AB - Sex and travel do not infrequently coincide as pleasurable occupations. This
articles explores the possible risks of unsafe sexual activity in a travel
related context, gives guidelines on how to decrease risks for both partners, and
outlines how to manage the exposed or infected traveler on his or her return
home. Both sexually transmitted infections and contraception are covered.
PMID- 9658252
TI - Screening returning travelers.
AB - Posttravel screening is the clinical and laboratory assessment of an individual
aimed at uncovering occult infections, pathology, or health risks, the treatment
of which will yield a significant health benefit to the individual. Screening
must be tailored to the different risk patterns associated with different travel
categories (e.g., missionary, tourist). Screening, predominantly a secondary
prevention strategy, is most cost-effective when integrated with primary
prevention strategies aimed at preventing future travel related illness (Table
6). The screening process begins with a medical history that allows a definition
of risks and a tailored approach to laboratory tests. The screening tests
currently available for STDs, tuberculosis, and parasitic infections have been
reviewed, and although cost-effectiveness data are not available for most post
travel screening tests, recommended approaches are proposed. Traditionally,
screening has been directed at uncovering occult infectious disease (STDs,
tuberculosis, and parasitic infections). Important benefits can be gained,
however, by including screening questions and tests for those diseases that are
the major causes of mortality, both in nontraveling and in traveling North
Americans, that is, the atherosclerotic and neoplastic diseases and trauma,
especially vehicular.
PMID- 9658253
TI - Fever in the returned traveler.
AB - The most important cause of fever in the returned traveler is malaria. All
febrile patients in which malaria is epidemiologically possible require urgent
evaluation for P. falciparum malaria, which can be rapidly fatal in the nonimmune
patient. Early diagnosis and therapy can prevent severe morbidity and mortality.
Other less common causes of undifferentiated fever include acute schistosomiasis,
the enteric fevers, rickettsial diseases, leptospirosis, and dengue fever. Early
empiric therapy for suspected leptospirosis and the rickettsial infections is
encouraged to decrease morbidity and mortality. About a quarter of febrile
patients do not have an etiologic agent determined for their illness but recover
without sequelae. Patients with fever and hemorrhagic manifestations within 3
weeks of their return need to be isolated for the remote possibility of a highly
transmissible agent. Although the febrile traveler is always a challenge, the
real world differential diagnosis is limited and a systematic approach via the
history, physical examination, and selected laboratory tests is usually
sufficient to confirm the diagnosis or eliminate potentially serious infections.
PMID- 9658254
TI - Skin problems in the traveler.
AB - Skin lesions are common in travelers and include a mix of mundane dermatologic
problems and rare diseases acquired only in remote or tropical regions. The
morphology, distribution, and progression of the lesions are useful in assessing
possible causes. Early in the evaluation it is important to determine whether the
patient might have a process that is rapidly progressive, treatable, or
transmissible. In addition to routine laboratory studies, biopsy and serologic
tests are often necessary to confirm a specific diagnosis.
PMID- 9658255
TI - Persistent diarrhea in the returned traveler.
AB - In conclusion, the causes of chronic diarrhea in the returned traveler are
protean. Careful evaluation requires an understanding of where the traveler has
been, when they were there, the type of diarrheal illness, medications taken, and
knowledge of the patients' other medical problems. Protozoa, particularly G.
lamblia, C. parvum, and C. cayatenensis, are among the more commonly identified
agents. If the patient is immunocompromised, microsporidia and Isospora become
more likely, and a prior history of antimicrobial use raises the possibility of
C. difficile colitis. Occasionally helminths, which establish intimate contact
with the intestinal mucosa, may also cause prolonged diarrhea. If these and other
gastrointestinal insults, such as tropical sprue, small bowel overgrowth, lactose
intolerance, and processes unrelated to travel are excluded by more invasive
studies or clinical history, the patient can be reassured that idiopathic chronic
diarrhea is usually self-limited.
PMID- 9658256
TI - Eosinophilia in the returning traveler.
AB - Eosinophilia is one of the most common laboratory abnormalities seen in the
returning traveler. Although elevations in peripheral eosinophil levels can occur
in a wide variety of disease processes, worldwide, helminth parasites are the
major group of infectious agents responsible for eosinophilia. While often
directed at helminth infections in their early stages of clinical evolution, the
approach to the evaluation of the returning traveler with eosinophilia must
consider the many causes of eosinophilia including those not casually related to
travel. This article reviews the major parasitic causes of eosinophilia and
provides a systematic approach to the evaluation of eosinophilia following
travel.
PMID- 9658257
TI - The ethnic minority traveler.
AB - Although the ethnic minority traveler is exposed to the same risks as other
travelers, there are special considerations that make them vulnerable to certain
diseases. In addition, many ethnic minority travelers are traditionally
underserved by the medical community and often travel without the benefit of
adequate counseling and immunization. The specific disease entities covered in
this article include parasitic diseases (e.g. malaria, trypanosomiasis,
intestinal helminths), tuberculosis, and other respiratory diseases, dengue, and
sexually transmitted diseases and HIV.
PMID- 9658258
TI - Keeping current. Travel medicine resources available on the Internet.
AB - As travel medicine practices expand and multiply, practitioners increasingly need
to be familiar with constantly changing disease epidemiology and drug resistance
patterns in over 220 different countries. Nowadays, keeping current means
utilizing the wide array of resources available on the internet. This article
contains background information on the most relevant travel medicine-oriented
Internet sites and provides their universal resource locators in a convenient
table.
PMID- 9658259
TI - Vascular dementia: dead or alive?
AB - The term 'Vascular Dementia' remains popular as a diagnostic entity, since it
encompasses a variety of vascular pathologies. This is in stark contrast to many
clinical classificatory systems that weight their definitions strongly towards
stroke alone. A diagnosis of vascular dementia is complicated by compounding
factors that reduce both the validity and specificity of diagnostic systems. This
review highlights some of the problems faced in epidemiological, clinical,
neuropathological and radiological studies attempting to define a clear-cut
syndrome of dementia associated with cerebrovascular disease. The role of non
stroke ischaemia is also discussed. It is concluded that the term vascular
dementia may have outlived its usefulness as a valid concept; alternative
approaches are suggested.
PMID- 9658260
TI - The mini-mental state examination, will we be using it in 2001?
PMID- 9658261
TI - Mini-mental and son.
PMID- 9658262
TI - An informant interview for the diagnosis of dementia and depression in older
adults (IDD-GMS).
AB - BACKGROUND: There has been no instrument developed for the differential diagnosis
of psychiatric conditions using an informant. The present study describes the
development and validation of an informant interview for the diagnosis of
dementia and depression in older adults (IDD-GMS). The IDD-GMs, as its name
indicates, is based upon the well-established Geriatric Mental State Schedule
(GMS). METHOD: Thirty older adults with psychiatric illnesses were identified. An
informant/career was interviewed using the IDD-GMS. Questions from the GMS were
altered to reflect the informant nature of interview. Validity was compared to
ICD-10 diagnoses. Interrater reliability was determined. RESULTS: Using a
hierarchical diagnostic system, receiver operating characteristics demonstrated
one optimal cutpoint for sensitivity, > 13 for dementia and > 16 for depression,
and one for specificity, > 13 for dementia and > 10 for depression. CONCLUSION:
The validity and reliability of the IDD-GMS falls within acceptable limits and
indicates that the IDD-GMS can be used as a diagnostic instrument for dementia
and depression. The IDD-GMS represents the first informant interview to achieve
this.
PMID- 9658263
TI - Psychosocial factors associated with the use/non-use of mental health services by
primary carers of individuals with dementia.
AB - The study investigated psychosocial factors associated with the use/non-use of
services by primary carers of people with dementia (caring for relative/friend
with dementia). The factors considered were individual differences, health,
stress, family/social support, years of caring, age of carers/person with
dementia, gender and level of behavioural disturbance presented by the person
with dementia. The participants were referred to the study by health services,
social services representatives and GPs. The carers (N = 50) were divided into
two groups (service user/non-user). The findings indicated that primary carers in
the non-user service group scored significantly higher on a measure (sense of
coherence; SOC) estimating an individual's ability to deal with stressful
situations. The individual's ability to deal with caring responsibilities was
associated with a reduction in the level of diagnosable psychiatric disorder or
'caseness' and the non-use of services. None of the other factors considered were
found to be significantly different between the two career groups. However, a
significant inverse association between health, stress and individual ability to
deal with stressful situations was found when the two career groups were
combined.
PMID- 9658264
TI - Does post-traumatic stress disorder occur after stroke: a preliminary study.
AB - BACKGROUND AND PURPOSE: Psychological reactions after stroke have been recognized
for some time. The present study examined whether psychological symptoms
consistent with post-traumatic stress disorder (PTSD) could occur after stroke as
a consequence of the sudden and unpredictable occurrence of a life-threatening
internal stressor. METHODS: Sixty-one patients who had experienced a first-ever
stroke or transient ischaemic attack were assessed using standard self-report
clinical measures for anxiety, depression and PTSD. Those patients who fulfilled
criteria on at least one PTSD self-report measure were subsequently assessed
using a structured clinical interview for PTSD. RESULTS: Six (9.8%) patients
fulfilled criteria for PTSD. No significant differences were found between the
post-stroke PTSD group and the non-PTSD group in terms of premorbid health and
lifestyle, or experiences of adverse life events. Significant differences were
noted with respect to self-reported post-stroke mental health and premorbid
neuroticism. The post-stroke PTSD group also scored consistently higher on
measures of anxiety, depression and psychiatric caseness. CONCLUSIONS: The
results of this study demonstrate a number of close similarities between post
stroke PTSD and classical PTSD. We therefore conclude that PTSD or a PTSD-like
syndrome can occur after stroke.
PMID- 9658265
TI - Younger people with dementia: diagnostic issues, effects on carers and use of
services.
AB - OBJECTIVE: To determine difficulties experienced by carers of younger people with
dementia. DESIGN: Cross-sectional questionnaire survey. PARTICIPANTS: 102
eligible carers of persons less than 65 years of age with dementia, recruited
through support groups and clinicians' referrals. MAIN OUTCOME MEASURES: Problems
with diagnostic process; professionals/services consulted; psychological,
physical, occupational and financial impact of illness on carers and children;
use of and satisfaction with services. MAIN RESULTS: Diagnostic problems were
reported by 71% of carers. Mean time until diagnosis was 3.4 years (SD 2.8) after
consulting 2.8 (1.4) professionals. Carers reported frustration (81%) and grief
(73%). Adverse psychological effects were common, more so in female than male
carers (p < 0.01). The younger the carer, the more psychological and physical
effects were experienced (p < 0.01). Only 8% of carers considered that their
children had encountered no problems because of the dementia. Of 61 working
carers, 59% reduced their hours or stopped working after diagnosis, and 89% of
all carers had experienced financial problems subsequent to diagnosis. Most
carers (89%) had used a support service, but 25% had never used community
support, 32% had never used respite. Proportions of carers rating services as
good ranged between 43 and 100%. CONCLUSIONS: Younger people with dementia, and
their carers, face difficulties in obtaining a diagnosis. Carers also experience
psychological problems, financial worries, loss of employment and family
conflict, and their children are affected. Most carers had used services, but
some dissatisfaction existed.
PMID- 9658266
TI - Assessment of progression and prognosis in 'possible' and 'probable' Alzheimer's
disease.
AB - OBJECTIVE: The objective of this study was to assess the rate of progression and
clinical predictors of decline in subjects with possible and probable Alzheimer's
disease (AD). DESIGN/SETTING: The annual rate of change (ARC) for
cognitive/functional scales was calculated for 95 subjects with AD attending a
memory clinic. Two consecutive ARCs were calculated for a subgroup of 39
subjects. RESULTS: The ARCs were relatively normally distributed; however, there
was a large degree of variability. Neither age nor duration of symptoms at
presentations were predictive of the rate of decline. However, the data suggested
an effect of gender, with males having a greater rate of decline in cognition (p
= 0.02). Finally, the rate of progression over the first year did not predict the
subsequent ARC (p = 0.25). CONCLUSIONS: The high variability in ARCs observed in
this study and poor correlation between consecutive ARCs suggest that neither
mean ARC values nor the previous rate of decline can be used to aid clinicians in
the assessment of response to acetylcholinesterase inhibitors or other specific
treatments for AD.
PMID- 9658267
TI - Concurrent validity of the GMS-AGECAT (A3) package in a Danish nursing home
population.
AB - AIM: To validate the Danish version of the GMS-AGECAT (A3), the Standardized Mini
Mental State Examination (SMMSE) and the Geriatric Depression Scale-15 (GDS-15)
by comparing them to clinical ICD-10 criteria in a Danish nursing home
population. METHODS: With a participation of 91%, the study included 100
residents. All residents were interviewed with the GMS-AGECAT (A3), SMMSE and GDS
15 by an MD and then blindly diagnosed by a consultant geriatric psychiatrist.
All residents approached for an interview were included, also those who were not
able to communicate (the non-accessibles). RESULTS: The prevalence of clinical
psychiatric ICD-10 main diagnoses was 56%. The non-accessibles had significantly
higher psychiatric morbidity and lower ADL scores (modified Barthel ADL index)
compared to those who were able to communicate. With the non-accessibles (N =
100) included, the optimal screening and diagnostic cutpoint for the GMS-AGECAT
organic diagnoses was 2/3, with 96% sensitivity, 73% specificity, 77% predictive
value of a positive test and 95% predictive value of a negative test. The SMMSE
and GDS-15 had better screening properties compared to the GMS-AGECAT but only
60% of the residents were able to complete the SMMSE and 78% were able to
complete the GDS-15. CONCLUSION: The Danish version of the GMS-AGECAT has
relevant diagnostic and screening properties for organic disorders in Danish
nursing home populations.
PMID- 9658269
TI - Current awareness in geriatric psychiatry.
PMID- 9658268
TI - Serotonin syndrome following the administration of tramadol with paroxetine.
PMID- 9658270
TI - Do consultant home visits have a future in old age psychiatry?
PMID- 9658272
TI - The validity of psychometric instruments for detection of dementia in the elderly
general population.
AB - OBJECTIVE: To compare the validity of different instruments for screening and
diagnosis of dementia and to provide threshold scores for these purposes, ie
screening focusing on a high sensitivity and diagnosis focusing on a high
specificity. SETTING: 287 subjects from a general population sample who had
completed more than one of these psychometric tests. METHODS: The performances of
the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type,
Multi-Infarct Dementia and Dementias of Other Aetiology according to ICD-10 and
DSM-III-R, the Mini-Mental State Examination, the Blessed Dementia Rating Scale,
the Global Deterioration Scale, the Verbal Fluency Test, the Word list Learning
Task, the Trail Making Test and the Labyrinth Test were compared using receiver
operating characteristics analysis. RESULTS: The validity of composite
instruments for the discrimination of dementia and cognitive health was higher
than the validity of individual tests. However, some cognitive tests, ie verbal
fluency and immediate recall of words, reached a high validity, making them
useful and short screening instruments for dementia. CONCLUSION: There is no
perfect instrument for screening and diagnosis of dementia. Different threshold
scores for different purposes were provided in the present study. Recommendations
for improving the validity of the Delayed Word List Learning Task for
discriminating dementia and cognitive health include the expansion of list length
and shortening of delay.
PMID- 9658271
TI - Depressive symptoms of Alzheimer caregivers are mainly due to personal rather
than patient factors.
AB - OBJECTIVES: To investigate the predictors of caregiver's depressive symptoms in a
sample of community-dwelling Alzheimer's patients. DESIGN: A cross-sectional
study was conducted in an Alzheimer's unit specifically devoted to the care of
demented patients in Brescia Province (Italy). One hundred and three dyads were
consecutively recruited between July 1994 and July 1995. Caregivers were
sons/daughters (65%) or husbands/wives; mean age was 54.6 +/- 13.2. Alzheimer's
patients Mini Mental State Examination score was 11.3 +/- 8.3; patients were
equally distributed among disease severity levels. The following variables have
been collected: (a) background and context variables (caregiver's age, gender,
marital status, education, relationship and cohabitation with the patient,
employment status, satisfaction with household income);(b) caregiver's personal
resources (health, social relationships and social interactions, formal supports
use, assistance and vigilance); (d) primary stressors (patient's age and gender,
cognitive status, functional status, frequency of behavioural disturbances).
Caregiver's depressive symptoms represented the main outcome measure. RESULTS:
Being husband or wife, low self-rated health and caregiving competence, high
numbers of hours for assistance and patient's behavioural disturbances and
younger age were associated caregiver's depressive symptoms. With multivariate
analysis only relationship to the patient, caregiver's health and competence were
independent predictors of caregiver's depressive symptoms. CONCLUSION: Factors
related to the caregiver--relationship, health and competence--rather than to the
patient constitute the main risk factors for caregiver's depressive
symptomatology.
PMID- 9658273
TI - CANDID--Counselling and Diagnosis in Dementia: a national telemedicine service
supporting the care of younger patients with dementia.
AB - OBJECTIVES: To audit and evaluate the introduction of a novel support service for
younger people with dementia, their families and the professionals caring for
them. DESIGN: A retrospective review of all calls received by a telephone
helpline over a 2-year period. SETTING: CANDID (Counselling and Diagnosis in
Dementia) offers direct access, by telephone and e-mail, to specially trained
nurse/counsellors who record the caller's query, provide emotional support and
practical advice. In addition to general advice, clinical details are held for
patients registered with the service so that the advice given can be tailored to
the patient's specific need and routed via the general practitioner for action.
Advice is reviewed by a consultant neurologist and psychiatrist. SUBJECT: Callers
to the CANDID helpline, who made a total of 1,121 calls. MAIN OUTCOME MEASURES:
Details of the caller and of the patient they were caring for. Reason for calling
and advice given to the caller RESULTS: Of the 1,121 calls received during the
first 2 years of operation, 547 were 'registered' calls relating to 241
individual patients where more specific advice could be given through the GP. The
remaining 574 'generic' calls were from members of the public and healthcare
professionals who had heard about the service and were seeking information and
advice. Reasons for calls were divided into three broad categories: general
information; clinical advice; and advice on social issues. Among the registered
callers, 50% of calls were for clinical advice. Letters were sent to GPs on 67
occasions; 48 (56%) provided information only for the GP, 16 (24%) advised a
secondary referral and eight (12%) advised on the use of specific medication.
CONCLUSION: The service has become rapidly accepted and used by families of
patients and members of the public. Healthcare professionals have made less use
of the service than anticipated, but it is hoped that this will increased as
information about the service becomes disseminated.
PMID- 9658274
TI - A preliminary report: a new scale to identify the pseudodementia syndrome.
AB - BACKGROUND: The literature was reviewed to abstract items which were claimed to
distinguish organic dementia from pseudodementia. Their discriminating powers
were tested in a prospective study. Eighteen of these items were selected to
create a questionnaire which should distinguish organic dementia from
pseudodementia. The gold standard was the final diagnosis given by a consultant
psychiatrist 12-14 months later. METHOD: One hundred and twenty-eight patients
referred to our service with a differential diagnosis of depressive
pseudodementia were screened using a checklist of 44 characteristic features (in
the form of questions with 'yes' or 'no' answers) which were claimed in the
literature of differentiate between organic dementia and depressive
pseudodementia. This checklist covers the areas of history, clinical data,
insight and performance. RESULTS: Forty points (questions) out of the 44 in the
checklist showed significant discriminating power to differentiate dementia from
depressive pseudodementia (p < 0.01). A principal component and factor analysis
was performed from which 18 questions were extracted. The shortened questionnaire
was able to classify (43/44 cases) 98% of dementia cases and (60/63) 95% of
depression correctly. A new definition has been introduced for 'pseudodementia'
as a syndrome of reversible subjective or objective cognitive problems caused by
non-organic disorder. Thus depressive pseudodementia may be classified into two
subtypes. Type I is a group of patients who have depressive symptoms with subject
complaint of dysmnesia without measurable intellectual deficits. Type II is a
group of patients who have depressive symptoms and show poor cognitive
performance based on poor concentration not due to organic disorder.
PMID- 9658275
TI - Cognitive impairment in late life schizophrenia: a suitable case for treatment?
AB - The benign side-effect profiles of the atypical antipsychotic drugs have earned
them an important niche in old age psychiatry. Evidence for a specific
improvement in cognitive function associated with the use of these drugs is
inconsistent and the definitive studies are still awaited. If these drugs can
improve cognitive function in elderly patients with schizophrenia and
schizophrenia-like psychosis, then in terms of patient-years of effective
treatment of cognition, this action may be more significant than the treatment of
Alzheimer's disease with cholinergic therapies.
PMID- 9658276
TI - Assessment of patients with memory problems using a nurse-administered instrument
to detect early dementia and dementia subtypes.
AB - BACKGROUND: With the development of pharmacological treatments for Alzheimer's
disease there will be an increase in the numbers of patients requiring assessment
from specialist services. Could the role of the specialist clinician be supported
by other health professionals screening those who might benefit from treatment?
METHOD: Sixty-four consecutive referrals to the Leicester University Memory
Clinic were assessed at home by a community psychiatric nurse using a semi
structured interview. The nurse then reported her findings to a psychiatrist and
a diagnosis was agreed. This diagnosis was then compared to the Memory Clinic
diagnosis and a standardized (ICD-10) diagnosis recorded by another psychiatrist
examining the clinic records. RESULTS: The nurse assessment procedure performed
well in detecting dementia, with a kappa statistic (k) of 0.75 when compared to
the standardized and Memory Clinic diagnoses. There was, however, only moderate
concordance between the ICD-10 diagnosis and nurse (k = 0.46) and the Memory
Clinic and nurse (k = 0.60) for Alzheimer's disease. The relatively low k value
for Alzheimer's disease was principally a result of difficult in differentiating
vascular dementia. CONCLUSIONS: A single supervised community psychiatric nurse,
using a structured assessment instrument, can adequately detect early dementia in
a sample of patients referred with memory problems. Subtypes of dementia are not,
however, accurately differentiated.
PMID- 9658277
TI - Prevalence and clinical correlates of psychotic symptoms in Alzheimer's disease.
AB - Psychotic symptoms occur commonly in Alzheimer's disease (AD), predict a more
rapid rate of cognitive decline and increase the risk of aggressive behaviour.
Seventy patients with probable AD, recruited from an old age psychiatry service,
were assessed to determine the prevalence and clinical correlates of delusions
and hallucinations. Psychiatric symptoms were measured using the Behavioural
Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Hamilton Rating Scale
for depression (HRSD) and the Depressive Signs Scale (DSS). Thirty-four per cent
of the sample experienced delusions and 11% hallucinations in the previous month.
Men were more likely than women to have experienced psychotic symptoms. Psychotic
and non-psychotic groups did not differ in age, age at illness onset, dementia
severity, HRSD or DSS scores. This study confirms the high prevalence of
psychotic symptoms in AD patients encountered in clinical practice, and suggests
that psychosis and depression represent independent behavioural disturbances in
AD.
PMID- 9658278
TI - Evaluation of three aggression/agitation behaviour rating scales for use on an
acute admission and assessment psychogeriatric ward.
AB - BACKGROUND: In recent years many instruments measuring aggressive and agitated
behaviours among the elderly in a variety of settings have emerged. Individual
instruments have only occasionally been compared with each other. METHOD: Some
psychometric properties of three aggression/agitation scales on an acute
assessment and admission psychogeriatric ward were examined. The correlation
between the Rating Scale for Aggressive Behaviour in the Elderly (RAGE), the
Cohen-Mansfield Agitation Inventory (CMAI) and the Brief Agitation Rating Scale
(BARS) and their internal consistencies and test-retest and interrater
reliabilities were measured. RESULTS: The RAGE was strongly correlated with the
CMAI (rho = +0.73) and the BARS (rho = +0.72). The CMAI was strongly correlated
with the CMAI (rho = +0.84). The internal consistency, as measured by Cronbach's
alpha, was greater than 0.8 on all three scales. The test-retest and interrater
reliability correlations were 0.75 or greater for all three scales (except the
BARS interrater reliability correlation of 0.6). CONCLUSIONS: All three scales
have good psychometric properties for use in acute admission assessment
psychogeriatric wards.
PMID- 9658280
TI - Current awareness in geriatric psychiatry.
PMID- 9658279
TI - SSRI discontinuation syndrome treated with fluoxetine.
PMID- 9658281
TI - Calretinin in pretecto- and olivocerebellar projections in the chick:
immunohistochemical and experimental study.
AB - Calretinin (CaR) is a calcium-binding protein that is distributed extensively in
the central nervous system. It is localized in the cell bodies and neurites of
specific neuronal populations and serves, therefore, as a reliable anatomical
marker. Some components of the pretectocerebellar projection, which connects
specific pretectal nuclei to caudal cerebellar folia, are concerned with the
cerebellar control of visual reflexes. We investigated the distribution of
pretectocerebellar-projecting neurons in relation to cells that show CaR
immunoreactivity. Cells that project to the cerebellar cortex in the diencephalic
primary visual nuclei and in other grisea, like the nucleus spiriformis medialis
and the nucleus dorsofrontalis, colocalized with those that appeared to be
immunolabeled intensely with anti-CaR antiserum. To explore the hypothesis of a
common developmental origin of these pretectal cerebellopetal neurons, we also
investigated the development of CaR-immunopositive cells in the chick pretectum
and the arrival of their fibers in the cerebellum, from 10 days of incubation
(stage 36) to posthatching stages. Finally, we analyzed the source of CaR+
climbing fibers and found a subpopulation of CaR+ cells in the inferior olivary
nucleus. On the whole, these results suggest that there is a common developmental
origin of pretectal cerebellopetal neurons, some of which share the property of
CaR expression. The functional significance of this correlation needs to be
investigated.
PMID- 9658282
TI - Nicotinic acetylcholine receptors in rat cochlear nucleus: [125I]-alpha
bungarotoxin receptor autoradiography and in situ hybridization of alpha 7 nAChR
subunit mRNA.
AB - The cochlear nucleus (CN) is the first site in the central nervous system (CNS)
for processing auditory information. Acetylcholine in the CN is primarily
extrinsic and is an important neurotransmitter in efferent pathways thought to
provide CNS modulation of afferent signal processing. Although muscarinic
acetylcholine receptors have been studied in the CN, the role of nicotinic
receptors has not. We examined the distribution of one nicotinic acetylcholine
receptor subtype, the alpha-bungarotoxin receptor (alpha Bgt), in the CN.
Quantitative autoradiography was used to localize receptors and in situ
hybridization was used to localize alpha 7 mRNA in CN neurons that express the
alpha Bgt receptor. Binding sites for alpha Bgt are abundant in the anterior
ventral, posterior ventral, and dorsal divisions of the CN, and receptor density
is low in the granule cell layer and interstitial nucleus. Heterogeneity in CN
subregions is described. Four distinct patterns of alpha Bgt binding were
observed: (1) binding over and around neuronal cell bodies, (2) receptors locally
surrounding neurons, (3) dense punctate binding in the dorsal CN (DCN) not
associated with neuronal cell bodies, and (4) diffuse fields of alpha Bgt
receptors prominent in the DCN molecular layer, a field underlying the granule
cell layer and in the medial sheet. The perikaryial receptors are abundant in the
ventral CN (VCN) and are always associated with neurons expressing mRNA for the
receptor. Other neurons in the VCN also express alpha 7 mRNA, but without alpha
Bgt receptor expression associated with the cell body. In general, alpha Bgt
receptor distribution parallels cholinergic terminal distribution, except in
granule cell regions rich in cholinergic markers but low in alpha Bgt receptors.
The findings indicate that alpha Bgt receptors are widespread in the CN but are
selectively localized on somata, proximal dendrites, or distal dendrites
depending on the specific CN subregion. The data are consistent with the
hypothesis that descending cholinergic fibers modulate afferent auditory signals
by regulating intracellular Ca2+ through alpha Bgt receptors.
PMID- 9658283
TI - Tumor-suppressor p53 is expressed in proliferating and newly formed neurons of
the embryonic and postnatal rat brain: comparison with expression of the cell
cycle regulators p21Waf1/Cip1, p27Kip1, p57Kip2, p16Ink4a, cyclin G1, and the
proto-oncogene Bax.
AB - The tumor-suppressor protein p53 has been implicated in cell cycle arrest and
apoptotic cell death in dividing cells (Yonish-Rouach et al. [1991] Nature
352:342-347. To elucidate possible functions of p53 in the regulation of cell
division and cell death during development of the rat central nervous system, we
compared the spatial and temporal expressions of p53 mRNA and protein with those
of its transcriptional targets Bax, p21Waf1, and cyclin G1 and with the cyclin
dependent kinase inhibitors p27Kip1, p57Kip2, and p16Ink4a. From embryonic day 14
until the second postnatal week, p53 mRNA and protein were found predominantly in
proliferating zones, including the cells of the emerging external granular layer
of the cerebellum, and the ventricular and the subventricular zones of the
forebrain. At all postnatal ages, there was a high expression of p53 mRNA and
protein in cells of the rostral migratory stream, a well-defined pathway along
which precursor cells of olfactory interneurons migrate from the ventricular and
subventricular zones toward the olfactory bulb. In addition to its expression in
proliferating cell populations, p53 was expressed in postmitotic cells of the
cerebral cortex and hippocampus at embryonic and early postnatal stages. p53,
p27Kip1, p16Ink4a, and bax alpha mRNA colocalized in the ventricular and
subventricular zones at embryonic and early postnatal stages, but the
distribution of p53 differed from that of its transcriptional targets cyclin G1
and p21Waf1 and from that of the cyclin-dependent kinase inhibitor p57Kip2, which
were predominantly expressed in fully differentiated neurons. Double-labeling
studies showed that p53 mRNA and protein were absent in cells undergoing
developmental cell death, as identified by the presence of single- or double
stranded nuclear DNA breaks. Protein levels of p53 decreased during development
in all brain areas studied. These results indicate a role for p53 in the control
of cell division and early differentiation rather than in the control of cell
death during rat brain development. The nonoverlapping temporal and spatial
expression patterns of p53 and its transcriptional targets Bax, cyclin G1 and
p21Waf1 suggest that each of these gene products fulfill independent roles in
brain morphogenesis.
PMID- 9658284
TI - Concomitant expression of genes encoding integrin alpha v beta 5 heterodimer and
vitronectin in growing parallel fibers of postnatal rat cerebellum: a possible
role as mediators of parallel fiber elongation.
AB - External granule cells in the premigratory zone and the upper molecular layer of
neonatal rat cerebellum elongate their neurites (parallel fibers) bidirectionally
before and during migration into the internal granular layer. In the present
study, it is shown that integrin alpha v beta 5 heterodimer (INT alpha v beta 5)
is expressed in parallel fibers in these layers at postnatal days 3-20, but not
in migrating granule cells or mature parallel fibers. Vitronectin (VN), the
dominant ligand for INT alpha v beta 5, was concomitantly detected in the
premigratory zone and the upper molecular layer during this period. Several other
subunits including alpha 1-6 and beta 1-4 were not detected. When granule cells
were prepared from postnatal cerebella and cultured for a few days, the parallel
fibers elongated well in response to VN, but the granule cells did not migrate on
VN. This fiber elongation was specifically inhibited by both anti-INT alpha v
beta 5 antibody and peptides containing Arg-Gly-Asp (RGD), a sequence responsible
for cell adhesion mediated by VN. Neither control integrin antibody against
integrin alpha v beta 3 heterodimer nor control peptides containing Arg-Gly-Glu
(RGE) showed an inhibitory effect on fiber elongation. These observations
strongly suggest that the INT alpha v beta 5 VN receptor plays a role in the
elongation of parallel fibers from granule cells during cerebellar histogenesis,
but its expression is not required for their maintenance or granule cell
migration. INT alpha v beta k could be considered as a new marker of parallel
fibers during cerebellar development.
PMID- 9658285
TI - Terminal dendritic sprouting and reactive synaptogenesis in the postnatal organ
of Corti in culture.
AB - Synaptogenesis in the organ of Corti between the primary receptors, the inner
hair cells, and the peripheral processes of their afferent spiral ganglion
neurons in the mouse lasts for 5 days postnatally (Sobkowicz et al. [1986] J.
Neurocytol. 15:693-714). The transplantation of the organ into culture at the
fifth postnatal day induces a reactive sprouting of dendritic terminals and an
extensive formation of new ribbon synapses within 24 hours. This reactive
synaptogenesis differs strikingly from the primary synaptogenesis and has been
seen thus far only in the inner hair cells. The synaptically engaged neuronal
endings sprout a multitude of filopodia that intussuscept the inner hair cells.
The filopodial tips contain a heavy electron-dense matter that appears to attract
the synaptic ribbons, which form new synaptic contacts with the growing
processes. The intensity of the filopodial growth and synaptogenesis subsides in
about 3 days; the filopodia undergo resorption, leaving behind fibrous
cytoplasmic plaques mostly stored in the supranuclear part of the hair cells.
However, occasional filopodial growth and formation of new synaptic connections
continued. The data demonstrate that any disruption or disturbance of the initial
synaptic contacts between the inner hair cells and their afferent neurons caused
by transplantation results in prompt synaptic reacquisition. Furthermore, we
suggest that the transitory phase of terminal sprouting and multiribbon synapse
formation manifests a trophic dependence that develops postnatally between the
synaptic cells.
PMID- 9658286
TI - Receptor autoradiographic mapping of the mesial motor and premotor cortex of the
macaque monkey.
AB - This study analyzes regional and laminar distribution patterns of
neurotransmitter binding sites in the motor areas of the macaque mesial frontal
cortex. Differences in distribution patterns are compared with the
cytoarchitectonic parcellation. Binding sites were analyzed with quantitative in
vitro receptor autoradiography in unfixed brains of five macaque monkeys. Alpha
amino-3-hydroxy-5-methyl-4-isoxalone propionic acid (AMPA), kainate, and N-methyl
D-aspartate (NMDA) binding sites were labeled with [3H]AMPA, [3H]kainate, and
[3H]MK-801, respectively, muscarinic binding sites with [3H]pirenzepine or
[3H]oxotremorine-M, noradrenergic binding sites with [3H]prazosin or [3H]UK
14304, gamma-aminobutyric acid (GABA)A binding sites with [3H]muscimol, and
serotoninergic binding sites with [3H]ketanserine. Adjacent sections were stained
with a modified Nissl method for cytoarchitectonic analysis. In the motor areas
F1, F3, and F6, [3H]AMPA, [3H]pirenzepine, and [3H]oxotremorine-M binding was
maximal in layers II, III, and V, and [3H]kainate binding was maximal in layers V
and VI. Clear-cut changes in laminar distribution patterns of [3H]AMPA,
[3H]kainate, and [3H]oxotremorine-M binding sites very closely matched
corresponding cytoarchitectonic borders. Mean areal binding densities of all
ligands to F1, F3, and F6 were plotted as polar plots for each area. A polygon
was obtained for each area ("neurochemical fingerprint") when all the density
values belonging to one area were connected with each other. The "neurochemical
fingerprints" of F1, F3, and F6 were virtually identical in shape but increased
in size from F1 to F6. This result reflects the functional similarity of these
motor-related areas and possibly correlates with their differential involvement
in motor control. Areas F1, F3, and F6 can thus be grouped into one
"neurochemical family" of areas.
PMID- 9658287
TI - Distribution of the voltage-dependent calcium channel alpha(1A) subunit
throughout the mature rat brain and its relationship to neurotransmitter
pathways.
AB - The alpha(1) subunit provides both the voltage-sensing mechanism and the ion pore
of voltage-dependent calcium channels. Of the six classes of alpha(1) subunit
cloned to date, alpha)1A) is the subject of debate in terms of its functional
correlate, although it is generally thought to encode voltage-dependent calcium
channels of the omega-agatoxin IVA-sensitive, P/Q type. In the present study, an
alpha(1A)-specific riboprobe and antibody were used with in situ hybridisation
and immunohistochemical techniques to localise alpha(1A) messenger ribonucleic
acid transcripts and subunit protein throughout the mature rat brain. Dual
localisation of alpha(1A) protein and markers for acetylcholine, catecholamines,
and 5-hydroxytryptamine have also been performed in a number of discrete areas.
Abundant and widespread distribution of alpha(1A) protein was found, with
immunoreactivity occurring both in cell bodies and as punctate staining in areas
of neuronal processes. Several associations were noted across alpha(1A)
localisation, defined neuroanatomical regions, and neurotransmitter systems.
However, alpha(1A) expression was not confined to loci corresponding to any one
neurotransmitter type, although a high level of expression was observed in
cholinergic neurones. The distribution of the alpha(1A) subunit in the rat
corresponded well with the limited human mapping data that are available.
PMID- 9658288
TI - Identification of motor neurons to the circular muscle of the guinea pig gastric
corpus.
AB - The projections of enteric neurons to the circular muscle of the guinea pig
gastric corpus were investigated systematically by using the retrogradely
transported fluorescent carbocyanine dye 1,1'-didodecyl-3,3,3',3'-tetramethyl
indocarbocyanine perchlorate (DiI), applied to the muscle layer or myenteric
plexus in vitro. DiI-labeled motor neuron cell bodies were located up to 6.3 mm
aboral, 17 mm oral, and up to 20 mm circumferential to the DiI application site.
Labeled nerve fibers ran for long distances from the DiI application site toward
the greater and lesser curvatures, where they coursed parallel to the bundles of
the "gastric sling" muscle. The majority of labeled cells were located toward the
lesser curvature of the stomach. Nerve cell bodies that were aboral to the DiI
application site were usually small, immunoreactive for choline
acetyltransferase, and, thus, were likely to be excitatory motor neurons. Neurons
that were located orally were larger, fewer in number, and immunoreactive for
nitric oxide synthase and, thus, were likely to be inhibitory motor neurons.
Application of DiI directly to the myenteric plexus filled neurons up to 15 mm
aborally and up to 21 mm orally but labeled few neurons circumferentially. All
nerve cells that were filled from either the circular muscle or the myenteric
plexus had Dogiel type I morphological features. These results demonstrate a
clear polarity of projection of inhibitory and excitatory motor neurons and a
functionally continuous innervation of the circular and gastric sling muscle
layers. Nonmotor neurons in the myenteric plexus were demonstrated, but neurons
with Dogiel type II morphological features are apparently absent.
PMID- 9658289
TI - Choline acetyltransferase expression during a putative developmental waiting
period.
AB - The relationship between the cholinergic expression, morphological development,
and target cell innervation of olivocochlear (OC) efferent neurons was
investigated in the postnatal hamster. Similar to what was found in previous
studies, tracer injections into the contralateral cochlea labeled cells bodies
retrogradely in periolivary regions and labeled cell bodies only rarely in the
lateral superior olive (LSO). Few morphological differences were found among cell
bodies labeled between postnatal day 1 (P1) and P30. Tracer injections into the
crossed OC bundles within the brainstem anterogradely labeled terminals below the
inner hair cells of the cochlea prior to P5 and labeled terminals below outer
hair cells after P5, consistent with a period of transient innervation, as
hypothesized previously. Within the superior olive, choline acetyltransferase
(ChAT) was expressed differentially. In periolivary regions, ChAT was expressed
as early as P0. ChAT-immunoreactive cell bodies in periolivary regions were
similar morphologically to retrogradely labeled OC neurons. In contrast, within
the LSO, ChAT was not expressed until after P2. Consistent with a medical OC
projection to the cochlea at early postnatal ages, ChAT immunoreactivity was
detected below inner hair cells as early as P2 but was not detected below outer
hair cells until after P6. Our results suggest that medial OC neurons not only
provide transient connections to inner hair cells but also may express ChAT when
they are below inner hair cells. Furthermore, these results raise the possibility
that OC neurons may be capable of acetylcholine synthesis and release prior to or
simultaneous with their innervation of the cochlea.
PMID- 9658290
TI - Radiation awareness program for extracorporeal shockwave lithotripsy using
Medstone lithotripters.
AB - To determine the effectiveness of a radiation awareness program in reducing the
radiation exposure to patients treated by a Medstone lithotripter, the exposure
was calculated at the end of each extracorporeal shockwave (SWL) treatment using
a table of measurements of the estimated entrance exposure rates 70 cm from the X
ray tube port. The results, related to stone size and patient weight, were
distributed every month to each radiologic technologist, and a summary was sent
regularly to the treating urologists. The doses before and after the introduction
of the radiation awareness program were compared to determine the effectiveness
of the program, and the chi-square test was used to determine statistical
significance. The average calculated radiation exposure before and after
introduction of the radiation awareness program was 16.39 rad and 8.26 rad,
respectively, for patients with single renal stones; 17.31 rad and 9.02 rad,
respectively, with single ureteral stones; 18.45 rad and 9.39 rad, respectively,
with multiple renal stones; and 20.59 rad and 11.28 rad, respectively with
multiple ureteral stones. These reductions in calculated radiation exposure were
statistically significant only with multiple ureteral stones (P = 0.03). The only
statistically significant differences in the stone-free rates, retreatment rates,
and post-SWL secondary procedure rates before and after the introduction of the
radiation awareness program were seen in the stone-free rates with single renal
stones: 70% v 65%, respectively (P = 0.02); in the retreatment rates with single
ureteral stones: 10% v 6%, respectively ( P < .01); and in the post-SWL secondary
procedure rates with single renal stones: 4% v 2%, respectively (P = 0.01), and
single ureteral stones: 7% v 4%, respectively (P = 0.05). The radiation awareness
program resulted in a 51% reduction in the estimated radiation exposure to
patients during SWL using Medstone lithotripters.
PMID- 9658291
TI - Lipid peroxidation induced by shockwave lithotripsy.
AB - To determine the relation between high-energy shockwaves (HESW) and the presence
of lipid peroxidation produces, juvenile pigs were subjected to shockwave
lithotripsy (SWL). After lithotripsy, both treated and control kidneys were
analyzed, along with urine samples collected before, during, and after SWL.
Thiobarbituric acid-reactive substance (TBARS) and lipid-conjugated diene (CD)
concentrations, used as markers for membrane lipid peroxidation, were determined
in the kidney and urine samples. Significantly increased mean TBARS
concentrations (146%) were associated with homogenates of lithotripsy-treated
kidneys, 77.8 +/- 14.4 (SD) mmol/g v the controls, 31.4 +/- 14.9 mmol/g.
Lithotripsy induction of lipid peroxidation products in the cortex, the gross
damage site, and the respective medulla were also examined. In HESW-treated
cortex samples, increased TBARS concentrations were seen--75.0 +/- 21.3 mmol/g-
compared with untreated controls-- 45.2+/- 5.6 mmol/g--while increased CD
concentrations (168%) were observed in the medulla of HESW-treated samples. No
significant differences were observed in TBARS or CD concentrations in urine
samples from control or treated kidneys, yet specific lipid hydroperperoxides
were detected in the urine of HESW-treated kidneys. We conclude that HESW
lithotripsy of swine kidneys is associated with increased lipid peroxidation
products that may cause further cellular damage. Lipid peroxidation induced by
SWL may be one of several mechanisms that lead to other potential bioeffects.
Finally, analysis of specific lipid hydroperoxides in the urine of HESW-treated
kidneys may serve as a noninvasive marker of renal injury after clinical SWL.
PMID- 9658292
TI - Pneumatic v electrokinetic lithotripsy in treatment of ureteral stones.
AB - Recently, a new device (Combilith) for electrokinetic lithotripsy (EKL) has
become available which is very similar to the well-known device for pneumatic
(ballistic) lithotripsy (Swiss Lithoclast). The Lithoclast uses air pressure to
push a projectile within the handpiece against the end of a metal probe, which is
thereby accelerated and thrown like a jackhammer against the stone. In principle,
the same stroking movement of a small metal probe is provided by EKL; the
difference is that instead of a projectile, a magnetic core within the handpiece
is accelerated by the electromagnetic principle. This paper compares the clinical
efficacy and the features of the two devices. Testing the devices on a stone
model, taking into account stone propulsion, the systems turned out to equally
effective regarding stone disintegration. However, stone displacement was more
pronounced with the Lithoclast applied on easily breaking stones. In a second
experiment, an optoelectronic movement-measuring apparatus (Zimmer camera) was
employed to measure the range and velocity of the movement of the probe tip
without any contact. The linear acceleration velocity ranged from 5 to a maximum
of 12.5 m/sec with both systems, but the maximum height of the stroke was 2.5 mm
with the Lithoclast and 1 mm with EKL. After the initial break-up of soft stones,
further impact of the probe tip against the stone resulted merely in propulsion;
thus, the greater probe stroke height is the cause of the stone displacement. In
a clinical trial, 22 ureteral stones were treated with the Lithoclast and 35 with
the EKL. The two devices were equally effective in terms of stone disintegration
and safety margin. Fixation using a Dormia basket was necessary in 12 cases (8
Lithoclast, 4 EKL). Although a difference in probe stroke height was noted when
comparing pneumatic and electrokinetic lithotripsy, there were no clinically
significant differences in the efficacy of stone fragmentation or stone-free
rates. At the current time, EKL is less costly.
PMID- 9658293
TI - Cost effectiveness of electrohydraulic lithotripsy v Candela pulsed-dye laser in
management of the distal ureteral stone.
AB - To compare the efficacy, safety, and cost of the Candela laser lithotripter with
those of the electrohydraulic (EHL) lithotripter in the management of distal
ureteral stones, 24 patients with obstructing stones were randomized to laser
lithotripsy or EHL. Ureteroscopy was performed with a 6.9F ACMI Miniscope under
general anesthesia. Twelve patients were treated with laser lithotripsy using the
Candela Air-Cooled MDL 2000 LaserTripter System with a 200-micron pulsed-dye
laser fiber. Twelve patients were treated with the Herzog Electrohydraulic
LithoTripter using the 1.9F fiber. The following issues were studied: stone-free
rates, complications (intraoperative, postoperative, and late), and costs of the
procedure. No difference was found in the stone-free or complication rates. One
patient was found to have hydronephrosis at 6 months secondary to an unrelated
proximal ureteral stone. There was no difference in the efficacy of laser
lithotripsy and EHL in the management of distal ureteral stones, but EHL was
found to be significantly more cost effective: the cost for EHL was +336 per
case, whereas, the cost for lasertripsy was +4220 per case, a greater than 10
fold difference.
PMID- 9658294
TI - Holmium laser lithotripsy for ureteral calculi: an outpatient procedure.
AB - A retrospective review was conducted to evaluate the efficacy of ureteroscopic
lithotripsy using the holmium laser with a semirigid endoscope in a newly
established day surgery center. In 1996, 69 consecutive patients (40 male and 29
female) with a mean age of 46.7 (range 21-73) years and ASA status I or II
underwent ureteroscopic lithotripsy for their ureteral calculi using the holmium
laser (365-micron fiber; power setting 0.5-1.4 J/5 Hz) and 8.5F semirigid
ureteroscope in a day surgery setting. Stone features, postoperative pain scores,
readmissions, and complications were evaluated. Eighteen upper, 17 middle, and 34
lower ureteral stones were treated, with a mean size measuring 12.1 (5-45) mm.
The mean operative time was 61 minutes including the anesthetic time (range 15
150 minutes), and the success rate was 91% (63/69). The complication rate was 10%
(7/69) including four unscheduled readmissions (6%). Telephone follow-up on
postoperative Day 1 and Day 3 revealed mean pain scores of 2 and 1, respectively
(on a 0-10 scale) and an analgesic requirement of 1 tablet of Dologesic
(containing 32.5 mg of dextropropoxyphene + 320 mg of paracetamol) four times a
day on both days. Ureteroscopic lithotripsy using the holmium laser and a
semirigid endoscope is highly successful and well tolerated and carries a low
complication rate. It is indicated as an ambulatory and minimally invasive
treatment modality in low-risk patients with ureteral stones.
PMID- 9658295
TI - Stone fragmentation pattern of piezoelectric shockwave lithotripsy in vitro.
AB - Whole stones (N = 64; largest diameter 5-15 mm) were treated in vitro with
piezoelectric shockwaves using the Edap LT-01 lithotripter with 2.5 Hz at either
100% or 54% power. The number of fragments larger than 2 mm was counted after
every 30 seconds. The stones were defined as totally broken when all fragments
were < 2 mm. Total fragmentation time was correlated with the energy level and
the size of the stone. The number of large fragments did not correlate with the
energy level but rather with the original size of the stone.
PMID- 9658296
TI - Percutaneous management of benign adrenal cysts: a treatment option in selected
cases.
PMID- 9658297
TI - Is laparoscopic radical nephrectomy with specimen morcellation acceptable cancer
surgery?
AB - Laparoscopic radical nephrectomy (LRN) for renal-cell carcinoma (RCF) with
removal of the specimen by morcellation and suction remains controversial because
precise pathologic tumor staging is lost, and there is a risk of tumor seeding.
We assessed the theoretical impact of surrendering precise pathologic staging on
the management of patients with low-stage RCC (T3a or less). In 22 patients who
underwent open radical nephrectomy for RCC, the preoperative CT-based clinical
stage was correlated with pathologic tumor staging. Possible clinical inclusion
criteria for LRN were then correlated with pathologic tumor staging. When
comparing clinical and pathologic staging, one patient was understaged and seven
were overstaged by preoperative CT. However, if clinical stage T3a or lower was
used as the inclusion criterion for LRN, 19 patients (86%) would have been so
treated, none would have been underassigned, and future management would not have
been compromised according to pathologic staging. Management of patients with low
stage RCC relying on clinical staging only is oncologically adequate. This would
make LRN an acceptable option for this subset of patients.
PMID- 9658298
TI - Laparoscopic management of ureteral perforation during ureterolithotripsy.
AB - The author presents a case of successful laparoscopic repair of a ureteral
perforation happening during ureterolithotripsy (URS). The perforation of the mid
ureter was managed by a retroperitoneal approach: the stone from the
retroperitoneum was removed, a double-J stent was inserted up to the kidney, the
perforation opening was sutured, and the retroperitoneum was drained. The patient
healed without any complication. Similar management of a ureteral perforation has
not been found in the literature.
PMID- 9658299
TI - Laparoscopic subcapsular nephrectomy.
AB - A 26-year-old patient with end-stage renal disease secondary to vesicoureteral
reflux and recurrent pyelonephritis was referred for bilateral native
nephrectomy. A transperitoneal laparoscopic approach was used. Extremely dense
fibrosis was encountered around the left kidney during the dissection. A left
laparoscopic subcapsular nephrectomy and a right extracapsular nephrectomy were
performed. The indications and surgical technique for laparoscopic subcapsular
nephrectomy are discussed.
PMID- 9658300
TI - Laparoscopic ureteroureterostomy using vascular closure staples in porcine model.
AB - The greatest difficulty in performing a laparoscopic pyeloplasty is the suturing
of the ureteropelvic junction. The purpose of this study was to evaluate the use
of nonperforating titanium vascular closure staple (VCS) clips to perform in
laparoscopic ureteroureterostomy in the porcine model. Six female minipigs
underwent laparoscopic transection of one of the proximal ureters at the level of
the lower pole of the kidney. Ureteroureterostomy was then performed using the
titanium VCS clips. The animals were evaluated at 6 and 12 weeks
postureteroureterostomy with retrograde pyelography and differential creatinine
clearances. At 12 weeks, the animals were euthanized, and the area of
ureteroureterostomy was examined grossly and histopathologically. The technique
for laparoscopic vascular clipping of the ureteroureterostomy proved to be fast
and effective. Follow-up indicated that the method was successful in producing a
functionally patent anastomosis. No encrustation, stone formation, or
intraluminal clip was noted in any of the ureters or kidneys undergoing the
ureteroureterostomy. The area of the ureteroureterostomy showed minimal fibrosis
and inflammation on histopathologic examination. In this animal study, the
nonperforating titanium clips facilitated the performance of a laparoscopic
ureteroureterostomy.
PMID- 9658301
TI - Electromotive drug administration and hydrodistention for the treatment of
interstitial cystitis.
AB - Thirteen patients with interstitial cystitis diagnosed by the NIH criteria were
treated with intravesical electromotive administration of lidocaine and
dexamethasone followed by cystodistention. After a mean follow-up of 10 (range 3
22) months, 8/13 (62%) of the patients reported complete resolution of bladder
symptoms lasting an average 4.5 (range 0.75-17) months. Partial or short-term
improvement of bladder symptoms was observed in three patients, while two
patients reported aggravation of pain for several days after therapy. A
significant increase in bladder capacity, to an average 166% of the pretreatment
capacity, was observed in all patients. Whenever symptoms recurred after
initially effective therapy, retreatments were performed with equal efficacy in
11 patients. This promising new therapeutic approach, performed on an outpatient
basis, may become first-line treatment for patients with interstitial cystitis.
PMID- 9658302
TI - Role of the trigone in micturition.
AB - The exact function of the trigone in the act of micturition is not yet known. The
current communication discusses its role. The myoelectric activity of the urinary
bladder and trigone was studied in nine volunteers (six women, three men; mean
age 38.6 +/- 9.9 years) using Beckman suction electrodes. Two electrodes were
applied to the bladder and one to the trigone. The EMG and vesical pressure were
recorded before and during vesical filling and voiding. Slow waves or pacesetter
potentials (PPs) were recorded at rest from the detrusor and trigone. They had
regular frequency and were followed randomly by bursts of action potentials
(APs). The frequency and amplitude of the trigonal PPs and APs were significantly
lower than those of the vesical tissue. The mean PP frequency was 5.8 +/- 1.8
cycle/min (cpm) and amplitude 0.69 +/- 0.1 mV in the bladder and 3.4 +/- 1.2 cpm
(P < 0.05) and 0.36 +/- 0.09 mV (P < 0.05), respectively, in the trigone. During
vesical filling, neither the vesical pressure nor the vesical and trigonal PPs
and APs registered significant differences from the resting stage (P > 0.05).
During voiding, the vesical electric activity increased and presented as fast
activity spikes or APs of high amplitude (mean 678.6 +/- 88.6 muV). The trigonal
electric activity showed no significant change (P > 0.05) in comparison with the
pre-evacuation status. These findings suggest that the trigone does not contract
during voiding, thus refuting the claim that the trigone is responsible for
preventing ureterovesical reflux on voiding.
PMID- 9658303
TI - Holmium laser resection of the prostate.
AB - A total of 35 patients with benign prostatic hyperplasia (BPH) were treated with
the Ho: YAG laser using a new technique termed holmium laser resection of the
prostate or HoLRP. The laser energy was applied directly to prostatic tissue
exclusively through the use of a standard 550 micron end-firing fiber. A high
powered holmium laser was used and was set at 2.4 J per pulse at 25 pulses per
second for an average power of 60 W. The mean preoperative AUA Symptom Score was
24. Postoperatively, the score dropped to 10.9, 8.2, 5.2, and 4.6 at 1 week, 1
month, 3 months, and 6 months, respectively. The peak urine flow rate improved
from 6.3 mL/sec preoperatively to 15.1, 15.3 and 16 mL/sec at 1 week, 1 month, 3
months, and 6 months. A foley catheter was removed within 24 hours of completion
of the operation in 31 patients (89%), and voiding was improved. The HoLRP
technique was bloodless, and the short-term results were satisfactory. Most
importantly, the defect produced by HoLRP is identical to that of a conventional
transurethral resection. These initial results demonstrate that HoLRP is a useful
surgical alternative in the treatment of patients with obstructive BPH.
PMID- 9658304
TI - Early endoscopic realignment as primary therapy for complete posterior urethral
disruptions.
AB - We assessed the outcome of early endoscopic realignment of posterior urethral
disruptions. We evaluated six patients who underwent early or delayed endoscopic
realignment for the disrupted posterior urethra over a 3-year period. C-Arm
fluoroscopy guidance and orientation in two planes were used as necessary.
Potency, restructure rates, and continence were assessed in addition to hospital
length of stay, intraoperative blood loss, and uroflow. The collective results of
ten publications were also reviewed. In the present study, all of the six
patients were continent. One had diminished erectile capability, and four
required subsequent internal urethrotomies. Evaluation of the cumulative data
(including the present study) showed an overall 9% incontinence rate, 60% potency
rate, and 54% restricture rate. Endoscopic realignment of the disrupted posterior
urethra is a minimally invasive procedure with results comparable to those of
open delayed urethroplasty. Early and delayed repairs have been applied with
similar results, the former being advocated in patients who are medically and
orthopedically stable. Hospital stay, loss of work, morbidity, and related
complications are also markedly decreased with early endoscopic realignment.
PMID- 9658305
TI - Influence of decay of laser fibers during laser prostatectomy on clinical
results.
AB - Three types of sidefiring laser fibers (34 Urolase, 20 Ultraline, and 114 Prolase
II) were visually inspected after a laser prostatectomy, and transmission
measurements were performed using a power meter (Aquarius). The results were
correlated with the clinical outcome. Despite differences in the amount of loss
in transmission for the fibers used, we could not establish any significant
effect on clinical outcome measures, such as improvement in maximal flow rate or
symptom score. The visual aspect of the Urolase fibers was significantly related
to the amount of transmission loss, whereas no such relation was found for the
other two types of fibers. Prostate size and the total amount of energy delivered
by the laser source also did not correlate with the clinical outcome. To
determine the relation between the energy absorbed by the prostate and clinical
outcome, a large number of patients must be evaluated, and any factor that can be
controlled needs to be monitored. For the latter, the power meter as presented
here is a useful complementary tool.
PMID- 9658306
TI - Effects of transjugular intrahepatic portosystemic shunt (TIPS) on esophageal
motor function and gastroesophageal reflux.
AB - The effects of transjugular intrahepatic portosystemic shunt (TIPS) placement on
esophageal motor function and gastroesophageal reflux were investigated in
patients with esophageal varices. In six men with esophageal varices, esophageal
manometry and upper gastrointestinal endoscopy were performed before and 15-20
days after TIPS placement. Intraesophageal pH monitoring was performed in the
four patients with severe esophageal varices (defined as the largest sized
varices) following TIPS placement. Findings were compared with those in six
healthy men (controls) who underwent esophageal manometry and intraesophageal pH
monitoring. The esophageal varices resolved or were reduced after TIPS placement.
Resting lower esophageal sphincter (LES) pressures were similar in the study
group before and after TIPS placement and in the control subjects. The incidence
and progression of esophageal contractions were similar in the study group before
and after TIPS placement and in the control subjects. At 3 cm above the LES, the
amplitude of esophageal contraction after TIPS placement was significantly higher
than that before TIPS placement. At 3 and 8 cm above the LES, the amplitude of
esophageal contraction in the control subjects was significantly higher than that
in the study group before and after TIPS placement. Esophageal acid exposure time
after TIPS placement was similar to that in the controls. TIPS placement is a
useful treatment that improves esophageal motor function without the occurrence
of pathologic gastroesophageal reflux.
PMID- 9658307
TI - Electrogastrographic power ratio in humans is not related to changes in antrum
skin distance but to antral motility.
AB - It is not clear whether the power increase in electrogastrography (EGG) after
meal or water ingestion reflects increases in gastric motility or gastric
distension bringing the stomach closer to the electrodes on the abdominal skin
surface. We recorded EGG and real-time ultrasonography simultaneously before and
after 150-ml water ingestion in 17 healthy volunteers. We calculated gastric
power, by spectral analysis of EGG by the maximum entropy method, for 400 s
before and after water ingestion, and calculated their ratio (power ratio). We
calculated, using sonography, the number of antral contractions before and after
water ingestion, the motility index after water ingestion, the distance between
the antrum and the abdominal skin surface before and after water ingestion, and
the ratio of these distances (distance ratio). The number of contractions was
positively correlated with gastric power before water ingestion, and the antrum
skin distance was negatively correlated with gastric power both before and after
water ingestion. The motility index after water ingestion was positively
correlated with both gastric power after water ingestion (Spearman's rank
correlation r = 0.492; P = 0.0498) and the power ratio (r = 0.615; P = 0.0141).
There was no correlation between the distance ratio and the power ratio. These
results suggest that the power increase in EGG induced by water ingestion does
not reflect the approach of the antrum to the abdominal surface, but rather,
reflects antral motility after water ingestion.
PMID- 9658308
TI - Hydrogen peroxide-induced cellular injury is associated with increase in
endogenous fluorescence from rat gastric mucosal epithelial cell culture: A new
method for detecting oxidative cellular injury by fluorescence measurement.
AB - To develop a new method of detecting cellular injury caused by oxygen radicals,
we studied endogenous fluorescence from the cultured cells of a rat gastric
mucosal epithelial cell line. Measurement with an ultra-high sensitivity camera
image processor system under an inverted epifluorescence microscope showed that
the fluorescence intensity of the cells increased time- and dose-dependently
after the addition of hydrogen peroxide (H2O2), an oxygen radical precursor, to
the medium. This increase was inhibited by the presence of catalase. Phase
contrast and fluorescence microscopy revealed that the fluorescence was emitted
from granular substances in the cytoplasm of the injured cells. The spectral
pattern of excitation and emission indicated that the fluorescent substances were
flavins. In cell-free experiments, glutathione reductase which has flavin adenine
dinucleotide (FAD) at the active site, increased in fluorescence after incubation
with H2O2 in the presence of reduced glutathione and glutathione peroxidase.
These findings indicate that FAD in the cytoplasm of cells injured by H2O2
increased in endogenous fluorescence according to the extent of injury, and
suggest that fluorescence measurement may be a simple method in cellular
toxicology to detect oxygen radical-induced injuries.
PMID- 9658309
TI - Type IIa early gastric cancer with proliferation of xanthoma cells.
AB - We report a type IIa early gastric cancer associated with xanthoma cell
proliferation in a 61-year-old man. The patient was admitted to our hospital
because of a gastric polyp detected at a medical checkup. An irregular protruding
lesion with xanthoma cell proliferation was detected endoscopically. Histological
examination showed a well differentiated tubular adenocarcinoma in the mucosa
associated with xanthoma cell proliferation. The distribution of the xanthoma
cells in the stroma corresponded closely with that of the cancer cells. Neither
atypism nor mitotic figures were recognized in the xanthoma cells. In an
immunohistochemical study, almost all the xanthoma cells were stained positive
for alpha 1-antitrypsin, while relatively few exhibited positive S-100 protein
staining. Specific monocyte chemotactic and activating factor immunoreactivity
was present only in the xanthoma cells, and not in the cancer cells. On the basis
of these findings, it was speculated that the gastric cancer cells may have
caused the xanthoma cell proliferation via an autocrine mechanism i.e., by a
chemical mediator acting in a paracrine or juxtacrine manner.
PMID- 9658310
TI - Quantification of Helicobacter pylori infection: Simple and rapid 13C-urea breath
test in Taiwan.
AB - The 13C-urea breath test (13C-UBT) is a non-invasive method for detecting
Helicobacter pylori. This study was performed to determine the cutoff value and
evaluate the sensitivity and specificity of 13C-UBT in Taiwan. 13C-Urea (100 mg
of 99% 13C-labeled urea) was dissolved in 50 ml sterile water for the test. The
test meal for delaying gastric emptying was 100 ml fresh milk. Patients fasted
for at least 6h. A baseline breath sample was collected 5 min after they had the
test meal. Two other samples were collected at 15 and 30 min after the patients
ingested the 13C-urea. The test was evaluated in 352 patients after routine upper
gastrointestinal endoscopy, and the urease test, culture, and histopathology were
taken as the gold standards for detecting H. pylori. According to the receiver
operating characteristic (ROC) curves, we chose values of 2.8 and 4.2 excess
delta 13CO2 per mil as the cut-off values for 15 and 30 min, respectively, post
13C-urea. The sensitivity and specificity of 13C-UBT were 99% and 93% at 15 min,
and 98% and 93% at 30 min post 13C-urea, respectively. The 13C-UBT breath test is
an efficient non-invasive method of high sensitivity and high specificity for
detecting H. pylori infection. We suggest that the use of fresh milk as the test
meal and the detection of excess delta 13CO2 15 min after the ingestion of 13C
urea are suitable for the clinical use of 13C-UBT. This test is simple and rapid.
PMID- 9658311
TI - Endoscopic findings in transplanted allo-intestine of rats after discontinuance
of immunosuppressive agent.
AB - In clinical practice, graft rejection in small-bowel transplantation should be
diagnosed before irreversible condition of the graft. We have already reported
the usefulness of endoscopic examination for the early detection of acute
rejection in a rat model. Here we evaluated rejection after discontinuance of
methyl-deoxyspergualin by endoscopy. Heterotopic small-bowel transplantation was
performed by the cuff method from a DA to a LEW rat. Endoscopic and histological
examinations were performed through the stomas. Two-week administration of methyl
deoxyspergualin significantly prolonged graft survival. Graft rejection after
discontinuance of the agent occurred much more slowly than rejection without the
immunosuppressive drug. Erosive mucosal changes were endoscopically observed in
the early phase of rejection in rats that did not receive the immunosuppressant.
However, endoscopic findings after discontinuance of methyl-deoxyspergualin
indicated edematous changes and thickening of the wall without erosion, and,
histologically, the grafted intestine showed slowly-progressing rejection with
flattened villi. If we pay attention to edematous changes and hardening of
intestinal wall, and take selective biopsies, endoscopic examination may improve
the early diagnosis of slowly progressive rejection in the clinical setting.
PMID- 9658312
TI - Telomere shortening in the colonic mucosa of patients with ulcerative colitis.
AB - Telomere length in human somatic cells gradually decreases with the number of
cell divisions and is regarded as a marker of somatic cell turnover. Mucosal
cells of the affected colon show rapid turnover in individuals with active
ulcerative colitis (UC). Telomere length was determined by Southern blot analysis
of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients
with UC in remission, two of whom showed dysplasia, and 17 control subjects
without colitis. For each individual, mean TRF length was compared between rectal
mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was
significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb
versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no
significant difference was detected in the control subjects. The extent of
telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/-
0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients,
two of whom had dysplasia, showed telomere shortening of more than 20% in the
rectal mucosa. These observations suggest that telomere shortening in the colonic
mucosa of individuals with UC may represent the history of mucosal inflammation
during disease of long duration, and that it may contribute to aneuploidy in UC.
PMID- 9658313
TI - Clinical significance of serum levels of CD44 variant exons 8-10 protein in
colorectal cancer.
AB - We examined serum levels of a CD44 splice variant that contained variant exons 8
10 (CD44v8-10) as a tumor marker in colorectal cancer patients. We performed
enzyme-linked immunosorbent assays in 81 sera obtained from 71 colorectal cancer
patients and 10 healthy controls. Serum CD44v8-10 levels were significantly
higher in the colorectal cancer patients than in the healthy controls (0.209 +/-
0.098 versus 0.114 +/- 0.019 OD; P < 0.01). There was a close correlation between
immunohistochemical expression and serum CD44v8-10 levels. Surgical resection of
the tumors resulted in a reduction of serum CD44v8-10 levels. There was no
significant correlation between serum CD44v8-10 level and serosal invasion or
histologic type. However, a significant correlation was observed between serum
CD44v8-10 level and lymphatic or venous invasion. In addition, serum CD44v8-10
levels were significantly higher in carcinomas associated with lymph node or
liver metastasis than in those without metastasis. These findings suggest the
usefulness of serum CD44v8-10 level in the prediction of colorectal cancer
metastasis.
PMID- 9658314
TI - Detection of circulating anti-MUC1 mucin core protein antibodies in patients with
colorectal cancer.
AB - MUC1 mucin has a unique immunogenic peptide epitope in the extracellular domain,
which has been shown to induce humoral and cellular immune response. In this
study, we evaluated the pathophysiological significance of circulating anti-MUC1
mucin core protein IgG antibodies (anti-MUC1 antibodies) in colorectal cancer by
Western blot analysis and 51Cr release assay. Anti-MUC1 antibodies were detected
in 5 of 31 (16.1%) healthy subjects and in 27 of 56 (48.2%) patients with
colorectal cancer. The presence of circulating anti-MUC1 antibodies was not
significantly correlated with the level of circulating antigen MUSE11 or with
other clinicopathological parameters tested. The incidence of positivity for anti
MUC1 antibodies in stage I and II (staged according to the General Rules for
Clinical and Pathological Studies on Cancer of the Colon and Rectum of the
Japanese Research Society for Cancer of the Colon and Rectum) cancers was 45.5%
and 58.8%, respectively, suggesting that positivity for these antibodies may be
of use as an adjunct for the diagnosis of colorectal cancer in the early stages
in the absence of serious complications such as liver diseases. Because of the
epitope similarity, anti-MUC1 antibodies in the serum may function in a manner
similar to that of anti-MUC1 peptide monoclonal antibodies (mAbs). We therefore
observed antibody-dependent cell mediated cytotoxicity with anti-MUC1 peptide mAb
using MUC1 cDNA-transfected colon cancer CHC-Y1 cells as the target. The
decreased sensitivity of MUC1 transfectants to effector cells was restored to a
level equivalent to that in control cells. These data suggest that the detection
of circulating anti-MUC1 antibodies may be a useful adjunct for the early
diagnosis and immunological analysis of colorectal cancer.
PMID- 9658315
TI - Altered hepatic hemodynamics and improved liver function following intrahepatic
vascular infusion of prostaglandin E1.
AB - Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1
influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we
carried out an experimental and a clinical study. PGE1 was continuously
administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of
0.01 micrograms/kg per min in healthy mongrel dogs. In the clinical study, in
eight patients PGE1 was administered through the hepatic artery at a rate of 0.01
micrograms/kg per min after hepatic lobectomy. In the experimental study, hepatic
hemodynamics and oxygen metabolism did not change during the administration of
PGE1 into the portal vein. During administration of PGE1 into the hepatic artery,
hepatic arterial flow increased 1.5-fold after administration compared to the
rate before administration (P < 0.01). Hepatic arterial pressure, hepatic
arterial resistance, and post-sinusoidal resistance significantly decreased after
administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen
supply increased significantly (P < 0.01). In the patients, serum glutamic
oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels
remained low after surgery, and the recovery of protein synthesis was improved
compared with that in eight hepatectomized patients without PGE1 administration
(controls). The intrahepatic arterial infusion of PGE1 was considered useful for
the recovery of liver function.
PMID- 9658316
TI - Reduced expression and rare genomic alteration of nm23-H1 in human hepatocellular
carcinoma and hepatoma cell lines.
AB - We investigated the expression and genomic alteration of nm23-H1 (which encodes a
nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs)
and four hepatoma cell lines. The expression of nm23-H1 protein was significantly
reduced in HCCs with intrahepatic metastasis (72%) compared with expression in
HCCs without intrahepatic metastasis (38%). However, in two of three HCCs
examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was
not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated
carcinoma) revealed marked reduction of nm23-H1 protein compared with two other
hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the
three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12
HCCs examined. No point mutation in the coding region of the nm23-H1 gene was
observed in any of the 12 HCCs or the four hepatoma cell lines. These findings
suggest that: (i) the expression of nm23-H1 protein is inversely associated with
high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may
occasionally occur at both the transcriptional and post-transcriptional levels in
HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.
PMID- 9658317
TI - Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker
for metastasis in human hepatocellular carcinoma.
AB - Vascular endothelial growth factor (VEGF) is closely related to angiogenesis in
various human cancers. However, little is known of its circulating levels in
hepatocellular carcinoma (HCC). We examined circulating VEGF levels in chronic
liver disease to assess their clinical significance. Plasma VEGF concentrations
were determined, by enzyme immunoassay, in patients with chronic hepatitis (CH; n
= 36), liver cirrhosis (LC; n = 77), and HCC (n = 86) for a cross-sectional
study. Plasma VEGF levels in healthy controls (n = 20) and CH, LC, and HCC
patients were 17.7 +/- 5.4 (mean +/- SD), 30.6 +/- 22.8, 34.4 +/- 27.0, and 51.1
+/- 71.9 pg/ml, respectively. The levels were significantly elevated in the HCC
group, compared with the control, CH, and LC groups. Plasma VEGF levels in stage
I, II, III, IVA, and IVB HCC patients were 27.6 +/- 16.1, 26.5 +/- 13.7, 35.8 +/-
15.3, 45.4 +/- 39.4, and 103.1 +/- 123.2 pg/ml, respectively. The stage IVB
patients with remote metastasis showed significantly marked elevation compared
with the patients at the other stages. Platelet numbers were weakly correlated
with plasma VEGF levels in the HCC group. Plasma VEGF level was highly elevated
in patients with HCC, particularly those with metastatic disease. We consider
that plasma VEGF is a possible tumor marker for metastasis of HCC. Circulating
VEGF may be derived mainly from the large burden of tumor cells, and partly from
platelets activated by the vascular invasion of HCC cells.
PMID- 9658318
TI - TGF-beta isoforms in alcoholic liver disease.
AB - The increased deposition of extracellular matrix proteins in the liver is a key
factor in the morbidity and mortality of alcoholic liver disease (ALD). This
increased fibrosis may be due to a superabundance of profibrogenic factors such
as transforming growth factor-beta (TGF-beta). The original peptide is now called
TGF-beta 1, and two other isoforms have been recognized in humans (TGF-beta 2 and
TGF-beta 3). It was the aim of the present study to determine the expression of
the TGF-beta isoforms in different stages of ALD. Thirty patients with ALD had
percutaneous liver biopsies performed for diagnostic purposes. They were grouped
by clinical findings and by liver histology into four groups: I, steatosis; II,
fibrosis; III, hepatitis; and IV, cirrhosis. An unused portion of each biopsy
sample was used to evaluate the gene expression of TGF-beta 1, TGF-beta 2, and
TGF-beta 3 by reverse transcription polymerase chain reaction (RT-PCR). The
expression of all isoforms from patients was significantly greater than their
expression in controls. No significant correlation was determined between TGF
beta isoform expression and liver function test results. When the different
isoforms were grouped by histology, increased expression with more severe disease
was found; however, differences existed among the isoforms. In ALD, all TGF-beta
isoforms were increased and their expression was significantly greater in
patients with more active and advanced disease. RT-PCR is an effective method for
evaluating gene expression in clinical samples which often provide a limited
amount of tissue.
PMID- 9658319
TI - Detection of Ki-ras and p53 gene mutations in tissue and pancreatic juice from
pancreatic adenocarcinomas.
AB - Pancreatic carcinomas have a high incidence of Ki-ras mutations, and the genetic
change is thought to occur at an early stage in the carcinogenesis. The aim of
this study was to evaluate the usefulness of detecting genetic mutations in pure
pancreatic juice (PPJ). DNA was extracted from tissue specimens of pancreatic
carcinomas and from cells in PPJ, and subjected to polymerase chain reaction
single-strand conformation polymorphism analysis. Two types of mobility shifts
that indicate Ki-ras mutations were observed in 13 of the 20 (65%) tissue
specimens obtained by operation or autopsy. Ten of 15 specimens (67%) of PPJ
collected from patients with pancreatic carcinomas showed two types of mobility
shifts. Conventional imaging techniques did not show two in 10 of these patients.
PPJ from patients with non-cancerous pancreatic diseases showed no Ki-ras
mutations. The p53 tumor suppressor gene, examined by PCR-SSCP analysis, was
mutated in 8 of the 20 tissue specimens obtained by operation or autopsy (40%).
The detection of Ki-ras and p53 mutations in PPJ could be useful for the early
diagnosis of pancreatic carcinomas, especially for neoplastic lesions of the
intraductal type.
PMID- 9658320
TI - Primary cancer of the small intestine and mutational analysis of the K-ras and
p53 genes.
AB - A 69-year-old woman was admitted to Hokuso Shiroi Hospital because of recurrent
pain in the lower right side of the abdomen. Small-intestinal cancer was strongly
suspected after fluoroscopy of the small intestine. Laparotomy showed advanced
cancer of the ileum, of complete annular constrictive type, 9.5 x 5cm in size.
Histologically it was moderately differentiated tubular adenocarcinoma. Neither
visceral nor nodal metastases were found, and the patient has been well for the
20 months since surgery. The strong resemblance between the epidemiological
characteristics of small-intestinal cancers and colorectal cancers prompted us to
investigate the carcinogenetic mechanisms at the molecular level. A point
mutation at codon 12 of the K-ras gene was found, while no alterations were noted
in the p53 gene, whose mutations are frequent in colon cancers. The
carcinogenetic mechanisms of the small-intestinal cancer we experienced may thus
differ from those of colon cancers.
PMID- 9658321
TI - Anorectal leiomyosarcomas.
AB - In adults, rectal leiomyosarcoma is uncommon, and anal leiomyosarcoma is even
more rare. We report one patient with anal leiomyosarcoma and one patient with a
biphasic clinical history, with three occurrences of perineal leiomyosarcomas
after surgically resected rectal leiomyoma. We discuss the characteristics of
these rare entities based upon a review of the literature.
PMID- 9658322
TI - Pyoderma gangrenosum complicating ulcerative colitis: Successful treatment with
methylprednisolone pulse therapy and cyclosporine.
AB - A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma
gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative
colitis had been well controlled with oral prednisolone, but ulcerative colitis
relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The
pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but
relapsed when prednisolone was tapered. A second trial of pulse therapy combined
with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and
no recurrence was recognized after prednisolone was tapered. This is a very rare
case of successful treatment with methylprednisolone pulse therapy combined with
cyclosporine for pyoderma gangrenosum complicating ulcerative colitis.
PMID- 9658323
TI - Fulminant hepatitis complicated by small intestine infection and massive
hemorrhage.
AB - A 34-year-old man diagnosed with fulminant hepatitis, caused by hepatitis B
virus, and acute renal failure was referred to our hospital. After admission to
the intensive care unit, the liver and renal failure were ameliorated. Melena
requiring transfusion occurred during the course of his illness. Endoscopic
examination demonstrated pseudomembranes, erosions, ulcers, and hemorrhage in the
duodenum, the upper jejunum, and the terminal ileum, suggesting widespread
lesions throughout the small intestine. Pseudomonas putida, Xanthomonas
maltophilia, and Candida glabrata were cultured from ileal fluid. Candida
glabrata was also detected in sputum, feces, and on an intravenous catheter tip.
The patient was treated with amphotericin B and miconazole. The melena was
ameliorated, but inflammation of the small intestine persisted. Although we had
difficulty in treating the enteritis, the patient survived, and 1 year later
colonoscopic examination demonstrated no abnormalities. The small intestine is a
difficult site to examine, but endoscopic examination of this site is important
when massive hemorrhage develops.
PMID- 9658324
TI - Two patients with acute hepatitis B with suspected sexual transmission of
hepatitis G virus.
AB - Two patients with acute hepatitis B with suggested sexual transmission of
hepatitis G virus (HGV) are reported. A total of 18 patients with community
acquired acute hepatitis B were analyzed in this study. Two of the 18 patients
(patients 1 and 2) were positive for serum HGV RNA at the initial consultation.
Both patients had had sexual contact with prostitutes several weeks before the
onset of acute hepatitis, and hepatitis B virus (HBV) was suggested to be
infected through the sexual contacts. These patients showed no other history of
exposure to possible transmission routes for blood-borne hepatitis viruses.
Patient 1 was diagnosed as with acute HGV infection because the antibody to HGV
envelope-2 protein seroconverted to positive during the course of acute
hepatitis. HGV RNA was negative in a serum sample collected from patient 2 before
the onset of acute hepatitis, also suggesting acute HGV infection. These results
indicate that in patients 1 and 2 HGV was infected along with HBV through sexual
contact. The clinical manifestations of acute hepatitis in the two patients with
HGV co-infection did not differ from those in the 16 patients with HBV infection
alone.
PMID- 9658325
TI - Use of balloon-occluded retrograde transvenous obliteration with ethanolamine
oleate for the treatment of hepatic encephalopathy in a cirrhotic patient with a
large spontaneous splenorenal shunt.
AB - We describe a technique for the treatment of hepatic encephalopathy in a
cirrhotic patient with a large spontaneous splenorenal shunt. This large shunt
was successfully occluded without severe complications by retrograde transrenal
venous obliteration with ethanolamine oleate after balloon occlusion. This
procedure may be an effective method to occlude a large spontaneous splenorenal
shunt for the treatment of hepatic encephalopathy.
PMID- 9658326
TI - An autopsy case of granulocytic sarcoma of the porta hepatis causing obstructive
jaundice.
AB - We describe an extremely rare case of granulocytic sarcoma of the porta hepatis
causing obstructive jaundice. The patient was an 84-year-old man admitted because
of obstructive jaundice. Ultrasonography (US) and computed tomography (CT)
scanning of the abdomen disclosed a mass about 2.5 cm in diameter near the neck
of the gallbladder, and thickening of the gallbladder wall. Based on these
findings, gallbladder carcinoma was suspected. After endoscopic retrograde
biliary drainage (ERBD) was performed, the jaundice resolved. However, blast
cells were detected in the peripheral blood 51 days after admission, and
laboratory studies disclosed acute myelocytic leukemia (AML: French-American
British [FAB] type M0). We treated him conservatively, with antibiotics and ERBD
but he died of disseminated intravascular coagulation. Autopsy showed that the
suspected gallbladder carcinoma was actually a granulocytic sarcoma arising in
association with AML and causing obstructive jaundice. The largest tumor involved
the porta hepatis. It should be kept in mind that granuloctyic sarcoma is a
possible cause of obstructive jaundice, even in patients with no evidence of AML.
PMID- 9658327
TI - Pancreaticoduodenal artery aneurysms associated with celiac axis stenosis due to
compression by median arcuate ligament and celiac plexus.
AB - Celiac axis stenosis is frequently associated with pancreaticoduodenal artery
aneurysms. Although the cause of stenosis was not clear in most of the reported
cases, compression of the median arcuate ligament of the diaphragm was found to
be responsible for the stenosis in 7 of 42 reported cases of this type of
aneurysm. We report a case of aneurysm caused by compression of the median
arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old
Japanese man was admitted with a low echoic lesion in the uncus of pancreas.
Computed tomographic scan and angiogram revealed stenosis of the celiac axis and
two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac
plexus and median arcuate ligament were divided surgically and normal flow was
reestablished in the celiac axis. One of the aneurysms was resected and the
afferent artery of the other aneurysm was ligated. In the setting of
pancreaticoduodenal artery aneurysm associated with celiac axis stenosis,
management of stenosis should be considered in addition to local treatment of the
aneurysm. In this context, division of median arcuate ligament and celiac plexus
or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade
and could be effective in preventing aneurysm reformation.
PMID- 9658328
TI - Two synchronous solid and cystic tumors of the pancreas.
AB - We report a 17-year-old woman who had two synchronous solid and cystic tumors of
the pancreas (SCTP) detected by abdominal echography and computed tomography.
There was a 6 x 5 cm mass in the pancreatic body and a 3 x 3 cm mass in the tail,
with the two lesions being separate. No distal metastases were detected. The
resected tumors consisted of solid and cystic components and both were well
demarcated with fibrous capsules. The larger tumor was predominantly solid and
the smaller one was mostly hemorrhagic. On microscopy, the tumor cells were
small, eosinophilic, and arranged, in part, like pseudorosettes. The tumor cells
were immunohistochemically positive for alpha-1 antitrypsin, neuron-specific
enolase, and synaptophysin. The final diagnosis was SCTP arising synchronously
and independently at two sites. As far as we know, only one case of multicentric
SCTP has been reported previously. Local recurrence of SCTP suggests the
possibility of multicentric occurrence, and we believe that reports of such cases
may increase in the future with advances in echography and computed tomography.
PMID- 9658329
TI - Pancreatic pseudocyst associated with eating disorder.
AB - We describe a patient with an eating disorder and hyperamylasemia originating
from the salivary glands, who developed pancreatitis with a huge pancreatic
pseudocyst. A 40-year-old woman was referred for the treatment of an eating
disorder that had persisted for 9 years. She was admitted with abdominal pain,
diarrhea, and nausea. She had bilateral parotid enlargement with marked elevation
of total serum amylase level (3288 IU/l; normal range, 60-220) and an isolated
increase of salivary isoamylase activity. After her symptoms resolved, oral
intake of food was commenced. She subsequently complained of abdominal pain; this
was associated with a slight elevation of serum pancreatic isoamylase and lipase
levels, and a huge pancreatic pseudocyst was detected. Percutaneous drainage of
the pseudocyst was successful. Endoscopic retrograde cholangiopancreatography
demonstrated irregularity of the pancreatic duct. Based on these findings, the
final diagnosis was parotid enlargement and acute exacerbation of chronic
pancreatitis associated with a pancreatic pseudocyst in a patient with an eating
disorder.
PMID- 9658330
TI - Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.
AB - CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large
intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of
CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9
ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA;
normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high
in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of
CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in
diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were
higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP)
and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were
elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or =
10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three
times during the clinical course in 2 CC patients and in 6 HCC patients, and
increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC
patients. Marked increases in serum CYFRA 21-1 levels in patients with large
liver cancers, particularly in those with normal levels of AFP and PIVKA II,
would suggest the existence of intrahepatic CC rather than HCC.
PMID- 9658331
TI - Multiple early bile duct carcinoma associated with congenital choledochal cyst.
AB - Emergency ultrasonography showed a protruding tumor in the markedly dilated
common bile duct of a 33-year-old Japanese woman. Magnetic resonance
cholangiopancreatography also demonstrated the tumor clearly, almost as clearly
as did percutaneous transhepatic cholangiography. With a diagnosis of common bile
duct carcinoma associated with congenital choledochal cyst,
pancreaticoduodenectomy was performed. In the resected specimen, as well as the
protruding tumor, there was also a small slightly elevated lesion. Pathology
examination showed adenocarcinoma limited to the fibromuscular layer in the
protruding tumor, and adenocarcinoma limited to the mucosa in the elevated
lesion. Prophylactic total excision of the choledochal cyst before the occurrence
of malignant change is strongly recommended in patients with congenital
choledochal cyst. However, in those who are reluctant to undergo the operation,
periodic follow-up with ultrasonography and magnetic resonance
cholangiopancreatography would be ideal to achieve early detection of malignant
change.
PMID- 9658332
TI - Ulcerative colitis and Crohn's disease--susceptibility genes and clinical
patterns.
PMID- 9658333
TI - GB virus C/hepatitis G virus infection in autoimmune liver diseases.
PMID- 9658335
TI - A neurite outgrowth-inhibitory proteoglycan expressed during development is
similar to that isolated from adult brain after isomorphic injury.
AB - The expression of proteoglycans (PGs) in the mammalian central nervous system
(CNS) appears to be strictly regulated both during development and after damage
to the mammalian CNS. Recently, we have isolated from membranes of injured adult
brain a neurite outgrowth-inhibitory proteoglycan (IMP), the activity of which
could be specifically counteracted by a monoclonal antibody (mAB) against the PG.
We described in this report the characterization of perinatal membrane
proteoglycan (PMP), a heparan-sulfate/chondroitin-sulfate-containing PG expressed
during brain development. Its maximal expression was observed around postnatal
day 3, decreasing strongly in normal adult tissue. This PG was purified and
characterized using mABs generated against IMP. The comparison of PMP and IMP
properties indicates that the two PGs are highly related and share expression
patterns, biochemical characteristics, and the ability to inhibit neurite
initiation in culture. However, IMP and PMP displayed a distinct effect on
neurite elongation, which may be explained by their differences in glycosilation
pattern. The data presented in this report support the idea that proteoglycans
expressed during CNS development are re-expressed following injury.
PMID- 9658334
TI - Insulin-like growth factor-1 is a radial cell-associated neurotrophin that
promotes neuronal recruitment from the adult songbird edpendyma/subependyma.
AB - In the adult songbird forebrain, neurons continue to be produced from precursor
cells in the forebrain ependymal/subependymal zone (SZ), from which they migrate
upon radial guide fibers. The new neurons and their radial cell partners may
coderive from a common SZ progenitor, which may be the radial cell itself. On
this basis, we asked whether radial cells might provide trophic support for the
migration or survival of newly generated neurons. We focused upon the insulin
like growth factors (IGFs) IGF-1 and IGF-2, which have previously been shown to
support the survival and differentiation of neural progenitor cells. We found
that IGF-1 immunoreactivity was expressed heavily by adult zebra finch radial
cells and their fibers, with little expression otherwise. IGF-2, in contrast, was
expressed by parenchymal astrocytes and exhibited little radial cell expression.
Despite their distinct distributions, IGF-1 and IGF-2 exerted similar trophic
effects on finch SZ cells in vitro; both greatly increased the number of neurons
migrating from explants of the adult finch SZ, relative to explants raised in low
insulin, IGF-1-deficient media. However, neither factor extended neuronal
survival. These results suggest that in neurogenic regions of the adult avian
forebrain, IGF-1 acts as a radial cell-associated neuronal differentiation and/or
departure factor, which may serve to regulate neuronal recruitment into the adult
brain.
PMID- 9658336
TI - Regulation of aromatase, 5 alpha- and 5 beta-reductase in primary cell cultures
of developing zebra finch telencephalon.
AB - Sex steroids act on the developing and adult telencephalon of songbirds to
organize and activate the neural circuits required for the learning and
production of song. Presumably, the availability of active androgens and
estrogens to steroid-sensitive neural circuits controlling song is modulated by
the local expression of androgen-metabolizing enzymes. Two enzymes, 5 alpha- and
5 beta-reductase, are expressed widely in the songbird telencephalon, as they are
in the telencephalons of other avian species. These enzymes convert circulating
testosterone (T) into the active and inactive metabolites, 5 alpha- and 5 beta
dihydrotestosterone (DHT), respectively. A third enzyme, aromatase, converts T
into estradiol (E2) and is expressed at unusually high levels in several regions
of the songbird telencephalon. In many tissues, including the brain, the
regulation of expression of one or more of these enzymes can be a critical
feature of their ability to control the production of active sex steroids. We
have used primary cell cultures to examine factors that might regulate the
expression of these enzymes in developing zebra finch telencephalon. Cultures
were treated for 0-72 h with sex steroids (T, E2, 5 alpha-DHT, and 5 beta-DHT) or
with dibutyryl cAMP. Afterward, activities of aromatase, 5 alpha- and 5 beta
reductase were determined or total RNA was extracted for Northern analysis.
Treatments with cAMP increased both aromatase activity and aromatase mRNA levels
by 220%. E2 significantly reduced aromatase activity by an average 65%, whereas 5
alpha- and 5 beta-DHT had no effect on aromatase activity. Compared to untreated
controls, E2 treatment decreased aromatase mRNA levels by 56%. None of these
treatments consistently affected either 5 alpha- and 5 beta-reductase activities.
These results suggest that telencephalic E2 may regulate its own synthesis by
repression of aromatase expression, whereas factors that upregulate cAMP in the
telencephalon can increase the local concentrations of E2.
PMID- 9658337
TI - Glomerulus development in the absence of a set of mitral-like neurons in the
insect olfactory lobe.
AB - Mitral cells are the first neurons in the mammalian olfactory bulb to synapse
with olfactory receptor axons during glomerulus development, and in an
invertebrate, the moth Manduca sexta, mitral-like neurons overlap very early with
olfactory receptor axons as they begin to form protoglomeruli. The possibility
for early interaction between receptor neurons and mitral-like neurons led us to
ask whether such an interaction plays an essential role in glomerulus
development. In the current study in the moth, we surgically removed a major
class of these mitral-like neurons before glomeruli began to form and asked: (a)
Is the formation of the array of olfactory glomeruli triggered by an interaction
of the first-arriving receptor axons with the dendrites of mitral-like neurons?
(b) At the level of individual glomeruli, must the mitral-like dendrites be in
place either to maintain receptor axons in a glomerular arrangement, or to guide
later-growing dendrites of other types into the developing glomeruli? Our results
indicate that even without the participation of this group of mitral-like
neurons, the array of sexually isomorphic ordinary glomeruli forms and the basic
substructure of individual glomeruli develops apparently normally. We conclude
that the mitral-like neurons in Manduca are not essential for the formation of
ordinary olfactory glomeruli during development.
PMID- 9658338
TI - p59fyn and pp60c-src modulate axonal guidance in the developing mouse olfactory
pathway.
AB - The Src-family tyrosine kinases p59fyn and pp60c-src are localized on axons of
the mouse olfactory nerve during the initial stages of axonal growth, but their
functional roles remain to be defined. To study the role of these kinases, we
analyzed the trajectory of the olfactory nerve in E11.5 homozygous null mutant
mice lacking single src or fyn gens and double mutants lacking both genes.
Primary olfactory axons of single and double mutants exited the olfactory
epithelium and projected toward the telencephalon, but displayed differences in
fasciculation. The fyn-minus olfactory nerve had significantly more fascicles
than than src-minus nerve. Most strikingly, the primary olfactory nerve of
src/fyn double mutants showed the greatest degree of defasciculation. These
defects, identified by NCAM labeling, were not due to apparent changes in the
size of the olfactory epithelium. With the exception of the src-minus mice, which
had fever fascicles than the wild type, no obvious differences were observed in
coalescence of vomeronasal axons from mutant mice. The mesenchyme of the double
and single mutants exhibited only subtle changes in laminin and fibronectin
staining, indicating that the adhesive environment of the mesenchyme may
contribute in part to defects in fasciculation. The results suggest that
signaling pathways mediated by p59fyn and pp60c-src contribute to the appropriate
fasciculation of axons in the nascent olfactory system, and comprise partially
compensatory mechanisms for axonal adhesion and guidance.
PMID- 9658339
TI - Thrombin is an extracellular signal that activates intracellular death protease
pathways inducing apoptosis in model motor neurons.
AB - Apoptosis, often also termed "programmed cell death", occurs in normal
development in the brain and spinal cord. Important to concepts of disease and
potential intervention is the exciting finding that apoptosis is also found after
neurotrauma and in a number of neurodegenerative diseases. Although the precise
mechanism of neuronal cell loss remains unknown, much emphasis has been placed
recently on the activation of cell death protease cascades within the cell. How
these cascades may be activated, especially from extracellular influences, is
currently poorly understood. Thrombin, the multifunctional coagulation protease,
is an early phase modulator at sites of tissue injury and has been shown to
induce cell death in neurons by an apoptotic mechanism by activating its
receptor, PAR-1. Using a model motor neuronal cell line, NSC19, which we have
shown undergoes apoptosis after treatment with classic apoptosis inducers such as
the topoisomerase inhibitors camptothecin and etoposide, we unambiguously found
that nanomolar thrombin induced characteristic signs of apoptosis. Strikingly,
endonucleolysis was accompanied by an increase in caspase-3-like activity in
cellular extracts, which correlated with both detection of caspase-induced
signature cleavage of the cortical cytoskeleton component nonerythroid spectrin
(alpha-fodrin) and identification of increased accessibility of a caspase
cleavage domain, using an antibody (Ab127) made against a synthetic peptide
KGDEVD. Demonstrating that thrombin activation of death proteases was linked to
cell death, we were able to inhibit thrombin-induced apoptosis by using a caspase
family inhibitor, benzyloxycarbonyl-Asp-(oMe)-fluoromethyl ketone (Boc-D-FMK).
These novel results demonstrate that thrombin serves as an extracellular "death
signal" to activate intracellular protease pathways. These pathways lead to
apoptotic cell death and can be modulated by inhibiting caspase activity
downstream to PAR-1.
PMID- 9658340
TI - Conspecific and heterospecific song discrimination in male zebra finches with
lesions in the anterior forebrain pathway.
AB - Adult zebra finches can produce normal song in the absence of Area X, IMAN, or
DLM, nuclei that constitute the anterior forebrain pathway of songbirds. Here, we
address whether lesions involving Area X and IMAN affect adult male zebra
finches' ability to discriminate between conspecific or heterospecific songs.
Intact birds and lesioned birds were trained on an operant GO/NOGO conditioning
paradigm to discriminate between hetero- or conspecific songs. Both lesioned and
intact birds were able to learn all discriminations. Lesioned and intact birds
performed equivalently on canary song discriminations. In contrast,
discriminations involving bird's own song took significantly more trails to learn
for lesioned birds than for intact birds. Discrimination between conspecific
songs in general also took longer in the lesioned birds, but missed significance
level. Birds with control lesions medial to Area X did not show any differences
from intact animals. Our results suggest that an intact anterior forebrain
pathway is not required to discriminate between heterospecific songs. In
contrast, Area X and IMAN contribute to a male zebra finch's ability to
discriminate between its own song and that of other zebra finches.
PMID- 9658341
TI - Dynamic behavior of the ends of growing parallel fibers in early postnatal rat
cerebellum.
AB - The molecular layer of the cerebellum contains parallel fibers, the axons of
granule neurons. We have examined the morphology and behavior of parallel fiber
growth cones in the early postnatal rat cerebellum using the fluorescent tracer
DiI. Parallel fiber growth cones distributed into three categories based on size
and shape: short torpedo-like, long torpedo-like, and lamellopodial in form. The
torpedo-like growth cones were modified by the addition of lamellopodia and/or
filopodia, and the lamellopodial growth cones were often decorated with a
filopodium. These three different growth cone morphologies were found throughout
the growing region of the molecular layer. The nascent axons elaborated by
premigratory granule neurons differed form the longer axons of more developed
neurons in that they often had forked growth cones and extensive lamellopodial
decoration along the axon shaft. Growth cones in living slices closely resembled
those observed in the fixed preparations. The living growth cones exhibited
frequent lamellopodial rearrangement and a side-to-side headwaving movement. The
axon proximal to the growth cone was also dynamic. The axons curved and
undulated, and mobile swellings formed along the axon shaft. These observations
show that the growth cones of parallel fibers are similar to growth cones
described for axons in other developing systems in terms of size, morphological
characteristics, and dynamic behavior.
PMID- 9658342
TI - The effect of shoulder magnetic resonance imaging on clinical decision making.
AB - One hundred cases were prospectively evaluated to determine the impact of
magnetic resonance imaging on clinical decision making in an orthopaedic practice
devoted to the treatment of disorders about the shoulder. Each was analyzed for
changes in the clinical diagnosis or treatment. A change that either changed the
primary diagnosis or type of treatment (operative versus nonoperative) was
classified as category one. If additional clinically relevant findings were noted
on the imaging studies without altering the primary diagnosis, or if the form of
treatment was modified but not changed from operative or nonoperative, it was
considered category two. Among the 100 imaging studies reviewed, category one and
two changes were observed in 11 and 7 cases, respectively. Magnetic resonance
imaging was particularly helpful in diagnosing ganglion cysts about the shoulder,
a category one change in three out of three cases. For specific diagnoses a
category one or two change was observed in 17% (10 of 59), 29% (4 of 14), 8% (1
of 13),and 100% (2 of 2) for rotator cuff disease, glenohumeral instability,
adhesive capsulitis, and biceps disease, respectively. In 35 cases magnetic
resonance imaging was considered to be unnecessary for the diagnosis or treatment
of the patient. For the 65 patients who underwent magnetic resonance imaging,
category one and two changes were noted in 10 and 5 patients, respectively.
Statistical significance was demonstrated for category one changes in the entire
group (100 cases) and the in subgroup recommended for magnetic resonance imaging
(65 cases) (p < 0.05), indicating that the judicious use of magnetic resonance
imaging can have a significant increase its impact on clinical decision making.
Magnetic resonance imaging was found to be of limited diagnostic value in
patients with an isolated primary clinical diagnosis of adhesive capsulitis,
glenohumeral or acromioclavicular arthritis, brachial plexopathy, and cervical
degenerative disk disease.
PMID- 9658343
TI - A modification of Henry's anterior approach to the humerus.
AB - A retrospective chart review identified patients who had surgery through Henry's
standard anterior and anterolateral approaches to the humerus. Of the patients
contacted, 62% had problems with the skin incision with reports of pain,
numbness, and tingling around the scar. The frequency of cutaneous problems
including neuroma prompted an anatomic study; the lower lateral cutaneous nerve
branches to the arm were dissected in seven cadaver arms to determine their
course. Henry's incision was then compared with a midline anterior incision. The
cutaneous nerves were noticeably less numerous and smaller in diameter in the
midline incision, probably related to the internervous, or watershed zone of
cutaneous nerves in the anterior midline of the arm. Henry's standard
intermuscular humeral exposure was no more difficult with the anterior midline
incision. This study supports the notion that an anterior midline incision to
approach the shaft of the humerus would minimize scar discomfort from cutaneous
nerve injury.
PMID- 9658344
TI - Change of calcifications after arthroscopic subacromial decompression.
AB - Fifty patients were reviewed after arthroscopic subacromial decompression. Twenty
five had calcific deposits in the rotator cuff visible on x-ray evaluation. Each
patient with calcification was matched with a patient without calcification who
had a similar state of the rotator cuff, date of surgery, age, and sex. The
calcific deposits were left untouched in all cases. No significant difference was
found in the postoperative outcome between the patients in the two groups
measured by the Constant score. Before surgery 7 (28%) patients had
calcifications of < 5 mm, and 18 (72%) patients had calcifications that were > or
= 5 mm. At a 2-year follow-up (n = 24) these figures were 20 (83%) and 4 (17%),
respectively (p < 0.001). Postoperative x-ray evaluations revealed a
disappearance or decrease in size of the calcific deposits in 19 (79%) of the
patients. These results provide new information on the course of calcifying
tendinitis, which may indicate that we can leave calcific deposits untouched
within the rotator cuff when performing arthroscopic subacromial decompression.
PMID- 9658345
TI - Frozen shoulder: arthroscopy and manipulation under general anesthesia and early
passive motion.
AB - During a 15-month period, 24 patients with arthroscopically verified frozen
shoulders were treated with manipulation while under general anesthesia and early
passive motion. The minimum follow-up was 12 months, and the average duration
from onset of the disease until treatment was 8 months. All patients had moderate
to severe pain, and the average range of motion was less than 40% of the opposite
shoulder. During the follow-up period, 75% of the patients obtained normal or
almost full range of motion, and 79% had slight pain or no pain at all. Eighteen
(75%) patients returned to work 9 weeks (mean) after treatment. There was no
relationship between the end result and the initial pathologic condition. We
believe that manipulation combined with arthroscopy is an effective way of
shortening the course of an apparently self-limiting disease and should be
considered when conservative treatment has failed.
PMID- 9658346
TI - Magnetic resonance imaging of suprascapular nerve palsy.
AB - In magnetic resonance imaging of peripheral nerve palsy, changes of signal
intensity are often found in paralyzed muscles. The purpose of this report is to
clarify the relation between magnetic resonance imaging findings and clinical
examination in suprascapular nerve palsy. The subjects were 12 patients with
suprascapular nerve palsy who underwent magnetic resonance imaging examinations.
In 9 of 12 cases ganglion cysts were found at the spinoglenoid notches. On T1
weighted images the signal intensity of infraspinatus muscle was high in four
cases but normal in the supraspinatus muscle in all cases. On T2-weighted images
the signal intensity of infraspinatus muscle was high in six cases, and that for
supraspinatus muscle was high in one case. In two cases the high intensity of
palsied muscles became normal after the palsy recovered. Magnetic resonance
imaging is a useful examination of peripheral nerve palsy not only for the
detection of ganglion cysts but also for assessing the stage of paralysis.
PMID- 9658347
TI - Self-assessment of general health status in patients with five common shoulder
conditions.
AB - The SF-36 Health Survey is a patient self-administered general health status
evaluation designed to measure the impact of disease on an individual's
perception of his or her health. Five hundred forty-four patients with five
common shoulder conditions (anterior glenohumeral instability (149 patients),
complete reparable rotator cuff tear (111 patients), adhesive capsulitis (100
patients), glenohumeral osteoarthritis (67 patients), and impingement (117
patients)) completed the SF-36 Health Survey before undergoing treatment. When
compared with U.S. general population norms, the patients with each of these
shoulder conditions had statistically significant decreases in their health for
Physical Functioning, Role-Physical, Bodily Pain, Social Functioning, Role
Emotional, and the Physical Component Summary as measured by the SF-36 Health
Survey. Comparison with published data demonstrated that these shoulder
conditions rank in severity (in terms of affecting a patient's perception of his
or her general health) with five major medical conditions (hypertension,
congestive heart failure, acute myocardial infarction, diabetes mellitus, and
clinical depression). The data presented in this study should serve as a baseline
to document the impact of shoulder musculoskeletal conditions and possibly to
allow comparison among various methods of operative and nonoperative treatment.
PMID- 9658348
TI - The spinoglenoid ligament and its relationship to the suprascapular nerve.
AB - Entrapment of the suprascapular nerve by the inferior transverse scapular
ligament or spinoglenoid ligament (SGL) has been discussed frequently in the
literature, but it has not been well documented anatomically. Therefore the
mechanism of entrapment is not well understood. When isolated atrophy and
denervation of the infraspinatus muscle have been noted, compression of the
muscle's motor branch at the spinoglenoid notch has been implicated. This
anatomic and morphologic study investigates the role of the SGL in entrapment
neuropathy of the infraspinatus. We used 23 shoulders from 19 cadavers, 5 women
(8 shoulders) and 14 men (15 shoulders), with a mean age of 67.9 (54 to 78)
years. The presence or absence of the SGL was noted. The length, width, and
orientation of the SGL; size and shape of the tunnel to the infraspinatus fossa;
and distance of the notch to the posterior glenoid rim were determined. The SGL
was present in 14 (60.8%) shoulders, 5 (36%) women and 9 (64%) men. The SGL was
wider at the superior entrance of the tunnel and fanned and twisted toward the
inferior aspect. In all specimens the SGL fibers inserted into the posterior
shoulder capsule. The mean length for the upper part of the SGL was 17.5 +/- 2.6
mm in men and 15.8 +/- 1.8 mm in women, and the lower part was 14.1 +/- 2.4 mm
and 12.9 +/- 1.8 mm, respectively. The widths of the SGL at the origin of the
scapular spine were 12.2 +/- 3.9 mm for men and 10.4 +/- 2.7 mm for women,
whereas the insertion site widths were 15.8 +/- 2.2 mm for men, and 16.1 +/- 3.8
mm for women. The midportion width of the SGL was 6.8 +/- 1.9 mm in men and 5.8
+/- 2.1 mm in women. During cross-body adduction and internal rotation of the
glenohumeral joint, the interaction of the SGL and the posterior capsule resulted
in a tightening of the SGL. The suprascapular nerve moved laterally and stretched
underneath the SGL in this position.
PMID- 9658349
TI - Rehabilitation after subcutaneous transposition of the ulnar nerve: immediate
versus delayed mobilization.
AB - We studied 36 patients who had clinical signs and symptoms consistent with
cubital tunnel syndrome and in whom nonoperative management failed. These
patients underwent anterior subcutaneous transposition of the ulnar nerve
followed by either immediate (20 patients) or delayed (16 patients) mobilization.
All patients were evaluated with an outcomes assessment questionnaire, and 35 of
the 36 were given repeat physical examinations. After surgery, there were no
significant differences between the two groups in pain relief, weakness, or
patient satisfaction (71% of the immediate mobilization group and 74% of the
delayed group) were satisfied. Secondary quantitative outcomes such as grip
strength, lateral pinch, or two-point discrimination were also not significantly
different between the groups. Both groups had a statistically significant
improvement in first dorsal interosseous and adductor pollicis muscle strength.
In the immediate mobilization group, however, patients returned to work and
resumed activities of daily living earlier (median 1 month) than patients in the
delayed mobilization group (median 2.75 months). Therefore, we conclude that
anterior subcutaneous transposition provides a high degree of satisfaction and
relief of symptoms regardless of when mobilization is initiated. However,
immediately mobilizing the patient significantly influenced how early the patient
returned to work and resumed activities of daily living.
PMID- 9658350
TI - Musculocutaneous nerve entrapment revisited.
AB - Compression of the lateral cutaneous nerve of the forearm (LCNF), the distal
sensory termination of the musculocutaneous nerve, can occur below the biceps
aponeurosis, most commonly after strenuous elbow extension or forearm pronation.
Between 1965 and 1992, 15 patients reported pain in the anterolateral elbow with
"burning" into the forearm. There was a minimum 2-year follow-up of all patients
in the study (average 13.4 years, median 15 years). All patients were managed
conservatively for 12 weeks. Of the 15 patients, 11 required operative
decompression that involved resecting a triangular wedge of aponeurosis overlying
the nerve. Of the four nonoperative patients, one had persistent hypesthesia even
though pain was relieved and range of motion was restored. Of the 11 patients
treated operatively, none had recurrence of hypesthesia, and all patients
continued to have complete relief of pain and full range of motion. One
additional patient required surgery for lateral epicondylitis 2 years later.
There were no operative complications.
PMID- 9658351
TI - Electromyographic analysis of shoulder function during the volleyball serve and
spike.
AB - The purpose of this study was to describe the electromyographic (EMG) pattern and
relative intensities of 8 shoulder muscles during the volleyball serve and spike
in 15 professional or collegiate-level athletes. The EMG analysis was
synchronized with high-speed cinematography to discern phases of the spike and
serve. During the spike, the anterior deltoid and supraspinatus functioned
together to elevate and place the humerus throughout all phases. During cocking
the infraspinatus and teres minor acted together to rotate the humerus
externally. In acceleration, however, these muscles behaved independently;
activity of the teres minor remained high, whereas the activity of the
infraspinatus declined. The anterior wall muscles functioned to decelerate the
humerus during cocking and acted as internal rotators during acceleration. Muscle
activities recorded for the serve followed similar patterns as those seen for the
spike, but with lower amplitudes. These data illustrate the complex sequence of
shoulder muscle activity necessary to play competitive volleyball.
PMID- 9658352
TI - Shoulder ultrasound: diagnostic accuracy for impingement syndrome, rotator cuff
tear, and biceps tendon pathology.
AB - We sought to determine the accuracy of ultrasound for the preoperative evaluation
of shoulder impingement syndrome, rotator cuff tear, and abnormalities of the
long head of the biceps tendon. The findings in 42 consecutive surgical cases
were compared with the preoperative sonographic readings. Ultrasound detected all
of the 10 full-thickness cuff tears identified at surgery (sensitivity 1.0,
specificity 0.97) but detected only 6 of 13 partial-thickness cuff tears
(sensitivity 0.46, specificity 0.97). A full-thickness tear was falsely diagnosed
in one case of severe cuff abrasion. Dynamic scan criteria correctly diagnosed
impingement in 27 of 34 cases (sensitivity 0.79, positive predictive value 0.96).
Abnormalities of the long head of the biceps were accurately diagnosed with the
exception of low-grade tendinitis and the superior labral tear, anterior to
posterior, lesion. We concluded that ultrasound is a sensitive and accurate
method of identifying patients with full-thickness tears of the rotator cuff,
extracapsular biceps tendon pathology, or both. Dynamic ultrasound can help
confirm, but not exclude, a clinical diagnosis of impingement.
PMID- 9658353
TI - Hyperextension of the elbow joint: pathoanatomy and kinematics of ligament
injuries.
AB - According to an epidemiologic study (Scand J Med Sci 1996/ 6: 297-302) the
mechanism of "handball goalie's elbow" may be forced hyperextension. The
pathomechanics of hyperextension were studied in nine macroscopically normal male
cadaver elbow joints. The mean age of the donors was 43.2 years (range 25 to 61
years). Kinematic tests were performed with an experimental three-dimensional
kinematic loading apparatus. Hyperextension loads induced joint laxity during
flexion of less than 50 degrees. The kinematic changes were significant in joint
flexion during forced valgus and external and internal axial rotation, but were
not significant in flexion during forced varus. No instability was found with
flexion beyond 90 degrees. The hyperextension loads produced four lesions: (1)
anterior capsule rupture; (2) L-shaped rupture of the pronator/flexor origin with
elongation of the anterior part of the medial collateral ligament; (3) occasional
incomplete rupture of the lateral collateral ligament; and (4) small fragments of
cartilage near the posterior edge of the ulna in one of the specimens. One or
more of these lesions may be responsible for the symptoms in "handball goalie's
elbow."
PMID- 9658354
TI - Anthropometry of the scapula: clinical and surgical considerations.
AB - Anthropometric measurements were taken on 266 scapulas from the "G. Marro"
Egyptian skeletal collection of the Department of Anthropology of the University
of Turin in Italy to study the orthopaedic pathologic condition of the shoulder
joints. Data were taken on the size and shape of the acromial arch in relation to
the inclination and anatomic variants of the acromion. The rarity of the "hooked"
form was confirmed, and two variants of the acromial vault (i.e., one
predominantly osseous and the other predominantly fibrous) were recognized. The
spatial location and biomechanical importance of the coracoid process were
considered. Orientation of the glenoid fossa furnishes an osseous base for the
stability of the scapulohumeral joint both anteroposteriorly and vertically.
Observations on current practices of surgical intervention on the shoulder as
reported in the literature and some anatomic skeletal basis of surgical access
are discussed.
PMID- 9658355
TI - Axillary artery injury as a complication of proximal humerus fractures.
AB - Proximal humerus fractures are common injuries and represent approximately 5% of
all fractures. These fractures are infrequently associated with neurovascular
injuries. Brachial plexus injuries are uncommon, whereas axillary artery injuries
are rare. A review of 19 previously reported cases of axillary artery injury
after proximal humerus fracture revealed that 84% occurred in patients older than
50 years, 53% were associated with brachial plexus injury, and 21% resulted in
upper extremity amputation. This study describes a case of axillary artery injury
after proximal humerus fracture and, on the basis of a literature review, offers
suggestions for the early diagnosis and effective treatment of this uncommon
injury.
PMID- 9658356
TI - A rare variation of the biceps: a possible cause of degeneration of the rotator
cuff.
PMID- 9658357
TI - Deltoid contracture exhibiting anterosuperior subluxation of the shoulder joint.
PMID- 9658358
TI - HIV/AIDS funding: we still need it.
PMID- 9658359
TI - Hazardous terrain and over the edge: the survival of HIV-positive heterosexual,
minority men.
AB - The purpose of this study was to describe and explore the experience and
perceptions of heterosexual minority men living with and surviving HIV infection.
This descriptive, exploratory qualitative study used in-depth interviews that
were guided by Rosenstock's health belief model and Ajzen's theory of planned
behavior. A purposive sample of 18 HIV-positive heterosexual, minority men were
accrued from an outpatient HIV/AIDS clinic in upstate New York and a community
based AIDS service organization in New York City. The findings revealed that the
experience of surviving HIV infection encompassed several stages. The men of this
study described the choices they made in adolescence that led them down a trail
of life that may be metaphorically described as "hazardous terrain," as the
majority became involved in substance use or other illicit activities. With the
diagnosis of HIV infection came a "Falling Off" stage, in which the participants
went "over the edge" and initially were afraid to die but realized at this point
that they were okay but vulnerable. The next stage was "Hanging On," in which
they attempted to gain control, reevaluated priorities, and developed a new
perspective on life and health. In the "Pulling Up" stage, participants realized
that the rescue team included self, God, family, and friends, with self-rescue
occurring on emotional, physical, and spiritual levels. As the participants
reached the "Turning Around" stage, they began to accept responsibility for their
health, focused on their abilities rather than their limitations, and reframed
their perspectives to living with rather than dying from HIV infection. This
study has implications for health-education programs, AIDS prevention, health
assessment, and interventions for HIV-positive, heterosexual, minority men.
PMID- 9658360
TI - Support groups for people living with HIV/AIDS: a review of literature.
AB - For more than a decade, support groups have been proposed as a key intervention
for people living with HIV and AIDS (PLWAs). Despite this fact, there are still
only a few articles that evaluate and compare outcomes of support groups so as to
provide a scientific base for their usefulness and effectiveness. The purpose of
this article is to critically review selected published literature on support
groups and to assess gaps in research. In general, the reviewed literature
evaluated support groups as an effective intervention, which is evident for this
widespread support. However, because diverse populations of PLWAs have specific
needs, the group and intervention should be designed to meet those needs.
Specific recommendations for further research about support groups for PLWAs are
offered.
PMID- 9658361
TI - Rosehedge: a home health agency and adult family home.
PMID- 9658362
TI - Therapeutic touch with HIV-infected children: a pilot study.
AB - In this pilot study, 20 HIV-infected children, 6 to 12 years of age, were
randomly assigned into therapeutic touch (TT) and mimic TT groups. The
effectiveness of TT in reducing anxiety was evaluated. The self-report measure,
the A-State Anxiety subscale of the Spielberger State-Trait Anxiety Inventory For
Children, was administered before and immediately after interventions. As
predicted, the TT intervention resulted in lower overall mean anxiety scores,
whereas the mimic TT did not. These findings provide preliminary support for the
use of TT in reducing the state anxiety of children with HIV infection.
PMID- 9658363
TI - Cortisol upregulates HIV p24 antigen production in cultured human monocyte
derived macrophages.
AB - HIV infection is associated with hypercortisolemia. Since glucocorticoids have
been shown to stimulate the replication of several viruses, we examined the
effects of cortisol on HIV replication in cultured monocyte-derived macrophages
(MDM), a cell type that has been proposed to serve as a viral reservoir. Our data
revealed that physiological concentrations of cortisol upregulate viral
replication in MDM. Because the dose-response curve for cortisol on HIV
replication in vivo is not known, the clinical relevance of these findings remain
uncertain. Clinical studies are needed to characterize the effects of
corticosteroid therapy on viral burden in vivo.
PMID- 9658364
TI - The reliability and validity of the subjective peripheral neuropathy screen.
AB - Painful sensory neuropathy (PSN) is the most common neurological disorder
associated with HIV infection and affects up to 30% of HIV-positive individuals.
PSN may develop as a consequence of HIV infection or from the toxic effect of the
antiretrovirals. Although several tools have been developed to screen for PSN,
their validity and reliability has yet to be established among HIV-positive
patients. The Subjective Peripheral Neuropathy Screen (SPNS) is a brief self
report tool that is currently being administered in the AIDS Clinical Trials
Group. The objective of this study was to establish the psychometric properties
of the SPNS screening tool for the correct identification of PSN in HIV-positive
individuals. Specifically the goals were to determine the reliability, the
validity, and the diagnostic efficiency of the SPNS in the detection of PSN. Data
were abstracted on subjects enrolled in an ongoing natural history cohort. The
SPNS was administered to a convenience sample of 39 HIV-positive individuals with
PSN and 44 HIV-positive controls. Results showed the SPNS to be internally
consistent (Cronbach's alpha = .86). SPNS score differences assessed by t-test
were significantly different for individual symptoms of parasthesias, numbness,
and pain of the lower extremities, and for severity measures (the Clinical
Severity Grade, and the Average Severity Score) between the HIV-positive groups
(p < .05). Using Spearman's rank, significant correlations were demonstrated
between the neurological exam and the Clinical Severity Grade and the Average
Severity Score, the neurological exam and vibratory quantitative sensory testing
(QST) only, and the severity measures and vibratory QST only. Sensitivity and
specificity analysis demonstrated that numbness of the lower extremities was the
symptom with the highest efficiency for correctly classifying PSN. Thus, internal
consistency, construct validity, and criterion related validity were confirmed
with the SPNS for the correct classification of PSN in HIV-positive individuals.
PMID- 9658365
TI - Managing fever in HIV disease.
PMID- 9658366
TI - Are all type I human interferons equivalent?
AB - The Type I interferons are a family of closely related cytokines that have
antiviral and immunostimulatory properties. There has been prolonged debate
regarding the different interferon-alpha subtypes: with some authorities suggest
that the different interferons have essentially similar properties but others
argue that there are significant differences between them. Recent work has shown
that the various interferon-alpha subtypes can interact with the interferon
receptor components in different ways and can activate a number of different
signalling pathways. Recent studies on the immunomodulatory properties of the
Type I interferons indicate that there are profound differences between the
subtypes. The clinical significance of all these differences remains to be
determined.
PMID- 9658367
TI - Evolution of hepatitis G virus infection and antibody response to envelope
protein in patients with transfusion-associated non-A, non-B hepatitis.
AB - The clinical significance and course of acute hepatitis G virus (HGV) infection
were studied by measuring HGV RNA and antibody to HGV envelope protein E2 (HGV-E2
antibody). A total of 59 patients with transfusion-associated non-A, non-B
hepatitis, who were followed-up for more than 1 year, were selected
retrospectively. HGV RNA was measured by reverse transcriptase (RT) and nested
polymerase chain reaction (PCR) was performed, using primer sets, in the 5'-non
coding region of the HGV genome. HGV-E2 antibody was measured by enzyme-linked
immunosorbent assay (ELISA) using recombinant E2 protein. Of the 59 patients, 51
(86%) were infected with hepatitis C virus (HCV) and 12 (20%) were infected with
HGV; 11 of the 12 with HGV infection were also infected with HCV. HGV viraemia
was cleared during the follow-up period in seven of the 12 patients with HGV
infection. All these seven patients seroconverted for HGV-E2 antibody just before
or just after the clearance of HGV viraemia. In contrast, all five patients
without clearance of HGV viraemia were negative for HGV-E2 antibody (P = 0.0013).
Of seven patients with continuous HGV viraemia at 1 year from the onset of acute
hepatitis, four with HCV RNA showed chronic elevation of alanine aminotransferase
(ALT) but three without HCV RNA did not. The severity of acute hepatitis was
similar between patients with both HGV and HCV infections and in those with HCV
infection alone. The majority of patients with HGV infection cleared the virus
during long-term follow-up. Appearance of HGV-E2 antibody was associated with the
clearance of HGV viraemia. An abnormal ALT level was noted to depend on HCV
infection but not on HGV infection in both the acute and chronic phases of
transfusion-associated hepatitis.
PMID- 9658368
TI - Detection of hepatitis G virus RNA in patients with acute non-A-E hepatitis.
AB - We investigated the possible role of hepatitis G virus (HGV or GBV-C) in the
aetiology of acute non-A-E hepatitis in Argentina by detecting viral RNA in sera
by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers
specific for the putative NS3 helicase region of HGV. Sixty two patients with
acute hepatitis were included in this study. The absence of hepatitis A-E was
confirmed by serological testing, and all patients were negative for HCV RNA and
autoimmune markers. All patients denied alcohol intake and the use of hepatotoxic
drugs. Their mean age was 35.3 years and 37 were males. HGV RNA was present in
19/62 (30.6%) of the patients with non-A-E acute hepatitis. Among HGV-positive
patients, three had parenteral risk factors within 3 months of onset, one was a
health care worker, one was sexually promiscuous, one had travelled to the Middle
East and 13 (68.4%) had no history of parenteral exposure. Epidemiological,
clinical and biochemical features between HGV-positive and negative patients did
not achieve statistical significance. Hence, HGV appears to play a role in the
pathogenesis of acute viral hepatitis; however, the etiology of a significant
number of hepatitis cases remains unclear, suggesting the existence of an
additional agent(s). The absence of parenteral exposure in most of the HGV RNA
positive patients in this study shows that routes of community-acquired HGV
infection are not yet completely understood.
PMID- 9658369
TI - Hepatitis G infection: role in cryptogenic chronic liver disease and primary
liver cell cancer in the UK. Trent Hepatitis C virus Study Group.
AB - Hepatitis G virus (HGV) is a flavivirus that can cause acute hepatitis and
persistent infection but its role in chronic liver disease or primary liver
cancer is unproven. In this study we have examined the prevalence of HGV RNA in
the serum of patients with hepatitis C virus (HCV) infection and in patients with
cryptogenic chronic liver disease, including non-alcoholic steatohepatitis
(NASH), and in patients with HCV-related hepatocellular carcinoma (HCC) and HCC
arising in patients with cryptogenic liver disease. One-hundred and thirty
patients who were positive for antibody to HCV (anti-HCV), 54 patients with
cryptogenic chronic liver disease (including 17 patients with NASH) and 46
patients with hepatitis C-related (n = 27) or cryptogenic liver disease-related
HCC (n = 19) were studied. HGV RNA was detected using nested reverse
transcriptase-polymerase chain reaction (RT-PCR) and was found in 16.1% of
patients with HCV infection. HGV RNA was not detected in any patient with
cryptogenic liver disease. In patients with HCC, 7/34 samples were positive for
HGV RNA and six out of seven HGV-positive subjects also had HCV infection. Only
one patient with HCC in cryptogenic liver disease was positive for HGV RNA.
Hence, cryptogenic liver disease in the UK is not caused by HGV/GBVc infection.
It seems unlikely that HGV plays a significant role in hepatocarcinogenesis.
PMID- 9658370
TI - Predictive value of aminotransferase and hepatitis B virus DNA levels on response
to interferon therapy for chronic hepatitis B.
AB - In a previously reported randomized controlled trial of interferon-alpha (IFN
alpha) for chronic hepatitis B, we found a significant difference in response
between Chinese adults with elevated vs normal pretreatment aminotransferase
(ALT) levels. The aim of this study was to determine the correlation between
serum hepatitis B virus (HBV) DNA levels and response to IFN therapy. HBV DNA
levels in residual stored sera from patients who participated in the above trial
were quantified by a branched DNA (bDNA) assay. Nominal logistic regression was
used to estimate the probability of response to IFN treatment as a function of
pretreatment ALT and/or HBV DNA levels. We found a significant (P < 0.01)
correlation between the HBV DNA levels at midtreatment and response to IFN
therapy. Response was achieved in 53% of patients who had undetectable HBV DNA
levels at midtreatment but in only 17% of those who remained HBV DNA positive (P
< 0.01). In contrast, the probabilities of response for patients with baseline
HBV DNA levels over the range 10 to 10000 million equivalents (MEq) ml-1 were
almost identical. We also found a significant correlation between the
pretreatment ALT levels and response to IFN therapy. The probabilities of
response for patients with pretreatment ALT levels of 500 and 100 IU l-1 were
higher than for patients with normal ALT levels by two and onefold, respectively.
Our findings may help to improve the cost-effectiveness of IFN therapy for
chronic hepatitis B by guiding the selection of patients for therapy and in
optimizing the duration of treatment for the individual patient.
PMID- 9658371
TI - Systemic manifestations and liver disease in patients with chronic hepatitis C
and type II or III mixed cryoglobulinaemia.
AB - The aim of this study was to evaluate the prevalence of cryoglobulins in patients
with chronic hepatitis B and C virus infection and to investigate the association
of type II and type III mixed cryoglobulinaemia with systemic manifestations and
liver disease stage and outcome in hepatitis C virus (HCV)-positive patients. We
analysed the prevalence of cryoglobulinaemia in a cohort of patients with chronic
liver disease and compared the systemic manifestations and liver involvement in
HCV-positive patients with type II or type III mixed cryoglobulinaemia. The
prevalence of serum cryoglobulins was significantly higher in HCV-positive
patients than in hepatitis B surface antigen (HBsAg)-positive patients (55.4 vs
20.6%). In HCV-positive patients, stage of liver disease correlated with the
prevalence of cryoglobulinaemia. Patients with type II cryoglobulins showed a
significantly higher risk of cirrhosis and of extrahepatic manifestations while
patients with type III cryoglobulins had a significantly higher prevalence of
hepatocellular carcinoma. During follow-up the former had an odds ratio of 11.9
of death from extrahepatic complications while the latter had an odds ratio of
3.4 of dying from hepatic disease. Our study confirms the high frequency of mixed
cryoglobulinaemia in patients with chronic hepatitis C virus infection. The
presence and type of cryoglobulins seem to be associated with different clinical
manifestations and outcome.
PMID- 9658372
TI - Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C
virus infection.
AB - Patients with chronic hepatitis C virus (HCV) infection are often asymptomatic
with few clinical signs of liver disease. Recognition of the presence of fibrosis
or cirrhosis is difficult without liver biopsy, but with the availability of
effective treatments, such as interferon, and the potential for progression to
hepatoma in some cases, an accurate measure of the stage of disease is important.
Serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis
or cirrhosis in other settings. In a prospective study in 130 chronic HCV
carriers therefore, serum HA concentrations were compared with conventional liver
function tests (including alanine aminotransferase (ALT), a-glutathione-S
transferase (GST) and serum HCV RNA in order to determine which identified the
stage of liver fibrosis as assessed by liver biopsy most accurately. The median
HA concentrations according to the stage of fibrosis 0, 1 & 2, 3 and 4 & 5 were
17 g l-1 (range 5-37), 17 g l-1 (5-80), 30 g l-1 (10-105) and 350 g l-1 (20-800)
respectively. The median HA concentration in stage 4 & 5 was significantly
greater than in stages 0, 1 & 2 or 3. Serum HA concentration rose with age, but
even when adjusted for age the median HA at stage 4 & 5 was greater than all
other groups (95% CI of difference between the medians exceeded 0). Thus, serum
HA gave a sensitivity and specificity for stage 4 & 5 fibrosis of 85% and 88%
respectively, exceeding those for ALT or GST. In contrast, serum ALT or GST
levels were not correlated with the stage of fibrosis although ALT was
significantly greater in the cirrhotic group when compared to the group with no
fibrosis (stage 0). There was no correlation between serum HA and either the
grade of inflammatory changes or serum HCV RNA. These results suggest that serum
hyaluronic acid is a useful marker of liver fibrosis in patients with chronic HCV
infection. It could therefore be used to monitor patients at risk of progressive
fibrosis, in controlled clinical trials, as a measure of response to antifibrotic
therapy and in those in whom liver biopsy is difficult or contraindicated.
PMID- 9658373
TI - Ribavirin monotherapy in patients with chronic hepatitis C: a retrospective study
of 95 patients.
AB - Ribavirin is a purine nucleoside that inhibits the replication of a variety of
RNA viruses and was shown to have a transient efficacy in chronic hepatitis C
during short-term therapy. We have analysed retrospectively its efficacy in 95
patients with liver biopsy-proven chronic hepatitis C. Patients received oral
ribavirin (600-1200 mg daily) for a mean duration of 11 months. Alanine
aminotransferase (ALT) levels returned to normal values in 38 patients (40%) and
decreased by more than 50% in 20 other patients (21%). HCV RNA clearance from
serum was observed in seven patients (8%). The biochemical response rate was
higher in patients with chronic hepatitis (54%) than in those with cirrhosis
(24%) (P = 0.003). Clearance of HCV RNA was observed in 10% of the patients with
chronic hepatitis vs 4% of the patients with cirrhosis. In non-responders to
interferon (IFN) therapy, ALT levels returned to normal values in 11 (26%) and
HCV RNA became negative in one (2%), as compared to 48% and 3%, respectively, in
those contraindicated for IFN. In 17 patients in whom paired liver biopsy
specimens were available, the histology activity index (HAI) improved in 12.
Therapy was generally well tolerated although 11 patients had to stop therapy
because of side-effects, which were more common in cirrhotic patients. In
conclusion, our results suggest that long-term administration of ribavirin is
well tolerated and may be beneficial in controlling the progression of chronic
hepatitis C. This may represent an alternative therapy in patients who have
contraindications for interferon therapy or as a palliative approach in non
responders to IFN.
PMID- 9658374
TI - Role of immune serum globulins in pregnant women during an epidemic of hepatitis
E.
AB - The efficacy of an Indian preparation of immune serum globulins (ISG) was
evaluated among pregnant women during an epidemic of hepatitis E in Karad,
Western India from January to March 1993. Ten of 55 women receiving ISG developed
immunoglobulin M (IgM) antibodies to hepatitis E virus (anti-HEV) during the 1
month of follow-up compared with 18 out of 53 control subjects. Although the
total number of recent HEV infections was significantly less in the ISG-treated
group, no significant difference could be shown in the proportion of clinical
hepatitis E cases because of the very small numbers of patients who developed
clinical disease. The observed marginal beneficial effect of ISG might be the
result of a low immunoglobulin G (IgG) anti-HEV IgG titre (1:500) of the ISG
preparation used. Preparation and testing of high-titred ISG should be a high
priority for protecting pregnant women during epidemics of hepatitis E.
PMID- 9658375
TI - Production of antibody to hepatitis A virus and hepatitis B surface antigen
measured after combined hepatitis A/hepatitis B vaccination in 242 adult
volunteers.
AB - Two batches of a new hepatitis A/hepatitis B combined vaccine were tested in 242
healthy students. Three injections, given at 0, 1 and 6 months, produced
seroconversion rates and hepatitis A virus (HAV) and hepatitis B surface antigen
(HBsAg) antibody levels comparable to those reported after administration of
separate monocomponent vaccines. The vaccine proved to be safe and well
tolerated. Influence of host factors, such as elevated body mass index or gender,
were investigated and proven to be of little influence on the immunoresponse.
PMID- 9658376
TI - A novel in vitro model to screen steroid 5 alpha-reductase inhibitors against
benign prostatic hyperplasia.
AB - A convenient and rapid in vitro model to screen steroid 5 alpha-reductase
inhibitors, which are effective in the treatment of benign prostatic hyperplasia
(BPH), was developed. In the presence of nicotinamide adenine dinucleotide
phosphate (NADPH), steroid 5 alpha-reductase converts testosterone to
dihydrotestosterone (DHT) which is a major etiologic factor of BPH. NADPH has
characteristic absorbance at 340 nm, and the absorbance spectrum may be used to
identify NADPH as a kind of the substrate in this enzymatic reaction. In this
paper, NADPH, steroid 5 alpha-reductase, series concentration of testosterone and
finasteride, and 4 ml Tris-HCl buffer were continuously incubated together at 37
degrees C and the NADPH OD values were continually measured. The descending rate
of NADPH OD340nm value by linear regression from the beginning to the 10th minute
is close to the initial velocity of the enzymatic reaction. The precise activity
of the steroid 5 alpha-reductase was the slope after subtracting that of the
blank control. The inhibition constant (Ki) of steroid 5 alpha-reductase
inhibitors could be calculated according to the Lineweaver-Burk plots. Two drug
screening models, the most common isotope model and the novel model, were
compared in this paper. The result showed that the latter one is more economical,
quicker and more effective than the former one.
PMID- 9658377
TI - Transformation of bisphosphonates into insoluble material in human blood in
vitro.
AB - The aim of the study was to find out whether bisphosphonates transform into
insoluble material in human blood and serum in vitro. Samples of fresh blood and
serum were incubated with various concentrations of 14C-labelled clodronate,
etidronate, pamidronate and tiludronate for 2 h and 8 h at 37 degrees C. The
presence of unfiltrable material in the plasma separated from the blood, and in
the serum were studied with 1) 100, 300 and 1,000 kd (kilo Daltons) filter tubes
centrifuged at 3,000 g for 60 min, and 2) high-speed centrifugation at 13,000 g
for 30 min. The radioactivities in the ultrafiltrates and supernatants were
compared to those in the native plasma or serum. All bisphosphonates transformed
into unfiltrable material, which was separated from the samples with the 100 and
300 kd filters but not with the 1,000 kd filter. The material was not sedimented
with the high-speed centrifugation. The lengthening of the incubation time from 2
h to 8 h increased the unfiltrable fraction, which generally was dependent on the
drug concentration in the blood, too. However, the fraction of the unfiltrable
material did not seem to increase with time when the drug was incubated with
serum instead of blood. Since drug binding to plasma proteins is generally a very
rapid process, some factors other than proteins only, e.g. cations or cation
residues, present in the blood but not in the serum, should be involved in
transforming of bisphosphonates into insoluble material in the blood.
PMID- 9658378
TI - Propofol concentrations in whole blood: influence of anticoagulants and storage
time.
AB - Blood samples for propofol determination are collected with oxalate, heparin and
EDTA, but we have not found any study comparing the influence of those
anticoagulants on propofol concentrations. This study was carried out on 50
samples from patients taking propofol for anesthesia or cerebral protection.
First, 26 samples were simultaneously collected into tubes containing lithium
heparin or sodium fluoride potassium oxalate as anticoagulant. In a second
investigation, 24 samples were simultaneously collected into tubes containing
heparin or EDTA. Propofol was assayed by HPLC 2 days after sampling and 2 weeks
later. In the first assay, propofol concentration in samples collected with
heparin were similar to those collected with oxalate (3.65 +/- 3.50 vs. 3.62 +/-
3.49 mg/l, ns) or EDTA (3.89 +/- 2.58 vs. 3.84 +/- 2.67 mg/L, ns). After storing
for 2 weeks at 4 degrees C, propofol concentrations were slightly but
insignificantly higher than in the first assay in samples collected with heparin
(3.58 +/- 3.24 vs. 3.40 +/- 2.92 mg/l, ns), slightly higher in samples with
oxalate (3.86 +/- 3.49 vs. 3.62 +/- 3.49 mg/l, p = 0.06), and slightly but
significantly lower in samples with EDTA (3.63 +/- 2.67 vs. 3.84 +/- 2.67 mg/l, p
< 0.05). It is concluded that the three anticoagulants used in this study seem to
be suitable for determination of propofol concentration in whole blood, and that
the stability of propofol concentration when samples are stored at 4 degrees C
for up 2 weeks is acceptable.
PMID- 9658379
TI - Effect of N-acetylcysteine on the oxidative burst induced by phagocytosis of
bacteria in human leukocytes.
AB - The basal peroxide production and the oxidative burst induced by phagocytosis of
opsonized E. coli was studied by flow cytometry using dihydrorhodamine 123. The
human leukocytes were incubated in the absence and presence of N-acetylcysteine.
The oxidative response to the phagocytosis of bacteria differed among cell
populations. Thus, 90% of granulocytes and 50% of monocytes showed an oxidative
burst in response to opsonized bacteria while less than 1% of lymphocytes showed
a fluorescence signal. N-Acetylcysteine (4.7, 9.5, 19, 38 or 76 mM) produced a
dose-dependent inhibition of the oxidative response to phagocytosis in the three
cellular populations reaching almost complete inhibition for 76 mM. This
protective effect of N-acetylcysteine against oxidative stress in leukocytes was
obtained without cytotoxicity (assessed by flow cytometry with staining with
propidium iodide) or changes in the pH of the medium. These results give further
support to the antioxidant effect of N-acetylcysteine in human peripheral blood
cells.
PMID- 9658380
TI - Cognitive involvement by negative modulation of histamine H2 receptors in passive
avoidance task in mice.
AB - In this study, the intracerebroventricular administration of 4-methylhistamine (3
and 10 micrograms/head), a histamine H2 receptor agonist, shortened the step
through latency in the retention trial using a step-through passive avoidance
task in mice. This deteriorating effect of 4-methylhistamine (3 micrograms/head)
was clearly antagonized by pretreatment with zolantidine (10 mg/kg, i.p.), a
histamine H2 receptor antagonist, 20 min before an acquisition trial. Zolantidine
alone at the dose tested had no effect. Thus, it is likely that activation of
histamine H2 receptors has a deteriorating effect on avoidance learning in mice.
The present results indicate the cognitive involvement by negative modulation of
histamine H2 receptors in passive avoidance task in mice.
PMID- 9658381
TI - Evidence of GABAergic modulation in melatonin-induced short-term memory deficits
and food consumption.
AB - Many of the pharmacological effects of melatonin have been found to be similar to
those of benzodiazepines. In the present study, we analyzed the role of melatonin
on short-term memory retrieval on transfer latency in elevated plus maze and food
consumption behavior, and the effects were compared with those of diazepam.
Melatonin dose-dependently (10-100 mg/kg) produced short-term memory deficit and
it potentiated diazepam- (1 mg/kg) induced cognitive deficit in mice. Flumazenil
(1 and 4 mg/kg) could reverse enhancement in diazepam-induced memory deficit by
melatonin. Chronic treatment with melatonin (10 mg/kg/7d) produced a similar
profile in transfer latency on elevated plus maze compared with that of diazepam.
In a food consumption behavior study, melatonin (25 and 50 mg/kg) produced a
significant hyperphagic effect compared to control. Flumazenil (4 mg/kg) could
significantly reverse the hyperphagic effects induced by diazepam (2 mg/kg), but
would be insignificant with regard to that due to melatonin. These findings
provide further evidence that some of the pharmacological effects of melatonin
are comparable with those of diazepam and may involve central GABAergic
mechanism.
PMID- 9658382
TI - Effects of gosha-jinki-gan, a kampo medicine, on peripheral tissue blood flow in
streptozotocin-induced diabetic rats.
AB - We examined the effects of Gosha-jinki-gan on peripheral tissue blood flow in
streptozotocin-induced diabetic rats and its mechanism. The decrease in peroneal
muscular blood flow in diabetic rats was dose-dependently improved by treatment
with Gosha-jinki-gan (0.1-1 g/kg/day, p.o.) for 4 weeks. Investigation of the
time course of blood flow in the hind paws revealed that single-dose of Gosha
jinki-gan (0.3, 1.5 g/kg, i.d.) increased peripheral blood flow. Peripheral blood
flow-increasing effects of Gosha-jinki-gan (1.5 g/kg, i.d.) were reduced in
combination with atropine (1 mg/kg, i.v.), and disappeared by pretreatment with
NG-nitro-L-arginine methyl ester (10 mg/kg, i.v.). Levels of aortic guanosine
3',5'-cyclic monophosphate were dose-dependently increased by administration of
Gosha-jinki-gan (0.3, 1.5 g/kg, p.o). These results suggest that Gosha-jinki-gan
has vasodilating effects via increases in nitric oxide production. Gosha-jinki
gan may be useful for treating peripheral circulation disorders in the diabetic
state.
PMID- 9658383
TI - The effect of antidepressants on rat aggressive behavior in the electric
footshock and apomorphine-induced aggressiveness paradigms.
AB - The effects of acute antidepressant treatment were studied in the electric
footshock and apomorphine-induced aggressiveness paradigms and found to be
ineffective in both experimental models. In the apomorphine-induced
aggressiveness test, 100 mg/kg L-tryptophan challenge manifested the
antiaggressive effect of 10 mg/kg fluoxetine (a selective serotonin reuptake
inhibitor) treatment. Thus, concomitant L-tryptophan plus fluoxetine treatment
decreased the intensity of aggressive postures and increased the time of latency
before first attack. In conclusion, our study demonstrates the involvement of the
serotoninergic neurotransmission in the neurobiology of aggressive behavior, but
after acute treatment in normal rats, the antidepressants do not elicit
antiaggressive effects.
PMID- 9658384
TI - Antiischemic effect of ZK-118.182 in rabbits: a comparative study with iloprost.
AB - The effects of ZK-118.182, a stable analogue of PGD2, were evaluated in an
endothelin-1-induced cerebral ischemia rabbit model. Ischemia was induced by
endothelin-1 injection (0.25 ng bolus) into subcavian artery and ischemic changes
were assessed histologically by the number of ischemic neurons in the brain stem.
ZK-118.182 (2 micrograms/kg, bolus into subclavian artery) reduced the number of
ischemic neurons when injected 20 min after endothelin-1 injection, Iloprost, a
stable analogue of PGI2, was also effective in reducing the number of ischemic
neurons in a dose of 0.5 microgram/kg (bolus into subclavian artery). The results
suggested that ZK-118.182 has a potent antiischemic effect which is comparable to
that of iloprost in rabbits.
PMID- 9658385
TI - Pharmacological activities of khellactones, compounds isolated from Peucedanum
japonicum THUNB. and Peucedanum praeruptorium DUNN.
AB - The spasmolytic and antiallergic effects of AA and BB, compounds isolated from
Peucedanum japonicum THUNB. (P. japonicum THUNB.) and Peucedanum praeruptorium
DUNN. (P. praeruptorium DUNN.), were investigated in isolated smooth muscle and
rat PCA. AA and BB showed noncompetitive antagonistic effects on Ach- and
histamine-induced contraction in the isolated guinea pig ileum. Both AA and BB at
10(-6) g/ml caused a slight shift to the right of the dose-response curve for
Ca2+ in isolated guinea pig ileum, and a concentration up to 3 x 10(-6) g/ml
displayed noncompetitive antagonistic effects. The Ba2+ (3 x 10(-4) g/ml)-induced
contraction in ileum and the histamine (10(-3) g/ml)-induced contraction in
trachea were obtained to relaxation by AA and BB in a concentration-dependent
fashion. AA and BB showed noncompetitive antagonist action on serotonin-induced
contraction of the rat uterus excised 24-48 h after subcutaneous injection of
female rats with estradiol. But, AA and BB were found to have hardly any
inhibitory effect on rabbit thoracic aorta contractions induced by epinephrine (3
x 10(-6) g/ml). When the effect of oral administration of 40 mg/kg dose of BB was
tested on the rat homologous PCA using anti-egg albumin mouse serum dilutions
(1:100, 1:250, 1:500 and 1:750), it inhibited the 1:750 serum reaction 42.6%, but
the inhibition rates for the other dilutions were 12-20%. Thus, based on the
results of testing AA and BB, compounds isolated from P. japonicum THUNB. and P.
praeruptorium DUNN. were confirmed to possess a spasmolytic effect on different
types of smooth muscle and a mild antiallergic effect. These findings are of
interest in regard to the medical uses of P. japonicum THUNB. and P.
praeruptorium DUNN. as a herbal drug for bronchial asthma, spasmolytic effect,
etc.
PMID- 9658386
TI - Prophylactic sodium valproate therapy in patients with drug-resistant migraine.
AB - We assessed the efficacy of sodium valproate as a prophylactic agent in migraine
headache. A prospective randomized study was conducted in adult patients who
previously derived no significant benefit from most conventional prophylactic
therapy for migraine. Twenty-seven patients with a diagnosis of migraine with
aura or migraine without aura from a headache clinic received low dose sodium
valproate for 3 months. Response to therapy was defined as 50% or greater
reduction in the frequency of headache. Plasma drug level monitoring helped to
identify four noncompliers who were excluded from the study. Seventeen (71%)
patients observed improvement within 4-6 weeks of medication and remained well
for 12 weeks. They were further followed up for 12-24 months. Two patients for
side effects and 1 for nondrug-related problems were withdrawn from follow-up
study. Twelve patients (60%) maintained their response for 12 months or longer.
Clinical improvement (percentage reduction in the frequency of migraine attacks)
correlated inversely with the plasma drug levels at 13-24 months and daily dose
of valproate, among the responders, suggestive of a possible therapeutic window.
In other words, patients who do not respond to low dose valproate are unlikely to
benefit from further increase in dosage.
PMID- 9658387
TI - Antigenic properties of recombinant glycosylated and nonglycosylated Pneumocystis
carinii glycoprotein A polypeptides expressed in baculovirus-infected insect
cells.
AB - Since a continuous culture system is not yet available for the opportunistic
fungal pathogen Pneumocystis carinii, obtaining suitable amounts of purified P.
carinii antigens free of mammalian-host lung contaminants is difficult. Hence,
production of recombinant antigen possessing epitopes found in native P. carinii
antigens is critical for immunological studies. We utilized the baculovirus
expression vector system (BEVS) in insect cells to determine whether B-cell
epitopes present in the protein core of a native P. carinii surface glycoprotein
were conserved in the recombinant polypeptide, and to investigate its
glycosylation by insect cells. B-cell epitopes were retained, but the insect
cells appeared to hyperglycosylate the recombinant protein.
PMID- 9658388
TI - Overproduction of soluble, extracellular cytotoxin alpha-sarcin in Escherichia
coli.
AB - The goal of the present study was to establish the condition to obtain
preparative amounts of the recombinant cytotoxin alpha-sarcin to be used for
immunoconjugate production. alpha-Sarcin cDNA was isolated from Aspergillus
giganteus strain MDH 18,894 and its expression in Escherichia coli was attempted
by the use of both two-cistron and fusion protein-expression systems. Whereas the
former resulted in low intracellular expression level of recombinant alpha-sarcin
(r-Sar), the latter allowed high-level expression of the fusion protein in the
culture supernatant. A variant form of alpha-sarcin with an additional threonine
residue in position 1 (Thr-Sar) was obtained by proteolytic processing of the
fusion protein with a final yield after purification of 40 mg/L of culture. Both
recombinant proteins r-Sar and Thr-Sar were identical to native a-sarcin with
respect to the biochemical properties and to the in vitro biological activity.
PMID- 9658389
TI - Pulsed-field gel electrophoresis.
AB - Pulsed-field gel electrophoresis (PFGE) was originally developed as a technique
for providing electrophoretic karyotypes of micro-organisms. Since then the
technique has evolved and diversified in many new directions. This review traces
the evolution of PFGE, summarizes our understanding of its theoretical basis, and
provides a comprehensive description of the methodology. Established and novel
applications are explored and the reader is provided with an extensive list of
references.
PMID- 9658390
TI - Inducible gene expression systems in Lactococcus lactis.
AB - Lactococcus lactis is industrially important microorganism used in many dairy
fermentations. Numerous genes and gene expression signals from this organism have
now been identified and characterized. Recently, several naturally occurring,
inducible gene-expression systems have also been described in L. lactis. The main
features of these systems can be exploited to design genetically engineered
expression cassettes for controlled production of various proteins and enzymes.
Novel gene-expression systems in Lactococcus have great potential for development
of industrial cultures with desirable metabolic traits for a variety of
bioprocessing applications.
PMID- 9658391
TI - Fast atom bombardment mass spectrometric characterization of peptides.
AB - Structural characterization of peptides in the range of 500-5000 Da, using fast
atom bombardment (FAB) and Cs+ ion liquid secondary ion mass spectrometry (SIMS),
is reviewed. These include synthetic peptides Kemptamide (mol wt 1516); GIF-C15
(mol wt 1875), an isolated natural product as an acylated pentapeptide; and
polypeptides generated from enzymatic digests of proteins. MS data is shown to
reveal molecular weight and sequence information as well as determine disulfide
bonds between cysteine residues and glycosylation sites in the case of a
glycopeptide. The complementarity of MS technique to classical biochemical
methods for peptide characterization is highlighted. The reader is briefly
acquainted with two newer ionization techniques namely, electrospray ionization
(ESI) and matrix-assisted laser desorption ionization (MALDI). Synthetic chemists
and biochemists can refer to the in-depth review articles that are cited
throughout this article.
PMID- 9658392
TI - A simple method for the production of highly competent cells of Agrobacterium for
transformation via electroporation.
AB - The introduction of binary plasmids into Agrobacterium hosts for Agrobacterium
mediated transformation of plants is most readily achieved by electroporation.
However, occasionally, no transformed colonies are recovered and the
transformation program is delayed. Poor transformation rates are commonly
associated with particular combinations of Agrobacterium strains and plasmid
selection markers. In order to avoid this problem, it is important for the
bacteria to have a highly competent status for reception of plasmid DNA. It is
also important to optimize the level of antibiotic for the selection of
transformed colonies. In this article, we demonstrate that transformation
competence is strongly related to the phase of growth at which a bacterial
culture is prepared for electroporation, and we describe a simple procedure that
allows the level of transformation-competent cells to be maximized. We have
observed that there is significant variation between transformed Agrobacterium
strains in the levels of antibiotic tolerance; we define the antibiotic levels
that are appropriate for selection of three Argobacterium tumefaciens (EHA101,
LBA4404, C58) and two Agrobacterium rhizogenes (LBA9402, Ar2626) strains,
transformed with three alternative resistance markers (spectinomycin(res),
kanamycin(res), and gentamycin(res)).
PMID- 9658393
TI - Antisense therapy of hepatitis B virus infection.
AB - Chronic infection with the hepatitis B virus (HBV) is a major health problem
worldwide. The only established therapy is interferon-a with an efficacy of only
30-40% in highly selected patients. The discovery of animal viruses closely
related to the HBV has contributed to active research on antiviral therapy of
chronic hepatitis B. The animal model tested and described in this article are
Peking ducks infected with the duck hepatitis B virus (DHBV). Molecular
therapeutic strategies aimed at blocking gene expression include antisense DNA.
An antisense oligodeoxynucleotide directed against the 5'-region of the preS gene
of DHBV inhibited viral replication and gene expression in vitro in primary duck
hepatocytes and in vivo in Peking ducks. These results demonstrate the potential
clinical use of antisense DNA as antiviral therapeutics.
PMID- 9658394
TI - Recovering and reamplifying of the differentially expressed cDNA bands isolated
from mRNA differential display. A modified method.
AB - Methods for retrieving and reamplifying the differentially expressed cDNA bands
have been modified. Direct reamplification of differentially expressed bands
after cutting from a polyacrylamide gel (PAG) followed by a simple rinse and
crush step has proved to be more convenient and effective than the traditional
glycogen-precipitation method. Combination of 30 cycles of differential display
(DD) polymerase chain reaction (PCR) and 20 cycles of standard PCR reaction also
yielded higher reamplification rates.
PMID- 9658395
TI - Half-embryo cocultivation technique for estimating the susceptibility of pea
(Pisum sativum L.) and lentil (Lens culinaris Medik.) cultivars to Agrobacterium
tumefaciens.
AB - Longitudinally sliced embryonic axes from pea and lentil mature seeds
cocultivated with A. tumefaciens carrying a gus reporter gene in its T-DNA
provided a convenient means to evaluate the efficiency of gene transfer to
tissues in different cultivars and cocultivation conditions. Use of this
technique demonstrated wide variation in susceptibility to Agrobacterium among
several pea and lentil commercial genotypes.
PMID- 9658396
TI - Functional role of alternative splicing in pituitary P2X2 receptor-channel
activation and desensitization.
AB - Although ATP-gated ion channel (P2XR) expression is high among anterior pituitary
cells, identification of the receptor subtypes and their selective expression
within subpopulations of cell types, as well as their physiological role(s), are
incompletely characterized. In this study, we focused on the expression and
activity of the P2X2R subtype in anterior pituitary cells. Our results indicate
that the primary P2X2R gene transcript in pituitary cells undergoes extensive
alternative splicing, with generation of six isoforms. Two of these isoforms
encode functional channels when expressed in GT1 or HEK293 cells: the wild-type
P2X2R and the spliced isoform P2X2-2R, which lacks a stretch of carboxyl-terminal
amino acids (Val370-Gln438). Four other clones showed different alterations,
including an interfered reading frame starting in the first transmembrane domain
and a 27-amino acid deletion in the large extracellular loop. When expressed
separately or in combination with wild-type channels, these clones were
nonfunctional. In single cell Ca2+ current and cytosolic Ca2+ concentration
([Ca2+)i) measurements, the P2X2R and P2X2-2R had similar EC50 values for ATP and
time courses for activation and recovery from desensitization but differed
significantly in their desensitization rates. The spliced isoform exhibited rapid
and complete desensitization, whereas the wild-type channel desensitized slowly
and incompletely. The mRNAs for wild-type and spliced channels were identified in
enriched somatotroph, but not gonadotroph or lactotroph fractions. Expression of
a functional ATP-gated channel in somatotrophs was confirmed by the ability of
ATP to increase the frequency of [Ca2+]i spikes in spontaneously active cells or
initiate spiking in quiescent cells. When voltage-gated Ca2+ influx was blocked,
ATP increased [Ca2+]i, with a similar profile and EC50 to those observed in GT1
cells heterologously expressing wild-type or spliced P2X2R. The ligand
selectivity profile of native channels was consistent with the presence of P2X2R
in somatotrophs. Finally, the desensitization rate of P2X2R in a majority of
somatotrophs was comparable to that observed in neurons coexpressing wild-type
and spliced channels. These data indicate that alternative splicing of P2X2R and
coexpression of P2X2R and P2X2-2R subunits provide effective mechanisms for
controlled cationic influx in somatotrophs.
PMID- 9658397
TI - Determination of Gab1 (Grb2-associated binder-1) interaction with insulin
receptor-signaling molecules.
AB - The newly identified insulin receptor (IR) substrate, Gab1 [growth factor
receptor bound 2 (Grb2)-associated binder-1] is rapidly phosphorylated on several
tyrosine residues by the activated IR. Phosphorylated Gab1 acts as a docking
protein for Src homology-2 (SH2) domain-containing proteins. These include the
regulatory subunit p85 of phosphatidylinositol 3-kinase and phosphotyrosine
phosphatase, SHP-2. In this report, using a modified version of the yeast two
hybrid system, we localized which Gab1 phospho-tyrosine residues are required for
its interaction with phosphatidylinositol 3-kinase and with SHP-2. Our results
demonstrate that to interact with p85 or SHP-2 SH2 domains, Gab1 must be tyrosine
phosphorylated by IR. Further, we found that Gab1 tyrosine 472 is the major site
for association with p85, while tyrosines 447 and 589 are participating in this
process. Concerning Gab1/SHP-2 interaction, only mutation of tyrosine 627
prevents binding of Gab1 to SHP-2 SH2 domains, suggesting the occurrence of a
monovalent binding event. Finally, we examined the role of Gab1 PH (Pleckstrin
homology) domain in Gab1/IR interaction and in Gab1 tyrosine phosphorylation by
IR. Using the modified two-hybrid system and in vitro experiments, we found that
the Gab1 PH domain is not important for IR/ Gab1 interaction and for Gab1
tyrosine phosphorylation. In contrast, in intact mammalian cells, Gab1 PH domain
appears to be crucial for its tyrosine phosphorylation and association with SHP-2
after insulin stimulation.
PMID- 9658398
TI - Hormone-induced proliferation and differentiation of granulosa cells: a
coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1.
AB - The proliferation and terminal differentiation of granulosa cells are critical
for normal follicular growth, ovulation, and luteinization. Therefore, the in
situ localization and hormonal regulation of cell cycle activators (cyclin D1,
D2, and D3) and cell cycle inhibitors (p27Kip1 and p21Cip1) were analyzed in
ovaries of mice and rats at defined stages of follicular growth and
differentiation. Cyclin D2 mRNA was specifically localized to granulosa cells of
growing follicles, while cyclin D1 and cyclin D3 were restricted to theca cells.
In hypophysectomized (H) rats, cyclin D2 mRNA and protein were increased in
granulosa cells by treatment with estradiol or FSH and were increased maximally
by treatment with both hormones. In serum-free cultures of rat granulosa cells,
cyclin D2 mRNA was rapidly elevated in response to FSH, forskolin, and estradiol,
indicating that estradiol as well as cAMP can act directly and independently to
increase cyclin D2 expression. The levels of p27Kip1 protein were not increased
in response to estradiol or FSH. In contrast, when ovulatory doses of human CG
(LH) were administered to hormonally primed H rats to stimulate luteinization,
cyclin D2 mRNA and protein were rapidly decreased and undetectable within 4 h,
specifically in granulosa cells of large follicles. Also in response to LH, the
expression of the cell cycle inhibitor p27Kip1 was induced between 12 and 24 h
(p21Cip1 was induced within 4 h) and remained elevated specifically in luteal
tissue. A critical role for cyclin D2 in the hormone-dependent phase of
follicular growth is illustrated by the ovarian follicles of cyclin D2-/- mice,
which do not undergo rapid growth in response to hormones, but do express markers
of FSH/LH action, cell cycle exit, and terminal differentiation. Collectively,
these data indicate that FSH and estradiol regulate granulosa cell proliferation
during the development of preovulatory follicles by increasing levels of cyclin
D2 relative to p27Kip1 and that LH terminates follicular growth by down
regulating cyclin D2 concurrent with up-regulation of p27Kip1 and p21Cip1.
PMID- 9658399
TI - Progression of LNCaP prostate tumor cells during androgen deprivation: hormone
independent growth, repression of proliferation by androgen, and role for p27Kip1
in androgen-induced cell cycle arrest.
AB - The molecular mechanism of androgen-independent growth of prostate cancer after
androgen ablation was explored in LNCaP cells. An androgen-dependent clonal
subline of the LNCaP human prostate carcinoma cell line, LNCaP 104-S, progressed
to a slow growing stage (104-R1) and then to a faster growing stage (104-R2)
during more than 2 yr of continuous culture in the absence of androgen. Androgen
induced proliferation of 104-S cells is inhibited by the antiandrogen Casodex,
while proliferation of 104-R1 and 104-R2 cells is unaffected by Casodex. This
indicates that proliferation of 104-R1 and 104-R2 cells is not supported by low
levels of androgen in the culture medium. Compared with LNCaP 104-S cells, both
104-R1 and 104-R2 cells express higher basal levels of androgen receptor (AR),
and proliferation of these two cell lines is paradoxically repressed by androgen.
After continuous passage in androgen-containing medium, 104-R1 cells reverted
back to an androgen-dependent phenotype. The mechanism of androgenic repression
of 104-R1 and 104-R2 sublines was further evaluated by examining the role of
critical regulatory factors involved in the control of cell cycle progression. At
concentrations that repressed growth, androgen transiently induced the expression
of the cyclin-dependent kinase (cdk) inhibitor p21waf1/cip1 in 104-R1 cells,
while expression of the cdk inhibitor p27Kip1 was persistently induced by
androgen in both 104-R1 and 104-R2 cells. Induced expression of murine p27Kip1 in
104-R2 cells resulted in G1 arrest. Specific immunoprecipitates of Cdk2 but not
Cdk4 from androgen-treated 104-R1 cells contained both p21waf1/cip1 and p27Kip1.
This observation was confirmed by in vitro assay of histone H1 and Rb
(retinoblastoma protein) phosphorylation by the proteins associated with the
immune complex. Furthermore, inhibition of Cdk2 activity correlated with the
accumulation of p27Kip1 and not p21waf1/cip1. From these results we conclude that
androgenic repression of LNCaP 104-R1 and 104-R2 cell proliferation is due to the
induction of p27Kip1, which in turn inhibits Cdk2, a factor critical for cell
cycle progression and proliferation.
PMID- 9658400
TI - Pituitary corticotroph SOCS-3: novel intracellular regulation of leukemia
inhibitory factor-mediated proopiomelanocortin gene expression and
adrenocorticotropin secretion.
AB - As pituitary leukemia-inhibitory factor (LIF) mediates neuroimmune signals to the
hypothalamo-pituitary-adrenal axis, we tested the role of intracellular SOCS-3 in
corticotroph function. SOCS-3, a cytokine-inducible protein of the suppressor of
cytokine signaling (SOCS) family, is expressed in the murine pituitary in vivo.
After i.p. injection of LIF (5.0 micrograms/mouse) or interleukin-1 beta (0.1
microgram/mouse) pituitary SOCS-3 mRNA was stimulated 9-fold and 6-fold,
respectively. Also, in corticotroph AtT-20 cells LIF and interleukin-1 beta both
potently stimulated SOCS-3 mRNA expression. In AtT-20 cells, stable
overexpression of SOCS-3 inhibits basal and LIF-stimulated ACTH secretion in
comparison to mock-transfected AtT-20 cells (basal: 4426 +/- 118 vs. 4973 +/- 138
pg/ml, P < 0.05; LIF-induced: 5511 +/- 172 vs. 9308 +/- 465 pg/ml, P < 0.001).
Stable overexpression of SOCS-3 cDNA in AtT-20 cells also resulted in a
significant 50% decrease of LIF-induced POMC mRNA levels (P < 0.05) and POMC
promoter activity (P < 0.001), respectively. Western blot analysis revealed an
inhibition of LIF-stimulated gp130 and STAT-3 phosphorylation in SOCS-3
overexpressing AtT-20 cells. Thus, SOCS-3 inhibits the Janus kinase (JAK) and
signal transducers and activators of transcription (STAT) pathway, which is known
to mediate LIF-stimulated ACTH secretion and POMC gene expression. In conclusion,
SOCS-3 functions as an intracellular regulator of POMC gene expression and ACTH
secretion, acting as a negative feedback mediator of the cytokine-mediated neuro
immuno-endocrine interface.
PMID- 9658401
TI - Atrial natriuretic peptide inhibits calcium-induced steroidogenic acute
regulatory protein gene transcription in adrenal glomerulosa cells.
AB - Atrial natriuretic peptide (ANP) is a potent inhibitor of mineralocorticoid
synthesis induced in adrenal glomerulosa cells by physiological agonists
activating the calcium messenger system, such as angiotensin II (Ang II) and
potassium ion (K+). While the role of calcium in mediating Ang II- and K(+)
induced aldosterone production is clearly established, the mechanisms leading to
blockade of this steroidogenic response by ANP remain obscure. We have used
bovine adrenal zona glomerulosa cells in primary culture, in which an activation
of the calcium messenger system was mimicked by a 2-h exposure to an
intracellular high-calcium clamp. The effect of ANP was studied on the following
parameters of the steroidogenic pathway: 1) pregnenolone and aldosterone
production; 2) changes in cytosolic ([Ca2+]c) and mitochondrial ([Ca2+]m) Ca2+
concentrations, as assessed with targeted recombinant aequorin; 3) cholesterol
content in outer mitochondrial membranes (OM), contact sites (CS), and inner
membranes (IM); 4) steroidogenic acute regulatory (StAR) protein import into
mitochondria by Western blot analysis; 5) StAR protein synthesis, as determined
by [35S]methionine incorporation, immunoprecipitation, and SDS-PAGE; 6) StAR mRNA
levels by Northern blot analysis with a StAR cDNA; 7) StAR gene transcription by
nuclear run-on analysis. While clamping Ca2+ at 950 nM raised pregnenolone output
3.5-fold and aldosterone output 3-fold, ANP prevented these responses with an
IC50 of 1 nM and a maximal effect of 90% inhibition at 10 nM. In contrast, ANP
did not affect the [Ca2+]c or [Ca2+]m changes occurring under Ca2+ clamp or Ang
II stimulation in glomerulosa cells. The accumulation of cholesterol content in
CS (139.7 +/- 10.7% of control) observed under high-Ca2+ clamp was prevented by
10 nM ANP (92.4 +/- 4% of control). Similarly, while Ca2+ induced a marked
accumulation of StAR protein in mitochondria of glomerulosa cells to 218 +/- 44%
(n = 3) of controls, the presence of ANP led to a blockade of StAR protein
mitochondrial import (113.3 +/- 15.0%). This effect was due to a complete
suppression of the increased [35S]methionine incorporation into StAR protein that
occurred under Ca2+ clamp (94.5 +/- 12.8% vs. 167.5 +/- 17.3%, n = 3).
Furthermore, while the high-Ca2+ clamp significantly increased StAR mRNA levels
to 188.5 +/- 8.4 of controls (n = 4), ANP completely prevented this response.
Nuclear run-on analysis showed that increases in intracellular Ca2+ resulted in
transcriptional induction of the StAR gene and that ANP inhibited this process.
These results demonstrate that Ca2+ exerts a transcriptional control on StAR
protein expression and that ANP appears to elicit its inhibitory effect on
aldosterone biosynthesis by acting as a negative physiological regulator of StAR
gene expression.
PMID- 9658402
TI - FRA-1 expression level modulates regulation of activator protein-1 activity by
estradiol in breast cancer cells.
AB - We compared the effect of estradiol on activator protein-1 (AP-1) activity in
estrogen receptor positive (ER alpha+) and estrogen receptor negative (ER alpha-)
human breast cancer cell lines transiently transfected with the AP-1-responsive
reporter plasmid AP-1-TK-CAT and an ER alpha expression vector. While estradiol
increased AP-1 activity in the ER alpha+ cell lines MCF7, ZR75.1, and T47D, it
decreased (MDA-MB231 and BT20 cells) or had no significant effect (MDA-MB435
cells) on AP-1-mediated transcription in ER alpha- cells. Estradiol also
inhibited AP-1 activity in ER alpha-MDA-MB231 cells stably transfected with ER
alpha and in which ER alpha levels are close to those found in MCF7. Use of ER
alpha mutant expression vectors demonstrated that the DNA-binding domain of ER
alpha was needed for stimulation or inhibition of AP-1 activity by estradiol but
suggested that ER alpha binding to estrogen-responsive elements was not required
for these effects. Changes in regulation paralleled quantitative and qualitative
changes in protein binding to AP-1 sites, as demonstrated by gel shift assay:
protein binding was greater and DNA/protein complexes migrated faster for ER
alpha--than for ER alpha+ cells. In fact, by Northern blot, a high level of Fra-1
mRNA was found in BT20 and MDA-MB231 cells as compared with ER alpha+ cells, and
MDA-MB435 cells showed an intermediary level of expression. The differential
expression of Fra-1 in MCF7 and MDA-MB231 cells was confirmed at the protein
level by supershift experiments. In addition, overexpression of Fra-1 in MCF7
cells decreased the positive effect of estradiol while inhibition of Fra-1
expression in MDA-MB231 cells, by transient transfection of the Fra-1 antisense
expression vector, abolished the negative effect of the hormone. In conclusion,
we demonstrated that ER alpha- breast cancer cell lines differ from ER+ cells by
a high level of AP-1 DNA-binding activity due, at least in part, to high Fra-1
constitutive expression. High Fra-1 concentration is crucial for the negative
regulation of AP-1 activity by estradiol and thus may take part in estradiol
induced inhibition of cell proliferation in ER alpha- breast cancer cells
transfected with ER alpha expression construct.
PMID- 9658403
TI - Calcium/calmodulin kinase inhibitors and immunosuppressant macrolides rapamycin
and FK506 inhibit progestin- and glucocorticosteroid receptor-mediated
transcription in human breast cancer T47D cells.
AB - The effects of immunosuppressants and inhibitors of specific calcium/calmodulin
kinase (CaMK) of types II and IV on progestin/glucocorticosteroid-induced
transcription were studied in two human stably transfected breast cancer T47D
cell lines. The lines contain the chloramphenicol acetyl transferase (CAT) gene
under control either of the mouse mammary tumor virus promoter (T47D-MMTV-CAT),
or the minimal promoter containing five glucocorticosteroid/progestin hormone
response elements [T47D-(GRE)5-CAT]. Progestin- and triamcinolone acetonide (TA)
induced CAT gene expression was inhibited in a dose-dependent manner in both
lines by preincubation with rapamycin (Rap) and, to a lesser extent, with FK506,
but not with cyclosporin A. CaMK II and/or IV inhibitors KN62 and KN93 also
inhibited progestin- and TA-stimulated transcription in both lines. None of these
drugs had any effect on basal transcription. The antagonist RU486 inhibited all
the effects of both progestin and TA, suggesting that progesterone receptor (PR)
, as well as glucocorticosteroid receptor (GR)- mediated transactivation are
targets of immunosuppressants and CaMKs in T47D cells. Indeed, Northern analysis
showed that Rap, KN62, and, to a lesser degree, FK506 inhibited progestin
stimulation of Cyclin D1 mRNA levels, but not those of the non-steroid-regulated
glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Addition of Rap or KN62
after exposure of cells to progesterone agonist Org 2058 had no effect on
induction of CAT activity. Taken together, these data indicate that Rap and
FK506, as well as CaMK inhibitors, inhibit steroid-induced activities of
exogenous, as well as of some endogenous, steroid receptor-regulated genes by a
mechanism preceding hormone-induced receptor activation. Rap appeared to
stabilize a 9S form of [3H]Org 2058-PR complexes isolated from T47D (GRE)5CAT
cell nuclei. By contrast, the progesterone receptor (PR) was isolated from cells
treated with KN62 as a 5S entity, undistinguishable from the 5S PR species
extracted from cells treated with progestin only. The nuclear 9S-[3H]Org2058-PR
resulting from cells exposed to Rap, contained, in addition to the heat shock
proteins of 90 kDa and 70 kDa (hsp90 and hsp70), the FK506-binding immunophilin
FKBP52 but not FKBP51, although the latter was part of unliganded PR
heterocomplex associated with hsp90. These results suggest that Rap and KN62 act
upon the PR by distinct mechanisms, with only Rap impeding progestin-induced PR
transformation. FKBP51 appeared to dissociate from the receptor heterocomplex,
but not from hsp90, after hormone binding to PR in vitro and in vivo, whether in
the presence or not of Rap and KN62. Immunoprecipitation experiments
distinguished two PR- and glucocorticosteroid (GR)-associated molecular chaperone
complexes, containing hsp90 and hsp70 and FKBP52 or FKBP51. Another complex
identified in T47D cytosol contained hsp90 and the cyclosporin A-binding
cyclophilin of 40 kDa, CYP40, but not hsp70, PR, or GR. These observations
support the concept that FKBP51 and FKBP52 can act as regulators of Rap and FK506
activity upon PR and GR-mediated transcription, a mechanism that could be also
regulated by type II and/or type IV CaMKs.
PMID- 9658404
TI - Serotonergic repression of mitogen-activated protein kinase control of the
calcitonin gene-related peptide enhancer.
AB - We have investigated the mechanisms underlying regulation of the calcitonin gene
related peptide (CGRP) cell-specific enhancer. Recently, we reported that this
enhancer is inhibited by serotonin type-1 (5-HT1) agonists, similar to currently
used antimigraine drugs. We have now tested whether this repression involves a
mitogen-activated protein (MAP) kinase pathway. We first demonstrate that the
CGRP enhancer is strongly (10-fold) activated by a constitutively active MAP
kinase kinase (MEK1), yielding reporter activities 100-fold above the
enhancerless control. The involvement of a MAP kinase pathway was confirmed by
down-regulation of reporter activity upon cotransfection of a dominant negative
Ras. Activation of the enhancer by MEK1 was blocked in a dose-dependent manner by
the 5-HT1 receptor agonist CGS 12066A (CGS). Since it is not known whether the
CGRP enhancer factors are immediate targets of MAP kinases, we then used EIk-1-
and c-Jun-dependent reporter genes that are directly activated by the ERK
(extracellular signal-regulated kinases) and JNK (c-Jun N-terminal kinase) MAP
kinases. CGS treatment repressed the activation of both of these reporters,
suggesting that at least two MAP kinases are the immediate targets of CGS
mediated repression. We further demonstrate that 5-HT1 agonists inactivate ERK by
dephosphorylation, even in the presence of constitutively activated MEK1. This
inactivation appears to be due to a marked increase in the level of MAP kinase
phosphatase-1. These results have defined a novel and general mechanism by which
5-HT1 receptor agonists can repress MAP kinase activation of target genes, such
as CGRP.
PMID- 9658405
TI - The murine Dax-1 promoter is stimulated by SF-1 (steroidogenic factor-1) and
inhibited by COUP-TF (chicken ovalbumin upstream promoter-transcription factor)
via a composite nuclear receptor-regulatory element.
AB - The Dax-1 gene encodes a protein that is structurally related to members of the
orphan nuclear receptor superfamily. Dax-1 is coexpressed with another orphan
nuclear receptor, steroidogenic factor-1 (SF-1), in the adrenal, gonads,
hypothalamus, and pituitary gland. Mutations in Dax-1 cause adrenal hypoplasia
congenita, a disorder that is characterized by adrenal insufficiency and
hypogonadotropic hypogonadism. These developmental and endocrine abnormalities
are similar to those caused by disruption of the murine Ftz-F1 gene (which
encodes SF-1), suggesting that these nuclear receptors act along the same
developmental cascade. Cloning of the murine Dax-1 gene revealed a candidate SF-1
binding site in the Dax-1 promoter. In transient expression assays in SF-1
deficient JEG-3 cells, SF-1 stimulated expression of the Dax-1 promoter. However,
deletion or mutation of the consensus SF-1-binding site did not eliminate SF-1
stimulation. Further analyses revealed the presence of a cryptic SF-1 site that
creates an imperfect direct repeat of the SF-1 element. When linked to the
minimal thymidine kinase promoter, each of the isolated SF-1 sites was sufficient
to mediate transcriptional regulation by SF-1. Mutation of both SF-1 sites
eliminated SF-1 binding and stimulation of the Dax-1 promoter. Unexpectedly,
mutation of either half of the composite SF-1 sites increased basal activity in
JEG-3 cells, suggesting interaction of a repressor protein. Gel shift analyses of
the composite response element revealed an additional complex that was not
supershifted by SF-1 antibodies. This complex was eliminated by mutation of
either half-site, and it was supershifted by antibodies against chicken ovalbumin
upstream promoter-transcription factor (COUP-TF). We propose that Dax-1 is
stimulated by SF-1, and that SF-1 and COUP-TF provide antagonistic pathways that
converge upon a common regulatory site.
PMID- 9658406
TI - Dominant negative regulation by c-Jun of transcription of the uncoupling protein
1 gene through a proximal cAMP-regulatory element: a mechanism for repressing
basal and norepinephrine-induced expression of the gene before brown adipocyte
differentiation.
AB - The brown fat uncoupling protein-1 (ucp-1) gene is regulated by the sympathetic
nervous system, and its transcription is stimulated by norepinephrine, mainly
through cAMP-mediated pathways. Overexpression of the catalytic subunit of
protein kinase A stimulated a chloramphenicol acetyltransferase expression vector
driven by the 4.5-kb 5'-region of the rat ucp-1 gene. Mutant deletion analysis
indicated the presence of the main cAMP-regulatory element (CRE) in the proximal
region between -141 and -54. This region contains an element at -139/-122 able to
confer enhancer and protein kinase A (PKA)-dependent activity to the basal
thymidine kinase promoter. The potency of this element was much higher in
differentiated than in nondifferentiated brown adipocytes. Gel shift analyses
indicated that a complex array of proteins from brown fat nuclei bind to the
139/-122 element, among which CRE-binding protein (CREB) and Jun proteins were
identified. In transfected brown adipocytes, c-Jun was a negative regulator of
basal and PKA-induced transcription from the ucp-1 promoter acting through this
proximal CRE region. A double-point mutation in the -139/-122 element abolished
both PKA- and c-Jun-dependent regulation through this site, and overexpression of
CREB blocked c-Jun repression. Thus, an opposite action of these two
transcription factors on the -139/-122 CRE is proposed. c-Jun content in brown
adipocytes differentiating in culture correlated negatively with both ucp-1 gene
expression and the acquisition of the brown adipocyte morphology. These findings
indicate that c-Jun provides a molecular mechanism to repress the basal and cAMP
mediated expression of the ucp-1 gene before the differentiation of the brown
adipocyte.
PMID- 9658407
TI - Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that
is related to AIB1, p/CIP, and TIF2.
AB - Nuclear receptors regulate transcription by binding to specific DNA response
elements of target genes. Herein, we report the molecular cloning and
characterization of a novel Xenopus cDNA encoding a transcription coactivator
xSRC-3 by using retinoid X receptor (RXR) as a bait in the yeast two-hybrid
screening. It belongs to a growing coactivator family that includes a steroid
receptor coactivator amplified in breast cancer (AIB1), p300/ CREB-binding
protein (CBP)-interacting protein (p/ CIP), and transcriptional intermediate
factor 2 (TIF2). It also interacts with a series of nuclear receptors including
retinoic acid receptor (RAR), thyroid hormone receptor (TR), and orphan nuclear
receptors [hepatocyte nuclear receptor 4 (HNF4) and constitutive androstane
receptor (CAR)]. However, it does not interact with small heterodimer partner
(SHP), an orphan nuclear receptor known to antagonize ligand-dependent
transactivation of other nuclear receptors. In CV-1 cells, cotransfection of xSRC
3 differentially stimulates ligand-induced transactivation of RXR, TR, and RAR in
a dose-dependent manner. Interestingly, xSRC-3 is highly expressed in adult liver
and early stages of oocyte development, suggesting that studies of xSRC-3 may
lead to better understanding of the roles nuclear receptors play in oocyte
development as well as liver-specific gene expression.
PMID- 9658408
TI - Expression cloning of a novel estrogenic mouse 17 beta-hydroxysteroid
dehydrogenase/17-ketosteroid reductase (m17HSD7), previously described as a
prolactin receptor-associated protein (PRAP) in rat.
AB - 17 beta-Hydroxysteroid dehydrogenases/17-ketosteroid reductases (17HSDs) modulate
the biological activity of certain estrogens and androgens by catalyzing
reductase or dehydrogenase reactions between 17-keto- and 17 beta
hydroxysteroids. In the present study, we demonstrate expression cloning of a
novel type of 17HSD, chronologically named 17HSD type 7, from the HC11 cell line
derived from mouse mammary gland. The cloned cDNA, 1.7 kb in size, encodes a
protein of 334 amino acids with a calculated molecular mass of 37,317 Da. The
primary structure contains segments characteristic of enzymes belonging to the
short-chain dehydrogenase/reductase superfamily. Strikingly, mouse 17HSD type 7
(m17HSD7) shows 89% identity with a recently cloned rat protein called PRL
receptor-associated protein (PRAP). The function of PRAP has not yet been
demonstrated. The enzymatic characteristics of m17HSD7 and RT-PCR-cloned rat PRAP
(rPRAP) were analyzed in cultured HEK-293 cells, where both of the enzymes
efficiently catalyzed conversion of estrone (E1) to estradiol (E2). With other
substrates tested no detectable 17HSD or 20 alpha-hydroxysteroid dehydrogenase
activities were found. Kinetic parameters for m17HSD7 further indicate that E1 is
a preferred substrate for this enzyme. Relative catalytic efficiencies (Vmax/K(m)
values) for E1 and E2 are 244 and 48, respectively. As it is the case with rPRAP,
m17HSD7 is most abundantly expressed in the ovaries of pregnant animals. Further
studies show that the rat enzyme is primarily expressed in the middle and second
half of pregnancy, in parallel with E2 secretion from the corpus luteum. The mRNA
for m17HSD7 is also apparent in the placenta, and a slight signal for m17HSD7 is
found in the ovaries of adult nonpregnant mice, in the mammary gland, liver,
kidney, and testis. Altogether, because of their similar primary structures,
enzymatic characteristics, and the tissue distribution of m17HSD7 and rPRAP, we
suggest that rPRAP is rat 17HSD type 7. Furthermore, the results indicate that
17HSD7 is an enzyme of E2 biosynthesis, which is predominantly expressed in the
corpus luteum of the pregnant animal.
PMID- 9658409
TI - Truncated SNAP-25 (1-197), like botulinum neurotoxin A, can inhibit insulin
secretion from HIT-T15 insulinoma cells.
AB - We and others have previously shown that insulin-secreting cells of the pancreas
express high levels of SNAP-25 (synaptosomal-associated protein of 25 kDa), a 206
amino acid t-SNARE (target soluble N-ethylmaleimide-sensitive factor attachment
protein receptors) implicated in synaptic vesicle exocytosis. In the present
study, we show that SNAP-25 is required for insulin secretion by transient
transfection of Botulinum Neurotoxin A (BoNT/A) into insulin-secreting HIT-T15
cells. Transient expression of BoNT/A cleaved the endogenous as well as
overexpressed SNAP-25 proteins and caused significant reductions in K+ and
glucose-evoked secretion of insulin. To determine whether the inhibition of
release was due to the depletion of functional SNAP-25 or the accumulation of
proteolytic by-products, we transfected cells with SNAP-25 proteins from which
the C-terminal nine amino acids had been deleted to mimic the effects of the
toxin. This modified SNAP-25 (amino acids 1-197) remained bound to the plasma
membrane but was as effective as the toxin at inhibiting insulin secretion.
Microfluorimetry revealed that the inhibition of secretion was due neither to
changes in basal cytosolic Ca2+ levels nor in Ca2+ influx evoked by K(+)-mediated
plasma membrane depolarization. Electron microscopy revealed that cells
transfected with either BoNT/A or truncated SNAP-25 contained significantly
higher numbers of insulin granules, many of which clustered close to the plasma
membrane. Together, these results demonstrate that functional SNAP-25 proteins
are required for insulin secretion and suggest that the inhibitory action of
BoNT/A toxin on insulin secretion is in part caused by the production of the
plasma membrane-bound cleavage product, which itself interferes with insulin
granule docking and fusion.
PMID- 9658411
TI - Dyslexia, neurolinguistic ability, and anatomical variation of the planum
temporale.
AB - This article addresses the relationship between patterns of planum temporale
symmetry/asymmetry and dyslexia and neurolinguistic abilities. Considerable
research indicates that dyslexic individuals typically do not display the
predominant pattern of leftward planum temporale asymmetry. Variable findings on
the structural basis of symmetry are due partially to measurement issues, which
are examined in some detail in this critical review. The physiological basis of
symmetry may be reduced neuronal elimination in the right planum, although other
alternatives are offered. Theories are offered to explain how symmetrical plana
are related to dyslexia, and it is evident that symmetrical plana are not
sufficient to produce dyslexia. However, some evidence suggests that nonleftward
plana asymmetry is associated with deficits in verbal comprehension, phonological
decoding, and expressive language. It is concluded that nonleftward asymmetry is
associated with linguistic deficits, but that explanatory theories need to be
further developed. Among the many issues that need to be addressed, future
research needs to determine whether the relationship between patterns of planum
temporale symmetry/asymmetry and linguistic ability is specific to dyslexia or if
asymmetry covaries lawfully with linguistic abilities in nondyslexic populations.
PMID- 9658410
TI - Neuropsychological aspects of multiple sclerosis.
AB - Since S. Rao's ["Neuropsychology of Multiple Sclerosis: A Critical Review," A
Journal of Clinical and Experimental Neuropsychology, Vol. 85, pp. 503-542]
(1986) seminal review, considerable research has been undertaken on the
neuropsychological consequences of multiple sclerosis. This review incorporates
the research literature of the last decade in presenting an overview of the
current state of our knowledge concerning the etiology, course, symptoms,
assessment, consequences, and treatment of multiple sclerosis (MS). The concept
of subcortical dementia is revisited in light of the most recent literature
documenting the neuropsychological deficits in patients with MS. The view that
cognitively heterogeneous patient groups may disguise more specific patterns of
focal neuropsychological impairment is considered. A critical review of the
recent literature is also presented, detailing the degree to which recent
research has addressed the areas of research need identified by Rao in 1986.
Given recent advances in our knowledge, the need for more attention to be
directed toward the evaluation of rehabilitation and psychological intervention
is highlighted.
PMID- 9658413
TI - [Immediate and late arrhythmia in patients operated on for tetralogy of Fallot].
AB - Arrhythmias are a frequent complication after repair of tetralogy of Fallot
(TOF). We present our experience with 97 patients with special consideration for
early and late hyperkynetic arrhythmias. The most frequent, 4% of the patients,
was in junctional tachycardia. Late arrhythmias can be atrial or ventricular. The
incidence of ventricular arrhythmias in the literature range from 42 to 82%. In
the Authors experience multiforme ventricular ectopy was present in 80% of the
patients, 20 years after surgery. We suggest an exercise test and averaging ECG
in all the patients. Thirty six percent of patients with supraventricular
tachycardia were symptomatic. CONCLUSION: as the incidence of arrhythmias after
correction of TOF is high, it is very important to periodically reassess these
patients. Antiarrhythmic treatment is indicated in all symptomatic patients,
especially in those with major arrhythmias (SVT, AF and VT).
PMID- 9658412
TI - Depression after mild traumatic brain injury: a review of current research.
AB - Research pertaining to the occurrence of depression and/or depression
symptomatology after a Mild Traumatic Brain Injury (MTBI) was reviewed. We found
that methodological differences such as the criteria used to assess MTBI and
depression, time that elapsed since brain injury, and control group variations
confounded comparisons across studies. Nevertheless, the studies are consistent
with at least a 35% prevalence of, and left frontal damage with depression after
MTBI, an overlap of symptoms of depression and Postconcussion Syndrome (PCS), and
indicate that depression can continue for many years following the injury. Our
conclusion is that MTBI is the triggering event for a set of pathophysiological
changes and a concomitant depressive episode in a vulnerable subset of the
population. Due to a paucity of research, it cannot be definitively concluded
that the underlying substrates of depression seen after MTBI and clinical
depression are the same. Implications for future investigations are discussed.
PMID- 9658414
TI - Early and late atrial dysrhythmias after modified Fontan operation.
AB - Occurrence of supraventricular tachycardia and sinus node dysfunction was
investigated pre- and postoperatively by serial ECG and Holter monitors in 63
consecutive patients with univentricular circulation after modified Fontan
operation (total cavopulmonary connection 39 patients, atriopulmonary connection
24 patients). Mean age at operation was 7.2 (0.1-20.3) years. Of the 63 patients,
14 (22%) had early (< 14 d) supraventricular tachycardia or sinus node
dysfunction, which was not related to the type of operation. None of 9 patients
with a preoperative mean right atrial pressure < or = 2.5 mm Hg had early
supraventricular tachycardia or sinus node dysfunction in contrast to 16/54
patients (30%) with a preoperative mean right atrial pressure > 2.5 mm Hg. 6/63
patients died during the early (< 14 d) postoperative period. In only 1 child,
death was related to a dysrhythmia (junctional ectopic tachycardia). During a
mean follow-up of 2.5 years, 15/57 long-term survivors (21%) had late
supraventricular tachycardia or sinus node dysfunction. Early supraventricular
tachycardia/sinus node dysfunction was a predictor or late atrial dysrhythmias,
as it occurred in 8 of the surviving 14 patients with early dysrhythmias in
contrast to 4 children without early atrial dysrhythmias (p < or = 0.001). After
creation of an atriopulmonary connection, 10/22 patients (45%) had late
supraventricular tachycardia/sinus node dysfunction, but only 2/35 patients (6%)
with a total cavopulmonary connection had late atrial dysrhythmias (p < 0.001).
CONCLUSIONS: Early atrial dysrhythmias after the Fontan operation were related to
preoperative hemodynamics. Early supraventricular tachycardia/sinus node
dysfunction and the atriopulmonary type of Fontan connection were significant
risk factors for late atrial dysrhythmias.
PMID- 9658415
TI - [Probioticss, prebiotics,synbiotics and eubiotics].
AB - The Author summarizes the most widely definitions of agents affecting the
intestinal ecosystem. Probiotic is a live microbial feed which beneficially
affects the intestinal microbial balance. Prebiotic is a non digestible food
which improves the growth of bacteria in the colon. Synbiotic or eubiotic is a
mixture of probiotics and prebiotics.
PMID- 9658416
TI - [Determination of brain death in Intensive Pediatric Therapy].
AB - The subject of this paper is to report our experience in the determination of
brain death in infants and children. We have retrospectively examined the
incidence of brain death occurred in 504 consecutive children admitted to
multidisciplinary pediatric ICU at "Bambino Gesu" Hospital of Rome during the
years 1994 to 1997. According to current Italian Law, brain death was declared in
8 children (1.6%), whose primary diagnoses were: Meningitis (3 cases);
nontraumatic intracerebral hemorrhage (2 cases); medulloblastoma (1 case); brain
metastasis of neuroblastoma (1 case); SIDS (1 case). All brain death diagnoses
were made using clinical criteria and confirmatory tests. A difficult problem was
met in achieving the required Pa-CO2 values higher than 60 mmHg without unduly
lowering O2 saturation. In order to obtain easily this objective we have recently
switched the ventilator to intermittent mandatory volume ventilation at a rate of
five stroke per minute using a FiO2 of 1 before starting the apnea test. In
infants younger than one year the required cerebral circulatory arrest was
documented in the pericallosal artery by doppler ultrasonography performed
through the fonticuli cranii. The absence of cerebral blood flow was recorded for
one to five days after clinical and electroencephalographic diagnosis of brain
death, causing an unnecessary prolonged rianimative support. This also confirms
that in young infants brain death may occur without a marked increase of
intracranial pressure. Last, but not least, we believe that particular attention
must be paid to psycho-emotional conditions of parents as well as of intensivists
and nurses especially when brain death must be assessed in children.
PMID- 9658417
TI - [Incidence of ROP (Retinopathy of Prematurity) in hypoxemic neonates: case
contribution].
AB - In this retrospective study the Authors correlated the hypoxia with the severity
of retinopathy of prematurity (ROP) in a population of 683 outborn preterm
infants (bw < 2500 g and gestational age < 38 weeks). They excluded all cases
with specific pathological conditions. Among neonates with the same gestational
age the incidence of ROP was higher (p < .05) in those with hypoxia (pH < 7.25,
tcPO2 < 50 mmHg). These data suggest that hypoxia plays a role in the
pathogenesis of ROP.
PMID- 9658418
TI - [Cardiac involvement in tuberous sclerosis in the first months of life:
physiopathologic and clinical aspects of cardiac rhabdomyoma].
AB - Cardiac rhabdomyomas are frequent in association with tuberous sclerosis and they
are the first symptoms of Bourneville disease in fetal and neonatal period.
Clinical findings of cardiac rhabdomiomas are quite heterogeneous: asymptomatic,
cardiac murmur, cardiomegaly, heart failure or arrhythmias. Echocardiography can
determine site, dimensions, numbers and haemodynamic consequences of cardiac
tumours and their clinical evolution at follow-up. In this study the Authors
report clinical findings in 9 cases of cardiac rhabdomyomas in newborn infants: 3
has familiarity for tuberous sclerosis and two of these had prenatal
echocardiographic diagnosis; in the other 6 cases diagnosis was casual (1 in
fetal period). All patients with prenatal diagnosis were asymptomatic. In other
cases 1 had extrasystolic arrhythmias and five had only cardiac murmurs.
Echocardiographic follow-up (6 months to 5 years) showed regression of number and
dimension of cardiac masses in all cases. In 7 cases cardiac rhabdomiomas were
associated with tuberous sclerosis.
PMID- 9658419
TI - [Long-term effects of combined therapy in patients with beta-thalassemia major].
AB - We evaluated therapy complications in 19 beta-thalassemia major patients (mean
age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric
Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from
matched related donor; 2 out of 19 underwent splenectomy. All of them were
receiving hypertransfusion therapy and continuous chelation with DFO. In all
patients we performed physical examination, laboratory assays, cardiac and
endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and
audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was
under 15, had a slight dilatation of left ventricle and arythmia. All patients
were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an
increase in ALT-AST serum levels since at least 6 months. In 3 of them we
assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron
overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15
patients revealed low GH levels after Arginina test. 13 pre-pubescent patients
had normal results with GNRH test but lower results after FSH test. 1 pubescent
patient had gonadotropic hypophyseal deficit. 4 patients had subclinic
hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion
therapy, chelation, profilaxis of infections improved length and quality of life
in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela
and we think it needs to be treated.
PMID- 9658420
TI - [Dyspneic bronchopathy and asthma: hospital admission between 1979 and 1994].
AB - 4,618 children, hospital admitted between 1979 and 1994 for wheezy bronchitis or
asthma, have been investigated. the patients were distributed in two groups,
according to mean age of 19 months or 8 year. An increasing incidence of asthma,
an earlier onset or respiratory symptoms, more frequent hospitalisation in
children aging less than 2 years, in recent years were observed. In elder
children however, less frequent hospitalisation occurred.
PMID- 9658421
TI - [Anxiety and memory in hospitalized adolescents; effect of the projection of a
film].
AB - The purpose of our study was the evaluation of the effects of a film on the
anxiety and memory of cronically ill adolescents (n. 25) versus healthy
adolescents (n. 25). The chronic illness was: renal failure, renal
transplantation (6 months before), scoliosis and Crohn's disease. The S.T.A.I.-Y
test was administered before and after the film to evaluate the state-anxiety
before and after the vision, only the trait-anxiety was evaluated before. The
state and trait-anxiety was not abnormal, although the state anxiety was
increased in the hospitalized adolescents before the vision (mean S.T.A.I.-Y =
43.2) and was decreasing (mean S.T.A.I.-Y = 37.32) after it. This result confirms
the needs of a global paediatric health-care in order to minimise psychosocial
traumas, associated with hospitalisation. The second goal of our research was the
mood and memory correlation and the mood-congruency. We administered two memory
tests (free and guided) using a recorder and a questionnaire. Our study presents
a better free-memory in healthy subjects (16.6% vs. 5.16% in the hospitalized
adolescents) and a better guided-memory in the healthy subjects (13.7% vs. 7.08%
in the hospitalized adolescents). Our results can't confirm the mood-congruency
theory, although the study conclusion is concerning a general decreasing of
memory competence, following the repeated hospital admissions and the chronic
illness.
PMID- 9658422
TI - [Use of a Gore-Tex patch in the primary repair of congenital defects of the
anterior abdominal wall].
AB - The surgical treatments for large omphaloceles and gastroschisis have to avoid a
dangerous primary fascial closure when it's not feasible, so the pediatric
surgeon can use staged surgical procedures that achieve a gradual increase in
size of the abdominal cavity. Therefore, a staged approach is mandatory to avoid
a complicated reduction and it's the best treatment for large congenital
abdominal wall defects. Gore-Tex soft tissue is easy to handle, pliable, soft and
well tolerated, so Gore-Tex patch closure is a safe and good alternative to
staged repair in large omphaloceles and gastroschisis. The Authors report about
five newborns with large congenital abdominal wall defects, in whom primary
fascial closure could not be accomplished, so they were successfully treated by
primary repair with Gore-Tex patch. The Authors also describe the surgical
technique and they reconsider the last surgical techniques for large omphaloceles
and gastroschisis.
PMID- 9658423
TI - [Use of radionuclides in the evaluation of intestinal transit time in children
with idiopathic constipation].
AB - Colonic transit times, in patients with chronic idiopathic constipation, in the
past were estimated using radiopaque markers. Currently they are evaluated with
colonic scintigraphy, which employs 111In DTPA orally, added to the usual
children's breakfast in a 0.05 mCi dose. Anterior views of the abdomen are
obtained at 6th, 24th, 30th, 48th, 54th, 72nd hour using a gamma camera on a 128
x 128 matrix and stored on hard disk. These images are processed in successive
times, and the colon is divided in three main segments: right-, left- and recto
sigmoid-colon. Total and segmental percentage retentions are evaluated in each
interval time. 58 children (35 males and 23 females), aged 1-12 years (mean
8.13), referred for chronic idiopathic constipation at Pediatric Surgery
Department of Siena, were studied between January 1990 and September 1996. This
group was compared with a control group formed by 15 patients (9 males and 6
females) aged 3-14 years (mean 8.53). Cutoff values, obtained in this control
group, allowed us to distinguish, among the 58 children with idiopathic
constipation, 6 symptomatic patients with normal colonic transit times and 52
symptomatic patients with pathologic ones. In this last group the evaluation of
segmentary colonic transit times allowed us to identify 13 patients (25%) with
increased right colonic transit time, 19 (36.5%) with increased left colonic
transit time and 20 (38.5%) with increased recto-sigmoidal colonic transit time.
Statistical survey allowed to distinguish significantly pathological subjects
from control group ones.
PMID- 9658424
TI - [Neonatal buprenorphine withdrawal syndrome, what is the right therapy?].
AB - Buprenorphine is a new substance now widely used in detoxification of heroin
addicts. In this report we describe the case of a newborn baby who suffered from
a neonatal withdrawal syndrome characterized by a severe and prolonged course.
This syndrome was followed by marked symptoms of impaired neurological
development and by epilepsy. The ineffectiveness of methadone in relieving
withdrawal symptoms from buprenorphine and its potential dangerous effects in
this case are also outlined, whereas the efficacy of therapy with phenobarbytal
is stressed. We think that this case is noteworthy, since the widespread use of
buprenorphine among drug addicts will probably provoke an increase in the number
of cases of buprenorphine withdrawal syndrome in the next years.
PMID- 9658425
TI - [Schoenlein-Henoch purpura following Kawasaki syndrome: a predisposition to
vasculitis?].
PMID- 9658426
TI - [Urinary hydrometrocolpos by persistent urogenital sinus; prenatal diagnosis and
neonatal management].
AB - Urogenital Sinus (UGS) malformation can be ascribed to an arrest of normal
embryonic vaginal development. Neonates with UGS frequently have ambiguous
genitalia, rarely the vulva may be normal. The aim of this work is to define the
role of prenatal sonography in the diagnosis of UGS associated with hydrocolpos
and/or hydrometrocolpos. The Authors report their experience on 3 cases of UGS
without ambiguous genitalia with hydrometrocolpos, in which prenatal sonography
had shown a cystic dilatation in the pelvis. After birth the 3 neonates presented
with female genitalia and a single orifice between the labia. The pelvis
sonography showed in all the cases an hydrometrocolpos with a large vagina and a
compressed and anteriorly located bladder. Voiding cystourethrogram, genitography
and genitoscopy confirmed the presence of an UGS with urinary retention inside
the vagina and stenosis of the distal portion of the vagina itself. An early
drainage of the capacious vagina was performed in the three patients. There are
very few reports in the literature of UGS with hydrometrocolpos diagnosed in
utero. The cystic dilatation of the vagina is always misdiagnosed with a
distended bladder. In utero, infact, the bladder can not be identified being
displaced anteriorly by the vagina. The presence of a fluid-debris level inside
the cystic anechoic mass must be considered a crucial finding. Multiple echoes
are due to vaginal secretions. Prenatal ultrasound has then a definitive role in
detecting an obstructed genital tract. This allows to rapidly drain the vagina
relieving urinary tract obstruction.
PMID- 9658428
TI - [The pediatrician and multiple sclerosis].
PMID- 9658427
TI - [An unusual case of macroscopic hematuria in pediatric age].
AB - An unusual case of macroscopic hematuria in a 14 year old boy is presented. At
the time of the first hospital admission, no urinary tract infection could be
demonstrated, in spite of the associated symptoms of stranguria and dysuria. At
ultrasound examination, only a mild thickening of the upper bladder wall was
detected, and cystoscopy showed a huge oedema and inflammation of the mucosal
layer. The biopsy of the bladder was characterized by a definite eosinophilic
infiltration; due to this particular hystologic pattern, the diagnosis of
eosinophilic cystitis was made. In the following months, the boy did not improve.
Recurrent hematuria occurred, and a pseudo-polypoid mass in the inner bladder
wall was detected at ultrasonography. A limited resection of the vesical dome was
performed, to remove completely the mass. The hystologic examination showed
Schistosoma Haematobium eggs in the bladder wall, with a typical granulomatous
reaction. The post-operative course was uneventful, and the child was completely
cured after Praziquantel treatment. The Authors underline the need to take into
account Schistosomiasis in cases of hematuria, particularly when this symptom
affects boys coming from countries where Bilharziasis is endemic.
PMID- 9658429
TI - Pediatric hematology and oncology at the Heinrich-Heine University Medical
School, Dusseldorf, Germany.
AB - The Heinrich-Heine University Medical Center is a large tertiary care hospital, a
major medical research facility, the largest teaching hospital of the Heinrich
Heine University Medical School, and a training facility for both nursing and
physiotherapy schools. In 1974, the Department of Pediatric Hematology and
Oncology was established as a separate department within the University's Center
of Child Health, serving a catchment area of 3 million inhabitants in the
northwest of the federal state of Northrhine-Westfalia. With approximately 85
newly diagnosed cases of malignant illness and 25 bone marrow transplantations
per annum, the department is one of the larger ones in Germany. The self
understanding of this unit reaches beyond immediate care of patients, however.
The department attempts to provide psychosocial support to families, patients,
and caregivers. Furthermore, it takes its responsibility as a teaching and
research facility quite seriously, aiming to add to our understanding of cancer
with the goal of improving the outcome of childhood cancer.
PMID- 9658430
TI - Successful multimodal therapy for kaposiform hemangioendothelioma complicated by
Kasabach-Merritt phenomenon: case report and review of the literature.
AB - We present the management challenge provided by a patient with kaposiform
hemangioendothelioma associated with Kasabach-Merritt phenomenon. A female child
presented at 14 months of age with an ecchymotic swelling of her right upper arm
and axilla. Subsequently, she developed profound thrombocytopenia and
hypofibrinogenemia (Kasabach-Merritt phenomenon). Biopsy of the lesion revealed
kaposiform hemangioendothelioma, which has been reported as the predominant
pathologic diagnosis associated with Kasabach-Merritt phenomenon. To achieve
involution of the lesion and preserve function of the arm, the following
interventions were involved: embolization, systemic interferon, cyclophosphamide,
epsilon aminocaproic acid, and compression therapy. The clinical management of
this patient was formidable until we arrived at the proper combination of
therapies. Multimodal intervention may be required to manage fastidious
hemangioendotheliomas of childhood, achieve clinical improvement, and prevent
further morbidity.
PMID- 9658431
TI - Aseptic osteonecrosis in children with acute lymphoblastic leukemia.
AB - Joint destruction caused by aseptic osteonecroses (AONs) is a severe complication
in acute lymphoblastic leukemia (ALL). Here, factors were determined that
influence the occurrence and clinical course of AON in ALL patients. Clinical
data of 121 patients were correlated with the occurrence of AON. Magnetic
resonance imaging was performed in patients with bone pain. Areas of AONs were
correlated with the clinical course of AON. Ten patients presented with clinical
symptoms of AON and 9 of 10 patients were graded as high-risk ALL compared with
46 of 111 patients without AON (chi 2, P < .05). In 10 ALL patients 66 AONs were
identified by MRI. In some patients up to 14 different AON sites were observed.
The courses of AONs varied in individual patients, suggesting that necrosis
specific factors might be responsible. A size above 900 mm2 was significantly
associated with progressive AON (P < .01). The more intensive treatment regimen
in high-risk ALL patients might contribute to the development of AON. The
clinical course of AON, however, is determined by necrosis-specific factors such
as a large size. These data could help in developing therapeutic strategies for
the prevention of progressive AON.
PMID- 9658432
TI - Impact of high-dose cytosine arabinoside in poor-prognosis acute lymphoblastic
leukemia: Cancer Institute experience, Chennai, India.
AB - High-dose cytosine arabinoside (HD-AraC) has been used in relapsed and refractory
cases of acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL).
Sixty-two poor-prognosis ALL patients were treated with HD-AraC between 1983 and
1995 at the Cancer Institute, Chennai, India. Of them, 37 had experienced a
relapse, 16 were partial responders (refractory) to the induction regimen, and 9
were high risk due to central nervous system or testicular involvement or total
counts above 200,000/mm3 at presentation. Of the 37 patients with relapses, 22
(59.5%) achieved complete remission (CR) and 10 had no evidence of disease (NED);
of the 16 refractory group patients, 10 achieved CR and 2 had NED; and of the 9
high-risk patients, 5 had NED at the end of the study. The 5-year event-free
survival (EFS) values of relapsed, refractory and high-risk group categories were
21.7%, 12.5%, and 55.6%, with a mean duration of 41 months, 18 months, and 85
months, respectively. Total alopecia and grade IV myelosuppression were the
predominant toxicities. HD-AraC is an effective drug in the treatment of relapsed
and refractory acute leukemias and can overcome relative drug resistance in high
concentrations.
PMID- 9658433
TI - Detection of antiphospholipid antibodies in children and adolescents.
AB - The prevalence of antiphospholipid antibodies (APAs) has not yet been studied in
children and adolescents with various diseases. We assayed plasma samples of 203
children and adolescents, aged 0.1 to 21 years (median 6 years), by enzyme-linked
immunosorbent assay detecting immunoglobulin G (IgG) and IgM antibodies directed
against cardiolipin, phosphatidylserine, and phosphatidic acid. According to
their diagnosis children were divided into five groups: 10 patients with
autoimmune and autoimmune-like diseases (group I); 88 patients with infections
(group II); 20 patients with metabolic diseases (group III); 65 children with
various other diseases (group IV); 20 healthy children without physical illnes
(group V). Results were compared for statistical significance using Fisher's
exact test. APAs were found in 65 of 203 patients. In all groups of patients the
prevalence of APAs was increased compared with healthy children. The highest
prevalence of APAs was found in patients with autoimmune or autoimmune-like
diseases or infections. Thrombosis did not occur in children with increased APA
levels. In 4 of 65 patients with detectable APAs bleeding was observed. However,
three of these four children had additional coagulation abnormalities. We
conclude that in children and adolescents increased APA titers may occur in a
variety of diseases. The frequency of APA-related symptoms is low.
PMID- 9658434
TI - Pharmacokinetic analysis of vancomycin in steady state in pediatric cancer
patients.
AB - Thirty children suffering from different types of malignancies, neutropenic
fever, and suspected staphylococcal bacteremia were evaluated for the
pharmacokinetics of vancomycin in steady-state conditions and compared with eight
children suffering from proven methicillin-resistant staphylococcal infection.
All the studied population received intravenous vancomycin at 40 mg/kg daily
divided into four daily doses. The individual pharmacokinetic parameters were
calculated using a one-compartment model for two blood vancomycin samples. The
mean (+/- SD) half-time (t1/2, hours), clearance (L/h/kg), Vss (L/kg), Cmax
(microgram/mL), and Cmin (microgram/mL) were 10.5 (7.9) and 14.9 (9.1) hours;
0.11 (0.14) and 0.06 (0.06) L/h/kg; 0.62 (0.33) and 1.3 (0.6) L/kg; 28.3 (11.8)
and 22.3 (9.8) micrograms/mL; and 5.7 (6.0) and 7.4 (4.8) micrograms/mL for the
malignancy and control groups, respectively. The malignancy group had a
significantly shorter t1/2 (P = .005), higher clearance (P = .005), and lower
Cmin (P = .03) in comparison with the control group. It is suggested that the
prescription of vancomycin at 40 mg/kg daily, divided into four daily doses, is
safe and will provide a peak blood level of vancomycin sufficient to cover the
broad spectrum of staphylococcal bacteria. The vancomycin dose should be
individualized, based on an individual pharmacokinetic profile.
PMID- 9658435
TI - Effects of intra-articular vitamin E and corticosteroid injection in experimental
hemarthrosis in rabbits.
AB - The effects of intra-articular injections of vitamin E and corticosteroid were
investigated in skeletally mature New Zealand white rabbits in which experimental
hemarthrosis was induced for 14 days. The rabbits were divided into three groups
composed of eight rabbits each: the first group comprised of animals with
hemarthrosis, the second group animals with hemarthrosis and intra-articular
injections of 20 mg vitamin E, and the third group animals with hemarthrosis and
intra-articular injections of 10 mg of triamcinolone acetonide (TCA).
Proteoglycan levels in the joint cartilage of the hemarthrosis group were found
to be increased significantly compared with the controls (P < .01), whereas in
the vitamin E-injected group they were significantly decreased (P < .05). In the
TCA-injected group, proteoglycan levels were not found to be significantly
different from those in the hemarthrosis group (P > .05). Histopathological
evaluation showed that the cartilage structure in the joint of the control limbs
was identical to that in the vitamin E- and TCA-injected limbs. In the
hemarthrosis group, in comparison with the controls, the joint surface was
roughened and fibrillated. In the superficial areas of the cartilage tissue,
chondrocytes were decreased in number. These findings suggest that in this model,
vitamin E and TCA may be helpful in preventing the joint cartilage changes seen
in hemarthrosis.
PMID- 9658436
TI - Epstein-Barr virus-associated lymphoproliferative disorder after unrelated bone
marrow transplantation in a young child with Wiskott-Aldrich syndrome.
AB - We report a case of a 16-month-old Wiskott-Aldrich syndrome (WAS) patient with a
WASP gene mutation who received human leukocyte antigen (HLA)-matched, unrelated
allogeneic bone marrow transplantation (BMT) followed by an Epstein-Barr virus
associated lymphoproliferative disorder (EB-LPD), diagnosed by clinical findings,
polymerase chain reaction detection of the EB virus genome, and spontaneous
lymphocyte proliferation of donor cell origin. EB-LPD is one of frequent lethal
complications in HLA-mismatched or unrelated BMT in this syndrome. Adoptive
immunotherapy with donor leukocyte transfusion, including appropriate numbers of
CD3-positive T cells, was effective for the EB-LPD, achieving almost complete
recovery 1 year later without any findings of graft-versus-host disease.
PMID- 9658437
TI - Evans' syndrome in a child with diabetes mellitus.
AB - A patient suffering from infantile-onset insulin-dependent diabetes mellitus is
reported in whom immune pancytopenia (Evans' syndrome) developed at the age of 2
1/2 years. Hepatosplenomegaly, chronic lymphadenopathy, and elevated levels of
immunoglobulins G and M were also present. The course of Evans' syndrome was
fatal in this patient. The association of Evans' syndrome with other immune
disorders is discussed.
PMID- 9658438
TI - Analysis of thrombopoietin and c-mpl expression in a child with essential
thrombocythemia.
AB - The pathogenesis of the increased number of megakaryocytes and thrombocytosis in
essential thrombocythemia (ET) is still unknown. We examined the expression of c
mpl, a receptor of thrombopoietin (TPO), and its signaling molecules in a patient
with ET. An 8-year-old girl showed a high platelet count and an increased number
of bone marrow megakaryocytes. Neither chromosomal abnormalities nor
myelofibrosis was observed. Following the diagnosis of ET, aspirin therapy was
begun for the patient, with only modest improvement of symptoms. Her platelet
count ranged from 1,200,000/microL to 2,200,000/microL for more than 2 years. In
the analyses, the serum TPO level in the patient was 420 attomoles/mL (normal,
760 +/- 320). The level of c-mpl expression in bone marrow mononuclear cells was
higher in the patient than in healthy children, while there was no difference in
the level of c-mpl expression in CD34+ cells, indicating an expanded pool of
megakaryocytic lineage cells. The level of Janus kinase 2 (Jak2) expression was
lower in the patient than in a healthy child. These findings indicate that the
signal pathway mediated by c-Mpl after binding to TPO may be impaired in ET.
Further analysis is needed to clarify the mechanism underlying the development of
thrombocytosis in ET patients.
PMID- 9658439
TI - Ocular involvement and visual sequelae in hemophagocytic lymphohistiocytosis in
association with congenital dyfsfibrinogenemia.
AB - We report a 7-year-old girl with hemophagocytic lymphohistiocytosis and an
uncommon complication of vascular retinopathy and visual sequelae. She was also
verified to be complicated with dysfibrinogenemia. The patient was treated with
etoposide, dexamethasone, and cyclosporin A. During the fifth hospital week, a
generalized tonic-clonic convulsion developed followed by deep coma. When she
regained full consciousness, she complained of a visual disturbance. The
ophthalmologic examination showed bilateral extensive retinal edema with numerous
cotton-wool spots, indicative of vaso-occlusive retinopathy. This is inconsistent
with the main finding of previous cases with ocular involvement, namely
papilledema. Severely reduced visual acuity and visual field defects remained in
both eyes even after systemic therapy. An awareness of this rare but serious
complication is important because it may be preventable by early institution of
chemotherapy. The pathogenesis of the retinopathy is also discussed.
PMID- 9658440
TI - Serum superoxide dismutase levels of beta thalassemia patients and effects of
high dosage of intravenous desferrioxamine treatment on superoxide dismutase
levels.
PMID- 9658441
TI - Glucose-6-phosphate dehydrogenase levels in the newborn.
PMID- 9658442
TI - Ethnoveterinary medicines used for ruminants in Trinidad and Tobago.
AB - Ethnoveterinary research was conducted in Trinidad and Tobago in 1995, in order
to document existing ethnoveterinary practices. This paper describes 20 medicinal
plants used to treat ruminants. The main plants used were Azadirachta indica and
Curcuma longa. Medicinal plants were used predominantly for endoparasites,
internal and external injuries and pregnancy-related conditions. A 4-stage
process was used to conduct the research and document the ethnoveterinary
practices. This documentation could provide a foundation for the further
scientific study and verification of those practices which merit such study.
PMID- 9658443
TI - Risk factors for false-positive serological reactions for bovine brucellosis in
Saone-et-Loire (France).
AB - Since 1990, unusually high rates of false-positive serological reactions (FPSR)
in bovine brucellosis screening have been observed in some countries of the
European Union. The aim of this survey was to describe this phenomenon in a
highly affected French Department, and to evaluate the links between some
individual or herd factors and the occurrence of these FPSR. Before 1990, low
backgrounds of FPSR were recorded (individual prevalence rate: less than 0.5 per
10,000). The phenomenon burst during the 1990-91 screening campaign, reached a
peak in 1992-93 (50.5 per 10,000), and then decreased until the last studied
campaign, 1995-96 (9.1 per 10,000). The phenomenon was transient and sporadic
within a herd. At the herd-screening level, four assumed risk factors were
isolated: (i) the probability of a herd-screening to be positive was closely and
positively linked with the herd screening size; (ii) during a given screening
campaign, the prevalence of FPSR decreased from December to November; (iii) the
presence of at least one goat on the premises increased the risk for the 1992-93
and 1993-94 screening campaigns; and (iv) a previous FPSR in a given herd
appeared to be a weak but significant risk factor. At the individual-animal
level, herd size, sex and breed did not seem to be linked with FPSR appearance,
while young animals were significantly more affected than older ones. However,
global variations in herd or individual prevalences remained unexplained. The
lack of link between FPSR and brucellosis is strengthened. The hypothesis of a
widely spread causal agent with a low individual host susceptibility and/or a low
probability of detecting FPSR animals can be supported by these results.
PMID- 9658444
TI - A Reed-Frost model of the spread of tuberculosis within seven Swedish extensive
farmed fallow deer herds.
AB - The within-herd transmission of tuberculosis, after introduction of infection,
was evaluated in seven Swedish herds of farmed fallow deer. The evaluation was
based on a subset of data obtained from a previous epidemiological investigation,
comprising 13 tuberculosis-infected deer herds, with the purpose of tracing the
source of infection. A computer spreadsheet model based on the Reed-Frost method
was developed to estimate the number of new infections. For each herd, a k-value
(the number of effective contacts made by an individual during a time period) was
estimated through fitting the model to the observed incidence in each herd. We
concluded that, despite the relatively short observation periods and uncertain
tuberculosis incidence estimates for the observed herds, the k's obtained could
be used to quantify the estimated spread of tuberculosis in extensive deer herds
in Sweden.
PMID- 9658445
TI - An epidemiological study of calcium metabolism in non-paretic postparturient
Holstein cows.
AB - Data from 1021 lactations of non-paretic Holstein cows followed in 14 Quebec
dairy herds were used to describe calcium 'metabolism' after calving in healthy
cows. Serum total calcium, phosphorus, magnesium, potassium, albumin, and glucose
were measured on the first and seventh days post-calving. The distributions were
described and compared between the first and seventh day postpartum. The
relationships between serum calcium on the one hand and the other serum
metabolites and the cow's age on the other hand were assessed using a general
linear model. Serum calcium and phosphorus values were lower on the first day
postpartum than a week later (2.03 +/- 0.26 vs 2.26 +/- 0.18 mmol/l, 1.78 +/-
0.48 vs 1.93 +/- 0.39 mmol/l, respectively), whereas it was the opposite for
glucose, magnesium, and potassium (3.98 +/- 0.95 vs 3.12 +/- 0.60 mmol/l, 1.01 +/
0.35 vs 0.95 +/- 0.13 mmol/l, 4.84 +/- 0.40 vs 4.69 +/- 0.38 mmol/l,
respectively). Albumin values were similar (25.7 +/- 3.3 vs 25.2 +/- 3.4 g/l). On
the first day postpartum, serum calcium was associated in a curvilinear fashion
with age, phosphorus and albumin. It also was associated, but to a lesser extent,
with glucose and magnesium, whereas it was not associated with potassium. On the
seventh day postpartum, calcium was associated with age, phosphorus and with an
increased importance of albumin. The results are discussed with regard to
postpartum hypocalcemia, the interpretation of serum metabolite values after
calving, and the use of the physiological stress at calving. We concluded that
(1) postpartum hypocalcemia was an event to be expected, especially for the older
cow, (2) a multivariable approach should be used to interpret biochemical
profiles after calving, and (3) such profiles could be used to better assess the
cow's health.
PMID- 9658446
TI - Ivermectin treatment did not increase slaughter weight of first-year reindeer
calves.
AB - To investigate if antiparasitic treatment of reindeer calves during the summer
could increase their carcass weight during the slaughter period in autumn and
winter, 529 reindeer calves were allocated to three groups, weighed, and marked
with individually numbered plastic ear tags in early July, 1995. One of the
groups was left untreated, another was treated with ivermectin injection at 200
micrograms/kg, and the third with pour-on ivermectin at 500 micrograms/kg.
Following slaughter, carcass weights were received from 231 animals, and there
was no difference between the treatment groups.
PMID- 9658447
TI - Risk factors for the presence of antibodies to Toxoplasma gondii in Norwegian
slaughter lambs.
AB - In a study of lambs from 194 sheep flocks from different areas of Norway, 44.3%
of the flocks were found seropositive against Toxoplasma gondii using an ELISA
test, with antibodies found in 16.2% of the 1940 individual animals. The risk
factors for the occurrence of antibodies to Toxoplasma gondii found in the
multivariate logistic regression were: daily presence of a young cat in the sheep
house (Odds ratio, OR = 4.11, 95% CI = 1.01-19.7); 'atypical' grazing of lambs
(OR = 6.35, CI = 2.36-17.11); use of mouse poison in the sheep house (OR = 2.26,
CI = 1.02-5.00); farm situated at an altitude > 100 meters above seal level (101
250 m: OR = 1.20, CI = 0.49-2.92; 251-500 m: OR = 4.97; CI = 2.04-12.0; > 500 m:
OR = 3.66, CI = 1.33-10.1). A lower risk was found for flocks with perforated
metal floors in the sheep house (OR = 0.47, CI = 0.23-0.96) and timber
construction of the sheep house (OR = 0.34, CI = 0.15-0.80). Based on these
findings it was recommended that farmers avoid keeping young cats in the sheep
houses, that close-to-farm grazing be kept to a minimum and that perforated metal
floors be used in the sheep houses. However, with such a high seroprevalence, the
proposed measures alone would not reduce the occurrence of Toxoplasma in lambs to
a level where undercooked lamb can be consumed without posing an unacceptable
risk for some consumer groups.
PMID- 9658448
TI - Theoretical and clinical aspects: an overview.
PMID- 9658449
TI - Rhythms of experience: the interplay of symmetry and asymmetry in development.
PMID- 9658450
TI - Primitive mental states: early affective processes and symmetrization.
PMID- 9658451
TI - Infinity and the limits of the unconscious.
PMID- 9658452
TI - Writing in.
PMID- 9658453
TI - Psychoanalysis, paradigm shift, and theoretical reflexivity: the case of the
Oedipus complex.
PMID- 9658454
TI - Gender configurations: relational patterns in heterosexual, lesbian, and gay male
couples.
PMID- 9658455
TI - The van Gogh family: a study in alienation.
PMID- 9658456
TI - [Role of the extracellular matrix in X-chromosome-linked muscular dystrophy:
immunohistochemical study].
AB - OBJECTIVE: To study the role of the extracellular matrix in the pathogenesis of
the X-linked muscular dystrophy. MATERIAL AND METHODS: Muscle specimens from 8
normal controls with ages ranging from 4 to 14 years of age and those of 14 X
linked muscular dystrophy patients were studied by means of polyclonal antibodies
able to recognize extracellular matrix molecules. The findings of each of the
controls and patients were evaluated systematically using a semiquantitative
morphological method. On the other hand, with the help of an automatic
interactive image analyzer, the following structures were measured: a) area
occupied by the perimysium; b) area of the endomysium, and c) transverse fibre
area. RESULTS: The deposition of the extracellular matrix components of patients
with X-linked muscular dystrophy is a selective phenomenon which is mostly
related to groups of fibers undergoing necrosis-regeneration. X-linked muscular
dystrophy patients have an heterogeneous clinical and pathological picture. At
one end of the spectrum there are patients with the most severe phenotype, in
which reduction of fiber size, early deposition of connective tissue and
distortion of the capillary bed are the most conspicuous pathological changes. At
the other end muscle fiber hypertrophy and splitting, lesser connective tissue
deposition and a milder clinical course predominate. Selective deposition of
extracellular matrix components occurs at each point of the spectrum. The
distribution of the extracellular matrix components does not appear to accomplish
a substitutive function designed to replace the loss of number or volume of the
muscle fibers.
PMID- 9658457
TI - [Gamma-sarcoglycanopathy: clinico-pathological and genetic study of 11 cases].
AB - INTRODUCTION: Limb Girdle Muscular Dystrophy type 2C (LGMD2C) is an autosomal
recessive dystrophy due to the deficit of gamma-sarcoglycan, one of the proteins
of the dystrophin-associated proteins complex (DAP). A new mutation in the gamma
sarcoglycan gene, 13q12, has been described recently and is exclusive of the
gypsy community. OBJECTIVE: To describe the clinicopathological and the genetic
findings of eleven cases from a Spanish gypsy family with LGMD2C and the mutation
C283Y. MATERIAL AND METHODS: We describe a large gypsy family with the C283Y
mutation and eleven affected patients. We have performed an extensive clinical
and pathological study with immunohistochemistry and Western blot analyses in the
eleven patients and a genetic study of a total of twenty-seven members of the
family. RESULTS: The patients presented a severe muscular dystrophy with a
dystrophic pattern in the muscle biopsy, normal immunolabeling for dystrophin,
very weak for alpha-, beta- and delta-sarcoglycan and absent for gamma
sarcoglycan. These eleven patients were found to be homozygous for the mutation
and twelve other members of the family, heterozygous. CONCLUSIONS: The clinical
picture and the evolution of the disease herein described is similar to that
observed in DMD. Two fundamental differences were found: the autosomal recessive
mode of inheritance, and the normal immunohistochemistry and immunoblot for
dystrophin in the skeletal muscle.
PMID- 9658458
TI - [3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome].
AB - INTRODUCTION: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA
lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase
catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA
and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or
coma and apnoea. Biochemically there is a characteristic absence of ketosis with
hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The
urinary organic acid profile includes elevated concentrations of 3-hydroxy-3
isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric
acids. CLINICAL CASE: Here, we report the case of a 17-year-old girl who
presented in both ten months and five years of age a clinical picture
characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia,
metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of
ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding
of hepatic steatosis and clinical and biochemical data. As of 11 years old,
laboratory investigations revealed carnitine deficiency and characteristic
aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was
made in cultured fibroblasts. CONCLUSION: Our report constitutes an example of
the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome.
PMID- 9658459
TI - [Behavioral evaluation of the unilateral lesion model in rats using 6
hydroxydopamine. Correlation between the rotations induced by D-amphetamine,
apomorphine and the manual dexterity test].
AB - INTRODUCTION: Evaluation of rotatory activity induced by dopaminergic agonists is
the most widely used test of conduct for the measurement of dopaminergic
depletion of a unilateral lesion of the striatonigral pathway caused by 6
hydroxydopamine (6-OHDA) in rats, since it is quantitatively related to the
extension of the dopaminergic denervation. OBJECTIVE: The objective of this study
was to evaluate, from different angles, the changes in conduct seen in the model
of unilateral lesion with 6-OHDA and to establish correlation with the rotation
induced by D-amphetamine and by apomorphine and the ladder test. MATERIAL AND
METHODS: Male Wistar rats were used. Lesions were produced in the SNpc by
stereotactic injection of 6-OHDA into the right hemisphere and the effectiveness
of the lesions was studied using the rotary conduct induced by D-amphetamine and
apomorphine. The motor ability of the front legs was measured by the ladder test,
carried out under standard and forced conditions. RESULTS: All the animals with
lesions had difficulty in reaching food with both legs, although the most
pronounced deficit was in the leg contralateral to the lesion. The ladder test
correlated better with rotatory activity induced by apomorphine than by D
amphetamine. CONCLUSION: The animals with most dopamine loss showed most
deficient use of their front legs.
PMID- 9658460
TI - [Frontal lobe epilepsy in infancy: is there a benign partial frontal lobe
epilepsy?].
AB - INTRODUCTION: Only the organic and cryptogenic forms of frontal lobe epilepsy
have been admitted by the ILAE, but according to several reports in the
literature, it probably exists also an idiopathic form, at present not well
recognized. OBJECTIVE: To study the differences between the organic and the
cryptogenic forms of frontal epilepsy in our patients, that might indicate the
presence of idiopathic cases within the presumed cryptogenic group. MATERIAL AND
METHODS: All patients diagnosed of frontal lobe epilepsy, EEG registered, at the
neuropediatric clinic of our hospital during 1993-1996, were selected: 30
patients under 14 years of age that were classified as organic (10 cases) or
cryptogenic (20 cases) according to CT or MRI findings. The Mann-Whitney test and
the Fisher exact test were performed for statistical analysis. Five patients with
peculiar neurocognitive symptoms, epilepsy-related, are described in detail.
RESULTS: Significative differences between the organic and cryptogenic forms of
frontal lobe epilepsy were not found except for the tendency of cryptogenic EEG
foci to spread beyond the frontal lobe, to generalize and to be associated with
foci of other localizations. Epileptic status, either convulsive or not
convulsive, were a frequent complication in both groups. CONCLUSIONS: The
identification of an idiopathic form of frontal lobe epilepsy is difficult by its
low prevalence as compared to the cryptogenic and organic forms, by the tendency
of frontal seizures to become epileptic status, which predicts an intractable
epilepsy, and by the clinical characteristics essential to frontal discharges:
heterogeneity, frequent impairment of consciousness and specially the
neurocognitive semiology, including dementia, that occurs as a critic or
paracritic phenomenon, and that sometimes may develop or be accentuated by
antiepileptic medication.
PMID- 9658461
TI - [Electroencephalogram findings in lesionectomies: preliminary results].
AB - INTRODUCTION: Use of the electrocorticogram (EcoG) in planning lesionectomies is
a controversial subject at present. MATERIAL AND METHODS: We describe a series of
5 patients with epileptic crises, 3 with arteriovenous malformations in whom the
lesion was completely resected, followed by postoperative angiography, and two
with gliomas with low grade malignancy in whom iridium 192 was implanted.
RESULTS: 1. The most frequent reason for consultation was convulsions. 2. In our
series of patients the commonest site was the frontal zone of the right
hemisphere. 3. Potentials with epileptiform characteristics were registered at
the edges of the lesions and occasionally over the lesion itself. In two cases
electro-clinical crises were seen. 4. The lesions were resected from normal
tissue independently of the EcoG results. CONCLUSION: Although they are
preliminary findings, the results of the study support the usefulness of this
technique to guide the surgical procedures used for the treatment of intractable
epilepsy.
PMID- 9658462
TI - [Blood levels of soluble ICAM-1 in patients with multiple sclerosis].
AB - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the
central nervous system. The Intercellular Adhesion Molecule plays a fundamental
part in the migration of T cells to the inflammed tissues. It is known that there
is an increase in the expression of endothelial cells and other cells found in
lesions of the central nervous system of MS patients. ICAM-I may be detected in
its soluble form in serum and it is of interest to understand its behaviour in
this liquid since it is easily accessible. MATERIAL AND METHODS: We studied the
concentration of soluble ICAM-I in the serum of patients with MS: one group which
had clinical attacks were studied whilst in remission; another had the chronic
progressive clinical form and a third group had optic neuritis as the probable
initial sign of the disorder. Within the different clinical forms, some patients
received treatment with beta-interferon or azathioprine and others did not.
RESULTS AND CONCLUSIONS: We found a significant increase in the levels of soluble
ICAM-I in patients with inactive, untreated MS as compared with normal persons,
with no difference found between the different clinical types.
PMID- 9658463
TI - [Impact of fatigue in multiple sclerosis: study of a population-based series in
Valladolid].
AB - INTRODUCTION: Fatigue is one of the commonest findings in multiple sclerosis (MS)
although it has scarcely been investigated as an independent symptom. OBJECTIVE:
To evaluate the effect of fatigue in a population based series of patients with
MS and to analyze its relation to other clinical variables. METHODS: A
descriptive, transverse study based on a geographically defined population.
Fatigue was measured using the Krupp scale in 48 patients with definite clinical
MS. We analyzed the relation between the degree of fatigue and sex, age of onset,
age at the time of the study, type of evolution, index of progression of
disability, duration of illness and degree of impairment according to the
Expanded Disability Status Scale (EDSS) and neurological functional systems.
RESULTS: 64.6% of the patients had a significant degree of fatigue. Of these, 90%
considered fatigue to be one of the three most disabling symptoms of their
illness. There was no difference between men and women in their perception of
fatigue. The patients with progressive illness, of greater age and those with
higher EDSS scores had more fatigue. This aspect was not affected by age of
onset, duration of illness nor index of progression. CONCLUSIONS: Fatigue should
be evaluated as an independent symptom of MS. Evaluation using specific scales
may contribute to better understanding of the physiopathology and investigation
of more effective treatment.
PMID- 9658464
TI - [Brain lesions of perinatal and late prenatal origin in a neuropediatric
context].
AB - INTRODUCTION: The obstetric and neonatal technological advances have changed the
frequency and syndromic classification of perinatal brain lesions. OBJECTIVE: To
study all prevalent patients during 1996, with perinatal or late intrauterine
brain lesions, in the outpatient neuropediatric clinic at our hospital. METHODS:
Selection of patients according to neuroimaging findings, and/or neurological
sequela with documented perinatal antecedent. EXCLUSION CRITERIA: a normal MRI,
brain lesions of doubtful origin, or uncertain sequela with normal CT or
echography studies. Descriptive study, and also analytical, using logistic
regression to study the relationship between antecedents and sequela. RESULTS: A
total of 111 patients with: brain lesions due to hypoxic-ischemic encephalopathy
(22 cases), lesions due to prematurity (29), late intrauterine infection or
neonatal meningitis as the only cause of fixed neurological impairment (12),
unexpected vascular brain lesions during the neonatal period (11), late
intrauterine brain lesions (37). The neurological sequela observed were: cerebral
palsy (68%), epilepsy (47%), mental retardation (45%), learning disorders in
(34%) of those of school age and free from mental retardation, strabism (26%),
microcephaly (19%), visual impairment (14%), hyperkinesis (10%). The neuroimaging
findings were: focal lesions (45%), hydrocephaly (28%), intraventricular
haemorrhage (22%), white matter lesions (24%), venous thrombosis (2%). The
multivariable analysis showed, as the most noticeable finding, the relationship
between the antecedent of mechanical ventilation and late development of
hyperkinesis (OR: 10), in this sample of patients with severe sequela. Three
patients should be noted: a case of late-onset dystonia secondary to a late
intrauterine brain lesion, a child with exclusively cerebellar symptoms due to a
destructive cerebellar lesion of prenatal onset, and a patient with an acquired
perinatal biopercular lesion and pseudobulbar palsy as the only long-term
sequelae.
PMID- 9658465
TI - [Electromyographic diagnosis of 772 patients in the Mostoles Hospital].
AB - INTRODUCTION AND OBJECTIVE: There are few references in the literature to
demographic data of the disorders most frequently studied by electromyography.
Our objective was to obtain a demographic description of the patients usually
sent to us for electromyographic studies. MATERIAL AND METHODS: Descriptive and
analytical assessment was done of 914 electromyographic diagnoses seen in a
sample of 722 patients sent to Mostoles Hospital, referral centre of Health
District VIII of the Community of Madrid with an estimated population of 407,836
inhabitants, for conventional electroneurographic and electromyographic studies
between May 1995 and February 1996. We recorded data regarding electromyographic
diagnosis, localization, intensity, whether the study was for diagnostic purposes
or follow-up, medical centre referring the patient, medical speciality sending
the patient, clinical impression, age and sex. RESULTS: The commonest pathology
seen was carpal trapping of the median nerve, both in men and in women (three
times more frequent in women). There was an estimated incidence of 136 cases per
year per 100,000 women and 36 cases per year per 100,000 men (most frequent in
patients aged 20-70, with a maximum frequency in those in their fifties). There
was marked right sided predominance. The commonest pathology in men was
polyneuropathy, with an estimated incidence of 80 cases per 100,000 men and 72
cases per 100,000 women. This was the commonest diagnosis in the patients aged
over 70. Mononeuropathy of the legs was most commonly seen in men and in the
first twenty years of life.
PMID- 9658466
TI - [Neuro-ophthalmological alternations in patients with pituitary adenomas and
intrasellar arachnoidocele].
AB - INTRODUCTION, MATERIAL AND METHODS: We studied 103 patients with hypophyseal
tumors aged between 15 and 74, with a marked predominance of females. Results. Of
these, 49 patients were diagnosed as having macroadenomas (47.5%), 27 with
microadenomas (26.2%), 25 with arachnoidoceles (24.3%) and two with
craniopharyngiomas (1.9%). Of the total there were 78.9% functioning tumors of
which the commonest was prolactinoma. CONCLUSIONS: Kinetic and static perimetry
complement each other as diagnostic methods to obtain information about damage to
the visual pathway caused by these tumors.
PMID- 9658467
TI - [Kinsbourne syndrome: review of our cases].
AB - INTRODUCTION: The childhood opsoclonus-myoclonus or Kinsbourne syndrome, is a
uncommon process, of acute or subacute beginning, which affects infant and
children. It's course is characterized by opsoclonus, polimyoclonias and
cerebellar ataxia. The disease is frequently associated to neuroblastoma (46%).
MATERIAL AND METHODS: We present a retrospective study on 9 patients, emphasizing
the clinical presentation and the evolution aspects. RESULTS AND CONCLUSIONS: We
found changes in the EEG in three cases. Most surprising is the scarce incidence
of neuroblastoma, which has been found only in a one out of nine patients. We
found three cases with relapse during the treatment or on withdrawal and one of
them relapsed twice again. The evolution has been variable, since 5/9 patient
have presented some type of mild or moderate neuro-psychological sequelae. Out of
three patient with relapses, two presented permanent neurological sequelae. A
patient which suffered three relapses, is also the one which presents more
serious sequelae.
PMID- 9658468
TI - [Characteristics of sleep in deafness].
AB - INTRODUCTION, MATERIAL AND METHODS: We studied a profoundly deaf population, in
order to evaluate the zeitgeber sleep role of the ambient sound. A closed
questionnaire was given to 36 students at a special college for the profoundly
deaf and to 321 controls of similar age and sex. RESULTS: We do not find total
upset of sleep, but a good sleep quality, probably due to the noise isolation of
the deafness. We find some traces of insecurity in falling asleep. CONCLUSION:
The ambient sound do not seem to play an important role as a sleep-wake
zeitgeber.
PMID- 9658469
TI - [Variability of the Boston test for the diagnosis of aphasia in active working
adults].
AB - INTRODUCTION: The aim of this study was to analyze the influence of age, gender,
socioeconomic status (SES), academic achievement (education), and type of
occupation, on the performance of the Boston Diagnostic Aphasia Examination
(BDAE) Spanish version. MATERIAL AND METHODS: The BDAE was administered to a
group of 156, 19 to 60 years old, occupationally active normal subjects. RESULTS:
A descriptive analysis showed that some subjects (1 to 3%) scored in the
pathological range of the centiles and profiles of the BDAE. A MANOVA (p < 0.05)
demonstrated a significant effect of education over most of the BDAE subtests.
Females outperformed males on some reading and writing subtests. SES had an
effect over body part identification and naming. Significant differences were
observed between younger and middle age groups in confrontation naming, oral and
word picture reading. The older group scored significantly lower than the younger
group in serial writing and sentences to dictation. No differences were observed
between the older and the middle groups. Only oral spelling was affected by the
type of occupation but a significant interaction of occupation and level of
education was found. CONCLUSIONS: Language tests are influenced by demographic
variables, particularly education. Normal variability on the BDAE should be
considered when dealing with clinical populations.
PMID- 9658470
TI - [Value of cranial MRI in the follow-up of dural sinus thrombosis].
AB - INTRODUCTION: At the present time it is well established that cranial magnetic
resonance (MR) is the imaging technique of choice for diagnosis of thrombosis of
the dural sinuses. However, few studies have been done to evaluate its role in
follow-up in this cerebrovascular disorder. OBJECTIVE: To assess the alterations
in resonance signal in follow-up of patients with thrombosis of the dural sinuses
and the clinical correlation of this. MATERIAL AND METHODS: We reviewed the
clinical histories of 12 patients diagnosed on cranial MR as having thrombosis of
the dural sinuses; 8 cases were also seen again six months later. The cranial MR
study was done using a 1.5 or 1.0 T superconductive apparatus to do measured spin
echo sequences (SE) in T1 and T2 in sagittal, transverse and coronal planes. The
time elapsed between diagnosis on MR and clinical diagnosis was between 24 hours
and 6 months. RESULTS: All patients had stronger resonance signals in T1 and T2
indicating a subacute phase of the thrombosis (oxidative conversion of
deoxyhaemoglobin to methoxyhaemoglobin) and complete absence of blood flow in the
sinuses. The eight patients seen again after six months were found to be normal
on neurological. On cranial MR partial recanalization was seen in 5 of these
(62%). CONCLUSION: Changes in the resonance signal persist for a long time both
with and without signs of recanalization. This finding does not affect the medium
term clinical course.
PMID- 9658471
TI - [Postural hypotension with non-neurogenic triggers in the elderly].
AB - INTRODUCTION: Orthostatic hypotension (OH) symptoms are the most frequent reason
for patients to undergo an autonomic examination. The incidence of these symptoms
is greater in two groups: young people with neurally mediated syncope, and adults
older than 60 years, all who have normal results in the EKG and EEG test. The
baroreflex afferents induce a continuous blood pressure adjustment through the
heart rate variation. There are functional changes with aging which reduce this
baroreflex sensitivity and therefore the accommodation to the haemodynamic
requirements is frequently impaired. A number of no neurogenic triggers can be
implicated in the development of OH symptoms such as electrolytic disorders,
arrhythmia with low stroke volume and drugs side effects. MATERIAL AND METHODS:
To study the influence of these factors in the elderly suffering from OH, we
reviewed patients older than 60 years sent to our laboratory during the last
three years. In 40 out of 207 cases we found the existence of some of the above
mentioned factors as possible trigger of the symptoms, since no autonomic
abnormality was present. After arrhythmia correction, in two cases, and the
pharmacologic agent suppression, in four more patients, symptoms disappeared and
no OH was found in a second tilting test. OH is a frequent problem in the elderly
and requires a careful review of the numerous causes that could contribute to
develop the symptoms. CONCLUSIONS: To take the proper therapeutic decision, a
long term monitoring seems to be necessary for the main parameters: blood
pressure and EKG.
PMID- 9658472
TI - [Rasmussen syndrome].
AB - INTRODUCTION: Rasmussen's encephalitis is a neurological disorder probably of
immunological origin, characterized by intractable epilepsy, neurological
deterioration and the presence of antibodies against R3 glutamate receptors.
OBJECTIVE: To present the experience of an Argentinian Paediatric Neurology
Service during the past 7 years. MATERIAL AND METHODS: We analyzed the clinical
histories of 12 patients with RS as defined by the diagnostic criteria proposed
by Hart et al. We evaluated the following parameters: neurological examination,
neuropsychological assessment, types of crises, age of onset, frequency,
distribution, electroencephalogram, video EEG, evoked potentials, neuro
radiological studies; CT and cerebral MR using gadolinium, SPECT, lumbar puncture
and cerebral biopsy. RESULTS: The crises were of simple partial motor type in 12
cases, secondarily generalized partial crises in 7 cases, complex partial crises
in 4 cases and partial and generalized motor states in 8 cases. RESULTS. The
ictal EEGs during the continuous partial crises showed contralateral focal slow
activity of the affected side of the body in 30% of cases. The neuro-radiological
studies (CT and MR) showed signs of cerebral hemiatrophy in all 12 cases, hyper
intense images in the T2 sequences of the fronto-temporo-parietal regions in 5
cases, an asymmetric megacisterna magna in 1 case and hypoplasia of the
cerebellar vermis in another case. CONCLUSIONS: The continuous partial crises
showed little correlation with the electro-encephalography. Following
administration of i.v. gammaglobulin there was a transient halt in progression of
the neurological deterioration and control of the crises in 55% of the cases.
Surgery continued to be the treatment recommended for control of the epileptic
crises.
PMID- 9658473
TI - [Study of the brachial plexus by magnetic resonance].
AB - OBJECTIVE: Magnetic resonance (MR) is considered to be the best method available
at present for diagnosis of lesions of the brachial plexus. In this study we
analyze our experience in patients with pathology of the brachial plexus.
MATERIAL AND METHODS: Between August 1991 and March 1997 we did magnetic
resonance studies on 42 patients with pathology of the brachial plexus. Our
protocols included T1, T2 axial spin-echo sequences with 5 mm cuts and coronal
echo of a T1-3D gradient with 2 mm cuts, together with a T1 coronal spin-echo,
with cuts 2 mm in width. RESULTS: The causes found were: traumatic 16 patients
(38%), pathology of bone 2 (4.7%), 19 tumours (45.2%) with breast cancer being
commonest, and no obvious aetiology in 5 (11.9%). CONCLUSIONS: MR is the
technique of choice for study of pathology of the brachial plexus of traumatic or
tumour origin. In some patients, 11.9% in our series, no aetiology could be
detected using MR.
PMID- 9658474
TI - [Topographic distribution of visual evoked potentials in optic neuropathy].
AB - INTRODUCTION: Digital treatment of electrical signals coming from the central
nervous system on stimulation of the optic nerve path offers an objective method
for evaluation of visual evoked potentials (VEP) shown graphically on a cerebral
map. OBJECTIVE: To evaluate the topographical distribution of VEP in cases of
optic neuropathy adding this parameter to the usual parameters of latency and
amplitude. MATERIAL AND METHODS: We studied 35 patients with suspected optic
neuropathy and normal findings on basic ophthalmological examination, in whom VEP
and VEP mapping (VEPM) was done. RESULTS: In 26% of the cases there was no
response for evaluation with the usual VEP recording techniques, whilst in those
with VEPM this percentage was reduced to 11.5%. In the other cases there was a
potential with characteristic distribution in the occipital areas and a maximally
positive dipole posteriorly. CONCLUSION: VEPM is an objective method for
evaluation of the visual pathway offering better discrimination than the usual
VEP in more severe cases of neuropathy.
PMID- 9658475
TI - [Neuroradiology, a specialty among the neurosciences].
AB - Neuroradiology as a Neuroscience speciality has to keep undoubtedly a narrow
relationship with the rest of the branches of Neurological Diagnostic, but mainly
with Clinical Neurology, Neurosurgery and Neuropathology. It is specially
remarked that cooperation with Neurosurgery has to be very narrow not only in
diagnostic field as in evaluation of Neuroradiology operation techniques
(endovascular therapy) as in the field of Stereotaxis and Radiosurgery.
PMID- 9658476
TI - [Direct communication on the Internet. Uninet: the university link for Integrate
Telematic Services].
AB - The importance of Internet as a communication medium is clear due to the amount
of information it distributes and the high number of potential recipients it has.
The appearance of virtual user communities (CMV) focuses to information
classification within subjects of interest for certain groups of people in order
to facilitate its search and use. The UniNet project of Integrated Telematic
Services for CMV through, as well as other subprojects, the 'propuesta RedUni'
encourages the creation of CMV by mean of integration of various computer and
Internet resources, such as distribution mailing list, web pages, Internet Relay
Chat (IRC), etc. The current state of IRC in such context is presented and the
utilities of the known as Scientific-IRC as a professional real time
communication tool are discussed.
PMID- 9658477
TI - [Arteriography using helicoidal computerized tomography in the study of complex
aneurysms of the circle of Willis].
AB - INTRODUCTION: Computed tomography angiography (CTA) can add information to
digital subtraction angiography (DSA) in selected cases of aneurysms of the
circle of Willis. CLINICAL CASES: 1. Patient with progressive visual loss and
headache. CT and DSA showed an image of partially thrombosed suprasellar
aneurysm. CTA better defined the relationship between the lesion and regional
vessels. 2. Woman with subarachnoid hemorrhage (SAH). CTA defined the aneurysmal
neck and its relationship to the clinoid process. 3. Man with SAH, CT and DSA
showed an arteriovenous malformation and three arterial aneurysms one of which
was in a tortuous vessel. CTA confirmed digital angiographic data. CONCLUSION:
CTA is a new image technique that can either add or confirm DSA findings in
complex aneurysms of the circle of Willis.
PMID- 9658478
TI - [Clinico-radiological dissociation in cerebral hemorrhage caused by
afibrinogenemia].
AB - INTRODUCTION: Congenital afibrinogenemia is a very rare hereditary anomaly of
coagulation. Only 150 cases have been published. Clinical manifestation in the
form of some type of bleeding is similar to that of other congenital
coagulopathies, although the pattern of presentation is different. Spontaneous
bleeding is rare, but slight injury, which may be unnoticed, may trigger it off.
In spite of being a congenital condition, it may be of late onset, as in our
patient, with bleeding episodes occurring in the second decade of life. CLINICAL
CASE: We describe a woman who had several episodes of bleeding, two of which were
intracerebral. The principal feature of this was dissociation between the
clinical findings and their detection by neuro-imaging. Substitutive therapy led
to the disappearance of symptoms. CONCLUSION: Cerebral haemorrhage in the
presence of afibrinogenemia may fail to be detected early on CT. On clinical
suspicion of bleeding, early substitutive treatment should be started.
PMID- 9658479
TI - [Progressive aphasia without dementia].
AB - INTRODUCTION: Slowly progressive aphasia without generalized dementia is
considered as a degenerative disorder that can be differentiated of others well
known neurodegenerative disorders. CLINICAL CASE: We present a case report of a
patient with slowly progressive aphasia, characterized by a progressive anomia
and without generalized dementia. The patient was evaluated in the last four
years: a neuropsychological assessment, a neurological exploration and structural
(MRI) and functional (SPECT) neuroimaging were performed. CONCLUSION: This case
is interesting on account of a selective implication of the left temporal
hemisphere is showed in the pathogenesis of this disorder.
PMID- 9658481
TI - [HIV myelopathy as the presenting symptom of acquired immunodeficiency syndrome].
AB - INTRODUCTION: Spinal lesions in the acquired immunodeficiency syndrome (AIDS)
occur in 22% of all neurological complications, although their occurrence as the
first sign of the disease is very uncommon. First place amongst the myelopathies
described as associated with HIV is taken by vacuolar myelopathy, followed by the
myelites. CLINICAL CASE: We studied a 65 year old homosexual man who had
previously been free of symptoms and signs of HIV infection. He was seen for
progressive paraparesia which had begun some days previously, followed by altered
sense of position and of vibration. Complementary tests showed that the patient
was a carrier of HIV antibodies in high titre (P-24) with a high viral load of
907 x 1,000 copies RNA/ml. Testing with evoked potentials showed changes
compatible with involvement of the sensory pathways of the spinal cord. After
treatment with dexamethasone there was obvious improvement with partial recovery
of his symptoms. CONCLUSIONS: The neurological condition described was compatible
with vacuolar type myelopathy due to HIV, appearing in the initial stages of the
illness and coinciding with a marked increase in the viraemia. Although necropsy
is necessary for confirmation of the diagnosis, more and more evidence is being
found on which to base clinical suspicion. We discuss various hypotheses
regarding possible pathogenic mechanisms arising in these circumstances.
PMID- 9658480
TI - [Central nervous system infection by free-living amebas: report of 3 Venezuelan
cases].
AB - INTRODUCTION: Infection of the Central Nervous System by free living amebas is an
unusual event, 344 cases have been reported to date. The disease becomes evident
in two different clinical fashions: Primary Amebic Meningoencephalitis (PAM)
caused by Naegleria fowleri and Granulomatous Amebic Encephalitis (GAE) induced
by Spp. of Acanthamoeba and Balamuthia. CLINICAL CASES: The authors report three
new cases from Venezuela. Case 1. 34 years old man, with a chief complaint of
general malaise, headache and fever, a diagnosis of common cold was made and the
patient was treated as such, he did not improve and was admitted to the hospital
with deterioration of his clinical status; the patient died 10 days after the
onset of his illness which was determined to be GAE produced by Balamuthia
mandrillaris. Case 2. 8 years old female admitted to the hospital because of
fever, headache and generalized seizures of sudden onset; neurocysticercosis was
diagnosed and following improvement the patient was discharged and readmitted on
two occasions because of relapse and worsening of her illness, she died 2 months
after the onset of her disease that was diagnosed by autopsy as GAE due to
Balamuthia mandrillaris. Case 3. 16 years old male, previously healthy, who
following immersion in a water tank was admitted to the hospital because of
meningeal irritation that progressed to coma and death in a 7 day lapse; autopsy
revealed PAM by Naegleria fowleri. The two cases of GAE due to Balamuthia
mandrillaris occurred in apparently immunocompetent individuals, contrary to the
statement that these microorganisms are opportunistic. CONCLUSION: We believe
that neurological infection by amphizoic amebas is being underdiagnosed, probably
due to ignorance regarding this pathology or because of a very low autopsy rate
in most countries.
PMID- 9658482
TI - [Partial complex status epilepticus: diagnostic difficulties].
AB - INTRODUCTION AND CLINICAL CASE: We present a case of complex partial non
convulsive status epilepticus which we think it is very interesting because it
caused a challenged diagnostic. The patient, a male of eleven years old had
affective symptoms in episodes. They occurred lasted six to eight hours, once or
twice a month. The seizures began after a stressfully psychology experience.
Currently and after of some months of follow-up, the patient is free of symptoms
and he receives a treatment with valproate acid and vigabatrin. CONCLUSION: We
also discuss possible precipitating factors, differential diagnosis and
prognosis.
PMID- 9658483
TI - [Familial benign partial epilepsy of early infancy].
AB - INTRODUCTION AND CLINICAL CASES: We present two patients who at the ages of 5 and
17 months respectively presented with convulsive crises with motor signs, of
partial onset and secondary generalization, which eventually became normal. Both
patients had a family history of first degree relatives with similar illnesses
and are at present-five years later-well and with normal development, school
achievement and neurological examination findings. The clinical characteristics,
normal biochemical and neuroimaging investigations and EEG characteristics
suggest the diagnosis of benign partial epilepsy of early infancy. This syndrome
is characterized by its appearance during the first year of life, having no known
etiological factors, with partial crises occurring several times a day and with a
course leading to remission. Its frequency may be greater than is thought. There
is a pattern of dominant autosomal inheritance, with a gene recently found on
chromosome 19. CONCLUSION: We consider that this syndrome should be included in
the International Classification of Epilepsy and Epileptic Syndromes as benign
familial idiopathic partial epilepsy.
PMID- 9658484
TI - [Paraneoplastic cerebellar degeneration with asymmetrical pan-cerebellar
syndrome].
AB - INTRODUCTION: Paraneoplasic cerebellar degeneration is seen clinically as a
pancerebellar condition which is usually symmetrical. Different families of
tumours are associated with this, particularly (in view of its frequency) oat
cell pulmonary carcinoma, gynecological tumours and Hodgkin's lymphoma. CLINICAL
CASE: Signs of cerebellar atrophy were seen on MR and cortical hypoperfusion was
seen on Single Photon Emission Computerized Tomography (SPECT). We present the
case of a 76 year old woman who presented with an asymmetrical pancerebellar
disorder of gradual onset, with positive anti-self antibodies and
undifferentiated carcinoma of the breast. CONCLUSIONS: Paraneoplasic cerebellar
degeneration should be suspected in a patient with symmetrical, progressive
cerebellar disease. The syndrome characteristically starts with a slightly
uncoordinated gait. This progresses over a period of weeks or months to an ataxic
gait with incoordination of the limbs, dysarthria and frequently nystagmus with
oscilloscopy. No satisfactory treatment has been found for DCP in spite of trials
with vitamins, corticosteroids, plasmapheresis and immunoglobulin infusion.
Slight improvement may be seen after treatment of the primary tumour.
PMID- 9658485
TI - [Acute phenytoin poisoning secondary to an interaction with ticlopidine].
AB - INTRODUCTION: Ticlopidine and phenytoin are two drugs which are widely used in
everyday clinical practice, the first as a platelet anti-aggregant and the second
as an anti-epileptic agent. Their association is not uncommon, since there is a
high incidence of epileptic crises of vascular origin in adults. CLINICAL CASE:
We present the case of a 77 year old man who had been treated for twenty years
with phenytoin for partial crises secondary to a left frontal hematoma. He then
followed treatment with ticlopidine for a femoropopliteal bypass, and the dose
was later increased because of a vertebro-basilar ictus. On both occasions he
presented with ataxia, dysarthria and nausea due to phenytoin intoxication. The
blood levels of this drug were above the therapeutic level. The symptoms
disappeared and the patient returned to normal after reduction of the dose of
phenytoin and suspending treatment with ticlopidine. DISCUSSION: The mechanism of
action of ticlopidine at cytochrome P450 level, inhibiting the metabolic
clearance of phenytoin, was responsible for this interaction. We have found only
three other cases of interaction between these drugs in the literature, and ours
is the first to be published in Spain. CONCLUSION: We emphasize the importance of
checking plasma phenytoin levels when starting treatment with ticlopidine, since
it may be necessary to reduce the dose of phenytoin.
PMID- 9658486
TI - [Polyneuropathy caused by vitamin B12 deficiency secondary to chronic atrophic
gastritis and giardiasis].
AB - INTRODUCTION: In chronic atrophic gastritis atrophy of the stomach glands leads
to intrinsic factor deficit, with consequent failure to absorb vitamin B12 and
gastric achylia, which predisposes to Giardia infection which in itself leads to
depletion of vitamin B12. We describe the case of a patient with peripheral and
central nervous system pathology due to lack of vitamin B12 secondary to the
combined effect of these two disorders. CLINICAL CASE: A 54 year old woman
consulted us for paraesthesia and weakness of the legs which had been progressive
for the previous two years. She presented with tactile hypoaesthesia,
hypoparaesthesia, distal hyperreflexia and dysymmetry of the legs, ataxic-spastic
gait and a positive Romberg sign. The investigations carried out showed the serum
vitamin B12 level to be 3 pg/ml (N: 180-900), hemoglobin 13 g/dl and MCV 111 fl
with MCHC 348/dl; neurophysiological studies: compatible with demyelinating motor
polyneuropathy. Schilling test: deficit of absorption of vitamin B12 which was
corrected on administration of intrinsic factor; gastroscopy; atrophic gastritis
which confirmed the morbid anatomy findings. There was also flora containing
Helicobacter and massive Giardia infection. Replacement and antibiotic therapy
was followed by complete remission of the clinical picture. CONCLUSION: We
emphasize the excellent clinical response to treatment in spite of the time
elapsed since onset of symptoms.
PMID- 9658487
TI - [Dystrophinopathies, congenital muscular dystrophy, limb-girdle dystrophies:
updated classification].
AB - OBJECTIVES: To review the up-dated classification of limb girdle muscular
dystrophies (LGMDs) in relation to the defective protein and the genetic
abnormality. To explain how these proteins are related to dystrophin and to the
proteins of the extracellular matrix. To show that an accurate diagnosis is
necessary and that it can be adequately made in neuromuscular pathology
laboratories. DEVELOPMENT: We present a study of the different types of LGMDs,
dystrophinopathies and congenital muscular dystrophy. We emphasize the recent
events which concluded in the identification of these disorders, the genetic
alteration, the defective proteins and, briefly, the clinical features.
CONCLUSIONS: The recent identification of numerous skeletal muscle proteins and
of the codifying genes made possible a new classification of a large group of
muscular dystrophies. The possibility to study these proteins on the muscle
biopsy with immunohistochemistry and Western blot techniques indicates the need
of an accurate diagnosis in specialized neuromuscular laboratories. Since there
is a great number of genes discovered and of mutations within the same gene, and
the clinical picture of different diseases can be similar, a previous study of
the protein is advisable as a guide for a further genetic study.
PMID- 9658488
TI - [Brain-derived growth factor: current aspects].
AB - INTRODUCTION: The neurotrophins are a family of proteins which are closely
related structurally and functionally and include nerve growth factor (NGF),
brain derived nerve factor (BDNF) and neurotrophin-3 (NT-3), neurotrophin-4/5 (NT
4/5) and more recently neurotrophin-6 (NT-6). BDNF is one of the most important
endogenous proteins for control of survival, growth and differentiation of
certain neurone populations both in the peripheral and central nervous systems.
DEVELOPMENT: The ARNmt of the BDNF is found in nearly all regions of the brain.
The highest levels are those of the hippocampus and cerebral cortex. The large
number of effects attributed to BDNF are probably due to the union of this
protein to its specific receptor on the cell surface, which leads to the
formation of a complex which enables transmission of the signal caused by
activation of the specific neurone pathway. Since discovery, BDNF has been
detected and/or measured by different methods from biological assay to the
application of molecular biology techniques. These methods have permitted
analysis of the biochemical characteristics of this factor and its behaviour in
different tissues. CONCLUSIONS: In this paper we review the most relevant aspects
of distribution, biological actions of BDNF on different neurone populations, its
clinical usefulness in neurological disorders, routes of administration and side
effects.
PMID- 9658489
TI - [Nerve growth factor and diabetic neuropathy].
AB - INTRODUCTION: The progress made by contemporary neurobiology opens new horizons
both for study and for treatment of disorders of the nervous system. At the
present time we are in the age of growth factors. These are molecules which
affect survival, development and the normal functioning of cell populations.
DEVELOPMENT: One of the most widely studied growth factors is nervous growth
factor (NGF) which is necessary for normal life of various types of neurones,
including sensory nerves and nerves derived from the neural crests. Diabetic
neuropathy, worldwide a major neurological disorder, is primarily characterized
by involvement of the fine fibres for temperature and pain perception and also by
a variety of autonomic disorders. The great dependence of sensory and sympathetic
nerves on NGF, the quantity of results which show alterations in the levels of
neurotrophic factors in diabetic neuropathy (DN), and the encouraging
experimental and clinical results of using NGF as a new alternative to treatment
with DN, were the basic reasons which led us to do this study. CONCLUSIONS: We
started by considering neurotrophic factors, especially NGF and its connection
with DN disorders and its clinical applications, we made a summary of the main
findings in this field to date.
PMID- 9658490
TI - [A new formulation of death: definition, criteria and diagnostic tests].
AB - OBJECTIVE: To present a new formulation of human death based on neurological
considerations. DEVELOPMENT: One of the reasons there is still controversy over a
new formulation of human death which is acceptable to society, is that many
authors do not suitably integrate three fundamental aspects which should be
included in such a formulation: definition, criteria and diagnostic tests. We
review the physiopathological mechanisms for generation of consciousness and
discuss the three fundamental criteria presented by different authors in recent
decades: the whole encephalum, brainstem death and neocortical criteria. We
conclude that there are major contradictions in the three criteria with regard to
satisfactory integration of the elements, definition, criteria and diagnostic
tests. We therefore present a new formulation of human death. DEFINITION:
irreversible loss of consciousness, since this gives the essential human
attributes, and is the most integrating function of the organism. CRITERIA:
cortico-subcortical connections for the generation of both components of
consciousness (capacity and content). DIAGNOSTIC TESTS: no waking response to
stimuli (capacity), no cognitive nor affective functions (content). CONCLUSIONS:
We present a new formulation of human death on a neurological basis which permits
satisfactory integration of the three fundamental elements, definition, criteria
and diagnostic tests, and so offers a suitable starting point from which man may
start to understand death.
PMID- 9658491
TI - [A complete and precise reformulation of human death].
AB - INTRODUCTION: Today, a very active debate exists about the concept and
determination of death. The lack of both an integrating rationale and a
consistent and precise formulation to approach such a fundamental issue has been
notable. However, a contribution regarding both aspects is indispensable to
overcome inconsistencies affecting current death concepts. DEVELOPMENT: It is
argued in this article why a sufficiently defined 'consciousness-organism-as-a
whole' system and its critical metafunction determines the neurological standard
for a complete and precise reformulation of human death. This metafunction cannot
be reduced to any of the particular functions of the system. It characterizes the
highest hierarchical level of qualitative organization in the human organism. It
defines the criticality of the system and the ontological level pertinent to the
definition of death. Human death is 'both the irreversible loss of consciousness
(considering its three anatomical and physiological components), and, inherently
and inseparably, the loss of the capacity of the organism to function as a
whole'. CONCLUSIONS: It is argued why the rationale supporting this definition
overcomes the problems posed by either currently accepted conceptions or by those
competing to gain acceptance. Some of the implications of this re-approach in the
intersection of neurology with other disciplines are considered.
PMID- 9658493
TI - ["El Informe Medico-Moral de la Penosissima y Rigorosa Enfermedad de la Epilepsi"
(1763) by the Spaniard Pedro de Horta, the 1st American treatise on epilepsy].
AB - In 1763 Pedro de Horta was requested by the prioress of the convent of San
Geronimo in Puebla de los Angeles to draw up a report to establish whether the
epidemic of queer turns, violent shaking or epilepsy which affected the novices
was caused by the Devil or was due to natural causes. Pedro de Horta, a doctor
qualified in Mexico, methodically and thoroughly prepared an extensive
monographic treatise on the illness which included all that was known at the
time. The report showed the fierce debates provoked by the subject of epilepsy in
the eighteenth century regarding whether it was of natural or supernatural
origin. It also contained detailed accounts of the episodes, their causes and
treatment. The Spaniard Pedro de Horta should be justly recognized as the first
American epileptologist.
PMID- 9658492
TI - [Medical treatment of Alzheimer's disease].
AB - OBJECTIVE: To review the drugs commercially available at present and in the near
future in relation to the evolution of Alzheimer disease, bearing in mind the
possible psychiatric disorders which may be associated with the disease.
DEVELOPMENT: The therapeutic approach is planned according to the different
phases of the disease. In the preclinical phase, anti-inflammatory drugs and
estrogens in post-menopausal women have been effective. In the initial phase
current recognition therapy is directed basically towards correcting the break
down of acetylcholine (tacrine, donepezil, SB202026, SDZ ENA 713). For depressive
symptoms serotonin levels are corrected using selective inhibitors of serotonin
uptake. CONCLUSIONS: Drug treatment should be considered with the association of
drugs which activate the malfunctioning circuits and/or pathways. It would also
be useful to design clinical studies using pharmacological combinations of
cholinergic agonists, estrogens, anti-inflammatory drugs, seligiline and/or new
anti-cholinesterase drugs amongst others.
PMID- 9658494
TI - [Magical thinking and epilepsy in traditional indigenous medicine].
AB - INTRODUCTION: Witchcraft with regard to epilepsy in ancestral indigenous cultures
has been modified by the presence of white doctors so that traditional and
scientific-western treatments coexist. OBJECTIVE: To analyze traditional anti
epileptic treatment and the basis of the relevant magic in diverse indigenous
cultures in Central Africa and in Central and South America. MATERIAL AND
METHODS: Transcultural analysis of the Bassa, Fufulve and Bambilike tribes (Log
bikoy, Camerun), Wangoni (Songea, Tanzania), Guarani (Paraguay) and Maya Tzeltal
(Chiapas). RESULTS: In traditional Africa epilepsy is linked to the evil eye. In
the Wangoni tribe the curative ritual requires complete shaving of the entire
body using glass, or banishment of the person causing the evil influence. In the
Bassa and Bambilike, burns are a common complication and epilepsy is known as the
disease of people with burns. In Meso-american culture epilepsy is caused by some
abuse suffered by the animal soul which accompanies the person involved,
following a battle between the naguales or spirits who serve the forces of Good
and Evil. Traditional indigenous medicine employs herbal remedies, rituals,
spiritual cures or combinations of all these. More than 80% of the epileptic
patients of the Third World use only these remedies. CONCLUSION: The mythical
concept of the disease is the basis for interpretation of epilepsy in traditional
indigenous cultures. The psychological benefit obtained from the traditional
therapeutic model has made this necessary and complementary to western-style
treatment.
PMID- 9658495
TI - [Quality of life of the pediatric epileptic patient].
PMID- 9658496
TI - [Acute disseminated bulbospinal encephalomyelitis in an adult patient].
PMID- 9658497
TI - [Neurocysticercosis and convulsive crises].
PMID- 9658498
TI - [The concept of "person" and its neurological foundations].
PMID- 9658499
TI - [Neurology and the concept of health].
PMID- 9658500
TI - [William G. Lennox and the International League against Epilepsy: sketch of a
life and an opus].
PMID- 9658501
TI - [Guillain-Barre and varicella infection].
PMID- 9658502
TI - [Transitory comatose situation secondary to an infarction of the posterior
circulation, reversed by naloxone?].
PMID- 9658503
TI - [Prevalence of amyotrophic lateral sclerosis on the island of La Palma, Spain].
PMID- 9658504
TI - Health promotion in school age children.
AB - Disadvantage in school age affects health during the remaining part of life.
Health promotion might alleviate this situation. It is reasonable to focus on
mental health, since this is the leading cause of disability adjusted life years
lost in this age group and to focus on the school, since this is the most
important setting. Co-operation between the public health and the educational
sector is rational, yet complicated by different perspectives on knowledge and
technology used in these two sectors. It is, however, possible to carry through a
dialogue. Then, the public health representatives have to clarify current
scientific knowledge on health promotive characteristics of the school. Such
characteristics are, enhanced health control at school, aged mixed ability
grouping, class sizes of 15-20 students, a task oriented school culture and
employment of skills training programmes, e.g. for tobacco deterrence.
PMID- 9658505
TI - Rehabilitation research under fire.
AB - Catastrophes in the health area are frequent. A template for conduct and
reporting of research in disaster responses has recently been published. The WHO
Rehabilitation of War Victims Project basically followed these principles in
former Yugoslavia to estimate defined needs, prioritise and evaluate methods
used. Around 30% of war victims reported to be wounded were found to be in need
of physical rehabilitation. Priority was given to the 5% with severe disabilities
caused by amputations, spinal cord injuries and traumatic brain injuries. Most of
the infrastructure was destroyed and WHO supported a community based
rehabilitation approach (CBR). Evaluating this type of service delivery became
extremely difficult under present circumstances. Waves of refugees rolled both
within the republics and over the borders demonstrating both the needs and
problems listed in the template referred to. The CBR service delivery worked out
satisfactorily with high patient satisfaction. Limited medical training greatly
improved the situation for the personnel. Even in a disaster situation research
is needed for proper decision-making and to gain experiences for future aid.
PMID- 9658506
TI - Social support, social disability and their role as predictors of depression
among patients with congestive heart failure.
AB - The purpose of this study was to assess the effect of social support variables,
personality, clinical variables (New York Heart Associations classification), and
social disability upon depression. The sample consisted of 119 clinically stable
patients (34 females, 85 males) with symptomatic heart failure, recruited from an
outpatient hospital practice. The patients underwent a brief physical examination
and completed a set of questionnaires. Descriptive statistics were used to
characterise the patients' informal functional network. The analysis revealed
that the intimate social network support (spouses) and primary social network
support (close family) were rated as most supportive. Results from the path
analysis showed that social disability was explained by the two personality
factors, neuroticism and extraversion, and by the severity of disease (NYHA). No
significant effects of the social support variables upon social disability were
detected. Moreover, path-analyses showed that poor intimate network support,
social disability and neuroticism were significantly positively associated with
depression.
PMID- 9658507
TI - Work disability and health-affecting psychosocial problems among patients in
general practice.
AB - Psychosocial problems are often ignored among patients in general practice. By
identifying high risk groups this situation could possibly be altered. This study
aimed to explore if patients in general practice perceiving themselves as work
disabled by at least 50% more often have health-affecting psychosocial problems
than those not work-disabled. In a geographically defined population, 1,058
consecutive adult patients consulting 89 general practitioners were approached
during one regular working day in March 1995. They completed a questionnaire at
home, returning it directly to the department of general practice. Male patients
considered themselves work-disabled more often than female patients. All
psychosocial problems except having a demanding caregiving task were more common
among the work-disabled. The doctors should bear in mind that work-disabled
patients more often than other patients have concomitant health-affecting
psychosocial problems. Granting long-term sick leave or a disability pension may
not be the only management needed.
PMID- 9658508
TI - Disability pension in Malmohus county: aspects on long-term financial effects.
AB - The purpose of this study was to estimate the financial costs of disability
pension in order to compare the financial burden and the numerical distribution
of disability pension by main diagnostic groups. During three months all new
disability pensions (n = 944) granted in Malmohus county were registered. During
a follow-up of approximately two and a half years, 40 subjects died and 15
pensions expired. The predominating diagnoses were musculoskeletal diseases,
mental disorders including alcohol dependence, cardiovascular and neurological
diseases. To analyse whether these proportions changed when the extent of the
pension, age at pension and the retirement allowance were considered, the present
value of the total retirement allowances was calculated. The ranking of the four
predominating diagnosis categories was not affected by the extent of the pension
or the age at which the pension was granted. Thus, musculoskeletal diseases still
predominated, although the proportion decreased. Among unemployed subjects,
mental disorders made the largest contribution to the total expenditure. The
results gained may be used in further research where alternatives to disability
pension for different groups of patients and/or diagnoses are investigated.
PMID- 9658509
TI - Comparison of stress, job satisfaction, perception of control, and health among
district nurses in Stockholm and prewar Zagreb.
AB - The increasing number of studies of stress among nurses in the last two decades
have mainly dealt with nurses in hospitals. A few studies have included community
based nurses. However, no comparative studies of district nurses in different
countries have been published. We have conducted a study to identify sources of
stress, job satisfaction, perceived demands, control and health among district
nurses (DNs) in Zagreb (Croatia) and Stockholm (Sweden), working in a polyvalent
health care organization. Data were obtained regarding altogether 305 district
nurses by means of self-administered questionnaires using identical methods and
items, with response rates between 88% and 95%. In general, district nurses
reported high levels of job-related stress, satisfaction and control.
Organizational sources of stress, such as ongoing changes in the primary care
organization, and reorganization of tasks, were of importance for the district
nurses in Stockholm. They reported also more job satisfaction and commitment than
the district nurses in Zagreb. The district nurses in Zagreb had significantly
higher level of "lack of resources". They displayed significantly higher scores
of psychological demands but also a greater feeling of control than the district
nurses in Stockholm. Significant differences were also found between the groups
in ranking of self-reported stressors. Thus results show that differences in work
organization and in essential resources have a substantial impact of perceived
stress, job satisfaction, and on the generality both of single association and on
the applications of models.
PMID- 9658510
TI - Children's residential exposure to environmental tobacco smoke varies greatly
between the Nordic countries.
AB - OBJECTIVE: To assess similarities and differences in the Nordic countries
regarding ETS (environmental tobacco smoke) exposure in young children. DESIGN: A
population-based cross-sectional study comprising a randomly selected sample of
5,500 households which included a child born in 1992. Data were collected using a
mailed anonymous questionnaire. RESULTS: While the prevalence of household
smoking was similar in all countries, there was a great difference between the
countries with regard to child ETS exposure. Finnish parents were more likely
than all other Nordic parents to protect their children from ETS and the
situation was worst in Denmark and Iceland, where almost half of all households,
and nine out of ten households containing daily smokers, exposed their children.
Approximately eight out of ten current and former smokers in all countries stated
that they had made efforts to change their smoking habits because of their
children.
PMID- 9658511
TI - Social functioning of elderly coronary heart disease patients.
PMID- 9658512
TI - Indices of need and social deprivation for primary health care.
AB - This study aimed to examine two indices of need, the underprivileged area (UPA)
score and a Swedish Care Need Index (CNI, in Swedish vardbehovsindex) with
weightings from British and Swedish GPs respectively, and an index of material
deprivation, Townsend score at SAMS (Small Area Market Statistics) level and at
municipality level for the whole of Sweden. One third of primary health care
physicians from the whole of Sweden received a questionnaire about their
workload. CNI, UPA and Townsend scores were calculated using information from the
Swedish census of 1990 and the registers of unemployment and migration for 1992.
The Swedish GPs weighted some of the variables quite differently from the GPs in
the UK. This may be important, especially at the SAMS level. The GPs in both
countries considered that older people living alone contributed most to their
workload. However, in Sweden the physicians ranked foreign-born people high
compared with the English doctors, and in England the GPs ranked children under
five years much higher than the doctors in Sweden. The correlation between the
scores was high.
PMID- 9658513
TI - Quality of palliative care: why nurses are more valued than doctors?
PMID- 9658514
TI - How to measure sickness absence? Literature review and suggestion of five basic
measures.
AB - OBJECTIVE: To examine different sick-leave measures used in sickness absence
research, and to suggest a systematic way of assessing sickness absence. METHODS:
A review and analysis of five major studies on sick-leave performed 1983-1988
with an epidemiological approach. RESULTS: Terminology and measures used varied
in the different studies reviewed. The choice of a certain measure was seldom
discussed in relation to the aim of the study. Based on the review five measures
are suggested: frequency, length, incidence rate, cumulative incidence and
duration. The definition of incidence rate is new and is a measure useful in
studies of recurrent events within epidemiology. CONCLUSIONS: We have reviewed
sick-leave measures previously used in the literature and suggested five basic
measures for assessing sick-leave.
PMID- 9658515
TI - Examining what self-rated health question is understood to mean by respondents.
AB - The aim of this methodological study is to examine what self-rated health is
understood to mean by survey respondents. The data are derived from semi
structured (re-)interviews with 42 middle-aged participants of the 1994 Finnish
Survey on Living Conditions. When the respondents are asked to describe their
present health, the results show concrete, contextual, and partly contradictory
conceptions of "health". Health is presented primarily as absence of ill-health,
but also connected to personal experience and life situation, and as a result of
action. Second, when assessing self-rated health all respondents base their
assessments on ill-health, modified by the severity, duration and restrictions
posed by ill-health. Further analysis shows that some respondents base their
assessments also on fitness and health behaviour. The results suggest that in
addition to the medical model of health, adopting health promotion messages and
"healthy" lifestyles are important factors contributing to health assessments.
PMID- 9658516
TI - Response rate according to title and length of questionnaire.
AB - The purpose of this study was to investigate how response rates to a postal
questionnaire are affected by title and length of the survey instrument. Five
questionnaires, which differed according to title and length, were designed. Each
questionnaire was mailed to a random sample of one thousand Norwegian women aged,
35-49 years. A total of 3,106 questionnaires were returned (62.1%). The highest
response rate (70.2%) was achieved by a two-page questionnaire entitled "Women
and Cancer". An otherwise identical questionnaire entitled "Oral Contraceptives
and Cancer" had a response rate of 60.7%. Questionnaires entitled "Women and
Cancer" with a length of four and six pages had a response rate of 62.8% and
63.3%, respectively. The four page questionnaire entitled "Women, Lifestyle and
Health" had the lowest response rate of 57.1%. This study shows that in a general
population of Norwegian women the title of a postal questionnaire influences the
response rate. The results indicate that although the shortest questionnaire had
the highest response rate, the most extensive survey instrument did not have the
lowest response rate. The distribution of risk factors for breast cancer did not
vary according to response rate or design of questionnaire. The overall findings
of this study suggest that the benefits from the increased information obtained
from extensive postal questionnaires out-weighs a potential non-response bias due
to a somewhat lower response rate.
PMID- 9658517
TI - [Value and limits of conventional mediastinoscopy in preoperative evaluation of
primary bronchial cancer].
AB - PURPOSE OF THE STUDY: Retrospective evaluation of conventional mediastinoscopy in
the preoperative staging of primary lung cancer. METHODS: Between 1978 and March
1997, 117 consecutive patients underwent conventional mediastinoscopy in the
preoperative staging of primary lung cancer, after imaging had shown mediastinal
lymph nodes larger than 1.5 cm. RESULTS: In 8 instances no material was found at
mediastinoscopy, in 38 the lymph nodes showed no tumorous infiltration, and in 71
the lymph nodes were metastatic. 48 patients underwent thoracotomy in the same
stage, with resection achieved in 41. Contraindications for thoracotomy (in 69)
were N2 (45) or N3 (11) disease adn/or small cell lung cancer (18). Mediastinal
lymphadenectomy was performed in 26 of the 41 patients who underwent lung
resection; half of those with negative nodes at mediastinoscopy had in fact N2
disease, with involvement of 2 areas of more in half. There were no deaths due to
mediastinoscopy but 4 complications. CONCLUSIONS: A favorable mediastinoscopy is
not synonymous with resectable disease, nor does it exclude N2 disease; it does
however serve to avoid unnecessary thoracotomies in more than half of cases.
PMID- 9658518
TI - [Is infra-inguinal venous bypass less successful in the woman?].
AB - In the present study the influence of gender in peripheral arterial
reconstructions was evaluated. Between 1986 and 1990 we performed 173
infrainguinal vein bypass procedures in 117 men and 56 women. All procedures were
carried out for chronic critical leg ischaemia. Bypasses in men were femoral to
popliteal in 68%, and femoral to infragenicular in 32% in cases. The
corresponding values in women were 52% and 48%. Perioperative 30-day mortality
was 2% in men and 2% in women. Long-term survival at 5 years was 50% in men and
44% in women. Life-table primary 5-year patency rates were 81% for men and 74%
for women. Limb salvage results at 5 years were 87% for men and 84% for women.
The results indicate that in our experience with autogenous vein longterm graft
patency and limb salvage results in women are identical to those obtained in men.
Infrainguinal arterial reconstruction can be performed in women with mortality
rates similar to those of men.
PMID- 9658519
TI - [Paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies in ovarian
carcinoma].
AB - We report the case of 71-year old Caucasian woman with ovarian cancer, who
developed paraneoplastic cerebellar degeneration (PCD). Pathognomonical anti Yo
antibodies could be identified in serum specimens. We describe the history and
clinical presentation and summarise the disease.
PMID- 9658520
TI - [Pro or contra Papanicolaou cytologic smear every 3 years].
AB - OBJECTIVE: To analyse the possibility of three-yearly screening for cervical
cancer after two consecutive normal annual smears. METHOD: Review of the
literature. RESULTS: In Switzerland 78% of women are screened spontaneously for
cervical cancer. For 70% of this group the last smear was less than 18 months
before. In other European countries or in North America programmed screening is
every 3 or even 5 years. A lowered mortality rate is observed depending on the
interval between screening. The benefit is only 2.7% between 3-yearly (90.8%) and
yearly smears (93.5%). Finding an oncogenic HPV [16, 18, 31, 45] whilst
investigating low grade cervical intraepithelial neoplasia (CIN1) is associated
with a 17% risk of conversion into high grade cervical intraepithelial neoplasia
(CIN3) within 3 years. CONCLUSION: In Switzerland the conditions for screening on
a 3-yearly basis are not fulfilled. We recommend an interval of only 2 years
after 2 normal annual smears.
PMID- 9658521
TI - [Unexpected cause of abdominal pain].
PMID- 9658522
TI - [Surgery of rectal carcinoma: 1997 status assessment].
PMID- 9658523
TI - Anatomic basis of Tonnis' triple pelvic osteotomy for acetabular dysplasia.
AB - Dysplasia of the hip in adults can be treated by a pelvic osteotomy. In order to
assess pelvic anatomy in relation to surgical approach and osteotomy sites, 12
cadaver hips were studied. A triple pelvic osteotomy as described by Tonnis [6]
through ilium, pubis and ischium was performed, followed by an intrapelvic and
anterior and posterior dissection of the hip. At the ischium, the pudendal and
inferior gluteal neurovascular bundles are most at risk medially and proximally
respectively. Much less in danger is the sciatic n. as it runs 1 to 3 cm lateral
to the osteotomy site. At the pubis osteotomy the femoral v. lies close on the
bone and is prone to damage. The artery lies further off the bone. The ilium
osteotomy starts just proximal to the anterior inferior iliac spine and exits
posteriorly at the sciatic notch. Here the sciatic n. and the superior gluteal
neurovascular bundle may be damaged. The practical surgical implications of these
three osteotomies are discussed, especially with respect to the requirement of
meticulous subperiostal dissection and accurate placement of retractors.
PMID- 9658524
TI - Anatomic bases of tongue flaps.
AB - The morphological structure of the lingual a. was studied in 50 dissected and 14
vascular cast specimens. The course of this artery is divided into 4 segments:
the original segment, the segment within hyoglossus, the ascending and the
horizontal segments of the deep lingual a. The root of the tongue is supplied by
2 to 3 root branches of the lingual a., the ascending palatine a. and the
tonsillar a. The body of the tongue is nourished on averaged by 25 arterial
branches from the deep lingual a. The ventral surface of the tongue, as well as
the sublingual gland and the floor of the mouth, is supplied by the sublingual a.
The termination of the lingual a. The termination of the lingual a. anastomoses
with the submental branch of the facial a. to form the lingual frenal a. Except
for a submucous arterial network on the dorsum of the tongue, all blood vessels
are separated completely by the lingual septum, through which arterial
anastomoses (2.0 mm in diameter) can be found occasionally.
PMID- 9658525
TI - Morphologic studies of the venous drainage of the tongue.
AB - The aim of this work was to study the role of the venous drainage of the tongue
in tongue inspection in traditional Chinese medicine and tongue-flap surgery.
Thirty-two adult cadavers were observed, including 7 venous corrosivecast
specimens. The decreasing order of venous drainage of the tongue, based on the
diameter of the vein and size of its drainage area, was the accompanying v. of
the hypoglossal n., the epiglottic valleculate v., the accompanying v. of the
lingual n., the lingual root v. and the accompanying v. of the lingual a. The
veins constituting the picture of the tongue seen in sublingual collateral
inspection were the companion vv. of the hypoglossal and lingual nn. The pedicle
of a tongue flap must maintain efficient venous drainage canal.
PMID- 9658526
TI - Anatomic basis of chronic perineal pain: role of the pudendal nerve.
AB - Our anatomic findings have led us to define conflictual relations that may be
encountered in their course by the pudendal n. and its branches. Starting from
the clinical study of a group of patients suffering from chronic perineal pain in
the seated position, we have defined, beginning with the cadaver, three possible
conflictual settings: in the constriction between the sacrotuberal and
sacrospinal ligaments; in the pudendal canal of Alcock; and during the straddling
of the falciform process of the sacro-tuberal ligament by the pudendal n. and its
branches. Consequently, considering so-called idiopathic perineal pain as an
entrapment syndrome, the clinical and neurophysiologic arguments and infiltration
tests have led us to define a surgical strategy which has currently given 70% of
good results in 170 operated patients. Earlier diagnosis should improve on this.
PMID- 9658527
TI - Anatomic study of the umbilical vein and ductus venosus in human fetuses:
ultrasound application in prenatal examination of left congenital diaphragmatic
hernia.
AB - For clinicians it is very difficult to evaluate the prognosis of a left
congenital diaphragmatic hernia (CDH) at prenatal ultrasound examination.
Surgical studies show that the presence of a large part of the liver in the chest
is a criterion of poor prognosis. However, ultra-sonography encounters some
difficulties in determining the precise position of the liver in the thoracic
cavity. The aim of this anatomic study was to define the relationship between the
position of the liver and the path of the ductus venosus and of the umbilical v.,
which are easily recognizable at prenatal sonography. Twenty dead fetuses were
used for the study (12 with a left CDH and 8 without). All fetuses underwent
radiographic assessment, anatomic dissection and cross-sectional study. The angle
between the umbilical v. and the ductus venosus in different planes was measured.
The more the liver was in the thorax, the greater was the angle between the
ductus venosus and the sagittal plane, and the less the angle between the ductus
venosus and the umbilical v. These angles can be easily measured by prenatal
ultrasound examination of the fetus. Our findings suggest that it is now possible
to offer the clinician a new and reliable way to determine the prognosis of a
left CDH before birth.
PMID- 9658528
TI - Morphometric evaluation of the sacral dorsal root ganglia. A cadaveric study.
AB - An anatomic study of the sacral dorsal root ganglia (DRG) was performed to
determine the location and dimensions of the S1-4 DRGs and to correlate this
information to sacral nerve root ganglion lesions. S1 DRGs were located in the
intraforaminal region in 55-60% and in the intracanalar region in 40-45%. S2 DRGs
were in the intraforaminal region in 15-50% and in the intracanalar region in 50
85%. All the S3 and S4 DRGs were located in the intracanalar region. None of the
sacral DRGs was located in the extraforaminal region. The intraforaminal position
of the S1 and S2 ganglia renders them vulnerable to compression caused by sacral
fractures involving the sacral foramina because of the little space available for
these ganglia in the foraminal region. The S1 DRG, with its its relatively larger
dimensions and its intracanalar position relative to the other sacral DRGs, may
be susceptible to compression by the L5-S1 disk herniation. Its intraforaminal
position may predispose it to injury during S1 or S2 pedicle screw placement.
PMID- 9658529
TI - Intracranial course and relations of the hypoglossal nerve. An anatomic study.
AB - This anatomic study describes the course and intracranial relations of the
hypoglossal n. in 32 cadavers. The rootlets of the nerve emerged as a fan-shaped
distribution (23.44%) or in two bundles (76.56%) and converged towards the
hypoglossal canal in the subarachnoid space before piercing the duramater. In
76.57% of cases the rootlets pierced the dura mater in two separate apertures,
less commonly through the same aperture (21.87%), and in rare cases through three
individual apertures, as in one of our cases. The distance between the two
apertures varied from 0.6 mm to 8.7 mm. Commonly, the two bundles converged
together and left the skull through one foramen in the skull. However, in some
cases (28.12%), the hypoglossal canal was divided in two by a small bony spicule.
In 23.45% of cases the initial course of the posterior inferior cerebellar a.
(PICA) passed between the two bundles of the hypoglossal n. before ascending
towards the lateral border of the fourth ventricle.
PMID- 9658530
TI - Technique for injection of the lumbar vertebral venous plexuses employed in
anatomic, computed tomography and magnetic resonance imaging studies.
AB - The aim of this study was to develop a technique for injection of the vertebral
venous plexuses allowing anatomic, computed tomography (CT) and magnetic
resonance imaging (MRI) studies of the same anatomic specimen. It proved in
practice that only a correctly adjusted mixture of different agents allowed
attainment of this objective. This mixture, composed of gelatin, gadolinium and
minium, enabled us to attain this end. The description of the technique of
injecting the vertebral venous plexuses, the difficulties encountered and the
results of the different imaging techniques are analysed in this study without
entering into details of the anatomic description. The core of the study consists
of 11 unembalmed subjects. Three were injected with gelatin mixed with
gadolinium, one with latex mixed with minium, one with latex mixed with
gadolinium, and 6 with gelatin mixed with both gadolinium and minium. Only the
mixture of gelatin-gadolinium-minium allowed study of the same anatomic specimen
in terms of anatomy, CT and MRI. Two different MRI sequences are described,
evidence of the different properties of the injection mixture (gelatin,
gadolinium). The latex-minium mixture gave good CT density but was unsuitable for
MRI studies. Numerous artifacts caused interference with the radiologic images,
calling for perfect injection technique. The use of several radiologic techniques
for a single cadaveric injection allows better correlation of the images, and
comparison and verification of results between the techniques.
PMID- 9658531
TI - Study of the inferior oblique muscle of the eye by MRI.
AB - The utility of the inferior oblique m. radioanatomical study by a FLASH 3D
sequence in magnetic resonance imaging (MRI). Twenty eyes (ten healthy volunteers
aged 21-32 years, without any history of significant ocular pathology) were
explored by MRI (1 Tesla; cranial coil) and comparisons were made between spin
echo (SE) T1 sequence (through the neuro-ocular and coronal planes; thickness of
slices = 3 mm) and a gradient echo FLASH 3D sequence (thickness of slices = 1
mm). This enabled a mm by mm reformation of the inferior oblique m through the
frontal-oblique plane, made possible by new SE T1 sequences through the same
plane. Position, height, and signal of the m. were estimated. The mean frontal
angle formed by the muscle and the sagittal axis measured 29 degrees for the
right eye and 27 degrees for the left eye. The muscle was always identifiable in
the reformation despite its thin dimensions: 1.9 mm (1.5 - 2.8) on the right and
2 mm (1.7 - 2.5) on the left, in low signal silhouetted by the high signal of
orbital fat. Thus, thanks to mm by mm reconstructions using FLASH 3D sequence, a
good radioanatomic study of the inferior oblique m. by MRI is possible. This
could be useful particularly for the strabismus of children.
PMID- 9658532
TI - Anatomic approach to the parametrium: value of computed tomographic in vitro
study compared to dissection.
AB - The aim of this study is to describe the morphology of the normal parametrium by
correlating the slices obtained with computed tomography of 12 female cadavers
studies after intravascular injection of latex with the dissection findings in 6
of the these patients. the upper limit, represented by the isthmus was defined by
the uterine a. and/or a superficial uterine v. and/or the coronary v. (Charpy).
The lower limit corresponded to the insertion of the levator ani mm. at the
junction of the middle and inferior thirds of the vagina. The paracervical and
paravaginal tissues above the levator ani m. and medial to the pelvic fascia
covering these muscles were perfectly visualized. The posterior limit, formed by
the lateral ligament of the rectum and/or the sacrouterine ligaments, and the
anterior limit determined by the umbilico-vesical fascia were more difficult to
demonstrate. In this study the parametrium appeared as a highly vascular and
essentially venous connective structure with a variable morphology dependent on
the uterine position.
PMID- 9658534
TI - Partial ureteral duplication in an inverted Y with epididymal ureteric ectopia
and intrasinusal ureteral junction.
AB - Partial ureteral duplication in an inverted Y is evidenced by the presence of a
ureter duplicated at a variable level before reaching the bladder, in either an
orthotopic or an ectopic position. A case of ureteral duplication at the level of
the renal hilum with opening of a ureter at the level of the epididymis is
reported. The description of this original case is compared with the data in the
literature. The stages of organogenesis of the superior excretory pathway leading
to ureteral ectopia and ureteral anomalies of number are reviewed.
PMID- 9658533
TI - Anatomy of spontaneous splenorenal and gastrorenal venous anastomoses. Review of
the literature.
AB - Portal hypertension is characterised by the development of a collateral
portocaval circulation. Among these venous reroutings, some are situated
posteriorly in the left subphrenic compartment. These are the spontaneous
splenorenal and gastrorenal anastomoses. Their incidence is estimated at around
16%. On the one hand, there are the direct shunts, which anastomose the spelling
v. to the left renal v., of an anecdotal nature, and on the other the spontaneous
indirect splenorenal shunts, characterised by the presence of a complete
neurovascular pedicle traversing the gastrophrenic ligament. This relates to the
gastric collateral v., which is connected to the left renal v. via the inferior
v. of the left crus of the diaphragm and the middle capsular v., hence the name
"gastro-phreno-capsulo-renal shunt". At an advanced stage of portal hypertension
these splenorenal shunts may acquire a major caliber and behave like actual
surgical shunts.
PMID- 9658535
TI - Anomalous pancreatico-biliary ductal union with cystic dilatation of the bile
duct.
AB - We report, in an adult, an asymptomatic association between cystic dilation of
the bile duct (type IV A in Todani's classification) and anomalous pancreatico
biliary ductal union (APBD) with stones in a long common channel. In APBD, the
connection between the common bile duct and the main pancreatic duct is located
outside the duodenal wall andis therefore not under the influence of the
sphincter of Boyden. An abnormally long common channel is in excess of 15 mm. Two
types of convergence anomalies are defined according to whether the bile duct
opens into the main pancreatic duct (BP) or the main pancreatic duct into the
bile duct (PB). In APBD, there is probably a reverse pressure gradient between
the bile and pancreatic ducts, with regurgitation of pancreatic juice into the
bile duct, repeated attacks of cholangitis, stenosis and cystic dilatation. A
long common channel is associated with a higher incidence of carcinoma of the
gall bladder of the bile duct.
PMID- 9658536
TI - [The setting up of an integrated veterinary business approach in dairying].
AB - In addition to the continuous provision of veterinary care, another important
aspect of a veterinarian's work is his or her advisory function in farm
management. Too few veterinarians fulfil this function. This can only be done
successfully if the dairy farmer and veterinarian solve a number of problems. An
integrated management plan incorporation a step-by-step approach should make this
possible.
PMID- 9658537
TI - [The proximal sesamoid bone of the horse; vascular and neurologic
characteristics].
AB - Sesamoiditis is characterized clinically by repeated lameness and radiologically
by changes in the proximal sesamoid bones. This thesis, which was defended in
June 1997, investigated two characteristics of sesamoiditis, namely the arterial
blood supply and the innervation of the proximal sesamoid bones, in order to gain
more insight into the etiopathogenesis of sesamoiditis. Experiments with patient
material showed that the proximal sesamoid bones have an enormous arterial
reserve, due in part to the formation of an arterial shift. Moreover, the
sesamoid bones have their own sensory innervation, provided by a branch of the
medial and lateral palmar nerve. This branch is called the sesamoid nerve in this
article. A special technique was developed to anaesthetize this nerve and can be
used for further differentiation of pastern lameness. That the sesamoid bones are
sensitive to pain was demonstrated by detection of the so-called nociceptive
neuropeptides, substance P and calcitonin gene-related peptide, which are
specifically involved in pain sensation. However, the adjacent ligament appear to
be even more sensitive. The etiopathogenesis of sesamoiditis is discussed, as are
a number of clinical implications of pain in the sesamoid bones. A number of
potential future developments are mentioned.
PMID- 9658538
TI - [Reproduction of the horse: the use of different dilutions of stallion sperm].
PMID- 9658539
TI - [Health and social status].
PMID- 9658540
TI - [Hospital infection caused by Aspergillus--an overview of etiology and
possibilities for prevention].
AB - During the last decades a sharp increase in the occurrence of invasive
aspergillosis associated with a high mortality has been observed. This fact is
mainly due to an increase in the number of immunosuppressed patients. Nosocomial
aspergillosis usually is of exogenous origin and often related to building
construction and reconstruction, road construction, contaminated ventilation
systems and contaminated soil of pot plants. By institution of suitable
prophylactic measures a reduction of incidence and mortality of invasive
aspergillosis can be achieved. This review gives a short introduction into the
epidemiology, pathogenesis and diagnosis of invasive aspergillosis and, in the
second part summarizes internationally recommended guidelines for prevention of
this severe complication.
PMID- 9658541
TI - Social inequalities in disability-free and healthy life expectancy in Austria.
AB - The purpose of this study is to describe socioeconomic differences in the health
status and mortality of the Austrian population. Socioeconomic differentials in
disability and self-perceived health are studied on the basis of educational
groups. The data are drawn from the 1991 Austrian micro-census on health and from
linked death and census records for the years 1981/82. The maximum number of
years lived between ages 30 and 75 is divided into years lost, years lived in
disability or poor health and years lived without disability or in good health.
Our findings clearly indicate a correlation between higher education and higher
life expectancy and lower morbidity. Comparing the two indicators, more years are
lived in poor health than in severe functional disability. The two concepts of
health lead to different conclusions when results for men and women are compared:
women live more years in disability than men but fewer years in poor health.
Differences between educational groups are lower when the concept of self
perceived health is applied.
PMID- 9658542
TI - Survey of sport injuries in physical education students participating in 13
sports.
AB - A protocolled interview was carried out of 150 physical education students to
specify retrospectively all sports injuries sustained during their training. This
study analyses the frequency, severity and location of injuries sustained by a
population group participating in 13 different sports. On average more than three
injuries were encountered per student over a mean period of 2.35 years. 74% of
all 482 recorded injuries were sustained by males. The sports associated with the
highest rate of injuries were gymnastics, skiing and athletics followed by ball
games. The most frequently injured body regions were the ankle and the hand. 29%
of the injuries were regarded as being severe.
PMID- 9658543
TI - [The postictal state. A clinically oriented observation of patients with
epilepsy].
AB - Epileptic seizures are followed by dynamic alterations in neurologic function in
the postictal period which have received little attention by clinicians over a
long period of time. We therefore retrospectively studied videotapes of 160
patients with focal epilepsy who underwent presurgical evaluation, for the
occurrence of postictal symptoms to determine whether these phenomena have any
localizing or lateralizing value in defining the seizure onset zone. RESULTS: (1)
We found postictal paresis in 22 of 160 patients (18.8%) in each case
contralateral to the hemisphere of seizure onset. (2) 'Perservative' automatisms
which start during the ictus and continue in the postictal period occurred in
25.2% of 135 patients with temporal lobe epilepsy but not in patients with
frontal lobe epilepsy. (3) Sexual automatisms defined as manipulations of the
genitals were found exclusively in patients with temporal lobe epilepsy (in 5.9%
of 135 patients). (4) Postictal 'Nose-wiping' was evident in 51.3% of 76 temporal
lobe epilepsy patients but only in 12.0% of 25 extratemporal lobe epilepsy
patients and was performed with the hand ipsilateral to the hemisphere of seizure
onset in 86.5% of all temporal lobe seizures. (5) Postictal language disturbances
were observed only in patients with temporal lobe epilepsy (34% of 97 patients)
and pointed to a seizure onset in the dominant hemisphere in 80.8%. We conclude
that postictal phenomena can provide reliable information for the localization of
the seizure onset zone in patients with complex partial seizures. Thus, more
attention should be given to the postictal state during presurgical epilepsy
monitoring.
PMID- 9658544
TI - [Aspects of laterality for surgical indications in middle ear diseases].
PMID- 9658545
TI - [How dangerous is genetically engineered food].
PMID- 9658546
TI - [LDL subfractions and coronary heart disease--an overview].
AB - Low density lipoproteins are heterogeneous in particle size, density, and
physical as well as chemical properties. Regarding size and density, LDL can be
divided into two main profiles, LDL pattern A with elevated concentration of
large, buoyant LDL particles and LDL pattern B with increased concentration of
small, dense LDL particles. The latter is particularly expressed in insulin
resistance and is associated with elevated serum triglycerides and reduced
concentrations of HDL and particularly HDL2 cholesterol. The LDL profile of
increased concentration of small, dense LDL particles has shown to be associated
with an increased risk of cardiovascular events. The LDL profile is partly
genetically determined, but can be improved by non-pharmacological (exercise,
diet) and pharmacological intervention. It remains to be confirmed whether the
LDL subfraction profile is an independent lipid risk factor besides HDL2
cholesterol and triglycerides, but it is certainly a valuable indicator assessing
metabolic cardiovascular risk.
PMID- 9658547
TI - [Heart operations for heart tumors in Germany--results of 1996 survey].
AB - In the Federal Republic of Germany, no data existed regarding the frequency of
open heart surgery for excision of cardiac neoplasms. Therefore, a standard
questionnaire concerning heart tumors was sent to all 77 German heart centers
performing cardiac surgery. Data from 65 of the 77 heart centers (= 84%) are
finally available: 187 patients were operated upon for myxomas, only 44 upon for
non-myxomatous cardiac tumors (28 of them with malignant primary or secondary
lesions of the heart). In 1996, 0.32% (231/72,763) of all surgical procedures
using a heart-lung machine (registered 72,763 of 87,372 total) were aimed at
excision of heart tumors. Based on surgical data, the incidence of solely the
primary tumors of the heart in Germany is at least 3 per million population per
year (253 tumors/81.814 million inhabitants). Even if small tumors are
asymptomatic and remain undetected, today, the majority of primary tumors of the
heart will be revealed by echocardiography, computer tomography, and magnetic
resonance imaging, and these patients are usually referred to operation. Thus, in
Germany, about 0.3% of operations using a heart-lung machine were performed for
cardiac tumors-among these, myxomas are clearly predominant.
PMID- 9658548
TI - [Advantages in using intravascular ultrasound in percutaneous transluminal
coronary angiography].
AB - Recent randomized clinical trials reported a reduction of restenosis using
intracoronary stents and suggested that this restenosis reduction is a result of
the higher immediate luminal gain in comparison to conventional percutaneous
transluminal coronary angioplasty (PTCA). The hypothesis of this study is based
on the assumption that IVUS guided PTCA leads to equivalent long term PTCA
results as compared to PTCA and the additional placement of a stent. Thus, the
purpose of this non-randomized single center study was to evaluate (1) the safety
and efficacy and (2) the long term outcome of vessel size adapted PTCA in
patients with native coronary lesions. From April 1995 to March 1996 the
morphological dimensions of the target lesions were determined in 107 patients
with 108 lesions by intravascular ultrasound prior to conventional balloon
angioplasty. Quantitative parameters of the vascular dimensions were assessed on
line and the diameter of the balloon catheter was adapted to the external elastic
membrane (EEM) at the lesion site minus 10%. Using this strategy, mean balloon
diameter was 4.1 +/- 0.5 mm. Acute and one year clinical follow-up results were
obtained in all 107 patients. Angiographic success was defined as a final percent
diameter stenosis of < 30%. The following criteria determined by
postinterventional IVUS were also used to define a successful PTCA: luminal CSA
gain of > 30% with an angiographically patent flow (TIMI 3). Acute events
occurred in two patients (one death and one successful acute surgical
revascularisation). During one year follow-up, 11 patients had a clinical event
including death, Q-wave MI, surgical revascularisation, and repeat PTCA. In 83
patients (78%), control angiography was performed and revealed an angiographic
restenosis rate of 21% using the NHLBI criterion of a diameter stenosis > 50%
CONCLUSION: The use of balloon diameters following these measurements is safe in
the acute setting with a low number of in hospital events and effective in
reducing clinical events as well as angiographic restenosis rates during one year
follow-up. These promising results warrant verification in larger scale
randomized trials.
PMID- 9658549
TI - [Optimal expansion of the multi-link stent. An in vitro study with high
resolution roentgen technique].
AB - It has been speculated that high pressure implantation may improve the results of
coronary stenting. However, this method bears the risk of persistent dissection
and may increase late lumen loss. Presently, there is no consensus about the
optimal stent implantation technique with the regard to balloon size and
pressure. To elucidate this question an experimental study was performed in a
coronary stenosis model. 3.5 mm Multi-Link (ML) stents were implanted in 3.3 mm
silicone rubber tubes containing 50% concentric narrowings. Three implantation
techniques were applied: 1. The standard technique using the conventional ML
delivery system with a compliant balloon (ML-ST). 2. A new deployment method with
a high pressure delivery system (ML-HP). 3. "Focal postdilation" using the ARC
catheter, which has a special balloon with an inner compliant and an outer non
compliant section (ML-ARC). For comparison, the Palmaz-Schatz stent was implanted
by using a high pressure balloon. Stent expansion was imaged by magnification
radiography. Minimal lumen diameter within the stent (MLD) and the lumen diameter
outside the stent (BD) were measured after dilations with 6, 9, 12, 15, 18, and
21 atm. The relation of the BD to the MLD was used as an index of vessel trauma.
The results lead to the following conclusions: 1. A complete apposition to the
vessel wall for a balloon/vessel relation of 1.1:1 could not be reached with
pressures below 9-15 atm. The increase of the pressure beyond 15 atm resulted
only in a minimal additional lumen. 2. Compared to the Palmaz-Schatz stent the
recoil of the ML stent was significantly lower. 3. For all three implantation
techniques the ML-ARC showed the best results with the maximal dilation of the
stenotic vessel-area and the minimal expansion of the vessel outside the stent.
PMID- 9658550
TI - [Repetitive monomorphic ventricular tachycardia (Gallavardin type): clinical and
electrophysiological characteristics in 20 patients].
AB - Repetitive monomorphic ventricular tachycardia (RMVT) is defined by the presence
of numerous monomorphic isolated, premature ventricular complexes, couplets, and
runs of unsustained ventricular tachycardia having the same morphology in
patients without structural heart disease. Patients with RMVT mostly demonstrate
the typical left bundle branch block morphology with normal or rightward axis
during tachycardia. At our institution, 20 patients with RMVT have been
systematically studied: a syncope had occurred in 35% of our patients, in three
cases a syncope was the first manifestation of the RMVT. Of our RMVT patients,
25% developed sustained episodes (> 3 min) of ventricular tachycardia as
documented by Holter ECG. The salvos of ventricular tachycardia are generally
short in RMVT. This behavior and the typical exercise dependence differentiates
RMVT from paroxysmal sustained idiopathic ventricular tachycardia. Exercise
testing is mandatory for correct diagnosis of RMVT. In our institution, 85-90% of
RMVT patients demonstrated runs of ventricular tachycardia or sustained
ventricular tachycardia while on a treadmill (exercise test) or during
isoproterenol infusion. RMVT was inducible by programmed electrical right
ventricular stimulation in only 13% of our patients. Therefore, in patients with
suspected RMVT programmed electrophysiological stimulation is only useful to
differentiate a ventricular tachycardia from a supraventricular tachycardia with
bundle brunch block or in patients with unexplained syncope. The prognosis is
considered generally good; in our patients no life threatening ventricular
tachyarrhythmias were observed during a follow-up of up to 4 years. Verapamil and
beta-adrenoceptor antagonists generally offer symptomatic improvement. In some
cases treatment with a class III antiarrhythmic agent is necessary. While drug
refractory paroxysmal sustained idiopathic ventricular tachycardia can be abladed
with both immediate and long-term success, catheter ablation of RMVT is only
rarely indicated.
PMID- 9658551
TI - [High frequency catheter ablation in young patients with permanent junctional
reentry tachycardia and ectopic atrial tachycardia].
AB - Ten young patients with a median age of 10.5 (range: 6 to 31) years suffering
from the permanent form of junctional reciprocating tachycardia (PJRT; n = 7) and
ectopic atrial tachycardia (AET; n = 3) were treated by transcatheter
radiofrequency current application. Indications for interventional therapy were
failure of medical therapy after a median of 3 antiarrhythmic drugs in all
patients, syncope in 1, and impaired left ventricular function in 4 patients
(PJRT n = 3, AET n = 1). The intervention was primarily successful in all
patients. Median fluoroscopy time during the ablation procedure was 17 (10 to 70)
minutes. A median of 3 (1 to 14) radiofrequency (500 kHz) pulses was delivered at
a target temperature of 70 degrees C or with 30 W for 30 s. One patient had a
recurrence of PJRT and was successfully treated by a repeat ablation. After a
median follow-up of 14 (2 to 61) months, all patients are free of drug treatment
and in normal sinus rhythm. Left ventricular function has normalized in patients
with follow-up > 6 months. Radiofrequency catheter ablation was a safe and
effective therapy in young patients with drug-resistant forms of chronic
permanent supraventricular tachycardia.
PMID- 9658552
TI - [Effect of programmed safety margin on function time of modern dual chamber
pacemakers].
AB - In 55 consecutive patients with the same dual chamber pacemaker (Relay,
Intermedics) and different pacing leads, the influence of different safety
margins for pacing on battery current was investigated. 2.8 +/- 0.9 years after
implantation, atrial and ventricular pulse-width thresholds (tRS) (ms) were
determined at 0.5, 1.0, and 2.0 V, and the charge delivered at threshold was
telemetered. If tRS was < 1.50 ms at 0.5 V, an amplitude of 1.0 V was programmed
in the atrium and the ventricule; if tRS was < 1.50 ms at 1.0 V, then an
amplitude of 2.0 V was chosen. Two times the charge threshold (2 x QRS), two
times the voltage threshold (2 x URS), and three times the pulse-width threshold
(3 x tRS) were programmed as the safety margins for pacing. With every safety
margin, battery current (IBat) (microA) was averaged from 5 telemetric readings
in D00 mode with 70 bpm. IBat was significantly lower with 2 x QRS as compared
with 2 x URS (13.43 +/- 1.0 vs. 14.20 +/- 1.2 microA, p < 0.01) and as compared
with 3 x tRS (13.99 +/- 1.2 microA, p < 0.05). Pacemaker longevity derived from
these current data was significantly longer with 2 x QRS (112 +/- 8 months) as
compared with 2 x URS (106 +/- 9, p < 0.01) and as compared with 3 x tRS (108 +/-
8, p < 0.05). If current consumption is compared intraindividually in dependance
on the programmed amplitude, battery current is significantly lower at 1.0 V as
compared with 2.0 V resulting in a mean reduction of 0.63 microA (-4.9%, p <
0.05) and an average gain in longevity of 5 months. This applies to every safety
margin tested. Differences in battery current caused by the safety margins will
translate into a greater gain in longevity in future pacemaker models with
reduced internal current consumption.
PMID- 9658553
TI - [Transient loss of preexcitation by acute coronary ischemia--a case report].
AB - We present a case of WPW syndrome with an accessory pathway in the right free
wall. Two prolonged and failed attempts at radiofrequency catheter ablation of
this accessory pathway in other institutions led to a third attempt in our
hospital. With a 7F catheter in the right coronary artery, transient ischemia in
the right ventricular myocardium developed with consecutive loss of bidirectional
preexcitation within 45 seconds prior to catheter ablation. Removal of the
guiding catheter, while the mapping catheter in the coronary artery was still in
place, was reproducibly followed by the reoccurrence of the preexcitation
pattern. Successful outcome of accessory pathway ablation was achieved by mapping
the right free wall using an intracoronary catheter in the right coronary artery
and ablating the accessory pathway using a modified long vascular sheet.
PMID- 9658554
TI - [Haustration of the ascending aorta as differential diagnosis of aortic
dissection].
AB - Suspected aortic dissection requires undelayed diagnosis by use of imaging
modalities such as transesophageal ultrasound, contrast enhanced computed
tomography (CT), or magnetic resonance imaging (MRI). This case report describes
an asymptomatic man with echocardiographic suspicion of aortic arch dissection.
The discordance with the clinical presentation led to CT, MRI, and eventually to
contrast angiography, eventually confirming extensive haustration of the thoracic
aorta and excluding any acute or chronic dissection. This case demonstrates
haustration of the thoracic aorta as a potential differential diagnostic problem
when solely using ultrasound techniques.
PMID- 9658555
TI - Pseudoacids. II. 2-Acylbenzoic acid derivatives.
AB - Structures of derivatives of cyclic o-acylbenzoic acids, including the chloride,
endo- and exocyclic amides, esters and anhydrides, are examined. 3-Chloro-1(3H)
isobenzofuranone (1), orthorhombic, Pbca, a = 11.616 (5), b = 8.120 (3), c =
15.640 (9) A; 3-methoxy-3-phenyl-1(3H)-isobenzofuranone (3), orthorhombic,
P2(1)2(1)2(1), a = 6.923 (2), b = 8.291 (4), c = 21.551 (8) A; 3-hydroxy-3-phenyl
N-propyl-1(3H)-isoindolone (4), orthorhombic, P2(1)2(1)2(1), a = 8.662 (4), b =
9.551 (7), c = 17.649 (14) A; 3-(N-morpholino)-1(3H)-isobenzofuranone (5),
triclinic, P1, a = 6.172 (4), b = 11.163 (7), c = 17.33 (2) A, alpha = 105.91
(6), beta = 99.85 (6), gamma = 97.57 (5) degrees; 3-(2'-benzoylbenzoyloxy)-3
phenyl-1(3H)-isobenzofuranone (7), triclinic, P1, a = 9.694 (3), b = 10.505 (4),
c = 11.163 (4) A, alpha = 80.58 (3), beta = 80.41 (3), gamma = 76.49 (3) degrees;
bis[1(3H)-isobenzofuranone-3-yl]ether (8), monoclinic, I2/a, a = 15.31 (2), b =
6.111 (12), c = 28.30 (5) A, beta = 101.61 (12) degrees. An open oxoacid tertiary
amide is also described: N-morpholino 2'-benzoylbenzamide (6): monoclinic,
P2(1)/c, a = 6.844 (4), b = 15.696 (8), c = 14.154 (7) A, beta = 99.43 (4).
Pseudoacid derivatives form planar isobenzofuran and isoindole rings, and the
former aldehyde/ketone carbon-heteroatom endocyclic and exocyclic bond distances
show bond length variations which correlate with the relative basicities of the
attached groups. Structures of both endocyclic and exocyclic nitrogen
pseudoamides are reported as well as examples of the normal-pseudoanhydride and
the dipseudoanhydride.
PMID- 9658556
TI - Localization of the proenzyme form of the vitellin-processing protease in
Blattella germanica by affinity-purified antibodies.
AB - During Blattella germanica embryo development, the nutritive yolk protein
vitellin is processed by a cysteine protease, which is activated proteolytically
from a proprotease during acidification of yolk granules. A murine polyclonal
antiserum was generated with the purified proprotease as the immunogen. The
antiserum was made monospecific to proprotease by subtractive affinity
chromatography using proprotease-free yolk proteins as ligand. The purified
antibodies were employed to investigate the temporal and spatial expression of
the proprotease during vitellogenesis and embryo development. Anti-proprotease
reactive peptides appeared in extracts of fat bodies and ovarian follicles of
post-mating females, but not in fat bodies of males or the fat bodies or
follicles of unmated females, suggesting that the proprotease is synthesized
extraovarially. Use of the antibodies was extended to monitor the kinetics of
proprotease disappearance during early embryo development.
PMID- 9658557
TI - Hemagglutinating properties of apolipophorin III from the hemolymph of Galleria
mellonella larvae.
AB - In search for factors that cause encapsulation of foreign bodies in insect
hemolymph we discovered that larval hemolymph of Galleria mellonella caused
aggregation of mammalian erythrocytes. The hemagglutinating agent was identified
as an 18-kDa protein that did not react with lectins. The sequence of 81 amino
acids in three protein fragments and the properties of the protein revealed that
it was Galleria homologue of apolipophorin III (apoLp-III). ApoLp-III was found
in high amounts in the hemolymph of Galleria larvae, pupae, and adults, as well
as in the molting fluid. The hemagglutinating action of the whole hemolymph or
the purified apoLp-III was independent of the presence of sugars in the medium.
This indicated that it was not mediated by carbohydrates on the erythrocyte
surface. The hemagglutination was inhibited at low pH (3.0), in the absence of
calcium ions, and in the presence of certain bacterial lipopolysaccharides or
their essential component, the 2-keto-3-deoxyoctonate-3-deoxyoctulosonic acid
(KDO). It is suggested that interaction of apoLp-III with lipopolysaccharides in
bacterial cell walls may play a role in insect immune reactions.
PMID- 9658558
TI - Actions of the pyrethroid insecticides cismethrin and cypermethrin on house fly
Vssc1 sodium channels expressed in Xenopus oocytes.
AB - Voltage-sensitive sodium channels encoded by the Vssc1 gene of the house fly
(Musca domestica) were expressed in Xenopus laevis oocytes in combination with
the tipE gene product of Drosophila melanogaster and were characterized by two
electrode voltage clamp. Vssc1/tipE sodium channels expressed in oocytes were
highly sensitive to tetrodotoxin; half-maximal inhibition of sodium currents by
tetrodotoxin was obtained at a concentration of 2.4 nM. Cismethrin, a pyrethroid
that produces Type I effects on intact nerve, slowed the inactivation of sodium
currents carried by Vssc1/tipE channels during a depolarizing pulse and induced a
tail current after repolarization that decayed with a first-order time constant
of approximately 650 ms. The voltage dependence of activation and steady-state
inactivation of cismethrin-modified channels were shifted to more negative
potentials. Cypermethrin, a pyrethroid with Type II effects on intact nerve, also
prolonged the inactivation of Vssc1/tipE sodium channels and induced a tail
current. However, the cypermethrin-induced tail current was extremely persistent,
decaying with a first-order time constant of approximately 42 s. Unlike
cismethrin, the effect of cypermethrin was use dependent, requiring repeated
depolarizing pulses for the full development of modified sodium currents. The
divergent effects of cismethrin and cypermethrin on Vssc1/tipE sodium channels
expressed in oocytes are consistent with the actions of these and related
compounds on sodium channels in invertebrate and vertebrate nerve preparations
and provide insight into the mechanisms underlying the production of Type I and
II effects on neuronal excitability.
PMID- 9658559
TI - Isolation and sequence of a partial vitellogenin cDNA from the cockroach,
Blattella germanica (L.) (Dictyoptera, Blattellidae), and characterization of the
vitellogenin gene expression.
AB - A partial cDNA clone of the vitellogenin gene from the cockroach Blattella
germanica has been isolated from a cDNA expression library using an anti-vitellin
vitellogenin antiserum probe. The analysis of cDNA inserts gave a sequence of
2,645 nucleotides corresponding to the 3' region. The deduced amino acid sequence
is 825 residues long and is similar to the homologous portion of the vitellogenin
of other insect species, especially that of the mosquito Aedes aegypti. RNA
hybridization studies indicated that the vitellogenin gene expression is limited
to the fat body of adult females. The pattern of expression during the first
vitellogenic cycle was approximately parallel to that of vitellogenin production
by the fat body previously described. The availability of a cDNA probe for the B.
germanica vitellogenin gene represents a useful tool to study the molecular
action of hormones affecting vitellogenin synthesis in this species.
PMID- 9658560
TI - Effect of culture medium on the in vitro secretion activity of prothoracic glands
from Pseudaletia separata.
AB - The prothoracic glands (PGs) taken from the last instar of the common armyworm,
Pseudaletia separata, were cultured in various media for the purpose of finding a
suitable medium for relatively long-term culture of PGs. Among the tested culture
media, MGM-450 medium without serum was the best to maintain PG cells viable for
relatively long periods, and to continue to secrete ecdysteroids. Secretion of
ecdysteroid by the PG in vitro became marked when the PG was taken from last
instar larvae older than 2 days after the last molt. PGs cultured in any of the
media secreted ecdysteroid only within the first 2 h after placing them in
culture, however, in the MGM-450 medium, the PGs secreted ecdysteroid even after
5 days of culture.
PMID- 9658561
TI - The response to domestic violence in a model court: some initial findings and
implications.
AB - This study utilized a non-experimental design to obtain information on a full
range of domestic violence incidents brought before the Quincy, Massachusetts
District Court, a model court. One limitation of previous research on spouse
assaults using more sophisticated designs is that the target population has been
restricted to specific subgroups of cases thereby limiting subsequent discussions
of policy/practice implications of the findings vis-a-vis all spouse assault
cases. To address this research "shortfall", we obtained permission from the
Quincy District Court to examine all the spouse assault cases brought before the
court during a 7-month period (June, 1995, through February, 1996). The findings
show that in a full enforcement environment, victims took out restraining orders
only against the most violent, criminally abusive men. Most men who were arrested
for domestic violence had prior criminal histories for a variety of offenses.
Domestic violence offenders appeared to be of two types: those with extensive and
diverse criminal histories and those with little or no such involvement. However,
active criminal justice intervention against domestic violence offenders appears
to be primarily directed toward offenders already active in the criminal justice
system.
PMID- 9658562
TI - The description of gay and lesbian families in second-parent adoption cases.
AB - Lesbians and gay men are turning to the courts to recognize their family
relationships. In this article every reported court decision where a lesbian or
gay couple has successfully completed a second-parent adoption is reviewed to
analyze the presentation and judicial analysis of the petitioning parties in
conjunction with the current debates within family theory. Traditional family
theorists argue that the contemporary family is in transition but will always be
recognizable as the traditional family; postmodern theorists argue that the
traditional "family" is a fiction. Results from this study indicate that judges
in second-parent adoption cases rely on a traditional definition and vision of
the family in evaluating the gay and lesbian petitioners before them.
PMID- 9658563
TI - Emotional maltreatment in adolescents' everyday lives: furthering sociolegal
reforms and social service provisions.
AB - The article examines sociolegal responses to adolescent victimization,
particularly responses to the emotional dimensions of their violent personal
relationships. The investigation reveals how the legal system generally fails to
recognize youth's emotional maltreatment. Responses tend to consider emotional
maltreatment as subordinate and secondary to some legally prohibited sexual and
physical assaults. Rather than casting emotional dimensions as ancillary to a
narrowly delimited set of sexual and physical assaults, this article proposes
that efforts to counter emotional maltreatment become the centerpiece of efforts
to understand adolescents' violent relationships; that it become central in the
design of policies aimed to foster adolescent development; and that no existing
legal rules or policy considerations prevent further recognition of adolescents'
legal right to protection from emotional maltreatment.
PMID- 9658564
TI - New enzymatic synthesis of 6(3)-modified maltooligosaccharides and their
inhibitory activities for human alpha-amylases.
AB - Ten new 6(3)-modified maltopentaoses and tetraoses were synthesized by enzymatic
reactions utilizing cyclodextrin glycosyltransferase (EC 2.4.1.19) and subsequent
human salivary alpha-amylase (HSA) (EC 3.2.1.1). Among these compounds, alpha-D
glucopyranosyl-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-(6-deoxy-alpha-D
glucopyranosyl)-(1-->4)- alpha-D-glucopyranosyl-(1-->4)-D-glucopyranose (11) and
alpha-D-glucopyranosyl-(1-->4)-(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)- alpha-D
glucopyranosyl-(1-->4)-D-glucopyranose (12) showed strong inhibitory activities
for human pancreatic alpha-amylase (HPA) and HSA. The IC50 of 6(3)
deoxymaltopentaose 11 (8.0 x 10(-5) M for HPA, 1.0 x 10(-4) M for HSA) and 6(3)
deoxymaltotetraose 12 (2.0 x 10(-3) M for HPA, 2.0 x 10(-3) M for HSA) were lower
than that of 6(3)-deoxymaltotriose [(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)
alpha-D- glucopyranosyl-(1-->4)-D-glucopyranose 13; 2.0 x 10(-3) M for HPA, 4.2 x
10(-2) M for HSA].
PMID- 9658565
TI - The synthesis of neoglycophospholipid conjugates via reductive amination of omega
oxoalkylglycosides and phosphatidylethanolamines.
AB - Phospholipid conjugates of mono- and disaccharides tethered with an n-decanyl
spacer were efficiently synthesized via an improved reductive amination of
deprotected omega-oxodecanyl beta-glycosides and phosphatidylethanolamines with
or without alkenyl groups. The omega-oxodecanyl beta-glycosides were prepared by
stereoselective glycosidation of glycosyl halides with 1, 10-decanediol followed
by pyridinium dichromate oxidation. The acetyl groups of the omega-oxodecanyl
beta-glycosides were removed with sodium methoxide prior to their conjugation
with phosphatidylethanolamines.
PMID- 9658566
TI - Synthesis of alpha-glucosidase inhibitors: kojibiose-type pseudo-disaccharides
and a related pseudotrisaccharide.
AB - Two kojibiose-type pseudo-disaccharides and a trisaccharide, containing a 5-amino
1,2,3,4-cyclopentanetetrol derivative or valienamine, linked by way of nitrogen
bridges to the sugar residues, have been designed and synthesized as processing
alpha-glucosidase I inhibitors. Synthesis of the pseudo-disaccharides was carried
out starting from the coupling products of the sugar isothiocyanates and an
aminocyclitol, respectively, by cyclization with mercury(II) oxide to the cyclic
isoureas and subsequent deprotection. Pseudokojibiose was prepared in a poor
yield by reaction of a protected valienamine and a sugar epoxide, followed by
deprotection. Although the pseudooligosaccharides are all strong inhibitors of
alpha-glucosidase (baker's yeast), they did not have any inhibitory potency
against either sucrase isomaltase (rat intestine) or processing alpha-glucosidase
(rat liver microsomes).
PMID- 9658567
TI - The structure of the exocellular polysaccharide from the cyanobacterium
Cyanospira capsulata.
AB - The exocellular polysaccharide produced by the cyanobacterium Cyanospira
capsulata has been subjected to partial acid hydrolysis and N-deacetylation
nitrous acid deamination. The oligosaccharides released have been isolated by
weak anion exchange and aqueous size exclusion chromatography, and characterized
by a combination of 1D and 2D nuclear magnetic resonance spectroscopy, mass
spectrometry, sugar composition and linkage analyses. The polysaccharide has an
octasaccharide repeating unit with the following structure: [formula: see text]
PMID- 9658568
TI - Structural analysis of the exopolysaccharides produced by Lactobacillus spp. G
77.
AB - The exopolysaccharide produced by a ropy strain of Lactobacillus spp. G-77 in a
semi-defined medium, was found to be a mixture of two homopolymers composed of D
Glc. The two poly-saccharides were separated and, on the basis of monosaccharide
and methylation analyses, 1H, 13C, 1D and 2D NMR experiments, one of the
polysaccharides was shown to be a 2-substituted-(1-3)-beta-D-glucan, identical to
that described for the EPS from Pediococcus damnosus 2.6 (M.T. Duenas-Chasco,
M.A. Rodriguez-Carvajal, P. Tejero-Mateo, G. Franco-Rodriguez, J. L. Espartero,
A. Irastorza-Iribar, and A.M. Gil-Serrano, Carbohydr. Res., 303 (1997) 453-458),
and the other polysaccharide was shown to consist of repeating units with the
following structure [formula: see text]
PMID- 9658569
TI - Glycosphingolipids of skeletal muscle: I. Subcellular distribution of neutral
glycosphingolipids and gangliosides in rabbit skeletal muscle.
AB - Membrane vesicles were prepared from rabbit skeletal muscle, separated by sucrose
density gradient centrifugation and characterized by their specific marker
enzymes, ligand binding, and ion flux activities. The fractions obtained (in the
order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic
reticulum (SR1 and SR2) and triads/mitochondria (Tr/M). Their glycosphingolipid
compositions were analyzed by biochemical and immunochemical methods with
specific antibodies (TLC immunostaining) and characteristic patterns were
obtained from respective membrane fractions, expressed on a protein basis.
Glucosylceramide, the main neutral glycosphingolipid of rabbit muscle, was found
in SL and TT fractions, whereas SR and Tr/M vesicles lack this compound.
Lactosylceramide was selectively recovered in the SR1 fraction. GM3(Neu5Ac), the
main ganglioside in rabbit muscle, was found to account for 64% in the SL, 13% in
the TT, 7% in the SR1, 3% in the SR2 and 13% in the Tr/M fractions. IV3Neu5Ac
nLcOse4Cer was mostly abundant in SL and decreased in the order SL > TT, Tr/M >
SR1, SR2. IV6Neu5Ac-nLcOse4Cer was only detected in the SL and Tr/M fractions in
noteworthy quantities. Ganglioseries gangliosides GM1, GD1a, GD1b and GT1b
displayed homogeneous distribution patterns in each membrane preparation. They
were expressed only in small amounts but mainly in SL, TT and Tr/M vesicles and
to less extent in SR1 and SR2 fractions. The presence of GM3(Neu5Ac) in the SL as
well as on subcellular level was confirmed in transverse muscle cryosections by
means of indirect immunofluorescence microscopy. The SL was brightly stained, but
considerable intracellular fluorescence was observed as expected from the
biochemical analyses. Thus, the neutral GSL and ganglioside expression of the SL
and the intracellular membraneous network is different in skeletal muscle both in
terms of quantitative and qualitative GSL composition as demonstrated in details
by means of biochemical and immunochemical techniques. The modulatory functions
of GM3 and gangliosides of the neolacto- and ganglio-series towards the voltage
dependent Ca(2+)-channel, largely preponderant in the triads-containing Tr/M
fraction, is the subject of the accompanying paper (J. Muthing, U. Maurer, and S.
Weber-Schurholz, Carbohydr. Res., 307 (1998) 147-157).
PMID- 9658570
TI - Glycosphingolipids of skeletal muscle: II. Modulation of Ca2(+)-flux in triad
membranes by gangliosides.
AB - Membrane vesicles of rabbit skeletal muscle were prepared and separated by
sucrose density gradient centrifugation. The fractions obtained (in the order of
increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic reticulum
(SR1 and SR2) and triads/mitochondria (Tr/M) as characterized by their specific
marker enzymes, ligand binding, and ion flux activities. The distribution of
neutral glycosphingolipids and gangliosides in these membrane preparations has
been documented in the preceding paper (J. Muthing, U. Maurer, U. Neumann, B.
Kniep, and S. Weber-Schurholz, Carbohydr, Res., (1988) 135-145). GM3(Neu5Ac) is
the dominant ganglioside, neolacto-series gangliosides are moderately expressed
and ganglio-series gangliosides were found in minor quantities, however, all
showing different qualitative and quantitative membrane-type specific patterns.
The voltage dependent Ca(2+)-channels of skeletal muscle reside prevalently in
the triad enriched membrane fractions deduced from highest binding capacity of
1,4-dihydropyridines. Calcium channel complexes of triads were reconstituted into
unilamellar phospholipid vesicles of 400 nm defined size and the active 45Ca(2+)
uptake into intravesicular space was measured after incorporation of muscle
specific gangliosides into the outer vesicle lipid bilayer in parallel to control
liposomes without gangliosides. GM3(Neu5Ac) strongly increased the uptake of
45Ca2+ (+285%) whereas GM3(Neu5Gc) severely inhibited the ion flux (-61%).
Neolacto-series gangliosides evoked miscellaneous effects upon 45Ca(2+)-flux
depending on isomeric sialic acid configuration, oligosaccharide size and fatty
acid chain length of the ceramide portion. VI3Neu5Ac-nLcOse6Cer (C24-fatty acid),
IV3Neu5Ac-nLcOse4Cer (C16-fatty acid) and IV6Neu5Ac-nLcOse4Cer (C16-fatty acid)
strongly enhanced the 45Ca(2+)-flux (+208, +162, and +120%, respectively, whereas
IV3Neu5Ac-nLcOse4Cer (C24-fatty acid), VI3Neu5Ac-nLcOse6Cer (C16-fatty acid) and
IV6Neu5Ac-nLcOse4Cer (C24-fatty acid) slightly reduced 45Ca(2+)-flux (-3, -6, and
-17%, respectively). Out of all gangliosides tested in this study, GM1 showed the
strongest stimulatory effect (+327%). GD1a and GT1b gave rise to remarkable flux
stimulation of +283 and +255%, respectively, whereas GD1b exhibited only a
slightly positive effect (+38%). This data suggest a functional role of
gangliosides in subcellular muscle membranes giving strong evidence that
gangliosides are capable of modulating the cytosolic calcium level of muscle,
which regulates muscle contraction.
PMID- 9658571
TI - Reinvestigation of the O-specific polysaccharides of Hafnia alvei
lipopolysaccharides isolated from strains ATCC 13337 and 1187.
AB - The structure of the O-specific polysaccharides of the lipopolysaccharides
produced by Hafnia alvei strains ATCC 13337 and 1187 was reinvestigated. The
position of phosphate group in the repeating units of the polysaccharides was
established with the aid of 1H detected, 31P edited NMR spectra. According to the
results obtained, the polysaccharides are teichoic acid-like polymers with the
repeating units of the following structure: [formula: see text] where Acyl = D-3
hydroxylbutyryl, and 3-O-acetylation was approximately 30%.
PMID- 9658572
TI - Structural analysis of the intact polysaccharide mannan from Saccharomyces
cerevisiae yeast using 1H and 13C NMR spectroscopy at 750 MHz.
AB - The mannan from Saccharomyces cerevisiae yeast was studied by high field NMR
spectroscopy in an attempt to deduce the structure of the polysaccharide and to
assess the ratio of different side chains. The results show that all structural
information, agreeing with previously published data, can be extracted by
analysis of the NMR spectra of the intact and modified mannan.
PMID- 9658573
TI - Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of
gastrin/cholecystokinin-B receptors. II.
AB - A series of phenoxyacetanilide derivatives was synthesized and their antagonist
activities for human gastrin/cholecystokinin (CCK)-B and CCK-A receptors were
evaluated. Among the compounds synthesized, 2-[3-[3-[N-[2-(N-methyl-N
phenylcarbamoylmethoxy)phenyl]-N-(N-meth yl-N-
phenylcarbamoylmethyl)carbamoylmethyl]-ureido]phenyl]acetic acid (20i, DA-3934)
exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK
A receptors. DA-3934 and its methyl ester derivative inhibited pentagastrin
induced gastric acid secretion in rats in a dose-dependent manner.
PMID- 9658574
TI - alpha-Methylene-gamma-butyrolactones: synthesis and vasorelaxing activity assay
of coumarin, naphthalene, and quinoline derivatives.
AB - Certain alpha-methylene-gamma-butyrolactone derivatives of coumarin, naphthalene,
and quinoline were synthesized and evaluated for vasorelaxing effects on isolated
rat thoracic aorta. The 7-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2
furanyl)methoxy]-2H- 1- benzopyran-2-ones, which have an aliphatic methyl
substituent at the lactone C2, were more active than their C2-phenyl counterparts
against high-K+ (80 mM) medium, Ca2+ (1.9 mM)-induced vasoconstriction and the
norepinephrine (NE, 3 microM)-induced phasic and tonic constrictions (2a vs. 2b;
2c vs. 2d; 2e vs. 2f; 2g vs. 2h). Although 3-chloro-7-[(2,3,4,5-tetrahydro-2
methyl-4-methylene-5-oxo-2- furanyl)methoxy]-4-methyl-2H-1-benzopyran-2-one (2g)
demonstrated the most potent inhibitory activities on the NE-induced phasic and
tonic constrictions at concentrations of as low as 10 micrograms/ml, it possesses
both affinity for NE-receptor and intrinsic activity to trigger the
vasoconstriction. However, 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylene-5-oxo-2-
furanyl)methoxy]quinoline (10a) and other quinoline derivatives (11a, 12a) are
pure irreversible non-competitive blockers of NE-receptor with no intrinsic
activity. The aromatic ring played an important role in the vasorelaxing effects
of alpha-methylene-gamma-butyrolactones; naphthalene was inactive, quinolines
exhibited only affinity to the alpha-receptor, and coumarins possessed both
affinity and intrinsic activity.
PMID- 9658575
TI - Studies on 5-lipoxygenase inhibitors. I. Synthesis and 5-lipoxygenase-inhibitory
activity of novel hydroxamic acid derivatives.
AB - A series of novel hydroxamates has been prepared and tested for inhibitory
activity towards rat polymorphonuclear leukocyte (PMN) 5-lipoxygenase (5-LO) in
vitro and towards neutrophil migration in the rat air pouch model of inflammation
in vivo. Many 3,4-dihydronaphthyl compounds were potent inhibitors of 5-LO, and
several compounds were potent inhibitors of neutrophil migration. The most potent
3,4-dihydronaphthyl compound, N-[[(3,4-dihydro-5-phenoxy)-2-naphthyl]methyl]-N
hydroxy-N'-ethylurea (FR122788, 18) had an IC50 of 25 nM in the 5-LO assay, and
strongly reduced neutrophil migration in the rat air pouch model at 1 mg/kg
(p.o.). FR122788 also had an ameliorating effect in a rat hepatitis model induced
by D-galactosamine, with an ED50 values of 14.6 mg/kg (p.o.) for glutamate
oxaloacetate transaminase (GOT) and 16.8 mg/kg (p.o.) for glutamate pyruvate
transaminase (GPT).
PMID- 9658576
TI - Studies on nonpeptide angiotensin II receptor antagonists. IV. Synthesis and
biological evaluation of 4-acrylamide-1H-imidazole derivatives.
AB - A novel series of nonpeptide angiotensin II antagonists containing the acrylamide
group at the 4-position of the imidazole ring was synthesized and their
antagonistic activity was examined by functional assay in rabbit aorta. The
acrylamide group was selected as a large lipophilic surrogate for the chloro
group of EXP3174. A structure-activity relationship study of the acrylamide
moiety has shown that substitution at the 4-position with the N-methyl-3,3
dimethylacrylamide group resulted in the optimal compound, 2-butyl-4-[(3,3
dimethylacryloyl)methyl-amino]-1-[[2'-(1H-tetra zol-5- yl)biphenyl-4-yl]methyl]
1H-imidazole-5-carboxylic acid (1), which was superior to EXP3174 in vitro. Since
1 showed only poor activity against angiotensin II-induced pressor response in
rats after oral administration, the carboxylic acid function of 1 was converted
into prodrug esters (13). Among these, the 1-[(ethoxycarbonyl)oxy]ethyl ester
(13a) showed the most potent and longest-lasting activity when given orally to
rats. When administered orally to conscious furosemide-treated dogs, 13a showed
an approximately 3-fold increased hypotensive activity in comparison with DuP
753. These data suggest that 13a may be an useful agent for the treatment of
angiotensin II-dependent diseases, such as hypertension.
PMID- 9658577
TI - Medicinal foodstuffs. XIV. On the bioactive constituents of moroheiya. (2): New
fatty acids, corchorifatty acids A, B, C, D, E, and F, from the leaves of
Corchorus olitorius L. (Tiliaceae): structures and inhibitory effect on NO
production in mouse peritoneal macrophages.
AB - Following the characterization of the glycosidic constituents in a medical
foodstuff "moroheiya," the leaves of Corchorus olitorius L., four higher fatty
acids with a trienone function, corchorifatty acids, A, B, C, and D, an
undecanoic acid, corchorifatty acid E, and a trihydroxyfatty acid, corchorifatty
acid F, were isolated from the less polar fraction of "moroheiya". The structures
and optical purity of corchorifatty acids were determined on the basis of
chemical and physicochemical evidence. Corchorifatty acids A, B, and C showed an
inhibitory effect on lipopolysaccharide-induced NO production in cultured mouse
peritoneal macrophages.
PMID- 9658578
TI - Serotonin 5-HT4 receptor agonistic activity of the optical isomers of (+/-)-4
amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3- dihydro-2
methylbenzo[b]furan-7-carboxamide.
AB - The enantiomers, (R)-(-)-1 and (S)-(+)-1, of (+/-)-4-amino-N-[2-(1
azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3- dihydro-2-methylbenzo[b]furan-7
carboxamide [(+/-)-1] were prepared from optically active benzyl 4-acetylamino
2,3-dihydro-2-methylbenzo[b]furan-7-carboxylate [(R)-(+)-6, (S)-(-)-6],
respectively. The requisite (R)-(+)-6 and (S)-(-)-6 were prepared by large-scale
preparative HPLC on chiral stationary phases (CSPs). The absolute configuration
of (S)-(+)-1 was determined by single crystal X-ray analysis. The serotonin 5-HT4
receptor agonistic activity of (S)-(-)-1 hemifumarate (SK-951) which was
hemifumarate of (S)-(+)-1 was about twice that of the other enantiomer (R)-(+)-1
hemifumarate which was hemifumarate of (R)-(-)-1.
PMID- 9658579
TI - Studies on the constituents of Broussonetia species. III. Two new pyrrolidine
alkaloids, broussonetines G and H, as inhibitors of glycosidase, from
Broussonetia kazinoki Sieb.
AB - Two new pyrrolidine alkaloids, broussonetines G and H, were isolated from the
branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines G and H were
formulated as 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy-
6:10;10:13-diepoxytridecyl)-pyrrolidine (1) and 2 beta-hydroxymethyl-3 alpha, 4
beta-dihydroxy-5 alpha-(1-hydroxy- 5:9;9:13-diepoxytridecyl)-pyrrolidine (2),
respectively, by spectroscopic methods. 1 and 2 inhibited beta-glucosidase, beta
galactosidase and beta-mannosidase.
PMID- 9658581
TI - Receptor binding thermodynamics as a tool for linking drug efficacy and affinity.
AB - Determination of drug-receptor binding constants (association, KA, or
dissociation, KD = l/KA) by radiochemical specific binding assays has proved to
be an invaluable tool for screening of potential active drugs. Simple
determination of KA (or KD) values makes it possible, however, to calculate the
standard free energy delta G degree = -RTln KA = RTln KD (T = 298.15 K) of the
binding equilibrium but not that of its two components as defined by the Gibbs
equation delta G degree = delta H degree - T delta S degree, where delta H degree
and delta S degree are the equilibrium standard enthalpy and entropy,
respectively. This incomplete knowledge is highly inconvenient from a pure
thermodynamic point of view as delta H degree and delta S degree carry much
information on the details of the drug-receptor interaction and the interplay of
both reaction partners with the solvent. In recent times it has been shown that
the relative delta H degree and delta S degree magnitudes can often give a simple
'in vitro' way for discriminating 'the effect', that is the manner in which the
drug interferes with the signal transduction pathways. This particular effect,
called 'thermodynamic discrimination', results from the fact that binding of
antagonists may be enthalpy-driven and that of agonists entropy-driven, or vice
versa. The first case of thermodynamic discrimination was reported for the beta
adrenergic G-protein coupled receptor (GPCR) and only recently has it been
confirmed for adenosine A1 and A2a receptors. Only very recently has the binding
thermodynamics of ligand-gated ion channel receptors (LGICR) been investigated
and data for four receptors have been reported showing that all of them are
thermodynamically discriminated. While it seems difficult at present to find a
reasonable explanation for the thermodynamic discrimination phenomenon in GPCR,
some hypotheses can be suggested for LGICR. Since global delta H degree and delta
S degree values of the binding process are expected to be heavily affected by
rearrangements occurring in the solvent, thermodynamic discrimination in LGICR is
at least logically understandable admitting that the observed delta H degree (and
then delta S degree) values are determined by both specific binding and abrupt
variation of water-accessible receptor surfaces consequent to the setting up of
the channel opening.
PMID- 9658582
TI - Modulation of glutamate receptor pathways in the search for new neuroprotective
agents.
AB - Excessive stimulation of excitatory amino acid (EAA) receptors is responsible for
a wide variety of acute and chronic neurological impairments. A separate line of
investigation has focused on oxidative stress as one of the main reasons for
several of these degenerative disorders. Current evidence has confirmed that
activation of both ionotropic and metabotropic glutamate receptors can also
result in either neuroprotection or neurodegeneration according to the role
played by oxidative stress mechanisms. An outline of this research, together with
our recent results aimed at the discovery of new subtype selective modulators of
the central nervous system pathways as well as new classes of free radical
scavengers, is presented.
PMID- 9658583
TI - Obesity genes: molecular genetic approaches to drug target identification.
AB - The environment for developing novel therapeutic agents has undergone dramatic
change over the past decade. Innovative strategies for identifying and utilizing
molecular targets linked to particular human diseases are replacing the classic
approach of screening chemical compounds for potential therapeutic action on
unknown targets. Since genetic components are involved in many known diseases,
mouse and human genetics, positional cloning and other molecular biology-based
approaches are now used to identify genes that are associated with these
diseases. It is thought that identification of these disease-linked genes may
lead to the discovery and understanding of the physiologically relevant
biochemical pathways underlying the disease processes. Clearly, a knowledge of
these biochemical pathways will provide future molecular targets, enzymes or
receptors, that will offer opportunities to apply modern methods of high
throughput screening, medicinal chemistry, parallel synthesis and combinatorial
chemistry for drug discovery. In this manuscript, we illustrate how mouse
genetics and molecular biology-based approaches have led to the identification of
all five known single gene mutations that cause obesity in mice. Additionally, we
describe how identification of these genes has helped unravel underlying
biochemical pathways that regulate behavioral, metabolic and neuroendocrine
responses in rodents.
PMID- 9658584
TI - Csk-mediated phosphorylation of substrates is regulated by substrate tyrosine
phosphorylation.
AB - Csk is a cellular protein tyrosine kinase (PTK) that has been shown to
specifically regulate the activity of Src kinase family members by
phosphorylation of a carboxy-terminal tyrosine residue. The molecular mechanisms
controlling Csk regulation and its substrate specificity have not been
elucidated. Here we report a novel type of overlay kinase assay that allows to
probe for Csk-mediated phosphorylation of cellular substrates separated by
polyacrylamide gel electrophoresis and transferred to nitrocellulose filters.
Most of the cell lines analyzed with this method revealed only a few potential
Csk substrates. However, an increased number of Csk substrates was detected in
NIH3T3 cells expressing a constitutively activated form of the Src kinase Lck or
in PC12 and NIH3T3 cells that had been treated with pervanadate. These cells all
display an increased level of cellular protein tyrosine phosphorylation which led
to the conclusion that Csk preferentially phosphorylates tyrosine-phosphorylated
proteins. To verify this hypothesis we analyzed Csk-mediated phosphorylation of
recombinant Lck, a known Csk substrate. Results demonstrated that
autophosphorylation of Lck (at Tyr394) facilitates Csk-mediated phosphorylation
of Lck at its regulatory site (Tyr505). Subsequent peptide binding studies
revealed that Csk can bind to a peptide corresponding to the Lck
autophosphorylation site only when it is phosphorylated. These findings suggest
that autophosphorylation of Lck at Tyr394 triggers an interaction with Csk and
thereby facilitates subsequent phosphorylation and inactivation of Lck. The
phosphorylation of other cellular Csk substrates may be regulated by a similar
mechanism.
PMID- 9658585
TI - Molecular mechanisms involved in the activation and regulation of the alpha 1
adrenergic receptor subtypes.
AB - The adrenergic receptors (ARs) belong to the superfamily of membrane-bound G
protein coupled receptors (GPCRs). Our investigation has focused on the structure
function relationship of the alpha 1b-AR subtype used as the model system for
other GPCRs. Site-directed mutagenesis studies have elucidated the structural
domains of the alpha 1b-AR involved in ligand binding, G protein coupling or
desensitization. In addition, a combined approach using site-directed mutagenesis
and molecular dynamics analysis of the alpha 1b-AR has provided information about
the potential mechanisms underlying the activation process of the receptor, i.e.
its transition from the 'inactive' to the 'active' conformation.
PMID- 9658586
TI - Search for selective antagonists at alpha 1-adrenoreceptors: neutral or negative
antagonism?
AB - In this article the use of competitive antagonists as tools in receptor
characterization and classification is discussed. It is pointed out that caution
is required in receptor characterization because negative antagonism (inverse
agonism) rather than neutral antagonism could play a relevant role. This implies
that antagonists should be evaluated not only with regard to their affinity, but
also with regard to their ability to affect the equilibrium between the two
receptor states, namely active and inactive states. Since affinity and efficacy
of a negative antagonist are system dependent the use of negative antagonists as
competitive antagonists in receptor characterization may give rise to false
differences in receptor subtypes. Finally, this article summarizes recent
developments in the design of new alpha 1-adrenoreceptor antagonists which are
structurally related to prazosin or WB 4101.
PMID- 9658587
TI - Molecular toxicology and the medicinal chemist.
AB - Drug metabolism has a number of pharmacodynamic and pharmacokinetic consequences
which cannot be ignored even at the early stages of drug research. A number of
aspects of drug metabolism are thus of interest to medicinal chemists, e.g.
prodrug and soft drug design. This mini-review focuses mainly on toxication
resulting from reactions of functionalization and conjugation. In the former
case, oxidoreductases can reduce xenobiotics to nucleophilic radicals, or oxidize
them to electrophilic and oxidizable metabolites. Conjugation reactions also play
a role in toxication by generating lipophilic residues (e.g. hybrid
triglycerides) or adduct-forming metabolites (e.g. some acylglucuronides), or by
interfering with physiological pathways (e.g. Coenzyme A conjugates). Functional
moieties undergoing such reactions are known as toxophoric groups. Because they
are the biochemical endpoint of several toxication reactions, macromolecular
adducts are now of special significance in molecular toxicology. But, as
discussed in the conclusion, the substrate specificity of drug-metabolizing
enzymes, the many biological factors that influence metabolism, and various
repair and removal mechanisms all contribute to decrease toxicological risks and
to protect organisms.
PMID- 9658588
TI - Synthesis and antihypertensive activity of 2,4-dioxoimidazolidin-1-yl and
perhydro-2,4-dioxopyrimidin-1-yl ergoline derivatives.
AB - The synthesis and antihypertensive activity of a series of 2,4-dioxoimidazolidin
1-yl and perhydro-2,4-dioxopyrimidin-1-yl ergoline derivatives are reported. The
oral antihypertensive activity was studied in spontaneously hypertensive rats
(SHRs) by measuring systolic blood pressure by an indirect tail-cuff method at
different times after treatment. The prolactin lowering activity (indirectly
measured by the nidation test) in rats and the oral acute toxicity in mice were
also studied. The results of this study revealed potent antihypertensive ergoline
derivatives devoid of side-effects related to the dopaminergic stimulation and
the importance of the delta 9,10 double bond for conferring high potency within
these compounds.
PMID- 9658589
TI - 1,2,3-Triazolo[1,5-a][1,4]- and 1,2,3-triazolo[1,5-a]-[1,5]benzodiazepine
derivatives: synthesis and benzodiazepine receptor binding.
AB - This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and
1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward
benzodiazepine receptors. Receptor affinity gradually and remarkably increases by
moving the nitrogen atom of the central ring from position 3 through 4 to
position 5, to give the most effective compound 6a (Ki = 150 nM). N-methylation
of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine
atom on the benzene ring doubles the Ki value (6b) which remains unaltered by the
N-methylation (7b).
PMID- 9658590
TI - Comparison of three histological fixatives on the immunoreactivity of mammalian P
glycoprotein antibodies in the sheepshead minnow, Cyprinodon variegatus.
AB - Mammalian P-glycoprotein is a highly conserved integral membrane protein
functioning as an energy-dependent efflux pump which decreases the concentration
of certain lipophilic aromatic compounds entering the cell by diffusion.
Expression of such a transporter in teleost species could play a significant role
in conferring resistance to fish populations exposed to xenobiotic stressors and
may serve as a potential indicator of species at risk for certain environmental
contaminants. In previous studies we demonstrated that a strong correlation
existed between corresponding mammalian and teleost tissues showing
immunoreactivity to specific mammalian P-glycoprotein antibodies. In the present
study, comparisons of staining pattern, intensity, and tissue specificity between
tissues treated in Bouin's, Dietrich's and Lillie's histological fixatives were
determined in the sheepshead minnow, Cyprinodon variegatus, using monoclonal
antibodies C219, C494, JSB-1 and polyclonal antiserum MDR(Ab-1). Immunoreactivity
of these antibodies was found to be fixative-dependent. Results are presented
illustrating the differential staining patterns and tissue specificity observed
for each tissue type, fixative, and antibody combination. Our data indicate
tissue fixation has a significant impact on P-glycoprotein antibody immuno
reactivity in teleost tissues and must be considered in the comparison and
interpretation of results.
PMID- 9658591
TI - Kinematics of aquatic and terrestrial prey capture in Terrapene carolina, with
implications for the evolution of feeding in cryptodire turtles.
AB - Studies of aquatic prey capture in vertebrates have demonstrated remarkable
convergence in kinematics between diverse vertebrate taxa. When feeding in water,
most vertebrates employ large-amplitude hyoid depression to expand the oral
cavity and suck in water along with the prey. In contrast, vertebrates feeding on
land exhibit little or no hyoid depression. In this study we compared the
kinematics of terrestrial and aquatic prey capture within one species of turtle,
Terrapene carolina, in order to determine whether an individual species can
modulate the magnitude of hyoid depression between air and water. High-speed
video (250 frames per second) showed that hyoid depression was over three times
greater in aquatic than in terrestrial feedings, indicating that T. carolina is
able to modulate hyoid depression magnitude depending on the medium in which
feeding occurs. In addition, we observed medium-dependent modulation of hyoid
depression in another turtle, Heosemys grandis, and large-amplitude hyoid
depression during aquatic feeding in Kinosternon leucostomum, Platysternon
megacephalum, and juvenile Chelydra serpentina. In all of these turtles, hyoid
depression produced oral cavity expansion during aquatic feeding, but the
earthworm prey were never sucked toward the predators. Prey were captured by neck
extension (ram feeding), and we conclude that the function of hyoid depression
during aquatic feeding in cryptodire turtles is to prevent the forward motion of
the predator from pushing the prey away (compensatory suction). Aquatic feeding
is probably the primitive condition for all extant turtles, and thus terrestrial
feeding in T. carolina and other turtles is a secondarily derived characteristic.
We conclude from this historical pattern that it is not appropriate to use extant
turtles in attempts to reconstruct the terrestrial feeding mechanisms of
primitive amniotes.
PMID- 9658592
TI - Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria
glaberrima Selenka (Holothuroidea:Echinodermata).
AB - Echinoderms are the deuterostome group with the most striking capacity to
regenerate lost body parts. In particular, members of the class Holothuroidea are
able to regenerate most of their internal organs following a typical evisceration
process. Such formation of new viscera in an adult organism provides a unique
model to study the process of organogenesis. We have studied this process in the
sea cucumber Holothuria glabberrima by describing the spatial and temporal
pattern of cellular events that occur during intestine regeneration following
chemically induced evisceration. Regeneration begins as a thickening of the
mesenteries that supported the autotomized organs to the body wall. The
mesenterial thickening consists of tissues where most of the cellular populations
found in the normal intestine are already present. However, the cell numbers
differ, particularly those of hemocytes and amoebocytes, suggesting that some of
these cells play an important role in the formation of the solid rod of
hypertrophic mesentery that characterizes the intestinal primordia. The
appearance of the luminal epithelium, together with the formation of the lumen,
occurs during the second week of regeneration by proliferation and extensive
migration of cells from the esophagus and cloacal ends into the thickenings. At
this stage all tissue layers are present, but it takes an additional week for
them to exhibit the proportions typical of the normal organ. Cell division, as
determined by BrdU labeling, mainly occurs in the coelomic epithelia of the
hypertrophic mesentery and in the regenerating luminal epithelium. Our study
provides evidence that the process of new organ formation in holothurians can be
described as an intermediate process showing characteristics of both epimorphic
and morphallactic phenomena.
PMID- 9658593
TI - Gradient in convergent cell movement during Fundulus gastrulation.
AB - This contribution represents a continuation of our studies of a gradient in
convergent cell movement in the germ ring (GR) during Fundulus gastrulation
(Trinkaus et al. [1992] J. Exp. Zool., 261:40-61). In our previous study, we
discovered that cells in the dorsal GR nearest the embryonic shield (ES) move
toward the ES at a net faster rate than those farther away and that this is due
to less meandering. Those farther away meander more. These data suggest the
hypothesis that there is a gradient of cues that direct cells to the ES. If so,
cells in the ventral GR, farthest from the ES, should meander even more and hence
show little or no convergence toward the ES. To test this hypothesis, we have
traced the trajectories of individual cells in the midventral GR during
midepiboly and have found that, although the general motile behavior of ventral
GR cells is the same as that of dorsal cells, they do indeed meander much more
and, as a result, show little or no directional movement toward the ES. Taken
together, these results indicate that cells of the germ ring move up a gradient
in directionality as they converge toward their target, the embryonic shield. One
possible explanation for this is that the embryonic shield attracts cells to
itself.
PMID- 9658594
TI - Hormonal and photoperiodic modulation of testicular mRNAs coding for
inhibin/activin subunits and follistatin in Clethrionomys glareolus, Schreber.
AB - Photoperiodic and hormonal modulation of mRNAs for testicular inhibin/activin
subunits and follistatin were studied in a seasonally breeding rodent, the bank
vole (Clethrionomys glareolus). Photoperiod-induced testicular regression had no
effect on the relatively low steady-state levels of follistatin mRNA. Inhibin
alpha (I alpha) and beta B (I beta B) mRNA levels were significantly higher in
regressed than in active gonads, but inhibin beta A was undetectable. The effect
of gonadotropin administration on testicular weight and mRNA concentrations
differed between the sexually active and quiescent voles. Neither FSH (1.2 U/kg;
s.c. for 5 days) nor hCG (600 IU/kg; s.c. for 5 days) affected testicular weight
in sexually active voles, whereas both gonadotropins significantly increased
testicular weight in photo-regressed individuals. FSH had no effect on I alpha or
I beta B mRNA concentrations in the active testes, whereas excessive hCG
challenge induced a decrease in the steady-state levels of these mRNAs. FSH
induced an increase in I alpha mRNA concentrations in the regressed gonad,
whereas both gonadotropins concomitantly down-regulated I beta B mRNA levels. In
conclusion, the high expression of I alpha and I beta B mRNA in the regressed
testis imply autocrine and paracrine roles for inhibin/activin in the quiescent
gonad of seasonal breeders. Inhibin alpha-subunit expression is at least partly
under the control of FSH in the bank vole testis.
PMID- 9658595
TI - Differential sensitivity of zonagenesis and vitellogenesis in Atlantic salmon
(Salmo salar L) to DDT pesticides.
AB - In Atlantic salmon (Salmo salar L) female sexual maturation entails both
zonagenesis and vitellogenesis, both of which are controlled by increasing levels
of estradiol-17 beta (E2). Antibodies against salmon zona radiata proteins
(eggshell zr-proteins) and vitellogenin were used to monitor induction of
oogenesis in juvenile salmon. Molecular weights of zr-monomers were estimated to
about 66, 61, and 55 kDa, and to about 180 kDa for vitellogenin. Xenobiotics such
as the pesticide DDT impair biological reproduction. The o,p'-DDT (1,1,1
trichloro-2[2-chlorophenyl]-2-[4-chlorophenyl]ethane) isomer seems to be a
xenoestrogen. Serum levels of zr-proteins and vitellogenin, and hepatocytic
biosynthesis of these components, were determined after in vivo treatment of
salmon with DDT (technical, p,p'-(1,1,1-trichloro-2,2-bis[4-chlorophenyl]ethane)
or o,p'-DDT) or E2. Exposing fish to frequent doses of o,p'-DDT (25 mg/kg b.w.
(body weight) twice a week, six times totally) resulted in induction of all three
zr-protein monomers, but not of vitellogenin. In contrast, three weekly injection
of 10 mg/kg b.w. of either of the three DDT preparations did not induce typical
zr-proteins or vitellogenin in serum. In vivo studies with combined DDT + E2
injections showed that none of the DDT preparations influenced E2-induced
biosynthesis of zr-proteins or vitellogenin. E2 induction of these oogenetic
processes was not blocked even by a high concentration (125 mg/kg b.w.) of o,p'
DDT. Furthermore, pretreatment of salmon with o,p'-DDT for 2 weeks, followed by
one injection of E2, did not antagonize biosynthesis of zr-proteins, but serum
concentration of vitellogenin was decreased. The data indicate that in juvenile
salmon o,p'-DDT may be xenoestrogenic with regard to zonagenesis, but weakly anti
(xeno)estrogenic with regard to vitellogenesis. These findings suggest new
complexities in fish reproductive toxicology of xenoestrogens. Compared to
vitellogenesis, zonagenesis is a more sensitive parameter for monitoring
reproductive effects of xenoestrogens.
PMID- 9658596
TI - Fulminant hepatic failure: is it a preventable syndrome?
PMID- 9658597
TI - Ultrasound-guided puncture of the gallbladder for acute cholecystitis.
AB - We performed a US-guided aspiration of the gallbladder in 27 patients with an
acute cholecystitis and severe concurrent disease, not responding to IV
antibiotics and supportive therapy. Twenty six of the 27 patients improved after
the procedure. One patient died 7 days after the procedure due to multi organ
failure; in the others immediate surgery could be avoided. Three patients
experienced local pain after the procedure; no other puncture related
complications were encountered. Long-term results (mean follow up 18 months;
range 2-36 months) were excellent in 20/26 survivors with no biliary
complications or need for elective cholecystectomy. Six of the 26 patients needed
subsequent cholecystectomy for relapse or incomplete cure.
PMID- 9658598
TI - Corticosteroid treatment in active Crohn's disease.
AB - Despite recent improvements in the management of Crohn's disease, steroids are
still the most efficacious treatment in flare ups of the disease. However they
have significant side effects and are only effective in the short term. There is
no consensus regarding initial dose or duration of corticotherapy. With 1 mg/Kg a
day of oral prednisolone given for 3 to 7 weeks, 92% of the patients achieve
clinical remission. Topical acting oral corticosteroids such as budesonide seem
to represent an important therapeutic advance due to their better tolerance. The
promising results of budesonide in mild and moderate flare ups need to be
confirmed and its indication in severe disease beside high dose prednisolone has
to be clarified.
PMID- 9658599
TI - Ultrasonically guided fine needle puncture of focal liver lesions. Review and
personal experience.
AB - Despite recent advances in diagnostic imaging of the liver, the management of a
patient with focal liver lesions often depends on obtaining tissue for
histological diagnosis. Ultrasound guided fine needle biopsy is recommended as a
safe and reliable method for cyto-histological confirmation of suspected hepatic
malignancy. A fine needle is conventionally defined as having an outer diameter <
or = 0.9 mm or > or = 19 G. Ultrasound guided fine needle aspiration cytology is
found reliable for diagnosing malignancy. Limitations of this method are
inadequate sampling and limited value in diagnosis of well-differentiated
malignant tumours and benign tumours. Ultrasound guided fine needle cutting
biopsy allows to obtain tissue for histological examination according to the
Menghini technique. Both methods have high sensitivity, specificity and accuracy
in detecting malignancy. In a personal series of 50 fine needle aspiration
cytologies, a sensitivity for malignancy of 87% was obtained, with a specificity
of 100%. The insufficient sampling rate, however, was 10%. Ultrasound guided fine
needle trucut biopsy combines the advantages of a fine needle and a better
sampling quality; a lower insufficient sampling rate can be expected without
increase in complication rate. Despite the availability of numerous manually
operated or (semi-) automated devices, little data have been published up to now
on liver lesions. In our hands, it has proven to be a safe and reliable method,
with low insufficient sampling rate, allowing correct identification of primary
liver malignancies, correct suggestion of the primary source of the majority of
metastases and correct identification of most benign liver lesions. Therefore it
is considered as the method of choice when focal noncystic liver lesions are to
be biopsied.
PMID- 9658600
TI - Treatment of pancreatic pseudocysts by percutaneous drainage. Review and personal
experience.
AB - Pseudocysts are serious complications of acute and chronic pancreatitis.
Asymptomatic pseudocysts require no specific treatment. Symptomatic pseudocysts
can be decompressed by surgical, ultrasonographically and endoscopically guided
methods. In the absence of randomised prospective trials it can not be stated
that one of these technique is superior to others. Ultrasonographic and
endoscopic approaches should be confined to centres with particular expertise in
these techniques.
PMID- 9658601
TI - Viral hepatitis throughout infancy to adulthood.
PMID- 9658602
TI - Epidemiology of hepatitis B and C in Europe.
PMID- 9658603
TI - Noncytolytic mechanisms involved in hepatitis B virus clearance.
PMID- 9658604
TI - Hepatitis B virus mutants in HBsAg positive children.
PMID- 9658605
TI - Genetic heterogeneity and properties of hepatitis C virus.
AB - Hepatitis C virus (HCV) is a member of the Flaviviridae family. Its genome is a
positive single-stranded RNA molecule which comprises three distinct regions: a
5' non coding region, a long open reading frame encoding both the structural and
non structural viral proteins, and a 3' non coding region. HCV circulates in
infected individuals as complex mixtures of genetically distinct but closely
related variants referred to as "quasispecies". The quasispecies nature of HCV
genomes appears to play a major role in viral persistence, cell tropism of viral
variants, pathogenicity and resistance to antiviral therapy.
PMID- 9658606
TI - Mother-to-infant transmission of hepatitis C.
PMID- 9658607
TI - Hepatitis C in children after transfusion: assessment by look-back studies.
AB - Look-back studies to identify paediatric patients with post-transfusion hepatitis
C have been conducted at several tertiary-care hospitals in Canada. A general
look-back study was conducted at the Hospital for Sick Children in Toronto for
the time period December 1985 to May 1990. All patients transfused at the
Hospital for Sick Children during this time period were identified from hospital
Blood Bank records. Letters of notification were sent by registered mail to all
recipients excluding those known to have died. In the letter anti-HCV testing was
recommended. Letters were mailed to 6332 transfusion recipients; 4496 letters
were delivered. Of these 146 anti-HCV-positive transfusion recipients (92 pts <
18 yrs old; 54 pts > 18 yrs old) were identified. Sixty-four of these patients
were definitely transfused only during this time period. Assuming that all
notified patients were tested, the minimum prevalence of new infection in this
time period was 1.4%. When possible, identified patients were tested for presence
of HCV RNA in the serum by RT-PCR. The proportion of patients anti-HCV positive
but HCV RNA negative on one or more occasions was similar in both whole cohort
and subset: approximately one-third. These data suggest that chronic hepatitis C
may be less likely to develop after transfusion in children than in adults.
PMID- 9658608
TI - Natural history of chronic viral hepatitis in childhood.
AB - Chronic Hepatitis B virus (HBV) infection in children is commonly associated with
Hepatitis B e antigen (HBeAg) seropositivity and histologic features of minimal
to moderate hepatitis. Remission of liver disease is the rule following HBeAg to
antiHBe seroconversion and clearance of HBV DNA from serum. In intermediate and
low endemicity areas chronic HBV infection is usually acquired postnatally, and
more than 80% of children are likely to achieve stable remission during the
pediatric age. Severe sequelae, namely cirrhosis and HCC, have been observed only
in less than 4% of children followed over two decades. In all cases cirrhosis was
an early complication. Chronic HCV infection is usually silent in children. The
chronicity rate seems to be high (50-80%) in post-transfusion hepatitis C as well
as in perinatally acquired infection. HCV-associated liver disease is
characterized by fluctuations of ALT which remain below two times the normal in
about half of the cases. Liver histology shows minimal to mild hepatitis in the
large majority of patients and cirrhosis is rare. Few patients achieve
spontaneous remission and progression to a more severe liver disease might occur
in adult life.
PMID- 9658609
TI - Hepatitis B and C in eastern Europe--the current situation.
PMID- 9658610
TI - Risk of hepatitis A superinfection in patients with underlying liver disease.
AB - During recent years the outcome of acute hepatitis A in chronic liver disease has
been discussed controversially. Data from large hepatitis A epidemics and
surveillance data from the United States suggest a significantly higher risk of
fatal outcome in patients with chronic hepatitis B. Patients with chronic active
hepatitis or liver cirrhosis seem to be at highest risk, while HBsAg carriers may
exhibit a benign course of the disease. Patients with chronic hepatitis C also
seem to have a significantly higher risk of fulminant hepatic failure when
superinfected with hepatitis A. The recently reported unsuspected coincidence of
autoimmune markers with a fulminant course of hepatitis A in those patients needs
to be confirmed. Vaccination against hepatitis A in patients with chronic liver
disease has been shown to be safe and effective.
PMID- 9658611
TI - Hepatitis B: long-term outcome and benefits from mass vaccination in children.
AB - Hepatitis B viruses can cause chronic liver diseases in both children and adults.
In hyperendemic areas, although most related complications occur during
adulthood, nearly half of the primary infection in chronic hepatitis B virus
carriers occurs in perinatal period through maternal transmission and the other
half are from horizontal transmission mainly through intrafamilial spread or
injection using unsterilized needles. Children with chronic hepatitis B virus
infection are mostly asymptomatic. They are generally active and growing well
with very rare exceptions. Even with acute exacerbation of liver function and
active inflammation, jaundice or growth failure is uncommon. Mild histologic
abnormalities in the liver begins early in life and may progress to severe liver
impairment in later life. Severe liver damage, with bridging hepatic necrosis or
fibrosis, or cirrhosis of the liver may occur, but is rare during childhood.
Universal immunization program of hepatitis B virus has been proved to be
effective in reducing hepatitis B carrier rate for more than 10 folds, and the
incidence of hepatocellular carcinoma in children has also been reduced
significantly.
PMID- 9658612
TI - Is liver biopsy needed in children with chronic hepatitis?
PMID- 9658613
TI - Hepatitis virus induced autoimmunity.
PMID- 9658614
TI - Interferon: a meta-analysis of published studies in pediatric chronic hepatitis
B.
AB - Perinatally infected Asian children respond poorly to interferon (IFN) therapy.
In contrast, IFN therapy seems to be more effective in Caucasian children who
presumably acquired HBV infection later in life. We reviewed seven controlled
studies of IFN treatment in children with chronic hepatitis B living in western
countries (216 treated, and 200 untreated children). Before treatment all
patients were HBeAg and HBV-DNA +ve, with a biopsy proven chronic hepatitis B.
Ages ranged 1 to 16 years (mean age 7 years). Most patients were Caucasian.
Protocols which have been adopted may schematically be divided into protocols
which have used high doses of IFN (7.5 to 10 MU/sqm/TIW), and protocols which
have used low doses of IFN (3 to 6 MU/sqm/TIW), with a short (3 to 6 months) or a
long duration of treatment (12 months). The percentage of treated patients who,
at the end of treatment, lost HBV-DNA (that in most studies corresponded also to
HBeAg serum conversion) averages 20 to 58% (mean 35.5%) that is much higher than
that observed in controls (range 8-17%; mean 11.4%). A better trend is probably
observed only in patients who received the treatment for a longer period of time.
At the end of treatment, low percentages of patients lost BsAg (range 0-4%; mean
1.1%): again higher doses tend to be more effective than lower doses. In some
studies IFN has been shown to significantly accelerate the termination of viral
replication. Data on longer term outcome of IFN treatment in Caucasian children
are scarce and confirm results obtained at short and at medium-term FU either in
horizontally either in perinatally infected children. Results from few randomized
controlled trials of interferon therapy with prednisone priming in Chinese and
Caucasian children were comparable to results obtained without prednisone. In one
study steroid priming did not potentiate the effect of IFN, however it existed a
tendency of prednisone to improve HBeAg clearance in patients with normal
aspartate aminotransferase, and alanine aminotransferase activity lesser than 100
u/l. In most studies, factors positively influencing response rates of IFN
treatment are represented by severe inflammation in the basal liver biopsy, high
basal levels of serum transaminase, low basal levels of serum HBV-DNA. Vertical
transmission may be considered a factor adversely affecting the response to IFN
treatment both in Chinese and Caucasian population. In general in most controlled
studies, the majority of responders have shown a significant reduction in hepatic
inflammation and transaminase normalization. Children have a low risk of
developing severe IFN-induced side effects. Adverse reactions and worsening of
health-related quality of life were tolerable and did not seem to be a limiting
factor for IFN therapy in young candidates.
PMID- 9658615
TI - Therapy for chronic hepatitis B: nucleoside analogues in adult and pediatric
patients.
PMID- 9658616
TI - Immunotherapy of chronic hepatitis B by anti HBV vaccine.
AB - Vaccine therapy is now used in various infectious diseases. The hepatitis B virus
(HBV) leads to chronic infection in around 5% of patients with a high risk of
chronic active hepatitis which may result in cirrhosis and hepatocellular
carcinoma. The partial efficacy of antiviral therapies (40% of sustained
inhibition of HBV replication), their cost, their possible side effects and the
immune-mediated pathology of HBV infection explain the need of new immune
therapies in treating HBV infection. Experimental and clinical evidences suggest
the usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened
study, forty-six consecutive chronic HBsAg carriers with chronic hepatitis and
detectable serum HBV DNA were given 3 standard injections of the GenHevac B
vaccine at one month interval. Six months after the first injection, 12 patients
(26.1%) had undetectable HBV DNA while 8 others showed significant decrease (more
than 50%) in HBV DNA titers. Six of these 12 responders received a standard
course of alpha-Interferon (5 MU thrice weekly subcutaneously for 4 months) and
all six had still undetectable HBV replication at the end of follow-up. Among the
34 non responders to vaccine, 20 were given alpha-interferon and 2 the
monophosphate derivate of Vidarabine: 12 of these 22 patients stopped HBV
replication and in all 12, vaccine therapy had induced a significant decrease of
HBV replication before the antiviral treatment with a decrease of mean serum HBV
DNA from 392 pg/ml before to 217 pg/ml after vaccine therapy. In an ongoing
controlled study, using the same vaccine schedule, serum HBV DNA disappeared more
frequently after 6 months, in patients who were given a preS2/S vaccine (7/35)
than in patients who received a S vaccine (1/21) or no vaccine (1/32). In
responders to vaccine, an induction of specific proliferative responses was
observed and this may contribute to the potential efficacy of anti-HBV vaccine
therapy. No side-effect or vaccine-induced escape-mutants occurred during the
follow-up. In summary, serum HBV DNA disappeared in 28 of the 46 patients (60.9%)
who were given vaccine therapy, with (64.2%) or without (55.6%) Interferon. These
results are not different at 6 months and at the end of follow-up from those of
43 HBsAg chronic carriers who were given only an antiviral treatment. Active
immune therapy against HBV appears efficient and less expensive than antiviral
therapies in stopping HBV replication. Such results need to be confirmed by the
completed results of our controlled, randomized trial which is now conducted in
our unit.
PMID- 9658617
TI - "Receptor-ligand" based new strategy for treatment of patients with chronic
hepatitis B.
PMID- 9658618
TI - Treatment of pediatric hepatitis C: results and perspectives.
PMID- 9658619
TI - Global status of HB immunization, 1998.
PMID- 9658621
TI - Ethical aspects of pediatric therapeutic clinical trials.
PMID- 9658620
TI - Interferon treatment for chronic hepatitis B or C infection: costs and
effectiveness.
AB - INTRODUCTION: With recognition that resources are limited, health care payers and
policy makers have increasingly turned toward economic analyses to determine
whether particular therapies are an efficient use of economic resources. Both
chronic hepatitis B and C infections can progress to cirrhosis or hepatocellular
carcinoma over time. Interferon treatment has been shown to eradicate viremia,
but only does so in a proportion of treated patients. It has potential side
effects, has no proven long-term benefit on complications and is relatively
expensive. OBJECTIVE: To determine the cost-effectiveness of interferon treatment
by estimating the lifelong economic and clinical outcomes associated with
interferon therapy versus standard care for patients with either chronic
hepatitis B or C infection. METHODS: Computer cohort Markov model simulation to
project the lifelong impact of the loss of hepatitis B or C viremia resulting
from interferon on cirrhosis, life expectancy, and costs. The natural history of
hepatitis B and C was based on published studies. Efficacy estimates for the loss
of viremia were based on meta-analysis of published data. Using a societal
perspective, economic estimates were based on cost of care data for patients with
hepatitis and from estimates regarding the frequency of health resource
utilization provided by expert panels. RESULTS: For 20 year old patients with
either hepatitis B e antigen positive chronic hepatitis or histologically mild
chronic hepatitis C infection, interferon should be cost saving, extending life
and reducing lifetime expenditures and morbidity. Life expectancy should increase
by 4.8 to 3.1 years for patients with chronic hepatitis B or C, respectively.
Lifetime costs should be reduced on average by $6,300 to $6,900 for each patient
treated with interferon. CONCLUSION: Chronic infection with hepatitis B or C can
result in liver failure and death. Although only effective in a proportion of
treated patients, interferon for chronic hepatitis appears to be an efficient use
of societal resources so that economic reasons should not limit its use.
PMID- 9658622
TI - Treatment with lamivudine for non-immunocompromized patients with chronic
hepatitis B.
PMID- 9658623
TI - Treatment with terlipressin as a bridge to liver transplantation in a patient
with hepatorenal syndrome.
AB - Hepatorenal syndrome is a rapidly lethal complication of cirrhosis. The present
case provides further evidence of the efficacy of terlipressin in this context
even with concomitant treatment with propranolol. A 56 year old male with HBV
related cirrhosis developed renal failure characteristic of hepatorenal syndrome.
He was also taking propranolol for primary prophylaxis of variceal bleeding.
Terlipressin 6 mg/day was administered during haemodialysis and after 1 week
plasma creatinine dropped from 6.2 to 2.8 mg%. Daily urinary volume, plasma
sodium and natriuresis dramatically increased during the treatment.
Discontinuation of the treatment led to a rapid relapse of renal failure (plasma
creatinine from 1.8 to 2.2 mg%) and the drug was readministered until a
successful liver transplantation could be performed 1 month after the beginning
of the treatment. The patient has now a near normal renal function 3 months after
transplantation.
PMID- 9658624
TI - [Evaluation of the cochlear aqueduct patency: comparison of 2 noninvasive
techniques].
AB - Variations in cephalo-rachidian fluid pressure can be transmitted to the middle
ear through the cochlear aqueduct (CA). This gives us a non-invasive manner to
evaluate any changes in fluid pressure by measuring middle ear impedance
(impedancemetry). The present study compared two indirect methods for measuring
intracranial pressure: a) impedancemetry during evoked jugulo-tympanic reflex
(JTR) and b) study of the tympanic membrane (TM) fine motility using a MMS-10
analyzer. The latter is a new procedure involving the indirect evaluation of the
fluid pressure. In fact, when the CA is open the labyrinthine fluid pressure is
transmitted to the oval window, the stapes platina and, finally, to the tympanic
membrane where it can be measured with an MMS-10 unit. This equipment can measure
nanoliter shifts in the TM. In particular, comparison between the clinostatic and
orthostatic tympanic motility measurements enable one to establish whether the CA
is patent or not. In the present study 15 subjects were examined using both a)
impedancemetry during jugular compression and b) analysis of the TM shift using
an MMS-10 unit. In 14 of the 15 cases there was good correlation between the data
obtained using both methods: in all but one case it proved possible to record a
JTR-induced variation in impedance whenever the MMS-10 indicated that the CA was
open. The results suggest that, in clinical practice, the two methods can be used
in parallel for non-invasive monitoring of variations in intracranial pressure in
patients with neurological involvement. On the other hand, in the E.N.T. field
these techniques could be used to study inner ear pathologies causing dynamic
alterations of the endolabyrinth fluids (endolymphatic hydrops, labyrinthine
fistula).
PMID- 9658625
TI - [Changes in posture in whiplash evaluated by static posturography].
AB - Analyzing vestibular-spinal reflex by recording changes in the pressure center
over time, static posturography provides precise, repeatable information
regarding a person's posture and subsequent postural strategy. Moreover, using
the detected postural pattern, this can presage likely genesis of problems in
equilibrium. The purpose of the present work was to evaluate posturographic
findings in subjects with chronic or persistent whiplash (WL)-induced
disequilibrium in order to determine any clear postural pattern able to indicate
the likely genesis of the disorder. Fifty young subjects were selected for the
study: 28 (6 females) affected with equilibrium problems resulting from WL-type
cervical strain and 22 (5 females) normal, age compatible controls (C) (mean age
of the groups: WL = 37 +/- 14.3; C = 32.4 +/- 6.7; p = n.s.). The results
obtained were statistically processed with a personal computer and specific
software (Windows-SPSS). In the analysis of the means (T-test and ANOVA analysis
of variance) p < 0.05 was considered significant. In the WL group there was an
increase in the antero-posterior axis oscillation frequency as compared to the
control group. This is indicated by the FFTY parameter in tests performed both
with eyes open and closed. Likewise, in both tests, there was a decrease in the
LFS value, a parameter correlating length with surface. The surface was increased
in the WL group as compared to group C although this increase was significant
only when the test was performed with eyes closed. In addition, the average
velocity and standard deviation of velocity increased in the WL group but this
was only statistically significant when the eyes were open. The results obtained
in the present study show that whiplash victims show an increase in antero
posterior oscillation frequency at the pressure center, as found in the open and
closed-eye tests. This suggests that in WL subjects there is an evident
disturbance of the fine postural system, leading to an increase in the surface
parameters, tracing length and a decrease in LFS function. The onset of this
partial postural decompensation can be seen in: a) decrease in fine static
postural control which is reflected in an increase in body surface oscillation;
b) an increase in energy consumption to maintain orthostatism as revealed in the
decreased LFS. In conclusion, it appears reasonable to assume that cervical
proprioceptive alterations play a preeminent role in the genesis of whiplash
induced chronic postural instability. This would result in an attempt to vary the
physiology from an ankle to a hip strategy; incomplete manifestation of this new
posture would cause the feeling of instability mentioned by the patients and
documented by posturography.
PMID- 9658626
TI - [The contralateral ear in acquired cholesteatoma in children and adults].
AB - Contralateral ear pathologies are frequently found in patients suffering from
acquired cholesteatoma. A retrospective study was performed on 85 pediatric
patients and 105 adults surgically treated for acquired middle ear cholesteatoma.
All the patients were checked and the otomicroscopic picture photographed and
compared in an attempt to gain insight into the pathogenesis and clinical
indications by comparing two samplings from different age groups. In both groups
the frequency of pathological contralateral ear manifestations was higher than
found in the normal population. Similar results were obtained in the two groups
and indicate that the same mechanisms come into play in both ears, starting at
infancy. The finding of a particularly common association between cholesteatoma
and contralateral retraction pockets with sinus cholesteatoma or pars tensa in
the pediatric group appears to confirm that tubal dysfunction plays a pathogenic
role in the genesis of cholesteatoma. From the practical point of view,
systematic preventative measurement of the contralateral ear can lead to a
reduction in major surgery and can affect the choice between open or closed
tympanoplasty. Moreover, it may also condition the precision and length of the
follow-up.
PMID- 9658627
TI - [Surgical treatment of otosclerosis in the aged. Results of retrospective
analysis].
AB - Otosclerosis is, per se, a disease which rarely occurs after the age of 50. This
is why stapes surgery is seldom performed in advanced age and there are few
reports on the topic in the literature. The authors have performed a
retrospective analysis of patients over the age of 65 who had undergone surgery
for otosclerosis in the last 27 years. Out of a total of 3585 surgical
procedures, 106 patients were analyzed. Most of the cases were in the advanced
stages. Assessment of the outcome included pre- and post-operative audiometry,
one year after surgery. Inner ear performance was established by evaluating air
and bone conduction at 0.5, 1, 2, 3 and 4 kHz. The results showed that performing
otosclerosis surgery is worthwhile even in the elderly with mixed auditory
impairment, as long as the air-bone gap is limited to 20-30 dB and the surgical
procedure is through. In this light, stapedotomy appears to be the most adequate
technique. When evaluating the results the possibility of adopting a less
powerful hearing aid should also be considered a success.
PMID- 9658628
TI - [CO2 laser treatment in laryngeal papillomatosis].
AB - Laryngeal papillomatosis is a rare, unpredictable pathology which often recurs.
Although several forms of surgery have been suggested for this pathology, CO2
laser surgery is the treatment of choice. This paper presents 30 cases of
laryngeal papillomatosis, 12 of which arose in infancy, all treated by dissection
and/or CO2 laser vaporization. The treatments were performed in one or more
stages depending on the site and appearance of the lesions. Special care must be
taken to preserve the anatomical integrity when a papillomatosis must be removed
from the glottic area. The average number of surgical procedures per patient
proved greater in multifocal vs. unifocal forms (4.7 vs. 1.6) and in children vs.
adults (4.9 vs. 3.7). In four patients the pathology followed a neoplastic
evolution. Today 57% of the subjects treated (17) are in clinical remission after
an average 17 month follow-up. CO2 laser endoscopic microsurgery is presently the
most suitable method for treating laryngeal papillomatosis although the
biological features of this diseases often make treatment difficult.
PMID- 9658629
TI - [Otoneurological manifestations in Fhar's disease. A case report].
AB - Fhar's disease is a rare idiopathic CNS pathology characterized by widespread
calcifications of the basal ganglia, cerebellar nuclei and endocranial vessels.
The origin of this disease is unknown and a lack of thyroid and parathyroid
pathologies is the main statement. From the clinical point of view,
extrapyramidal manifestations are common while vertigo and equilibrium disorders
are rare. In the present case vertigo and disequilibrium were the main symptoms.
Fhar's disease was diagnosed by CT and MRI showing calcification of the basal
ganglia without any metabolism disorders or thyroid and parathyroid pathology. A
battery of neurotological tests showed alterations of VOR and ocular movement. In
particular the saccades movements showed significant hypometria while the smooth
pursuit showed gain diminution and corrective saccades. These anomalies imply
dysfunction of sub-cortical centers regulating and modulating ocular movement.
VOR alterations included both qualitative anomalies of nystagmus (i.e.
dysrhythmia, square waves) and quantitative alterations (i.e. bilateral deficit
response to caloric and rotatory stimuli). These alterations could be due to the
impairment of cerebellum-vestibular and vestibular-thalamic pathways. Acoustic
evoked potentials (ABR, MLR) ruled out central acoustic pathway dysfunction.
PMID- 9658630
TI - [3 cases of post-stapedectomy labyrinthine fistula].
AB - Three cases are presented of labyrinthine fistula which suddenly arose in
patients who had undergone stapedectomy interposing a vein graft from the back of
the hand. These patients had all enjoyed 12-15 years apparently problem free
period before the fistula occurred. In all three cases the fistula was
accompanied by objective dizziness and varying degrees of sensorineural or mixed
hearing loss. The patients underwent revision surgery which identified the
fistula and the endolymph oozing out of the graft from the previously installed
prosthesis. The authors present the cases, describe how the symptoms arose and
the results obtained with revision surgery. Finally, they discuss the need to
first perform stapedotomy with a platinar hole; they indicate that the number of
cases of total or partial stapedectomy should be limited only to those cases
characterized by anatomical variations and/or whenever complications arise during
surgery.
PMID- 9658631
TI - [Malignant pilomatrixoma of the face].
AB - The authors report a case of malignant pilomatricoma of the right preauricular
region in a 66 year old woman. This is a rare neoplasm and only 36 cases have
been reported in the literature: 10 in the cervical-facial region and 15 of the
scalp. There are problems in differential diagnosis with benign pilomatricoma,
basal cell carcinoma, squamous cell carcinoma, parotid masses and the initial
stages of cutaneous and subcutaneous cysts. Diagnosis of malignant pilomatricoma
is essentially histological. It has a low degree of malignancy but tends to recur
after surgery and to metastasize even leading to death. Treatment of choice is a
broad surgical excision followed by periodic check-ups. Such exeresis was
performed in the case presented and the patient is alive and in good health 67
months after surgery.
PMID- 9658632
TI - [Ancient theories on the genesis of allergic rhinopathy. From the beginnings to
the 18th century].
PMID- 9658633
TI - [Lateral approaches to the clivus].
AB - Thanks to ongoing development in microsurgical techniques to treat the skull base
some clivus lesions, considered inoperable until a few years ago, can now be
removed with relatively low mortality and morbidity. The approaches available for
the treatment of lesions in this anatomical area can be broken down into anterior
and lateral. The latter offer the surgeon several important advantages such as
better control over the main vascular structures and the possibility of opening
the intradural space without coming into communication with the pharynx. By
virtue of their extreme versatility, the lateral approaches may be used in
combination in a single operation or can be performed as staged procedures. Each
of the lateral routes, however, has its own advantages and drawbacks. These are
presented during a brief description of each technique. The main factor in
selection of approach is the anatomical limits of the approach itself. Generally
speaking, the largest surgical field is offered by the most destructive
approaches. Although they do cause such deficits as unilateral hearing loss,
these approaches permit greatly improved control over the vital structures.
Nevertheless, when such deficits exist prior to surgery, the morbidity of such
approaches is negligible. The histological nature of the disease, the variable
relationships with the dura, the main neurovascular structures and other factors
should all be considered when deciding how to manage each case. The surgeon must,
however, have the range of skills required to perform the diversity of approaches
to the lateral skull base so as to provide the patient with the best possible
care.
PMID- 9658634
TI - [Titanium condylar abutment: the contribution of 3D computed tomography].
AB - Various techniques have been described in the treatment of recurrent TMJ
dislocations amongst which, joint arresters form a prominent part. We describe a
new type of bio-integrable joint stop, custom made with 3D-CT help, which
alleviates the two main drawbacks of the technique: lack of retention through
insufficient extension, and secondary mobilization of the stop. Two cases are
reported, amounting to four stops with satisfactory two years follow-up.
PMID- 9658635
TI - Blunt internal carotid artery trauma: report of two cases and review of the
literature.
AB - Blunt injury of the internal carotid artery (ICA) is a rare entity that should be
considered by Maxillofacial surgeons in patients with facial fractures. Its
recognition is often delayed because of the common association with other severe
multi-system injuries. Early diagnosis is the key to successful management; the
arteriography plays a confirmatory role on the diagnosis and determines whether
surgical management of the injury is feasible. Therapeutic alternatives vary from
one center to another; they include observation, conservative treatment,
anticoagulation, ligation of the carotid artery with or without extracranial
intracranial bypass, and arterial reconstruction.
PMID- 9658636
TI - Prognosis value of the expression of Ki-67 for squamous cell carcinoma of the
oral cavity.
AB - Ki-67 is a nuclear antigen expressed in G1, S, G2 and M phase of cell cycle and
absent in quiescent cells (G0). In some neoplasms, Ki-67 expression has a
prognostic value. The purpose of this study was to determine the role of Ki-67
expression like prognostic factor in oral squamous cell carcinoma (OSCC).
Monoclonal antibody MIB-1 that recognizes Ki-67 antigen was used. 74 OSCCs were
analyzed. 49% of OSCCs did not express Ki-67 antigen. In the Ki-67 positive
tumours, the expression was slight in 36.5%, moderate in 10.8% and intense in
10.8% of the cases. In all the positive OSCCs, the distribution of the marking
was patchy in different zones of the tumour, moreover, in 65% of the lesions, the
positive cells were located mainly in the proximity of intraoral blood vessels. A
significantly more intense expression was noted on tumours that had not been
differentiated (p < 0.05), with a larger nuclear pleomorphism (p < 0.05) and in
lesions that invaded in the form of disassociated neoplastic cells of in small
groups of neoplastic cells (p < 0.001). However, the expression of Ki-67 did not
correlate with the mitosis count and it had no influence on survival.
PMID- 9658637
TI - Remodelling of bilateral fractures of the mandibular condyle.
AB - A case of complete remodelling of bilateral fractures of the mandibular condyle
in an 11-year-old boy is presented. Initial radiographic examination revealed
fractures of the right and left condylar neck with medial and anterior
dislocation of the proximal fragment. The fractures were treated conservatively,
with a short-time intermaxillary fixation and early jaw function, and thirty-five
months later the patient was asymptomatic. Radiographic changes observed
following treatment have revealed a gradual return to normal shape and position
of the condyles.
PMID- 9658638
TI - [Diagnostic and therapeutic methods in sleep apnea syndromes. The role of
otorhinolaryngology].
PMID- 9658639
TI - [Current treatment methods for osteosarcoma of the jaw bones].
AB - It is also the most common primary malignant lesion of bone, excluding multiple
myeloma. However it is rare: it occurs in 1 per 100,000 persons per year, and
about 6% tot 7% of all osteosarcomas occur in the maxillofacial region. In this
report, we discuss two cases of osteosarcoma in the maxillofacial region: one in
the mandible and one in the maxilla. It is also a review of the literature. We
discuss in detail the natural history of osteosarcoma in the jaw bones, the
predisposing factors, the localisation, the presenting symptoms, the radiology
and the methods of treatment.
PMID- 9658640
TI - [New perspectives in the treatment of erectile dysfunction].
PMID- 9658641
TI - [Current status of p53 tumor suppressor gene as a possible molecular marker of
cancer of the prostate].
AB - Diagnosis of prostate cancer has increased over the last few years both in
localized and in more advanced stages. At present, several groups are working in
the search and evaluation of alternative tumoral markers as the current ones do
not cover all the Urologist's needs. In this context, a number of studies on the
mutation of the tumour suppressor gen p53 in both localized and metastatic
prostate cancer are being carried out. When a noxa acts on the DNA, protein p53
inhibits the cell cycle allowing the repair systems to operate and, if the damage
is significant enough, cell apoptosis. The loss of this control mechanism
secondary to the synthesis of anomalous proteins can result in the proliferation
of neoplastic cells. A revision of the most representative papers in the
literature is presented here, addressing the surrounding controversy and the
resulting future possibilities.
PMID- 9658642
TI - [Treatment of erectile dysfunction using intracavernous pharmacotherapy].
AB - Intracavernous injection of vasodilators has been the greatest diagnostic and
therapeutical breakthrough in erectile dysfunction (E.D.). After 15 years
experience, these vasodilators have demonstrated efficacy rates over 85%. This
suggests that most cases of E.D. are the result of and inability of the smooth
muscle to relax. This paper presents an overview of the diagnostic and
therapeutic use of intracavernous vasodilating drugs. It includes an extensive
review of the literature and our personal series with regard to efficacy,
indications, contraindications and side-effects of these compounds. Alprostadil
i.c. injection (PGE1) is an effective (> 70%) and safe treatment, and its use has
been accompanied by an increased quality of life of patients, with very few side
effects. Currently, PGE1 is a first choice drug in the treatment of impotence.
When no response is seen, or pain develops after PGE1 administration, a number of
vasoactive compounds associations can be used instead (phentolamine + PGE1,
papaverine + phentolamine, and papaverine + phentolamine + PGE1). The
phentolamine + VIP association has shown encouraging results. Prior to prescribe
IC treatment with vasoactive drugs it is necessary to conduct a basic diagnostic
study, and advise the patient. If treatment is finally accepted, the performance
of adequate training and detailed medical follow-up is crucial.
PMID- 9658643
TI - [Reconstructive surgery with polypropylene mesh associated with kidney
transplant].
AB - OBJECTIVE: There is very little literature on hernial complications of the
abdominal wall in association to renal transplantation. The present report aims
to evaluate their incidence and type, as well as the intervention carried out and
its results. MATERIAL AND METHOD: A retrospective analysis of a series of 650
renal transplantations has been carried out between 1978-1996 in our centre. A
braided polypropylene mesh (Prolene) was used to repair abdominal wall defects
and/or diagnosed hernias in 8 (1.2%) cases: 5 eventrations, 1 inguinal hernia and
one combination of both: the last case required extensive debridement of the
abdominal wall due to necrotizing fascitis. Mean time to eventration was 47.3
months (range 1-106). RESULTS: In all cases, the mesh was placed in the pre
peritoneal space. Two patients developed complications (one haematoma and one
wound infection), though graft removal was not necessary in any case. Follow-up
was 33.1 months (range 6-78) with no findings of hernial relapse. One patient
started successful chronic ambulatory peritoneal dialysis (CAPD) 30 days after
the intervention. CONCLUSIONS: The polypropylene mesh is a sound alternative in
the treatment of hernial complications associated to renal transplantation, with
acceptable morbidity, and efficacy rates that in our series reached 100%.
PMID- 9658644
TI - [Analysis of our series of kidney transplants: urologic complications and
survival].
AB - PURPOSE: To review our series of 416 renal transplants, with special reference to
the surgical complications and their management. METHODS: From June, 1986 to
October 1997, we are performed 416 heterotopic renal transplants, harvested from
cadavers. Reconstruction of the urinary tract reconstruction was by
ureteroneocystostomy in practically all the cases. RESULTS: There were some
urological complications in 80 patients (19.2%). The most common urological
complication was obstruction of the urinary tract arising from stenosis (3.3%),
lymphocele (4.3%) and clotting (1.2%). 78.1% of these urological complications
were resolved by endourological techniques. Urinary fistula was observed in 12
cases (2.8%). Vascular complications in 22 (6.9%), lithiasis in 5 (1.2%), and
eventrations in 11 (2.6%). The treatment of these complications is described. The
actuarial survival rates were 87.8% and 77.3% at one and five years respectively
for the graft, and 92.4% and 83.5% for the patients. CONCLUSIONS: Our surgical
complication rate in patients undergoing renal transplantation was 19.2%. The
most common complication was urinary tract obstruction from stenosis (3.3%),
lymphocele (4.3%) and clotting (1.6%); 78.1% of these obstructive complications
were resolved by endourologic techniques. Percutaneous drainage and
esclerotherapy of the lymphoceles resolved 66.6% of them. Renal biopsy performed
with a 14G needle caused 5 severe hemorrhagic complications. There were no
complications when an 18G needle was utilized.
PMID- 9658645
TI - [Ambulatory treatment of ureteral lithiasis using shock wave extracorporeal
lithotripsy].
AB - Presentation of the results obtained with extracorporeal shock wave lithotripsy
(ESWL) applied to 3173 ureteral lithiasis with a Dornier HM-4 equipment. Location
of lithiasis was pyeloureteral junction (329), lumbar ureter (1068), sacral
ureter (238), iliopelvic ureter (1474) and "lithiasic path" (64). All lithiasis
were treated in situ. Treatments were carried out ambulatory with no anaesthesia.
Treatment/lithiasis rate was 1.3. Percentage of stone-free patients with ESWL
alone was 79.2% after the first session, and reached 86.14% with retreatment.
Percentage of success for lithiasis in pyeloureteral junction was 81.8%, 79.7%
for lumbar ureter lithiasis, 80.09% sacral lithiasis, 90.10% iliopelvic ureter
lithiasis and 79.9% for those in the "lithiasic path". 12.6% lithiasis required
post-ESWL auxiliary manoeuvres. Post-ESWL minor complications (pain, vegetations)
occurred in 5.6% cases and major complications (obstruction, fever, sepsis) in
2.9%. The factors influencing lithiasis fragmentation were the number of shock
waves and the lithiasis duration. Size of lithiasis and presence or absence of
ureteral catheter had no influence. These results suggest that ESWL is an
effective method for managing ureteral lithiasis.
PMID- 9658646
TI - [AIDS and HIV infections in urologic practice].
AB - The infection caused by the Human Immunodeficiency Virus (HIV), a retrovirus,
leads to a progressive decline and to the suppression of cell-mediated immunity
favouring the development of opportunistic diseases and potentially fatal
neoplasias which are practically innocuous in individuals with an intact
immunologic system. The number of AIDS cases recorded in Spain until March 1997
was 45,132, with a revised mortality rate of 58%. Cases in Murcia total 713 up to
October 1997, of which 217 patients are being monitored in the AIDS Unit in our
centre, 414 individuals have died in the region. It is well know that about one
third of patients with diagnosed AIDS or who are HIV carriers will develop some
type of genitourinary lesion, either as a result of a renal disorder, concurrent
or not with HIV, or any other condition directly related to the infection. This
is a report on our Service's experience in the treatment of HIV patients with
genitourinary symptoms that, in a total of 15 cases, required our intervention.
Emphasis is placed on the incidence of nephrolithiasis secondary to therapy with
protease inhibitors over the last few months following introduction of this new
therapeutic tool, prostatitis due to salmonella, and inlaid cystitis among
others.
PMID- 9658647
TI - [Stenosis of the membranous bulbar urethra: our experience in termino-terminal
urethroplasty].
AB - Between May 1989 and August 1996, the Urology Service, Polyclinic of Vigo,
performed 24 termino-terminal urethroplasties in patients with bulbar or
membranous urethral stenosis, measuring 1 to 2.5 cm long. The most frequent
etiologies were iatrogenic (9/24) and traumatic rupture (7/24). After a mean
follow-up of 5.4 years (1 year minimum) the success rate was 80% (19/24) and 20%
(5/24) for restenosis, which were resolved through a single procedure of
endoscopic internal urethrotomy in 3 of the 5 cases.
PMID- 9658648
TI - [Bilateral adrenal pheochromocytoma].
AB - Presentation of one case of bilateral suprarenal pheochromocytoma as early
clinical evidence of a type 2 MEN, which at the time of diagnosis was a bilateral
lesion. The presentation form was a picture of shock with HBP. Labetalol i.v. was
used for initial control and phenoxybenzamine in the pre-operative. Diagnosis was
achieved by biochemical (metanephrine) and radiological (CAT) testing. The
patient was managed with bilateral suprarenalectomy through a single, anterior
incision and abdominal cavity examination. The investigation of the remaining
conditions that conform this syndrome was continued and a familial routine study
implemented.
PMID- 9658649
TI - [High-flow priapism after perineal trauma].
AB - We report on the case of a 19-year-old man with post-traumatic high-flow priapism
that appeared after riding on a mountain bike. Laboratory test (cavernous blood
gas measurement) and image studies (color flow Doppler ultrasound and
arteriography of the internal pudendal artery) that confirmed the diagnosis are
depicted. He was successfully treated with selective percutaneous arterial
embolization with autologous blood clot, recovering a normal erectile function.
PMID- 9658650
TI - [Wunderlich syndrome caused by the rupture of a simple cyst in a patient treated
with acetyl salicylic acid].
AB - Report case of a Wunderlich syndrome due to spontaneous rupture of a simple renal
cyst. The patient is a 77-year old, hypertensive female who was on routine
treatment with Aspirin. The rarity of retroperitoneal haemorrhage with this
origin is documented; also the influence of aspirin as predisposing factor for
this condition is ruled out. Brief evaluation of the various diagnostic means
available. An accurate evaluation that may allow to adopt a conservative aptitude
is recommended.
PMID- 9658651
TI - [Rectorrhage as an unusual extrarenal complication after ESWL].
AB - We report a case of rectorrhage due to an hematoma of sigmoid colon post ESWL in
a patient with chronic hepatopathy and right ureteral calculus. We comment the
clinic and endoscopical study, as well as the review of literature.
PMID- 9658652
TI - [Inverted papilloma of the ureter. Apropos of a case].
AB - Presentation of one case of inverted papilloma of the renal pelvis, an uncommon
entity with very few cases described in the international literature. The
pathoanatomic presentation is that of a benign tumour, which would provide an
option for conservative therapy through segmentary resection and termino-terminal
anastomosis. Due to its low frequency, pre-operative diagnosis of this tumour is
difficult, although the number of diagnosis could be increased with the use of
endourologic techniques. In spite of the benign nature, it can be multifocal and
relapsing. A close follow-up monitoring is recommended.
PMID- 9658654
TI - [Prostatic abscess caused by anaerobic germs].
PMID- 9658653
TI - [Bilateral candida bezoar of the upper urinary tract].
AB - Fungal urinary tract infections are due to candida albicans as first responsible
germ. This sporulated oval fungus divides itself by gemmation and produces
pseudohyphas when it is spread in culture mediums, organic tissues or their
exudates. The most frequent predisposing factor is diabetes mellitus. Others
predisposing factors are: long antibiotic administration, corticoids,
immunosuppressors, neoplasias, neurogenic bladder, and catheter or foreign bodies
into the urinary tract. Bezoar formation is a rare complication that sometimes
produces obstructive uropathy. Although Candida albicans is the most frequent
observed germ in bezoars, Candida tropicalis, Penicillium, Aspergillus, Mucor y
Turolopsis have been found as well. We present the case of a diabetic patient
with a bilateral bezoar formation into the upper urinary tract due to Candida
albicans. Clinical features, diagnosis and treatment are described emphasizing in
the are bilateral onset.
PMID- 9658655
TI - [Testicular abscess: a manifestation of tuberculosis].
AB - OBJECTIVE: Presenting 3 cases of tuberculous epididymo-orchitis not very frequent
presentation without renal or pulmonary involvement. PATIENTS AND RESULTS: 3 old
males of 65 years went for increase of scrotal volume, pain, fluctuation, and
pyocele. 2/3 cases had antecedents urologic, any had pulmonary or renal
antecedents. In the 3 cases there was necessity of practicing trans-scrotal
orchiectomy, since they went later. The urine cultures, excretory urogram and
chest films were normals. CONCLUSIONS: In the patients that they got scrotal
abscess or fistulous tract, should discard tuberculosis.
PMID- 9658656
TI - Diagnosis and treatment of renal and ureteral calculi.
AB - Nephrolithiasis affects about 0.2% of the US population annually with about 5% to
15% of the population suffering at some point in their lives. While 75% of all
calculi are calcium based, the remainder are composed of uric acid, cystine,
struvite, or are composed of more than one substance. A 1997 policy update by the
American Urological Association recommends that stones lodged in the ureter that
are not causing excruciating pain for the patient are best initially managed by
observation.
PMID- 9658657
TI - The use of exhaled carbon monoxide for the diagnosis of carbon monoxide
poisoning. A case report.
AB - INTRODUCTION: Carbon monoxide (CO) poisoning is difficult to confirm in small
rural hospitals that lack easy access to a cooximeter. A small hand held device
can be used to assess exhaled CO (ECO) in parts per million. This device is often
used in smoking cessation clinics to confirm that a person has abstained from
smoking. CASE SUMMARY: A 47-year-old white male became dizzy and had a near
syncopal episode while working on his boat in the local marina. He was brought to
the ER and was found to have an exhaled CO level of 180 ppm. The presence
carboxyhemoglobin (HbCO) was confirmed later by an independent reference
laboratory and the result was 26% HbCO. DISCUSSION: The patient's exhaled CO
level dropped slower than expected while breathing oxygen delivered by a non
rebreather mask. This could be due to inadequate compliance to oxygen therapy and
a fiO2 somewhat less than 1.0. Another limitation of the technique is the
calibration gas (50-ppm CO). This concentration may be too low to assess ER
patients. Therefore a confirmatory ABG with cooximetry should be obtained if
available. Clinicians are cautioned that there is no safe level of HbCO (6).
There is a simple formula to convert ECO to HbCO. The use of exhaled CO
monitoring may be a promising alternative that is relatively less expensive than
cooximetry in the ER setting, but more research is clearly indicated.
PMID- 9658658
TI - Medical malpractice tort law--a benighted system.
PMID- 9658659
TI - [Meningoencephalocele: microsurgical endonasal approach. Report of two cases].
AB - Neurosurgery is the commonest way of treating meningoencephaloceles, but there
are cases with certain particularities allowing microsurgical approach through
the nose, for instance nasoethmoidal sitting, small size,... We report our
experience of 2 cases of meningoencephalocele removed through this approach, one
of them reoperated because tumor recurrence.
PMID- 9658660
TI - [Cavernous hemangioma of the larynx in an adult. Endolaryngeal excision].
AB - We present a case of cavernous laryngeal hemangioma in an elderly lady. The
limited surface of the lesion and its location and implantation basis as well
allowed an endolaryngeal surgery.
PMID- 9658661
TI - [Craniofacial development in secretory otitis].
AB - The AA. consider in a population of 76 children, the connexion between bony
palate, choanae and the M. tensor veli palatini and the occurrence of secretory
otitis. They measured for this purpose several craniofacial structures "in vivo".
Children suffering secretory otitis presented, contrary to children without aural
pathology, a greater incidence of gothic palate (p < 0.001) and a significant
decrease of both palatine (p < 0.05) and choanae (p < 0.001). All children showed
going through puberty an palatinal and choanal growth as well a closure of the M.
tensor veli palatini angle.
PMID- 9658662
TI - [Influence of the necessity of transfusion in anemia on the prognosis of ENT
cancer in the protocol with concurrent hyperfractionation of carboplatin and
irradiation].
AB - Because of the determinant role of hemoglobin level in blood to the response of
treatment (viewpoint admitted whether for irradiation or chemotherapic agents)
the AA. have lead an analysis of a group of 36 patients suffering an advanced
head and neck cancer (18 months mid-follow up and 30 months maximum) which
underwent a program of concomitant radio-chemotherapy hyperfraccionated with
carboplatin (the cytostatic) as part of each therapeutic fraction. The results in
patients being transfused with an erytrocyte concentrate were compared with those
from patients not having had any transfusion. The purpose of this study was the
assessment of which are the influence on the prognostic of ENT-cancer resulting
of the compulsory necessity of transfunding erytrocyte concentrates aroused by
serious anemia presenting during the development of the schedule treatment. In
brief, in that kind of patients needing transfusions of red blood cells
concentrates because of serious anemia during the treatment (17% of the totality
treated) were recorded 50% local failures, 33% metastases and only 17% of the
totality were free of neoplasma at the end of the follow-up fixed. Instead
between patients not having had transfusions (for treating anemia) the
differences registered were 20% failures of loco-regional control and 13%
metastases, whereas 67% were free of tumor at the end of the study. The
conclusion drawn out is: the important influence on the prognostic of these
tumors, when in the course of the scheduled treatment, appear severe anemia
making the transfusions compulsory.
PMID- 9658663
TI - [Submaxillary sialolithiasis due to Actinomyces israelii. A case report].
AB - Actynomicosis of the submaxillary gland is a very uncommon infectious disease. In
this article one case of submaxillary sialolithiasis by actynomices israelii in a
young girl is presented. We discuss several aspects of its diagnosis and
therapeutic possibilities and review the literature on the subject. We emphasize
the interest and value of performing a microbacteriological, mineralogical and
pathological study of the calculi.
PMID- 9658664
TI - [Lingual thyroid. A case report].
AB - Account on a tongue thyroid case and bibliographic review of the subject. It is
an anomaly due to the thyroid gland not come down. Symptomatic cases are scarce
(around 400 reported in the literature). Diagnosis is basically scintigraphic.
When there are symptoms management should begin with thyrotoxine. More severe
instances require surgical exeresis.
PMID- 9658665
TI - [Reconstruction of a palatal defect with pedicled myomucosal flap of buccinator
muscle].
AB - The myomucosal flap from buccinator muscle is a versatile flap useful on
reconstruction of defects located in the palatine region. We report the case of a
vascular tumor located in the left palate which was removed and rebuilt with a
myomucosal flap taken from buccinator muscle. We proceed previously to the
embolization of its nutritional artery (a. palatina major).
PMID- 9658667
TI - [Petrous bone approach for the surgery of petroclival meningiomas].
AB - Four patients, 3 woman and 1 man, with giant petroclival meningiomata are
presented. In all cases the tumor size exceed 44 mm in its greater diametre. Main
clinical symptoms were endocranial hypertension and cranial nerves deficit. A
modified transcochlear approach in two stages was used. A total petrosectomy was
performed, using the petrosygmoidal via for opening the dura. Transversus and
sygmoid sinus were spared. Total removal was achieved in 2 cases, subtotal and
partly in each of the other 2. No operative mortality occurred (hospital exitus)
and neurologic morbility related to V-VI-VII and VIII cranial nerves and 1
hemyparesia was recorded. The AA. explain and comment the fundamentals of the
followed procedure and compare, as well, the own outcomes with those reported by
more classic alternatives. Finally, the conclusion is drawn out that retroclival
meningiomata are conditions treatable, although always are difficulty approached
and demand meticulous microsurgical techniques.
PMID- 9658666
TI - [Deep infections of the neck].
AB - Infections of aponeurotic sheets of the neck are more frequent in men than in
women. Its etiology although varied is basically related to infectious pharyngo
tonsillar and dental pathology. In a great deal of cases there are factors which
predispose clinical manifestations or becoming complications. Early diagnosis and
precocious specific treatment re-establish the normality in the majority of cases
but a percentage of them resort to surgery for the condition's control.
PMID- 9658668
TI - [Efficacy and safety of dotarizine vs. cinnarizine in the symptomatic treatment
of acute balance disorders (common vertigo)].
AB - One hundred and ten adult patients suffering from peripheral vertigo were treated
in a multifactorial double-blind randomized clinical trial with dotarizine (50 mg
b.i.d.) or cinnarizine (75 mg b.i.d.). There was a 60 days clinical follow-up.
Results showed that dotarizine was significantly active against the vertigo
attacks and its associated symptoms (mainly neurovegetative). The global
superiority of dotarizine was confirmed by statistically significant differences
between treatments in the improvement of the severity of vertigo, hearing loss in
audiometries, global relief of symptoms, disability produced by crises and global
assessment by the investigators themselves. No clinically significant unwanted
effects were seen in either group on blood pressure, heart rate or analytical
parameters. No serious adverse effects to dotarizine were reported. This study
confirms the value of dotarizine in the treatment of peripheral vertigo.
PMID- 9658669
TI - Comparison of different approaches for a survey of the general population.
PMID- 9658670
TI - [Microbiological studies of waters of the Alimini Lakes].
PMID- 9658672
TI - [Dietary exposure to cadmium and mercury].
PMID- 9658671
TI - [AIDS: knowledge, attitudes and sex behavior of young people attending AIED
family planning health services].
PMID- 9658673
TI - [Protection from biological agents in the workplace: considerations on section
VIII of the Legislative Decree 626/94].
PMID- 9658674
TI - An early-type hypersensitivity (ETH) to hepatitis B surface antigen as a quick
and economic screening test for a vaccination program.
PMID- 9658675
TI - [Monitoring of sterilizer equipment in a large Roman hospital].
PMID- 9658676
TI - [Fiuggi mineral water: clinical reality and pharmaco-therapeutic attributes].
PMID- 9658677
TI - [Post-traumatic stress disorder: will the future be different from the past?].
PMID- 9658678
TI - The epidemiology of chronic fatigue syndrome.
PMID- 9658679
TI - [Mania: clinical and epidemiological features in different periods of life].
PMID- 9658680
TI - The epidemiology of eating disorders.
PMID- 9658681
TI - Can deinstitutionalised care be provided for those at risk of violent offending?
AB - OBJECTIVE: The aim of this article is to explain the current status of
deinstitutionalisation and of community care development in the UK. DESIGN:
Literature review of articles and reports on deinstitutionalisation. SETTING:
Articles included in the review related either to the whole of the UK, to England
and Wales, or to a specific area such as London. MAIN OUTCOME MEASURES: The
review was carried out pertaining to the question of the extent to which
community care can or should take over the functions of the asylum, with
particular reference to those at risk of behaving violently. These functions
include those that are manifest, or explicit, and those that are latent, or
unintended but implicit (Bachrach, 1976). RESULTS: The example of patients at
risk of violent behaviour is-one that highlights the continuing relevance of both
these sets of functions, which are argued to be exerting a powerful influence on
the processes of asylum closure and community care development. This influence is
seen in delayed asylum closure, transinstitutionalisation (the shift of some
patients from asylums to other institutions), and the institutionalisation of
aspects of community care. CONCLUSIONS: Both the manifest and the latent
functions of asylums must be acknowledged by those involved in planning community
care; where it is felt desirable that community care does not take over certain
functions, the consequences of this must be anticipated so that they can be
prevented or dealt with in other ways.
PMID- 9658682
TI - [Physician-patient interactions: a comparison of analysis systems].
AB - OBJECTIVE: The medical interview has important diagnostic and therapeutic
functions and requires the integration of doctor-centred and patient-centred
interviewing techniques to collect accurate and complete biopsychosocial data
from the patient. Analysis of the interaction between patient and doctors which
occur during the medical interview allow to evaluate physicians' interview
techniques and to eventually improve them. OBJECTIVE: 1. To review different
Interaction Analysis Systems (IAS) used to describe doctor-patient communication
in terms of clinical relevance, observational strategy, reliability and
behavioural and verbal contents. 2. To critically evaluate these IASs on the
basis of their relevant research outcomes. METHOD: Previous reviews on
interaction and keywords for Medline research (HealthGate) listed above were
utilised to collect the relevant literature. RESULTS: Seventeen classification
systems were identified and ten were discussed in a chronological order. Starting
from a general sociological or psycholinguistic approach, the IASs over the years
have became more specific and detailed, focusing more on the medical interview
and on specific topics, such as cancer or hospital medical consultations.
CONCLUSIONS: When studying interactions in general practice medicine, it is
important to define the significant units of interaction which allow to identify
a "patient-centred approach", since this is relevant not only for obtaining
reliable and complete medical and social data, but also for the recognition of
patients with emotional disorders and their correct diagnosis. Listening to the
patient and facilitating the expression of emotions is an important aspect of
patient education too, as patients learn that talking about psychological
problems to their physician is appropriate and may be therapeutic.
PMID- 9658683
TI - [Alcohol Use Disorders Identification Test (AUDIT). Presentation].
PMID- 9658684
TI - From megakaryocytes to platelets: platelet morphogenesis takes place in the
bloodstream.
AB - We studied megakaryocyte processes formed in rat bone marrow and spleen, using
both the transmission and scanning electron microscopes. Some processes were
bulky, others slender and beaded. The bulky megakaryocyte processes developed a
specialized arrangement of organelles at the site at which they entered the
lumen: filaments present around the outside of the process seemed to support a
central cylinder in which organelles flowed along microtubules. Megakaryocyte
processes were present in platelet-rich plasma from both human and rat blood.
When followed in living preparations, bulky processes developed pointed tips,
elongated, and became slender and beaded. Fusiform proplatelets also were present
in the platelet rich plasma, with pointed tips at both ends of what appeared to
be single "beads"; we assume that the long, beaded megakaryocyte processes would
have fragmented were we to have had proper culture conditions. The straight,
shorter fusiform proplatelets in living preparations underwent characteristic
curving and bending motions, eventually forming disk-shaped cells which sometimes
had appendages. This behaviour suggests that the entire process of platelet
morphogenesis takes place in plasma: megakaryocyte processes first elongate, then
bead and fragment, and then curve and fuse to form disk-shaped platelets. This
interpretation is strengthened by finding in freshly isolated plasma many of the
shapes seen in the transformations studied in living cell preparations. The
megakaryocyte processes and the proplatelets seemed to appear in plasma with a
periodicity related to light and dark cycles--that is, with a circadian rhythm.
In particular, megakaryocyte processes appear in human blood within a few hours
after sunrise; we argue that this might be related to similar peak periods for
heart attacks.
PMID- 9658685
TI - A review of the use of teicoplanin in haematological malignancy.
AB - Factors determining the change in patterns of antibiotic use in patients with
haematological malignancies include the growing numbers of infections caused by
Gram-positive pathogens, the increasing reliance on indwelling catheters, and
strategic movement away from inpatient therapy towards day-case and non-inpatient
therapy. The suitability of teicoplanin in this context is examined. The
indications for teicoplanin use are now established as: early use in clinically
infected patients; as a second-line agent for sensitive pathogens; and in primary
antibiotic failures. Teicoplanin should not be used as empirical therapy in
fevers of unknown origin; neither should teicoplanin be used as prophylaxis (the
situations of infection in chemotherapy patients or for Hickman catheter
insertion in particular are discussed). Comparative studies versus vancomycin
have shown teicoplanin to be equally effective and to be well tolerated.
Teicoplanin's good safety profile and ease of use make it particularly useful for
non-inpatient therapy. Problems are posed for both glycopeptides by specific
resistant pathogens, although these pathogens are currently not common.
Haematologists must be aware of, and guard against, abuse of the glycopeptides in
their own and other fields, including oral gut decontamination, the treatment of
Clostridium difficile and veterinary use.
PMID- 9658686
TI - Non-inpatient parenteral antibiotic therapy in febrile adults.
AB - Non-inpatient care is becoming an increasingly attractive option in many
therapeutic areas, including the treatment of infections in patients with
haematological malignancies. The choice of antibiotics for this care is governed
by infection patterns and experience within particular institutions. There is an
increase in infections caused by Gram-positive pathogens due to the long-term use
of tunnelled catheters and intensive, punishing chemotherapy regimens. Patients
suitable for non-inpatient care include both long- and short-term patients who
fulfil specific clinical and social criteria. Haematological malignancy patients
are often suitable for this type of care. Benefits for patients include improved
quality of life, while benefits for the clinician include effective, safe care as
well as reduced costs and greater bed availability. The glycopeptide teicoplanin
has been assessed for use in non-inpatient care, and is particularly suitable due
to its long half-life, no need for monitoring and its activity against Gram
positive pathogens. A comparative study of a teicoplanin-ciprofloxacin
combination was conducted in inpatients, followed by a cohort study in non
inpatients. This combination was found to be clinically and microbiologically
effective, suitable for non-inpatient administration and generated cost savings
due to early discharge. The organization of a non-inpatient service demands
dedicated team members, with well-defined roles and a designated treatment area.
The day ward is the focus of care, which can then take place in the day ward or
in the patient's home. Good communication between immediate and wider team
members, and patient education are cornerstones of a successful service.
PMID- 9658687
TI - Experience with teicoplanin in non-inpatient therapy in children with central
line infections.
AB - Indwelling intravenous catheters are an invaluable part of the curative therapy
or terminal care of children with haematological malignancies. The increase in
their use has been paralleled by an increase in Gram-positive infections,
however. This article provides an overview of non-inpatient treatment of central
line infections using teicoplanin. The main drivers for considering non-inpatient
therapy were to increase the quality of the patient's life by reducing the amount
of time spent in hospital, and to prolong the life of the catheter. A large
proportion (95%) of the children in the unit described have indwelling catheters
in situ, including Port-a-caths, Hickman catheters and Vascaths. The indications
suitable for non-inpatient antibiotic therapy of line infections were those
patients near the end of their chemotherapy courses, during terminal care, in non
neutropenic patients to complete an antibiotic course, and in patients with
chronically neutropenic aplastic anaemia. Persistent line infections are not
always eradicated but usually controlled. Care can take place in the home, in the
general practitioner (GP) surgery or in the outpatient clinic. Care can be
undertaken by nurses, older patients and parents. Follow-up procedures are in
place to ensure safe, effective therapy.
PMID- 9658688
TI - Central venous catheter infections treated with teicoplanin.
AB - A novel way of using teicoplanin in situ to treat central venous catheters is
described. Profound immunosuppression and the fact that the lines remain
indwelling for long periods are two of the main reasons for these infections. In
children it is also difficult to prevent these lines being played with, which
increases the likelihood of infection. The different types of infection that can
occur in a central venous catheter are described and the clinical definition of a
catheter infection is provided. In an initial study, infective episodes in a
small group of 11 children were treated successfully with in situ amikacin. Most
pathogens were Gram-negative cocci. None of the catheters had to be removed, and
catheter life was prolonged by a mean of 118 d. Due to the high incidence of
Staphylococcus epidermidis in the initial study, in situ teicoplanin was assessed
in a subsequent study. Over the course of 1 yr, 20 line infections occurred in 12
children. Empirical amikacin therapy was instituted and switched to teicoplanin
once the pathogen was confirmed as Gram-positive. An antibiotic-heparin mixture
was introduced into the line and left in place for 24 h, after which time it was
replaced with fresh mixture until cultures were sterile. All pathogens were
sensitive to teicoplanin, all infections were treated successfully and no
catheters had to be removed. Overall, catheter life was prolonged by a mean of
136 d. It was concluded that in situ teicoplanin was effective and well tolerated
for line infections (no side-effects were reported during the study). A minimum
of 6 d therapy was recommended. The patients with less severe infections would
have been suitable for treatment at home by their parents, district nurse or
general practitioner (GP).
PMID- 9658689
TI - Patient education and communication in non-inpatient intravenous therapy--a
review.
AB - This paper reviews patient education and communication elements of non-inpatient
intravenous therapy schemes in the United States and the United Kingdom. Common
characteristics of these services include: definition of the components of the
scheme at all levels; patient selection; patient education; and good
communications. A metaplan carried out among UK healthcare professionals
highlighted education and communication issues as important factors for ensuring
successful therapy. Communication issues are difficult to define or modify.
Specific experience from the United States and the United Kingdom is presented
and the common elements in these programmes are emphasized. Results of the
assessment of patient education are presented. This collective experience may
prove useful for other centres setting up similar therapy schemes.
PMID- 9658690
TI - [Restoration of root canal treated teeth using carbon fiber posts].
AB - The restoration of root canal treated teeth--because of the significant loss of
tooth structure--is often achieved with post and core. However, post may generate
stresses which lead to vertical root fracture and loss of the tooth. Since post
design, material used and the post space preparation has significant influence on
vertical fracture prevalence, broad investigation is in progress to find out the
optimum procedure. During the last decade new prefabricated passive posts were
introduced for postendodontic restorations. In order to collect information
clinical trials have been performed on the reconstruction of root canal treated
teeth using carbon fibe posts (COMPOSIPOST, RTD, France; C-POST, Bisco, USA).
Adhesive technique was applied to cement posts in the root canal and for
composite core reconstruction. The physical properties of carbon fiber posts and
the composite core are very close to those of dentin. Post application is simple,
does not require special skill and for the patients means minimum hazard. The
position of the posts was controlled by radiography. During the 24 months
observation period no failure was registered in patients treated (n = 55). Hence,
we attribute our good results to the homogeneous reconstruction of the teeth.
This procedure seems to be a good alternative to traditional cast metal
dowel/cores or metal prefabricated posts.
PMID- 9658692
TI - [The development of the Simon system and its use in combination with multi-band
technic].
PMID- 9658691
TI - [Efficacy of short-term danazol treatment in hereditary angioneurotic edema
patients undergoing maxillofacial and dental surgical procedures].
AB - The authors evaluated the efficacy of short-term danazol prophylaxis in 12
hereditary angioedema patients undergoing maxillofacial or dental procedures.
Hereditary angioedema is an autosomal dominant disorder resulting from the
deficiency of the C1 esterase inhibitor. Characteristic clinical manifestations
include the formation of subcutaneous and submucosal edema. The latter can lead
to fatal upper airway obstruction. Edematous attacks can be precipitated by
tissue injury from operative procedures, dental surgery in particular. In
patients undergoing surgical and diagnostic procedures performed in the cephalic
and cervical regions, such attacks can be prevented by appropriate drug therapy.
Short-term danazol prophylaxis was effective in all 12 patients with a history of
edematous complications that had occurred after dental procedures; none of them
developed postoperative edema. The serum levels of complement components
determined pre- and postoperatively as well as at 6- and 12-hour intervals also
demonstrated the efficacy of prophylactic therapy.
PMID- 9658693
TI - [Final results of the administration of biosynthetic growth hormone. Preliminary
report].
AB - From March, 1987 to November, 1995, we have included 89 growth hormone-deficient
children for treatment for their low height with the biosynthetic growth hormone;
23 of them have concluded treatment. Without taking into account the etiological
factor of their deficiency, 6 girls and 17 boys during different lapses had
modified their initial height and the scores of the standard deviation as groups,
range from 113.11 +/- 14.83 cm and -5.12 +/- 1.21 to 139.11 +/- 8.96 cm. and
2.68 +/- 1.17 in the girls, and from 128.46 +/- 12.49 cm and -4.13 +/- 1.35 to
158.61 +/- 6.47 cm and -1.76 +/- 0.9 in the boys, respectively. These results
between the initial height and the score of the standard deviation compared with
the final height and the standard deviation score, showed a statistically
significant difference of p < 0.001 both in girls and boys. Two girls and 3 boys
developed hypothyroidism during the treatment, without any other side effect. We
concluded that early and prolonged biosynthetic growth hormone administration in
growth hormone-deficient children might produce a final adult height similar to
the normal population standards.
PMID- 9658694
TI - [Comparative study of tympanic and mercury thermometry in children].
AB - The aim of the study was to evaluate tympanic thermometry when compared with
conventional glass-mercury thermometry, in 186 consecutive pediatric patients. In
patients of less than 6 years of age (n = 120), there were no differences between
tympanic and rectal measurements, in febrile and afebrile ranges, and
significantly different when compared with axillary range. Similar data were
reported in children of more than than 6 years of age (n = 65), in whom oral
temperatures replace the rectal one. Using the tympanic thermometer as the
standard measurement device, the accuracy of rectal, oral and axillary
thermometers in determining a febrile state was examined. When tympanic
temperature was 38 degrees C, a febrile state was considered, in this condition
sensitivity for rectal measurement was of 73%, for oral 64%, and 23 and 29% for
the axillary, according to the age group: specificity was of 100% in all the
them. According to our data, tympanic measurement was consistent with glass
mercurial, rectal and oral, temperature in a pediatric population. Advantages of
tympanic thermometry are its good correlation with central temperature,
substantial time reduction of measurement (1 second), easy and non-invasive
procedure, improved patient comfort, and lack of mercurial thermometry
disadvantages. The conclusion is that tympanic thermometry becomes an acceptable
option for pediatric temperature measurement.
PMID- 9658695
TI - [Chronobiological profile of arterial blood pressure and heart rate in a family
group determined by automatic monitoring].
AB - Over a week, blood pressure (systolic, mean and diastolic) and heart rate were
determined in a family, by means of automatic, uninterrupted monitoring. The
chronobiological profile for each family member was prepared in time series of
various periodicities. An ample circadian component and a lesser circaseptan
component were apparent. Clear phase differences were identified among the four
cardiovascular variables studied. The chronobiological profile of the children
was closer to that of the father than to that of the mother.
PMID- 9658696
TI - [Usefulness of the ASA scale and thoracic radiography as indicators of
perioperative cardiovascular risk].
AB - This paper evaluates the usefulness of ASA physical status classification and the
multifactorial index of cardiac risk in the preoperative assessment, without
considering arterial blood gases. With the results of this study we propose to
add the ASA physical status classification, the radiologic diagnosis of chronic
obstructive pulmonary disease and the multifactorial index of cardiac risk. This
strategy increases the diagnostic certainty of Goldman's index of cardiac risk,
is practical, not expensive and favors a better establishment of the risk of
perioperative cardiovascular morbidity.
PMID- 9658697
TI - [Presidents of the Academy in the 20th century. Their thought].
PMID- 9658698
TI - [The general practitioner in Mexico: present and future].
PMID- 9658699
TI - [Neurosteroids. Neuromodulators of cerebral excitability].
AB - Steroids which are produced by the brain are called neurosteroids, and they are
able to modulate neurotransmissions: GABAergic; glutamatergic; glycinergic, and
cholinergic (nicotine receptor). These effects are of short latency and duration,
and do not implicate the cellular genome. The interaction of these neurosteroids
with membrane receptors contribute to the regulation of neuronal excitability,
and their study has allowed a better understanding of cognitive, hormonal, and
epileptic phenomena as well as the development of new drugs with anxiolytic,
antidepressive, anesthetic and anti-epileptic effects.
PMID- 9658700
TI - [Treatment of diabetic neuropathy].
AB - Diabetic polyneuropathy is a complication, that affects most patients with
longstanding diabetes mellitus, deteriorating their quality of life. In the last
few years, new therapeutic approaches have been developed that can improve
symptoms and neurologic function, and which may prevent and in some cases stop
nerve damage, and even, promote nerve fiber regeneration. These treatments are
supported by several investigations in animals and humans: a) thigh glycemic
control (insulin), b) aldose reductase inhibition (tolrestat), c) prevention of
protein glycation (amino-guanidine), d) improvement of nerve ischemia (vaso
dilators, gamma-linolenic acid), and e) administration of neurotrophic factors
(gangliosides). Most evidence support the usefulness for glycemic control. Early
treatment is suggested, because marked nerve fiber loss is present in advanced
neuropathy.
PMID- 9658701
TI - [Dr. Carlos Adalid and heart catheterization].
PMID- 9658702
TI - [Surgical treatment of invasive thymoma with superior vena cava syndrome. 3 case
reports].
AB - Three patients with invasive thymoma and superior vena cava syndrome with severe
symptoms of cerebral venous hypertension and respiratory obstruction are
presented. Two patients showed a type I obstruction and the other had a type II
obstruction as defined by Stanford and Doty. In all of them, the tumor was
resected and a graft bypass was placed between the left innominate vein and the
right appendage. In two patients the grafts were venous and in the other it was a
PTFE. All grafts were reinforced with wire rings. The patients improved and the
symptoms of the SVCS disappeared, the average time of permeability was 10 months.
PMID- 9658703
TI - [Tridimensional representation of left ventricular perfusion during
pharmacological stress and rest in patients with myocardial ischemia].
PMID- 9658704
TI - [Infectious proteins or prions. A new mechanism of disease].
PMID- 9658705
TI - [Obesity has gone from being a cosmetic problem to being a health problem].
PMID- 9658706
TI - [Gastric cancer and its relations with life style].
PMID- 9658707
TI - [The physician, ethics and the law].
PMID- 9658708
TI - ["Evidence-based medicine"--guidelines as a threat or necessity for physician and
patient?].
AB - Guidelines derived from 'evidence-based medicine' are supposed to provide
assistance and information in order to improve diagnosis and therapy of
individual patients and build up confidence in medical decisions. Guidelines
possess no direct legal power. The doctor's freedom of decision must be
warranted. Inadequate guidelines may have serious consequences: curtailment of
therapeutic freedom, hampering of medical progress, deterioration of the
relationship between doctors and their patients, risk of legal implementation and
emergence of a defensive medicine.
PMID- 9658709
TI - [Operation or irradiation of cervix carcinoma?].
AB - Treatment of early invasive carcinoma of the uterine cervix by radical surgery or
radiation continues to engender controversy after many decades of effective
therapy. A recently published first prospective randomised trial revealed that
stage I and IIa cervical carcinoma can be cured by radical surgery or
radiotherapy with an identical 5-year survival (83% in both groups) and a similar
recurrence rate (25 vs. 26%). In many points, a prospective Italian study
confirms the retrospective results of our previous published studies. Surgery and
radiotherapy alone are equally effective but differ in associated complications.
Severe morbidity occurred in the Italian study after surgery and radiotherapy
alone in 28 and 12%, respectively (p < 0.0004). In our retrospective study,
severe complications were found with surgery and adjuvant radiation in 36.4%,
with radiotherapy alone in 13.7% (p < 0.001). The usefulness of postoperative
radiation is not clear, and patients should not be subjected to both therapies.
Optimum candidates for primary radical surgery are women with normal ovarian
function and cervical diameters of 4 cm or smaller. Adenocarcinomas of the
uterine cervix are better treated with surgery (5-year survival 66 vs. 47%, p <
0.02).
PMID- 9658710
TI - [Intracytoplasmic injection of epididymal and testicular sperm after failed
heterologous insemination].
AB - We report on our experiences with intracytoplasmic injection (ICSI) of epididymal
and testicular spermatozoa (MESA, TESE) from azoospermic men whose wives had
previously failed to become pregnant after several cycles of artificial
insemination by donor (AID); because we do not perform AID treatment in our
clinic, all these treatments were carried out in other fertility centers as well
as the female diagnostic of sterility. In 3 husbands we could not find any
testicular spermatozoa or spermatids, leaving 15 women under treatment. Of these
15 women, 9 became pregnant. This accounts for a pregnancy rate per patient of
60%. We believe that functional defects of the oocytes and somatizing
psychological problems concerning AID are predominantly responsible for these
results and that both problems can be overcome by ICSI. Besides, these results
demonstrate that ICSI/MESA and ICSI/TESE are effective approaches in the
treatment of azoospermic men and that using cryopreserved spermatozoa is not
disadvantageous in the outcome of ICSI.
PMID- 9658711
TI - [Role of gravidin, a phospholipase A2 inhibitor, in uterine contraction].
AB - OBJECTIVE: What is the significance of gravidine, a phospholipase A2 inhibitor,
in parturition? METHODS: Gravidine concentrations were measured in amniotic fluid
obtained by transabdominal amniocentesis from women in labor at term and not in
labor using a sensitive and specific ELISA. RESULTS: (1) Amniotic fluid gravidine
concentrations were lower in the presence than in the absence of labor. (2)
Gravidine concentrations in the amniotic fluid of the forebag were higher than in
the amniotic fluid of the upper compartment. (3) There was a positive correlation
between gestational age and amniotic fluid gravidine concentrations. (4) No such
correlation could be demonstrated between cervical dilatation and amniotic fluid
gravidine concentrations. CONCLUSION: These results suggest that gravidine may
play a permissive role in the interplay with prostanoids in the mechanism of
parturition.
PMID- 9658712
TI - [Detection of endometriosis during cesarean section for HELLP syndrome in the
32nd week of pregnancy].
AB - The rare case of a decidualized endometriosis of the appendix vermiformis is
reported in a woman who developed HELLP syndrome during the 32nd week of a twin
pregnancy. Cesarean section and simultaneous appendectomy were performed. An
inspection of the appendix should always be carried out if an endometriosis
associated anamnesis is known. No pathophysiological correlations between the
HELLP syndrome and the endometriosis of the appendix vermiformis could be found.
PMID- 9658713
TI - [Obstetrics--a gear in the machinery of history].
AB - It was not Julius Caesar who was born by Caesarean section, as generally assumed,
but Scipio Cornelius Africanus, who subdued Spain 100 years before Caesar's time.
In chambers with walls of porphyrite, the Byzantine empresses used to give birth
to the heirs to the throne. In England, the infertility of Queen Anne, who
suffered from porphyria, led to the succession of the Protestant House of
Hannover following the Catholic Stuarts. Christina of Sweden, called 'queen of
baroque, rebel and scholar', was born in the 'caul'. At the age of 39 years,
Johanna of Pfirt, married to Albrecht the Lame, secured the continuation of the
Habsburg dynasty by giving birth to Rudolf the Founder. Maria Theresia, who had
16 children, was called 'mother-in-law of Europe'. She was delivered of her first
child at the age of 19. The death of her sister Maria-Anna in childbed was one of
the reasons why Gerard van Swieten was called to Vienna. Elisabeth of
Wurttemberg, first wife of Franz I of Austria, died, not as a consequence of. but
after a forceps operation carried out by Johann Lukas Boer. In England, Princess
Charlotte, daughter of George IV, and her baby son died at the delivery; Sir
Richard Croft, who had not used the forceps, committed suicide after this tragic
incident. Being the next in succession, Victoria ascended the throne. The term
'narcose au chloroforme' (first used by James Young Simpson) was changed to
'narcose a la reine' after this method had been used at the birth of Victoria's
eighth child by John Snow. It was Queen Victoria, who passed on haemophilia in
European dynasties. When Marie Louise of Habsburg had her first child, Napoleon's
son, the later Duke of Reichstadt, Antoine Dubois had to perform a turning of the
transverse presentation and use the forceps on the head following after. The
birth of Napoleon himself was a case of precipitate labour. Johann Klein, the
successor of Boer, applied the forceps when Archduchess Sophie was delivered of
her first child, the later Emperor Franz Joseph I of Austria, the first of the
four 'salt princes'. The later Emperor Wilhelm II of Prussia was delivered by
Eduard Arnold Martin the Elder, the obstetrician of Princess Victoria, the eldest
daughter of Queen Victoria; the breech presentation became even more complicated
by the raised arms of the child. Both latter monarchs had been 'asphyctic' after
their birth. Johann Wolfgang von Goethe was also among those who were apparently
dead after their birth.
PMID- 9658714
TI - [Guidelines for the management of simple ovarian cysts. A consensus report by AGO
and AGE by request of OGGG. Austrian Society of Gynecology and Obstetrics].
PMID- 9658715
TI - [40 years Austrian Society for the Study of Sterility and Fertility].
AB - The Second World Congress of the International Fertility Association (IFA) in
Naples in 1956 permitted only the participation of national fertility societies
with interdisciplinary structures: gynecology, andrology and veterinary medicine.
This short historical review shows the situation at the time of the foundation of
the Austrian Society for the Study of Sterility and Fertility regarding the
preparations as well as the members of the founding committee.
PMID- 9658716
TI - [The role of nitric oxide in reproduction].
AB - Nitrix oxide (NO) is a highly reactive and short-lived radical (half-life time:
10-12 s), which is derived from L-arginine by the NO synthases (NOS) in several
organ systems. The release of NO by endothelial cells leads to rapid relaxation
of vascular smooth muscle cells, whereas release by several neuronal cells causes
neurotransmission. When NOS is actively induced in immune cells or certain
epithelia it causes cytotoxicity and/or apoptosis of these cells. In the
reproductive organs NO is now considered to be an important trigger molecule for
several physiological mechanisms. Follicular synthesized NO is involved in
rupture of the follicle during ovulation. Moreover, NO participates in the
acrosome reaction of spermatozoa during capacitation. Apoptosis and
collagenolysis of the functional endometrium may be involved in endometrial
shedding during menstruation. Since NO induces both apoptosis and collagenolysis,
the newly discovered production of NO in late secretory endometrium could act as
a key mechanism in the process of menstrual disintegration of the endometrium.
Additionally, NO is necessary to support and maintain the decidualization process
and plays a pivotal role in implantation.
PMID- 9658717
TI - [Menstrual cycle anomalies in young girls--prognosis concerning later fertility].
AB - Menstrual disorders in adolescents should be investigated promptly to avoid or
alleviate possible long-term sequelae, including impaired fertility. Patients
with uterine amenorrhea cannot become pregnant. The prognosis for later fertility
in patients with oligoamenorrheas depends on the pathogenesis and degree of the
condition. Hypothalamic oligoamenorrheas generally resolve when the offending
stimuli are removed, and the prognosis for future fertility is good. In patients
with pituitary lesions, even those with complete loss of pituitary function,
pregnancies can be achieved and maintained with exogenous gonadotropins.
Menstrual disorders due to hyperprolactinemia can be treated effectively.
Hyperandrogenemic oligoamenorrheas, especially the polycystic ovary syndrome, are
common. Future fertility has been improved with preventive measures in
adolescence and later interventions. Patients with primary ovarian insufficiency
and persisting hypergonadotropic amenorrhea have a poor prognosis. A new aspect
is the restitution of ovarian function after treatments for malignant diseases.
PMID- 9658718
TI - [A pill for the man? Current status of fertility control in the man].
AB - Taking all facts into consideration from animal experiments and clinical studies
with regard to the development of a male contraceptive you must be aware that the
'pill for men' will hardly be available in this century. Because of the
increasing interest of the industry and the effort of the WHO and other similar
institutions, like the Population Council of New York, to develop a male pill the
stagnation of the past 20 years could be overcome, and it may be possible to have
an adequate method in 2005. In all probability this will be a combination of
hormones either from a gestagen plus testosterone preparation or a potent LHRH
agonist and/or antagonist, also in combination with a long-acting testosterone
preparation, with testosterone levels within the normal range. Nowadays it cannot
be said which role gossypol will finally play. There are studies going on with
gossypol with some promising results.
PMID- 9658719
TI - [Does the "impact factor" kill the German language?].
PMID- 9658720
TI - Effect of PEG-recombinant human megakaryocyte growth and development factor (PEG
rHuMGDF) on growth and differentiation of the HEL cell line.
AB - BACKGROUND AND OBJECTIVE: Thrombopoietin has been established as the major
regulator of megakaryocyte and platelet production. In this study we evaluated
the effects of PEG-recombinant human megakaryocyte growth and development factor
(PEG-rHuMGDF), a pegylated and truncated form of thrombopoietin, on the growth
and differentiation of the HEL cell line. As a model system we chose the
pluripotent HEL line that acquires multiple markers of the megakaryocyte/platelet
phenotype following treatment with phorbol esters, and, more importantly,
expresses the receptor for thrombopoietin (Mpl receptor) at its cellular surface.
DESIGN AND METHODS: The effect of PEG-rHuMGDF on HEL
proliferation/differentiation was evaluated in a liquid culture assay. RESULTS:
Peg-rHuMGDF do not increase the proliferative capacity of HEL cell but, in
parallel experiments, HEL cells showed a more mature and differentiated pattern
after exposure to the cytokine. Our results show that PEG-rHuMGDF, at the optimal
doses of 100-150 ng/mL, is able to induce: 1) morphological changes with the
formation of cytoplasmic protrusions; 2) increased ploidy as demonstrated by
cytofluorimetric analysis; 3) increased expression of megakaryocyte markers,
including glycoprotein IIb-IIIa and the platelet-specific alloantigen (PIA1).
INTERPRETATION AND CONCLUSIONS: These findings show that HEL cells represent a
useful model to investigate the differentiative properties of thrombopoietin in
the megakaryocyte compartment.
PMID- 9658721
TI - CD117 (c-kit) is a restricted antigen of acute myeloid leukemia and characterizes
early differentiative levels of M5 FAB subtype.
AB - BACKGROUND AND OBJECTIVE: The CD117 molecule is an antigen more frequently found
on early normal and leukemic hematopoietic cells, but its correlation with the
FAB subtypes and with other lineage and stage associated antigens is still not
well established. In this study we investigated the surface expression of CD117
antigen in 135 patients with acute leukemia in relationship to de novo or
secondary origin of AML, subtypes of FAB classification, expression of other
antigens such as CD34, HLA-DR, CD15, CD14, CD45RA, CD45RO, CD11b, CD11c, CD4,
CD7, mixed antigen co-expression (LyAg + AML and MyAg + ALL) and features of
leukemic mass. DESIGN AND METHODS: The CD117 antigen expression (clone 95C3) was
determined by flow cytometry in a series of 135 patients with acute leukemia at
diagnosis consecutively observed during the years 1995-1997: 82 AML (including 51
cases of de novo AML, 22 cases of AML following myelodysplastic syndromes (MDS),
9 cases of myeloid blastic crisis of chronic myeloid leukemia (BC-CML) and 53
ALL. All cases were stratified in CD117+ and CD117- groups and the differences
were analyzed by using appropriate statistical analyses. RESULTS: CD117 antigen
was found over 10% in 74% of AML without significant differences of positivity
between AML after MDS or BC-CML and de novo AML. We did not note a significant
correlation between FAB classification and CD117 which was expressed in 100% of
M1 and M7 cases, in 80% of M0 cases, in 75% of M2 cases, in 70% of M3 cases and
in 82% of M4 cases. Instead, in M5 subtype CD117 was strictly restricted to
earlier stages: ten of the eleven M5b (91%) cases completely lacked CD117 antigen
expression, whereas 100% of M5a cases were positive. The results of Pearson's
coefficient showed: 1) a significant inverse relationship between CD117 and CD15,
CD4 and CD14 (only in M5 subtypes) and CD11b, CD11c and CD45RO (in all cases); 2)
a significant direct correlation between CD117 and CD34 and CD45RA (in all
cases); and 3) an independent expression between CD117 and CD15 associated with a
low correlation between CD117 and HLA-DR antigen (only in non-monocytic cases).
In ALL, whether of B or T lineages, surface expression of CD117 was never
observed. INTERPRETATION AND CONCLUSIONS: We conclude that the CD117 antigen
shows a high specificity for AML, independently upon FAB classification, and
represents a reliable marker in characterizing the differentiative degree of the
monocytic blasts.
PMID- 9658722
TI - CD27 in B-cell chronic lymphocytic leukemia. Cellular expression, serum release
and correlation with other soluble molecules belonging to nerve growth factor
receptors (NGFr) superfamily.
AB - BACKGROUND AND OBJECTIVE: CD27, a transmembrane homodimer belonging to the nerve
growth factor (NGF) receptor superfamily, is typically expressed on leukemic CD5+
cells in B-cell chronic lymphocytic leukemia (CLL) and found in soluble form in
the serum of CLL patients. Therefore, we investigated clinico-biological
implications of increased serum levels of sCD27 in an unselected series of B-CLL
patients. DESIGN AND METHODS: Serum CD27 (sCD27) levels were determined at the
time of diagnosis in 82 previously untreated B-CLL patients using a sandwich
enzyme-linked immunoassay (ELISA). Results were correlated with either clinico
hematological or biological features. Finally, quantitative flow cytometric
analyses of membrane CD27 (mCD27) expression were carried out on peripheral blood
(PB) cells of 22 B-CLL patients and 5 healthy controls, respectively. RESULTS:
CD27 was found to be expressed on the surface of both resting normal and leukemic
B cells. sCD27 levels were significantly higher in B-CLL patients (median value
2150 U/mL) than in healthy controls (median value 220 U/mL) (p < 0.0001). There
was a close relationship between sCD27 and soluble TNF-alpha, another molecule
belonging to the NGF receptor superfamily. Changes in sCD27 level correlated with
clinical stage, beta 2 microglobulin and LDH. INTERPRETATION AND CONCLUSIONS:
These findings indicate that sCD27 is a reliable marker of tumor mass in B-CLL.
Its potential prognostic value should be tested in prospective studies.
PMID- 9658723
TI - Microsatellite analysis in childhood acute lymphoblastic leukemia.
AB - BACKGROUND AND OBJECTIVE: Genetic alterations, including genomic instability,
represent possible steps towards a malignant transformation. One approach to
delineate replication errors in cancer cells is to determine alterations of
microsatellites that are short tandem repeat sequences dispersed throughout the
human genome. We have investigated whether genomic instability may be a possible
event in the leukemogenic process by evaluating the pattern of instability in 41
cases of childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS:
Eighty-two samples of genomic DNA (41 at diagnosis and 41 at remission) were
analyzed by PCR with microsatellite markers chosen on five different chromosomes
(2, 10, 11, 13, 18) known to be frequently involved in tumors of various origins.
Since deletions of the short arm of chromosome 12 are relatively common in
children with ALL, we also analyzed one region flanked by the microsatellite
marker D12S308 on 12p. This area encompasses a genetic locus which contains the
putative suppressor gene KIP1. RESULTS: A pattern of MI at one or two loci on
different chromosomes could be documented in 4 of the 41 cases analyzed (9.7%).
Three were common ALL and 1 was a T-ALL. One case showed two concomitant sites of
instability, while 1 revealed two additional bands by using simultaneously
microsatellite markers D2S123 and D18S58. INTERPRETATION AND CONCLUSIONS: These
results indicate that genetic instability of microsatellite repeat sequences
occurs in a proportion of childhood ALL. Mismatched repair errors documented in
hereditary and sporadic solid tumors may thus be involved in hematological
malignancies. While in such cases the pattern of genomic instability appears
indicative of a mutator phenotype and of a potential predisposition towards a
leukemic transformation, other genomic loci close to cytogenetic and molecular
alterations known to occur in ALL need to be investigated in depth in cases with
an apparently non mutated phenotype.
PMID- 9658724
TI - Conventional cytogenetics and FISH evaluation of chimerism after sex-mismatched
bone marrow transplantation (BMT) and donor leukocyte infusion (DLI).
AB - BACKGROUND AND OBJECTIVES: Sensitive and quantitative cytogenetic methods to
better assess the biological significance of post-BMT chimerism have been
recently developed. In this study, we compared the results of chimerism analysis
and evolution employing conventional cytogenetics and fluorescence in situ
hybridization (FISH) in 16 patients after sex-mismatched BMT, and in 5 patients
after donor lymphocyte infusion (DLI) to treat post-BMT relapse. DESIGN AND
METHODS: FISH studies were performed using separate digoxigenin labeled
centromeric DNA probes for the X (pDMX1) and Y (DYZ1/DYZ3) chromosomes. To this
purpose, different types of samples were used: bone marrow (BM) and peripheral
blood (PB) slides processed for conventional cytogenetics, and routine BM and PB
smears. RESULTS: Results of chimerism studies performed on different types of
samples showed no significant differences. No significant differences in the
ability to identify the sex of each cell with both pDMX1 and DYZ1/DYZ3 probes
were found and the results obtained from independent experiments showed a high
linear correlation. Chimerism analysis by FISH showed initial mixed chimerism
after BMT in 10 patients. Seven of these patients were also studied by
conventional cytogenetics and 2 of these showed mixed chimerism. Seven of the
former 10 patients evolved to complete donor chimera. 6 patients showed
cytogenetic or hematologic bone marrow relapse, 3 of which were preceded by mixed
chimaerism as revealed by FISH studies. FISH studies permitted an easy and
accurate monitorization of the response to DLI in 5 relapsed patients, showing an
increase in the proportion of donor cells in 4 patients as they reached a new
complete remission. INTERPRETATION AND CONCLUSIONS: Both FISH and conventional
cytogenetics are quantitative methods to assess chimerism. However, FISH is more
sensitive, accurate and can even be applied on routine BM and PB smears.
Furthermore, its combination with immunophenotyping approaches to quantify
chimerism on cell subpopulations, will help to clarify post-BMT chimerism
significance.
PMID- 9658725
TI - Renal complications in acute leukemias.
AB - BACKGROUND AND OBJECTIVE: Renal failure is a known complication of acute
leukemias both at diagnosis and following cytostatic treatment. No recent studies
give data on the incidence and risk factors of renal complications and their
prognostic impact. DESIGN AND METHODS: Two hundred and twenty consecutive adult
patients with newly diagnosed acute leukemia treated at a major university
medical center were evaluated for renal complications before, during, and after
treatment; 166 patients were treated by chemotherapy only and 54 patients were
treated with chemotherapy and later transplanted with allogeneic or autologous
bone marrow. Renal complications were subdivided into 3 entities: acute renal
failure, major and minor complications, based on clinical and laboratory
parameters. Renal failure occurring as a consequence of terminal multi-organ
failure was excluded from the present study. RESULTS: Approximately 30% of
patients in the chemotherapy group had a renal complication either before or
after chemotherapy. Patients undergoing transplantation had a 50% risk of renal
complications. Risk factors for complications were male sex, age, previous kidney
disease, white cell count, and refractory leukemia (chemotherapy group) and
allogeneic versus autologous transplant (transplant group). In the chemotherapy
group, early but not delayed renal complications had a poor prognostic impact. In
the transplant group renal complications had no impact on prognosis. In all
patient groups, acute renal failure was prognostically unfavorable.
INTERPRETATION AND CONCLUSIONS: We conclude from our study that renal
complications are frequent in acute leukemias and that the treatment and
prevention of renal complications is important for the management of acute
leukemias.
PMID- 9658726
TI - A new combination of carboplatin, high-dose cytarabine and cross-over
mitoxantrone or idarubicin for refractory and relapsed acute myeloid leukemia.
AB - BACKGROUND AND OBJECTIVE: High-dose cytarabine (HIDAC) and new anthracycline-type
drugs (mitoxantrone, idarubicin) are the mainstay of several active regimens
against relapsed and refractory acute myeloid leukemia (AML). The present study
was undertaken to assess the feasibility, toxicity, and antileukemic activity of
carboplatin (CBDCA) added to a combination of the two former agents. DESIGN AND
METHODS: Two regimens (R) of CBDCA plus HIDAC and either mitoxantrone or
idarubicin (crossover) were sequentially evaluated. R-1 consisted of CBDCA 300
mg/m2/d (24-hour infusion) on days 1-4, HIDAC 1 g/m2/bd on days 1-5, and
mitoxantrone/idarubicin 12/6 mg/m2/d on days 1-3, followed by granulocyte colony
stimulating factor (G-CSF). R-2, an attenuated-toxicity regimen, consisted of
CBDCA and G-CSF as above, HIDAC on alternate days (1, 3, 5), and
mitoxantrone/idarubicin 8/5 mg/m2/dose. Intended post-remission therapy included
a similar, lower intensity course and a myeloablative phase supported by an
allogeneic or autologous blood cell transplant. RESULTS: Twenty-nine patients
(median age 53 years, one child) formed the study group: 10 (34%) had a primary
refractory disease (8 to idarubicin-cytarabine-etoposide, ICE), 6 (21%) were at
second or subsequent relapse, and 5 (17%) had a first remission lasting < 12
months. In addition, 4 patients (14%) had received prior HIDAC and 10 (34%) were
relapsing after a bone marrow/blood cell transplant. Twelve patients were treated
with R-1 and 17 with R-2. The complete response rate was 25% with R-1 and 53%
with R-2, due to a significantly lower death rate by pancytopenic complications
(p = 0.023). The probability of response by risk class was: primary refractory
30% (43% with R-2), > 2nd relapse 33% (50% with R-2), 1st relapse < 12 months 40%
(50% with R-2), 1st relapse > 12 months 50% (75% with R-2), prior HIDAC 75%, and
prior transplant 30% (33% with R-2). Seven patients could undergo an autologous
(n = 5) or allogeneic (n = 2) bone marrow/peripheral blood cell transplant after
one consolidation cycle. Overall survival was 4.2 months, significantly longer in
responders (complete and partial: median 11 months) than non-responders (p <
0.001). Median duration of complete remission was 10 months and 2-year
probability 0.31, but no patient remained disease-free at 3 years. INTERPRETATION
AND CONCLUSIONS: R-2 was well tolerated, exerted a significant activity in high
risk AML, and is amenable to further improvements. However, the lack of long-term
disease-free survivors indicates the need for innovative post-remission
strategies.
PMID- 9658728
TI - Use of recombinant granulocyte colony-stimulating factor in Fanconi's anemia.
AB - BACKGROUND AND OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) has been
shown to improve the neutropenic status of patients with bone marrow failure. The
side effects in prolonged treatment still need to be determined. DESIGN AND
METHODS: We have studied the efficacy and the long-term side effects of G-CSF in
four patients with Fanconi's anemia and severe neutropenia. RESULTS: Three
patients responded with an increase in their absolute neutrophil count; neither
improvement in platelet count and hemoglobin concentration nor effect on
transfusion requirements was seen. CFU-GM and BFU-E were undetectable before,
during and after treatment. Responders showed an important reduction in number
and severity of infections, with a marked improvement of clinical status. The
fourth patient developed acute myeloid leukemia after 4 weeks of G-CSF treatment.
During maintenance, one patient was treated with G-CSF for 18 months, until she
received bone marrow transplantation, without presenting side effects. In the
second responding patient G-CSF treatment was stopped because of appearance of
immature cells in peripheral blood and myeloid blasts in bone marrow. The third
responding patient presented immature peripheral myeloid cells during the third
year of G-CSF treatment: disappearance of immature cells was observed after G-CSF
reduction. In two cases FISH analysis revealed monosomy 7 after G-CSF treatment.
INTERPRETATION AND CONCLUSIONS: G-CSF use results in an improvement of clinical
status, but long term administration may cause adverse experiences and requires a
close hematological monitoring.
PMID- 9658727
TI - Collection of peripheral blood progenitor cells for autografting with low-dose
cyclophosphamide plus granulocyte colony-stimulating factor.
AB - BACKGROUND AND OBJECTIVE: The combination of high or intermediate-dose
cyclophosphamide (CY) plus granulocyte colony-stimulating factor (G-CSF) is
useful to mobilize hematopoietic progenitor cells to peripheral blood, but the
patients require hospitalization. The aim of this study was to evaluate the
efficiency of low-dose CY plus G-CSF (5 ug/kg/day s.c.) as an outpatient
treatment in order to collect enough progenitor cells for hematopoietic rescue in
autologous peripheral blood transplantation (APBSCT). DESIGN AND METHODS: We
analyzed twenty-eight consecutively treated patients with lymphoma or multiple
myeloma. The number of CD34+ cells in blood samples was determined from day +7.
Leukapheresis (LKP) began when the absolute number of CD34+ cells in peripheral
blood was > 2500/mL and the apheresis product was assayed for mononuclear cells
(MNC), granulocyte-macrophage colony-forming units (CFU-GM), total nucleated
cells (tNC) and CD34+ cells. RESULTS: Twenty-eight outpatients with advanced
hematologic malignancies (13 non-Hodgkin lymphoma, NHL; 10 Hodgkin's disease, HD;
and 5 multiple myeloma, MM), median age 44 years (range 23-65) received a single
dose of CY (1.5 g/m2 i.v. day 0) followed by G-CSF (5 ug/kg/day s.c.) from day +1
to the end of LKP. Considering patients who had successful mobilization (64%), a
median of 7.1 x 10(6)/kg CD34+ cells (range 3.5-11.9), 5.7 x 10(5)/kg CFU-GM
(range 1.5-9.2), 4.4 x 10(8)/kg MNC (range 1.9-7.9) were collected. Treatment was
well tolerated and none of these patients was hospitalized due to neutropenic
fever. Only one patient received two packed red blood cells following
chemotherapy. Autologous peripheral blood stem cell transplantation (APBSCT) has
been performed in 18 patients (64%). The mean number of days to achieve > 0.5 x
10(9) PMN/L and > 20 x 10(9) PLT/L was 12 (10-17) and 12.6 (8-24), respectively.
INTERPRETATION AND CONCLUSIONS: Considering a pre-established threshold of 2.5 x
10(6)/kg CD34+ cells to proceed to APBSCT, the mobilization therapy was
successful in 64% of the patients but was unsuccessful in 10 patients (5 NHL, 4
HD and 1 MM). Hematopoietic recovery was complete and stable in all patients. Low
dose CY plus G-CSF is efficient to collect enough PBSC for hematopoietic rescue
after myeloablative therapy in patients with lymphoprolipherative disorders or
multiple myeloma.
PMID- 9658729
TI - Home treatment of deep vein thrombosis: a two-years experience of a single
institution.
AB - BACKGROUND AND OBJECTIVE: Low molecular weight heparin (LMWH) is known to be safe
and effective for the initial treatment of patients with acute deep-vein
thrombosis (DVT). Moreover, LMWH allows patients to be treated at home. However,
only limited data are available on the feasibility of LMWH treatment at home in
daily clinical practice. DESIGN AND METHODS: We evaluated the feasibility,
efficacy and safety of home treatment of DVT in a consecutive series of
outpatients using LMWH over a two year period. The two main reasons for exclusion
were concomitant pulmonary embolism and a high hemorrhagic risk. Patients were
treated with 95 IU/kg bid of nadroparin for a minimum of 7 days. The study design
allowed patients to go home immediately after diagnosis or to be discharged after
a short hospital stay. Anticoagulation with acenocoumarol was started 2 days
before discontinuing nadroparin. RESULTS: From 1995 to 1997, 71 consecutive
outpatients with DVT were treated with nadroparin. Ambulatory treatment was
feasible in 39 patients (24 patients did not require admission and 15 patients
were discharged in less than 48 hours). The remaining 32 patients were treated in
hospital. The main causes for admission were the presence of serious comorbid
conditions, the severity of symptoms in the involved leg and the inability to
obtain a diagnosis. None of the patients had clinical recurrent venous
thromboembolism during the initial treatment with nadroparin. One patient
receiving nadroparin at home had a non-fatal major bleeding. None of the patients
to whom the possibility of home therapy was offered wished to remain at hospital.
However, only 26% of the home-treated patients injected the drug by themselves.
INTERPRETATION AND CONCLUSIONS: Home therapy of DVT with LMWH bid at doses
adjusted to patient's body weight is feasible, efficient and safe. Over 50% of
outpatients with DVT can be treated at home, either entirely or after a short
stay in hospital. Nevertheless, before using this therapeutic alternative as a
standard of practice, an adequate assessment of embolic and hemorrhagic risks,
and comorbid conditions, should be made.
PMID- 9658730
TI - Prevalence and patterns of symptomatic thromboembolism in oncohematology.
AB - BACKGROUND AND OBJECTIVE: Approximately 15% of patients with cancer will
experience a thrombotic episode at some time. Some patients are at particularly
high risk depending on the histology of the malignant disease. The aim of the
study was to determine the actual prevalence of thrombotic episodes in
oncohematologic patients. DESIGN AND METHODS: We conducted a retrospective cohort
analysis on a total of 515 patients that were admitted to the out-patients clinic
(Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two
main groups were selected for this study: 133 patients suffering from a
myeloproliferative disorder and 382 patients affected by a lymphoproliferative
disorder. Follow-up lasted a median of 33 months in both groups (range 3-144
months). The difference between the observed events for each group was estimated
by the odds ratio and chi square. Age and sex distribution were estimated by the
Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan
Meier method and compared between groups (DVT patients and non DVT patients) by
the log-rank test. RESULTS: Twenty-three patients experienced a venous thrombotic
disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and
lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively
(odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was
apparently idiopathic in 17 cases. In 4 patients another cancer was present; in
the remaining 2 patients the thrombotic episode was associated with other
predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find
any difference in the overall survival compared to oncohematologic patients who
did not experience DVT. INTERPRETATION AND CONCLUSIONS: The prevalence of
symptomatic DVT in the oncohematological patients is lower than reported for
solid tumor. Patients affected by myeloproliferative disease have a higher risk
of developing thrombosis. DVT if well-treated does not influence the survival of
oncohematological patients.
PMID- 9658731
TI - Classification and diagnosis of iron overload.
AB - BACKGROUND AND OBJECTIVE: Iron overload is the result of many disorders and could
lead to the development of organ damage and increased mortality. The recent
description of new conditions associated with iron overload and the
identification of the genetic defect of hereditary hemochromatosis prompted us to
review this subject and to redefine the diagnostic criteria of iron overload
disorders. EVIDENCE AND INFORMATION SOURCES: The material examined in the present
review includes articles published in the Journals covered by the Science
Citation Index and Medline. The author has been working in the field of iron
overload diseases for several years and has contributed ten of the papers cited
in the references. STATE OF THE ART AND PERSPECTIVES: Iron overload can be
classified on the basis of different criteria: route of access of iron within the
organism, predominant tissue site of iron accumulation and cause of the overload.
Excess iron can gain access by the enteral route, the parenteral route, and
placental route during fetal life. The different distribution of iron within
parenchymal or reticuloendothelial storage areas indicates different pathogenetic
mechanisms of iron accumulation and has relevant implications in terms of organ
damage and prognosis of the patients. Iron overload may be either primary,
resulting from a deregulation of intestinal iron absorption as in hemochromatosis
or secondary to other congenital or acquired conditions. Diagnosis of iron
overload can be suspected on the basis of clinical data, high transferrin
saturation and/or serum ferritin values. However, several hyperferritinemic
conditions are not related to iron overload, but may imply severe disorders
(inflammations, neoplasia) or a deregulation of ferritin synthesis (hereditary
hyperferritinemia-cataract syndrome), and iron overload secondary to
aceruloplasminemia, and the recently described dysmetabolic-associated liver iron
overload syndrome, are characterized by low or normal transferrin saturation
levels. Liver biopsy is still very useful in the diagnostic approach to iron
overload disorders, by defining the amount and the distribution of iron within
the liver. The analysis of HFE gene mutations (C282Y and H63D) is a simple and
strong tool in the diagnostic work out of iron overload conditions.
PMID- 9658732
TI - Molecular genetics and control of iron metabolism in hemochromatosis.
AB - BACKGROUND AND OBJECTIVES: Hereditary hemochromatosis (HC) is an inborn error of
iron metabolism that leads to progressive iron overload. Considerable advances in
the knowledge of molecular events in iron metabolism have been recently obtained.
These molecular findings, the cloning of the gene responsible for HC (HFE gene)
and the results of preliminary studies on the HFE protein prompted us to review
this topic. INFORMATION SOURCES: The material examined in this review article
includes papers and abstracts published in the Journals covered by the Science
Citation Index and Medline. The authors have been working in the field of HC for
several years and have contributed eleven of the quoted papers. STATE OF ART AND
PERSPECTIVE: HC is now recognized as the genetic disease characterized by the
homozygosity for the Cys-->Tyr substitution at position 282 (C282Y) of the HFE
protein. The mutation abolishes the association of the HFE protein with beta 2
microglobulin (beta 2M), making the complex unable to gain the cell surface. Thus
HC is an example of abnormal trafficking of the corresponding proteins. It is
clear by the analysis of its structure that HFE protein is not an iron
transporter itself, but has a regulatory role in iron metabolism. Its peculiar
localization in the crypt cells of the small intestine suggests an important role
in iron trafficking at this level. However, other proteins are involved in iron
uptake, as the recently cloned Nramp2, the first iron transporter discovered in
mammalians. Nramp2 has a recognized role both in the intestinal iron uptake and
in the iron transport within the erythroblast. The relationships between HFE and
Nramp2 are still unexplored. The recent association of HFE gene with transferrin
receptor (TfR) in trophoblast cells opens new possibilities on its role in
cellular iron uptake. The existence of other forms of genetic iron overload
suggests that the scenario of iron proteins is not yet fully defined. Further
studies in this field will contribute to our knowledge of iron metabolism
regulation in humans.
PMID- 9658733
TI - Human herpesvirus-8 in hematological diseases.
AB - The huge amount of experimental and clinical observations supporting the possible
involvement of human herpesvirus 8 (HHV-8) or Kaposi sarcoma herpesvirus (KSHV)
in human lymphoproliferative diseases was critically reviewed during a workshop
organized by the Italian Society for Experimental Hematology in Florence, Italy,
on July 3rd, 1997. The organizers have prepared this report for the readers of
Haematologica.
PMID- 9658734
TI - T-cell acute lymphoblastic leukemia occurring in a patient with acute
promyelocytic leukemia.
AB - Secondary acute lymphoblastic leukemia (sALL) following acute myeloid leukemia
(AML) is a rare event; only eight cases have been reported. We report a patient
with acute promyelocytic leukemia (APL), in hematological and molecular remission
who developed T-ALL three years after the diagnosis of APL. The morphological,
cytochemical, phenotypical and molecular features of this T-ALL were different
from those of the previous APL. The absence of t(15;17), negative PML/RAR alpha
at reverse transcription polymerase chain reaction (RT-PCR) analysis and presence
of TcR delta support the hypothesis that the T-ALL in this sALL case originated
from a different clone from that of the APL cells.
PMID- 9658735
TI - The magic of immersion oil: gray platelet syndrome.
PMID- 9658736
TI - The number of nucleoli expressed by the nucleolar coefficient in the
granulopoietic bone marrow compartment in non-leukemic persons and patients
suffering from chronic myeloid leukemia.
PMID- 9658737
TI - Autologous stem cell transplantation in multiple myeloma: a single center
experience.
AB - This study shows the feasibility and safety of autologous stem cell
transplantation in 32 of 98 multiple myeloma patients referred to our institution
over a 3-year period. Complete response rate was 19% and partial response rate
58%. A significantly better outcome was shown among newly diagnosed patients in
comparison with pretreated patients.
PMID- 9658738
TI - Enzyme replacement therapy decreases hypergammaglobulinemia in Gaucher's disease.
AB - We report the effects of enzyme replacement therapy in a patient with Gaucher's
disease associated with a monoclonal gammopathy. Alglucerase induces a linear
decline in immunoglobulin and beta 2-microglobulin levels. This observation
suggests that this treatment decreases the chronic antigenic stimulation commonly
found in Gaucher's disease.
PMID- 9658739
TI - The standard of disclosure in human subject experimentation.
PMID- 9658740
TI - Criminalization of perinatal HIV transmission.
PMID- 9658741
TI - Improper expert medical testimony. Existing and proposed mechanisms of oversight.
PMID- 9658742
TI - Medicinal use of marijuana. Is the debate a smoke screen for movement toward
legalization?
PMID- 9658743
TI - Evaluation of pancreatic exocrine function and zinc absorption in alcoholism.
AB - Zinc absorption in alcoholism was studied by a combination of zinc tolerance
tests in 382 male patients with alcoholism (more than 140 g/day of ethanol) who
had alcohol-induced disease of the liver or pancreas. In study 1, the serum zinc
level was measured in all patients, and serum zinc and fecal chymotrypsin levels
were compared in various disease groups. In study 2, 14 patients with liver
cirrhosis (LC), 15 with chronic pancreatitis (CP), 7 with LC + CP, and 7 controls
underwent oral zinc tolerance and zinc dipicolinate tolerance tests, zinc
absorption and disorders of pancreatic exocrine functions were examined. In study
1, the serum zinc concentration was significantly lower in the CP and LC groups
than in the control group, and the fecal chymotrypsin activity was significantly
lower in the CP than in the control groups. In study 2, during the oral zinc
tolerance test, the serum zinc concentration 3 hours after administration was
significantly lower in the LC, CP and LC + CP groups than in the control group.
In these groups, the serum zinc concentration was significantly lower in the
abnormal fecal chymotrypsin group than in the control group at 2 and 3 hours
after administration of zinc sulfate. In the oral zinc dipicolinate tolerance
test, the serum zinc levels 2 and 3 hours after administration were significantly
elevated in the control and all disease groups; there were no significant
differences between the control and each disease group. These results suggest
that reduction of pancreatic exocrine functions by alcohol and chronic reduction
of synthesis of ligands such as picolinic acid in the liver are involved in the
reduction of serum zinc in alcoholism.
PMID- 9658744
TI - Cyfra 21-1 as a marker of lung cancer.
AB - The utility of cytokeratin fragment (Cyfra) 21-1, a new tumor marker, was
investigated in 100 patients with lung cancer. Sandwich enzyme immunoassay
detected Cyfra 21-1 in the sera of 60% of patients. Sensitivity of this marker
was especially high (86.4%) for squamous cell carcinoma, exceeding that of a
similar marker, squamous cell carcinoma antigen (SCC, 54.5%). In contrast,
sensitivity of Cyfra 21-1 was relatively low for adenocarcinoma (52.6%) and for
small cell carcinoma (50%). We conclude that Cyfra 21-1 is of value in diagnosis
of lung cancer, particularly squamous cell carcinoma.
PMID- 9658745
TI - Type IV collagen and laminin enhance the motility, adhesion, and proliferation of
hepatoma cells.
AB - Type IV collagen and laminin, major components of the basement membrane, are
involved in several biologic activities. In malignant tumors, cell-matrix
interactions are very important for tumor invasion and metastasis. In
hepatocellular carcinoma, these matrices are present around hepatoma cells.
However, there is little known how these matrices influence on the behavior of
hepatoma cells. In this study, we investigated the participation of type IV
collagen and laminin in the motility, adhesion, and proliferation of hepatoma
cells using three different human hepatoma cell lines (KYN-1, 2, 3). The
production of type IV collagen and laminin was investigated by immunoelectron
microscopy. The effects of type IV collagen and laminin on hepatoma cell
migration, adhesion, and proliferation were evaluated by the haptotactic
migration assay, phagokinetic track assay, an adhesion assay, and a 3H-thymidine
incorporation assay. Immunoelectron microscopy showed the production of type IV
collagen and laminin by hepatoma cells. Type IV collagen and laminin enhanced
haptotactic migration, chemokinesis, adhesion, and thymidine incorporation by
hepatoma cells. The combination of type IV collagen and laminin had the most
pronounced effects on these biologic activities. These results indicate that type
IV collagen and laminin promote hepatoma cell motility, adhesion, and
proliferation in an autocrine manner, suggesting enhancement of invasion and
metastasis of hepatoma cells by these basement membrane components in vivo.
PMID- 9658746
TI - EMG analysis of the lower extremities during pitching in high-school baseball.
AB - I evaluated the contractions of the muscles of the lower extremities during
baseball pitching using video imaging and simultaneous surface EMG. The subjects
were 10 members of a high school baseball club and, for contrast, 10 students
without any baseball club experience. I divided their pitching movements into two
phases determined with respect to the landing of the non-pivot leg. The EMG
signal intensities over the 2 seconds prior to landing, and over the 2 seconds
after landing, were then integrated to give an EMG value to each phase. I then
computed this value as the % MMT. The abductor and adductor of the hip muscles of
both lower extremities in the players were strongly contracted, especially the
adductor. This finding was consistent with the observation that pitching tends to
lead to adductor muscle disorders. Strengthening the adductor and its antagonist
abductor can therefore directly influence the capability for pitching, and can
reduce the risk for the adductor disorders.
PMID- 9658747
TI - Induction of apoptosis in ovarian carcinoma cell line by gonadotropin-releasing
hormone agonist.
AB - Gonadotropin releasing hormone (GnRH) agonist suppresses the growth of the cancer
cells in vitro. To evaluate the effect of a GnRH agonist (GnRHA) in ovarian
carcinomas, we investigated the interactions of GnRHA with the KOC-2s human
ovarian cancer cells. The addition of GnRHA (10(-8)-10(-6)M) produced an increase
20-30% in the number of cells (p < 0.05). GnRHA (10(-5) M) produced a slight,
statistically insignificant decrease of < 10% in the cell count. No DNA
fragmentation was produced by GnRHA (10(-8)-10(-6)M). However, GnRHA (10(-5)M)
produced internucleosomal cleavage of DNA into fragments with multiples of 180 to
200 bp. This DNA "ladder" pattern is characteristic of apoptosis. The amount of
Fas antigen was reduced by each concentration of GnRHa. The addition of GnRHA
(10(-6)M and 10(-5)M) significantly increased the secretion of TNF-alpha (p <
0.001). The time- and dose-dependent effects of GnRHA might be confined to the
KOC-2s cells as demonstrated by growth inhibitions and characteristic
internucleosomal DNA fragmentation. However, the effects of GnRHA on secretion of
TNF-alpha and the expression of Fas antigen differed. The present results provide
a basis for future studies on the mechanism of apoptotic effect of GnRHA.
PMID- 9658748
TI - Increased circulating levels of interleukin-1 receptor antagonist in patients
with inflammatory bowel disease.
AB - Plasma levels of interleukin-1 receptor antagonist (IL-1ra), a potent inhibitor
of IL-1, were measured in patients with inflammatory bowel disease. Plasma IL-1ra
levels in patients with active ulcerative colitis and Crohn's disease were higher
than in normal controls. No significant difference was noted in plasma IL-1ra
concentrations between active ulcerative colitis and Crohn's disease patients.
The levels in patients with inactive disease were lower than in active patients,
but were higher than in normal controls. Plasma IL-1ra levels correlated
significantly with clinical disease activity and laboratory parameters such as C
reactive protein or leukocyte count. In conclusion, circulating IL-1ra in
patients with inflammatory bowel disease may be a useful marker of disease
activity.
PMID- 9658749
TI - Negative-strand HCV RNA was not detected in bone marrow cells of patients with
HCV infection.
AB - To determine whether hepatitis C virus (HCV) replicates in bone marrow, we
investigated positive- and negative-strand HCV RNA in bone marrow cells and
fluids, and sera from patients with HCV infection. The study population consisted
of 15 patients positive for antibodies to HCV (anti-HCV). Positive- and negative
strands HCV RNA were detected using highly strand-specific rTth reverse
transcription-polymerase chain reaction (rTth RT-PCR) followed by Southern
blotting analysis. Positive-strand HCV RNA was detected in 12 (80%) serum
samples, in 13 (86.7%) bone marrow fluid specimens, and in 6 (40.0%) bone marrow
cell samples. Negative-strand HCV RNA was detected in 9 (60.0%) serum samples, 11
(91.7%) fluid specimens, while it was not detected in bone marrow cells. The
absence of negative-strand HCV RNA in bone marrow cells suggested that HCV does
not replicate in these cells. Negative-strand HCV RNA detected in serum and bone
marrow fluid samples may have been due to contamination with circulating HCV RNA
from hepatocytes.
PMID- 9658750
TI - Effect of laser irradiation for residual lesions of early gastric carcinoma after
endoscopic mucosal resection.
AB - Endoscopic mucosal resection (EMR) for mucosal gastric carcinoma without lymph
node metastases has been widely accepted as a curative procedure in Japan. We
consider patients with elevated type well-differentiated adenocarcinoma less than
20 mm in size, as well as those with depressed type intramucosal carcinoma
without ulcer and less than 10 mm in size, to be absolute indications for
treatment by EMR. In this study, we evaluated 26 patients (68.4 +/- 9.7 yrs) with
absolute adaptive lesions who underwent EMR as an initial treatment, resulting in
incomplete resection of lesions. We performed laser therapy on patients with
residual lesions, and examined the effects of this treatment. Eighteen cases with
elevated type lesions (90%) have not exhibited recurring lesions treated by
initial laser therapy alone following EMR over a period of 24 months. However,
among patients with depressed type lesions, only 1 (16.7%) did not experience
recurrence. There was a significant difference between the two groups (p <
0.001). These recurring lesions were treated by additional laser therapy. The
results were more satisfactory in patients with elevated type lesions (95.5%)
than in patients with depressed type lesions (80%). No patient died of gastric
cancer during follow-up. Endoscopic laser irradiation is useful in treating
patients with residual lesions after EMR.
PMID- 9658751
TI - Microsurgical management of craniopharyngiomas--outcomes in 56 patients.
AB - Fifty-six patients with craniopharyngiomas were operated by microsurgical
techniques during a 20-year period. Of the 56 patients, 28 were males and 28 were
females, with a mean age of 33 years (range 1 to 78 years). Twenty patients
(35.7%) were less than 15 years of age. Remission was defined as clinical
improvement with stable ophthalmological and neurological status, CT and/or MRI
evidence of a decrease in tumor size or tumor disappearance when a patient was
discharged from hospital. Ineffectiveness was defined as lack of change in the
preoperative clinical status. The mean follow-up period in this study was 6.9
years, with 11 patients monitored. The most common presentation was visual
dysfunction (69.6%). 33.9% of the patients presented with headache. The most
frequent preoperative finding was a visual field defect, with 55.4% of the
patients so affected; 39.5% of patients had preoperative hypothyroidism and 40%
had hypoadrenalism. Diabetes insipidus was found preoperatively in 7.1%. Three
female patients had amenorrhea. Hydrocephalus was uncommon, being present in only
10.7%. Unruptured aneurysms were found incidentally in 2 cases. A pterional
approach was used in 29 patients (52%), a transcallosal approach in 13 (23%), a
transcortical approach and a transsphenoidal approaches in 3 (5%), and a lamina
terminalis approach in 1 patient. Multiple procedures were required in 8 patients
in order to provide significant relief of compressive symptomatology. Overall,
12.5% of the tumors were completely resected. 92.9% of our patients were in
remission, 2 had ineffectiveness result, and 2 died of postoperative
complications. Except for the completely resected cases, all the other patients
underwent radiotherapy postoperatively. The results of this series show that
microsurgical management of craniopharyngiomas yields good operative results.
PMID- 9658752
TI - Changes of visual performance induced by exposure to whole-body vibration.
AB - To clarify the effects of whole-body vibration (WBV) on visual performance,
visual acuity and a self-rated assessment of difficulties in visible perception
were determined after various frequencies of vibration in six healthy males. Two
different sitting postures, an erect posture and a muscle-relaxed posture, were
used. Sinusoidal vertical vibrations at ten frequencies (8, 10, 12.5, 16, 20, 25,
31.5, 40, 63.5 and 80 Hz) were applied to the seated subjects for 20 sec. The
magnitude of acceleration at each vibration frequency was maintained at 2.5 msec
2 (r.m.s.). The visual performance was evaluated by a standard visual acuity test
and a self-rated assessment for difficulties in visible perception. The
disturbances of visual performance were dependent on the vibration frequency (p <
0.01, ANOVA) with a maximum reduction of visual acuity at a frequency of 12.5 Hz.
The disruption of the visual performance was more severe with the erect posture
than with the muscle-relaxed posture. In conclusion, short-term WBV exposure can
affect visual performance, depending on the vibration frequency and the sitting
posture. The visual acuity and self-rated assessment of disturbances of vision
may be influenced by the resonance frequency of the eyeball.
PMID- 9658753
TI - Therapeutic implications of interleukin-10 in inflammatory bowel disease.
AB - Enhanced production of proinflammatory cytokines has been described in
inflammatory bowel disease. The effect of interleukin (IL)-10, a cytokine with
antiinflammatory activity, or anti-IL-10, on cytokine production by cultured
colonic mucosa or blood mononuclear cells from patients with active inflammatory
bowel disease was evaluated. Addition of IL-10 to the culture medium of colonic
tissues or blood mononuclear cells resulted in inhibition of both IL-1 beta and
tumor necrosis factor-alpha production and augmentation of IL-1 receptor
antagonist production. Conversely, neutralization of endogenous IL-10 was found
to augment both tumor necrosis factor-alpha and IL-1 beta production and inhibit
IL-1 receptor antagonist production. In addition, the production of IL-10 by
mononuclear cells was suppressed by prednisolone. In conclusion, IL-10 and
related molecules may be useful in the treatment of inflammatory bowel disease.
PMID- 9658754
TI - Myeloperoxidase concentrations in the stool as a new parameter of inflammatory
bowel disease.
AB - Neutrophils play a predominant role in inflammatory and immune reactions in
inflammatory bowel disease. It is well established that the level of
myeloperoxidase, a constituent of neutrophil azurophil granules, reflects the
number of neutrophil. We examined the usefulness of determining stool levels of
myeloperoxidase in patients with inflammatory bowel disease. Myeloperoxidase
levels in stool extracts were measured using a radio-immunoassay in 33 patients
with ulcerative colitis, 32 with Crohn's disease, 9 inflammatory disease controls
and 15 normal controls. Stool levels of myeloperoxidase in active inflammatory
bowel disease patients increased significantly, and correlated with laboratory
parameters and endoscopic grade of inflammation. A paired analysis showed a
decrease in myeloperoxidase levels after the resolution of disease exacerbation.
These results suggest that stool myeloperoxidase is a simple, noninvasive, and
relevant marker of disease activity.
PMID- 9658755
TI - Impact loading on the foot and ankle and its attenuation during level walking.
AB - We studied impact loading on the foot and ankle at heel strike during level
walking. Cadaveric testing was carried out on a skin-mounted accelerometer to
estimate the bone or joint impact, and gait analysis was performed to evaluate
the impact on the foot and ankle and its attenuation during level walking.
Simulation using a rigid-body model estimated the impulse at landing during level
walking. The skin-mounted accelerometer showed the same tendency as the bone
mounted accelerometer in cadaveric testing. In the gait analysis, impact at the
calcaneus was attenuated at the medial malleolus and was less attenuated with the
ankle fixation. In the simulation, impact became greater if the foot and ankle
functions were eliminated. These results suggest that the foot and ankle are
directly involved in attenuating the impact at heel strike during level walking.
PMID- 9658756
TI - Evaluation of third generation anti-HCV test kit (SYNPEP HCV-EIA II) using sera
of inhabitants from HCV hyperendemic area.
AB - We examined the characteristics and usefulness of a third generation anti-HCV
test kit, SYNPEP HCV-EIA II (Kyokuto Pharmaceutical Inc., Tokyo, Japan). The sera
of inhabitants from a hepatitis C virus (HCV) hyperendemic area were used. The
kit had even or more anti-HCV detection sensitivity and reproducibility than
ORTHO HCV III ELISA Test System (Ortho-Clinical Diagnostic K.K., Tokyo, Japan) or
HCV PHA 2nd Generation (Dinabot Co., Ltd., Tokyo, Japan). SYNPEP HCV-EIA II
needed less total reaction time than other EIA kits, resulting in a simple
procedure. Also, HCV RNA was detected in 90% of subjects who had a 7.5 or greater
cut-off index (COI) of SYNPEP HCV-EIA II kit. In conclusion, SYNPEP HCV-EIA II
require cheap cost and simple procedure and it could be applied to mass screening
to find out HCV RNA positive persons who may need clinical care.
PMID- 9658757
TI - Usefulness of magnifying endoscopy for diagnosing tumorous lesions of the
colorectum.
AB - The usefulness of magnifying endoscopy was assessed by examining the extent to
which a magnifying endoscope can provide images of pits and by analyzing the
consistency of the pit patterns visualized by magnifying endoscopy with the pit
patterns visible under a stereomicroscope. Study materials consisted of 83 cases
of tumorous colorectal lesions. Under a magnifying endoscope, pits were visible
across the entire surface of the lesion in 46 (55.4%) of the 83 cases. The pit
pattern visualized by magnifying endoscope in 32 (69.6%) of the 46 cases was
identical to the pattern observed under a stereomicroscope. Of various pit
patterns, type IIIs (tubular, round pit that is smaller than normal pit), type
IIIL (tubular, round pit that is larger than normal pit) and type IV (dendritic,
gyrus-like type pit) were relatively well visualized under a magnifying
endoscope. It was difficult to obtain images of type V (irregular or amorphous
pit) with a magnifying endoscope. It seems therefore easy to distinguish tumors
from non-tumorous lesions using a magnifying endoscope. This imaging technique
may provide information more useful for the diagnosing tumorous colorectal
lesions and selecting therapeutic strategy, if staining methods and mucus
removing methods are improved.
PMID- 9658758
TI - Diagnosis of colorectal tumor invasion by endoscopic miniature probe
ultrasonography.
AB - We evaluated the diagnostic efficacy of high-frequency (20 MHz) ultrasound probe
(HFUP) for the staging of invasive depth of colorectal tumors. The subjects were
27 patients with colorectal tumorous lesions who were treated by endoscopic or
surgical operation (11 patients with lesions remaining in the mucosa, 13 patients
with submucosal cancer, and 3 patients with cancer invading the muscularis
propria or deeper layers). Considering the previous reports that endoscopic
mucosal resection (EMR) is indicated in cases of tumors remaining in the mucosa
or cancer slightly invading the submucosal layer, we divided the submucosal layer
vertically into three equal areas (most superficial, middle and deepest areas
which were referred to as sm1, sm2 and sm3, respectively). The depth of tumor
invasion in histological specimens was compared to the depth of tumor invasion as
assessed preoperatively using the HFUP. The HFUP-based diagnosis was identical to
the histological diagnosis in 86.4% of all cases, when the depth of tumor
invasion was rated on a three-point scale: (i) m-sm1, (ii) sm2-sm3 or (iii) mp or
deeper. These results indicate that the HFUP is very useful in selecting a
therapeutic method for colorectal tumors.
PMID- 9658759
TI - Clinical aspects of cryptogenic hepatocellular carcinoma.
AB - Clinical features of hepatocellular carcinoma in 22 patients without serum HBsAg,
HBV DNA, anti-HCV antibody and HCV RNA were characterized and possible pathogenic
factors for this cryptogenic hepatocellular carcinoma were prospectively
assessed. Twenty-two patients were selected from 434 patients with hepatocellular
carcinoma (HCC) who were treated at the Second Department of Internal Medicine,
Kurume University Hospital between January 1994 and December 1996. Serum samples
collected from these patients were all negative for HBsAg, HBV DNA, anti-HCV
antibody, and HCV RNA. Patients were evaluated based on past history, present
illness, history of habitual alcohol consumption, results of the serological and
biochemical laboratory tests at diagnosis of HCC, Anti-HBc antibody,
autoantibodies, GBV-C/HGV RNA, and histopathologic findings of non-cancerous
portion of the liver were also evaluated. Among 22 patients with non-B non-C HCC,
16 patients (72.7%) had a history of alcoholic liver disease, 6 patients had an
infection of schistosomiasis Japonica, and 1 patient had Budd-Chiari syndrome.
Nine patients (40.9%) were positive for anti-HBc antibody, but their titers were
low in all cases. Among 22 patients, positive for auto antibody, 7 patients
(31.8%) were positive for anti-nuclear antibody, and 17 patients (77.3%) were
positive for anti-smooth muscle antibody. Only 1 patient was positive for GBV
C/HGV RNA. Histopathologic examination was performed in 3 cases for non-cancerous
portions of the liver. Liver cirrhosis and liver with passive congestive fibrosis
were diagnosed in 2 cases each. The remaining one case showed normal feature of
the liver. In conclusion, the majority of the 22 patients with non-B non-C HCC
had a history of alcoholic liver disease. Many were also positive for auto
antibodies. These results suggest that patients with alcoholic liver disease or
hepatic disease with autoantibodies may be defined as the high-risk group of
developing non-B non-C HCC and should be periodically underwent a complete
medical examination.
PMID- 9658760
TI - Relationship between Lens culinaris agglutinin reactive alpha-fetoprotein and
biological features of hepatocellular carcinoma.
AB - Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), which
is a fucosylated variation of AFP, is not only sensitive and specific for
localization of hepatocellular carcinoma (HCC) but also a prognostic factor for
patients with HCC. The relationship between status of AFP-L3% in serum and
pathological findings was studied using 48 resected HCC specimens. AFP-L3
fraction was measured by lectin-affinity blotting using an AFP Differentiation
Kit L (Wako, Osaka, Japan), and was expressed as AFP-L3% (AFP-L3/total AFP x
100%). A cut-off level of 15% was used. Pathological findings of HCC such as
histological grade (well, moderately and poorly differentiated HCC), vascular
invasion, and Ki67 (MIB1), p53 (DO7) and alpha-catenin immunohistochemical
staining were studied. According to the results of serum AFP concentrations and
AFP-L3%, the 48 patients were divided into the following three groups: AFP
greater than or equal to 20 ng/ml and AFP-L3 positive (group A, n = 14), AFP
greater than or equal to 20 ng/ml and AFP-L3 negative (group B, n = 14) and AFP
less than 20 ng/ml (group C, n = 20). Ki67 labeling index of HCC tissue in group
A was 27.8 +/- 18.9%, which was significantly higher than those of group B (9.6
+/- 10.1%, p < 0.024) and group C (11.1 +/- 11.2%, p < 0.03). In group A, p53
expression was higher and alpha-catenin staining was reduced significantly
compared with those of group B or C, respectively. The results of the study
suggest that the proportion of AFP-L3% in serum reflects some biological features
of HCC.
PMID- 9658761
TI - Metastatic model of human colon cancer constructed using orthotopic implantation
in nude mice.
AB - Nude mice have been used to grow subcutis (s.c.) growing human colorectal tumors,
but these tumors rarely metastasize. This is a problem for studies into the
biological behavior of metastatic subpopulations of human colorectal cancers. We
have followed the evolution of the parental line and of a variant of human colon
carcinoma KM12 cells, that were both tumorigenic, following implantation into the
s.c. or cecal wall of nude mice. The tumors growing s.c. did not produce visceral
metastases, whereas the cecal tumors metastasized to the regional mesenteric
lymph nodes and to the liver. However, the incidence of liver metastases was
different between the parental cell line KM12C cells and the in vivo selected
cell line KM12SM cells after orthotopic inoculation. The morphological findings
of KM12 cells proliferating in a monolayered sheet revealed that these two cell
lines consisted of various cell populations. These results suggest that in the
orthotopic colon cancer models, liver metastasis is defined by difference in
subpopulations of metastatic phenotypes to the liver with early dominance of its
growth in the implanted organ. As a result, our new model using orthotopic
implantation of KM12SM cells, which produce a 50% incidence of liver metastasis,
can help to provide a technique to study the biological behavior of metastatic
subpopulations of human colon cancers.
PMID- 9658762
TI - A metastasis to the nasal tip from a cervical carcinoma--a case report.
AB - Metastases to the nasal tip from gynecological malignancies are extremely rare.
We present a case of a tumor metastatic to the nasal tip from a carcinoma of the
uterine cervix. We administered high-dose focal irradiation to the site of the
tumor. The literature on metastases to the nose, maxillary sinuses, and paranasal
sinuses from gynecologic malignancies is reviewed.
PMID- 9658763
TI - Angiodysplasia of the stomach confirmed by endoscopy and selective angiography-
report of a case.
AB - Gastric angiodysplasia that caused continuous gastrointestinal bleeding is
reported in a 75-year-old woman who had been treated with repeated blood
transfusions because of severe anemia. Endoscopic examination was performed and
revealed a bright-red lesion on the anterior wall of the upper gastric body.
Injection therapy was performed at first, but the follow-up endoscopy showed a
recurrent red lesion in same place. Selective angiography revealed a dense stain
suggestive of a hypervascular lesion, measuring about 1 cm in diameter. Partial
gastrectomy including resection of the lesion was performed. During a follow-up
period of more than 12 months, there was no sign of recurrence of bleeding.
PMID- 9658764
TI - A case of giant leiomyosarcoma of the rectum.
AB - A 63 year-old-man was admitted to our hospital with the chief complaint of
dyschezia. Digital examination revealed a large solid mass on the posterior wall
of the rectum. Endoscopically, the tumor was covered by an intact mucosal layer.
Under the diagnosis of rectal leiomyosarcoma, abdominoperineal resection of the
rectum was performed. The tumor was 10 x 9 x 8 cm in size, and its cross section
showed a gray-white tumor with central necrosis. Microscopically, the large tumor
of the rectum was mainly located in the proper muscle layer and adventitia, and
showed cellular proliferation of spindle-shaped and mild pleomorphic stromal
cells, arranged in interlacing fashion, and focal necrosis. The histologic
findings support the diagnosis of leiomyosarcoma. Leiomyosarcoma of the rectum is
a relatively uncommon disease. We report our case with reference to the
literature.
PMID- 9658765
TI - Treatment of bile leaks from cystohepatic and common hepatic duct after
laparoscopic cholecystectomy.
AB - Laparoscopic cholecystectomy is widely accepted by patients and physicians
despite the lack of controlled trials comparing this technology with conventional
cholecystectomy. The cystohepatic ducts represent accessory bile ducts of
variable size which frequently travel within the gallbladder fossa or in the
posterior wall of the gallbladder. These ducts can be injured during laparoscopic
cholecystectomy and can result in bile collection if transected. Recently, we
have experienced two cases of injury to the bile duct during operation. One case
was a transection of the accessory bile duct, the other one was an injury to the
common hepatic duct. We present herein the clinical course of the two cases, in
which biliary leakage, following laparoscopic cholecystectomy, was successfully
managed by the end to end anastomosis of the bile duct.
PMID- 9658766
TI - A case of invasive lobular carcinoma of the breast.
AB - A 43-year-old woman presented to our department with left breast lump, measuring
10 mm x 10mm x 6mm. On physical examination and mammography, the lump was
suspected to be due to mastopathy, but malignancy could not be excluded based on
ultrasonography. Excisional biopsy showed that it was an invasive lobular
carcinoma. A modified radical mastectomy was performed after obtaining informed
consent. She remained disease-free seven years after surgery.
PMID- 9658767
TI - Clinicopathological features of intraorbital neurinoma--report of two cases.
AB - Clinicopathological features of intraorbital neurinomas were investigated in two
patients. Magnetic resonance imaging (MRI) findings in Case 1 were similar to
those in Case 2. The central region of the neurinomas showed a slightly high
intensity area with a marginal low intensity on T1-weighted images (T1WI),
whereas on T2-weighted images (T2WI), the central area of the tumor was very low
intensity with a marginal high intensity area. After gadolinium-DTPA (Gd-DTPA)
injection, these areas were homogeneously enhanced in both cases. The deference
in enhancement after Gd-DTPA injection reflected the distribution of cellularity
and vessels in the tumor.
PMID- 9658768
TI - Three cases of the giant gastric leiomyosarcomas.
AB - We report three cases of giant gastric leiomyosarcoma. Diagnosis was made prior
to surgery using various diagnostic modalities. The patients were two women (77
and 77 years old) and one man (40 years old) whose chief complaints were
abdominal pain, anorexia, and tarry stool. All patients presented with a large
palpable mass in their upper abdomen at the time of admission. Based on
characteristic findings from a gastric barium study, computed tomography (CT),
and angiography, the patients were diagnosed as having gastric leiomyosarcomas
displaying extramural growth. In the first case, a patient received a total
gastrectomy, while local resection was performed in the second case because of
pedunculated extragastric development. In the third case, total gastrectomy was
combined with splenectomy and resection of the pancreatic tail. Twenty-two months
after the original operation, the first case had multiple liver metastases. We
present the three cases here, and review the literature.
PMID- 9658769
TI - A case of chronic hepatitis C with sinus bradycardia during IFN therapy.
AB - The patient was a 55-year-old male with no history of heart diseases. He was
administered recombinant IFN alpha-2b under the diagnosis of chronic hepatitis C.
Since sinus bradycardia (heart rate 40 bpm) appeared in the fourth week of
administration (cumulative dose; 240 M.U), IFN was discontinued. Bradycardia was
resolved 1 week after discontinuation of IFN, and the treatment was resumed with
a change of the regimen to IFN-beta. Since no bradycardia was noted thereafter,
IFN therapy could be completed (total dose; 108 M.U). These observations suggest
that the type of IFN or total dose contributed to the appearance of
cardiotoxicity.
PMID- 9658770
TI - A simplified method of calculating an overall goodness-of-fit test for the Cox
proportional hazards model.
AB - Gronnesby and Borgan (1996) propose an overall goodness-of-fit test for the Cox
proportional hazards model. The basis of their test is a grouping of subjects by
their estimated risk score. We show that the Gronnesby and Borgan test is
algebraically identical to one obtained from adding group indicator variables to
the model and testing the hypothesis the coefficients of the group indicator
variables are zero via the score test. Thus showing that the test can be
calculated using existing software. We demonstrate that the table of observed and
estimated expected number of events within each group of the risk score is a
useful adjunct to the test to help identify potential problems in fit.
PMID- 9658771
TI - Acute middle ear infection in small children: a Bayesian analysis using multiple
time scales.
AB - The study is based on a sample of 965 children living in Oulu region (Finland),
who were monitored for acute middle ear infections from birth to the age of two
years. We introduce a nonparametrically defined intensity model for ear
infections, which involves both fixed and time dependent covariates, such as
calendar time, current age, length of breast-feeding time until present, or
current type of day care. Unmeasured heterogeneity, which manifests itself in
frequent infections in some children and rare in others and which cannot be
explained in terms of the known covariates, is modelled by using individual
frailty parameters. A Bayesian approach is proposed to solve the inferential
problem. The numerical work is carried out by Monte Carlo integration (Metropolis
Hastings algorithm).
PMID- 9658772
TI - On tests for group variation with a small to moderate number of groups.
AB - This paper considers a family of penalized likelihood score tests for group
variation. The tests can be indexed by a measure of degrees of freedom. At one
extreme, with degrees of freedom one less than the number of groups, is the usual
score test for a fixed effects alternative using indicator variables for the
groups, while at the other extreme, in the limit as the degrees of freedom-->0,
is a test closely related to a score test based on a random effects alternative.
Asymptotic power comparisons are made for the tests in the family. As would be
expected, different members of the family are more efficient for different
alternatives. Generally the tests with smaller degrees of freedom appear to have
better power than the standard test for alternatives focusing on differences
among the larger groups, and lower power for alternatives focusing on differences
among the smaller groups. Simulations indicate the asymptotic approximation to
the distribution performs better for the tests with small degrees of freedom.
PMID- 9658773
TI - Adjusting and comparing survival curves by means of an additive risk model.
AB - Survival curves may be adjusted for covariates using Aalen's additive risk model.
Survival curves may be compared by taking the ratio of two adjusted survival
curves; the ratio is denoted the generalized relative survival rate. Adjusting
both survival curves for all but one of a common set of covariates gives the
partial relative survival rate, which measures the covariate-specific
contribution to the generalized relative survival rate. The generalized and
partial relative survival rates have interpretations similar to the traditional
relative survival rates frequently used in cancer epidemiology. In fact, the
traditional relative survival rate can be generalized to a regression context
using the additive risk model. This population-adjusted relative survival rate is
an alternative and useful method for removing confounding effects of age,
cohorts, and sex. The authors use a data set of malignant melanoma patients
diagnosed from 1965 to 1974 in Norway. The 25-year survival of 1967 individuals
is studied.
PMID- 9658774
TI - Estimating lifetime and age-conditional probabilities of developing cancer.
AB - Lifetime and age-conditional risk estimates of developing cancer provide a useful
summary to the public of the current cancer risk and how this risk compares with
earlier periods and among select subgroups of society. These reported estimates,
commonly quoted in the popular press, have the potential to promote early
detection efforts, to increase cancer awareness, and to serve as an aid in study
planning. However, they can also be easily misunderstood and frightening to the
general public. The Surveillance, Epidemiology, and End Results (SEER) Program of
the National Cancer Institute and the American Cancer Society have recently begun
including in annual reports lifetime and age-conditional risk estimates of
developing cancer. These risk estimates are based on incidence rates that reflect
new cases of the cancer in a population free of the cancer. To compute these
estimates involves a cancer prevalence adjustment that is computed cross
sectionally from current incidence and mortality data derived within a multiple
decrement life table. This paper presents a detailed description of the
methodology for deriving lifetime and age-conditional risk estimates of
developing cancer. In addition, an extension is made which, using a triple
decrement life table, adjusts for a surgical procedure that removes individuals
from the risk of developing a given cancer. Two important results which provide
insights into the basic methodology are included in the discussion. First, the
lifetime risk estimate does not depend on the cancer prevalence adjustment,
although this is not the case for age-conditional risk estimates. Second, the
lifetime risk estimate is always smaller when it is corrected for a surgical
procedure that takes people out of the risk pool to develop the cancer. The
methodology is applied to corpus and uterus NOS cancers, with a correction made
for hysterectomy prevalence. The interpretation and limitations of risk estimates
are also discussed.
PMID- 9658775
TI - A nonparametric estimator of survival functions for arbitrarily truncated and
censored data.
AB - It is well-known that the nonparametric maximum likelihood estimator (NPMLE) may
severely under-estimate the survival function with left truncated data. Based on
the Nelson estimator (for right censored data) and self-consistency we suggest a
nonparametric estimator of the survival function, the iterative Nelson estimator
(INE), for arbitrarily truncated and censored data, where only few nonparametric
estimators are available. By simulation we show that the INE does well in
overcoming the under-estimation of the survival function from the NPMLE for left
truncated and interval-censored data. An interesting application of the INE is as
a diagnostic tool for other estimators, such as the monotone MLE or parametric
MLEs. The methodology is illustrated by application to two real world problems:
the Channing House and the Massachusetts Health Care Panel Study data sets.
PMID- 9658776
TI - [An epidemic of hemorrhagic fever with renal syndrome in Croatia in 1995].
AB - In the spring of 1995, the largest outbreak of hemorrhagic fever with renal
syndrome (HFRS) so far was recorded in Croatia. There were 125 patients reported
to the National Croatian Institute of Public Health, Department of Epidemiology.
The disease occurred simultaneously in several localities, some of them close to
the previously known natural foci (Mala Kapela, western Slavonia); the focus on
Dinara was newly discovered. War circumstances in Croatia were closely related to
this outbreak. There were 50 patients hospitalized in the University Hospital of
Infectious Diseases in Zagreb; 5 of them were civilians from Zagreb area and 45
soldiers (Mala Kapela 33, Dinara 7, western Slavonia 5). In all patients the
disease was serologically proven (in 6 by indirect immunofluorescence method and
in 44 by ELISA-test). Both previously known types of viruses--Hantaan and Puumala
were diagnosed in each locality. In general, the illness was more severe in
patients with Hantaan virus infection. Two patients died, the illness was severe
in 25, moderately severe in 11 and mild in 12 patients. For the first time
inflammatory lung changes were recorded in 13 out of 37 (35.1%) patients who were
examined by X-ray in the early stage of the disease.
PMID- 9658777
TI - [War injuries of the arteries].
AB - The experience with military vascular injuries in the recent war in Crotia is
reviewed. From April 1991 to October 1995, 197 wounded persons with 231 injuries
of arteries were admitted to the University Hospital Rebro. The most common
injuries were of lower extremity arteries (54.5%), and the most frequent method
of repair was revascularisation with saphenous vein graft interposition.
Fasciotomies were performed in 34% because of frequent associated injuries of
bones (34.5%) and veins (46.7%). In 20.7% casualties pseudoaneurysms and
arteriovenous fistulas were found. Postoperative thrombosis (9%) was a
consequence of local infection, massive necrosis and sepsis. Amputation rate was
7.7%, and mortality 5.3%. These results are very satisfactory in comparison with
the results in literature. This is a result of good organization of our war
surgical service: rapid transportation of wounded persons to convenient surgical
centres and high surgical skill.
PMID- 9658778
TI - [Improvement of sanitation conditions in the liberated Croatian regions after the
"Storm" campaign--the Lika-Senj County example].
AB - More than 6,000 sq km of the central and southern areas of the Republic of
Croatia were liberated by the Storm campaign, August 4-7, 1995. On August 8,
1995, the Ministry of Health sent expert teams to the newly liberated areas, in
order to ensure the basic conditions for the displaced persons to return and live
there. To describe the public health measures taken we used the example of the
Lika-Senj County (3,746 sq km and 71,215 population). Until October 1, 1995, 50
bodies, killed in action, were detected, pathologically and forensically
examined, and then buried. Two hundred and thirty-three mostly elderly and sick
persons were admitted to the reception center in Gospic; 93 of them returned to
their homes, 133 were accommodated with their relatives and friends, and seven
were referred for treatment (four of them died). Two hundred and ten cattle
carcasses were buried using adequate sanitation measures, whereas 5,575 sheep,
3,138 head of horned cattle, 298 head of hoofed animals and 300 head of other
cattle were caught alive. The procedures of disinfection, disinfestation and
disodoration were performed in 720 apartments, 2 hotels, 3 schools, one
kindergarten, one health care unit, one sports hall and 5 shops. The main water
pump was cleared of mines and partially repaired, whereas some 20 water supply
objects were placed under surveillance. Three food depots were found and properly
treated. The entire territory was closely observed for a possible occurrence of
infectious diseases.
PMID- 9658779
TI - [Disseminated pulmonary ossification. Case report].
AB - Metaplastic pulmonary ossification is usually described as dendriform or nodular
in patients with chronic inflammatory lung disease or long-standing pulmonary
edema. We present a case of dendriform pulmonary ossification found accidentally
at autopsy in a 66-year old man. In addition, some of the theories relating to
the development of this rare phenomenon are discussed.
PMID- 9658780
TI - [Echinococcal pulmonary cyst with multiple fistulization into the bronchi].
AB - The case of a 10 year old boy with an hydatid pulmonary cyst was presented. The
cyst multiply fistulated into the bronchus. The preoperative diagnostic pathway,
the operative treatment and complete postoperative recovery was described.
PMID- 9658781
TI - [Case report of a female patient with autoimmune hemolytic anemia and cold
agglutinin antibodies].
AB - We report a case of acute transient cold agglutinin disease, the etiology of
which we could not determine with the available methods. Cold autoagglutinins had
anti I specificity, high titers of the autoantibody (> 1:1,000) and the thermal
range was relative wide. Our patient had severe haemolysis and immunosuppressive
therapy with methylprednisolone and cyclophosphamide was administered. It is a
question how much these immunosuppresive agents influenced the recovery, and in
what extent it was a self limited disease with spontaneous recovery.
PMID- 9658782
TI - [Use of intraoperative ultrasound in neurosurgery].
AB - Intraoperative ultrasound (US) is a device which is a great help to neurosurgeon
in intracerebral lesions localization, in the definition of inner tumors
structure, in its relation to the surrounding structures, as well as during
stereotaxic operations. We report our experiences with US in more than 500
operations. Its maximum usage is during gliomas and metastases operations because
of their subcortical localization. Choosing this optimal approach to the tumor,
the surrounding brain is minimally damaged. Using modern devices we are able to
distinguish edema from infiltrative gliomas, which was not possible using former
devices (both edema and gliomas are hyperechoic). In vascular neurosurgery we use
US mostly in the localization of small arteriovenous malformations (AVMs). In
pediatric neurosurgery the usage is very often in drainage operations for
ventricular catheter placement control. The main US shortage is lower image
resolution, and the basic advantage is real time imaging. It enables our prompt
intervention in every unfavorable situation.
PMID- 9658783
TI - [A model for monitoring drug prescribing in general practice].
AB - When prescribing drugs, general practitioners at the same should satisfy the
requirements of medical science and their vocation, being aware of their task of
a rational disposal of the limited resources allocated for health care. The aim
of the paper was to determine the characteristics of monitoring model for drug
prescription in general practice, taking into consideration the characteristics
of the population, morbidity, drugs and physicians. A prospective monitoring of
prescribing drug during one month was carried out in six doctor's offices of
general practice/family medicine at the Dugave-Travno Health Station of the Novi
Zagreb Health Center. In processing data on patients, drugs and physicians the
following were used: distribution description and analysis, pair's tests and
General Factorial Anova. Out of 3397 patients who visited the above mentioned
doctor's offices, 2320 (68.3%) patients were prescribed 4796 prescriptions--an
average of 2.07 prescriptions per patient (from 2.00 to 2.42). The total cost of
drug prescription was 360,117.33 kunas (from 43,632 to 77,910 kunas). The number
of prescriptions and the cost of prescribed drugs increased significantly in
terms of statistics with the age of patients (Spearman's correlation coefficient
0.2263; p < 0.001). By General Factorial Anova statistically significant
difference was determined in the cost variable among the physicians with the
impact of covariate age and number of prescriptions. Professionally, the most
appropriate and most rational prescribing was observed among physicians who had
the highest educational level and the longest experience in practice. In order to
analyze and assess the appropriatness of drug prescription in general practice,
the first essential step is to collect data on what is being prescribed, for whom
it is being prescribed, and to enable access to data for physicians. This paper
has indicated some of the characteristics of a monitoring model for drug
prescription in general practice. Formulation and implementation of this model
would considerably promote the professional appropriateness and rationality in
drug prescription in general practice.
PMID- 9658784
TI - [First page].
PMID- 9658785
TI - [The desire for information and informed consent in general anesthesia].
AB - BACKGROUND: In the last years the interest for Informed Consent (IC) in
anaesthesia has been growing and it has been debated on the adequate explanations
in order to obtain a consent. The purpose of the present study was to assess
patients' desire for information about anaesthesia. METHODS: In this prospective
study a form has been given to consecutive patients waiting for surgical
operation in general surgery or ear nose throat surgery and able to read and
write, to inform them about the necessity of General Anaesthesia (GA); they were
asked to complete a questionnaire concerning their desire for information about
the following six items concerning anaesthesia: "the duration of anaesthesia";
"what type of pain will I have when I come round, and what pain-killers will I be
given"; "details on the various types of anaesthesia, how and where will I be
anaesthetized"; "what are the most common complications of general anaesthesia";
"where and how will I come round from general anaesthesia"; "what is artificial
respiration in general anaesthesia". RESULTS: 107 patients participated in the
study, 24 of whom were undergoing surgery for malignant cancer and 83 for benign
non-oncological diseases. More than two-thirds of patients expressed their wish
to receive information, and the trend of desire to know was inversely related to
age (p < 0.05). There was no significant statistical difference in the desire to
know according either to sex or to the kind of disease (benign or malignant). The
demand for information about pain was particularly high (85%), also in the older
group of patients. The results and the difficulties for obtaining IC are debated.
CONCLUSIONS: The growth of patients' desire for information about anaesthesia is
an aspect of the evolving doctor-patient relationship in Italy. Efforts should be
directed at improving reciprocal communication.
PMID- 9658786
TI - [The effect of anesthesiologic technique on the mental state of elderly patients
submitted for orthopedic surgery of the lower limbs].
AB - Influence of anesthetic technique on mental status in elderly patients submitted
to major orthopedic procedures of lower limbs. Mental impairment is a common
occurrence in elderly patients after major orthopedic surgery. Few studies have
been published so far on this topic in spite of its relevant clinical and
economic implications. OBJECTIVE: 1) To verify whether anesthesia has a causative
role in postoperative mental confusion in elderly patients; 2) to compare the
effects of General Anesthesia (GA) and Spinal Anesthesia (SA) on mental status.
DESIGN: Controlled, comparative study. PATIENTS: Sixty patients aged > or = 70,
ASA I-II, submitted to femoral neck repair. SETTING: Anesthesia Dept. and
Orthopedic Dept. of a District Hospital in Italy. METHOD: The day before surgery
the mental status of elected patients was evaluated employing a modified Organic
Brain Syndrome (OBS) scale (Gustafsson). The better the mental status, the lesser
the OBS score. It was possible therefore to distinguish "oriented" from "confuse"
patients (38 vs 22) if they scored < or = 6 or > 6 respectively. Patients from
each group were than randomly assigned to receive either GA or selective SA.
Neither group was premedicated. GA was induced with propofol 1 mg/kg and
maintained with O2/N2O 40/60% and isoflurane; atracurium was employed to
facilitate mioresolution. Spinal anesthesia was performed with hyperbaric 1%
bupivacaine. All patients were monitored in the Recovery Room (RR) for at least
one hour. Occurrence of hypotension and/or hypoxia in the Operating Room (OR) or
the RR was immediately treated. Mental status was reassessed on the 1st and 2nd
postoperative day and results were compared with the corresponding preoperative
OBS scores both in GA patients and in SA patients. RESULTS: No statistically
significant differences were found between pre- and postoperative OBS scores in
both GA and SA group, whether "oriented" or "confuse". CONCLUSIONS: Mental status
of elderly patients submitted to femoral neck repair doesn't seem to be
influenced by the anesthetic technique chosen, independent of preoperative
psychic conditions.
PMID- 9658787
TI - [Evaluation of psychological characteristics in the preoperative phase of
patients with mental retardation].
AB - OBJECTIVES: To make easier the psychological evaluation of patients affected by
Mental Retardation and scheduled for general anesthesia. DESIGN: A form prepared
by the Psychological Service of the IRCCS "Oasi Maria SS" in collaboration with
the Service of Anesthesia was evaluated prospectively. The form is addressed to
relatives and psychologists; the interviewed person is firstly asked for a short
description of patient's personality and for any suggestion useful to patient's
management; secondly it is requested to assign a score from 1 (never present) to
5 (always present) to 44 items concerning adaptive capacities (divided into body
scheme, spoken language, receptive language, mimic-gestural language, temporal
orientation, memory), emotional and social fields (including sensibility,
dependence, and social behaviors), problematic and stereotyped behaviors.
SETTING: A medical and psychological Institute aimed at the study of Mental
Retardation. PATIENTS: Twenty-five patients affected by Mental Retardation and
scheduled for general and dental surgery. RESULTS: The form supplied a great deal
of information and suggestions for patient management. Subjects that did not
cooperative with the anesthetist presented lower scores about the ability to use
mimic-gestural language (p < 0.05) and higher scores about the presence of
anxiety or fear caused by the sight of syringes or blood (p < 0.05) and about
behaviors of flight, isolation, or aggression caused by fear (p < 0.05). By
contrast, patients presenting mild or moderate degrees of Mental Retardation
differentiated from patients with serious degree of Mental Retardation about body
scheme (p < 0.001), spoken language (p < 0.05), receptive language (p < 0.001),
temporal orientation (p < 0.001) and memory (p < 0.001). CONCLUSIONS: The form
was very useful to plan patient management. These data suggest that the lack of
cooperation by some patients affected by Mental Retardation is related to fear,
anxiety, and incapacity to communicate rather than to the degree of Mental
Retardation.
PMID- 9658788
TI - [The recurrence of hepatitic C in orthotopic liver transplantation].
AB - BACKGROUND: This study is a review of hepatitis C recurrence in patients
undergoing an orthotopic liver transplantation (OLT); to verify how many patients
HCV-positive before OLT confirm a persistent viremia after OLT and how many with
viremia show hepatitis histological evidence. METHODS: Thirty consecutive
patients, 24 males, median age 52.5 underwent OLT for posthepatitic C cirrhosis
since January 1993 in the "Transplantation Center" of Genoa. Serology included
anti-HCV search, HCV-RNA and HBV-DNA determinations, biopses were performed in
the transplanted liver within the month after operation, subsequently at every
hepatic enzymes increase. RESULTS: Twenty-one patients are currently alive,
median follow-up of 14.5 months. Before OLT anti-HCV antibodies search was
positive in all the patients while the HCV-RNA by PCR resulted positive in 17 and
negative in 4. Before OLT the HBV-DNA in patients with associated hepatitis B was
negative. After OLT 5 patients, of the 17 HCV-RNA positive before OLT, have
turned negative then all became again positive from 6 to 12 months later; 2 of
the 4 patients HCV-RNA negative before OLT have turned positive, and remained
still negative two with hepatitis C associated with hepatitis B. Although viral
replication was present in 95% of the patients, clinical and histological
evidence of recurrence was ascertained only in 29%. CONCLUSIONS: It should be
noted that the hepatitis histological picture doesn't correspond to a severe
worsening of clinical conditions, an evolution justifying transplantation. The
long-term results of this therapeutic choice are still uncertain due to the high
incidence of recurrences.
PMID- 9658789
TI - [Therapy of articular and periarticular pain with local anesthetics (neural
therapy of Huneke). Long and short term results].
AB - OBJECTIVE: Assessment of the outcomes on the articular and periarticular pain of
the knee, by a reflexotherapy with local anesthetics, denominated also
neuraltherapy. EXPERIMENTAL DESIGN: Retrospective observational study with 3
years' follow-up. ENVIRONMENT: An Ambulatory Center for Pain Management.
PATIENTS: All the patients (N = 115) with knee pain treated with neuraltherapy in
the period 1982-31 August 1996 (retired patients 2, mean age 68 +/- 15.2 years in
the remaining). INTERVENTIONS: The employed reflexotherapy, denominated also
neuraltherapy by Huneke, uses a local anesthetic (prevalently lidocaine) in 0.5
1% concentration and small quantity (0.5-1 ml for point) on tender/trigger and/or
acupuncture points, as well as in anatomical structures like articulations,
nerves, arteries or veins. The number of sessions has been of 7.03 +/- 3.3.
OUTCOME MEASURES: Outcomes are evaluated in terms of percentage subjective
improvement of the pain at the end of the therapy and at 1-3-6 months, 1-2-3
years, and then divided in 5 groups (no improvement-fair-good-very good
excellent). RESULTS: At the end of the therapy the improven cases were the 91.2%,
the 83.7% at 1 month, the 64.6% at 3 months, the 41.3% at 6 months, the 22.5% at
1 year, the 12.1% at 2 years and the 7.9% at 3 years. CONCLUSIONS: These outcomes
suggest a good effectiveness of this treatment in the painful diseases of the
knee, but further randomised double-blind trials are necessary.
PMID- 9658790
TI - [Muscular enzyme level disorders and a malignant hyperthermia susceptability
test: postoperative study of a patient with elevated CPK].
AB - The preoperative evaluation of the enzymatic level concerning the functioning of
the neuromuscular system, is of particular importance. The diseases of these
regions may lead to Malignant Hyperthermia (MH) in the course of general
anaesthesia. The authors illustrate the case of a young asymptomatic patient with
constantly high levels of CPK, who was later affected by Central Core Disease
(CCD), a rare hereditary slow progressing myopathy strictly related to MH. The
authors suggest tat preoperative CPK levels, though not predictive of a patient
to develop MH, can allow identification of patients affected by clinically silent
myopathies. This can also acquire legal importance in case of clinical MH
manifestation.
PMID- 9658791
TI - [Streptococcus pyogenes and resistance to macrolides: experience at Monza].
PMID- 9658792
TI - [Early treated congenital hypothyroidism. Evaluation of school learning].
AB - BACKGROUND: The aim of this paper was to evaluate school learning in early
treated CH children in order to investigate whether and how this pathology
influences school performance. METHODS: Using a sample of 50 early treated CH
children who have received regular follow-up at our Institute, 20 subjects
attending primary (grade) school or the final year of nursery school for
assessment of school learning have been selected. Results were compared with a
class/grade matched control group. Evaluations of cognitive, motor and language
development, T4 level determined at birth, thyroid disorder and socio-cultural
level of the family background were examined in relation to the school
performance of each child. RESULTS: The evaluations showed that out of 20 CH
children, 5 (25%) presented generalized learning disorders. This percentage is
higher than in the normal population (3.4%). When learning disorder findings were
correlated with data pertaining to motor, speech and cognitive development, socio
cultural level and thyroid disorder, it was found that children with generalized
learning difficulties presented more severe motor and speech disorders, a lower
intelligence quotient and a lower socio-cultural background than children
achieving higher scores in school tests. CONCLUSIONS: The conclusion is drawn
that early treated CH children of same age have more learning difficulties during
nursery school, while they have normal learning performances during primary
school.
PMID- 9658793
TI - [Adolescents with scoliosis: psychological and psychopathological aspects].
AB - BACKGROUND: The present study focuses on psychological and psychopathological
aspects in children and adolescents with scoliosis. METHODS: The case series
included 28 subjects with scoliosis (7 males, 21 females; range 9-25 years; mean
age 15.8 years) admitted to the Dept. of Orthopaedics of Gaslini Institute and
referred to our observation. Psychological approach included semi-structured
interviews focused on the evolution of scoliosis and based on questions about
consciousness of illness, family and patient emotional reactions during
treatment; familial, social and school adaptation; body image; onset of
psychopathological disorders. Family relational and educational attitudes were
also considered. The following psychological tests were also performed: Raven
Progressive Matrices; "Draw-a-Person" test; Sacks' battery of incomplete
sentences to evaluate cognitive aspects, body image, familial and social
relationships, interactive aspects. RESULTS: During adolescence consciousness of
illness appeared concomitantly with the beginning of treatment. Most subjects
presented intellectual-relational compensation strategies, but in a reasonable
number of cases they showed insecurity and inferiority feelings. On a conscious
level, body image appeared normal in most cases, but unconsciously (in 45% of
cases) there were anguish aspects related to feelings of body deterioration.
During long-term treatments anxious reactions, sometimes temporary, (in 36% of
cases) and depressive aspects (in 9% of cases) were observed. CONCLUSIONS: The
results obtained stress the importance of the family and the medical staff in
providing a reassuring and firm support, in order to face difficulties related to
the patient's illness.
PMID- 9658794
TI - [Descriptive analysis of measles epidemic in Palermo, from September 1996 to June
1997. Failure of a vaccination campaign].
AB - BACKGROUND: The authors report 1642 measles cases observed from September 1996 to
June 1997 at the "G. Di Cristina" Children's Hospital. 34% of patients were
hospitalized at the Division of Infectious Diseases. METHODS: The records of
children admitted with measles to emergency area were retrospectively collected.
The medical records (anamnestic, clinical and laboratory findings) of
hospitalized children were obtained from schedules which since 1993 were
performed to perspectively collect the exanthematous diseases. International
criteria for the definition of measles case were applied. The variables
considered were: background, demographic data, seasonal distribution, clinical
presentation, complications and days of hospital stay. RESULTS: The results of
this research showed that the outbreak involved predominantly infants. The
complications accounted for 72% of measles hospitalized cases. Four cases of
encephalitis were observed. A total of 1692 days of hospital stay was reported.
CONCLUSIONS: These data show the failure in measles control adopted by the
Sicilian Region and confirm the difficulties to achieve high percentage of
parents participation to the infant recommended vaccination program.
PMID- 9658795
TI - [Microcytosis. A hematological characteristic common to diverse diseases].
AB - The pathological conditions characterized by microcytosis are reviewed and their
pathophysiological mechanisms also at the molecular level are described. Moreover
clinical, haematological and laboratory findings for differential diagnosis are
discussed. Finally, the most efficacious schedules for the treatment of iron
deficiency anaemia are reported.
PMID- 9658796
TI - Human herpesvirus-7 DNA in cerebrospinal fluid.
AB - An infection by HHV-7 with presence of virus DNA in the spinal fluid was
ascertained in a twenty five month old boy with an epileptic syndrome shortly
after birth. The child was frequently admitted to hospital due to his basal
disease and frequent bacterial infections. In the occasion of one of these
hospital admissions for bacterial infections in conjunctiva, spleen and a lung,
virological investigations were also carried out disclosing the presence of HHV-7
DNA in a sample of spinal fluid and of serum and the absence of DNAs from the
other herpesviruses. The patient's monitoring for HHV-7 showed the presence of
HHV-7 DNA in a sample of serum and in various samples of peripheral blood
lymphocytes and saliva, but not in the cerebrospinal fluid sample successive to
that positive for HHV-7 DNA. Forty seven days before the diagnosis of HHV-7
infection, the patient received a human gamma-globulin therapy which obscured the
humoral response mounted against the virus by the host, so, whether the HHV-7
presence in the central nervous system was associated with a primary or a
reactivated infection remained uncertain. The absence of detectable HHV-7 serum
IgM antibody, however, suggests the HHV-7 DNA finding on the occasion of a virus
reactivation rather than a primary infection. The virological data suggest that
HHV-7 may have possibly reached the central nervous system in the course of a
viremia. The absence of HHV-6 and HHV-7 antibodies, present in the patient's
serum at a high level, support the integrity of the blood-brain barrier. A
possible pathogenetic role of HHV-7 in the child's disease seems unlikely, since
the epileptic syndrome was pre-existing.
PMID- 9658797
TI - Teenage births in the United States: state trends, 1991-96, an update.
AB - OBJECTIVES: This report provides State-specific birth rates for teenagers for
1991 and 1996 and the percent change, 1991-96. METHODS: Tabular and graphical
description of trends in teenage birth rates by age group for each State.
RESULTS: Birth rates for teenagers 15-19 years declined significantly in all but
three States between 1991 and 1996. Declines by State ranged from 6 to 29
percent.
PMID- 9658799
TI - [Detection of extracellular matrix protein (laminin) in experimental arterial
anastomoses].
AB - AIM: To investigate the distribution of Laminin in experimental microvascular
surgery. MATERIAL AND METHODS: Autografts (4 mm) of the left common carotid
artery in 20 Wistar rats were harvested after 4 weeks. The specimens were
investigated immunohistochemically for the demonstration and distribution of
Laminin. RESULTS: The demonstration and distribution pattern of Laminin was a
function of the accuracy of each single suture. In the intima, the organisation
and amount of Laminin was directed to the lumen and dependent from the distance
and vitality of the vessel segments' cells. The media had in its axis direction
the lowest reparative potency to regenerate the continuity break. The adventitia
formed a thick cuff around the anastomosis, which was circularly grown through
with Laminin-positive vasa vasorum. The marked myointimal hyperplasia in the area
around the anastomosis and in the entire autograft was constituted of Laminin
positive extracellular matrix. CONCLUSIONS: Our results support the demand for a
careful and atraumatic suture technique in microvascular surgery.
PMID- 9658800
TI - [Nager syndrome].
AB - In this publication, Nager syndrome was analyzed in the literature and six
patients from our clinic were evaluated in relation to symptoms, etiology and
pathogenesis. The diseases to be considered when making a differential diagnosis
are pointed out. Clarification of the etiology is still pending. Molecular
genetic research in these patients is possibly the key for new findings. A case
report illustrates the results of interdisciplinary treatment by the surgeon and
orthodontist. Possibilities and problems in relation to therapy are demonstrated.
PMID- 9658801
TI - [Extrafollicular variant of centrally located adenomatoid odontogenic tumor].
AB - An adenomatoid odontogenic tumor has been reported which was not connected with
any impacted or displaced tooth. The clinical and radiographical results were
consistent with a non-odontogenic cyst, but in this case the pathohistological
examination revealed string-like and partly cross-linked cells of odontogenic
epithelium as well as solid aggregates of epithelia, possessing gland-like
structures at their centers. Furthermore, small deposits of PAS-positive
materials could be seen which could be interpreted as non-mineralized dentine
with a tubular basic structure. The therapy consisted of completely enucleating
the tumor. Any recurrence of malignant degeneration has not yet been reported.
PMID- 9658802
TI - [Prospective study of the pathology of radiation-induced mucositis].
AB - One of the most severe early side effects of radiation in head and neck cancer
patients is mucositis. Inflammation of the oral mucose may lead to an extreme
subjective burden, restricting the patients' well-being and even leading to an
interruption of radiotherapy. The aim of our prospective study was to investigate
the pathological alterations of the oral mucosa during irradiation. Therefore,
samples from head and neck cancer patients were taken before radiation and a 30-G
and a 60-G radiation dose. Pathogenetic alterations were determined by
immunohistochemical staining of various cell surface molecules known to be
involved in the pathogenesis of inflammation. Staining was performed with
antibodies against ICAM 1, VCAM 1, ELAM, 25F9, 27E10, and RM3-1. Our study
demonstrates the expression rates of the various surface molecules during
inflammation. Expression of RM3-1 and ICAM 1 showed a steep increase during the
time of radiation, whereas expression of ELAM reached a low constant value.
Therefore, we conclude that distinct cell surface molecules demonstrate a
characteristic time-dependent expression during radiation. Better insight into
the pathogenesis of radiation-induced mucositis may help to develop a
pathological classification of mucositis and to improve therapeutic strategies.
PMID- 9658803
TI - [Effect of the diameter of various bore holes on retention of osteosynthesis
screws].
AB - The standard drill size for most osteosynthesis screws is about 75% of the
screw's external diameter. When screws are inserted in thick cortical bone, a
small pilot hole size can result in high torsional stress, leading to screw
fracturing. The aim of this study was to enlarge the drill size up to a critical
pilot hole size, exceeding of which leads to a rapid decrease of the screw's
holding power. Titanium screws of diameter 1.5 and 2 mm were inserted in discs of
PVC, wood and porcine mandibular bone with different thickness between 2 to 4 mm,
using pilot hole sizes of 66-95% of the screw's external diameter. The maximum
torque was recorded and pull-out tests were performed. Ten trials were conducted
for each screw-pilot hole size-material combination, yielding a total of 1560
tests. A multiphase regression analysis was performed to calculate the critical
pilot hole size (CPHS). In torque measurements, the CPHS of microscrews were
between 83% and 85% of screw outer diameter (SOD) and the CPHS of miniscrews were
between 80% and 90% of SOD. In pull-out analysis the CPHS of microscrews were
between 83% and 89% of SOD and the CPHS of miniscrews were between 79% and 91% of
SOD. The CPHS was thus found to be around 85% of the screw's external diameter.
Up to this critical point the pilot hole size may be increased without affecting
the holding power of the screws.
PMID- 9658804
TI - [Confocal laser scanning microscopy (CLSM) for validation of non-destructive
histotomography of healthy bone tissue].
AB - OBJECTIVES: Fixation (formalin), decalcification (sections) or mechanical
treatment (grinding) all bear the risk of artifacts occurring during hard-tissue
histology. Because studies on the etiology of pathological changes mostly focus
on subclinical lesions, artifacts can simulate early changes or even be
superimposed on existing changes. The objective of this study was to determine
how artifacts can be reduced. MATERIAL AND METHODS: In confocal laser scanning
microscopy (CLSM) a focused laser beam scans the surface of the specimens and
penetrates into the tissue. The intensity of the remitted light is recorded. The
confocal effect is due to an extremely small aperture (pin-hole), excluding light
from out-of-focus planes of the sample. By stepwise movement of the object table,
a tomographic series of tomographic images is obtained. Sound cortical bone
samples of the lower jaw (n = 20) were studied by light microscopy and by CLSM,
visualizing identical areas of a ground sectioned sample after H&E staining.
Additionally, embedded and fresh blocks of tissue of the same bone sample were
studied histotomographically in the CLSM. RESULTS: (1) Light microscopic
micromorphology of cortical bone can be visualized adequately in the CLSM; (2)
many structures that can be visualized by light microscopy only after special
staining (e.g., osteozyte processes) can be visualized by the CLSM using sample
blocks without pretreatment. CONCLUSION: (1) Nondestructive subsurface
histotomography by CLSM totally excludes mechanical artifacts; (2)
physicochemical artifacts can be handled more easily because fresh samples can be
studied; (3) pseudo-three-dimensional imaging allows histological interpretation
of the tissue that is equivalent to macroscopic tomographic techniques (CT, MRT).
PMID- 9658805
TI - [Experiences with distraction osteogenesis in therapy of severe peripheral airway
obstruction in infancy and early childhood].
AB - Children with craniofacial malformations are at special risk for the development
of peripheral airway obstruction. The problems are magnified in patients with
retroposition or hypoplasia of the mandible. In these cases, the base of the
tongue is posteriorly displaced, hereby decreasing the airway diameter. By
application of distraction osteogenesis the mandible can be lengthened to move
the base of the tongue forward and open the airway. Three female patients aged
between 7, 11, and 15 months suffering from peripheral airway obstruction caused
by mandibular hypoplasia were treated by gradual distraction. All of them had a
gastrostomy or a nasogastral tube in place, respectively, due to severe nutrition
problems. In the youngest patient tracheostomy was performed shortly after birth
and was already planned in the 15-month-old child, who had received a permanent
nasopharyngeal tube. The 11-month-old child suffered from severe refractory sleep
apnea. Exercises in oral feeding were possible in the youngest patient after 10
days of distraction. In the oldest one, the airway tube was removed on the six
day of distraction and, thus, tracheotomy was successfully avoided. In the 11
month-old child apneic events a rapidly decreased. Our experience suggests that
distraction osteogenesis after careful preoperative evaluation can be
successfully performed for the treatment of peripheral airway obstruction in
patients with selected craniofacial anomalies.
PMID- 9658806
TI - [Cranial and cervical chordomas. A differential diagnostic problem].
AB - Cranial and cervical chordomas can spread by para- or retropharyngeal extension
up to the region of the salivary glands or the jaw and may simulate a tumor of
the salivary glands or jaw. In occasional cases, because the tumors often expand
slowly, months or years may pass between the first clinical symptoms and
diagnosis. Diagnostic problems exist in differentiating these chordomas from
pleomorphic adenoma, mucinous carcinoma, or chondrosarcoma. Ten relevant
observations of typical cranial and cervical chordomas (Salivary Gland Register
Hamburg 1965-1996) were analyzed more closely by pathohistological and
immunohistochemical means. The exact diagnosis is based upon the evidence of
blown-up, bubble-like ("physaliform") cells which contain mucus drops in a
vacuolized cytoplasm and are surrounded by extensive areas of mucoid mucus. The
pattern of immunohistochemistry is characterized by the multifold expression of
cytokeratin, vimentin, and EMA. The differential diagnosis is discussed with
reference to further types of chordoma (chondroid chordoma, dedifferentiated
chordoma with spindle cell sarcomatous transformation), chondrosarcoma,
pleomorphic adenoma, and mucus-producing carcinoma.
PMID- 9658807
TI - [Differential giant cell epulis diagnosis--malignant melanoma of the mouth
mucosa].
AB - Malignant melanoma of the oral mucosa is a rare tumor. The clinical image can
vary, so that diagnostic errors are possible. The case of a primary malignant
melanoma camouflaging a giant cell granuloma is presented. The importance of
biopsy and histological diagnosis is underlined.
PMID- 9658808
TI - [Malignant epithelioid schwannoma of the inferior alveolar nerve.Case report with
review of the literature].
AB - Malignant epithelioid schwannoma is a very rare disease originating from the
Schwann cells. It is a subtype of malignant schwannoma. The limbs are the main
location of this entity. In our case study, the inferior alveolar nerve was
involved in the mandible. The prognosis for patients with this disease is poor,
because metastasis occurs in more than 50%. Clinical and histological features
and treatment in a 42-year-old man are discussed in detail. In addition, a short
review of the literature and treatment recommendations are given.
PMID- 9658810
TI - [Craniofacial abnormalities in the Charite Virchow Collection].
AB - On 27 June 1899 Rudolf Virchow (1821-1902) inaugurated the Museum of Pathology at
the Charite Hospital. The collection comprised 23,500 pathologic-anatomical
specimens. Most of the collection was destroyed in World War II. About 2000
samples were saved. Meanwhile the stock has increased to about 9000 objects. The
development, contents and structure of the famous Virchow Collection are
described with special reference to craniofacial deformities.
PMID- 9658811
TI - [Preoperative diagnosis of complex craniofacial syndromes].
AB - The aim of this study was to evaluate stereolithography as a tool in craniofacial
surgery. The indications were classified according to the usefulness of
stereolithography for different craniofacial pathologies. Stereolithography
models of 21 patients were built; in three cases two models were made. The age of
the 7 male and 14 female patients was 17 years on average (range: 15 months-44
years). First a helical volume CT scan of the anatomical region was performed.
After transformation of the data set, the models were built by an SLA 250
stereolithography apparatus (3D-Systems, Valencia, Calif., USA), steered by FORM
IT/DCS-Software (University of Zurich, Switzerland). The stereolithography models
were constructed by superposition of epoxy resin slices of 0.05 mm thickness,
which were polymerized by a helium-cadmium laser. These models were classified
according to the indication for stereolithography, the operation performed, the
relevance for surgical planning and the usefulness for the fabrication of
implants and protheses. In craniofacial syndromes, severe asymmetries of the
viscerocranium, large skull defects and before surgical correction of
hypertelorism these models provided important additional information for the
surgeon. Before complex interventions in these fields the construction of a
stereolithography model should be considered. In multiple fractures consolidated
in dislocation, the models proved to be less useful.
PMID- 9658812
TI - [Median craniofacial clefts. Therapy recommendations and late outcome].
AB - Median craniofacial clefts are classified as median facian cleft deformities and
are characterized by clefts of the nose involving the skull base. They can be
accompanied by hypertelorism and/or encephaloceles. From a total of 22 of our
patients with median deformities, three encephaloceles and two severe median
nasal clefts with hypertelorism were considered in 2- to-8-year-olds. Two
children with severe brain deformities died before the commencement of therapy.
The remaining median deformities were corrected as soon as possible, whereby
exclusively soft-tissue surgery was performed during the first year of life and
in no case later than school admittance. Final corrections on the nasal skeleton
were made after the age of 12. No growth disturbances of the middle face or jaw
occurred subsequent to craniotomies and corrections of hypertelorism. Plate
osteosynthesis has proven to be the most reliable method of stabilization; we
removed the osteosynthetic material in all cases. The multiplicity of possible
deformities requires that procedures be tailored to the individual case.
PMID- 9658813
TI - Possibilities and developments of intraoperative image-guided surgery in
craniofacial surgery.
AB - The standardised operational techniques of fronto-orbital osteotomy and the
various modifications used today make it possible to perform extensive surgery
for the treatment of craniofacial malformations and advanced tumours in this
region, while also allowing for a good extra- and intracranial view. Osteotomies
and resections in areas of the skull base that are normally hard to reach have
been considerably facilitated and the operational risk has been lowered. Our aim
is to achieve a further reduction of the operational risks and of the post
surgical morbidity rate through the use of techniques of computer-assisted
surgery. Especially in the area of the complex anatomy of the skull base, use of
the systems for the purpose of orientation and realisation of operational
planning as well as for the control of how radical a tumour resection needs to
be, have proved quite successful. Meanwhile, we have acquired experience in more
than 100 clinical applications of mechanical and optoelectronical navigation
systems. However, it is not possible to make changes to the presurgical data.
Also, the flexibility of the system is still somewhat limited. By introducing a
new referencing system, the flexibility and possible applications of navigation
have been increased. The current possibilities and indications for the use of
intraoperative navigation are discussed.
PMID- 9658814
TI - [Modifications of fronto-orbital osteotomy as an approach to the anterior and
middle skull base].
AB - Various extracranial, intracranial and combined extra-intracranial approaches
have been described for the surgical therapy of tumours of the anterior and
medial cranial base. A combined extra-intracranial approach is indicated in cases
in which the cranial base tumour spreads out intracranially and at the same time
into the main nasal cavity, the paranasal space and/or the orbits. These tumours
of the skull base can be surgically removed by two standardised modifications of
the fronto-orbital osteotomy--the fronto-orbito-nasal and the fronto-orbito
zygomatic osteotomy. The advantage of these surgical techniques in comparison
with other methods is that they permit a good extracranial and intracranial view
with only minimal brain trauma. Generally, additional transfacial incisions are
unnecessary. The operative techniques are described and the results of 108 cases
of tumours of the skull base shown.
PMID- 9658815
TI - [Fronto-orbital corrections and development of the frontal sinus].
AB - The development of frontal sinuses following bilateral fronto-orbital advancement
is a topic of controversial discussion in the literature. In a retrospective
study on 33 patients (15 girls and 18 boys) the development of the frontal sinus
was examined radiologically. Only patients with a minimum age of 6 years and with
at least 1 year of postoperative follow-up were included. The radiological
reference for the frontal sinus development consisted of pneumatisation at or
above the level of the supraorbital rims, as projected din postero-anterior
cephalograms. According to these criteria a frontal sinus development was seen in
72.7% of our patients. There was no statistically proven correlation between
sinus development and the sex of the patient, age at surgery or the amount of
advancement. With the exception of severe cases of Crouzon's disease we usually
expect normal development of the frontal sinus following bilateral fronto-orbital
correction.
PMID- 9658816
TI - [Clinical application of osteoinductive implants in craniofacial surgery].
AB - Autolyzed, antigen-extracted, allogeneic bone (AAA bone) is prepared from
cortical bones of human organ donors. AAA bone possesses osteoinductive
properties as it delivers BMPs from its bone matrix. Within a prospective study,
37 cranial defects were reconstructed using AAA bone implants over a period of
more than 7 years. The patients were followed-up at standardized intervals.
Roentgenographic assessments and bone scintigraphies revealed osseous integration
and remodelling of the AAA bone implants. In one quarter of the cases re-entry
was performed 10 to 18 months after the cranioplasty (removal of osteosynthesis
material, recurrence of tumor). All nine AAA bone reconstructions showed bleeding
surfaces and bony integrations. A bone biopsy was taken from the center of one of
these AAA bone implants and this showed new bone formation originating from the
surface of the implant. In one case an AAA bone implant was lost due to
infection. This is noteworthy as in approximately one third of the cases the bone
implants were in direct contact with the frontal sinus. The clinical results
clearly emphasize the therapeutical benefit of AAA bone for cranioplasties. Large
AAA bone chips from human skull bones facilitate the reconstruction of the
skull's convexity, especially when sterolithography-based operation planning is
performed.
PMID- 9658817
TI - [New hydroxylapatite cement for craniofacial surgery].
AB - A new stoechiometric mixture of 27% dicalcium-phosphate (DCPA) and 73% tetra
calcium-phosphate (TTCP) can be prepared with water intraoperatively to a paste
that subsequently sets to a structurally stabile implant composed of
hydroxyapatite (HA). Primary setting time is about 20 min; pH during setting
ranges from 6.5 to 8.5. There is no relevant curing heat or expansion or
contraction. Compressive strength is about 50 MPa, tensile strength about 8 MPa.
Over a period of about 4 h in physiological milieu, the cement converts to
hydroxyapatite. This product is no longer redissolvable in normal body fluid.
This cement can be used for non-load-bearing applications especially in
craniofacial bone surgery. Cranial defects due to tumour or trauma as well as
deficits in the facial skeleton may be reconstructed using this new biomaterial.
In nine of ten patients we used the hydroxyapatite cement successfully for
reconstructions in the craniofacial area. Fluid control of the operation field
and implant site is extremely important and sometimes difficult to achieve.
Further applications could be all non-load-bearing augmentations such as filling
of blocked paranasal sinuses, of dentoalveolar cysts and defects following dental
apectomy or fixation of implanted hearing-aid electrodes. The perspectives for
the hydroxyapatite cement include its application as a carrier for osteogenic
protein preparations, especially because of its isothermic reaction and intrinsic
osteoconductive characteristics.
PMID- 9658818
TI - [Effect of early fronto-orbital advancement on growth of the frontal sinus and
supraorbital area].
AB - In 12 patients with craniosynostosis the influence of early fronto-orbital
advancement on the growth of the frontal sinus and supraorbital region was
examined. A follow-up examination at the age of 8 years showed a lack of
pneumatisation of about 50%. However, there was no correlation between this score
and the external contour. The frontal sinus has no dominant influence on the
growth of the supraorbital region. In 9 out 12 of cases the very early operation
time did not lead to disturbances of growth. A further follow-up examination of
the patients after termination of growth at the age of 16 is planned.
PMID- 9658819
TI - [Long-term outcome after corrective surgery of the neuro- and viscerocranium of
patients with simple and syndrome-related premature craniosynostosis].
AB - A retrospective and partly prospective study was conducted to analyse both
clinically and cephalometrically the craniofacial growth pattern of patients with
isolated and syndrome-related premature craniosynostosis after standardized
fronto-orbital and midface advancement. The file data of 293 children with fronto
orbital advancement were evaluated over an average period of 4.4 years. In
addition, lateral teleradiographies of 117 patients from this group were
cephalometrically analysed. Moreover, late results of 36 children and 8 adults
with midface-advancement with an average follow-up period of 4.5 years were
assessed. In contrast to linear craniectomy and so-called lateral canthal
advancement, in only 8.2% of cases (24 out of 293 patients) were relapses
requiring reoperation found in this study after fronto-orbital advancement. The
evaluations indicate that with simple forms of craniosynostosis such as
trigonocephaly and plagiocephaly predominantly very good or good growth can be
observed. Cephalometric evaluation confirmed the limited potential of growth in
the area of the anterior skull base and in the midface in the presence of
syndrome-related faciocraniosynostoses. In such cases the cephalometrically
confirmed maxillary hypoplasia, which increases in severity in the following
order of syndromes 'Saethre-Chotzen-Crouzon-Apert-Pfeiffer', could be influenced
only to a limited degree by fronto-orbital advancement. For this reason midface
advancement is of secondary importance in children with very severe anomalies. In
the present evaluation, a high rate of relapse of midfacial hypoplasia was to be
found in children and adolescents after this operation in accordance with other
references. Therefore, the indication for Le Fort III osteotomy in the growth
period should be limited.
PMID- 9658820
TI - [Cranial development after corrective skull surgery in craniosynostosis].
AB - Craniofacial development may be potentially implicated after vault corrections in
cases of craniosynostosis. The aim of this prospective study was the
investigation of the surgical effect on calvaria growth, correlating the
percentiles of a group of patients before and after craniosynostosis correction
in relation to the normal percentiles of growth. The patient population consisted
of 71 children; the postoperative follow-up time in 57 patients was more than 12
months. Of the children followed up, 36 were male and 21 female. Thirty-six cases
involved untreated non-syndromic craniosynostosis; the remaining 21 were syndrome
cases. The patient ages ranged from 16 to 27 months. In 11 cases correction of an
occipital craniosynostosis was carried out. The fronto-occipital circumference
was registered in accordance with Prader's percentile table. The operative method
included a fronto-parietal craniotomy, the temporary removal and shaping of the
fronto-orbital band and a vault cranioplasty. During follow-up 13 patients
treated with fronto-orbital advancement in cases of isolated craniosynostosis
remained in the registered percentile curve. In 13 patients a change to a lower
percentile curve was confirmed; 1 patient changed to a higher curve. In cases of
syndromic craniosynostosis 10 patients remained in the post-operatively
registered percentile curve; 8 patients changed to a lower and 1 patient to a
higher percentile curve. No growth restriction of the reshaped calvaria after
surgical correction of craniosynostosis was observed. No significant difference
was found in the potential calvaria growth between syndromic and isolated
craniosynostosis.
PMID- 9658821
TI - [Midfacial callus distraction in a patient with Crouzon syndrome].
AB - The treatment of syndromic hypoplasias of the midfacial complex, for example in
Crouzon patients, is necessary at an early stage for functional and aesthetic
reasons. If midfacial advancement is done by the traditional technique using bone
grafts, it has often been seen that the normal occlusion originally achieved
changes in an Angle class III, because the mandible grows regularly but not the
midface. This problem could probably be solved if midfacial advancement is done
by the gradual callus-distraction procedure. The local osteogenesis involves the
possibility that there is normal growth of the midfacial complex even if the
operation is performed in young children. Based on experience in mandibular bone
lengthening, this new method was used in a 10-year-old Crouzon patient. As
successful lengthening of the midface needs a stable device and a reliable base,
a new midfacial distractor was designed using the principle of the halo-frame.
With an advancement of about 22 mm the midfacial position was normalized and a
regular overbite was achieved. In a case report the new technique is shown and
the results are demonstrated and discussed. Despite this encouraging early result
a long-term follow-up is not yet possible.
PMID- 9658822
TI - [Interdisciplinary surgical therapy of tumors of the frontal skull base].
AB - Most tumors of the anterior cranial base invade both the intra- and extracranial
regions at the borderline of the cranial and facial skeleton. In surgical
treatment of these lesions, combined craniofacial approaches are applied in
accordance with the anatomical conditions. Surgery is performed by an
interdisciplinary team of neurosurgeons and maxillofacial surgeons. To evaluate
the effectiveness and the complications of this surgical concept, the data of 58
patients treated over a 10-year period were collected. In these patients, 60
operations were performed, including two operations for tumor recurrence. In 38
cases, complete tumor removal was achieved. One patient died in the early
postoperative period because of pulmonary embolism. Significant neurological
deficits occurred in three patients. In most cases, postoperative complications
and functional disability were both due to intradural invasion of the tumor.
Nevertheless, in the majority of the cases radical tumor removal is achieved with
acceptable morbidity when microsurgical techniques are applied for the resection
of the intradural tumor. Both the meticulous repair of dural defects and the
reconstruction of the anterior cranial base and orbit contribute distinctly to a
reduction in the rate of postoperative complications and to acceptable cosmetic
results.
PMID- 9658823
TI - [Craniofacial techniques in traumatology].
AB - The coronal incision is a versatile approach to midface or skull base fractures.
It allows the open reduction of complex fracture sites and facilitates
canthopexy, marginotomy or calvarian bone harvesting. By this method, primary
treatment can be optimised and the rate of secondary corrective surgery can be
reduced. All trauma patients who underwent this kind of intervention were re
examined to check functional and aesthetic results. The complication rate was low
and the advantages of these techniques are evident, so that it is suggested that
the indication for this operative approach should be extended.
PMID- 9658824
TI - [Obliteration of the frontal sinus with lyophilized cartilage in frontal
fractures].
AB - Obliteration of the frontal sinus is frequently necessary in the appropriate
treatment of major craniofacial trauma of the upper third of the face. Successful
frontal sinus obliteration requires (1) meticulous removal of the frontal sinus
mucosa, (2) permanent occlusion of the nasofrontal duct and (3) obliteration of
the denuded cavity. The current techniques include implantation of autologous
fat, bone or muscle. These techniques are effective when the appropriate
guidelines are respected, but the problems of donor site morbidity, which has
been as high as 5%, recipient site morbidity due to the shrinkage of the free
graft, and the increase in the operative time must be pointed out. The unique
characteristics of lyophilized cartilage, i.e. the low resorption rate and
tendency to undergo osseous substitution, justify its use for obliteration of the
frontal sinus. The present study reviews 51 patients with obliteration of the
frontal sinus due to craniofacial trauma. In none of the patients were there
clinical or radiological signs of postoperative mucocele formation. Progressive
ossification of the implanted cartilage was verified in most of the patient
population.
PMID- 9658825
TI - [Reconstruction of the frontobasal skull after tumor operations and trauma.
Transplant selection and functional outcome].
AB - Defects of the frontoorbital complex subsequent to extensive tumor surgery or
severe trauma often result in aesthetic and functional disharmonies. The long
term results of rehabilitation related to different materials and techniques are
the subject of this study. From 1974 to 1996 altogether 127 patients with bony
defects of the orbit and/or the skull base underwent surgery. All patients' data
were documented prospectively from 1984 onwards. The results following
reconstruction with autologous calvarian transplants in 52 patients were compared
to those of a control group which received iliac bone or PMMA implants. Eighty
one bony defects (64%) resulted from tumor resection; 37 patients (29%) suffered
from the effects of trauma. In 67 cases (53%) reconstruction was performed
primarily, in 51 cases (40%) secondarily. Free or pedicled soft-tissue
transplants were necessary in order to separate the orbit and the neurocranium in
26% of the defects. On the other hand, small, isolated defects of the orbital
roof (7%) were left without any reconstructive procedure. Contrary to the iliac
bone grafts, the calvarian transplants resisted secondary resorption.
Postoperative infections appeared in two cases; loss of transplants was avoided
entirely in the group of calvarian reconstructions in contrast to the alloplasts.
The selection of a suitable donor site area and rigid fixation with microplates
led to excellent esthetic results even in cases with large defects.
PMID- 9658826
TI - [Standardized occipital advancement. A new method for therapy of lambda suture
synostosis].
AB - Lambdoid synostosis can manifest unilaterally, bilaterally or in combination with
other craniosynostoses. Using the concept of fronto-orbital advancement we
developed occipital advancement in order to correct unilateral or bilateral
lambdoid synostosis. The process involves striped transversal osteotomy, removal,
remodelling and advancement of the occipital region. It allows precise,
reproducible and predictable positioning of the segments. Artificial sutures are
created as a result of the osteotomy. The remodelling leads to a well
proportioned skull shape and advancement to an increase in the intracranial
volume. This article presents the operative method and the results of 14
patients.
PMID- 9658827
TI - [Occipital correction in scapho- and plagiocephaly].
AB - The operation technique and the results after occipital correction in children
with plagiocephaly and scaphocephaly are reported. The indication for the
intervention is provided by aesthetic and functional considerations. The outcome
is very good; the growth of the skull follows the same range of percentiles as
preoperatively and normal mental development is seen.
PMID- 9658828
TI - [Treatment of non-synostotic, pediatric skull deformities with dynamic head
orthosis].
AB - In all craniofacial deformities the differential diagnosis between synostotic and
non-synostotic conditions must be made. While the first group is usually subject
to intracranial surgical intervention, the treatment of non-synostotic
deformities is the subject of controversial discussion. Often associated with
premature birth, restrictive intrauterine environment or torticollis, these
conditions; also defined as positional deformations, can lead to severe
plagiocephalic head shapes. Dynamic orthotic cranioplasty is a conservative
method of treating these deformities in early childhood by means of an
individually fabricated orthotic head band. The principle is that dynamic
pressure is applied to prominent parts while leaving space for growth in
depressed areas. In accordance with this principle, various deformities can be
addressed. Through clinical, anthropometric and radiographic evaluation it has
been shown that dynamic orthotic cranioplasty can correct positional deformation
of the cranial vault, skull base and upper face with no relapse following
treatment. It must be emphasised that the method is simple, easy to handle and
very effective when treatment starts within the first 6 months of life.
Therefore, its potential should be recognised by paediatricians and craniofacial
surgeons.
PMID- 9658829
TI - [Tumor reduction of plexiform neurofibroma in the craniofacial and neck area].
AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease of
high penetrance and variable expression. Epidemiologic data on craniofacial
manifestations are still lacking. Up until now 74 patients with NF1 have been
treated at the Department of Oral and Maxillofacial Surgery of the University of
Hamburg. Forty-two patients presented periorbital and orbital neurofibromas
varying in extension and in the severity of findings of the affected site.
Surgical therapy is mainly based on tumour reduction, frequently combined with
face-lifting. In our experience neurofibromas of the neck tend to be pseudo
encapsulated, facilitating the preparation of the tumour. On the other hand,
identification and preparation of diffuse infiltrating neurofibromas in the
trigeminal nerve region are difficult and local recurrence must be expected.
PMID- 9658830
TI - [MRI 3D imaging of the orbits in craniofacial abnormalities and injuries].
AB - Craniofacial malformations and trauma often lead to changes in orbital soft
tissues that require operative correction of both hard and soft tissues. CT scan
and 3D reconstructions are optimal tools for the evaluation of the bony
structures but there is no equivalent for the orbital soft tissues. The aim of
this study was to establish a 3D-MRI technique that allows differentiated
visualization of the different soft-tissue types of the orbit. A total of eight
patients with different pathologic conditions of the orbit were examined. Five of
these patients came for secondary correction after trauma and three showed a
craniofacial malformation. 3D reconstruction was performed in volume-rendering
technique after acquisition of 3 mm axial slices. It was shown that
differentiated visualization of the orbital soft tissues is possible. Even though
the thin bony structures have a weak signal and therefore the imaging is poor,
the globe could be reconstructed reliably by different radiologists because of
its circular delimitation from the bone. This technique provides additional
support in the planning of orbital operations.
PMID- 9658831
TI - [Results of surgical therapy of orbital abnormalities].
AB - Dystopies of the bony orbit are caused mainly by craniosynostosis, facial clefts
and encephaloceles. This article presents the results of the surgical correction
of orbital hypertelorism in 24 patients. Using this operation technique, the bony
interorbital distance was decreased from an average of 47.6 mm to 22.8 mm.
However, the distance between the soft tissues was not reduced by the same amount
as the distance between the bony orbits. The intercanthal distance decreased from
an average of 58.5 mm to 44.5 mm, whereby an additional refixation of the medial
palpebral ligament resulted in a reduction of the intercanthal distance to 40.8
mm. A strabismus divergens was seen preoperatively in 18 patients,
postoperatively only in 8 patients. Four of the latter had to undergo operative
correction of the diplopia. We conclude that the operative technique is not
reserved only for complex cases of hypertelorism because it shows satisfactory
functional and aesthetic results with a low complication rate.
PMID- 9658832
TI - [Using individually designed ceramic implants for secondary reconstruction of the
bony orbit].
AB - The use of autogenous transplants and the application of intraoperatively
customised alloplastic materials show, in cases of secondary orbital
reconstruction, a higher postoperative morbidity caused by additional approaches
to the transplant donor site. On the other hand, thorough surgical exploration
and fitting of the transplants or alloplastic materials greatly prolongs
operating times. For these reason we designed ceramic implants (Bioverit) on the
basis of stereolithography models and prefabricated them using a commercially
available dental copy milling unit (Celay). In five cases up until now seven
customised implants have been inserted for reconstruction of the lamina
papyracea, zygomatic complex and infraorbital floor and rim. Encouraged by the
good postoperative aesthetic and functional results, with significantly reduced
operating times and morbidity in all cases, we will continue to take this
technique into account for reconstruction after complex orbital fractures.
PMID- 9658833
TI - [Orbital decompression in treatment of endocrine orbitopathy].
AB - Graves' ophthalmopathy (Graves' disease) is a grave, rare immunological
inflammatory reaction of the postorbital connective, adipose and ocular muscle
tissue. Graves' disease occurs only within the scope of immunothyropathies and
constitutes the most frequently encountered extrathyroidal manifestation. Typical
symptoms are a result of the volume increase of the postbulbar connective and
adipose tissue and of the interstitial swelling of the ocular muscles.
Clinically, we find a spectrum of increasingly grave changes in the orbita, such
as infiltration of the eyelid and connective tissue, exophthalmos, swelling of
the muscles, damage to the cornea and involvement of the optic nerve with loss of
vision. Regarding functional impairment of the optic nerve (optic nerve
compression), orbita decompression represents an operative ultima ratio. Between
January 1992 and April 1997, 11 patients (22 orbitae) from a group of more than
600 patients with Graves' disease with vision involvement were treated
surgically. All treatment data were documented prospectively. Surgical
intervention was performed only in cases where a progressive loss of vision
existed in spite of retrobulbar irradiation and high-dose glucocorticoid therapy.
Surgical therapy consisted of decompression of the medial, inferior and lateral
orbital wall and of the orbital contents via combined bi-coronary and anterior
access. The long-term results demonstrated improved vision conditions with 17 of
the 22 eyes operated on. Parameters such as vision, exophthalmos, VEP, motility,
double vision and field of vision were documented pre- and post-operatively. The
prediction of post-operative deviations of the bulb axis was limited, and these
were rectified through secondary displacements of the ocular muscle. No
complications worth mentioning were encountered. In extreme events of therapy
resistant Graves' ophthalmopathies with progressive loss of vision, the three
wall decompression method has proved to be the correct one.
PMID- 9658834
TI - [Interdisciplinary diagnosis and therapy of traumatic optic nerve damage].
AB - Traumatic optic nerve lesions (TONL) still pose a large clinical problem
concerning early detection and treatment. Neuro-ophthalmology provides reliable
tests to detect afferent lesions but these methods are limited to just 30% of the
severely injured patients. Especially in the patient with multiple injuries,
optic nerve injuries are hardly predictable. In the latter group we established
well-known neurophysiological methods for early detection of afferent disorders
of the visual pathway, i.e. flash-VEP ERG. Apart from these diagnostic problems
of TONL, controversy still surrounds the appropriate treatment of TONL--whether
conservative or surgical or even combined treatment should be advocated. Our aim
was to establish a reliable diagnostic schedule, based on the combination of
neuro-ophthalmological, spiral-CT and clinical findings, and a treatment plan, so
that in any patient there is a distinct guideline as to whether there is a need
for early treatment of the peripheral visual pathway or not. In 52 patients who
were assessed by the above-mentioned schedule, we could detect any of the 20
afferent disorders of the peripheral visual pathway. Although it is difficult to
prove therapeutic effects on the injured optic nerve, immediate combined
conservative treatment plus optic nerve decompression helped in three patients,
who reported unilaterally no light-perception at admission, to regain at least
partial recovery of afferent function of the visual pathway. Most of the trauma
units still handle the problem of optic nerve trauma with a 'wait and see'
policy. This is not regarded as an up-to-date option, since there are
alternatives, and these will be outlined.
PMID- 9658835
TI - [Foreign body removal in orbits and frontal cranial base].
AB - Owing to their rare incidence, foreign body injuries in the region of the orbit,
skull base and skull have up to now mostly been treated in the literature by
means of case reports. Here we present our experience and treatment regimen for
ten patients we have treated during the last 3 years. In seven cases the foreign
body was located in the orbit alone, whereas in three others the orbit and the
frontal base were equally involved. Except for one case, the foreign material
could be removed completely. Three patients suffered from partial or complete
loss of vision and one patient developed a psychosyndrome during the follow-up
period, but no late effects were registered in the remaining six cases. Before
removing the foreign body and carefully reconstructing the accident, however, we
strongly recommend the documentation of possible functional deficits, preferably
by means of photography. CT is the method of choice for localising the foreign
body, except for the depiction of wood particles. Here, sonography and MR should
be performed. As the therapeutic approach, the cooperation of an
interdisciplinary team of ophthalmogists, neuro- and maxillofacial surgeons seems
mandatory. To avoid inflammation, the immediate removal of the foreign material
is recommended in cases with considerable intracranial lesions: post-operative
neurologic and intensive care monitoring should be provided. Treatment is
completed by high-dose antibiotics, using CSF-soluble substances and, if
necessary, anti-convulsives.
PMID- 9658836
TI - [Experimental reconstruction of the sheep orbit with biodegradable implants].
AB - In a complex animal model in sheep, polydioxanone (PDS) and polylactic membranes
were used for the reconstruction of large orbital-wall defects. In a long-term
experiment over 1 year, polylactic implants alone showed the best performance as
compared with combinations involving autogenous bone grafts and titanium
miniplate fixation. As soon as these polylactic implants are approved for human
surgery, they will be used to solve the still challenging problem of anatomical
reconstruction of large comminuted fractures of more than one orbital wall.
PMID- 9658837
TI - [New techniques in maxillofacial surgery: local injection treatment with
botulinum toxin A].
AB - Intramuscular injections of botulinum neurotoxin type A cause reversible
chemodenervation and subsequent paralysis by blocking the presynaptic release of
acetylcholine. Botulinum toxin type A has emerged as the most effective form of
symptomatic treatment for abnormabilities in muscle movement (blepharospasm,
hemifacial spasm, torticollis) and has been approved for use in these conditions.
First results in the treatment of patients suffering from oromandibular dystonia,
myogenic craniomandibular dysfunction and recurrent dislocation of the
temporomandibular joint are presented. In most cases, therapeutic effects
occurred within 1-6 days post-injection. Muscular hyperfunction was reliably
reduced and involuntary activity patterns gradually ceased. No severe side
effects of the local injections were noted.
PMID- 9658838
TI - [Botulinum toxin treatment of neurogenic dislocation of the temporomandibular
joint].
AB - Botulinum toxin leads to paresis of the skeletal muscle lasting 2-4 months via an
inhibition of acetylcholine release at the neuromuscular junction. Since 1995,
botulinum toxin injections have been used in the treatment of recurrent
dislocation of the temporomandibular joint (TMJ). The chemical denervation of the
external pterygoid muscle restricts the angle of mouth opening, thus helping to
prevent dislocation. TMJ dislocations that occur as a result of increased tone in
the protracted masticatory muscles were recently defined as neurogenic
dislocations of the TMJ. We conducted a clinical study to investigate the
efficacy of botulinum toxin injections into the external pterygoid muscle in five
patients with recurrent neurogenic dislocations of the TMJ. In the 3 months prior
to the first treatment, the patients had suffered a total of 19 dislocations. In
the 3-month period following the initial treatment, only one woman experienced a
dislocation. We performed the treatment a total of 25 times. Five dislocations
occurred during the 6- to 36-month observation period. In the meantime, two
patients remain recurrence-free 1 year after receiving treatment. All the
patients had a restricted ability to open their mouths as a side effect of the
weakening of the external pterygoid muscle that was completely reversible over
the course of 3-4 months. All other side effects were equally well-tolerated by
the patients and fully reversible after 3 weeks at the most. In the two patients
who remain recurrence-free without any further treatment, the increased tone of
the muscles serving the jaw normalised spontaneously over the course of the
underlying neurological disease. Our results show that, in the treatment of
recurrent neurogenic dislocations of the TMJ, botulinum toxin injections
represent a therapeutic alternative that has few side effects.
PMID- 9658840
TI - [A new device for reproducible computerized tomography in improved diagnosis of
surgical maxillofacial conditions].
AB - The aim of this study was the evaluation of a newly developed radiotranslucent
headholder (craniostat) in order to improve diagnosis of maxillofacial pathology.
In this prospective study, 103 patients with maxillofacial pathology were
examined preoperatively with a Philips SR 7000 computed tomograph using this
craniostat. The apparatus was applied fixing the patient's head at three points
(meatus acusticus externus on both sides and the glabella). The control group
consisted of 106 patients with similar pathology who were examined by computed
tomography without a headholder. The application of the craniostat resulted in
the following advantageous findings: (1) reproducible CT scans, therefore very
precise assessment of the course of a disease; (2) fewer motion artifacts; and
(3) symmetrical posture of the patient's head. This headholder is helpful in
improving maxillofacial diagnosis by computed tomography if a symmetrical,
reproducible posture of the patient's head is to be achieved and motion artifacts
could otherwise make the interpretation of the resulting images much more
difficult.
PMID- 9658839
TI - [3-D imaging of the facial surface by topometry using projected white light
strips].
AB - Three-dimensional registration of the facial surface by methods which are
currently in use is difficult because of the long measuring times required by
point-based imaging systems. Artifacts caused by movement appear, e.g., blinking.
Also the production of a facial plaster-cast model for measuring is not an
adequate solution. In order to acquire data of the facial surface in a contact
free manner, a system is needed that has short measuring times, is able to record
data of complex surfaces and at the same time does no harm to the open eyes. The
method described here represents a new development of an industrial high tech
CAD/CAM system. Unlike customary point-based imaging systems, the stripe
projection method works using entire planes. Structured light is aimed at the
surface to be measured, recorded by videocamera and calculated by triangulation;
then the different views are combined by computer. The system has an optic sensor
that can record approximately 500,000 measuring points within seconds (ca. 1.7s).
Test persons' faces and plaster-cast models of them (n = 15) were measured
comparatively and serially (n = 5) to test the validity and reliability of the
method for maxillofacial procedures. These investigations show that this method
is appropriate for recording three-dimensional soft-tissue profiles. First
studies on patients before and after dysgnathia operations were undertaken. A
prospective long-term study for collecting data on pre- and postoperative
dysgnathia patients has been begun. Initially, it will record the changes in
facial soft tissue on the basis of skeletal displacement. Later, predictions
about the soft-tissue changes subsequent to dysgnathia surgery can be worked out
on the basis of stored data matched with three-dimensional bone data.
PMID- 9658841
TI - [Results of measurement of pre- and postoperative milling models of orthodontic
surgical treatment of dysgnathia patients].
AB - PURPOSE: Three-dimensional realisation of CT by models produced by a milling
machine and stereolithography has become a useful procedure for the diagnosis of
craniomaxillofacial disharmonies. We used three-dimensional milling models to
verify the results of operations involving sagittal splitting of the mandible.
MATERIAL AND METHODS: Fifteen models from patients with mandibular prognathism
and 31 models from patients with mandibular retrognathism, made preoperatively
and 6 weeks postoperatively, were examined for three-dimensional changes of the
osseous anatomical structures. RESULTS: The mandibular corpus had been shifted
between 1 and 3 mm forward in the group of patients with mandibular retrognathism
and by the same distance backward in the first group. In the group with ventral
shifting, the intercondylar distance increased by 2.9 mm, while it decreased by
1.9 mm in patients with the mandibular backshift operation. Furthermore, the
distance between the muscular processes increased by 6.6 mm in the first group
and decreased by 1.6 mm in the second. The Bonewill angle decreased by 1.6
degrees in patients after ventral shifting and increased by 1.7 degrees in the
dorsally shifted group. Contrary changes in the left and right gonion angle were
seen: if the right decreased, the left increased. The same situation was found in
both groups. CONCLUSION: We noted remarkable changes in the condylar position and
anatomy after sagittal splitting of the mandible.
PMID- 9658842
TI - [Intraoperative precision of mechanical, electromagnetic, infrared and laser
guided navigation systems in computer-assisted surgery].
AB - Intraoperative precision in computer-assisted surgery depends on the
characteristics of a navigation system, the precision of correlation between
object and data set, the position, number and fixation of landmarks, and the
parameters of the data set. The characteristics of a navigation system, in
particular the immanent precision, can be detected by the use of the geometric
model and navigation analyzer developed at the University of Regensburg with the
support of Carl Zeiss, Germany. The precision of five navigation systems of
different types and technology was measured: Viewing Wand (ISG, mechanical
system), the SMN microscope (Carl Zeiss, infrared system with laser autofocus),
the MKM system (Carl Zeiss, robot platform with laser autofocus) and the STP
pointer (Leibinger, infrared system). The immanent precision of these systems
ranges from 0.1 to 2.0 mm. An electromagnetic system (3-Space Digitizer,
Polhemus) was compared; this produces serious spherical deviations of 10.0 to
20.0 mm in the presence of metal, surgical and rotating instruments, and
circuits. The application of these different systems for craniomaxillofacial
surgery is discussed.
PMID- 9658843
TI - [Biological activity of E. coli expressed BMP-4].
AB - BMP-4 is physiologically present in low concentrations in human bone matrix. So
far the protein has only been produced in small quantities by expression in
mammalian cell cultures. In this study we investigated the biological activity of
E. coli-expressed BMP-4. In vitro neonatal rat muscle tissue was incubated
together with BMP-4 during 4 h, followed by an incubation period of 14 days on
cellulose acetate membranes in BMP-free medium. The addition of 0.4 microgram BMP
4 induced cartilage formation in 1/8 samples while 4 micrograms BMP-4 showed
chondroneogenesis in 2/10 samples. When the BMP-4 concentration was increased to
40 micrograms, new cartilage formation was seen in 5/7 samples. In vivo BMP-4 was
implanted intramuscularly for 3 weeks in ICR mice. Amounts of 10 micrograms rhBMP
4 and more (up to 100 micrograms) constantly induced heterotopic ossicle
formation. BMP-4 was also combined with a collagen carrier and implanted for 2
and 4 weeks in the abdominal muscle of SD rats. While 0.4 microgram BMP-4 showed
no bone or cartilage formation, the amount of 40 micrograms BMP-4 showed new
heterotopic cartilage formation, followed by endochondral ossification in almost
all samples. The results prove that E. coli-expressed BMP-4 possesses the same
inductive properties as mammalian-cell-expressed BMP-4.
PMID- 9658844
TI - Preoperative assessment of airway patency in the planning of corrective cleft
nose surgery.
AB - OBJECTIVE: To investigate acoustic assessment of complex structural anomalies in
cleft lip and palate associated nasal deformities and its impact on the planning
of corrective rhinosurgery. PATIENTS: Twenty-three consecutive patients with
unilateral CL(P) during routine consultations, three of them prior to corrective
surgery. INTERVENTION: Acoustic measurements of the nasal airway crosssectional
area were obtained for both nasal cavities. The size of isthmus area and isthmus
location as well as the nasal volume and decongestion capacity in various regions
of interest were determined. RESULTS: Obstructions in the area of the nasal valve
(< 0.4 cm2) were detected in 85% of the patients on the cleft side, but only 15%
on the contralateral side. Severe mucosal hypertrophy was a common finding on the
cleft side with a significantly higher capacity of decongestion, especially in
the posterior region of the nasal cavity (P < 0.02). A second stenosis located
behind the physiological isthmus was found in 16 patients. CONCLUSION: Acoustic
rhinometry is a noninvasive, objective method. It measures the degree and the
exact location of airway obstructions. Apart from the equipment, the only
prerequisite is a cooperative patient. The measurement has direct therapeutic
consequences. If the exact cause and location of airway stenosis are known, it is
easier to adapt the corrective surgical procedures to suit the individual
patient. The decision in favour of additional therapeutic measures can be made on
a more rational basis to prevent residual airway problems postoperatively.
Preoperative acoustic rhinometry offers valuable information concerning the
severity and location of nasal airway obstructions and thus proves to be a
helpful tool in the planning of corrective operative measures.
PMID- 9658845
TI - Objective evaluation of velopharyngeal function by acoustic reflection
measurements.
AB - OBJECTIVE: To investigate whether acoustic pharyngometry is capable of
discriminating velopharyngeal mobility in cleft and non-cleft subjects by
determination of epipharyngeal volume changes with active muscle function.
DESIGN: Case control study, consecutive sample. SETTING: Cleft palate
rehabilitation centre. PATIENTS: Thirty-three consecutive cleft palate patients,
among them 10 following pharyngeal flap surgery and 32 controls without
velopharyngeal pathology. INTERVENTION: Transnasal acoustic measurements of
airway cross-sectional area in the state of relaxed and tensed pharyngeal
muscles. Determination of epipharyngeal volume changes by integrating the
difference of the airway profile from the choane for a distance of 5 cm (EV0-5).
Measurements of defined changes in the epipharynx served as reference. RESULTS:
Acoustic pharyngometry is capable of discriminating (P < 0.05: U test, Mann
Whitney) the volume effect of velopharyngeal mobility in CP patients (6.5 cm3)
from the control group (8.0 cm3). A 'pharyngeal flap type' and a 'non-pharyngeal
flap type' of restriction was observed. The individual effect of
velopharyngoplasty on pharyngeal mobility can thus be determined. CONCLUSION:
Acoustic pharyngometry is a non-invasive, quantitative investigation technique
which seems well suited for the evaluation of velopharyngeal mobility. We expect
it to be a helpful tool in objectively monitoring the effect of therapeutic
intervention on velopharyngeal mobility, and it may provide a better
understanding of the pattern of movement in CP patients.
PMID- 9658846
TI - New perspectives in head and neck sonography by signal-enhanced color Doppler
sonography.
AB - Ultrasound contrast agent is used in color Doppler flow imaging for signal
enhancement in perfused vessels. We present our experience with its use in the
head and neck area and the results obtained. Up until now, 30 patients with
carcinomas of the oral cavity or the maxillary sinus, tumors of the mandible and
metastatic or inflammatory lymph nodes have been examined. Conventional B-scan
sonography was supplemented by non-contrast color Doppler flow imaging. Depending
on the indication, 2.5 g Levovist in bolus or 4 g fractionated was injected
intravenously in a concentration of 300 or 400 mg/ml. The administration of the
contrast agent was tolerated by all patients without any side effects and in all
cases led to a remarkable enhancement of the Doppler signals. About 15 to 30 s
after injection, an enhancement in perfused vessels was detected. The fractioned
injection of 4 g led to a lengthening of signal enhancement up to more than 10
min and to the possibility of examining more parts with a single application of
contrast agent. In 64% of the lymph nodes, vessels could only be identified with
the administration of Levovist. The general vessel topography could be better
evaluated in 83% of the cases. The lymph-node-supplying vessels were identified
in 8 of 11 patients after the injection of contrast media. Additional
information, which was gained in 17 patients, increased the certainty of
diagnosis or of the therapeutic concept. In three cases, the examinations with
the signal enhancer resulted in a change in therapy. By applying signal enhancer
in color Doppler sonography the fields of examination in the head and neck areas
can be expanded.
PMID- 9658847
TI - [Endoscope-assisted fixation of condylar fractures of the mandible].
AB - The reduction and plate osteosynthesis of condylar fractures often require a wide
extraoral approach with the risk of facial nerve palsy. The endoscopic technique
is an alternative. Seven condylar fractures were operated on under endoscopic
control. In three patients a newly developed device for endoscopically controlled
plate application was clinically tested for osteosynthesis. In two cases fracture
healing was achieved. In the third case the plate had to be removed early due to
insufficient screw fixation. The new device and the application technique are
described in detail. This technique may be helpful in further minimizing trauma
surgery.
PMID- 9658848
TI - [Status of the temporomandibular joint after orthodontic-surgical interventions
with and without concomitant orthodontic treatment].
AB - PURPOSE: This study was conducted to control improvement in the high preoperative
prevalence of TMJ symptoms in patients treated by long-term orthodontic therapy
for class II malocclusion. PATIENTS AND METHODS: A total of 57 patients were
examined at least 8 years after surgery, 37 having received orthodontic treatment
and orthognathic surgery and 20 surgery but without orthodontic treatment.
Myofunctional, disk and condylar symptoms were recorded according to the Krough
Poulsen scheme. RESULTS: Both groups showed a normal maximal interincisal
distance. The deviation during the opening movement was mainly sigmoidal in the
group with orthodontic treatment and terminal in the other group. Muscular pain
predominated in the group without orthodontic treatment. Clicking sounds of the
TMJ were registered in 70% of both groups. Occlusal interference and a higher
interocclusal distance when speaking were found more often in patients without
orthodontic treatment. Preoperatively, clicking and crepitation sounds had been
recorded in 60% of both patients groups. CONCLUSION: In conclusion, a high
postoperative prevalence of TMJ dysfunction symptoms was found in patients with
class II malocclusion 8-10 years after orthognathic surgery with or without
orthodontic treatment. Both groups often exhibited TMJ clicking and crepitation
sounds, whereas the patients that had not received orthodontic treatment had a
higher prevalence of occlusal interference and muscular pain.
PMID- 9658849
TI - [Function and morphology of the temporomandibular joint after mandibular
translocation osteotomies with and without positioning plates].
AB - Positioning devices are commonly used to avoid the malpositioning of the proximal
segments in bilateral, sagittal split osteotomies and to make sure the
preoperative fossa condyle relation is reproduced. The aim of our prospective
study, with random selection of 24 patients, was to compare the morphological and
functional outcome of the TMJs. The proximal segments in half of the patients had
been positioned using devices, in the other half without devices. The segments
were fixed by transoral bicortical miniscrew fixation. The evaluation of function
is based on pre- and postoperative clinical and electronic axiographic
investigations. To study the TMJ morphology, we performed MRI and X-ray
investigations preoperatively and 6 months postoperatively. Preoperatively, 12
patients showed slight dysfunction, six patients moderate, and six patients
severe dysfunction. Postoperatively, no patient was symptomless. Slight
dysfunction was presented in 15 cases, moderate dysfunction in five and severe
dysfunction in four cases. Evaluating the axiographic investigations
preoperatively, 22 patients showed no mobility disturbances of the TMJ. Two
patients showed severe mobility disturbances. Postoperatively, a significant
increase in TMJ mobility disturbances could be seen. The MRI investigations of
both groups showed both worsening and improvement in the disk positions. No
significant differences could be determined between the two groups, however.
Regarding the X-ray investigation, three patients from the group with positioning
devices showed dislocated condyles; in the group without positioning devices four
cases of condyle dislocation were seen. All dislocations were transversal except
for one case in the group without positioning devices. Positioning devices do not
seem to improve the functional and morphological outcome of the TMJ after BSSO.
PMID- 9658850
TI - The changing face of mental health managed care.
PMID- 9658851
TI - The managed care context: emerging practices.
PMID- 9658852
TI - Behavioral health: a view from the industry.
PMID- 9658853
TI - Utilization review and the treatment of mental illness: emerging norms and
variabilities.
PMID- 9658854
TI - The economics of behavioral health carve-outs.
PMID- 9658855
TI - Medicaid managed care for special need populations: behavioral health as "tracer
condition".
PMID- 9658856
TI - Quality assurance in behavioral health.
PMID- 9658857
TI - Consumer and family views of managed care.
PMID- 9658858
TI - Behavioral health contracting.
PMID- 9658859
TI - The effect of the Utah Prepaid Mental Health Plan on structure, process, and
outcomes of care.
AB - Capitation reduced Medicaid costs but had limited effects on most measures of
process and outcome. Clients under capitation with the poorest mental health at
baseline performed more poorly over time on some measures.
PMID- 9658860
TI - Managed mental health experience in Colorado.
PMID- 9658861
TI - Managed mental health experience in Massachusetts.
PMID- 9658862
TI - The future of behavioral health.
PMID- 9658863
TI - [Molecular genetics of gliomas].
AB - Gliomas represent the majority of primary central nervous system tumors in
adults. The moderate overall impact of conventional therapeutic regimens on these
inherently aggressive neoplasms raises the need for a direct intervention in the
biology of neoplastic change. In the last decade important achievements in the
molecular genetic basis of deregulated cell-cycle have been brought about, the
neuro-oncologic implications of which are reviewed here. Loss of equilibrium
between promoting factors and negative control of mitosis emergeus as a general
principle, with gene amplification-overexpression operating in the former group,
while deletions, loss of function-type mutations and post-transcriptional events
prevail at the opposite pole. Damage to regulatory mechanisms will result, as a
major consequence, in transgression of one or more of the so-called restriction
points of the cell-cycle. Lesions of the genome are further ramified by
supracellular processes involving autocrine and paracrine growth-stimulating
loops. Malignant progression of gliomas, therefore, can be envisaged as a
cumulative sequence of genetic alterations and interactions of tumor cells with
their microenvironment.
PMID- 9658864
TI - [Hemorheologic parameters in coronary artery disease].
AB - Hemorheological parameters were proved to be primary risk factors in ischemic
heart disease (IHD) by several studies. In the present study the relation of
these parameters to the severity of coronary artery disease (CAD) was examined.
The data of 109 patients (mean age: 55 +/- 9 yrs) undergoing coronary angiography
and 59 healthy controls (mean age: 35 +/- 10 yrs) were analyzed. Hemorheological
parameters [hematocrit, fibrinogen level, plasma viscosity (PV) and whole blood
viscosity (WBV)] were measured and circulatory index (CRI) was calculated.
Patients were classified into three groups according to their coronary vessel
state based on the coronary angiogram: Group 1 (n = 19, mean age: 53 +/- 8 yrs)
without significant CAD, Group 2 (n = 19, mean age: 51 +/- 11 yrs) with single
vessel disease, Group 3 (n = 71, mean age: 57 +/- 8 yrs) with multivessel
disease. All the measured hemorheological parameters of IHD patients were
significantly higher than those of controls. Fibrinogen and PV was significantly
elevated in Group 2 and 3 comparing to Group 1 (p < 0.05 and 0.01). Hematocrit
and WBV was significantly increased in Group 3 comparing to Group 1 and 2 (p <
0.05). CRI was significantly decreased in IHD patients, and it was also lower in
Group 3 than in Group 2 (p < 0.05). These results indicate that hemorheological
parameters may play a role in the pathogenesis and development of CAD.
PMID- 9658865
TI - [HIV protease inhibitors (new possibilities in the treatment of HIV infection and
AIDS)].
AB - In HIV/AIDS illness the reverse transcriptase and protease enzymes of human
immunodeficiency virus (HIV) are currently the agents of antiretroviral therapy.
Nucleoside analogues were the first group of drugs which exerted antiviral
activity in humans. More recently protease inhibitors have provided new
approaches in the treatment of HIV-infection and AIDS. Impressive clinical
results have been obtained with combined therapies of three antiretroviral drugs,
including one protease inhibitor. It is worth to mention that apart from the
above, many new compounds are under development, including the vaccine against
HIV.
PMID- 9658866
TI - [Clinical experience with enzymes (collagenase, protease) in the treatment of
skin lesions caused by CO2-laser surgery].
AB - The authors applied collagenase and protease in lipofil solution for the
treatment of skin lesions caused by CO2 laser interventions. 354 surgical
interventions were performed on 91 patients (43 verruca vulgaris, 32 naevus
intradermalis, 16 keratosis). The laser methods were excision or/and vaporisation
of the lesion. The authors created methodological groups and all of the patients
had a control laser wounds without enzymatic treatment. The patients were
controlled periodically from the 1st to the 56th postoperative day. The first
experience shows that, the use of enzymatic treatment is advantageous for the
laser wounds healing. The colour, scar formation and other aspects proved to be
better after the enzymatic treatment. The optimal method was the use of the cream
for 2-4 postoperative days on very thin layer, without bandage. The result seemed
to be better compared with the enzymatically untreated cases.
PMID- 9658867
TI - [Biometry: data scales].
AB - In this paper the author shows the basic concepts of the different data scales,
which are important from statistical investigations points of view. He summarizes
the characteristics of each scale and presents their sample data.
PMID- 9658868
TI - [In memory of the 175th anniversary of the birth of Ignac Hirschler].
PMID- 9658869
TI - [Nomination of Jozsef Torok in Debrecen].
PMID- 9658870
TI - [Bacterial vaginosis].
AB - Bacterial vaginosis being the most frequent vaginal infection is the leading
cause of genital fluor. The author reviews the latest developments regarding the
etiology, diagnostics and therapy of disease. Per os metronidazol and
intravaginal clindamycin play the main role in treatment. The most often
occurring complications of bacterial vaginosis are premature rupture of membrane
and premature labour, postpartum endometritis, pelvic inflammatory disease and
gynecological postoperative infections.
PMID- 9658871
TI - [The effect of theophylline preparations on morphine-induced spasm of Oddi's
sphincter in man].
AB - In this paper a short overview is given about pathophysiology of Oddi's sphincter
function and diagnosis as well as pharmacological therapy of the hypertonic
dyskinesia. According to the pharmacological background of muscle relaxation in
other organs, theophyllin preparations: aminophyllin and retard theophyllin were
used to inhibit spasm of Oddi's sphincter provoked by morphine in 9 patients with
hypertonic dyskinesia of biliary and/or pancreatic outlet. The enzyme elevations
(SGOT and/or amylase) and pain response to morphine significantly diminished in
all but one patient during the evocative tests and the effect seemed to be dose
dependent until about 500 mg of theophyllin. The long acting theophyllin may be
useful in hypertonic Oddi's sphincter dyskinesia mainly in combination with
nitrates to prevent nitrate tolerance and intolerance and for treatment of
"idiopathic" pancreatitis as well as "postcholecystectomy" syndrome. It might
prevent papillary stenosis and adenomyosis which seem to be precancerous states
of the papillary tumors.
PMID- 9658872
TI - [Anesthesia for heart transplantation].
AB - Heart transplantation, as a therapeutic possibility, has been available since
1992 in Hungary. The authors present the anaesthetic aspects and clinical
experiences of this worldwide used therapeutic method. The specialties of the
narcosis, the importance of the aseptic techniques, and the treatment of the
denervated heart are emphasised.
PMID- 9658873
TI - [Computer tomography and interventional radiologic methods in the diagnosis of
acute pancreatitis].
AB - The authors supervised the case record of 51 patients admitted between 1994
January and 1996 March suffering from acute pancreatitis. Diagnosis was made upon
clinical signs, laboratory findings, abdominal ultrasound and CT examinations. In
total 121 CT examinations were made mostly by using contrast material. Patients
were classified with the help of Balthazar's grade. The authors emphasize that CT
currently is the most accurate single imaging modality for diagnosis, staging the
severity of the inflammatory process, and detecting complications of acute
pancreatitis. They suggest that the first CT examination should be done within 3
days from the onset of the illness. In cases falling under group "C", "D" or "E"
of Balthazar's grade, the CT examination should at least be repeated within 10
days. With 6 patients in septic state the bacteriological findings gained by fine
needle aspiration was of great value for the further treatment.
PMID- 9658874
TI - [Quinidine-induced syncope simulating transient cerebral ischemic attack].
AB - A case of quinidine-induced syncope with prevailing neurological symptoms is
reported in which the transient right-sided hemiparesis and fluctuating soporific
state was induced by recurrent torsades de pointes ventricular tachycardias. In
connection with this case, attention is paid to the difficulties of differential
diagnosis and to the consideration of cardiac and metabolic disorders mimicking
TIA or ischaemic stroke.
PMID- 9658875
TI - [Treatment of mycobacterial lung diseases in patients without HIV infection].
PMID- 9658876
TI - [Evaluation of diagnostic and therapeutic management in patients with
bacteriologically negative pulmonary tuberculosis].
AB - The study aimed at assessing the frequency and type of errors in the diagnosis
and management of newly registered bacteriologically negative cases of pulmonary
tuberculosis. Random sample of 560 out of 7272 such patients registered in 1993
was subject of detailed analysis of all available medical documentation. The
analysis was performed by an independent team of three specialists:
pulmonologist, radiologist and epidemiologist. The results of the analysis
indicate insufficient utilization of modern available diagnostic methods. Apart
from clinical assessment the main basis for diagnosis of tuberculosis was A-P
radiography. Tomography examination was performed in 35.5% of patient only,
bronchoscopic in 19.8% and cytologic examination of sputum in 15.9%.
Bacteriological examinations during the first phase of diagnosis, usually in
hospitals, were satisfactory. Error in diagnosis was found in 63 patients, i.e.
11.3% of cases. The treatment in patients considered as correctly diagnosed, was
in the intensive phase correct, but in the continuation phase--too long.
PMID- 9658877
TI - [Analysis of diagnostic errors and recommendations of diagnostic procedures in
bacteriologically negative pulmonary tuberculosis].
AB - The paper presents a detailed analysis of errors in the diagnosis of
bacteriologically negative pulmonary tuberculosis in a random sample of 560
patients out of all such patients registered in 1993. The false diagnosis was
found in 63 patients i.e. in 11.3% of the sample. Among the 63 patients with
false diagnosis of tuberculosis there were 15 cases with lung cancer, 15 cases
with pneumonia and/or pleuritis, 15 cases with disease of circulatory system with
abnormal radiological of the lungs, 8 cases with old post-tuberculosis changes in
the lung considered as relapses, 4 cases of bronchiolitis obliterans with
organizing pneumonia, 3 cases of sarcoidosis and 1 case of aspergillosis in a
post-tb cavity. The most serious errors were those related to failure in
diagnosing (or of too late diagnosis) of lung cancer. These failures comprised
2.7% of patients in the sample. The chance to detect a lung cancer in the sample
was 2900 cases in 100,000 men and 2200 cases in 100,000 women. This chance was
much higher than in general population--29x for men and 100x for women. The main
source of errors was false interpretation of radiological examinations and
neglect to utilise other diagnostic procedures like bronchoscopy, cytology or
tomography examinations. As an outcome of the analysis authors present their
recommendations for diagnostic procedures in the diagnosis of bacteriologically
negative pulmonary tuberculosis.
PMID- 9658878
TI - [A new, automatic, non-radiometric system for culturing MB/BACT bacilli and its
value in the microbiologic diagnosis of tuberculosis].
AB - The MB/BacT is a fully automated, rapid, non-radiometric system, for the culture
of Mycobacteria for clinical samples other than blood. CO2 production is measured
and reported as reflective units from the MB/BacT Process Bottle colorimetric
sensor. We are evaluating the MB/BacT system in comparison to our routine culture
method--culture on egg media (glycerol and puruvate), in the Bactec 460-Tb
radiometric machine and in MB Redox. A total of 286 clinical samples from
respiratory tract were inoculated into three or four culture systems and
incubated at 37 degrees C. There was only little difference in mean time to
detection between the MB/BacT and Bactec system (for M.tuberculosis 11 days
versus 9 days), but both systems were faster than egg media (16 days).
Contamination rates for MB/BacT system was 8.4%, and for Bactec 6.9%. The
colorimetric technology used in the MB/BacT is a rapid and sensitive for the
measurement of mycobacterial growth.
PMID- 9658879
TI - [Use of Polymerase chain reaction (PCR) for detection of Mycobacterium
tuberculosis complex from patient materials].
AB - The polymerase chain reaction (PCR) and direct culture were applied for detection
of Mycobacterium tuberculosis complex in samples obtained from patients with
suspicion of pulmonary and extra-pulmonary tuberculosis. In the reaction of
amplification IS6110 was applied as a target region, and PCR reaction products
were of the size of 123 bp and 317 bp. A total of 278 samples (158 sputum, 36
urine, 25 pleural effusion, 23 bronchial washings, 8 blood, 4 stomach washings, 3
cerebrospinal fluid, 2 fragments of skin, 2 pleural effusion, and 17 others
samples) from 181 patients were tested. Mycobacterium tuberculosis complex was
detected by PCR in 144 out of 278 samples and by culture in 68 of 278 samples.
The PCR test enabled a rapid and sensitive diagnosis particularly in a number of
samples which were negative on culture.
PMID- 9658880
TI - [Usefulness of redux properties in acid-resistant bacilli for rapid detection of
their growth in culture].
AB - MB REDOX a new system for detection of Mycobacterium is described. It is a
modified, serum supplemented Kirchner-medium containing a colourless tetrazolium
salt reduced by the redox system used for self-indicating microbial growth. In
this study we have tested sensitivity and time of isolation of Mycobacteria in MB
REDOX and compared to the other different systems of cultivation.
PMID- 9658881
TI - [The influence of rifampicin on selected parameters of immunologic response].
AB - Rifampicin (RMP), antituberculous drug, has been controversially described for
many years as an immunosuppressant. The goal of this work was to determine the
influence of RMP on selected parameters of the immune response in vivo and in
vitro. In vivo (in B6AF1 mice) the influence of long-term treatment on primary
humoral response and cellular response was evaluated. Drug dose was 50 mg/kg. In
vitro (using peripheral blood of volunteers) the influence of RMP on mitogen
induced proliferation, metabolic activity of granulocytes and leukocyte induced
angiogenesis by diverse subpopulation of mononuclear cells was examined. The
concentrations tested were 7 and 70 micrograms/ml. RMP slightly stimulated
production of anti-SRBC antibodies and suppressed cellular response in mice,
decreased PHA and ConA induced proliferation in higher concentration and strongly
inhibited chemiluminescence at concentration used. RMP inhibited also leukocytes
induced angiogenesis.
PMID- 9658882
TI - [Changes in the respiratory system of patients with rheumatoid arthritis-
personal observations].
AB - 13 patients with RA admitted to our Institute with symptoms of respiratory
involvement were described. Taking under consideration pulmonary function tests,
radiological findings and histological examinations, we recognised 7 cases with
interstitial lung disease, 3 cases with recurrent respiratory infection with
bronchiectasis, 1 case with pleuritis, 1 with Caplan's syndrome and 1 with
alveolar haemorrhage. The role of RF, and treatment with gold in the development
of interstitial lung disease, as well as character of physiologic abnormalities
concerning the small airways and its potential connection with bronchiolitis were
discussed.
PMID- 9658883
TI - [Coexistence of obstructive lung diseases and lung cancer].
AB - Connection between histological type of lung cancer and existence of clinical and
spirometric symptoms of COPD was analysed in 110 lung cancer patients (64 small
cell, 23 adenocarcinoma, and 23 squamous). It was shown that adenocarcinoma was
significantly more frequent among subjects with values of FEV1%VC over 70 than
among subjects with small cell and squamous lung cancer. Also subjects with
values of FEV1% VC over 70 had significantly higher oxygen blood pressure, and
clinical and radiological symptoms of COPD were less intensive than in subjects
with values of this index below 70. There was no correlation between histological
type of lung cancer and bronchoscopic symptoms of bronchitis and radiological
symptoms of emphysema.
PMID- 9658884
TI - [Cytostatic treatment of patients with advanced non-small cell lung cancer].
AB - 92 patients with advanced non-small cell lung cancer were treated with cisplatin
80 mg/m2 day 1 and etoposide 120 mg/m2 on days 1-3. In 58 of them vinblastine 5
mg/m2 was also applied on days 1 and 3. In 25% of all cases partial response and
in another 26% minimal regression was found after 2 courses of chemotherapy,
independently to treatment modality. Partial regression was observed
significantly more often in patients with adenocarcinoma, but survival time was
significantly shorter in this group. Median survival time was 8 months for all
patients, 10 months for stage IIIB and 6 months for stage IV. This difference was
significant.
PMID- 9658885
TI - [Analysis of patients registered in outpatient departments for tuberculosis and
lung diseases in group VI N (neoplastic) during the first half of 1995].
AB - 2115 cases of chest neoplasms were registered during the first six months of 1995
in Pulmonary Outpatient Departments in Poland. In 865 (40.8%) patients squamous
cell cancer was diagnosed, in 344 (16.2%)--small cell lung cancer, in 174 (8.2%)-
adenocarcinoma, in 107 (5%) other types of lung cancer and in 5.6% of cases--lung
cancer with undefined histology. Predominated subjects aged from 60 to 69 years
(43.5%). Lung cancer under 50 years of age was observed significantly more often
among women (25.8%) than among men (13.5%). Moreover adenocarcinoma was much more
frequent among women than men and significantly more cases of lung cancer were
recorded in nonsmoking women. Diagnosis was established during the first 4 weeks
in 38.9% of patients but 23.6% of patients have waited for it more than 39 weeks.
Surgical treatment was advised in 16.9% of subjects, radiotherapy in 14.3% and
26.4% of patients underwent chemotherapy. Treatment analysis was presented
according histological type of lung cancer. Occupation, performance status,
clinical stage of the disease, prevalence of cancer in patients families were
also analysed.
PMID- 9658886
TI - [Transthoracic needle biopsy under USG control].
AB - In 114 patients with peripheral lung lesions transthoracic needle biopsy was
performed under USG control. This method enabled to achieve positive results in
more than 90% of cases. Transthoracic needle biopsy is a simple diagnostic method
which allows without serious complications to establish histo-pathological
diagnosis of thoracic peripheral tumors.
PMID- 9658887
TI - [A case of binocular blindness in small cell lung cancer].
AB - A was reported case of binocular blindness associated with small cell lung
cancer. Most probably this complication was a clinical manifestation of the
paraneoplastic syndrome. No tumor response was induced with chemotherapy and
patient died due to tumor progression.
PMID- 9658888
TI - [Congenital esophago-tracheal fistula in an adult].
AB - A 33 year old man with recurrent respiratory tract infections was admitted to
surgery ward. During esophagoscopy and bronchoscopy--esophago-tracheal fistula
was found. Diagnosis was confirmed by radiologic examination of esophagus.
Surgical treatment was performed with good result.
PMID- 9658889
TI - [A case of lipoid pneumonia].
AB - The 58 years old woman with chronic cough, dyspnea and infiltrations in low area
of left lung was described. Antibiotics were not effective. Cancer cells were not
found during bronchoscopy. Explorative thoracotomy was made. Lipoid pneumonia was
recognised. Just now the patient has completed history: she has taken lipoid
nasal drops for many years.
PMID- 9658890
TI - [Oncogenes and suppressor genes in lung cancer].
PMID- 9658891
TI - [Pulmonary complications of chronic liver diseases].
PMID- 9658892
TI - [Pulmonary changes in the course of rheumatoid arthritis].
PMID- 9658893
TI - [Exogenous surfactant preparations].
PMID- 9658894
TI - [Current trends in prevention and therapy of postmenopausal osteoporosis].
PMID- 9658895
TI - [Adverse drug reactions in childhood. A drug surveillance study in Sicily].
AB - The aim of the present study was to investigate the spontaneous reports of
suspected adverse drug reactions, observed in paediatric patients in Sicily
during the period between the 1st January 1995 and the 31st August 1997. The ADRs
were classified according to the "WHO Programme for International Monitoring of
Adverse Reactions to Drugs". On 1020 reports, the paediatric suspected ADRs were
130 (12.7%); 23% of these was serious, and 29.2% involved children aged 3 years
or less. The antimicrobial and the musculoskeletal drugs were responsible of
74.6% of the whole suspected paediatric ADRs. Cutaneous and gastrointestinal
apparatus were involved in 70% of reports and were the most frequently targets of
ADRs. On 57 different molecules ceftriaxone and co-amoxiclav were the most common
drugs causing ADRs with a percentage of 13%. In 45.4% of ADRs the suspension of
the treatment occurred, in 34.6% therapy was needed besides the suspension of the
drug, whilst in 11.5% patients needed an hospital visit. In 59.2% spontaneous
reports were sent by hospitals, in 32.3% by primary health care and the remaining
percentage by other sources. Our investigation should stimulate physicians to
better evaluate the potential side effects of drugs and the cost/effectiveness
profile of paediatric therapies.
PMID- 9658896
TI - [Transient immunosuppression after abdominal surgical intervention].
AB - Transient immunodepression appears a few hours after surgery and usually
regresses spontaneously within 15-20 days. In this study, cellular and humoral
immunity parameter values were compared prior to and 24 h, 7 days and 14 days
after laparotomic and laparoscopic cholecystectomy (12 patients and 25 patients
respectively) operated at the University of Turin's First Surgical Clinic, to
look for differences in the immunological effects of these two types of surgery.
The following parameters were determined: IgG, IgA, IgM, C3, C4, granulocytes
(CD11c), lymphocytes, B lymphocytes (CD19, CD19-CD15), T lymphocytes (CD3), T
helper cells (CD3-CD4), T suppressor cells (CD3-CD8), CD4/CD8 ratio, NK cells
(CD16), monocytes (CD14, CD11c-CD14), IL-2 receptor expression (CD25), HLA-DR
expression (total HLA-DR, HLA-CD3), total cytotoxic activity (CD57), T cell
cytotoxic activity (CD8-CD57), and NK cell cytotoxic activity (CD16-CD57).
Granulocytes increased significantly (p < 0.05) in both groups. The increase was
more marked in the laparotomy group and still evident on the 7th and 14th days.
Total T cells, T helpers and NK cells fell after 24 h (p < 0.05) in this group
only. These results suggest that laparoscopy is associated with less substantial
immunological changes than laparotomy.
PMID- 9658897
TI - [An unusual site of bleeding from esophageal varices].
AB - A case of massive upper gastrointestinal haemorrhage from proximal esophageal
varices is reported. Upper esophageal varices occur rarely, and serve as
collaterals in conditions of superior vena cava obstruction. In our patient,
cervical esophageal varices were associated with portal hypertension due to
occult liver cirrhosis. As the diagnosis was made at autopsy, this case serves to
stress the importance of a through examination of the cervical portion of the
esophagus during routine endoscopy.
PMID- 9658898
TI - Recurrent Salmonella sepsis and aortitis in a patient with hepatocellular
carcinoma.
AB - A 62 years old man was admitted to hospital because of fever; a small superficial
hepatic nodule was showed by ultrasonography. Blood cultures grew Salmonella
enteritidis. Cefotaxime was administered for ten days. Fever promptly disappeared
but one week later recurred with abdominal and back pain. Cultures grew again
Salmonella enteritidis. Biopsy of the hepatic nodule showed hepatocarcinoma.
Computed abdominal tomography showed a paraaortic mass. Angiography demonstrated
hematoma communicating with the aortic lumen. The patient underwent
revascularization of the involved aortic tract and resection of the hepatic
nodule. Histology showed suppurative aortic endarteritis and a well
differentiated hepatocellular carcinoma with a large area of suppurative
necrosis. The recovery of Salmonella species as of any uncommon bacteria from
blood should warrant a through research of underlying disease, especially cancer.
PMID- 9658899
TI - [Patient-gastroenterologist relations: a viewpoint].
PMID- 9658900
TI - [Esophageal dislocation by aberrant right subclavian artery].
PMID- 9658901
TI - [Role of abdominal echography in internal medicine].
PMID- 9658902
TI - [Obsessive-compulsive disorders: clinical forms and comorbidity].
PMID- 9658903
TI - [Dyspepsia: a reappraisal problem].
AB - Dyspepsia is a major public problem. It occurs in 25-40% of the general
population negatively affecting the quality of life. 2-3% of the patients visited
by the GP and up to 30% of those visited by the gastroenterologist have
dyspepsia. Both diagnostic procedure and therapy are expensive. Definition,
aetiology and pathogenesis of the disorder are not clear cut. The aim of this
review is to outline the main trends in the relevant area of the clinical
practice. The authors choose the most comprehensive definition among the thirty
of the medical literature. To rule out, the most commonly and frequently wrong
opinions risk factors have been examined. The authors distinguished between
symptoms of function and organic dyspepsia and those of Irritable Bowel Syndrome
and Gastro-Esophageal Reflux Disease, which often overlap and make difficult the
management of the patient. The aetiology and pathogenesis have also been
discussed, with particular emphasis on Hp. Advantages and drawbacks of different
diagnostic approaches have been investigated. An age and symptoms related
approach of the cases with dyspepsia is proposed, which allows to manage the
patient without the necessity of invasive procedures. It is finally suggested
that are cases which can be managed by the GP and others for whom the
gastroenterologist intervention is mandatory.
PMID- 9658904
TI - [Evidence-based medicine. 3. Systematic reviews: a tool for clinical practice,
permanent education and health policy decisions. Italian Group on Evidence-Based
Medicine-GIMBE].
AB - The reviews of research, summarizing a great amount of studies in a manageable
format, are invaluable tools for physicians, inundated with enormous amount of
biomedical information. However, narrative reviews are often misleading because,
mixing together opinions of authors and results of research, the relation between
clinical recommendation and evidence is partial and based on a biased citation of
primary studies. In contrast to narrative reviews, the systematic reviews
assemble, critically appraise, and synthesize the results of primary studies
addressing a specific topic. Additionally their authors use strategies for
minimizing bias and random error. The science of systematic reviews is now
supported by the Cochrane Collaboration, an international network established for
"preparing, maintaining and disseminating systematic reviews of the effects of
health care". The authors provide tools for searching, critically appraising and
using in practice the systematic reviews, which use can help physicians to
improve the transfer of research in clinical practice, a task obliged by
limitation of financial resources to physicians of any health service.
PMID- 9658905
TI - [Approval of clinical trials].
PMID- 9658906
TI - [Adult respiratory distress syndrome and nitric oxide].
PMID- 9658907
TI - [Difficulties in the approval of clinical trials in Spain. An obstacle race].
AB - Time required until approval of clinical trial protocols as well as the more
common bureaucratic problems were studied. A questionnaire was administered to
AMIFE members and our experience was analyzed regarding twenty-two multicenter
clinical trials performed from 1993 to 1996. Payment to centers resulting in
indirect costs ranged from 10% and 30% relative to the total cost of the study in
the center and median time to obtain the trial approval was 112 days. Some
possible solutions to improve the efficiency in the process of protocol approval
are noted.
PMID- 9658908
TI - [Acute respiratory distress syndrome: incidence and course in a Spanish ICU].
AB - We have analyzed the 57 ARDS admitted at the Intensive Care Unit (ICU) of the
Hospital General Vall d'Hebron of Barcelona in 1996 (the 5.7% of the ICU and the
0.18% of the hospital admission). We have studied the epidemiological
characteristics, as well as their ICU complications and mortality. This year was
the first to have nitric oxide (NO) as complementary treatment in the ARDS
patients at our hospital. They were 42 males and 15 females, with a mean age of
60 years, APACHE II 21 and a lung injury score 3.1. The 87% of the patients need
vasoactive drugs. The 47% need Swan-Ganz catheter to optimize the haemodynamic
management. The 77% presented a multiple organ disfunction syndrome (MODS) and
the 56% acute renal failure. The total mortality was 70%, basically due to MODS
(68%), while due to hypoxemia only in the 22%. The group treated with NO (the 35%
of the ARDS patients) were younger, without any other differences the patients
who did not received this treatment and with the same stage and mortality.
Patients who presented MODS, renal failure or hemodynamic unstableness presented
a higher mortality (p < 0.05).
PMID- 9658909
TI - [Prospective study of nosocomial infections in a medical ICU. A proposal for the
generalized use of the National Nosocomial Infection Surveillance System rates].
AB - OBJECTIVE: To know the more relevant nosocomial infection (NI) rates in our
Intensive Care Unit (ICU), risk factors associated with NI and trends in the
infective flora. METHODS: During a three-month period, the cumulative incidence,
density of overall incidence and device associated infection rates were
determined in a total of 308 patients admitted to the medical ICU, following the
recommendations of the National Nosocomial Infection Surveillance System (NNIS)
in the USA. RESULTS: The cumulative incidence was 8.4 infections per 100
admissions. The density of overall incidence was 12.9 nosocomial infections per
1,000 days of ICU stay. Device-associated infection rates were: 28.9 pneumonia
per 1,000 mechanical ventilation days, 5.3 urinary tract infections per 1,000
days of catheter use and 0.4 bacteremia per 1,000 days of central venous
catheter. Pneumonia was the more common NI, followed by urinary tract infection.
Pseudomonas aeruginosa was the microorganism recovered most frequently. The most
common used antibiotics were third generation cephalosporins, followed by
quinolones and macrolides. CONCLUSIONS: The use of NNIS rates is advisable
because its allows to know the impact of NI on our unit and to perform
comparative studies with other units of similar characteristics.
PMID- 9658910
TI - [Results of aortic valve replacement surgery in patients over 75 years of age].
AB - The increase in the mean populational age has increased the number of elderly
people eligible for cardiac surgery. The aortic pathology represents the most
common valvular pathology, mainly of degenerative etiology. The efficiency of the
aortic valve replacement in people aged over 75 years was studied, with
evaluation of hospital mortality, survival and functional class (NYHA). MATERIALS
AND METHODS: A total of 51 patients (25 males and 26 females, mean age 76.4 years
[range: 75-83]) underwent aortic valve replacement from October 1989 to February
1997. The most common condition was aortic stenosis (62.7%), followed by aortic
insufficiency (19%) and double aortic lesion (17%). Moreover, 31.3% of patients
required also coronary surgery with a mean of 1.1 grafts per patient. In 13.7% of
cases surgery on mitral valve was performed (1 commissurotomy, 1 mitral
prosthesis, 5 valve prostheses). In 10% of patients the procedure had to be
performed on an emergency basis. The functional class of patients prior to
surgery was NYHA grade III for 37% and grade IV for 10% of cases. The clinical
symptoms corresponded to angor in 15 cases (29.4%) and syncope in four cases
(7.8%). In nine patients the left ventricular ejection fraction prior to surgery
was below 50%. Aortic bioprostheses were implanted in 86.2% of cases. RESULTS:
The hospital fatality rate was 13.7% (7 cases). In the univariate analysis the
following mortality risk factors reached statistical significance: left
ventricular ejection fraction prior to surgery below 50%, associated surgery and
size of aortic prosthesis. In the multivariate analysis the following risk
factors were significant: left ventricular ejection fraction prior to surgery
below 50% and associated mitral surgery. The follow-up was performed in 100% of
patients, with a mean time of 29.6 months. One patient died during follow-up. The
functional class was NYHA grade I in 95.2% of cases. The actuarial survival,
including hospital mortality, was 84.2% at 5 years. CONCLUSIONS: Despite a higher
mortality in the aortic valve replacement surgery in patients aged over 75 years
compared with general population, results, long-term survival and life quality of
patients, renders surgery a non refusable first option as therapy for aortic
valve pathology in this age group. Nevertheless, avoiding the deterioration of
preoperative left ventricular function is imperative, mainly in those cases with
concomitant mitral pathology, as both factors significantly contribute to an
increase in mortality in this group.
PMID- 9658911
TI - [Safety of oral anticoagulation in aged patients with heart diseases].
AB - BACKGROUND: Anticoagulation therapy in the elderly poses some doubts on the
possible increase in hemorrhagic risk. The hemorrhagic complications in a
population of patients over 70 years of age anticoagulated with acenocoumarol by
heart disease were studied. MATERIALS AND METHODS: A study was made of seventy
two patients (43 females and 29 males; mean age: 73 years) anticoagulated for one
year and controlled on an outpatient basis by means of INR (international
normalized ratio) measurement with a maximal interval of four weeks. INR values
above 4.5 or below 2.0 were considered out of range. RESULTS: Nineteen patients
had an INR above the recommended value on one occasion and eleven patients on two
or more occasions. Sixteen patients had hemorrhagic complications, five were
admitted on account of hemorrhages although none of them required transfusional
therapy. No cases of brain hemorrhage or peripheral embolism occurred.
CONCLUSIONS: Most anticoagulated elderly patients were within their therapeutic
range. The percentage of severe hemorrhagic complications was low. Advanced age
had did not prove to be a factor against therapy with oral anticoagulants.
PMID- 9658912
TI - [Thyroid lymphoma: a not so unusual disease].
AB - A review was made of the six cases of primary thyroid lymphoma diagnosed at our
institution. An increase in the incidence was observed of this disease in the
last two years, with no evidence of lower diagnosis of anaplastic thyroid
carcinoma. The presenting symptom was compression in all cases. The interval time
from symptoms to diagnosis ranged from 5 to 150 days. The centroblastic pattern
was the most common histologic type, with a relevant role of MALT lymphoma in the
last few years. Therapy included surgical exeresis in two cases on account of
compressive symptoms and radiotherapy and/or chemotherapy was always preferred on
account of the stage.
PMID- 9658913
TI - [Hepatitis C in health personnel].
PMID- 9658914
TI - [Thyroid cancer: metabolic treatment and follow-up using thyroglobulin levels and
I-131 gammagraphy].
PMID- 9658915
TI - [Proliferative glomerulonephritis and dyspnea in a 70-year-old male patient].
PMID- 9658916
TI - [Correction of drug dose in patients on hemodiafiltration].
PMID- 9658917
TI - [Abdominal pain in a young man].
PMID- 9658918
TI - [Adult respiratory distress syndrome with fatal outcome after status
asthmaticus].
PMID- 9658919
TI - [Young woman with tuberous sclerosis and spontaneous pneumothorax].
PMID- 9658920
TI - [Digital gangrene, osteomyelitis and pneumonia in a young parenteral drug abuser
female patient].
PMID- 9658921
TI - [Hyperkalemic myopathy and Addison's disease].
PMID- 9658922
TI - [Hypertensive crisis and vesical mass].
PMID- 9658923
TI - [Pseudomyotonia as initial manifestation of primary hypothyroidism].
PMID- 9658924
TI - [Macroangiopathic anemia secondary to aspergilloma associated with idiopathic low
CD4 syndrome].
PMID- 9658925
TI - [Wernicke's encephalopathy: an alternative diagnosis in oncologic patients].
PMID- 9658926
TI - [Rendu-Osler-Weber disease. Nontraumatic hemothorax and pulmonary sarcoidosis].
PMID- 9658927
TI - Spontaneous cytokine gene expression by cultured skin fibroblasts of systemic
sclerosis. Correlation with collagen synthesis.
AB - OBJECTIVE: To investigate the spontaneous cytokine gene expression in fibroblasts
from patients with diffuse cutaneous systemic sclerosis. Their pattern of
expression was correlated with the production of collagen. METHODS: Fibroblasts
were obtained from skin biopsies of nine patients diagnosed with systemic
sclerosis (mean 16 +/- 8.7 years of disease duration) and ten control
individuals. The cytokine gene expression was detected by coupled reverse
transcriptase polymerase chain reaction for interleukins 1 beta, 6, 8, tumour
necrosis factor-alpha, and transforming growth factor beta. In addition, collagen
synthesis was measured by [14C]-proline uptake in fibroblast cultures. RESULTS:
All fibroblast samples from patients expressed the interleukin-6 gene (p = 0.04
compared with controls). Eight of the nine patients expressed interleukin-8 (p =
0.02 compared with controls). Four of them expressed also transforming growth
factor beta and two more weakly expressed the tumour necrosis factor-alpha gene.
Only one patient showed transcription for the interleukin-1 beta gene. In
accordance with such immune activation, collagen synthesis was higher in
fibroblasts from patients with systemic sclerosis (p = 0.028) as compared with
normal controls. Indeed, a positive correlation was found between the expression
of IL-6 gene and collagen production (rs = 1). CONCLUSION: The constitutive
expression of IL-6 and IL-8 genes by fibroblasts may play an important role in
the perpetuation of local immune dysregulation, thus leading to a permanent
fibroblast activation in patients with systemic sclerosis.
PMID- 9658928
TI - [Risk factors in the epidemic neuropathy of Cuba].
AB - OBJECTIVE: A case control study to find out if Cuba's epidemic neuropathy was a
result of one of the following causes: (1) an infectious process, (2) exposure to
one or more toxical agents, (3) low intake of one or more nutrients, or (4) more
than one of such causes and their interactions. MATERIAL AND METHODS: A total of
311 cases of epidemic neuropathy with optic and peripheral symptoms and 377
controls were studied. A questionnaire with 55 items was employed to document
exposure to factors determined by the etiologic hypothesis. Data analysis was
done separately for the optical and peripheral types of the disease. RESULTS: No
association was found between illness and any deficiency of basic sanitation for
both types of neuropathy. Acute stress, irregularities in food intake, body
weight loss in the last 12 months and other indicators of nutritional
deficiencies were associated to both clinical manifestations, although they were
also high in the controls. Low frequency of illness was found for people living
with diseased persons. Females had a significant high risk of illness in the
peripheral manifestations whereas smoking was the only toxical risk factor in
optical neuropathy. Nutritional deficiencies together with unidentified personal
factors were the main associations for illness outcome; smoking increased
significantly the risk of optical neuropathy. CONCLUSIONS: 1. The infection
etiology was unsupported in the study. 2. Smoking appeared as a factor for the
optical neuropathy. 3. Stress induced by vital events were significantly
associated with the disease. 4. Both types of the neuropathy were associated to
body weight loss and other indicators of nutritional deficit.
PMID- 9658929
TI - [Vitamin D induces proliferation in rat endometrium cultured cells].
AB - OBJECTIVE: To study the effects of 1,25-dihydroxyvitaminD3 (1,25-(OH)2D3) on
proliferation and cell death in the rat uterus. MATERIAL AND METHODS: A rat
endometrial cell line (Rentro 1) grown in a Dulbecco Minimal Essential Medium
(DMEM) supplemented with 1% charcoal stripped serum was used in all experiments
in order to eliminate the steroid hormone. Cell monolayer was incubated in the
presence and absence of 1,25-(OH)2D3 or 17 beta-estradiol or vehicle. After
stimulation, we evaluated cell proliferation and DNA synthesis by trypan blue
counting method and flow cytofluorometry, respectively. Finally, the genomic DNA
integrity was evaluated by electrophoresis and the bands visualized with
ultraviolet light. RESULTS: The cells in medium containing 1% fetal bovine serum
free of steroid hormones stimulated the cell growth 85% more than without serum.
Supplement with albumin did not allow cell growth. The cells did not respond to
17 beta-estradiol but the presence of 1,25-(OH)2D3 induced cell proliferation.
These results confirm that Rentro 1 cells do not express the estrogen receptor
and demonstrate their capacity to respond to 1,25-(OH)2D3. Finally, the integrity
of DNA was not affected by 1,25(OH)2D3, suggesting that this hormone is not
involved in cell death by apoptosis in our cell line, as seen in other cell
lines. CONCLUSIONS: 1) 1,25-dihydroxyvitamin D induced cell proliferation in the
endometrial cell line Rentro 1 in a dose-dependent fashion and this effect is
independent of the presence of an estrogenic stimulus; 2) the increase in cell
number was related to DNA synthesis during the cell cycle; and 3) the presence of
the hormone in the culture medium was not able to induce cell death.
PMID- 9658930
TI - [Anemia and iron deficiency in 490 Mexican pregnant women].
AB - OBJECTIVE: To explore correlations of sociobiological variables with levels of
blood hemoglobin (HB) in 490 pregnant women. SETTING: Women attending private
practice and two public hospitals in the city of Leon, State of Guanajuato (1800
m above sea level). MATERIAL AND METHODS: Demographic, obstetric, nutritional and
socioeconomic data were obtained together with an EDTA-blood sample for CBC, and
serum for metabolite assays. The women had a mean gestation of 25 weeks (range 4
40) and 65% were multiparous with a mean parity of 2.1. By Mexican standards they
had fairly high social, nutritional and intergenesic lapse. Associations were
explored by step-wise multiple ANOVA. RESULTS: On the basis of HB < 12 g/dL
(equivalent aprox to 11 at sea level), 37% of the women were considered anemic.
The MANOVA (excluding iron deficiency) showed associations of HB with gestation
(p < 0.001) and parity (p = 0.024). Iron deficiency was present in 76% of the
anemics (136/180) and 31% of the non-anemics (97/310). Folate and vitamin B12
assays in women with anemia and no iron deficiency showed folate or B12
deficiency in only 33% (14/43) leaving 29 cases with anemia of unknown etiology.
CONCLUSIONS: 1. Gestation age was the factor most strongly associated to anemia
and iron deficiency in our sample. 2. Anemia and iron deficiency were seen in 37%
(N = 180) and 48% (N = 233) of the women respectively. 3. Of the 180 anemic
women, 76% (N = 136) were iron deficient but only 14/43 anemic without iron
deficiency were folate or B12 deficient leaving 6% (29/490) with anemia of
unknown etiology. 4. The prevalence of anemia and iron deficiency were high in
our population in spite of its fairly good sociodemographic and nutritional
conditions.
PMID- 9658931
TI - [Laparoscopic splenectomy in autoimmune thrombocytopenic purpura].
AB - OBJECTIVE: To describe the perioperative characteristics, complications and
outcome of the first 22 patients who underwent laparoscopic splenectomy for
refractary/recurrent ITP in our institution. MATERIAL AND METHODS: Clinical and
biochemical characteristics, spleen size, indication for surgery, operative time,
blood requirements, complications and outcome of 22 patients who underwent
laparoscopic splenectomy between 1994 and 1997 were prospectively recorded. Their
mean age was 40 +/- 15 (+/- SD), 15 females and 7 males. RESULTS: The
preoperative platelet count was 56 thousand +/- 58.7/uL, average spleen size 10.5
+/- 2 cm. The surgical time averaged 4.5 +/- 1 hours; accessory spleens were
removed from two patients. Conversion to the open procedure was necessary in two
cases. Complete response was achieved in 59%, partial response in 27%, and no
response in 14% (none of these due to missed accessory spleens). Six patients
developed complications. One of them died two days after surgery. The mean
postoperative stay was 4.7 +/- 2.6 days. CONCLUSIONS: The results of laparoscopic
splenectomy were similar to our previous results with the open approach. The
laparoscopic technique took longer in our hands but the postoperative stay was
shorter.
PMID- 9658932
TI - [Survey of climacteric symptoms in semi-rural areas of Yucatan].
AB - OBJECTIVE: To determine the symptoms of climacterium in women from rural areas of
Yucatan. MATERIAL AND METHODS: We conducted a transversal study of 202 women in
the villages of Seye and Cuzama. A questionnaire on socioeconomic status, and
symptoms of the menopause was applied. RESULTS: In both villages, the commonest
menopause-related symptoms were backache tiredness in more than half of the
women. Sweating and hot flashes were reported by 35% and 31%, respectively.
CONCLUSION: Our observations differed from the absence of hot flashes and
sweating reported by another group in rural women living in Yucatan (Ref 7).
PMID- 9658933
TI - [Otoneurologic abnormalities in insulin-dependent diabetes].
AB - OBJECTIVE: To assess the auditory and vestibular function in patients with
diabetes. MATERIAL AND METHODS: We studied and followed for three years, 10
patients (6 females) of 20.6 years of age (SD 5.5 years), with insulindependent
diabetes mellitus of 9.5 years (SD 3.7 years). The patients were selected for
having peripheral neuropathy without prolipherative retinopathy and otologic
disease or individual factors which could cause neurootologic symptoms. Their
glomerular filtration rate and renal plasma flow were 150 mL/min (SD 50) and 543
mL/min (SD 113). RESULTS: Initially all patients had normal audiologic responses,
including auditory brainstem responses, but had abnormally and simetrically
diminished horizontal vestibulo-ocular responses. A year later one patient had
vertigo and asymmetric vestibulo-ocular responses. In the third year, another
patient showed similar abnormalities and a third one showed sensorineural hearing
loss. CONCLUSION: Our results suggest that patients with insulindependent
diabetes mellitus may suffer neuro-otological deterioration.
PMID- 9658934
TI - [Observer variability in the radiologic interpretation of interstitial lung
disease].
AB - OBJECTIVES: To study intra and interobserver variability of two pediatric
neumologists in X-ray readings of interstitial lung disease (ILD), to determine
the effect of clinical data on the readings, and to evaluate their interpretation
in terms of the histopathology diagnosis. DESIGN: Prospective, cross sectional,
comparative, blinded. SETTING: The Instituto Nacional de Pediatria of Mexico
City. MATERIAL AND METHODS: Chest X-rays of 45 ILD pediatric patients with
diagnosis confirmed by open lung biopsy were read by the two observers three
times at two weeks intervals and in a randomized fashion. The observers were
blinded to previous readings of both observers as well as to the diagnosis. The
first two readings were done with no clinical information given to the observers,
but some was given for the third reading (age of inception, length of evolution,
and main symptoms at time of the X-rays). A classification in one of 5 patterns
(lineal, reticular, reticulonodular, grounded glass, honeycomb) was established
by the observers. Associations of patterns with anatomopathological diagnosis was
explored. Weighted kappa was used in the statistical analysis. RESULTS: With one
exception, good agreement (Kw 0.57-0.88) was found intra and interobservers.
CONCLUSION: We believe the low variability is the result of the 15 years of
shared experience of the two observers participating in this study.
PMID- 9658935
TI - Two cases of psychogenic purpura.
AB - Psychogenic purpura, also known as recurrent painful bruising or autoerythrocyte
sensitization syndrome (Gardner-Diamond syndrome) is usually associated with
emotionally disturbed patients. It is a troublesome entity for both patient and
physician since extensive work-ups yield no diagnosis. We describe two females in
their early twenties with recurrent painful bruising and diverse accompanying
symptoms which appeared after physical trauma. One of the patients developed a
bruise after intradermal injection of her own blood (with no reaction to saline
injection). One patient had a personality (borderline) disorder, the other a
factitious disorder. Punch biopsies revealed a perivascular inflammatory
infiltrate, erythrocyte extravasation and no vasculitis. Psychogenic hemorrhagic
disorders are uncommon yet must be considered in the differential diagnosis of
purpura. Patients are usually young emotionally troubled females who present
painful recurrent bruises on extremities frequently after trauma or surgery.
Autoimmune mechanisms and increased cutaneous fibrinolytic activity have been
implicated, although further studies are needed. Correct diagnosis is important
to avoid aggressive and even mutilating treatments, and an adequate comprehension
of these purpuras is important for the attending physician.
PMID- 9658936
TI - [Ten cases of Ciguatera fish poisoning in Yucatan].
AB - BACKGROUND: Ciguatera fish poisoning is a clinical syndrome associated with the
consumption of contaminated fish. The clinical picture is a constellation of
gastrointestinal, neurologic and cardiovascular symptoms. AIM: To report 10 cases
of ciguatera poisoning in our country. METHOD: We recorded the clinical course
during the severe acute symptoms with a follow up of 34 months. RESULTS: The time
between the ingestion of contaminated fish and symptoms varied from 20 minutes to
12 hours. All suffered gastrointestinal disturbances as the main manifestation.
Watery diarrhea was the earliest complaint. Cold-to-hot temperature reversal
dysesthesia occurred in all but there were differences in the occurrence of
nausea, vomiting, cramping, abdominal pain, weakness, paresthesia, arthralgia,
myalgia, dizziness, dysuria, dyspnea, headache, pruritus, lip numbness, dry
mouth, dental pain, chills, tremors, fasciculations, blurred vision,
hypersalivation and dysphagia. CONCLUSION: 1. There were some differences in the
clinical picture of our cases mainly in the initial symptoms and their severity.
2. Gastrointestinal symptoms were the most common complaint. 3. We did not find
associations between the amount of toxic fish ingested with the latency period
and the severity and duration of the symptoms.
PMID- 9658937
TI - [Two cases of colonic lipoma as a cause of rectal prolapse].
AB - Two cases of submucosal colonic lipomas presenting as rectal prolapse are
described. Both of them required resection by laparotomy. Colonic lipomas are a
uncommon entity and they have not been documented as a cause of rectal prolapse.
PMID- 9658938
TI - [The genetics of Alzheimer's disease].
AB - Alzheimer's disease is a degenerative disorder of the central nervous system
which causes progressive memory and cognitive decline during mid to late adult
life and is accompanied by a wide range of neuropathologic features including
extracellular amyloid plaques and intra-neuronal neurofibrillary tangles. Four
genetic loci for Alzheimer's disease have been identified. They are the amyloid
precursor protein gene on chromosome 21, a gene for early onset autosomal
dominant form on chromosome 14, another gene on chromosome 1, and the risk
modifying gene apolipoprotein E on Chromosome 19. The etiology is heterogeneous
and complex, and additional Alzheimer's disease genes remain to be found. The
genes identified in the inherited forms are now being used to understand the
pathogenesis of the disease.
PMID- 9658939
TI - [Abnormal hemoglobins and thalassemias in Mexico].
AB - The distribution of abnormal hemoglobins in Mexico is derived from surveys and
from the study of patients with hemolytic anemia. In aboriginal populations, more
than 3,000 individuals have been studied: structural abnormal hemoglobins are
virtually absent in Mexican Indians and the sporadic finding of hemoglobin S
among them is due to admixture with Africans brought as slaves during the Spanish
domination; two new variants of hemoglobin (Mexico and Chiapas) were found in
aborigines. The surveys in hybrid groups in selected areas of the country show
that in some West and East Coast communities there are different frequencies of
Hb S heterozygous, and that a high prevalence of Hb S trait has been found in
some communities similar to that in some African areas. In a group of 200
subjects of a town located along the Gulf of Mexico Coast, 6% of Hb S and 15% of
thalassemia beta heterozygous is observed. In hospital surveys in two cities
(Guadalajara and Puebla) several abnormalities of hemoglobin have been identified
(C, SC, Riyadh, Baltimore, Tarrant, Fannin-Lubbock and Mexico). In the study of
isolated cases, mainly of patients with hemolytic anemia, hemoglobins I
Philadelphia, G-San Jose and D-Los Angeles are seen. The thalassemias are the
more frequent hemoglobin abnormalities in selected populations of our country. In
a community of Italian ancestry a frequency of 1.3% of beta thalassemia trait is
found. In our laboratory, 76% of the abnormalities are cases of beta thalassemia
trait. Patients with Hb H disease, beta thalassemia (homozygous and heterozygous)
and combinations of these abnormalities with hemoglobins S, Hb S + hereditary
persistence of fetal hemoglobin (HPFH) and Hb E as well as families with delta
beta thalassemia, HPFH and Hb Lepore-Washington-Boston have been also detected.
PMID- 9658940
TI - [Genetic heterogeneity and phenotypic variability in 46,XY sex reversal].
AB - The discordance between the chromosomic and the gonadal-phenotypic sex is known
as sex reversal (XX males and XY females). We review the XY pure gonadal
dysgenesis characterized by female phenotype, primary amenorrhea and absence of
secondary sexual development. Bilateral streak gonads are always present in the
complete form of this syndrome, while variable degrees of virilization are found
in the partial forms, depending on the severity of the testicular damage. A
plausible explanation for this pathology are SRY mutations that interfere with
the testicular differentiation. However, only 10-15% of the patients with the
complete form show SRY mutations, particularly in the HMG box. The remaining
cases are probably due to mutations in different autosomal or X-linked genes
which are also involved in the sex differentiation cascade. Recently, it has been
shown that mutations in several genes responsible of well known genetic entities
as WT1, SOX9, DSS and SF1, result in sex reversal. These findings reveal the
genetic heterogeneity and clinical variability of XY sex reversal and provide the
basis establishing a hierarchy of genes and their participation in the sex
determination pathway.
PMID- 9658941
TI - [The difficulties of scientific journals in Spanish].
PMID- 9658942
TI - [Experimental endocarditis. Pathological anatomy of human endocarditis].
AB - Experimental reproduction of human endocarditis in animal models has been based
on the induction of structural lesions in valve endocardium using different
methods. The primary lesion caused in this way is the so called non-bacterial
thrombotic endocarditis. Its colonization is then induced by inoculation of
microorganisms in the bloodstream. Freedman's modified method has been the most
widespread model of this type. It has mainly been performed in rabbits with
inoculation of Staphylococcus aureus or alpha-hemolitic Streptococcus.
Experimental models of endocarditis have contributed to our knowledge of the
pathogenic mechanisms, causative agents and predisposing factors of endocarditis.
They have also allowed us to develop appropriate diagnostic, therapeutic and
prophylactic measures for its management.
PMID- 9658943
TI - [Etiopathogenesis of infective endocarditis: predisposing heart diseases and
causal microorganisms].
AB - Infective endocarditis is caused by the infection of an amorphous mass of
platelets and fibrin (the so-called nonbacterial thrombotic endocarditis) which
involves a damaged endothelial surface of the heart. Several pathogenetic
mechanisms (hemodynamic, immunological, microbiological, etc.) are needed for the
development of endocarditis. We review some of these mechanisms, as well as
possible changes in etiopathogenesis of this disease that have recently occurred.
PMID- 9658944
TI - [Clinical manifestations of infective endocarditis].
AB - Infective endocarditis has a broad clinical picture, with systemic and multiorgan
impairment. The organs most frequently involved are the heart, the central
nervous system and the kidneys. Complications are caused by several mechanisms:
direct effect on the heart, septic embolisms and immunological phenomena. We
review some of the main clinical aspects of this disease, as well as the results
of a wide series of patients with infective endocarditis from our hospital.
PMID- 9658945
TI - [Laboratory control in diagnosis and treatment of infective endocarditis].
AB - Infectious endocarditis is caused by a wide variety of microorganisms.
Etiological diagnosis depends either on direct methods, directed to the detection
and isolation of the causative organisms, or serological methods. Blood cultures
remain as the best method for the diagnosis of bacterial endocarditis. Blood
culture technology has changed due to the appearance of new automatic continuous
monitoring systems which shorten the detection time. Endocarditis with a negative
blood culture has decreased below 5% because of new blood culture systems, new
serological methods and molecular technology. The control of antimicrobial
therapy in endocarditis must be performed by expert laboratories. A minimal
bactericidal concentration, serum levels of antimicrobials and the serum
bactericidal test are the most useful parameters. Their execution requires the
use of strict protocols and interpretation must be carried out with an expert in
clinical microbiology and infectious diseases.
PMID- 9658946
TI - [Diagnostic criteria of infective endocarditis: from Von Reyn to Duke.
Transthoracic and transesophageal echocardiography].
AB - The Von Reyn criteria determine only a small number of definitive diagnoses of
infectious endocarditis, while it is mainly diagnosed by histopathological
confirmation in surgery or autopsy. This necessitates carrying out a new
diagnostic scheme with accurate sensitivity and specificity based on rigorous
clinical support. This scheme is provided by the Duke University criteria, which
enhance the role of conventional and transesophageal echocardiography, in the
diagnosis of infectious endocarditis. Echocardiography is the only accurate
procedure for a non invasive diagnosis of vegetation, the main lesion in this
pathology. Often, tissue destruction causes regurgitation, which is responsible
for hemodynamic impairment or allows the spread of the infectious process to
perivalvular tissue and can form an abscess. These complications and many others,
which are difficult to treat, require an early diagnosis of this disease.
Sensitivity of transesophageal technique to detect vegetations and complications
is higher than that observed in conventional echocardiography, above all in
patients with prosthetic valves. If the transesophageal study is negative, the
existence of an infectious endocarditis is quite unlikely. Nevertheless, we need
to consider clinical features, as the specificity of this technique is moderate.
PMID- 9658947
TI - [Natural history and prognosis in infective endocarditis].
AB - The natural history and prognosis of native valve infective endocarditis,
prosthetic endocarditis and right sided endocarditis in drug addicts is analyzed.
In native endocarditis mortality during the active phase is 12% and survival at
10 years 81%. Early prosthetic endocarditis has a worse prognosis. In late
prosthetic valve endocarditis prognosis depends on the infective organism:
mortality is less than 10% in estreptococcal infections and higher than 50% in
staphylococcal infections. Right sided endocarditis in intravenous drug addicts
has a relatively benign prognosis and seldom requires surgical treatment.
PMID- 9658948
TI - [Is prophylaxis needed? Is it really effective? Risk of endocarditis after heart
surgery].
AB - Infective endocarditis still has an important morbidity and mortality in the
acute phase and also in the following years. Because of this, the development and
use of preventive strategies have been an important target in developed
countries. Until we have some prospective studies their use will be only
intuitive and based on the following criteria: endocarditis frequently follows a
bacteremia; some diagnostic or therapeutic procedures cause bacteremia; the germs
are habitually predictable in each procedure and are sensitive to specific
antibiotics; patients with some cardiac or major structural defects have a higher
risk of endocarditis. For these reasons, a rational treatment is to give the
specific antibiotic against the microorganism prophylactically before it enters
the bloodstream during the procedure. Although available data are inconclusive
and sometimes even contradictory, most authors recommend the indication of
prophylactic measures whose efficacy depends on three basic points: a)
identification of patients with a high risk of endocarditis, especially those
with a prosthetic cardiac valve; b) knowledge of procedures that need
chemoprophylaxis, especially dental and oral procedures, and c) selection of the
best prophylactic policy in each specific case. In summary, it is necessary to
know to "whom", "when" and "how" to apply prophylactic measures. There are some
special situations that must be considered carefully: patients treated with
anticoagulant drugs or with a cardiac pacemaker or with an implanted
defibrillator, patients with renal insufficiency and an arteriovenous fistulae,
and some patients needing open heart surgery, or those who have already had open
heart surgery. In conclusion, the prevention of bacterial endocarditis using
antibiotics is currently practiced in clinical settings, especially in some
specific groups of patients. It is necessary to recommend this treatment in high
risk patients (i.e. in those with prosthetic cardiac valves) before a high risk
procedure (i.e. dental procedures known to induce gingival or dental bleeding,
including professional cleaning) and in medium risk patients, the indication must
always be based on an individual analysis according to American Heart Association
guidelines.
PMID- 9658949
TI - [Drug treatment of native valve infective endocarditis in patients not addicted
to parenteral drugs].
AB - Infectious endocarditis is an infection that is characterized by the presence of
microorganisms in dense populations in vegetating lesions in the endocardium.
Because phagocyte penetration to the interior of the vegetation is practically
impossible, to cure infectious endocarditis, high doses of bactericidal
antibiotics are administered, usually intravenously and for a long duration. In
this article, antibiotic treatment is reviewed, depending on the isolated
microorganism and in cases where necessary, treatment is initiated in an
empirical manner. Once the microorganism was isolated, the recommended guidelines
for antibiotic treatment have gone through some variations in recent years, due
to the changing pattern of antibiotic sensitivity of some microorganisms, to the
point of finding ourselves on occasion without an effective treatment (e.g.
multiresistant enterococci). In addition, these variations are due to the
introduction of new antibiotics that allow, in special cases, for the treatment
to be administered on an outpatient basis. Using anticoagulation in infectious
endocarditis is still considered controversial. In general, only patients having
cardiac valvular prostheses seem to benefit from its use.
PMID- 9658950
TI - [Prosthetic valve endocarditis].
AB - Infective endocarditis occurs in 4% of prosthetic valve carriers. The infection
is related to both the injured endocardium and circulating microorganisms. Early
prosthetic endocarditis, occurring in the first 12 months after valvular surgery
is mainly caused by staphylococci, and late prosthetic endocarditis has a similar
etiology as native valve endocarditis. Clinical manifestations of early cases are
due to both bacteremia and prosthetic malfunction. In late cases the clinical
picture is similar to native valve disease. Mortality in prosthetic endocarditis
remains high, especially in early cases, despite combined medical and surgical
treatment.
PMID- 9658951
TI - [Infective endocarditis in the aged].
AB - This paper reviews the current questions and the new aspects related to Infective
Endocarditis in elderly patients. Four points are emphasized: a) epidemiological
changes during the last decades, b) clinical features and diagnostic challenges
of infective endocarditis in the elderly, c) mortality and prognosis, and d)
preventive and therapeutic measures that must be taken into account.
PMID- 9658952
TI - [Endocarditis in parenteral drug addicts. Right-sided endocarditis. Influence of
HIV infection].
AB - Infective endocarditis is a life-threatening infective complication in parenteral
drug abusers. The tricuspid valve is the structure most frequently affected and
Staphylococcus aureus the predominant microorganism. Fever, multiple pulmonary
emboli and sustained bacteremia by S. aureus are signs of clinical alert for
right-sided endocarditis in these patients. Echocardiography has developed a
significant improvement in diagnosis and the transthoracic mode has a
considerable reliability when high suspicion is established. Outcome is usually
favourable with mortality less than 10%. Recent studies have made shorter
treatments possible in selected patients and oral therapy is also considered. HIV
infection, in advanced status, may indicate a worse survival rate.
PMID- 9658954
TI - [Indications and surgical techniques in the acute phase of infective
endocarditis].
AB - Infectious endocarditis is increasingly resistant to antibiotic therapy, due to
the increasing number of patient with cardiovascular prostheses or those who are
severely immunosuppressed. Frequently, this syndrome and its complications can
only be solved with surgery. In this article, which is based on the international
literature plus own observations in 77 patients, the indications for surgery and
the different technical approaches during the acute phase of infectious
endocarditis are reviewed. Surgery to control infectious endocarditis is
indicated when there is one of the following situations: a) persistence of
infection despite an adequate antibiotic treatment, usually due to a specific
pathogen (Staphylococcus aureus, fungus, etc.) or to a low antibiotic penetration
into the infected issues (abscess); b) progressive hemodynamic deterioration due
to tissular destruction and development of valvular incompetence or fistulous
communications or c) development of other complications (repetitive embolism,
cardiovascular aneurysms, conduction blocks, etc.). Hemodynamic deterioration due
to heart failure refractory to medical treatment is the most frequent indication
for cardiovascular surgery, and this was present in 61% of our patients. The
timing for surgery is still controversial, although scheduling it at an early
stage is generally preferred. The specific surgical technique is chosen according
to the degree of tissular destruction and is aimed to remove the infected tissue
and to repair the damaged structures or, if this is not feasible, to implant
cardiovascular prosthesis.
PMID- 9658953
TI - [Infective endocarditis caused by unusual microorganisms].
AB - All series of infective endocarditis had a variable proportion of cases without
an etiologic agent because all cultures were negative. New microbiologic
techniques have permitted the discovery of the role of many microorganisms in
infective endocarditis. C. burnetii is an increasing causative agent of subacute
infective endocarditis. In the diagnosis, to the detection of antiphase-I
antibodies, immunohistochemical, molecular techniques and cellular cultures have
been added. Total cure is difficult to obtain. The combination of doxicicline
plus ciprofloxacin for at least 3 years has been proposed as the treatment of
choice. Surgery must be reserved for patients with cardiac insufficiency. Less
than 2% of cases of acute brucellosis are complicate with infective endocarditis.
Infective endocarditis produces serious and rapid valvular destruction with high
mortality rates if valve surgery is not performed. For medical treatment at least
3 active agents are required. Bartonella has recently been described as an
etiologic agent of infective endocarditis. It mainly affects to homeless people
living in poor hygienic conditions. The aortic valve is most commonly involved
and, frequently, valve insufficiency requires valve replacement. Blood culture
isolation needs long incubation periods. Parenteral nutrition, immunosuppression,
wide spectrum antibiotic regimens, intravenous drug addiction and cardiovascular
surgery are risk factors previously described in the development of fungal
endocarditis. C. albicans and Aspergillus spp. are most frequent etiologic
agents. Infective endocarditis should be suspected in any patient with systemic
fungal disease. Blood cultures are often negative except for Candida spp.
Peripheral emboli and large vegetations are frequent. Mortality is high,
antifungal therapy combined with surgery is the treatment of choice. Legionella,
Mycoplasma, Chlamydia, Mycobacteria, viruses are potential agents of infective
endocarditis, and difficult to diagnose because of special culture requirements.
Epidemiological clues, serologic and molecular techniques and blood cultures
could identify them.
PMID- 9658955
TI - [Aortocoronary bypass without extracorporeal circulation].
AB - Extracorporeal circulation is nowadays part of the standard technique of
aortocoronary reconstruction. The authors summarize in their paper their
experience with operations in 45 patients where an aortocoronary bypass was made
on the beating heart without the use of extracorporeal circulation. None of the
patients died. The incidence of postoperative complications was low. Rapid
rehabilitation of the patients and a shorter period of hospitalization makes this
method an alternative standard technique of aortocoronary reconstruction.
PMID- 9658956
TI - [The clinical picture of acute appendicitis in children].
AB - The authors describe 3860 child patients operated on account of acute
appendicitis and analyse the data with regard to age, sex, year of incidence and
surgical finding. The highest incidence of acute appendicitis is between 8 and 11
years with a peak at the age of 10 years. It is more frequent in boys (58.3%)
than in girls (43.7%), the ratio being 1.3:1. It occurs more often during the
cold months (46.5%), in autumn (27.3%) and in winter (25.7%). The number of
gangrenous appendicitis is 34.7%-56.7% in boys and 43.5% in girls. The highest
rate of missed appendicitis is at the age of the highest incidence (15.2%) with a
peak at the age of 10 years (17.8%) and in January (13.3%). The highest incidence
of perforated appendicitis is also at the age of the highest incidence (14.9%)
with the peak at the age of 8 years (15.6%) and in June (13.5%). Perforation is
more frequent in boys (58.1%) than in girls (49.9%). The number of "negative"
appendicitis is 15.8%. Prevention of acute appendicitis still remains open due to
lack of knowledge of its etiopathogenesis.
PMID- 9658957
TI - [The significance of cytokines in the early diagnosis of postoperative
intraabdominal sepsis].
AB - The objective of the investigation was to evaluate the possible use of selected
cytokines and cytokine receptors in the early diagnosis of postoperative
intraabdominal sepsis. The investigation was focused on the dynamics of plasma
levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2,
IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the
receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on
model operations (resection of large bowel and resection of pancreas). These two
groups were compared with values recorded in patients with sepsis and with
healthy subjects. Based on the assembled results the authors recommend to use for
postoperative investigations the first 48 hours and to follow up the following
parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators
differentiate sufficiently specifically incipient sepsis from an uncomplicated
postoperative condition. During the subsequent period, i.e. more than 48 hours
after surgery, it is useful to include in the examination pattern also some acute
stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which
differentiate sepsis between the 3rd and 5th day after surgery.
PMID- 9658958
TI - [Reconstructive surgery of the aortic valve in rheumatic stenoses].
AB - Recently the number of plastic operations of the cardiac valves is increasing.
The authors present an account on 10 patients with stenosis of the aortic valve
where they performed a reconstruction without the necessity of a prosthesis.
Commissurotomy and rasping can be performed in patients when the basic anatomical
shape and dimensions of the valve are preserved. None of the patients died, one
was successfully reoperated on account of aortic insufficiency. The authors
describe and discuss the tactics and technique of the operation. They discuss the
possibility of reconstruction of the aortic valve in patients indicated for
aortocoronary reconstruction where the aortic defect appears to be of minor
impact.
PMID- 9658959
TI - [Various technics in the surgical treatment of dissection of the thoracic aorta].
AB - During 1994-1996 at the Clinic of Cardiovascular and Transplantation Surgery of
IKEM 17 patients were operated with acute dissection of the thoracic aorta type
A. Based on the applied surgical tactics the patients were retrospectively
divided into two groups. The first included 8 patients where surgical
reconstruction of the ascending aorta was implemented in the standard way, the
second group comprised 9 patients where the method of deep hypothermia and
circulatory arrest were used. Three operated patients died, all from the group
with deep hypothermia. The cause of death was twice multiorgan failure and once
haemorrhage in a female patient with cardiac tamponade before surgery. The
authors discuss the advantages and some pitfalls of surgery in deep hypothermia
and circulatory arrest and maintain that neurological disorders are most serious.
In the conclusion they draw attention to some possible ways how to improve
hitherto achieved results. They include e.g. reduction of the time interval
between the development of symptoms of dissection and surgery, careful checking
of the cooling and heating when using deep hypothermia, as well as better
prevention of cerebral embolic attacks.
PMID- 9658960
TI - [Techniques and tactics in multiorgan harvesting].
AB - The eighties and nineties are characterized by potent development of
transplantology. Despite this the number of patients with organ failures waiting
for a suitable organ is steadily increasing. Due to the permanent shortage of
donors transplantation surgery tries to implement the maximum possible multiple
organ collection. In the conclusion the authors emphasize the importance of
satisfactory cooperation of the anaesthesiologist attending donors and the organ
collection teams.
PMID- 9658961
TI - [Modern cardiac anesthesia].
AB - Contemporary cardioanaesthesia is based on the use of opioid effects, whereby
their dosage is steadily decreased. This calls for supplementation of anaesthesia
by further pharmacological preparations which ensure adequate anaesthesia.
Despite great efforts, neither, substances available at present nor their
combinations are sufficient to suppress surgical stress completely. The authors
attempt therefore selective influencing of the sympathetic nerve. In this respect
preparations which stimulate sympathetic alpha2 receptors seem promising. The
general trend of contemporary cardioanaesthesia is an effort to reduce the time
spent by patients in the intensive care unit to a minimum. The motivation are in
the first place economic reasons.
PMID- 9658962
TI - [Techniques, tactics and organizational aspects of distant procurement of donor
hearts for transplantation. Experience at the Department of Cardiovascular and
Transplantation Surgery of IKEM with 100 distant procurement of donor hearts].
AB - Transplantation of the heart is currently an accepted therapeutic method. One of
the factors which have an adverse effect on its availability is shortage of
suitable donors. Distant procurement of hearts helps to extend the number of
organs for transplantations. The authors present their experience with distant
procurement of donor hearts performed during more than three years. They evaluate
the influence of cold ischaemia time of the cardiac graft on early results of
cardiac transplantations. In the discussion they try to draw attention to some
problems associated with this technique for other organ retrieval teams
participating in multiple organ procurement.
PMID- 9658963
TI - [Spontaneous dissection of the left main coronary artery. Case report].
AB - The case report of a 59 years old woman present with spontaneous dissection of
the left main coronary artery including origins of its major branches is
described here. The patient had emergency surgery and a triple ACEG was
performed. The postoperative course was uneventful and a control angiogram proved
both complete graft patency and absence of previous dissection. Six months
following surgery the patient is doing well except for a minor effort dyspnea.
The available literary experience with this rare and potentially fatal coronary
condition is discussed in comments.
PMID- 9658964
TI - [Double gallbladder].
AB - The authors demonstrate on an exceptional case the possibility of laparoscopic
surgery in a patient with the rare finding of vesica fellea duplex. They also
draw attention to the algorithm of examination methods and possible errors in
these exceptional cases.
PMID- 9658965
TI - [Peripheral revascularization of the lower extremities in patients with critical
limb ischemia].
AB - The contemporary clinical approach to treatment of patients with critical limb
ischaemia is based on the conclusions of the European document adopted in
Rudeshaim in 1991 (Second European Consensus on Critical Limb Ischaemia). The
authors describe the comprehensive approach of different disciplines at their
department as the optimal therapy of this serious vascular disease.
PMID- 9658966
TI - [Heart interventions in Switzerland 1996].
AB - For the year 1996, as for the previous 11 years, a survey of cardiac invasive and
surgical procedures in Switzerland was carried out by a standardised
questionnaire. At the 25 Swiss centres (10 public non-university, 10 private and
5 university centres) a total of 12,183 coronary revascularisation procedures
were performed, 60% by percutaneous transluminal coronary angioplasty (PTCA). Of
all PTCAs, 88% were single vessel interventions. PTCA for ongoing infarction
accounted for 6% of all PTCAs. The use of coronary stents has increased to 50% of
all angioplasties. Other interventions like directional atherectomy and
rotablations have lost ground (0.4%, 35 cases). Only 22 interventions (0.2%) with
intracoronary laser devices were recorded. Among the new diagnostic tools, only
coronary ultrasound (233 cases) and Flowire (147) have been used regularly.
Percutaneous balloon valvuloplasties (60 cases) and catheter closure of
congenital shunt defects (42 cases) remained rare. Procedure related mortality
for PTCA was 0.6%, infarction occurred in 1.0% and emergency coronary artery
bypass grafting (CABG) became necessary in 0.4%. The total number of CABGs
(4,463) slightly decreased. Among the 2,677 non-coronary operations, 48% were
performed for valve disease and 51% for congenital heart disease. Heart
transplantation was performed in 41 patients (1%). Half of the interventional
catheter procedures were performed at the 5 university centres whereas the
majority of CABGs were carried out at private centres. Four centres performed
diagnostic procedures, exclusively. In-house surgical stand-by for PTCA was
available in 17 of the 21 interventional centres.
PMID- 9658967
TI - [Gunshot injuries in the head-neck area--basic principles, diagnosis and
management].
AB - Bullet wounds are a rare occurrence during times of peace. Recently, however,
there has been a general increase in the number and severity of this type of
trauma in our case load. First, the possible firearms and the individual types of
ammunition will be discussed. Based on this background, the possible types of
wounds are presented. Principally, one distinguishes ricocheting shots from
grazing ones, and those leaving bullets lodged in the body from those with
perforating wounds. The extent of tissue damage depends on internal lacerations,
on the compression of the tissue and on the temporary cavitation along the
projectile path. In contrast to other types of injuries, which are caused by a
blow or impact to the face or skull, gunshot traumas are characterized by an
irregular path, as well as, by localized destruction of bones with associated
effects. In this connection, the severity of the bullet wound also depends upon
the extent of involvement of the viscerocranium. As causes of gunshot wounds
during times of peace, suicidal intent, the negligent handling of firearms and
especially brutal crimes are those which come into consideration first and
foremost. The diagnostic aspect of firearm wounds, beside anamnesis, comprises
comprehensive X-ray diagnostics for a complete picture. From the therapeutic
side, tetanus serum and antibiotics as a prophylactic are recommended initially.
The operative treatment should take place depending on the injury with the
removal of a possible projectile. Bullet wounds always require an
interdisciplinary approach to treatment.
PMID- 9658968
TI - [Otogenic meningitis].
AB - We present three patients with otogenic meningitis, whose illness varied in
extent and clinical course. Meningitis and otitis media are associated in 19-22%
of all meningitis-patients. Streptococcus pneumoniae is the predominant
microorganism with hemophilus influenzae being the second most important. We
discuss the importance and problems of spinal puncture, early CT-scan as well as
further, more extensive and sophisticated examinations to exclude late
complications or predisposing factors. We emphasize an early start of antibiotic
treatment, which should not be delayed for diagnostic reasons. With the
appearance of highly penicillin-resistant pneumococci antibiotic therapy may
become more difficult in the future, but for the moment pneumococcal infections
in Switzerland can initially still be treated with cephalosporins or high dose
penicillin. The use of steroids, although of unproven efficacy, may be considered
in some cases. An otolaryngologist should initially be consulted for diagnostic
reasons as well as for possibly indicated early surgery.
PMID- 9658969
TI - [Missed somatic diagnoses--inexcusable, missed psychogenic somatic disorders--a
gentleman's offense].
AB - Overlooking somatic diagnoses is judged a serious failing, overlooking
psychogenic somatization a minor mistake. This situation derives from the medical
theory on which the physician bases his opinions, decisions and treatments. In
this case, the mechanistic model deriving from the introduction of physics and
chemistry into medicine in the 18th century. A 19 minute verbatim first interview
illustrates how the biopsychosocial interview method serves to pinpoint
psychogenic somatization in a woman who had been unsuccessfully examined and
treated for four years, bringing the underlying blocked process of grief to light
and making it the focus of therapy. Savings in time, cost and suffering are
obvious.
PMID- 9658970
TI - [Incidence of phlebography proven deep venous thromboses of the leg after knee
joint arthroscopy].
PMID- 9658971
TI - [Headache, cough, acute dyspnea and diffuse lung infiltration in a young woman.
Acute eosinophilic pneumonia].
PMID- 9658972
TI - [Fibromyalgia (generalized tendomyopathy) expert assessment practice].
PMID- 9658973
TI - [Erectile dysfunction].
PMID- 9658974
TI - [Organic basis of erectile impotence--evaluation and treatment possibilities].
AB - Sexual potency in its entire meaning implies: libido, erection, ejaculation which
are discussed in view of its incidence or loss. Organic reasons for erectile
dysfunction prevail at a high rate. These are listed regarding efficient
diagnosis and the therapeutic measures.
PMID- 9658975
TI - [Erectile dysfunction: psychological causes, diagnosis and therapy].
AB - For clinical practice, erectile dysfunction is the most important form of male
sexual disorders. In the majority of patients causation and course of their
erectile disorder is determined by a close interplay of somatic and psychosocial
factors. This psychosomatic interaction has to be taken into account during
diagnostic assessment and therapy. The old dichotomous concepts (psychogenic
versus organic) of erectile dysfunction have to be replaced by multidimensional
models that include dispositonal as well as chronifying factors. The main causes
of psychogenic erectile disorders can be divided into three groups, each
belonging to a different phase of time: 1. immediate factors (performance
anxiety), 2. antecedent life events from recent history, 3. developmental
vulnerabilities from childhood and adolescence. The most important instrument for
the psychological evaluation of sexually dysfunctional patients is a
comprehensive sexual history in which partner related aspects should be
particularly focused. In treating psychogenic erectile dysfunctions sex therapy
is a reliable and efficient treatment option with a reasonably good long-term
prognosis. In future, sex therapy should be combined with somatic treatment
options to reach a truly integrative approach to this complex disorder.
PMID- 9658976
TI - [Impotence: evaluation and treatment in general practice--what is reliable?].
AB - Erectile dysfunction has an incidence of 2-9% and it is seen often in general
practice. But the more recent treatment methods such as intracavernous drug
injections and vacuum constriction devices are not known by general practitioners
and normally used drug treatment has no efficacy. The management of impotence of
the general practitioner should concentrate upon internistic conditions like
diabetes, hypertension, hypercholesteremia and different drugs causing impotence.
The symptomatic treatment of erectile dysfunction has to be done by a specialist,
who is able to offer all therapeutic options.
PMID- 9658977
TI - [Measuring nocturnal tumescence--value in diagnosis of impotence].
AB - Nocturnal penile tumescence monitoring (NPT) is a non-invasive method to
differentiate between organic and psychogenic impotence. The routine use of NPT
monitoring in the evaluation of impotence is not effective due to its moderate
sensitivity and specificity with small therapeutic benefit and relatively high
costs. Patient's selection by intracavernous pharmacotest can improve the
efficiency of the investigation, so the method can help to secure the diagnosis
of a psychogenic impotence and then take effect on adequate therapy.
PMID- 9658978
TI - [Ambulatory treatment of erectile dysfunction].
AB - Intracavernous injection of vasodilating agents and vacuum constriction devices
are the therapeutic alternatives in outpatients with secondary erectile
dysfunction in Europe. The agents commonly used include papaverine, alprostadil
and phentolamine, singly or in combination. Quality of erectile response has
agent related characteristics and is dose-dependent. Optimal clinical response
ranges from full response for adequate sexual performance to a duration exceeding
patient's and partner's wishes. Therefore, the adequate response must be titrated
for every patient individually. Vacuum erection devices are efficacious and well
accepted from patients and their partners if they can accept the artificial
aspect of this approach. Vacuum erection devices are not suitable for men in
unstable relations. Injection therapy and vacuum device interfere with
spontaneity. The medicated urethral system for erection (MUSE) is a new approach
to deliver alprostadil to the corpus cavernosum. The application is more user
friendly than with injections but response rates for adequate satisfactory sexual
performance are lower than with intracavernous injections. Therefore indications
may be limited to specific etiologies such as neurogenic erectile dysfunction.
There is currently no efficient pill on the market although a wide range of
therapies are used. Approval and introduction of new oral treatments like
Sildenafil and others are awaited by patients and physicians. The availability of
new and highly efficient treatment options does not simplify evaluation and
treatment of patients with ED. In the contrary they request refinements in the
diagnostic process for etiologic diagnosis with subsequently least invasive
treatment and minimal side effects.
PMID- 9658979
TI - [Testosterone and impotence--when is androgen substitution advisable?].
AB - Testosterone and dihydrotestosterone play a critical role during embryogenesis of
the male genitalia. The development of secondary sex characteristics depends on
normal circulating androgen levels. They maintain libido and sexual potency.
Before testosterone supplementation men with erectile failure should receive
through hormonal investigation. Testosterone is useless in the treatment of
erectile problems in men with normal androgen levels. Testosterone can be
administered by intramuscular, oral or transdermal routes. Transdermal systems
produce serum testosterone levels closely mimicking the diurnal pattern described
in healthy young men. In elderly men during long term therapy, prostate specific
antigen should be measured regularly to anticipate malignant growth in the
prostate.
PMID- 9658980
TI - [Priapism].
AB - Priapism is the persistence of an erection that does not result from sexual
desire. Diagnosis is based on history, clinical examination, diagnostic
aspiration of blood and measurement of blood gas levels. The purpose of treatment
is to increase corporeal outflow by aspiration and injection of alpha stimulating
agents. In some rare cases selective angiographic embolisation or surgical
resection of a bleeding intracavernous artery is required. Prognosis is good if
diagnosis and treatment are not delayed.
PMID- 9658981
TI - [Induratio penis plastica].
AB - The symptoms of Peyronie's disease consist of fibrotic plaque formation, penile
deviation and painful erection. The etiology is still unknown. During its
progress the disease can cause erectile failure. The plaques mainly involve the
dorsal tunica of the penis. The diagnosis is made by palpation of the penis. The
ultrasound examination evaluates the plaque localization and possible
calcifications. Autophotography of penile deviation and duplex sonography of the
cavernous arteries used to measure arterial blood flow complete the diagnostic
efforts. Spontaneous remissions occur as well as chronic courses. Oral medication
is the first step in therapy. In cases with severe penile deviation leading to
disability to perform intercourse, persisting pain or erectile failure operative
management is indicated. Plaque surgery, modified corporal plication or
implantation of a penile prosthesis must be evaluated individually.
PMID- 9658982
TI - [New principle in therapy of erectile dysfunction: sildenafil].
AB - Erectile dysfunction may have psychological as well as a variety of organic
causes. This necessitates in each case a careful medical evaluation. Various
commonly used drugs, as well as alcohol and narcotics, may interfere with
erection and should, whenever possible, be discontinued before starting
treatment. Organic diseases should be identified and, if feasible, specially
treated. In the remaining majority of afflicted men, psychological treatment and
partner counseling may produce an improvement, but ultimately what is necessary
remains an effective and safe medication. The drug, Sildenafil, introduces a new
therapeutic principle. During sexual nerve stimulation, nitric oxide (NO) is
released from nerves into the cells of the penile erectile bodies. NO activates
in turn its "second messenger", the substance cyclic GMP, and the latter induces
the vasorelaxation and blood filling of the erectile bodies. Orally administered
Sildenafil competitively inhibits phosphodiesterase type 5, which physiologically
inactivates cyclic GMP in the erectile bodies. Thus, Sildenafil increases in men
with erectile dysfunction the NO-stimulated cyclic GMP concentration and,
thereby, improves erection. This new therapy is attractive because 1. Sildenafil
is the first pill (for oral use) with established efficacy that benefits most men
with insufficient erection; 2. compared with previous therapeutic approaches
(such as drug injections in the penis, instillations into the urinary duct,
vacuum pumps or even prostheses), Sildenafil is at least as effective, is easy to
take and appears well tolerated with no risk of a prolonged erection; 3.
remarkably, this medication stimulates erection only during sexual arousal and,
thus, has a rather "natural" effect, and 4. side effects (including headache,
facial flushing and dyspepsia or epigastric discomfort) were mostly of mild
degree and transient, so that only 4% of men interrupted treatment for this
reason. Sildenafil does not need to be taken daily, but may be taken, when
needed, 1 hour before a planned sexual activity. The new pill has the potential
to enliven the boys "wunder horn" with fresh sound.
PMID- 9658983
TI - Surgical sterilization in the United States: prevalence and characteristics, 1965
95.
AB - OBJECTIVES: This report presents national data on the prevalence of surgical
sterilization from 1965 to 1995 among women 15-44 years of age. Data are shown by
type of sterilizing operation and demographic characteristics of the women. For
the 1995 survey data, reasons for the three most common sterilizing operations
(tubal ligation, vasectomy, and hysterectomy) are shown, as well as the desire
for reversal among those with potentially reversible operations. METHODS: Data
are based on nationally representative samples of women 15-44 years of age: the
1965 National Fertility Study (NFS), and the 1973, 1982, 1988, and 1995 cycles of
the National Survey of Family Growth (NSFG). RESULTS: After rising from 16 to 42
percent between 1965 and 1988, the prevalence of surgical sterilization among
married women 15-44 years old remained stable at 41 percent in 1995. Age, parity,
religious affiliation, and education continued to be strongly associated with
overall surgical sterilization levels. Tubal ligation and vasectomy were equally
prevalent in the 1965 and 1973 surveys, but since 1962, tubal ligation has been
more prevalent than vasectomy. CONCLUSIONS: Several factors contributed to the
rise in reliance upon surgical sterilization among women 15-44 years old over the
last 3 decades: (a) aging of the post-World War II Baby Boom women (and their
partners) through the primary reproductive years; (b) relatively high
contraceptive failure rates, particularly among socioeconomically less advantaged
women; and (c) higher expectations for contraceptive effectiveness, safety, and
convenience. Overall sterilization prevalence may be leveling off among women 15
44 years old, in part due to greater delay of first and subsequent births, thus
making sterilization less of a concern while women are in this age range.
PMID- 9658984
TI - [Theophylline in treatment of bronchial obstructive diseases].
AB - The article is the review of the data from literature concerning the new role of
theophilline in the management of asthma and chronic bronchoobturative pulmonary
disease. Theophilline has been widely used to treat asthma and COPD patients
worldwide and is classified as a bronchodilatator, although there is increasing
evidence that it has antiinflammatory activity and enhances immunomodulatory
effects. The latter is therapeutically relevant to markedly lower serum
concentration (even < 10 micrograms/ml) than this required for bronchodilatation.
That is particularly clinically important because significant adverse effects
have been seen only in the case of doses greater than 10 micrograms/ml.
PMID- 9658985
TI - [Acute and critical leg ischemia].
PMID- 9658986
TI - [Comparison of anxiety in patients before surgery for varicose veins and
laparoscopic cholecystectomy].
AB - The trial of estimation of the fear degree before operation and its dependence on
the patient's sex, type of operation and anaesthesia was performed. 76 patients
before the operation were examined: group I--38 patients, including 27 women and
11 men waiting for the repair of lower extremities varicose veins under local
anaesthesia, and group II--also 38 patients, including 27 women and 11 men before
the laparoscopic cholecystectomy due to cholecystolithiasis. The Polish version
of the Spilberg's State--Trait Anxiety Inventory was used in the estimation of
the fear. The statistically significant difference of the preoperative fear
degree between examined groups was not found. There were also no significant
differences between men and women in the same group. Women in both groups
displayed a significantly higher values of the fear as a trait. Probably
laparoscopic operations are considered by the patients as more safe than
traditional ones, and maybe the trust in doctors causes the fact that the
operation under general anaesthesia is connected with low fear as well as the
operation under local anaesthesia.
PMID- 9658987
TI - [Usefulness of biochemical tumor markers (CEA, Ca 19-9, ferritin and sialic acid)
in diagnosis and prognosis of colonic neoplasms].
AB - The aim of the study was: to determine the value of CEA, Ca 19-9, ferritin and
sialic acid in diagnostics, to assess the prognostic role of serum CEA and Ca 19
9 levels before surgery and to evaluate their usefulness in diagnostics of
recurrences. The study included 352 patients with colorectal carcinoma
(adenocarcinoma). The preoperative level of CEA was elevated in 286 patients, Ca
19-9 in 108, ferritin in 60 and sialic acid in 58 patients. All of them are poor
markers in diagnostics because of the low sensitivity, respectively 47.6%, 37.0%,
16.7% and 55.2%. Preoperative high, CEA and Ca 19-9 values are associated with a
significantly poorer prognosis and with frequency of recurrences.
PMID- 9658988
TI - [Neoplasms of the large intestine in elderly patients].
AB - The aim of the study was to compare 2 groups of patients with colorectal cancer
treated between 1985-1995. The analysed group consisted of 228 patients aged over
70. Reference group consisted of 330 younger ones. The stage of colorectal cancer
(Dukes classification) was similar in both groups. Complications of the
colorectal cancer often occurred in the elderly patients (21.9% vs. 10%,
respectively). The incidence of associated diseases was also higher (70.6% vs.
59.1%). Operability was similar in both groups (93% vs. 98.8%) but resectability
was lower in the elderly group (67.4% vs. 80.1%, respectively). Postoperative
complications were observed in the similar percent of cases except those aged
over 70 (17.5% vs. 4.9%), especially after emergency operations (31.6% vs. 4.7%,
respectively).
PMID- 9658989
TI - [Levels of malonyl dialdehyde and vitamin A in blood serum after administration
of therapeutic doses of nifedipine].
PMID- 9658990
TI - [Concentration of copper and ceruloplasmin in serum of patients treated for
epilepsy].
AB - In 54 epileptic patients (28 females and 26 males) aged 21-48, serum copper (Cu)
and ceruloplasmin (Crl) concentrations were assessed. Comparing with control
group mean serum Cu and Crl concentrations were significantly increased. We
suspect that antiepileptic drugs may influence the serum Cu and Crl
concentrations by hepatic enzymes induction. Clinical picture of epilepsy and
treatment duration does not influence serum Cu and Crl concentrations.
PMID- 9658991
TI - [A proposal for management of severe acute bronchial asthma].
AB - The term acute severe asthma has recently replaced status asthmaticus to describe
severe asthma attack. Perhaps, this change was associated with better asthma
treatment, which prevents currently patients from occurrence of such a severe
exacerbation of this disease, to call it status asthmaticus. "Global Initiative
for Asthma Global strategy for asthma management and prevention" contains
rational guidance on management of this disease, but provide little information
about status asthmaticus. This fact was the main reason to prepare present
proposal, which was based on suggestion of Global Initiative for Asthma, other
current scientific papers and our own experience. We hope that this proposal will
begin further discussion, which will bring us closer to more rational solution of
this problem.
PMID- 9658992
TI - [Sleep apnea syndrome in patients with diabetes. Effectiveness of treatment for
respiratory assistance at night with continuous positive airway pressure].
AB - The group of 30 patients with OSA and diabetes type I or II has been examined.
After the first test with MESAM 4, 5 patients with considerable nocturnal
desaturation and heart rate disorders during sleep have been found. All diabetes
type II. Two polisomnographic studies (the first diagnostic polisomnography and
the second study for the settlement of treatment with CPAP) have been performed
in the patients. After 6 months of applying CPAP all the patients have been
examined again. The apnoea index was decreased (from 87.5 to 11.2) and a better
control of both systemic arterial pressure and glycaemia, saturation > 80% has
been obtained.
PMID- 9658993
TI - [Iatrogenic causes of post-traumatic reflex sympathetic dystrophy].
AB - It is suspected that some faults in the course of the treatment of traumas such
as: reduction of fractures without sufficient anaesthesia, repeated reductions,
tightness of casts, immobilization of fingers, ignoring patients' complaints of
the pain and swelling about or painful rehabilitation may have effect on the
development of the post-traumatic reflex sympathetic dystrophy. These opinions
have not been confirmed by clinical trials. The incidence of above mentioned
factors was analysed retrospectively in 165 patients with post-traumatic reflex
sympathetic dystrophy within upper extremity and in 86 patients following
fracture of distal radius without features of the condition (control group). It
was found that the patients with reflex sympathetic dystrophy significantly more
frequently complained of pain and swelling in the course of the treatment of
trauma in the cast and they were subjected more frequently to painful
rehabilitation after removing the cast. These factors appeared to have an effect
on developing the reflex sympathetic dystrophy (comparing with the control
group). The role of remaining factors that are often considered as significant in
the development of reflex sympathetic dystrophy--painful and repeated reductions
of fractures as well as immobilization of fingers-was not confirmed.
PMID- 9658994
TI - [Prostanoids in treatment of liver diseases].
AB - Knowledge related to the role of prostanoids (which include prostaglandins and
prostacycline) in controlling biological phenomena in particular organs, as well
as, in the whole human body, has increased gradually since the year 1930, up to
now. However the role of these substances in liver functions has been developed
quite recently. Experimental and clinical researches on hepatoprotective activity
of prostanoids have been carried out in the last years. Mechanism of their action
remains still unclear and can result from induction of hepatocytes regeneration,
hepatocytes membranes stabilization, improvement of hepatic microcirculation,
intracellular metabolism and respiration. In chronic liver damage it can be
related to inhibition of fibrosis. These experimental observations correlate with
amelioration of severe viral hepatic injury and improved prognosis after liver
transplantation.
PMID- 9658995
TI - [Lipoid pneumonia].
AB - The authors describe in the article etiology, histopathological features,
clinical picture and diagnostics of endogenous and exogenous lipoid pneumonia.
The advantages of broncho-alveolar fluid examination and computed tomography in
the diagnostics were emphasized.
PMID- 9658996
TI - [Chronic pleural effusion from the pancreas].
AB - Chronic, pleural effusion, characterized by a very high pancreatic enzymes
activity is a rare complication of the pancreatic diseases. It is pathognomonic
for the pancreaticopleural fistula, arising most frequently in the patients with
chronic, alcoholic pancreatitis. Clinical manifestations of the chronic pleural
effusion lead the physician's attention to the pulmonary diseases, what often is
the cause of misdiagnosis. The diagnostics of this pancreatic diseases
complication bases on the effusion's pancreatic enzymes activity evaluation and
visual methods such as computed tomography, ultrasonography, endoscopic
retrograde cholangiopancreatography. Management can be started conservatively,
but if the result is not adequate, surgical treatment is needed. As the cases of
pancreatic, chronic pleural effusion may be commoner than it is reported, author
postulates a routine evaluation of the pleural effusion alpha-amylase activity in
each case of the unclear pleural effusion.
PMID- 9658997
TI - [The significance of viral infection in asthma].
AB - The aim of the paper was to systematize, according to recent literature data, the
processes taking place in respiratory tract in the course of viral infections and
to emphasize their relevance to the development of bronchial hyperreactivity and
the pathogenesis of asthma. Furthermore, the pathophysiological mechanisms which
may be responsible for chronic infection and successively for nonspecific
bronchial hyperresponsiveness were reported. Viral pathogens which are suggested
to initiate bronchial asthma, its exacerbations and induce dyspnoea were
mentioned.
PMID- 9658998
TI - [Clinical aspects of chlamydia respiratory tract infections and their role in the
pathogenesis of asthma].
AB - Recent world-wide publications were reviewed in order to determine the clinical
characteristics and therapeutic relevance of the chlamydial respiratory tract
infections in humans. It was emphasized that Chlamydia pneumoniae could initiate
asthma and may be associated with acute asthma exacerbation. Laboratory
procedures for identifying chlamydia and difficulties concerned with the
diagnostics of this intracellular pathogen were also presented. In patients with
evidence of chlamydial infection the casual treatment (macrolides, tetracyclines,
fluoroquinolones) may induce major improvement or complete resolution of asthma.
PMID- 9658999
TI - [The ability of drivers to give first aid--testing by questionnaire].
AB - Road accidents have become a serious social problem. The scale and complexity of
this problem shows clearly that there is a necessity to improve citizens' ability
to give first aid which is especially essential in the case of drivers. Thus
special training how to give first aid at the accident place seems to be of the
primary importance. The objective of this paper is to: 1) identify to what extent
the drivers of motor vehicles are prepared to provide first aid for casualties of
the road accidents, 2) evaluate the training system of teaching motorists how to
give first aid before professional help arrives, 3) identify drivers' views on
possibilities of decreasing the number of fatal casualties of the road accidents.
The questionnaire was given to 560 employees of local government institutions in
the city of Lublin either professional or non-professional drivers. The direct
method and anonymous questionnaire were used. The results of the questionnaire
revealed clearly that very few drivers are well-prepared to give proper first aid
at the accident site. No matter what sex, education or driving experience, the
drivers have not got enough skills to give first aid and the effect is enhanced
by various psychological barriers. The questioned drivers shared the opinion that
first aid training is badly run. The drivers stressed bad quality of the training
and the fact that it is impossible to acquire practical skills that may be
required in the case of emergency. Drivers' views on possibilities of decreasing
the number of fatal casualties of the road accidents included, among others, the
following propositions: in addition to the driving licence exam first aid exam
should be compulsory severe enforcement and execution of the law which regulates
the mandatory first aid giving.
PMID- 9659000
TI - Patient participation in treatment decision making and the psychological
consequences of breast cancer surgery.
AB - Women in the early stages of breast cancer can be treated effectively with either
modified radical mastectomy or tumor excision plus postoperative radiation
therapy. Thus, breast cancer patients may be given a choice between these two
modes of treatment. In some states, physician disclosure of such treatment
alternatives for breast cancer is mandated by law. Despite the belief that
patient participation in decision making is beneficial, the evidence is
preliminary, although generally supportive. This study examined the extent to
which patient participation in the choice of surgical options was related to
psychological functioning, fear of cancer recurrence, and aspects of treatment
satisfaction 3 and 13 months postoperatively. Few associations with degree of
participation in treatment decision making or type of surgical treatment emerged
after 3 months. After 13 months, however, women with greater levels of input into
their treatment plan were more satisfied with their medical care, although they
were not better off in terms of psychological functioning or fear of cancer
recurrence. The positive effects of shared treatment decision making may be more
closely related to aspects of longer term treatment satisfaction rather than a
buffer against psychological distress resulting from breast cancer.
PMID- 9659001
TI - "What the 'caine was tellin' me to do." Crack users' risk of HIV: an exploratory
study of female inmates.
AB - This study describes factors that place crack-addicted female jail inmates at
risk for HIV infection. The study provides a portrait of the spheres of
influences that directly and indirectly promote HIV risk-taking behaviors,
women's efforts toward protecting themselves, and reported sexual behaviors. The
study documents the far-reaching effects of crack addiction. One-and-a-half-hour
interviews were conducted with 14 inmates recovering from crack addiction. The
women were aged 19 to 39, and 13 were African American. The results of this study
suggest that women's addictions are greatly shaped by their family and intimate
relationships. Addictive behavior often precluded safer sex behaviors and
increased a woman's likelihood of engagement in HIV-risky behaviors. Many women
were victims of childhood and adulthood sexual and physical victimization. Women
sought to protect themselves through sexual self-protection strategies, although
these measures were often not effective HIV risk-reduction strategies.
PMID- 9659002
TI - Behavioral and psychosocial consequences of HIV antibody counseling and testing
with African American women.
AB - This study compared a sample of low-income African American women in the
southeastern United States who had and had not yet undergone HIV counseling and
testing on risk-related cognitive mediating variables and self-reported sexual
behaviors. Four hundred sixty (N = 460) African American women were recruited
from health clinics and community settings in a southern city. Forty-five percent
of the women (n = 207) had undergone HIV counseling and testing, whereas 55% (n =
253) had never been tested. Women who were seropositive were excluded from the
analyses. After providing informed consent, the women completed a battery of
cognitive mediating measures assessing AIDS knowledge, attitudes theoretically
relevant to risk reduction, and self-reported sexual behavior. In addition, each
participant demonstrated condom application skills using a penile model. Women
who had undergone testing were younger, rated HIV disease as more serious,
considered AIDS a greater health concern, had more positive attitudes toward HIV
prevention, expressed greater intentions to use condoms, and evidenced a greater
commitment to self-protective behavior than women who were not yet tested. Women
who had undergone HIV antibody testing, however, showed no differences in sexual
behavior from women who were never tested. Sexual behavior, including numbers of
partners, frequency of unprotected intercourse, and inconsistent condom use, left
women in both groups at significant and comparable risk for HIV and sexually
transmitted disease infection. HIV counseling and testing alone may not be
effective primary prevention strategies for promoting risk reduction among
African American women.
PMID- 9659003
TI - Cervical cancer and STD health beliefs: predicting pelvic exam intentions in
undergraduates.
AB - We surveyed 119 female undergraduates to investigate if the health belief model
for both cervical cancer and sexually transmitted diseases (STDs) would predict
pelvic examination intentions. Results for cervical cancer and STDs were similar,
with barriers to obtaining an exam and perceived susceptibility contributing most
consistently to intentions. Respondents rated themselves as more susceptible to
cervical cancer than to STDs and rated STDs more serious than cancer.
Discriminant analysis found sexual activity, barriers, susceptibility to STDs,
benefits of a pelvic exam for cervical cancer, and age to reliably distinguish
women who had gotten a pelvic exam from those who had not. Contrary to previous
research, physique anxiety was a positive predictor of intentions when health
beliefs were controlled, suggesting it may represent generalized body anxiety for
some women.
PMID- 9659004
TI - Training in diagnostic ultrasound: essentials, principles and standards. Report
of a WHO Study Group.
AB - Diagnostic ultrasound is a rapidly developing imaging technology widely used in
both industrialized and developing countries. For certain diagnostic
applications, ultrasound has replaced commonly used radiographic imaging
techniques as the method of choice, and it has also made possible new areas of
diagnostic investigation. Moreover, equipment for ultrasound imaging tends to be
cheaper and more widely available than imaging equipment requiring the use of
ionizing radiation. This combination of factors has resulted in the proliferation
of diagnostic ultrasound units, and in some cases their use by individuals
without proper training, or under conditions of inadequate control. This report,
the outcome of a recent WHO Study Group, is concerned with the essentials,
principles, and standards of training for this important technology. The Study
Group has analysed problems in the effective use of diagnostic ultrasound and
reviewed current training practice worldwide. For the first time, outlines of
recommended training curricula for the general, advanced, and specialized use of
diagnostic ultrasound are presented. Recommended standards for training
programmes, training centres, and the training process are also discussed. The
report highlights the role played by professional societies, but also calls
attention to the need for appropriate legislation and regulation. The Study
Group's recommendations are relevant to all those involved in the use of
diagnostic ultrasound technology, even in countries where existing standards of
practice are high. In addition to ultrasound specialists, the report should be of
particular interest to those responsible for medical education or for formulating
policies regarding the use of health technology.
PMID- 9659005
TI - [Psychophysiologic reactions to predictable aversive stimuli in a delayed
conditioning paradigm: reinstatement of the orientating reaction or informational
control?].
AB - The preception and orienting response (OR) reinstatement hypotheses are
alternative explanations for the reduced responding to predictable as compared to
unpredictable aversive stimuli. To test differential predictions from both
theories, 60 subjects were presented with 30 stimuli varying in intensity (60
dB(A) vs 100 dB(A)) and predictability (constant vs variable warning) in a 2 x 2
between subject design. Impact ratings, SCR and heart rate were recorded as
dependent variables. According to the preception hypothesis a steep and early
decrease of responding in the predictable 100 dB(A) condition was expected,
whereas according to the OR reinstatement hypothesis a slower decrease with
differences between the predictable and unpredictable stimuli at both intensities
was hypothesized. To control for response interference only those trials were
selected for the analysis for which the interval was the same in the variable and
constant warning condition. Results revealed an intensity effect for the SCRs and
impact ratings, but no effect of predictability. Although for the heart rate
magnitude the intensity by predictability was found in favor of preception, this
result appeared to be due to differences in sensitivity between groups during the
warning interval. It was concluded that neither hypothesis proved to provide a
valid account for the reduced responding to predictable aversive stimuli, but
that the data seemed to be most consistent with a safety signal interpretation.
Time estimation was considered to be a crucial variable. It is suggested that
beyond mere signalling, additional beneficial effects of predictability can be
demonstrated in studies where procedures are used which make time estimation
unnecessary.
PMID- 9659006
TI - [Negative priming designs: comparison and improvement of measurements for
detection of cognitive inhibition].
AB - Ignoring a distractor on a prime trial generally impairs responses to that
stimulus on a subsequent probe trial. This so called negative-priming (NP) effect
supports the view that the representations of distracting stimuli underly a
cognitive inhibition during target selection (Tipper, 1985). Aiming at the
optimization of NP designs for analyzing cognitive inhibition the present paper
investigates two open questions within this context: Which classical designs
using words, letters, or pictures as stimuli are most accepted by subjects and at
the same time result in possibly strong NP effects? What is the time course of
NP, and at which interstimulus interval (ISI) the maximum is reached? In
experiment 1, three "classical" NP designs were compared within one sample of
subjects and a picture design was selected as the most suitable one. In
experiment 2 the ISI was varied within subjects; the maximal NP effect was found
at an ISI of around 1000 ms.
PMID- 9659007
TI - [Preliminary experiments on the correlation of speech errors and working memory].
AB - This article is based on the conjecture that a relation exists between the
phonological loop, part of the working memory (Baddeley, 1997), and speech
production. The influence of verbal material stored in the phonological loop on
the frequency of slips during articulation was studied experimentally. The SLIP
technique of inducing speech errors was used (Baars, 1992). Pairs of words are
presented successively to the subjects for one second each. Some of the word
pairs are to be spoken aloud. The articulation of these words can be influenced
by preceding phonologically interfering words in such a way that the probability
of exchanging the first phonemes of both words is increased (spoonerisms). In
both exploratory experiments we performed, the time interval between the
phonologically interfering information and the pairs of words which had to be
spoken aloud was systematically manipulated. According to Baddeley's theory of
working memory (1997) it was expected that phonological interference should be
restricted to a time interval of about two seconds. This expectation was
supported empirically.
PMID- 9659008
TI - Limiting models for calcification in fibrous tissues adjacent to orthopedic
implants: variational indicator functions and influences of implant stiffness.
AB - Calcification and eventual integration of orthopedic implants into bone is
important to many load-bearing devices, and the influence of load and implant
stiffness on this process are assessed in this mathematical modelling study.
Three research questions are posed in this study. First, can limiting material
models provide useful information on the overall behavior of the tissue adjacent
to a loaded orthopedic implant? Second, can the limiting models lead to
optimization criteria? Third, can an optimization approach be used to
differentiate between the four prospective remodeling rate equations which are
proposed? The answers are yes, yes, and no, respectively. A two degree of freedom
lumped parameter model for axial loading of an intramedullary implant is
considered. Two limiting composite material models are used, and the strain
energy density in the calcified and non-calcified phases are assessed as stimuli
for calcification. The rate equations posed here assume that the calcified
material volume fraction decreases at high strain-energy densities, and increases
at small strain-energy densities. In all four cases (both models, both phases)
the steady states for these rate equations find equilibrium points of indicator
functions which are a weighted sum of total strain energy and the mass of
calcified tissue in the layer considered. The weights on strain-energy density
and mass differ in each case. This shows that for appropriate choices of
parameters, all four models can yield the same results, and it also shows that an
optimization approach does not uniquely determine the appropriate rate equation
in these cases. The rate equations showed complicated dynamic behavior and a
phase-plane analysis was used which led to upper bounds on load, which depended
on implant stiffness and distal support. The predictions of the four cases
studied are compared.
PMID- 9659009
TI - Using lazy evaluation to simulate realistic-size repertoires in models of the
immune system.
AB - We describe a method of implementing efficient computer simulations of immune
systems that have a large number of unique B- and/or T-cell clones. The method
uses an implementation technique called lazy evaluation to create the illusion
that all clones are being simulated, while only actually simulating a much
smaller number of clones that can respond to the antigens in the simulation. The
method is effective because only 0.001-0.01% of clones can typically be
stimulated by an antigen, and because many simulations involve only a small
number of distinct antigens. A lazy simulation of a realistic number of clones
and 10 distinct antigens is 1000 times faster and 10,000 times smaller than a
conventional simulation--making simulations of immune systems with realistic-size
repertoires computationally tractable.
PMID- 9659010
TI - Emergence of rules in cell society: differentiation, hierarchy, and stability.
AB - A dynamic model for cell differentiation, where cells with internal chemical
reaction dynamics interact with each other and replicate was studied. It led to
spontaneous differentiation of cells and determination, as discussed in the
isologous diversification. The following features of the differentiation were
obtained: (1) hierarchical differentiation from a 'stem' cell to other cell
types, with the emergence of the interaction-dependent rules for differentiation;
(2) global stability of an ensemble of cells consisting of several cell types,
that were sustained by the emergent, autonomous control on the rate of
differentiation; (3) existence of several cell colonies with different cell-type
distributions. The results provide a novel viewpoint on the origin of a complex
cell society, while relevance to some biological problems, especially to the
hemopoietic system, is also discussed.
PMID- 9659011
TI - Evidence-based intensive care medicine.
PMID- 9659012
TI - Ethics and research in anaesthesia.
PMID- 9659013
TI - The effect of education, assessment and a standardised prescription on
postoperative pain management. The value of clinical audit in the establishment
of acute pain services.
AB - A study involving 2738 patients in 15 hospitals in the United Kingdom was
undertaken to evaluate the effect of simple methods of pain assessment and
management on postoperative pain. The study consisted of four parts: a survey of
current practice in each hospital; a programme of education for staff and
patients regarding pain and its management; the introduction of formal assessment
and recording of pain and the use of a simple algorithm to allow more flexible,
yet safe, provision of intermittent intramuscular opioid analgesia; and a repeat
survey of practice. One hospital from each of the former health regions of
England and Wales was selected for inclusion in the project. Hospitals included
representatives of different size units (university, large and small district
general hospitals). As a result of the study, there was an overall reduction in
the percentage of patients who experienced moderate to severe pain at rest from
32% to 12%. The incidence of severe pain on movement decreased from 37% to 13%
and moderate to severe pain on deep inspiration from 41% to 22%. Similar
decreases were seen in the incidence of nausea and vomiting. There was also a
slight reduction in the incidence of postoperative complications. This study
shows that simple techniques for the management of postoperative pain are
effective in reducing the incidence of pain both at rest and during movement and
should form part of any acute pain management strategy.
PMID- 9659014
TI - The effect of increasing degrees of spinal flexion on cerebrospinal fluid
pressure.
AB - The effects of increasing degrees of flexion on cerebrospinal fluid pressure were
investigated in 12 neurosurgical patients requiring lumbar subarachnoid drains.
Cerebrospinal fluid pressure and central venous pressure were measured in three
positions: fully flexed ('chin on chest'), flexed at ninety degrees and straight.
There was a significant increase in cerebrospinal fluid pressure on moving from
the fully flexed to the flexed position (p < 0.0001), but not from the flexed to
the straight position. These results were mirrored by smaller changes in central
venous pressure. In patients without intracranial pathology these increases in
cerebrospinal fluid pressure are probably unimportant. However, intracranial
pathology may result in low cerebral perfusion pressures and any increase in
cerebrospinal fluid pressure in this group may be harmful. The fully flexed
position should be avoided when inserting lumbar drains in at risk patients.
PMID- 9659015
TI - Anaesthesia and the QT interval. Effects of isoflurane and halothane in
unpremedicated children.
AB - The effects of isoflurane and halothane on the QT interval were investigated
during induction of anaesthesia. Fifty-one unpremedicated, ASA grade 1 children
were studied. Anaesthesia was induced with either isoflurane (n = 25) or
halothane (n = 26) and was maintained to the end of the study with end-tidal
concentrations of between 2.5% and 3%. Recording of the electrocardiograph, heart
rate and systolic arterial pressure were obtained at the following times: before
induction of anaesthesia; 1 min and 3 min after stable end-tidal concentrations
of anaesthetic agent had been reached; 1 min and 3 min following vecuronium
administration; at the time of tracheal intubation and 1 min and 3 min later.
Isoflurane significantly prolonged the QT interval (p < 0.001), in contrast to
halothane which shortened it (p < 0.01). Heart rate remained largely unchanged
during isoflurane anaesthesia but it decreased in the presence of halothane (p <
0.001). In both groups, systolic arterial pressure decreased significantly after
induction of anaesthesia (p < 0.001) and remained so to the end of the study. In
the isoflurane group, 12 children developed ECG repolarisation abnormalities and
in one child an arrhythmia was noticed. In the halothane group, one child
developed repolarisation changes while arrhythmias were observed in 10 children.
There were no adverse sequelae. It is concluded that halothane may be a better
anaesthetic agent than isoflurane for use in children with a prolonged QT
interval.
PMID- 9659016
TI - Anaesthetic induction time for tracheal intubation using sevoflurane or halothane
in children.
AB - The current study was designed to determine the anaesthetic induction time
required for tracheal intubation (TimeEI) with equipotent inspired concentrations
of 5% sevoflurane and 2.5% halothane in oxygen. TimeEI that prevents 50% and 95%
of patients from coughing and gross purposeful muscular movements after
intubation was defined as TimeEI50 and TimeEI95, respectively. Thirty-six
patients aged 1-7 years were enrolled in the study. Anaesthesia was induced via
mask and when TimeEI attained a predetermined value, intubation was performed
using an uncuffed tube. Each TimeEI at which tracheal intubation was attempted
was predetermined according to the up-and-down method. When intubation was
accomplished without gross purposeful muscular movements, it was considered a
smooth intubation. Determination with this method revealed that TimeEI50 and
TimeEI95 for the sevoflurane/halothane groups were 147/214 s and 194/255 s,
respectively. In conclusion, it is possible to determine TimeEI using an inspired
sevoflurane concentration of 5% and halothane 2.5% in oxygen. The technique with
5% sevoflurane seems more practical for paediatric anaesthesia induction in busy
clinical situations.
PMID- 9659018
TI - Performance characteristics of a 'to and fro' disposable soda lime canister.
AB - The performance of the Intersurgical disposable soda lime canister was compared
to British Pharmacopoeia standards for carbon dioxide absorption and to other
carbon dioxide absorber systems. This canister system more than adequately
fulfilled the equivalent of the British Pharmacopoeia standard for CO2
absorption. It performed efficiently for over 3 h of continuous use, absorbing
200 ml.min-1 at varying combinations of tidal volume and ventilation rate.
Efficiency was not dependent on close matching of tidal volume with canister
volume and there was no channelling of gases. Heat was generated by the reaction
between soda lime and CO2 and the maximum temperature recorded in the system was
42.1 degrees C. Under clinical conditions this should pose no threat of thermal
injury to the patient.
PMID- 9659017
TI - The influence of premedication on heart rate variability.
AB - Analysis of heart rate variability has been used to study the effects of
midazolam, morphine and clonidine on the autonomic nervous system, when
administered to patients for premedication. Ninety-five patients were studied 60
min before and 60 min after premedication. Normal saline (n = 25), midazolam 0.08
mg.kg-1 (n = 24), morphine 0.15 mg.kg-1 (n = 23), or clonidine 2 micrograms.kg-1
(n = 23) were administered intramuscularly by random allocation. A Holter device
was connected to the patient during the study period. Using power spectral
analysis the low-frequency and high-frequency components were calculated from the
Holter recordings. These are markers for sympathetic and parasympathetic activity
respectively; the low- to high-frequency ratio was also calculated, a ratio of >
1 signifying sympathetic dominance. A significant reduction was noticed in both
low-frequency and high-frequency power in the three premedicated groups, whereas
no changes were observed in the normal saline group. In the case of midazolam,
both the low and high frequencies were decreased but the low- to high-frequency
ratio did not change significantly. Morphine and clonidine depressed the low
frequency component more than the high-frequency component and the low- to high
frequency ratio was decreased, suggesting parasympathetic dominance. We conclude
that heart rate variability may be a useful tool for investigating the effect of
drugs on the autonomic nervous system.
PMID- 9659019
TI - Experiences and attitudes of consultant and nontraining grade anaesthetists to
continuing medical education (CME).
AB - A questionnaire survey was sent to 164 consultant anaesthetists with the aim of
investigating their experiences and attitudes to continuing medical education.
The response rate was 79%. Most anaesthetists were motivated to achieve the
required number of credits and for the majority of anaesthetists, regional,
national and internal departmental discussion meetings were the mainstay of
educational activities. The educational standard of available activities could be
improved to include more workshop-style learning opportunities and to make
journal reading a creditable continuing medical education activity. The place of
research is questioned. There was doubt as to whether sanctions such as
withdrawing recognition for training should be imposed on departments where some
anaesthetists fail to achieve the required number of credits and whether this
would motivate anaesthetists to achieve the set standards. Continuing medical
education was felt to be effective and the main barriers to attending educational
activities are discussed.
PMID- 9659020
TI - Pain on injection of propofol.
AB - Pain on injection of propofol is a common problem, the cause of which remains
unknown. The chemical properties and preparation of propofol, proposed mechanisms
for the cause of the pain and clinical strategies to prevent pain on injection of
propofol are reviewed in the hope of shedding some light on the subject.
PMID- 9659021
TI - Complications of percutaneous dilatational tracheostomy in children.
AB - Experience with percutaneous dilatational tracheostomy in children is limited.
This report discusses two significant complications which occurred following the
use of this technique.
PMID- 9659022
TI - The cuffed oropharyngeal airway as an aid to fibreoptic intubation.
AB - The cuffed oropharyngeal airway is a new disposable airway based on the Guedel
oral airway. It has an asymmetrical cuff which provides a seal as well as lifting
the base of the tongue forwards, and a 15-mm connector allowing attachment to an
anaesthetic breathing system. The device does not extend beyond the vallecula, so
that the laryngeal inlet can be visualised with a fibreoptic laryngoscope passed
between the cuff of the device and the pharyngeal wall. The advantage is that
ventilation is maintained throughout the intubating sequence. We describe its use
in a patient with oropharyngeal carcinoma.
PMID- 9659023
TI - Caesarean section following a recent retinal haemorrhage.
AB - We report a case of a 32-year-old woman who developed an antenatal Valsalva
induced retinal haemorrhage causing unilateral blindness 38 weeks into her
pregnancy. Delivery was achieved by elective Caesarean section under epidural
anaesthesia. The influence of anaesthetic technique on a recent retinal
haemorrhage is discussed.
PMID- 9659024
TI - The effects of volume and speed of injection in peribulbar anaesthesia.
AB - We have evaluated the effects of the volume and speed of administration of local
anaesthetic during peribulbar anaesthesia. One hundred and forty patients
scheduled for cataract surgery were randomly allocated to one of four groups of
35. Each patient received an injection of the same mixture of lignocaine,
bupivacaine and hyaluronidase. Patients in group A were given 9 ml at a speed of
5 ml.min-1, group B were given the same volume at 12 ml.min-1, group C were given
13.5 ml at 5 ml.min-1 and group D were given 13.5 ml at 12 ml.min-1. A
significantly higher incidence of satisfactory akinesia was found in group D,
whose pain score at injection was no higher than for the other groups. Large
volumes of local anaesthetic significantly affected intra-ocular pressure. The
incidences of early and late ptosis or diplopia were not affected by either the
rate of injection or the volume of local anaesthetic.
PMID- 9659025
TI - The use of low-dose mivacurium to facilitate insertion of the laryngeal mask
airway.
AB - Ninety patients were assigned randomly in a double-blind manner to receive 0.9%
sodium chloride, mivacurium 0.04 mg.kg-1 or mivacurium 0.08 mg.kg-1
intravenously, followed by propofol 2.5 mg.kg-1. A laryngeal mask airway (LMA)
was inserted 90 s later. The LMA was positioned correctly during the first
attempt in 87% of patients and this was not significantly altered by the use of
mivacurium. However, mivacurium decreased the incidence of swallowing, coughing,
movement and laryngospasm (p < 0.05). LMA insertion was graded as easy in 88% of
patients who had mivacurium, compared with 50% in patients who had propofol alone
(p < 0.05). The conditions during LMA insertion were similar after 0.04 or 0.08
mg.kg-1 of mivacurium. Patients were apnoeic for a mean (SD) time of 0.67 (0.72)
min after propofol alone, compared with 1.72 (1.06) min and 3.05 (1.36) min in
patients who also received mivacurium 0.04 and 0.08 mg.kg-1, respectively (p <
0.01). Patients who received mivacurium had a lower incidence of postoperative
sore throat (24-30% vs. 53%) (p < 0.05). In conclusion, low-dose mivacurium
facilitates LMA insertion and decreases the incidence of postoperative sore
throat.
PMID- 9659026
TI - Comparison of pain from insertion of venous cannulae; a volunteer study.
AB - The pain from insertion of two small cannulae was compared in 26 volunteers. Each
subject was blindfolded and had both a 22 G and a 20 G cannula inserted in random
order. One subject was rejected as cannulation was unsuccessful. Of the remaining
25 subjects, 12 found the 22 G more painful and 13 the 20 G. This difference was
not significant (chi squared p > 0.1).
PMID- 9659027
TI - Exogenous adenosine potentiates hypnosis induced by intravenous anaesthetics.
AB - We investigated the effect of adenosine on hypnosis induced by thiopentone,
propofol and midazolam in mice. The onset and duration of hypnosis were
determined by the loss of righting reflex. Adenosine and 2-chloroadenosine caused
a significant shortening of onset of sleep-time and prolongation of duration of
sleep-time in all groups (p < 0.05). Dipyridamole administration before combined
intravenous anaesthetic-adenosine or intravenous anaesthetic-2-chloroadenosine
administration produced similar effects to adenosine (p < 0.05). The adenosine
antagonist theophylline, given before intravenous anaesthetic-adenosine or
intravenous anaesthetic-2-chloroadenosine administration caused a significant
delay in onset of sleep-time and shortening in the duration of sleep-time (p <
0.05). We conclude that central excitatory noradrenergic neurones play an
important role in adenosine, 2-chloroadenosine and dipyridamole-induced hypnotic
responses to intravenous anaesthetics and their inhibition by adenosine
antagonists.
PMID- 9659028
TI - The effect of mivacurium pretreatment on intra-ocular pressure changes induced by
suxamethonium.
AB - Forty patients without eye disease, undergoing elective nonophthalmic surgery,
were studied in a double-blind, randomised, placebo-controlled study evaluating
the efficacy of mivacurium pretreatment in attenuating the rise in intra-ocular
pressure in response to suxamethonium administration, laryngoscopy and
intubation. The patients were randomly allocated to receive either mivacurium
0.02 mg.kg-1 or normal saline as pretreatment 3 min before a rapid sequence
induction technique using alfentanil, propofol and suxamethonium. Suxamethonium
induced a significant increase in intra-ocular pressure in the control group but
not in the mivacurium pretreatment group (mean (SEM) increase = 3.5 (1.2) mmHg
vs. 0.4 (0.8) mmHg, p < 0.05). There was a decrease in intra-ocular pressure in
both groups after laryngoscopy and intubation with no significant difference
between the two groups. These results show that mivacurium pretreatment is
effective in preventing the increase in intra-ocular pressure after suxamethonium
administration.
PMID- 9659029
TI - The efficacy of ginger root in the prevention of postoperative nausea and
vomiting after outpatient gynaecological laparoscopy.
AB - To determine the anti-emetic effect of ginger as compared to droperidol, 120
patients scheduled to have gynaecological diagnostic laparoscopy as day cases
were randomly allocated into placebo, droperidol, ginger and ginger plus
droperidol groups to receive either 2 g of ginger or 1.25 mg of droperidol or
both. There were no significant differences in the incidences of postoperative
nausea which were 32%, 20%, 22% and 33%, and vomiting which were 35%, 15%, 25%
and 25% in the four groups, respectively. We conclude that ginger powder, in the
dose of 2 g, droperidol 1.25 mg or both are ineffective in reducing the incidence
of postoperative nausea and vomiting after day case gynaecological laparoscopy.
PMID- 9659030
TI - Ephedrine/Epinephrine drug label confusion.
PMID- 9659031
TI - Thoracic epidural analgesia and coronary artery bypass graft surgery.
PMID- 9659032
TI - Thoracic epidural analgesia and coronary artery bypass graft surgery.
PMID- 9659033
TI - A simple approach to dosing in children.
PMID- 9659034
TI - Asthma: a plea for commonsense.
PMID- 9659035
TI - Ilioinguinal nerve block for orchidopexy.
PMID- 9659036
TI - Self-administration of pre-operative analgesic suppositories.
PMID- 9659037
TI - Sevoflurane and adult acute epiglottitis.
PMID- 9659038
TI - Warning notice above beds.
PMID- 9659039
TI - Old habits, the circle system and short procedures.
PMID- 9659040
TI - High-frequency ventilation for management of respiratory complications after
trauma and major orthopaedic surgery.
PMID- 9659041
TI - Management of traumatised patients in the ICU.
PMID- 9659042
TI - Portable cardiopulmonary support (ECPS) in the emergency room.
PMID- 9659043
TI - Transoesophageal echocardiography and volume management in the intensive care
unit.
PMID- 9659044
TI - The stress response and its modification by regional anaesthesia.
PMID- 9659045
TI - Haemodynamic changes during surgery in the knee-elbow position: a
transoesophageal echo-Doppler study.
PMID- 9659046
TI - The use of ropivacaine in brachial plexus anaesthesia.
PMID- 9659047
TI - Sciatic nerve blocks: approaches, techniques, local anaesthetics and
manipulations.
PMID- 9659048
TI - Anaesthetic techniques for knee arthroscopy.
PMID- 9659049
TI - Continuous brachial plexus blockade via the vertical infraclavicular approach.
PMID- 9659051
TI - Regional anaesthesia for low back operations.
PMID- 9659050
TI - Interscalene brachial plexus block combined with total intravenous anaesthesia
and laryngeal mask airway for shoulder surgery.
PMID- 9659052
TI - Spinal anaesthesia: hearing loss, failure, transient radicular irritation (TRI).
PMID- 9659053
TI - Blood substitutes: is it time for work process redesign in transfusion medicine?
PMID- 9659054
TI - Predeposit, intentional peri-operative haemodilution and erythropoietin level in
major orthopaedic surgery.
PMID- 9659055
TI - Autotransfusion: role of perioperative blood salvage and predeposit.
PMID- 9659056
TI - Blood saving in children.
PMID- 9659057
TI - New developments in autologous transfusion systems.
PMID- 9659058
TI - Pathophysiology and management of the fat embolism syndrome.
PMID- 9659059
TI - The peri-operative management of major orthopaedic procedures.
PMID- 9659061
TI - Practicability and safety of intra-operative autotransfusion with irradiated
blood.
PMID- 9659060
TI - Spinal cord monitoring.
PMID- 9659062
TI - Heat loss during major orthopaedic surgery.
PMID- 9659064
TI - Organisation and methods in postoperative pain therapy.
PMID- 9659063
TI - Hypothermia prevention and treatment.
PMID- 9659065
TI - Spinal sufentanil.
PMID- 9659066
TI - Postoperative pain management in day surgery.
PMID- 9659067
TI - Antithrombin (AT) substitution: sense or nonsense?
PMID- 9659068
TI - Coagulation support: fresh frozen plasma versus clotting factor concentrate.
PMID- 9659069
TI - Thromboembolic complications and pharmacological prophylaxis in orthopaedic
surgery.
AB - Two thousand, three hundred and three patients who had undergone major
orthopaedic surgery were statistically analysed for the incidence of
complications comparing three regimens of prophylaxis and coexisting diseases;
2090 patients did not present postoperative complications. PTE occurred in 0.65%
(one fatal). The mortality rate was 0.34% and the incidence of haemorrhage
(haematoma and one gastric haemorrhage) was 3.8%. Patients treated with indobufen
had a shorter hospital stay and the need for homologous blood transfusions was
lower than for patients treated with calcium heparin. The rate of PTE was notably
different in the three groups, being lower in the group treated with enoxaparin,
although this result was not found to be statistically significant.
PMID- 9659070
TI - Interactions between epidural analgesia and antifibrinolytics.
PMID- 9659071
TI - Point-of-care coagulation monitoring: applications of the thromboelastography.
PMID- 9659072
TI - Consensus use of desmopressin and antifibrinolytics in three university clinics.
PMID- 9659073
TI - Acute peripheral ischaemia and compartment syndromes: a role for hyperbaric
oxygenation.
PMID- 9659074
TI - Severe trauma and infections.
PMID- 9659075
TI - Hyperbaric oxygen therapy in osteomyelitis.
PMID- 9659077
TI - Loco-regional anaesthesia and trauma in children: what can we do in the emergency
room?
PMID- 9659076
TI - Principles in peri-operative paediatric medicine.
PMID- 9659078
TI - Ropivacaine for central blocks in children.
PMID- 9659079
TI - Stress response in orthopaedics and trauma in paediatrics: general versus
regional anaesthesia.
PMID- 9659080
TI - Anaesthesia in handicapped children.
PMID- 9659081
TI - Echocardiography on the neonatal unit: a job for the neonatologist or the
cardiologist?
PMID- 9659082
TI - Licensing of medicines.
PMID- 9659083
TI - Epidemiology of head injury.
PMID- 9659084
TI - Evidence-based dilemmas in pre-school vision screening.
PMID- 9659085
TI - A prospective 10 year follow up study of patients with neurofibromatosis type 1.
AB - OBJECTIVE: To establish the prevalence and incidence of symptoms and
complications in children with neurofibromatosis type 1 (NF1) and to assess
possible risk factors for the development of complications. DESIGN: A 10 year
prospective multidisciplinary follow up study. PATIENTS: One hundred and fifty
children diagnosed with NF1 according to criteria set by the National Institutes
of Health. RESULTS: In 62 of 150 children (41.3%) complications were present,
including 42 (28.0%) children with one complication, 18 (12.0%) with two
complications, and two (1.3%) with three complications (mean (SD) duration of
follow up 4.9 (3.8) years). Ninety five of the 150 children presented without
complications (follow up, 340.8 person-years). The incidence of complications was
2.4/100 person-years in this group. An association was found between behavioural
problems and the presence of complications. CONCLUSION: This is the largest
single centre case series of NF1 affected children followed until 18 years of
age. Children with NF1, including those initially presenting without
complications, should have regular clinical examinations.
PMID- 9659086
TI - Sleep and psychological disturbance in nocturnal asthma.
AB - Subjective and objective sleep disturbance was studied in children with nocturnal
asthma. Relations between such disturbance and daytime psychological function
were also explored, including possible changes in learning and behaviour
associated with improvements in nocturnal asthma and sleep. Assessments included
home polysomnography, parental questionnaires concerning sleep disturbance,
behaviour, and mood and cognitive testing. Compared with matched controls,
children with asthma had significantly more disturbed sleep, tended to have more
psychological problems, and they performed less well on some tests of memory and
concentration. In general, improvement of nocturnal asthma symptoms by changes in
treatment was followed by improvement in sleep and psychological function in
subsequent weeks. The effects of asthma on sleep and the possible psychological
consequences are important aspects of overall care.
PMID- 9659087
TI - Iron status of Asian children aged 2 years living in England.
AB - Haemoglobin and ferritin values were analysed in blood from 1057 children, aged 2
years, of Asian parents living in England. Children who had thalassaemia trait or
a current/recent infection were excluded. Twenty nine per cent of Pakistani, 25%
of Bangladeshi, and 20% of Indian children had haemoglobin < 110.0 g/l. The
recent national diet and nutrition survey of preschool children found a
prevalence of 12% of 2 year olds with haemoglobin < 110.0 g/l. No single factor
accounted for more than a small proportion of the variance in haemoglobin and
ferritin values, but the most significant factors that had a negative effect on
iron status included the amount of cows' milk consumed, the use of a baby bottle,
and mother's place of birth being outside of the UK. Taking vitamin or iron
supplements was positively associated with iron status in one or more of the
three groups.
PMID- 9659088
TI - Health at age 11: reports from schoolchildren and their parents.
AB - OBJECTIVE: To present self reports by children and reports by parents on behalf
of their children relating to general health, current conditions, and recent
symptoms. DESIGN: Questionnaires completed by children and parents as part of the
longitudinal "West of Scotland 11 to 16 study: teenage health." SETTING: 135
primary schools in Central Clydeside. SUBJECTS: 2586 children aged 11 years,
surveyed from October 1994 to March 1995 (response rate 93%). Questionnaires also
completed by parents of 86% of the sample. MAIN OUTCOME MEASURES: Ratings of
health over the past 12 months, presence of (limiting) longstanding illness, nine
current conditions, and 11 recent symptoms. RESULTS: Only 47% of children
described their health as "good" in the previous year. Around 20% reported a
longstanding illness and 8% a limiting illness; 20% reported migraine or
headaches, 13% reported asthma. Recent stomach aches or sickness, colds or flu,
and headaches were each reported by around 60%. "Malaise" (emotional) symptoms
were common. Parents reported similar levels of (limiting) longstanding illness,
but rates of conditions and symptoms reported by parents were lower than reported
by their children. Parent-child agreement was greatest for the presence of
longstanding illness and the conditions of asthma, diabetes, and skin problems.
It was lower for recent symptoms, particularly those categorised as reflecting
malaise. CONCLUSIONS: These results challenge assumptions of good health and
wellbeing at this age. Illness reporting depends on various factors, including
saliency, social desirability, and definitions of normality. Parent-child
discrepancies may reflect different definitions of illness or symptoms; they do
not mean that one should be dismissed as "wrong."
PMID- 9659089
TI - Mortality and diabetes from a population based register in Yorkshire 1978-93.
AB - OBJECTIVE: To investigate mortality of children diagnosed with insulin dependent
diabetes mellitus (IDDM) and to identify common factors before death. DESIGN:
Follow up of a population based cohort of children diagnosed with IDDM to
ascertain deaths. SETTING: Children were diagnosed in Yorkshire but followed up
throughout the United Kingdom. SUBJECTS: From the Yorkshire Children's Diabetes
Register details of 1854 children aged 0-16 years (1978-93) were submitted to the
NHS Central Register. MAIN OUTCOME MEASURE: Notification and causes of death.
RESULTS: 98.3% of cases were traced and 26 deaths identified. Follow up ranged
from 1-18 years (median 9.3 years), providing 17,350 person-years of IDDM.
Fifteen deaths (58%) were attributed to diabetes or its complications; 11 (42%)
were unrelated and included one suicide. For mortality from all causes, the
standardised mortality ratio (SMR) of 247 (95% confidence interval (CI) 163 to
362) was significantly increased for those under 34 years. The largest number of
deaths (n = 10) occurred in the 15-19 year age range, with an SMR of 442 (95% CI
209 to 802). Case note examination showed a clear tendency towards poor diabetic
control, and worries over control were expressed before death by health care
professionals. CONCLUSIONS: Despite advances in treatment, IDDM still carries an
increased mortality for young people, particularly in the "transition" age range.
PMID- 9659090
TI - Social adversities and anxiety disorders in the Gaza Strip.
AB - AIM: To investigate the rate and nature of anxiety symptoms and disorders in
children, and their relation to social adversities in a cultural sample not
previously researched. METHODS: 237 children aged 9 to 13 years living in the
Gaza Strip were selected randomly from 112 schools. Children completed the
revised manifest anxiety scale (a questionnaire with yes/no answers for 28
anxiety items and nine lie items), and teachers completed the Rutter scale (a
questionnaire of 26 items of child mental health problems rated on a scale of 0
2: "certainly applies", "applies somewhat", "doesn't apply"). RESULTS: Children
reported high rates of significant anxiety problems (21.5%) and teachers reported
high rates of mental health problems in the children (43.4%) that would justify
clinical assessment. Anxiety problems, particularly negative cognitions,
increased with age and were significantly higher among girls. Low socioeconomic
status (father unemployed or unskilled worker) was the strongest predictor of
general mental health problems. Living in inner city areas or camps, both common
among refugees, was strongly associated with anxiety problems. CONCLUSIONS: The
rate and nature of anxiety disorders were similar to those established in Western
societies. Factors reflecting social adversity and lack of stability were also
similarly involved. There may be more similarities in the presentation of mental
health symptoms across cultures than previously believed.
PMID- 9659091
TI - Relation between dietary intake and nutritional status in cystic fibrosis.
AB - This study evaluated adherence to current dietary recommendations of children
with cystic fibrosis and mild lung disease and their siblings by comparing energy
intake. Fifty children (25 with cystic fibrosis) aged between 7 and 12 years
completed the study. Energy intake was assessed by weighed dietary intake,
resting energy expenditure was used to calculate recommended daily intakes. The
children with cystic fibrosis had significant deficits in Z scores for both
height and weight compared with their siblings, but there was no difference in
percentage of ideal weight for height. The cystic fibrosis group had a
significantly higher energy intake per kilogram body weight per day but there was
no difference in the percentage of energy derived from fat, protein or
carbohydrate. Energy intake (per kg/day) and fat intake (g/kg) were both
significant predictors of weight for height in the cystic fibrosis group. Targets
for dietary management in cystic fibrosis should perhaps be related to fat intake
per kilogram body weight.
PMID- 9659092
TI - Serum eosinophilic cationic protein may predict clinical course of wheezing in
young children.
AB - Thirty eight children aged between 2 and 4 years with three or more episodes of
wheezing were studied to evaluate the role of eosinophil inflammation and its
relation to persistence of wheezing two years later. Serum eosinophilic cationic
protein, total eosinophil count, total IgE, skin prick test, and clinical
features were evaluated at visit 1. Two years later at a second clinical
evaluation the children were separated into two groups: group 1, those with
persistent wheezing (n = 20); group 2, those who had been asymptomatic over the
past six months (transient wheezing) (n = 18). Mean (SEM) eosinophilic cationic
protein at visit 1 was higher in group 1 than in group 2 (29.63 (5.16) v 14.42
(2.77) micrograms/l), and the probability of continuing wheezing at age 5 years
was greater in children with values > or = 20 micrograms/l at visit 1 than in
those with lower values (relative risk = 2.88, 95% confidence interval 1.42 to
5.87, p < 0.001). Eosinophil inflammation is present from the beginning of the
disease in the children who are going to continue with wheezing at age 5 years.
The measurement of serum eosinophilic cationic protein may help in evaluating
which wheezing infants are going to continue with asthma in the future.
PMID- 9659093
TI - Randomised controlled trial of sucrose by mouth for the relief of infant crying
after immunisation.
AB - OBJECTIVES: To evaluate the effect of sucrose solution given by mouth on infant
crying times and measures of distress in the immunisation clinic. DESIGN:
Randomised, double blind, placebo controlled trial of sucrose solution 75% wt/vol
v sterile water as a control. SETTING: The immunisation clinic of the Women's and
Children's Hospital, Adelaide. PATIENTS: A total of 107 healthy infants attending
for 2, 4, or 6 month immunisations with polio by mouth (Sabin), intramuscular
diphtheria, tetanus, and pertussis (DTP), and intramuscular Haemophilus
influenzae type b were randomised to receive 2 ml 75% sucrose solution or sterile
water by mouth before the two injections. METHODS: The duration of infant crying
was recorded during and immediately after two intramuscular immunisations and
infant distress was assessed by a visual analogue scale (Oucher scores)
independently by a nurse and a parent. RESULTS: The administration of 2 ml 75%
sucrose solution by mouth reduced the infant crying time and Oucher distress
scores after immunisation with DTP/H influenzae type b. CONCLUSIONS: Infant
immunisation by intramuscular injection is a distressing procedure for infants
and parents. Sucrose solution at a high concentration reduces infant distress and
is safe and clinically useful in this setting.
PMID- 9659094
TI - Use of pulse oximetry for blood pressure measurement after cardiac surgery.
AB - Blood pressure measurement using pulse oximeter waveform change was compared with
an oscillometric measurement and the gold standard, intra-arterial measurement,
in children after cardiac surgery. Forty six patients were enrolled and divided
into groups according to weight. Simultaneous blood pressure measurements were
obtained from the arterial catheter, the oscillometric device, and the pulse
oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff
proximal to the oximeter probe. The blood pressure measurements from the pulse
oximeter method correlated better with intra-arterial measurements than those
from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences
between the pulse oximeter and intra-arterial measurements were significantly
smaller than between the oscillometric and intra-arterial measurements in
children less than 15.0 kg. The pulse oximeter waveform change is an accurate and
reliable way to measure blood pressure in children non-invasively, and is
superior to the oscillometric method for small patients.
PMID- 9659095
TI - Reference values for pulse oximetry at high altitude.
AB - OBJECTIVE: To determine reference values for oxygen saturation (Sao2) in healthy
children younger than 5 years living at high altitude. DESIGN: One hundred and
sixty eight children were examined for Sao2 at 4018 m during well child visits.
Physiological state was also noted during the examination. RESULTS: The mean Sao2
was 87.3% (95% confidence intervals (CI) 86.7%, 87.9%) with a median value of
87.7%. A significant difference was observed in Sao2 between children younger
than 1 year compared with older children, although the difference was no longer
demonstrable when sleeping children were excluded. CONCLUSIONS: This study has
provided a reference range of Sao2 values for healthy children under 5 years old
so that pulse oximetry may be used as an adjunct in diagnosing acute respiratory
infections. Younger children were also shown to have a lower mean Sao2 than older
children living at high altitude, which suggests physiological adaptation to high
altitude over time. In addition, sleep had a lowering effect on Sao2, although
the clinical importance of this remains undetermined.
PMID- 9659096
TI - Chromosome aberrations in coeliac and non-coeliac enteropathies.
AB - The frequency of chromosomal aberrations in peripheral blood lymphocytes was
assessed in three groups of children: untreated coeliac disease (n = 20); non
coeliac disease enteropathies (n = 15); controls (n = 15). The mean frequency of
aberrant cells and the total number of aberrations per 100 metaphases was
increased in the coeliac disease group compared with controls by factors of 5 and
6, respectively (p < 0.01 for both). Aberrant cells and total aberrations were
similarly increased in the non-coeliac disease enteropathy group by a factor of
3.7 in each case (p < 0.05). However, the frequency of aberrations in the two
enteropathy groups was not significantly different. Children with coeliac
disease, similar to affected adults, have evidence of increased chromosomal
instability. However, similarly increased chromosomal aberrations are seen in
children with non-coeliac disease enteropathies, indicating that the abnormality
is not specific for coeliac disease.
PMID- 9659097
TI - Growth hormone replacement in patients with Langerhan's cell histiocytosis.
AB - OBJECTIVES: To assess the impact of growth hormone on growth and the underlying
disease in children with growth hormone deficiency as a result of Langerhan's
cell histiocytosis. STUDY DESIGN: Retrospective analysis of data from the Kabi
(Pharmacia & Upjohn) international growth database (KIGS) for 82 children with
Langerhan's cell histiocytosis treated with recombinant growth hormone. RESULTS:
At the start of treatment the median (10-90th centile) age was 9.0 (5.2 to 14.7)
years, with a median height standard deviation score (SDS) of -2.0 (-3.5 to
0.9). The median pretreatment height velocity (measured in cm/year) was 3.6 (0.9
to 6.4); this increased to 8.8 (3.8 to 12.0) in the first year of treatment with
growth hormone, and then remained significantly greater than the pretreatment
height velocity at 7.3 (4.4 to 9.7) and 7.1 (4.1 to 9.3) cm/year in the second
and third years, respectively. The median height SDS increased from -2.0 to -0.8
(-2.3 to 0.6) by the end of three years of treatment. There was no increase in
the recurrence rate of the underlying disease and no adverse event could be
directly attributed to growth hormone treatment, apart from one case of benign
intracranial hypertension that resolved on stopping treatment with growth
hormone. CONCLUSIONS: Growth hormone replacement treatment for patients with
Langerhan's cell histiocytosis with growth hormone deficiency is beneficial and
safe.
PMID- 9659099
TI - Socioeconomic status and changes in body mass from 3 to 5 years.
AB - The influence of social status on the development of body mass was analysed in a
retrospective cohort study of 675 Belgian children monitored between the ages of
3 and 5 years by the preventive medical services in Brussels. At age 3, no
association between excess weight and social status was observed. Adiposity
rebound before age 5 was inversely related to body mass at age 3 and was
independent of social status. The social influences on obesity observed in
adolescence cannot be explained by a higher frequency of early adiposity rebound
in children of low socioeconomic status.
PMID- 9659098
TI - Effect of growth hormone on height, weight, and body composition in Prader-Willi
syndrome.
AB - AIMS: To evaluate the effect of the administration of growth hormone on stature,
body weight, and body composition in children aged between 4 and 10 years with
Prader-Willi syndrome. METHODS: Height, weight, and skinfold thickness were
recorded in 25 children using standard anthropometric techniques at recruitment,
and six months later, shortly before the start of daily subcutaneous injections
of growth hormone. Body composition was assessed via a measurement of total body
water using stable isotopes. Measurements were repeated at the end of the six
months of growth hormone administration. Measurements of height, weight, and
skinfold thickness were expressed as standard deviation scores (SDSs). RESULTS:
There was a significant reduction in the percentage of body fat after growth
hormone treatment; height velocity doubled during treatment; body weight did not
change significantly when expressed as an SDS. Skinfold thickness at both the
triceps and subscapular site decreased in absolute terms and when expressed as an
SDS. CONCLUSIONS: These results indicate sufficient potential benefit to justify
a more prolonged trial of growth hormone treatment and an exploration of
different dosage regimens in children with Prader-Willi syndrome.
PMID- 9659100
TI - Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr
virus infection.
AB - Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome
with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV)
infections are described. One patient had primary HHV-7 infection and reactivated
EBV infection. The other had primary HHV-7 and EBV infections. These cases
indicated that HHV-7 is capable of inducing infectious mononucleosis-like
illness. Multiple herpesvirus infection in one of the patients also suggests that
interaction among herpesviruses can occur in vivo. The consequence of this
interaction may have clinical implications.
PMID- 9659101
TI - Neurocardiogenic syncope: a model for SIDS.
AB - A 5 1/2 month old male infant who had suffered three acute life threatening
episodes was admitted for overnight sleep studies but was found dead after their
completion while still in hospital. A necropsy classified the cause of death as
sudden infant death syndrome (SIDS). The sleep studies had shown no periods of
apnoea (> 20 seconds) or bradycardia (< 90 beats/min), and a rapid response to
nasal occlusion (5 seconds). However, autonomic function during sleep was poor,
with reduced heart rate variability (6 beats/min v control 24 beats/min, SD 6.2)
and postural hypotension (a 12-14% fall in resting systolic blood pressure)
associated with a fall in heart rate when tilted to a vertical position. Postural
hypotension with bradycardia occurs in adults with unexplained syncopal episodes
and is called a neurocardiac reflex. It involves poor vasomotor tone with
peripheral pooling of blood, a consequent reduction in central venous return and
cardiac distension, and in some individuals a neurally mediated bradycardia, as
seen in this infant, rather than the expected tachycardia. A progressive
bradycardia is the predominant mechanism of death seen in SIDS infants dying on
cardiorespiratory monitors at home. This case suggests that a neurocardiac reflex
occurs in infants, may have been involved in this infant's death, and deserves
further study in the context of SIDS.
PMID- 9659102
TI - Teaching paediatrics for the developing world.
PMID- 9659104
TI - Masculinism disguised as feminism.
PMID- 9659103
TI - Molecular biology and genetics of allergy and asthma.
PMID- 9659105
TI - Implementing a children's day assessment unit in a district general hospital.
PMID- 9659107
TI - Sedation for invasive procedures in paediatrics.
PMID- 9659106
TI - How often should we screen for hypothyroidism in girl's with Turner's syndrome?
PMID- 9659108
TI - PLink, plastic surgery and the Internet.
AB - The Internet is a fast growing, global computer network that is easy to access at
a low cost. This form of communication allows rapid electronic exchange of
information such as text, pictures, animations, video and sound. This offers
physicians an opportunity to enhance the quality of patient care, research and
communication with colleagues. Patients who previously had limited access to
information concerning diseases and treatment options are now able to find
medical information on the Internet. The quality of information found on the
Internet varies widely, from the most up-to-date protocols, produced by leading
physicians and surgeons, to out of date or inaccurate recommendations. Faced with
an enormous quantity of information of variable quality, guidelines certified by
recognised medical organisations are essential to provide websites with valuable
information. This so-called "safe house principle" creates reliable places on the
Internet ("safe houses") that are generally accepted and trusted for containing
valid information. We have created such a "safe house" on plastic surgical topics
for the Netherlands Society for Plastic Surgery called "PLink" (the Plastic
Surgery link). Its goals are: 1. to provide a well-organised list of existing
plastic surgery Internet resources; 2. to improve communication; and 3. to
provide original information on plastic surgical subjects for patients and
physicians. Professionals always review the content. Since July 1996 our files
have been accessed over 1.3 million times in 17 months, with the visit rate
increasing from 1470 in July 1996 to 4200 in March 1997 and remaining stable
since then. This indicates that there is a growing need for high quality
information on plastic surgery on the Internet.
PMID- 9659109
TI - Endoscopically assisted tissue expander insertion using balloon dissection.
AB - A method of tissue expander insertion using balloon dissection and endoscopy is
presented. In tissue expander operations, accuracy and atraumatic techniques are
important for preventing complications, and the endoscopic balloon provides safer
and faster dissection of the fascial plane than can be achieved with endoscopic
scissors, allowing the creation of subcutaneous pockets for tissue expander
placement. The balloon can separate loose areolar tissue between deep and
superficial fascia, forming a fascial cleft. The procedure has been used in 10
cases with satisfactory results.
PMID- 9659110
TI - The distally based lateral adipofascial flap.
AB - The distally based lateral adipofascial flap can be based either on the lowermost
perforator or the anterior perforating branch of the peroneal artery avoiding
sacrifice of the main peroneal artery. It has been used successfully to resurface
soft tissue defects either on the lateral or medial aspect of the lower third of
the leg in 13 cases. The size of these flaps varied from 2.0 cm x 5.0 cm to 4.5
cm x 15.0 cm in size. These cases had minimal donor site morbidity and had
positive aesthetic results. The advantages were: 1. Choice of either the
lowermost perforator or the anterior perforating branch giving a wide arc of
rotation; 2. Preservation of the superficial peroneal nerve; 3. Primary closure
of the donor site.
PMID- 9659111
TI - Expansion of the oral end of free revascularised jejunum with a jejunal patch
flap rotated like a folding fan.
AB - We have devised a new expansion process for the reconstruction of the cervical
oesophagus with free revascularised jejunum in cases of hypopharyngeal cancer.
The jejunal island flap is divided into three subislands and the major island of
the caudal end is split partially at its oral end. The middle island is split,
trimmed triangularly, and inserted into opened major island to expand the
diameter of the oral end of the conduit for the cervical oesophagus and to make
it funnel-shaped. The smallest island on the oral side is used as a circulation
monitor for the transferred jejunum. Because the jejunal island patch is rotated
around the root of mesentery like a folding fan and joined to the major island,
there is neither shortening of the pedicle nor distortion. This method allows
expansion of the oral end by up to 180% to facilitate end to end anastomosis in
proximal pharyngeal defects.
PMID- 9659112
TI - Application of reduction mammaplasty in treatment of giant breast tumour.
AB - Reduction mammaplasty has been the traditional method for managing breast
hypertrophy or severe ptosis in the field of plastic surgery. We describe two
patients with giant breast hamartomas treated with the application of reduction
mammaplasty by either the superior or inferior pedicle technique. Both had
satisfactory results with symmetry of breast projection and nipple-areola complex
placement. Standard plastic surgical techniques may be effectively applied in the
treatment of giant breast tumours which compromise the aesthetic appearance of
the breast.
PMID- 9659113
TI - The lateral thigh V-Y flap for the repair of ischial defects.
AB - The lateral thigh fasciocutaneous flap described by Maruyama et al in 1984 is a
useful method for the repair of ischial and trochanteric defects. We clinically
re-evaluated the potential vascular territory of the nutrient artery for this
flap, i.e., the first profunda perforator, and have newly designed the postero
lateral thigh V-Y flap in the area including the proximal two-thirds of the
posterior thigh. This flap was applied to five difficult or recurrent ischial
defects, and satisfactory results were obtained in all cases. For the
reconstruction of ischial defects, the postero-lateral thigh V-Y flap has the
following advantages; the proximal and well-vascularised portion of the flap is
inserted into the area of the previously excised pressure sore, and this flap can
potentially be readvanced if a recurrent pressure sore should develop. A Z-plasty
can be performed to prevent excessive tension on the skin closure at the junction
of the V-Y advancement flap. The postero-lateral thigh V-Y flap can be considered
one of the first-line options for both primary and recurrent ischial pressure
sores.
PMID- 9659114
TI - Evaluation of new improved solution containing trehalose in free skin flap
storage.
AB - BACKGROUND DATA: In this study, we evaluated a new intracellular type (IT-K)
solution containing trehalose in a rabbit free skin flap storage model. Trehalose
is a nonreducing disaccharide that can stabilise cell membranes under various
stressful conditions. MATERIAL AND METHOD: Seventy-two free skin flaps of the ear
of rabbits were preserved in Euro-Collins (EC) solution or in IT-K solution for
24, 48, and 72 h at 4 degrees C. After completion of preservation, these flaps
were replanted to the other ear by microsurgical techniques. Viability study and
photo documentation were performed daily for 7 days. Tissue specimens were taken
24 h after vascular anastomosis, fixed in 10% formaldehyde and stained with
haematoxylin and eosin (HE). Survival rates were analysed by Fisher's exact test
for comparison of the two experimental groups. Values of P < 0.05 were considered
to be statistically significant. RESULTS: After 7 days, a survival rate of 100%
of flaps were observed in both solutions after 24 h of preservation. After
preservation for 48 h in IT-K solution the survival rate was 100%. However, in EC
solution survival decreased to 75% (9 of 12 preserved flaps survived). This
difference increased to 33.3% (4 of 12 flaps) in EC solution and 91.6% (11 of 12
flaps) (P < 0.01) in IT-K solution when the flaps were stored for 72 h. Light
microscopic examination also showed less damage in flaps preserved in IT-K
solution than in these preserved in EC solution. CONCLUSION: IT-K solution was
superior to EC solution in the preservation of free skin flaps on rabbit ears
when stored for 48 and 72 h.
PMID- 9659115
TI - An inexpensive self fabricated pressure clip for the ear lobe.
AB - Pressure therapy is an integral part of keloid treatment. There are certain areas
of the body which are prone to keloid formation but are not amenable to pressure
therapy. The ear lobe is one such area. A simple, self fabricated and inexpensive
pressure clip has been used for applying postoperative pressure to the ear lobe.
This is fabricated with cold-cure poly methyl methacrylate and orthodontic wire.
This has been used in 41 ear lobe keloids in 26 patients along with
postexcisional triamcinolone acetonide therapy, 5 ear lobe reconstructions and 2
cases of ear lobe clefts over a period of 8 years. Although these clips are not
very aesthetic, still the acceptability is very high as the patients were well
motivated. A total of 27 ear lobes in 18 patients of ear lobe keloids have
undergone ear boring after 6-18 months of pressure therapy. The only complication
noticed is in the form of pressure ulcer due to continuous pressure in two
patients at the beginning of our experience with these clips. These healed well
after temporarily stopping the use of the clip.
PMID- 9659116
TI - 'Tusked' forceps for rapid and atraumatic subcuticular closure of the skin.
AB - A modified skin forceps is presented that combines the advantages of skin hook
and dressing forceps. Its use facilitates the atraumatic placement of continuous
intradermal sutures by the surgeon who is working unassisted.
PMID- 9659117
TI - Thumb reconstruction, after Marjolin's ulcer resection by microvascular transfer
of a burn-contracted little finger: a case report of spare part surgery.
AB - Thumb reconstruction after amputation due to a squamous cell carcinoma in a burn
scar sustained in infancy was accomplished by microvascular transfer of the
ipsilateral scar-contracted little finger. This transfer achieved a successful
functional and aesthetic thumb reconstruction and at the same time removed a
'cumbersome' little finger which had often snagged on things. This case
emphasises the merits of unused part transfer in hand reconstructive surgery,
made possible by microvascular techniques.
PMID- 9659118
TI - Reversed extensor indicis proprius muscle and dorsal wrist pain.
PMID- 9659119
TI - Achieving natural shading of the nostril in the reconstruction of a half nose.
AB - The secondary deformities in a patient who had a half nose that had been
reconstructed in childhood using a median forehead flap and the corrective
procedures subsequently employed are described. The secondary deformities
included elevation of the right alar rim and a completely visible nasal floor.
These deformities were corrected with a scalping forehead flap and by changing
the orientation of the reconstructed right nostril and nasal cavity. Nasal airway
reconstruction may not always be needed, particularly in a congenital half nose
such as described here. Instead, the aesthetic importance of the orientation of
the reconstructed nasal cavity in order to obtain a normal shaded appearance in
the nostril is emphasised.
PMID- 9659120
TI - Development of ganglioneuroma following successful treatment for orbital
rhabdomyosarcoma.
AB - A female infant presented with a left orbital embryonal rhabdomyosarcoma at the
age of 3 months. She was successfully treated for this tumour with chemo- and
radiotherapy. Eight years later she developed a ganglioneuroma in the same area
which was treated surgically, but recurred at the age of 19. Re-examination of
all of the specimens using immunohistochemistry confirmed that the initial and
successive diagnoses had been correct. Two further explanations for this rare
sequence of events are considered: whether the initial biopsy had been
unrepresentative of the whole tumour, or whether there had indeed been two
separate tumours arising in the same area. The theories of this previously
undocumented occurrence are discussed further.
PMID- 9659121
TI - Congenital partial absence of the facial muscles.
AB - Facial asymmetry in a newborn infant suggests various diagnoses, including birth
trauma and congenital hemifacial microsomia. But congenital absence or hypoplasia
of facial muscles has not been known except for the depressor anguli oris muscle
(DAOM). The authors' experience with surgical treatment of congenital hypoplasia
of the risorius, zygomaticus major and minor, and levator labii superioris
muscles is presented. Congenital facial muscle absence is uncommon. Although the
hypoplasia of the DAOM is known, this disease is not fully clarified. The authors
report a case of congenital partial palsy of the face in which some facial
muscles were absent although the facial nerve was normal.
PMID- 9659122
TI - Friction burns to thigh caused by tourniquet.
PMID- 9659123
TI - Aesthetic treatment of Romberg's disease with multiple implants of fragmented
Gore-Tex soft tissue patch.
PMID- 9659124
TI - Atypical presentation of cutaneous B-cell lymphoma.
PMID- 9659125
TI - Ritual sprinkling as a source of recurrent infection in a skin graft donor site.
PMID- 9659126
TI - Radiological management of venous thrombosis of the lower limb.
PMID- 9659127
TI - Contrast media-induced nephrotoxicity--questions and answers.
AB - The intravascular administration of contrast media (CM) can produce acute
haemodynamic changes in the kidney characterized by an increase in renal vascular
resistance and a decrease in the glomerular filtration rate (GFR). These changes
may lead to clinically significant reduction in renal function in patients with
pre-existing risk factors such as diabetic nephropathy, congestive heart failure
and dehydration. The pathophysiology of the renal haemodynamic effects of CM
involves activation of the tubuloglomerular feedback (TGF) mechanism and the
modulation of the intrarenal production of vasoactive mediators such as
prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is
osmolality-dependent and accounts for about 50% of the acute functional effects
of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous
vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM.
Endothelin and adenosine play a crucial role in mediating the acute functional
effects of CM. Antagonists of these mediators attenuate the reduction in renal
function induced by contrast agents. Vacuolization of the cells of the proximal
tubules and necrosis of those of the medullary ascending limbs of loops of Henle
are the main structural effects of CM in the kidney. The reduction in renal
function induced by CM could be minimized by the use of low osmolar CM and
adequate hydration. The prophylactic administration of calcium channel blockers
and adenosine antagonists such as theophylline may also offer some protective
effect.
PMID- 9659128
TI - Observer variation in plain radiography of the lumbosacral spine.
AB - In this study, interobserver and intraobserver variations in the interpretation
of plain radiographs of the lumbosacral spine were evaluated. Three radiologists
independently interpreted the radiographs from 200 consecutive outpatients, aged
13-93 years, mostly referred from general practitioners. Interobserver agreement
was best for vertebral fractures, osteopenia, spondylolisthesis at L5-S1,
lumbosacral junctional vertebra, reduced disc height at L4-S1 and osteophytes at
L2-S1 (kappa 0.61-0.95), and poorest for spina bifida of S1, degenerative
spondylolisthesis and facet joint arthrosis at T12-L4, sacroiliac joint
arthrosis, narrow central spinal canal, film quality, and for decisions
concerning evaluation of facet joints and spinal canal (kappa < 0.34). For
several diagnoses, the number of abnormal findings differed significantly between
observers (p < 0.05, McNemar's test), indicating different diagnostic thresholds.
Intraobserver agreement in 36 reevaluated patients was fair to excellent for
almost all variables (kappa > 0.46). Although some diagnoses related to low back
pain were quite consistently evaluated, the substantial disagreement on many
findings should alert clinicians and radiologists against overestimating the
validity and usefulness of the examinations. To improve diagnostic consistency,
it is important to reduce variation caused by different thresholds for
abnormality.
PMID- 9659129
TI - The effect of radiographic contrast media on human vascular smooth muscle cells.
AB - The relation between intravascular radiographic contrast media (RCM) and
myointimal hyperplasia after percutaneous transluminal angioplasty is not known.
We have investigated the cytotoxic effects of RCM on human vascular smooth muscle
cells (VSMCs) and their effect on the growth of these cells. The cytotoxic
effects of RCM were studied using human VSMCs. The cells after being grown to
confluency were exposed for 60 min to 250 mgI ml-1 of diatrizoate, ioxaglate,
iopromide, iotrolan and saturated mannitol solutions. The control group was
treated with only 15% fetal calf serum (FCS) containing medium. The viability of
the cells was examined using the trypan blue exclusion test. The effect of RCM on
growth was assessed by exposing the VSMCs after growth arrest, for either 15 or
60 min to 250 mgI ml-1 of diatrozoate, ioxaglate, iopromide, iotrolan and
saturated mannitol solution. There was no significant change in the viability of
the VSMCs after 60 min exposure to iopromide, iotrolan, saturated mannitol
solution, and after 15 min exposure to diatrizoate or ioxaglate. After exposure
to diatrizoate or ioxaglate for 60 min, 16.5 +/- 2.2% or 9.2 +/- 2.6% dead cells
were found, respectively (p < 0.05 versus control). In the growth assay of VSMCs,
diatrizoate, ioxaglate and saturated mannitol solutions reduced the growth rate
(p < 0.05 versus control). No significant change was observed with iopromide and
iotrolan. In conclusion, ionic RCM have cytotoxic and cytostatic effects on VSMCs
while non-ionic media have no effects. There is no direct stimulatory effect of
contrast media on the growth of VSMCs. The cytotoxic and cytostatic effects of
contrast media seems to be both osmolality and chemotoxicity dependent. Low
osmolar non-ionic RCM are not likely to contribute to the mechanisms responsible
for myointimal hyperplasia after angioplasty.
PMID- 9659130
TI - Colour Doppler flow in normal axillary lymph nodes.
AB - 81 women with carcinoma of the breast who underwent axillary nodal dissection
were studied pre-operatively with colour Doppler ultrasound. The presence of
colour Doppler flow was demonstrated in 83.6% of normal lymph nodes compared with
87.5% of metastatic lymph nodes. Using the presence of colour Doppler signal as
the sole diagnostic criterion for the diagnosis of metastasis gave a sensitivity
of 92.5%, specificity of 9.52%, accuracy of 50%, positive predictive value of
49.3% and negative predictive value of 57.1%. Using grey scale sonographic
criteria, where a metastatic node was defined as a node with loss of central
fatty hilum and/or eccentric cortical hypertrophy, a sensitivity of 79.5%,
specificity of 94.0%, accuracy of 87.6%, positive predictive value of 91.2% and
negative predictive value of 85.5% were obtained. Colour Doppler studies of the
axillary nodes in a second group of 106 women who attended for breast cancer
screening and had no significant breast or axillary pathology also showed colour
Doppler signal in 86.7% of nodes. It is concluded that colour Doppler flow
signals can be demonstrated in both normal and metastatic axillary lymph nodes,
and is highly non-specific when used as the sole diagnostic criterion in the
diagnosis of malignancy.
PMID- 9659131
TI - Intrasplenic venous flow patterns demonstrated by Doppler ultrasound in patients
with portal hypertension.
AB - The flow pattern in the splenic vein has been previously reported in patients
with portal hypertension, but with no reference to the flow within the
intrasplenic venous radicles. Using Doppler ultrasound, this study describes the
intrasplenic venous flow direction in 176 adult patients with intrahepatic portal
hypertension. In our series, a normal flow pattern was maintained in all except
four patients (2.3%) who had either reversed or dual venous drainage patterns
resulting in trans-splenic portosystemic shunts. These abnormal patterns are
Doppler signs of portal hypertension which might be associated with a higher risk
of oesophageal variceal bleeding. It is recommended that the intrasplenic venous
flow pattern should be assessed before surgical intervention involving the spleen
in patients with portal hypertension.
PMID- 9659132
TI - Comparison of the precision of two vertebral morphometry programs for the lunar
EXPERT-XL imaging densitometer.
AB - Comparative precision tests of the vertebral height measurement function of the
Aberdeen Vertebral Morphometry System (AVMS) software and Lunar EXPERT-XL
software were undertaken using four vertebrae from the same lateral spine dual
energy X-ray absorptiometry (DXA) image of the same subject (male, 67 years). Two
of the vertebrae were abnormal and two were normal. Three observers inexperienced
in morphometry and one experienced observer took part in the study. Repeatability
was obtained from 10 sequential measurements of the posterior, middle and
anterior heights at the same sitting by the same observer. Intraobserver
reproducibility compared the means of one set of measurements for all vertebrae
with another taken 1 week later. Interobserver reproducibility compared the means
of one set of measurements for all vertebrae from an experienced and an
inexperienced observer, and from two inexperienced observers. The AVMS software
had significantly higher (p < 0.05) repeatability (mean coefficient of
variability, CV = 3.5%) than the Lunar software (mean CV = 5%), significantly
higher (p < 0.01) intraobserver reproducibility (mean CV = 4.6%) than the Lunar
software (mean CV = 8.5%), and significantly higher (p < 0.05) interobserver
reproducibility (mean CV = 4.7%) than the Lunar software (mean CV = 7.5%). In
conclusion, the new AVMS method possessed higher precision when measuring both
abnormal and normal vertebrae and when used by both experienced and inexperienced
observers.
PMID- 9659133
TI - Radiation dose and diagnosticity of barium enema examinations by radiographers
and radiologists: a comparative study.
AB - With the current emphasis on the extension of the role of the radiographer,
radiographers in some hospitals now undertake some of the procedures
traditionally performed by radiologists. In the present study, dose-area product
(DAP) measurements for over 1000 barium enema examinations performed by
radiologists and radiographers were analysed and compared to ascertain whether
there were significant differences in the radiation dose to the patient,
depending on the category of staff performing the examination. All examinations
were reported by a radiologist. The radiologist's reports were analysed against
the known outcomes to compare the diagnosticity of the examination when carried
out by the two categories of staff. The study shows that although radiographers
are able to produce consistent diagnostic results, there is an increase in
patient dose due to extra films taken for reporting, which may be difficult to
justify. Measures for reducing the dose from this component of the examination
were explored.
PMID- 9659134
TI - An economic evaluation of the use of rare earth screens to reduce the radiation
dose from diagnostic X-ray procedures in Israel.
AB - In Israel the diffusion of rare earth screen technology has been limited. These
screens could halve the radiation dose to the patient from diagnostic X-ray
radiography, with little managerial effort and without being detrimental to the
quality of the diagnostic image. We estimated the total effective dose from
diagnostic film radiography capable of reduction by the use of rare earth
screens, based on the number of hospital and ambulatory diagnostic X-ray
procedures. This number was multiplied by the computed radiation dose per body
site for a series of diagnostic procedures. The annual dose was approximately
0.53 mSv per head, approximately half of which could be averted by the
introduction of rare earth screen technology. Based on a fatality risk of 3% Sv
1, it is estimated that the adoption of rare earth screen technology might reduce
the annual incidence of cancer by some 93 cases, half of which would be fatal
after an average latency period of 18.4 years. The cost of purchasing rare earth
screens on a nationwide basis is approximately $3.0 million. This cost is
outweighed by a saving of $9.6 million in X-ray tube replacement costs over the
period 1997-2006. Government legislation enforcing the use of rare earth screens
is essential, because of the lack of prestige associated with acquiring rare
earth technology, as well as institutional reluctance to accept the external
benefits of reduced morbidity and mortality and/or to extend budgetary time
horizons.
PMID- 9659135
TI - An image registration scheme applied to verification of radiation therapy.
AB - The introduction of modern conformal radiation therapy techniques requires high
geometric precision in treatment delivery which must be verified. For that
purpose we have developed an automated system based on registration of portal and
simulation (or planning) image pairs. The image registration is performed on
anatomical features which are automatically extracted from the portal image. The
portal image is then registered with a planning or simulation radiographic image
which represents the geometric prescription for the treatment, using an optimized
version of the chamfer matching algorithm. Subsequently, the magnitude of the
radiation field displacement during treatment is measured by registering the
prescribed and treated field boundaries. Algorithms based on chamfer matching and
polygon matching have been used for the field boundary registration. Performance
of the entire scheme was evaluated on a series of 15 portal images of a pelvic
phantom representing various known degrees of the radiation field displacement.
The measurements of the radiation field displacements performed by the automated
system proved very reliable and after correction for systematic bias agreed to
within 1.5 mm or 1 degree with the displacements applied. Second test series
involved comparisons between the automated registrations and those performed
manually/visually by an experienced human observer, on 31 portal images acquired
during treatments of 18 pelvic patients. These tests showed close agreement (in
80% of cases discrepancies were smaller than 1.5 mm or 1.5 degrees) between the
automated scheme and the human observer. It is concluded that the developed
scheme would be suitable for online geometric verification of radiation therapy
treatments.
PMID- 9659136
TI - Evaluation of peripheral dual energy X-ray absorptiometry: comparison with single
photon absorptiometry of the forearm and dual energy X-ray absorptiometry of the
spine or femur.
AB - An evaluation of the Osteoscan peripheral dual energy X-ray absorptiometer (pDXA)
was carried out to compare its performance with those of a single photon
absorptiometer (SPA) (Molsgaard Medical ND1100A) and a dual energy X-ray
absorptiometer (DXA) (Lunar DPX alpha) of the spine or femur. In 57 patients,
correlation between bone mineral content (BMC) of the forearm at the ultradistal
(UD) site by pDXA and by SPA was high (r = 0.94). Comparisons were also made with
spine and femur bone mineral density (BMD) DXA measurements. The correlation of z
scores of UD BMD with z-scores for lumbar spine L2-L4 was r = 0.63 (n = 73
patients); and with z-scores for neck of femur was r = 0.72 (n = 33). With the
Osteoscan the measurement error coefficient of variation in vivo was 2.6% for
BMC, 1.8% for BMD at the ultradistal site; 2.1% for BMC and 1.9% for BMD at the
mid-distal site. Repeat measurements were made of the European forearm phantom;
precision for SPA was slightly better than either pDXA or Lunar DXA. The
Osteoscan has the potential for a rapid throughput of patients and is not
affected by calcification and degenerative changes that can corrupt DXA
measurements on the anteroposterior spine in older women.
PMID- 9659137
TI - Enhancement of radiosensitivity of rat rhabdomyosarcoma R1H with normobaric
carbogen and hyperbaric oxygen (HBO) using conventionally fractionated
irradiation.
AB - Hypoxic clonogenic cells are an important contributory factor in tumour
radioresistance. The objective of the present study was to evaluate whether
hyperbaric oxygen enhances tumour radiosensitivity, using a conventionally
fractionated irradiation schedule, and whether the radiosensitizing potential is
different from carbogen. Experiments were performed using the rhabdomyosarcoma
R1H model transplanted subcutaneously in the flank of WAG/Rij rats. A total of 30
X-ray fractions of 2 Gy were given either in air, normobaric carbogen or high
pressure oxygen (HPO) (240 kPa, 2.37 atm) without anaesthesia. The time taken to
achieve complete remission was 38.7 +/- 3.6 days, 36.7 +/- 2.7 days and 32.4 +/-
4.1 days for air, normobaric carbogen and HBO, respectively. The differences
between air and HBO (p = 0.002) and carbogen and HBO (p = 0.015) were
significant. Use of carbogen and HBO produced the same local control probability
at 150 days and this was significantly higher than local control under ambient
conditions (p < 0.0001). It was concluded that the time to achieve complete
remission of the rat rhabdomyosarcoma R1H can be shortened by HBO. Furthermore,
both HBO and carbogen give higher local control probabilities than treatment
under ambient conditions when used with a conventionally fractionated radiation
schedule.
PMID- 9659138
TI - Primary synovial sarcoma of the gastrocolic ligament.
AB - A case of primary synovial sarcoma of the gastrocolic ligament is reported in a
37-year-old woman. CT showed an encapsulated intraabdominal cystic tumour with an
amorphous solid component. Barium studies showed a mass at the gastrocolic
ligament which elevated the gastric antrum and displaced the transverse colon
downwards. This is the first report of synovial sarcoma formation in the
gastrocolic ligament. This tumour may have originated from pluripotential
mesenchyme.
PMID- 9659139
TI - Middle cranial fossa arachnoid cysts: not always a benign entity.
AB - Arachnoid cysts are often discovered as incidental findings on cranial imaging. A
rare manifestation is described in a child presenting acutely with symptoms and
signs of raised intracranial pressure.
PMID- 9659140
TI - MRI of a giant splenic artery aneurysm.
AB - Aneurysms of the splenic artery larger than 3 cm are very rare. We present the
imaging features of a 12 cm, partially thrombosed splenic artery aneurysm. MRI
was valuable in establishing the diagnosis.
PMID- 9659141
TI - The vanishing heart--deterioration on chest radiography with clinical improvement
during prone position ventilation.
AB - Prone position ventilation is used in the treatment of ARDS. Its beneficial
effects are due to increased ventilation of the dorsal lung areas. Consequently,
the now dependent parts of the lungs collapse, resulting in decreased sharpness
of the cardiac silhouette. The latter may be misinterpreted as a worsening of the
cardiopulmonary condition while, in fact, gas exchange and ventilation may be
markedly improved. These features are illustrated in the case presented.
PMID- 9659142
TI - Anatomical communications of the perirenal space.
AB - There are controversies over the anatomical communications between the perirenal
space and the adjacent extraperitoneal spaces. Clinical studies, mainly based on
CT, show fluid collections extending into the adjacent space; into the bare area
of the liver on the right, into the superior extraperitoneal space on the left,
towards the midline from each perirenal space, and into the lower retroperitoneal
space of the abdomen and pelvis. There are certain constant anatomical barriers
limiting free extension of fluid or pathology. The pattern of fluid collection in
the perirenal space and extension into the adjacent extraperitoneal space is
relatively consistent although it varies with the amount and nature of the
pathological fluid collection. This pictorial review illustrates anatomical
barriers and CT findings of perirenal fluid collections and their extension into
adjacent extraperitoneal spaces.
PMID- 9659143
TI - Case of the month. In what's my line?
PMID- 9659144
TI - Discharge of microcalcification during a localization procedure.
PMID- 9659145
TI - Risk of childhood cancer from fetal irradiation.
PMID- 9659146
TI - Reductions in fluoroscopy screening times resulting from physician credentialling
and practice surveillance.
PMID- 9659147
TI - The relationship between autoimmune markers and different clinical syndromes in
autoimmune hepatitis.
PMID- 9659148
TI - Just how inflamed is the normal gut?
PMID- 9659149
TI - Intestinal metaplasia and the squamocolumnar junction: what does it all mean?
PMID- 9659150
TI - Shock news for the gut.
PMID- 9659151
TI - Altering cytokine soups: a recipe for inflammatory bowel disease?
PMID- 9659152
TI - Chemokines in the gastric mucosa in Helicobacter pylori infection.
AB - BACKGROUND: Although chemokines have been suggested to play an important role in
Helicobacter pylori associated gastritis, few studies have investigated the role
of chemokines other than interleukin 8 (IL-8) in gastric mucosa. AIMS: To
investigate the expression and production patterns of various chemokines using
gastric biopsy specimens. METHODS: In 192 patients, expression patterns of C-X-C
chemokines (IL-8 and growth regulated alpha (GRO alpha)) and C-C chemokines
(regulated on activation, normal T cell expressed and presumably secreted
(RANTES), monocyte chemotactic and activating factor (MCAF), macrophage
inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta) were examined using
reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked
immunosorbent assay (ELISA). cagA gene was identified using PCR. RESULTS: H
pylori infection was associated with increased rates of expression of mRNA for IL
8, GRO alpha, RANTES, and MIP-1 alpha and with increased levels of mucosal IL-8
and GRO alpha. IL-8 and GRO alpha levels correlated with the density of H pylori
in both the antrum and corpus. The levels of these chemokines correlated with
cellular infiltration in the antrum but not the corpus. cagA gene positive H
pylori infection was associated with increased rates of expression of mRNA for IL
8 and GRO alpha and with increased levels of these chemokines. CONCLUSION: H
pylori infection is associated with increased expression rates and production of
C-X-C chemokines (IL-8 and GRO alpha), but not with increased production of C-C
chemokines. Although H pylori infection is associated with increased C-X-C
chemokines in the antrum and corpus, there is a difference in the inflammatory
response between these two areas of the stomach.
PMID- 9659153
TI - Assessment of symptomatic response as predictor of Helicobacter pylori status
following eradication therapy in patients with ulcer.
AB - BACKGROUND: Helicobacter pylori eradication therapy is routinely used for
treating patients with peptic ulcer disease. AIMS: To assess the value of
symptomatic response to H pylori eradication therapy as a marker of post
treatment H pylori status. PATIENTS AND METHODS: One hundred and nine dyspeptic
patients with active duodenal or gastric ulceration association with H pylori
infection had their symptoms measured by a validated questionnaire before and
three months following H pylori eradication therapy. The symptomatic response was
compared with post-treatment H pylori status as determined by the 14C urea breath
test. RESULTS: An eradication rate of 84% was achieved. Of the 92 patients
eradicated of H pylori, 47% experienced complete or near complete resolution of
dyspepsia. Of the 17 patients in whom the infection was not eradicated, only one
(6%) experienced resolution of dyspepsia. Resolution of dyspepsia was therefore a
powerful predictor of eradication of H pylori with a predictive value of 98%. In
contrast, persistence of dyspepsia was a weak predictor of persisting infection
with a predictive value of only 25%. Excluding patients with endoscopic evidence
of coexisting oesophagitis and/or retrosternal discomfort or reflux at initial
presentation did not increase the predictive value of persisting dyspepsia for
persisting infection. CONCLUSIONS: Complete resolution of dyspeptic symptoms is a
powerful predictor of eradication of H pylori infection in ulcer patients.
Persistence of symptoms is a weak predictor of persisting infection and patients
with persisting dyspepsia must have their H pylori status rechecked to guide
future management.
PMID- 9659154
TI - Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small
intestine.
AB - BACKGROUND: Free radicals are associated with post-ischaemic intestinal injury
and contribute to major clinical problems primarily in premature infants. Various
antioxidative means and modes of intervention, previously tested, have
demonstrated only limited efficacy. AIMS: To study the protective activity of the
stable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl (TPL) and its
respective hydroxylamine (TPL-H) against ischaemia/reperfusion (I/R) injury.
METHODS: An isolated loop of ileum was created in laboratory male Sabra rats and
constantly perfused with warmed normal saline. Intestinal injury was elicited
through clamping of the superior mesenteric rat artery followed by reperfusion.
Either TPL or TPL-H was given intravenously immediately before ischaemia or
reperfusion and continuously afterwards. The rate of mucosal to lumen clearance
of para-aminohippurate (PAH) was used to evaluate intestinal mucosal injury.
Serum and perfusate levels of both TPL and TPL-H were measured using electron
paramagnetic resonance spectrometry. RESULTS: The increase in intestinal
permeability induced by I/R was significantly inhibited by both TPL and TPL-H.
The nitroxide was effective also when given immediately before reperfusion.
CONCLUSIONS: Through a continuous exchange, TPL and TPL-H act as self
replenishing antioxidants and thus protect from intestinal injury. This
demonstrates the potential of the family of nitroxide antioxidants against
oxidative stress in general and I/R injury in particular.
PMID- 9659155
TI - Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with
carcinoid diarrhoea.
AB - BACKGROUND: Carcinoid diarrhoea is associated with rapid small bowel and proximal
colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3)
antagonist restores postprandial colonic tone towards normal in carcinoid
patients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist,
alosetron, on symptoms, stool fat, and transit in patients with carcinoid
diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were
recorded daily and gastrointestinal transit was measured by scintigraphy in a
three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group,
four week study. Placebo was given during the first week. Loperamide (2 mg
capsules) was used as rescue medication. RESULTS: There were numerical
improvements in median diarrhoea score, stool weight, loperamide use, and overall
colonic transit at four hours, but no overall significant drug effect was shown.
Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable
comparisons), but did not significantly alter small bowel transit. CONCLUSIONS:
Alosetron retardation of proximal colonic emptying in patients with carcinoid
diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses
of alosetron higher than 2.0 mg twice daily will be required for symptomatic
benefit in carcinoid diarrhoea.
PMID- 9659156
TI - Cytokine profiles of cultured microvascular endothelial cells from the human
intestine.
AB - BACKGROUND AND AIMS: Cytokine production by endothelial cells, has, for practical
reasons, been chiefly studied in human umbilical vein endothelial cells (HUVEC)
but, because tissue-specific differences apparently exist, the role of human
intestinal microvascular endothelial cells (HIMEC) as a source of mucosal
cytokines was also assessed. METHODS: The expression of cytokine transcripts in
HIMEC was screened by means of reverse transcription polymerase chain reaction
(RT-PCR) and compared with cytokine profiles of HUVEC. Production of cytokines
was investigated by bioassay and enzyme linked immunosorbent assay (ELISA).
RESULTS: In the basal unstimulated state, HIMEC and HUVEC cultures contained
detectable mRNA for interleukin (IL)-3, IL-7, IL-8, IL-11, IL-14, IL-15, tumour
necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and
granulocytemacrophage colony stimulating factor (GM-CSF). However, message was
undetectable for IL-2, IL-4, IL-5, IL-9, IL-10, IL-12p40, IL-13, and interferon
(IFN)-gamma in the resting as well as the stimulated state. Stimulation of HIMEC
and HUVEC with recombinant human (rh) IL-1 beta or rhTNF-alpha induced cell
associated bioactive IL-1 alpha but not IL-1 beta, as well as enhanced secretion
of both IL-6 and IL-8. Furthermore, transcript levels for GM-CSF and TNF-alpha
were enhanced by rhIL-1 beta or rhTNF-alpha in both cell types. Supernatants from
Th1-like or Th0-like gluten reactive intestinal T cell clones derived from
patients with coeliac disease elicited cytokine profiles in both HIMEC and HUVEC
similar to those revealed after rhIL-1 beta or rhTNF-alpha stimulation.
CONCLUSIONS: These data demonstrate that the intestinal microvascular endothelium
may contribute to the cytokine network of the intestinal mucosa with the ability
to respond to locally generated cytokines and to produce potent inflammatory
mediators.
PMID- 9659157
TI - Spontaneous secretion of interferon gamma and interleukin 4 by human
intraepithelial and lamina propria gut lymphocytes.
AB - BACKGROUND: Cytokines secreted by intestinal T lymphocytes probably play a
critical role in regulation of the gut associated immune responses. AIMS: To
quantify interferon gamma (IFN-gamma) and interleukin 4 (IL-4) secreting cells
(SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from
the duodenum and right colon in non-pathological situations and in the absence of
in vitro stimulation. PATIENTS: Duodenal and right colonic biopsy specimens were
obtained from patients with no inflammation of the intestinal mucosa. METHODS:
Intraepithelial and lamina propria cell suspensions were assayed for numbers of
cells spontaneously secreting IFN-gamma and IL-4 by a two site reverse enzyme
linked immunospot technique (ELISPOT). RESULTS: The relatively high proportion of
duodenal lymphocytes spontaneously secreting IFN-gamma (IEL 3.6%; LPL 1.9%) and
IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously
IFN-gamma SC and the absence of spontaneously IL-4 SC among peripheral blood
mononuclear cells. In the basal state, both IFN-gamma and IL-4 were mainly
produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN
gamma in the basal state, and 0.1% secreted IL-4. CONCLUSIONS: Compared with
peripheral lymphocytes substantial proportions of intestinal epithelial and
lamina propria lymphocytes spontaneously secrete IFN-gamma and/or IL-4. These
cytokines are probably involved in the normal homoeostasis of the human
intestinal mucosa. Disturbances in their secretion could play a role in the
pathogenesis of gastrointestinal diseases.
PMID- 9659158
TI - Tumour necrosis factor-alpha enhances intraepithelial lymphocyte proliferation
and migration.
AB - BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory
cytokine found in abundance in diseased intestine. AIMS: The T cell production of
TNF-alpha and the impact of this cytokine on intestinal T cell proliferation,
migration, and cytotoxicity were studied. METHODS: Intestinal lymphocytes from
normal jejunum were used. TNF-alpha production in culture supernates was measured
by enzyme linked immunosorbent assay (ELISA). Lymphocyte proliferation was
measured using 3H thymidine uptake; migration, using transwell chambers; and
cytotoxicity of HT-29 colon cancer cells, using the chromium-51 release assay.
RESULTS: TNF-alpha was produced mainly by the CD8+ T cells in the intraepithelial
lymphocytes (IEL) and the CD4+ T cells in the lamina propria lymphocytes in
response to CD2 stimulation: 478 (94) and 782 (136) pg/ml, respectively. TNF
alpha (1 ng/ml or greater) augmented proliferation of IEL in response to
interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that
did not involve IL-2 production or receptor generation. Conversely, antibody to
TNF-alpha reduced IEL proliferation in response to IL-2 or IL-7. TNF-alpha also
induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous
migration). TNF-alpha had no effect on lymphokine activated killer cell activity.
CONCLUSIONS: TNF-alpha increases the proliferation and migration of IEL, which
may expand their number in the epithelium.
PMID- 9659159
TI - Effects of smoking on the urine excretion of oral 51Cr EDTA in ulcerative
colitis.
AB - BACKGROUND: Smokers have a reduced risk and ex-smokers an increased risk of
ulcerative colitis (UC). Stopping smoking often precedes onset and relapses.
Smoking reduces the 24 hour urine excretion of oral chromium-51 labelled EDTA in
healthy individuals. AIMS: To estimate the effects of smoking on the urine
excretion of oral 51Cr EDTA in well characterised patients with UC. SUBJECTS:
Sixteen smoking and 16 non-smoking patients with UC in remission were studied.
The non-smokers had never smoked. Most were taking 5-aminosalicylic acid. No
patient took steroids or immunosuppressants. The control group comprised 25
smoking healthy volunteers and 25 who had never smoked. The median cigarette
consumption was equal in the patients and volunteers. METHODS: The 24 hour urine
excretion of oral 51Cr EDTA was measured and the results were correlated with
smoking habits, number of cigarettes, and disease extent. RESULTS: Patients with
UC had significantly higher 24 hour urine recoveries than healthy controls (p =
0.04). This difference was more pronounced when patients who smoked were compared
with healthy smokers (p = 0.005) No significant differences were found when
comparing non-smoking patients with non-smoking controls or when comparing
smoking and non-smoking patients. Urine recoveries did not correlate with number
of cigarettes or disease extent. Smoking was more prevalent in patients with a
more limited disease extent (p = 0.033). CONCLUSIONS: Effects of smoking on the
urine excretion of 51Cr EDTA in health were abolished by the presence of UC. The
protective effects of smoking in established UC are not due to a moderating
effect of smoking on intestinal permeability.
PMID- 9659160
TI - Short segments of Barrett's epithelium and intestinal metaplasia in normal
appearing oesophagogastric junctions: the same or two different entities?
AB - BACKGROUND: Endoscopic diagnosis of short segments of Barrett's epithelium
(SSBE)' is difficult and its meaning in terms of the presence of specialised
columnar epithelium (SCE) has not been prospectively evaluated. AIMS: To evaluate
the prevalence of SCE in patients with an endoscopic diagnosis of SSBE and in
individuals with normal appearing oesophagogastric junctions, and to compare the
clinical characteristics of these two groups. PATIENTS: Thirty one patients with
an endoscopic diagnosis of short Barrett's oesophagus, less than 3 cm in length
(group A), and 44 consecutive patients with normal appearing oesophagogastric
junctions (group B). METHODS: Multiple biopsies were performed in suspicious
epithelium and at the oesophagogastric junction in groups A and B, respectively.
RESULTS: Age and sex distribution were similar in both groups. Reflux symptoms
were more frequent in group A (p < 0.001), as were endoscopic and histological
signs of oesophagitis (p < 0.001 and p = 0.001, respectively). SCE was found in
61.3% of group A patients compared with 25% in group B (p < 0.002), with men
predominating in group A while women were more frequent in group B (p = 0.02).
The differences in reflux symptoms and endoscopic/histological oesophagitis
remained significant. CONCLUSIONS: These results show that endoscopic diagnosis
of SSBE is associated with a high prevalence of SCE, significantly higher than
that found in normal appearing oesophagogastric junctions. Differences between
patients with SCE in the two groups suggest they may represent two different
entities.
PMID- 9659161
TI - Clonal analysis of isolated intestinal metaplastic glands of stomach using X
linked polymorphism.
AB - BACKGROUND: Monoclonal precancerous cells undergo successive biochemical and
genetic changes during the multistep process of carcinogenesis in the
gastrointestinal tract. Despite a high association with intestinal-type stomach
cancer (differentiated adenocarcinoma of the stomach), the role of intestinal
metaplasia is unclear in stomach carcinogenesis. AIMS: To study the clonality of
intestinal metaplasia. METHODS: The clonality of 86 single intestinal metaplastic
glands isolated by EDTA treatment from gastrectomy specimens from patients with
cancer were investigated. The methylation sensitive restriction enzyme HpaII and
polymerase chain reaction (PCR) were used to detect a polymorphic human androgen
receptor gene locus linked to an inactive X chromosome. RESULTS: Forty one (48%)
intestinal metaplastic glands were heterotypic (mixed cells of different allelic
methylation) and 45 (52%) were homotypic (cell population of the same allelic
methylation), while almost all the single pyloric glands were homotypic. Eleven
of 13 intestinal metaplastic mucosae that were 6 mm in diameter contained glands
that had originated from different cells. There were no strong relationships
between clonal type and location or histological type of intestinal metaplasia.
CONCLUSION: Intestinal metaplasia in general is not a lesion that arises or
proceeds monoclonally.
PMID- 9659162
TI - Somatic mutations, acetylator status, and prognosis in colorectal cancer.
AB - BACKGROUND: Somatic mutations in K-ras and TP53 may be associated with both
acetylator status and prognosis in colorectal cancer. AIMS: To determine whether
cancers with somatic mutations are more frequent in fast acetylators and whether
mutations or acetylator status influence prognosis after colorectal surgery.
PATIENTS: One hundred consecutive subjects undergoing elective surgery for
colorectal cancer. METHODS: Acetylator status was determined by polymerase chain
reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2)
gene. Mutations in K-ras (codon 12) and TP53 were determined by PCR analysis
using restriction enzyme digestion and single strand conformation polymorphism
respectively. Survival from colorectal cancer for up to five years after
diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox
proportional hazards regression was used to compare survival rates after
adjusting for tumour stage. RESULTS: Mutations in K-ras and TP53 were independent
of acetylator status. By log rank test, survival was significantly reduced in
subjects with TP53 mutations (p = 0.003) but was not significantly related to
acetylator status or the presence of K-ras mutations. After adjustment for tumour
stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality
(95% confidence interval 1.5 to 11.6) when compared with that of a TP53 negative
reference group. CONCLUSION: The presence of both TP53 and K-ras mutations in
colorectal tumours is an adverse prognostic marker which is independent of tumour
stage.
PMID- 9659163
TI - Morphology of sporadic colorectal cancer with DNA replication errors.
AB - BACKGROUND: Up to 15% of colorectal cancers are characterised by DNA
microsatellite instability (MIN), shown by the presence of DNA replication errors
(RERs). AIMS: To identify pathological features that are discriminating for
colorectal cancer (CRC) showing extensive MIN. SUBJECTS: A prospective series of
303 patients with CRC and no family history of either familial adenomatous
polyposis or hereditary non-polyposis colorectal cancer. METHODS: DNA was
extracted from fresh tissue samples and the presence of MIN was studied at nine
loci that included TGF beta RII, IGFIIR, and BAX. The 61 cases showing RERs were
compared with 63 RER negative cases with respect to a comprehensive set of
clinical and pathological variables. Predictive utility of the variables was
tested by decision tree analysis. RESULTS: Twenty seven patients with CRC showed
extensive RERs (three loci or more) (RER+) and 34 had limited RERs only (28 = one
locus; 6 = two loci) (RER+/-), yielding a bimodal distribution. RER+ cancers
differed from RER- and RER+/-) cases. Tumour type (adenocarcinoma, mucinous
carcinoma, and undifferentiated carcinoma) (p = 0.001), tumour infiltrating
lymphocytes (p = 0.001), and anatomical site (p = 0.001) were the most
significant of the discriminating variables. Algorithms developed by decision
tree analysis allowed cases to be assigned to RER+ versus RER- and +/- status
with a global sensitivity of 81.5%, specificity of 96%, and overall accuracy of
93%. CONCLUSIONS: Pathological examination of CRC allows assignment of RER+
status; assignment is specific and relatively sensitive. Conversely RER- and
RER+/- CRC are indistinguishable.
PMID- 9659164
TI - Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.
AB - BACKGROUND: Serrated adenoma is a new morphological subtype of colorectal
adenoma. The lesion provides a distinct morphological route to carcinoma, but the
underlying genetic changes have not yet been investigated. AIMS: To determine the
frequency of K-ras mutation in serrated adenoma. METHODS: The frequency of K-ras
codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic
polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
RESULTS: Although most of the serrated adenomas were large (average size 11.4 mm)
and polypoid, K-ras codon 12 point mutation was detected in only one of the 20
(5%), which is a significantly lower frequency than that in sporadic polypoid
adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical
hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of
carcinoma in situ, indicating their malignant potential and the existence of a
serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of
carcinoma in situ. CONCLUSIONS: K-ras mutation is uncommon in serrated adenomas,
indicating a different spectrum of genetic alterations in these lesions from
those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma
represents a new genetic pathway in the histogenesis of colorectal carcinoma.
PMID- 9659165
TI - Small bowel transit of a bran meal residue in humans: sieving of solids from
liquids and response to feeding.
AB - BACKGROUND: Ileal motor patterns are adapted to the propulsion of viscous meal
residue, such as bran, which accumulates in the distal ileum postprandially.
AIMS: To examine the effects of a second liquid/solid meal on ileal emptying.
SUBJECTS AND METHODS: Eleven healthy fasting subjects consumed a 1.47 MJ pancake
containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A).
Gastric emptying and transit through the left upper quadrant (proximal) and right
lower quadrant (distal) small bowel regions and colon were assessed
scintigraphically. Transit was compared with and without a second Indium-111
liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first
meal. RESULTS: Gastric emptying of meal A was slower than meal B (the time for
50% of the activity to leave the stomach (T50) being 113 (11) minutes versus 48
(3) minutes respectively, p < 0.01, n = 11). Both meals passed rapidly through
the proximal small bowel (T50 meal A = 57 (14) minutes versus T50 meal B = 42
(11) minutes). Transit of meal A through the distal small bowel was much slower
(T50 more than 390 minutes versus 176 (29) minutes for meal B, p < 0.01),
resulting in meal B overtaking meal A and entering the colon earlier. Ingestion
of the second meal (B) resulted in significantly less meal A marker entering the
colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p < 0.05,
n = 8). CONCLUSIONS: The distal small bowel selectively retains bran, allowing
liquid phase markers through to the colon. Consuming a second liquid/solid meal
does not stimulate ileal transit of bran which seems to be propelled quicker by
fasting motor patterns.
PMID- 9659166
TI - Identification of distinct upper and lower gastrointestinal symptom groupings in
an urban population.
AB - BACKGROUND: The current classification dividing patients with functional
gastrointestinal symptoms into subgroups remains controversial. AIMS: To
determine whether distinct symptom groupings exist in the community. METHODS: A
random sample of Sydney residents in Penrith, Australia was mailed a validated
self report questionnaire. Gastrointestinal symptoms including the Rome criteria
for irritable bowel syndrome (IBS) and dyspepsia were measured. RESULTS: Among
730 respondents, the 12 month age and gender adjusted prevalence (adjusted to the
Australian population) of IBS, dyspepsia, and gastro-oesophageal reflux were
11.8% (95% confidence interval (CI) 9.3 to 14.3%), 11.5% (95% CI 9.6 to 14.6%),
and 17.5% (95% CI 14.2 to 19.9%), respectively. In total, 60% of the population
reported four or more gastrointestinal symptoms. There was considerable overlap
of IBS with dyspepsia and among the dyspepsia subgroups by application of the
Rome criteria. Independently, 10 symptom groupings were identified by factor
analysis. The underlying constructs measured by these factors were generally the
major abdominal syndromes recognised by the Rome classification: dyspepsia, IBS,
reflux, painless constipation, painless diarrhoea, and bloating, in addition to a
number of more specific symptom groupings. CONCLUSION: Gastrointestinal symptoms
are common and overlap in the community, but distinct upper and lower abdominal
symptom groupings can be identified.
PMID- 9659167
TI - The endothelin receptor antagonist bosentan restores gut oxygen delivery and
reverses intestinal mucosal acidosis in porcine endotoxin shock.
AB - BACKGROUND: Endothelin-1, the most potent vasoconstrictor known, is produced in
septic states and may be involved in the pathophysiology of the deteriorated
splanchnic circulation seen in septic shock. AIMS: To elucidate the capability of
bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate
splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in
endotoxic shock. METHODS: In 16 anaesthetised pigs, central and regional
haemodynamics were monitored by thermodilution and ultrasonic flow probes,
respectively. A tonometer in the ileum was used for measurement of mucosal pH.
Onset of endotoxin challenge was followed by bosentan administration (to eight
pigs) two hours later. RESULTS: Endotoxin infusion reduced cardiac index and
systemic oxygen delivery; bosentan restored these parameters. The reduced mean
arterial blood pressure and renal blood flow remained unaffected by bosentan. The
profound reduction in gut oxygen delivery in response to endotoxin was completely
abolished by bosentan. Bosentan significantly improved the notably deteriorated
intestinal mucosal pH and mucosal-arterial PCO2 gap. The mucosal-portal vein PCO2
gap, used to monitor the mucosa in relation to the gut as a whole (including the
spleen and pancreas), was also greatly increased by endotoxaemia and
significantly reversed by bosentan. CONCLUSION: Bosentan completely restored the
profound endotoxin induced reductions in systemic and gut oxygen delivery with a
concomitant reversal of intestinal mucosal acidosis. Results suggest that
endothelin is involved in the pronounced perfusion disturbances seen in the gut
in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic
shock.
PMID- 9659168
TI - Management of occluded biliary Wallstents.
AB - BACKGROUND: Wallstents (Schneider Stent, Inc., USA) used for the palliation of
malignant biliary strictures, although associated with prolonged patency, can
occlude. There is no consensus regarding the optimal management of Wallstent
occlusion. AIMS: To evaluate the efficacy of different endoscopic methods for
managing biliary Wallstent occlusion. METHODS: A multicentre retrospective study
of patients managed for a biliary Wallstent occlusion. RESULTS: Data were
available for 38 patients with 44 Wallstent occlusions, all of which had initial
endoscopic management. Twenty four patients had died and 14 were alive after a
median follow up of 231 (30-1095) days following Wallstent occlusion. Occlusions
were managed by insertion of another Wallstent in 19, insertion of a plastic
stent in 20, and mechanical cleaning in five. Endoscopic management was
successful in 43 (98%). Following management of the occlusion, bilirubin
decreased from 6.0 (0.5-34.3) to 2.1 (0.2-27.7) mg/100 ml (p < 0.05). No
complications occurred. The median duration of second stent patency was 75 days
(95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days
(71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after
mechanical cleaning (NS). The respective median survivals were 70 days (22-118),
98 days (54-142), and 34 days (30-380) (NS). Incremental cost effective analysis
showed that plastic stent insertion is the most cost effective option.
CONCLUSION: Although all three methods are equally effective in managing an
occluded Wallstent, the most cost effective method appears to be plastic stent
insertion.
PMID- 9659169
TI - Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative
colitis? A population based case control study.
AB - BACKGROUND: Colonoscopic surveillance is a standard procedure in many patients
with long standing, extensive ulcerative colitis (UC), in order to avoid death
from colorectal cancer. No conclusive proof of its benefits has been presented
however. AIMS: To evaluate the association between colonoscopic surveillance and
colorectal cancer mortality in patients with UC. PATIENTS: A population based,
nested case control study comprising 142 patients with a definite UC diagnosis,
derived from a study population of 4664 patients with UC, was conducted. METHODS:
Colonoscopic surveillance in all patients with UC who had died from colorectal
cancer after 1975 was compared with that in controls matched for age, sex,
extent, and duration of the disease. Information on colonoscopic surveillance was
obtained from the medical records. RESULTS: Two of 40 patients with UC and 18 of
102 controls had undergone at least one surveillance colonoscopy (relative risk
(RR) 0.29, 95% confidence interval 0.06 to 1.31). Twelve controls but only one
patient with UC had undergone two or more surveillance colonoscopies (RR 0.22,
95% confidence interval 0.03 to 1.74), indicating a protective dose response
relation. CONCLUSION: Colonoscopic surveillance may be associated with a
decreased risk of death from colorectal cancer in patients with long standing UC.
PMID- 9659170
TI - Evidence for altered hepatic matrix degradation in genetic haemochromatosis.
AB - BACKGROUND: Altered matrix degradation contributes to fibrosis in some liver
diseases but the role of matrix degradation in fibrogenesis associated with
genetic haemochromatosis has not previously been addressed. AIMS: To measure
serum concentrations of tissue inhibitor of metalloproteinase 1 (TIMP-1) and
matrix metalloproteinases (MMP), MMP-1, MMP-2, and MMP-3 in patients with
haemochromatosis and control subjects. PATIENTS: Forty patients with
haemochromatosis and 19 healthy control subjects. Ten of the 40 patients were
studied before and after venesection therapy. METHODS: Serum levels of TIMP-1,
MMP-1, MMP-2, and MMP-3 were measured by enzyme immunoassay and correlated to
hepatic iron concentration and degree of histological fibrosis. RESULTS: Serum
TIMP-1 was increased in patients with haemochromatosis compared with controls
(163 (30) versus 123 (28) ng/ml, p < 0.0002). Mean serum TIMP-1 concentration of
patients with haemochromatosis without fibrosis was significantly higher than in
controls (153 (16) versus 123 (28) ng/ml, p = 0.03). Serum TIMP-1 concentration
correlated with both hepatic iron concentration and hepatic iron index (r = 0.42,
p < 0.01; r = 0.42, p < 0.01). Serum MMP-2 concentrations correlated with
increasing degree of fibrosis in patients with haemochromatosis (r = 0.38, p =
0.01). The mean MMP-1: TIMP-1, MMP-2:TIMP-1 and age/sex matched MMP-3:TIMP-1
ratios were significantly lower in patients with haemochromatosis than controls
(0.11 (0.06) versus 0.2 (0.14), p = 0.02; 3.32 (0.9) versus 3.91 (0.81), p =
0.05; and 0.26 (0.12) versus 0.47 (0.27), p = 0.007, respectively). Following
venesection, MMP-2 and MMP-3 concentrations increased by 11% (p = 0.03) and 19%
(p = 0.03), respectively. CONCLUSIONS: This study provides the first evidence of
an alteration in matrix degradation in haemochromatosis that may be a
contributing factor to hepatic fibrogenesis in this disease.
PMID- 9659171
TI - Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1
concentrations in type 2 autoimmune hepatitis.
AB - BACKGROUND: Liver/kidney microsomal antibody type 1 (LKM1) and liver cytosol
antibody type 1 (LC1) are the serological markers of type 2 autoimmune hepatitis
(AIH). AIMS: Since LKM1 and LC1 react against two distinct liver specific
autoantigens (cytochrome P450IID6 (CYP2D6) and a 58 kDa cytosolic polypeptide
respectively), the aim was to see whether LKM1 and LC1 concentrations correlate
with liver disease activity. PATIENTS: Twenty one patients with type 2 AIH were
studied. METHODS: All sera were tested by indirect immunofluorescence,
counterimmunoelectrophoresis, and immunoblotting visualised by enhanced
chemiluminescence. To evaluate LKM1 and LC1 levels, the 50 kDa microsomal
reactivity (corresponding to CYP2D6) and the 58 kDa cytosolic reactivity were
quantified by densitometric analysis. RESULTS: Seven patients were positive for
LKM1, nine for LC1, and five for both. Serial serum samples at onset and during
immunosuppressive treatment were analysed in 13 patients (four positive for LKM1,
six positive for LC1 and three positive for both). During remission, LKM1
concentration remained essentially unchanged in six of seven patients, and
decreased in only one. Conversely, in two of nine patients, LC1 was completely
lost, and, in the remaining seven, LC1 concentration was reduced by more than
50%. After immunosuppression tapering or withdrawal, flare ups of liver necrosis
ensued with increasing LC1 concentration, but not LKM1. CONCLUSIONS: LC1
concentration, at variance with that of LKM1, parallels liver disease activity,
and its participation in the pathogenic mechanisms of liver injury can be
hypothesised.
PMID- 9659172
TI - The liver in systemic amyloidosis: insights from 123I serum amyloid P component
scintigraphy in 484 patients.
AB - BACKGROUND AND AIMS: The liver is frequently involved in amyloidosis but the
significance of hepatic amyloid has not been systematically studied. We have
previously developed scintigraphy with 123I serum amyloid P component (123I-SAP)
to identify and monitor amyloid deposits quantitatively in vivo and we report
here our findings in hepatic amyloidosis. METHODS: Between 1988 and 1995, 805
patients with clinically suspected or biopsy proven systemic amyloidosis were
evaluated. One hundred and thirty eight patients had AA amyloidosis, 180 had AL
amyloidosis, 99 had hereditary amyloid syndromes, and 67 had dialysis related
(beta 2 microglobulin) amyloid. One hundred and ninety two patients with
amyloidosis were followed for six months to eight years. RESULTS: Hepatic amyloid
was found in 98/180 (54%) AL and 25/138 (18%) AA patients but in only 1/53
patients with familial transthyretin amyloid polyneuropathy and in none with
dialysis related amyloidosis. There was complete concordance between hepatic SAP
scintigraphy and the presence or absence of parenchymal amyloid deposits on liver
histology. Amyloidosis was never confined to the liver. Mortality was rarely due
to hepatic failure, although hepatic involvement with AA amyloid carried a poor
prognosis. Successful therapy to reduce the supply of amyloid fibril protein
precursors was followed by substantial regression of all types of amyloid.
CONCLUSIONS: SAP scintigraphy is a specific and sensitive method for detecting
and monitoring hepatic amyloid. Liver involvement is always associated with major
amyloid in other organ systems and carries a poor prognosis in AA type.
Appropriate therapy may substantially improve prognosis in many patients.
PMID- 9659173
TI - In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and
electron microscopy in chronic ductopenic rejection of human liver allografts.
AB - BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS)
provides non-invasive information about phospholipid metabolism. AIMS: To
delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR)
and to characterise spectral changes by in vitro MRS and electron microscopy.
PATIENTS AND METHODS: Sixteen liver transplant recipients (four with CDR; 12 with
good graft function) and 29 controls (23 healthy volunteers; six patients with
biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of
phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide
triphosphates (NTP) were measured. In vitro MRS and electron microscopy were
performed on biopsy specimens from five patients with CDR, freeze clamped at
retransplantation. Phosphoethanolamine (PE), phosphocholine (PC),
glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC)
concentrations were measured. RESULTS: The 12 patients with good graft function
displayed no spectral abnormalities in vivo; the four patients with CDR showed
significantly elevated PME:NTP (p < 0.01) and PDE:NTP ratios (p < 0.005).
Patients with biliary strictures had significant differences in PME:NTP (p <
0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR
patients showed elevated PE and PC, mirroring the in vivo changes in PME, but
reduced GPE and GPC concentrations were observed, at variance with the in vivo
PDE findings. On electron microscopy, there was no proliferation in hepatocyte
endoplasmic reticulum. CONCLUSIONS: The increase in PME:NTP reflects altered
phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may
represent a significant contribution from bile phospholipid.
PMID- 9659174
TI - Outcome of orthotopic liver transplantation in patients with haemophilia.
AB - BACKGROUND: Many patients with haemophilia have developed cirrhosis or
hepatocellular carcinoma due to transfusion acquired chronic viral hepatitis.
AIMS: To assess the long term outcome of all haemophilic patients reported to
have undergone orthotopic liver transplantation. METHODS: Transplant centres of
patients identified by medical database search were contacted and survival data
assessed by Kaplan-Meier analysis. RESULTS: Twenty six haemophilic men (median
age 46 years, range 5-63 years) underwent orthotopic liver transplantation in 16
centres between 1982 and 1996. Indications for transplantation were hepatitis C
cirrhosis (69%), hepatitis B with or without C cirrhosis (15%), viral hepatitis
related hepatocellular carcinoma (12%), and biliary atresia (4%). Six patients
(23%) were infected with human immunodeficiency virus (HIV). Postoperatively, the
median time to normal clotting factor levels was 24 hours (range 0-48 hours) and
exogenous clotting factors were stopped at a median of 24 hours (range 0-480
hours). Four patients (15%) had bleeding complications. The one and three year
survival of HIV positive recipients (67% and 23%) was significantly poorer (p =
0.0003) than that of HIV negative recipients (90% and 83%). Coagulopathy was
cured in all patients surviving more than 12 days post-transplant. Six of the 20
patients (30%) with hepatitis C cirrhosis pretransplant had evidence of disease
recurrence at a mean of nine months post-transplant. CONCLUSIONS: Hepatitis C
cirrhosis is the most common indication for orthotopic liver transplantation in
patients with haemophilia. Transplantation results in long term cure of
haemophilia but may be complicated by the effects of HIV infection or recurrent
viral hepatitis.
PMID- 9659175
TI - Tranexamic acid for severe bleeding gastric antral vascular ectasia in cirrhosis.
AB - BACKGROUND: It is believed that severe portal hypertensive gastropathy probably
accounts for most non-variceal bleeding episodes in patients with cirrhosis.
Gastric antral vascular ectasia (GAVE) also occurs in these patients. It is not
clear whether it is a variant of portal hypertensive gastropathy or a distinct
condition. PATIENT: A patient, a 66 year od woman, with cirrhosis initially
diagnosed as having portal hypertensive gastropathy and subsequently classified
as GAVE is described. She required transfusion with a total of 130 units of
packed red cells for gastrointestinal blood loss. RESULTS: The bleeding did not
respond to portal decompression with TIPS or beta blockers. Following treatment
with oral tranexamic acid she has not required further blood transfusion over a
period of 30 months. CONCLUSION: Tranexamic acid may be a useful treatment for
refractory bleeding due to gastric antral vascular ectasia in patients with
cirrhosis.
PMID- 9659176
TI - Autoantibodies against subunits of pyruvate dehydrogenase and citrate synthase in
a case of paediatric biliary cirrhosis.
AB - In a newborn girl with a history of connatal liver damage, histological
examination of a liver biopsy sample taken during the seventh week of life
revealed incipient destruction of bile ducts. Very high titres of
antimitochondrial antibodies were later detected in the plasma. As the hepatic
injury tended towards fibrosis, the histological diagnosis became primary biliary
cirrhosis. Autoantibodies against E1 alpha, E2, and E3 subunits and protein X
component of pyruvate dehydrogenase complex, and against citrate synthase were
detected on western immunoblotting in a 1 in 1000 dilution of the patient's
serum. The patient died of her illness at 11 years of age. In liver specimens
obtained at autopsy human immunoglobulin deposition was detected on the surface
of almost all hepatic cells by immunohistology. As there is a physical and
functional interaction between pyruvate dehydrogenase and citrate synthase within
the mitochondria, the presence of autoantibodies against certain proteins in the
patient suggests that in this form of the disease the molecular recognition and
then the autoimmunisation process could be directed against a mitochondrial
enzyme cluster containing both pyruvate dehydrogenase and citrate synthase.
PMID- 9659177
TI - The aging stomach.
PMID- 9659178
TI - Helicobacter pylori: beware "blind" eradication!
PMID- 9659179
TI - Are complications of endoscopic sphincterotomy age related?
PMID- 9659180
TI - History of dyspepsia in patients with gastric cancer.
PMID- 9659181
TI - The genetics of ulcerative colitis based on one Swede.
PMID- 9659182
TI - Iron reduction therapy in hepatitis C.
PMID- 9659183
TI - Grading of cardiac transplant rejection.
PMID- 9659184
TI - Cardiac output in 1998.
PMID- 9659185
TI - Hypertension.
PMID- 9659186
TI - Cell adhesion molecules in cardiovascular disease: a clinical perspective.
AB - In summary, there is increasing evidence that cell adhesion molecules play an
important role in cardiovascular pathology. They are involved in the main
processes that underlie cardiac disease including thrombosis, leucocyte
infiltration, smooth muscle proliferation, and cell migration. Anti-integrin
treatment is already widely used to treat thrombotic complications, and it seems
likely that manipulation of other cell adhesion molecules will be used clinically
in the near future.
PMID- 9659187
TI - Revision of the 1990 working formulation for cardiac allograft rejection: the
Sheffield experience.
AB - OBJECTIVE: To audit the 1990 International Society for Heart and Lung
Transplantation cardiac rejection criteria and to evaluate the impact on
classification and clinical outcomes of a modification in which grade 2 is
abolished and grades 1A and 1B are amalgamated into a single "grade 1." METHODS:
1652 heart biopsies were reviewed over a four year period. The initial 1348
biopsies (group 1), using the original 1990 criteria, were analysed in terms of
diagnostic grade and compared with the 304 biopsies analysed with the modified
scheme (group 2). Differences in grading with the 1990 scheme were compared
between two groups (1.1 and 1.2) reflecting early and late experience with
grading. Subsequently all the grade 2 and grade 1B biopsies were rescored in
terms of the modified scheme. Clinical results in terms of actuarial patient
survival at one year and freedom from 3A rejection were similarly audited.
RESULTS: The relative ratios of potentially significant rejection (grade 3A, 3B,
4) remained constant over the entire study in groups 1.1, 1.2, and 2. A 50%
reduction in grade 2 biopsy reporting was noted comparing early and late parts of
group 1. At subsequent review of the group 1 grade 2 biopsies, 97% could be
reassigned to grades 0 or 1 in the modified scheme, with the majority of these
diagnoses reflecting Quility effect/biopsy site reactions. Two cases (3%) of the
77 grade 2 biopsies were regraded as grade 3A rejection, with both occurring
within three months of transplantation. None of the grade 1B biopsies had high
grade cardiac rejection on review, most of these biopsies similarly showing
pronounced Quility effect and biopsy site reactions. Actuarial survival at one
year rose from 86% to 90% during the study, with freedom from 3A rejection
remaining unchanged at 80%. CONCLUSIONS: The original working formulation
produces consistent grading except at grade 2, which is judged to be a misnomer
resulting from Quility effect and other non-rejection phenomena. While acceptable
standardisation can be achieved with the 1990 scheme, the modified scheme has
advantages in that it appears to encourage clear discrimination between
significant and non-significant cardiac rejection. Overall, elimination of grade
2 did not produce an increase in higher grades of cardiac rejection, and thus the
value of this diagnostic grade is questioned.
PMID- 9659188
TI - Comparison of impedance cardiography and dye dilution method for measuring
cardiac output.
AB - OBJECTIVE: To assess the degree of agreement between impedance cardiography,
using the NCCOM3-R7 device, and the gold standard--the dye dilution method--both
under basal conditions and after stimulation of cardiac output. PATIENTS: 35
paired measurements in five healthy male volunteers. INTERVENTIONS: To obtain
higher levels of cardiac output, cardiac performance was stimulated with a
dopamine infusion. RESULTS: In 35 paired measurements, the mean of all the
impedance values was higher than that of the dye dilution values, at 10.2 v 7.4
l/min (p < 0.0001). The mean discrepancy between the two methods was 3.3 l/min,
and the mean bias -2.9 l/min, with limits of agreement of -9.0 and 3.2 l/min. A
change in cardiac output could not adequately be predicted by the NCCOM3-R7. In
20 of 25 measurements obtained during continuous intravenous dopamine infusions
there was a rise in dye dilution cardiac output (range 0.2 to 5.9 l/min). Neither
the magnitude nor the direction of the change in dye dilution values corresponded
with the change measured by impedance cardiography. The mean discrepancy here
between the two methods was 1.8 l/min, and the mean bias -0.8 l/min, with limits
of agreement of -4.9 and 3.3 l/min. CONCLUSIONS: In healthy volunteers, impedance
cardiography with NCCOM3-R7 is inadequate for assessing cardiac output when
compared with the dye dilution method.
PMID- 9659189
TI - Hospital acquired native valve endocarditis: analysis of 22 cases presenting over
11 years.
AB - OBJECTIVE: To analyse hospital acquired infective endocarditis cases with respect
to age, sex, clinical, laboratory, and echocardiographic features,
predisposition, complications, surgery, mortality, and diagnostic criteria.
DESIGN: Prospective cohort study. SETTING: Teaching hospital. PATIENTS: A series
of 200 patients with infective endocarditis presenting over 11 years, 168 with
native valve infective endocarditis, of whom 22 acquired this infection in
hospital. RESULTS: 22 (14%) of the 168 cases of native valve infection were
hospital acquired. The most common pathogens were staphylococci (77%). Two thirds
of patients had no cardiac predisposition; one third had end stage renal disease.
The most common source of infection was vascular access sites (73%). Eleven
patients died. In 11 cases, infective endocarditis was proven pathologically (six
at necropsy, five during surgery) and analysis of these showed that 45% were
classed as probable by the Beth Israel criteria, 73% as definite by the Duke
criteria, and 91% as definite by our suggested modifications of the Duke
criteria. Figures for the 11 cases not proven pathologically were 27%, 73%, and
91%, respectively. Five of the 22 cases (22%) were rejected by the Beth Israel
criteria but none were rejected by the Duke criteria with or without our
modifications. CONCLUSIONS: Hospital acquired infective endocarditis is difficult
to diagnose. The Duke criteria have improved diagnostic sensitivity and our
modifications have improved it further. Mortality is high but has been reduced by
surgery. This serious infection could, in many cases, be prevented by improved
care of intravascular lines and prompt removal when obviously infected.
PMID- 9659190
TI - A prioritisation system for elective coronary angiography.
AB - OBJECTIVE: To devise a clinical prioritisation system for rationing access to a
cardiac catheter waiting list and to describe its performance at predicting
angiographic findings and selecting patients for angioplasty or coronary artery
bypass graft surgery. SETTING: Tertiary level cardiology centre. METHODS: (1) 665
consecutive patients on an elective waiting list for coronary angiography were
scored using a system derived from established clinical criteria for selecting
patients for coronary surgery (New Zealand/Duke). The scores were compared with
clinical outcome (referral for surgery, angioplasty, or medical management). (2)
In a subset of 125 patients, scores derived from clinical criteria and exercise
testing were compared with findings on coronary angiography. (3) Multivariate
analysis was used in a new group of 178 patients to identify factors that would
be better predictors of the angiographic score. (4) A new scoring system was
devised based partly on the results of the multivariate analysis. It was applied
to a new test group of 100 patients using clinical outcome and angiographic score
as outcome measures. RESULTS: (1) Using the established clinical score, similar
proportions of patients were referred after angiography for medical management,
angioplasty, or coronary bypass grafting, irrespective of their original score.
The exceptions were patients with a score < 20, who were more likely to continue
medical management. (2) There was poor correlation (r = 0.05) between the
clinical score and the subsequent angiographic score. (3) Multivariate analysis
identified age, male sex, previous myocardial infarction, high cholesterol, and
diabetes as independent predictors of coronary score. (4) The modified scoring
system, incorporating the predictors identified by multivariate analysis,
performed better than the original scoring system in predicting coronary score
when both were tested, but some patients had severe disease despite a low score.
CONCLUSIONS: Patients can be ranked using clinical and non-invasive criteria, and
a rationing system implemented on this basis. With prioritisation by noninvasive
criteria, the risk of missing serious coronary disease in patients with
relatively mild symptoms must be accepted; this risk becomes greater the more
stringently rationing is applied.
PMID- 9659191
TI - Effects of alpha tocopherol and beta carotene supplements on symptoms,
progression, and prognosis of angina pectoris.
AB - OBJECTIVE: To evaluate the effects of alpha tocopherol and beta carotene
supplements on recurrence and progression of angina symptoms, and incidence of
major coronary events in men with angina pectoris. DESIGN: Placebo controlled
clinical trial. SETTING: The Finnish alpha tocopherol beta carotene cancer
prevention study primarily undertaken to examine the effects of alpha tocopherol
and beta carotene on cancer. SUBJECTS: Male smokers aged 50-69 years who had
angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795).
INTERVENTIONS: alpha tocopherol (vitamin E) 50 mg/day, beta carotene 20 mg/day or
both, or placebo in 2 x 2 factorial design. MAIN OUTCOME MEASURES: Recurrence of
angina pectoris at annual follow up visits when the questionnaire was
readministered; progression from mild to severe angina; incidence of major
coronary events (non-fatal myocardial infarction and fatal coronary heart
disease). RESULTS: There were 2513 recurrences of angina pectoris during follow
up (median 4 years). Compared to placebo, the odds ratios for recurrence in the
active treatment groups were: alpha tocopherol only 1.06 (95% confidence interval
(CI) 0.85 to 1.33), alpha tocopherol and beta carotene 1.02 (0.82 to 1.27), beta
carotene only 1.06 (0.84 to 1.33). There were no significant differences in
progression to severe angina among the groups given supplements or placebo.
Altogether 314 major coronary events were observed during follow up (median 5.5
years) and the risk for them did not differ significantly among the groups given
supplements or placebo. CONCLUSIONS: There was no evidence of beneficial effects
for alpha tocopherol or beta carotene supplements in male smokers with angina
pectoris, indicating no basis for therapeutic or preventive use of these agents
in such patients.
PMID- 9659192
TI - Characterisation of coronary atherosclerotic morphology by spectral analysis of
radiofrequency signal: in vitro intravascular ultrasound study with histological
and radiological validation.
AB - OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency
(RF) signal offers advantages over standard videodensitometric analysis in
identifying the morphology of coronary atherosclerotic plaques. METHODS: 97
regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure
perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at
250 MHz. Two different sizes of ROI were identified from scan converted images,
and relative amplitudes of different frequency components were analysed from raw
data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis
intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth
(17-42 MHz). RF images were constructed and compared with comparative histology
derived from microscopy and radiological techniques in three dimensions. RESULTS:
Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral
slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (
0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for
dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in
heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in
microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in
microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9
(2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power:
moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate
11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose,
moderate, and dense, were discriminated with both y-axis intercept, spectral
slope, and mean power. Lipid could be differentiated from other types of plaque
tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept
from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue,
dense fibrotic tissue, microcalcification, and heavy calcium. No significant
differences in any of the measured parameters were seen between the results
obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis
of unprocessed ultrasound signal may lead to accurate identification of
atherosclerotic plaque morphology.
PMID- 9659193
TI - Abnormal ventricular activation and repolarisation during dobutamine stress
echocardiography in coronary artery disease.
AB - OBJECTIVE: To assess possible ECG changes caused by dobutamine stress and their
relation to wall motion disturbances in patients with coronary artery disease.
DESIGN: Prospective recording and analysis of 12 lead ECG at rest and during each
stage of dobutamine stress echocardiography, and correlation with wall motion
changes. SETTING: A tertiary referral centre for cardiac disease equipped with
non-invasive facilities for pharmacological stress tests. SUBJECTS: 27 patients,
mean (SD) age 60 (8) years, with documented evidence of coronary artery disease
in whom dobutamine stress echo was clinically indicated, and 17 controls of
similar age. RESULTS: In controls, all ECG intervals shortened with increasing
heart rate but in the patient group only PR and QT intervals shortened while QRS
duration broadened and QTc interval prolonged progressively. In the 27 patients,
16 developed chest pain, 15 with reduced left ventricular long axis systolic
excursion (p < 0.001), and all showed reduced peak lengthening rate; ST segment
shift appeared in 16, 13 of whom developed chest pain, but did not correlate with
reduction of either systolic long axis excursion or peak lengthening rate; QRS
duration broadened in 20, 16 with reduction of long axis excursion (p < 0.02)
which was more often seen at the septum (p < 0.005); QTc interval prolonged in
19, all of whom had associated reduction of peak long axis lengthening rate (p <
0.02). CONCLUSIONS: QRS duration and QTc interval both normally shorten with
dobutamine stress, while in coronary artery disease they both lengthen: changes
in QRS duration correlate with systolic and QTc interval with diastolic left
ventricular wall motion disturbances. ST segment shift also occurred in most
patients, but without consistent correlation with wall motion abnormalities. It
was thus less discriminating than the other two abnormalities in this respect.
PMID- 9659194
TI - Enhanced dispersion of epicardial activation-recovery intervals at sites of
histological inhomogeneity during regional cardiac ischaemia and reperfusion.
AB - OBJECTIVE: To examine how epicardial activation and repolarisation patterns
change in the course of ischaemia, and how these changes are related to the
underlying histological structures. METHODS: Langendorff perfused isolated rabbit
hearts were submitted to 30 minutes of left anterior descending coronary artery
occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was
plotted during the various experimental phases. Activation time points were
determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From
these data the local activation-recovery interval (ARI), its dispersion (SD of
ARI), and the geometry of the activation spread could be analysed. After the
experiments the hearts were processed histologically and the mapping data were
projected onto histological slides. RESULTS: There was elevation of the ST
segment within the occluded area, which recovered during reperfusion. Within this
area, ARI was significantly shortened and its dispersion was maximally enhanced.
The enhancement of dispersion was pronounced at sites of histological
inhomogeneity like fat, connective tissue, or vessels. There was also a change in
the preferential direction of activation spread within the occluded zone with a
marked transverse propagation of the activation wave-front, whereas under normal
conditions the activation followed the longitudinal fibre axis. In addition, the
total activation time in the occluded area was significantly prolonged.
CONCLUSIONS: Ischaemia alters the local activation pattern with enhanced
dispersion, especially at sites of histological irregularity, transverse shift of
the activation waves, and a general slowing of conduction, which may explain the
increased susceptibility to arrhythmia in hearts with enhanced histological
irregularities--for example, an infarct or in multi-infarcted hearts, or after
myocarditis.
PMID- 9659195
TI - Does restrictive right ventricular physiology in the early postoperative period
predict subsequent right ventricular restriction after repair of tetralogy of
Fallot?
AB - OBJECTIVE: To assess the relation between immediate postoperative right
ventricular (RV) diastolic physiology and subsequent diastolic function in
patients after repair of tetralogy of Fallot. DESIGN: Serial prospective
echocardiographic study early after surgical repair of tetralogy of Fallot and at
mid-term follow up. SETTING: Tertiary referral centre. PATIENTS: 34 patients who
had repair of tetralogy of Fallot between 1992 and 1995 were studied. MAIN
OUTCOME MEASURES: Restrictive RV physiology defined as antegrade flow in the
pulmonary artery in late diastole throughout the respiratory cycle. RESULTS:
Sixteen of the 34 patients had early restrictive RV physiology. The need for
transannular patch repair was an independent variable predictive of early
restriction (odds ratio 4.3 (1.1-47), p < 0.05). Nine of 16 patients with early
restriction also had restriction at follow up, while 15 of 16 patients without
restrictive RV physiology continued without restriction. Early restriction was
the only independent variable predictive of late restriction (odds ratio 6.0 (1.9
273), p = 0.01). CONCLUSIONS: Early and mid-term restrictive RV physiology after
repair of tetralogy of Fallot is related to the repair type. Although evidence
for this physiology tends to resolve in the first few days after operation, it is
highly predictive of subsequent abnormalities of RV diastolic function.
Similarly, normal RV diastolic physiology without restriction in the immediate
postoperative period persists in the mid-term and may be associated with the long
term problems of progressive RV dilatation.
PMID- 9659197
TI - Neck pounding during sinus rhythm: a new clinical manifestation of dual
atrioventricular nodal pathways.
AB - OBJECTIVE: To determine the clinical and electrophysiological characteristics of
patients with paroxysmal palpitations and neck pounding during sinus rhythm.
METHODS: Clinical, electrocardiographic, and electrophysiological characteristics
of six patients with paroxysmal palpitations and neck pounding during sinus
rhythm were studied in basal conditions and when symptomatic. Response to
treatment was observed. RESULTS: Baseline ECGs were normal (four patients) or had
first degree atrioventricular block with intermittent PR shortening. During
symptoms, narrow QRS rhythms were seen without visible P waves (three patients)
or with P waves partially hidden in the QRS complex (three patients). Dual
atrioventricular nodal pathways were found in all five patients who had
electrophysiological studies. In these patients the slow pathway conduction time
was long enough (mean (SD), 425 (121) ms) for ventricular activation after slow
pathway conduction during sinus rhythm to coincide with the next atrial
depolarisation, causing neck pounding during exercise (four patients) or at rest
(two patients). Tachycardia was not induced in any patient. Medical treatment
aggravated symptoms in three patients. A pacemaker was successfully used in two.
CONCLUSIONS: Neck pounding during sinus rhythm is a clinical manifestation of
dual atrioventricular nodal pathways. Medical treatment may aggravate symptoms
but a pacemaker may offer definitive relief.
PMID- 9659196
TI - Haemodynamic patterns in patients with scorpion envenomation.
AB - OBJECTIVE: To study cardiovascular haemodynamics following scorpion envenomation.
SETTING: Intensive care unit of a university hospital. PATIENTS: Eight patients
with Indian red scorpion (Mesobuthus tamulus) stings. INTERVENTION: Captopril
(6.25 to 12.5 mg orally) every 30 minutes until pulmonary oedema resolved. MAIN
OUTCOME MEASURES: Haemodynamic data obtained by pulmonary artery catheterisation.
RESULTS: Two haemodynamic patterns were seen. There was a predominant vascular
effect in one patient, with severe hypertension, tachycardia, increased systemic
vascular resistance index (SVRI = 5893 dyn.s.cm-5), and normal cardiac index
(2.73 l/m2). A predominant myocardial effect with left ventricular dysfunction
and normal right ventricular function was seen in the other seven patients, with
tachycardia, pulmonary oedema, mild hypotension, reduced stroke volume (mean
(SD), 25.9 (8.3) ml/m2), normal SVRI (1812 (831) dyn.s.cm-5), and increased
pulmonary artery wedge pressure (PAWP = 25 (4.4) mm Hg). Following mild
dehydration pulmonary oedema subsided (PAWP = 14 (8.5) mm Hg) in three of these
patients, but hypovolaemic shock developed (right atrial pressure (RAP) = 1.3
(2.1) mm Hg); pulmonary oedema recurred with rehydration. One patient developed
fatal cardiogenic shock with raised PAWP (27 mm Hg) and RAP (11 mm Hg), and
vasodilatation (SVRI = 1129 dyn.s.cm-5). Stroke volume (30.5 (8.7) ml/m2) and
cardiac output (4.3 (1.5) 1/m2) improved with resolution of pulmonary oedema
(PAWP = 14.4 (4.2) mm Hg) following afterload reduction with captopril.
CONCLUSIONS: Mild envenomation causes severe vasoconstriction and hypertension.
Severe envenomation produces predominant left ventricular dysfunction with normal
systemic vascular resistance manifesting as pulmonary oedema or severe
hypotension depending on the fluid balance. Shock due to biventricular
dysfunction and vasodilatation occurs terminally.
PMID- 9659198
TI - Circadian rhythm of the signal averaged electrocardiogram and its relation to
heart rate variability in healthy subjects.
AB - OBJECTIVE: To examine the circadian variation in the signal averaged
electrocardiogram (saECG) and heart rate variability and investigate their
relations in healthy subjects. METHODS: 24 hour ECGs were obtained with a three
channel recorder using bipolar X, Y, and Z leads in 20 healthy subjects. The
following variables were determined hourly: heart rate, filtered QRS (f-QRS)
duration, low and high frequency components of heart rate variability (LF and
HF), and the LF/HF ratio. RESULTS: Heart rate, f-QRS duration, HF, and the LF/HF
ratio showed significant circadian rhythms, as determined by the single cosinor
method. Heart rate and the LF/HF ratio increased during daytime, and f-QRS
duration and HF increased at night. f-QRS duration was negatively correlated with
heart rate (r = 0.95, p < 0.001) and the LF/HF ratio (r = 0.94, p < 0.001) and
positively with HF (r = 0.93, p < 0.001). CONCLUSIONS: f-QRS duration has a
significant circadian rhythm in healthy subjects and is closely related to the
circadian rhythm of autonomic tone.
PMID- 9659199
TI - Distribution of fast heart rate episodes during paroxysmal atrial fibrillation.
AB - OBJECTIVE: To investigate the defibrillator waiting time (time between the
recognition of atrial fibrillation and the actual shock) by studying paroxysmal
atrial fibrillation episodes with RR intervals shorter than a certain limit (that
is, episodes during which defibrillation should not be attempted). METHODS: Long
term 24 hour Holter recordings from a digoxin v placebo crossover study in
patients with paroxysmal atrial fibrillation were analysed. In all, 23 recordings
with atrial fibrillation episodes of at least 1000 ventricular cycles and with <
20% Holter artefacts or noise were used (11 recorded on placebo and 12 on
digoxin). For each recording, the mean ("mean waiting time") and maximum
("maximum waiting time") duration of continuous sections of atrial fibrillation
episodes with all RR intervals shorter than a certain threshold were evaluated,
ranging the threshold from 400 to 1000 ms in 10 ms steps. For each threshold, the
mean and maximum waiting times were compared between recordings on placebo and on
digoxin. RESULTS: Both the mean and maximum waiting times increased exponentially
with increasing threshold. Practically acceptable mean waiting times less than
one minute were observed with thresholds below 600 ms. There were no significant
differences in mean waiting times and maximum waiting times between recordings on
placebo and digoxin, and only a trend towards shorter waiting times on digoxin.
CONCLUSIONS: Introduction of a minimum RR interval threshold required to deliver
atrial defibrillation leads to practically acceptable delays between atrial
fibrillation recognition and the actual shock. These delays are not prolonged by
digoxin treatment.
PMID- 9659200
TI - Pseudoaneurysm of femoral artery after catheterisation: treatment by a mechanical
compression device guided by colour Doppler ultrasound.
AB - BACKGROUND: Femoral artery pseudoaneurysm is a significant complication in
patients undergoing diagnostic or therapeutic catheterisation. First choice
treatment for pseudoaneurysm is freehand ultrasound guided compression repair,
which is time consuming and uncomfortable for the patient and operator. AIM: To
explore a mechanical compression device (FemoStop) as an alternative treatment
for iatrogenic femoral artery pseudoaneurysm. METHODS: Fourteen patients with
pseudoaneurysm were considered for treatment with FemoStop after a brief freehand
ultrasound guided compression repair to confirm the compressibility of the
lesion. The FemoStop compression was applied for 20 minutes. The result was
controlled with colour Doppler ultrasound, and a second cycle of 20 minutes
followed if necessary. RESULTS: FemoStop compression was successful in 13 of the
14 patients. The mean compression time was 33 minutes (range, 20-60). The mean
number of compression periods was 1.6 (range 1-3). FemoStop compression was
successful in all 11 patients not taking anticoagulants and in two of three
patients receiving anticoagulants. The mean compression time in patients given
oral or intravenous anticoagulants was longer (50 v 27 minutes). Colour Doppler
ultrasound 12 hours after the procedure indicated no recurrence of pseudoaneurysm
in the 13 patients with initial success. CONCLUSIONS: FemoStop compression for
iatrogenic pseudoaneurysm is feasible, and as safe and effective as freehand
ultrasound guided compression repair. It is more comfortable for the patient and
operator, and probably more economical than freehand compression.
PMID- 9659201
TI - Aneurysms and pseudoaneurysms of saphenous vein coronary artery bypass grafts.
AB - Aneurysms of saphenous vein grafts to coronary arteries are unusual complications
of coronary artery bypass graft (CABG) surgery. Three patients (men aged 47, 62,
and 68 years) are presented with spontaneous chest pains 10, 21, and 17 years
after CABG surgery. In one case, the saphenous vein graft had eroded into the
right atrium and had established a fistula between the graft and the right
atrium. Diagnosis of saphenous vein graft aneurysms was confirmed by
echocardiography, computed tomography or magnetic resonance imaging, and by
arteriography. Two patients were treated surgically, the third by percutaneous
coil embolisation followed by balloon angioplasty of the right coronary artery.
PMID- 9659202
TI - Reopening of persistent left superior caval vein after bidirectional
cavopulmonary connections.
AB - Persistent left superior vena cava (SVC) is a not uncommon finding in patients
with congenital heart disease. This anatomical variant must be recognised before
doing a Glenn anastomosis, bidirectional cavopulmonary connection or a Fontan
type procedure. Following these procedures, reopening of a left SVC leading to
clinical cyanosis can occur. Five cases are described in whom persisting left
SVCs were excluded before performing a bidirectional cavopulmonary connection or
Fontan procedure but (re-)opened after surgery, leading to cyanosis either by
reducing effective pulmonary blood flow (bidirectional cavopulmonary connection)
or by an obligatory right to left shunt (Fontan). These observations suggest
that, embryologically, the lumen of the left SVC obliterates rather than
disappears. Balloon occlusion angiography of the innominate vein before
cavopulmonary connections or Fontan procedures might improve detection of these
collateral vessels.
PMID- 9659203
TI - Truncus arteriosus with anterior origin of a hypoplastic main pulmonary artery.
AB - A newborn with an unusual form of truncus arteriosus is described, whose clinical
presentation and certain features of her anatomy were more typical of pulmonary
atresia with a ventricular septal defect. The morphological differentiation of
certain types of truncus arteriosus and pulmonary atresia with ventricular septal
defect remains an area of speculation among cardiac pathologists, and research in
this area is being done using animal models. The anatomic features of the heart
described in this report may assist in this discussion as the application of
observations made in animal models to human cardiac development may be
problematic.
PMID- 9659204
TI - Images in cardiology. An isolated single coronary artery.
PMID- 9659205
TI - Cavernous haemangioma in the coronary sinus.
AB - A 58 year old man with a history of cerebral infarction was admitted to hospital
with chest discomfort and dyspnoea. He had no history of precordial chest
discomfort. Angiography and left ventriculography showed that coronary fistulas
connected the coronary sinus with the left circumflex and right coronary
arteries. His coronary sinus did not communicate with the right atrium, draining
instead into a persistent left superior vena cava. Angiography showed a mass,
suspected to be a thrombus, in the coronary sinus. Transoesophageal
echocardiography confirmed the presence of a mass in the atrioventricular groove.
The mass was removed at surgery and proved to be a cavernous haemangioma.
PMID- 9659206
TI - Sotalol associated polymorphic ventricular tachycardia and coronary spasm.
AB - Sotalol may induce torsade de pointes through cardiac action potential
prolongation, but a proarrhythmic effect secondary to its beta blocking action
has not been reported. A 54 year old man presented with symptoms of angina and
presyncope, subsequently demonstrated to be associated with coronary spasm.
Treatment with sotalol exacerbated his symptoms and resulted in recurrent
polymorphic ventricular tachycardia with a pattern indistinguishable from that
caused by a class III action. Following sotalol with-drawal polymorphic
ventricular tachycardia resolved completely. Polymorphic ventricular tachycardia
in patients treated with sotalol may therefore not always be the result of
delayed repolarisation, but may be caused by beta adrenoceptor blockade.
PMID- 9659207
TI - Anomalous left pulmonary artery without pulmonary artery sling.
PMID- 9659208
TI - Atrioventricular fistula: an unusual complication of a ventricular pseudoaneurysm
after myocardial infarction.
PMID- 9659209
TI - An unusual intracardiac shunt secondary to penetrating cardiac trauma.
PMID- 9659210
TI - Cardiogenic refractory hypoxaemia secondary to blunt chest trauma: diagnosis by
transoesophageal echocardiography.
PMID- 9659211
TI - Images in cardiology. Primary angioplasty and stenting of left main coronary
occlusion.
PMID- 9659212
TI - Human stress cardiomyopathy mimicking acute myocardial syndrome.
PMID- 9659213
TI - Effect of atrioventricular asynchrony on platelet activation.
PMID- 9659214
TI - Lymphocyte trafficking: CD4 T cells with a 'memory' phenotype (CD45RC-) freely
cross lymph node high endothelial venules in vivo.
AB - Antigen encounter not only induces a change in surface expression of CD45RC
isoforms in the rat from a high (CD45RC+) to a low molecular weight molecule
(CD45RC-), but also stimulates changes in expression of adhesion molecules that
regulate CD4 T-cell migration. T cells with an activated or 'memory' phenotype
(CD45RC-) are thought to enter lymph nodes almost exclusively via afferent
lymphatics whereas T cells in a resting state (CD45RC+) migrate across high
endothelial venules (HEV). The present study monitored the rapid recirculation
from blood to lymph of allotype-marked CD45RC T-cell subsets. Surprisingly, we
found that CD45RC- CD4 T cells entered the thoracic duct slightly faster and
reached peak numbers 3 hr earlier (18 hr) than did the CD45RC+ subset. To
determine whether the entrance of CD45RC+ and RC- subsets was restricted to HEV
and afferent lymphatics, respectively, recirculation of CD4 T cells was monitored
in mesenteric lymphadenectomized (MLNx) rats (on healing the intestinal afferent
lymphatics are joined directly to the thoracic duct), or in recipients that had
had the mesenteric lymph node (MLN) acutely (2-3 hr) deafferentized (entry would
be restricted to HEV). In these studies CD45RC- CD4 T cells entered the MLN
across HEV on an equal basis with T cells expressing a CD45RC+ phenotype.
Contrary to currently held dogma the results showed that, in vivo, CD4 T cells
with a memory phenotype freely enter lymph nodes (LN) across HEV as well as via
afferent lymphatics.
PMID- 9659216
TI - Injection of T-cell receptor peptide reduces immunosenescence in aged C57BL/6
mice.
AB - Previous studies established that retrovirally infected young mice produced large
amounts of autoantibodies to certain T-cell receptor (TCR) peptides whose
administration diminished retrovirus-induced immune abnormalities. C57BL/6 young
(4 weeks) and old (16 months) female mice were injected with these same synthetic
human TCR V beta 8.1 or 5.2 peptides. Administration of these autoantigenic
peptides to old mice prevent immunosenescence, such as age-related reduction in
splenocyte proliferation and interleukin-2 (IL-2) secretion. TCR V beta peptide
injection into young mice had no effect on T- or B-cell mitogenesis and IL-4
production while modifying tumour necrosis factor-alpha (TNF-alpha), IL-6, and
interferon-gamma (IFN-gamma) secreted by mitogen-stimulated spleen cells. TCR V
beta injection also retarded the excessive production of IL-4, IL-6 and TNF-alpha
induced by ageing. These data suggest that immune dysfunction and abnormal
cytokine production, induced by the ageing process, were largely prevented by
injection of selected TCR V beta CDR1 peptides.
PMID- 9659215
TI - Protein kinase C mediates the signal for interferon-gamma mRNA expression in
cytotoxic T cells after their adhesion to laminin.
AB - A cytotoxic T-cell line, CTLL-2 cells, showed spreading after adhering to
extracellular matrix proteins such as fibronectin (FN), laminin (LN) and
hyarulonic acid (HA). The adhesion of CTLL-2 cells to LN was mediated by very
late activation antigen-6 (VLA-6). Expression of interferon-gamma (IFN-gamma)
mRNA was enhanced in CTLL-2 cells, also when they adhered to extracellular matrix
proteins; and the enhanced IFN-gamma mRNA expression by adhering to LN was
blocked by anti-alpha 6 antibody. Calphostin C, a protein kinase C (PKC)
inhibitor, markedly inhibited the enhancement of IFN-gamma mRNA expression in a
dose-dependent manner, which suggested that PKC acted as a second messenger in
the IFN-gamma mRNA expression mediated by the interaction of VLA-6 with LN in
CTLL-2 cells. Furthermore, confocal laser-microscopic analysis and Western blot
analysis revealed that PKC-alpha was activated after CTLL-2 cells adhered to LN.
PKC activity translocated from the cytosol fraction to the particulate fraction,
after CTLL-2 cells adhered to LN. Altogether, we suggest that PKC plays an
important role in the signal transduction for IFN-gamma mRNA expression after
cytotoxic T cells adhere to LN.
PMID- 9659217
TI - Cross-talk between V beta 8+ and gamma delta+ T lymphocytes in contact
sensitivity.
AB - We have previously reported that T lymphocytes proliferating in vitro to the
hapten trinitrochlorobenzene (TNCB) exhibit a very restricted V beta gene usage
and response to TNCB is limited to T-cell receptors (TCR) composed of V beta 8.2
in combination with V alpha 3.2, V alpha 8 and V alpha 10. This paper
investigates the role played by T lymphocytes expressing the V beta 8.2 gene
segment in the contact sensitivity (CS) reaction to TNCB in the intact mouse and
in its passive transfer into naive recipient mice. Mice injected with monoclonal
antibodies to V beta 8 are unable to develop CS upon immunization with TNCB and 4
day TNCB-immune lymph node cells from mice that had been depleted in vivo or in
vitro of V beta 8+ T lymphocytes fail to transfer CS. However, when separated V
beta 8+ and V beta 8- cells were used for passive transfer, it was found that V
beta 8+ T lymphocytes failed to transfer CS when given alone to recipient mice
and a V beta 8- population was absolutely required. Further analysis revealed
that within the V beta 8- population, T lymphocytes expressing the gamma delta
TCR were fundamental to allow transfer of the CS reaction. These gamma delta
cells were found to be antigen non-specific, genetically unrestricted and to
rearrange the V gamma 3 gene segment. This indicates that transfer of the CS
reaction requires cross-talk between V beta 8+ and gamma delta+ T lymphocytes,
thus confirming our previous results obtained using TNCB-specific T-cell lines.
Time-course experiments showed that V beta 8+ lymphocytes taken 4-24 days after
immunization with TNCB were able to proliferate and produce interleukin-2 (IL-2)
in response to the specific antigen in vitro. Similar time-course experiments
were then undertaken using the passive transfer of the CS reaction system. The
results obtained confirm that TNCB-specific V beta 8+ T lymphocytes are present
in the lymph nodes of immunized mice from day 4 to day 24, and reveal that gamma
delta+ T lymphocytes are active for a very short period of time, i.e. days 4 and
5 after immunization. In fact, TNCB-specific V beta 8+ cells are able to transfer
CS when taken 4-24 days after immunization, providing the accompanying V beta 8-
or gamma delta+ T lymphocyte are obtained 4 days after immunization. In contrast,
injection of V beta 8+ T lymphocytes together with V beta 8- or gamma delta+ T
lymphocytes that had been taken 2 or 6 days after immunization, failed to
transfer significant CS into recipient mice. Taken together, our results confirm
that cross-talk between V beta 8+ and gamma delta+ T lymphocytes is necessary for
full development of the CS reaction and may explain why the CS reaction in the
intact mouse lasts up to 21 days after immunization while the ability of immune
lymph node cells to transfer CS is limited to days 4 and 5 after immunization.
PMID- 9659218
TI - Investigation of the role of delayed-type-hypersensitivity responses to myelin in
the pathogenesis of Theiler's virus-induced demyelinating disease.
AB - The contribution of autoimmune responses to the pathogenesis of Theiler's virus
induced demyelinating disease was investigated. Delayed-type hypersensitivity
responses to myelin were examined in both symptomatic and asymptomatic mice at
different times post-infection, in order to determine whether autoreactivity
correlates with the development of demyelination. The results indicate that
although autoimmune responses probably do not play a major role in the initiation
of demyelination at early times post-infection, autoreactivity to myelin antigens
dose eventually develop in symptomatic animals, perhaps through the mechanism of
epitope spreading. Autoimmunity to myelin components is therefore an additional
factor that may contribute to lesion progression in chronically diseased animals.
PMID- 9659219
TI - Active suppression induced by cutaneous exposure to bacterial superantigen is
prevented by interleukin-12 treatment in vivo.
AB - Exposure to the bacterial superantigen staphylococcal enterotoxin B (SEB) leads
to inhibition of several immune responses and the induction of regulatory cells.
The aim of this study was to characterize these regulatory cells further and to
investigate the effect of interleukin-12 (IL-12) on superantigen-induced
suppression. For this purpose BALB/c mice were injected subcutaneously with low
doses of SEB that did not deplete the SEB-reactive V beta T cells. Intravenous
transfer of unseparated local-draining lymph node cells from these SEB-treated
animals suppressed the proliferative response of mononuclear spleen cells of
naive syngeneic recipients for at least 3 weeks. The regulatory cells did not
produce the type 2 cytokines, interleukin-4 (IL-4) or interleukin-10 (IL-10), or
increased amounts of transforming growth factor-beta (TGF-beta). Depletion of
CD8+ or SEB-reactive V beta 7+ and V beta 8+ T cells, prior to transfer,
abrogated the suppressive effect. Intraperitoneal injections of IL-12 into
donors, prior to SEB treatment, prevented the induction of functional regulatory
cells, and treatment of recipients with IL-12, prior to receipt of cells from SEB
treated donors, prevented the suppressive effect of regulatory cells that were
already induced. The data indicate that exposure to minute amounts of
superantigens directly induces superantigen-reactive and CD8+ regulatory T cells
and that superantigen-induced suppression can be prevented and reversed by IL-12
treatment in vivo.
PMID- 9659220
TI - Effect of T-helper cytokine environment on specificity of T-cell responses to
mycobacterial 65,000 MW heat-shock protein.
AB - The purpose of this work was to determine if the fine specificity of T cells
differed between mice immunized with an antigen in a T helper 1 (Th1) cytokine
dominated environment as compared with a T helper 2 (Th2) cytokine-dominated
environment. It was found that splenic T cells from mice immunized with
mycobacterial heat-shock protein (hsp 65) and interleukin-12 (IL-12) produced
less interleukin-4 (IL-4) and more interferon-gamma (IFN-gamma) in response to
stimulation with hsp 65 in vitro than did T cells from mice immunized with hsp 65
alone. The T-cell proliferative response to hsp 65 did not differ between the two
groups of mice, although the responses were higher than those of T cells from non
immunized mice. Strikingly, T cells from mice given hsp 65 and IL-12 gave
significantly higher responses to six peptides (corresponding to the sequence of
hsp 65) to which T cells from mice immunized with hsp 65 alone did not respond.
It is considered that different epitopes are presented to T cells (possibly owing
to changes in antigen processing) if the environment is shifted, by IL-12, from
Th2 towards Th1 cytokines.
PMID- 9659221
TI - Regulation of interleukin-6 and interleukin-6R alpha (gp80) expression by murine
immunoglobulin-secreting B-cell hybridomas.
AB - We have examined the contribution of endogenous interleukin-6 (IL-6) to the
differentiation of murine B-cell hybridomas. AT73 was established by somatic
hybridization between BALB/c mice B cells and 2.52M, a hypoxanthine-aminopterine
thymidine (HAT) medium-sensitive B-cell line mutant. It spontaneously secreted
IgM, and addition of exogenous IL-6 augmented IgM secretion. Triggering of CD40
led to an augmentation of IL-6 expression and IgM secretion. Blocking the binding
of IL-6 to its cellular receptor through the use of inhibitory monoclonal
antibodies inhibited CD40-induced IgM secretion, suggesting a possible autocrine
role of IL-6 for the differentiation of a CD40-activated B-cell hybridoma. Co
triggering with CD40 and B-cell receptor or activation through CD40 and IL-4 led
to a synergistic augmentation of IL-6 expression as well as additive IgM
secretion; this was followed by a marked decrease in the expression of B-cell
surface markers on the cell membrane. Furthermore, under conditions where IL-6
expression was augmented, gp80 expression was down-regulated, suggesting a
negative feedback mechanism in this B-cell hybridoma. These findings provide a
role by which T-cell-dependent activation through CD40 regulates an IL-6
autocrine loop, controlling B-cell differentiation.
PMID- 9659222
TI - Multiple signals regulate the intracellular trafficking of HLA-DM in B
lymphoblastoid cells.
AB - Peptide loading by major histocompatibility complex (MHC) class II molecules
occurs in the endocytic pathway and is critically dependent upon the function of
the class II-related molecule human leucocyte antigen-DM (HLA-DM). We have
previously shown that a tyrosine-based lysosomal targeting signal present in the
cytoplasmic tail of DMB has the capacity to target HLA-DM to peptide-loading
compartments in HeLa cells. Here we investigate the importance of this signal in
directing HLA-DM to processing compartments in professional antigen-presenting
cells. We reconstituted a DMB-negative B-lymphoblastoid cell line with native or
targeting-deficient DMB and show that in the absence of its tyrosine signal, DMB
Y230A is as efficient as the wild-type molecule in inducing MHC class II SDS
stable dimer formation; restoring expression of the conformation-dependent DR3
epitope 16:23; the removal of CLIP; and accessing lysosomal peptide-loading
compartments. By transient transfection in HeLa cells we show that Ii is able to
compensate for loss of DMB-encoded targeting information. These data imply that
in cells expressing physiological levels of class II, Ii and DM, there is
sufficient association with Ii to direct the majority of DM into the endocytic
pathway. Thus MHC class II and HLA-DM may follow similar intracellular
trafficking pathways on route to antigen-processing compartments.
PMID- 9659223
TI - Differential cytokine regulation of natural killer cell-mediated necrotic and
apoptotic cytotoxicity.
AB - Natural killer (NK) cells can kill target cells by either necrotic or apoptotic
mechanisms. Using the 51Cr-release assay to measure necrotic death of target
cells, neonatal NK cells had low NK activity (K562 targets) and high lymphokine
activated killer (LAK) activity (Daudi targets) compared with adult cells, as has
been previously reported. Using a 125I-deoxyuridine (125I-UdR) release assay,
cord cells were shown to also have higher apoptotic LAK activity against YAC-1
target cells. Interleukin-4 (IL-4) inhibited interleukin-2 (IL-2)-induced
necrotic killing of target cells by adult effectors but had no such inhibitory
effect on cord cells. In contrast, IL-4 inhibited both adult and cord LAK
cytotoxicity of YAC-1 target cells by apoptotic mechanisms with higher
suppression observed in cord cell preparations. Using a colorimetric substrate
conversion assay, IL-2 induced higher, and IL-4 had a more significant
suppressive effect on, cord cell granzyme B enzyme activity compared with adult
cells, paralleling apoptosis cytotoxicity data. Co-culture of either adult or
cord LAK cells with IL-4 had a similar inhibitory effect on granzyme B protein
expression, as detected by Western blotting. In contrast, IL-4 did not inhibit
perforin expression, thereby defining IL-4 as a cytokine that can differentially
regulate the NK cell-mediated cytotoxicity processes of apoptosis and necrosis.
The differential sensitivity of cord cells to cytokine regulation of cytotoxicity
may also have implications for cord blood transplantations, as NK cells are known
to function as an effector cell in both graft-versus-host disease and in the
graft-versus-leukaemia phenomena.
PMID- 9659224
TI - Interleukin-4 and interleukin-10 are chondroprotective and decrease mononuclear
cell recruitment in human rheumatoid synovium in vivo.
AB - We used the severe combined immunodeficient (SCID) mouse model to assess the
effect of interleukin-4 (IL-4) or IL-10 injection on cartilage degradation and
mononuclear cell (MNC) recruitment to human rheumatoid synovium in vivo. Human
rheumatoid synovium and cartilage from five rheumatoid arthritis patients,
obtained after joint replacement surgery, were engrafted subcutaneously to 6-8
week-old SCID CB17 mice. Synovial tissues were injected with recombinant human IL
4 (rhIL-4, 100 ng; rhIL-10, 100 ng), both cytokines, or tumour necrosis factor
alpha (TNF-alpha) (1000 U), or phosphate-buffered saline twice a week for 4
weeks. The graft was removed and immunochemical analysis was carried out to
assess intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
molecule-1 (VCAM-1) and E-selectin expression. Moreover, cartilage degradation
was assessed through the quantification of the erosion surface on a computerized
image of the engrafted cartilage at high power view. MNC recruitment in the
synovial tissue was determined by labelling blood MNC with indium-111 before
their intraperitoneal injection. The activity obtained in the region of the graft
were determined with a gamma camera 72 hr postinjection. The results are
expressed as a percentage of initial injected activity. After 4 weeks we observed
a decrease of cartilage area in controls (77 +/- 8%), inhibited after injection
of IL-4, IL-10, or both cytokines (90 +/- 3%, 89.1 +/- 4%, 89.2 +/- 5%
respectively), and 57 +/- 17% after TNF-alpha injection. The % MNC activity in
the graft decreased to 77 +/- 81% (NS), 9 +/- 4% (P < 0.003) and 19 +/- 6% (P <
0.007) compared with untreated synovial tissue after treatment with IL-4, IL-10,
or both cytokines, respectively. Moreover, IL-10 but not IL-4 decreased the
expression of ICAM-1 but not VCAM-1 or E-selectin by synovial cells. These
results suggest that IL-10 and IL-4 could have chondroprotective properties, and
that IL-10 but not IL-4 inhibits MNC traffic towards the synovial tissue
efficiently.
PMID- 9659226
TI - Rat mucosal mast cells: the cultured bone marrow-derived mast cell is
biochemically and functionally analogous to its counterpart in vivo.
AB - Mast cells (MC) are biochemically and functionally heterogeneous and the mixture
of MC phenotypes varies according to anatomical location. Intestinal mucosal MC
(IMMC) have been used to study the mucosal MC subset in the rat, but they are
difficult to isolate in sufficient numbers and with consistent purity and
viability. Bone marrow-derived MC (BMMC), with an apparent mucosal MC phenotype,
can be cultured in large numbers and with high purity from normal rat bone marrow
using supernatants from mesenteric lymph node cells of rats infected with the
nematode, Nippostrongylus brasiliensis. We have compared serine proteinase
content, tumour necrosis factor-alpha (TNF-alpha) storage and secretion, and TNF
alpha-dependent cytotoxicity of IMMC and BMMC to assess the appropriateness of
BMMC as in vitro models of mucosal MC. Two-dimensional gel electrophoretic
analysis revealed that the overall protein constituents of BMMC and IMMC were
highly homologous. Immunoblotting confirmed that both MC types expressed the MMC
associated enzyme, rat mast cell proteinase-2 (RMCP-2), but not RMCP-1, mast cell
proteinase-5 (MCP-5) or carboxypeptidase A (CPA), which characterize the
connective tissue MC in the rat and which were detected in a representative of
this subset, namely, the periotoneal MC (PMC). BMMC demonstrated levels of TNF
alpha-dependent cytotoxicity that were equivalent to those of IMMC. Like IMMC,
BMMC contained little stored TNF-alpha, in comparison with PMC, but both MC types
generated substantial amounts of TNF-alpha 6 hr following IgE-mediated
activation. Pretreatment of PMC with recombinant rat interferon-gamma (IFN-gamma)
for 20 hr inhibited anti-immunoglobulin E (anti-IgE)-mediated release of the
granule-associated enzyme, beta-hexosaminidase, whereas identically treated BMMC
were unresponsive to this cytokine. Similar results have previously been reported
for IMMC. Rat BMMC, unlike their more immature and less phenotypically committed
counterparts in the mouse, appear therefore to be more appropriate models for
studies on the mucosal MC.
PMID- 9659225
TI - Peritoneal macrophages play an important role in eliminating human cells from
severe combined immunodeficient mice transplanted with human peripheral blood
lymphocytes.
AB - To elucidate the mechanism of human cell elimination from severe combined
immunodeficient (SCID) mice transplanted with human peripheral blood lymphocytes
(hu-PBL-SCID mice), we explored the immunocytes in the peritoneal cavity in SCID
mice where human PBL were transferred. When the phenotype of peritoneal exudate
cells (PEC) was compared by flow cytometry among three congenic strains of SCID
mice that differ in their acceptability for human PBL, the PEC in NOD-scid mice,
which exhibit the highest acceptability, contained the smallest number of
F4/80lo/-Mac-1(+)-activated macrophages. Moreover, the proportions of natural
killer cells in PEC of the three strains of SCID mice were not always correlated
with the acceptability. These findings suggest the possibility that peritoneal
macrophages eliminate human cells in hu-PBL-SCID mice. To verify this hypothesis,
we evaluated the engraftment of human PBL into SCID mice that were treated with
liposome-encapsulated dichloromethylene diphosphonate, which selectively depletes
macrophages by inducing apoptosis, or 8-aminoguanidine hemisulphate salt, an
inhibitor of inducible nitric oxide synthase of macrophages. As a result, both of
these regimens improved engraftment of human PBL, indicating that peritoneal
macrophages take part in human cell elimination in the peritoneal cavity of hu
PBL-SCID mice and that it is mediated, at least in part, by direct macrophage
cytotoxicity utilizing nitric oxide.
PMID- 9659227
TI - Lactic dehydrogenase virus infection enhances parasite egg production and
inhibits eosinophil and mast cell responses in mice infected with the nematode
Nippostrongylus brasiliensis.
AB - The effects of lactic dehydrogenase virus (LDV) infection on the protective
immune responses to the nematode Nippostrongylus brasiliensis were studied. Mice
with chronic LDV infection showed significantly higher levels of parasite egg
production than non-LDV-infected (control) mice after N. brasiliensis infection.
Concurrent LDV infection also suppressed peripheral blood eosinophilia and the
lung mastocytosis induced by this nematode. LDV infection showed higher
expression levels of the interferon-gamma (IFN-gamma) mRNA in lymph nodes
compared with control mice before N. brasiliensis infection. In addition, the
IgG2a production in LDV-infected mice was higher than that in control mice before
and after N. brasiliensis infection. These results suggest that LDV infection
modulates protective immune responses against N. brasiliensis infection by the
activation of T-helper type 1 cells.
PMID- 9659228
TI - Post-translational modification and intracellular localization of a splice
product of CD46 cloned from human testis: role of the intracellular domains in O
glycosylation.
AB - We obtained a unique CD46 cDNA, STc/CY4, from the human testis, the predicted
amino acid sequence of which suggested the presence of a novel isoform of CD46.
This message was present predominantly in the testis, and the predicted isoform
possessed a short (11 amino acids) transmembrane section (TM) and an unidentified
cytoplasmic tail (CY). When expressed in Chinese hamster ovary (CHO) cells, this
CD46 isoform underwent no O-glycosylation and was mostly retained in the
endoplasmic reticulum. This unusual behaviour of the new isoform was due in part
to the short TM and the unusual sequences of the CY. The molecular mass of this
isoform was 42,000, approximately 20,000 smaller than conventional CD46. These
properties of the STc/CY4 isoform were similar to those of sperm CD46. The only
difference between sperm CD46 and the STc/CY4 isoform expressed on CHO cells was
that only the latter possessed N-linked sugars of high mannose types. Since the
STc/CY4 isoform may behave like sperm CD46 in cellular localization and post
translational modification, studies of sperm-egg interassociation were performed
using hamster eggs and CHO cell clones expressing various isoforms including the
STc/CY4. Rosette formation was seen most effectively between hamster eggs and
STc/CY4-expressing CHO cells. These results infer that O-glycosylation perturbs
CD46-mediated sperm-binding to eggs and thus sperm CD46 lacking O-linked sugars
can serve as an adhesion molecule. The possible role of CD46 in fertilization and
the structural differences between sperm and conventional CD46 are discussed.
PMID- 9659229
TI - Preservation of mucosal and systemic adjuvant properties of ISCOMS in the absence
of functional interleukin-4 or interferon-gamma.
AB - Adjuvants are a critical component of non-viable vaccine vectors, particularly
for those to be used via mucosal routes. Although most adjuvants act by inducing
local inflammatory responses, the molecular basis of many of these effects is
unclear. Here we have investigated whether interleukin-4 (IL-4) and interferon
gamma (IFN-gamma) are required for the induction of local and systemic immune
responses by oral and parenteral administration of ovalbumin (OVA) in immune
stimulating complexes (ISCOMS), a potent mucosal adjuvant vector. Our results
show that after oral or systemic immunization with OVA ISCOMS, IL-4 knockout
(IL4KO) and IFN-gamma receptor knockout (IFN-gamma RKO) mice develop an entirely
normal range of immune responses including delayed-type hypersensitivity (DTH),
serum immunoglobulin G (IgG) antibodies, T-cell proliferation and cytokine
production, class I major histocompatibility complex (MHC)-restricted cytotoxic T
lymphocyte (CTL) activity and intestinal IgA antibodies. These responses were of
a similar magnitude to those found in the wild-type mice, indicating that the
immunogenicity of ISCOMS is not influenced by the presence of IL-4 or IFN-gamma
and emphasizing the potential of ISCOMS as widely applicable mucosal adjuvants.
PMID- 9659230
TI - Intranasal immunization of mice with herpes simplex virus type 2 recombinant gD2:
the effect of adjuvants on mucosal and serum antibody responses.
AB - Mucosal immunization offers the potential for inducing IgA antibody responses in
the vagina, the site of infection for many viruses, including herpes simplex type
2 (HSV-2). To investigate this possibility, mice were immunized intranasally with
10 micrograms glycoprotein D2 (gD2) from HSV combined with a series of adjuvants
of proven efficacy; the oil in water emulsion MF59, poly(D,L-lactide-co
glycolide) microparticles (PLG) (encapsulated or co-administered), immune
stimulating complexes (iscoms) (incorporated or co-administered with iscomatrix)
and the genetically detoxified enterotoxin from Escherichia coli, LT-K63.
Encapsulation of gD2 into PLG microparticles, incorporation of gD2 into iscoms
and co-administration of gD2 with LT-K63 induced mucosal IgA antibody responses
(nasal wash, saliva and vaginal wash) which were greater than those induced by
intramuscular administration of gD2 with MF59. Intranasal immunization with these
formulations also induced substantial levels of serum IgG and neutralizing
antibodies. These studies demonstrated that intranasal immunization with potent
adjuvants is an effective means to induce mucosal antibody responses, even in the
lower genital tract.
PMID- 9659231
TI - Antibodies with idiotypic and anti-idiotypic reactivity (epibodies) in
conventional immune responses to dinitrophenylated carriers.
AB - A number of monoclonal antibodies were derived from the spleen cells of
dinitropheryl (DNP)-immunized mice. Both T-dependent and T-independent carriers
were used, and the intensity and length of immunization were varied. It was found
that some of the antibodies had only idiotypic (Ab1) reactivity, while others had
both idiotypic (Ab1) and anti-idiotypic (Ab2) reactivity. Among the latter
antibodies some molecules reacted specifically with DNP and with the combining
site of anti-DNP antibodies (epibodies), while others bound DNP and anti-DNP Abs
as well as a variety of unrelated antigens (polyreactive antibodies). The
proportion of the three types of antibodies (antigen-specific, epibodies and
polyreactive antibodies) varied with the nature of the carrier, the intensity of
the immunization, and the length of the immunization process. Further
characterization of the epibodies, which were predominant in the secondary
response to DNP-keyhole limpet haemocyanin (KLH), showed that both Ab1 and Ab2
reactivities were inhibited by both soluble ligands (DNP and anti-DNP),
indicating that the specific combining site of the monoclonal antibodies (mAbs)
(and/or of the rabbit anti-DNP antibody in the case of Ab2) was involved in both
activities. Both Ab1 and Ab2 reactivities were removed by absorption of the mAbs
with either immobilized DNP or immobilized rabbit anti-DNP. The mAbs were capable
of binding themselves as well as to other mAbs with the same characteristics. The
affinity constants of several mAbs for both the DNP and anti-DNP ligands were
determined.
PMID- 9659232
TI - Characterization of the gene for the membrane and secretory form of the IgM heavy
chain constant region gene (C mu) of the cow (Bos taurus).
AB - Our present understanding of the evolution of immunoglobulins is derived from a
few vertebrate species. In order to obtain additional information on the
development of the humoral immune system, we cloned and determined the nucleotide
sequence of the bovine cDNA and genomic IgM heavy-chain constant region gene (C
mu). The gene contains four constant region domain-encoding exons (CH1 to CH4)
and two exons encoding the transmembrane domain (TM1, TM2), expressed in the
membrane-bound receptor form of the IgM. The sequence of a cDNA clone encoding
the 3' portion of the membrane form of the mu-chain revealed that the TM1 exon is
spliced to the CH4 exon, as occurs in other mammals. Comparison of deduced amino
acid sequence data from different vertebrates revealed a high similarity to sheep
C mu (88%) and a lower degree of similarity to pig (62%), rat (62%), rabbit (58%)
human (56%), hamster (55%), mouse (54%), chicken (28%) and horned shark (22%) C
mu.
PMID- 9659233
TI - Specific inhibition of immunoglobulin E-mediated allergic reaction using
antisense Fc epsilon RI alpha oligodeoxynucleotides.
AB - We have investigated the ability of an antisense immunoglobulin E (IgE) receptor
alpha-subunit oligodeoxynucleotide (Fc epsilon RI alpha ODN) specifically to
inhibit IgE-mediated allergic reactions in the mouse. Synthetic antisense Fc
epsilon RI alpha ODN dose-dependently inhibited passive cutaneous anaphylaxis and
histamine release from the mouse peritoneal mast cells (MPMC) activated by anti
dinitrophenyl (DNP) IgE. Northern blot analysis showed that the mast cells
treated with antisense Fc epsilon RI alpha ODN exhibited no detectable levels of
L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the cells
treated with sense Fc epsilon RI alpha ODN possessed significant amounts of this
mRNA. Examination of the elevation of cAMP levels in MPMC following the
activation with anti-DNP IgE demonstrated a significant rise in activated cells,
but not in the antisense Fc epsilon RI alpha ODN-treated cells. Moreover,
antisense Fc epsilon RI alpha ODN had a significant inhibitory effect on anti-DNP
IgE-induced tumour necrosis factor-alpha production. Our results demonstrated
that antisense Fc epsilon RI alpha ODN inhibited the IgE-mediated allergic
reaction in vivo and in vitro.
PMID- 9659234
TI - Activation of complement by human IgG1 and human IgG3 antibodies against the
human leucocyte antigen CD52.
AB - Activation of the complement cascade by immunoglobulin G (IgG) plays a major role
in the host defense against pathogens. Using recombinant human antibodies
specific for the leucocyte antigen CD52, different allotypes of human IgG1
subclass were compared for their ability to activate human complement. In
addition the roles of the different length hinge regions of IgG1 and IgG3 were
investigated. It was found that the naturally occurring allotypes G1m(a,z) and
G1m(f), and one artificially created isoallotype, G1m(null), did not
significantly differ in their overall ability to cause cell lysis. However, some
differences in binding of individual components of the classical activation
pathway were detected. More of the complement component C1s seemed to be
associated with the allotype G1m(f), although this did not result in an overall
improvement in lytic potency. In this system the wild-type IgG3 was found to be
less effective in complement lysis than IgG1. By shortening the hinge region of
IgG3 to resemble that of an IgG1 antibody, increased complement binding was
observed compared with that of wild-type IgG3 and the IgG1 allotypes. The overall
lytic potency of the antibody was also improved compared with wild type IgG3 and
it was also slightly more effective than the IgG1 allotypes.
PMID- 9659235
TI - Imaging bioluminescent indicators shows Ca2+ and ATP permeability thresholds in
live cells attacked by complement.
AB - A series of permeability thresholds to Ca2+ metabolites and macromolecules,
occurring at different times when cells are attacked by complement, has been
established by imaging HeLa cells transiently expressing a recombinant cytosolic
fusion protein of firefly luciferase and aequorin (luciferase-aequorin) to
measure changes in ATP and cytosolic free Ca2+. Nuclear fluorescence of propidium
was used as a measure of permeability to small molecules, and luciferase activity
imaged to assess lysis. The rise in cytosolic free Ca2+ observed after C9 attack
preceded by at least 60 s both the increase in propidium fluorescence, measured
in single cells, and the decrease in ATP monitored by luciferase light emission.
These effects were dependent on the concentration of C9. At concentrations of C9
up to 4 micrograms/ml no loss of luciferase-aequorin protein was detected at the
end of the experiment. Thus the membrane integrity of the cells remained intact,
even though the cells were permeable to propidium. These results confirmed our
earlier observations that propidium permeability in cells attacked by complement
was not a reliable measure of cell death. They also show that it is vital to take
account of cellular heterogeneity if the mechanisms by which cells respond to
membrane pore former attack are to be correctly interpreted.
PMID- 9659236
TI - Prion diseases: what will be next?
PMID- 9659237
TI - Application of molecular typing to the epidemiology of Streptococcus pneumoniae.
AB - The spread of antibiotic resistance and the development of new vaccines have
focused attention on the epidemiology of Streptococcus pneumoniae over recent
years. While serotyping and the determination of antibiotic resistance remain
primary methods for characterising pneumococci, molecular typing can add greater
discrimination and complementary information. Methods based on restriction
fragment length polymorphism within total DNA or non-specific polymerase chain
reaction provide information representative of the whole genome and can be used
to recognise closely related isolates from different sources, whether in the
investigation of possible cross infection at the local level or in the
investigation of national or international spread of antibiotic resistant
strains. Fingerprinting of penicillin binding protein genes adds further
information in the analysis of penicillin resistant isolates. The use of a
combination of typing methods to analyse both the genome as a whole and specific
loci has led to the realisation that pneumococci undergo horizontal gene transfer
much more often than most other bacterial species. In particular the spread of
penicillin resistance has been characterised by a combination of the spread of
epidemic strains, transfer of chromosomal resistance genes from such strains into
other genetic backgrounds, and transfer of capsule genes resulting in the switch
of serotypes within strains. In the future molecular typing will have an
important role in discovering whether widespread vaccination leads to genetic
modification of the pneumococcal population causing invasive disease.
PMID- 9659238
TI - The importance of "like to like" ISI calibrations with freeze dried plasmas.
European Concerted Action on Anticoagulation.
AB - AIM: To assess reliability of like to like and cross species calibrations using
two types of certified freeze dried plasma calibrants--artificially depleted of
vitamin K clotting factors, and from coumarin treated patients. METHODS: Six ECAA
national control laboratories provided certified values for the freeze dried
plasmas in terms of the human plain international reference preparation (IRP)
(BCT/441) with the manual prothrombin time technique. Eight other ECAA national
laboratories determined international sensitivity index (ISI) values in full
fresh plasma same species and cross species WHO calibrations against a low ISI
human IRP (BCT/441) of the ECAA low ISI human thromboplastin and high ISI ECAA
rabbit thromboplastin. Parallel calibrations were performed using the certified
values. RESULTS: Calibrations on fresh plasmas of the human ECAA reference
thromboplastin (stated ISI = 0.95) gave ISI of 0.957 against the human IRP and
1.66 against the rabbit IRP. The ECAA rabbit (stated ISI = 1.67) gave an
identical value on the fresh plasma calibration v the human IRP. With freeze
dried depleted plasmas certified in terms of the human IRP, the ISI of the ECAA
human was 1.01, but the ECAA rabbit (stated ISI = 1.67) gave a low ISI of 1.47.
The freeze dried coumarin plasmas gave an ISI of 0.943 for the ECAA human but
only 1.493 for the ECAA rabbit. CONCLUSIONS: Fresh plasmas give reliable ISI when
calibrating thromboplastins in same species and cross species calibrations.
Freeze dried plasmas certified in terms of a single IRP, whether artificially
depleted or of coumarin plasma origin, cannot be used for calibration of
dissimilar thromboplastins.
PMID- 9659239
TI - Ticlopidine induced colitis: a histopathological study including apoptosis.
AB - AIMS: To describe ticlopidine related microscopic colitis and to assess the
occurrence of apoptosis in the colon epithelium. METHODS: A series of colorectal
biopsy samples from nine patients with ticlopidine related chronic diarrhoea were
analysed. Biopsies were also taken from five of these patients between two and
four months after ticlopidine withdrawal. The number of apoptotic cells in the
crypts/mm2 (apoptotic index) was calculated using in situ labelling by terminal
deoxyribonucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling
(TUNEL). All specimens were matched to normal colorectal specimens from a control
group of comparable age and sex distribution. RESULTS: Histological examination
of the colon biopsy specimens taken from all nine patients with ticlopidine
related chronic diarrhoea showed characteristic features of microscopic colitis.
The histology returned to normal when ticlopidine was withdrawn. Apoptotic cells
were rarely found in controls, and the mean apoptotic index was 0.53. The
apoptotic index was significantly higher (16.53) in ticlopidine related colitis,
but decreased dramatically to control value when ticlopidine was withdrawn.
CONCLUSION: Microscopic colitis can be induced by ticlopidine and is accompanied
by an increase in epithelial apoptosis. Hence, increased apoptosis might be
related to drug injury or might be part of microscopic colitis.
PMID- 9659240
TI - Telomerase expression shows differences across multiple regions of
oligodendroglioma versus high grade astrocytomas but shows correlation with Mib-1
labelling.
AB - AIMS/BACKGROUND: Telomerase is an enzyme that is expressed in most human
neoplasms and is associated with tumour immortality. Determination of the point
in neoplastic transformation at which telomerase is expressed may aid the
understanding of tumour pathogenesis and progression. Despite numerous reports on
telomerase, few studies have investigated its expression in high grade glial
tumours. These studies, performed on archival banked, single brain tumour
specimens, have shown conflicting results for oligodendrogliomas and unexpectedly
negative results for telomerase expression in high grade astrocytomas, with one
third to one half of glioblastoma multiformes being negative. METHODS: 34 rapidly
banked glioma specimens taken from patients undergoing gross total surgical
resection of their tumours were studied. Telomerase expression was assessed
across 3-8 sampled regions from each tumour by the telomeric repeat amplification
protocol (TRAP) assay. Matched mirror image tissue samples were taken for
histological analysis of tissue adequacy, statistical correlation of telomerase
with tumour histological features, Mib-1 (a marker for cell cycling) labelling,
and p53 immunohistochemistry. RESULTS: All five well differentiated
oligodendrogliomas were homogeneously telomerase negative and two of three
untreated anaplastic oligodendrogliomas were homogeneously positive. In contrast,
10 of 14 high grade astrocytomas showed heterogeneity for telomerase expression
across the multiple regions sampled. All glioblastoma multiformes and two of
three anaplastic astrocytomas showed at least one region positive for telomerase.
When test samples were individually assessed in both oligodendrogliomas and high
grade astrocytomas, telomerase expression was associated with Mib-1 labelling (p
< 0.001). For the entire group, telomerase expression was associated with grade
of tumour, age of patient, and vascular endothelial proliferation (all p <
0.001). CONCLUSIONS: This regional study clarifies that all glioblastoma
multiformes are at least focally positive and that telomerase expression
correlates with tumour grade in oligodendrogliomas. Homogeneity versus
heterogeneity for telomerase expression across multiple regions of
oligodendrogliomas versus high grade astrocytomas may provide important
preclinical data on the use of antitelomerase agents in these adult glial
tumours.
PMID- 9659241
TI - Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and
cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer.
AB - AIMS: To analyse the allele frequencies of DNA polymorphisms at the genes for
cytochromes P450IIE1 and P450IID6, N-acetyltransferase-2, and glutathione S
transferase-M1 in patients with head and neck squamous cell carcinoma, in an
attempt to define genetic factors involved in the susceptibility to this cancer,
which is strongly associated with tobacco consumption. METHODS: Determination of
restriction fragment length polymorphism (RFLP) at cytochromes P450IIE1/P450IID6
and NAT2 genes, and the presence of homozygous deletion of the GSTM1 gene, in 200
controls and 75 head and neck cancer patients. Allelic frequencies between the
two groups were compared using a chi 2 test, and odds ratio with 95% confidence
intervals were calculated. RESULTS: There was no evidence of an association
between alleles of CYP2D6 and CYP2E1 and head and neck cancer in our population.
Similarly, frequencies of individuals lacking the GSTM1 gene did not differ
between controls and patients. However, individuals with the NAT2-SA phenotype
were at higher risk of developing head and neck cancer. The frequencies of the
most common SA genotype (homozygous for the NAT2*5 allele) were higher in
patients than in controls (27% v 15%, respectively). Slow acetylators homozygous
for the NAT2*6 allele, the second most common SA allele, were also more common in
patients than in controls (11% v 5%, respectively). CONCLUSIONS: Slow NAT2
activity is a risk factor possibly leading to the development of head and neck
cancer in response to tobacco carcinogens.
PMID- 9659242
TI - Evaluation of Helicobacter pylori vacA genotype in Japanese patients with gastric
cancer.
AB - AIM: To examine the vacA genotypes of Helicobacter pylori strains in Japan and to
define whether any specific genotype was associated with gastric cancer. METHODS:
The allelic variation of vacA gene was studied using a recently introduced
polymerase chain reaction based vacA genotyping system. RESULTS: 80 H pylori
strains were isolated from gastric biopsies of 40 patients with gastric cancer
and 40 control subjects in a Japanese population. All strains were s1/m1 subtype
and 79 of 80 strains were classified as s1a subtype. CONCLUSIONS: The recently
proposed vacA genotyping system is applicable to Japanese H pylori strains and
most strains have the s1a genotype, associated with increased virulence. While
the high frequency of s1a/m1 vacA genotype might play a role in the increased
incidence of atrophic gastritis and gastric cancer in Japanese subjects, it
precludes its use as a predictor of clinical outcome of H pylori infection in
Japan.
PMID- 9659243
TI - Experience of changing between signal and Bactec 9240 blood culture systems in a
children's hospital.
AB - AIM: To compare experience of positive blood cultures in successive years before
and after changing from Signal (Unipath) to Bactec 9240 (Becton Dickinson) blood
culture systems. METHODS: Analysis of data collected prospectively on 7967 Signal
and 7062 Bactec blood culture sets. RESULTS: Significant growths occurred in 5.7%
of Signal and 8.9% of Bactec cultures; 33.0% more significant isolates and 24.0%
more episodes of bacteraemia were detected in the second year, following
introduction of the Bactec system. Inpatient hospital activity increased by 8.2%
between the first and second years, although the numbers of blood cultures
received actually fell by 11.4%. There were striking increases in numbers of
isolates of coagulase negative staphylococci (47.7%) and Enterobacteriaceae
(56.8%) from Bactec cultures. Two anaerobic bacteraemias were detected in Signal
blood cultures, whereas none was detected by the Bactec system, despite 12.1% of
sets including an anaerobic bottle. Of significant positive cultures, 90.2% were
detected within one day with the Bactec 9240, compared with only 50.0% of Signal
cultures; 20.7% of significant positive Signal blood cultures were detected only
on terminal subculture. Microorganisms that were not significant were isolated
from 5.1% Signal and 3.8% Bactec cultures. CONCLUSIONS: Compared with the Signal
system, the Bactec 9240 offers markedly more rapid and sensitive detection of
bacteraemia, together with a lower rate of non-significant isolates. However,
using a single PEDS PLUS/F bottle the few episodes of anaerobic bacteraemia that
occur in children are likely to be missed.
PMID- 9659244
TI - The inhibitory effect of phosphate on the ligase chain reaction used for
detecting Chlamydia trachomatis.
AB - AIMS: To examine the detection limit of the ligase chain reaction kit for
Chlamydia trachomatis, to study the inhibitory effect of phosphate on the ligase
chain reaction, and to clarify the mechanism of inhibition. METHODS: Three
reference serovars of C trachomatis--D/UW-3/Cx, F/UW-6/Cx, and L2/434/Bu--were
used to test the sensitivity of the chlamydia ligase chain reaction. Comparison
was made of the inhibition by phosphate before and after DNA amplification.
Phosphate in up to 2.4 mM concentration was added to specimens of C trachomatis
serovar D (1 to 50 inclusion forming units (IFU)/reaction) before DNA
amplification to examine the concentration dependency of phosphate inhibition of
the ligase chain reaction. RESULTS: The detection limits were 0.6 IFU/reaction
for serovar D/UW-3/Cx and F/UW-6/Cx, and 0.4 IFU/reaction for L2/434/Bu.
Phosphate inhibited the ligase chain reaction only when it was added before the
amplification stage. The specimens containing chlamydia at 1 to 50 IFU/reaction
were negative when the concentration of phosphate added at the prethermocycle
stage was more than 1.2 mM. CONCLUSIONS: Ligase chain reaction analysis is a
reliable method of diagnosing C trachomatis infection because of its high
sensitivity. It would be clearly superior to the currently used methods if the
problem of inhibitors could be eliminated. The mechanism of inhibition of the
ligase chain reaction by phosphate was thought to be blockade of the
amplification of the target DNA. The efficacy of the ligase chain reaction could
be inhibited by phosphate in the urine, so duplicate dilution analysis of some
negative specimens should be useful.
PMID- 9659245
TI - Comparison of throat swabs with sputum specimens for the detection of Chlamydia
pneumoniae antigen by direct immunofluorescence.
AB - AIM: To compare throat swabs with sputum specimens for Chlamydia pneumoniae
antigen detection. METHODS: During a one year period, sputum and throat swabs
from 50 patients over 15 years of age with acute or persisting lower respiratory
tract infection were examined for C pneumoniae antigen by direct
immunofluorescence. RESULTS: C pneumoniae antigen was detected in 18/50 patients
(36.0%) from sputum, throat swab, or both. Paired sputum and throat swabs were
received from 35/50 patients (70.0%). C pneumoniae antigen was detected in either
or both specimens from 14/35 patients (40.0%). Of the 14 positive patients, both
specimens were positive in nine (64.3%), throat swab only in four (28.6%), and
sputum only in one (7.1%). Of the remaining 15 patients from whom only a single
specimen was sent, a further three of eight throat swabs and one of seven sputum
specimens were positive. There was no statistically significant difference
between the results obtained from the two types of specimen. CONCLUSIONS: Throat
swabs may be as good as sputum for the detection of C pneumoniae antigen.
PMID- 9659247
TI - The Vitek analyser for routine bacterial identification and susceptibility
testing: protocols, problems, and pitfalls.
AB - Automated and semiautomated technology in microbiology has seen great advances in
recent years. The choice of automated equipment for the identification and
susceptibility testing of bacteria in a routine diagnostic laboratory depends on
speed, accuracy, ease of use, and cost factors. The Vitek analyser (bioMerieux,
UK) was installed in a busy diagnostic teaching hospital laboratory in London.
This report describes one year's experience. Changes to work practice as a result
of incorporating the equipment into the laboratory, and the advantages and
disadvantages of automation in key areas are described in detail, together with
possible solutions to problems. The Vitek analyser was found to be valuable for
the speed and accuracy with which results were available for the common bacterial
pathogens. Results of susceptibility testing were standardised according to NCCLS
guidelines and used breakpoint MICs to ascertain susceptibility and resistance;
they were an improvement on disc testing. This equipment is not a reference
facility for difficult to identify organisms and many manual techniques,
including some disc susceptibility testing, will have to be retained by the
laboratory.
PMID- 9659246
TI - Do IgA, IgE, and IgG avidity tests have any value in the diagnosis of toxoplasma
infection in pregnancy?
AB - AIM: To determine the value of tests for specific IgA, IgE, and IgG avidity in
diagnosing Toxoplasma gondii infection during pregnancy. METHODS: In a
retrospective study, current serological tests (dye test and three IgM assays
with different sensitivities) were compared with immunosorbent agglutination
assays (ISAGA) for specific IgA and IgE and an IgG avidity enzyme linked
immunosorbent assay (ELISA). Patient group 1 comprised six women with definite or
probable infection during pregnancy determined by congenital toxoplasmosis or
laboratory results. Group 2 comprised seven women infected during or before 11
pregnancies (two consecutive pregnancies in two patients and three in a third).
RESULTS: One patient in group 1 seroconverted during pregnancy. IgA ISAGA and
avidity confirmed acute infection when confirmatory IgM ELISA remained negative.
In five of six patients from group 1, IgA and IgE ISAGA and avidity confirmed
acute infection. In group 2, the dye test titre was raised in seven of 11
pregnancies (six of seven patients). Specific IgM and IgA were positive during
all 11 pregnancies. IgE ISAGA was positive in only four of 11 pregnancies (three
of seven patients), but negative results in the remainder may exclude acute
infection. High avidity antibodies indicative of past infection were found in
four of 11 pregnancies (two of seven patients). CONCLUSIONS: Each test improved
diagnosis or timing of infection but no single test was ideal. The IgA ISAGA was
sensitive and detected seroconversion. Positive IgE ISAGA and low avidity both
confirmed infection, whereas negative IgE may exclude acute infection. High
avidity diagnosed past infection but persistence of low avidity reduced its value
to differentiate acute and past infection. Further studies with larger patient
groups are needed to determine the optimum diagnostic strategy. These techniques
are valuable in complementing existing tests.
PMID- 9659248
TI - Apolipoprotein E alleles in women with severe pre-eclampsia.
AB - This study investigated the frequency of apolipoprotein E (apoE) alleles among
women with severe pre-eclampsia. The presence of the three most common apoE
alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain
reaction-restriction fragment length polymorphism in three groups of white women:
non-pregnant healthy (n = 101), pregnant healthy (n = 52), and pregnant with a
diagnosis of severe pre-eclampsia (n = 54). The frequency of apo epsilon 2 was
highest among women with severe pre-eclampsia (16.6%) followed by non-pregnant
women (12.9%), and those experiencing a healthy pregnancy (10.6%). The higher
frequency of the apo epsilon 2 allele detected among women with severe pre
eclampsia suggests that apoE may play a role in the development of pre-eclampsia.
PMID- 9659250
TI - Pathologists dislike sound? Evaluation of a computerised training microscope.
AB - AIM: To evaluate the use of multimedia enhancements, using a computerised
microscope, in the training of microscope skills. METHODS: The HOME microscope
provides facilities to highlight features of interest in conjunction with either
text display or aural presentation. A pilot study was carried out with 10
individuals, eight of whom were at different stages of pathology training. A
tutorial was implemented employing sound or text, and each individual tested each
version. Both the subjective impressions of users and objective measurement of
their patterns of use were recorded. RESULTS: Although both versions improved
learning, users took longer to work through the aural than the text version; 90%
of users preferred the text only version, including all eight individuals
involved in pathology training. CONCLUSIONS: Pathologists appear to prefer visual
rather than aural input when using teaching systems such as the HOME microscope
and sound does not give added value to the training experience.
PMID- 9659249
TI - A method for the confirmation and identification of drugs of misuse in urine
using solid phase extraction and gas-liquid chromatography with mass
spectrometry.
AB - A method is described for the confirmation/identification of a range of commonly
misused drugs in urine samples. The method has been used for two years without
problems for a range of purposes including hospital/clinic drugs of misuse
screening and for toxicology in coroner's cases. Urine samples which have given a
positive result on immunochemical screening for a particular drug group or groups
(for example, opiates) can be processed with identification of the drugs present
using a single procedure. Bond ElutCertify columns are used for the extraction of
drugs from the samples followed by propionylation and gas chromatography with
mass selective detection.
PMID- 9659251
TI - Spontaneous regression of renal cell carcinoma: a pitfall in diagnosis of renal
lesions.
AB - Two cases of renal cell carcinoma, both of which underwent extensive spontaneous
regression, are reported. The first occurred in a 56 year old man, forming a well
circumscribed renal cortical nodule which contained only very occasional foci of
viable renal cell carcinoma with areas of hyalinisation and calcification, and
with metaplastic ossification. The second lesion was removed from an 82 year old
man, comprising a cystic cavity containing necrotic debris with only occasional
viable foci of classical renal cell carcinoma. Spontaneous regres